The formyl C–H⋯O hydrogen bond as a critical factor in enantioselective Lewis-acid catalyzed reactions of aldehydes

Abstract

X-Ray crystallographic studies have provided experimental evidence for the existence of intramolecular formyl C–H hydrogen bonds to oxygen or fluorine ligands in complexes of aldehydes and boron Lewis acids. This type of hydrogen bond can be regarded as ‘induced’ or ‘cooperative’ in the sense that its strength can be expected to increase as the bonding between the formyl oxygen and the Lewis acid becomes stronger. Coplanarity of the formyl group and the metal–X subunit to which it is bound in a five-membered ring effectively restricts rotation about the donor–acceptor bond between the formyl oxygen and the metal center of the Lewis acid, thus creating an additional organizing element in these complexes. This organizing element provides a simple and logical basis for understanding the mechanistic basis for enantioselectivity in many reactions of achiral aldehydes which are catalyzed by chiral Lewis acids. These reactions include aldol, allylation and ene addition to the formyl CO group and Diels–Alder reactions of α,β-unsaturated aldehydes with 1,3-dienes. The idea of the induced formyl C–H hydrogen bond can serve as a guide in the design of new enantioselective catalysts as well as a mechanistic principle for understanding preferred transition state assemblies.