Copper-Catalyzed Ring Expansion of Vinyl Aziridines under Mild Conditions

In expression of our respect to Professor Barry M. Trost on the occasion of his 80^th birthday.

Abstract

Vinyl aziridines are versatile starting materials toward ring-expansion transformations. Such processes are widely used to give various medium or larger N-heterocycles of synthetic interest. This letter describes a copper-catalyzed ring expansion of vinyl aziridines to 3-pyrrolines by using a Cu(I) salt [(CuOTf)₂·toluene or Cu(MeCN)₄·PF₆]. In particular, this transformation occurs under mild conditions (THF, rt).

Key words

ring expansion - vinyl aziridines - pyrrolines - copper catalysis - heterocycles

Publication History

Received: 29 October 2020

Accepted after revision: 08 December 2020

Article published online:
05 January 2021

• References and Notes


For selected reviews, see:
• 1a Donald JR, Unsworth WP. Chem. Eur. J. 2017; 23: 8780
• 1b Clarke AK, Unsworth WP. Chem. Sci. 2020; 11: 2876
• 1c Mack DJ, Njardarson JT. ACS Catal. 2013; 3: 272
• 1d Huang C.-Y, Doyle AG. Chem. Rev. 2014; 114: 8153
• 1e Dauban P, Malik G. Angew. Chem. Int. Ed. 2009; 48: 9026
• 2 For a review, see: Ohno H. Chem. Rev. 2014; 114: 7784

For some selected recent publications see:
• 3a Kaldas SJ, Kran E, Mück-Lichtenfeld C, Yudin AK, Studer A. Chem. Eur. J. 2020; 26: 1501
• 3b Zhao Q.-Q, Zhou X.-S, Xu S.-H, Wu Y.-L, Xiao W.-J, Chen J.-R. Org. Lett. 2020; 22: 2470
• 3c Wan S.-H, Liu S.-T. Tetrahedron 2019; 75: 1166
• 3d Singh D, Ha H.-J. Org. Biomol. Chem. 2019; 17: 3093
• 3e Wu A, Feng Q, Sung HH. Y, Williams ID, Sun J. Angew. Chem. Int. Ed. 2019; 58: 6776
• 3f Zhu C.-Z, Feng J.-J, Zhang J. Chem. Commun. 2018; 54: 2401
• 3g Jiang F, Yuan F.-R, Jin L.-W, Mei G.-J, Shi F. ACS Catal. 2018; 8: 10234 ; and references cited therein
• 4a Spielmann K, Tosi E, Lebrun A, Niel G, van der Lee A, de Figueiredo RM, Campagne J.-M. Tetrahedron 2018; 74: 6497
• 4b Spielmann K, van der Lee A, de Figueiredo RM, Campagne J.-M. Org. Lett. 2018; 20: 1444
• 5a Taylor RD, MacCoss M, Lawson AD. J. J. Med. Chem. 2014; 57: 5845
• 5b Vitaku E, Smith DT, Njardarson JT. J. Med. Chem. 2014; 57: 10257
• 5c Aldeghi M, Malhotra S, Selwood DL, Chan AW. E. Chem. Biol. Drug Des. 2014; 83: 450
• 6a Brichacek M, Lee D, Njardarson JT. Org. Lett. 2008; 10: 5023
• 6b Brichacek M, Villalobos MN, Plichta A, Njardarson JT. Org. Lett. 2011; 13: 1110
• 6c Mack DJ, Njardarson JT. Chem. Sci. 2012; 3: 3321
• 6d Batory LA, McInnis CE, Njardarson JT. J. Am. Chem. Soc. 2006; 128: 16054

For thermal rearrangements of 2-vinyl aziridines, see:
• 7a Mente PG, Heine HW. J. Org. Chem. 1971; 36: 3076
• 7b Pommelet JC, Chuche J. Can. J. Chem. 1976; 54: 1571
• 7c Borel D, Gelas-Mialhe Y, Vessière R. Can. J. Chem. 1976; 54: 1590
• 7d For a [4+1] access to 3-pyrrolines, see also: Wu Q, Hu J, Ren X, Zhou J. Chem. Eur. J. 2011; 17: 11553
• 8a Kobayashi Y, Taguchi T, Morikawa T, Tokuno E, Sekiguchi S. Chem. Pharm. Bull. 1980; 28: 262
• 8b Ferraris D, Young B, Cox C, Drury WJ. III, Dudding T, Leckta T. J. Org. Chem. 1998; 63: 6090
• 8c Pagenkopf BL, Krüger J, Stojanovic A, Carreira EM. Angew. Chem. Int. Ed. 1998; 37: 3124 ; See also the Njardarson mechanistic studies in reference 6 (c)
• 9 After a short screening of solvents (e.g., THF, CH₂Cl₂, toluene, hexane), THF was chosen to perform the transformation.
• 10 Desmarchelier A, Pereira de Sant’Ana D, Terrasson V, Campagne J.-M, Moreau X, Greck C, de Figueiredo RM. Eur. J. Org. Chem. 2011; 4046
• 11 Terrasson V, van der Lee A, de Figueiredo RM, Campagne J.-M. Chem. Eur. J. 2010; 16: 7875
• 12 Bao X, Wang Q, Zhu J. Angew. Chem. Int. Ed. 2018; 57: 1995

For related reactions involving Pt- or Au-catalyzed ring expansions of alkynyl aziridines, see:
• 13a Yoshida M, Easmin S, Al-Amin M, Hirai Y, Shishido K. Tetrahedron 2011; 67: 3194
• 13b Yoshida M, Maeyama Y, Al-Amin M, Hirai Y, Shishido K. J. Org. Chem. 2011; 76: 5813
• 13c Davies PW, Martin N. Org. Lett. 2009; 11: 2293
• 13d Chen D.-D, Hou X.-L, Dai L.-X. Tetrahedron Lett. 2009; 50: 6944
• 14 4-Benzyl-2-methyl-1-tosyl-2,5-dihydro-1H-pyrrole (6a): Typical Procedure A flame-dried 10 mL flask equipped with a stirrer bar was charged with vinyl aziridine 1a (46 mg, 0.14 mmol, 1.00 equiv), (CuOTf)₂·toluene (3.5 mg, 0.007 mmol, 0.05 equiv), and THF (0.7 mL), and the mixture was stirred for 2 h under argon at rt. The solvent evaporated under reduced pressure, and the crude product was purified by chromatography [silica gel, pentane–EtOAc (100:0 to 70:30)] to give a pale-yellow solid; yield: 28 mg (60%); mp 80–83 °C. FTIR (neat): 1402, 1355, 1178, 1163, 1090, 993, 945, 858, 840, 765, 664 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.65–7.63 (m, 2 H), 7.27–7.20 (m, 5 H), 7.01–6.99 (m, 2 H), 5.19–5.17 (m, 1 H), 4.48–4.46 (m, 1 H), 4.04–3.90 (m, 2 H), 3.33–3.23 (m, 2 H), 2.43 (s, 3 H), 1.38 (d, J = 6.40 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 143.2, 137.6, 137.1, 134.8, 129.6 (2 C), 128.5 (2 C), 128.5 (2 C), 127.4 (2 C), 126.5, 126.3, 63.4, 56.6, 35.1, 22.9, 21.5. HRMS-ASAP: m/z [M + H]⁺ calcd for C₁₉H₂₂NO₂S: 328.1371; found: 328.1381.