Pyridinium-ylides

Pyridinium ylide, 1-ethoxycarbonylimino-photolysis, 2, 313 Pyridinium ylide, N-imino-photolysis, 2, 314 synthesis, 2, 185 Pyridinium ylides, 2, 336 photolysis, 2, 313-314 Pyridin-2-one, 3-acetyl-synthesis... 

Pyridinium ylide is considered to be the adduct car-bene to the lone pair of nitrogen in pyridine. The validity of this assumption was confirmed by Tozume et al. [12J. They obtained pyridinium bis-(methoxycarbonyl) meth-ylide by the photolysis of dimethyl diazomalonate in pyridine. Matsuyama et al. [13] reported that the pyridinium ylide was produced quantitatively by the transylidalion of sulfonium ylide with pyridine in the presence of some sulfides. However, in their method it was not easy to separate the end products. Kondo and his coworkers [14] noticed that this disadvantage was overcome by the use of carbon disulfide as a catalyst. Therefore, they used this reaction to prepare poly[4-vinylpyridinium bis-(methoxycarbonyl) methylide (Scheme 12) by stirring a solution of poly(4-vinylpyridine), methylphenylsulfo-nium bis-(methoxycarbonyl)methylide, and carbon disulfide in chloroform for 2 days at room temperature. 

On the other hand, poly(ethoxycarbonylimino-4-vi-nylpyridinium ylide) (Scheme 13) was prepared essentially by the same method from 1-ethoxycarbonylimino-pyridinium ylide, as described by Hafner [15] from the reaction of poly (4-vinylpyridine) with nitrene, generated from the pyrolysis of ethyl azidoformate. 

The initial step in Scheme 91 presumably involves deprotonation of the phenacyl substituent to give a pyridinium ylide. Such ylides may be generated as reactive (unstable) intermediates in the synthesis of cycl[3.2.2]azines from iV-(trimethylsilylmethyl)-2-pyridones (Scheme 92) in the presence of an excess of DMAD, the cyclazine is the major product <2003S1398>. 

The reaction of 196 with phenyl chlorocarbene 198 illustrates the synthesis of indolizines by cyclization of pyridinium ylides (Scheme 7). Cyclization of ylide rotamer 199 generates the intermediate product 200, which undergoes elimination of chloride to provide compound 201 <2005EJ01532>. 

Imidazolium, thiazolium and pyridinium ylides 198 also react with the acylmethylenecyclopropenes 208-210 to give the analogous heterocyclic cage compounds 212 (Table 20). 

Another example with porphyrinic dipolar species uses pyridinium salt derivatives as precursors of porphyrinic pyridinium ylides (Scheme 18) <05TL5487>. The procedure involves the reaction of porphyrin 58 with methyl bromoacetate, in refluxing chloroform, to give pyridinium salt 59. The latter, in the presence of K2CO3, reacts with 1,4-benzoquinone to yield only the mono-addition compound 60. Notably, when the reaction was performed in the presence of DBU, bis-addition occurred and the porphyrinic dimer 61 was the only isolated addition product. 

Scheme 18. 1,3-DC reactions of porphyrinic pyridinium ylide with 1,4-benzoquinone.

Another classic reaction of pyridinium salts is reduction of the pyridine ring. Donohoe and co-workers reported the partial reduction of A-alkylpyridinium salts <060BC1071>, which is accompanied by subsequent alkylation and hydrolysis to furnish a range of 2,3-dihydropyrid-4-ones. This sequence has the potential to introduce a variety of functional groups at the C-2 position of 2,3-dihydropyrid-4-ones. Reduction of pyridinium ylides with sodium borohydride has also been reported in fair to good yields <06JHC709>. 

An interesting iridium-catalysed 5-CH boronation of 2,3-dimethylpyrazine was reported incidentally in a paper mainly devoted to the reaction of pyridines. The product 89 was used in a Suzuki coupling <06AG(I)489>. Selective mono coupling of 2,6-dichloropyrazine with boronic acids, followed by amine displacement of the second chlorine has been used to prepare potential anti-cancer compounds <06JMC407>. A full paper has been published on the chelation-driven selective Suzuki coupling of the pyridinium ylides 90 <06TL6457>. 

Diazepines are formed in almost quantitative yield in the irradiation of pyridinium ylides (3.35) 3540. 

When, however, carbenes are directly generated from diazoalkanes, RIES becomes significant.56 Photolytic generation of carbene 45 from diazoalkane precursors in the presence of >1.5 M pyridine gave values for the derived pyridinium ylides. 

The yields of carbene (and pyridinium ylide) are thus controlled by competition between simple nitrogen loss to the carbene or 1,2-H (or 1,2-C) shift linked to nitrogen loss in the excited state of the diazoalkane precursor 56 When R=i-C3H7, the a-CH bond is weak, there is much RIES upon diazoalkane photolysis, and carbene production is inefficient. When R=/-C4H9 (no a-CH bond) or R=cyclo-CjU5 (strong a-CH bond), diazoalkane photolysis gives little RIES and much carbene.56... 

A useful method for the synthesis of 1-unsubstituted 2-arylindolizines is provided by the 1,5-dipolar cyclization of pyridinium ylides derived from 181, in the presence of the oxidant tetrakis(pyridine)cobalt(ll) dichromate (TPCD), which oxidizes the intermediate dihydroindolizine 182 (Scheme 43). The study demonstrated that the presence of an aryl group on the double bond was necessary for the reaction to occur. 

