摘要:

J. CHEM. soc. PERKIN TRANS. 1 1993 2317 Isolation of Episulfones from the Ramberg-Backlund Rearrangement. Part 2.t X-Ray Molecular Structure of 2,3-Epithio-8.8-dimethyl-6,I 0-dioxaspi ro[4.5] -decane S,S-Dioxide and of r-6-Benzyl-t-7,t-8-epithio-l,4-dioxaspiro[4.4]nonane S,S-Dioxide Stephen M. Jeffery, Alan G. Sutherland, Simon M. Pyke, Aanne K. Powell and Richard J. K. Taylor*#$ School of Chemical Sciences, University of East Anglia, Norwich, NR4 7TJ, UK 5~ ~ 5 5~~5 ~~~ ~ For the first time, episulfones have been isolated by the treatment of x-halogeno sulfones with base under the conditions of the Ramberg-Backlund reaction. 3,3-Dialkoxy-6-thiabicyclo[3.1.O]hexane dioxides 3a-c and Ila, b have been fully characterised, X-ray crystal structures having been obtained for compounds 3c and Ila.Attempts to prepare episulfones with substituents at the bridgehead position were unsuccessful, however. The thermal stabilities of some of these episulfones have been studied, as have their reactions with base. The Ramberg-Backlund rearrangement, the base-mediated conversion of an a-halogeno sulfone into a regio-defined alkene, has attracted considerable synthetic and mechanistic interest since its discovery in 1940.'~~ in which a-Meyers' m~dification,~ chlorination and in situ Ramberg-Backlund rearrangement are achieved by direct treatment of the sulfone with KOH-CC1,- Bu'OH, further extended the versatility of the process. Other recent innovations include the development of the Michael- induced Ramberg-Backlund rearrangement,4 the use of sulfinyl leaving groups 557 and the introduction of a-trifluoromethyl- sulfonyl dimet hyl sulfone and a-halogenoalkanesulfonyl bromides as novel Ramberg-Backlund precursors.The enduring utility of the Ramberg-Backlund rearrangement is demonstrated by recent applications to the synthesis of natural and novel cycl~pentenes,~.~*~.' strained bicyclic alkenes,'.' ' enediynes related to esperamicin,' calicheamicin and neo- carzinostatin,I3 and (+)-eremantholide A.14 Detailed mechanistic studies have been carried out to establish the mechanism of the Ramberg-Backlund rearrange- ment as that shown in eqn. (l).29''*'6 Although episulfones (thiirane 1,l -dioxides) have not previously been observed from this sequence, indirect support for their intermediacy has been obtained by taking authentic episulfones, prepared by other rnethod~,'~and showing that they give alkenes under the conditions normally employed for the Ramberg-Backlund re- action.I6 In addition, thiirene 1,l-dioxides have been obtained from a,a-dihalogeno sulfones by treatment with base.I8 We now report the first examples of episulfones obtained by the treatment of a-halogeno sulfones with base.This discovery was made possible by the facile Ramberg-Backlund rearrange- ment of a-iodothiane dioxides we report recently." Scheme 1 illustrates studies carried out on unsubstituted thian-4-one ketals. Treatment of the readily available 2,3-di- hydrothiin-4-one 1 2o with trimethylsilyl iodide followed by in situ quenching2' with ethylene glycol, butan-1-01 or 2,2-dimethylpropane-l,3-diolgave P-iodo acetals 2a-c (X = I) in high yield.The bromo and chloro analogues of compound 2c -f For Part 1, see ref. 19. $ Present address: Department of Chemistry, University of York, Heslington, York YO1 5DD, UK. Table 1 Yields for the preparation of compounds 24 (%) R,R 1-2 2-3 2-4 3-4 a CH,CH, X = I,88 87 a a b Bu X = I,84 82 93 91 c CH,C(Me),CH, X = I, 85 85 91 93 X = Br, 56 74 X = C1, 14 85 (I Yield difficult to estimate due to volatility of product. were also prepared, albeit in lower yield, by the use of trimethylsilyl bromide or chloride. The halogen atom adopts an equatorial position in all of the adducts 2 and so should be ideally positioned for 1,3-e1imination.This orientation was established by 'H NMR spectroscopy in which the geminal methine protons exhibit clear axial-axial coupling (J 13.3-13.6 Hz for iodides, 12.8 Hz for the bromide and 12.3 Hz for the chloride), and so should be ideally positioned for 1,3-elimination. Attempts to study the Ramberg-Backlund rearrangement of iododioxolane 2a were hampered by its poor solubility in tetrahydrofuran (THF) at low temperature. With an excess of potassium tert-butoxide in THF at -78 "C to room temperature the cyclopentene 4a 22 was formed as expected. The yield of compound 4a was difficult to estimate due to its volatility but it was readily identified by 'H and I3C NMR spectroscopy and by high-resolution mass spectroscopy. When a mixture of THF and dimethyl sulfoxide (DMSO) at 0 "C were used as solvent for this reaction, however, 7,8-epithio-1,4- dioxospiro[4.4]nonane S,S-dioxide 3a was obtained in 87% yield as a cream-coloured solid, m.p. 148-1 50 "C (decomp.) which was fully characterised.Solubility problems and in- adequate control over reaction temperature rendered this reaction somewhat capricious. Therefore ketals 2b, c were investigated in an attempt to improve solubility in THF and thus make the transformation more reliable. This approach was successful as both compounds underwent smooth conversion into the corresponding episulfones 3b, c in high, reproducible yield at -78 "C (Table 1). The dibutyl ketal3b is a viscous oil but the dioxane 3c is a crystalline solid, with a sharp m.p.(94.0- 2a-c 3a-c iv v RO OR& 4a-c Scheme 1 Reagents and conditions: i, Me,SiX, MeCN; ii, ROH; iii, KOBu', THF-DMSO, 0 "C or KOBu', THF, -78 "C; iv, KOBu' Table 2 Thermal decomposition of episulfones 3" 3 Remaining (%) Time (tldays) 3b 3c 0.7 87 95 1.7 78 90 2.8 70 85 3.75 63 81 6.7 46 71 9.7 b 64 ~____________ ~ a Determined by 'H NMR spectroscopy in CDC1, at -30 "C. Not measured. 95.0°C), and so was used for an X-ray crystal-structure determination (see later). It should be noted that this simple conversion of a-halogeno sulfone into episulfone is not dependent on the presence of an iodide leaving group: the a-bromo and a-chloro sulfones 2c (X= Br, Cl) also gave compound 3c in high yield on treatment with potassium tert- butoxide at low temperature.On treatment with base, episulfones 3b, c underwent efficient conversion into the corresponding cyclopentenes 4b and 4q2 which were also prepared directly by conventional Ramberg-Backlund re-arrangement of iodo sulfones 2b,c using an excess of base. All of the episulfones 3could be kept at -20 "C for several months without the occurrence of significant decomposition. Even at room temperature, decomposition to cyclopentenes 4 was relatively slow, as can be seen from Table 2. The crystalline episulfone 3c has a half-life of ca. 15 days in CDC1, solution at room temperature. Alkyl-substituted thianes were also studied, as shown in Scheme 2.The requisite 2- and 3-substituted dihydrothiin-4- ones 8and 14were prepared by modifying methods previously developed in these laboratories. '0,24 Thus, conjugate reduction of the thiin-4-one 5 lo to give ally1 3,4-dihydro-4-0~0-2H-thiine-3-carboxylate 6, followed by alkylation and palladium-catalysed decarboxyallylation 24925 of the adducts 7a, b provided access to the 3-substituted sulfides 8a, b. Conjugate addition to compound 6readily afforded the P-keto esters 13a, b," which were decarboxyallylated to the sulfides 14a, b using magnesium chloride in refluxing aq. dimethylformamide (DMF).26 Tetrakis(triphenylphosphine)palladium(o) and mor- pholine can also be employed for the decarboxyallylation of compounds 13 but is less efficient (e.g., 14a was obtained in 9 1 % using MgCl, and 58% using PdO).Oxidation of sulfides 8and 14to the corresponding sulfones 9 and 15 was achieved in high yield with OXONE@ J. CHEM. SOC. PERKIN TRANS. 1 1993 (2KHS0,-KHS04-K2S04) in aq. methanol 27 and these compounds, in turn, were converted into P-iodo ketals 10 and 16 by the use of Me,SiI-ethylene glycol, as before. The 3-substituted systems 10were obtained as single diastereoisomers ( >95%) which were assigned the trans-configuration by 400 MHz 'H NMR spectroscopy. The 2-benzyl compound 16b was predominantly the cis-isomer (cis :trans -96 :4) but, surpris- ingly, the 2-butyl sulfone 16a was isolated as a 3 :1 cis: trans diastereoisomeric mixture from which pure cis-isomer could be obtained by recrystallisation.