摘要:

2263Acyl Anion Equivalents: Synthesis of Ketones and Enones from a-Phenylthioalkylphosphine OxidesBy J. Ian Grayson and Stuart Warren, University Chemical Laboratory, Lensfield Road, Cambridge CB2 1 EWThe sulphenylated phosphine oxides Ph,P(0)*CH(SR2) R1, easily prepared from triphenylphosphine, diphenyl ordimethyl disulphide, and an alkyl halide, form anions which act as acyl anion equivalents. Reaction with aldehydesand ketones gives vinyl sulphides, which can be hydrolysed to carbonyl compounds. Reaction with a-phenylthio-and cc-methoxy-aldehydes and ketones gives enone precursors. The scope and limitations of the method are des-cribed.CONVENTIOKAL ketone syntheses involve the addition of ponding to this approach. Recently a new family ofa carbon nucleophile (Grignard reagent, enolate anion, ketone syntheses has been evolved using the sameetc.) to a carbon electrophile (usually an acyl derivative), disconnection but with umpolung [equation (ii)] sothe electrophilic carbon atom becoming the new carbonyl that the new carbonyl carbon atom is derived from thecarbon*2 Equation (i) shows the disconnection ‘Orre’- 2 D, p.N. Satehell, K. S . Satehell, M, Cais, and A, Mandel-baum in ‘ The Chemistry of the Carbonyl Group,’ ed. S. Patai,Wiley, London, 1966, pp. 233-330. Preliminary communication, P. Blatcher, J . I. Grayson, andS. Warren, J.C.S. Chern. Comm., 1976, 547. D. Seebach and M. Kolb, Chem. and Ind., 1974, 687J.C.S. Perkin I 2264nucleophilic carbon of an acyl anion eq~ivalent.~ Inthe best known of these, the anion is stabilised by two0 0R+C-R/ II + R+ +-c--R' II ( i i )sulphur atoms, as in dithians (l), and bis(pheny1thio)-methane1j6 (2).Others in this class contain onephosphorus and one sulphur atom [e.g. (3)] and reactwith carbonyl compounds by the Wittig reaction to givevinyl sulphides (4) which can be hydrolysed to ketonesThese differ from the dithian routes in that a 1,2-alkylative carbonyl transposition is involved, the finalcarbonyl carbon atom coming from what was originallyan sp3 carbon atom, and the carbonyl carbon atom of(5) -the electrophile ( RZCHO) becoming a saturated carbonin the product. Green originally used the anion fromdiethyl methylthiomethylphosphonate (3 ; R1 = H) asan acyl anion equivalent, and this method was developedby Corey and Shulman and others.l09l1 Modificationsusing phosphonium salts 12-15 (6) and phosphonate esterssubstituted with methyl- and phenyl-~ulphinyl,~~9~7 andphenylsulphonyl 17-19 (7) groups have been used inattempts to solve the three main problems of the method :(i) lack of a good general synthesis of the sulphur-containing Wittig reagents [the reagents (3) have to beobtained from (3; R1 = H) 73; (ii) poor yields in theWittig reaction, particularly with ketones; 799310 and* We have also developed ketone syntheses from methoxy-alkyldiphenylphosphine oxides uia en01 ethers : C. Earnshaw,C.J. Wallis and S. Warren, J.C.S. Chem. Comm., 1977, 314.0. W. Lever, Tetrahedron, 1976, 32, 1943; B.-T. Grobel andD.Seebach, Synthesis, 1977, 357.5 D. Seebach, Synthesis, 1969, 17; D. Seebach and E. J .Corey, J . Org. Chem., 1975, 40, 231.E. J . Corey and D. Seebach, J . Org. Chem., 1966,31,4097.E. J. Coreyand J. I. Shulman, J . Org. Chem., 1970, 35, 777. * B. M. Trost, K. Hiroi, and S. Kurozumi, J . Amer. Chem. SOC.,1975, 97, 438; B. M. Trost and K. Hiroi, ibid., p. 6911.M. Green, J . Chem. SOC., 1963, 1324.lo I. Shahak and J. Almog, Synthesis, 1969, 170; 1970, 145.l1 H. M. McGuire, H. C. Odon, and A. R. Pinder, J.C.S.T. Mukaiyama, S . Fukuyama, and T. Kumamoto, Tetra-Perkin I , 1974, 1879.hedron Letters, 1968, 3787.l3 I. Vlattas and A. 0. Lee, Tetrahedron Letters, 1974, 4451.(iii) difficulties in converting the vinyl sulphides intocarbonyl compounds.2oFor most applications in synthesis, the diphenyl-phosphinoyl (Ph2PO) group is superior to the triphenyl-phosphonium (Ph3P+) and the dialkoxyphosphinoyl[(RO),PO] groups in that the reagents are usuallycrystalline, reactivity and yields are higher, and separ-ation of the Wittig reaction by-product, diphenyl-phosphinic acid, is very simple. We have thereforedeveloped methods for ketone and enone synthesis usingthe Ph,PO group in combination with the PhS or MeSgroups * which have to a certain extent solved the threeproblems above. Our interest in these compounds arosefrom our work on Ph,PO 21 and PhS 22 rearrangements,since either group might rearrange from the inter-mediate (15) .23Preparation of the Horner-Wittig A cyl Anion Equiva-lents.-Primary alkyldiphenylphosphine oxides (8) arereadily available from triphenylphosphine via alkylationand hydrolysis 21*24 (Scheme 1).The anions from thesecompounds, formed with n-butyl-lithium in the presenceTABLE 1Synthesis of Horner-Wittig acyl anion equivalents (9)and (10)Yield (%)Method R1B H c MeA E tA PriA PhCH, c PhCH,A PhSR 2 = Ph R2 = Me96 8669 7573 6281 78798475of tetramethylethylenediamine (TMEDA), react readilywith dimethyl or diphenyl disulphide to give thesulphenylated phosphine oxides (9) in high yield (Table 1)l4 G. Wittig and M. Schlosser, Chem. Ber., 1961, 94, 1373.l5 H. J. Bestmann and J. Angerer, Annulen, 1974, 2085.l6 M. Mikolajczyk, S. Grzejszczak, and A. Zatorski, J . Urg.l7 M.Mikolajczyk, S. Grzejszczak, W. Midura, and A. Zatorski,I. C. Popoff, J. L. Dever, and G. R. Leader, J . Urg. Chem.,G. H. Posner and I>. J. Brunelle, J . Org. Chem., 1972, 37,2o A. J . Mura, G. Majetich, P. A. Grieco, and T. Cohen,21 A. H. Davidson, C. Earnshaw, J . I . Grayson, and S. Warren,22 P. Brownbridge and S. Warren, J.C.S. Perkin I , 1977, 1131.23 J. I. Grayson and S. Warren, submitted to J.C.S. Perkin I .24 L. Horner, H. Hoffmann, and H. G. y p p e l , Chem. Ber.,1958, 91, 64; K. ,Sasse in Houben-Weyl, Methoden der Or-ganischen Chemie, Thieme, Stuttgart, 1963, vol. 1211, pp. 144-150.Chem., 1975, 40, 1979.Synthesis. 