Letter Cite This: Org. Lett. 2018, 20, 4824−4827
pubs.acs.org/OrgLett
Ru-Photoredox-Catalyzed Decarboxylative Oxygenation of Aliphatic Carboxylic Acids through N‑(acyloxy)phthalimide Chao Zheng,*,†,‡ Yuting Wang,† Yangrui Xu,† Zhen Chen,‡ Guangying Chen,*,† and Steven H. Liang*,‡ †
Org. Lett. 2018.20:4824-4827. Downloaded from pubs.acs.org by ST FRANCIS XAVIER UNIV on 08/17/18. For personal use only.
Key Laboratory of Tropical Medicinal Plant Chemistry of Ministry of Education, Collaborative Innovation Center of Tropical Biological Resources, Hainan Normal University, Hainan Haikou 571158, China ‡ Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, United States S Supporting Information *
ABSTRACT: Decarboxylative aminoxylation of aliphatic carboxylic acid derivatives with (2,2,6,6-tetramethylpiperidin1-yl)oxyl (TEMPO) in the presence of ruthenium photoredox catalysis is reported. The key transformation entails a highly efficient photoredox catalytic cycle using Hantzsch ester as a reductant. The ensuing alkoxyamine can be readily converted to the corresponding alcohol in one pot, representing an alternative approach to access aliphatic alcohols under photoredox conditions.
D
undergo mesolytic cleavage17 by strong oxidative photoredox catalysts, TEMPO is unable to be used in trapping alkyl radicals generated in the reductive quenching process of carboxylate anion with photoredox catalysts (path a in Figure 1). We next conceive that an oxidative quenching process using
ecarboxylative transformations that directly convert readily available and environmentally benign carboxylic acids to various functionalized organic molecules have gained intensive attention in the synthetic community.1 In particular, the rapid development of single-electron redox catalyzed reactions enables a series of challenging and diverse decarboxylative transformations2,3 of aliphatic carboxylates, including decarboxylative arylation,4 alkynylation,5 alkenylation,6 alkylation,7 borylation,8 silylation,9 thiolation,10 selenylation,11 and amination.12 However, a general and practical decarboxylative oxygenation method to convert aliphatic carboxylic acids to the corresponding alcohols has yet to be developed. For example, Lu et al. reported a decarboxylative hydroxylation method using an organophotoredox catalyst and molecular oxygen under irradiation,13 which is most limited to benzylic carboxylic acid substrates and requires an additional functional group manipulation, i.e., reduction with NaBH4/ MeOH to obtain alcohol products due to overoxidation by oxygen. Other literature methods to achieve decarboxylative hydroxylation of aliphatic carboxylic acids include the use of stoichiometric amounts of metal oxidants,14 and Barton esters in the presence of a radical initiator and oxygen under UV light irradiation.15 Furthermore, the use of oxygen under irradiation (e.g., singlet oxygen generated in situ) substantially restricts the practicality and substrate scope. In this context, we consider TEMPO, which is a commonly used reagent in mechanistic studies to probe the existence of radical intermediate,16 but not widely used as coupling reagent in photoredox catalysis, can be a suitable reagent to trap alkyl radicals generated after radical decarboxylation to achieve decarboxylative oxygenation reactions. However, because of the reducing ability of TEMPO [E1/2(TEMPO+/TEMPO) = +0.52 V]16d and the low stability of alkoxyamine products to © 2018 American Chemical Society
Figure 1. Decarboxylative hydroxylation of aliphatic carboxylic acid through aminoxylation with TEMPO.
