870 Reactionsof Alkylmercuric Halides with Sodium Borohydride in the Presenceof Molecular Oxygen' Craig L. Hill and George M.Whitesides* Contribution from the Department of Chemistry, Massachusetts Institute of Technolog)', Cambridge, Massochusetts 02 I 39. ReceiuedAugust 24, 1973 Abstract: Reaction of alkylmercuric halides with sodium borohydride in dimethylformamide saturated with molecular oxygen producesalcohols and borate estersin good yields. The products obtained following reaction of neophylmercuric bromide (l), 1,7,7-trimethylbicyclol2.2.llheptyl-2-mercuricbromide (9), and endo- and exo-nor- bornyl-2-mercuric bromides (13 and l4) with borohydride in the presenceof oxygen are compatible with a reaction mechanism involving free, noncaged,alkyl radicals as intermediates. This mechanism finds further support in the observationsthat rcaction of I with borohydride and oxygen in solutions containing2,2,6,6-tetramethylpiperidoxyl radical leads to good yields of thc prodr-rctof coupling of neophyl radical with the nitroxyl. Reaction of a-alkoxyl alkylmercuric halides with borohydridc and oxygen generatcsa-alkoxyl alcohols in good yields; similar reaction of a-hydroxy alkylmercuric halides doesnot lead to vicinal diols. [lkyl radicalsare establishedintermediates in the re- synthesis, provided that these alkyl radicals survive 11 ductiveclemercuration of alkylmercurichalides by sufficientlylong to be accessibleto reagentspresent in metal hydrides.2-a The loss of stereochemistrythat their solutions. One previous attempt to trap alkyl occursduring conversionof the carbon-mercury bonds radicals produced during reductive demercurationlead of diastereomeric2-norbornylmercury compounds into to ambigllous rr-sults: reaction of 2-norbornylmer- carbon-hydrogen bonds, the characteristic structural curic bronride with sodium borohydride in the pres- rearrangementsthat accompany demcrcuration of ence of high concentrations of di-tert-butylnitroxyl nortricyclyhnercurycompounds, and the absenceof l,- (DTBNO) produced approximately 20% of N,lf-di- 2-phcnyl migration on reduction of neophylmercuric tert-bntyl-O-2-norbornylhydroxylarnine.2 This yield is bromide combine to define the lifetimesof the inter- lower than that expectedfor reaction between free 2- rnediatealkyl radicalsin thesereactions to be short, norbornyl radicalsand DTBNO by analogywith other br"rtdo not diffcrcntiate between radical-cage mech- reactions involving this or similar scavengers,T'8but anisms(of which onc possiblesequence is reprcscnted steric hindrance may contribute to the apparent ineffi- by eq 2 and 3) and rapid radical-chain reactions (eq ciency of the coupling reaction in this instance. This 4 and 5). paper describesexperiments intended to establishcon- ditions under which alkyl radicals, generated from ]I}I RHgBr --> RHgH (l) alkylmercuric halides by reaction with sodium boro- hydride, can be diverted from the normal path leading --> .HgH (2) RHgH R. + to hydrocarbon by an external reagent. Molecular R' + 'HgH ---> RH * Hg(O) (3) oxygen was chosenas radical scavengerin theseexperi- it is highly reactivetoward RHgH---> R. (-1t mentsfor severalreasons: alkyl radicalsl'but relativelyunreactive toward organo- -> (s) R' + RHgH RH + R. + Hg(O) mercurycompoundst' and borohydrideion; it has small ancl its successfulcoupling with Since alkylrncrcuric halides are among the most steric requirements: moieties derived from organomercury reagents, readily availableand most tractableof organometallic alkyl particularly those synthesized by oxymercuration, compounds,;'';and sincetheir reductivedemercuration provide Lrseflllnew methods of forming carbon- is a particularly facile process,the reaction of alkyl- wor-rld and of adding functionality to olefinic mercurichalides with rnetalhydridcs seems potentially oxygen bonds These experimentswere also intended to attractiveas a method of-generating alkyl radicalsboth rnoieties. help to diflerentiate between the two types of mech- for mechanisticstudics and for nossiLrleutilization in anistic schemesoutlined by eq 2-5, by qualitatively (l) Supportedby tlre NationalInstitutes of Hcalth, Grants No. GM- establishingthe rapidity with which the generationand 16020ancl HL-15029, ancl by' thc National ScierrceF'ounclation, Crant No. GP-28-5E6X. (7) J. R. Thorlas and C. A. Tolman, J. Amer. Chem.Soc.,84,2930 (2) G. M. Whitcsidesand J. San Filippo, Jr.,J. Antcr.Chem. 9oc.,92, (1962): S. F. Nelsortand P. D. Bartlett,ibid.,88,143 (1966). 