Visible-Light-Promoted Click [3+2] Cycloaddition of Aziridine with Alkyne: An Efficient Synthesis of Dihydropyrrolidine

Abstract

A photocatalytic [3+2] cycloaddition of aziridines with activated alkynes is reported under visible-light irradiation in the presence of ruthenium catalyst. This chemical transformation provides polysubstituted pyrrolidines in good yields based on the click chemistry philosophy. The reaction successfully represents a primary trial of cyclocarboamination through photocascade catalysis combining energy transfer and redox neutral reactions.

Key words

aziridine - alkyne - dihydropyrrolidine - visible light - click chemistry - photoredox catalysis

Publication History

Received: 20 February 2023

Accepted after revision: 24 May 2023

Accepted Manuscript online:
24 May 2023

Article published online:
26 June 2023

• References and Notes

• 1a Smalley RK. In Comprehensive Heterocyclic Chemistry, Vol. 7. Katritzky AR, Rees CW. Pergamon Press; Oxford: 1984: 491-546
• 1b Leimgruber W, Stefanovic V, Schenker F, Karr A, Berger J. J. Am. Chem. Soc. 1965; 87: 5791
• 1c Zaman L, Arakawa O, Shimosu A, Onoue Y, Nishio S, Shida Y, Noguchi T. Toxicon 1997; 35: 205
• 1d Komoda T, Sugiyama Y, Abe N, Imachi M, Hirota H, Hirota A. Tetrahedron Lett. 2003; 44: 1659
• 1e Beutler JA, Brubaker AN. Drugs Future 1987; 12: 957
• 1f Brown DG, Bernstein PR, Wu Y, Urbanek RA, Becker CW, Throner SR, Dembofsky BT, Steelman GB, Lazor LA, Scott CW, Wood MW, Wesolowski SS, Nugiel DA, Koch S, Yu J, Pivonka DE, Li S, Thompson C, Zacco A, Elmore CS, Schroeder P, Liu J.-W, Hurley CA, Ward S, Hunt HJ, Williams K, McLaughlin J, Hoesch V, Sydserff S, Maier D, Aharony D. ACS Med. Chem. Lett. 2013; 4: 46

Selected recent reports on the synthesis of pyrrole and azepine derivatives:
• 2a Evans PA, Inglesby PA. J. Am. Chem. Soc. 2012; 134: 3635
• 2b Jiang H, He J, Liu T, Yu J.-Q. J. Am. Chem. Soc. 2016; 138: 2055
• 2c Liu R, Winston-Mcpherson GN, Yang Z.-Y, Zhou X, Song W, Guzei IA, Xu X, Tang W. J. Am. Chem. Soc. 2013; 135: 8201
• 2d Shaw MH, Melikhova EY, Kloer DP, Whittingham WG, Bower JF. J. Am. Chem. Soc. 2013; 135: 4992
• 2e Shaw MH, McCreanor NG, Whittingham WG, Bower JF. J. Am. Chem. Soc. 2015; 137: 463
• 2f Nicolle SM, Lewis W, Hayes CJ, Moody C. J. Angew. Chem. Int. Ed. 2016; 55: 3749
• 2g Liu K, Zhu C, Min J, Peng S, Xu G, Sun J. Angew. Chem. Int. Ed. 2015; 54: 12962
• 2h Knight JG, Tchabanenko K, Stoker PA, Harwood SJ. Tetrahedron Lett. 2005; 46: 6261
• 2i Ohmatsu K, Imagawa N, Ooi T. Nat. Chem. 2014; 6: 47

