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Date: 16 May 1989
Length: 274 pages
87503039-87503312
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Skladanowski, L.M.
Viso, M.E.
Vollmuth, T.A.
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Page 161: mju35a00
388 Faamcett and Gibson : Tke Lnfluence of Pressure on tlle cffect of'f presswn:on organic reactions iii gouer.d, and we have tliereforc undertaken,a survey of such..pressurc cffbcts.s in the light of the possible ihfluencesdiscussed..above. For instance, a rcaetionn such: as the Dielsreaction, which occurs between substances of high reactivity at atmospheric pressuree in the absence of'~ catalysts; m'aghtt occurr under high pressure between similarr substances of lower reactivity. Agaih,, a reaction which proceeds readily at,atmospheriic pressurein: the presence of a catalyst might proceed rradIly without that catalyst underr pressure.. Finally„ a reaction proceeding, at atmosphericc pressurein the absence of catalysts might proceed faster.under pressure.. The.choice of..reactionswassomewliat limited, for it was desired~, in the first instance, to study reactions in the absence of solvents„ whilst it was.considered d'esirablp that part, at least, of'f thereaotion mixture should.be liquidi at the highest pressures.tobe used.. It had therefore to~ be bornein mind that a pressure:of 3000 atm. increases the melting.points of most substances by 40--80°.. It was.also necessarythaty the reagents should not react with the mercury used totransmit,the pressure. The survey nowcovers some 50reactions of'different.types,which have.been: studied under.pressuresupt'o3000.atm.and.atltemperaturesupto180°. Anoutl!ineof the results obtainedisgiven,below. - ~.. ResuZLs:-Fiom a study of thee reactions between maleic anhydride and at~omatic compoundi;:it was found tlhaat.reactionsof this type, which do not proceed at't atmospheric pressure (in the absence of'catalysts) ~ ., do not proceed at a pressure of 3000 atm.. and the same conditionss of temperature: e.g., althoughh malbi:c anhydtide and anthracene condense readilyat.200°'and slowly in toluene solution at.40°'at atmospheric:pressure„no.reaction occurs at either atmospheric pressure or, 3000 atm. betweenn malleic anhydride and the less reactive naphthalene„toluene;, or benzeneat'e temperatures up to.180'., The study was then extended to reactions between phthalic.c anhydride and aromatic hydrocarbons, which aree known to occur only in the presence of aliumini= chloride. It was again found that therewas no ~reaction under pressure:in the absence: of catalysts or in the presence of milder catall'ysts:. In view of these negative resultss some.reactions~.which normally proceed in. the presence of'f milder catalysts were next tried, and..it was found'.thatthe reactions between aromatic amines and benzaldehyde,, which are catalysedl by acids„ weree markedly influenced by pressure; e.g., the reaction between d'imethylaniline and benzaldehyde. (with noo great precautions too remove the last tmcesof benzoicc acfd) proceeded slowly at atmospheric pressure at', 150°„ buk theyield'e inn the same time was increased about 8-fold at 3000 atm. at the same temperature;, and.that the.pressure effect pecsisted,in the presence of 1°fo of benzoio acid. On the other hand,, the less reactive aromatic ketones did not react with dimetlhylanilineat I80° either at atmospheric pressure.or at 3000 atm..in the absence of added catalysts. Owing, to the great difficulty of ensuring the absencee of acidss in reactions involving benzaldehyde, and Ibecauseofthe failureof ketones.to.s react:with aromatic:amines, a similar type of acid-catalysed reaction, viz.,, thee acetal reaction, was now sthdied. Itt was found that acetaldehyde and ethyl.alcohol (both freed from.acid~substanees) reacted slowlyat atmospheric pressure at 60° but.gave a 9-fold yieldd in the same time at 3000 atm:. at the same temperature: Attempts to prepare acetal fnom~ the lesss reactivee ethyl ether by the reaction C81',-eHO,-I-EtyO ) CH,.CH(OLt)s,, which. is not known to occur under any conditioas at atmospheric pressure„wcre unsuccessful at 3000 atm. Inn viewof.w the positive pressure effects found with acid-catalysed reactions,, some examples of base.catalysed.reactions weree tried, but the.effects were less marked. Acetalde- hyde and ethyl.l malonatee or acetoacetate showedi no, detectable reaetionn either at.t atmo- spheric.pressure or at 3000'atm, in.the:absence of'~a catalyst, and similarly the.tautomeric change: of o-xylylene dicyanideintoiminocyanohydrindene,.which is.only known to.occur im . thepresence of sodium ethoxide,, could nott be made to proceed under pressure without this catalyst. Benzaldehydee andchloroform, whichh react very slowly at atmospheric pressure, showed a small increase in.n reaction mteat 3000 atm. The:investigatione was nowextended.to reactions whichh.are known.to proceed at atmo- spheri salt f pressi Cetyl Attem or me to no spheri a'tion give cr quate:. Zrietll but re the h servea the ac ezaml previc A:, i procec iatere: exerci.: wliirhh the pr whilst. Th substa found, from t In lheen e cdrang pated, tempe Co resulte (li) Al at Th mtaly slowly were f. of the. outlin tonsc. An nearly inthe: (2) Tlr di. 17hi' The on, no det possibl ~
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i 1250 Scheme: I G G U~- S~toll+ R'xR2 <R 1.1+)-ll 24 R' •CeMk. FZ..CMa. S 2b~.RP•C2Hk.N CHS. !: Am:.Chem. Soc. 1987, 109, 1250-1252 R2 O R11 m~ g.1 tail (S5..4R1:-4l~I,R, CdHy,fl?''•CH'e. (Sy..4S t-4b.R:' • C2N5. R~'• CHS,. R~a R111H1-r-S-tot [R4-1-l.aa R' • CeHS. R2• iS)-(-r-e e: R' • a2HS. R? • 8elene R CHa a CeHSmT--r - CsMSUUT--f - . S-CeHy S-CeHy (4A):-7 .. (4A)-g CHJ CaMen+~ - H imC-CO M C R'1H (,B)-(`)-ea.R'•CSNS, R2 CHS Oi.R'•C2HS. RZ-CMg S S 2 CH2-COpH ' ,-12 (W1-11 (R):-(-) phenylcyclohumnone (6.) ([ap°o.-9.6° (c 3:0; EtOH)): in 86% yield (Scheme 1)1 The absolute canBlgurationn and the enantiomeric excess of the product'.6a were determined ae (R)-(-)'-6aand 94.096.ee by, chemical correlation of (:-)-6r with (R):(-)-2-meahyl-2-phenyl- succinic acid (12)j of known configoration' asdollows. Sulfeny- lation of the ketone (-);5a obainett above with diphenyl disulfide followed: by.sodium borohydride reduction of 7 produced an~a- phenylthio aloohol.8. Alcohol 8 upon treatment with lead tetn- aacetate.in toluene-ace6c acid (4:1) at:0 °C.for 8'.h und6rwent an oxidative'.cleavages m:give a thioacetal acetate 9'., Hydrolysis of thisacetate 9 with potassium hydroxide in, methanol at roam tempemturegave a.hemikcetal.lOL Oxidation*f thishemiacetals g0iwitk chromic acid in'aqueous sulfuric acid-acamne.at..0 °CC produxd.2-melhyl-2-phenylkua,tinic anhydride (11)1, which uponn tiydiolysii with potassium hydroxide inrefluaing methanol gave (i!E)F(-)-12 ([a[30n-18.8° (c 3.5,.EtOH), 94.0% ee)7 (Scheme 1I), The reaction sequencesatarting with ethyl methyl.ketone ('Sb) were successfudlyexeculed in, the: same way:. Addition of the.a-carbanion of (lts):-(+)-h (100% ee)f to 2b, gave (Sa)-3b.in.72%.yield (ttw.diastcreomen of 3b (ratio 3:2) weme unseparable). Thethermal.rearrangement of (Ss)-3b thus ob• taihediwas arried'.out by'treatment with p-toluenesulfonic acid in neHunibg benzene foc3.5 k'm furnisha.cyclobutelie derivative (SS)-46 in 65% yield. Reduction. of the sul(loxide (SS)-46 withh acctyl chloride followed by hyd'rolysis of the enol thioether(-)-5b (7) AbhayeR R.du:; Dabard, RL rnroFed`on. t975;.31„21',11. (8) Trarl, B. M:':gliroi, K. J. Am. Cliem. Sac. 1975; 97; 6911. 