Synthesis of alkenyl boronates through stereoselective vinylene homologation of organoboronates

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 trans 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 S_N2- and S_N1-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 cis-selective vinylene homologation.