* Analysis by 400 MHz 'H NMR spectroscopy (e.g.Fig. 1 for 16a)indicated that all of these iodo ketals appear to have iodine as the equatorial substituent. Given the reported 28 conformational free-energy differences of iodine (AGO -0.4 kcal mol-') t and ethyl (AGO -1.8 kcal mol-') in cyclohexane derivatives, this observation indicates that there is an electronic/dipolar preference for equatorial halogen in these thiane dioxide systems which appears to override the usual equatorial preference of the alkyl substituents. It should be noted that the halogen substituents, when equatorial, are disposed within the internal bisector of the sulfonyl oxygen atoms. It is possible, however, that trans-16a exists in a twist- chair conformation; the consistent shielding of all ring carbon resonances in the I3C NMR spectrum of trans-16acompared with the corresponding cis-isomer lends credence to this sugges- tion.Treatment of compounds 10a, b with potassium tert-butoxide in THF at -78 "C efficiently produced the corresponding episulfones lla, b, indicating that alkyl substitution P to the sulfonyl group does not preclude episulfone formation. In the case of compound lob, the reaction mixture was allowed to warm to room temperature and the episulfone llb was isolated in 65% yield together with the corresponding cyclopentene 12b.7 A similar result (lla,69% + 12a,7 28%) was observed when the reaction of sulfone 10a was allowed to warm to room temperat~re,'~but when the reaction was quenched at -78 "C the episulfone lla was produced almost exclusively (90%). In order to optimise episulfone formation, quenching the re- action at -78 "C is obviously important.Again, the use of higher reaction temperatures gave efficient Ramberg-Backlund rearrangement of iodo sulfones 10a, b directly into the expected cycloalkenes 12a, b. In addition, episulfone lla was efficiently converted into the cyclopentene 12a on heating to its m.p. or by treatment with base. Episulfone lla can be stored as a solid at -18 "C without noticeable decomposition (< 5%) over a 2 month period, whereas storage in solution at room temperature leads to significant decomposition to the cyclopentene 12a ( -66% conversion after 28 days according to 'H NMR spectros- COPY).By contrast with the P-substituted substrates, the a-sub- stituted compounds 16a, b did not produce episulfones although their Ramberg-Backlund rearrangements to cyclopentenes occurred efficiently.The resulting cyclopentene ketals 17a, b proved to be surprisingly labile on silica gel chromatography. In the rearrangement of the a-butyl compound 16a the only product isolated after chromatography was the known 30 3-butylcyclopent-2-enone 18a (86%).* In the case of the a-benzyl analogue 16b, the expected cyclopentene ketal 17b (62%) was accompanied by 3-benzylcyclopent-2-enone 18b31 as a minor (29%) by-product. Failure to isolate episulfones from the a-iodo sulfones 16a, b (and from closely related m,P-disubstituted thiane dioxides) * The use of Me,SiBr in this reaction also produced a diastereoisomeric mixture (cis:trans 6 :5) of adducts 16a (I = Br) with bromine equatorial according to 'H NMR spectroscopy.This mixture underwent smooth Ramberg-Backlund rearrangement-hydrolysis to give compound 18a in quantitative yield. t 1 cal = 4.184 J. J. CHEM. SOC. PERKIN TRANS. I 1993 0 0 @CO~CH~CH=CH~ -fiC02C H2CH= CH, c i ii s, 5 6 7a; R =PhCH, 8a; R = PhCH, b; R = CH2CH=CH2 b; R = CH2CH=CH2 IV 13a; R=Bu 14a; R =Bu b; R = PhCH, b; R = PhCH2 n 02 9a; R = PhCH, b; R = CH2CH=CH2 S n 02 lla; R = PhCH, b; 1 17a; R=Bu R vii b; R = PhCH2 Oho xiii ~ t II 02 I' 15a; R= Bu 16a; R=Bu 02 10a; R = PhCH, 4,b; PhCH, b; R = PhCH, b; R = CH2CH=CH2 18a; R= Bu 12a; R = PhCH, b; R=PhCH, b; R = CHzCH=CH2 Scheme 2 Reagents and conditions: i, NaBH,, THF (67%);ii, RBr, K2C03,acetone (7a,92%;7b,85%);iii, Pd(PPh,),-morpholine, THF (8a,83%; 8b,74%);iv, OXONE, aq.MeOH (9a,94%;9b,50%); v, Me,SiI, MeCN; then HOCH,CH,OH (lOa,93%;lob, 96%);vi, KOBd, THF, -78 "C(1 la, 90%;llb,65% + 12b,20%); vii, KOBu', THF, room temp. (12a,85%;12b,87%);viii, On lla only: KOBu', THF, room temp. (93%)or 110 "C, 20 min (88%);ix, RMgBr + catalyticCuBroSMe,; x, MgCI2-6H,O,aq. DMF, reflux (14a,75%from 5;14b,43%from 5);xi, as iv (15a,91%;15b,87%); xii, as v [16a, 90% (cis:trans 3 :1); 16b, 84% (cis)];xiii, KOBu', THF, -78 "C; then SiOz chromatography (16a-Ma, 86%; 16b--+ 17b, 62% + 18b, 29%) 40 42S 5.01 6 5.11(dd, J13.8 (dd, J 10.8 ------ij>uand 4.0 Hz) and 4.2 Hz)I s Bu s He cis -1 6a trans -1 6a Fig.1 suggests that the rate of loss of sulfur dioxide (either thermally or in a base-promoted process) from trisubstituted episulfones is fast compared with the disubstituted examples 3a-c and lla, b, allowing isolation of the latter compounds from the basic reaction media. It should be noted that a-iodo sulfone 16a, as a 3 :1 cis: trans mixture (see Fig. l), afforded the expected Ramberg-Backlund reaction product in 86%yield, indicating that the disposition of the alkyl substituent has little bearing on the outcome of the reaction.However, the use of half a mole equivalent of base in this reaction led to isolation of compound 18a (42%) together *Full details of structures 3c and lla have been deposited at the Cambridge Crystallographic Data Centre. See 'Instructions for Authors,' in the January issue. with the cis-disubstituted starting material 16a (46%). This result indicates that trans-l6a, which possesses the favoured W-plan arrangement,2 reacts at a faster rate than the cis-diastereoisomer, which presumably undergoes equilibration prior to formation of episulfone. Structural Studies.*-The structures of compounds 3c and lla have been confirmed by X-ray crystallographic analysis (see Fig. 2 and Tables 3 and 4).* Table 4 lists selected bond lengths.The X-ray crystal structures of compounds 3c and lla were solved by Direct Methods using SHELXTL PLUS. Neutral-atom scattering factors (including anomalous scattering) were used.32All non-H atoms were refined with anisotropic thermal parameters. The hydrogen atoms were readily located from AF maps and their positions refined in successive cycles of least squares using fixed isotropic thermal parameters. Crystals of J. CHEM. SOC. PERKIN TRANS. 1 1993 Table 3 Crystallographic data Compound 3c lla Formula CIOHl 6°4s C14H 16°4s Formula wt. 232.3 280.3 Temp. (T/K) 293 293 Crystal system Triclinic Monoclinic Space group PT %In a (4 5.635(6) 6.061(3) b (A) 5.913(6) 14.71 8(5) c (4 18.180(15) 15.363(4) a(deg) 89.48(7) 90 P (deg) 88.59( 8) 95.32(3) Y (deg) 68.22( 8) 90 z 2 4 F(OO0) 248 592 Dcalc (g Cm-3) 1.37 1.36 Crystal dimensions (mm) 0.18 x 0.20 x 0.30 0.20 x 0.22 x 0.24 Radiation Mo-Ka (A0.7107 A) Mo-Ka Monochromator graphite graphite P (mm-') 0.267 0.233 Scan type 0 0 28 range (deg) 247 2-50 Indices collected +h, kk,+I +h, +k, _+I Reflections collected 1685 2695 Independent 1487 2334 Observed 956 [F > 6o(F)] 1729 [F > 4o(F)] Scan speed (deg min-') 2-15.63 1.5-14.65 No.of L.S. parameters 131 220 Datalparam. 7.3 7.86 R" 14.05 9.66 Rw " 12.45 8.74 g" 0.004 0.0001 Min./max. e density (e k3) -0.9811.63 -0.6310.56 period of data collection. The high R-values obtained for both compounds are further evidence of their instability. The crystal structure of (2)-2-but-2-ene episulfone has been reported33 as has the microwave spectrum of ethylene episulfone.34 These studies draw particular attention to the unusually long carbon-carbon bond length of episulfones at -1.6 A.Similar C-C bond lengths are observed for episulfones 3c and lla [3c: 1.546(16) A; lla: 1.655(10) A] although, even allowing for the low accuracy of the structure determinations, the significantly shorter C-C bond length in compound 3c, compared with the benzylated analogue lla, is noteworthy. Concluding Remarks.