Letter pubs.acs.org/OrgLett
Iodine(III)-Catalyzed Formal [2 + 2 + 1] Cycloaddition Reaction for Metal-Free Construction of Oxazoles Takuma Yagyu,† Yusuke Takemoto,† Akira Yoshimura,‡ Viktor V. Zhdankin,‡ and Akio Saito*,† †
Division of Applied Chemistry, Institute of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan, and ‡ Department of Chemistry and Biochemistry, University of Minnesota, Duluth, Minnesota 55812 United States S Supporting Information *
ABSTRACT: The iodine(III) catalyst, in situ generated from iodoarene as a precatalyst with m-CPBA and Tf2NH, promoted the metal-free [2 + 2 + 1] cycloaddition-type reactions of alkynes, nitriles, and oxygen atoms for the regioselective formations of 2,4-disubstituted and 2,4,5trisubstituted oxazole. A first example of iodine catalysis for multicomponent reactions is represented.
M
chemistry and synthetic chemistry.4 These procedures are regarded as complementary methods: one is gold-catalyzed preparations of 2,5-disubstituted oxazoles from terminal alkynes,3a and another is Cu-catalyzed preparations of 2,4,5trisubstituted oxazoles from internal alkynes.3b However, these [2 + 2 + 1] cycloaddition strategies cannot be applied to both terminal and internal alkynes. Although other multicomponent cycloaddition-type approaches to oxazoles are also known,5 the formation of 2,4-disubstituted oxazoles has not been achieved by these procedures.6 On the other hand, as part of our studies on the metal-free synthesis of aromatic heterocycles through the activation of alkynes by hypervalent iodine(III) reagents,7 we have recently found the regioselective [2 + 2 + 1] cycloaddition-type reactions of alkynes, nitriles, and oxygen atom from PhI(OH)X (Scheme 1b), which was in situ generated from iodosylbenzene and HX (X = TfO or Tf2N, Tf = CF3SO2).7a However, despite providing the formation not only of 2,4-disubstituted oxazoles but also of 2,4,5-trisubstituted ones, these reactions release a large amount of PhI as a waste product and/or require additional steps for the preparation and purification of iodosylbenzene. From the viewpoint of atom- and stepeconomy, hypervalent iodine(III) catalysts,8 which are generated from ArI precatalysts and terminal oxidants (mainly, m-chloroperbenzoic acid: mCPBA), have been employed in bimolecular oxidative annulations for oxazoles9 and other heterocycle synthesis.10 However, iodine catalysis for multicomponent reactions has not been achieved. Herein, we report a metal-free and regioselective [2 + 2 + 1]-type synthesis of oxazoles based on the iodine(III) catalysis (Scheme 1 c). Our initial effort was focused on the evaluation of ArI precatalysts (20 mol %) with mCPBA and Tf2NH (1.5 equiv each) in the reaction of ethynylbenzene (1a) and acetonitrile
ulticomponent cycloaddition reactions, which allow for multiple bond formation in a single operation, can provide more atom-, step-, and time-economical conversion of simple starting materials to complex and polyfunctionalized cyclic compounds.1 Based on these reactions, mild and efficient approaches to substituted pyridines, furans, pyrroles, and some important azoles using heteroatom-containing unsaturated compounds as starting materials in the presence of various metal catalysts have been developed.2 Recently, Zhang’s and Jiang’s groups independently reported catalytic and regioselective [2 + 2 + 1] cycloaddition-type reactions of alkynes, nitriles, and oxygen atom as facile and efficient assembling procedures of highly substituted oxazoles (Scheme 1a),3 which have found widespread applications in the fields of medicinal Scheme 1. [2 + 2 + 1]-Type Synthesis of Oxazoles
Received: March 12, 2017 Published: May 4, 2017 © 2017 American Chemical Society
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DOI: 10.1021/acs.orglett.7b00742 Org. Lett. 2017, 19, 2506−2509
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Organic Letters (MeCN) as a solvent at ambient temperature for 24 h (Table 1). Note that mCPBA was dried in vacuo prior to use because
Table 2. Reaction Scope of Alkynes and Nitriles
Table 1. Evaluation of ArI Precatalysts
product yielda (%) entry
ArI
yielda (%)
1 2 3 4 5 6 7 8 9 10 11 12 13 14f
PhI 2-ClC6H4I 3-ClC6H4I 4-ClC6H4I 2-IC6H4I 3-NO2C6H4I 4-MeC6H4I 2,4-Me2C6H3I 2,6-(MeO)2C6H3I 2,2′-diiodobipenylc PhIc PhId none PhI
