NHC-Cu catalyst

Nitrene addition to alkenes can be aided by the nse of a transition metal, such as copper, rhodium, ruthenium, iron, cobalt, etc. NHC-Cu catalysts have been used in nitrene addition. For example [Cu(DBM)(IPr)] 147 (DBM = dibenzoyl-methane) was successfully employed in the aziridination of aliphatic alkenes 144 in presence of trichloroethylsulfamate ester 145 and iodosobenzene 146 (Scheme 5.38) [43]. 

Copper as cheap metal was also applied in carbonylation reactions. In 2009 Xia and colleagues described a general and efficient copper-catalyzed double amino-carbonylation of aryl iodides (Scheme 2.46) [292], Using an NHC-Cu catalyst, aryl iodides were double carbonylated with amines in good yields (72-93 %). 

Polymer science is also an interesting axis of development and the Buch-meiser group recently investigated the immobilization of NHC-Cu catalysts on amphiphilic block-copolymer and their utilization in different hydrosilylation reactions. ... 

Following advances made in reduction reactions (vide supra), hydroboration and diboration have been the subject of intense investigation with NHC-Cu catalysts. Early work by Sadighi revealed that [(ICy)Cu(Ot-Bu)] efficiently catalyzed the 1,2-diboration of aldehydes. Mechanistic studies permitted to rationalize a number of features of this reaction and notably ruled out a possible oxidative addition pathway to favour c-activation of the diboron reagent by the copper centre. [(ICy)Cu(Ot-Bu)] was also used for the diaster-eoselective diboration—in fact, hydroboration after work-up—of sulfinyl aldimines. ... 

Finally, isolated reports on the ability of NHC-Cu complexes to catalyze diverse organic transformations can be found throughout the literature and notably include heterocycles synthesis, atom-transfer radical cyclization leading to chloronaphthalenes, and allylation reactions using [(IPr)CuFj and an allylsiloxane. An increasing number of studies involving the use of CO2 with NHC-Cu catalysts has also been reported lately, they encompass... 

Stable precursors, such as boranes and silanes, were also shown to display good reactivity in NHC-Cu-catalyzed conjugated additions. The groups of Ohmiya and Sawamura reported the copper-catalyzed 1,4-addition of alkyl-boranes to enones, respectively in a racemic and enantioselective version. Organosilanes, te. RSiFj or RSi(OR )3, can also be used with NHC-Cu catalysts in conjugate addition to enones and allylic epoxides. ... 

Hoveyda and co-workers reported that the regioselective hydroboration of terminal alkynes could be performed by using saturated NHC-Cu catalysts in combination with [B(pin)]2 and methanol as a proton source. The group of McQuade extended the scope of this transformation to internal allq nes. It was shown that a subtle match between the substrate and the catalyst was required... 

Hoveyda and co-workers also described the enantioselective hydroboration of styrene derivatives by NHC-Cu catalysts. Carboboration reactions of the same substrates were similarly performed. An electrophilic partner such as benzyl chloride or an in situ generated arylpalladium(ii) species could be used to react with the vinylcopper intermediate. 

Silylcupration reactions using NHC-Cu catalysts have only been studied recently. In the great majority of the cases studied, Suginome reagent PhMe2Si-B(pin) has been employed as a nucleophilic silicon source for the copper(i)-mediated transfer of a silicon moiety onto an electrophilic substrate. 

Figure 13.26 Bis-paracyclophane NHC ligand and [(NHC)Cu] catalyst for asymmetric hydrosilylation.

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). 

A number of Pd or Cu catalysts bearing NHC ligands have been prepared for carbonylation of aryl halides. Nacci and co-workers synthesised the benzothiazole carbene ligated Pd complex 32 (Fig. 9.6) and tested it for aryl halide carbonylation... 

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]. 

Readily available A -r-butanesulfinylimine derivatives of aldehydes react with B2piii2 in the presence of the NHC-copper catalyst (ICy)Cu-O-t-Bu (5 mol%) to give high ratios of diastereomeric a-amino boronate estersJ Benzene is the solvent of choice, as lower yields are observed for the reaction below, run in toluene (69%), THF (50%), or dioxane (62%). Both alkyl and aryl aldimines participate to give dr s >95 5. The utility of this highly diastereoselective process was demonstrated by its application to a synthesis of bortezomib (Velcade), a U.S. Food Drug Administration (FDA)-approved and clinically useful protease inhibitor. ... 

