Carbenes free N-heterocyclic

For many years, carbenes seemed to be elusive compounds and their isolation appeared impossible. Therefore, the first isolation and characterization of a free N-heterocyclic carbene (NHC) in 1991 marked a true... 

Scheme 1.9 Free N-heterocyclic carbenes via deprotonation or by reductive desulfurization.

The search for even more active and recyclable ruthenium-based metathesis catalysts has recently led to the development of phosphine-free complexes by combining the concept of ligation with N-heterocyclic carbenes and benzyli-denes bearing a coordinating isopropoxy ligand. The latter was exemplified for Hoveyda s monophosphine complex 13 in Scheme 5 [12]. Pioneering studies in this field have been conducted by the groups of Hoveyda [49a] and Blechert [49b], who described the phosphine-free precatalyst 71a. Compound 71a is prepared either from 56d [49a] or from 13 [49b], as illustrated in Scheme 16. 

By contrast, much of the work performed using ruthenium-based catalysts has employed well-defined complexes. These have mostly been studied in the ATRP of MMA, and include complexes (158)-(165).400-405 Recent studies with (158) have shown the importance of amine additives which afford faster, more controlled polymerization.406 A fast polymerization has also been reported with a dimethylaminoindenyl analog of (161).407 The Grubbs-type metathesis initiator (165) polymerizes MMA without the need for an organic initiator, and may therefore be used to prepare block copolymers of MMA and 1,5-cyclooctadiene.405 Hydrogenation of this product yields PE-b-PMMA. N-heterocyclic carbene analogs of (164) have also been used to catalyze the free radical polymerization of both MMA and styrene.408... 

N-Heterocyclic carbenes are an example of a family of nucleophilic catalysts [84-87]. For instance, the polymerization of p-butyrolactone was catalyzed by l,3,4-triphenyl-4,5-dihydro-l//,l,2-triazol-5-ylidene in the presence of methanol as an initiator [86]. This reaction was carried out in toluene at 80 °C. Nevertheless, an undesired elimination (Fig. 4) reaction was observed and control of the polymerization was lost. This issue was overcome by using ferf-butanol as a co-solvent, which reacts reversibly with the free carbene to form a new adduct. Owing to the decrease in the concentration of the free carbene, the elimination is disfavored and the polymerization is then under control provided that a degree of polymerization below 200 is targeted. As a rule, the reactivity of N-heterocyclic carbenes depends on their substituents. Hindered N-heterocyclic carbenes turned out to be not nucleophilic enough for the ROP of sCL. Recently, it was shown that unencumbered N-heterocyclic carbenes were more efficient catalysts [87]. 

Interestingly, Hedrick and coworkers reported a metal-free approach for the synthesis of star-shaped copolymers. They synthesized star-shaped PCLs by the ROP of eCL initiated by polyols in the presence of unencumbered N-heterocyclic carbenes [87]. 

N-Heterocyclic carbenes form intriguingly stable bonds with the majority of metals [12,21,29]. Whereas for saturated and unsaturated N-heterocyclic carbenes of comparable steric demand very similar bond dissociation energies have been observed, phosphines generally form much weaker bonds (Table 2) [21]. As a result, the equilibrium between the free carbene and the carbene metal complex lies far more on the side of the complex than... 

Abstract The manuscript describes the methods that are most often used in the preparation of N-heterocyclic carbene (NHC) complexes. These methods include (1) insertion of a metal into the C = C bond of bis(imidazolidin-2-ylidene) olefins (2) use of carbene adducts or protected forms of free NHC carbenes (3) use of preformed, isolated free carbenes (4) deprotonation of an azolium salt with a base (5) transmetallation from an Ag-NHC complex prepared from direct reaction of an imidazolium precursor and Ag20 and (6) oxidative addition via activation of the C2 - X (X = Me, halogen, H) of an imidazolium cation. 

The combination of the Herrmann s carbene ligand 58 and the Gade s NHC family 66 resulted in a new chiral N-heterocyclic carbene 69 (Scheme 47) [ 127]. The coupling strategy allows the free combination of oxazoline substituents in... 

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. 

Figure 2 Comparing free energy barriers to hydride transfer from ruthenium to acetophenone for neutral and cationic N-heterocyclic carbene ruthenium catalysts...

In 2006, Sames demonstrated that the valuable N-2-(trimethylsilyl) ethoxymethyl (SEM)-indoles (that can easily be deprotected to give the NH-free product) could also be selectively C2-arylated (Scheme 13, 06OL1979). Optimized conditions involving the use of a bulky and electron-rich palladium complex of N-heterocyclic carbene and phosphine allowed the arylation of a range of functionalized SEM-protected indoles in good-to-moderate yields. 

A range of metal-free organocatalysts have been used to good effect in the kinetic resolution of alcohols. A number of enantiomerically pure 4-aminopyridine-based catalysts effect kinetic resolution with high S values. These include the conforma-tionallyrestricted2,3-dihydroimidazo[l,2-a]pyridine (12.98) and the atropiso-meric catalyst (12.99). N-heterocyclic carbenes also function as nucleophilic... 

By using an N-heterocyclic carbene catalyst bearing a hydroxyl moiety, the Ma group reported an asymmetric cyclization of aryl 3-bromoenals and isatins. A series of chiral spirooxindole butenolides, including an alkenyl-substituted compound, were produced in excellent yields and enan-tioselectivity (up to 99% yield, 92% ee). The authors demonstrated that the hydrogen bonding between the free hydroxyl group of the catalyst and the isatin substrates would enhance the reactivity and selectivity. However, the Cs ion may also be involved as a Lewis acid to facilitate this transformation (Scheme 7.44). 

N-Heterocyclic carbene complexes can be generated from the stable, free carbenes or by reaction of carbene precursors. Three examples of the s)mthesis of N-heterocyclic carbene complexes from carbene precursors are shown in Equations 13.14-13.16. The reaction of an imidazolium salt with a complex containing a basic ligand forms N-heterocydic carbene complexes (Equation 13.14), as does transfer of the carbene from a silver-carbene complex (Equation 13.15), - or reaction of an imidazolium-2-carboxylate, with accompanying decarboxylation (Equation 13.16). ... 

Dihydroimidazolium carbene precursors or "saturated N-heterocyclic carbene" precursors are generated by a related sequence that includes reaction of a diamine, often generated by reduction of the glyoxaldimine, with triethylorthoformate, in the presence of acid. This reaction generates the dihydroimidazolium salts, wliich can be deprotonated to form the free carbene or used directly in the synthesis of carbene complexes. Finally, the acid-catalyzed reaction of the diamine with formaldehyde, followed by iodine and base, generates the free carbene. The silver complexes are typically generated by reaction of the protonated carbenes with Ag O. ... 

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