Abstract
Benzoic acids are highly important structural motifs in drug molecules and natural products. Selective C–H bond functionalization of benzoic acids will provide synthetically useful tools for step-economical organic synthesis. Although direct ortho-C–H functionalizations of benzoic acids or their derivatives have been intensely studied, the ability to activate meta-C–H bond of benzoic acids or their derivatives in a general manner via transition-metal catalysis has been largely unsuccessful. Although chelation-assisted meta-C–H functionalization of electron-rich arenes was reported, chelation-assisted meta-C–H activation of electron-poor arenes such as benzoic acid derivatives remains a formidable challenge. Herein, we report a general protocol for meta-C–H olefination of benzoic acid derivatives using a nitrile-based sulfonamide template. A broad range of benzoic acid derivatives are meta-selectively olefinated using molecular oxygen as the terminal oxidant. The meta-C–H acetoxylation, product of which is further transformed at the meta-position, is also reported.
Introduction
Benzoic acids are highly valuable structural motifs and precursors for synthesizing other organic substances. Direct and selective transformation of the C–H bonds of this class of compounds would be very attractive for developing step-economical organic syntheses (Fig. 1)1,2,3,4,5,6,7,8,9,10,11,12,13,14. To date, direct ortho-C–H functionalizations of benzoic acids or their derivatives have been intensely studied with transition-metal catalysts1,2,3,4,5,6,7,8,9,10,11,12 or by directed ortho metalation13. Traditionally, the meta-position of benzoic acids were functionalized by electrophilic aromatic substitution, which often requires harsh conditions as benzoic acids are generally deactivated towards this reaction14. Transition-metal catalysts have been used to functionalize meta-C–H bonds of limited benzoic acid derivatives. Hartwig, Yu, Sanford and others have achieved modest to high selectivity because of substrate steric or electronic control15,16,17,18,19,20,21,22,23,24,25. In prior examples, an excess of the benzoic acid derivative, which was often used as the solvent, was generally required with a Pd catalyst (Fig. 1a)17,18,21. Despite these highly important pioneering studies, the ability to activate the meta-C–H bond of benzoic acids or their derivatives in a general manner via transition-metal catalysis has been largely unsuccessful25. Therefore, a general approach to meta-C–H functionalization of benzoic acids or their derivatives regardless of the substitution patterns is highly desirable to provide synthetic short-cuts.
(a) Previous reports on meta-C–H functionalizations of limited benzoic acid derivatives. (b) Our design of template for meta-C–H functionalizations of electron-poor benzoic acid derivatives and the highlights of our work. (c) Representative drugs of benzoic acid derivatives with meta-substituents.
Controlling the site-selectivity of C–H activation reactions is an outstanding challenge in the development syntheticially useful C–H functinalization methodology26,27. So far only a limited number of approaches are available for addressing meta-C–H functionalizations of arenes28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63. These approaches include inherent substrate control via steric and/or electronic factors28,29,30,31,32,33,34,35, chelating group-assisted Cu(II)-catalysed arylation36,37, ruthenium(II) complex facilitated meta-C–H functionalizations38,39,40,41,42,43, the use of transient norbornene mediator44,45 and formal meta-C–H functionalizations utilizing traceless directing groups46,47,48,49,50,51. Another unique method is the use of nitrile-based templates for meta-C–H functionalizations of electron-rich arenes, such as hydrocinnamic acids and phenylacetic acids, which was pioneered by the group of Yu54,55,56,57,58,59,60,61,62,63. However, chelation-assisted meta-C–H activation of electron-poor arenes such as benzoic acid derivatives remains a formidable challenge, possibly due to the low reactivity of the electron-poor arenes towards palladation in this type of C–H activation.
Herein, we disclose our discovery of a recyclable nitrile-based sulfonamide template that promotes the olefination and acetoxylation of meta-C–H bonds of a broad range of benzoic acid derivatives (Fig. 1b). Notably, a protocol is developed that enables the use of environmentally benign molecular oxygen as the terminal oxidant for chelation-assisted meta-C–H olefination, which previously required the use of costly silver salt oxidants.
