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Organoboron Initiated Rh-Catalyzed Asymmetric Cascade Reactions: a Subtle Switch in Regioselectivity Leading to Chiral 3-Benzazepine Derivatives Aurélie Claraz, Fabien Serpier, and Sylvain Darses ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.7b00511 • Publication Date (Web): 07 Apr 2017 Downloaded from http://pubs.acs.org on April 7, 2017
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ACS Catalysis
Organoboron Initiated Rh-Catalyzed Asymmetric Cascade Reactions: a Subtle Switch in Regioselectivity Leading to Chiral 3Benzazepine Derivatives Aurélie Claraz, Fabien Serpier, Sylvain Darses* PSL Research University, Chimie ParisTech - CNRS, Institut de Recherche de Chimie Paris, 11 rue Pierre et Marie Curie, 75005, Paris (France)
Supporting Information Placeholder ABSTRACT: An addition-carbocyclization cascade reac-
tion initiated by arylboronic acids and catalyzed by a rhodium/chiral diene complex is described. Starting from N-bridged yne-enoate derivatives, chiral functionalized 7-membered 3-benzazepine heterocycles were obtained with high enantioselectivities, thanks to a rhodium 1,4-shift.
oselective rhodium-catalyzed arylative cyclization of nitrogen-tethered alkyne-enoate provided chiral pyrrolidines12h (Scheme 1, route 1), where the formation of the 5-membered heterocycle was triggered by the regioselectivity of the alkyne insertion. CO2Me Ph R
[Rh-Ph]
N-Heterocyclic compounds are found in many natural molecules and drugs,1 and are a class of compounds that exhibits interesting biological activities. Among them, the benzazepine framework, a 7-membered azaheterocyclic fused aromatic ring, is the core structural element of many biologically active compounds.2 Despite their interest, methodologies to access benzazepines have been relatively unexplored. Different approaches have been described, including Friedel-Crafts cyclization,3 intramolecular Heck-type reaction or hydroarylation,4 ring enlargement strategies,5 hydroamidation6 and radical cyclization.7 Even if some of these reactions allow the asymmetric synthesis of benzazepine core ring, catalytic asymmetric strategies have been totally unexplored. You et al. have reported the enantioselective synthesis of 1-benzazepines by iridiumcatalyzed tandem allylic vinylation/amination reactions8 and more recently, the group of F. Glorius has described a cooperative N-heterocyclic carbene/palladiumcatalyzed enantioselective umpolung annulation to access to 1-benzazepines.9 Herein we report for the first time a straightforward access to chiral 3-benzazepines via rhodium-catalyzed cascade reaction initiated by organoboron compounds. The rhodium or palladium–catalyzed carbocyclization reactions, initiated by the addition of organoboron reagents,10 represent a powerful approach for the formation of diversely substituted chiral carbo-11 and hetero-cyclic compounds.12 For example, we have shown that enanti-
Ph (1)
N Ts
N Ts Pyrrolidines
R = alkyl
R
CO2Me
[Rh-Ph]
N Ts
R=?
CO2Me
R
[Rh]
CO2Me
[Rh]
Ph
R
New heterocycles ?
(2)
N Ts
Scheme 1. A Switch in the Regioselectivity of Alkyne Insertion Providing New Heterocycles
We envisioned that a reverse alkyne insertion (Scheme 1, route 2) would modify the rhodium-catalyzed cascade process and result in the formation of new heterocycles. In order to switch the regioselectivity of the alkyne insertion, we evaluated the influence of the alkyne substituent13 on the rhodium-catalyzed arylative cyclisation of 1 with phenylboronic acid under our previously reported conditions12h (Table 1). Table 1. From Pyrrolidines to 3-Benzazepines by Reversing the Alkyne Insertiona R
Ph
CO2Me
N Ts
1
PhB(OH)2 (2 equiv) MeOH, 60 °C
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CO2Me
R
[Rh(cod)OH]2 3 mol% CO2Me
R N Ts
2
N Ts
3
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Entry
1, R =
2:3b
Yieldc (%)
1
C6H5 (1a)
79:21
62
2d
C6H5 (1a)
78:22
60
3
SiMe3 (1b)
nre
nre
4
2-pyridyl (1c)
nre
nre
5
4-CF3C6H4 (1d)
91/9
76
6
2-MeC6H4 (1e)
93/7
78
a
The reaction was conducted with 1 (0.15 mmol), phenylboronic acid (0.3 mmol, 2 equiv), [Rh(cod)OH]2 (3 mol % Rh) in degassed methanol at 60 °C. b Determined by 1H NMR of the crude. c Isolated yield of 2. d Using PhBF3K instead of PhB(OH)2. e No reaction.
