On the origin of copper(i) catalysts from copper(ii) precursors in C-N and C-O cross-couplings

Article abstract of DOI:10.1039/c0dt00632g

Cu^II precursors ligated to phenanthrolines are reduced in situ by alcohols or amines in the presence of a base (Cs₂CO₃) to generate Cu^I species which are active catalysts in C-N and C-O cross-coupling reactions. The conversion Cu^II → Cu^I has been evidenced and monitored by UV-vis and NMR spectroscopy.

Full text of DOI:10.1039/c0dt00632g

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On the origin of copper(I) catalysts from copper(II) precursors in C–N and
C–O cross-couplings†
Gre´gory Franc and Anny Jutand*
Received 10th June 2010, Accepted 9th July 2010
First published as an Advance Article on the web 2nd August 2010
DOI: 10.1039/c0dt00632g
CuII precursors ligated to phenanthrolines are reduced in situ
by alcohols or amines in the presence of a base (Cs2CO3)
to generate CuI species which are active catalysts in C–N
to those of catalytic reactions (same CuII precursors, same dative
N,N ligands, same N- or O-nucleophiles and same base).
Owing to expected different colors for CuII and CuI complexes,
UV-vis spectroscopy was used to follow an assumed CuII → CuI
conversion in solution. The ligand 1,10-phenanthroline (phen)
was first selected because the CuI complex: (phen)2Cu+17 and the
CuII complex: (phen)2Cu2+18 are well-known, as are their UV-vis
absorbance properties.17,18 In addition, phen or substituted phen
are successfully associated to copper in catalytic cross-coupling
reactions.3,5,8,10,11,13 Addition of 2 equiv. of phen to a solution of
either CuI or CuBr (0.1 mM) in DMF into a UV cell, gave a deep-
red solution characteristic of the CuI complex: (phen)2Cu+.17 Its
UV-vis spectrum exhibited an absorption band at lmax = 445 nm.17
The UV-vis spectrum of a pale green solution of CuBr2 (0.9 mM)
and C–O cross-coupling reactions. The conversion CuII
→
CuI has been evidenced and monitored by UV-vis and NMR
spectroscopy.
Metal-catalyzed cross-coupling reactions between aryl halides and
amines or alcohols in the presence of a base are of tremendous
interest for products relevant to both academic research and
industry (Scheme 1).
and phen (2 equiv.) exhibited a broad absorption band at lmax
=
746 nm (Fig. 1, red curve) characteristic of the CuII complex:
(phen)2Cu2+.18
Scheme 1 Metal-catalyzed C–N and C–O cross-coupling reactions.
Palladium represents one of the most efficient catalysts for
such cross-coupling reactions. However, sophisticated expensive
phosphines are often required.1 In the early 2000s, several groups
developed copper catalysts associated to dative N,N ligands, as
efficient and cheaper alternatives for C–N 2–8 and C–O 2,8–13 cross-
coupling reactions.
From experimental works, CuI species (CuI, CuBr, Cu2O, Cu+)
are generally found to be the most efficient catalysts2–13 and
mechanistic studies also consider that CuI species are involved
in the very first steps of the catalytic cycles.4–6,13 However, catalytic
systems employing CuII (CuBr2, CuCl2, CuO) or Cu0 as precursors
may also generate positive results.2,7,9 A question arises: how can
three different oxidation states Cu0, CuI and CuIIperform such
a task? We recently elucidated the case of Cu0 which was found
to be a precursor of CuI catalyst by activation of aryl halides by
electron transfer in the very first step of catalytic reactions.14 The
activity of CuII precursor remains unclear. CuII-catalyzed C–O and
C–N bonds formations are usually slower2 than those catalyzed
by CuI suggesting that a pre-reaction takes place in which the CuII
precursor slowly delivers the active CuI catalyst. To explain such
phenomenon, it has been proposed that CuII could be reduced
to CuI by the nucleophiles (e.g., Ph2N-,15 RO-16) in the absence
of any ligand, but no clear-cut evidence is currently available
when a dative N,N ligand is used. Mechanistic clarifications are
given in the present work on the formation of CuI species from
CuII precursors, under experimental conditions which are close
Fig. 1 UV-vis spectra in a 1 cm UV cell of (phen)2Cu2+ generated from
CuBr2 (0.9 mM) and 1,10-phenanthroline (1.8 mM) in 3 mL of DMF at at
room temperature (red curve). Addition of PhCH2OH (12 mM) followed
by Cs2CO3 (12 mM) resulted in the fast appearance of (phen)2Cu+ (blue
curves). The final spectrum (upper one) was obtained after 30 min.
