THE DIASTEREOSELECTIVITY OF ELECTROPHILIC ATTACK ON TRIGONAL CARBON ADJACENT TO A STEREOGENIC CENTER - DIASTEREOSELECTIVE ALKYLATION AND PROTONATION OF OPEN-CHAIN ENOLATES HAVING A STEREOGENIC CENTER CARRYING A SILYL GROUP AT THE BETA POSITION

The alkylation and protonation of enolates having a beta-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 beta carbon atom, the reaction allows the stereocontrolled synthesis of beta-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 beta-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 beta-silyl group.