通过练习学习

有机反应机理
福山 透

有机合成化学协会編

三氢剑魔 翻译
演習で学ぶ有機反応機構

化学同人
 序 言

作为学会的事业之一，有机合成化学协会从以前就开始工作于手册和书本出版的
事情了。不过,近年来由于出版界的情况变了很多。于是,本协会决定从新时代出发，
开始一次新的出版活动。在2004年时组成出版委员会后,一部分委员商讨了今后的出版
企划。

虽然当代在学术和研究这方面上，世界上已经充斥了大量的研究有关信息,并且它
们整理的各种著作物出版了很多，但是, 这相比很久以前，世人对于出版事情上心思
状况有很大的变化,于是这就导致了信息泛滥。同时由于计算机技术蓬勃发展，信息处
理这方面开始变得简单化,特别是网络搜索这方面，与以前相比,个人获取新的信息和
必要的数据也变得十分便捷。在这样的大环境下,不得不承认，今天的出版物的利用价
值开始逐渐缩水。

在这种风潮中,有机合成化学协会必须为了推进出版业的发展，做出一本书作为参
照。本协会的会员需要在书中引入了各种令人生趣的内容，并且尽可能选择出有益的
信息，用于制作题目,最后与类似的出版物达成一致,才能提出许多崭新的内容和企划
的建议。从这样的思路出发,出版委员会为之进行了努力。

这次出版的是第一册是东京大学研究生院药学研究系科的福山透教授的研究室企
划编写的《通过练习学习有机反应机理》，并即将被出版。它是福山研究室在长期收
集了很多资料后,用于理解有机合成反应和反应机理思考能力的练习用书。这本书,它
通过完整的总结编辑,新颖的练习和相当风致的豁达的独特内容，使有机有机合成化学
专业的学生在阅读过程中妙趣横生。另外鸣谢有关的有机合成的研究人员，尽自己的
所能为本协会的书目出版出一份力。

2005 年 7 月

出版委员会委员长

辻 二郎
 有机合成化学协会 出版委员会

【出版委员长】 辻 二郎 （东京工业大学名誉教授）
【出版副委员长】 竜田邦明 （早稻田大学理工学術院院长）

【出版委员】 户嵨一敦 （慶應義塾大学理工学部教授）

德山英利 （東京大学大学院薬学系研究科助教授）

编 写 者

福山 透 （东京大学药学系研究科教授）
德山英利 （东京大学药学系研究科副教授）
菅 敏幸 （静冈县立大学药学部教授）
横島 聡 （东京大学药学系研究科助手）

赤岩路則 北 陽一 半矢佑己
阿部昌尚 小泉一二三 松本幸爾
磯村峰孝 小柴隆宏 三村 晵
井上 畅 小村英樹 宫崎 徹
内田賢司 佐藤 步 森元後晴
岡野健太郎 下川 淳 山岸尋亮

三氢剑魔 翻译
 前 言

自从医学、农学的开发后,科技产生了很大的发展，各种创新应有尽有,有机合成
化学的重要性也逐渐增大,这也成为了新反应和新化合物相关的论文在学术杂志上泛滥
的主要原因。19世纪以来，各种方面的信息积累产生了名为“有机化学”的宽阔的大
海,而我们为了达到目标目的地，掌握出色的航海术,很有必要。当然,把繁综错杂的有
机反应,一个一个背过的需要天价的时间,很没有效率。

近年来,由于计算化学的发展, 我们轻视了基于有机电子论形式上的反应机理分析
的重要性。但是,掌握了电子论的话,可以将各种各样的反应统一理解成为可能。反应
途径的预测和反应方式,反应的设计，可以使我们对于反应的方式有更好的理解。如果
只是一味的死记硬背的庞大的已知反应，那么就不会有什么新的发现。而掌握反应时
电子的流动方向，就是掌握了有机反应的活力源泉。有机电子论,即所谓的“arrow-
pushing mechanism”,就是考虑反应中化学键的稳定性以及他们的生成与开裂，通过
能量结合，引导其产生出一个有利的生成物的途径的学问。对于初学者来说尤其重要
的是,从整个分子来观察,绝对不可以省略的反应中的每一步。然后仔细、深入的观察
接下来会发生什么反应。大多数有机化学教科书中,取录的概念和领域太多,导致了实
际上个别的反应的解说很不充分。另外,对于基本反应们的高级的反应机理的详细解说
的练习书，也少。

在美国很多大学的有机化学专业研究生每月都要参加一个名为“Cumulative
Examination”的测试,到达一定的合格分数后可以提早获得博士学位资格。

测试中有机反应机理的问题题目很多,所以他们都在自己进行有机电子论学习。另
一方面,在我国,学院和研究生院的专门教育相比没有美国的大学要求严格，是其所属
研究室对于学生教育的大部分责任。而这样的现状的基础上，为了发挥有机化学的力
量,为了更好的进行讲座,笔记，教科书以及学习参考书的学习, 相信你在通过这本书
的捷径，自学并练习了书写各种各样的重要反应，从而更加彻底的理解自己学习的东
西。

这本书是由初级问题(a),中级问题(b), 高级问题(c)和解答篇组成的。A是基础重
要的反应问题,B是研究生院的考试题,这比A组题难度要高。而C则是从研究生院的研究
人员收集的各种世界上的研究问题。
 A组题对于初学者来说，完全可以很轻松地自主挑战的。初级篇是参考于反应的简
单的步骤省略。另外,倘若一个问题20分钟也考虑不明白的话，还是乖乖自己翻答案比
较好，不懂的题目还可以等到以后再挑战。为此我们特地将问题分类，各种问题分为
三个阶段，为能力提高做准备。答案栏写的反应机理同时也著名了引用文献的作者,不
仅是福山研究室所考虑到的东西,也有与出版社双方考虑的因素。

一般来说,有机反应中不稳定的中间体很难确认,从而导致反应途径中有许多盲
区。因此,考虑真正的反应机构到底是什么是什么叫我们很是头疼。不过从逻辑上考
虑，还是反应机理更为重要。这本书的问题如果可以全部变成自己的东西。拥有相当
有机化学的实力不是问题。另外。答案栏的评语是用英语书写的，这种程度的英语对
于初学者来说不算什么问题,而对于英语简写，后文也有说明。

本考试中刊载的大部分问题,是当时研究室的团队会议出题。工作人员选择的问
题,是文部科学省的特定领域的研究“生物功能分子的创制”计划班的班成员承蒙提
供的问题，在这里对其表示感谢了。另外,这本书之前的显示的那几页是当时实验室
的工作人员和研究生百忙之余中执笔的,特别要感谢横岛聡助手的忘我的努力。

最后,这本书的企划、制作帮助您的化学同人编辑部平佑幸深深地对您表示感谢。

2005年7月东京大学研究生院药学研究科

天然物合成化学研究室福山透
 目 录

● 序言
● 出版委员会名单与编者名单
● 前言
● 缩写表

问 题
■ 初级編
初级编，由有机化学的教科书中摘录而成
【例 題】2
問题数 78 題
■ 中级編
中级编，研究生入学考试上要求的题目
【例 題】20
問题数 128 題
■ 上级編
上级编，历史上著名的反应

【例 題】48

問题数 109 題
答 案

答案 初级編
答案 中级編
答案 上级編

【专 栏】福山研究室的小组会议的景象
机理书写问题的解决方案
【附 录】有机反应的反应机理的考虑方法
电负性和酸度常数
【索 引】日本及欧美的书籍引用目录
 缩 写 表

△ 加热 liq 液体
Ac 乙酰基 m 间位
acac 乙酰丙酮基 mCPBA 间氯过氧苯甲酸
AIBN 偶氮二异丁腈 Me 甲基
aq 水溶液 MEM 2-甲氧基乙氧基甲基氯
Ar 芳基 MOM 甲氧甲基
Bn 苯甲基 Ms 甲磺酰基
Boc 叔丁氧羰基 MS 分子筛
Bu 正丁基 n 正-（某基）
cat 催化 NBS N-溴代丁二酰亚胺
Cbz 苯甲氧羰基 NCS N-氯代丁二酰亚胺
CSA 樟脑磺酸 NMM N-甲基吗啡啉
CSI 磺酰氯异氰酸酯 NMO N-甲基-N-氧化吗啉
Cy 环己基 Ns 邻（对）硝基苯磺酰基
DABCO 1,4-二氮杂双环[2.2.2]辛烷 o 邻位
dba 己二酸二丁酯 p 对位
DBU 二环[4.3.0]-1,5-二氮-5-十一烯 Ph 苯基
DCC N,N'-二环己基碳二亚胺 Pr 丙基
DDQ 2,3-二氯-5,6-二氰-1,4-苯醌 rt 室温
DEAD 偶氮二甲酸二乙酯 s 仲-（某基）
DMAP 4-二甲氨基吡啶 SET 单电子转移
DME 二甲醚 t 叔-（某基）
DMF 二甲基甲酰胺 TBAF 四丁基氟化铵
DMSO 二甲亚砜 TBS 叔丁基二甲基硅烷基
Tf 三氟甲磺酸基
dppb 1,4-双(二苯基膦)丁烷 TFA 三氟乙酸
DPPE 双(二苯基膦基)乙烷 TFAA 三氟乙酸酐
EDCI 1-乙基-(3-二甲基氨基丙基)碳 TfOH 三氟甲磺酸
酰二亚胺 THF 四氢呋喃
eq 等量物质 TIPS 三异丙基甲硅烷基
Et 乙基 TMS 三甲基硅烷基
HMPA 六甲基磷酸胺 tol 苯甲基
hv 光照 TosMIC 对甲基苯磺酰甲基异腈
i 异-（某基） Tr 三苯基
KHMDS 六甲基二硅基胺基钾 Ts 对甲苯磺酰基
LDA 二异丙基氨基锂 TsOH 对甲苯磺酸
问题 初级编

初级篇是以初学者的有机化学教科书中所提到的基础反应为
主要成分。初学者需要根据教科书，每个人用手画出反应的
箭头的同时，学习有机反应的想法的基础。即使是秒杀C组题
的高手,乍看这样简单的东西也会有很多问题。请用心地将氢
原子、电子这种细节统统画上,这是你能够充分理解并解开更
难解决的问题的准备运动。
例 题 写出合理的反应机理

O O
NaCN (cat)
H
EtOH-H2O
reflux OH

解 答
芳香醛偶联缩合
O
H
H
O O

CN CN

O
H
O OH
CN
CN

OH

H
CN
O O

OH

Adams, R; Marvel, C. S. Org. Synth., Coll. Vol. Ⅰ 1941, 94

问 題 写出合理的反应机理
Check Box

A001
O NaOH O
O2N H2O, reflux O2N
OMe OH
aq HCl

A002
O O
H2SO4(cat)
OH OEt
EtOH
reflux

A003
O SOCl2 O

Me OH Me Cl

A004
PhMgBr (2 eq)
Et2O
O 0oC to rt Ph Ph
Me OEt aq NH4Cl Me OH

A005
PhMgBr
Et2O
O
0oC to rt
MeO CN MeO
Ph
aq H2SO4

A006
O
Me
H N
Me O
MgBr (DMF)
H
Et2O
0oC to rt
aq HCl
 Check Box
A007

N C N

(DCC)
Me
O N N O Me
Me
Me
OH O Me
(DMAP)
EtO EtO
Me
O O
Me OH
Me
CH2Cl2, rt

A008
O
O O
OH (TsOH, cat)
+ HO
benzene
reflux

A009
O OMe
(TsOH, cat)
H OMe
HC(OMe)3
BnO MeOH BnO
OH reflux OH

A010
Br2
O O HBr, (cat) O O
Br
o
0 C

A011
NaCN, NH4Cl
Et2O-H2O
O 0oC to rt H3N CO2H
Me H aq HCl Me H
reflux
 Check Box
A012
DMF, POCl3 O
0oC then H

Me2N H2O Me2N

A013
O (HCHO)n O
Me2NH, HCl
Me NMe2
EtOH
reflux

A014
1) NH2OH-HCl
O NaOH
MeO Et2O-H2O, rt MeO CN
H
2) Ac2O, reflux
MeO MeO

A015
PCl5
N OH Et2O, 5oC O

H2O NC H
OMe

A016
MeMgBr
EtO O Et2O, -40oC O Me

aq H2SO4

A017
Me H2NNH2 Me
O K2CO3
Me Me
triethlene glycol
Me Me Me Me
reflux
 Check Box

A018

O N
CO2Et H CO2Et
H +
CO2Et benzene CO2Et
reflux

A019

O 1) NaOAc
O
Ac2O, reflux
OH H
Me N + OH
H 2) H2O, acetone HN
O
reflux O
Me O

A020
O O O
NaOH
Me H
+ EtOH-H2O
rt

A021
NaH
DMSO, rt
CO2Et
H3O+ O
CO2Et
CO2Et

A022

1)
N
H
O benzene O O
reflux
Me
2) Ac2O
dioxane, rt;
H2O, reflux
 Check Box

A023
Me
1) Br
(1.02 eq)
n-BuONa (1.0 eq)
CO2Et n-BuOH, reflux

EtO2C HO2C Me
aq KOH, reflux; aq HCl
2) heat, 180oC

A024
O O
Br2
Br
Me
AcOH
Br 20oC Br

A025
Br2, PCl3
OH OH
70 oC
Me O Me O
H2O
Br

A026
O O
Me I2 (3eq) OH
Me Me
pyridine, ;
Me H Me H
NaOH
H H EtOH-H2O H H
H3O+
HO HO

A027

Br2
O OEt
EtOH Br
O Me OEt
10oC
 Check Box
A028
1) BH3-THF (0.33 eq)
THF, rt
Me Me OH
2) NaOH
aq H2O2, rt

A029
OAc O3, CH2Cl2 OAc
-78 oC;
C10H21 OHC C10H21
Me2S, rt
OBn OBn

A030
Me

Me
HO OH H2SO4 Me O O Me

O O Et2O, rt Me Me O O Me Me

A031
Hg(OAc)2
Me Et2O-H2O, rt; OH
Me
NaBH4
aq NaOH, rt

A032
Hg(OTf )2 (1 mol%)
H2O O

MeCN-CH2Cl2 Me
rt

A033
CHO
1) MeO
I
MeO NH2 MgSO4, CH2Cl2, rt NH
MeO
2) CF3CO2H, benzene I
MeO
reflux
 Check Box
A034

MeO POCl3 MeO

HN Me toluene N
MeO reflux MeO
O Me

A035
OH OH OH
aq NaOH CHO
o
+
CHCl3, 60 C

CHO

A036
Cl H2C CH2 , AlCl3 O

O CH2Cl2
MeO -78 oC to rt MeO

A037
HCl, NaNO2 NMe2
NH2 H2O, 0 oC
N
PhNMe2 N
CO2H
0 oC CO2H

A038

Me Na, liq NH3 Me

EtOH, Et2O
Me -78 oC Me

A039
1) Na, liq NH3
THF, -78 oC
OMe C7H15Br O
CO2H -78 oC to rt C7H15
2) aq HCl
ClCH2CH2Cl
reflux
 Check Box
A040
MeO2C CO2Me
NO2 NaH NO2
THF CO2Me
F 0 to 60 oC
CO2Me

A041
Me PBr3 Me
OH Br
Me 0 oC to rt Me

A042
OH CrO3, H2SO4 O
acetone-H2O
rt

A043

O (COCl)2
A
S CH2Cl2
Me Me
-50 oC
Me A Me H
o
CH2Cl2, -50 C;
OH O
Et3N
-50 oC to rt
Me Me Me Me

A044
NaIO4
O OH aq NaHCO3 O
O O
2
CH2Cl2 CHO
O
OH O rt

A045
O EtO2C N NCO2Et O Me
Me Ph3P
OH + O CO2Et
HO CO2Et Benzene
rt
 Check Box
A046
Me
Br Me aq H2SO4
OH Me
reflux
Br

A047
HO aq H2SO4

OH reflux
O

A048
Me
Me H2SO4
Me
rt
O Me
OH

A049
Me conc H2SO4 Me

OH PhCN O
Me 5 Co Me
OH N Ph
Me Me
A050
Me Me
NC N N CN
Me Me
O (AIBN , cat) O
H n-Bu3SnH H

benzene
reflux
H H
Br

A051
HO 1) NaH, THF, ;
H H
CS2; MeI

2) n-Bu3SnH, AIBN
N toluene, reflux N
H H
Ph O Ph O
 Check Box
A052
O

1) NH

O
K2CO3, reflux
Cl H2N
2) H2NNH2, MeOH
reflux

A053

1) HCHO, HCO2H
NH2 H2O, reflux

2) aq H2O2
MeOH
3) heat 160 oC

A054

O
O Cl
O H O O
(mCPBA)
O
CH2Cl2
rt

A055
OH O
N
85% H2SO4
HN

A056
O aq H2O2
NaOH OH
H
H2O, 50 oC
OH OH
 Check Box
A057
O NaOCl
MeO NaOH MeO NH2
NH2
H2O
MeO 50 oC MeO

A058
1) ClCO2Et, Et3N
O acetone, 0 oC; O
C
Ph NaN3, H2O Ph N
OH
2) toluene
reflux

A059
Me O Me CO2H
hv
Me H N2 Me H
dioxane
H H Et2O-H2O H H
HO HO

A060
O O OMe
Cl NaOMe
Et2O
reflux

A061
1) CHBr3, t-BuOK
pentane
-15 oC to rt
A
2) MeLi
Et2O, -40 oC

A062
1) Br
OH K2CO3 OH
OMe acetone, reflux OMe
2) heat, reflux
 Check Box
A063

O TsOH (cat)
O
O toluene,

A064
e CO2Me
O M O2C CO2Me
o
O 200 C
CO2Me

A065
1) PhNHOH
EtOH, rt O
CHO Ph N Ph
2) PhHC CH2
60 oC Ph

A066
O
630 oC O
Cl
12 mmHg
Me

A067
O O

+ O o-C6H4Cl2 O
reflux
O O

A068
SeO2
Me Me Me t-BuOOH Me Me Me
H2O
Me OAc OAc
CH2Cl2 OH
0 oC
 Check Box
A069
O CH2
Ph3P CH2

Et2O
reflux

A070
O (EtO)3P O O
Br (EtO)2P
OEt reflux OEt

A071
O O

O (EtO)2P OEt
NaH OEt
benzene O
rt to 200 oC

A072
S
1)
H2N NH2
H2O, 70 to 100 oC
CN CN
Cl 2) aq NaOH, 45 oC HS

A073

O O 1) NaH, THF, 0 oC O O
PhSeCl, 0 oC
Me Me
2) aq H2O2
CH2Cl2, rt

A074
O 1) Me3SiCH2MgBr CH2
Et2O, reflux

2) NaH, THF
reflux
 Check Box
A075
CO2Me
Me Me Me Me
Pd(OAc)2 (cat)
Br Ph3P (cat) CO2Me

Et3N, 150 oC

Me Me Me Me

A076
Pd(OAc)2 (cat)
Ph3P (cat)
Na2CO3
OHC Br + (HO)3B OHC
n-PrOH-H2O
reflux

A077
O Pd(OAc)2 (cat) O
Me CuCl (cat), O2

DMF-H2O, rt
O

A078
PCy3
Cl
Ru
Cl
Boc PCy3 Ph Boc
N (cat) N
CH2Cl2
reflux
 福山研究室用每周一次小组会议 这些问题主要是让学生按顺序出题
◆专栏①◆
的时间，对反应机理的问题进行练 的。倘若不熟悉这样的套路的学生
习，练习时，手脑并用。所以学生 出不了几个问题来。所以出题的几
的书写的训练十分有效。国内外有 周前他们就开始骚动——与图书馆
些有机化学实验室，也有不少东西 山一般的论文搏斗。好不容易发现
是参考本研究室的练习，想通过本 一个挺好的问题，拿给前辈看，得
研究室将练习方法介绍过去。 到的却是“这个问题已经说
首先，问题是在前一周被事先分 了”“这还算个什么问题”等严厉
福山研究组

发，靠自己将这一周题解答。当然, 的语言。不过与此同时，他们自身
如果不明白反应剂之类的东西可以 的能力也在提高。为了找到更多的
通过参考书查询——但是这是在不 问题他们不得不读更多的论文，并
允许学生之间交流，自己出题的前 且适应这种简单而枯燥的工作。平
提下。这样可以让大家快速的解决 时仔细阅读论文,却怎么也出不了问
结构式与简式在题目中不同的问 题，只留下一双双悲伤的眼神。
会议景象

题。这样做是为了提升效率，不浪 问题的答案交流放在在小组讨论
费时间。如果谁出现一次出题失 后。负责的学生要清理研究室并把
误，就征收谁一次100日元的罚金， 文件保存成各种文件和PDF。由于主
聚集的钱就算是忘年会的时候的酒 页的各种原因，不予更新，但也有
钱了。 一定参考作用。
当时研讨会上出问题，会有四个 福山研究室地址
人走上黑板前,能够得意洋洋的书写 http://www.f.u-tokyc.ac.jp/-
答案。这不错,不过即使没有解开问 fukuyama/index-I.htm
题，在黑板前尴尬地站着，也是一
种修行——在那里,你的尴尬能够鼓
励你下次要奋发图强,如果又经历了
这样的问题，就有了经验。强烈留
在记忆中的答案会超越你的想象。
在出题方提示“已经15 ~ 20分钟
了，时间有限”后,出题人就会进行
以参考论文为基础的解说。
于是反应机理被详细讨论。如果
和论文记载反应机构不同的问题也
可以考虑。那个时候将有可能。包
括老师在内的全部讨论不一定是正
确回答,所以一定要考虑各种可能
性，才能更好的学习。
问题 中级编

中级编是研究生院入学考试与研究生院硕士课程的水平的问
题，还有大量有趣的人名反应的反应机理，如果分段来说中，
前半部分的问题比较基础，后半部分是以发展性的问题为作为
中心，可能后半部分问题做起来很没手感，因为有些包含了有
机合成化学的公式，希望你能把这些反应机理都写出来。
例 题 写出合理的反应机理

f uming H2SO4
MeCN-hexane
0 oC to rt

H2O, reflux OH
O
NH2

解 答

H O
O
HN
Me
H2O
-H+ +H+

OH
O
H2N
OH
Me

+H+
OH

N C Me OH
OH2
O Me
NH2

-H+ +H+
OH
N HO OH
C
O Me
Me H
NH2
-H+ +H+
-AcOH

O
HN
Me OH
NH2
H2O

Jacobsen, E.N. Org. Synth, Coll. vol Ⅹ 2004. 29

问 題 写出合理的反应机理 Check Box
B001
NaOH
Na2HPO4
CHO HO2C
(pH 2.5-4.5)
+ MeNH2 + O MeN O
CHO HO2C H2O,

B002
O OH
Al(i-OPr)3

i-PrOH
reflux;
aq HCl

B003
O NH2NH2 OH
AcOH (cat)
O EtOH, rt

B004
1) aqH2O2, K2CO3 O i-Pr
MeOH, 0 oC to rt Ar =
2) ArSO2NHNH2
O CH2Cl2-AcOT, rt i-Pr i-Pr
aq K2CO3

B005
O
CHO NaCN (cat)
CN
+ CN DMF
N 35 oC N

B006
Me Bn
Cl N
H
Me
HO S O
O
(cat)
+ Me Me
Et3N, EtOH O
O 80 oC

Me
 Check Box
B007
1) KOAc, Ac2O
reflux
H
O 2) aq HCl, reflux O CO2H
O

B008
O
O N O
Me
Me Me H aq HCl

KOH (cat) benzene

O MeOH, reflux reflux O

B009
O O
LiOMe
H + MeO2C CO2Me OMe
MeOH
reflux CO2H

B010
Me O H2C N N Me O

Ph OH Et2O, rt Ph OMe

B011
OTs
Li
liq NH3
O O

B012
CN NaNH2

liq NH3
Cl -78 oC CN
 Check Box
B013
NaNO2
NH2 aq HCl, 0 oC Cl

CuCl2 (trace CuCl)

0 oC to rt

B014

DCC, TFA O
Me pyridine Me
OH H
Me DMSO, rt Me

B015
HO aq HBr

H2O, 0 oC
Br

B016
OTs
H
t-BuOK
t-BuOH
OH 40 oC O

B017
n-Bu3SnH
Me Me H Me
AIBN (cat)
Me Me Me
I benzene
reflux H H

B018
O O

Ph O O Ph CCl3
(cat)

CHCl3, reflux
 Check Box
B019
O Cl

Cl O Me
o
Ph CH2Cl2, -7 C
N NH HCl
MeOH, reflux

B020
O OMe
Me3SiI H
C5H11 N CH2Cl2, reflux C5H11 N
CO2Me CO2Me
MeOH, rt

B021
EtO2C O Pd(dba)2, (cat) EtO2C
dppb, Et2NH
N O NH
THF, rt

B022
Ph

O O NO2 PhSH
S KOH
N N Ph
CH3CN H
50 oC MeO

MeO

B023
O O
BF3-Et2O CHO
O Me
Me benzene
Me
Me Me Me
B024
O Me
O Me S N O
O NO

aq KOH, EtOH
10 to 20 oC
 Check Box
B025

NC NC
Me
Me
Me o-dichlorobenzene HMe
180 oC

B026
O O
FeCl3

CH2Cl2
SiMe3 0 oC H

B034
1) O2, hv OH
acetone

2) Et3N, CH2Cl2
reflux
O

B035
1) O2, hv
acetone O

2) Ph3P
benzene

B041
PhCHO OH
CrCl2 (2 eq)
Me Br Ph
THF,
o
Me
0 C to rt

B042
H2, CO CHO
HRhCO(PPh3)2 (cat)
CHO +
n-Bu n-Bu n-Bu Me
benzene, rt
 Check Box
B045

O KSCN S
H Ph
Ph dioxane-H2O H
60 oC

B046
O O
Me2NH (1.1 eq)
Me Me
MeOH
MeO OMe Me2N

B047
1) Me2NCH(OMe)2
OBn pyrrolidine OBn
Me DMF, 110 oC

2) Raney Ni, NH2NH2

NO2 THF-MeOH N
H
rt to 50 oC

B048
O O
S NC

Me
O (TosMIC) CN
t-BuOH, EtOH
DME
5 to 40 oC

B049
1) CBr4 (1 eq)
Ph3P (2 eq)
O CH2Cl2, 0 oC
n-C7H15 H
n-C7H15 H
2) n-BuLi (2 eq)
THF, -78 oCto rt
H2O
 Check Box

B050
1) ArSO2NHNH2 Ph Ph
Me HCl, MeCN, rt Me i-Pr
O
Me Me OH Ar =
2) n-BuLi (2.2 eq)
THF, -78 oC to rt i-Pr i-Pr
Me Me Me Me
benzophenone
0 oC to rt

B051
O
MeO CO2Na
HO CO2Me

MeO AcOH NH
HO
+ MeOH-H2O OMe
HO CO2Me 35 oC
OMe
NH2
HO

B052

(HCHO)n
O O K2CO3 O O OH
H
MeOH OH
O reflux

B053
N

N
CO2Me O OH
(DABCO, cat)
+ Me Me CO2Me
H heat, rt

B054

N
H 1) aq HCl O
O TsOH CO2Me 60 oC CO2Me
xylene Et2O, rt 2) H2, Pd/Al2O3
reflux MeOH, rt
 Check Box
B055
O
Me S N3
O
O O Et3N O O

Ph OEt Ph OEt
MeCN
rt N2

B056
1) t-BuOK
Ts EtOH-toluene
N O
0 oC to rt H3N
2) aq HCl, rt Cl
S S

B057
Me Br2 Me
NaHCO3 NaOEt
CO2Et
Et2O, 0oC EtOH-Et2O
O reflux

B058
KOH
O O
I2 DMF, 60 oC

CO2Me MeCN-H2O MeI, rt

rt O O OMe

B059

H2C N N , 2 eq
O Et2O, rt O
MeO2C MeO2C Br
Cl HBr
B060

CO2H Ac2O
reflux
N N O
Me Me
 Check Box

B061
O
EtO P
EtO CN H
Me OH + H2N CO2t-Bu Me N CO2t-Bu
11 Et3N 11
Me OH O DMF, rt Me OH O

B062
O
PCl5 CN
NH2
POCl3
N 100 oC N Cl
O

B063
O O
DDQ
Me Me
OH OMe CH2Cl2 O

OMe

B064
O
1)
Cl S N C O
O (CSI) CN
OMe toluene, rt OMe

2) DMF, rt

OMe OMe

B065
NC
O
CO2H Br
N
t-BuNO, H2O H
NH2 Br
ClCH2CH2Cl
reflux
 Check Box

B066

OH
1) PhI(OAc)2
H
CF3CH2OH
O CO2Me
2) NaHCO3 N
MeOH O
OH H Cbz
NHCbz

B067

MeO2C
OH
DBU (cat) Me
Cl3CCN TfOH (cat) MeO2C
OH OBn
CH2Cl2 cyclohexane Me
CH2Cl2, rt

B068

t-BuOH, HCO2H
H2SO4

CCl4, rt CO2H

B069

n-BuLi Ph
Ph O Ph Ph
Et2O, rt
OH

B070

OH
Ph N
NaH Ph
Ph CO2Me CO2Me
DMF-dioxane O
rt
 Check Box

B071
S
N
N n-Bu3SnH
O H Me
AIBN (cat)
O
benzene, reflux
OH
Me

B072

O O
S Br
Br Br
Me hv Me t-BuOK

CH2Cl2, -15 oC t-BuOH-THF

SO2CH2Br 0 oC to rt
H

B073
KNH2
Me Me Br hv Me
+
O THF, rt O

B074

S Bu
O hv N
N Bu BF3-Et2O N
O N S
THF, rt

B075
1) CHBr3, t-BuOK
petroleum ether
Me 0 oC to rt Me

2) MeLi
Me Me
Et2O, 0 oC to rt
 Check Box
B076
O

Cl3C OEt Cl

NaOMe
Cl
petroleum ether
0 oC to rt

B077
1) Cl3CCO2H, Cl3CCO2Na
DMF, rt; Ac2O, rt
Zn, AcOH, 60 oC
CHO
2) MeLi, THF, -10 oC
H3O+

B078
BnNH2
aq HCHO
OH
TFA
SiMe3
H2O, 25 oC NBn
H

B079
O
Me Me O Me Me
S
Me HN NH2 Me
H Me H Me
NO2
Me H Me H
EtO2C N N CO2Et
H H H H
Ph3P, NMM
HO -30 oC to rt H

B080
1) Ph3P CHCO2Et
CHO benzene, reflux

NO2 2) (EtO)3P N CO2Et

170 oC H
 Check Box
B081

H2N CO2H NaNO2 Cl CO2H

H aq HCl H
Me Me
rt

B082

MeO NaNO2
A
aq HCl, 0 oC
NH2

1) KOH, EtOH-H2O
A
O 0 oC MeO Me
CO2Et
Me 2) aq HCl, EtOH
Et N CO2Et
65 oC H

B083

O (C6H13)3B O
N2 C6H13
Ph THF-H2O Ph
reflux

B084
O I2, AgNO3
HC(OMe)3 OMe
Me
MeOH O
i-Bu reflux; i-Bu
H2O

B085
Me Me Me Me
H2SO4

Ac2O
Me -20 oC to rt
O O
SO3H
 Check Box
B086

OMs
Me B2H6, THF

aq NaOH Me
reflux

B087
1) Br2, CHCl3-CH2Cl2 Me
Me
0 oC
O O
2) t-BuOK, Et2O
Me 65 oC Me

B088

N
N H
+
N N toluene
O MS 4A N
reflux

B089
OH
N aq NaOCl N O
Et3N
H +
CH2Cl2
0 oC

B090
PhN C O (2eq)
N Me
Et3N O
O2N Me + AcO
benzene
AcO
rt to 80 oC

B091
CH3C(OMe)3
Me Me
EtCO2H (cat)
EtO2C
HO 138 oC
Me Me
 Check Box
B092
O
PhCHO Me
Me CSA
N Ph
H Me OMe benzene N
reflux

Me

B093
1) TBSOTf , Et3N
O CH2Cl2
-78 to 0 oC HO2C OMe
O
2) toluene, 110 oC;
1 N HCl, THF, rt
OMe

B094
O
S
Ph
Me NaH
CHO
THF decalin Me
rt 150 oC
OH

B095
1) 1,3-dithiane, 20 oC
2) n-BuLi, THF
-78 oC
Br
3) HgCl2, MeCN-H2O
reflux CHO

B096

Br H CO2Et
Me
N CO2Et N
CHO K2CO3 Me H
DMF toluene
OH H
20 oC reflux
Dean-Stark trap O
 Check Box

