Synthesis of α-aminophosphonates and related derivatives under microwave conditions

α-Aminophosphonates and related derivatives form one of the most important class of organophosphorus compounds due to their broad spectrum of biological activity. The most widely applied synthetic routes toward α‑aminophosphonates and α‑aminophosphine oxides is the Kabachnik-Fields (phospha-Mannich) reaction involving the condensation of an amine, an oxo compound and a >P(O)H species, such as dialkyl phosphite or secondary phosphine oxide. Etyl octyl phosphite and alkyl phenyl-H-phosphinates were also applied as the P‑reagent [1]. The other route is the Pudovik reaction of imines with >P(O)H species. An eco-friendly, solvent- and catalyst-free accomplishment for the synthesis of various α‑aminophosphonates was developed under microwave (MW) conditions starting from different primary or secondary amines. The phospha-Mannich reaction was also investigated in aqueous solution using triethyl phosphite as the P-reagent. Optically active derivatives were also obtained starting from (S)-α-phenylethylamine [2]. Bis(aminophosphonates) were synthesized by the double Kabachnik–Fields reaction. Furthermore, the synthesis of bis(aminophosphine oxides) was also studied starting from various secondary phosphine oxides [3]. After double deoxygenation, the bis-phosphines were utilized as bidentate P-ligands in the synthesis of cyclic platinum and palladium complexes. A facile catalyst- and solvent-free method was elaborated for the synthesis of amino-methylenebisphosphonates and amino-methylenebis(phosphine oxides) by the three-component MW-assisted condensation of an amine, an orthoformate and dialkyl phosphites or diphenyl phosphine oxides. Finally, a „green” accomplishment of the Pudovik reaction giving α‑aryl-α-aminophosphonate derivatives was performed.

References

[1]       Keglevich, G.; Szekrényi, A. Lett. Org. Chem. 2008, 5, 616.

[2]       Bálint, E.; Tajti, Á.; Kalocsai, D.; Mátravölgyi, B.; Karaghiosoff, K.; Czugler, M.; Keglevich, G. Tetrahedron, 2017, 73, 5659.

[3]       Bálint, E.; Tripolszky, A.; Jablonkai, E.; Karaghiosoff, K.; Czugler, M.; Mucsi, Z.; Kollár, L.; Pongrácz, P.; Keglevich G. J. Organomet. Chem. 2016, 801, 111.

[4]       Bálint, E.; Tajti, Á.; Ádám, A.; Csontos, I.; Karaghiosoff, K.; Czugler, M.; Ábrányi-Balogh, P.; Keglevich, G. Beilstein J. Org. Chem. 2017, 13, 76.