000T7863187/11509-1250801.50J0 Sch'enx.Ill ~ ~ Hr. O 0 0 S_~lol - ,J. ~tol + R2 uu~+ $~ lol 156 16b 14 . prod'ucedi(S)-(r)-2-ethyl'r2-methylcyclobutanone (6b)1 The abr solute configuration and't8e enantiomeric excess of.the product 6b were determined as (S).(-)fib and 73.3%ee by transformation of 6b into 4-mcthyG4-hexanolactone.(13) of known configumtion)A Baeyer-Yilliger oxid'ation.of'(-)-6b.(H4Os NaOH.in aqueous methanol) followed byy lactonization by heating in refluxing benaenu.with~acatalytieamount of p-tolhanesullbnic'acid led to(S)-(-)-13 ([a]va,- 6.3°(e 10, CHCIa)6 73.396 ee)! On the basis of the above experimental.eesults, the asymmetric inductions inthese'.thermal l,2-rearrangements.of'..3a,b to 4a,b were determined too give 94.0% and 73.3% optical, yields, re- spectively. Fromehese slereachemicall results, themechani4lic pathway for this asymmetric ind4ction'would berepresented.as follbws. In the acid-catalyzed thenmolysis, the carbonium ion 14.would bee formed initua0y, The 1~2-migration of acarbon-carbon, bond of the eyc.lopropanaringwouldioavr via a transition smte_ 15, and a newasymmetry+ wou8l be.induerd at lhisstage.. The degree of asymmetric induction, would depend on the difference between, thethermodynamilcal smbility.of 15a and 151i;.thatis,.on the differenae of the steric interference betweeh R' orRx and ttie.lone pair or the oxygen.atom.of the chiral sufloxide (Scheme.IlI)i. The eaay access.to the.staning chiral sulfaxide and the high degree of asymmetric induction in this thermal rearrangement represent a pmentially great advanmgefor the construction af' asymmetric quaternarycarbons. Furthermore, this method provides a facile entry to chiral cyclobumne derivatives, which~h have usually been hardtoaccrss. (9) Mayer, H.;SchudeL PL; Ruegg, R.;,Isler, a Ne1a..Ch7m. Aam1961- 46, 963. Biasynthesis.of the Mbdifsed Peptide'.Antibioti'e'. Nosiheptide: in Streptomytes a¢luasns' David R. Houch, LiiChun Chen, Paul J':. Keller, John MI. Bealk, and.Heihz Gl Flass' Deparsmentof Chemistry;.The Ohio: State bfniuersiry. Columhus.Ohio 4321%0. Receiued' A ugust 4: 1986 Nosiheptide (1)','u' a metabolite of Streptomyces actrrosus, isa namlber of a broader class of highly. modified, pulfur-rich pcptide antibiotics, which alao includes'.thioslrepton,3microeoccin,c the thiopept'snss and several other compoundb.Compound I iahibitsprotein synthesis inGram-positive bacteria by binding to the.50S. ribusonalsubunitsilis used asan animal-f¢ed additive to inaeasee weight gains.2Nosiheptid'e cruntainsseveral structural ell-ments: (Ip PaacarQ C.; Duernix, A.; Lunel, J'.; hange, T. J: Am: Chem. Soe: 1977,.99„64181and refereeceutherain. (2) Endo, T;Vonehar., HI.J. Amlbfot.1973, 31, 623. (3) Anderson, B.; Crowfeut-Hudgtln:DL; Vuuramiua, M..A. Narurc (Landon)I 1970;.725, 233. (4) waRier, l.; Olaker, A.: Vakate: L.: Ranatial', R4,W kaet, 6. J: Chem.. Saa; Chaw: Commun..1977; 706. (¢) R6nrenr, OL D~:; A18errSchenenbere,. G. Ji Amf6ior. I8V3, 36:/14. (6) Candaffd E.;'Qhampon, J. J: Gea, MrcroNor..198t. 126, 181 (7) Bcozaet, Pq Cartier, M:;. Flar<nt, J.; Goaard, C.;,Jang.6.; I:unel, J.;,, Maney, D.; Puw4 C:;.Renaut. J.;:'Parridee, P.;: TheRkux, JL. TiWer, R:;. Duboq gL: Ninee. L. SxpeNentW'1fBg,.36. 414:.. 0 1987 American Chemical Society
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LSoaxas u.. M . Gsasraa Jiraa~TatauchoorkL'urt kcmMaOee diebenach- er Butanolide I 0-1 g, -rn nur Methyliisrungs- lgmppe). schonn wieder sen aich sowolil gegen- : on 4ber zwei,Stunden xlukte bTa und bl.b COCH wfjHe. Rcaktimmn von Butnnolldcn.mitDimethyl- und D(athyl-aluminiumclrtorid 281 Weise an. ])er Antci], mr 3'b mrd 4 b.nimmtabernicht.linear zu,.diegro6te Anderunglicgt bci.n =1,2'bis.1„11. Variution.dca Molvorh-altniases ((ir n= 1,2L) zwi3chen 1:1,2 wid 1:4,5 boweist Sclcktivitii.tl der Spnltungeroaktion.., , Wenn mehrC_H6A1CIz.zur. VcrlGgungateht, reagiert descs. bevouzugt. Diese Wir- kung entspricht cinem.lrulreren Chlorgohalt fur Srersuche mit konst'antemyr aber niede- relnMolWerhaltnie und fulirt demnach zu ateigendem Anteil angesattigter Siiure 6 1. Erst bei Molverhaltnissen von 1:3und h8her liegt im Bsaktionagemiseh genGgend. CqH6A1Cls fiir die. Bildung gr8lierer Anteilee an gesittigterSaure 6 b vor. (Tab.6):. Die bier erhaltenenErgebnissewerden. verstiindGcher,, wenn die amButanolid 1 C ermit- telten Aktivierungsenergien verglichenn werden. Danach 16uftt die Spaltungereaktionn mit. (CaHs)$A1Cllbei 23'3 keal/Mol (oxperimenteller Teil)1 mit CQH6ALC1=, abernuebei. ]'3 kcal/Mol[1] ab. Tabolle6' UmsctzungdasButanolidslbimit(CaHr)al75AIClr.es+Abhiingigkeit vmm Molverlialtnis Molverhultnis Temp. Aue6. Susammensetzungd.8fiuren(a/o) (°C) ~ (%)'., geeitt: (Cb) ungeditt. (8b + 4b). 1i:1,2' 42 16 23 77 1:1,5 24 89 30 70 1:2,5' 18-21 87 31 69 1:3 17-21 87 72 28 1:4 1G-18 87 g1 19 1:4,5 14-16 90 86 16 lem Butanolid . I b zu a 8 b and 4 b. Ds.bei ig des Sauregenuisches ,AIQ, ab;, wobei dfese ensetzung desSaure- ler Zusammensetzung 2,04end 0,75 wiefn imender Lewissnure- 1 b) . iu iiborsiclrtlic)ier ]r-Gemischen wagd. Siuren. (%) uages5tt: (a b.-1- 19k), 6 29 . 54 80, 76 DieGrenze der Spaltbarkeit des Butanolida.zu Carbonslure ((¢zH~),Alalkyliertl in. Gnmxxa.D-analeger Beaktion zu Diolen) liegt zwischen n.=-0;5 und 0,2.. (C2Hs)zsAlClo,e spaltet dasBvtanolid I b bei auareichendem Molverhsltnis nar nooh zu 37%% zu. Sauren,. (C=Hs).s¢ICld.q gibt praktiaeh keineSauren mehr;;eatrittaus- ' schlieBlich.Alkylierung des Butanolids zu Diolen. ein [4]. Fiur dio unter Leitungvon Herrn Dn Fwex suegefuhrten EI'omentarsnalysen und gaachromato- graphischen~Untersuclmngan sowie die von Henn Dr. Ej Gai)xnaersNn aulgenommenenr$-NMR- Spektren mochten.air ganz besonders danken. FrnrnMOnusu dankon wir fia dio exakte Durchfuhnmg von prupamtiven Arbeiten. Beschreibung der Ycrsuche DieAuegangsaubatanv.en wurdmr nach Ileknnnten. Vorochrifton dargeatellt. Die Butanolide l ur-g stellten wicnuwh.[5], dhs 4-Athyl'.hezcn-(2)-alid-(4,1) i9'a naeh [6]pnd 3, 3-Diathylphthalid'3h ]mc[, .[7]Idm'. Die Dan+tclllmg,von 4-fficthyl-[5:-Dr]-Imxanolid-(41.1) li orfolgto.durch Umeet-zmlg vmr l.iiviJii,Kiurunmthylextun mitl [1-D}l-Athylmsgnoeiurnbromid untorden.. Badingungen von [`]: Von, den: nlu mioiunwrgmiiuclron Vcrbindlmgcn wurdoo dae . (CyH}):Al laus dem VEB Chemikche N'erke.Bnmu;. Scbkopmq bezae n, dirs (CrHy)rA1CI dlacluMi+chen von (C.Hy)yAl mit'(C.Hs)~S11yCh odor AICh und anxeWiuBendcm. Roinigeo,dircclvDcwtillation nach [8] crlialten, . and due (CHa)i;A1Cl tmd.(CH,)Y41'yCh 1uwIi [p9] dargextollt. Die 1H-M1lfllt-Spoktrun wurdon mit vinem Vorian.Spoktro- g'RBhonn A GGA inn fetncblerkohlonstaft aleMenngumittcl. unter Zueatz von Totrumethyl9ilan. au[genemmon..
