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Organocatalytic Intramolecular [4+2] Cycloaddition between In Situ Generated Vinylidene ortho ‐Quinone Methides and Benzofurans
Author(s) -
Wu Xiaoyan,
Xue Lu,
Li Dongmei,
Jia Shiqi,
Ao Jun,
Deng Jun,
Yan Hailong
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201707523
Subject(s) - cycloaddition , quinone methide , chemistry , intramolecular force , enantioselective synthesis , quinone , organocatalysis , catalysis , organic chemistry , stereochemistry , combinatorial chemistry , medicinal chemistry
Described herein is the enantioselective construction of oxygen‐containing [5‐6‐5] tricyclic heterocycles by an organocatalyzed asymmetric [4+2] cycloaddition of vinylidene ortho ‐quinone methides and benzofurans. According to this methodology, a series of oxygen‐containing [5‐6‐5] tricyclic heterocycles with various functional groups were synthesized in excellent enantio‐ and diastereoselectivities (>99 % ee , >20:1 d.r.). Furthermore, the deuterium‐labeling experiments and high‐resolution mass spectroscopy demonstrated that a vinylidene ortho ‐quinone methide intermediate was involved and possibly resulted from a prototropic rearrangement of 2‐ethynylphenol. Remarkably, a catalyst loading as low as 0.1 mol %, and a gram‐scale synthesis were achieved for this transformation.