Synthesis and Stereochemistry of Tetramethyldecahydroanthracene

Aust. J. Chem., 1989,4 2 , 511-25

Synthesis and Stereochemistry of Tetramethyldecahydroanthracene Derivatives

Douglas J. Bvecknell, Raymond M. Carman a n d Russell C. Schumann Department of Chemistry, University of Queensland, St. Lucia, Qld. 4067.

Abstract A series of tetramethyldecahydroanthracene

derivatives have been synthesized from Their the Diels-Alder product from 2,3-dimethylbuta-1,3-dieneand p-benzoquinone. stereochemistry, conformational properties and n.m.r. spectra are discussed.

Introduction In connection with a study1 of the geometry of complexation of lanthanide shift reagents with carbonyl compounds, we required a symmetrical conformationally rigid ketone containing substituents which were located at wide angles from the carbonyl bond axis, and which would give clearly defined 1~ and 13c n.m.r. signals. The tetramethyloctahydroanthracen-9(1H)-one(1) was selected a s a suitable compound. In the course of synthesizing ketone (11, we have prepared a number of tetramethyldecahydroanthracene derivatives, and have studied their stereochemistry and conformational properties. In principle, the synthesis of the ketone (1) simply involves the reaction of two equivalents of 2,3-dimethylbuta-1,3-dienewith benzoquinone followed by epimerization at the ring junctions to give the required all-trans stereochemistry, and removal of one of the carbonyl groups. The Diels-Alder reaction between benzoquinone and unsubstituted butadiene was originally believed2s3 to involve addition of the two diene molecules to the same face of the quinone, but it is now k n o ~ n that ~ , ~the two diene molecules add to opposite faces of the benzoquinone ring, to produce the stereochemistry shown in structure ( 2 ) . This compound was readily isomerized on treatment with base to the all-trans isomer (3).335,6 In a similar set of reactions, 2,3-dimethylbuta-1,3-dienereacted with benzoquinone to give the tetramethyl derivative2 which should therefore have structure (4), and this compound also isomerized2 on treatment with base to give a product which presumably had stereochemistry (5). l

Brecknell, D. J., Carman, R. M., and Schumann, R. C., unpublished data. organ, G. T., and Coulson, E. A., J. Chem. Soc., 1931, 2323. Alder, K., and Stein, G., Justus Liebigs Ann. Chem., 1933,501, 247. Crossley, N. S., and Henbest, H. B., J. Chem. Soc., 1960,4413. Hill, R. K., Martin, J. G., and Stouch, W.H., J. Am. Chem. Soc., 1961,83, 4006. Parker, W. L., and Woodward, R. B., J. Org. Chem., 1969, 34, 3085.

D. J. Brecknell, R. M. Carman and R. C. Schumann

The removal of one of the carbonyl groups from the isomerized butadiene adduct (3) has been achieved6 by reduction to the hydroxy ketones (6) with tri-t-butoxyaluminium hydride, followed by reduction of the mesylates (7), and oxidation of the resulting alcohols (8).

Results and Discussion Application of the procedures described above to the synthesis of the target ketone (1) from diketone (5) was complicated by the gross insolubility of the diketone (5) in virtually all common organic solvents. Attempted partial reduction with a variety of reducing agents and solvents failed to produce usable amounts of the hydroxy ketones (9), giving instead a mixture containing substantial amounts of diols (10) and ( l l ) , as well as starting material (5). The rate of reduction of the insoluble dione (5) is apparently restricted by the rate at which the compound dissolves, while the more soluble hydroxy ketones (9) produced by this initial reduction are readily reduced further. An alternative route to the ketone (I), based on the removal of one of the hydroxy groups of the diols (10) and (111, was more successful. Reduction of the diketone ( 5 ) with an excess of sodium borohydride gave a mixture of the two diols (10) and (11) in the ratio 5 7 : 43. This mixture of diols was also very insoluble in many organic solvents, and could not be separated by chromatography or fractional crystallization. However, the corresponding acetates (12) and (13) were separable by chromatography, and the pure diols were then obtained by hydrolysis.

