Mechanochemical Asymmetric Cross‐Dehydrogenative Coupling Reaction: Liquid‐Assisted Grinding Enables Reaction Acceleration and Enantioselectivity Control

作者：Jingbo Yu, Ping Ying, Hao Wang, Keyu Xiang, Weike Su · 发表于：Advanced Synthesis & Catalysis · 年份：2019 · DOI：10.1002/adsc.201901363 · 被引用次数：39 · 研究领域：Alkaloids: synthesis and pharmacology、Catalytic C–H Functionalization Methods、Axial and Atropisomeric Chirality Synthesis

Abstract We report here a mechanochemical protocol for asymmetric cross‐dehydrogenative coupling (CDC) reaction of unreactive 3‐arylmethyl indoles with 1,3‐dicarbonyl by liquid‐assisted grinding. Small drops of liquid additive n ‐butyl acetate ( n ‐BuOAc) are key to achieve high yield and enantioselectivity in this transformation. The catalyst can be lowered to 5 mol% and reused for three times. Pharmaceutical useful chiral dihydrocoumarins are further achieved through one‐pot tandem asymmetric CDC and cyclization with excellent enantioselectivities. Experimental and computational studies on the reaction mechanism suggest that n ‐BuOAc is participated to the catalytic cycle, forming a chiral metal species during the reaction process and thereby revealed the origin of stereoselectivity. magnified image