NHC-Cu complex

Fig. 2.10 Hydrosilylation catalysts of carbonyl compounds based on Cu-NHC complexes...

In a very recent combined experimental and computational study, Willans, Ariafard and co-workers also observed the formation of a bis(imidazolium) salt, although under quite markedly different conditions than those used by Albrecht and co-workers. During the attempted synthesis of a Cu -NHC complex derived from an asymmetric NHC ligand containing one mesityl and one 2-pyridyl N-substituent, via... 

Fig. 15 Formation of a 2-haloimidazolium salt via reaction of a Cu -NHC complex with an oxidant. ...

Fig. 16 Reaction of free NHC with Cu"-halide resulting in the formation of 1 1 mixtures of Cu -NHC complexes and 2-haloimidazolium salts. ...

NHC-silver species react readily, giving access to a large panel of NHC-metal complexes. However, the lack of stability and light sensitivity of silver complexes remain important drawbacks. The successful use of cationic Cu(NHC) complexes for transmetalation was first reported by Albrecht and coworkers, and copper appeared as an interesting alternative [98]. Under mild conditions, using [Ru(Cl)2(/ -cymene)]2, a new ruthenium(II) complex was prepared (Scheme 8.40). This procedure was a good alternative to the frequently used Ag(I)-NHC systems. 

MCRs Involving Cu-NHC Catalysts Cu-NHC complexes act as catalysts in a growing variety of reactions [107], Even more, the use of NHC ligands serve to protect Cu(I) from oxidation and disproportionation, thus enhancing its catalytic performances. In this section, some recent examples of Cu(I)-NHC species involved in MCRs are presented. 

Conjugate Borylation of a, p-unsaturated aldehydes. More challenging substrates for conjugate boryl addition are Q ,/9-unsaturated aldehydes, as 1,2-addition is competitive with the desired 1,4-addition. Fernandez and coworkers achieved the first Cu-catalyzed version of this reaction through the use of an alkoxy Cu-NHC complex under base-free conditions. The alkoxy Cu-NHC complex, as opposed to the chloride analog typically employed for this reaction class, was more catalytically active and chemoselective for the 1,4-addition. The alkoxy group... 

In yet another example of the utiUty of N-heterocyclie earbene hgands, the use of Cu-NHC complexes (e.g., 25) to catalyze the hydrosilation of hindered and functionalized ketones with Et3SiH was very recently described by Nolan and coworkers [Eq. (19)]/ Functionahties on the ketone substrate such as halide, ether and tertiary amine are well tolerated and excellent conversions are achievable using a number of variations of 25 (pre-synthesized or generated in situ) with different AT-substitution on the ring. 

In situ generated NHC-Cu-TEMPO complex 34 [eqn (12.3)] was explored in the aerobic oxidation of primary alcohols to the corresponding aldehydes. " Surprisingly, the addition of a base (potassium tert-butoxide, triethylamine) had a detrimental effect on the catalytic reaction using 34 as catalyst. This fact contrasted with other reported Cu-N-based ligands/TEMPO catalytic systems, in which the addition of base favored the reaction. The reaction proceeded more efficiently in chlorobenzene than in other solvents. Unexpectedly, [(NHC)CuX] complexes, prepared in situ from Cu powder and the corresponding imidazolium salt, or their simple combination with TEMPO, were completely inactive in the oxidation of alcohols. It was proposed that TEMPO anchored to Cu-NHC complexes facilitated the intramolecular proton abstraction, promoting the oxidation of alcohols. However, the mechanism was not further explored, and the relation between structure and activity of the catalyst remained unclear. 

In conclusion, copper-catalyzed hydroboration is a valuable synthetic tool for the access of enantiomerically enriched organoboranes. The easy accessibility and low cost of Cu-NHC complexes will certainly attract more investigation in this field and it is expected that the continued development of methodologies will contribute to other new applications associated with natural products. 

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],... 

The metal catalysed hydroboration and diboration of alkenes and alkynes (addition of H-B and B-B bonds, respectively) gives rise to alkyl- or alkenyl-boronate or diboronate esters, which are important intermediates for further catalytic transformations, or can be converted to useful organic compounds by established stoichiometric methodologies. The iyn-diboration of alkynes catalysed by Pt phosphine complexes is well-established [58]. However, in alkene diborations, challenging problems of chemo- and stereo-selectivity control stiU need to be solved, with the most successful current systems being based on Pt, Rh and An complexes [59-61]. There have been some recent advances in the area by using NHC complexes of Ir, Pd, Pt, Cu, Ag and Au as catalysts under mild conditions, which present important advantages in terms of activity and selectivity over the established catalysts. 

