Letter pubs.acs.org/OrgLett
Cp*Co(III)-Catalyzed Annulation of Carboxylic Acids with Alkynes Rajib Mandal and Basker Sundararaju* Fine Chemical Laboratory, Department of Chemistry, Indian Institute of Technology Kanpur 208016, Uttar Pradesh, India S Supporting Information *
ABSTRACT: A new procedure for oxidative coupling of aromatic and acrylic acids with alkynes has been developed using abundant, nontoxic, and air stable Cp*Co(III) catalyst. The coupling involves initial cyclometalation via weak chelation-assisted C−H bond activation followed by alkyne coordination, insertion, and reductive elimination leading to diverse isocoumarins (α-pyranones) in good yields under mild conditions.
D
Scheme 1. Carboxylic Acid-Directed C−H Bond Functionalization
irect functionalization of C−H bonds is one of the elegant ways to access molecules that are not feasible by traditional cross coupling methodologies, which requires prefunctionalization.1,2 However, overcoming the limitation of strongly chelating heteroatoms such as N and S is still a major challenge, especially with first row transition metals.3 Since the pioneering work of Matsunaga and Kanai, the use of high valent Cp*Co(III) for C−H bond functionalization has gained significant attention in the past few years due to its unique reactivity and selectivity.4,5 The limitation, however, is the requirement of a heterocycle such as pyridine and its analogue for cobalt-catalyzed C−H bond activation (Scheme 1a).6 The use of carboxylic acid as a weakly coordinating functional group has not been explored until now with cobalt, although amide and other directing groups have been exploited.7,8 Isocoumarin and pyrones are widely distributed in many natural products, which show high biological activity, especially for antimicrobial,9a,b antifungal,9c anti-inflammatory,9d,e antimalarial,9f and anti-HIV.9g In 2007, Miura reported the first oxidative cyclization of aromatic acids with alkynes for the synthesis of isocoumarins via carboxylate-directed C−H bond functionalization (Scheme 1b).10 Since then several groups have reported the synthesis of isocoumarins using various transition metals such as Rh(III),11 Ir(III),12 Ru(II),13 and Pd(II)14 under oxidative conditions (Scheme 1b). To the best of our knowledge, the use of abundant first row transition metals has not been reported using carboxylic acid as a directing group. Our own interest has been focused on the use of base metals for C−H bond functionalization.15 Herein, we report the first cobalt-catalyzed oxidative coupling of carboxylic acids with alkynes using Cp*Co(III) as a catalyst, Cu(II) as an oxidant, and carboxylic acid as a weakly coordinating group (Scheme 1c), leading to a variety of isocoumarins. To begin with, benzoic acid 1a and diphenylacetylene 2a were employed as the reactants with 10 mol % of Cp*Co(CO)I2 as the catalyst in 2,2,2-trifluoroethanol (TFE) (0.2 M). The reaction was carried out at 100 °C for 24 h under an inert atmosphere. Among the various oxidants that were screened, CuO led to the best results with the isocoumarin 3aa isolated in 58% yield (Table 1, entries 1−6). A respectable improvement was observed in the © 2017 American Chemical Society
