Enantioselective synthesis of 8-membered lactone derivatives via organocatalytic cascade reactions

Abstract

Enantioselectively accessing medium-sized ring compounds with multiple stereocenters is still a formidable task due to the unfavorable entropy effect. We have developed a protocol for the enantioselective synthesis of eight-membered lactone derivatives through an organocatalytic Michael/ketalization/fragmentation cascade utilizing ortho-quinone methides and cyclobutanone carbon esters as starting materials. This reaction can be conducted under mild conditions using a wide range of substrates and it exhibits excellent enantioselectivity.