We were pleased to find that cyclization of 1a, where the alkyne is bearing a phenyl substituent (entry 1), resulted in the formation of a new heterocyclic compound, a 3-benzazepine derivative (2), along with the formation of 20% of pyrrolidine (3). Under identical conditions, the cyclization of 1a in the presence of potassium phenyltrifluoroborate instead of phenylboronic acid (entry 2) does also occur, without any change in the proportion of 2 and 3. Others alkynes substituents were evaluated (entries 3-4),13 like trimethylsilyl, or 2-pyridyl, but the reaction of 1b or 1c did not result in the formation of any heterocycle. On the other hand, the reaction of 1d bearing a 4-trifluoromethylphenyl (entry 5) and even more the reaction of 1e bearing a 2-methylphenyl (entry 6) substituent resulted in the formation of 3-benzazepine 2 with selectivities over than 90%. Indeed, thanks to a change of the alkyne substituent, we could completely change the course of the rhodium-catalyzed arylative cyclization from the formation of pyrrolidines to the formation of 3-benzazepine derivatives. After this successful switch in the regioselective insertion of the alkyne moiety, allowing a straightforward access to 3-benzazepine core structure, we envisioned the development of an enantioselective version of this Rh-catalyzed cascade reaction. After a screening of chiral phosphane and diene ligands (see supporting information), we were pleased to find that cyclization of 1a with 4a in the presence of chiral diene L1*, developed by Hayashi and co-workers,14 furnishes the 3benzazepine 2aa with moderate yield and an enantiomeric excess of 92% (Table 2, entry 1). Gratifyingly, a higher yield, with the same level of enantioselectivity, was obtained from the cyclization of 1e using chiral diene L2*15 (Table 2, entry 2). Table 2. Chiral 3-Benzazepines from Rh/Chiral DieneCatalyzed Arylative Cyclization of 1a
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7
R
CO2Me + N Ts
ArB(OH)2
1
4
[Rh(C 2H 4) 2Cl] 2 3 mol% Ln * 6.6 mol% Dioxane/MeOH 1:1 60 °C
6
9
CO2Me
R
2
R = Ph (1a), R = 2-MeC6H 4 (1e) Ar = C6H 5 (4a), 3-MeC6H 4 (4b), 4-FC6H 4 (4c), 4-BrC6H 4 (4d), 3-BrC6H 4 (4e), 4-ClC6H 4 (4f), 4-CF3OC6H 4 (4g), 4CF3C6H 4 (4h), 4-NO2C6H 4 (4i), 3-Cl-4-FC6H 3 (4j)
X
N Ts
Ln* =
R'
R' = COO(2,6-Me2C6H 3) (L1 *) R' = C(Me)2OH (L 2*)
2
Yieldb (%)
eec (%)
H
2aa
38
92
4a
H
2ea
61
86
1e
4b
7-Me
2eb
84
82
1a
4c
8-F
2ac
36
96
1e
4c
8-F
2ec
70
92
d
1a
4d
8-Br
2ad
44
96
7
1e
4d
8-Br
2ed
75
95
8
1e
4e
7-Br
2ee
59
91
9
1e
4f
8-Cl
2ef
93
95
10
1e
4g
8-CF3O
2eg
87
98
11
1e
4h
8-CF3
2eh
74
97
12
1e
4i
8-NO2
2ei
64
96
13
1e
4j
7-Cl-8-F
2ej
78
97
Entry
1
4
X=
1d
1a
4a
2
1e
3 d
5
4 6
a
The reactions were conducted with 1a or 1e (0.15 mmol), arylboronic acid (0.3 mmol, 2 equiv), in the presence of in situ generated chiral L2*-rhodium complex (6 mol % Rh) in degassed dioxane/methanol 1:1 at 60 °C. b Isolated yields. c Determined by HPLC analysis using a chiral stationary phase (see supporting information). d Using L1* as chiral ligand.
