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Reaction of Lithium Dialkyl'and Diarylcuprates with Organic Halides

Reaction of Lithium Dialkyl'and Diarylcuprates with Organic Halides

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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 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 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' exch.nge, . 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

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 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- 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 carbon- bondsin a sensethat amounrsof lithium halide:for a second,they appear [() leeds to carbon-carbon bond formation. However, be significantlymore activcin certainreactions than so- lutions Corshkov,Zh. Org.K!iy.rO,?t tl96g); Chem.Absn.,6g,7S621l96g); conrainingpure lithium dimethylcuprate(ttd,, rcrA. It. Sladkov 11<{1.._R._Gol.ding, Zh. Org.Ktim.. f,'tjtS (1967); infra). Preparationof pure rithium dimethyrcuprate Chem.Absrr., 67, 9376 ,l967). b,, (l:) (a) reactionof methyllithiunrwith H. Crlman.arrtJJ. M_.Stralcy, Rec.Trac. Chirn.pa1,s_Bas,55, a slight .*i.rs-of pur., sll (1916);(b) methylcopper A. E. Jukcs,S. s. Dua,ancr H. cirn'*, l. drgano^eror. (eq 7) leadsto lithium halide free Chem.. "Sire.ppard, soru- 12, Pl.l. P.l.l(196g); (c) A. Cairncrossand W. n. tions containing an organocopper J' 'lrner'Chem. soc.,90, (r96g); reagentof well-clc- 2rg6 (d) M. Nilssonand o. wenner- fined stoichiometry, strom. TetrahedronLett_ 33070963); (e) for a recent.*i"ru, but is relalivelyinconvenient in irs \rlsson, see NI. Srensk.Ketn. Titlski.,90, l9Z itSOat; Chem..lbsrr..,69, gl45 requiremenrthat methylcopper(r)be preparedin a sep- r I963). arate ( ll) Evidcnce step. Reactionol' methyllithiumwith an ethcr- for coupri.gberrveen aryrcopper(r) compounds and h'rlides arvr solublecopper(l) h;rs bcen fouud irr stuciiesof ttre uri-an ,.".iion, halidetrialkylphosphine or bis(dialklI F.rnrr. Chem. j i;;';r."i: Rec.,64,-6l t1964); (b) C. Bjdrkluncl,rnJ.vt Nilsson, sulfide) complex resultsin a solution containing TetrahedronLetters, (t966); ti.,. 675 M. Niisson, ibid., 679(1966), (c) A. H. phosphine Lcnin and T. Cohcn, or sulfideligand and lithium halidein ibid., 1531(1965); (d) M. Nilsson. Aua Chem. iaci- Scan

Josynr,l ol' t/re .lrtrari<'uttChentiutl Strcietv 9l ; t7 Augusr I J, 1969 Table I. Reactionof Lithium Dialkylcuprateswith lodobenzene" Recovered - iodo- Other solution Reaction , - Yield, 7o'- RrCuLi components(concn, /v/) time, hr 7l Product Hydrolysis Oxidation" l. (CHr}CuLid I 95 3 4 75 6 l6 1{ l5 36 AA 48 42

The presenceof theseligands and their reactionproducts taken to avoid contact between the reaction solution during the work-up of reactionscarried out on a syn- and oxygen(from the air) in the reactionsinvolving a theticscale has consistently proved to be a major incon- nonoxidativework-up, the possibilitythat some por- venience. tion o[ the tolueneor l-methylnaphthaleneformed in Lithium dialkylcupratescontaining primary alkyl these experintentsarose from unintentionalreaction groupsother than nrethylcan in generalbe preparedby with an oxidant cannot be rigorouslye,rcluded. The proceduresanalogous to those of eq 6, 7, and 8, al- increasein yield of unsymmetricaldimer on oxidation though the solutionsobtained by the procedureof eq 6 provides a qualitative measureof the quantity of aryl- may containalkyllithium reagent in appreciableexcess metallic reagent presentin the solution. Additional of the stoichiometryrequired by the formulation R:- evidencefor the presenceof an arylmetallic interme- CuLi. Grignard reagentscannot in generalbe sub- diate is discussedlater in this manuscript. Sincean ex- stituted for organolithium reagentsin the procedureof cessof lithium dimethylcupratewas usedin all studies, eq 6. We have onlr' beensuccessful in preparingwell- and sinceoxidative coupling of mixed lithium diorgan- characterizedsec- and t-alkylcopper(l)reagents by the ocupratesseems to give approximatelystatistical yields procedureof eq 8. The proceduresexemplified by eq 6 of symmetricaland unsymmetricaldimers,re the prob- [with copper(l)bromide], 7, and 8 werealso satisfactory ability of symmetricalcoupling of the aryl moietiesof for producingether solutions of lithium diphenylcu- two arylmetallicreagents under oxidativeconditions is prate. much lower than the probabilitv of unsymmetricalcou- The products of reaction of lithium dimethylcuprate pling. with iodobenzeneand with iodonaphthalenewere in- The data of Table I summarize observationscon- terredfrom a comparisonof the glpc tracesof two ali- cerningthe responseof the yield of toluenein coupling quots: one aliquot was hydrolyzeddirectly; the second of lithium dimethylcuprate with iodobenzene to i.I wasfirst oxidizedusing an excessof molecularoxygen or number of types of changesin reaction conditions. nitrobenzene.and then hydrolyzed. Using this ana- The reactionoI purelithium dimethylcupratewith iodo- lyticalprocedure, thc yield of tolueneor l-methylnaph- benzenein halide-fireeether appearsto be complete in thaleneobtained following the nortoxidativework-up 24 hr or lessat 25o. The yield of toluenein the non- presumablyprovides a measureof couplingtaking place oxidative work-up, and the increasein yield of toluene by sonrecombination of reactionsrepresented by eq 2, on oxidation.demonstrate that the productsof carbon- 3, and -1. Although it number of precautionswere carbon bond formation and metal-halogenexchange

