J. Org. Chem.
3470
1982,47, 3470-3474
H, br s, W1,, = 3 Hz, CHO), 3.03-1.93 (8 H), 2.20 (3 H, s, COCH3), 1.17 (3 H, d, J = 6.6 Hz, Me-lo), 0.86 (3 H, s, Me-5); GC/MS, m/e (relative intensity) 210 (3, M'), 168 (61), 139 (16), 138 (25), 125 (22), 111 (21), 110 (53), 97 (100). Minor diastereomer 3a (lS,5S,lOR): NMR (270 MHz, CDCl,) 6 9.61 (1 H, Br s, Wl = 3 Hz, CHO), 3.02-1.22 (8 H), 2.17 (3 H, s, COCH3),1.16 (3 d, J = 6.6 Hz, Me-lo), 0.96 (3 H, s, Me-5); GC/MS, m l e (relative intensity) 210 (1, M'), 168 (57), 139 (20), 138 (9), 125 (13), 111 (21), 110 (95), 97 (100). Anal. Calcd for ClzH1803(mixture of diastereomers): C, 68.55; H, 8.63. Found: C, 68.27, H, 8.46. Aldol 4. Diketo aldehyde 3 (154 mg, 0.73 mmol) was dissolved in 10 mL of absolute methanol, and 2 mL of 10% aqueous potassium hydroxide was added, while the mixture was allowed to stir for 4 h at 25 "C. The resulting brown solution was cooled in an ice bath and acidified to pH 2 with 37% hydrochloric acid (0.4 mL). The mixture was concentrated in vacuo, and the residue was extracted with ethyl acetate three times. The combined extracts were washed with saturated sodium chloride, dried over anhydrous magnesium sulfate, and concentrated in vacuo to give a crude aldol 4. Purification on a short silica gel column (ethyl acetate) resulted in 143 mg (0.68 mmol, 9 2 % ) of 4 (Rf 0.34) as a colorless oil: NMR (270 MHz, CDCl,) 6 4.46 (1 H, br s, OH), 4.00 (1H, tdd, J = 11.2,4.4, 2.6 Hz, H-7), 3.01 (1 H, dd, J = 11.2, 10.0 Hz, H-8), 2.61 (1H, dt, J = 10.0, 2.6 Hz, H-8), 2.59-1.32 (8 H), 1.22 (3 H, d, J = 7.0 Hz, Me-lo), 0.78 (3 H, s, Me-5);IR (neat) 3460 (OH), 1739,1700 cm-'; MS, m / e (relative intensity) 210 (79, M'), 192 (14), 97 (100).
A,
Anal. Calcd for C12H1803: C, 68.54; H, 8.63. Found C, 68.74; H, 8.72.
Acknowledgment. This work was supported by the National Institutes of Health (Grant No. CA-16432). The author is grateful to Professor Frederick E. Ziegler for his enlightening suggestions and t o Mr. P. Damou for recording high-field NMR spectra (NSF Northeast Regional NMR Facility, Department of Chemistry, Yale University). Registry No. (1)-1, 74645-43-5; (1)-2, 60426-81-5; (1)-3a, 76156-83-7;(1)-3b, 81939-03-9;(1)-4,81875-17-4;5,34780-08-0;6a, 609-02-9;6b, 609-08-5;6c, 56834-42-5;7a, 69027-55-0;7b, 66446-63-7; 8a, 81875-18-5; 8b, 81875-19-6; 8c, 81875-20-9; 8d, 81875-21-0; 8e, 81875-22-1; (f)-cis-S (isomer l), 81875-23-2; (i)-cis-S (isomer 2), 81939-04-0; (1)-trans-9 (isomer l),81939-05-1; (i)-trans-g (isomer 2), 81939-06-2; (f)-cis-lO (isomer l),81875-24-3; (f)-cis-lO (isomer 2), 81939-07-3; (1)-trans-10 (isomer l ) , 81939-08-4; (f)-trans-lO (isomer 2), 81939-09-5; (1)-11, 81875-25-4; 12, 81875-26-5; 13, 81875-27-6; 14, 81875-28-7; 15b, 81875-29-8; (1)-16 (isomer l), 81875-30-1; (1)-16 (isomer 2), 81939-10-8; (1)-17 (isomer l),8187531-2; (1)-17 (isomer 2), 81939-11-9; (1)-18 (isomer l), 81875-32-3; (*)-lS (isomer 2), 81939-12-0; (*)-19 (isomer l),81875-33-4; (1)-19 (isomer 2), 81939-13-1; 20, 81875-34-5; 21, 81875-35-6; ethyl propionate copper salt, 81875-36-7; ethyl propionate, 105-37-3; ethyl propionate lithium enolate, 81355-01-3; allyl bromide, 106-95-6; 2methyl-2-cyclopentenone,1120-73-6;ethyl 2 4 l-hydroxy-2-methyl-2cyclopenten-1-yl)propanoate,81875-37-8.
