Rhodium-Catalyzed Directed C–H Amidation of Imidazoheterocycles

Letter pubs.acs.org/OrgLett

Cite This: Org. Lett. XXXX, XXX, XXX−XXX

Rhodium-Catalyzed Directed C−H Amidation of Imidazoheterocycles with Dioxazolones Sadhanendu Samanta, Susmita Mondal, Debashis Ghosh, and Alakananda Hajra* Department of Chemistry, Visva-Bharati (A Central University), Santiniketan 731235, India

Downloaded by ALBRIGHT COLG at 09:58:15:485 on June 12, 2019 from https://pubs.acs.org/doi/10.1021/acs.orglett.9b01832.

S Supporting Information *

ABSTRACT: A Rh(III)-catalyzed directed ortho-amidation of 2-arylimidazoheterocycles using dioxazolone as an amidating reagent has been developed. This protocol is a simple, straightforward, and economic was to afford a variety of N-(2(imidazo[1,2-a]pyridin-2-yl)phenyl)acetamide derivatives with excellent yields. A mechanistic study reveals that a reversible cleavage of C−H bond might be involved in the reaction.

T

Scheme 1. C−H Amidation Reactions of Imidazoheterocycles

he development of efficient methodologies for the construction of C−N bonds has great importance in modern synthetic chemistry owing to the wide occurrence of nitrogen-containing molecules in natural products, pharmaceuticals, agrochemicals, and polymers.1 Traditional methods to construct C(sp2)−N bond include Ullmann−Goldberg reaction, Chan−Lam coupling, and Buchwald−Hartwig amination/amidation reaction.2 Presently, transition-metalcatalyzed C−N bond formation reaction by C−H bond activation provides a highly atom-economical and efficient route in organic synthesis.3 In the reported methods, various coupling partners such as N-fluorobenzenesulfonimide, Ncarboxylate, N-tosylates, and azides have been used in C−H amidation reactions.4 In recent times, dioxazolone has been explored as amidating reagent as it is safe and shows higher coordination affinity with the metal center of metallacyclic intermidates.5 Pioneering efforts have been made by Chang, Ackermann, Ellman, Li, and others for the directing group mediated C−H amidation reactions using Ir(III), Rh(III), and Co(III) catalysts.6,7 Moreover, Bolm reintroduced dioxazolones for N-acylnitrene transfer to sulfides and sulfoxides.6c As an important N-heterocycle, imidazo[1,2-a]pyridine is recognized as a privileged heterocyclic scaffold and widely found in many natural products and pharmaceuticals.8a These derivatives exhibit a wide range of biological activities such as antiulcer, antiviral, antibacterial, antifungal, antiprotozoal, etc.8b In particular, amido-substituted imidazo[1,2-a]pyridine is the core structure of several marketed drugs such as alpidem, zolpidem, saripidem, etc.9 Therefore, practical methodologies for the synthesis of amido-substituted imidazoheterocycles are highly desirable and will be of great interest to synthetic chemists (Scheme 1a,b).10 Pleasingly, most of these reported methods provide functionalization at the C-3 position of © XXXX American Chemical Society

imidazoheterocycles.11 However, to the best of our knowledge, there is no method for the direct chelation-assisted orthoC(Sp2)−H amidation reaction with 2-arylimidazopyridine through C−H activation.12 In our continuing efforts on the synthesis and functionalization of imidazopyridine,13 herein we report a rhodium-catalyzed ortho-selective C−H amidation reaction of 2-arylimidazoheterocycles with dioxazolones to afford N-(2-(imidazo[1,2-a]pyridin-2-yl)phenyl)acetamide derivatives through C−H activation (Scheme 1c). Initially, we started our work using 2-phenylimidazo[1,2a]pyridine (1a) and 3-methyl-1,4,2-dioxazol-5-one (2a) as Received: May 27, 2019

