Palladium-catalyzed C-H bond functionalization of a metal-organic framework (mof): Mild, selective, and efficient

Article abstract of DOI:10.1002/chem.201101850

Mild-mannered MOFs: A selective and efficient palladium-catalyzed C-H phenylation of a UMCM-1-type metal-organic framework (MOF) under mild conditions is reported. This highly regioselective postsynthetic modification obviates the need for a pre-existing

Full text of DOI:10.1002/chem.201101850

DOI: 10.1002/chem.201101850
À
Palladium-Catalyzed C H Bond Functionalization of a Metal–Organic
Framework (MOF): Mild, Selective, and Efficient
Thomas Drçge, Andreas Notzon, Roland Frçhlich, and Frank Glorius*[a]
Dedicated to Professor David A. Evans on the occasion of his 70th birthday
Metal–organic frameworks (MOFs) are highly porous
crystalline hybrid materials with applications in gas storage
and separation, catalysis, drug delivery, and other fields.[1–6]
The key features of MOFs lie in the structural diversity and
adjustability of their framework topology based on simple
variations in the metal ions and organic ligands. However,
because the MOF formation process is based on self-organi-
zation, only certain topologies can be obtained. For a given
set of metals and linkers, the structural variability is there-
fore limited. To allow fine tuning of the properties and to
provide access to otherwise inaccessible MOFs, methods for
the postsynthetic modification (PSM)[7,8] of known MOFs
have emerged recently.[9] PSM allows the introduction of
functionalities that are not tolerated under the conditions of
MOF formation, and provides access to different topologies,
incompatible with pre-existing structural motifs. In addition,
PSM also represents an efficient and systematic approach
for the rapid generation of a family of isoreticular MOFs.[9]
However, the synthetic tools available for PSM are exceed-
ingly restricted by the sensitivity of MOFs to heat, acids,
and bases.[10] Furthermore, the small pore size and orderly
structure of MOFs severely hinder the approach of the re-
acting molecules to the active site and thus limit the re-
agents available for PSM. So far, PSM of MOFs has relied
on functional group interconversions, such as methylation of
a pyridyl group,[11] deprotonation[12] or acylation of an alco-
hol or amine,[13] reduction of an aldehyde or formation of an
imine,[14] “click” chemistry,[15] bromination of a double
bond,[16] or photochemical deprotection.[17] Although func-
tional group interconversion increases the versatility of
MOFs, the requirement for an initial functionality greatly
limits the synthetic potential of PSMs.
ally not classified as a functional group, because they are
mostly unreactive under classical reaction conditions. In the
past few years, however, transition-metal-based methods for
[18,19]
À
C H functionalization have made tremendous progress.
This chemistry seems to be optimal for the postsynthetic
modification of MOFs, since it obviates the need for a pre-
existing functional group. However, several challenges arise,
once this powerful chemistry is applied to MOF modifica-
À
tion. Although most C H functionalization methods rely on
rather forcing conditions, mild conditions[20–23] are crucial to
preserve the MOF architecture. Furthermore, high levels of
selectivity and excellent chemical yields are mandatory to
maintain the uniformity of the material.
À
A method for the selective and efficient C H bond func-
tionalization of MOFs, with simultaneous preservation of
the topology of the system, would significantly increase
MOF structural diversity and could become a prototype for
PSM of MOFs. Herein, we demonstrate the first step to-
À
Functional groups are groups of atoms responsible for the
characteristic chemical reactivity of a molecule. Nonacidic
wards this goal: direct C H phenylation of an indole-de-
rived UMCM-1 (University of Michigan Crystalline Materi-
al-1)-type MOF through highly selective and efficient palla-
dium catalysis.
