基于氘代二甲基亚砜(DMSO-d6)实现吲哚C(2)位选择性甲硫基化与三氘甲硫基化反应

doi:10.6023/cjoc202310026

有机化学 ›› 2024, Vol. 44 ›› Issue (5): 1576-1583.DOI: 10.6023/cjoc202310026 上一篇下一篇

研究论文

基于氘代二甲基亚砜(DMSO-d₆)实现吲哚C(2)位选择性甲硫基化与三氘甲硫基化反应

张娟^a, 王奕森^a, 田钰^a, 徐晶^a, 高文超^a, 常宏宏^a^,^b^,^*(), 孟凡会^c^,^*(), 杨朋^d^,^*()

a 太原理工大学生物医学工程学院太原 030024
b 山西天宏达安医药科技有限公司山西晋中 030600
c 太原理工大学省部共建煤基能源清洁高效利用国家重点实验室太原 030024
b 山东师范大学化学化工与材料科学学院济南 250014

收稿日期:2023-10-26 修回日期:2023-12-24 发布日期:2024-01-18
基金资助:
太原理工大学省部共建煤基能源清洁高效利用国家重点实验室开放基金(SKL202102); 山西省自然科学基金(20210302124123); 山西省自然科学基金(202303021211033)

Regioselective C(2) Methylthiolation and d₃-Methylthiolation of Indoles Based on Dimethyl Sulfoxide (DMSO-d₆) Reagents

Juan Zhang^a, Yisen Wang^a, Yu Tian^a, Jing Xu^a, Wenchao Gao^a, Honghong Chang^a^,^b(), Fanhui Meng^c(), Peng Yang^d()

a College of Biomedical Engineering, Taiyuan University of Technology, Taiyuan 030024
b Shanxi Tihondan Pharmaceutical Technology Co. Ltd., Jinzhong, Shanxi 030600
c State Key Laboratory of Clean and Efficient Coal Utilization, Taiyuan University of Technology, Taiyuan 030024
b College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan 250014

Received:2023-10-26 Revised:2023-12-24 Published:2024-01-18
Contact: *E-mail: changhonghong@tyut.edu.cn; mengfanhui@tyut.edu.cn; yangpeng@sdnu.edu.cn
Supported by:
State Key Laboratory of Clean and Efficient Coal Utilization, Taiyuan University of Technology(SKL202102); Natural Science Foundation of Shanxi Province(20210302124123); Natural Science Foundation of Shanxi Province(202303021211033)

文章分享

1. 241576S.pdf(1940KB)

摘要/Abstract

发展了一种Cu(OAc)₂介导吲哚衍生物的C(2)选择性甲硫基化与三氘甲硫基化反应. 该转化以二甲基亚砜(DMSO)作为甲硫基来源与溶剂, 以中等至良好收率得到C(2)-甲硫基取代吲哚, 当选用DMSO-d₆作为反应试剂时, 也可合成得到C(2)-三氘甲硫基取代吲哚. 同时, 该反应不依赖于高温条件, 转化可能涉及自由基途径.

关键词: 铜, 吲哚, 三氘甲硫基化, 甲硫基化, 二甲基亚砜(DMSO)

Cu(OAc)₂ mediated C(2)-selective d₃-methylthiolation and methylthiolation of indoles were developed. With the choice of dimethyl sulfoxide (DMSO) as sulfur source and solvent, methylthiolation reaction could be achieved in moderate to good yields, and d₃-methylthiolated products could also be obtained with DMSO-d₆ as reagent just by prolong the reaction time. Moreover, this methylthiolation didn’t depend on high temperature, and radical pathway might be involved in this transformation.

Key words: copper, indole, d₃-methylthiolation, methylthiolation, dimethyl sulfoxide (DMSO)

引用此文

张娟, 王奕森, 田钰, 徐晶, 高文超, 常宏宏, 孟凡会, 杨朋. 基于氘代二甲基亚砜(DMSO-d₆)实现吲哚C(2)位选择性甲硫基化与三氘甲硫基化反应[J]. 有机化学, 2024, 44(5): 1576-1583.

Juan Zhang, Yisen Wang, Yu Tian, Jing Xu, Wenchao Gao, Honghong Chang, Fanhui Meng, Peng Yang. Regioselective C(2) Methylthiolation and d₃-Methylthiolation of Indoles Based on Dimethyl Sulfoxide (DMSO-d₆) Reagents[J]. Chinese Journal of Organic Chemistry, 2024, 44(5): 1576-1583.

导出引用 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

分享此文

图/表 7

Figure 1. Examples of small-molecule drugs containing methylthio group

Scheme 1. Strategies for C—H methylthiolation of indoles

Entry	[Cu]	Ligand	Oxidant	Yield^b/%
1	CuI	dppp	TBPB	N.D.
2	CuBr	dppp	TBPB	N.D.
3	Cu(acac)₂	dppp	TBPB	Trace
4	Cu(OTf)₂	dppp	TBPB	N.D.
5	CuTc	dppp	TBPB	36
6	CuOAc	dppp	TBPB	42
7	Cu(OAc)₂	dppp	TBPB	75 (62)^c
8	Cu(OAc)₂	BINAP	TBPB	35
9	Cu(OAc)₂	PCy₃	TBPB	43
10	Cu(OAc)₂	dtbpy	TBPB	38
11	Cu(OAc)₂	dppp	MnO₂	Trace
12	Cu(OAc)₂	dppp	DTBP	30
13	Cu(OAc)₂	dppp	TBHP	40
14		dppp	TBPB	N.D.
15	Cu(OAc)₂		TBPB	23
16	Cu(OAc)₂	dppp		Trace

Table 1. Representative results for the optimization of methylthiolation of indolesa

Table 2. Substrates scope of the copper-mediated methylthiolation of indolesa,b

Table 3. Substrate scope of the copper-mediated d3-methylthiolation of indolesa,b