A

DOI: 10.1021/acs.orglett.9b01832 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters Scheme 2. Scope of Imidazoheterocyclesa,b

model substrates in the presence of [Cp*RhCl2]2 (Cp* = pentamethylcyclopentadien) and AgSbF6 in toluene at 110 °C. The results are summarized in Table 1. Gratifyingly, the Table 1. Optimization of the Reaction Conditionsa

entry

catalyst

additives

solvent

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

[Cp*RhCl2]2 [Cp*RhCl2]2 [Cp*RhCl2]2 [Cp*RhCl2]2 [Cp*RhCl2]2 [Cp*RhCl2]2 [Cp*RhCl2]2 [Cp*RhCl2]2 [Cp*RhCl2]2 [Cp*RhCl2]2 Rh(PPh3)3Cl RhCl3 [Ru(p-cy)Cl2]2 [Cp*RhCl2]2 [Cp*RhCl2]2 [Cp*RhCl2]2

AgSbF6 AgSbF6 AgSbF6 AgSbF6 AgSbF6 AgSbF6 AgSbF6 AgOAc Ag2CO3 AgOTf AgSbF6 AgSbF6 AgSbF6 AgSbF6 AgSbF6 AgSbF6

toluene CH3CN 1,2-DCB 1,4-dioxane 1,2-DCE DMF THF 1,2-DCE 1,2-DCE 1,2-DCE 1,2-DCE 1,2-DCE 1,2-DCE 1,2-DCE 1,2-DCE 1,2-DCE

yield (%) 54 11 89

15 17 12

a

Reaction conditions: 0.2 mmol of 1, 0.22 mmol of 2a in the presence of 2 mol % of [Cp*RhCl2]2 and 20 mol % of AgSbF6 in 2 mL of 1,2DCE at 110 °C for 5 h. bIsolated yields.

compounds like −OMe-substituted derivative (1d) afforded the selective amidated products in excellent yields (3ba−3da). Halogen (F, Cl, and I) containing substrates successfully gave the desired products without any difficulties (3ea−3ga). Other heterocyclic compounds like benzo[d]imidazo[2,1-b]thiazole and imidazo[2,1-b]thiazole were also well tolerable under the optimized reaction conditions (3ia−3ka). Next, imidazopyridine derivatives with a wide range of substituents on the phenyl ring were examined (Scheme 3).

21 51b, 87c 86d 90e

a

Reaction conditions: All reactions were carried out with 0.2 mmol of 1a, 0.22 mmol of 2a, 2 mol % catalyst, and 20 mol % of additives in 2 mL of solvent for 5 h at 110 °C. bStirred at 90 °C. cStirred at 130 °C. d Under Ar. e2.4 equiv of 2a was used.

desired amidated product, N-(2-(imidazo[1,2-a]pyridin-2-yl)phenyl)acetamide (3aa), was obtained in 54% yield after 5 h (Table 1, entry 1). Inspired by this initial result, we checked the effect of various common solvents like CH3CN, 1,2-DCB, 1,4-dioxane, 1,2-DCE, DMF, and THF (Table 1, entries 2−7). The results showed that 1,2-DCE was the most effective solvent in providing the desired product in 89% yield (Table 1, entry 5). The reaction did not proceed at all in CH3CN, 1,4dioxane, DMF, and THF. Further optimization was performed using different silver salts such as AgOAc, Ag2CO3, and AgOTf (Table 1, entries 8−10). But in all these cases, only a trace amount of amidated product was obtained. No product was formed in the presence of other rhodium catalysts such as Rh(PPh3)3Cl and RhCl3 (Table 1, entries 11 and 12). A lower yield of the product was obtained in the presence of 2 mol % of [Ru(p-cy)Cl2]2 (Table 1, entry 13). No significant improvement of the yield was observed on decreasing as well as increasing the temperature (Table 1, entry 14). The reaction worked well under argon atmosphere (Table 1, entry 15). Furthermore, bis-amidated product was not obtained in the presence of 2.4 equiv of 2a (Table 1, entry 16). Finally, the optimal reaction conditions was achieved using 2 mol % of [Cp*RhCl2]2 and 20 mol % of AgSbF6 in 1,2-DCE at 110 °C for 5 h under ambient air (Table 1, entry 5). With the optimized reaction conditions in hand, we next examined the scope of this methodology, and the results are summarized in the Scheme 2. At first, we checked the effect of substituents on the pyridine ring of imidazo[1,2-a]pyridine derivatives. Imidazopyridines containing −CH3 substituent at different positions of the pyridine ring and electron-donating