lVhiresitles,et al. I ! ithium Dialky'l- unclDiarylcuprare Reactions II. Reactionof MethylcopperDerivatives wirh r-rodonaohthalene

l-lodonaph- Other solution Reactron _yields. oto ---. Copperreagent thalene componen(s tlme. l-Methyl- l-Iodo- (concn. /V/) Concn, rVf (concn, ,l/) hr Naphthalene naphthalene _naphthalene (CHr)zCuLi (0.38)b 0. l3 0.5 25 l0 67 2.O 5l 29 t7 4.0 58 3l 6 8.0 62 JJ (CH'):CuLi (0.38)" 0. l3 LiI (0.3e) 05 72 ll 7 1.0 73 l3 3 2.0 77 t4 23 69 20 (CH')'CuLi (0.32X 0.ll Lir (0.32) 2.5 59-70 26-28 3-10 ti (2 62 l0;a )< (2 57 l6)" 2.5 (4 70 4)l CHTCUP(rr-Buh(0.38) 0.r3 0.5 I 8 9l 2.0 I 3l 68

4.0q 5 75 J CH.rCuP(rr-Bu)r(0:38) 0.l3 2.0 2 JJ 65 CH,CUP(rr-Buh(0.38) 0.13 LiI (0.38) 2.0 20 29 5l Bas€don " l_iodonaphlhalene. Reactionswere carried out in ether solution a! 25' unlessotherwise indicated. ! prepared by dtssolvrng halide-freemerhylcopper(I)inhalide'freernethyllithiumsolution(eq7)..Preparedbyreacrionof2equivoimiilyttithiumwittrisuspensioi oi I equiv of Cul (eq 6). d Yields obtained on oxidalion with o. a! 0'. If all the oxygen added had dissolvedin the reaction solurion. its equrlalcn!concentration . -78": would have been 1.4,L/. Oxidation wilh 01 at equivalentconcentration 1.4 M, /Oxidation wilh PhNO! at 0"; , equivalent concentration0.67 rll. The reaction was stirred at 25-27' for 2 h. ano *ten treareJiotO-io" ror z tr.

form at comparablerates. Similar data for reactions methyllithiumwith aryl iodidesin the absenceof copper with l-iodonaphthaleneare presentedin Table II; in saltsoften givesyields of coupledproducts comparablc this caseconsumption by the aryl iodideis completein or superiorro those obtainedusing lithium dimethy,l- less than 8 hr. The addition of , cuprate. However, comparison of entries I and l , or di-n-butyl sulfide to solutions ot of rable I establishesthar the presenceof methyilithiur' lithium dimethylcuprare(t) preparedfrom puremethyl- in excessof the stoichiomerryrequired by the formula- copper hasrelatively little efrecton the rateeither of the tion "(CHr),CuLi" does nor appreciablyenhance the metal-halogene,\change reaction or of the coupling reactiviryof the copper are complex in the coupling reacrion. Addition of I equiv of tri-n-burylphosphine reaction. to a reactingsolution of lithiunr dimethylcuprateand A possibleclue to the differencein reactivityof purc iodobenzene has two effects: it increasesthe rate of lithium dimethylcuprareand materialprepared directly metal-halogene,rchange as judged by the yield of tol- from methyllithium and commercial copper iodidc ueneobtained on oxidation,ancl it increasesthe rate of appearsin comparisonof entries2,7,8, and 9 of Tablc tolueneformation prior to oxidation. I. The ether-solublecomplex of di-n-butylsulfide ancl Comparisonof entriesl, 3, 4. and 7 of Table I and copper(l)iodide used in the preparationof pure methyl- sinrilardata in Table II establishesthat the reactionbe- copper(t) (eq 7) is obtained by dissolvingcopper(l ) tween aryl iodides and pure lithium dimethylcuprate. iodide in the sulfide. Commercial "copper iodide" preparedfrom methyllithium and methylcopper(l),is ordinarily containsapproximately 5 ft impuritieswhich appreciably slower than that wirh lithium dimethyl- are insoluble in di-n-butyl sulfide. Entries 8 and 9 cuprate prepared by reaction of methyllithium and summarizeexperiments in which thesedi-n-butyl sulfide copper(l)iodide: the latterreaction appears to be com- insoluble residueswere collectedand added to copper plete in l5-30 min. while the former processrequires ate complexesprepared from pure methylcopper. Sur- 8-2-l hr. Further, although the yield of toluene ob- prisingly, it appearsthat addition of theseresidues ttr tained on oxidation of the latter reactionmixture is the organocoppersolutions significantly enhances their comparableto that obtainedon oxidation o[ reaction reactivity in the nono,ridativecoupling reaction. Work mixtures incorporating pure lithium dimethylcuprate, in progress is designedto explore the significanceot- theyield of tolueneproduced in the directcoupling reac- theseobservations. and anydiscussion of the mechanism tion is significantlylower. Thus. it appearsthat metal- by which the di-n-butylsulfide insoluble residues mighr halogen exchangeis significantl,vmore rapid using the influencethe courseof the couplingreaction is clearly' reagent prepared by reaction of methyllithium and speculation. Nonetheless.these results raise the in- copper(l) iodide rhan using pure lithium dimethylcu- triguing possibility that metals,other than copper, prate. presentin the residuesmay be capableof catalyzingthc The reasonfor the observeddifferences in reactivity couplingreaction.:{ of the organometallicreagents prepared by the proce- dures representedby eq 6 and 7 is not presentlyclear. yielded 86% l-methylnaphthalene. Consequently, the direcr reection with methyllithium appears to bc the merhod of choice for synthcrrc Methyllithium itself reacts readily with iodobenzene mcthylation !3 reactions involving aryl iodides when other function.rl to yield toluene. In fact, the direct reaction of groups in the organic iodide are compatibte with this organometallic reagent. Comparison of these yieids and reacrion times with those in (23) (a) H. Gilman and F. W. Moore, J. Amer. Chem.Soc., 62, lg4j Table I provides chemical evidence that solutions of lithium dimethl,l- (1940); (b) W. Langham,R. Q. Brewsrer,ancl H. Gilman,ibid.,63, S4S cuprate do not contain appreciable concentrations of free methyllithium. (l9,ll). In our hands, reacrionof I equiv of methyllirhiumwith I (24) Nore Apoeo rx PRoor. Semiquantitative flame spectropho- equiv of iodobenzenein ethcr yielded9l f toluenein 30 min at room tometric anal-vsis of a representative sample of the di-n-butyl sulfidc tempcraturc. Under similar reaction conditions, l-iodonaphthalcne insoluble "residue" in commercial copper(I) iodide has established thar

