Naphthyl vinyl sulfide 5 is prepared by acid-catalyzed addition-dehydration of 2-naphthalenethiol to ethyl acetoacetate. Photocyclization-rearrangement of 5 gives dihydrothiophene 6a, which is desulfurized to 7a; saponification of 7a and polyphosphoric acid cyclodehydration of the resulting acid 7c gives 2-ethyl-l-acenaphthone. A series of 2-thioaryloxyenones lla-k is prepared by reaction of the appropriate aromatic thiol with isophorone epoxide in the presence of base. Photocyclization-rearrangement of 11 gives dihydrothiophenes 12 in high yield; desulfurization of 12 with Raney nickel gives 3-arylcyclohexanones 13, while reductive cleavage of 12 with zinc in acetic acid gives an ortho-substituted benzenethiol isolated in hemithioketal form 14. Thioaryloxyenones 18, 19, 20a, and 20b are prepared from the appropriate thiol and the epoxide derived from 2-cyclopenten-l-one, A1(9)-octal-2-one, and A4(5)cholesten-3-one, respectively; these undergo photocyclization-rearrangement to give dihydrothiophenes. With fused ring thioaryloxyenones 19 and 20 only a cis-decalone ring fusion results; none of the corresponding trans isomer is detected. Acyclic thioaryloxyenones are not available via the epoxy ketone route; 3-thiophenoxy-4-methyl-3-penten-2-one (26) is prepared by reaction of 3-chloro-2,4-pentanedione with thiophenol 'in pyridine to give 3-thiophenoxy-2,4-pentanedione (24), followed by treatment with excess methylmagnesium bromide and finally acetic anhydride at reflux temperature. Irradiation of 26 gives dihydrothiophene 39 in 84% yield. A direct annelation route to 19 involves reaction of thiophenoxymethyl vinyl ketone (44) with the pyrrolidine enamine of cyclohexanone 45. With modification of the annelation reagent, a variety of multicyclic ring systems with angular aromatic substituents should be available by the sequence cycloalkanone annelation-photocyclization-desulfurization. Dihydrothiophene 12a undergoes regioselective alkylation of the equilibrium enolate to give 12b, which is converted to sulfone 46c. Reaction of 46c with 1 N sodium hydroxide gives the ketone cleavage product carboxylic acid 48, demonstrating that highly substituted aryl annelated dihydrothiophene 1,ldioxides are available by methodology based on heteroatom directed photoarylation of aryl vinyl sulfides.W e wish to describe a new aromatic ring substitution process called heteroatom directed photoarylation. T h e methodological term heteroatom directed photoarylation is intended to characterize photochemically initiated, electrocyclic reactions originating from arrangements of a n available electron pair in a heteroatom and the electrons from a t least one aromatic B bond. The synthetic potential of the generalized photoreaction A -B, one example of heteroatom directed pho-B toarylation, will be presented in this report. W e will show that the photoreaction is quite general, proceeds with high chemical and photochemical efficiency, and is compatible with a wide variety of functional groups within the molecular system. O u r studies began...
217 carbon4euterium absorption a t 2200 and 2100 cm-' and carbonyl absorption at 1730 and 1680 cm-' corresponding to the ester and thioester groups. The mass spectrum (70 eV) showed peaks at m/e (relative intensity) 243 (16.6, M+ -SEt), 225 (10, M+ -SEt -H,O), 197 (8, M+ -COSEt -H,O), 87 (100, methyltetrahydrofuryl-d,). The spectrum showed a peak at m/e 86 with intensity 9.3% of that at m/e 87. The second band at Rf 0.49 was removed from the plate and eluted from the silica gel with ether yielding 0.008 g of an oil. The spectral properties of the latter were identical with those of the starting bromide X-d2.Reaction of the Bromide X -d z with Vitamin B12s in H 2 0 with Potassium Carbonate. Hydroxocobalamin (0.090 g, 0.000067 mol) was added to a solution of 0.362 g (0.0026 mol) of anhydrous K&03 in 2 mL of HzO. The resulting suspension was placed under nitrogen and a solution of 0.060 g (0.0016 mol) of NaBH4 in 1 mL of HzO was added. The reaction mixture was stirred at room temperature for 30 min. The reduced vitamin B12s was not dissolved but remained as a dark grey precipitate in a brown colored solution. The reaction mixture was taken into the darkroom and a solution of the 0.080 g (0.00021 mol) of the bromide X-d, in 0.25 mL of absolute methanol was added. The reaction mixture, pH 12.5, was stirred a t room temperature for 24 h. The reaction was extracted with four 25-mL portions of ether, dried over MgS04, filtered, and evaporated. The residue weighing 0.049 g was spotted on a 2-mm silica gel prep plate and developed four times in 24:76 ether-hexane.Band 1 at Rr 0.39 was the rearranged product XVIII-d, weighing 0.029 g (45%). The spectral data (infrared, 250-MHz NMR and deuterium NMR) were identical with those of the rearranged product XVIII-d2 obtained in the reaction in water described above. The mass spectrum showed fragmentation (m/e 243,197, 87) similar to that shown by the rearranged product XVIII-d2. The spectrum showed a peak at mle 86 with intensity 13.7% of that at m/e 87. The m/e 86 peak in the starting bromide VIII-d2 was 8.4% of the m/e 87 peak. Band 2 at R, 0.47 was the unrearranged product XVI-d2 weighing 0.014 g (22%). The spectral data (infrared and nmr) were similar to those of the unrearranged product XVI-d2. The deuterium NMR spectrum showed a single resonance at 6 3.76 corresponding to deuterium a t the carbon adjacent to oxygen on the tetrahydrofuran ring. The mass spectrum showed fragmentation (m/e 243, 225, 197,87) similar to that shown by the unreacted product (64). The spectrum showed the peak at mle 86 with inensity 17.25% of that at mle 87. It appears then that both rearranged and unrearranged products, XVIII-d2 and XIX-d,, are undergoing exchange, to a limited degree, at the position a to oxygen on the tetrahydrofuran ring.Control Reaction without Hydroxocobalamin. A solution of 30 mg (0.8 mmol) of sodium borohydride in 0.5 mL of DzO was added to a solution of 181 mg (1.3 mmol) of anhydrous potassium carbonate in 1 mL of D20. This solution was then treated with 40 mg (0.1 mmol) of...
References and Notes(1) (a) Fellow of the Alfred P. Sloan Foundation; (b) University Fellow, Rutgers University.
The tetracyclic structural analogue (7) of morphine is prepared in high yield by photocyclizationrearrangement of the aryloxyenone (4).WE describe our approach towards a total synthesis of morphine (la) and codeine (lb). The key step involves
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