Triazolium salts, preparation

Disubstituted triazolium salts are prepared from alkyl or aryl hydrazines via an oxadiazolium salt 28 (Scheme 16). Addition of a chiral amine on this salt resulted in a ring opening - ring closure reaction affording the triazolium salts 29. 

An enantiopure bicyclic triazolium salt was prepared by a three step conversion of the oxazolidinone 31 (Scheme 18). The first step was a methylation affording an iminoether which was transformed into the phenylhydrazone 32. A final cyclization gave the salt 33 as a cristalline solid [25]. 

This homoenolate methodology has been extended to the use of nitrones 170 as electrophiles [72]. Scheldt and co-workers have shown that enantiomerically enriched y-amino esters 172 can be prepared with excellent levels of stereocontrol from an enal 27 and a nitrone 170 using the NHC derived from triazolium salt 164 (Scheme 12.37). The oxazinone product 171, formally a result of a [3-1-3] cycloaddition, is cleaved to afford the y-amino ester product 172. The reaction shows broad substrate scope, as a range of substituted aryl nitrones containing electron donating and withdrawing substituents are tolerated, while the enal component is tolerant of both alkyl and aryl substituents. 

The synthesis of pyrazolo[4,3-rf]-l,2,3-triazine starting from a pyrazolo-3-carbaldehyde derivative has been reported <00JIC168>. Azolo-l,2,4-triazine derivatives have been prepared via the reaction of functionalized thiazole derivatives with several heterocyclic diazonium salts <00JCR(S)206>. The reaction of 1,2,4-triazolium salt 67 with alkene 68 gives the pyrrolo[2,l-/][l,2,4]triazine 69 <00H(53)213>. 

In order to vary the electronic situation at the carbene carbon atom a number of carbo- and heterocycle-annulated imidazolin-2-ylidenes like the benzobis(imida-zolin-2-ylidenes) [58-60] and the singly or doubly pyrido-annulated A -heterocyclic carbenes [61-63] have been prepared and studied. Additional carbenes derived from a five-membered heterocycle like triazolin-5-ylidenes 10 [36], which reveals properties similar to the imidazolin-2-ylidenes 5 and thiazolin-2-ylidene 11 [37] exhibiting characteristic properties comparable to the saturated imidazolidin-2ylidenes 7 have also been prepared. Bertrand reported the 1,2,4-triazolium dication 12 [64]. Although all attempts to isolate the free dicarbene species from this dication have failed so far, silver complexes [65] as well as homo- and heterobimetallic iridium and rhodium complexes of the triazolin-3,5-diylidene have been prepared [66]. The 1,2,4-triazolium salts and the thiazolium salts have been used successfully as precatalysts for inter- [67] and intramolecular benzoin condensations [68]. 

Triazolium salts can be prepared from thiazolium salts by treatment with amines (Equation (69)) <74ZOR377>. Methylthiothiazolium salts react similarly (Scheme 36) <73IJC753>. 

Scheme 31. Preparation of triazolium salts 123 derived from pyroglutamic acid...

Triazolium salts (49 Scheme 23), prepared from an acid chloride and the thiohydrazo compound (48), have been reduced to the hydro compound (50) and then hydrolyzed in dilute sulfuric acid to the aldehyde. - Overall yields of aldehyde are reported to be 46-90% and a variety of other functional groups can be supported such as alkene, halogen, nitro, ketone and ester there can be one or two side chains on the a-carbon or it can be part of an alicyclic system. 

Fig. 14 [3 + 2]Cycloaddition-quaternisation sequence for preparation of triazolium salts...

Of the ring systems under discussion in this chapter, only the pyrrolotriazoles (2) and (3) and the pyrrolothiadiazoles (7) have been prepared by more than one route. For example, pyrrolo[l,2-6][l,2,4]triazoles (2) have been prepared (i) by cyclization of substituted triazolium salts (Equation (1)), a [5 + 0] synthesis (ii) from cyclic amidrazone (73, Scheme 11), a [4 + 1] synthesis (iii) from thiosemicarbazides (90, Scheme 15), a synthesis involving simultaneous formation of both rings and (iv) from triazolo[4,3-6]pyridazines (94, Scheme 16) by photochemical addition of an alkene. However, as each of these routes yields different groups of products and no individual compound has been prepared by more than one of these routes, it is not possible to compare them in a meaningful manner. The same is true for ring systems (3) and (7). 

Using similar chemistry, the construction of perfiuoroalkyl-substituted 1,2,4-triazoles can be readily accessed through a three-component condensation reaction of aperfiuoroalkyl ester, a hydrazine, and an amidine. For example, Shreeve and coworkers prepared a series of alkylated 3-perfiuoroalkyl, 5-dimethyl-l,2,4-triazolium salts... 

In the same year, a series of Ci-symmetric chiral triazolium Pd(II) complexes were prepared by Enders et al. As typically reported with the use of Ci-symmet-ric ligands, their NHC-metal complexes were obtained as diastereomeric mixtures due to the restricted rotation around the carbene-metal bond [6]. Without further elaboration, the authors stated that these complexes were used in an enantioselective Heck-type reaction achieving low asymmetric inductions. Soon thereafter, the authors investigated the coordination behavior of chiral triazolium salts 35 with [Rh(COD)Cl]2 and obtained a mixture of axially chiral complexes 36 with a diastereomeric excess of up to 94% (Scheme 3.20). These complexes were used as catalysts in asymmetric hydrosilylation reactions, achieving up to 44% ee for aromatic and ahphatic ketones [38,39]. 

The 1,2,4-triazolium salt 102 (Figure 1.10) was prepared by Bertrand and co-workers. Even if all attempts to isolate the free dicarbene by deprotonation of the dication failed thus far, it was possible to obtain the mono- and disilver complexes by deprotonation and metalation of the carbon atoms of the hete-rocycle. Peris and co-workers obtained the diiridium complex by reaction of 102 (R = Me) with two equivalents of IrCl(COD)]2 in the presence of KOt-Bu. A heterobimetallic Ir Rh complex was obtained by successive reaction of 102 with [IrCl(COD)]2 and [RhCl(COD)]2. ... 

A flame dried round-bottom flask was charged with triazolium salt 46 (0.2 equiv) and toluene (5 mL). To this solution was added KHMDS (0.5 M in toluene prepared prior to use from 0.05 g of KHMDS in 0.5 mL of toluene) (0.2 equiv) via syringe, and the solution was stirred at ambient temperature for 5 min. A solution of 43 (1 equiv, 0.12 mmol) in toluene (2 mL) was added. The resulting solution was allowed to stir at ambient temperature and monitored by TLC. The reaction mixture was placed directly onto a silica gel column. The desired product was purified by flash column chromatography, eluted with a suitable solution of hexane and ethyl acetate (typically 4 1). Evaporation of solvent afforded analytically pure product 44. 

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