Letter pubs.acs.org/OrgLett
Visible-Light-Mediated Catalytic Hydroacylation of Dialkyl Azodicarboxylates by Graphite Flakes Giorgos S. Koutoulogenis, Maroula G. Kokotou, Errika Voutyritsa, Dimitris Limnios, and Christoforos G. Kokotos* Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 15771, Greece S Supporting Information *
ABSTRACT: A novel and efficient metal-free catalyzed hydroacylation of dialkyl azodicarboxylates is reported. Graphite flakes were found to be the most efficient catalyst among other carbon-based materials to promote this reaction. This unprecedented catalytic activity can be expanded into a wide substrate scope of aliphatic aldehydes bearing various functional groups, leading to the corresponding products in good to excellent yields.
M
oxidation and hydration of various alcohols and alkynes.7 G.O. has also been reported to promote a carbocatalytic aza-Michael addition of amines to activated alkenes,8 as well as the catalytic ring opening of epoxides.9 Highly selective oxidations of aromatic and aliphatic compounds have been reported,10 as well as arylalkenes in aqueous medium,11 using doped graphene and N-doped sp2-hydridized carbocatalysts, respectively. Lastly, a reductive hydrogen atom transfer was reported by Shi,12 between benzyl alcohols and amines in screening a large library of carbon materials, including graphite flakes,13 however with poor success, while Xu utilized fullerene as the catalyst for the reduction of nitrocompounds.14 Having diverted our attention in photoorganocatalysis, introducing a green and cheap protocol where phenylglyoxylic acid is employed as the photocatalyst to afford not only acyl hydrazides,15a but to promote access to compounds bearing C− N bonds such as amides15b and hydroxamic acids,15c we envisaged the extension of this methodology by employing carbon materials as the catalyst (Scheme 1). We began by investigating the reaction between heptanal 1a with diisopropyl azodicarboxylate 2a with a number of carbon materials, such as graphite flakes, graphene oxide, nanotubes (singlewall, multiwall), and fullerene as the potential catalyst (Table 1). Among the carbon materials tested, the rather inert graphite flakes afforded the best results. This is, to our knowledge, the first successful example of employing cheap graphite flakes as the catalyst.13 The reaction time was set to 2 h, where graphite flakes gave the desired product in a quantitative yield. The excess of the aldehyde was transformed to the corresponding acid, strengthening the hypothesis that an acyl radical is involved. It should be noted that no products deriving from the acyl radical (acyl radicals are known to decompose to CO and
ethodologies that promote C−N bond formation are very important for organic synthesis, since there is a plethora of natural and non-natural bioactive compounds that need quick and simplified methods for their preparation.1 Dialkyl azodicarboxylates are considered good electrophiles due to the combination of their strong electron-withdrawing ability and their unoccupied orbital; therefore, they can be used as intermediates for many substrate conversions.2 Herein, we report that a rather inert and cheap carbon material, such as graphite flakes, can be employed to promote a visible-lightmediated hydroacylation reaction. In recent years, transition metal complexes, such as copper,3 rhenium,4 and tungsten,5 have been reported to catalyze the hydroacylation of dialkyl azodicarboxylates (Scheme 1). Besides the use of metals for the Scheme 1. Photoorganocatalytic and Carbocatalytic Methodologies for the Hydroacylation of Dialkyl Azodicarboxylates
hydroacylation of dialkyl azodicarboxylates, a plethora of methods, such as aerobic activation, pyridine catalysis, and photoorganocatalysis, have been shown to promote this reaction toward acyl hydrazides.6 Although carbon materials have not found an application for the hydroacylation of dialkyl azodicarboxylates, they have been used in promoting other reactions. In 2010, the use of graphene oxide (G.O.) was reported by Bielawski, for the catalytic © XXXX American Chemical Society
Received: February 20, 2017
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DOI: 10.1021/acs.orglett.7b00519 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
decrease of the reaction yield (Table 2, entry 7). However, prolonging the reaction time, led to an increased yield [see Supporting Information (SI)]. One intriguing feature of heterogeneous catalysis with carbon materials is the potential of recycling. However, in most cases, this is not something trivial. Thus, the study of the reaction was followed by the investigation of the recyclability of the material (Table 2). When the material, recovered by a simple filtration, was used for a new reaction mixture, the desired product was isolated in 77% yield (Table 2, entry 8). Unfortunately, the yield dropped in the second and the third recycle. The next step was to explore the boundaries of the substrate scope of this reaction (Scheme 2). Repeating the reaction for
Table 1. Optimization of the Carbon Material and Reaction Conditionsa
entry
material, conditions
NMR yield (%)
1 2 3 4 5 6b 7 8b
graphite flakes graphene oxide nanotubes (singlewall) nanotubes (multiwall) fullerene daylight graphite flakes, dark dark
100 6 81 86 4 6 29 5
Scheme 2. Substrate Scope of the Hydroacylation
a
1a (1.02 mmol), 2a (0.34 mmol), and carbon material (10 mg) in MeCN, under daylight for 2 h at 25 °C. bNo graphite flakes were used.
