Highly Diastereoselective Chelation-Controlled Additions to alpha-Silyloxy Ketones

The polar Felkin-Anh, Cornforth-Evans, and Cram-chelation models predict that the addition of organometallic reagents to silyl-protected a-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 a-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 alpha-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.