Results
Development of meta-C–H olefination reaction conditions
As benzoic acids are both electronically and structurally distinct from other electron-rich arenes that undergo template-assisted meta-C–H functinalizations, the elaboration of a compatible template-directing group is required to accommodate their unique properties. After investigating several newly designed templates (see Supplementary Table 1 for details), we found amide 1a bearing a highly electron-withdrawing nosyl group was the most promising substrate. After 1a was subjected to the similar reaction conditions that were developed by us for meta-C–H olefination64,65,66,67 of phenylethylamines63, much to our delight, excellent yields of desired products were obtained with tiny traces of other olefinated isomers (Table 1, entry 1). To avoid using the costly silver acetate as the oxidant, we continued to optimize the reaction conditions to search for a less costly oxidant. After screening a few inorganic as well as organic oxidants (entries 2–5), we were very surprised to find Cu(OAc)2, which might compete with Pd(OAc)2 in coordination with the weakly coordinating nitrile group, could be used as an effective oxidant (entry 2). The yield was increased to 72% when the reaction was run under oxygen atmosphere (entry 6)10,68,69. Notably, better results were obtained by increasing the loading of Ac-Gly-OH ligand (entries 7–8), leading to almost full conversion of the substrate with 60 mol% of the ligand (entry 8). By further tuning the loading of Cu(OAc)2, the reaction time and temperature (entries 9–13), the best result was achieved in 48 h at 90 °C using oxygen as the terminal oxidant with catalytic amount of Cu(OAc)2 (entry 13). It was found that the reaction was almost shut down without adding Cu(OAc)2 as co-oxidant (entry 12). The use of oxygen is notable as all the previous chelation-assisted meta-C–H olefination reactions required the use of silver salt as the oxidant54,55,56,57,58,59,60,61,62,63. Finally, the reaction conditions were carefully tuned to improve the mono versus di-olefination selectivity (see also Supplementary Table 1 for details), although the two products could be easily separated. Pleasingly, the use of Formyl-Gly-OH ligand with an inorganic base would result in good mono versus di-olefination selectivities (entries 14–15)59, albeit in lower overall yield. Interestingly, this selectivity was switched when no inorganic base was added (entry 16).
Substrate scope of meta-C–H olefination
With the optimized conditions in hand, we carried out olefinations on a variety of benzoic acid derivatives, which were easily prepared in one step from benzoic acids using routine conditions (see Supplementary Methods for details). It was found that both electron-donating and electron-withdrawing ortho-substituents were well tolerated (Fig. 2a, 3b–3e), and a good yield of mono-olefinated product was obtained with substrate 1b. Di-olefination occurred predominantly with less hindered amides 1c–1e. Notably, our method provided a direct access to an aspirin derivative (3e). The reaction also proceeded smoothly with meta-substituted substrates (3f–3h). Para-substituted benzamides with electron-donating methoxy (3i) and methyl (3j) groups as well as electron-withdrawing fluoro (3k), chloro (3l) and bromo (3m) groups were all suitable substrates, affording mono-olefinated products selectively. Interesting, the bromo group (3m) was tolerated in our protocol, which is synthetically useful for further elaborations of the product. It should be noted di-olefination products with high overall yields could also be produced when KH2PO4 was used as the base for substrates 1j–1l (see Supplementary Methods for details). Importantly, the method was compatible with a range of substrates carrying two substituents (3n–3w), generally producing high yields of desired products. It is surprising that tri-substituted substrates were also able to afford desired products in moderate to high yields (3x–3z). Such highly substituted patterns were not observed in all previous transition-metal catalysed meta-C–H functionalizations. Desired products were also generated with other electron-deficient olefin-coupling partners (3fa–3fe), although production of 3fc and 3fd required silver acetate as the oxidant since the standard conditions only afforded low yields of these two products. The meta-selectivity was generally excellent, although traces of isomers were observed for some substrates. However, it was hard to assign the peaks of isomers that were only traces from the crude 1H NMR and thus we did not attempt to calculate the exact ratios of isomers. Finally, the template-directing group could be removed and recycled readily with LiOH or K2CO3 in high yields as shown in Fig. 2b. Moreover, the auxiliary 5 could be synthesized in multi-gram scale from inexpensive chemicals (see Supplementary Methods for details).
