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Nickel-Catalyzed Decarboxylation of Aryl Carbamates for Converting Phenols into Aromatic Amines Akihiro Nishizawa, Tsuyoshi Takahira, Kosuke Yasui, Hayato Fujimoto, Tomohiro Iwai, Masaya Sawamura, Naoto Chatani, and Mamoru Tobisu J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b02751 • Publication Date (Web): 21 Apr 2019 Downloaded from http://pubs.acs.org on April 21, 2019
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Journal of the American Chemical Society
Nickel-Catalyzed Decarboxylation of Aryl Carbamates for Converting Phenols into Aromatic Amines Akihiro Nishizawa,† Tsuyoshi Takahira,† Kosuke Yasui,† Hayato Fujimoto,† Tomohiro Iwai,*,‡ Masaya Sawamura,*,‡, § Naoto Chatani*,† and Mamoru Tobisu*,† †
Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871, Japan Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan §Institute of Chemical Reaction Design and Discovery (WPI-ICReDD), Hokkaido University, Sapporo 060-0810, Japan ‡
Supporting Information Placeholder ABSTRACT: Herein, we describe a new catalytic approach to accessing aromatic amines from an abundant feedstock, namely phenols. The most reliable catalytic method for converting phenols to aromatic amines uses an activating group, such as a trifluoromethane sulfonyl group. However, this activating group is eliminated as a leaving group during the amination process, resulting in significant waste. Our nickel-catalyzed decarboxylation reaction of aryl carbamates forms aromatic amines with carbon dioxide as the only byproduct. As this amination proceeds in the absence of free amines, a range of functionalities, including a formyl group, are compatible. A bisphosphine ligand immobilized on a polystyrene support is key to the success of this reaction, generating a catalytic species that is significantly more active than simple nonsupported variants.
aryl carbamates. Unlike catalytic amination using an activating group, the byproduct is gaseous carbon dioxide (CO2), which is nonflammable, nontoxic, and easily removed from the reaction mixture. Furthermore, the amination proceeds under neutral conditions without using free amines, which allows for complementary functional group compatibility. R1 HN R2 catalyst
(a) RSO2X
OSO2R
HX activated phenol R1 " O " HN X R2 X
Previous method
R N
O
catalyst
R2
O
CO2
aryl carbamate
This Work
(b) R1 N
R1 N
O R2
[Ni] reductive elimination
[Ni] N C
R2
1
HX
Aromatic amines have numerous applications, including in pharmaceuticals, agrochemicals, organic materials, and as ligands for transition metals.1 The catalytic cross-coupling of an aryl halide with an amine, often referred to as the Buchwald–Hartwig amination, has been established as a general and reliable method for the synthesis of aromatic amines.2,3 The use of phenol derivatives instead of aryl halides in the catalytic amination reaction has several advantages, including ready availability from natural sources and unconventional synthetic strategies, such as orthogonal cross-coupling and late-stage functionalization.4–9 Phenols are normally aminated through conversion to the corresponding trifluoromethane sulfonic esters (triflates), which activate the C(aryl)–O bond to undergo the required oxidative addition to the catalyst (Fig. 1a, top). However, this protocol produces stoichiometric fluorinated waste derived from the triflate leaving group. This issue has been partially solved by using nonfluorinated activating groups, such as tosylates,4 mesylates,4,10 sulfamates,4,10 carboxylates,11 carbamates,12,13 and methyl ethers.14 Formal direct amination of phenols was recently reported to proceed using heterogeneous palladium system under hydrogen transfer conditions, in which phenol is temporarily reduced to cyclohexanone derivatives to react with amines15. We envisioned that using the activating groups could be avoided if aryl carbamates, which are readily accessible from phenols and amines, undergo decarboxylation to form C(aryl)–N bonds (Fig. 1a, bottom). However, such catalytic decarboxylative amination reactions have yet to be reported, except for allylic carbamates forming -allylpalladium intermediates.16,17 Herein, we report the first decarboxylative amination of
R1 N
RSO3H
OH
A oxidative addition
[Ni] O
[Ni]
R1
O
2
R
B decarboxylation
R2
O
N 2
R
R1 N
R1 O
R2
O B'
CO2
