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-carbaramoyl)-alkylcuprates [i.e., N- Boc-protected alpha -aminoalkylcuprates] with (E)1-iodo-1-hexene, 5,5-dimet hyl-2-cyclohexenone, methylvinyl ketone, crotonate esters, and an acid chlo ride has been examined. Cuprate conjugate addition and vinylation reactions can succeed with low-quality sec-butyllithium, presumably containing insol uble lithium hydride and lithium alkoxide impurities, although yields are s ignificantly lower than those obtained with high-quality s-BuLi. alpha-(N-C arbamoyl)alkylcuprates prepared from high-quality sec-butyllithium are ther mally stable for 2-3 h at room temperature and are equally effective when p repared from either insoluble CuCN or THF-soluble CuCN 2LiCl. Use of the la tter reagent permits rapid cuprate formation at -78 degreesC, thereby avoid ing the higher temperatures required for cuprate formation from THF-insolub le CuCN that are problematic with solutions containing thermally unstable a lpha -lithiocarbamates.