Synthesis of a metal-free coordinating ring via formation of a cleavable [2]catenane

Article abstract of DOI:10.1039/c3cc46452k

We describe an efficient methodology which allows for the preparation of a macrocycle incorporating a free coordination site. It is based on a transition metal-templated strategy and RCM to provide access to a Cu(i)-complexed [2]catenane consisting of the desired cyclised compound and a cleavable ring. Release of the cleavable ring leads to the formation of the target macrocycle in quantitative yield. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3cc46452k

ChemComm
View Article Online
View Journal
COMMUNICATION
Synthesis of a metal-free coordinating ring via
formation of a cleavable [2]catenane†
Cite this: DOI: 10.1039/c3cc46452k
´ ´
Frederic Niess and Jean-Pierre Sauvage*
Received 23rd August 2013,
Accepted 26th September 2013
DOI: 10.1039/c3cc46452k
www.rsc.org/chemcomm
We describe an efficient methodology which allows for the pre-
paration of a macrocycle incorporating a free coordination site. It is
based on a transition metal-templated strategy and RCM to pro-
vide access to a Cu(I)-complexed [2]catenane consisting of the
desired cyclised compound and a cleavable ring. Release of the
cleavable ring leads to the formation of the target macrocycle in
quantitative yield.
Scheme 1 Synthesis of macrocycle 2 (i) Grubbs’ 1st-gen. Catalyst, CH2Cl2, r.t.,
5 d, 72%.
The development of efficient synthetic strategies using transition
metal complexes to obtain macrocyclic species has undergone
spectacular progress1 due to the importance of these compounds considered based on chelating group protection by coordina-
in various fields such as models of transition metal-containing tion to a metal centre as depicted in Scheme 2. In the presence
enzymes in bioinorganic chemistry,2 chemical topology,3 mole- of copper(I),9 a complex between the precursor of the desired
cular machines4 or supramolecular chemistry in general.5 The macrocycle and another ring, whose particular feature is its
ring-closing metathesis (RCM) methodology applied to the syn- cleavable nature, is expected to afford a Cu(I)-complexed pseudo-
thesis of transition metal-complexed large rings turned out to [2]rotaxane.10 Formation of the threaded species is mostly to
be particularly efficient.6
protect the coordination site and thus to inhibit any possible
In previous work performed in collaboration with Grubbs interaction between the catalyst and the chelate. Subsequently,
and his co-workers, phenanthroline-based macrocycles and the cyclization reaction using RCM should lead to a Cu(I)-
[2]catenanes were prepared by intramolecular RCM.7 One of complexed [2]catenane. In a final step, demetalation and cleavage
the key building blocks was the acyclic ligand 2, composed of a of the ancillary ring will afford the desired macrocycle. It should
2,9-diphenyl-1,10-phenanthroline symmetrically substituted with be stressed that the use of a macrocycle such as 3 as a protective
ethylene oxide groups terminated by olefins. Surprisingly, the group is important. Replacing the ring by an acyclic chelating
direct intermolecular RCM of the free ligand 2 proceeded with group L would lead to scrambling of the ligands around the
lower yield (72%)8 (depicted in Scheme 1) than that leading to the copper(I) centre, leading to the thermodynamic mixture consist-
interlocked system and involving two cyclisation reactions (92%). ing of two symmetrical complexes, namely [CuL2]+ and [Cu(2)2]+,
One of the reasons for explaining this unexpected result is that in addition to the desired asymmetric complex containing two
the compatibility between Grubbs strategy and the chelating different ligands, [CuL(2)]+. A catenane consisting of two non
groups is only limited, the presence of coordinating fragments cleavable rings would thus be obtained from [Cu(2)2]+ in a
in the molecular components to be cyclised being detrimental significant proportion. The beauty of the ‘‘cyclic approach’’ is
to the use of Ru-based catalysts.
that the threaded species is the thermodynamic well.
