NHC-copper complexes

The hydrosilylation of carbonyl compounds by EtjSiH catalysed by the copper NHC complexes 65 and 66-67 constitutes a convenient method for the direct synthesis of silyl-protected alcohols (silyl ethers). The catalysts can be generated in situ from the corresponding imidazolium salts, base and CuCl or [Cu(MeCN) ]X", respectively. The catalytic reactions usually occur at room tanperature in THE with very good conversions and exhibit good functional group tolerance. Complex 66, which is more active than 65, allows the reactions to be run under lower silane loadings and is preferred for the hydrosilylation of hindered ketones. The wide scope of application of the copper catalyst [dialkyl-, arylalkyl-ketones, aldehydes (even enoUsable) and esters] is evident from some examples compiled in Table 2.3 [51-53],... 

Scheme 2.11 Hydroboration of arylalkenes catalysed by copper NHC complexes...

Remarkably, the B(pin) moiety can be introduced at the p- rather than at the a-site (vide supra) of a styrene or styrene-like substrate using a nonracemic copper-NHC complex, derived from 89d, in variable overall yields (51-98%). The reactions are run in THF at -50 °C over 48 hours in the presence of MeOH (2 equiv). The same B2Pin2 + CuCl + KO-t-Bu combination is used to generate the active Cu-B species. 

In the same context of enantioselective hydroborations, Lee and Hoveyda reported in 2009 the fimctionalization of nonactivated cyclic alkenes with the use of copper-NHC complexes (Scheme 3.66) [95]. In addition, asymmetric hydrobo-ration of two cyclic olefins proceeded with good enantioselectivities (72 and 89% ee s) in the presence of a catalytic amount of monodentate NHC 104 and CuCL... 

The stoichiometric insertion of terminal alkenes into the Cu-B bond of the (NHC)Cu-B(cat) complex, and the isolation and full characterisation of the p-boryl-alkyl-copper (I) complex has been reported. The alkyl complex decomposes at higher temperatures by P-H elimination to vinylboronate ester [67]. These data provide experimental evidence for a mechanism involving insertion of alkenes into Cu-boryl bonds, and establish a versatile and inexpensive catalytic system of wide scope for the diboration of alkenes and alkynes based on copper. 

The proposed reaction mechanism involves intermolecular nucleophilic addition of the amido ligand to the olefin to produce a zwitterionic intermediate, followed by proton transfer to form a new copper amido complex. Reaction with additional amine (presnmably via coordination to Cn) yields the hydroamination prodnct and regenerates the original copper catalyst (Scheme 2.15). In addition to the NHC complexes 94 and 95, copper amido complexes with the chelating diphosphine l,2-bis-(di-tert-bntylphosphino)-ethane also catalyse the reaction [81, 82]. 

Copper(I) complexes containing NHC-phenoxyimine 153 or NHC-phenoxyamine 154 were shown to be good catalyst systems for nitrene addition to alkenes 144 (Scheme 5.40) [45]. The catalyst systems showed to be highly efficient as only 1 mol% catalyst loading was required to afford aziridines 155 in moderate to good yields. 

Finally, NHC complexes of copper, formed in situ from the hnidazolium salt and CuBr have been used in the monoarylation of aniline [167]. Trinuclear Cu(I) catalysts have been applied to the arylation of pyrazoles, triazoles, amides and phenols [168] (Scheme 6.50). 

Ruthenium(II)-NHC systems ean be used for atom transfer radical polymerization (ATRP). Generally, similar results as for the analogous phosphine complexes are obtained. For the ATRP of styrene and methyl methacrylate (MMA) [(NHC)2peBr2] was found to rival copper(I)-based systems and to yield poly (MMA) with low polydispersities. Polymerizations based on olefin metathesis that are catalyzed by ruthenium-NHC complexes are discussed separately vide supra). 

The reactivity of dioxygen with nitrogen-coordinated copper(I) complexes has received extensive attention over the past two decades [53,54]. To date, analogous reactivity has not been realized for NHC-coordinated Cu(I). Ster-ically unhindered bis-carbene complexes of Cu(I) undergo rapid conversion to the corresponding ureas upon exposure to air in CH2CI2 solution (Eq. 4) [55]. This result suggests NHCs may not be universally applicable to metal-mediated oxidation chemistry. 

