Fast microwave-assisted preparation of aryl and vinyl nitriles and the corresponding tetrazoles from organo-halides

Aryl and vinyl nitriles have been prepared in very high yields from the cor responding bromides using palladium-catalyzed reactions with microwave irra diation employed as the energy source. Furthermore, flash heating was used successfully for the conversion of these nitriles into aryl and vinyl tetra zoles by cycloaddition reactions. One-pot transformation of aryl halides di rectly to the aryl tetrazoles could be accomplished both in solution and on solid support. All reactions were completed in minutes rather than in hour s or days as previously reported with the standard thermal heating techniqu e. A very potent HIV-1 protease inhibitor (K-i = 0.56 nM), comprising two t etrazole heterocycles as carboxyl group bioisosteres, was prepared in one p ot by microwave-promoted cyanation of a bromo precursor and a subsequent cy cloaddition reaction. The temperature-time profiles at 13, 20, and 60 W mag netron input power in DMF are presented.