Aza-Morita–Baylis–Hillman Reaction with Vinyl-oxadiazoles: An Expeditious Approach to Access New Heterocyclic Arrangements

Published as part of the ISySyCat2019 Special Issue

Abstract

In this communication, we disclosed a new aza-MBH reaction in which traditional nucleophilic partners of these reactions (e.g., acrylates, nitroolefins or enones) were replaced by vinyl-1,2,4-oxadiazoles. Thus, the aza-MBH reaction between 5-aryl-3-vinyl-1,2,4-oxadiazoles and N-sulfonylimines, catalyzed by the mixture DABCO/AcOH, provides a class of new adduct in yields varying from 31% up to 93% in reaction times from 30 minutes to 24 hours. Due to the biological activities and technological applications associated with the 1,2,4-oxadiazole motifs, this new class of heterocycles offers great synthetic and commercial potentiality.

Key words

vinyl-oxadiazoles - heterocycles - organocatalysis - Morita–Baylis–Hillman reaction - aza-Morita–Baylis–Hillman - nucleophilic partner

• References and Notes

• 1a Shi YL, Shi M. Eur. J. Org. Chem. 2007; 2905
• 1b Declerk V, Martinez J, Lamaty F. Chem. Rev. 2009; 109: 1
• 1c Drewes SE, Roos GH. P. Tetrahedron 1988; 44: 4653
• 2a Huang X, Xue J. J. Org. Chem. 2007; 72: 3965
• 2b Grychowska K, Kubica B, Drop M, Colacino E, Bantreil X, Pawłowski M, Martinez J, Subra G, Zajdel P, Lamaty F. Tetrahedron 2016; 72: 7462
• 2c Clary KN, Parvez M, Back TG. J. Org. Chem. 2010; 75: 3751
• 2d Grélaud S, Lusseau J, Massip S, Landais Y. Adv. Synth. Catal. 2017; 359: 2434
• 2e Basavaiah D, Rao AJ, Satyanarayana T. Chem. Rev. 2003; 103: 811
• 2f Basavaiah D, Rao PD, Hyma RS. Tetrahedron 1996; 52: 800
• 3 Perlmutter P, Teo CC. Tetrahedron Lett. 1984; 25: 5951
• 4a Shi M, Xu YM. Chem. Commun. 2001; 1876
• 4b Shi M, Xu YM, Zhao GL, Wu XF. Eur. J. Org. Chem. 2002; 3666
• 5 Shi M, Xu YM. Eur. J. Org. Chem. 2002; 696
• 6a Guan XY, Wei Y, Shi M. Eur. J. Org. Chem. 2010; 4098
• 6b Shen Y, Tang Q, Zhang C, Zhong W. Synlett 2012; 23: 741
• 7 Zhao GL, Huang JW, Shi M. Org. Lett. 2003; 5: 4737
• 8a Saunders LB, Cowen BJ, Miller SJ. Org. Lett. 2010; 12: 4800
• 8b Zhao GL, Shi M. J. Org. Chem. 2005; 70: 9975
• 9 Shi YL, Xu YM, Shi M. Adv. Synth. Catal. 2004; 346: 1220
• 10a Buscemi S, Pace A, Palumbo Piccionello A, Vivona N, Pani M. Tetrahedron 2006; 62: 1158
• 10b Back TG, Rankic DA, Sorbetti JM, Wulff JE. Org. Lett. 2005; 7: 2377
• 10c Clary KN, Back TG. Synlett 2007; 2995
• 10d Sorbetti JM, Clary KN, Rankic DA, Wulff JE, Parvez M, Back TG. J. Org. Chem. 2007; 72: 3326
• 10e Abermil N, Masson G, Zhu J. Org. Lett. 2009; 11: 4648
• 11 Wu Z, Zhou G, Zhou J, Guo W. Synth. Commun. 2006; 36: 2491
• 12 Chen J, Li J, Wang J, Li H, Wang W, Guo Y. Org. Lett. 2015; 17: 2214
• 13 Fernandes FS, Rodrigues MT, Zeoly LA, Conti C, Angolini CF. F, Eberlin MN, Coelho F. J. Org. Chem. 2018; 83: 15118
• 14 Watien F, Baker R, Engelstoff M, Herbert R, Macleod A, Knight A, Merchant K, Moseley J, Saunders J, Swain CJ, Wong E, Springer JP. J. Med. Chem. 1989; 32: 2282
