Manufacture of optically active .alpha.-arylalkanoic acids and

Abstract

This invention concerns a new process of preparing optically active .alpha.-arylalkanoic acids and their precursors. These .alpha.-arylalkanoic acids, esters, amides, nitriles, oxazolines and metal salts are stereoselectively prepared by forming the metal or metal halide of the corresponding acid, ester, amide, oxazoline, nitrile, or metal salt and treating the compound so prepared with an aryl halide in the presence of a chiral (optically active) transition metal catalyst of the formula (LL*)QZT wherein Q is a transition metal selected from palladium and nickel; Z and T are independently halogen; and LL* is a chiral tertiary diphosphine compound capable of acting as a bidentate ligand with Q to form a 5-membered ring, optionally in the presence of a dipolar aprotic solvent or mixtures thereof, for a time sufficient to form the corresponding optically active .alpha.-arylalkanoic acid, ester, amide, nitrile, oxazoline or metal salt, and optionally concomitantly or sequentially hydrolyzing any ester, amide, nitrile, oxazoline or metal salt formed to the corresponding optically active .alpha.-arylalkanoic acid. The process optionally further includes removal of halogen atom from the aromatic portion of the .alpha.-arylalkanoic acid. The process optionally includes subsequent formation of the pharmaceutically acceptable salts and esters of the optionally active .alpha.-arylalkanoic acid. This is a simple process for the preparation of the described optically active .alpha.-arylalkanoic acids. These compounds are useful as pharmaceutical (e.g., anti-inflammatory) agents.