Ye Zhishi, Cai Xinpei, Li Jiawei, Dai Mingji
Department of Chemistry, Center for Cancer Research, and Institute for Drug Discovery, Purdue University, West Lafayette, IN 47907, United States.
ACS Catal. 2018 Jul 6;8(7):5907-5914. doi: 10.1021/acscatal.8b00711. Epub 2018 May 11.
Catalytic ring opening cross coupling reactions of strained cyclopropanols have been useful for the syntheses of various β-substituted carbonyl products. Among these ring opening cross coupling reactions, the formation of α,β-unsaturated enone byproducts often competes with the desired cross coupling processes and has been a challenging synthetic problem to be addressed. Herein, we describe our efforts in developing divergent syntheses of a wide range of γ-butyrolactones and δ-ketoesters containing all-carbon quaternary centers via copper-catalyzed cyclopropanol ring opening cross couplings with 2-bromo-2,2-dialkyl esters. Our mechanistic studies reveal that unlike the previously reported cases, the formation of α,β-unsaturated enone intermediates is actually essential for the γ-butyrolactone synthesis and also contributes to the formation of the δ-ketoester product. The γ-butyrolactone synthesis is proposed to go through an intermolecular radical conjugate addition to the in situ generated α,β-unsaturated enone followed by an intramolecular radical cyclization to the ester carbonyl double bond. The reactions are effective to build all-carbon quaternary centers and have broad substrate scope.
环丙烷醇的催化开环交叉偶联反应已被用于多种β-取代羰基产物的合成。在这些开环交叉偶联反应中，α,β-不饱和烯酮副产物的形成常常与所需的交叉偶联过程相互竞争，并且一直是一个有待解决的具有挑战性的合成问题。在此，我们描述了我们通过铜催化环丙烷醇与2-溴-2,2-二烷基酯的开环交叉偶联反应，开发多种含有全碳季碳中心的γ-丁内酯和δ-酮酯的发散性合成方法的努力。我们的机理研究表明，与先前报道的情况不同，α,β-不饱和烯酮中间体的形成实际上对于γ-丁内酯的合成至关重要，并且也有助于δ-酮酯产物的形成。γ-丁内酯的合成被认为是通过分子间自由基共轭加成到原位生成的α,β-不饱和烯酮上，随后分子内自由基环化到酯羰基双键上。这些反应对于构建全碳季碳中心是有效的，并且具有广泛的底物范围。
