Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Oxidation Potential Tunable Organic Molecules and Their Catalytic Application to Aerobic Dehydrogenation of Tetrahydroquinolines Dahyeon Jung, Seol Heui Jang, Taeeun Yim,* and Jinho Kim* Department of Chemistry and Research Institute of Basic Sciences, Incheon National University, 119 Academy-ro, Yeonsu-gu, Incheon 22012, Republic of Korea
Downloaded via DURHAM UNIV on October 2, 2018 at 14:48:44 (UTC). See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles.
S Supporting Information *
ABSTRACT: In this work, oxidation potential tunable organic molecules, alkyl 2-phenyl hydrazocarboxylates, were disclosed. The exquisite tuning of their oxidation potentials facilitated a catalytic dehydrogenation of 1,2,3,4-tetrahydroquinolines in the presence of Mn(Pc) and O2.
S
pyridine (DMAP).11 However, these redox-active organic molecules exhibited limited redox potentials because the synthesis of their derivatives having various electronic environments was quite restricted. Our continued interest in developing new aerobic oxidative transformations12 has prompted us to investigate the possibility of alky 2-phenyl hydrazocarboxylates as oxidation potential tunable catalysts in aerobic oxidative transformations because of two reasons. First, various alkyl 2-phenyl hydrazocarboxylates having different electronic environments on the aromatic ring could be readily synthesized by the coupling of the corresponding phenylhydrazines with alkyl chloroformates (Scheme 1a).13 We envisioned that the oxidation potentials of alkyl 2-phenyl hydrazocarboxylates were controllable through the variation of the substituents on the phenyl group. Second, the aerobic oxidation of alkyl 2phenyl hydrazocarboxylates was able to be catalyzed by inexpensive metal complexes such as CuI and Fe(Pc) (Pc =
elective oxidative transformations using molecular oxygen are of importance in organic synthesis because molecular oxygen is inexpensive and readily accessible and in many cases produces only water as the byproduct.1 However, the direct oxidation of an organic substrate by O2 is not facile due to the high energy barrier for electron transfer from a singlet organic substrate to triplet molecular oxygen. To circumvent the high energy barrier, catalytic oxidation reactions using a substrateselective catalyst, which may often be a transition metal (Mn+2/ Mn), have been developed.2 The used catalyst oxidizes the organic substrates to the desired products, and the unreactive reduced catalyst is generated. Then, the reduced catalyst is subsequently reoxidized by molecular oxygen for the regeneration of an active catalyst. Sometimes, more than one coupled redox system with electron transfer mediators (ETMs) was required to facilitate the regeneration of the used catalyst by O2.3 Redox-active organic molecules could also be employed as substrate-selective catalysts. Quinones are representative redox-active organic molecules which are used as catalysts in various aerobic oxidative transformations,4 predominantly amine oxidations.5 For example, Wendlandt and Stahl developed bioinspired 1,10-phenanthroline-5,6-dione (phd)catalyzed aerobic oxidation of secondary amines and nitrogencontaining heterocycles.6 Nitroxyl radicals are also employed as substrate-selective catalysts in aerobic alcohol oxidations.7 In the catalytic cycle, oxoammonium salts oxidize organic substrates,8 and the aerobic oxidation of the reduced hydroxyl amines takes place through NOx redox.9,10 Recently, our group has revealed that di-tert-butyl azodicarboxylate (DBAD) was able to catalyze aerobic dehydrogenation of 1,2,3,4-tetrahydroquinolines in the presence of CuI and 4-dimethylamino © XXXX American Chemical Society
