Preferential cross-coupling of naphthol derivatives mediated by copper(II)

Article abstract of DOI:10.1002/poc.3086

Preferential cross-coupling of differently N-substituted amides of 3-hydroxy-2-naphthoic acids 1 and 2 catalyzed by Cu(OH)Cl?TMEDA was observed. The reaction mechanism was investigated using mass spectrometry tools. It was shown that the complexation properties of the N-substituent significantly influence the properties of the corresponding copper complexes of the deprotonated compounds ([(1-H)Cu(TMEDA)]⁺ and [(2-H)Cu(TMEDA)]⁺). Analysis of the fragmentation patterns of the copper complexes revealed that while the former is prone to the one electron oxidation of (1-H)^-, the latter has a larger binding energy between (2-H)^- and copper(II). Interplay between the abundance of the copper complexes and their reactivities explains the preferential cross-coupling. The results are further supported by exploratory density functional theory calculations. Copyright

Full text of DOI:10.1002/poc.3086

Special Issue Article
Received: 31 October 2012,
Revised: 21 December 2012,
Accepted: 27 December 2012,
Published online in Wiley Online Library: 2013
(wileyonlinelibrary.com) DOI: 10.1002/poc.3086
Preferential cross-coupling of naphthol
derivatives mediated by copper(II)†
a
b
c
ꢀ
ꢀ
ꢀ
Simona Koscová , Jana Roithová * and Jana Hodacová
Preferential cross-coupling of differently N-substituted amides of 3-hydroxy-2-naphthoic acids 1 and 2 catalyzed by
Cu(OH)Cl•TMEDA was observed. The reaction mechanism was investigated using mass spectrometry tools. It was
shown that the complexation properties of the N-substituent significantly influence the properties of the
corresponding copper complexes of the deprotonated compounds ([(1-H)Cu(TMEDA)]+ and [(2-H)Cu(TMEDA)]+).
Analysis of the fragmentation patterns of the copper complexes revealed that while the former is prone to the one
electron oxidation of (1-H)ˉ, the latter has a larger binding energy between (2-H)ˉ and copper(II). Interplay between
the abundance of the copper complexes and their reactivities explains the preferential cross-coupling. The results
are further supported by exploratory density functional theory calculations. Copyright © 2013 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this paper
Keywords: BINOL; copper; cross-coupling; DFT calculations; mass spectrometry; reaction mechanisms
Some remarkably selective cross-coupling reactions have been
INTRODUCTION
observed for the copper(II)-mediated reactions.[30] For example, a
mixture of 2-naphthol and 2-naphthylamine leads preferentially
to the cross-coupled product.[20] The available explanation for
the observed reactivity is based on the electronic structure of
the isolated reactants. It has been suggested that the reactivity
is driven by the feasibility of the creating the corresponding
naphthoxy radicals and by the relative energies of the highest
occupied- and the lowest unoccupied molecular orbital of these
radicals.[26] This simple scheme can explain the reactivity in the
naphthol cross-coupling to a certain degree and correlates well
with some observed selectivities; however, the coordinated
copper ion will influence all these properties in that it primarily
significantly changes the distribution of the spin density[31] and
also the geometry of the naphthoxy radical can be drastically
changed. Thus, in the light of the recent mechanistic proposals,
Biaryl compounds, in particular 2,2’-disubstituted 1,1’-binaphthyls,
play an important role as ligands in the metal-catalyzed enantiose-
lective synthesis.[1–3] The classical representative of these axially
chiral ligands is BINOL (2,2’-dihydroxy-1,1’-binaphthyl).[4] The strat-
egy for the preparation of BINOL and its derivatives often involves
oxidative coupling of two naphthol units in the presence of various
oxidants based on transition metals ranging from titanium[5] and
vanadium[6–12] via iron[13] and manganese[14] to copper[15] com-
plexes. The traditional preparations of BINOL and its derivatives[16]
require stoichiometric amounts of oxidants, but also some catalytic
processes were developed, usually with oxygen serving as the
terminal oxidant.[17–19] Enantiomerically pure binols can be pre-
pared either by resolution of a racemic product[1], or chirality can
be induced already during the synthesis in order to directly pre-
pare enantiomerically pure product.[18,20–22] In addition, further
asymmetry in binol compounds can be introduced by cross-
coupling of different naphthol molecules, which leads to binols
with different subunits.[23–26]
* Correspondence to: J. Roithová, Department of Organic Chemistry, Faculty of
Science, Charles University in Prague, Czech Republic.
