Highly Diastereoselective Aldol Reactions of Chiral Methyl Ketones

Diastereoselective aldol additions have emerged as one of the most efficient and versatile methods available for preparing a wide range of optically active compounds.l Very high diastereoselectivities have been reported for aldol reactiona involving chiral enolates derived from a-ethylor higher alkyl-substituted ketone derivatives. By contrast, relatively few examples of highly diastereoselective aldol reactions of chiral methyl ketones2P or aldolreactions of methyl ketones with chiral catalysts have been reported.67 Of these, most do not involve methyl ketonesper se but instead utilize chiral acetate equivalents (XC(0)CHa where X is a chiral a ~ x i l i e ~ ~ ) in which the rotamer population around the C-X bond can be controlled by stereoelectronic factors. In general, metal enolates of chiral methyl ketones, especially the lithium enolates, give poor diastereoselectivity, largely because these systems lack any inherent control of the rotamer population around the nonreacting C-C(0) bond.s11 In this paper we report the results of a study on aldol reactions of lithium enolates of a(Nf l dibenzy1amino)alkyl methyl ketones which proceed with exceptionally high diastereoselectivity, presumably due to the unique ability of the dibenzylamino group to