Scheme 1. (a) Synthesis of Various Alkyl 2-Phenyl Hydrazocarboxylates and (b) Aerobic Oxidation of Alkyl 2Phenyl Hydrazocarboxylates Catalyzed by Fe(Pc) or Cu
Received: August 28, 2018
A
DOI: 10.1021/acs.orglett.8b02749 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters phthalocyanine) (Scheme 1b).14 Herein, we describe the oxidation potentials of tunable organic molecules and their catalytic application to aerobic dehydrogenation of 1,2,3,4tetrahydroquinolines. To examine our hypothesis, a series of ethyl 2-phenyl hydrazocarboxylates 1 having different substituents at the para position of the phenyl group were synthesized, and their electrochemical oxidation potentials were determined by linear sweep voltammetry (LSV) (Figure 1).15,16 It was revealed that
Table 1. Dehydrogenation of 6-Methyl Tetrahydroquinoline Mediated by Ethyl 2-Phenyl Azocarboxylatesa
yield (%)c entry
R
1 2 3 4 5 6 7 8
OMe Me F H Br CF3 CN NO2
2a 2b 2c 2d 2e 2f 2g 2h
E/V (vs Ag/Ag+)b
σp+
rt
70 °C
0.57 0.68 0.77 0.81 0.84 1.01 1.01 1.00
−0.78 −0.31 −0.07 0.00 0.15 0.61 0.66 0.79
0 1 3 4 11 36 98 100
7 16 34 37 74 99 99 99
a
Reaction conditions: 3a (0.5 mmol) and 2 (1.1 mmol) in CH3CN (1.0 mL) under N2 at room temperature or 70 °C for 12 h. bThe oxidation potentials of the corresponding hydrazocarboxylates were obtained at the highest current. cYield determined by 1H NMR spectroscopy (internal standard: 1,1,2,2-tetrachloroethane).
ethyl 2-(4-nitrophenyl)azocarboxylate 2h, for example, efficiently mediated the dehydrogenation of 3a in a quantitative yield at room temperature (entry 8). These results indicate that the stoichiometric dehydrogenations of 1,2,3,4-tetrahydroquinolines were largely affected by the electrophilicities of the used azo compounds.22 In order to achieve an aerobic dehydrogenation of 1,2,3,4tetrahydroquinolines using catalytic amounts of 2h, several metal phthalocyanine complexes were examined for the aerobic oxidation of ethyl 2-(4-nitrophenyl)hydrazocarboxylate 1h (Table 2). It was observed that Mn(Pc) and Fe(Pc) showed
Figure 1. LSV for various ethyl 2-phenyl hydrazocarboxylates 1 (working electrode: glassy carbon, counter electrode: Pt wire, reference electrode: Ag/Ag+, supporting electrolyte: 0.1 M lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) in CH3CN, scan rate: 100 mV s−1, scan ranges: open-circuit potential to 2.0 V (vs Ag/ Ag+)).
the electrochemical oxidation potentials of 1 strongly depended on the class of substituent: 1 having the more electron-withdrawing substituent showed the higher oxidation potential. Interestingly, approximately linear correlations (r = 0.9834) were observed between the obtained oxidation potentials of 1 and Hammett constants (electrophilic substituent constants, σp+) (Figure 2).17,18 These results indicate that the oxidation potentials of 1 were tunable and predictable on the basis of Hammett constants.19,20
Table 2. Aerobic Oxidation of 2-(4Nitrophenyl)hydrazocarboxylatea
entry
catalyst
yield (%)b
1 2 3 4 5 6 7 8
Mn(Pc) Fe(Pc) Co(Pc) Mn(acac)3 Mn(OAc)2·4H2O MnO2 FeCl3 -
94 93 0 88 0 1 0 0
a
Figure 2. Relationship between oxidation potentials of various 1 and Hammett constants (electrophilic substituent constants, σp+).
Reaction conditions: 1h (0.5 mmol) and catalyst (10 mol %) in CH3CN (1.0 mL) under O2 balloon at room temperature for 12 h. b Yield determined by 1H NMR spectroscopy (internal standard: 1,1,2,2-tetrachloroethane).