Synthesis of the DZd-DinoradamantaneDerivatives Having Two Coaxially Oriented Unsaturated Centers. 6-Methylene-DZd-dinoradamantan-2-one and D 2d-Dinoradamantane-2,6-dione Masao Nakazaki,* Koichiro Naemura, Hiroshi Harada, and Hideya Narutaki Department of Chemistry, Faculty of Engineering Science, Osaka University, Toyonaka, Osaka 560, Japan Received February 2, 1982
From the cyclopentadienemaleic anhydride adduct was prepared the norbornenecarboxylic acid 22. Treatment of the acid chloride 23 with triethylamine afforded the tetracyclic ketone 24 which was converted into the dinoradamantanecarboxylic acid 25 by a basic ring-opening reaction. The sequence of conversions involving the Cope elimination of the amine oxide derived from the amine 31 provided 6-methylene-Dwdinoradamantan-2-one (6) whose Os04-NaI04 oxidation eventually yielded DZd-dinoradamantane-2,6-dione (7) of Dzsymmetry. Bridging the 1,4 and 2,5 positions with CH2or CH2CH2 groups freezes cyclohexane's conformational mobility t o make it assume a twist-boat conformation confined in the resulting tricyclic cage-shaped molecules. Twistane (1) of D,symmetry and twist-brendane (2) of C2 symmetry can be cited as examples (Chart I). They are both chiral, and their preparation in optically active modifications and determination of their absolute configuration have been reported from our laboratory.' Bridging these positions with two CH2 groups, however, provides a n achiral tricyclic compound, DZd-dinoradamantane (3), because introduction these CH, groups eventually creates another twist-boat cyclohexane moiety of opposite chirality interlocked with the original one. Since four C H 2 groups in D,d-dinoradamantane (3) are a pair of enantiotopic molecular subunits, conversion of one (1) Adachi, K.; Naemura, K.; Nakazaki, M. Tetrahedron Lett. 1968, Tichg, M. Ibid. 1972,2001. Tichg, M.; Sicher, J. Collect. Czech. Chem. Commun. 1972, 37, 3106. Naemura, K.; Nakazaki, M. Bull. Chem. SOC. Jpn. 1973, 46, 888. Nakazaki, M.; Naemura, K.; Harita, S. Ibid. 1976, 48, 1907. 5467. Tichg, M.; Sicher, J. Ibid. 1969, 4609.
chart I X
X
of these CH2 groups into carbonyl group desymmetrizes t h e D2d symmetry inherent t o 3, leading t o formation of DZd-dinoradamantan-2-one (4) of C, symmetry. After having established the absolute configuration2 of this interesting cage-shaped compound 4, in which four among eight carbon atoms are asymmetric, we carried out its microbial3 a n d horse liver alcohol dehydrogenase (2) Nakazaki, M.; Naemura, K.; Arashiba, N. J. Chem. Soc., Chem. Commun. 1976, 678. Nakazaki, M.; Naemura, K.; Arashiba, N. J. Org. Chem. 1978,43, 888.
0022-326318211947-3470$01.25/00 1982 American Chemical Society
J. Org. Chem., Vol. 47, No. 18, 1982
D2d-DinoradamantaneDerivatives
Scheme I11
Scheme I h 2 ; 2
11
8 R=H 9 R=CI
10
16 X=OH 20 X=OTs 21 X=CN 2 2 X=CO2H 23 X=COCI
-
0&H2-
24
Scheme I1
27 R=OMe 14 R=NMe2
17
28 R = O H 29 R = C I 30 R= NMe2
18
19
(HLADH)4mediated oxidoreduction to disclose that although this gyrochiral ketone 4 is peculiar in its reluctance toward these biological systems, both the microbial PC2-ketone rule and the HLADH M-Cz-ketone rule are successfully applicable to predict the stereochemistry of its metabolites. In the course of these investigations, we happened to notice that 4-methy1ene-Dzd-dinoradamantan-2-one (5) exhibits a A,, (isooctane) of 300.5 nm (t 445) in its UV spectrum, suggesting an unusually strong homoconjugation. This coupled with a suggestion made from Professor J. Bernstein, Ben-Gurion University of the Negev, prompted us to prepare its gyrochiral regioisomers, 6-methyleneD2d-dinoradamantan-2-one(6) (C2 symmetry) and DZddinoradamantane-2,6-dione(7) (D2symmetry), both with the unsaturated centers coaxially oriented along their C2 axes, and to study their electron spectra as well as their microbiological transformation^.^
Results and Discussion There have been reported two feasible synthetic routes to the Dxdinoradamantane molecular framework (Scheme I), one (a)6involving the Paterno-Biichi photocyclization of the unsaturated aldehyde 8 to the oxetane 10 and the other (b)' involving intramolecular cyclization of the ketene intermediate generated from the unsaturated acid chloride 9.
As for the functional group which could be transformed
into a carbonyl group in a later stage of the synthetic route, our choice was an exocyclic methylene group (X = CHz, Scheme I), and this strategy required 17 and 23 as our primary synthetic targets. Synthetic Approach Involving the Paterno-Buchi Photocyclization (Scheme 11). The half-ester 12 obtained from the cyclopentadiene-maleic anhydride adduct (3) Nakazaki, M.; Chikamatau, H.; Naemura, K.; Nishino, M.; Murakami, H.; Asao, M. J . Org. Chem. 1979, 44, 4588. (4)Nakazaki, M.; Chikamatau, H.; Naemura, K.; Suzuki, T.; Iwasaki, M.; Sasaki, Y.; Fujii, T. J. Og. Chem. 1981, 46, 2726. (5) We have reported microbial stereodifferentiating reduction of both 2,6-adamantanedione and hexahydrodibenzoheptene-5,ll-dione with two carbonyl groups coaxially oriented along the C2axis: Nakazaki, M.; Chikamatau, H.; Nishino, M.; Murakami, H. J.Org.Chem. 1981,46, 1151. (6) (a) Sauers, R. R.; Shinski, W.; Mason, M. M. Tetrahedron Lett. 1969, 79; (b) Sauers, R. R.; Kelly, K. W.; Sickles, B. R. J. Org.Chem. 1972,37, 537. Sauers, R. R.; Schinski, W.; Mason, M. M.; O'Hara, E.; Byme, B. Ibid. 1973, 38, 642. (7) Sauers, R. R.; Kelly, K. W. J. Org. Chem. 1970, 35, 3286.
31
3471
+ CH2 25 R = O H 26 R=OMe
32 X=CH2 Y=
