Generation Of N-heterocyclic Carbenes Research Articles

Electrogenerated NHCs in Organic Synthesis: Ionic Liquids vs Organic Solvents Effects

AbstractIn the last twenty years, N‐heterocyclic carbenes (NHCs) have been extensively studied for their application as organocatalysts in stereoselective synthesis as well as ligands for transition metals‐promoted synthetic methodologies. Derived mainly from azolium salts, NHCs have demonstrated exceptional versatility in their generation usually performed by deprotonation or reduction (chemical or electrochemical). In particular, the generation of NHC under electrochemical conditions, starting from azolium‐based ionic liquids, has proven to be a successful green approach and demonstrated wide applicability in organic synthesis. In this Personal Account, the application of electrogenerated NHCs in organic synthesis will be discussed, with a particular attention to the different reactivity in ionic liquids compared to classical organic solvents.

Theoretical Insight towards Mechanism, Role of NHC and DBU in the Synthesis of Substituted Quinolines

AbstractA plausible mechanism for the conversion of aldimine to 2‐phenyl‐4‐difluoromethylquinoline catalyzed by N‐heterocyclic carbene (NHC) in association with 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) is investigated in detail by using density functional theory (DFT) method. Six significant stages are proposed to be involved in the whole catalytic cycle, starting from the generation of NHC followed by its nucleophilic interaction with the carbon atom of C‐N in aldimine to generate corresponding aza‐Breslow intermediate. This aza‐Breslow intermediate further undergoes intramolecular umpolung addition followed by several proton transfers to regenerate the NHC along with 2‐phenyl‐4‐difluoromethylquinoline. The role of NHC in this intramolecular umpolung addition of aza‐Breslow intermediate has been investigated by using conceptual DFT. Apart from NHC; the role of DBU in this catalytic cycle has also been monitored carefully. These theoretical findings are in good agreement with experimental results and also provide a deeper insight into the mechanism of NHC catalyzed synthesis of 2‐phenyl‐4‐difluoromethylquinoline.

Imidazolium Hydrogen Carbonates versus Imidazolium Carboxylates as Organic Precatalysts for N-Heterocyclic Carbene Catalyzed Reactions

Imidazolium-2-carboxylates (NHC-CO(2) adducts, 3) and (benz)imidazolium hydrogen carbonates ([NHC(H)][HCO(3)], 4) were independently employed as organic precatalysts for various molecular N-heterocyclic carbene (NHC) catalyzed reactions. NHC-CO(2) adducts were obtained by carboxylation in THF of related free NHCs (2), while the synthesis of [NHC(H)][HCO(3)] precursors was directly achieved by anion metathesis of imidazolium halides (1) using potassium hydrogen carbonate (KHCO(3)) in methanolic solution, without the need for the prior preparation of free carbenes. Thermogravimetric analysis (TGA) and TGA coupled with mass spectrometry (TGA-MS) of most [NHC(H)][HCO(3)] precursors 4 showed a degradation profile in stages, with either a concomitant or a stepwise release of H(2)O and CO(2), between 108 and 280 °C, depending on the nature of the azolium and substituents. In solution, NHC generation from both [NHC(H)][HCO(3)] salts and NHC-CO(2) adducts could be achieved at room temperature, most likely by a simple solvation effect. Both types of precursors proved efficient for organocatalyzed molecular reactions, including cyanosilylation, benzoin condensation, and transesterification reactions. The catalytic efficiencies of NHC-CO(2) adducts 3 were found to be approximately 3 times higher than those of their [NHC(H)][HCO(3)] counterparts 4.

Stereoselective Synthesis of 5-Substituted Pyrrolo[1,2-c]imidazol-3-ones: Access to Annulated Chiral Imidazol(in)ium Salts

A two-step synthesis of N-heterocyclic carbene (NHC) precatalysts by diastereoselective or enantioselective lithiation of pyrrolo[1,2-c]imidazol-3-ones followed by POCl(3)-induced salt formation is described. The resulting 3-chloro-pyrroloimidazol(in)ium salts may be coordinated to palladium(II) upon NHC generation with t-BuLi at low temperature. The method may facilitate exploitation of these compounds as chiral organocatalysts or ligands in metal catalysis.

Oxidative addition of 2-substituted azolium salts to Group-10 metal zero complexes—A DFT study

Generation of N-heterocyclic carbene (NHC) complexes [(dmpe)M(azol-2-ylidene)R] via the oxidative addition of a series of 2-substituted azolium salts to Group-10 zerovalent metal complexes has been investigated using density functional theory (2-R = H, Me, Ph; Azole = imidazole, thiazole, oxazole; M = Ni, Pd, Pt). Overall, platinum-based pathways result in the greatest enthalpies of reaction, but due to the reactive nature of Group-10 metals bearing the 1,2-bis(dimethylphosphino)ethane (dmpe) chelate, nickel and palladium species also have little trouble proceeding to stable products in the absence of a significant barrier. Imidazolium salts were found to be the most vulnerable to oxidative addition due to their low stabilisation energies when compared to the oxazolium and thiazolium species. Activation barriers show the general trend of phenyl > methyl > hydrido with regard to the azole 2-substituent, with no observed barrier for all but one of the 2-hydrido cases. Minimal barriers were found to exist in a number of cases for activation of a C(2)-CH3 bond suggesting that synthesis of alkyl-carbene complexes may be possible via this route under certain conditions, and therefore ionic liquids based on these substituted azolium salts may be active participants in catalytic reactions.

C−H Oxidative Addition of Bisimidazolium Salts to Iridium and Rhodium Complexes, and N-Heterocyclic Carbene Generation. A Combined Experimental and Theoretical Study

A series of bis-N-heterocyclic carbenes of rhodium and iridium have been obtained and characterized. The formation of the M−C bond has been studied according to experimental and theoretical data, showing that two different mechanisms are operative for the first (single proton deprotonation of the bisimidazolium salt, or oxidative addition followed by deprotonation of the metal hydride) and second (oxidative addition of the second bisimidazolium C−H bond, yielding a NHC-IrIII-H species) metalation processes. In the case of complexes with long linkers between the imidazolium rings, reductive elimination of HCl affords bisimidazolylidene complexes of IrI. According to the theoretical studies we concluded that thermodynamic parameters would determine the formation of the NHC-IrIII-H species, while IrI-NHC species would be kinetically favored in the case of complexes with long linkers between the azole rings. The crystal structures of a series of Ir-bis(NHC) complexes are described.

Generation of N-Heterocyclic Carbenes by Metal-Mediated Coupling of Propargylamine and Isocyanides

A new method for the synthesis of heterocyclic carbenes of imidazol-2-ylidene and oxazol-2-ylidene types implying a cycloaddition reaction of propargylamine and propargylic alcohol, respectively, to coordinated isocyanide ligands has been developed.