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J. A. BERSON,A. REMANICK, S. SUZUKI, P. REYNOLDS-WARNHOFF AND D. WILLNER
[CONTRIBUTION FROM
THE
Vol. 83
DEPARTMENT OF CHEMISTRY, UXIVERSITY OF SOUTHERN CALIFORNIA, Los ANCELES7, CALIF.]
The Absolute Configurations of Some Simple Norbornane Derivatives. A Test of the “Conformational Asymmetry” Modell” BY JEROME A. BERSON,JASJIT SINGH WALIA,ALLENREMANICK, SHIGETO SUZUKI, P. REYNOLDS-WARNHOFF AND DAVIDWILLNER’~ RECEIVED FEBRUARY 24, 1961 Absolute configurations and maximum rotations are deduced for forty-six norbornane derivatives by conversion of %endoacids to camphenilane. Optical resolutions of both norborneol to fenchone and of the 2-methyl-5-norbornene-2-carboxylic epimeric 2-methyl-5-norbornene-2-carboxylic acids are described, that of the exo-acid being apparently virtually complete. The conformational asymmetry model correctly predicts the signs of rotation for a number of these substances, but gives incorrect predictions for six norbornane derivatives, the configurations of which can be deduced from information in t h e literature.
In the course of other studies, we have established the relative and absolute configurations of a number of norbornane derivatives. We anticipated that these correlations would be useful in studies of reaction mechanism in this series and also in providing a test of recently proposed methods of relating absolute configuration and sign of optical rotation. The present paper summarizes our stereochemical results. Our assignments of absolute configuration were based upon conversions of simple norbornanes to derivatives of naturally-occurring terpene substances for which absolute configurations had already been deduced. The transformations were effected in two separate series, one leading from 2monosubstituted norbornanes to fenchone and the other from 2,2-disubstituted norbornanes to camphenilane. Correlation of 2-Monosubstituted Norbornanes with Fenchone.-The stereochemical correlations of the natural monoterpenoids with glyceraldehyde had been established by a network of internally consistent relationships involving, in the final stages, both physical2 and chemical3 evidence. Chart 1 outlines the steps by which we converted (+)-endo-norborneol (I) to (-)-fenchone (VII), thereby establishing the absolute configurations of I, the intermediate substances 11-VI and a series of other norbornane derivatives already related to I (the arabic numbers refer to Table I). The configurations shown are absolute for the indicated enantiomers. The optically active (+)-endo-norborneol (I) used as starting material was prepared by resolu(1) (a) Thisresearch wassupported in part by the United States Air Force through the Air Force Office of Scientific Research of the Air Research and Development Command under Contract No. AF(G00)1544. Reproduction in whole or in part is permitted for a n y purpose of the United States Government. Also supported in part by a grant from the Petroleum Research Fund administered by the American Chemical Society. Grateful acknowledgment is hereby made t o the donors of this fund. We are also indebted t o the National Science Foundation (Grant NSF-G 11386) and t o the Alfred P. Sloan Foundation for support of part of this work. (b) On leave of absence from the Weizmann Institute of Science, Rehovoth, Israel. (2) (a) A. Fredga and J. K. Miettinen, A c f a Chem. Scand., 1, 371 (1947); (b) J. Porath, Arkiv Kemi, 1, No. GO (1950). (3) (a) K. Freudenberg and W.Hohmann, A s n . , 684, 54 (1954): (b) D. S. Koyce and D. B. Denney, J . A m . Chem. Soc., 76, 768, 3630 (1954): D. S. Noyce and J. H. Canfield, ibid., 76, 3630 (1954). (c) For a summary of Yelatiwe configurations within the terpene series, see W. Hiickel, J . p r a k f . Chenz., 157, 225 (1941). For summaries of absolute configuration, see (d) J. A. Mills and W. Klyne in “Progress in Stereochemistry,” W. Klyne, ed., Butterworths Scientific Publications, London, 1954, p. 177; (e) A. J. Birch, Ann. Reporls Pvog. Chem., 47, 191 (1950).
tion of the corresponding acid phthalate via the brucine and cinchonidine salts, according to the procedure of Winstein and T ~ - i f a n . ~Our ” starting material was incompletely resolved, the resolution being pursued only to acid phthalate of [ a ] D -3.21°, 64% of the highest rotation r e p ~ r t e d . ~ The manipulations involved in the steps of Chart 1 were carried out without recrystallization of any of the intermediates, and consequently optical CHART1 Cr03 acetone
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fractionations were not a factor. The identity and purity of each product were established by comparison of the infrared spectrum and vapor chromatographic retention time with those of authentic racemic material obtained by carrying through the entire scheme in the racemic series. (4) (a) S Winstein and D. Trifan, J . A m . Chem. Soc., 74, 1147 (1952); (b) 74, 1154 (1932).
