422
J. Org. Chem. 1983, 48, 422-425
Oxidation of Enol Silyl Ethers: Preparation of Aeginetolide, Dihydroactinidiolide, and Actinidiolide George M. Rubottom* and Henrik D. Juve, Jr. Department of Chemistry, University of Idaho, Moscow, Idaho 83843
Received July 16, 1982 The preparation of the CI1-terpenic lactones aeginetolide (l),dihydroactinidiolide (Z), and actinidiolide (3) by using 1,3,3-trimethyl-2-(trimethylsiloxy)cyclohexene (9) as a common precursor is discussed. The key steps in the synthetic route involve the sequential m-chloroperbenzoic acid (MCPBA) oxidation and acetylation of 9 and of the siloxy diene 13 derived from 9. Scheme I"
Aeginetolide (l),dihydroactinidiolide (21, and actini-
1
2
4
3
diolide (3) form a series of structurally related, naturally occurring Cll-terpenic lactones. Compound 1 was isolated from Aeginetia indica, a root parasite widely distributed throughout Asia,' while 2 was initially isolated from the essential oil of the leaves of Actinidia polygama.2 Lactone 2 is active, at low level, toward Felidae animals2 and has found use in the perfume industry3 as well as being used as an analeptic agent for the treatment of respiratory depre~sion.~ Since the initial characterization of 2, this compound has also been isolated from several other sources.5-10 Lactone 3 was found also to be a component of Actinidia polygama2 and has been cited for potential use in the perfume industry." Two syntheses of 1have appeared in the literature. The first involved peracid treatment of 4,12 while the second
OSiMe3
0 /
14,R = H
13
5
used the LDA-mediated ring closure of 5.13 In each case,
1
15, R = Ac
bo
d (62Y o 1
f l80%1
1
bo
If
el47%101 (90%I
I
I c
4
0 188 %I
\
0
_
\
3
16
2
(a) LDA/THF, Me,SiCl; (b) MCPBA, Et,NHF, Et,N/Ac,O/DMAF'; ( c ) LTA/CH,Cl,; ( d ) LDA, HOAc/H,O; ( e ) NaOH/H,O/a; ( f ) SOClJpy; ( g ) MeLi, B r z , LiBr/ Li,CO,/DMF/A. a
(1) (a) Dighe, S. S.; Manerikar, S. V.; Kulkarni, A. B. Indian J. chem., Sect. E. 1977, 15B, 546. (b) Dighe, S. S.; Kulkarni, A. B. Zbid. 1974, I2 413. (c) Dighe, S. S.;Kulkarni, A. B. Zbid. 1973, 11, 404. (2) Sakan, T.; Isoe, S.;Hyeon, S. B. Tetrahedron Lett. 1967, 1623. (3) Sakan, T; Isoe, S. Japanese Patent 71 21016; Chem. Abstr. 1971, 75, 98432. (4) Schumacher, J. N. US.Patent 3576008; Chem. Abstr. 1971, 75, 77083. (5) (a) Bailey, W. C., Jr.; Bose, A. K.; Ikeda, R. M.; Newman, R. H.; Secor, H. V.; Varsel, C. J. Org. Chem. 1968, 33, 2819. (b) Kaneko, H.; Ijichi, K. Agric. Biol. Chem. 1968, 32,1337. (6) (a) Bricout, J.; Viani, R.; Miiggler-Chavan, F.; Marion, J. P.; Reymond, D.; Egli, R. H. Helu. Chim. Acta 1967, 50, 1517. (b) Ina, K.; Sakato, Y.; Fukami, H. Tetrahedron Lett. 1968, 2777. (c) Fukushima, S.; Akahori, Y.; Tsuneya, T. Yakugaku Zasshi 1968,88,646. (d) Fukushima, S.;Akahori, Y.; Tsuneya, T. Zbid., 1969, 89, 1729.
(7) Vitzthum, 0. G.; Werkhoff, P.; Ablanque, E. Colloq. Znt. Chim. Cafes Verts, Torrefias Leurs 1975, 7,115; Chem. Abstr. 1976,85,158128. ( 8 ) Moutounet, M.; Dubois, P; Jouret, C. C. R. Acad. Sci. Agric. Fr. 1976,61, 581.