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u.. cAItCCU, C.. ql':CWNCN J. JyV:uUl::, ;rwoims des alcnnls secondaires dc. 1loucen (5). lo I- jc,a.-c1_alofrjrptyl'T.SVctnpont5llaf,...dpr(•s li.'adentut par un excixd'anhydrikle_ pltenylbutyriqur. Journit unr. Iraetion actdc non aontUincelevogyre : donc. I'encombre- ntent dhos cat alcool est. • aAroito-s, de.surteqn'il'.pns;i•do . laeonliguralion absolue indiqpce sur In ligurc 41. II s'ngil( du e.yctopen~lyl-2(4), cyclopcatanolbl(et):. ll'aprns la m6mo methodc„ to (',t)i trnascycli+.pentyl-1 ruulo{tenLanol' a Agalemcnt la conIlj;urvainn S pour I'tdII; c'/~st Ieex'rlopentyii-9(R) ryclbpentuml-11(.<) 7(•),. a cnnuliliunquc Ioo ditlonhlvutcuL drs :Jrool4 cisrt traus ait. dtcmen6"a son termc, a!rsl-h-0Vre jasqu'ir ohlrn- tion d6composest optiqucment pnrs, on pout supposer quelafaiblefnaction d:'itlcool''trmts (4.';n)I qui snuillc tc (+) ci.rcyclapcntvl2(S) cyclupenl:umid(S) 4' tstl Ic (+) transs cyclopeniyl-_(It) cyolopentanol-1'(S) 7('•). Par oxydati!on, lo (-1-) ctscyclopentfl-2 eycfnpmd:urnl magpusipnt pnm• (Inuu r ho y-ntdl'byll p-ulhyl hu.Lyrolac- _lone 9. 7 r•tilie, p:v I:ICidn pulypLlospltoriquc;4 celle•ei subit: . unrcnrnulR'•mrnt qrti, donnu la dimcthyl-2,3'3 rycln• penl0ne-?~ onu.{ L0l 1.'hydlrngi•nntiant catnlyliiptn dc 1l1', clrprdsr•nrc do Pd)'C, finvnitt un utclaugc' dc dcusx c6toncc salur6es, nettemnnlt si~p:u,irs. par clrrumaingraphin g;iaeust•: Qwmd orclLptillhrr rn mrLmt;n par 1'aa snudc onsulut'ion alcnolilpuo, on cnnaalr ~pm Ihpruduil inil.iall-ment Ic plu.s ntundanl so I:rum.vflnnn•.prr=,1u, numplV'qruluuL eni.l'anlm : ii 1'e,lui- lihrr,. In nuHmyo• rn cunticul'JG %. Comnm, dnns.lflivd.re- ghnations raLdytiiptr, I, s dhttz ulomess d'hydrugene nrrivonl parLa mr'mc Gtr,e de la molCculc„ Ia n/•Innc la plus :tliund:ml.• iuil.ialhurrnl r.al'lr•i:x prohoLlemwrd. In i(•tnnc cis; ,lur .'isum,riso (') p;rrhnnliiatiun an: o;1'uno trtms: dmrnc Ih: cLlone lEvogyro 5ct la. (+)) tranr cyl,loprnt.y.1-"_ oy,-cn-ot,-eNl,-co,- ~. e cyelbpentanol 7 donne Iacclone dextrogyrr.8,. Coxydalimt l' l l i ' a eoo da cts(-I-) qu conlicnt 4% d alcool trmrs (+1 CM: conduit done h 8: ^o de cc't'one racAmiquoef. 9" 'o dn ' celone IAvogyre. Geci nuns permet d'interpr6ter IaidiQ6rencu.dtspournirs a ,`I" rotatoirxs oLservNs pour lesdeux.c6tones anl-opodes. \ous 0 0. avons vuu quo I'antipode 16vogyreo a une purrtn~ optique Ia de9^_ %, c0 on montre par un raisonnement an:dngue, un, .CH, ~ que l'antipode.dexlrogyre a.une puretc nptiquedb 85 0~' . RBirlivemenk on. trouve qurv los dk•ux~x anlipnde•c nnt d,s pauvoin rol'atoires do-9'l^ et. + 8G^ respr.otr.+ m, nt, 0 oH ce qui correspond pour'la cetone opliquemenl pure ;r un Ir Lt pouvoirrolatorre de 100- ern+ironn en valrur ahsolm•. p. - Crcloperrtanols et cyclopentanones: disubstitufs. - La dkubslitntion do In cyclopenlnnonu (si 1'un cxrlut Ies, disulislitulSonsgeminees) pcut, conduil•.r.:mx. qurlro arrangements ci-dessous, pouvant'.cuxanPnns idrr Ic sl(•gc d'mtr isumcriccis.erans:. 1'arnti cesdlivenes pussihilliles;, seuli, aiilu dirrilo ru sirie optiquotuentactike, u.nolre connaissancr, la dinti•- Ihyl73,4evclopentanone trans; prefutrec par CvnvIeoM par (I'egradation del'acide gataretlquo (6). \ Y\ 0 0 0 0 Nous dt.criirons la pruparationdo trois c6lum s curn.- pondanl auxtroisdes premiers types ci-dessus, r n I rr r1- sant les conf(;urationsabsolues quo nons avnns pu f•nr altribuor: A) D6nAtliyf-P,41 cycloprntnnonc. La dim@lhvl?^_,3 cyminpentanone racemirlur aiac pr:eparec parunc suite:de reactlons.dcja.dcorifes (,9, 8, 9) Irl'•rul:ete de.nycloliexylu 8 so conalense avoc Ib' brnm,vr d"ulhvl- 1•I' Le'e rendtunentt ol'liqnr ,hr diduuLlemrnl r.c{ dr.. t11,5. paurl'iwmereair ct.de':•3 ^." paur I'isn,nirr rrnns. Ccn'wull:;l rstremanluablr rn ce.qu'tl audique un nrus rnavnhremrnt dr I'prdrox)ie dunsJ•isn,n@re rcm,x, qui nnprnl;s'spliqm•r ,pwpar anedrfurmnliim dm ryclr: I;i•Imlc d4ndr-s cyrlnprnl:nn•1. y.subxlilhi•s'. uyliqumnent nclifs xv:eait nice.5uire pnnr Ilri.riw•e vr pemarqpnns rtlm 1:t n•Ide9IC RhsTrrEn (.'J ,sf r(•ri0im pour n daMoublcmeuP: Ieu.:u,liPUdrs. ds derz: phbdidr< :rriAr:„ ri.+ el.trnn., qut ihrmlrnll ar.rr Ir rnJmo alrt,Lndr IL, ,iinlwuinr) rldans lesnri•mes solrm,ls, Irs srls IcG.utoiaxsnhdd,•., sunl ..re- Pqumrnt relt.r.: les atc.oals corerspnndanl:virel'.rrnnr, md la nime cauGguralinn abnnlLc(S) pnnr Phydroxyic. It'•duil,+ p:rrhv ndinnl. .•t I'abvul~ la trmtx dimGllhyl-P',3 uy,rlupcnlunuuo 10 dumtr In dirneOrvl-2',a cyclnprnl:utol 12 qm,.:tpres.dislillal.iun. ,-sl pur h 94 u/n (d'apri3la chruma- lographiil.gaz,•nsr), o:rl.:dcool rst purilh3 par crislal9isatinn rlc sun pII1::d:,U• ueid,-. L,u .a•1 d,• cinr.honiiline dtt phlala4t acidccrutiL,lli.,a. Liru, rlI snu, dl}rluuhlunrnt s'i•ITuctuu par cristullisalions rJpcli-a d:ms dess mclangcsmi~thoxy- cllumol-eau. Par sapuniliiat4uu rbt phtaLdi, IYivngv,re n1,U•un nit Lrerue du tLbh~nLh•rnrnl., un ubtirull In (_..I diuoMhyJl'!.9 cyrl,.p,•ut:uinl dnnl. m,ns :dlnu< prisi<,~r la slructurc eL Rt. ruult;;msrlinn, ahsulla•. rJni saLL qur . ti rdiluntiun d,s nli:oy6_: cydopentnnuncs par lr snduml. L 1'Idr dl dunuc do fa~on pr(•dontiuanlh m1 :dcuull uii I.r mwIhpL• ,1 I'Iq'drnxyle sunl tnmr+. Rnn p:ur rappnrt 3' 1'autrc (.In). Uo Lorut doltc.lk6sIFgitimn.•rnend admetlre, quc d:mslo diini:lhyl eyclopnnlanal qno nmis acuns nbG•nu I'hydr,uplc rI. I,: miL.hylbvoisimsnnLtrans. On n'ust rrpisrdnn I, pns sirr rrflrinri. quc lcs dhn z me1 hyh<s rn " rl :1 sunl.!,murc ,n trnn..puixqur, dtms Ic.e c.ondiliutts dc lo rbdircliun, Ir p•ts.,],u Iru• IPbnolale permrl t'e{ld- mhrisallnn duo mlllicl,• ui rnnduisant: a 1'alL•orrlIr plus sLatilo. Il.a mi:tlhndVr dr•IluucAU' (4) imdiq ue, avrc a.n rnndl'mrntt oldiilu,. d,• Sn,LPe I'hydroxyloa 1'i•nrnm- bremrnLl it I;aucho; rc qni prrrnet,do d6duinc la cmlfrr ^uealiou aL;nlhr (••1I ri-L:dicr.) dcs deux cenLres.r•n pnsitiun et9. Llbxydaliun dcent :dcool dans dis: conditions non cquilibr:nnt,x (3) r:nnduit it une cblone 16vogyro, qpril a utulne spectrn 11t ru snlnliuni rt mOnte tomps.(to rMention ru rllromatograpllii• ru plinsc vapcurq (fne la trnnss dimd- 1hyl-r1.3 ay.inprnlnnnm°rnn:mique dont,nons 6Lionss pnrlis. ll s'npilt dnna. Lirn dcla ('-J trrnrs rlim661rvI-2(IL),a(R) cyr.lbp,•ul:mum•t 1! . 1.a.st(~Hnehimic dos m•~lhy'Irs 2 et!3 n'a pas ctc alfeclMe au cnurs.du Ia nuiln d1,s Irmsformationsut Le (--) dim& lhyli_•;t r.yrlupnnlnuul pn..;,d,- In r.onliguraYioll abeulm: ii:di,tuuc.,•u 13:. (') . Ie• Gil d,• rlmmffnr snuvpnnsiurrsMlnirc In sa141ion nlcn,di• rpm an lorno• d„ pnnr enqlniiin•.r Imsrdt•unt, snlil-:r fnirr, rari,r Ia ,i,nl...+l/rnn ,n, nmlanepl/nM1 r.elllrW5 snl.lrrlnY, nommu ou. penl Ir .t:,lrr par rhnumxlograpLin gnzeuse.snr d!s -. eeh:mtlllnns Pn•IevB.a :, dIR'rn•ulkI iulervnlles. de lemps. Cette LinmFrisnl'Inn rn1 rl,,u•, Ir%vfaeilc.
