英国曼彻斯特大学Procter, David J.团队报道了双环[2.1.1]己烷生物异酯的催化烯烃插入方法。相关研究成果发表在2023年2月13日出版的国际学术期刊《自然—化学》。

富含C（sp³）的双环烃支架，例如双环[1.1.1]戊烷，在药物化学和作物科学中作为苯类化合物的饱和生物异构体发挥着越来越重要的作用。取代双环[2.1.1]己烷（BCHs）是取代邻位和间位取代苯的新兴双环烃生物异构体，但很难获得。因此，如果要实现BCHs作为生物异构体的潜力，就需要一条合成BCHs的通用路线。

该文中，研究人员描述了一种广泛适用的催化方法，该方法通过烯烃和双环[1.1.0]丁基（BCB）酮之间的分子间偶联提供取代的BCHs。SmI2催化的工艺适用于广泛的缺电子烯烃和取代的BCB酮，其SmI2负载量低至5mol%，并由密度泛函理论计算支持的自由基中继机制支撑。产品BCH酮已被证明是多用途的合成中间体，通过选择性下游操作和广谱抗菌剂邻苯二甲酰硫基噻唑的饱和烃类似物的快速合成。

附：英文原文

Title: A catalytic alkene insertion approach to bicyclo[2.1.1]hexane bioisosteres

Author: Agasti, Soumitra, Beltran, Frdric, Pye, Emma, Kaltsoyannis, Nikolas, Crisenza, Giacomo E. M., Procter, David J.

Issue&Volume: 2023-02-13

Abstract: C(sp3)-rich bicyclic hydrocarbon scaffolds, as exemplified by bicyclo[1.1.1]pentanes, play an increasingly high-profile role as saturated bioisosteres of benzenoids in medicinal chemistry and crop science. Substituted bicyclo[2.1.1]hexanes (BCHs) are emerging bicyclic hydrocarbon bioisosteres for ortho- and meta-substituted benzenes, but are difficult to access. Therefore, a general synthetic route to BCHs is needed if their potential as bioisosteres is to be realized. Here we describe a broadly applicable catalytic approach that delivers substituted BCHs by intermolecular coupling between olefins and bicyclo[1.1.0]butyl (BCB) ketones. The SmI2–catalysed process works for a wide range of electron-deficient alkenes and substituted BCB ketones, operates with SmI2 loadings as low as 5mol% and is underpinned by a radical relay mechanism that is supported by density functional theory calculations. The product BCH ketones have been shown to be versatile synthetic intermediates through selective downstream manipulation and the expedient synthesis of a saturated hydrocarbon analogue of the broad-spectrum antimicrobial, phthalylsulfathiazole.

DOI: 10.1038/s41557-023-01135-y

Source: https://www.nature.com/articles/s41557-023-01135-y