À
C H bonds are ubiquitous in organic matter and are gener-
[a] T. Drçge,+ A. Notzon,+ Dr. R. Frçhlich, Prof. Dr. F. Glorius
Organisch-Chemisches Institut
MOF-5 and UMCM-1 represent two of the most well-
known MOF structures. The structure of MOF-5 contains
Zn4O clusters and 1,4-benzenedicarboxylate (BDC),[24]
whereas UMCM-1 consists of not only Zn4O clusters and
BDC, but also benzene-1,3,5-triyl-tribenzoate (BTB) link-
ers.[25] Thus, we commenced our study by assembling MOFs,
utilizing 1-methylindole-4,7-dicarboxylic acid (1) as a BDC
analogue. After extensive experimentation, the MOFs
Westfꢀlische Wilhelms-Universitꢀt Mꢁnster
Corrensstrasse 40, 48149 Mꢁnster (Germany)
Fax : (+49)251-83-33202
E-mail: glorius@uni-muenster.de
[+] These authors contributed equally to this work.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201101850.
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COMMUNICATION
MOF-5-indole (2) and UMCM-
1-indole (3) were obtained as
yellow needles in yields of 86
and
(Scheme 1,
16%,
respectively
top).[26]
These
MOFs were fully characterized
by powder X-ray diffraction
(PXRD)
structure
and
analysis,
single-crystal
which
showed that their topologies
were similar to those of MOF-5
and UMCM-1 (Figure 1). In ad-
dition, our PXRD measure-
ments indicated that UMCM-1-
indole (3) became amorphous
upon drying. Consequently, gas
adsorption measurement of 3
showed a maximum nitrogen
uptake of only 155 cm3 gÀ1. The
corresponding
Brunauer–
Emmett–Teller (BET) surface
area is calculated to be (448Æ
5) m2 gÀ1, a factor of ten lower
than what is reported for
UMCM-1.[25,26] Such drastic dif-
ference could be attributed to
the instability of the unmodified
Scheme 1. Formation of indole–BDC-derived MOFs (2 and 3) (top) and (attempted) Pd-catalyzed phenyla-
tions (bottom).
MOF, which collapsed upon drying. NMR spectroscopy and
mass spectrometric analysis after acid hydrolysis further
confirmed the structural integrity of the MOF linkers and,
in the case of 3, also determined the ratio of the linker mol-
ecules to be 1.33:1 (BTB/indole–BDC).
We commenced our study on the selective functionaliza-
tion of 2 and 3 by using [Ph2I]BF4 as the phenylating agent
and AcOH as the solvent.[27–29] However, attempts to apply
this previously developed condition[20c] for the PSM of the
MOFs 2 and 3 proved to be ineffective due to the sensitivity
of both MOF-5-indole and UMCM-1-indole to the highly
acidic reaction conditions (Scheme 1).[26] Because we re-ex-
amined the reactivity of the indole linker 1 in homogeneous
solution, the reaction medium was strategically chosen to
preserve the integrity of the MOF. Pleasingly, the 2-pheny-
lated indole 4 was obtained, when the solvent was changed
from acetic acid to DMF. However, at room temperature,
the reaction was not complete even after 13 days (44%
yield). Full conversion was only achieved with 20 mol% of
Figure 1. Single-crystal structures of MOF-5-indole (2) (left) and
UMCM-1-indole (3) (right). The pyrrole ring of linker 1 (indicated by *)
and the carbon and nitrogen atoms of the coordinated solvent molecules
could not be found. Furthermore, no solvent molecules could be identi-
fied in the voids therefore the SQUEEZE routine was used.
ty could be attributed to the small window size of the MOF,
which restricts the entry of the reagents into the MOF.
