was negligible, as in the case without applied
bias, but under negative bias, the pre-edge feature became prominent. Because no electrochemical reactions or ion adsorption take place at
these bias voltages (fig. S2) (20), a simple interpretation of the observations is that under negative bias, the electric field favors an orientation of
the water molecules with their H atoms toward
the gold surface, which increases the number
of dangling hydrogen bonds. This hypothesis
was confirmed by our AIMD simulations, which
show an enhanced DD population at positive
bias and an enhanced SD population at negative
bias (Fig. 4). Indeed, at negative bias, the change
in the orientation of the water molecules greatly disrupts the hydrogen bonding network in the
interfacial layer (fig. S4) (20). This gives rise to
an increased SD|| population that causes a prominent pre-edge feature in the XAS.
Because XAS is element-specific, our experimental method opens the way for further studies
of the structure and chemistry of solvent and
solute species in the interfacial layers close to an
electrode (~1 nm), and in the presence of electric
fields. The complexity of the interfacial molecular rearrangements underscores the need for
accurate and efficient first-principles calculations to aid interpretation and, as in the present
case, to uncover previously unknown physics
related to the strong coupling of x-ray excited
states to surface electronic structure. This combined experimental and theoretical approach
is essential for a fundamental understanding
of electrochemical reactions, with applications
to electrocatalysis, photochemistry, and energy
storage, among others.
REFERENCES AND NOTES
1. A. J. Bard, L. R. Faulkner, Electrochemical Methods:
Fundamentals and Applications (Wiley, New York, 1980).
2. G. Cicero, J. C. Grossman, E. Schwegler, F. Gygi, G. Galli,
J. Am. Chem. Soc. 130, 1871–1878 (2008).
3. D. Chandler, Nature 437, 640–647 (2005).
4. P. Fenter et al., J. Colloid Interface Sci. 225, 154–165 (2000).
5. K. Ataka, T. Yotsuyanagi, M. Osawa, J. Phys. Chem. 100,
6. M. Fleischmann, P. J. Hendra, I. R. Hill, M. E. Pemble,
J. Electroanal. Chem. 117, 243–255 (1981).
7. Y. R. Shen, V. Ostroverkhov, Chem. Rev. 106, 1140–1154 (2006).
8. L. Zhang, C. Tian, G. A. Waychunas, Y. R. Shen, J. Am. Chem.
Soc. 130, 7686–7694 (2008).
9. V. Ostroverkhov, G. A. Waychunas, Y. R. Shen, Phys. Rev. Lett.
94, 046102 (2005).
10. J. Sung, L. Zhang, C. Tian, Y. R. Shen, G. A. Waychunas,
J. Phys. Chem. C 115, 13887–13893 (2011).
11. A. Nilsson et al., J. Electron Spectrosc. Relat. Phenom. 177,
12. H. Bluhm, D. F. Ogletree, C. S. Fadley, Z. Hussain, M. Salmeron,
J. Phys. Condens. Matter 14, L227–L233 (2002).
13. A. Nilsson, L. G. M. Pettersson, Surf. Sci. Rep. 55, 49–167
14. J.-H. Guo et al., Phys. Rev. Lett. 89, 137402 (2002).
15. O. Fuchs et al., Nucl. Instruments Methods A 585, 172–177 (2008).
16. T. Tokushima et al., J. Chem. Phys. 136, 044517 (2012).
17. J.-H. Guo et al., Phys. Rev. Lett. 91, 157401 (2003).
18. P. Jiang et al., Electrochem. Commun. 12, 820–822 (2010).
19. A. Braun et al., J. Phys. Chem. C 116, 16870–16875 (2012).
20. See supplementary materials in Science Online.
21. S. Ghosal et al., Science 307, 563–566 (2005).
22. M. A. Brown, M. Faubel, B. Winter, Annu. Rep. Prog. Chem.
Sect. C 105, 174 (2009).
23. D. Prendergast, G. Galli, Phys. Rev. Lett. 96, 215502 (2006).
24. U. Bergmann et al., Phys. Rev. B 66, 092107 (2002).
25. A. H. England et al., Chem. Phys. Lett. 514, 187–195 (2011).
26. W. S. Drisdell et al., J. Am. Chem. Soc. 135, 18183–18190 (2013).
27. P. Wernet et al., Science 304, 995–999 (2004).
28. G. Cicero, A. Calzolari, S. Corni, A. Catellani, J. Phys. Chem.
Lett. 2, 2582–2586 (2011).