61b 52 37 58b 34 52 43 42 49 41 57 46 7e 30
a
Yields were determined by 1H NMR analysis, unless stated otherwise. Isolated yields. c10 mol %. d5 mol %. e2,4-Dimethyl-6-phenylpyrimidine: 30% (5−16% in other cases). fIn the presence of 20 equiv of MeCN, CH2Cl2 was used as a solvent (CH2Cl2:MeCN = ca. 4:1). b
entry
1
R1
R2
1 2 3 4 5 6 7 8c 9c 10c 11 12 13 14 15 16
1a 1b 1c 1d 1e 1f 1g 1h 1i 1j 1a 1d 1a 1d 1a 1d
Ph (CH2)2Ph (CH2)5Me Ph Ph Pr Ph Ph (CH2)5Me Ph Ph Ph Ph Ph Ph Ph
H H H Me Ph Pr Br Bz Bz Ac H Me H Me H Me
2a 2b 2c 2d 2e 2f 2g 2h 2i 2j 3a 3d 4a 4d 5a 5d
A
B
Cb
61 72 47 63 75 35 37 44 24 44 47 60 58 69 24 59
58 74 50 60 81 36 28 60 45 54 39 57 40 68 26 66
60 80 52 70 73 64 42 70 NE 68 57 76 NE NE 40 52
a c
Isolated yields. bYields found in the ref 7a. NE: not examined. Tf2NH: 3 equiv.
conditions B showed good results (2h,i: 45−60%, entries 8− 10). Propionitrile and isobutyronitrile instead of acetonitrile reacted well with terminal and internal alkynes 1a and 1d under conditions A (3, 4: 47−69%, entries 11−14), and benzonitrile did well with 1a and 1d under conditions B (5a: 26%, 5d: 66%, entries 15, 16). Notably, in all cases, products 2−5 were obtained with complete regioselectivities. Except for aliphatic internal alkyne 1f, catalytic conditions A and/or B brought about nearly the same results as conditions C. In order to gain additional information on the present catalytic cycle for the [2 + 2 + 1]-type synthesis of oxazoles, we attempted the isolation of iodine(III) species generated from PhI, mCPBA, and Tf2NH. PhI was treated with mCPBA and Tf2NH (1.1 equiv each) in the presence of 18-crown-6 ether (18C6) at −40 to 0 °C for 4 h to give PhI(OH)NTf2 as an aquo-[18C6] complex 6 in 43% yield (Scheme 2), although
the use of commercially available mCPBA (contains ca. 30% water) or the positive addition of water brought about the reduced yield of desired products (see the Supporting Information for details of condition optimization). At the outset, the use of PhI as a precatalyst was found to produce the 2,4-disubstituted oxazole 2a in 61% yield as a sole regioisomer (entry 1). On the other hand, although 4-ClC6H4I led to a relatively good yield of 2a (58%, entry 4), ArI having electronwithdrawing groups such as halogens and a nitro group gave reduced yields of 2a (34−52%, entries 2, 3, 5, and 6). Also, in the case of ArI having electron-donating groups, 2a was obtained in 42−49% yield (entries 7−9). Furthermore, bisiodine(III) catalysts, which showed superior results to monoiodine(III) catalysts in some cases,11 did not bring about improved yields of 2a (entries 5 and 10). Unfortunately, when the catalytic amount (10 or 5 mol %, entry 11 or 12) of PhI or the amount of MeCN (20 equiv in CH2Cl2, entry 14) was decreased, the yield of 1a was reduced. It should be mentioned that no addition of ArI afforded 2,4-dimethyl-6phenylpyrimidine, generated from 2a and MeCN under acidic conditions,12 as a main product (entry 13). Based on the above results, we next investigated the scope of alkynes and nitriles under conditions A using PhI or B using 4ClC6H4I with mCPBA and Tf2NH (1.5 equiv each, Table 2). In addition, our previous procedure utilizing iodosylbenzene (1.8 equiv) with Tf2NH (1.5 equiv) is shown as conditions C in Table 2.7a Both catalytic conditions A and B were successfully applied to the oxidative annulations of not only terminal alkynes 1a−c but also internal alkynes 1d−g with acetonitrile to give the corresponding 2,4-disubstituted or 2,4,5-trisubstituted oxazoles 2a−g in 28−81% yields (entries 1−7). In the cases of 1h−j bearing electron-withdrawing groups such as benzoyl and acetyl groups, the addition of 3 equiv of Tf2NH under
Scheme 2. Iodine(III) Species Generated from PhI, mCPBA, and Tf2NH
iodine(III) species could not be isolated in the absence of 18C6. Miyamoto et al. reported that complex 6 was generated from PhI(OAc)2 and Tf2NH in the presence of 18C6.13 These observations suggest that m-chlorobenzoic acid (mCBA) as a byproduct would not be involved in the present catalytic cycle. This conclusion is supported by the fact that, regardless of the addition of mCBA, iodosylbenzene with Tf2NH (conditions C) 2507
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Organic Letters afforded oxazole 2a in the same yields from 1a and acetonitrile (Scheme 3).