(9) Schreier, P.; Drawert, F.; Junker, A. J. Agric. Food Chem. 1976, 24,331. (IO) Demole, E.; Enggist, P.; Stoll, M. Helu. Chim. Acta 1969,52, 24. (11) Sakan, T.; Isoe, S. Japanese Patent 71 21015; Chem. Abstr. 1971, 75, 98431. (12) Demole, E.; Enggist, P. Helu. Chim.Acta 1968, 51, 481. (13) Goyau, B.; Rouessac, F. Bull. SOC.Chim. Fr. 1978, 590.
1 was then converted into 2. Compound 2 has been the target of a number of synthetic approaches. Dehydration of 1 gives 2,12J3and 4 also affords 2 upon brominationdehydrohalogenation.2 Several groups have taken advantage of the photooxygenation of carotenoids14-17to obtain 2, and the peracid oxidation of p-ionone can also be used.17 Other routes involving the addition of lithium ethoxythe acetylide to 2-hydroxy-2,6,6-trimethylcyclohexanone,18 acid-promoted cyclization of 6,19and the pyrolysis of 75a (14) Isoe, S.; Hyeon, S. B.; Sakan, T. Tetrahedron Lett. 1969, 279. (15) Mousseron-Canet, M.; Mani, J.-C.; Dalle, J.-P. Bull. SOC.Chim. Fr. 1967, 608. (16) Kurata, S.; Kusumi, T.; Iouye, Y.; Kakisawa, H. J. Chem. Soc., Perkin Trans. 1 1976, 532. (17) (a) Isoe, S.; Hyeon, S. B.; Ichikawa, H.; Katsumura, S.; Sakan, T. Tetrahedron Lett. 1968,5561. (b) Takagi, Y.; Kogami, K.; Hayashi, K. Japanese Patent 7569062; Chem. Abstr. 1976, 84,43820. (18) Horii, Z.; Ito, M.; Minami, I.; Yamauchi, M.; Hanaoka, M.; Momose, T. Chem. Pharm. Bull. 1970, 18, 1967.
0022-3263/83/1948-0422$01.50/0 0 1983 American Chemical Society
Oxidation of Enol Silyl Ethers
J. Org. Chem., Vol. 48, No. 4, 1983 423
OH
I
I
S02Ph
7
8
6
have been reported as well. Compound 3 has been prepared via photooxygenation of dehydro @ionone17"by the lithium ethoxyacetylide routela and from 8 by treatment with peracid and then thionyl chloride.12 Our desire to synthesize 1-3 stems from a long-standing interest in developing methods for the preparation of aoxygenated carbonyl compounds from the appropriate enol silyl ethers.20 We felt that the readily available enol silyl ether 9 could be used as the common precursor for the OSiMe3
I
accord with those reported in the literature for the two compounds. The advantage of using 9 in the synthetic plan becomes more clear when the preparation of 3 is considered. The placement of the requisite double bond in 3 up to this point has not been particularly straightforward and/or e f f i ~ i e n t , ' ~ Jand ~ J ~it is not clear that Rouessac's method could be adapted for this purpose. Treatment of 9 with a number of reagents which would be expected to lead to the production of 10 were unsuccessful. Thus the reaction of 9 with Pd(OAc)2/benzoquinone,25Pd(OAc)2/Cu(OAc)z," and DDQ/HMDSZ7and the treatment of the enolate derived from 2,2,6-trimethylcyclohexanonewith PhSeBr followed by H202oxidation2*all led to the formation of mixtures of 10 and 2,2,6-trimethylcyclohexanone.This problem was overcome by reacting 9 sequentially with MeLi then with Br, at low t e m p e r a t ~ r e followed ,~~ by dehydrohalogenation of the resulting bromo ketone with LiBr/LizC03/DMF.30 In this manner, pure 10 was obtained in 84% yield. Enone 10 could also be prepared in
-b OSiMej
9
preparation of all the Cll-terpenic lactones. The following is an account of our investigation into the feasibility of the approach.21p22