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282 H. REnncncway G'. Soxxxe.n..It..Gaxslxa :111F,uu. ihn N'unndirifl. zun 111unul.zinigvon. nuW.nulidnn, II,2 m:it All:ylhlnmii,iuwclldn"ridiu, 'f.u Il,ll Mbl BuGmuhd in. 2/I nd Mothylonchlorid wunlon untcr etarkont Riihrcu and h,dt- undlFenchtigkciteaumohlu3 in einer.N,-AtmosphSre awiechem-20 und'-10°C langaam.0,2~Mol aluminiumorganieche Verbindung in 60 ml Methylonehlorid getropft: DaaGemiechscurdbbei der gleichen, Temperatbn 30'.Siin..nachgerbhrt;.anschlie6enderfolgte langsames Envurmen dbe Gbmi- schea.auf 42°C.und einstimdiges Erhitzon imter RuokfluO..Das Athan entwich, bei etwa 10°C!and erlkn;bto.einegute Kontrolle des Reaktionsablaufos. Die f.5sung, wurde nun anC -:0°C abgekuhlt und unter kr5ftigom Ruhren in 150 ml 20prez. Schwefelssurevon-20°Cgegoseonn..DioTempecaturstiegdaboilnichtOber-10°C. Donachwurde dae. Gemisch auf Zimmertempemturcrwiinnt. Anss dor organischenPhaeo Itwseen.sich mit Hilfe ciner.5proz. Nn,C0i-L6sung dib:Sanren isolicren. Eigebnissu s.,Taba-6. Hydricrungg der anra llu-d orhaltanen Siiurogomischo3'.g S6ure und 0,3 g Raney-Nickel wurdon in 100 m1.Mcthanol.bei 70°C und 41at-u I9asser- stoff-Druck in 48td..im,0.6I Autoklav, hydriort:. DiuRoaktion vorlicf nahezu quantitativ, und die Anfnrbeitnngerfolgte nach bakanntnr Art.. Etgcbniase a. Abb.1- . Ozonolyso der aus la-d erhal'.tenon' Sgnregemiache. 4 g ungee6ttigteSuure in 1W mll Nolmn wurden bei -30vG und oiner O„/0,-Gbzehwiqdigkeit von101/Std. ozoniaiert.. Die Spaltung orlblgtee thermiack: [10],, wobei dieUmsetzung quantitaLiv war.und.die Aufklarungdee Gemiecties goschromotographischerfolgte. Ergebnisse s. Tab. 2. Umsetzung:.von4+Methyl-[6-D,]-lioxanolid-(4.I).la' mit (C,H~e)rA1C1 Zu 2;5g (19,mMo1) 1a^ in 20 mlMothylenahlorid!wurden 4',8g (A0mMol) (O.Hr).AIC in Ib,m \Icthylenelrlorid bcil -30°C imtorhalb von S0hlin. und kriLftigom Rfrhrowgctropft. Die Tempert- t,u• dbr Lasnng wurde innerhalb von ~35 Min. auf 42°C.gnbcacht,C danaoh worde 30~ Miam unter R6ek- fla0.erhitzt. Das entweibkende deuterierto A9han wurdeim Gasometer aufgofangen undlmaasen- spektrometrisrh,bestimmt: DieHydrolyee der.L5sung, erlblgtein 10proz. Schwefehuuro bei..-5`C. Ansbcutb0,8 g'(32%d.Th.), Siuregomisch-Mtitllyleeter: ICp. G2-68°C/13'.Tory; nD = 1,43601 Davon sind165PJo, 4-Methyl-[6-D]-hoxen-(4)-annro$.o', r4d-N6fR:. Das(qu) CH-Signnlltiei -1,77 ppmm ist durch: Dooterinm.nicht.nachwoisbar. Nihctieche Messu.ng,dtr Reaktionvon4-Mothyl-docanolid-(4.1) lo mit (C,H,),A1C1 Zu 6,0.g (33' mbtal) dee.Buthnolids 1 e in 965 ml 6fathylenchlorid wurden bie zum. Molverhaltn'v 1:1 4;0 g, (33 mMol) (C,H,),AICI in 10 mt Methylenchlorid bei -80"C langsam getropft. Dse.Ga- miack wurde annschlie6end aufl die entspreehcnde Reaktionstcmperatur gebracht und danach.die reatliche Mengovon 4,3'gI(36,mMo1), (C,H,),A1CI in 10 ml Mbthylenchlorid in.wenigen Sekunden zugegob= 4Piihmnd des Vemuehcswurdo stundig geruhrt undl daa.Abgas mit einem Gasometer gemeasen:. Nach Beendigung dbr Meseung'.wurdc die LSsung 60.Min..untor RuekfluOlgokocht.,Die Ergpbnisse.sind in Abb.2 und in derfolgendewZusammenfassung wiedergegeben. Die Bereehnungder. Geeoliwindigkeitskonetanten und Aktlvicrungaparameter der Reaktian deaButanolida.le mit (CyHr),AICI ergabdie falgmrdon Werte: k, - 10!Tomporatur E;t S* [s] [°C] Lkonl/mol][aal -K-r.- mol+r). 11,1 :L 0,4 7,2 d1 0,2 2,7 ± 0,1 Reaktionen von Bbtanc Umeo6ztuigNa von 4 Dio:enteprochondon den zu 0YU5 Mal llb in I'. Die.Temperatnr det, hahte sich die.Temperu flu0'erhitzt und eech b Literatiuverse[clinis [1]. XVIII.,Mitt.x H. ] [®] H..Rarxasocsr. u. C"x] H- R'aaraeaKs, C 9 (M1074).. [47~ H. R'Enre8oaa4 P. (1970). [5]'~. S. Closox; P. B. Bu. [6]~ H.,Rarxsscsa u. L'rll J. Vtxs~~ u. P..Gax~, C8]i A. V: G§osas n. Tl [9]~~ C. J:.Munasq. E. (I 311, ~ 172 (1969)~,~ [10] F.~.Astxaaa, Bi~ Fs.~ O
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/ 6888 Ji Aln. Chem. Soc., Vol. 1'05, No. 23', 19E3: 8acbsnizadnn of tfs-2!Bu4tryalnproPmeprops"aic AcM(10a): Acid 10a is prepared in 94.4%.(:17:1) stereaisaneric purity as depicted! in the Supplementary. Mamriah' 'H NMR (90 MHi, CDCIr) & 2.47 (g! = 8 Hr, 2 HI); 2.13-1.17 (m, 8 H), f i17-0i83'(m, 4 H),.0;83-0!60 (b a, 2 H); 0.00 to-0.23 (m, I H);13C NMR (CDCIr)',6 180.6. 34.7, 32.4, 28.3, 24.2. 22.7, 16.1, II5:2, 14:1I, 10.8; MS (EI)I, m/a 171 (M' + 1),.55 (q:00%); IIR (film)3000, I720cm-'. Anal. Calcd forCtoHiaOr: C; 70.58; H. 10.59. Found: C, 70.36; H,.10.42. Ihctonizations of: 10m are effected and product analyseaart achieved as.described above for acid' 9s. Ila<todza0on of trans.2-Butyfcyelaproqotlh.eoie Add (16a)- Acid 16Y is prepared! in 98.9%~(87:1) ,stereoisomcrie purity as depicted in the Supplementary Material: 'H NMR (90 MHz, CDCls)'611.90.(b s,. I H);.2.28(d, J= 7 Hh, 2H), 1:60-L.17, (m„ 6 H), O193 (0. J=7Ha, 3 H); 0.96-0.30 (m, 4H);"C NMR (CIDCIj 6 180:2, 38,9, 33.5, 31.6, 22:q 18,6, 14.0, 13.9;,1 L6;:MS (CI) m/z.157 (M•+ 1, 1tN1%);;IR(fdm) 3000, 1720 cm.'. Anal. Calyd for CyH,sOr:. C, 69.19; K 10.32: Found: C,.69.39; H, 10.50. Lactonivation of86a by Method C(as the aorrcaponding methyl ester) in.CCh with use of 2.2 equiv of inemury triFluoroacetate over 19.8 affords mercurated Iactone 18a (86% yield) and trifluoraacelate eater, 26 (9% yield) after fiaah chromamgraphy.(30%othyllstttate in hexane eiution; the Rpvalues,of 18a and 26 in the same solvent are 0:16 and 0.54, respcctively).. IBt::.'H NMR (90 MH'z,.COCIr) 64.30'-3.86 (m, I H), 3106-2106(m„3 H)', 2.16 (d, J= 12 Hz,.2 HI);.2.00-1.20:(m, 6 H), 1.01 (t;1 - 7, Hr„3' H);:'aC NMR (CDCIs)'.6 175.8, 88.4, 40.8, 39:0 38.0, 33:6.27.7, 2A3t 13'.8;,IR'.(tilm):1050.cao'. 26: 'H'NMRs' (90 MH'a; CDCl3i 63.21-4.941(m, 0,3 H),s' 3.74 (di 2 H); 3.38:(a. l'. H), 3.31-1.57 (m„5 H),.1.57-1.16.(m, 4 H), 0:98 (ryJ= 5'Ha, 3IH); I82: (film).1775; 1730 cm-'; MS (CI)) m/i 451 (1100%)6 . 169(80%): Reduction of lactone 18o using.Methad Eand GC analysia:(the rel-ative retention~times'of 18h and l9b a.e 1.26:and 1.0. respectively) shows that afteraccountingjorstereoiiomoric impurities in starOng: material 1'66the lactonization proceeds in aeentiallymtallstereaseleclhdly for intwraion of con6guration. Flash chraautography(25% ethyl acetata ih tie:ane elution):affords quercus lamone B14 (186; 75% yield): 'M NMR'. (90 MHk. CDCIr) d 4:11-3.81 (m, I H);2.87-t.90:(m, 3H), 1.91-IL211 (m, 6 H)„ 1.13'. (d, J= 6 Hz, 3 H), 0.92 (t, J'= 7Hh, 3'. H); 1sC NMR'. (CDCij)4 1765, 87.2, 36:9;.35:9;.33.5;17.7;,22.3,,117.3„1I3.7; IR:(film)'. 