Communication pubs.acs.org/JACS
Cite This: J. Am. Chem. Soc. 2018, 140, 586−589
Directed Decarbonylation of Unstrained Aryl Ketones via NickelCatalyzed CC Bond Cleavage Tian-Tian Zhao,†,§ Wen-Hua Xu,†,§ Zhao-Jing Zheng,‡ Peng-Fei Xu,*,‡ and Hao Wei*,† †
Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry & Materials Science, Northwest University, Xi’an 710069, China ‡ State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China S Supporting Information *
Table 1. Optimization of the Reaction Conditionsa
ABSTRACT: The nickel-catalyzed decarbonylation of unstrained diaryl ketones has been developed. The reaction is catalyzed by a combination of Ni(cod)2 and an electron-rich N-heterocyclic carbene ligand. High functional group tolerance and excellent yields (up to 98%) are observed. This strategy provides an alternative and versatile approach to construct biaryls using an inexpensive nickel catalyst.
D
ue to the presence of biaryl structures, especially those containing an indole nucleus, in the vast majority of medicinally relevant synthetic targets, the development of efficient, selective, and sustainable technologies for constructing these organic structures is of critical importance.1 Transitionmetal-catalyzed decarbonylation of diaryl ketones offers a completely new means to construct biaryl structures with excellent step and atom economy (Scheme 1a). However, this method has proved to be of limited success given the chemical inertness of carbon−carbon linkages.2 Because catalytic CC bond activation is an important challenge in modern chemistry,3 exploiting a CC bond as a functional group not only provides a new perspective for chemists but also represents a powerful and straightforward strategy for
a Standard conditions: 1a (0.1 mmol), Ni(cod)2 (10 mol %), IMes· HCl (20 mol %), Cs2CO3 (0.5 equiv), dioxane (1.5 mL) at 150 °C, 24 h. bYields were determined by 1H NMR spectroscopy using 1,1,2,2tetrachloroethane as an internal standard.
Scheme 1. Metal Complex-Mediated Decarbonylation of Unstrained Biaryl Ketones
constructing chemical bonds through a new pathway.4 The first example of the decarbonylation of diaryl ketones was reported in 2004 by Brookhart et al., 5 who used a stoichiometric amount of a rhodium mediator in an intramolecular reaction to form biaryl structures. In 2012, Shi reported the decarbonylation of diaryl ketones, bearing a directing group (DG), through the use of another rhodium catalyst.6 However, both processes depend on the use of precious rhodium complexes.7 Compared with other transition metals, Ni-complex offers a unique platform which usually exhibits exceptionally high reactivity and a distinct pattern of selectivity. Their potential to Received: October 31, 2017 Published: January 5, 2018 © 2018 American Chemical Society
586
DOI: 10.1021/jacs.7b11591 J. Am. Chem. Soc. 2018, 140, 586−589
Communication
Journal of the American Chemical Society
Table 3. Scope of Ni-Catalyzed Decarbonylationa,b
Scheme 2. Screening of the Directing Groups
Table 2. Scope of Aromatic Substituents in Ni Catalyzed Decarbonylationa,b
a
Standard conditions: 4 or 6 (0.1 mmol), Ni(cod)2 (10 mol %), IMes•HCl (20 mol %), Cs2CO3 (0.5 equiv), dioxane (1.5 mL) at 150 °C, 24 h. bIsolated yields.
