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

Dong-Sheng Ji,‡Rui Zhang,‡ Xu-Yan Han, Hai-Long Chai, Yucheng Gu, Xiu-Qin Hu and Peng-Fei Xu*

https://doi.org/10.1039/D4QO00148F

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.