E-mail: roithova@natur.cuni.cz
Several scenarios have been proposed as the mechanism for
the naphthol coupling. While it is broadly accepted that the
metal ion is present at the “reaction center” during the whole
course of the reaction, the consensus about the particular form
of the reaction complex has not been achieved. For the cou-
pling catalyzed by vanadium oxides, it is usually assumed that
a binuclear complex is formed, in which two naphthol mole-
cules are bound to two vanadium atoms.[11] On the other hand,
for the coupling catalyzed by copper(II), usually a mononuclear
complex of the copper ion and a naphtholate ligand is assumed
to react with another naphthol molecule from the solution.[27]
On contrary, we have recently shown that at least in the gas
phase, the copper-mediated naphthol coupling proceeds in
binuclear clusters (Scheme 1) analogous to those proposed
for vanadium-catalyzed reactions and that the mononuclear
clusters do not show any significant reactivity as carbon-
centered radicals.[28,29]
†
This article is published in Journal of Physical Organic Chemistry as a special
issue on ISRIUM 2012 by Igor Alabugin (Department of Chemistry and
Biochemistry, 102 Varsity Way, 5008 CSL, Florida State University, Tallahassee,
FL 32306-4390, USA), Chris Cramer (University of Minnesota, Department of
Chemistry, 207 Pleasant Street SE, Minneapolis, MN 55455-0431, USA) and
Rik Tykwinski (Friedrich-Alexander-Universität Erlangen-Nürnberg, Lehrstuhl
für Organische Chemie I, Henkestrabe 42, D-91054 Erlangen, Germany).
ꢀꢀ
a S. Koscová
Institute of Organic Chemistry and Biochemistry, Flemingovo nám. 2, 16610
Praha 6, Czech Republic
b J. Roithová
Department of Organic Chemistry, Charles University, Hlavova 8, 12840
Praha 2, Czech Republic
ꢀ
c J. Hodacová
Department of Organic Chemistry, Institute of Chemical Technology, Technická
5, 16628, Praha 6, Czech Republic
J. Phys. Org. Chem. 2013
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S. KOscOVÁ, J. ROITHOVÁ AND J. HODAcOVÁ
Scheme 1. Proposed mechanism for copper mediated naphthol coupling.
Scheme 2. The investigated reactants and products.
the present work aims in the investigation of the role of the
copper ion in the preferential cross-coupling by means of mass
spectrometry. Two different amides of 2-hydroxy-3-naphthoic acid
1 and 2 (Scheme 2) were chosen as precursor molecules, because
due to the same functionalities at the naphthalene rings, roughly
similar electronic properties can be expected, but completely
different binding abilities with respect to copper are foreseen.
73%, and 5%, respectively.[33] These results clearly show that
the cross-coupling between the amides 1 and 2 is favored to
the homo-coupling. In the following, we aim to answer these
questions: (i) Do properties of complexes of 1 and 2 with
copper and the nitrogen ligand substantially differ? (ii) Do reac-
tivities of binuclear clusters of copper with the amides 1 and 2
differ? (iii) Is there a special role of TMEDA? To answer these
questions, the complexes of naphthols 1 and 2 with CuII and
CuII•TMEDA are investigated by means of mass spectrometry,[34–38]
and the interpretation is supported by exploratory density
functional theory (DFT) calculations.
RESULTS AND DISCUSSION
The preparative cross-coupling of amides 1 and 2 mediated by
stoichiometric amount of Cu(OH)Cl•TMEDA [32] leads to a signif-
icantly enhanced yield of the mixed product 4 compared to the
homo-coupled products 3 and 5. According to the analysis of
the reaction by high pressure liquid chromatography, the ratio
of the products 3 : 4 : 5 amounts to 9% : 82% : 9%. The analo-
gous preparative reaction led to the isolated yields of 16%,
Complexes of 1
In order to discern the effect of the TMEDA ligand, methanolic
solutions of 1 with Cu(NO3)2 and Cu(OH)Cl•TMEDA, respectively,
are investigated by means of electrospray ionization (ESI) mass
spectrometry, and the formation of various complexes and their
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COPPER CATALYSIS
unimolecular behavior are compared. In the absence of TMEDA,
the relevant complexes generated upon ESI correspond to [(1-H)
Cu]+ (m/z 325), its methanol adduct [(1-H)Cu(CH3OH)]+ (m/z 357),
the analogous adduct with naphthol [(1-H)(1)Cu]+ ion (m/z 588),
and the binuclear copper complex [(1-H)2Cu2(NO3)] (m/z 712)
(Fig. S1a, supplementary material). The initial question concerns
the structure of the [(1-H)Cu]+ ion, because copper may bind
to the oxygen atom of the hydroxy group, but the possibilities
of binding to the amide nitrogen or the aromatic moiety should
be considered as well. Based on the analogy with the complex of
CuII with phenolate,[39–41] it can be expected that copper binds
rather to the deprotonated oxygen (or nitrogen) atom rather than
to the aromatic moiety. The collision-induced dissociation (CID) of
mass-selected [(1-H)Cu]+ reveals the formation of PhNHCu+
(Ph = phenyl) as the dominant reaction (Fig. 1a). Another fragmen-
for the occurrence of bond activations. In addition, also analo-
gous reactions of [(1-H)Cu(CH3OH)]+ and [(1-H)(1)Cu]+ were con-
ducted, and the exchange of closed-shell ligands by the neutral
reactant was observed as the exclusive reaction channel.
