Synlett 2014; 25(3): 428-432
DOI: 10.1055/s-0033-1340460
letter
© Georg Thieme Verlag Stuttgart · New York

Advancing the Reactivity of Dimethylcyclopropane-1,1-dicarboxylates via Cross Metathesis

Matt R. Vriesen
Department of Chemistry, The University of Western Ontario, London, ON, N6A 5B7, Canada   Fax: +1(519)6613022   Email: makerr@uwo.ca
,
Huck K. Grover
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: 21 October 2013

Accepted after revision: 19 November 2013

Publication Date:
10 December 2013 (online)


Abstract

Cross metathesis of the readily available dimethyl 2-vinylcycloropane-1,1-dicarboxylate with a variety of olefins gave divergent access to new donor–acceptor cyclopropanes bearing a π-donor alkenyl substituent. The synthetic utility of these cyclopropanes was shown by their participation in cycloaddition reactions with nitrones to yield the anticipated tetrahydro-1,2-oxazines. Hydrogenation yielded the alkyl-substituted adducts which would be more difficult to access via other means.

Supporting Information

 
  • References and Notes


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  • 15 Product 9d was isolated as an inseparable mixture with starting cyclopropane.
  • 16 General Experimental Procedure for the Synthesis of Substituted Vinyl Cyclopropane 6a–k: Dimethyl 2-vinylcyclopropane-1,1-dicarboxylate (5; 1 equiv) and olefin (1.4–5.0 equiv) were dissolved in anhyd CH2Cl2. Grubbs 2nd generation catalyst (G2; 0.01 equiv) was then added and a reflux condenser was attached. The reaction vessel was then purged with argon and the reaction was brought to reflux. Upon completion by TLC analysis the solvent was removed and the residue was purified by flash chromatography (EtOAc–hexanes) to yield the desired cyclopropanes 6ak. Analytical Data for Selected Compounds: Dimethyl 2-(Hex-1-enyl)cyclopropane-1,1-dicarboxylate (6a): 1H NMR (400 MHz, CDCl3): δ = 5.71 (dt, J = 15.3, 7.0 Hz, 1 H), 5.35 (ddt, J = 15.2, 8.2, 1.2 Hz, 1 H), 3.72 (s, 6 H), 2.54 (q, J = 8.2 Hz, 1 H), 1.99 (q, J = 7.0 Hz, 2 H), 1.68 (dd, J = 7.4, 4.7 Hz, 1 H), 1.55 (dd, J = 9.4, 4.7 Hz, 1 H), 1.25–1.31 (m, 4 H), 0.86 (t, J = 7.4 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 170.2, 168.0, 135.6, 124.2, 52.6, 35.6, 32.1, 31.2, 27.5, 27.0, 22.0, 20.8, 13.9. IR (thin film): 3000, 2955, 2929, 2857, 1730, 1437, 1332, 1280, 1260, 1210, 1131 cm–1. HRMS: m/z calcd for C13H20O4: 240.1362; found: 240.1368 (6:1 trans to cis). Dimethyl 2-Styrylcyclopropane-1,1-dicarboxylate (6f): 1H NMR (400 MHz, CDCl3): δ = 7.28–7.32 (m, 4 H), 7.20–7.26 (m, 1 H), 6.65 (d, J = 16.0 Hz, 1 H), 5.81 (dd, J = 16.0, 9.0 Hz, 1 H), 3.77 (s, 3 H), 3.73 (s, 3 H), 2.76 (q, J = 8.2 Hz, 1 H), 1.85 (dd, J = 7.8, 5.1 Hz, 1 H), 1.70 (dd, J = 9.0, 5.1 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 169.9, 167.9, 136.7, 133.9, 128.6, 127.6, 126.1, 124.5, 52.8, 52.7, 36.0, 31.7, 21.3. IR (thin film): 3027, 2953, 2847, 1731, 1494, 1437, 1283, 1252, 1207, 1128, 964, 770, 744, 694 cm–1. HRMS: m/z calcd for C15H16O4: 260.1049; found: 260.1049 (only E-olefin observed by 1H NMR). Dimethyl 2-(3-Oxobut-1-enyl)cyclopropane-1,1-dicarboxylate (6j): 1H NMR (600 MHz, CDCl3): δ = 6.23–6.30 (m, 2 H), 3.71 (s, 6 H), 2.56–2.65 (m, 1 H), 2.15 (s, 3 H), 1.78 (dd, J = 7.6, 5.3 Hz, 1 H), 1.72 (dd, J = 8.8, 4.7 Hz, 1 H). 