The Rhodium Carbenoid Route to 3-Aryl-4-hydroxycoumarins: Synthesis of Derrusnin

Abstract

3-Aryl-4-hydroxycoumarins have been obtained in satisfactory yields and selectivity through a Rh(II)-mediated arylation of diazocoumarin. The utility of this approach is demonstrated by ­synthesis of the natural product derrusnin.

Key words

arene - arylations - diazo compounds - rhodium - heterocycles

References

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12

Temperature of 130 °C was used because it represents the right compromise between formation of Rh(II)-carbenoid and thermal decomposition of diazocoumarin 3 (checked by DCS-TGA analysis).

21

5,7-Dimethoxy-3-diazo-benzopyran-2,4 (3H)dione (9): pale yellow powder. ¹H NMR (400 MHz, CDCl₃): δ = 6.37 (d, J = 2.5 Hz, 1 H), 6.33 (d, J = 2.5 Hz, 1 H), 3.96 (s, 3 H), 3.90 (s, 3 H) ppm. IR: ν = 2168, 1720, 1643, 1612 cm^-1. MS (CI, isobutane): m/z (%) = 217 (100) [MH]⁺. Anal. Calcd for C₁₁H₈N₂O₃ (216.2): C, 61.11; H, 3.73; N, 12.96. Found: C, 61.02; H, 3.98; N, 12.76.

25

General Procedure (Method A).
Unless stated otherwise, diazocoumarin 3 (1 mmol), was suspended in the aromatic compound (5 mL) and Rh(II) catalyst (0.02 mmol) was added. The mixture was brought to reflux under N₂ and vigorous stirring for several hours, checking by TLC (CH₂Cl₂-EtOAc, 97:3) or HPLC the reaction progress. The crude reaction mixture was evaporated to dryness by rotary evaporator and the residual submitted to silica gel chromatography.
Representative Arylation Procedure (Method B; Preparation of 10). Diazocoumarin 9 (248 mg, 1.5 mmol), 1,3-benzodioxole (1.72 mL, 15 mmol) and Rh₂ (pfb)₄ (317 mg, 0.3 mmol) were combined in C₆F₆ (5 mL) in a dry 25 mL heavy-walled Pyrex tube, equipped with a magnetic stir bar, flushed with N₂ and sealed with a screw cap fitted Teflon^® septum. The reaction was warmed to 130 °C (oil bath) with stirring behind a protective shield until TLC (CH₂Cl₂- EtOAc, 97:3) or HPLC [Symmetry C8-Waters (4.6 mm/150 mm); phosphate buffer-TEA(pH 7)-MeCN; 1 mL/min] indicated the disappearance of the starting 9 (7 h) [CAUTION: While we observed no problems with the thermal stability of diazocoumarins (viz., 3 and 9), care should be exercised]. The cooled solution was poured directly onto the top of a silica gel column, and the column was flushed with hexane to remove excess 1,3-benzodioxole and C₆F₆. Elution was then continued with a 49:1 mixture of CH₂Cl₂-EtOAc to afford 5,7-dimethoxy-4-hydroxy-3-(3,4-methylenedioxy-phenyl)chromen-2-one (10, 359mg, 70%) as light yellow needles after crystallization from EtOH, mp 233 °C [Lit. [6] 234 °C].