Tunable Key [3+2] and [2+1] Cycloaddition of Enaminones and ?-Diazo Compounds for the Synthesis of Isomeric Isoxazoles: Metal-Controlled Selectivity

The three-component reactions of enaminones, alpha- diazo esters/ketones, and t-butyl nitrite (TBN) for the switchable synthesis of isomeric isoxazoles have been realized. The catalysis with Cu(II) salt provides 3,4-disubsituted isoxazoles via [3 + 2] cycloaddition. On the other hand, the catalysis of Ag(I) with identical substrates leads to isomeric isoxazoles with reversed C3 and C4 substitution based on a key [2 + 1] cycloaddition.

Automated summary

The switchable synthesis of isomeric isoxazoles has been achieved through three-component reactions of enaminones, alpha-diazo esters/ketones, and t-butyl nitrite (TBN). Catalysis with Cu(II) salt leads to 3,4-disubstituted isoxazoles via [3 + 2] cycloaddition, while catalysis with Ag(I) results in isomeric isoxazoles with reversed C3 and C4 substitution based on a key [2 + 1] cycloaddition.