Enantiospecific Synthesis of Alkylboronate Esters Enabled by Carbopalladation of C─C σ-Bond and Novel Tsuji–Trost-Type Allylations

手性硼酸及其衍生物是立体选择性有机合成中非常有价值的组成部分，因为它们可以经历大量的不对称转化。由于硼化学的巨大潜力，我们的目标是开发新的和不同的反应，使我们能够合成新的和有价值的手性硼化合物。Aggarwal小组在锂化硼化和手性硼化合物及天然产物的流水线合成方面取得了显著进展。Aggarwal等人史无前例地通过碳碳化C-C σ-键（使用环应变策略）进行远端交叉偶联反应，为有机硼化学开辟了新的方向。在这方面，开发一种有效的催化金属位移基转化，使C─C σ键在应变较小的衬底上碳层化是非常可取的。同时，利用外消旋α-halo烯丙基硼酯的Tsuji-Trost反应也为合成富含对映体的烷基硼酸酯提供了很大的机会。在本研究中，我们将研究和设计更通用和更少应变的底物来完成催化“连接”交叉偶联，并合成广泛的外消旋α-halo烯丙基硼酯，以实现与不同亲核试剂的Tsuji-Trost反应。我们设想这些转化可以为不对称合成中使用的手性烷基硼酯构建块的构建提供新的机会。

Chiral boronic acids and related derivatives are highly valuable building blocks in stereoselective organic synthesis because of the multitude of asymmetric transformations that they can undergo. Due to the tremendous potential of boron chemistry, our aim here is to develop new and different reactions that enable us to synthesize novel and valuable chiral boron-compounds. Aggarwal group has made remarkable progresses in lithiation-borylation and assembly-line synthesis of chiral boron-compounds and natural products. The unprecedented distal cross-coupling reaction via carbopalladation of C–C σ-bonds (using a ring-strain strategy) by Aggarwal et al. opens up a new direction in organoboron chemistry. In this regard, developing an efficient catalytic metalate-shift-based transformation to enable C─C σ-bond carbopalladation in less strained substrates is highly desirable. Meanwhile, the Tsuji-Trost reaction utilizing a racemic α-halo allyl boronic ester also provides great opportunities for the synthesis of enantioenriched alkyl boronate esters. In this research, we will investigate and design more general and less strained substrates to accomplish catalytic ‘conjunctive’ cross-couplings and synthesize a wide range of racemic α-halo allyl boronic esters to achieve Tsuji-Trost reactions with different nucleophiles. We envision that these transformations can provide new opportunities for the construction of chiral alkyl boronic ester building blocks for use in asymmetric synthesis.