Download PDF
Synlett 2005(6): 0915-0918  
DOI: 10.1055/s-2005-864827
LETTER
© Georg Thieme Verlag Stuttgart · New York

Radical Cyclizations as Key Step for the Stereoselective Synthesis of Bi- and Tricyclic Sesquiterpene Lactones

Eva Jezek, Andreas Schall, Peter Kreitmeier, Oliver Reiser*
Institut für Organische Chemie der Universität Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany
Fax: +49(941)9434121; e-Mail: Oliver.Reiser@chemie.uni-regensburg.de;
Further Information

Publication History

Received 14 January 2005
Publication Date:
23 March 2005 (online)

    Permissions and Reprints All articles of this category

Abstract

A strategy towards the stereoselective synthesis of bi- and tricyclic sesquiterpene lactones is reported. As key step radical cyclizations of appropriately functionalized trans-4,5-disubstituted γ-butyrolactones, which are readily available from methyl 2-furoate, were carried out to give rise to 5,6-, 5,7- and 5,7,5-ring systems in diastereo- and enantiomerically pure form.

Key words

radical reactions - radicals - natural products - cyclizations - lactones

6

Selected Data:
Compound 8b: R f = 0.07 (SiO2, hexanes-EtOAc, 1:1). [α]20 D -26.5 (c 1.49, CH2Cl2). 1H NMR (600 MHz, CDCl3): δ = 2.62 (ddd, J = 15.1, 5.8, 1.1 Hz, 1 H), 2.70 (ddd, J = 15.1, 7.7, 1.1 Hz, 1 H), 2.80 (dd, J = 18.0, 9.9 Hz, 1 H), 2.92 (dd, J = 18.0, 7.7 Hz, 1 H), 3.22 (dddd, J = 9.9, 7.7, 6.3, 1.3 Hz, 1 H), 4.10 (m, 2 H), 4.91 (ddd, J = 7.6, 5.8, 6.2 Hz, 1 H), 5.15 (m, 1 H), 5.34 (m, 1 H), 9.75 (d, J = 1.3 Hz, 1 H). 13C NMR (151 MHz, CDCl3): δ = 28.77, 38.59, 48.15, 51.85, 76.86, 119.07, 139.59, 173.72, 197.15. IR (film): ν = 3078, 2939, 2735, 1779, 1727, 1651 cm-1. MS (CI-MS): m/z (%) = 220.1 (100) [M + NH4 +], 187.1 (2.45) [M + NH4 + - Cl]. HRMS: m/z calcd for C9H11O3Cl: 202.03967; found: 202.03939.
Compound 15: R f = 0.59 (SiO2, hexanes-EtOAc, 5:1). [α]20 D -21.52 (c 1.2, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 1.31 (t, J = 7.1 Hz, 3 H), 1.40 (m, 1 H), 1.80 (m, 1 H), 1.94 (m, 1 H), 2.17 (m, 1 H), 2.52 (m, 1 H), 2.62 (dd, J = 16.9, 12.8 Hz, 1 H), 2.83 (dd, J = 16.9, 8.0 Hz, 1 H), 3.0 (m, 1 H), 3.19 (m, 1 H), 3.97 (dt, J = 10.6, 3.6 Hz, 1 H), 4.21 (q, J = 7.1 Hz, 2 H), 6.91 (m, 1 H). 13C NMR (101 MHz, CDCl3): δ = 14.22, 23.21, 26.55, 35.50, 35.96, 43.21, 61.11, 81.13, 138.63, 139.34, 166.71, 175.10. IR (KBr): ν = 2924, 2855, 1777, 1701 cm-1. MS (CI, NH3): m/z (%) = 242.1 (100) [M + NH4 +]. Anal. Calcd for C12H16O4 (224.25): C, 64.27; H, 7.19; found: C, 64.27; H 6.92.
Compound(cis)-18: R f = 0.38 (SiO2, hexanes-EtOAc, 3:1). 1H NMR (300 MHz, CDCl3): δ = 1.29 (t, J = 7.1 Hz, 3 H), 1.34-1.40 (m, 1 H), 1.60-1.67 (m, 2 H), 1.77-1.85 (m, 1 H), 1.91-1.98 (m, 1 H), 1.98-2.05 (m, 1 H), 2.21 (dddd, J = 10.1, 7.1, 7.2, 7.3 Hz, 1 H), 2.36-2.45 (m, 1 H), 2.47-2.56 (m, 2 H), 2.57-2.64 (m, 1 H), 2.82 (dd, J = 16.9, 8.3 Hz, 1 H), 3.19-3.27 (m, 1 H), 4.13-4.25 (m, 3 H), 6.86-6.90 (m, 1 H). 13C NMR (76 MHz, CDCl3): δ = 12.24, 24.12, 30.11, 31.89, 35.51, 38.87, 41.39, 48.48, 61.18, 84.64, 134.99, 137.39, 167.19, 175.10. IR (film): ν = 2960, 2921, 2882, 1765, 1686, 1622 cm-1. MS (EI): m/z (%) = 264.1(100) [M+], 236.2 (22) [M - C2H4], 219.1 (40) [M - OC2H5], 218.1 (58) [M - EtOH]. HRMS: m/z calcd for C15H20O4: 264.13616; found: 264.13596.