-Episulfones have been isolated by the treatment of a-halogeno sulfones with base under the conditions of the Ramberg-Backlund reaction. Episulfones 3a-c and 1la, b have been fully characterised, X-ray crystal structures having been obtained for compounds 3c and lla.Further work, c(,,) including modification of ring size, ketal moiety, and substituent pattern, is in progress to evaluate the reasons for the stability of these novel episulfones and to obtain information concerning the mechanism of episulfone decomposition. The high stability and synthetic accessibility of the episulfones indicates that they might have synthetic potential in their own right. This area is also under current investigation. Experimental 'H NMR spectra (6,) were recorded using JEOL PMX 60, JEOL EX 90 and JEOL GSX 400 spectrometers and were assigned by use of either homonuclear decoupling or COSY-45 experiments at 400 MHz. 13C NMR spectra (6,) were Fig.2 ORTEP view of episulfones 3c and lla with numbering system recorded using JEOL EX 90 and JEOL GSX 400 spectrometers used in the tables of data (22.5 and 100 MHz respectively) and were assigned by use of either DEPT or heteronuclear correlation experiments at 100 compound 3c were particularly unstable to X-ray bombardment MHz. Samples were prepared as solutions in CDC1, containing at ambient temperature and decomposed by -15% over the tetramethylsilane as internal standard. J-Values are given in Hz. J. CHEM. SOC. PERKIN TRANS. I 1993 Table 4 Selected bond lengths (A) (a)Compound 3c Wto(1) 1.464(9) 1.436( 13) W)-C(l) 1.713(15) 1.705(15) 0(3W(4) 1.444(18) 1.439( 16) 0(4)-C(4) 1.386(20) 1.430( 14) C(I jC(2) 1.546( 16) 1.541(1 6) C(2)-C( 3) 1.551( 18) 1.570(I 8) C(4)-C(5) 1.520( 16) 1.54 l(22) C(7)-C(8) 1.481(25) 1.5 16( 18) C(7)-C(10) 1.559(19) (b)Compound lla 1.437(7) 1.414(7) 1.747(7) 1.741(9) 1.402(9) 1.417( 13) 1.394(10) 1.418( 13) 1.655(10) 1.504(9) I .475( 12) 1.576(9)1.544( 11) 1.559(9) I .405( 16) 1.500(11)1.357( 12) 1.359( 12) 1.400( 14) 1.349(16) 1.350( 16) 1.422( 15) IR spectra (vmaJ were recorded on a Perkin-Elmer FT IR 1720X spectrophotometer as CHCl, solutions or mulls (Nujol) for solid samples and as thin films for liquid samples.Mass spectra were recorded on Kratos MS 25 (low resolution) or Kratos VG Zab-E (high resolution) instruments. Light petroleum refers to the fraction of boiling range 40-60 OC, which was redistilled before use.DMSO was stored over 4 A sieves, THF was dried over sodium/benzophenone ketyl and distilled immediately before use, acetonitrile was distilled from calcium hydride, and morpholine from sodium before use. 2,3-Dihydro- thiin-4-one 1,l -dioxide l,,' allyl 4-0~0-4H-thiine-3-carboxylate 5,lo and tetrakis(tripheny1phosphine)palladium were pre- pared using literature procedures; other starting materials were used as received. Analytical TLC was performed on Merck 5554 aluminium-backed silica gel plates. A standard work-up refers to 2/3 extractions with the specified solvent, washing of the combined extracts with water, drying (MgSO,) and removal of the solvent on a rotary evaporator. Column chromato- graphy was carried out under gravity, using silica gel (Sorbsil C 60-H).Preparative centrifugal chromatography was carried out on a Chromatotron Model 7924T using silica gel plates (Merck 7749). M.p.s were recorded on a Kofler hot-stage m.p. apparatus and are uncorrected. Temperatures given for Kugelrohr distillations refer to the oven temperatures. (a) Preparation of Novel Su@des.-Ally1 3,4-dihydr0-4-0~0-2H-thiine-3-carboxylate 6.A solution of sodium borohydride (0.226 g, 5.97 mmol) in dry THF (450 cm3) was added dropwise over a period of 2 h to a solution of allyl 4-0x0-4H-thiine-3- carboxylate 5 (1.17 g, 5.96 mmol) in dry THF (25 cm3) at 0 "C. When the addition was complete the solution was stirred for a further 15 min prior to quenching with aq.ammonium chloride (50 cm3). The two-phase mixture was stirred for 30 min and then was diluted with diethyl ether (400 cm3) and water (100 cm3). A standard ethereal work-up, followed by preparative centrifugal chromatography [CH,CI,-ethyl acetate (9 : l)] gave the title compound6(0.79 g, 67%) as a bright yellow oily mixture of keto and enol tautomers (85 : 15) (Found: C, 54.7; H, 5.3. C9H1,O3S requires C, 54.53; H, 5.08%); Rf0.31 [CH,Cl,-ethyl acetate (9:l)]; vma,(film)/cm-' 3454 (OH, enol), 1743 (M,ester) and 1630 (M,keto); 6,(400 MHz) keto form: 3.34 (1 H, ddd, J2ax.2eq -l3-2,J2eq,3ax 3*7,J2eq,6eq lml, 2-Heq), 3*61(l H, dd, J2ax,Zeq -13-29J2ax,3ax 10.6, 2-Hax), 3.69 (1 H, dd, J2ax,3ax 10.6, J2eq,3ax 3.7, 3-Ha,), 4.654.74 (2 H, m, OCH,), 5.25 (1 H, ddt, 2321 Jcis 10.3, Jgem 1-594Jallylic 1-57 CHXHH), 5.35 (1 H, ddt, Jtrans 17.2, Jgem 1.5, 4Jallylic1.5,CH-CHH), 5.92 (1 H, ddt, Jcis10.3, Jrra, 17.2, Jvk 5.9, CH=CH,), 6.23 (1 H, d, J5.6 10.3, 5-H) and 7.48 (1 H, dd, J2cq.6 1.1,J5,610.3,6-H); en01 form: 3.71 (2 H, m, 2-H2), 4.65-4.74 (2 H, m, OCH,), 5.27 (1 H, ddt, Jct10.3, Jgem 1.5, 4Jallylic 17.2, Jgem1.5, CH=CHH), 5.35 (1 H, ddt, Jtrons 1.5, 4Jallylic 1-53 CHeHH), 5.92 (1 H, ddt, Jck 10,3Jrrans 5.9,17.2,Jvic C~~Hz),5.97(1H,d,J5,610.3,5-H),6.92(1H,brd,J5,610.3, 6-H) and 12.13 (1 H, s, OH); &(lo0 MHz) keto form: 29.04 (C-2), 51.83 (C-3), 65.87 (OCHZ), 118.43 (CH=CH2), 123.08 (C-5), 131.31 (CHZH,), 146.10 (C-6), 167.82 (0,ester) and 188.36 (C-4); enol form: 23.48 (C-2), 65.00 (OCH,), 85.86 (C-3), 118.17 (CH=CH,), 119.44 (C-5), 131.79 (CHSH,), 137.72 (C-6), 166.41 (GO, ester)and 171.44(C-4); m/z 198 (21%, M'), 157 (22, M -CHZCHSH,), 113 (100,157 -COZ).3-Benzyl-2,3-dihydro-4H-thiin4one8a. (i) A solution of the dihydrothiinone 6 (0.53 g, 2.61 mmol) in dry acetone (15 cm3) was treated with benzyl bromide (0.38 an3,0.55 g, 3.22 mmol), then anhydrous potassium carbonate (1.1 1 g, 8.03 mmol) was added under nitrogen to the stirred mixture. The mixture was stirred for 24 h at room temp., then was concentrated at reduced pressure. The residue was taken up in water (30 cm') and CH,Cl, (30 cm3) and subjected to a standard CH,Cl, work-up incorporating a brine wash. The crude material was purified by preparative centrifugal chromatography with CH2C12 as eluent to give allyl 3-benzy1-3,4-dihydro-4-0~0-2H-thiine-3-carboxylate 7a (0.71 g, 92%) as a yellow oil which was fully characterised.(ii) A solution of ester 7a (1.83 g, 6.35 -01) in dry THF (60 an3)under nitrogen was treated with morpholine (5.53 g, 60.35 -01) and tetrakis(triphenylphosphine)palladium(o) (0.37 g, 0.32 mmol). The mixture was stirred at room temp. for 3 h, then at 40°C for 30 min. After cooling, the reaction mixture was filtered through Celite, then the solvent was removed. The crude material was purified by preparative centrifugal chromato- graphy [diethyl ether-light petroleum (2 : 3)J to give the title compound8a (1.08 g, 83%) as a pale yellow oil (Found: C, 70.5; H, 5.9.C,,H,,OS requires C, 70.55; H, 5.92%); R,0.46 [diethyl ether-light petroleum (2 : 3)]; ~,~,(CHCl,)/crn-~ 1665 (0); bH(400 MHz) 2.69-2.87 (3 H, m, 2-Ha,, 3-Ha, and CHHPh), 3.12 (l H, ddd, J2ax,2eq -13'3,J2eq.3eq 2.8, J2eq.6 O.9, 2-Heq), 3.22 (1 H, dd, Jgem-12.3, Jvic2.5, CHHPh), 6.16 (1 H, d, J5.6 10.1, 5-H), 7.20-7.25 (3 H, m, 2'-, 4'-, 6'-H), 7.28-7.32 (2 H, m, 3'-, 5'-H) and 7.39 (1 H, dt, J2.6 0.9, J5,610.1, 3-H); Jc(l0O MHz) 30.26 (C-2), 33.82 (CHZPh), 46.73 (C-3), 122.83 (C-5), 126.36 (C-4'), 128.39 (C-3', -5'), 128.88 (C-2', -6'), 138.15 (C-1'), 145.38 (C-6) and 194.96 (C-4); m/z 204 (91%, M+). 3-AZZyZ-2,3-dihydro-4H-thiin-4-one8b. The procedure (i) above was carried out using potassium carbonate (3.317 g, 24.0 mmol), compound 6 (1.586 g, 8.0 mmol), allyl bromide (1.161 g, 9.6 mmol) and dry acetone (32 an3)at room temp.for 20 h. Work-up as before, followed by column chromatography [ethyl acetate-light petroleum (1 : 4)], gave allyl 3-allyl-3,4-dihydro-4- oxo-2H-thiine-3-carboxylate7b (1.624 g, 85%) as a yellow oil which was fully characterised. The procedure (ii) above was followed using morpholine (0.653 g, 7.50 mmol), te trakis(triphenylphosphine)palladium(o) (0.043 g, 0.75 mmol), ester 7b(0.179 g, 0.75 mmol) and dry THF (7.5 cm3)at room temp. for 40 h. The reaction mixture was then filtered through a short column [diethyl ether-light petroleum (2 : 3) J, then was further purified by column chromatography [diethyl ether-light petroleum (2: 3)J to give the title compound 8b (0.086 g, 74%) as a yellow oil (Found: C, 62.7; H, 6.7.C,HloOS requires C, 62.30; H, 6.54%); Rf 0.62 [ethyl acetate- toluene (3: 17)J; vm,,(CDCl,)/cm-' 1660 (GO)and 1550 (W);bH(6O MHz) 2.08-3.50 (5 H, m, 1'-and 2-H, and 3-H), 4.90-5.32 (2 H, m, 3'-H,), 5.46-5.95 (1 H, m, 2'-H), 6.12 (1 H, d, J5,610.8, 5-H) and 7.38 (1 H, d, J5,610.8, 6-H); 6,(22.5 MHz) 31.O and 32.6 (C-1' and -2), 44.8 (C-3), 118.0 (C-3'), 123.3 (C-5), 135.0 (C-27, 145.5 (C-6) and 195.3 (C-4); m/z 154 (8%, M+). 2-Butyl-2,3-dihydro-4H-thiin-4-one14a. (i) A solution of copper(1) bromide-dimethyl sulfide complex (0.21 g, 1.02 mmol) in dry dimethyl sulfide (5 cm3) was added dropwise to a stirred solution of butylmagnesium bromide [prepared from butyl bromide (4.90 cm3, 6.25 g, 45.63 mmol) and magnesium turnings (1.14 g, 46.89 mmol)] in dry THF (1 00 cm3) at -78 "C under nitrogen. The mixture was stirred for 2 h, then a solution of allyl 4-oxo-4H-thiine-3-carboxylate (5.44 g, 27.72 mmol) in dry THF (85 cm3) was added dropwise over a period of 30 min.The mixture was stirred for 1.5 h, then saturated aq. ammonium chloride (150 cm3) was added. The mixture was warmed to room temp., then was diluted with water (50 cm3) and subjected to a standard ethereal work-up incorporating a brine wash. Column chromatography [light petroleum-diethyl ether (9 : l)] gave allyl 2-butyl-3,4-dihydro-4-oxo-2H-thiine-3-carboxylate 13a (5.82 g, 82%) as a yellow oily mixture of keto and enol tautomers (1 :2), R,0.80 [CH,Cl,-ethyl acetate (4: l)], which gave consistent IR, 'H NMR and MS data.J. CHEM. SOC. PERKIN TRANS. 