yield when molecular sieves were introduced (entry 7). As can be seen from Table 1, ionization of cobalt complex by adding silver salt does not have any effect on the yield of 3aa (entry 8). Although several solvents were screened, none of them was found to give better results than TFE (entry 9).16 Excellent yield of 3aa in 92% was obtained when the amount of oxidant was increased from 1.5 to 2 equiv (entry 10). Reduction in the temperature down to 80 °C did not impact the product formation (entry 11). However, further lowering in the temperature led to a drastic reduction in the isolated yield (entry 13). Subsequently, we further examined the influence of an external carboxylate source such as sodium acetate; it is known in the literature that addition of carboxylates promote the reaction. Introduction of NaOAc in 20 mol % led to near quantitative formation of the product at 80 °C (entry 12). At this stage, varying catalyst loadings and other Co-catalysts were explored. These were, unfortunately, not to much avail (entries 15−17). The Received: March 21, 2017 Published: April 27, 2017 2544
DOI: 10.1021/acs.orglett.7b00801 Org. Lett. 2017, 19, 2544−2547
Letter
Organic Letters Table 1. Results of Optimization of the Reactiona
entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
[Co] (mol %) Cp*Co(CO)I2 (10) Cp*Co(CO)I2 (10) Cp*Co(CO)I2 (10) Cp*Co(CO)I2 (10) Cp*Co(CO)I2 (10) Cp*Co(CO)I2 (10) Cp*Co(CO)I2 (10) Cp*Co(CO)I2 (10) Cp*Co(CO)I2 (10) Cp*Co(CO)I2 (10) Cp*Co(CO)I2 (10) Cp*Co(CO)I2 (10) Cp*Co(CO)I2 (10) Cp*Co(CO)I2 (10) Cp*Co(CO)I2 (5) [Cp*CoI2]2 (5) [Cp*CoCl2]2 (5)
oxidant (equiv)
additive (mg)
Ag2CO3 (1.5) AgOAc (1.5) Ag2O (1.5) Mn(OAc)2 (1.5) Cu(OAc)2 (1.5) CuO (1.5) CuO (1.5) CuO (1.5) CuO (2.0) CuO (2.0) CuO (2.0) CuO (2.0) CuO (2.0) CuO (0.5) CuO (2.0) CuO (2.0) CuO (2.0) CuO (2.0)
MS (80) MS (80) MS (80) MS (80) MS (80) MS (80) MS (80) MS (80) MS (80) MS (80) MS (80) MS (80)
temp (°C) 100 100 100 100 100 100 100 100 100 100 80 80 60 80 80 80 80 80
yieldb (%) 21 20 18 n.d. 7 58 73 70c n.d.d 92 92 96e 45e 15e,f 40 60 55 n.d.
a All reactions were carried out under argon atmosphere, unless otherwise stated, using 1a/2a/[Co]/[oxidant]/4 Å MS in 0.2/0.24/0.02/0.3−0.4 mmol at 100 °C in 2,2,2-trifluoroethanol (1 mL). bIsolated yield. c12 mol % of AgSbF6 was added. dNo reaction was observed with solvents such as DCE, trifluorotoluene, o-xylene, CH3CN, etc. e20 mol % of NaOAc was used. fOxygen atmosphere. MS = molecular sieves; TFE = 2,2,2trifluoroethanol; n.d = not determined.
withdrawing groups such as Br-, F-, and -CF3 at various positions of arene led to the corresponding isocoumarins in moderate-togood yields (3ga−3ja). The scope of the reaction could be further extended to thiophene-2-carboxylic acid and naphthalene-1carboxylic acid, leading to their respective isocoumarins (3ka− 3la) in very good isolated yields. To realize the generality of the reaction, methacrylic acid and acrylic acids were tested under the established reaction conditions. Indeed, the reactions led to the corresponding pyrones in moderate-to-excellent yields (3ma−3na). Replacement of carboxylic acids with stronger acid such as sulfonic or phosphinic acids led to no observable