:i /
[Reprintedfrom the Journalof the AmericanChemical Society, 9.1, 8768 ( 19?2).1 Copyright1972 by the AmericanChemical Society and reprintedby permissionof the copyrightowner.
FreeRadical Intermediates in the Reactionof Neophyllithiumwith Oxygen'
Edward J. Panekz and George NI. lVhitesides*
Contribution from the Department of Chemistlt, Massuchu.tetts Institute of Technolugr,, Cambridge, Massachusetts 02139. Receiued Februurv 11. 1972
Abstract: Neophyllithium (l) has beenoxidized in solution by reactionwith molecularoxygen at very low, con- trolled, rates. When autoxidation is carried out at 25" in n-pentaneor n-heptanesolution, a significantfraction of the reaction products contain the benzyldimethylcarbinylmoiety; these products strongly implicate neophyl free radical as an intermediate. [n hydrocarbonsolutions containing tetrahydrofuranor triethylamine,and in pure diethylether solution, formation oIthese productsis largelysuppressed. Neophyllithiumis tetramericin n-pentane at concentrationsof 0.07 M but dimeric in diethyt ether at similar concentrations( -0. l0 M); vapor pressurestudies establishthat I coordinatesstrongly with tetrahydrofuran, but weakly with triethylamineand diethyl ether. Cor- relation of product distributions with the composition of the aggregatesof I inferred from thesephysical studies indicatesthat the unsolvatedtetrameric aggregatesof neophyllithium auto,xidizein major part by a path involving free neophyl radicals, while the solvateddimeric aggregatesautoxidize predominantly by a path not involving free alkyl radicals.
-magnesium Th. reactionof organolithiumand com- tion reactions,{-eas well as those of organometallic I pounds with molecular oxygen is important as a derivatives ol aluminum,r0'r I boron,r0'r2 and other syntheticallyuse-ful method of convertingthese reagents Organometallic Compourrdsrvith Oxygen iltld Pcroxidcs,"translatc'ci to alcoholsand as an almost ubiquitousside reaction by A. G. Davics,Ilitlc Books,Ltd., London, 1969. in their preparationand handling.,r-; Theseautoxida- (4) H. Hock, H. Kropt,and F. Ernst,.'lngew. Chem.,7l,54l (1959)' (5) G. Sosnovskyand J. H. Brown,Chent' Rec.,66,529 (1966). (6) C. W. Porterarrcl C. Steele,J..'lmer. Chem.9oc.,42,2650 (1910). ( l) Supportcdby the NarionalScierrcc Foundatiorr, Grants GP-1.11"17 (7) C. Wallingand S. A. Buckler,ibid.,17,60ll (1955)' and 7266.and by the NarionalInstitutes of Hcalrh,Granr Clt 16010. (8) H. Hock ancjF. Ernst,Chem. 9er.,92,2716,2723,2732 (1959). (2) E. B. HcrshbergFclloiv, 1965-1966: Narionallnstirures of Healrh (9) C. F. Cullis..{. Fish,;rndR. T. Pollard,Proc. Rov. Soc.Ser. '1, PredoctoralFellorv. 1966-1967. 298. 64 0967). (l) )1. S. I(haraschancl O. Rcinmuth,"Grignarcl R!'aclrons of Non- (10) M. D. Carlbinc arrdR. C. W. Norrish,ibid.,296, I (1967); mctallic Substances,"Prcnricc-Hall, Er.rglcrvoocl Clitt\, N. J., 195.1, A, G. Davics,l(. U. Ingold,B. P. Roberts,arrd R.Tudor, J.Chem.Soc., Clraptcr20; T. G. Brikrnirlrrd V. A. Shustunov, Iltrss.Chent. Ret'., B, 698 (1971); A. G. D.tviesin "Orgitnomt'tallicPcroxides," Vol' l, J5.6ll (1966): T. C. Brikirraarrd V. A. Shusrunov."Rcuctiorrs ot' D. Srvcrrr,Erl ., IrrtersciertccNew York, N. Y., 1971,Chaptcr'{. 876
metals.'l8.r0are believedto occur in two distinct. and with alkyllithium tetramers).r; .{, s-'ic:r.e analogt-rus mechanisticallyunrelated steps: first. I equiv of or- to previously proposed mechanlsrs . ; : { u'ould yield ganometalliccompound is convertedto an intermediate a free alkyl radical intermediarc br caibrr:l-mctal metal hydroperoxide by reaction with oxygen; and bond cleavage following electron trans'l'cr ir...:l thc second, this hydroperoxide is reduced to alcohol by aggregrate (eq 6_g). If the oxidized asgr.{:3::' $c:c reactionwith a secondequivalent of the organometallic (RLi), * O: ---> R. + RrLi,' + G reagent. This general scheme has found convincing -> support in the isolation of respectableyields of hydro- R + O: ROO. -* (): ROO. + (RLi)r (ROO)RrLi{+ R. \ + (l) R-M R-O-O-lvl not to fragment before reacting further, hydropcr- R-O-O-M + RM -+ 2ROM (2) oxide salt might be formed without the intermediac." of a free alkyl radical (.q 9-12)." The chain transt'cr peroxidesfrom the autoxidation of alkyllithium and (RLi){* Or + (RLi),.+ Or.- (9r -magnesium reagents under carefully controlled con- * ditions,r-7and by observation that Grignard and or- (RLi){.* * Or --> ROO. * RrLir* (10) ganolithium reagents reduce hydroperoxides to al- ROO. + (RLi)r-> ROO- + (RLi){.+ ill) cohols, and perestersto ethers (inter alia), under re- ROO- + R,,Lio (ROO)R3Lir 02) action conditionssimilar to those encounteredin the autoxidationreactions.