1796
J . Org. Chem. Vol. 37, No. 11, 1.972
HEATHCOCK, RATCLIFFE, AND VAR'
Silbert and Swern,G a ferric chloride catalyzed reaction of the perester with sodium iodide. Since the reaction is not quantitative, a standardized analytical procedure must be carefullv adhered to. The concentration ofperester is a linear function 6 the volume of thiosulfate needed to titrate the iodine liberated, but the blank and the slose of the relationshia differ somewhat from solvent to solvent. Reaction Products.-Products were determined by means of standard gas analytical techniques and by gas-liquid chromatography. Chromatographic peaks were identified by retention (6) L. S. Silbert and D. Swern, Anal. Chem., 80, 385 (1958).
time and by their infrared spectra using an att,enuated total reflectance device.
Registry No.-Cumyl peracetate, 34236-39-0; toluene, 108-88-3; CC14,56-23-5; pyridine, 110-86-1. Acknowledgment. -The authors wish to acknou.1edge support of this work by the Army Research Office,Durham, and in part by the Institute of Arthritis and Metabolic Diseases.
Synthesis of Hydroazulenes by Solvolytic Rearrangement of 9-Methyl-1-decalyl Tosylatesl CLAYTON B. HEATH COCK,"^ RONALD RATCLIFFE,) AND JAMES VAN4 Department of Chemistry, University of California, Berheley, California 94720 Received August 27, 1971 9-Methyl-1-decalyl p-toluenesulfonates 1-4 and 3-d have been synthesized and their solvolyses studied. Transfused tosylates 1 and 2 yield predominantly hydroazulenes (54, 55, 33, and 36). cis-Keto tosylate 3 yields predominantly the unrearranged octalones 13 and 15. cis-Deoxy tosylato 4 yields substantial amounts of both rearranged products (hydroazulenes 33 and 36) and unrearranged octalins 14 and 18. No methyl-migrated rearrangement products are obtained in any case. Tosylates 1-4 undergo first-order acetolysis a t 100' with relative rates of 1:319: 10.8: 352. cis-Keto tosylate 3 solvolyzes 1.55 times faster than its monodeuterated analog, 3-d. The results are interpreted in terms of a mechanism involving rate-limiting ionization, without participation of the rearranging bond, to an intimate ion pair, which undergoes stereospecific rearrangement to yield hydroazulene or deprotonation to yield hydronaphthalene. With the cis-keto tosylate 3, a conformation is available in which the initial ion pair may decompose with hydride participation to yield a new decalyl cation 58, the immediate precursor of the unrearranged products
We have recently discussed a stereorational route to guaiasulenic sesquiterpenes which involves (a) construction of an appropriate decalinic intermediate, (b) establishment of the relative stereochemistry of the eventual guaiazulene using established conformational principles, and (c) solvolytic rearrangement of the intermediate to the required hydr~azulene.~The route has been applied to the total synthesis of the sesquiterpenes b ~ l n e s o l , ~ac-bulnesene,6 ,~ and kessane.6 As a prelude to that work, we studied, as model substances, the solvolysis of the 9-methyl-1-decalyl-p-toluenesulfonates 1-4. I n this paper we report the results of those preliminary studies. TsO
SCHEME I
H
H
6
38
2
1
Wolff -Kishner pyridine. @
reduction.
b
p-Toluenesulfonyl
chloride]
The cis-keto tosylate 3 was prepared by a route previously reported.s cis-Deoxy tosylate 4 was prepared from acetate 79 as outlined in Scheme 11. SCHEME I1
I, X=O 2, X -
H2
3, X = O
4,X=H2
Synthesis of Tosylates 1-4. -The trans-fused tosylates 1 and 2 were synthesized from keto alcohol as outlined in Scheme I. (1) Presented in preliminary form: (a) C. H. Heathcock, R . Ratoliffe, and C . Quinn, 158th National Meeting of the American Chemical Society, New York, N. Y., Sept 10, 1969; (b) C. H. Heathcock and R . Ratcliffe, Chem. Comrnun., 994 (1988). (2) Fellow of the Alfred P. Sloan Foundation, 1967-1969. (3) Kational Institutes of Health Predoctoral Fellow, 1967-1970. (4) Participant in a National Science Foundation Summer Research Program for High School Teachers, 1968. (5) C. H . Heathcook and R. Ratcliffe, J . Amer. Chem. Soc., 98, 1746 (1971). (6) M. Kato, H. Kosugi, and A. Yoshikoshi, Chem. Commun., 185, 934 (1970). (7) A . J. Birch, E. Pride, and H. Smith, J . Chem. Soc., 4688 (1958).