Results and Discussion The synthesis of 1-3 is outlined in Scheme I. Enol silyl ether 9 was prepared from 2,2,6-trimethylcyclohexanone in 88% yield. Compound 9 as well as all the other enol silyl ethers mentioned below were obtained by a nonaqueous workup technique that improves the yields for this type of transformation (see Experimental Section). Compound 9 was then converted into 5 by two methods. Treatment of 9 with lead(1V) acetate (LTA)20aor the sequential treatment of 9 with MCPBA and then with AczO/Et3N/DMAPZobgave 5 in yields of 56% and 65%, respectively. Rouessac and Goyau have also prepared 5 by an independent route that was reported while the current studies were underway.13 The LDA-mediated cyclization of 5 finds literature analogy in a study of the cyclization of steroidal a-acetoxy ketones,23and, in fact, this method was employed by Rouessac to obtain aeginetolide (1) in high yield.13 In our hands the reaction afforded 1 in 83% yield. Dehydration of 1 with aqueous sodium hydroxide13or thionyl chloride/pyridine12gives rise to dihydroactinidiolide (2). The structures of both 1 and 2, as shown by spectral and physical proper tie^,^^ are in (19)Torii, S.;Uneyama, K.; Kuyama, M. Tetrahedron Lett. 1976, 1513. (20)(a) Rubottom, G. M.; Gruber, J. M.; Kincaid, K. Synth. Commun. 1976,6,59.(b) Rubottom, G. M; Gruber, J. M. J. Org. Chem. 1978,43, 1599. (c) Rubottom, G. M.; Vazquez, M. A.; Pelegina, D. R. Tetrahedron Lett. 1974,4319. (d) Rubottom, G. M.; Marrero, R. J. Org. Chem. 1975, 40,3783. (e) Rubottom, G. M.; Gruber, J. M.; Mong, G. M. Ibid. 1976, 41,1673. (0 Rubottom, G. M.; Gruber, J. M. Zbid. 1977,42,1052. (9) Rubottom, G. M.; Gruber, J. M.; Boeckman, R. K., Jr.; Ramaiah, M.; Medwid, J. B. Tetrahedron Lett. 1978,4603. (h) Rubottom, G. M.; Mott, R. C.; Juve, H. D., Jr. J. Org. Chem. 1981,46,2717.(i) Rubottom, G. M.; Marrero, R. Syn. Commun. 1981,11,505. (j) Rubottom, G.M.; Gruber, J. M.; Marrero, R. Tetrahedron, in press. (21)For a preliminary report on the synthesis of 1 and 2, see: Rubottom, G. M.; Juve, H. D., Jr. 34th Northwest Regional Meeting of the American Chemical Society, Richland, WA, June 13-15,1979;American Chemical Society: Washington, DC, 1979;Abstract 130. (22)For preliminary report on the synthesis of 3,see: Rubottom, G. M.; Juve, H. D., Jr. 37th Northwest Regional Meeting of the American Chemical Society, Eugene, OR, June 16-18, 1982;American Chemical Society: Washington, DC, 1982;Abstract 101. (23)Bull,J. R.; Tuinman, A. J. Chem. SOC.,Perkin Trans. 1 1976,212.
11
IMeLl,Br2
2 L i B r / L pC03/DMF/A
e
2 Me1 2
12 (68%)
~
10 (85%)
both high yield and purity from enol silyl ether 11 (97% from corresponding ketone) by the bromination-dehydrohalogenation sequence noted above followed by alkylation of 12. In this way a 58% yield of 10 which was 99% pure was obtained. Treatment of 10 with LDA and Me3SiC1gave a 72% yield of 13 which was then oxidized with MCPBA. The resulting a-hydroxy ketone 14 was acetylated (Ac20/ Et3N/DMAP)20bto give a 55% overall yield of the aacetoxy ketone 15. LDA-mediated ring closure of 15 led to the known 1612 (62% yield), which was dehydrated to produce actinidiolide (3) in 80% yield. Compound 3 had spectral characteristics in agreement with those published for the compound.24 Thus all three of the C,,-terpenic lactones 1-3 can be prepared in an efficient, high-yield manner by starting with the readily available enol silyl ether 9. The method would also seem to be general for the formation of lactones from a-acetoxy ketones in those systems where competing enolate formation in the ring-closing step does not interfere.