With regard to the coupling processes, the dissociation of the
binuclear complex [(1-H)2Cu2(NO3)]+ is important. It has been
proposed that in such complexes, the coupling reaction takes
place.[28] However, the CID of [(1-H)2Cu2(NO3)]+ shows the elim-
ination of HNO3 as the major channel, which has been confirmed
by control experiments with other isotopic ions of [(1-H)2Cu2
(NO3)]+ (Fig. S2a, supplementary material). This type of fragmen-
tation is observed also for the dissociation of the analogous
binuclear complex of methyl-3-hydroxy-2-naphthoate; however,
in that case, it represents only a minor channel. Thus, it seems that
hydrogen available from the amide group in 1 causes the
preference for the elimination of HNO3 with respect to the
coupling reaction. The second most abundant fragmentation of
[(1-H)2Cu2(NO3)]+ leads to a cluster cleavage to yield [(1-H)Cu]+
and [(1-H)Cu(NO3)], and finally also elimination of the radical
•
tation channel is represented by a loss of the PhNH radical. These
experimental results suggest that the naphthol compound 1 is
not deprotonated at the nitrogen atom; instead, it is deprotonated
at the oxygen site and copper accordingly binds to oxygen.
The CID experiments with [(1-H)Cu(CH3OH)]+ and [(1-H)(1)Cu]+
show, as expected, dominant losses of the closed-shell ligands CH3OH
and 1, respectively. In addition, the fragmentation of [(1-H)(1)Cu]+
•
(1-H) can be identified. Thus, it appears that the cross-coupling
reaction is too slow to occur in the time-window of the experiment.
ESI of the solution of 1 and Cu(OH)Cl•TMEDA in the mix-
ture methanol/CH2Cl2/H2O yields a variety of ions (Fig. S3,
supplementary material), among which a complex with the
composition [(1-H)Cu(TMEDA)]+ (m/z 441) is dominant. Rele-
vant complexes containing two copper ions and two units
of 1 are represented by [(1-H)2Cu2Cl(TMEDA)]+ (m/z 801)
and [(1-H)2Cu2Cl(TMEDA)2]+ (m/z 917). With increasing time
of the experiment also, signal corresponding formally to
{[(12-3H)Cu(TMEDA)]}+ (m/z 702) appears, which most proba-
bly represents the complex [(3-H)Cu(TMEDA)]+ of the binol
3 formed in the solution.
•
leads also to the elimination of the radical (1-H) as a byproduct in a
1 : 10 ratio with respect to the elimination of 1. This finding again
shows the ability of copper to accept one electron from the
II
I
•
naphthoxo ligand (1-H), thereby undergoing a reduction of Cu to Cu.
The localization of the unpaired electron at carbon atoms of
the naphthoxy unit of [(1-H)Cu]+ was tested in its reactions with
1,4-cyclohexadiene, methyl iodide, and dimethyldisulphide
(DMDS). It is expected that carbon centered radicals are able to
activate these molecules.[42] All these reactions led only to for-
mations of the corresponding adducts without apparent hints
Figure 1. CID spectra of (a) [(1-H)Cu]+, (b) [(1-H)Cu(TMEDA)]+, (c) [(2-H)Cu]+, and (d) [(2-H)Cu(TMEDA)]+. Collision energies in the center-of-mass frame
were 2.9 eV, 3.4 eV, 3.1 eV, and 2.7 eV, respectively; collision gas: xenon
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S. KOscOVÁ, J. ROITHOVÁ AND J. HODAcOVÁ
The CID experiment with mass-selected [(1-H)Cu(TMEDA)]+
reveals almost exclusive elimination of the (1-H) radical concomitant
The complexes [(1-H)2Cu2Cl(TMEDA)]+ and [(1-H)2Cu2Cl
(TMEDA)2]+ have been suggested as those, in which the coupling
reaction may proceed.[28,29] The main reactive pathways sug-
gested correspond to eliminations of the corresponding binol
and formations of CuI complexes [Cu2Cl(TMEDA)]+ and [Cu2Cl
(TMEDA)2]+, respectively (Scheme 1). The dominant fragmen-
tation of [(1-H)2Cu2Cl(TMEDA)]+ upon CID leads to the clus-
ter cleavage to form [(1-H)Cu(TMEDA)]+ and [(1-H)CuCl] (Fig. 2b,
Scheme 3). This result indicates that the parent ion contains two
independent (1-H)Cu+ units bound via a chlorine anion and pre-
sumably also the TMEDA ligand, but TMEDA can, of course, also
bind to one copper center only (only the bridged structure is
shown in Scheme 3). The second most abundant peak corre-
sponds to the loss of TMEDA (m/z 686). If the fragmentation would
•
with the formation of [Cu(TMEDA)]+ (Fig. 1b). Detailed inspection of
the CID spectrum reveals a trace elimination of TMEDA from the
parent complex to yield [(1-H)Cu]+ ion in a ratio about 1 : 20 with
respect to [Cu(TMEDA)]+. Further, also neutral naphthol 1 is elimi-
nated concomitant with the formation of [Cu(TMEDA-H)]+ (insert in
Fig. 1b). The degree of localization of the radical site at the carbon
atoms is again probed by the reaction with DMDS. The reaction leads
•
dominantly to an exchange of the (1-H) ligand to form [(DMDS)Cu
(TMEDA)]+; as a minor channel, also the adduct [(1-H)Cu(TMEDA)
(DMDS)]+ is observed. Similar to monocopper complexes without
TMEDA, however, no S–S bond activation of DMDS is detected.
