Efficient visible light-mediated cross-dehydrogenative coupling reactions of tertiary amines catalyzed by a polymer-immobilized iridium-based photocatalyst

Article abstract of DOI:10.1039/c4gc00058g

The immobilization of an iridium-based heterogeneous photocatalyst via a radical polymerization process is described, and its catalytic activity was evaluated for the aerobic phosphonylation reaction of N-aryl tetrahydroisoquinolines under visible light i

Full text of DOI:10.1039/c4gc00058g

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Efficient visible light-mediated cross-
dehydrogenative coupling reactions of tertiary
amines catalyzed by a polymer-immobilized
iridium-based photocatalyst†
Cite this: Green Chem., 2014, 16,
2438
Received 12th January 2014,
Accepted 5th February 2014
DOI: 10.1039/c4gc00058g
Woo-Jin Yoo and Shū Kobayashi*
www.rsc.org/greenchem
The immobilization of an iridium-based heterogeneous photo- potential of these photoexcited metal chromophores has been
catalyst via a radical polymerization process is described, and its exploited to facilitate the CDC reaction of tertiary amines
catalytic activity was evaluated for the aerobic phosphonylation under ambient conditions in air.6 However, despite their emer-
reaction of N-aryl tetrahydroisoquinolines under visible light gence as efficient catalysts for a wide range of bond formation
irradiation.
processes, the relative cost associated with ruthenium- and
iridium-based photocatalysts limits their practical use. In this
context, the development of easily recoverable and reusable
heterogeneous visible light photocatalysts would be desirable.
However, only limited examples of immobilized ruthenium-
and iridium-based photocatalysts have been reported thus far.7
In this communication, we wish to report a suspension
polymerization protocol to access an immobilized iridium-
based polypyridyl complex, and its evaluation, as a hetero-
geneous visible light photocatalyst, by examining the aerobic
phosphonylation reaction of N-aryl tetrahydroisoquinoline
derivatives.
Based on our interest in the CDC reaction of tertiary
amines,6c,8 and Stephenson’s initial report on the use of an
iridium-based photocatalyst for the oxidative aza-Henry
reactions of N-aryl tetrahydroisoquinolines,6l we targeted
Ir(ppy)2(dtbbpy)PF6 (ppy: 2-phenylpyridyl and dtbbpy: 4,4′-di-
tert-butyl-2,2′-dipyridyl) for immobilization. Our strategy
involved the synthesis of Ir(vppy)2(dtbbpy)PF6 (vppy: 2-(4-vinyl-
phenyl)pyridyl) (1), with the assumption that the introduction
of the aliphatic substituent would not adversely affect the
photocatalytic activity of the immobilized iridium complex
(Scheme 1).
The synthesis of the photoredox active monomer 1 began
with the preparation of 2-(4-vinylphenyl)pyridine via a Suzuki–
Miyaura cross-coupling reaction.9 Following the literature pro-
cedure for the synthesis of Ir(ppy)2(dtbbpy)PF6,10 the desired
polypyridyl iridium complex 1 was obtained, albeit with some
impurities that could not be separated. Despite this setback,
the crude 1 was subjected to the heterogeneous radical
polymerization process, with the understanding that the impu-
rities would not be immobilized, with various well-established
monomeric feedstocks (Scheme 2).
The direct use of carbon–hydrogen (C–H) bonds in cross-coup-
ling reactions is an exciting and challenging area of research
that has the potential to streamline synthetic methods by redu-
cing the amount of materials and energy required to make
complex organic molecules.1 Despite the challenges associated
with the low reactivity and selectivity in C–H bond functionali-
zation, various successful carbon–carbon (C–C) and carbon–
heteroatom (C–X) bond formation reactions have been realized
with C–H bonds as reagents. The cross-dehydrogenative coup-
ling (CDC) reaction of the α-C–H bond of nitrogen atoms
represents one of the most successful examples of mild and
selective C–C and C–X bond formations derived from C–H
bonds.2 Although initial protocols relied heavily upon the use
of stoichiometric amounts of strong oxidants,3 the rapid pro-
gress in this field has led to CDC reactions that can be per-
formed under mild aerobic conditions.4
The use of sunlight, as a renewable and clean source of
energy to facilitate organic transformations, represents a new
frontier for environmentally sustainable organic chemistry.
