Functionalized Metalated Cavitands via Imidation and Late-Stage Elaboration

Article abstract of DOI:10.1002/ejoc.201500714

Efficient methods for the preparation of functionalized metallated cavitands are described. Functional groups can be either introduced by an imidation of metal-oxo complexes or by a late-stage elaboration of the imido ligands. By using diversified iminoph

Full text of DOI:10.1002/ejoc.201500714

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201500714
Functionalized Metalated Cavitands via Imidation and Late-Stage Elaboration
Yanchuan Zhao[a] and Timothy M. Swager*[a]
Keywords: Calixarenes / Cavitands / Late-stage functionalization / Supramolecular chemistry
Efficient methods for the preparation of functionalized
metallated cavitands are described. Functional groups can
be either introduced by an imidation of metal-oxo complexes
or by a late-stage elaboration of the imido ligands. By using
diversified iminophosphorane (PPh3=NR) reagents, π-conju-
bornene moieties were successfully introduced. Furthermore,
the iodo and alkynyl groups on the imido ligands are capable
of undergoing efficient Sonogashira cross-coupling and
copper-catalyzed azide alkyne cycloaddition reactions,
thereby providing facile access to complex architectures con-
gated pyrene, redox active ferrocene, and polymerizable nor- taining metallated cavitands.
tands.[1a,1d,6] Among the metalated cavitands, tungsten(VI)
Introduction
calix[4]arene complexes have displayed considerable utility
as a result of their stability and established coordination
chemistry.[7] Although some tungsten calixarene complexes
were synthesized and characterized, the method to intro-
duce these scaffolds to other platforms with various func-
tions are limited. The examples of these compounds have
largely leveraged established calixarene chemistries that fo-
cus on transformations of phenol groups on the lower rim
(Scheme 1, a) or electrophilic reaction para to the oxygen
groups.[8] Although these methods can be used to create
ligating groups to assemble metalated cavitands, greater di-
versity is possible by adding functionality independent of
the calixarene group. To this end we have targeted direct
transformations of tungsten–oxo calixarene complexes as a
result of their facile preparation and inherent stability. We
envisioned that various imido ligands could be directly in-
troduced through imidation reactions and further elabora-
Metalated cavitands with endohedral ligand affinity are
of interest as a result of their selectivity provided by the
precise shape of the cavity.[1] In comparison to related
macrocyclic compounds such as calixarenes, resorcinarenes
or cyclodextrins, metalated cavitands often possess en-
hanced binding capabilities that allow for selective molec-
ular recognition in solution.[1,2] These receptors make use
of strong directional metal–ligand interaction and hence
metalated cavitands are appealing candidates for directed
self-assembly and chemosensing.[1b] In addition, these sys-
tems can be considered as metalloenzyme mimics and can
display unique catalytic reactivity as a result of the confined
environment defined by the cavity.[3,4] Given these striking
characteristics, methods to functionalize metalated cavit-
ands that are adaptable to construct complex architectures
are likely to find utility. Direct late-stage functionalization
of metalated cavitands mitigates the synthetic uncertainties
in preparing complex ligands. However, this approach is ra-
rely explored as a consequence of the lability of metalated
cavitands and difficulties of their isolation from complex
mixtures. Herein, we report a strategy to access a diversity
of functionalized metalated cavitands through the forma-
tion of metal–imido complexes and subsequent elabora-
tions.
Calixarenes are an important class of macrocyclic com-
pounds with numerous applications in sensing and supra-
molecular chemistry.[5] The multiple phenol groups of this
scaffold are capable of chelating early transition metals, and
hence calixarenes are supporting ligands for metalated cavi-
[a] Department of Chemistry
Massachusetts Institute of Technology
Cambridge, Massachusetts 02139, USA
E-mail: tswager@mit.edu
https://swagergroup.mit.edu/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500714.
Scheme 1. Functionalized calixarenes and metalated cavitands.
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Y. Zhao, T. M. Swager
SHORT COMMUNICATION
tion of the imido ligands can produce complex functional
architectures (Scheme 1, b).
