The methylenedioxy group is of special interest due to its occurrence in natural products¹ and as a protecting group in organic synthesis². However, its use has been limited due to the difficulty in formation of this ring system.

There have been several methods published in recent years describing improved methods for formation of methylenedioxy groups in the presences of a bronze³, nickel oxide⁴, or cupric oxide⁵ catalyst in dimethylsulfoxide (DMSO) or N,N-dimethylformamide (DMF). High yields of methylated catechols have also been obtained with excess potassium or cesium fluoride in DMF,⁶ with potassium carbonate in DMF,⁷ or with sodium hydride in hexamethylphosphoric triamide.⁸ Methylenedioxy groups have also been formed in the absence of a dipolar aprotic solvent by using a phase transfer catalyst at reflux.⁹ Although each of the methods cited has its merits, they afforded varying degrees of success when employed on the methylenation of 5,6-dihydroxy-1-tetralones 1 (R = H, F, or CH₃). In fact, numerous attempts to methylenate 1 (R = F) under previous methodology^3,5,6,8,9 provided the desired methylenedioxy derivative 2 (R = F) in low to moderate yield (10-50%).

Herein we wish to report a simple high yielding methylenation of catechols which requires neither strong base, special precautions, nor controlled addition of reagents. The reaction of catechol 1 (R = F) with bromochloromethane in DMF at 110°C in the presence of cesium carbonate provided the desired methylendioxy derivative 2 (R = F) in 86% yield.

Table I summarizes the optimization of this reaction on the readily available catechol 1 (R = H). Although potassium carbonate has been utilized as a base in this type of reaction,⁷ cesium carbonate provides higher and more consistent yields¹⁰ of methylenated product (Examples 1, 2). Also, less reactive catechols such as 1 (R = F) are methylenated in low to moderate yield when potassium carbonate is utilized as the base, as opposed to the high yield obtained with cesium carbonate.¹¹ The reaction can also be conducted in acetonitrile in excellent yield, although the reaction time is increased due to the lower reaction temperature (Example 6). No intermolecular O-alkylation products were observed in either solvent. However, trace amounts of 1-hydroxy-2-methyl-5,6- methylenedioxy-naphthalene were occasionally observed, upon scale-up.

Table II contains a representative sampling of catechols that have been subjected to this method.¹² The reaction can be carried out in either DMF or CH₃CN, but higher yields are obtained in DMF when employing less reactive substrates. The increased effectiveness of DMF over CH₃CN as solvent can be attributed in most cases to (a) the overall solubility of the starting material, (b) the solubility of the corresponding cesium phenoxides, and (c) the increased rate of reaction due to the elevated temperature obtainable in DMF. The reaction has also been extended to the preparation of (β-hydrastine 3 from the corresponding dihydroxy derivative 4.¹³ Previous attempts to methylenate this compound provided only decomposition products,⁶ whereas the present method provided (β-hydrastine in 70% after 4 hours at reflux in acetonitrile.

In summary, this method for the methylenation of catechols should find general utility, especially in cases where the base sensitivity of the catechol and/or product is a critical issue. Furthermore, the reaction works exceedingly well on catechols which are deactivated by neighboring electron withdrawing groups and/or ring deactivating groups.