3790
J . Org. Chem. 1 9 8 0 , 4 5 , 3790-3797
experiment, averages signals, and processes the data. The instrument allows the monitoring of transient phenomena in the lO-ns-lOO-ps time range. Further details have been given else-
Acknowledgment. We thank the Department of Science and Technology, Government of India, Indian In(35) M. V. Encinas and J. C. Scaiano, J. Am. Chem. Soc., 101, 2146 (1979). (36) L. K. Patterson and J. C. Scaiano, to be published.
stitute of Technology, Kanpur, and the Office of Basic Energy Sciences of the US. Department of Energy for financial support of this work. We also thank Dr. N. Selvarajan for partial experimental assistance in determining the quantum yields of some of the samples. Registry No. 9, 66933-94-6; 10, 73367-64-3; 11, 73395-35-4; 12, 73367-65-4; 13, 73464-65-0; 14, 73367-66-5; 16, 73367-67-6; 21, 73367-68-7; 23, 73395-62-7; 26, 73367-69-8; 27, 73367-70-1; 28, 56585-39-8; 33, 73367-71-2; 34, 73367-72-3; 35,1096-50-0; 36,7336773-4; biphenyl, 92-52-4.
Photochemical Pathways for the Interconversion of Nootkatane and Spirovetivane Sesquiterpenes’ Drury Caine,* Chia-Yeh Chu, and Samuel Lindsay Graham School of Chemistry, Georgia Institute of Technology, Atlanta, Georgia 30332
Receiued February 1, 1980 Tricyclodecenones 2a and 2b, prepared by irradiation of the corresponding cross-conjugated dienones in anhydrous dioxane a t 254 nm, were converted into the spiro dienones 4a and 4b, respectively, on irradiation in aqueous acetic acid with ultraviolet light of wavelengths >300 nm. Irradiation of tricyclodecenone 11 for 30 min under similar conditions gave anhydro-P-rotunol (12), the bicyclic trienone 13, and 3,4-dehydronootkatone (lob) in 46, 37, and 12% yields, respectively. However, monitoring of the course of the reaction by GLC indicated that 12 and 13 were formed in an initial ratio of 7:3 and that 13 and also 10b were produced by further rearrangement of 12. This was shown to proceed via the intermediate bicyclohexenone derivatives 16. An independent stereospecific synthesis of the bicyclic trienone 13 from (-)-2-carone was developed. Tricyclodecenone 17, derived from 13, gave a mixture of lob, 12, and 13, in 20,40, and 15% yields, respectively, when irradiated under the same conditions described for 13. The tricyclodecenone derivative 19, which was prepared by irradiation of 3,4-dehydro-cu-vetivone (18) in dioxane at 254 nm, was converted exclusively into (h)-dehydro-P-vetivone (20) on irradiation in aqueous acetic acid with >300-nm light. Likewise, 20 was photochemically convertible into 18 via bicyclohexenones 21. Catalytic reduction of 20 gave a 3:l mixture of (&)-p-vetivone (22a) and (&)-lO-epi-&vetivone (22b) in low yield. Lithium-ammonia reduction of 20 gave a 3:7 mixture of 22a and 22b in good yield. The mechanisms of the various photochemical transformations are discussed.
Introduction The generally accepted biogenetic pathways for interconversions of eudesmane, eremophilane (nootkatane), and spiro[4.5]decane sesquiterpenes involve Wagner-Meenvein rearrangements of appropriate carbonium ion intermediates.2 As shown in Scheme I, methyl or methylene migrations in a eudesmane cation can yield the eremophilane or hinesane skeletons, and the corresponding rearrangements in a 4,lO-epieudesmane cation can lead to the nootkatane or spirovetivane ring systems. Several examples of thermal in vitro 1,2-methylmigrations are k n o ~ nand ,~~ one report of a biogenetic-like 1,a-methylenemigration has appeared in the literature.8 (1) This investigation was supported by Public Health Service Research Grant No. GM 15044 from the National Institute of General Medicine and No. CA 12193 from the National Cancer Institute. (2) For a recent review, see: Marshall, J. A.; Brady, S. F.; Andersen, N. H. Fortschr. Chem. Org. Naturst. 1974, 31, 283. (3) (a) For a recent review, see: Coates, R. M. Fortschr. Chem. Org. Naturst. 1976,33,73. (b) Huffman, J. W. J. Org. Chem. 1972,37,2736. (c) Hochstetler, A. R. Ibid. 1974, 39, 1400. (4) (a) Kitagawa, I.; Yamazoe, Y.; Shibuya, H.; Takeda, R.; Takeno, H.; Yosioka, I. Chem. Pharm. Bull. 1974, 22, 2662. (b) Kitagawa, I., Shibuya, H.; Takeno, H.; Nishino, T.; Yosioka, T. Ibid. 1976, 24, 56. (5) Miller, C. A ; Pinder, A. R. J.Chem. SOC.,Chem. Commun. 1977, 230. (6) (a) Caine, D.; Graham, S. L. Tetrahedron Lett. 1976, 2521. (b) Caine, D.; Graham, S. L.; Vora, T. T. J. Org. Chem., following paper in this issue. (7) (a) Buchi, G.; Greuter, F.; Tokoroyama, T. J. Org. Chem. 1962,27, 827. (b) Streith, J.; Pasnelle, P.; Ourisson, G. Bull. SOC.Chim.Fr. 1963, 518. ( c ) Ourisson, G., Proc. Chem. SOC.,London 1964, 274. (8)Hikino, H.; Aota, K.; Kuwano, D.; Takemoto, T. Tetrahedron 1971, 27,4831. (b) We thank Professor Hikino for providing us with copies of the IR and NMR spectra of anhydro-0-rotunol.