29. R. Nadler, J. F. Sanz, J. Chem. Phys. 137, 114709 (2012).
30. D. Stacchiola et al., J. Phys. Chem. C 113, 15102–15105 (2009).
31. P. J. Feibelman, Science 295, 99–102 (2002).
32. A. Michaelides, A. Alavi, D. A. King, J. Am. Chem. Soc. 125,
33. M. Tatarkhanov et al., J. Am. Chem. Soc. 131, 18425–18434
34. G. Liu, M. Salmeron, Langmuir 10, 367–370 (1994).
35. M. F. Toney et al., Nature 368, 444–446 (1994).
This work was supported by the Office of Basic Energy Sciences
(BES), Division of Materials Sciences and Engineering, of the
U.S. Department of Energy (DOE) under contract no. DE-AC02-
05CH11231 (through the Chemical and Mechanical Properties
of Surfaces, Interfaces and Nanostructures program). J.-J.V.-V.
acknowledges financial support from the Alexander von Humboldt
Foundation, Germany. C.H. W. acknowledges the Advanced Light
Source (ALS) Doctoral Fellowship in Residence. Theory and
simulations by T.A.P., L.F. W., and D.P. were supported by the Joint
Center for Energy Storage Research, an Energy Innovation Hub
funded by the U.S. DOE and facilitated by a user project at the
Molecular Foundry. Computations were performed with the
computing resources of the National Energy Research Scientific
Computing Center (NERSC). The ALS and Molecular Foundry
(supported by DOE-BES) and NERSC (supported by
DOE–Advanced Scientific Computing Research) are DOE Office
of Science User Facilities, supported by the DOE Office of Science
under contract no. DE- AC02-05CH11231. We thank C.-H. Chuang,
B.-Y. Wang, D. Zhang, X. Feng, and M. W. West for support at
the beamline. We also thank J. Zhang for help with AFM imaging
and C. Das Pemmaraju, C. Schwartz, P. Ross, J. Colchero,
G. Thornton, H. Fang, and S. Harris for useful discussions.
Figs. S1 to S6
31 July 2014; accepted 9 October 2014
Published online 23 October 2014;
Directed ortho-meta′- and
meta-meta′-dimetalations: A template
base approach to deprotonation
Antonio J. Martínez-Martínez, Alan R. Kennedy, Robert E. Mulvey,* Charles T. O’Hara*
The regioselectivity of deprotonation reactions between arene substrates and basic
metalating agents is usually governed by the electronic and/or coordinative characteristics
of a directing group attached to the benzene ring. Generally, the reaction takes place in the
ortho position, adjacent to the substituent. Here, we introduce a protocol by which the
metalating agent, a disodium-monomagnesium alkyl-amide, forms a template that extends
regioselectivity to more distant arene sites. Depending on the nature of the directing
group, ortho-meta′ or meta-meta′ dimetalation is observed, in the latter case breaking the
dogma of ortho metalation. This concept is elaborated through the characterization of both
organometallic intermediates and electrophilically quenched products.
One of the most widely applied chemical reactions is metalation (1, 2), in which an inert carbon-hydrogen (C-H) bond is trans- formed to a more reactive carbon-metal (C-M) bond by a metalating agent. The
fundamental importance and vast scope of meta-
lation arise from the ubiquity of the C-H bond,
which is one of the most abundant bonds found
in nature and provides a rich sustainable entry
point for the synthesis of aromatic chemicals,
natural products, and organic-based materials.
However, this abundance of C-H bonds poses a
formidable challenge to synthetic chemists: How
can metalation reactions be made regioselective—
that is, to deprotonate specific C-H bonds with-
out reacting with other C-H bonds in the same
molecule? One answer arrived in “directed ortho-
metalation” (DoM) (3–6), the seminal concept to
date in metalation chemistry. First introduced
independently by Gilman (7) and Wittig (8), and
then greatly extended by Beak (9), Mortier (10),
Hoppe (11, 12), and Snieckus (13, 14), among
others, DoM relies primarily on the substitution
within the aromatic substrate undergoing the
C-H to C-M transformation. To induce the DoM
reaction, this substrate must contain a directing
metalation group (DG) that can activate an ad-
jacent (ortho) C-H bond toward metalation ei-
ther by providing the incoming Lewis acidic
metalating agent with a Lewis basic docking site
(coordination effect) and/or weakening this bond
through electron-withdrawing inductive proper-
ties (electronic effect) (Fig. 1). Depending on their
relative coordinating and electron-withdrawing
ability, DGs can be weak, moderate, or strong
In general, the DoM concept applies irrespective of which metalating agent is used, whether
it be an organolithium reagent or one of the
new wave of bimetallic formulations [typified
834 14 NOVEMBER 2014 • VOL 346 ISSUE 6211 sciencemag.org SCIENCE
WestCHEM, Department of Pure and Applied Chemistry,
University of Strathclyde, Glasgow G1 1XL, UK.
*Corresponding author. E-mail: firstname.lastname@example.org
(R.E.M.); email@example.com (C. T.O)