Home Journals Articles Updates About
CN
image
收藏切换
Metal-free direct C(sp3)—H functionalization of 2-alkylthiobenzoic acid to access 1, 3-benzooxathiin-4-one
收藏切换
PDF
Ke Yang*, Yi Li, Mengjie Song, Shengfei Dai, Zheng-Yi Li*, Xiaoqiang Sun
Chinese Chemical Letters | 2021, 32(1) : 146 - 149
Less
收藏切换
Chinese Chemical Letters | 2021, 32(1): 146-149
• Communication •
Metal-free direct C(sp3)—H functionalization of 2-alkylthiobenzoic acid to access 1, 3-benzooxathiin-4-one
Full
Ke Yang*, Yi Li, Mengjie Song, Shengfei Dai, Zheng-Yi Li*, Xiaoqiang Sun
Affiliations
  • Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, School of Petrochemical Engineering, Changzhou University, Changzhou 213164, China
Published: 2021-01-15 doi: 10.1016/j.cclet.2020.11.036
Outline
收藏切换

Metal-free direct α-C(sp3)—H intramolecular cyclization of 2-alkylthiobenzoic acid in the presence of Selectfluor is described. This novel strategy provides a facile and efficient method to access important 1, 3-benzooxathiin-4-one derivatives with good functional groups tolerance and yields.

Metal-free  /  C(sp3)—H functionalization  /  Selectfluor  /  1, 3-Benzooxathiin-4-one  /  Organic synthesis
Ke Yang, Yi Li, Mengjie Song, Shengfei Dai, Zheng-Yi Li, Xiaoqiang Sun. Metal-free direct C(sp3)—H functionalization of 2-alkylthiobenzoic acid to access 1, 3-benzooxathiin-4-one[J]. Chinese Chemical Letters, 2021 , 32 (1) : 146 -149 . DOI: 10.1016/j.cclet.2020.11.036
Full Text
Less
1, 3-Benzooxathiin-4-ones have received much attention due to their vital use in a large number of insecticidal and fungicidal agents, crop protection agents, and food additives (Fig. 1) [1-3]. Previous methods for the synthesis of 1, 3-benzooxathiin-4-ones mainly rely on the cross-coupling of thiophenol derivatives with alkynes [4-7] and alkenes [8, 9], or the Pummerer reaction of sulfoxide derivatives [10, 11]. However, these methods always suffer from some drawbacks, including the use of odour smelling thiophenols, the requirement of pre-functionalization of thioethers or limited substrate scope.
Recently, direct C—H bond functionalization has been regarded as one of the most effective and direct methods for the construction of C—C or C—heteroatom bond [12-24]. Within this reaction class, transition-metal mediated C(sp3)—H bond functionalization of thioether derivatives has been developed to synthesize 1, 3-benzooxathiin-4-ones. The Porcel group reported the allylic C—H bond intramolecular cyclization of 2-(allylthio)benzoic acid mediated by the excess amounts of AgOAc (Scheme 1a) [25]. Moreover, our group also demonstrated the Ag2O-promoted intramolecular C(sp3)—H bond functionalization of 2-methylthiobenzamide and sequential acidolysis to access 4H-benzo[d][1, 3]oxathiin-4-one (Scheme 1b) [26]. However, the current methods often need expensive silver salts and with the limited substrate scope. Therefore, development of a metal-free and highly efficient method via a direct C(sp3)—H functionalization for the synthesis of 1, 3-benzooxathiin-4-ones would be of great significance.
Selectfluor, as a remarkable electrophilic fluorinating reagent, has been widely used in the fluorination process in recent years due to its low toxicity, high thermal stability, good solubility and stability in polar solvents [27-30]. Besides, it can also be employed as a radical initiator, fluorine cation initiator and transition metal oxidant to achieve "fluorine-free" reactions [31-44]. In the continuing efforts for developing novel metal-free strategies in the direct C(sp3)—H functionalization, herein we disclose the Selectfluor-mediated cyclization of 2-alkylthiobenzoic acid to access 1, 3-benzooxathiin-4-one via a direct α-C(sp3)—H functionalization reaction (Scheme 1c).
