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.