Imidazoles reaction with benzynes

The molar ratio between benzyne and imidazole proved to have a critical influence on the direction of the reaction the benzyne/imidazole ratio was 1 3 in Yoshida s process, whereas a 1 1 ratio was employed by Xie and Zhang. The difference in substrate ratio apparently led to two entirely different reaction pathways. In Zhang s case, benzyne first underwent a Diels-Alder reaction with imidazole to produce the nitrogen-bridged isoquinoline intermediate 139. A subsequent retro Diels-Alder reaction led to intermediate 140 after the loss of hydrogen cyanide. This was followed by a second Diels-Alder reaction with benzyne to generate intermediate 141. Intermolecular nucleophilic addition of 138 to a third benzyne then gave rise to the final product arylamine 142. 

Fluoride-ion-mediated generation ofbenzyne from silylaryl triflates (41) [20] is mild and excellent in chemical yields andsoithasbeen employed for a variety of electrophilic (42) [21 ], nucleophilic (43) [22], and cycloaddition reactions [23] (Scheme 3.26). N-Phenylations of sulfonamides (44), amines (45) [24], azirines [25], oxazoles [26], pyrroles [27], and imidazoles [28] with benzyne from 41 are also known. 

Two sets of conditions have been developed for electron-rich heterocycle arylation [94, 95], Most acidic heterocycles such as benzoxazole or benzothiazole may be arylated by employing fBuOLi base, aryl iodide, and DMF solvent (Scheme 23). These reactions proceed at 140 °C in minutes. For less acidic imidazole, 1,2,4-triazole, and caffeine derivatives a stronger fBuOK base is required, and the reaction proceeds by a benzyne-type mechanism. Formation of regioisomer mixtures was observed if substituted aryl halides were used in combination with fBuOK (Scheme 23). 

A (1/7-imidazol-l-yl) silver species (55) has been postulated as the key intermediate in the 3-l-2-cycloaddition reaction of diazoalkanes (54) with benzynes yielding 2-aryl-2H-indazoles (56) (Scheme 18). The 3-I-2-cycloaddition reaction of 3-trifluoromethyl-4-diazopyrazolinones with dialkyl acetylene dicarboxylates, in refluxing toluene, produced spiro 3/f-pyrazole adducts that rearranged to the trifluoromethyl-substituted pyrazolo[l,5-fi(][l,2,4]triazin-7-ones. ° The 1,3-dipolar cycloaddition reaction of aromatic thioketones (58) with 2-aza-1,3-dicarbonyl compounds (57), at 20-50 C, yielded thiadiazoline adducts (59) that readily eliminate nitrogen to produce oxathioles (60) in moderate yields (up to 70%) (Scheme 19). ... 

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