[2.2]Paracyclophane-triazolyl monophosphane ligands: Synthesis and their copper and palladium complexes

Article abstract of DOI:10.1002/ejoc.201300031

Triazole-based phosphanes have recently been shown to be interesting ligands in organometallic catalysis. The synthesis of novel [2.2]paracyclophane- substituted triazole-based phosphane ligands was achieved. The possibility to synthesize these molecules in a highly enantioenriched form is also reported. Moreover, the ability of the novel ligands to coordinate with metal centers was explored. Besides a dinuclear copper complex, a Pd^II complex could also be isolated, the structure of which was characterized by X-ray analysis. Pd^II complexes derived from these ligands provide highly active catalysts for the Suzuki-Miyaura coupling of aryl chlorides. Novel triazole-based phosphane ligands were obtained from ethynyl- or azido[2.2]paracyclophane through a modular approach. Their coordination to metals was explored, and a Pd^II complex was characterized by X-ray analysis. Application of these ClickPhos ligands in the Pd-catalyzed Suzuki-Miyaura coupling of aryl chlorides is also reported. Copyright

Full text of DOI:10.1002/ejoc.201300031

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DOI: 10.1002/ejoc.201300031
[2.2]Paracyclophane–Triazolyl Monophosphane Ligands: Synthesis and Their
Copper and Palladium Complexes
Martina Austeri,[a] Mirja Enders,[a] Martin Nieger,[b] and Stefan Bräse*[a]
Keywords: ClickPhos / Phosphane ligands / Cyclophanes / Cross-coupling / Chirality
Triazole-based phosphanes have recently been shown to be
interesting ligands in organometallic catalysis. The synthesis
of novel [2.2]paracyclophane-substituted triazole-based
phosphane ligands was achieved. The possibility to synthe-
size these molecules in a highly enantioenriched form is also
reported. Moreover, the ability of the novel ligands to coordi-
nate with metal centers was explored. Besides a dinuclear
copper complex, a PdII complex could also be isolated, the
structure of which was characterized by X-ray analysis. PdII
complexes derived from these ligands provide highly active
catalysts for the Suzuki–Miyaura coupling of aryl chlorides.
Introduction
In the development of novel potent catalysts to enhance
organic transformations, the choice and design of the ligand
are of great importance. As is well known, phosphane-
based molecules are ligands of choice in many different or-
ganometallic-catalyzed processes. Recently, it was shown
that triazole-substituted phosphane ligands are promising
structures that can be successfully used in palladium cataly-
sis.[1] Following the reliable procedure of Sharpless for the
synthesis of triazoles,[2] Zhang reported the first synthesis
of the ClickPhos family of ligands[3] (1, Figure 1). His
group also showed an elegant application of these ligands
in the Suzuki–Miyaura reaction. Recently, our group re-
ported a convenient one-step synthesis for molecules of this
type[4] and their use in the formation of metal complexes.
Specifically, the prepared copper complexes showed signifi-
cant luminescent properties.[5]
Figure 1. General structure of ClickPhos ligand family 1 and both
enantiomers of the [2.2]paracyclophane moiety.
odologies for the resolution or enantioselective synthesis of
some paracyclophane derivatives have already been re-
ported, and this provides the possibility to use these mole-
cules as intermediates for the synthesis of novel enantiopure
ligands. However, to the best of our knowledge, there is no
report on triazolyl-functionalized paracyclophanes.
We herein report the synthesis of novel [2.2]paracyclo-
phane-derived ClickPhos-like ligands and their application
in the formation of metal complexes and catalysis.
At this stage, our interest laid in the synthesis and study
of similar structures that were additionally chiral, and this
would possibly allow the formation of enantiopure metal
complexes. As a chiral unit, we considered the [2.2]paracy-
clophane scaffold as an optimal choice (Figure 1). As a re-
sult of the large number of possibilities to functionalize the
core structure, this framework has already been used in the
synthesis of rigid planar–chiral ligands.[6] Moreover, meth-
Results and Discussion
As a first step, we envisaged the possibility to synthesize
a paracyclophane-substituted 1,2,3-triazole following the
procedure of Sharpless.[2] For this purpose, azido[2.2]para-
cyclophane (2) was easily obtained from the reaction of
bromo[2.2]paracyclophaneϪreadily available from the par-
ent [2.2]paracyclophane by brominationϪwith tosyl azide
in the presence of n-butyllithium.[7] Azide 2 was then added
to the in situ generated bromomagnesium phenylacetylide
to obtain corresponding 1,5-disubstituted 1,2,3-triazole 1a
(Scheme 1). After some experimentation, the desired tri-
azole could be obtained in 50% yield by performing the
reaction at a concentration of 2 m in THF. The next step of
the ClickPhos synthesis was the addition of the phosphane
moiety to triazole 1a (Scheme 1) following the procedure
of Zhang.[3] This transformation was performed by initial
[a] Institute for Organic Chemistry, Karlsruhe Institute of
Technology (KIT),
Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
Fax: +49-721-608-8581
E-mail: braese@kit.edu
Homepage: www.ioc.kit.edu
[b] Laboratory of Inorganic Chemistry, Department of Chemistry,
University of Helsinki,
P. O. Box 55 (A.I. Virtasen aukio 1), 00014 University of
Helsinki, Finland
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300031.