Figure 1. (a) Previous and current methods for the phenol amination (b) Working mechanism for nickel-catalyzed decarboxylation of aryl carbamates We8 and others4–7,9 have shown that nickel(0) complexes with strong -donor ligands can catalyze various cross-coupling reactions of phenol derivatives that are unreactive with common palladium catalysts. These nickel-catalyzed reactions are initiated by oxidative addition of the C(aryl)–O bond in the phenol derivatives. Accordingly, we postulated that aryl carbamates might undergo decarboxylation when treated with a low-valent nickel catalyst in the absence of any coupling partners via a sequence comprising C(aryl)–O bond oxidative addition, CO2 extrusion, and C(aryl)–N bond-forming reductive elimination (Figure 1b). To examine the feasibility of this hypothesis, the nickel-catalyzed reaction of carbamate 1a was studied in the presence of a series of -donor ligands (Figure 2). Systematic ligand screening identified that 1,2-
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bis(dicyclohexylphosphino)ethane (3b) and N-heterocyclic carbene 3f afforded the expected amination product (2a) in 62% and 36% yields, respectively. However, attempts to increase the yield of 2a further using 3b and 3f failed. We recently reported a new class of polymer-supported phosphine ligand, 3g, which features a rigid 1,2-bis(diphenylphosphino)benzene moiety serving as a four-fold cross-linking unit on a polystyrene support.18 The unique constrained and isolated environment of the bisphosphine motif in 3g allows selective 1:1 complexation of a metal center with the bisphosphine unit and suppresses the undesired comproportionation induced by the encounter of two metal centers. Therefore, using 3g instead of simple nonsupported phosphines led to significantly higher catalytic activity in several metalcatalyzed reactions.18 Furthermore, ligand 3g can be readily synthesized in two steps from commercial reagents. With these results in mind, we next examined ligand 3g for its use in the nickel-catalyzed decarboxylation of 1a. To our delight, using 3g increased the product yield to 94%. In contrast, parent nonsupported ligand 3c was completely inactive, highlighting the enormous impact of catalyst immobilization. It should be noted that 3g alone did not catalyze this decarboxylative amination. The catalyst could be recycled twice without a significant reduction in the yield of 2a (2nd run: 96%; 3rd run: 89%). The loading of Ni(cod)2 and 3g could be reduced to 2.5 or 3 mol% without loss of catalytic activity in the decarboxylation reaction of 1a (77% yield). To date, a common design principle for catalysts that activate inert chemical bonds involves the use of strong -donor ligands. Our results demonstrate that catalyst immobilization offered a conceptually different approach to realizing catalytic reactions that cannot be easily achieved with a simple homogeneous catalyst.
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highlight the advantage of our decarboxylation approach over the existing amination methods in the synthesis of formyl-substituted aniline derivatives (see Supporting Information for details).22
Figure 2. Effect of ligand on nickel-catalyzed decarboxylation of carbamate 1a. NaOtBu (12 mol%) was added, when 3d-f were used. The scope of this decarboxylation of aryl carbamates was next investigated using a Ni(0)/3g catalyst system (Figure 3). Aryl carbamates bearing a variety of functional groups, including ethers (1c), fluorinated substituents (1d and 1e), carbonyl groups (1f-1i, 1p–1z), boronic esters (1k), and heteroarenes (1l–1n) were successfully tolerated in the reaction. Notably, formyl groups (1g, 1h, 1p–1z), which could react with free amines, were also compatible. We were unable to find any other reports on palladiumcatalyzed aminations of aryl halides bearing a formyl group, except for those using less basic anilines19 or fluoroalkylamines.20 In of 4fact, the palladium-catalyzed amination21 bromobenzaldehyde with morpholine was accompanied by amidation of the formyl group. It should be noted that a formyl group was also found to be incompatible with the conditions used for nickel-catalyzed amination of aryl carbamates.12,13 These results
Figure 3. Scope of Nickel-Catalyzed Decarboxylation of Aryl Carbamates. All data are reported as isolated yields. In all cases, the starting carbamates were completely consumed. For details concerning concentration and purification protocol, see the Supporting Information. aNi(cod)2 (20 mol%) and 3g (24 mol%) at 180 °C.
