Two-carbon ring expansion of bicyclic aziridines to oxazocines via aryne insertion into a s C–N bond

Oxazocines are medium-sized N,O-heterocycles that are motifs in reported bioactive compounds; thus, methods for their rapid preparation and functionalization are of significant interest, particularly to increase their representation in current drug libraries. In this work, a mild method to access ox...

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Detalhes bibliográficos
Autores: Rampon, D. S., Trinh, T. A., Pan, Y., Thein, S., Kailing, J. W., Guzei, I. A., Fernández López, Israel, Schomaker, J. M.
Tipo de documento: artigo
Data de publicação:2025
País:España
Recursos:Universidad Complutense de Madrid (UCM)
Repositório:Docta Complutense
Idioma:inglês
OAI Identifier:oai:docta.ucm.es:20.500.14352/131906
Acesso em linha:https://hdl.handle.net/20.500.14352/131906
Access Level:Acceso aberto
Palavra-chave:547
Química orgánica (Química)
2306 Química Orgánica
Descrição
Resumo:Oxazocines are medium-sized N,O-heterocycles that are motifs in reported bioactive compounds; thus, methods for their rapid preparation and functionalization are of significant interest, particularly to increase their representation in current drug libraries. In this work, a mild method to access oxazocines through aryne insertion into the σ C–N bond of carbamate-tethered bicyclic aziridines is described. This work unlocks a complementary reactivity mode for bicyclic aziridines via a two-carbon ring expansion, which preserves both the strained ring and its stereochemical information for further modifications. Mechanistic studies of the reaction pathway using Density Functional Theory computations indicate that oxazocine formation via nucleophilic acyl substitution of the carbonyl group of the carbamate is kinetically preferred over alternative products arising from aziridine ring-opening pathways.