Synthesis of 3-Cyano-1H-indoles and Their 2′-Deoxyribonucleoside Derivatives through One-Pot Cascade Reactions

An efficient and economical synthetic approach toward 3-cyano-1H-indoles through the reactions of 2-(2-bromophenyl)acetonitriles with aldehydes and aqueous ammonia is presented. Mechanically, this novel protocol involves a one pot cascade procedure consisting of an aldol-type condensation,. a copper-catalyzed amination by using aqueous ammonia as a cheap and safe nitrogen source, and an intramolecular Michael addition followed by a dehydrogenative aromatization. Interestingly, the indole products thus obtained were found to be ready substrates for the preparation of indole 2'-deoxyribonucleosides through an unprecedented and highly practical glycosylation procedure in which the required C-N bond formation and toluoyl protecting group removal were accomplished efficiently in one pot.