a strategy to take into account in the design of more efficient
III
Cu -mediated C–heteroatom bond-forming reactions.
We thank S. S. Stahl and L. M. Huffman for fruitful discussions.
We also thank T. Parella for help on the NMR analysis. We
acknowledge financial support from the MICINN of Spain
(CTQ2009-08464/BQU to M.C. and CTQ2008-03077/BQU to
M.S.), the DIUE of Catalonia (2009SGR637). A.C. thanks
MICINN for a PhD grant. M.C. and X.R. thank Generalitat de
Catalunya for ICREA Academia Awards and 2009 SGR637. We
also thank STR-UdG for NMR and ESI-MS technical support.
Notes and references
III
Fig. 5 Proposed mechanism for the reactivity of aryl–Cu species 2 with
pX-phenolates (sodium salt).
1 I. Goldberg, Ber. Dtsch. Chem. Ges., 1906, 39, 1691–1696.
2 F. Ullmann, Ber. Dtsch. Chem. Ges., 1903, 36, 2389.
3 F. Ullmann and J. Bielecki, Chem. Ber., 1901, 34, 2174.
4 E. Sperotto, G. P. M. v. Klink, G. v. Koten and J. G. d. Vries, Dalton
Trans., 2010, 39, 10338–10351.
Given the above reported data, we can tentatively propose the
mechanism depicted in Fig. 5 for the equimolar reaction of 2
with pX-PhONa. The first step consists of the deprotonation of
one secondary amine by the basic phenolate to yield 3 and the
corresponding phenol. At this point, deprotonated Cu complex
3 interacts with in situ formed phenol substrate and undergoes
5 I. P. Beletskaya and A. V. Cheprakov, Coord. Chem. Rev., 2004, 248,
2337–2364.
III
6 G. Evano, N. Blanchard and M. Toumi, Chem. Rev., 2008, 108, 3054–
3131.
7 F. Monnier and M. Taillefer, Angew. Chem., Int. Ed., 2009, 48, 6954–
6971.
I
reductive elimination to form the final aryl–O and Cu products.
This reaction is much faster than that of complex 2 with phenols.
The proposal of a reductive elimination step is consistent with
several examples in the literature of reactions between well-defined
8 L. M. Huffman, A. Casitas, M. Font, M. Canta, M. Costas, X. Ribas
and S. S. Stahl, Chem. Eur. J., 2011, DOI: 10.1002/ chem.201100608.
9 X. Ribas, C. Calle, A. Poater, A. Casitas, L. Go´mez, R. Xifra, T. Parella,
J. Benet-Buchholz, A. Schweiger, G. Mitrikas, M. Sola`, A. Llobet and
T. D. P. Stack, J. Am. Chem. Soc., 2010, 132, 12299–12306.
10 X. Ribas, D. A. Jackson, B. Donnadieu, J. Mah´ıa, T. Parella, R. Xifra,
B. Hedman, K. O. Hodgson, A. Llobet and T. D. P. Stack, Angew.
Chem., Int. Ed., 2002, 41, 2991–2994.
11 M. Albrecht and G. van Koten, Angew. Chem., Int. Ed., 2001, 40,
3750–3781.
12 R. H. Crabtree, Science, 2010, 330, 455–456.
13 T. A. Neubecker, S. T. Kirksey, K. L. Chellappa and D. W. Margerum,
Inorg. Chem., 1979, 18, 444–448.
III
aryl–Cu species and N- and O-nucleophiles,8,20,21 as well as with
aryl-halide reductive elimination examples at well-defined aryl–
III
III
Cu -halides.22 Furthermore, reductive elimination at aryl–Cu
species is also proposed in mechanistic studies on Ullmann-like
coupling reactions.4,7,23,24
In addition, in a side reaction (2–11%), 3 can undergo 1e-
II
reduction to form an aryl–Cu N3 species 3¢ with a tetrahedral
coordination geometry. The origin of the e- could not be ascer-
14 S. T. Kirksey and D. W. Margerum, Inorg. Chem., 1979, 18, 966–970.
15 The same violet species 3 is obtained by reaction of 2 with sodium
I
tained, but possible sources could be Cu , PhOH and PhO- species,
III
acetate, no deprotonation is achieved by treating aryl–Cu -halide
all of them present in the reaction mixture. Whatever its origin,
since aryl–ONuc products are obtained in quantitative yield, we
conclude that 3¢ is also consumed in the reaction, and that side
reactivity of 3 to form 3¢ must be reversible.
species with base due to the enhanced stability (see ref. 8); furthermore,
the addition of one equiv. of Cl- to 3 forms quenches inmediately its
III
violet color and forms aryl–Cu -Cl (see ref. 22).
16 C. P. Keijzers, G. F. M. Paulussen and E. D. Boer, Mol. Phys., 1975,
29, 973–1006.
Summarizing, we have demonstrated that the reactivity of well-
17 J. E. Roberts, T. G. Brown, B. M. Hoffman and J. Peisach, J. Am. Chem.
Soc., 1980, 102, 825–829.
III
defined aryl–Cu species in front of phenol-type nucleophiles
differs substantially from the reactivity with corresponding phe-
nolates, and a significant enhancement is found to produce the
same aryl–O coupling product. Mechanistic studies show that easy
deprotonation of coordinated secondary amines is responsible of
the intense LMCT band at 545 nm; indeed, this pH-dependent
reactivity of the pincer-like coordinated ligand somewhat enhances
its reactivity. The origin of such enhancement is not clearly
understood, and is currently been studied computationally. A
parallel reaction path for deprotonated species 3 affords minor
quantities of an EPR-active species 3¢. The present observations
of a substantial enhancement in the cross-coupling reactivity
observed upon ligand deprotonation suggests that this might be
18 A. Romero, C. W. Hoitink, H. Nar, R. Huber, A. Messerschmidt and
G. W. Canters, J. Mol. Biol., 1993, 229, 1007–1021.
19 S. D. George, L. Basumallick, R. K. Szilagyi, D. W. Randall, M. G.
Hill, A. M. Nersissian, J. S. Valentine, B. Hedman, K. O. Hodgson and
E. I. Solomon, J. Am. Chem. Soc., 2003, 125, 11314–11328.
20 L. M. Huffman and S. S. Stahl, J. Am. Chem. Soc., 2008, 130, 9196–
9197.
21 A. E. King, L. M. Huffman, A. Casitas, M. Costas, X. Ribas and S. S.
Stahl, J. Am. Chem. Soc., 2010, 132, 12068–12073.
22 A. Casitas, A. E. King, T. Parella, M. Costas, S. S. Stahl and X. Ribas,
Chem. Sci., 2010, 1, 326–330.
23 H.-Z. Yu, Y.-Y. Jiang, Y. Fu and L. Liu, J. Am. Chem. Soc., 2010, 132,
18078–18091.
24 G. O. Jones, P. Liu, K. N. Houk and S. L. Buchwald, J. Am. Chem.
Soc., 2010, 132, 6205–6213.
This journal is
The Royal Society of Chemistry 2011
Dalton Trans., 2011, 40, 8796–8799 | 8799
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