1975, 278.1969, 34, 1128.3547.Tetrahedron Letters, 1975, 4437.J.C.S. Perkin I , 1977, 14521977 2265(absence of TMEDA leads to considerably lower yields).This route gives poor yields for R1 = HI as the initialproduct (10; R2 = Ph) is further sulphenylated underthe reaction conditions to give a mixture of (10; R2 =Ph) and the bis(pheny1thio)-compound (1 1).Pure (1 1)can be obtained by sulphenylation of (10; R2 = Ph)prepared by route B. The unsubstituted compounds(10) are made in high yield by the Arbusov reaction(route B in Scheme l), and can themselves be convertedinto substituted compounds [e.g. (9; R1 = Me)] byalkylation (again using BuLi and TMEDA to make theanions-route C, Scheme 1). Previous syntheses ofsulphenylated phosphine oxides have produced only theunsubstituted compounds (10) and use the less readilyavailable starting materials Ph2PH 25 or Ph2PLi.26 Allof the reagents (9) are stable crystalline compounds whichcan be purified and stored without special precautions.Reactions of the Horner-Wittig Acyl Anion Equivalents(9) with Aldehydes (Scheme 2).-The sulphur atom on thea-position increases the stability of the anion (12) sothat the first stage of the Horner-Wittig reaction to givethe adduct (13) is slower.By contrast the second stage,(13) + (14), is faster, since the transition state (16)1, BuLi, TMEDA(9)f r /(10)$ = Ph 1, BuLi, TMEDA2. PhSSPh IPh*QPhSPh(11)SCHEME 1has a partial negative charge on the a-carbon, enhancingthe rate of P-C bond cleavage. Horner-Wittig re-actions using the Ph2P0 group normally give adductsanalogous to (15).21 These can be isolated at roomtemperature without completion of the Wittig reaction* Similar results have been observed with other phosphineoxides: B.Lythgoe, T. A. Moran, M. E. N. Nambudiry, and S.Ruston, J . C . S . Perkin I, 1976, 2386; M. Schlosser and H. B.Tuong, Chimia (Switz.), 1976, 30, 197.to the olefin, which generallypotassium base. However, withrequires a sodium ora sulphur atom present,!? .R1(12)R3CH0 - 78OC I fl ‘ dOH 3/ ‘OLi( 1 5) (13)IheatCHR3( 1 7 ) (14)ii (-1,~‘I !I P h2P - - +-SR(16)SCHEME 2warming the reaction mixture to room temperature for0.5 h is enough to cause completion of the Wittig reaction(13) (14) * (Table 2). The adducts (15) may beTABLE 2Synthesis of vinyl sulphides from phosphine oxides (9)and aldehydesYield(Yo) Yieldof (%Ivinyl ofK1 KZ R3 (14) (17)2.PhCH, Ph n-Hexyl 93 933. PhCH, Ph Ph 90 974. Pri Ph p-MeO-C,H, 94 865. Pri Ph PhCHXH 93 a6. H Ph 3,4- (CH,O,)C,H3 92 asulphide ketone1. E t Ph Ph 93 78a Could not be hydrolysed by conventional methods; seetext.isolated by quenching with aqueous ammonium chlorideimmediately after the addition of the aldehyde atReactions of the Horner-Wittig Acyl Anion Equivalents-78 0C.23z5 H. Hellmann and J . Bader, Tetrahedron Letters, 1961, 724.26 A. M. Aguiar, K. C. Hansen, and J . T. Mague, J . Org. Chem.,1967, 32, 23832266 J.C.S. Perkin I(9) with Ketones.-One of the problems with phosphorus-containing acyl anion equivalents is their lack of re-activity in the Wittig reaction with ketones.Pre-sumably the extra stability given to the anion (12) bythe sulphur atom allows the sterically favourableabstraction of an a-proton to be the major reaction.Our alkylated reagents (9; R2 = Ph) did not giveHorner-Wittig products with ketones : for example thephosphine oxide (9; R1 = Et, R2 = Ph) was unchangedwhen treated with cyclohexanone or acetophenone usingsodium or lithium bases.The unsubstituted PhS reagents (9; R1 = H, R2 =Ph) did react with ketones and gave excellent yields ofthe vinyl sulphides (18) (Table 3). The substitutedreagents also react with ketones if a methylthio insteadof phenylthio group is present (9; R1 = alkyl, R2 = Me)and the substituent (R1) is not branched (Table 3).Thus while (9; R1 = Me, Et, R2 = Me) gave goodTABLE 3Synthesis of vinyl sulphides from phosphine oxides (9)and ketonesYieldofvinylsulphide(%)K3 K4 (18) K' K21.E t Yh Ph Me a u90 3. H Yh Ph Me - 9072 b4. H Ph [CHzI 55. Me Me PhCH, Me - 6. Pri Me [CHzI 5 a7. E t Me P h Me a8. E t iMe [CHZI 5 63starting material consumed.U 2 . E t Yh [CHZI 5 - a No reaction. Yield of ketone (19), 60:/,. Based onYield of ketone (19) 600/.yields of vinyl sulphides with ketones, (9; R1 = Pri,R2 = Me) did not react. In fact (9; R1 = Et, R2 =Me) was unchanged when treated with the very readilyenolisable ketone acetophenone, a point also noted by* Hydrolysis with TFA is mentioned also by R. C. Cookson andP. J . Parsons, J.C.S. Chem.Comm., 1976, 990.27 S. Weiland and J. F. Arens, Rec. Trav. chim., 1960, 79, 1293.28 T. Mukaiyama, K. Kamio, S. Kobayashi, and H. Takei,29 T. Mukaiyama, M. Shiono, and T. Sato, Chem. Letters, 1974,30 K. Geiss, B. Seuring, R. Pieter, and D. Seebach, Angew.31 B. S. Kupin and A. A. Petrov, Zhur. org. Khim., 1967, 3, 97532 A. S. Kende, D. Constantinides, S. J. Lee, and L. Liebeskind,Bull. Chem. SOC. Japan, 1972, 45, 3723.37.Chem. Internat. Edn., 1974, 13, 479.(Chem. Abs., 1967, 67, 99786).Tetrahedron Letters, 1975, 405.Corey.' We are therefore still unable to make ketonesbranched on both sides of the carbonyl group by thesemethods. Ketones branched on one side can be madeeither by treating a branched reagent (9; R1 = secondaryalkyl) (Table 2) with an aldehyde, or an unbranchedreagent (9; R1 = primary alkyl, R2 = Me) (Table 3)with a ketone.Hydrolysis of Vinyl Su1phides.-The very multiplicityof methods available for this deceptively simple step[i.e.