Experimental Section General Methods. Melting points were determined with a Thomas-Hoover melting point apparatus and are corrected. Proton magnetic resonance ('H NMR) spectra were recorded at 60 MHz on a Varian Anaspect EM 360 spectrometer with Me& using as an internal standard. Carbon magnetic resonance (13C NMR) spectra were recorded at 22.5 MHz on a JEOL FX-9OQ spectrometer with Me4Siusing as an internal standard. Infrared (IR)spectra were obtained on a Perkin-Elmer 621 grating infrared spectrometer, and low-resolutionmass spectra (MS)were obtained on a Hitachi Perkin-Elmer RMU 6 E instrument at 15 eV or on (24)See the Experimental Section. (25)Ito, Y.; Hirao, T.; Saegusa, T. J. Org. Chem. 1978,43,1011. (26)Ito, Y.;Aoyama, H.; Hirao, T.; Mochizuki, A.; Saegusa, T. J. Am. Chem. SOC.1979,101,494. (27)Ryu, I.;Murai, S.; Hatayama, Y.; Sonoda, N. Tetrahedron Lett. 1978,3455. (28)Sharpless, K. B.; Lauer, R. F.; Teranishi, A. Y. J. Am. Chem. SOC. 1973,95,6137. (29)Stotter, P.L.; Hill, K. A. J. Org. Chem. 1973,38,2576. (30)Joly, R.; Warnant, J.; Noming, G.; Bertin, D. Bull. Soc. Chim. Fr. 1958,366.
424
J. Org. Chem., Vol. 48, No. 4, 1983
a Hewlett-Packard 5990A GC/MS at 70 eV. Elemental microanalyses were determined with a Perkin-Elmer Model 240 elemental analyzer. For column chromatography, Woelm silica gel (0.032-0.063mm, ICN Pharmaceuticals GmbH & Co.) was used. All reactions were carried out under a static pressure of 1 atm of nitrogen, and anhydrous magnesium sulfate was employed as a drying agent. 1,3,3-Trimethy l-2-(t rimethy lsiloxy )cyclohexene (9). Compound 9 was prepared by a modification of the methods reported by House and co-workersgland by A i n s w ~ r t h . A ~ ~dry, 250-mL, three-necked, round-bottomed flask that was fitted with a magnetic stir bar, a rubber septum, and a nitrogen gas inlet tube was of freshly charged with 50 mL of dry THF and 4.2mL (38.0"01) distilled diisopropylamine. The reaction vessel was cooled externally to -20"C (dry ice/acetone), and, with stirring, 23.2 mL (37.0mmol) of 1.6 M n-butyllithium (Aldrich) was added slowly by syringe through the septum. Upon completion of the addition, the resulting solution was stirred for an additional 20 min, the cooling bath temperature was lowered to -78"C (dry ice/acetone), was and 4.91 g (35.0mmol) of neat 2,2,6-trimethylcyclohexanone added dropwise through the septum. After 30 min of additional stirring, 9.7 mL (76.0 mmol) of freshly distilled chlorotrimethylsilane (Me3SiC1)was rapidly added to the solution. The mixture was then stirred for 1 h at -78"C and was then allowed to gradually warm to room temperature. The solvent was then removed in vacuo by using a rotary evaportor, and the residue was diluted with 100 mL of dry pentane. The mixture was then filtered and the filtrate concentrated in vacuo to afford crude 9 which was then purified by vacuum distillation. In this manner, 6.5g (88%) of pure 1,3,3-trimethyl-2-(trimethylsiloxy)cohexene (9) was obtained: bp 73-78 "C (4.0mm); IR (neat) 1670 cm-'; 'H NMR (CCJ 6 0.39 (8, 9 H), 1.16 (s, 6 H), 1.58-1.85 (m, 4 H), 1.66 (br s, 3 H), 1.90-2.27 (m, 2 H); MS, m / z (relative intensity) 212 (M+, loo),198 (17),197 (701,156(17),metastables (m*) 183.1, 114.8. Anal. Calcd for C12H210Si: C, 67.85;H, 11.39. Found: C, 68.04;H, 11.53. 