Enantioselective synthesis of α-fluorinated β-amino acid derivatives by an asymmetric mannich reaction and selective deacylation/ decarboxylation reactions

Abstract

A study was conducted to demonstrate enantioselective synthesis of α-fluorinated β-amino acid (AA) derivatives by an asymmetric Mannich reaction and selective deacylation or decarboxylation reactions. Better yield was obtained from the Mannich reaction between α-fluoro-β-ketoester and N-ethoxycarbonyl imine under the preliminary studies. The performance of β-keto acetyloxazolidinone was evaluated with a series of different N-Eoc imines in the presence of 10 mol% of bicyclic guanidine catalyst after establishing optimized conditions. Better results were observed with imines containing both electron-withdrawing and electron-donating aryl groups. The study focused on preparing α-fluoro-β-sulfones to determine their potential for the reaction. The Mannich reaction of 1-fluoro-1-(phenylsulfonyl) propan-2-α-fluoro-β-sulfones gave an adduct with a high ee value and good diastereoselectivity.