Imidazolium-based NHCs

In 2007, Tandukar and Sen reported the synthesis of a series of imidazolium-based (NHC)-Pd complexes that had been immobilized on 10 nm silica nanoparticles [40]. Complex 29 was the most active in the series, being able to couple u-butyl acrylate to a nimiber of iodo-aryls with excellent yields. 

Olefin dimerisation with Ni-NHC complexes became a topic of interest following reports of Ni(II) phosphine complexes being employed in imidazolium-based ionic liquid solvents [23, 24]. It had previonsly been established that aIkyl-Ni(II) complexes containing NHC ligands can rapidly decompose via imidazolium formation (Scheme 4.1) [5], and it was thus of interest to explore the effect that an excess of the imidazolinm cation would have on this reaction. 

Among these in situ protocols are those using ionic liquids as the solvent, or as both the solvent and the ligand. It was shown that the use of PdCOAc) in imidazolium-based ionic liquids forms in situ NHC-Pd(II) species [42], The use of methylene-bridged bis-imidazolium salt ionic liquids to form chelated complexes has also been reported [43], although better results have been obtained when Bu NBr is used as the solvent [44] and imidazolium salts were added together with PdCl in catalytic amounts [45]. Other related catalytic species such as bis-NHC complexes of silica-hybrid materials have been tested as recyclable catalysts [46,47]. 

Of course, the opposite has also been observed whereby an imidazolium salt oxidatively adds to a transition metal complex. [135,136]. This was first noticed in catalytic reactions involving transition metal phosphane complexes as catalysts and imidazolium based ionic liquids. Unexpected improvements in catalytic performance prompted investigations to find out whether the phosphane ligands had been replaced by more electron-rich NHC... 

With the current excitement that is being generated by the, so-called, N-heterocycUc carbenes (NHCs, imidazolylidenes) [9], reports of imidazolium-based ionic liquids being used to prepare metal imidazolylidene complexes are starting to appear [10]. The first came from Xiao et al, who prepared bis(imidazolylidene)palladium(ii) dibromide in [BMIMjBr [11]. All four possible conformers were formed (Scheme 6.1-3). 

The low volatility of ionic liquids and the easy separation of catalysts (which usually remain in these polar media) have made ionic liquids an interesting alternative to typically used organic solvents. Rather unsatisfactory results have been obtained in both copper-mediated [36] and copper-free [37] Sonogashira reactions, with aryl iodides being the only aromatic electrophiles coupled at reaction temperatures between 60 and 80 °C. It should further be noted that imidazolium-based ionic liquids are not necessarily innocent solvents, but can be deprotonated in the presence of bases to generate N-heterocycUc carbenes (NHCs). 

This reactivity was found not to be confined to Pd -complexes. Indeed, addition of methyl iodide to a solution of a [Ni°(NHC)2] complex at very low temperature initially yielded the desired [Ni°I(Me)(NHC)2]-lype complex, which then rapidly decomposed to form a C2-methylated imidazolium salt (Fig. 2). Studies on Ni-NHC catalysed alkene dimer-isation also illustrated the formation of C2-allq lated imidazolium salts. However, since these reactions were performed in imidazolium-based ionic liquids, rapid reformation of the active catalyst via oxidative... 

Welton and co-workers reported a detailed study of the Suzuki reaction performed in imidazolium ionic liquids using palladium phosphine based catalysts, and found that mixed phosphine-NHC palladium complexes of the formula [(IBuMe)Pd(PPh3)2X] were formed. All catalytic conditions leading to formation of these complexes were successful in affecting the Suzuki reaction, and those conditions in which they could not be detected showed no conversion. This strongly suggests that [(NHC)Pd] complexes are relevant to reactions run in imidazolium-based ionic liquids. 

Due to the ability of imidazolium compounds to form metallic Af-heterocyclic carbene complexes, imidazolium-based ionosilicas have widely been studied for the formation of silica-supported NHC species and found wide applications in organometallic catalysis. However, ionic species recently found to promote a large variety of reactions due to their ionic nature. Cooperative nucleophilic-electrophilic activation is a widely accepted concept in catalysis, and due to their ionic nature, ionic liquid should be considered as bifunctional catalysts. 

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 use of stoichiometric ruthenium-NHC complexes generated in situ from [Ruljd-COCKp-cymene)], an imidazohnm salt [4] or an imidizol(idin)ium-2-carboxylate [4] has been applied in the cyclopropanation of styrene 5 with ethyl diazoacetate (EDA) 6 (Scheme 5.2). No base was necessary when imidazolium-2 carboxylate were employed. The diastereoselectivity was low and the cis/trans ratio was around 50/50 (Table 5.1). Although the diastereoselectivity was moderate, the reaction was highly chemoselectivity as possible side reactions (homologation, dimerisation and metathesis) were totally or partially suppressed. 

