Asymmetric Catalytic [3 + 3] Annulations of Unmodified Morita-Baylis-Hillman Alcohols to Construct Diverse Heterobicyclic [4.3.0] Skeletons

未修饰的 Morita-Baylis-Hillman 醇的不对称催化 [3 + 3] 环化反应构建多种杂双环 [4.3.0] 骨架

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Abstract

Due to the high C-OH bond dissociation energy and unpredictable site selectivity, the direct application of unmodified cyclic MBH alcohols presents significant challenges. Herein, we described a series of highly enantioselective β,β'-site-selective annulations of unmodified cyclic MBH alcohols, which provides a strategy for the asymmetric construction of structurally diverse chiral heterobicyclic [4.3.0] skeletons. Azabicyclic, oxobicyclic, and thiabicyclic [4.3.0] skeletons could be synthesized with excellent stereoselectivities through this general platform. Catalyst rather than substrate-controlled feature renders the reaction minimal sensitivity to substrate properties. Furthermore, the synthetic potential of this method was underscored by facile access to various pharmaceutically active analogues. This synthetic strategy would accelerate access to accomplish diverse transformations of MBH adducts and advance the frontiers of chiral heterocyclic synthesis.

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