Scheme I
eudesmane
4,lO-epieudesmane
\
0 /
spirovetivane (spiro[4.5]decanes)
nootkatane
eremophilane
It is well-known that cross-conjugatedcyclohexadienones having a eudesmane skeleton are converted into guaiane derivatives on irradiation in protic s o l ~ e n t s . ~ ConsidJ~ (9) For reviews, see: (a) Kropp, P. J. Org. Photo. Chem. 1967,1,1. (b) Schaffner, K. Adu. Photochem. 1966, 4, 81. ( c ) Schaffner, K. “Organic Reactions in Steroid Chemistry”; Fried, J., Edwards, J. A., Eds., Van Nostrand-Reinhold: New York, 1972; Vol. 11, pp 33&338.
0022-3263/80/1945-3790$01.00/0 0 1980 American Chemical Society
J. Org. Chem., Vol. 45, No. 19, 1980 3791
Nootkatane and Spirovetivane Sesquiterpenes Scheme I1 R
2
4
3
5
Lo - m I
R
I
I
R=H
0
HO
8
9
I
6
CH,;b, R = H spiro dienone 4a in 52% after chromatography on alumina. eration of the multiple photochemical rearrangements In this run and in subsequently described runs involving exhibited by cross-conjugated dienones in aprotic solventsg other tricyclodecenones, optimum irradiation periods were suggested that interconversions of various sesquiterpene determined by monitoring the course of the reaction by skeletons of the type shown in Scheme I might also be GLC. Irradiations of dienone l a or of tricyclodecenone accomplished photochemically." 2a in anhydrous dioxane using Pyrex-filtered light gave As illustrated in Scheme 11, tricyclodecenones (2) are the some of the desired spiro product 4a. However, GLC primary photoproducts obtained upon irradiation of model analysis indicated that complex mixtures containing sevbicyclic dienones such as 1. These photoproducts are eral other products were produced in addition to 4a. themselves photolabile and undergo further rearrangeIt was felt that steric hindrance to the formation of 5a, ments, presumably via dipolar intermediates such as 3 which would have the two methyl groups on the cyclowhich are considered to arise by electron excitation, propane ring cis to each other, might be an important cleavage of the internal bond of the cyclopropane ring, and factor which accounted for the photostability of 4a comelectron demotion. The dipolar species can undergo 1,2pared with systems that have been previously investigatmethylene migration to yield a spiro dienone 4 or 7,2ed.13 Therefore, the photochemical behavior of the known methyl migration which in the model case would produce ring A unsubstituted tricyclodecenone 2b16 was investithe starting bicyclic dienone 1. The former pathway is gated. Irradiation of 2b under the conditions used for the normally strongly preferred except in complex systems 2a 4a conversion, followed by chromatography of the having structural features which disfavor the production photolysis mixture, gave spiro dienone 4b in 62% yield. of spirocyclic Irradiation of 2b was also carried out in 45% aqueous Spiro dienones derived from 1,2-methinyl migrations in acetic acid, using a quartz probe to house the lamp, prodipolar species analogous to 3 have been obtained by irviding the phenol 917 as the only photoproduct. Since radiation of various steriodal bicyclohexanones in dioxane tricyclodecenones2a and 2b both gave essentially the same with >280-nm ultraviolet light.12 However, it has been results, it appears that the use of long wavelength ultragenerally observed that irradiations of simple tricycloviolet light transmitted via a Pyrex filter for the irradiadecenones with broad-spectrum ultraviolet light lead to tions was the principal factor which allowed the isolation bicyclohexanones related to 6 and/or further rearrangement products such as cross-conjugated dienones (a), of the spiro dienones. Next, the photochemical behavior of various bicyclic phenols (9), and/or linearly conjugated dienones, dedienones with sesquiterpene carbon skeletons was exampending upon the location of substituents and the exact ined. 3,4-Dehydronootkatone ( 10b)18 was prepared by photolysis