Phospha-Mannich reactions of RPH2, R2PH, and R3P

Phosphorus-based Mannich-type reactions (phospha-Mannich reactions) of primary or secondary phosphines with carbonyl compounds and amines (R2NH, RNH2, and NH3) provide a powerful synthetic tool in the worldwide search for future ligands. The variety of amines and phosphines available allows for designing and fine-tuning water-soluble, chiral, macrocyclic, pincer, tripodal, photoactive, and etc., phosphine ligands with P–C–N linkage(s) (P,N-acetals). Aminized supports and amine-terminated dendrimers can easily be phosphine-functionalized by phospha-Mannich reactions, and used in reusable heterogeneous catalysts. If CH2O is used as a C-component, its stable adducts with phosphines, that is, RP(CH2OH)2 and R2PCH2OH, are often used in syntheses of P,N-acetals as they are less toxic and non-pyrophoric analogs of the phosphines, whereas other carbonyl compounds are usually converted into imines or iminium salts. In phospha-Mannich reactions, tertiary phosphines form a P+–C–N linkage (P+,N-acetals) that can easily be broken by bases, realizing imine, or iminium cations, and are used as imine/iminium donors in organic syntheses.