A Highly Stereospecific Claisen-Sakurai Approach to Densely Functionalized Cyclopentenols
Ksenia S. Stankevich and Matthew J. Cook*
*Department of Chemistry and Biochemistry, Montana State University, Bozeman, Montana 59717, United States,
Email: mcook03
amgen.com
K. S. Stankevich, M. J. Cook, J. Org. Chem., 2022, 87, 12250-12256.
DOI: 10.1021/acs.joc.2c01397
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Abstract
The use of a Claisen-Sakurai reaction in a one-pot sequence provides highly substituted cyclopentenols in high stereoselectivity. The stereochemical outcome is defined by a combination of Claisen stereospecificity and stereoelectronic effects in the Sakurai cyclization that promotes reactivity via an anti-SE' antiperiplanar transition state.
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proposed reaction pathway
Stepwise Claisen-Sakurai reaction
To an oven dried round bottom flask equipped with reflux condenser and magnetic stirrer bar and purged with nitrogen was added desired allyl vinyl ether (1.00 equiv.). Dry chlorobenzene was added (0.05 M) and the temperature was raised to 70, 90 or 110 ºC depending on the substrate using heating mantle. Once reaction was complete by TLC, the reaction mixture was cooled to 20 ºC and aluminuim trichloride (1.50 equiv.) was added in a single portion. The reaction was allowed to stir for 30 minutes at 20 ºC. The reaction mixture was diluted with ether and cooled to 0 ºC. Water (0.04x mL) was added and stirred for 5 minutes, followed by the sequential addition of NaOH (15%(aq), 0.04x mL) and water (0.1x mL) [where x is amount of mmol of aluminium trichloride]. The mixture was warmed to room temperature, strirred for 45 min, the white precipitate was filtered and the filtrate concentrated in vacuo. The crude product was purified by column chromatography.
Key Words
Claisen Rearrangement, Hosomi-Sakurai Reaction, Cyclopentenes, Cyclopentanols
ID: J42-Y2022
