Chiral Primary-Tertiary-Diamine-Bronsted Acid Salt Catalyzed Syn-Selective Cross-Aldol Reaction of Aldehydes

Highly syn-selective cross-aldol reaction of aldehydes has remained a challenging subject in the field of aminocatalysis. To achieve this end, chiral primary amines have been explored and the primary-tertiary diamine-Bronsted acid salts are found to promote the cross-aldol reactions of aldehydes with high activity and syn selectivity. Among various vicinal diamines screened, L-phenylalanine derived 2a/TfOH conjugate is identified as the optimal catalyst, showing good catalytic activity (up to 97% yield) and high syn selectivities (syn/anti up to 24: I, 87% cc). The current catalysis works selectively with small aliphatic aldehydes donors such as propionaldehyde and isobutyraldehyde, but not with aliphatic aldehydes bearing larger beta-substitute (> Me). In addition, the use of 2a/TfOH conjugate has also enabled the first syn-selective cross-aldol reactions of glycoaldehyde donors.