Tetramethyldecahydroanthracene Derivatives

The structures of the diols followed from their n.m.r. spectra (Tables 1-3). The major diol showed ten 13c n.m.r. lines, and was therefore assigned the C, cis-diol structure (10); the coupling constants for H9 and H 10 confirmed the cis arrangement of the hydroxy groups. The minor isomer showed only five 13C n.m.r. lines, and was therefore one of the C2h trans-diols (11) or (14). The splitting pattern for H9 and H 10 in this minor isomer revealed that both hydroxy groups were equatorial, and the compound was therefore assigned structure (11). None of the trans-diaxial isomer (14) was detected, even though reduction of the related diketone (3) was reported7 to produce a mixture of the diequatorial, equatorial-axial and diaxial diols in the ratio 4 : 4 : 1.

(20)

Scheme 1

The 13cn.m.r. spectra of diols (10) and (11) also confirmed the stereochemistry of diketone (5). The n.m.r. spectra of compound (5) do not clearly differentiate it from structure (15) because of the symmetry of the two diketones, and because, in each structure, the hydrogens at the ring junctions are expected to show similar coupling patterns. However, reduction of diketone (15) can produce only two diols, each having no greater than C2 symmetry, and therefore showing at least ten lines in the 13c n.m.r. spectrum. Reduction of diketone (5), on the other hand, can produce three diols, compounds (10) (C, symmetry, ten 1 3 n.m.r. ~ lines), (11) and (14) (both C2h symmetry, five lines). The isolation of a diol with five 13C n.m.r. lines therefore indicates that the diketone must have structure (5). Hill, R. K., and Ladner, D. W.,Tetrahedron Lett., 1975, 989.

A

Me

H leq,8eq

H lax,8ax

H4eq,5eq

'H n.m.r. chemical shifts (6) in CDC13 H4ax,5ax H4a,lOa H8a,9a H9eq H9ax

H lOeq

H lOax

Others

2.11, acetate Me; 2.13, acetate Me 2.05, acetate Me 2.43, tosylate Me; 7 32, I-I 3', H 5'; 7.79, H 2', H 6' 2.43, tosylate Me; 7.31, H3', H5'; 7 - 8 0 , H2', H6' 2 - 32, tosylate Me; 7.34, H 3', H 5'; 8 . 0 1 , H2', H6'

Table 1. 'H n.m.r. chemical shifts for 4aa,Sa&9a&IOaa-octa-and deca-hydroanthracene derivatives

The first value assigned to the 2-Me and 7-Me groups, the second value to the 3-Me and 6-Me groups. From extrapolation of E ~ ( f o d ) ~ - i n d u c eshift d data. Spectrum recorded in (Ds)pyridine at 90". Obscured in multiplet at 6 1-74-2 -00. May be interchanged.

Compound


The removal of one of the hydroxyl groups from each of these diols was achieved by lithium aluminium hydride reduction of their monotosylates, although the tosylation reaction did not proceed cleanly. Treatment of the crude mixture of diols ( 1 0 ) and ( 1 1 ) with p-toluenesulfonyl chloride produced a mixture containing the hydroxy tosylates ( 1 6 ) and ( 1 7 ) and the ditosylate ( 1 8 ) , together with the chlorides ( 1 9 ) , ( 2 0 ) and ( 2 1 ) . A possible set of reactions for the production of these various products is given in Scheme 1. The formation of chlorides a s side-products in the tosylation of alcohols with p-toluenesulfonyl chloride has been previously r e p ~ r t e d and , ~ has been ascribed to nucleophilic displacement by chloride ion on the initially formed tosylates. This view was confirmed by treatment of the hydroxy tosylate ( 1 7 ) with ammonium chloride and lithium chloride in warm pyridine, to produce the chloride ( 2 1 ) . On the other hand, the ditosylate ( 1 8 ) failed to produce any detectable amounts of chlorides ( 1 9 ) and ( 2 0 ) . This lack of reaction may simply be due to the extreme insolubility of the ditosylate ( 1 8 ) in pyridine, even when heated. The formation of the dichloride ( 2 0 ) may then best be explained by conversion of the hydroxy tosylate ( 1 6 ) into the chloro alcohol ( 2 2 ) , which then undergoes further tosylation and substitution by chloride ion. All of the isolated products from this reaction mixture involved tosylation of only equatovial hydroxyl groups; no products from the tosylation of axial hydroxyl groups (with possible further S N 2 substitution to equatorial chlorides) were d e t e ~ t e d . ~ Table 2. Coupling constants for 4aa,8a/3,9a&lOaa-octa- and deca-hydroanthracene derivatives Cornpound

