美国得克萨斯大学西南医学中心Qin, Tian团队报道了烷基生物异构体分子内偶联合成多取代双环烷基硼酸酯。相关研究成果于2021年9月28日发表在《自然—化学》。

在医药、农药和材料化学中，双环烃，特别是双环[1.1.1]戊烷（BCPs），作为饱和生物异构体发挥着新兴的作用。利用应变释放策略，以前的合成研究以[1.1.1]推进剂合成桥头取代（C1，C3）BCP为特征。

该文中，研究人员描述了一种通过分子内环化获得多取代BCP的方法。除了C1，C3二取代BCP外，该方法还可以从容易获得的环丁酮中构建未充分开发的多取代（C1，C2和C3）BCP。通过合成多种其他笼状双环分子（范围从[2.1.1]到[3.2.1]支架），验证了该方法的广泛通用性。环化反应过程中产生的悬垂桥头硼频哪醇酯所提供的模块化已通过几个下游功能化得到证明，同时突出了该方法能够实现多取代双环烃的程序化和发散合成的能力。

附：英文原文

Title: An intramolecular coupling approach to alkyl bioisosteres for the synthesis of multisubstituted bicycloalkyl boronates

Author: Yang, Yangyang, Tsien, Jet, Hughes, Jonathan M. E., Peters, Byron K., Merchant, Rohan R., Qin, Tian

Issue&Volume: 2021-09-28

Abstract: Bicyclic hydrocarbons, and bicyclo[1.1.1]pentanes (BCPs) in particular, are playing an emerging role as saturated bioisosteres in pharmaceutical, agrochemical and materials chemistry. Taking advantage of strain-release strategies, prior synthetic studies have featured the synthesis of bridgehead-substituted (C1, C3) BCPs from [1.1.1]propellane. Here, we describe an approach to access multisubstituted BCPs via intramolecular cyclization. In addition to C1,C3-disubstituted BCPs, this method also enables the construction of underexplored multisubstituted (C1, C2 and C3) BCPs from readily accessible cyclobutanones. The broad generality of this method has also been examined through the synthesis of a variety of other caged bicyclic molecules, ranging from [2.1.1] to [3.2.1] scaffolds. The modularity afforded by the pendant bridgehead boron pinacol esters generated during the cyclization reaction has been demonstrated through several downstream functionalizations, highlighting the ability of this approach to enable the programmed and divergent synthesis of multisubstituted bicyclic hydrocarbons.

DOI: 10.1038/s41557-021-00786-z

Source: https://www.nature.com/articles/s41557-021-00786-z