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

Organic Chemistry Frontiers Pub Date: 2021-12-17 DOI: 10.1039/D1QO01643A

Abstract

An unprecedented Ag(I)-catalyzed [3 + 3]-annulation of alkynyl alcohols (5-hexyn-1-ols) and α,β-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.

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