formation of the products under conditions employed for the carboxylic acids. The scope of alkynes was further examined as illustrated in Scheme 3. Symmetrical alkynes such as methyl- and fluorosubstituted diarylacetylenes gave the products (3ab−3ad) in excellent yields. Electron-rich alkyne such as 5-decyne, 4-octyne, and benzyl-protected 1,4-but-2-yn diol provided the corresponding isocoumarins (3ae−3ag) smoothly in excellent yields. We also investigated the regioselectivity with electronically biased unsymmetrical internal alkynes. Due to high polarizability of Co− C bond after cyclometalation, it was anticipated that the unsymmetrical alkyne would undergo selective insertion to yield the isocoumarin regioselectively after reductive elimination. For example, when we employed phenylmethylacetylene 2h with benzoic acid, the corresponding isocoumarins were obtained with a regioselectivity of 3.3:1, where the major isomer constitutes the one in which the phenyl attached the α-carbon to the oxygen (3ah). A marginal improvement in the regioselectivity was observed when 4-bromobenzoic acid was used in place of 1a (3fh). Similar selectivity was observed when the annulation was extended to alkyl-aryl/heteroaryl substituted acetylenes (3fi−
Scheme 2. Scope of Acids
control experiments revealed that the product is not formed in the absence of cobalt catalyst (entry 18). With the best conditions in hand, the scope of carboxylic acids (Scheme 2) was examined. Electron donating groups such as Meand tBu- at different positions in the aromatic ring (o-, m-, and p-) gave rise to the corresponding products (3ba−3ea) in excellent yields. p-Methoxy-substituted benzoic acid yielded 3fa in a very good yield. The benzoic acids substituted with electron2545
DOI: 10.1021/acs.orglett.7b00801 Org. Lett. 2017, 19, 2544−2547
Letter
Organic Letters Scheme 3. Scope of Alkynes
Scheme 5. Control Experiments
Scheme 6. Proposed Mechanism
Scheme 4. Overcoming the Limitation of Strong Chelation
3fk). To expand the scope of the reaction, both symmetrical and unsymmetrical alkynes were tested with methacrylic acid. The reactions occurred smoothly providing diverse substitutedpyrones in excellent isolated yields (3me−3mh). The influence of a competing and strongly coordinating pyridyl group was examined with an azaindolyl-substituted benzoic acid 1q, Scheme 4. The reaction led selectively to the product derived by the oxidative coupling of the acid with the alkyne, attesting to the fact the formation of five-membered metallocyle occurs in preference to the six-membered one. To establish the mechanism, control experiments were performed as shown in Scheme 5. Intermolecular competitive experiments were conducted between electron-rich and poor alkynes with benzoic acid. This reaction furnished 3aa and 3ae in 1:1.2 ratio, as established by 1H NMR analysis, indicating that the insertion is faster with electron-rich alkyne than with electronpoor alkyne. Competitive experiments were also conducted with equimolar benzoic acids 1d and 1i with 2a. These reactions yielded the product derived from the benzoic acid containing electron-withdrawing group preferably in 1.4:1 ratio. Further, H/ D exchange experiments in the presence of alkyne 2a show significant amount of deuterium incorporation, suggesting that cyclometalation is reversible. A proposed mechanism for benzoic acid 1 with internal alkynes 2 is shown in Scheme 6. Initial coordination of benzoic acid 1 with
