Lactic acid derived aziridinyl alcohols as highly effective catalysts for asymmetric additions of an organozinc species to aldehydes

Abstract

A straightforward synthetic route to a series of new catalysts bearing secondary hydroxyl and aziridine moieties as nucleophilic centers built on the chiral skeleton of (S)-(+)-lactic acid is described. All of the new compounds have been tested in the enantioselective addition of diethyl- and phenylethynylzinc to aryl and alkyl aldehydes, yielding the corresponding chiral alcohols in high chemical yields (up to 85%) and good ee’s of approximately 85%. The influence of the stereogenic center located at the aziridine subunit on the stereochemical outcome is also discussed.

Introduction

Asymmetric synthesis is a very important field of synthetic organic chemistry. The broad utility of chiral molecules as single-enantiomer pharmaceuticals, in electronic and optical devices and as probes of biological function has made asymmetric catalysis a prominent area of investigation.¹ In the search for new enantiomerically pure ligands, hydroxy acids constituting a so-called chiral pool are of great synthetic value.² As a result, commercially available (S)-(+)-lactic acid seems to be a potentially attractive chiral platform despite the fact that there are relatively few reports that describe its application in asymmetric synthesis. On the other hand, the enantioselective addition of organozinc reagents to carbonyl compounds is a milestone for the development of novel chiral amino alcohols as ligands³ and, moreover, is one of the simplest methods for the synthesis of chiral non-racemic compounds.4, 5, 6, 7 Recently, we described the synthesis of a series of enantiomerically pure aziridine alcohols derived from (S)-(+)-mandelic acid, and their excellent catalytic properties for the asymmetric addition of diethylzinc and phenylethynylzinc to various aliphatic and aromatic aldehydes.⁸ An easy access to both enantiomers of the products using isomeric forms of the catalysts was reported as well. In a continuation of our current interests in the field of asymmetric synthesis,9, 10, 11, 12, 13, 14, 15, 16, 17 we decided to synthesize a series of new chiral catalysts exploiting (S)-(+)-lactic acid as a key building block, and check their catalytic activity in the addition of diethyl- and phenylethynylzinc to various aldehydes.