redox active esters to deliver an alkyl radical may circumvent these problems and form a C−O bond between alkyl radicals and TEMPO (path b in Figure 1). Importantly, a suitable reductant to turn over the photoredox catalyst but not react with TEMPO is crucial to achieve decarboxylative oxygenation reactions. We herein report a ruthenium photoredox catalyst and Hantzsch ester18 system to achieve decarboxylative aminoxylation of aliphatic carboxylic acid-derived N-(acyloxy)phthalimide, followed by the formation of alcohols upon treatment with Zn/HOAc.19 This approach provides a general Received: June 24, 2018 Published: August 2, 2018 4824
DOI: 10.1021/acs.orglett.8b01885 Org. Lett. 2018, 20, 4824−4827
Letter
Organic Letters
10−12). Besides Ru(bpy)3Cl2·6H2O,20 fac-Ir(ppy)3 and organophotoredox catalyst, 4-CzIPN also acted as effective catalysts, albeit to offer lower yields (Table 1, entries 13 and 14). Reductant selection is crucial for this transformation to turn over the photoredox catalyst on the conditions that the reductant should not participate in radical coupling with TEMPO. Thus, various amines and anilines such as DIPEA, Et3N, and N-methyl-N-phenylaniline were all ineffective, as their TEMPO adducts were detectable by GC-MS analysis (Table 1, entries 16−18). We next investigated the substrate scope with aliphatic carboxylic acids (see Scheme 1). Compared with the literature methods,14,15 our method showed broad and diverse substrate compatibility. Benzylic carboxylates, primary, secondary and tertiary aliphatic carboxylates, as well as α-hydroxy acid- and αamine acid-derived esters can be smoothly converted to TEMPO-derived alkoxyamine products in moderate to
and practical method to perform decarboxylative oxygenation/ hydroxylation with excellent chemoselectivity and broad substrate scope using readily available reagents. The optimized reaction conditions are demonstrated in the equation in Table 1. A mixture of N-(cyclohexanecarboxyl)Table 1. Optimized Reaction Conditions of Decarboxylative Oxygenation Reaction
entry
variations from standard conditions
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
none without Ru(bpy)2Cl2·6H2O without Hantzsch ester under air without light Hantzsch ester (0.25 equiv) Hantzsch ester (0.5 equiv) Hantzsch ester (0.75 equiv) Hantzsch ester (1.2 equiv) 1b instead of 1a 1c instead of 1a 1d instead of 1a fac-Ir(ppy)3 instead of Ru(bpy)2Cl2·6H2O 4CzIPN instead of Ru(bpy)2Cl2·6H2O 1-benzyl-4H-pyridine-3-carboxamide instead of Hantzsch ester DIPEAc instead of Hantzsch ester Et3N instead of Hantzsch ester N-methyl-N-phenylaniline instead of Hantzsch ester
16 17 18
yielda (%) 95 (91b) n.r.d n.r. trace n.r. 36 71 84 92 n.r. n.r. n.r. 70 80 n.r.
Scheme 1. Scope of Aliphatic Carboxylic Acids
trace trace trace
a
Reaction conditions: redox-active ester (0.2 mmol), TEMPO (0.3 mmol), photocatalyst (2 mol %), reducing agent (100 mol %) in solvent (2 mL), irradiation by 34 W blue LEDs at room temperature for 24 h under argon atmosphere. Yield determined by 1H NMR using diphenylmethane as an internal standard. bIsolated yield. cDIPEA = diisopropylethylamine.
d
n.r. = no reaction.
