Asymmetric Cascade Annulation Based on Enantioselective Oxa-Diels–Alder Cycloaddition of in Situ Generated Isochromenyliums by Cooperative Binary Catalysis of Pd(OAc)2 and (S)‑Trip

• Published in: Journal of the American Chemical Society Vol. 135; no. 30; pp. 11402 - 11407
• Main Authors: Yu, Shu-Yan, Zhang, Hao, Gao, Yang, Mo, Lei, Wang, Shaozhong, Yao, Zhu-Jun
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 31.07.2013
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja405764p

An asymmetric cascade annulation between 2-hydroxystyrenes and 2-alkynylbenaldehyes or 1-(2-alkynyl­phenyl)­ketones has been established with good to excellent enantioselectivities (up to >99.5% ee), on the basis of an enantioselective oxa-Diels–Alder cycloaddition of in situ generated metallo-isochromenylium intermediates, by cooperative binary catalysis of Pd(OAc)2 and (S)-Trip. The developed methodology is workable for a broad spectrum of substrates and shows great efficiency in establishing dense multiple chiral centers including quaternary carbons of variable bridged ring systems. The mechanism study suggests that (S)-Trip plays multiple roles in assembling the reactants and controlling the stereoselectivity.