Journul o/'tlrc Americun Chemical srrcierl' I 9l:t7 I August Ij, 1969 TableIII. Reacrionof Lithium DiphenylCuprate with Aryl and Vinyl Halides

(CeHr)rCuLi Organic halide Additiv(s) Reaction (concn. r!/) (concn, ,l/) (concn,M) time, hr Product y,ields, l-lodo- I Phenyl-l,l'-Bi- Iodo- Naph- naph- naph- naph- benzene thalene thalene thalene thyl

0.16 l -lodonaphthalene LiBr (ca.0.48)" I 53 60 ?5 l3 (0 032) ,I 6,i 22 t9 J9 28 0.16 LiBr (ca.0.48)" .t h 525 Oz (excess)" 0.16 LiBr (ca.0.48)," I b 51 ) O: (excess)d 0.16 LiBr (ca.0.48)," A b t0 90 PhNOr (0.40)" 0.16 LiBr (ca.0.48)," ,| 6 :-i 70 MeNOr (0.59f 0.16 LiBr (ca.0.48)," t1 b l5 8l CuClr (0.32Y 0.18 Lrl (ca.0.02) I :5 59 t2 a1 4 .18 ,i6 J JI )) l9 r1 45 I 0.2t LiBr (ca.1.7) bJl J+ 25 (0 042) 35 b5e 2 39

,rrurs-Stilbene 't5 crs-Stilbene 0.2-l I rart s- 13-Bromostyrene LiBr (ca.0.72)" 2.O <2 (0.04e) 4.0 90 'tn <2 0.:0 cis-d-Bromostyrene LiBr (cn.0.60)'

Reaction of lithiunr di-rr-butyl-and di-sec-butyl' for successfulcoupling. Methyl(tri-rr-butylphosphine)- (tri-n-butylphosphine)cuprates:0with iodobenzene copper(l) reacts with l -iodonaphthaleneto give yieldsappreciable quantities of n-butyl-and sec-butyl- l-methylnaphthalene.This reacrion seems to be benzene.respectively, on oxidative coupling, but no accompanied by appreciably less metal-halogen ex- butylbenzeneson nonoxidative hydrolytic work-up change than the correspondingreaction involving (Table I). Apparently metal-halogenexchange can methylcopperate complexes. Unfortunatelythe pres- take placewith thesereagents, but the direct coupling enceof tri-n-butylphosphinein thesereaction mixtures. reactionis slow. and the thermal instabilityof alkylcopper(l)reagenrs Hydrolysisof aliquotsof a reactionmixture contain- other than methyl,severely limit the practicalusefulness ing pure lithium dimethylcuprateand iodonaphthalene of coupling reactions involving the alkyl(tri-n-butyl- demonstratesthat the decrease in the concentra- phosphine)copper([)reagents. tion of iodonaphthaleneis accompaniedby ^ cor- For reaction systems in which metal-halogen ex- responding increase in concentration of both l- change is faster than direct coupling, there may be methylnaphthaleneand naphthalene,the latter com- practical advantagesin certain casesto a coupling pound presumably arising from protonation of a schemeinvolving direct formation of the mixed are l-naphthylorganometallic reagent. The data in Table complexesrequired for oxidativecoupling from organo- II suggestthat nitrobenzeneis a slightly more eftrcient lithium reagents. This schemeis most attractive for reagentfor the oxidative coupling than is molecular couplingsinvolving .rec-or l-alkylcoppercompounds. oxygen. The last three entries in Table II establish The thermal stability of these reagentsis sufficientl,'- that formation of an ate complexis not a prerequisite low that extensivethermal decompositionoccurs under the reaction conditions required for coupling and irs principal mctallic constituents are: Cu (> l0%), Fe (>10%), metal-halogenexchange to take place. In contrast. Na (l-10;), Ni (0.1-1.0'll),and Cr (0.1-1.0T). A mixture of "purc" lirhium dimethylcuprate, prcpilred using the procedure rcpresented bt' both the formationof mixedate complexes by reaction eq 7. and iron( II) chloridc 1<20T, based on coppcr) shorvs lhe same of organolithiumreagents with copper(l)salts (eq 6 and rcactivity'toward iodobenzcnc as material preparcd drrectly from 8), and their subsequento.ridative coupling, can be methrtlithium and commcrcial copper iodide. Nickel(tl) bromide -78o. signiticantly cnhanccs both thc yield and rate of formation of toluene carried out at Thus. for example,sec-butyl- in thc direct coupling reaction ol'"pure" lithium dimcthylcuprate with benzeneis formed in higher yield by oxidation of pre- iodobenzene. Thus, both nickel and iron catalyze the coupling of formed ate complexesthan by directreaction of lithium lithium dimcthylcuprate rvith iodobenzene. Studies of applications and mechanism ot'this catalr-sisarc continuing. di-sec-butylcupratewith iodobenzene(Table I).

