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

Submitting author affiliation:
Unicamp, Campinas, Brazil

Beilstein Arch. 2023, 202366. https://doi.org/10.3762/bxiv.2023.66.v1

Published 28 Dec 2023

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We report herein an enantioselective palladium-catalyzed Heck-Matsuda reaction for the desymmetrization of N-protected 2,5-dihydro-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-γ-lactams via Heck arylation followed by a sequential Jones’ oxidation. The overall method displays 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.

Keywords:  Desymmetrization; enantioselective Heck-Matsuda reaction; lactam synthesis; N,N-ligands; palladium.    

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de Oliveira Junior, A. G.; Wang, M. F.; Carmona, R. C.; Lustosa, D. M.; Gorbatov, S. A.; Correia, C. R. D. Beilstein Arch. 2023, 202366. doi:10.3762/bxiv.2023.66.v1

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