(18) to (19)] shows how troublesome it can be. Themain methods are those based on m e r c ~ r y , ~ , ~ ~ ~ ~ ort i t a n i ~ m , ~ ~ , ~ ~ and the acid-catalysed addition of thiolsfollowed by hydrolysis of the t h i o a ~ e t a l . ~ ~ ~ ~ ~ Otherworkers have used various acids without heavy metal~ a 1 t s . l ~ ~ ~ ~ ~ ~ ~ Most of the vinyl sulphides we have madecan be hydrolysed simply and in high yield by dissolvingthem in chloroform containing trifluoroacetic acid(TFA) and working up with aqueous sodium carbonate.*This method gives poor results for the vinyl sulphides ofaldehydes (18; R1 = H) for which the HC1-catalysedaddition of PhSH is better.20 However, even thismethod fails for aldehyde derivatives where the doublebond is stabilised by conjugation with an aromaticsystem (e.g.entry 6, Table 2). Vinyl sulphides ofaldehydes have also been hydrolysed to the correspond-ing 2-phenylthio-a1deh~des.l~ The only reported hydro-lyses of dienyl sulphides to enones have been to giveA4-3-oxosteroids.33 All the methods we tried with onediene (entry 5 , Table 2)-TFA, HgCI,, TiCI,, HCl inMeOH-gave either unchanged starting material or un-characterised decomposition products. There is clearlystill a need for a more reliable general method for vinylsulphide hydrolysis.Enone Synthesis .-The hydrolysis of or,y-bis( met hyl-thio)- and -(phenylthio)-ally1 compounds [e.g. (21)] toenones r e g .(22)] has been reported where R2 = Me 34or Ph.35 The bis(pheny1thio)allyl compounds are alsosynthetically useful as ' reverse Michael equivalents '(23).35 These compounds could obviously be made fromour reagents (9) providing that they would react with thea-phenylthiocarbonyl compounds (20) and that thelatter are available. We have already reported 36 aregiospecific and convergent synthesis of a-phenylthio-ketones from bis(pheny1thio)-compounds (24) and wehave now found that a-phenylthio-aldehydes may bemade from the readily available a-phenylthio-esters (25)by reduction 37 to the alcohol (26) and oxidation withCorey 's pyridinium chlorochromate reagent .381,3-Bis(phenylthio)allyl ethers (21) can be prepared33 S.Bernstein and L. Dorfman, J . Amer. Chem. SOC., 1946,68,1152; G. Rosenkranz, S. Kaufmann and J. Romo, ibid., 1949,71,3689.34 E. J . Corey, B. W. Erickson, and R. Noyori, J . Amer. Chem.SOC., 1971, 93, 1724.35 T. Cohen, D. A. Bennett, and ,4. J . Mura, J . Org. Chem.,1976, 41, 2506.36 P. Blatcher and S. Warren, J.C.S. Chem. Comm., 1976, 1055.37 P. Brownbridge, I . Fleming, A. Pearce, and S. Warren,38 E. J . Corey and J. W. Suggs, Tetrahedron Letters, 1975,J.C.S. Chem. Comm., 1976, 751.26471977 2267by our route in godyields (Table 4) on the basis ofstarting material consumed. Corey 34 made lJ3-bis-(methy1thio)propene by the Wittig reaction of diethylR3 R3TsOHbenzenePhS PhS OHR4' (24)L i A l Hi, phs< pyridinium-OH c h l o r o -- L( 2 5 )chromate( 2 6 ) (20; R4 = H)metli ylt hiorne t liylphosphonate and (met hylthio) acet-aldehyde, but achieved only 31(y0 yield.We reasoned(10; R2 = Ph)( 2 7 )in much higher overall yield the a,y-bis(pheny1thio)allylcompound (29) already prepared (Table 4, entry 3).TABLE 4Synthesis of eiioiie precursors (2 1) from ol-phenylthio-carbonyl compounds (20)Yield ConversionK1 R3 R4 (%I (Yo)1. H Yh Et H 76 482. Et Ph E t H 68 353. H Ph Me Mt: 76 514. H Ph Me Me 93 93Based on starting material consumed. Overall yieldvia (28).Retrosynthetic Analysis 40 of thc Routes to Ketones andEnones.-These ketone syntheses [equation (iii)] clearlybelong to the acyl anion family, but the acyl anionfragment can be derived either from an entire alkylhalide or by alkylation of the one-carbon unit (10).Themethod is iterative as the carbonyl fragment can itselfbe made by the same reaction sequence.The enones are also derived from carbonyl compoundsand alkyl halides; here the disconnections are thoseshown in equation (iv). This is in contrast to Cohen'senone e q u i ~ a l e n t , ~ ~ where the starting material is itselfan enone (30). After conversion into the a,y-bis(pheny1-thio)allyl compound, and alkylation, hydrolysis gives theenone (31) functionalised at the y-position. As thestarting enone may be obtained by an aldol-type con-densation, the disconnections corresponding to Cohen'sthat a l,%disubstituted ally1 system could be made moreconveniently by using a starting ketone with a lessacidic a-hydrogen atom.The a-methoxy-ketone (27) 39reacted in very high yield with the phosphine oxide (10;R2 = Ph) to give the oc-phenylthio-y-methoxyallyl com-pound (28), which underwent ready substitution onPhS PhSR3CH0heating with benzenethiol and a catalytic amount oftoluene-$-sulphonic acid monohydrate (TsOH) , giving3Q I). Guillerm-Drom, M. L. Capmau, and W. Chodkiewicz,40 I. Fleming, ' Selected Organic Syntheses,' London, Wiley,Bull. SOC. chim. France ( B ) , 1973, 1417.1973, pp. 1-6; E. J. Corey, Pure AppZ. Chem., 1967,14, 19.YOMe - k SPhroute are those shown in equation (v). 'I'he two enonesyntheses are thus complementary.Though we have in fairness emphasised the difficultieswe found with some classes of compound, we believethat this route offers one of the easiest and highestyielding convergent routes to ordinary ketones that is atpresent available.EXPERIMENTALGeneral procedures have been described elsewl~ere.~~N.m.r.signals marked with an asterisk belong to diastereo-topic groups of protons. TFA refers to trifluoroaceticacid, TMEDA to tetramethylethylenediamine, THF totetrahydrofuran (distilled from lithium aluminium hydride),and petrol to light petroleum (b.p. 60-80 "C). Reactionswith butyl-lithium were carried out under nitrogen.Diphenyl(fihenyZthiometlzyZ)fihosphine Oxide 25 ( 10 ; Ii2 =41 A. H. Davidson, I.Fleming, J. I. Grayson, A. Pearce, R. L.Snowden, and S. Warren, J.C.S. Perkin I, 1977, 5502268 J.C.S. Perkin IPh) .