Asymmetric Alkylation of β-Ketoesters

Abstract

Creating quaternary carbon centers in which the absolute stereochemistry can be controlled by alkylation represents a major challenge.β-Ketoesters become interesting substrates because the structural diversity of the substituents permits ready and selective manipulation.Conceptually, catalytic asymmetric alkylations of such substrates are not straightforward. 1Extrapolation of the concept of asymmetric allylic alkylations 2 to induce absolute stereochemistry in a prochiral nucleophile is tenuous, at best, given the known stereochemistry of the process. 3As depicted in Figure 1, the pronucleophile resides very distal to the chiral ligands in the transition state for alkylation.Not surprisingly, the best ee's for alkylation of 2-carboethoxycyclohexanone have been less than 30% 4 although with a β-diketone significantly higher ee's have been obtained. [4][5]][6][7] An imaginative solution to this problem arises in the case of