Yields from 1,3-dipolar addition reactions with pyridinium ylides are enhanced by the addition of phase-transfer catalysts [60]. The ylides are produced in situ under basic two-phase conditions and react at room temperature with acetylenic dipolarophiles. 

Several reaction sequences have been reported in which Fischer-type carbene complexes are converted in situ into non-heteroatom-substituted carbene complexes, which then cyclopropanate simple olefins [306,307] (Figure 2.22). This can, for instance, be achieved by treating the carbene complexes with dihydropyridines, forming (isolable) pyridinium ylides. These decompose thermally to yield pyridine and highly electrophilic, non-heteroatom-substituted carbene complexes (Figure 2.22) [46]. 

In a one-pot reaction (Scheme 126) the iminophosphorane of 6-aminoura-cil (346) (92AHC129) is transformed with isocyanate in the presence of pyridine into a nonisolable carbodiimide. Spontaneous addition of pyridine follows to give a 1,6-dipolar pyridinium ylide (347), which cyclizes to the... 

The perfluoroacetamide catalysts, rhodium(II) trifluoroacetamidate [Rh2(tfm)4] and rhodium(II) perfluorobutyramidate [Rh2(pfbm)4], are interesting hybrid molecules that combine the features of the amidate and perfluorinated ligands. In early studies, these catalysts were shown to prefer insertion over cycloaddition [30]. They also demonstrated a preference for oxindole formation via aromatic C-H insertion [31], even over other potential reactions [86]. In still another example, rhodium(II) perfluorobutyramidate showed a preference for aromatic C-H insertion over pyridinium ylide formation, in the synthesis of an indole nucleus [32]. Despite this demonstrated propensity for aromatic insertion, the perfluorobutyramidate was shown to be an efficient catalyst for the generation of isomtinchnones [33]. The chemoselectivity of this catalyst was further demonstrated in the cycloaddition with ethyl vinyl ethers [87] and its application to diversity-oriented synthesis [88]. However, it was demonstrated that while diazo imides do form isomtinchnones under these conditions, the selectivity was completely reversed from that observed with rhodium(II) acetate [89, 90]. 

Aldehydes will condense with pyridinium ylides in a manner similar to the Knoevenagel condensation (Scheme 66) (53AG617). However, the corresponding condensation of aromatic nitroso compounds results in the elimination of the parent heterocycle, the product being a nitrone. The reaction is illustrated with phenacylisoquinolinium bromide (71 Scheme 66). 

Pyridinium ylides will undergo dipolar cycloaddition reactions the topic has been reviewed (B-76M120601). 

Reaction with pyridine leads to the formation of a UV-active pyridinium ylide. Rate constants for the alkylcarbene reaction(s) can be extracted from the intercept of the linear correlation of feobs for ylide formation versus the pyridine concentration. Consider first the 1,2-H shift that converts chloromethylcarbene (48) into vinyl chloride (Scheme 7.17). The LFP experiments show that the H shift occurs with k= 1.2 — 3.0 X 10 s in isooctane, cyclohexane, or dichloroethane at 21-25 The rearrangement is fast, but not ultrafast carbene (48) has a lifetime... 

CHMe, cyclopropylidene, and CMe2 to activated double bonds.1075 Similar reactions have been performed with phosphorus ylides, 076 with pyridinium ylides,1077 and with the compounds (PhS)3CLi and Me3Si(PhS)2CLi.1078 The reactions with ylides are of course nucleophilic addition. 

There are two routes to [l,2,4]triazolo[l,5-a]pyridines from N-aminopyridinium salts. In one, Ar-(2-pyridyl)hydrazides (34) are converted by MSH (mesitylsulfonylhydroxylamine) to AZ-aminopyridinium salts, and these cyclize on heating, giving 1-aminotriazolopyridinium salts C35).4 In the other, AZ-aminopyridinium salts are treated with AZ-ethoxycarbonylacet-imidate to give pyridinium ylides (36), which cyclize on heating, giving mixtures of triazolopyridines and imidazopyridines.47,48... 

Cyanides can react with 1-aminopyridinium salts to give 2-substituted triazolopyridines, possibly via the pyridinium ylide. With 1-aminopyridinium iodide and cyanide ion the intermediate 4-cyanopyridine reacts with the aminopyridinium salt to give 2-(4-pyridyl)triazolopyridine (45).51 When acetonitrile or benzonitrile are used, 2-methyl- and 2-phenyltriazolo-pyridines are obtained.58 60 The reaction is thought to involve a dipolar cycloaddition of the N- mi nopyridine with the nitrile, as shown in Eq. (4). 

The reaction of triplet diphenylcarbene with pyridine has been well studied, and a mechanism proposed from kinetic data (90TL953). The carbenes generated from laser flash photolysis of alkylbromo- and alkylfluoro-diazirines were trapped by pyridine to form the pyridinium ylides... 

Following the canonical structure (166a) the pyridinium ylide may be expected to act as a 1,3-dipole, the reactivity of which depends on the substituents X and Y. Combinations of hydrogen, alkyl and aryl together with acyl, alkoxycarbonyl, sulfonyl and cyano groups appear to be suited for a cycloaddition. 

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