l,l,'lritesides,et al. I Litltium Diulk-t'l-und DiarT'lcuprctteReuctions 876

I. 2.; CuBr.T IIF. - ;3. sec-C1H,Li * 4CnH;Li ec-CrHnCrH; soiutions: in most of these reactionswe have ex- -;30 G, (76/"1 amined. the yields of couplcd product obtained after eitheroxidation l. 2.5 Ctrllr,TIII'. - 7go or hydrolysisof the reactionmixturcs t-C.{HJLi * 4CrHrLr --+ l-C{HcCeHi are very similar. Since rhe o.ridationqf lithium di- 2. O:, - 78" (737'1 alkylcupratesgives good yields of dimeric products.rl this observationindicates Reactionof Lithium Diphenylcupratewith Aryl and that thesereaction solutions Viny'l Halides. The reacrion of lithium diphenyl- did not contain significantconcentrations of organo- metalliccompounds cupratewith l-ibdonaphthalene(Table tII) appearsto correspondingto the starting or- ganic follow approximatelythe same pattern that appeared halides.ar the point at which the oxidant was in reactionsof the methyl reagentI with l-iodonaph- added. Although this fact does not by itself exclude the products thaleneand iodobenzene. The operation of metal- of metal-halogenexchange as transitorl. intermediates halogeninterchange in this reactionsystem is unam- in the coupling reaction,the obserr.ej stereochemistry biguousl.vconfirmed by the observationthat hydrorysis oI the reacrionof lithium diphen,v-lcu- prate (-)-(n)-2-bromoburane of a reactionaliquot with D:O after the metal-holog.n with (uide infra) renclers this reactioncourse exchangehas taken placeleads to naphthalenehaving unlikely. Third, couplingsinvolv- ing alkyl halidesare significanrly isotopiccomposition 8074 dr, 20% do, &nd by the si- improved by using a polar nruitaneousappearance of iodobenzeneand naphtharene solventsuch as tetrahydrofuranas the reactlon medium. in aoprorimately equal yields from hydrolysisof ali- Severalspecific points quots taken early in the reaction. Metal-halogenex- concerningthe data in Table IV deserve ch:rngeis completein approximately4 hr at room tem- brief comnrent. First,lithium dimethvlcu- prate (1) prepared pcrrture:the couplingreaction, which may reflecteither front merhyllirhiumand copper(l) direcr rcacrion oI lithium phenyl(l-naphthyl)cuprate iodideappears to hav'ethe samereactivity toward alk,,l halidesas pure *'ith the iodobenzeneformed in the exchange,or does l. Sincethe differencebetw,een the reactivity thr'rntaldecomposition ol a l-naphthylcopperorgano- of these reagentstoward aryl halides seenred nletallicreagent in the presenceof a phenylcoppercom- to be reletedto a diflerencein their activitl,in metal-halogenexchange. pound. continues ntore slowly. Regardlessof the their similarityin a reactron nrechanisnrtrf the thermalcoupling reaction. oxidation system in which metal-halogenexchange apparenrlv does take place crithe mixtureot'orgunonretallic rergents obtained after not is not surprising. Second,it ap- pecrs the inirialmetal-halogen exchange rcuction is complete thet it mav be possiblein certaincoupling reitc- tions rcsultsin efticientconv'ersion of l-naphthylmetalspecies to usc a mixture of ttrganolithiumreagent anti catal.r'ticquantities prcsent in solution to l-phenylnaphthylene.Once of coppcr(l) ittn in place of prc- aglin. nitrobenzcneappears to producethe highest formed diitlkylcupratesto efl'c.ctthe coupling reaction. albeit at appreciable vields of I -phenylnaphthalenein the oxidativecou- detrirncnrto reaction rate anti product yicld. pling: oridationwith oxygeneither rrr 0o or at -78o, The reacrionof threefoldmolar exccss nrtromethane,or copper(ll)chloride gives appreciably of I with rr-octyliodide ttt vicld /r-nonanetakes place lcrw€fyields. quantitativelyin lessthan 3 hr. Reactionof a similar quantity Similarly,reaction of an excessof lithium diphenyl- oI methyllithiumwith rr-octyliodide for l2 hr yields cuDratewith 1,8-diiodonaphthalenein refluxing diethyl only 6% n-nonane. Howcver, addition oi 5 mol copper iodide (based ether solution for extendedperiods of time appearsto I on l-ocryl iodide) to rhe methyllithiunr rcsult in approxinratcly50,|o conversion of the aryl resultsin a 6l''l yield oI rr-nonanein l] Third. iodide to l-phenyl-8-copper(l)naphthalene.as judged hr. lithiumdi-ir-bury'lcuprate reacts with alnlosr b.rthe differencein yield of l-phenyl-and 1.8-diphenyl- equal iacility with rr-penryliodide. bromide,chloridc. naphthalenebefore and afteroxidation. and tosylateto yield /r-nonane.procided that tetrahv- drofuranis usedas Reaction of lithium diphenylcupratcwith c,.r- or solvent. The useof diethylether as results tratt.s'$-bromostyreneresults in high conversionsto crs- solvent in lower yieldsof coupledproducts with n-pentylbromide and trcn.r-stilbenes,respectively; oxidation is not re- andchloride;the use of pentaneas sol- vent appears quired in this reacrionsysrem to obtain high yieldsof to complerelyinhibit the directcoupling coupledproducts. Lessthan 2\ of the stilbeneisomer reaction. Theseobservations are in qualitativeaccorci with the proposition hav'inginverted configuration around the double bond that the responseof the coupling is tormed in each case. For reasonsdiscussed pre- reactionsto changesin solventand leavinggroup are expected viously2sthe observationof retentionof stereochem- those for an Sv2 reaction. Fourth, although rstryin thesecoupling reactions strongly argues against 2-bromobutanecouples in high yield with lithium di- freed-styrvl radicals as reactionintermeciiates. phenylcuprate.the yieldsof coupledproducts obtained Reactionof Lithium Dialkl'l- and Diarylcuprates with on reactionof secondaryalky'l halides with lithium cii- Alkl'l Halides. The reacrionof typical lithium dior- alkvlcupratesare much lower than thoseobtained w'ittr primarv ganocuprateswith atkyl halides(Table IV) differsin halides. The yields of coupled products ob- severalimportant practicalaspects from the reactions tained using t-alkyl halidesare so low that the rc- with ar,vl halides discussedpreviously. First. these action appearsto be of no practicalutility. In con- coupling reoctionsusuallv proceedm()re rapicltyand trast.lithium di-.sec-alkyl-and di-r-alkyl(tri-n-butylphos- in higheryield than do the correspondingcouplings to phine)cuprates:0give good yie ids of coupledproducts on ar.vl moieties. Second, there is no eviclencefor im- reactionwith primary alkyl halides. Thus,coupling ot' portant involvemcnt of metal-halogenexchange in a primary with a sec-alkylgroup is bestaccomplished coupling reactions involving alkyl halides in ether either by reaction of a primary alkyl chloride with a "di-sec-alkylcuprate," (2-s)G. lVI.Whitesides and C. P. Casey,J. Anter.Chem.,Soc., Eg. or by reaction of a primaritl' .t5-lI ( 1966). alkyl bromide with a di-scc-alkyl(tri-n-butylphosphine)-

