Enantioselective Synthesis of α-Methyl Carboxylic Acids from Readily Available Starting Materials via Chemoenzymatic Dynamic Kinetic Resolution
journal contributionposted on 15.10.2010 by Lisa K. Thalén, Anna Sumic, Krisztián Bogár, Jakob Norinder, Andreas K. Å. Persson, Jan-E. Bäckvall
Any type of content formally published in an academic journal, usually following a peer-review process.
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%.