| Abstract
| - A high-yielding cross-coupling reaction of unactivated alkyl bromides possessing β-hydrogens withalkylzinc halides utilizing a Pd/N-heterocyclic carbene (NHC) catalyst at room temperature isdescribed. A variety of Pd sources, Pd2(dba)3, Pd(OAc)2, or PdBr2, with the commercially availableligand precursor 1,3-bis(2,6-diisopropylphenyl)imidazolium chloride (IPr·HCl) successfully coupled1-bromo-3-phenylpropane with n-butylzinc bromide in THF/NMP. An investigation of different NHCprecursors showed that the bulky 2,6-diisopropylphenyl moiety was necessary to achieve highcoupling yields (75−85%). The corresponding ethyl analogue was moderately active (11%). A rangeof unsymmetrical NHC precursors were prepared and evaluated. The ligand precursor containingone 2,6-diisopropylphenyl and one 2,6-diethylphenyl afforded the coupling product in 47% yield,clearly suggesting a direct relationship between the steric topography created by the flankingN-substituents and catalyst activity. Under optimal conditions, a number of alkyl bromides andalkylzinc halides possessing common functional groups (amide, nitrile, ester, acetal, and alkyne)were effectively coupled (61−92%). It is noteworthy that β-substituted alkyl bromides and alkylzinchalides successfully underwent cross-coupling. Also, under these conditions alkyl chlorides wereunaffected.
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