NHC Catalysis Research Articles

ChemInform Abstract: Exploring the Vinylogous Reactivity of Cyclohexenylidene Malononitriles: Switchable Regioselectivity in the Organocatalytic Asymmetric Addition to Enals Giving Highly Enantioenriched Carbabicyclic Structures.

AbstractA two‐step, one‐pot sequence under chiral amine—NHC catalysis allows the approach to spiro[4.5]decanone structures in a diastereoselective manner with high e.e.

N-Heterocyclic carbene-catalyzed enantioselective annulations: a dual activation strategy for a formal [4+2] addition for dihydrocoumarins.

A highly efficient asymmetric formal [4+2] annulation for the synthesis of dihydrocoumarins has been developed via an in situ activated NHC catalysis. Both electrophilic and nucleophilic species are generated in situ simultaneously whereby acyl imidazoles facilitated rapid formation of an NHC-enolate intermediate to afford the [4+2] dihydrocoumarin adducts.

ChemInform Abstract: Direct Allylation of in situ Generated Aldehyde Acyl Anions by Synergistic NHC and Palladium Catalysis.

AbstractStarting from easily accessible allylic carbonates and aldehydes, an efficient access to β,γ‐unsaturated ketones under mild reaction conditions is provided.

Cascade [4+2] Annulation by NHC Catalysis

Cascade [4+2] Annulation by NHC Catalysis

Enantioselective N-heterocyclic carbene-catalyzed β-hydroxylation of enals using nitroarenes: an atom transfer reaction that proceeds via single electron transfer.

A novel oxidative N-heterocyclic carbene-catalyzed reaction pathway has been discovered. Alkyl and aryl enals undergo β-hydroxylation via oxygen atom transfer from electron-deficient nitrobenzenes, followed by trapping of the resultant acyl azolium by the solvent. The proposed mechanism involves a single electron transfer event to initiate the reaction followed by radical recombination. This represents a profound mechanistic departure from the established two-electron disconnects in NHC catalysis.

Asymmetric synthesis of highly substituted β-lactones through oxidative carbene catalysis with LiCl as cooperative Lewis acid.

The reaction of enals with β-diketones, β-ketoesters, and malonates bearing a β-oxyalkyl substituent at the α-position by oxidative NHC catalysis to provide highly substituted β-lactones is described. Reactions occur with excellent diastereo- and enantioselectivity. The organo cascade comprises two CC bond formations and one CO bond formation. Up to four contiguous stereogenic centers including two fully substituted stereocenters are formed in the cascade.

N‐Heterocyclic Carbene Catalysis as a Tool for Gaining Access to the 3,4‐Dihydropyran‐2‐one Skeleton

AbstractAn overview of the progress made in the synthesis of 3,4‐dihydropyran‐2‐ones since the development of NHC catalysis is reported. Two distinct classes of species – electrophilic α,β‐unsaturated acylazolium and nucleophilic azolium enol/enolate intermediates – can easily be produced from different substrates through the intermediacy of NHC catalysis. They enable the construction of the 3,4‐dihydropyran‐2‐one skeleton, the core of natural and synthetic products with significant biological activities, through Michael additions, cycloadditions and rearrangements.

Catalyst selective and regiodivergent O- to C- or N-carboxyl transfer of pyrazolyl carbonates: synthetic and computational studies

The regiodivergent O- to C- or N-carboxyl transfer of pyrazolyl carbonates is described, with DMAP giving preferential N-carboxylation and triazolinylidenes promoting selective C-carboxylation (both with up to >99 : 1 regioselectivity). An enantioselective O- to C-carboxyl variant using NHC catalysis is demonstrated (up to 92% ee), while mechanistic and DFT studies outline the pathways operative in this system and provide insight into the reasons for the observed selectivity.

