Covalent modification of diruthenium alkynyl compounds: Novel application of click reactions in organometallic chemistry

Article abstract of DOI:10.1021/om0501632

Diruthenium alkynyl compounds containing one or two 1,2,3-triazoles were prepared via the Cu(I)-catalyzed 1,3-dipolar cycloaddition reaction (click reaction). Electrochemical, magnetic, and molecular structural features of the click products indicate that

Full text of DOI:10.1021/om0501632

2564
Organometallics 2005, 24, 2564-2566
Covalent Modification of Diruthenium Alkynyl
Compounds: Novel Application of Click Reactions in
Organometallic Chemistry
Guo-Lin Xu and Tong Ren*
Department of Chemistry, University of Miami, Coral Gables, Florida 33146
Received March 7, 2005
Summary: Diruthenium alkynyl compounds containing
one or two 1,2,3-triazoles were prepared via the Cu(I)-
catalyzed 1,3-dipolar cycloaddition reaction (click reac-
tion). Electrochemical, magnetic, and molecular struc-
tural features of the click products indicate that peripheral
modification with the 1,2,3-triazole substituent induces
minimal changes in both the molecular structure and
electronic properties of Ru2 alkynyl compounds.
the facile charge mobility across the conjugated back-
bone,8 these metal alkynyl compounds are excellent
electrophores and chromophores and, hence, are ideal
as the reporter group for chemical and biochemical
sensors. As the first step toward the long-term goal of
Ru2 alkynyl biosensors, we have begun to examine the
applicability of the Cu(I)-catalyzed azide alkyne reaction
to Ru2 alkynyl compounds and preliminary results are
reported herein.
Methodologies for conjugation of biological systems
with transition-metal complexes have attracted im-
mense interest in recent years.1,2 The majority of
research efforts have focused on ferrocene modification
of biomolecules, while the use of other metal centers
such as Ru, Cu, and Zn is also known.1,2 Recently, the
Cu(I)-catalyzed 1,3-dipolar cycloaddition reaction be-
tween an alkyne and an organic azide,3 a click reaction,
has gained tremendous popularity and been applied to
the field of chemistry, biology, and materials science,
owing to its exclusive regioselectivity, expansive sub-
strate scope, mild reaction conditions, and very high
yields.4 While the Cu(I)-catalyzed azide alkyne reaction
is most often applied to the field of organic/bioorganic
chemistry, its application to inorganic/organometallic
species is rare. To the best of our knowledge, there are
only two examples involving inorganic/organometallic
species: the synthesis of ferrocene carbohydrate conju-
gates by Santoyo-Gonza´lez5 and the in situ ferrocene
functionalization of electrode surfaces by Collman and
Chidsey.6
With the recent success in postmetalation ligand
modification of diruthenium alkynyl compounds, our
initial attempt in the application of the click reaction
was based on Ru2(DmAniF)3(DMBA-4-C2H)Cl (1a in
Scheme 1; DmAniF is N,N′-di(m-methoxyphenyl)-
formamidinate and DMBA-4-C2H is N,N′-dimethyl-4-eth-
ynylbenzamidinate), where the terminal ethyne is lo-
cated on the periphery of the DMBA ligand.9 The click
reaction between 1a and PhCH2N3 in a solution of
ButOH and H2O in a 2:1 ratio (v/v) using 5 mol % CuSO4
and 10 mol % sodium ascorbate afforded the anticipated
Ru2-containing click product 2a in excellent yields
(quantitative in situ; 63% purified). Purification of 2a
was achieved by simple extraction with CH2Cl2 from the
reaction mixture, and the compound was authenticated
by FAB-MS and elemental analysis. To date, attempts
to crystallize 2a have been unsuccessful.
Similar to the previously established alkynylation
chemistry of diruthenium compounds,7 the reaction
between 2a and 10 equiv of LiC4SiMe3 resulted in the
bis(butadiynyl) compound 4a. Compound 4a was suc-
cessfully crystallized and characterized by X-ray dif-
fraction,10 and its structural plot is presented in Figure
1 along with some selected geometric parameters. The
overall geometry of the Ru2 core in molecule 4a is quite
similar to those of Ru2(DmAniF)3(DMBA-4-X)(C4SiMe3)2
type compounds (X ) I, CtCSiiPr3).9 The geometry of
Our laboratory has reported many Ru2 alkynyl com-
pounds, with an emphasis on their applications as
electronic and optoelectronic materials.7 In addition to
* To whom correspondence should be addressed. E-mail: tren@
miami.edu. Tel. (305) 284-6617. Fax (305) 284-1880.