• 15a Street LJ, Baker R, Castro JL, Chambers MS, Guiblin AR, Hobbs SC, Matassa VG, Reeve AJ, Beer MS, Middlemiss DN, Noble AJ, Stanton JA, Scholey K, Hargreaves RJ. J. Med. Chem. 1993; 36: 1529
• 15b Broadley KJ, Kelly DR. Molecules 2001; 6: 142
• 15c Csürös L. Ther. Hung. 1989; 37: 50
• 15d Ceyhan BB, Karakurt S. Respir. Med. 2002; 96: 61
• 16 Swain CJ, Baker R, Moseley J, Saunders J, Seward EM, Stevenson G, Kneen C, Beer M, Stanton J, Watling K. J. Med. Chem. 1991; 34: 140
• 17 Jones BJ, Costall B, Domeney AM, Kelly ME, Naylor RJ, Oakley NR, Tyers MB. Br. J. Pharmacol. 1988; 93: 985
• 18 Costall B, Domeney AM, Naylor RJ, Tyers MB. Br. J. Pharmacol. 1987; 92: 881
• 19a Pace A, Buscemi S, Piccionello AP, Pibiri I. Adv. Heterocycl. Chem. 2015; 116: 85
• 19b Pace A, Pierro P. Org. Biomol. Chem. 2009; 7: 4337
• 20a Ko D, Patel HA, Yavuz CT. Chem. Commun. 2015; 51: 2915
• 20b Agneeswari R, Tamilavan V, Song M, Kang JW, Jin SH, Hyun MH. J. Polym. Sci., Part A: Polym. Chem. 2013; 51: 2131
• 21a Joule JA, Mills K. Heterocyclic Chemistry, 5th ed. John Wiley & Sons; Chichester: 1990: 150
• 21b Cicchi S, Cordero FM, Giomi D. Prog. Heterocycl. Chem. 2007; 18: 288
• 21c Palumbo Piccionello A, Pace A, Buscemi S. Org. Lett. 2011; 13: 4749
• 21d Palumbo Piccionello A, Guarcello A, Buscemi S, Vivona N, Pace A. J. Org. Chem. 2010; 75: 8724
• 21e Zeng Z, Jin H, Xie J, Tian B, Rudolph M, Rominger F, Hashmi AS. K. Org. Lett. 2017; 19: 1020
• 21f Buscemi S, Pace A, Palumbo Piccionello A, Pibiri I, Vivona N, Giorgi G, Mazzanti A, Spinelli D. J. Org. Chem. 2006; 71: 8106
• 21g Strelnikova JO, Rostovskii NV, Starova GL, Khlebnikov AF, Novikov MS. J. Org. Chem. 2018; 83: 11232
• 22 Burns AR, Kerr JH, Kerr WJ, Passmore J, Paterson LC, Watson AJ. B. Org. Biomol. Chem. 2010; 8: 2777
• 23 Tata RR, Fu C, Kelley SP, Harmata M. Org. Lett. 2018; 20: 5723
• 24 Golushko AA, Khoroshilova OV, Vasilyev AV. J. Org. Chem. 2019; 84: 7495
• 25 General Procedure for the Synthesis of 1,2,4-Oxadiazole 1d²⁵ trans-β-Nitrostyrene 1 (2.0 mmol) was added to a mixture of TfOH (3.5 mL), CH₂Cl₂ (3.0 mL), and benzene (3.0 mmol) at –40 °C. After stirring at –40 °C for 1.5 h, the reaction mixture was poured at once into acrylonitrile (9.0 mmol) cooled to –30 °C. The resulting solution was heated to –20 °C and stirred at this temperature for 30 min, then quenched with water (30 mL) and extracted with CHCl₃ (3 × 30 mL). The combined organic phases were washed three times with water (40 mL) and dried with Na₂SO₄. The solvent was evaporated under the reduced pressure, and the residue was purified by chromatography column (hexane/EtOAc = 9:1); mp 53–55 °C. ¹H NMR (250 MHz, CDCl₃): δ = 7.53–7.27 (m, 10 H), 6.76 (dd, J = 17.7, 10.9 Hz, 1 H), 6.55 (dd, J = 17.7, 1.1 Hz, 1 H), 5.96 (dd, J = 10.9, 1.1 Hz, 1 H), 5.75 (s, 1 H). ¹³C NMR (63 MHz, CDCl₃): δ = 174.57, 172.11, 139.71, 128.92, 128.80, 128.73, 127.36, 120.68, 48.80. HRMS (ESI-TOF): m/z calcd for C₁₇H₁₅N₂O [M + H]⁺: 263.1179; found: 263.1189.