phthalimide (0.20 mmol), TEMPO (0.30 mmol), Ru(bpy)3Cl2·6H2O (2.0 mol %), and Hantzsch ester (0.20 mmol) in DMF solvent under an inert atmosphere was irradiated with 34 W blue light-emitting diodes (LEDs) at room temperature. A complete conversion of redox active ester was achieved after 24 h, and the corresponding alkoxyamine product was isolated in 95% yield (Table 1, entry 1). Photoredox catalyst and Hantzsch were essential for this reaction (Table 1, entries 2 and 3). Exposure to air was detrimental (Table 1, entry 4). The reaction did not proceed in the absence of light (Table 1, entry 5). Because one Hantzsch molecule accepts two electrons to turn over the photoredox cycle, the optimal yield was generated using 1.0 equiv of Hantzsch ester (Table 1, entries 6−9). Other types of redox esters were also tested, and only N-(acyloxy)phthalimide was reactive (Table 1, entries
a
Reaction conditions: redox-active esters (0.20 mmol), TEMPO (0.30 mmol), Ru(bpy)3Cl2·6H2O (2.0 mol %), Hantzsch ester (1.0 equiv) in DMF (2.0 mL), irradiation by 34 W blue LEDs at room temperature for 24 h under Ar atmosphere. Yields of isolated products. 4825
DOI: 10.1021/acs.orglett.8b01885 Org. Lett. 2018, 20, 4824−4827
Letter
Organic Letters
product can also be used as an alkyl electrophile to couple with a variety of nucleophiles upon oxidative generation of an alkoxyamine radical cation, followed by mesolytic cleavage.17 The proposed reaction mechanism is shown in Figure 5. After analysis of the redox potential of Ru-photoredox catalyst
excellent yields (52%−96%). Ketones (6, 21), ethers (5, 8), internal alkenes (13), terminal alkenes (18), alkynes (20), and alkyl chlorides (17) were all tolerated. In addition, a phosphine functional group, which is very sensitive to oxidation, was tolerated under our reaction conditions (22). It is worth noting that a few previously inaccessible substrates,13 including primary/secondary aliphatic carboxylic acids, α-hydroxy acids, and α-amino acids, were successfully synthesized by our method. All of the N-acyloxyphthalimides used in Scheme 1 can be easily prepared from corresponding alkyl carboxylic acids in high yield (75%−96%; see the Supporting Information for details). The synthetic utility of our decarboxylative aminoxylation approach was further demonstrated in gram-scale reactions. The scale-up reaction was robust and performed at equal efficiency in a large reaction flask on gram scale (Figure 2).
Figure 5. Plausible mechanism.
[redox potential of Ru(bpy)3Cl2·6H2O: E*1/2II/I = 0.77 V vs SCE, III/II III/ II EII/I 1/2 = −1.33 V vs SCE; E1/2 = 1.29 V vs SCE, E1/2* = −0.81 V vs SCE] and redox active ester (E1/2 = −1.26 to −1.37 V vs SCE), we postulate that the mechanism based on the Ru(III)/ Ru(II) species is less probable, because the redox potential of photoexcited *Ru(II) catalyst is insufficient to reduce NII (acyloxy)phthalimide (EIII/ 1/2* = −0.81 V, compared with E1/2 = −1.26 to −1.37 V vs SCE). In contrast, Ru(I) is suitable to reduce N-(acyloxy)phthalimide due to its strong redox potential (EII/I 1/2 = −1.33 V vs SCE), and photoexcited *Ru(II) is strong enough to oxidize Hantzsch esters (Ered 1/2 = −2.3 V vs SCE).18 Thus, a RuII/RuI redox mechanism is feasible, during which the RuI reduces N-(acyloxy)phthalimide to generate an alkyl radical and a Hantzsch ester reduces the excited *RuII to RuI. The measured quantum yield of the model reaction is 6.7. Since TEMPO trapping alkyl radical is a chain termination process, it is unlikely that radical chain process is involved. The value of quantum yield suggested the concomitance of other energy transfer processes.21 In summary, we have developed a ruthenium photoredoxcatalyzed decarboxylative aminoxylation reaction of aliphatic N-(acyloxy)phthalimide with TEMPO using Hantzsch ester as a reducing agent to turn over photoredox cycle. A broad scope of aliphatic carboxylates, including benzylic, tertiary, secondary, primary, α-amino, and α-hydroxy aliphatic carboxylates, are compatible to provide the corresponding alkoxyamines. The alkoxyamine product can be easily reduced to aliphatic alcohols, thus providing a convenient and practical method for decarboxylative hydroxylation. Attributed to the diverse reactivity of the TEMPO-derived alkoxyamine product as alkyl electrophiles, our method also provides a platform to utilize aliphatic carboxylic acids in organic synthesis.
Figure 2. Gram-scale reactions under optimal conditions.
The N−O bonds of the alkoxyamine products were readily cleaved upon treatment with zinc powder and acetic acid under mild conditions to produce aliphatic alcohols (see Figure 3).19
Figure 3. Reduction of alkoxyamine products to alcohols.
