Synthesis of amionophosphonic acid derivatives

Abstract

Exhaustive attempts have been made to carry out catalytic asymmetric hydrophosphonylation of aromatic imines with dialkyl phosphite. The use of various Lewis acid catalysts resulted in the desired product in fair to good yields. However, no enantioselectivity was observed in the product. An alternative chiral auxiliary-controlled synthesis with (S)-phenylglycinol as an auxiliary afforded the corespounding product with good diastereoselectivity. In the best case, the major to minor diastereomers ratio was 88:12. The selectivity was proposed to be due partly to intramolecular H-bonding interaction in the substrate. In addition, facile synthetic methods of diethyl N-Boc-1-aminoalkyl phosphonates have been developed. The procedures involve base-catalyzed addition of diethyl phosphite to N-Boc imine generated in situ by the reaction of a suitable base on α-amido sulfones. Among a variety of base, 1,8 diazabicyclo [5,4,0] undec-7-ene (DBU) in THF gave the best yields for aromatic sulfones in short time. For aliphatic counterparts, K2CO3 in CH3CN provided high yields in 2 days. Other N-substitited substrates of α-amido sulfones also gave high yields. Hydrolysis of the N-Boc-1-aminoalkylphosphonates to remove the Boc group and diethyl ester resulted in a high yield of α-aminophosphonic acids.