Home Journals Articles Updates About
CN
image
收藏切换
Synthesis of planar chiral isoquinolinone-fused ferrocenes through palladium-catalyzed C-H functionalization reaction
收藏切换
PDF
Lantao Liua, c, d, *, Huihui Liub, Zhenzhen Zuod, An-An Zhanga, Zhongyi Lia, Tuanjie Menga, Wei Wub, Yuanzhao Huad, Guoliang Maob, *
Chinese Chemical Letters | 2021, 32(1) : 239 - 242
Less
收藏切换
Chinese Chemical Letters | 2021, 32(1): 239-242
• Communication •
Synthesis of planar chiral isoquinolinone-fused ferrocenes through palladium-catalyzed C-H functionalization reaction
Full
Lantao Liua, c, d, *, Huihui Liub, Zhenzhen Zuod, An-An Zhanga, Zhongyi Lia, Tuanjie Menga, Wei Wub, Yuanzhao Huad, Guoliang Maob, *
Affiliations
  • a Henan Engineering Laboratory of Green Synthesis for Pharmaceuticals, College of Chemistry and Chemical Engineering, Shangqiu Normal University, Shangqiu 476000, China
  • b College of Chemistry and Chemical Engineering, Northeast Petroleum University, Daqing 163318, China
  • c Beijing National Laboratory for Molecular Sciences (BNLMS), College of Chemistry, Peking University, Beijing 100871, China
  • d College of Chemistry, Zhengzhou University, Zhengzhou 450001, China
Published: 2021-01-15 doi: 10.1016/j.cclet.2020.10.034
Outline
收藏切换

(S, S)-Me-BI-DIME/Pd(0)-catalyzed ennantioselective C–H functionalization of N-ferrocenyl o-bromo-benzanilides has been realized, affording isoquinolinone-fused ferrocenes with up to 97% ee. The products can be transformed into planar chiral ferrocenyl monophosphines, which demonstrate their preliminary application.

(S, S)-Me-BI-DIME  /  Palladium  /  Asymmetric catalysis  /  C-H functionalization  /  Planar chiral ferrocenes
Lantao Liu, Huihui Liu, Zhenzhen Zuo, An-An Zhang, Zhongyi Li, Tuanjie Meng, Wei Wu, Yuanzhao Hua, Guoliang Mao. Synthesis of planar chiral isoquinolinone-fused ferrocenes through palladium-catalyzed C-H functionalization reaction[J]. Chinese Chemical Letters, 2021 , 32 (1) : 239 -242 . DOI: 10.1016/j.cclet.2020.10.034
Full Text
Less
Compounds containing a phenanthridinone skeleton possess remarkable biological and pharmaceutical properties, such as antilymphoma, antileukemia, antitumor, antiviral and inhibitor of HIV-1 integrase, etc. [1]. Replacement of aryl rings by ferrocenyl moieties usually improves the properties of a given biomolecule dramatically [2]. Hence, the synthesis of planar-chiral isoquinolinone-fused ferrocenes, phenanthridinone analogues, are worth expecting for biochemists and pharmaceutical chemists.
On the other hand, planar chiral ferrocenes have been extensively utilized as privileged chiral catalyst and ligands in asymmetric catalysis (Fig. 1) [3]. Therefore, intensive efforts have been devoted to their asymmetric synthesis, and significant progress has been achieved using transition-metal-catalysts [4]. Recently, asymmetric C–H bond functionalization [5] enables the concise synthesis of planar chiral ferrocenes [6-18]. The Binap/Pd catalyzed intramolecular cyclization of ferrocenyl (o-bromo)aryl ketones, independently developed by You group and Gu et al., enabled the elegant synthesis of planar chiral ferrocenes (Scheme 1a) [8a, 8b]. Then, the synthesis of planar chiral quinilinoferrocenes, with moderate enantioselectivity in some cases, was realized with (R, Sa)-O-PINAP as the ligand [8c]. Soon after that, our group reported the asymmetric synthesis of these scaffolds in excellent enantioselectivity with TADDOL-derived phosphoramidite as ligand [8d]. Stereospecific synthesis of them could also be realized via a metallocenic radical pathway [8j]. Planar-chiral lactam-fused ferrocenes, can serve as precursors of useful planar-chiral pyridines. The planar-chiral lactam-fused ferrocenes with the nitrogen atom directly linked with ferrocenyl ring, are more attractive [16, 17]. Very recently, a wonderful asymmetric oxidative annulation of twofold C–H bonds and alkynes was realized by using chiral Ni-Al bimetallic catalyst, providing such kind of planar-chiral lactam-fused ferrocenes in excellent ee values (Scheme 1b) [18]. Despite the significant achievement, the efficient asymmetric synthesis of the planar-chiral lactam-fused ferrocenes in a catalytic manner is still highly desirable. Inspired by the previous works on Pd(0)-catalyzed enantioselective C–H activation, we report herein the synthesis of planar-chiral isoquinolinone-fused ferrocenes via Pd(0)-catalyzed C–H functionalization reaction (Scheme 1c). (S, S)-Me-BI-DIME, P-chiral monophosphorus ligands developed by Tang group [19], proved to be critical, delivering the desired products with up 97% ee.