The complexes [Cu(NHC)(MeCN)][BF ], NHC = IPr, SIPr, IMes, catalyse the diboration of styrene with (Bcat) in high conversions (5 mol%, THF, rt or reflux). The (BcaO /styrene ratio has also an important effect on chemoselectivity (mono-versus di-substituted borylated species). Use of equimolecular ratios or excess of BCcat) results in the diborylated product, while higher alkene B(cat)j ratios lead selectively to mono-borylated species. Alkynes (phenylacetylene, diphenylacety-lene) are converted selectively (90-95%) to the c/x-di-borylated products under the same conditions. The mechanism of the reaction possibly involves a-bond metathetical reactions, but no oxidative addition at the copper. This mechanistic model was supported by DFT calculations [68]. 

Hydrothiolations (addition of H-SR across the CC multiple bond) of alkynes, electron-deficient aUcenes and electron-deficient vinyl arenes have been catalysed by NHC complexes of Ni and Cu, respectively [Scheme 2.17a-c],... 

The enantioselective P-borylation of a,P-unsaturated esters with (Bpin) was studied in the presence of various [CuCl(NHC)] or [Cu(MeCN)(NHC)] (NHC = chiral imidazol-2-ylidene or imidazolidin-2-ylidene) complexes. The reaction proceeds by heterolytic cleavage of the B-B bond of the (Bpin), followed by formation of Cu-boryl complexes which insert across the C=C bond of the unsaturated ester. Best yields and ee were observed with complex 144, featuring a non-C2 symmetric NHC ligand (Scheme 2.31) [114]. 

Fig. 4.15), are active for ATRP of both styrene and methylmethacrylate (MMA) [46]. Polymerisation was well controlled with polydispersities ranging from 1.05 to 1.47. The rates of polymerisation 1 x 10 s ) showed the complexes to be more active than phosphine and amine ligated Fe complexes, and were said to rival Cu-based ATRP systems. It was quite recent that Cu(I) complexes of NHCs were tested as ATRP catalysts [47]. In this work, tetrahydropyrimidine-based carbenes were employed to yield mono-carbene and di-carbene complexes 42 and 43 (Fig. 4.15), which were tested for MMA polymerisation. The mono-carbene complex 42 gave relatively high polydispersities (1.4-1.8) and a low initiation efficiency (0.5), both indicative of poor catalyst control. The di-carbene complex 43 led to nncontrolled radical polymerisation, which was ascribed to the insolubility of the complex. 

The NHCs have been used as ligands of different metal catalysts (i.e. copper, nickel, gold, cobalt, palladium, rhodium) in a wide range of cycloaddition reactions such as [4-1-2] (see Section 5.6), [3h-2], [2h-2h-2] and others. These NHC-metal catalysts have allowed reactions to occur at lower temperature and pressure. Furthermore, some NHC-TM catalysts even promote previously unknown reactions. One of the most popular reactions to generate 1,2,3-triazoles is the 1,3-dipolar Huisgen cycloaddition (reaction between azides and alkynes) [8]. Lately, this [3h-2] cycloaddition reaction has been aided by different [Cu(NHC)JX complexes [9]. The reactions between electron-rich, electron-poor and/or hindered alkynes 16 and azides 17 in the presence of low NHC-copper 18-20 loadings (in some cases even ppm amounts were used) afforded the 1,2,3-triazoles 21 regioselectively (Scheme 5.5 Table 5.2). 

Normally, copper-catalysed Huisgen cycloadditions work with terminal alkynes only. The formation of a Cu-acetylide complex is considered to be the starting point of the catalyst cycle. However, the NHC-Cu complex 18 was able to catalyse the [3-1-2] cycloaddition of azides 17 and 3-hexyne 23 (Scheme 5.6). 

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). 