t Jourrutlol rlte Antt'ricun Chemiculsocier.t' gt;t7 1 August lJ, t969 Table IV. Reactionsof Lithium Dialkyl- and Diarylcuprateswith Alkyl Halides" R-R' yield, /o" Copperreagent. RrCuLi Alkyl halide,R'X LiX Time. Hydrol- Oxida- ysis (concn. rV) (concn,M) (concn,M) hr Solvent tionb - (CH,LCuLi (0.5)" n-CrHrrl(0.1) 025 EtrO l8 l8 05 30 30 35 98 98 (CHr)rCuLi(0.5)'r rr-CsHrrI(0.1) Lir (0.5) 025 56 56 05 75 75 35 98 98 (CH')zCuLi(0.33)d It'CaHrzI(0.1l) Lir (0.5) 2.7 97 ta 64 CH3Li (0.66)* 5 mol 7. CUI' IL (rr-CrHr):CuLi(0.4)' rr-CsHrrl(0.1) I 68 72 2 69 75 26 70 t 98 (rr-CnHc):CuLi(0.4)" rr-CsHrrI(0. I ) I THF 98 2 98 (rr-CrHg)2CuLi(0.4)" rr'CiHrrBr(0.1) I n-CsH': <2 67 2 <2 70 26 <2 (rr-CnHr):CuLi(0.4)" rr-CiHrrBr(0.1) I Et,O 68 72 2 69 75 )6 70

I (rr-CrH,r):CuLi(0.4)" n-CiHrrBr(0.1) I THF 98 98 26 98 (rr-CrH,).rCuLi(0.4)" rr-C;HrrCl(0.1) I EtrO l0 1) 2 9 1) 26 l0 (rr-CrHr):CuLi(0.4)' rr-CiHrrCl(0.1) I THF 80 86 80 86 io 8l (rr-CrH,.,):CuLi(0.4)" rr-CiHrrOTs(0.1) I THF 98 (rr-CrH,):CuLi(0.4)" C'H,;CHBTCH'(0. I ) I THF l2 l2 2 l) l2 26 l2 (r-CrH,).:CuLi (0.4)" C,HiCBr(CHr),(0.1) I THF

