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 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

Isatins As Privileged Molecules in Design and Synthesis of Spiro-Fused Cyclic Frameworks

While organocatalyzed domino reactions or "organocascade catalysis" developed into an important tool in synthetic chemistry during the past decade, the utility of N-heterocyclic carbenes (NHCs) as catalysts in domino reactions has only received growing attention in the past three years. Taking into account the unique activation modes of the substrates by NHC catalysts, it is often difficult to distinguish between a single chemical transformation and a sequential one-pot transformation. Therefore, herein we present a critical consideration of domino, cascade, and tandem catalysis in the case of NHC catalysts and highlight recent publications in this area.

N-heterocyclic carbene catalyzed domino reactions.

N‐Heterocyclic Carbene Catalyzed [4+3] Annulation of Enals and o‐Quinone Methides: Highly Enantioselective Synthesis of Benzo‐ε‐Lactones

The catalytic cyclocondensation of in situ activated α,β-unsaturated carboxylic acids was developed. N-heterocyclic carbenes efficiently catalyzed the generation of α,β-unsaturated acyl azolium intermediates from α,β-unsaturated carboxylic acids via in situ generated mixed anhydrides for the enantioselective [3+2] and [3+3] cyclocondensation with α-amino ketones and alkyl(aryl)imines, respectively. The corresponding pyrrolidinones and dihydropyridinones were isolated in good yields with high to excellent enantioselectivities.

N‐Heterocyclic Carbene Catalyzed Cyclocondensation of α,β‐Unsaturated Carboxylic Acids: Enantioselective Synthesis of Pyrrolidinone and Dihydropyridinone Derivatives

Song Ye

Papers

N‐Heterocyclic Carbene Catalyzed [4+3] Annulation of Enals and o‐Quinone Methides: Highly Enantioselective Synthesis of Benzo‐ε‐Lactones

N‐Heterocyclic Carbene Catalyzed Cyclocondensation of α,β‐Unsaturated Carboxylic Acids: Enantioselective Synthesis of Pyrrolidinone and Dihydropyridinone Derivatives

Diastereoselective synthesis of 6-trifluoromethyl-5,6-dihydropyrans via phosphine-catalyzed [4 + 2] annulation of α-benzylallenoates with ketones.

Enantioselective N-Heterocyclic Carbene Catalyzed Aza-Benzoin Reaction of Enals with Activated Ketimines†

Formal [3+2] Cycloaddition of Ketenes and Oxaziridines Catalyzed by Chiral Lewis Bases: Enantioselective Synthesis of Oxazolin-4-ones