intermediate A followed by reversible cyclometalation may lead to cobaltacycle C. More polarized carbon−cobalt in intermediate C should favor regioselective insertion of alkyne 2 after initial coordination, leading to seven-membered alkenyl intermediate E. The latter may undergo reductive elimination to provide the isocoumarin 3 and Co(I). Cu(II) may reoxidize Co(I) to Co(III), which is the active species regenerated for next catalytic cycle. In conclusion, we have demonstrated an efficient, waste-free and Co-catalyzed oxidative cyclization of benzoic and acrylic acids with internal alkynes for the synthesis of isocoumarins and pyrones in good-to-excellent isolated yields. Good regioselectivity was obtained when unsymmetrical alkynes were employed. We have demonstrated for the first time the use of carboxylic acid as a weakly chelating functional group for C−H bond functionalization using Cp*Co catalyst. We have further shown that the selective carboxylate-directed annulation proceeds 2546
DOI: 10.1021/acs.orglett.7b00801 Org. Lett. 2017, 19, 2544−2547
Letter
Organic Letters
(7) Selected examples using weakly chelating directing group: (a) Lerchen, A.; Vásquez-Céspedes, S.; Glorius, F. Angew. Chem., Int. Ed. 2016, 55, 3208−3211. (b) Lu, Q.; Vásquez-Céspedes, S.; Gensch, T.; Glorius, F. ACS Catal. 2016, 6, 2352−2356. (c) Park, J.; Chang, S. Angew. Chem., Int. Ed. 2015, 54, 14103−14107. (d) Sun, B.; Yoshino, T.; Kanai, M.; Matsunaga, S. Angew. Chem., Int. Ed. 2015, 54, 12968−12972. (e) Ikemoto, H.; Yoshino, T.; Sakata, K.; Matsunaga, S.; Kanai, M. J. Am. Chem. Soc. 2014, 136, 5424−5431. (f) Wang, H.; Moselage, M.; González, M. J.; Ackermann, L. ACS Catal. 2016, 6, 2705−2709. (g) Kong, L.; Yu, S.; Zhou, X.; Li, X. Org. Lett. 2016, 18, 588−591. (h) Zhang, Z. − Z.; Liu, B.; Xu, J. − W.; Yan, S. − Y.; Shi, B. − F. Org. Lett. 2016, 18, 1776−1779. (i) Yu, W.; Zhang, Y.; Liu, Y.; Zhou, Y.; Liu, Z.; Zhang, Y. RSC Adv. 2016, 6, 24768−24772. (j) Lade, D. M.; Pawar, A. B. Org. Chem. Front. 2016, 3, 836−840. (8) Review on Carboxylate directed C−H bond functionalization; see: Pichette Drapeau, M.; Gooβen, L. Chem. - Eur. J. 2016, 22, 18654− 18677. (b) Shi, G.; Zhang, Y. Adv. Synth. Catal. 2014, 356, 1419−1442. (c) De Sarkar, S. D.; Liu, W.; Kozhushkov, S. I.; Ackermann, L. Adv. Synth. Catal. 2014, 356, 1461−1479. (9) (a) Matsuda, H.; Shimoda, M.; Yoshikawa, M. Bioorg. Med. Chem. 1999, 7, 1445−1450. (b) Yoshikawa, M.; Harada, E.; Naitoh, Y.; Inoue, K.; Matsuda, H.; Shimoda, H.; Yamahara, J.; Murakami, N. Chem. Pharm. Bull. 1994, 42, 2225−2230. (c) Nozawa, K.; Yamada, M.; Tsuda, Y.; Kawai, K.; Nakajima, S. Chem. Pharm. Bull. 1981, 29, 2689−2691. (d) Furuta, T.; Fukuyama, Y.; Asakawa, Y. Phytochemistry 1986, 25, 517− 520. (e) Kontogiorgis, C. A.; Savvoglou, K.; Hadjipavlou-Litina, D. J. J. Enzyme Inhib. Med. Chem. 2006, 21, 21−29. (f) Chinworrungsee, M.; Kittakoop, P.; Isaka, M.; Chanphen, R.; Tanticharoen, M.; Thebtaranonth, Y. J. J. Chem. Soc. Perkin Trans.1 2002, 2473−2476. (g) Yu, D. L.; Suzuki, M.; Xie, L.; Morris-Natschke, S. L.; Lee, K. H. Med. Res. Rev. 2003, 23, 322−345. (10) (a) Ueura, K.; Satoh, T.; Miura, M. Org. Lett. 2007, 9, 1407−1409. (b) Ueura, K.; Satoh, T.; Miura, M. J. Org. Chem. 2007, 72, 5362−5367. Also see: (c) Mochida, S.