1 1993 (C-3', -5'), 129.13 (C-2', -6'), 136.73 (C-1'), 145.46 (C-6) and 194.12 (C-4); m/z 204 (48%, M'). (b) General Procedure for Preparation of Sulfones from Su@des.-A solution of OXONE@ in water was added to a stirred solution of the sulfide in methanol at 0 "C. The mixture was stirred for 6 h-2 days at room temp., and the reaction mixture was diluted with water and was then subjected to a standard CH,Cl, work-up. 3-Benzyl-2,3-dihydro-4H-thiin-4-one1,l-dioxide 9a. A solu- tion of the sulfide 8a (1.08 g, 5.29 mmol) was treated with methanol (30 cm3), OXONE@ (3.28 g, 5.34 mmol) and water (30 cm3) for 6 h as described above to give the title compound9a (1.18 g, 94%) as a solid, m.p.142-144 "C (Found: C, 60.8; H, 5.1. C,,H,,O,S requires C, 61.00; H, 5.12%); R,0.25 (CH,Cl,); vmax(CHC13)/cm-' 1700 (CLO), 1334 (SO,, asym) and 1136 (SO,, sym); 6,(400 MHz) 2.79 (1 H, dd, Jgem-14.3, Jvic9.2, CHHPh), 3.31 (1 H, dd, J2ax,2eq -14.0,J2ax,3ax 11.6, 2-Ha,), 3.36 (l H, ddd, J2ax,2ax -l4a0, J2eq,3ax 4.6, J2eq,6 3*1, 2-Heq), 3*38 (1 H, dd, Jgem-14.3,Jvic4.3, CHHPh), 3.50 (1 H, dddd, J2ax,3ax (ii) Ally1 2-butyl-3,4-dihydro-4-oxo-2H-thiine-3-carboxylate11.6,J2eq,3ax 4.6, Juic9.2, Joic4.3, 3-Ha,), 6.40 (1 H, d, J5,6 11.3, 13a (2.46 g, 9.67 mmol) and magnesium chloride hexahydrate (3.67 g, 18.06 mmol) in DMF (100 cm3)-water (10 cm3) were heated at reflux for 20 h. The reaction mixture was diluted with water (250 cm3) and subjected to a standard ethereal work-up incorporating a brine wash.Column chromatography [light petroleum-diethyl ether (2 : l)] gave the title compound 14a (1.51 g, 91%) as a yellow oil (Found: C, 63.8; H, 8.5; S, 18.5. C,H,,OS requires C, 63.49; H, 8.29; S, 18.83%);Rf0.22 [light 5-H), 7.12 (1 H, dd, J2eq,63.1, J5,611.3,6-H) and 7.15-7.35 (5 H, m, Ph); 6,(100 MHz) 34.24 (CH,Ph), 46.53 (C-3), 53.03 (C-2), 127.23 (C-4'), 128.96 (C-3', -57, 129.16 (C-2', -6'), 132.44 (C-5), 136.19 (C-l'), 142.17 (C-6) and 193.17 (C-4); m/z236 (8%, M+). 3-Allyl-2,3-dihydro-4H-thiin-4-one1,l-dioxide 9b. 3-Allyl-2,3-dihydro-4H-thiin-4-one 8b (0.580 g, 3.76 mmol) was treated with methanol (15 cm'), OXONE@ (3.467, g, 5.64 mmol) and water (1 5 cm3) for 21 h as described above.Column chromato- petroleum-ethyl acetate (19 : l)]; v,,,(filrn)/cm-' 1663 (M);graphy with CH,C1, as eluent gave the title compound 9b 6,(400 MHz) 0.86 (3 H, t, J,,,,, 7.3, 4'-H,), 1.24-1.40 (4 H, m, 2'-, 3'-H,), 1.59-1.71 (2H,m, 1'-H,), 2.53 (1 H, dd, J2ax,3ax11.9, J3ax,3eq -16-33 3-Hax), 2-72 (1 H, dd, J2ax,3eq 3-33J3ax,3eq -16-39 3-He,), 3.41-3.48 (1 H, m, 2-H), 6.10 (1 H, d, J5,610.1,5-H) and 7.39 (1 H, d, J5.6 10.1 6-H); 6,(1OO MHz) 13.83 (C-4'), 22.29 (C-3'), 28.67 (C-2'),33.64 (C-1'), 43.05 (C-2), 44.84 (C-3), 123.29 (C-5), 145.80 (C-6) and 194.61 (C-4); m/z 170 (30%, M') and 113 (19, M+ -C,H,). 2-Benzyl-2,3-dihydro-4H-thiin-4-one14b. (i) The procedure above was followed using copper(1) bromide-dimethyl sulfide complex (0.12 g, 0.58 mmol), dry dimethyl sulfide (3 cm3) and benzylmagnesium chloride (12 cm3 of a 2.0 mol dmp3 solution in THF, 24.00 mmol) in dry THF (60 cm3), a solution of the ester 5 (4.05 g, 20.64 mmol) in dry THF (70 cm3) being added dropwise during 60 min.The mixture was stirred for 25 min, saturated aq. ammonium chloride (90 cm3) was added, and the reaction mixture was processed as above. The crude material was partially purified by column chromatography with CH,Cl, (0.353 g, 50%) as a solid, m.p. 53.0-55.5 "C (Found: C, 51.8; H, 5.5. C,H,,O,S requires C, 51.60; H, 5.41%); R,0.43 (CH,Cl,); vmax(CDCl,)/cmp' 1695 (M),1330 (SO,, asymmetric) and 1135 (SO2, symmetric); 6,(60 MHz) 2.31-2.99 (2 H, m, 1'-H), 3.24-3.69 (3 H, m, 2-H, and 3-H), 4.95-6.13 (3 H, m, 2'-H and 3'-H,), 6.38 (1 H, d, J5,611.4, 5-H) and 7.16 (1 H, dd, J2eq,6 2.4, J5.6 11.4 6-H); ac(22.5 MHz) 32.8 (C-If), 44.5 (C-3), 53.6 (C-2), 119.9 (C-3'), 132.5 and 132.8 (C-2' and -5), 142.3 (C-6) and 193.1 (C-4); m/z 186 (4%, M').2-Butyl-2,3-dihydro-4H-thiin-4-one1,l-dioxide 15a. 2-Butyl-2,3-dihydro-4H-thiin-4-one 14a (0.60 g, 3.52 mmol) was treated with methanol (30 cm3), OXONE@ (3.25 g, 5.29 mmol) and water (30 cm3) for 2 days as described above. Preparative centrifugal chromatography [light petroleum-ethyl acetate (13 : 7)] gave the title compound 15a (0.65 g, 91%) as a crystalline solid, m.p. 44-46 "C(Found: C, 53.6; H, 7.1; S, 15.6. C,H,,O,S requires C, 53.44; H, 6.98; S, 15.85%);R,0.40 [light petroleum- ethyl acetate (7 : 3)]; vma,(Nujol)/cm-' 1685 (M),1308 (SO,, as eluent to give allyl 2-benzyl-3,4-dihydro-4-0~0-2H-thiine-3-asym) and 1142 (SO,, sym); 6,(400 MHz) 0.99 (3 H, t, J3,,,, carboxylate 13b (2.58 g) as an orange oily mixture of keto and enol tautomers (1 : l), R, 0.56 [light petroleum+thyl acetate (3 :2)], which gave consistent IR, 'H NMR and MS data.(ii) Conjugate adduct 13b (1.60 g), magnesium chloride (1.35 g, 14.18 mmol) and pH 7.2 aq. phosphate buffer (ex-Aldrich; 5 cm3) in DMF (60 cm3) were heated at reflux for 16 h under nitrogen. The reaction mixture was diluted with water (1 50 cm3) and subjected to a standard ethereal work-up incorporating a brine wash.Preparative centrifugal chromatography [light petroleum-ethyl acetate (3 : 2)] gave the title compound 14b (0.89 g, 43% over two steps from 5) as a yellow oil (Found: C, 70.4; H, 5.8. C1,H,,OS requires C, 70.55; H, 5.92%); R,0.47 [light petroleum-ethyl acetate (3 :2)]; vmax(film)/cm-' 1658 (M)and 1546; 6,(400 MHz) 2.60 (1 H, dd, J3ax,3eq-16.2, J2ax,3ax 11.3, 3-HaJ, 2-78 (1 H, dd, J3ax,3eq -16-27J2ax,3eq 3-49 3- Heq),2.99 (2 H, d, Jvic 7.6, CHZPh), 3.65-3.75 (1 H, ddt, J2ax,3ax 11.3,J2ax,3eq3.4, Jvic7.6, 2-H), 6.18 (1 H, d, J5,6 10.1, 5-H) and 7.167.41 (6 H, m, 6-H + Ph); 6,(100 MHz) 39.95 (CH,Ph), 43.53 (C-3), 44.04 (C-2), 123.44 (C-5), 127.06 (C-4'), 128.59 7.1, 4'-H,), 1.36-1.71 (5 H, m, 1'-H, 2'- and 3'-H,), 2.18-2.26 (1 H,m, 1'-H), 3.06(1 H, dd, J2ax,3ax10.7,J3ax,3eq -17.1 3-Ha,), 3.14 (1 H, ddd, J2ax,3eq 4-07 J3ax,3eq -17.12 J3eq.5 1.2, 3-Heq), 3.60-3.53 (1 H, m, 2-H), 6.43 (1 H, dd, J3eq,51.2, J5.6 11.0, 5-H) and 7.25 (1 H, d, J5,6 11.0, 6-H); 6,(100 MHz) 13.66 (C-47, 22.30 (C-3'), 26.12 (C-2'), 28.04 (C-l'), 41.11 (C-3), 59.51 (C-2), 132.78 (C-5), 142.89 (C-6) and 192.00 (C-4); m/z 203 (l%, M+ + 1).2-Benzyl-2,3-dihydro-4H-thiin-4-one1,l-dioxide 15b. 2-Benzyl-2,3-dihydro-4H-thiin-4-one14b (0.91 g, 3.75 mmol) was treated with methanol (25 cm3), OXONE@ (3.51 g, 3.69 mmol) and water (25 cm3) for 30 h as described above. Centrifugal chromatography [light petroleum-ethyl acetate (4 : 1 to 3 :2)] followed by recrystallisation from CH2C1,-light petroleum gave the title compound 15b (0.91 g, 87%) as a solid, m.p.108-109.5 "C (Found: C, 60.7; H, 5.1; S, 13.7. C,,H,,O,S requires C, 60.99; H, 5.12; S, 13.59%); vm,x(Nujol)/cm-l 1693 (C=O),1336 (SO,, asym) and 1140 (SO,, sym); 6,(400 MHz) 2.79 (1 H, dd, J,,, -13.6, Jvic 11.3, CHHPh), 2.91 (1 H, ddd, J. CHEM. SOC. PERKIN TRANS. 1 1993 J3ax,3eq -17.4, J2ax,3eq 4-33 J3eq,5 1-29 3-Heq), 2.97 (1 H, dd, J2ax,3ax 10.2, J3ax,3eq -17-43 3-Hax), 3-59 (1 H, dd, Jgem -13-67 Joic 3.7, CHHPh), 3.70 (1 H, dddd, J2ax,3ax 10.2, J2ax,3eq 4.3, Juic 3.7,2-H), 6.39 (1 H, dd, J5,611.0, J3eq,511.3, Juic 1.2, 5-H) and 7.18-7.37 (6 H, m, 6-H + Ph); 6,(100 MHz) 31.83 (CH,Ph), 39.92 (C-3), 60.73 (C-2), 127.72 (C-4'), 129.18 (C-3', -5'), 129.32 (C-2', -6'), 133.17 (C-5), 134.32 (C-1'), 142.48 (C-6) and 191.58 (C-4); m/z 236 (2%, M').(c) General Procedure for the Preparation of P-Halogeno 2323 treated with trimethylsilyl iodide (1.37 g, 6.85 mmol) for 2 h and 2,2-dimethylpropane-1,3-diol(l.78g, 17.1 mmol) for 4 h as described above. Preparative centrifugal chromatography of the crude product with CH,C1, as eluent gave, after recrystal- lisation from ethanol, the title compound 2c (X = I) (1.04 g, 85%) as off-white needles, m.p. 152.5-153.5 "C (Found: C, 33.3; H, 4.8; S, 8.9. CloHl,IO,S requires C, 33.5; H, 4.8; S, 8.8%); R, 0.55 (CH,Cl,); vmax(CHC13)/cm-' 1397, 1367 (gem-dimethyl), 1334 (SO2, asym), 1135 (SO,, sym), 1115 and 1103 (ketal); 6,(400 MHz) 0.98 and 0.99 (2 x 3 H, 2 x s, 3-Me), 2.19 (1 H, Keta1s.