Dichotomous ylide formation from an alkyl(benzyl)phosphonium salt leading to stereoselective alkene syntheses

摘要

1476 J.C.S. Perkin IDichotomous YIide Formation from an Alkyl( benzy1)phosphonium SaltLeading to Stereoselective Alkene SynthesesBy Brian G. James and Gerald Pattenden,' Departments of Chemistry, The University, Nottingham NG7 2RD,and University College, Cathays Park, Cardiff CF1 1 XLCondensation reactions between the tributyl-(4-methoxy-2,6-dimethylbenzyl)phosphonium salt (1 b) and severalaryl alkyl ketones, in the presence of methylsulphinylmethanide ion, are shown to lead to mixtures of stilbene andstyrene products, resulting from dichotomous ylide formation. By contrast, with p-anisaldehyde, the salt (1 b)produces solely the stilbene (1 0). and condensation between the tributyl-(4-methoxybenzyl)phosphonium salt(8) and 4'-methoxyacetophenone produces only the stilbene (9).The olefin-forming reactions between (1 b)and aryl alkyl ketones are completely stereoselective, leading to Z-stilbenes reg. (3) and euro;-styrenes e.g. (6).Explanations for the stereoselectivities are discussed.THE Wittig reaction is probably the most versatile olefinsynthesis known. Its advantages and convenience overother carbon-carbon bond forming reactions have beenstressed.l In the preceding paper we described theapplication of benzylic phosphonium ylide intermediatesin the syntheses of sterically crowded stilbenes. Duringthese studies we observed unprecedented limitations tothe ' normal ' Wittig synthesis which led us to examinecertain features of the reaction in greater detail.We have shown that condensation between the ylidefrom the salt (la) and 4'-methoxyacetophenone givesonly ca.2 of stilbenes (2) + (3) with trimethylanisole(4) as the major product (ca. 50). Use of elevatedtemperatures and an excess of carbonyl compound in-creases the yield of stilbene to ca. 25. An alternativeway of increasing the yield of stilbenes (2) + (3) ap-peared to be the application of the corresponding tri-butylphosphonium salt (lb). The ylide from this salt isexpected to be more nucleophilic, and the smaller n-butylgroups provide less steric hindrance in the transitionstates. Indeed, condensation between the salt (lb) and4'-methoxyacetophenone did give a greater yield of stil-bene product, but the course of the reaction was parti-cularly interesting.Chromatography separated three products, identifiedas the stilbene (3) (29), the hydrolysis product (4)(37), and the styrene (6) (14).Surprisingly theolefin-forming reactions leading to (3) and (6) were bothtotally stereoselective, giving the 2-stilbene and theE-styrene. Chromatography and spectral data did notdetect the presence of the corresponding isomeric olefins.The configuration assigned to the stilbene product fol-lowed from comparison of spectral data with those of theauthentic E-isomer (2) and also from the observation thatit produced the E-isomer (2) upon isomerisation in thepresence of iodine. The configuration assigned to thestyrene (6) also followed from comparison of spectral datawith those of the 2-isomer (7). Paradoxically, a Wittigcondensation between triphenylphosphonium butylideand 4'-methoxyacetophenone, under similar conditions,produced largely the 2-styrene (7) (2 : E ratio 9 : 1).The styrene (6) is produced as a result of intermediateformation of the ylide (5) from the benzyl salt (lb).Toour knowledge this is the first time that dichotomousylide formation has been observed from an alkyl(benzy1)-phosphonium salt. This observation clearly reflects thediminished acidity of the benzylic C-H bonds in (lb) overthose in other benzyl salts, presumably as a consequenceof the steric influence of the proximate ortho-methylgroups in (lb). A similar condensation between the salt(8), lacking ortho-methyl substitution, and 4'-methoxy-acetophenone produced the stilbene (9) uncontaminated( 1 1 a; R 2 P h ,b; R = n - BUM e 0 ck 'OMe(31(71with the styrene (6).With +-anisaldehyde, the tributylsalt (lb) gave only a mixture of 2- and E-isomers of thestilbene (10) (85); neither the styrene (11) nor thehydrolysis product (4) was detected in the crude reactionmixtures.Our studies suggested that only in those condensationsinvolving the salt (lb) and aryl ketones should we expectFor extensive bibliography since 1968 see S. Trippett,' Ylides and Related Compounds ' in ' OrganophosphorusChemistry,' vols. 1-6, Chem. Soc. Specialist Periodical Reports,1970-1975; see also ( a ) A. Maercker, Org. Reactions, 1965, 14,270;. ( b ) S. Trippett, Quart. Rev., 1963, 17, 406; (c) M. Schlosser,Topzcs Stereochem., 1970, 5, 11976 1477to observe products resulting from dichotomous ylideformation in (lb) ; this was confirmed in parallel studies.6 OMe( I b l ---+ @OMeMe0 Me0 '(101 (11)Condensations between (1 b) and 4'-methoxypropio-phenone and between (lb) and 4'-methoxy-2'-methyl-acetophenone both produced products (l2) + (13) and(14) + (15), respectively resulting from dichotomousylide formation. In both cases the hydrolysis product(4) was also obtained (3240).The configurationsassigned to compounds (12)-(15) , followed from in-spection and comparison of spectral data with those ofauthentic Z- and E-stilbenes and styrenes (see Experi-mental section).The stereospecificities of the reactions leading from(lb) to Z-stilbenes (3), (12), and (14) and E-styrenes(S), (13), and (15) are unprecedented.If we considerthat C-C bond formation between the ylides (16) and(17) and the aryl alkyl ketones is the first step in bothreactions, in one case (that leading to Z-stilbene) erythro-intermediate betaine formation viz. (lS) must be in-voked, whereas in the other (leading to E-styrene) ,threo-betaine formation viz. (19) has to occur (seeScheme 1) ; syn-elimination via the appropriate oxa-phosphetan intermediates formed from the betaines then/ (I21 OMe( l b l(13)(141 OMe (151leads to Z-stilbene and E-styrene. Under othenviseidentical conditions however, triphenylphosphoniumbutylide reacts with the same aryl alkyl ketones produc-ing predominantly the corresponding Z-styrenes (7) etc.;t In these reactions an E-stilbene could have resulted fromstereomutation of a pre-formed Z-isomer during reaction (seeExperimental conditions, preceding paper).see Experimental section. In addition , the triphenyl-phosphonium salt (la) either produces E-stilbene vix.