Defluorinative [4+1] annulation of perfluoroalkyl N-mesylhydrazones with primary amines provides 5-fluoroalkyl 1,2,3-triazoles

Fluoroalkyl 1,2,3-triazoles have great potential as medicinal chemistry building blocks. However, only a few synthetic routes to these compounds are currently available. Herein, we report on a novel method to access 5-fluoroalkyl 1,2,3-triazoles from easily prepared bench-stable perfluoroalkyl N-mesylhydrazone (PFHZ-Ms), a reagent that can transform amines to 5 fluoroalkyl 1,2,3-triazoles via defluorinative [4 + 1] annulation. The simple reaction protocol can be applied to a variety of amines containing a range of functional groups, delivering 1,2,3-triazoles in good to excellent yield. The utility of this method was demonstrated in the late-stage modification of bioactive molecules.

Automated summary

A novel method for accessing 5-fluoroalkyl 1,2,3-triazoles from easily prepared PFHZ-Ms has been reported, showing good to excellent yields in the synthesis of 1,2,3-triazoles and applicability to a variety of amines. This method's utility was demonstrated in the late-stage modification of bioactive molecules.