Direct Alkenylation of Allylbenzenes via Chelation-Assisted C–C Bond

Communication Cite This: J. Am. Chem. Soc. 2018, 140, 9788−9792

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Direct Alkenylation of Allylbenzenes via Chelation-Assisted C−C Bond Cleavage Shunsuke Onodera, Soya Ishikawa, Takuya Kochi, and Fumitoshi Kakiuchi* Department of Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan

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S Supporting Information *

Scheme 1. Metal-Catalyzed Cleavage of Unstrained C−C Bonds

ABSTRACT: A novel method for direct transformation of allyl groups in allylbenzene derivatives to alkenyl groups via rhodium-catalyzed C−C bond cleavage is reported. The alkenylation with styrenes of allylbenzenes containing pyridyl and pyrazolyl groups as a directing group proceeded efficiently to give alkenylation products. We also developed a new protocol for transformation of an ortho-prenylated phenol to an aniline derivative.

C

atalytic bond formation via cleavage of unreactive bonds has attracted considerable attention and has provided unconventional, efficient routes to synthesize complex organic molecules. Particularly, metal-catalyzed conversion of inert, unstrained C−C bonds to new C−C bonds has been recognized as one of the most challenging transformations in this field, because of the limited availability of effective methods to cleave such thermodynamically stable bonds.1 Formation of a stable chelate has been frequently used as a driving force for catalytic cleavage of the unstrained C−C bonds, including pioneering works of Suggs,2 Jun,3 and Murai4 as well as recent works of Douglas,5 Shi,6 Wang,7 Dong,8 Morandi,9 Johnson,10 Xu and Wei,11 but the cleavable bonds have been limited to those right next to a heteroatom such as ketones, imines, and alcohols (Scheme 1). Here we report a chelation-assisted catalytic alkenylation of allylbenzene derivatives via C−C bond cleavage. A simple Cp*Rh catalyst/alcohol system was found to be effective for the conversion of allylbenzenes possessing a directing group to stilbene derivatives. Many reactions involving cleavage of allylic C−C bonds have been reported but mostly proceed via either formation of ketones from homoallyl alcohols12 or generation of stabilized carbanions.13 This deallylative alkenylation reported here is the first catalytic C−C bond formation involving chelation-assisted regioselective cleavage of bonds between an aromatic ring and an allyl group.14 When a reaction of a prenylbenzene derivative bearing a pyridyl directing group (1a) with styrene (2a) was performed in the presence of 4 mol % of [Cp*Rh(CH3CN)3][SbF6]2 (3) under EtOH refluxing conditions for 24 h, substitution of the prenyl group with a β-styryl group proceeded to give alkenylation product 4aa in 84% NMR yield (Table 1, entry 1). Several rhodium catalysts were then examined for this alkenylation. While the reaction using a combination of [Cp*RhCl2]2 and AgSbF6 provided 4aa in a lower yield (entry 2), only a trace amount of 4aa was obtained in the © 2018 American Chemical Society

absence of AgSbF6 (entry 3). The use of other rhodium catalysts such as Cp*Rh(OAc)2·H2O, RhH(CO)(PPh3)3, and RhH(PPh3)4 resulted in the formation of less than a trace amount of 4aa (entries 4−6). Finally, extension of the reaction time to 48 h was found to improve the NMR yield to 91%, and product 4aa was isolated in 87% yield (entry 7). The substrate scope was then examined for the pyridyldirected deallylative alkenylation (Table 2). First, the reactions of 1a with styrenes having various substituents were investigated. High yields (86−92%) of the alkenylation products were obtained in the reactions with styrenes having a variety of para substituents including electron-donating (Me, t Bu) and -withdrawing (CF3) groups and halogeno groups (F, Cl, Br). The reaction with 2-methylstyrene also proceeded to give the corresponding alkenylation product 4ah in 78% yield. In the case of 2-vinylnaphthalene, alkenylation product 4ai was obtained in 70% yield by increasing the catalyst loading to 8 mol %. Next, the deallylative alkenylation was examined for arylpyridine substrates possessing various substituents. While the reaction of a substrate bearing a methoxy group at the position ortho to the pyridyl group afforded a 92% yield of product 4ba, installation of an electron-withdrawing trifluorReceived: April 6, 2018 Published: May 22, 2018 9788

DOI: 10.1021/jacs.8b03718 J. Am. Chem. Soc. 2018, 140, 9788−9792

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Journal of the American Chemical Society Table 1. Deallylative Alkenylation of 1a with Styrene (2a)a

entry

catalyst

yieldb

1 2c 3d 4 5 6 7f

[Cp*Rh(CH3CN)3][SbF6]2 (3) [Cp*RhCl2]2/AgSbF6 [Cp*RhCl2]2 Cp*Rh(OAc)2·H2O RhH(CO)(PPh3)3 RhH(PPh3)4 3