-A solution of an unsaturated sulfone in acetonitrile at room temp. under nitrogen was treated with the appropriate '''7JlOax,llax 13-69 JlOeq.llax4.3, Jllax,lleq -14-6,11-Hax),2.52(I H, dd, J7ax,7eq -14.0, J7ax,8ax 13.4, 7-Ha,), 2.63 (1 H, dddd, trimethylsilyl halide.The resulting mixture was stirred for 1-24 h prior to the addition of the appropriate alcohol (or diol). After being stirred for a further 1-28 h, the reaction mixture was diluted with CH,Cl,, washed successively with water, aq. sodium hydrogen carbonate solution, and brine, and dried (MgSO,), and then the solvent was removed. Where tri- methylsilyl iodide was used, an additional wash with aq. sodium thiosulfate (10%) was incorporated after the initial water wash. 7-Iodo-1,4-dioxa-8-thiaspiro[4.5]decane8.8-dioxide 2a (X = I).A solution of 2,3-dihydro-4H-thiin-4-one 1,l-dioxide 12o (3.84 g, 26.3 mmol) in acetonitrile (105 cm3) was treated with trimethylsilyl iodide (10.51 g, 52.5 mmol) for 2 h and ethane-1,2- diol (8.15 g, 13 1 .O mmol) for 4 h as described above. The title compound 2a (X = I) (7.32 g, 88%) precipitated from the reaction mixture as an off-white, microcrystalline solid (pure by 'H NMR spectroscopy). Recrystallisation of an analytical sample from CH,Cl,-hexane gave the title compound as fine, off-white needles, m.p. 191-192 "C (decomp.) (Found: C, 26.4; H, 3.6. C7HllI0,S requires C, 26.43; H, 3.49%); Rf 0.79 (CH,Cl,); vmax(Nujol)/cm-' 1327 (SO,, asym) and 1130 (SO,, SYm); dH(400 MHz) 2-09 (1 H, dddd, J6eq,lOeq 3-63J9ax,lOeq 3-63 J9eq,10eq 3-67JlOax,loeq -13-89 lO-Heq), 2.45 (1 H, ddd, J9ax,lOax '4.0, J9eq,loax 3.6, J10ax,10eq -13.8, IO-Hax), 2.53 (I H, ddd, J6ax,6eq J6eq,7ax 3*7,J6eq,10eq 3.6, 6-Heq), 2.77 (l H, dd, J6ax,6eq -13*6? J6ax,7ax 13.6, 6-Hax), 3.38 (l H, ddd, J9eq,9ax -14-29J9eq,lOax 3-69J9eq,lOeq 3-69 9-Heq), 3-48 (1 H, ddd, J9ax,geq -14.2,J9ax,10ax 3.6, 9-Ha,), 3.96-4.07 (4 H, m, 2-, 14.0, J9ax,10eq 3-H,) and 5.13 (1 H, dd, J6ax,7ax 13.6, J6eq,7ax 3.7, 7-Hax); dc(100 MHz) 32.30 (C-7), 33.10 (C-lo), 45.83 (C-6), 46.01 (C-9), 64.90 and 65.27 (C-2, -3) and 105.87 (C-5); m/z 191 (18%, M+-I).4,4-Dibutoxy-2-iodothiane1,l -dioxideZb(X = I).Asolutionof 2,3-dihydro-4H-thiin-4-one 1,l -dioxide 1(4.75 g, 32.5 mmol) in acetonitrile (1 50 cm3) was treated with trimethylsilyl iodide (13.00 g, 65.0 mmol) for 2 h and butan-1-01 (24.1 g, 325 mmol) for 4 h as described above.Column chromatography of the crude product with CH,Cl, as eluent gave, after recrystallis- ation from diethyl ether-pentane, the title compound 2b (X = I) (1 1.01 g, 84%) as pale yellow needles, m.p. 39.5-41 .O "C (Found: C, 39.0; H, 6.4; S, 7.7. C13H,,I0,S requires C, 38.6; H, 6.2; S, 7.9%); R, 0.56 (CH,Cl,); ~,~,(CHCl~)/crn-~1334 (SO,, asymm), 1133 (SO,, sym) and 1104 (ketal); 6,(400 MHz) 0.92 and 0.95 (2 x 3 H, 2 x t, J6.9 and 6.9,4'-H,), 1.31-1.45 (4 H, J7eq,i leq 3-77 JlOeq,l leq 3-79 JlOax,lleq 3.7, J1 lax,1 leq -14.6,1 l-Heq), 3-05 (1 H, ddd, J7eq,7ax -14.0, J7eq,8ax 3-79J7eq,i leq 3-77 7-Heq), 3-30 (1 H, ddd, JlOax,loeq -14.0, JlOeq.1 lax 4-33JlOeq.1 leq 3-79 10-Heq1, 3-37 (1 H, ddd, J10ax,10eq -14.0, JlOax,l lax 13-69 JIOax,lleq 3.7, 10-Hax), 3.50 and 3.51 (2 x 2 H, 2 x s, 2- and 4-H2) and 5.04 (1 H, dd, J7ax,8ax 3.7, 8-Ha,); 13.4, J7eq,8ax 6,(22.4 MHz) 22.43 (C-Me,), 30.22 (C-3), 30.38 (C-11), 31.99 (C-8), 42.98 (C-7), 45.09 (C-lo), 70.38 and 70.75 (C-2 and -4) and 95.35 (C-6); m/z 233 (26%, M+ -I).8-Bromo-3,3-dimethyl-1,5-dioxa-9-thiaspiro[5.5]undecane9,-9-dioxide 2c (X = Br). A solution of 2,3-dihydro-4H-thiin-4-one 1,l-dioxide 1(1.OO g, 6.84 mmol) in acetonitrile (25 cm3) was treated with trimethylsilyl bromide (2.09 g, 13.7 mmol) for 2 h and 2,2-dimethylpropane-1,3-diol(3.56g, 34.2 mmol) for 4 h as described above.Preparative centrifugal chromatography of the crude product with CH,C1, as eluent gave, after recrystal- lisation from ethanol, the title compound 2c (X = Br) (1.20 g, 56%) as fine needles, m.p. 162-163 "C (Found: C, 38.6; H, 5.2; S, 10.25. CloHl,BrO,S requires C, 38.35; H, 5.47; S, 10.24%);R, 0.68 (CH,Cl,); vma,(CHC13)/cm-' 1398 and 1368 (gem-dimethyl), 1337 (SO,, asym), 11 18 (SO,, sym) and 1103 (ketal); 6,(400 MHz) 0.99 (6 H, s, 3-Me,), 2.20 (1 H, ddd, JIOax,llax 12.2, JlOeq,llax 5.2, Jllax,lleq -14.7, Il-HaX), 2.43 (I H, dd, J7ax,7eq -14.0,J7ax,8ax 12.8, 7-Hax), 2*60(1 H, dddd, J7eq,l leq 3-73 JlOax,lleq 3-77 JlOeq,lleq4*0, Jllax,lleq -14.7,11-Heq), 3-01 (1 H, ddd, J7ax,7eq -14*2,J7eq,8ax 4.0, J7eq,l leq 3*7, 7-Heq), 3*24 (1 H, ddd, JlOax,loeq -14-53JlOeq.1 lax 5-23JlOeq.1 leq 4-09 lO-Heq), 3.29 (1 H, ddd, JlOax,loeq -14.59J10ax.l lax 12.2,JlOax,l leq3.7, IO-Hax), 3.48-3.55 (4 H, m, 2-, 4-H,) and 4.84 (1 €3,dd, J7ax,8ax12.8, J7eq,8ax 4.0, %Ha,); 6,(100 MHz) 22.39 and 22.45 (3-Me), 30.20 (C-3), 30.46 (C-1 l), 40.92 (C-7), 46.31 (C-lo), 55.60 (C-8), 70.33 and 70.71 (C-2 and -4) and 95.29 (C-6); m/z 233 (75%, M+ -Br). 8-Chloro-3,3-dimethyl- 1,5-dioxa-9-thiaspiro[5 SJundecane 9,- 9-dioxide 2c (X = Cl).A solution of 2,3-dihydro-4H-thiin-4-one 1,l-dioxide 1 (1.00 g, 6.84 mmol) in acetonitrile (25 cm3) was treated with trimethylsilyl chloride (1.49 g, 13.7 mmol) for 2 h and 2,2-dimethylpropane-1,3-diol(3.56g, 34.2 mmol) for 4 h as described above.Preparative centrifugal chromatography of the crude product with CH,Cl, as eluent gave two compounds. The less polar fraction, after recrystallisation from ethanol, gave the title compound 2c (X = C1) (0.261 g, 14%) as fine off- white needles, m.p. 160.5-162 "C (Found: C, 44.8;H, 6.5; S, m, 3'-H,), 1.47-1.61 (4 H, m, 2'-H,), 2.22 (1 H, ddd, JSax,Seq12.05. CloH17C10,S requires C, 44.69; H, 6.38; S, 11.93%);R, -14*3,JSax,6ax l3.5, JSax,6eq 4*o, 5-Hax), 2.42 (1 H, dddd, J3eq,Seq 3-47J~ax~eq-14-39JSeq,6ax 3.7, JSeq,6eq 3-79 5-Heq), 2-54 (1 H, dd, J2ax,3ax 13-33J3ax,3eq -13.8, 3-Hax), 2-84 (1 H, ddd, Jzax,3eq 3.7, J3ax,3eq 3.4, 3-Heq), 3.26-3.31 (2 H, m, 6-Ha, and -13.8, J3eq,Seq 6-Heq), 3.38 and 3.40 (2 x 2 H, 2 x t, J6.9 and 6.9, 1'-H,) and 5-01 (1 H, dd, J2ax,3ax 13-39J2ax,3eq 3-73 2-Hax); dC(1OO MHz) 13.79and 13.86 (C-4'), 19.31 and 19.57 (C-3'), 30.88 (C-5), 31.75 and 31.80 (C-2'), 32.63 (C-2), 44.44 (C-3), 45.34 (C-6), 60.35 and 60.97 (C-1') and 97.74 (C-4); m/z 277 (3%, M+ -I).8-Iodo-3,3 -dimethyl- 1,5-dioxa-9-thiaspiro [5.5.]undecane 9,9- dioxide 2c (X = I). A solution of 2,3-dihydro-4H-thiin-4-one 1,l-dioxide 1 (0.50 g, 3.42 mmol) in acetonitrile (15 cm3) was 0.72 (CH,Cl,); vmax(CHC13)/cm-' 1398 and 1365 (gem-dimethyl), 1337 (SO,, asym), 11 16 (SO,, sym) and 1103 (ketal); 6,(400 MHz) 0.99 and 1.00 (2 x 3 H, 2 x s, 3-Me2), 2.20 (1 H,ddd, J1Oax.llax11.9, Jl0eq.llax5.2, Jllax,lleq -14.7, ll-Hax), 2.35 (1 H, dd, J7ax,7eq -14.0, J7ax,8ax 12.5, 7-Ha,), 2.58 (I H, dddd, J7eq,lleq 3-77 JlOax,lleq 3.7, JlOeq,lleq 4.0, Jllax,lleq-14.7, ll-Heq), 2.94 (1 H, ddd, J7eq,7ax -14.0, J7eq,8ax 4.0, J7eq,lleq 3-79 7-Heq)y 3-18 (1 H, ddd, JlOax,loeq -14-37JlOeq,llax 5.2, JlOeq.1 leq 4-09 lO-Heq), 3-22 (1 H, ddd, J10ax,10eq -14-39 JIOax,llax 3.7, 10-Hax), 3.45-3.56 (4 H, m, 2- and 11.9,JIOax,lleq 4-H,) and 4.79 (1 H, dd, J7ax,8ax 4.0, 8-Ha,); 6422.4 12.5, J7eq,8ax MHz) 22.43 (3-Me2), 30.46 (C-3), 30.56 (C-11), 40.13 (C-7), 46.56 (C-lo), 66.29 (C-8), 70.36 and 70.67 (C-2, -4) and 94.81 (C-6); m/z 269 (l%, M+ -1) and 233 (2, M+ -Cl).The more polar fraction, after recrystallisation from ethanol- light petroleum, gave 3,3-dimethyl- 1,5-dioxa-9-thiaspiro [5.5]-undec-7-ene (1.02 g, 64%) as off-white needles, m.p. 85-88 "C {Found: (CI) [M + NH4]+, 250.1113.CloH1604S requires [M -NH,], 250.1 113), R,0.41 (CH,Cl,); vma,(CHC13)/cm-' 1398 and 1367 (gem-dimethyl), 1308 (SO,, asym), 11 13 (SO,, sym) and 1099 (ketal); 6,(400 MHz) 0.91 and 1.07 (2 x 3 H, 2 x s, C-Me,), 2.50-2.56 (2 H, m, 11-H,), 3.33-3.53 (2 H, m, 10-H), 3.50 and 3.64 (4 H, ABq, JAB11.9, 2- and 4-H,), 6.36 (1 H, dt, J7,8 11.4, J7.11 1.5, 7-H) and 6.79 (1 H, dt, J7,811.4, J8,101.2, 8-H); 6,(22.5 MHz) 21.80 and 22.24 (3-Me2), 29.70 (C-3), 30.83 (C-11), 47.46 (C-lo), 70.39 (C-2, -4), 91.20 (C-6), 129.61 (C-7) and 132.95 (C-8); m/z 168 (9%, M+ -SO,). trans-6-Benzyl-9-iodo-1,4-dioxa-8-thiaspiro[4.S]decane83-dioxide 10a.A solution of unsaturated sulfone 9a (1-00g, 4.23 mmol) in acetonitrile (100 cm3) was treated with trimethylsilyl iodide (1.69 g, 8.45 mmol) for 1 h and ethylene glycol (1.3 1 g, 21.1 mmol) for 24 h as described above.The crude material was purified by preparative centrifugal chromatography with CH,Cl, as eluent to give the title compound 10a (1.61 g, 93%) as a solid, m.p. 195-199 "C (decomp.) (Found: C, 41.2; H, 4.1. C1,Hl7IO4S requires C, 41.19; H, 4.20%); R, 0.39 (CH,Cl,); vma,(CHC13)/cmp1 1322 (SO,, asym) and 1124 (SO,, sym); 6,(400 MHz) 2.27 (1 H, dd, Jsem -13.3, Juic 11.5, CHHPh), 2-59 (1 H, dd, Jgax, 1Oeq 4-49J1 Oax, 1Oeq -13-99 1 O-Heq), 2-66 (1 H, dd, J9ax,10ax12.8. J1Oax,lOeq-13.9, 10-Hax), 2.68-2.74 (1 H, m, 6-Ha,), 3.15 (1 H, dd, Jgem-13.3, JviClc3.7, CHHPh), 