7 a Hz-Pd/SrC08. ride] pyridine.
Y
8 b
Wolff -Kishner.
0
p-Toluenesulfonyl chlo-
The configuration at the three centers of asymmetry in tosylates 1-4 follows from the methods of synthesis. Corroborative evidence is obtained from pmr spectroscopy. Recent observations of the proton signals adjacent to the p-toluenesulfonate group in thc four isomeric 1-decalyl tosylates indicate a half-band (8) C. H. Heathcock, R . A. Badger, and J. W. Patterson, Jr., J . Amer. Chem. Soc., 89, 4133 (1967). (9) C. E. C. Boyce and J. S. Whitehurst, J . Chem. Soc., 2680 (1960).
J. Org. Chem. Vol. 37, No. 11, 1972
SYNTHESIS OF HYDROAZULENES width of 18-20 Hz for an axial proton and 6 HZ for an equatorial proton.1° An apparent exception, in which this resonance has a half band width of 13 Hz, was attributed to conformational equilibrium. Similar results were obtained for tosylates 1-4. Half band widths of 17-18 Hz for compounds 1, 2, and 4 are indicative of an equatorially disposed p-toluenesulfonate group, while the WI,, of 12 HZ for isomer 3 suggests a mixture of conformations.1° The transfused tosylates 1 and 2 have available only a single low-energy conformation, in which the p-toluenesulfonate group is equatorial. Analysis of the cis-fused tosylates 3 and 4 is complicated by conformational equilibrium. The observed WIl, of 17 Hz for compound 4 indicates a preponderance of conformation 4a, whereas the value of 12 Hz for compound 3 suggests a more equal population of conformations 3a and 3b. For the cis-dcoxy compound 4, the steroid conformation 4a should predominate to the extent that the p-tolucnesulfonate grouping prefers an equatorial position.” Introduc-
Gk
1797
SCHEME I11
11
10
5
LiAlD4.
b
HsO +.
0
12 3d p-Toluenesulfonyl chloride, pyridine.
mental Section), we synthesized a number of possible products. Other solvolysis products were isolated and identified by a combination of spectroscopy and degradation. The presence of one solvolysis product was inferred from indirect evidence (vide infra). Octalone 13 was prepared as previously reported.s Wolff-Kishner reduction of 13 gave octalin 14. Octalone 15, which was isolated from a solvolysis of
H
14
13
1,x-0
2 , X = H2
the cis-keto tosylate 3, was shown to have an unrearranged skeleton by its hydrogenation to cis-decalone 16.l 4 The corresponding hydrocarbon, compound 18, was prepared by Wolff-Kishner reduction of the known octalone 17, the Diels-Alder adduct of 1,3butadiene and 2-methylcyclohexenone. l5 3a, X = 0 4a, X = H,
3b,X=O 4b, X - H,
15
tion of the carbonyl group brings the “3-alkyl ketone effect” into play,12 thus reducing the energy of conformer 3b rclative to that of 3a.13 A deuterium analog of the cis-keto tosylate 3, which was used subsequently for mechanistic studies, was synthesized from the known ketal epoxide lo8 as shown in Scheme 111. Since epoxide 10 is known to suffer nucleophilic ring-opening at the less hindered position,8 the structure of the deuterated tosylate may be assigned as 3-d. Compound 12 was shown by mass spectrometry to contain 0.97 atom of deuterium per molecule. Synthesis and Identification of Solvolysis Products.Preliminary experiments showed that, although tosylates 1-4 undergo solvolysis to give only two or three major products in each case, several minor products are formed (vide infra). Since we planned to analyze our solvolysis mixtures by capillary glpc (see Experi(10) C. A. Grob and S. W.Tam, H e h . Chim. Acta, 48, 1317 (1965). (11) Jensen giveti the A value of the p-toluenesulfonate group at -SO0 in CS2-CDCla as 0.515 I 0.021 kcal/mol: F . R . Jensen, C. H. Bushweller, and B. H. Beck, J . Amer. Chem. Soc., 91, 344 (1969). (12) W. Klyne, Bxperientia, 12, 119 (1956). (13) Allinger gives a value of 0.6 kcal/mol for the 3-alkyl ketone effect when the alkyl group is methyl: N. L. Allinger and L. A. Freiberg, J . Amer. Chem. Soc., 84, 2201 (1962).
