Base-mediated homologative rearrangement of nitrogen-oxygen bonds of N -methyl- N -oxyamides.

Autor:	Malik M; Department of Pharmaceutical Sciences, Division of Pharmaceutical Chemistry, University of Vienna Josef-Holaubek-Platz 2 1090 Vienna Austria vittorio.pace@univie.ac.at., Senatore R; Department of Pharmaceutical Sciences, Division of Pharmaceutical Chemistry, University of Vienna Josef-Holaubek-Platz 2 1090 Vienna Austria vittorio.pace@univie.ac.at., Langer T; Department of Pharmaceutical Sciences, Division of Pharmaceutical Chemistry, University of Vienna Josef-Holaubek-Platz 2 1090 Vienna Austria vittorio.pace@univie.ac.at., Holzer W; Department of Pharmaceutical Sciences, Division of Pharmaceutical Chemistry, University of Vienna Josef-Holaubek-Platz 2 1090 Vienna Austria vittorio.pace@univie.ac.at., Pace V; Department of Pharmaceutical Sciences, Division of Pharmaceutical Chemistry, University of Vienna Josef-Holaubek-Platz 2 1090 Vienna Austria vittorio.pace@univie.ac.at.; Department of Chemistry, University of Turin Via Giuria 7 10125 Turin Italy.
Jazyk:	angličtina
Zdroj:	Chemical science [Chem Sci] 2023 Aug 29; Vol. 14 (37), pp. 10140-10146. Date of Electronic Publication: 2023 Aug 29 (Print Publication: 2023).
DOI:	10.1039/d3sc03216g
Abstrakt:	Due to the well known reactivity of C(O)-N functionalities towards canonical C1-homologating agents ( e.g. carbenoids, diazomethane, ylides), resulting in the extrusion of the N -centered fragment en route to carbonyl compounds, formal C1-insertions within N-O bonds still remain obscure. Herein, we document the homologative transformation of N -methyl- N -oxyamides - with high tolerance for diverse O -substituents - into N -acyl- N , O -acetals. Under controlled basic conditions, the N -methyl group of the same starting materials acts as a competent precursor of the methylene synthon required for the homologation. The logic is levered on the formation of an electrophilic iminium ion ( via N-O heterolysis) susceptible to nucleophilic attack by the alkoxide previously expulsed. The procedure documents genuine chemocontrol and flexibility, as judged by the diversity of substituents placed on both amide and nitrogen linchpins. The mechanistic rationale was validated through experiments conducted on D-labeled materials which unambiguously attributed the origin of the methylene fragment to the N -methyl group of the starting compounds. Competing Interests: The authors declare no competing financial interests. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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