As far as the relevant coupling products are concerned, the
complex with m/z 702, which most probably corresponds to
the composition [(3-H)Cu(TMEDA)]+, is investigated first. The
CID experiment shows a loss of the fragment with Δm/z = 134,
which corresponds to the combined loss of TMEDA and water,
as the dominant reaction (Fig. 2a). The so-formed ion (m/z 568)
can further expel aniline from the amide moiety, which leads
to the ion with m/z 475. Aniline can also be eliminated in the first
step of the fragmentation of the parent ion (formation of the ion
with m/z 609). In the lower mass region of the CID spectrum, the
formation of the complex [Cu(TMEDA)]+ is observed, which corre-
•
correspond to the uncoupled product, then a loss of (1-H) should
prevail over the loss of TMEDA. We do not observe any loss of (1-
•
H), and therefore the loss of TMEDA is considered as a sign of the
coupling reaction (Scheme 3). In addition, two almost negligible
peaks can be discerned m/z 587 and m/z 277. The first one corre-
sponds to loss of TMEDA and CuCl, which thus leads to a complex
between binol 3 and CuI. The second one, even less abundant,
corresponds to the formation of [Cu2Cl(TMEDA)]+ (m/z 277) and
concomitant elimination of the binol 3.
CID of the larger complex [(1-H)2Cu2Cl(TMEDA)2]+ also mainly
leads to fragments with only one copper atom, i.e. [(1-H)Cu
(TMEDA)]+ and [(1-H)CuCl(TMEDA)] (Fig. S4 in the Supporting
Information). Other channels involve the elimination of the
•
sponds to the loss of the radical (3-H). All together, the CID spec-
trum is consistent with the formation of the coupled product 3 in
the solution, whose deprotonated form is complexed to copper
(Fig. 2a). This suggestion was verified independently by measuring
the ESI spectrum of the binol 3 in the presence of Cu(OH)Cl•TMEDA.
Thus, the dominant peak in the spectrum corresponds to [(3-H)Cu
(TMEDA)]+ (m/z 702), and the CID spectrum of the mass-selected
[(3-H)Cu(TMEDA)]+ is identical with that of the corresponding ion
generated from the solution of naphthol 1 (Fig. 2a).
+
•
TMEDA ligand, (1-H) and the formation of [Cu2Cl(TMEDA)2]
(m/z 393), which most probably reflects the coupling reaction
leading to the product 3.
Finally, the results are complemented by the DFT calculations
of complexes containing one copper atom (Fig. 3). For the bare
complex [(1-H)Cu]+, the most stable structure located indeed
corresponds to the isomer with copper bound to both oxygen
atoms. The alternative isomer with copper bound to the oxygen
atom and the nitrogen atom lies 0.67 eV (65 kJ molÀ1) higher in
energy. This finding is thus consistent with the interpretation
based on the experimental results. Further, we have shown pre-
viously that the coordination of copper(II) to phenolate leads to a
transfer of an electron and formation of a complex between cop-
per(I) and the phenoxy radical.[31,39] In agreement, all structures
located for the [(1-H)Cu]+ complex have a negligible localization
of an unpaired electron at copper, and the radical site is localized
at the naphthoxy unit.
For further evaluation of the reactivity, the most important re-
sult arises from the comparison of the fragmentations of [(1-H)
Cu(TMEDA)]+ and [(3-H)Cu(TMEDA)]+. While the fragmentation of
[(1-H)Cu(TMEDA)]+ leads dominantly to the elimination of (1-H),
•
the coupled product 3 binds much more strongly to the copper
center, and the eliminations associated with loss of TMEDA prevail.
In order to facilitate the computations, we have replaced the
TMEDA ligand by ethylene diamine (en) in the theoretical stud-
ies. The coordination of the bidentate base to the copper atom
of [(1-H)Cu]+ is associated with 3.23 eV (312 kJ molÀ1) binding
energy and leads to a complete change of the electronic struc-
ture of the complex. The unpaired electron is localized mostly
at copper, whereas the spin density at the aromatic moiety is
only negligible. This phenomenon has been shown already
earlier for the complex of the phenoxy ligand and copper
([(PhO)CuLn]+). The number n of additional ligands L crucially
influences the electronic structure of the complex.[40] If copper
bears only one additional monodentate ligand, then the complex
contains copper(I) and the phenoxy radical. Coordination of more
ligands, i.e. ligand field effect, leads to the stabilization of copper
(II). Here, copper is coordinated formally from two sides already
in the bare complex [(1-H)Cu]+, and therefore any additional
ligand (or a solvent molecule) will induce the electronic change
and diminishment of the radical site at the aromatic ring.[40] This
Figure 2. CID spectrum of (a) [(3-H)Cu(TMEDA)]+ at Ecoll = 3.2 eV and (b)
of [(1-H)2Cu2Cl(TMEDA)]+ at Ecoll = 1.4 eV generated by ESI of a CH3OH/
CH2Cl2/H2O solution of 1 and Cu(OH)Cl•TMEDA. Collision energies given
in the center-of-mass frame; collision gas: xenon
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COPPER CATALYSIS
Scheme 3. Fragmentation pathways of [(1-H)2Cu2Cl(TMEDA)]+ and [(1-H)2Cu2Cl(TMEDA)2]+. Note that TMEDA can act as a chelating or bridging ligand;
only one variant is shown here, but we do not intend to exclude the other possibility
Figure 3. B3LYP/SDD optimized structures of [(1-H)Cu]+ (E0K = À1057.028983 hartree), its isomer lying 0.67 eV (65 kJ molÀ1) higher in energy, and the
[(1-H)Cu(en)]+ complex (E0K = À1247.527204 hartree)
explains why the complexes of a naphtholate, copper(II), and an
additional ligand do not react as carbon-centered radicals.
ligands is high as evidenced by the rather high binding energy
with ethylenediamine.