(a) Substrate scope of meta-C–H olefination. Reaction conditions: 1 (0.1–0.2 mmol), 2 (2.0 equiv), Pd(OAc)2 (10 mol%), Ac-Gly-OH (60–100 mol%), Cu(OAc)2 (0.2–1.0 equiv), O2 (1 atm), HFIP (1–2 ml), 80–90 °C, 24–48 h, see the Supplementary Methods for details. Isolated yields are reported. aFormyl-Gly-OH (60 mol%) was used instead of Ac-Gly-OH. bKH2PO4 (0.5 equiv) was added. cA trace of (m,m')-diolefinated product was observed. dK2HPO4 (0.5 equiv) was added. eAgOAc (3.0 equiv) was used instead of O2/Cu(OAc)2. (b) Two mild methods available for regenerating auxiliary 5.
Meta-C–H acetoxylation
The versatility of our sulfonamide template with different catalytic cycles was investigated briefly with meta-acetoxylation of benzoic acid derivatives using the previously established oxidation conditions (Fig. 3a)70. Although the acetoxylation was generally less efficient than olefination, several substrates with different substitution patterns underwent meta-acetoxylation successfully to give desired products in moderate to good yields (6a–6za). Moreover, 60% combined yield of products was obtained when the reaction was performed in 1.3 mmol scale (6a).
(a) Meta-C–H acetoxylation. Reaction conditions: 1 (0.1 mmol), Pd(OAc)2 (10 mol%), Ac-Gly-OH (20 mol%), Ac2O (5.0 equiv), PhI(OAc)2 (3.0 equiv), HFIP (1 ml), N2, 90 °C, 24 h. Isolated yields are reported; see the Supplementary Methods for details. aA trace of regioisomer was observed. bThe yield was 60% (mono/di: 4.8:1) in 1.3 mmol scale. c6 h. dA trace of (m,m')-di-acetoxylated product was observed. (b) Application potential of meta-acetoxylation demonstrated with further elaborations.
Synthetic elaboration
To demonstrate the utility of our meta-C–H functionalizations, we attempted further elaboration of the acetoxylated product (Fig. 3b). Thus, triflate 7 was prepared in high yield from 6amono by hydrolysis of the template and the acetoxy group in one step, which was followed by triflation of the resulting hydroxyl group. Triflate 7 was then transformed to a range of synthetically useful substances with well-established coupling reactions, namely, amination (8), arylation (9), alkynylation (10), cyanation (11) and carbonylation (12), greatly expanding the application potential of our method.
Proposed catalytic cycle
On the basis of the above results, a plausible catalytic cycle is proposed for meta-C–H olefination (Fig. 4). The complex A is generated by coordination of substrate 1 to a Pd(II) species followed by template-directed insertion of Pd(II) into the meta-C–H bond of 1. Following coordination of A with olefin 2, the resulting complex B undergoes 1,2-migratory insertion to give intermediate C. Product 3 is then afforded by β-hydride elimination of C. Reductive elimination of hydride D produces Pd(0), which is reoxidized to Pd(II) by two equivalents of Cu(II). The resulting Cu(I) is then oxidized by molecular oxygen to re-enter the catalytic cycle.
The plausible mechanism involves regeneration of a Pd(II) catalyst with only catalytic amount of Cu(II) species.
