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. 2010 May 5;132(17):6205-13.
doi: 10.1021/ja100739h.

Computational explorations of mechanisms and ligand-directed selectivities of copper-catalyzed Ullmann-type reactions

Gavin O Jones  1 , Peng Liu, K N Houk, Stephen L Buchwald
Affiliations

Computational explorations of mechanisms and ligand-directed selectivities of copper-catalyzed Ullmann-type reactions

Gavin O Jones et al. J Am Chem Soc. .

Abstract

Computational investigations of ligand-directed selectivities in Ullmann-type coupling reactions of methanol and methylamine with iodobenzene by beta-diketone- and 1,10-phenanthroline-ligated Cu(I) complexes are reported. Density functional theory calculations using several functionals were performed on both the nucleophile formation and aryl halide activation steps of these reactions. The origin of ligand-directed selectivities in N- versus O-arylation reactions as described in a previous publication (J. Am. Chem. Soc. 2007, 129, 3490-3491) were studied and explained. The selectivities observed experimentally are derived not from initial Cu(I)(nucleophile) complex formation but from the subsequent steps involving aryl halide activation. The arylation may occur via single-electron transfer (SET) or iodine atom transfer (IAT), depending on the electron-donating abilities of the ligand and nucleophile. Mechanisms involving either oxidative addition/reductive elimination or sigma-bond metathesis are disfavored. SET mechanisms are favored in reactions promoted by the beta-diketone ligand; N-arylation is predicted to be favored in these cases, in agreement with experimental results. The phenanthroline ligand promotes O-arylation reactions via IAT mechanisms in preference to N-arylation reactions, which occur via SET mechanisms; this result is also in agreement with experimental results.

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Figures

Figure 1
Figure 1
Computational models of reagents studied in N- and O-arylation reactions.
Figure 2
Figure 2
Reaction free energies in kcal/mol in solution for CuI(nucleophile) formation from the reactions between CuI(iodide) complexes 10 and 11 and the methanol or methylamine nucleophiles. Energies are given for reactions with methanol and methylamine, respectively.
Figure 3
Figure 3
Interactions of frontier molecular orbitals of 12, 13, 14 and 15 with the LUMO of iodobenzene.
Figure 4
Figure 4
Free energies of intermediates in IAT mechanisms involving intermediates 12, 13, 14 and 15. Energies are given for reactions with methanol and methylamine, respectively.
Figure 5
Figure 5
Free energies of intermediates in SET mechanisms involving intermediates (a) 12, 13 and (b) 14 and 15. Energies are given for reactions with methanol and methylamine, respectively.
Figure 7
Figure 7
Free energy profiles for (a) β-diketone and (b) phenanthroline-promoted CuI-catalyzed reactions of methanol and methylamine with iodobenzene. Energies are given for reactions with methanol and methylamine, respectively.
Scheme 1
Scheme 1
Scheme 2
Scheme 2
Scheme 3
Scheme 3
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References

    1. Ullmann F, Bielecki J. Chem. Ber. 1901;34:2174–2185.
    2. Ullmann F. Chem. Ber. 1903;36:2382–2384.
    3. Ullmann F, Sponagel P. Chem. Ber. 1905;38:2211–2212.
    4. Goldberg I. Chem. Ber. 1906;39:1691–1692.
    1. Shafir A, Buchwald SL. J. Am. Chem. Soc. 2006;128:8742–8743. - PubMed
    1. de Lange B, Lambers-Verstappen MH, Schmieder-van de Vondervoort L, Sereinig N, de Rijk R, de Vries AHM, de Vries JG. Synlett. 2006:3105–3109.
    1. Klapars A, Huang X, Buchwald SL. J. Am. Chem. Soc. 2002;124:7421–7428. - PubMed
    2. Antilla JC, Klapars A, Buchwald SL. J. Am. Chem. Soc. 2002;124:11684–11688. - PubMed
    1. Goodbrand HB, Hu NX. J. Org. Chem. 1999;64:670–674.

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