α,α-Difluoro-β-iminophosphonates, an alternative strategy towards the synthesis of α,α-difluoro-β-aminophosphonate derivatives?

New Journal of Chemistry Pub Date: 2017-06-15 DOI: 10.1039/C7NJ00997F

Abstract

α,α-Difluoromethylenephosphonates are generally known as stable natural phosphate mimics with significantly improved biological activities. A number of α,α-difluoroalkylphosphonates have already been found to be important enzyme inhibitors. Herein, we report an alternative strategy towards the synthesis of α,α-difluoromethylene-β-aminophosphonate derivatives. A small library of N-substituted α,α-difluoro-β-aminophosphonates was designed and described via NMR study. The protocol began with the condensation of β-ketophosphonates with a series of primary amines. The key step of the synthesis is an electrophilic fluorination, mediated by Selectfluor?, of the mixture of β-enamino/β-iminophosphonates leading to α,α-difluoro-β-iminophosphonates followed by reduction. The title compounds may behave as convenient building blocks for further more advanced modification.

Graphical abstract: α,α-Difluoro-β-iminophosphonates, an alternative strategy towards the synthesis of α,α-difluoro-β-aminophosphonate derivatives
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