Chemistry Reference
In-Depth Information
2B
ASYMMETRIC ACID - BASE
BIFUNCTIONAL CATALYSIS WITH
ORGANIC MOLECULES
YI WANG AND LI DENG
Department of Chemistry, Brandeis University, Waltham, MA
2B.1. INTRODUCTION
The emergence of asymmetric organocatalysis as a reliable strategy for the develop-
ment of asymmetric reactions represents one of the remarkable advances of synthetic
organic chemistry. Although the chemical mechanisms by which most chiral organo-
catalysts operate, such as enamine catalysis, iminium catalysis, general acid/base catal-
ysis, nucleophilic catalysis, nucleophilic carbene catalysis, and phase-transfer catalysis,
are well known, the spectacularly rapid evolutions of each of these modes of catalysis
since the 1990s establish several new and broadly applicable concepts in catalytic
asymmetric synthesis. Consequently, our view of what small organic molecules could
do as a chiral catalyst has undergone a profound change. This has led to the emer-
gence of enantioselective organocatalysis, a term invented by MacMillian, as a fast-
growing fi eld [1] .
Although acid catalysis and base catalysis, often in cooperation with each other, are
among the most common mechanisms of enzyme-catalyzed reactions [2], literature
reports of highly enantioselective asymmetric reactions based solely on either acid or
base catalysis by organic molecules began to appear only a decade ago. The continuous
progression of asymmetric acid and base catalysis has since then pointed to acid-base
bifunctional organocatalysis as a potentially powerful concept for the development of
effi cient chiral catalysts. However, few, if any, anticipated the progress to be so remark-
able that the studies of acid-base bifunctional organic catalysts would become one of
the most active areas in asymmetric catalysis within 5 years of the fi rst demonstration
of “a proof of principle.” This review aims to capture the key conceptual evolutions and