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M. Austeri, M. Enders, M. Nieger, S. Bräse
SHORT COMMUNICATION
lithiation of triazole 1a in THF with lithium diisoprop- 4 with EtMgBr and subsequent addition of the correspond-
ylamide, and the subsequent addition of an excess amount ing azide (phenyl azide and 4-nitrophenyl azide, respec-
of diphenylphosphanyl chloride. Corresponding diphenyl- tively). Following this procedure, desired molecule 1b could
triazolylphosphane 3a was obtained as the major product be isolated in higher yield (80%, Scheme 3), whereas modi-
of the reaction and could be isolated in good yield (65%).[8] fied compound 1c was obtained in moderate yield (26%,
Despite the fact that a new stereogenic axis was formed, in Scheme 3). Also, the following substitution step with aryl-
this and all other cases below only one isomer originating phosphanyl chlorides was performed similarly to the syn-
from this axis was formed (see also Figure 2).
thesis of ligand 3a, and desired ClickPhos-type ligands 3c
and 3d were successfully isolated, but unfortunately only
in moderate yields (40 and 34%, respectively). During the
optimization process, we also observed products derived
from nonselective metalation. The sites of metalation have
not been fully established because of the complexity of the
NMR spectra and will be the subject of further investi-
gations. However, by using the optimized conditions de-
scribed above, these side products were not isolated.
Scheme 1. Synthesis of triazole 1a and ClickPhos-like ligand 3a.
Delighted by this result, we decided to attempt the syn-
thesis of the tris(triazolyl)phosphane bearing one paracy-
clophane substituent on each triazole fragment (i.e., 3b;
Scheme 2). This reaction was performed in a manner sim-
ilar to that of the preceding example, but in this case, PCl3
(1.1 equiv.) was added to the in situ generated lithium–tri-
azole species (3 equiv.). Desired ClickPhos-like ligand 3b
was obtained after chromatography as a mixture of dia-
stereomers in a ratio of 3:1, because of the fact that the
paracyclophane–triazole employed was racemic (theoretical
ratio 3:1). When the two diastereomers were separated by
silica gel column chromatography, the major and minor dia-
stereomers were isolated in 19 and 12% yield, respectively.
Notably, they are not air stable. This is the first example
of a C3-symmetric paracyclophane system.[9] As would be
expected for the homochiral isomer, the minor isomer dis-
Scheme 3. Synthesis of triazoles 1b and 1c and ClickPhos-like li-
gands 3c and 3d.
Moreover, thanks to efficient methodology for the reso-
lution of the racemic formyl[2.2]paracyclophane (already
reported by our group),[12] we could also synthesize phos-
phane (Sp)-3c in a highly enantioenriched form [starting
from (Sp)-formyl[2.2]paracyclophane with 98%ee]. No-
tably, the stereogenic elements are in this case closer to the
phosphorus atom.
1
plays a clearer H NMR spectrum.
With these molecules in hand, we decided to test their
properties in the synthesis of metal complexes. Our group
recently showed that copper complexes with triazolyl–phos-
phane ligands have interesting photoluminescence proper-
ties.[4,5] Therefore, we chose to react equimolar quantities of
ligand 3a and CuI as the metal source in dichloromethane
Scheme 2. Synthesis of ClickPhos-like ligand 3b.
