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Recent advances in the chemistry and applications of N-heterocyclic carbenes

Abstract

N-Heterocyclic carbenes, despite being isolated and characterized three decades ago, still capture scientists’ interest as versatile, modular and strongly coordinating moieties. In the last decade, driven by the increasingly refined fundamental understanding of their behaviour, the emergence of new carbene frameworks and cogent sustainability issues, N-heterocyclic carbenes have experienced a tremendous increase in utilization across several disparate fields. In this Review, a concise overview of N-heterocyclic carbenes encompassing their history, properties and applications in transition metal catalysis, on-surface chemistry, main group chemistry and organocatalysis is provided. Emphasis is placed on developments emerging in the last seven years and on envisaging future directions.

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Fig. 1: Timeline of the synthesis and applications of N-heterocyclic carbenes.
Fig. 2: Recent key advances, structural features and selected N-heterocyclic carbenes classes.
Fig. 3: Applications of N-heterocyclic carbenes in transition metal catalysis and surface modification.
Fig. 4: On-surface applications of N-heterocyclic carbenes.
Fig. 5: N-Heterocyclic carbene-induced advances in main group chemistry.
Fig. 6: Present and future organocatalytic applications of N-heterocyclic carbenes.

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Acknowledgements

Financial support by the Deutsche Forschungsgemeinschaft (SFB 858, Leibniz Award) is gratefully acknowledged.

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Glossary

HOMO

Highest occupied molecular orbital. Its energy defines the overall nucleophilic character of the species.

LUMO

Lowest unoccupied molecular orbital. Its energy defines the overall electrophilic character of the species.

Remote carbenes

N-Heterocyclic carbenes in which the carbene atom is not directly adjacent to any heteroatom.

CAACs

Cyclic (alkyl)(amino)carbenes. Cyclic species that possess a single nitrogen and a sp3-hybridized carbon adjacent to the singlet carbene centre.

Mesoionic carbenes

Special class of N-heterocyclic carbenes bearing both negative and positive delocalized charges, which can be neither satisfactorily represented by a totally covalent nor by a single polar structure.

DACs

N,N′-diamidocarbenes. N-Heterocyclic carbene species that features two carbonyl amido groups within the cyclic structure.

Schrock carbenes

Classification of carbenes binding to a metal, characterized by strong donation towards a high-oxidation-state metal, preferentially an early transition metal in the presence of π-donor ligands. The typical decoration of the carbene carbon involves hydrogen or alkyl substitution.

Fischer carbenes

Classification of carbenes binding to a metal, characterized by enhanced electrophilic character towards a low-oxidation-state metal, preferentially a middle or late transition metal in the presence of π-accepting ligands. The typical decoration of the carbene carbon involves a π-donating substituent (e.g. alkoxy, alkylamino).

Backbonding

The π-electron donation from a metal centre to an empty orbital of appropriate symmetry of the ligand (also known as π-back-donation).

Umpolung

The reversal of the intrinsic polarity of a functional group within a synthetic method.

Breslow intermediate

Key enaminol intermediate originating from the nucleophilic attack of an N-heterocyclic carbene onto a carbonyl, followed by proton transfer. The Breslow intermediate possesses nucleophilic character at the once-aldehydic carbon.

Ketyl radical

Radical anion species formed by single-electron reduction of a ketone.

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Bellotti, P., Koy, M., Hopkinson, M.N. et al. Recent advances in the chemistry and applications of N-heterocyclic carbenes. Nat Rev Chem 5, 711–725 (2021). https://doi.org/10.1038/s41570-021-00321-1

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