Recently, ruthenium- and iridium-based polypyridyl com-
plexes, well-known organometallic compounds that absorb
strongly in the visible light spectrum to produce long-lived
photoexcited states, have emerged as efficient catalysts for
organic transformations that are mediated by single-electron
transfer (SET) processes.5 For instance, the strong oxidative
Department of Chemistry, School of Science, The University of Tokyo, Hongo,
Bunkyo-ku, Tokyo 113-0033, Japan. E-mail: shu_kobayashi@chem.s.u-tokyo.ac.jp;
Fax: +81-3-5634-0033; Tel: +81-3-5841-4794
†Electronic supplementary information (ESI) available: General procedures for
the suspension polymerization and the aerobic phosphonylation reaction of
N-aryl tetrahydroisoquinoline derivatives, characterization data (1H NMR, 13C
NMR, 31P NMR, 19F NMR, IR, high-resolution MS) for all new compounds. See
DOI: 10.1039/c4gc00058g
Our initial suspension polymerization protocol was based
on our previously reported conditions,11 with
a small
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Table 1 Evaluation of immobilized visible light photocatalystsa
PS-Ir
3
Monomer
2
Ir loadingb
Yield of
Ir leachingd
(%)
Entry
1
(mmol g−1
)
6ac (%)
3a
3b
0.0590
74
83
1.0
2.1
2
0.0586
0.0523
Scheme 1 Synthesis of monomeric iridium complex
1 based on
Ir(ppy)2(dtbbpy)PF6.
3
3c
90
92
0.9
0.3
4e, f
3d
0.0255
a Reaction conditions: amine 4a (0.25 mmol), phosphite 5a
(0.25 mmol), and PS-Ir 3 (0.0025 mmol, 1 mol%) in MeOH (0.8 mL) at
room temperature for 12 h under a balloon of dry air and 7.1 W white
LED illumination. b Ir levels were determined by inductive coupled
plasma (ICP) analysis of the acid-digested PS-Ir 3. c Yield based on 4a
and determined by 1H NMR analysis using 1,1,2,2-tetrachloroethane as
an internal standard. d Ir levels were determined by ICP analysis of the
crude reaction filtrate. e PS-Ir 3c was subjected to the polymerization
protocol with 2c. f The reaction time was extended to 14 h.
Scheme 2 Immobilization
polymerization.
of
monomer
1
via
suspension
modification with respect to the solvent choice. In general,
these cationic iridium-based photocatalysts are soluble in sol-
vents that are often miscible with water, thus unsuitable for
suspension polymerization. Chlorinated solvents were found
to dissolve 1 well, but inhibited the radical polymerization
reaction. Fortuitously, benzotrifluoride (BTF), known as an
excellent solvent for radical reactions,12 was found to be the
most suitable solvent for our immobilization efforts. With a
polymerization protocol in hand, various monomers were uti-
lized to immobilize 1, and these heterogeneous cross-linked
co-polymers 3 were evaluated as catalysts for the aerobic CDC
reaction of N-phenyl tetrahydroisoquinoline (4a) with diethyl
phosphite (5a) (Table 1).13
We found that the performance of the immobilized photo-
catalysts was affected by the monomer choice for the visible
light-mediated CDC reaction, with the acrylate-based cross-
linked copolymer 3c providing the best results (entries 1–3).
However, when we evaluated the effectiveness of our immobil-
ization strategy, we found that small amounts of iridium leach-
ing occurred. We hypothesized that an additional layer of
polymer might help minimize metal leaching, and when we
subjected 3c to the radical polymerization process with 2c, we
found that the resulting polymer-supported iridium photo-
catalyst 3d was an effective photocatalyst for the aerobic phos-
phonylation reaction with lower levels of iridium leaching
(entry 4).
phosphine oxides 5e–j (Table 2). We initially examined various
N-aryl tetrahydroisoquinolines (4a–e) and found that the sub-
stituents on the aromatic ring influenced the CDC reaction
(entries 1–5). In particular, we found that the strong electron-
donating methoxy group caused the oxidative coupling reac-
tion to become sluggish, and a longer reaction time and a high
catalyst loading were required for complete conversion of 4c
(entry 3). On the other hand, when halogen-substituted tertiary
amines 4d–e were utilized as substrates, side-product for-
mation caused a decrease in the overall yields of the desired
CDC adducts (entries 4 and 5). We then examined various ali-
phatic phosphites 5a–d as nucleophiles, and found that with
the exception of the more bulky diisopropyl phosphite (5d),
the yields of the desired oxidative coupled products were excel-
lent (entries 6–8). We also utilized our immobilized Ir photo-
catalyst 3d for the CDC-type reaction using secondary
phosphine oxides 5e–j as P-based nucleophiles (entries 9–14).