Discussion
In summary, a general protocol for meta-C–H bond olefination of a broad range of benzoic acid derivatives assisted by a nitrile-based sulfonamide template has been developed. Desired meta-functionalized products were obtained regardless of the substitution patterns and steric biases of the substrates. Notably, the challenging tri-substituted substrates were tolerated, which was not observed in previous transition-metal catalysed meta-C–H functionalizations15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63. Importantly, the new protocol was compatible with molecular oxygen as the terminal oxidant. Moreover, the sulfonamide template auxiliary could be efficiently removed and recycled under mild conditions. Finally, the versatility of our template was demonstrated with meta-C–H acetoxylation, which enabled the access to five synthetically useful major classes of substitents at the meta-position of benzoic acid derivatives. It is expected that the protocol disclosed herein will soon inspire the development of more synthetically useful meta-C–H transformations for benzoic acid derivatives.
Methods
General methods
For 1H and 13C NMR spectra of compounds in this manuscript and details of the synthetic procedures, see Supplementary Figs 1–102 and Supplementary Methods.
General procedure for meta-C–H olefination
To a 50-ml Schlenk sealed tube (with a Teflon cap) equipped with a magnetic stir bar was charged with amide 1 (0.10 mmol, 1.0 equiv), Pd(OAc)2 (2.3 mg, 0.010 mmol, 10 mol%), Ac-Gly-OH (20–100 mol%) and Cu(OAc)2 (0.2–1.0 equiv) sequentially. Hexafluoro-2-propanol (HFIP; 1.0 ml) was added to the mixture along the inside wall of the tube, followed by the corresponding alkene 2 (2.0 equiv). The reaction tube was capped, then evacuated briefly under vacuum and charged with O2 (1 atm, balloon, × 3). The tube was then submerged into a preheated 80 or 90 °C oil bath. The reaction was stirred for 24–48 h and cooled to room temperature. The crude reaction mixture was diluted with EtOAc (5 ml) and filtered through a short pad of Celite. The sealed tube and Celite pad were washed with an additional 20 ml of EtOAc. The filtrate was concentrated in vacuo, and the resulting residue was purified by flash silica gel chromatography or preparative thin layer chromatography using petroleum ether/EtOAc as the eluent. The site selectivity was assigned by NMR analysis of the product or the hydrolysed product. Full experimental details and characterization of new compounds can be found in the Supplementary Methods.
General procedure for meta-C–H acetoxylation
To a 50-ml Schlenk sealed tube (with a Teflon cap) equipped with a magnetic stir bar was charged with amide 1 (0.10 mmol, 1.0 equiv), Pd(OAc)2 (2.3 mg, 0.010 mmol, 10 mol%), Ac-Gly-OH (2.4 mg, 0.020 mmol, 20 mol%) and PhI(OAc)2 (96.6 mg, 0.30 mmol, 3 equiv). HFIP (1.0 ml) was added to the mixture along the inside wall of the tube, followed by Ac2O (47 μl, 5 equiv). The reaction tube was capped, then evacuated briefly under vacuum and charged with N2 (1 atm, balloon, × 3). The tube was then submerged into a preheated 90 °C oil bath. The reaction was stirred for 24 h and cooled to room temperature. The crude reaction mixture was diluted with EtOAc (5 ml) and filtered through a short pad of Celite. The sealed tube and Celite pad were washed with an additional 20 ml of EtOAc. The filtrate was concentrated in vacuo, and the resulting residue was purified by flash silica gel chromatography using petroleum ether/EtOAc as the eluent. Full experimental details and characterization of new compounds can be found in the Supplementary Methods.
Additional information
How to cite this article: Li, S. et al. Pd(II)-catalysed meta-C–H functionalizations of benzoic acid derivatives. Nat. Commun. 7:10443 doi: 10.1038/ncomms10443 (2016).
References
Lyons, T. W. & Sanford, M. S. Palladium-catalyzed ligand-directed C–H functionalization reactions. Chem. Rev. 110, 1147–1169 (2010).
Hartwig, J. F. Borylation and silylation of C–H bonds: a platform for diverse C–H bond functionalizations. Acc. Chem. Res. 45, 864–873 (2011).