Readily available N-ferrocenyl o-bromobenzanilides 1a was selected as model substrate for the optimization of reaction conditions (Table 1). However, it is very difficult to control the enantioselectivity. The catalytic systems, used in the above mentioned reactions, are not suitable for this reaction [8]. For example, the combination of TADDOL-derived phosphoramidite L1 with Pd2(dba)3 which gave excellent enantioselectivity in the synthesis of planar chiral quinilinoferrocenes [8d], afforded 2a in just 38% yield with 57% ee (Table 1, entry 1) [20]. Although excellent yields were obtained by using L2 and L3, the ee values were even poorer (Table 1, entries 2 and 3). Both H8-BINOL-derived phosphoramidite L4 and BINOL-derived phosphoramidite L5 showed very poor enantioselectivities (Table 1, entries 4 and 5). The P-chiral birayl monophosphorus ligands developed by Tang group were then evaluated in the reaction (Table 1, entries 6-13). Ligands L6-L8 containing one P-chiral centre gave desired product in very poor ee (Table 1, entries 6-8). Pleasingly, both L9 and L10, with an additional chiral center, gave 2a in good to excellent yields (95%) and with excellent enantioselectivities (94%) (Table 1, entries 9 and 10). The addition of PivOH improved yield and enantioselectivity of the reaction (Table 1, entry 10 vs. 11). Although lower or higher temperature led to lower yields, the enantioselectivity was still excellent (Table 1, entries 12 and 13).
Under the optimized reaction conditions, the scope of N-ferrocenyl o-bromobenzanilides 1 was investigated and the result is listed in Scheme 2. The substrates, 1a-1d, with different N-protecting groups such as Et-, Bn-, nBu- and p-MeO-C6H4- groups reacted smoothly to furnish the desired products, 2a-2d, in good to excellent yields and with excellent enantioselectivity (94%–97% ee). The substrates, with substituents at the 5-position of the phenyl rings, yielded products 2e and 2f in good to excellent yields with excellent enantioselectivity (96% and 94% ee). Although substrate 1g, with a methyl group at the 4-position of the phenyl rings, led to moderate yield, the substrates with the Cl- and F- substituents on the same positions, afforded products 2h and 2i in good isolated yields with excellent enantioselectivity. Regardless of their steric effect, the substrates with the F-substituents reacted smoothly to give products 2i-2k in excellent ee value (90%-96% ee). Product 2l, with polycyclic rings, could also be obtained in good ee.
The preliminary synthetic utilization of the products were carried out, and the result was listed in Scheme 3. Treatment with 20 equiv. of PhOCH3 in TFA at 70 ℃ for 4 h, 2d was transformed to 2m, a useful synthetic building block, in 50% isolated yield with 94% ee (Scheme 3a). The absolute configuration of 2m was assigned as Sp by X-ray crystallographic analysis (CCDC: 2024984). Planar chiral phosphines have proved to be privileged ligands in transition-metal catalysed asymmetric catalysis, and for example, (R, Sp)-xyliphos shown in Fig. 1 have been successfully utilized in industrial chemistry for the manufacture of (S)-metolachlor. Therefor it is highly desirable to transform the products to useful planar chiral phosphines. To our delight, 2j and 2k worked well with Ph2PK in the presence of HMPA, generating planar ferrocene–based phosphines 3 and 4 in good yields without any erosion in enantioselectivity.