Azepines:
• 2j Yang J.-M, Zhu C.-Z, Tang X.-Y, Shi M. Angew. Chem. Int. Ed. 2014; 53: 5142
• 2k Nakamura I, Okamoto M, Sato Y, Terada M. Angew. Chem. Int. Ed. 2012; 51: 10816
• 2l Zhou M.-B, Song R.-J, Wang C.-Y, Li J.-H. Angew. Chem. Int. Ed. 2013; 52: 10805
• 2m Yang Y, Zhou M.-B, Ouyang X.-H, Pi R, Song R.-J, Li J.-H. Angew. Chem. Int. Ed. 2015; 54: 6595
• 2n Wender PA, Pedersen TM, Scanio MJ. C. J. Am. Chem. Soc. 2002; 124: 15154
• 2o Shi Z, Grohmann C, Glorius F. Angew. Chem. Int. Ed. 2013; 52: 5393
• 2p Li T, Xu F, Li X, Wang C, Wan B. Angew. Chem. Int. Ed. 2016; 55: 2861

For reviews, see:
• 2q Nakamura I, Yamamoto Y. Chem. Rev. 2004; 104: 2127
• 2r Han M.-Y, Jia J.-Y, Wang W. Tetrahedron Lett. 2014; 55: 784
• 3 Feng J-J, Zhang J. ACS Catal. 2016; 6: 6651
• 4 Kinderman SS, van Maarseveen JH, Schoemaker HE, Hiemstra H, Rutjes FP. J. T. Org. Lett. 2001; 3: 2045
• 5 Feldman KS, Bruendl MM, Schildknegt K, Bohnstedt AC. J. Org. Chem. 1996; 61: 5440
• 6a Jacoby D, Celerier JP, Haviari G, Petit H, Lhommet G. Synthesis 1992; 884
• 6b Zhu W, Cai G, Ma D. Org. Lett. 2005; 7: 5545
• 7a Wolf LB, Tjen KC. M. F, Rutjes FP. J. T, Hiemstra H, Schoemaker HE. Tetrahedron Lett. 1998; 39: 5081
• 7b Busacca CA, Dong Y. Tetrahedron Lett. 1996; 37: 3947
• 7c Yin Y, Ma W, Chai Z, Zhao G. J. Org. Chem. 2007; 72: 5731
• 7d Ma S, Yu F, Li J, Gao W. Chem. Eur. J. 2007; 13: 247
• 8 Zhou X, Zhang H, Yuan J, Mai L, Li Y. Tetrahedron Lett. 2007; 48: 7236
• 9a Ding C.-H, Dai L.-X, Hou X.-L. Tetrahedron 2005; 61: 9586
• 9b Knight DW, Redfern AL, Gilmore J. J. Chem. Soc., Perkin Trans. 1 2002; 622
• 10 Sonesson C, Hallberg A. Tetrahedron Lett. 1995; 36: 4505
• 11a Saegusa T, Ito Y, Kinoshita H, Tomita S. J. Org. Chem. 1971; 36: 3316
• 11b Schöllkopf U, Hantke K. Liebigs Ann. Chem. 1973; 1571
• 11c Guo C, Xue M.-X, Zhu M.-K, Gong L.-Z. Angew. Chem. Int. Ed. 2008; 47: 3414
• 12 Wurz RP, Charette AB. Org. Lett. 2005; 7: 2313
• 13 Strand D, Wender PA. J. Am. Chem. Soc. 2009; 131: 7528
• 14 Sun H, Yang C, Lin R, Xia W. Adv. Synth. Catal. 2014; 356: 2775
• 15a Kapoor R, Tripathi S, Singh SN, Keshari T, Yadav LD. S. Tetrahedron Lett. 2017; 58: 3814
• 15b Kapoor R, Chawla R, Yadav LD. S. Tetrahedron Lett. 2019; 60: 805
• 15c Chawla R, Yadav LD. S. Org. Biomol. Chem. 2019; 17: 4761
• 15d Kapoor R, Chawla R, Yadav LD. S. Tetrahedron Lett. 2020; 61: 152505
• 16 Ye Q, Xu X, Cheng D, Guan B, Ye H, Li X. ARKIVOC 2017; (v): 314
• 17 Fukuyama T, Jow C.-K, Cheung M. Tetrahedron Lett. 1995; 36: 6373
