Imidazolium salts, preparation

A variety of silver(I) carbenes can be prepared by interaction of a series of imidazolium salts with silver(I) oxide or silver(I) carbonate (OOJCS(D) 4499). With 3-tert-butyl-l-(2 -pyridylmethyl)imidazolium bromide hydrate and 3-(2", 6"-di-Ao-propylphenyl)-l-(2 -pyridylmethyl)imidazolium bromide hydrate, complexes 85 (R = t-Bu, 2",6"-/-Pr2CgH3) result. 3-(2",4",6"-Trimethylphenyl)-l-(2 -pyridylmethyl)imidazolium bromide in turn leads to 86 (R= 2",4",6"-MejCgH2). 3-(2",6"-Di-wo-propylphenyl)-l-(2 -pyridyl)... 

Symmetrical N, N -disubstituted imidazolium salts are usually obtained by addition of paraformaldehyde on a bis-imine of glyoxal under acidic conditions. A one-pot procedure has been developed. Several enantiomerically pure amines were used to prepare the corresponding symmetrical salts 6 (Scheme 4) [12,13]. 

Gade and Bellemin-Laponnaz have reported the synthesis, in good yields, of chiral oxazoline-imidazoliums salts 10a (Scheme 8) obtained by reaction of 2-bromo-4(S)-t-butyl oxazoline with several mono-N-substituted imidazoles [16]. Similaly an imidazolium salt 10b bearing a paracyclophane substituent was prepared by Bolm [17]. 

RajanBabu reported the first preparation of a bis-imidazolium salt 15 bearing a chiral linker (Scheme 11). The starting material was the enantiomerically pure (S)-l,l -bi-2-naphtol bis(trifluoromethanesulfonate) which was transformed in two steps into the dibromomethyl derivative 16 and then into the bis-imidazole. Quaternarization of this compound afforded 15 [20]. 

A bis-imidazolium salt was also prepared by Burgess, starting from the dichloride 20 derived from optically pure N,N -dimethyl-tmns-l,2-diaminocyclohexane (Scheme 13). The salt 21 was obtained by addition of this compound to several 1-alkylimidazoles [22]. 

The ruthenium complexes were prepared in 50-80% yield by treatment of the imidazolium salts with potassium hexafluoro-t-butoxide, and then by (PCy3)2Cl2Ru = CHPh. A single phosphine is displaced by the carbene affording the desired complexes as air-stable solids that were purified by silica gel... 

We initially tested Candida antarctica lipase using imidazolium salt as solvent because CAL was found to be the best enzyme to resolve our model substrate 5-phenyl-l-penten-3-ol (la) the acylation rate was strongly dependent on the anionic part of the solvents. The best results were recorded when [bmim][BF4] was employed as the solvent, and the reaction rate was nearly equal to that of the reference reaction in diisopropyl ether. The second choice of solvent was [bmim][PFg]. On the contrary, a significant drop in the reaction rate was obtained when the reaction was carried out in TFA salt or OTf salt. From these results, we concluded that BF4 salt and PFg salt were suitable solvents for the present lipase-catalyzed reaction. Acylation of la was accomplished by these four enzymes Candida antarctica lipase, lipase QL from Alcaligenes, Lipase PS from Burkholderia cepacia and Candida rugosa lipase. In contrast, no reaction took place when PPL or PLE was used as catalyst in this solvent system. These results were established in March 2000 but we encountered a serious problem in that the results were significantly dependent on the lot of the ILs that we prepared ourselves. The problem was very serious because sometimes the reaction did not proceed at all. So we attempted to purify the ILs and established a very successful procedure (Fig. 3) the salt was first washed with a mixed solvent of hexane and ethyl acetate (2 1 or 4 1), treated with activated charcoal and passed into activated alumina neutral type I as an acetone solution. It was evaporated and dried under reduced... 

In the reaction of the very reactive phosphoric triimidazolide (for preparation see Section 2.2), which is also called phosphoryltriimidazole in analogy to the carbonyldii-midazole CDI, with an excess of methanol, as products trimethyiphosphate, dimethyl-phosphate, and O-methylphosphoric imidazolide were detected after one hour, and after two days the imidazolium salt of dimethylphos-phate was obtained in high yield [13]... 