Engle, K. M., Mei, T.-S., Wasa, M. & Yu, J.-Q. Weak coordination as a powerful means for developing broadly useful C–H functionalization reactions. Acc. Chem. Res. 45, 788–802 (2012).
Patureau, F. W., Wencel-Delord, J. & Glorius, F. Cp*Rh-catalyzed C–H activations: Versatile dehydrogenative cross-couplings of CSP2 C–H positions with olefins, alkynes, and arenes. Aldrichimica Acta 45, 31–41 (2012).
Rouquet, G. & Chatani, N. Catalytic functionalization of C(sp2)–H and C(sp3)–H bonds by using bidentate directing groups. Angew. Chem. Int. Ed. 52, 11726–11743 (2013).
Ackermann, L. Carboxylate-assisted ruthenium-catalyzed alkyne annulations by C–H/Het–H bond functionalizations. Acc. Chem. Res. 47, 281–295 (2014).
Zhang, X.-S., Chen, K. & Shi, Z.-J. Transition metal-catalyzed direct nucleophilic addition of C–H bonds to carbon–heteroatom double bonds. Chem. Sci 5, 2146–2159 (2014).
Daugulis, O., Roane, J. & Tran, L. D. Bidentate, monoanionic auxiliary-directed functionalization of carbon–hydrogen bonds. Acc. Chem. Res. 48, 1053–1064 (2015).
Satoh, T. & Miura, M. Transition-metal-catalyzed regioselective arylation and vinylation of carboxylic acids. Synthesis (Mass) 2010, 3395–3409 (2010).
Miura, M., Tsuda, T., Satoh, T., Pivsa-Art, S. & Nomura, M. Oxidative cross-coupling of N-(2'-Phenylphenyl)benzene- sulfonamides or benzoic and naphthoic acids with alkenes using a palladium−copper catalyst system under air. J. Org. Chem. 63, 5211–5215 (1998).
Giri, R. et al. Palladium-catalyzed methylation and arylation of sp2 and sp3 C−H bonds in simple carboxylic acids. J. Am. Chem. Soc. 129, 3510–3511 (2007).
Chiong, H. A., Pham, Q.-N. & Daugulis, O. Two methods for direct ortho-arylation of benzoic acids. J. Am. Chem. Soc. 129, 9879–9884 (2007).
Hartung, C. G. & Snieckus, V. in Modern Arene Chemistry ed. Astruc D. 330–367Wiley-VCH (2002).
Taylor, R. Electrophilic Aromatic Substitution Wiley (1990).
Cho, J.-Y., Tse, M. K., Holmes, D., Maleczka, R. E. & Smith, M. R. Remarkably selective iridium catalysts for the elaboration of aromatic C–H bonds. Science 295, 305–308 (2002).
Ishiyama, T., Takagi, J., Hartwig, J. F. & Miyaura, N. A stoichiometric aromatic C–H borylation catalyzed by iridium(I)/2,2'-bipyridine complexes at room temperature. Angew. Chem. Int. Ed. 41, 3056–3058 (2002).
Zhang, Y.-H., Shi, B.-F. & Yu, J.-Q. Pd(II)-catalyzed olefination of electron-deficient arenes using 2,6-dialkylpyridine ligands. J. Am. Chem. Soc. 131, 5072–5074 (2009).
Emmert, M. H., Cook, A. K., Xie, Y. J. & Sanford, M. S. Remarkably high reactivity of Pd(OAc)2/pyridine catalysts: nondirected C–H oxygenation of arenes. Angew. Chem. Int. Ed. 50, 9409–9412 (2011).
Ball, L. T., Lloyd-Jones, G. C. & Russell, C. A. Gold-catalyzed direct arylation. Science 337, 1644–1648 (2012).
Wencel-Delord, J., Nimphius, C., Wang, H. & Glorius, F. Rhodium(III) and hexabromobenzene – A catalyst system for the cross-dehydrogenative coupling of simple arenes and heterocycles with arenes bearing directing groups. Angew. Chem. Int. Ed. 51, 13001–13005 (2012).
