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

Santosh J. Gharpure; Suheel Kumar Porwal

doi:10.1055/s-2007-1000847

LETTER

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;

Abstract

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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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Referenzen

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15

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).

16

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.