(2) t or does not react at all with the aryl ketones. Inview of these comparative data it seems probable that themechanisms which operate in these reactions are differentfrom those in the reactions leading from the salt (lb) tocompounds (3), (6), and (12)-(15).An alternative explanation for the stereospecific re-actions leading to compounds (3), (6) , and (12)-( 15) canbe formulated, based on initial co-ordination of carbonyloxygen to the phosphorus of the ylide (lb), leading to anoxyphosphorane intermediate (Scheme 2) (for discussionof this approach see ref.2). Formation of this type ofintermediate is plausible in the special case of (lb) andaryl alkyl ketones, because of the mutual inaccessibilityof the carbon centres in the two reactants. Models sug-gest that this sequence could lead to an oxyphosphorane6 u BuA r CH, P- CH, Prbsol; /d.6 u Bu // / /A r k H -P-C H2Pr *bsol;bsol; BU Bubsol; /ArCH2-P-CHPr + -(161 (17;iA r ' Me Me Ar'C' 0 - / bsol;Ar H1C' 0 -/ bsol;Pr H 19 1 t h i e o( 3 ) E I C . ( 6 I e!c.SCHEME 1(20) which might equilibrate with a second oxyphosphor-ane (22) by intramolecular H exchange. With both aryl(Ar) and propyl (Pr) groups anti see (21) and Arorientated in the least sterically crowded section of theequatorial plane, a rotational movement to the left aboutthe C-0 bond would lead to the erytkro-intermediate (23),whereas a rotational movement to the right would lead tothe ' threo '-intermediate (24) ; collapse of these inter-mediates by syn-elimination would then give rise toZ-stilbene and E-styrene, respectively.+EXPERIMENTALFor general experimental details see ref.3.Tributyl-( 4-methoxy-2,6-dimethylbenzyl)phosp~ honiumBromide (lb) .-A solution of tributylphosphine (18 g ) in drybenzene (100 ml) was added dropwise to a solution of2 W. P. Schneider, Chenz. Comm., 1969, 786; see also E.Vedejs and K. A. J. Snoble, J . Amer. Chem. Soc., 1973, 95, 6778.3 B. G. James and G.Pattenden. J.C.S. Perkin I , 1974, 11951478 J.C.S. Perkin I4-methoxy-2,6-dimethylbenzyl bromide from 4-methoxy-2,6-dimethylbenzyl alcohol (16.6 g) in dry benzene (50 ml),and the mixture was then boiled under reflux for 2 h. Thebenzene was removed i n vacuo, and the residual glass wasthen triturated with dry ether to give the salt (34.2 g, go),as a white powder, m.p. 124", vmX. (Nujol) 1610, 1585,1510, 1250, 915, 840, and 735 cm-l, T 3.4 (2 H), 5.97 (d, J15 Hz, ArCH,*P+), 6.24 (OCH,), 7.54br (s, 3 x CH,*CH,),7.6 (2 x XHCH,), 8.55br (s, 3 x CH,*CH,.CH,CH,), and9.1 (t, J 7 Hz, CH,*CH,) (Found: C, 61.1; H, 9.7. C,,H4,-BrOP requires C, 61.3; H, 9.5).Reactions between Tg.ibutyl- (4-methoxy-2,6-dimethyZbenzyZ) -phosphoniuvn Bromide and AryZ Ketones.