--rWethod B. Ethyl diphenylpliosphinite 42 (24 g) andchloromethyl phenyl sulphide 43 (17.5 g) were heatedtogether under nitrogen a t 150 "C for 1.5 h. On cooling, asolid separated, which was recrystallised from ethylacetate-petrol to give the phosphine oxide (32.5 g, 96y0),m.p. 106-107 "C (lit.,25 101-102 "C), RF (EtOAc) 0.40,T (CDCI,) 2.1--2.9 (15 H, m, Ph,P and PhS) and 6.27 (2 H,d, J=p 9 Hz, CH,P), m/e 324 (M', 420/,), 279 (Ph,POH,18), and 201 (Ph,PO, 100).DiphenyZ(methylthiomethyl)phosphine Oxide 259 26 ( 10 ;R2 = Me).-Reaction of ethyl diphenylphosphinite 42 (10.6g) and chloromethylmethyl sulphide (4.55 g) (method B)gave the phosphine oxide (10.4 g, 86y0), m.p.139-140 "C(from EtOAc-petrol) (lit.,25 139-140 "C), RF (EtOAc) 0.20.Spectra agree with those reported.26Diphenyl-l-(phenyEthio)ethylphosphine Oxide (9 ; R1 =Me, R2 = Ph) .-Method C. Diphenyl(phenylthiomethy1)-phosphine oxide (0.7 g, 2.2 mmol) in dry THF (30 ml) and1- (Methylthio)ethyktipkenylp~Losphine Oxide (9; R1 =1X2 = Me) .-Reaction of (methylthiomethy1)diphenylphos-phine oxide (2 g, 7.6 mmol), n-butyl-lithium (4.6 ml; 1 . 8 ~in hexane), TMEDA (1.15 ml, 8.3 mmol), and methyl iodide(0.52 ml, 8.3 mmol) (method C) gave a pale yellow solid.Recrystallisation (ethyl acetate-petrol) gave the phosphineoxide (1.57 g, 75y0), m.p. 122-123 "C, RF (EtOAc) 0.30,Y, (CHCI,) 1 440 (PPh) and 1 185 c1n-l ( P O ) , T (CDC1,)2.0-2.7 (10 H, m, Ph,P), 6.76 (1 H, quint, JHp = JHH =7.5 Hz, MeCHP), 7.93 (3 H, s, MeS), and 8.50 (3 H, dd,JHp 15, JHH 7.5 Hz, CH,CHP), rnle 276 (Ill', lo%), 230(M - MeSH, loo), and 202 (Ph,POH, 85%) (Found: C,64.9; H, 6.1; P, 11.0.Cl,Hl,OPS requires C, 65.2; H,6.2; P, 11.2yo).Diphenyl-l-(phenylthio)propylphosp~~ine Oxide (9 ; Ti1 =Et, It2 = Ph) .--Method A . Diphenylpropylphosphineoxide 41 (1.5 g, 6.1 mmol) in dry THF (40 ml) and TMEDA(0.93 ml, 6.7 mrnol) was treated with n-butyl-lithium0 R ~ C H OSPhPhS Q 0(30) Q- SPhSPh 1, EuLiHM PA2 , R3Xc___cTMEDA (0.35 ml, 2.5 mmol) was treated with n-butyl-lithium (1.05 ml; 2.4111 in hexane) at -78 "C. The orangeanion was quenched after 0.2 h with methyl iodide (0.16 ml,2.5 mmol) and the resulting pale yellow solution wasallowed to warm to room temperature over 0.5 h.Aqueousammonium chloride (40 ml) was added, and the productextracted with chloroform (3 x 30 ml). The organicextracts were washed with dilute hydrochloric acid (20 ml),dried (MgSO,) , and evaporated to give a pale yellow solid.Recrystallisation (ethyl acetate-petrol) gave the phosphineoxide (490 mg, 69%), m.p. 154-155 "C, (EtOAc) 0.41,vmaX. (CHCI,) 1 580, 1 480 (PhS), 1 440 (PhP), and 1 180cm-l ( P O ) , z 2.0-2.6 (10 H, m, Ph2P), 2.8 ( 5 H, m, PhS),6.62 (1 H, dq, J H p 9 Hz, JHH 7.5 Hz, MeCHP), and 8.46(3 H, dd, J H p 15 Hz, JHH 7.5 Hz, CH,CHP), m/e 338 (M',25y0), 279 (Ph,POH, 22), 202 (Ph,POH, loo), 201 (Ph,PO,50), 138 (PhSEt, 80), and 110 (PhSH, 50) (Found: C, 71.2;H, 5.95; P, 9.35.C2,Hl,0SP requires C, 71.0; H, 5.65;P, 9.15%).qR3-S PhqR30(31 1(2.8 ml; 2 . 4 ~ in hexane) a t -78 "C. After 0.2 h theorange anion was added to a solution of diphenyl disulphide(1.37 g, 6.3 mmol) in dry THF (30 ml) a t -78 "C and theresulting pale yellow solution was quickly worked up withaqueous sodium carbonate. The product was extractedwith chloroform (3 x 30 ml) and the organic extracts werewashed with dilute hydrochloric acid (20 ml) and saturatedbrine (20 ml), dried (MgSO,) , and evaporated. Recrystallis-ation from cyclohexane gave the phosphine oxide (1.59 g,73y0), m.p. 140-141 "C, Rp (EtOAc) 0.41, vmax. (CHC1,)1580, 1480 (PhS), 1438 (PhP), and 1175 cm-l (P=O),T (CI>CI,) 2.0-2.7 (10 H, m, Ph,P), 2.85 (5 H, s, PhS),m, CH,), and 8.79 (3 H, t, JHH 7 Hz, CH,CH,), m / e 352(Ph,POH, loo), 151 ( M - Ph,PO, 97), 109 (PhS, 65), and77 (Ph, 71) (Found: M+, 351.1049.C,,H,,OPS requiresM, 352.1050).l-(MethyZthio)proPyZdifihenylphosPhine Oxide (9 ; R1 =6.49 (1 H, dt, JHH 9.5, J H p 2 Hz, C,H,.CHP), 7.8-8.4 (2 H,(M', 20y0), 279 (Ph,POH, 38), 243 (M - PhS, 45), 20242 P. F. Cann, D. Howells, and S. Warren, J.C.S. Perkin 11, 43 L. W. Fancher, Ger. Pat. 1,112,735 (Chem. Abs., 1962, 56,1972, 304. 11499)1977 2269Et, R2 = Me) .-Diphenylpropylphosphine oxide 41 (3 g,12.3 mmol), n-butyl-lithium (7.8 ml; 1 . 8 ~ in hexane),TMEDA (1.95 ml, 14 mmol), and dimethyl disulphide(1.27 ml, 14 nimol) (method A; work-up with aqueousShl-sodium hydroxide) gave the phosphine oxide (2.22 g,62%), m.p.148-150 "C (from ethyl acetate-petrol),RF (EtOAc) 0.33, vmak (CHC1,) 1 440 (PPh) and 1 180 cm-l( P O ) , T (CIIC1,) 2.0-2.6 (10 H, m, Ph,P), 7.08 (1 H, ddd,JHP 11, JHH 8, 4 Hz, CH,*CHP), 7.9-8.4 (2 €3, m,CH,*CHP) overlain by 7.98 (3 H, s, MeS), and 8.87 (3 H, t,JHH 7 Hz, CH,CH,), m / e 290 (M+, 20%), 244 (Ph,POPr,loo), 229 (Ph,POCH,CH,, 50), 202 (Ph,PO, 96), and 89( M - Ph,PO, 73) (Found: C, 66.2; H, 6.75; P, 10.5.C,,H,,OPS requires C, 66.2; H, 6.6; P, 10.7%).(2-Methyl- 1-pheny1thiopro~yl)diphenylphosphine Oxide (9 ;R1 = Pr i, R2 == Ph) .-Isobutyldiphenylphosphine oxide 41(3 g, 11.6 mmol), n-butyl-lithium (5.2 ml; 2 . 4 ~ in hexane),TMEDA (1.8 ml, 12.5 mmol), and diphenyl disulphide(2.6 g, 11.9 mmol) (method A) gave the phosphine oxide(3.36 g, Sly0), m.p.180-182 "C (from ethyl acetate),(PhP), and 1 175 cm-l ( P O ) , T (CDCl,) 2.0-2.8 (10 H, m,Ph,P), 2.9-3.1 (5 H, m, PhS), 6.42 (1 H, dd, J H P 9, J ~ H3 Hz, CHCHP), 7.4-7.8 (1 H, m, Me,CHCHP), and 8.78and 8.90 (each 3 H, d, JHH 7 Hz, Me,*C), m / e 366 ( M f , 17%),and 165 (M - Ph2P0, 100) (Found: C, 72.3; H , 6.5; P,8.2. C,,H,,OPS requires C, 72.1; H, 6.3; P, 8.45%).