Hydro- and deutero-deamination of primary amines using O-diphenylphosphinylhydroxylamine

Abstract

While selective defunctionalizations are valuable in organic synthesis, hydrodeamination of primary amines poses challenges. Deuterodeamination, analogous to hydrodeamination, presents even greater difficulties due to its frequently slower deuteration rate, interference by hydrogenation and constraints in deuterated sources. This study introduces a reliable, robust, and scalable hydro- and deuterodeamination method capable of handling various primary amines. Defined by its mild reaction conditions, rapid completion, simplified purification facilitated by water-soluble byproducts, the method leverages deuterium oxide as a deuterium source and employs commercialized O-diphenylphosphinylhydroxylamine for deamination. Applied to a diverse range of biologically active molecules, it has consistently achieved high yields and efficient deuterium incorporation. By synergizing with site-selective C–H functionalization of primary aliphatic amines, our method reveals synthetic strategies utilizing nitrogen atom as a traceless directing group, encompassing deaminative alkylation, 1,1-deuteroalkylation, 1,1-dialkylation, 1,1,1-deuterodialkylation, C–H arylation, and 1,3-deuteroarylation. Emphasizing this innovation, the processes of deaminative degree-controlled deuteration have been developed.