Continuous Flow Synthesis of Isoxazoles via Vinyl Azides from Friedel-Crafts Acylation of Alkynes: A Modulated Troubleshooting Optimization Approach.

The synthesis of isoxazoles has been achieved in a continuous flow system composed of two reaction units: the Friedel-Crafts acylation of alkynes and the azide conjugate addition to the resulting β-chlorovinyl ketones followed by a photochemical-thermal reaction sequence. The salient feature of the current flow system includes the safe handling of potentially explosive organic azide species as well as the rapid conversion of batch reactions into flow conditions with the integration of multiple reactor units.