. , .t[*p.inted from the Journal of the American Chemical Societ-v-,96, 4937(1gT1).1 Uopyright 1974by the American Chemical Societv and reprinted by permissionof the .opf iight owner.

GenerationanC Utiiization of Copper(I) Ate Complexesfrorn Diastereomericanci EnantiomericAlkylmercury Reagentsl

David E. Bergbreiter2 and George M. Whitesides*

Cotttributiott .frotn thc Dcpot'lrncttt of' Chenti.strl'^Mrissoc.husens Instirrrrc of Teclutttlog.t'.Cambridga. Mu.ssctcimseu.g02 t3A. Recaited F'ebruury ll. l97l

Abstract: Treatmentof alkylmercurichalides in successronwith I eclLrivof iodo(tri-n-birtylphosphine)copper(l) -7E-'in ancl3 eclltivof rcrt-bttlyllithiLrmat letrahytlrofumnrcsLrlts in formarion of , r.,,.riu. atc contprlexwhich incorporatcs thc alk-v-igrourp originalll'Lronclccl to nrercurv. Thc reactionsof this alkyl group rcsenrblcthose of a lithiLrmclialkylcr,rpratc: it can be alkylateclwith alkyl halic'lesancl couplccl with a rcir-bLrt-ylmoiety by oridation with nitrobenzene:it does not. however.Ltncic'rgo coniLrgate aclclitions to rr.iJ-unsaturateclketones. In certain instanccs.btrt not aiways.the overaliconversion fronr alkl'lnrcrcrrrichalitlc 1o product takesplacc with retention of configLrrationat the carbon originally bonclciito ntercur.y..The structure(s)of theseate compleres czrnnotbe establisheclfroni the availabletlata, bLrtclLralitatire eviclcncc sLlggests that lithiurm.copper(l). ancl mercury(ll) are all present in the tnetalcore. Possibleapplications anil linritationsof thesccorn;rlcxe.s in synthesis are brieflyolr- lined.

Th. inversiorrof stereochenristrythat charactcrizcs the specialinstances in rvhichthey have beenprepared, I SN2displacentent at carbonis the basisfor many only onc ol- tric-rdiasterconicrs has bcen obtained.i, important nrethods of controlling stereochemist.yin Indced.crc-n if it ucrc possibleto generatediastereo- organic synthesis(eq 1). In principle, it shoulci bc merically prrrc .rcc'-alkyllithiuntand -magncsium re- possibleto carry out stereoselectivctransfornrations at ngcr-rts,it is not clcar that thcy w,ould be ntorc than carbon usingdiastereomeric carbanions (or their l'unc- marginallysta blc tou ard epirnerization.1-6 tional equivalents)as nuclcophiles(eq 2): tiiescspecics In contrast. diastercorlericallypure or cnriched RL I) rt r) organometallic derivatives of a number of other , tt, R,..V \., metals- particLrlarlyrnercury(II), tin(lV), and lead- - \: l'-f \-('. + :\ r! (lV)--have bcen prcparcdT-eand establishednot to \ _l) R,./' _t\, epirnerizereadily oncc.formed.10 Unfortunately, or- ganornetallic I) derivatiresof thesemetals are only ll,eakly RL t\' R,..-f R''--l n ucleophilicand of Irrlitcd syntheticutility. + )'-X a--v rIl):X The rvork rcportedin this paperu,as directed toward ,CtNIt + rl r ,, ,tt developing R. lL., rnethods for increasingthc nucleophilic

would also be usefulin mechanisticstudies. In prac- (5) F. R. Jcrrscrrand I(. L. Naklntal'c,.1..4trrcr. Chcm..Soc.,88.3437 tice, diffrcultiesin generatingand utilizingthe reqLrired 11966);W, H. Glazc rrnclC. \1. Sclnltn,J. Ore. Chcnr.,33,1987 (1968); W. H. Glaze antl C. i\{. Selrni:n,J. Oruonontatul. Cltutt,,ll. P 3 (1968). nucleophilic specieshav'e preventecicomnton Llseof (61 C. M. \\'hitesiclcslincl J. D. Rotrcrts, J. Antu. Cht,ttt..Soc.,87, proceduresbased on this principic. Gencral ntethods 4878 (lt)65); E.;\. Pcchtolcl,D. G. Ariants, lrnc[G. Fraorkcl, .l. Or.e. (1971): for the synthesisof purediastereomers Chott.,36, 136,S C_'.Frrrcnkcl, C. E. C'rlrrrcll,uncl D. l. Dix, of organorithiunl .1. .ltrtcr. Cht'nt..\or'.,93. 170-1( l97l), anclrcfcrutccs in cach. 1,indl (7) and magnesiumspecies iire not availablc.;r evenin F. R..lcrrsrrrr lrncl B. Ricktrorn, "Elcctrophilic SrrLrstitLrtion of Orglrnorncrcurilrls."McGnrrr-Hill, Ncu York, N. Y., 1968. (l) SLrlllltlrtcc[ _ ill lrart by thc;National Scierrcc Fourtr-lrrtit'rtr,Criutt-s (8) D. S. Nllrttcson,Orltuttontctul. Cltt'ttt. Rr,r'., Sr.c/. .j,4,263 (i969): GP-28586X ancl GP-14247, antl br rhc IntcrnrLrionulCoirr.cr Rcsclrch D. I)oricluncl N{. S. Johnstrn,(hctrt. Cotrttrttrtt.,STl, l37l (1971): G. S. Associ:rtiorr. Ir.ocrrncr,M. l-. Hrrll, lrrrilJ. G. Traylor, .1..lnrar. Cht,m.^9oc.,94, j205 (2) Tcxaco Prccioctoral Fcllou.. 1971 19i'3. (1972): H. G. [iuii ilrr, J. L. Considinc, ancl J. D. Iieurrctl-v,ibirt.,94, (3) H. M. Waltrorskl, yourtg,.1 F. J. intl.listatt),trnrl A. E. . ..1rttcr. 7106(lt)71): O. A. Rcutor, ct al., Zlt. Ors. Khim.,5, l9 (1969)fChem. Clrcnr.soc..86,3183 (19(r4); H. i-. Gocring ancrF. It. \,rccrirron. ibiri.. .-1itsrr.,70.87919b i1969)J. F. R. Jcrrson,J. J. l\,lillcr,S. J. Cristol, aircl 80. ll8; (l()58), ilnrlrelrrelter's irr c.;r.it R. S. Bccklct,.l. Org. C'hertt.,37.:13.+l(l9l:t. ('1) Rcccnt stttclicsof tl.rcn'tcchanisnr of cour,crsiorr of ail<11bronriclr.s (9) G. Ni. \\'hitcsirlcsairci .f. Sitrr Filippo, .1r.,.1..4nter. Chcnt. Soc., to alk,r'inragncsiLrnr -lithiiirrl lnrl rcugcltts bf i..lrctiorr rvitir rrretrriinri i_ 92, 6611(1 970); C'. L. Hill anclC. l\I. \\'hitcsitles,ibirl., 96, 870 (1911). catc thal sl.ccics rcsctnirlittga rutlicll lrl utalrv of its irropcrtics1re r;1cr- ( l0) AlthoLrghlrlk5lnrcrcr-rric rcugcnt\ arc strririctou urclcpinrcrizltiolr ntcclilitcsin thcsc rcactions: <"/.H. \4. wllborskl, lrirrl l\i. S. Arorroll-" r)llcc irrcllltrccl,tlttr rl$ tl crpe ricncc ltncl lr prir,'lttccornrl1trrtication frortr i. Orgurrottrctal. C-hcnr.,5i, 3l il97-l): ti. \4. WlrlborsL). linrl Ni. S. F. lt. Jcnscn l"lrs cnrgrhrsrzecithc possibilitl of thcir cpinrcrization in Aronoll-, (1q73). ibid.,5l . 55 Fi \\'. li. J. IJocieriirz,C. Rlonrbcrg. antl solLttion rlurirrg rccr) stilllizutiorr or chronratogral.rhy. This clrinrerizlL- F. Bickclhaupt, T'ctrthcrlrott,29.7l9 (1S73): R .l Koqcrs. H, L. tlort ilppilrcntlr rcllcets a raclicul chairt rcaction initiatccl by sntall Mitchcll, Y. Fujirvara, a'cl \\/hiresirlcs, C. N,t. .i. Org. tlttlrrt." "lg, E57 arlloLUlts ol irer

t Bar,qbreiter, Il'hituirlt's Coppt'r(l) ,,1te (rtntple,res f'ront Alltt'lntercur1' Reagents 4938 with Scheme I. Organomercury Compounds erdo-l and exo-l Are Converted to a Copper Ate Complex and to Products High Stereoselectivity