Pentacoordinate silicon complexes can also be prepared via the reaction of diaryldichlorosilanes with carbenes 4 (R = Et, Pr R = Me). Interestingly, a 2-(trimethylsilyl)imidazolium salt (56) was formed when Me3SiI was treated with 4 (39). Unfortunately, no information regarding the crystal structures of these species is available. 

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]. 

Imidazolium salts that can be prepared by the first procedure, the alkylation of imidazole, are easy to obtain and often used for metal complex synthesis. Potassium imidazolide is reacted with the first equivalent of alkyl halide in toluene to give the 1-alkylimidazole. Subsequent alkylation in 3-position is achieved by addition of another equivalent of alkyl halide [Eq. (2)]. " A variant of this approach employs commercially available A-trimethylsilyl imidazole with 2 equiv of an alkyl chloride, under elimination of volatile MesSiCl. The drawback of these simple routes is the fact that only primary alkyl halides can be reacted in satisfactory yields because secondary and tertiary alkyl halides give substantial amounts of elimination by-products. 

In order to introduce other substituents at the 1- and 3-positions of the imidazolium salt the reaction of primary amines with glyoxal and formaldehyde in the presence of acid can be used [Eq. (3)]. ° Variation of the amine allows the preparation of imidazolium salt libraries which can be diversified by using... 

In cases where the free NHC cannot be synthesized the complex formation has to be accomplished in situ from a ligand precursor, e.g., the imidazolium salt in the case of imidazolin-2-ylidenes. By this method, it is often possible to prepare complexes which do not have the maximum number of NHC ligands attached to the metal center. 

The most common methods suitable for the synthesis of different azolium compounds will be discussed here. Two routes are particularly useful for the preparation of the imidazolium salts (1) substitution reactions at the nitrogen atoms of imidazole [25] and (2) multicomponent reactions for the generation of an Af,Af -substituted heterocycle which are particularly useful for the synthesis of imidazolium salts bearing aromatic, very bulky, or particularly reactive N,N -sub-stituents (Fig. 3a,b) [26]. Both methods offer the opportunity to produce unsym-metrically substituted imidazolium salts of type 1 either by stepwise alkylation of imidazole or by the synthesis of an W-arylated imidazole derivative followed by 77 -alkylation [27]. Nevertheless, the method of choice for the preparation of the imidazolium salts 1 is the 77,77 -substitution of imidazole. Several other methods for the preparation of imidazolium salts with previously unattainable substitution patterns have also been described [28, 29]. 

Although these two methods have found widespread application for the synthesis of free carbenes, they failed for selected saturated imidazolidin-2-ylidenes and especially in the preparation of triazolin-5-ylidenes. In these cases the free carbene species 7 can be obtained from 2-alkoxyimidazolidines 6 [44] or 5-aUcoxytriazoles [36] by thermally induced ot-elimination of an alcohol (Fig. 5). In addition to 2-aUcoxyimidazolidmes, 2-(pentafluorophenyl)imidazolidines [45, 46] have also been used for the generation of NHCs by cx-elimination. The adduct 8 eliminates acetonitrile upon heating [47] to yield the benzimidazolin-2-ylidene 9. In a more exotic procedure, imidazolium salts have been reduced electrochemically to give the free imidazolin-2-ylidenes [48]. 

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]. 

Also the use of moisture stable ionic liquids as solvents in the Diels-Alder reaction has been carried out, and in all examples an enhanced reaction rate was observed [182,183]. The application of pyridinium-based ionic liquids allowed the utilization of isoprene as diene [184]. The chiral ionic liquid [bmim][L-lactate] was used as a solvent and accelerated the reaction of cyclopentadiene and ethyl acrylate, however, no enantiomeric excess was observed [183]. In addition several amino acid based ionic liquids have been recently tested in the Diels-Alder reaction. Similar exo. endo ratios were found but the product was obtained as racemate. The ionic liquids were prepared by the addition of equimolar amounts of HNO3 to the amino acids [185]. Furthermore, an enantiopure imidazolium salt incorporating a camphor motive was tested in the Diels-Alder reaction. No enantiomeric excess was found [186]. 