With these reaction conditions in hands, 1a or 1e reacted smoothly with diversely substituted arylboronic acids 4 to afford the corresponding chiral 3benzazepines with moderate to good yields, and with high levels of enantioselectivity ranging from 86 to 98% ee (Table 2). Noteworthy, the best enantioselectivities were obtained from boronic acids containing electronwithdrawing substituents (entries 4-10). With orthosubstituted (2-methylphenylboronic acid) or electronrich (4-methoxyphenylboronic acid) arylboronic acids the reaction was sluggish and the conversion very low. From a general point of view, yields were lower with substrate 1a, due to the formation of pyrrolidine 3. Nevertheless, with alkyne-enoate 1e better yields were generally achieved (from 59 to 93%) as a result of the almost exclusive formation of the 7-membered ring. Under identical conditions, no reaction was observed with substrate 1d, using either L1* or L2*. The structure of 3-benzazepine 2ei was confirmed unambiguously by single-crystal X-ray analysis (Figure 1). The absolute configuration of the stereogenic center of
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2ei was determined to be (S) when L2* was used as ligand. Assuming an analogous reaction pathway, the absolute configuration of the other described 3-benzazepines is supposed to be the same.
CO2Me
R N Ts
[Rh(diene)OR']
MeOH
PhB(OH) 2
R' = H or Me
[Rh]
NO 2
=
[Rh(diene)Ph]
CO2Me
R N Ts
R
CO2Me
CO2Me N Ts N Ts
(S)-2ei
CO2Me
[Rh] H
Figure 1. X-ray Crystal Structure of (S)-2ei
CO2Me
H [Rh] R
N Ts
R
1,4-shift
N Ts
Scheme 3. Proposed Reaction Mechanism In order to get some insight into the reaction mechanism, cyclization of 1e was conducted in the presence of potassium trifluoro(phenyl-d5)borate (Scheme 2). The reaction, conducted in MeOH in the presence of [Rh(cod)OH]2, gave the 3-benzazepine 2ea-d5 in 77% yield, where one of the deuterium atoms on the ortho position of the pentadeuteriophenyl moved to the vinylic position. This 1,4-shift of the deuterium, and thus of the rhodium has yet been observed in transition-metal catalyzed cascade reaction, but not fully exploited for the synthesis of carbocycles or heterocycles.16 D
R
CO2Me [Rh(cod)OH]2 3 mol% N Ts
1e (R = 2-MeC6H4)
C6D5BF3K (2 equiv) MeOH, 60 °C 77%
CO2Me
D
D D R
We next examined the reactivity of the benzazepines, which can further be functionalized thanks to its versatile functional groups such as a methyl ester and an exocyclic double bound. As an illustration, the reactivity of the exocyclic double bound has been studied: the ruthenium catalyzed oxidative cleavage17 of benzazepine (S)2eg gave the corresponding chiral benzazepinone 5 in 71% yield, with no erosion of the enantioselectivity (Scheme 4).
F3CO
D
NTs CO2Me
N Ts
2ea-d5
Scheme 2. Deuterium Labeling Experiment The overall mechanism is believed to involve transmetalation of the arylboron reagent to the in situ generated hydroxorhodium(I) complex followed by regioselective alkyne insertion generating a vinylrhodium intermediate (Scheme 3). Then 1,4-rearrangement occurs to afford an arylrhodium species that undergoes 1,4-addition to the enoate moiety allowing the construction of the 7-membered ring. The resulting rhodium enolate is hydrolyzed by the protic solvent yielding the 3-benzazepine derivatives along with the regeneration of an active alkoxorhodium(I) complex.