+"HgBr endo-l I -78', THF I t. tlcunnur, -78' +| 2. 3(CH1)1CLi,'- rr->\ 3CH3I,-78' 5PhNO2 ------* ALH <- H I ,+"* 7004 - 45% C'Hr c(cHr)r <95% endo'3 [CuLiHg].(C(CH,)r)3 95%endo'4 endo'2 75% exo'3 5/" exo'4 N N /l> 1r-H-T -?Ro 5PhNo2 CH, l\ /'\LcrcH ), rl I [CuLiHg]'(C(CH.),), -40% H -70% H I 12/o endo' ) 5% endo-3 H <95% exo'3. excr2 )98/' ext4 1, lICuPBur,-78', THF 2. 3(cH3)3cli, -78o

HgBr

H exo-l

reactivityof one or more of the classesof organometallic exo-2-norbornylmercuricbromide (1) becauselithium substancescapable of yielding diastereomericallyor alkyl(endo-2-norbornyl)cuprateshad previously been enantiomericallypure compounds,while at the same demonstratedto retain stereochemistryat the carbon- time retaining a useful degreeof configurationalsta- metal bond for long periodssf 1lms.t;r'i'1In a typical bility at the carbon-metal bond. Effort has been con- experiment,a tetrahydrofuransolution containing I centratedon attempts to convert diastereomericand mmol of endo-l was treatedwith I equiv of iodo(tri-n- -78o, enantiomc-ricorganomercury compounds into copper(I) butylphosphine)copper(l)at and then with 3.6 ate complexesI I having reactivityt: and configura- mmol of tert-butyllithium. The nature of the organo- tional stabilityr3'r4similar to that of lithium diorgano- metallicspecies present in the resultingsolution has not cuprates. This effort has been partially successful: beendefined in detail: for conveniencewe will referto certain organomercury reagentshave been converted them simply as e.yo- and endo-Z. The representation with useful stereoselectivityinto copper(l) ate com- usedfor 2 in SchemeI, R[CuLiHg]'(C(CHr),)',should plexes having adequatereactivity for use in synthesis. be taken to refer to the composition of the solution Others, however, epimerize partially or completely rather than to the structureof the complex,although during these transformations,or generateate com- qualitativeevidence suggests that all threemetals are in- plexesof low reactivity. Thesestudies suggest correla- corporated into a common cluster in these ate com- tions betweenstructural features in the starting organo- plexes(uide irtfru). mercury reagentsand the syntheticutility of the derived Addition of rnethyl iodide (3 mmol) to the light copper ate complexes,and provide qualitativeinfor- yellow solutionof endo-Z,reaction of the resultingmix- - mation concerninga new and potentiallyvaluable class ture for 30 min at 78", and conventionalwork-up of copperate complexes. yielded 797(, of 2-methylbornane(3, 95% endo, 5% exo)as determinedby glpc analysis;oxidation of endo-Z Results with an excessof nitrobenzeneat -78' yielded-407i' Initial experimentswere carried out using endo' and of endo-2-tert-butylnorbornane(4, 95% endo, 5fl exo). Theseand parallelresults obtained starting with exo-1 (1966): (11) G. Wittig, Qtrart. Rec.,Chem. Soc.,20, 191 W. Tochtcr- are outlined in SchemcI. Neither the yield nor the nrarln,Attgew'. Chent., Ittt. Ed. Ertgl.,5,35l (1966). (12) J. F. Normant, S.trrtftcsis,63(1972); G. H. Posrrcr,Org. Rcctct., stereochemicalpurity of the productsvaried signilicantly 19, 1 (1972); G. Biihr ancl P. Btrrba irr "Mcthodctr tlcr organischcn with the proportions of reagentsused, providcd that Chcmic," 4th ccl, l3 l, E. MLillcr, Ecl., Gcorg Thicrle Vcrlag, Sttrttgart, is l:1:3. Ii the trans- Germany, 1970,pp 731-161. RHgBr:lCuPEu;:(CHr);CLi (13) G. M. Whitcsiclcs,J. San Filippo, Jr., E. R. Stcclrorrsky,ancl metalation betr/een I and tert-butyllithium is carried C. P. Cascy',J. Anter. Chem. Soc.,91,6542 (1969). out beforeadc ition of ICuPBu3,the productsobtained (1'1) G. M. Whitcsiclesar.rd P. E. I{cndall, J. Org. Chcnt.,37, 3718 t; (1972). from the resultng2 areextensively epimerized.

