Stereospecific alkenylidene homologation of organoboronates by SNV reaction

• 成果类型: Article
• 署名作者: Chen, Miao; Knox, Christian D.; Madhusudhanan, Mithun C.; Tugwell, Thomas H.; Liu, Coco; Liu, Peng; Dong, Guangbin
• 署名单位: University of Chicago; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh
• 刊物名称: Nature
• ISSN/ISSBN: 0028-5695
• DOI: 10.1038/s41586-024-07579-7
• 发表日期: 2024-07-11
• 页码: 328-+
• 关键词: nucleophilic vinylic substitution; carbon; DYNAMICS; pi; hydroboration; carbenoids; halides; ketones; esters; di

摘要

Concerted nucleophilic substitution, known as S(N)2 reaction, is a fundamental organic transformation used in synthesis to introduce new functional groups and construct carbon-carbon and carbon-heteroatom bonds(1). S(N)2 reactions typically involve backside attack of a nucleophile to the sigma* orbital of a C(sp(3))-X bond (X=halogen or other leaving group), resulting in complete inversion of a stereocentre(2). By contrast, the corresponding stereoinvertive nucleophilic substitution on electronically unbiased sp(2) vinyl electrophiles, namely concerted SNV(sigma) reaction, is much rarer, and so far limited to carefully designed substrates mostly in ring-forming processes(3,4). Here we show that concerted SNV reactions can be accelerated by a proposed strain-release mechanism in metallated complexes, leading to the development of a general and stereospecific alkenylidene homologation of diverse organoboronates. This method enables the iterative incorporation of multiple alkenylidene units, giving cross-conjugated polyenes that are challenging to prepare otherwise. Further application to the synthesis of bioactive compounds containing multi-substituted alkenes is also demonstrated. Computational studies suggest an unusual S(N)2-like concerted pathway promoted by diminishing steric strain in the square planar transition state, which explains the high efficiency and stereoinversive feature of this metallate SNV reaction. We report an SNV reaction, a rare nucleophilic substitution that involves electronically unbiased vinyl electrophiles, which allows the synthesis of cross-conjugated polyenes and bioactive compounds with multi-substituted alkenes.