Synthesis of a novel ditopic ligand incorporating directly bonded 1,10-phenanthroline and 2,2′:6′,2″-terpyridine units

Article abstract of DOI:10.1016/j.tetlet.2006.03.025

The synthesis of a rigid ditopic ligand incorporating a 1,10-phenanthroline directly connected through its 3-position to the 5-position of a 2,2′:6′,2″-terpyridine is described. The synthesis is based on a series of palladium(0)-catalyzed cross-coupling reactions (Stille and Suzuki couplings) starting from 1,10-phenanthroline and bromo-substituted pyridines.

Full text of DOI:10.1016/j.tetlet.2006.03.025

Tetrahedron Letters 47 (2006) 3471–3473
Synthesis of a novel ditopic ligand incorporating directly
bonded 1,10-phenanthroline and 2,20:60,200-terpyridine units
Pablo Gavina* and Sergio Tatay
˜
Instituto de Ciencia Molecular, Universidad de Valencia, Polı´gono de la Coma s/n, 46980 Paterna (Valencia), Spain
Received 26 January 2006; revised 15 February 2006; accepted 3 March 2006
Available online 30 March 2006
Abstract—The synthesis of a rigid ditopic ligand incorporating a 1,10-phenanthroline directly connected through its 3-position to
the 5-position of a 2,20:60,200-terpyridine is described. The synthesis is based on a series of palladium(0)-catalyzed cross-coupling
reactions (Stille and Suzuki couplings) starting from 1,10-phenanthroline and bromo-substituted pyridines.
Ó 2006 Elsevier Ltd. All rights reserved.
Oligopyridine-based linear ligands incorporating several
coordination sites are fundamental building blocks in
metallosupramolecular chemistry, particularly in the
construction of molecular helicates, racks and grids1 or
transition metal-based rotaxanes, catenanes and knots.2
Among the different binding subunits, 2,20-bipyridine,
2,20:60,200-terpyridine and 1,10-phenanthroline moieties
are by far the most widely used.3 The development of
modern palladium(0) cross-coupling based methodolo-
gies for the direct C–C bond formation has made possi-
ble the design of many symmetrical oligopyridines and
oligophenanthrolines where the pyridine or phenanthro-
line units are directly bonded or connected through
different bridging ligands, like ethynyl or phenylene
spacers.4 In some cases these ligands are also functional-
ized with ending groups which can be covalently
incorporated into larger structures.5 However, unsym-
metrical ligands containing both, a terpyridine and a
phenanthroline chelate are not as common,6 and as far
as we know, a linear ditopic ligand containing a terpyri-
dine unit directly bonded to a phenanthroline moiety was
still a challenge. Such ligand would be of great interest
in the field of molecular motors, as a rigid linear frag-
ment in the construction of bistable transition metal-
based rotaxanes.2
2,20:60,200-terpyridine (terpy) tridentate ligand and a
1,10-phenanthroline (phen) bidentate moiety. The main
feature of this ligand is that the phen and terpy units
are directly connected to one another (the 3-position of
the phen to the 5-position of the terpy), without any
bridging ligand in between. Compound 1 also possesses
two different substituents at the ends of the string which
can be further functionalized.
Our synthetic approach for compound 1 relies on the
preparation of two asymmetrically substituted phen
and terpy ligands, 2 and 3 (see Fig. 1), bearing each
one a bromine atom at the appropriate position. The
final step would be a palladium(0)-catalyzed cross-
coupling reaction between one or both ligands and the
organoboron or organotin derivative from the other
one.
As one would expect, the main difficulty for the synthe-
sis of such ligands is related to their unsymmetrical nat-
ure. 3-Bromo-8-(p-anisyl)-1,10-phenanthroline (2) was
easily prepared in 50% isolated yield from 3,8-di-
bromo-1,10-phenanthroline (4)7 and 1 equiv of p-anisyl-
phenylboronic ester 5 under Suzuki cross-coupling
conditions (Pd(PPh3)4, aq Na2CO3, toluene, reflux)
(Scheme 1). Some unreacted 4 and the symmetrically
disubstituted phenanthroline were also isolated (ca.
15–20%). The synthesis of the terpy fragment 3 was
accomplished by two consecutive cross-coupling reac-
tions involving different tributylstannyl pyridine deri-
vates. It is worth mentioning that we also tried to
prepare the less toxic and environmental friendly boron
derivatives instead of the tin compounds to carry out
We would like to report herein the synthetic route lead-
ing to the first 3,5-connected phenanthroline/terpyridine
conjugate. Ligand 1 (depicted in Fig. 1) is characterized
by the presence of two different coordination sites: a
*
Corresponding author. Tel.: +34 963544421; fax: +34 963543273;
e-mail: pablo.gavina@uv.es
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.03.025

