Tandem Transformations of Nitriles into N-Heterocyclic Compounds by Electrophilic Trapping of Blaise Reaction Intermediates

Abstract

Tandem transformations of nitriles into various N-heterocycles have been accomplished through the reaction of electrophiles with Blaise reaction intermediates formed in situ. The reaction of the Blaise reaction intermediates with propiolates gives 2-pyridones through consecutive C- and N-nucleophilic reactions. The tandem reactions of the Blaise reaction intermediate with 1,3-enynes proceed through C-nucleophilic addition followed by an electrocyclization–aromatization cascade to give pyridines. Exocyclic enamino esters can be prepared by transformations of ω-chloroalkyl nitriles through chemoselective intramolecular alkylation of the Blaise reaction intermediate. Palladium-catalyzed intramolecular arylations or copper-catalyzed intermolecular cross-coupling reactions of the Blaise reaction intermediate give a range of indole derivatives. Combinations of tandem alkylations and palladium-catalyzed couplings of the Blaise reaction intermediates of ω-chloroalkyl nitriles give N-fused indoles.

Key words

nitriles - tandem reactions - heterocycles - cyclizations - catalysis

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