1785 an '! Exam msss calcd! for C9Hts0i: 1:56:1 I50: Found: 156:1156. Alternatively,. reduction of the crude cyclization peoducb(iucluding tri - Ouoroacdate 26) using Method' F(LLAH):affords-0iol,24 after flash chromatography. Dial 24: is shown spectroscopically to,be <ssentially homogeneous upon comparison.with authentic:diols.22-25prepared as described in the Supplementary, Material. 22: 'Hi NMR (90:MHz, CDCIr)6:4.08-3.02I(m, 5H), 11.88-t.02 (m, 9 H), .1.10-0:60 (m;.6 H);. "C. NS1R: (CDCIs) 6 75.6', fi1.5, 39.0; 34.1, 311.9, 2914, 22I9, 14!8; 14.0; IR (film) 3330cni'; MS (H[) m/z:75.(l00%); 45 (:78%). 23: 'H NMR'. (90! MHz, CDCI3) 64.23-3A7 (m,.5 H), 2A0-1.03 (m, 9: H),1.17-0!78' (m. 6 H); °C NMR (CDCIy) 6 74.6,61.2,38.7, , 35.4, 32.4, 29:4, 22:8;. 14.0; IR'. (Rlm)13340:cm''; MSI(EI) m/s 75 (100%); 45: (39%). Anal. Caiod for CrHjspr: C, 67.45; Hi 12.58: Found C,.67.24;H, 12.40. 24:: 'H NMR'.(90:MHz; CDCfr)6 3!88-3:08'(m, 5H)', 1.95-1.15 (m, 9 H);. 1.15-0.68 (m, 6 H); uC NMR (CDCIr) 6 75.6. 603, .,. 36.3, 3512;. 34A,28:0;.22.7; 16.5; I4.0;:IR (film) 3330 an ';. MS'(EI):m/z 85'(93%);. 56 (100%). Anal. Cakd far C~HmOt C, 67:45; H;.12.58.. Found: C. 67.53; HL 12.69.. 25: 'H NMR (90 MHz; CDCh) 6'.4120-3.10 (m, 5 H);.. 1.96'-1.20(m, 9 H)„ 1.20-0.73 (m, 6 H);:1°C NMR'.(CDCIs) 6 74.7.601, . 35'.8, 310, 28.6.22.7; 14.0, 13.8; IR (film) 3330 cm:'; MS'(EI) nr/a 85 (100%). 56 (84%). gactmiation!of a3r-2-ButykycNprap..elti.oaie Add (17.). Acid 17w iaprepared in 97.5%.(39:1) stercoisameric purity as depicted in the. Supplementary Material: 'H NMR (90i MHa, CDCIs)6'.10.31, (b a,.ll H). 2.40 (d, A'= 6 Ha; 2 H)l 1.62-1.15 (m, 6H),.0.93 (t;J = 6' Hz:3 H). 1.11--0.64(m, 3'H),-0.05 (m, 1 H); uC:NMR:(CDCIr)'. g 18016„ 33.7, 32.1, 28:4;2215, 15.4, 14.0,11.1!,.I0.7; MS (CI) m(z 157(M«+I1100%)4IR:(Elm),3000;,1710.cm'. Anal. CalcdforCrHispc: Ct 69,19; Hi 10.32'. Found: C. 69:35; H,.10.29:, Cyclization of 17t by Methad' C (via the <orrmponding methyl ester) in.CCI, using 2.2 equiv of Hg(OOCCFr)z affords mea.urated lactone 192 , (56% yield) andltrifluoroaoetate:aater 27 (26% yield) after Bash~chro-matography (35% ethyl acetate ih htxane elution)l. 19a:'H NMR (90 ~ MHz, CDCIr):6'4.66-4.33 (m, 11 H), 330-2,16 (m, 3 H)', 2.02 (d, J- 7 Hz, 2H), 1..93-11.20 (rr:6 H), 0.96(h J- 6 Ha; 3 H)c'rCNMR . (CDCIx)6' 176:3184!0;.39.3: 38.0; 34.1. 29.3;.28.0,.22.4, 13:9; IR (fdm)~ (51) The 'H'. NMR: spectra of: trifluoroacetate eaters 26 and 27 exhibit eanaeuu prain;.thesaignmeuu are reperted es tMy appear.,lle raductioos, af;26 and 127 provide.aurprisingly elean diola 24 and 23,A respsctivdy,. whiob are eorrelated inthe uaual manner(ref 14). CoUum• hloh'amadi, and PJaffock "". 1730cm '. 27: ' H NMR"(90 MHz, CDCis):6!5.27-4.94 (m, 0.7: H) r"~ ~iC.. 3.70 (s, 2;41H), 3.38 (s, 0.3 H), 3:/1-1.541(m, 6 H),.1154-1114 (m; 5 H), ' ' 0.94 (t,!=6 Hz, 3 H); IR'~.(film):1775 '. 1725Icnm ;.MS:(CI) rrr/z 5& , ~ (M'+ 1);.169:(100%): Stereochemiealianalyuca as dbscribed above for ti6 the lactonization of 16Y show theiactonization to he essentiallytmally " stereo- and regioseleative fhr the.formation of iactone 19r. Red'uqion '4iof l9a by.Method E affordsquercus lactone A'4 (196):in 7P40%yieldl };'H NMR'.(90 MHz, CDCI,) 6 4.58-4.28.(m, I H).2:93-I.93 (m, 3 H), -#;y: 1.92-1.20:.(m,.6 H), 1.20-0.83 (m; 6 H); 1tC.NMR (CDCIr) 6176.8,j 83:6; 37:5;.32.9;,29.5, 78.0; 22.4, 13.8; IR.(OHn) 1785' cm '. Fsact mats. '!- calcd forCyH,aOs 156.1150. Foundr 1156:111146... lAc[a:atiaa of [u„O;a} Bioycle(4:1.0)reptaoo-3-nrhoxlilic AcW (28a): - Stereoisomerially pure (>98.0%) acid 28a issynthesizcd as desaibedid in the Supplementary Material: mp 43.5-45.0 °C;'H.NMR (90 MH; CDCIs) 6'.2.50-1.87 (b s, 4I18), 1.83-1.23 (m„3H),J.20-0:87 (in, 211);. 0.83-0.55. (m, 11 H), 006 (dd, J„= 5 Ht; Jz: = 9 Hz; I H);'sC. NMR. (CDCIs) 61811, 37.7;.26.025.0,.23,1, 109, 10:0, 8.4; MS(EI) m/z 140: , (4t°),95'(1L10%);.IR(IBm).3000;,I715em'. Ana1..CalcdforCtH,z0/;+:• C;.68.57;. H, 8!57. Found: C, 68,70; f[ 8.52:. . Acid 28a iseysiized wit'h.Hg(IDrCCFs)x in carbon tetrachloride by~ using Method A(5!days,.25 °C) or MethodB (20 h, 25', °C). Thee resultingorude residum exhibit ihfmredabaorptionfanticipated for ry-: lactone 29'and'blaetone.30 (Rlm; 1795, 1730 cm-L respeetively):.. However; all attempuat Rash ahromatngmphic separation effe¢t da& struction of the6 component: Furlhcrmore;,acidificationi8dlowed by- usual exttaetive: workup of the remaining aqueous'(ayon affords smaH'l amounu'.of hydroxyacid (5-7%)', derivedUromhydroiysis of thelabilce lactanc 38 (shown byindopendent radumion.to diol 32,.vide hdra)i Accordingly, the:worhups and analysesam performed as fo0ows: After addition of eaturated'aqueous'potassium bromide (2.0 mL) and vigorous stirring for 0.5 /4 the aqueous phase is aeidified'to pHl2 wth 48%aqueoua hydFogembromide. FoOowing:exttaetion with chlorof'orm (3 X 2.0:mL);:, the.eombined arganic:leyersare.dmed (Nar.SO4) and concentrated ie.: vacuu. Thacmde residue is submitted directly.to reduction Method F(1:AH). GCanalysisofthe:crudemixtureofdiulss8ows:31l32.=2.5i11 (the relative tatendontimes of.31 and 32 an 1.00 and' L1 llrespeai4ely), ';? . Diols 31 and 32 ®n be.sepamtcd by wmfui Rash chromatography (ethyl acetate elution, 50-W%mmbined yield:from acid 28a) and shown to be idkntical4with authentic sampless prepared as depicted inn the Shpplo- .- mentaryMaterial. 31: mp:100-101°C;:'H~NMR'~.(80MHz,CDC1J) ~ 6 3,45 (dJ J= 8' Hz, 2I H)., 3.35-3•00'. (m, I i H), 2!15-1.85'. (m, 2 H). 1.85-1.35(ny 6:H)„1.30-1.13 (m, 2 H);. 1.00 (d, J= 6 Hz, 3 H);'sd NMR (CI9CI7) 8 76.0, 68.1, 40.3, 39.8, 38.fi, 32;8, 28.8, 18.4; IR.(KBr)', . 3350 cmi':. Exam mass calcd for C~HisOi; 144.11150; Found: 144.1142. 32: 'H NMR (90 MHz, CDCIs):6:3.48(d, J'= 6 Hz, 2 H), 3.40-3.17 (m, 1 H)', 2.27 (a, 2 H); 2.00-1.43: (m,.6 H).1.43-1.13 (m, 2 H), 0.97 (d„J= O.Hz, 3 H);."C NMR (CDCIs):6 74:4; 65,3, 34.7, 32.3, 3, 29.1. 24.5, 18.2;: IR'. (film): 3350 cm-': Exact mass calcd for C.HisOg 144,11501 Found: 144.1146: Cyclization of rram-2'-(Benzyfoxymethyl/-1-nw6hyleyeloprepazu-' propanol(42). Alcoh'o142'upmparedasdepictedinschematicformin the Supplementaay Materialr 'HiNMR: (90 MHz, CDCIj) 6 7.20 (a, 5'. H)i.5.37 (a; 2 H), 3.60-3.05 (m,4!H); 1.79 (s„ I H), 1.74-1.05I (u4 4' H)1.B.94 (a, 3 H) 1.03-0.69(m, I. H), Ot40 (de,J, = 8 Hz;Jt - 5 Hz, I H),0.0f (dd, Ji = Jr.