B097

1) NaOCl, pyridine NOH

Me
AcO -78 oC AcO

Me 2) hv , benzene, rt Me
AcO AcO
H 3) THF-i-PrOH H
Me OH Me OH
OAc reflux OAc

B098
O NO2
hv O
Ph O
Ph OH
CCl4, rt

B099
O
Me P(OEt)2
O O n-BuLi Me O
THF
-78 oC

B100

PPh3 Br
NaH
CHO
N Et2O N
H reflux

B101
N3 H
Ph3P N
Ph H H
Ph
OH toluene Ph Ph
reflux
 Check Box

B102
Ph3P Se
H O H TFA
Ph Ph Ph Ph
CH2Cl2, rt

B103
S
1)
N N N N
HO OH toluene, reflux

Ph Ph 2) (MeO)3P Ph Ph
reflux

B104

O Me3SiI (2 eq)
C8H17 C8H17 CCl4, rt C8H17 C8H17

B105

OMOM 1) Pt[(H2C=CHSiMe2)2O]2 OMOM

C6H13 toluene, 60 oC C6H13
O H 2) 30% H2O2, aq KOH
Si OH OH
Me Me MeOH-THF, rt

B106

Me Me PhSCl Me Me
Me Et3N
OH
CH2Cl2
Me -78 oC to rt Me
Me
SPh
O
 Check Box
B107
O Me
HO
SmI2 (4 eq)
MeO I
Me THF-HMPA O
O 0 oC to rt Me

B108
MeO OMe MeO OMe
Me Hg(OTf )2 (1% mol) Me

MeNO2
0 oC H
Me
Me

B109
PCy3
Cl
Ru
Cl
PCy3 Ph MeO2C
O (cat) O
MeO2C H N
CH2Cl2 H
reflux

B110

SMe2 I
NaH NaN3
CHO N3
N o
THF, 0 C H2O, 0 C o N
H
OH
B111
O Ph
TfOH
N (n = 1)
Me
CH2Cl2
O N3 0 oC
O
Me n Ph TfOH
Me (n = 3)
CH2Cl2
0 oC NHPh
 Check Box

B112
O O O O
S S
N Tol S S Tol O
Et3N aq HCl S

MeCN, reflux 50 oC S

B113
Ph
t-BuOK
O PhCHO O
AcN HN
NAc t-BuOH-DMF NAc
O rt O

B114
O

Me
Me
N
OH CSA (0.1 eq)
Me

CO2H THF, 0 oC toluene O

reflux
O

B115
Na (4eq)
CO2Et Me3SiCl (4 eq) OSiMe3

toluene
CO2Et reflux OSiMe3

B116
O3
MeOH-CH2Cl2
-78 oC;
TsOH
-78 oC to rt OMe

NaHCO3 MeO CHO

(neutralize);
Me2S
 Check Box
B117
O3
M OH-CH2Cl2
e
-78 oC; OMe

evaporation; O CHO
Ac2O, Et3N
0 oC

B118
OEt n-Bu3SnCl (cat)
I NaBH3CN OEt
O AIBN, t-BuNC O

t-BuOH, reflux

CN

B119
O
N3 BF3-Et2O N O

CH2Cl2, rt

B120

Ph O
NMO, Et3N
NOH N Ph
Cl CH2Cl2 O
rt

B121
O O

decalin
290 oC
 Check Box

B122
Me Me 1) CH2N2, Et3N Me Me
Et2O, 0 oC

2) 95 oC
O O
SO2Cl

B123

PPh3Br
O
t-BuOK

THF, rt

B124
1) CHCl3, reflux
OTBS
2) PhSeCl, CH2Cl2 Me
O -78 oC
O
Me 3) aq H2O2, THF
0 oC H

B125
1) ClCH2COPh, K2CO3
THF, rt
S
Ph SH
2) hv , cyclopentadiene
Ph
CH2Cl2, rt

B126

Me O Me
Me rhodium(II) mandelate
AcO
N2 CH2Cl2
AcO reflux Me O
 Check Box

B127
Cr(CO)5 OMe
Ph Ph Ph
OMe
n-Bu2O Cr(CO)3
Ph
45 oC
OH

B128
Ti(Oi-Pr)4 (cat)
O EtMgBr (2 eq) Me OH
Me OMe Et2O, rt
 关于解开反应机理的问题，在附录 3.考虑多种可能性
◆专栏②◆
里也叙述了一样的基本的化学知识， 实际的反应机理不只是单纯的一
当然本章也有一些额外的技巧。 条，而是有无数的分歧点与无数的
1.写好有机化学的结构式 可能性。在多种可能性中考虑出即
写好有机化学中的结构式是一件很 将书写的反应机理优先顺序与选择
容易的事。需要做的就是在解决问题 性是非常重要的。如果发现自己考
的时候，把当前所想到的结构式，统 虑的那种可能性不太恰当，就在分
统写下来。无论是在脑子里出现的结 歧点中仔细观察分子的完整结构，
构式、还是在眼前浮现的结构式，在 找出下一步的反应方向。观察反应
机理书写问题的解决方法

纸上把它们写下来对下一步的推理肯 物与生成物的结构对于机理的书写
定有用处。另外请一定要仔细地、用 很是有用。尤其是从生成物逆推，
心地写好反应后的结构式，因为在分 能轻松地找出几个重要的中间体
子在反应中不断长大的同时，有时有 来。
一些不起眼的官能团会被我们一不小 4.试着开始数反应点
心就省略了。最后，在实际的合成 解决问题的过程中，如果突然在
中，反应条件是根据整个分子的结构 这种时候卡住了，可以数一下反应
来设计的，请一定要好好看完整分子 点。如果只有五六个原子的分子在
的结构，不要漏掉什么反应的重要条 反应，大多数发生的就是分子内反
件。 应。本研究室中如果有那样问题都
中间体的书写方面也需要你用心去 想不出来学生的话，我们称之
想，在头脑中想出合理的反应机理。 为“幼儿园没毕业的傻瓜”。毕竟
实际上如果你只写出起始的原料和产 幼儿园里还不会数数的小孩子都是
品，你就会养成这样的坏习惯.这会 屈指可数。
导致你在反应的重要的转折点中的中
间体会错过很多个结构式，因此，在
每个中间体中最好请画上三个箭头。
2.预先知道反应剂是什么
在完全不知道的反应剂的使用的方
法的情况下，想要解决那种问题是很
难的，关于反应剂，我们需要某种程
度上的必要的的知识，所以，请多看
资料书，以了解它们的用处。在反应
机理的书写中的反应剂非常重要，如
果不知道反应剂的作用可以类比其他
已知的反应剂来书写机理。调查出反
应剂的作用不只是为了解决这一个问
题，是为了解决以后更多机理的书写
问题打下基础。
问题 上级编

上级编中的问题来自历史上最新有名的反应的论文，收录了各
种反应的问题，不过如果按照基本方法去做，依然能够能找到
答案。问题的顺序是完全随机配置的，大概是按着难易度顺序
编排的。一个一个踏实地去做，不会做的话不要气馁，多挑战
几次吧。
例 题 写出合理的反应机理

Hg(OAc)2
AcOH, 70-75 oC CO2Me
+ AcO
OAc
MeO2C CO2Me CO2Me
benzene, reflux

解 答

H OAc

H OAc

H
AcO
OAc
Hg
H OAc AcO CO2Me

MeO2C
H

HgOAc
OAc AcO
H

AcO
CO2Me
H Hg OAc
CO2Me
O

H O
Me

CO2Me AcO
H OAc +
O CO2Me
Me AcO
O
H

AcO
OAc

Noller, C. R;Dinsmore, R. Org. Synth. Coll. vol Ⅱ 1943. 358

问 題 写出合理的反应机理
Check Box

C001
O MeO OMe
OMs NaOMe OH
Me H MeOH, rt Me H
t-Bu t-Bu

C002

O2N SO2 NH2

O
NO2 CN
Cl
Et3N, THF
MeO reflux MeO

C003

H Me
Me
Me TiCl4 H Et
Me Et CH2Cl2 Me Me O
O -78 oC

C004
MgBr
O O
THF, 0 oC

Cl heat, 200 oC

C005

1) TfOH, CH2Cl2, 0 oC
Me OH CO2Et
pyridine Me OH
SiPh3
EtO2C
2) toluene, reflux OH
3) TBAF, H2O2
DMF, 55 oC
 Check Box
C006
NHTs
1) TsNHNH2 OH
Et2O
O
2) NaH N
DMF, 120 oC H Ts
O

C007
Me
Me O CHO
O
O
Ph CO2H H
t-Bu N C N
toluene Ph N t-Bu
Ph NH2
-30 oC to rt O
Ph Me
Me

C008
OBn
OMe
OMe BnO OMe

OMe
HO
toluene
O
110 oC OH
OMe Me
O O O

Me

C009
O
F3C HO2C CF3 Ph
N KOH NH
OH +
O F O Ph dioxane, rt
O Me
H2O

C010
PhI Ph
Pd(OAc)2 (cat)
NaOAc, LiCl

DMF, 100 oC
 Check Box
C011
MeO2C

CO2Me PhCl
190 oC

C012

O
N Et
N N
H Ac2O
Et
85 oC
O N
H
HO OAc

C013

OH 1) t-BuOOH, VO(acac)2 OHC

H O
O CH2Cl2, -30 oC
OMEM MEMO
Me Me OH
2) toluene, 110 oC
H MeMe

C014

1) NOCl
o
pyridine, 0 C
OH OH
2) hv , pyridine NH
Me 3) TsCl, pyridine Me
benzene, rt O

C015
O 1) Rh(OAc)2 (cat) HO H O
O O
N2 CH2Cl2
Me +
2) SmI2 O
THF, 50 oC H
 Check Box
C016
1) Me3Si N2
O BuLi,
Me
Me DME-hexane
Me
O O
2) silica gel HO O Me

C017
1) H2C CHMgBr
THF, -10 oC
O 2) DBU, Cl3CCN OH
CH2Cl2, rt
N H N NH2
3) Ca(OCl)2 Cl
N CH2Cl2-H2O, 10 oC N
Tr Tr
4) aq HCl
THF-H2O, rt

C018
MeO OMe

MeO OH MeO
1) EtMgBr, THF-H2O
Me OH
2) benzene, reflux
Me
OMe OH Me OMe Me
Me
Me

C019
1) TsNH2, BF3-Et2O Ts
O benzene, reflux N Ph
Ph H 2)
CO2Et CO2Me
ca
Ph3P ( t)
benzene, reflux

C020
Ti(OPr)4 1) FeCl3 O
CO2Et
i-PrMgCl (2 eq) pyridine, DMF

TBSO Et2O 2) NaOAc, MeOH TBSO

 Check Box
C021
Me
Me
N Li
Me
Ph Me n-BuLi Ph
Cl + OH
Cl O Et2O Et2O-hexane

C022

1) pyrrolidine
toluene, reflux
2) (PhO)2P(O)N3
toluene
O rt then reflux
CO2H
3) KOH
ethylene glycol
reflux

C023

TMS

1) LiI, EtOAc O
reflux
O O CO2Me
2) Ac2O
Me N Me N
70 to 125 oC

C024

1) PhSeBr, i-Pr2NEt
Me MeCN, 0 oC Me

O OH 2) NaIO4, NaHCO3 O
MeOH-H2O, rt
3) hexylamine, MgSO4 O
toluene, reflux
 Check Box
C025
O
AcO HgCl2 AcO
O
H2O-caetone
BnO OMe reflux BnO OH
OBn OBn

C026
1) LiO-i-Pr (cat)
O O Et2O, rt OH OH
Me + Me Me
Ph H 2) NaOH, MeOH Ph
Me reflux Me Me

C027

H O BF3-Et2O
O
ethylene glycol Me OH
O O
CH2Cl2, 20 oC
Me Me
Me

C028
1) MeAlCl2
O CHCl3, rt
Me
MeN 2) NaBH4
Me
O O MeOH, 0 oC
NMe
MeO Cl 2,6-lutidine 3) MsCl, Et3N MeO
Me toluene, rt CH2Cl2, -78 oC Me
O
4) t-BuOK
THF, reflux

C029
1) CH3CHO
BH2 Et2O, 0 oC
H
Me 2) Cl2CHOCH3
t-BuOLi, Et2O H
B 0 oC to rt
H
Me
Et2O 3) H2O2, NaOAc
-20 oC H2O, reflux H
O
 Check Box

C030

PhNC
O Me3SnSnMe3 O
N N
hv
I N
benzene
Et 20 oC Et
OH O HO O

C031
Me
O OH OH Me
Me
+ Me
PhNEt2
230 oC
Me Me Me

C032
Me Me
Me Me
N C N S Ph
HO O benzene, reflux;
O

Ph S Ph Ph

C033
n-BuLi, THF n-BuLi (1 eq) HO Ph
-78 oC; THF, -78 oC; OHMe S
Me H
O
O
OH PhSCl OHMeCHO
Me Me
-50 to 0 oC Me O O
O H Me
Me
Me O O
H Me
(0.4 eq)
aq NH4Cl, rt
 Check Box

C034
OTBS PCy3
Cl
Ru OTBS
Cl
PCy3 Ph
(cat)
benzene
Me rt, 4h

C035

OBoc OBoc
OEt PhMgBr
+
Et2O
OBoc -78 oC to rt O

O H Ph OEt

C036

OBn NBS OBn

O MeOH O
BnO BnO
BnO O BnO OMe
OBn CH3CN OBn

C037

Me
Li Cl
Me O Me
Me HgCl2 (cat)
Me
Me S Et2O H2O Me
Me Me
-78 to 20 oC

C038
O 1) N3CH2CO2Me
NaOH, MeOH, rt
H
2) cyclohezane, reflux
N CO2Me
3) p-xylene, reflux H
 Check Box
C039
OLi
1) Li
Me
Et2O O
O -78 oC to rt

2) H2SO4
Me
MeOH Me Me
0 oC

C040
OH HO Me Me
Me
OMe PhI(OCOCF3)2
H
THF mesytilene O
Me rt 200 oC O OMe

C041
MeO MeO
hv
N O NaBH4 N O
MeO MeO
H H
MeOH
5 to 10 oC H

C042
TMS O
O TBSO O
LDA TBS
Me
THF, -80 oC THF
(CH2)4CH3 -80 to 30 oC TMS (CH2)4CH3
C043
SmI2
Me HMPA HO
t-BuOH Me
H H
O O
THF
0 oC H
O
 Check Box
C044
O
Me O Me
NaOMe
H
OTs MeOH
H H reflux
MeO
Me Me
O O

O O Me O
(M eldum's acid)
H O
H2NCH2CH2NH2 2AcOH (cat)
H H
Na2SO4, MeCN, 20 oC
reflux MeO

C045
t-BuLi (4 eq), THF Me
O
-78 to 0 oC Me
Me
OEt
Br Br O
OH
Me
CO2Et
-78 oC

C046
MeO2C
Me OMe CO2Me
O H
Me O
N N toluene OMe
reflux O

C047
1) NaH, Me CH2 Br
DMF, 60 oC
2) LiAlH4, AlCl3
MeO MeO
O Et2O, 0 oC CN

N Ph 3) mCPBA, CH2Cl2, rt N Me
H
KCN (excess)
Ph
DMF-H2O, 50 oC
 Check Box
C048
1) O S N CO2Me
benzene, 0 oC
2) PhMgBr H
THF, -60 oC NH
3) (Me2N)3P O O
H
-78 oC

C049

Me Me Me
1) LDA, TBSCl
HMPA, THF OH OH
+
O 2) O3, CH2Cl2, rt Me Me
3) H2, Pd/C, EtOH, rt Me OH Me OH
Me Me

C050

OMe benzene, 0 oC OMe Br

Br Br Ph3P CHCN PhMgBr Br Br OMe
EDCI THF, -60 oC
O
CH2Cl2, rt H2N Br
CO2H N
H
OMe O

C051
O
1) O O

AcCl H
NH2 toluene, reflux O
N
CO2Et
Pr 2) NaBH4, H2SO4
Pr
EtOH, -30 oC
3) Me3SiCH2MgCl (2 eq)
CeCl3, THF;
aq HCl
 Check Box
C052

1) (COCl)2, benzene
CO2H 2) Et3N, toluene, reflux

3) MeLi, THF, -78 oC

4) Mn(OAc3), Cu(OAc)2 Me
O
EtOH, rt

C053

TMSOTf (0.5 eq) Ph

OH
MS 4A O
CHO +
Ph Ph
SiMe3 CH2Cl2
-78 oC
Ph

C054
LiCHBr2, THF
n-BuLi (2 eq) OH OSii-Pr3
O N2
O -78 to 25 oC O
O i-Pr3SiCl hv O OSii-Pr3
ClCH2CH2Cl
rt to reflux

C055
H
N
Ts Ts Me
Ph
n-BuLi (1 eq) N

OTf
Me I
Ph Ph
THF, reflux

C056
OBn OBn
H
O
1) NH3, CH2Cl2, 0 oC H
OHC
2) NH4OAc, AcOH, 75 oC HN
 Check Box

C057
H2
Lindlar catalyst H
quinoline H OH

HO OH CH2Cl2-MeOH
25 oC HO

C058

O Tol Zn(Cu) Cl
S Cl
O O Cl3CCOCl O O O
Me Me
THF, -45 oC O
N(Boc)2
STol
N(Boc)2

C059

O Me
Me
Cl S O
MeO S MeO
Me Me AlCl3 Me Me
CN CN
N CH2Cl2 N
0 oC

Cl Cl

C060

1) Pd2(dba)3-CHCl3 (2.5 mol%) O

Me
DPPE, MECOCH2CO2Me
Me O THF, rt OMe
O
2) silica gel Me
Me
 Check Box
C061
Me
Pd(OAc)2 Me
Ph3P, Ag2CO3

MeCN
Br 130 oC O
O

C062
Me3Si OH
O OH
TsOH EtAlCl2 O

benzene decalin CH2Cl2

H OH
175 oC -78 oC

C063

H 1) NBS, BaCO3
O OMe CHCl3, reflux OH
O
OH O
BzO
Ph O 2) activated Zn Me
H Me i-PrOH-H2O
reflux

C064

n-BuLi

330 oC
N NHTs

C065
NO2

SO2NHNH2
SiMe3 SiMe3
TBSO DEAD, Ph3P
TBSO C H
OH THF H
-15 oC to rt
 Check Box
C066
BrMg
(excess)

NO2 THF N
-40 oC H
Me Me

C067

O TiCl4-(THF)2 (cat) Me O
N i-Pr2NEt
+ Cl N
O
Me Me CH2Cl2, rt Me O
sy n : anti = >99 : 1

C068
1) Zn(Cu), Cl3CCOCl
Et2O, reflux
2) Zn, HOAc, 85 oC
S O
3) HF, MeCN-H2O, 20 oC
TBSO HS O
4) CSA, hexane-CH2Cl2,

C069
1) ZnCl2, hv H I
OMe H
CO, THF
(OC)4Cr + H
Me N 2) I2, MeCN, rt N Me
Bn OMe
O

C070
Me Me
1) ClOC OAc
OH OH (2 eq)
O O
MeCN

OH OH OH 2) NaOMe, THF OH
 Check Box

C071

O CHO NBn
NHBn MS4A

CO2Me BF3-Et2O O
N N
H toluene, reflux H
CO2Me

C072
1) H2C CHCN
MeOH
2) H2C CHCH2Br H
NaH, THF N
N
H OH 3) mCPBA, CH2Cl2, Me
4) MeOH, heat
5) H2, Pd/C, MeOH

C073

O O
MeLi (cat) O
O Ph2O, 180 oC
OH
TBAF H

TMS
H O

C074
O 1) NaOH, THF, rt O
N2 + S N 2) Rh2(OAc)4 N
H
benzene, reflux
3) Raney Ni, acetone

C075
1) Rh2(OAc)4 Me H Me
O O OH HO
+ benzene, reflux
Me OMe Me Me MeO O
2) BF3-Et2O
N2 benzene, rt O Me
 Check Box
C076
1) LiSnMe3, THF
O
Me
O , BF3-Et2O Me O
o
-78 C
O
2) Pb(OAc)4, CaCO3
benzene, reflux
3) H2, (Ph3P)3RhCl

C077
H
n-BuLi
O
O
THF, -85 oC

Me Me

C078
CHO Me Me OAc Me Me
1) C6H11NHOH, NaHCO3 OHC
Me EtOH, rt Me

O 2) AcCl, Et3N, Et2O, 0 oC to rt O

O 3) NaOAc, AcOH, rt O
Me Me
Me Me

C079
1) O2, hv
rose bengal TBSO
OTBS
Me MeOH-CH2Cl2 H
Me2S
HO O
O 2) Ac2O, Et3N
OTBS
DMAp, CH2Cl2
OTBS O
3) DBU, toluene
110 oC

C080
O O
Et3N hv
Cl
benzene CH2Cl2
reflux
O
 Check Box

C081
O O
Me Me
Me SiMe3 TiCl4
+ C SiMe3
CH2Cl2
Me
-75 to 0 oC H
Me Me

C082
Me

O O O
n-BuLi
Et OH THF, 0 oC Me Ph O Et
Ph Me Ph2PCl, 0 oC PhCO2H Ph Me
CH2Cl2, rt

C083
Me 1) KHDMS
OMe OMe
Et2O
MeO Cl MeO

H 2) O3, CH2Cl2
-78 oC; O
BnO Ph3P
TsOH Bn
benzene

C084
O
Bn N C NHBn
N CO2H
N Bn N Bn
MeOH toluene
Ns rt reflux NsHN
O
C085
Mg
Et2O, rt; Me
Me Me
Li SOCl2 60 oC
O
OH
H Me THF Et2O H2C CHCHO Me
-70 oC to rt rt -10 oC to rt MeH
 Check Box

C086
O
t-BuOK, THF, rt;
P Ph
P ClO4 Ph
CO2Et
Ph Ph Ph EtO Ph
reflux

C087
CO, Pd(PPh3)4
K2CO3, n-Bu4NBr
O
I O

NHTs MeCN, 70-80 oC N

Ts

C088
O Li LiBH(s-Bu)3 Me
SPh HBF4 MeLi, KOEt
Me
THF 0 oC Et2O, rt THF, rt

OH

C089

Boc 1) LDA, Et2O

N 0 oC
O NBoc
2) KH, CS2; MeI
THF, 0 oC
3) n-Bu3SnH, AIBN
toluene, 100 oC

C090
Me O

MeN NMe
N (HCHO)n
H Na2SO4 N
Me
HO N O N
MeCN
N NMe reflux
O
Me
 Check Box

C091
Ph
NO2 HO OH
O NaHCO3 NiCl2/NaBH4
Me
Ph SnCl4, CH2Cl2, -78 oC benzene EtOH, rt H2N
reflux Me Ph

C092

ClSN O
Me BF3-Et2O Me
Et3N H2O
BnO BnO
OH Et2O dioxane
-78 oC 0 oC

C093
1) Me
(OC)5Mo
HO Tf 2O O Me4N
pyridine CH2Cl2, 0 oC H
CH2Cl2 2) benzene, 65 oC O
0 oC Me
EtO2C CO2Et

C094
1) t-BuOK, t-BuOH
-5 oC to rt
Me 2) O3, NaHCO3 O
Me
O Me MeOH-CH2Cl2, -70 oC
CO2Me
Me 3) Ac2O, Et3N, DMAP
Me benzene reflux
Br Me Me

C095
Me
H Me H
TMSOTf
H
O toluene
rt OSiMe3
Me Me
 Check Box
C096
MeO 1) PhLi, Et2O; O
H H3O+ OH
O 2) TsOH, H2O
Me CH2Cl2 Me

C097
1) Br2, CHCl3, rt
O
Me3Si 2) AgNO3, MeOH
reflux
CO2Me CO2Me
3) TFAA, DMSO
CO2Me CH2Cl2 CO2Me
-78 oC to rt

C098
1) NH2OH-HCl
O NaOAc
MeOH, rt
NC
N
2) sealed tube CN
CN CN O
toluene, 160 oC

C099
TBS TBS
1) SPh2 BF4
O O O
KOH, DMSO
O PhS
OH aq BF4, Et2O, rt O H
PhS
H H 2) PhSSPh (excess) H H
NaOMe, MeOH,

C100
1) S CO2Me
Cl
pyridine, CH2Cl2
OTs 2) mCPBA (2 eq)
Me Me CO2Me
CH2Cl2

N CO2t-Bu 3) KOMe, THF-MeOH N CO2t-Bu

Boc 4) SmI2, THF-MeOH Boc
 Check Box

C101
OMe

hv
S OMe
toluene S

C102
BF3-Et2O
EtO OEt OSiMe3 CH2Cl2, -75 oC O O
+
CH3CO2H
OSiMe3
-75 oC to rt

C103
1) NH2OH-HCl
O NaOAc, MeOH, rt
H
2) NaBH3CN, MeOH, rt Me H
N
3) (HCHO)n, MS4A Me
Me HO
H toluene, reflux
4) MeOSO2F, ether, 0 oC
LiAlH4, THF, rt

C104

AcO CO2Et
CO2Et Ac2O (10 eq)
MeO NaOAc (2eq) MeO
CO2H reflux OAc
MeO MeO

C105
Me Me H
Me 1) hv
O acetone
O H
Me O
O 2) H2, Pd/C H
MeOH, rt Me Me O O
 Check Box
C106
H Ph
Ph
H
Ph O
N toluene
N H
O O 110 oC

OH

C107
Cl quinoline
Cl 210 oC
S Cl

C108
1) KH (excess)
18-crown-6, THf , rt
OH ClCO2Me (excess) H
o
pyridine, -78 C to rt
NH N OMe
2) KOH, MeOH-H2O, rt O
CN O

C109
1) mCPBA, CH2Cl2, 0 oC Me O
Me
2) aq HBF4, CH2Cl2, rt
TBSO TBSO

3) BrMg Me ,CeCl3
THF, -78 oC to rt
4) PdCl2(MeCN)2 (1 eq)
DME, rt
解答 初级编
A001
OH
O O OH O
O2N O2N O2N H
OMe OMe O
A B C
OH

O O O
O2N aq HCl O2N O2N
O O H OH
D

Kamm, O.; Segur, J. B. Org. Synth. Coll. Vol. Ⅰ 1941, 391

A: Addition of hydroxide ion to the carbony group to form a tetrahedral intermediate. B : Elimination of
methoxide ion helped by the oxygen lone pair. C: Deprotonation. pKa AcOH = 4.8, H2 O = 15.7. D:
+
Protonation on work-up. pKa H3O = -1.7.

A002
H H
O H O HO O Et HO OEt
-H+
OH OH OH OH
A B C
EtOH

H
HO OEt O O
+H+ -H2O -H+
OH2 OEt OEt
D E F

Fischer, E.; Speier, A. Ber. Deut. Chem. Ges. 1895, 28, 3252
A: Acti vation of the carbonyl group by protonation. B: Additiono f EtOH to the activated carbony group.
C: Deprotonation of the oxonium ion. D: Protonation makes a hydroxy group a good leaving group.
E: Elimination of water helped by the oxygen lone pair. F: Deprotonation

A003
O
O
S
O S Cl O Cl
Cl Cl
Me OH A Me OH B
 O Cl
S H
Cl O -SO2 O -H+ O

Me OH Me Cl Me Cl

or
O
O
S
O S O Cl
Cl Cl
H
Me OH A Me O

O O O
O
S C
Me O Cl C Me D Me Cl
Cl
Helferich, B.; Schaefer, W. Org. Synth., Coll Vol Ⅰ 1941, 147.
A : Atack of a carboxylic acid to SOCl 2 forms a mixed anhydride. B: Addition of chloride ion to the
carbonyl group to form a tetrahedral intermediate. C: Formation of an acylium ion. D: Addition of
chloride ion to the acylium ion

A004
O BrMg O Ph O
-EtOMgBr
Me OEt Me OEt Me Ph
A B C
Ph MgBr Ph MgBr

H
Ph Ph aq NH4Cl Ph Ph Ph Ph
Me O MgBr Me O Me OH
Allen, C. F. H.; Converse, S. Org. Synth., Coll. Vol. Ⅰ 1941, 226.
A: Addition of PhMgBr to the carbonyl group of the ester to form a tetrahedral intermediate. B: Elimi-
nation of ethoxide ion to form a ketone. C: Addition of PhMgBr to the more reactive ketone to form a
tertiary alkoxide.

A005
 Mg H
N N aq H2SO4 N
MeO C
MeO MeO
A Ph Ph
Ph MgBr

H H H H
N H N H2N O H H2N OH
-H+
MeO MeO MeO MeO
Ph Ph B Ph Ph

H2O

H
+H+ H3N OH O -H+ O
MeO MeO MeO
C Ph D Ph E Ph

Moffett, R. B.; Shriner, R. L Org. Synth., Coll Vol. Ⅲ 1955, 562.

A: Addition of PhMgBr to the nitrile forms an imine anion, B: Addition of water to the iminium ion gives
a hemiaminal. C: Protonation occurs on a more basic amino group. pKa H3O+ = -1.7, EtNH3+ = 10.6.
D: Elimination of ammonia helped by the oxygen lone pair. E: Deprotonation.

A006
O
H
Me
H N H O MgBr H O
Me Me aq HCl Me
N N
A Me Me B
MgBr

H H
OH OH O O
Me H -H+
N N H H
C Me D E
Me Me

Olah, G. A; Surya Prakash, G. K.; Arvanaghi, M. Synthesis 1984, 228

A: Addition of PhMgBr to the carbonyl group. The resulting tetrahedral intermediate is relatively stable
because the alkoxide anion cannot generate an amine anion ( pKa i-PrOH = 17, Et2NH = 36). B:
Protonation on workup. C: Protonation of a more basic amino group. pKa H3O+ = -1.7, EtNH3+ =
10.6. D: Elimination of the amine helped by the oxygen lone pair E: Deprotonation.
A007
O
H
O R'
O R
N C N N C N R'
O A H B

EtO2C
Me
N
Me
O Me R
N
R N N
Me O
O O
N R' C N R' D
R' NH R' NH

O
O Me
R' R' Me
R' R' N - N N Me
N N Me H N
H Me O Me
R N Me R N
Me H
Me O O O
Me

Me O
N
Me -DMAP OEt
Me O N Me O
E Me F
Me R O Me
Me O
Neises, B.; Steglich, W. Org. Synth., Coll. Vol. Ⅶ 1990, 93.
A: Acti vation of DCC b y protonation. B: Addition of the carbo xylate to the protonated DCC. C:
Addition of DMAP to the carbonyl group. D: Elimination of a urea anion which then abstracts a proton
from an alcohol. E: Addition of the alkoxide anion to the carbonyl group to form a tetrahedral
intermediate. F: Elimination of DMAP to form the product.

A008

HO H HO
H H OH H
O O HO
HO O -H+ HO O

A B C
 HO

O
+H+ H2O O -H2O O O H -H+ O O
OH
D E

Daignault, R. A.; Eliel, E. L Org. Synth., Coll Vol. Ⅴ 1973, 303.

A: Activation of the carbonyl group by protonation. B: Addition of ethylene glycol to the activated
carbonyl group. C: Proton transfer. D: Elimination of water helped by the o xygen lone pair. E:
Intramolecular addition of the second hydroxy group.

A009
H H H
O O HO O Me
-H+
H H H
A B C
BnO BnO BnO
MeOH
OH OH OH

H Me
HO OMe H2O OMe O
+H+ -H2O
H H H
D E
BnO BnO BnO
MeOH
OH OH OH

H
MeO O Me OMe
-H+
H OMe

BnO BnO
OH OH

H
H
MeO OMe MeO O Me -MeOH OMe OMe
H
H OMe F H OMe H OMe G O OMe
H
H2O
 H
H Me
-H+ OMe +H+ O -MeOH
H -H+ H
H
H HO OMe HO OMe I O OMe O OMe

Baker, R.; Cooke, N. G.; Humphrey, G. R.; Wright, S. H. B.; Hirshfield, J.

J. Chem. Soc., Chem. Commun. 1987, 1102.
A: Acti vation of the carbonyl group by protonation. B: Addition of MeOH to the activated carbonyl
group. C: Proton transfer. D: Elimination of water helped by the oxygen lone pair. E: Addition of
MeOH and protonation to form a dimethyl acetal. F: Trimethyl orthoformate serves as a scavenger of
water to let the equilibrium to the product side. Protonation followed by elimination of MeOH. G:
Addition of water. H: Proton transfer. I: Elimination of MeOH followed by deprotonation to form
HCO2Me.

A010

H OH OH
O O
O O O O H -HBr
H
Br Br Br
A B C

OH Br
O
O O H -HBr O O
Br Br Br
D E

Aben, R. W. M.; Hanneman, E. J. M.; Scheeren, J. M. Syn. Commun. 1980, 10, 821.
A: Protonation. B: Cleavage of the dioxolane ring helped by the oxygen lone pair. C: Deprotonation
to form an enol ether. D: Bromination of the electron-rich enol ether. E: Intramolecular addition of the
hydroxy group. Opening of the dioxolane ring of the product is more difficult because of the
electron-withdrawing bromine atom.

A011
H H H H
O O HO NH2 -H+ HO NH2 +H+
Me H A Me H B Me H Me H C

NH3
 N N H
H2O NH2 -H O NH2 H2N C aq HCl H3N C
2
Me H Me H D Me H E Me H F
CN

H H
NH -H+ NH -H+ NH2 +H+ N
R C N H
H
G R O H R OH +H+ R O I R OH
OH2
H H OH2

H2N OH H3N OH OH H3N CO2H

-H+ -NH3 -H+
H H
R O +H+ R OH K R O Me H
H J

Kendall, E. C.; McKenzie, B F. Org. Synth., Coll. Vol. Ⅰ 1941, 21

Strecker amino acid synthesis, A: Protonation of the carbonyl group. B: Addition of NH3 to the
carbenyl group followed by deprotonation to form a hemiaminal. C: Protonation followed by
elimination of water is helped by the nitrogen lone pair to form an iminium ion. D: Addition of a cyanide
ion to form an aminonitrile. E: Acidic hydrolysis of the nitrile. The amino group is protonated
throughout the reaction. F: Protonation of the nitrile to form a reactive nitrilium ion. G: Addition of
water to the nitrilium ion. H: Deprotonation and tautemerization. I: Protonation of the resulting amide
followed by addition of water. J: Proton transfer. K: Elimination of NH3 followed by deprotonation to
form theproduct.