13C NMR (150 MHz, CDCl3): δ = 197.0, 169.0, 167.2, 142.1, 133.3, 52.9, 52.8, 36.5, 29.8, 27.0, 21.5. IR (thin film): 3007, 2956, 2856, 1731, 1674, 1625, 1438, 1333, 1291, 1253, 1212, 1131, 983 cm–1. HRMS: m/z calcd for C11H14O5: 226.0841; found: 226.0831 (only E-olefin observed by 1H NMR). General Experimental Procedure for the Synthesis of Tetrahydro-1,2-oxazines 9ad: Yb(OTf)3·xH2O (5–20 mol %) was added to a solution of cyclopropane 6a, 6f, and 7a,b (1 equiv) and nitrone 8 (1.2 equiv) in CH2Cl2 or 1,2-dichloroethane. Reactions in CH2Cl2 were performed at r.t., while reactions in 1,2-dichloroethane were refluxed for 18 h. The reaction mixture was wet loaded and purified by flash chromatography (EtOAc–hexanes) to yield the desired tetrahydro-1,2-oxazine 9ad. Analytical Data for Selected Compounds: Dimethyl 6-(Hex-1-enyl)-2-phenyl-3-p-tolylmorpholine-4,4-dicarboxylate (9a): 1H NMR (600 MHz, CDCl3): δ = 7.49–7.56 (m, 2 H), 7.14–7.21 (m, 3 H), 6.91–6.98 (m, 4 H), 5.88–5.97 (m, 1 H), 5.64–5.76 (m, 1 H), 5.62 (s, 1 H), 4.40–4.47 (m, 1 H), 3.88 (s, 3 H), 3.45 (s, 3 H), 2.44–2.61 (m, 2 H), 2.05–2.11 (m, 5 H), 1.33–1.49 (m, 4 H), 0.95 (t, J = 7.4 Hz, 3 H). 13C NMR (150 MHz, CDCl3): δ = 170.1, 168.4, 146.3, 135.2, 135.0, 130.8, 130.5, 129.0, 127.9, 127.8, 127.7, 116.0, 77.2, 65.9, 59.2, 53.3, 52.5, 32.2, 30.8, 22.3, 22.2, 20.5, 13.9. IR (thin film): 3028, 2954, 2927, 2859, 1742, 1509, 1453, 1434, 1235, 1177, 1149, 1082, 967, 821, 755, 702 cm–1. HRMS: m/z calcd for C27H33NO5: 451.2359; found: 451.2354. (6:1 trans to cis). General Experimental Procedure for Olefin Reduction to Tetrahydro-1,2-oxazines 9cd: Vinyl tetrahydro-1,2-oxazines 9a and 9b (1 equiv) were dissolved in THF–H2O (1:1). Tosylhydrazine (10 equiv) and NaOAc (13 equiv) were added and the reaction mixture was heated to reflux for 24 h. H2O was added to the reaction and the aqueous layer was extracted with Et2O (4 ×). The organic phases were combined and dried with MgSO4, filtered, and the solvent was removed. The residue was purified by flash chromatography (EtOAc–hexanes) to yield the desired tetrahydro-1,2-oxazines (9c and 9d). Analytical Data for Selected Compounds: Dimethyl 6-Phenethyl-2-phenyl-3-p-tolylmorpholine-4,4-dicarboxylate (9d): 1H NMR (600 MHz, CDCl3): δ = 7.52–7.56 (m, 2 H), 7.30–7.34 (m, 2 H), 7.26–7.29 (m, 2 H), 7.17–7.24 (m, 4 H), 6.94–7.00 (m, 4 H), 5.67 (s, 1 H), 3.98–4.07 (m, 1 H), 3.85 (s, 3 H), 3.46 (s, 3 H), 2.96–3.04 (m, 1 H), 2.83–2.91 (m, 1 H), 2.46–2.52 (m, 2 H), 2.13–2.23 (m, 4 H), 1.97–2.06 (m, 1 H). 13C NMR (150 MHz, CDCl3): δ = 170.2, 168.5, 146.4, 141.6, 135.2, 130.7, 130.5, 129.1, 128.4, 128.0, 127.9, 126.0, 115.7, 76.5, 66.0, 59.2, 53.3, 52.5, 36.4, 31.9, 31.0, 20.6 (one carbon missing presumably due to overlap in the aromatic region). IR (thin film): 3027, 2951, 2924, 2857, 1741, 1509, 1453, 1434, 1236, 1166, 1090, 820, 753, 701 cm–1. HRMS: m/z calcd for C29H31NO5: 473.2202; found: 473.2191.