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2009, 74, 6295−6298. (d) Itoh, M.; Shimizu, M.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2013, 78, 11427−11432. (11) (a) Kudo, E.; Shibata, Y.; Yamazaki, M.; Masutomi, K.; Miyauchi, Y.; Fukui, M.; Sugiyama, H.; Uekusa, H.; Satoh, T.; Miura, M.; Tanaka, K. Chem. - Eur. J. 2016, 22, 14190−14194. (b) Li, Q.; Yan, Y.; Wang, X.; Gong, B.; Tang, X.; Shi, J.; Xu, H. E.; Yi, W. RSC Adv. 2013, 3, 23402− 23408. (c) Unoh, Y.; Hirano, K.; Satoh, T.; Miura, M. Tetrahedron 2013, 69, 4454−4458. (d) Shimizu, M.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2009, 74, 3478−3483. (12) Frasco, D. A.; Lilly, C. P.; Boyle, P. D.; Ison, E. A. ACS Catal. 2013, 3, 2421−2429. (13) (a) Singh, K. S.; Sawant, S. G.; Dixneuf, P. H. ChemCatChem 2016, 8, 1046−1050. (b) Prakash, R.; Shekarrao, K.; Gogoi, S. Org. Lett. 2015, 17, 5264−5267. (c) Warratz, S.; Kornhass, C.; Cajaraville, A.; Niepoetter, B.; Stalke, D.; Ackermann, L. Angew. Chem., Int. Ed. 2015, 54, 5513− 5517. (d) Deponti, M.; Kozhushkov, S. I.; Yufit, D. S.; Ackermann, L. Org. Biomol. Chem. 2013, 11, 142−148. (e) Ackermann, L.; Pospech, J.; Graczyk, K.; Rauch, K. Org. Lett. 2012, 14, 930−933. (f) Chinnagolla, R. K.; Jeganmohan, M. Chem. Commun. 2012, 48, 2030−2032. (14) Yu, Y.; Huang, L.; Wu, W.; Jiang, H. Org. Lett. 2014, 16, 2146− 2149. (15) (a) Barsu, N.; Bolli, S. K.; Sundararaju, B. Chem. Sci. 2017, 8, 2431− 2435. (b) Barsu, N.; Rahman, Md. A.; Sen, M.; Sundararaju, B. Chem. Eur. J. 2016, 22, 9135−9138. (c) Sen, M.; Emayavaramban, B.; Barsu, N.; Premkumar, J. R.; Sundararaju, B. ACS Catal. 2016, 6, 2792−2796. (d) Kalsi, D.; Laskar, R. A.; Barsu, N.; Premkumar, J. R.; Sundararaju, B. Org. Lett. 2016, 18, 4198−4201. (f) Barsu, N.; Sen, M.; Sundararaju, B.; Premkumar, J. R. Chem. Commun. 2016, 52, 1338−1341. (g) Barsu, N.; Kalsi, D.; Sundararaju, B. Chem. - Eur. J. 2015, 21, 9364−9368. (h) Sen, M.; Kalsi, D.; Sundararaju, B. Chem. - Eur. J. 2015, 21, 15529−15533. (i) Kalsi, D.; Sundararaju, B. Org. Lett. 2015, 17, 6118−6121. (16) Use of more acidic fluorinated solvents enhances the reactivity; see: (a) Colletto, C.; Islam, S.; Juliá-Hernández, F.; Larrosa, I. J. Am. Chem. Soc. 2016, 138, 1677−1683. (b) Wencel-Delord, J.; Colobert, F. Org. Chem. Front. 2016, 3, 394−400.
smoothly with limitation by the presence of a strongly coordinating pyridine ring obviated.
■
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.7b00801. Experimental methods, optimization of reaction conditions, and other supplementary data (PDF)
■
AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Basker Sundararaju: 0000-0003-1112-137X Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS Financial support provided by SERB (EMR/2016/000136) to carry out this research is gratefully acknowledged. R.M. is thankful to IITK and CSIR for his fellowship.
