Convergent Formal Synthesis of (±)-Heliannuols A, K, and L from a Common Intermediate

Abstract

The intramolecular titanium-mediated cyclopropanation reaction of an oxa-ester bearing a terminal double bond followed by appropriate oxidation and dehydrohalogenation allows easy access to an aryl-fused oxacyclooctenone, an effective precursor of (±)-heliannuols A, K and L.

bicyclic compounds - cyclization - enones - heterocycles - organometallic reagents - radical reactions - titanium

References

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8

8-Methoxy-2,2,6,9-tetramethyl-2 H -1-benzoxocin-3 (4 H )-one ( 6). Mp: 66 °C.¹H NMR (250 MHz, CDCl₃): δ = 6.88 (s, 1 H), 6.64 (s, 1 H), 5.75 (t, J = 7.5 Hz, 1 H), 3.83 (s, 3 H), 2.98 (d, J = 7.5 Hz, 2 H), 2.21 (s, 3 H), 2.06 (s, 3 H), 1.47 (s, 6 H). ¹³C NMR (63 MHz, CDCl₃): δ = 208.65, 154.52, 145.04, 137.10, 132.82, 127.48, 126.38, 119.31, 108.46, 81.63, 55.50, 40.95, 24.59, 23.77, 16.13. IR (neat): 2984, 2938, 1713, 1504, 1464, 1395, 1205, 1152, 1022 cm^-1. MS (EI): m/z (%) = 260 (72.4)[M⁺], 217 (15.2), 191 (35.5), 190 (49.1), 189 (100), 176 (34.3), 175 (43.8), 159 (8.6), 115 (8.3). HRMS: found 260.1414; C₁₆H₂₀O₃ requires 260.1412.

9

We noted several omissions in the reported data of this compound. [3]
8-Methoxy-2,2,6,9-tetramethyl-5,6-dihydro-2 H -1-benzoxocin-3 (4 H )-one ( 7).
Mp: 71 °C. ¹H NMR (250 MHz, CDCl₃): δ = 6.74 (s, 1 H), 6.58 (s, 1 H), 3.80 (s, 3 H), 3.20-3.02 (m, 1 H), 2.61-2.39 (m, 2 H), 2.15 (s, 3 H), 2.07-1.90 (m, 1 H), 1.79-1.61 (m, 1 H), 1.49 (s, 3 H), 1.45 (s, 3 H), 1.34 (d, J = 7.1 Hz, 3 H). ¹³C NMR (90 MHz, CDCl₃): δ = 212.98, 154.86, 145.96, 136.90, 127.46, 124.37, 108.71, 85.91, 55.45, 36.03, 34.65, 34.46, 24.36, 23.45, 20.43, 15.78. IR (neat): 3038, 2939, 2854, 1713, 1504, 1464, 1397, 1380, 1203, 1144, 1019 cm^-1. MS (EI): m/z (%) = 262 (21.9) [M⁺], 178 (19.3), 165 (100), 163 (4.4), 91 (4.3). HRMS: found 262.1557; C₁₆H₂₂O₃ requires 262.1568.

10 Ballestri M. Chatgilialoglu C. Clark KB. Griller D. Giese B. Kopping B. J. Org. Chem.  1991,  56:  678 

11

We noted omissions in the reported data of this compound. [3]
8-Methoxy-2,2,6,9-tetramethyl-3,4,5,6-tetrahydro-2 H -1-benzoxocin-3-ol ( 8). ¹H NMR (250 MHz, CDCl₃): δ = 6.76 (s, 1 H, cis), 6.72 (s, 1 H, trans), 6.62 (s, 1 H, cis), 6.58 (s, 1 H, trans), 3.81 (s, 6 H), 3.43 (d, J = 9.1 Hz, 2 H), 3.30-3.11 (m, 2 H), 2.16 (s, 6 H), 2.15-1.94 (m, 8 H), 1.62 (br s, 2 H), 1.44 (s, 6 H), 1.38 (s, 6 H), 1.29 (d, J = 7.1 Hz, 6 H). MS (EI, trans isomer): m/z (%) = 264 (26.4) [M⁺], 246 (8.7), 178 (16.0), 166 (21.6), 165 (100). MS (EI, cis isomer): m/z (%) = 264 (17.2) [M⁺], 246 (5.8), 178 (13.1), 166 (17.6), 165 (100). HRMS (trans isomer): found 264.1735; C₁₆H₂₄O₃ requires 264.1725. HRMS (cis isomer): found 264.1716; C₁₆H₂₄O₃ requires 264.1725.

12 Labib GH. Cordier P. Compt. Rend.  1957,  245:  1548 

13

8-Methoxy-4,4,7,9b-tetramethyl-1a,9b-dihydro-2 H -oxireno[ e ][1]benzoxocin-3 (4 H )-one ( 9). Mp: 89 °C. ¹H NMR (250 MHz, CDCl₃): δ = 6.86 (s, 1 H), 6.79 (s, 1 H), 3.85 (s, 3 H), 3.24 (dd, J = 9.6, 4.0 Hz, 1 H), 2.89 (dd, J = 12.4, 4.0 Hz, 1 H), 2.19 (s, 3 H), 2.18-2.11 (m, 1 H), 1.58 (s, 3 H), 1.56 (s, 3 H), 1.37 (s, 3 H). ¹³C NMR (50 MHz, CDCl₃): δ = 207.96, 155.26, 144.27, 131.50, 126.82, 126.53, 109.82, 87.09, 61.25, 59.14, 55.60, 42.50, 25.64, 24.17, 23.62, 16.21. IR (neat): 2984, 2936, 1714, 1505, 1464, 1398, 1378, 1205, 1148, 1020 cm^-1. MS (EI):
m/z (%) = 276 (94.5) [M⁺], 247 (25.0), 219 (77.1), 205 (78.0), 192 (28.7), 189 (100), 178 (15.9), 177 (16.7), 176 (28.0), 175 (50.3), 165 (87.6), 164 (39.9), 163 (39.9), 162 (41.9), 149 (32.4), 91 (26.6), 69 (22.9). HRMS: found 276.1352; C₁₆H₂₂O₃ requires 276.1361.

14 Coogan MP. Haigh R. Hall A. Harris LD. Hibbs DE. Jenkins RL. Jones CL. Tomkinson NCO. Tetrahedron  2003,  59:  7389 

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