-, I 1871 (196S).1 lRcpriated lroo thc tournrl ol the Aqcriceo Cbeoicd Society,91, ottlc(. Copyright lg0g by thc Aoericao Cheoicd Socicty rnd reprintcd by perrnirsioo ol thc copyright Reactionof Lithium Dialkyl'and Diarylcuprateswith OrganicHalides GeorgeM. Whitesides,Williary F. Fischer,Jr.,Joseph San FilipPo, Jr., RobertW. Bashe,ild HerbertO. House Reactionof Lithium Dialkyl- and Diarylcupratesw'ith OreanicHalides'' Filippo. Jr.,3 George NI. Whitesides, lVilliam F. Fischer, Jr.,3 Joseph San Robert W. Bashe, and Herbert O' House ContributionfromtheDepartmen|ofChemistr-I.' 02 I 39' MassacltttsettsInstitute of Technolog'" Cambridge' Massachusetts Receiced Februurv 7, 1969 (R,,CuLi) aryl iodides in ether solution by competing Abstract: Lithium diaikyl- or diarylcuprates react with high yieldsof the coupled product meral-halogenexchange and coupiingreactions. Using appropriatereilgents. procied to completion in the presenceof an R-Ar can be obtained by allowing tt. meral-halogenexchange to speciespresent.in solution with nitroben- excessof R,:CuLi,and oxidizingthe resultingmixtr.rre of organometallic and diarylt'tlprates;it fails with di- zenc or oxygen. This reactionsequence works w'ellwirh lithium di-n-alky'l- react with ar."-liodides only by metal- sec-alkyl-and di-l-alkylcuprates. Although most alkytlithium reagents converts aryl iodides to ar-vlmethanes' halogen exch.nge, methyllithium. uncompiexedwirh copper. smoothly to take placewithout significantmetal- Coupling olirhium dialkyl- and ctiary,l.upr",.swirh rrl,(rihalides appcars (-)-(R)-2-bromoblttltne occttrswith the pre- halogenexchange. The reacrionof lithium diphcnylcupratewith un Sr2-like displacenrent',.coupling <jominantincersirn of configurarion(84-92'T, srereoseleciiuiryl expected of yielcl: thost invohing r-alkyl halides rcactionsinl.olving an rr-alkylhalideiis onc reuctionpartner iroceed in high with n-alkyl halides' A number of fail. Lithium di-n-alkyl-,r3i-sec-alky.l-, and di-r-alkylcopperreilgents ult coiple of the couplingreactions preparationsfor rcpresentarivecopper(l) are complexes are desJribed.and the sensitility and to the presenceof lithium halides' to the merhodo[ preparationof the ate complex.to the narureof the solvent. trialkylphosphines.and diaikyl sulfi<jesin solutionare discussed' relativelyunreactive toward simplc broadly applicableprocedure for couplingthe or- sium reagentsare A reactionwith activatedha- ll ganic moiety of an organometallicreagent with elkyl and aryl halides: thcir to nrixturesof products.T'EOrgano- that oi an or-qanichalide would be a usefulmember of lides again ieacls compoundsexhibit low reac- the class of reactionsavailable for the synthesiso[ zinc anclorganoaluminum €.8., n-alkyl halides' At present'thc carbon-carbon c bonds. Un[ortunaiely'the com- tivity toward, structuralfactors responsible for low nucleophilicityof RM + R,X_> R_R,+ VIX (l) theseorganometallic reugents toward carbon are not o[ the monly encounteredorganometallic derivatives entirelyevident. as rea- main group metals appear to be unsiitisfactory In contrast. organometalliccompounds containing gentslor effecting the formation of carbon-carbon carbon-copper(l) bonds provide