{- t I step in this reaction(eq ll) would occur by electron Current interestin the mechanisrnof autoxidation transter. Reasonablestructural precedentsfor thc of organolithiumand -magnesiumcompounds is cen- proposed partially oxidized aggregatesexist. R3Lir* tered about the dctailcd natLlreof the conversionof has beenobserved in massspectrometric studiesre and thesereagents to hvdroperoxiclesalts (eq l). Direct complexesof nrethyl radicalwith lithium halide havc reactionof an organometalliccompound with ground been observedin low-temperaturematrix ir studies.-' state(t:*-) oxygenhas beenconside red unlikely since The essentialdiflercnce between the two pathwaysis the hydroperoxidewould be formed in a high-energy that thc hrst invoivesa freealkyl radicalinternrediatc tripletelectronic configuration, if electronspin angular andthc secondcioes not. momentum is conserved during the reaction.t3 Wc haveexplored the inrportanceof free radicalsas Mechanisticstudics by Russelland coworkers have estab- intermediatesin the autoxidationof organolithiLrnr Iishcdthat the most common pathwayf or the autoxida- compoundsby exanriningthe reactionof oxygenw'ith tion of waukl.y'bu:;ic', rcsonurrcc stabili:e cl carbanionsis neophyllithiLrm(l). Thc'reare a number of reasons a free radicalchain reaction.r't.rr Tlie evidencecon- for choosingncophyllithiunr for study. [t can bc prc- cerningthe intermediacyof freealkyl radicalsin autoxi- paredin high purity,frec ot'lithium halides or alkoxidcs. rr dation of strongl),bu:;ic organolithiurn or -magnesium and it is solublc in hydrocarbonsolvents. Thus. reagentsis less extensive.although the products ob- theautoxidation ot'I can bestudied in purehydrocarbon servedon autoxidationof the Grignard reagentsfrom solutionsas well astni-rturc.r- of hydrocarbonand donor 5-hexenyl bromider;' and a,a-diphenylallylcarbioyltt; solvents. Tiris flexibility in choice of solvent is ot' bromide suggestradical intermediates. A three-step particularimportance in light oi the well-documented radical chain mechanism has been proposedr3- r5 changcin the reactivitvot'alkyllithium solutions that 17:r lor the conversionof organometalliccompoLlnds (as- mav ilccompan)-changcs in thesolvent composition. sumed to be monomeric)to hydroperoxidesalts that The characteristicrearrangcmcnt of the neophylrxtl- is consistentwith these data (eq 3-5). The chain ical to the dimethylbenzylcarbinylradical is a par- ticularly well-understoodprocess.: r'r3 The fact that RM+Or+R'*MO: (3) the l.l-aryl migrationis nor concertedwith formatiorr R. + O:+ ROO (1) of the neophyl radical,and occursonly subsequentttr the formation of a discreteclassical neophyl radical. -+ ROO. + RVt ROOivl+ R. (5) is of particular pertinenceto this work.2{ Neophyl- transferstep (eq 5) could occureither uia electron trans- lithium itself does not rearrangeto benzyldimethyl- ferr 3' t { or displacement.r5 (l7) Orrc-clcctron r>ridution of organolithium rrggregateshas bccrr Two different free radical chain mechanisms for disctrsscclprcviousll' : G. C. Scrcttas arrd J. F. Eastham, J. Arrtt'r. hydroperoxidesalt formation can be written when Cltertr.Soc..88. -<668(196b); w. H. Glazc, C. !I. Sclman, A. L. Blll. Jr., artd L. E. Bray, J. Org. Cherrr..J4. 6-ll ( 1969),and tefcrenccsin cacir. augregatedrather than monomeric covalent organo- (lll) A nunrircr of otrvious !lin.rtlorls ort this schcme could bc pro- metailic compounds are considered(illustrated here posecl . (19) G. E. Hartrvcll arrd T. L. Bro*'rr.Inorg. Chent.,5, l2-(7 (1966): J. Bcrko*'itz, D. A. Bul'us. and T. L. Brow'rr,J. Ph:'s. Chem.,65, l3S() ( I I ) E. Ilillcr nnd T. Topcl, Cltent.9er.,72, 273 (1939J ; S.-O.Lawes- (l96r). sorrand N. C. Y'ang,J.,4ner.Chent. Soc.,8l. -+210 (1959): H. J. Jack- (20)L. Y. Tanlrtcl G. C. Pimcntcl,J.Chem. P/r.r's.,48,5202 (l96ii). obscn.E. H. Larscn.urrd S.-O. Larvessorr,Rei. Trut. Cltin. Pct.vs-Bcts, (21) G. !1 . \!hitcsidcs. E. J. P.rnck. and E. R. Stcdronsky, J. Arttar. 82,191(1961); S.-O. Law'csson, C. Frisctl,D. Z. Dcnny,and D. B. Chent.Soc., 94. lll (1971). Dertny,Tcrrultcdrou, 19. lllg ( 1963). (ll) C. G. Eberhardt nnd W. A. Eluttc,J. Orq. Chenr.,29,2923(196'li, (ll) P. J. l(rusic arrd J. I(. I(ochi. J. .lmer. Chent.Soc., 91. 39.12 F. A. Scttlc, NI. Hlggerty, anci J. F. Errsthitm,J. Amer. Chenr.Soc., iJ6. il 969). 1076 (1964); P. D. Barrlctt,C. V. Gocbci, arrd W. P. Webcr' ibid..9l. (ll) C. A. RLrssell,atal., Adcatr. Chenr. Ser., No. 51, I l2 (1965). 7-125t 1969).und reli'rerrcgsin cach. (14) G. A. Russcll,et ul., lbirl.,No. 75, 171(t968). (lJ) Rcvierrs: R. l(h. Freidlirr.r..1dt'utt. Free-Rudicttl Cltarn', l,2ll t l-st R. C. Lanrb,P. W. Aycrs,Nt. l(. Torrey,anci J. F. Carsr,J. Amer. (196-i): C. \!'1ili1g i1 "l\{olccul;lr Rcrtrrittrgemcrlts'''PartI, P. de i\1rrr6. Cltam.Soc., SlJ.ll(rl t 1966r: C. Walling rrnd A. Ciorlari,ibkt., 92, Ed., Wilo', \cw York, N. Y., 196i. p '107fl': R. I(h' Frcidlinl, \. N. 6609( 1970). Yost, and iVI.Ya. I(horlirra, Rtrss.Chan. Rcc., 31. I (1962)' (16) NL E. Horrtlcn.A..\l.rercker, J. Burdon,und J. D. Rotrcrrs,i6irl., (21) C. Ruchlrclt anci R. Hccht. Cltern.9cr.,98,2160 247I (196-st, 88. 1732(1966): :ec ulso \!'. E, Plrhurn, R. W. Dlrvcrrporr,antj J. I(. C. Ruchilrc]t.ibil..94. :-q99,16()9 rl96l): C. Rtrchardtand S. Eicher, Reirrlrarti,J. Org. L-lrutr.,.j5. :661 (1970). ibid.,95.r9:l (1962)
