Conversion of phenols to phosphamides and sulfonamides through a sequential dearomative functionalization and reductive coupling strategy

Abstract

An 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 involved the use of azides or amines as a nitrogen source, which have sensitivity and toxicity issues and might generate undesirable impurities in API synthesis. Here, a phenol was dearomatized using the hypervalent iodine reagent PhI(OAc)₂ to generate a p-quinone monoacetal, which was further condensed with a hydroxylamine to produce a common intermediate, a nitrosobenzene derivative. Nucleophiles like phosphine oxides and sodium arylsulfinates reacted smoothly with nitrosobenzene through reductive coupling to derive a series of arylphosphamide and arylsulfonamide scaffolds. The mechanistic studies revealed the role of the NaHSO₃ reductant during the generation of N–P and N–S bonds.