(2-Methyl- l-methylthiopropy1)diphenylphosphine Oxide (9 ;R1 = Pri , 11, = Me) .-Isobutyldiphenylphosphine oxide 41(1.5 g, 5.8 mmol), n-butyl-lithium (2.7 ml; 2 . 4 ~ in hexane),TMEDA (0.9 ml, 6.4 mmol), and dimethyl disulphide(0.58 ml, 6.4 mmol) (method A, work-up with aqueous3~-sodium hydroxide) gave the phosphine oxide (1.39 g ,780/,), n1.p.194--195 "C (from ethyl acetate), RF (EtOAc)0.46, v,,,, (CHCI,) 1440 (PhP) and 1 182 cm-l (P=O),JHR 3 Hz, CHCHP), 7.3-7.8 (1 H, m, Me,CHCHP), and8.86 and 9.00 (each 3 H, d, JRH 7 Hz, Me,*C), m/e 304(M+, 7O/,), 258 (M - MeSH, 60), 243 [Ph,P(O).C,H,, 1001,201 (Ph,PO, 70), 103 (M - Ph,PO, 30), and 77 (30)(Found: C , 66.8; H, 7.0; P, 10.35. C,,H,,OPS requiresC, 67.1; H , 6.95; P, 10.2%).Diphenyl-( 2-phenyl- l-phenylthioethy1)phosphine Oxide (9 ;R1 = PhCH,, R2 = Ph).-(a) By sulphenylation. Phen-ethyldiphenylphosphine oxide 44 ( 1 g, 3.3 mmol), n-butyl-lithium (1.5 ml; 2.4111 in hexane), TMEDA (0.5 ml, 3.6mmol), and diphenyl disulphide (0.74 g, 3.4 mmol) (methodA) gave the phosphine oxide (1.07 g, 79y0), m.p.178-179 "C(from ethyl acetate-petrol), RF (EtOAc) 0.40, v,,~,. (CHC1,)1580, 1480 (Ph), 1438 (PhP), and 1175 cm-l (P=O),T (CDCI,) 2.0-2.6 (10 H, m, Ph,P), 2.75 (5 H, s, PhS),2.9-3.5 (5 H, m, Ph), and 6.2-7.3 (3 H, m, PCHCH,),m/e 414 ( M t , 80/,,), 305 ( M - PhS, loo), 212 ( M - Ph,POH,80), and 202 (Ph,POH, 92) (Found: C, 75.0; H, 5.65; P,7.25. C2,H2,0€'S requires C, 75.3; H, 5.6; P, 7.45%).(b) By alkylation. Diphenyl(phenylthiomethy1)phosphineoxide (0.5 g, 1.55 nimol), n-butyl-lithium (0.8 ml; 2 . 4 ~ inhexane) , TMEDA (0.27 ml, 1.9 mmol) , and benzyl bromide(0.23 ml, 1.9 mmol) (method C) gave the same phosphineoxide (0.54 g, 84%).Ris(phenylthio)methyldiphenylphosphine Oxide ( 1 1) .-Di-phenyl(phenylthiomethy1)phosphine oxide (2 g, 6.2 mmol)in dry THF (40 ml) and TMEDA (1 ml, 7 mmol) wastreated with n-butyl-lithium (3.9 ml: 1 . 8 ~ in hexane) atRF (EtOAc) 0.47, v,,,.(CHCl,) 1580, 1480 (PhS), 1440279 (Ph3POH, 53), 257 (M - PhS, 70), 202 (Ph2POH, 85),T (CDC1,) 1.9- 2.6 (10 H, m, PhZP), 7.04 (1 H, dd, .JHp 11,-78 "C. After 0.2 h, the orange anion was added to asolution of diphenyl disulphide (1.55 g , 7 mmol) in dryTHF (30 ml) a t -78 "C, and the resulting pale yellowsolution was quickly worked up with aqueous sodiumcarbonate. The product was extracted with chloroform(3 x 40 ml), and the organic extracts were washed withdilute hydrochloric acid (20 ml), dried (MgSO,), andevaporated to give a white solid. Recrystallisation fromethyl acetate-petrol gave the phosphine oxide (2.0 g, 75%),m.p.152-153 "C, RF (EtOAc) 0.55, vmax. (CHC1,) 1580,1 480 (PhS), 1 440 (PhP), and 1 185 cm-l (P=O), T (CDCl,)2.0-2.6 (10 H, m, Ph,P), 2.8 (10 H, s, PhS), and 5.14(1 H, d, JHp 10 Hz, CHP), m / e 432 (M', 12%), 323 (M -PhS, 48), 231 (M - Ph,PO, loo), 201 (Ph,PO, 42), 199(PhSCHPh, 40), and 109 (PhS, 80) (Found: C, 69.1; H,4.9; I), 6.9. C,,H,,OPS, requires C, 69.4; H, 4.9; P,7.15%).l-Phenyl-2-phenylthiobut-l-ene (14; R1 = Et, R2 = R3 =Ph) .-Diphenyl- l-(pheny1thio)propylphosphine oxide (300mg, 0.85 mmol) in dry THF (30 ml) was treated withn-butyl-lithium (0.56 ml; 1 . 8 ~ in hexane) at -78 "C for0.2 h. The yellow anion was quenched with benzaldehyde(0.1 ml, 1 mmol) t o give a colourless solution which wasallowed to warm to room temperature during 0.5 h. Athick white precipitate formed (diphenylphosphinic acid)which was dissolved by the addition of aqueous ammoniumchloride (20 ml), and the product was extracted withchloroform (3 x 30 ml).The organic extracts were dried(MgSO,) and evaporated, and the resulting oil was purifiedby preparative t.1.c. (CH,Cl,) to give a 4 : 3 mixture ofgeometric isomers of the vinyl sulphide (190 mg, 93y0), asan oil, RF (CH,CI,) 0.77, vmax. (CHC1,) 1610 (C=C), 1600,1580, and 1490 cm-l (Ph), T (CDCI,) 2.4-2.9 (10 H, m,Ph and PhS), 3.20 and 3.30 (1 H, two s, ratio 3 : 4, CH=C),7.54 and 7.68 (2 H, two q, J 7 Hz, MeCH,C=C), and 8.78and 8.85 (3 H, two t, J 7 Hz, Me), m / e 240 (M+, 80), 165(M -- EtCS, 42), 106 (PhEt, loo), and 78 (73) (Found:M+, 240.0965.l-Pheutyl-2-phenylthionon-2-ene (14; R1 = PhCH,, R2 =Ph, R3 = n-C,H,,).-By a method similar t o that describedabove, diphenyl- (Z-phenyl- l-phenylthioethy1)phosphineoxide (0.4 g, 0.97 mmol), n-butyl-lithium (0.5 ml; 2 .4 ~ inhexane), and n-heptanal (0.14 ml, 1.1 mmol) gave an oil,which after preparative t.1.c. (CH,Cl,) gave a 2 : 1 mixtureof geometric isomers of the vinyl sulphide (280 mg, 93%)as an oil, RF (CH,Cl,) 0.77, Y,,,. (CHCI,) 1580, 1490 (Ph),and 1 470 cm-l (PhS), T (CDC1,) 2.6-3.0 (10 H, m, PhS andPh), 3.98 and 4.10 (1 H, t, J 8, and t, J 7 Hz, CH,-CH=C),6.43 and 6.52 ( 2 H, two s, ratio 1 : 2, PhCH,), 7.5-7.9(2 H, m, ally1 CH,), 8.4-8.9 (8 H , m, [CH2],), and 9.0-9.2(3 H, m, Me), m/e 310 ( A f t , 43%), 239 (M - C,H,,, 14),129 (C,H,,CS, loo), and 109 (PhS, 47) (Found: M+,310.1746.C,,H,,S requires M , 310.1754).1,3-Diphenyl-2-phenylthio~ro~ene (14; R1 = PhCH,,R2 = R3 = Ph).-In the same way, diphenyl-(2-phenyl-l-phenylthioethy1)phosphine oxide (0.4 g, 0.97 nimol),n-butyl-lithium (0.46 ml, 1.1 mmol) and benzaldehyde(0.11 ml, 1.1 mmol), gave an oil, which after preparativet.1.c. (CH,Cl,) gave a 3 : 1 mixture of geometric isomers ofthe vinyl sztlphide (261 mg, go%), m.p. 60-63 "C, RF(CH,Cl,) 0.85, v,,,~. (CHC1,) 1 600, 1580, 1490 (Ph), and1470 cm-l (PhS), T (CDCl,) 2.4-3.0 (15 H, m, Ph andCl,Hl,S requires M , 240.0972).44 J. I. Grayson, H. K. Norrish, and S. Warren, J.C.S. Perkin I,1976, 25562270 J.C.S.Perkin IPhS), 3.18 and 3.27 (1 H, two s, CHIC), and 6.21 and 6.44(2 H, two s, ratio 3 : 1, PhCH,), m/e 302 (M+, 36y0), 214(PhCHCH,SPh, 63), and 123 (PhSCH,, 100) (Found: M+,302.1146. C,,H,,S requires M, 302.1128).1 - (p-Methoxyphenyl) -3-methyl-2-phenylthiobut- l-ene ( 14 ;R1 = Pr i, R2 = Ph, R3 = P-MeOC,H,) .