The ionic liquid [bmim][BF ] is known to catalyze the aza-Diels-Alder reaction in the synthesis of pyrano- and furanoquinolines [190]. This reaction was also catalyzed by the enantiopure bis-imidazolinium salt 67 in 67% yield with an endo. exo ratio of 60 40 (Scheme 69) [191]. The product was obtained as a race-mate. In addition the aza-Diels-Alder reaction with imines and Danishefsky s diene was catalyzed by the salt 67 giving racemic product. The salt and its analogues could be easily prepared via the oxidation of the corresponding aminals [192]. Investigation of the influence of the counter anion in achiral C2-substituted imidazolinium salts, which can be also described as 4,5-dihydroimidazolium or saturated imidazolium salts, in the aza-Diels-Alder reaction showed, that the catalytic activity increased, the more lipophilic the counter anion and therefore the more hydrophobic the salt was [193]. 

An ionic liquid was fully immobilized, rather than merely supported, on the surface of silica through a multiple-step synthesis as shown in Fig. 15 (97). A ligand tri(m-sulfonyl)triphenyl phosphine tris(l-butyl-3-methyl-imidazolium) salt (tppti) was prepared so that the catalyst, formed from dicarbonylacetylacetonate rhodium and the ligand (P/Rh = 10), could be soluble in both [BMIMJBFq and [BMIM]PF6. The supported ionic liquid-catalyst systems showed nearly three times higher rate of reaction (rate constant = 65 min ) that a biphasic system for the hydroformylation of 1-hexene at 100°C and 1500 psi in a batch reactor, but the n/i selectivity was nearly constant the same for the two ( 2.4). Unfortunately, both the supported and the biphasic ionic liquid systems exhibited similar metal leaching behavior. 

The oxidation of alkenes to diols via l,2-bis(boronate) esters was reported for a silver(l) NHC complex 17 [ 109]. 1-Methyl-3-(+)-methyhnenthoxide imi-dazoUum chloride was used as the precursor together with an excess of Ag20 (Scheme 21). The resulting complex was significantly more active than when prepared in situ from Ag20 and the imidazolium salt. 

Imidazolium ligands, in Rh complexes, 7, 126 Imidazolium salts iridium binding, 7, 349 in silver(I) carbene synthesis, 2, 206 Imidazol-2-ylidene carbenes, with tungsten carbonyls, 5, 678 (Imidazol-2-ylidene)gold(I) complexes, preparation, 2, 289 Imidazopyridine, in trinuclear Ru and Os clusters, 6, 727 Imidazo[l,2-a]-pyridines, iodo-substituted, in Grignard reagent preparation, 9, 37—38 Imido alkyl complexes, with tantalum, 5, 118—120 Imido-amido half-sandwich compounds, with tantalum, 5,183 /13-Imido clusters, with trinuclear Ru clusters, 6, 733 Imido complexes with bis-Gp Ti, 4, 579 with monoalkyl Ti(IV), 4, 336 with mono-Gp Ti(IV), 4, 419 with Ru half-sandwiches, 6, 519—520 with tantalum, 5, 110 with titanium(IV) dialkyls, 4, 352 with titanocenes, 4, 566 with tungsten... 

A new type of triaryl phosphine-functionalized imidazolium salt containing cations such as (6) has been prepared. Palladium complexes of (6) generated in situ have been used successfully in Heck-type reactions of aryl halides with acrylates and of 4-bromotoluene with styrene derivatives.34 The first Heck-type reaction of aryl halides with allenes has been reported. 1,3-Double arylations were observed with 3-substituted-l,2-allenyl sulfones, while 1-monoarylation was favoured with 3,3-disubstituted-l,2-allenyl sulfones.35 It has been shown that the a-arylation of methane-sulfonamides (7) may be achieved using palladium catalysis reaction proceeds through the sulfonamide enolates.36 It is also reported that palladium cross-coupling of alkynes with /V - (3 - i odophe n y I an i I i ncs) may lead to the formation of substituted carbazoles.37... 

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