Phospha-Mannich reactions of phosphinous acids R₂P–OH and their derivatives

Abstract

Secondary phosphine oxides R₂P(O)H are a relatively stable tautomeric form of secondary phosphinous acids R₂P–OH that with imine/iminium species, or their donors, form compounds with a P(O)–C_sp3–N linkage (the phospha-Mannich reaction). These can be referred to as (α-aminoalkyl)phosphine oxides, (α-phosphinoylalkyl)amines, or P(O),N-acetals. Compared to P–C_sp3–N linkages of P,N-acetals, products of phospha-Mannich reactions involving secondary phosphines R₂PH, the P(O)–C_sp3–N linkage is significantly more stable that allows for many examples of α-functionalized P(O),N-acetals and α-phosphinoylated N-heterocycles, whereas such examples for P,N-acetals are rare. Trivalent derivatives of phosphinous acids such as halides R₂P–Hal, esters R₂P–OR’ (phosphinites), amides R₂P–NR’₂ (aminophosphines), and phosphides R₂P–PR’₂ (biphosphines) also participate in Mannich-type reactions with mechanisms depending on the reactants. The phosphinous halides and esters react with (α-alkoxyalkyl)amines (N,O-acetals) and (α-haloalkyl)amines (N,Hal-acetals), respectively, via Arbuzov-type intermediates that are rearranged into P(O),N-acetals and alkyl halides (Arbuzov rearrangement). Furthermore, unlike phospha-Mannich reactions involving phosphines, secondary phosphine oxides and P(O),N-acetals are less sensitive to oxidation, and imines/iminium species can be generated not only under conventional Mannich conditions, i.e., from N,E-acetals (E = OH, O, N, halogen, etc.), but also, for example, by oxidation of α-C-atom of amines, or by oxidation of alcohols to aldehydes that than form imines/iminium species with amines.

Graphical abstract

Keywords:

• Secondary phosphine oxides
• phosphinous acids
• α-aminoalkylphosphine oxides
• heterocycles
• acetals
• amines
• imines
• iminium salts
• condensation
• hydrophosphinoylation
• Kabachnik-Fields reaction
• Pudovik reaction

Acknowledgments

The author thanks Drs. Yulia B. Malysheva and Elena A. Zaburdaeva from the Nizhniy Novgorod State University, and Dr. Vladimir Malakhov from Ludwig-Maximilians-Universität München, for their help in the literature search.