Xia and co-workers synthesised a number of Pd-NHC complexes (33, 34, 36) for carbonylative Suzuki reactions (Fig. 9.6) [41], Various aryl iodides were carbonylatively coupled (P = 1 atm) with either phenylboronic acid or sodium tetraphenylborate. All the complexes were highly active, but 33 provided the best results with >76% selectivity for ketone in all the reactions. Xia followed this work with the double carbonylation of various aryl iodides with several secondary amines using the catalysts [CuX(Mes)] (37-X) and [Cu(IPr)X] (38-X) (X = I, Br, Cl) (3 MPa, 100°C, 10 h) (Scheme 9.7) [42],... 

Following this pnblication, the anthors tested a series of Pd-NHC complexes (33-36) for the oxidative carbonylation of amino compounds (Scheme 9.8) [44,45]. These complexes catalysed the oxidative carbonylation of amino compounds selectively to the nreas with good conversion and very high TOFs. Unlike the Cu-NHC catalyst 38-X, the palladium complexes catalysed the oxidative carbonylation of a variety of aromatic amines. For example, 35 converted d-Me-C H -NH, d-Cl-C H -NH, 2,4-Me3-C H3-NH3, 2,6-Me3-C H3-NH3, and 4-Ac-C H3-NH3 to the corresponding nreas with very high TOFs (>6000) in 1 h at 150°C, in 99%, 87%, 85%, 72%, and 60% isolated yields, respectively (Pco,o2 = 3.2/0.8 MPa). 

The metal-carbene bond distances in this family of complexes (2.082 (2) A for Ag, 1.9124 (16) A for Cu, and 2.035 (12) A for Au) are within the range of reported values for typical group 11 metal NHC complexes (23). The metal carbene units are almost linear, with a C-M-C bond angle of 178.56 (13)°, 177.70 (9)°, and 177.7 (6)° for Ag, Cu, and Au, respectively. The imidazole units for 2 -Ag, 2 -Cu, 2Me Au exhibit structural parameters typically observed for coordinated NHC ligands. There are no inter- or intramolecular metal-metal interactions in these complexes. 

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>. 

E is facile. Dehydrochlorination provides the aromatic products 233. An alternatively possible HC1 elimination/electrocyclization/decarboxylation pathway was excluded, since lactone 230B was thermally stable under the reaction conditions in the absence of the catalyst. (NHC)Cu(I) catalyst 232 gave comparable or better yields than 231 in these ATRC/ring contraction sequences, while other (NHC)Cu(I) complexes provided considerably lower yields [320]. Chlorinated cyclic compounds arising from ATRC can also be transformed to chlorinated furans [321]. 

Sometimes the Ag - NHC reagent has a twofold effect (i) transmetallation of the carbene and (ii) oxidation of the metal. The reaction of the dimetal-lic Ag biscarbene 43 with [ (p-cymene)RuCl2 h yields the Ru(II) complex 44 (Scheme 36). However, when the same complex 43 reacts with RuCl2(PPh3)3, a Ru(III) complex is obtained (45) with a CCO tripod coordination of the ligand [140]. In this latter case, the reduction of Ag(I) to Ag(0) is confirmed by the formation of a silver mirror in the reaction vessel. Compound 43 can also react with Cul to afford a square planar NHC - Cu(I) complex [141]. 

Owing to the lability of acetonitrile ligands, [Cu(MeCN)4]X (X = Pp6 or BF4) was found to be a convenient starting material for the synthesis of cationic NHC-Cu(I) complexes. In this case, the in situ formation of NHC from the corresponding chlorinated salts was found more suitable to isolate cationic biscarbene complexes [(NHC)2Cu]X. Reaction of Pd(II) precursor [PdCl2(PhCN)2] with one equivalent of IPr afforded the dimer [(IPr)PdCl]2. ... 

Guimoe recently demonstrated the addition of thiols to electron-deficient alkenes using well-defined Cu-NHC thiolate complexes (31) [255, 256]. The prehminary scope is broad, with a number of potentially reactive electron-withdrawing groups being well-tolerated. Both alkane thiols and arene thiols are effective. In addition, sterically hindered olefins also react efficiently. 

Equation 31 Thiolation of electron-deficient alkenes with Cu-NHC thiolate complexes [255]... 

A series of three phosphorescent mononuclear (NHC)-Cu(I) complexes has been investigated. Their photophysical properties were found to be largely controlled by NHC (N-heterocyclic carbenes) ligand chromo-phores. Modification of this ligand leads to emission colour tuning over 200 nm range, and emission quantum yields of 0.16-0.80 in the solid state. These complexes offer high quantum efficiencies, a short emission decay time, and tunable emission color. 

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... 

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