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有機反応機構
有機反応機構
有機反応機構
大学院入試かち最先端きで
有機合成化学協会 編
化学同人
序 文
学协会の事业の一つとして.有機合成化學協会も以前から便覧や單行本などの出版事
业を行ってきた.しかし,近年出版界を取り卷く事情も大きく変ゎった.そこで,本協
会としこも新かに,時代に即応した出版活動を再出発させょぅということになり,2004
年に出版委員会を新たに立ちあげ,少数の委员で今後の出版企画を検讨してきた.
現代の学问や研究の世界ではおびたガしいほどの研究情報が氾濫しており,それらを
整理し绍介する各种の著作物が数多ぐ出版されている.しかし,ひと昔前に比べて出版
事嶪を取り卷く状况ま大きく変貌している,情報は氾濫しているが.同時にコンピェ一
ェタ技術が著しく発展したお隂で情報処理が簡單になり, とりわけコンビュ一タ検索
により,新しい情報や必要なデ一タの入手が個人レべルでも格段に容易になつた.それ
によつて,今日では出版物の利用侕値が相对的に减少していることは間逹いない.
このような风潮のなかで,有机合成化学協会として出版事嶪を進めるからには,よほ
ど特徴のあるものを指向しなければならない.本協会会員の多くの興味を引を,かつ有
益な情報を提供しうる题目を選びだししかも一般の出版物とは一味逹った,斬新な内容
をもりた企画の提案である.このようなことを念頭において,出版委員会は努力を重ね
ている.
今回第一册目として東京大学大学院薬学系研究科の福山 透教授の研究室で企画编
集された『演习で学ぞ有機反応機構——大学院入試武から最先端まで』を出版すること
になりか.福山研究室では多年にわたり, 有機合成反応を理解し,反応機構を考える力
の飬成のために演習問题を数多く集めてこられた.本書は,それらを系統的にまとめて
编集したもので,般の演習书とはかなり趣きの逹ったユニ一クな内容になっている有機
化学を専攻する学生に有機合成の面自きを会得きせ.また有機合成の研究者にも合成の
实力をアマブさせるために大いに役立つものであり本協会の出版物,としてふさわしし
‘ものキ考えている.
2005 年 7 月
出版委員会委員長
辻 二郎
有機合成化学協会 出版委員会
【出版委員長】 辻 二郎 (東京工嶪大学名誉教授)
【出版副委員長】 竜田邦明 (早稻田大学理工学術院院长)
執 筆 者
福山 透 (東京大学大学院薬学系研究科教授)
德山英利 (東京大学大学院薬学系研究科助教授)
菅 敏幸 (静岡縣立大学薬学部教授)
横島 聡 (東京大学大学院薬学系研究科助手)
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
ま ぇ が き
医薬·农薬の開発から新素材の创製にいたるまで,有机合成化学の重要性は增大の
途をたどっており,それにともなりて新反応や新化合物に関する論文が学術雑誌に氾
濫している.19 世紀以来,連綿と情報を蓄積してきた「有机化学」という厷大な海で,
目指す目的地に逹するためには優れた航海術を身につける必要がある.もちろん,さま
ざまな有機反応を一つ一つ覚ていくのは途方もなく时間がかかるし,非効率的である.
近年,計算化学の発展によって,有機電子論に基づく形式的な反応機構解析の重要さ
が軽視视されるようになった.しかし,電子論を習得することにより,いろいろな反応
を統一的に理解することが可能となり,反応経路の予測や,反応のデザィン,ひいては
合成ル一トの設計に役立つことは明らかである.膨大な既知反応をただ丸暗記するだけ
では何 も新しいことは生まれないが,その底流にとのような(形式的な)電子の流れ
があるかを見きわめることが新しいアィデアの源泉となりうる.有机電子論,いわゆる
Arrow-Pushing Mechanism では, 主として活性反応穜であるアニオン,カチオンやラジ
カルの安定性および生成·開裂する结合のエネルギ一などを考虑に人れながら,全体と
してエネルギ一的に有利な生成物に導くような経路を考える学問である.初学者にとっ
てとくに重要なのは,分子全体に目をくばり,決して省略することなく反応の各ステッ
ブをノ一トに書いて.次に何が起こりうるかを注意深く考察することである.多くの有
機化学教科書では,取録すべき概念や領域があまりにも多いためか,個々の反応につい
ての解説には十分なスペ一スが割かれていないのが实情である.また,基本的な反応か
ら高度な反応までのメカニズムを詳細に解説した演習書も少ない.