Shrestha, R., Mukherjee, P., Tan, Y., Litman, Z. C. & Hartwig, J. F. Sterically controlled, palladium-catalyzed intermolecular amination of arenes. J. Am. Chem. Soc. 135, 8480–8483 (2013).
Boursalian, G. B., Ngai, M.-Y., Hojczyk, K. N. & Ritter, T. Pd-catalyzed aryl C–H imidation with arene as the limiting reagent. J. Am. Chem. Soc. 135, 13278–13281 (2013).
Cong, X., Tang, H., Wu, C. & Zeng, X. Role of mono-N-protected amino acid ligands in palladium(II)-catalyzed dehydrogenative Heck reactions of electron-deficient (hetero)arenes: Experimental and computational studies. Organometallics 32, 6565–6575 (2013).
Cheng, C. & Hartwig, J. F. Rhodium-catalyzed intermolecular C–H silylation of arenes with high steric regiocontrol. Science 343, 853–857 (2014).
Kuninobu, Y., Ida, H., Nishi, M. & Kanai, M. A meta-selective C–H borylation directed by a secondary interaction between ligand and substrate. Nat. Chem 7, 712–717 (2015).
Yang, J. Transition metal catalyzed meta-C-H functionalization of aromatic compounds. Org. Biomol. Chem. 13, 1930–1941 (2015).
Li, J., Sarkar, S. D. & Ackermann, L. meta- and para-Selective C–H Functionalization by C–H Activation. Top. Organomet. Chem. 55, 217–257 (2016).
Ishiyama, T. et al. Mild iridium-catalyzed borylation of arenes. High turnover numbers, room temperature reactions, and isolation of a potential intermediate. J. Am. Chem. Soc. 124, 390–391 (2002).
Hull, K. L. & Sanford, M. S. Catalytic and highly regioselective cross-coupling of aromatic C−H substrates. J. Am. Chem. Soc. 129, 11904–11905 (2007).
Lyons, T. W., Hull, K. L. & Sanford, M. S. Controlling site selectivity in Pd-catalyzed oxidative cross-coupling reactions. J. Am. Chem. Soc. 133, 4455–4464 (2011).
Patureau, F. W., Nimphius, C. & Glorius, F. Rh catalyzed C–H activation and oxidative olefination without chelate assistance: on the reactivity of bromoarenes. Org. Lett. 13, 6346–6349 (2011).
Wencel-Delord, J., Nimphius, C., Patureau, F. W. & Glorius, F. [RhIIICp*]-catalyzed dehydrogenative aryl–aryl bond formation. Angew. Chem. Int. Ed. 51, 2247–2251 (2012).
Ye, M., Gao, G.-L. & Yu, J.-Q. Ligand-promoted C-3 selective C–H olefination of pyridines with Pd catalysts. J. Am. Chem. Soc. 133, 6964–6967 (2011).
Li, B.-J. & Shi, Z.-J. Ir-catalyzed highly selective addition of pyridyl C–H bonds to aldehydes promoted by triethylsilane. Chem. Sci 2, 488–493 (2011).
Zhou, L. & Lu, W. Palladium(II)-catalyzed coupling of electron-deficient arenes via C–H activation. Organometallics 31, 2124–2127 (2012).
Phipps, R. J. & Gaunt, M. J. A meta-selective copper-catalyzed C–H bond arylation. Science 323, 1593–1597 (2009).
Duong, H. A., Gilligan, R. E., Cooke, M. L., Phipps, R. J. & Gaunt, M. J. Copper(II)-catalyzed meta-selective direct arylation of α-aryl carbonyl compounds. Angew. Chem. Int. Ed. 50, 463–466 (2011).
Ackermann, L., Hofmann, N. & Vicente, R. Carboxylate-assisted ruthenium-catalyzed direct alkylations of ketimines. Org. Lett. 13, 1875–1877 (2011).
Saidi, O. et al. Ruthenium-catalyzed meta sulfonation of 2-phenylpyridines. J. Am. Chem. Soc. 133, 19298–19301 (2011).
