The successful isolation and characterization of an N-heterocyclic carbene in 1991 opened up a new class of organic compounds for investigation. From these beginnings as academic curiosities, N-heterocyclic carbenes today rank among the most powerful tools in organic chemistry, with numerous applications in commercially important processes. Here we provide a concise overview of N-heterocyclic carbenes in modern chemistry, summarizing their general properties and uses and highlighting how these features are being exploited in a selection of pioneering recent studies.

An overview of N-heterocyclic carbenes

Organocatalytic Reactions Enabled by N-Heterocyclic Carbenes.

The umpolung strategy encompasses all the methods that make organic molecules react in an inverse manner compared to their innate polarity-driven reactivity. This concept entered the field of organocatalysis when it was recognized that N-heterocyclic carbenes (NHCs) can provide catalytic access to acyl anion equivalents. Since then, tremendous efforts have followed to develop a broad variety of NHC-catalyzed reactions. In addition to this, more recent research developments have shown that other families of organocatalysts are also able to mediate transformations in which inversion of polarity is involved. This tutorial review aims at offering a didactic overview of organocatalytic umpolung and should serve as an inspiration for further progress in this field.

Organocatalytic umpolung: N-heterocyclic carbenes and beyond

Transition-metal-catalyzed cross-coupling reactions have been well-established as indispensable tools in modern organic synthesis. One of the major research goals in cross-coupling area is expanding the scope of the coupling partners. In the past decade, diazo compounds (or their precursors N-tosylhydrazones) have emerged as nucleophilic cross-coupling partners in C–C single bond or C═C double bond formations in transition-metal-catalyzed reactions. This type of coupling reaction involves the following general steps. First, the organometallic species is generated by various processes, including oxidative addition, transmetalation, cyclization, C–C bond cleavage, and C–H bond activation. Subsequently, the organometallic species reacts with the diazo substrate to generate metal carbene intermediate, which undergoes rapid migratory insertion to form a C–C bond. The new organometallic species generated from migratory insertion may undergo various transformations. This type of carbene-based coupling has proven...

Transition-Metal-Catalyzed Cross-Couplings through Carbene Migratory Insertion

Efficient, selective and sustainable catalysis of carbon dioxide

An Overview of N-Heterocyclic Carbenes

A highly enantioselective N-heterocyclic carbene (NHC) catalyzed formal [3+2] annulation of α,β-unsaturated aldehydes with azaaurones or aurone generating spiro-heterocycles has been developed. The protocol represents a unique NHC-activation-based approach to access spiro-heterocyclic derivatives bearing a quaternary stereogenic center with high optical purity (up to 95 % ee).

N-heterocyclic carbene catalyzed formal [3+2] annulation reaction of enals: an efficient enantioselective access to spiro-heterocycles.

Faster, higher, stronger! The N-heterocyclic carbene (NHC) catalyzed diastereo- and enantioselective hydroacylation of cyclopropenes affords structurally valuable acylcyclopropanes. A new family of electron-rich, 2,6-dimethoxyphenyl-substituted NHCs induces excellent reactivity and enantioselectivity. Preliminary kinetic studies unambiguously demonstrated the superiority of this family of catalysts over known NHCs in this challenging transformation.

Designing N-heterocyclic carbenes: simultaneous enhancement of reactivity and enantioselectivity in the asymmetric hydroacylation of cyclopropenes.

New hydroacylation catalysts: Highly electron-rich N-heterocyclic carbenes (NHCs) facilitate the intermolecular hydroacylation of unstrained olefins. This unprecedented organocatalytic coupling joins simple and abundant aldehydes and styrenes to yield valuable ketone products. EWG=electron-withdrawing group, EDG=electron-donating group.

Michael Schedler

Papers

An overview of N-heterocyclic carbenes

An Overview of N-Heterocyclic Carbenes

N-heterocyclic carbene catalyzed formal [3+2] annulation reaction of enals: an efficient enantioselective access to spiro-heterocycles.

Designing N-heterocyclic carbenes: simultaneous enhancement of reactivity and enantioselectivity in the asymmetric hydroacylation of cyclopropenes.

NHC-catalyzed hydroacylation of styrenes.