16
d-03 17
18
The trans-fused octalone 19 was prepared by refluxing trans-keto tosylrtte 1 with lithium chloride in dimethylacetamide. The crystalline octalone 19 is obtained in 70% yield. Wolff-Kishner reduction of octalone 19 yields the corresponding hydrocarbon 20. Because of the severe treatment necessary to dehydro tosylate 1,16and since the more stable location for a double bond in a trans-decalin is between carbons
1-CQo43 8.
H
19
20
(14) W. G. Dauben, J. B . Rogers, and E. J. Blanz, ibid., 76, 6384 (1954). (15) A. M. Gaddis and L. W. Butz, i b i d . , 69, 117 (1947). (16) Compound 1 is recovered unchanged (98% recovery) after refluxing in pyridine for 48 hr. In oontrast, isomer 8 undergoes smooth dehydrotosylation when refluxed in this solvent for 16 hr.8
1798 J . Org. Chem. Vol. 37, No. 11, 1972
HEATHCOCK, RATCLIFFE, AND VAN
2 and 3," we sought independent confirmation for structure 19.18 Ketalization of 19 gives a crystalline dioxolane 21, which is oxidized by m-chloroperbenzoic acid to obt'ain a single cryst'alline oxide, 22, in 67% yield. That only one epoxide is formed is shown by pmr spectroscopy (a single angular methyl resonance at T 9.07) and glpc. The assigned stereochemistry of the epoxide ring is based on the assumption that the trans-decalone 2 1 suff ers predominant electrophilic at't'ack from the less hindered face. Reduction of 22 wit'h lithium aluminum hydride, followed by ketal hydrolysis, gives a ketol 23 (clearly different from ketol 5 ) which is oxidized by Jones reagentl9 t o the known diketone 24.'
-
19 + m o a
4 21
oa
H
0-J
22
H
H
25
26
H
H
28
29
H
n
carbinol mixture 32, which reacts with phosphoryl chloride in pyridine to give a hydrocarbon mixture. Capillary glpc analysis reveals that the mixture contains five components in a ratio of 72 : 15: 10 :2 : 1. The major dehydration product was obtained in a pure state by preparative glpc. It was assigned structure 33 on the basis of its pmr spectrum (vinyl methyl absorption at T 8.37, no vinyl proton resonance) and the degradative evidence to be given below. The pmr spectrum of the crude dehydration product has absorption at T 5.35 (exocyclic methylene) and 4.52 (endocyclic vinyl proton) , attributable to compounds of type 34 and 35 (stereochemistry unknown). Coinjection experiments showed that the product formed in 2% yield is isomer 36 (vide infra).