2-Acetoxy-2,6,6-trimethylcyclohexanone (5)from the LTA Oxidation of 9. The method cited is essentially that used in ref 20a. A solution of 1.06g (5.0 "01) of 9 in 50 mL of dry methylene chloride was treated with 3.33 g (7.5mmol) of LTA, and the resulting mixture was refluxed for 36 h. The slurry was cooled and filtered, and 1.00 g (6 mmol) of benzyltrimethylammonium fluoride was added to the solution. After 20 h of stirring at room temperature, the reaction mixture was placed in a separatory funnel and was diluted with 150 mL of methylene chloride. The organic solution was then extracted with saturated NaHC03 (2 x 100 mL). The combined aqueous portions were extracted with 50 mL of methylene chloride, and the combined organic portions were dried. filtration followed by removal of solvent in vacuo gave crude 5 which was purified by molecular distillation. In this way, 0.56 g (56%) of pure 2-acetoxy-2,6,6-trimethylcyclohexanone (5) was obtained; bp 60 "C (1.5mm, molecular distillation) [lit.13bp 98-100 'C (16 mm)]. 2-Acetoxy-2,6,6-trimethylcyclohexanone (5) from the MCPBA Oxidation of 9. The method cited is an adaptation of the procedure reported in ref 20b. A solution containing 2.63 g (13.0"01) of 85% m-chloroperbenzoic acid (MCPBA) in 150 mL of dry hexane was stirred at room temperature for 20 min to ensure homogeneity and was then cooled to -15 "C (ice/ methanol). The solution was then treated with 2.29 g (10.8"01) of neat 9 by dropwise addition. The mixture, which was stirred during the course of the addition, was then stirred for an additional 10 min at -15 "C and then for 1 h at room temperature. The resulting slurry was filtered and the solvent removed in vacuo from the filtrate. Addition of a small amount of pentane to the residue followed by fitration and removal of solvent in vacuo from the filtrate gave a clear colorless oil that was dissolved in 150 mL of dry methylene chloride. The resulting solution was treated with 7.85 g (65.0mmol) of triethylammonium fluoride, and this solution was then stirred at room temperature for 10 h. The solution was then transferred to a separatory funnel and se(31) House, H.0.; Czuba, L. J.; Gall,M.; Olmstead, H. D. J. Org. Chem. 1969,34, 2324. (32) Ainsworth, C.; Chen, F.; Kuo, Y. N. J. Organomet. Chem. 1972, 46, 59.
Rubottom and Juve quentially extracted with 50 mL of saturated NaHC03, 50 mL of 1.5 N HCl, and 30 mL of saturated NaHC03 The organic layer was then dried, filtered, and freed of solvent in vacuo to afford the a-hydroxy ketone corresponding to 5. This material was then acetylated as described below without further purification. A solution containing the crude a-hydroxy ketone, 2.2 mL (23 mmol) of acetic anhydride, 10 mg of p-(dimethy1amino)pyridine (DMAP), and 2.25 mL (16.2mmol) of triethylamine was stirred a t room temperature for 24 h. The resulting mixture was then transferred to a separatory funnel and diluted with 75 mL of diethyl ether. The solution was extracted with saturated NaHC03 until gas evolution ceased and then was extracted with 40 mL of water, 40 mL of 1.5 N HC1, and 40 mL of saturated NHC03. Drying, filtration, and removal of solvent in vacuo gave crude 5 which gave, upon vacuum distillation, 