and that the resulting ROOMgX, which is highly soluble in nonpolar solvents, is also presumably nonionic, eq 8 seems to us a more plausible reaction path in this sort of system, although simple electron transfer between radicals and anions may well occur in more highly ionized systems. Experimental Section Reagents. Ether solutions of 5-hexenylmagnesium bromide were prepared either from dbromo-I-hexene or from the more available 1,2,6-tribromohexane'a and, as seen in Table I, gave (13) R.C.Lamb and R. W. Ayers, J . Org. Chem., 27,1441 (1962).
6611 equivalent results. While both lots showed about 5 73 cyclization during formation, as noted, there was no evidence for further change on storage under N2. Solutions of t-Bu00MgC1 were prepared by inverse addition of r-BuMgC1to oxygen-saturated ether at -78". The best yields (89x) were obtained using dilute (0.55 M )solutions and slow addition. Experimental runs were carried out as indicated in Table I. After reaction they were hydrolyzed with aqueous NHaC1,reduced with KI and acetic acid when necessary (run C) with quantitative titration of a sample for peroxide, dried, and analyzed by gas-liquid chromatography (glc) using internal standards and prior calibration with authentic samples. Hexene and methylcyclopentane were analyzed on a didecyl phthalate column at 70" using pentane as standard and the alcohols were analyzed on 2073 Carbowax 20M at 140"using cyclohexanolas standard.
The Mechanism of Reduction of Alkylmercuric Halides by Metal Hydrides' George M. Whitesides and Joseph San Filippo, Jr.2 Contribution from the Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139. Received April IS, 1970 Abstract: Reductive demercuration of representative alkylmercuric bromides by metal hydrides has been shown to involve generation of intermediate alkyl radicals by comparison of the product distributions obtained on demercuration with those observed on reduction of the corresponding alkyl chlorides by tri-n-butyltin hydride under free-radical conditions. Reductions of neophylmercuric bromide (1) and 1,7,7-trimethylbicycl0[2.2.l]heptyl-2mercuric bromide (2) using sodium borodeuteride, diethylaluminum deuteride, deuterio(tri-n-butylphosphine)copper(I), and tri-n-butyltin deuteride occur without the rearrangements characteristic of intermediate carbonium ions. Reductions of exo- and endo-norbornyl-2-mercuricbromides (3 and 4) with the same reducing agents yield -90: 10 mixtures of exo- and endo-norbornane-2-dl. Reductions of exo- and endo-2-chloronorbornane with trin-butyltin deuteride yield an 84: 16 mixture of these norbornane-dl epimers. The relative yields of 3-acetoxynortricyclene (13), anri-7-acetoxynorborn-5-ene(16), and exo-2-acetoxynorborn-5-ene(17) obtained on reduction of cis-exo-2-acetoxynorborn-5-ene-3-mercuric bromide (5) and exo,exo-3-acetoxynortricyclyl-S-mercuricbromide (6) with metal deuterides compare closely with those obtained on reduction of endo-2-chloro-exo-3-acetoxynorborn-5-ene (8) and exo-3-chloro-exo-5-acetoxynortricyclene(12) with tri-n-butyltin hydride. For comparison, exo-2-chloro-endo-3-acetoxynorborn-5-ene (7), endo-2-chloro-endo-3-acetoxynorborn-5-ene (9), and exo-3-chloroendo-5-acetoxynortricyclene (11) have also been reduced with tri-n-butyltin hydride. The products from reductions of these alkyl chlorides provide evidence that norborn-5-en-3-yl radicals substituted at the 2 and 7 positions interconvert rapidly through appropriate nortricyclyl radicals (e.g., 18 g 19 g 20 and 21 22 $23). Reductive demercuration of the alkylmercuric chlorides is proposed to involve intermediate alkylmercuric hydrides.
