Acidity azolium salts

In the case of azolium salts with acidic substituents the use of a sterically demanding base like KHMDS is required for a selective deprotonation at C2. 

A-Acylthioureas (149) treated with Bt2 or H2O2 in a perchloric acid medium give 1,2,4-dithi-azolium salts (150 X = C104 ) <8575371 >. Oxidation of (149) to the 1,2,4-dithiazolium salts was also carried out electrochemically, the A-acylurea having been isolated as a by-product <91JPR537>. When disulfides (151), obtained by Bt2 oxidation of (149 R = = H), are heated in AcOH 1,2,4-... 

All 1,4-(oxa/thia)-2-azolium salts are, in general, electrophilic species. Some of them, especially those where the positive charge is expected to locate predominantly inside the heterocyclic ring, are extremely electrophilic. Both kinds of oxathiazolium salts (6) and (7) exhibit this high electrophilic character, being attacked by solvents more nucleophilic than trifluoroacetic acid and nitromethane... 

As it has been shown, there are many ways to assemble the 1,4-(oxa/thia)-2-azole ring. Most of them are performed by inter- or intramolecular cyclization of suitable acyclic precursors. Some of them are found to be suitable for the synthesis of various ring systems, by using readily available, and properly modified reactants. Of particular importance are the following (a) the cyclizations of sulfenamides leading to (oxa/thia)azolium salts (Scheme 33) (b) the cyclization of hydroxamic acids (Scheme 39) (c) the dipolar cycloaddition methodology (Scheme 40) (d) the cyclizations of chlorosulfenyl chlorides (Scheme 46) and (e) the cyclizations of chloromethane sulfonamides (Schemes 47 and 48). Other cyclizations reported are preparative ways used mainly for the synthesis of specific compounds and the scope of these reactions has not been widely studied. 

The most common way to prepare N-heterocyclic carbenes is the deprotonation of the corresponding azolium salts, like imidazolium, triazolium, tetrazolium, pyrazolium, benzimidazolium, oxazolium or thiazolium salts or their partly saturated pendants, with the help of suitable bases. The pJCa value of imidazolium and benzimidazolium salts was determined to be between 21 and 24, which puts them right in between the neutral carbonyl carbon acids acetone and ethyl acetate [41,42], Arguably, imidazolium-based carbenes have proven to be especially versatile and useful and their synthesis should be discussed in more detail. The synthesis of imidazolium salts has been developed over many decades and numerous powerful methods exist [43]. 

The interesting electronic properties of NHC and their azolium precursors can be seen in the H- and C-NMR spectra for the and atoms. Since the W atom of an azolium salt is essentially acidic, the corresponding chemical shift will be observed downfield, typically at 5 = 8-11 ppm (see Figure 1.22). There is a correlation between the proton chemical shift and the ease of deprotonation [50]. The precursor of the acyclic carbene bis-(diisopropylamino)carbene, A, A, A ,A -tetraisopropylformamidinium chloride has a proton chemical shift of 5 = 7.60 ppm [118], significantly upheld of the normal range for azolium salts. 

A similar mechanism might operate in the activation of an azolium salt by a transition metal compound forming the metal carbene complex. However, since a basic substituent on the metal (acetate, alkoxide, hydride) usually reacts with the H -proton, the proton is removed from the reaction as the conjugate acid and reductive elimination does not occur. 

Steric protection can be provided by adamantyl wingtip groups that are introduced by the reaction of the l,r-diaminobiphenyl to the Schiff base (with 2-adamantone) followed by reduction with LiAlH [79,80] (see Figure 5.24). Ring closure with triethyl orthoformate to the corresponding azolium salt proceeds as usual and subsequent reaction with [Pd(allyl)Cl]j in the presence of a suitable auxiliary base (potassium tcrt-butylate) yields the respective palladium allyl complex. The paUadium(II) allyl complex can then be reacted with hydrochloric acid to form the [Pd(NHC)Cy dimer. Subsequent reaction with a silver(I) salt predictably breaks up the dimer under chloride abstraction and anion transfer from silver to palladium. 

Azolines 13C NMR, 5, 20 H NMR, 5, 17 NMR, 5, 14 Azolinethiones reactions, 5, 102-103 Azolinones acidity, 5, 72 13C NMR, 5, 16, 19 H NMR, 5, 14, 15 halogenation, 5, 58 hydrolysis, 5, 64 IR spectra, 5, 24, 27 reactions, 5, 81 with aldehydes, 5, 60 with ketones, 5, 60 Azolin-2-ones electrophilic attack, 5, 99 Azolium cations nucleophilic attack at carbon, 5, 61 reactivity, 5, 42 Azolium ions reactions with alkali, 5, 63 with amines, 5, 65 Azolium salts hydrogen exchange, 5, 70 nucleophilic attack at hydrogen, 5, 69-72 reactions... 