Next, we tried to utilize 1 as catalysts in the aerobic dehydrogenations of 1,2,3,4-tetrahydroquinolines. First of all, the reactivity of the ethyl 2-phenyl azocarboxylates 2, which are oxidized forms of 1,14c was investigated in the stoichiometric dehydrogenation of 6-methyl-1,2,3,4-tetrahydroquinoline 3a (Table 1).21 Interestingly, the dehydrogenating activity of 2 highly depended on the substituent of the phenyl group. It was revealed that 2 having the more electron-withdrawing substituent resulted in the higher product yield. The use of
excellent catalytic activity;14b however, Co(Pc) could not catalyze the aerobic oxidation of 1h (entries 1−3). Among the other manganese sources screened, Mn(acac)3 showed a considerable yield, while the aerobic oxidations of 1h using Mn(OAc)2·4H2O or MnO2 were sluggish (entries 4−6). The use of FeCl3 as a catalyst could not catalyze the aerobic oxidation of 1h (entry 7). No autoxidation of 1h was observed for 12 h (entry 8). B
DOI: 10.1021/acs.orglett.8b02749 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
The substrate scope of 1,2,3,4-tetrahydroquinolines using the developed coupled catalytic system (Table 3, entry 7) is elucidated in Scheme 3. Although the aerobic dehydrogen-
We then investigated the cooperation between the dehydrogenation of 1,2,3,4-tetrahydroquinoline mediated by 2h and the aerobic oxidative regeneration of 2h with three potent catalysts including Mn(Pc), Fe(Pc), and Mn(acac)3 (Table 3). Gratifyingly, the coupled catalytic system with 1h,
Scheme 3. Substrate Scope of Aerobic Dehydrogenation of 1,2,3,4-Tetrahydroquinolines Catalyzed by Mn(Pc) and 2(4-Nitrophenyl) Hydrazocarboxylatea
Table 3. Optimization for Dehydrogenation of 6-Methyl Tetrahydroquinoline with Coupled Catalytic Systema
entry
catalyst
hydrazine 1
solvent
temp (°C)
yield (%)b
1 2 3 4 5 6 7 8 9 10c 11 12 13d
Mn(Pc) Fe(Pc) Mn(acac)3 Mn(Pc) Mn(Pc) Mn(Pc) Mn(Pc) Mn(Pc) Mn(Pc) Mn(Pc) Mn(Pc) Mn(Pc)
1h 1h 1h 1h 1h 1h 1h 1f 1g 1h 1h 1h
CH3CN CH3CN CH3CN DMF toluene CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN CH3CN
rt rt rt rt rt 50 70 70 70 70 70 70 70
70 29 40 62 12 79 90 26 52 29 0 6 8
a
Reaction conditions: 3 (0.5 mmol), Mn(Pc) (10 mol %), and 1h (10 mol %) in CH3CN (1.0 mL) under O2 balloon for 15 h. Isolated yield. c Increased amount of 1h was used (30 mol %). dYield determined by 1 H NMR spectroscopy (internal standard: 1,1,2,2-tetrachloroethane)
a
Reaction conditions: 3a (0.5 mmol), catalyst (10 mol %), and 1 (10 mol %) in solvent (1.0 mL) under O2 balloon for 15 h. bYield determined by 1H NMR spectroscopy (internal standard: 1,1,2,2tetrachloroethane). cUnder air. dUnder N2.
