2. Alternative Mechanistic Explanation for Ligand-Dependent Selectivities in Copper-Catalyzed N- and O-Arylation Reactions

Yu, H.-Z.; Jiang, Y.-Y.; Fu, Y.;* Liu, L.  J. Am. Chem. Soc. 2010, 132, 18078–18091. Download Link

Abstract: The ligand-dependent selectivities in Ullmann-type reactions of amino alcohols with iodobenzene by β-diketone- and 1,10-phenanthroline-ligated CuI complexes were recently explained by the single-electron transfer and iodine atom transfer mechanisms (Jones, G. O.; Liu, P.; Houk, K. N.; Buchwald, S. L. J. Am. Chem. Soc. 2010, 132, 6205.). The present study shows that an alternative, oxidative addition/reductive elimination mechanism may also explain the selectivities. Calculations indicate that a CuI complex with a negatively charged
-diketone ligand is electronically neutral, so that oxidative addition of ArI to a
-diketoneligated CuI prefers to occur (and occur readily) in the absence of the amino alcohol. Thus, coordination of the amino alcohol in its neutral form can only occur at the CuIII stage where N-coordination is favored over O-coordination. The coordination step is the rate-limiting step and the outcome is that N-arylation is favored with the β-diketone ligand. On the other hand, a CuI complex with a neutral 1,10-phenanthroline ligand is positively charged, so that oxidative addition of ArI to a 1,10-phenanthroline-ligated CuI has to get assistance from a deprotonated amino alcohol substrate. This causes oxidative addition to become the rate-limiting step in the 1,10-phenanthroline-mediated reaction. The immediate product of the oxidative addition step is found to undergo facile reductive elimination to provide the arylation product. Because O-coordination of a deprotonated amino alcohol is favored over N-coordination in the oxidative addition transition state, O-arylation is favored with the 1,10-phenanthroline ligand.