Nucleophilic heterocyclic carbene ligands

Fig. 6 Grubbs nickel complex bearing sterically encumbered nucleophilic heterocyclic carbene ligand...

Nielsen, D.J., CaveU, K.J., Skelton, B.W. and White, A.H. (2006) Methyl-palladium(U) complexes of pyridine-bridged bis(nucleophilic heterocyclic carbene) ligands substituent effects on structure, stabUity, and catalytic performance. Inorg. Chim. Acta, 359, 1855-69. 

The ease of formation of the carbene depends on the nucleophilicity of the anion associated with the imidazolium. For example, when Pd(OAc)2 is heated in the presence of [BMIM][Br], the formation of a mixture of Pd imidazolylidene complexes occurs. Palladium complexes have been shown to be active and stable catalysts for Heck and other C-C coupling reactions [34]. The highest activity and stability of palladium is observed in the ionic liquid [BMIM][Brj. Carbene complexes can be formed not only by deprotonation of the imidazolium cation but also by direct oxidative addition to metal(O) (Scheme 5.3-3). These heterocyclic carbene ligands can be functionalized with polar groups in order to increase their affinity for ionic liquids. While their donor properties can be compared to those of donor phosphines, they have the advantage over phosphines of being stable toward oxidation. 

Through the use of arenediazonium salts, the straightforward transformation of amines into cross-coupling products can be realized. Whenever the diazonium salts do not tolerate bases and strong nucleophiles (e.g., phosphines), base- and phosphine-free protocols have to be used. Heterocyclic carbene ligands serve well in cross-coupling of Aryl- and vinylboronic acids, or alkylboronates with arenediazonium salts.369,370 Several convenient phosphine-free protocols have been developed for the same purpose.371-373... 

Some of these approaches were attempted by Grubbs et al. 143 171. In later studies [45, 46], the phenoxyimine ligands used in their initial study were replaced with nucleophilic heterocyclic carbene (NHC) ligands with the objective of pushing more electrons into the metal center to reduce the tendency of a last-inserted acrylate... 

The use of functionalized isocyanides containing both the isocyanide function and the nucleophile in the same molecule leads to complexes with heterocyclic carbene ligands via a 1,2-addition across the C=N triple bond. Complexes with functionalized isocyanide ligands can be generated in template reactions or a nucleophile functionalized isocyanide can be reacted directly with a suitable metal complex. 

Generally, octatriene formation is favored by higher temperatures, higher phosphine and/or butadiene concentrations and, importantly, by an increase in steric bulk of either the ligand or the nucleophile. Indeed, Harkal et al. showed a selectivity switch from telomerization products to 1,3,7-octatriene formation by altering the steric demand of the /V-heterocyclic carbene ligand in the reaction of butadiene with isopropanol under further identical reaction conditions [48]. For the more basic nucleophiles, such as the alcohols, the telomer products are stable under experimental conditions, i.e. product formation is irreversible, but for more acidic substrates such as phenol, product formation is reversible and more 1,3,7-octatriene will be formed after the substrate has been depleted. 

The telomerization of dienes with alcohols as the nucleophile has now been conducted in a practical fashion. A palladium catalyst containing an N-heterocyclic carbene ligand has been shown to form linear dimeric ethers selectively from alcohols and butadiene with remarkably high turnover numbers (Equation 22.40). The activity of this catalyst is significantly higher than that of the more classical catalysts generated from Pd(OAc)j and PPhj. Under optimized conditions involving some added carbene precursor, presumably to... 

The surprising stability of N-heterocyclic carbenes was of interest to organometallic chemists who started to explore the metal complexes of these new ligands. The first examples of this class had been synthesized as early as 1968 by Wanzlick [9] and Ofele [10], only 4 years after the first Fischer-type carbene complex was synthesized [2,3] and 6 years before the first report of a Schrock-type carbene complex [11]. Once the N-heterocyclic ligands are attached to a metal they show a completely different reaction pattern compared to the electrophilic Fischer- and nucleophilic Schrock-type carbene complexes. 

AT-heterocyclic carbenes show a pure donor nature. Comparing them to other monodentate ligands such as phosphines and amines on several metal-carbonyl complexes showed the significantly increased donor capacity relative to phosphines, even to trialkylphosphines, while the 7r-acceptor capability of the NHCs is in the order of those of nitriles and pyridine [29]. This was used to synthesize the metathesis catalysts discussed in the next section. Experimental evidence comes from the fact that it has been shown for several metals that an exchange of phosphines versus NHCs proceeds rapidly and without the need of an excess quantity of the NHC. X-ray structures of the NHC complexes show exceptionally long metal-carbon bonds indicating a different type of bond compared to the Schrock-type carbene double bond. As a result, the reactivity of these NHC complexes is also unique. They are relatively resistant towards an attack by nucleophiles and electrophiles at the divalent carbon atom. 

The protocol of the allylic alkylation, which proceeds most likely via a c-allyl-Fe-intermediate, could be further improved by replacing the phosphine ligand with an M-heterocyclic carbene (NHC) (Scheme 21) [66]. The addition of a ferf-butyl-substituted NHC ligand 86 allowed for full conversion in the exact stoichiometric reaction between allyl carbonate and pronucleophile. Various C-nucleophiles were allylated in good to excellent regioselectivities conserving the 71 bond geometry of enantiomerically enriched ( )- and (Z)-carbonates 87. Even chirality and prochirality transfer was observed (Scheme 21) [67]. 

Recently, density functional calculations were performed to determine the nature and stereochemistry of the olefin insertion into the Cu-B bond of (NHC)Cu boryl complexes (NHC = iV-heterocyclic carbene). The theoretical calculations confirm that the mechanism of insertion involves a nucleophilic attack of the boryl ligand on the coordinated olefin. Furthermore, the hyperconjugation of Cu-C (bond angles, which was also experimentally confirmed by the X-ray diffraction studies of these boryl-copper complexes <2007OM2824>. 

Sato, Y., Yoshino, T., Mori, M. Pd-Catalyzed Allylic Substitution Using Nucleophilic N-Heterocyclic Carbene as a Ligand. Org. Lett. 2003, 5, 31-33. 

The majority of N-heterocyclic carbenes and their metal complexes are obtained from cyclic azolium derivatives (Fig. 8). Nevertheless, the first complex with a heteroatom stabilized carbene ligand, although it was not recognized as such, was prepared by Tschugajeff et al. as early as 1925 [157]. It was later identified as a heterocarbene complex [158]. Tschugajeff reacted the nucleophilic proton base... 

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. 

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