In conclusion, an efficient and highly enantioselective synthesis of planar chiral isoquinolinone-fused ferrocenes has been realized via palladium-catalyzed C–H functionalization reaction under mild condition. P-chiral biaryl monophosphorus ligand, (S, S)-Me-BI-DIME, is crucial for the enantioselectivity. Moreover, the chiral products with F-substituent could be transformed to planar ferrocene–based phosphines in one step. Further applications of the method are currently underway in our laboratory.
Declaration of competing interest
Less
The authors report no declarations of interest.
Acknowledgments
Less
We are grateful for the financial support from the National Natural Science Foundation of China (Nos. 21572126, 21202095, 14HASTIT016), Technicians Troop Construction Projects of Henan Province (No. C20150030), and Program of Science and Technology Innovation Talents of Henan Province (No. 184100510011). We would like to dedicate this work to Professor Li-Xin Dai for his 96th birthday.
References
Less
[1]
(a) D. Bellocchi, A. Macchiarulo, G. Costantino, R. Pellicciari, Bioorg. Med. Chem. 13 (2009) 1151-1157;(b) N.L. Ka, T.Y. Na, H. Na, et al., Cancer Res. 77 (2017) 2453-2463;(c) Y. Nishiyama, S. Mori, M. Makishima, et al., ACS Med. Chem. Lett. 9 (2018) 641-645.
[2]
(a) S. Top, J. Tang, A. Vessières, et al., Chem. Commun. (Camb.) (1996) 955-956;(b) Y. Wang, P. Pigeon, S. Top, M.J. McGlinchey, G. Jaouen, Angew. Chem. Int. Ed. 54 (2015) 10230-12033;(c) Y. Wang, P.M. Dansette, P. Pigeon, et al., Chem. Sci. 9 (2018) 70-78;(d) R. Wang, H. Chen, W. Yan, et al., Eur. J. Med. Chem. 190 (2020) 112109.
[3]
(a) R.G. Arrayas, J. Adrio, J.C. Carretero, Angew. Chem. Int. Ed. 45 (2006) 7674-7715;(b) H.U. Blaser, B. Pugin, F. Spindler, J. Mol. Catal. A: Chem. 231 (2005) 1-20;(c) G.C. Fu, Acc. Chem. Res. 39 (2006) 853-860;(d) G.C. Fu, Acc. Chem. Res. 37 (2004) 542-547;(e) T.J. Colacot, Chem. Rev. 103 (2003) 3101-3118;(f) L.X. Dai, T. Tu, S.L. You, W.P. Deng, X.L. Hou, Acc. Chem. Res. 36 (2003) 659-667;(g) H.U. Blaser, W. Brieden, B. Pugin, et al., Top. Catal. 19 (2002) 3-16;(h) G.C. Fu, Acc. Chem. Res. 33 (2000) 412-420;(i) A. Togni, Angew. Chem. Int. Ed. 35 (1996) 1475-1477;(j) T. Hayashi, M. Kumada, Acc. Chem. Res. 15 (1982) 395-401;(k) L.X. Dai, X.L. Hou, Chiral Ferrocenes in Asymmetric Catalysis, Wiley-VCH, Weinheim, 2010;(l) P. Stepnicka, Ferrocenes, Wiley, Chichester, 2008;(m) A. Togni, R.L. Haltermann, Metallocenes, VCH, Weinheim, 1998;(n) T. Hayashi, A. Togni, Ferrocenes, VCH, Weinheim, 1995.
[4]
D. Schaarschmidt, H. Lang, Organometallics 32 (2013) 5668-5704.
[5]
(a) R. Giri, B.F. Shi, K.M. Engle, N. Maugel, J.Q. Yu. Chem. Soc. Rev. 38 (2009) 3242-3272;(b) J. Wencel-Delord, F. Colobert, Chem. Eur. J. 19 (2013) 14010-14017;(c) K.M. Engle, J.Q. Yu, J. Org. Chem. 78 (2013) 8927-8955;(d) C. Zheng, S.L. You, RSC Adv. 4 (2014) 6173-6214;(e) B. Ye, N. Cramer, Acc. Chem. Res. 48 (2015) 1308-1318;(f) S.L. You, Asymmetric Functionalization of C-H Bonds, ; RSC, Cambridge, 2015;(g) C.G. Newton, S.G. Wang, C.C. Oliveira, N. Cramer, Chem. Rev. 117 (2017) 8908-8976;(h) T.G. Saint-Denis, R.Y. Zhu, G. Chen, Q.F. Wu, J.Q. Yu, Science 359 (2018) eaao4798;(i) J. Diesel, N. Cramer, ACS Catal. 9 (2019) 9164-9177;(k) Y. Kim, C.J. Li, Green Synth. Catal. 1 (2020) 1-11.