T
he development of promising procedures for the Markovnikov conversion of olefins to alcohols, ethers, and amides based on the generation of alkylmercury compounds by solvomercuration followed by demercuration using sodium borohydride has renewed interest in organomercurials as synthetic intermediates. 3 , 4 The mechanism of the solvomercuration steps in these procedures is well understood;6,6 the (1) Supported by tha National Science Foundation, Grant No. GP-
14247, and the National Institutes of Health, Grant No. GM-16020. (2) National Institutes of Health Predoctoral Fellow, 1966-1970. (3) D. J. Foster and E. Tobler, J . Amer. Chem. SOC.,83, 851 (1961). (4) H. C. Brown and Min-Hon Rei, ibid., 91, 5646 (1969); H. C. Brown and J. T. Kurek, ibid., 91, 5647 (1969); W.C.Baird, Jr., and M. Buza, J. Org. Chem., 33,4105 (1968); H.C.Brown and P. Geoghegan, Jr., J . Amer. Chem. SOC.,89, 1522 (1967); H. C.Brown and W. J. Harnmar, ibid., 89, 1524 (1967); H.C. Brown, J. H. Kawakami, and S. Ikegami, ibid., 89, 1525 (1967). (5) Reviews: J. Chatt, Chem. Rev., 51,7 (1951); N . S . Zefirov, Russ. Chem. Rev., 34, 527 (1965); W.Kitching, Organometal. Chem. Rev., 3, 61 (1968). (6) R. D. Bach, J. Amer. Chem. SOC.,91, 1771 (1969), and references therein,
mechanism of reductive demercuration using metal hydrides is less clear.' The major fraction of the evidence pertinent to the mechanism of reaction of sodium borohydride and alkylmercurials is stereochemical in nature. Reductions of methyl 2-acetoxymercuri-2-deoxy-2,3,4,6-tetra-0acetyl-0-D-mannopyranoside and related compounds,8 cis-2-acetoxybicyclo[2.l.l]hexane-3-mercuric a ~ e t a t e , ~ cis-exo-2-hydroxybicyclo[2.2.l]heptane-3-mercuricchloride, lo and trans-1 -hydroxycyclopentyl-2-mercuricacetate" are reported to proceed with predominant or exclusive retention of configuration at the carbon atom originally bonded to mercury, while reductions of eryth(7) The reduction of organomercuric halides by other chemical and electrochemical methods has been reviewed: F. R. Jensen and B. Rickborn, "Electrophilic Substitution of Organomercurials," McGraw-Hill, New York, N . Y., 1968,p 137. (8) J. H. Leftin and N. N . Lichtin, Israel J . Chem., 3,107 (1965). (9) F. T. Bond, J . Amer. Chem. SOC.,90,5326 (1968). (10) F. G. Bordwell and M. L. Douglass, ibid., 88, 993 (1966). (11) D.J. Pasto and J. A. Gontarz, ibid., 91,719 (1969).
Whitesides, San Filippo
Reduction of Alkylmercuric Halides
6612
ro- and threo-2-hydroxybutyl-3-mercuricacetate’ l and mercuric halide by a hydride donor would involve of cis- and rrans-4-methylcyclohexylmercuricchloride l 2 initial formation of an intermediate alkyl carbonium ion are reported to take place with loss of stereochemistry. by Lewis acid assisted ionization of the carbon-mercury A common mechanism for these reductions involving bond in a reaction analogous to those examined by generation of intermediate free alkyl radicals might Jensen and Ouellette, l 7 followed by conversion of this be expected to yield products with loss of stereochemcarbonium ion to hydrocarbon by reaction with metal istry in each case, while ionic or concerted mechanisms hydride. As a first step in establishing the mechanism might lead to products with retained stereochemistry. of reduction of alkylmercuric halides by metal hyHowever, each example characterized by retention of drides, we have examined the reaction of neophylstereochemistry on reduction has involved examination mercuric bromide (1) and 1,7,7-trimethylbicyclo[2.2.1]of only one of the two possible diastereomers differing heptyl-2-mercuric bromide (2) with a selection of metal in configuration at the carbon atom bonded to mercury. hydrides. The carbonium ions derived from the orWithout a complementary examination of the stereoganic moieties of these organomercury compounds chemical course of the reduction of the second diundergo well-established and characteristic structural astereomer, no convincing stereochemical or mechrearrangements at rates sufficiently rapid to be at least anistic generalization can be drawn from these studies. competitive with reduction, while the corresponding A wide variety of important organometallic reactions radicals undergo these rearrangements at much slower unrelated to demercuration involve a step in which a rates. Studies of the solvolysis of neophyl derivatives carbon-metal bond is transformed into a carbon-hyhave shown that 1,2-aryl migration proceeds concomdrogen bond.13 An interest in this fundamental class itantly with ionization,ls while aryl migration i n neoof reaction^'^,^^ has prompted us to attempt to resolve phyl radical is relatively s10w.l~rn Similarly, exthe stereochemical ambiguities posed by previous8-12 aminations of the solvolysis of norbornanes suggest studies of reductive demercuration by examination of that ionization of 2-substituted derivatives of 1,7,7the reactions of representative metal hydrides with trimethylbicyclo[2.2.1]heptane proceeds directly to the 7,-phenyl-2-methylpropylmercuricbromide (l), 1,7,7tertiary carbonium ion resulting from Wagner-Meertrimethylbicyclo[2.2.l]heptyl-2-mercuric bromide (2), wein rearrangement without passing through a discrete exo- and e~zdo-bicyclo[2.2.1]heptyl-2-mercuricbromide secondary intermediate.”,?’ Rearrangements of anal(3 and 4), cis-exo-2-acetoxybicyclo[2.2.1 .]hept-5-ene-3- ogous norbornyl radicals are very slow at room temmercuric bromide (5), and exo,exo-3-acetoxytricyclo- perature. 2 3 Thus, the absence of rearranged products C2.2.1.0Y~6]heptyl-5-mercuric bromide (6). l 6 In this paper in the reductions of 1 and 2 with metal hydrides should constitute sufficient evidence to exclude carbonium ion intermediates in these reactions. Table I lists products and yields observed on reduction of 1 and 2 using sodium borodeuteride. diethylaluminum d e ~ t e r i d e , deuterio(tri-n-butylphos~~ phine)copper(I), l 4 and tri-rz-butyltin deuteride. 25 Glpc 1 2 3 analysis of these reaction mixtures did not detect rearrangement products from either 1 or 2 in any instance. Thus, these reactions, and by inference the deniercuration reactions of the similar organoiiiercury reagents examined in the following sections, do not proceed 4 HgBr H H H H by carbonium ion mechanisms. 4 5 6 Reductions of em-Norbornyl-2-mercuric Bromide (3) and endo-Norbornyl-2-mercuric Bromide (4). In an we wish to report that the product distributions obeffort to detect possible free-radical intermediates in the served on reduction of these organoniercurp reagents reduction of alkylinercuric halides by metal hydrides, we are independent of the nature of the reducing agent, compared the composition of the mixtures of endoand to suggest that the structures of these products and exo-norbornane-2-dl obtained on reduction of esoare consistent with a mechanism of reduction involving and endo-norbornyl-2-mercuric bromide using each of intermediate free alkyl radicals.