Direct Allylation of In Situ Generated Aldehyde Acyl Anions by Synergistic NHC and Palladium Catalysis

AbstractThe direct regioselective allylation of in situ generated aldehyde acyl anions has been achieved by synergistic NHC and Pd catalysis. It provides an efficient access to valuable β,γ‐unsaturated ketones under mild reaction conditions starting from easily accessible allylic carbonates and aldehydes without any preactivation. The synergistic catalysis method demonstrated herein adds a new dimension to the area of metal‐mediated C allylation.

Direct allylation of in situ generated aldehyde acyl anions by synergistic NHC and palladium catalysis.

The direct regioselective allylation of in situ generated aldehyde acyl anions has been achieved by synergistic NHC and Pd catalysis. It provides an efficient access to valuable β,γ-unsaturated ketones under mild reaction conditions starting from easily accessible allylic carbonates and aldehydes without any preactivation. The synergistic catalysis method demonstrated herein adds a new dimension to the area of metal-mediated C allylation.

ChemInform Abstract: Acyl Anion Free N‐Heterocyclic Carbene Organocatalysis

AbstractReview: 50 refs.

Direct β‐Activation of Saturated Aldehydes to Formal Michael Acceptors through Oxidative NHC Catalysis

Direct β‐Activation of Saturated Aldehydes to Formal Michael Acceptors through Oxidative NHC Catalysis

Direct β‐Activation of Saturated Aldehydes to Formal Michael Acceptors through Oxidative NHC Catalysis

Direct β‐Activation of Saturated Aldehydes to Formal Michael Acceptors through Oxidative NHC Catalysis

SNAr-Derived Decomposition By-products Involving Pentafluorophenyl Triazolium Carbenes

Pentafluorophenyl triazolium carbenes, widely used in NHC-catalysis, can decompose by several mechanisms. Under high concentration conditions, the azolium may undergo a pentafluorophenyl exchange by a proposed SNAr mechanism to give an inactive salt. In the presence of appropriate substrates, cyclization on the ortho-position of the arene can occur, also by SNAr. These adducts provide a potential pathway for catalyst decomposition and serve as a caveat to the development of new reactions and catalysts.

N‐Heterocyclic Carbene Catalyzed [4+2] Cycloaddition of Nitroalkenes with Oxodienes

NHC catalysis: N-heterocyclic carbenes were found to be efficient catalysts for the unprecedented [4+2] cycloaddition of nitroalkenes and oxodienes, giving the corresponding dihydropyrans in good yield with good diastereoselectivity (see scheme). Deuteration experiment reveals that the reaction is possibly initiated by the addition of N-heterocylic carbene to nitroalkenes.

NHC-catalysed annulation of enals to ene-1,4-diones: stereoselective synthesis of 1,3-diaryl-4-acyl cyclopentenes

Homoenolates generated from enals by NHC catalysis undergo annulation with ene-1,4-diones to afford acyl cyclopentenes stereoselectively.

Acyl anion free N-heterocyclic carbene organocatalysis

Reaction discovery using N-heterocyclic carbene organocatalysis has been dominated by the chemistry of acyl anion equivalents. Recent studies demonstrate that NHCs are far more diverse catalysts, with a variety of reactions discovered that proceed without acyl anion equivalent formation. In this tutorial review selected examples of acyl anion free NHC catalysis using carbonyl compounds are presented.

ChemInform Abstract: Oxidative γ‐Addition of Enals to Trifluoromethyl Ketones: Enantioselectivity Control via Lewis Acid/N‐Heterocyclic Carbene Cooperative Catalysis.

AbstractFor the first time Sc‐based Lewis‐acids have found to be effective in cooperative NHC catalysis for the enantioselective control in the title reaction.

Merging N-Heterocyclic Carbene and Photoredox Catalysis

Key words NHC catalysis - photoredox catalysis - tertiary amines - aldehydes

Organocatalytic Conversion of Ribose and Other Protected Carbohydrate Derivatives into 2-Deoxy-lactones

We report the simultaneous reduction of the 2-position and oxidationof the anomeric position in several protected furanosyl and pyranosylsugar derivatives, mediated through NHC catalysis. This reactionallows the one-step access to highly valuable 2-deoxy-sugars fromabundant 2-oxygenated sugar derivatives.