Department of Chemistry, North Carolina State University, 2620 Yarbrough Drive, Raleigh, North Carolina 27695, United States.
J Am Chem Soc. 2022 Mar 23;144(11):4764-4769. doi: 10.1021/jacs.2c00923. Epub 2022 Mar 14.
Sulfone-substituted bicyclo[1.1.0]butanes and housanes have found widespread application in organic synthesis due to their bench stability and high reactivity in strain-releasing processes in the presence of nucleophiles or radical species. Despite their increasing utility, their preparation typically requires multiple steps in low overall yield. In this work, we report an expedient and general one-pot procedure for the synthesis of 1-sulfonylbicyclo[1.1.0]butanes from readily available methyl sulfones and inexpensive epichlorohydrin via the dialkylmagnesium-mediated formation of 3-sulfonylcyclobutanol intermediates. Furthermore, the process was extended to the formation of 1-sulfonylbicyclo[2.1.0]pentane (housane) analogues when 4-chloro-1,2-epoxybutane was used as the electrophile instead of epichlorohydrin. Both procedures could be applied on a gram scale with similar efficiency and are shown to be fully stereospecific in the case of housanes when an enantiopure epoxide was employed, leading to a streamlined access to highly valuable optically active strain-release reagents.
砜取代的双环[1.1.0]丁烷和霍斯烷由于其在存在亲核试剂或自由基物种时在应变释放过程中的板凳稳定性和高反应性而在有机合成中得到了广泛的应用。尽管它们的用途越来越多，但它们的制备通常需要多步反应才能得到低总收率。在这项工作中，我们报告了一种简便通用的一锅法，可从易得的甲基砜和廉价的环氧氯丙烷通过二烷基镁介导的 3-砜基环丁醇中间体的形成来合成 1-砜基双环[1.1.0]丁烷。此外，当使用 4-氯-1,2-环氧丁烷作为亲电试剂而不是环氧氯丙烷时，该过程可以扩展到 1-砜基双环[2.1.0]戊烷（霍斯烷）类似物的形成。这两种方法都可以在克级规模上以相似的效率进行应用，并且在使用手性纯环氧化物的情况下，对于霍斯烷完全具有立体特异性，从而可以简化高价值的光学活性应变释放试剂的获得途径。
