高效合成热力学不稳定的双取代环己烷

The Synthesis of Thermodynamically Disfavored Disubstituted Cyclohexanes

环己烷是最常见并且最重要的环状结构单元之一,饱和环状结构可以提高分子的饱和度,有助于改善化合物物化特性和提高分子生物活性,而取代环己烷及其衍生物则由于广泛存在于天然产物和药物分子中受到合成化学家的关注。从构象上看,根据Barton规则,1,2-反式、1,3-顺式、1,4-反式双取代环己烷的两个取代基可同时处于椅式构象的平伏键,热力学稳定,容易合成。

Thermodynamically disfavored disubstituted cyclohexanes are synthesized with excellent kinetic stereocontrol from readily available substituted methylenecyclohexanes based on chain-walking catalysis.Control experiments and theoretical calculations suggest that the initial introduction of bulky boron ester substitution away from the ring is crucial to the high diastereoselectivity.This finding opens a new adventure to the application of chain walking catalysis in organic synthesis and provides a ready access to thermodynamically disfavored but biologically important disubstituted cyclohexanes and the derivatives.