(1) Severin, K.; Bergs, R.; Beck, W. Angew. Chem., Int. Ed. 1998,
37, 1634.
(2) van Staveren, D. R.; Metzler-Nolte, N. Chem. Rev. 2004, 104,
5931.
(3) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
Angew. Chem., Int. Ed. 2002, 41, 2596.
(4) (a) Lewis, W. G.; Magallon, F. G.; Fokin, V. V.; Finn, M. G. J.
Am. Chem. Soc. 2004, 126, 9152. (b) Chan, T. R.; Hilgraf, R.; Sharpless,
K. B.; Fokin, V. V. Org. Lett. 2004, 6, 2853. (c) Zhou, Z.; Fahrni, C. J.
J. Am. Chem. Soc. 2004, 126, 8862. (d) Wu, P.; Feldman, A. K.; Nugent,
A. K.; Hawker, C. J.; Scheel, A.; Voit, B.; Pyun, J.; Frechet, J. M. J.;
Sharpless, K. B.; Fokin, V. V. Angew. Chem., Int. Ed. 2004, 43, 3928.
(e) Feldman, A. K.; Colasson, B.; Fokin, V. V. Org. Lett. 2004, 6, 3897.
(f) Helms, B.; Mynar, J. L.; Hawker, C. J.; Frechet, J. M. J. Am. Chem.
Soc. 2004, 126, 15020. (g) Sivakumar, K.; Xie, F.; Cash, B. M.; Long,
S.; Barnhill, H. N.; Wang, Q. Org. Lett. 2004, 6, 4603.
(5) Casas-Solvas, J. M.; Vargas-Berenguel, A.; Capitan-Vallvey, L.
F.; Santoyo-Gonzalez, F. Org. Lett. 2004, 6, 3687.
(8) (a) Ren, T.; Zou, G.; Alvarez, J. C. Chem. Commun. 2000, 1197.
(b) Xu, G.-L.; Zou, G.; Ni, Y.-H.; DeRosa, M. C.; Crutchley, R. J.; Ren,
T. J. Am. Chem. Soc. 2003, 125, 10057. (c) Xu, G.-L.; DeRosa, M. C.;
Crutchley, R. J.; Ren, T. J. Am. Chem. Soc. 2004, 126, 3728. (d) Shi,
Y.; Yee, G. T.; Wang, G.; Ren, T. J. Am. Chem. Soc. 2004, 126, 10552.
(9) (a) Chen, W.; Ren, T. Organometallics 2004, 23, 3766.
(10) X-ray diffraction data for crystals 4a and 3c were collected on
a Bruker SMART1000 CCD diffractometer using Mo KR radiation at
300 K. Crystal data for 4a‚2(toluene):
C91H81N11O6Ru2Si2, Mr )
1682.99, triclinic, P1h, a ) 14.3200(6) Å, b ) 16.7241(7) Å, c ) 18.8792-
(8) Å, R ) 99.497(1)°, â ) 98.636(1)°, γ ) 93.273(1)°, V ) 4393.3(3) Å3,
Z ) 2, F ) 1.272 g cm-3. Least-squares refinement based on 8368
reflections with I ) 2σ(I) and 928 parameters led to convergence with
final R1 ) 0.050 and wR2 ) 0.105. Crystal data for 3c‚(toluene)‚0.5-
(benzene):
C93H87N14O6Ru2Si, Mr ) 1727.00, monoclinic, P21/c, a )
(6) Collman, J. P.; Devaraj, N. K.; Chidsey, C. E. D. Langmuir 2004,
20, 1051.
(7) (a) Ren, T.; Xu, G.-L. Comments Inorg. Chem. 2002, 23, 355. (b)
Hurst, S. K.; Ren, T. J. Organomet. Chem. 2003, 670, 188.