In general, the phosphine oxides were found to be excellent
partners for the aerobic coupling reactions, and good to excel-
lent yields of the expected CDC products were obtained.
Finally, we examined the viability of recovering and reusing
the cross-linked co-polymer 3d for the aerobic phosphonyla-
tion reaction. It was found that the catalyst could be reused at
least four times without a noticeable loss of catalytic activity
with minimal levels of iridium leaching (Scheme 3).
Next, we examined the substrate scope of the visible light-
mediated aerobic CDC reaction of N-aryl tetrahydroisoquino-
lines 4a–e with various phosphites 5a–d and secondary
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Table 2 Substrate scope for the aerobic oxidative coupling reaction
between N-aryl tetrahydroisoquinolines 4a–e with P–H nucleophiles
5a–ja
Table 2 (Contd.)
Yieldb
(%)
Entry Ar
R
Product
Yieldb
(%)
10
11
12
13
14
Ph
Ph
Ph
Ph
Ph
4-Me–C6H4
85
89
87
61
77
Entry Ar
R
Product
1
2
3c
4
5
6
7
Ph
OEt
87
4-MeO–C6H4
4-Cl–C6H4
4-CF3–C6H4
cHexyl
4-Me–C6H4
OEt
97
87
39
47
95
88
4-MeO–C6H4 OEt
4-Br–C6H4
4-Cl–C6H4
Ph
OEt
OEt
a Reaction conditions: amine 4 (0.50 mmol), phosphite/phosphine
oxide 5 (0.50 mmol), and PS-Ir 3d (0.005 mmol, 1 mol%) in MeOH
(1.6 mL) at room temperature for 14 h under a balloon of dry air and
7.1 W white LED illumination. b Yield of isolated product 6 was based
on 4. c Reaction conditions: amine 4c (0.50 mmol), phosphite 5a
(0.50 mmol), and PS-Ir 3d (0.010 mmol, 2 mol%) in MeOH (1.6 mL) at
room temperature for 24 h under a balloon of dry air and 7.1 W white
LED illumination.
OMe
OnBu
Ph
8
9
Ph
Ph
OiPr
67
92
Ph
Scheme 3 Recovery and reuse of PS-Ir 3d.
In conclusion, we successfully immobilized an iridium-
based polypyridyl complex, through the use of the well-estab-
lished suspension polymerization method, and demonstrated
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its effectiveness as a visible light photocatalyst for the aerobic
CDC reaction between N-aryl tetrahydroisoquinolines and
various P–H nucleophiles under visible light irradiation. The
synthetic utility of this heterogeneous photocatalyst was estab-
lished through the recovery and reuse studies, which showed
that the catalyst could be reused up to four times without loss
of reactivity. We anticipate that the immobilization strategy
described in this report could be easily adopted to access mul-
titudes of heterogeneous visible light photocatalysts derived
from metal polypyridyl complexes.
This work was partially supported by a Grant-in-Aid for
Science Research from the Japan Society for the Promotion of
Science (JSPS), the Global COE Program (Chemistry Innovation
through Cooperation of Science and Engineering), The Univer-
sity of Tokyo, the Japan Science and Technology Agency (JST),
and the Ministry of Education, Culture, Sports, Science and
Technology (MEXT), Japan.
B. Chen, C.-H. Tung and L.-Z. Wu, Org. Lett., 2012, 14,
5992; (d) G. Zhang, Y. Ma, S. Wang, Y. Zhang and R. Wang,
J. Am. Chem. Soc., 2012, 134, 12334; (e) E. Boess, C. Schmitz
and M. Klussmann, J. Am. Chem. Soc., 2012, 134, 5317;
(f) E. Boess, D. Sureshkumar, A. Sud, C. Wirtz, C. Farès and
M. Klussmann, J. Am. Chem. Soc., 2011, 133, 8106;
(g) L. Huang, T. Niu, J. Wu and Y. Zhang, J. Org. Chem.,
2011, 76, 1759; (h) O. Baslé, N. Borduas, P. Dubois,
J. M. Chapuzet, T.-H. Chan, J. Lessard and C.-J. Li, Chem.–
Eur. J., 2010, 16, 8162; (i) O. Baslé and C.-J. Li, Chem.