A012
O O
O
P Cl P Cl
Cl P Cl O O Cl
Cl
O Cl
Cl Cl Me Me
Me A B
H N H N H N
Me Me Me

Cl Cl Cl
Me H
H N Me -H + Me
N N
Me C Me Me
Me2N Me2N Me2N
 H H
H2O O
H2O -H+
Me Me Me
R N R N R N
D E F
Me Me Me

H O
OH H OH O
+H+ -H+
Me Me H
R N R N R H
H
Me Me Me2N

Campaigne, E.; Archer, W. L. Org. Synth., Coll. Vol. Ⅵ 1963, 331

Vilsmeier reaction. A: The electron-rich oxygen of D MF attacks POCl 3 (oxygen of amides is generally
more reactive toward electrophiles under neutral conditions). B: Addition of chloride ion followed by
eation of a dichlorophosphate ion to form the Vilsmeier reagent. C: Addition of an electron-rich
aromatic ring to Vilsmeier reagent followed by rearomatizatien D: Elimination of chloride ion helped by
nitrogen lone pair leads to the formation of an iminium ion E: Addition of water to the iminium ion.
F: Proton transfer followed by elimination of Me 2NH.

A013
H H
Me H
O O Me2N OH -H+
NH
H H A Me H H H H B

H
Me Me
Me2N OH +H+ Me2N OH2 -H2O N

H H H H H H

H Me Me
H H N
O O O
H H -H+ H H
C

H
O O
-H+
NMe2 NMe2
D

Maxwell, C. E. Org Synth., Coll. Vol. Ⅲ 1955, 305.

Mannich reactien. A: Protonation of formaldehyde followed by addition of Me 2NH to the carbonyl
group. B: Proton transfer followed by elimination of water to form an iminium ion. C: Tautomerization
of the carbonyl goroup to form an enol. D: Attack of the electron-rich enol to the iminium ion.

A014
H
O H
MeO O NHOH -H+ HO NHOH +H+
H
A Ar H +H+ Ar H
MeO NH2OH B

H H OH OH
H2O N OH -H2O N -H+ N Ac2O
Ar H Ar H Ar H

O O H
Me
OH O O Me
N Me O Me N -H+

C O O
Ar H Ar H

O Me MeO CN
N
O D
Ar H MeO
Buck, J. S,; Ide, W. S. Org. Synth., Coll Vol. Ⅱ1943, 622
A: Addition of NH2OH to the aldehyde. B: Proton transfer followed by elimination of water to form an
oxime. C: Acetylation of the oxime. D: syn-Elimination of AcOH to form a nitrile.

A015
H Cl
N OH N O PCl4 -H + N O PCl3
PCl4
OMe Cl A OMe OMe

Cl
CN Cl OMe
-POCl3 H2O
OMe NC OMe R Cl
B C
 H
H Me
OMe OMe OMe O
-H+ +H+
H
D R R O E R OH R OH
OH2 H

H
-MeOH -H+
H
R O NC O

Ohno, M.; Naruse, N.; Terasawa, I. Org. Synth., Coll. Vol. Ⅴ 1973, 266
Beckmann fragmentation. A: Attack of the oxime to PCI5. B: Elimination of POCl3 is helped by the
oxygen lone pair of the methoxy group, causing the cleavage of the C-C bond. C: Addition of chloride
ion. D: Elimination of chloride ion followed by addition of water. E: Proton transfer followed by
elimination of MeOH.

A016
EtO O EtO O MgBr aq H2SO4 EtO O H
Me Me
A
Me MgBr

H
EtO OH +H+ EtO OH2 EtO Me
Me B Me
H2O

H
H EtO -H+ EtO -H+
Me Me
O HO
C H D

H
EtO -EtOH -H+
Me O Me O Me
HO H

Woods, G. F.; Griswold, P. H., Jr.; Armbrecht, B. H.; Blumenthal, D. I.' Plapinger, R
J. Am. Chem. Soc. 1949, 71, 2028
A: 1,2-Addition of MeMgBr to the carbonyl group. B: Protonation followed by elimination of water
helped by the oxygen lone pair of the ethoxy group. C: Addition of water. D: Proton transfer followed
by elimination of EtOH.
A017
H2N NH2
Me Me H H Me H
N -H+ N NH2
O NH2
O OH
Me A Me +H+ Me
Me Me H OR B Me
Me Me Me

H H OR
Me N H B Me N H
-H2O N N
Me C Me
Me Me Me Me

Me H N H Me H OR Me
N -N2
Me B D Me Me
Me Me Me Me Me Me
Paquette, L. A.; Han, Y. K. J. Org. Chem. 1979, 44, 4014.
Wolff-Kishner reduction A: Addition of H2NNH2 to the carbonyl group. B: Proton transfer followed by
elimination of hydroxide ion to form a hydrazone. C: Deprotonation of the hydrazone. D: Elimination
of N2, an extremely good leavlng group.

A018

O H
N O -H+ N OH -OH- N
N H Ph +
A H Ph +H H Ph H Ph
H B

HO H N
OEt OEt
EtO2C C EtO2C H Ph D
O O
\

O N -H+ O N
H OH H EtO2C
Ph
EtO Ph +H + EtO Ph F
H CO2Et
HO CO2Et E CO2Et
Allen, C. F. H.: Spangler, F. W. Org. Synth., Coll. Vol. Ⅲ 1955, 37
Knoevenagel condensation A: Addition of piperidine to the aldehyde. B: Proton transfer followed
byelimination of hydroxide ion to form an iminium ion. C: Deprotonation of a malonate to form an
enolate ( pKa RO2CCH2CO2R = 13, H2O = 15.7). D: Addition of the enelate to the iminium ion. E:
Profonation of the amine and deprotonation of the malonate. F: Elimination of piperidine.

A019
O O
O H O Me O Me
Me N Me N
H H A
O O O O
OAc

O O O O
O Me -AcOH O O
Me N OAc H Ph
H B Me H C Me
O O N N

O
O
Me Ph O
N OAc
O
O H
Me Ph
D Me O Me N E
OAc
O O

O O H2O O
O O O
H2O
Me Ph Me Me
N N acetone N
OAc Ph reflux Ph

HO OH
OH OH Ph
O O O
-H+ -H+
Me Me OH
+H+ N +H+ N Me N
H H
F Ph Ph O
H

OAc
H Ph
O C N O C N
Ph H
OAc
Herbst, R. M.; Shemin, D. Org Synth., Coll, Vol. Ⅱ 1943, 1
A: formation of a mixed anhydride. B: Intramolecular attack of the amide oxygen to the mixed
anhydride to form an azlactone. C: Facile deprotonation of the azlactone (aromatization). D:
Addition the enolate to an aldehyde followed by acetylation. E: Deprotonation followed by elimination
of an enolate anion. F: Hydrolysis of the azlactone
A020

O O O O O H OH
OH
H
Ph A Ph H Ph B Ph Ph C

O OH O OH O

Ph Ph Ph Ph Ph Ph
H
HO

OH
H Ph
O C H O C H
Ph H D OH
Kohler, E. P.; Chadwell, H. M. Org. Synth., Coll Vol. Ⅰ 1941, 78
Aldol reaction. A: Deprotonation of the ketone to form an enolate. B: Attack of the enolate to an
aldhyde C: Protonation and deprotonation followed by elimination of a h ydroxy ion. D: Newman
projection.

A021
O
CO2Et OEt
H OEt O
A B C
H
CO2Et
O OEt O OEt

H3O+
O OEt O O
D H
CO2Et CO2Et CO2Et

Schaefer, J. P.; Bloomfield, J. J. Org. React. 1967, 15 14

Dieckmann condensation. A: Deprotonation of the ester to form an enolate. B: Intramolecular
addition of the enolate to the other ester, C: Elimination of ethoxide ion. D: pKa RCOCH2CO2R = 18.
EtOH = 16.
A022
H
O O N HO N N
-H+ OH
N H
H +H+
A
B

O O
N N Me O Me N O
Ac2O
C D Me
H
OAc

H
N O N O H2O N OH
aq HCl
E Me Me F Me
H

H
H H
N O N O N O
H O -2H+ HO +H+ HO H
Me H Me Me
G

H
O O O O
-H+
Me Me

Stork, G.; Brizzolara, A.; Landesman, H.; Szmuszkovicz, J.; Terrell, R.

J. Am. Chem. Soc. 1963, 85, 207.
Stork enamine reaction. A: Addition of p yrrolidine to the ketone. B: Proton transfer followed by
elimination of hydroxide ion. C: Deprotonation to form an enamine. D: Attack of the enamine to
acetic anhydride. E: Deprotonation to form a vinylogous amide. F: Protonation of the vinylogous
amide. G: Addition of water to the resulting iminium ion. H: Proton transfer followed by elimination of
pyrrolidine.
A023

O O O O O O
aq KOH
EtO OEt EtO OEt EtO OEt
H A B n-C7H15
On-Bu Br n-C6H13

O O OH O O O O
OH OH
H
EtO OEt EtO OEt EtO O
C
R R R

O O O O O O
work up
EtO O O O HO OH
+H+
R R R

H
O O OH O
-CO2 H -H+
HO O HO HO
D +H+ n-C7H15
R R
E
Reid, E. E.; Ruhoff, J. R. Org. Synth., Coll. Vol.Ⅱ 1943, 474.
A: Deprotonation of the malonate to form an enolate ( pKa ROH = 16, RO2CCH2CO2R = 13). B:
Attack of the enolate to an alkyl bromide. C: Hydrolysis of the esters. D: Decarboxylation through a
six-membered transition state. E: Tautomerization.

A024

H
O OH OH
+
H -H
Me Br Br
A
Br Br Br

H Br
O O
Br -HBr Br
B
Br Br
Langley, W. D. Org. Synth., Coll. Vol. Ⅰ 1941, 127
A: Acid-catalyzed formation of an enol. B: Bromination of the electron-rich enol.
A025

Cl PCl2 Cl
P
O Cl OPCl2 Cl O Cl
R H R R
O OH OH A

Cl
R
OH Cl
H R Cl
OH -HBr H2O
O R
O +H+
P B Br Br
Cl Cl Br

H2O
Cl HO Cl OH
-H+ -HCl
R R R
OH OH O
C
Br Br Br
Clarke, H. T.; Taylor, E. R. Org. Synth., Coll. Vol. Ⅰ 1941, 115
Hell-Volhard-Zelinsky reactlon A: Formation of an acid chloride. B: pKa CH3COCl = 16, CH3CO2R =
24. Formattion of an electron-rich enol followed by bromination. C: Hydrolysis of the acid chloride.

A026
O
Me H
Me H O O
N I
H H R I I A R
HO

O O O OH
NaOH
I I I
R R R
EtOH-H2O B C
I I I I I I
HO
O
O OH
Me
H
R O -CHI3 O workup
I Me H
R O +H +
I I H H
HO

Bergmann, E. D.; Rabinovitz, M.; Levinson, Z. H. J. Am. Chem. Soc. 1959, 81, 1239.
Idioform reaction. A: Iodination of the α-position of the ketone. B: Addition of hydroxide ion. C:
Elimination of an iodoform anion.
A027
EtOH Et H
Br Br O O O O
r-
-B
Br Br
O Me A O Me B O Me

Et H Et H
-H + O O +H+ O O -AcOH
Br Br
C O Me O Me

OEt OEt OEt

-H+
Br Br Et Br
D O OEt
HOEt H
McElvain, S. M.; Kundiger, D, Org. Synth., Coll. Vol. Ⅲ 1955, 123
A: Bromination of the electron-rich enol ester. B: Addition of EtOH. C: Proton transfer followed by
elimination of AcOH. D: Addition of EtOH.

A028
H BH2 H BH2 n-Bu C6H13
B C6H13
n-Bu A n-Bu A H
C6 13

- RO
NaOH R O OH R O OH -OH
B R B B R
aq H2O2 B R R C
R R

RO aq NaOH
B OR Me OH
RO D

Kono, H.;Hooz, J Org. Synth., Coll, Vol, Ⅵ 1988, 919

A: H ydroboration through a four-membered transition state. B: Attack of a h ydroperoxide anion to the
borane to form an ate complex, C: Migration of an alkyl group. D: Hydrolysis of the borate.

A029
O O O
OAc H H O
O O O O
C10H21
A B O
OBn R R
 Me2S
O O O
O Me2S O
Me2S
C O O D O O R
R R

OAc
Me H
+ + OHC C10H21
S
Me O O H
OBn
Ko, K.-Y.; Eliel, E. L. J Org. Chem. 1986, 51, 5353
A: 1,3-Dipolar cycIoaddition of ozone to the olefin. B: Heterolytic cleavage of the initial ozenide. C:
Recombination of the resulting 1,3-dipole and the aldehyde to form an ozonide. D: Reductive
cleavage of the O-O bond of the ozonide with Me2S.

A030
Me
Me Me
Me
Me Me O O Me O O
H
Me A B H
HO OH O OH

Me Me
-H+ Me O O Me Me O O Me Me

Me O O Me
O OH
McCloskey, A. L.; Fonken, G. S.; Kluiber, R. W.; Johnson, W. S. Org. Synth., Coll. Vol.Ⅳ 1963, 261.
A: Protonation of isobutylene to form a stable tertiary carbocation. B: Attack of a carboxylic acid to the
esterication.

A031
H2O
OAc Me OH
Me
Me
Hg Hg OAc
OAc A Hg OAc
 OH OH OH
NaBH4 Me Me Me

Hg OAc B Hg H R C Hg

H
OH HO OH
-Hg Me Me Me
H Hg D

Jerkunica, J. M.; Traylor, T. G. Org. Synth., Coll. Vol. Ⅵ1988, 766.

A :Oxymercuration of the olefin. B: Reduction with NaBH4 to form a Hg-H bond. C: Cleavage of the
Hg-H bond followed by extrusion of Hg to form a secondary carbon radical. D: Abstraction of a
Hydrogen atom.

A032
OTf
Hg -H+
HgOTf
OTf
A
H2O

H
-H + O +H+
HgOTf HgOTf
HO +H+
B
H

H
O OTf -Hg(OTf )2 OH -H+ O
Hg
OTf C +H+ Me
Nishizawa, M.; Skwarczynski, M.; Imagawa, H.; Sugihara, T. Chem. Lett. 2002, 12.
A: Oxymercuration of the alkyne. B: Tautomerization of the enol. C: Demercuration to regenerate
Hg(OTf)2.
A033
MeO MeO MeO

NH2 -H+ NH -H2O N

MeO MeO MeO
+H+ HO A I
O
I
I

MeO MeO MeO

CF3CO2H NH NH NH
MeO MeO MeO
+H+ B H
I I I

Whaley, W. M.; Go vindachari, T. R. Org, React. 1951, 6, 151.

Pictet-Spengler reaction. A: Formation of an imine. B: Addition of an electron-rich aromatic ring to
the iminium ion followed by aromatization.

A034
MeO MeO
HN Me HN Me Cl
MeO A MeO B
O Cl
Cl O Cl
Cl Cl P
P
O
O
MeO MeO MeO
-H+
Me
HN Cl HN Cl N Cl
MeO MeO C MeO
Cl
O Cl Me Me
P
O

MeO MeO MeO

N N N
D MeO E MeO MeO
H
Me Me
Me
Brossi, A: Dolan, L. A.; Teitel, S. Org. Synth., Coll Vol. Ⅵ 1988 1
Bischler-Napieralski reaction. A: Attack of the o xygen atom of the amide to POCl 3. B: Addition of
chloride ion followed by elimination of dichlorophosphate ion. C: Deprotonation. D: Elimination of
chloride ion to form a nitrilium ion. E: Attack of an electron-rich aromatic ring to the nitrilium ion.
A035

H
Cl Cl O O
Cl OH Cl
HO H Cl Cl C C
A Cl B Cl
Cl Cl

H OH
O O OH O Cl O Cl
H H
CCl2 CHCl2
Cl
C D E F OH

H OH
O O O O OH O
workup
Cl H H
G H +H+

Wynberg, H.; Meijer, E. W. Org. React. 1982, 28, 1.

Reimer-Tiemann reaction. A: Deprotonation of CHCl 3 followed by α-elimination to form di-
chlorocarbene ( pKa CHCl3 = 13.6, H 2O = 15.7). B: Formation of phenoxide ion ( pKa PhOH = 10).
C: Attack of the phenoxide ion to dichlorocarbene. D: Protonation. E: Aromatization. F: Elimination
of chloride ion helped by the o xygen lone pair of the phenoxide ion. G: Conjugate addition of
hydroxide ion. H: Elimination of chloride ion.

A036
H2C CH2
Cl AlCl3 -AlCl4- O
O
O A B
MeO MeO MeO H2C

O O

C MeO MeO
H

or
H2C CH2
Cl AlCl3 -AlCl4- O
O
O A B
MeO MeO MeO H2C
 O

O O

D MeO E MeO MeO

H
Sims, J. J.; Selman, L. H.; Cadogan, M. Org. Synth, Coll. Vol. Ⅵ 1988, 744
Intramolecular Friedel-Crafts acylation. A: Formation of an acylium ion. B: Addition of ethylene to
the aeylium ion. C: Attack of the aromatic ring to the resulting primary carbocatian. D: Attack of the
aromatic ring at the para position of the methoxy group to the primary carbocation. E: 1,2-Alkyl shift.

A037
N H H2
N O O HCl NH2 N N N O
HO O O O OH N
A N B
H H2O O CO2H CO2H

H H
-H+ N OH N OH -H+ N OH2
N N N
+H+ +H+
C CO2H CO2H CO2H

NMe2 NMe2
N
N N N
N N
D H E
CO2H NMe2 CO2H OH2 CO2H
Clarke, H. T.; Kimer, W. R. Org. Synth., Coll. Vol.Ⅰ 1941, 3. 4,
A: Formation of nitrous anhydride. B: Addition of the aniline to nitrous anhydride. C: Proton transfers
fallowed by elimination of water to form a diazonium salt. D: Addition of electron-rich dimethylaniline
to the diazonium salt. E: Aromatization.

A038
Na/NH3 e H OEt
Me Me Me
A B
Me Me Me
 H H
Me Me Me

Me Me Me

H OEt
e

Me Me Me
>
C
Me Me Me

Paquette, L. A.; Barrett, J. H. Org. Synth., Coll. Vol. Ⅴ 1973, 467.

Birch reduction. A: Single electron transfer (SET) from Na to the aromatic ring to form a radical anion.
B: Protonation. C: More substituted olefins are formed because alkyl groups destabilize a carbanion.

A039
OMe O OMe O OMe O OMe O
H NH2
O O O O
A B H
e H
H NH2 e

OMe OMe OMe H

CO2 C7H15Br CO2 C6H13 CO2 H3O+
C D C7H15
Br

H
OMe OMe HO O Me
CO2H H2O CO2H -H+ CO2H
H
C7H15 E C7H15 +H+ C7H15 G
F

H H H
O O O O O
CO2H -H+ C7H15 -H+ C7H15
O
C7H15 C7H15 H +H+
I
H
 Taber, D. F.; Gunn, B. P.; Chiu, I.-C. Org. Synth., Coll Vol.Ⅵ 1983, 249.
Birch reduction A: Single electron transfer (SET) to form a radical stabilized by the carboxylate. B:
Protonation of the radical anion, C: SET to form a dianion species. D: Alkylation of the dianionic
species. E: Protonation of the electron-rich enol ether. F: Addition of water followed by proton
transfer. G: Elimination of MeOH. H: Decarboxylation through a six-membered transition state.
I: Tautomerization.

A040
O
O N
H Na O
MeO H
A O F
O OMe
MeO

O OMe

O O
N N
O O
B F C MeO2C
MeO2C
CO2Me CO2Me

Selvakumar, N.; Reddy, B. Y.; Azhagan, A. M.; Khera, M. K.; Babu, J. M.; Iqbal, J
Tetrahedron Lett. 2003, 44, 7065
A: Deprotonation of the malonate to form an enolate ( pKa RO2CCH2CO2R = 13, H2 = 35), B:
Nucleophilic addition of the enolate to the electron-deficient aromatic ring. C: Elimination of fluoride
ion.

A041
Br Br
P Me H Me
Me H
Br O Br Br
O Me P Me
Me A B
Br
Br
Noller, C. R.; Dinsmore, R. Org. Synth., Coll. Vol. Ⅱ 1943, 358
A: Attack of the alcohol to PBr3. B: SN2 reaction.
A042
H2O OH
O O O
Cr Cr OH
O A O

OH
O H
Cr OH -H2O O O
O Cr
OH B O OH

H
+H+ O OH O
Cr
O OH C

Eisenbraun, E. J. Org. Synth., Coll. Vol.Ⅴ1973, 310.

Jones oxidation. A: Hydration of CrO3. B:Attack of the alcohol to H 2CrO4. C: Elimination of H2CrO3.

A043
O
Cl O
Cl -CO2
Cl
O O -CO Cl
O Cl
S O S
S Me Me A Me Me
Me Me
Cl

Cl
Cl H NEt3
S
Me Me -HCl Me Me
S S
B R O Cl R O Me
R O
H

H CH3 -Me2S H
S
C R O Me D R O

LeopoLd, E. J. Org. Synth., Coll. Vol. Ⅶ 1990, 258.

Swern Oxidation. A: Attack of D MSO to (COCl)2 to form a chlorosulfonium ion with generation of CO
and CO2. B: Attack of an alcohol to the chlorosulfonium ion. C: Formation of a sulfur ylide. D:
β-Elimination of Me2S.
A044
O
H O I O O O
H O O HO I
HO O O O
HO O I O -H+ HO O
O
+H+
O O O O R R R R

Me Me Me Me

O O
O O H
-H2O I O
O O
2 H
A B O O
R
R R
Me Me
Schmid, C. R.; Bryant, J. D. Org. Synth., Coll. Vol Ⅷ 1995, 450
A: Formation of a cyclic intermediate. B: Cleavage of the C-C bond to form two molecules of the
aldehyde,

A045
EtO2C CO2Et
EtO2C CO2Et N N O
N N Ph3P H
A O B
Ph3P

EtO2C CO2Et EtO2C CO2Et

EtO2C CO2Et
N NH N NH
Me - HN NH
Ph3P Me
O CO2Et C Ph3P
O CO2Et
H H

O O Me
Me - Ph3P O
O O CO2Et
Ph3P
O CO2Et

Mitsunobu, O. Synthesis 1981 1

Mitsunobu reaction. A: Conjugate addition of Ph 3P to DEAD to form a zwitter ion. B: Deprotonation
to the most acidic proton in the reaction system. C: Attack of the alcohol to the activated reagent
followed by deprotonation. D: Attack of the carboxylate with inversion of configuration.
A046
Me Me
H
Br Me Br Me
O O
H A H

Me
Br Me Me Me

B Br C Br
H

Zhong, G.-F.; Schlosser, M. Synlett. 1994, 173

Wanger-Meerwein rearrangement. A: Protonation of the alcohol. B: Elimination of water assisted by
cleavage of the C-C bond to form a stable tertiary carbocation C: Deprotonation to form an olefin.

A047

H
H H
HO O -H2O

OH A OH OH

-H+
B
OH O

Walter, C. R., Jr. J. Am. Chem. Soc. 1952, 74, 5185.

pinacol rearangement. A: Protonation of the alcohol followed by elimination of water to form a tertiary
center. B: 1,2-Alkyl shift helped by the oxygen lone pair of the hydroxy group.

A048
Me Me Me
Me Me Me
A B
O O O
H H H

Me Me
-H +

C D
Me Me
H
OH OH
 Waring, A J.; Zaidi, J. H.; Pilkington, J. W. J. Chem. Soc., Perkin Trans. Ⅰ 1981, 1454.
Dienone-phenol rearrangement. A: Protonation of the ketone. B: 1,2-Alkyl shift to form a stable
tertiary carbocation. C: 1,2-Alkyl shift to form a stable tertiary carbocation. D: Aromatization by
deprotonation.

A049
Me Me Me

OH OH OH
Me A Me Me B
Me OH Me OH2 Me N C Ph

Me Me Me
H -H+
OH O O
Me C Me Me
N N Ph N Ph
Me C Me Me
Ph
Tillmanns, E.-J.; Ritter, J. J. J. Org. Chem. 1957, 22, 839
Ritter reaction. A: Protonation of the tertiary alcohol followed by elimination of water to form a more
stable tertiary carbocation. B: Attack of PhCN to the carbocation to form a nitrilium ion. C
Intramolecular addition of the hydroxy group to the nitrilium ion.

A050
O
H
Me Me -N2 Me
NC N N CN NC H SnBu3
Me Me A Me B
H
Bu3Sn Br

O O
H H

C D
H H
Bu3Sn H

Hamon, D. P. G.; Richards, K. R. Aust. J. Chem. 1953, 36, 2243

A: Thermal decomposition of AIBN to gi ve the stable tertiary radicals. B: Abstraction of a hydrogen
atom from Bu3SnH. C: The resulting tin radical reacts with a halide to form a carbon radical. D:
Abstraction of a hydrogen atom from Bu 3SnH to continue the radical chain reaction.
A051
S
H S
H O
O C H S O
H H
S I CH3
A N B
N H N
H H
Ph O
Ph O Ph O

Bu3Sn Bu3Sn
S S S

MeS O MeS O MeS O

H H H
Bu3SnH
AIBN D
N C N N
H H H
Ph O Ph O Ph O

Bu3Sn H
H H

E F
N N
H H
Ph O Ph O

Comins, D, L.; Abdullah, A. H. Tetrahedron Lett. 1985, 26, 43.

Barton-McCombie deoxygenation. A: Deprotonation of an alcohol. B: Addition of the alkoxide ion to
CS2 followed by methylation to form a xanthate. C: Generation of a tin radical. D: Attack of the
radical to the sulfur atom of the xanthate to form a stable carbon radical. E: Cleavage of the C-O bond
to form a secondary carbon radical. F: Abstraction of a hydrogen from Bu3SnH.

A052
O O O
B
N H N N
A B
Cl
O O O

O H2N NH2 O
H2NNH2 -H+ -H+
NH
N +H+ +H+
NH2
Ph C D
O O NH

Ph
 O O

NH NH H2N
+
NH NH
O NH2
O
Ph
Manske, R. H. F. Org. Synth., Coll. Vol. Ⅱ 1943, 83.
Gabriel synthesis. A: pKa RCONHCOR = 9.6, HCO3- = 10.3. B: Afkylation, C: Addition of H2NNH2
to the imide to form a hydrazide. D: Intramolecular addition of the amino group of the hydrazide to the
amide carbonyl to release benzylamine.

A053
O
H
H OH2 H O
H O -H+ HN -H2O -CO2
NH2 HN CH2
+H+ B
A

HO OH
Me Me
HN Me N Me aq H2O2 N Me

C D

H OH
O O O
NMe2 NMe2 H NMe2
E

Cope, A, C.; Bumgardner, C. L.; Schweizer. E. E. J. Am. Chem. Soc. 1957, 79, 4729
Eschweiler-Clarke methylation (A-C)and Cope elimination (E). A: Addition of the amine to
formaldehyde followed by dehydration to form an immium ion. B: Hydride transfer from a formate and
to the iminium ion with generation of CO2. C: Iteration of the same steps. D: Oxidation of the tertral
amine to form an N-oxide. E: syn-Elimination.

A054
 O Cl
H
O H O
O -H+ O
OH H O
A B
O O
Cl

O O

O + HO
C

Cl
Krow, G. R. Org. React. 1993, 43, 251.
Baeyer-Villiger oxidation. A: Acti vation of the carbonyl group by protonation. B: Addition of mCPBA
to the carbonyl group. C: 1,2-Alkyl shift helped by the o xygen tone-pair with cleavage of the peroxide
to form a lactone.

A055

OH H OH2
N N H2O
N
A B

OH O
-H+ -H+
N HN
+H+

Eck, J. C.; Marvel, C. S. Org. Synth., Coll. Vol. Ⅱ 1943, 76.

Beckmann rearrangement. A: Protonation of the oxime. B: Migration of the alkyl substituent with
simultaneous cleavage of the N-O bond.

A056
O O O
H
H H
O OH
A B C
O H OH O O OH O
 O
O H OH O workup OH
O
D O E +H+
O O O OH

Dakin. H. D. Org. Synth., Coll. Vol. Ⅰ1941, 149.

Dakin reaction. A: Deprotonation of the phenol ( pKa PhOH = 10, H2O = 15.7). B: Addition of
hydroperoxide ion to the carbonyl group. C: Attack of the electron-rich aromatic ring to the peroxide
oxygen with cleavage of the O-O bond to form an epoxide. D: Cleavage of the epoxide to restore the
aromaticity, E: Hydrolysis of the resulting formate.

A057
O O
MeO H OH O Cl OH Cl
N Ar N
H A Ar NH B H
MeO OH

O O HO H
C N O
C Ar N D N E Ar
Ar OH
Cl OH

H H H OH
N O N O -CO2 MeO NH2
Ar Ar
F
O O MeO
H OH

Buck. J. S.; Ide, W. S. Org. Synth., Coll. Vol. Ⅱ 1943, 44

Hofmann rearrangement. A: pKa RCONH2 = 17, H 2O = 15.7. B: Chlorination of the amide anion.
C: Deprotonation. D: The anion on the nitrogen atom induces migration of the aromatic ring with
cleavage of the N-Cl bond to form an isocyanate. E: Addition of hydroxide ion to the isocyanate. F:
Decarboxylation.

A058
O O O O O
OEt
Ph Ph Ph
O H NEt3 O Cl OEt O Cl
A
 N
O O N O O
N
Ph Ph
O OEt O OEt
B
N N N

O O O
-N2 C
Ph Ph Ph N
N N N N N N
C

Kaiser, C.; Weinstock, J. Org. Synth., Coll. Vol Ⅵ 1988, 910.

Curtius rearrangement. A: Formation of a mixed anhydride. B: Addition of azide ion to the mixed
anhydride occurs at the more electron-deficient carbonyl group to form an acyl a zide. C: Migration of
the carbon atom to the nitrogen proceeds with retention of configuration as N 2, an extremely good
leaving group, departs from the molecule.

A059
Me O O
-N2 Me O Me C
Me H N N
A H B H
H2O
H H
H H H H
HO
HO Me CO2H
+ Me +
-H OH -H
Me H
+H+ H +H+
C H H
H H
HO
Wheeler, T. N.; Meinwald, J. Org. Synth., Coll. Vol.Ⅵ1988, 840.
Wolff rearrangement. A: Photo-induced generation of a carbene. B: Insertion of the carbene to the
C-C bond results in a ring contraction to form a ketene. C: Addition of water to the ketene.

A060
O O O
H Cl Cl OMe
MeO
A B
 O OMe OMe
H
OMe O
C D

Goheen, D. W.; Vaughan, W. R. Org. Synth., Coll. Vol.Ⅳ1963, 594.

Favorskii rearrangement. A: Deprotonation to form an enolate. B: Formation of a cyclopropanone.
C: Addition of methoxide ion to the carbonyl group. D: Cleavage of the cyclopropane ring with
simultaneous protonation.

A061
Br Br Br
Br
Br H Ot-Bu Br
A Br B Br
Br Br

MeLi Me Br
A
Br C Br D E

Skattebel, L,; Solomon, S. Org. Synth., Coll. Vol. Ⅴ1973, 306,

A: Generation of a dibromocarbene via α-elimination of HBr, B: Insertion of the carbene to the olefin
toform a cyclopropane. C: Halogen-lithium exchange. D: Generation of a carbene. E: Insertion of
the carbene to the C-C bond to form an allene.

A062

H
B O O O
OMe OMe OMe
Br
A

O O OH
- +
OMe OMe H OMe
A H +H+
B
Allen, C. F. H; Gates, J. W., Jr, Org. Synth., Coll. Vol. Ⅲ 1955, 418
A: Allylation of the phenol. B: [3,3] Sigmatropic rearrangement (Claisen rearrangement). C:
Aromatization.
A063
H H
O +H+ O

O A O B

H
-H+
O O O
C D
Howard, W. L.; Lorette, N. B. Org, Synth., CoIl Vol. Ⅴ 1973.25
A: Protonation of an oxygen atom of the acetal. B: Elimination of allyl alcohol helped by the oxygen
lone pair of the acetal. C: Deprotonation to form an enol ether. D: [3,3] Sigmatroplc rearrangement
(Claisen rearrangement).

A064
O
CO2Me
O O CO2Me
CO2Me
O A B
CO2Me CO2Me CO2Me

Ziegler, T,; Layh, M.; Effenberger, F. Chem. Ber. 1987, 120, 1347.
A: Diels-Alder reaction. B: Retro Diels-Alder reaction.

