N—H Insertion Reactions Catalyzed by a Dirhodium Metal-Organic Cage: A Facile and Recyclable Approach for C—N Bond Formation

Article abstract of DOI:10.1002/cjoc.201600818

A heterogeneous metal-organic cage based on Rh-Rh bonds [Rh₄(pbeddb)₄(H₂O)₂(DMAC)₂] (MOC-18; pbeddb^2? = 3,3'-(1,3-phenylenebis(ethyne-2,1-diyl))dibenzoate) was applied to the N—H insertion

Full text of DOI:10.1002/cjoc.201600818

FULL PAPER
DOI: 10.1002/cjoc.201600818
N－H Insertion Reactions Catalyzed by a Dirhodium
Metal-Organic Cage: A Facile and Recyclable Approach for
C－N Bond Formation
Jian Kang,a Lianfen Chen,a Hao Cui,a Li Zhang,*,a and Cheng-Yong Su*,a,b
a MOE Laboratory of Bioinorganic and Synthetic Chemistry, Lehn Institute of Functional Materials,
School of Chemistry, Sun Yat-sen University, Guangzhou, Guangdong 510275, China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai 200032, China
A heterogeneous metal-organic cage based on Rh-Rh bonds [Rh4(pbeddb)4(H2O)2(DMAC)2] (MOC-18;
pbeddb2＝3,3'-(1,3-phenylenebis(ethyne-2,1-diyl))dibenzoate) was applied to the N－H insertion reactions with
diazo compounds. This method offered an environmentally friendly and highly efficient approach for C－N bond
formation.
Keywords porous frameworks, metal-organic cage, heterogeneous catalysis, C－N bond formation, N－H inser-
tion
Introduction
Porous frameworks based on metal-ligand bonds, in-
cluding metal-organic frameworks (MOFs), met-
al-organic gels (MOGs), metal-organic cages (MOCs),
etc., have emerged as a new kind of heterogeneous cat-
alysts, which have displayed a large spectrum of ad-
vantages.[1,2] The porous structure endows the catalysts
with accessible active sites, considering that both of the
external and internal surfaces can be exposed to the
coming substances and then the catalytic reactions can
be carried out in the cavities as well as the exteriors.
Dirhodium(II) complexes are important homogene-
ous catalysts, and can promote various reactions, espe-
cially the carbene and nitrene transfer reactions.[3-5] As
one of the noble metals, recyclability and reuse of
Rh-based catalysts become one of the most important
and urgent issues, although the rhodium price has
dropped 50% in the last 5 years.[6] Incorporations of
dirhodium units into porous frameworks have recently
been reported by Mori,[7] Kaskel,[8] and us.[9] After the
immobilization of dirhodium catalysts into the frame-
works, they can be reused for up to ten runs without the
loss of the efficiency.
Figure 1 MOC-18-catalyzed N－H insertion reactions.
bamates) have appealed as the highly efficient meth-
ods.[11]
We have recently reported a metal-organic cage
(MOC-18) containing Rh-Rh bonds with the formula of
Rh4(pbeddb)4 (pbeddb2＝3,3'-(1,3-phenylenebis-
(ethyne-2,1-diyl))dibenzoate).[9a] The dimensions of the
inner cavity are 9.5 Å×14.8 Å. In the solid phase, the
To develop environmentally friendly and highly effi-
cient catalytic methods of C－N bond formation, a lot
of efforts have been paid.[10] Among them, dirhodi-
um-catalyzed nitrene transfer reactions or carbene inser-
tion into N－H bonds (e.g. in amines, amides, and car-
*
E-mail: hli99@mail.sysu.edu.cn, cesscy@mail.sysu.edu; Tel: 0086-20-84110318, Fax: 0086-20-84115178
Received November 22, 2016; accepted March 18, 2017; published online June 5, 2017.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201600818 or from the author.
In Memory of Professor Enze Min.
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Chin. J. Chem. 2017, 35, 964—968

N－H Insertion Reactions Catalyzed by a Dirhodium Metal-Organic Cage
Recycling experiments and ICP analysis for the
leached rhodium
cages are aligned by π-π stacking to form one-dimen-
sional channels (9.5 Å×11.1 Å) through cage windows.