In order to improve the synthesis of macrocycles incorpor-
In order to achieve the synthesis of macrocycle 1 (see Scheme 4)
ating free coordination sites, a new synthetic strategy was using the strategy depicted in Scheme 2, the 31-membered
macrocycle 3, previously used by our group,11 was chosen. This
macrocycle incorporates a lactone function, which should
´
´
Institut de Science et d’Ingenierie Supramoleculaires (ISIS),
survive the conditions of copper(I)-templated catenane forma-
tion and allow cleavage of the macrocycle and liberation of the
target ring under mild conditions at the end of the synthetic
pathway.
´
´
Universite de Strasbourg et CNRS, 8 allee Gaspard Monge, 67000 Strasbourg,
France. E-mail: jpsauvage@unistra.fr
† Electronic supplementary information (ESI) available: Synthetic procedures and
characterization of products. See DOI: 10.1039/c3cc46452k
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun.

View Article Online
Communication
ChemComm
1
at 7.18 and 8.45 ppm in the H NMR spectrum of precursor 2
shifted to 6.19–5.99 and 7.60–7.33 ppm, respectively, in that of
4+ (Scheme 5a and b).
Compound 4+ was then converted to Cu(I)-[2]catenane 5+ by
olefin metathesis. Grubbs’ first generation catalyst (0.05 eq.) was
added and the mixture was stirred for 6 h at room temperature.
Cu(I)-complexed [2]catenane 5+ was obtained in 98% yield after
purification by SiO2 chromatography. This RCM reaction was
very effective compared to the direct cyclization of compound 1
(see Scheme 1). The reaction was significantly faster (6 hours
for 4+ to 5+ versus 5 days for 2 to 1) and the yield was better (98%
compared to 72% for the RCM reaction of 4+ and 2 respectively).
The efficiency of the RCM reaction yielding 5+ resulted from
efficient protection of the chelating group by copper(I) and
possibly the preorganization of the olefinic terminal units due
to the electronic interactions between the oxygen atoms and the
copper-complexed 1,10-phenanthroline nuclei.13 The two terminal
olefinic signals (h, i) observed at 5.99–5.87 and 5.36–5.15 ppm in
Scheme 2 Schematic representation of the synthetic strategy: (a) synthesis of a
copper-complexed pseudo[2]rotaxane from cleavable ring, copper(I) and open-
chain macrocycle precursor;8 (b) cyclization step and formation of a copper-
complexed [2]catenane;8 (c) demetallation of the [2]catenane; (d) release of the
cleavable ring leading to the desired macrocycle. Note that the copper(I) centers
are represented by brown disks. The blue parts are the coordinating groups
incorporated in the macrocycle or the cyclization precursor. The olefinic terminal
units are represented by red dots and the double bond formed is represented
by orange disks. The open-chain fragment used in the threading reaction is
indicated in black.
1
the H NMR spectrum of the Cu(I)-complexed pseudo[2]rotaxane
4+ disappeared and only one broad signal at 5.88–5.79 ppm
corresponding to the 4 alkene protons (h) was detected for 5+
(Scheme 5b and c).
In analogy to literature procedures,9 demetalation of catenane
5+ with potassium cyanide in a mixture of dichloromethane,
acetonitrile and water afforded [2]catenand 6 in 100% yield.
[2]Catenand 6 was characterized by 1H NMR spectroscopy
(1D, COSY) (Scheme 5d) as well as high resolution electrospray
mass spectroscopy (HRES-MS).
Scheme 3 Cleavable 31-membered macrocycle
3 incorporating a lactone
function.
Subsequently, the macrocyclic lactone 3, component of catenane
The synthesis of macrocycle 1 using the strategy shown in 6, was cleaved and the resulting acyclic fragment spontaneously
Scheme 2 is depicted in Scheme 4. The Cu(I)-complexed unthreaded from the interlocked structure. For this purpose a slight
pseudo[2]rotaxane 4+ was obtained instantly and quantitatively by excess of KOH in MeOH (0.1 M) was added to a solution of
the reaction of 3 with a stoichiometric amount of Cu(CH3CN)4PF6 [2]catenand 6 in THF–MeOH and stirred for 1 hour at room
in a dichloromethane–acetonitrile mixture followed by addition temperature. After separation of the saponification product obtained
of the macrocycle precursor 2. Quantitative formation of 4+ was as an insoluble solid, the filtrate was pumped off to afford quantita-
evidenced by 1H NMR spectroscopy since specific aromatic tively macrocycle 1. Macrocycle 1 was characterized by 1H NMR
proton resonances were shifted upon formation of the threaded spectroscopy (1D, COSY) (Scheme 5e), 13C NMR spectroscopy and
species.12 For example, meta and ortho (m, o) protons observed high-resolution electrospray mass spectroscopy (HRES-MS).
