Enantioselective Synthesis of α-Methyl Carboxylic Acids from Readily Available Starting Materials via Chemoenzymatic Dynamic Kinetic Resolution

An enantioselective method for the synthesis of α-methyl carboxylic acids starting from trans-cinnamaldehyde, a readily available and inexpensive compound, has been developed. Allylic alcohol 1 was obtained via a standard Grignard addition to trans-cinnamaldehyde. Dynamic kinetic resolution was appl...

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Bibliographic Details
Published in:Journal of organic chemistry 2010-10, Vol.75 (20), p.6842-6847
Main Authors: Thalén, Lisa K, Sumic, Anna, Bogár, Krisztián, Norinder, Jakob, Persson, Andreas K. Å, Bäckvall, Jan-E
Format: Article
Language:English
Subjects:
Acrolein - analogs & derivatives
Acrolein - chemistry
Bioconversions. Hemisynthesis
Biological and medical sciences
Biotechnology
Carboxylic Acids - chemical synthesis
Carboxylic Acids - chemistry
Catalysis
Catalysts: preparations and properties
Chemistry
Exact sciences and technology
Fundamental and applied biological sciences. Psychology
Fungal Proteins
General and physical chemistry
Kemi
Kinetics
Lipase - chemistry
Lipase - metabolism
Methods. Procedures. Technologies
Molecular Structure
NATURAL SCIENCES
NATURVETENSKAP
Organic chemistry
Organisk kemi
Organometallic Compounds - chemistry
Peptide Hydrolases - chemistry
Peptide Hydrolases - metabolism
Propanols - chemical synthesis
Propanols - chemistry
Stereoisomerism
Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry
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Summary:An enantioselective method for the synthesis of α-methyl carboxylic acids starting from trans-cinnamaldehyde, a readily available and inexpensive compound, has been developed. Allylic alcohol 1 was obtained via a standard Grignard addition to trans-cinnamaldehyde. Dynamic kinetic resolution was applied to allylic alcohol 1 utilizing a ruthenium catalyst and either an (R)-selective lipase or an (S)-selective protease to provide the corresponding allylic esters in high yield and high ee. A copper-catalyzed allylic substitution was then applied to provide the corresponding alkenes with inversion of stereochemistry. Subsequent C−C double bond cleavage afforded pharmaceutically important α-methyl substituted carboxylic acids in high ee and overall yields of up to 76%.
ISSN:0022-3263
1520-6904
1520-6904
DOI:10.1021/jo1011653