()-rt Punek, IL'hitestcle.s Reuctittrt ttl 'Yertplt.t'llitliuttt tt'illt qt'rt 8770 ,r''' o.25 Although the rate of reactionof neophyllithiumwith diethyl ether at room temperaturewas sufficientlyrapid yielded / that isothermaldistillation unreliablevalues for the molecular weight, isothermal distillation experi- - t mentscould be carried out at 20o without Significant |l ",/ z competition trom ether cleavage. The degreesof asso- !n 24 :E ciation determinedin this solventat a neophyllithium o () concentrationof ca.0.10// are 2.00and 2.06.26Thus. cl 4x!-Ct2H25OH neophyllithiumis tetramericin n-pentane,but appar- od dcd entlydimeric in diethylether. Other stericallycrowdcd organolithium reagentsare tetrameric or dimeric in hydrocarbon solutions and many organolithium re- agentsform smaller aggregatesin donor solvents.2T The ability of neophyllithiumto form complexeswith donor solventswas determinedby measuringthe vapor composition over pentane solutions of I containing added donor solvent and a small amount of rr-octane o.? o.4 u. o (as an internal glpc standardl.:s Comparison of the partitioningof triethylamineor diethyl ether between THF/ (soturon) a-C8Hts an rr-pentanesolution and the atmosphereover the so- Frgurc l. Vapor prcssrlre-composition data used to examine the Iution indicatedthe presenceof 0.07,A/ I in solutionhad iurcractioubetwcen tctrahydrot'uran ( 1) (TH F) and neoph-"-llithiurn no influenceon the apparentvapor pressureof thes.- rn /r-l)cntanesolr.rtion ilt ambicrlt temperaturc. Data obtaincd irr donors and demonstratedthat any conrplexesformc'd (): thc prcscnceot'-{).07 I are rrrdicatcdlrv those obtained in thc between neophyllithium and these donors must be lrtrscnccol' urganolithiLrrnrcagcnt are irrdicateclby A. Tlre axcs weak. Sirnilarmeasurements made using tetrahydro- rcl)resclrtthc ratitls ill'thc arcasdue to THF and /r-octanc(an rnert glpc standurcl)in glllc traces ot'i.rlirprotstaken frcm the solutiorr furan as the donor clearlydenronstrated the formation c()ntalnilrgI and l'rorrrthe va[)or ovcr thc solutiorr. l-Dodccanol of a complcx of approximatestoichiometry [(RLit,.1' \rl5 a(ldcd to tltc solution to crutuclt thc I at thc irrdicatcdnoirrt. THF]" (Figure l).:c Thus.qualitatively, I coordinates stronglywith tetrahydrofuran.but weakly with dieth;rl etherand triethylamine. cerbinyllith iu nr Lrnder the rr'action conditions en- in FI1'drocarbonSolvents. Reaction t)t' counteredin the autoxidation reactions.:I Finally, Oxidation neophyllithiurnin a hyclrocarbonsolution with oxygcn. the ncophvlradical rearrangenrent is sufhcientlyslowrt lollowed bv hy'drolysis,yields a number of products (k < l0; sec-tat 100')that rearrangementcannot com- whosc relativ'eyields depend primarily on the temper- pctewith reactionstaking placewithin a solventcage.:5 and rate oI addition ot' oxygcn. Rapid addition Thus. observationoI rearrangedproducts in reactions ature oxygen to a solution of I at room temperaturc oi neophyllithiLrmcan be simplyinterpreted in termsof of classicalfree radicals. without concernfor aryl partici- t ''' t-'t (PhC(CHr)rCH:Li,* PhC(CHrh* PhCHTCH(CHr):-r- pation in raclicalformation, or for detailsand 'J timing ot' I ll:() Z 3 thr' processesleading to escapeof the radicalfrom thc phCH,rC(CH,):CH] phCH:C(CH,),: -.:- solvcntcage in whichit isinitially formed. * PhC(CHr)rOH+ .1 56 esults Il I,hCHjC(CHr).:OH+ PhC(CHI):CH:OH * Preparationand Propertiesof Neophy'llithium. Neo- 78 phvllithiumwas preparedby transmetalationof dineo- PhC(CHr):rCH:CH.,C(CH,. ).:Ph + ph,""imercurywith lithium metal and was recrystallized 9 -78o.'rt t'rornrr-pentane solution at Neophyllithium PhC(CH,):CH:C(CH'):CH:[)h* dissolvesreadily in diethyl ether and tetrahydrofuran l0 (THF) but is only solubleto theextent of ca.0.I i/ in rr- PhCHTC(CH')rC(CH r)tCH:Ph pentane. Hydrolysis of representativesamples of re- l1 cry'stallizedmaterial yielded tert-butylbenzenequan- titativelv: neophyl alcohol was detectedin less than results in formation of neophyl alcohol (8) as the only' 0.lT; y'ield. Reaction of 1 with lithium tert-bvtyl oxygen-containing product. Under these conditions. peroride in ether solution at room temperaturegave the availability' oi oxygen in solution is presumably rreophylalcohol in 90% yield. No product derived (16) In onc expcrimcnt ttrc isotlrerrnal distillatiorr apparatus \\its f'rorl the benzyldimethylcarbinylmoiety could be de- opcncd under lr rrirrogcn atnrttsphcrcut'tcr equilittritrm htrd been attarncd tectedin eithcrexperiment. Thus.the neophyllithium antl thc neophyllithium nls qucrrchcd*itlt l,l'eiibrornocthane. GIpc trsedin the autoxidationstudies was free benzyldi- anitlysisirtclicatcd .r 90i yicld ot'ncophll bromrclc. of (17) H. L. Lcrrts urtcl T. L. Brttrrrt. .,/..'1 rrtcr. Cltem. Sac',92. 