alkyl radicals) could be detected. After identifying graphite flakes as the optimum material (commercially available and cheap) for this catalytic reaction, we proceeded with the optimization of the reaction conditions, studying the reaction’s performance with and without a catalyst, under daylight and dark conditions (Table 1, entries 1, 6−8). It was found that, under daylight conditions with and without graphite flakes (Table 1, entries 1 and 6), there is a significant difference in the observed yield, which indicates the existence of catalysis by graphite flakes under daylight. Examination under dark reaction conditions (Table 1, entries 7 and 8) showed that graphite flakes require daylight activation, in order to promote the formation of the desired product. Next, the optimization of the solvent was performed (Table 2). MeCN was found to be the best solvent for this catalytic reaction, since it needed only 2 h for the reaction to be completed (Table 2, entry 3). Only EtOAc and toluene followed MeCN’s efficiency in 2.5 and 4 h, respectively. In addition, the mass of the graphite flakes employed was studied. Reducing the amount of the graphite flakes led to a significant Table 2. Optimization of the Reaction Solvent and Examination of the Graphite Flakes’ Recyclabilitya
entry
solvent
time (h)
recycle
NMR yield (%)
1 2 3 4 5 6 7b 8 9 10
EtOAc toluene MeCN H2O MeOH CHCl3 MeCN MeCN MeCN MeCN
2.5 4 2 16 16 9 2 2 2 2
− − − − − − − first second third
100 100 100 100 78 66 30 77 25 14
the synthesis of 3a, we observed that a different reaction time is required for the completion of the reaction depending on the sunlight intensity (summer 2 h vs winter 6 h). Household bulb irradiation provides more consistent results providing the product in 100% yield in 2 h. After using heptanal, we employed butanal which afforded product 3b in 97% yield. We then used α,α-disubstituted aliphatic aldehydes 1c−1e to obtain the corresponding products 3c−3e in 87−100% yield. 2-Ethyl butanal and 3-methyl butanal gave products 3f and 3g in 89% and 94% yield in 3.5 and 16 h, respectively. Cyclohexane− carboxaldehyde afforded product 3h in 92% yield, while product 3i and 3j were isolated in 94% and 59% yield, respectively. Aldehydes bearing a functional group, which are sensitive to radicals, such as citronellal 1k reacted successfully to afford product 3k in 64% yield, while α,β-unsaturated aldehyde 1l afforded product 3l in 57% yield. 3-Phenyl propanal and 5-phenyl pentanal afforded products 3m and 3n
1a (1.02 mmol), 2a (0.34 mmol) and graphite flakes (10 mg) in solvent (3 mL) under daylight at 25 °C. b5 mg of graphite flakes were used. a
B
DOI: 10.1021/acs.orglett.7b00519 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters
(Table 2). Also, the absorption in the UV−vis area of the graphite flakes and the reaction mixture was studied (see SI). The radical nature of the examined reaction was confirmed, when TEMPO or BHT was used as a radical trap and no product was observed, while the presence of the product of the acyl radical with TEMPO and BHT were detected via High Resolution Mass Spectroscopy (HRMS) (Scheme 5). When
in 65% and 78% yield, respectively. Products 3o, 3p, and 3q bearing an ether, an ester, and an amide as functional groups were isolated in 51−61% yield. Aromatic aldehydes afforded products 3r and 3s in moderate yields under compact fluorescent lamp (CFL) irradiation. Except from the corresponding benzoic acid, no decarbonylated products were detected. As mentioned in the introduction, the hydrazine imides obtained from the hydroacylation of diisopropyl azodicarboxylate can be easily converted to a variety of organic compounds bearing a C−N bond.6 With this considered, we synthesized, in a one-pot manner, amide 4 and hydroxamic acid 5 in 45% and 66% yield, respectively (Scheme 3).
