Synthesis of Unsymmetrical Aza[7]helicenes by One-Pot Wittig–Heck and Photodehydrogenation Sequence

We dedicate this paper to Professor Pradeep Kumar of National Chemical Laboratory (Pune, India) on the occasion of his 60^th birthday

Abstract

An efficient protocol for the synthesis of unsymmetrical aza[7]helicenes has been developed. The bis-styryl-type substrates for regiospecific photodehydrogenative oxidative double cyclization to give helicenes were prepared by a one-pot Wittig–Heck sequence as well as a stepwise procedure. The derivatives were characterized by single-crystal X-ray diffraction analysis and fluorescence spectroscopy.

Key words

helical compounds - aza[7]helicenes - one-pot synthesis - Wittig reaction - Heck reaction - photocyclodehydrogenation.

• References and Notes

• 1a Grimme S. Harren J. Sobanski A. Vögtle F. Eur. J. Org. Chem. 1998; 1491
• 1b Urbano A. Angew. Chem. Int. Ed. 2003; 42: 3986
• 1c Collins SK. Vachon MP. Org. Biomol. Chem. 2006; 4: 2518
• 1d Rajca A. Miyasaki M. In Functional Organic Materials . Muller TJ. J. Bunz UH. F. Wiley-VCH; Weinheim: 2007: 547
• 1e Shen Y. Chen C.-F. Chem. Rev. 2012; 112: 1463
• 1f Gingras M. Chem. Soc. Rev. 2013; 42: 968
• 1g Gingras M. Félix G. Peresutti R. Chem. Soc. Rev. 2013; 42: 1007
• 1h Gingras M. Chem. Soc. Rev. 2013; 42: 1051
• 1i Chen C.-F. Shen Y. In Helicene Chemistry: From Synthesis to Applications: Springer: Berlin, 2017.
• 2a Caronna T. Sinisi R. Catellani M. Malpezzi L. Meille SV. Mele A. Chem. Commun. 2000; 1139
• 2b Collins SK. Vachon MP. Org. Biomol. Chem. 2006; 4: 2518
• 3a Shyam Sundar M. Bedekar AV. Org. Lett. 2015; 17: 5808
• 3b Sako M. Takeuchi Y. Tsujihara T. Kodera J. Kawano T. Takizawa S. Sasai H. J. Am. Chem. Soc. 2016; 138: 11481
• 3c Hasan M. Khose VN. Mori T. Borovkov V. Karnik AV. ACS Omega 2017; 2: 592 ; and references cited therein
• 4 Oyama H. Nakano K. Harada T. Kuroda R. Naito M. Nobusawa K. Nozaki K. Org. Lett. 2013; 15: 2104
• 5 Nakano K. Oyama H. Nishimura Y. Nakasako S. Nozaki K. Angew. Chem. Int. Ed. 2012; 51: 695
• 6a Abbate S. Bazzini C. Caronna T. Fontana F. Gambarotti C. Gangemi F. Longhi G. Mele A. Sora IN. Panzeri W. Tetrahedron 2006; 62: 139
• 6b Waghray D. Zhang J. Jacobs J. Nulens W. Basaric N. van Meervelt L. Dehaen W. J. Org. Chem. 2012; 77: 10176
• 6c Kaneko E. Matsumoto Y. Kamikawa K. Chem. Eur. J. 2013; 19: 11837
• 6d Zheng Y.-H. Lu H.-Y. Li M. Chen C.-F. Eur. J. Org. Chem. 2013; 3059
• 6e Weimer M. Da Costa RC. Lee F.-H. Fuchter MJ. Org. Lett. 2013; 15: 1706
• 6f Sonawane MR. Vávra J. Šaman D. Císařová I. Teplý F. Synthesis 2015; 47: 3479
• 6g Zhang X. Clennan EL. Petek T. Weber J. Tetrahedron 2017; 73: 508
• 6h Otani T. Tsuyuki A. Iwachi T. Someya S. Tateno K. Kawai H. Saito T. Kanyiva KS. Shibata T. Angew. Chem. Int. Ed. 2017; 56: 3906 ; and references cited therein
• 7a Meisenheimer J. Witte K. Ber. Dtsch. Chem. Ges. 1903; 36: 4153
