Acyclic Stereoselection. 23. Lactaldehyde Enolate Equivalents

Abstract

A number of lactate esters have been synthesized and stereochemistry of the reactions of their enolates with aldehydes examined. Dioxolanones 3 and 4 and oxazolanone 10 show low stereoselectivity (Table I). Methyl esters of various O-alkylated lactic acids (17–19) show generally higher stereoselectivity (Table II). Of these reagents, the best is methyl 2-methoxypropanoate (17), which shows exceedingly high selectivity with aliphatic aldehydes that are branched at C-2. For example, it gives a single adduct with isobutyraldehyde and pivalaldehyde and shows comparable simple diastereoselectivity with the chiral aldehydes 29 and 30. Hindered aryl esters of O-benzyllactic acid (37–39) show complex behavior (Table III), with the sense and magnitude of stereoselectivity clearly being associated with the steric bulk of the aryl group (Table IV). The most useful member of this series of compounds is 2,6-di-teH-butyl-4-methylphenyl (butylated hydroxytoluene, BHT) O-benzyllactate (39), which gives only one isomer in its reactions with isobutyraldehyde and benzaldehyde. Ester 39 also shows useful stereoselectivity with chiral, β,γ-unsaturated aldehydes (73 and 76). The stereoselectivities observed in this study may be understood in terms of the transition-state models presented in Figure 2. It is argued on the basis of circumstantial evidence that the lactate esters give enolates of the Z configuration (eq 8 and 15). As shown in Figure 2, it is proposed that the dihedral angle between the carbonyl and enolate double bonds is approximately 90° and that the two stereoisomers in each case arise from transition states A and B. When the R″ group is small (methyl), then transition state A is preferred, leading to the sense of stereoselectivity shown by esters 17–19. However, when R″ is large (BHT), transition state B predominates. The DMP and DIPP esters show intermediate behavior. The studies reported in this paper are the first that demonstrate aldol stereoselectivity with fully substituted enolates. © 1984, American Chemical Society. All rights reserved.