A silver-catalyzed [3+3]-annulation cascade of alkynyl alcohols and α,β-unsaturated ketones for the regioselective assembly of chromanes

An unprecedented Ag(i)-catalyzed [3 + 3]-annulation of alkynyl alcohols (5-hexyn-1-ols) and alpha,beta-unsaturated ketones is reported to construct simple to complex chromanes. This transformation begins with hydroalkoxylation of alkynol through C-C triple bond activation to give cyclic-enol ether, followed by intermolecular 1,4-addition and intramolecular 1,2-addition of enol ethers onto the enone and oxidative aromatization or Grob-type elimination steps. Facile reaction conditions, broad substrate scope, good to excellent yields, and atom economy are the salient features of this protocol. Isolation of the active pyran-tethered cyclohexadiene reaction intermediate, additional supporting experiments, and DFT calculations strongly support the experimental findings and corroborate our proposed mechanism.

Automated summary

An unprecedented Ag(i)-catalyzed [3 + 3]-annulation of alkynyl alcohols and alpha,beta-unsaturated ketones is reported for constructing chromanes, featuring facile reaction conditions, broad substrate scope, and good to excellent yields. Experimental findings, supported by isolation of reaction intermediate and DFT calculations, corroborate the proposed mechanism.