Allenamides Playing Domino: A Redox‐Neutral Photocatalytic Synthesis of Functionalized 2‐Aminofurans

Abstract

A photoredox catalytic synthesis of functionalized 2-aminofurans is proposed starting from α-halo carbonyl substrates and N-allenamides. The protocol proves to be efficient and sustainable thanks to: i) the use of visible light as green energy source, ii) the redox-neutral nature of the transformation, allowing to avoid additives and strong oxidants, iii) the mild reaction conditions and the functional groups tolerance, iv) the low photocatalyst loading and the absence of excess reagents, v) the one-pot formation of three new bonds in a domino sequence. According to our mechanistic hypothesis, the transformation is configured as a double radical-polar crossover reaction, in which the photocatalyst is excited, oxidized and reduced twice for each molecule of 2-aminofuran produced. The novelty of the designed synthetic approach also lies in the use of Nallenamides as substrates, which, after the addition of the first electrophilic radical, preserve a further reactive π-system, making possible the addition of a second α-keto radical and enabling the installation of a keto functionality at a remote position. The good yields, the broad scope, and the possibility to further synthetically elaborate the obtained furans make this protocol particularly promising for the construction of useful products.

Construction of C–N and C–O bonds based on N-allenamide functionalization

“…A year later, Quintavalla, Lombardo and coworkers 31 described a photoredox-catalyzed synthesis of 2-aminofurans 95 from N -allenamide 6 . Homolytic cleavage of α-halocarbonyl species led to the formation of radicals 96 that were added to the proximal position of the N -allenamide to form radical species 97 .…”

Selective Hydrofunctionalization of N-Allenyl Derivatives with Heteronucleophiles Catalyzed by Brønsted Acids

“…As part of our ongoing research interests in the reactivity of alkenyl-systems and, in particular, of N -allenyl substrates, we focused our efforts on the development of an effective, simple, inexpensive, and sustainable synthetic approach to γ-oxygenated enamides starting from N -substituted allenes and alcohols (Scheme d). Aiming to avoid the use of metal-based catalysts, we envisaged that a Brønsted acid could mimic the activation ability of some metal complexes, exploiting the electron-rich nature of the allenamides (Scheme ).…”

PhI(OAc)2-Mediated Regioselective Hydrothiolation of Allenamides with Thiophenol via a Radical Process: Synthesis of Vinyl Sulfides

“…These radical annulations involving allenamides were carried out using stoichiometric toxic reagents and mostly at elevated temperatures, which make the process undesirable. On the other hand, the limited examples of metallo- and organo-photoredox-catalyzed alkyl radical additions of allenamides are governed mainly by toxic and expensive transition metals . Therefore, the development of new methods for the radical reaction of allenamides is still highly desired.…”