As mentioned above, the bare complex [(1-H)Cu]+ also does
not show any reactivity as a carbon-centered radical although
the theoretical results show that there is a significant carbon-
radical character. It can be simply explained by a facile asso-
ciation of the other reactant (e.g. DMDS) to copper, which
induces electronic changes and diminishes the spin density
at the aromatic moiety. It has to be noted that copper(I) is ide-
ally coordinated by two ligands in the linear arrangement,
which cannot be achieved in [(1-H)Cu]+ simply due to the
geometry of 1. The copper center is therefore in energetically
disfavored geometry, and consequently the affinity for additional
Complexes of 2
ESI of the naphthol 2 and Cu(NO3)2 dissolved in a mixture of meth-
anol and water yields [(2-H)Cu]+ (m/z 495) as the dominant ion
(Fig. S1b, supplementary material). Other relevant ions corre-
spond to the protonated naphthol 2H+, the complex [(2-H)(2)Cu]+
(m/z 928), and finally the binuclear copper complex [(2-H)2Cu2NO3]+
(m/z 1052). The CID of the major ion [(2-H)Cu]+ shows fragmenta-
tion of the crown substituent, in which subsequent losses of C2H4
and CH2O units can be traced out (Fig. 1c). CID of the bisligated ion
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S. KOscOVÁ, J. ROITHOVÁ AND J. HODAcOVÁ
[(2-H)(2)Cu]+ shows exclusive elimination of the neutral naphthol 2
The computational results provide a clear rationale for the
observed dramatic differences between the complexation prop-
erties of (1-H)ˉ and (2-H)ˉ toward copper(II). In the most stable
geometry found for the [(2-H)Cu]+ complex, the crown substitu-
ent participates in the complexation of copper (Fig. 5) and pro-
vides thus a ligand field which stabilizes the whole complex.
Due to the coordination from four sides, the copper center stays
in the oxidation state II (spin localization on copper amounts to
0.646). For comparison, the most stable isomer, in which the
crown substituent does not participate in the complexation of
copper, lies 1.74 eV (168 kJ molÀ1) higher in energy. As expected
for the copper ion being bound only to two oxygen atoms, it is in
the reduced + I oxidation state, and the radical site is located at
the naphthoxy unit.
and in contrast to the fragmentation of the analogous complex of
•
1, no expulsion of the radical (2-H) is observed. The reactions of
mass-selected [(2-H)Cu]+ with CH3I and CH3SSCH3, respectively,
lead to only negligible amount of adduct formation without any
evidence for the presence of a carbon-centered radical.
The fragmentation of the binuclear copper complex
[(2-H)2Cu2NO3]+ preferentially leads to the cluster cleav-
age yielding [(2-H)Cu]+ concomitant with neutral [(2-H)CuNO3]
(Fig. S2b, supplementary material). Elimination of HNO3
constitutes a negligible channel, which supports the rationale
that the dominance of this channel in the fragmentation of
[(1-H)2Cu2NO3]+ is caused by the hydrogen atom of the amide
group of 1. Finally, again, no indications for the occurrence of
the coupling reaction are obtained.
The presence of TMEDA in the mixture leads to an ESI spectrum
with TMEDA adducts of [(2-H)Cu]+, [(2-H)Cu(TMEDA)]+ (m/z 611),
and binuclear complex [(2-H)2Cu2Cl(TMEDA)]+ (m/z 1141) as the
dominant signals (Fig. S3b). In addition, also signals corresponding
to [(22-3H)Cu(TMEDA)]+ (m/z 1042) and [(2-H)2Cu2Cl(TMEDA)2]+
(m/z 1257) are observed. At the first sight, the fragmentation of
the TMEDA complex [(2-H)Cu(TMEDA)]+ (Fig. 1d) is fundamentally
different from that of the analogous ion [(1-H)Cu(TMEDA)]+
(Fig. 1b). Elimination of TMEDA is observed as the almost exclusive
fragmentation, and only traces of [(TMEDA)Cu]+ can be identified
at m/z 179. This finding implies that (2-H) is much more strongly
bound to copper than (1-H). It can be explained by a participation
of the crown substituent in the bonding of the ligand to copper.
In the reactions of [(2-H)Cu(TMEDA)]+ with CH3I and CH3SSCH3,
respectively, not only no bond activation is observed, but the
complex even does not form any adducts on contrary to the other
studied ions (see above).
Several isomers of [(2-H)Cu(en)]+ have been found very close
in energy. Most interestingly, the additional coordination of cop-
per by the crown substituent does not bring substantial stabiliza-
tion and is even disfavored entropically (the crown-coordinated
isomer is in comparison to the other isomer depicted in Fig. 5
by 0.04 eV (4 kJ molÀ1) more stable at 0 K, but 0.11 eV
(11 kJmolÀ1) less stable at 298 K considering the Gibbs energies).