Scheme 3. Substrate Scope of the Present Methoda,b

a

Reaction conditions: 0.2 mmol of 1, 0.22 mmol of 2a in the presence of 2 mol % of [Cp*RhCl2]2 and 20 mol % of AgSbF6 in 2 mL of 1,2DCE at 110 °C for 5 h. bIsolated yields.

Imidazo[1,2-a]pyridine with electron-donating substituents like −Me and −OMe provided the corresponding products 3la and 3ma in 88% and 82% yields, respectively. The singlecrystal X-ray analysis of 3ma was performed to confirm the structure of the N-(2-(imidazo[1,2-a]pyridin-2-yl)-5methoxyphenyl)acetamide.14 B

DOI: 10.1021/acs.orglett.9b01832 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters Imidazopyridine containing both a halogen like −F, −Cl, or −Br and a strong electron-withdrawing group, such as −CN, −CF3, and −NO2, on the phenyl ring of imidazo[1,2a]pyridine reacted well with 3-methyl-1,4,2-dioxazol-5-one to afford the ortho-amidated product in excellent yields (3na− 3sa). It is notable that the marketed drug zolimidine was also amidated under the present reaction conditions with 89% yield (3ta). To our delight, the naphthyl- and thiophene-substituted imidazopyridines afforded the desired amidated products with moderate to good yields (3ua and 3va). To access the general applicability of the protocol, a variety of substituted dioxazolone were examined, as shown in Scheme 4. Dioxazolones bearing both electron-donating as well as

In order to investigate the mechanism of this reaction, isotope-labeling experiments were initially carried out by using 1a with D2O under our standard conditions for 5 h (Scheme 6).12e The 1H NMR analysis showed that 95% deuterium was Scheme 6. Control Experiments

Scheme 4. Substrate Scope of Dioxazolonesa,b

incorporated at the ortho-position of the phenyl ring, which suggests that a reversible cleavage of C−H bond might be involved in the reaction. Additionally, a kinetic isotope experiment15 involving 1a and 1a-d3 with 2a as the representative reactants resulted KH/KD = 1.23. Moreover, the parallel reactions of 1a and 1a-d3 with 2a exhibited KH/KD = 1.38 after 2 h, which indicates that Rh-catalyzed C−H bond cleavage may not be involved in the rate-determining step. However, acetamide (5) and benzamide (6) did not respond to this reaction. Based on the experimental results and previous literature reports,6,7,16 we have proposed a plausible mechanism of this reaction as depicted in Scheme 7. First, the exposure of

a

Reaction conditions: 0.2 mmol of 1, 0.22 mmol of 2 in the presence of 2 mol % of [Cp*RhCl2]2 and 20 mol % of AgSbF6 in 2 mL of 1,2DCE at 110 °C for 14 h. bIsolated yields.

electron-withdrawing aryl substituents were reacted well with 1a to give the desired amidated products (3ac−3ag) in good to excellent yields. Gratifyingly, furyl and cyclohexyl functional group substituted dioxazolones 2h and 2i could be successfully converted to the corresponding products 3ah and 3ai in 69% and 94% yields, respectively. The gram-scale reaction was performed between 1a and 2a in the usual laboratory setup (Scheme 5). The amidated product (3aa) was obtained in 83% yield, which suggests the practical applicability of the present methodology. The synthetic utility of the protocol was studied using 3aa as a starting material. Upon reflux in aq KOH/MeOH for 24 h, the acyl group was deprotected to produce 4aa in 89% yield.6b