アメリカでは多くの大学の有機化学専攻の大学院生は Cumulative Examination とい
うテストを每月受験し,一定の合格数に逹しなければ博士号の取得早資格が得られな
い.
試験には有機反応機構の問题が多く出题されるので,彼らは自主 にでも有機電子論
を勉强せざるをえない仕組みになっている.一方,わが国では学部や大学院での専門教
育が,アメリカの大学ほど厳しくは求められておらず,所属研究室に学生教育の大半の
责任が委ねられている.てのような現状のもとで有機化学の力をつけるためには,講義
ノ一ト,教科書,それに参考書も学习しつつ,演習书を自習していろいろな重要な反応
の理解を徹底的に自分のものにするのが早道であると信ずる,
本書は初级問題(A),中级問題(B),上级問題(C)と解答编から構成されている《それ
ぞれ A は基礎的で重要な反応问题,B は大学院人試レべルか,それよりやや难易度の高
い問題 c は大学院から実社会の研究者レルの問题が集められている.
初学者は初级编の各問題が完全に自分のものになるまで何度も挑戦すべきであるし.简
單なステッブを省略する癖のついた上级者には初级编も参考になると思う.また,20 分
考えてもわからないときにはさりさと降参して答えを見たほうがょいし,ゎからなかっ
た問題は後目再挑戦して自分のものにすれぱ よい.そのために各問題 には三段阶のチ
ュッソクボックスが用意されている.解答欄に書かれた反応機構は引用文献の著者が提
示したものもあれぼ, 福山研究室で考えたものもあり,両方併记の場合もある,
一般的に,有機反応では不安定な中間体の存在が確認できず,反応経路がブラックボ
ックスのなかに人っていることが多い.したがって,真の反応機構は何かど悩むより
も.論理的に反応機構を考えられるようになることのほうが重要である.本書 の问题
をすべて自分のものにすることができたなら.相当に有機化学の実力がつくことは疑い
ない.なお.解答欄のコメントは短い英語で書かれているが.初学者でもこの程度の英
語ならさして負担 ならないことと,英語のほ うが簡滐に説明できるからということで
ご-i 承願いたい.
本考に劫載された問题の大部分は,当研究室のグル一プミ一ティングで出題された
り,スタッフが選んだものであるが,文部科学省特定領域研究「生体機能分子の創制」
の計画班班員の方がたからご提供いただいた問题も合まれている.ここに感谢した
い.また,本書は前々頁に示す当研究室のスタッフや院生が忙しい 究の合間をぬって
执筆したものであるが,横岛聡助手の献身的な努力なくしては完成しなかったことを特
記 しておきたい.
最後に,本書の企画·製作にご助力いただいた化学同人编集部平 佑幸氏に深く感谢
したい.
2005 年 7 月 東京大学大学院薬学系所研究科
天然物合成化学排究室 福山 透
目 次
● 序文
● 出版委員会一覧ぉょび執筆者一覧
● まぇがき
● 略語表
問 题
■ 初级編
初级編ほ,有機化学の教科書で取ぇぁばちにていゐ基本的な反応中心に構成されていゑ
【例 題】2
問题数 78 題
■ 中级編
中级編ほ,大学院入試かゐ大学院修士課程のレバルた想定して構成ちぉていゐ
【例 題】20
問题数 128 題
■ 上级編
上级編ほ,歴史に有名な反応かち最新の論文まこ,手でたぇ十分な問題かち構成まれていゐ
【例 題】48
問题数 109 題
解 答
解答 初级編
解答 中级編
解答 上级編
【コラム】福山研のグル一プミ一ティング風景
問题き解くコッ
【付 録】有機反応の反応機構を考ぇゐにって
電気隂性度と酸性度定数
【索 引】和文索引ぉょび欧文索引
略 語 表
初级编は.有機化学の教科書で取りあげられている反応を中
心に構成されている初学者は.教科書とともに.一問ずつ矢
印を自らの手で描くことによって,有機反応の考え方の基礎
を学んでほしいまた上级者にとっては,一見簡單そうに思え
る問題が多いかもしれないが,水素原子,電子などの細かな
ところまで一つ一つ丁寜に書いてみると,理解が不十分だっ
た箇所が浮きぼりになると思うより難しい問题を解く前の