A range of azolium salts (143, X/Y = S/CH, NR/N, and NR/CH) have been prepared from f5j-pyroglutamic acid. They act as NHCs in the rhodium-promoted transfer... 

The efficiency of synthesized chiral azolium salts (260)-(262), derived from (5)-pyroglutamic acid, as carbene precursors was evaluated in the [Rh(cod)Cl]2-catalysed asymmetric transfer hydrogenation of aromatic ketones in isopropanol, acting as the hydrogen donor, and KOH as promoter to the corresponding alcohol. It was reported that the use of (262) displayed the highest activity and asymmetric induction for the transfer hydrogenation. The yield was up to 94% and enantioselectivities up to 90% ee were observed. ... 

Chiral azolium salts 52 and 53 have been used in the intramolecular vinylogous Stetter reaction of oxygen substrates 54 to provide 3-substituted chromanones (Scheme 77) (13CEJ15852). Other examples are obtained from the free-radical cascade reaction of O-allyl acylphosphonate with various functionalized P-ketoxanthates in the presence of dilauroyl peroxide, with moderate to good yields (130L4818). A series of 2,3-disubstituted chromanones are synthesized from the reaction of acrylic acids with arynes in the presence of CsF (13T2789). 

The chemistry of various nitrogen-rich energetic bicycUc azoliiun salts has been described. The thermally stable bicyclic azolium salts (78a-d, 81a-b, 84a-d, 85a,b, 86a,b) with densities ranging between 1.52-1.67 g/cm, were prepared by quaternization with nitric acid or perchloric acid or... 

Azolium salts, for example, imidazolium, triazolium, tetrazolium, pyrazolium, benzimidazolium, oxazolium, and thiazolium, are mostly used as precursors for the synthesis of NHCs (Scheme 2.152). The acidic hydrogen at C2 can be removed by the effect of a base. In a typical approach disclosed by the Arduengo group, the... 

The azolium salts acidity is determined not only by the type of heterocycle but also by the nature of the ring substituents (Figure 18.2) [9]. Despite the importance of the salts acidities, the pfCa of some of the most commonly used azolium salts has not been reported. Inferences can nevertheless be made in some cases. For instance, N-C Fs triazolium 17 was found to be completely deprotonated by one equivalent of l,8-diazabicycloundec-7-ene (DBU) in CD2CI2 whereas N-mesityl triazolium 18 was only partially deprotonated [10]. Of note, the use of very weak bases can be sufficient or even beneficial in some cases, despite the presence of only small amounts of active carbene catalyst in the reaction mixture [10, 11]. 

N-heterocyclic carbene catalysis has become one of the major categories in orga-nocatalysis. Azolium salts are ready deprotonated by weak bases to generate a carbene, which then adds to an aldehyde to form an acyl anion equivalent, generally called the Breslow intermediate. The reactive acyl anion attacks an electrophile to promote the various transformations such as benzoin, Stetter, and redox reactions [107]. Recently, an interesting approach for NHC-catalyzed generation of an enol/enolate intermediate was reported. Enantio-enriched (i-amino acid derivatives (217) are formed by the reaction between the a-aryloxyaldehyde 214 and N-tosyl-imines (215) in the presence of phenyalanine-derived azoUum salt 216 as a pre-catalyst and aryl phenoxide as a base (Scheme 28.28) [108]. 

Azolium salts are easily accessible, and different types of imidazolium, imid-azolinium and benzimidazolium salt can be deprotonated at the C2 position to yield the free NHCs. The first successful deprotonation of an imidazolium salt to the free NHC was achieved with NaH in THF/DMSO (see Scheme 1.4). Subsequently, other bases such as KOt-Bu or KH in THF or NaH in liquid ammonia " were used (Scheme 1.9). For azolium salts with acidic substituents or in the case of the formamidinium salts derived from six- or... 

Despite the considerable synthetic potential of this reaction, only two NHC-containing catalysts have been reported to date. The in situ generated complex from the reaction between [RhCl(COD)]2 and the NHC-silver ligand transfer reagent 20 was found to be active in the arylation of an At-phosphi-noyl aldimine with phenylboronic acid but unfortunately only one catalytic test was performed [eqn (8.9)]. In a more systematic study, Suzuki and Sato screened various azolium salts, among which the system [RhCl(COD)]2/ lAd-HCl proved to be the most active catalyst for the arylation of a series of A -sulfonyl and A -phosphinoyl arylimines. ... 

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