Journal ol'the American ChenticalSociety I 96:15 I Jull' 21, 1971 4939

Severalqualitative observations concerning solutions chemicalresults obtained with 1. When enantiomer- of 2 indicatethat this solution does not contain either ically enriched (*)-scc-butylmercuric bromide was norbornylmercury(ll) halide, -(tri-n-butylphosphine)- treatedwith ICuPBur and tert-butyllithiumusing con- copper(I),or -lithium in appreciableconcentration, and ditionssimilar to thoseemployed with 1, an ate com- that it also does not contain lithium (tert-butyl)(nor- plex,6, was formed which had reactivitysimilar to that bornyl)cuprate: First, 2 does not react with ketones of 2. under conditionsthat would result in rapid consump- The reactionof enantiomericallyenriched 6 with l- tion of isopropyllithium or 2-norbornylmagnesium iodohexanewas chosen for stereochemicalexamination. bromide. The thermal stability of 2 in THF solution The product of this reaction, 3-methylnonane(7), is (ca.2 hr at 25') is inconsistentwith the thermalinsta- ('H, t ICuPBu" bility of 2-norbornyl(tri-n-butylphosphine)copper(l)and - | 78', Tr-rF also with the reactivityof most secondaryalkyllithium fl>f ('< l('uli}{e l' t('tCt{I i ]{>C<(-,,[{,, The failure of 2 to add to mesityloxide establishesthat t' it is not simply an atecomplex between 2-norbornyl(tri- I C,H, (\,H. n-butylphosphine)copper(l)and tert-butyllithium.ia 6 (+)-7 The simplestinterpretation of all of thesedata is that 2 is a ternary ate complexcontaining copper(l). mercury- stereochemicallystablc under the reaction conditions, (II), and lithium. The number of atoms of eachnretal and also under a rigorotrswork-up proceduredesigned in the cluster(if indeedthere is only one type of cluster to eliminateoptically active impurities (see Experinrental present),the disposition of norbornyl and lerl-butyl Scction). In addition,the absoluteconfigurations of groups on its surface,and the extent to which tri-n- (+)-5rf(,1eand (+)-7:0 are both S,' thus, the stereo- butylphosphineand iodine ion are associatedu'ith the chemistryof the prodr"rctand starting ntatcrialcan be clusterare all unknor.l'n. relateddirectly. Thc stereochentistryobserved during EIl-orts to substitute .sec-butyllithiunr,isopropyl- conversionsof (+)-5 (ca. 3311enantiomeric cxcess) to lithium, n-butyllithium, or phenyllithium for tart- (+)-7 uiq 6is sunrmarizedin TableL butyllithiumin the preparationof 2 w'erenot successl-ul: in no instancewas an ate complexobtained which was capableof transferringthe norbornyl group in either Table I. Conversion of (S)-(*)--3-.v'c-ButylntercurricBrorrridc (5) (S)-(f (7)" alkylations or in oxidative couplings. This observa- to )-3-\1ethy'lnonane tion does not necessarilymean that no ate contplex :l; stereo- was formed on mixing l, ICuPBu3,&fld theseorgano- Reaction Equilibrationr' selectivity' C timc l'or6^ min 5*1 Yield.ll;,d lithium reagents,but only that if an ate complex is !cmn. formed,it reactsby transferof the alkyl group originally - 78, 60 5t 25 -78,,1 bonded to lithium, rather than the norbornyl group. 3(X) 5fi 25 16'17 _78 l0 68 2-5 with high selectivity. -78 60 71 25 The transformationsin SchemeI establishthat it is -lttI 11 l5 75 15 possibleto convert one particular type of secondary were rult with 5 having 32.8'l etlalltlomcrlc organomercurycompound, l, to a reactivecopper(l) ate " These reactions ,; ercess(ee). " E.clLrilibrationtimc represent\the tirne the compler complex, and to induce this ate complex to undergcr 6 rvasallowed tg stir at tlte irtclicatctlrezrction tempcrature. before certain types of reactionsrvith high stercoselectivity. aciclitiol of l-iodohcrane. ' ",, stereoselectivityis delineclas [ee It is not evident,however, that stereochernicalresults (5) - ec (7)liee (5). '1l-hese rcprcsent approxintate isolatecllields glpc work-u;l were obtained using the 2-norbornyl moiety arc necc-ssarill' t-raseclou starting 5. Yields assalecllrr before ca. J-5 -50",;. The r,r,ork-u1-lprtlceclure ttscd rvas specificall," cle- typical of other sccondaryorganic groLlps. The .scc- signerl t9 elirlinate lrossiblecotltanrination with optically active ' butyl group lacksthc structuralpeculiarities associated irnpr-rrities.rather thart to olttintize riclds. The speciallycon- with the 2-norbornyl moiety. and scc-butylmercuric structeclapparatls describeclirl the Erperinrental Section was uot bromide (5) has beenresolved:r' r1' thus. the-scr'-btrtyl uscclin this exlrcrimetrt. As a consccluellce.aclditiorr of lcrl-br-rt1l- reaction nrixture resLtlteclin at lcast a 20-10 c\o- analogof 2 seemedto providea compounclthat u'ould litltium to llre therm. J This reaction \\'asrull in the presellccof 5 eclLrivof aclded give some indication of the generalityof thc stereo- H i\4I)A.

(15) This cpimcrization may rcflcct fornration of l-rrorborrryllithiurr. sec-BLrtyllithiumappcars to invcrt rapiclly on a chcniical tinrc scalc: D. Y. Crrrtin and W. J. l(ochi, Jr., J. ..lntcr. Chcnt..Soc.,84. 1967 The stereosclectir,ityof the overallconversion of 5 to ( I 962). 7 is lorverthan that of thc correspondingreactions of (16) A sinrilar cll'cct is obscrvccl irr rcactions of lithitrnr 2-r.rorbornl-l- ate complex2.2r The loss (irlkyl)cutrratcs: onll u hcn irlkl'l lcrr-butyl clo thcsc conrplcxcs the analogous2-norbornyl transfer 2-norbornll in con.jugatc aclilitions to n.rcsitll oxitlc. I1 It may' bc possiblc to colr\,crt cltltcr rncrcur:(ll) alkyls to rcitctiVrrilte cont- (20) E. LcColi'. S. E. Llrich, antl D. B' Dcnncy, /. ,'lmer. Chcm. plcrcs usirrgorganoijthitrrl tlcrivirtivcsothcr tlran tcrl-[ruti.l. t/ Soc..80.621 ( 1958i. ( l7) The rclativc rcactiviticsof alkl l groups in nrirctl lithitrrl clialk-vl- (ll ) f Ie cxrclt 6f rcteltiotr of cclrtliggrutiotl rcllortccl i1 Tablc I : I his rcllOrtctl clll)ratcs, RR'CuLi, urc rliflicult to 1-.1..''.11.,:r'f. W. H. Mlrnticvillc ltrrtl rct)l'L'sctitsu trtit.tittrttttrvltlltc. JcrlsCt'thiIS Statc(l thitt :r:'1r-r<.t Is probably C. M. Whitcsidcs,,1. Org. Chcnt.,39,400 (1971). rirluc of Irr,] tor tr-(+)-scc-btrtyltllcrcttric trror.rlidc (18) F. R. Jcrtscn,I"-. D. \\'hipplc, D. h. \rVcclcgacrtncr,artd J. A. is slighrly lorv. Buscri on cLlrrcnt cstimatcs ttf tl.rcrotlttioll of'ollticall-v- LarrclgrcLrc,J. Atttcr. Chun. Soc., 82, 14(16( 1960). lrronrrclci:,lrnrl thc assurlption that [rrttmirratitlntlf 5 irt lturc.sc<.-but1l \ (19) J. A. Lanclgrcbc ancl R. D. N{athis, J. .,1rncr.(hcnr..Soc., 88, it-r'rittinctltkcs placc stcrcospccilicalllu ith rctclltion of corrligtrratiotr,; 3545 ( I 966). thc rotatiotr of opticalll pgrc 5 cal bc cstirlratccl to bc irl thc r;.lrtgc

Bergbreiter, White,sidesI Copper(l) Ate C

SchemeII. 'fake Reactionsof Ate ConrplexesDeriveclfrom trutr,t-8 Placc ri'ith High Stereoselectivitv:Proclucts Derivecl fronr cis-8 Are Exlensivell, Eltinrerizecl

CH3

TIgBr trans-$ I I l. lICuP(Bu). : 3(CH?)1CLi +| 5 o-nitrotoluene, -78o 3CTI"I

Crt'Hr ,1811 QRq', imnc 98y' tlans

CH" CH.

3Ct{lI

45"1 C'ulilIgl.it('l i. r,t' r, c(cH3)r CH, 29%cis I :]87icis

I IICuP(Bu), I l, | 2. 3(CH1)'CLi l CH. t" \..

\--]t-a \ Ltt*t,,.