3.16-3.18 (2 H, m, 7-H,), 4.09-4.15 (4 H, m, 2- and 3-H), 5.08 (1 H, dd, J9ax,10ax12.8, J9ar,10eq4.4 9-Ha,), 7.09-7.13 (2 H, m, 2'-, 6'-H) and 7.25-7.35 (3 H, m, 3'-, 4'-, 5'-H); 6,(100 MHz) 32.40 (C-9, 33.20 (CH,Ph), 45.20 (C-6), 45.34 (C-lo), 49.70 (C-7), 65.72 and 65.86 (C-2, -3), 107.71 (C-5), 126.91 (C-4'), 128.90 (C-3', -57, 129.12 (C-2', -6') and 137.17 (C-1'); m/z 279 (25%).trans-6-Allyl-9-iodo-1,4-dioxa-8-thiaspiro[4.5]decane8,8-di-oxide lob.A solution of 3-allyl-2,3-dihydro-4H-thiin-4-one1,l-dioxide 9b (0.084, g, 0.45 mmol) in acetonitrile (1.5 cm3) was treated with trimethylsilyl iodide (0.198 g, 0.99 mmol) for 100 min and ethylene glycol (0.140 g, 2.25 mmol) for 28 h as described above. Column chromatography (CH,Cl, as eluent) gave the title compound 10b as a solid (0.154 g, 96%), m.p.140.5- 144 "C; R, 0.54 (CH,Cl,) (Found: C, 33.9; H, 4.2. CloHl,IO,S requires C, 33.53; H, 4.22%); {Found: (CI) [M + NH4]+, 376.0079. CloHl,IO,S requires [M + NH,], 376.0080); vma,-(CDCl,)/cm-' 1320 (SO,, asym) and 1135 (SO,, sym); 6,(60 MHz) 1.52-3.68 (7 H, m, 1'-, 7- and 10-H, and 6-H), 4.07 (4 H, br s, 2- and 3-H,), 4.80-5.31 (3 H, m, 9-H and 3'-H,) and 5.35- 6.08 (1 H, m, 2'-H); 6,(22.5 MHz) 31.7 (C-l'), 32.5 (C-9), 42.8 (C-6), 45.5 (C-lo), 50.0 (C-7), 65.8 and 65.6 (C-2, -3), 107.7 (C-5), 118.6 (C-3') and 134.3 (C-2'); m/z 23 1 (M' -I, 22%). 7-Bu ty l-9-iodo-1,4-dioxa-8-th iaspiro [4. 5ldecane 8,%dioxide 16a. A solution of 2-butyl-2,3-dihydro-4H-thiin-4-one1,l-dioxide 15a (0.64 g, 3.16 mmol) in acetonitrile (12 cm3) was treated with trimethylsilyl iodide (1.46 g, 7.31 mmol) for 1 h and ethane-1,3-diol(l.l7g, 18.83 mmo1)for 18 hasdescribedabove.Preparative centrifugal chromatography [light petroleum-ethyl acetate (7 : 3)] gave the title compound 16a (1.07 g, 90%) as a solid, chromatographically identical mixture of diastereoiso- mers (3:1), m.p. 81-83 "C (Found: C, 35.55; H, 5.1; S, 8.5. Cl1H1,IO,S requires C, 35.30; H, 5.12; S, 8.57%);R,0.27 [light petroleum*thyl acetate (7 : 3)]; vmax(Nujol)/cm-l 1309 (SO,, asym) and 1 11 5 (SO,, sym); m/z247 (M+ -I, 15%). Successive recrystallisation of the mixture of isomers from ethyl acetate- light petroleum afforded a sample of the major cis-isomer ( > 99 :1, cis :trans). cis-Isomer: 6,(400 MHz) 0.92 (3 H, t, J3,,,,7.2,4'-H,), 1.21-1.44 (4 H, m, 2'- and 3'-H,), 1.441.55 (2 H, m, 1'-H), 2.07 (1 H, J.CHEM. SOC. PERKIN TRANS. 1 1993 ddd, J10eq,6eq 4*o,J7ax,6eq 4-o, J6ax,6eq -l4.0, 6-Heq), 2m15 (l H, dd, J7ar,6ax l4.0, J6ax,6eq -l4-0, 6-Hax), 2-51 (1 H, ddd, J10ax,10eq -13.8, JlOeq,9ax 3-79 JlOeq,6eq 4.0, lo-Heq), 2-73 (1 H, dd, J10ax,10eq -13-87 JlOax,9ax 13-83 lo-Hax), 3.23-3-33 (1 H, m, 7-Ha,), 3.99-4.02 (4 H, m, 2- and 3-H2) and 5.01 (1 H, dd, J1 Oax,9ax 13.8, JlOeq,9ax 4-09 9-Hax); 6,(100 MHz) 13-90 (C-4'1, 22.02 (C-3'),26.08 (C-2'),28.05 (C-1'), 32.42 (C-9), 38.57 (C-6), 45.63 (C-lo), 56.25 (C-7), 64.90 and 64.67 (C-2 and -3) and 105.96 (C-5). trans-Isomer:6,(400 MHz) 0.94 (3 H, t, J3,,,,7.2,4'-H,), 1.21- 1.44(4 H, m, 2'- and 3'-H,), 1.82-1.94 (2 H, m, 1'-H2), 2.09-2.16 (l H,m, 6-Heq),2-36(1 H,dd,J7eq,6a~~*~, J6ax,6eq -14*7, lo-Hax), 2*54 H, ddd, J1Oax,lOeq -l0.8, JlOeq.9ax 4-29 JlOeq,6eq 2*4, lo- Heq), 2.62(1 H, dd, J10ax,10eq -10.8,JlOax,9ax 10-8,10-Hax), 3.32- 3.39 (1 H, m, 7-He,), 3.99-4.02 (4H, m, 2- and 3-H,) and 5.1 1 (1 H, dd, J10ax,9ax4.2, 9-Hax); dc(100 MHz) 13.90 (C-4'), 21.91 (C- 3'),26.97 (C-2'), 28.75 (C-1'), 29.47 (C-9), 35.33 (C-6), 44.61 (C- lo), 55.82 (C-7), 64.20 and 64.84 (C-2, -3) and 105.68 (C-5).cis-7-Benzyl-9-iodo-1,4-dioxa-8-thiaspiro[4.S]decane 8,8-dioxide 16b.A solution of 2-benzyl-2,3-dihydro-4H-thiin-4-one 1,l-dioxide 15b (0.76 g, 3.2 mmol) in acetonitrile (20 cm3) was treated with trimethylsilyl iodide (1.35 g, 6.76 mmol) for 1 h and ethane- 1,2-diol(l .OO g, 16.14 mmol) for 24 h as described above.Preparative centrifugal chromatography [light petroleum-ethyl acetate (3 :2)] gave the title compound 16b (1.10 g, 84%) as a crystalline solid, m.p. 128-1 30 "C (Found: C, 41.4; H, 4.1; S, 7.95. C14H17104S requires C, 41.19; H, 4.19; S. 7.85%);R,0.76 [light petroleum-ethyl acetate (3 :2)]; vma,(Nujol)/cmpl 131 8 (SO,, asym) and 1116 (SO,, sym); 6,(400 MHz) 1.83 (1 H, ddd, J10eq,6eq 3.7, J7ax,6eq 3-77 J6ax,6eq -14*0, 6-Heq), 2*12 (1 H, dd, J7ax,6ax 13-79 J6ax6eq -14.0 6-H,,), 2-50 (1 H, ddd, J10ax,Ioeq -13.4,J10eq,9ax 3.7, J10eq,6eq 3.7 10-Heq)7 2*75 (1 H, dd, JlOax,lOeq -13.4,J10ax,9ax13.4, 10-Ha,),2.77(1 H,dd,Jgem -14.0,Juic12.0, CHHPh), 3.55-3.61 (2 H, m, 7-H and CHHPh), 3.76-3.95 (4 H, m, 2- and 3-H2), 5-10 (1 H, dd, JlOax,9ax 13-49JlOax,9eq 3-77 9-Hax) and 7.17-7.35 (5 H, m, Ph); 6,(100 MHz) 32.16 (C-9), 32.31 (CH,Ph), 37.92 (C-6), 46.00 (C-lo), 57.39 (C-7), 64.76 and 65.04 (C-2, -3), 106.15 (C-5), 127.19 (C-47, 128.90 (C-3', -57, 129.27 (C-2', -6') and 135.72 (C-1'); m/z 204 (M+ -I -Ph, 100%).Careful analysis of the product by 'H NMR spectroscopy indicated the presence of a small amount of the trans-isomer (cis: trans -96 :4). (d) General Procedure for Preparation of Episulfones.-A solution of the P-halogeno ketal in dry THF at -78 "C under nitrogen was treated with a solution of freshly sublimed potassium tert-butoxide in dry THF. The solution was stirred, then quenched at -78 "C with saturated aq.ammonium chloride. The mixture was then diluted with water and subjected to a standard CH,Cl, work-up. 7,8-Epithio-1,4-dioxaspiro[4.4]nonane S,S-dioxide 3a. A solution of 7-iodo- 1,4-dioxa-8-thiaspir0[4.Sldecane 8,8-dioxide 2a (0.50 g, 1.57 mmol) in a mixture of dry DMSO (20 cm3) and dry THF (30 an3)at 0 "C under nitrogen was treated with a THF solution of freshly sublimed potassium tert-butoxide (1 .O mol dmp3; 2.00 cm3, 2.00 mmol). After being stirred for 3 h, the reaction mixture was worked up as described above to give, after preparative centrifugal chromatography [CH,Cl,-ethyl acetate (9 :l)], the title episulfone 3a (0.26 g, 87%) as a cream- coloured solid, m.p. 148-150 "C (decomp.) (Found: C, 43.9; H, 5.3. C7Hlo0,S requires C, 44.2; H, 5.3%); R, 0.08 [CH,C12-ethyl acetate (9 :l)]; vma,(Nujol)/cm-' 131 1 (SO,, asym) and 1105 (SO,, sym); 6,(400 MHz) 2.35-2.43 (2 H, m, 6- and 9-Ha,), 2.W2.48 (2 H, m, 6- and 9-He,), 3.69-3.73 (2 H, m, 7- and 8-H) and 3.85-3.98 (4 H, s, 2- and 3-H,); 6,(100 MHz) 35.82, (C-6, -9), 46.27 (C-7, 4,64.17 and 65.88 (C-2, -3) and 122.11 (C-5);m/z191 (l%,Mf f l)and126(100,Mf -SO,).3,3-Dibutoxy-6-thiabicycl0[3.1.O]hexane 6,6-dioxide 3b. A J. CHEM. SOC. PERKIN TRANS. 1 1993 solution of 4,4-dibutoxy-2-iodothiane1,l-dioxide 2b (0.50 g, 1.23 mmol) in dry THF (25 cm3) was treated with potassium tert-butoxide (0.30 g, 2.67 mmol) for 10 min as described above to give, after preparative centrifugal chromatography [CH,Cl,- light petroleum (1 :l)], the title episulfone 3b (0.28 g, 82%) as a pale yellow viscous oil {Found: (CI) [M + l]', 277.1470.C,,H,,O,S requires [M + 11, 277.1474); R, 0.46 [CH,Cl,- light petroleum (1 :l)]; vma,(CHC13)/cm-' 1323 (SO,, asym), 1134 (SO,, sym) and 1104 (ketal); 6,(400 MHz) 0.92 and 0.93 (2 x 3 H, 2 x t, J6.9 and 6.9,4'-H,), 1.31-1.42 (4 H, m, 3'-H,), 1.48-1.57 (4 H, m, 2'-H,), 2.18-2.27 (2 H, m, 2-, 4-H), 2.52-2.58 (2 H, m, 2-, 4-H), 3.36 (2 H, t, J 6.7, 1'-H,), 3.44 (2 H, t, J6.7, 1'-H,) and 3.57-3.62 (2 H, m, 1-, 5-H); dc(lOO MHz) 13.78 (C-4'), 19.30 and 19.41 (C-3'), 31.76 and 31.83 (C-2'), 33.07 (C-2, -4), 46.70 (C-1, -9,60.87 and 63.93 (C-1') and 115.50 (C-3); m/z 275 (17%, M+ -1) and (3, M+ -SO,). 