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P. Gavin˜a, S. Tatay / Tetrahedron Letters 47 (2006) 3471–3473
Figure 1. Ditopic ligand 1 and key building blocks 2 and 3.
Scheme 1. Reagents and conditions: (i) Pd(PPh3)4, Na2CO3, toluene–H2O, reflux; (ii) (1) BuLi, THF, ꢀ78 °C; (2) Bu3SnCl; (iii) Pd(PPh3)4, toluene,
reflux; (iv) (1) BuLi, toluene, ꢀ78 °C; (2) Bu3SnCl; (v) Pd(dppf)Cl2, KOAc, DMSO, 80 °C; (vi) Pd(PPh3)4, K2CO3, DMF–H2O.
cross-coupling reactions under Suzuki conditions, but
we were unsuccessful probably due to deboronation side
reactions.8
7 with 1.5 equiv of 2,6-dibromopyridine in toluene, in
the presence of Pd(PPh3)4 afforded 6-bromo-50-methyl-
2,20-bipyridine (8) in 65% yield after chromatographic
purification. Here every attempt to use the lithiation/
stannylation protocol to obtain a tin derivative of 8
was unsuccessful. However, some preliminary results
suggested the possibility of coupling 8 with the bromo-
stannyl derivative 9, taking advantage of the higher
reactivity of the bromine atom at the 6-position of the
bipyridine to overcome possible undesired homocou-
pling side reactions. 5-Bromo-2-(tributylstannyl)pyri-
dine (9) was prepared by a selective monolithiation of
2,5-dibromopyridine at the 2-position with butyllithium
The synthesis of 5-bromo-500-methyl-2,20:60,200-terpyri-
dine (3) is schematically depicted in Scheme 1. Starting
from commercially available 2-amino-5-methylpyridine,
2-bromo-5-methylpyridine (6) was synthesized by a di-
azotation/bromination sequence with bromine, HBr
and sodium nitrite. 2-Tributylstannyl-5-methylpyridine
(7) was prepared in 95% yield from 6 by Br–Li exchange
with butyllithium at ꢀ78 °C followed by stannylation
with tributyltin chloride.9 Stille-type cross-coupling of