alkynes and some iodine(III) reagents,15 the deuterium-labeling experiment using d-1a (Scheme 5) suggests the negative
Scheme 3. Control Experiments
Scheme 5. Deuterium-Labeling Experiment
On the basis of these results and our previous reports about the PhIO/acid-mediated [2 + 2 + 1]-type synthesis of oxazoles, the proposed catalytic cycle for the present [2 + 2 + 1] cycloaddition-type reaction is shown in Scheme 4. That is,
involvement of intermediate H in the present oxazole formation. Thus, d-1a was treated with mCPBA and Tf2NH (1.1 equiv each) in the presence of PhI (20 mol %) at rt for 24 h not to give undeuterated 2a, which would be expected to be derived from intermediate H, but rather to give deuterated d-2a (>96% D). In summary, we have developed the metal-free and regioselective [2 + 2 + 1] cycloaddition-type reactions of alkynes, nitriles, and oxygen atoms catalyzed by iodine(III) species, which is in situ generated from iodoarene precatalyst with mCPBA and Tf2NH. These catalytic systems could be applied to both terminal and internal alkynes with various nitriles, thereby leading to 2,4-disubstituted and 2,4,5trisubstituted oxazoles. Since iodine catalysis for multicomponent reactions has not been previously achieved, our findings not only provide an attractive procedure for the access to highly substituted oxazoles but also open a new possibility for the use of λ3-iodane catalyst in organic synthesis.
Scheme 4. Proposed Catalytic Cycle
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ASSOCIATED CONTENT
* Supporting Information S
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.7b00742. Experimental procedures, characterization data of new compounds, and NMR spectra (PDF)
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PhI(OH)NTf2, in situ generated from ArI and mCPBA in the presence of Tf2NH, would react with alkyne 1 to form intermediate B through the iodoimidation of 1 followed by the ligand exchange of the OH group in intermediate A. Then, the alkenyl(phenyl)iodonium intermediate B would serve as the highly reactive electrophile14 to undergo the nucleophilic vinylic substitution at the β-position with R3CN. Subsequently, the formed intermediate trans-C may be converted to generate cis-C by repeating the addition and elimination of R3CN and then intermediate cis-D and/or E by the ligand exchange of NTf2 group and/or the addition to nitrenium ion with H2O. Finally, after cyclization of intermediate D and/or E, the reductive elimination from intermediate F would lead to the regeneration of ArI along with target oxazoles 2. As an alternative route from trans-C to oxazoles 2, the nucleophilic vinylic substitution at the α-position of trans-C with H2O and/or the ligand coupling of trans-D giving rise to enol trans-G is possibly involved. After trans-G is isomerized to cis-G via keto−enol tautomerization, the cyclization of cis-G yields 2. On the other hand, although alkynyl(phenyl)iodonium intermediate has been known to be formed from terminal
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Akio Saito: 0000-0002-8291-2059 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This work was partially supported by a JSPS Grants-in-Aid for Scientific Research (C) (Grant No. 15K07852) and by the Asahi Glass Foundation. V.V.Z. is also thankful to the National Science Foundation (CHE-1262479).
