Regioselective Oxidative Coupling Approach to the Synthesis of (±)-Matairesinol and (±)-Secoisolariciresinol

Abstract

An efficient method for the synthesis of (±)-matairesinol and (±)-secoisolariciresinol is presented. By using 5-(tert-butyl)ferulic acid as a precursor, a regioselective oxidative coupling step was realized, which gave the desired coupling product in much higher yield (91%) than the literature value (ca. 20%).

(±)-matairesinol - (±)-secoisolariciresinol - synthesis - regioselective - oxidative coupling

References and Notes

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7 Saleh SA. Tashtoush HI. Tetrahedron  1998,  54:  14157 

8

5-(tert-Butyl)ferulic acid (6): white crystalline solid; mp 185-186 °C. IR (neat): 3506, 2957, 1681 cm^-1. ¹H NMR (300 MHz, acetone-d ₆): δ = 1.43 (s, 9 H, CH₃), 3.94 (s, 3 H, OCH₃), 6.38 (d, J = 15.9 Hz, 1 H, H-7), 7.15 (d, J = 1.8 Hz, 1 H, H-2), 7.27 (br s, 1 H, H-6), 7.62 (d, J = 15.9 Hz, 1 H, H-8). ¹³C NMR (75 MHz, acetone-d ₆): δ = 30.0, 35.1, 56.5, 108.3, 115.4, 122.0, 125.9, 136.0, 146.1, 148.0, 148.6, 168.5. MS (EI): m/z (%) = 250(8) [M⁺], 235 (100) [M - CH₃]⁺. HRMS (EI): m/z calcd for C₁₄H₁₈O₄ + H: 251.1278; found: 251.1281.

9 Rosenwald HR. J. Am. Chem. Soc.  1952,  74:  4602 

10 Coffield TH. Filbey AH. Ecke GG. Kolka AJ. J. Am. Chem. Soc.  1957,  79:  5019 

11

Compound 7: white solid; mp 218-220 °C. IR (neat): 3391, 2950, 1753, 1693, 1652, 1151 cm^-1. ¹H NMR (300 MHz, acetone-d ₆): δ = 1.40 (s, 18 H, CH₃), 3.88 (s, 6 H, OCH₃), 4.11 (d, J = 1.2 Hz, 2 H, H-1, -5), 5.79 (br s, 4 H, H-2, H-6), 6.96 (s, 2 H, H-2′, H-2′′), 6.97 (s, 2 H, H-6′, H-6′′). ¹³C NMR (75 MHz, acetone-d ₆): δ = 29.5 (CH₃), 35.0 (CMe₃), 48.9 (C-1, 5), 56.3 (OCH₃), 83.4 (C-2,6), 107.1 (C-2′, -2′′), 117.3 (C-6′, -6′′), 129.1 (C-1′, -1′′), 135.9 (C-5′, -5′′), 145.9 (C-4′, -4′′), 148.3 (C-3′, -3′′), 175.8 (C=O). MS (EI): m/z (%) = 498 (62) [M⁺], 483 (40) [M - CH₃]⁺, 57 (100). HRMS (EI): m/z calcd for C₂₈H₃₄O₈ + H: 499.2326; found: 499.2328.

12

Compound 8: white solid; mp 199-200 °C. IR (neat): 3525, 2955, 1701, 1593, 1297 cm^-1. ¹H NMR (300 MHz, acetone-d ₆): δ = 1.34 (s, 18 H, CH₃), 2.74-2.79 (m, 2 H, CH), 2.86-3.01 (m, 4 H, ArCH₂), 3.73 (s, 6 H, OCH₃), 6.68 (br s, 4 H, H-2, H-2′, H-6, H-6′). ¹³C NMR (75 MHz, acetone-d ₆): δ = 29.9, 35.1, 37.7, 50.8, 56.4, 110.8, 120.1, 130.4, 135.3, 143.6, 147.7, 178.3. EIMS: m/z (%) = 484 (10) [M - 18]⁺, 227 (10), 193 (100). HRMS (EI): m/z calcd for C₂₈H₃₈O₈ + Na: 525.2459; found: 525.2454.

13

Compound 9: pale yellow gum. IR (neat): 3524, 2955, 1767, 1595, 1232 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.36 (s, 9 H, CH₃), 1.39 (s, 9 H, CH₃), 2.40-2.70 (m, 4 H, H-7′, H-8, H-8′), 2.91 (dd, J = 14.0, 6.3 Hz, 1 H, H-7), 3.03 (dd, J = 14.0, 4.8 Hz, 1 H, H-7), 3.79 (s, 3 H, OCH₃), 3.82 (s, 3 H, OCH₃), 3.88 (dd, J = 9.3, 6.6 Hz, 1 H, H-9′,), 3.96 (dd, J = 9.0, 6.6 Hz, 1 H, H-9′), 5.89 (s, 1 H, OH), 5.91 (s, 1 H, OH), 6.33 (d, J = 1.2 Hz, 1 H, H-2′), 6.54 (d, J = 1.2 Hz, 1 H, H-2), 6.59 (d, J = 1.2 Hz, 1 H, H-6′), 6.69 (br s, 1 H, H-6). ¹³C NMR (75 MHz, CDCl₃): δ = 29.6, 29.7, 34.8, 35.2, 38.9, 41.3, 47.1, 56.3, 71.6, 108.7, 109.5, 119.3, 120.1, 128.1, 128.3, 135.5, 135.8, 143.1, 143.2, 146.8, 147.0, 179.2. MS (EI): m/z (%) = 470 (8) [M⁺], 193 (100). HRMS (EI): m/z calcd for C₂₈H₃₈O₆ + NH₄: 488.3007; found: 488.3009.