A

4a,9a

leq,9a

lax,9a

4a,4eq

Coupling constants (Hz) 4a,4ax 4a,lOeq 4a,lOax

9a,9eq

9a,9ax

lOeq,lOax

May be interchanged.

Reduction of the hydroxy tosylates ( 1 6 ) and ( 1 7 ) with lithium aluminium hydride produced the alcohols ( 2 3 ) and ( 2 4 ) respectively. Oxidation of either of these alcohols, with pyridinium chlorochromate, gave the ketone ( 1 ) as the only product. In subsequent preparative runs, the product mixture from the tosylation reaction was reduced directly with lithium aluminium hydride, leading to a mixture of only three products-the alcohols ( 2 3 ) and ( 2 4 ) and hydrocarbon ( 2 5 ) . Oxidation of this mixture gave the required ketone ( 1 ) and hydrocarbon ( 2 5 ) , which were readily separated. Blickenstaff, R. T., and Chang, F. C., J. Am. Chem. Soc., 1958, 80, 2726. Fieser, L. F., and Fieser, M., 'Steroids' p. 216 (Reinhold: New York 1959).

C5 Cs

Cs

C2h

(24)

(25)

'

3-Me 6-Me

18.83

18.77, 18.97

34.65, 3 5 - 9 7 33.35, 35.14 35.76, 36.13, 39-40,45.48 30.73, 34.24, 39.86,43.49 38.54, 39 - 79

C1, C8 C4, C5 C4a, C10a C8a, C9a

40.08

41 . 0 9 40.08

71.86

71.05 71.37' 81.46

125-08

124.43, 125.06

123.52 123.92, 123.97 124.50, 124.82

n.m.r. chemical shifts (6) in CDCI, C 10 C9 C2. C 7 C3, C6

71.05 70. 97B 40.05

'" Others

20.95. 21 -05, acetate. methyls 171 -08. 171.18, acetate carhonyls 21 -03, acetate methyls 171 .18, acetate carbonyls 21.55, tosylate Me; 127.76, 129.44. 135.36, 144.29, aromatics 21 - 55, tosylate Me; 127.68, 129.39, 135.56, 144.11, aromatics 21 - 32, tosylate methyls 128.33, 130-14, 136.59, 145 -00, aromatics

'kn.m.r. chemical shifts for 4aa,8a&9a&10aor-octa-and deca-hydroanthracenes

18.80 18.83, 18.90 18.76, 18.89

2-Me 7-Me

Table 3.

Spectrum recorded in (Ds)pyridine at 90". May be interchanged.

C2h

(20) (21) (23)

A

Symmetry

Compound


An alternative route for the synthesis of the ketone (1) was also investigated (Scheme 2). Partial reduction of the diketone (4) was expected to give the hydroxy ketone (26), which would be epimerized by base to the stereoisomers (27) and (28), each containing one cis- and one trans-fused ring junction. Removal of the carbonyl group (e.g., Wolff-Kishner reduction), and oxidation of the resulting alcohols (29) and (30) would then give ketone (31), to be e ~ i m e r i z e dto the required ketone (1).

w H

H

-*+* base

L

H

H

OH

OH

(1)

Scheme 2

H

H OH

(31)

In contrast to the attempted partial reduction of diketone (S), the somewhat more soluble diketone (4) was readily reduced to the hydroxy ketone (26) by brief treatment with sodium borohydride. The base-catalysed epimerization of hydroxy ketone (26) gave a mixture of four hydroxy ketones, the major components of which were the required isomers (27) and (28), but Wolff-Kishner reduction of the resulting mixture of isomers gave a mixture of four alcohols, in which the desired isomers (29) and (30) were only minor components which could not be satisfactorily separated from the major components (32) and (33). These reactions are discussed in detail in a separate report.1° lo

Brecknell, D. J., Carman, R. M., and Schumann, R. C., Aust. J. Chem., 1989, 4 2 , 527.


