DBU-Mediated Dimerization: Facile Access to 9,9′-Bifluorenylidenes and Isoindigos

Abstract

The present work describes the 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)-promoted self-dimerization of 9-chlorofluorenes and 3-chlorooxindoles for the preparation of the corresponding 9,9′-bifluorenylidene and isoindigo derivatives in moderate to good yields of 29–97%. The reactions proceed readily in a short reaction time under mild and metal-free conditions. Scale-up syntheses (5.0 mmol) of selected 9,9′-bifluorenylidene derivatives proceed in decent yields, highlighting the synthetic utility of the reported protocol.

Key words

9,9′-bifluorenylidenes - isoindigos - 9-chlorofluorenes - 3-chlorooxindoles - dimerization

Publikationsverlauf

Eingereicht: 30. Juli 2023

Angenommen nach Revision: 22. August 2023

Accepted Manuscript online:
22. August 2023

Artikel online veröffentlicht:
28. September 2023

• References

• 1a Brunetti FG, Gong X, Tong M, Heeger AJ, Wudl F. Angew. Chem. Int. Ed. 2010; 49: 532 ; Angew. Chem. 2010, 122, 542
• 1b Gong X, Tong M, Brunetti FG, Seo J, Sun Y, Moses D, Wudl F, Heeger AJ. Adv. Mater. 2011; 23: 2272
• 1c Sui M.-Y, Geng Y, Sun G.-Y, Wang J.-P. J. Mater. Chem. C 2017; 5: 10343
• 2 Kim HU, Kim J.-H, Suh H, Kwak J, Kim D, Grimsdale AC, Yoon SC, Hwang D.-H. Chem. Commun. 2013; 49: 10950
• 3a Levy A, Goldschmidt M, Agranat I. Lett. Org. Chem. 2006; 3: 579
• 3b Liu J, Wang Y. Opt. Express 2012; 20: 14596
• 3c Park OY, Kim HU, Kim J.-H, Park JB, Kwak J, Shin WS, Yoon SC, Hwang D-H. Sol. Energy Mater Sol. Cells 2013; 116: 275
• 3d Conyard J, Heisler IA, Browne WR, Feringa BL, Amirjalayer S, Buma WJ, Woutersen S, Meech SR. J. Phys. Chem. A 2014; 118: 5961
• 3e Rakstys K, Saliba M, Gao P, Gratia P, Kamarauskas E, Paek S, Jankauskas V, Nazeeruddin MK. Angew. Chem. Int. Ed. 2016; 55: 7464
• 3f Minaki H, Kawata S, Furudate J, Saito A, Katagiri H, Pu Y.-J. Chem. Lett. 2017; 46: 1126
• 3g Zhao Y, Wang H, Xia S, Zhou F, Luo Z, Luo J, He F, Yang C. Chem. Eur. J. 2018; 24: 4149
• 3h Zhang T, Yu T, Zhao Y, Wei C, Ma H, Li Y, Zhang H. Dyes Pigm. 2020; 177: 108233
• 3i Xu J. New J. Chem. 2020; 44: 3566
• 3j Zhu X, Liu F, Ba X, Wu Y. Org. Lett. 2022; 24: 5851
• 3k Aguilar-Enriquez X, Skala LP, Dichtel WR. J. Org. Chem. 2022; 87: 16307
• 4 Assadi N, Pogodin S, Agranat I. Eur. J. Org. Chem. 2011; 6773
• 5 Zhang L, Yu X, Zhang L, Zhou X, Lin Y. Org. Chem. Front. 2014; 1: 929
• 6 Knappke CE. I, Arduengo AJ, Jiao H, Neudörfl J, von Wangelin AJ. Synthesis 2011; 23: 3784
• 7a Zhao J, Asao N, Yamamoto Y, Jin T. J. Am. Chem. Soc. 2014; 136: 9540
• 7b Zhang M, Deng W, Sun M, Zhou L, Deng G, Liang Y, Yang Y. Org. Lett. 2021; 23: 5744
• 8 Xu J, Takai A, Bannaron A, Nakagawa T, Matsuo Y, Sugimoto M, Matsushita Y, Takeuchi M. Mater. Chem. Front. 2018; 2: 780
• 9 Wilming FM, Marazzi B, Debes PP, Becker J, Schreiner PR. J. Org. Chem. 2023; 88: 1024
