Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada.
Department of Computer Science, University of Toronto, 214 College St., Toronto, Ontario M5T 3A1, Canada.
J Am Chem Soc. 2020 Jul 29;142(30):13246-13254. doi: 10.1021/jacs.0c06904. Epub 2020 Jul 15.
The ability to understand and predict reactivity is essential for the development of new reactions. In the context of Ni-catalyzed C(sp)-O functionalization, we have developed a unique strategy employing activated cyclopropanols to aid the design and optimization of a redox-active leaving group for C(sp)-O arylation. In this chemistry, the cyclopropane ring acts as a reporter of leaving-group reactivity, since the ring-opened product is obtained under polar (2e) conditions, and the ring-closed product is obtained under radical (1e) conditions. Mechanistic studies demonstrate that the optimal leaving group is redox-active and are consistent with a Ni(I)/Ni(III) catalytic cycle. The optimized reaction conditions are also used to synthesize a number of arylcyclopropanes, which are valuable pharmaceutical motifs.
理解和预测反应性对于开发新反应至关重要。在镍催化的 C(sp)-O 功能化的背景下，我们开发了一种独特的策略，利用活化的环丙醇来辅助设计和优化用于 C(sp)-O 芳基化的氧化还原活性离去基团。在这种化学中，环丙烷环充当离去基团反应性的报告基团，因为在极性（2e）条件下获得开环产物，而在自由基（1e）条件下获得闭环产物。机理研究表明，最佳离去基团是氧化还原活性的，与 Ni(I)/Ni(III)催化循环一致。优化的反应条件也用于合成许多芳基环丙烷，它们是有价值的药物基序。