Scheme 5. Mechanistic Studies
Scheme 3. Synthesis of Amide 4 and Hydroxamic Acid 5 in a One-Pot Fashion from Heptanal
In our efforts to understand the reaction mechanistic route, we questioned whether the carbon material, after its use throughout this reaction, is subjected to any changes. For this reason, we utilized IR spectroscopy to check the unused graphite flakes, the used graphite flakes at first recycle, and at third recycle, and we noticed some differences (Scheme 4). The
the reaction was run in CD3CN, no deuterium incorporation could be observed, while when heptanal-d1 was employed, full deuterium incorporation in the product was detected (Scheme 5). Thus, the proposed mechanism of the reaction is shown below (Scheme 6). Graphite flakes are activated by daylight or
Scheme 4. IR Spectra of First Recycle, Nonreacted Graphite Flakes, and Third Recycle Following in Order
Scheme 6. Proposed Mechanism of the Hydroacylation of Diisopropyl Azodicarboxylate via Hydrogen Atom Transfer
intensity of the peaks at 1680−1620 cm−1 and at 2950−2850 cm−1, where the alkenyl CC stretch and the alkyl C−H stretch appear, are different in all three cases. The ratio (Intensity C−H: Intensity CC) is low in the unused graphite flakes, and it is at its highest value at the third recycle. This fact indicates that, as time passes by, graphite flakes’ sp2 carbon atoms are decreased, and/or sp3 hybridized C−H carbons are created. This can be explained by the fact that, in order to promote the hydrogen atom transfer required for the hydroacylation, graphite flakes CC are reduced and C−H are created and graphite flakes become nonreactive, explaining the decreased recyclability of graphite flakes as the carbocatalyst
household lamp irradiation to promote a single electron transfer (SET) process, which promotes a hydrogen atom transfer (HAT) from the aldehyde to the graphite flakes to form the first acyl radical. This acyl radical reacts with diisopropyl azodicarboxylate (DIAD) to form radical 6, which commences a radical propagation affording the desired product. Although it is known that CO expulsion is usually preferred leading to alkyl radicals, products derived from these species were not observed. The HAT that takes place each time on the graphite flakes is responsible for the decreased recyclability of graphite flakes, as indicated by IR spectroscopy. Alternatively, the radical propagation could be initiated by the graphene flakes-induced catalytic decomposition of the NN bond of the azodicarboxylate, which can begin the radical chain propagation. In conclusion, an innovative use of graphite flakes as the carbocatalyst for the hydroacylation of diisopropyl azodicarboxC
DOI: 10.1021/acs.orglett.7b00519 Org. Lett. XXXX, XXX, XXX−XXX
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Organic Letters
(8) Verma, S.; Mungse, H. P.; Kumar, N.; Choudhary, S.; Jain, S. L.; Sain, B.; Khatri, O. P. Chem. Commun. 2011, 47, 12673. (9) Dhakshinamoorthy, A.; Alvaro, M.; Concepción, P.; Fornés, V.; Garcia, H. Chem. Commun. 2012, 48, 5443. (10) Dhakshinamoorthy, A.; Primo, A.; Concepción, P.; Alvaro, M.; Garcia, H. Chem. - Eur. J. 2013, 19, 7547. (11) Gao, Y.; Hu, G.; Zhong, J.; Shi, Z.; Zhu, Y.; Su, D. S.; Wang, J.; Bao, X.; Ma, D. Angew. Chem., Int. Ed. 2013, 52, 2109. (12) Yang, H.; Cui, X.; Dai, X.; Deng, Y.; Shi, F. Nat. Commun. 2015, 6, 6478. (13) For an early example of the use of graphite powder for the oxidation of iron salts, see: Kutzelnigg, A. Ber. Dtsch. Chem. Ges. B 1930, 63, 1753. (14) Li, B.; Xu, Z. J. Am. Chem. Soc. 2009, 131, 16380. (15) (a) Papadopoulos, G. N.; Limnios, D.; Kokotos, C. G. Chem. Eur. J. 2014, 20, 13811. (b) Papadopoulos, G. N.; Kokotos, C. G. J. Org. Chem. 2016, 81, 7023. (c) Papadopoulos, G. N.; Kokotos, C. G. Chem. - Eur. J. 2016, 22, 6964.