Raubenheimer et al. have developed a third route for transition metal NHC complexes with thiazol-2-ylidene, benzothiazol-2-yUdene and even isothiazol-5-ylidene ligands [45 9]. This method uses a thiazolyl transfer from lithium to a transition metal with subsequent protonation [47,49-54] or alkylation [41,45,46,48,51-56] of the nitrogen atom to generate the transition metal NHC complex. In this way, carbene complexes of copper(I)... 

Lipshutz and coworkers have developed copper hydride complexes with diphosphine ligands that catalyze the asymmetric hydrosilylation of aryl ketones at low temperatures (-50 to -78 °C) [68]. Nolan and coworkers discovered that copper complexes with NHC ligands are very efficient catalysts for the hydrosilylation of ketones, including hindered ketones such as di-cyclohexyl ketone and di-tert-butyl ketone [69]. 

Stabilized Cu(I) in the form of its iV-heterocyclic carbene (NHC) complex, e.g., (SIMes)CuBr (SIMes = iV,7V -f>is(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene), and the eyclohexyl analog [(ICy)2Cu]PF6, catalyzes click reactions very well in aqueous /-butanol, and even better in water alone. Low conversions were noted in nonaqueous solvents such as tetrahydrofuran (THF), /-BuOH, and dichloromethane (DCM). Starting from an alkyl bromide, triazoles could be smoothly generated by m situ conversion to the corresponding azide (aqueous NaNs) followed by copper-catalyzed cycloaddition. This is but one example of the potential for combining several steps in a single flask that culminates with a click reaction vide infra). The... 

The roles of NHC complexes of copper, silver, and gold in conjugate additions, allylic alkylations, reduction, boration, hydrofunctionalizations, hydrations, cross-couplings, and enyne cycloisomerization have been discussed. ... 

Chiral NHC-copper(I) complex (14) has been shown to catalyse the allylic arylation of allylic bromide with arylmagnesium bromides with an excellent y-selectivity. The 0 high regioselectivity is nicely complemented by very high enantioselectivities. 

Several Cu(I) complexes with N-heterocyclic carbene ligands have been described as CuAAC catalysts at elevated temperature in organic solvents, under heterogeneous aqueous conditions (when both reactants are not soluble in water), and under neat conditions [75]. These catalyst show high activity under the solvent-free conditions, achieving turnover numbers as high as 20 000. However, their activity in solution-phase reactions is significantly lower than that of other catalytic systems (for example, a stoichiometric reaction of the isolated copper(I) acetylide/NHC complex with benzhydryl azide required 12 h to obtain 65% yield of the product [76], whereas under standard solution conditions even a catalytic reaction would proceed to completion within 1 h). 

In the same year, Roland and coworkers described a chiral silver-NHC complex with a tert-butyl substituted backbone for copper-catalyzed addition of Et2Zn to 2-cyclohexanone. However, the addition product was isolated in low enantioselectivity (23% ee) [77]. Later on, Alexakis et al. modified the carbene structure to improve the enantioselectivity (Scheme 3.51) [78]. By using the chiral silver-NHC salt 90 to transmetallate and generate the Cu catalyst, the asymmetric conjugate addition of diethylzinc to 2-cycloheptanone was achieved in good yield (95%) and enantioselectivity (93% ee). 

In 2010, McQuade and coworkers described the application of complex 98 in the enantioselective conjugate borylation of acyclic a,p-unsaturated esters (Scheme 3.62) [91]. The copper(I) complex 98 exhibited excellent reactivities (88-95% yields) and enantioselectivities (82-96% ee) for p-borylation of a variety of aliphatic and aromatic a,p-unsaturated esters by using 1 mol% of 98. As typical in NHC-Cu(I)-catalyzed borylation reaction, methanol was a necessary additive in this transformation. The system was highly reactive and catalyst loadings... 

The apoptosis of the cells was clearly induced by the NHC-copper(I) complex. From these results, the NHC-copper(I) complexes showed that their biological behavior can compete with other NHC-metal-based complexes as well as cisplatin. 

Sadighi and coworkers were the first to report the reactivity of NHC-copper boryl complexes for the reduction of CO2 to CO [39]. Later, DFT studies imder-taken by Marder and coworkers showed that the reduction occmred through CO2 insertion into the Cu—B bond to give Cu-C02-boryl species [40]. Subsequent boryl migration from C to O allowed the release of CO. Importantly, CO2 insertion also occurred in NHC-copper alkyl systems. However, the energy barrier does not favor the migration and the CO elimination. 

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