凖備運動として取り組んでほしい
例 题 Provide reasonable arrow-push mechanisms for following recations
O O
NaCN (cat)
H
EtOH-H2O
reflux OH
解 答
benzoin condensation
O
H
H
O O
CN CN
O
H
O OH
CN
CN
OH
H
CN
O O
OH
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
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
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
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
福山研究室では周に 1 回.グル一 反応機構が详しく議論されていな
◆コラム①◆
プミ一ティングの時間を使って反 い場合や.論文に记されている反応
応機構の問题演習を行っている問 機構とは别の可能性が考えられる
题演習は,自分の頭で考え実际に手 問题もあるその時は.先生を含め全
を動かして書くことになるので学 員で議論する必ずしも一つの答え
生のトレ*二ングとして非常に効 に絞られるわけではないが,さまざ
果的であり,国内外の有機化学の研 まな可能性を考えることが勉強に
究室で実施しているところも少な なる
福山研のグル一プ
くない参考までに当研究室での問 問題はおもに学生が順番で出題
题演習の樣子を紹介したい. することになっている.慣れない学
まず問題は前の週にあらかじめ 生は*つの問题を探すのに.出題の
配られるこれを一週問かけて自力 数週間前から大騒ぎである図書館
で解いてくるもちろん,分からない で論文の山と格闘することになる
反応剤などについては参考書で調 が.せっかくよい问題が見つかった
ミ一ティング風景
べてもよいことにしているが学生 と思って先軰に見せても.にの問题
同士相談しないのが原則であるた はすでにだされた」にれでは問题に
まに出題ミスが発覚するが.その場 ならない」など厳しい言葉が突きつ
合は速やかに全員に知らせる構造 けられるしかしこのプ D セスがま
式や条件が间違っていれば当然解 た重要な勉強の機会となる问題を
けるはすはなく.考える人の時間を 見つけるためにはまず多くの論文
無駄にするということで.出題は慎 を読まなくてはならすさらに内容
重になされる出題ミス 1 回につき もしっかり理解していはいと.簡單
100 円の罚金を徴収するこの集まっ な「つまらない」問題しか見つける
た お 金 は 忘 年会 の と きの 酒 代 に ことができない慣れてくると.普段
し.一年を振り返る から論文をよく読み,その段階でい
セミナ一当日一问につき 4 人す くつか問題をストックしておくよ
つが当てられ黑板の前にでて解答 うになるあまり長い間ストックし
を书く意気揚々と書きあげること ておくと别の人に出題されてしま
ができれ.ポよいが,解けなかった い,悲しい目に遭うこともしばし|
場合は黑板の前に立ち尽くすこと ゴであるが
になるそれも修行のうちであるそ 問題の解答は.グル*プミ*ティ
こで奮起し次回のやる気につなげ ング後.担当の学生が清書し.研究
てもらえればよいまたそのような 室に保存しているまたその解答は
経験をした問题ほど.強く記憶に残 问题と一绪に PDF フアイルとし.ホ
るようであるあまりにも解答が進 *ムペ*ジで公開している诸般の
まない場合や全員が思わぬ方向に 事情で更新が遲れることもあるが
進んでいる場合は出題者や上级生 ぜひ参考にしていただきたい.
がヒントをだす 福山研究室 HP アドレス
约 15~20 分で時間切れとしその http://www.f.u-tokyc.ac.jp/-fuk
後,出題者による解説を行う出題者 uyama/index-I.htm
は参考論文をもとに解説するが.