Such structure feature will help MOC-18 to promote
both the in-cage and out-cage reactions with high effi-
ciency. As expected, MOC-18 has been proved to be an
excellent heterogeneous catalyst for nitrene transfer re-
actions of intramolecular C－H amination in our previ-
ous work. Herein, we demonstrate that MOC-18 is a
highly efficient heterogeneous catalyst for carbene in-
sertion into N－H bonds (Figure 1).
4-Fluorobenzamide (292 mg, 2.1 mmol) and
MOC-18 (10.5 mg, 0.00525 mmol, 0.25 mol%) were
dissolved in DCM (6 mL), and then a DCM (4 mL) so-
lution containing methyl 2-diazo-2-phenylacetate
(MPDA, 554 mg, 3.15 mmol) was dropped slowly to the
reaction mixture within 30 min at room temperature.
After the reaction was completed, the resulting solution
was centrifuged to recycle the catalyst. The obtained
catalyst was washed with DCM (2 mL×5) and heated
at 110 ℃ in vacuum for 6 h, which was then reused in
the next runs. The recycling experiments were conduct-
ed for 9 runs.
Experimental
General
All the reagents in the present work were obtained
from the commercial source and used directly without
further purification. HRESI-MS was performed by us-
After the removal of the catalyst in the first run, the
reaction solution was collected and concentrated to
dryness via vacuum. The residue was digested by nitric
acid and concentrated hydrochloric acid in a 10 mL ce-
ramic crucible until a clear and colorless solution was
obtained. The obtained solution was concentrated to
about 3 mL, which was then diluted to 25 mL with
aqueous solution of nitric acid (2%). After then, 15 mL
of the solution was taken out and then further diluted to
125 mL with aqueous solution of nitric acid (2%). The
final solution was analyzed by an inductively coupled
plasma-optical emission spectrometer. The measured Rh
content was 0.032 ppm (0.00667 mg) and the leached
rhodium was 0.62% (0.00667 mg/1.08045 mg 100%).
The Rh contents were measured in ppm based on cali-
bration curves obtained with a series of calibration
standard solutions doped with different amounts of Rh.
1
ing a Bruker Daltonics ESI-Q-TOF maXis4G. H NMR
and 13C NMR spectra were recorded on a Bruker
AVANCE III 400 or a Bruker AVANCE III 300. Chemi-
cal shifts were quoted in parts per million referenced to
the appropriate solvent peak or δ 0 for TMS. Specific
rotations were measured on ADP440＋B＋S. ICP spec-
troscopy was conducted on a SpectroCiros Vision
ICP-OES spectrometer. PXRD patterns were recorded
on SmartLab X-ray powder diffractometer (Rigaku Co.)
at 40 kV and 30 mA with a Cu target tube.
Cautions
Although we have not experienced any problem in
the handling of the diazo compounds, extreme care
should be taken when manipulating them due to their
explosive nature.
Results and Discussion
Synthesis of MOC-18
Methyl phenyldiazoacetate (MPDA) is a commonly
used carbene precursor and can be readily prepared by
methyl phenylacetate.[12] Considering that diazo com-
pounds are easily decomposed and dimerized in the
presence of dirhodium complexes, the reactions were
conducted at room temperature with slow drop of
MPDA. In the typical procedure, 0.25 mol% MOC-18
was loaded and DCM was used as solvent. Different
N－H containing compounds have been screened for
N－H insertion reaction, and it has been found that
4-fluorobenzamide reacts with MPDA efficiently in the
NMR yield of 95% (Table 1, Entry 1). Decreasing the
amount of the catalyst to 0.125 mol% or 0.0625 mol%,
the NMR yield is still as high as 95% (Entries 2 and 3).
To compare the reactivity with other dirhodium
complexes, Rh2(OAc)4 was used instead of MOC-18 in
the reaction of MPDA and 4-fluorobenzamide under the
similar reaction condition. When 0.25 mol% Rh2(OAc)4
was used, the reaction was accomplished in 95% yield
(Entry 4), but however, only 25% yield was obtained if
the catalyst amount was reduced to 0.125 mol% (Entry
5). Through the comparison, MOC-18 shows much bet-
ter performances than Rh2(OAc)4 (Entry 3 vs. 5).