c o n d i t i o n ~ . ~ J ~ oxidation of nootkatone (lOa)lgwith DDQ and converted Results into the corresponding tricyclodecenone 11 as described Initially, we set out to determine if photolysis conditions above (see Chart I for structures). After irradiation of a could be found which would allow conversion of model solution of 11 in 45% aqueous acetic acid for 30 min using tricyclodecenones such as 2 into the corresponding dienPyrex-filtered ultraviolet light, the starting material had ones (4). Dienone la, which is related to the nootkatane completely disappeared and the spiro trienone 12, the system since it contains a methyl substituent at C-4, was bicyclic trienone 13, and 3,4dehydronootkatone (lob) were prepared by DDQ oxidation14 of the corresponding cisisolated in 46, 37, and 12% yields, respectively, after dimethyl~ctalone'~ and irradiated in anhydrous dioxane chromatography on silica gel. The spiro dienone 12 proved at 254 nm to produce the tricyclodecenone 2a in 62% yield. to be identical with anhydro-@-rotunolwhich has been Irradiation of 2a in 45% aqueous acetic acid using a 450-W obtained from @-rotunolby reaction with phosphorus oxhigh-pressure mercury lamp housed in a Pyrex probe gave ychloride in pyridine.8 Anhydro-@-rotunolwas later shown to be produced as a stress metabolite of blight-infected (10) Piers, E.; Cheng, K. F. Can. J. Chem. 1967,45, 1591; Ibid. 19% potatoes.20 48, 2234. a, R =
-
(11) For a preliminary publication of some of this work, see: Caine, D.; Chu, C.-Y. Tetrahedron Lett. 1974, 703. (12) Frei, J.; Ganter, J.; Kagi, D.; Kocsis, K.; Miljkovic, M.; Siewinski, A.; Wenger, R.; Schaffner, K.; Jeger, 0. Helu. Chim. Acta 1966,49, 1049. (13) (a) Kropp, P. J. J. Am. Chem. SOC.1964,86,4053. (b) Kropp, P. J. Tetrahedron 1965, 21, 2183. (14) Burn,D.; Kirk, R.; Petrow, V. R o c . Chem. SOC.,London 1960, 14. (15) Scanio, C. J. V.; Starett, R. M. J. Am. Chem. SOC. 1971,93,1539.
(16) Bellus, D.; Kearns, D. R.; Schaffner, K. Helu. Chim. Acta 1969, 52, 971. (17) Woodward, R. B.; Singh, T. J. Am. Chem. SOC.1950, 72, 494. (18) Pesaro, M.; Bozzato, G.; Schudel, P. Chem. Commun. 1968,1152. (19) We are grateful to Dr. Charles Varsel of the Coca-Cola Company
for providing us with a generous gift of partially purified nootkatone.
Caine, Chu, and Graham
3792 J. Org. Chem., Vol. 45, No. 19, 1980 Chart I
c
o y p k
0
l o a , 3,4-bond saturated b, 3,4-bond unsaturated
15a, R = H, 3,4bond saturated b, R = H, 3,4bond unsaturated C , R = CH,, 3,4bond saturated
& o
% 0
11
8. 16
I
I
14a, R = H b, R = P-CH,
13
12
CI
18 19
17
20
k
0
21
The structure of bicyclic trienone 13 was established by two independent syntheses. The mixture of octalone derivatives prepared by annelation of (+)-dihydrocarvone with truns-3-penten-2-0ne~~ was oxidized with DDQ to give a 3:7 mixture of the cis trienone 13 and the corresponding trans isomer. A sample of 13 which was >85% pure was collected from this mixture by preparative GLC. A significant quantity of 13 was needed for other work.6 Therefore, a stereospecific synthesis was developed. Dehydrohalogenation of the chloro enone 14a,prepared as described previously,22awith sodium acetate in acetic acid and oxidation of the dienone product (15a)with DDQ in dioxane gave the trienone 15b in 45% overall yield. Selective conjugate addition of lithium dimethylcuprate to the disubstituted, conjugated double bond in 15bB gave a dienone (presumably having trans methyl groups23) which was directly oxidized with DDQ to give the trienone 13 in 60% overall yield. Michael addition of (-)-2-carone to truns-3-penten-2-one was carried out under the conditions previously described with methyl vinyl ketone22 in order to avoid having to introduce the 4-methyl group in a separate step. A 1,5diketone which was converted into chloro enone 14b upon treatment with hydrogen chloride in ethanol was obtained. However, the yield in the Michael addition step was
