On the Role of N‐Heterocyclic Carbene Salts in Alkyl Radical Generation from Alkyl Alcohols: A Computational Study

Abstract

Formation of carbon‐carbon bonds through cross‐coupling reactions using readily available substrates, like alcohols, is crucial for modern organic chemistry. Recently, direct alkyl alcohol functionalization has been achieved by the use of N‐Heterocyclic Carbene (NHC) salts via in situ formation of an alcohol‐NHC adduct and its activation by a photoredox catalyst to generate carbon‐centered alkyl radicals. Experimentally, only electron deficient NHC activators work but the reasons of this behavior remain underexplored. Herein, a DFT computational study of the mechanism of alcohol activation using up to seven NHC salts is performed to shed light into the influence of their electronic properties in the alkyl radical formation. This study demonstrates that four reaction steps are involved in the transformation and characterizes how the electronic properties of the NHC salt affect each step. A fine balance of the NHC electron‐richness is proved to be determinant for this transformation.

Revealing the Mechanism of Alcohol Dehydroxylation and C–C Bond Formation through Concerted Catalysis by Ir/Cu Bimetallic Complexes

“…Revisiting the existing literature , for activating substrates in photocatalytic organic synthesis. We propose that activation of the C–O bond in INT3 may occur through two mechanisms: SET and HAT, both of which are directly or indirectly influenced by the unique electronic properties of photocatalysts.…”

Investigating the Mechanism of Ni-Catalyzed Coupling of Photoredox-Generated Alkyl Radicals and Aryl Bromides: A Computational Study

“…In this line, the pioneering work by Molander, Kozlowski, and co-workers [24] focused on describing in detail a dual nickel/photoredox catalytic cycle and served as inspiration for further work in this field [25]. Herein, we aim to conduct a comprehensive DFT analysis of the nickel-catalyzed cross coupling of alkyl radicals and aryl bromides reported by MacMillan and co-workers, complementing our initial mechanistic study of alkyl radical generation from alcohols and NHC salts [26]. This DFT study brings up two distinct Ni-catalyzed alternatives, differing on the step where the alkyl radical is trapped by the Ni complex (Ni II vs. Ni I ) (Figure 1C).…”