Imidazolium salts reduction

In an attempt to increase the ionic liquid/hexane partition coefficient, a new salen ligand appended with an imidazolium salt was developed (Fig. 5) [18]. Unfortunately, modification of the ligand caused a dramatic reduction in the enantioselectivity - down to 57% ee at most - although the reasons for this behavior remain unclear. 

Palladium NHC systems for the hydrodehalogenation of aryl chlorides and bromides and polyhalogenated aromatic substrates originate from about the same time as the first reports on Ni chemistry, and show many similarities. Initial efforts showed that the combination of PdCdba) (2 mol%), one equivalent of imidazolium chloride and KOMe produced an effective system for the reduction of 4-chlorotolu-ene, especially upon use of SIMes HCl 2 (96% yield of toluene after 1 h at 100°C) [7]. Interestingly, higher ligand to metal ratios severely inhibited the catalysis with only 7% yield of toluene achieved in the same time in the presence of two equivalents of SIMes HCl 2. Variation of the metal source (Pd(OAc)2, Pd(CjHjCN)jClj), alkoxide (NaOMe, KO Bu, NaOH/ ec-BuOH) or imidazolium salt (IMes HCl 1, IPr HCl 3, lAd HCl, ICy HCl) all failed to give a more active catalyst. 

Reports of reductive elimination from early transition metals are uncommon. However, Bullock and co-workers have reported the elimination of IMes from [WCp(IMes)(CO)2][B(C Fj) J to form the 2-H-imidazolium salt, during ketone hydrogenation probably via a form of reductive elimination process [38]. 

While the reductive elimination is a major pathway for the deactivation of catalytically active NHC complexes [127, 128], it can also be utilized for selective transformations. Cavell et al. [135] described an interesting combination of oxidative addition and reductive elimination for the preparation of C2-alkylated imida-zohum salts. The in situ generated nickel catalyst [Ni(PPh3)2] oxidatively added the C2-H bond of an imidazolium salt to form a Ni hydrido complex. This complex reacts under alkene insertion into the Ni-H bond followed by reductive elimination of the 2-alkylimidazolium salt 39 (Fig. 14). Treatment of N-alkenyl functionalized azolium salts with [NiL2] (L = carbene or phosphine) resulted in the formation of five- and six-membered ring-fused azolium (type 40) and thiazolium salts [136, 137]. 

The carbene complexes can also be formed by direct oxidative addition of ze-rovalent metal to an ionic liquid. The oxidative addition of a C-H bond has been demonstrated by heating [MMIM]BF4 with Pt(PPh3)4 in THF, resulting in the formation of a stable cationic platinum carbene complex (Scheme 15) (189). An effective method to protect this carbene-metal-alkyl complex from reductive elimination is to perform the reaction with an imidazolium salt as a solvent. 

In spite of the successful use of NHCs in a number of palladium-catalyzed reactions, no system for hydrogenation was reported until 2005. This can be easily explained as it had been observed that hydridopalladium-carbene species decompose due to attack of the hydride on the carbene, which results in its reductive elimination to yield the corresponding imidazolium salt [ 190]. However, Cavell and co-workers recently showed that the oxidative addition of imidazolium salts to bis-carbenic palladium complexes leads to isolable NHC-hydridopalladium complexes [191]. This elegant work evidenced the remarkable stabilizing effect of NHC ligands in otherwise reactive species and led to the development of the first NHC-palladium catalyst for hydrogenation. 

Oxidative addition of C2 - H bonds of imidazolium salts to low valent metals was first observed by Nolan and coworkers in 2001, who proposed a NHC - Pd - H intermediate in the catalytic cycle of the dehalogenation of aryl halides with Pd(dba)2 in the presence of imidazolium salts [154]. More direct evidence of this process was described by Crabtree and coworkers two years later [155]. The reaction between a pyridine-imidazolium salt and Pd2(dba)3 afforded the preparation of bis-NHC - Pd(II) complexes by C2 - H oxidative addition (Scheme 40). The presumed Pd - H intermediates were not detected. The authors proposed a mechanism via two successive C - H oxidative additions followed by reductive elimination of H2 [ 155]. 

The C2 - H oxidative addition of imidazolium salts to metal complexes was recently proved for metals other than low valent group 10. The reaction of a ferrocenyl-bisimidazolium salt to [IrCl(cod)]2 in the presence of NEt3 provided the first evidence of the preparation of a stable NHC-Ir(III)-H complex by direct oxidative addition of the imidazolium salt [96]. It was proposed that the ferrocenyl fragment may be sterically protecting the M - H from further reductive elimination, but later it was shown that this fragment was not necessary in order to obtain the desired NHC-Ir(III)-H complexes (Scheme 43) [159]. The role of the weak base (NEt3 in this case) had to be reconsidered in order to explain the overall metallation process, and it was proposed that a mechanism as that shown in Scheme 44 may better explain the process. The oxidative addition of the C2 - H bond of the imida-... 