Results and Discussion
Tungsten calixarene imido complexes were previously
prepared from air-sensitive WVI(=NR)2Cl2 or a calixarene
tungsten(IV) olefin adduct, both of which are not readily
accessible.[9] We recently found that simple imido ligands
can be incorporated by a direct imidation of the tungsten–
oxo calixarene complexes by using iminophosphorane
reagents.[7c] A diversity of these reagents were directly
prepared from the corresponding anilines using PPh3/
iPr2EtN/C2Cl6 (Scheme 2, a) or by reacting arylazides with
triphenylphosphine (Scheme 2, b).[10] We found that the two
ortho-methyl groups on the arylimido ligand are crucial to
the success of the transformation, and therefore, various
functionalities were installed on the para-position of the an-
iline. In addition to enhancing the stability of the corre-
sponding tungsten–imido complex, methyl groups are pro-
posed to impart sufficient nucleophilicity to the imino-
phosphorane.[11,12] It is noteworthy that the two methods in
Scheme 2 are complimentary. For instance, anilines 1a–1d
have low solubility in acetonitrile and the conversion to
arylazides is low, whereas the alkynyl group of 1h is not
compatible with the reaction conditions of method (a). To
examine the scope of this method, we selected a series of
functional groups that are relevant to various applications.
For example, long alkyl chains and pyrene moieties are
known to display favorable interactions with carbon-based
nanomaterials, such as carbon nanotubes and graphene (2a
and 2b).[13] Attachment of redox active ferrocene moieties
creates electrochemically responsive materials (2c and
2d).[14] A polymerizable norbornene moiety was examined
with the aim to produce polymers appended with metalated
cavitands (2e). Additionally, to explore the possible elabora-
tion of the metal cavitands at a late-stage, synthetic handles,
such as iodo- and alkynyl groups were installed on the
imido ligands (2f–g).
Scheme 2. Preparation of functionalized iminophosphorane rea-
gents.
With iminophosphorane reagents in hand, we end-
eavored to prepare functionalized tungsten cavitands. The
tungsten-oxo calixarene complex was chosen as a substrate
and is readily prepared in situ from tBu-calixarene and
WOCl4. The subsequent addition of various iminophos-
phorane reagents (2a–2h) in refluxing toluene afforded the
corresponding tungsten–imido cavitands. As shown in
Scheme 3, the tungsten–imido cavitands were produced in
good to excellent yields (70–84%) by this one-pot pro-
cedure. Functional groups, such as alkene (4e), alkynyl (4h),
halide (4f, 4g), and ferrocene (4c, 4d) were tolerated under
Scheme 3. Preparation of functionalized tungsten cavitands
through imidation.
Bimetallic metal cavitands are appealing building-block
the reaction conditions, thereby providing access to highly candidates for constructing self-assembling supramolecular
diversified metal cavitands. It is noteworthy that the tung- polymers. A molybdenum dinuclear cavitand had been pre-
sten cavitands are stable to column chromatography using viously reported, its preparation required the use of a di-
silica gel and the byproduct triphenylphosphine oxide is molybdenum complex precursor.[16] To enable facile access
easily separated from the cavitand products. The structures to dinuclear metalated cavitands, we first prepared imino-
of 4a, 4c, and 4d were unambiguously confirmed by X-ray phosphoranes 2i and 2g using method (b) as shown in
crystallography (Figure 1).[15]
Scheme 2, and tested their performance in accessing di-
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Functionalized Metalated Cavitands
Figure 1. X-ray crystal structures of tungsten cavitands.
nuclear cavitands. Although the reaction was sluggish in re-
fluxing toluene at 125 °C, we found that the use of a higher
refluxing temperature (155 °C) afforded good yields of di-
nuclear tungsten cavitands. Both of the linear and the bent
cavitands were prepared using this method. It should be
mentioned that isolated tungsten–oxo complex (5) was em-
ployed in this reaction to enable a precise control of the
reactant ratio. The X-ray crystal structure confirmed the
linear geometry of 4i (Scheme 4).[15] The well-defined coor-
dination chemistry and predictable geometry makes these
dinuclear cavitands interesting building blocks to construct
supramolecular assemblies with ligands that can fit into the
cavitand and coordinate to the tungsten center. We have
attempted the construction of supramolecular assembly by
mixing 4i with N,NЈ-(dodecane-1,12-diyl)diformamide. The
formation of assembly in both solution and solid state was
confirmed by nuclear magnetic resonance (NMR) and in-
frared (IR) spectroscopy (Figure S1–S5 in the Supporting
Information).