Scheme 2. Control experiments

Scheme 3. Proposed mechanism

参考文献 22

[1]	(a) Jiang, X. Sulfur Chemistry, Springer, Switzerland, 2019, p. 475. pmid: 28418240
	(b) Feng, M.; Tang, B.; Liang, H. S.; Jiang, X. Curr. Top. Med. Chem. 2016, 16, 1200. pmid: 28418240
	(c) Dunbar, K. L.; Scharf, D. H.; Litomska, A.; Hertweck, C. Chem. Rev. 2017, 117, 5521. doi: 10.1021/acs.chemrev.6b00697 pmid: 28418240
	(d) Ilardi, E. A.; Vitaku, E.; Njardarson, J. T. J. Med. Chem. 2014, 57, 2832. pmid: 28418240
[2]	(a) Wang, N.; Saidhareddy, P.; Jiang, X. Nat. Prod. Rep. 2020, 37, 246.
	(b) Li, X.; Wang, X.; Li, Y.; Xiao, J.; Du, Y. Org. Biomol. Chem. 2022, 20, 4471.
[3]	(a) Shen, C.; Qiao, J.; Zhao, L.; Zheng, K.; Jin, J.; Zhang, P. Catal. Commun. 2017, 92, 114.
	(b) Li, H. L.; Kuninobu, Y.; Kanai, M. Angew. Chem., Int. Ed. 2017 129, 1517.
	(c) Chen, S.; Guo, X.; Hou, H.; Geng, S.; Liu, Z.; He, Y.; Xue, X.; Feng, Z. Angew. Chem., Int. Ed. 2023, 62, e202303470.
[4]	(a) Zhang, C.; Zhou, Y.; Huang, J.; Tu, C.; Zhou, X.; Yin, G. Org. Biomol. Chem. 2018, 16, 6316.
	(b) Hu, L.; Wang, D.; Chen, X.; Yu, L.; Yu, Y.; Tan, Z.; Zhu, G. Org. Biomol. Chem. 2017, 15, 5674.
	(c) Wang, M.; Qiao, Z.; Zhao, J.; Jiang, X. Org. Lett. 2018, 20, 6193.
	(d) Zhang, B.; Li, X.; Li, X.; Sun, F.; Du, Y. Chin. J. Chem. 2020, 39, 887.
[5]	(a) Chen, X.; Hao, X. S.; Goodhue, C. E.; Yu, J. Q. J. Am. Chem. Soc. 2006, 128, 6790.
	(b) Dai, C.; Xu, Z.; Huang, F.; Yu, Z.; Gao, Y.-F. J. Org. Chem. 2012, 77, 4414.
	(c) Chu, L.; Yue, X.; Qing, F.-L. Org. Lett. 2010, 12, 1644.
	(d) Liu, F. Org. Biomol. Chem. 2023, 21, 1153.
[6]	(a) Wu, X.-F.; Natteb, K. Adv. Synth. Catal. 2016, 358, 336.
	(b) Tashrifi, Z.; Khanaposhtani, M. M.; Larijani, B.; Mahdavi, M. Adv. Synth. Catal. 2020, 362, 65. doi: 10.1002/adsc.201901021
	(c) Lu, H.; Tong, Z.; Peng, L.; Wang, Z.; Yin, S.-F.; Kambe, N.; Qiu, R. Top Curr. Chem. 2022, 380, 55.
[7]	(a) Tian, Y.; Zhang, J. ; Gao, W.; Chang, H. Chin. J. Org. Chem. 2023, 43, 2391 (in Chinese).
	( 田钰, 张娟, 高文超, 常宏宏, 有机化学, 2023, 43, 2391.)
	(b) Sun, Q.; Soule, J.-F. Chem. Soc. Rev. 2021, 50, 10806.
[8]	For review see: Li, X.; Wang, X.; Li, Y.; Xiao, J.; Du, Y. Org. Biomol. Chem. 2022, 20, 4471.
[9]	(a) Zhang, Z.; Chen, P.; Liu, G. Chem. Soc. Rev. 2022, 51, 1640.
	(b) Li, Z.-L. Fang, G.-C.; Gu, Q.-S.; Liu, X.-Y. Chem. Soc. Rev. 2020, 49, 32.
[10]	(a) Zheng. C.; You. S.-L. Nat. Prod. Rep. 2019, 36, 1589. doi: 10.1039/c8np00098k pmid: 25255204
	(b) Leitch. J. A.; Bhonoah. Y.; Frost. C. G. ACS Catal. 2017, 7, 5618. pmid: 25255204
	(c) Vitaku, E.; Smith, D. T.; Njardarson, J. T. J. Med. Chem. 2014, 57, 10257. doi: 10.1021/jm501100b pmid: 25255204
[11]	(a) Ankade, S. B.; Shabade, A. B.; Soni, V.; Punji, B. ACS Catal. 2021, 11, 3268.
	(b) Sandtorv, A. H. Adv. Synth. Catal. 2015, 357, 2403.
	(c) Joucla, L.; Djakovitch, L. Adv. Synth. Catal. 2009, 351, 673.
	(d) Wen, J.; Shi, Z. Acc. Chem. Res. 2021, 54, 1723.
	(e) Liu, Y.-H.; Xie, P.-P.; Liu, L.; Fan, J.; Zhang, Z.-Z.; Hong, X.; Shi, B.-F. J. Am. Chem. Soc. 2021, 143, 19112.
[12]	(a) Gensch, T.; Klauck, F. J. R.; Glorius, F. Angew. Chem., Int. Ed. 2016, 55, 11287.
	(b) Zou, J.-F.; Huang, W.-S.; Li, L.; Xu, Z.; Zheng, Z.-J.; Yang, K.-F.; Xu, L.-W. RSC Adv. 2015, 5, 30389.
[13]	Wu, Y.; Ding, H.; Zhao, M.; Ni, Z.-H.; Cao, J.-P. Green Chem. 2020, 22, 4906.
[14]	Zhang, L.-Y.; Wu, Y.-H.; Wang, N.-X.; Gao, X.-W.; Yan, Z.; Xu, B.-C.; Liu, N.; Wang, B.-Z.; Xing, Y. Eur. J. Org. Chem. 2021, 2021, 1446.
[15]	Sharma, P.; Rohilla, S.; Jain, N. J. Org. Chem. 2015, 80, 4116.
[16]	Huang, J.; Sun, W.-W.; Li, J.-Q.; Ma, A.-D.; Liu, J.-K.; Wu, B. Org. Lett. 2023, 25, 528. doi: 10.1021/acs.orglett.2c04270 pmid: 36646633
[17]	(a) Barreiro, E. J.; Kümmerle, A. E.; Fraga, C. A. M. Chem. Rev. 2011, 111, 5215. doi: 10.1021/cr200060g pmid: 24151256
	(b) Schönherr, H.; Cernak, T. Angew. Chem., Int. Ed. 2013, 52, 12256. doi: 10.1002/anie.201303207 pmid: 24151256
[18]	Goyal, V.; Sarki, N.; Narani, A.; Naik, G.; Natte, K.; Jagadeesh, R. V. Coord. Chem. Rev. 2023, 474, 214827.
[19]	Schmidt, C. Nat. Biotechnol. 2017, 35, 493.
[20]	(a) Gao, Q.; Shang, Y.; Song, F.; Ye, J.; Liu, Z.-S.; Li, L.; Cheng, H.-G.; Zhou, Q. J. Am. Chem. Soc. 2019, 141, 15986.
	(b) Wang, M.; Zhao, Y.; Zhao, Y.; Shi, Z. Sci. Adv. 2020, 6, eaba0946.
[21]	(a) Cui, X.; Liu, X.; Wang, X.; Tian, W.; Wei, D.; Huang, G. ChemistrySelect 2017, 2, 8607.
	(b) Dighe, S. U.; Samanta, S. K.; Kolle, S.; Batra, S. Tetrahedron 2017, 73, 2455.
[22]	(a) Chen, Z.; Cao, G.; Zhang, F.; Li, H.; Xu, J.; Miao, M.; Ren, H. Synlett 2017, 28, 1795.
	(b) Rastogi, G. K.; Deka, B.; Deb, M. L.; Baruah, P. K. Eur. J. Org. Chem. 2020, 2020, 424. doi: 10.1002/ejoc.201901415

基于氘代二甲基亚砜(DMSO-d₆)实现吲哚C(2)位选择性甲硫基化与三氘甲硫基化反应

Regioselective C(2) Methylthiolation and d₃-Methylthiolation of Indoles Based on Dimethyl Sulfoxide (DMSO-d₆) Reagents

RichHTML

PDF

补充材料