MOC-18 displays a lantern-type structure, and a pair of
MOC-18 was synthesized by the following proce-
dure:[9a] Rh2(OAc)4 (4.4 mg, 0.01 mmol), H2pbeddb (9.2
mg, 0.025 mmol), Na2CO3 (3 mg, 0.028 mmol) and di-
methylacetamide (DMAC, 2 mL) were added into a 10
mL vial with a cap. After the whole mixture was dis-
solved by ultrasound, the vial was kept at 100 ℃ in an
oven for about 48 h to produce the crystals. The bulk
purity of as-synthesized crystals was confirmed by the
PXRD patterns similar to the simulated ones. Before
each catalytic reaction, the as-synthesized sample of
MOC-18 has been activated by heating at 110 ℃ under
vacuum for 6 h.
Typical procedure for catalytic N－H insertion
4-Fluorobenzamide (83 mg, 0.6 mmol, 1.0 equiv.),
MOC-18 (3 mg, 0.0015 mmol, 0.25 mol%) and
dichoromethane (DCM, 2 mL) were added into a 10 mL
vial, and then methyl 2-diazo-2-phenylacetate (158 mg,
0.9 mmol, 1.5 equiv., dissolved in 1 mL DCM) was
added dropwise with stirring at room temperature within
30 min. The resulting solution was stirred for another 30
min. The isolated yield of methyl 2-(4-fluorobenz-
amido)-2-phenylacetate (2a) was 92%.
Chin. J. Chem. 2017, 35, 964—968
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Kang et al.
FULL PAPER
paddlewheel units are bridged, which endows MOC-18
with higher stability than non-bridged catalyst
Rh2(OAc)4 and less ligand exchange possibility.[13]
In the presence of MOC-18, benzyl carbamate can
also react with MPDA efficiently in the NMR yield of
95% (Entry 7), but however, aniline did not work at all
(Entry 8). When MOC-18 was added to the reaction
solution with aniline, the catalyst turned from green to
yellow while no nitrogen bubble was released during the
addition of MPDA. In comparison, Rh2(OAc)4 can
largely promote the reaction of MPDA and aniline, and
the N－H insertion product can be achieved in 95%
(Entry 9). Due to the conjugation of amide group
(－CONH－), the amide and carbamate groups have
weaker coordination effect, and the N－H insertion
products are easier to dissociate from the dirhodium
catalysts, whereas the amino group is relatively more
tightly bound to the dirhodium paddlewheel units of the
catalysts.[13,14] The difference of the coordination effect
has been further enlarged by the confinement effect of
MOC-18, which might explain the inactivity of aniline.
It is noted that in the presence of aniline, MOC-18 can
not promote the N－H insertion reaction of 4-fluoroben-
zamide (Entry 6).
Table 1 Catalytic N－H insertion reaction with different N－H
bonds
Entry Substrate
Product
Yielda/%
95
95b
95c
95d
1
2
3
4
O
CO2Me
O
NH2
N
H
F
F
5
25e
6
7
＜5f
95
CO2Me
NH2
8
9
＜5
95d
N
H
a The molar ratio of amide and MPDA is 1∶1.5. The NMR yield
To evaluate the catalytic capability of MOC-18, dif-
ferent substituted amides are applied to this reaction in
the following research (Table 2). For both elec-
tron-deficient and electron-rich para-substituted aro-
matic amides, good yields are obtained (85%－93%, 2a
was determined by the conversion of amine/amide/carbamate to
b
c
the N－H insertion product. 0.125 mol%. 0.0625 mol%.
d Rh2(OAc)4, 0.25 mol%. Rh2(OAc)4, 0.125 mol%. In the pres-
e
f
ence of 1 equiv. of aniline.
Table 2 Substrate scope of catalytic N－H insertion reactiona
O
CO2Me
Ph
O
CO2Me
N Ph
N
H
H
O2N
Cl
2b, 86%
2c, 85%
CO2Me
Ph
O
O
CO2Me
Ph
N
N
H
H
MeO
2d, 90%
2f, 93%
O
CO2Me
N Ph
O
H
2l, 90%
a Isolated yield.
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Chin. J. Chem. 2017, 35, 964—968

N－H Insertion Reactions Catalyzed by a Dirhodium Metal-Organic Cage
－2f). ortho-Substituents seemed to have no obvious
difference in yield (2g and 2h). Non-aromatic amide
substrates also resulted in an excellent yield (2i, 95%).
Carbamates are also good substances for this catalytic
reaction, and the N－H insertion products were gener-
ated in up to 95% yield (2j－2l).