P. Gavin˜a, S. Tatay / Tetrahedron Letters 47 (2006) 3471–3473
3473
in toluene at ꢀ78 °C,10 followed by in situ addition of
tributyltin chloride. Compound 9 could thus be isolated
in 88% yield after a short column chromatography on
alumina. Finally, reaction of 9 with the bromobipyridine
8 under Stille cross-coupling conditions (refluxing tolu-
ene in the presence of a catalytic amount of Pd(PPh3)4)
afforded the monobromo substituted terpyridine 3 in
82% yield.11
Rojo, J.; Romero-Salguero, F. J.; Uppadine, L. H.; Lehn,
J.-M. Angew. Chem., Int. Ed. 2004, 43, 3644–3662.
2. (a) Molecular Catenanes, Rotaxanes and Knots; Dietrich-
Buchecker, C., Sauvage, J.-P., Eds.; Wiley-VCH: Wein-
heim, 1999; (b) Collin, J.-P.; Dietrich-Buchecker, C.;
´
Gavina, P.; Jimenez-Molero, M. C.; Sauvage, J.-P. Acc.
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Chem. Res. 2001, 34, 477–487.
3. Schubert, U. S.; Eschbaumer, C. Angew. Chem., Int. Ed.
2002, 41, 2892–2926.
4. Some representative examples: (a) Constable, E. C.; Ward,
M. D. J. Chem. Soc., Dalton Trans. 1990, 1405–1409; (b)
At this point, we tried to obtain either a boron or tin
derivative of the precursors 2 or 3 using classical
metal–halogen exchange methodologies with very poor
results. We could finally manage to obtain a boronic
ester derivative of the terpy ligand 3 by using the palla-
dium catalyzed Miyaura cross-coupling reaction.12
Thus, 3 was reacted with bis(neopentyl glycolato)dibo-
ron in DMSO in the presence of potassium acetate
and a catalytic amount of Pd(dppf)Cl2. Pure 5-(neopent-
yl glycolatoboron)-500-methyl-2,20:60,200-terpyridine (10)
was isolated as a white solid after recrystallization from
EtOH/CH2Cl2 in 65% yield. The desired ditopic ligand 1
could be finally obtained in 67% yield by a Suzuki cross-
coupling reaction between boronic ester 10 and the
bromophenanthroline 2.13
´
Cardenas, D. J.; Sauvage, J.-P. Synlett 1996, 916–918; (c)
Ziessel, R.; Stroh, C. Tetrahedron Lett. 2004, 45, 4055–
4501; (d) Dietrich-Buchecker, C.; Colasson, B.; Jouvenot,
D.; Sauvage, J.-P. Chem. Eur. J. 2005, 11, 4374–4386; (e)
Zong, R.; Thummel, R. P. Inorg. Chem. 2005, 44, 5984–
5986; (f) Zong, R.; Wang, D.; Hammitt, R.; Thummel, R.
P. J. Org. Chem. 2006, 71, 167–175.
5. (a) Lehmann, U.; Henze, O.; Schluter, A. D. Chem. Eur. J.
¨
1999, 5, 854–859; (b) Benaglia, M.; Ponzini, F.; Woods, C.
R.; Siegel, J. S. Org. Lett. 2001, 3, 967–969.
6. (a) Gavina, P.; Sauvage, J.-P. Tetrahedron Lett. 1997, 38,
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3521–3524; (b) Belfrekh, N.; Dietrich-Buchecker, C.;
Sauvage, J.-P. Tetrahedron Lett. 2001, 42, 2779–2781; (c)
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Jimenez-Molero, M.-C.; Dietrich-Buchecker, C.; Sauvage,
J.-P. Chem. Eur. J. 2002, 8, 1456–1466; (d) Champin, B.;
Sartor, V.; Sauvage, J.-P. New J. Chem. 2006, 30, 22–25.
7. Saitoh, Y.; Koizumi, T.; Osakada, K.; Yamamoto, T.
Can. J. Chem. 1997, 75, 1336–1339.
8. For a recent synthesis of halopyridin-2-yl-boronic esters,
see: Bouillon, A.; Lancelot, J.-C.; Santos, J. S. O.; Collot,
V.; Bovy, P. R.; Rault, S. Tetrahedron 2003, 59, 10043–
10049.
9. Schubert, U. S.; Eschbaumer, C.; Hochwimmer, G.
Synthesis 1999, 779–782.
10. Wang, X.; Rabbat, P.; O’Shea, P.; Tillyer, R.; Grabowski,
E. J. J.; Reider, P. J. Tetrahedron Lett. 2000, 41, 4335–
4338.
In conclusion, the synthesis of a novel ditopic ligand in
which a phen moiety is directly bonded through its 3-po-
sition to the 5-position of a terpy unit is described. This
ligand will be used as a linear thread in the construction
of bistable metallic rotaxanes.2 In addition complexa-
tion studies of this ligand with different transition metals
are currently in progress. Particularly, we expect that the
photophysical properties of the ruthenium(II) bis-ter-
pyridine complex will be of special interest.14
11. Compound 3: 1H NMR (CDCl3, 300 MHz): d 8.73 (d,
J = 2.3 Hz, 1H), 8.55–8.50 (m, 2H), 8.47 (d, J = 8.1 Hz,
1H), 8.43 (dd, J = 7.8 and 0.9 Hz, 1H), 8.39 (dd, J = 7.8
and 0.9 Hz, 1H), 7.96 (dd, J = 8.5 and 2.3 Hz, 1H), 7.94 (s,
J = 7.8 Hz, 1H), 7.66 (dd, J = 8.1 and 1.77 Hz, 1H), 2.42
(s, 3H). HRMS (EI): calcd for C16H12N3Br 325.021, found
325.023.
Acknowledgements
This work has been supported by the Spanish Ministerio
y Ciencia (MAT2004-03849). P.G.
acknowledges the Spanish Government for a Ramon y
´
de Educacion
´
Cajal contract, and S.T. for a Ph.D. fellowship.
12. Ishimira, T.; Murata, M.; Miyaura, N. J. Org. Chem.
1995, 60, 7508–7510.
13. Ligand 1: 1H NMR (CDCl3, 300 MHz): d 9.5 (d,
J = 2.3 Hz, 1H), 9.44 (d, J = 2.3 Hz, 1H), 9.12 (d,
J = 2.0 Hz, 1H), 8.82 (d, J = 8.3 Hz, 1H), 8.59–8.43 (m,
5H), 8.37 (d, J = 2.3 Hz, 1H), 8.26 (dd, J = 8.3 and
2.4 Hz, 1H), 7.99 (t, J = 7.8 Hz, 1H), 7.92 (s, 2H), 7.74 (d,
J = 8.7 Hz, 2H), 7.70 (s, 1H), 7.10 (d, J = 8.7 Hz, 2H),
3.91 (s, 3H) 2.44 (s, 3H). HRMS(FAB): calcd for
C35H25N5O1 531.206, found 531.205.
References and notes
1. (a) Lehn, J.-M. Supramolecular Chemistry: Concepts and
Perspectives; VCH: Weinheim, 1995; (b) Comprehensive
Supramolecular Chemistry; Sauvage, J.-P., Hosseini, W.,
Eds.; Pergamon, 1996; (c) Hanan, G. S.; Arana, C. R.;
Lehn, J.-M.; Fenske, D. Angew. Chem., Int. Ed. Engl.
1995, 34, 1122–1124; (d) Schmittel, M.; Kalsani, V.; Bats,
W. J. Inorg. Chem. 2005, 44, 4115–4117; (e) Ruben, M.;
14. Bolink, H. J.; Cappelli, L.; Coronado, E.; Gavina, P.
˜
Inorg. Chem. 2005, 44, 5966–5968.