Construction of chiral chroman skeletons via catalytic asymmetric [4 + 2] cyclization of ortho-hydroxyphenyl-substituted para-quinone methides catalyzed by a chiral-at-metal rhodium complex

Abstract

An efficient asymmetric [4 + 2] cyclization of α,β-unsaturated 2-acyl imidazoles with ortho-hydroxyphenyl-substituted para-quinone methide derivatives catalyzed by a chiral-at-metal rhodium complex has been developed. Enantioenriched chroman derivatives bearing three contiguous tertiary stereocenters were obtained in generally high yields (up to 97%) and good stereoselectivities (up to >20 : 1 dr, >99% ee). This reaction represents the first catalytic asymmetric [4 + 2] cyclization of ortho-hydroxyphenyl-substituted p-QMs using chiral Lewis acids as catalysts, which will enrich the field of the catalytic asymmetric reactions of p-QM derivatives. More importantly, it also provides a useful method for constructing chiral chroman skeletons.