Nucleophilic reagents used in catalytic C–O or C–N cross-
coupling reactions (alcohol or amines respectively) were then
added to solutions of (phen)2Cu2+ (0.9 mM in DMF) to test
the expected transformation: CuII → CuI. At first, the spectrum
of (phen)2Cu2+ was not affected by addition of benzyl alcohol
(12 mM) but a dramatic change appeared after addition of a base,
as required in all catalytic reactions (Scheme 1). The base Cs2CO3
was selected and added as a solid (formally 12 mM). Just after
its addition, the absorption band characteristic of (phen)2Cu2+
disappeared with time whereas the absorption band of (phen)2Cu+
at 445 nm increased meanwhile (Fig. 1). Total conversion of
(phen)2Cu2+ was achieved within 30 min, but the formation of
(phen)2Cu+ was not quantitative (47% yield). Similar yield was
UMR CNRS-ENS-UPMC 8640. Ecole Normale Supe´rieure, De´partement
de Chimie, 24 rue Lhomond, F-75231, Paris Cedex 5, France. E-mail:
Anny.Jutand@ens.fr; Fax: +33 144322402; Tel: +33 144323872
† Electronic supplementary information (ESI) available: NMR spectra.
See DOI: 10.1039/c0dt00632g
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Dalton Trans., 2010, 39, 7873–7875 | 7873
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obtained (40%) in another experiment performed from CuBr2 at
lower concentration (0.7 mM).
instability of the transient intermediate Cu0. Indeed, a previous
study by cyclic voltammetry established that the Cu0 generated by
reduction of (phen)2Cu+ was not very stable in acetonitrile.14 In
the present reactions, the unstable Cu0 could be “quenched” by
(phen)2Cu2+ to generate (phen)2Cu+ but not quantitatively (path
(a), Scheme 2). The observed yields (below 50%) confirmed the
instability of the Cu0 intermediate.
The same CuII → CuI conversion was observed upon addition
of excess benzylamine (Fig. 2) or cyclohexylamine to (phen)2Cu2+,
followed by Cs2CO3. It is worthwhile noting that addition of
benzyl amine first led to the fast and complete formation of an
intermediate CuII complex at lmax = 690 nm which slowly evolved
to (phen)2Cu+ only after addition of the base (Fig. 2). The same be-
havior was observed for cyclohexylamine. The slowest and lowest
CuII → CuI conversion was observed for the cyclohexylamine.
In contrast to benzyl alcohol which can be slowly deprotonated
by Cs2CO3 to generate the corresponding alkoxide,20 the depro-
tonation of amines needs stronger bases. A pre-coordination of
the amine onto (phen)2Cu2+ to afford a stable penta-coordinated
CuII complex (PhCH2NH2)(phen)2Cu2+ was evidenced by a hyp-
sochromic shift of lmax from 746 to 690 nm (Fig. 2) (from 746 to
630 nm for cyclohexylamine). The protons of a ligated amine
are more acidic than those of the free one.23 Deprotonation
of the ligated amine by the base23 generated a CuII-amido
derivative prompted to undergo b-hydride elimination (Scheme 2).
The formation of Cu0 from CuII via a b-hydride elimination is
supported by the fact that the reaction involving cyclohexylamine
was slower than that involving benzylamine (one H instead of two
Hs in a b-position in the CuII-amido intermediates, respectively).
In catalytic reactions, the intermediate Cu0 generated from CuII
will be able to activate aryl halides by electron transfer to generate
CuI (path (b), Scheme 2), as established in a previous work with
the same phen ligand.14 Such reaction may compete with the
comproportionation. Therefore, CuI moieties can be generated
in situ from Cu0 precursors and CuII precursors as well, at room
temperature.
Fig. 2 UV-vis absorption spectrum in a 1 cm UV cell of CuBr2 (0.9 mM)
and 1,10-phenanthroline (1.8 mM) in DMF at room temperature (red
curve). Addition of benzylamine (12 mM) and then Cs2CO3 (12 mM)
resulting in the slow appearance of a (phen)2CuI+ (blue curves). Saturation
was observed after 90 min.
