Synthesis of N-heterocyclic carbene

Recently, the reactivity (base, nucleophile, catalyst) and the role in modem organic synthesis of N-heterocyclic carbenes (cychc carbenes bearing at least one amino substituent) has been set-up by Ender et al. [60,61]. The possible utilization of NHCs as ligands for transition-metal catalyst [62,63] and as organocatalyst has been emphasized [61]. The inversion of the normal reactivity (umpolung) induced via NHCs has been extensively discussed. Classical carbon-carbon-bond-forming reactions (benzoin condensation, Stetter reaction, etc.) have been re-examined using ionic liquids as pre-catalysts in the presence of bases. 

Winkelmann OH, Navano O. Microwave-assisted synthesis of N-heterocyclic carbene-palladium(II) complexes. Adv Synth Catal. 2010 352 212-214. 

Landers B, Navarro O. Microwave-assisted synthesis of (N-heterocyclic carbene) Ni(Cp)Cl complexes. Inorg Chim Acta. 2012 380 350-353. 

Synthesis of N-heterocycles with participation of carbene complexes 91SL381. 

The isolation and structural characterization of aluminum hydroxides with terminal OH groups is a s)mthetic challenge, and efforts were made to prepare well-defined analogues of methylalumoxane (MAO). The strategy of hydrolysis of metal chlorides in the presence of a base to quench the hydrogen chloride generated during the reaction was adopted. This synthesis can be performed in two different ways (i) hydrolysis of a metal halide in a two-phase liquid NHs-toluene system in the presence of KOH and KH and (ii) hydrolysis of a metal halide in the presence of a stoichiometric amount of N-heterocyclic carbene. Both routes are reliable, but the latter one may prove to offer more versatility and be relatively easier to conceive. 

Other direct syntheses of halide free ionic liquids can be categorized into three groups (1) synthesis via N-heterocyclic carbene intermediates, (2) phosphorus based direct reactions with imidazoles and (3) sulfur-based direct reactions with imidazoles as discussed further below. 

The basic nature of N-heterocyclic carbenes, stabilized by the presence of two adjacent N atoms, has been emphasized by several authors [38], Therefore, the yield and the selectivity of any organic synthesis (driven by the reactivity of a substrate vs. appropriate bases and carried out in imidazohum salts as solvents) can be affected by side reactions related to the acidity of C2-H unit in 1,3-dialkylimidazo-lium cation and to the basicity and nucleophilicity of the resulting N-heterocychc carbene. On this subject, noticeable work (related to the Baylis-Hillman, Knoevenagel and Claisen condensation, Homer reaction, etc.) carried out in RTlLs has been reported and discussed [37]. 

Recently, the ability of N-heterocyclic carbenes to promote the Staudinger reaction has been investigated using ionic liquids, in the presence of suitable base as pre-catalysts. According to the procedure suggested by Smith et al., a solution of base (potassium hexamethyldisilazide KHMDS, toluene as solvent) was added to the suspension of ionic liquid (triazolium salt) in Et O and stirred under N. Subsequently, the mixture was added of diphenylketene and of imine and stirred at room temperature before concentration in vacuo (Scheme 16.6). The order of addition of reactants is critical for the success of the synthesis [95]. 

R320 D. P. Curran, A. Solovyev, M. M. Brahmi, L. Fensterbank, M. Malacria and E. Lacote, Synthesis and Reaction of N-Heterocyclic Carbene Boranes , Angew. Chem. Int. Ed., 2011, 50, 10294, S10294/1. 

Feroci M, Orsini M, Rossi L, Inesi A (2012) The double role of ionic liquids in electrooiganic synthesis green solvents and precursors of N-heterocyclic carbenes. CurrOig Synth 9 40-52... 

Reeds, J. R, Whitwood, A. C., Healy, M. R. Fairlamb, 1. J. S. (2013). Synthesis and reactivity of N-heterocyclic carbene gold(I) and gold(III) imidate complexes and their catalytic activity in 1,5-enyne cycloisomerization. Organometallics, 32,3108-3120. 

Decomposition reactions of N-heterocyclic carbenes are an important aspect of NHC chemistry that needs to be considered in the design, synthesis and application of NHC complexes. In many cases, the decomposition reactions involve species on the metal that are key intermediates in the catalytic cycle, and so the relative reactivity of the desired catalytic transformations versus the decomposition reaction must be assessed. It is important to note that reactions occurring under stoichiometric conditions may not mirror reactivity under catalytic conditions. In addition, some decomposition reactions are reversible. The reductive elimination of an NHC and hydride ligand is an example of this, as its... 

Synthesis, Activation, and Decomposition of N-Heterocyclic Carbene-Containing Complexes... 

The groups of Smith [14] and Ye [15] independently initiated the field of N-heterocyclic carbene (NHC) mediated ketene derived azolium enolate chemistry in 2007 through Staudinger-type -lactam synthesis. Ye employed... 

The focus of this chapter is the synthesis and medicinal applications of metal conq)lexes of N-heterocyclic carbenes (NHCs). Silver NHC conqplexes will be examined for their potential uses as antimicrobials and based... 

Synthesis of Chiral N-heterocyclic Carbenes and of Their Complexes... 

Zhang YR, He L, Wu X, Shao PL, Ye S (2008) Chiral N-heterocyclic carbene catalyzed Staudinger reaction of ketenes with imines highly enantioselective synthesis of W-Boc P-lactams. Org Lett 10 277-280... 

Synthesis and structural characterization of linear Au(l) N-heterocyclic carbene complexes New analogues of the Au(l) phosphine drug auranofin. Journal of OrganometaUic Chemistry, 690, 5625-5635. 

Further improvements in activity of the ruthenium carbene complexes were achieved by incorporation of methyl groups in 3,4-position of imidazol-2-ylidene moiety. Introduction of sulfur in the trara-position to the N-heterocyclic carbene leads to increased stability of the resulting ruthenium complexes. The synthesis and the first applications of these new rathenium complexes are described herein. 

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