問题 中级編
中级编では.大学院入试から大学院修士课程のレべルを想定
して問題を集めてあるまた反応機構の興味深い人名反応も
数多く取りあげられており,合わせて学んでいってほしい前
半は比較的基本的な问題.後半は発展的な问题を中心とし
て,分野ことにまとめてある.後半は手応えを感じる问題も
あるかもしれないが,有機合成化学の公式として,自在に反
応機構が書けるようにがんばってほしい
例 题 Provide reasonable arrow-push mechanisms for following recations
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
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
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
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
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
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
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
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
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
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
B115
Na (4eq)
CO2Et Me3SiCl (4 eq) OSiMe3
toluene
CO2Et reflux OSiMe3
B116
O3
MeOH-CH2Cl2
-78 oC;
TsOH
-78 oC to rt 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
反応機構の问题を解くにあた 反応機構(矢印)を書いてみること
◆コラム②◆
って付録にも述べたような基礎的 が重要である反応剤が反応機構で
な化学の知識が重要なことはもち 分類されていると.知らない反応剤
ろんであるがそれ以外にもちよっ にでくわしてもその働きを類推す
とした]ツがある ることができるようになる
①構造式をしっかりと書くこと またわからない反応剤について
有機化学は構造式のおかげで比 調べた際には.目的の反応だけでは
較的手軽に.あたかも目の前で起こ な く . で き るだ け 視 野を * く も
っているかのことく纸の上に書き ち.さまざまな使い方を勉强強る癖
問题き解くコッ
下すことが可能な学問であるそこ をつけておくと.日々の実験にもお
で問題を解くにあたっては.ます頭 おいに役立つ
のなかで考えたことをどんどん纸 ③多くの可能性を考えること
に書いてみる実際に構造を目にす 実际の反応機構は單純な一本道
ることで次の一手が見えてくるも ではなくある分岐点ではいくつも
のであるまた.構造はできるだけ丁 の可能性が考えられるさまざまな
寜に書くべきである分子が大きく 局面でいかに多くの可能性を考え
なってくると構造式を省略して書 られるかが*つの実力でありまた
きがちであるが. 実際の合成では その多くの選択肢に对しどのよう
分子全体を考えて反応条件を選択 に優先顺位をつけて反応機構の考
しなければならないので.つねに分 察を進めるかが重要である.分岐点
子全体を見るトレ一ニングにもな での判断が不適切であるとわかっ
る. た場合.そこに戻り次の可能性から
中间体に関しても一つすつ丁寜 考察を進める
に書くことをお薦めする頭のなか の分子の構造を精查すること
で反応機構を進めてしまい.実際に 出発物と生成物のどことどこが
出発物と生成物のみしか書かない 对 応 し て い るか を 分 析す る こ と
習慣が身についてしまうと.少し変 も.問題を解く重要なヒントになる
わった反応が起こるときに.重要な また生成物から条件を逆にたどっ
分岐点となる中間体を見逃してし ていき.中間体を予測するほうが簡
まうまた*つの構造式で多くの矢 單な場合もある
印を書き反応を進めてしまうこと ノシ反応点からの数を数えてみよ
も,同じ理由で危険をはらんでいる う
一つの中間体につき三つの矢印く 問题を解いていて,ふと詰まるこ
らいが適当である. とがあるそんなときは数を数えて
②反応剤を知っておくこと みよう*つの反応点から数えて.五
まったく知らない反応剤が使わ つ目か六つ目の原子に**する反
れている場合,その問題を解くこと *点があれば.そこで分子内反応
は難しいので,反応剤についてはや (分子内関与)が起こることが多い
はりある程度の知識が必要である 当研究室ではそのような問題で困
しかし辞書的ににの反応剤を使う っている学生がいると,「まだ幼稚
とコレができる」というように结果 園を卒嶪できないな」といわれてし
だけを覚えるのではなく.ますはそ まう幼稚園生でも数ぐらいは数え
の られると.
問题 上级編
上级编では,歴史的に有名な反応から最新の論文まで,手応
え十分な問題を収載してある,しかしいすれも基本に忠実に
解いていけば,解答に到逹できるものばかりである.問題の
順番は分野に関傒なく完全にランダムに配置してあるが.お
およそ難易度順に配列してある.一つ一つ着実に,くじける
ことなく何度でも挑戦してほしい.