[6]
(a) Y. Wang, A. Zhang, L. Liu, et al., Chin. J. Org. Chem. 35 (2015) 1399-1406;(b) L.A. Lopez, E. Lopez, Dalton Trans. 44 (2015) 10128-10135;(c) D.Y. Zhu, P. Chen, J.B. Xia, ChemCatChem. 8 (2016) 68-73;(d) D.W. Gao, Q. Gu, C. Zheng, S.L. You, Acc. Chem. Res. 50 (2017) 351-356;(e) J.P. Huang, Q. Gu, S.L. You, Chin. J. Org. Chem. 38 (2018) 51-61;(f) W.L. Duan, Chin. J. Org. Chem. 39 (2019) 3598-3599;(g) C.X. Liu, Q. Gu, S.L. You, Trends Analyt. Chem. 2 (2020) 737-749.
[7]
S. Siegel, H.G. Schmalz, Angew. Chem. Int. Ed. 36 (1997) 2456-2458.
[8]
(a) R. Deng, Y. Huang, X. Ma, et al., J. Am. Chem. Soc. 136 (2014) 4472-4475;(b) D.W. Gao, Q. Yin, Q. Gu, S.L. You, J. Am. Chem. Soc. 136 (2014) 4841-4844;(c) X. Ma, Z. Gu, RSC Adv. 4 (2014) 36241-36244;(d) L. Liu, A.A. Zhang, R.J. Zhao, et al., Org. Lett. 16 (2014) 5336-5338;(e) D.W. Gao, C. Zheng, Q. Gu, S.L. You, Organometallics 34 (2015) 4618-4625;(f) D.W. Gao, Y. Gu, S.B. Wang, Q. Gu, S.L. You, Organometallics 35 (2016) 3227-3233;(g) S. Zhang, J. Lu, J. Ye, W.L. Duan, Chin. J. Org. Chem. 36 (2016) 752-759;(h) C. Nottingham, H. Müller-Bunz, P.J. Guiry, Angew. Chem. Int. Ed. 55 (2016) 11115-11119;(j) Y. Liu, J. Xu, J. Zhang, X. Xu, Z. Jin, Org. Lett. 19 (2017) 5709-5712.
[9]
(a) T. Shibata, T. Shizuno, T. Sasaki, Chem. Commun. (Camb.) 51 (2015) 7802-7804;(b) M. Murai, K. Matsumoto, Y. Takeuchi, K. Takai, Org. Lett. 17 (2015) 3102-3105;(c) Q.W. Zhang, K. An, L.C. Liu, Y. Yue, W. He, Angew. Chem. Int. Ed. 54 (2015) 6918-6921;(d) W.T. Zhao, Z.Q. Lu, H. Zheng, X.S. Xue, D. Zhao, ACS Catal. 8 (2018) 7997-8005;(e) Z.J. Cai, C.X. Liu, Q. Wang, Q. Gu, S.L. You, Nature Commun. 10 (2019) 4168.
[10]
(a) A. Urbano, G. Hernández-Torres, A.M. del Hoyo, A. Martínez-Carrión, M.C. Carreño, Chem. Commun. (Camb.) 52 (2016) 6419-6422;(b) T. Shibata, N. Uno, T. Sasaki, K.S. Kanyiva, J. Org, Chem. 81 (2016) 6266-6272.