Hofmann, N. & Ackermann, L. meta-Selective C–H bond alkylation with secondary alkyl halides. J. Am. Chem. Soc. 135, 5877–5884 (2013).
Paterson, A. J. St, John-Campbell, S., Mahon, M. F., Press, N. J. & Frost, C. G. Catalytic meta-selective C–H functionalisation to construct quaternary carbon centres. Chem. Commun. 51, 12807–12810 (2015).
Teskey, C. J., Lui, A. Y. W. & Greaney, M. F. Ruthenium-catalyzed meta-selective C–H bromination. Angew. Chem. Int. Ed. 54, 11677–11680 (2015).
Li, J. et al. N-acyl amino acid ligands for ruthenium(II)-catalyzed meta-C–H tert-alkylation with removable auxiliaries. J. Am. Chem. Soc. 137, 13894–13901 (2015).
Wang, X.-C. et al. Ligand-enabled meta-C–H activation using a transient mediator. Nature 519, 334–338 (2015).
Dong, Z., Wang, J. & Dong, G. Simple amine-directed meta-selective C–H arylation via Pd/norbornene catalysis. J. Am. Chem. Soc. 137, 5887–5890 (2015).
Mochida, S., Hirano, K., Satoh, T. & Miura, M. Synthesis of stilbene and distyrylbenzene derivatives through rhodium-catalyzed ortho-olefination and decarboxylation of benzoic acids. Org. Lett. 12, 5776–5779 (2010).
Cornella, J., Righi, M. & Larrosa, I. Carboxylic acids as traceless directing groups for formal meta-selective direct arylation. Angew. Chem. Int. Ed. 50, 9429–9432 (2011).
Luo, J., Preciado, S. & Larrosa, I. Overriding ortho–para selectivity via a traceless directing group relay strategy: the meta-selective arylation of phenols. J. Am. Chem. Soc. 136, 4109–4112 (2014).
Zhang, Y., Zhao, H., Zhang, M. & Su, W. Carboxylic acids as traceless directing groups for the rhodium(III)-catalyzed decarboxylative C–H arylation of thiophenes. Angew. Chem. Int. Ed. 54, 3817–3821 (2015).
Lee, D. & Chang, S. Direct C–H amidation of benzoic acids to introduce meta- and para-amino groups by tandem decarboxylation. Chem. Eur. J 21, 5364–5368 (2015).
Shi, X.-Y. et al. A convenient synthesis of N-aryl benzamides by rhodium-catalyzed ortho-amidation and decarboxylation of benzoic acids. Chem. Eur. J 21, 1900–1903 (2015).
Zhang, J. et al. Palladium(II)-catalyzed meta-selective direct arylation of O-β-naphthyl carbamate. Chem. Commun 51, 1297–1300 (2015).
Martinez-Martinez, A. J., Kennedy, A. R., Mulvey, R. E. & O'Hara, C. T. Directed ortho-meta'- and meta-meta'-dimetalations: A template base approach to deprotonation. Science 346, 834–837 (2014).
Leow, D., Li, G., Mei, T.-S. & Yu, J.-Q. Activation of remote meta-C–H bonds assisted by an end-on template. Nature 486, 518–522 (2012).
Dai, H.-X., Li, G., Zhang, X.-G., Stepan, A. F. & Yu, J.-Q. Pd(II)-catalyzed ortho- or meta-C–H olefination of phenol derivatives. J. Am. Chem. Soc. 135, 7567–7571 (2013).
Wan, L., Dastbaravardeh, N., Li, G. & Yu, J.-Q. Cross-coupling of remote meta-C–H bonds directed by a U-shaped template. J. Am. Chem. Soc. 135, 18056–18059 (2013).
Tang, R.-Y., Li, G. & Yu, J.-Q. Conformation-induced remote meta-C–H activation of amines. Nature 507, 215–220 (2014).