84% 72% trace trace nde nde 91% (87%)g

yield, and no byproduct formation by cleaving off the meta prenyl group was observed. The reaction of a 2-(3methylpyridyl)benzene derivative also gave the corresponding alkenylation product 4ia in 72% yield. In the reactions of substrates possessing two ortho prenyl groups, both prenyl groups can be converted to alkenyl groups (Scheme 2). While the reaction of a substrate having a methoxy Scheme 2. Deallylative Alkenylation of Arylpyridines Possessing Two Ortho Prenyl Groups

a

Reaction conditions: 1a (0.3 mmol), 2a (0.9 mmol), catalyst (0.012 mmol), EtOH (0.6 mL), reflux. bYields were determined by 1H NMR using allylbenzene as an internal standard. cPerformed with 0.006 mmol (2 mol %) of [Cp*RhCl2]2 and 0.024 mmol (8 mol %) of AgSbF6. dPerformed with 0.006 mmol (2 mol %) of [Cp*RhCl2]2. e Not detected. fPerformed for 48 h. gThe isolated yield is shown in parentheses.

Table 2. Deallylative Alkenylation of Arylpyridines 1 with Styrene Derivatives 2a

group at the meta position (1j) provided mono- and dialkenylation products, 4ja and 5ja, in 10 and 66% yields, respectively, installation of a triisopropylsiloxy group at the meta position (1k) seemed to suppress the alkenylation at the more hindered site to provide monoalkenylation product 4ka as a major product. The deallylative alkenylation was also examined with substrates having an allyl group other than a prenyl group (eq 1). The alkenylation of an arylpyridine possessing a

a

Reaction conditions: 1 (0.3 mmol), 2 (0.9 mmol), 3 (0.012 mmol), EtOH (0.6 mL), reflux (90 °C), 48 h. Isolated yields are shown. b Performed with 8 mol % (0.024 mmol) of 3 in 3.0 mL of EtOH.

methallyl group (1l) gave the corresponding product 4aa in 76% yield. The reaction of a substrate with a simple allyl group (1m) also proceeded, but the product yield was decreased to 57%, because the C−C bond formation with the double bond in another molecule of 1m competed with the reaction with 2a. The pyrazolyl group was also found to function as an effective directing group16 for this deallylative alkenylation (Table 3). When arylpyrazole 6a was reacted with 3 equiv of styrene 2a in 2.4 mL of EtOH solvent, alkenylation product 7aa was obtained in 80% isolated yield. The electronic nature of styrenes did not seem to have significant influence on the

omethyl group instead of the methoxy group reduced the product yield to 35%. The alkenylation of substrates having meta-substituents such as NMe2, Me, Ph, and CF3 proceeded efficiently to give the corresponding alkenylation products 4da−ga in 75−97% yields.15 The reaction of a 2-(2pyridyl)benezene derivative possessing prenyl groups at both 2- and 5-positions (ortho and meta positions) only convert the ortho prenyl group into an alkenyl group to provide 4ha in 68% 9789

DOI: 10.1021/jacs.8b03718 J. Am. Chem. Soc. 2018, 140, 9788−9792

Communication

Journal of the American Chemical Society

In order to investigate the fate of the cleaved allyl group in the alkenylation reaction, the reaction of allylbenzene derivative 1n with 2a was performed (Scheme 3). Although 47% of

Table 3. Pyrazolyl-Directed Deallylative Alkenylation of Allylbenzene Derivatives 6 with Styrene Derivatives 2a

Scheme 3. Detection of the Cleaved Allyl Group

substrate 1n still remains unreacted after 12 h, the reaction gave a 43% NMR yield of the corresponding alkenylation product 4ea along with 3-(4-bromophenyl)-1-propene in 43% NMR yield. No formation of 1-(4-bromophenyl)-1-propene was observed by GC-MS measurement. The result of this experiment supports the proposed catalytic cycle shown in Figure 1, in which the C−C bond was cleaved via hydrometalation/β-carbon elimination rather than direct oxidative addition to give an allylrhodium intermediate. ortho-Prenylated phenols are a class of easily accessible compounds and can be found in many molecules of biological interest.21 Therefore, application of the deallylative alkenylation to transformation of an ortho-prenylated phenol was examined (Figure 2). First, ortho-prenylated phenol 8 was converted to an

a

Reaction conditions: 6 (0.3 mmol), 2 (0.9 mmol), 3 (0.012 mmol), EtOH (2.4 mL), reflux (90 °C), 48 h.