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This decarboxylation also allowed the introduction of a range of amino groups. Aryl carbamates derived from cyclic amines served as excellent substrates, affording corresponding aromatic amines bearing pyrrolidine (2s), piperidine (2q, 2r, and 2u), piperazine (2t), and 1,4-diazepane (2v) ring systems, which are prevalent motifs in medicinal chemistry.23 -Stereocenters (2s) and Boc protecting groups (2t and 2v) were also tolerated. The decarboxylation of aryl carbamates bearing acyclic secondary amine moieties proceeded successfully to give the corresponding aniline derivatives 2w–2z. Although primary amine-derived carbamates failed to undergo decarboxylation under these conditions, using an N-benzyl (2x) protecting group allowed secondary aniline derivatives to be afforded after debenzylation using established methods.24 Diaryl (2y) and triarylamines (2z) were also accessible from the parent carbamates using this catalytic decarboxylation. To obtain mechanistic insights, substituent effects were investigated by comparing the observed rates of decarboxylation reactions using a series of electronically different aryl carbamates. Although we conducted the reactions at 160 °C for the scope and limitation studies, milder conditions (130-140 °C) were employed in the kinetic studies to obtain a clear comparison. The data indicated that the observed rates for the substrates that were examined followed first-order kinetics based on the concentration of the carbamate. Therefore, the effect of substituents was examined by comparison of the rate constants (kobs) for the reaction. The rate for aryl carbamate derived from electron-deficient phenol (i.e., 1g) was higher by 50 times than those derived from the electronneutral phenol (i.e., 1b), which reacted 5 times faster than the electron-rich substrate 1c (Figure 4a). In contrast, the observed rates were less sensitive to the electronic nature of the amine moiety in the aryl carbamate: the krel value was within the range of 0.8~1.1 for aniline derivatives (Figure 4b) and 0.6~0.7 for benzylamine derivatives (Figure 4c). These results suggest that the oxidative addition of the aryl carbamate C(aryl)–O bond (A→B, Figure 1b) is the turnover-limiting step, and not the CO2 extrusion (B→C) or reductive elimination (C→A), in which the electronic effects of the amine moiety would be expected to have a more significant impact.25 Decarboxylation of a mixture of two different aryl carbamates, 1b and 1ag, by Ni(0)/3g catalyst led to the formation of crossover products 2ah and 2ai, and intramolecular amination products 2b and 2ag (Figure 4d). This observation indicated that oxidative addition complex B was in equilibrium with ion pair B’ (Figure 1b). The carbamate anion in B’ can dissociate from the solid support to some extent on heating at 160 °C, which permits anion exchange to occur, eventually leading to the formation of crossover products.26 The decarboxylative C-N bond formation method reported herein allows for the straightforward access to a variety of Narylpiperidines via the three component assembly of phenols, pyridines and organometallic nucleophiles (Figure 5). For example, the aryloxycarbonyl pyridinum 4, which can readily be generated from the corresponding phenol derivative and pyridine, undergoes alkylation (or arylation) at the 4-position using organozinc reagents.27 The subsequent hydrogenation provides the aryl carbamate 1aj, which was successfully decarboxylated to form the N-arylated product 2aj under our Ni(0)/3g catalyst. In this synthetic scheme, the phenol moiety can serve both as an activating group for a pyridine ring and as an arylating reagent. We have developed a nickel-catalyzed decarboxylation reaction of aryl carbamates as a conceptually different protocol for the synthesis of aromatic amines. The required oxidative addition of a C(aryl)-O bond and the extrusion of CO2 were both promoted effectively by the use of nickel(0) complex and a supported
bisphosphine 3g. In addition, decarboxylation strategy allows amination to occur in the absence of free amines, resulting in a wider functional group compatibility. In particular, the tolerance of a formyl group is notable. Although this type of decarboxylation reactions have been limited to allylic and benzylic substrates,16 this work demonstrated the viability of decarboxylation strategy in aromatic systems. We anticipate that a wider range of substrates will be used in decarboxylation reactions28 by developing suitable catalysts, which are the subject of our ongoing studies.