Our investigation began with the direct C(sp3)—H intramolecular cyclization of 2-(ethylthio)benzoic acid 1a in the presence of Selectfluor in DCE at 80 ℃, the desired product 2a was isolated in 53% yield (Table 1, entry 1). To our delight, the subsequent examination of different reaction solvents indicated that MeCN was the optimal solvent, affording the desired product 2a in 82% isolated yield (Table 1, entries 2–7). Next, the additive agent screening showed that none of the other additives provided better results than Selectfluor (Table 1, entries 8–14). It was then noticed that the yield of 2a could not be improved any more by increasing or decreasing the amounts of Selectfluor and the reaction temperature (Table 1, entries 15–18). Finally, the desired product 2a could not be detected in the absence of Selectfluor (Table 1, entry 19).
With the optimized reaction conditions in hand, the substrate scope study on the sulfur atom substituents of 2-alkylthiobenzoic acid was carried out in Scheme 2. As expected, the substrates bearing different linear and branched alkyl substituents on the sulfur atom, including methyl, ethyl, n-propyl, n-butyl, n-hexyl, i-propyl and i-butyl, were transformed to the desired products 2a-g in good yields. Moreover, the substrates with a benzyl or phenethyl group also gave the desired products 2h-i in excellent yield. In addition, both cyano- and ester-substituted substrate were well-tolerated to afford the desired products 2j and 2k in 81% and 63% yield. It was noteworthy that the highly reactive allyl and propargyl substrates could also provide the desired products 2l-m in good yield.
Next, the substrate scope of substituents on the aromatic ring was also tested (Scheme 3). Both electron withdrawing and electron-donating groups on the phenyl ring were compatible under the current reaction system, affording the desired products 2n-u in good yields. Notably, a variety of functional groups such as methyl, methoxy and halogen groups were well-suited for this reaction, allowing for further transformations of the initial products. However, the pyridine-containing substrate 1v failed to access the desired product 2v.
To provide some insights into the reaction mechanism, a series of control experiments were carried out (Scheme 4). Firstly, radical trapping experiments were performed, and the results showed that the addition of TEMPO inhibited this process, suggesting that a single electron transfer (SET) may be involved in the reaction (Scheme 4a). Furthermore, the reaction of sulfoxide 3 with Selectfluor failed to produce the desired product 2b, indicating that the sulfoxide intermediate may not be involved in this reaction (Scheme 4b). Next, the H/D exchange could not be detected when this reaction was performed with an isotopically labelled substrate [D]-1b (Scheme 4c). The KIE experiment between 1b and [D]-1b showed that the second-order of kinetic isotope effect was observed and the cleavage of the C(sp3)—H bond may not be involved in a rate-determining step (Scheme 4d).
On the basis of previous literatures [26, 45-54] and our control experiments, a plausible mechanism has been depicted in Scheme 5. The initial oxidation of 2-methylthiobenzoic acid 1b by Selectfluor affords the radical A and radical cation B [45-48]. Then the carbon-centered radical C can be formed through a 1, 6-H radical shift process [49, 50]. Subsequently, the radical C is oxidized to the corresponding carbocation D and its isomer E in the presence of radical cation B and Selectfluor [51, 52]. Finally, an intramolecular cyclization of intermediate E and the sequential deprotonation provide the desired product 2b. However, a plausible pathway involving α-C–H fluorination and sequential intramolecular cyclization cannot be excluded at the present stage [53, 46-54].
In order to illustrate the synthetic utility of this novel method, a gram-scale reaction for the synthesis of benzooxathiin-4-one 2b was carried out (Scheme 6). When 2-(methylthio)benzoic acid 1b (1.68 g, 10 mmol) was treated with 1.5 equiv. of Selectfluor in MeCN (30 mL) at 80 ℃, the desired product 2b was obtained in 78% isolated yield.
