Asymmetric Synthesis of the Diene Unit of Methyl Sartortuoate via a Temperature-Sensitive Intramolecular Horner-Wadsworth-Emmons (HWE) Reaction

Abstract

The asymmetric synthesis of the diene unit of methyl ­sartortuoate is described. A temperature-sensitive intramolecular Horner-Wadsworth-Emmons reaction was employed for the construction of the 14-membered ring. A Payne rearrangement of an 2,3-epoxy alcohol was utilized for the installation of the hydroxyl group at the C14 position of the diene unit.

asymmetric synthesis - methyl sartortuoate - diene unit - HWE reaction - Payne rearrangement

References and Notes

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10

Compound 15: colorless oil; [α]_D ²⁰ +15.8 (c = 0.50, MeOH). IR (film): 2932, 1717, 1676, 1448, 1184, 1137, 1098, 1037 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 10.09 (d, J = 7.8 Hz, 1 H), 6.14 (s, 1 H), 6.12 (d, J = 7.8 Hz, 1 H), 5.39 (s, 1 H), 5.22 (t, J = 7.5 Hz, 1 H), 4.77 (d, J = 7.2 Hz, 1 H), 4.72 (d, J = 7.2 Hz, 1 H), 4.22 (q, J = 7.2 Hz, 2 H), 4.08-4.11 (m, 1 H), 3.62-3.66 (m, 1 H), 3.39 (s, 3 H), 3.01 (d, J = 7.5 Hz, 2 H), 2.19 (s, 3 H), 1.40-2.10 (m, 8 H), 1.64 (s, 3 H), 1.30 (t, J = 7.2 Hz, 3 H), 1.20 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 191.7, 167.3, 161.6, 139.7, 137.2, 126.2, 124.4, 120.8, 90.7, 77.8, 74.8, 72.67, 60.6, 55.5, 36.0, 31.5, 30.1, 26.5, 24.6, 21.0, 16.1, 14.3, 14.2. ESI-MS: m/z = 409.1 [M + H]⁺, 431.1 [M + Na]⁺. HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₃H₃₆O₆: 431.2404; found: 431.2401.

11

Compound 8: colorless oil; [α]_D ²⁰ +88.4 (c = 0.49, CHCl₃). IR (film): 2979, 2934, 1707, 1448, 1380, 1222, 1145, 1097, 1037, 919 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 6.81 (t, J = 7.2 Hz, 1 H), 5.36 (t, J = 7.5 Hz, 1 H), 4.82 (d, J = 8.1 Hz, 1 H), 4.77 (d, J = 7.5 Hz, 1 H), 4.75 (d, J = 7.5 Hz, 1 H), 4.73 (d, J = 8.1 Hz, 1 H), 4.22 (q, J = 7.2 Hz, 2 H), 3.76-3.80 (m, 1 H), 3.69 (d, J = 5.1 Hz, 1 H), 3.38 (s, 3 H), 3.37 (s, 3 H), 2.70-3.10 (m, 4 H), 2.32-2.40 (m, 1 H), 2.00-2.10 (m, 2 H), 1.80-2.00 (m, 2 H), 1.50-1.70 (m, 3 H), 1.62 (s, 3 H), 1.32 (t, J = 7.2 Hz, 3 H), 1.25 (s, 3 H), 1.19 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 168.0, 142.0, 139.1, 127.8, 123.2, 91.4, 90.9, 79.6, 77.4, 76.4, 75.9, 60.0, 55.6, 55.4, 39.7, 38.4, 33.9, 29.5, 27.7, 23.6, 22.7, 21.4, 15.4, 14.3. ESI-MS: m/z = 463.2 [M + Na]⁺. HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₄H₄₀O₇: 463.2666; found: 463.2685.

12

The stereochemistry of the conjugated double bond is assigned from the chemical shift and the coupling constant data of the vinylic proton, and by analogy with closely related cyclizations.

