State Key Laboratory of Applied Organic Chemistry (SKLAOC), College of Chemistry and Chemical Engineering, Lanzhou University, 222 South Tianshui Road, Lanzhou 730000, China.
Hoffmann Institute of Advanced Materials, Postdoctoral Innovation Practice Base, Shenzhen Polytechnic, 7098 Liuxian Boulevard, Nanshan District, Shenzhen 518055, China.
J Am Chem Soc. 2020 Sep 30;142(39):16787-16794. doi: 10.1021/jacs.0c07492. Epub 2020 Sep 17.
Deoxygenative radical C-C bond-forming reactions of alcohols are a long-standing challenge in synthetic chemistry, and the current methods rely on multistep procedures. Herein, we report a direct dehydroxylative radical alkylation reaction of tertiary alcohols. This new protocol shows the feasibility of generating tertiary carbon radicals from alcohols and offers an approach for the facile and precise construction of all-carbon quaternary centers. The reaction proceeds with a broad substrate scope of alcohols and activated alkenes. It can tolerate a wide range of electrophilic coupling partners, including allylic carboxylates, aryl and vinyl electrophiles, and primary alkyl chlorides/bromides, making the method complementary to the cross-coupling procedures. The method is highly selective for the alkylation of tertiary alcohols, leaving secondary/primary alcohols (benzyl alcohols included) and phenols intact. The synthetic utility of the method is highlighted by its 10--scale reaction and the late-stage modification of complex molecules. A combination of experiments and density functional theory calculations establishes a plausible mechanism implicating a tertiary carbon radical generated via Ti-catalyzed homolysis of the C-OH bond.
醇的脱氧自由基 C-C 键形成反应是合成化学中长期存在的挑战，目前的方法依赖于多步反应。在此，我们报告了一种醇的直接去羟自由基烷基化反应。该新方法证明了从醇中生成叔碳自由基的可行性，并为容易且精确地构建全碳季碳原子中心提供了一种途径。该反应具有广泛的醇和活化烯烃底物范围。它可以耐受多种亲电偶联试剂，包括烯丙基羧酸酯、芳基和乙烯基亲电试剂以及伯烷基氯/溴，使该方法与交叉偶联程序互补。该方法对叔醇的烷基化具有高度选择性，留下仲/伯醇（包括苄醇）和酚类物质不变。该方法的 10 克规模反应和复杂分子的后期修饰突出了其合成实用性。实验和密度泛函理论计算的结合建立了一个合理的机制，该机制涉及 Ti 催化的 C-OH 键均裂产生的叔碳自由基。
