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. 2011 Sep 14;133(36):14293-300.
doi: 10.1021/ja2012627. Epub 2011 Aug 23.

Two metals are better than one in the gold catalyzed oxidative heteroarylation of alkenes

Ekaterina Tkatchouk  1 , Neal P Mankad, Diego Benitez, William A Goddard 3rd, F Dean Toste
Affiliations

Two metals are better than one in the gold catalyzed oxidative heteroarylation of alkenes

Ekaterina Tkatchouk et al. J Am Chem Soc. .

Abstract

We present a detailed study of the mechanism for oxidative heteroarylation, based on DFT calculations and experimental observations. We propose binuclear Au(II)-Au(II) complexes to be key intermediates in the mechanism for gold catalyzed oxidative heteroarylation. The reaction is thought to proceed via a gold redox cycle involving initial oxidation of Au(I) to binuclear Au(II)-Au(II) complexes by Selectfluor, followed by heteroauration and reductive elimination. While it is tempting to invoke a transmetalation/reductive elimination mechanism similar to that proposed for other transition metal complexes, experimental and DFT studies suggest that the key C-C bond forming reaction occurs via a bimolecular reductive elimination process (devoid of transmetalation). In addition, the stereochemistry of the elimination step was determined experimentally to proceed with complete retention. Ligand and halide effects played an important role in the development and optimization of the catalyst; our data provides an explanation for the ligand effects observed experimentally, useful for future catalyst development. Cyclic voltammetry data is presented that supports redox synergy of the Au···Au aurophilic interaction. The monometallic reductive elimination from mononuclear Au(III) complexes is also studied from which we can predict a ~15 kcal/mol advantage for bimetallic reductive elimination.

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Figures

Figure 1
Figure 1
Transition structures 3, 5 and 9, including selected interatomic distances (Å) for the oxidative formation of binuclear Au species.
Figure 3
Figure 3
Cyclic voltammetry data: (a) oxidative scans for complexes 17 (solid) and 18 (dashed); (b) reductive scans for complexes 16 (solid) and 17 (dashed). Conditions: CH2Cl2 solvent, 0.1 M Bu4NPF6, 100 mV/s scan rate.
Figure 4
Figure 4
Transition structures for the bimolecular reductive elimination from a) mononuclear PPh3Au, b) binuclear [PPh3Au]2, and c) binuclear (dppm)Au2 complexes.
Figure 5
Figure 5
Selected molecular orbitals for key intermediate 12-dppm [(dppm)(AuCl)2F(Cyclized Substrate)].
Scheme 1
Scheme 1
Proposed pathways for the oxidative heteroarylation of alkenes. a) Proposed bimolecular reductive elimination pathway, and b) transmetalation/unimolecular reductive elimination pathway.
Scheme 2
Scheme 2
Mechanistic hypotheses for oxidation leading to a substrate coordinated binuclear complex.
Scheme 3
Scheme 3
Mechanistic hypothesis for aminoauration and bimetallic reductive elimination. Free energies at 298 K (ΔG298K) at M06/LACV3P**++(2f) level of theory.
Scheme 4
Scheme 4
Stereochemistry of C–C reductive elimination.
Scheme 5
Scheme 5
Revised mechanism for heteroarylation of alkenes catalyzed by dppm(AuBr)2.
See this image and copyright information in PMC

References

    1. Nicolaou KC, Bulger PG, Sarlah D. Angew Chem-Int Ed. 2005;44:4442–4489. - PubMed

    1. For general reviews of gold catalysis see: Shapiro ND, Toste FD. Synlett. 2010:675.Fürstner A. Chem Soc Rev. 2009;38:3208.Jiménez-Núñez E, Echavarren AM. Chem Rev. 2008;108:3326.Shen HC. Tetrahedron. 2008;64:7847.Gorin DJ, Sherry BD, Toste FD. Chem Rev. 2008;108:3351.Li Z, Brouwer C, He C. Chem Rev. 2008;108:3239.Arcadi A. Chem Rev. 2008;108:3266.Hashmi ASK. Chem Rev. 2007;107:3180.

    1. For early examples of this reactivity using cationic phosphinegold(I) complexes, see: Teles JH, Brode S, Chabanas M. Angew Chem, Int Ed. 1998;37:1415.Mizushima E, Sato E, Hayashi K, Tanaka TM. Angew Chem, Int Ed. 2002;41:4563.Reetz MT, Sommer K. Eur J Org Chem. 2003:3485.Mizushima E, Hayashi T, Tanaka M. Org Lett. 2003;5:3349.Nieto-Oberhuber C, Munuz MP, Bunuel E, Nevado C, Cardenas DJ, Echavarren AM. Angew Chem, Int Ed. 2004;43:2403.Kennedy-Smith JJ, Staben ST, Toste FD. J Am Chem Soc. 2004;126:4526.Mamane V, Gress T, Krause H, Fürstner A. J Am Chem Soc. 2004;126:8654.Luzung MR, Markham JP, Toste FD. J Am Chem Soc. 2004;126:10858.

    1. Hashmi SK, Ramamurthi TD, Rominger F. J Organomet Chem. 2009;694:592.
    1. Zhang GZ, Peng Y, Cui L, Zhang LM. Angew Chem-Int Ed. 2009;48:3112–3115. - PubMed
    2. Zhang GZ, Cui L, Wang YZ, Zhang LM. J Am Chem Soc. 2010;132:1474–1475. - PubMed
    3. Zhang G, Luo Y, Wang Y, Zhang L. Angew Chem Int Ed. 2011;50:4450. - PubMed

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