• 10a Randell NM, Kelly TL. Chem. Rec. 2019; 19: 973
• 10b Bogdanov AV, Mironov VF. Beilstein J. Org. Chem. 2021; 17: 1533
• 10c Wei X, Zhang W, Yu G. Adv. Funct. Mater. 2021; 31: 2010979
• 11a Sassatelli M, Bouchikhi F, Aboab B, Anizon F, Fabbro D, Prudhomme M, Moreau P. Anti-Cancer Drugs 2007; 18: 1069
• 11b Xiao Z, Wang Y, Lu L, Li Z, Peng Z, Han Z, Hao Y. Leukocyte Res. 2006; 30: 54
• 11c Bouchikhi F, Anizon F, Moreau P. Eur. J. Med. Chem. 2008; 43: 755
• 11d Wee XK, Yeo WK, Zhang B, Tan VB. C, Lim KM, Tay TE, Go M.-L. Bioorg. Med. Chem. 2009; 17: 7562
• 11e Zhao P, Li Y, Gao G, Wang S, Yan Y, Zhan X, Liu Z, Mao Z, Chen S, Wang L. Eur. J. Med. Chem. 2014; 86: 165
• 12a Bogdanov AV, Musin LI, Mironov VF. ARKIVOC 2015; (vi): 362
• 12b Liu M, Qiu S, Ye Y, Yin G. Tetrahedron Lett. 2016; 57: 5856
• 13 Yao X, Wang T, Zhang Z. Eur. J. Org. Chem. 2018; 4475
• 14a Yang X.-H, Li K, Song R.-J, Li J.-H. Eur. J. Org. Chem. 2014; 616
• 14b Li G, Zhou G, Zhang-Negrerie D, Du Y, Huang J, Zhao K. Adv. Synth. Catal. 2016; 358: 3534
• 14c Liu L, Song L, Guo Y, Min D, Shi T, Zhang W. Tetrahedron 2018; 74: 354
• 15 Bergman J, Romero I. J. Heterocycl. Chem. 2010; 47: 1215
• 16 Shermolovich YG, Emets SV, Tolmachev AA. Chem. Heterocycl. Compd. 2003; 8: 1076
• 17 Zhang H.-H, Wang L.-Q, Huang L.-T, Zhu L.-Q, Feng Y.-Y, Lu L.-M, Zhao Q.-Y, Wang X.-Q, Wang Z. Chem. Commun. 2018; 54: 8265
• 18 Zhao S, Gao N, Bao N, Qian M, Chen Z.-Y, Zhang M.-J, Chen X. J. Org. Chem. 2022; 87: 11826
• 19 Jagtap RA, Pradhan C, Gonnade RG, Punji B. Chem. Asian J. 2022; 17: e202200414
• 20 Rastogi GK, Deka B, Deb ML, Baruah PK. Asian J. Org. Chem. 2022; 11: e202100757
• 21 Meesin J, Chotsaeng N, Kuhakarn C. Synlett 2022; 33: 1317
• 22a Zheng P.-F, Ouyang Q, Niu S.-L, Shuai L, Yuan Y, Jiang K, Liu T.-Y, Chen Y.-C. J. Am. Chem. Soc. 2015; 137: 9390
• 22b Chen L, He J. J. Org. Chem. 2020; 85: 5203
• 23 9,9′-Bifluorenylidenes (2); General Procedure To a solution of 9-chlorofluorene 1 (0.5 mmol) in DMSO (2 mL) was added DBU (0.15 mL, 1.0 mmol). The reaction mixture was stirred at room temperature for 2 h. After completion of the reaction, the mixture was diluted with EtOAc (20 mL) and washed with H₂O (2 × 30 mL) to remove DMSO. The EtOAc layer was then washed with brine, dried over anhydrous Na₂SO₄, and filtered. The solvent was evaporated under reduced pressure and the crude residue was purified by column chromatography using silica gel and 10% DCM in hexane as the eluent. Di-tert-butyl [9,9′-Bifluorenylidene]-2,2'-diyl(E)-dicarbamate (2c) Yield: 0.0535 g (38%); orange solid, mp 183–184 °C. ¹H NMR (500 MHz, CDCl₃): δ = 8.46–8.28 (m, 4 H), 7.64–7.51 (m, 4 H), 7.43–7.34 (m, 2 H), 7.28 (td, J = 7.4, 1.0 Hz, 2 H), 7.22–7.19 (m, 2 H), 7.14 (td, J = 7.6, 1.2 Hz, 2 H), 1.53 (s, 18 H). ¹³C NMR (126 MHz, CDCl₃): δ = 153.8, 141.5, 140.8, 138.6, 138.1, 136.9, 136.9, 129.4, 126.9, 126.3, 121.3, 