The diastereoselectivity of electrophilic attack on trigonal carbon adjacent to a stereogenic centre: diastereoselective alkylation and protonation of open-chain enolates having a stereogenic centre carrying a silyl group at the β position

Abstract

The alkylation and protonation of enolates having a β-silyl group, prepared by conjugate addition of a silyl-cuprate reagent to enone systems, are almost always highly diastereoselective in the sense 3 in a wide variety of reactions. The effects of varying the type of enolate (Scheme 1) and its geometry, the size of the medium-sized group R¹ on the stereogenic centre (Scheme 3), the nature of the alkylating agent R³X or proton source (Scheme 4), and the size of the substituents R⁴ and R⁵ on the silyl group (Scheme 6) are reported. The stereoselectivity is also high in the creation of some quaternary centres (Scheme 7). Because the phenyldimethylsilyl group can be converted into a hydroxy group with retention of stereochemistry at the β carbon atom, the reaction allows the stereocontrolled synthesis of β-hydroxycarbonyl compounds. The major limitation, as a synthetic method, is that the diastereoselectivity is low, and even occasionally reversed, when the group R³ on the nucleophilic centre is much larger than a methyl group. There is some inconclusive evidence that some of the stereocontrol may be electronic in origin, rather than just steric. Whatever the extent of electronic control, a β-silyl group is an effective control element in electrophilic attack on a double bond, because its electronic and steric effects are likely to operate in the same direction. Neither the kinetic acidity of the esters nor the nucleophilicity of the enolates is noticeably affected by the presence of a β-silyl group.