661I ( 1970). (8) Butyl radicals.gencratcd by reactionof rr-butyl(tri-n-butylphos- (3) G. A. Gray ancl W. R. Jackson,.1. Anter. Clrem.Soc., 91, 6205 phinc)silver(I)rvith 2,2,6,6-tetramcthylpiperidoxyl(TMPO), are scav- (1969);D. J. PastoanclJ. Gont'trz, ibid.,9l,7l9 (1969). engeclalrnost quantitativclyby this nitroryl radical in ether solution (4) Recluctionlrsing othcr rcagcntsmay take an trnrelatedcoursc: when [BuAgPBu,r]o: 0.05 M and [TMPO]o : 0.05 M: P. E. I{cndall, c/. F. R. Jensen,J. J. Miller, S. J. Cristol, and R. S. Beckley, J. Org. D. E. Bcrgbrciter,and G. M. Whitesidcs,unpublished work. Butyl Chern.,37, 4341(1912). radicals producedby photolysisof cli-n-butylbis(triphcnylphosphine)- (5) L. G. Makarova arrclA. N. Ncsrncyanov,"Methods of Ele- platinr-rrrr(II)are scavengcdwith high elicicncy by DTBNO: G. M. rrrcrtto-OrganicChcnristry," Vol. 4, North-Hollancl Publishing Co., Whitcsides,J. F. Gaasch,and E. R. Stedronsky,"/. Amer. Chent.Soc., Arrsterdam, 1967: t.. G. Makarova, "Organomctallic Reactiorrs," 94. 5258(972). Vol. 1, E. I.Bc'ckcr ancl M. Tsr-rtsui,Ed., Wiley-Interscier.lce,Ncw (9) Thc rate constantsfor rcaction of alkyl radicals rvith oxygen are York, N. Y., 1970,p I l9 ff'; Vol. 2, p 335ff. >107 l. mol-r scc 1: c/. B. Smaller,J. R. Remko, and E. C. Avery, (6) W, Kitching,Orgunometal. Chem. Rea.,3,35 (1968); W. Kitch- J. Chetrt.Phys.,48, 5174 (1968); A. A. Miller and F. R. Mayo, ./' ing in "OrganometallicReactions," Voi. 3, E. L Bcckerand M. Tsutsui. Amer. Chettt.Soc.,78,1017 (1956); C. M. Bamford and M. J. S' De- Ed., Wiley-Intersciencc,New York, N.Y., 1972,p319 tr. war, Proc. Roy. Soc.,Ser. A, 198,252(1949). [Reprinted from the Journal of the American Chemical Society, 96,870 (1974).] Copyright I974by the American Chemical Society and reprinted by permission of the copyright owner. 871 CHz --QHr (QFgnc'zo* ,r@g;n*.*-"3 @*,h:,9Hs I t-u o ( J @[1.1-. q I o --@[5,. J tt3 lrl ; ADDITION TIME ( min ) Figure 1. Product yields from reaction of neophylmercuric bromide (1) with sodium borohydride in the presenceof oxygen as a function of the addition rate of l0 ml of a 0.05 M solution of 1 to a O.23M solution of borohydride in dimethylformamide: (t) yields of neophyl alcohol (2); (o) yields of benzyldimethylcarbinol (3); and (A) yields of tert-bulylbenzene. Oxidations were carried out using 0.5 mmol of L and 0.7 mmol of sodium borohydride. r --] / r -'l Lwq)/ [RHqBrJ consumption of radical intermediates in reductive demercurationoccurs. Figure 2. Product yields for reaction of neophylmercuric bromide (1) and trcrns-2-methoxycyclohexylmercuricbromide (5) with sodium Results borohydride in the presenceofoxygen, as a lunction ofborohydride. Yields of products are representedby: (n) neophyl alcohol (2); Products. Initial experiments establishedthat the (O) benzyldirnethl'lcarbinol (3); (A) tert-butylbenzene(4); (rt reaction of alkylmercuric halides with sodium boro- Iruns-2-methoxycyclohexanol (6) ; (o) cis-2-methoxycyclohexanol hydride in dimethylformamidesolution in the presence (17): (l) cyclohexylmethyl ether (8). of molecular oxygen does yield alcohols as significant products. Using similar reaction conditions, the organomercurycompounds were sensiblyinert to oxy- CH, I xatltlr,o: gen in the absenceof'borohydride ion. The mercury- Ph-C-CHrHg Br ---------> (II) originally presentin the organomercuryreagent is I t)\rF' reducedto mercury(O)in high yield during reduction in CHt the presenceof oxygen,as it is during reductionsin the I absenceof oxygen. CH.' CHa CHt I part I I I The reaction conditionsused in the major of the ph-c= cH,roH + PhcH,-c-oH + Ph-c-cH3 (6) work reported in this paper are basedon the resultsof rll investigationsof the influenceof solvent,order and rate CHI CH' CH, 234 of addition of reagents,and work-up procedureon the 77i;$s\) 8%$%) 3%(377) yield of these alcohols. A number of dipolar aprotic solvents both dissolved and were chemically inert to yields shown without parenthesesin eq 6 are those ob- sodiumborohydride and alkylmercurichalides: DMF tained by glpc analysisof the reaction mixture without rather than dimethyl sulfoxide or hexamethylphos- work-up imrnediately after addition of the alkylmer- phoramide was selectedfor use on the basisof cost and curic halide had been completed; the yields in paren- convenienccof purification and removal in work-up. theseswere obtained by glpc analysisafter hydrolysisof Reactions were carried out by adding a solution of the reaction mixture (oide infra). Only the forn-rerare alkylmercurichalide in DMF at room temperatureto a reproduced in Figure 1. For the concentrationsand solutionof sodium borohydridein DMF through which quantities of reagents typically used in these experi- a stream of oxygen was passedrapidly; comparable ments ([RHgBr]s : 0.05 M (0.5 mmol), [NaBHrio : results were obtained by adding a solution of sodium 0.23 M (0.7 mmol)) the yields of alcoholsdid not in- borohydride to an oxygen-saturatedsolution of organo- creaseif addition of the alkylmercuric halide was car- mercury compounds. The rate of addition of the so-