例 题 Provide reasonable arrow-push mechanisms for following recations
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
C001
O MeO OMe
OMs NaOMe OH
Me H MeOH, rt Me H
t-Bu t-Bu
C002
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
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
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
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
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
C053
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
MeCN
Br 130 oC O
O
C062
Me3Si OH
O OH
TsOH EtAlCl2 O
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
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
C088
O Li LiBH(s-Bu)3 Me
SPh HBF4 MeLi, KOEt
Me
THF 0 oC Et2O, rt THF, rt
OH
C089
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
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 初级編
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
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
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
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
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
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
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
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
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
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
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
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
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
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
CF3CO2H NH NH NH
MeO MeO MeO
+H+ B H
I I I
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
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+
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
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
A039
OMe O OMe O OMe O OMe O
H NH2
O O O O
A B H
e H
H NH2 e
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
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
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
O O Me
Me - Ph3P O
O O CO2Et
Ph3P
O CO2Et
Me
Br Me Me Me
B Br C Br
H
A047
H
H H
HO O -H2O
OH A OH OH
-H+
B
OH O
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
Bu3Sn Bu3Sn
S S S
Bu3Sn H
H H
E F
N N
H H
Ph O Ph O
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+
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
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
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
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
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
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
A069
PPh3
O O PPh3 O PPh3 - Ph P O CH2
CH2 3
A B C
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
Na H Na
H
NaH O SiMe3 O SiMe3 -Me3SiO-
B C
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
Me
OH
(HO)2B (HO)3B
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 中级編
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
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
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
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
B009
O O H O
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
B011
OTs
OTs OTs
O
O O
e e
Li/NH3
OTs
workup
+H+
O O O O
H
H A B
Cl Cl
NH2 H
NH2
CN CN
H NH2
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
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
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
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
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
O O
1O Ph3P
O 2 O O
O B Ph3P
O
- Ph3P O O
O
PPh3
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
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
Ar
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
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
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
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
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
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
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
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
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
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
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
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
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
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
H Cl Cl
H
A
Cl O H OH Cl OH
O
N O N O
N
Cl
B C D
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
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
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
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
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
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
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
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
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
MeOH
OMe
-H+ NaHCO3
O
R OMe HO OMe
Me2S
OMe E
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
B118
AIBN
n-Bu3Sn X n-Bu3SnH n-Bu3Sn
A
H
X=Cl or I
OEt OEt
I Snn-Bu3
O O
-n-Bu3SnI
C H
C N C N CN
Me
t-Bu
e
M Me
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
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
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
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
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
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
C006
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
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
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
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
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
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
Cl3C C N
O OH O
DBU
N H MgBr N Cl3CCN N
workup -H +
N N N
Tr Tr A Tr
O N O NH O NH
H OR Ca(OCl)2
N N N H2O
N N N
Tr Tr Tr
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
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
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
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
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
C025
Cl H2O
Hg HgCl
Cl HO HgCl
AcO AcO AcO
O O -H+ O
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
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
RuLn
RuLn RuLn
A
R R
Me Me Me
B
RuLn RuLn Ru
Ln
Me Me Me
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
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 +H+ Me MeOH
Me Me Me
MeOH
OMe
OH2 OH -H+ OH2 -H+ H
C Me
Me Me +H+ Me
Me Me
H
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
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
D +H+
TMS R TMS R
I2SmO HO
Me workup Me
H H
D +H+
H H
O O
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
O
MeO O MeO2C
MeO
H H H
OMe
B OMe C OMe
O O O
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
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
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
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
C056
OBn OBn OBn
H NH3 H HO H H
O HO
HN N
OHC H
OH OH
H
H H -H+ H
A B
HN HN HN
C057
H2
Lindlar catalyst
A
HO OH
HO OH
H
H OH
B H H C
HO OH HO
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
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
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
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
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
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
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
C089
Boc Boc Boc Boc
N N N N
workup
O O OH
O
A B +H+
H H
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
C092
Me Me Me Me
BF3-Et2O
Me Me Me
H2O OH2 -SO2
BnO BnO BnO
C
S H S
N O O O
BF3
O
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
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
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
C099
TBS TBS TBS
O O O
O O
O HBF4
OH OH OH
A Ph2S B
Ph2S
H H H H H H
H H H H H H
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
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
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
-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
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
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
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
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
有机反応の反応機構 を考えるにあたって
1.反応機構を考えるうえで重要な電気隂性度
有机反応は,その反応樣式によって極性反応,ラジカル反応,ペリ環状反応などに分
類されるが,その多くの部分を占める極性反応においては,反応系中の電子の豊富な部
位と,電子の不足な部位とが引き寄せ合い,結合の生成,切断が繰り返されながら反応
が進行する.そこに介在しているのは電子であり,反応机构を考えるときに,それらの
電子の动きを「曲がった矢印」を用いて表す.