-In the sameway, (2-methyl- l-phenylthiopropy1)diphenylphosphineoxide (0.6 g, 1.65 mmol), n-butyl-lithium (0.75 ml; 2 . 4 ~in hexane), and p-methoxybenzaldehyde (0.22 ml, 1.8mmol) gave an oil, which after preparative t.1.c. (CH,Cl,)gave a 1 : 1 mixture of geometric isomers of the vinylsulphide (436 mg, gay0), as an oil, RF (CH,Cl,) 0.73, vnlnx.(CHC1,) 1 600, 1 580, 1 500 (Ph), and 1 250 cm-l (MeO),z (CDC1,) 2.4-3.2 (9.5 H, m, aryl H and CH=C of oneisomer), 3.6 (0.5 H, s, CH=C of other isomer), 6.24 and6.26 (3 H, two s, 1 : 1 ratio, MeO), 6.65 and 7.4 (1 H, twoseptets, J 7 Hz, Me,CH), and 8.80 (6 H, d, J 7 Hz, Me,C),rn/e 284 (M', loo%), 175 ( M - PhS, 8 5 ) , and 160 ( M -PhS - Me, 47) (Found: Mt, 284.1224.Cl,H2,0S requiresM , 284.1235).5-Methyl-1-p?~enyl-4-phenylthiohexa-l,3-diene ( 14; Iil =p r i , R2 = Ph, R3 = PhCH=CH).-In the same way(2-niethyl- l-plienylthiopropyl) diphenylphosphine oxide (0.7g, 1.9 mmol), n-butyl-lithium (0.19 ml; 2 . 4 ~ in hexane),and cinnamaldehyde (0.26 ml, 2.1 mmol) gave an oil, whichafter preparative t.1.c. (CH,Cl,) gave a 2 : 1 mixture ofgeometric isomers of the dienyl sulphide (496 mg, 93%), asan oil, Rp (CH,Cl,) 0.79, vmax.(CHCl,) 1 650, 1610 (C=C),and 1 580 and 1 480 cm-' (Ph), T (CDCl,) 2.4-3.1 (11 H, m,Ph, and PhCH=CH-CH=C), 3.52 and 4.02 ( 1 H, d, J 10,and d, J 1 1 Hz, PhCHECH-CH=C), 3.55 and 3.69 (1 H, d ,J 16, and d, J 1.5 Hz, trans-PhCH-CH), 6.68 and 7.47 ( 1 H ,two septets, J 7 Hz, ratio 1 : 2, Me,CH), and 8.76 and 8.83(6 H, two d, J 7 Hz, Me,C), m/e 280 ( M i , goyo), 203 ( M -Ph, 35), 170 ( M - PhSH, 80), 155 (M - PhSH - Me,loo), and 91 (60) (Found: M ' , 280.1280. C1,W,,S requiresM , 280.1285).R1 = H, R2 = Ph, R3 = 3,4-(CH202)C6H,].-h the sameway diphenylphenylthiomethylphosphine oxide (0.7 g,2.16 mmol), n-butyl-lithium ( 1 ml; 2 . 4 ~ in hexane), andpiperonal (0.36 g, 2.4 mmol) gave an oil, which afterpreparative t.1.c. (CH,Cl,) gave a 4 : 1 mixture of geometricisomers of the vinyl sulphide (507 mg, 92y0), as an oil,RF (CH,Cl,) 0.77, T (CDCl,) 2.6-2.9 ( 5 H, m, PhS), 3.2-3.7( 5 H, m, aryl and vinyl H), and 4.16 and 4.18 (2 H, two s,ratio 1 : 4, OCH,O), m/e 256 ( M t , loo%), 149 (62), 121( M - PhSCHZCH, 32), and 110 (PhSH, 28) (Found: Mt,256.0544.C1,Hl,O,S requires M , 256.0557).l-Phenylbutan-2-one ( I 7 ; R1 = E t , R3 = Ph).-1-Phenyl-2-phenylthiobut- l-ene ( 160 mg) was dissolved inTFA (3 ml) and chloroform (3 ml) and stirred at roomtemperature for 0.3 h. The mixture was neutralised withaqueous sodium carbonate and extracted with chloroform(3 x 20 ml) ; the extract was dried (MgSO,) and evaporatedt o give an oil. Bulb-to-bulb distillation gave the ketone(76 mg, 78%), b.p.70-80 "C a t 0.05 mmHg (lit.,45 b.p.230 "C), v,,, (film) 1 710 ( G O ) , 1 600, 1 580, and 1 490cm-l (Ph), T (CDCl,) 2.8 ( 5 H, m, Ph), 6.4 (2 H, s, CH,Ph),1-( 3,4-Methylenedioxyphenyl)-2-phenylthioethene [14;7.6 (2 H, q, J 7 Hz, CH,Me), and 9.0 (3 H, t, J 7 Hz,CH,CH,) .' Handbook of Chemistry and Physics,' ed. R. C. Weast,46 R. B. Dran, P. Decock, and H. Decock-le-Reverend, Compt.C.R.C. Press, Cleveland, Ohio, 1975.r e n d . , 1971.272C. 1664.l-Phenylnonan-2-one (17; R1 = PhCH,, R3 = n-C,H,,).-In a similar way, l-phenyl-2-phenylthionon-2-ene (204mg), TFA (3 ml), and chloroform (3 nil) gave the ketone(133 mg, 93%) after bulb-to-bulb distillation, b.p. 75-80 "C at 0.05 mmHg (lit.,,, 100-104 "C at 0.3 mmHg),vmax. (CHC1,) 1705 cm-l ( G O ) , T (CDC1,) 2.6-3.0 ( 5 H, m,Ph), 6.37 (2 H, s, CH,Ph), 7.60 (2 H, t, J 7.5 Hz, CH,CH,CO),8.3-8.8 (10 H, m, [CH2I5), and 9.16 (3 H, t , J 5 Hz, Me),nz/e 218 ( M f , 50/,), 127 ( M - PhCH,, loo), and 92 (PhCH,,1,3-Diphenyl~roPan-2-one (17; R1 = PhCH,, R3 = Ph).-In a similar way, 1,3-diphenyl-2-phenylthiopropene (204mg), TFA (3 ml), and chloroform (3 ml) gave the ketone(137 mg, 97%), after bulb-to-bulb distillation, b.p 90-100 "C at 0.05 mmHg (lit.,45 112-125 "C at 0.1 mmHg),vmx.(CHC1,) 1 710 ( G O ) , 1 600, 1 580, and 1 480 cm-l (Ph),T (CDC1,) 2.6-2.8 (10 H , m, Ph) and 6.35 (4 H, s, CH,).l-(p-Methoxyphenyl)-3-methylbutan-2-one (17; R1 = P r i,R3 = p-MeO*C,H,) .-In a similar way, l-(P-methoxy-phenyl) -3-methyl-2-phenylthiobut- l-ene (436 mg), TFA(5 ml), and chloroform (5 ml), stirred for 4 h at roomtemperature, gave the ketone (252 mg, 86%), after bulb-to-bulb distillation, b.p.90-100" C at 0.05 mmHg (lit.,d7146-152 "C at 10 mmHg), vmax. (CHCl,) 1 705 (GO), 1 610,1505 (Ph), and 1240 and 1035 cm-l (OMe), T (CDC1,)2.8-3.2 (4 H, q, A,B,, JtIn 8 Hz, separation 26 Hz, aryl H),6.22 (3 H, s, MeO), 6.34 (2 H, s, CH,), 7.50 ( 1 H, sept,J 7 Hz, Me,CH), and 8.92 (6 H, d, J 7 Hz, Me&), rn/e 192( M I , 1OOyo) and 121 (MeO*C,H,CH,, 37) (Found: M f ,192.1150. C13H1,02 requires M , 192.1150).A ttempted Hydrolyses of &Methyl- l-phenyl-4-phenylthio-Jzexa-1,3-diene (14; lil = Pr', R2 = Ph, R3 = PhCHLCH).