Scheme 4. Preparation of dinuclear tungsten cavitands and X-ray
crystal structure of 4i:2CH3CN.
We next examined the feasibility of direct elaboration of
the tungsten–imido cavitands. Although these cavitands are
thermally stable, they tend to decompose under highly basic
or acidic conditions, which poses synthetic challenges for
further transformations. We envisioned that the transition-
metal-catalyzed reactions employing mild reaction condi-
tions might be compatible with these metal cavitands.[17]
However, our initial attempts with palladium-catalyzed
Suzuki and Stille coupling reactions failed.[18] Interestingly,
Sonogashira coupling using an organic base was very ef-
ficient[19] and we also found the copper-catalyzed azide alk-
yne cycloaddition (also known as the click reaction) pro-
ceeded smoothly in aqueous solution (Scheme 5).[20] Given
the wide applications of these coupling reactions in syn-
thetic chemistry and material science, these late-stage elabo-
rations will allow facile incorporation of metalated cavit-
ands into a variety of platforms.
Scheme 5. Late-stage elaboration of tungsten–imido cavitands.
the first example of a metalated calixarene cavitand with a
Considering the availability of diverse methods to modify substituent on the methylene bridge. The pyrene-function-
calixarenes, diversified architectures could be constructed alized calixarene was also prepared for potential use as a
by replacing one of the methylene bridges or by upper-rim molecular tweezer.[22] As illustrated in Scheme 6, these
functionalization of aromatic rings. To this end, we have modified calixarenes were smoothly transformed to the cor-
introduced a long alkyl group at the meso position of responding tungsten cavitands under our reaction condi-
calixarene,[21] and the corresponding product 4m represents tions.
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Y. Zhao, T. M. Swager
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Chem. Soc. Rev. 2015, 44, 449–466; c) N. Li, R. G. Harrison,
J. D. Lamb, J. Inclusion Phenom. Macrocyclic Chem. 2014, 78,
39–60; d) G. Chen, M. Jiang, Chem. Soc. Rev. 2011, 40, 2254–
2266; e) E. B. Brouwer, G. D. Enright, C. I. Ratcliffe, G. A. Fa-
cey, J. A. Ripmeester, J. Phys. Chem. B 1999, 103, 10604–10616;
f) E. M. M. Del Valle, Process Biochem. 2004, 39, 1033–1046.
a) Y. Rondelez, A. Duprat, O. Reinaud, J. Am. Chem. Soc.
2002, 124, 1334–1340; b) J.-N. Rebilly, B. Colasson, O. Bistri,
D. Over, O. Reinaud, Chem. Soc. Rev. 2015, 44, 467–489; c) D.
Over, X. Zeng, C. Bornholdt, J. Marrot, O. Reinaud, Inorg.
Chem. 2013, 52, 14089–14095; d) N. Le Poul, B. Douziech, J.
Zeitouny, G. Thiabaud, H. Colas, F. Conan, N. Cosquer, I.
Jabin, C. Lagrost, P. Hapiot, O. Reinaud, Y. Le Mest, J. Am.
Chem. Soc. 2009, 131, 17800–17807; e) J.-G. Liu, Y. Naruta, F.
Tani, Chem. Eur. J. 2007, 13, 6365–6378; f) J. Gout, A.
Visˇnjevac, S. Rat, A. Parrot, A. Hessani, O. Bistri, N. Le Poul,
Y. Le Mest, O. Reinaud, Inorg. Chem. 2014, 53, 6224–6234; g)
J.-N. Rebilly, O. Reinaud, Supramol. Chem. 2014, 26, 454–479.
a) D. M. Homden, C. Redshaw, Chem. Rev. 2008, 108, 5086–
5130; b) G. Arnott, H. Heaney, R. Hunter, P. C. B. Page, Eur.
