Enantioselective synthesis of α-methyl carboxylic acids from readily available starting materials via chemoenzymatic dynamic kinetic resolution
2010 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 75, no 20, 6842-6847 p.Article in journal (Refereed) Published
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%.
Place, publisher, year, edition, pages
2010. Vol. 75, no 20, 6842-6847 p.
IdentifiersURN: urn:nbn:se:su:diva-45772DOI: 10.1021/jo1011653ISI: 000282604900012OAI: oai:DiVA.org:su-45772DiVA: diva2:369622
FunderKnut and Alice Wallenberg Foundation