CO2Me RuCl3•2H2O (20 mol%) NaIO4 (4 equiv)
F3CO NTs
CH2Cl2/H2O, rt, 36 h
(S)-2eg 98% ee
71%
(S)-5 98% ee
O
Scheme 4. Oxidative Cleavage of the Exocyclic Double Bond In summary, we have developed an efficient atomeconomic cascade reaction for the formation of new chiral 3-benzazepine derivatives with high levels of enantioselectivities. The compounds have been obtained through the first reported example of a rhodiumcatalyzed asymmetric carbocyclization of N-tethered yne-enoate through a high regioselective alkyne insertion and rhodium 1,4-shift. ASSOCIATED CONTENT Experimental procedures, description of the compounds and X-ray diffraction of 2ei. This material is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION Corresponding Author
* E-mail:
[email protected] ACS Paragon Plus Environment
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ACKNOWLEDGMENT Fabien Serpier thanks Diverchim for a grant. The authors warmly thank L.-M. Chamoreau (IPCM, Université Pierre et Marie Curie, Paris) for X-ray analysis.
REFERENCES
1
(a) O’Hagan, D., Nat. Prod. Rep. 2000, 17, 435-446. (b) Majumdar, K. C.; Chattopadhyay, S. K., Heterocycles in Natural Product Synthesis. Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2011. 2 (a) Kametani, T.; Fukumoto, K., Heterocycles 1975, 3, 931-1004. (b) Weinstock, J.; Hieble, J. P.; Wilson, J. W., Drugs Future 1985, 10, 645-697. (c) Gilchrist, T. L. in Heterocyclic Chemistry, 3rd ed., Addison, Wesley, Essex, 1997, pp. 373-383. (d) Kawase, M.; Saito, S.; Motohashi, N., Int. J. Antimicrob. Agents 2000, 14, 193-201. (e) Kouznetsov, V.; Palma, A.; Ewert, C., Curr. Org. Chem. 2001, 5, 519-551. (f) Meigh, J. P. K., Sci. Synth. 2004, 17, 825-927. 3 For selected examples: (a) Damsen, H.; Niggemann, M., Eur. J. Org. Chem. 2015, 7880-7883. (b) So, M.; Kotake, T.; Matsuura, K.; Inui, M.; Kamimura, A., J. Org. Chem. 2012, 77, 4017-4028. (c) Crecente-Campo, J.; Vázquez-Tato, M. P.; Seijas, J. A., Tetrahedron 2009, 65, 2655-2659. (d) Wirt, U.; Schepmann, D.; Wünsch, B., Eur. J. Org. Chem. 2007, 462-475. (e) Padwa, A.; Wang, Q., J. Org. Chem. 2006, 71, 7391-7402. (f) Fuchs, J. R.; Funk, R. L., Org. Lett. 2001, 3, 3349-3351. (g) Gerritz, S. W.; Smith, J. S.; Nanthakumar, S. S.; Uehling, D. E.; Cobb, J. E., Org. Lett. 2000, 2, 4099-4102. 4 (a) Peshkov, A. A.; Peshkov, V. A.; Pereshivko, O. P.; Van Hecke, K.; Kumar, R.; V Van der Eycken, E., J. Org. Chem. 2015, 80, 6598-6608. (b) Wang, L.; Huang, J.; Peng, S.; Liu, H.; Jiang, X.; Wang, J., Angew. Chem. Int. Ed. 2013, 52, 1768-1772. (c) Peshkov, V. A.; Pereshivko, O. P.; Donets, P. A.; Mehta, V. P.; Van der Eycken, E. V., Eur. J. Org. Chem. 2010, 4861-4867. (d) Donets, P. A.; Goeman, J. L.; van der Eycken, J.; Robeyns, K.; Van