Bai Zibo, Lansbergen Beatrice, Ritter Tobias
Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, D-45470 Mülheim an der Ruhr, Germany.
J Am Chem Soc. 2023 Dec 6;145(48):25954-25961. doi: 10.1021/jacs.3c10024. Epub 2023 Nov 27.
Herein we present the first method for the synthesis of bicyclo[1.1.1]pentyl (BCP) alkyl ethers from alcohols. The reaction uses BCP-thianthrenium reagents and is catalyzed by a dual copper/photoredox catalyst system. Unlike known alkylations of tertiary alcohols via carbocation intermediates, our Cu-mediated radical process circumvents the labile BCP carbocations. The approach demonstrates a broad tolerance for functional groups when applied to primary, secondary, and even tertiary alcohols. In addition, we highlight the utility of this method in late-stage functionalizations of both natural products and pharmaceuticals as well as in the rapid construction of BCP analogs of known pharmaceuticals that would otherwise be difficult to access.
在此,我们展示了一种由醇类合成双环[1.1.1]戊基(BCP)烷基醚的首个方法。该反应使用BCP-噻蒽鎓试剂,并由双铜/光氧化还原催化剂体系催化。与通过碳正离子中间体进行的叔醇已知烷基化反应不同,我们的铜介导自由基过程规避了不稳定的BCP碳正离子。当应用于伯醇、仲醇甚至叔醇时,该方法对官能团具有广泛的耐受性。此外,我们强调了该方法在天然产物和药物的后期官能化以及快速构建已知药物的BCP类似物(否则难以获得)方面的实用性。