= 5 Hr. l H)p13C TIMR (CDCIt) 6 138.31 1'283, 127,9,127.5.72 16; 70:6; 62:8, 30.2, 29.9,.24.3,.24i l, I9:7,1:7i6; [R'. (fdm)', 3430 cm:';: MS!(CI) m/z 235 (M•'+ 1)t.127(59%):. hhefollowingeydizationprocedhreu'.repreaentative. Cyclirationof -.., alcohol 42 by MethodlA with Hg(CIO4)i:in DME:affords':tetrahydro- furans 43rand 44a aa:a mixture (63%.yield)'% and diola 45a and 46a o' - a mixture (11%yield),after flash chromatography (1.5%ethyl aaeute in hcxane followed by 60% ethyl acetate in hexane elution;.43a and 446 elute first), 43s, 44a:: 'H NMR (90:MHs CDGYr) 6I7:23I(s, 5 H),1.43(s, 2 H)„ 3.90-3',33 (m..3 H'), 3.16(dd, J'i= J4 = 8'Hz), 2:33-11.30 (m, 5 H); 1.77 (d, J'= 6 Hz;,2 H)I (two meth'yl singleu; 1:07, 1.01; l:3 ntio);. -. IR.(film). 1060csn''. 45a, 46a: 'H NMR'. (90.MHz,.CDC1}) 6 7.32 (/;. 5 Hp:4.51.(s, 2IH), 4:06-3129:(m, 6:H)„1L93-1..73 (tq 3 H), 1.73-1.45(m,:4IH)„11.25(s;3H);IR'.(Rlm)'3350mn'. Reductionofthemizlure of tetrahydrofurans 43a and.44a using Method E alYords43b and'44h. in 70% yield after flash chromatography (10% ethyl'acetate in he:aoe elution). . Comparison of tha:mixture withauthentic samples of 431 and 44b.by HPLC (2% ethyl acetate in hexene dution; thu:relative relentiun times ara 1.0 and l. t, respectively) demumuates that the ryeliratioa _ proceeds in only 80%selemi0ity for inversion of con(iguration (47h:46 = 4;1). The spectroscopic d'am far authentic samplea.sre u fbllow: 438:: ." 'H NMR"Q80 MHz, CDCIr)'.6 7:30'~ p, SHL~4.46 (a, 2 H); 3.80-3.62 `~ ;: (m, 2 H);.3'.63-3'.10 (m, 2 H); 2.17-1.46 (m, 5 H), 1.09 (s,3 H)„ 1.04.' (d, J= 8 Hz, 3~ H);'sC NMR (CDCI,) 6 138.7; I'283„127:4, 84.0; 73.1, 66.9; 42.7;,35.6; 26.0,22:9, 13:3; IR (fdm):1080 an';.MS (CI) m/s 235. (M".+ 1,.100%). 44h: 'H NMR (90 MHz, CDCI,) 6.7.26 (a..5 H)', 4.41.,: S7503084
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106 T. Fnig. rra. yield and oaidation of'(V)Igavelattone (VI) in quantitative yield. Dehydratiomof (VI) with poly phosphorie:acid..was:earried,out, and dihyd'rojasmone(VIII)~wasobtained.in 98'°J,.yield. The:ovetap yield of (t-0l) from (IV) was 75%. - Simiilarlyiother I-a1ky13~-methyl-?-cyclopentenoneswere.obtainedlin good yield (Table I, 2, 3 and 4). High yields of cyclopentenone derivatiuesncitH this method are.superior to the yields ofthe k.nownn methods. 4,4-Dialkyl-4-butanolides~ prepared by our method have sweet smellingand'].alkyl. 7'-methyl4'-cyclopentenones have jasmine-like odour. These lactonesand.cyclopentenonesa:_ nry, compounds, andmay be used as.nnc perfumeryy materials: References. I. BOehi,.Gr, Egger. B. J. Org. Ch'eru. 1971. 76, 20•-1L. 2. MtMurrey. J'. E.; Melron,. J. J: Arr:. Chrnr.. Sar. 1971. 93;.5309:. 3. Oshima,. K.; Yamamoto; H.; Nazaki. H. J:, Anr. GSrnr..Snc 1973, 9S, 4446. 4 MuAaiyama, T. Araki, M.; Takei. H.J. Arn Ch.m. Sam'..1973;:95,1763... - 3 DubS P:; Stussi R Hrh: Chim. Arm 1979 61. 990. -6 Fupu. T.t Watanabe S.; SuBai K.: Inaba, T TakaBaua..T.l: appL.Chan. Binmclural: 1978. 28, ®8: 7. EnnASUn, J. L.; Collins Jr. 1. Oryr. Chenr. 1965. 701.1050: 6 Patnekar; S. G., M'arhur„H HL: Bhauachryya. 5: C. lmNnn.L Chrm:.1966', 4, 67:. 9 Stock.G.; Borch, R'..J. Anr Chern. Sua 1964, 86: 935. 10 Fiemr t:;: GenM, J. P; Avrahayrun Lmr.. 1971 1565. 1'.1. Ficini..l:;:d'Angelo.JL:Genll.l:P.:NOir6:,l.Terrrs4nlmnGw...19711..1569. 1.2. Weinreb,.S.:.Cvetoxich, R..T. Trtrnhrdnrrr !p"r. W7?. 12.13. 13. Ellison„R. A~;,Woassneq,W. D. Chcnr: Cnnnnun. 19^.579. 14. Sisido.. S.; Torii, S.; Kawanishi, M. t Ork. fhrn:. 196:; 29, 904, IS Amm. J. H. Patnekar, S..O Muthur: H. H Bhauacgryyn,.S,.C. J'ndinnJ: Chenr. 19641 2..14. 16 Bhanot, 0. S Dutra, P.. C. Cheor. Cunnrmn 196X..1'-'-. 17 Det S.;:Rai C. JralinnJ. fhrm.Sr¢. 1957 34, 66:.. Some As[)eC[t R, sh P. Raval : ,tler...mrgira/ Engineer C9riwrrirp-,/~rnrBar, (puperreeeiheca B/'vr, Remo'•al of in obtall:e.t byq belou'23.K'. regard5theeff tures, The rat, data..4:is cont duringl ,hlorin IlnreCCnt Iim:S. rhC.c aluminium te_inoiogi processf. In c3e proa lo eCtraction `f inetai P "~ •:r ::. -:er - ~riQure II.. Scht-atiec die drier. S. rotame:e.^. 6., rhe. W, silkapaniclel 12, heai N' 0142-0 (J~ . Q
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der Vor~ xter undi CntO hen-lm;. IR:. 18 (-CHa). = 7;8IIz; C=O). g L[AIH.,. ,20 g des I ml. abs, etzto mit Diothyl1 iicltstand uta:98%. mm- I$. H-NMR: <(lin) l,'l0i g einea -Komple'-.. eltiet, bei'a ld 30 min rgetY'emit,, utd NaC)- Lifsung& wurde alb ten: Sdp: 1720 . cm-t' 17 («('sHo);. CgeCHa) (-40H=a)l (6)') wurde beutA nll8 ktionszeit - (COOR)1 da),) t 2,10 = 7,b Ha, ) wurdo in uleatcr ar. o Flilssig- ,, (COOR), 23 (:-OHa) -7s5 Hz, CHa)2O-)I fol~cnd'en ic Univer- nkt „Mns- hemisohen iol.e For. mtsnaon: -Spektren. /1. liornmcxki cl.rd: , ::-Vinyl-1.a-diu~olnuiuui- uad 4-MaLLyI-7•-lruaunimu•tipier.ioe t. N"Or rinr+: llbaixiaht. xiallo: n, 11. 1gnxMnAaor mid M. I liuaxsy Aopuw.. CLoin.. 10„ SL6II1:174J; Angow, Clmn:: fW,.R.d.. Ia, 252 O7174/'„ bM. A. W lxx[x, Oi,g. Mo,,S Shcetrom. 11, I)2l1 [1..U74JL. s I. b1:. Anxltrr;.Aor.nnntxChu,n:. Itirr. n„404 [,1}I7f11L. a J 1i:.,Diwa.und C. Desnnnsl, Org. Mass Spoctrom. 8,, 385 [1972). lFiv oinozusammonfnsaandn Darstollung xinhar. I:. Iixv»si und H. Shax•Atrr., Arngo,v: Chmn. S.v; L89~[Ii870); Am),ow, Chmn. L,t1. Nill Liy, 509 [1976]: auH:., Ban•r.numvlr.•r.,, C. DjEleNSVI und D'. Hl. W/c. l.unMs, Mnes Spccf.romotry of Or;;nuic l.'uinpnund$. Holden•Diw, San Fmuaiaco 1907; 6 W. VBZreni W. Mzlsvrm mnd W. J':: RtCUrsu,. Org.. Maae Spcctm,m. 8, 777 r1970]. '. c. H. F.. Aermsn, M.. Fazxzox mnl J: C. Tnnb+rl, OrF, Mlew ..1'pccf:ro uu. 10, . 178 [ 197:i{i. 607 a. Um. xnluhixl,irmhru4lnpuaru•}pnnuntuu vorinlwaCna, xni Icxt),axkdlt;, dir9 imi ]'rinrip nnchh rmdom, >.n b ixnuu•ro'. emi a jrvliwll tr•nu:Lindoao CLl$pllg!-Toucu ausI tntd :2 vnrlii,ywn kUmltAns dlc zllflllllgnrwcIDO oin uloichrs CA-Spoktram liofcnu Obwold dioear Fal] prinzipiall'niellt ansgosablomen werdvn: kenn, ciwcllnu,t.cr ad'gnmd nllhr bisharpnblia.icrten CA- Arl'acitm,. achr umonhrsohcinlioh zu ecin... . 7 IC.lt. ,7xxxlxoa, in ]i,. IBoxvsrrund J. C:. DAVIS ( Hlxg.); Semo~ Nmvor Phyeiall Mot6oda'.in Stniotnml Chornixtry> 8..105, United TrvdoPYVas, London 1lifi7. r D. VonnXxnaa, LiobiFsAnn. Chem• "_94j.2.53[18971• 9 D. 9+L, Jmxss rmd G. Txrrr.rvtwnc,J. Chmn. Soc..S•S, 1691 (1904). ie J. C.. CoL.mNn icnL W. W. Husn,Org., Syntir. fi2„ 5 11972). ..
