Biocatalyzed Enantioselective Reduction of Activated C=C Bonds: Synthesis of Enantiomerically Enriched α‐Halo‐β‐arylpropionic Acids

Abstract

The enantioselective biocatalyzed reduction of the C=C bond of some (Z)‐methyl α‐halo‐β‐arylacrylates was investigated. The reaction was performed by baker's yeast fermentation and Old Yellow Enzymes 1–3 mediated biotransformations. The final products were, respectively, enantiomerically enriched (S)‐α‐halo‐β‐arylpropionic acids and their methyl esters, and ester hydrolysis was promoted in the whole cell system. High conversions and enantioselectivity values were observed when the aromatic ring was substituted by an electron‐withdrawing group. Further manipulation of two of these enantiomerically enriched (S)‐haloacids afforded p‐substituted D‐phenylalanines.

Asymmetric bioreduction of activated alkenes to industrially relevant optically active compounds

“…Brenna and co-workers investigated the bioreduction of various methyl α-halo-β-substituted acrylates using isolated OYE1-3 and baker's yeast (Fig. 11) (Brenna et al, 2011b). OYE3 furnished the corresponding ( S )-products in good to excellent stereoselectivity ( ee  ≥ 88%).…”

Ene‐reductases and their Applications

“…However, the addition of a second activating group can increase the C═C bond polarization and facilitate the hydrogenation. Several studies have been performed on α,β-unsaturated dicarboxylic acids and esters [41,42] and α-halo-substituted unsaturated acids and esters [19,40,[43][44][45] for determining the reaction rate and/or stereochemical outcome of the asymmetric hydrogenation using ERs. For example, an additional halogenated substituent in the α-position was shown to be beneficial for ER activity, whereas β-alkyl or β-aryl substituents were detrimental for the reactivity of nonhalogenated substrates [40,43].…”

Advances in the Synthesis of Methylated Products through Indirect Approaches

“…Recently, the usage of an H 2 ‐[Pd] system in an alcoholic solvent has been reported . The application of Pd nanoparticles on a nanodiamond (ND) support for the hydrogenating deamination of benzonitrile, aromatic imines, and amines has been developed.…”