A065
O
O -H+ OH -H2O
H Ph Ph
NH A Ph N +H+ Ph N
H OH B OH
OH

Ph Ph Ph Ph Ph
Ph N
Ph Ph Ph
N N N O
C
O OH O O
H Ph Ph
Brüning, I.; Grashey, R.; Hauck, H.; Huisgen, R.; Seidl, H, Org. Synth., Coll. Vol. Ⅴ1973, 1124
A: Addition of a hydro xylamine to the aldehyde. B: Proton transfer followed by elimination of water to
form a nitrone C: 1,3-Dipolar cycloaddition of the nitrone to stvrene (electronically, [4+2]
cycloaddition).
A066
Cl Cl
O O
-HCl
O O
H A H B C

or
Cl Cl
Cl -HCl O
O OH OH
H A D E

Schiess, P.; Barve, P. V.; Dussy, F E.; Pfiffner, A. Org. Synth., Coll. Vol. Ⅸ 1998, 28.
A: Isoerization to form an o-quinodimethane. B: Elimination of HCl to form a ketene. C: 4e
Elimination of hydrogen chloride to form a ketone.

A067
O O
H
O O

O O
Rondestvedt, C. S., Jr. Org. Synth., Coll. Vol. /V 1963, 766
Ene reaction.

A068
HO
H2O + O Se O Se O
HO

Me Me Me Me Me
HCl -H2O
OAc R R
OH A
H Se Se
Se HO OH O OH
O OH OH
 Me Me -Se O Me Me Me

R R OAc
B C
O O H O Se OH
Se
OH

O Se O H
O Ot-Bu Se O Se O
D O Ot-Bu
H

Umbreit, M. A.; Sharpless, K. B. J. Am. Chem. Soc. 1977, 99, 5526.

A: Ene reaction occurs on the least hindered olefin. B: [2,3] Sigmatropic rearrangement. C:
Elimination of the alcohol. D: Oxidation of SeO with TBHP to regenerate SeO2.

A069

PPh3
O O PPh3 O PPh3 - Ph P O CH2
CH2 3

A B C

Wittig, G.; Schoellkopf, U. Org. Synth., Coll. Vol.Ⅴ 1973, 751.

Wittig reaction. A: Addition of the ylide to the carbonyl group to form a betaine. B: Attack of the
alkoxide to the phosphonium cation to form an oxaphosphetane. C: Irreversible elimination of Ph3PO.

A070

O Br
Br Me O O -EtBr O O
OEt
A (EtO)2P OEt B (EtO)2P OEt
P(OEt)3
van der Klei, A.; de Jong, R. L. P.; Lugtenburg, J.; Tielens, A. G. M. Eur. J. Org. Chem. 2002, 3015.
Arbuzo v reaction. A: Attack of P(OEt) 3 to the reacti ve bromoacetate to release bromide ion (SN2
reaction). B: Attack of the resulting bromide ion to the ethyl group in an SN2 fashion to form a
phosphonate.

A071
O O O O O
(EtO)2P (EtO)2P O P(OEt2)
OEt OEt OEt
H OEt C
A O Na B
O
H
Na O
 Wadsworth, W. S., Jr.; Emmons, W. D. Org. Synth., Coll. Vol. Ⅴ 1973, 547.
Horner-Wadsworth-Emmons reaction. A: Deprotonation of the phosphonate. B: Addition of the
phosphonate ion to the ketone. C: Attack of the alkoxide to the phosphonate followed by elimination of
a phosphate ion to form an olefin.

A072
OH2
H H
H2N Cl N NH
CN CN
H2N S A H2N S H2N S
CN

H H
N N
NaOH
CN CN
H2N S H2N S
B OH
OH

H OH
H workup
N NH2
CN CN
+ S +H+ + HS
H2N OH H2N O
Gerber, R, E.; Hasbun, C.; Dubenko, L. G.; King, M. F.; Bierer, D. E. Org. Synth., Coll. Vol. Ⅹ2002, 475
A: Attack of the more reactive sulfur atom of thiourea to the alkyl chloride to form an isothiourea (SN2
reaction). B: Hydrolysis of the isothiourea.

A073
Na
O O O O O O
aq H2O2
Me
Me Me
H A B e
S Ph

Na H PhSe Cl

O O O O O O O O
Me Me Me
Me
e
S Ph C e
S Ph e
S Ph D
O O
H H
HO OH
HO

Renga, J. M: Reich, H. J. Org. Synth., Coll. Vol. Ⅵ 1988.23

A: Deprotonatien of the β-diketone ( pKa RCOCH2COR = 9, H2 = 35). B: Selenylation at the α-position.
C: Oxidation of the selenide to form a selenoxide. D: β-Elimination.
A074
BrMgO SiMe3 OH SiMe3
O workup
MgBr A +H+
H2C SiMe3

Na H Na
H
NaH O SiMe3 O SiMe3 -Me3SiO-

B C

Ager, D. J. Org. React. 1990, 38, 1.

Peterson olefination. A: Addition of Me3SiCH2MgBr to the ketone. B: Exchange of the counter
cation from Mg to Na. C: Elimination of a silanol ion via a four-membered transition state.
A075
H Me
H
H Me NEt2
- -AcOH
AcO Pd OAc AcO Pd NEt2 AcO Pd H Pd(0)Ln
A B C
Et3N
Reduction of Pd(OAc) 2 to Pd(0) using Et3N. A: Ligand exchange. B: β-Elimination. C: Reductive
elimination of AcOH.

Me Me CO2Me
Br
Me Me PdLn

Br

D Me Me E

Me Me

Me Me

CO2Me
Pd(0)Ln H
PdLn
Br
Me Me

Me Me
F
G CO2Me
HBr Br
H PdLn
Me Me
 Patel, B. A.; Ziegler, C. B.; Cortese, N. A.; Plevyak, J. E.; Zebovitz, T. C.
Terpko, M.; Heck, R. F. J. Org. Chem. 1977, 42, 3903.
Heck reaction. D: Oxidative addition. E: Carbopalladation. F: β-Elimination to form the product. G:
Reductive elimination of HBr.

A076

Pd(OAc)2 AcO OAc AcO OAc AcO OAc

+ Pd Pd Pd
2Ph3P Ph3P PPh3 Ph3P PPh3 Ph3P PPh3

Me

AcO OAc AcO O O O PPh3

Pd PPh3 Pd PPh3 Ph3P Pd(0) +
Ph3P Ph3P
Ac2O

Reduction of Pd(OAc)2 to Pd(0) using Ph3P.

OH
(HO)2B (HO)3B

Activation of boronic acid,

OHC Br

Br
Pd(0)Ln OHC PdLn

C B (HO)3B

OHC PdLn
OHC

BrB(OH)3

Huff, B. E.; Koenig, T. M.; Mitchell, D.; Staszak, M. A. Org. Synth., CoIl Vol. Ⅹ2002, 122
Suzuki-Mi yaura coupling. A: Oxidative addition. B: Transmetallation. C: Reductive elimination.
A077
2HCl + 1/2O2 O

H2O 2CuCl

PdCl2
2CuCl2
D A

O
Cl
Pd(0) Pd
Cl
O
H H

C B
O O
H
Me Pd Cl
O O
H
Tsuji, J.; Shimizu, I.; Yamamoto, K. Tetrahedron Lett. 1976, 34, 2975.
Wacker oxidation, A: Olefin complexation. B: Oxypalladation. C: Hydride shift. D: Oxidation of
Pd(0) with CuCl2 to regenerate PdCl 2. E: Oxidation of CuCl with O2 to regenerate CuCl 2.

A078
Boc Boc Boc
N N - N
LnRu R
R RuLn
A B
R RuLn

Boc Boc
N - H C RuLn N
2

C D
RuLn

Ferguson, M. L.; O'Leary, D. J.; Grubbs, R. H. Org. Synth. 2002, 80, 85.
Ring closing metathesis (RCM). A: C ycloaddition of a ruthenium carbene complex to the olefin to from
a metallacyclobutane. B: Retro cycloaddition. C: Intramolecular cycloaddition of the ruthenium
carbene complex. D: Retro cycloaddition to regenerate a ruthenium carbene complex.
解答 中级编
B001
O OH
OH OH2
H -H+ NHMe -H+ +H+
NH2 N Me N Me
+H+ +H+
Me A
CHO OH OH
O H

HO2C
OH
HO2C CO2H CO2H
-H2O -H+ -H2O
MeN O MeN O
N Me +H+ H
B CO2H CO2H
H2O
OH

O
H
CO2H O
-H+ -H+ H -CO
2
MeN OH MeN O MeN OH
+H+ C D
CO2H CO2H CO2H

-H+ -CO2 -H+

MeN O MeN OH MeN O
+H+ H D +H+
O H
O
Cope, A. C: Dryden, H. L.: Howell, C. F Org. Synth., Coll. Vol. Ⅳ 1963, 816
Robinson-Schöpf reaction. A: Formation of a cyclic hemiaminal. B: Mannich reaction C:
Intramolecular Mannich reaction. D: Decarboxylation through the six-membered transition state.

B002
Al(Oi-Pr)3 i-PrO Oi-Pr O
Al -
O O O
Ph Me Me
Me
H
A Me B

Al(Oi-Pr)2
O OH
Ph aq HCl
H

Wilds, A. L. Org. React. 1944, 2.

Meerwein-Ponndorf-Verley reduction. A: Formation of an ate complex. B: H ydride transfer via a six
membered transition state with formation of acetone.

B003
H H
O H O HO NHNH2
+H+ NH2NH2
O O O

H2N H2N
H2O NHNH2 N H N
-H+ -H2O
+H+ O -H+ O O H

N
N H H
-H+ -N2
A B
OH OH
Wharton, P. S.: Bohlen, D. H. J. Org. Chem. 1961, 26, 3615.
Wharton rearrangement. A: Cleavage of the epoxide helped by the nitrogen lone pair of the
hydrazone. B: Elimination of N2 (an extremely good leaving group).

B004

HO
HOO O
-OH-
O
A
O O O

ArSO2NHNH2 O aq K2CO3 O
H B
-H2O N NH N N
SO2Ar SO2Ar

O
O -N2
-ArSO2-

D E
N N
S Ar
O
O
 Reese, C. B.; Sanders, H. P. Synthesis 1981, 276.
Eschenmoser fragmentation. A: Michael addition. B: Formation of an epoxide (the O-O bond is
activated). C: Formation of a hydrazone. D: pKa HCO3- = 10.3, ArSO 2NH2 = 8.5. E: Fragmentation
involving a loss of N2 and a sulfinate ion.

B005

O O OH
H
CN
H CN CN
A B
N CN N N

H
O O O
-CN-
CN CN CN
CN C CN D
N N N

Stetter, H.; Kuhlmann, H.; Lorenz, G. Org. Synth., Coll Vol. Ⅵ 1988, 866
A: Formation of the less favored cyanohydrin carbanion. B: Michael addition. C: Regeneration of the
cyanide ion (cyanohydrin is unstable under basic conditions).

B006
Me Bn
Me Bn N Me Bn
N Cl N
HO S O
HO S H A HO S
NEt3 H H
Me
Me
O
Me O
Me Bn O Me Bn
N N
Me
OH
B HO S HO S H
C O
Me Me
Me O
Me Bn Me Bn
N O
N
HO + Me Me
S D HO S
O O
Me
Stetter, H.; Kuhlmann, H.; Haese, W. Org. Synth., Coll. Vol.Ⅷ 1993. 52
Stetter reaction. A: pKa thiazolinium ion = 10, HNEt3+ = 10.7. B: Generation of a stabilized carbanion
( ref B005). C: Michael addition. D: Regeneration of the thiazolinium ion.
B007

O O O O O O
O O
H OAc
Me O Me O H O O
A B
O
Me

H OAc
O O O
O O
O O O
Me O O Me O Me
C OAc O O AcO O O
O Me Me

O aq HCl O -AcOH O
O O O
D O O O O OH

Me H2O Me

Rajagopalan, S.; Raman, P. V. A. Org. Synth., Coll. Vol. Ⅲ 1955, 425.

Perkin reaction. A: pKa (CH3CO)2O = 13.5, AcOH = 4.8 (a small amount of the acetic anhydride anion
can be formed). B: Intramolecular acyl transfer. C: Formation of a mixed anhydride. D:
Base-catalyzed elimination of acetic acid.

B008
O O MeO H O
HO H Me
Me Me O
A Me B
O O O Me
O

O O O
Me N Me
H -H+
Me
benzene +H+
reflux Me N
O O H
O
 O O O
Me Me Me

HO C
N Me N N
O O O
H
OH

O O O
Me Me HO Me
H

N N N
O OH
H

O O O
Me H Me Me
HCl aq HCl H2O

N N N

O O
-H+ Me -H+ Me

+H+ HO
N O
H

Ramachandran, S.; Newman, M. S. Org. Synth., Coll. Vol. Ⅴ 1973, 486

Robinson annulation. A: pKa RCOCH2COR = 9, H2 O = 15.7. B: Michael addition. C: Formation of
an enamine followed by an intramolecular addition to the ketone.

B009

O O H O

MeO2C OMe MeO2C OMe Ph OMe

A O
H H O
OMe
Ph O OMe

O O
Ph H Ph H Ph H
OMe OMe CO2Me
B O H O O
O
O OMe O
 O O
workup
Ph OMe Ph OMe
C +H+
O
CO2H
OMe
Johnson, W. S.; Daub, G. H. Org. React. 1951. 6
Stobbe condensation. A: pKa CH3CO2R = 24, MeOH = 15.5. B: Formation of a five-membered
lactone. C: Elimination of the carboxylate occurs by avoiding the steric repulsion between the phenyl
and the methoxycarbonyl groups.

B010
Me O Me O
H H3C N N
Ph O H2C N N A Ph O

-N2 Me O

B Ph OMe

Black, T. H. Aldrichimica Acta 1983, 16, 3

A: pKa CH3CO2H = 4.8, CH3N2 = 10.2. B: The SN2 reaction occurs in a solvent cage.

B011
OTs
OTs OTs

O
O O

e e
Li/NH3

OTs
workup
+H+
O O O O
H

Stork, G.; Tsuji, J. J. Am. Chem. Soc. 1961, 83, 2783.

Two successive SET reactions followed by cyclopropane formation.
B012
CN CN CN

H A B
Cl Cl
NH2 H

NH2

CN CN

H NH2

Skorcz, J. A.; Kaminski, F. E. Org. Synth., Coll. Vol. Ⅴ 1973.263

A: pKa CH3CN = 25, NH3 = 35. B: Formation of benzyne followed by an intramolecular nucleophilic
addition.

B013
NaNO2
HCl CuCl
NH2 N N N N
A
e
CuCl2
B

-CuCl Cl
C D
Cl CuCl
Ropp, G. A.; Coyner, E. C. Org. Synth. Coll, Vol.Ⅳ 1963. 27
Meerwein arylation. A: Formation of a diazonium salt ( ref A037). B: SET induces a loss of N2 to form
a phenyl radical. C: Addition of the phenyl radical to butadiene to form a stabilized radical. D:
Recycle of CuCl to continue the radical chain reaction.

B014

H
H CyHN Me
O O S
Cy N C N Cy N C N Cy
A Cy S CyN Me
Me Me Me
O
H Me
 Me
Me
-H + CyHN Me O -Me2S
S Me O
O + Me
+H+ CyHN Me H C
H
B B

or
Me Me
Me
Me O Me O -Me2S
S Me S Me O
C Me
H CH2 H
H H
B

Tidwell, T. T. Org. React. 1990, 39, 297.

Pfitzner-Moffatt o xidation. A: Activation of DCC by protonation. B: Nucleophilic substitution at the
sulfur atom. C: β-Elimination of dimethyl sulfide might proceed either by 1) direct deprotonation with a
base or 2) formation and collapse of a sulfur ylide.

B015

H HO H2O -H2O H

A
Br
H

Br
H
H B Br
Ferreri, C.; Ambrosone, M. Syn. Commun. 1995, 25, 3351.
A: Generation of a carbocation stabilized by a cyclopropyl group. B: Cleavage of the cyclopropane
ring occurs by avoiding the steric repulsion to form the trans-product.

B016
OTs
H H
OTs

H
O O O
H
Ot-Bu
Wharton, P. S.; Hiegel, G. A. J. Org. Chem. 1965, 30, 3254.
Grob fragmentation. This Grob fragmentation can occur when the orbitals of the breaking C-C o-bond
and C-OTs σ-bond overlap on the same plane (antiperiplanar interaction).
B017
Me
AIBN Me Me
n-Bu3SnH n-Bu3Sn I
A

Me Me Me H Me
Me Me
B C
H H

n-Bu3Sn H
Me H Me -n-Bu3Sn Me H Me
Me Me
D
H H H H
Weinges, K.; Reichert, H.; Huber-Patz, U.; Irngartinger, H. Lieb igs Ann. Chem. 1993, 403.
A: Generation of a tin radical ( ref A050). B: Attack on the iodide to initiate the radical chain reaction.
C: 5-exo-trig Radical cyclization. D: 5-exo-dig Radical cyclization.

B018

O O O

Ph O O Ph A Ph O H CCl3 B
CCl3

CCl3 CCl3
-CCl3

C
CCl3
Cl3C H
Dowbenko, R. Org. Synth., Coll Vol. Ⅴ 1973, 93.
A: Homolytic cleavage of dibenzoyl peroxide. B: Generation of a trichloromethyl radical which then
adds to 1,5-cyclooctadiene. C: Transannular radical cyclization.

B019
Ph
Ph Cl -PhCH2Cl
N N O Me N O Me
A B
Cl O Me O Cl O Cl
O Cl
 MeOH -Cl- -H+
N O Me N O Me
reflux C +H+
O Cl O
HOMe
-CO2
N O Me N O NH HCl
D E
O OMe OH
H

Yang, B. V.; O'Rourke, D.; Li, J. Synlett. 1993, 195.

A: Acylation of a tertiary amine. B: Attack of chloride ion on the benzylic position. C: E1 elimination
ofthe chloride followed by addition of methanol, D: Elimination of the carbamic acid helped by the
oxygen lone pair of the methoxy group. E: Decarboxylation.

B020
Me
I Si Me Me
Me Me
Me Si
I
O O O O
Me Me -MeI
C5H11 N C5H11 N
CO2Me A CO2Me B

Me Me
Me Me Me Me
Si Si
O O O O
e
MeOH M OH -Me3SiOMe
C5H11 N C5H11 N
CO2Me C CO2Me

O OH
-CO2 H
C5H11 N C5H11 N
CO2Me CO2Me

Laurent, P.; Braekman, J.-C.; Daloze, D. Eur. J. Org. Chem. 2000, 2057.
A: Sil ylation of the electron-rich oxygen of the carbamate. B: Demethylation by SN2 reaction. C:
Methanolysis of the silyl carbamate.

B021
EtO2C O EtO2C O
PdLn
N O N O PdLn A
 Et
NHEt2 H
EtO2C O EtO2C O N Et
N O Pd N O +
B
Ln LnPd

-PdLn EtO2C
-CO2
NH + NEt2

Genet, J. P.; Blart, E.; Savignac, M.; Lemeune, S.; Lemaire-Audoire, S.; Bernard, J. M.
Synlett 1993, 680.
A: Formation of a π-allylpalladium complex. B: Attack of Et2NH to the π-allylcomplex.

B022
Ph Ph O2N
O O O O
O O N O O N - PhS
S S
N N
A S B
Ph

MeO MeO

PhS H
PhS
B

Ph Ph Ph

O O
S S -SO2
N O H SPh N O NH
H

MeO MeO MeO

Kurosawa, W.; Kan, T.; Fukuyama, T. Org. Synth., Coll. Vol. Ⅹ 2004, 482.
A: Addition of a thiolate ion to the electron deficient aromatic ring to form a Meisenheimer complex. B:
Elimination of an amidosulfurous acid anion which, upon protonation and extrusion of SO2 , gi ves an
amine.

B023
O O
BF3-Et2O
O O BF3
Me Me
Me Me Me Me
 O BF3 O
O CHO
A B Me
Me Me
Me
Me Me
Ryerson, G. D.; Wasson, R. L.; House, H. O. Org. Synth., CoIl Vol.Ⅳ1963, 957.
A: Cleavage of the epoxide to form the more stable tertiary carbecation (formation of a carbocation next
to a carbonyl group is unusually difficult). B: Wagner-Meerwein-type rearrangement.

B024
OH
O Me H
Me S N Me N N OH H2C N N H2C N N
A B
O N O
H OH
OH
O O
O -N2
H2C N N N N
C

de Boer, T. J.; Backer, H. J. Org. Synth., Coll Vol.Ⅳ1963, 225.

A: H ydrolysis of N-methyl-N-nitrososulfonamide. B: Formation of diazomethane. pKa CH3N2 = 10.2,
H2O = 15.7. C: Addition of diazomethane to a ketone followed by ring expansion (cf. Tiffeneau-
Demjanov rearrangement).

B025
Me

NC CN Me NC
Me Me
Me H
Me CN H e
M
Me A B

Kametani, T.; Kondoh, H.; Tsubuki, M.; Honda, T. J. Chem. Soc., Perkin Trans. Ⅰ 1990, 5.
A: 4e Conrotatory electrocyclic reaction to form an o-quinodimethane. B: Intramolecular Diels-Alder
reaction.
B026
FeCl3
FeCl3 FeCl3
O O O

A
SiMe3 SiMe3 SiMe3

O FeCl3 O FeCl3

B C
H SiMe3
SiMe3
X

O FeCl3 O
workup

H H
Jones, T. K.; Denmark, S. E. Helv. Chim. Acta 1983, 66, 2397.
Silicon-directed Nazarov reaction. A: Acti vation of the carbonyl group with FeCl 3, a Lewis acid. B: 4e
Conrotatory electrocyclic reaction. C: Desilylation to form the olefin regioselectively.

B034
hv
3O 1O
2 2
A

1O
O
O 2 O Et3N
O B

O
O O OH
+H+
H
C

Et3N O O

Balci, M. Chem. Rev. 1981, 81, 91.

A: Generation of singlet oxygen. B: Diels-Alder reaction. C: Base-induced cleavage of the
endoperoxide.
B035
hv
3O 1O
2 2
A

O O
1O Ph3P
O 2 O O
O B Ph3P

O
- Ph3P O O

O
PPh3

Balci, M. Chem. Rev. 1981, 81, 91

A: Generation of singlet oxygen. B: Diels-Alder reaction. C: Reductive cleavage of the endoperoxide
with triphenylphosphine. D: Formation of an epoxide via SN2' reaction with elimination of
triphenylphosphine oxide.

B041

CrCl2
Me Br CrCl2 Me
A

Me CrCl2 Ph
Ph Me O
O CrCl2 B
H
H
Ph OCrCl2 OH
workup
Me O
CrCl2 Ph +H+ Ph
H Me Me
Okude, Y.; Hirano, S.; Hi yama, T.; Nozaki, H. J. Am. Chem. Soc. 1977, 99, 3179.
A: Since CrCl2 is a single electron reductant, two molecules of CrCl 2 are needed to convert an alkyl
bromide to the corresponding organochromium species. B: Addition to an aldehyde via a chair-like
six-membered transition state.
B042
O

n-Bu n-Bu
H n-Bu
H
HRh(CO)L2 L2 Rh
A
E CO B

O n-Bu
H n-Bu
L2 Rh H L2 Rh
CO CO
O
D n-Bu CO n-Bu
CO
L2 Rh L2 Rh
CO C CO
H2
Hallman, P. S.; McGarvey, B. R.; Wilkinson, G. J. Chem. Soc. (A) 1968, 3143.
Hydroformylation. A: Complexation of the catalyst with an olefin. B: Hydrometallation. C: Insertion

B045
N N
C
O O S O S
H A B
SCN H H
Ph Ph Ph

N
C
O S Ph S S
H
Ph
H C
Ph O H
C
N
Guss, C. O.; Chamberlain, D. L., Jr. J. Am. Chem. Soc. 1952, 74, 1342.
A: Cleavage of the epoxide by SN2 reaction at the less hindered position. B: Migration of the cyano
group. C: Intramolecular SN2 reaction with inversion of configuration.

B046
Me Me
O HO NMe2 N
-H+ HO
H
Me Me Me Me
HN +H+
MeO OMe Me MeO OMe MeO OMe
 Me Me Me Me Me Me
N N N
-MeO - -H +
Me Me Me
A B
MeO OMe MeO Me MeO NMe2
HN
Me

Me Me HO NHMe2 O
N
-MeO - OH2 - + -MeO -
H Me Me
Me
+H + -H +
Me2N Me2N
Me2N

Kozmin, S. A.' He, S.; Rawal, V. H. Org. Synth., Coll. Vol. Ⅹ 2004, 301.
A: Formation of an enamine to eliminate methoxide ion. B: Conjugate addition of dimethylamine to the
α,β-unsaturated iminium ion.

B047
H
Me Me Me Me
Me Me N N H
N -MeO- -H+
H OMe N OMe N OMe
A N +H+ B
MeO OMe

N
OBn H OBn OBn
H OMe
N -MeO-

O C O OMe
N N NO2
O O

MeO H
OBn H OBn Raney Ni OBn
N -H+ N NH2NH2 N
D E
NO2 NO2 NH2

OBn H OBn OBn

-MeO- N -H+
F +H+ H
NH2 N N N N
H H H
 OBn OBn
- N
H H -H+

G
N N
H H
Batcho, A. D.; Leimgruber, W. Org. Synth., Coll. Vol.Ⅶ 1990
Leimgruber-Batcho indole synthesis. A: Generation of an iminium ion under thermal conditions. B:
Replacement of dimethylamine with pyrrolidine. C: Generation of a benzylic carbanion stabilized by
o-nitro group. D: Formation of an enamine. E: Reduction of the nitro group. F: Protonation of the
enamine to form the reactive iminium ion. G: Elimination of pyrrolidine helped by the nitrogen lone
pair.

B048
ArO2S NC

ArO2S NC O C
O
N
H
A B
t-BuO K SO2Ar

H OEt
H
O N
O O
N N
H OEt SO2Ar
SO2Ar SO2Ar H OEt

H OEt

N OEt N
O O
Ar -ArSO2- CN
SO2Ar S
C O O

Oldenziel, O. H.; Wildeman, J; van Leusen, A. M. Org. Synth., Coll. Vol Ⅵ 1988, 41.
TosMIC (p-toluenesulfonylmethyl isocyanide). A: Deprotonation of an active methylene compound.
B: Intramolecular addition to the isocyanide to form an oxazoline anion. C: Loss of the activated formyl
group with a concomitant elimination of a toluenesulfinate ion ( pKa PhSO2H = 1.5).
B049
Ph3P Br
O
Br Br O
Ph3P Br C Br Br C H n-C7H15 Br
A Br n-C7H15
Br Br
Br

Li
PPh3
O n-Bu
Br Br BuLi Br
Br n-C7H15 n-C7H15 n-C7H15
B
Br Br Br
Ph3P

H Li
Li -LiBr
n-C7H15 n-C7H15 n-Bu H n-C7H15
C Br D

workup
Li n-C7H15 H n-C7H15
D +H+
Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 13, 3769
Corey-Fuchs reaction. A: Generation of a stable carbanion (cf. pKa CHCl3 = 13.6). B: E2 elimination
(triphenylphosphine oxide is an extremely good leaving group). C: Halogen-lithium exchange follow by
α-elimination to generate an alkylidene carbene. D: C-H insertion of the carbene. E: pKa n-Bu = 50,
-

RC≡CH = 25.

B050
Me ArSO2NHNH2 Me Me
O N SO2Ar BuLi N SO2Ar
Me Me N Me N
H
-H2O H
Me Me A Me Me Me Me
n-Bu Li
O O
Me Me -SO2Ar Me
N SO2Ar N S N
Me N Me N Ar Me N
B
H
Me Me n- u Me Me Me Me
B Li

O Ph Ph Ph Ph
-N2 Me Me workup Me
Me Ph Ph Me O Me OH
C +H+

Me Me Me Me Me Me
 Rupert, K. C.; Liu, C. C.; Nguyen, T. T.; Whitener, M. A.; Sowa, J. R.. J,
Organometallics 2002, 21,144
Shapiro reaction. A: Formation of a hydrazone. B: Deprotonation of the α-position of the hydrazone
anion. C: Elimination of a sulfinate ion ( pKa RSO2H = 1.5). D: Loss of N2 to form an alkenyl anion.

B051
H H H -CO2
O O O -H+ H
O O O
OH
Ar OH Ar OH A Ar OH B Ar

-H+ H HO CO2Me -H2O HO CO2Me

Ar +
+H+ NH2 +H+ N
O HO HO H

Ar

+H+ HO CO2Me -H+ HO CO2Me

C N NH
HO H HO
H
Ar Ar
Konda, M.; Shioiri, T.; Yamada, S. Chem. Pharm. Bull. 1975, 23, 1025
A: Generation of a stabilized benzyl cation. B: Decarboxylation to form an enol, an aldehyde
equivalent. C: Pictet-Spengler reaction ( ref A033).

B052
H
H O O
O H
O O OMe O O O O
H H
H H H
A B
O O O

O O O O -HCO2Me O O OH
O O
C +H+
OH
O H O HO H O
H
MeO H
MeO
Shimada, K.; Kaburagi, Y.; Fuku yama, T. J. Am. Chem. Soc. 2003, 125, 4048.
A: pKa MeOH = 15.5, CH 3CHO = 16.7. B: Aldol reaction. C: Intramolecular hydride transfer
(Cannizzaro-type reaction).
B053
O
O O O
OMe H
Me
OMe O OMe
N A Me B
N H N
N N
N

OH O OH O
-H+ Me Me
OMe OMe
+H+ C
N
N

Brown, J. M.; Evans, P. L.; James, A. P. Org. Synth., Coll. Vol. Ⅷ 1993, 420.
Morita-Baylis-Hillman reaction. A: Michael addition of DABCO. B: Aldol reaction. C: Elimination of
DABCO.

B054

N
O H N CO2Me N
O B
-H2O
A
OMe

N N
N OMe CO2Me
CO2Me
A O C

OH2
N N N
+
CO2Me aq HCl CO2Me CO2Me -H
H +H+

- H2
NH OH N O O
CO2Me H CO2Me Pd/Al2O3 CO2Me
-H+ MeOH
 Burpitt, R. D.; Thweatt, J. G. Org. Synth., Coll. Vol. Ⅴ 1973, 277.
A: Formation of an enamine. B: A stepwise formation of the four-membered ring by means of Michael
addition. C: Cleavage of the cyclobutene to release the ring strain.

B055
O O O O O O

Ph OEt Ph OEt Ph OEt

A B H
H N N N Ts N N
NEt3 N Ts

O O O O O O
-TsHN-
Ph OEt Ph OEt Ph OEt
N N C N N
N Ts
H N N
Lall, M. S.; Ramtohul, Y. K.; James, M. N. G.; Vederas, J. C. J. Org. Chem. 2002, 67, 1536.
+
Regiz Diazo transfer reaction. A: pKa RCOCH2CO2R = 11, HNEt3 = 10.7. B: Attack on the less
hindered, electrophilic nitrogen. C: pKa PhSO2NH2 = 8.5:

B056

Ts
N N
N OEt
t-BuO H
A
S S S

H OEt
Et H
OEt OEt O OEt OH2
N HN H2N
aq HCl H2N
+H+
S S B S S

H
EtO OH OH O
-H+ H3N H3N -H+ H3N
+H +
S S S

Dijkstra, D.; Rodenhuis, N.; Vermeulen, E. S.; Pugsley, T. A.; Wise, L. D.; Wikstrm, H. V.
J. Med. Chem. 2002, 45, 3022.
Neber rearrangement. A: Generation of a nitrene to form the azirine, which then undergoes addition of
ethanol. B: Acidic hydrolysis of the ethoxyaziridine.
B057
Me Me Me Me OEt
H
NaOEt
O O O O A
Br
Br Br Br Br
Br Br
Br

Me Me Me Me

OEt CO2Et
OEt
O O B
O
Br Br
Br Br

Marx, J. N.; Norman, L. R. J. Org. Chem. 1975, 40, 1602.

A: Favorskii rearrangement ( ref A069). B: Cleavage of the strained cyclopropanone with a
concurrent elimination of the bromide (formation of the thermodynamically more stable trans-ester).

B058
O O O O
I
I I I I
CO2Me A Me
O OMe O O O
H2O OMe OH H

O O O
HCl
I I I
O O B O
OH OH
O O O

O O O
OH H3C I

O O H O O O O
O O OMe

Shoji, M.; Yamaguchi, J.; Kakeya, H.; Osada, H.; Hayashi, Y. Angew. Chem. Int. Ed. 2002, 41,319;
A: Iodolactonization. B: Hydrolysis of the lactone followed by formation of the epoxide.
B059
O O
N
MeO2C MeO2C N
Cl
H

H2C N N H2C N N

Cl H3C N N ClCH3 + N2

O HBr O
N N
MeO2C N MeO2C N

O -N2 O
N
MeO2C N MeO2C Br

Br

Nair, V.; Jahnke, T. S. Tetrahedron 1987, 43 4257.

Excess diazomethane is needed to scavenge HCI.

