Highly diastereoselective chelation-controlled additions to α-silyloxy ketones

Abstract

The polar Felkin-Anh, Cornforth-Evans, and Cram-chelation models predict that the addition of organometallic reagents to silyl-protected α-hydroxy ketones proceeds via a nonchelation pathway to give anti-diol addition products. This prediction has held true for the vast majority of additions reported in the literature, and few methods for chelation-controlled additions of organometallic reagents to silyl-protected α-hydroxy ketones have been introduced. Herein, we present a general and highly diastereoselective method for the addition of dialkylzincs and (E)-di-, (E)-tri-, and (Z)-disubstituted vinylzinc reagents to α-silyloxy ketones using alkyl zinc halide Lewis acids, RZnX, to give chelation-controlled products (dr ≥18:1). The compatibility of organozinc reagents with other functional groups makes this method potentially very useful in complex molecule synthesis.

Figure 1

Polar Felkin-Anh, Cornforth, and Cram-chelation models for additions to protected α-hydroxy aldehydes and ketones. Recent studies have highlighted the importance of the Cornforth model over the polar Felkin-Anh model.^,

Figure 2

Proposed transition state to rationalize the extremely high diastereoselectivities observed in this study.

Scheme 1

Diastereoselective Addition of Dialkylzinc and Vinylzinc Reagents to α–Silyloxy Aldehydes

Scheme 2

Chelation-Controlled Methyl Addition to α–Silyloxy Ketones by Reetz and Co-workers.

Scheme 3

Synthesis of 1,2-syn Diols via Allene Hydroboration/Allylation by Roush and coworkers

Scheme 4

Proposed Mechanism for the Generation of (Z)-disubstituted Vinylzinc Reagents.

Scheme 5

Diastereoselective (Z)-Vinylation of an α-Silyloxy Ketone