In summary, an efficient and direct cyclization of 2-alkylthiobenzoic acid via a Selectfluor-promoted α-C(sp3)—H functionalization has been developed. This process may involve a radical pathway in the presence of Selectfluor. Moreover, this metal-free strategy also provides an important complementary method to access various 1, 3-benzooxathiin-4-one derivatives.
Declaration of competing interest
Less
The authors report no declarations of interest.
Acknowledgments
Less
We gratefully acknowledge the financial support from the National Natural Science Foundation of China (Nos. 21572026, 21702019), Advanced Catalysis and Green Manufacturing Collaborative Innovation Center, Changzhou University.
References
Less
[1]
J. Rheinheimer, U.J. Vogelbacher, E. Baumann, et al., US Patent 5569640, 1996.
[2]
M. Yamato, K. Hashigaki, Chem. Senses Flavour 4 (1979) 35-47.
[3]
A. Senning, S.O. Lawesson, Acta Chem. Scand. 16 (1962) 1175-1182.
[4]
T. Sonehara, S. Murakami, S. Yamazaki, et al., Org. Lett. 19 (2017) 4299-4302.
[5]
H.H. Wang, T. Shi, W.W. Gao, et al., Org. Biomol. Chem. 15 (2017) 8013-8017.
[6]
Y. Nishina, J. Miyata, Synthesis 44 (2012) 2607-2613.
[7]
N.G. Kundu, B. Nandi, Synlett (2001) 415-417.
[8]
X. Chaminade, L. Coulombel, S. Olivero, et al., Eur. J. Org. Chem. 2006 (2006) 3554-3593.
[9]
D.T. Mowry, W.H. Yanko, E.L. Ringwald, J. Am. Chem. Soc. 69 (1947) 2358-2361.
[10]
S. Ito, Y. Kubota, M. Asami, Chem. Lett. 45 (2016) 16-18.
[11]
M. Yamanaka, S. Shimada, W. Ando, et al., Phosphorus Sulfur Silicon Relat. Elem. 190 (2015) 1307-1308.
[12]
Q. Shao, K. Wu, Z. Zhuang, et al., Acc. Chem. Res. 53 (2020) 833-851.
[13]
X.M. Xu, D.M. Chen, Z.L. Wang, Chin. Chem. Lett. 31 (2020) 49-57.
[14]
K. Yang, M. Song, H. Liu, et al., Chem. Sci. 11 (2020) 12616-12632.
[15]
W.B. He, L.Q. Gao, X.J. Chen, et al., Chin. Chem. Lett. 31 (2020) 1895-1898.
[16]
B. Niu, K. Yang, B. Lawrence, et al., ChemSusChem 12 (2019) 2955-2969.
[17]
K. Yang, M. Song, Z. Ma, et al., Org. Chem. Front. 6 (2019) 3996-3999.
[18]
Z. Shen, C. Pi, X. Cui, et al., Chin. Chem. Lett. 30 (2019) 1374-1378.
[19]
Q. Zhao, X.S. Ji, Y.Y. Gao, et al., Org. Lett. 20 (2018) 3596-3600.
[20]
X.T. Zhu, T.S. Zhang, Q. Zhao, et al., Chem. Asian J. 13 (2018) 1157-1164.
[21]
K. Yang, D. Li, L. Zhang, et al., RSC Adv. 51 (2018) 13671-13674.
[22]
Y. Yang, J. Lan, J. You, Chem. Rev. 117 (2017) 8787-8863.
[23]
M.M. Chen, L.Y. Shao, L.J. Lun, Chin. Chem. Lett. 30 (2019) 702-706.
[24]
Z.K. Chen, B.J. Wang, J.T. Zhang, et al., Org. Chem. Front. 2 (2015) 1107-1297.
[25]
U.A. Carrillo-Arcos, J. Rojas-Ocampo, S. Porcel, Dalton Trans. 45 (2016) 479-483.
[26]
K. Yang, B. Niu, Z. Ma, et al., J. Org. Chem. 84 (2019) 14045-14052.
[27]
P.A. Champagne, J. Desroches, J.D. Hamel, et al., Chem. Rev. 115 (2015) 9073-9174.
