Radical Acylation of Alkenes by NHC‐Organocatalysis

Abstract

N‐Heterocyclic carbene (NHC) catalyzed radical‐radical reactions have been proven to be powerful strategies for assembling ketyl‐containing compounds via single electron transfer (SET) pathway under either thermal conditions or photoredox conditions. In this context, acylation of alkenes via radical relay under NHC‐organocatalysis has also opened a new window for the difunctionalization of alkenes to construct valuable molecules in organic synthesis. In this review, the advances and progress of the acylation of alkenes via NHC‐organocatalysis were summarized according to different ways of generation of the key NHC‐bound ketyl‐type radicals. Furthermore, reaction scopes, limitations and mechanisms were discussed based on reaction types and catalytic systems. Conclusions and perspectives were also put forward at the end.

Radical Reactions with N-Heterocyclic Carbene (NHC)-Derived Acyl Azoliums for Access to Multifunctionalized Ketones

“…The NHC-bound acylazolium intermediate bears a structure similar to ketones, which can be named as ketone-like molecules, leading to some similar reactivity. The excited acylazolium intermediates can be generally obtained from two pathways: the direct stimulation of acylazolium via light irradiation and the energy transfer process between acylazolium and a photoexcited photocatalyst …”

“…Later, the SET oxidation reactions of the Breslow intermediates were extensively explored by Rovis, Ye, Omiya, Chi, and others . A number of critical reviews and tutorial chapters have been documented on the radical reactions involving Breslow intermediate oxidations (Scheme , left) . In contrast, the SET reduction reaction of the acylazolium intermediate that formed in NHC catalytic processes has not been disclosed until the year 2020, when Scheidt and Studer groups independently reported the radical coupling reaction of an alkyl radical with the NHC-bound ketyl radical for ketone synthesis (Scheme , right).…”

1H-1,2,3-Triazol-5-ylidenes as Catalytic Organic Single-Electron Reductants

“…In organocatalysis, most of the applications were the result of their ability to behave as two-electron donors, as exemplified by their use in triggering the umpolung reactivity of aldehydes via Breslow Intermediates (BIs) . More recently, single-electron processes in which BI-enolates behave as organic reductants have been established . Among these reports, our group recently discovered that 1 H -1,2,3-triazol-5-ylidenes (a subclass of mesoionic carbenes) A led to the formation of strongly reducing Breslow enolates ( E 1/2 < −1.9 V vs SCE) which can readily reduce aryl iodide and induce several different catalytic processes .…”

Synthesis of γ-Oxo-phosphonates via N-Heterocyclic Carbene-Catalyzed Acylphosphorylation of Alkenes

“…N -Heterocyclic carbene (NHC) radical organocatalysis has recently emerged as a powerful platform for the invention of versatile transformations. − Because of the strong reducing capabilities of the Breslow enolate A , an interesting application of this chemistry is the oxidative generation of NHC-derived persistent ketyl radical B for subsequent coupling reactions (Scheme B). , Pioneering work by Ohmiya et al showcased the single-electron reduction of redox-active esters, which yielded alkyl radicals and enabled the synthesis of sterically hindered ketones from a wide range of aldehydes . Ongoing work by us and the Ohmiya, Li, and Ye groups has extended the application of this organocatalytic strategy to access valuable radicals, including fluoroalkyl radicals, aryl radicals, N radicals, and O radicals.…”