\ i; r l.s-8

in stercochcmistryapparently cloes not rel'iectrucenrizit- sclcctir.ityis obrscrrccl in rr'actions ot-the lattcr, procructs tion of thc .rcc'-bLrtylnrc-rictics o1' 6. sirrcetlie opticul clcrirccl l-ronr thc l'orrncr arc extcnsir e Iv cpirnerizcd pLrrity of 7 appearsto bc indcpenclcrrtof thc lengthot' (Schcrnc ll). Inclistirrguishablcstcrcocher-nicar rcsr,rlts tinre -78'bc'ftrrc that 6 is,llowcclto stundat alkr'llr- \\ r-rc ()btirinccl\\ hcn s()lutirinsof thc. rcagents lrt roonr tion uith l-iodolrcranc.Ruccnrizatiorr night thus bc tcrlpcnrtirre \\ cre lrrlcleclto coltl fcaction nrirtrrrcsand occurring eithcrcluring conre.rsion ol- s to 6. or clrrr.inq rr,hcn thr: feusctltr \\ crc cilr,:fully prccoolcd to - 7g. reaction ol'6. bcforc nririrrg. Thc obscr\irti()n that thc sanre stL-rcr)- ln an ell'ortto clctcrnrinelihat'uuriables lcud to this sclectirit,r, chunrctcrizcs \ cr\ clill'crcnt rcitctions low'cr stercoselectiritf ,rrcl alsr'rto crurriirc anothcr n uclcophilic rttilck ()n nlcthyl iocliclc and oxidatir,c type ol- sccondarvalkt,lnrcrcury reagent lrs stlrrtin_s corrpling incltrcccll.'1' o-nitrtltolucnc sLlggcststhat thc muterial.\\,e cxarlined thc atc conrplcrcsgcncratccl cpintcrization thlrt ()ccurs clurin_qconrcrsit-ln ilf c,i.s-9ttt fronr c'is- and rrun.s-{.-t't'rcth1'lcvcloherylnrcrcuricbro- procluctsr.locs n()t lllkc placc cluring rcaction of thc ulc nride (cis- and trurt.s-8).-'''This substratcoll-crs thc cx- cc-rnrplc.r.hrrt rutlrcr tlrrring its fr)nrirtion. A sarnplcol- perinrentaludr,antagc orcr 5 ')6'',; ()8 that the cliastcreorrreric9 prr-pttrcrll'rrrnt lrrttts-8f iclclccl ",, 11.4r;s-l .J- contpositit-rnol' proclucts clcrirccl l'rorn it cillt hc irs- tlirr'rcth_rlcr cltrh.)..1n.'.rl'tcr sl.ilnding lirr I hi- rrt lN : saycdby glpc. \\itho,t thc - (r. exhaustir.epLrrific'utictn re ircncc.as \\ rih thcrc is ntr indicutionthat thc etrirne r.- qurred for opticalrotatittn mcasrlrclnents. izutit-rnohrscrr.'rl ri ith 9 takcs placc aticr its i'()rnri.rti()n. Experinrents()lt sunrplcshighll cnricheclirr cithr:r Thus. thc nraforiti o1'thc cpinrcrizationrrr' r i r-8. lrncl ('r.r- or r/cir.s'-8cstablisirccl tlrat altlroush hiuh stcrct.r- probahrlvof'6. rrrr-t trrkcplacc clurin_q thc l-r''rnlrli()p\)r ' -l 'Trrl.le thcsc rr'l-qcnts. ln Ilict, cxpcrinrcnts [o] tt l-5.t) ll.t) (r./. Err].t.1-ilrelti1l Secti()p). fic r .rirrcsi6 I orrtlinedin Tublc rrerc c:ilcttllttctl ott titt:lrssLllnntion lirlit tlre lLrt.rliorrtrt'riptre;lil) l-.Lrt.t 5 II susgcst that t i s'-8rnay rcact in a clillercnt nrirnncr ir :n r ]-s.S -1. ,rr frij tr' Et()t{ ). rrrtl tlrlt lirr oIti;rrilr i.urc 7 i, [,.] tlrirn rrort.s-8: spccificall"'.tnrnsnrctlilation + 9.1 (ncltt).r'r of- eithcr Tlrcseelrlcrrlltiorrs lssurrrccl thtrt r,,nlLrrfionrctrc l.rrrrt,. is lilrcrrrllre lirtctl to o1.r1ig'11purit1.,,l .i.r- .r trurrs-8hclirrc ,clciiti.n of-IC,r)(B,),; gircs 1rr.d- (ll) ()1. Rc{crerrec 7, p tucts ii ith stcrL.()clr.nristrl'similar trr thosc rrl- r,i.r-8 {l-i1 6;. \1. r\lrircsitles,\\'. F. Fischcr_Jr...T. Sii ir [:iii111.1;,.Jr..R. \\'. irr SchcnreIl. []rr:lre,rutcl l{. O. Houre,./. .lrtrcr.('lrctrt..!or'..91. -iS7i This trbscrration suggcststhirt in thc '[ 11t;1,r,. (l-+) R. L. l-rrtsjngirunrl .l. (i. rtrlnltltnt,.l . ..1trtt,r.( lrorr..!ac.. 7]. caseof' r'i.v-8l'rcc lithirrrn rcugcnt or s()nreothcr organo- s-l(.)(19-s0). otlrcl lou!r' \.rluL\ i,rp i1,,'\lru.ilre lril,riioir ,rf'l-nrctlirl- nrctallic snr'cicsclrpu blc o1'cpinrr.rizution cxists cluring I)()llutc hiri e l.ecrr reportc(|.1, l{rtrrcycr, tlrc higlrer r iLlrrcrrf p (,).3 [,,],, tlic firrnuriirtrrol-thc contplcr scelllslll()\t rLccr.riirte.:incc thc svrrthcsisgiving tlris r lrlLrcclr(l lr()t 6. irrroit c lrrtr'1911g1j1111itI ilrr .rrr nrrrrutric..errtr,l.. Other l'otcnti:rl Applications of Organomcrcurl -De- (15) F,r a.rc i'rstlrrrccirr *lrich this i;1q,r,tl. lrssiir.rrl-rli.rris r./..\. ril'ecl'\te c'omplcres. Thc stcrcochcnricalcrncrirncnts [-forerrrr.'l'ct rultcrlrort I.ctt,, 3l ] I ( i9(r9). (l(r) F. R. Jen-gr lrnrl L. FI. ( jrrlc, .L .Arnar.Chcttt. .\r11-..g?. : i< alrlirclvorrtlirrctl irrdicatc tlrat thc degrcc or-succcss r.i'itlr ( 1960). w'hich rliustcrrr-rrncriccoppcr(l) atc ct'rnrplcrcscAn trc.