Based on this analysis, UMCM-1-type MOFs, which contain
larger pores and windows, appear to be well suited for this
transformation. Indeed, by treating UMCM-1-indole (3)
under the optimized conditions in DMF, complete conver-
sion to the phenylated UMCM-1-Ph-indole (5) was achieved
within five days at room temperature with excellent regiose-
lectivity (C2/C3>95:5; Scheme 1). The selective and quanti-
tative 2-phenylation was determined by 1H and 13C NMR
spectroscopy (Figure 2) and mass spectrometry of samples
obtained after digesting the MOF under acidic conditions.[26]
Moreover, both the crystallinity and the topology of the
MOF were conserved, as revealed by PXRD (Figure S14 in
the Supporting Information) and single-crystal structural
catalyst (PdACHTUNGTRENNUNG(OAc)2), employed at 608C for six days, afford-
ing the desired product isolated in 71% yield.[26] Fortunately,
an undesired PdII-catalyzed dimerization of the N-methylin-
dole, which leads to the deactivation of the catalyst by form-
ing Pd0, is not possible within the rigid framework.[30]
With the optimal conditions established for the free or-
ganic linker, we began our effort to selectively functionalize
the MOFs. Our initial attempt with MOF-5-indole (2) under
the optimized conditions was unsuccessful, since only trace
amounts of the phenylated indole were observed at either
room temperature or 608C (Scheme 1). The lack of reactivi-
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11975

F. Glorius, T. Drçge et al.
&
*
Figure 3. N2 adsorption ( =UMCM-1-Ph-indole; =UMCM-1-indole)
*
and desorption
(
=UMCM-1-Ph-indole; & =UMCM-1-indole) iso-
Figure 2. Comparison of 1H NMR spectra: a) 1H NMR spectra of the
indole-linker 1; b) 1H NMR spectra of the phenylated indole-linker (4);
c) 1H NMR spectra of the mixture of the indole- and BTB-linker after di-
gesting the modified UMCM-1-indole MOF (5).
therms at 77 K of UMCM-1-indole (3) and UMCM-1-Ph-indole (5), re-
spectively.
should dramatically expand the scope of accessible MOF
structures and allow ample and facile variation of the prop-
1
À
analysis. Importantly, mass spectrometry and H NMR spec-
erties of MOFs. Site-specific C H functionalization should
troscopy analysis of the supernatant solution after the com-
pletion of the reaction showed no trace of any free linker
molecules. This result again indicates that the integrity of
the MOF was preserved during the reaction and thus ex-
cludes any homogeneous reaction pathways. As expected,
without the palladium catalyst, no desired functionalized
MOF was observed even after prolonged reaction time. In-
triguingly, trying to independently synthesize 5 from the 2-
phenylated indole linker 4, under the same conditions used
to prepare UMCM-1-indole (3), resulted in the formation of
crystals that had a different PXRD (Figure S15 in the Sup-
porting Information).
The maximal N2 uptake of UMCM-1-Ph-indole (5) was
four times larger than the one observed for UMCM-1-
indole (Figure 3; 645 vs. 154 cm3 gÀ1; BET surface areas of
(2085Æ96) vs. (448Æ5) m2 gÀ1). Although the unmodified
UMCM-1-indole turns amorphous and collapses upon
drying, the modified UMCM-1-Ph-indole remains crystal-
line. However, after washing the modified UMCM-1-Ph-
indole, 7.22 wt% of palladium remained. It represents one
thus become an important tool for the preparation of mate-
rials with tailor-made and fine-tuned properties.
Experimental Section
UMCM-1-indole MOF (0.1 mmol according to the indole–BDC linker),
PdACHTNUTRGENNG(U OAc)2 (0.02 mmol), and diphenyliodonium tetrafluoroborate
(0.15 mmol) were placed into an oven-dried test tube vial with screw cap
under air. The crystalline MOF material was taken out of a DMF-filled
test tube vial with screw cap and placed on a glass plate. The majority of
the residual DMF was removed with a pipette, and the wet crystals were
transferred with a spatula into the reaction vial. Solvent was added by sy-
ringe and the flask was then closed and shaken at RT for the time indi-
cated in the Supporting Information. A part of the crystalline material
was taken out of the reaction mixture and the supernatant solution was
decanted. The decanted solution was evaporated and analyzed by mass
spectrometry and NMR spectroscopy, which showed no modified indole
linker within the detectable range. The material was then washed three
times with DMF, then three times with CHCl3. Concentrated aqueous
HCl was added to digest the MOF and afterwards removed under high
vacuum. The residual solid material was taken up in MeOH, filtered
through a Whatman filter, and subjected to HPLC-MS analysis.