Oct. 5 , 1961
CONFIGURATIONS OF SIMPLE NORBORNANES
3987
Each of the steps in the racemic series had I11 to I V had to be chosen so that the sacrifice of been described by others, and our procedures this method of purification would cause no difficulty. followed those reported except for minor but im- The conditions finally used were dangerously close portant modifications. Three steps of the scheme to those under which complete racemization would were potentially troublesome: the oxidations of have occurred; a control experiment showed that endo-norborneol (I) and 1-methyl-exo-norborneol when optically active IV was re-exposed to the re(V) to 2-norbornanone (11) and l-methyl-2- action conditions, it lost all optical activity. The norbornanone (VI), and the Wagner-Meerwein fraction of optical activity lost in the rearrangerearrangement of 2-exo-methyl-2-endo-norborneol ment step can be calculated on the assumptions that (i) the reported highest rotations for endo(111) to 1-methyl-2-exo-norbornyl acetate. The oxidation of optically active 2-exo-norborneol norbornyl acid phthalate4 and fenchone7 corwith dichromate and sulfuric acid had been re- respond to optically pure materials and (ii) that no ported4 to give 2-norbornanone with partial loss other steps of Chart 1 produce racemization. On of optical purity, presumably4 because of prior this basis, the rearrangement occurred with loss partial racemization of the very sensitive exo- of 55% of optical purity.s An ambiguity is present in the scheme of Chart alcohol in the strongly acidic medium. Under the same conditions, 2-endo-norborneol gave ke- 1 if one admits the possibility that 6,2-hydrogen tone with higher retention of optical purity.4 shift in the cationic intermediate (VIII or a bridged IV rearrangeThe maximum optical rotation of the ketone had non-classical variant) in the 111 not been established, however, and therefore it ment can occur in concert with attack of solvent was not clear that the latter oxidation gave com- (cf. VI11 + IX). If this hypothetical process were plete retention of optical purity. Since we feared faster than direct attack of solvent a t the cationic that a later step (I11 + IV) might also produce partial racemization, i t was necessary to conserve our hard-won optical activity. Accordingly, we investigated other methods for carrying out the oxidation. Oppenauer oxidation (quinone-alumiIX num t-butoxide-benzene5) of optically active I VI11 gave optically active I1 in 51y0 yield. Oxidation site of VIII, the predominant product would be with chromium trioxide-sulfuric acid-acetone6 IX, the enantiomer of IV, and all the configurations gave I1 with the same amount of retention of of the scheme would be reversed. We feel that optical purity observed in the Oppenauer procedure ; this possibility can be dismissed as unlikely, after careful scrutiny of the conditions for the primarily on the grounds that in the single analochromium trioxide oxidation, the yield was raised gous case for which direct evidence is available, the to 85%. Racemization in the Oppenauer oxidation process, if present a t all, a t least does not control was inherently improbable; even less probable the stereochemical result. Thus, (+)-a-pinene was the possibility that partial racemization oc- (X) can be converted1' to esters of (+)-borneol curred in the Oppenauer oxidation to exactly the (XII), the indicated relative configurations being same extent as in the chromium trioxide oxidation. assigned on the assumption that direct conversion Accordingly, both oxidations must have occurred of the intermediate cation XI to product of rewith complete retention of optical purity. This tained configuration (XII, pat'h a) is faster than desirable result combined with the high yield and concerted reaction with solvent and hydrogen convenience made the chromium trioxide pro- migration to product of inverted configuration cedure the method of choice. In the oxidation (XIII, path b). That this assumption must be of V to VI, the Oppenauer and chromium trioxide correct is established by the independent correlamethods again gave identical amounts of retention tion of a-pinene and borneol through a-terpineol of optical purity, indicating the absence of race- (XIV). l 2 By analogy, we assume. that the reaction mization. (7) 0. Wallach and P. Vivck, Ann., 362, 174 (1908). The conversion of 2-methyl-2-endo-norborneol (8) It is not entirely clear t h a t the resolution48 of endo-norborny (111) to 1-methyl-2-exo-norbornyl acetate (IV) acid phthalate was complete.9~10 Accordingly, this figure may require by Wagner-Meerwein rearrangement was poten- revision when the maximum rotation of t h e acid phtha!ate is estabtially hazardous to the scheme because of the pos- lished. (9) J. A. Berson and S. Suzuki, J. A m . C h e w SOL.,81, 4088 (1959). sibility of rapid 6,2-hydrogen shift and/or tri(IO) (a) J. A. Berson and D. A. Ben-Efraim, ibid., 81, 4094 (1959); cyclene formation which would cause racemiza- (b) 81,4083 (1959). (11) J. Reisman, Bzdl. SOC. chim. France, [41 41, 94 (1927); M. tion. In fact, the rearrangement of optically J. Reisman and E. Suau, i b i d . , [4] 47, 966 (1930). active I11 to IV did result in extensive (but fortu- DklCpine, (12) (+)-=-Pinene (X)is converted by acids t o (+)-a-terpineol nately incomplete) racemization. Since recrystal- (XIV).30 I t can hardly be doubted t h a t the relative configurations lization of the product or a derivative could not of these two substances a r e as shown and. in any case, t h e matter is be relied upon for fear of optical fractionation, settled independently by the o b s e r ~ a t i o n 't~h ~a t~ X~ and X I V can be oxidized to enantiomeric forms of the same ketolactone XV. Niconditions that assured complete conversion of trous acid deamination of (+)-bornylamine (XVI) gives (+)-a--+
( 5 ) Cf. P. D. Bartlett and W. P. Giddings, J . A m . Chem. SOC.,82, 1240 (1960). (6) (a) R. G. Curtis, I. Heilbron, E. R . H. Jones and G. F. Woods, J . Chem. So
