I've tried making this compound from 3-oxo-2-phenylbutanenitrile and 2-(iodomethyl)-3-vinyloxirane under various conditions, with various bases. Tried it with HMPA and tBuLi first but formed the kinetic enolate and thus got the wrong regiochemistry. Then I tried (without HMPA) triethylamine, cesium carbonate, sodium phosphate, potassium tert-butoxide, and TBD, but none of those worked either. Mostly the enolate opened the epoxide rather than displacing the bromine. I then tried the catalytic Finkelstein reaction in acetone, but that did not seem to work either. (epoxide still opened) Maybe there is another route?
I think it might be easier to make the epoxide last rather than carry it through the earlier reactions. Here is a sequence that brings three pieces together. I suggest trying simply NaH in THF for the initial reaction (M = Na); trapping the alkoxide with MsCl should be straightforward , then acetal hydrolysis before workup should only require a small excess (say 2-5 eq) of water, with a drop of methanesulfonic acid to catalyze this reaction. Vinyl Grignard reagent addition should be done cold (at or below -78 C) to avoid nitrile reaction, then give the epoxide (you might use a pinch of dry 9,10-phenanthroline indicator and titrate the C2H3MgBr addition, then stir at room temp overnight.)
By the way, be careful with several reagents you're using. In particular, DMPU ( 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone) can often be substituted for HMPA, an established carcinogen. All epoxides should also be handled with care.
Thanks for the answer @James Kilgore. We always take due care with all reagents, of course.
Oops - you may have noticed I left out a carbonyl group - instead of methyl it should be acetyl (CH3COCH(Ph)CN, not CH3CH(Ph)CN) in the starting compound and subsequent products. Please substitute this scheme.
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