Efficient Synthesis of Polycycles by Electrocyclizations of Substituted Trihydroxybenzenes: Synthesis of Rubranine and Deoxybruceol

Abstract

A new synthetic route for biologically interesting polycycles with a citran and a cyclol nucleus was developed starting from several substituted trihydroxybenzenes. This methodology was applied successfully to the synthesis of two natural products, rubranine and deoxybruceol.

Key words

polycycles - citran - cyclol - electrocyclization - rubranine - deoxybruceol

References and Notes

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13

Spectral data for 11: ¹H NMR (300 MHz, CDCl₃): δ = 14.03 (1 H, s), 6.67 (1 H, d, J = 10.1 Hz), 6.61 (1 H, d, J = 10.1 Hz), 5.38 (1 H, d, J = 10.1 Hz), 5.37 (1 H, d, J = 10.1 Hz), 5.10-5.03 (4 H, m), 2.64 (3 H, s), 2.20-1.87 (14 H, m), 1.79-1.65 (2 H, m), 1.65 (6 H, s), 1.56 (6 H, s), 1.55 (6 H, s), 1.43 (3 H, s), 1.40 (3 H, s). IR (neat): 2926, 1640, 1601, 1429, 1366, 1296, 1154, 1105, 1026, 1001, 895, 729 cm^-1. HRMS: m/z [M⁺] calcd for C₃₈H₅₂O₄: 572.3866; found: 572.3868.

14

Spectral data for 12: ¹H NMR (300 MHz, CDCl₃): δ = 13.29 (1 H, s), 6.01 (1 H, s), 5.18-5.13 (1 H, m), 2.72 (1 H, br s), 2.58 (3 H, s), 2.28-1.98 (8 H, m), 1.69 (3 H, s), 1.63 (3 H, s), 1.50-1.40 (1 H, m), 1.36 (3 H, s), 1.32-1.23 (2 H, m) 1.05 (3 H, s). IR (neat): 2928, 1622, 1485, 1433, 1364, 1294, 1161, 1061, 961, 824, 772, 735 cm^-1. HRMS: m/z [M⁺] calcd for C₂₃H₃₀O₄: 370.2144; found: 370.2142

15

Spectral data for 23: mp 216-217 °C. ¹H NMR (300 MHz, CDCl₃): δ = 13.95 (1 H, s), 8.19 (1 H, d, J = 15.7 Hz), 7.74 (1 H, d, J = 15.7 Hz), 7.51 (2 H, d, J = 8.1 Hz), 7.17 (2 H, d, J = 8.1 Hz), 6.08 (1 H, s), 2.77 (1 H, br s), 2.37 (3 H, s), 2.24-2.06 (2 H, m), 1.88-1.82 (1 H, m), 1.64 (3 H, s), 1.50-1.41 (1 H, m), 1.38 (3 H, s), 1.30-1.24 (1 H, m), 1.05 (3 H, s), 0.87-0.83 (2 H, m). IR (KBr): 3449, 2924, 1618, 1549, 1478, 1235, 1181, 1163, 1142, 1078, 1020, 988, 881, 823 cm^-1. HRMS: m/z [M⁺] calcd for C₂₆H₂₈O₄: 404.1988; found: 404.1985.

16

Spectral data for 24: mp 208-209 °C. ¹H NMR (300 MHz, CDCl₃): δ = 14.04 (1 H, s), 8.13 (1 H, d, J = 15.6 Hz), 7.74 (1 H, d, J = 15.6 Hz), 7.56 (2 H, d, J = 8.7 Hz), 7.17 (2 H, d, J = 8.7 Hz), 6.08 (1 H, s), 3.84 (3 H, s), 2.77 (1 H, br s), 2.22-2.08 (2 H, m), 1.88-1.83 (1 H, m), 1.64 (3 H, s), 1.50-1.40 (1 H, m), 1.38 (3 H, s), 1.32-1.23 (1 H, m), 1.05 (3 H, s), 0.92-0.80 (2 H, m). IR (KBr): 3445, 1622, 1553, 1510, 1480, 1422, 1352, 1233, 1171, 1022, 829 cm^-1. HRMS: m/z [M⁺] calcd for C₂₆H₂₈O₅: 420.1937; found: 420.1938.

19

Typical Procedure for Compounds 12 and 16-22
To a solution of trihydroxybenzenes (1.0 mmol) and citral or trans,trans-farnesal (2.0 mmol) in DMF (20 mL) was added ethylenediamine diacetate (36 mg, 0.2 mmol) at r.t. The reaction mixture was stirred at 100 °C for 10-12 h and then cooled to r.t. Then H₂O was added and the solution was extracted with EtOAc. Evaporation of solvent and purification by column chromatography on silica gel gave the products.