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A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
Published on: February 16, 2020
Enzyme-catalyzed enantioselective diaryl ketone reductions
Matthew D Truppo1, David Pollard, Paul Devine
1Department of Process Research, Merck Research Laboratories, Merck & Co., Inc., P.O. Box 2000, Rahway, New Jersey 07065, USA. matthew_truppo@merck.com
Organic Letters
|January 16, 2007
Summary
Chiral diarylmethanols are synthesized using ketoreductase enzymes (KREDs) with high yield and enantioselectivity. This biocatalytic method offers an efficient alternative to chemical catalysts for producing valuable chiral compounds.
Area of Science:
- Biocatalysis and Organic Synthesis
- Enzyme Engineering and Applications
Background:
- Diarylmethanols are important chiral building blocks in pharmaceuticals and fine chemicals.
- Traditional synthesis often relies on chemical catalysts, which can require harsh conditions and may lack selectivity.
- Ketoreductase enzymes (KREDs) offer a promising biocatalytic alternative for asymmetric synthesis.
Purpose of the Study:
- To explore the efficacy of ketoreductase enzymes (KREDs) for the asymmetric reduction of substituted benzophenone and benzoylpyridine derivatives.
- To evaluate the impact of various substitution patterns on enzyme selectivity and product yield.
- To demonstrate a biocatalytic route for synthesizing chiral diarylmethanols with high enantiomeric excess (ee).
Main Methods:
- Screening and application of various ketoreductase enzymes (KREDs).
- Reduction of a diverse library of substituted benzophenone and benzoylpyridine derivatives.
- Analysis of reaction products for yield and enantiomeric excess (ee) using analytical techniques.
Main Results:
- High yields (>90%) and excellent enantioselectivity (up to >99% ee) were achieved for the synthesis of chiral diarylmethanols.
- Substrates included ortho, meta, and para substituted derivatives with electron-donating, electron-withdrawing, and halogen groups.
- Effective reduction was observed without the need for ortho-substitution or highly electronically dissymmetric molecules, unlike conventional chemical methods.
Conclusions:
- Ketoreductase enzymes (KREDs) provide a highly efficient and selective biocatalytic method for synthesizing chiral diarylmethanols.
- This enzymatic approach overcomes limitations associated with traditional chemical catalysis, offering broader substrate scope and superior selectivity.
- The study highlights the potential of KREDs in green chemistry for the production of enantiomerically pure compounds.
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