1664 methvlcarbinyllithiLrnrand of neophyl and benzl,ldi- (1970); P. \\'est. R. Waack, arrd J. I. Pttrttrot.ibitl .,92,8"10 (1970): \\ ' nrethylcarbinyl alkoxides. H. Glazc and C. H. Frecrtran.ibiLl ..91, 7l9S t1969); C. E. Hitrtu'cll -l-{ | t. of aggregatiorr .rrrd A. .-\llcrh.rnd. il:id.. 93. I -s t l()7 The extcnt of neophyllithiumin l- (:S) It. Wllck. \1. A. Dorlttt, lttttl [). E. Stevcrtsott,ibitl.,88, f l()() pentanewas dctt-'rnrinedb-v isothermaldistillation at (1966). room te'r1)pefxture.Trvo deternrinationsof the ap- I l9 ) Plots sinril;rr to that irt Figure I rre re obtlrincd itr cxperinrertt ' carricd out tc tcst thc cxpcrinretttll tcchrricltrcusirrg 0.05 N n-but1 l- parent molccularweight yieldeddegrees of association lithium in 4-petttarrc itttd sther or trrethliamirtc. Thesc plots conti rrrr rrof J.80and 1.9-lat a concentrationof I of ca.0.07N. thc cxistcrrceol'cornplcxcs ot'lpproxilttittc stoichiomctry (rr-BuLi)r'TEA artd (rr-lluLi),:'OEt: inttrrcd fronr.tnltlogous studics usll'lgmore corl- tl5l R. \1. No.r'cs,Progr. Rc,uct.Kirtct.,l,ll0rl96l). ccntnrtcd solutiorrs(scc thc Expcrirncrrt;.tlScctiort).::
Jr)ttt'nttlttl rlte rlnrericutt Cltanricul.Srrc'icr_r' 91:25 I Dec'cntltcr t3, t97l Table I. The Influenceof Oxygen Addirion Rate and Reaction Temp€ralure on Product Yields ( i;) in Oxidation of Neophyllithium'
Solvent n-Pentane rr-Heptane Temp, oC )5 )5 25 25 25 45 70 Oxygen addn rate (ml/hr) 29 5.5 3.I 3.ld 3. lb J. t _ 3.1 Product
) )+.I C6HiC(CHr)r (2) 8.4 12.4 12.2 26.O I 31.6 crHrcH:cH(cHr),(3) 0.5 1.3 0.7 )2"10 0.8 1.5 (4) 0.6 1.5 <0.2 1.0 i t2 l0 CeH'CHzC(CHTFCHT ar CoH,,CH:C(CHr)z (5) 0.t 0.4 <0.I 0.9 02 08 J.+ CoHsC(CHr)2OH (6)" 0.8 0.4 o.7 0.-l 0.8 05 Froduct ba,lance, /o 103.7 91.9 95.9 103.4 99.7 95.2 80.0 lf, reanc,ngement in A1 dimerrc hydrocarbons 5.0 8.6 10.8 4.9 10.s 2l alcohols 10.6 13.8 t7.0 10.I 9.2 13.3 145 Dimerlalcohols o.26 0.24 o.26 o.23 0.28 o.22 0 19 . l0 ml of 0.05 l{ solution of neophyllithium was oxiCizedin the flask diagammed in Figure 2. Yields are basedon organometalliccom" ponent are estimated to be accurale to +l% (relative). t Duplic4te exp€rimenls. The exlen! to which they resembleone another ls and r iypical of rhe reproducibility encounreredin rhis work. . Characterizedby glpc retenlion time only. R .efers to neophyl; R' refers !o benzyldime.hylcarbinyl. relativelyhigh.'r0 Sincethe rate of reactionof simple coor I lory Inlcl luba alkyl radicals with oxygen is close to diffusion con- trolled,'rtl.l-phenyl migrationin any neophylradicals t'ormedunder these conditions would not be expectedto compete with scavengingof the neophyl radicalsby To vocuurn' nlltoga n oxygen. ln order to provide reaction conditions in monrfold which the rearrangementof an intermediateneophyl radicalcould competewith this scavenging,the steady- stateconcentration of oxygen in the solution was re- ducedto a low valueby slowlyintroducing this reagent into a nitrogenatmosphere above a vigorouslystirred solution ol 1 from a capillaryinlet (Figure2). Prod- ucts obtained in representativereactions carried out usingthese conditions are given in Table I. For com- parison,this table also includesproduct distributions Tcf lo n-<,ovarcd rnoqnalrc 3lrrrrnq bor observedat higher oxygenaddition rates.and at higher temperatures. In practice.the reproducibilityof the product yields obtainedin theseexperiments was only fair: variable Figure 2. The flask usedto carr)-oLtt the autoxidationexperltrlcrlt\. lrom a 100-mlKjedahl flask.modrlicti lrr (< l5l) amountsof adventitioushydrolysis (but ttot of This flask wls constructed addition of a capillary inlet tube lbr introduction of oxygen.attcl b,r oxidation) apparentlyaccompanied manipulation of I bevelingthe bottom of the flask.to improve the efficiencyol'strrrrnu during the courseof the experiments.and consequently the absohrreyield data derived from theseoxidations varied. In order to minimize ambiguitiesin inter- although they were not completelyreproducible. thev pretation arising from this uncertainty in the relative did provide a more stable basisfor interpretationthan quantitiesof I consumedby reactionwith oxygenand the raw yields. Nonetheless.the small unexplained by unintendedreaction with water. Table I includes residualvariation in the resultsof