Enantioselective construction of remote quaternary stereocentres

摘要

四元立构中心（与四个不同碳取代基键合在一起的四个碳原子）是很多天然产物和药物中的一个常见结构主题。这种化合物的对映选择性构造对于合成有机化学家来说仍是一个可怕的挑战。在这篇论文中，作者报告了一种催化和对映选择性分子间Heck-型反应，它能让我们直接获得四元全碳取代的β-、 γ-, δ-、ε-或ζ-芳基羰基化合物。本文所描述的方法是灵活的，允许获得含有一个有丰富对映特性的四元中心的各种不同构造单元。%Small molecules that contain all-carbon quaternary stereocentres-carbon atoms bonded to four distinct carbon substituents-are found in many secondary metabolites and some pharmaceutical agents. The construction of such compounds in an enantioselective fashion remains a long-standing challenge to synthetic organic chemists. In particular, methods for synthesizing quaternary stereocentres that are remote from other functional groups are underdeveloped. Here we report a catalytic and enantioselective intermolecular Heck-type reaction of trisubstituted - alkenyl alcohols with aryl boronic acids. This method provides direct access to quaternary all-carbon-substituted β-, γ-, δ-, ε- or ζ-aryl carbonyl compounds, because the unsaturation of the alkene is relayed to the alcohol, resulting in the formation of a carbonyl group. The scope of the process also includes incorporation of pre-existing stereocentres along the alkyl chain, which links the alkene and the alcohol, in which the stereocentre is preserved. The method described allows access to diverse molecular building blocks containing an enantiomerically enriched quaternary centre.