14 Tashiro M. Yamato T. J. Org. Chem.  1979,  44:  3037 

15

Compound 10: colorless oil. IR(neat): 3526, 2956, 1730, 1595, 1372 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.18 (t, J = 6.9 Hz, 6 H, CH₂CH₃), 1.36 (s, 18 H, CH₃), 2.86-2.89 (m, 2 H, CH), 2.90-2.96 (m, 4 H, ArCH₂), 3.77 (s, 6 H, OCH₃), 4.08 (q, J = 6.9 Hz, 4 H, CH₂CH₃), 5.87 (s, 2 H, OH), 6.43 (s, 2 H, H-2, H-2′), 6.65 (s, 2 H, H-6, H-6′). ¹³C NMR (75 MHz, CDCl₃): δ = 14.1, 29.3, 34.5, 35.7, 48.1, 55.9, 60.5, 108.8, 119.7, 128.2, 134.6, 142.6, 146.4, 173.7. MS (EI): m/z (%) = 558 (14) [M⁺], 279 (10), 193 (88), 149 (100). HRMS (EI): m/z calcd for C₃₂H₄₆O₈ + H: 559.3265; found: 559.3267.

16

Compound 11: colorless oil. IR (neat): 3429, 2934, 1727, 1516 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.21 (t, J = 7.2 Hz, 6 H, CH₂CH₃), 2.83-2.86 (m, 2 H CH), 2.91-2.96 (m, 4 H, ArCH₂), 3.78 (s, 6 H, OCH₃), 4.10 (q, J = 7.2 Hz, 4 H, CH₂CH₃), 5.49 (s, 2 H, OH), 6.48 (s, 2 H, H-2, H-2′), 6.59 (d, J = 8.1 Hz, 2 H, H-6, H-6′), 6.79 (d, J = 8.1 Hz, 2 H, H-5, H-5′). ¹³C NMR (75 MHz, CDCl₃): δ = 14.1, 35.3, 47.5, 55.6, 60.6, 112.2, 114.0, 121.9, 130.5, 144.1, 146.3, 179.5. MS (EI): m/z (%) = 446 (10) [M⁺], 277 (31), 223 (24), 177 (28), 149 (53), 137 (100). HRMS (EI): m/z calcd for C₂₄H₃₀O₈ + H: 447.2013; found: 447.2021.

17

(±)-Matairesinol (1): pale yellow solid; mp 66-67 °C. IR (neat): 3418, 2935, 1760, 1606, 1239 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 2.40-2.63 (m, 4 H, H-7, H-8, H-8′), 2.87 (dd, J = 14.2, 6.8 Hz, 1 H, H-7′), 2.95 (dd, J = 14.2, 5.2 Hz, 1 H, H-7′), 3.80 (s, 6 H, OCH₃), 3.89 (dd, J = 9.2, 7.2 Hz, 1 H, H-9), 4.15 (dd, J = 8.8, 7.2 Hz, 1 H, H-9), 5.64 (br s, 2 H, OH), 6.40 (d, J = 1.6 Hz,1 H, H-2), 6.50 (dd, J = 8.0, 2.0 Hz, 1 H, H-6), 6.59 (dd, J = 8.0, 2.0 Hz, 1 H, H-6′), 6.60 (br s, 1 H, H-2′), 6.79 (d, J = 8.4 Hz,1 H, H-5), 6.81 (d, J = 8.4Hz, 1 H, H-5′). ¹³C NMR (75 MHz, DMSO-d ₆): δ = 33.7, 36.9, 40.9, 45.7, 55.4, 55.5, 70.8, 112.6, 113.4, 115.4, 120.7, 120.6, 128.9, 129.7, 144.9, 145.1, 147.4, 147.5, 178.6. MS (EI): m/z (%) = 358 (4) [M⁺], 137 (100). HRMS (EI): m/z calcd for C₂₀H₂₂O₆ + NH₄: 376.1755; found: 376.1754.

18

(±)-Secoisolariciresinol (2): white solid; mp 116-117 °C. IR (neat): 3351, 2933, 1515 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.85 (br s, 2 H, H-8, H-8′), 2.64 (dd, J = 13.5, 6.9 Hz, 2 H, H-7, H-7′), 2.74 (dd, J = 13.5, 8.1 Hz, 2 H, H-7, H-7′), 3.54 (dd, J = 12, 4.2 Hz, 2 H, H-9, H-9′), 3.78-3.85 (m, 2 H, H-9, H-9′), 3.81 (s, 6 H, OCH₃), 6.58 (s, 2 H, H-2, H-2′), 6.62 (d, J = 8.4 Hz, 2 H, H-6, H-6′), 6.80 (d, J = 8.4 Hz, 2 H, H-5, H-5′). ¹³C NMR (75 MHz, CDCl₃): δ = 35.9, 43.8, 55.8, 60.8, 111.4, 114.1, 121.7, 132.4, 143.8, 146.4. MS (EI): m/z (%) = 362 (11) [M⁺], 277 (6), 189 (6), 137 (100). HRMS (EI): m/z calcd for C₂₀H₂₆O₆ + NH₄: 380.2068; found: 380.2061.

19 Ahmed R. Lehrer M. Stevenson R. Tetrahedron  1973,  29:  3753