When the reduction of diketone (4) with sodium borohydride was allowed to proceed to completion, a mixture of two diols in the ratio 75 : 25 was produced. Oxidation of each of these diols led to the original diketone (4), establishing the unchanged stereochemistry of their carbon skeletons. Significant broadening was observed in the room-temperature 13C n.m.r. spectra of the major diol and of the diacetate of the very insoluble minor isomer, indicating that both compounds involve conformational exchange. Sharp, slow-exchange spectra could be obtained at -50"; the major isomer now showed eighteen lines, consistent with structure (34) (C1 symmetry in any individual conformer), while the diacetate of the minor isomer showed only eleven lines, corresponding to the diacetate (35) of the major (diequatorial) conformer of the trans isomer (36), which exhibits S2 symmetry. The coupling constants in the slow-exchange 'H n.m.r. spectra confirmed the presence of one axial and one equatorial hydroxyl group in the major isomer (34), and of two equatorial hydroxyl groups in the minor isomer (36).

Borohydride reduction of the related dione (37) has also been reported to give cis-diol (38) as the predominant p r o d u ~ t . ~ N.M.R. Assignments for Ketone ( I ) A complete assignment of the lH and 13C n.m.r. spectra for ketone (1) in deuterochloroform, required for the lanthanide-induced shift study,' was obtained with the aid of homo- and hetero-nuclear correlation experiments and lanthanide shift reagents. (i) lH assignments (Table I).-One-proton multiplets at 6 1 . 2 6 and 1 . 9 5 , and a two-proton multiplet at 6 1 . 7 0 could be assigned to H loax, H lOeq and H4a+H lOa respectively, on the basis of their chemical shifts and coupling patterns. A homonuclear ( l H-' H) chemical shift correlation (cosy) experiment enabled location of signals for H 8a+H 9a (6 2.22) and the methylene hydrogens attached to C4,C 5 (6 1 . 9 1 , 2 - 0 5 ) and C 1,C8 (6 2 . 0 2 , 2.26). The axial and equatorial C 4,C 5 hydrogens were then differentiated by their coupling patterns. The remaining assignments were made with the aid of lanthanide shift


reagents. The overlapping signals due to the C 1,C8 hydrogens were separated by careful addition of Eu(fod)3 to the n.m.r. sample, and the coupling patterns then allowed assignment of the peaks. On successive additions of Eu(fod)3, the methyl signal at 6 1 . 6 4 moved slowly upfield, while the methyl signal at 6 1 . 6 0 moved more rapidly downfield. The value of the lanthanide-induced shift is given by the McConnell-Robertson equation:ll

where 0 is the angle between the principal magnetic axis of the LSR-substrate complex (usually taken as coincident with the lanthanide-donor bond) and the vector joining the lanthanide ion and the observed nucleus. For Eu(fod)3, upfield (negative) induced shifts require values of 0 > 5 5 " , and so the signal at 6 1 * 64 was assigned to the C 2,C 7 methyl groups, which must have a greater value for 0 than do the C3,C6 methyls. The chemical shifts for H leq,8eq and H4ax,5ax (partly obscured) were determined by extrapolation of Eu(fod)3-shift data to zero lanthanide concentration. (ii) 13cassignments (Table 3).-With the complete assignment of the I H spectrum available, the assignment of the 13C n.m.r. spectrum followed from ) shift correlation experiment. The only a heteronuclear ( 1 3 c - l ~chemical assignments not possible from these results were those of the olefinic carbons, which exhibit no correlations. Addition of Yb(fod)3 to the n.m.r. sample caused a larger downfield shift for the signal at 6 1 2 4 . 7 1 than for the signal at 6 123.82. The former signal was therefore assigned to C 2 and C 7, which are closer to the complexation site than C3 and C6, and so should experience a larger induced shift.

