Part 2 - General principles on asymmetric synthesis

A B

A
R2 R2
C Z C*
R1 R1
Z B

Enantiomers

Z B
R2 R2
C Z C*
R1 R1
A

A B
 General principles on stoichiometric asymmetric synthesis

A B *
* - X
X A A
R2 R2
R2 R2 C* C*
C Z C Z R1 R1
R1 R1 Z B Z B

* *
X X

Major

*
* - X
X Z B
R2 Z B
R2 R2 R2
C Z C* C*
C Z R1
R1 R1 A R1
A
* *
X A B X

*
Minor X : Chiral auxiliary (temporay)
 Note: extension to asymmetric catalysis

Reaction on the
upper face favored

A B
Coordination very important
R2
C Z
R1
organometallic catalyst
or enzyme
A B

Reaction on the down face

disfavored
 Note: Si and Re Faces

1,2 nucleophilic additions

Re face

O
Nu O- Nu-
1 Nu- -
3 O Nu
R 2 H
R * H Si face Re face R * H
attack attack

Si face

Reactions with enolates

Li+ Re face
R'O O-
1 R"-X
R" CO2R' R"-X R'O2C R"
3
R 2 H
R * H R
Si face Re face * H
attack attack

Si face
 1st pathway: chirality on substrate

New chiral
centre
created

Chirality *
on
substrate
 2nd pathway: chirality on reagent

Chirality
on reagent

New chiral centers

created
 3rd pathway: temporary chiral auxiliary

Temporary
chiral
auxiliary

Recycled Auxiliary
 Conclusions and important points

- Asymmetric synthesis is based upon the possibility to perform a reaction

in a preferred (or exclusive) manner, on only one face from the two
faces of a p prochiral system.

- For stoichiometric asymmetric synthesis, three main strategies are used:

- Use of one, or several, asymmetric center (s) on the

starting substrate;
- Use of chiral reagents;
- Use of temporary chiral auxiliaries. Latter methodology
is the most often employed in this area.