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390 Farercett' and' Gibson: The Influence of Pressure on lll is.iutcresLiugLu nu.LC thut re actiwts wtlich proceed uL aLucusphuriec ptessurcuttlyii[ tile presence.of aluminium chloride, showed no.signs of procceeling at pressures up to.JU00 atm., either inn the absence of.catallysts or m4he'.presence of mildiacid or basic eatalysts... Beforee the observed pressuree effects can be ascribed to one or mom . of thee possi6le influences aireadydiscussedl, it would seem necessary both to extendd thissurvey too dis'. cover how fartheeffects.r are general and hold for all reaetions,, and to undertake:a compre- hensive quantitative study of these effects. EXPEAIMENTAL. The appamtus'..used is shown in the fig.. The reactants weree placed in small glass tubes of' 10-15 e:e. capacity, which were inverted with the.open: ends under mercury contained in glass liners fittinginto.the steel pressure vessels as showm. These vessels'were plhcedd in oil thermostats maintained at the required temper- ature, and pressurewas transmitted to the samples.under investigation through.the.memury by means of a light',mineral oil, the pressure of:whiehwaameasureedbymeans of calibrated Bourdon gauges.. Thepressure.was obtained either by means.s of a~ Cailletet-type screw: press . designedd by Dr. A. M-ichels' of the Universityy of Amsterdam,, and. built tiy.Dikkers & Co: of HeqgeIo,. Holland', or by means of a hydraulic intensifier designed andd built in thesee laboratories. The few experiments recorded whichwere madee at pressures above.. 3000 atm. were carriedd out.in an apparatus smilar to.that..described byBridgman. (•• Physics of'. High &iessum;' p. 42, Bel7, 1'931).. alsodesignedo andd built iathese latioratories. (Engineering, 1933, 188,. 32):, Cheek experiments'.at about atmospheric pressure. were carriedd out alongsidethee pressure experimentss either in sealed glass tubes„ or in small tubes'.inverded over mercury, as. described above, placed ialbw-pressure metal vessels.fitted with spring-loaded relief valves set' at about 5'.atm. Some trouble was at first expericnced with the fracture of the.glasse reactliom.tubesafter onee or two applications of pressure. Theglasse flaked awaylrom:.the inner surface and produced.a structure honey- combed with..fine eracks: This phenomenon isno doubt.due to the penetration of the,e glasss by the organic lyquidss under.r pressure. (cf: Poulter„Phyaical Rav.,1932;.40, 877). It wa.a found that tubes.mades of Pyrex glassliad a much longer.life than those of soft: . glass. Reaclions'.Setmeen Aiid A'..nlrydrides.s and Aromatic Flydrocarbons.- Ma7eic anhydrideand hydrorarbons. Attempts to detect thecome bination of maleic anhydride (LI mol.)with benzene, toluene,, orr naphthalene(1 moL) were unsuccessful, the anhydride.being recovered.d substantially unclmnged'.. The reactiansweree investigated up to180^ and at 3000atm...forperiods upp to, 40 houm.. The: anhydride, however, underwentt slow decomposition on being heated far l'ong periods at.180", carbon dioxide being evolved whilethee anhydride darkened; extraction of the residue with.benzene left a.spariaglysolutile brown.n powder which liass not beenn identified'.. This denomposition.ispossibly analogous too that of', succinic anhydride(M1lolhard„Annalen, 1889,.253, 206, 233; 1891,.287, 80, 94;', Bredt, ibid., 1890,. 256,.330):. The reaction between anthracene and maleicc anhydride, which proceeds at atmosphericpressure at.200" (Diels, ibiiL_ 1931, 486, 191); was not studied.under pressureowi¢g to the high.h m. p.'s of the reactants- It was, however, found that the n:zctionn procer.ds'.at a'moderatee rate . at ordinary pressures'in.toluene solution,.and theeffecte of pressuree on the yield.of'd the condens-ation,product was determined at 60° and 40°. The.yield was determined by adding the.product . to water, basifyingg with 10'/0% sodium hydroxide, andi heating to. 80° Eu• } hour to decompose the anhydride.. The.toluene layerwas then removed, and the acid'.precipitated.by acidificattion with.hydtrochloric acid (Congo-red), dried at 100°;..and.weighed.. The yields were identical at 30001atm: and at atmosplrteric.pressureat 6o°, whilst in l6 hoursat 40° tlleyielfle at 3000,atm., was.20%'. due to tl PFIhh anhydri" to 1509 presenu might b hot sodi acid. (idlwas the Raac' Benrald hours. wav det ether, rr desiccat. The 8rs's observe Dimethy Benuldt'Benaolc: Tempera Prewure, Time: hr Yield' ¢ claik l. By. proport" pressure more th. The caus wl distillat. J. Ina.J The solution bensoic benzoic trol. T by the a Anr ducible determii . in glass It.wou4 the rate thatt pe:': intllec 9488). expanm Moa gated at. pressurec nsafhawt H.,7•4;fff The aldebyd' similar "
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J:.Am. Chern. Soe: 1987, 109;,1249-1250 ]/1'249~ FSgure 1.Structure of the diaro0uorene adduct 10 aC(E,E); 1,5-cyclo- acladiene (one eoantiomer). Bondlengths and angles of eight-membered ring;, 3a-4d54.5', 4-5'.154.8„S-6 14816, 6-7 1323, 7-814817;.8-91155.3, 9-9a 153'.9; 9a-3a 156-0 pm; 3a-4-5: 115.oP;.4-54 106!4°,.54-7123.1°, 6-7-8 1122.4°;,7-8-910611, 8-9-9a Ia4.2°; 9-9a-3a 119.4°.. adducts:wereseparated in eaah.case. From the structure.proof of ltr given below, we.deduce that in alli four cases we were dealing: with 1:1 mixed crystals of l diastereoisomers,, lhisfoiling.potential distinction of derivatives of Ia and 16 by their "C NMR spectra. After the failure of the "number game" we resorted4oX-ray analysis of a crystalline monoadductof 1. The structure of the diazofluorene adduct'10 (Figure.l),10eolorlbss monoclinie prisms,., reveals provenance from the twist form ]s.. The angle of 69.4° between the 6,7- and! 3a,9a-bond (Figure 1) indicates that thee monoadductisstill:frxed..inatwistconformation: Notonlythe. 1,2-bond of (E):-cyelooctene but.alsolthe.5,6-bond°isstericallyeonstrained; force field calculationsda show a preference of the "erown" (heretwist) overthe.ctiairform~by 4.U1cal mol'' and.. Dld°'= 111.6 keal mol`' forthe."jump rope.rotation" at the 5,6-bond. The corresponding rotation of the 3a,9a-bond in 10 is; blocked by the.annefatede pyrazolinec ring: The dihedral.anglb (5fi-7-8)~ a0the trens double bond of 10: is 136.3°, as compared with137:7' fbundlfor (E)-cyoloocten-3-yl 3,5-dinitrobenzoate (X-ray)'2 and 136.0° for gaseous:(E)-cyclo- octene (electron difftaction)'.