ations of 3a and 3b produced the corresponding quinolines in good yield, other tetrahydroquinolines having a methyl group at different positions showed poor results. Increased yields were able to be obtained when increased amounts of hydrazine were used (30 mol %) (4c−4e). Parent quinoline and other 6substitued quinolines were synthesized by the modified reaction conditions in good yields (4f−4i). Various 2-phenyl tetrahydroquinolines were investigated in the developed dehydrogenation. Interestingly, it was revealed that the substituents of the 2-phenyl group affected the reactivity. While 2-phenyl tetrahydroquinolines which have no substituent or electron donating at the para position efficiently underwent the present dehydrogenation (4j−4l), the dehydrogenation of 3m and 3n required increased amounts of 1h to obtain acceptable yields. It was observed that 4-phenyl tetrahydroquinolines, which were synthesized by reductive amination and the sequential cyclization,24 were transformed to the corresponding quinolines in the presence of 30 mol % of 1h (4o−4q). Acridine could be synthesized efficiently by the present aerobic dehydrogenation of 9,10-dihydroacridine (4r). The dehydrogenations of electron-deficient tetrahydroqunolines such as 3s and 3t exhibited poor conversions with good mass balances, even in high loading of 1h (the mass balances of 3s and 3t were 91% and 96%, respectively). In the context of the data in Table 1, these results imply that the electrophilicities of azo compounds and the nucleophilicities of 1,2,3,4-tetrahydroquinolines are crucial in the present dehydrogenation. In conclusion, we revealed that the oxidation potential of ethyl 2-phenyl hydrazocarboxylates could be tunable by the substitution of the phenyl group. The higher oxidation potentials of ethyl 2-phenyl hydrazocarboxylates were observed as stronger electron-withdrawing groups were substituted at the para position of the phenyl ring, and the observed oxidation potentials were highly correlated to Hammett para-
Mn(Pc), and O2 facilitated the dehydrogenation of 1,2,3,4tetrahydroquinoline,23 while both Fe(Pc) and Mn(acac)3 exhibited poor cooperations (entries 1−3). The use of other solvents such as DMF or toluene, instead of CH3CN, did not increase the product yield (entries 4 and 5). The higher yields were obtained as the reaction temperature was increased (entries 6 and 7). The use of 1f or 1g, instead of 1h, as a catalyst produced 4a in 26% or 52% yields, respectively (entries 8 and 9). When the present coupled catalytic system was carried out under air, only 29% of quinoline was produced (entry 10). In order to verify that 2h-mediated dehydrogenation and aerobic regeneration of 2h were conducted independently, control experiments were carried out. Without Mn(Pc), no production of quinoline was observed (entry 11). When the dehydrogenation of 3a was carried out without hydrazine or O2, the poor yields of 4a were observed (entries 12 and 13). These results indicate that no autoxidation of 1h occurred; Mn(Pc)-catalyzed direct oxidation of 3a was sluggish; and molecular oxygen is an essential terminal oxidant. The simplified mechanism proposal for the developed aerobic dehydrogenation of 1,2,3,4-tetrahydroquinoline is depicted in Scheme 2. Scheme 2. Simplified Mechanism Proposal for the Developed Coupled Catalytic System
C
DOI: 10.1021/acs.orglett.8b02749 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
