Direct Synthesis of Amides from Benzonitriles and Benzylic Alcohols via a KOt-Bu-Mediated MPV-type Hydrogen Transfer Process

Abstract

Meerwein−Ponndorf−Verley (MPV)-type reduction between benzonitriles and benzylic alcohols under transitionmetal-free conditions has been demonstrated for the first time. Using simple KOt-Bu as the base, various benzonitriles can be efficiently reduced by benzylic alcohols via hydrogen transfer reduction, and the resultant phenyl imine can react further with benzylic alcohols to give amides as the final product in which both the alcohols and the nitriles are incorporated. Preliminary mechanistic investigations indicated that the reaction may go through multiple MPV-type hydrogen transfer processes.

A Short Synthesis of Ergot Alkaloids and Evaluation of the 5-HT1/2 Receptor Selectivity of Lysergols and Isolysergols

“…Condensation of indole 4 with 6 furnishes conjugated imine 7 . Hydride transfer − from another equivalent of Cs - 3b provides tautomer 5b′ and final product 5b as well as an equivalent of 6 to continue the chain process. Previous studies required additives to promote the MPV-type reduction of intermediate adducts. − However, the reaction seems to proceed catalytically using oxygen in air as the initial oxidant.…”

“…Hydride transfer − from another equivalent of Cs - 3b provides tautomer 5b′ and final product 5b as well as an equivalent of 6 to continue the chain process. Previous studies required additives to promote the MPV-type reduction of intermediate adducts. − However, the reaction seems to proceed catalytically using oxygen in air as the initial oxidant. Further mechanistic studies and investigations of the scope and limitations of the Cs 2 CO 3 -mediated HA reaction are currently in progress.…”