lVhitesitles, et al. I Lithium Dialkyl- und Diury'lcuprate Reactions 4878

CTH; CrH' CzH; fortunately,the availabledata are not sumcientlyde- I Ph,PIl.. I ,(--rllrr:Crr Li t tailed to permit a precise HrrrClllOH - -> BrlllGlilH H;iiclllC6Hr(9) description of the bond- DIIII 1 I EIr()-TIIF I forming step. The reaction may involve simply dis- CHr CHl CHr placementof halide at carbon by an alkyl group s (eq l0), or some more comple.\pathway pFoceeding, for [o]tto+10.43-10.69' [o]"o -2l.Ol' [o]'"o+18.70' butaneby treatmentwith triphenylphosphineand bro- ?\_). -I -) CuI + R-CL + I- (t0) mine in dimethyfformamide. This procedureis a modi- R,/ \ ficationof a previouslypublished method:7 which min- imizesracemization by distillingthe bromide from the example,by nucleophilicdisplacement with inversionof reactionmixture as it is formed.2r By analogywith the configuration on the alkyl halide by the copperatom work of SchaefersTand related studiesby Snyder2ewe (eq I I ), followed by collapse of the resultingforrnol assumethis halogenation proceedswith inversion of I configurationto produce bromide of the (-)-R con- R,Cu---\C-l ! fieurationhaving [o]"o -27.01o (neat),corresponding to an optical purity of 76 to 8l[, dependingon the 1,, value acceptedfor the rotation of optically pure 2-bro- R.,Cu(lll)-C\ + --( + RCuu)(r ) mobutane.s0Reaction of this bromide with lithium diphenylcuprate in refluxing ether-tetrahydrofuran copper(l[[)35organometallic compound with retention r7o s6 f ielded( + )-(S)-2-phenylbutaneha','ing [cv]*- * 18.20 of configuration. Until moreinformation concerning to + 18.70"(neat),3r corresponding to 67-68% op- both the stateof aggregationand structureof the coppc.r tically'pure material.3{ Thus the coupling of lithium atecomplexes and the influenceoi alkyl halidestructurc diphen,vlcupratewith 2-bromobutane proceeds with on the rate and stereochenlistryof the couplingreaction predominantinversion of configuration. Comparison are available, further speculation on detailed mech- oi thc optical puritiesof the startingbromide and cou- anismis pointless. plcd product establishesthat thc reacriontakes place Reactionof lithium dialkylcuprateswith ar_r'lhalidcs with 8-l-92T; stereoselectivity,depending on the value diflersfrom reactionwith alkyl halides,in that metal acceptedfor the opticalrotation of the enantiomerically halogenexchange is important. The roleof this nretal- pure2-bromobutane. halogenexchange in nonoxidativecoupling of copper ate complexeswith aryl halidesis presentlyunclear. Discussion Initial generationof an arylcoppercompound and an The experimentaldata presentedin this paper indi- alkyl halide by metal-halogenexchange might be firl- cate that the reaction of' lithium dialkylcuprateswith lowed by nucleophilicdisplacement of halideion t'ronr alky'lhalides proceeds without significant metal-halogen the alkyl halideby the arylmetallicreagent (eq l2). Al- exchange, a mechanism by which requires,in at least . R:CuLi* Arl . - RI * ArRCuLi---> RAr (lll one instance,predominant inversion of configurationat the carbon originally bonded to halogen. Fur- ternatively,the metal-halogenexchange might simpl;' ther. the structureot' the alkyl group bonded to the constitutea side reactioncompeting with direct cou- nretal and to the halogen.the nature of the leaving pling of the components(eq l3). Our data do not group.and the polarityof the solventall exertan in- RI + ArRCuLi=- R:CuLi* Arl -> RAr (tll fluenceon the courseof the reacrionwhich is consistent permit an unambiguousdistinction between these al- with a mechanismfor carbon-carbonbond formation ternativesat present. However,the observationthat which involvesan Sx2 displacementat carbon. Un- dicr_r'lcupratesare capable of nonoxidativecoupling 86.397 (196l). (b) The absolute stercochemistryof 2-butanol has been with aryl iodides establishesthat a mechanismfor cstrblishcd by rclation to lactic acid. Sce K. Wiberg, J. Amer. Chem. carbon-carbonbond formationdoes exist which docs Soc., 74, 3891 (1952), and refcrenccscited therein. (17) (a) J. P. Schaelcr and D, S. Wcinburg, J. Org. Chem..30, 2635 not involvean Sx2 displacementof the type implicated (1965); (b) C. A. Wilcy, R. L. Hershorvitz.B. M. Rein, and B. C. by eq l0 and I l. Chung, J. Amer. Chem. Soc.. 86, 9fl (196.l). point of view of potentialapplication ot' (28) The procedurc used hcrc is similar to that developed in the From the unpublished work of F. R. Jcnsen and V. Krimsley, University of copper"ate" complexesin carbon-carbonbond forming Culilornia at Berkcley. reactions,several practical leatures of this work ilre (19) R. G. Weissand E. I. Srrvder.Chem. Commun.,l358 (1968). (30) (a) P. S. Skcll, R. G. Allen, and G. Helmkamp, J. Amer. Chem. worth emphasizing. First, the most convenientprep- .Soc..82, 'll0 (1960),obscn'ed [a]:so 3t.On" lbr (*)-2-bromobutane and aration of the prerequisiteate complexesfrom a s)'n- calculate that the maximum value should be 39.3': (b) from the data of theticpoint of viewis that involvingreaction of 2 equiv R. L. Letsinger, L. G. N{aury, and R. L. Burrvell,ibid.,73,2373 (1951), a maximum valuc for [a]r,o of 34.3'ma."'be calculated; (c) F. R. Jensen of with I equiv of the ap- and D. D. Davis bclicvc thc maximum value is within the range 33.1- propriate copper(l) halide. This preparationis ap- 3-s.J". Scc D. D. Davis, Ph.D. Dissertarion. University of California plicableto aryl. vinyl. and primaryalkyl reagents.its at Bcrkeley, Aug 1966: (d) P. Salvadori, L. Lardicci, and M. Stagi, Ricerca Sci., 37. 990 ( 1967), shorv that Skell's valucs" ol 39.3o is too successwith secondarvreagents is marginal, and it high. From thcir data a mlximum valuc for [.lr]lio of 35.7o may be fails with tertiary reagents. For coupling reactions calculated; (c) D. G. Coodwin and H. R. [-lucison,J. Chem. Soc.,B, - reagents.lithium di-l-alky'l- ll33 ( I968), obserrcd [a]::o J3.'to tbr ( - )-l-bromobutane and cal- requiring r-alkylcopper(l) culatcd e maxirnunr value ot-3{ 8c. From thcsc rcsults it appears that (tri-n-butylphosphine)copper(l)compounds are th': thc actual valuc lies betrvccn31.4o and 3-s.7o. (l l) Thc absolurc contiguration ot'(*)-(S)-2-phenylbutane has been (15) Cf. A. Lcvitzki and NI. Anbar. Chent. Commun.,40l (l96tl). assigncdby' relrrtion to 2-butanol,r: and by relation to a-phcnylethanol. r3 (J6) Forrnally sirnilar oxidative addition reec! have becrt ttlr- (32) D. J. Cram, J. Amer. Chenr,Soc.,74, :1.19(1952). servcd for a widc variety ol' dt-dt0 transition mctal complexes. Urt' (ll) D. J. Cram, ibid.,74,2137(1951). fortunrtcly' thc s(ereochemistry of thcse reactions is not prescntlv (3.1) J. Kcrry'on,P. W. B. Harrison, and J. R. Shc'ppard,J. Chem. Soc., knorrrr. Cf. l. P. Collman, Accounrs Chem. Res., l, 136 (196E): 658, 661 ( 1926),reportcd [c]::o - l7.l' tbr ( - )-l-phenylbutane. L. Vaska, ibid., l,135 ( 1968).