ylate is reported, affording the desired products in good to excellent yields. Thus, the inert, commercially available, and cheap graphite flakes can be used to promote an organic reaction. Finally, graphite flakes can be filtered after the reaction is completed and be recycled giving the formed acyl hydrazides in lower yields. Application to the one-pot synthesis of amide and hydroxamic acid was also demonstrated. IR spectroscopy showed a chemical modification of the graphite flakes, which causes the decreased recyclability of the material. Further studies are underway in our laboratory.
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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.7b00519. Experimental procedure, full optimization data, characterization data, and NMR spectra (PDF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Christoforos G. Kokotos: 0000-0002-4762-7682 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS The authors would like to thank the Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens for financial support and the Polymer Laboratory for acquiring the IR data. E.V., M.G.K., and D.L. would like to thank the National Scholarship Foundation (IKY) for financial support.
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REFERENCES
(1) For selected reviews and books, see: (a) Vollhardt, K. P. C; Eichberg, M. J. In Strategies and Tactics in Organic Synthesis, Vol. 4; Harmata, M., Ed.; Academic Press: New York, 2004; p 365. (b) Nair, V.; Biju, A. T.; Mathew, S. C.; Babu, B. P. Chem. - Asian J. 2008, 3, 810. (c) Vallribera, A.; Sebastian, R. M.; Shafir, A. Curr. Org. Chem. 2011, 15, 1539. (2) (a) Huisgen, R.; Jakob, F. Liebigs Ann. Chem. 1954, 590, 37. (b) Nair, V.; Menon, A. R. S.; Sreekanth, A. R.; Abhilash, N.; Biju, A. T. Acc. Chem. Res. 2006, 39, 520. (c) Kanzian, T.; Mayr, H. Chem. Eur. J. 2010, 16, 11670. (3) (a) Qin, Y.; Peng, Q.; Song, J.; Zhou, D. Tetrahedron Lett. 2011, 52, 5880. (b) Inamdar, S. M.; More, V. K.; Mandal, S. K. Chem. Lett. 2012, 41, 1484. (4) Lee, D.; Otte, R. D. J. Org. Chem. 2004, 69, 3569. (5) For reviews on decatungstate photocatalysis, see: (a) Tanielian, C. Coord. Chem. Rev. 1998, 178-180, 1165. (b) Tzirakis, M. D.; Lykakis, I. N.; Orfanopoulos, M. Chem. Soc. Rev. 2009, 38, 2609. (6) (a) For a recent review on synthetic approaches towards acyl hydrazides and their uses, see: Shamsabadi, A.; Chudasama, V. Org. Biomol. Chem. 2017, 15, 17. For other contributions, see: (b) Chudasama, V.; Fitzmaurice, R. J.; Caddick, S. Nat. Chem. 2010, 2, 592. (c) Chudasama, V.; Ahern, J. M.; Dhokia, D. V.; Fitzmaurice, R. J.; Caddick, S. Chem. Commun. 2011, 47, 3269. (d) Chudasama, V.; Akhbar, A. R.; Bahou, K. A.; Fitzmaurice, R. J.; Caddick, S. Org. Biomol. Chem. 2013, 11, 7301. (7) Dreyer, D. R.; Jia, H.-P.; Bielawski, C. W. Angew. Chem., Int. Ed. 2010, 49, 6813. D
DOI: 10.1021/acs.orglett.7b00519 Org. Lett. XXXX, XXX, XXX−XXX
