The ability of the isolated solid, to act as catalyst and base for the reaction introduces a possibility for air-stable catalytic precursor. Further work is necessary to understand whether the copper is “coating” the Cs2CO3, or a more complex matrix is formed,
stabilising the Cu(I) from disproportionation to the Cu(II) complex 72. Kinetic experiments and reaction optimisation will provide insight into the nature of the precipitate, and the role of cesium in the formation of it.
Summary and Conclusions
A variety of deactivation and inhibition pathways in the copper-catalysed C-N bond formation have been assessed using 1H and 133Cs NMR, EPR and atomic absorption spectroscopies, powder and single crystal X-ray diffraction analysis, SEM and EDX. The formation of a number of Cu(II) complexes of the type CuL2 have been observed
from reactions with Cu(I) salts, however EPR spectroscopy under turnover conditions showed that Cu(II) initially formed in solution quickly disappears upon heating. Despite this, without the presence of substrates, the Cu(II) signal in EPR does not disappear and so the substrates may be necessary to stabilise the Cu(I) species.
Precipitation of copper during turnover has been observed under numerous conditions and through the use of EDX, it is confirmed that interactions between the Cu species and Cs salts used in catalysis removes copper from solution. Under turnover conditions, AAS showed that a large proportion of copper remains in solution, whilst only very little cesium is in solution at any point. This poor solubility of Cs-salts was explored with
133Cs NMR showing that at 90 °C, CsI has a much higher solubility than Cs
2CO3. This
has a negative impact on the reactivity in copper catalysis due to the inhibition effect which was seen when various halide salts were introduced to the reaction conditions. A combination of competitive halogen exchange and solubility may be the cause for this inhibition, although the use of crown ethers can improve reactivity.
It is possible that the interaction of the halide salts with the copper species can prevent formation of active catalyst, or encourage the formation of a Cu(II) complex such as the novel isolated Cu-I-Cs complex 72. The formation of this complex may provide insight into the effect of various cations in catalysis, where coordination of the cation could have stabilisation or promoting effects in the catalytic cycle. Although the complex was shown to be catalytically inactive, formation of a similar complex whilst preventing the oxidation to Cu(II) may be possible with further work.
The complex interactions between copper and base led to investigations of the homogeneity of the active catalyst. Hot filtration experiments showed that despite the precipitation of copper, active copper does remain in solution. Alternatively, experiments in pre-forming a Cu/Cs species showed that the precipitated copper may
also be a source of active catalyst. It is therefore likely that exchange between copper in and out of solution is occurring on a reaction timescale when using Cs2CO3.
References
1. S. Sung, D. Sale, D.C. Braddock, A. Armstrong, C. Brennan and R.P. Davies,
ACS Catal., 2016, 6, 3965-3974.
2. C. Sambiagio, R.H. Munday, S.P. Marsden, A.J. Blacker and P.C. McGowan,
Chem. Eur. J., 2014, 20, 17606-17615.
3. C. He, G.H. Zhang, J. Ke, H. Zhang, J.T. Miller, A.J. Kropf and A.W. Lei, J. Am. Chem. Soc., 2013, 135, 488-493.
4. H. Weingarten, J. Org. Chem., 1964, 29, 3624-3626.
5. R. Cano, A.F. Schmidt and G.P. McGlacken, Chem. Sci., 2015, 6, 5338-5346. 6. D.A. Conlon, B. Pipik, S. Ferdinand, C.R. LeBlond, J.R. Sowa, B. Izzo, P.
Collins, G.J. Ho, J.M. Williams, Y.J. Shi and Y.K. Sun, Adv. Synth. Catal., 2003, 345, 931-935.
7. P.J. Ellis, I.J.S. Fairlamb, S.F.J. Hackett, K. Wilson and A.F. Lee, Angew. Chem. Int. Ed., 2010, 49, 1820-1824.
8. A.J. Reay and I.J.S. Fairlamb, Chem. Commun., 2015, 51, 16289-16307.
9. I.J.S. Fairlamb and A.F. Lee, 'Fundamental Pd-0/Pd-II Redox Steps in Cross- coupling Reactions: Homogeneous, Hybrid Homogeneous-Heterogeneous to Heterogeneous Mechanistic Pathways for C-C Couplings' Royal Society of Chemistry, United Kingdom, 2013, vol. 11.
10. R.H. Crabtree, Chem. Rev., 2012, 112, 1536-1554.
11. M. Parisien, D. Valette and K. Fagnou, J. Org. Chem., 2005, 70, 7578-7584. 12. D.S. Marlin, M.M. Olmstead and P.K. Mascharak, Inorg. Chem., 2001, 40, 7003-
7008.
13. A.W. Addison, T.N. Rao, J. Reedijk, J. Vanrijn and G.C. Verschoor, J. Chem. Soc., Dalton Trans., 1984, 1349-1356.
14. M. Kondo and M. Kubo, J. Phys. Chem., 1958, 62, 468-469. 15. J.D. Satterlee, Concepts Magn. Reson., 1990, 2, 119-129.
16. G. Dijkstra, W.H. Kruizinga and R.M. Kellogg, J. Org. Chem., 1987, 52, 4230- 4234.
17. L.L. Soong, G.E. Leroi and A.I. Popov, Inorg. Chem., 1990, 29, 1366-1370. 18. W.J. Dewitte, R.C. Schoening and A.I. Popov, Inorg. Nucl. Chem. Lett., 1976,
12, 251-253.
20. R.G.R. Bacon and H.A.O. Hill, J. Chem. Soc., 1964, 1108-&.
21. N.P. Rath and E.M. Holt, J. Chem. Soc., Chem. Commun., 1985, 665-667. 22. A.G. Orpen, L. Brammer, F.H. Allen, O. Kennard, D.G. Watson and R. Taylor,
J. Chem. Soc., Dalton Trans., 1989, S1-S83.
23. I.M. Muller and W.S. Sheldrick, Z. Anorg. Allg. Chem., 1999, 625, 443-448. 24. M. Heller and W.S. Sheldrick, Z. Anorg. Allg. Chem., 2003, 629, 1589-1595. 25. S. Jammi, S. Sakthivel, L. Rout, T. Mukherjee, S. Mandal, R. Mitra, P. Saha and
T. Punniyamurthy, J. Org. Chem., 2009, 74, 1971-1976.
26. J. Mondal, A. Biswas, S. Chiba and Y.L. Zhao, Sci. Rep., 2015, 5.
27. L. Rout, T.K. Sen and T. Punniyamurthy, Angew. Chem. Int. Ed., 2007, 46, 5583- 5586.
28. Y. Isomura, T. Narushima, H. Kawasaki, T. Yonezawa and Y. Obora, Chem. Commun., 2012, 48, 3784-3786.
5.