Scheme 4 Synthesis of compound 7: (i) macrocycle 3, Cu(CH3CN)4PF6, CH2Cl2/CH3CN, r.t., 10 min, 100%; (ii) Grubbs’ 1st-gen. Catalyst, CH2Cl2, r.t., 6 h, 98%; (iii) KCN,
CH2Cl2/CH3CN/H2O, r.t., 30 min, 100%; (iv) KOH, CH2Cl2/MeOH, r.t., 1 h, 100%; Pd/C, THF, r.t., 12 h, 92%.
c
Chem. Commun.
This journal is The Royal Society of Chemistry 2013

View Article Online
ChemComm
Communication
3 (a) R. S. Forgan, J.-P. Sauvage and J. F. Stoddart, Chem. Rev., 2011,
111, 5434; (b) J. D. Megiatto Jr. and D. I. Schuster, J. Am. Chem. Soc.,
2008, 130, 12872; (c) Y. Sato, R. Yamasaki and S. Saito, Angew. Chem.,
Int. Ed., 2009, 48, 504; (d) D. A. Leigh, P. J. Lusby, S. J. Teat, A. J.
Wilson and J. K. Y. Wong, Angew. Chem., Int. Ed., 2001, 40, 1538;
(e) L. Hogg, D. A. Leigh, P. J. Lusby, A. Morelli, S. Parsons and J. K. Y.
Wong, Angew. Chem., Int. Ed., 2004, 43, 1218; ( f ) H. Adams,
E. Ashworth, G. A. Breault, J. Guo, C. A. Hunter and P. C. Mayers,
Nature, 2001, 411, 763.
4 (a) E. Beves, B. A. Blight, C. J. Campbell, D. A. Leigh and R. T.
McBurney, Angew. Chem., Int. Ed., 2011, 50, 9260; (b) E. R. Kay,
D. A. Leigh and F. Zerbetto, Angew. Chem., Int. Ed., 2007, 46, 72;
(c) N. H. Evans, C. J. Serpell and P. D. Beer, Chem.–Eur. J., 2011,
17, 7734.
5 J.-M. Lehn, Supramolecular chemistry concepts and perspectives, VCH,
1995.
6 (a) A. V. Chuchuryukin, H. P. Dijkstra, B. M. J. M. Suijkerbuijk,
R. J. M. Klein Gebbink, G. P. M. van Klink, A. M. Mills, A. L. Spek and
G. van Koten, Angew. Chem., Int. Ed., 2003, 42, 228; (b) E. C.
Scheme 5 Partial 1H NMR spectra in CD2Cl2 of (a) compound 2; (b) Cu(I)-complexed
pseudo[2]rotaxane 4+; (c) Cu(I)-[2]catenane 5+; (d) [2]catenand 6; (e) macrocycle 1;
(f) macrocycle 7. Atom numbering is indicated in Schemes 1 and 3.
¨
Constable, C. E. Housecroft, M. Neuburger, P. J. Rosel, S. Schaffner
and J. A. Zampese, Chem.–Eur. J., 2009, 15, 11746; (c) C. O. Dietrich-
Buchecker, G. Rapenne and J.-P. Sauvage, Chem. Commun., 1997, 2053;
(d) J. Guo1, P. C. Mayers, G. A. Breault and C. A. Hunter, Nat. Chem.,
2010, 2, 218.
7 (a) B. Mohr, M. Weck, J.-P. Sauvage and R. H. Grubbs, Angew. Chem.,
Int. Ed. Engl., 1997, 36, 1308; (b) M. Weck, B. Mohr, J.-P. Sauvage and
R. H. Grubbs, J. Org. Chem., 1999, 64, 5463.
8 As a control experiment, the RCM reaction from 2 to 1 was
performed again and the same yield as the one reported in
ref. 7 was obtained. All the experiment details are provided in the
ESI†.