reaction efficiency, and styrenes having a variety of substituents can be applied for this reaction to form the corresponding alkenylation products 7aa−7ah in 64−86% yields. Substrates possessing a substituent other than a methyl group such as isopropyl and methoxy groups can also be converted to alkenylation products 7ba and 7ca in high yields. A possible catalytic cycle of the deallylative alkenylation is shown in Figure 1. Coordination of substrate 1 or 6 to

Figure 2. Transformation of an ortho-prenylated phenol to an aniline derivative.

aryl triflate, and palladium-catalyzed coupling with a pyrazole derivative,22 followed by deprotection, gave arylpyrazole 6d. The deallylative alkenylation of 6d with styrene (2a) provided the corresponding stilbene derivative 7da. Finally, the reaction of 7da with TMSCl in the presence of TMPMgCl·LiCl,23 followed by treatment with HCl in MeOH, provided orthoalkenylated aniline 9. In conclusion, a novel method for direct conversion of allyl groups in allylbenzene derivatives to alkenyl groups via C−C bond cleavage is described. The reaction proceeded without additives only in the presence of a rhodium catalyst in EtOH solvent. We also developed a new protocol for transformation of an ortho-prenylated phenol to an ortho-alkenylated aniline derivative. We believe the catalytic cycle involving the chelation-assisted C−C bond cleavage via a hydrometalation/

Figure 1. Proposed mechanism of the deallylative alkenylation.

rhodium-hydride species A, generated in situ from the Cp*Rh complex and EtOH,17,18 gives complex B, and subsequent hydrometalation provides alkyl rhodium complex C. β-Carbon elimination then proceeds to give D with the assistance of stable five-membered chelate formation.6c−f,9 Alkene exchange with 2 occurs to form rhodacycle E, and carbometalation, followed by β-hydride elimination and alkene dissociation, provides the alkenylation product 4 or 7 with the regenerated complex A. Many examples of catalytic reactions via C−C bond cleavage by β-carbon elimination has been reported,19 but the β-carbon elimination mostly occurs from an alkoxide complex to generate carbonyl compounds.20 9790

DOI: 10.1021/jacs.8b03718 J. Am. Chem. Soc. 2018, 140, 9788−9792

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Journal of the American Chemical Society β-carbon elimination pathway can be applicable to other reactions, and development of new reactions based on this strategy is currently in progress.

