BCBs~中国农业大学郭红超/周磊杰/张成Org. Lett.:钯催化5-联烯基恶唑烷-2,4-二酮和BCBs的有序分子内环化/[2σ+2π]环加成串联反应
图1. TOC (图片来源于Org. Lett.)Bicyclo[2.1.1]hexanes (BCHs) are important three dimensional bioisosteres of substituted benzenes. Although mono and fused-BCH scaffolds have been extensively studied, spiro-BCH derivatives remain relatively underexplored. Herein, we report a palladium-catalyzed tandem intramolecular annulation/strain-release [2σ + 2π] cycloaddition between 5-allenyloxazolidine-2,4-diones and bicyclo[1.1.0]butanes (BCBs). This method provides efficient and concise access to a novel class of γ-lactam-spiro-BCH scaffolds in moderate to excellent yields. The transformation exhibits broad substrate scope, good scalability, and versatile downstream derivatization of the products.图2. 研究背景及本策略 (图片来源于Org. Lett.)图3. 条件优化 (图片来源于Org. Lett.)图4. 5-联烯基恶唑烷-2,4-二酮底物范围 (图片来源于Org. Lett.)图5. BCBs底物范围 (图片来源于Org. Lett.)图6. 放大反应和转化反应 (图片来源于Org. Lett.)图7. 可能的反应机理 (图片来源于Org. Lett.)In conclusion, we have developed a novel palladium-catalyzed cascade reaction involving intramolecular cyclization and intermolecular strain-release [2σ + 2π] cycloaddition between 5-allenyloxazolidine-2,4-diones and BCBs. This protocol enables the efficient synthesis of a series of novel γ-lactam-spiro-BCH derivatives. The transformation is scalable and the products can be readily diversified. Notably, the method offers excellent step economy by simultaneously constructing both rings of the spiro skeleton in a single operation, which may inspire further designs for the one-step assembly of spiro-bicyclo[n.1.1] frameworks. Current efforts in our laboratory are focused on developing asymmetric versions of this transformation.DOI: https://doi.org/10.1021/acs.orglett.6c01448
