CONCERNING THE DIASTEREOFACIAL SELECTIVITY OF THE ALDOL REACTIONS OF ALPHA-METHYL CHIRAL ALDEHYDES AND LITHIUM AND BORON PROPIONATE ENOLATES

The diastereofacial selectivity of the aldol reactions of alpha-methyl chiral aldehydes and propionate and ethyl ketone derived lithium and boron enolates is analyzed from the perspective of a transition state model suggested by Evans in 1982. The dominant stereocontrol element in these reactions, as in the mechanistically related reactions of crotylmetal reagents and alpha-substituted chiral aldehydes (refs 6, 7a), appears to be the minimization of gauche pentane interactions in the competing transition states. Transition structure 35 is viewed as the lowest energy structure in the ''anti-Felkin'' selective aldol reactions of Z(O)-enolates as long as the steric requirements of R are greater than that of the alpha-Me group. Transition state 36 is similarly the lowest energy structure available in the aldol reactions of E(O)-enolates (Felkin selective). The model also reconciles data involving the aldol reactions of Ph(Me)CHCHO (1a) and R2C = CHCH(Me)CHO (1b, 1c) that preferentially provide the 2,3-syn-3,4-syn (''Felkin'') diastereomers 3: the Ph or vinyl substituents are viewed as the smaller of the two alpha-substituents (Me > Ph or vinyl) since they expose a sterically undemanding, flat surface to the incoming nucleophile in the lowest energy transition structures 39 (for 1a) and 41 (for 1b, 1c).