Journal of Organic Chemistry
A three-step domino reaction between 1-aryl-3-hexyne-2,6-diol derivatives and aldehydes is used to construct tricyclic 1,4-dihydro-2H-benzo[f]isochromenes. The cascade is initiated by BF3·OEt2 and involves alkynyl-Prins cyclization, Friedel–Crafts alkenylation, and dehydration/aromatization to create a new, central aromatic ring and eliminate 2 equiv. of water. Electron-donating substituents on the aryl ring of the 1-aryl-3-hexyne-2,6-diols significantly increase overall yields as do electron-rich aldehyde reaction partners. For 2,4-disubstituted 2H-benzo[f]isochromene products, diastereoselectivities in the alkynyl-Prins reaction are ∼1.4 : 1 in favor of the cis-diastereomer. The stereochemistry of one cis-product was verified by X-ray crystallographic analysis and a second structure was also verified by X-ray analysis.
Hinkle, Robert J. and Lewis, Shane E., Atom Economical, One-Pot, Three-Reaction Cascade to Novel Tricyclic 2,4-Dihydro-1H-benzo[f]isochromenes (2013). Journal of Organic Chemistry.