-The dienyl sulphide (200 nig) was treated under refluxwith concentrated hydrochloric acid ( 1 ml) in methanol(70 ml) for 18 h.Evaporation, and examination of theresidue by t.1.c. and n.m.r. showed no reaction had takenplace. Similarly, heating the dienyl sulphide (249 mg)with mercury(x1) chloride (490 mg) in 3 : 1 acetonitrile-water (20 ml) under reflux for 72 h, gave unchanged dienylsulphide (170 mg, 68% after preparative t.1.c.) as the onlyidentified product. Similarly, stirring the dienyl sulphide(402 mg) with titanium tetrachloride (0.5 ml) in acetonitrile(10 ml) a t room temperature for 5 h, followed by preparativet.1.c. gave only starting material (142 mg, 35%). Thedienyl sulphide (203 mg) dissolved in TFA-chloroform togive a dark red solution. After stirring for 2 h, isolationof the product gave a yellow oil (196 mg), which appeared(n.m.r., t.l.c., i.r.) t o be a mixture of decomposition products.No trace of the expected enone or of starting material wasfound.2-Phenyl-l-phenylthiopropene 29348 (18; R' = H, R2 =R3 = Ph, R4 = Me) .-Diphenyl(phenylthiomethy1)phos-phine oxide (0.7 g, 2.15 mmol), in dry THF (30 ml) wastreated with n-butyl-lithium ( 1 ml; 2 .4 ~ in hexane) a t-78 "C. After 0.2 h, the orange anion was quenchedwith freshly distilled acetophenone (0.28 mg, 2.4 mmol).The mixture was allowed t o warm to room temperature for0.5 h ; a thick white precipitate formed, which was dis-solved by the addition of aqueous ammonium chloride.The product was extracted into chloroform (3 x 30 ml),and the organic extracts were dried (MgSO,) and evaporated47 Knoll, A.G., Ger.Pat. 727 405/1938 (Beilstein, Handbuchder Organischen Chemie, 8, 111, 489).48 I . Kuwajima, S. Sato, and Y. Kurata, Tetrahedron Letters,1972, 737.35)1977 2271to give an oil. Preparative t.1.c. (CH,CI,) gave a 6 : 1mixture of geometric isomers of the vinyl sulphide (436 nig,goyo), as an oil, RF (CH,Cl,) 0.86, T (CDC1,) 2.6-2.9 (10 H,m, Ph,), 3.44 and 3.74 (1 H, two m, ratio 6 : 1, CH=C), and7.77 and 7.80 (3 H, two s, ratio 6 : 1, MeC=C), m/e 226 (M',loo%), 211 ( M - Me, la), 115 (32), and 91 (43).49 ( 18 ; R1 = H, R2 =Ph, R3R4 =- [CH,],).-In the same way diphenyl(pheny1-thiomethy1)phosphine oxide (0.5 g, 1.55 mmol), n-butyl-lithium ( 0 . 7 ml, 1.7 mmol) and freshly distilled cyclo-hexanone (0.18 ml, 1.7 mmol) gave an oil, which afterpreparative t.1.c.(CH,Cl,) gave the vinyl sulphide (284 mg,goy;), as an oil, RF (CH,Cl,) 0.85. Spectroscopic dataagree with those reported.492-MethyZ-3-~nethyltlzio-l-phenylbut-2-ene (18; R1 = 11, =1x4 = Me, l i 3 = PhCH,).-In the same way, l-(methyl-thio)ethyldiphenylphosphine oxide (0.5 g, 1.8 mniol),n-butyl-lithium (0.9 ml; 2 . 4 ~ in hexane), and benzylmethyl ketone (0.28 ml, 2.1 mmol), gave an oil, which afterpreparative t.1.c. (CH,Cl,), gave a 1 : 1 mixture of geometricisomers of the zrinyl sulphide (249 mg, 72%) as an oil,RE' (CH,Cl,) 0.75, vIIIRX. (CHC1,) 1 600 and 1 480 cm-l (Ph),T (CDC1,) 2.8 (5 H , m, Ph), 6.22 and 6.50 (2 H, two s, ratio1 : 1, PhCH,), 7.74 and 7.75 (3 H , two s, MeS), 7.88 and7.94 (3 H, two q, J 1 Hz, MeC=), and 8.04 and 8.30 (3 H,two q, J 1 H z , MeC=), m/e 192 (M', 100~o), 145 ( M - MeS,60), 143 (60), 129 (56), and 91 (35) (Found: M', 192.0967.Cl,Hl,S requires M , 192.0972).(1-iWTethy1thiopropylidene)cycZohexane (18; R1 = Et, R2 =Me, R3R4 I CH,],).-In the same way l-(methylt1iio)-propyldiphenylphosphine oxide (0.7 g, 2.4 mmol), n-butyl-lithium (1.45 nil; 1 .8 ~ in hexane), TMEDA (0.37 ml,2.6 mniol), and freshly distilled cyclohexanone (0.27 ml,2.6 mrnol) gave an oil. Preparative t.1.c. (CH,Cl,) gavestarting material (253 mg, 3604), RP (CH,Cl,) 0.0, and thevinyl sulphide (163 mg, 40% conversion, 63% based onstarting material consumed) as an oil, RF (CH,Cl,) 0.80,vlllaX. (CHC1,) 1 620 cm-l (C=C), T (CDCl,) 7.4-7.6 (4 H, m,CH,-C= on ring), 7.65 (2 H, q , J 7 Hz, =C-CH,Me), 7.87(3 H, s, MeS), 8.47 (6 H, ni, [CH,]J, and 8.96 (3 H, t, J 7 Hz,CH,CH,), nz/e 170 (Mr, 1000/,), 155 (M - Me, 95), 123( M - MeS, 9), and 81 (14) (Found: M', 170.1131.Cl,H18S requires M , 170.11 28).Reaction of Dip henyl- 1 -p henylthioprofiylphosphine Oxidewith Ketone.5.--The phosphine oxide (9; R1 = Et, R2 =Ph) (0.5 g, 1.43 mmol) in dry THF (30 ml) and TMEDA(0.23 nil, 1 6 mmol) was treated with n-butyl-lithium(0.67 ml, 1.6 mmol) a t -78 "C.After 0.3 h, the orangeanion was quenched with freshly distilled cyclohexanone.The resulting pale yellow solution was allowed t o warm toroom temperature for 0.5 h , but no precipitate formed.After work-up in the usual way, starting material was theonly identifiable material obtained.Similarly, no reactionwas observed with acetophenone, or if the reaction wascarried out using n-butyl-lithium a t room temperature, orusing sodium hydride to form the anion.3-Methyl-4-phenylbutan-2-one (19; R1 = R4 = M e, R3 =PhCH,) .-2-Methyl-3-methylthio- l-phenylbut-2-ene (235mg) was stirred with TFA (3 ml) and chloroform (3 ml) forPhenylthiornethylenecyclohexane 29ft This compound has been prepared by a different method and40 F. A . Carey and A. S. Court, J . Org. Chem., 1972, 37, 939.partly charactcrised ; see ref. 15.L. H. Rriggs, G. C. n e Ath, and S. R. Ellis, J . Chem. Soc.,1942, 61.4 h a t room temperature. The mixture was poured intoaqueous sodium carbonate and extracted with chloroform(3 x 30 ml); the organic extracts were dried (MgSO,) andevaporated to give an oil.Bulb-to-bulb distillation gavethe ketone (116 mg), b.p. 120-130 "C a t 0.1 mmHg (lit.,50b.p. 111 "C at 10 mmHg), vnlax. (film) 1710 ( G O ) , 1605,and 1495 cm-l (Ph), T (CDC1,) 2.6-2.9 (5 H, m, Ph), 6.8-7.6 ( 3 H, m, PhCH,CHCO), 7.92 (3 H, s, MeCO), and 8.90(3 H , d, J 7 Hz, CH,CH), rn/e 162 ( M - , 35y0), 147 (1' - Me,21), 119 (144 - MeCO, 18), and 91 (C,H, 100).Cyclohexyl Ethyl Ketone (19; R1 = Et, R3K4 = [CH2I5).-By a method similar to that described above, l-(methyl-t1iio)propylidenecyclohexane (225 nig), TFA (2 ml), andchloroform (2 ml) gave an oil, which after bulb-to-bulbdistillation gave the ketone (108 mg, 60%), b.p.80-90 "Ca t 15 mmHg (Iit.,5l b.p. 88-89 "C a t 19 mmHg), Y,,, (film)1710 cm-l (CEO), T (CDCl,) 7.54 (2 H, q, J 7 Hz, CH,Me),7.6-8.8 (11 H, m, cyclohexyl ring), and 8.96 (3 H, t,J 7 Hz, CH,CH,).2-PhenylthiobutanaZ (20; R3 = Et, R4 = H).