À
rare example for the application of C H activation chemis-
try in the field of materials. Thus, transition-metal-catalyzed
À
C H functionalizations, with their ability to create function-
Acknowledgements
À
al groups from ubiquitous C H bonds, should significantly
expand the scope of MOFs and other materials.[31]
In conclusion, we have successfully achieved the postsyn-
thetic modification of a MOF by C H activation chemistry.
The reaction proceeds quantitatively under mild conditions
with remarkable chemo- and regioselectivity. During this
process, the crystallinity of the MOF remains intact. This
should inspire further investigation and development of
other metal-catalyzed postsynthetic modifications of MOFs.
We thank Prof. H. Eckert, Prof. M. Winter, and Prof. R. Pçttgen, and
their co-workers for performing TGA, DSC, gas sorption, ICP-OES, and
PXRD measurements. In addition, we thank Mohan Padmanaban and
Fan Liu for helpful discussions. Generous financial support by the Euro-
pean Research Council (Starting Investigator Grant) and the Deutsche
Forschungsgemeinschaft (SPP 1362) is gratefully acknowledged. The re-
search of F.G. is supported by the Alfried Krupp Prize for Young Univer-
sity Teachers of the Alfried Krupp von Bohlen und Halbach Foundation.
À
À
The selective and efficient C H functionalization of MOFs
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Palladium-Catalyzed C H Bond Functionalization
COMMUNICATION
À
[17] K. K. Tanabe, C. A. Allen, S. M. Cohen, Angew. Chem. 2010, 122,
9924–9927; Angew. Chem. Int. Ed. 2010, 49, 9730–9733.
Keywords: chemoselectivity
organic frameworks · palladium · postsynthetic modification
·
C H activation
·
metal–
À
[18] a) Special issue: C H Functionalisation in Organic Synthesis, Chem.
Soc. Rev. 2011, 40, Issue 4; b) Special issue: Selective Functionaliza-
À
tion of C H Bonds, Chem. Rev. 2010, 110, Issue 2.
[1] a) J. R. Long, O. M. Yaghi, Chem. Soc. Rev. 2009, 38, 1213–1214;
b) L. Ma, C. Abney, W. Lin, Chem. Soc. Rev. 2009, 38, 1248–1256;
c) J. Lee, O. K. Farha, J. Roberts, K. A. Scheidt, S. T. Nguyen, J. T.
Hupp, Chem. Soc. Rev. 2009, 38, 1450–1459; d) J.-R. Li, R. J. Kup-
pler, H.-C. Zhou, Chem. Soc. Rev. 2009, 38, 1477–1504; e) D. J.
Tranchemontagne, J. L. Mendoza-Cortꢃs, M. OꢄKeeffe, O. M. Yaghi,
Chem. Soc. Rev. 2009, 38, 1257–1283; f) G. Nickerl, A. Henschel, R.
Gruenker, K. Gedrich, S. Kaskel, Chem. Ing. Tech. 2011, 83, 90–
103; for our work on the design of MOFs and element organic
frameworks as (chiral)catalysts, see: g) K. Gedrich, M. Heitbaum,
A. Notzon, I. Senkovska, R. Frçhlich, J. Getzschmann, U. Mueller,
F. Glorius, S. Kaskel, Chem. Eur. J. 2011, 17, 2099–2106; h) M.
Rose, A. Notzon, M. Heitbaum, G. Nickerl, S. Paasch, E. Brunner,
F. Glorius, S. Kaskel, Chem. Commun. 2011, 47, 4814–4816.
[19] a) C. S. Yeung, V. M. Dong, Chem. Rev. 2011, 111, 1215–1292; b) L.
