近日，东北师范大学毕锡和团队报道了铑催化动力学拆分合成立体选择性多取代双环[1.1.0]丁烷。相关论文于2026年9月8日发表在《科学》杂志上。

双环[1.1.0]丁烷（BCBs）是一类独特的张力小环碳环，在合成化学和药物化学中日益重要。然而，多取代BCBs的对映选择性合成在很大程度上仍是一个尚未解决的挑战。

研究组报道了一个通用化学平台，可分别通过分步[2+1+1′]或一锅[2+1+1]环加成反应，从内炔烃和卡宾出发，立体选择性组装手性或内消旋1,2,3,4-四取代BCBs。这些转化的成功实施得益于三氟甲磺酰腙（卡宾前体）与手性二铑催化剂的组合。位阻较大的催化剂Rh₂(R-3,5-diPheTPCP)₄具有受限的手性微环境，能够精细区分环丙烯对映体，并在与手性铑卡宾反应时通过动力学拆分得到高度对映体富集的多取代BCBs。该化学方法在温和反应条件下进行，使用易得的起始原料，并表现出广泛的底物范围。

附：英文原文

Title: Stereoselective polysubstituted bicyclo[1.1.0]butane synthesis by rhodium-catalyzed kinetic resolution

Author: Xiaolong Zhang, Rongkai Wu, Zhaohong Liu, Ge Yin, Jiaqi Tang, Paramasivam Sivaguru, Xin Hong, Edward A. Anderson, Xihe Bi

Issue&Volume: 2026-09-08

Abstract: Bicyclo[1.1.0]butanes (BCBs) are a distinctive class of strained small-ring carbocycles of growing importance in synthetic and medicinal chemistry. However, the enantioselective synthesis of polysubstituted BCBs remains a largely unsolved challenge. Herein, we report a general chemical platform for the stereoselective assembly of chiral or meso 1,2,3,4-tetrasubstituted BCBs from internal alkynes and carbenes via stepwise [2+1+1’] or one-pot [2+1+1] cycloaddition reactions, respectively. Successful execution of these transformations exploits the combination of triftosylhydrazones (carbene precursors) and chiral dirhodium catalysts. The sterically hindered catalyst Rh2(R-3,5-diPheTPCP)4 features a confined chiral microenvironment that enables exquisite discrimination between cyclopropene enantiomers, affording highly enantioenriched polysubstituted BCBs through kinetic resolution upon reaction with chiral rhodium carbenes. This chemistry operates under mild reaction conditions, employs readily available starting materials, and exhibits broad substrate scope.

DOI: 10.1126/science.aeh6251

Source: https://www.science.org/doi/10.1126/science.aeh6251