Fast and scalable continuous flow synthesis of butenolides and coumarins

Autor(es)

Ferreira, Lucas Coral ; Galaverna, Renan de Souza ; Mcbride, Tom ; Silva, Rodrigo Costa e ; Browne, Duncan L. ; Pastre, Julio Cezar

• Tipo de documento: Artigo Científico
• Fonte: REACTION CHEMISTRY & ENGINEERING; v. N/A, p. 6-pg., 2025-02-10.

Resumo

Herein, we present a versatile and efficient continuous flow protocol for the synthesis of structurally diverse butenolides and coumarins through the in situ generation of acylketenes via the retro hetero-Diels-Alder reaction of dioxinones with alpha-hydroxy-ketones and salicylaldehydes, respectively. This protocol enabled the synthesis of 5 examples of butenolides with yields ranging from 30 to 91% and 16 examples of coumarins with yields ranging from 30 to 99%. The versatility and practicality of the protocol were demonstrated by the gram-scale synthesis of a biologically relevant gamma-spiro butenolide core, as well as the production of benzo-coumarins. Modern medicinal chemistry demands both scalability and the ability to synthesize structurally diverse compounds in a single synthetic platform, and our methodology effectively addresses these challenges in a fast and safer manner. (AU)

• Processo FAPESP: 21/06661-5 - Tecnologias facilitadoras para a síntese química sustentável de moléculas plataforma, novas entidades químicas e compostos bioativos
• Beneficiário: Júlio Cezar Pastre
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOEN - Jovens Pesquisadores - Fase 2
• Processo FAPESP: 23/07466-7 - Desenvolvimento de Plataformas de Auto-Otimização para a Síntese Multi-Etapas de IFAs.
• Beneficiário: Rodrigo Costa e Silva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado