Transition-metal-free three-component acetalation-pyridylation of alkenes via photoredox catalysis

doi:10.1016/S1872-2067(21)63917-7

Abstract

Abstract:

A general transition-metal-free photoinduced acetalation-pyridylation of alkenes using diethoxyacetic acid and cyanopyridine was developed under mild conditions. By employing 4CzIPN as the photocatalyst and Cs₂CO₃ as the base, a diverse range of styrene derivatives and cyanopyridines worked well to give the desired products. The versatility of this method is highlighted by its application in the construction of various functional groups and the late-stage modification of drugs. Importantly, some of the synthesized compounds showed good in vitro antitumor activity, indicating that this protocol is of significance and potential for antitumor drug development.

Key words: Visible-light promoted, Aldehyde, Diverse transformation, Late-stage modification, Antitumor

Chun-Hua Ma, Yu Ji, Jie Zhao, Xing He, Shu-Ting Zhang, Yu-Qin Jiang, Bing Yu. Transition-metal-free three-component acetalation-pyridylation of alkenes via photoredox catalysis[J]. Chinese Journal of Catalysis, 2022, 43(3): 571-583.

×
share this article

Add to citation manager EndNote|Ris|BibTeX

URL: https://www.cjcatal.com/EN/10.1016/S1872-2067(21)63917-7

https://www.cjcatal.com/EN/Y2022/V43/I3/571

Figures/Tables 13

Scheme 1. Transition metal-free photocatalytic cascade acetalation/pyridylation reaction of alkenes.

Table 1 Optimization of reaction conditions a.

Entry	Catalyst (3 mol%)	Base (2 equiv.)	Solvent	Yield ^b (%)
1	4CzIPN	Cs₂CO₃	DMF	50
2	4CzIPN	Cs₂CO₃	DMAC	56
3	4CzIPN	Cs₂CO₃	NMP	53
4	4CzIPN	Cs₂CO₃	DMSO	86
5	4CzIPN	Na₂CO₃	DMSO	50
6	4CzIPN	K₂CO₃	DMSO	40
7	4CzIPN	Et₃N	DMSO	20
8	4CzIPN	DIPEA	DMSO	27
9	4CzIPN	DMAP	DMSO	17
10	4CzIPN	—	DMSO	N.R.
11 ^c	4CzIPN	Cs₂CO₃	DMSO	N.R.
12	—	Cs₂CO₃	DMSO	N.R.

Scheme 2. Scope of cyanopyridine. Reaction conditions: 1 (0.2 mmol), 2a (2.5 equiv.), 3a (2.5 equiv.), 4CzIPN (3 mol%), Cs2CO3 (2 equiv.), DMSO (2 mL), r.t., blue LED, 24 h under N2 atmosphere. Isolated yields were given. a Irradiation at 390 nm.

Scheme 3. Scope of styrene and glyoxylic acid acetal. Reaction conditions: 1a (0.2 mmol), 2 (2.5 equiv.), 3 (2.5 equiv.), 4CzIPN (3 mol%), Cs2CO3 (2 equiv.), DMSO (2 mL), r.t., blue LED, 24 h under N2 atmosphere. Isolated yields were given.

Scheme 4. Late-stage modification of natural resources and drug molecules. Reaction conditions: 1a (0.2 mmol), 2 (2.5 equiv.), 3a (2.5 equiv.), 4CzIPN (3 mol%), Cs2CO3 (2 equiv.), DMSO (2 mL), r.t., blue LED, 24 h under N2 atmosphere. Isolated yields were given.

Scheme 5. Hydrolysis of acetal products 4 or 5. Reaction conditions: 4 or 5 (0.1 mmol), 2 mol/L HCl (2 mL), r.t., 3 h. Isolated yields were given.

Scheme 6. The formylation-pyridylation reaction in one pot. Reaction conditions: 1a (0.2 mmol), 2 (2.5 equiv.), 3 (2.5 equiv.), 4CzIPN (3 mol%), Cs2CO3 (2 equiv.), DMSO (2 mL), r.t., blue LED, 24 h under N2 atmosphere; then 2 mol/L HCl (2 mL), r.t., 3 h. Isolated yields were given.

Scheme 7. Further functional group transformation. (i) 6a (0.2 mmol), NaBH4 (1.5 equiv.), MeOH (2 mL), r.t., 3 h. (ii) 6a (0.2 mmol), NaClO2 (5 equiv.), NaH2PO4 (10 equiv.), tert-butanol (2 mL), H2O (1 mL), r.t., 6 h. (iii) PPh3CH3Br (3 equiv.), t-BuOK (2 equiv.), THF (5 mL), r.t., 0.5 h; then 6a (0.2 mmol), r.t., 12 h. (iv) 6a (0.2 mmol), CH3MgBr (1 equiv.), THF (1 mL), r.t., 1 h. Isolated yields were given.

Fig. 1. The color-coded radar diagrams based on sensitivity experiments.

Fig. 2. Fluorescence quenching experiments.

Scheme 8. Control experiment.

Scheme 9. The proposed mechanism.

Scheme 10. The in vitro antitumor activity of 4o, 4ac, 6c, and 6u against Ramos cells, Rec-1 cells, and HeLa cells.

References

[1]	T. S. Harrison, L. J. Scott, Drugs, 2005, 65, 2309-2336.
[2]	E. Vitaku, D. T. Smith, J. T. Njardarson, J. Med. Chem., 2014, 57, 10257-10274.
[3]	A.-Y. Guan, C.-L. Liu, X.-F. Sun, Y. Xie, M.-A. Wang, Biorg. Med. Chem., 2016, 24, 342-353.
[4]	M. N. Zafar, A. H. Atif, M. F. Nazar, S. H. Sumrra, E. S. Gul, R. Paracha, Russ. J. Coord. Chem., 2016, 42, 1-18.
[5]	P. Bhutani, G. Joshi, N. Raja, N. Bachhav, P. K. Rajanna, H. Bhutani, A. T. Paul, R. Kumar, J. Med. Chem., 2021, 64, 2339-2381.
[6]	C. Jin, K. Xu, X. Fan, C. Liu, J. Tan, Chin. Chem. Lett., 2020, 31, 91-94.
[7]	Q.-Q. Zhao, J. Chen, X.-S. Zhou, X.-Y. Yu, J.-R. Chen, W.-J. Xiao, Chem. Eur. J., 2019, 25, 8024-8029.
[8]	X.-L. Yu, J.-R. Chen, D.-Z. Chen, W.-J. Xiao, Chem. Commun., 2016, 52, 8275-8278.
[9]	Z. Wu, M. Hu, J. Li, W. Wu, H. Jiang, Org. Biomol. Chem., 2021, 19, 3036-3054.
[10]	S. Zhang, C. Wang, X. Ye, X. Shi, Angew. Chem. Int. Ed., 2020, 59, 20470-20474.
[11]	J. Zhang, J.-Y. Wang, M.-H. Huang, W.-J. Hao, X.-C. Tu, S.-J. Tu, B. Jiang, J. Org. Chem., 2020, 85, 7036-7044.
[12]	X.-Y. Yu, Q.-Q. Zhao, J. Chen, W.-J. Xiao, J.-R. Chen, Acc. Chem. Res., 2020, 53, 1066-1083.
[13]	Y. Yin, Y. Li, T. P. Gonçalves, Q. Zhan, G. Wang, X. Zhao, B. Qiao, K.-W. Huang, Z. Jiang, J. Am. Chem. Soc., 2020, 142, 19451-19456.
[14]	Y.-C. Wu, Y.-T. Xiao, Y.-Z. Yang, R.-J. Song, J.-H. Li, ChemCatChem, 2020, 12, 5312-5329.
[15]	X. Qi, T. Diao, ACS Catal., 2020, 10, 8542-8556.
[16]	X. Bao, J. Li, W. Jiang, C. Huo, Synthesis, 2019, 51, 4507-4530.
[17]	T. Koike, M. Akita, Chem, 2018, 4, 409-437.
[18]	X. Ren, Z. Lu, Chin. J. Catal., 2019, 40, 1003-1019.
[19]	M. Zhou, P. Qin, L. Jing, J. Sun, H. Du, Chin. J. Org. Chem., 2020, 40, 598-613.
[20]	Q. Fu, Z.-Y. Bo, J.-H. Ye, T. Ju, H. Huang, L.-L. Liao, D.-G. Yu, Nat. Commun., 2019, 10, 3592.
[21]	D. Chen, L. Xu, T. Long, S. Zhu, J. Yang, L. Chu, Chem. Sci., 2018, 9, 9012-9017.
[22]	J. Chen, S. Zhu, J. Qin, L. Chu, Chem. Commun., 2019, 55, 2336-2339.
[23]	J. Cao, G. Wang, L. Gao, H. Chen, X. Liu, X. Cheng, S. Li, Chem. Sci., 2019, 10, 2767-2772.
[24]	B. Lipp, L. M. Kammer, M. Kücükdisli, A. Luque, J. Kühlborn, S. Pusch, G. Matulevičiūtė, D. Schollmeyer, A. Sackus, T. Opatz, Chem. Eur. J., 2019, 25, 8965-8969.
[25]	F. Wang, J. Qin, S. Zhu, L. Chu, RSC Adv., 2021, 11, 142-146.
[26]	J. Shen, Y. Zhang, Y. Yu, M. Wang, Org. Chem. Front., 2021, 8, 901-907.
[27]	Y. Xia, J. Wang, J. Am. Chem. Soc., 2020, 142, 10592-10605.
[28]	T. Irrgang, R. Kempe, Chem. Rev., 2020, 120, 9583-9674.
[29]	H. Ohmiya, ACS Catal., 2020, 10, 6862-6869.
[30]	M. Vetrichelvan, S. Rakshit, S. Chandrasekaran, K. Chinnakalai, C. P. Darne, D. Doddalingappa, I. Gopikumar, A. Gupta, A. K. Gupta, A. Karmakar, T. Lakshminarasimhan, D. K. Leahy, S. Palani, V. Radhakrishnan, R. Rampulla, A. Savarimuthu, V. Subramanian, U. Velaparthi, J. Warrier, M. D. Eastgate, R. M. Borzilleri, A. Mathur, R. Vaidyanathan, Org. Process Res. Dev., 2020, 24, 1310-1320.
[31]	G. Yang, Y. Liu, K. Li, W. Liu, B. Yu, C. Hu, Chin. Chem. Lett., 2020, 31, 3233-3236.
[32]	H. Zhuang, H. Li, S. Zhang, Y. Yin, F. Han, C. Sun, C. Miao, Chin. Chem. Lett., 2020, 31, 39-48.
[33]	S. He, X. Chen, F. Zeng, P. Lu, Y. Peng, L. Qu, B. Yu, Chin. Chem. Lett., 2020, 31, 1863-1867.
[34]	G. Akcay, M. A. Belmonte, B. Aquila, C. Chuaqui, A. W. Hird, M. L. Lamb, P. B. Rawlins, N. Su, S. Tentarelli, N. P. Grimster, Q. Su, Nat. Chem. Biol., 2016, 12, 931-936.
[35]	N. London, R. M. Miller, S. Krishnan, K. Uchida, J. J. Irwin, O. Eidam, L. Gibold, P. Cimermancic, R. Bonnet, B. K. Shoichet, J. Taunton, Nat. Chem. Biol., 2014, 10, 1066-1072.
[36]	H. Huang, C. Yu, Y. Zhang, Y. Zhang, P. S. Mariano, W. Wang, J. Am. Chem. Soc., 2017, 139, 9799-9802.
[37]	S. Zhang, Z. Tan, H. Zhang, J. Liu, W. Xu, K. Xu, Chem. Commun., 2017, 53, 11642-11645.
[38]	N. Meng, Y. Lv, Q. Liu, R. Liu, X. Zhao, W. Wei, Chin. Chem. Lett., 2021, 32, 258-262.
[39]	Q.-W. Gui, F. Teng, Z.-C. Li, Z.-Y. Xiong, X.-F. Jin, Y.-W. Lin, Z. Cao, W.-M. He, Chin. Chem. Lett., 2021, 32, 1907-1910.
[40]	Z. Gan, G. Li, X. Yang, Q. Yan, G. Xu, G. Li, Y.-Y. Jiang, D. Yang, Sci. China Chem. 2020, 63, 1652-1658.
[41]	B.-G. Cai, J. Xuan, W.-J. Xiao, Sci. Bull., 2019, 64, 337-350.
[42]	C. Ye, B.-G. Cai, J. Lu, X. Cheng, L. Li, Z.-W. Pan, J. Xuan, J. Org. Chem., 2021, 86, 1012-1022.
[43]	Y. Chen, L.-Q. Lu, D.-G. Yu, C.-J. Zhu, W.-J. Xiao, Sci. China Chem., 2019, 62, 24-57.