theseoxidation rcac- three parametersderived from the product yields: the tions is suffficientthat qualitativetrends in the data ot' "percentage rearrangement" in the dimeric hydro- Tabie I should be consideredmore signifrcantthan 1n carbonsand the aicohols(defined as 100(0.5l0 + 11)i individualdatum flromany oneexperiment. (9 + l0 = l1) and 100(7)t'Q+ 8), respectively,where. Control experimentsin which the lithium salt 9t' c.g., t0 indicatesthe yield of compound 10), and the neopentylalcohol was addedto pentaneSolutions trt' 1 ratio of the vieldsof, dimeric products to alcohols. In prior to autoxidation establishedthat alkoxidesharc principle.each of thesequantities should be indepen- negligibleeffect on the productdistribution. The rati,' dent of snrallvariations in the amoLlntof adventitious of dimers to alcoholsis also unaffectedby changcsirr hydrol.v-sisoccurring during an e,rperiment:in practice, the reactiontemperature and oxygenadditiofl r&tc'' oxidation of 1 in the Presenceof CoordinatingBascs. rl0) The mole fnrctions of ox1'gen sa!uriltL'd cther, rr-hcxarre,and The addition of small amoLrntsof THF, triethylanrinc. rr-hcptarrcur l,<' urc 1.98 X l0-.t, l.9l X [0-1, ltnd 1.97 X l0-r, of 1 causetli.r respcc!iveir': J. C. Cjaldbaek, ,lctq Cltetn. Scurul., 6, 623 (1951). or diethyl ether to pentanesolutions (ll) C. A. Russcil in "Pcroxidc Rclctrort iVlcchrnisms," J. O. Ed- simultaneotlsincrease in the ratio o[ dimersto alccrltol: rrrrrds,Ed.. Irrrcrscicrrcc,Ncw York, N. Y., 1961, p 107; scc i.tlsoP. D. ancla decreasein the percentagerearrangement irr tlre Blrtlctt, R. E. Pincock.J. H. Rolston, w. G. Schirrdclarrcl L. A. Singer, change of thc:c J. ..ltrrcr.Cltatrr. Soc.. t7. 2590 ( 1965). alcohols (Table II) Plots of the pi1l1 Pttnek. LVhire.sitlesi Reuction rtl'NnPht'llithiurn Ov'''11"t Influenceof Added Tetrahydrofuran.Triethylamine. or Diethyl Ether on the Productsof Oxidatronof Neophyllithiumin Product, % (TH Base/CeHsC(CHr)rCHrLit 0.0 0.25 0.50 1.0 ho Monomeric hydrocarbonso 21.2 20.4 31.6 22.s 34.9 C6HlCH2C(CHr)zOH(7) l0.l 5.0 1.8 1.4 0.7 c6H'c(cHJrcHroH (8) 49.3 M.4 34.2 Jt.) 30.1 RR (9)^ t2.4 20.0 22.5 27.8 26.4 RR',(10)i'i 2.5 4.2 4.8 5.1 5.4 R',R',(11;r,'; 0.4 0.6 0.3 0.3 0.4 Product balance, /" 9s9 94.6 95.2 94.4 98.5 /o reanangement in Dimers 1l ll t0 9 l0 Alcohols 17.0 l0.l 5.0 3.6 2.3 Dimers/alcohols o.26 0.50 0.77 0.86 1.05 ' 10 ml of0.05 ly'solution of I was oxidiz€d at room temperatu.ewith an oxygenaddition rate of 3.1 .nl/hr, unlessotherwise noted. t Milli- rnolesof TEA, TH F, or diethyl ether/mmol of I in solution. . 192mmol of ether/mmol of 1 correspondsto a solution of I in ether with no / pentanepresent. Oxygen addition rate I I ml/hr. ' Oxygen addition rate 29 ml/hr. / Oxygen addition rale rapid (>50 mvmin). . No 20.o - €> 16, o o o o 9 r2.o 9 o E o 2 u.o CE a s o o o E E e'o u o o c o > o E u-"--lj-ilil-iJ-.-, n-[ 6 E '.o o.o o.o o.25 o.5O 2.O In,r,otRorro [rxr],2[nul In,r,orRorro [rea]Z[nl'] 'l'he Figure3. influenceof added rH F on the productsobrained on Figure J. The influence of added trrerhy'lamine(TEA) on thc autoxrdation of' neophyllithium in rr-pentanesolution. The trvo products obtarned on autoxidation ol'neophyllithium in n-pentanc vertrcal a,\es represent the per cent rearrangement in the alcohols solution. TItc a.resand initial concentrationsare the sameas tl'rosc and drmerialcohol rario. respectively'(Table It), observed in the in Figure i; the inrtial concentratlonot'I rvas0.05 N in eachexperi- autoxrdatlonas a l'unctionof the initial ratio ot'concentrationsol' ment. added rHF to neophyllithium. The initial concenrrationof l was 0.05/V in eachexperimenr. added sufficientlyrapidly that oxidation was complete product parametersrelative to the initial ratio of in I min, essentiallyno dimeric productswere formed. neophyllithium to T HF (Figure J), triethylamine Thus. the reactionpath leadingto dimerizationis com- (Figure4), and diethylether (Figure 5) show a qualira- pletelysuppressed if the availabilityof oxygenin ether tire correlation with the coordinating ability oI the solution is high. Aliquots removedduring an autoxi- bases(THF dation of I in pure ethersolution at 10,50,and 1009; particular interestis the clearly defined break in these completionall had the sameratio of dimersto alcohols productparameters at an approximatestoichiometry of and contained no rearrangedalcohol. Thus, as in 2 equiv of I to I equivoi THF (Figure 3). This break pentanesolution, alkoxideformed during the reaction correlateswith the previouslydetermined stoichiometry had no apparent influenceon the reactionproducts. of the complexbetween I and THF (Figure l). When Lithium peroxideor sodium superoxidessadded to I is autoxidizedin pure diethyl ether soiution the for- pentaneor