B060
O O O O
O O
OH O O Me
Me O Me A
H
B
N N N O Me
Me Me H Me H
O

O O O O
-AcOH
O Me O Me
C OAc D
N O
N N N O
Me Me H
Me H H Me
Rueppel, M. L.; Rapoport, H. J. Am. Chem. Soc. 1978, 92, 5781.
A: Formation of a mixed anhydride. B: pKa (CH3CO)2O = 13.5. C: β-Elimination. D: Intramolecular
acylation is faster than intermolecular one.
B061
O
EtO P
CN
Me
NEt3 EtO CN R
O O
11
H R O P(OEt)2
A
Me OH O OH O O
OH O

-HCN H
R CN H2N CO2t-Bu Me N CO2t-Bu
B 11
OH O Me OH O
Shioiri, T.; Terao, Y.; Irako, N.; Aoyama, T. Tetrahedron 1998, 54, 15701.
A: Formation of a mixed anhydride. B: Formation of the reactive acyl cyanide.

B062
O O O -HCl
-POCl3
NH2 NH2 NH2
A Cl
N N N
Cl H
O Cl4P Cl O O
PCl4 PCl3
Cl

Cl4P Cl Cl
PCl3
O O -HCl
-HCl -POCl3 CN
NH2 NH
B
N Cl N Cl N Cl
Taylor, E. C., Jr.; Crovetti, A. J. Org. Synth., Coll. Vol. Ⅳ 1963, 166.
A: Activation of the N-oxide with PCl5. B: Dehydration of the amide.

B063
Cl Cl

O O
H
NC CN
O O
Me Me
OH OMe A OH OMe
Cl Cl

O O

NC CN
 O O
-H+ Me -H+ Me
OH OMe O
B
OMe
Crimmins, M. T.; Siliphaivanh, P. Org. Lett. 2003, 5, 4641.
A: Transfer of two electrons from the starting material to DDQ by forming a charge-transfer complex.
B: Deprotonation to form a p-quinonemethide-type intermediate.

B064
O
Cl S N C O H
O N O O N O
O S S
Cl O H Cl O
OMe OMe DMF OMe
O
A Me B
N H
OMe OMe Me OMe

Me Me Me
O N O N O N
O O O
O S Me O S Me O S Me
HN O N O N O CN
-SO3
OMe
OMe -H+ OMe OMe -DMF
C
OMe
OMe OMe OMe
Lohaus, G. Chem. Ber. 1967, 100, 2719.
A: Electrophilic substitution of an electron-rich aromatic compound. B: Attack on the oxygen of DMF.
C: Cyclization followed by fragmentation to form the nitrile.

B065
O O
CO2H CO2H -H+ H
O O
A +H+
NH2 N N O N N OH N N OH2
H
t-BuO N O
 O
C N C N
O
B C
N N Br Br
H OH

OH
HO O
N N -H+
N
D +H+ H
Br
Br Br
Rigby, J. H.; Laurent, S. J. Org. Chem. 1998, 63, 6742.
A: Formation of a diazonium salt ( ref A037). B: Formation of a benzvne with a loss of CO2 and N2.
C: Nucleophilic addition of the isocyanide. D: Addition of water to the nitrilium ion.

B066
AcO OAc
I
OAc
Ph
I
OH O Ph O
-AcOH -AcOH NaHCO3
-PhI MeOH
O O
A O
OH OH CbzHN
NHCbz NHCbz H O

O O
H
-H+ +H+
CO2Me
O +H+ OH B N
O
H Cbz
CbzHN OMe
O CbzN
H
O
MeO

Wipf, P.; Li, W. J. Org. Chem. 1999, 64, 4576.

A: Oxidative lactonization of N-Cbz tyrosine. B: Intramolecular Michael addition to the cross-
conjugated dienone.
B067
H
O
N C CCl3 N
H
O B O O CCl3
A

CO2Me
HO CO2Me
Me O
H H Me
NH N
TfOH -H + +
O CCl3 O CCl3 NH2
+H+ B
O CCl3

White, J. D.; Reddy, G. N.; Spessard, G. O. J. Am. Chem. Soc. 1988, 110, 1624.
A: Addition of benzyl alcohol to electron-deficient Cl3CCN with a help of catalytic amount of base. B:
Ftherification of alcohols under acidic conditions.

B068

H
+H+ -H2O
Me OH Me OH2 Me Me
Me Me A
Me Me Me

O H O O O
-H2O -H+
H C
H OH H O
H B
H

Me Me O
Me Me
- H C
Me
Me
H
C

OH2
-H+
C O OH
D
O

Koch, H.; Haaf, W. Org. Synth., Coll. Vol. Ⅴ 1973, 20.

A: Formation of a stable t-butyl cation. B: Generation of CO by dehydration of formic acid. C:
Hydride abstraction from the bridgehead of adamantane. D: Addition of CO to form an acylium ion.
B069
t-BuO
H

Ph O Ph Ph O Ph Ph O Ph
A B

Ph Ph -H+ Ph
Ph Ph
O Ph +H +
C
OH OH
Hauser, C. R.; Kantor, S. W. J. Am. Chem. Soc. 1951, 73, 1437.
[1,2] Wittig rearrangement. A: pKa PhCH3 = 41, n-BuH = 50. B: Homolytic cleavage to form a radical
anion. C: A facile radical recombination in a solvent cage.

B070
OMe
O Ph
Ph N H
H O
O A
Ph N

Ph O
C - workup
H OMe PhCN Ph Ph
O CO2Me CO2Me
+H +
N B
O O
Ph
Gómez, V.; Perez-Medrano, A.; Muchowski, J. M. J. Org. Chem. 1994, 59, 1219
A: Michael addition of an oxime anion. B: Intramolecular deprotonation to cause fragmentation.

B071
n-Bu3Sn
S n-Bu3SnS
N N
N N
O O
AIBN
n-Bu3SnH
O O
n-Bu n-Bu

Me

O O
A B H C
n-Bu OH
Me
 H Me H Me
n-Bu3Sn H - n-Bu3Sn

D
OH OH
Rawal, V. H.; Newton, R. C.; Krishnamurthy, V. J. Org. Chem. 1990, 55, 5181.
A: Barton-McCombie deoxygenation ( ref A051). B: Cleavage of the strained epoxide ring. C:
Intramolecular abstraction of a hydrogen via a six-membered transition state. D: 5-exo-trig Radical
cyclization.

B072
Br SO2CH2Br
O Br hv Me Me
Br S
A B
O SO2CH2Br
SO2CH2Br H

Br Br
-SO2CH2Br Me t-BuOK Me

C D
SO2CH2Br SO2CH2Br
H H
Ot-Bu

H Ot-Bu
CH2 -SO2

S Br
S
O O
O O
Block, E.; Aslam, M. Org. Synth., Coll. Vol. Ⅷ 1993, 212.
A: Photo-induced homolytic cleavage to form a sulfinyl radical. B: Addition to the olefin to form a
stable tertiary radical. C: Attack on the bromide of the reagent (radical chain reaction). D: Elimination
of HBr followed by vinylogous Ramberg-Bäcklund reaction.

B073
Me Me KNH2 Me Br hv Me Br
+ +
O O A O
 Br

Br Me

Me

O D C

Me

Br

Rossi, R. A.; Bunnett, J. F. J. Org. Chem. 1973, 38, 3020.

SRN1 reaction. A: SET to bromobenzene to form a radical anion. B: Fragmentation of the radical
anion to form a phenyl radical. C: Addition to enolate to form a radical anion. D: SET to continue the
radical chain reaction.

B074
S
O O
N Bu hv Bu -CO2 Bu
O N O N N
A B F3B C

O
F3B Bu N Bu
Bu O N
N N CH2
F3B S
D E

N CH2
F3B Bu

O
N Bu Bu
O N F3B Bu N N
workup
S N N
N S S
F
F3B Bu
 Newcomb, M. Ha, C. Tetrahedron Lett. 1991, 32, 6493.
A: Photo-induced homolytic cleavage. B: Decarboxylation to form an aminyl radical. C: Acti vation of
the aminyl radical by Lewis acid. D: Kinetically fa vored 5-exo-trig radical cyclization. E: Group
transfer reaction.

B075
-Br-
t-BuO H CBr3 CBr2 CBr2
A Br B

Me Me
Me
Br MeLi Br
CBr2
Br Br
Me C D
Me Me
Me

Me Me Me
Br -Br- H Me
Me
E Me
Me Me
Taylor, R. T.; Paquette, L. A. Org. Synth., Coll. Vol.Ⅷ 1990, 200.
A: pKa CHCl3 = 13.6. B: α-Elimination to form dibromocarbene. C: Cyclopropanation of the more
electron-rich, tetrasubstituted olefin. D: Halogen-lithium exchange and subsequent α-elimination to
form a carbene. E: C-H insertion of the carbene (the corresponding allene cannot be formed due to
the excessive ring strain. ref A061).

B076
Cl
O O OEt
-Cl- Cl
Cl Cl Cl
OEt OMe
Cl Cl A Cl B
Cl Cl Cl
OMe

Cl
Cl
Cl
Cl
C D
Cl Cl

Jefford, C. W.; Gunsher, J.; Hill, D. T.; Brun, P.; Gras, J. L.; Waegelt, B.
Org. Synth., Coll Vol. Ⅵ 1988, 142.
A: pKa CHCl3 = 13.6. B: Generation of dichlorocarbene. C: Cyclopropanation from the sterically less
hindered exo-side. D: 2e Disrotatory electrocyclic reaction to form an allyl cation.
B077
O
H
O O O CCl3 OH
Cl -CO2 O Cl
O H
Cl A Cl Cl Cl
Cl Cl Cl
Cl Cl
Cl

OAc OAc
Ac2O Cl Zn Cl Cl MeLi
Cl B Cl C
Cl Cl Cl
Zn

H
OMe
Cl

Cl Cl

OMe workup
H H
+H+
Wang, Z.; Campagna, S.; Xu, G.; Pierce, M. E.; Fortunak, J. M.; Confalone, P. N.
Tetrahedron Lett. 2000, 41, 4007.
A: pKa CHCI3 = 13.6. B: Reduction with Zn to form a gem-dichloroolefin. C: Corey-Fuchs-type
alkynylation ( ref B049).

B078
H SiMe3 SiMe3
O +
-H H H
H H H2O N
+H + Bn N A NHBn
Bn
H2N Bn

H
OH2 O
Me3Si
H H -H+ OH2

NHBn B NHBn +H+ NBn

OH2 OH
-H2O -H+
NBn C NBn NBn
H H
 Larsen, S. D.; Grieco, P. A.; Fobare, W. E J. Am. Chem. Soc. 1986, 108, 3512.
A: Addition of an allylsilane to the iminium ion (a silyl group can stabilize the β-carbocation). B:
Desilylation to form an olefin. C: Olefin-iminium ion cyclization to form a stable tertiary carbocation.

B079
O
O CO2Et
S
CO2Et HN N
N NH2
N N EtO2C PPh3
NO2 H
EtO2C A CO2Et B
Ph3P N N HO
EtO2C PPh3

CO2Et O
O
HN N S
EtO2C N NH2 - Ph3P O
NO2
H
O O
PPh3 PPh3

O2N -ArSO2H -N2

O S C D
N N
O H
NH2 N
H

Myers, A. G.; Zheng, B. Tetrahedron Lett. 1996, 37, 4841.

A: Mitsunobu reaction ( ref A045). B: Deprotonation of the more acidic proton. C: Elimination of a
sutfinate ion. D: Elimination of N2 via a concerted mechanism.

B080
PPh3
O O PPh3 O
PPh3
CO2Et
H CO2Et CO2Et
A
NO2 NO2 NO2

CO2Et CO2Et
P(OEt)3
O B
NO2 N
P(OEt)3
O
 CO2Et CO2Et CO2Et

O C O
N O N P(OEt)3 N P(OEt)3
O P(OEt)3

CO2Et

H D
N N CO2Et
H

CO2Et CO2Et CO2Et

A N
N N

H
N CO2Et N CO2Et
H
Mali, R. S.; Yadav, V. J. Synthesis 1984, 862.
A: Wittig reaction. B: [4+2] Cheletropic reaction and elimination of a phosphate to form a nitroso
intermediate. C: Deoxygenation of the nitroso compound to form a nitrene. D: Formation of the
indole could be interpreted as a result of either 1) a direct C-H insertion or 2) formation of the azirine
followed by homolytic cleavage and recombination of the resulting diradical.

B081
H
O O
O H
+
N N +
O N -H O -H O -H+ OH2
OH2 N N
N
OH +H+ H2N CO2H +H+ HN CO2H +H+ N CO2H
H H H
Me Me Me

H
N OH O
-H2O N -N2
H Cl CO2H
O O
H A B H
Me Me Me
Cl
Koppenhoefer, B.; Schurig, V. Org. Synth., Coll. Vol.Ⅷ 1993. 119
A: Formation of a very reacti ve α-lactone via a diazonium salt. B: Cleavage of the α-lactone with
chloride ion. The stereochemistry of the α-position is retained as a result of the double inversion.
B082
O
CO2Et
Me
MeO NaNO2 MeO Et
HCl KOH
NH2 N N
A

O
CO2Et OH
MeO Me MeO O Me
O
Et
N N B N N
Et OEt C
HO H

MeO MeO H Me
Et aq HCl -H+
N N CO2Et EtOH N N CO2Et D
H H H
65oC
Me
H
MeO Me MeO CO2Et
-H+
NH
N N CO2Et NH +2H+
H H
H
Me
MeO CO2Et MeO Me
-H+ -NH3
NH CO2Et
NH2 2 +2H+ N
H NH3

MeO Me MeO Me
H -H+

N CO2Et N CO2Et
H H
Zhao, S.; Liao, X.; Wang, T.; Flippen-Anderson, J.; Cook, J. M.
J. Org. Chem. 2003, 68, 6279.
Japp-Klingemann reaction and Fischer indole synthesis. A: Formation of a diazonium salt. B:
Addition of the enolate to the diazonium salt. C: Ketone cleavage of β-ketoester to form a hydrazone.
D: Fischer indole synthesis ( ref B031).
B083
O O Ph
N N -N2
N N C6H13
Ph Ph O
A B
B(C6H13)2 (C6H13)2B
B(C6H13)2 C6H13
C6H13

Ph workup O
C6H13 B(C6H13)2 C6H13
C O +H+ Ph

Kono, H.; Hooz, J. Org. Synth., Coll. Vol. Ⅵ 1988, 919.

A: Attack of a diazoketone to B(n-hexyl)3 to form an ate complex. B: Elimination of N2 with a
simultaneous migration of n-hexyl group. C: Formation of a boron enolate.

B084
H
O H2O OMe OMe
-H + -H+
Me Me
+H+ H
i-Bu HOMe i-Bu i-Bu

MeOH -MeOH

MeO OMe
Me

i-Bu

OMe OMe MeO OMe

I I I -H+ I AgNO3
A
i-Bu i-Bu HOMe i-Bu

HOMe
MeO OMe
OMe -H+ OMe
B C OMe MeO OMe
i-Bu i-Bu i-Bu

OH2
H2O OMe -H+
OMe
+H+ MeO OMe +H+
i-Bu OMe
D H i-Bu
 OMe OMe
HO OMe O
i-Bu i-Bu
H
Oppolzer, W.; Rosset, S.; Brabander, J. D. Tetrahedron Lett. 1997, 38, 1539.
A: Iodination of the enol ether with concomitant formation of a dimethyl acetal. B: Activation of the
iodide with a silver ion to form a phenonium ion. C: Restoration of the aromaticity causes a cleavage
of the electron-rich cyclopropane ring. D: The orthoester thus formed undergoes a facile hydrolysis to
give the ester.

B085
O O O -AcOH O
HO S OH AcO S OH S O
AcO Me A O
O O

Me Me Me Me Me Me

B
Me Me
O O OH
H H

Me Me Me Me Me Me
-H+

C
OH OH O
O SO3H SO3H
S OH
O
Bartlett, P. D.; Knox, L. H. Org. Synth., Coll Vol Ⅴ 1973, 194.
A: Generation of SO3. B: Wagner-Meerwein-type rearrangement. C: Sulfonation of the olefin to form
a stable tertiary carbocation.

B086
OMs OMs OMs
Me Me Me
NaOH
A H2O
H H H
H2B H2B (HO)3B
 H
Me
H OMs
H
Me
B
H
(HO)3B H H

Marshall, J. A.; Bundy, G. L. J. Am. Chem. Soc. 1966, 88, 4291.

A: Hydroboration from the less hindered side. B: Grob fragmentation ( ref B016).

B087
Me Me Me
Br
Br
O Br O O
Br A Br
Me Me Me
Br

t-BuO H
Me Me Me
Br
t-BuOK
O O O
Br B C
Me Me Me
H
t-BuO

Paquette, L. A.; Barrett, J. H. Org. Synth., Coll. Vol.Ⅴ 1973, 467.

A: Bromination of the olefin. B: Dehydrobromination to form a diene. C: 6e Disrotatory electrocyclic
reaction (valence isomerism).

B088

-H+ H -H+
N N
H +H+
O OH N

N
N -N2
N
N N A N B N C
H
N N N N

Golka, A.; Keyte, P. J.; Paddon-Row, M. N. Tetrahedron 1992, 48, 7663.

A: Inverse electron demand Diels-Alder reaction. B: Retro Diels-Alder reaction. C: Aromatization.
B089
O H NEt3 O O H NEt3
N N N

H Cl Cl
H
A

Cl O H OH Cl OH

O
N O N O
N
Cl
B C D

Lee, G. A. Synthesis 1982, 508.

A: Chlorination of an oxime. B: Elimination of chloride ion is facilitated by the formation of an oxime
anion. C: Generation of a nitrile oxide. D: 1,3-Dipolar cycloaddition.

B090
O O O
N Me N Me N Me
O O O
H A B H
O C NPh O N
Et3N
Ph

N Me
O O
N
C Me D
AcO AcO

or

O
O
N Me O N
O N Me
C Me
H
O N H
Ph

O +H+ -H+ O
Ph Ph N C O Ph Ph
N O -CO2 +H+ N N
H Ph NH2 H H

Mukaiyama, T.; Hoshino, T. J. Am. Chem. Soc. 1960, 82, 5339.

+
A: pKa CH3NO2 = 10.2, HNEt3 = 10.7. B: Addition of the nitronate to PhNCO. C: Formation of the
nitrile oxide might proceed either by 1) syn-elimination of the carbamate ion or 2) elimination of the
carbamate ion followed by deprotonation. D: 1,3-Dipolar cycloaddition.
B091
Me
OEt +H + OEt -EtOH OEt
H3C OEt H3C OEt H3C O
A OEt
OEt OEt H Me
H

Me H Me
CH3
-H+ EtO -EtOH -H+
+H+ EtO O EtO O B
H Me Me

Me EtO EtO Me
O R O R
EtO O C EtO O
Me Me
Me Me
Johnson, W. S.; Werthemann, L.; Bartlett, W. R.; Brocksom, T. J,; Li, T.-t.
J. Am. Chem. Soc. 1970, 92, 741.
Claisen-Johnson rearrangement. A: Acid-catalyzed ether exchange of the orthoester. B: Formation
of the mixed ketene acetal is effected by removal of ethanol from the reaction system by distillation. C:
[3,3] Sigmatropic rearrangement via a chair-like transition state to form an (E)-olefin.

B092
O OMe OMe
OH2 Me Me
Ph H -H+
Ph N
+H+ Ph N A Ph N
HN n-Pr Me OMe
n-Pr n-Pr
n-Pr Me OMe

H
MeO O H O
MeO
Me Me -H+ Me
-H+ -MeOH
Ph OH2 Ph Ph
B N +H+ N N
n-Pr n-Pr n-Pr

Overman, L. E.; Kakimoto, M.; Okazaki, M. E.; Meier, G. P.

J. Am. Chem. Soc. 1983, 105, 6622.
A: Aza-Cope rearrangement. B: Intramolecular Mannich reaction.
B093
t-Bu OTf
Si Me Me
Me Me Si
O Et3N O t-Bu OTBS
H
O O O
A

OMe OMe OMe

OMe OMe O
H H OMe
O H TBSO
O
B
TBSO OSBT

Me HO
t-Bu
H3O+ Si OMe HO2C OMe
Me O
H2O

Nakatsuka, M.; Ragan, J. A.; Sammakia, T.; Smith, D. B.; Uehling, D. E.; Schreiber, S. L.
J. Am. Chem. Soc. 1990, 112, 5583.
Claisen-lreland rearrangement. A: Formation of a ketene silyl acetal. B: [3,3] Sigmatropic
rearrangement via a boat-like transition state.

B094

Me Me O Me O
S
H Ph A S
Ph
O H O O

workup Me O 150oC Me O
H
+H + S S
Ph Ph
O O

Me
CHO
B C Me
O
Saito, M.; Kawamura, M.; Ogasawara, K. Tetrahedron Lett. 1995, 36, 9003.
A: Conjugate addition to the vinyl sulfoxide. B: syn-Elimination. C: Claisen rearrangement.
B095

Br
n-BuLi
Br S S S
A A
S S H S
n-Bu

HgCl2
S S S
H2O
S S C S
Cl Hg Cl

HgCl
-H+ S
S S
H2O S
S S CHO
Hg Hg
OH
Cl Cl
Hunt, E.; Lythgoe, B. J. Chem. Soc., Chem. Commun. 1972, 13, 757.
A: Formation of a sulfonium ion. B: Deprotonation to form a sulfur ylide, which undergoes [2,3]
sigmatropic rearrangement. C: Hydrolysis of the thioacetal.

B096
CHO CHO CHO

H B
O O Br O

H
N CO2Et CO2Et
Me
H Me
N CO2Et O N
Me -H +
H OH
+H+
O O
CO2Et CO2Et
Me CO2Et
Me Me
N H OH N N
H

A B H
O O O
Bashiardes, G.; Safir, I.; Mohamed, A. S.; Barbot, E; Laduranty, J. Org. Lett. 2003, 5, 4915.
A: Formation of an azomethine ylide. B: Intramolecular 1,3-dipolar cycloaddition.
B097
Me Me Me
AcO AcO AcO
hv
Me Me Me
AcO A AcO AcO
H H H
Me O Me O Me O
H OAc N OAc N OAc
N O O O
Cl
O N
H
O OH
AcO AcO
AcO AcO
B C
Me Me
H H
O
H N NOH
AcO -H+ AcO
D Me +H+ Me
AcO E AcO
H H
Me OH Me OH
OAc OAc
Murai, A.; Nishizakura, K.; Katsui, N.; Masamune, T. Tetrahedron Lett. 1975, 16, 4399.
Barton reaction. A: Formation of a nitrite. B: Homolytic cleavage. C: Abstraction of a hydrogen
atom via a six-membered transition state. D: Recombination of ,NO with the resulting radical. E:
Tautomerization.

B098

O O O O HO O
O N O H N O N
hv
Ph O Ph O Ph O
A B

O OH OH
O N O O N -H+
Ph O C Ph O +H+
D

O
O O N

Ph + H
O

Barltrop, J. A.; Plant, P. J.; Schofield, P. Chem. Commun. 1996, 822.

Photo-cleavable protecting group for acids. A: Photo-activated formation of a diradical. B:
Intramolecular abstraction of a hydrogen atom. C: Recombination of the diradical. D: Elimination of
benzoic acid.

B099
O
P OEt)2 O O H
O H2C ( O O O
O
A P(OEt)2 P(OEt)2
O
O O
P(OEt)2 P(OEt)2
O O
Me O Me O Me O
B

Altenbach, H.-J.; Holzapfel, W.; Smerat, G.; Finkler, S. H. Tetrahedron Lett. 1985, 26, 6329.
A: Addition to the reactive enol lactone. B: Intramolecular Horner-Wadsworth-Emmons reaction ( ref
A071 ).

B100
CHO CHO PPh3 Br
N A N B
H
H
O
O
N C N N
PPh3 PPh3

Schweizer, E. E.; Light, K. K. J. Org. Chem. 1966, 31, 870.

A: pKa of the parent indole NH = 17, H 2 = 35. B: Addition to the vinylphosphonium salt to form an ylide.
C: Intramolecular Wittig reaction.

B101
N
N PPh3 N N PPh3
PPh3
N N PPh3 N HO N
-N2
Ph Ph Ph Ph H
Ph Ph Ph
A B H Ph
OH OH OH
Ph3
P H OR H
-H+ O NH H NH2 -Ph3P=O N
Ph H H
+H+ Ph H H D
H Ph Ph3P O Ph Ph Ph
C
 Pöchlauer, P.; MüIler, E. P.; Peringer, P. Helv. Chim. Acta 1984, 67, 1238.
Staudinger reaction (A-B). A: Cheletropic reaction. B: Formation of an iminophosphorane. C:
Migration of the phosphorus group. D: Intramolecular SN2 reaction.

B102
Ph3P
H
O + O HO H HO Se
H H +H H H Ph -H+
H H Ph
Ph Ph Ph Ph A Ph Se PPh3 Ph H +H+
Ph3P Se B

PPh3 -H+
O SeH H SeH -Ph3P=O Se H -Se
Ph H
H Ph H Ph Ph D Ph Ph
Ph H Ph3P O Ph C

Clive, D. L. J.; Denyer, C. V. J. Chem. Soc., Chem. Commun. 1973, 253.

A: Acid-catalyzed cleavage of the epoxide with inversion of configuration. B: Migration of the
phosphorus group. C: Intramotecular SN2 reaction with inversion of configuration to form a cis-
episelenide. D: Spontaneous extrusion of selenium.

B103
N S N
NH S
S N N N
HO OH -H+ HO O HO O
N N N N
+H+
Ph Ph
Ph Ph Ph Ph

HN P(OMe)3
S S
N S
-H+ P(OMe)3
O O O O O O
+H+ A
Ph Ph Ph Ph Ph Ph

S P(OMe)3

O O O O -CO2

B C Ph Ph
Ph Ph Ph Ph

or
 P(OMe)3 P(OMe)3
-CO2
O O O O -P(OMe)3

C Ph Ph
Ph Ph Ph Ph
Corey, E. J.; Winter, R. A. E. J. Am. Chem. Soc. 1963, 85, 2677.
Corey-Winter olefination. A: Formation of a thionocarbonate. B: Reductive desulfurization of the
thionocarbonate to generate a carbene. C: The resulting carbene might undergo a direct
fragmentation to form the cis-olefin. Alternatively, it would react with a phosphite to form an ylide,
which then collapses to give the product.

B104
I SiMe3 Me3Si I
SiMe3
O O Me3Si O H
C8H17
H
C8H17 C8H17 A C8H17 C8H17 B C8H17 I

SiMe3
Me3Si O H
C8H17
C H D C8H17 C8H17
C8H17 I
I
Denis, J. N.; Magnane, R.; Eenoo, M. V.; Krief, A. Nouv. J. Chim. 1979, 3, 705.
A: Silylation of the epoxide. B: SN2 reaction with inversion of configuration. C: Silylation of the silyl
ether. D: E2 elimination.

B105
OMOM OMOM Me Me
C6H13 PdLn C6H13 Si Ln
O Pd H
H
O H A O Pd B
Si Si Ln C6H13 H
Me Me Me Me OMOM
Ln
MOMO Pd H MOMO H H2O2 OMOM
C6H13 -PdLn C6H13 KOH C6H13
O Si Me C O Si Me O Si OOH D
Me Me Me Me
 OMOM OMOM OMOM
C6H13 C6H13 C6H13
workup
O Si O OH E O O +H+ OH OH
Me Me Si
Me Me

Tamao, K.; Nakagawa, Y.; Arai, H.; Higuchi, N.; Ito, Y. J. Am. Chem. Soc. 1988, 110, 3712.
Tamao oxidation (D-E). A: Oxidative addition to the Si-H bond. B: Intramolecular diastereoselective
silametallation to the olefin. C: Reductive elimination. D: Formation of a silicate ion. E: Migration of
the Si-C bond.

B106
PhS Cl
Me Me Me Me
Me Me
O H O

NEt3
Me Me

Me Me Me Me Me Me
Me
O Me
SPh
A A B
Me Me Me
Me
SPh
SPh
O
O
Okamura, W. H.; Peter, R.; Reischl, W. J. Am. Chem. Soc. 1985, 107, 1034.
A: [2,3] Sigmatropic rearrangement of the propargyl sulfenate. B: 6e Disrotatory electrocyclic reaction.

B107
O O O SmI2
SmI2
MeO I SmI2 MeO I MeO
Me Me Me
O O A O

I2Sm I2Sm
O SmI2 O
OMe O

O O O
B
Me Me Me
 SmI2 SmI2
I2Sm I2Sm Me
O O HO
workup
O O O
Me Me +H+ Me
Molander, G. A.; Harris, C. R. J. Org. Chem. 1997, 62, 2944
A: Since Sml2 is a single electron reductant, two molecules of Sml 2 are needed to convert an alkyl
iodide to the corresponding organosamarium species. B: SET to the ketone followed by radical
cyclization.

B108
MeO OMe MeO OMe
Me Me

TfO
A
Hg TfOHg
TfO
Me Me

MeO OMe MeO OMe

Me Me

B C H
TfO Hg TfO Hg
H
Me Me
MeO OMe MeO OMe
Me Me

TfO D
TfO Hg
H H
Me Me
H
Imagawa, H.; lyenaga, T.; Nishizawa, M. Org. Lett. 2005, 7, 451.
A: Coordination of Hg(OTf)2 to the alkyne. B: 6-endo-dig cation cyclization to form a stable
tertiarycarbocation. C: Attack of the electron-rich aromatic ring to the carbocation. D: Protonolysis
of the C-Hg bond to regenerate the catalyst.
B109
- Ph
O O
MeO2C H MeO2C H
A

RuLn RuLn
Ph
Ph
MeO2C
MeO2C
O LnRu O
MeO2C O N N
LnRu H LnRu H H
B
R

MeO2C MeO2C
O O
LnRu N N + RuLn
H H R
R
Kinoshita, A.; Mori, M. J. Org. Chem. 1996, 61, 8356.
Intramolecular enyne metathesis ( ref A078). A: Intermolecular alkene metathesis. B: Intra-
molecular alkyne metathesis.

B110
O
CHO CHO
N A N B N C
H
SMe2
SMe2
H

O Na3N
N D N O N O E
SMe2

N3 +H+
N3 N3
N N N
O O OH

Wang, Y.; Zhang, W.; Colandrea, V. J.; Jimenez, L. S. Tetrahedron 1999, 55, 10659.
A: pKa indole NH = 17, H 2 = 35. B: Addition of the vin ylsulfonium salt to form an ylide. C:
Intramolecular addition to the aldehyde (reversible). D: Intramolecular SN2 reaction to form an epoxide.
E: Cleavage of the epoxide helped by the indole nitrogen lone pair.
B111
n=1
Ph Ph
N N N O
H N N N
O N OH N N -N2
N
O Me
Me Ph A Me Ph B
Me

n=3

N N
N N
O H N O HN
-N2
Me Ph Me
+H+
C

O
H H
O OH N
NH Me
Me Me
D NHPh
H

Wrobleski, A.; Aube, J. J. Org. Chem. 2001, 66, 886.

Intramolecular Schmidt reaction. A: Acti vation of the carbonyt group by protonation followed by
intramolecular addition of the azide (six-membered ring is easy to form). B: Ring contraction. C: The
formation of a phenonium ion is preferred over the formation of the eight-membered ring. D:
Intramolecular Mannich reaction.

B112

N O N N
Tol S S STs S S
O A H STs S B
NEt3 O S O
Tol

Et3N N N N N
S S aq HCl H S H2O S
H
S S C S S
 N N H - N O
H2O S -H+ O S H S

S +H+ S -H+ S

Woodward, R. B.; Pachter, I. J.; Scheinbaum, M. L. Org. Synth., Coll. Vol. Ⅵ 1988, 1014.
A: pKa PhSO2H = 1.5. B: Formation of an easy to form six-membered ring. C: Hydrolysis of the
enamine.

B113
Ph O Ph
Ot-Bu
H Me
O O H O O
AcN AcN O N
NAc A NAc NAc B
O O O
Ph O O Ph AcO Ph
O
Me H Ot-Bu
O Me O O
O N N HN
t-BuO H
NAc NAc NAc
O O O

AcO Ph Ph
Ph H
O H N O O
HN HN
C
NAc OAc NAc
O O

Gallina, C.; Liberatori, A. Tetrahedron Lett. 1973, 1135.

A: Deprotonation of the α-position of an imide (more acidic than amides). B: Aldol reaction followed by
an intramolecular acyl transfer via a five-membered ring transition state. C: Elimination of the acetoxy
group.

B114
O R O
H H
O OH O R O
O
-H+
Me Me C Me C O O
Me A C Me +H+
N N
Me2N R
Me Me
 Me Me Me
Me N Me N Me N
Me Me Me CSA
O O O O O B O O O toluene
R R O R

Me Me
OH Me N OH Me N
Me Me
O O C O O
H
O H O
Me Me
Me N Me N
O + Me Me
O OH O O
O
Gais, H. J. Tetrahedron Lett. 1984, 25, 273.
A: Protonation of the carbonyl group followed by addition of the carboxylate to the iminium ion. B:
Intramolecular acyl transfer to form a vinylogous anhydride. C: Acti vation of the vin ylogous anhydride
by protonation resulted in the formation of the macrocyclic lactone.

B115
OEt OEt OEt OEt
O O e
e O O
O A O B
O
OEt OEt EtO O

OEt OEt e
O O
Me3Si Cl
O O C
O O
O O

O SiMe3 O SiMe3 O SiMe3 OSiMe3

e
D
O O O Me3Si Cl OSiMe3

Bloomfield, J. J.; Nelke, J. M. Org. Synth., CoIl Vol. Ⅵ 1988, 167.