Madsen and co-workers have reported an important extension to the amine alkylation chemistry, in which oxidation takes place to give the amide product [13]. A ruthenium NHC complex is formed in situ by the reaction of [RuCl Ccod)] with a phosphine and an imidazolium salt in the presence of base. Rather than returning the borrowed hydrogen, the catalyst expels two equivalents of H. For example, alcohol 31 and benzylamine 27 undergo an oxidative coupling to give amide 32 in good isolated yield (Scheme 11.7). 

In the presence of an imidazolium salt and a base, oxidative cyclization of a Ni(0) species upon the diene and an aldehyde takes place first and forms an oxanickellacycle 25, which equilibrates with a seven-membered oxanickella-cycle 26, naturally possessing a cis double bond. cr-Bond metathesis through 26 with hydrosilane affords (Z)-allylsilane (Z)-23. The role of NHC ligand (AT-heterocyclic carbene, generated by H+ elimination from imidazolium C2H by a base) is not clear at present a Ni(0)-NHC complex is believed to effectively produce 26. 

The chelate effect also favors oxidative addition of the C2—H bonds of imidazo-lium salts because it provides stabilized complexes. The reaction of a pyridine-imidazolium salt with [lrCl(cod)]2 yields the oxidative addition product, even in the absence of a base (Scheme 3.9), thus confirming that the oxidative addition of an imidazolium salt should be considered as a vahd process for the preparation of NHC—M—H complexes [24]. 

The broader subject of the interaction of stable carbenes with main-group compounds has recently been reviewed. Accordingly, the following discussion focuses on metallic elements of the s and p blocks. Dimeric NHC-alkali adducts have been characterized for lithium, sodium, and potassium. For imidazolin-2-ylidenes, alkoxy-bridged lithium dimer 20 and a lithium-cyclopentadienyl derivative 21 have been reported. For tetrahydropyrimid-2-ylidenes, amido-bridged dimers 22 have been characterized for lithium, sodium, and potassium. Since one of the synthetic approaches to stable NHCs involves the deprotonation of imidazolium cations with alkali metal bases, the interactions of alkali metal cations with NHCs are considered to be important for understanding the solution behavior of NHCs. 

Loosely bound fj -cyclopentadienyl anions can also serve as the base to deproto-nate imidazolium salts. When chromocene is reacted with an imidazolium chloride in THF the metal precursor loses one molecule of cyclopentadiene to form the 14-electron complex [( 7 -C5H5)Cr(NHC)Cl] [Eq. (13)]. This complex can be further oxidized by CHCI3 to give [( 7 -C5H5)Cr(NHC)Cl2]. This route also works with nickelocene to generate the corresponding [( -C5H5)Ni(NHC)Cl] complex. ... 

Triethylamine in THF can be used as the external base to deprotonate triazolium salts. The resulting NHCs were complexed in situ, e.g., to [(/7 -cymene)RuCl2]2, [(/ -cod)RhCl]2, and [(/ -C5Me5)RhCl2]2. Sodium carbonate in water/ DMSO deprotonates imidazolium iodides in the presence of mercury(II) dichloride to give [Hg(NHC)2][Hgl3Cl]. " A pyridine-functionalized imidazolium salt was deprotonated by lithium diisopropylamide (LDA) in THF and attached in situ to [(p -cod)Pd(Me)Br] [Eq.(17)]. After abstraction of the bromide anion with silver(I) a tetranuclear ring is formed. 

Metal complexes with M-heterocyclic carbene ligands were known long before the first stable NHCs were isolated. Wanzlick [5] and Ofele [6] demonstrated as early as 1968 that NHC complexes can be obtained by in situ deprotonation of azolium salts in the presence of a suitable metal complex without prior isolation of the free NHC ligand (Fig. 1). In these cases a ligand of the metal complex precursor (acetate or hydride) acted as a base for the deprotonation of the imidazolium cation. This method has been successfully transferred to other metal precursors containing basic ligands like [Pd(OAc)2] [97] and [(cod)lr(p-OR)2lr(cod)] [98, 99]. Alternatively, an external base such as NaOAc, KOf-Bu or MHMDS (M = Li, Na, K) can be added for the deprotonation of the azolium salt [100]. In general, the in situ deprotonation of azolium salts appears as the most attractive method for the preparation of NHC complexes as it does not require the isolation of the reactive free carbene or its enetetramine dimer. 

A new approach for the generation of NHCs has been reported using a cyclopentadi-ene(arene)iron complex (17).22 The method converts imidazolium to the free carbene in the presence of oxygen (peroxyradical anion is the base deprotonating the imidazolium salt). A colour change and precipitation of the oxidized iron complex are evidence for the reaction outcome. 

The NHC class of nucleophilic carbenes are also bases. The proton-deuteron exchange of NHCs attached to macromolecules has been studied and the influence of counterion has been explored.99 Substitution, both directly on the imidazolium unit and on the pre-orientating calixarene backbone, was also studied. The results showed that substitution of the imidazolium salts has a large influence on the H-D exchange rates in wet methanol. These results were presented as having implications for Suzuki coupling. 

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