Meervelt, L.; Van der Eycken, E. V., Eur. J. Org. Chem. 2009, 793-796. (e) Smith, B. M.; Smith, J. M.; Tsai, J. H.; Schultz, J. A.; Gilson, C. A.; Estrada, S. A.; Chen, R. R.; Park, D. M.; Prieto, E. B.; Gallardo, C. S.; Sengupta, D.; Dosa, P. I.; Covel, J. A.; Ren, A.; Webb, R. R.; Beeley, N. R. A.; Martin, M.; Morgan, M.; Espitia, S.; Saldana, H. R.; Bjenning, C.; Whelan, K. T.; Grottick, A. J.; Menzaghi, F.; Thomsen, W. J., J. Med. Chem. 2008, 51, 305-313. (f) Donets, P. A.; Van der Eycken, E. V., Org. Lett. 2007, 9, 3017-3020. (g) Tietze, L. F.; Schimpf, R., Synthesis 1993, 876-880. 5 (a) Gini, A.; Bamberger, J.; Luis-Barrera, J.; Zurro, M.; MasBallesté, R.; Alemán, J.; Mancheño, O. G., Adv. Synth. Catal. 2016, 358, 4049-4056. (b) Gouthami, P.; Chegondi, R.; Chandrasekhar, S., Org. Lett. 2016, 18, 2044-2046. (c) Yu, L.-Z.; Xu, Q.; Tang, X.-Y.; Shi, M., ACS Catal 2016, 6, 526-531. (d) Xiao, T.; Peng, P.; Xie, Y.; Wang, Z.-y.; Zhou, L., Org. Lett. 2015, 17, 4332-4335. (e) Soeta, T.; Ohgai, T.; Sakai, T.; Fujinami, S.; Ukaji, Y., Org. Lett. 2014, 16, 4854-4857. (f) Xiao, T.; Li, L.; Lin, G.; Mao, Z.-w.; Zhou, L., Org. Lett. 2014, 16, 4232-4235. 6 (a) Zhang, L.; Ye, D.; Zhou, Y.; Liu, G.; Feng, E.; Jiang, H.; Liu, H., J. Org. Chem. 2010, 75, 3671-3677. (b) Vieira, T. O.; Alper, H., Org. Lett. 2008, 10, 485-487. 7 (a) Kaoudi, T.; Quiclet-Sire, B.; Seguin, S.; Zard, S. Z., Angew. Chem. Int. Ed. 2000, 39, 731-733. (b) Castedo, L.; Domínguez, D.; Fidalgo, J., Heterocycles 1994, 39, 581-589.
8 (a) Ye, K.-Y.; He, H.; Liu, W.-B.; Dai, L.-X.; Helmchen, G.; You, S.-L., J. Am. Chem. Soc. 2011, 133, 19006-19014. (b) He, H.; Liu, W.-B.; Dai, L.-X.; You, S.-L., Angew. Chem. Int. Ed. 2010, 49, 1496-1499. 9 Guo, C.; Fleige, M.; Janssen-Müller, D.; Daniliuc, C. G.; Glorius, F., J. Am. Chem. Soc. 2016, 138, 7840-7843. 10 For reviews on tandem reaction initiated by organoborons, see: (a) Miura, T.; Murakami, M., Chem. Commun. 2007, 217-224. (b) Youn, S. W., Eur. J. Org. Chem. 2009, 2597-2605. (c) Guo, H.-C.; Ma, J.-A., Angew. Chem. Int. Ed. 2006, 45, 354-366. 11 For some selected examples of formation of chiral carbocyclic compounds using this strategy: (a) Cauble, D. F.; Gipson, J. D.; Krische, M. J., J. Am. Chem. Soc. 2003, 125, 1110-1111. (b) Bocknack, B. M.; Wang, L.-C.; Krische, M. J., Proc. Natl. Acad. Sci. USA 2004, 101, 5421-5424. (c) Shintani, R.; Okamoto, K.; Otomaru, Y.; Ueyama, K.; Hayashi, T., J. Am. Chem. Soc. 2005, 127, 54-55. (d) Shintani, R.; Tsurusaki, A.; Okamoto, K.; Hayashi, T., Angew. Chem. Int. Ed. 2005, 44, 3909-3912. (e) Shintani, R.; Isobe, S.; Takeda, M.; Hayashi, T., Angew. Chem. Int. Ed. 2010, 49, 3795-3798. (f) Shen, K.; Han, X.; Lu, X., Org. Lett. 2012, 14, 1756-1759. (g) Johnson, T.; Choo, K.