diethyl ethersolutions of I wereapparently mation oI rearrangedalcohol is completelysuppressed. unreactivetoward 1. However.these results may not Thus the autoxidationof solvatedI to alcoholsappar- be mechanisticallysignificant since the peroxide and cntly follows a much different pathway than does that superoxidesalts appearedto be insolublein the reac- of unsolvatedl. tion solution. Increasingthe rate of oxygen addition to a pure Discussion ether solution oi I smoothly decreasedthe rario of dimers to alcohols (Table II).r, tf the oxygen was These str"rdiespermit two principal inferencescon- cerning the mechanismsoI autoxidationof neophyl- (31) The pcaksassumed to becompounds l0 ancrll in autoxidations run in cthcr-richsolutious rverc lssigr.red only on the basisof rctelrtion ttrncs,urrd the yieldsrcportcd irr Tablc II tor thesccompounds are thus (33) Sodium rathcr tharrlithium supcroxidervas uscd in theseexperi- unccrllin. Thc i.rpparcnttbrmrtion of rcarnrngcdtlinrers but not of mentssincc lithium supcroridcis urrstablcthcrmllly; sce N.-G. Vart- rclrrr;rrrgerttrlcohtrl is surprisirrg. ncrf'rerg,Proqr. Itrorg. Cltetn.,4. l] I ( l96l). Product, % (rEA) Product.I (EtrO) 0.25 0.50 I .0 2.0 29 48 0.5 1.0 4.0 20 40 192" 192"'d L92',' 192' '') 25..r 4r.+ 28.8 .r3.8 42.4 39 2 30.7 20.4 r7.9 28 5 22.3 .176 55.0 11 t 67 64 7.7 4.6 3.3 2.8 5..1 5.9 1.7 1.9 1.6 <0.1 <0.I <0.1 <0. I 35 5 36.6 47.3 32.8 33.5 37.t 33.0 39.9 .16.-l 30.8 33 5 l-19 l8.9 35.8 95 93 7.0 .1r.6 8.1 ll.3 19.3 9.0 16.6 29 .l 25.0 33 0 :3 .1 l8.9 15.8 <0.2 2.2 1.5 1.9 1.8 t.2 2.0 2.? 2.2 2.4 3.6 .r.2 1.5 2,2 3.0 <0 2 0."r 0.3 <0.2 0.3 <0.2 <0.2 0 3 <0.2 <0 2 <0.2 <0.2 <0.2 <0.2 <0.2 <0 2 79.5 93.2 97.3 91.7 9r.7 100..1 80.6 85.0 lm.8 88.2 946 89.1 95.0 87.7 97 13 12 7 ll 5 5 12 61 6665 8 15.9 14.9 l.l 0 t2.3 9 0 7.0 14.l t2.9 9.2 5.6 .1.6 <0.7 <0 5 <0.3 <0. I 0 28 0 21 0.25 0.28 0.34 0.53 0 30 0.41 0.62 0.87 1.06 l.8r I t2 0.53 <0 1 effor! was made ro determine2, 3, .1. and 5 separatelyin theseexperiments. Cumyl alcohol (6) was presentin lrace amounts (< I 9;) itl ildentttierl cerrain ofrhese etperirnents,but was no! analyzedquantitatively. ^ R refersto neophyl ; R'refers to benzyldimelhylcarbinyl. by glpc retention time only in solutions containing THF and EhO. lithium (1). First, slow autoxidationof 1 in hydro- carbonsolutions proceeds to a largeextent along path- ways requiringa long-livedinternrediate neophyl rad- ical. The detectionof a significantfraction (10-15%) oi products containing the benzyldimethylcarbinyl moietyand thc observationthat the yieldsof theseprod- ucts increaseon decreasingthc oxygen addition rate (in pentane)and increasingthe reactiontemperature (in heptane)are both consistentwith this contr-ntion. Thus. increasingthe reactiontemperature would be ex- pectedto increasethe rate of the 1,2-phenylmigration relativeto other reactionsol the neophylradical, whilc decreasingthe oxygenaddition rate would decreasethe rate of the reacrionof an intermediateneophyl radical with oxygenand increaseits lifetimeand probabilityoi Inrlrol Rolro rearrangement. Second,the neophyl alcohol formed .Elnan,/ ri on autoxidationof t coordinatedwith donor ligands Figure 5. The int'luenceol' drctltvl eilrcr concentration ()rl tlre doeslot havefree neophyl radical as its precursor. The products obtained on aLltoxidtttott ol' ncophl'llithium in rt-l)cnti.r rlu substantialintluence of small amoLrntsof THF on the ctl'lcrsolutlons. Tlte axeshave thc samemeaning as thosein Frgtrre percentageo[ rearrangedalcohol formed on autoxida- 3. The rnitial concentrationot'I rvas0.05 ,V tn eachexperintctrt. tion of I (Figure3) and the generalcorrelation between productdistributions and the strengthof coordination However.despite this uncertaintvconcerning the mcclt- betweenI and the donor componentof the solution anism(s)of conversionof I to dimers,the argr-rrnents indicatethat the solventeffects that provide the basis derivedfrom the distributionsof alcoholsestablish that for this assertionare not due simply to changesin bulk at least two fundamentallydifferent mechanisms exrst propertiesof the solvent,but rather to specificinter- for the autoxidationof thisorganolithium reagent. actionsbetween 1 and the donors. Further, sincethe ExperimentalSection solubilityof oxygen in pentaneand in the donor sol- ventsexamined is similar,s0the lifetime of a neophyl General Nlethods. All reactronstnvoiving organometallic cclnr- atmospheres of prepurified or radicaland the probability of its rearrangementbefore pounds were carried out under Crade A trelium using :tandard techniques.'t5Dioxane was pll- trappingwith 02 should be essentiallythe samein hy- rified b1' distillation under nitrogen I'rom a dark purple solutton ol drocarbonand donor solutions. Finally,ether solvents