[44]	J. Qi, F.-L. Zhang, J.-K. Jin, Q. Zhao, B. Li, L.-X. Liu, Y.-F. Wang, Angew. Chem. Int. Ed., 2020, 59, 12876-12884.
[45]	Y. Gao, Y. Liu, J.-P. Wan, J. Org. Chem., 2019, 84, 2243-2251.
[46]	I. B. Krylov, E. R. Lopateva, I. R. Subbotina, G. I. Nikishin, B. Yu, A. O. Terent'ev, Chin. J. Catal., 2021, 42, 1700-1711.
[47]	D.-Q. Dong, L.-X. Li, G.-H. Li, Q. Deng, Z.-L. Wang, S. Long, Chin. J. Catal., 2019, 40, 1494-1498.
[48]	K. Sun, F. Xiao, B. Yu, W.-M. He, Chin. J. Catal., 2021, 42, 1921-1943.
[49]	J. Chen, Y. Li, L. Mei, H. Wu, Chin. J. Org. Chem., 2019, 39, 3040-3050.
[50]	M. Miao, L.-L. Liao, G.-M. Cao, W.-J. Zhou, D.-G. Yu, Sci. China Chem., 2019, 62, 1519-1524.
[51]	J. Xuan, Z.-G. Zhang, W.-J. Xiao, Angew. Chem. Int. Ed., 2015, 54, 15632-15641.
[52]	L. McMurray, T. M. McGuire, R. L. Howells, Synthesis, 2020, 52, 1719-1737.
[53]	J. Schwarz, B. König, Green Chem., 2018, 20, 323-361.
[54]	L. Ren, M. Ran, J. He, Y. Qian, Q. Yao, Chin. J. Org. Chem., 2019, 39, 1583-1595.
[55]	C. Ma, Z. Feng, J. Li, D. Zhang, W. Li, Y. Jiang, B. Yu, Org. Chem. Front., 2021, 8, 3286-3291.
[56]	Y.-Q. Jiang, J. Li, Z.-W. Feng, G.-Q. Xu, X. Shi, Q.-J. Ding, W. Li, C.-H. Ma, B. Yu, Adv. Synth. Catal., 2020, 362, 2609-2614.
[57]	F.-L. Zeng, H.-L. Zhu, X.-L. Chen, L.-B. Qu, B. Yu, Green Chem., 2021, 23, 3677-3682.
[58]	K. Sun, Q.-Y. Lv, X. Chen, L. Qu, B. Yu, Green Chem., 2021, 23, 232-248.
[59]	X. Yuan, G. Yang, B. Yu, Chin. J. Org. Chem., 2020, 40, 3620-3632.
[60]	L. Pitzer, F. Schäfers, F. Glorius, Angew. Chem. Int. Ed., 2019, 58, 8572-8576.
[61]	F. Gao, K. Sun, X.-L. Chen, T. Shi, X.-Y. Li, L.-B. Qu, Y.-F. Zhao, B. Yu, J. Org. Chem., 2020, 85, 14744-14752.
[62]	S. Zhu, J. Qin, F. Wang, H. Li, L. Chu, Nat. Commun., 2019, 10, 749.
[63]	H. Huang, X. Li, C. Yu, Y. Zhang, P. S. Mariano, W. Wang, Angew. Chem. Int. Ed., 2017, 56, 1500-1505.
[64]	W. Xu, J. Ma, X.-A. Yuan, J. Dai, J. Xie, C. Zhu, Angew. Chem. Int. Ed., 2018, 57, 10357-10361.
[65]	T. Ju, Q. Fu, J.-H. Ye, Z. Zhang, L.-L. Liao, S.-S. Yan, X.-Y. Tian, S.-P. Luo, J. Li, D.-G. Yu, Angew. Chem. Int. Ed., 2018, 57, 13897-13901.
[66]	W.-J. Zhou, Z.-H. Wang, L.-L. Liao, Y.-X. Jiang, K.-G. Cao, T. Ju, Y. Li, G.-M. Cao, D.-G. Yu, Nat. Commun., 2020, 11, 3263.
[67]	M. A. Bryden, E. Zysman-Colman, Chem. Soc. Rev., 2021, 50, 7587-7680.
[68]	D. Leifert, A. Studer, Angew. Chem. Int. Ed., 2020, 59, 74-108.
[69]	T.-Y. Shang, L.-H. Lu, Z. Cao, Y. Liu, W.-M. He, B. Yu, Chem. Commun., 2019, 55, 5408-5419.
[70]	H.-L. Zhu, F.-L. Zeng, X.-L. Chen, K. Sun, H.-C. Li, X.-Y. Yuan, L.-B. Qu, B. Yu, Org. Lett., 2021, 23, 2976-2980.