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.

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

Pace, Vittorio
Last
2023-01-01

Abstract

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.
2023
Inglese
Esperti anonimi
14
37
10140
10146
7
AUSTRIA
4 – prodotto già presente in altro archivio Open Access (arXiv, REPEC…)
262
5
Malik, Monika; Senatore, Raffaele; Langer, Thierry; Holzer, Wolfgang; Pace, Vittorio
info:eu-repo/semantics/article
none
03-CONTRIBUTO IN RIVISTA::03A-Articolo su Rivista
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1947220
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