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Synlett 2008(2): 242-246  
DOI: 10.1055/s-2007-1000847
LETTER
© Georg Thieme Verlag Stuttgart · New York

Stereoselective Synthesis of New Oxa-Cages via Alkyl Radical Cyclization to Vinylogous Carbonates

Santosh J. Gharpure*, Suheel Kumar Porwal
Department of Chemistry, Indian Institute of Technology Madras, Chennai 600036, India
Fax: +91(44)22574202; e-Mail: sjgharpure@iitm.ac.in;
Further Information

Publication History

Received 19 September 2007
Publication Date:
21 December 2007 (online)

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Abstract

An efficient strategy is developed for the stereoselective synthesis of unsymmetrical dioxa-cage compounds containing ether linkages employing a 6-exo-trig alkyl radical cyclization to vinylogous carbonates. The radical precursors are obtained from the Diels-Alder adducts via iodoetherification and conversion of the alcohol moiety to vinylogous carbonate. The formation of mono-oxa-cage compounds via an intramolecular 5-exo-trig alkyl radical cyclization to olefin is also described.

Key words

oxa-cages - radical cyclization - vinylogous carbonates - Diels-Alder adducts

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All the compounds exhibited spectral data consistent with their structures. Melting point, IR, NMR (1H and 13C) and HRMS spectral data for some of the compounds are as follows:
Oxa-cage 7a: IR (neat): 2940, 2871, 1730, 1459, 1382, 1309, 1288, 1245, 1173, 1144, 1110, 1096, 1078, 1070, 1032, 1018, 980, 911, 764 cm-1. 1H NMR (400 MHz, CDCl3): δ = 4.35 (dd, J = 7.9, 4.7 Hz, 1 H), 4.17-4.08 (m, 2 H), 4.04 (d, J = 11.9 Hz, 1 H), 3.99 (d, J = 8.0 Hz, 1 H), 3.91 (ddd, J = 7.5, 5.6, 1.9 Hz, 1 H), 3.70-3.65 (m, 2 H), 2.92 (ABX, J = 15.7, 7.8 Hz, 1 H), 2.66-2.62 (m, 1 H), 2.63 (ABX, J = 15.7, 5.6 Hz, 1 H), 2.38 (dt, J = 10.2, 4.4 Hz, 1 H), 1.92-1.85 (m, 2 H), 1.56 (ddd, J = 7.8, 5.2, 2.5 Hz, 1 H), 1.47 (AB, J = 10.6 Hz, 1 H), 1.32 (AB, J = 10.6 Hz, 1 H), 1.24 (t, J = 7.2 Hz, 3 H). 13C NMR (100 MHz, CDCl3, DEPT): δ = 172.39 (C), 79.21 (CH), 71.61 (CH), 69.12 (CH2), 65.75 (CH2), 60.44 (CH2), 50.05 (CH), 41.42 (CH), 40.84 (CH), 39.29 (CH), 38.95 (CH2), 37.14 (CH), 33.07 (CH2), 14.32 (CH3). ESI-HRMS: m/z calcd for C14H21O4 [M+ + H]: 253.1440; found: 253.1447.
Oxa-cage 7f: mp 94-96 °C. IR (neat): 2931, 2864, 1728, 1460, 1381, 1271, 1260, 1247, 1173, 1100, 1077, 1060, 1003, 987, 920, 753 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.39-7.30 (m, 4 H), 5.08 (d, J = 8.4 Hz, 1 H), 4.74 (d, J = 2.8 Hz, 1 H), 4.49 (ddd, J = 8.3, 5.8, 0.9 Hz, 1 H), 4.15 (t, J = 6.3 Hz, 1 H), 4.08 (q, J = 7.1 Hz, 2 H), 2.52 (ABX, J = 14.7, 5.8 Hz, 1 H), 2.44 (ABX, J = 14.7, 8.3 Hz 1 H), 2.40-2.33 (m, 3 H), 1.99 (br s, 1 H), 1.90-1.83 (m, 2 H), 1.74-1.66 (m, 3 H), 1.18 (t, J = 7.1 Hz, 3 H). 13C NMR (100 MHz, CDCl3, DEPT): δ = 171.38 (C), 136.94 (C), 136.13 (C), 130.60 (CH), 129.37 (CH), 129.26 (CH), 128.39 (CH), 77.78 (CH), 77.23 (CH), 72.82 (CH), 65.45 (CH), 60.38 (CH2), 41.68 (CH2), 41.51 (CH), 40.93 (CH), 40.58 (CH), 32.42 (CH), 23.95 (CH2), 22.40 (CH), 16.43 (CH2), 14.34 (CH3). ESI-HRMS: m/z calcd for C21H25O4 [M+ + H]: 341.1753; found: 341.1745.