sodium benzophenone dianion. Etl-rer.tetrahydrofuran. and trt- are not sutTrcientlyactive as hydrogenatom donors to ethyiamine were distilted ltonr lithium altrminum hydride undcr rt suppressaryl migration in neophyl radicalsgenerated nitrogen atmosphere immediatcll' before use. Hydrocarbon s()l- vents were scrubbed rvith concentrated sulfuric acid to renlo\c in reactions.:r';r{ yield other Thus, the decreased of olefinic impurities and distilled from a suspensionof sodium ['renzo- benzyldimethylcarbinolobserved when 1 is autoxidized phenone ketyl under a nitrogen atmosphercimmediately bel'orctrsc. in the presenceof donor solventsis not due to rapid Melting ltoints rvere obtained using a Tltomas-Hoover catrillerr reactionoi neophvl radicalswith oxygen or solvent, melting point apparatus and are uncorrected. Boiling poittts ;.ttc werc rtlll as Carbon tetraChlOridg51rltt- but to a differencein the mechanismsof formation of uncOrrected. Nmr Spectra tions on a Varian A-(10spectrometer; chernicalshifts are t€llortutl alcoholsirom unsoivatedand solvatedl. in parts per milliorr dorvntield l'ronr tetramethylsilaneand coul''ltttg The role of the neophyl radical in the formation of constantsin ltertz. Intiared spectrarvcre taken in sodium c[ltrt'tde dirnerson aLrtoxidationof solvatedI is presentlyr.rn- cellslsing Perki;r-ElmerNlodcls li7. ll7B. or 337graling spectrorrl- clear, sincc rearrangeddimers are apparentlyformed eters. NIass spectra lvere determincd on lt Hitachi Perkin-Elrttcr' N{odel RivlU-6D mass spectropltotometer. Microanal;ses \\crc even in donor soivents,in which free neophyl radical pertormedb1' Nlidwest i\licrolab. Inc.. Indianapolis. Ind. can be excludedas a precursorof neophyl alcohol. (l-1t C. Rucitardt .rnd H. Trautrvcirr, Cltetrt. Ber., 96, 160 ( l96l); (3-r)D. F. Shrivcr,"Tltc r-tartipulationof Air'Scrrsitive'Compotrrr(li,' sccrriso C. Ruchlrdt und Il . Tratrlrvein. ibid..93. ll97 (1961). llcGntrv-Hill Book Co.. Irtc..Ne* \'ork. \. Y.' 1969,Chapter 7. Pttnck, Ll'ltitesiclcs ,t Reuctiort ttl Nartpltyllitliuttt tvillt O.ut'4r'rt Analrtrcal glpc analvscsrvere performed on F .t M gl0 lvlodet cannula under a nitrogen atmosphere to rhc other side of the ap- Insrrumcntscqurpncd wrth llume ionizationdctectors uslngresponse paratus. The apparatus was agein allowed to warm to roorn lactrrrsobtarncd ',vrtirauthcntrc samples. All components in the temperatureand the volume ol'thc organomctallrcsolution measurctj rcactr()nml\rurcs could lrc scparateduslng a srlanrzed6-ft 137,;sE- (1.2-l mlt. The two solutions were dcgasv:d b."-successive freeze 5l on s()-l(){)mcsh Chromosorb w column operating at 150,(l'or thaw cyclesat liquid nitrogen temperature and the second arm was compounds 2 ft) or lJ()' (lbr compounds 9-ll). The monomcric sealedunder vacuum. The solutronswcre allowed to equilibrarc hrdrocarbons could be analyzed more uccuratcry g-l't using an at room temperature; equrlrbriumwas reachedwirhin 3 days. Thc l0', uc-\!'98 .n 80-10()mesh chromosorb w column at ll0'. finalconcentration ol'l rvascalculated to bc 0.07 ,V. .The lrcid ot'tr'r'r-butylbenzcnet'ormed in the oxrdations was cor- Extcnt of .\ggregationof Ncophyltithium in Diethy'l Ether solution. rectcd l'or thc xmount ol' tcrr-butylbenzene present in the stock The apparcnt molecular rvcightof ncrprrvlrithrum in diethyl ether solurron't' l. as dctcrmined by 1.2-dibromoethanequench. com- solution was determrned relative ro I rutt s-9-ra rt-butyl- lO-methy,l- pounds were rdcnrrfied by collection ttom glpc and comparison of 9,1O-dihydroanthraceneat -20' in trremanncr describedabove for ir sprecrratCCl,) wrth thoseof authenticsamples. /l-pentane. To one tube of t.he molecular weight apparatus wcrc conccntrations ot' organolithium reagent solutions were de- added l.-18ml of a 0.0271 M diethyl crhcr solurron of the stan as an internal standard by forced siphon containing /r-pentadecane [ernc.j7[n-But-r] stainless steel cannula inserted through the side arm. through a 0.25 0.5f, Oxygen was supplied to tlte tlisk irom a compressedgas cylinder r/s-in. thrbugh a capillary bleed fashioned of crimped aluminum tubing lastenedto a l215 ball joint with epoxy cement. Since the flo* rate through this capillary was a t'unction oi the pressuredif' accuratelv by lerential across the capillary. it could be controlled o o regulating the pressureon the redr.rcingvalve at the oxygen tank. bxidations of the organometallic solutions were allowed to rt I continue rt a knowrt oxygen addition rate untll an excessof oxygen had been added to the reaction flask. Al'ter the oxidation reaction was complete. the reaction mixture was transterredby cannula to a tube capped with a rubber septum and filled with dry centrifuge o niirogen. The oxidation flask was rinsed