A Hydrido-Alkynyl-Prins Cyclization Using Isopropanol as Hydride Donor: Discovery, Scope and Mechanistic Study

Abstract

The Alkynyl-Prins cyclization is a very important strategy in organic synthesis for the construction of cyclic frameworks and natural products, via vinyl carbocation intermediate under acid catalysis. Surprisingly, the alternate Alkynyl-Prins cyclization (between an alkyne-tethered aldehyde/ketones and an external alcohol), has been less explored. Herein, we have designed and developed an unprecedented hydrido-Alkynyl-Prins cyclization, which involves an alternate Alkynyl-Prins cyclization, [1,5]-hydride migration, and SN2' nucleophilic substitution cascade. In this reaction various alcohols, such as isopropanol were employed as hydride donors. A broad scope has been observed for the alkyne-aldehydes and alcohols, for the construction of the corresponding, chromenes, 1,2-dihydroquinolines, and phenanthrenes, by respectively employing oxygen, nitrogen and carbon tethered alkyne-carbaldehydes. Performing an experiment with a deuterated sec-alcohol, and isolating the corresponding di-deuterated ether and ketone, supported the proposed mechanism involving a [1,5]-hydride migration. When the reaction was performed in the presence of H2O18, the enhanced yield of the ketone (58% from 13%) and presence of the O18 in it (HRMS-analysis) clearly suggested the formation of the ketone possibly via the competitive trapping of the vinyl carbocation by the water.