120.4, 119.8, 119.6, 80.4, 28.7. HRMS (ESI): m/z [M + H]⁺ calcd for C₃₆H₃₅N₂O₄: 559.2957; found: 559.2554. Di-tert-butyl [9,9′-Bifluorenylidene]-2,2'-diyl(Z)-dicarbamate (2c) Yield: 0.0648 g (46%); red solid; mp 178–180 °C. ¹H NMR (500 MHz, CDCl₃): δ = 8.23 (d, J = 7.8 Hz, 2 H), 8.15 (t, J = 1.2 Hz, 2 H), 7.50 (d, J = 7.5 Hz, 2 H), 7.46–7.37 (m, 4 H), 7.27–7.20 (m, 2 H), 7.13–7.07 (m, 2 H), 6.51 (s, 2 H), 1.52 (s, 18 H). ¹³C NMR (126 MHz, CDCl₃): δ = 152.8, 141.3, 141.1, 138.9, 138.4, 137.5, 136.4, 129.1, 126.5, 126.3, 120.3, 119.5, 116.6, 81.3, 28.6. HRMS (ESI): m/z [M + H]⁺ calcd for C₃₆H₃₅N₂O₄: 559.2957; found: 559.2580. 2,2′,7,7′-Tetrakis(allyloxy)-9,9′-bifluorenylidene (2f) Yield: 0.1354 g (97%); brown solid; mp 159–161 °C. ¹H NMR (500 MHz, CDCl₃): δ = 7.95 (d, J = 1.4 Hz, 4 H), 7.43 (d, J = 5.0 Hz, 4 H), 6.86 (dd, J = 4.9, 1.4 Hz, 4 H), 6.02 (ddt, J = 10.4, 6.3, 3.2 Hz, 4 H), 5.38 (d, J = 1.0 Hz, 4 H), 5.25 (dd, J = 6.3, 0.9 Hz, 4 H), 4.49 (d, J = 3.2 Hz, 8 H). ¹³C NMR (126 MHz, CDCl₃): δ = 157.7, 141.7, 139.6, 135.3, 133.4, 119.9, 117.9, 116.9, 112.9, 69.4. HRMS (ESI): m/z [M + H]⁺ calcd for C₃₈H₃₃O₄: 553.2379; found: 553.2371.
• 24 Isoindigos (4); General Procedure To a solution of 3-chlorooxindole 3 (0.5 mmol) in 1,4-dioxane (2 mL) was added DBU (0.15 mL, 1.0 mmol). The reaction mixture was stirred at room temperature for 0.5–1 h. After completion of the reaction, the mixture was diluted with H₂O (20 mL) and extracted with EtOAc (2 × 20 mL). The EtOAc layer was then washed with brine, dried over anhydrous Na₂SO₄ and filtered. The solvent was evaporated under reduced pressure and the crude residue was purified by column chromatography using silica gel and 20% EtOAc in hexane as the eluent. (E)-1,1′-Diallyl-[3,3′-biindolinylidene]-2,2′-dione (4a) Yield: 0.0255 g (57%); red solid, mp 161–162 °C. ¹H NMR (500 MHz, CDCl₃): δ = 9.20 (dd, J = 8.1, 1.2 Hz, 2 H), 7.34 (td, J = 7.7, 1.2 Hz, 2 H), 7.06 (td, J = 7.8, 1.2 Hz, 2 H), 6.78 (dd, J = 7.8, 1.1 Hz, 2 H), 5.88 (ddt, J = 17.2, 10.3, 5.2 Hz, 2 H), 5.31–5.20 (m, 4 H), 4.43 (d, J = 5.2 Hz, 4 H). ¹³C NMR (126 MHz, CDCl₃): δ = 167.8, 144.6, 133.5, 132.5, 131.3, 130.1, 122.5, 121.7, 117.7, 108.6, 42.4. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₂H₁₉N₂O₂: 343.1447; found: 343.1443. (E)-1,1′-Diallyl-5,5′-difluoro-[3,3′-biindolinylidene]-2,2′-dione (4g) Yield: 0.0395 g (40%); black solid, mp 176–177 °C. ¹H NMR (500 MHz, CDCl₃): δ = 9.12 (dd, J = 10.8, 2.7 Hz, 2 H), 7.08 (td, J = 8.4, 2.7 Hz, 2 H), 6.70 (dd, J = 8.6, 4.5 Hz, 2 H), 5.90–5.82 (m, 2 H), 5.37–5.13 (m, 4 H), 4.42 (dt, J = 5.2, 1.7 Hz, 4 H). ¹³C NMR (126 MHz, CDCl₃) δ = 167.5, 158.66 (d, J_C–F = 237.6 Hz), 141.0, 134.0, 131.0, 122.2 (d, JC–F = 9.9 Hz), 119.2 (d, JC–F = 24.5 Hz), 118.0, 117.8 (d, JC–F = 27.7 Hz), 108.8 (d, JC–F = 8.1 Hz), 42.6. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₂H₁₇F₂N₂O₂: 379.1258; found: 379.1255.