° Out-of-plane bendingi(j<='24.0°,. 28!1P) and torsion.(I7,7°) in 10 participate to.asimilar extenrt in the deformation of the double bond as in the other models.. The tHNMR spectrum of Is in CDCI3 at.0 °C shows twoo broad signals at. d 2.6-2.9 and 418-5.2' in the tatib:2:1. Irradiation. at E'2.45 furnishes.a sharp.singlbt at.b 5.05, demonstrating.theequivalenceofthefourvinylHs. Two°CNMRsignalsat;d.32.3and1141.1 confirm the symrrfetry.. The following bc values (CDCh) and(in brackets)'. J(' sC-H) of the olefinic Catoms of cyckoctenes s and 1,5-cycloocmdlenes suggest.a relation with ring.strain:'. (Z) 130.1.(154.D), (E) 132.8 (1'51)j (Z,Z). 1:,28.6:(152.7), (E,Z)a36.0;. (E;E)-141.1 (1:46Hz). Strain:energiesaccordingtaforce-field. MMI:r•1e'(Z)'.5:3, (E) 13.1. (Z,Z)' 8.3, (E,E)~20.3:kca1 mol-'.. T ) Ci,HmNi• monaclinic, P2i/c,.a=13.797,(3) A, 8- 15.173 (4) A,., c- '.697r(4) A; @= f09.42y2)°, P= 330P A>,.z = 8(Rir of enentidmen in es}+mmevic unit), Da,. = 1.21 g.cm 0.66.em,f, Ma Ha, wluders . priams, Oil5' x 0:21 x0.30 mm, Syntex P3 diffmttometer graphite.monae chromator, 2 < 28 < 45°, ,oscan, 2'-29.3°/min; emrettion for intensity var{etion of eheckrenexibn (3%): 4936da1a colkaed, 4'316 unique and 3275'observed (Ji 2c(1)). Direcrmethuds solution, MAchd cascade refinemenl;C all non-hydrogen atomsanisotropie,. hydrogen atoms refined with f'sxed' isa tropic U approximalely u2U;v of corrasponding carhon etmn.. Rr= 0.0819; R,r= 0.0674, highest difference map:peak=Q248 e/A?; number uf refined parametera529;,ratiod'ataJparameters6.2: Comparablebondlengthsandi bond anglaof the two species can becostsidered!aequivaknt within.the 3. criterion, but numerical valua for the molecule depicted in Figure 1Lmatcb more closely standard .m3uess than Ihose for the other iromer. (11) Binseh, G.; Rober0. 1. D. J: Am. CAem: Soc. 1965, 87,.5157.. (12) Ermer, O. Angew. Chem., lnr. Ed. Engf:.g974; 13, W4. (13) Traetteberg, M. Aesa.Chem.,.SeeB.l975; 29; 29. (a4) Allinger„N. L.;:Tribble; M. Milkr, M. A.; Wen; D. H. J: Am.. Chem. Soa 1971. . 93. 1637. (15) Atomic coordinates found in thesapplementnrymaluiai am alsodcpositedat0 lhe. Cambridge Crystallographic Da1a,Center. Af1r/A,[!1/I, Acknowledgment.. W e thankDr. D. Mannig far assistancee in the X:-ray workandl express our gratitude to the Fonds.der Chemischen Induslrioforsupporl. Supplementary Materiall Availahle: Tables of atomic caordi-nates;!' bond distances, bond angles„parameters.of anisolropic'c temperature factors, and hydrogen coordinatcs (6pages); table: of caleulated and observed'slruclure factors (20 pages). Ordering, information is givenn on any current masthead page. 1,2-Asymmethic R'earrangementss in Chiral' Sultinrylcyclopropane Systems:. Asymmetrir.Synthesis:of a,a-Disubstituted Cyclobutanones KunioEiiv;• Hironori Nakamura, and TakashiAnzai Department of Synthetic Organic ChemimaryTahoku Coffege of Pharmacy 4-4-1 &omatsushima, Sendai,. Miyagi 983, Jupan, . Receiaed'July 2, 1986~ Revised Afanuscriyt ReceluedDecember3, 1986. CreaGonof asymmetric quaternaryy carbon.atoms' is:one of thre mostimponlantt problbmss for theenantioseleclivee synthesisz of natural products such as steroids, terpenoids, andl alkaloids:. Wee wish to communilcate: a potentially valuable methodd for enaro tioselective creation of quaternary. carbons by thermal 1,2-asym-metdc reanrangementsin cyclopropanesystems possessing~ a chirtl, sulfinyl group on.the rings.. The.thermal.rearrangementsin cyclopropane systems have received much attention in recent years for the preparation of various kinds of synthetically valuablb compounds;3 however,.nowork'hasbeen reported on asymmetric rearrangementsin sueh ~ systems. This.paper presents the first example of asymmetric induction in thermal.rearrangementsof cyclopropane.systemse affected by the chirality of optically activesulfoxides.. Addition of the m•carbanion of (RS)-(+)-p-toluencsulftnyl-cyclopropane (1) (100% ee),4 generated by. treatment of (RS)-(+)tl withh n-butylliehium;, to acctophenone (2a) i al -20 °C for 4 h afforded.(Ss)-3a in 78% :yield (ratio of the:diastereomers, 3t2).. W hen, (Sg)i-3a obtained was heated inn relluxingl benzcne for 3.5 h in.tFie presence of aa catalytic amount of p-toluenaulfonie acid„ it underwent a 1,2-asymmetric rearrangement. to:give (Ss.4R)-4s in 88% yield. Reduction of the sulfoxide in (Sg,4R)14a was carried 1 out by treatment with acetyl chlorides ibdichlbromethane at room I temperature for 2'h, affording (R)-(-)!5a ([a]'So,-14L7:° (c2.0, EtOH)) in 78% yield. Isolatiomof thediastcreomersof 3s wass succrssfullyaccomplishedl by carefull preparative thick-layer ahromatographyoversilica gel (CHC11-EtOH 25t1). Thesamee sequences'.of each diastereamer of 3a were carried'd out byheating: in benzene in the presence of a catalytic amountt of g-tolucnc-sulfbnic acid and treatment with.acetyl.chlbride under the same oonditions to give(R):-(-)-5a having the same optical rotatiomass dese[ibed.above: Hydrolysis of the enol thioether (R)-(-)-5a~ obtained was performed by treatmen[with titanium(Ik)chlbriide (3 equiv)-lead hydroxide (3equiv)-Hh0'.{6equiv)°'in acetonitrilee at room tbmperature for 1'88 h to prodvice.(R)-(-)-2-methyl-2- (I) Martin, S. F: Tesraaedmn.198g; 36, 419. (29For leading references onasymmetrie synthesu, ses (a).Inch. T. D., SyntBesis 1970, 466 (b)' 8eott, J. W.; Valentine, D., Jr. Sdence (Wurhidglon... D C) 1974;,f84, 943.. (c) Valentine, D;, Jr.; SEOII, 7. W. Syarhesrr.e979..329. (d) Drau; K.;.Kleemsn, A.; MarlEns; T. Angew. Chem., lm: Ed. Engf. 1992, 71, 5841 (3) (a) Trost, B. M.; Kedry; D. E.; Bogdanowicz, M. J: J: Am: CAem. Sac. 1973,',95, 306g. (b)Trost. B. M,':Keeky, D, E. J. Am. Chem. Soe. 1974. 96,. 1252. (e) Tron, a: M. AerrC6em. Res: 1974.7, 85:. (d) Trost, g. M, Keeky,.. D. E.; Arndt, H. C.; Bogdinowidz; Ml J. J. Am. Chem. Soe'. 1977; 99,.30g8., (4) Johnson, C. R.; lYniga, E. R, J. Am: Chern. Saa 1975, 95„9692., (5)Numala, T.; Oac,B. Chrm. Ind: (Lcmdon) 1973, 277. (6),(a) Mukaiyama, T.: Ksmia; K.; Takei, H. 8u11, Chem~ Soc: Jpn. 1972„ 45, 3723. (U):CoM1rni T.; OUdletse, D; Daniewski,. W. M. Terraaedron /tsr.. 1978:5063. . .-T.K ., /ici'f,'d P7,34 '

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