Chemodivergent and diastereoselective synthesis of syn- and anti-cyclopentenyl spiroisoxazolones under ball-milling conditions

Abstract

A new cyclization pattern between arylidene isoxazolones and enamino esters has been demonstrated, efficiently affording various structurally novel cyclopentenyl spiroisoxazolones with high chemoselectivity in a ball mill. Interestingly, the diastereoselectivity of the spiro products is also controllable, with both syn- and anti-isomers generated selectively under different reaction conditions. The mechanochemical protocol features good chemo- and diastereoselectivity, high efficiency, mild reaction conditions and minimal solvent usage, providing rapid, environmentally benign and scalable access to spirocyclopentenes.