Moreover, it is worth mentioning that the decarboxylative hydroxylation could be performed in one pot in high efficiency without isolating the TEMPO-derived aminoxylation product (Figure 4). Besides, the TEMPO-derived aminoxylation
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ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.8b01885.
Figure 4. One-pot decarboxylative hydroxylation of N-(acyloxy)phthalimide. 4826
DOI: 10.1021/acs.orglett.8b01885 Org. Lett. 2018, 20, 4824−4827
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Organic Letters
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P. S. Nature 2017, 545, 213. (e) Cheng, W.-M.; Shang, R.; Fu, Y. ACS Catal. 2017, 7, 907. (f) Cheng, W.-M.; Shang, R.; Fu, M.-C.; Fu, Y. Chem.Eur. J. 2017, 23, 2537. (5) (a) Yang, J.; Zhang, J.; Qi, L.; Hu, C.; Chen, Y. Chem. Commun. 2015, 51, 5275. (b) Zhang, H.; Zhang, P.; Jiang, M.; Yang, H.; Fu, H. Org. Lett. 2017, 19, 1016. (c) Smith, J. M.; Qin, T.; Merchant, R. R.; Edwards, J. T.; Malins, L. R.; Liu, Z.; Che, G.; Shen, Z.; Shaw, S. A.; Eastgate, M. D.; Baran, P. S. Angew. Chem., Int. Ed. 2017, 56, 11906. (d) Huang, L.; Olivares, A. M.; Weix, D. J. Angew. Chem., Int. Ed. 2017, 56, 11901. (6) (a) Zhang, J.-J.; Yang, J.-C.; Guo, L.-N.; Duan, X.-H. Chem. Eur. J. 2017, 23, 10259. (b) Xu, K.; Tan, Z.; Zhang, H.; Liu, J.; Zhang, S.; Wang, Z. Chem. Commun. 2017, 53, 10719. (c) Wang, G.-Z.; Shang, R.; Fu, Y. Org. Lett. 2018, 20, 888. (7) (a) Schnermann, M. J.; Overman, L. E. J. Am. Chem. Soc. 2011, 133, 16425. (b) Lackner, G. L.; Quasdorf, K. W.; Overman, L. E. J. Am. Chem. Soc. 2013, 135, 15342. (c) Jamison, C. R.; Overman, L. E. Acc. Chem. Res. 2016, 49, 1578. (d) Qin, T.; Cornella, J.; Li, C.; Malins, L. R.; Edwards, J. T.; Kawamura, S.; Maxwell, B. D.; Eastgate, M. D.; Baran, P. S. Science 2016, 352, 801. (e) Lu, X.; Xiao, B.; Liu, L.; Fu, Y. Chem.Eur. J. 2016, 22, 11161. (f) Zhao, Y.; Chen, J.-R.; Xiao, W.-J. Org. Lett. 2018, 20, 224. (g) Kong, W.; Yu, C.; An, H.; Song, Q. Org. Lett. 2018, 20, 349. (8) (a) Hu, D.; Wang, L.; Li, P. Org. Lett. 2017, 19, 2770. (b) Candish, L.; Teders, M.; Glorius, F. J. Am. Chem. Soc. 2017, 139, 7440. (c) Fawcett, A.; Pradeilles, J.; Wang, Y.; Mutsuga, T.; Myers, E. L.; Aggarwal, V. K. Science 2017, 357, 283. (d) Cheng, W.-M.; Zhao, B.; Xing, W.-L.; Shang, R.; Fu, Y. Org. Lett. 2017, 19, 4291. (e) Li, C.; Wang, J.; Barton, L. M.; Yu, S.; Tian, M.; Peters, D. S.; Kumar, M.; Yu, A. W.; Johnson, K. A.; Chatterjee, A. K.; Yan, M.; Baran, P. S. Science 2017, 356, eaam7355. (9) Xue, W.; Oestreich, M. Angew. Chem., Int. Ed. 2017, 56, 11649. (10) Jin, Y.; Yang, H.; Fu, H. Chem. Commun. 