Synlett 2016; 27(05): 745-748
DOI: 10.1055/s-0035-1560555
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© Georg Thieme Verlag Stuttgart · New York

Facile Preparation of Functionalized 1-Substituted Cycloalkenes via an Iodine Atom Transfer Radical Addition–Elimination Process

Daniel Meyer
University of Bern, Department of Chemistry and Biochemistry, Freiestrasse 3, 3012 Bern, Switzerland   Email: philippe.renaud@dcb.unibe.ch
,
Estelle Vin
University of Bern, Department of Chemistry and Biochemistry, Freiestrasse 3, 3012 Bern, Switzerland   Email: philippe.renaud@dcb.unibe.ch
,
Benjamin Wyler
University of Bern, Department of Chemistry and Biochemistry, Freiestrasse 3, 3012 Bern, Switzerland   Email: philippe.renaud@dcb.unibe.ch
,
Guillaume Lapointe
University of Bern, Department of Chemistry and Biochemistry, Freiestrasse 3, 3012 Bern, Switzerland   Email: philippe.renaud@dcb.unibe.ch
,
Philippe Renaud*
University of Bern, Department of Chemistry and Biochemistry, Freiestrasse 3, 3012 Bern, Switzerland   Email: philippe.renaud@dcb.unibe.ch
› Author Affiliations
Further Information

Publication History

Received: 23 October 2015

Accepted after revision: 16 November 2015

Publication Date:
23 December 2015 (online)

Abstract

An efficient and scalable two-step one-pot procedure for the preparation of cycloalkenes substituted with a functionalized alkyl side chain is reported. This method is based on a triethylborane-mediated iodine atom transfer radical addition (ATRA) of 1-iodoesters and related compounds to methylenecycloalkanes followed by treatment of the intermediate tertiary iodide with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to promote a selective endo elimination.