bo-ho H
H
23
24
In order t o examine the possibility of methyl-migrated decalinic products in the solvolysis mixtures, a mixture of 1-methyloctahydronaphthaleneswas synthesized. Hydrogenation of 1-naphthol by the method of n/leyers20affords a mixture of 1-decalols and l-decalones. Oxidation of this mixture by Jones reagent,19 followed by equilibration with aqueous sulfuric acidbenzene, yields a 9 : 1 mixture of epimeric 1-decalones ( 2 5 ) with tmhetrans isomer predominating. Treatment of this mixture with methyllit'hium in ether gives, after chromatographic purification, the tertiary carbinol 26. Treatment of alcohol 26 with phosphoryl chloride in pyridine affords a hydrocarbon mixture in 87% yield. Capillary glpc analysis reveals that the product is a mixture of four compounds in a ratio of 65: 20: 12:3. Analysis of the pmr spectrum, using the signals at 7 8.42 (vinyl met'hyl), 5.45 (exocyclic methylene), and 4.78 (endocyclic vinyl proton), indicat,es that, the three major products are isomers 27 W%),28 (20%), and29 (12%). A similar mixt'ure of 4-methyloctahydroazulenes was synthesized from the known enone 30.21 Lithium-ammonia reduction of 30 gives a 60:40 mixture of decahydroazulenones 31, in which the more stable t'rans-fused isomer22 is presumed to predominate. Treatment of 31 with ethereal methyllitmhiumgives a (17) (a) E. J. Corey and R. A. Sneen, J . Amer. Chem. Soc., 77, 2505 (1955); (b) R.Bucourt, Bull. Soc. Chim. Pr., 1262 (1963). (18) There was actually a further reason to be anxious about the placement of the double bond in 19. I n the pmr spectrum of 19, the two vinyl protons appear as a sharp singlet. I n the cis series, isomer 16 has a sharp two-proton singlet in the vinyl region, b u t isomer 13 has complex absorption, with both protons clearly discernible as (roughly) tripled doublets. (19) A. Bowers, T. G . Halsall, E. R. H. Jones, and 9.. J. Lernin, J . Chem. Soc., 2548 (1953). (20) A.I. Mepers, W. Beuerung. and G. Garcia-Munoz, J . O w . Chem., 29, 3427 (1964). (21) A. G. Anderson and J. 8.Kelson, J . Amer. Chem. SOC.,78, 232 (1951). (22) J. A. Marshall and W.F. Huffman, ihid., 92, 6358 (1970).
H
30
H
31
32
&+&+&+& H 33
H
H
36
35
34
Hydrocarbon 33 was also prepared and characterized in the following manner. Acetolysis of transketo tosylate 1 gives a mixture of four Cl1HlaO bicyclic keto olefins, in the ratio 78: 10:7 : 5 (vide infra). Wolff-Kishner reduction of this mixture gives a mixture of four bicyclic CllHls olefins in the same ratio. The major constituent of this mixture is identical, both spectrally and chromatographically, with the major product from the dehydration of 32. Ozonolysis of the mixture yields a mixture of carbonyl compounds. The major product, purified by preparative glpc, was identified spectrally as 37.
H
36
37
33
Hydrocarbon isomer 36 could not be separated from any of the solvolysis or dehydration mixtures in quantities sufficient for direct examination. Its structure was therefore deduced by the following method. A solvolysis mixture (bicyclic C11H18olefinic), shown by isolation and glpc coinjection experiments to be a mix-
J. Org. Chem. Val. 37, N o . 11,19W
SYNTHESIS OF HYDROAZULENES ture consisting of 78% 33, 10% 20, and 5% of another isomer (36)) was treated with 0-naphthalensulfonic acid in refluxing acetic acid. The isomerization was monitored by glpc analysis. After equilibrium had been achieved, the 33 :20: 36 ratio had changed from 78:10:5 to 28:14:52 (see Table 11). Thus, isomer 36 is obtained at the expense of isomer 33, and most probably has the same carbon skeleton. Since the pmr spectrum of the equilibrated mixture shows increased saturated methyl absorption at 7 9.08-9.20, corresponding decreased vinyl methyl absorption a t T 8.36, and no new vinyl proton absorption, we have assigned isomer 36 the indicated structure. Solvolysis of Tosylates 1 4 . Products.-Tosylates 1-4 were solvolyzed in buffered acetic acid. Keto tosylates 1 aind 3 give mixtures of bicyclic CllH160 keto olefins. Deoxy tosylates 2 and 4 give mixtures of bicyclic CllHl8 olefins. I n order t o facilitate comparison, the keto olefin mixtures were submitted to Wolff-Kishner reduction before analysis. The hydrocarbon product mixtures were then analyzed by capillary glpc on two different columns (see Experimental Section). The results are shown in Table I. TABLE I ACETOLYSIS PRODUCTS FROM TOSYLATES 1-4" Retention time, min Re1 retention time
14
18
20
6.20
6.30
6.39
36
7.12
33
Otherb
7.38
0.85 0.87 0.96 1.00 0 10 5 78 7 (3) Oc Oc 14O 5 2 ~ 280 6c (2) 2 0 0 0 15 80 5 (2) 3 74 13 0 0 9 4 (2) 4 35 4 0 24 30 7 (2) a Acetolyses were performed a t 118' in glacial acetic acid containing 2 equiv of anhydrous KOAc. Keto olefins were reduced to hydrocarbons for analysis. The analyses were performed on a 150 ft X 0.01 in. SF 96 column at 105'. Composition was determined by peak heights (TVi/, < l mm). b The number of unidentified compounds is given in parentheses. c Composition of the acid equilibrated mixture. 1
0.84 0
As -shown in Table I, the major acetolysis products from the trans-fused tosylates are hydroazulene olefins. I t is notable that the nonrearranged octalin 20, which is obtained in 10% yield from trans-lieto tosylate 1, is not formed at all in the acetolysis of trans-deoxy tosylate 2. Methyl-migrated octalins (e.g., 27, 28, or 29) cannot be detected in the product mixture from either of the trans-fused tosylates. Acetolysis of trans-deoxy tosylate 2 is remarkably clean, giving at least 95% of hydroazulene products 33 and 36.