Scheme 7. Plausible Mechanistic Pathway

Scheme 5. Scale-up Synthesis of 3aa and Deprotection

C

DOI: 10.1021/acs.orglett.9b01832 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters

(3) (a) Cho, S. H.; Kim, J. Y.; Kwak, J.; Chang, S. Chem. Soc. Rev. 2011, 40, 5068−5083. (b) Collet, F.; Lescot, C.; Dauban, P. Chem. Soc. Rev. 2011, 40, 1926−1936. (c) Louillat, M.-L.; Patureau, F. W. Chem. Soc. Rev. 2014, 43, 901−910. (d) Yoo, E. J.; Ma, S.; Mei, T.-S.; Chan, K. S. L.; Yu, J.-Q. J. Am. Chem. Soc. 2011, 133, 7652−7655. (e) Matsubara, T.; Asako, S.; Ilies, L.; Nakamura, E. J. Am. Chem. Soc. 2014, 136, 646−649. (f) Rit, R. K.; Shankar, M.; Sahoo, A. K. Org. Biomol. Chem. 2017, 15, 1282−1293. (4) (a) Sun, K.; Li, Y.; Xiong, T.; Zhang, J.; Zhang, Q. J. Am. Chem. Soc. 2011, 133, 1694−1697. (b) Takamatsu, K.; Hayashi, Y.; Kawauchi, S.; Hirano, K.; Miura, M. ACS Catal. 2019, 9, 5336− 5344. (c) Ng, K.-H.; Chan, A. S. C.; Yu, W.-Y. J. Am. Chem. Soc. 2010, 132, 12862−12864. (d) Hu, X.-H.; Yang, X.-F.; Loh, T.-P. ACS Catal. 2016, 6, 5930−5934. (e) Ghosh, T.; Maity, P.; Ranu, B. C. J. Org. Chem. 2018, 83, 11758−11767. (5) (a) Lei, H.; Rovis, T. J. Am. Chem. Soc. 2019, 141, 2268−2273. (b) Knecht, T.; Mondal, S.; Ye, J.-H.; Das, M.; Glorius, F. Angew. Chem., Int. Ed. 2019, 58, 7117−7121. (c) Liang, Y.; Liang, Y.-F.; Tang, C.; Yuan, Y.; Jiao, N. Chem. - Eur. J. 2015, 21, 16395−16399. (6) (a) Park, Y.; Park, K. T.; Kim, J. G.; Chang, S. J. Am. Chem. Soc. 2015, 137, 4534−4542. (b) Mei, R.; Loup, J.; Ackermann, L. ACS Catal. 2016, 6, 793−797. (c) Bizet, V.; Buglioni, L.; Bolm, C. Angew. Chem., Int. Ed. 2014, 53, 5639−5642. (d) Hoang, G. L.; Halskov, K. S.; Ellman, J. A. J. Org. Chem. 2018, 83, 9522−9529. (e) Xia, J.; Yang, X.; Li, Y.; Li, X. Org. Lett. 2017, 19, 3243−3246. (7) (a) Bera, S. S.; Sk, M. R.; Maji, M. S. Chem. - Eur. J. 2019, 25, 1806−1811. (b) Wang, S.-B.; Gu, Q.; You, S.-L. Organometallics 2017, 36, 4359−4362. (c) Liu, Y.-H.; Li, P.-X.; Yao, Q.-J.; Zhang, Z.Z.; Huang, D.-Y.; Le, M. D.; Song, H.; Liu, L.; Shi, B.-F. Org. Lett. 2019, 21, 1895−1899. (d) Jeon, B.; Yeon, U.; Son, J.