Scheme 3. Possible Mechanism
a
Standard conditions: 1 (0.1 mmol), Ni(cod)2 (10 mol %), IMes•HCl (20 mol %), Cs2CO3 (0.5 equiv), dioxane (1.5 mL) 150 °C, 24 h. bAll yields are isolated yields
activate inert chemical bonds, such as CO, CF, CN and CH bonds, has been demonstrated by many reports.8 Recently, Chatani et al. reported the decarbonylation of diaryl ketones by using a stoichiometric amount of the nickel complex.9 This report suggested that using a nickel complex was a promising approach for achieving CC bond activation. To realize nickel-catalyzed decarbonylation, it is envisioned that the nickel carbonyl species would be trapped by a strong coordination group to form a stable cyclic intermediate, which would promote the release of carbon monoxide from the coordination sphere of the nickel (Scheme 1b). The merits of this coordination approach are 3-fold: (1) a stoichiometric amount of the nickel complex would be unnecessary, allowing for a catalytic decarbonylation; (2) the coordination group would also be used as a directing group to achieve the regioselectivity decarbonylation; and (3) although the coordi-
nation group complicates the overall synthesis, it could be easily removed. To validate our hypothesis, we started our investigations with N-pyrimidinyl 2-benzoyl indole 1a as our model substrate. After judicious optimization of all reaction parameters,10 we dicovered that the combined use of Ni(cod)2, IMes·HCl and Cs2CO3 in dioxane gave 2-phenyl indole 2a in 92% yield (Table 1, entry 1). As anticipated, the efficiency was found to be strongly dependent on the nature of the ligand (entries 2−6). Among all of ligands examined, N-heterocyclic carbenes (NHCs) were found to be critical to facilitate the targeted transformation; and IMes·HCl gave the best results. It was 587
DOI: 10.1021/jacs.7b11591 J. Am. Chem. Soc. 2018, 140, 586−589
Communication
Journal of the American Chemical Society
Figure 1. Comparison of the energy profiles (ΔG in kcal mol−1) of path A (black) and path B (blue) for the decarbonylation of indole 1a.
However, product 5i was obtained in only 49% yield when 3methylindole derivative 4i was used. Interestingly, when diketone 4j (CO at C7 and C2) was tested, only the carbonyl group at C2 was extruded and product 5j was isolated in 49% yield, thus displaying complete regioselectivity. Moreover, the pyrrole nucleus also worked: the decarbonylation took place without any difficulty to directly make the pyrrole-benzene linkage in 85% yield (5k). Furthermore, several simple diaryl ketones bearing a 2-pyridyl directing group were also subjected to this nickel-catalyzed decarbonylation conditions and reacted as expected to form the corresponding products in moderate yields (7a−7f). The proposed reaction pathway is shown in Scheme 3. The decarbonylation is initiated by the coordination between the Ni(0) complex and substrate 1 through the directing group, giving intermediate INT1 (step 1).11 The second step is the oxidative cleavage of either the C(indole)C(O) bond or the C(O)C(aryl) bond to form the corresponding aroyl nickel(II) intermediates INT2-A or INT2-B,12 which is similar to that proposed for the decarbonylation by rhodium complex.5,6 Subsequent decarbonylation generates the corresponding diaryl nickel complex INT3. Finally, reductive elimination from INT3 will afford biaryl product 2, with the regeneration of the Ni(0) catalyst. In order to further probe the mechanism of this transformation, DFT calculations were performed, and