Commun., 2009, 4124; ( j) S.-I. Murahashi, T. Nakae,
H. Terai and N. Komiya, J. Am. Chem. Soc., 2008, 130,
11005; (k) O. Baslé and C.-J. Li, Green Chem., 2007, 9, 1047;
(l) S.-I. Murahashi, N. Komiya, H. Terai and T. Nakae,
J. Am. Chem. Soc., 2003, 125, 15312.
5 For reviews on visible light photocatalysis, please see:
(a) T. P. Yoon, ACS Catal., 2013, 3, 895; (b) Y. Xi, H. Yi and
A. Lei, Org. Biomol. Chem., 2013, 11, 2387; (c) C. K. Prier,
D. A. Rankic and D. W. C. MacMillan, Chem. Rev., 2013,
113, 5322; (d) J. Xuan and W.-J. Xiao, Angew. Chem., Int. Ed.,
2012, 51, 6828; (e) M. A. Ischay and T. P. Yoon, Eur. J. Org.
Chem., 2012, 3359; (f) L. Shi and W. Xia, Chem. Soc. Rev.,
2012, 41, 7687; (g) N. Hoffmann, ChemSusChem, 2012, 5,
352; (h) J. W. Tucker and C. R. J. Stephenson, J. Org. Chem.,
2012, 77, 1617; (i) J. M. R. Narayanam and
C. R. J. Stephenson, Chem. Soc. Rev., 2011, 40, 102;
( j) T. P. Yoon, M. A. Ischay and J. Du, Nat. Chem., 2010, 2,
527.
Notes and references
1 For representative reviews on C–H bond functionalization,
please see: (a) J. Yamaguchi, A. D. Yamaguchi and K. Itami,
Angew. Chem., Int. Ed., 2012, 51, 8960; (b) D. Y.-K. Chen and
S. W. Youn, Chem.–Eur. J., 2012, 18, 9452; (c) S. H. Cho,
J. Y. Kim, J. Kwak and S. Chang, Chem. Soc. Rev., 2011, 40,
5068; (d) C. Liu, H. Zhang, W. Shi and A. Lei, Chem. Rev.,
2011, 111, 1780; (e) C. S. Yeung and V. M. Dong, Chem.
Rev., 2011, 111, 1215.
6 (a) J. Xie, Q. Xue, H. Jin, H. Li, Y. Cheng and C. Zhu, Chem.
