Access to Enantioenriched Spiro‐ϵ‐Lactam Oxindoles by an N‐Heterocyclic Carbene‐Catalyzed [4+3] Annulation of Flexible Oxotryptamines with Enals

• Published in: Chemistry : a European journal Vol. 25; no. 48; pp. 11223 - 11227
• Main Authors: Liu, Dehai, Hu, Zhouli, Zhang, Yuxia, Gong, Minghua, Fu, Zhenqian, Huang, Wei
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 27.08.2019; Wiley Subscription Services, Inc
• Subjects: [4+3] annulation; Amides; Chemical reactions; Chemistry; Chemistry, Multidisciplinary; Enantiomers; flexible oxotryptamines; N-heterocyclic carbenes; Organic chemistry; organocatalysis; Physical Sciences; Science & Technology; spiro-ϵ-lactam oxindoles; Substrates; NHC CATALYSIS; ACTIVATION; ASYMMETRIC-SYNTHESIS; ENANTIOSELECTIVE SYNTHESIS; organocatalysis; flexible oxotryptamines; [4+3] annulation; KINETIC RESOLUTION; CONSTRUCTION; GENERATION; STEREOSELECTIVE-SYNTHESIS; N-heterocyclic carbenes; spiro-epsilon-lactam oxindoles; DEAROMATIZATION; spiro-ϵ-lactam oxindoles
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201903144

Oxotryptamines were firstly used as flexible four‐atom synthons in an NHC‐catalyzed formal [4+3] annulation, providing a novel enantioselective method to access structurally diverse spiro‐ϵ‐lactam oxindoles with excellent enantioselectivities. This metal‐free reaction features a broad substrate scope, excellent functional‐group tolerance and proceeds under mild reaction conditions. Importantly, enantiopure privileged hexahydropyrroloindoles could be easily constructed by a one‐pot process from the resulting spiro‐ϵ‐lactam oxindoles. Organocatalysis: Oxotryptamine was used as a flexible four‐atom synthon in an NHC‐catalyzed formal [4+3] annulation, providing an enantioselective method to access structurally diverse spiro‐ϵ‐lactam oxindoles with excellent enantioselectivities. This metal‐free reaction features a broad substrate scope, excellent functional‐group tolerance and proceeds under mild reaction conditions (see scheme).