Acyloin condensation. A: Single electron transfer (SET) to the carbonyl group followed by
lactonization. B: SET followed by a ring contraction. C: SET followed by silylation. D: SET to form
an enolate followed by silylation.
B116
O O O -H+
O O +H+
A B
O O O C
O
MeOH
H H H
O O O
TsOH -H+
O O
HO H HO H +H+ R OMe
D
OMe OMe MeOH

MeOH
OMe
-H+ NaHCO3
O
R OMe HO OMe
Me2S
OMe E

Me2S -H+ OMe

O R HO R -MeOH
HO O
+H+ OMe
OMe OMe
F H
Claus, R. E.; Schreiber, S. L. Org. Synth., CoIl Vol. Ⅶ 1990, 168.
A: 1,3-Dipolar cycloaddition of ozone to the olefin. B: Heterolytic cleavage of the initial ozonide. C:
Trapping the dipole with methanol. D: Formation of a dimethyl acetal from the aldehyde (protonation
of the less electron-dense hydroperoxy group is more difficult). E: Neutralization to kill TsOH. F:
Reduction of the hydroperoxide with dimethyt sulfide.

B117
O O O -H+
O O +H+
A B
O O O C
O
MeOH
NEt3
O O
O Ac2O O H
H OH H O
Et3N
OMe OMe

O O
NEt3
Me O Me O O
H
R O R O O
O O Me H
D E
OMe OMe OMe

or
 NEt3
O H O
H
R O R O O
O Me H
E
OMe OMe OMe

or
O Me O
H
O
R O E H
MeO O
OMe

Claus, R. E.; Schreiber, S. L. Org. Synth., CoIl VoL Ⅶ 1990, 168

A: 1,3-Dipolar cycloaddition of ozone to the olefin. B: Heterolytic cleavage of the initial ozonide. C:
Trapping the dipole with methanol. D: Acetylation. E: Elimination of acetic acid might proceed either
by 1) deprotonation with triethylamine, 2) Baeyer-Villiger-type 1,2-hydride shift, or 3) thermal eliminatior
via a six-membered transition state.

B118
AIBN
n-Bu3Sn X n-Bu3SnH n-Bu3Sn
A
H
X=Cl or I

OEt OEt
I Snn-Bu3
O O
-n-Bu3SnI

OEt OEt OEt

O O O
-t-Bu

C H
C N C N CN
Me
t-Bu
e
M Me

Stork, G.; Sher, P. M. J. Am. Chem. Soc. 1986, 108, 303.

A: Reduction of Bu3SnX with NaBH3CN to form a low concentration of Bu 3SnH to avoid the premature
reduction of the radical intermediates. B: 5-exo-trig Radical cyclization. C: Addition to the isocyanide
followed by elimination of a stable t-butyl radical.
B119

N N
N N
F3B N N N N
N
O

A OBF3 B OBF3

N N
-N2
N O
BF3 BF3
C O D O E

Lang, S.; Kennedy, A. R.; Murphy, J. A.; Payne, A. H. Org. Lett. 2003, 5, 3655.
A: Generation of a stable benzylic carbocation. B: Intramolecular attack of the azide. C: formation
ofan aziridine. D: Restoration of the aromaticity. E: 1,2-Alkyl shift.

B120
Ph N O

Ph Ph O Me
N N N
Cl O H Cl O A B
NEt3 O

Ph N
O O
O Me
N N Ph
C Ph N D O
O
O O

Quadrelli, P., Mella, M.; Invernizzi, A. G.; Caramella, P. Tetrahedron 1999, 55, 10497.
A: Elimination of chloride ion is facilitated by the formation of an oxime anion. B: Addition of NMO to
the nitrile oxide. C: Generation of an acylnitroso compound. D: Hetero-Diels-Alder reaction.

B121
H
O O O H
H -H+
+H+ B
A
 H
O O
-H+
+H+ B
A

Drouin, J.; Leyendecker, F.; Conia, J., M. Tetrahedron. 1980, 36, 1203.
A: Tautomerization. B: Oxy-ene reaction.

B122
Me Me Me Me Me Me

-N2

H A B C
OO N O N O
S N S O SO2
O N
Cl CH2 O
NEt3

Me Me Me Me Me Me Me Me

95oC -SO2

D
O O O O
SO2 SO2 SO2

Fischer, N.; Opitz, G. Org. Synth., Coll. Vol. Ⅴ 1973, 877.

A: Generation of a sulfene. B: 1,3-Dipolar cycloaddition of diazomethane to the sulfene. C:
Extrusion of N2 to form an episulfone. D: Ramberg-Bäcklund reaction.

B123
PPh3Br PPh3
A
H

t-BuO K

O O O
PPh3 PPh3
PPh3
B C D

H
 Ph

+ O Ph
E
O Ph
O
PPh3 Ph

Dauben, W. G.; Ipaktschi, J. J. Am. Chem. Soc. 1973, 95, 5088.

A: Generation of an ylide. B: Michael addition. C: Regeneration of a phosphorus ylide. D:
Intramolecular Wittig reaction (irreversible). E: The unstable diene was trapped as the Diels-Alder
product.

B124
OTBS
Cl SePh
O Me Me
O PhSeCl O
Me
A B
OTBS OTBS

HO OH
PhSe Me PhSe Me PhSe Me
aq H2O2
O O O
Sit-BuMe2
H H H
Cl

OH
H Ph Ph
O Se Me O Se Me Me
-PhSeOH
O H O O
H C
H H H
Curran, D. P.; Rakiewicz, D. M. Tetrahedron 1985, 41, 3943,
A: Claisen-lreland rearrangement. B: Selenolactonization. C: syn-Elimination of the selenoxide.

B125
O Ph O Ph
Ph S
hv
Ph S H Ph Ph S Ph S
Cl
O
B
 O Ph HO Ph Ph
H S
A Ph S B Ph S S C
Ph
Vedejs, E.; Eberlein, T. H.; Ma zur, D. J.; McClure, C. K.; Perry, D. A.; Ruggeri, R.; Schwartz, E.;
Stults, J. S.; Varie, D. L.; Wilde, R. G.; Wittenberger, S. J. Org. Chem. 1986, 51, 1556.
Norrish type II reaction. A: n-π* Transition. B: Intramolecular abstraction of a hydrogen atom
followed by fragmentation to form a highly reactive thioaldehyde. C: Hetero-Diels-Alder reaction.

B126
Me O Me O
Me -N2
Me
RuLn
N N A
AcO RuLn AcO
N N
Me Me Me
-RuLn
O AcO
O B C
AcO AcO Me
Ru Me O
Me
Ln
Kennedy, M.; McKerve y, M. A. J. Chem. Soc., Perkin Trans. Ⅰ1991, 2565.
A: Formation of a rhodium carbene complex. B: C yclopropanation of the aromatic ring. C: 6e
Disrotatory electrocyclic reaction.

B127
Ph
Ph
Cr(CO)5 (CO)4Cr (CO)4Cr
-CO
OMe
OMePh A OMe Ph

Ph
(CO)4Cr OMe OMe
Ph Ph
OMe Ph B C
Cr Ph Cr Ph
(OC)3 C (OC)3
O
O

OMe OMe OMe

Ph Ph Ph
Cr(CO)3 D Cr(CO)3 Cr(CO)3
C Ph Ph Ph
O H
O OH
 Dötz, K. H. Angew. Chem. Int. Ed. Engl. 1975, 14, 644.
Dötz reaction. A: Alkyne metathesis of Fischer carbene complex. B: Insertion of CO. C: Reductive
elimination to form a ketene. D: 6e Electrocyclic reaction.

B128
Et MgBr
Et Et Ti(Oi-Pr)2
i-PrO -EtH
Ti Oi-Pr)2
i-PrO ( H Ti(Oi-Pr)2 H Ti(Oi-Pr)2
A B C
Ti(Oi-Pr)2
Et MgBr

OMe
MeO
Me O O Me O OMe
Me Ti(Oi-Pr)2 Ti(Oi-Pr)2
Ti(Oi-Pr)2 D

MeO
Ti(Oi-Pr)2
Me O Me O Me OMgBr workup Me OH
OMe 2EtMgBr
Ti(Oi-Pr)2 E F +H+
+
Et
Ti(Oi-Pr)2
Et

Kulinkovich, O. G.; Sviridov, S. V.; Vasilevski, D. A. Synthesis 1991, 234.

Kulinkovich reaction. A: Substitution of the isopropoxide with EtMgBr. B: β-Elimination. C:
Reductive elimination to form a titanium ethylene complex (or a titanocyclopropane). D:
Carbotitanation. E.: Formation of a cyclopropane. F: Regeneration of the active reagent.
解答 上级编
C001
H OMe
O OMe MeO O O
OMs Me MeO Me
A H
Me H H OMs
t-Bu t-Bu

t-Bu

MeO OMe MeO OMe

OH OH
B Me H Me H
t-Bu t-Bu

Yamauchi, T.; Hattori, K.; Nakao, K.; Tamaki, K. Bull. Chem. Soc. Jpn. 1987, 60, 4015.
A: Formation of an epoxide by intramolecular SN2 reaction of a hemiacetal. B: E1-like cleavage of the
reactive epoxide.

C002
NO2 NO2

O
NEt3
O2N O2N Cl
O2S H O2S
N N OMe
H
H
NO2 NO2 NO2

O O
O2N O N O N O
O2S O O2S A OO S
N Ar N Ar N Ar
O
H H
NEt3
O2N
-SO2 O2N NC
O +
O2N OH OMe
N Ar
O2N
S
O O

Huber, V. J.; Bartsch, R. A. Tetrahedron 1998, 54, 9281.

Smiles rearrangement. A: Addition-elimination process via a Meisenheimer complex.
C003
H Me
Me
Me Me Et
Me Et Me
O O TiCl
4
TiCl4

H Me H Me
Me
Me
H H Et workup H Et
H
Cl4TiO Me Me Me O Me Me O
TiCl4
Et H

Bender, J. A.; Arif, A. M.; West, E G. J. Am. Chem. Soc. 1999, 121, 7443.
Cation-olefin cyclization initiated by Nazarov reaction ( ref B026).

C004
BrMg O BrMg
O O

Cl A Cl B

OH OMgBr OMgBr O
workup

C +H+
H
Kato, T.; Kondo, H. ; Nishino, M.; Tanaka, M.; Hata, G.; Miyake, A.
Bull. Chem. Soc. Jpn. 1980, 53, 2958.
A: Addition of CH2=CHMgBr to the ketone from the opposite side of the α-substituent. B: 1,2-Alkenyl
shift. C: Anion-accelerated oxy-Cope rearrangement via a chair-like transition state.

C005
TfO
Ph Ph Ph Ph Ph Ph
EtO Si EtO Si EtO Si
OTf
H A H
O O O

Me OH Ph Ph
EtO Si EtO2C
prydine OTf -H+ 120oC
O Me
SiPh2
Me OH O
 EtO2C H
EtO2C Ph EtO2C Ph F
H Ph Ph
Me H Me Si TBAF Me Si
H SiPh2
H O O
O B H2O2
H C

CO2Et CO2Et O
+H+ OOH OH
Me SiPh2 Me SiPh2
F OH OH

CO2Et F CO2Et
Me O SiPh2F +H+ Me OH

OH OH

Sieburth, S. M.; Lang, J. J. Org. Chem. 1999, 64, 1780.

A: Protodesilylation to form a silyl triflate. B: Intramolecular Diels-Alder reaction. C: Tamao-Fleming
oxidation.

C006

NHTs NHTs TsN H H

TsNHNH2 NaH
O O O

O N N H H
NHTs N
Ts

NTs NTs O
-ArSO2
O O
A B N
N N H Ts
N Ts N Ts O
N N S
R O

O O O
-N2
H
N N N
N N H Ts N N H Ts H Ts
 O OH

N N
H Ts H Ts

Kim, S. H.; Fuchs, P. L. Tetrahedron Lett. 1996, 37, 2545.

A: Cleavage of the epoxide helped by the hydra zone anion. B: Conjugate addition of the sulfonamide
anion.

C007
O Me
Me O OH Me Me O
-H2O N Ph
H -H+ O
Me N Ph
+H+ H O
Ph NH2
H
Me Ph O

O t-Bu
O N
H
O Ph N Me
t-Bu N C Ph O
Me A Ph
O O
Me N Ph
H
Me
Me
H
N t-Bu O
-H+ O O
O O H
Me N
+H+ Ph N Ph N t-Bu
B O
Ph Me Ph Me
Semple, J. E.; Wang, P. C.; Lysenko, Z.; Joullie, M. M.
J. Am. Chem. Soc. 1980, 102, 7505.
Ugi reaction (four-component condensation, 4CC). A: Most likely, addition of the isocyanide to the
iminium ion and addition of the benzoate ion to the ensuing nitrilium ion takes place simultaneously. B:
Intramolecular acyl transfer reaction (the benzoyl group is activated).
C008
OBn
OMe
OMe OBn OMe OBn OMe
OMe OMe
OMe OMe
HO
O
A B
OMe OH OH
O Me Me
O O O O

Me

H Me
BnO O BnO OMe BnO OMe
OMe
H
OMe OMe OMe
-2H+
H +H+
O O OH
Me Me C Me
O O O O O O

Takemura, I.; Imura, K.; Matsumoto, T.; Suzuki, K. Org. Lett. 2004, 6, 2503.
A: 4e Electrocyclic reaction. B: 6e Electrocyclic reaction. C: Aromatization.

C009
OH F3C F3C
H O N
N
O O
O F Ph A O Ph B
O O O

O
O O HO2C CF3 Ph
CF3 -H+ CF3 +H+ NH
H N Me N
+H+ C
O Ph O Ph O Me
O O

OH
Burger, K.; Gaa, K.; Geith, K.; Schierlinger, C.
Synthesis 1989, 850.
A: ipso-Substitution of the electron-deficient oxazole. B: Claisen rearrangement. C: H ydrolysis of the
azlactone.
C010
I Ph Ph
I Pd(0) Pd
Ph Pd
A I B
Ph

Ph I
H H Pd
Ph Ph Ph
Pd C D
H
H I Pd
I

LnPd
-HI
Ph Ph
E

Larock, R. C.; Tian, Q. J. Org. Chem. 2001, 66, 7372.

A: Oxidative addition followed by carbopalladation to an alkyne. B: Oxidative addition to the aromatic
C-H bond. C: Reductive elimination. D: Oxidative addition to another aromatic C-H bond. E:
Reductive elimination to form the C-C bond.

C011
MeO2C
MeO2C

A B
CO2Me H

H MeO2C
MeO2C
C C

Grissom, J. W.; Calkins, T. L.; Egan, M. J. Am. Chem. Soc. 1993, 115, 11744.
Masamune-Bergman cyclization. A: Radical cyclization of an endiyne. B: Kinetically favored 5-exo-
trig radical cyclization. C: Abstraction of a hydrogen atom from 1,4-cyclohexadiene.
C012
Me
-AcOH O
N N
N N O
H O O A H B
Et O
Me O Me
O Et
HO

O O
Et Et
N N
O
N Et
N N N
H H H
OAc
OAc

Harley-Mason, J.; Atta-ur-Rahman Tetrahedron 1980, 36, 1057.

A: Formation of a mixed anhydride. B: Acylation of the tertiary amine followed by cleavage of the C-N
bond assisted by the nitrogen lone pair of the indole.

C013
OH t-BuOOH OH OH
VO(acac)2
O OMEM O R O R
Me Me A OH B OH

O OH HO O
-H+ -H+ O
OH O Me
+H+ Me
R OMEM MEMO
C
O O Me Me H H

HO
H OHC O
O -H+ H
MEMO H O +H+ MEMO
D OH
Me
H Me H MeMe

Richter, E; Maichle-Mossmer, C.; Maier, M E. Synlett. 2002, 1097.

Achmatowicz reaction (A-C). A: Epoxidation directed by the h ydroxy group. B: Cleavage of
theepoxide followed by the ring opening to form a cis-enal. C: C yclization to form a lactol. D:
Intramolecular Diels-Alder reaction.
C014
n-Bu n-Bu n-Bu
-HCl hv
A
O O O
H N N
O
Cl O
N
O

n-Bu n-Bu n-Bu n-Bu

-H+
B C H +H+
O OH OH OH
H N D N
N O O HO

n-Bu n-Bu n-Bu

TsCl workup

pyridine OH E N OH NH OH
N
TsO O
OH2
Corey, E. J.; Arnett, J. E; Widiger, G. N. J. Am. Chem. Soc. 1975, 97, 430.
Barton reaction (A-D, ref 097). A: Photo-induced homolytic cleavage of the nitrite. B: Abstraction of
a hydrogen atom via a six-membered transition state. C: Recombination of .NO with the resulting
radical. D: Tautomerization to form an oxime. E: Beckmann rearrangement ( ref A055).

C015
O O O O -N2 O O
N N
N N
Me A Me Me
RhLn RhLn RhLn

Me Me Me O
O
O B O
RhLn
O O O
RhLn

Me O Me O Me O
H SmI2 H H

C O O D O
O O O
H H H
H I2Sm H SmI2 H
 SmI2 SmI2
O H O O H O HO H O
workup
E F +H+
O O O
H H H
SmI2 SmI2

Padwa, A.; Sandanayaka, V. P.; Curtis, E. A.

J. Am. Chem. Soc. 1994, 116, 2667.
A: Formation of a rhodium carbene complex. B: Formation of a carbonyl ylide. C: 1,3-Dipolar
cycloaddition. D: SET to form a ketyl radical. E: Homolytic cleavage of the C-O bond. F: SET.

C016
Me3Si N2 N
Me3Si N
Me3Si N2 O
N2 O C
Me Me Me
H Me Me Me
O O A O O O O
n-Bu

N
N
C
Me Me Me H Me
Me -N2 Me H
O O O O
O Me O Me
O B O

H Me Me Me
silica gel H -H +
O Me Me Me
+H+ OH HO O HO O

Walker, L. F.; Connolly, S.; Wills, M.

Tetrahedron Lett., 1998, 39, 5273.
A: Peterson olefination ( ref A074) followed by elimination of N 2 to form an alkylidene carbene. B:
C-H insertion.
C017

Cl3C C N

O OH O
DBU
N H MgBr N Cl3CCN N
workup -H +
N N N
Tr Tr A Tr

CCl3 CCl3 CCl3

O N O NH O NH
H OR Ca(OCl)2
N N N H2O

N N N
Tr Tr Tr

CCl3 CCl3 CCl3

H2O
O NH O N O NH

N N aq HCl N -H+
Cl +H+ Cl +H+
N B N N
Tr Tr Tr

HO CCl3 O

O NH2 O CCl3 OH

N -H+ N NH2 N NH2

Cl Cl Cl
N N N
Tr Tr Tr
Commercon, A.; Ponsinet, G. Tetrahedron Lett. 1990, 31, 3871.
A: Formation of a trichloroacetimidate followed by aza-Claisen rearrangement. B: While formation of
five-membered rings is kinetically favored, acti vation by the imidazole ring directed the cycli zation to
form a six-membered ring.

C018

H Et
MeO O MeO O
benzene
Me
R reflux
OMe OH Me OMe OH
 MeO O MeO O MeO OH
H

R R A R
OMe OH OMe OMe

MeO OMe

MeO OMe
OH MeO
R
MeO O
OH
B
Me
R OMe Me
OMe Me
Me
Tatsuta, K.; Tamura, T.; Mase, T. Tetrahedron Lett. 1999, 40, 1925.
A: Restoration of the aromaticity. B: Hetero-Diels-Alder reaction.

C019
H2N Ts
F3B H Ts
O -H+ F3B O NH NTs
Ph H +H+ Ph H Ph

PPh3 NTs Ts
N Ph
Ph
C
Ph3P OMe CO2Me
OMe A O
O PPh3

Ts Ts Ts
N Ph -H+ N Ph N Ph
+H +
B
Ph3P HCO2Me C Ph3P H CO Me
2 CO2Me

Xu, Z.; Lu, X. J. Org. Chem. 1998, 63, 5031.

A: Conjugate addition of Ph 3P to the allenyl ester to form an enolate. B: 5-endo-trig Cyclization to form
an ylide. C: Proton transfer followed by elimination of Ph 3P.
C020
Me Me
i-PrO +2i-PrMgCl
Ti(Oi-Pr)2 H Ti(Oi-Pr)2 H Ti(Oi-Pr)2
i-PrO -2Oi-Pr- Me Me
Me Me
Me
- Me Me
Me Me
A Ti(Oi-Pr)2 Ti(Oi-Pr)2

Me OEt
OEt
CO2Et
Ti(Oi-Pr)2 O O
Ti(Oi-Pr)2 TBSO Ti(Oi-Pr)2
TBSO B TBSO C

OEt O
O
TBSO Ti(Oi-Pr)2 TBSO
Ti(OR)3 D

OTi(OR)3 OH O FeCl2
workup FeCl3
TBSO TBSO TBSO
+H+
O O

NaOAc
E TBSO Cl FeCl2 TBSO Cl MeOH

O O O
H OAc

TBSO Cl TBSO Cl TBSO

Hanazawa, T.; Okamoto, S.; Sato, F. Tetrahedron Lett. 2001, 42, 5455.
A: Formation of a titanium-propylene complex or a titanacyclopropane derivative ( ref B128). B:
Olefin exchange. C: Intramolecular insertion of the carbonyl group to the titanium complex. D:
Formation of a cyclopropane. E: Oxidative cleavage of the cyclopropane ring.

C021
B Ph
H
Cl Cl
Cl O Cl O A Cl
H O
 Ph Ph Ph
O
O O
B Cl C D

n-Bu

Ph workup Ph
O OH

Danheiser, R. L.; Martinez-Davila, C.; Morin, J. M., Jr. J. Org. Chem. 1980, 45, 1340.
A: α-Elimination to form a carbene. B: Cyclopropanation. C: β-Elimination to form a cyclopropanol
anion. D: Anion-accelerated vinylcyclopropane rearrangement (homolytic cleavage followed by
recombination of the diradical).

C022

O
O N N
H N3 P(OPh)2

-H2O
A

N O N P(OPh)2
P(OPh)2 N
N N
N B N C
N

O
N O N P(OPh)2
N P(OPh)2 -N2 KOH
N CO2H
N N D

Hamada, Y.; Shioiri, T. Org. Synth., Coll. Vol. Ⅶ 1990, 207

A: Formation of an enamine. B: 1,3-Dipolar cycloaddition. C: Cleavage of the N-N bond. D:
Tiffeneau-Demjanov-type ring contraction.
C023
TMS TMS TMS
I
Li
CH3
O O workup HO
O O O O O O O O O
+H +
A
Me N Me N Me N

O O
TMS TMS
Me O Me
Me O
H
Ac2O O O
O O O O O O
B
Me N Me N

TMS O TMS

O Me
O O O TMS
O
O O H O O O
C
Me N Me N Me N

AcO
O TMS O H SiMe O
3
-CO2 H OAc
D N E N N
Me Me Me

Nayyar, N. K.; Hutchison, D. R.; Martinelli, M. J. J. Org. Chem. 1997, 62, 982.
A: Demethylation via an SN2 process. B: Cycli zation of the mixed anhydride followed by formation of a
1,3-dipole. C: Intramolecular 1,3-dipolar cycloaddition. D: Decarboxylation. E: Protodesilylation.

C024
Me Me Me
-H+
O OH A O OH B O
O
PhSe Br PhSe
PhSe
 NaIO4 Me toluene Me Me

O reflux O D
O O O
C O
H
Se
Ph O

Petrzilka, M. Heir. Chim. Acta 1978, 61, 3075.

A: Selenation of the electron-rich enol ether. B: Intramolecular acetal formation. C: β-Elimination of
the selenoxide. D: Claisen rearrangement.

C025
Cl H2O
Hg HgCl
Cl HO HgCl
AcO AcO AcO
O O -H+ O

BnO OMe A BnO OMe +H+ BnO OMe

OBn OBn OBn
HgCl ClHg
O O O
AcO AcO AcO
-H+ O O +H+

BnO H BnO H B BnO OH

OBn OBn OBn
Chida, N.; Ohtsuka, M.; Nakazawa, K.; Ogawa, S.
J. Chem. Soc., Chem. Commun. 1989, 436.
Ferrier rearrangement. A: Oxymercuration of enol ether. B: Intramolecular aldol reaction of the
mercury enolate with the aldehyde.

C026
O

O H i-Pr
O Me O O
Me O H Me
Ph Me Ph
Ph
H Me Me
Oi-Pr Me
O O

i-Pr OLi O i-Pr OH O i-Pr

Me O workup
Ph H i-Pr Me Me
Ph Ph
A +H+
O Li O Me Me Me Me
 O OH

OH O i-Pr OH OH OH OH
NaOH Me Me workup Me
Ph Ph Ph
MeOH +H+
Me Me Me Me Me Me
Mascarenhas, C. M.; Duffe y, M. O.; Liu, S.-Y.; Morken, J. P. Org. Lett. 1999, 1, 1427.
Tishchenko reaction. A: Intramolecular hydride transfer (Cannizzaro-type reaction) through a
chair-like transition state.

C027

F3B F3B
BF3
H O H O H O
-H+
H
O A O +H+ O
Me Me Me Me Me Me

F3B F3B
H O H O H H O
-H + OH
OH O HO
HO
+H+
Me Me Me Me Me Me
HO HO HO

HO HO HO
-H + O -H2O O O
OH2
+H+ B
Me Me Me Me Me Me
H2O

HO O
-H + OH -H+ Me OH
OH
+H+ O

Me Me
Me
Nagumo, S.; Suemune, H.; Sakai, K. J. Chem. Soc., Chem. Commun. 1990, 1778.
A: Intramolecular acid-catalyzed aldol reaction. B: Grob-type fragmentation.
C028
O O
N N
hv
Me3Sn SnMe3 Me3Sn I

Et C Et
OH O N OH O

O O
N N
N N
A
Et Et
HO O HO O

H H
O O
N N
N N
B I
R I
Et Et
HO O HO O
O
-HI N
N

Et
HO O
Curran, D. P.; Ko, S.-B.; Josien, H. Angew. Chem. Int. Ed. 1995, 34, 2683.
A: Radical addition of an isocyanide to form an imidoyl radical. B: Atom transfer reaction.

C029
Me Me
Me Me
O O
O O O O Me O Me
Ar O Ar O
MeO Cl A N N
Me NMe Me Me H Me Me
B
 Me
AlCl2
O
Me
O
O Me
AlCl2Me NMe
Ar O
N AlCl2 B C
O
Me Me Me MeO
Me

Me
AlCl2 H
O O OH
H
+
-H NaBH4
NMe NMe NMe
workup
O O O
MeO MeO MeO
Me Me Me

OMs OMs
Et3N
NMe NMe
MsCl t-BuOK
O O
MeO MeO Me H
Me

t-BuO

OMs

NMe
NMe
O MeO
MeO Me
Me
O
Fuchs, J. R.; Funk, R. L. Org. Lett., 2001, 3, 3923.
A: Acylation of the imine to form an enamide. B: Retro cycloaddition to form an (α-amidoacrolein. C:
Intramolecular conjugate addition of the electron-rich aromatic ring to the amidoacrolein.

C030
H H
H CH3CHO
H
BH Me
A B B B O
Me H H H
Me Me
H
Me
 Me
H H H
-

Cl B OEt
B B B
H H Cl H
OEt EtO Cl O
OMe Me
Cl Cl Cl Cl
t-BuO H OMe OMe

H H H
NaOAc
aq H2O2
B OOH
H OEt H OEt -MeOH H OH
Cl O Cl B -EtOH Cl B
Me MeO HO
H H H
OOH
OH
O OH
H B H O B H
Cl Cl O
HO OH OH

Brown, H. C.; Mahindroo, V. K.; Dhokte, U. P. J. Org. Chem. 1996, 61, 1906.
A: Sequential hydroboration to form a trialkylborane. B: H ydride transfer via a six-membered
transition state. See Meerwein-Ponndorf-Verley reduction ( ref B002).

C031
Me Me Me Me
Me Me Me Me
N C N HN O
H HN O O O
O Me N O
O O H
O Me N Ph
A Ph S Ph Me S B
Ph
Ph S Ph Me

O
O
O
Ph Ph O S
S Ph S Ph Ph
Ph S Ph
C D E
Ph

Sponholtz III, W. R.; Trujillo, H. A.; Gribble, G. W. Tetrahedron Lett. 2000, 41, 1687.
A: Acti vation of the carboxyl group as an O-acylisourea. B: Generation of a 1,3-dipole. C: 1,3-Dipolar
cycloaddition. D: Decarboxylation to form a 1,3-dipole. E: Intramolecular 1,3-dipolar cycloaddition.
C032
H
O O O
H -H+
Me
A +H+ Me B
Me

Me Me Me
H H Me
O O OH Me

Me
Me H C

Me Me Me
Fukuyama, T.; Li, T.; Peng, G. Tetrahedron Lett. 1994, 35, 2145.
Abnormal Claisen rearrangement. A: Claisen rearrangement followed by tautomerization. B:
Intramolecular oxy-ene reaction to form a cyclopropane. C: Retro oxy-ene reaction.

C033

O O A O B
H S
n-Bu Ph
PhS Cl

O n-BuLi O O
S RCHO S S
Ph Ph Ph
C
H H
R O
R O

O
aq NH4Cl
S
Ph
D
O
R OH S R OH
Ph

O OH
S
E Ph R

Schreiber, S. L.; Satake, K. J. Am. Chem. Soc. 1984, 106, 4186.

A: Formation of a sulfenate. B: [2,3] Sigmatropic rearrangement. C: Deprotonation followed by
addition to the aldehyde (pKa D MSO = 35). D: [2,3] Sigmatropic rearrangement of the sulfoxide. E:
[2,3] sigmatropic rearrangement of the sulfenate.
C034
OTBS OTBS OTBS

RuLn
RuLn RuLn
A
R R
Me Me Me

OTBS OTBS OTBS

B
RuLn RuLn Ru
Ln

Me Me Me

OTBS Me OTBS Me OTBS

LnRu
RuLn LnRu

Me

OTBS Me OTBS
-
RuLn

Me Ru
Ln
Zuercher, W. J.; Scholl, M.; Grubbs, R. H. J. Org. Chem. 1998, 63, 4291.
Domino intramolecular enyne metathesis. A: Alkene metathesis at the terminal olefin. B: Sequential
intramolecular alkyne metathesis to form a kinetically favored, six-membered intermediates. C:
Intramolecular alkene metathesis.

C035
OBoc OBoc OBoc

OBoc O Ot-Bu A O

O H Ph Ph O Ph O

O Ot-Bu
 OBoc OBoc

B O C O

Ph OEt Ph OEt
Jones, R. M.; Selenski, C.; Pettus, T. R. R. J. Org. Chem. 2002, 67, 6911
A: Intramolecular acyl transfer (pKa PhOH = 10, t-BuOH = 19). B: Generation of o-quinonemethide
C: Hetero-Diels-Alder reaction to form an endo-adduct.

C036
O

OBn N Br OBn Br

BnO O BnO O
O
BnO O BnO O
OBn OBn A

OBn Br OBn OBn

BnO O BnO O HO Me -H+ BnO O
BnO O BnO BnO OMe
OBn OBn OBn

Fraser-Reid, B.; Konradsson, P.; Mootoo, D. R.; Udodong, U.

J. Chem. Soc., Chem. Commun. 1988, 823.
A: Bromination of the olefin causes the formation of a five-membered oxonium ion.

C037
Me Me
Me Me S SMe
Cl Me S
Me Me C Me Me
Me A Me B C Me C
Me
C Me
Me Me

Me Me
S Me S OH2 HS OH Me
HgCl2 Me -H+
Me Cl Me
C Hg Me
Me Me +H+
Me Cl ClHg Me Me Me HgCl
Me

H
O Me OH H O Me
-H+
Me C Me Me
Me Me HgCl Me Me Me Me
Me
Cl
 Michelot, D.; Linstrumelle, G.; Julia, S. J. Chem. Soc., Chem. Commun. 1974, 3, 10.
A: Generation of an alkylidene carbene. B: Formation of a sulfur ylide (carbene is electrophilic). C:
[2,3] Sigmatropic rearrangement.

C038

O H OMe
O
H OMe
H CO2Me
OMe
N3 A OMe N3
O N3
O
OH
CO2Me -H2O CO2Me CO2Me
N3
H N3 N
N
N
MeO
CO2Me

-N2 N CO2Me
B C NH2
H N CO2Me
H

or
CO2Me

N CO2Me
C N
N CO2Me
H

N CO2Me
H
Knittel, D. Synthesis 1985, 186.
A: Claisen-Schmidt reaction. B: Formation of an azirine. C: Cleavage of the azirine ring to form
either 1) a nitrene which undergoes C-H insertion or 2) a diradical that recombines to form, upon
aromatization.an indole.
C039
OLi

Me OLi OLi workup OH OH H SO

O 2 4

Me +H+ Me MeOH
Me Me Me

MeOH
OMe
OH2 OH -H+ OH2 -H+ H
C Me
Me Me +H+ Me
Me Me
H

OMe H OMe OMe O

-H+ H3O+
H
A
Me Me
Me Me Me Me Me Me

Hiyama, T.; Shinoda, M.; Nozaki, H. J. Am. Chem. Soc. 1979, 101, 1599.
A: Nazarov reaction ( ref B026).

