Tetrahedron Letters 30(31) (1989) 4037-4040 Electrosynthesis of gamma-asarone R R Vargas et al. Abstract: g-asarone is synthesised in high yield, and conveniently, by anodic methoxylation of methyl eugenol, at constant current. The method is extremely simple and inexpensive. 2,4,5-trimethoxyallylbenzene (1) is one of the rarer natural allylbenzenes. It was isolated for the first time from [i]Caesulia axillaries[/i] and named g-asarone.[sup]1[/sup] The back and wood of [i]Aniba hostmanniana[/i], an arboreous species of [i]Lauraceae[/i] contain essential oils composed of ca 95% of (1).[sup]2[/sup] The only reported[sup]3[/sup] synthesis of (1) is based on the geneneral sequence of reactions: dimethoxyphenol -> allyl dimethoxyphenyl ether -> allyldimethoxyphenol -> trimethoxyallylbenzene, and the overall yield is less than 30%. Here we report a new synthesis of g-asarone, via the anodic oxidation of methyl eugenol (2) at a platinum electrode in alkaline methanol solution and under controlled current conditions. The average yield, from several experiments, is 80% and the simplicity and low cost clearly show the advantage of this method as compared with the one previously described.[sup]3[/sup] This synthesis is another application of anodic methoxylation, a well established method which has been widely used.[sup]4[/sup] General procedure: The electrolyses were performed in an undivided cell using a Pt foil anode (2.5 x 3.5 cm) and a W wire as cathode. A solution of methyl eugenol (2.8 mmoles) in MeOH (60 mL) containing NaClO4 (6.0 mmoles) and NaOH (30.0 mmoles) was electrolyzed at room temperature (50 mA, 0.0057 Acm[sup]-2[/sup] 3F/mol). After completion, MeOH was removed under reduced pressure [because of the possible formation of explosive perchlorates the mixture should never be taken completely to dryness]. Water added to the residue, the mixture acidulated with hydrochloric acid until pH 4 and extracted with ether. After concentrating under vacuum, g-asarone was isolated by column chromatography (SiO2, hex-EtOAc 3:2) and fully characterised; spectral data were according to the litterature.[sup]2[/sup] When 5.6 moles of (2) were used, under otherwise similar conditions, g-asarone was obtained in lower yields (55%). The reaction probably proceeds through an intermediate (3) which during acid work-up originates product (1). This type of intermediate was observed during the anodic oxidation of dimethoxybenzenes.[sup]5[/sup] Intermediate (3) was isolated by work-up under alkaline conditions and characterised by 1H NMR. When analysed by GC/MS (3) gave a peak the at highest mass m/z 194 instead of the expected 240. This is probably due to a fragmentation, in which a molecule of dimethyl ether is lost, and (3) yields (4). [note: fragmentation and molecule (4) not shown]. The g-asarone obtained was isomerized in alkaline solution quantitatively[sup]3[/sup] into a 5:1 mixture of (E)- and (Z)-2,4,5-trimethoxypropenylbenzenes; the (E) isomer is important as a precursor in a synthesis of magnosalicin.[sup]6[/sup] As the alkaline isomerization of g-asarone showed to be very time consuming, attempts to prepare (E)-2,4,5-trimethoxybenzene via anodic oxidation directly from methyl isoeugenol (5) were made. However no nuclear methoxylation product could be isolated. In a typical experiment, the electrolysis of a solution of (5) (5.7 mmoles) in MeOH (60 mL) containing NaClO4 (6 mmoles) and NaOH (26.0 mmoles) at room temperature (80 mA, 00.91 Acm[sup]-2[/sup], 2F/mol), after work-up as described for methyl-eugenol (2), afforded two products derived from the side-chain methoxylation of (5): 1,2-dimethoxy-1-(3,4-dimethoxyphenyl) propane (6) (2.85 mmoles, 50%, erythro/threo, 2.5:1) and 1-(3,4-dimethoxyphenyl)-2-methoxy-propanol (7) (1.14 mmoles, 20%, erythro/threo, 2:1). Both structures were assigned based on GC/MS, IR and 1H/13C NMR measurements. Eugenol (8) when oxidized under similar conditions as for (2), but to 1F/mol afforded dehydrodieugenol (9)[sup]7[/sup] in almost quanitative yield. This electrochemical dimerization has been reported[sup]8[/sup] but substituting NaClO4 for LiClO4 enabled us to use solutions with eugenol concentrations of up to 0.1 M which is ten times the one originally employed. With LiClO4 and 0.1 M of eugenol the lithium salt of (9) is formed on the electrode impeding the passage of current. References: 1. ON Devgan, MM Bokadia, Aust J Chem 21 (1968) 3001 2. OR Gottlieb, AI de Rocha, Phytochem 11 (1972) 1861 3. AT Shulgin, Can J Chem 43 (1965) 3437 4. For leading references see S Torii, "Electroorganic synthesis: methods and applications" Part 1: Oxidations, monographs in modern chemistry, Vol 15, Kodansha, Tokyo and VCH, Weinheim, 1985. 5. NL Weinberg, B Belleau, Tetrahedron 29 (1973) 279 6. K Mori, M Komatsu, M Kido, K Nakagawa, Tetrahedron 42 (1986) 523 7. AF Dias, Phytochem 27 (1988) 3008 8. A Nishiyama, H Eto, Y Terada, M Iguchi, S Yamamura, Chem Pharm Bull 31 (1983) 2820