Imidazole-based ylides

Imidazole-based Ylides (Table 8, entry 36) Polymer-bound acyl imidazolinium species display special reactivity. They can be deprotonated at their C-atom to form azolium yhdes, which can be trapped with benzaldehyde. Intramolecular transacylation involving the polymer-bound carboxyl group ensues to give the a-acyloxy methyl imidazole [487] (Scheme 136). 

Fischwick has detailed a rapid synthetic approach to the imidazole based y-lactam alkaloid, (+/—) cynometiine (67), isolated from the stem bark of Cynometra hankei, and which has been shown to be a potential analgesic (16). Cesium fluoride induced formation of the ylide, from precursor 68, followed by cycloaddition to alkene 69 furnished the required adduct 70 in 71% yield as a 4 1 diastereomeric mixture in favor of the desired isomer. Deprotection of the thioketal followed by NaBH4 reduction delivered the desired racemic product (Scheme 3.17). 

An acid- and base-sensitive siloxycarboxylic acid was treated with AW -carbonyldi-imidazole and the resulting imidazolide (51) transformed into the desired ylide using one equivalent of salt-free methylenetriphenylphosphorane in benzene, rather than two equivalents as usually recommended. Coupling, under neutral conditions, with two equivalents of aldehyde (52) gave a mixture of diastereomeric epoxythiolates (Scheme 15).68... 

In many examples of base-catalyzed exchange, the protonated azole is attacked by hydroxide ion to form an ylide in the rate-determining step, e.g., for imidazole (Scheme 62). Deuteration of imidazole is fast at the 2-position and much slower at the 4- and 5-positions. Rates fall off for N-unsubstituted imidazoles at high pH values because of the formation of unreactive anions. In the case of 1-methylbenzimidazole, the rate of hydrogen exchange in the 2-position is independent of the acidity over a wide range, in agreement with the mechanism shown in Scheme 62. 

The base-catalyzed deuteration at C-2 of imidazole quaternary salts proceeds via an ylide. Exchange at C-2 in 1,3-dimethylimidazolium is 3xl0 times as fast as 3- (or 5-) deuteration in 1,2-dimethylpyrazolium. 

The ring protons of nitro- and fluoroimidazoles (and their iV-methyl derivatives) also undergo base-catalyzed exchange in D2O by a combination of ylide and carbanion pathways. " In the 4-substituted imidazoles carb-anion exchange occurs more readily at C-5 than at C-2 e.g., for 1-methyl-... 

Base-induced cycloaddition of TosMlC 37 to N-sulfonylaldimines 36 affords 4(5)-monosubstituted imidazoles 38 from which the parent imidazoles 39 can be prepared <97T11355>. This type of chemistry has been extended to reaction with arylazosulfones <97T2125>. N-Sulfonyl-2-imidazolines are derived from the ruthenium complex catalyzed reaction between isocyanoacetate and analogs of 36 <97JOC1799>. Cycloaddition of ylide 40 with trifluoroacetonitrile gives trifluoromethyl substituted imidazolines <97TL4359>. 

Certain electron-deficient triazoles, such as l-sulfonyl-l,2,3-triazoles, could undergo ring-chain isomerism to generate diazo compounds. Based on this intrinsic ability of triazoles, Homeff et al. [44] developed Rh-catalyzed transannulation of l-sulfonyl-l,2,3-triazoles 66 with nitriles, which afforded imidazoles 67 in good to excellent yields (Scheme 5.46). In this process, l-sulfonyl-l,2,3-triazole serves as a precursor to diazoimine species A, which, in turn, could be converted to Rh-carbenoid B. Then a nucleophilic attack of nitrile at the Rh-carbenoid B leads to the ylide C, which undergoes cyclization and snbsequent metal loss to prodnce imidazole. 

---