-Y.; Lee, P. H. Org. Lett. 2016, 18, 4610−4613. (8) (a) Enguehard-Gueiffier, C.; Gueiffier, A. Mini-Rev. Med. Chem. 2007, 7, 888−899. (b) Baviskar, A. T.; Amrutkar, S. M.; Trivedi, N.; Chaudhary, V.; Nayak, A.; Guchhait, S. K.; Banerjee, U. C.; Bharatam, P. V.; Kundu, C. N. ACS Med. Chem. Lett. 2015, 6, 481−485. (9) (a) Shakoor, S. M. A.; Kumari, S.; Khullar, S.; Mandal, S. K.; Kumar, A.; Sakhuja, R. J. Org. Chem. 2016, 81, 12340−12349. (b) Bagdi, A. K.; Santra, S.; Monir, K.; Hajra, A. Chem. Commun. 2015, 51, 1555−1575. (10) (a) Mondal, S.; Samanta, S.; Jana, S.; Hajra, A. J. Org. Chem. 2017, 82, 4504−4510. (b) Lu, S.; Tian, L.-L.; Cui, T.-W.; Zhu, Y.-S.; Zhu, X.; Hao, X.-Q.; Song, M.-P. J. Org. Chem. 2018, 83, 13991− 14000. (c) Sun, K.; Mu, S.; Liu, Z.; Feng, R.; Li, Y.; Pang, K.; Zhang, B. Org. Biomol. Chem. 2018, 16, 6655−6658. (d) Kielesiński, Ł.; Tasior, M.; Gryko, D. T. Org. Chem. Front. 2015, 2, 21−28. (e) Gao, Y.; Chen, S.; Lu, W.; Gu, W.; Liu, P.; Sun, P. Org. Biomol. Chem. 2017, 15, 8102−8109. (11) (a) Cao, H.; Lei, S.; Li, N.; Chen, L.; Liu, J.; Cai, H.; Qiu, S.; Tan, J. Chem. Commun. 2015, 51, 1823−1825. (b) Yan, K.; Yang, D.; Wei, W.; Lu, S.; Li, G.; Zhao, C.; Zhang, Q.; Wang, H. Org. Chem. Front. 2016, 3, 66−70. (c) Nitha, P. R.; Joseph, M. M.; Gopalan, G.; Maiti, K. K.; Radhakrishnan, K. V.; Das, P. Org. Biomol. Chem. 2018, 16, 6430−6437. (d) Sun, P.; Jiang, M.; Wei, W.; Min, Y.; Zhang, W.; Li, W.; Yang, D.; Wang, H. J. Org. Chem. 2017, 82, 2906−2913. (12) (a) Bagdi, A. K.; Hajra, A. Chem. Rec. 2016, 16, 1868−1885. (b) Pericherla, K.; Kaswan, P.; Pandey, K.; Kumar, A. Synthesis 2015, 47, 887−912. (c) Ravi, C.; Adimurthy, S. Chem. Rec. 2017, 17, 1019− 1038. (d) Yu, Y.; Su, Z.; Cao, H. Chem. Rec. 2018, DOI: 10.1002/ tcr.201800168. (e) Zhu, X.; Shen, X.-J.; Tian, Z.-Y.; Lu, S.; Tian, L.L.; Liu, W.-B.; Song, B.; Hao, X.-Q. J. Org. Chem. 2017, 82, 6022− 6031. (f) Li, Y.; Wang, F.; Yu, S.; Li, X. Adv. Synth. Catal. 2016, 358, 880−886. (13) (a) Samanta, S.; Mondal, S.; Santra, S.; Kibriya, G.; Hajra, A. J. Org. Chem. 2016, 81, 10088−10093. (b) Samanta, S.; Hajra, A. J. Org. Chem. 2019, 84, 4363−4371. (c) Samanta, S.; Hajra, A. Chem. Commun. 2018, 54, 3379−3382. (14) Further information can be found in the CIF file. These crystal data were deposited in the Cambridge Crystallographic Data Centre and assigned as CCDC 1918579.

