Site-Selective, Photocatalytic Vinylogous Amidation of Enones

Abstract

Despite the broad interest in organic compounds possessing a γ-aminocarbonyl motif, limited strategies for their synthesis have been reported. Herein, we describe a mild and efficient method for the site-selective amidation of unsaturated enones with electrophilic N-centered radicals as a key intermediate. The photocatalytic vinylogous reaction of dienolates with N-amino pyridinium salts affords γ-amido carbonyl compounds. This process is high-yielding, scalable, and tolerates a broad range of unsaturated α,β-unsaturated carbonyls, including biologically relevant compounds, as starting materials.T he concept of vinylogy, established by Fuson in 1935, 1 postulates that the influence of a functional group can be propagated through a conjugated system of unsaturated bonds. This phenomenon is particularly important for the functionalization of α,β-unsaturated carbonyl compounds, which are versatile starting materials in organic synthesis. 2−15 Typically, in vinylogous reactions, π-extended carbonyl derivatives of type I are transformed into dienolates II that contain two nucleophilic sites (Scheme 1). Consequently, the addition of electrophiles can occur at either α-position (III) or more remote γ-position

Recent Uses of Photogenerated Oxygen-Centered Radicals in Intermolecular C–O Bond Formation

“…35 However, it was much less studied regarding reactivity towards radicals. 36 In particular, a selective -alkoxylation of enals was not reported to date. 37 We therefore decided to prepare silyl dienol ethers 56 from the corresponding enals and to perform their alkoxylation under visible-light mediated conditions using our N-alkoxy 4-cyanopyridinium salts 42 as sources of RO • radicals (Scheme 21).…”

Electrochemical Benzylic C–H Amination via N-Aminopyridinium

“…N -Aminopyridinums are versatile structure motifs which can be readily converted into nitrogen-containing molecules . These salts can be used as pyridylation reagents, and precursors of N -centered radicals . In addition, N -aminopyridiniums can also serve as unique bifunctional reagents to enable the difunctionalization of alkenes or propellane to produce molecules containing both amine and pyridine groups.…”

N-Iminopyridinium Compounds in Giese Reaction: Photoinduced Homolytic N–N and C–C Bond Cleavage for Cyanoalkyl Radical Generation

“…Recent research on the N–N reductive cleavage of N -nitrogen-substituted pyridinium salts has garnered attention for its ability to produce N -centered radicals, demonstrating significant potential for diverse applications in organic synthesis. A photoinduced redox reaction employing Ru, Ir, and an organocatalyst provided the aminyl or amidyl radicals for C–H amidation of arenes and functionalization of alkenes such as amination, aziridination, aminopyridylation, and various annulation reactions . The bifunctionality of N -aminopyridinium compounds in aminopyridylation especially makes them a unique N atom source superior to that of traditional aminating reagents.…”