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(7) Wang, J.; Chen, W.; Zuo, S.; Liu, L.; Zhang, X.; Wang, J. Angew. Chem., Int. Ed. 2012, 51, 12334−12338. (8) (a) Zeng, R.; Dong, G. J. Am. Chem. Soc. 2015, 137, 1408−1411. (b) Xia, Y.; Lu, G.; Liu, P.; Dong, G. Nature 2016, 539, 546−550. (c) Zeng, R.; Chen, P.-h.; Dong, G. ACS Catal. 2016, 6, 969−973. (d) Xia, Y.; Wang, J.; Dong, G. Angew. Chem., Int. Ed. 2017, 56, 2376− 2380. (e) Rong, Z.-Q.; Lim, H. N.; Dong, G. Angew. Chem., Int. Ed. 2018, 57, 475−479. (9) Ozkal, E.; Cacherat, B.; Morandi, B. ACS Catal. 2015, 5, 6458− 6462. (10) Dennis, J. M.; Compagner, C. T.; Dorn, S. K.; Johnson, J. B. Org. Lett. 2016, 18, 3334−3337. (11) Zhao, T.-T.; Xu, W.-H.; Zheng, Z.-J.; Xu, P.-F.; Wei, H. J. Am. Chem. Soc. 2018, 140, 586−589. (12) For an overview: (a) Yorimitsu, H.; Oshima, K. Bull. Chem. Soc. Jpn. 2009, 82, 778−792. For selected examples: (b) Kondo, T.; Kodoi, K.; Nishinaga, E.; Okada, T.; Morisaki, Y.; Watanabe, Y.; Mitsudo, T. J. Am. Chem. Soc. 1998, 120, 5587−5588. (c) Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima, K. J. Am. Chem. Soc. 2006, 128, 2210−2211. (d) Iwasaki, M.; Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima, K. J. Am. Chem. Soc. 2007, 129, 4463−4469. (e) Waibel, M.; Cramer, N. Angew. Chem., Int. Ed. 2010, 49, 4455−4458. (f) Waibel, M.; Cramer, N. Chem. Commun. 2011, 47, 346−348. (g) Wang, Y.; Kang, Q. Org. Lett. 2014, 16, 4190−4193. (h) Sun, G.-J.; Wang, Y.; Kang, Q. Synthesis 2015, 47, 2931−2936. (13) (a) Nečas, D.; Turský, M.; Kotora, M. J. Am. Chem. Soc. 2004, 126, 10222−10223. (b) Nečas, D.; Turský, M.; Tišlerová, I.; Kotora, M. New J. Chem. 2006, 30, 671−674. (c) Turský, M.; Nečas, D.; Drabina, P.; Sedlák, M.; Kotora, M. Organometallics 2006, 25, 901− 907. (d) Nečas, D.; Drabina, P.; Sedlák, M.; Kotora, M. Tetrahedron Lett. 2007, 48, 4539−4541. (e) Nečas, D.; Kotora, M. Org. Lett. 2008, 10, 5261−5263. (f) Fisher, E. L.; Lambert, T. H. Org. Lett. 2009, 11, 4108−4110. (g) Sumida, Y.; Yorimitsu, H.; Oshima, K. Org. Lett. 2010, 12, 2254−2257. (14) Transformations of allylbenzene derivatives through oxidative cleavage of allylic C−C bonds have been reported, but regioselectivity of the cleaved bonds highly depends on the substituent pattern of aromatic rings: (a) Chen, F.; Qin, C.; Cui, Y.; Jiao, N. Angew. Chem., Int. Ed. 2011, 50, 11487−11491. (b) Qin, C.; Zhou, W.; Chen, F.; Ou, Y.; Jiao, N. Angew. Chem., Int. Ed. 2011, 50, 12595−12599. (c) Liu, J.; Wen, X.; Qin, C.; Li, X.; Luo, X.; Sun, A.; Zhu, B.; Song, S.; Jiao, N. Angew. Chem., Int. Ed. 2017, 56, 11940−11944. (15) The reaction of 1e with an aliphatic alkene such as vinylcyclohexane proceeded less efficiently and provided a mixture of alkenylation and allylation products. Therefore, the resulting mixture was hydrogenated, and the corresponding 2-cyclohexylethylation product was obtained in 52% GC yield. See the Supporting Information for details. (16) For examples of pyrazole-directed functionalization: (a) Umeda, N.; Tsurugi, H.; Satoh, T.; Miura, M. Angew. Chem., Int. Ed. 2008, 47, 4019−4022. (b) Arockiam, P. B.; Fischmeister, C.; Bruneau, C.; Dixneuf, P. H. Green Chem. 2011, 13, 3075−3078. (c) Yu, X.; Yu, S.; Xiao, J.; Wan, B.; Li, X. J. Org. Chem. 2013, 78, 5444−5452. (d) Thirunavukkarasu, V. S.; Raghuvanshi, K.; Ackermann, L. Org. Lett. 2013, 15, 3286−3289. (e) Boerth, J. A.; Hummel, J. R.; Ellman, J. A. Angew. Chem., Int. Ed. 2016, 55, 12650−12654. (f) Gulia, N.; Daugulis, O. Angew. Chem., Int. Ed. 2017, 56, 3630−3634. (17) Syntheses of Cp*Rh−hydride complexes by reaction with alcohol solvents: (a) White, C.; Oliver, A. J.; Maitlis, P. M. J. Chem. Soc., Dalton Trans. 1973, 18, 1901−1907. (b) Nutton, A.; Bailey, P. M.; Maitlis, P. M. J. Organomet. Chem. 1981, 213, 313−332. A Cp*Rh−hydride complex, which is formed by oxidation of methanol, is considered to be an active species in the α-methylation of ketones: (c) Chan, L. K. M.; Poole, D. L.; Shen, D.; Healy, M. P.; Donohoe, T. J. Angew. Chem., Int. Ed. 2014, 53, 761−765. (18) Although we did not have certain evidence of a rhodium− hydride complex existing in the catalytic cycle, trace amounts of double bond isomerization products derived from allylbenzene derivatives were often detected by GC-MS analysis of the crude reaction mixture

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/jacs.8b03718. Full experimental details and characterization data (PDF)

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AUTHOR INFORMATION

Corresponding Author

*[email protected] ORCID

Takuya Kochi: 0000-0002-5491-0566 Fumitoshi Kakiuchi: 0000-0003-2605-4675 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported in part by JSPS KAKENHI Grant Numbers 17K19126, 16H04150, and 15H05839 (Middle Molecular Strategy). T.K. is also grateful for support by JSPS KAKENHI Grant Numbers 16H01040 and 18H04271 (Precisely Designed Catalysts with Customized Scaffolding). S.O. is also grateful for support by the Research Grant of Keio Leading-edge Laboratory of Science & Technology.

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DOI: 10.1021/jacs.8b03718 J. Am. Chem. Soc. 2018, 140, 9788−9792