I n the cis-fused series, the situation is much more complicated. The cis-lieto tosylate 3 gives a total 18) and only 9% of 87% nonrearranged olefins (14 of identifiable hydroazulene product. On the other hand, cis-deoxy tosylate 4 gives more rearranged (54%) than inonrearranged material (39%). Again, methyl-migrat ed products are not produced. In order to test the effect of reaction conditions on the composition of the product mixtures, deoxy tosylates 2 and 4 were solvolyzed in various media, under various conditions. The results are shown in Table 11.
+
1799
Acetolysis of Tosylates 1-4. Kinetics.--The rates of solvolysis of tosylates 1 4 and tosylate 3-d were determined in acetic acid at 100". Kinetics were determined b y potentiometric titration of the liberated acetic acid with sodium acetate.23 The infinity titers, observed after at least 10 half-lives at the reaction temperature, were used to calculate first-order rate constants. The results are summarized in Table 111. The observed rates are cleanly first order and, as shown in Table I11 by the small average deviations, are reproducible. I n Table IV, a comparison is made between t'he kinetic dat'a obtained in t'his study and that for related compounds 38-42. Since the substitution patt'ern a t C-9 in tosylates 1-4 can be regarded as two alkyl groups, 2,2-dialkylcyclohexy1 tosylates 40 and 41 are particularly suitable models. Comparison of the available data indicates that compounds 2, 4, 40, and 41 solvolyze with nearly identical rates and demonstrates the suitability of the model. Recent studies have shownz4that pinacolyl brosylate, which undergoes acetolysis three times faster t'han isopropyl brosylatelZ5solvolyzes in trifluoroacetic acid with rate-determining ionization to a tight ion pair. Similar arguments may be advanced for solvolysis of tosylates 40 and 41, which are regarded as undergoing ratedetermining ionization without participation, even though both yield mainly ring-contract'ed productsaZ6 Furthermore, tosylates 2 and 4 solvolyze only 10.3 and 3.2 times faster than their demethyl analogs 38 and 39, respectively, and about' three times faster than cyclohexyl tosylate (42). Alt'hough small rate increases (tenfold or less) have been attributed to neighboring-group participation,*' such explanations must be regarded with caution. I t appears that the slight rate enhancements found for tosylates 2 and 4 over compounds 38, 39, and 42 are the result of ordinary inductive contributions and st'eric effect's. Mechanistic Considerations. -The solvolysis of transdeoxy tosylate 2 is illust'rated in Scheme IV. Solvolysis is assumed t o proceed by a slow unimolecular heterolysis to give the short lived "cationoid" species 43. Since individuality is maintained, as evidenced by the absence of methyl-migrated products, this species probably exists as an intimate ion pair28 wit'h the departing tosylat'e anion. I n addition, since the kinetic studies reveal no anchimeric assistance t'o ionization, the products are determined by rapid rearrangement to t'he thermodynamically more stable carbonium ion 44 (or ion pair) after the first transition state has been passed. It is an important feature of this reaction type t'hat the migrating bond must be suitably placed t'rans and coplanar to the leaving group in order that the migrating electrons can attack the free lobe of the orbital at C-1 while the tosyl group may still be weakly bonded. Carbonium ion 44 can (23) W. Winstein, E. Grunwald, a n d L . L. Ingrahm, J . Amer. Chem. Sac., 70, 821 (1948). (24) 5'. H. Shiner, R. D. Fisher, and W.Dowd, ibid., 91, 7748 (1969). (25) (a) S. Winstein, B. K. Moore, E. Grunwald, I
