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Synlett 2005(6): 0927-0930  
DOI: 10.1055/s-2005-864808
LETTER
© Georg Thieme Verlag Stuttgart · New York

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

Luca Goldonia, Giancarlo Cravottob, Andrea Penonic, Stefano Tollari*c, Giovanni Palmisano*c
a Dipartimento di Chimica Inorganica Metallorganica e Analitica, Università degli Studi di Milano, Via Venezian 21, 20133 Milano, Italy
b Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino, Via Giuria 9, 10235 Torino, Italy
c Dipartimento di Scienze Chimiche e Ambientali, Università degli Studi dell’Insubria, Via Valleggio 11, 22100 Como, Italy
Fax: +39(031)2386449; e-Mail: giovanni.palmisano@uninsubria.it.;
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Publication History

Received 21 January 2005
Publication Date:
23 March 2005 (online)

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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

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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).

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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.

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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].