Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck-Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

Author(s)

de Oliveira Jr, Arnaldo G. ; Wang, Marti F. ; Carmona, Rafaela C. ; Lustosa, Danilo M. ; Gorbatov, Sergei A. ; Correia, Carlos R. D.

• Document type: Journal article
• Source: Beilstein Journal of Organic Chemistry; v. 20, p. 10-pg., 2024-04-29.

Abstract

We report herein an enantioselective palladium -catalyzed Heck-Matsuda reaction for the desymmetrization of N -protected 2,5dihydro-1 H -pyrroles with aryldiazonium salts, using the chiral N , N -ligand ( S )-PyraBox. This strategy has allowed straightforward access to a diversity of 4-aryl- gamma -lactams via Heck arylation followed by a sequential Jones oxidation. The overall method displays a broad scope and good enantioselectivity, favoring the ( R ) enantiomer. The applicability of the protocol is highlighted by the efficient enantioselective syntheses of the selective phosphodiesterase-4-inhibitor rolipram and the commercial drug baclofen as hydrochloride. (AU)

• FAPESP's process: 14/25770-6 - New frontiers in cross-coupling reactions promoted by palladium: combining enantioselective catalysis, C-H activations, new materials and in flux reactions aiming at high efficiency and sustainability in synthetic processes
• Grantee: Carlos Roque Duarte Correia
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/00271-8 - Enantioselective Synthesis of Heterocylces via Intramolecular and Desymmetrizations Reacions Using Arenediazonium Salts
• Grantee: Rafaela Costa Carmona
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 17/21494-2 - Synthesis of pharmacologically active compounds by the enantioselective Heck-Matsuda reaction and novel studies concerning the enantioselective acylation of cyclopentenes and cyclohexene compounds
• Grantee: Martí Fernández Wang
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 23/00025-5 - Autosustenable enantioselective Heck-Matsuda reactions via in situ generated aryldiazonium salts directly from anilines or nitroaryl derivatives in a one-pot strategy.
• Grantee: Sergei Gorbatov
• Support Opportunities: Scholarships in Brazil - Post-Doctoral