J. Org. Chem. 2004, 5126–5134; c) R. Gramage-Doria, D. Arm-
spach, D. Matt, L. Toupet, Chem. Eur. J. 2012, 18, 10813–
10816; d) S. H. A. M. Leenders, R. Gramage-Doria, B.
de Bruin, J. N. H. Reek, Chem. Soc. Rev. 2015, 44, 433–448; e)
D. Armspach, D. Matt, F. Peruch, P. Lutz, Eur. J. Inorg. Chem.
2003, 805–809.
[3]
[4]
[5]
Scheme 6. Preparation of functionalized tungsten cavitands.
a) D.-S. Guo, V. D. Uzunova, X. Su, Y. Liu, W. M. Nau, Chem.
Sci. 2011, 2, 1722–1734; b) Diamond, M. A. McKervey, Chem.
Soc. Rev. 1996, 25, 15–24; c) M. Yilmaz, S. Erdemir, Turk. J.
Chem. 2013, 37, 558–585; d) S. B. Nimse, T. Kim, Chem. Soc.
Rev. 2013, 42, 366–386; e) D.-S. Guo, Y. Liu, Chem. Soc. Rev.
2012, 41, 5907–5921.
Conclusions
In summary, we have developed an efficient strategy to
access functionalized metalated cavitands. The functional
groups could be introduced either by a direct imidation of
a tungsten–oxo calixarene complex by using various imino-
phosphorane reagents or by a late-stage elaboration of the
imido ligands of the metalated cavitands. Various moieties,
such as π-conjugated pyrene, redox active ferrocene, and
polymerizable norbornene were successfully incorporated,
demonstrating the broad applicability of the current
method. Furthermore, the late-stage elaboration of tung-
sten cavitands by Sonogashira reaction and copper-
catalyzed azide alkyne cycloaddition reaction opens up
opportunities for introducing these highly selective endo-
hedral Lewis acidic receptors into various existing plat-
forms. We expect the current strategy will promote the ex-
ploitation of new functional materials based on metalated
cavitands.
[6]
[7]
C. Wieser, C. B. Dieleman, D. Matt, Coord. Chem. Rev. 1997,
165, 93–161.
a) A. Vigalok, T. M. Swager, Adv. Mater. 2002, 14, 368–371; b)
A. Vigalok, Z. Zhu, T. M. Swager, J. Am. Chem. Soc. 2001,
123, 7917–7918; c) Y. Zhao, T. M. Swager, J. Am. Chem. Soc.
2013, 135, 18770–18773; d) Y. Zhao, G. Markopoulos, T. M.
Swager, J. Am. Chem. Soc. 2014, 136, 10683–10690; e) B. Xu,
T. M. Swager, J. Am. Chem. Soc. 1993, 115, 1159–1160; f) F.
Corazza, C. Floriani, A. Chiesi-Villa, C. Rizzoli, Inorg. Chem.
1991, 30, 4465–4468; g) A. Arduini, C. Massera, A. Pochini,
A. Secchi, F. Ugozzoli, New J. Chem. 2006, 30, 952–958; h) P.
Mongrain, J. Douville, J. Gagnon, M. Drouin, A. Decken, D.
Fortin, P. D. Harvey, Can. J. Chem. 2004, 82, 1452–1461; i) B.
Xu, T. M. Swager, Angew. Chem. Int. Ed. Engl. 1996, 35, 2094–
2097; Angew. Chem. 1996, 108, 2238.
a) W. Sliwa, M. Deska, ARKIVOC (Gainesville, FL, U.S.)
2011, 496–551; b) V. K. Jain, P. H. Kanaiya, Russ. Chem. Rev.
2011, 80, 75–102.
a) U. Radius, J. Attner, Eur. J. Inorg. Chem. 1999, 2221–2231;
b) G. Guillemot, E. Solari, C. Floriani, C. Rizzoli, Organome-
tallics 2001, 20, 607–615.
[8]
Supporting Information (see footnote on the first page of this arti-
cle): Full experimental procedures, characterization data and 1H
and 13C NMR spectra.
[9]
[10]
[11]
a) F. Zeng, H. Alper, Org. Lett. 2010, 12, 1188–1191; b) K.