Jotrrrnl tl tltc ,lntericcut Clrcnricul Socit,tt. 96;1.1 .ltiir. lj. lg7-/ 4941 Table II. Reactionsof Atc Cornltleres preparecl frorr figuration. Although the stereochenristry of this re- J- \1cth1lc1 clohex.r lnrercuric Halicles actiolt shoulcl not be takcn too serioLlslysincc thc l)rrtrllrcts . analogouscis diastcrr^ontcr\\ as not availablefor study. Sterco- l'ronr CH,,l - -l}or-n lrlrNC)r, thc proceclure appeurs to of'ler a rnethocl of generating chcrnistrrcll Stcrcochcnt Ster.cochenr ,',, thc f'Lrnctit'rnaleqLrilalent ol' an *-hydroxy tl ( ",, tratt:) Yickl. ",, (",, trerrrs) Yield. (",, tr.irn:) carbaniori. Attenrpts to carry oLrta similar transf.orrlutionstarting 96 +8 gii 77 98 u'ith trott.r-l-rnethoxycyclohexyl-2-nrcrcuric brorlicle 51 72 t) 7l tailcd. presurnably because ol elirnination t; -i-i 12 .t6 7l yielding 96,, ,)-j 7(l cyclohexcnc. Othcr ()xylncrcLrration prod ucts will 16,, -j8 70 serve as sLrbstratcsin this reacti,on. brut thc yielcl o1- alkylatecl proclrrct " trlt-Ilirt-rllithiirrrr *irs atltletlbel'urc l(',.r is qrritc sr.nsiti\c to experinrental I)Btr,rin this irrstuncc. i" ln allothcr:. l('r"rl'llLr,, ria; rrrklecibcl'orc /a./-bLrt\ llithiLrrn. conditi(rns ancl to thc substratc uscd. For c-xanrple. the atc coniplcx f'ronr cr) thro- or iltrt,o-3-hydroxy-2- butylnrercuric broniicle gires no lrlkylatccl product on sencratecj front thc analttgc-rus alkylmcrcrlrv reagents treatntcnt ri'ith ioclorriethalre. u,hile thut l-ronr 2-hy- clc-pcndsupon the strtrcturcof the-alky'i group inr crlrccl droxl'oct,"lnrcrcuricbronriclc yiclrls 5-undccanolin I I ,,,, in a w'av that is not prcscrrtly'cntirclv unclr-rstoocr. In l,ielclon trcatntcnt u ith ittclrrprr)pllnc. far orablc casL-s.thc gcncration ancl utilizatiorr of thc Ary lnrercurilrlsrlt) nt)t rcact in thc sanrc nranncr iis fltncticlnal cq trir. a lcnt of' rliastcrcorncric r)r c-nzurtirrrneric alkl'lnrcrcurilrls. For cxanrplc. the conrpler forrrcd by carbernionsnray hirre practical applicatiorrirr sr nthctic phenylnrcrcLrric brornide. lcLr[)Bu,r. iurcl lcr.l-bLrt'r'l- or nrcclranisticsttrclies. er crr il-acconrpaniecl br, a certain Iithiurn docs l'trrnt /cr'1-butrlbcrzcl.lc il' oriclized r,iith anroLrltto1' cpinrcrizatiolr. Rcgarcllcss o1-stcr!-()chcnricaI nitrobcnzc-nc* ithin l5 rnin ul'tcr nrixing thc conr- outcr'rrrrc.li nrc-thoclof irrcrcasing thc rcacti\ itv of pt'rncnts. Tlii: cornplcr clocs not reuct $ ith alkVl or-qanolllcrcllr)'re agcnts by ate ctlnrplcr fttrntatittn halidcsto tornr rikl I bcnzencs. Af'ter i5 nrin at - 7i rrrightbc uscful in sy'nthesis. the conrpler bcctrnrcsrlrrite urrrcactir c. both chernically We have exantineclbricl)i thc bcharior ol'rcprcscnta- irndthcnrririil. tir.e organonrcrcury rcagcnts that can bc clbtaincclcon- [)rinrar;' orqilnorlcrcury conrp()Lrnclscarr bc rc-acliri,' rcnicntly by procedurcsthat clo ntrt rcquire intelnrerliatc ;rrcparccl f'ronr olcfins ria lr1rlroboriititrn nrcrcuraticln. organonragnesiunror -lithirinr rcilgcltts. r'i:.. nrcrcurir- Thcsc prinrarl ()rganonrercrrr)'reugcnts rcact rapiclly tion. -i oxynrcrctrnltiorr lrncl rncrcLlrvbtrrolr intur- to l'ornt coppcr(l) utc r' cc'rrlpicxes. Thc iilkS,l sroup chitnge. The l-orrnationarrd rcitclitrn rrl'th., lrlc cor.n- originalil bouncl to mcrcLrr-\is trsualll,lranslcrrecl in plexes trscdin tlrcsecxpcrir))e nts \\ ere c.rlri..tl trut u5ing. goocl ficlcl (50 60'1,,b)'glpc.-10 -l0l;, isokirecl)to arr proccclurcssiniilar tr) lhose ulrcadl clcscribccl:a TFIF alkrl haliclc. Thc atc conrplcx ll'ont cthvl i i-(bronto- solution of thc- orgi.rnonrercrrric hllidc \f as trcutcd ut rncrcuri,1rnrclecl noiltt-' rlid rrot. hou er cr. rcact u ith -78' uitir I or nrorccquil ol-ICLrPBu,,. arrrlthen riitlr u rncth,r'l iodidc: tlrc eth-yl unc'lcciinoatcrccor erc-ciorr screral-fblcl cxcess of 1cl'r-butyllithiunr : thc precisc w ork-u1-r ol- thc rcactioir rlixtirre nrily rcstrlt fl'onr conditions chosen clcpc-ncled upon thc prescnce ()r cnolizatiorrol- thc cstcl'f'rrnctictnulitt . irbsenc.'of other l'Lrnctictnalgrclups (r,..g..OH) in tltc Takcn togcthcr. thcsc cxpcrirrcnts indicatc that atc nrolccuIr-thlrt coulcl consur"neor_qaironrctaIIic rc-lrgcnts. cttntplcr itrrituttic'11gr;lrqitlcs ii 1-rossiblenrcthod of- in- Tlic-rcsulting solution ol'atc corrr;rlcr\\as allouccl to crcitsingthc rcuctiriir tri-anrinlbcr of lrnrcltctirct)rg11111;- stir l-or l5 nrin at -78'. ancl uus trcatctl nith thc in- r11ercrlr\ c()ntpoulttlslrr liiilrblc bV ttryr.ncrcrrrationllnd L Il{{O \r') hydroborilii'rii prt,ettlLtres.urttl thLrs rcpclcrs t6csc I I() It classcsol' rnatcriuls rrscf'ulas reugcnts in ccrtain tvpcs lll ol' organic s-vn thcses.

i 2i('L:PI3rr, t'II Conclusions 2 il ('ll . ) ('l.i .Y fyltsir' II lleactirlt ol- alkt lnicrcuric V",,ti 'r. h;illdc-sri ith /r,r.1-hlit'.,1. Cil ,l t )ti lithiLrm in thc prcseltcco1- a solrrblc coppt_.r(l)hirii,i.. 1r'rlri,s-10 r\, -r- li:ii ii;. r1,'1,1., li'iilts gclleratr-SLut ltt{.'ct-rntplex that appcaIS tt) inctrrpt;r-;rt,,, Ii:('ll.l., iiilit iill thrcc nrctlrllicclcnrents. Tlie rcuctiritr rrr'tirc ali.:r,i group originitlll dicirtcclrcilgcnt. c-on1g;5i1'.,n o'l t.rtrrs-l-hvtlroryc\ clo- bondcd to lncrcrir). nr;ry bc signil- ieantlr licxvl-l-nrcrcLrricbrrl'ricle into lr reuctit. ....rpp.i(Il ate cnhunccrlby'this cor,'ri.lexftrrnrutitrn. to u icrcl corrrplcrulrcl subsc-qucntulkvlation ol' this nriitcrial onlv slightlv lcss thiirr rhi,i ch:rrlrcterizing!ithirrnt cli- ali'i'icr-rprurtcs: takc placc in satisfactorlr'iclcl. Thc or crail trans- thcsc lnlrtcriulsrciict ir ith alkr,'lIralides r.tnciu fclrrratic'lt occLtrsl'n ith conrpletc rctcnti()n ol' Lr()n- ith t,.ritlizineagcnts: thcv citt not rcuct u ith .r.rJ- iu-tslrtur;.rtccl kctttncs rrittlcl' c:rtncittions\\ c ltlr',-, cx- rtnrirrccl. ln ccrtuin irrsturtr-'i-S(.,..g., 1.5. trurt.s-8"trtiiis- l0). thcse rcuctit'ursoccur ri jih uscl-Lrlstcrcrrsclie ttr itr : in otltcrs. rcuction rcsults in cg-rirncrizcdproclrrt i. T'hc nuturc tll' thc f'actors rcsprtnsiblei-ol' tire r\- tctlsirc cpintcriziitit-ritoLrscr\ cri ()n rclrctittnsrri'liit. r'()ll* plcrcs clc.rircri 1'ront r i l-8. tlrc tc-rlcnrblcriic.'rt.ii,,.lti;()i.l -[ {ltl) ilc \!li!c 'l t]rf oi- rtiLrir oi'litititrrrr lllii.ttritlcirt rire i-r. lrart.s-l{}cilU\f\ tltr' ,rlt. ,,r;11g.ii'r.iirl-111.1ri11,1 trt iltil grrllti,lL:tt, C. Bi'ou n, ./ e lir'et ts l.ftrtrt'ilrL.lt t,-i:rielr li.) lite ,-lecfC.trci.lt-ullctir itr (ri lithirrrrrrlitlrSlrrr're lrl\rilte s tit.it i96l.rirr lilkorl gl.r)Lli)\.r./. re i lr

