syn-Selective Direct Asymmetric Cross-Aldol Reaction

Significance A highly syn -selective asymmetric direct cross-aldol reaction between two different aldehydes has been developed. By employing 5 mol% of the axially chiral amino sulfonamide ( S )- 3 , syn -aldol products 4 resulting from mostly electron-poor acceptor 1 and aliphatic donor aldehydes 2 are obtained in moderate to good yields along with high diastereo- ( syn / anti ratio up to >20:1) and excellent enantioselectivities (er up to 99.5:0.5). The authors rationalize the stereo­chemical outcome with the help of proposed transition states A and B . In contrast to the anti -enamine B , the syn -enamine geometry in A allows for effective hydrogen bonding activation of the acceptor aldehyde by the acidic proton of the triflamide moiety. This favors the reaction to proceed via the syn -enamine intermediate and explains the observed syn selectivity.