2016, 52, 12909. (11) Jiang, M.; Yang, H.; Fu, H. Org. Lett. 2016, 18, 1968. (12) Mao, R.; Frey, A.; Balon, J.; Hu, X. Nature Catal. 2018, 1, 120. (13) Song, H.-T.; Ding, W.; Zhou, Q.-Q.; Liu, J.; Lu, L.-Q.; Xiao, W.-J. J. Org. Chem. 2016, 81, 7250. (14) (a) Corey, E. J.; Casanova, J. J. Am. Chem. Soc. 1963, 85, 165. (b) Kochi, J. K.; Bacha, J. D.; Bethea, T. W. J. Am. Chem. Soc. 1967, 89, 6538. (c) Anderson, J. M.; Kochi, J. K. J. Am. Chem. Soc. 1970, 92, 2450. (d) Feng, Q.; Song, Q. J. Org. Chem. 2014, 79, 1867. (15) (a) Crich, D.; Quintero, L. Chem. Rev. 1989, 89, 1413. (b) Asaba, T.; Katoh, Y.; Urabe, D.; Inoue, M. Angew. Chem., Int. Ed. 2015, 54, 14457. (16) (a) Vogler, T.; Studer, A. Synthesis 2008, 13, 1979. (b) Hartmann, M.; Li, Y.; Studer, A. J. Am. Chem. Soc. 2012, 134, 16516. (c) Wang, G.-Z.; Shang, R.; Fu, Y. Synthesis 2018, 50, 2908. (d) Hodgson, J. L.; Namazian, M.; Bottle, S. E.; Coote, M. L. J. Phys. Chem. A 2007, 111, 13595. (17) Zhu, Q.-L.; Gentry, E. C.; Knowles, R. R. Angew. Chem., Int. Ed. 2016, 55, 9969. (18) Huang, W.; Cheng, X. Synlett 2017, 28, 148. (19) (a) Jahn, E.; Smrček, J.; Pohl, R.; Císařová, I.; Jones, P.; Jahn, U. Eur. J. Org. Chem. 2015, 2015, 7785. (b) Deng, X.; Liang, K.; Tong, X.; Ding, M.; Li, D.; Xia, C. Org. Lett. 2014, 16, 3276. (c) Xu, F.; Zhu, L.; Zhu, S.; Yan, X.; Xu, H.-C. Chem.Eur. J. 2014, 20, 12740. (d) Schultz, A.; Dai, M.; Tham, F.; Zhang, X. Tetrahedron Lett. 1998, 39, 6663. (e) Hartmann, M.; Li, Y.; Studer, A. J. Am. Chem. Soc. 2012, 134, 16516. (20) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 2013, 113, 5322. (21) Cismesia, M. A.; Yoon, T. P. Chem. Sci. 2015, 6, 5426.
Experimental details and characterization data for all products (PDF)
AUTHOR INFORMATION
Corresponding Authors
*E-mail:
[email protected] *E-mail:
[email protected] *E-mail:
[email protected] ORCID
Chao Zheng: 0000-0002-2179-8096 Zhen Chen: 0000-0002-6289-4332 Steven H. Liang: 0000-0003-1413-6315 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This research was funded by the National Natural Science Foundation of China (NSFC) (Grant No. 21702039), the Program for Innovative Research Team in University (No. IRT-16R19), and Hainan Province Natural Science Foundation of Innovative Research Team Project (No. 2016CXTD007). S.H.L. is thankful for the general support from the Department of Radiology, MGH and Harvard Medical School.
