Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48108-1055, United States.
J Am Chem Soc. 2021 Dec 22;143(50):21234-21240. doi: 10.1021/jacs.1c11170. Epub 2021 Dec 13.
The addition of alkyl fragments to aliphatic aldehydes is a highly desirable transformation for fragment couplings, yet existing methods come with operational challenges related to the basicity and instability of the nucleophilic reagents commonly employed. We report herein that nickel catalysis using a readily available bioxazoline (BiOx) ligand can catalyze the reductive coupling of redox-active esters with aliphatic aldehydes using zinc metal as the reducing agent to deliver silyl-protected secondary alcohols. This protocol is operationally simple, proceeds under mild conditions, and tolerates a variety of functional groups. Initial mechanistic studies suggest a radical chain pathway. Additionally, alkyl tosylates and epoxides are suitable alkyl precursors to this transformation providing a versatile suite of catalytic reactions for the functionalization of aliphatic aldehydes.
向脂肪醛中添加烷基片段是片段偶联中非常理想的转化，但现有的方法在操作上存在与所使用的亲核试剂的碱性和不稳定性相关的挑战。我们在此报告，使用易得的生物恶唑啉（BiOx）配体的镍催化可以催化氧化还原活性酯与脂肪醛的还原偶联，使用锌金属作为还原剂，以提供硅保护的仲醇。该方案操作简单，在温和的条件下进行，并耐受各种官能团。初步的机理研究表明这是一种自由基链途径。此外，烷基对甲苯磺酸盐和环氧化物也是该转化的合适烷基前体，为脂肪醛的官能化提供了一系列多功能催化反应。