Ackermann, Chem. Rev. 2011, 111, 1315–1345; c) J. Wencel-Delord,
T. Drçge, F. Liu, F. Glorius, Chem. Soc. Rev. 2011, 40, 4740–4761;
d) T. W. Lyons, M. S. Sanford, Chem. Rev. 2010, 110, 1147–1169;
e) C.-L. Sun, B.-J. Li, Z.-J. Shi, Chem. Commun. 2010, 46, 677–685;
f) R. Giri, B.-F. Shi, K. M. Engle, N. Maugel, J.-Q. Yu, Chem. Soc.
Rev. 2009, 38, 3242–3272; g) D. Alberico, M. E. Scott, M. Lautens,
Chem. Rev. 2007, 107, 174–238.
À
[20] For a review on mild C H activation reactions, see: a) reference
[19c]; for mild Pd-catalyzed indole functionalizations, see: b) N.
Lebrasseur, I. Larrosa, J. Am. Chem. Soc. 2008, 130, 2926–2927;
c) N. R. Deprez, D. Kalyani, A. Krause, M. S. Sanford, J. Am. Chem.
Soc. 2006, 128, 4972–4973; d) N. P. Grimster, C. Gauntlett, C. R. A.
Godfrey, M. J. Gaunt, Angew. Chem. 2005, 117, 3185–3189; Angew.
Chem. Int. Ed. 2005, 44, 3125–3129; for the de novo synthesis of in-
doles from anilines, see: e) S. Wꢁrtz, S. Rakshit, J. J. Neumann, T.
Drçge, F. Glorius, Angew. Chem. 2008, 120, 7340–7343; Angew.
Chem. Int. Ed. 2008, 47, 7230–7233; f) J. J. Neumann, S. Rakshit, T.
Drçge, S. Wꢁrtz, F. Glorius, Chem. Eur. J. 2011, 17, 7298–7303.
[21] D. R. Stuart, K. Fagnou, Science 2007, 316, 1172–1175.
[22] For a mild Ru-catalyzed indole functionalization, see: H. F. T. Klare,
M. Oestreich, J. Ito, H. Nishiyama, Y. Ohki, K. Tatsumi, J. Am.
Chem. Soc. 2011, 133, 3312–3315.
[23] For Pd-catalyzed functionalizations, see: a) C. Jia, D. Piao, J. Oya-
mada, W. Lu, T. Kitamura, Y. Fujiwara, Science 2000, 287, 1992–
1995; for Rh-catalyzed functionalization, see: b) H. Chen, S.
Schlecht, T. C. Semple, J. F. Hartwig, Science 2000, 287, 1995–1997;
for Cu-catalyzed functionalization, see: c) R. J. Phipps, M. J. Gaunt,
Science 2009, 323, 1593–1597.
[2] U. Mueller, M. Schubert, F. Teich, H. Puetter, K. Schierle-Arndt, J.
Pastrꢃ, J. Mater. Chem. 2006, 16, 626–636.
[3] S. Kitagawa, R. Kitaura, S. Noro, Angew. Chem. 2004, 116, 2388–
2430; Angew. Chem. Int. Ed. 2004, 43, 2334–2375.
˘
[4] M. Dinca, J. R. Long, Angew. Chem. 2008, 120, 6870–6884; Angew.
Chem. Int. Ed. 2008, 47, 6766–6779.
[5] O. M. Yaghi, M. OꢄKeeffe, N. W. Ockwig, H. K. Chae, M. Eddaoudi,
J. Kim, Nature 2003, 423, 705–714.
[6] A. C. McKinlay, R. E. Morris, P. Horcajada, G. Fꢃrey, R. Gref, P.
Couvreur, C. Serre, Angew. Chem. 2010, 122, 6400–6406; Angew.
