Azolium reaction with electrophile

Reaction of azolium salts with electrophiles via azolium carbanions... 

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... 

The general strategy for carrying out these MCRs starts with the generation of the NHC, which involves the deprotonation of the corresponding azolium salt by an appropriate base. Next, this carbene reacts with several electrophiles to produce reactive zwitterionic intermediates (typically from reaction with carbonyl compound or activated alkynes), followed by different rearrangements, rendering the final product. In this section, only examples based on thiazol-2-ylidenes... 

A series of azolium enolates (99 Ar = phenyl, mesityl) have been synthesized and characterized. Their ambident reactivities have been measured by studying their reactions with benzhydryl cations, Ar2CH , in r/ -acetonitrile, using known electrophilicity parameters for the latter. NMR shows predominantly 0-attack initially, with a switch to C-product over 1-2 days, with second-order rate constants for the two processes calculable. The azolium enolate reactivities have been compared with those of the corresponding free carbenes, and deoxy-Breslow intermediates. 

In order to separate structural effects from the electronic differences of these two catalyst classes. Bode synthesized chiral imidazolium salt 57 (Scheme 14.28). This allowed direct comparison of imidazolium versus triazolium precatalysts across a number of different reaction manifolds including those involving the catalytic generation of homoenolate equivalents, ester enolate equivalents, and acyl anions. These studies conclusively demonstrated that imidazolium-derived catalysts are superior for homoenolate reactions with less reactive electrophiles, while the triazolium-derived pre-catalysts are preferred for all other reactions. Interestingly, from the currently published body of the work, it does not appear to be any effects from the counterion of the azolium pre-catalysts in the presence of bases. 

There are three groups of substrates for which SNH reactions are especially characteristic (i) neutral azines and azoles (ii) azinium and azolium salts and (iii) nitro-arenes. Their electron-deficiency and, thus, their ability to react with nucleophiles strongly differ from each other. Azinium salts are the more electrophilic and are able to add even neutral nucleophiles very easily. Triazines,. v-tetrazines and polynitro-arenes also possess high electrophilicity. At the same time substrates such as pyridine (82JHC1285, 72JA682) and cinnoline (03CHE87), at a low temperature (e.g. in liquid ammonia as a solvent), do not react even with sodium amide. It should also be... 

As with pyridine, not only does the electronegative nitrogen atom withdraw electron density from the ring, but under the acidic conditions of many electrophilic reactions the azole nitrogen is protonated. The azolium cation is relatively inert to further attack by a positively charged electrophile. 

General Discussion. 2-(Trimethylsilyl)thiazole (1) reacts with various C-electrophiles such as azolium halides (eq 2), ketenes (eq 3), acyl chlorides (eq 4), 7 ketones, and aldehydes (eq 5) under mild conditions to give the corresponding 2-substituted thiazoles in very good isolated yields. No catalysts are required in these carbodesilylation reactions. 

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