ASYMMETRIC PHASE-TRANSFER CATALYSIS - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 211

7
ASYMMETRIC PHASE-TRANSFER
CATALYSIS

CHAPTER

SEIJI SHIRAKAWA, SHIN A. MOTEKI, and KEIJI MARUOKA
Department of Chemistry, Kyoto University, Sakyo, Kyoto, Japan

7.1. INTRODUCTION

Phase-transfer catalysis has long been recognized as a versatile method for organic
synthesis in both industry and academia, featuring simple experimental operations,
mild reaction conditions, inexpensive and environmentally benign reagents and
solvents, and the possibility to conduct large-scale preparations in process
chemistry [1]. In particular, during more than the past two decades, asymmetric
phase-transfer catalysis based on the use of structurally well-defined chiral, non-
racemic catalysts has become a topic of great scientific interest, and recent efforts
have resulted in notable achievements, making it feasible to perform various bond
formation reactions under mild phase-transfer-catalyzed conditions [2]. This chapter
focuses on the recent aspects of asymmetric transformations using various types of
chiral phase-transfer catalysts for the synthesis of biologically active compounds.

7.2. ALKYLATION

Although initial studies on asymmetric alkylation of carbonyl compounds by chiral
phase-transfer catalysis has shown only disappointing results, a first efficient chiral
phase-transfer catalyst N -(4-trifluoromethylbenzyl)cinchoninium bromide ( 1a ) was
devised in 1984 by theMerck group for the enantioselective synthesis of (

)-indacrinone
(MK-0197) via asymmetric phase-transfer alkylation (Scheme 7.1) [3].

þ

7.2.1. Asymmetric Synthesis of a -Alkyl a -Amino Acids
After 5 years of groundbreaking work by the Merck group, similar N -benzyl
cinchoninium halide 1b has been successfully utilized by O'Donnell and coworkers
as a chiral phase-transfer catalyst for the asymmetric alkylation of glycine Schiff