• 18 General Procedure for the Synthesis of 2,3-Dihydropyrroles 3 To a stirred solution of aziridine (1 mmol) and alkyne (2 mmol) in isopropyl alcohol (3 mL) was added PhN₂BF₄ (1.5 equiv) and Ru(bpy)₃(BF₄)₂ photocatalyst (2 mol%) at room temperature under visible-light irradiation (blue LED, 3 W, λ = 427 nm). The reaction typically turned yellow or orange/brownish as the reaction progressed. Upon complete consumption of aziridine (TLC control), the reaction was added onto a short SiO₂ flash column (flushed with Et₃N (5%) doped eluent) or an Al₂O₃ (neutral) flash column and eluted with 6.25% ethyl acetate in petroleum ether. Product-containing fractions were concentrated under reduced pressure to leave the corresponding dihydropyrroles 3. Characterization Data of Representative Compounds 3 3,5-Diphenyl-1-tosyl-2,3-dihydro-1H-pyrrole (3a) ¹H NMR (400 MHz, CDCl₃): δ = 7.70–7.65 (m, 2 H), 7.60–7.50 (m, 2 H), 7.49–7.44 (m, 3 H), 7.26–7.21 (m, 2 H), 7.19–7.14 (m, 3 H), 6.79–6.74 (m, 2 H), 5.32 (d, J = 2.4 Hz, 1 H), 4.40 (dd, J = 11.9, 8.7 Hz, 1 H), 3.83 (dd, J = 11.9, 9.4 Hz, 1 H), 3.61 (ddd, J = 10.0, 8.0, 2.3 Hz, 1 H), 2.45 (s, 3 H).¹³C NMR (100 MHz, CDCl₃): δ = 144.9, 142.9, 141.4, 133.4, 132.6, 129.6, 128.9, 128.5, 128.01, 128.0, 127.6, 127.1, 125.9, 120.0, 59.6, 46.9, 21.9. HRMS (ESI): m/z calcd for [C₂₃H₂₁NO₂S + Na⁺]: 398.1191; found: 398.1196. 3-(4-Bromophenyl)-5-phenyl-1-tosyl-2,3-dihydro-1H-pyrrole (3f) ¹H NMR (400 MHz, CDCl₃): δ = 7.69–7.66 (m, 2 H), 7.42–7.30 (m, 5 H), 7.29–7.21 (m, 2 H), 7.29–7.20 (m, 2 H), 6.76–6.65 (m, 2 H), 5.39 (d, J = 2.8 Hz, 1 H), 4.28 (dd, J = 12.6, 9.9 Hz, 1 H), 3.82 (dd, J = 12.6, 7.3 Hz, 1 H), 3.69 (ddd, J = 9.9, 7.2, 2.7 Hz, 1 H), 2.32 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 146.4, 144.0, 142.6, 133.9, 132.6, 131.9, 129.2, 130.1, 129.0, 128.6, 128.0, 127.3, 120.9, 118.1, 59.9, 45.2, 21.6. HRMS (ESI): m/z calcd for [C₂₃H₂₀NO₂SBr + Na⁺]: 476.0296; found: 476.0290. 3-Methyl-3,5-diphenyl-1-tosyl-2,3-dihydro-1H-pyrrole (3k) ¹H NMR (400 MHz, CDCl₃): δ = 7.63–7.56 (m, 2 H), 7.42–7.35 (m, 3 H), 7.33–7.28 (m, 2 H), 7.16–7.08 (m, 3 H), 7.04 (dd, J = 8.0, 0.5 Hz, 2 H), 6.98–6.92 (m, 2 H), 5.40 (s, 1 H), 4.16 (d, J = 12.3 Hz, 1 H), 4.05 (d, J = 12.2 Hz, 1 H), 2.34 (s, 3 H), 2.24 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 147.6, 143.7, 143.5, 133.2, 132.7, 129.2, 128.8, 128.4, 128.3, 127.8, 127.7, 125.9, 125.5, 123.7, 65.6, 48.2, 29.0, 21.5. HRMS (ESI): m/z calcd for [C₂₄H₂₃NO₂S + Na⁺]: 412.1347; found: 412.1345.