Yang, G. et al. Pd(II)-catalyzed meta-C-H olefination, arylation, and acetoxylation of indolines using a U-shaped template. J. Am. Chem. Soc. 136, 10807–10813 (2014).
Deng, Y. & Yu, J.-Q. Remote meta-C–H olefination of phenylacetic acids directed by a versatile U-shaped template. Angew. Chem. Int. Ed. 54, 888–891 (2015).
Lee, S., Lee, H. & Tan, K. L. meta-Selective C–H functionalization using a nitrile-based directing group and cleavable Si-tether. J. Am. Chem. Soc. 135, 18778–18781 (2013).
Bera, M., Modak, A., Patra, T., Maji, A. & Maiti, D. meta-Selective arene C–H bond olefination of arylacetic acid using a nitrile-based directing group. Org. Lett. 16, 5760–5763 (2014).
Bera, M., Maji, A., Sahoo, S. K. & Maiti, D. Palladium(II)-catalyzed meta-C–H olefination: Constructing multisubstituted arenes through homo-diolefination and sequential hetero-diolefination. Angew. Chem. Int. Ed. 54, 8515–8519 (2015).
Li, S., Ji, H., Cai, L. & Li, G. Pd(II)-catalyzed remote regiodivergent ortho- and meta-C–H functionalisations of phenylethylamines. Chem. Sci 6, 5595–5600 (2015).
Jia, C., Kitamura, T. & Fujiwara, Y. Catalytic functionalization of arenes and alkanes via C−H bond activation. Acc. Chem. Res. 34, 633–639 (2001).
Satoh, T. & Miura, M. Oxidative coupling of aromatic substrates with alkynes and alkenes under rhodium catalysis. Chem. Eur. J 16, 11212–11222 (2010).
Yeung, C. S. & Dong, V. M. Catalytic dehydrogenative cross-coupling: forming carbon−carbon bonds by oxidizing two carbon−hydrogen bonds. Chem. Rev. 111, 1215–1292 (2011).
Le Bras, J. & Muzart, J. Intermolecular dehydrogenative Heck reactions. Chem. Rev. 111, 1170–1214 (2011).
Wang, D.-H., Engle, K. M., Shi, B.-F. & Yu, J.-Q. Ligand-enabled reactivity and selectivity in a synthetically versatile aryl C–H olefination. Science 327, 315–319 (2010).
Liu, B., Jiang, H.-Z. & Shi, B.-F. Palladium-catalyzed oxidative olefination of phenols bearing removable directing groups under molecular oxygen. J. Org. Chem. 79, 1521–1526 (2014).
Dick, A. R., Hull, K. L. & Sanford, M. S. A highly selective catalytic method for the oxidative functionalization of C–H bonds. J. Am. Chem. Soc. 126, 2300–2301 (2004).
Acknowledgements
We gratefully acknowledge NSFC (21402198), ‘The 1000 Youth Talents Program’, and FJIRSM for financial support.
Author information
Authors and Affiliations
Contributions
S.L., L.C. and H.J. performed the experiments and developed the reactions. L.Y. helped collecting some experimental data. G.L. designed and directed the project and wrote the manuscript with the feedback of S.L., L.C and H.J.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary Information
Supplementary Figures 1-102, Supplementary Table 1, Supplementary Methods and Supplementary References (PDF 9955 kb)
Rights and permissions
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
About this article
Cite this article
Li, S., Cai, L., Ji, H. et al. Pd(II)-catalysed meta-C–H functionalizations of benzoic acid derivatives. Nat Commun 7, 10443 (2016). https://doi.org/10.1038/ncomms10443
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/ncomms10443
This article is cited by
-
Effects of cobalt oxide catalyst on pyrolysis of polyester fiber
Korean Journal of Chemical Engineering (2022)
-
H-bonded reusable template assisted para-selective ketonisation using soft electrophilic vinyl ethers
Nature Communications (2018)
-
Ruthenium(II)-catalysed remote C–H alkylations as a versatile platform to meta-decorated arenes
Nature Communications (2017)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