with an equal volume of (J ir dry, oxygen-free solvent. the rvash was added to the bulk of the \ o reaction mixture in the centrifuge tube by transfer through the E cannula. the combined solutions were hydrolyzed with 20-30 pl of t! water. and the hydrolyzed solutions were analyzed by glpc. The joints on the oxidation apparatus were lubricated with Apiezon L grease. It was discovered that during the room-tem- perature oxidation reactions much of the greasewas leachedout of the joints by the solvent; however, Apiezon L is unreactivetoward 1. When Dow Corning high-vacuum grease was used in the joints, grease form 2.:l-dimethyl-4- the dissolved reacted with 1 to (E.hcr/rJ4OHrr) r tO4 1361,r1,6ny phenyl-2-silapentan-2-ol. The small amounts ot'THF. TEA. anclether used in the mixed Figure 6. Vapor pressure-composition data used to examinc thc solvent oxidation reactlons were measured volumetrically' using a interaction betweendiethyl ether and neophyllithium (0.05 N rn r- microliter syringe. A l2-ml centrif'uge tube rvhich was capped penrane.A) and r-butyllithium (0.10 N in /r-pentane,tr). Dar:r with a No-Air stopper and which had been t'lame-driedunder a obtarnedin the absenceof an organolithium reagentin pentancarc nitrogen stream rvascharged with 10.0ml ol'a 0.05 N solution of indicated b:- '1. The axes are ratlos ot' the areas due to dicthr i neophytlithium (0.50 mmol) in /r-pcntcne. The donor solvents cthcr and /r-pentanein glpc tracesof'alicluots taken liom the solutron were added irnmediately bct'orethe solution werstranst'errcd to the and liom the vapor ovcr the solution. oxidation ilpparatus. Thc solr"rtionsol' ncophvllithiunr containing thc lithium salt ot' alcohol used in examining the intluenceof lithium alk- neopentyl analrsis ot' hydrolyzed aliquots shorvcd tltlt no reaction had oc- ol' I were preparedbv allorving 10.0ml ol'a oxideson thc oxidation curred rn any case. in rr-pentatre(().50 mmol l) to 0.05 N solution ol'neophyllithium Reaction of the Lithium Salt of Neophl'l Alcohol with Ox1"ucn. (0.25 mmol) ot' neolrenty'lalcohol in I dry l2-ml reactwith 22.0 mg Neophy'lalcohol (1.5-13g, 10.29mmol) dissolvedin ca. 100 ml ot tubc which was capped rvith a No-Air rritrogen-hlledcentrit'ugc ether rvas allorved to react with 6.0 ml ol' 1.7 N ether solution ..rl' were transl'erred to thc oxidation ap' stopper. These solutions methvllithium (10.,1mmol), containingrr-pentadecane as an internui bv glpc as described paratus, oxiclized, hydrol."-zed,and analyzed glpc standard; the resulting lithium alkoxrde was solubl€ at tht: irbove. conccntration. A l0-ml aliquot oI the solution was titrated to .t experimcntscarried to partial Aliquots obtaincd l'rom oxidation phenolphthalein end point with 0.10 rV hydrochloric acid. Thc t'rom the reaction flask by l'orced completion were transfcrred total baseconcentration was 0.12 l/. Oxy'genwas bubbled throtrgh a stainlesssteel cannula into dry 12' siphon under nitrogen through the remainder of the solution at 0'lbr 6 hr. then hydroll'zcd. cerrtrifugetubes. hy'drolyzed.and analy'zed. ml nitrogen-fiiled Clpc analysis ot'aliquots taken bel'oreand after exposure to o,r1'gtn Ncophyllithitrm with Sodium Superoxide r\ttcmpted Rcactions of yielded the same ratio of neophyl alcohol to internal standard. Weighcd amounts of sodium superoxidc and Lithium Peroxide. Reactionof rr-Butyllithium with Oxygen. A 0.05 N ether soltttion (55 mmol) or lithium peroxide ('16 mg, 1.0 mmol) were nrg. 1.0 o[ rr-butyllithiunrcontaining /t-nonancas a glpc internal standltrtl placecl l2-rnl centrifugetubcs. The tube: rverecapped with in dry was allowed to react rvith oxygen in thc beveled-bottom oxidatron anci flushed rvith nitrogen. A solution (10 ml. No-Air stoppcrs apparatus at room temperature rvith rn oxygen addition rate ()l in pentane(0.50 mmol) was added to the 0.05 N) of neophyllithium 3.1 ml/hr. The two major reaction products were butan-l-,rl tubes at room temperaturc: the lithium salts rvere insoluble in (2571and /r-octane( l5 %). this solvent, and no obvious reaction took place. Simrlarly, 5.0' ml aliquots of a 0.05 rV solution ot'neophyllithiumin ether(0.25 Acknorvledgment. We are indebted to Dr. Peter mmol) rvere added to tubes containing 28 mg (0.50 mmol) oi West (Dow Chemical Co.) for advice concerning thc (0.50 peroxide. sodium superoxide or 23 mg mmol) ot lithium estimation of strength of coordination of Lewis bascs The lithium peroxidc appeared to be insoluble.while the sodium l using vapor-pressuremeasurements, and Dr. superoxide appearedto be slightly soluble. The i'otrrheterogeneous to reaction mixtures were stirred at room temperature for "l hr. Glpc JeanneKrieger for assistancein drawingthe figures. Punek, lVltitesiclesf Reaction tl' Neopltr'llirhium witlt O.r;"q'":