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

Preprint
cc-by Logo

Abstract

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.    

Supporting Information

Format: PDF Size: 9.6 MB   Download

How to Cite

When a peer-reviewed version of this preprint is available, this information will be updated in the information box above. If no peer-reviewed version is available, please cite this preprint using the following information:

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

Download Citation

Citation data can be downloaded as file using the "Download" button or used for copy/paste from the text window below.
Citation data in RIS format can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Zotero.

OTHER BEILSTEIN-INSTITUT OPEN SCIENCE ACTIVITIES