Conversion of Phenols to Phosphamides and Sulfonamides through a Sequential Dearomative Functionalization followed by Reductive Coupling Strategy

Abstract

Efficient and direct conversion of phenols to arylphosphamides and arylsulfonamides has been achieved using a sequential oxidative dearomative functionalization-reductive coupling strategy. The earlier methods involve use of azides or amines as nitrogen source that have sensitivity and toxicity issues and might generate undesirable impurities in API synthesis. Here, phenol was dearomatized using hypervalent iodine reagent PhI(OAc)2 to generate a p-quinone monoacetal, which was further condensed with hydroxylamine to produce a common intermediate, nitrosobenzene derivative. Nucleophiles like phosphine oxide and sodium arylsulfinate were reacted smoothly with nitrosobenzene through a reductive coupling to derive a series of arylphosphamide and arylsulfonamide scaffolds. The mechanistic studies reveal the role of NaHSO3 reductant during the generation of N-P and N-S bonds.