Highly Efficient Synthesis of Tri- and Tetrasubstituted Conjugated Enynes from Brønsted Acid Catalyzed Alkoxylation of 1-Cyclopropylprop-2-yn-1-ols with Alcohols

Abstract

A highly efficient triflic acid catalyzed ring opening of a wide variety of 1-cyclopropyl-2-propyn-1-ols with alcohols as an efficient synthetic route to conjugated enynes is reported herein. The reaction was operationally straightforward and accomplished in good to excellent yields (44-100%), high product turnovers (up to 10,000), and with complete regioselectivity under mild conditions with a low catalyst loading of 0.01 mol %. The mechanism is suggested to involve protonation of the alcohol substrate by the TfOH catalyst, followed by ionization of the starting material. This causes ring opening of the cyclopropane moiety and trapping by the alcohol nucleophile to give the conjugated enyne product. The synthetic utility of the present method was also exemplified by the efficient large-scale conversion in gram quantities of one example studied in this work to the corresponding conjugated enyne product in excellent yield and turnover number.