Asymmetric Synthesis of Spirobenzazepinones with Atroposelectivity and Spiro-1,2-Diazepinones by NHC-Catalyzed [3+4] Annulation Reactions

• Published in: Angewandte Chemie International Edition 2016-09, Vol.55 (37), p.11110-11114
• Main Authors: Wang, Lei, Li, Sun, Blümel, Marcus, Philipps, Arne R., Wang, Ai, Puttreddy, Rakesh, Rissanen, Kari, Enders, Dieter
• Format: Article
• Language: English
• Subjects: 1,2-diazepinone; 2-diazepinone; asymmetric synthesis; benzazepinone; N-heterocyclic carbene; spiro compound
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201604819

A strategy for the NHC‐catalyzed asymmetric synthesis of spirobenzazepinones, spiro‐1,2‐diazepinones, and spiro‐1,2‐oxazepinones has been developed via [3+4]‐cycloaddition reactions of isatin‐derived enals (3C component) with in‐situ‐generated aza‐o‐quinone methides, azoalkenes, and nitrosoalkenes (4atom components). The [3+4] annulation strategy leads to the seven‐membered target spiro heterocycles bearing an oxindole moiety in high yields and excellent enantioselectivities with a wide variety of substrates. Notably, the benzazepinone synthesis is atroposelective and an all‐carbon spiro stereocenter is generated. Spiro via [3+4]: The asymmetric NHC‐catalyzed [3+4] annulation of isatin‐derived enals and aryl sulfonamides or tosyl hydrazones leads to spirobenzazepinones with atroposelectivity, or to spiro‐1,2‐diazepinones bearing an oxindole moiety in high yields and excellent enantioselectivities with a wide variety of substrates.