MOC-18 has been further employed in the modifica-
tion of cholesterol derivative (3) tailoring with a carba-
mate group. In the presence of 0.25 mol% of MOC-18,
the N－H insertion reaction was accomplished in 95%
conversion (Scheme 1). Dirhodium complexes are usu-
ally used for the cyclopropanation reaction. It is noted
that no cyclopropane product has been detected in the
MOC-18-catalyzed reaction, although one C－C double
bond is present in 3,[3] which highlights its high
chemoselectivity towards N－H insertion.
Scheme 1 Modification of cholesterol derivative
Figure 2 Recycling experiments.
MOC-18 is an excellent and environmentally friendly
heterogeneous dirhodium catalyst.
Acknowledgement
This work was supported by the 973 Program
(2012CB821701), the NSFC Projects (Nos. 21373278,
91222201), the STP Project of Guangzhou (No.
15020016), the NSF of Guangdong Province (No.
S2013030013474), the RFDP of Higher Education of
China (No. 20120171130006) and the Fundamental Re-
search Funds for the Central Universities.
MOC-18 has been further proved to be an efficient
heterogeneous catalyst for N－H insertion reactions of
amides and diazoacetates. After the reaction of MPDA
and 4-fluorobenzamide was completed, MOC-18 could
be easily separated by centrifugation. The isolated
MOC-18 can be reused in the next reaction after activa-
tion by heating at 110 ℃ under vacuum for 6 h. The
results of the recycling experiments showed that the
yields were obtained in the range of 83%－98% in the
eight runs, whereas it was reduced to 62% in the ninth
run, which might be due to the stacked products in the
cavities of the MOC-18 (Figure 2). The total turnover
number (TON) was calculated to be 3180. The ICP
analysis showed that only 0.62% rhodium was leached
in the reaction, suggesting that the catalytic reaction was
indeed catalyzed by the solid MOC-18 catalyst.
References
[1] (a) Liu, J.; Chen, L.; Cui, H.; Zhang, J.; Zhang, L.; Su, C.-Y. Chem.
Soc. Rev. 2014, 43, 6011; (b) Cook, T. R.; Zheng, Y.-R.; Stang, P. J.
Chem. Rev. 2013, 113, 734; (c) Smulders, M. M. J.; Riddell, I. A.;
Browne, C.; Nitschke, J. R. Chem. Soc. Rev. 2013, 42, 1728; (d)
Amouri, H.; Desmarets, C.; Moussa, J. Chem. Rev. 2012, 112, 2015;
(e) Yoshizawa, M.; Klosterman, J. K.; Fujita, M. Angew. Chem., Int.
Ed. 2009, 48, 3418; (f) Oliveri, C. G.; Ulmann, P. A.; Wiester, M. J.;
Mirkin, C. A. Acc. Chem. Res. 2008, 41, 1618; (g) Fiedler, D.;
Leung, D. H.; Bergman, R. G.; Raymond, K. N. Acc. Chem. Res.
2005, 38, 351.
[2] (a) Li, L.; Cao, X.; Huang, R. Chin. J. Chem. 2016, 34, 143; (b) Pei,
X.; Chen, Y.; Li, S.; Zhang, S.; Feng, X.; Zhou, J.; Wang, B. Chin. J.
Chem. 2016, 34, 157; (c) Liu, L.; Ye, Y.; Yao, Z.; Zhang, L.; Li, Z.;
Wang, L.; Ma, X.; Chen, Q.-H.; Zhang, Z.; Xiang, S. Chin. J. Chem.
2016, 34, 215; (d) Cao, Y.; Wang, R.; Wu, G.; Fang, Q.; Qiu, S. Chin.
J. Chem. 2016, 34, 196.
[3] (a) Davies, H. M. L.; Denton, J. R. Chem. Soc. Rev. 2009, 38, 3061;
(b) Doyle, M. P.; Duffy, R.; Ratnikov, M.; Zhou, L. Chem. Rev. 2010,
110, 704; (c) Doyle, M. P.; Hu, W.-H. Chin. J. Chem. 2001, 19, 22;
(d) Gillingham, D.; Fei, N. Chem. Soc. Rev. 2013, 42, 4918.
[4] (a) Paulissen, R.; Hayez, E.; Hubert, A. J.; Teyssie, P. Tetrahedron
Lett. 1974, 15, 607; (b) Aller, E.; Buck, R. T.; Drysdale, M. J.; Ferris,
L.; Haigh, D.; Moody, C. J.; Pearson, N. D.; Sanghera, J. B. J. Chem.
