Reactivity of steroidal 1-azadienes toward enamines: an approach to novel chiral penta- and hexacyclic steroids

• Autor(a) principal: Lopes, Susana M. M.
• Data de Publicação: 2021
• Outros Autores: Santos, Joana R. C., Pinho e Melo, Teresa M. V. D.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10316/107442; https://doi.org/10.1039/d0ob02344b
• topic: Alkenes; Amines; Aza Compounds; Catalysis; Models, Molecular; Molecular Conformation; Stereoisomerism; Steroids

The chemical behavior of steroidal N-sulfonyl-1-azadienes toward carbonyl compounds, in the presence of pyrrolidine, is described. With aldehydes, these azadienes participate in hetero-Diels-Alder reactions with the in situ generated enamines. The stereoselectivity results from the approach of the dienophiles from the less hindered α-face of the steroid, with the pyrrolidine moiety endo and retention of the enamine trans geometry. This diastereoselective synthetic methodology led to a new class of chiral pentacyclic steroids. Interestingly, the studied steroidal scaffolds follow a different mechanistic pathway with cyclic ketones. They undergo a diastereoselective annulation reaction, under enamine catalysis, affording chiral hexacyclic steroids.