[28]
M.G. Campbell, T. Ritter, Chem. Rev. 115 (2015) 612-633.
[29]
J. Xu, Z. Kuang, Q. Song, Chin. Chem. Lett. 29 (2018) 963-966.
[30]
M.R.P. Heravi, Chin. Chem. Lett. 21 (2010) 1399-1402.
[31]
K. Yang, M. Song, A. Ali, et al., Chem. Asian J. 15 (2020) 729-741.
[32]
F.J.A. Troyano, K. Merkens, A. Gomez-Suarez, Asian J. Org. Chem. 9 (2020) 992-1007.
[33]
S. Stavber, Molecules 16 (2011) 6432-6464.
[34]
H. Mei, J. Liu, R. Pajkert, et al., Org. Biomol. Chem. 18 (2020) 3761-3766.
[35]
L. Niu, J. Liu, X.A. Liang, et al., Nature Commun. 10 (2019) 467-473.
[36]
Y. Kong, W. Xu, X. Liu, Chin. Chem. Lett. 31 (2020) 3245-3249.
[37]
Z. Cao, Q. Zhu, Y.W. Lin, et al., Chin. Chem. Lett. 30 (2019) 2132-2138.
[38]
H. Zhao, J. Jin, Org. Lett. 21 (2019) 6179-6184.
[39]
G. He, Y. Li, Z. Yu, et al., Org. Chem. Front. 6 (2019) 3644-3648.
[40]
B. Sun, W.P. Mai, L.R. Yang, et al., Chin. Chem. Lett. 26 (2015) 977-979.
[41]
K. Yang, Y. Li, Z. Ma, et al., Eur. J. Org. Chem. 2019 (2019) 5812-5814.
[42]
K. Yang, H. Zhang, B. Niu, et al., Eur. J. Org. Chem. 2018 (2018) 5520-5523.
[43]
L.Y. Xie, S. Peng, F. Liu, et al., Adv. Synth. Catal. 360 (2018) 4259-4264.
[44]
L.Y. Xie, J. Qu, S. Peng, et al., Green Chem. 20 (2018) 760-764.
[45]
Y. Chen, H. Qi, N. Chen, et al., J. Org. Chem. 84 (2019) 9044-9050.
[46]
X. Zhang, Y. Liao, R. Qian, et al., Org. Lett. 7 (2005) 3877-3880.
[47]
B. Sun, S. Yin, X. Zhuang, et al., Org. Biomol. Chem. 16 (2018) 6017-6024.
[48]
Y.H. Lv, K. Sun, W.Y. Pu, et al., RSC Adv. 6 (2016) 93486-93490.
[49]
D. Shi, H.T. Qin, C. Zhu, et al., Eur. J. Org. Chem. 2015 (2015) 5084-5088.
[50]
S. Chiba, H. Chen, Org. Biomol. Chem. 12 (2014) 4051-4060.
[51]
Z. Li, H. Li, X. Guo, et al., Org. Lett. 10 (2008) 803-805.
[52]
L. Wang, M. Zhang, Y. Zhang, et al., Chin. Chem. Lett. 31 (2020) 67-70.
[53]
S.C. Annedi, K. Majumder, L. Wei, et al., Bioorg. Med. Chem. 13 (2005) 2943-2958.
[54]
S.C. Annedi, W. Li, S. Samson, et al., J. Org. Chem. 68 (2003) 1043-1049.
Appendix
Less
Year 2021 volume 32 Issue 1
PDF
40
23
Cite this Article
BibTeX
Article Info
doi: 10.1016/j.cclet.2020.11.036
  • Receive Date：2020-09-25
  • Online Date：2026-01-04
  • Published：2021-01-15
Article Data
Affiliations
History
  • Received：2020-09-25
  • Revised：2020-11-09
  • Accepted：2020-11-11
Affiliations
    Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, School of Petrochemical Engineering, Changzhou University, Changzhou 213164, China
References
Share
https://castjournals.cast.org.cn/joweb/ccl/EN/10.1016/j.cclet.2020.11.036
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