Copper-Catalyzed [4+2]-Cycloadditions of Isoxazoles with 2‑Alkynylbenzaldehydes To Access Distinct α‑Carbonylnaphthalene Derivatives: C(3,4)- versus C(4,5)-Regioselectivity at Isoxazoles

Cu­(II)-catalyzed [4+2]-cycloadditions occur between Cu–benzopyryliums and substituted isoxazoles with the regioselectivity on the C­(3,4)-carbons of isoxazoles. We postulate that a prior coordination of isoxazoles with Cu­(OAc)2 increases the π-bond character of the C­(3,4) carbons to become an effective 2π-donor. In this reaction sequence, 3,5-disubstituted isoxazoles yield α,γ-dicarbonylnaphthalenes whereas, 5-substituted isoxazoles deliver α,γ-dicarbonyl-β-aminonaphthalenes. For unsubstituted isoxazole, its cycloaddition chemoselectivity is switched to the C­(4,5)-addition regioselectivity to yield α-carbonyl-γ-cyanonaphthalene derivatives.