■
REFERENCES
(1) Dixneuf, P. H.; Doucet, H. C−H Bond Activation and Catalytic Functionalization I; Springer, 2016; pp 1−76. (2) Selected recent reviews on C−H bond functionalization; see: (a) Chen, Z.; Wang, B.; Zhang, J.; Yu, W.; Liu, Z.; Zhang, Y. Org. Chem. Front. 2015, 2, 1107−1295. (b) Ye, B.; Cramer, N. Acc. Chem. Res. 2015, 48, 1308−1318. (c) Wencel-Delord, J.; Glorius, F. Nat. Chem. 2013, 5, 369−374. (d) Davies, H. M. L.; Du Bois, J.; Yu, J.-Q. Chem. Soc. Rev. 2011, 40, 1855−1856. (e) Satoh, T.; Miura, M. Chem. - Eur. J. 2010, 16, 11212− 11222. (f) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624−655. (3) (a) Engle, K. M.; Mei, T. − S.; Wasa, M.; Yu, J. − Q. Acc. Chem. Res. 2012, 45, 788−802. (b) Malik, H. A.; Taylor, B. L. H.; Kerrigan, J. R.; Grob, J. E.; Houk, K. N.; Du Bois, J.; Hamann, L. G.; Patterson, A. W. Chem. Sci. 2014, 5, 2352−2361. (c) Liu, Y. − J.; Xu, H.; Kong, W. − J.; Shang, M.; Dai, H.-X.; Yu, J. Q. Nature 2014, 515, 389−393. (d) Wang, H.; Lorion, M. M.; Ackermann, L. Angew. Chem., Int. Ed. 2016, 55, 10386−10390. (4) Yoshino, T.; Ikemoto, H.; Matsunaga, S.; Kanai, M. Chem. - Eur. J. 2013, 19, 9142−9146. (5) Reviews on Cp*Co(III) catalyzed C−H bond functionalization see: (a) Yoshino, T.; Matsunaga, S. Adv. Synth. Catal. 2017, 359, 1245. (b) Wang, S.; Chen, S. − Y.; Yu, X. − Q. Chem. Commun. 2017, 53, 3165− 3180. (b1) Usman, M.; Ren, Z. − H.; Wang, Y. − Y.; Guan, Z. − H. Synthesis 2017, 49, 1419. (c) Moselage, M.; Li, J.; Ackermann, L. ACS Catal. 2016, 6, 498−525. (d) Yoshikai, N. ChemCatChem 2015, 7, 732− 734. (e) Wei, D.; Zhu, X.; Niu, J. − L.; Song, M. − P. ChemCatChem 2016, 8, 1242−1263. (f) Hyster, T. Catal. Lett. 2015, 145, 458−467. (6) Selected examples on Cp*Co(III) catalyzed C−H bond functionalization strongly chelating directing group using pyridine or its analogues as directing group; see: (a) Kim, J. H.; Greßies, S.; Glorius, F. Angew. Chem., Int. Ed. 2016, 55, 5577−5581. (b) Sun, B.; Yoshino, T.; Matsunaga, S.; Kanai, M. Chem. Commun. 2015, 51, 4659−4661. (c) Li, J.; Ackermann, L. Angew. Chem., Int. Ed. 2015, 54, 3635−3638. (d) Li, J.; Ackermann, L. Angew. Chem., Int. Ed. 2015, 54, 8551−8554. (e) Sauermann, N.; González, M.; Ackermann, L. Org. Lett. 2015, 17, 5316−5319. (f) Zhao, D.; Kim, J. H.; Stegemann, L.; Strassert, C. A.; Glorius, F. Angew. Chem., Int. Ed. 2015, 54, 4508−4511. (g) Patel, P.; Chang, S. ACS Catal. 2015, 5, 853−858. (h) Pawar, A. B.; Chang, S. Org. Lett. 2015, 17, 660− 663. (i) Hummel, J. R.; Ellman, J. A. J. Am. Chem. Soc. 2015, 137, 490− 498. (j) Hummel, J. R.; Ellman, J. A. Org. Lett. 2015, 17, 2400−2403. 2547
DOI: 10.1021/acs.orglett.7b00801 Org. Lett. 2017, 19, 2544−2547