Figure 4. Mechanistic Studies
Figure 5. Synthetic Application
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ASSOCIATED CONTENT
Supporting Information The Supporting Information is available free of charge on the ACS Publications website. Detailed experimental procedures, characterization of new compounds (PDF) AUTHOR INFORMATION
Corresponding Author *
[email protected];
[email protected];
[email protected];
[email protected]; ACKNOWLEDGMENT We thank the Instrumental Analysis Center, Faculty of Engineering, Osaka University, for their assistance with HRMS. This work was supported by JSPS KAKENHI (15H03811 to MT and 17H04877 to TI) and Scientific Research on Innovative Area "Precisely Designed Catalysts with Customized Scaffolding" (18H04259 to MT and 15H05801 to MS) from MEXT, Japan. MT thanks Toray Science Foundation for financial support.
REFERENCES (1) Ruiz-Castillo, P.; Buchwald, S. L., Applications of PalladiumCatalyzed C–N Cross-Coupling Reactions. Chem. Rev. 2016, 116, 1256412649. (2) Surry, D. S.; Buchwald, S. L., Biaryl Phosphane Ligands in PalladiumCatalyzed Amination. Angew. Chem., Int. Ed. 2008, 47, 6338-6361. (3) Hartwig, J. F., Evolution of a Forth Generation Catalyst for the Amination and Thioetherification of Aryl Halides. Acc. Chem. Res. 2008, 41, 1534-1544. (4) Rosen, B. M.; Quasdorf, K. W.; Wilson, D. A.; Zhang, N.; Resmerita, A.-M.; Garg, N. K.; Percec, V., Nickel-Catalyzed Cross-Couplings Involving Carbon−Oxygen Bonds. Chem. Rev. 2011, 111, 1346-1416. (5) Li, B.-J.; Yu, D.-G.; Sun, C.-L.; Shi, Z.-J., Activation of “Inert” Alkenyl/Aryl C–O Bond and Its Application in Cross-Coupling Reactions. Chem.–Eur. J. 2011, 17, 1728-1759. (6) Yamaguchi, J.; Muto, K.; Itami, K., Recent Progress in NickelCatalyzed Biaryl Coupling. Eur. J. Org. Chem. 2013, 2013, 19-30 . (7) Cornella, J.; Zarate, C.; Martin, R., Metal-catalyzed activation of ethers via C–O bond cleavage: a new strategy for molecular diversity Chem. Soc. Rev. 2014, 43, 8081-8097. (8) Tobisu, M.; Chatani, N., Cross-Couplings Using Aryl Ethers via C–O Bond Activation Enabled by Nickel Catalysts. Acc. Chem. Res. 2015, 48, 1717-1726. (9) Zeng, H.; Qiu, Z.; Domínguez-Huerta, A.; Hearne, Z.; Chen, Z.; Li, C.-J., An Adventure in Sustainable Cross-Coupling of Phenols and Derivatives via Carbon–Oxygen Bond Cleavage. ACS Catal. 2017, 7, 510-519. (10) Surry, D. S.; Buchwald, S. L., Dialkylbiaryl phosphines in Pdcatalyzed amination: a user's guide. Chem. Sci. 2011, 2, 27-50. (11) Ramgren, S. D.; Silberstein, A. L.; Yang, Y.; Garg, N. K., NickelCatalyzed Amination of Aryl Sulfamates. Angew. Chem. Int. Ed. 2011, 50, 2171-2173. (12) Shimasaki, T.; Tobisu, M.; Chatani, N., Nickel-Catalyzed Amination of Aryl Pivalates by the Cleavage of Aryl C–O Bonds Angew. Chem. Int. Ed. 2010, 49, 2929-2932. (13) Mesganaw, T.; Silberstein, A. L.; Ramgren, S. D.; Nathel, N. F. F.; Hong, X.; Liu, P.; Garg, N. K., Nickel-catalyzed amination of aryl carbamates and sequential site-selective cross-couplings. Chem. Sci. 2011, 2, 1766-1771. (14) (a) Tobisu, M.; Shimasaki, T.; Chatani, N., Ni0-catalyzed Direct Amination of Anisoles Involving the Cleavage of Carbon-Oxygen Bonds. Chem. Lett. 2009, 38, 710-711. (b) Tobisu, M.; Yasutome, A.; Yamakawa, K.; Shimasaki, T.; Chatani, N., Ni(0)/NHC-catalyzed amination of Nheteroaryl methyl ethers through the cleavage of carbon‒oxygen bonds. Tetrahedron 2012, 68, 5157-5161.