Hydrogen peroxide in acetic acid converts l-(arylamino)-l,3-dihydro-2H-imidazole-2-thiones 26 into 2-unsubstituted imidazoles 28 (an "oxidative reduction". Scheme 5) (98H929, 02TH). Alkylation at the unsubstituted ring nitrogen atom (3-N) of 28 furnishes imidazolium salts 29 (Scheme 5). 

Scheme 5 Oxidative reduction of thiones 26 and the conversion into imidazolium salts 29.

Figure 3.50 Synthesis of a chiral amino functionalised NHC ligand by reduction of a chiral imino functionalised imidazolium salt using NaBH. ...

Figure 3.89 Syntheses of a phosphino functionalised imidazolium salt using the silane reduction route.

Note Reaction of the dimethyl palladium(U) carbene complex with excess methyl iodide leads to decomposition of the compound by reductive elimination of an imidazolium salt that remains pendant on the phosphane anchor [283]. 

The decomposition of the dimethyl palladium(II) carbene complex with excess methyl iodide is a stepwise process. Although the authors [282] propose oxidative addition of methyl iodide on the palladium centre forming an octahedral palladium(IV) complex, it seems much more likely, with respect to the rarity of palladium(IV) compounds [284,285], that the first step is reductive elimination of an imidazolium salt, a decomposition pathway found to be fairly common after the initial publication of McGuinness et al. [283], Oxidative addition of methyl iodide followed by reductive elimination of ethane would account for the accumulation of iodide ligands on the palladium centre and a Pd(0)/Pd(II) redox couple. However, in the last step, a six coordinate Pd(IV) centre still seems to be necessary (see Figure 3.91). 

Our now familiar phosphino functionalised imidazolium salt - PhjPCHjCHjlmMes - has attracted further attention to warrant a third route for its synthesis. Nolan and cowoikers used arylimidazole, dibromoethane and KPPh and obtained a rather low yield (21%) [238], whilst Tsoureas et al. chose the reduction of the corresponding phosphane oxide with SiHClj under harsh conditions and had no control over the anion [282]. This prompted Wolf et al. to develop a third route [290], another modification of Nolan s protocol [238]. 

Carbene transfer to palladium yields the palladium complex [Pd(pincer)Me]Cl that undergoes a 1,2-methyl shift to form a pendant imidazolium salt at 150 °C in DMSO. This makes the pincer carbene ligand still relatively thermally stable with regard to reductive elimination. This is probably due to the difficulty encountered by the NHC unit in the pincer carbene ligand to orientate itself perpendicular to the pyridyl plane, the most favourable orientation for the reaction with the cix-methyl group. 

Alternatively, free NHCs have been obtained from imidazolium salts by electrochemical or chemical reduction. Coulometric analysis showed a single electron event, suggesting that the reduction proceeds via an imidazole radical, with further loss of one radical hydrogen to afford the free carbene (equation 4). 

Further investigations on reductive elimination processes showed that this reductive elimination could be the side reaction leading to degradation of active species in C-C cross-coupling reactions. As illustrated in Scheme 31, palladium-based catalyst (93) underwent oxidative addition in the presence of iodobenzene, providing the reaction intermediate (183), which could be involved in the catalytic cycle but also affords the imidazolium salt (184) by direct reductive elimination. Since then, a few other examples of... 

The aromaticity of the imidazole nucleus ensures stability towards reduction, and when benzimidazole (27) is hydrogenated over Adams catalyst in acetic acid the carbocyclic ring is reduced first to give the tetrahydrobenzimidazole (28). However, if the solvent is changed to acetic anhydride, A(-acylation promotes the reduction of the heterocycle and the 1,3-diacetylbenzimidazoline (29) is then formed (Scheme 1). Imidazole (30) under these conditions gives 1,3-diacetylimidazoline (31). Imidazolium salts (32) are easily reduced and treatment with excess sodium borohydride in 95% aqueous ethanol culminates in the formation of 1,2-diamines, (33) or (34). Either N—C bond may cleave, although if the substituent R is benzyl the major products are benzylamines (33 R = Bn). ... 

The reaction of several simple imidazolium salts (257) in 95% ethanol, employing a large excess of NBH, led to reductive ring cleavage to the diamines 258 and 259. The major product was 258 (77-93%) and the minor product, 259 (3-22%). Thus the predominant cleavage is between C-2 and A -benzyl. Similar reduction of l-methyl-3-(2-phenylethyl)imida-zolium iodide (260) gave 262 as the major product (92%). ... 

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