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REFERENCES
(1) (a) Müller, T. J. J., Ed. Multicomponent Reactions, Science of Synthesis; Thieme: Stuttgart, 2014; Vols. 1 and 2. (b) Tanaka, K., Ed. Transition-Metal-Mediated Aromatic Ring Construction; Wiley: Hoboken, 2013. (c) Croatt, M. P.; Wender, P. A. Eur. J. Org. Chem. 2010, 2010, 19. 2508
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Organic Letters (2) (a) Gulevich, A. V.; Dudnik, A. S.; Chernyak, N.; Gevorgyan, V. Chem. Rev. 2013, 113, 3084. (b) Tomkinson, N. C. O.; Bresciani, S. Heterocycles 2014, 89, 2479. (c) Ibrar, A.; Khan, I.; Abbas, N.; Farooq, U.; Khan, A. RSC Adv. 2016, 6, 93016. (3) (a) He, W.; Li, C.; Zhang, L. J. Am. Chem. Soc. 2011, 133, 8482. (b) Li, X.; Huang, L.; Chen, H.; Wu, W.; Huang, H.; Jiang, H. Chem. Sci. 2012, 3, 3463. (c) See also: Fukumoto, T.; Aso, Y.; Otsubo, T.; Ogura, F. J. Chem. Soc., Chem. Commun. 1992, 1070. (4) (a) Wipf, P. Chem. Rev. 1995, 95, 2115. (b) Yeh, V. S. C. Tetrahedron 2004, 60, 11995. (c) Jin, Z. Nat. Prod. Rep. 2009, 26, 382. (d) Jin, Z. Nat. Prod. Rep. 2011, 28, 1143. (e) Heng, S.; Gryncel, K. R.; Kantrowitz, E. R. Bioorg. Med. Chem. 2009, 17, 3916. (5) (a) Jiang, H.; Huang, H.; Cao, H.; Qi, C. Org. Lett. 2010, 12, 5561. (b) Xue, W.-J.; Li, Q.; Zhu, Y.-P.; Wang, J.-G.; Wu, A.-X. Chem. Commun. 2012, 48, 3485. (c) Xu, Z.; Zhang, C.; Jiao, N. Angew. Chem., Int. Ed. 2012, 51, 11367. (d) Wachenfeldt, H. v.; Röse, P.; Paulsen, F.; Loganathan, N.; Strand, D. Chem. - Eur. J. 2013, 19, 7982. (e) Meng, H.; Zi, Y.; Xu, X.-P.; Ji, S.-J. Tetrahedron 2015, 71, 3819. (6) Metal-catalyzed bimolecular annulation approaches to 2,4disubstituted oxazoles: (a) Connell, R. D.; Tebbe, M.; Gangloff, A. R.; Helquist, P.; Akermark, B. Tetrahedron 1993, 49, 5445. (b) Lee, J. C.; Song, I.-G. Tetrahedron Lett. 2000, 41, 5891. (c) Ritson, D. J.; Spiteri, C.; Moses, J. E. J. Org. Chem. 2011, 76, 3519. (d) Luo, Y.; Ji, K.; Li, Y.; Zhang, L. J. Am. Chem. Soc. 2012, 134, 17412. Metal-free methods: (e) Clauss, K.-U.; Buck, K.; Abraham, W. Tetrahedron 1995, 51, 7181. (f) Graham, T. H. Org. Lett. 2010, 12, 3614. (7) (a) Saito, A.; Taniguchi, A.; Kambara, Y.; Hanzawa, Y. Org. Lett. 2013, 15, 2672. (b) Saito, A.; Kambara, Y.; Yagyu, T.; Noguchi, K.; Yoshimura, A.; Zhdankin, V. V. Adv. Synth. Catal. 2015, 357, 667. (c) Saito, A.; Hyodo, N.; Hanzawa, Y. Molecules 2012, 17, 11046. (d) Saito, A.; Matsumoto, A.; Hanzawa, Y. Tetrahedron Lett. 2010, 51, 2247. (e) Saito, A.; Anzai, T.; Matsumoto, A.; Hanzawa, Y. Tetrahedron Lett. 2011, 52, 4658. (f) Asari, N.; Takemoto, Y.; Shinomoto, Y.; Yagyu, T.; Yoshimura, A.; Zhdankin, V. V.; Saito, A. Asian J. Org. Chem. 2016, 5, 1314. (8) Recent reviews: (a) Ochiai, M.; Miyamoto, K. Eur. J. Org. Chem. 2008, 2008, 4229. (b) Dohi, T.; Kita, Y. Chem. Commun. 