C040
OCOCF3
Ph
I
Ph OCOCF3 I
OH O OCOCF3 O
HO Me
OMe OMe OMe
A

Me Me Me

O
OMe O
-H+ Me
O Me O OMe
Me
B O
Me
Me
Me

Me
O O Me
mesitylene
Me OMe Me OMe H
200oC C
O O O
Me Me OMe
O
Hsiu, P.-Y.; Liao, C.-C. J. Chem. Soc., Chem. Commun. 1997, 1085.
A: Oxidation of the phenol to form a mixed o-quinone monoacetal. B: Intramolecular Diels-Alder
reaction. C: Cope rearrangement.

C041
MeO MeO MeO

N O N O N O
MeO MeO MeO
A H OMe
H

MeO MeO

N O N O
MeO MeO
H B H H
H
H H

Naito, T.; Tada, Y.; Nishiguchi, Y.; Ninomiya, I.

Heterocycles 1981, 16, 1137.
A: 6e Electrocyclic reaction. B: Reduction of the acyliminium ion from the convex face.

C042
O O O
H
B R
TBS A O
R R TMS
t-BuMe2Si
O TMS
O

R R
B O TMS
C
TBSO TMS TBSO

TBSO O workup TBSO O

D +H+

TMS R TMS R

Takeda, K.; Takeda, M.; Nakajima, A.; Yoshii, E.

J. Am. Chem. Soc. 1995, 117, 6400.
A: 1,2-Addition of the enolate to the acylsilane. B: Brook rearrangement. C: Cyclopropanation. D:
Anion-accelerated divinylcyctopropane rearrangement.
C043
SmI2
Me Me Me O
H H
O O A O O
SmI2
SmI2 H
O

I2SmO I2SmO I2SmO

Me Me Me SmI2
H
B C
H H H H
O O O

I2SmO HO
Me workup Me
H H
D +H+
H H
O O

Boffey, R. J.; Santagostino, M.; Whittingham, W. G.; Kilburn, J. D.

Chem. Commun. 1998, 1875.
A: SET. B: 5-exo-trig Radical cyclization to form a radical at a cyclopropylcarbinyl position which
induces cleavage of the cyclopropane ring (cf. radical clock). C: 5-exo-dig Radical cyclization. D:
SET.

C044
O
OMe H2N
NH2
Me O Me Me O +H+
H A
OTs +H+
H H H
MeO
Me Me

NH2 H
O O O O
Me NH -H+ Me Me
O NH2 O
+H+
Me NH2 Me
HO O B O O Me
H Me H H
 H2O O
Me
O O O O
Me C H
Me O Me O Me O
-H+

C O D O +H+ O

H H H
Me O
-CO2 Me OH +
-H
H O
O +H +
H H
H MeO

Tietze, L. F.; WöIfling, J.; Schneider, G. Chem. Ber. 1991, 124, 591.
A: Grob-type fragmentation. B: Knoevenagel reaction ( ref A018). C: Intramolecular hetero-Diels-
Alder reaction. D: Retro Diels-Alder reaction to generate a highly reactive acylketene.

C045
Me O
O OH
O
Me Me
OEt OEt
Me
Br Br Br A
CO2Et
t-Bu t-Bu

O Me O O
O
C
B Me C
Me Me

CO2Et
O OEt

Me O O Me O O Me O
O
Me
Me Me
O O O
H
EtO

Me Me
-CO2 Me workup Me
+H+
O OH
 Shindo, M.; Sato, Y.; Shishido, K. J. Org. Chem. 2001, 66, 7818.
A: Formation of an ynolate. B: Addition of the ynolate to the ketone leads to the formation of a strained
β-lactone enolate. C: Claisen condensation followed by aromatization with decarboxylation.

C046

Me OMe CO2Me CO2Me

O -N2
Me O
N N O
- O OMe
Me Me
A

O
MeO O MeO2C
MeO
H H H
OMe
B OMe C OMe
O O O

Spino, C.; Rezaei, H.; Dupont-Gaudet, K.; Belanger, F.

J. Am. Chem. Soc. 2004, 126, 9926.
A: Fragmentation to form a dialkoxycarbene. B: Cyclopropanation. C: Cleavage of the cyclopropane
ring.

C047

MeO Me
O
MeO MeO
O N Ph
N Ph N
Me
H
Br Ph O
H
Me Me
LiAlH4 MeO MeO
AlCl3 mCPBA O
N N A
Ph Ph
 H
MeO C Me MeO Me MeO Me
-H+
O O O
N B N +H+ N
H
Ph Ph Ph

MeO MeO
-H+ Me KCN Me
+H + N OH N OH

Ph Ph

MeO CN MeO
CN

N Me N Me

Ph Ph
Makisumi, Y.; Takada, S. Chem. Pharm. Bull. 1976, 24, 770.
A: [2,3] Sigmatropic rearrangement of the N-oxide. B: [3,3] Sigmatropic rearrangement.

C048
O S N CO2Me CO2Me CO2Me
N PhMgBr N
A S S B
O O
Ph

Ph Ph
CO2Me workup HMPT
S NHCO2Me S NHCO2Me
S O O O
EtOH
Ph 80oC

H H
NHCO2Me N NH
O
C D OMe O
O SPh O O
H
P(NMe2)3

Anderson, G. T.; Chase, C. E.; Koh, Y-H.; Seien, D.; Weinreb, S. M. J. Org. Chem. 1998, 63, 7594.
A: Hetero-Diels-Alder reaction. B: Cleavage of the S-N bond by SN2 attack of Ph MgBr. C: [2,3]
Sigmatropic rearrangement (reversible process). D: Irreversible cleavage of the S-O bond by attack of
a thiophile (P(NMe2)3) generates an alkoxide ion which then cyclizes to give an oxazolidinone.
C049
Me Me Me Me
H B t-Bu Si Cl
Me O3
O O A OTBS

Me Me Me Me Me Me
O
Me O Me Me
O O
O
O O
OTBS B O C
OTBS
Me Me Me Me Me Me

Me Me H2 Me Me
H H
Pd/C OH OH
O + O +
O O D
H H Me Me
Me Me Me Me Me OH Me OH
Casey, M.; Culshaw, A. J. Synlett
A: Formation of a silyl enol ether. B: 1,3-Dipolar cycloaddition of O3 followed by cleavage of the
ozonide to form a 1,3-dipole (carbonyl oxide). C: 1,3-Dipolar cycloaddition. D: Reductive cleavage of
the O-O bond.

C050
Ar
PPh3
O Ar
Ar PPh3
CN O
O H
O O CN
Et A B
N C N N NHEt N NHEt
R
H R R O

O
O O
Ar Ar Ar
O3 Ph3
PPh3 PPh3 P O
O O C O
CN CN NC O O
 Br
OMe Br
OMe
Br Br OMe

Ar
O
D O H2N
O N
H
CN O
Wasserman, H. H.; Wang, J. J. Org. Chem. 1998, 63, 5581.
A: Acti vation of the carboxylic acid as an O-acylisourea. B: Acylation of the stabilized ylide. C: 1,3-
Dipolar cycloaddition of O3 to the ylide. D: Fragmentation to generate an acyl cyanide.

C051
O O O
Me Cl Me
-H+ O
OH
O O O
NH2 +H+ NH O NH O O
CO2Et CO2Et CO2Et
Pr Pr Pr

NaBH4
-AcOH O N O H2SO4 O N OH +H+ O N OH2
CO2Et CO2Et CO2Et
A Pr EtOH Pr Pr
B
HOEt
TMSCH2MgCl
O N O N OEt O N OEt
-H+ CeCl3
CO2Et
Pr Pr C Pr

O OEt O OEt

Cl2Ce CH2SiMe3

O OEt O OEt O OEt

N N N
SiMe3
SiMe3
Pr Pr Pr
O
SiMe3 SiMe3
O

Cl2Ce CH2SiMe3
 H
aq HCl H
O OEt O O
N N N
+H +
SiMe3 SiMe3 D
C Pr Pr Pr
Chalard, E; Remuson, R.; Gelas-Mialhe Y.; Gramain J.-C.; Canet I.
Tetrahedron Lett. 1999, 40, 1661.
A: Formation of a succinimide via a mixed anhydride. B: Partial reduction of the imide. C: Peterson
olefination ( ref A074) to form an allylsilane. D: Intramolecular addition of the allylsilane to the
acyliminium ion.

C052
Et3N O
H O
CO2H (COCl)2 C
Cl
Et3N A

Cu(OAc)2
O MeLi Me Mn(OAc)3 Me
OH O
B Mn(OAc)2

Me Cu(OAc)2
O
H
C D E
CuOAc

Me Me
O O

Me Me
O O
Snider, B. B.; Vo, N. H.; Foxman, B. M. J. Org. Chem. 1993, 58, 7228.
A: Formation of a ketene. B: Intramolecular [2+2] cycloaddition. C: Generation of an oxygen radical.
D: Cleavage of the cyclobutane ring to form a stable tertiary carbon radical. E: 5-e xo-trig Radical
cyclization followed by oxidation with Cu(OAc)2.
C053
Me3Si
O H
Me3Si OTf O SiMe3
Ph H
O -H+ O Ph

Ph H OH +H+ Ph
Ph SiMe3
SiMe3

Ph

Ph O Ph O
Si Me
H Me Me
Ph

Roush, W. R.; Dilley, G. J. Synlett. 2001, 955

Intramolecular Hosomi-Sakurai-type reaction.

C054

O O O
n-Bu
O H
Br Br Li
O A O Br Br
Br
Br Br O n-Bu O

O
i-Pr3SiCl
O i-Pr3SiO

O O OSii-Pr3

H
hv O
C
O N2 O O
B C
O O i-Pr3SiO
i-Pr3SiO

O
OSii-Pr3 OH OSii-Pr3
O O
C -H+
i-Pr3SiO
D O +H+ O
OSii-Pr3 OSii-Pr3
OSiPr3 E

Danheiser, R. L.; Trova, M. P. Synlett. 1995, 573.

A: Formation of an alkylidene carbene via α-elimination followed by insertion of the carbene into the C-
C bond (Kowalski reaction). B: Wolff rearrangement. C: [2+2] Ketene cycloaddition. D: 4e
Electrocyclic reaction. E: 6e Electrocyclic reaction followed by aromatization.

C055

n-Bu H
OTf Ts
N N N Me
Ts Ts Me I
Ph
A

Ph Ph Ph

Ph Ph
Ts Ts Ts Me Ts Me
N Me N Me N N

B C

Ph Ph

Feldman, K. S.; Mareska, D. A. J. Org. Chem. 1999, 64, 5650.

A: Addition of a sulfonamide ion to the electron-deficient acetylene to form an alkylidene carbene. B:
Cyclopropanation. C: Homolytic cleavage of the strained cyclopropylidene ring.

C056
OBn OBn OBn
H NH3 H HO H H
O HO

HN N
OHC H
OH OH

OBn OBn OBn

H H NH4OAc H
-H2O AcOH
N N 75oC N
H H
OH
 OBn OBn OBn

H
H H -H+ H

A B
HN HN HN

Heathcock, C. H.; Stafford, J. A. J. Org. Chem. 1992, 57, 2566.

A: Aza-Diels-Alder reaction. B: Cation-olefin cyclization.

C057
H2
Lindlar catalyst
A
HO OH
HO OH

H
H OH
B H H C

HO OH HO

Nicolaou, K. C.; Petasis, N. A.; Zipkin, R. E.; Uenishi, J.

J. Am. Chem. Soc. 1982, 104, 5555.
A: Partial reduction of the alkynes to form a tetraene. B: 8e Conrotatory electrocyclic reaction. C: 6e
Disrotatory electrocyclic reaction.

C058
O Cl
A
O
Zn Cl
O Cl Cl
O Tol O Tol
Cl S S
Cl O O
Cl A R
Cl Me
N(Boc)2 N(Boc)2

Cl
Cl Cl O O Cl
H H O
Cl O Cl O Me
o o
S T l B S T l C O
R O R O STol
N(Boc)2
 Marino, J. P.; Rubio, M. B.; Cao, G.; de Dios, A.
J. Am. Chem. Soc. 2002, 124, 13398.
A: Generation of dichloroketene. B: [3,3] Sigmatropic rearrangement. C: Cyclization of the
carboxylate to the sulfenium ion.

C059
O
Me Me
Cl3Al Cl O
MeO S MeO
Me Me S
Cl
CN A B
N N R'
R

Cl

Me Me
Cl3Al Cl S Me
HS O S O
MeO MeO MeO
O Me Me
C CN
N R' N R' N
R R

Cl

Chung, J. Y. L.; Reamer, R. A.; Reider, P. J. Tetrahedron Lett. 1992, 33, 4717.
A: FriedeI-Crafts acylation at the indole 3-position. B: Cleavage of the strained four-membered ring by
chloride ion. C: Intramolecular electrophilic substitution by the resulting sulfenyl chloride.

C060
O O

Me O Me OMe
Me H
A O
C
PdLn
PdLn

Me O
O O
Me -H+ O OMe
Me OMe
OH +H+ Me C
C
B PdLn
PdLn HO
 Me O Me O
-Pd(0)Ln
OMe OMe
O PdLn O
Me
Me Me
H
Minami, I.; Yuhara, M.; Tsuji, J. Tetrahedron Lett. 1987, 28, 629.
A: Formation of an allenylpalladium species. B: Addition of the acetoacetate anion to generate a
π-allylpalladium complex. C: Intramolecular nucleophilic attack to the π-allylpalladium complex.

C061
Me Me
Me Br
LnPd Me
Pd(0)Ln Br Br PdLn
LnPd
A B
Br
O O O O

BrMe Me H
PdLn
Me
LnPd H -
PdLn Br
Br C
O O O
Me yer, R E.; Parsons, P. J.; de Meijere, A. J. Org. Chem. 1991, 56, 6487.
A: Oxidative addition. B: Sequential intramolecular carbopalladation. C: β-Elimination.

C062
H
O O
O OH O OH2
+H+ -H+
O
H HO SiMe3 +H+
Me3Si

O O SiMe3
H decalin H
O O O
170oC
Me3Si A Me3Si O
 Me3Si Me3Si Me3Si
O EtAlCl2 O O

O O O
Cl2EtAl
AlEtCl2

Me3
Si
Cl - e
O M 3SiCl O workup O
B +H+
H OAlEtCl H OAlEtCl H OH
Paquette, L. A.; Ladouceur, G. J. Org. Chem. 1989, 54, 4278.
A: Claisen rearrangement via a boat-like transition state. B: Intramolecular Hosomi-Sakurai reaction.

C063
H H
O O OMe O OMe
O O
OH OH
N Br Ph O A Ph O
H Me Me
Br
O
O N O N
O O

Br Br
H H H
O OMe O OMe O OMe
O O O
OH OH OH
Ph O Ph O Ph O
Br Me B Me C Me

ZnX2
BrZn ZnX
H
O OMe O O
Zn OH OH OH
BzO BzO BzO
Me Me Me

OZnX OH
-H+ O workup O
BzO BzO
D Me +H + Me

Holt, D. J.; Barker, W. D.; Jenkins, P. R. J. Org. Chem. 2000, 65, 482.
A: Radical bromination of the benzylic position. B: Formation of a stable carbocation. C: SN2
reaction. D: 1,2-Alkyl shift.
C064

A B
N NTs N N Ts N N
H N N
n-Bu

C D
H
Bian, N.; Jones, M., Jr. Tetrahedron Lett., 1993, 25, 3967.
A: Formation of a diazoalkane via α-elimination. B: Elimination of N2 to form a carbene. C: Insertion
of the carbene to the C-C bond. D: Retro Diels-Alder reaction.

C065
Ns N NH2
NH2 SiMe3 SiMe3
Ns N
TBSO TBSO
H -H+
CO2Et
A OH +H+ O
N N PPh3
EtO2C PPh3 Ph3P CO2Et
N NH
EtO2C

SiMe3 SiMe3
TBSO TBSO
B O H
N N H
HN S N
H O
O2N

SiMe3
-N2
TBSO C H
C
H
Myers, A. G.; Zheng, B. J. Am. Chem. Soc. 1996, 118, 4492.
A: Mitsunobu reaction ( ref A045). B: Elimination of a sulfinic acid. C: Sigmatropic elimination of N2
(stereospecific delivery of a hydride via a concerted mechanism).
C066
BrMg

O O O O
N A N N B N
Me O Me O Me Me MgBr
MgBr

BrMg
H H

O
C N N OMgBr N OMgBr
Me MgBr Me Me

BrMg
H workup
+H+
N N N
H
Me Me MgBr Me
Bosco, M.; Dalpozzo, R.; Bartoli, G.; Palmieri, G.; Petrini, M.
J. Chem. Soc., Perkin Trans. 2 1991, 657.
Bartoli indole synthesis. A: Reduction of the nitro group by means of addition of CH 2=CHMgBr and
elimination of an enolate to form a nitroso compound. B: Addition of CH2=CHMgBr to the nitroso
group. C: [3,3] Sigmatropic rearrangement.

C067
O TiCl4
Cl4Ti Cl4Ti O
O O Me
H C N Me
Cl A N B
Me Me Me O

TiCl4 TiCl4
O O Me O
Me
Me Me
N O N
N
Me O
O Me

Yoon, T. P.; Dong, V. M.; MacMillan, D. W. C. J. Am. Chem. Soc. 1999, 121, 9726.
A: Formation of a ketene. B: Aza-Claisen rearrangement through a chair-like transition state.
C068

S S S Zn
TBSO Cl TBSO A TBSO AcOH
O Cl O
O A
Cl Cl Cl
Cl

S HF S workup S
H
TBSO t-Bu O HO
O Si O O
Me Me
F

CSA S -H+ SH -H+ O

HO O
+H+ O +H+ +H+ HS O
HO
H B

Vedejs, E.; Buchanan, R. A. J. Org. Chem. 1984, 49, 1840.

A: [3,3] Sigmatropic rearrangement. B: Intramolecular acyl transfer reaction.

C069

H
OMe OMe N
(OC)4Cr (OC)4Cr Bn
C Me A Me Me
O O O A
(CO)4Cr OMe

Me
N N Me N Me
OMe B
Bn Bn OMe Bn OMe
O O O

I I H I H I
H H
I2
N Me N Me N Me
Bn OMe C OMe OMe
O Ph O O
I

eur, C. J.; Miller, M. W.; Hegedus, L. S. J. Org. Chem. 1996, 61, 2871.
A: Photo-induced insertion of CO to form a ketene. B: Aza-Claisen rearrangement. C: Intramolecular
iodoamidation followed by debenzylation in an SN2 fashion.

C070
OH
OH
R
Me R
Me O OH +
Me -H O
Me O Me
O O Me Me
A +H+
Cl O O Me
O Me B
O
O
OH
O
Me Me
R O + O
-H OH
O e O
O O
OH +H+ O MeM O
Me D E
Me Me C R R
Cl
O O

O Me O Me O
NaOMe O
R R OMe R R
Cl Cl Cl
Schreiber, S. L.; Sammakia, T.; Uehling, D. E. J. Org. Chem., 1989, 54, 15.
A: Activation by cyclization. B: Formation of an orthoester followed by cleavage of the five-membered
lactone. C: Intramolecular interception of the stable carbocation by the secondary alcohol. D:
Cleavage of the resulting orthoester. E: SN2 reaction at the less hindered carbon with chloride ion.

C071
F3B Bn
F3B O N
O O
R H + BF3
O -H
H
NHBn N R
H
CO2Me CO2Me
N
H

NBn NBn
-H+
A H
N R N R
H H
CO2 e
M CO2 e
M
 NBn NBn NBn
H

N R N R N R
H H H
CO2Me CO2Me CO2Me

NBn NBn
-H+
B H
O
N R N
H H
CO2Me CO2Me

Parsons R. L.; Berk J. D.; Kuehne M. E. J. Org. Chem. 1993, 58, 7482.
A: Mannich reaction followed by [3,3] sigmatropic rearrangement. B: Mannich reaction.

C072
Br
CN
N N NaH N
H OH OH O
NC NC

mCPBA MeOH
N N N
O O A O O
OH O
H
NC H

H H2, Pd/C H
N N
B O
Me Me

O'Neil, I. A.; Cleator, E.; Ramos, V. E.; Chorlton, A. P.; Tapolczay, D. J.

Tetrahedron Lett. 2004, 45, 3655.
A: Cope elimination. B: Retro Cope elimination.

C073
O O TMS O TMS
H OR
O Me O O O
O H O
A

TMS
 O O
O O
O TMS
TBAF
O H H
O SiMe3
B C
H O H OTMS

O O O
O O O

workup
H H H
F +H+

H O SiMe3 H O H O

Ovaska, T. V.; Roses, J. B. Org. Lett. 2000, 2, 2361.

A: 5-exo-dig Cyclization of the alkoxide ion. B: Claisen rearrangement. C: Migration of the silyl group
to form a silyl enol ether.

C074

S N S N S N O
H O N2
A
N2
OH
H OH
RhLn

N RhLn
N2 Rh2(OAc)4 N
S N S N S N N N
B
O O O

S RhLn S
RhLn O
S N
C N O N
O

S SH
H Raney Ni
O O O
D N N E N

Fang, F. G.; Prato, M.; Kim, G.; Danishefsky, S. J. Tetrahedron Lett. 1989, 30, 3625.
A: Conjugate addition of a thiolactam anion. B: Formation of a rhodium carbene complex. C: Attack
of the sulfur atom to the rhodium carbene complex followed by formation of a thiirane. D: Cleavage of
the thiirane assisted by the nitrogen lone pair. E: Desulfurization.

C075
O O
O O O O
Me OMe -H+
Me OMe Me OMe RhLn
A OH B
N N RhLn
RhLn N
N Me Me

O O Me O HO M
e O
+H+
Me
Me OMe HO OMe OMe
LnRh C
O O O

Me Me Me Me Me

OH F3B
O Me O Me
O BF3-Et2O
Me Me MeO MeO
D Me Me
MeO O O Me OH O Me OH

H F2B Me H Me
O O
Me O BF3 Me O HO
or MeO O
Me Me E
Me MeO O Me MeO O O Me

Drutu, I.; Krygowski, E. S.; Wood, J. L. J. Org. Chem. 2001, 66, 7025.
A: Formation of a rhodium carbene complex. B: Addition of an alcohol to the carbene complex. C:
Formation of an (Z)-enol. D: [3,3] Sigmatropic rearrangement via a chair-like transition state. E: 1,2-
Migration through a synperiplanar transition state.

C076

F3B F3B
O O Me
O O Me O
O workup
A +H+
SnMe3 SnMe3

SnMe3
 AcO OAc
H Pb
Me Me AcO OAc Me
O
O O O
O -H+ HO O Pb(OAc)4 H O O
+H+
SnMe3 B SnMe3 SnMe3

AcO OAc Me
Pb O Me O
-H+ AcO O O O
O (Ph3P)3RhCl
O
A Me
SnMe3

Posner, G. H.; Wang, Q.; Halford, B. A.; Elias, J. S.; Maxwell, J. P.

Tetrahedron Lett. 2000, 41, 9655.
A: Attack to the epoxide takes place from the less hindered side to form the trans-product. B:
Formation of a hemiacetal. C: Oxidative fragmentation induced by Pb(OAc)4.

C077

O H n-Bu O
O
A

Me Me Me

HO H
workup
O
B +H+

Me Me
Sayo, N.; Kimura, Y.; Nakai, T. Tetrahedron Lett. 1982, 23, 3931.
A: [2,3] Wittig rearrangement. B: Oxy-Cope rearrangement.

C078
C6H11 C6H11
N N
CHO O Et3N AcO
-H2O H
R R AcCl R

A B
O O O
O Me O Me O Me
Me Me Me
 C6H11
N C6H11
O NaOAc
N OAc OHC OAc
-H+ R R aq AcOH R
Me O

O O O
O Me O Me O Me
Me Me Me
Vosburg, D. A.; Weiler, S.; Sorensen, E. J. Angew. Chem. Int. Ed. 1999, 38, 971.
A: Formation of a nitrone. B: Acetylation followed by [3,3] sigmatropic rearrangement.

C079
OTBS
Me
OH OH OH
HO -DMSO
O
R R H R
A O B O C O
O O
OTBS O SMe2 O SMe2 O
O O
OTBS OTBS
Me Ac2O Me
-H+ HO Et3N AcO DBU
O O
+H +
toluene
D OTBS OTBS 100oC
O O

OTBS OTBS OTBS

Me Me Me
AcO
O O O
E
H OTBS OTBS OTBS
O O O

TBSO
H
O
F OTBS
O
Bauta, W. E.; Booth, J.; Bos, M. E.; DeLuca, M.; Diorazio, L.; Donohoe, T. J.; Frost, C.; Magnus, N.;
Magnus, P.; Mendoza, J.; Pye, E; Tarrant, J. G.; Thom, S.; Ujjainwalla, F.
Tetahedron. 1996, 52, 14081.
Achmatowicz reaction (A-D). A: Diels-Alder reaction of singlet oxygen. B: Reductive cleavage of the
endoperoxide with Me2S. C: Elimination of DMSO to form cis-enal. D: C yclization to form a lactol.
E: Generation of a pyrylium ion (or a carbonyl ylide). F: 1,3-Dipolar cycloaddition.
C080
Et3N
O O O O
H C hv
Cl
A C B C
O O O

O O
-CO

D
O O O O

-CO

E
O O
Turro, N. J.; Leermakers, P. A. Vesley, G. E Org. Synth., Coll. Vol Ⅴ 1973, 297
A: Formation of a ketene. B: [2+2] Head-to-tail dimerization of a hindered ketene. C: Norrish type I
cleavage of the ketone followed by decarbonylation to form a diradical. D: Recombination of the
diradical.

C081

TiCl4
O TiCl4 O
Me Me
SiMe3
C A
Me Me Me

TiCl4
O O
Me Me Me
Me
SiMe3 SiMe3

H
Me Me
Danheiser, R. L.; Fink, D. M.; Tsai, Y.-M. Org. Synth., Coll. Vol. Ⅷ 1993, 347.
Danheiser annulation. A: Conjugate addition of the allenylsilane to form a carbocation stabilized by
the silicon atom.
C082
Ph2P Cl O
n-Bu
Et O H Et O Et O PPh2

Ph Me Ph Me A Ph Me Me Me
O
O Me
Me
H O Ph O OH
O O Ph2P
Ph2P Et O Me
B Et O Me Ph Me O
Ph Me
O Ph

O Me
Ph O Et
+ O OH
C Ph Me O PPh2
Me

Mukaiyama, T.; Shintou, T.; Fukumoto, K. J. Am. Chem. Soc. 2003, 125, 10538.
A: Formation of a phosphinite ester. B: Addition of the phosphinite to the electron-deficient quinone.
C: SN2 reaction with inversion of configuration.

C083
OMe Me OMe Me
MeO Cl MeO Cl

H A
BnO TMS BnO
N
TMS

OMe OMe
MeO MeO O3

B Me Ph3P
C
H
Me
BnO BnO
 O OMe
MeO MeO
TsOH
Me
MeO -H2O
O O
D

BnO
Bn
Taber, D. E; Neubert, T. D. J. Org. Chem. 2001, 66, 143.
A: α-Elimination to form an alkylidene carbene. B: C-H insertion at the kinetically favored position. C:
Ozonolysis. D: Intramolecular aldol reaction.

C084
H
O N
H N Bn
N O Ns
N Bn A
Ns Bn N C O

O
BnHN BnHN
Bn O O
NH -H+
N N N
O +H+ N Bn N Bn
Ns Ns Ns
N O
Bn O O

O O
NHBn NHBn
Ns H N Bn -H+ -H+
N
B O +H+ H N Bn +H+
NHNs O
HO O
NHBn NHBn
-H+
N Bn +H+ N Bn
NsHN NsHN
O O
Paulvannan, K. J. Org. Chem. 2004, 69, 1207
A: Ugi reaction ( ref C007). B: Intramolecular Diels-Alder reaction followed by β-elimination to
release the ring strain.
C085
workup
Me Me Me Me Me Me
Me Li Me +H+ Me
O O HO

Me
SOCl2 Me Me Me Me Cl
Me Me
HO O A Me
Cl S Cl Cl Me
S O
O Cl
Me Me
Mg MgCl 60oC Me MgCl MgCl
B Me C
Me Me Me
Me H MeH

O
Me Me Me
OHC MgCl workup
OMgCl +H+ OH
Me Me Me
MeH MeH MeH

Oppolzer, W.; Bättig, K. Tetrahedron Lett. 1982, 23, 4669.

A: Formation of an allyl chloride via SN2' reaction. B: Formation of a Grignard reagent. C:
Magnesium-ene reaction through a chair-like conformation.

C086
O Ph
P H P H P
Ph OEt A O
Ph Ph Ot-Bu Ph Ph Ph Ph
OEt

O Ph
Ph
EtO P Ph
P
B O C
Ph Ph Ph
OEt

O Ph O
EtO P Ph P Ph
Ph
Ph EtO Ph

Fujimoto, T.; Kodama, Y.; Yamamoto, I.; Kakehi, A. J. Org. Chem. 1997, 62, 6627.
A: Conjugate addition of an ylide. B: Intramolecular proton transfer to generate an ylide. C:
Intramolecular Wittig reaction.

C087
O
I C
I I PdLn PdLnI
Pd(0) CO
H
N B NTs NTs NTs
Ts

PdLnI O O

O PdLnI
A B C PdLnI
NTs NTs NTs

O O
CO PdLnI
D LnPd
O I
NTs NTs

O O O
-Pd(0) O
E
N N
Ts Ts
von Seebach, M.; Grigg, R.; de Meijere, A. Eur. J. Org. Chem. 2002, 3268.
A: Pd-mediated carbonylation to form an acylpalladium species. B: Carbopalladation to a strained
olefin. C: β-Carbon elimination. D: Intramolecular carbopalladation to the resulting strained olefin. E:
Reductive elimination of the palladacycle.

C088
O O HO
Me workup Me HBF4
Me SPh SPh
SPh +H+ +H+
 H
H O Me Me H2O Me
Me SPh -H+
SPh
A +H+ OH
SPh S
Ph
H

Me LiBH(s-Bu)3 Me
Me
MeLi, KOEt
B H C
O O OH
Bs-Bu3

Me
Me Me Me
workup

+H+

OH O OH

Danheiser, R. L.; Martinez-Davila, C.; Sard, H. Tetrahedron. 1981, 37, 3943.

A: Pinacol-type rearrangement. B: Reduction of the ketone. C: Anion-accelerated vinylcyclobutane-
cyclohexene rearrangement.

C089
Boc Boc Boc Boc
N N N N
workup
O O OH
O
A B +H+
H H

Boc S Boc Boc

N N N
KH C
O O S H3C I O SMe
S
S S

Bu3SnH Boc Boc Boc

N N N
AIBN
O SMe O SMe
C S S
SnBu3
SnBu3

Boc Boc
N N
NBoc
D
H SnBu3
 Hodgson, D. M.; Maxwell, C. R.; Wisedale, R.; Matthews, I. R.;
Carpenter, K. J,; Dickenson, A. H.; Wonnacott, S.
J. Chem. Soc., Perkin Trans. 1 . 2001, 3150.
A: α-Elimination of the epoxide to form a carbene. B: C-H insertion. C: Barton-McCombie
deoxygenation of a xanthate ( ref A051). D: Formation of a radical at a cyclopropylcarbinyl position
induces cleavage of the cyclopropane ring (cf. radical clock).

C090
Me Me Me

N -H+ N N
H H H OH2
+H +
OH HO HO HO
R R R

Me Me
R
N N N
A B
HO O
O
R R Me

Angle, S. R.; Fevig, J. M.; Knight, S. D.; Marquis, R. W., Jr.; Overman, L. E
J. Am. Chem. Soc. 1993, 115, 3966
A: Aza-Cope rearrangement. B: Mannich reaction.

C091
Cl3Sn Cl

O O Cl3SnO O RO Cl3SnO O OR
N N N

Me Me A Me
Ph Ph Ph

O O OR O O OR
workup N NaHCO3 N

Me benzene Me A
Ph reflux Ph
 Ph NiCl2
N O HO O H
O NaBH4 -ROH
H
Me OR
Ph B
H2N
H Me Ph

HO O HO O HO OH
workup
H
+H+
H2N H2N H2N
Me Ph H Me Ph Me Ph

Denmark, S. E.; Dixon, J. A. J. Org. Chem. 1998, 63, 6178.

A: In verse electron demand hetero-Diels-Alder reaction. B: 1,3-Dipolar cycloaddition. C: Reductive
cleavage of the N-O bonds.

C092
Me Me Me Me

BnO BnO BnO BnO

A B S
O O O
H S N O
Et3N N O
S N O
Cl
O

BF3-Et2O
Me Me Me
H2O OH2 -SO2
BnO BnO BnO
C
S H S
N O O O
BF3
O

Baudin, J.-B.; Julia, S. A. Tetrahedron Lett. 1988, 29, 3251.

A: Formation of a morpholinesulfenate. B: [2,3] Sigmatropic rearrangement. C: Extrusion of SO2
through a six-membered transition state.