&zc
Results Reduction of Neophylmercuric Bromide (1) and 1,7,7Trimethylbicyclo[2.2.l]heptyl-2-mercuric Bromide (2). One conceivable mechanism for reduction of an alkyl(12) Unpublished work of T. G. Traylor quoted in footnote 27 of ref 10. (13) For references to representative reactions, c f . J. P. Collman, Accounts Chem. Res., 1, 136 (1968); R . Cramer, ibid., 1 186 (1968); R. F. Heck, ibid., 2, 10 (1969); L. Reich and A. Schindler, “Polymerization by Organometallic Compounds,” Interscience, Sew York, N. Y., 1966, Chapter 4; J. P. Collman in “Transition Metal Chemistry,” Vol. 2, R. L.Carlin, Ed., Marcel Dekker, New York, N. Y., 1966. (14) G. M. Whitesides, J. San Filippo, Jr., E. R. Stedronsky, and C. P. Casey, J . Amer. Chem. SOC.,91. 6542 (1969). (15) G. M. Whitesides, E. R. Stedronsky, C. P. Casey, and J. San Filippo, Jr., ibid., 92, 1426 (1970). (16) These names are consistent with the rules of nomenclature of the International Union of Pure and Applied Chemistry. Hereafter, familiar trkidl names are sometimes used.
.lournal of the American Chemical Society
1 92:22
(17) F. R. Jensen and R. J. Ouellette, J . Amer. Chem. Soc., 83, 4477, 4478 (1961); ibid., 85,367 (1963). (18) A. H . Fainberg and S. Winstein, ibid., 79, 1608 (1957); W. H. Saunders, Jr., and R. H. Paine, ibid., 83, 882 (1960). (19) R. Kh. Freidinger, Adcan. Free Radical Chem., 1: 211 (1965); C. Ruchardt, Chem. Ber., 94, 2599 (1961. (20) For example, reduction of neophyl chloride w)ith tri-rr-butyltin hydride under free-radical conditions (AIBS, hv, 25”, neat, or ‘-10% n-hexadecane solution) leads to no detectable isobutylbenzene. (21) Reviews: J. A. Berson in “Molecular Rearrangements,” Vol. I , P.deMayo, Ed., Interscience Publishers, Sew York, S . Y., 1963, Chapter 3 ; A. Streitwieser, Jr., “Solvolytic Displacement Reactions,” McGraw-Hill, New York, N. Y . , 1962, p 126 tT. (22) H. C. Brown and H. M. Bell, J . Amer. Chem. SOC., 86, 5006 (1964). (23) D . I . Davies and S. J. Cristol, Adcan. Free Radical Chem., 1, I55 (1965). (24) G. Wilke and H. Muller, Justus Liebigs Ann. Chem., 629, 222 (1960). (25) Tri-n-butyltin deuteride was prepared by modifications of thc merhod of K . Kuhleim, W. P. Neumann, and H. Mohring, Angew. Chem., Int. Ed. Engl., 7, 455 (1968).
November 4 , 1970
6613 Table I.
Reductions of Neophylmercuric Bromide (1) and 1,7,7-Trimethylbicyclo[2.2.l]heptyl-2-mercuric Bromide (2)" ~
RHgBr
Reducing agent NaBD4 EtzAlD DCuP(n-Bu)s BusSnD NaBD4 EtzAlD DCuP(n-Bu)a Bu3SnD
2 2 2 2 5
~
~~
Product yield, %, and isotooic comoosition
Solvent
t-Butylbenzeneb 100 (85% dt) 96 (94% dd 55 (78% d ) 90 (93 dt) Bornanec 100 97
3 :1 THF-HzO Et20 3 :1 THF-Et20 None
3 :1 THF-HzO EtzO 3 :1 THF-Et20 None
Isobutylbenzene
