A Study of factors affecting alpha-(N-carbamoyl)alkylcuprate chemistry.
The effect of Cu(I) salt (i.e., CuCN, CuCN.2LiCl, CuI), cuprate reagent, sec-butyllithium quality, solvent, and temperature upon the chemical yields obtained in the reactions of alpha-(N-carbamoyl)alkylcuprates [i.e., N-Boc-protected alpha-aminoalkylcuprates] with (E)1-iodo-1-hexene, 5,5-dimethyl-2-cyclohexenone, methylvinyl ketone, crotonate esters, and an acid chloride has been examined. Cuprate conjugate addition and vinylation reactions can succeed with low-quality sec-butyllithium, presumably containing insoluble lithium hydride and lithium alkoxide impurities, although yields are significantly lower than those obtained with high-quality s-BuLi. alpha-(N-Carbamoyl)alkylcuprates prepared from high-quality sec-butyllithium are thermally stable for 2-3 h at room temperature and are equally effective when prepared from either insoluble CuCN or THF-soluble CuCN.2LiCl. Use of the latter reagent permits rapid cuprate formation at -78 degrees C, thereby avoiding the higher temperatures required for cuprate formation from THF-insoluble CuCN that are problematic with solutions containing thermally unstable alpha-lithiocarbamates.
Hunter Laboratory, Department of Chemistry, Clemson University, Clemson, South Carolina 29634-1905, USA. dieterr@clemson.edu
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