: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,