If we consider the high-energy lying isomer of [(2-H)Cu]+ (the
crown substituent does not coordinate to copper), the binding
energy to ethylenediamine amounts to 2.93eV (283 kJ molÀ1).
Thus, it is slightly smaller than that found for the binding between
ethylenediamine and [(1-H)Cu]+, but in the same energy range.
However, if we include the participation of the crown substituent,
then the binding energy drops to only 1.19eV (115kJmolÀ1). Thus,
the ability of the crown substituent to coordinate to copper
decreases the binding energy of the copper complex to the
diamine by about two thirds.
The fragmentation of [(22-3H)Cu(TMEDA)]+ exclusively leads to
the elimination of TMEDA. In analogy to [(12-3H)Cu(TMEDA)]+,
the (22-3H) unit most probably corresponds to the deproto-
nated coupling product 5. Fragmentation of the bicopper com-
plex [(2-H)2Cu2Cl(TMEDA)]+ leads to a dominant cluster cleavage
to form neutral [(2-H)CuCl(TMEDA)] and [(2-H)Cu(TMEDA)]+,
respectively; the latter ion can subsequently further lose TMEDA
(Fig. 4). Other channel leads to the elimination of TMEDA, which
however here cannot be ascribed to the coupling reaction,
because the uncoupled product also preferentially eliminates the
TMEDA ligand. The only channel indicating the coupling reaction
thus remains formation of [(2-H)2Cu]+ (i.e. [(5)Cu]+), which contains
reduced copper(I). The putative dicopper cluster [(2-H)2Cu2Cl
(TMEDA)2]+ was not produced in an amount sufficient for studying
the mass-selected ions.
Mixed complexes of 1 and 2
In order to address the questions posed at the outset, mixed
complexes of naphthols 1 and 2 generated from their solution
with Cu(OH)Cl•TMEDA in methanol/CH2Cl2/H2O were investi-
gated. The relevant mixed complexes obtained correspond to
[(1-H)(2-2H)Cu(TMEDA)]+ (m/z 872), [(1-H)(2-H)Cu2Cl(TMEDA)]+
(m/z 971), and [(1-H)(2-H)Cu2Cl(TMEDA)2]+ (m/z 1087). The CID
spectrum of {[(1-H)(2-2H)Cu(TMEDA)]}+ reveals a profound loss
of the TMEDA ligand, but also a small channel leads to the forma-
tion of [Cu(TMEDA)]+. The fragmentation is identical with that of
the binol complex [(4-H)Cu(TMEDA)]+ suggesting again that the
coupling reaction takes place in the solution. The spectrum
suggests that binol 4 is deprotonated at the unit corresponding
to naphthol 2, and only a small part of ions is deprotonated
at the naphthol unit 1 as indicated by a small abundance of
[Cu(TMEDA)]+ in the CID spectrum.
The major dissociation of the complex [(1-H)(2-H)Cu2Cl
(TMEDA)]+ corresponds to the formation of [(1-H)CuCl] and
[(2-H)Cu(TMEDA)]+ (Fig. 6). The second abundant fragmentation
•
leads to the elimination of the (1-H) radical from the parent
ion. With lower abundances then follow dissociations into
[(1-H)Cu(TMEDA)]+ and [(2-H)CuCl], [(1-H)CuCl(TMEDA)], and
[(2-H)Cu]+. This fragmentation pattern demonstrates once more
the larger ability of naphthol 2 to bind to copper compared to
naphthol 1. Further, the eliminations of the TMEDA ligand and
CuCl(TMEDA) are observed, where the latter witnesses the
coupling reaction followed by the cluster cleavage.[43] The
loss of TMEDA alone cannot be ascribed to the coupling
reaction from the same reason as described above for the
Figure 4. CID spectrum of [(2-H)2Cu2Cl(TMEDA)]+ at Ecoll = 1.0 eV
(center-of-mass frame) generated by ESI of a CH3OH/CH2Cl2/H2O solu-
tion of 2 and Cu(OH)Cl•TMEDA. Collision gas: xenon
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COPPER CATALYSIS
Figure 5. B3LYP/SDD optimized structures of [(2-H)Cu]+ (E0K = À1672.276663 hartree), its isomer lying 1.74 eV (168 kJ molÀ1) higher in energy, and
their complexes with ethylenediamine [(2-H)Cu(en)]+ (E0K = À1862.701699 hartree). The hydrogen atoms have been removed for the sake of clarity
of the figure
reveals one major difference observed for the mixed
complex. In the homo complexes [(1-H)2Cu2Cl(TMEDA)]+
+
•
•
and [(2-H)2Cu2Cl(TMEDA)] , no eliminations of the (1-H) and (2-H)
radicals are observed. From the fragmentation of the mononuclear
+
•
complex [(1-H)Cu(TMEDA)] , we know that the (1-H) radical can be
formed via the homolytical cleavage of the copper–oxygen bond
(see above). For the binuclear complex [(1-H)2Cu2Cl(TMEDA)]+, how-
ever, the cluster cleavage is more facile than the one-electron
oxidation of (1-H)ˉ, which is hence completely suppressed, and
the two electron oxidation leading to the coupling is observed only
as a minor channel (eliminations of TMEDA and [CuCl(TMEDA)]).
