STERIC STABILITY OF LITHIUM REAGENTS
May20, 1962 e 30; A ~ ~ c c5.80 L s p;
R.D. (Fig, 1) in dioxane (c 0.107 on +26', freshly prepared material): [+]66~ =too, $130'9 [+I426 +56', [+I300+521", [+I270 - 8 8 O , [+]m 6P-Bromo-5~cholestan-3-one (XI).27-A sample of this compound kindly provided by Professor Shoppee had m.p. 180" after crystallization from acetone. Shoppee and Lackz7report m.p. 155" for this compound. In a personal communication, Professor Shoppee suggested that these different m.p.'s arise from different polymorphic forms. In agreement, it was found that infrared spectra of the two forms were identical. 6~-Bromo-5a-cholestan-3-one had A%?a 282 mw, e 25; R.D. (Fig. 1) in dioxane (c 0.125): [$I650 f O O , [+]SSS -27", [$]!23 -237", [+]31~ - IOO", [+I260 1113O, [+I250 -987'; R.D. in methanol ( ~ ~ 0 . 1 0 0 )[+]a5o : -149O, I+Iss9 -140°, [+Is00 -37", [+I255 -465 .
.
1967
5~,6p-Dibromocholestan-3-one (VI).lg--.lfter crystallizing from cold ether this compound had m.p. 82-84" dec.; 5.90 p ; R.D. (Fig. 2 ) in dioxane Ad,:' 280 mp, e 150; (c 0.096): [+I650 -42,4", [ + ] s s ~ -424O, [+I307 -4134", [+I270 -794", [+]z~o- 1642 ; R.D. in isooctane ( I 0.079): [+]GO -256", [ + ] ~ s Y -248", [+I310 -3569", [+I265 - 6 5 " , [+lzsa -968". 5~-Bromo-6p-chlorocholestan-3-one (VIII).zl-.~fter crystallizing from ether-methanol, this substance had m.p. 70" 5.85 mp; R.D. (Fig. 2 ) dec.; Ad,:' 285 mp, e 50; in dioxane (c 0.103): [+le00 -255", [+]5sg --"55", [ + I 3 1 2 -2120", [+I177 -630", [ + ] z ~ o-1360". Cholestan-3-one (I): m.p. 129'; A$: 287 mp, e 25; R . D . (Fig. 1) in dioxane (c 0.108): [+]600 +170", [$1089 +1'70", [ + I n 7 +2749", [$]m -1972", [$I260 -1318'.
[CONTRIBUTION FROM NOYESCHEMICAL LABORATORY, UNIVERSITY OF ILLINOIS,URBANA, ILL.]
Effect of Solvent on the Steric Stability of Lithium Reagents1 B Y DAVIDY . CURTINA N D
WILLIAM
J. KOEHL, JR.~
RECEIVEDNOVEMBER 15, 1961
It has been found that solutions of cis-a-stilbenyllithium (&I) and of cis- and trans-2-p-chlorophenyl-1,2-diphenylvinyllithium (cis- and trans-V) in hydrocarbon solvents have very much greater stereochemical stability than in diethyl ether. Tetrahydrofuran is still much more effective than ether in promoting the isomerization of cis- t o trans-I. It has been found further that optically active sec-butyllithium in the absence of ether can be prepared and carbonated with a t least 83y0 retention of configuration. Again the isomerization (racemization in this case) is greatly accelerated even by small amounts of added diethyl ether. I t has been found that t-butyllithium can be conveniently prepared from lithium metal containing only 0 2 % sodium if the surface is coated with copper powder before reaction.
