Iron-Catalyzed Carbamoylation of Enamides with Formamides as a Direct Approach to N-Acyl Enamine Amides

Abstract

The robustness of iron catalysis enabling the oxidative coupling reactions of enamides with formamides is described. Routing from readily accessible feedstocks, the efficient approach is implemented to furnish a broad array of value-added N-acyl enamine amide derivatives, which serve as versatile precursors of biologically relevant N-heterocycles including pyrimidin-4-ones and 4-hydroxypyridin-2-ones. Preliminary mechanistic studies supported the notion that this direct carbamoylation reaction proceeded through an aminoacyl radical species.

Iron catalyzed β-C(sp2)–H alkylation of enamides

“…These results indicate that the reaction might proceed through a radical pathway. Based on these experimental results and previous reports, 14,19 Please do not adjust margins Please do not adjust margins valent iron complex, Fe II is regenerated leading to the formation of a carbocation species C and its corresponding resonance structure C'. Finally, a base mediated deprotonation furnishes the desired alkylated product derivative 3 with a total transdiastereoselectivity (R 1 ≠ O).…”

“…), solvent (3.0 mL), 100 °C, 16 h, under Ar. b Yields determined by 19 F NMR analysis of the crude mixture using α,α,α-trifluorotoluene as an internal standard. To our delight, most of the reactions proceeded smoothly to afford the corresponding -alkylated enamides 3 in moderate to good yields.…”

“…Spectra were calibrated using the corresponding nondeuterated solvent. 19 F NMR (235 or 376 MHz) chemical shifts are given in ppm. High-resolution mass spectra were recorded with a Bruker maXis ESI qTOF ultrahigh-resolution mass spectrometer coupled to a Dionex Ultimate 3000 RSLC system.…”

“…When appropriate or in the event of ambiguous proton and carbon, assignments were established using19 F NMR and Heteronuclear Multiple-bond Correlation (HMBC). Unless otherwise stated,13 C and19 F spectra were acquired on a broad band decoupled mode 1.…”

“…When appropriate or in the event of ambiguous proton and carbon, assignments were established using19 F NMR and Heteronuclear Multiple-bond Correlation (HMBC). Unless otherwise stated,13 C and19 F spectra were acquired on a broad band decoupled mode 1. H NMR (250, 400 or 700 MHz) chemical shift values are listed in parts per million (ppm), downfield from TMS as the internal standard or relative to the corresponding nondeuterated solvent.…”