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(15) Chen, Z.; Zeng, H.; Girard, S. A.; Wang, F.; Chen, N.; Li, C.-J., Formal Direct Cross-Coupling of Phenols with Amines. Angew. Chem., Int. Ed. 2015, 54, 14487-14491. (16) Mellegaard-Waetzig, S. R.; Rayabarapu, D. K.; Tunge, J. A., Allylic Amination via Decarboxylative C-N Bond Formation. Synlett 2005, 2005, 2759-2762. (17) The decarboxylative amination of 2-naphthyl carbamate was reported as a side reaction pathway when 100 mol% of a nickel complex was used in the Supporting Information of the following paper: Wang, Y.; Wu, S.B.; Shi, W.-J.; Shi, Z.-J., C–O/C–H Coupling of Polyfluoroarenes with Aryl Carbamates by Cooperative Ni/Cu Catalysis. Org. Lett. 2016, 18, 2548-2551. (18) (a) Iwai, Y.; Harada, T.; Shimada, H.; Asano, K.; Sawamura, M., A Polystyrene-Cross-Linking Bisphosphine: Controlled Metal Monochelation and Ligand-Enabled First-Row Transition Metal Catalysis. ACS Catal. 2017, 7, 1681-1692. (b) Yamazaki, Y.; Arima, N.; Iwai, T.; Sawamura, M. Adv. Synth. Catal. in press, DOI: 10.1002/adsc.201801713. (19) Maiti, D.; Fors, B. P.; Henderson, J. L.; Nakamura, Y.; Buchwald, S. L., Palladium-catalyzed coupling of functionalized primary and secondary amines with aryl and heteroaryl halides: two ligands suffice in most cases. Chem. Sci. 2011, 2, 57-68. (20) Brusoe, A. T.; Hartwig, J. F., Palladium-Catalyzed Arylation of Fluoroalkylamines. J. Am. Chem. Soc. 2015, 137, 8460-8468. (21) Wolfe, J. P.; Buchwald, S. L., Nickel-Catalyzed Amination of Aryl Chlorides. J. Am. Chem. Soc. 1997, 119, 6054-6058. (22) p-NMe2-substituted (S1a) and o-Me-substituted (S1b) carbamates were also applicable to form S2a and S2b, respectively. Alkenyl carbamate S1c was much less reactive under these conditions and the product was formed in only 8%.
(23) Vitaku, E.; Smith, D. T.; Njardarson, J. T., Analysis of the Structural Diversity, Substitution Patterns, and Frequency of Nitrogen Heterocycles among U.S. FDA Approved Pharmaceuticals. J. Med. Chem. 2014, 57, 10257-10274. (24) Adger, B. M.; O'Farrell, C.; Lewis, N. J.; Mitchell, M. B., Catalytic Transfer Hydrogenolysis of N-Benzyl Protecting Groups. Synthesis 1987, 1987, 53-55. (25) Garg reported that the oxidative addition of a C(aryl)-O bond in aryl carbamates is a relatively facile process when a Ni/NHC catalyst is used (ref 13). However, ligand 3g is by far a weaker -donor, thus requiring a higher barrier for the oxidative addition. (26) Another possible mechanism for the formation of crossover products is the generation of a free amine, followed by amination of the aryl carbamate. However, we conclude that this mechanism is unlikely because free amines were not detected during the course of the reaction. The fact that a formyl group is compatible also supports the absence of a free amine during the course of the reaction. (27) Wang, X.; Kauppi, Anna M.; Olsson, R.; Almqvist, F., Efficient Solution-Phase Parallel Synthesis of 4-Substituted N-Protected Piperidines. Eur. J. Org. Chem. 2003, 2003, 4586. (28) (a) Schwarz, J.; König, B., Decarboxylative reactions with and without light – a comparison. Green Chem. 2018, 20, 323-361. (b) Rodríguez, N.; Goossen, L. J., Decarboxylative coupling reactions: a modern strategy for C–C-bond formation. Chem. Soc. Rev. 2011, 40, 5030-5048.
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