• 7b Fuchs W. Niszel F. Ber. Dtsch. Chem. Ges. 1927; 60: 209
• 7c Pichel I. Grimme S. Kotila S. Nieger M. Vögtle F. Tetrahedron: Asymmetry 1996; 7: 109
• 8a Shi L. Liu Z. Dong G. Duan L. Qiu Y. Jia J. Guo W. Zhao D. Cui D. Tao X. Chem. Eur. J. 2012; 18: 8092
• 8b Hua W. Liu Z. Duan L. Dong G. Qiu Y. Zhang B. Cui D. Tao X. Cheng N. Liu Y. RSC Adv. 2015; 5: 75
• 9a Kötzner L. Webber MJ. Martínez A. De Fusco C. List B. Angew. Chem. Int. Ed. 2014; 53: 5202
• 9b Bucinskas A. Waghray D. Bagdziunas G. Thomas J. Grazulevicius JV. Dehaen W. J. Org. Chem. 2015; 80: 2521
• 9c Chen T. Zhang B. Liu Z. Duan L. Dong G. Feng Y. Luo X. Cui D. Tetrahedron Lett. 2017; 58: 531
• 10a Nakano K. Hidehira Y. Takahashi K. Hiyama T. Nozaki K. Angew. Chem. Int. Ed. 2005; 44: 7136
• 10b Waghray D. Cloet A. van Hecke K. Mertens SF. L. De Feyter S. van Meervelt L. van der Auweraer M. Dehaen W. Chem. Eur. J. 2013; 19: 12077
• 10c Braiek MB. Aloui F. Moussa S. Tounsi M. Marrot J. Hassine BB. Tetrahedron Lett. 2013; 54: 5421
• 11a Upadhyay GM. Talele HR. Sahoo S. Bedekar AV. Tetrahedron Lett. 2014; 55: 5394
• 11b Upadhyay GM. Bedekar AV. Tetrahedron 2015; 71: 5644
• 12 Upadhyay GM. Talele HR. Bedekar AV. J. Org. Chem. 2016; 81: 7751
• 13a Moorthy JN. Mandal S. Mukhopadhyay A. Samanta S. J. Am. Chem. Soc. 2013; 135: 6872
• 13b Jhulki S. Mishra AK. Chow TJ. Moorthy JN. Chem. Eur. J. 2016; 22: 9375
• 13c Mousawi AA. Dumur F. Garra P. Toufaily J. Hamieh T. Goubard F. Bui T.-T. Graff B. Gigmes D. Fouassier JP. Lalevée J. J. Polym. Sci., Part A: Polym. Chem. 2017; 55: 1189
• 14a Martin RH. Schurter JJ. Tetrahedron Lett. 1969; 10: 3679
• 14b Wynberg H. Acc. Chem. Res. 1971; 4: 65
• 14c Talele HR. Gohil MJ. Bedekar AV. Bull. Chem. Soc. Jpn. 2009; 82: 1182
• 15a Saiyed AS. Bedekar AV. Tetrahedron Lett. 2010; 51: 6227
• 15b Patel HA. Patel AL. Bedekar AV. Appl. Organometal. Chem. 2015; 29: 1
• 16a Buu-Hoi NP. Hoán N. J. Am. Chem. Soc. 1951; 73: 98
• 16b Zhao T. Liu Z. Song Y. Xu W. Zhang D. Zhu D. J. Org. Chem. 2006; 71: 7422
• 17 Fedorova OA. Andryukhina EN. Gromov SP. Synthesis 2003; 371
• 18 Experimental Details Synthesis of 9-Butyl-3-(4-methylstyryl)-6-(styryl)-9H-carbazole (4a) by One-Pot Wittig–Heck Reaction A catalyst solution was prepared under nitrogen atmosphere using Pd(OAc)₂ (0.010 g, 0.045 mmol, 1 mol%) and dppp (0.037 g, 0.091 mmol, 2 mol %) in DMA (5 mL) at r.t. with constant stirring until a homogenous solution was obtained. A two-necked round-bottom flask was charged with 6-bromo-9-butyl-9H-carbazole-3-carbaldehyde (1, 1.500 g, 4.54 mmol), 4-methyl styrene (3x, 0.640 g, 5.450 mmol), benzyltriphenylphosphonium chloride (2x, 2.120 g, 5.450 mmol), dry K₂CO₃ (2.510 g, 18.200 mmol), TBAB (0.290 g, 0.908 mmol, 20 mol%), and DMA (10 mL), and the mixture was heated up to 100 °C. At 100 °C, the catalyst solution was added dropwise, and the mixture was heated to 140 °C for 48 h. After the completion of