Light‐Driven Carbene Catalysis for the Synthesis of Aliphatic and α‐Amino Ketones

Abstract

Single‐electron N‐heterocyclic carbene (NHC) catalysis has gained attention recently for the synthesis of C−C bonds. Guided by density functional theory and mechanistic analyses, we report the light‐driven synthesis of aliphatic and α‐amino ketones using single‐electron NHC operators. Computational and experimental results reveal that the reactivity of the key radical intermediate is substrate‐dependent and can be modulated through steric and electronic parameters of the NHC. Catalyst potential is harnessed in the visible‐light driven generation of an acyl azolium radical species that undergoes selective coupling with various radical partners to afford diverse ketone products. This methodology is showcased in the direct late‐stage functionalization of amino acids and pharmaceutical compounds, highlighting the utility of single‐electron NHC operators.

Cooperative NHC/Photoredox Catalyzed Ring‐Opening of Aryl Cyclopropanes to 1‐Aroyloxylated‐3‐Acylated Alkanes

“…Based on these results and pertinent literatures, [7,18] a mechanism is proposed (Scheme 5 d). LED irradiation leads to photoexcited 4CzIPN*, [19] which is reductively quenched by 2, generating the aryl cyclopropane radical cation IV and 4-CzIPN •À (E 1/2 red = À1.21 V vs. SCE).…”

Oxidative Radical NHC Catalysis: Divergent Difunctionalization of Olefins through Intermolecular Hydrogen Atom Transfer

“…These results indicated that the corresponding catalytic reactions might proceed through a radical process. Inspired by the previous computational studies on the NHC‐catalyzed radical reactions, [16] we performed the geometry optimizations and calculated the electronic properties of singlet state and triplet state species by using (U)M06 method [17] . The calculated Gibbs free energy profiles (Δ G ), frontier molecular orbital (FMO), [18] single electron spin density, and non‐covalent interaction (NCI) [19] are showcased in Figure 4c–f, respectively.…”

Photoinduced Acylations Via Azolium-Promoted Intermolecular Hydrogen Atom Transfer

“…13,14,31 Recent reports by our group, Hopkinson, and others on single-electron N-heterocyclic carbene catalysis highlight the utility of radical azolium species as stabilized acyl radical surrogates. [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] Due presumably to their persistence, these radical species have been shown to avoid common radical side reactivity in favor of selective radical-radical cross coupling. We hypothesized that utilizing an acyl azolium as a triplet ketone reagent would enable our desired HAT/coupling reaction manifold (Fig.…”