Soc., Perkin Trans. 1 1996, 2879; (c) Ferris, L.; Haigh, D.; Moody,
Conclusions
A remarkable heterogeneous metal-organic cage cat-
alyst MOC-18 has been explored in the N－H insertion
reactions with diazo compounds, which is highly effi-
cient for a range of amides and carbamates, including
bioactive compounds. Besides, MOC-18 is recyclable
and can be reused for at least nine runs. In general,
Chin. J. Chem. 2017, 35, 964—968
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www.cjc.wiley-vch.de
967

Kang et al.
FULL PAPER
C. J. J. Chem. Soc., Perkin Trans. 1 1996, 2885; (d) Buck, R. T.;
Clarke, P. A.; Coe, D. M.; Drysdale, M. J.; Ferris, L.; Haigh, D.;
Moody, C. J.; Pearson, N. D.; Swann, E. Chem. Eur. J. 2000, 6,
2160.
Chem. A 2015, 3, 20201; (b) Zhu, B.; Liu, G.; Chen, L.; Qiu, L.;
Chen, L.; Zhang, J.; Zhang, L.; Barboiu, M.; Si, R.; Su, C.-Y. Inorg.
Chem. Front. 2016, 3, 702.
[10] (a) Roizen, J. L.; Harvey, M. E.; Du Bois, J. Accounts Chem. Res.
2012, 45, 911; (b) Huang, L.; Jin, C.; Su, W. Chin. J. Chem. 2012,
30, 2394; (c) Bariwal, J.; Van der Eycken, E. Chem. Soc. Rev. 2013,
42, 9283; (d) Shin, K.; Kim, H.; Chang, S. Acc. Chem. Res. 2015, 48,
1040.
[11] Ford, A.; Miel, H.; Ring, A.; Slattery, C. N.; Maguire, A. R.;
McKervey, M. A. Chem. Rev. 2015, 115, 9981.
[12] Davies, H. M. L. Eur. J. Org. Chem.1999, 2459.
[5] (a) Zhu, D.; Ma, J.; Luo, K.; Fu, H.; Zhang, L.; Zhu, S. Angew.
Chem., Int. Ed. 2016, 55, 8452; (b) Ma, J.; Chen, K.; Fu, H.; Zhang,
L.; Wu, W.; Jiang, H.; Zhu, S. Org. Lett. 2016, 18, 1322; (c) Kang, J.;
Zhu, B.; Liu, J.; Wang, B.; Zhang, L.; Su, C.-Y. Org. Chem. Front.
2015, 2, 890.
[6] Candeias, N. R.; Afonso, C. A. M.; Gois, P. M. P. Org. Biomol.
Chem. 2012, 10, 3357.
[7] (a) Mori, W.; Sato, T.; Ohmura, T.; Kato, C. N.; Takei, T. J. Solid
State Chem. 2005, 178, 2555; (b) Kataoka, Y.; Sato, K.; Miyazaki, Y.;
Masuda, K.; Tanaka, H.; Naito, S.; Mori, W. Energy Environ. Sci.
2009, 2, 397; (c) Sato, T.; Mori, W.; Kato, C. N.; Yanaoka, E.; Ku-
ribayashi, T.; Ohtera, R.; Shiraishi, Y. J. Catal. 2005, 232, 186.
[8] Nickerl, G.; Stoeck, U.; Burkhardt, U.; Senkovska, I.; Kaskel, S. J.
Mater. Chem. A 2014, 2, 144.
[13] (a) Taber, D. F.; Meagley, R. P.; Louey, J. P.; Rheingold, A. L. Inorg.
Chem. Acta 1995, 239, 25; (b) Davies, H. M. L.; Venkataramani, C.
Org. Lett. 2003, 5, 1403; (c) Espino, C. G.; Fiori, K. W.; Kim, M.;
Du Bois, J. J. Am. Chem. Soc. 2004, 126, 15378; (d) Kitagaki, S.;
Anada, M.; Kataoka, O.; Matsuno, K.; Umeda, C.; Watanabe, N.;
Hashimoto, S. J. Am. Chem. Soc. 1999, 121, 1417.
[14] Wynne, D. C.; Olmstead, M. M.; Jessop, P. G. J. Am. Chem. Soc.
2000, 122, 7638.
[9] (a) Chen, L.; Yang, T.; Cui, H.; Cai, T.; Zhang, L.; Su, C.-Y. J. Mater.
(Lu, Y.)
968
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