• 10.1139/v97-090
  • Canadian Journal of Chemistry
  • Volume 75
  • June 1997
  • pp 742-753

Reliable procedure but modifications helpful

Details


The article by Strunz and co-workers reported a total synthesis of sterpurene and the bioactivity of some related sesquiterpene metabolites.

I am particularly interested in the preparation of intermediate 14 (4-step synthesis, Scheme 3) since it could serve as a building block to my target molecule. The reported procedure is very reliable and the desried conjugated ester 14 was obtained smoothly. However, a few modifications were made to make the procedures easier to operate:

1) The first step (hydrogenation): I tested several solvents and found ethyl acetate gave the best yield. The ACS grade ethyl acetate was used as received and you do not have to pre-dry it.

2) The second step (carboxymethylation): potassium hydride was NOT necessary and only sodium hydride (40% in mineral oil) was employed as a deprotonation reagent.

3) The third step (Chlorination): since chlorine gas is toxic and hard to handle, a modified procedure was employed. To a solution of 2-carbomethoxy-4,4-dimethyl-1-cyclohexanone (2.39 g, 13.1 mmol) and PhSeCl (125 mg, 0.66 mmol) in CH3CN (25 mL) at room temperature was added N-Chlorosuccinimide (NCS) (1.92 g, 14.4 mmol). The resulting mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted between Et2O (100 mL) and H2O (30 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and evaporated. The residue was purified by silica gel column chromatography (EtOAc:hexanes = 1:20, Rf = 0.2) to give the desired product (2.75 g, 96% yield) as a yellow oil.

4) The last step: the solvent (xylenes) needed to pre-dry prior to use. A longer reaction time (3 days instead of 24 h reported in the paper) was employed to ensure the completion of the reaction. In addition, the product is volatile and therefore a distillation under atmospheric pressure was used to purify the product (54% yield vs 66% yield reported in the paper).



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