2,3-Epithio-8,8-dimethyl-6,1O-dioxaspiro[4.5]decaneS,S-di-oxide 3c.1. From 8-iodo-3,3-dimethyl- 1,5-dioxa-9-thiaspiro- [5.5]undecane 9,g-dioxide 2c (X = I). A solution of 8-iodo-3,3-dimethyl-1,5-dioxa-9-thiaspir0[5.5]undecane 9,g-dioxide 2c (X = I) (0.129 g, 0.47 mmol) in dry THF (10 cm3) was treated with potassium tert-butoxide (0.079 g, 0.70 mmol) for 10 min as described above to give, after preparative centrifugal chromato- graphy [CH,Cl,-light petroleum (4 :l)], the title episulfone 3c (0.092 g, 85%) as a solid, m.p. 94.0-95.0 "C (Found: C, 5 1.8; H, 6.95; S, 13.76. C,,H,,O,S requires C, 51.71; H, 6.94; S, 13.80%) {Found: (CI) [M + NH4]+, 250.1113. CloH1604S requires [M + NH,], 250.1113); R, 0.44 (CH,Cl,); ~,,,(CHCl~)/crn-~ 1397 and 1365 (gem-dimethyl), 1325 (SO,, asym), 1138 (SO,, sym) and 1 11 5 (ketal); dH(400 MHz) 0.98 (6 H, s, 8-Me,), 2.26 (2 H, m, 1-, 4-Ha3, 2.76 (2 H, m, I-, 4-H,,), 3.45 (2 H, s, 7-H,), 3.49 (2 H, s, 9-H,) and 3.61 (2 H, m, 2-, 3-H); dc(lOO MHz) 22.25 (%Me,), 29.95 (C-8), 32.95 (C-1, -4), 46.58 (C-2, -3), 71.38 and 73.61 (C-7, -9) and 113.56 (C-5); m/z 168 (50%, M' -SO,).2. From 8-bromo- 3,3 -dimethyl- 1,5-dioxa-9- thiaspir o[5.5] -undecane 9,9-dioxide 2c (X = Br). A solution of 8-bromo-3,3- dimethyl-1,5-dioxa-9-thiaspiro[5.5]undecane 9,g-dioxide 2c (X = Br) (0.200 g, 0.64 mmol) in dry THF (1 5 cm3) was treated with potassium tert-butoxide (0.1 10 g, 0.98 mmol) for 15 min as described above to give, after preparative centrifugal chromato- graphy [CH,Cl,-light petroleum (4: l)], the title episulfone 3c (0.1 10 g, 74%) as a solid, with data identical with those above.3. From 8-chloro-3,3-dimethyI-1,5-dioxa-9-thiaspiro[5.5]un-decane 9,g-dioxide 2c (X = Cl). A solution of 8-chloro-3,3- dimethyl-1,5-dioxa-9-thiaspir0[5.5]undecane 9,g-dioxide 2c (X = C1) (0.129 g, 0.47 mmol) in THF (1 0 cm3) was treated with potassium tert-butoxide (0.079 g, 0.70 mmol) for 10 min as described above to give, after preparative centrifugal chromato- graphy [CH,Cl,-light petroleum (4 :l)], the title episulfone 3c (0.092 g, 85%) as a solid, with data identical with those above. r-6-Benzyl-t-7,t-8-epithio-l,4-dioxaspiro[4.4]nonaneS,S-di-oxide lla. A solution of iodo ketal10a (0.130 g, 0.32 mmol) in THF (20 cm3) was treated with potassium tert-butoxide (0.080 g, 0.71 mmol) in THF (5 cm3)for 3 min as described above.Preparative centrifugal chromatography with CH,Cl, as eluent gave the title compound lla (0.076 g, 90%) as a solid, m.p. 106- 108 "C (decomp.) (Found: C, 60.1; H, 5.7. C14H1604S requires C, 59.98; H, 5.75%) {Found: (CI) [M + NH,]', 298.1120. Cl,H160,S requires [M + NH,], 298.1 113); R, 0.55 (CH,Cl,); v,,,(CHCl,)/cm-' 1310 (SO,, asym) and 1135 (SO,, sym); 6,(400 MHz) 2.3S2.40 (2 H, m, CH2Ph), 2.74 (1 H, dd, J9a,98 -14.3, J8,ga 11.2, %Ha), 2.95 (1 H, dd, Jga,gB 4.8, g-H,), 3.05 (1 H, ddd, J7.8 5.8, J8,sa 11.2, J8.98 4.8,8-H), 3.36 (1 H, dd, J6.7 10.3, J7,8 5.8, 7-H), 3.56 (1 H, ddd, Joic6.6, Jvic7.7, J6.7 10.3, 6-H), 3.844.08 (4 H, m, 2-, 3-H,) and 7.18-7.33 (5 H, m, Ph); dC(100 MHz) 32.07 (C-9), 34.44 (CHZPh), 44.85 (C-6), 46.64 (C-8), 50.17 (C-7), 64.82 and 66.08 (C-2, -3), 121.33 (C-5), 126.62 (C-4'), 128.44(C-2', -6'), 128.77 (C-3', -5') and 134.41 (C-1'); m/z 216(27%, M' -SO,).r-6-Allyl-t-7,t-8-epithio-1,4-dioxaspir0[4.4]nonane S,S-diox-ide llb. A solution of the iodo ketal10b (0.107 g, 0.30 mmol) in THF (5 cm3) was treated with potassium tert-butoxide (0.040 g, 0.36 mmol) in THF (2 cm3) for 2.5 h at -78 "C as described above and was then allowed to warm to room temp. over a period of 1.5 h. The reaction mixture was then quenched by the addition of water (5 cm3) and worked up as described above. The residue was purified by column chromatography [diethyl ether-light petroleum (2 :3)] to give 6-allyl-1,4-dioxaspiro- 14.41non-7-ene 12b (0.010 g, 20%) (see later) followed by the title compound llb (0.045 g, 65%) as a solid, m.p.64-68 "C {Found: (CI) [M + NH4]+, 248.0962. C,oHl,O,S requires [M + NH,], 248.0956); R, 0.48 [diethyl ether-light petroleum (7 :3)] J; v,,(Nujol)/cm-' 1305 (SO,, asym) and 1140 (SO,, sym); 6,(60 MHz) 2.04-2.84 (5 H, m, 1'- and 9-H,, and 6-H), 3.14- 3.80 (2 H, m, 7-, 8-H), 3.96 (4 H, br s, 2-, 3-H), 4.84-5.38 (2 H, m, 3'-H,) and 5.46-6.16 (1 H, m, 2'-H); m/z (CI) 248 (12%, M + NH4]+ and 167 (100, [M + 1 -SO,])'. (e) Preparation of Cyclopentenes.-1,4- Dioxaspiro[4.4)non-7- ene 4a. A solution of potassium tert-butoxide in THF (1 .O mol dmP3; 3.30 cm3, 3.30 mmol) was added to a stirred suspension of 7-iodo-1,4-dioxa-8-thiaspiro[4.5]decane8,8-dioxide 2a (0.42 g, 1.32 mmol) in dry diethyl ether (50 cm3) at -78 "C under nitrogen.The reaction mixture was allowed to warm to room temp. during 6 h. Saturated aq. ammonium chloride (60 cm3) was added and a standard ethereal work-up was carried out. 'H NMR spectroscopy of the resulting oil (0.134 g) indicated the presence of Bu'OH and the highly volatile 1,6dioxaspiro- [4.4]non-7-ene 4a22 (Found: [M + HI', 127.0759. Calc. for C7H1002: [M + HI, 127.0759); R, 0.30 (CH,Cl,); vmaX-(film)/cm-' 2884 (CH str), 1327 and 1019; 6,(90 MHz) 2.65 (4 H, br s, 6-, 9-H,), 3.91 (4 H, br s, 2-, 3-H,) and 5.62 (2 H, br s, 7-, 8-H); dc(22.5 MHz) 43.14 (C-6, -9), 64.21 ((2-2, -3), 117.45 (C-5) and 128.07 (C-7, -8).4,4-Dibutoxycyclopentene4b. 1. From 4,4-dibutoxy-2-iodo- thiizne 1,l -dioxide 2b. A solution of 4,4-dibutoxy-2-iodothiane, 1,l-dioxide 2b (0.80 g, 1.98 mmol) in dry THF (25 cm3) at room temp. under nitrogen was treated with a solution of potassium tert-butoxide (0.67 g, 5.97 mmol) in dry THF (5 cm3). After being stirred for 2 h at room temp., the reaction mixture was quenched with saturated aq. ammonium chloride (25 cm3), then was subjected to a standard CH2Cl, work-up. The crude product was purified by distillation (Kugelrohr) to give the title alkene 4b (0.39 g, 93%) as a mobile liquid, b.p. 80 "C/0.5 mmHg (Found: C, 73.7; H, 11.7. C13H2402 requires C, 73.54; H, 11.39%); Rf0.92 (CH,Cl,); v,,,(film)/cm-' 1622 (M)and 1105 (ketal); 6,(400 MHz) 0.92 (6 H, t, J 7.0, 4'-H,), 1.24-1.58 (8 H, m, 2'-, 3'-H,), 2.54 (4 H, br s, 3-, 5-H,), 3.43 (4 H, t, J 6.7, 1'-H2) and 5.65 (2 H, br s, 1-, 2-H); 6,(100 MHz) 13.89 (C-4'), 19.50 (C-3'), 32.14 (C-2'), 41.92 (C-3, -9,61.38 (C-1'), 111.16 (C-4) and 127.80 (C-1, -2); m/z 212 (lo%, M+).2. From 3,3-dibutoxy-6-thiabicycloC3.1.O] hexane 6,6-dioxide 3b. A solution of 3,3-dibutoxy-6-thiabicyclo[3.1.O]hexane 6,6- dioxide 3b (0.124 g, 0.45 mmol) in dry THF (10 cm3) at room temp. under nitrogen was treated with a solution of potassium tert-butoxide (0.10 g, 0.91 mmol) in dry THF (5 cm3) for 2 h. Work-up and purification as described above gave the title alkene 4b (0.086 g, 91%) with data identical with those above. 8,8-Dimethyl-6,1O-dioxaspiro[4.5]dec-2-ene4c.1. From 8-iodo- 3,3 -dimethyl- 1 ,5-dioxa-9-thiaspiro[5.51 undecane 9,g-diox- ide 2c. Freshly sublimed potassium tert-butoxide (0.62 g, 5.56 mmol) was added to a solution of 8-iodo-3,3-dimethyl-l,5-dioxa-9-thiaspiro[5.5]undecane 9,9-dioxide 2c (1.OO g, 2.78 mmol) in dry THF (50 cm3) under nitrogen at room temp. The solution was stirred for 1 h, then was quenched with saturated aq. ammonium chloride (50 cm3). A standard CH,Cl, work-up, followed by Kugelrohr distillation of the crude material, gave the title alkene 4c23(0.425 g, 91%) as a liquid, b.p. 35 OC/O.5 mmHg (Found: C, 71.2; H, 9.4. Calc. for C1,H,,02: C, 71.39; H, 9.59%); R, 0.90 (CH,Cl,); v,,(film)/cm-' 1622 (GC), 1395, 1363 (gem-dimethyl), 1120 and 1106 (ketal); dH(4O0 MHz) 0.99 (6 H, S, 8-Me,), 2.66 (4 H, S, 1-, 4-H2), 3.52 (4 H, S, 7-, 9-H,) and 5.67 (2 H, s, 2-, 3-H); 6,(100 MHz) 22.37 (8-Me2), 29.97 (C-8), 49.32 (C-1, -4), 71.85 (C-7, -9), 109.16 (C-5) and 127.69 (C-2, -3); m/z 168 (44%,M').2. From 2,3-epithio-8,8-dimethyl-6,1O-dioxaspiro[4.5]decane S,S-dioxide 3c. A solution of 2,3-epithio-8,8-dimethyl-6,10-dioxaspiro[4S]decane S,S-dioxide 3c (0.232 g, 1 .OO mmol) in dry THF (15 cm3) under nitrogen at room temp. was treated with a solution of potassium tert-butoxide (0.224 g, 2.00 mmol) in dry THF (5 cm3) for 1 h. Work-up and purification as described above gave the title alkene 4c (0.156 g, 93%) with data identical with those above. 6-Benzyl-l,4-dioxaspiro[4.4]non-7-ene12a. 1.From trans-6- benzyl-9-iodo-1,4-dioxa-8-thiaspir0[4.5]decane8.8-dioxide 10a. A solution of potassium tert-butoxide (0.050 g, 0.45 mmol) in dry THF (5 cm3) was added dropwise under nitrogen to a stirred solution of compound 10a (0.122 g, 0.30 mmol) in dry THF (5 cm3) in a solid CO,-carbon tetrachloride-bath. The mixture was allowed to attain room temp. and was stirred for a further 20 h, when TLC (CH,Cl,) indicated the continued presence of episulfone lla.A further portion of potassium tert- butoxide (0.034 g, 0.30 mmol) was added and the mixture was stirred for a further 2.5 h, when brine (10 cm3) was added. A standard CH2Cl, work-up, followed by column chromato- graphy (CH,Cl,), gave 6-benzyl- 1,4-dioxaspiro[4.4]non-7-ene 12a (0.055 g,85%) as an oil, R, 0.72 (CH,Cl,); v,,,/cm-' 1495 and 700; 6,(400 MHz) 2.49-2.63 (3 H, m, 9-H, and CHHPh), 2.89 (1 H, dd, J,,, -13.6, JUi,5.9, CHHPh), 2.96-3.01 (1 H, m, 6-H), 3.77-3.96 (4 H, m, 2-, 3-H,), 5.59-5.63 (1 H, m, 7-H), 5.70- 5.74 (1 H, m, 8-H) and 7.15-7.29 (5 H, m, Ph); 6,(100 MHz) 35.67 (CH,Ph), 43.02 (C-9), 53.54 (C-6), 64.03 and 64.71 (C-2, -3), 117.53 (C-5), 125.68 (C-4), 127.44 (C-7), 128.13 (C-2', -6'), 128.99 (C-3', -5'), 132.91 (C-8) and 140.81 (C-1'); m/z 216 (29%, M +).2. From r-6- benzyl- t-7, t-8-epithio- 1,4-dioxaspir0[4.4)nonane S,S-dioxide lla and base. A solution of episulfone lla (0.034 g, 0.12 mmol) in dry THF (2 cm3), stirred under nitrogen in a solid CO,-carbon tetrachloride-bath, was treated dropwise with a solution of potassium tert-butoxide (0.017 g, 0.15 mmol) in dry THF (1 cm3).The mixture was stirred at the same temperature for 30 min, then at room temp. for 2 h, when a further portion of potassium tert-butoxide (0.017 g, 0.15 mmol) was added. The mixture was stirred for 30 min and then was quenched with brine (2 cm3). Work-up and purification as described above gave the title alkene 12a (0.156 g, 93%) with data identical with those above. 