Synthesis of Enantiomers of Some Aminophosphonate Derivatives

Abstract

Raccmic diethyl α-(3,5-di-teri-butyl-4-hydroxyphenyl)-N-(arylakyl)aminomethylphosphonates 1 have been demonstrated 10 possess potent cholesterol lowering and antioaxidant activities in the mouse and dog [1], therefore it is of interest to determine if this pharmacological effect is due to one of its individual enantiomers. We wish to report the synthesis of enamtiomer pairs of the key primary amine 4. Condensation of 3,5-di-teri-butyl-4-hydroxybenzaldehyde with R(+)- and S(-)-α-methylbenzylamine gave the corresponding imine 2 to which was added diethyl phosphite. In each case, the major diastereomer of the aminoposphonates 3 formed were purified by crystallization and catalytically hydrogenated to yield an optically active primary aminophosphonate 4 in agreement with the literature [2][3], it was found that the major diastercomer 3 obtained from R(+)-α-methylbenzylamine gave, on hydrogenation, the levorotatory enantiomer 4 while the major diastereomer 3 from S(-)-α-methybenzylamine yielded the dextrorotatory isomer 4 ([α]_0–22-12.12° (c 165 CHCl₃) and [α]_0–22+11 32° (c 1.71.CHCl₃).