Copper-Promoted Dimerization of Benzyl Thiocyanates to Access Functionalized Bibenzyls

Abstract

The synthesis of bibenzyl derivatives holds significance in organic chemistry due to their diverse pharmacological and synthetic applications. Herein, we report a novel copper-promoted dimerization reaction for the efficient synthesis of functionalized bibenzyls from benzyl thiocyanates. The coupling reaction proceeds under aerobic and mild conditions through a cascade C–S bond cleavage in one pot. Diverse substituents, including electron-withdrawing groups on the aryl ring, are well tolerated to afford the desired products in moderate to good yields. The developed protocol could be utilized to obtain the cross-coupling product from two different electron-deficient benzyl thiocyanates.

Key words

bibenzyls - benzyl thiocyanates - homocoupling - cross-coupling - C–S bond cleavage

Publication History

Received: 27 February 2024

Accepted after revision: 21 May 2024

Accepted Manuscript online:
21 May 2024

Article published online:
04 June 2024

• References and Notes

• 1 Li C.-J. Chem. Rev. 2005; 105: 3095
• 2 Hassan J, Sévignon M, Gozzi C, Schulz E, Lemaire M. Chem. Rev. 2002; 102: 1359
• 3 Ravelli D, Protti S, Fagnoni M. Chem. Rev. 2016; 116: 9850
• 4 Grirrane A, Corma A, García H. Science. 2008; 322: 1661
• 5 Czaplik WM, Mayer M, Jacobi von Wangelin A. Angew. Chem. Int. Ed. 2008; 48: 607
• 6 Zhu X, Lin Y, San Martin J, Sun Y, Zhu D, Yan Y. Nat. Commun. 2019; 10: 2843
• 7 Song Y, Hwang S, Gong P, Kim D, Kim S. Org. Lett. 2007; 10: 269
• 8 Yamamura K, Ono S, Tabushi I. Tetrahedron Lett. 1988; 29: 1797
• 9 Harrowven DC, Kostiuk SL. Nat. Prod. Rep. 2012; 29: 223
• 10 Prier CK, Rankic DA, MacMillan DW. Chem. Rev. 2013; 113: 5322
• 11 He L, Su Q, Bai L, Li M, Liu J, Liu X, Zhang C, Jiang Z, He J, Shi J, Huang S, Guo L. Eur. J. Med. Chem. 2020; 204: 112530
• 12 Barrett TN, Braddock DC, Monta A, Webb MR, White AJ. P. J. Nat. Prod. 2011; 74: 1980
• 13 Liu J, Li B. Synth. Commun. 2007; 37: 3273
• 14a Gharbi-Benarous J, Morales-Rios MS, Dana G. J. Org. Chem. 1984; 49: 2039
• 14b Pan F.-F, Guo P, Huang X, Shu X.-Z. Synthesis 2021; 53: 3094
• 15 Gilman H, Gorsich RG. J. Am. Chem. Soc. 1955; 77: 3134
• 16a Cahiez G, Moyeux A, Buendia J, Duplais C. J. Am. Chem. Soc. 2007; 129: 13788
• 16b Kim S.-H, Rieke RD. J. Org. Chem. 2000; 65: 2322
• 16c Suh Y, Lee J.-s, Kim S.-H, Rieke RD. J. Organomet. Chem. 2003; 684: 20
• 17 Ranu BC, Dutta P, Sarkar A. Tetrahedron Lett. 1998; 39: 9557
• 18a Barrero AF, Herrador MM, Quilez del Moral JF, Arteaga P, Akssira M, El Hanbali F, Arteaga JF, Diéguez HR, Sánchez EM. J. Org. Chem. 2007; 72: 2251
• 18b Qian Y, Li G, Zheng X, Huang Y.-Z. Synlett 1991; 489
• 19a Girard P, Namy JL, Kagan HB. J. Am. Chem. Soc. 1980; 102: 2693
• 19b Liu Y, Zhang D, Xiao S, Qi Y, Liu S. Asian J. Org. Chem. 2019; 8: 858
• 20 Sato K, Inoue Y, Mori T, Sakaue A, Tarui A, Omote M, Kumadaki I, Ando A. Org. Lett. 2014; 16: 3756
• 21 Chen S.-Y, Zhang J, Li Y.-H, Wen J, Bian S.-Q, Yu X.-Q. Tetrahedron Lett. 2009; 50: 6795
• 22 Levin VV, Agababyan DP, Struchkova MI, Dilman AD. Synthesis 2018; 50: 2930
• 23 Lanterna AE, Elhage A, Scaiano JC. Catal. Sci. Technol. 2015; 5: 4336
• 24 Li Y, Ren P, Zhang D, Qiao W, Wang D, Yang X, Wen X, Rummeli MH, Niemantsverdriet H, Lewis JP, Besenbacher F, Xiang H, Li Y, Su R. ACS Catal. 2021; 11: 4338
• 25 Yang Q, Li X, Chen L, Han X, Wang FR, Tang J. Angew. Chem. Int. Ed. 2023; 62: e202307907
• 26 Zhao X, Li M, Sun K, Xu Z, Tian L, Wang Y. Chem. Commun. 2023; 59: 13062
• 27 Seong CM, Ansel AQ, Roberts CC. J. Org. Chem. 2023; 88: 3935
• 28 Singh, S.; De, S. R. unpublished results.
• 29 1,2-Diphenylethane (2a); Typical ProcedureBnSCN (1a) (0.67 mmol, 1 equiv), CuBr (0.33 mmol, 0.5 equiv), and Cs₂CO₃ (0.67 mmol, 1 equiv) were dissolved in dry MeCN (2 mL) in a 5 mL Teflon-screw-capped vial, and the mixture was stirred at 90 °C for 12 h under air. When the reaction was complete (TLC), the solvent was removed under reduced pressure, the residue was extracted with EtOAc (2 × 40 mL), and the extracts were washed with H₂O (2 × 20 mL). The combined organic layer was washed with brine (2 × 15 mL), dried (Na₂SO₄), filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography [silica gel, PE–EtOAc (20:1)] to give a white solid; yield:105 mg (86%). ¹H NMR (400 MHz, CDCl₃): δ = 7.30 (dd, J = 6.8, 1.3 Hz, 4 H), 7.29–7.25 (m, 2 H), 7.25–7.22 (m, 4 H), 3.59 (s, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 137.5 (2 C), 129.5 (4 C), 128.6 (4 C), 127.5 (2 C), 43.4 (2 C). These values agree with those reported in the literature.14b