Sci., 2013, 4, 1281; (b) X. Ju, D. Li, W. Li, W. Yu and F. Bian,
Adv. Synth. Catal., 2012, 354, 3561; (c) W.-J. Yoo, A. Tanoue
and S. Kobayashi, Chem.–Asian J., 2012, 7, 2764; (d) S. Cai,
X. Zhao, X. Wang, Q. Liu, Z. Li and D. Z. Wang, Angew.
Chem., Int. Ed., 2012, 51, 8050; (e) D. A. DiRocco and
T. Rovis, J. Am. Chem. Soc., 2012, 134, 8094; (f) J. W. Tucker,
Y. Zhang, T. F. Jamison and C. R. J. Stephenson, Angew.
Chem., Int. Ed., 2012, 51, 4144; (g) M. Rueping,
R. M. Koenigs, K. Poscharny, D. C. Fabry, D. Leonori and
C. Vila, Chem.–Eur. J., 2012, 18, 5170; (h) D. B. Freeman,
L. Furst, A. G. Condie and C. R. J. Stephenson, Org. Lett.,
2012, 14, 94; (i) M. Rueping, S. Zhu and R. M. Koenigs,
Chem. Commun., 2011, 47, 12709; ( j) M. Rueping,
D. Leonori and T. Poisson, Chem. Commun., 2011, 47, 9615;
(k) M. Rueping, S. Zhu and R. M. Koenigs, Chem. Commun.,
2011, 47, 8679; (l) A. G. Condie, J. C. González-Gómez and
C. R. J. Stephenson, J. Am. Chem. Soc., 2010, 132, 1464.
7 (a) N. Priyadarshani, Y. Liang, J. Suriboot, H. S. Bazzi and
D. E. Bergbreiter, ACS Macro. Lett., 2013, 2, 571;
(b) C. Wang, K. E. deKrafft and W. Lin, J. Am. Chem. Soc.,
2012, 134, 7211; (c) C. Wang, Z. Xie, K. E. deKrafft and
W. Lin, ACS Appl. Mater. Interfaces, 2012, 4, 2288;
(d) J.-L. Wang, C. Wang, K. E. deKrafft and W. Lin, ACS
Catal., 2012, 2, 417; (e) C. Wang, Z. Xie, K. E. deKrafft and
W. Lin, J. Am. Chem. Soc., 2011, 133, 13445;
(f) H. Shimakoshi, M. Nishi, A. Tanaka, K. Chikama and
Y. Hisaeda, Chem. Commun., 2011, 47, 6548; (g) Z. Xie,
2 For representative reviews on the CDC reactions with ter-
tiary amines, please see: (a) S. A. Girard, T. Knauber and
C.-J. Li, Angew. Chem., Int. Ed., 2014, 53, 74; (b) C. Zhang,
C. Tang and N. Jiao, Chem. Soc. Rev., 2012, 41, 3464;
(c) C. J. Scheuermann, Chem.–Asian J., 2010, 5, 436;
(d) C.-J. Li, Acc. Chem. Res., 2009, 42, 335;
(e) S.-I. Murahashi and D. Zhang, Chem. Soc. Rev., 2008, 37,
1490.
3 (a) T. Nobuta, N. Tada, A. Fujiya, A. Kariya, T. Miura and
A. Itoh, Org. Lett., 2013, 15, 574; (b) L. Huang, X. Zhang and
Y. Zhang, Org. Lett., 2009, 11, 3730; (c) L. Chu, X. Zhang
and F.-L. Qing, Org. Lett., 2009, 11, 2197; (d) C. M. R. Volla
and P. Vogel, Org. Lett., 2009, 11, 1701; (e) X. Xu and X. Li,
Org. Lett., 2009, 11, 1027; (f) O. Baslé and C.-J. Li, Org. Lett.,
2008, 10, 3661; (g) M. Niu, Z. Yin, H. Fu, Y. Jiang and
Y. Zhao, J. Org. Chem., 2008, 73, 3961; (h) Z. Li, D. S. Bohle
and C.-J. Li, Proc. Natl. Acad. Sci. U. S. A., 2006, 103, 8928;
(i) S.-I. Murahashi, N. Komiya and H. Terai, Angew. Chem.,
Int. Ed., 2005, 44, 6931; ( j) Z. Li and C.-J. Li, Eur. J. Org.
Chem., 2005, 3173; (k) Z. Li and C.-J. Li, J. Am. Chem. Soc.,
2005, 127, 6968; (l) Z. Li and C.-J. Li, J. Am. Chem. Soc.,
2005, 127, 3672; (m) Z. Li and C.-J. Li, J. Am. Chem. Soc.,
2004, 126, 11810.
4 (a) M. O. Ratnikov, X. Xu and M. P. Doyle, J. Am. Chem.
Soc., 2013, 135, 9475; (b) J. Dhineshkumar, M. Lamani,
K. Alagiri and K. R. Prabhu, Org. Lett., 2013, 15, 1092;
(c) Q.-Y. Meng, Q. Liu, J.-J. Zhong, H.-H. Zhang, Z.-J. Li,
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C. Wang, K. E. deKrafft and W. Lin, J. Am. Chem. Soc., 2011, 12 (a) J. J. Maul, P. J. Ostrowski, G. A. Ublacker, B. Linclau and
133, 2056.
D. P. Curran, Top. Curr. Chem., 1999, 206, 79; (b) A. Ogawa
and D. P. Curran, J. Org. Chem., 1997, 62, 450.
8 A. Tanoue, W.-J. Yoo and S. Kobayashi, Adv. Synth. Catal.,
2013, 355, 269.
9 H. Mizuno, J. Takaya and N. Iwasawa, J. Am. Chem. Soc.,
2011, 133, 1251.
10 Y. Miyake, K. Nakajima and Y. Nishibayashi, J. Am. Chem.
Soc., 2012, 134, 3338.
11 H. Miyamura, G. C. Y. Choo, T. Yasukawa, W.-J. Yoo and
S. Kobayashi, Chem. Commun., 2013, 49, 9917.
13 Upon a reviewer’s suggestion, we also examined the aerobic
phosphonylation reaction between N-phenyl tetrahydro-
isoquinoline (4a) and diethyl phosphite (5a) using
Ir(ppy)2(dtbbpy)PF6 as a catalyst under our optimized reac-
tion conditions. We found that the reaction proceeds,
albeit with undesired side reactions, to provide the desired
CDC adduct in 55% yield.
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