• 26 General Procedure for the Synthesis of Aza-Morita–Baylis–Hilman Adducts 3a–p In a 2mL flask equipped with a magnetic stir bar, oxadiazole (0.29 mmol), imine (0.32 mmol), and DABCO (34 mg, 0.30 mmol) were added sequentially. The atmosphere of the flask was exchanged for N₂, and then toluene (0.29 mL) and acetic acid (18 μL, 0.30 mmol) were added. The reaction was stirred at room temperature, and the time was specified for each substrate. After consumption of the starting material, as determined by TLC, the crude reaction was evaporated under reduced pressure. The residue was then purified by flash silica gel column chromatography (hexane/EtOAc = 9:1 to 7:3) to provide the aza-MBH adduct. N-{2-[3-(4-Methoxyphenyl)-1,2,4-oxadiazol-5-yl]-1-phenylprop-2-en-1-yl}benzenesulfonamide (3h) Purified by column chromatography (hexane/EtOAc = 8:2) to give 3h (100 mg, 0.22 mmol, 90%) as a white solid; mp 152–153 °C. ¹H NMR (500 MHz, CDCl₃): δ = 7.84 (d, J = 8.8 Hz, 2 H), 7.70 (d, J = 7.5 Hz, 2 H), 7.42 (t, J = 7.5 Hz, 1 H), 7.31 (t, J = 7.5 Hz, 2 H), 7.26–7.09 (m, 5 H), 6.90 (d, J = 8.8 Hz, 2 H), 6.22 (s, 1 H), 6.18 (d, J = 9.2 Hz, 1 H), 5.81 (s, 1 H), 5.53 (d, J = 9.2 Hz, 1 H), 3.79 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 172.8, 168.1, 162.3, 140.5, 137.9, 132.9, 132.2, 129.2, 129.0, 128.8, 128.3, 127.3, 126.7, 126.3, 118.7, 114.4, 59.9, 55.6. HRMS (ESI-TOF): m/z calcd for C₂₄H₂₂N₃O₄S⁺ [M + H]⁺: 448.1326; found: 448.1311. N-{2-[3-(4-Methoxyphenyl)-1,2,4-oxadiazol-5-yl]-1-(4-nitrophenyl)prop-2-en-1-yl}benzenesulfonamide (3i) Purified by column chromatography (hexane/EtOAc = 8:2) to give 3i (99 mg, 0.20 mmol, 81%) as a yellow oil. ¹H NMR (250 MHz, CDCl₃): δ = 8.12 (d, J = 8.5 Hz, 2 H), 7.89 (d, J = 8.5 Hz, 2 H), 7.79 (dd, J = 8.2, 1.5 Hz, 2 H), 7.54 (dd, J = 8.2, 6.6 Hz, 3 H), 7.42 (t, J = 7.5 Hz, 2 H), 6.98 (d, J = 8.5 Hz, 2 H), 6.62 (d, J = 9.6 Hz, 1 H), 6.34 (s, 1 H), 5.92 (s, 1 H), 5.70 (d, J = 9.6 Hz, 1 H), 3.88 (s, 2 H). ¹³C NMR (63 MHz, CDCl₃): δ = 172.14, 168.17, 162.49, 147.77, 145.23, 140.26, 133.31, 131.19, 127.79, 127.41, 127.20, 123.99, 118.29, 114.57, 59.65, 55.63. HRMS (ESI-TOF): m/z calcd for C₂₄H₂₁N₄O₆S⁺ [M + H]⁺: 493.1176; found: 493.1188. N-{[1-(4-Bromophenyl)-2-[3-(diphenylmethyl)-1,2,4-oxadiazol-5-yl]prop-2-en-1-yl}benzenesulfonamide (3m) Purified by column chromatography (hexane/EtOAc = 8:2 to 7:3) to give 3m (103 mg, 0.18 mmol, 93%) as a colorless oil. ¹H NMR (250 MHz, CDCl₃): δ = 7.56–7.43 (m, 3 H), 7.40–7.20 (m, 12 H), 7.18–7.04 (m, 4 H), 6.27–6.13 (m, 2 H), 5.88 (s, 1 H), 5.56 (s, 1 H), 5.49 (d, J = 9.7 Hz, 1 H). ¹³C NMR (63 MHz, CDCl₃): δ = 172.48, 171.29, 140.14, 139.49, 138.98, 136.89, 132.77, 131.70, 131.40, 128.81, 128.76, 128.66, 128.64, 128.59, 128.26, 127.59, 127.42, 126.99, 126.42, 122.10, 59.58, 48.09. HRMS (ESI-TOF): m/z calcd for C₃₀H₂₅BrN₃O₃S⁺ [M + H]⁺: 586.0795; found: 586.0784.
• 27 Iwabuchi Y, Nakatani M, Yokoyama N, Hatakeyama S. J. Am. Chem. Soc. 1999; 121: 10219 . Reactions were carried out with vinyl-oxadiazole 1a (0.16 mmol), N-sulfonylimine 2a (0.17 mmol), and β-isocupreidine (0.016 mmol)²⁵ as chiral catalyst. So far the best conditions found led to an enantiomeric ratio of 68.5:31.5