Synlett 2014; 25(16): 2297-2300
DOI: 10.1055/s-0034-1379107
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© Georg Thieme Verlag Stuttgart · New York

Catalyst-Free Tandem Ring-Opening/Click Reaction of Acetylene-Bearing Donor–Acceptor Cyclopropanes

Michelle E. Flisar
Department of Chemistry, The University of Western Ontario, London, ON, N6A 5B7, Canada   Fax: +1(519)6613022   Email: makerr@uwo.ca
,
Michael R. Emmett
Department of Chemistry, The University of Western Ontario, London, ON, N6A 5B7, Canada   Fax: +1(519)6613022   Email: makerr@uwo.ca
,
Michael A. Kerr*
Department of Chemistry, The University of Western Ontario, London, ON, N6A 5B7, Canada   Fax: +1(519)6613022   Email: makerr@uwo.ca
› Author Affiliations
Further Information

Publication History

Received: 18 July 2014

Accepted after revision: 21 August 2014

Publication Date:
08 September 2014 (online)

Abstract

Cyclopropane-1,1-hemimalonates bearing a 2-(2-alkynylphenyl) moiety underwent ring opening by an azide nucleophile, generating an alkyl azide that, in turn, underwent [3+2]-dipolar cycloaddition with the alkyne. The products are novel linearly fused tricyclic 1,2,3-triazoles.

Supporting Information

 
  • References and Notes


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  • 11 Synthesis of Triazoles 8ah; General Procedure: Cyclopropane hemimalonate 18ah (1 equiv) was dissolved in a solution of 2-methoxyethanol–H2O (10:1) and then NaN3 (1.2 equiv) and NH4Cl (1.4 equiv) were added. The mixture was heated to reflux and the reaction was monitored by TLC analysis until completion (1.5–2 h). The reaction mixture was then cooled to room temperature, and H2O was added. The reaction was extracted three times with Et2O. The organic layers were combined and dried with MgSO4, filtered, and the solvent was removed. The residue was purified by flash column chromatography (EtOAc–hexanes) to yield the desired triazole 8ah.Methyl 3-(8H-[1,2,3]Triazolo[5,1-a]isoindol-8-yl)-propanoate (8a): Synthesized from 2-(2-ethynylphenyl)-1-(methoxycarbonyl)cyclopropanecarboxylic acid (18a; 0.080 g, 0.328 mmol), NaN3 (0.026 g, 0.394 mmol), NH4Cl (0.025 g, 0.459 mmol), 2-methoxyethanol–H2O. Yield: 0.064 g (0.263 mmol, 80%); clear oil; Rf = 0.12 (EtOAc–hexanes, 30%). IR (thin film): 3136, 3057, 2998, 2951, 2850, 1734, 1624, 1471, 1437, 1416, 1379, 1245, 1205, 1094 cm–1. 1H NMR (600 MHz, CDCl3): δ = 7.82 (s, 1 H), 7.63 (d, J = 7.0 Hz, 1 H), 7.50–7.40 (m, 3 H), 5.54 (dd, J = 7.8, 3.9 Hz, 1 H), 3.64 (s, 3 H), 2.81–2.73 (m, 1 H), 2.60–2.52 (m, 1 H), 2.47–2.40 (m, 1 H), 2.29–2.20 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ = 172.8, 144.8, 129.1, 128.6, 127.1, 124.3, 123.8, 121.7, 61.9, 51.8, 28.8, 28.5. HRMS (EI): m/z calcd for C13H13N3O2: 243.1008; found: 243.1006.