Oxidation of (2-H)ˉ is much more difficult, (c.f. Fig. 1d) and again
for the binuclear cluster [(2-H)2Cu2Cl(TMEDA)]+, only the
concerted two electron oxidation evidenced by the elimination
of CuCl(TMEDA) is observed.
Figure 6. CID spectrum of [(1-H)(2-H)Cu2Cl(TMEDA)]+ at Ecoll = 1.2 eV
(center-of-mass frame) generated by ESI of a CH3OH/CH2Cl2/H2O solution
of 1, 2, and Cu(OH)Cl•TMEDA. Collision gas: xenon
fragmentation of [(2-H)2Cu2Cl(TMEDA)]+. Fragmentation of
the larger complex with two TMEDA ligands, [(1-H)(2-H)
Cu2Cl(TMEDA)2]+, leads dominantly to the loss of one TMEDA
ligand (Fig. S5). Further fragmentation proceeds in analogy to
that of [(1-H)(2-H)Cu2Cl(TMEDA)]+.
For the mixed complex [(1-H)(2-H)Cu2Cl(TMEDA)]+, the second
•
most abundant channel corresponds to the elimination (1-H).
This evidences a larger stability of the mixed binuclear complex
compared to [(1-H)2Cu2Cl(TMEDA)]+. We note in passing that
the stability of the binuclear clusters have a correlation with
the yield in the coupling reaction and can hence contribute here
to the preferential cross-coupling reaction.[28]
Comparison of the spectra of [(1-H)2Cu2Cl(TMEDA)]+,
[(2-H)2Cu2Cl(TMEDA)]+, and [(1-H)(2-H)Cu2Cl(TMEDA)]+
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S. KOscOVÁ, J. ROITHOVÁ AND J. HODAcOVÁ
If we take into the account also binuclear complexes with two
TMEDA ligands, then the elimination of the (1-H) radical is
METHODS
•
observed also for [(1-H)2Cu2Cl(TMEDA)2]+ and [(1-H)(2-H)Cu2Cl
(TMEDA)2]+ (Figs. S4 and S5). The homonuclear [(1-H)2Cu2Cl
(TMEDA)2]+ cluster appears as the most reactive towards the
coupling reaction among the investigated complexes as we
observe not only the one-electron oxidation of the substrate,
but also direct elimination of (1-H)2 (i.e. 3) from the cluster
(i.e. two-electron oxidation) as a significant channel. Hence,
next to the electronic and stability properties of the clusters, also
other factors have to play a role in the preferential cross-coupling
reaction. We have clearly shown that naphthol 2 has a substan-
tially larger affinity to copper ions than naphthol 1. Thus, in an
equimolar mixture of 1, 2, and Cu(OH)Cl•TMEDA, most of the
copper ions will be complexed by 2. For the occurrence of the
coupling reaction, a binuclear cluster has to be formed. Formation
of binuclear clusters [(1-H)2Cu2Cl(TMEDA)]+ will be statistically
disfavored, because most of the copper ions are bound to 2. On
the other hand, formation of [(2-H)2Cu2Cl(TMEDA)]+ in solution
may be slowed down due to the steric reasons and the cluster is
little reactive. As a result, the mixed binuclear clusters
[(1-H)(2-H)Cu2Cl(TMEDA)]+ may represent a compromise
in the abundance and the reactivity, which finally leads
to the preferential cross-coupling.
Mass-spectrometric experiments
The experiments were performed with a TSQ Classic mass spec-
trometer which has been described previously.[44,45] Briefly, the
TSQ Classic consists of an ESI source combined with a tandem
mass spectrometer of QOQ configuration (Q stands for quadru-
pole and O for octopole). The investigated ions were generated
by ESI of solutions of the precursor naphthols in CH2Cl2/CH3OH,
to which either Cu(OH)Cl•TMEDA or Cu(NO3)2 dissolved in water
was added. The first quadrupole was used as a mass filter to scan
the spectrum of the ions produced upon ESI or to select particu-
lar ions of interest. The Q1-selected ions were then guided
through the octopole serving as a collision chamber followed
by mass analysis of the ionic reaction products by means of
the second quadrupole and subsequent detection. Reagent or
collision gases were leaked into the octopole at typical pressures
in the order of 10–4 mbar. The origin of the collision energy scale
was determined using retarding potential field analysis.[45]
Computational details
The computational DFT study was performed using the B3LYP[46–49]
functional together with the SDD basis set as implemented in the
Gaussian 03 package.[50–53] For all optimized structures, frequency
analyses at the same level of theory are used in order to assign
them as genuine minima or transition structures on the poten-
tial-energy surface as well as to calculate zero-point vibrational
energies. The relative energies refer to energies at 0 K. The search
for the minima has been restricted to several conformers. We
intend to show the trends here rather than an exhaustive con-
formational search for global minima, which would be rather
demanding for the given system. The reported spin localizations
at copper atoms were obtained from Mulliken population analysis.