It has been demonstrated previously4 that the vinyllithium group can be formed and caused to react with a high degree of retention of steric configuration. The steric stability of a lithium compound with the structure A or B furthermore is known to be highly dependent on the nature of the
pared by a lithium-bromine exchange from the corresponding bromides in benzene-ether a t temperatures of -35' and below and react with no observable loss of configuration.ll On the other hand, a t higher temperatures or with sufficiently prolonged reaction times there was isomerization of the cis isomer to the trans, the equilibrium lying far toward the trans isomer.12 The one-sided equiRIC-Li Rz ( R = alkyl or H ) ")C=C(; Rz ; R3 librium, presumably due to the large unfavorable A B steric interaction of the two phenyl groups in the R The present paper is concerned cis isomerl3 made the study of this equilibration with another aspect of the loss of configuration of particularly attractive. The cis-a-stilbenyllithium (cis-I) was prepared such compounds, the effect of solvent. Both the formation and reactions of lithium rea- from bis-cis-a-stilbenylmercurylz(cis-11) by a gents have for many years been known to proceed lithium-mercury exchange in the appropriate much more slowly in hydrocarbon solvents than solvent. This method, rather than the more conventional ones involving lithium metal or a lithiumin solvents such as diethyl ether.1° The system chosen initially for study was the halogen exchange with butyllithium, was chosen equilibration of cis- and trans-stilbenyllithium (cis- because of the slowness of such reactions in hydroand trans-I).11-12 These two isomers had been pre- carbon solvents. The lithium reagent thus formed was then converted to the carboxylic acid(s) cis(1) Taken from the Ph.D. Thesis of W. J. Koehl, Jr., submitted to the University of Illinois, 1960. The work was presented a t the 138th Meeting of the American Chemical Society, New York, N.Y., September, 1960; Abstracts, p. 52P. A part of the work has been published in preliminary form.: (2) National Science Foundation Fellow, 1958-1960. (3) D. Y . Curtin and W. J. Koehl, Jr., Chemistvy & Induslvy, 262 (1960). (4) See D. Y. Curtin and J. W. Crump, J . A m . Chem. SOL, 80, 1922 (1958), and references therein cited. (51 R. L. Letsinger, J . A m . Chem. SOL, 7 2 , 4842 (1950). (6) R. L. Letsinger, Angew. Chem., 7 0 , 151 (1958). (7) D. E. Applequist and A. H. Peterson, i b i d . , 83,862 (1961). ( 8 ) H. M. Walborsky, unpublished results, quoted in the Communication to the Editor by H. M. Walborsky and A. E. Young, J . A m . Chem. SOL.,83, 2595 (1961). (9) D . Y. Curtin and J. W. Hausser, i b i d . , 83, 3474 (1961). (10) See K. Ziegler and H. Colonius, A n n . , 479, 138 (1930). f u r example. (11) D. Y . Curtin and E. E. Harris, J . A m . Chem. SOC.,7 3 , 4519 (1961). (12) A. N. Nesmeyanov, A. E. Borisov and N. A. Vol'kenau. I z u o s r 8 Akad. Nauk (S.S.S.R.) Oldrl. Khim. N o u k , 992 (1964).
["'>
c=c=C(EH5 H trans-I
cis-I11 or IV
c6H5)c=c(;6H,
H trans-111, X = COOH, or IV, X = C(OH)(C&)i
(13) See D. Y . Curtin, H. Gruen, Y . G . Hendrickson and H. E. Rnipmeyer, J. An. Chem. Soc., 84, 4838 (1962), for a diacurrion of the phenyl-phenyl intcmetion in other rystemr,
1968
DAVIDY . CURTINAND WILLIAM J. KOEHL,J R .
Vol. 84
(or trans)-I11 by carbonation or to the corresponding benzhydrol(s) cis- (or trans)-VI by treatment with benzophenone. The coniposition of the product mixtures was determined by ultraviolet spectrophotometry. The results are summarized in Table I. TABLE I
to the lithium with 0.2y0sodium, lithium containing 0.00570 and 2.3y0 sodium was used for reactions with l.08Y0 ether in benzene-pentane. The percentage retention of configuration was found to be unaffected by these changes in sodium content. Before any interpretation of these data can be made it is necessary to decide a t what point the ISOMERIZATION OF cis- TO ~WZS-CY-STILBENYLLITHIUM ( I ) solvent effect occurs. Thus, in the “slow” solvents, if the exchange rate is markedly slower i t might be AFTER 30 MINUTES % reten. argued that the cis-lithium compound cis-I is Yield o! tion of being formed later than in the “fast” solvents and Temp., product, configuSolvent OC. Yo ration therefore is being subjected to the isomerizing 3 : 1 ether-benzene -54 i 3 65 100“ conditions for a shorter period of time. That Tetrahydrofuran -45 =t4 73 lb this is not a major factor to be considered is shown 1: 1 ether-benzene 3-4 77 0“ by the fact that a reaction carried out in benzene1 : l benzene-pentane 2-3 69 96b pentane a t 2-3’ like those in Table I except that 2-3 23 100b the time was shortened from 30 to 8 minutes gave 2-3 68 98“ a 63y0yield as compared with the 6070 yield ob1:1 benzene-pentane with tained with the 30-minute run. Thus a t least G3% 0.54’% ether 2-3 63 81b of the lithium compound was present for 75Y0 of 1:1 benzenepentane with 2-3 .. 