Journul rtl tlre.^ltrtaricunChcnticul Strciet.t' I 9l:17 I August 13, 1969 4879 only practicalchoice. despite the problemsfrequently Analyses of lithium reagentswere carned out using the Gilman encounteredduring work-up procedures. Second,the double-titration procedure.$ or by titratron wrth a standardsolu- tion of 2-butanolin xylenewith bipyridyI as an indicator.{r high reactivityof methyllithium toward aryl iodides The bis(di-rr-butylsulfide) and the tn-rr-butylphosphinecom- indicatesthat this material. rather than lithium di- plexes of copper(l) iodide were prepared as descrrbedpreviously.ts methylcuprate,is probably the reagentof choice for Copper(l) iodide was purified using a lrteratureprocedure,{t and methylationof aromatic halides. Third, the relative an analogous procedure employ'rng saturated aqueous potassium purify'commercialcopper(l) ratesof coupling and metal-halogenexchange in the bromide was usedto bromide. Solutions o[ pure. halide-freelithium drmethylcupratewere ob- reactionof lithium dialkylcupratesother than methyl tained by dissolvinga suspensronof halide-freemethylcopper in an derivativeswith aryl halidesis such that the yield ot ether solution containing slightly less than I equiv of halide-free unsymmetricaldimer obtainable by direct coupling methyllithium.rs Halide-containingsolutions of lithium dimethyl- reactionappears to be lessthan that obtainablefrom a cuprateswere obtainedeither by'adding a solutionof lithium iodide or lithium bromide in ether to a solution of halide-freelithium combination of metal-halogen exchangefollowed by dimethylcuprate. or by direct reaction ol' 2 equiv of methyllithium oxidative coupling. In certain cases it may prove in ether with a suspensionof I equiv ot'copper(l) iodide in diethyl advantageousto attempt to convert the arylcopper ether at 0". Solutions of lithium dialk_,-lcupratescontaining tri-rr- reagents formed during metal-halogen exchange to butylphosphine (representedin this paper as RrCuLi.PBur) were prepared (typrcatly coupledproducts by addition of a largeexcess of alkyl by adding 2 equiv 8.10 mmol,5.00 ml of 1.62 sT N solution) of methyllithium (as halide-freeor halide-containing halide to the solution. Alternatively,formation of ether solution), vinyllithium, rr-butyl-.sec-butyl-. or t-butyllithium the lithium reagentsof both of the organicgroups to be to I equiv of tetrakisiodo(tri-rr-butylphosphine)copper(l) (typically coupled. followed by oxidative coupling of the ap- 3.18g,8.10 mmol. in 1.5ml of THF or ether)at -78o. Reaction proximatelystatistical mixture of "ate" complexesob- between the organolithium rcagent and thc copper(l) halide was essentially instantaneousunder these conditions. tainedwhen thesereagents are mi.redin solutionwith The resulting solutions ranged in color ltom colorless to pale pink or yellow, and an appropriatecopper salt, nrav providea usefulroute rvere stable indefinitely'at -78''. The thermal stability of these to an unsymmetricaldimer. providedthat this material mixtures varied considerably: lithium di-t-butyl(tri-rr-butylphos- phinetcuprate was the least stable. its decomposition being essen- is easilyseparated from the two symmetricaldimers ' neccssarilyfornred at the sametinre. trallycomplete alter ]0 mrn at 0 ; the analogousmerhyl ate complex shorved the greateststability', display'ing littlc evidenceof thermal decompositionalter 1.5hr at the sametempcraturc. Slightly cloudy solr:tionsol' lithiunr diphenylcuprateranging in ExperimentalSections' concentrarionl'rom 0.16 to ().-i0O/ wcrc preparedby adding 2 equiv of ethereal pheny'llithium to a colcl (0 ) suspensionof purified Preparation of the Organometallic Reagents. All reactions in- copper(l) bromrde. Thesesolutions rangcd in color trom paleyellow volving organornctallicreagents wcre carried out under an inert to a pale greenishyellow with the lcastcolor and turbidirybeing ob- atmosphere of prepurified . Ether and tetrahydrofuran served when thc solutions wcre prcpareri liom purified phenyl- rvcredistilled ltom lithium aluminum hydridc immediately betbre lithium. We rvere consistentlyunable to prcpare thesesolution use.and were translerred under nitrogen using hypodermic syringes by the addition ol' ethcreal phenyllithium solutions to cold (0 to -78") or stainlesssteel cannu[as. suspensionsof purified copper(l) iodide. In all casesa Solutions of methyllithium (prepared from methyl chloride,tin black suspensiorrresulted rather than the solutions obtained wirh ether, r-butyllithium in hexane.sec-butyllithium in hexane.and l- copper(l) bromrde.t3 Solutions ot' lithiurn diphenylcupratecould butyllithium in pentane,obtained ltom the Foote Mineral Corp., also be obtained by the addition ol'2 equiv ol'etherealphenyllithium containedless than0.0l equiv of lithium halide/equivofalkyllithium to an ethereal solution of bistdi-rr-butyl sulfide)copper(l) iodide. reagent. Solutions of methyllithium (prepared from methyl bro- These observations suggcstthat the decomposition observedduring mrde)in ether.obtained from