Chem. Int. Ed. 2010, 49, 6260–6266.
[7] B. F. Hoskins, R. Robson, J. Am. Chem. Soc. 1990, 112, 1546–1554.
[8] a) M. J. Ingleson, J. P. Barrio, J.-B. Guilbaud, Y. Z. Khimyak, M. J.
Rosseinsky, Chem. Commun. 2008, 2680–2682; b) G. Fꢃrey, C.
Mellot-Draznieks, C. Serre, F. Millange, J. Dutour, S. Surblꢃ, I. Mar-
giolaki, Science 2005, 309, 2040–2042.
[24] H. Li, M. Eddaoudi, M. OꢄKeeffe, O. M. Yaghi, Nature 1999, 402,
276–279.
[25] K. Koh, A. G. Wonh-Foy, A. J. Matzger, Angew. Chem. 2008, 120,
689–692; Angew. Chem. Int. Ed. 2008, 47, 677–680.
[9] a) K. K. Tanabe, S. M. Cohen, Chem. Soc. Rev. 2011, 40, 498–519;
b) S. M. Cohen, Chem. Sci. 2010, 1, 32–36; c) Z. Wang, S. M. Cohen,
Chem. Soc. Rev. 2009, 38, 1315–1329.
[10] S. Bernt, V. Guillerm, C. Serre, N. Stock, Chem. Commun. 2011, 47,
2838–2840.
[11] J. S. Seo, D. Whang, H. Lee, S. I. Jun, J. Oh, Y. J. Jeon, K. Kim,
Nature 2000, 404, 982–986.
[26] See the Supporting Information for further details.
[27] S. Cacchi, G. Fabrizi, Chem. Rev. 2005, 105, 2873–2920.
[28] L.-M. Xu, B.-J. Li, Z. Yang, Z.-J. Shi, Chem. Soc. Rev. 2010, 39, 712–
733.
[12] K. L. Mulfort, O. K. Farha, C. L. Stern, A. A. Sarjeant, J. T. Hupp, J.
Am. Chem. Soc. 2009, 131, 3866–3868.
[29] R. J. Phipps, N. P. Grimster, M. J. Gaunt, J. Am. Chem. Soc. 2008,
130, 8172–8174.
[13] a) Y.-H. Kiang, G. B. Gardner, S. Lee, Z. Xu, E. B. Lobkovsky, J.
Am. Chem. Soc. 1999, 121, 8204–8215; b) Z. Wang, S. M. Cohen, J.
Am. Chem. Soc. 2007, 129, 12368–12369.
[30] a) Z. Liang, J. Zhao, Y. Zhang, J. Org. Chem. 2010, 75, 170–177;
b) Y. Li, W.-H. Wang, S.-D. Yang, B.-J. Li, C. Feng, Z.-J. Shi, Chem.
Commun. 2010, 46, 4553–4555.
[14] W. Morris, C. J. Doonan, H. Furukawa, R. Banerjee, O. M. Yaghi, J.
Am. Chem. Soc. 2008, 130, 12626–12627.
[15] a) T. Gadzikwa, G. Lu, C. L. Stern, S. R. Wilson, J. T. Hupp, S. T.
Nguyen, Chem. Commun. 2008, 5493–5495; b) Y. Goto, H. Sato, S.
Shinkai, K. Sada, J. Am. Chem. Soc. 2008, 130, 14354–14355.
[16] S. C. Jones, C. A. Bauer, J. Am. Chem. Soc. 2009, 131, 12516–12517.
[31] a) C. Volkringer, S. M. Cohen, Angew. Chem. 2010, 122, 4748–4752;
Angew. Chem. Int. Ed. 2010, 49, 4644–4648; b) J. G. Nguyen, S. M.
Cohen, J. Am. Chem. Soc. 2010, 132, 4560–4561.
Received: June 16, 2011
Published online: September 16, 2011
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