two possible mechanistic pathways are shown in Figure 1. The catalytic cycle starts from ligand exchange reaction between INT6 and substrate 1a, giving catalyst−substrate complex INT1. INT1 undergoes oxidative addition into bond a (pathway A) via TS1A, requiring an activation free energy of 12.7 kcal mol−1. This step is endergonic by 5.5 kcal mol−1 and generates INT2-A. Then CO ligand is dissociated to produce INT3. Decarbonylation via TS2 subsequently transforms INT3 to INT4, requiring an activation free energy of 27.7 kcal mol−1. The decarbonylation step is exergonic by 9.0 kcal mol −1 . Subsequently, ligand reorganization converts INT4 to INT5, which undergoes reductive elimination to give INT6 (via TS3). An alternative pathway is nickel insertion (from INT1) into bond b (INT2-B, between the carbonyl and aryl groups (pathway b)), which is disfavored by more than 20 kcal mol−1 compared to the insertion into bond a. The computed activation energy barrier for this step is 34.0 kcal mol−1,
Scheme 4. Removal of the Directing Group on Indoles
confirmed that the solvent also played a crucial role in the C C bond cleaving reaction (entries 7−9). The replacement of dioxane by other solvents under otherwise identical reaction conditions gave 2a in lower yields. Furthermore, control experiments revealed that all three catalyst components were required for the formation of 2a in high yield (entries 10−12). Having optimized the reaction conditions, the influence of the coordinating group was then explored (Scheme 2). No reaction was observed with substrates lacking a coordinating group (3a and 3b). Weakly coordinating groups such as carboxamide (3c) and urea (3d) did not deliver the corresponding products, either. The pyridine substituted indole 3e provided the decarbonylation product in 65% yield. The results suggest that a strong coordinating group is crucial for this transformation, which is consistent with our previous hypothesis. Next, we proceeded to explore the scope of this transformation by modulating the substituents on the aromatic ring (Table 2). Substrates bearing either electron-deficient or electron-rich substituent at the para-position of the aryl ring afforded good to high yields (2b−2j). A broad range of functional groups, including methyl ether (2g), trifluoromethyl (2i), ester (2j) and unprotected phenolic hydroxyl (2h), were well tolerated. Steric hindrance did not significantly affect the efficiency of the reaction, with para- (2b), ortho- (2l), meta(2k) and 3, 5-dimethyl (2m) groups giving the similar yields. Polyaromatic ketones 1n and 1o reacted smoothly to give the decarbonylation products. Electron-rich heteroaromatic groups were also tolerated, and products 2p and 2q were isolated in 85% and 82% yields, respectively. However, under the standard conditions, there were no products detected when alkyl aryl ketones were used (1r and 1s). The functional group tolerance of the indole unit was also examined (Table 3), and a wide range of functional groups such as methoxy (5b), ester (5c), fluoride (5d and 5g), nitrile (5h) and ketone (5j) moieties were compatible with the reaction. 588
DOI: 10.1021/jacs.7b11591 J. Am. Chem. Soc. 2018, 140, 586−589
Communication
Journal of the American Chemical Society