To broaden the spectrum of paracyclophane-derived li- (Scheme 4). The complexation was accomplished after a
gands, we altered the structure to obtain the paracyclo- few hours, and desired metal complex 5 could be obtained
phane substituent in the 5-position of the triazole. In this after precipitation in pentane and subsequent filtration of
case, the chiral substituent would be closer to the phos- the white solid. This complex was then analyzed by 31P
phorus atom. For this reason, following the procedure of NMR spectroscopy, and a clear shift of the phosphane sig-
Guyard and Knorr,[10] ethynyl[2.2]paracyclophane (4)[11] nal with respect to the free ligand was observed. High-reso-
was synthesized in a two-step procedure by a Corey–Fuchs lution mass spectrometry showed that a dinuclear metal
transformation starting from racemic formyl[2.2]paracyclo- complex of the type L2Cu2I2 was obtained, which is in good
phane (see the Supporting Information). Corresponding tri- accordance with the previously described results[4] (see the
azoles 1b and 1c were then synthesized by reaction of rac- Supporting Information).
2
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[2.2]Paracyclophane–Triazolyl Monophosphane Ligands
Scheme 4. Synthesis of complexes 5 and 6.
At this stage, we wondered if the same ligand could be
used to synthesize complexes in the presence of metals of
different nature. In this regard, palladium was chosen as a
test metal, in consideration of the wide application of this
metal and its complexes in organometallic catalysis, also for
ClickPhos ligands.[1] The complexation was performed by
mixing bis(acetonitrile)palladium(II) chloride (1 equiv.) and
ligand 3a (2 equiv.) in dichloromethane (Scheme 4). Also in
this case, complex 6 was isolated by precipitation in pentane
and following filtration of the yellow solid. Single crystals
suitable for X-ray diffraction analysis were obtained by slow
diffusion of ethyl acetate into a solution of the complex in
CDCl3. The structure of complex 6 is shown in Figure 2.[13]
As also suggested by HRMS analysis, the complex is of
L2PdCl2 stoichiometry, and the two ligands are coordinated
to the metal center through the phosphorus atoms. Com-
plex 6 possesses crystallographic Ci symmetry. The Pd atom
is square-planar and is coordinated with a trans configura-
tion of the Cl atoms and the [2.2]paracyclophane–triazolyl-
phosphane ligands. Analysis of this molecule by 31P NMR
spectroscopy shows the presence of two sets of signals,
which are due to the presence of two possible diastereomers
(meso and rac) in solution, but only oneϪthe racemic iso-
merϪcrystallized. To the best of our knowledge, this is the
first ClickPhos palladium complex with a P–Pd bond.
In the next step, we evaluated the catalytic activity of new
ClickPhos ligands rac-3c and 3d. The Pd-catalyzed Suzuki–
Miyaura coupling of 4-chlorotoluene (7) with phenylbor-
Figure 2. Molecular structure of complex 6 (displacement param-
eters are drawn at the 50% probability level, H atoms omitted for
clarity). Selected bond lengths [Å] and angles [°]: Pd1–P1 2.306(1),
Pd1–Cl1 2.300(1), Cl1–Pd1–P1 92.96(4), Cl1a–Pd1–P1 87.04(4).
Table 1. Screening of the ligands.[a]
Entry
Ligand
Conversion of 8[b]
Yield [%][b]
1
2
3
rac-3a
rac-3c
rac-3d
quant.
quant.
quant.
0[c]
20[c]
88
[a] Reaction conditions: 4-chlorotoluene (7, 1 mmol), phenylbor-
onic acid (8, 1.5 mmol), K3PO4 (2 mmol), Pd(dba)2 (1 mol-%), li-
gand 3 (2 mol-%), toluene (3 mL), 12 h, 80 °C. [b] Detected by GC–
MS of the crude product. [c] The main product was the homocou-
pled product derived from 8.
Conclusions
New chiral [2.2]paracyclophane-substituted triazoles
onic acid (8) served as a test reaction for our new ligands could be synthesized by using Click-type chemistry. These
(Table 1).[3]
molecules could then be further functionalized to obtain
The reactions were performed with Pd(dba)2 (1 mol-%) ClickPhos-type ligands such as monotriazolylphosphane
and ligand rac-3a, 3c, or 3d (2 mol-%). As expected, the and tristriazolylmonophosphane. Containing a [2.2]paracy-
reaction of a deactivated aryl chloride with rather electron- clophane substituent, these molecules are planar–chiral,
poor diphenylphosphane ligand rac-3a did not deliver de- and the possibility to obtain them in a highly enantio-
sired product 9, but the main product was biphenyl, which enriched form was successfully explored. Also, the ability
was derived from phenylboronic acid (8).[14] With ligand of the monotriazolylphosphane to coordinate to metal cen-
rac-3c, product 9 was indeed obtained, but only in low yield ters was studied, and a dinuclear CuI complex and a mono-
(Table 1, entry 2). Using more electron-rich ligand rac-3d, nuclear PdII complex could be synthesized. In the case of
the yield increased up to 88%. These results are in good the palladium complex, the structure was elucidated
agreement with literature values for comparable catalyst through X-ray crystal analysis. First studies regarding their
systems[3] and prove the catalytic potential of our ClickPhos application in catalysis have shown the catalytic potential of
ligands.