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REFERENCES
(1) (a) Goossen, L. J.; Deng, G.; Levy, L. M. Science 2006, 313, 662. (b) Shang, R.; Fu, Y.; Li, J.-B.; Zhang, S.-L.; Guo, Q.-X.; Liu, L. J. Am. Chem. Soc. 2009, 131, 5738. (c) Shang, R.; Fu, Y.; Wang, Y.; Xu, Q.; Yu, H.-Z.; Liu, L. Angew. Chem., Int. Ed. 2009, 48, 9350. (d) Shang, R.; Yang, Z.-W.; Wang, Y.; Zhang, S.-L.; Liu, L. J. Am. Chem. Soc. 2010, 132, 14391. (e) Rodríguez, N.; Goossen, L. J. Chem. Soc. Rev. 2011, 40, 5030. (f) Shang, R.; Ji, D.-S.; Chu, L.; Fu, Y.; Liu, L. Angew. Chem., Int. Ed. 2011, 50, 4470. (g) Shang, R.; Liu, L. Sci. China: Chem. 2011, 54, 1670. (h) Wang, G.-Z.; Shang, R.; Cheng, W.-M.; Fu, Y. Org. Lett. 2015, 17, 4830. (i) Johnston, C. P.; Smith, R. T.; Allmendinger, S.; MacMillan, D. W. C. Nature 2016, 536, 322. (j) Wei, Y.; Hu, P.; Zhang, M.; Su, W. Chem. Rev. 2017, 117, 8864. (2) (a) Nefkens, G. H. L.; Tesser, G. I. J. Am. Chem. Soc. 1961, 83, 1263. (b) Xuan, J.; Zhang, Z. G.; Xiao, W.-J. Angew. Chem., Int. Ed. 2015, 54, 15632. (c) Murarka, S. Adv. Synth. Catal. 2018, 360, 1735. (d) Chen, L.; Chao, C. S.; Pan, Y.; Dong, S.; Teo, Y. C.; Wang, J.; Tan, C.-H. Org. Biomol. Chem. 2013, 11, 5922. (e) Xie, J.; Xu, P.; Li, H.; Xue, Q.; Jin, H.; Cheng, Y.; Zhu, C. Chem. Commun. 2013, 49, 5672. (f) Miyake, Y.; Nakajima, K.; Nishibayashi, Y. Chem. Commun. 2013, 49, 7854. (g) Zuo, Z.; Ahneman, D. T.; Chu, L.; Terrett, J. A.; Doyle, A. G.; MacMillan, D. W. C. Science 2014, 345, 437. (3) (a) Okada, K.; Okamoto, K.; Oda, M. J. Am. Chem. Soc. 1988, 110, 8736. (b) Gallezot, P. Chem. Soc. Rev. 2012, 41, 1538. (c) Straathof, A. J. J. Chem. Rev. 2014, 114, 1871. (d) Zhou, Q.-Q.; Guo, W.; Ding, W.; Wu, X.; Chen, X.; Lu, L.-Q.; Xiao, W.-J. Angew. Chem., Int. Ed. 2015, 54, 11196. (e) Le Vaillant, F.; Courant, T.; Waser, J. Angew. Chem., Int. Ed. 2015, 54, 11200. (f) Schwarz, J.; König, B. Green Chem. 2018, 20, 323. (4) (a) Cornella, J.; Edwards, J. T.; Qin, T.; Kawamura, S.; Wang, J.; Pan, C.-M.; Gianatassio, R.; Schmidt, M.; Eastgate, M. D.; Baran, P. S. J. Am. Chem. Soc. 2016, 138, 2174. (b) Huihui, K. M. M.; Caputo, J. A.; Melchor, Z.; Olivares, A. M.; Spiewak, A. M.; Johnson, K. A.; DiBenedetto, T. A.; Kim, S.; Ackerman, L. K. G.; Weix, D. J. J. Am. Chem. Soc. 2016, 138, 5016. (c) Toriyama, F.; Cornella, J.; Wimmer, L.; Chen, T.-G.; Dixon, D. D.; Creech, G.; Baran, P. S. J. Am. Chem. Soc. 2016, 138, 11132. (d) Edwards, J. T.; Merchant, R. R.; McClymont, K. S.; Knouse, K. W.; Qin, T.; Malins, L. R.; Vokits, B.; Shaw, S. A.; Bao, D.-H.; Wei, F.-L.; Zhou, T.; Eastgate, M. D.; Baran, 4827
DOI: 10.1021/acs.orglett.8b01885 Org. Lett. 2018, 20, 4824−4827