2009, 2073. (c) Singh, F. V.; Wirth, T. Chem. - Asian J. 2014, 9, 950. (d) Uyanik, M.; Ishihara, K. ChemCatChem 2012, 4, 177. (e) Finkbeiner, P.; Nachtsheim, B. J. Synthesis 2013, 45, 979. (f) Liu, D.; Lei, A. Chem. Asian J. 2015, 10, 806. (g) Wu, X.-F.; Gong, J.-L.; Qi, X. Org. Biomol. Chem. 2014, 12, 5807. (h) Zhdankin, V. V. In Hypervalent Iodine Chemistry: Preparation, Structure and Synthetic Application of Polyvalent Iodine Compounds; Wiley: Chichester, 2013. (i) Yoshimura, A.; Zhdankin, V. V. Chem. Rev. 2016, 116, 3328. (9) In the oxidative annulations to form oxazoles, a catalytic amount of I2 or iodide salts with tert-butyl hydroperoxide (TBHP) has been employed. See: (a) Wan, C.; Gao, L.; Wang, Q.; Zhang, J.; Wang, Z. Org. Lett. 2010, 12, 3902. (b) Xie, J.; Jiang, H.; Cheng, Y.; Zhu, C. Chem. Commun. 2012, 48, 979. (c) Li, Y.; Guo, F.; Zha, Z.; Wang, Z. Sustainable Chem. Processes 2013, 1, 8. (10) (a) Manna, S.; Antonchick, A. P. Angew. Chem., Int. Ed. 2014, 53, 7324. (b) Yoshimura, A.; Nguyen, K. C.; Klasen, S. C.; Saito, A.; Nemykin, V. N.; Zhdankin, V. V. Chem. Commun. 2015, 51, 7835. (c) Yoshimura, A.; Nguyen, K. C.; Rohde, G. T.; Saito, A.; Yusubov, M. S.; Zhdankin, V. V. Adv. Synth. Catal. 2016, 358, 2340. (d) Yoshimura, A.; Nguyen, K. C.; Klasen, S. C.; Postnikov, P. S.; Yusubov, M. S.; Saito, A.; Nemykin, V. N.; Zhdankin, V. V. Asian J. Org. Chem. 2016, 5, 1128. (11) (a) Dohi, T.; Maruyama, A.; Takenaga, N.; Senami, K.; Minamitsuji, Y.; Fujioka, H.; Caemmerer, S. B.; Kita, Y. Angew. Chem., Int. Ed. 2008, 47, 3787. (b) Dohi, T.; Takenaga, N.; Fukushima, K.; Uchiyama, T.; Kato, D.; Motoo, S.; Fujioka, H.; Kita, Y. Chem. Commun. 2010, 46, 7697. (c) Samanta, R.; Bauer, J. O.; Strohmann, C.; Antonchick, A. P. Org. Lett. 2012, 14, 5518. (d) Lucchetti, N.; Scalone, M.; Fantasia, S.; Muñiz, K. Adv. Synth. Catal. 2016, 358, 2093. (12) Martinez, A. G.; Herrera, A.; Martinez, R.; Teso, E.; Garcia, A.; Osio, J.; Pargada, L.; Unanue, R.; Subramanian, L. R.; Hanack, M. J. Heterocycl. Chem. 1988, 25, 1237.
(13) Miyamoto, K.; Yokota, Y.; Suefuji, T.; Yamaguchi, K.; Ozawa, T.; Ochiai, M. Chem. - Eur. J. 2014, 20, 5447. (14) Ochiai, M.; Kitagawa, Y.; Toyonari, M.; Uemura, K.; Oshima, K.; Shiro, M. J. Org. Chem. 1997, 62, 8001. (15) Selected examples: (a) Souto, J. A.; Becker, P.; Iglesias, Á .; Muñiz, K. J. Am. Chem. Soc. 2012, 134, 15505. (b) Rebrovic, L.; Koser, G. F. J. Org. Chem. 1984, 49, 4700. (c) Kitamura, T.; Lee, C. H.; Taniguchi, H.; Matsumoto, M.; Sano, Y. J. Org. Chem. 1994, 59, 8053. (d) Merritt, E. A.; Olofsson, B. Eur. J. Org. Chem. 2011, 2011, 3690. (e) Dixon, L. I.; Carroll, M. A.; Gregson, T. J.; Ellames, G. J.; Harrington, R. W.; Clegg, W. Eur. J. Org. Chem. 2013, 2013, 2334. (f) Hamnett, D. J.; Moran, W. J. Org. Biomol. Chem. 2014, 12, 4156.
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