Research Progress on N-Heterocyclic Carbene Catalyzed Reactions for Synthesizing Ketones through Radical Mechanism

Abstract

Recently NHC-catalyzed radical cross-coupling reactions have sprung up, which provided an efficient method to access ketones from aldehydes or carboxylic acid derivatives with sp3-hybridized carbon radical precursors. It has indirectly solved the limitation of coupling partners scope in NHC umpolung catalysis of aldehydes. In this short review, we present some of the recent advances in NHC-catalyzed radical reactions, with a focus on the construction of C-C(CO) bond.

Recent advances in combining photo- and N-heterocyclic carbene catalysis

“…In recent years, the cocatalysis model has been in a state of explosion, and there are some reviews in related fields. 5 Although there have some big shoes to fill, our review focuses on the summary of the newly developed catalytic mechanism, especially in the last four years. At present, there are two main modes of NHC/photoredox dual catalysis: (1) single-electron oxidation of classical electron-rich NHC intermediates to generate ketyl radicals under photocatalytic conditions and (2) single-electron reduction of novel NHC-derived electron-deficient radical intermediates under photocatalytic conditions.…”

Synthesis of 2-pyrrolidinone derivativesviaN-heterocyclic carbene catalyzed radical tandem cyclization/coupling reactions

“…5 In comparison, NHC catalyzed single electron transfer (SET) reactions have received more attention but are still in their infancy. 6 Early in 2008, Studer and co-workers reported the pioneering work that the Breslow intermediate can be oxidized through two SET steps. 7 In 2019, Ohmiya and Nagao reported an NHC-catalyzed decarboxylative radical coupling reaction of aryl aldehydes and N -(acyloxy)phthalimides via SET from the enolate form of the Breslow intermediate to the redox N -(acyloxy)phthalimides for the efficient synthesis of functionalized ketones.…”

Synthesis of β-Ketonitriles via N-Heterocyclic-Carbene-Catalyzed Radical Coupling of Aldehydes and Azobis(isobutyronitrile)

“…Recently, Singh and co-workers reported an NHC-catalyzed nucleophilic acylation of 2-bromoacetonitrile through a umpolung strategy of aromatic aldehydes for the synthesis of β-ketonitriles, but not for α,α -disubstituted β-ketonitriles . Compared with its two-electron reactions, the NHC-catalyzed single-electron-transfer (SET) reactions have been rapidly developed and have become alternative efficient protocols to construct versatile σ-bonds . In 2019, Ohmiya and Nagao et al reported a novel NHC-catalyzed decarboxylative radical coupling reaction of aryl aldehydes and N -(acyloxy)­phthalimides that produces diverse aryl alkyl ketones via a SET process between the enolate form of Breslow intermediate and the redox N -(acyloxy)­phthalimides .…”

“…In 2019, Ohmiya and Nagao et al reported a novel NHC-catalyzed decarboxylative radical coupling reaction of aryl aldehydes and N -(acyloxy)­phthalimides that produces diverse aryl alkyl ketones via a SET process between the enolate form of Breslow intermediate and the redox N -(acyloxy)­phthalimides . Very recently, elegant NHC-catalyzed radical reactions involving Breslow-centered radical cation intermediates have been well developed by the groups of Studer, Scheidt, Chi, Ye, Ohmiya, Huang, Wang, Du, Li, Yan, and other research groups. , Inspired by these remarkable works, we envisioned that the efficient synthesis of β-ketonitriles could be realized through NHC-catalyzed radical reactions. Additionally, azobis­(isobutyronitrile) (AIBN) and its derivatives as commercially available, less toxic, and effective cyanation reagents have attracted considerable attention in organic chemistry .…”