Dual Role of Vinyl Sulfonamides as N‐Nucleophiles and Michael Acceptors in the Enantioselective Synthesis of Bicyclic δ‐Sultams

• Published in: Advanced synthesis & catalysis Vol. 360; no. 15; pp. 2885 - 2893
• Main Authors: Mulet, Cristina, Escolano, Marcos, Llopis, Sebastián, Sanz, Sergio, Ramírez de Arellano, Carmen, Sánchez‐Roselló, María, Fustero, Santos, del Pozo, Carlos
• Format: Journal Article
• Language: English
• Published: Heidelberg Wiley Subscription Services, Inc 06-08-2018
• Subjects: Adducts; bicyclic sultams; Derivatives; Enantiomers; enantioselectivity; Erosion mechanisms; intramolecular Michael addition; Michael reaction; Nitrogen; Nucleophiles; organocatalysis; Phosphazene; Racemization; Recrystallization; Rendering; Sulfonamides; Synthesis; vinyl sulfonamides
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.201800548

A new methodology for the synthesis of enantiomerically enriched bicyclic δ‐sultams is described, involving an initial organocatalytic intramolecular aza‐Michael reaction of vinyl sulfonamides bearing a conjugated ketone at a remote position. The resulting Michael adducts were then subjected to an intramolecular conjugate addition over the vinyl sulfone moiety, thus rendering the final bicyclic sultams containing two stereocenters. The key point of this strategy relies on the use of vinyl sulfonamides as both, nitrogen nucleophiles and Michael acceptors. The use of phosphazene‐derived bases avoided the racemization of the intermediate derivatives, rendering 6‐membered ring bicyclic δ‐sultams in enantiomerically enriched manner with a small erosion of enantiopurity. Anyway, after recrystallization, final sultams were obtained in almost enantiomerically pure form. Nevertheless, the enantioselective synthesis of either 5‐membered ring products or benzofused derivatives was found to be out of the scope of our strategy.