Supporting Information

 
  • References and Notes

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  • 11 General Procedure for Iodine ATRA–Elimination Reaction A solution of Et3B (0.5 mL, 1.0 M in EtOH, 0.5 mmol) was added over 2 h by syringe pump to a stirred mixture of the iodide 2, 4, or 5 (2.0 mmol) and olefin 1 (1 mmol) in EtOH–H2O (1:1, 10 mL) in the dark and open to air. After complete addition, the brown mixture was allowed to stir for 1 h at r.t. DBU (457 mg, 3 mmol) was added at 0 °C, and the mixture was stirred at r.t. overnight. After addition of a sat. aq solution of NH4Cl (50 mL), the mixture was extracted with Et2O (20 and 10 mL), and the organic phases were washed with brine (10 mL). The combined organic layers were dried over Na2SO4 and concentrated. The crude product was purified by column chromatography. Ethyl 3-{1,2,3,6-Tetrahydro-[1,1′-biphenyl]-4-yl}propanoate (3e) Colorless and clear oil; 76% yield; endo/exo = 94:6. 1H NMR (300 MHz, CDCl3): δ = 7.34–7.15 (m, 5 H), 5.54–5.48 (m, 1 H), 4.14 (q, J = 7.1 Hz, 2 H), 2.80–2.67 (m, 1 H), 2.47–2.40 (m, 2 H), 2.35–2.21 (m, 3 H), 2.20–1.91 (m, 4 H), 1.82–1.68 (m, 1 H), 1.26 (t, J = 7.1 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 173.5, 147.1, 136.1, 128.3 (2 C), 126.9, 126.8, 126.0, 121.2, 60.3, 40.1, 33.4, 32.9, 32.6, 30.0, 28.9, 14.3. IR (neat): 3043, 2915, 2087, 1731, 1602, 1493, 1160, 916. HRMS (ESI-TOF): m/z calcd for C17H23O2 [M + H]+: 259.1693; found: 259.1691. 3-{1,2,3,6-Tetrahydro-[1,1′-biphenyl]-4-yl}propanenitrile (6e) Colorless and clear oil; 70% yield; endo/exo = 94:6. 1H NMR (300 MHz, CDCl3): δ = 7.32–7.26 (m, 2 H), 7.25–7.16 (m, 3 H), 5.67–5.61 (m, 1 H), 2.83–2.70 (m, 1 H), 2.51–2.47 (m, 2 H), 2.40–2.27 (m, 3 H), 2.26–2.10 (m, 2 H), 2.08–1.93 (m, 2 H), 1.85–1.71 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ = 146.6, 133.9, 128.4 (2 C), 126.9 (2 C), 126.1, 123.6, 119.6, 39.8, 33.3, 33.0, 29.8, 28.5, 16.1. IR (neat): 3025, 2919, 2836, 2248, 1602, 1494, 1436, 908, 729, 699. HRMS (ESI-TOF): m/z calcd for C15H18N [M + H]+: 212.1434; found: 212.1427. 4-[2-(Phenylsulfonyl)ethyl]-1,2,3,6-tetrahydro-1,1′-biphenyl (7e) Amorphous white solid; 68% yield; endo/exo >98:2; mp 80–82 °C. 1H NMR (300 MHz, CDCl3): δ = 8.01–7.88 (m, 2 H), 7.72–7.52 (m, 3 H), 7.32–7.26 (m, 2 H), 7.32–7.25 (m, 3 H), 5.53–5.46 (m, 1 H), 3.28–3.18 (m, 2 H), 2.72–2.58 (m, 1 H), 2.46–2.37 (m, 2 H), 2.28–2.16 (m, 1 H), 2.15–2.00 (m, 2 H), 1.99–1.85 (m, 2 H), 1.75–1.57 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ = 146.6, 139.3, 133.7, 133.4, 129.3, 128.4, 128.1, 126.8, 126.1, 123.2, 54.8, 39.7, 33.3, 30.3, 29.7, 28.8. IR (neat): 2939, 2892, 2831, 1495, 1446, 1305, 1283, 1147, 1139, 1121, 1088, 887. HRMS (ESI-TOF): m/z calcd for C20H23O2S [M + H]+: 327.1413; found: 327.1404.
  • 12 Scale-up Experiment for Ethyl 3-(Cyclohex-1-en-1-yl)propanoate (3a) A solution of Et3B (30 mL, 1.0 M in EtOH, 30 mmol) was added over 2 h by syringe pump to a stirred solution of ethyl 2-iodoacetate (2, 25.68 g, 120 mmol) and methylenecyclohexane (1a, 5.77 g, 60 mmol) in EtOH–H2O (3:1, 60 mL) in the dark and open to air. After complete addition, the brown mixture was allowed to stir for 2 h at r.t. DBU (27.40 g, 180 mmol) was added at <10 °C, and the mixture was stirred at r.t. overnight. After addition of a sat. aq solution of NH4Cl (150 mL), the mixture was extracted with pentane (150 and 75 mL), and the organic phases were washed with H2O (75 mL), dried over Na2SO4, and concentrated. The crude product was purified by column chromatography (Et2O–pentane, 5:95) to provide 3a (8.06 g, 74%) as a colorless and clear oil. 1H NMR (300 MHz, CDCl3): δ = 5.45–5.37 (m, 1 H), 4.12 (q, J = 7.1 Hz, 2 H), 2.45–2.33 (m, 2 H), 2.25 (t, J = 7.7 Hz, 2 H), 2.02–1.87 (m, 4 H), 1.67–1.47 (m, 4 H), 1.25 (t, J = 7.1 Hz, 3 H). 13C NMR (75 MHz, CDCl3): δ = 173.6, 136.1, 121.6, 60.2, 33.1, 33.0, 28.3, 25.2, 22.9, 22.4, 14.3. IR (neat): 2925, 1733, 1445, 1368, 1340, 1288, 1248, 1157, 1081, 1038, 919, 856, 838 cm–1. HRMS (ESI-TOF): m/z calcd for C11H18O2Na [M + Na]+: 205.1199; found: 205.1193.
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