(3) Reviews/highlights on CC bond activation: (a) Crabtree, R. H. Chem. Rev. 1985, 85, 245. (b) Murakami, M.; Ito, Y. Top. Organomet. Chem. 1999, 3, 97. (c) Rybtchinski, B.; Milstein, D. Angew. Chem., Int. Ed. 1999, 38, 870. (d) Baciocchi, E.; Bietti, M.; Lanzalunga, O. Acc. Chem. Res. 2000, 33, 243. (e) Jun, C.-H. Chem. Soc. Rev. 2004, 33, 610. (f) Tu, W.; Floreancig, P. E. Org. Lett. 2007, 9, 2389. (g) Park, Y. J.; Park, J.-W.; Jun, C.-H. Acc. Chem. Res. 2008, 41, 222. (h) Murakami, M.; Matsuda, T. Chem. Commun. 2011, 47, 1100. (i) Ruhland, K. Eur. J. Org. Chem. 2012, 2012, 2683. (j) Chen, F.; Wang, T.; Jiao, N. Chem. Rev. 2014, 114, 8613. (k) Dermenci, A.; Coe, J. W.; Dong, G. Org. Chem. Front. 2014, 1, 567. (l) Liu, H.; Feng, M.; Jiang, X. Chem. Asian J. 2014, 9, 3360. (m) Souillart, L.; Cramer, N. Chem. Rev. 2015, 115, 9410. (n) Kondo, T. Eur. J. Org. Chem. 2016, 2016, 1232. (o) Murakami, M.; Ishida, N. J. Am. Chem. Soc. 2016, 138, 13759. (p) Somerville, R. J.; Martin, R. Angew. Chem., Int. Ed. 2017, 56, 6708. (4) Books on CC bond activation: (a) Grate, J. W.; Frye, G. C. In Sensors Update, Vol. 2; Baltes, H., Gçpel, W., Hesse, J., Eds.; WileyVCH: Weinheim, 1996. (b) C−C bond activation; Dong, G., Ed.; Springer Verlag: Berlin/Heidelberg, 2014. (c) Cleavage of Carbon− Carbon Single Bonds by Transition Metals; Murakami, M.; Chatani, N., Eds.; John Wiley & Sons Ltd.: Chichester, U. K., 2016. (5) Daugulis, O.; Brookhart, M. Organometallics 2004, 23, 527. (6) Lei, Z.-Q.; Li, H.; Li, Y.; Zhang, X.-S.; Chen, K.; Wang, X.; Sun, J.; Shi, Z.-J. Angew. Chem., Int. Ed. 2012, 51, 2690. (7) (a) Zeng, R.; Dong, G. J. Am. Chem. Soc. 2015, 137, 1408. (b) Dennis, J. M.; Compagner, C. T.; Dorn, S. K.; Johnson, J. B. Org. Lett. 2016, 18, 3334. (c) Xia, Y.; Lu, G.; Liu, P.; Dong, G. Nature 2016, 539, 546. (d) Xia, Y.; Wang, J.; Dong, G. Angew. Chem., Int. Ed. 2017, 56, 2376. (8) Selected reviews (a) Li, B.-J.; Yu, D.-G.; Sun, C.-L.; Shi, Z.-J. Chem. - Eur. J. 2011, 17, 1728. (b) Rosen, B. M.; Quasdorf, K. W.; Wilson, D. A.; Zhang, N.; Resmerita, A.-M.; Garg, N. K.; Percec, V. Chem. Rev. 2011, 111, 1346. (c) Yu, D.-G.; Li, B.-J.; Shi, Z.-J. Acc. Chem. Res. 2010, 43, 1486. (d) Mesganaw, T.; Garg, N. K. Org. Process Res. Dev. 2013, 17, 29. (e) Tasker, S. Z.; Standley, E. A.; Jamison, T. F. Nature 2014, 509, 299. (f) Ouyang, K.; Hao, W.; Zhang, W.-X.; Xi, Z. Chem. Rev. 2015, 115, 12045. (g) Tollefson, E. J.; Hanna, L. E.; Jarvo, E. R. Acc. Chem. Res. 2015, 48, 2344. (h) Tobisu, M.; Chatani, N. Acc. Chem. Res. 2015, 48, 1717. (I) Iwasaki, T.; Kambe, N. Top Curr. Chem. 2016, 374, 66. (9) Morioka, T.; Nishizawa, A.; Furukawa, T.; Tobisu, M.; Chatani, N. J. Am. Chem. Soc. 2017, 139, 1416. (10) See the Supporting Information for details. (11) (a) Chatani, N.; Ie, Y.; Kakiuchi, F.; Murai, S. J. Am. Chem. Soc. 1999, 121, 8645. (b) Obenhuber, A.; Ruhland, K.; Hoffmann, S. D. Organometallics 2008, 27, 3482. (12) Nickel-catalyzed reactions of strained ketones involving the oxidative addition into CC bond: (a) Murakami, M.; Ashida, S.; Matsuda, T. J. Am. Chem. Soc. 2005, 127, 6932. (b) Murakami, M.; Ashida, S.; Matsuda, T. Tetrahedron 2006, 62, 7540. (c) Murakami, M.; Ishida, N.; Miura, T. Chem. Commun. 2006, 643. (d) Auvinet, A.-L.; Harrity, J. P. A. Angew. Chem., Int. Ed. 2011, 50, 2769. (e) Liu, L.; Ishida, N.; Murakami, M. Angew. Chem., Int. Ed. 2012, 51, 2485. (f) Kumar, P.; Louie, J. Org. Lett. 2012, 14, 2026. (g) Kumar, P.; Zhang, K.; Louie, J. Angew. Chem., Int. Ed. 2012, 51, 8602. (h) Thakur, A.; Facer, M. E.; Louie, J. Angew. Chem., Int. Ed. 2013, 52, 12161. (i) Juliá-Hernández, F.; Ziadi, A.; Nishimura, A.; Martin, R. Angew. Chem., Int. Ed. 2015, 54, 9537. (13) Ackermann, L.; Lygin, A. V. Org. Lett. 2011, 13, 3332.