Barral, A. D. Moorhouse, J. E. Moses, Org. Lett. 2007, 9,
1809–1811; c) P. M. Fresneda, P. Molina, Synlett 2004, 1–17.
Tungsten calixarene phenylimido complex is known to be in
equilibrium between monomer and dimer in solution. See ref
9b.
J. C. Axtell, R. R. Schrock, P. Müller, S. J. Smith, A. H. Hov-
eyda, Organometallics 2014, 33, 5342–5348.
a) Y.-L. Zhao, J. F. Stoddart, Acc. Chem. Res. 2009, 42, 1161–
1171; b) R. J. Chen, Y. Zhang, D. Wang, H. Dai, J. Am. Chem.
Soc. 2001, 123, 3838–3839.
a) R. Sun, L. Wang, H. Yu, Z.-u. Abdin, Y. Chen, J. Huang,
R. Tong, Organometallics 2014, 33, 4560–4573; b) F. Szillat,
B. V. K. J. Schmidt, A. Hubert, C. Barner-Kowollik, H. Ritter,
Macromol. Rapid Commun. 2014, 35, 1293–1300; c) W.-Y.
Wang, N.-N. Ma, S.-L. Sun, Y.-Q. Qiu, Organometallics 2014,
33, 3341–3352.
Acknowledgments
This work was supported by a National Institutes of Health
(NIGMS) grant GM095843. Y. Z. acknowledges Shanghai Institute
of Organic Chemistry (SIOC), Zhejiang Medicine and Pharmaron
for a joint postdoctoral fellowship. The authors thank Dr. Peter
Müller for collecting and solving X-ray crystal structure data.
[12]
[13]
[1] a) R. Gramage-Doria, D. Armspach, D. Matt, Coord. Chem.
Rev. 2013, 257, 776–816; b) P. D. Frischmann, M. J. MacLach-
lan, Chem. Soc. Rev. 2013, 42, 871–890; c) J. T. Lenthall, J. W.
Steed, Coord. Chem. Rev. 2007, 251, 1747–1760; d) N. Kotzen,
A. Vigalok, Supramol. Chem. 2008, 20, 129–139.
[2] a) C. D. Gutsche in Calixarenes Revisited (Ed.: J. F. Stoddart),
RSC, Cambridge, 1998; b) K. Kobayashi, M. Yamanaka,
[14]
4596
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 4593–4597

Functionalized Metalated Cavitands
[15]
[19] a) R. Chinchilla, C. Nájera, Chem. Rev. 2007, 107, 874–922; b)
R. Chinchilla, C. Najera, Chem. Soc. Rev. 2011, 40, 5084–5121.
[20] a) L. Liang, D. Astruc, Coord. Chem. Rev. 2011, 255, 2933–
2945; b) V. V. Rostovtsev, L. G. Green, V. V. Fokin, K. B.
Sharpless, Angew. Chem. Int. Ed. 2002, 41, 2596–2599; Angew.
Chem. 2002, 114, 2708.
[21] P. A. Scully, T. M. Hamilton, J. L. Bennett, Org. Lett. 2001, 3,
2741–2744.
[22] a) H. M. Colquhoun, Z. Zhu, C. J. Cardin, Y. Gan, M. G. B.
Drew, J. Am. Chem. Soc. 2007, 129, 16163–16174; b) Z. Xu,
D. R. Spring, J. Yoon, Chem. Asian J. 2011, 6, 2114–2122.
Received: June 2, 2015
CCDC-1405018 (for 4a:CH3CN), -1405019 (for 4c:CH3CN),
-1405069 (for 4d:CH3CN), and -1405020 (for 4i:2CH3CN) con-
tain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
[16]
V. C. Gibson, C. Redshaw, W. Clegg, M. R. J. Elsegood, Chem.
Commun. 1998, 1969–1970.
[17] E.-i. Negishi, J. Organomet. Chem. 2002, 653, 34–40.
[18] a) N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457–2483; b)
P. Espinet, A. M. Echavarren, Angew. Chem. Int. Ed. 2004, 43,
4704–4734; Angew. Chem. 2004, 116, 4808.
Published Online: June 24, 2015
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