In order to explore the scope of the transformation, a series of
dative N,N-ligands was tested using benzylalcohol/Cs2CO3, the
most efficient reducing system, following the same UV-vis protocol
described above in DMF. Introduction of substituents onto the
ligand as in 3,4,7,8-tetramethyl-1,10-phenanthroline (Me4-phen)
allowed the desired CuII → CuI transformation, although with a
moderated yield (20%). The initial CuII-complex, (Me4-phen)2Cu2+
(lmax = 737 nm) led to the CuI species (Me4-Phen)2Cu+ (lmax = 434
nm). As far as 2,2¢-bipyridine (bipy) is concerned, the absorption
band of (bipy)2Cu2+ (lmax = 745 nm)18 did disappear after addition
of the benzyl alcohol and base but no (bipy)2Cu+ could be observed
at the expected lmax = 440 nm. Instead an absorption band was
observed at lmax = 620 nm which might characterize a CuII-
alkoxide that was not able to undergo b-hydride elimination. This
is probably why the ligand bipy is directly associated to CuI in
catalytic C–O cross-coupling reactions.12 Addition of two equiv. of
DMEDA (dimethylethylenediamine) to CuBr2 gave a CuII complex
but its absorption band at lmax = 625 nm did not decrease after
addition of benzyl alcohol and Cs2CO3 in excess, indicating that
CuI cannot be generated from a CuII precursor ligated to DMEDA
under our experimental conditions at room temperature.24
In conclusion, CuII precursors associated to phenanthrolines
generate CuI species active in C–N and C–O cross-coupling
reactions. The conversion CuII → CuI has been monitored
by UV-vis spectroscopy and 1H NMR. The known complex
(phen)2Cu+ is generated from the known complex (phen)2Cu2+
after addition of an alcohol or amines in the presence of a base,
through a process involving a b-hydride elimination followed
by a comproportionation. Therefore, CuII precursors as well as
Cu0 associated to phenanthrolines are a source of CuI species in
catalyzed C–O and C–N bonds formation reactions.
It is well-known that PdII salts or complexes deliver Pd0 species
by reaction with alkoxides or alcohols RCH2OH in the presence
of a base (e.g., K2CO3, Cs2CO3).19,20 Such reactions proceed via b-
hydride elimination from XPdII-OCH2R (X = OAc, Cl). A similar
mechanism is now proposed for a first conversion CuII → Cu0 from
the CuII complex coordinated to the benzyl alkoxide (Scheme 2).21
The b-hydride elimination generated benzaldehyde whose forma-
1
tion in situ was confirmed by H and 13C NMR performed in
DMF-d7.22 The b-hydride elimination from (phen)2CuII-OCH2Ph+
and the subsequent deprotonation of the CuII-hydride by the base
must be fast since those intermediates were not detected on the
UV-vis spectrum. The resulting Cu0 could then be involved in
a comproportionation16 with the initial CuII species (path (a) in
Scheme 2) to generate a CuI moiety ligated by phenanthroline,
(phen)2Cu+, as clearly observed by UV-vis spectroscopy (Fig. 1).
The non quantitative conversion CuII → CuI could be due to the
Scheme 2 Paths leading to reactive CuI species starting from CuII (or
from Cu0).
7874 | Dalton Trans., 2010, 39, 7873–7875
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11 A. Tlili, N. Xia, F. Monnier and M. Taillefer, Angew. Chem., Int. Ed.,
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Acknowledgements
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22 CuBr2 (4.3 mg, 0.022 mmol), phenanthroline (7.5 mg, 0.044 mmol),
PhCH2OH (4.5 mL, 0.044 mmol) and Cs2CO3 (28.6 mg, 0.088 mmol)
were added successively to 0.5 mL of DMF-d7. At this concentration
(45 mM), the (phen)2Cu2+ was quite insoluble and (phen)2Cu+ slightly
soluble. Indeed, the solution became deep-red, attesting to the forma-
tion of (phen)2Cu+ in low concentration which was not detected in 1H
NMR. PhCH2OH in excess and PhCHO were detected in the deep-red
solution by 1H NMR. Characterization of benzaldehyde after 60 h in
1
the unstirred NMR tube: H NMR (250 MHz, DMF-d7): d 10.13 (s,
1H, CHO), 7.99 (d, J = 7.5 Hz, 2H, o-H), 7.18 (t, J = 7 Hz, 1H, p-H),
7.67 (t, J = 7.2 Hz, 2H, m-H). A shift of 0.13 ppm towards lower field
was observed in DMF-d7 for all signals when compared to those of an
authentic sample in CDCl3. 13C NMR (63 MHz, DMF-d7):d 193.06
(C O). See Fig. S1†.
23 For deprotonation of amines ligated to PdII complexes see: J. Louie and
J. F. Hartwig, Angew. Chem., Int. Ed. Engl., 1996, 35, 2359; T. E. Barder
and S. T. Buchwald, J. Am. Chem. Soc., 2007, 129, 12003.
24 CuCl2 or CuO have been successfully used in ppm catalyst loading
associated with a large amount of DMEDA for C–N cross-couplings
◦
performed at high temperatures (135 C).7 According to the authors,
the high temperature could be at the origin of the formation of
active CuI species which could not aggregate due to the excess of
DMEDA.
This journal is
The Royal Society of Chemistry 2010
Dalton Trans., 2010, 39, 7873–7875 | 7875
©