a class of reagents a carbon- bonds by nucleophilic displacementat whoseuseiulness in couplingreactions with organicha- reagentsare halogenbond. Although organolithium lideshas beenamply demonstrlted in certainspecialized nucleo- stronglybasic, they appearto be only weakly circumstances. itrut reaction of copper(l) acetylides philic ioward carbon: reaction of an organolithium with acetylenic,earomatic.r0 vinyl,[a'b and acyFr" ha- io*pound with an alkyl or aryl halidein hydrocarbon .,Grignard of Norr- or..ih.r solutionsusually leadsto mixturesof products (7) NI. S' Kharasclrand O. Reinmuth' Reactions Inc', Nerv York' N' Y" 19)l' metal-halogenexchange.t a metallic Substitnccs,"Prentice-Hatt, derived t'rom competing Chapter16. 'ts metalation,s elimination,and coupling,with the last (8) Normant has reported that use of hexamethylphosphoramidc i3 to proceeding,at leastin part,through soivenrfor the reactionof alkyl halideswith Grignardreagents leads reactionapparently products; however'the generalin' Organomagne- syntheticatlyuscfuI yietdsof coupled a complex free-radicalmechanism'6 o[ this solvcnteffeci has not yet beendcmonstrated: cf'H'Normant' Chent.lnt.Ett. Eng!.,-6,10'16 (1967); J' F' Normant' Bull' Soc (l) supportedby crants cP-2018 and GP-i266 flrom thc National Angew. Chim.Fr., 1888(1963). ScicnccFoundation. (1961); (9) (a) G. Eglintonand W' NlcCrac,Ac!can' Org' Chem"4'225 (2) Supporteciby RcscarchGrant No. AFOSR-68'1518lrom the (b) H' Schdnoloskv,E' Inhoffen'and G' Grau' Chent' of ChemicatScie nces, Air ForceOffice ot'scientific Research' F.Bohlmann, Diicctoraie (1961); (c) R. F' Curtis and J' A' Tavlor' Tetrahedrort (3) NationalInstitutes of Health PretjoctorrlFcllow, 1966_1969. \ir.,91,794 (195t); D.E. Lett.,29l9 (1968). i,fi n. G. Jonesand H. Gilman,Org. Reacttons,6,339 C' Orvsley'J' orz 743 (1961); (ttil fa) C. E"Castro, E. J' G'rughan,and D' Appicquistand D. F. O'Bricn, J. Arner. Chent.Soc., 85. ibid"28' Chem.,3l,-t071 (1t66); (b) C. E. Castroand R' D' Stephens' H. L S. Winklcr and H. Winkler, ibid.,EE, 9U' 969 (1966)' (196-<); 2163(1963): (c) R.E. Deisy and s. A. Kandil,ibid.,30.3857 (5) W. l(irmse,"Carbcne Chemistry,"Acadcmic Press' New York' C" (d) R. E. Atkinson, R. F. iurtis, and J' A' Taytor' J' Chem'Soc" N.Y.,1964;G.l(iibrich,Angew'Chem'Int.Ed'Engl',6,'ll(1967)'and J' A' i;'s (tsozl: (e) R. E. Atkinson, R' F' Curtis' D' M' Jones'and referencesin each. Taylor, Chem.Commun.' 718 (1967)' (6) H. R. Ward,J. Amer.Chem' Soc',89,5517 (1967); H' R' Ward (ttl J. Burdon,P. L' Coc' C. R' Marsh' and J' C' Tatlow' Chent' and'R.G.Lawler,ibi(t.,89,5518(1967);C.G'screttrsandJ'F' tol V' I' Comntun.,rzss (b) L. Yu Ukhin, A' M' Sladkov' and Easthrm,ibid., 88, 5668(1966). tl96il; lVltitesitles. et ttl. I Lirhiunt Diulk-t'l- untl Diurylcuprute Reuctiltns 4872 lideshas been used successfuily in formationof a bonds. the significantincrease in thc-yield and a number of arymethane.h- of thermallystable arylcopper(l) rea- ser'ed on oridation gents of the reactionmixiure indicatcs havebeen observed to couplewith aryl.'alkyl.and that r'r'rr at leasttwo reactionsare takingplace in solutio': acyl halides. unf ortunately.the usefuinessof most a reactionleading