(-ttJtlti't'(!l.1tt'('ttti:plc.t't'.slrttrir;1 ll,y/rrit,rctn'r llaugent,s 4942 occuring with those obtained from 6, and the essen- Optical rotations were measured with a Perkin-Elmer Model l4l tially complete stereospecificitycharacterizing reaction polarimeter in l-dm cells. Tetrakis[iodo(tri-rr-butylphosphine)- copper(l)l was prepared by a published procedure.33 c.ro-Bicyclo- of complexesobtained from I are not evidentfrom the [2.2.I ]heptyl-2-mercuricbromide (c,ro-l) had mp 169.5-l 70.0' (lit.o availabledata. The observationthat the stereochemical nrp 169.0-169.5")r enclo-|| had mp l2O 121' (lit.s mp 120.5- outcome of these reactions is not a thermodynamic 121.5'). mixture and is independent of the time between the Resolution of (S)-(-l-)-,icr'-ButylmercuricBromide (5). Using the procedure Mathis,le (-f)-.rcc-butylmercuric preparationand utilization of the reagentsestablishes of Landgrebe and bromide was resolvedas the niandelicacid salt. In our hands.two that the ate complexes are configurationally stable. or threc recrystallizations of the (*)-sec-bLrtylmercuric (+)- The observationthat the same stereochemicaloutcome mandelatc from absolute ethanol at 0o were sufficientto give (S)- characterizesthe two very different types of reactions (*)-^sec-butylmercuric bromide of c'a. 30[ optical purity after 1'35 studied most carefully during this work nucleophilic work-up.3 t r u ns -4-Nlethylcyclohexyl-1 -mercuric bromide (t ru us-8), obtained and oxidativecoupling-strongly suggeststhat the loss by the procedureof Jensenand Gale,26had mp 156.5 157.5"(lit.zn of stereochemistryobserved in reactionof certainof the mp 157.7-1-58');ir (KBr pellet)1449 (s), 1379(s), 1302(m), 1169 ate complexesis not relatedto the coupling reactions (s). 1060(m). 1005(m). 961(m). 908 (m)cm '. The diastereomeric themselves. Thus, it appearsthat the loss in stereo- purity of this material was assayedby converting it to 4-methyl-l- l'ollowed by glpc analysis. In a typical ex- occursduring formation of the ate complexes. bromocyclohexane.sn chemistry periment. r'a. 0.-l g (cu. I mmol) of 8 was dissolved in l0 ml of Metal-halogen exchange reactions are believed to p1'ridine.A solution ot.bromine (0.5 ml) in pyridine (10 ml) was involve free radicals,at least in part;30 it seemspos- added slowly to thc solLrtioncontaining 8 at 0' until the bromine no sible, although unlikely, that radicals may be in- longer was decolorized. The resultingreaction ntixturc was poured volved in thesetransmetalations. More believableis into 100 ml of 5 lV aqueous l-rydrochloricacid solution and extracted with three 25-ml portions of ether. The combined etherealextracts the possibilitythat certainof the organometallicspecies were rvashedwith trvo 50-ml portions ot'water to remove residual formed immediatelyon mixing the reagentsare more pyridine, and analy'zed[ry'gl1tc using a 8 ft X 0.125 in. 10]i-Carbo- prone to epimerizationthan are the ate complexes wax 20M on Chromosorb I' colurnn at B0'. tretts-4-meth1'l-l- -bromocyclohexane finally presentwhen the systemhas reached equilibrium. bromocyclohexane elutes belbre cr.r--l-methy'l-l This hypothesisis supportedby the obscrvationthat on this column. cr.r-4-Nlethy'lc1'clohexl'lmercuricIlromide (ci.s-8). A mixture mixing organolithiumreagent with alkylmercurichalide conrlrtlsedof 8J",, r'i.i-flatrd 16",',lrutt.s-8 was otrtained by repeated in the absenceof copper(l)salts followed by formation liactional crlstallizittion of atr epintcric ntixtltre of 8 contposedof and reaction of a copper(l) ate complex resultsin ex- cu.40't,1 cis nratcrial. flrst fronr ethanol and tlren fronr ltentane. tensive loss of stereochemistryin the products, even Attenrpts to separate lhese diastereonters by' chronlatography under a varietl'of conclrtior-lswere unsuccessful.atrcl in fact appeared with 1. Efforts to circumvent this problem by at- to result in elrimerizationof the material appliccl to thc column.10 tempting to prepare the copper(l) ate conrplexesby The cliastereomericpuritl' of 8 w'as assayedas described above. ' reaction betweenorganomercury compound and pre- The material having [3-1";r'i.r-8 hacl mp 107-lll ancl a clitlerent formed cuprateshave not led to significantlydifferent intiared spectnrm(Kllr pellet): l-1-19(s). l14l (s). 1379(m), l37l (m). (s)"l30l (s).1236 (s). ll69 (m). ll6l (s).ll00 (s).l01l results. In 13-10 stereochemical the absence of detailed (m). 967 (m). 666 (s) cm 1. information concerningthe composition of solutions t r ur t.s-2-*l.y- droxycl'clohexl'lmercuric bromide ( t fttr rs-9)s had mp containing "lithium dialkylcuprates"and organolith- 150-152 clec(lit.e mp 1-50.-5151 .5 dec). ium-organocopper(I)ate complexes of other stoichiom- c-ra- and atultr2-meth1'lnorbornane(c.ro- tnd arulo-3). A nlixturc 63 g (0.47 nrol) of clic,rclopentadieneancl 60 g (1.-12rnol) of etries,this type of experimentneither proves nor dis- of 'fhe propeue *as heated in a Lrombfor 2.5 ltr at 230 .3; product proves the original hypothesis. Regardless,this pro- mirture rr,r,, distillecl and 20 g of colorless liquid rvasobtained at cedure holds promise as a method of preparingsolu- 5-5'(88'Iorr) (lir.1811-5.-5 115.8 (7Jl Torr)). To 3.33g of 5- tions that contain the functional equivalentof certain rnethll-2-norbornenein -50rnl ol'ethyl acetatewas added 0.30 g of types of enantiomericand diastereomericcarbanions, platinr-rmoxide. The mirturc wirsh1'clrogenateci ltncler atmospheric prcssurefor -l hr until the thettreticalamoLlnt of hydrogen was ab- and providesa method of increasingthe reactivityof ol' solvcnt and distillation yielcled 2.98 g of sorbecl. Remor,'al -forr)). many organomercuryreagents to a level which makes colorlcss liquic'ln1 -50 (71 Torr) (lit.38 125.7 126.1' (747 thern useful in organic syntheticprocedures. Valror phasechromatogralrlrl'on a 0.25 in. X l8 ft SE-710column at 90" -"-icldcdtwo pcaks at 15.3 min (2-e.r-o-methy'lnorbornane) ExperimentalSection rnin ()-crrdo-ntethl'lnort-rornane)with relative areas ol and 16.3 'fhe (lit."'i I :J.3). rnl'raredsllectra of samples Gener:rl Nlethods. All reactions of air ancl rvater sensitive 1 :3.:1.resltectivell wcrc indistinguishablefrom those re- organometallics were carriecl oiit in llanrc-dried glasswareunder collectecll'rom tltis coluntt't prepurified nitrogen using stanclard techniques.3l Diethyl ether ported by Belikova anclcow'orkcr\.:18,:re was distilled lrom calciurnhydride under nitrogen: tetrahydrofuran and other ethereal and hydrocarbon solvents were clistilled from a (33) G.Il. I(aufrnlurrtncl L. A. Tctcr,lttorg.5.ttt.,7,9 (1963)' purple solution or suspensionof disodir.rmbenzophenone clianion (34) Usc of I : I gll rrrc cliorattcrl'ft)r thcsc rccrl'stallizutitlnsoc- prior to use. Melting points were obtained on a Thomas-Hoover casionlrllylcd tcl clccorrrlr