22.9842(7) Å, b ) 20.0256(6) Å, c ) 19.5247(6) Å, â ) 98.752(1)°, V )
8882.0(5) Å3, Z ) 4, F ) 1.291 g cm-3. Least-squares refinement based
on 6848 reflections with I ) 2σ(I) and 995 parameters led to
convergence with final R1 ) 0.058 and wR2 ) 0.092.
10.1021/om0501632 CCC: $30.25 © 2005 American Chemical Society
Publication on Web 04/19/2005

Communications
Organometallics, Vol. 24, No. 11, 2005 2565
Scheme 1. Synthetic Routes of the Click Product 2a and Alkynylated Product 4aa
a Legend: (i) CuSO4‚5H2O (5 mol %), sodium ascorbate (10 mol %), PhCH2N3, ButOH/H2O (2:1, v/v); (ii) LiC4TMS (10 equiv),
THF.
Figure 2. ORTEP representation of molecule 3c at the
30% probability level. Selected bond lengths (Å): Ru1-Ru2,
2.4795(7); Ru1-C1, 2.028(7); Ru-N(averaged), 2.035[5];
C(60)-C(61), 1.349(8); N(9)-C(60), 1.360(8); N(9)-N(10),
1.322(8); N(10)-N(11), 1.315(8); N(11)-C(61), 1.339(8);
C(75)-C(76), 1.355(8); N(12)-C(75), 1.357(7); N(12)-N(13),
1.332(6); N(13)-N(14), 1.332(7); N(14)-C(76), 1.327(7).
Figure 1. ORTEP representation of molecule 4a at the
30% probability level. Selected bond lengths (Å): Ru1-Ru2,
2.5509(5); Ru1-C1, 1.962(5); Ru2-C8, 1.957(5); Ru-N(av-
eraged), 2.047[4]; C67-C68, 1.345(7); N(9)-C(67), 1.338-
(7); N(11)-C(68), 1.342(7); N(9)-N(10), 1.319(7); N(10)-
N(11), 1.329(7).
The molecular structure of 3c was established through
a single-crystal X-ray diffraction study, and the forma-
tion of two 1,2,3-triazoles is obvious from its ORTEP
plot (Figure 2). The Ru-Ru bond length in 3c is slightly
shorter than that of Ru2(DmAniF)4(C4SiMe3) (2.506 Å),11
while the Ru-CR and averaged Ru-N bond lengths are
identical. The similarities between the new compounds
reported herein and those based on unfunctionalized
DArF are apparent in physical properties such as
magnetism and optical properties as well. Compounds
of either single chloro or butadiynyl axial ligands,
namely 1a-c, 2a-c, and 3b,c, are paramagnetic with
room-temperature magnetic moments ranging from 3.52
to 3.96 µB, indicating an S ) 3/2 ground state typical of
Ru2L4X (X as halide or alkynyl) type compounds.7
Compounds bearing two axial butadiynyl ligands (4a-
c) are diamagnetic with well-resolved NMR spectra, as
is common to other bis(alkynyl) Ru2(III,III) compounds.
Similar to the diruthenium paddlewheel compounds
previously reported,7,9 all compounds reported herein
are rich in redox activity, and their cyclic voltammo-
grams (CV) are provided in the Suppoting Information.
As an example, the CVs of both compound 4c and the
previously reported Ru2(DmAniF)4(C4SiMe3)211 are shown
in Figure 3. Both compounds exhibit an irreversible
oxidation (A) and two (quasi)reversible reductions (B
and C) with little differences in electrode potentials.
Clearly, the modification of Ru2 alkynyl compounds
through these peripheral click reactions resulted in a
very minimal electronic perturbation.
