School of Chemistry, University of Bristol, Bristol, UK.
Nat Chem. 2019 Feb;11(2):117-122. doi: 10.1038/s41557-018-0181-x. Epub 2018 Dec 10.
Transition-metal-catalysed cross-coupling reactions, particularly those mediated by palladium, are some of the most broadly used chemical transformations. The fundamental reaction steps of such cross-couplings typically include oxidative addition, transmetallation, carbopalladation of a π-bond and/or reductive elimination. Herein, we describe an unprecedented fundamental reaction step: a C-C σ-bond carbopalladation. Specifically, an aryl palladium(II) complex interacts with a σ-bond of a strained bicyclo[1.1.0]butyl boronate complex to enable addition of the aryl palladium(II) species and an organoboronic ester substituent across a C-C σ-bond. The overall process couples readily available aryl triflates and organoboronic esters across a cyclobutane unit with total diastereocontrol. The pharmaceutically relevant 1,1,3-trisubstituted cyclobutane products are decorated with an array of modular building blocks, including a boronic ester that can be readily derivatized.
过渡金属催化的交叉偶联反应，特别是钯介导的交叉偶联反应，是应用最广泛的化学转化之一。这些交叉偶联反应的基本反应步骤通常包括氧化加成、转金属化、π键的碳钯化和/或还原消除。在此，我们描述了一个前所未有的基本反应步骤：C-C σ键碳钯化。具体来说，芳基钯（II）配合物与张力双环[1.1.0]丁基硼酸酯配合物的 C-C σ键相互作用，使芳基钯（II）物种和有机硼酸酯取代基加成到 C-C σ键上。整个过程可以通过一个环丁烷单元将易得的芳基三氟甲磺酸酯和有机硼酸酯有效偶联，同时具有完全的非对映选择性控制。具有药物相关的 1,1,3-三取代环丁烷产物可以用一系列模块化构建块进行修饰，包括可以容易衍生化的硼酸酯。
