An Electroenzymatic Platform toward Enantioenriched α-Chloro- and α,α-Dichloro β-Hydroxy Esters

Area of Science:

• Organic Chemistry
• Biocatalysis
• Synthetic Chemistry

Background:

• Enantioenriched α-halo- and α,α-dihalo β-hydroxy esters are crucial synthons in medicinal chemistry.
• Existing synthesis methods often lack efficiency or enantioselectivity.

Purpose of the Study:

• To develop an efficient and enantioselective synthesis of α-chloro- and α,α-dichloro β-hydroxy esters.
• To utilize readily available β-keto esters as starting materials.

Main Methods:

• An electroenzymatic sequential platform was designed.
• The platform integrates electrochemical chlorination with enzymatic reduction.
• An engineered ketoreductase (AxSDR M3) was employed for catalysis.

Main Results:

• The protocol successfully synthesized enantioenriched α-chloro- and α,α-dichloro β-hydroxy esters.
• Isolated yields reached up to 74%.
• Excellent enantioselectivities were achieved, exceeding 99% ee.

Conclusions:

• The developed electroenzymatic platform provides a powerful strategy for accessing valuable chiral building blocks.
• This method offers a sustainable and efficient route for pharmaceutical ingredient synthesis.