Chiral Lewis Base Catalyzed Aldol Reaction of Unprotected Carboxylic Acids
Catalytic Enantioselective Aldol Reaction of Unprotected Carboxylic Acids under Phosphine Oxide Catalysis.
Angew. Chem. Int. Ed. 2018;
14 December 2018 (online)
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.
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.