1.40 g (65% overall yield from 9) of pure 2-acetoxy-2,6,6-trimethylcyclohexanone ( 5 ) , bp 89-91 OC (5 mm) [Mol3bp 98-100 "C (16 mm)]. Aeginetolide (1). The literature procedure13J3for the preparation of 1 was used to obtain an 83% yield of pure aeginetolide (l), mp 171.5-172 "C (lit.la mp 169-170 "C). The spectral properties of 1 are in agreement with those reported in ref l a and 13. Dihydroactinidiolide (2). The method described in ref 12 was used to obtain a 90% yield of pure dihydroactinidiolide (2), mp 41-42 "C (litOsa mp 42-43 "C). The spectral properties of 2 were in agreement with those reported in ref 5a, 12, and 13. Dehydration of 1 by using 10% NaOHI3 gave 2 mp 42-43 C;47% yield. 2,6,6-Trimethyl-2-cyolohexen-l-one (IO) from Enol Silyl Ether 9. The bromination of 9 was accomplished by using the procedure noted in ref 29. A solution of 1.25g (5.9mmol) of 9 in 25 mL of dry THF was treated at room temperature with stirring with 3.9 mL (7.1mmol) of 1.8 M methyllithium. The resulting solution was then cooled to -78"C (dry ice/acetone), and 1.04g (6.5"01) of bromine was rapidly added. After 1min of stirring, 20 mL of saturated NaHC03 was added rapidly to the reaction mixture. The resulting slurry was extracted with pentane (2x 50 mL), the combined organic extracts were dried and filtered, and solvent was removed in vacuo. The resulting bromo ketone was then dehydrohalogenated by using the procedure given in ref 30. A mixture of crude bromo ketone, 2.27 g (30.0mmol) of lithium carbonate, 1.95g (22.5mmol) of lithium bromide, and 35 mL of dry DMF was heated for 20 h in an oil bath maintained at a temperature between 90 and 100 "C. The resulting mixture was cooled to room temperature and filtered and the filtrate transferred to a separatory funnel. After the addition of 30 mL of 1.5 N HC1, the mixture was extracted with pentane (2x 50 mL). The combined organic extracts were dried and filtered, the solvent was removed in vacuo, and the residue was flash distilled at a pressure of 9 mm to give 0.68 g (84% overall yield) of pure 2,6,6-trimethyl-2-cyclohexen-l-one (10). The physical and spectral properties of this material were identical with those of 10 prepared from 12 (see below). l,3-Dimethyl-2-(trimethylsiloxy)cyclohexene(11). Compound 1 1 was prepared by the method cited above for the preparation of 9. Thus, from 80.0 mmol of diisopropylamine, 150 mL of DME, 76.0 mmol of n-butyllithium, 73.0 mmol of 2,6-dimethylcyclohexanone, and 87.0mmol of Me3SiC1was obtained 13.9g (97%) of pure 1,3-dimethyl-2-(trimethylsiloxy)cyclohexene (11): bp 55-58 "C (4mm); IR (neat) 1680 cm-'; 'H NMR (CDC13) 6 0.09 (s, 9 H), 1.03 (d, 3 H,J = 7 Hz), 1.3-1.7 [m, 7 H,including a br s at 1.55 (vinyl methyl)], 1.7-2.1(m, 3 H);MS, m/t (relative intensity) 198 (M', 39,184(ll),183 (69),169 (19),156 (50),155 (29),141 (28),107 (12),93 (la), 75 (43),73 (loo),55 (21),45 (26), 41 (16).Anal. Calcd for CllHz20Si: C, 66.60;H, 11.18. Found: C, 66.71;H, 11.17. 2,6-Dimethyl-2-cyclohexen-l-one (12). The method given above for the preparation of 10 from 9 was used for the conversion of 1 1 into 12. Thus from 1.98 g (10.0mmol) of 11 in 25 mL of dry THF treated sequentially with 6.1 mL (11.0mmol) of 1.8 M methyllithium and then with 1.76g (11.0mmol) of bromine was obtained the crude bromo ketone. The bromo ketone, in turn, was heated at 90-100 "C (oil bath) for 20 h with a mixture of 1.95 g (22.5mmol) of lithium bromide, 2.27g (30.0mmol) of lithium carbonate, and 35 mL of dry DMF. A workup as described above
