Attempted cycloaromatization of α-arylmethyl sulfones with 2-bis(methylthio)methylene-1-tetralone: unexpected formation of 2-aryl-3-(methylthio)-4,5-dihydronaphtho[1,2-b

Base-induced conjugate addition-elimination of α -arylmethyl sulfones to α -oxoketene dithioacetal 1 followed by acid-induced cyclization affords 2-phenyl-3-(methylthio)-4,5-dihydronaphtho[1,2-b ]furans which could be converted to parent aromatized products by DDQ dehydrogenation followed by Raney-Ni dethiomethylation. The approach was found to be amenable to a variety of sulfone components.


Scheme1
We further considered of interest at this juncture to use arylmethylsulfones (with sulfone as activating group) instead of arylacetonitriles in these cycloaromatizations since aryl sulfones can be more easily removed from the cycloaromatized products under milder conditions, unlike its nitrile counterpart.We have therefore investigated base-induced conjugate addition of few arylmethylsulfones such as 3a-b, 9 and 14 (Schemes 2-4) with α-oxoketene dithioacetal 1, leading to the conjugate adducts 4a-b, 10 and 15, respectively, in excellent yields (Schemes 2-4).However, attempted acid-induced cyclization of these adducts yielded the unexpected naphthofuran derivatives instead of the desired angularly cycloaromatized products.The results of these studies are presented in this paper.
The probable mechanism for the formation of the unexpected naphthofurans from the conjugate adducts is depicted in the Scheme 5.It appears that the highly acidic benzylic proton of adducts 4, 10, and 15 rapidly tautomerizes in acidic medium to the enol 18 which undergoes intramolecular cyclization and elimination of phenyl sulfinic acid to afford the observed dihydronaphthofuran products 6a (Scheme 5). 11However, the expected pathway leading to benzo[c]phenanthrene 5 (or 11, 16) through intramolecular cyclodehydration on carbonyl group via participation of aromatic ring appears to be hindered due to steric crowding in the cyclization intermediate (or transition state) 19 due to the presence of two adjacent bulkier aryl sulfonyl and methylthio groups.

Experimental Section
General. 1 H NMR (400 MHz) and 13 C NMR (100 MHz) spectra were recorded on Jeol JNM Lambda Spectrometer with CDCl3 as the solvent and TMS as an internal standard.Melting points were measured using Mel-Temp apparatus and are uncorrected.IR spectra were recorded on a Perkin Elmer 1320 spectrometer.Mass spectra (FAB) were recorded on Jeol SX 102/DA-6000 Mass Spectrometer/Data system.Elemental analyses were carried out on Elementar Vario EL III analyzer.Column chromatography was carried out using silica gel (100-200 mesh).THF and dioxane were distilled over sodium benzophenone ketyl prior to use.KOt-Bu, H3PO4 and DDQ were purchased from standard firms.Raney Ni (W2) was prepared according to the reported procedure. 132-Bis(methylthio)methylene-1-tetralone was prepared according to earlier reported procedure. 14The corresponding benzylphenyl sulfone, (3,4-dimethoxy)benzylphenyl sulfone, (1-naphthyl)benzylphenyl sulfone, and (2-naphthyl)benzylphenylsulfone were prepared according to the reported procedure. 15neral procedure for the preparation of conjugate adducts (4a-b, 10, 15) To a stirring solution of potassium tert-butoxide (0.78 g, 7 mmol) in THF (20 mL) at -78 °C, a solution of arylbenzylsulfone (5 mmol) in THF (20 mL) was added under nitrogen atmosphere followed by further stirring for 45 min at the same temperature.A solution of tetralone S,S-acetal 1 (1.25 g, 5 mmol) in THF (10 mL) was added at -78 °C and the reaction mixture was further stirred for three hours at the same temperature.It was then brought to room temperature during 45 min and stirred at room temperature overnight.The reaction mixture was then poured into icecold saturated solution of NH4Cl (20 mL), extracted with CHCl3 (3x50 mL) and the combined organic extracts were washed with water (3x50 mL), dried (Na2SO4) and concentrated to give adduct (TLC single spot) which were used as such for further acid-induced cyclization.The adduct 10 from 1-(naphthylmethyl)sulfone could be obtained in pure form after column chromatography over silica gel and its spectral and analytical data is given below.

General procedure for the cyclization of adducts 4a-b, 10 and 15 with orthophosphoric acid: synthesis of 2-aryl-3-(methylthio)-4,5-dihydronaphtho[1,2-b]furans
The crude adducts (5 mmol) obtained from the previous experiments were dissolved in H3PO4 (20 mL, 85%) and the reaction mixture was heated with stirring at 80-100 °C for 5-6 h (monitored by TLC).It was then cooled, poured into ice-cold water (150 mL), extracted with CHCl3 (3x50 mL) and the combined organic layer was washed with water (3x50 mL) and dried over anhydrous Na2SO4.The solvent was evaporated under reduced pressure to give crude products which were purified by column chromatography over silica-gel using hexane-ethyl acetate (97:3) as eluent.

General procedure for the dehydrogenation of dihydronaphthofurans with DDQ
The suspension of dihydronaphthofuran (5 mmol) and DDQ (7 mmol) in dioxane (50 mL) was refluxed with stirring for 6-8 h (monitored by TLC).The solvent was evaporated under reduced pressure and the concentrated solution was poured into water (100 mL), extracted with CHCl3 (3x50 mL), dried (Na2SO4) and evaporated to give crude product which was purified by column chromatography over silica-gel using hexane-ethyl acetate (98:2) as eluent.

General procedure for Raney-Ni dethiomethylation of 2-aryl-3-(methylthio)naphthofurans (7a-b, 12)
A suspension of appropriate methylthiofuran 7a-b or 12 (2 mmol) and Raney-Ni (W2, 0.8 g) in absolute ethanol (25 mL) was refluxed with stirring for 6-7 h (monitored by TLC).The reaction mixture was then cooled, filtered through a sintered funnel and the residue was washed with ethanol.The combined filtrate was evaporated under reduced pressure and the residue was dissolved in chloroform (50 mL), washed with water (2x50 mL), dried (Na2SO4) and evaporated to give crude product which was purified by column chromatography over silica-gel using hexane-ethyl acetate (97:3) as eluent.