the 1,2,3-triazole group (C67-C68-N11-N10-N9) in
4a verifies the regiospecificity of the Cu(I)-catalyzed
azide alkyne reaction: trans [2 + 3] cycloaddition
between the terminal acetylene group (-CtCH) and
azide group (-NdNtN).3
The success of the Cu(I)-catalyzed azide alkyne reac-
tion on the periphery of the DMBA ligand encouraged
the extension of the approach to diruthenium species
supported by other N,N′-bidentate ligands containing
peripheral ethyne(s). Specifically, Ru2(DmAniF)3(OAc)-
Cl reacts with either N-phenyl-N′-(4-iodophenyl)form-
amidine (HDPhF1) or N,N′-di(4-iodophenyl)formami-
dine (HDPhF2) to yield either Ru2(DmAniF)3(DPhF1)-
Cl or Ru2(DmAniF)3(DPhF2)Cl, respectively (Supporting
Information). Subsequently, Ru2(DmAniF)3(DPhF1)Cl
and Ru2(DmAniF)3(DPhF2)Cl react with trimethyl-
silylacetylene under Sonogashira conditions, followed by
desilylation with K2CO3 in THF/CH3OH, to yield Ru2-
(DmAniF)3(DPhF3)Cl (1b; DPhF3 ) N-phenyl-N′-(4-
ethynylphenyl)formamidinate) and Ru2(DmAniF)3-
(DPhF4)Cl (1c; DPhF4 ) N,N′-di(4-ethynylphenyl)-
formamidinate), respectively (Supporting Information).
As shown in Table 1, both the mono(ethyne) compound
1b and bis(ethyne) compound 1c undergo click reactions
with PhCH2N3 to furnish compounds 2b,c, respectively.
Further alkynylation of compounds 2b with 10 equiv
of LiC4TMS resulted in a mixture of mono(butadiynyl)
(3b) and bis(butadiynyl) axial adducts (4b) that were
separated via column chromatography. Compounds 3c
and 4c were prepared from 2c under similar conditions.
(11) Xu, G.-L.; Ren, T. Inorg. Chem. 2001, 40, 2925.

2566 Organometallics, Vol. 24, No. 11, 2005
Table 1. Ru2-Containing Ethynes and Their Click Products
Communications
a Conditions for 2: CuSO4‚5H2O (5 mol %), sodium ascorbate (10 mol %), PhCH2N3, ButOH/H2O (2:1, v/v). Yields: 86% for 2b and 77%
for 2c. b Conditions for 3 and 4: LiC4TMS (10 equiv), THF; Yields: 52% for 3b and 34% for 4b. Yields: 43% for 3c and 28% for 4c.
click methodology reported herein to both the synthesis
of Ru2-containing bioconjugates and surface modifica-
tion is currently under way. It is noteworthy that the
DArF type ligands have played a critical role in both
the supramolecular assemblies and DNA-binding agents
based on metal-metal-bonded dinuclear compounds.12
Hence, the Cu(I)-catalyzed azide alkyne reaction based
on both DPhF3 and DPhF4 ligands may add a new
dimension to the research of metal-metal bonded
dinuclear compounds.
Figure 3. Cyclic voltammograms of compound 4c and Ru2-
Acknowledgment. We thank the National Science
Foundation (Grant No. CHE0242623) for financial sup-
port and Mr. W.-Z. Chen for providing compound 1a.
(DmAniF)4(C4SiMe3)2 recorded in 0.20 M THF solution of
Bu4NPF6 at a scan rate of 0.10 V/s.
Supporting Information Available: Text, figures, and
a table giving details of synthesis and characterizations of
compounds 1-4 and X-ray crystallographic data as CIF files
for compounds 4a and 3c. This material is available free of
charge via the Internet at http://pubs.acs.org.
We have demonstrated that the Cu(I)-catalyzed azide
alkyne reaction can be applied to inorganic and orga-
nometallic species through the use of ligands bearing
peripheral ethyne groups. This click reaction occurs
quantitatively in situ, which is essential for the forma-
tion of bioconjugates, and yields of purified click prod-
ucts were satisfactory as well (63-86%). Most signifi-
cantly, the formation of 1,2,3-triazole on the periphery
of Ru2 metallaynes has almost no effect on both the
coordination geometry around the Ru2 core and elec-
tronic properties of Ru2 metallaynes. Extension of the
OM0501632
(12) (a) Cotton, F. A.; Walton, R. A. Multiple Bonds between Metal
Atoms; Oxford University Press: Oxford, U.K., 1993. (b) Cotton, F.
A.; Lin, C.; Murillo, C. A. Acc. Chem. Res. 2001, 34, 759. (c) Cotton, F.
A.; Lin, C.; Murillo, C. A. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 4810.
(d) Chisholm, M. H. Dalton 2003, 3821. (e) Chifotides, H. T.; Dunbar,
K. R. Acc. Chem. Res. 2005, 38, 14.