to coupring(.q 2 or 4), and anothcr uncomplexedalkylcopper(l) reagents in couplingreec- reaction involving metal-halogenexchange between thc tions is limited, since these compounds decompose aryl iodide and rhe cuprateI which comletes wirh (rrr thermallymore rapidlythan they reactwith organic ha- precedes)the coupringreacrion (eq 3). The lides. However, previouswork with oxici:rrirc organoJopper(t) conversionof a "mixeci" lithiur ph"nylmethylcup*rc conrpoundshas demonstratedthat formation of I : I (represented "ate" schematicallyby 2) to tolueneon oxidation comple.resr{of thesereagents with organolithium Phl + (CH'),CuLi--> and organomagnesiunrreagents simultaneously results PhCHr * (CH,Cu) * Lit rlr I in a stabilizationof the carbon-copper(l)boni toward Phl (CH,I:CuLi thermaldeconrposition and in an increasein the nucleo- + =- lPh)(CHr)CuLi* CHrl (-rr phiiic reactivitytoward carbon of the organicmoiety I 2 r.i, bonded to copper. 16 Thus, 2 --+ phCHr lithium Oiittyt- or di- + CHII * (CHrCu) {rr arylcupratesappeared to be of interest ,.og.nts for --> 2 * O: PhCH3 (_i carryingour the displacementof halogen"t at cirbon ) by (eq organicgroups. 5) is in accordwith the resultsof previousstudics.r, ln an effort to This paper reportsthe resurtsof our examinationof estabrishthe most satisfactoryexpc.- mental conditions thc' reactivityof lithium diorganocuprarestoward or- fo.rcoup_ring organocopper re'ge r[: ganic wirh ary'lhalides. halides. The resultsof similar,rindependent in- and to definethe iffect oi tt. rerminui oxidation 'estiqationshave recently been described by Corey and on the y'ieldof coupleclproduct, we havc er- amined Posner,17and severalapprications of thesecbupring pro- the reactionsof lithiur'dimethylcuprateand rc_ lated ccdureshave been reportedsince the origin.i a.iirip- substanceswith ioclobenzeneand l -iodon'prr- tions.r, thalenein detail. Three preparationsfor solutionscontaining ,.lithiunr Ii esults .. dinrethylcuprate"are available (eq 6-g;.ri:,, Thcse Ileaction of i\Iethytcopper(I) Derivativesrvith Aryl :CHrLi * CuX-_> (CH,r):CuLi Iodides. + LiX (r,r Pure lirhium dimethylcuprare( l) can be prepared I b,v dissolving halide-tieenrethylcopper(I) in CH,Li + CH,,Cu-> (CH,r)rCuLi (-/t halide-freemerhyllithium solurion.r; Reactionof this I nurterialwith aryl iodidessuch as iodobenzeneor l- lCH3Li -__+ rodonaphthalenein ethersolution at roonr temperature * L.CuX (CH,):CuLi.L+ tiX (s) t'or periodsof 8 to 2-t hr, folrowed by preparations hydrorysis,yields differ in convenienceand in the properties thc'corf€sponding arylmethane with a maximumcon- of the resulting organometallicreagents. The rn()sr rersion oi 30-501[ basedon rhe aryl iodide. If the amenable to large icale synrheticipplication is thc organometalliccomponents ot' the reaction mixtures direct reaction betweennrethyllithium and copper(Il ;1rcoxidizedrr prior to hydrolysis, the yieid of aryr- bromide or iodide suspendedin ether(eq 6). The conr- nrerhrne is incrcasedro 60-70% (Tablts I and ril. positionof theseorganometallic solutions is not wcll Theseobserv'ations suggest that lithium dimethylcuprate definedon two counts: for one. the,vcontain variubre rs relctivetoward