Alcohol 9: mp 115-117 °C. IR (neat): 3411, 3029, 2928, 2863, 1460, 1381, 1274, 1261, 1103, 1060, 1036, 1017, 999, 985, 960, 752, 729 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.40-7.29 (m, 4 H), 5.09 (d, J = 8.4 Hz, 1 H), 4.74 (d, J = 2.6 Hz, 1 H), 4.34 (dd, J = 9.7, 2.7 Hz, 1 H), 4.13 (t, J = 6.2 Hz, 1 H), 3.68 (m, 2 H), 3.12 (t, J = 5.5 Hz, 1 H), 2.43-2.33 (m, 3 H), 2.03 (br s, 1 H), 1.94-1.84 (m, 2 H), 1.76-1.66 (m, 4 H), 1.51 (dq, J = 14.0, 3.8 Hz, 1 H). 13C NMR (100 MHz, CDCl3, DEPT): δ = 136.84 (C), 135.96 (C), 130.52 (CH), 129.49 (CH), 129.21 (CH), 128.50 (CH), 77.63 (CH), 77.25 (CH), 72.75 (CH), 70.19 (CH), 62.20 (CH2), 42.37 (CH), 40.80, (CH), 40.50 (CH), 38.84 (CH2), 32.46 (CH), 24.00 (CH2), 22.83 (CH), 16.38 (CH2). ESI-HRMS: m/z calcd for C19H23O3 [M+ + H]: 299.1647; found: 299.1653.
Oxa-cage 10b: IR (neat): 2937, 2867, 1705, 1639, 1619, 1323, 1189, 1126, 1047, 1006, 981, 911, 882 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.50 (d, J = 12.6 Hz, 1 H), 5.20 (d, J = 12.6 Hz, 1 H), 4.37 (d, J = 18.0 Hz, 2 H), 4.16 (q, J = 7.1 Hz, 2 H), 4.08 (t, J = 8.1 Hz, 1 H), 2.22 (ddd, J = 14.0, 9.0, 4.6 Hz, 1 H), 2.14-2.05 (m, 2 H), 1.96-1.89 (m, 3 H), 1.82 (d, J = 5.1 Hz, 1 H), 1.78-1.63 (m, 2 H), 1.63-1.50 (m, 2 H), 1.38-1.32 (m, 1 H), 1.27 (t, J = 7.1 Hz, 3 H). 13C NMR (100 MHz, CDCl3, DEPT): δ = 168.17 (C), 161.47 (CH), 97.73 (CH), 79.09 (CH), 78.39 (CH), 77.69 (CH), 59.92 (CH2), 41.22 (CH), 40.94 (CH), 38.66 (CH), 36.64 (CH), 35.85 (CH), 25.04 (2C, CH, CH2), 22.09 (CH2), 17.08 (CH2), 14.52 (CH). ESI-HRMS: m/z calcd for C17H22O4Na [M+ + Na]: 313.1416; found: 313.1409.
Oxa-cage 12: mp 165-167 °C. IR (neat): 3102, 2968, 2880, 1725, 1628, 1542, 1461, 1344, 1284, 1273, 1169, 1075, 1012, 905, 730 cm-1. 1H NMR (400 MHz, CDCl3): δ = 9.22 (t, J = 2.1 Hz, 1 H), 9.14 (d, J = 2.1 Hz, 2 H), 5.37 (t, J = 8.5 Hz, 1 H), 4.60 (t, J = 4.2 Hz, 1 H), 4.35 (d, J = 4.2 Hz, 1 H), 2.52 (br s, 1 H), 2.45-2.33 (m, 3 H), 2.19 (q, J = 5.6 Hz, 1 H), 1.83-1.76 (m, 3 H), 1.58 (AB, J = 10.8 Hz, 1 H), 1.31 (AB, J = 10.8 Hz, 1 H). 13C NMR (100 MHz, CDCl3, DEPT): δ = 162.36 (C), 148.80 (C), 134.41 (C), 129.53 (CH), 122.47 (CH), 85.08 (CH), 77.94 (CH), 72.04 (CH), 47.89 (CH), 44.05 (CH), 39.68 (CH), 39.50 (CH), 39.06 (CH), 34.31 (CH), 31.60 (CH2), 24.26 (CH2).

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Crystal data for alcohol 9: formula: C19H22O3; unit cell parameters: a = 14.4267(16), b = 6.2541(7), c = 15.9204(17); space group: Pca2(1); CCDC number 652177.
Crystal data for oxa-cage 12: formula: C18H16N2O7; unit cell parameters: a = 29.6325(10), b = 5.9688(2), c = 21.6208(8), β = 121.391(3), space group: C(2)/c; CCDC number 652178. CCDC 652177 and CCDC 652178 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.