Alfa Inorganics.Inc., were saturated attempts to prepare phenylcopper derivatives ltom suspensionsof wrth lithium bromrde. Solutions oi vinyllithium (THF solution) copper(t) iodide should be attributed to impurities in the iodide which were not removed the purificatronprocessr2 we obtarned from Alfa contained 5 [ by weight. by employed. Halide-lteesolutions of phenyllithium were obtained by the pre- Puritied solutions ol' lithium diphenylcuprate were prepared vrously describedsereaction of iodobenzenewith rr-butyllithium by the general procedure describedpreviouslyts in which the ether- in a benzene-hexanemrxture. The solid phenyllithium was col- insoluble phenylcopper was collected and washed with cold (0') lected. washed with hexane. and redissolved in ether. After the ether under an inert atmosphere. Although the methylcopper ether solution was cooled to -78", the crystallinelithium reagent reagent prepared by an analogous procedure15was essentiallyfree which separatedwas collected. redissolvedin ether, filtered through of halide containing impurities. the correspondingphenylcopper a Celite pad. and stored under nitrogen. Ether solutions of phenyl- reagentcontained l0-20 mol I o[ halide salts. The washedphenyl- lithium containing lithium bromide were prepared from bromoben- copper was redissolvedin an etherealsolution of halide-freephenyl- zene in the usual way. Ethereal solutions of the purified, halide- lithium. tiee phenyllithium were relatively stable when stored in the re- Allylcopper(l) and lithium diallylcuprate were prepared fronr frigerator. For example, an ether solution which was initially 3.05 allyllithium. Following a previously described procedure.{r rl1 rn phenyllithium was found to be 3.00 iVI after 2-months storage 1.955g (6.90 mmol) of tetraallyltinwas allorvedto react with 27.3 at l-2'. mmol of phenyllithium in 29 ml oI ether tor I hr. After centrifu- gation to remove the tetraphenyltin. the supernatantether solution was separatedand found to be 0.97.1,&/ in allyllithium. The addi- (37) The usefulncss of this technique has been demonstrated by tion of I equiv of an ethereal solution ol' allyllithium to a cold Corey and corvorkcrs. 17,lB (-78") ethereaIsolution containing I equiv of the bis(di-n-buty'l (38) All mclting points are corrected and all boiling points are sulfide) complex of copper(l) iodide produced a bright red pre- uncorrected. Unlcss otherwise stated magnesium sulfiatewas employed cipitate of allylcopper. Addition of a second equivalent of allyl- as a drying agenr. The infrarcd spectra were dctermined with a Perkin- lithium converted the mixture to a pale yellorv solution of diallyl- Elmcr, Model 237, grating spectrophotomerer. The ultraviolet spectra cuprate. were dctcrmined with a Cary recording specrrophotometer, Model 14. "Lithium was prepared The nmr spectra were determined at 60 MHz with a Varian Model A-60 di-n-butylcuprate" by reaction of n- spectrometcr. The chemical-shift valucs are expressed either in hertz butyllithium with copper(l) iodide usrng the lollowing proce- or rl (ppm) relativc to a tetramethylsilane internal standard. The mass spcctra rverc obtained with a CEC Model 2l-130 or a Hitachi (Perkin- Elmcr) mass spcctrometer. Analytical glpc analyses were performed on F & iVl !Iodel 810 flame ionization and iVlodel 720 thermal conduc- (40) H. Cilman,F. K. Cartledge,and S. Y. Sim,ibid.,l,8 (1963). tivity instruments. Absolute yields of producrs were calculated from (41) S. C. Watsonand J. F. Eastham,ibid.,9, 165 (1967). peak areas using internal standard techniques, with response factors (42) C. B. Kauffman and L. A. Teter,Inorg. S)'n.,7,9 (1963). obtaincd with authentic samplcs. (43) this decompositionmay resultfrom the prcsenceof tracesof (39) lvt. Schlosser and V. Ladenbcrger, J. Organometal. Chem., E, 193 other transitionmctals in thecopper(l) iodide.rs" (t9 67). (4-l) D. Seyferthand M. A. Weiner,J. Org. Chem.,26,4797(1961).

Llthiresides, et ul. I Lithium Diulkv'l- and Diur"v'lcuprute Reactions dure. Copper(t) iodide t0.677 g. j.5.1 mmol) was placed in a alky'lboraneand then allowed to react with cis-2-butenein diglyme 4o-ml centrifuge tube. The tube was capped wrth a serum 16" stopper. solurronas previouslydescribed. After oxidationof the resultrng and flamed dry under a stream of nitrogen. Ether (20 ml) was trralkylborane. the fraction containing 2-butanol, bp 60- 120 . added to the tube. and the resultingsuspensron was cooled to - 50,. was separated. dried by distillation from calcium lrydride, and then At this temperature 4.0 ml (7.08 mmol) of haride-free rr-butyl- fractronally drstilled in a spinning-band column. The purrlied lithium solution was added. The tube was shaken vigorously (+)-(S)-2-butanol for was obtained in 55T, yield; bp 99_100, (76o 5 min while holding -50 -2O". the temperature between and mm), rr:sD1.3958, d25r 0.800, (neat) - [.r]tto +10.69. (optical punr], ccntrrfugation at 78' separated the resulting suspension into a 79';1.st In a second run where the purification scheme di