Gold-catalyzed carbocyclization and imidization of alkyne-tethered diazo compounds with nitrosoarenes for the synthesis of nitrones and naphthalene derivatives

Abstract

A gold-catalyzed carbocyclization/imidization cascade reaction has been developed,leading a facile access to the synthesis of functionalized nitrones in moderate to good yields under mild conditions. The reaction initiated by a catalytic 6-endo-dig diazo-yne carbocyclization to form the key endocyclic vinyl carbene from alkyne-tethered diazo compounds, followed by addition with nitrosoarenes that features an imidization process. Notably, these resulting nitrone products could be smoothly converted into different substituted naphthalenol analogues, such as 4-aminonaphthalen-1-ol, naphthalene-1,4-dione, and naphthalene-1,4-diol derivatives, in high yields. Moreover, the generated products exhibited potential tumor suppression activity in tested cancer celllines; compound 3c (HCT116 cells, IC₅₀ = 7.41 μM; MCF-7 cells, IC₅₀ = 14.28 μM) exhibits higher anticancer potency than other tested compounds.

Keywords: Alkyne functionalization; Cascade reaction; Gold catalysis; Metal carbene.