CONCLUSIONS
It is shown that the complexation properties of deprotonated
amides of 2-hydroxy-3-naphthoic acids 1 and 2 toward copper
completely differ. The naphtholate (1-H)ˉ binds to copper(II) as
a bidentate ligand via both oxygen atoms. On the other hand,
due to the crown substituent of (2-H)ˉ, copper(II) binds not
only to the two oxygen atoms of the naphtholate moiety, but
it is also coordinated by the crown backbone. Consequently,
the binding of (2-H)ˉ to copper(II) is much stronger than that
of (1-H)ˉ.
Preparative experiment
The reactivities of the copper complexes [(1-H)Cu(TMEDA)]+
and [(2-H)Cu(TMEDA)]+ differ. While the former is prone to the
one-electron oxidation, the latter is not. This is also reflected in
the reactivities of the binuclear clusters [(1-H)2Cu2Cl(TMEDA)x]+,
[(2-H)2Cu2Cl(TMEDA)]+, and [(1-H)(2-H)Cu2Cl(TMEDA)x]+ (x = 1,2).
The homonuclear [(1-H)2Cu2Cl(TMEDA)2]+ complex appears as
the most reactive one. The preferential cross-coupling can
hence be explained based on an interplay between the larger
abundance of the copper complexes [(2-H)Cu(TMEDA)]+
(based on the larger binding energy) and the larger reactivity
of [(1-H)Cu(TMEDA)]+.
The effect of TMEDA consists in a strong binding to the
complexes of copper and the naphtholates. The coordination
of TMEDA to copper stabilizes its oxidation state + II (i.e. the
unpaired electron is localized at copper) and thereby decreases
the reactivity of the copper complexes of naphtholates for the
reactions as carbon-centered radicals. Hence, it suppresses the
reactivity of [(1-H)Cu(TMEDA)]+ which thus does not react
directly with another naphthol molecule present in the reaction
mixture (i.e. formation of statistical distribution of products
would be expected), but instead implies a necessity of forma-
tion of ad hoc binuclear clusters in order to promote the cou-
pling reaction. As explained above, the necessity of cluster
formation results in the preferential cross-coupling for this
reaction system.
To a mixture of amide 1 (60.4 mg; 2.3Â10À4 mol) and amide 2
(99.5 mg; 2.3Â10À4 mol) in dichloromethane (10 ml), Cu(OH)
Cl·TMEDA (53.3 mg; 2.3Â10À4 mol) was added, and the mixture
was stirred for 71 h at room temperature under the oxygen
atmosphere. The mixture was washed with 6 M-HCl, water, and
5% aqueous NaHCO3, and the dichloromethane solution was
dried over MgSO4. The drying agent was filtered off, and the
solvent was evaporated. The residue was subjected to a column
chromatography (SiO2; eluent: ethylacetate-acetone-ethanol-
water 19:3:2:1) giving products 3 (20 mg; 16%), 4 (116 mg; 73%),
and 5 (11 mg; 5%). The characterization of the compounds is given
in the Supporting Information.
Analytical experiment
Prior to the analytical study, high-performance liquid chroma-
tography (HPLC) analytical conditions for separation of com-
pounds 1–5 were optimized, and absorption coefficients of all
compounds at l = 254 nm were obtained in order to be able to
re-calculate a peak area into a compound quantity. A reaction
was monitored by means of HPLC on a Discovery C18 column
using an eluent gradient from the methanol – water 70:30 mixture
to neat methanol (flowrate 1 ml/min).
To a solution of equimolar mixture of amides 1 and 2
(1.5Â10À5 mol) in dichloromethane (7 ml), one molar equivalent
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COPPER CATALYSIS
[25] M. Hovorka, R. Scigel, J. Günterová, M. Tichý, J. Závada, Tetrahedron
1992, 48, 9503.
of Cu(OH)Cl·TMEDA was added, and the reaction mixture was
stirred at room temperature under the oxygen atmosphere. A
sample of reaction mixture (2 mg) was diluted with methanol
(1ml), and this solution (10 ml) was injected onto the HPLC column.
A progress of the reaction was monitored until the starting amides
disappeared. The reaction was finished after 20 h with the products
molar ratios 3 : 4 : 5 = 9 : 82 : 9.
ꢀ
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[28] J. Roithová, D. Schröder, Chem. Eur. J. 2008, 14, 2180.
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Acknowledgements
[31] P. Milko, J. Roithová, N. Tsierkezos, D. Schröder, J. Am. Chem. Soc.
2008, 130, 7186.
This work was supported by the Grant Agency of the Czech
Republic (108/12/1356 and 207/11/0338), the European Research
Council (StG ISORI) and the Ministry of Education of the Czech
Republic (MSM0021620857).
[32] M. Noji, M. Nakajima, K. Koga, Tetrahedron Lett. 1994, 35, 7983.
[33] Note that the preparative and analytic experiments were done at
different concentrations, which is most probably responsible for
different relative yields. Moreover, the preparative experiment is
influenced by the efficiency of the product isolation. Products 4
and 5 contain the crown substituent, which might lead to higher
losses during the purification of the products.
[34] For selected mass-spectrometric mechanistic studies see:
L. S. Santos, C. H. Pavam, W. P. Almeida, F. Coelho, M. N. Eberlin,
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