Eldirany, S. A.; Wiberg, K. B.; Bailey, W. F. Org. Lett. 2014, 16, 6484− 6487. (c) Hamlin, T. A.; Kelly, C. B.; Ovian, J. M.; Wiles, R. J.; Tilley, L. J.; Leadbeater, N. E. J. Org. Chem. 2015, 80, 8150−8167. (d) Kelly, C. B.; Lambert, K. M.; Mercadante, M. A.; Ovian, J. M.; Bailey, W. F.; Leadbeater, N. E. Angew. Chem., Int. Ed. 2015, 54, 4241−4245. (e) Kim, M. J.; Mun, J.; Kim, J. Tetrahedron Lett. 2017, 58, 4695− 4698. (f) Kim, M. J.; Kim, J. Bull. Korean Chem. Soc. 2018, 39, 711− 712. (9) For aerobic oxidations catalyzed by 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), see: (a) Liu, R.; Liang, X.; Dong, C.; Hu, X. J. Am. Chem. Soc. 2004, 126, 4112−4113. (b) He, X.; Shen, Z.; Mo, W.; Sun, N.; Hu, B.; Hu, X. Adv. Synth. Catal. 2009, 351, 89−92. (c) Wertz, S.; Studer, A. Adv. Synth. Catal. 2011, 353, 69−72. (d) Prebil, R.; Stavber, G.; Stavber, S. Eur. J. Org. Chem. 2014, 2014, 395−402. (10) For aerobic oxidations catalyzed by less sterically hindered bicyclic nitroxyl radicals, see: (a) Shibuya, M.; Osada, Y.; Sasano, Y.; Tomizawa, M.; Iwabuchi, Y. J. Am. Chem. Soc. 2011, 133, 6497−6500. (b) Kuang, Y.; Nabae, Y.; Hayakawa, T.; Kakimoto, M. Green Chem. 2011, 13, 1659−1663. (c) Lauber, M. B.; Stahl, S. S. ACS Catal. 2013, 3, 2612−2616. (d) Sasano, Y.; Kogure, N.; Nishiyama, T.; Nagasawa, S.; Iwabuchi, Y. Chem. - Asian J. 2015, 10, 1004−1009. (e) Shibuya, M.; Furukawa, K.; Yamamoto, Y. Synlett 2017, 28, 1554−1557. (11) Jung, D.; Kim, M. H.; Kim, J. Org. Lett. 2016, 18, 6300−6303. (12) (a) Noh, J.-H.; Kim, J. J. Org. Chem. 2015, 80, 11624−11628. (b) Yoon, Y.; Kim, B. R.; Lee, C. Y.; Kim, J. Asian J. Org. Chem. 2016, 5, 746−749. (c) Kim, M. J.; Jung, Y. E.; Lee, C. Y.; Kim, J. Tetrahedron Lett. 2018, 59, 2722−2725. (13) Urankar, D.; Steinbü cher, M.; Kosjek, J.; Košmrlj, J. Tetrahedron 2010, 66, 2602−2613. (14) (a) Hirose, D.; Taniguchi, T.; Ishibashi, H. Angew. Chem., Int. Ed. 2013, 52, 4613−4617. (b) Hashimoto, T.; Hirose, D.; Taniguchi, T. Adv. Synth. Catal. 2015, 357, 3346−3352. (c) Kim, M. H.; Kim, J. J. Org. Chem. 2018, 83, 1673−1679. For Pd-catalyzed aerobic oxidation of alkyl 2-phenyl hydrazocarboxylates, see: (d) Gaviraghi, G.; Pinza, M.; Pifferi, G. Synthesis 1981, 1981, 608−610. (15) Jürmann, G.; Tšubrik, O.; Tammeveski, K.; Mäeorg, U. J. Chem. Res. 2005, 2005, 661−662. (16) The oxidation potentials of ethyl 2-phenyl hydrazocarboxylates were obtained at the highest current. The values of oxidation potentials are listed in Table 1. (17) Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165−195. (18) The r values of the correlation between the obtained oxidation potentials of ethyl 2-phenyl hydrazocarboxylates and other Hammett constants such as σp and σp− were shown as 0.9233 and 0.8242. See the Supporting Information for details. (19) For a review for the experimental redox potentials of various organic molecules, see: Warren, J. J.; Tronic, T. A.; Mayer, J. M. Chem. Rev. 2010, 110, 6961−7001. (20) For computational calculation of the substituted quinones, see: Huynh, M. T.; Anson, C. W.; Cavell, A. C.; Stahl, S. S.; HammesSchiffer, S. J. Am. Chem. Soc. 2016, 138, 15903−15910. (21) (a) Stone, M. T. Org. Lett. 2011, 13, 2326−2329. (b) Bang, S. B.; Kim, J. Synth. Commun. 2018, 48, 1291−1298. (22) Kanzian, T.; Mayr, H. Chem. - Eur. J. 2010, 16, 11670−11677. (23) For selected aerobic dehydrogenations of 1,2,3,4-tetrahydroquinoline, see: (a) Furukawa, S.; Suga, A.; Komatsu, T. Chem. Commun. 2014, 50, 3277−3280. (b) Cui, X.; Li, Y.; Bachmann, S.; Scalone, M.; Surkus, A.-E.; Junge, K.; Topf, C.; Beller, M. J. Am. Chem. Soc. 2015, 137, 10652−10658. (c) Iosub, A. V.; Stahl, S. S. Org. Lett. 2015, 17, 4404−4407. (24) Prasada Rao Lingam, V. S.; Thomas, A.; Mukkanti, K.; Gopalan, B. Synth. Commun. 2011, 41, 1809−1828.
