Gold(I)-Catalyzed Intermolecular Aryloxyvinylation with Acetylene Gas

Abstract

Acetylene gas is an important feedstock for chemical production, although it is underutilized in organic synthesis. We have developed an intermolecular gold­(I)-catalyzed alkyne/alkene reaction of o-allylphenols with acetylene gas that gives rise to chromanes by a stereospecific aryloxycyclization through the nucleophilic regioselective opening of cyclopropyl gold­(I)-carbene intermediates. The synthetic application of this method was demonstrated in the late-stage functionalization of the natural product lapachol.

Three-Component Gold(I)-Catalyzed Alkoxyvinylation

“…In spite of these highly desired attributes of acetylene, the current industrial applications encompass uncatalyzed vinylation and hydrochlorination processes . Despite recent advances in the development of transition metal mediated methodologies, − more examples are desired for the full utilization of the intriguing properties of acetylene.…”

“…Even though there are several intermolecular examples in the literature (such as the [2 + 2] cycloaddition of alkenes and alkynes), , a majority of the reported examples are intramolecular (such as the cyclization of 1,n-enynes). , We have previously reported the successful gold­(I)-catalyzed reaction between acetylene gas and alkenes to perform ( Z , Z )-1,3-diene formations and biscyclopropanations, through ligand-controlled product distribution (Scheme a) . Additionally, we recently showed that, by including an O -nucleophile tethered to the alkene, the corresponding cyclopropyl gold­(I)-carbene intermediate could be trapped to afford 3-vinyl chromane scaffolds, including one of the first examples of enantioselective catalysis using acetylene gas (Scheme b) . In these studies we found that overactivity toward polymerization was a major issue to overcome, as the products of the reaction also contain alkenes which can again partake in the reaction to generate oligomeric products.…”

“…Inspired by the formation of pyrrolidine 7 and our previous synthesis of chromanes, we attempted the intramolecular trapping of the cyclopropyl gold­(I)-carbene by an amine nucleophile to afford 3-vinyl N -heterocycles (Scheme b). We decided to screen N -protecting groups as the reaction of free amine 8a did not yield any desired reactivity.…”