Unexpected dimerization reaction of 5-methyl-6,7-methylendioxy-1-tetralone in the presence of TMSCl-ethylene glycol

Unprecedented dimerization reactions of the title compound using TMSCl as reagent and ethylene glycol as solvent has been observed and rationalized


Introduction
During our approach to the synthesis of the hydrophenalene ring system of pseudopterosines, 1 it was necessary to protect the 1-tetralone derivative 1 as cyclic acetal 5 or dithiane 6.Thus, the reaction of 1 with 1,2-ethanedithiol in presence of BF 3 •OEt 2 afforded 6 (88% isolated yield). 2 In contrast, when 1 reacts with ethylene glycol (benzene, reflux) in the presence of TsOH, compound 5 was isolated with maximum (and difficult to reproduce) 47% yield (Figure 1).During the search for an alternative method for the preparation of 5, the use of ethylene glycol as solvent in the presence of trimethylsilyl chloride 3 was considered as an appealing possibility.In this way, when 1 (2,0 mmol) was subjected to reaction with 8,2 mmol of TMSCl in 10 ml of ethylene glycol (rt, 72h), no traces of compound 5 were observed and instead a mixture of compounds 2, 3 and 4 were isolated by column chromatography (SiO 2 , hexane-AcOEt, 20:1).(Scheme 1)

Scheme 1
The structures of these new compounds were established on the basis of their spectroscopic ( 1 H-, 13 C-NMR, MS) and analytical data.Thus, in all cases the 1 H-and 13 C-NMR spectra show double signals which suggest the dimeric nature of these compounds.That was confirmed by MS as well as by the presence of chlorine in compound 2.
A probable reaction for the formation of the major product 2 is depicted in Scheme 2. Reaction of 1 with Me 3 SiCl 4 should afford five-coordinate complex 7 which can exist in equilibrium with cation 8. 5 The nucleophilic attack of ethylene glycol on 8 should give intermediate 9. Now two possible reaction paths are conceivable for 9. Path a) involves the intramolecular addition of the remaining OH group to give the expected and not observed compound 5.Alternatively, chloride ion may act as basic reagent inducing β-elimination reaction (path b) giving intermediate 10 which, by intramolecular reaction with 8 (nucleophilic addition to carbonyl-activated group) of 1 afforded 11.Final nucleophilic substitution reaction of chlorine anion on 11, should give 2.

Scheme 2
Regarding the formation of compounds 3 and 4, these may be formed via a Mukaiyama-type aldol reaction 6 between silylenolether 12 (arising from 8 via Cl -induced enolization) and protonated ketone 1, to give intermediate 13 which, after recovering of catalyst (Me 3 SiCl) and dehydration should afford compound 3. Further aromatization of 3 (probably during the work-up of the reaction) gave 4 (Scheme 3).In summary, the results here presented constitute a convenient procedure for the synthesis of dimeric structures of tetralone derivatives avoiding the use of any organometallic catalytic reagent.

Experimental Section
General Procedures.The reaction was carried out under a positive pressure of dry Ar using freshly distilled solvents under anhydrous conditions.Reagents and solvents were handled by using standard syringe techniques.Ethylene glycol and TMSCl were commercial and used as received.5-Methyl-6,7-methylendioxy-1-tetralone (1) was synthesized as previously described. 7R spectra were recorded on a Perkin-Elmer 297 spectrophotometer. 1 H-NMR and 13 C-NMR were obtained on Varian XL-300 and Bruker AM-300 spectrometers.Silica gel Merck (230-400 mesh) and Merck 60F 254 plates were used for conventional and analytical (TLC) chromatography respectively.