Department of Chemistry, Center for Molecular Innovation and Drug Discovery, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208, USA.
Department of Chemistry, Oregon State University, 153 Gilbert Hall, Corvallis, OR, 97331, USA.
Angew Chem Int Ed Engl. 2019 Apr 23;58(18):5941-5945. doi: 10.1002/anie.201900600. Epub 2019 Mar 27.
A direct decarboxylative strategy for the generation of aza-o-quinone methides (aza-o-QMs) by N-heterocyclic carbene (NHC) catalysis has been discovered and explored. This process requires no stoichiometric additives in contrast with current approaches. Aza-o-QMs react with trifluoromethyl ketones through a formal [4+2] manifold to access highly enantioenriched dihydrobenzoxazin-4-one products, which can be converted to dihydroquinolones through an interesting stereoretentive aza-Petasis-Ferrier rearrangement sequence. Complementary dispersion-corrected density functional theory (DFT) studies provided an accurate prediction of the reaction enantioselectivity and lend further insight to the origins of stereocontrol. Additionally, a computed potential energy surface around the major transition structure suggests a concerted asynchronous mechanism for the formal annulation.
已发现并探索了通过 N-杂环卡宾（NHC）催化生成氮杂-o-醌甲川（aza-o-QM）的直接脱羧策略。与当前方法相比，该过程不需要使用化学计量添加剂。氮杂-o-QM 与三氟甲基酮通过形式上的 [4+2] 反应途径反应，以获得高对映体过量的二氢苯并恶嗪-4-酮产物，通过有趣的立体保留氮杂-Petasis-Ferrier 重排序列，这些产物可以转化为二氢喹诺酮。补充的色散校正密度泛函理论（DFT）研究对反应对映选择性进行了准确预测，并进一步深入了解了立体控制的起源。此外，主要过渡态周围的计算势能面表明，形式环合的反应是协同异步机制。