Compound 21a: R f = 0.15 (SiO2, hexanes-EtOAc, 1:1). 1H NMR (400 MHz, CDCl3): δ = 1.26 (t, J = 7.1 Hz, 3 H), 1.83-1.86 (m, 2 H), 1.87-2.08 (ddddd, J = 6.5, 6.4, 3.9, 11.2, 11.1 Hz, 1 H), 2.26 (dd, J = 10.6, 12.1 Hz, 1 H), 2.27 (dd, J = 15.4, 6.5 Hz, 1 H), 2.27 (dd, J = 16.3, 13.2 Hz, 1 H), 2.33 (dd, J = 15.3, 6.3 Hz, 1 H), 2.47 (ddd, J = 13.5, 3.6, 1.1 Hz, 1 H), 2.52 (dd, J = 16.2, 6.4 Hz, 1 H), 2.87 (ddd, J = 12.0, 4.2, 0.8 Hz, 1 H), 3.81 (ddd, J = 12.0, 10.3, 4.2 Hz, 1 H), 4.13 (q, J = 7.1 Hz, 2 H), 4.87-4.93 (m, 2 H). 13C NMR (101 MHz, CDCl3): δ = 14.22, 34.08, 36.26, 39.09, 39.14, 40.52, 49.17, 60.74, 83.05, 114.60, 141.34, 171.64, 175.68. IR (film): ν = 3077, 2981, 2922, 1788, 1730, 1650 cm-1. MS (EI): m/z (%) = 238.3 (25) [M+], 220.3 (5) [M+ - H2O], 193.3 (64) [M+ - EtO], 192.3 (31) [M+ - EtOH], 164.3 (69) [M+ - EtOH, CO], 151.3 (71) [M+ - CH2CO2Et], 150.2 (72) [M+ - CH3CO2Et]. HRMS: m/z calcd for C13H18O4: 238.12050; found: 238.12018.
Compound 21b: R f = 0.24 (SiO2, hexanes-EtOAc, 1:1). [α]20 D -40.51 (c 0.40, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 1.67-1.82 (m, 2 H), 1.93-2.02 (m, 1 H), 2.09 (s, 3 H), 2.20 (ddd, J = 12.0, 10.6, 1.3 Hz, 1 H), 2.22 (dd, J = 16.3, 12.9 Hz, 1 H), 2.29-2.44 (m, 2 H), 2.34 (dd, J = 15.2, 6.6 Hz, 1 H), 2.44 (dd, J = 17.1, 5.6 Hz, 1 H), 2.80 (ddd, J = 12.0, 4.1, 0.5 Hz, 1 H), 3.77 (ddd, J = 12.0, 10.4, 4.3 Hz, 1 H), 4.82-4.86 (m, 2 H). 13C NMR (101 MHz, CDCl3): δ = 30.55, 34.32, 64.61, 39.14, 40.54, 47.88, 49.27, 83.06, 114.49. 141.44, 175.73, 206.56. IR (film): ν = 3080, 2977, 2950, 2918, 1780, 1710, 1632 cm-1. MS (PI-EI): m/z (%) = 208.1 (7) [M+ ], 151.1 (23) [M+ - CH2COMe], 150.1(44) [M+ - CH3COMe], 43.0(100) [COMe]. HRMS: m/z calcd for C12H16O3: 208.10995; found: 208.10961.
Compound 21c: R f = 0.21 (SiO2, hexanes-EtOAc, 1:1). [α]20 D -46.13 (c 0.74, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 1.87 (ddddd, J = 5.6, 11.8, 11.4, 6.1, 4.0 Hz, 1 H), 1.99 (dddd, J = 10.4, 13.2, 11.3, 6.5 Hz, 1 H), 2.04 (ddd, J = 13.4, 11.3, 1.4 Hz, 1 H), 2.32 (ddd, J = 12.1, 11.7, 1.4 Hz, 1 H), 2.35 (dd, J = 16.1, 13.1 Hz, 1 H), 2.40 (dd, J = 17.0, 6.3 Hz, 1 H), 2.45 (dd, J = 17.1, 5.6 Hz, 1 H), 2.57 (dd, J = 13.8, 3.7 Hz, 1 H), 2.70 (dd, J = 16.1, 6.3 Hz, 1 H), 2.91 (dd, J = 12.3, 4.1, 1 H), 3.84 (ddd, J = 12.0, 10.5, 4.2 Hz, 1 H), 4.97-5.01 (m, 2 H). 13C NMR (101 MHz, CDCl3): δ = 22.13, 33.1, 36.14, 38.76, 39.93, 48.23, 82.43, 115.65, 117.25, 140.02, 174.76. IR (film): ν = 3080, 2918, 2854, 2245, 1785, 1649 cm-1. MS (EI): m/z (%) = 191.0 (35.16) [M+], 152.0 (2.10) [M+ - CH2CN]. HRMS: m/z calcd for C11H13NO2: 191.09460; found: 191.09481.

11

Details on the X-ray structures can be obtained from the Cambridge Crystallographic Data Centre: 15 (CCDC 260273), 22a (CCDC 260274).