substituent constants. From the exquisite tuning of oxidation potentials, we could develop a coupled catalytic system for the aerobic dehydrogenation of 1,2,3,4-tetrahydroquinolines using a Mn(Pc) and 1h redox couple. The control experiments reveal that the catalytic cycles were conducted independently and cooperatively. A variety of 1,2,3,4-tetrahydroquinolines underwent dehydrogenation in the presence of a catalytic amount of Mn(Pc) and 1h to produce the corresponding quinolines. Further studies understanding mechanistic details for each catalytic cycle are underway.
■
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.8b02749. Experimental procedures, spectroscopic data, and copies of 1H and 13C NMR spectra (PDF)
■
AUTHOR INFORMATION
Corresponding Authors
*E-mail:
[email protected] (T. Yim). *E-mail:
[email protected] (J. Kim). ORCID
Taeeun Yim: 0000-0002-7057-9308 Jinho Kim: 0000-0002-3592-9026 Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2018R1A1A1A05019774) and (NRF-2017R1A6A1A06015181).
■
REFERENCES
(1) (a) Stahl, S. S. Angew. Chem., Int. Ed. 2004, 43, 3400−3420. (b) Sigman, M. S.; Jensen, D. R. Acc. Chem. Res. 2006, 39, 221−229. (c) Punniyamurthy, T.; Velusamy, S.; Iqbal, J. Chem. Rev. 2005, 105, 2329−2364. (d) Shi, Z.; Zhang, C.; Tang, C.; Jiao, N. Chem. Soc. Rev. 2012, 41, 3381−3430. (e) Wu, W.; Jiang, H. Acc. Chem. Res. 2012, 45, 1736−1748. (f) Allen, S. E.; Walvoord, R. R.; Padilla-Salinas, R.; Kozlowski, M. C. Chem. Rev. 2013, 113, 6234−6458. (g) Liang, Y.-F.; Jiao, N. Acc. Chem. Res. 2017, 50, 1640−1653. (2) (a) Muthusamy, S.; Kumarswamyreddy, N.; Kesavan, V.; Chandrasekaran, S. Tetrahedron Lett. 2016, 57, 5551−5559. (b) Wang, D.; Weinstein, A. B.; White, P. B.; Stahl, S. S. Chem. Rev. 2018, 118, 2636−2679. (3) Piera, J.; Bäckvall, J.-E. Angew. Chem., Int. Ed. 2008, 47, 3506− 3523. (4) Wendlandt, A. E.; Stahl, S. S. Angew. Chem., Int. Ed. 2015, 54, 14638−14658. (5) (a) Klinman, J. P. J. Biol. Chem. 1996, 271, 27189−27192. (b) Mure, M. Acc. Chem. Res. 2004, 37, 131−139. (6) (a) Wendlandt, A. E.; Stahl, S. S. Org. Lett. 2012, 14, 2850− 2853. (b) Wendlandt, A. E.; Stahl, S. S. J. Am. Chem. Soc. 2014, 136, 506−512. (c) Wendlandt, A. E.; Stahl, S. S. J. Am. Chem. Soc. 2014, 136, 11910−11913. (7) Cao, Q.; Dornan, L. M.; Rogan, L.; Hughes, N. L.; Muldoon, M. J. Chem. Commun. 2014, 50, 4524−4543. (8) For oxoammonium salt-mediated oxidations, see: (a) Bobbitt, J. M.; Bartelson, A. L.; Bailey, W. F.; Hamlin, T. A.; Kelly, C. B. J. Org. Chem. 2014, 79, 1055−1067. (b) Lambert, K. M.; Bobbitt, J. M.; D
DOI: 10.1021/acs.orglett.8b02749 Org. Lett. XXXX, XXX, XXX−XXX