電子は電子の豊富な部位から電子の不足な部位へと移動していく.そこで,どのよう
に電子が動くかを考える*つの手がかりとなるのが電気隂性度である.電気隂性度とは
結合中の電子を引きつける固有の性質の尺度である.その値が大きいほど電子を引きつ
ける力が強い(すなわち電気的に隂性になる).たとえば臭化メチルを考えると,電子は
+
より電気隂性度の大きい臭素原子上に引き寄せられ,炭素は部分的に正に荷電(δ )し,
臭素原子ほ部分的に負に荷電(δ-)することになる.この臭化メチルに*し,ナトリウ
ムエトキシド(NaOEt)を作用させると,負電荷をもっ酸素原子は,部分的な正電荷をも
っ炭素原子に近づき,新たに酸素-炭素结合が生成する.このとき臭化メチルの炭素-
臭素結合は切断され,その結合を形成していた電子对は臭素原子上に移動し,臭化物ィ
オンを生成する.
δ δ+
-
またカルポニル化合物の反応に関しては次のように考えることができる,カルボニル
基はより電気隂性度の大きい酸素原子上に電子が引き寄せられ,炭素が δ ,酸素が δ
+ -
の部分的な電荷をもつ.カルボニル基に*してアルコキシドのような電子を豊富にもつ
求核基は,部分的な正電荷をもつ炭素原子に近づき,新たな結合を生成する.このとき
炭素-酸素三重结合を形成していたて电子は酸素原子上に移动する.一方,カルボニル
+
化合物に对して塩酸のような Brønsted 酸を作用させると,正の電荷をもっプロトン(H )
と,部分的な负電荷をもっ酸素原予の间で结合が生成してカチオンを生じる.このカチ
オンは,炭素-酸素结合が大きく分極しており,求核基に对してより高い反応性をもつ
ようになる.
R' H
O O O O O
+ O R' H
C C C
R R R R R R R R
このように化合物中の官能基の電荷を考え,最も反応性の高い部位どうしを反応させ
ることが,反応機構を考える基本となる.
表①一般的な元素の電気隂性度
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
HA + H2O A- + H3O+
-
酸 HA に对してプロトンの解離した A を,HA の共役塩基とよぶ.このときその酸性
度の目安として,酸解離定数がしばしば用いられる.希薄水溶液において,化合物の酸
解離定数(PKa)は次のように定義される.
A - H3O +
pKa =
- log Ka =
[ HA ]
この定義によると,PK の値が小さいほどその酸性度は高くなる(平衡が右に偏る,
プロトンを放出しやすい).また塩基(B)の场合を考えると,その共役酸(HB+)の pKa
の値が大きいほど,その塩基性度は高くなる(平衡が左に偏る,プロトンを放しにくい).
-
酸(HA),塩基(酸 HB の共役塩基 B )が共存する場合,その平衡定数 Keq は酸,塩
基それぞれの PKa を用いて次のように記述することができる.
HA + B- A- + HB
A [ HB]
−
− log − =
pKeq = pKa ( HA ) − pKa ( HB )
[ HA ] B
O O O O
Keq より,この平衡はほとんど右侧に偏っていることがわかる.化学的な見方をする
と,弱酸であるマロン酸ジエチルは,强塩基であるナトリウムエトキシドにより,ほぼ
完全に脱プロトン化されている,ということになる.
次に下のスキ*ムのような反応を考えてみよう.リチウムジイソプロピルアミド
(LDA)を用いたアルド*ル反応の例である. n-ブチルリチウム(共役酸 n-ブタンの PKa=
50)は,より PKa の小さいジイソプロピルアミン(pKa = 36)のプロトンを引き抜き,
LDA を生成する.続いて LDA はエステルのα位のプロトン(pKa = 24)を引き抜き,エ
ステルのアニオンを生成する.このアニオンをべンズアルデヒドと反*させると,縮合
体を与えるが,生成物の共役酸の PKa はより小さいアルコ*ル(pKa = 17)となってい
る.後処理で酢酸(pKa = 4.8)を加えると,アルコキシドがプロトン化され,生成物と
酢酸アニオンを生じ反応が终 f する.以上のように,PKa の高い试薬から顺次低いもの
へど移り変わることにより,反応が門滑に進行している.
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
MeSO2Cl
Et3N O Nu- O
HO R Me S O R Me S O + Nu R
CH2Cl2
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
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