Gold(I)‐Catalyzed Highly Diastereo‐ and Enantioselective Cyclization–[4+3] Annulation Cascades between 2‐(1‐Alkynyl)‐2‐alken‐1‐ones and Anthranils

• Published in: Angewandte Chemie International Edition 2020-06, Vol.59 (26), p.10396-10400
• Main Authors: Kardile, Rahul Dadabhau, Chao, Tzu‐Hsuan, Cheng, Mu‐Jeng, Liu, Rai‐Shung
• Format: Article
• Language: English
• Subjects: annulation; anthranils; Catalysis; Catalysts; Chemical reactions; Enantiomers; enantioselectivity; epoxybenzoazepines; Gold; Stereoselectivity; Substrates
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202001854

This work reports gold‐catalyzed [4+3]‐annulations of 2‐(1‐alkynyl)‐2‐alken‐1‐ones with anthranils to yield epoxybenzoazepine products with excellent exo‐diastereoselectivity (dr>25:1). The utility of this new gold catalysis is manifested by applicable substrates over a broad scope. More importantly, the enantioselective versions of these [4+3]‐cycloadditions have been developed satisfactorily with chiral gold catalysts under ambient conditions (DCM, 0 °C); the ee levels range from 88.0–99.9 %. With DFT calculations, we postulate a stepwise pathway to rationalize the preferable exo‐stereoselection. Gold‐catalyzed [4+3]‐annulations of 2‐(1‐alkynyl)‐2‐alken‐1‐ones with anthranils to yield epoxybezoazepine products with excellent exo‐diastereoselectivity (dr>25:1) are reported. More importantly, enantioselective versions of these [4+3]‐cycloadditions have been developed with chiral gold catalysts under ambient conditions (DCM, 0 °C), with ee levels of 88.0–99.9 %, further highlighting their synthetic values.