J. Org. Chem. 1983,48, 425-432 followed by vacuum distillation of the crude enone gave 0.84 g (12), (68% overall yield) of pure 2,6-dimethyl-2-cyclohexen-l-one bp 72-74 "C (13 mm). The IR, NMR, and mass spectral properties of 12 are in agreement for those reported in ref 33. 2,6,6-Trimethyl-2-cyclohexen-l-one (10) from the Alkylation of 12. The alkylation of 12 was patterned after the procedure given in ref 34. A solution containing 4.5 mL (32.0 mmol) of diisopropylamine, 0.18 mL of HMPA, and 50 mL of dry THF was cooled to -20 "C (dry ice/acetone) and treated with 19.5 mL (31.0 mmol) of 1.6 M n-butyllithium. The resulting solution was cooled to -78 "C and treated with 3.65 g (29.0 mmol) of neat 12, and stirring was continued for 20 min. At this point, 5.6 mL (89.0 mmol) of methyl iodide was slowly added (ca. 5 min), and the resulting mixture stirred for 1 h a t -78 "C. The mixture was then warmed to room temperature, the THF was removed in vacuo, and then the residue was partitioned between 100 mL of diethyl ether and 100 mL of water. The layers were separated, and the aqueous layer was extracted with diethyl ether (2 X 30 mL). The combined etheral layers were dried and filtered, and the solvent was removed in vacuo to give crude 10. Vacuum distillation afforded 3.41 g (85%)of pure 2,6,6-trimethyl-2-cyclohexen-l-one (lo), bp 63-67 "C (12 mm) [lit.35bp 60-65 "C (10 mm)]. The spectral properties (IR, NMR, MS) are in accord with those reported in ref 35 and are identical with those of 10 prepared from the enol silyl ether 9 (see above). 2,6,6-Trimethyl-l-(trimethylsiloxy)-1,3-cyclohexadiene (13). Compund 13 was prepared by the method cited above for the preparation of 9. Thus, from 37.0 mmol of diisopropylamine, 30 mL of DME, 37.0 mmol of n-butyllithium, 30.8 mmol of 10 in 10 mL of DME, and 77.0 mmol of Me3SiC1was obtained, after vacuum distillation, 4.66 g (72%) of pure 2,6,6-trimethyl-l-(trimethylsiloxy)-1,3-cyclohexadiene(13): bp 77-79 "C ( 5 mm); IR (neat) 3035, 1670 (sh), 1658 cm-'; 'H NMR (CClJ 6 0.18 (s, 9 H), 0.87 (s, 6 H), 1.52 (s, 3 H), 1.83-2.10 (m, 2 H), 5.00-5.76 (m, 2 H); MS, m / z (relative intensity) 210 (M', loo), 195 (58), 179 ( 5 ) , metastables (m*) 181.1, 164.3. Anal. Calcd for Cl2HZ20Si: C, 68.50; H, 10.54. Found: C, 68.54; H, 10.51. 2-Acetoxy-2,6,6-trimethyl-3-cyclohexen-l-one (15). Compound 15 was prepared by the method outlined above for the preparation of 5. Thus, from 10.0 mmol of 13, 30 mL of dry hexane, 10.0 mmol of MCPBA, 75 mL of methylene chloride, and 60 mmol of triethylammonium fluoride was obtained crude hydroxy ketone 14. Compound 14 was then acetylated with 21.0 mmol of acetic anhydride, 15.0 mmol of triethylamine, and 0.4 mmol of DMAP to give, after vacuum distillation, 1.08 g (55% (33) Trost, B. M.; Salzmann, T. N.; Hiroi, K. J.Am. Chem. SOC.1976, 98, 4887. (34) Stork, G.; Danheiser, R. L. J. Org. Chem. 1973, 38, 1775. (35) Oppolzer, W.; Sarkar, T.; Mahalanabis, K. K. Helu. Chim. Acta 1976,59, 2012.
