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

N-Heterocyclic Carbenes in Late Transition Metal Catalysis

The chemistry of heterocyclic carbenes has experienced a rapid development over the last years. In addition to the imidazolin-2-ylidenes, a large number of cyclic diaminocarbenes with different ring sizes have been described. Aside from diaminocarbenes, P-heterocyclic carbenes, and derivatives with only one, or even no heteroatom within the carbene ring are known. New methods for the synthesis of complexes with N-heterocyclic carbene ligands such as the oxidative addition or the metal atom template controlled cyclization of β-functionalized isocyanides have been developed recently. This review summarizes the new developments regarding the synthesis of N-heterocyclic carbenes and their metal complexes.

Heterocyclic Carbenes: Synthesis and Coordination Chemistry

Organocatalytic Reactions Enabled by N-Heterocyclic Carbenes.

The total synthesis of natural products and biologically active compounds, such as pharmaceuticals and agrochemicals, has reached an extraordinary level of sophistication. We are, however, still far away from the 'ideal synthesis' and the state of the art is still frequently hampered by lengthy protecting-group strategies and costly purification procedures derived from the step-by-step protocols. In recent years several new criteria have been brought forward to solve these problems and to improve total synthesis: atom, step and redox economy or protecting-group-free synthesis. Over the past decade the research area of organocatalysis has rapidly grown to become a third pillar of asymmetric catalysis standing next to metal and biocatalysis, thus paving the way for a new and powerful strategy that can help to address these issues - organocatalytic cascade reactions. In this Review we present the first applications of such asymmetric organocascade reactions to the total synthesis of natural products.

Organocatalytic cascade reactions as a new tool in total synthesis

In the investigation of efficient chemical transformations, the carbon-carbon bond-forming reactions play an outstanding role. In this context, organocatalytic processes have achieved considerable attention. 1 Beside their facile reaction course, selectivity, and environmental friendliness, new synthetic strategies are made possible. Particularly, the inversion of the classical reactivity (Umpolung) opens up new synthetic pathways. 2 In nature, the coenzyme thiamine (vitamin B1), a natural thiazolium salt, utilizes a catalytic variant of this concept in biochemical processes as nucleophilic acylations. 3 The catalytically active species is a nucleophilic carbene. 4

Organocatalysis by N-Heterocyclic Carbenes

https://www.rsc.org/suppdata/cc/b8/b809913h/b809913h.pdf

Asymmetric intermolecular Stetter reactions catalyzed by a novel triazolium derived N-heterocyclic carbene

A direct intermolecular cross-benzointype condensation catalyzed by an N-heterocyclic carbene has been developed. The cross-coupling of commercially available aromatic aldehydes and trifluoromethyl ketones results in α-hydroxy-α-trifluoromethyl ketones bearing a quaternary stereo-center with excellent chemoselectivity and good to excellent yields.

A Direct Intermolecular Cross-Benzoin Type Reaction: N-Heterocyclic Carbene-Catalyzed Coupling of Aromatic Aldehydes with Trifluoromethyl Ketones

An efficient N-heterocyclic carbene (NHC)-catalyzed nucleophilic acylation of trifluoromethyl ketimines has been developed. The combination of N-aryl trifluoromethyl ketimines with various furan-2-carbaldehydes leads chemoselectively to the corresponding α-amino-a-trifluoromethyl ketones in moderate to very good yields (32-87%) providing ready access to this pharmaceutically important class of compounds.

N-Heterocyclic Carbene Catalyzed Nucleophilic Acylation of Trifluoromethyl Ketimines

The asymmetric intermolecular Stetter reaction is catalyzed by a novel triazolium salt derived N-heterocyclic carbene leading to 1,4-diketones in moderate to excellent yields (49–98%) and moderate to good enantioselectivities (56–78% ee), which could be enhanced by one recrystallization to excellent levels (90–99% ee).

Alexander Henseler

Papers

Organocatalysis by N-Heterocyclic Carbenes

Asymmetric intermolecular Stetter reactions catalyzed by a novel triazolium derived N-heterocyclic carbene

A Direct Intermolecular Cross-Benzoin Type Reaction: N-Heterocyclic Carbene-Catalyzed Coupling of Aromatic Aldehydes with Trifluoromethyl Ketones

N-Heterocyclic Carbene Catalyzed Nucleophilic Acylation of Trifluoromethyl Ketimines

Asymmetric Intermolecular Stetter Reactions Catalyzed by a Novel Triazolium Derived N‐Heterocyclic Carbene.