which is higher than the total activation energy in pathway a. Consequently, pathway b could be ruled out at this stage. Finally, we attempted to remove the directing group from the decarbonylation products (Scheme 4). Upon treatment of 2a and 2f with NaOEt in dimethyl sulfoxide (DMSO) at 100 °C,13 the corresponding NH indoles 8a and 8f were obtained in 68 and 67% yields, respectively. In summary, we have described a nickel-catalyzed decarbonylation process that proceeds via the cleavage of two CC bonds. This method not only offers an alternative way to synthesize 2-substituted indoles but also sets the basis for designing fundamentally new reactivity within Ni catalysis. Preliminary studies appear to support preferential oxidative addition into the CC bond between the carbonyl group and indole as the key step. The application of this strategy to other CC bonds as well as computational studies aimed at revealing the mechanism of the reaction are currently being investigated in our laboratory.
■
ASSOCIATED CONTENT
* Supporting Information S
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/jacs.7b11591. Experimental details and spectral data (PDF)
■
AUTHOR INFORMATION
Corresponding Authors
*
[email protected] *
[email protected] ORCID
Peng-Fei Xu: 0000-0002-5746-758X Hao Wei: 0000-0002-7951-683X Author Contributions §
These authors contributed equally to this work.
Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS We are grateful to the financial support from the National Natural Science Foundation of China (NSFC 21502149 and 21632003) and Scientific Research Program Funded by Shaanxi Provincial Education Department (Program No. 17JS129 and 15JK1749). We thank Prof. Zhi-Xiang Yu and Dr. Uwe Schneider for insightful discussions.
■
REFERENCES
(1) (a) Murphy, A. R.; Fréchet, J. M. J. Chem. Rev. 2007, 107, 1066. (b) Hughes, R. A.; Moody, C. J. Angew. Chem., Int. Ed. 2007, 46, 7930. (c) Dolle, R. E.; Bourdonnec, B. L.; Worm, K.; Morales, G. A.; Thomas, C. J.; Zhang, W. J. Comb. Chem. 2010, 12, 765. (d) Young, I. S.; Thornton, P. D.; Thompson, A. Nat. Prod. Rep. 2010, 27, 1801. (e) Wang, C.; Dong, H.; Hu, W.; Liu, Y.; Zhu, D. Chem. Rev. 2012, 112, 2208. (2) (a) Murakami, M.; Amii, H.; Ito, Y. Nature 1994, 370, 540. (b) Murakami, M.; Amii, H.; Shigeto, K.; Ito, Y. J. Am. Chem. Soc. 1996, 118, 8285. (c) Murakami, M.; Itahashi, T.; Amii, H.; Takahashi, K.; Ito, Y. J. Am. Chem. Soc. 1998, 120, 9949. (d) Masuda, Y.; Hasegawa, M.; Yamashita, M.; Nozaki, K.; Ishida, N.; Murakami, M. J. Am. Chem. Soc. 2013, 135, 7142. (e) Kaneda, K.; Azuma, H.; Wayaku, M.; Tehanishi, S. Chem. Lett. 1974, 3, 215. (f) Dermenci, A.; Whittaker, R.; Dong, G. Org. Lett. 2013, 15, 2242. (g) Whittaker, R.; Dong, G. Org. Lett. 2015, 17, 5504. (h) Dermenci, A.; Whittaker, R. E.; Gao, Y.; Cruz, F. A.; Yu, Z.-X.; Dong, G. Chem. Sci. 2015, 6, 3201. 589
DOI: 10.1021/jacs.7b11591 J. Am. Chem. Soc. 2018, 140, 586−589