425
from 13) of pure 2-acetoxy-2,6,6-trimethyl-3-cyclohexen-l-one (15): bp 70 "C (5 mm, molecular distillation); IR (neat) 3040,1725,1715 cm-'; 'H NMR (CCl,) 6 1.03 (s, 3 H), 1.07 (s, 3 H), 1.30 (s, 3 H), 2.38-2.84 (m, 2 H), 5.29-6.12 (complex m, 2 H); MS, m/z (relative intensity) 196 (M', 8), 153 (33), 126 (47), 98 (14), 93 (15), 84 (59), 71 (E),69 (17), 55 ( l l ) , 43 (loo), 41 (25). Anal. Calcd for CllH1603: C, 67.32; H, 8.22. Found: C, 67.34; H, 8.18. Hydroxy Lactone 16. The hydroxy lactone 16 was prepared by the method cited in ref 23. A solution containing 0.85 mL (6 mmol) of diisopropylamine in 50 mL of dry diethyl ether was cooled to -20 "C (dry icelacetone) and treated with stirring with 3.5 mL (5.5 mmol) of 1.55 M n-butyllithium. After 20 min of stirring, the solution was cooled to -78 "C (dry ice/acetone), and 0.98 g (5.0 mmol) of 15 was added. After 10 min, the reaction mixture was quenched with a solution containing 10 mL of glacial acetic acid in 40 mL of water. The mixture was transferred to a separatory funnel and extracted with chloroform (3 X 30 mL). The combined organic extracts were extracted with saturated NaHC03 ( 5 X 30 mL), dried, and filtered, and the solvent was removed from the filtrate in vacuo to afford a residue that was crystallized from diethyl ether/hexane to give 0.61 g (62%) of pure hydroxy lactone 16 mp 145.5-147 "C (lit.12mp 140-142 "C); IR (Nujol) 3440, 1765, 1745 cm-l; 'H NMR (CDC13)6 1.05 (s, 6 H), 1.52 (s, 3 H), 2.07-2.20 (m, 3 H), 2.39 (d, 1 H, J = 18 Hz), 2.90 (d, 1H, J = 18 Hz),2.68 (br s, 2 H); 13CNMR (CDC13)174.84, 130.27, 126.93, 87.90, 80.87,40.82, 39.15, 36.53, 25.27, 22.53, 20.61 ppm; MS, m/z (relative intensity) 196 (M', 64), 171 (12), 114 (20), 113 (99),112 (24),87 (43),86 (31),85 (loo), metastables (m*) 120.5, 65.5,64.5,44.1,36.6. Anal. Calcd for CllH1603: C, 67.32; H, 8.22. Found: C, 67.10; H, 8.17. The spectral properties of 16 were identical with those of authentic 16 prepared by the method of Demole and Enggist.'* Actinidiolide (3). The dehydration of 16 was carried out according to the procedure given in ref 12. Thus, 0.3 mmol of 16,0.8mmol of thionyl chloride (freshly distilled), and 1 mL of dry pyridine gave, after silica gel chromatography, an 80% yield of pure actinidiolide (3),mp 37-38.5 "C (lit.18mp 38-39 "C). The IR and NMR properties of 3 agree with those reported in ref 12 and 18: MS, m/z (relative intensity) 178 (M', 40) 163 (70), 150 (52), 135 (loo), 111 (22), 107 (24), metastables (m*) 126.4, 121.5.
Acknowledgment. We thank the Research council of the University of Idaho and acknowledge the donors of the Petroleum Research Fund, administered b y the American Chemical Society, for the support of this work. Registry No. 1, 19432-07-6; 2, 15356-74-8; 3, 35035-19-9; 5, 16797-54-9; 9, 83999-44-4; 9 (bromo ketone), 2816-63-9; 10, 20013-73-4; 11, 63547-53-5; 11 (bromo ketone), 55234-03-2; 12, 40790-56-5; 13, 83999-45-5; 14, 83999-46-6; 15, 83999-47-7; 16, 83999-48-8; 2,6-dimethylcyclohexanone,2816-57-1; 2,2,6-trimethylcyclohexanone, 2408-37-9; chlorotrimethylsilane, 75-77-4.
Metal-Catalyzed Organic Photoreactions. Bond-Cleavage Selectivity and Synthetic Application of the Iron(II1) Chloride Catalyzed Photooxidation of Cyclic Olefins' Akira Kohda, Kazuo Nagayoshi, Kazuo Maemoto, and Tadashi Sato* Department of Applied Chemistry, Waseda University, Ookubo 3, Shinjuku-ku, Tokyo 160, Japan Received June 3. 1982 Photooxidation of olefins in pyridine in the presence of iron(II1) chloride produced either a-chloro ketones (type A), gem-dichloro ketones (type B), or a,w-dichloro ketones (type C), depending upon the substitution pattern of the substrate olefin. The synthetic utility of the type B reaction was demonstrated by the synthesis of some natural products. The synthesis of optically active solanone from D-p-menthene confirmed the D configuration of the natural product.
We reported in our previous paper that iron(II1) chloride exhibited a characteristic effect on the photooxidation of
olefins i n pyridine and induced production of either achloro ketone or dichloro ketone as the final product,
0022-3263/83/1948-0425$01.50/00 1983 American Chemical Society