3. By thermolysis of r-6-benzyl-t-7,t-8-epithio-1,4-dioxaspiro-[4.4]nonane S,S-dioxide lla. Episulfone lla (0.065 g, 0.23 mmol) was heated, under nitrogen in a Kugelrohr oven, rapidly to 90 "C then to 110 "C during 20 min, when no solid material remained. The residue was subjected to column chromato- graphy as described above to give the title alkene 12a (0.044 g, 88%) with data identical with those above.6-AIIyl-I,4-dioxaspiro[4.4]non-7-ene12b. A solution of potassium tert-butoxide (0.140 g, 1.25 mmol) in dry THF (7 cm3) was added dropwise under nitrogen to a solution of the iodo ketal 10b (0.179 g, 0.50 mmol) in dry THF (7 cm3) at -78 "C. The mixture was allowed to attain room temp. and was stirred for 16 h. A further portion of potassium tert-butoxide (0.056 g, 0.50 mmol) was added and the mixture was stirred at room temp. for a further 1 h. The reaction mixture was diluted with brine (5 cm3) and water (5 cm3), and a standard CH2Cl, J. CHEM. SOC. PERKIN TRANS. I 1993 work-up followed by column chromatography (CH,Cl,) gave 6- allyl-l,4-dioxaspiro[4.5]non-7-ene12b '(0.072 g, 87%) as an oil, R, 0.86 [diethyl ether-light petroleum (1 :l)]; v,,,/cm-' 2880, 1640 (W),1140 and 1030; 6,(60 MHz) 1.81-2.90 (5 H, m, 1 '-and 9-H, and 6-H), 3.91 (4 H, s, C-2,3-H), 4.77-5.2 1 (2 H, m, 3'-H,) and 5.31-6.23 (3 H, m, 7-, 8-and 2'-H); 6,(22.5 MHz) 33.9 (C-l'), 43.0 (C-9), 51.6 (C-6), 64.8 and 64.0 (C-2, -3), 115.5 (C-3'), 117.5 ((2-5) and 127.3, 132.9 and 137.1 (C-7, -8 and -2'); m/z 166 (4%, M').3-Butykyclopent-2-enone18a. A solution of potassium tert- butoxide in THF (1.0 mol dm-3; 2.05 cm3, 2.05 mmol) was added to a stirred solution of 7-butyl-9-iodo-l,4-dioxa-8-thiaspiro[4S)decane 8,8-dioxide 16a ( -3:1 mixture of dia- stereoisomers) (0.506 g, 1.35 mmol) in dry THF (20 cm3) at -78 "C under nitrogen.The reaction mixture was allowed to warm to 0 OC, then saturated aq. ammonium chloride (10 cm3) was added. The mixture was given a standard ethereal work-up followed by preparative centrifugal chromatography [hexane- ethyl acetate (7 :3)] to produce 3-butylcyclopent-2-enone 18a (0.16 g, 86%) as an oil with consistent spectral properties (which were also in accord with literature 28 data). 7-Benzyl-1,4-dioxaspiro[4.4]non-7-ene17b. A solution of potassium tert-butoxide in THF (1 .O mol dm-3; 2.35 cm3, 2.35 mmol) was added to a stirred solution of 7-benzyl-9-iodo- 1,4- dioxa-8-thiaspiro[4.5]decane-8,8-dioxide 16b (0.53 g, 1.29 mmol) in dry THF (35 cm3) at -78 "C under nitrogen. The reaction mixture was allowed to warm to room temp., then saturated aq.ammonium chloride (10 an3)was added. A standard CH,C12 work-up, followed by preparative centrifugal chromatography [light petroleum to light petroleum-ethyl acetate (7 :3)], gave 7-benzyl-l,4-dioxaspiro[4.4]non-7-ene17b (0.175 g, 62%) as an oil with consistent spectral properties (which were also in accord with literature data). The more polar fractions were found to contain 3-benzyl- cyclopent-2-enone 18b (0.065 g, 29%) as a pale yellow oil with consistent spectral properties (which were also in accord with literature 30 data). Acknowledgements We are grateful to the SERC for the award of studentships (S. M. J. and A. G. S.) and a postdoctoral research assistantship (S.M. P.). We would also like to thank the SERC WH-400 NMR spectroscopic service (Warwick) and Mass Spectrometry Centre (Swansea) for their assistance, Courtaulds Research for financial support and Drs. J. C. Marriott and P. G. Urben of Courtaulds for their interest. References 1 L. Ramberg and B. Backlund, Ark. Kemi. Mineral. Geol., 1940,27, Band 13A, 1 (Chem. Abstr., 1940,34,4725). 2 For reviews see: L. A. Paquette, Org. React., 1977, 25, 1 and references therein; U. Zoller, in Heterocyclic Compoundr, ed. A. Hassner, Wiley, Chichester, 1983, vol. 42, Part 1, ch. 3, pp. 499-535; F. S. Guziec and L. J. Sanfilippo, Tetrahedron, 1988,44,6241; S. Oae and Y. Uchida (ch. 12) and S.Braverman (ch. 13) in The Chemistry of Sulphones and Sulphoxides, eds.S. Patai, Z. Rappoport and C. J. M. Stirling, Wiley, Chichester, 1988; J. M. Clough, in Comprehensive Organic Synthesis, eds. B. M. Trost and I. Fleming, Pergamon Press, Oxford, 1991, vol. 3, ch. 3.8. 3 C. Y. Meyers, A. M. Malte and W. S. Matthews, J. Am. Chem. Soc., 1969, 91, 7510; see also E. Vedejs and S. P. Singer, J. Org. Chem., 1978,43,4884. 4 J. J. Burger, T. B. R. A. Chen, E. R. de Waard and H. 0.Huisman, Tetrahedron, 1981,37,417. 5 D. Scarpetti and P. L. Fuchs, J.Am. Chem. SOC.,1990,112,8084 and references therein. 6 J. B. Hendrickson, G. J. BoudreauxandP. S. Palumbo, J. Am. Chem. SOC.,1986,108,2358; J. B. Hendrickson and P. S. Palumbo, J. Org. Chem., 1985,50,2110. J. CHEM. SOC. PERKIN TRANS.1 1993 7 H. Matsuyama, Y. Miyazawa, Y. Takei and M. Kobayashi, J. Org. Chem., 1987,52, 1703 and references therein. 8 E. Block, M. Aslam, V. Eswarakrishman, K. Gebreyes, J. Hutchinson, R. Iyer, J. A. Laffitte and A. Wall, J. Am. Chem. SOC., 1986,108,4568. 9 H. Matsuyama, Y. Ebisawa, M. Kobayashi and N. Kamigata, Heterocycles, 1989, 29, 449; T. Fujisawa, B. I. Mobele and M. Shimizu, Tetrahedron Lett., 1991,32,7055. 10 G. Casy and R. J. K. Taylor, Tetrahedron, 1989,45,455. 1 1 P. G. Gassman, S. M. Bonser and K. Minaric-Majerski, J. Am. Chem. Soc., 1989, 111,2652. 12 K. C. Nicolaou, G. Zuccarello, Y. Ogawa, E. J. Schweiger and T. Kumazaura, J. Am. Chem. SOC.,1988,110,4866; K. C. Nicolaou, G. Zuccarello, C. Riemer, V. A. Estavez and W.M. Dai, J. Am Chem. SOC.,1992, 114, 7360. 13 P. A. Wender, M. Harmata, D. Jeffrey, C. Mukai and J. Suffert, Tetrahedron Lett., 1988,29,909. 14 R. K. Boeckman, S. K. Yoon and D. K. Heckendorn, J. Am. Chem. SOC.,1991, 113,9682. 15 F. G. Bordwell and G. D. Cooper, J. Am. Chem. SOC.,1951,73,5187. 16 N. P. Neurieter and F. G. Bordwell, J. Am. Chem. SOC.,1963, 85, 1209; N. P. Neurieter, J. Am. Chem. Soc., 1966,88,558;N. Tokura, T. Nagai and S. Matsumura, J. Org. Chem., 1966, 31, 349; F. G. Bordwell, J. M. Williams, E. B. Hoyt and B. B. Jarvis, J. Am. Chem. Soc., 1968,90,429. 17 N. H. Fischer, Synthesis, 1970,393; G. Opitz, K. Rieth and T. Ehlis, Chem. Ber., 1990, 123, 1563, 1989 and references therein. 18 L. A. Carpino, L. V. McAdams, R. H. Rynbrandt and J. W. Spiewak, J. Am. Chem. SOC.,1971, 93, 476; J. C. Philips, J. V. Swisher, D. Haidukewych and 0.Morales, Chem. Commun., 1971,22. 19 Preliminary communication: A. G. Sutherland and R. J. K. Taylor, Tetrahedron Lett., 1989,30,3267. 20 J. Kattenburg, E. R. de Waard and H. 0.Huisman, Red. Trav. Chim. Pays-Bas, 1975,94,89; C. H. Chen, G. A. Reynolds and J. A. van Allan, J. Org. Chem., 1977,42, 2777. 21 G. Gil, Tetrahedron Lett., 1984,25,3805;G. L. Larson and R. Klesse, J. Org. Chem., 1985,50, 3627. 22 R. Noyori, S. Murata and M. Suzuki, Tetrahedron, 1981,37,3899. 23 E. Nakamura, M. Isaka and S. Matsuzawa, J. Am. Chem. SOC.,1988, 110, 1297. 24 G. Casy, A. G. Sutherland, R. J. K. Taylor and P. G. Urben, Synthesis, 1989, 767. 25 S. Friedrich-Bochnitschek, H. Kunz and H. Waldmann, J. Urg. Chem., 1989,54,751 and references therein. 26 Y. Tsuda and Y. Sakai, Synthesis, 1981, 119; A. P. Krapcho, Synthesis, 1982, 805, 893. 27 B. M. Trost and D. P. Curran, Tetrahedron Lett., 1981, 22, 1287; B. M. Trost and R. Braslau, J. Org. Chem., 1988,53,532. 28 E. Eliel, Angew. Chem., Int. Ed. Engl., 1965,4,761; N. G.Franklinand H. Feldkamp, Angew. Chem., Znt. Ed. Engl., 1965,4,774. 29 D. J. Loomes and M. J. T. Robinson, Tetrahedron, 1977,33, 1 149. 30 N. Berenjian, P. De Mayo, M. E. Sturgeon, L. K. Sydnes and A. C. Weedon, Can. J. Chem., 1982,60,425. 31 A. P. Kozikowski and S. H. Hung, J. Org. Chem., 1986,51,3400. 32 International Tables for X-Ray Crystallography, Kynoch Press, Birmingham, England, 1969, vol. IV, pp. 55,99, 149. 33 R. Desiderato and R. L. Sass, Acta Crystallogr., 1967,23,430. 34 Y. Nakano, S. Saito and Y. Morino, Bull. Chern. SOC.Jpn., 1970,43, 368; H. Kim, J. Chem. Phys., 1972,57, 1075. 35 D. R. Coulson, Inorg. Synth., 1972,13, 121. Paper 3/02604C Received 6th May 1993 Accepted 24th May 1993

ISSN:1472-7781    

DOI:10.1039/P19930002317

出版商:RSC    

年代:1993

数据来源: RSC