-2-Phenyl-thiobutan-1-01 5 2 (0.48 g, 2.6 mmol), and pyridiniumchlorochromate 38 (1.35 g, 6.3 mmol) were stirred a t roomtemperature in dry dichloromethane (50 nil) for 2.5 h.The dark suspension was filtered and the solid washed wellwith ether. The filtrate was evaporated and the residuepurified by preparative t.1.c. (3 : 7 acetone-petrol) to givethe aldehyde 7 (260 mg, 55%), RF (3 : 7 acetone-petrol)0.44, Y,,,. (film) 2 700 (CHO), 1 710 ( G O ) , and 1580 cm-1(PhS), T (CDC1,) 0.72 (1 H, d, J 4 Hz, CHO), 2.6-2.9(5 H, ni, Ph), 6.6 (1 H, dt, J 4, 7 Hz, CH,CHCHO), 8.0-8.6 (2 H, m, CH,*), and 8.95 (3 H, t, J 7 Hz, CH,CH,),mle 180 (M+, 179 ( M - H, 40), 151 (PhSCH,CO,loo), 123 (PhSCH,, 25), and 109 (40).2-Methyl-1,3-bis(~henylthzo)but-l-ene (21 ; R1 = H, R2 =Ph, R3 = R4 = Me).--lXphenyl(phenylthiomethy1)phos-phine oxide (0.7 g, 2.2 mniol) in dry THF (30 1111) and TMEDA(0.35 ml, 2.4 mmol) was treated with n-butyl-lithium (1 ml;2 . 4 ~ in hexane) a t - 78 "C. After 0.2 h, 3-phenylthiobutan-2-one 53 (0.4 ml, 2.4 mmol) was added and the solution wasallowed to warm to room temperature during 0.5 h, givinga white precipitate and a pale yellow solution. Aqueousammonium chloride was added, and the product extractedwith chloroform (3 x 30 ml).The organic extracts weredried (MgSO,) and evaporated t o give an oil. Preparativet.1.c. (CH,Cl,) gave starting material (227 mg, 320/,), and a15: 1 mixture of geometric isomers of the bis(phenyZthio)-olefin (315 mg, 51% conversion, 76% yield based on startingmaterial consumed) as an oil, 2 ? ~ (CH,CI,) 0.75, vmaS, (CHCl,)1585 and 1480 cm-l (PhS), T (CDC1,) 2.5-3.2 (10 H, ni,Ph), 4.10 and 4.20 (1 H, two m, ratio 1 : 15, CH=C), 6.12(1 H, q, J 1 Hz, SCHMe), 8.10 (3 H, ni, MeC=C), and 8.58(3 H , d, J 7 Hz, CH,CH), nz/e 286 (M+, 340/,), 177 ( M -PhS, loo), 149 (PhSC=CMe, 50), 133 (PhSCHZCH, 50), and110 (40) (Found: M', 286.0857. Cl,H18S, requires M ,286.0848).1,3-Bis(phenylthio)penf-l-ene (21; R1 = R4 = H, 1<2 ==Ph, R3 = Et).-In a similar way, diphenylphenylthio-methylphosphine oxide (0.7 g, 2.2 mmol), n-butyl-lithium(1 ml; 2 .4 ~ in hexane), and 2-phenylthiobutanal (0.33 ml,2.4 mmol) gave an oil, which was purified by preparativet.1.c. (CH,CI,) t o give starting material (263 Ing, 380<), andthe bis(phenylthi0)-olejin (295 mg, 48% conversion, 76%51 H. Meerwein, Annalen, 1949, 419, 167.52 P. Brownbridge and S. Warren, following paper.53 E. G. G. Werner, Rec. Trav. chzm., 1949. 68, 5092272yield based on starting material consumed), as an oil,RF (C,H,Cl,) 0.79, v,. (CHC1,) 1 585 and 1480 cm-l (PhS),T (CDC1,) 2.5-3.1 (10 H, m, Ph,), 3.8-4.3 (2 H, m,CH=CH), 6.45 (1 H, q, J 6 Hz, =CHCHCH,), 8.1-8.5 (2 H,m, CH,*CH,), and 8.97 (3 H, t, J 8 Hz, CH,CH,), wt/e 286(M', 13), 177 (M - PhS, loo), 135 (20), and 109 (26)(Found : M', 286.0845. Cl,Hl,S, requires M, 286.0848).3,5-Bis(phenylthio)hept-3-ene (21; R1 = R3 = Et, R2 =Ph, IZ4 = H).-In a similar way, diphenyl-l-(pheny1thio)-propylphosphine oxide (0.35 g, 1 mmol), n-butyl-lithium(0.6 ml; 1 .8 ~ in hexane), TMEDA (0.08 ml, 1.1 mmol),and 2-phenylthiobutanal (200 ma, 1.11 mmol) gave an oil,which was purified by preparative t.1.c. (CH,CI,) to givestarting material (170 mg, 48%) and a 3 : 2 mixture ofgeometric isomers of the bis(pheny1thio)-olefin ( 109 mg,35% conversion, 68% yield based on starting materialconsumed), as an oil, RS7 (CH,Cl,) 0.77, vnlax, (film) 1 620(C=C), 1 580 and 1 475 cm-l (PhS), z (CDC1,) 2.5-2.9 (10 H,m, PhS), 4.30 and 4.44 (1 H, two d, J 10 Hz, ratio 2 : 3,=CHCH), 5.56 and 6.12 ( 1 H, two dt, J 10, 6 Hz,=CHCHCH,), 7.8-8.5 (4 H, m, [CHJ,), and 8.8-9.1 (6 H,m, Me,), m/e 314 (Mf, 6%), 205 (M - PhS, loo), 163(PhSC,H,, 401, and 110 (PhSH, 70) (Found: M+, 314.1158.CloH,,S, requires M , 314.1161).3-Methoxy-2-methyl- l-phenylthiobut- l-ene (28) .-Di-phenyl(phenylthiomethy1)phosphine oxide (2 g, 6.2 mmol),and n-butyl-lithium (2.9 ml; 2 . 4 ~ in hexane), were stirreda t -78 "C, in dry THF (40 nil) for 0.2 h . The orange anionJ.C.S. Perkin Iwas quenched with 3-methoxybutan-%one 30 (27) (0.78 ml,6.8 mmol), and the mixture was allowed to warm to roomtemperature during 0.5 h. A thick white precipitateformed, which was dissolved with aqueous ammoniumchloride, and the product was extracted with chloroform(3 x 40 ml). The extract was dried (MgSO,) and evapor-ated t o give an oil. Column chromatography (CH,Cl,)gave the phenylthio-nzethoxyallyl compound (1.21 g, 95%)as a 1 : 1 mixture of geometric isomers, RF (CH,Cl,) 0.50,V,,~, (film) 1625 (C-C), 1585, and 1480 cm-l (PhS),T (CDC1,) 2.6-2.9 (5 H, m, Ph), 3.8 and 3.9 (1 H , two q,J 1 Hz, ratio 1 : 1 , CHECMe), 5.50, 6.24 ( 1 H, two q, J 6Hz, CHMe), 6.78 ( 3 H, s, MeO), 8.21 and 8.24 (3 H, two d,J 1 Hz, MeC=C), and 8.74 and 8.77 (3 H, two d, J 6 Hz,CH,CH), m/e 208 (M+, 45%), 193 (M - Me, 36), and 99(M - PhS, 100) (Found: M+, 208.0917. Cl,HI,OS re-quires M , 208.0921).Treatment of 3-Methoxy-2-methyl- l-phenylthiobut- l-enewith Benzenethio 1 .-The phenylthio-me t hoxyallyl compound(28) (112 mg) was heated under reflux in chloroform (30ml) with benzenethiol (0.1 ml) and toluene-p-sulphonic acid(35 mg) for 18 h. The solution was washed with aqueoussodium carbonate (20 ml), dried (MgSO,), and evaporated.The resulting oil after preparative t.1.c. (CH,Cl,) gave the1,3-bis(phenylthio)-olefin (29) (155 mg, 98%), identicalwith that prepared via 3-phenylthiobutan-2-one.[7/830 Received, 12th May, 1977

ISSN:1472-7781    

DOI:10.1039/P19770002263

出版商:RSC    

年代:1977

数据来源: RSC