Chiral Lewis Base Catalyzed Aldol Reaction of Unprotected Carboxylic Acids

Key words

aldol reaction - phosphine oxides - Lewis base catalysis - carboxylic acids

Significance

Nakajima and co-workers report the first example of a chiral Lewis base-catalyzed ­SiCl₄-mediated enantioselective aldol reaction of unprotected carboxylic acids. The method is highly enantio- and diastereoselective, and it shows a broad substrate scope.

Comment

Previous works on asymmetric aldol reactions of unprotected carboxylic acids by various groups (see, for example: K. Yu et al. J. Am. Chem. Soc. 2017, 139, 527) required stoichiometric chiral reagents to achieve enantioselectivity, but in the presented method, the authors use SiCl₄ to activate the carboxylic acid, permitting the use of only a catalytic amount of a chiral Lewis base to achieve high enantioselectivity.