-L.; Lautens, M., Chem. Eur. J. 2014, 20, 14194-14197. 12 Formation of chiral tetrahydrofurans: (a) Jiang, M.; Jiang, T.; Bäckvall, J.-E., Org. Lett. 2012, 14, 3538-3541. (b) Keilitz, J.; Newman, S. G.; Lautens, M., Org. Lett. 2013, 15, 1148-1151. (c) He, Z.-T.; Tian, B.; Fukui, Y.; Tong, X.; Tian, P.; Lin, G.-Q., Angew. Chem. Int. Ed. 2013, 52, 5314-5318. Formation of chiral dihydrocoumarins: (d) Han, X.; Lu, X., Org. Lett. 2010, 12, 108–111. Formation of chiral hydroxylactones: (e) Song, J.; Shen, Q.; Xu, F.; Lu, X., Org. Lett. 2007, 9, 2947-2950. Formation of chiral N-heterocyclic compounds: (f) Tsukamoto, H.; Matsumoto, T.; Kondo, Y., Org. Lett. 2008, 10, 1047-1050. (g) Li, Y.; Xu, M.-H., Org. Lett. 2014, 16, 2712-2715. (h) Serpier, F.; Flamme, B.; Brayer, J.-L.; Folléas, B.; Darses, S., Org. Lett. 2015, 17, 1720-1723. (i) Serpier, F.; Brayer, J.L.; Folléas, B.; Darses, S., Org. Lett. 2015, 17, 5496-5499. 13 For the regioselective insertion of arylsubstituted alkynes, see: (a) Hayashi, T.; Inoue, K.; Taniguchi, N.; Ogasawara, M., J. Am. Chem. Soc. 2001, 123, 9918-9919. (b) Lautens, M.; Yoshida, M., Org. Lett. 2002, 4, 123-125. (c) Lautens, M.; Yoshida, M., J. Org. Chem. 2003, 68, 762-769. (d) Genin, E.; Michelet, V.; Genet, J.-P., Tetrahedron Lett. 2004, 45, 4157-4161. For the specific case of propargylic amines, see: (e) Arcadi, A.; Aschi, M.; Chiarini, M.; Ferrara, G.; Marinelli, F., Adv. Synth. Catal. 2010, 352, 493-498. (f) Panteleev, J.; Zhang, L.; Lautens, M., Angew. Chem. Int. Ed. 2011, 50, 9089-9092. 14 Okamoto, K.; Hayashi, T.; Rawal, V. H., Chem. Commun. 2009, 4815-4817. 15 Okamoto, K.; Hayashi, T.; Rawal, V. H., Org. Lett. 2008, 10, 4387–4389. 16 For some examples of reactions involving 1,4-shift, see: (a) Hayashi, T.; Inoue, K.; Taniguchi, N.; Ogasawara, M., J. Am. Chem. Soc. 2001, 123, 9918-9919. (b) Miura, T.; Sasaki, T.; Nakazawa, H.; Murakami, M., J. Am. Chem. Soc. 2005, 127, 1390-1391. (c) Shintani, R.; Okamoto, K.; Hayashi, T., J. Am. Chem. Soc. 2005, 127, 28722873. (d) Shintani, R.; Tsurusaki, A.; Okamoto, K.; Hayashi, T., Angew. Chem. Int. Ed. 2005, 44, 3909-3912. (e) Matsuda, T.; Shigeno, M.; Murakami, M., J. Am. Chem. Soc. 2007, 129, 1208612087. (f) Panteleev, J.; Menard, F.; Lautens, M., Adv. Synth. Catal. 2008, 350, 2893-2902. Sasaki, K.; Nishimura, T.; Shintani, R.; Kantchev, E. A. B.; Hayashi, T., Chem. Sci. 2012, 3, 1278-1283 and references cited. 17 Yang, D.; Zhang, C. J. Org. Chem. 2001, 66, 4814.
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R
CO2Me + ArB(OH)2
N Ts
X
[Rh(C 2H 4) 2Cl] 2 3 mol% L* 6.6 mol% Dioxane/MeOH 1:1 60 °C
R' L* =
R N Ts
CO2Me
R' = C(Me)2OH or CO2(2,6-Me 2C6H 3)
up to 98% ee
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