Journal ol tlrc AntericcutClrcntical Sctciet.t' I 96:15 i Jul)'24, 1974 4943 exo-2-tert-Butylbicyclo[2.2.1]heptane (exo-4), prepared from "'a. norbornene and lerr-butyllithium following a literature proce- t dure,ao,alhad bp 55-57'(10 Torr) (lit.robp 30" (0.4 Torr)); nmr (CClr) 6 0.82(s, rerr-butyl),1.0-2.9 (m),2.2 (broad s). errdo-2-tart-Butylnorbornane (enclo-4) was prepared by oxidative coupling of lithium tert-butyl(endo-2-norbornyl)cuprate at -78. with nitrobenzene.a2,a3 The endo-4 thus prepared could be dis- tinguished from exo-4 both by glpc retention times on a SE-30 or carbowax 20M column and by nmr (the lerl-butyl resonance comes at 6 0.82 for exo-4 and d 0.92 for endo-4).ar cis-4-tert-Butylmethylcyclohexane. Hydrogenation of 35.6 g (0.2 mol) of 4-terr-butylbenzoic acid in glacial acetic acid with 2.0 g of platinum oxide as catalyst and recrystallization as described by Stolow44 yielded 10.0 g (2870 of cis-4-terr-butylcyclohexanecar- boxylic acid, mp 117-l18.5' (lit.r, mp I l7-118"). The carboxylic acid (13 g, 70 mmol) was then reduced with diborane in THF ac- cording to the procedure of Brown and Raoa6to give 13.6 g (gO7y c of cis-4-rerl-butylcyclohexylcarbinol as a waxy solid which could be distilled: bp 95" (1.3 Torr) (lit.46bp 133-136. (27 Torr)); Figure 1. ,\pparatus for low-temperature,slow addition of re- ir (CCl,) 3610(w), 3300(b),2910 (s), 1470(s). 1445(s), 1360 (s), agent: (A) precooledreagent llask; (B) reaction vessel; (C) 1025(s) cm-1; nmr (CCl,) 6 3.5 (d), 3.3 (s, OH). 2.0-1.0(m),0.9 Vibromixer;(D) coolingbatlr. (s, C(CH3)3). This alcohol (6.3 g. 37 mmol) was allowed to react with 60 ml of a pyridine solution containing 15.7 g (g7 mmol) of p-toluenesulfonyl chloride according to the procedure of Moria6 Complexes from Alkylmercury Compounds, TetrakisIhalo(tri-n- yielded (s771 and 10.4 e of cis-4-rerr-butylcyclohexylmethyl butylphosphine)copper(I)1,and tert-llutyllithium. The alkylmercury tosylate: (lit.a6 mp 93-9.4" mp 95-95.5"); nmr (CCl,r)6 7.5 (4 H, compound ( I mntol) was placed in a dry, 40-ml centrifuge tube (2 (3 m), 3.0 H, d). 2.4 H, s), 1.8 1.0(10 H, m), 0.8 (9 H, s). The containing a magnetic stirring bar and an appropriate amount of an tosylate was reduced with lithium aluminum hydride in an adapta- internal glpc standard,and the tube was stopperedand ffushedwith tion of the procedure used by Wiberg and Pfeiffer.aT A mixture of nitrogen. THF (20 ml) was added. and the resulting solution (20 6.5 g mmol) of the tosylate and 0.84 g (22 mmol) of lithium cooled to -78".51 A *78', THF solution (10 ml) containing aluminum hydride in 60 rnl of etl-rerwas refluxed for 2 days. The [ICuP(r-Bu)r]r (0.393 g. 0.25 mmol of tlie tetramer, I mequiv) was reduction was worked up as describedby Fieserand Fiesera8to give added, and the resulting solution was stirred for 5 min at -78". g (50%) 1.5 of crude product which was distilled, bp g4. (22 Torr) Slow addition of 3 mmol of lcrr-butyllithiurn (ca. 3 ml of a 1.0 l/ (lit.+s 6p 188.8"). product The cis-4-terl-butyl-l-methylcyclohex- solution in pentane) yielded a lellow solution of tl-reate complex. ane was further purified by preparative gl;rc and had nmr (CClr) This solution was allowed to stir for cu.5 min, ancl then used; (m), 6 2.0-1.2 0.92(-CH,. d), 0.9 (-C(CH,),, s). permitting the solution to stir for longer times had no discernible tretrs-4-tert-Butyl-1-methylcyclohexane. Using a published pro- influence on the y'ield or stereoselectivityof these ate complexes. cedure,503.2 g (32%il of trurts-4-tert-but.vlcyclohexanecarboxylic The addition of the rcrr-butyllithium to the solution containing acid. mp 175.5 176.5(lit.5o mp 176 177.), was prepared from l0 g RHgX and ICurPBusw&S significantly exothermic. To minimize of crude 4'te rt-butylcyclohexanecarboxylicacid. Using procedures the influenceof local heating on the stereochemistryof the copper descril'redabove. the acid was reduced to 4.2 c er 7) of crude trett.\- ate complex. the lcrl-buty'llithium solution in a separate.stoppered, 4-tert-btrtylcyclohexylmethanol. This crude product was not centrifuge tube was cooled to the temperature of the solution to distilled but was treated with 9.5 (50 mmol) of p-toluenesulfonyl r.vhichit was to be added, and then added very slowly,.with vrgorous chloride in 50 ml of pyridine as describedby Mori16 to give 6.9 g stirring, through a stainlesssteel cannula. This precaution was (86'r47 ol trarts-|-lerl-butylcl'clohexylmethyl tosylate, mp g2.5- particularly necessary when larger quantities of reagents were 83.5'(lit.a6mp 83-84'). Using the proceduresdescribed above for utilized in preparative scale reactions involving diastereomericor the cis isomer, 6.5 g (20 mmol) of this tosylate was reclucedwith enantiomericorganomercur)' reagents. g (ca. 1.0 25 mmol) of lithium aluminum hydride. The product Alkylation of the ate complex prepared using this procedure was tuns-4-methyl-terl-butylcl'clohexane{e was purified by glpc on a accomprlishedby adding 3 rnmol of alkylating agent dropwise by 0.25 in. X 8 ft SE-30 column and had nmr (CCl1) 6 2.0-1.4 (m), syringeerther neat or in THFr or pentane.2,r The resr"rltingsolution (CH3, 0.85 d),0.8-l (C(CHr)r. s); ir (CClr) 1,175(s), 1465(s). 1445 was allowed to stir at -78 for 30 min, rhen hydrolyzed by adclition (s), 1390(m), 1363(s). 124-l(s) cm-r. The trans isomer was clis- of 0.1 ml of concentratedHClat -78" or by pouring into saturatecl tinguished from the cis isomer in the nmr by the chemical shift aqueous ammonium chloride solution. The hydrocarbon phase of the methyl doublet at 0.85 and 0.92 ppm, respectively. The ir of the resultingsolution was analyzeddirectly by glpc. (CCl{) spectra of both isomers was virtually identical with the ex- Oxidative coupling of the alkyl groups present in these ate com- ception that the cis isomer has a strong peak at 1243cm-r. whereas plexeswas carried out by adding an excess(ca. I ml) of nitrobenzenc the trans isomer has a strong peak at 1233cm-1. Glpc analysis to the solution of ate complex at -78r.21,52 The resulting deep used a 0.125 in. X 8 ft SE-30 on Chromosorb W column. the rrans red solution was alloweclto stir at -78" for 30 min. hy