C093
HO
Tf 2O
OTf
pyridine A
O CO2Et
EtO2C Mo(CO)5
Me
 Mo
Mo(CO)5 Mo(CO)5
O B O O (CO)5
Me Me Me
CO2Et
CO2Et CO2Et

H
H H
H
C Mo D E
O (CO)5 O Me O
Me CO2Et Me
CO2Et CO2Et

Harvey, D. E; Brown, M. F. J. Org. Chem. 1992, 57, 5559.

A: Formation of a Fischer carbene complex. B: Intramolecular alkyne metathesis. C: Intramolecutar
alkene metathesis. D: Reductive elimination to form a cyclopropane. E: Divinylcyclopropane
rearrangement ( ref A042) via a boat-like transition state.

C094

Me H Ot-Bu Me O
O O
Me O3
Me Me
Me
Me Me
Br Br Me

O O O
O O Me Me Me
O MeOH
Me O Me Me
A O O
Me O Me Me
O

O Me

Me Et3N MeO Me
-H + Ac2O
MeO Me O Me
+H + O
O Me
HO MeO O OMe

O O
 O O
Et3N O
Me Me Me
H
CO2Me
MeO Me MeO Me
B
O Me O Me Me Me
AcO AcO
Srikrishna, A.; Anebouselvy, K.; Reddy, T. J. Tetrahedron Lett. 2000, 41, 6643.
A: Ozonolysis of the less hindered olefin in MeOH to form a hydroperoxide ( ref Bl16, Bl17). B:
Grob-type fragmentation.

C095
H
H Me H Me H Me

O O
Me Me SiMe3 Me OSiMe3
Me3Si OTf

Me Me
Me H
H H H
H H
OSiMe3 OSiMe3
Me OSiMe3 Me Me
Fujita, T.; Ohtsuka, T.; Shirahama, H.; Matsumoto, T. Tetrahedron Lett. 1982, 23, 4091
Wagner-Meerwein rearrangements.

C096
MeO MeO MeO MeO
H
Ph
O A O OH B OH
Me Me Me Me

H
MeO H OMe MeO OH O
H3O+
OH2
OH C OH OH OH
Me Me Me Me
 TsOH O O OH2 O
H2O -H2O -H+ OH
OH2 D
Me Me Me
Dechoux, L.; Agami, C.; Doris, E.; Mioskowski, C. Eur. J. Org. Chem. 2001, 4107.
A: α-Elimination of the epoxide to form a carbene. B: Cyclopropanation. C: Cleavage of the electron-
rich cyclopropane ring. D: Cleavage of the cyclopropane ring.

C097
Me3Si Me3Si Me3Si
CO2Me Br CO2Me Br CO2Me
Br Br
A
CO2Me O
O OMe O CH3 Br

Me3Si Me3Si
Br CO2Me Br CO2Me CO2Me
AgNO3 A
g
O MeOH O B O
O O O

O OH
O MeOH TFAA
CO2Me
DMSO
CO2Me CO2Me C

Me O O
S Me Me
Me CF3 S
OH O
H O
CO2Me CO2Me CO2Me

CO2Me CO2Me CO2Me

Fleming, I.; Michael, J. P. J. Chem. Soc., Perkin Trans 1 .1981, 159.

A: Bromolactonization. B: Wagner-Meerwein rearrangement followed by desilylation. C: Swern
oxidation.

C098
HO
O N
NH2OH

CN CN -H2O CN CN
 N
A
HO H
N O
160oC N

CN A
N CN

CN CN

O O
N N NC
N
CN
B O
CN CN

Stockman, R.A. Tetrahedron Lett. 2000, 41, 9163.

A: Formation of a nitrone by intramolecular Michael addition of the oxime to the α,β-unsaturated nitrile.
B: Intramolecular 1,3-dipolar cycloaddition.

C099
TBS TBS TBS
O O O
O O
O HBF4
OH OH OH
A Ph2S B
Ph2S
H H H H H H

TBS TBS TBS

H O
O O O PhSSPh
O OH
-H+ NaOMe
OH OH OH

H H H H H H

MeO TBS PhS SPh TBS TBS

O O O
O O O
H PhS
OH OH OH

H H H H H H
 TBS TBS TBS
O O O
PhS O PhS O O
PhS PhS workup PhS
H O O O H
PhS
+H+
MeO H H H H C H H

Kwon, O.; Su, D.-S.; Meng, D.; Deng, W.; D'Amico, D. C.; Danishefsky, S. J.
Angew. Chem. Int. Ed. 1998, 37, 1880.
A: 1,2-Addition of the sulfur ylide followed by formation of an epoxide in an SN2 fashion. B: Cleavage
of the epoxide induces 1,2-migration to form a cyclobutanone via a stable tertiary carbocation. C: Ring
opening of the cyclobutanone by the proximal alkoxide is facilitated by formation of the sulfur-stabilized
carbanion.

C100
Cl
S CO2Me CO2Me CO2Me
Cl
S
S
Me OTs Cl OTs OTs
Me Me
A
N CO2t-Bu N CO2t-Bu N CO2t-Bu
Boc Boc Boc

CO2Me B H CO2Me CHO2Me

Cl Cl Cl
SO2 SO2 SO2
mCPBA KOMe
Me OTs Me OTs Me OTs

N CO2t-Bu N CO2t-Bu N CO2t-Bu

Boc Boc Boc

Cl Cl SmI2 Cl m
O2 O O2 O O2 O S I2
S S S
Me Me SmI2 Me Me Me Me
H H H H H H
B C
N CO2t-Bu N CO2t-Bu N CO2t-Bu
Boc Boc Boc

Cl m
O S I2

-SO2 Me Me workup Me CO2Me

H H
D +H+
N CO2t-Bu N CO2t-Bu
Boc Boc
 Bachi, M. D.; Melman, A. J. Org. Chem. 1997, 62, 1896.
A: Formation of an episulfonium salt followed by attack of chloride ion at the less hindered carbon. B:
Cyclization proceeds by an SN2 mechanism. C: SET. D: β-Cleavage followed by extrusion of SO2
and elimination of a chloride radical.

C101
MeO MeO MeO

H H
H
A B C

S S S

OMe
hv
D
S OMe S

Wu, J.-Y.; Ho, J.-H.; Shih, S.-M.; Hsieh, T.-L.; Ho, T.-I. Org. Lett. 1999, 1, 1039.
A: Photo-induced 6e conrotatory etectrocyclic reaction. B: Thermally allowed suprafacial
1,9-hydrogen shift. C: 6e Electrocyclic reaction. D: Photoisomerization of the (Z)-olefin.

C102
BF3 Me3SiO Me3SiO
EtO OEt OEt EtO
X
Me3SiO O SiMe3
A

Me3SiO Me3SiO
EtO Et O
CF3CO2H H
O O
+H+

X
Me3SiO
O Me3Si O O O O
B

Nakamura, E.; Kuwajima, I. Org. Synth., Coll. Vol. Ⅷ 1987, 17.

A: Mukaiyama aldol reaction. B: Preferential migration of the carbonyl carbon (Pinacol
rearrangement).
C103
OH OH
O N HN
H NH2OH H NaBH3CN H

-H2O
Me Me Me
H H H

O
N
HCHO H N MeOSO2F
O Me
-H2O B
Me
A H
O F
Me S
Me
O O Me H
N N N
LiAlH4
O Me O Me Me
HO

Oppolzer, W.; Petrzilka, M. J. Am. Chem. Soc. 1976, 98, 6722.

A: Formation of a nitrone. ref A065. B: 1,3-Dipolar cycloaddition.

C104
CO2Et CO2Et
MeO
O Ar O O

MeO O O Me OAc
AcO H

OAc
CO2Et CO2Et

Ar OAc A Ar
H C
O
AcO O

AcO CO2Et AcO CO2Et

O MeO
B Ar
O Me OAc OAc
MeO
 O H OH
AcO OEt AcO C OEt
Ar OAc C OAc
Ar
O O
CO2Et CO2Et
AcO CO2Et
OAc
AcO AcO AcO
Ar H D Ar C E F
O Ar
O
AcO O

AcO
H H
CO2Et CO2Et AcO CO2Et
AcO AcO
AcO O AcO MeO
Ar Ar
O Me OAc OAc OAc
MeO

Serra, S.; Fuganti, C. Synlett. 2002, 1661.

A: Generation of a ketene via a mixed anhydride. B: Benzannulation. C: Michael addition. D:
Formation of a ketene. E: 6e Electrocyclic reaction. F: Michael addition.

C105
Me Me Me
Me Me Me
O O O
O O O
Me Me Me
O A O O

O O Me H
Me Me
Me Me
O O H
Me Me O
O O H
Me Me O O

Me H
H2
Pd/C
H
O
B H
Me Me O O

Singh, V.; Prathap, S.; Porinchu, M. J. Org. Chem. 1998, 63, 4011.
Oxa-di-π-methane rearrangement. A: n-π* Transition. B: Reductive cleavage of the cyclopropane
ring.
C106
Ph Ph Ph
Ph -N2
N
O N A O N N B N N
O O O
O H

H Ph
Ph H
Ph Ph
O O O

C D E H
O
OH OH OH OH
Lee, H.-Y; Kim, Y. J. Am. Chem. Soc. 2003, 125, 10157.
A: Thermal decomposition of an a ziridinylimine to form a diazoalkane. B: Cleavage of the epoxide
followed by elimination of N2 to form an alkylidene carbene. C: C yclopropanation. D: Homolytic
cleavage of the strained cyclopropylidene ring to form a trimethylenemethane diradical. E: Radical
addition.

C107
H

Cl -H+
Cl Cl
Cl A
S S S

-S
Cl
B Cl C Cl
S S

Parham, W. E.; Koncos, R. J. Org. Chem. 1961, 83, 4034.

A: 2e Electrocyclic reaction. B: 6e Disrotatory electrocyclic reaction. C: Spontaneous loss of S.

C108
O H O O

NH N N
H
CN H CN H CN
 OH H H
ClCO2Me
N N N
A O O
Cl OMe
O OMe
O

H N H
H
KOH
N OMe
N OMe O
O O
O O OMe
O OMe
H H

N OMe N OMe
O O
O O
H OMe
Earley, W. G.; Jacobsen, E. J.; Meier, G. P.; Oh, T.; Overman, L. E.
Tetrahedron Lett. 1988, 29, 3781.
A: Anion-accelerated aza-Cope rearrangement.

C109

mCPBA O HBF4 O H
TBSO TBSO TBSO
A

O
OH +
-H BrMg Me
TBSO TBSO
B C workup

Cl PdCl Cl
Me Me Pd
Me O
OH OH
PdCl2
TBSO TBSO TBSO
D
 ClPd
H Me O H PdCl Me O

TBSO TBSO
E F G

Cl
H H
Pd Me O -HCl Me O
Me
-Pd(0)
TBSO TBSO

Nemoto, H.; Miyata, J,; Yoshida, M.; Raku, N.; Fukumoto, K.

J. Org. Chem. 1997, 62, 7850.
A: Epo xidation of the strained olefin. B: Cleavage of the epoxide to form a stable benzylic cation. C:
1,2-Migration to form a cyclobutanone ( ref A099). D: Ring expansion reaction initiated by o xidation
of the olefin with PdCl2. E: Intramolecular carbopalladation. F: β-Elimination. G: Reversible
hydropalladation and 6-elimination process to give the more stable endocyclic olefin.
 附 录

有机反应机理书写的考虑要素

1．考虑反应机理时重要的电负性值

有机反应按样式可分为自由基反应，极性反应，周环反应，反应中占有比例最多的反应
时极性反应，就是在反应体系中的电子的丰富的体系中，与缺乏电子的体系相互吸引，生
成的化学键结合，切割的进行的反应。电子在书写时被我们用“弯箭头”介入那里，代表
电子的移动。

电子从富电子体系向电子缺少体系移动。那么，如何成为判断电子如何移动的线索之一
就是是电负性值。电负性值是电子吸引的内在量度，那个值越大，对电子的吸引力就越
强。例如，一溴甲烷中，电子被吸引到溴原子一边，碳会部分地带正电（δ+），而溴原
子会部分带负电荷的（δ- ）。一溴甲烷和乙醇钠（的NaOEt）的反应时，具有负电荷的
氧原子会接近具有部分正电荷的碳原子，形成C-O键。然后C-Br键断裂，孤对电子移动到
溴原子上，就产生了溴离子。

δ δ
－ +
Br CH3 Na OEt Na Br + H3C OEt

再来看看羰基化合物的反应，羰基中的电子被吸引到电负性值较大的氧原子上，碳带正
电，氧带负电。富含电子的亲核试剂，像烷氧基一类的，会接近具有部分正电荷的碳原
子，并生成新的键。此时，C-O键上的电子是在向氧原子移动。另一方面，羰基化合物在
与盐酸那样的Brønsted酸反应时，带负电的氧原子与带正电质子（H+）发生反应，使原先
带负电的结构发生极化。这样的极化导致了C-O键的分极，于是将提高对亲核基团的反应
活性。
 R' H
O O O O O
+ O R' H
C C C
R R R R R R R R

因此考虑化合物中的官能团的电荷——最具反应性的位点，是考虑反应机理的基础。

表①常用元素电负性一览表
H
2.1
Li Be B C N O F
1.0 1.5 2.0 2.5 3.0 3.5 4.0
Na Mg Al Si P S Cl
0.9 1.2 1.5 1.8 2.1 2.5 3.0
K Ca Br
0.8 1.0 2.8
I
2.5

2.从酸度系数pKa预测反应途径
在水溶液中酸性化合物的电离方式如下。

HA + H2O A- + H3O+

对于HA酸放出质子后的A-，叫做HA的共轭碱。此时测量出的它的酸性量度，就是我们
常用的酸度系数。在稀的水溶液中，化合物的酸离解常数（pKa）定义为如下。

 A   H3O 
- +

pKa =
- log Ka =
[ HA ]

根据这个定义，pKa的值就越小，酸性越大，（由于平衡偏向右边，化合物很容易释放
出质子）。同时还要考虑到共轭碱（B）在共轭酸的pKa（HB +）的值较大时，碱性就会高
（平衡偏向左边，化合物难以释放质子）。
酸（HA）与酸根（共轭酸HB碱B-）共存时，平衡常数为Keq的酸和酸根的pKa的数值
可以表示如下。
 -
HA + B A- + HB
 A  [ HB]
−

− log   − =
pKeq = pKa ( HA ) − pKa ( HB )
[ HA ]  B 

也就是说，只是通过计算的两种酸的pKa的差，严格意义上来说是不准确的，有可能会
遗漏溶液中的平衡状态。例如，丙二酸二乙酯（EtO2CCH2CO2Et;pKa值=13），乙醇钠（乙
醇钠，共轭酸乙醇0）时的pKa=16）共存，可以大致考虑平衡如下。

O O O O

EtO OEt + EtO EtO OEt + EtOH

H

pKeq=pKa ( malonate ) - pKa ( EtOH ) =13 - 16=-3

Keq=103

这种平衡可以看出它偏向右侧。从另一种化学的角度来看，丙二酸二乙酯是一种弱酸，
乙醇钠是一个强酸根，这导致它几乎完全脱去质子。
接下来，考虑以下的反应。生成的是二异丙基氨基锂（LDA）。正丁基锂（是pKa=50共
轭酸正丁烷）拔出二异丙胺的质子（pKa值=36），以生成LDA。然后LDA是拉出的酯的α
碳的质子（pKa值=24），以生成酯的阴离子。将这种阴离子和苯甲醛缩合，得到的产物
共轭酸的pka变小了（pKa值=17）。在后面的反应里加入乙酸（pKa值=4.8），醇盐被质
子化，产生了具有乙酸阴离子的产物，反应才结束。如下所述，pKa值高的试剂不断反应
生成pKa值低的试剂，使反应顺利进行。

i-Pr n-BuLi i-Pr

N H N Li (LDA)
i-Pr i-Pr
 LDA;
O O OH
PhCHO;
EtO CH3 AcOH EtO Ph

n-Bu i-Pr2NH
36
O
n-BuH i-PrN
50 EtO CH3
24
O O
i-Pr2NH
EtO CH2 H Ph
O O

EtO Ph AcOH
4 .8
O OH
AcO
EtO Ph

另外，pKa值也是共轭碱的脱去能力的量度。虽然不能直接表示基团的脱去能力——它们
只是pKa为酸电离的平衡状态的数字表示，但是pKa值和脱去能力之间有很多的相关性。例
如，一个羟基的取代反应，通过正常的亲核基团，羟基的取代反应几乎不能进行，但由于
甲磺酰基的作用，反应可以很轻易地引入亲核基团。这可以从水（pKa值= 15.7）和甲磺酸
（pKa值= -6）的pKa的比较中来理解。

MeSO2Cl
Et3N O Nu- O
HO R Me S O R Me S O + Nu R
CH2Cl2
O O

事实上反应机理是由各种因素决定的，而不是仅仅是由pKa决定反应如何进行，从pKa值
的大小来观察也可能进行逆向的去质子化反应。从酸度系数的定义严格地来说，它不能准
确描述反应的状态。但是，从pKa值的大小来比较出反应的结果，是考虑反应机理时非常
有效的方法。在卷末对pKa值有一个总结表，一定要好好利用。
 表② 酸度系数
pKa 酸 酸根 pKa 酸 酸根
O O O O
-10 HO S OH HO S O -1.4 N OH N O
O O O O

O O
OH OH
-9 -0.5
R Cl R NH2
R Cl R NH2

O O O
OH
-8 0.5
R H F3C OH F3C O
R H

OH O O O
-7 1.5 S S
R R R R Ph OH Ph O

O O O O
-6.5 r
A S OH r
A S O 2.0 HO S O O S O
O O O O
O O
-6.4 ArOH2 ArOH 2.2 HO P OH HO P O
OH OH
O O O O
-6 Me S O Me S OH 2.9
ClH2C OH ClH2C O
O O

OH O O O
-6 4.2
R OH R OH Ph OH Ph O

H O O
-6 Ar O R 4.8
Ar O R Me OH Me OH

HO O
H
-3.5 R O R 6.4 C O C O
R O R HO HO

-2.4 EtOH2 EtOH 10.0 PhOH

PhO

-1.7 H3O H2O 11.6 HO OH HO O

O Me Me
OH
-1.5 12.2 NOH NO
Ar NH2 Me Me
Ar NH2
 A aminonitrile A011
abnormal Claisen rearrangement C032 Arbuzov reaction A070
acetal ate complex A028, B002
A008, A009, A010, A063, B084, B 116 atom transfer reaction B033, B038, C028
Achmatowicz reaction C013, C079 aziridine B101, Bl19
acid chloride A003, A025 aziridinylimine C 106
acyl azide A058 azirine B056, B080, C038
acyl cyanide B061, C050 azlactone A019, C009
acyl transfer
B007, Bl13, Bl14, C007, C035, C068 B
acylation B060, C012, C029, C050 Baeyer-Villiger oxidation A054
acyliminium ion C041, C051 Bartoli indole synthesis C066
acylium ion A003, A036, B068 Barton reaction B097, C014
acylnitroso compound B120 Barton-McCombie deoxygenation
acyloin condensation Bl15 A051, B071, C089
acylpalladium species C087 Beckmann fragmentation A015
addition Beckmann rearrangement A055, C014
1,2- A016, C042, C099 benzannulation C 104
conjugate benzyne B012, B065
B046, B094, C006, C019, C086, C029 Birch reduction A038, A039, B011
intramolecular Bischler-Napieralski reaction A034
A008, A010, A021, A049, A052, B008, B012 bromination
to carbonyl group A010, A024, A025, A027, B087, C036, C063
A001, A002, A003, A004 Brook rearrangement C042
to electron-deficient aromatic ring
A040, B022 C
addition-elimination C002 Cannizzaro-type reaction B052, C026
aldol reaction A020, B052, B053, Bl13 carbamate-type protective group for amines
aldol reaction intramolecular B019, B020, B021
C025, C027, C083 carbanion B006, B047, B049, C099
1, 2-alkyl shift carbene A059, A061, B075, B103, C021,
A036, A047, A048, A054, B119, C004, C063 C064, C089, C096
allene A061, B028 alkylidene B036, B049, C016, C037,
allenylpalladium species C060 C054, C055, C083, C106
allenylsilane C081 dialkoxy- C046
rc-allylpalladium complex dibromo- A061, B075
B021, B040, C060 dichloro- A035, B076
allylsilane B078, C051 carbocation
A030, A036, A046, A047, A048, A049, B015, of S--N bond C048
B023, B051, B068, B078, B085, B108, Bl19, of S-O bond C048
C063, C070, C081, C099, C109 of thiirane C074
carbon monoxide B042, B068, B127, C069 of c~-lactone B081
carbonyl oxide C049 oxidative A044
carbonylation C087 reductive A029, B035, C079, C091, C105
carbopalladation A075, C010, C087 Cope elimination A053, C072
carbotitanation B128 Cope rearrangement C040
cation cyclization B108 aza- B092, C090, C108
cation-olefin cyclization C003, C056 oxy- C004, C077
C-H insertion B036, B049, B075, Corey-Fuchs reaction B049, B077
B080, C016, C038, C083, C089 Corey-Winter olefination B103
charge-transfer complex B063 CSI (chlorosulfonyl isocyanate) B064
cheletropic reaction B030, B080, B101 Curtius rearrangement A058
chlorination B089 cyanohydrin B005
Claisen condensation C045 cyclization
Claisen rearrangement 5-endo-trig C019
A062, A063, B094, C009, C024, C062, C073 5-exo-dig C073
aza- C017, C067, C069 [2 + 2] cycloaddition C052, C054, C080
Claisen-Ireland rearrangement B093, B124 cyclobutane A066
Claisen-Johnson rearrangement B091 cyclobutanone C099, C109
Claisen-Schmidt reaction C038 cyclopropanation C106, B075,
cleavage B004, B070, B103, C046, C076 B076, B126, C021, C042, C046, C055, C096
heterolytic A029, B 116, B 117 cyclopropane A061, B128, C020, C093
homolytic B018, B038, B039, B069, cyclopropanone A060
B080, B097, C055, C106
of azirine ring C038 D
of C-N bond C012 Dttz reaction B127
of C-S bond B044 Dakin reaction A056
of cyclobutane ring C052 Danheiser annulation C081
of cyclobutene B054 DCC (N,N'-dicyclohexylcarbodiimide)
of cyclopropane ring A060, B015,B084, A007, B014
C020, C043, C046, C089, C096 decarboxylation
of cyclopropanone B057 A023, A039, A057, B001, B019, B051, C023
of endoperoxide B034 dehydration B062
of epoxide B003, B023, B051, B071, deprotonation A002, A019
B102, Bl10, C001, C006, C013, C099, Ct06, desulfurizatio B103, C074
C109 diazo coupling A037
of four-membered ring C059 diazo transfer reaction B055
of N-N bond C022 diazoalkane C064, C106
diazoketone B083 A014, A053, B037, B090, B094, B124
diazomethane B010, B024, B059, B122 α-
diazonium salt A037, B013, B065, B081, A061, B049, B075, C021, C064, C089, C096
B082 β-
Dieckmann condensation A021 A073, A075, B060, B128, C021, C024, C061,
Diels-Alder reaction A064, B027 C084, C109
aza C056 β-carbon C087
hetero enamide C029
B120, B125, C018, C035, C044, C048, C091 enamine
intramolecular A022, B008, B046, B047, B054, B112, C022
B025, B027, B028, C005, C013, C040, C044, endoperoxide B034, B035, C079
C084 ene reaction A067, A068
inverse electron demand B088, C091 Magnesium- C085
retro A064, B027, B088, C044, C064 oxy- B121, C032
dienone-phenol rearrangement A048 enol A013, A024, A025, A032
1, 3-dipolar cycloaddition enol ester A027
C022, C031, C079, C091 enol ether
intramolecular A010, A039, A063, C024, C025
B029, B096, C023, C098 enol lactone B099
of azomethine ylide B096 enolate
of carbonyl ylide C015 A018, A019, A020, A021, A023, A060, C019
of diazomethane B122 episelenide B102
of nitrile oxide B089, B090 episulfide B044
of nitrone A065, B029, C098, C103 episulfone B122
of ozone A029, Bl16, Bll7, C049, C050 episulfonium salt C100
diradical C021, C038, C080 epoxidation C013, C109
divinylcyclopropane rearrangement epoxide
C042, C093 A056, B003, B004, B023, B040, B045, B058,
double inversion B081 B104, C076, C089, C096
E1 elimination B019 Eschenmoser fragmentation B004
E2 elimination B044, B049, B104 Eschweiler-Clarke methylation A053
electrocyclic reaction ester A001, A002, A007
2e B076, C107 esterification A002, A007
4e A066, B025, B026, C008. C054
6e F~H
B087, B106, B126, B127, C008, Favorskii rearrangement A060, B057
C041, C054, C057, C101, C104, C107 Ferrier rearrangement C025
8e C057 Fischer carbene complex B127, C069, C093
elimination Fischer indole synthesis B031, B082
syn- fragmentation
 B004, B070, B 103, C046, C076 hypobromite B038
Friedel-Crafls acylation A036, C059
Gabriel synthesis A052 I~K
Gilbert reagent B036 imide B113
Grignard reagent A004, A005, A006, iminium ion A005,A011, A012, A013, A018,
A016, A074,C066, C085 A033. A053, B046, B047, B078, B114, C007
Grob fragmentation B016, B086, C027, iminophosphorane B100
C044, C094 indole B031, B047, C038. C066
group transfer reaction B074 insertion
Heck reaction A075 of carben A059, A061, C054. C064
Hell-Volhard-Zelinsky reaction A025 of carbon monoxide
hemiacetal C001, C076 B042, B127. C069
hemiaminal A005, A011, B001 of carbonyl group C026
Hofmann rearrangement A057 intramolecular carbopalladation
Hofmann-Lrffler-Freytag reaction B033 C061, C087, C 109
Horner-Wadsworth-Emmons reaction inversion A045, B040. B109
A071, B036, B099 iodination A026. B084
Hosomi-Sakurai-type reaction C053, C062 iodoform reaction A026
hydrazone ipso-substitution C009
A017, B003, B004, B031, B050, B082, C006 isocyanate A057, A058
hydride abstraction B068 isocyanide B048, B065. B118,. C007
hydride shift A077 Jones oxidation A068
hydride transfer ketene A059, A066, C052, C067
A053, B002, B052, C026, C030
hydroboration A028, B086, C030 L~N
hydroformylation B042 lactam A055
hydrogen shift lactol C013, C079
1, 5- B027, B030 lactone A054. B058
1,9- C101 macrocyclic B111
hydrogenation B043 α- B114
hydrolysis β- C045
of acid chloride A025 lactonization B066, B115
of azlactone A019, C009 bromo- C097
of borate A028 iodo- B058
of ester A001, A023 seleno- B124
of N-methyl-N-nitrosulfonamide B024 leaving group A002, A017, A058
of nitrile A011 Leimgruber-Batcho indole synthesis B047
hydrometallation B042, B043 lone pair A001, A002
hydropalladatio C109 malonate A018, A023, A040
hydroperoxide C094 Mannich reaction
 A013, B001, B092, B111, C071, C091 oxazoline B048
Masamune-Bergman cyclization C011 oxidation
Meerwein arylation B013 of alcohol A042, A043, B014
Meerwein-Ponndorf-Verley reduction of palladium (0) A077
B002, C031 oxidative addition
Meisenheimer complex B022. C002 A076, B042, B043, C061, A075, B105, C010
mercury(II) triflate A032. B108 oxime
metathesis A014, A015, A055, B070,
alkene A078, B 109, C034, C093 B089, B120, C014, C098
alkyne B109, B127, C034, C093 oxonium ion A002, C036
enyne B109, C034 oxymercuration A031, A032, C025
Michael addition oxypalladation A077
B004, B005, B006, B008, B053, B054, ozonide A029
B066, B070, B123, C098, C104 ozonolysis
migration A029, B116, B117, C049, C083, C094
A028, A055, A057, C075, C099, C102, C109
Mitsunobu reaction A045, B079, C065 P
mixed anhydride palladacycle C087
A003, A019, A058, B007, B060, palladium-mediated reaction
B061, C012, C023., C051, C104 A075, A076, A077, C010,
Morita-Baylis-Hillman reaction B053 C060, C061, C087, C109
Mukaiyama aldol reaction C102 partial reduction C051, C057
Nazarov reaction B026, C003, C039 Perkin reaction B007
Neber rearrangement B056 peroxide A054, A056, B018
nitrene B080, C038 Peterson olefination A074, C016, C051
nitrile A005, A014, A015, B062, B064 Pfitzner-Moffatt oxidation B014
nitrile oxide B089, B090, B120 phenonium ion B084, B111
nitrilium ion A011, A034, A049, B065 phosphinite ester C082
nitrite B097, C014 phosphonate A070, A071
nitrone A065, B029, C078, C098, C103 photo-cleavable protecting group B098
Norrish type I reaction C080 photo-induced homolytic cleavage
Norrish type II reaction B125 B072, B074, C014
N-oxide A053, B062 photoreaction
B032, B033, B097, B125,
O C014, C041, C080, C105
organochromium species B041 Pictet-Spengler reaction A033, B051
organosamarium species B107 pinacol rearrangement A047, C088
orthoester B084, B091, C070 protodesilylation C005, C023
orthoformate A009 proton transfer
oxa-di-π-methane rearrangement C105 A008, A009, A011, A012, A013, A014
protonation Robinson annulation B008
A001, A002, A005, A006, A008, Robinson-Schöpf reaction B001
A009, A011, A054, A063 ruthenium carbene complex
Pummerer rearrangement B037 A078, B109, C034
pyrylium ion C079
S
Q~R samarium(II) iodide
o-quinodimethane A066, B025 B107, C015, C043, C100
aza- B030 Schmidt reaction B111
quinone C082 selenimn dioxide A068
o-quinone monoacetal C040 selenoxide A073, B124, C024
o-quinonemethide C035 Shapiro reaction B050
p-quinonemethide B063 [2, 3] sigmatropic rearrangement
radical A068, B095, B106,
A031, A050, A051, B013, B017, B018, B032, C033, C037, C047, C048, C092
B033, B038, B039, B071, B072, B073, B097, [3, 3] sigmatropic rearrangement
B107, Bl18, C011, C028, C043, C052, C063 A062, A063, B031, B091, B093,
radical addition C028, C106 C047, C058, C066, C068, C071, C075, C078
radical anion A038, A039, B069, B073 silametallation B105
radical chain reaction silicate ion B105
A050, A051, B013, B017, B018, silyl enol ether C049
B032, B033, B038, B071, B072, single electron reduction B041
B073, B074, B 118, C028, C(163 single electron transfer
radical cyclization B107, C011 A038, A039, B011, B013,
5-exo-dig B017, C043 B073, B107, Bl15, C015, C043
5-exo-trig singlet oxygen B034, B035, C079
B017, B071, B074, BllS, C011, C043, C052 Smiles rearrangement C002
transannular B018 SN 2 reaction
Ramberg-Bäcklund reaction B072, B122 A041, A052, A070, A072, B010, B019,
RCM (ring closing metathesis) A078 B020, B059, B104, C023, C063, C082, C100
reductive elimination intramolecular
A075, A076, B042, B043, B105, B045, B101, B102, Bl10, C001
B127, B128, C010, C087, C093 SN 2' reaction B035, C085
Reimer-Tiemann reaction A035 SRM reaction B073
retro-Cope elimination C072 Staudinger reaction B101
rhodium carbene complex Stetter reaction B006
B126, C015, C074, C075 Stobbe condensation B009
ring contraction B111, B 115 Stork enamine reaction A022
ring expansion B024, B054, C109 Strecker amino acid synthesis A011
Ritter reaction A049 sulfenate C033
sulfene B122 Wittig reaction A069, B080
sulfinate ion B048, B050, B079 intramolecular B100, B123, C086
sulfinic acid C065 [1, 2] Wittig rearrangement B069
sulfonation B085 [2, 31 Wittig rearrangement C077
sulfoxide B037, C033 Wolff rearrangement A059, C054
Suzuki-Miyaura coupling A076 Wolff-Kishner reduction A017
Swern oxidation A043, C097 xanthate A051, C089
ylide B103, C050
T~Y azonmthine B096
Tamao oxidation B105 carbonyl C015, C079
Tamao-Fleming oxidation C005 phosphorus
tautomerization A069, B100, B123, C019, C086
A011, A013, A023, A032, A066 sulfur
thiazolinium ion B006 A043, B014, B095, B 110, C037, C099
thioacetal B095 ynolate C045, C054
thioaldehyde B125
thionocarbonate B103
thiophile C048
thiourea A072
Tiffeneau-Demjanov-type rearrangement
B024, C022
Tishchenko reaction C026
titanacyclopropane B128, C020
TosMIC (p-toluensulfonylmethyl isocyanide)
B018
transmetallation A076
trimethylenemethane diradical Cl06
Ugi reaction C007, C084
Vilsmeier reaction A012
vinylcyclobutane-cyclohexene rearrangement
C088
vinylcyclopropane rearrangement C021
vinylogous amide A022
vinylphosphonium salt B100
vinylsulfonium salt B110
Wacker oxidation A077
Wagner-Meerwein rearrangement
A046, B023, B085, C095, C097
Wharton rearrangement B003
Wilkinson complex B043, C076