9 (a) C. O. Dietrich-Buchecker, J.-P. Sauvage and J.-M. Kern, J. Am.
Chem. Soc., 1984, 106, 3043; (b) M.-C. Jimenez, C. Dietrich-Buchecker
and J.-P. Sauvage, Angew. Chem., Int. Ed., 2000, 39, 3284;
(c) B. Champin, P. Mobian and J.-P. Sauvage, Chem. Soc. Rev., 2007,
36, 358.
Selective hydrogenation of the double bound of macrocycle
1 was carried out using Pd/C in an H2 atmosphere. The hydro-
genated macrocycle 7 was obtained in 92% yield. The two
1
alkene protons (h) observed at 5.87–5.81 ppm in the H NMR
spectrum of macrocycle 1 disappeared and a broad signal at
1.80–1.60 ppm corresponding to the hydrogenated double bond
(h) was detected for macrocycle 6 (Scheme 5f).
To conclude, an efficient synthesis of metal-free macrocycles
through intermolecular RCM was presented. The strategy is
based on chelating group protection which inhibited interference
between the coordinating group and the ruthenium-based
catalyst thus favouring the cyclisation reaction. This synthesis
principle could easily be generalized to many other systems and
thus facilitate the preparation of coordinating rings incorpor-
ating various groups (nitrogen based chelates or phosphines,14
for example).
10 C. O. Dietrich-Buchecker, J.-P. Sauvage and J.-P. Kintzinger,
Tetrahedron Lett., 1983, 24, 5095.
11 This strategy was already envisaged several years ago for a different
project but was never published. For further details, see: (a) Y. Matter,
´
`
´
J.-M. Kern and J.-P. Sauvage, Elaboration d’une strategie de synthese
ˆ
´
iterative de chaınes polymeriques unidimentionnelles constituees
´
´
d’anneaux entrelaces, Master thesis, Universite Louis Pasteur,
Strasbourg, 1992; (b) A. Joosten, Y. Trolez, V. Heitz and J.-P.
Sauvage, Chem.–Eur. J., 2013, 19, 12815.
We wish to thank the Centre International de Recherche aux
12 (a) A. Livoreil, J.-P. Sauvage, N. Armaroli, V. Balzani, L. Flamigni and
`
Frontieres de la Chimie of Strasbourg and the CNRS for
´
B. Ventura, J. Am. Chem. Soc., 1997, 119, 12114; (b) D. J. Cardenas,
˜
financial support.
P. Gavina and J.-P. Sauvage, J. Am. Chem. Soc., 1997, 119, 2656;
(c) C. O. Dietrich-Buchecker and J.-P. Sauvage, Tetrahedron, 1990, 46, 503;
(d) J.-F. Nierengarten, C. O. Dietrich-Buchecker and J.-P. Sauvage, J. Am.
Chem. Soc., 1994, 116, 375.
Notes and references
1 (a) N. V. Gerbeleu, V. B. Arion and J. Burgess, Template synthesis of 13 M. Cesario, C. O. Dietrich-Buchecker, J. Guilhem, C. Pascard and
¨
macrocyclic compounds, VCH, 1999; (b) C. A. Schalley, F. Vogtle and
J. P. Sauvage, J. Chem. Soc., Chem. Commun., 1985, 244.
K. H. Dotz, Top. Curr. Chem., 2005, 249, 1; (c) K. Bowman-James, 14 (a) M. Mohankumar, M. Holler, J.-F. Nierengarten and J.-P. Sauvage,
¨
Encyclopedia of Inorganic and Bioinorganic Chemistry, VCH, 2011.
2 J.-N. Rebilly and O. Reinaud, Supramol. Chem.: Mol. Nanomater.,
2012, 4, 1771.
Chem.–Eur. J., 2012, 18, 12192; (b) M. Mohankumar, M. Holler,
M. Schmitt, J.-P. Sauvage and J.-F. Nierengarten, Chem. Commun.,
2013, 49, 1261.
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun.