1,2-Addition of Nucleophiles to Carbonyl Compounds - Carbohydrates: Tools for Stereoselective Synthesis - page 286

13

1,2-Addition of Nucleophiles to Carbonyl Compounds
M. Isabel Matheu, Yolanda Díaz, Patricia Marcé and Sergio Castillón

13.1
Introduction

The asymmetric metal-catalyzed addition of different reagents to carbonyl com-
pounds is a useful and efficient procedure for synthesizing chiral secondary and
tertiary alcohols. Similarly, the addition to imines affords chiral amines. Various
catalysts and ligands have been explored for each process, and in some of them
sugar ligands have been tested [1]. In general, the catalytic asymmetric addition
to ketones and ketimines, which gives tertiary alcohols and amines [2], is more
challenging than the addition to aldehydes and aldimines, which gives secondary
alcohols and amines. Many catalytic systems are initially explored for the catalyzed
addition of organometallic compounds to aldehydes and ketimines. Scheme 13.1
summarizes the processes of additions to carbonyl compounds that involve carbo-
hydrate-derived ligands. The most widely studied process is addition of dialkylzinc
reagents to aldehydes (via route a, R 2

H, in Scheme 13.1) [3], which has been
used as a reference for testing new ligands. This process can be catalyzed by

=

OH

OH

R 1 R 3 R 1

R 2

R 2

R 3

R 3 2 Zn

R 3 C CH

[cat] [cat]

a) b)

X=O X=O

X

R 1 R 2

X=O
Me 3 SiCN

X=NR

d)

c)

R 3 C CH

NH 2

HO CN

[cat]

[cat]

R 1 R 2 R 1

R 2

R 3

Scheme 13.1

Carbonyl addition processes involving carbohydrate-derived chiral ligands.