Conformational Isomerism Decahydroanthracene derivatives containing two cis-fused ring-junctions can undergo conformational inversion involving the two chair conformations of the central ring.12 The conformational mobility of such compounds described above was evident from their n.m.r. spectra. In compounds containing one or two carbonyl groups in the central ring, this mobility was revealed by the observation of averaged n.m.r. spectra. The presence of an sp2 centre in the inverting ring lowers the activation energy for this process,13 which is therefore rapid at room temperature, and the resulting spectrum appears as an average of the spectra for the two conformations. For the hydroxy ketone (26), this averaging was seen in the coupling constants for H 10 (geminal with the hydroxyl group), which were atypical for normal axial or equatorial hydrogens in these systems, and showed that compound (26) is a mixture of rapidly interconverting conformers (26ax) and (26eq).1° l1

McConnell, H. M., and Robertson, R. E., J. Chem. Phys., 1958, 29, 1361. M. A., van de Graaf, B., and Vanhee, P., Recl Trav. Chim. Pays-Bas,

a Tavernier, D., Bass, J.

1983, 102, 352. Lack, R. E., Ganter, C., and Roberts, .I.D., J. Am. Chem. Soc., 1968, 90, 7001.

l3


Table 4. Com- T pound (K)

A

" '

13cn.m.r. chemical

2-Me, 3-Me,

shifts for 4aa,8*,9aa,lOa@octa- and decahydroanthracene derivatives

13C n.m.r, chemical shifts (6) in CDC13 C 1, C4, C 5 , C8, C4a, C9 C10 C2, C 3 , C6, C7A

AcetateB

Individual resonances not assigned. Values are for acetate methyl and acetate carbonyl respectively. At ambient temperature. Very broad. Broad. Spectrum recorded in (Djlpyridine. All broad.

For compounds containing only sp3-hybridized carbons in the central ring, the conformational interconversion was usually sufficiently slow at room temperature to produce considerable broadening in both lH and 13c n.m.r. spectra. The diol (34) and the diacetate (35) both showed n.m.r. spectral broadening at room temperature, but at 90" gave sharp 13c n.m.r. spectra (Table 4), containing nine and eleven lines respectively, while at -SO0, they again gave sharp spectra, now showing eighteen and eleven lines respectively. In the case of the trans diacetate (35), each conformer has S2 symmetry, and therefore exhibits eleven 13C n.m.r. signals under conditions of slow exchange, but the spectrum due to the less stable diaxial conformer is too weak to be observed. Conformational inversion of the C 1 cis isomer (34) produces the enantiomeric conformer, and under conditions of slow exchange the spectrum shows a single set of eighteen lines which average in pairs to nine lines at higher temperatures. The free energy of activation for the inversion of the cis-diol (34) was determined from the coalescence temperature T c for exchanging signals, and their chemical shift difference Av, by using the equation (2):


which was derived from Gutowsky and Holm's expression for the rate of exchange,14 and the Eyring equation,15 a transmission coefficient K = 0 . 5 being used to account for equal probabilities of formation of the enantiomeric conformers from the transition state. A value of 5 1 . 5 kJ mol-l was obtained from the coalescence temperature (258 K) of a pair of 13C methyl signals. The value for A G : ~ of~ 51.5 kJ mol-I in diol (34) can be compared with that reported for the inversion of hydrocarbon (39) ( A G : ~ 4~7 . 9 kJ mol-I),12 which suggests that the methyl groups in diol (34) do not significantly affect the energy barrier for inversion. The difference of 3 . 6 kJ mol-I is similar to the difference of 3 . 4 kJ mol-I reported for the inversion of diol (40) ( A G : ~ ~ 4 4 . 8 kJ mol-1)16 relative to that of hydrocarbon (41) (AGio2 4 1 . 4 kJ mol-I).17 The higher barrier to inversion of diol (40) in this pair of compounds was attributedL6 to an adverse interaction between one of the oxygen atoms and an allylic hydrogen in the transition state.

