A New Approach to the Efficient Method for the Asymmetric Synthesis of (S)-O-, M-, P-Fluorophenylalanines and Their 2-Methyl-substituted Analogs

Abstract

Abstract

The reactions of asymmetric C-alkylation of glycine and alanine in Ni^II complexes of their Schiff's bases with modified chiral auxiliaries (S)-2-N-[(N′-2-chlorobenzylprolyl)amino]benzophenone and (S)-2-N-[N′-(3,4-dimethylbenzylprolyl)amino]benzophenone by fluorine-substituted benzyl halogenides have been studied. As a result, a highly stereoselective and relatively rapid method for the asymmetric synthesis of (S)-o-, m-, p-fluorophenylalanines and their 2-methyl substituted analogs has been developed.

Keywords:

• Asymmetric synthesis
• c-alkylation
• chiral NiII complex
• fluorophenylalanine

ACKNOWLEDGMENT

This work was supported by ISTC Grants 2780 and A-1247.

Notes

^aReaction conditions: the reactions were run in DMF, concentration of initial complex was 1.4 M, ratio of the initial complex–alkylating agent–NaOH = 1:1.2:2.5, at 20–25 °C, under Ar.

^bChemical yield on the stage of alkylation (mixture of diastereomeric complexes).

^cData obtained by chiral HPLC analysis.

^aReaction conditions: the reactions were run in DMF, was concentration of initial complex 0.3 M, ratio of the initial complex–alkylating agent–NaOH = 1:3.5:5, at 20–25 °C, under Ar.

^bChemical yield on the stage of alkylation (mixture of diastereomeric complexes).

^cData obtained by chiral HPLC analysis.