Li, P. H., Wang, L., and Zhang, Y. C. 2008. Si02-NHC-Cu(I) An efficient and reusable catalyst for [3-1-2] cycloaddition of organic azides and terminal alkynes under solvent-free reaction conditions at room temperature. Tetrahedron. 64(48) 10825-10830. 

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 silica-immobilized Cu(I)-NHC heterogeneous catalyst LI (Fig. 5.9) was also found to be active in this reaction. In this case, after the reaction, the catalyst was separated by simple filtration and could be reused directly without further purification up to six repetitive cycles [112]. 

M. Wang, P. Li, L. Wang, Eur. J. Org. Chem. 2008, 2255-2261. Silica-immobilized NHC-Cu(I) eomplex an efficient and reusable catalyst for A3-coupling (aldehydes-alkyne-amine) under solventless reaction conditions. 

DFT has been used to model the hydrosilylation of ketones catalysed by NHC-Cu(I) hydrides. Using CuF as pre-catalyst, a four-centre metathesis TS is identified. 

In 2011 Tomioka and co-workers expanded their previously reported Cu-catalysed asymmetric allylic arylation of aiyl Grignard reagent and cinnamyl bromides [33] to the corresponding aliphatic bromides [34]. For this purpose, structural steric and electronic modifications of their chiral Cu(I)-NHC Cl catalyst... 

The copper-NHC-catalysed addition of organoaluminium reagents to cyclo-hexenones and cycloheptenones reported by Hoveyda [58] is, in some cases, slightly less selective than those performed in the presence of phosphoramidites or phosphinamine catalysts (<90% ee for the imidazolium ligands versus <99% ee that the phosphoramidites and phosphinamine can provide). However, NHC-Cu catalysis provides better results (up to 97% ee and 97% conv) when challenging cyclopentenones and bulky p-substituted cycUc enones (bearing n-butyl, alkynyl, aryl or an ester group as the p substituent) are used as substrates (Scheme 25). 

Other computational studies involving NHC-Cu species considered the formation of phenylisocyanates from nitrobenzene, and the development of [3-1-2] cycloaddition reactions for the formation of 1,2,3-triazoles. In the latter case the use of NHCs allowed the direct use of copper(I) catalysts, whereas copper(II) precursors were predominant before. With [(NHQCuBrj the reaction could be run in water and was successful even for internal alkynes, an unusual observation as the intermediacy of Cu-acetylides had previously been assumed. Calculations showed that the [(SIMes)Cu] fragment was ideally set up to bind internal alkynes in an p -fashion and hence activate them towards cycloaddition. With terminal alkynes the acetylide route may still be operative. 

The use of NHC-Cu complexes in catalysis is still in its first decade but these catalysts have already reached a level of efficiency, notably in key C-C bond forming enantioselective reactions, which makes copper the leader of the Group 11 triad. In addition, NHC-Cu species have also shown impressive properties in other fields than catalysis (biochemistry, materials, making these compounds all the more appealing for further studies. 

Figure 18 Poly-NHC-Cu complexes employed as catalysts In C—N couplings.

Other computational studies involving NHC-Cu species considered the formation of phenylisocyanates from nitrobenzene, and the development of [3+2] cycloaddition reactions for the formation of 1,2,3-triazoles. In the latter case the use of NHCs allowed the direct use of copper(i) catalysts, whereas copper(ii) precursors were predominant before. With [(NHC)CuBr] the reaction could be run on water and was successful even for internal alkynes, an unusual observation because the intermediacy of Cu-acetylides had previously been assumed. Calculations showed that the [(SIMes)Cu] fragment was ideally set up to bind internal alkynes in an i] -fashion and hence activate them towards cycloaddition. With terminal alkynes the acetylide route may still be operative. Other computational studies on the catalytic activity of [(NHC)Cu] complexes in which the NHC has no particular role but to stabilize the metal by strong o-donation and offer steric protection have been reported, including the activation of CO2 by [(NHC)Cu(EPh3)] (E = Si, Ge, Sn) and the carboxylation of the C-H bond of heteroarenes. The barriers of the two steps of the catalytic cycle of the [(NHC)Cu ]-catalyzed hydrosilylation of ketones have been computed, yet it was shown that the nature of the NHC was not a controlling factor. While the barrier of the hydrocupration step is determined by the nature of the ketone, that of the o-bond metathesis step occurs mainly under electronic control. 

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