-The reactionscm-l, T 3.08 (2 H, d, J 9 Hz), 3.40 (2 H, d, J 9 Hz), 3.53(2 H), 3.72 (CXH), 6.32 (OCH,), 6.35 (OCH,), 7.79 (XCH,),and 7.98 (2 x XMe) (Found: C, 80.65; H, 7.9; nz/e 282.C,,H,,O, requires C, 80.8; H, 7.85 ; .!W, 282).The stil-bene was isomerised to the corresponding E-isomer withiodine in acetic acid (see preceding paper).(B) With 4'-methoxypropiophenone. Chromatographygave : (i) (E)-3-(4-methoxyphenyZ)hept-3-ene (13) (0.1 g, 5)(eluted first), hx 252 nm; vmX. (film) 1610, 1575, 15101250, 1035, 830, and 800 cm-l; T 2.75 ( 2 H, d, J 9 Hz),3.22 (2 H, d, J 9 Hz), 4.45 (t, J 7 Hz, XHCH,), 6.23 (OMe),7.55 (9, J 7 Hz, :C*CH,CH,), 7.85 (q, J ca. 7 Hz, :CHCH,CH,), ca. 8.6 (m, CH,CH,.CH,), and 9.06 (t, 2 x CH,CH,)A r C H - p u 3I - Ar', +c - 0Ar', 7 c=oMe' Me'- A r zP.Me IAr''MeIB UIBu1201 (21 I ( 2 2 ) J(231H /-I13 I etc.'Pr1241(61 etc.SCHEME 2were carried out according t o the general procedure de-scribed in the preceding paper.Products of reactions wereseparated by chromatography in benzene on silica gel.(A) With 4'-methoxyacetophenone. Chromatography gave :(i) (E)-2-(4-methoxyPhenyZ)hex-Z-ene (6) (0.28 g, 14) (elutedfirst), Lx 270 nm, vmX. (film) 1 610, 1575, 1510, 1250,1030, and 830 cm-l, T 2.7 (2 H, d, J 9 Hz), 3.2 (2 H, d, J 9Hz), 4.32 (t, J 7 Hz, CHXMe), 6.28 (OMe), 7.95 (9, J 7 Hz,CH,*CH,CH), 8.03 (XMe), 8.55 (sextet, J 7 Hz, CH,*CH,*CH,), and 9.06 (t, J 7 Hz, CH,*CH,) (Found: m/e, 190.1358,C,,H,,O requires M , 190.1358) ; (ii) 3,4,5-trimethylanisole(4) (0.58 g , 37) (eluted second) identical with an authenticsample ; and (iii) (2)-4,4'-dimethoxy-2, 6,a'-tr~methylstiZbene(3) (0.85 g, 29) (eluted third), which crystallised fromethanol as needles, m.p.72", LX. (EtOH) 268 nm (8 700);v,, (Nujol) 1608, 1575, 1515, 1250, 860, 825, and 805(Found : m/e, 204.1514. C14H200 requires M 204.1514) ;(ii) 3,4,5-trimethylanisole (0.59 g, 40) (eluted second),identical with an authentic sample ; and (iii) (Z)-a'-ethyZ-4,4'-dimethoxy-2,6-dimethyZstiZbene ( 12) (0.9 g, 30) (elutedthird), which crystallised from aqueous ethanol as needles,m.p. 68", kx. (EtOH) 270 nm (10 950) ; vmx. (Nujol) 1 603,1 510, 1 250, 1 150, 850, and 835 cm-l, ?: 3.1 (2 H, d, J 9 Hz),3.5 ( 2 H, d, J 9 Hz), 3.55 (2 H), 3.75 (olefinic XH), 6.3( 2 x OCH,), 7.42 (9, J 8 Hz, CH,*CH,), 7.97 (2 x arylX-CH,), and 8.9 (t, J 8 Hz, CH,-CH,) (Found: C, 81.2; H,8.2; m/e, 296.C,,H,,O, requires C, 81.0; H, 8.2; M ,296). The stilbene was isomerised t o the correspondingE-isomer with iodine in acetic acid (see preceding paper).(C) With 4'-methoxy-2'-methyZacetoplzenone. Chromato-graphy gave : (i) (E)-2-(4-methoxy-2-methyZfihenyZ)hex-2-ene(15) (0.07 g, 3.5) (eluted first), nD2, 1.5160; hx (EtOH1976 1479230 and 275 nm, vmx. (film) 1 605, 1570, 1500, 1235, 860,840, and 800 cm-l; z 3.07 (d, J 9 Hz, aryl XH), 3.34 (arylXH), 3.48 (d, J 9 Hz, aryl XH), 4.76 (t, J 8 Hz, CXH), 6.28(OCH,), 7.78 (aryl :C*CH,), 7.88 (q, J 8 Hz, C:CH*CH,*CH,),8.13 (olefinic CH,), 8.56 (sextet, J 8 Hz, CH,*CH,*CH,), and9.05 (t, J 8 Hz, CH,CH,) (Found: mJe, 