these new compounds. Further optimization of the reaction
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M. Austeri, M. Enders, M. Nieger, S. Bräse
SHORT COMMUNICATION
[6] a) G. J. Rowlands, Isr. J. Chem. 2012, 52, 60–75; b) J. Paradies,
Synthesis 2011, 3749–3766; c) S. E. Gibson, J. D. Knight, Org.
Biomol. Chem. 2003, 1, 1256–1269.
[7] R. J. Seacome, M. P. Coles, J. E. Glover, P. B. Hitchcock, G. J.
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[8] In the case of [2.2]paracyclophanyl azides and alkynes, the two-
step synthesis gave better results than the convenient one-pot
procedure described in ref.[4]
[9] a) B. E. Frauhiger, J. L. Templeton, Organometallics 2012, 31,
2770–2784; b) B. E. Frauhiger, P. S. White, J. L. Templeton, Or-
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Organometallics 2008, 27, 3210–3215.
[10] S. Clément, L. Guyard, M. Knorr, S. Dilsky, C. Strohmann,
M. Arroyo, J. Organomet. Chem. 2007, 692, 839–850.
[11] For this and other ethynyl[2.2]paracyclophanes, see: a) H.
Hopf, I. Dix, V. Raev, L. Ernst, Eur. J. Org. Chem. 2012, 1653–
1655; b) L. Bondarenko, I. Dix, H. Hinrichs, H. Hopf, Synthe-
sis 2004, 2751–2759; c) A. A. Aly, Tetrahedron 1993, 49, 7325–
7336.
conditions as well as asymmetric Pd-catalyzed cross-cou-
pling reactions with enantiopure ligands of this type will be
explored.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures, characterization data, crystallo-
graphic data of complex 6, and 1H NMR and 13C NMR spectra
of all synthesized compounds.
Acknowledgments
Financial support from the Karlsruhe Institute of Technology
(KIT) is acknowledged. The authors thank the Deutsche For-
schungs-gemeinschaft (DFG) for support through project B2 of
SFB/TRR 88 (“Kooperative Effekte in homo- und heterometal-
lischen Komplexen”). Daniel Zink is thanked for valuable advice.
Dr. Pavleta Tzvetkova is greatly acknowledged for valuable assist-
ance in NMR spectroscopy.
[12] C. J. Friedmann, S. Ay, S. Bräse, J. Org. Chem. 2010, 75, 4612–
4614.
[1] Q. Dai, W. Gao, D. Liu, L. M. Kapes, X. Zhang, J. Org. Chem.
2006, 71, 3928–3934.
[13] CCDC-905227 contains the supplementary crystallographic
data for 6. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[2] A. Krasin´ski, V. V. Fokin, K. B. Sharpless, Org. Lett. 2004, 6,
1237–1240.
[3] D. Liu, W. Gao, Q. Dai, X. Zhang, Org. Lett. 2005, 7, 4907–
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[4] D. M. Zink, T. Baumann, M. Nieger, S. Bräse, Eur. J. Org.
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[5] D. M. Zink, T. Grab, T. Baumann, M. Nieger, E. C. Barnes,
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[14] For the O2-promoted homocoupling of boronic acid, see J. P.
Parrish, Y. C. Jung, R. J. Floyd, K. W. Jung, Tetrahedron Lett.
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Received: October 14, 2012
Revised Version Received: January 9, 2013
Published Online: ᭿
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[2.2]Paracyclophane–Triazolyl Monophosphane Ligands
Chiral ClickPhos Ligands
Novel triazole-based phosphane ligands
were obtained from ethynyl- or azido[2.2]-
paracyclophane through a modular ap-
proach. Their coordination to metals was
explored, and a PdII complex was charac-
terized by X-ray analysis. Application of
these ClickPhos ligands in the Pd-catalyzed
Suzuki–Miyaura coupling of aryl chlorides
is also reported.
M. Austeri, M. Enders, M. Nieger,
S. Bräse* ........................................... 1–5
[2.2]Paracyclophane–Triazolyl Monophos-
phane Ligands: Synthesis and Their Cop-
per and Palladium Complexes
Keywords: ClickPhos / Phosphane ligands /
Cyclophanes / Cross-coupling / Chirality
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