biostudies-literatureUnknown147(8)Yan SS1,2-Amino-difunctionalization reactions of alkenes allow the efficient introduction of different functional groups and the rapid construction of valuable functionalized amines. In this respect, we report a copper-catalyzed 1,2-amino-alkoxycarbonylation of unactivated alkenes with CO and alkylamine precursors in the presence of a Lewis acid additive. The novel protocol allows direct access to valuable β-amino acid derivatives from easily available starting materials. The presented methods feature high chemo- and regioselectivities, good functional group tolerance, and substrate scope including diverse bioactive compounds and drug-like molecules. Mechanistic studies indicate that the Lewis acid additive is the key to realizing the efficient umpolung addition of nucleophilic aminyl radicals to electron-rich alkenes, which represents an elegant activation strategy for aminyl radicals.Journal of the American Chemical Society6464-6471https://www.ebi.ac.uk/biostudies/studies/S-EPMC11869293biostudies-literatureCopper-Catalyzed Selective Amino-alkoxycarbonylation of Unactivated Alkenes with CO.PMC11869293Yan SSBeller MJackstell RfalseCopper-Catalyzed Selective Amino-alkoxycarbonylation of Unactivated Alkenes with CO.1,2-Amino-difunctionalization reactions of alkenes allow the efficient introduction of different functional groups and the rapid construction of valuable functionalized amines. In this respect, we report a copper-catalyzed 1,2-amino-alkoxycarbonylation of unactivated alkenes with CO and alkylamine precursors in the presence of a Lewis acid additive. The novel protocol allows direct access to valuable β-amino acid derivatives from easily available starting materials. The presented methods feature high chemo- and regioselectivities, good functional group tolerance, and substrate scope including diverse bioactive compounds and drug-like molecules. Mechanistic studies indicate that the Lewis acid additive is the key to realizing the efficient umpolung addition of nucleophilic aminyl radicals to electron-rich alkenes, which represents an elegant activation strategy for aminyl radicals.2025-01-01T00:00:00Z2025 Feb2025-04-22T20:04:49.055Z2025-04-06T03:03:58.708ZS-EPMC118692933996109710.1021/jacs.4c13723