the reaction, the mixture was poured into water and extracted with EtOAc (3 × 100 mL). The combined organic phase was washed with water, brine, and dried over anhydrous Na₂SO₄. The solvent was removed under reduced pressure, and the crude product was purified by column chromatography on silica gel using PE–EtOAc (95:5) as eluent to afford cis-trans isomers of the compound 4a (0.92 g; 46%); R_f = 0.5 (5:95 EtOAc–PE). Physical state: white crystalline solid; mp 178–180 °C. IR (KBr): 3423, 3016, 2947, 1863, 1596, 1489, 1388, 1349, 1306, 1250, 1179, 1116, 1038, 970, 861, 823, 750 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 8.28 (d, J = 3.2 Hz, 2 H), 7.70–7.67 (m, 2 H), 7.60–7.58 (d, J = 7.6 Hz, 2 H), 7.50–7.48 (d, J = 8.0 Hz, 2 H), 7.16 (d, J = 16.4 Hz), 7.12–7.08 (d, J = 16.4 Hz, 2 H), 6.93–6.91 (br d, 4 H), 4.32 (t, J = 7.2 Hz, 2 H), 2.4 (s, 3 H), 1.93–1.86 (m, 2 H), 1.47–1.38 (m, 2 H), 0.97 (t, J = 7.2 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 140.73, 140.53, 136.95, 136.48, 135.12, 132.47, 130.19, 129.43, 129.02, 128.82, 128.50, 128.32, 127.37, 126.19, 126.16, 124.74, 124.66, 124.63, 123.28, 123.19, 118.79, 118.51, 109.12, 43.08, 31.20, 21.30, 20.57, 13.93. General Procedure for Photocyclodehydrogenation Synthesis of 2-Methyl-9-butyl-9H-aza[7]helicene (6a) A solution of 3,6-distyryl-N-butylcarbazole (4a, 0.200 g, 0.45 mmol), iodine (0.253 g, 0.99 mmol), dry THF (3.26 g, 3.67 mL, 45.3 mmol), and toluene (610 mL) was irradiated using a 250 W HPMV lamp (10 h monitored by TLC). After the completion of the reaction, the excess of iodine was removed by washing the solution with aq Na₂S₂O₃ and water. The organic layer was concentrated under reduced pressure to obtain the crude product. The crude product was purified by column chromatography over silica gel using PE–EtOAc (98:2) as eluent to obtain a pale yellow solid (0.06 g; 30%). R_f = 0.4 (EtOAc–PE = 5:95). Physical state: yellow solid; mp >200 °C. IR (KBr): 3427, 3042, 2952, 2927, 2867, 1725, 1660, 1588, 1522, 1495, 1450, 1339, 1283, 1218, 795, 746, 645 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 8.14 (d, J = 8.8 Hz, 2 H), 8.06 (d, J = 8.4 Hz, 2 H), 7.99–7.96 (m, 3 H), 7.90–7.88 (d, J = 8.4 Hz, 1 H), 7.83–7.79 (m, 2 H), 7.75 (d, J = 8.0 Hz, 1 H), 7.40 (d, J = 8.4 Hz, 1 H), 7.22–7.18 (m, 2 H), 7.05–7.03 (dd, J = 8.0, 1.2 Hz, 1 H), 6.28–6.24 (m, 1 H), 4.79 (t, J = 7.2 Hz, 2 H), 1.44 (s, 3 H), 1.04 (t, J = 7.2 Hz, 3 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 139.23, 132.47, 131.49, 130.11, 129.91, 129.43, 128.34, 127.74, 127.43, 127.20, 126.82, 126.73, 126.61, 126.57, 126.53, 126.40, 126.14, 126.10, 125.91, 125.78, 124.03, 123.96, 122.34, 120.18, 116.75, 116.70, 109.57, 109.45, 43.44, 31.96, 20.77, 20.71, 13.98 ppm. HRMS (ESI-TOF): m/z calcd for C₃₃H₂₇N: 437.2143; found: 437.2140. The spectral and analytical data of other compounds are presented in the Supporting Information.