Chen Miao, Tugwell Thomas H, Liu Peng, Dong Guangbin
Department of Chemistry, University of Chicago, Chicago, IL, USA.
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.
Nat Synth. 2024 Mar;3:337-346. doi: 10.1038/s44160-023-00461-w. Epub 2024 Jan 3.
Matteson homologation of organoboronates is an attractive approach for constructing aliphatic carbon chains via iterative insertion of carbenoids. However, the corresponding homologation that can introduce alkene moieties to molecular backbones remains elusive. Here we report the development of a stereoselective vinylene homologation reaction of various alkyl and aryl boronates. The reaction proceeds through diastereoselective consecutive insertion of a silyl- and an alkoxy-substituted carbenoid, followed by a Peterson-type elimination. A diverse range of alkenyl boronates can be formed in good yield and with good to excellent selectivity. Density functional theory calculations reveal the origin of diastereoselectivity in carbenoid insertion and how Lewis acids with different sulfide binding affinities affect the competing S2- and S1-type 1,2-boronate migration pathways with distinct levels of stereospecificity. This protocol has been applied to the programmable synthesis of piperamide-family natural products through iterative vinylene and methylene homologations. Guided by mechanistic understanding, the use of oxyphilic Lewis acids has enabled the development of a -selective vinylene homologation.
有机硼酸酯的马特森同系化反应是一种通过类卡宾的迭代插入来构建脂肪族碳链的有吸引力的方法。然而，能够将烯烃部分引入分子主链的相应同系化反应仍然难以实现。在此，我们报道了各种烷基和芳基硼酸酯的立体选择性亚乙烯基同系化反应的开发。该反应通过硅基和烷氧基取代的类卡宾的非对映选择性连续插入，随后进行彼得森型消除反应来进行。可以以良好的产率和良好至优异的选择性形成多种烯基硼酸酯。密度泛函理论计算揭示了类卡宾插入中非对映选择性的起源，以及具有不同硫化物结合亲和力的路易斯酸如何影响具有不同立体特异性水平的竞争性S2-和S1-型1,2-硼酸酯迁移途径。该方法已通过迭代亚乙烯基和亚甲基同系化应用于哌啶酰胺家族天然产物的可编程合成。在机理理解的指导下，亲氧路易斯酸的使用使得能够开发出一种α-选择性亚乙烯基同系化反应。