204.1514.C14H2,0requires M , 204.1514) ; (ii) 3,4,5-trimethylanisole (0.48 g,32 yo) (eluted second), identical with an authentic sample ;and (iii) (2) -4,4'-dimethoxy-2,2', 6, cc'-tetl.amethyZstiZbene ( 14)(0.3 g, lo), an oil, kx. 231 and 280 nm; vmx. (film) 1 610,1575, 1500, 1260, 1 190, 1 160, and 835 cm-l; T 3.23 (d,J 9 Hz, aryl XH), 3.4-3.7 (m, 4 x aryl :CH plus 1 x ole-fink XH), 6.4 (2 x OCH,), 7.85 (olefinic :C.CH,), and 7.96(3 x aryl :CCH,), r n / e 296 (C20H2402). The stilbene wasisomerised to the E-isomer with iodine in acetic acid (seepreceding paper).(D) Reaction with P-anisaldehyde, followed by chrom-atography on silica gel benzene-ethyl acetate (97 : 3) gavea 1 : 9 mixture (85) of Z- and E-isomers of 4,4-dimethoxy-2,6-dimethylstilbene (10).Crystallisation gave the E-iso-mer, m.p. 82-83', identical with an authentic sample.(2)-2-(4-MethoxyphenyZ)hex-2-ene (7) .-By the generalprocedure, butyltriphenylphosphonium bromide and 4'-methoxyacetophenone produced a 9 : 1 mixture of Z- andE-isomers of the alkene. Chromatography in benzene onsilica gel gave: (i) the (2)-alkene (eluted first) (70y0), T 2.93(2 H, d, J 9 Hz), 3.2 (2 H, d, J 9 Hz), 4.6 (t, J 7 Hz, :CH*CH,), 6.28 (OMe), 8.05 (9, J 7 Hz, :CH.CH,*CH,), 8.02(ICMe), 8.62 (sextet, J 7 Hz, CH,-CH,CH,), and 9.18 (t, J7 Hz, CH,*CH,) (Found: m/e, 190.1358. C13H1,0 requiresM , 190.1358); and (ii) the E-alkene (eluted second) (lo),identical with an authentic sample,(2)-3-(4-MethoxyphenyZ)hept-3-ene.-By the general pro-cedure, butyltriphenylphosphonium bromide and 4'-meth-oxypropiophenone produced a 9 : 1 mixture of Z- and E-iso-mers of the alkene.Chromatography in benzene on silicagel gave: (i) the (2)-aZkene (eluted first) (65y0), z 2.96 (2 H,d, J 9 Hz), 3.20 (2 H, d, J 9 Hz), 4.63 (t, J 7 Hz, :CH*CH,),6.26 (OMe), 7.69 (9, J 7 Hz, :C.CH,CH,), 8.09 (q, J 7 Hz,:CH*CH,*CH,), 8.69 (sextet, J 7 Hz, CH,*CH,CH,), 9.06 (t,J 7 Hz, :C*CH,*CH,), and 9.18 (t, J 7 Hz, CH,CH3) (Found:m/e, 204.1514. C14H2,O requires M, 204.1514); and (ii) the(E)-alkene (eluted second) (6y0), identical with an authenticsample.Tributyl-(4-methoxybenzyZ)fihosphonium Bromide (8) .-The saZt, prepared from p-anisyl alcohol via the correspond-ing bromide in the usual manner, had m.p. 62-63", vmX.(Nujol) 1 605, 1 580, and 1 510 cm-l, T 2.14 (2 H, d, J 9 Hz),2.58 (2 H, d, J 9 Hz), 5.59 (d, J 14 Hz, ArCH,-P+), 6.2(OMe), 7.4-7.7 (m, 3 x P+*CH,), 8.4-8.6 (12 H, m), and9.05 (t, J 7 Hz, 3 x CH,*CH,) (Found: C, 59.8; H, 10.1.C,,H,,BrOP requires C, 59.6; H, 8.9).(E)-4,4'-Dimethoxy-a-methyZstiZbene (9) .-By the generalprocedure (see preceding paper), tributyl-(4-methoxybenz-y1)phosphonium bromide and acetophenone gave the stil-bene (60y0), m.p. 122-123" (from glacial acetic acid) (lit.,4124"), z 2.55 (2 H, d, J 8 Hz), 2.71 (2 H, d, J 8 Hz), 3.11(4 H, d, J 8 Hz), 3.3 (:CH), 6.2 (OMe), and 7.75 (:CRIIe), rn/e254.We thank the British Petroleum Company Ltd. for aresearch scholarship (to B. G. J.).5/2379 Received, 8th December, 197514 R. L. Huang, J . Chem. SOC., 1954, 2539