76b the reaction time and the increased configurational l.O8Y0 ether 2-3 55 89’ stability in the less polar solvents must be due 2-3 78 78“ primarily to a decrease in the rate of isomerization. 2-3 59 71d The further possiblity that the increased isomeri2-3 65 77“ zation in the more polar solvent is due to the inBenzene 27 f 1 49 2gb cursion of non-stereospecific exchange reactions Product of carbonation showed no evidence of the iso- in these solvents is unlikely because of the retenmeric acid. * Product of carbonation analyzed by ultration of configuration a t lower temperatures in violet spectrophotometry. Products of benzophenone ether-benzene. A more direct piece of evidence reaction with the ratio determined from the ultraviolet is provided by the report12 that a t a given temspectrum. d Product of carbonation of lithium reagent made from lithium containing 2.3% sodium. E Product perature the fraction of isomerization increases from lithium reagent prepared from lithium containing with increasing time. I n the present study i t was 0.00570 sodium. found that an increase of the time in a reaction in It may be seen that in ether-benzene (a solvent 1: 1 benzene-pentane containing l . O S ~ oether from employed because of the insolubility of the mercury 30 minutes to 60 minutes resulted in a G l % yield compound in ether alone) a t -54’ there was re- of acids cis- and trans-111, the composition of which tention of configuration in agreement with previous showed that the fraction of retention of configurawork.11J2 I n tetrahydrofuran, a solvent well tion had dropped from 76 to 48%. Similar effects of even small amounts of diethyl known to be unusually effective in promoting the formation of Grignard reagents14 a t a tempera- ether were found in a study of the equilibration of tvre (-45’) which was shown previously11,12 cis- and trans-2-~-chlorophenyl-l,2-diphenylvinylto lead to retention of configuration, there was only lithium (cis- and trans-Vi). Previous work15 had 1%retention, 99% of the carbonation product being shown that these lithium compounds are configurathe trans-acid trans-111. Similarly, raising the tionally stable for short times a t temperatures of temperature of the reactions in benzene-ether (1:1) -20’ and below but that extensive equilibration In the present work the lithium to 2-3” led to complete loss of configuration and occurred a t + Z O O . formation of the trans products. When the ether compounds cis- and trans-V were prepared from the reaction of the corresponding cis- and transwas replaced by pentane in reactions a t 2-3’, essentially complete retention of configuration mercury compounds12 cis- and trans-VI by an (96-100~0’0) was observed. I n other words, a t this exchange with butyllithium. The lithium reagents temperature replacement of the pentane by ether were then treated either with carbon dioxide or changes the steric course of the reaction from one with methanol to give a mixture of cis- and transof complete retention of configuration to complete carboxylic acids (cis- and trans-VII) or of cis- and cis-trans “inversion.” I n fact, in benzene solution trans-olefins (cis- and trans-VIII) which was anathere was 29% retention of configuration even a t lyzed by infrared analysis. The results, presented 27’ when no ether was present. The presence of in Table 11, are in good qualitative agreement with even small amounts of ether have a significant those obtained with the lithium reagent I. At effect as shown by the data in Table I. Even as -50°, even with much ether present there was substantially complete retention of configuration. little as 0.54-1.08ojO ether in 1: 1 benzene-pentane lowers the retention of configuration from 98Y0 to At 22’, however, in a solvent with much ether 78OjO0.Since the lithium metal employed was there was extensive (and perhaps complete) known to contain 0,2y0of sodium the effect of equilibration. I n benzene or cyclohexane a t 20’ sodium on the configurational stability of the without ether there was again nearly complete lithium reagent cis-I was investigated. I n addition retention of configuration and the addition of even 0.68y0 of ether lowered the Yo retention very (14) See H. Normant, “Advances in Organic Chemistry: Methods and Results,” Vol. 2, Edited by R. A. Raphael, E. C. Taylor and H. WynliPrg, Jntprsrience Publishers, I n c , Xew York. N. Y., 1960, p. 5 ff.
(15) D. Y.Curtin. H W. Johnson, Jr., and E. C. Steiner, Chem .Tor , 7 7 , 4566 (1955).
J. A m .
STERICSTABILITY OF LITHIUMREAGENTS
May 20, 1962
[
C lca.>.=C