[Cp*RhCl2]2 to AgSbF6 provides the active cationic Rh(III) species,16 which then forms a chelate ring with N1-atom of imidazo[1,2-a]pyridines (1a) to afford five-membered rodacycle A via a reversible C−H rodation of 1a. Next, coordination of A with dioxazolones (2a) generates an intermediate B.6a After that, a six-membered Rh(III) species C is formed by the migratory insertion of 2a and the release of CO2. Finally, proto-derhodation of C furnishes the desired product 3aa along with the regeneration of the active Rh(III) catalyst.7,16 In summary, we have developed a rhodium-catalyzed orthoselective C−H amidation of 2-arylimidazoheterocycles with dioxazolones through C−H activation. This reaction provides a step- and atom-economical protocol for C−N bond formation, releasing carbon dioxide as a single byproduct. To the best of our knowledge, this is the first report for the synthesis of N-(2(imidazo[1,2-a]pyridin-2-yl)phenyl)acetamide derivatives. We believe that this strategy has potential applications in organic synthesis, medicinal chemistry, as well as material sciences.

■

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.9b01832. Experimental procedures and spectral data (PDF) Accession Codes

CCDC 1918579 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

■

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Sadhanendu Samanta: 0000-0003-2215-9189 Susmita Mondal: 0000-0002-8795-942X Alakananda Hajra: 0000-0001-6141-0343 Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS A.H. acknowledges financial support from SERB-DST (Grant No. EMR/2016/001643). S.S. thanks UGC, S.M. thanks CSIR, and D.G. thanks UGC (DSK) for fellowships.

■

REFERENCES

(1) (a) Amino Group Chemistry, From Synthesis to the Life Sciences; Ricci, A., Ed.; Wiley-VCH: Weinheim, 2007. (b) Hili, R.; Yudin, A. K. Nat. Chem. Biol. 2006, 2, 284−287. (c) Candeias, N. R.; Branco, L. C.; Gois, P. M. P.; Afonso, C. A. M.; Trindade, A. F. Chem. Rev. 2009, 109, 2703−2802. (2) (a) Hartwig, J. F. Acc. Chem. Res. 2008, 41, 1534−1544. (b) Park, Y.; Kim, Y.; Chang, S. Chem. Rev. 2017, 117, 9247−9301. (c) Brasche, G.; Buchwald, S. L. Angew. Chem., Int. Ed. 2008, 47, 1932−1934. (d) Hatakeyama, T.; Yoshimoto, Y.; Ghorai, S. K.; Nakamura, M. Org. Lett. 2010, 12, 1516−1519. D

DOI: 10.1021/acs.orglett.9b01832 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters (15) (a) Modi, A.; Sau, P.; Chakraborty, N.; Patel, B. K. Adv. Synth. Catal. 2019, 361, 1368−1375. (b) Maji, A.; Guin, S.; Feng, S.; Dahiya, A.; Singh, V. K.; Liu, P.; Maiti, D. Angew. Chem., Int. Ed. 2017, 56, 14903−14907. (16) (a) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624−655. (b) Rej, S.; Chatani, N. Angew. Chem., Int. Ed. 2019, 58, 8304−8329. (c) Song, G.; Li, X. Acc. Chem. Res. 2015, 48, 1007−1020. (d) Karthikeyan, J.; Yoshikai, N. Org. Lett. 2014, 16, 4224−4227. (e) Sueki, S.; Kuninobu, Y. Chem. Commun. 2015, 51, 7685−7688. (f) Takada, Y.; Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima, K. Org. Lett. 2006, 8, 2515−2517. (g) Dutta, C.; Sainaba, A. B.; Choudhury, J. Chem. Commun. 2019, 55, 854−857.

E

DOI: 10.1021/acs.orglett.9b01832 Org. Lett. XXXX, XXX, XXX−XXX