Transition-metal-catalyzed cycloaddition reactions of strained small-ring compounds are powerful methods for constructing carbo- and heterocyclic structures of medicinal interest. However, the application of this strategy to bicyclo[1.1.0]butanes (BCBs), which are among the most strained carbocycles known, remains underdeveloped. Herein, we report vinylbicyclo[1.1.0]butane (VBCB) as a platform synthon for palladium-catalyzed formal [2σ+2π] cycloaddition reactions with various 2π-components, enabling the synthesis of BCHs, oxa-BCHs, and aza-BCHs under identical reaction conditions. The zwitterionic π-allyl-Pd species generated through the palladium-catalyzed activation of VBCBs is the key to circumventing potential carbene reactivity and serves as a common intermediate for cycloadditions with diverse 2π-systems, including alkenes, aldehydes, ketones, and imines. Notably, by utilizing Pd₂(dba)₃ and an anthracene-derived Trost ligand, a wide array of BCHs bearing two vicinal chiral centers has been prepared in a highly diastereo-, and enantioselective manner. The generality and practicality of this method have been demonstrated by a broad substrate scope, scale-up reactions, and the versatile transformation of multiple functional groups into BCH scaffolds. Preliminary mechanistic studies support the formation of the π-allyl-Pd species.

中文翻译：

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乙烯基双环[1.1.0]丁烷 （VBCB） 与烯烃、羰基化合物和亚胺的两性离子 π-烯丙基-Pd 物质使乙烯基双环 [1.1.0] 丁烷 （VBCB） 的 [2σ+2π] 环加成反应成为可能


应变小环化合物的过渡金属催化的环加成反应是构建具有药用价值的碳环和杂环结构的有力方法。然而，这种策略在双环[1.1.0]丁烷 （BCB） 上的应用仍然不发达，这是已知的最紧张的碳环之一。在此，我们报道了乙烯基双环[1.1.0]丁烷 （VBCB） 作为钯催化的具有各种 2π 组分的正式 [2σ+2π] 环加成反应的平台合成子，能够在相同的反应条件下合成 BCH、oxa-BCHs 和 aza-BCHs。通过钯催化活化 VBCB 生成的两性离子 π-烯丙基-Pd 物质是规避潜在卡宾反应性的关键，并用作与多种 2π 系统（包括烯烃、醛、酮和亚胺）进行环加成反应的常用中间体。值得注意的是，通过利用 Pd₂（dba）₃ 和蒽衍生的 Trost 配体，以高度非对映和对映选择性的方式制备了一系列带有两个邻近手性中心的 BCH。该方法的通用性和实用性已通过广泛的底物范围、放大反应以及多个官能团向 BCH 支架的多功能转化而得到证明。初步机理研究支持 π-烯丙基-Pd 物质的形成。