Exercise “Organic Chemistry II @ TUM Asia” – Prof. Dr.

Tanja Gulder 1

Exercise 14 - Carbonyl Chemistry: Claisen, aldol type- and 1,4-additions

A - Basic

A-0. Please repeat Chapter 17 and 18 of the lecture and analyze the reaction examples.

A-1. Give the products of these reactions, which all start from cyclohexanone!
OH
HO MeMgBr
A E
pTsOH (cat.)
PhMe, 110°C
HCO2Et
NaBH4 F
B EtONa
EtOH
O O O P+Ph3Br–
MeO P CN
MeO G
C KHMDS
NaH

1. LDA NaOMe (cat.)

D H
2. Br MeOH

A-2. Give the structures of A-G:

O PPh3
NaOH
Br
OMe
PhMe H2O B
80°C A

O
DIBA-H B
O
PhMe
–78°C cyclic C open chain D

E+F P+Ph3 + KOtBu

Br– G

A-3. Eelectron-poor alkenes bearing – (-M) substituents are not readily epoxidized with peracids.
Which alternative syntheses of such epoxides do you know? (Mechanism / name reaction?).

O a) O b) O
+ +
R R OMe R OMe
O
Exercise “Organic Chemistry II @ TUM Asia” – Prof. Dr. Tanja Gulder 2

B – Deepen your understanding

B-1. a) Reaction of pulegone with hydrogen sulfide and base gives a chemical A, which displays a
black-currant type flavor in concentrations of only 0.1–1 ppm. What is the structure of A?
a) H2S (g), KOH (cat.)
pulegone
EtOH
c) MeMgI
+ CuCl O
A (C10H18OS) 73%
b) MeLi
or
C (C11H20O) MeMgI B (C11H20O)

b) Reaction of pulegone with methyl-lithium or -Grignard reagent gives B. Structure of B?

c) In contrast, the same organometallic reagents give another product C, if they are combined with
a copper(I) catalyst (CuCl). What is the structure of the new compound C?

B-2. A sequence of simple carbonyl group reactions is used to synthesize an important drug:
O OH
O NaOEt
+
EtO OEt similar to Claisen
OH condensation C (not isolable) O O
A B
D
O
Michael
Anticoagulant, rank 18 on the list
addition
of most prescribed pharma-
ceuticals in the USA (2012) E
(blod-thinner, prevents post- F
operative thrombosis). base (cat.)

a) What is the structure of intermediate C from the CLAISEN type condensation of A with B?
b) C cannot be isolated under the conditions used, but immediately reacts to 4-hydroxycoumarin (D).
Write a mechanism for that reaction.
c) What is the structure of target F, which is formed in a MICHAEL-addition of D to E?