[11]
(a) D.W. Gao, Y.C. Shi, Q. Gu, Z.L. Zhao, S.L. You, J. Am. Chem. Soc. 135 (2013) 86-89;(b) C. Pi, Y. Li, X. Cui, et al., Chem. Sci. 4 (2013) 2675-2679;(c) Y.C. Shi, R.F. Yang, D.W. Gao, S.L. You, Beilstein J. Org. Chem. 9 (2013) 1891-1896;(d) C. Pi, X. Cui, X. Liu, et al., Org. Lett. 16 (2014) 5164;(e) D.W. Gao, Q. Gu, S.L. You, J. Am. Chem. Soc. 138 (2016) 2544-2547;(f) Z.J. Cai, C.X. Liu, Q. Gu, C. Zheng, S.L. You, Angew. Chem. Int. Ed. 58 (2019) 2149-2153;(g) Y. Huang, C. Pi, X. Cui, Y. Wu, Adv. Synth. Catal. 362 (2020) 1385-1390.
[12]
J. Xu, Y. Liu, J. Zhang, X. Xu, Z. Jin, Chem. Commun. (Camb.) 54 (2018) 689-692.
[13]
(a) S. Luo, Z. Xiong, Y. Lu, Q. Zhu, Org. Lett. 20 (2018) 1837-1840;(b) M. Ito, M. Okamura, K.S. Kanyiva, T. Shibata, Organometallics 38 (2019) 4029-4035;(c) L. Jia, X. Liu, A.A. Zhang, et al., Chem. Commun. (Camb.) 56 (2020) 1737-1740.
[14]
L. Liu, H. Song, Y.H. Liu, L.S. Wu, B.F. Shi, ACS Catal. 10 (2020) 7117-7122.
[15]
(a) T. Shibata, T. Shizuno, Angew. Chem. Int. Ed. 53 (2014) 5410-5413;(b) C.X. Liu, Z.J. Cai, Q. Wang, et al., CCS Chem. 2 (2020) 642-651.
[16]
W. Xie, B. Li, S. Xu, H. Song, B. Wang, Organometallics 33 (2014) 2138-2141.
[17]
S.B. Wang, J. Zheng, S.L. You, Organometallics 35 (2016) 1420.
[18]
H. Chen, Y.X. Wang, Y.X. Luan, M. Ye, Angew. Chem. Int. Ed. 59 (2020) 9428-9432.
[19]
(a) G. Xu, C.H. Senanayake, W. Tang, Acc. Chem. Res. 52 (2019) 1101-1112;(b) H. Yang, W. Tang, Chem. Rec. 19 (2019) 1-19.
[20]
(a) T. Saget, N. Cramer, Angew. Chem. Int. Ed. 51 (2012) 12842-12845;(b) T. Saget, N. Cramer, Angew. Chem. Int. Ed. 52 (2013) 7865-7868;(c) J. Pedroni, M. Boghi, T. Saget, N. Cramer, Angew. Chem. Int. Ed. 53 (2014) 9064-9067;(d) C.G. Newton, E. Braconi, J. Kuziola, M.D. Wodrich, N. Cramer, Angew. Chem. Int. Ed. 57 (2018) 11040-11044.
Appendix
Less
Year 2021 volume 32 Issue 1
PDF
64
35
Cite this Article
BibTeX
Article Info
doi: 10.1016/j.cclet.2020.10.034
  • Receive Date：2020-09-10
  • Online Date：2026-01-04
  • Published：2021-01-15
Article Data
Affiliations
History
  • Received：2020-09-10
  • Revised：2020-10-20
  • Accepted：2020-10-21
Affiliations
    a Henan Engineering Laboratory of Green Synthesis for Pharmaceuticals, College of Chemistry and Chemical Engineering, Shangqiu Normal University, Shangqiu 476000, China
    b College of Chemistry and Chemical Engineering, Northeast Petroleum University, Daqing 163318, China
    c Beijing National Laboratory for Molecular Sciences (BNLMS), College of Chemistry, Peking University, Beijing 100871, China
    d College of Chemistry, Zhengzhou University, Zhengzhou 450001, China
References
Share
https://castjournals.cast.org.cn/joweb/ccl/EN/10.1016/j.cclet.2020.10.034
Share to
QR

Scan QR to access full text

Cite this article
BibTeX
Citations
表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
关闭全屏
  • BibTeX
  • EndNote
  • RefWorks
  • TxT
Links
Articles
Latest Articles
Most Read
Collections
Updates
Events
News
Multimedia
About
About Us
Contact
No. 86 Xueyuan South Road, Haidian District, Beijing
100081
010-62199257
qkjq@cast.org.cn

Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House