13 Gao Y. Klunder JM. Hanson RM. Masamune H. Ko SY. Sharpless KB. J. Am. Chem. Soc.  1987,  109:  5765 

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17a

Compound 20: white solid; mp 80-81 °C; [α]_D ²⁰ -234 (c = 0.40, CHCl₃). IR (film): 2942, 1740, 1376, 1243, 1092, 1033 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 6.27 (d, J = 10.5 Hz, 1 H), 6.05 (dd, J = 8.4 Hz, 2 H), 4.22 (d, J = 7.5 Hz, 1 H), 4.83 (d, J = 7.5 Hz, 1 H), 4.71 (d, J = 7.5 Hz, 1 H), 4.65 (d, J = 12.3 Hz, 1 H), 4.37 (d, J = 12.3 Hz, 1 H), 4.92 (d, J = 7.5 Hz, 1 H), 3.97-4.01 (m, 1 H), 3.73 (d, J = 8.4 Hz, 1 H), 3.40 (s, 3 H), 3.32 (s, 3 H), 2.50-2.62 (m, 1 H), 2.15-2.33 (m, 1 H), 2.14-2.15 (m, 8 H), 2.054 (s, 3 H), 2.047 (s, 3 H), 1.74 (s, 3 H), 1.23 (s, 3 H), 1.21 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 170.6, 170.1, 139.0, 134.6, 126.0, 118.1, 91.0, 90.8, 82.7, 79.9, 75.2, 69.0, 68.4, 65.2, 55.7, 55.2, 40.4, 39.8, 30.3, 24.6, 21.1 (2 C), 21.0, 20.0, 19.9, 18.3. ESI-MS: m/z = 521.3 [M + Na]⁺. HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₆H₄₂O₉: 521.2721; found: 521.2743.

17b

The crystallo-graphic data for 20 has been deposited at the Cambridge Crystallographic Data Centre with deposition no. CCDC 632316.

18

Compound 22: colorless oil; [α]_D ²⁰ -254 (c = 0.10, CHCl₃). IR (film): 2981, 2945, 2855, 1734, 1673, 1647, 1440, 1376, 1275, 1244, 1033, 910 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 6.98 (d, J = 10.2Hz, 1 H), 6.25 (d, J = 11.1 Hz, 1 H), 5.95 (d, J = 10.2 Hz, 1 H), 5.03 (d, J = 7.2 Hz, 1 H), 4.82 (d, J = 7.5 Hz, 1 H), 4.69 (d, J = 7.5 Hz, 1 H), 4.42 (d, J = 7.2 Hz, 1 H), 3.98-4.02 (m, 1 H), 3.70-3.73 (m, 1 H), 3.40 (s, 3 H), 3.33 (s, 3 H), 1.80-2.70 (m, 4 H), 2.27 (s, 3 H), 2.00 (s, 3 H), 1.40-1.80 (m, 6 H), 1.83 (s, 3 H), 1.23 (s, 3 H), 1.20 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 190.2, 170.6, 145.2, 140.7, 131.9, 118.3, 91.1, 91.0, 82.5, 80.1, 75.2, 68.5, 68.4, 55.7, 55.3, 40.2, 39.6, 30.1, 27.5, 24.5, 21.3, 21.0, 20.1, 20.0, 18.8. ESI-MS: m/z = 491.1 [M + Na⁺]. HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₅H₄₀O₈: 491.2615; found: 491.2605.

19 Lombardo L. Org. Synth.  1987,  65:  81 

20 Takai K. Kakiuchi T. Kataoka Y. Utimoto K. J. Org. Chem.  1994,  59:  2668 

21 Petasis NA. Bzowej EI. J. Am. Chem. Soc.  1990,  112:  6392 

22

Compound 5: colorless oil; [α]_D ²⁰ -176 (c = 0.05, CHCl₃). IR (film): 2925, 2853, 1742, 1458, 1375, 1240, 1144, 1092, 1072, 1034, 910 cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 6.08-6.13 (m, 3 H), 4.96 (d, J = 7.4 Hz, 1 H), 4.93 (s, 1 H), 4.85 (s, 1 H), 4.84 (d, J = 7.3 Hz, 1 H), 5.03 (d, J = 7.3 Hz, 1 H), 4.39 (d, J = 7.4 Hz, 1 H), 4.03 (dd, J = 3.0 Hz, 1 H), 3.69 (d, J = 8.3 Hz, 1 H), 3.40 (s, 3 H), 3.33 (s, 3 H), 1.40-2.80 (m, 10 H), 1.98 (s, 3 H), 1.88 (s, 3 H), 1.73 (s, 3 H), 1.25 (s, 3 H), 1.21 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 169.9, 143.5, 137.4, 121.2, 119.0, 113.9, 112.9, 91.1, 91.0, 82.7, 80.2, 75.3, 69.8, 68.3, 55.7, 55.2, 40.3, 39.8, 30.4, 29.7, 24.6, 22.8, 21.5, 21.1, 20.2, 18.4. ESI-MS: m/z = 489.4 [M + Na]⁺. HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₆H₄₂O₇: 489.2828; found: 489.2823.