Bergbreiter, Whitesides I Copper(lS Ate ComplexesJ'rornAlkl'lntercurl' Reagents 4944 leakageof air into the reaction mixture that commonly occurs with B1': ir (Nu.iolmull) 1737.1311.1278, 1211.1206. 1179. 1089.772. liigh-speedstirring. After lbrmation o1'rhe atc complex, l-iodo- 720.and 680cm-'. hexane(15 ml. 100mnrol) dissolvedin l5 ml of pentanewas added Anul. Calcclfor CnH.::,BrHgOi: C. 31.61; H. 5.10. Found: slowly from the reagent part of the apparatus. The reaction mir- C.31.46:11.,s.15. ture was allowed to stir for l5 min. thcn hldroly'zed b1,,additionof Octadecl'lmercuric bromide was 1lrepared from the Grignard 100 ml of a mixturre ol' l0 ml of concenrratcd HCI in 90 rnl of reagent as describedbr, \4eals and l-raclmp I10.5 I I1.5 (lit.;, methanol. The hydrolyzed reaction mixture was poured into 2(Xl mp 110-ll1 ): ir (Nulol mull.t1456 (s), 1375(s).707 (s), and 679 ml of HzO and allowed to corne to room temperaturc. The ether (s)cm-'. layer was separatedand the aqueollslayer crtracteclrvith t"vo 100-ml t hrt' o-3-Bromomercuributan-2-olwas prepared from ci.r'-2-butene portions of pentane. Tlie combined organic phase was clriecj and mercuric acetatc r-rsingthe lrrocedureof Hofmann and g6p6l5.5r-, (MgSO.r)anci conceutrated to crr.50 ml Lrsinga rotar)'evaporator at The mercurial lias recrl'stallizeclliom ethyl acetate at -20" ancl room temperaturc. The resulting crude product was dissolveclin hacl mp 65 6(r'dec: ir (KBr pellet) 3-115(broacl). 2980 (s), 2955 50 ml of plridine and treateclw,ith a solulion ol 5 g of bromine in (s), 2930(s). l-1,18(s). 117.s(s). ll6l (s). ll-10 (m). l09B (s). 1068 20 ml of lryridine trrrtilthc bronrine color persistecl. The brontina- (s). l(X)3(s).962 (rn).910 (s).886 (m) cn.r-r; nmr (CDCl,r)6 4.30 tion reaction mirture was tlten cautiously pourecl into 100 ml of I (rn),3.00 (m). i .90(broacl s). I .;13(d), I .33(d). 1VHCl. The organic la1'erwas sellaratedand the aqueous phase Anul. Calcd for CrHgBrOHg: C, 13.59; H. 2.56. Found: was washed rvith two 50-ml ltortions of pentane. Tlre combined C. l3.5ti; H" :.67. orgauic phase was washeclriith I'our 10()-mlportions of 1 ,V HCI crytltro-3-llromomercuributan-2-ol',vas preparecl frorn lrort.s-2- to remove resich-ral1r1,ridiue. The ltentane solution \\'as coltcclt- tllltene and nrercirricucctatc rrsingthc lrroceclureof Hofnlann and trateclto a volume of cc. 2,5ml. altplieclto the top of a 2 X l5 cm Sands.i'i T'i:c mercurial u'as recr,r'stallizedfrom etliyl acetatc at colurln containing cu" 40 g of Woelrn activitl I alurnina.and cluted -20' and had nr1.r80.5 81.5'clec: ir (Kflr pellet)3100 (broad s). using pentane. Slightly'over one column volume (60 rrrl) of pen- 2980(s).2955 (s).2910 (s). l4;i2 (s), 1378(s). l167 (s), 1305(s). tane was collectecl. Vpc anallsis of the solution showecl 2.2-di- 1285(m). ll75 (s). ll0l (s). 109-s(s). I060 (s). l02l (m). 1005(s). methyloctane.3-ntethy,lnonane. and traces ( < 5'r,,)of I -iodohexane. 912 (s).890 (s) cnr 1: nmr (CDClr) 6 4.3:l(m).3.07 (m),2.07 This solr"rtionwas concentratedto a volume ol cu.2 ml. and the 3- (broads). 1.43(d). 1.33(d). methylnonane was punfied by preltarativeglpc using a 0.25 in. X Althougl-r these two diastereomershave sinrilar spectra. it was 8 ft. SE-30 on Chromosorb W column: [a]2io t1-pically,+2.0' possibletc determirretl-rc diastereorneric composition of their mix- t ' (c 5, pentane)(lit.: [q]tip +9.3 (neat)). tures witl-rEuil'ocl)r as a shift reagent. In the shifteclspectra. tlre trurt.s-2-Nleth-vlc1'clohexanolb1' N'Iethylation of the .\te Complex rnethyl groups a to the hydroxl'l coulcl be easily clistinguishedsince Formed from 2-Hvdrorycyclohexl'lmercuric Bromide, Copper(I), the\ were selrarateclb1 over ().-51tpnr. and tcrr-But1'llithium. Starting rvitl-r trutt.s-2-hydroxlclclohexll- mercuric bron-ride.tl-rc ate com;llex was preparecl b1,the ltrocedure Acknowledgments.We are indebted to our col- describedinvolving precooledreagents, with the nroclificationthat 2 leagr"resDr. P. E. Kenclallfor authenticsamples of con- mequiv of ICr-rP(r-tsu)3and 5 mmol of lcrl-butlllithiurn uas used jugateadditirrn products from llorbornylcuprates and becauseof the presenceof tl-reh1 clroxy,l protou in tl-remercurial. Reaction with nrctl.ry'lioclide (2.1 g. l5 mmol) fcr'l hr at -78' nrr-sityloriclc. to N,lr.Craig Hill for a sanrpleof trens- followeclby'stirring 1'orI hr at 0'and hydroll'siswith I nrl of con- 2-nrethoxycyclohexylrrrercuricbromide, and to Mr. centrated h1'drochloric acid gave a 41 i; yield of 2-methy'lc1'clo- Larry Trzupelcfor rnassspectra. hexanol (9lJ'1,,trans. 2'll1cis). The yield and stereochemicalpurity rverecletermined b1'analysis b1'glpc usinga0.125 in. X 8 ft TCEP (53) R. C. Larock irrtclH C. Brou'n, J. Amer. Chenr.Soc.,92,2467 on Chromosorb P column. (1e70), Ethvl ll-bromomercuriundecanoate was preparecl in 85 9," l ield (54)R. N. Mcans,J. Org. Cherrt.,9,211 (19,14). lollowing the procedure of Larock and Browns? and had mp 80- (55) li. A. Hofhrann anrlJ. Sancls,Chcttt. \er.,33.1354(1900).

Journal oJ'tlte ArtrcricanClterttical Society I 96:15 , Jul), 21, 1971