Experimental ' H (400 MHz), 13c (100.54 MHz) and two-dimensional n.m.r. spectra were recorded on a Jeol JNM-GX 400 spectrometer. Spectra were recorded with tetramethylsilane a s internal reference (6 0 . 0 0 ppm) in CDCI3, unless otherwise indicated. 'H n.m.r. spectra were recorded by using 32x21° data points over a bandwidth of 4000 Hz (digital resolution of 0 . 2 4 Hz). 13cn.m.r. spectra were recorded by using 64x21° data points over a maximum bandwidth of 24000 Hz (minimum digital resolution of 0 . 7 3 Hz). Homonuclear correlation experiments (cosy 90) were carried out by using a spectral width of 620 Hz in each domain (6 = 1-2.5). A 256 by 1024 data matrix was collected. 32 transients with a recycle time of 3 s were acquired for each of the 256 time increments. The matrix was zero-filled in both dimensions and multiplied by a sine-bell function before transformation. After transformation the matrix was symmetrized. Heteronuclear correlation experiments were performed by using a spectral width of 620 Hz in the F1 domain ('H 6 1-2.5), and 3900 Hz in the F2 domain (13C 6 = 17-56). A 128 by 1024 data matrix was collected. 196 transients with a recycle time of 2 . 5 s were acquired for each of the 128 time increments. Fixed delays A1 (1/2J) and A2 (1/4J) were set for J 139 Hz. Both dimensions were zero-filled and multiplied by a sine-bell function before transformation. Variable-temperature 'H and 13C n.m.r. spectra were recorded as CDC13 solutions (about 1 0 mg ml-I) in a 5-mm n.m.r. sample tube with tetramethylsilane as the internal reference. The settings of the variable temperature unit were checked against a 'methanol n.m.r. thermometer'.'" Some 'H coupling constants were obtained by comparison of experimental and computergenerated coupling patterns.

-

Gutowsky, H. S., and Holm, C. H., J. Chem. Phys., 1956, 2 5 , 1228. Eyring, H., Chem. Rev., 1935, 17, 65. l6 Vanhee, P., and Tavernier, D., Bull. Soc. Chirn. Belg., 1983, 9 2 , 767. l 7 Vanhee, P., and Tavernier, D., Bull. Soc. Chim. Belg., 1981, 90, 697. l 8 Van Geet, A. L., Anal. Chem., 1970, 4 2 , 679. l4 l5


Analytical gas chromatography was performed on 25-m BPI ( 0 . 2 mm i.d.1 and 25-m BPS ( 0 . 2 mm i.d.) capillary columns in a Hewlett-Packard 5890 gas chromatograph equipped with a flame ionization detector and nitrogen carrier gas. Retention times and peak areas were determined by a Hewlett-Packard 3992 electronic integrator. Gas chromatographic-mass spectral data were obtained upon a Hewlett-Packard 5992B instrument equipped with a 25-m BPS ( 0 . 2 mm i.d.) capillary column, helium carrier gas and electron impact ionization at 70 eV being used. Some low-resolution and all high-resolution mass spectra were recorded on a Kratos MS25 RFA spectrometer, at 70 eV unless otherwise stated. Infrared spectra were recorded in the range 4000-400 cm-I on a Perkin Elmer 397 grating spectrometer and are calibrated against a polystyrene standard. Microanalyses were performed upon a Carlo Erba 720 Autoanalyser. Melting points are uncorrected. Diketone (4)

2,3-Dimethylbuta-1,3-diene (52.4 g) and p-benzoquinone (41 g) in ethanol (230 ml) were refluxed for 20 h.

The mixture was refrigerated overnight and then filtered to give

2,3,6,7-tetramethyl-1,4,4aa,5,8,8aP,9aa,lOa~-octahydroanthracene-9,10-dione (4) (52 $4,m.P. 229-230" (ethanol) (lit.19 206-208") (Found: C, 7 9 . 5 ; H, 9 . 0 . Calc. for C18H2402: C, 7 9 . 4 ; H 8.9%). 1.r. (KBr disc): 2985, 2910, 2865, 1695, 1445, 1425, 1230, 1175, 920, 785, 470 cm-'. m/z: 273 (18%),272 (M, 90), 239 (23), 221 (45), 211 (16), 203 (13), 202 (65L 201 ( 2 4 , 190 (23), 189 (35), 188 (29), 187 (26), 185 (13), 175 (351, 173 (14), 172 (22), 161 (11), 159 (11), 157 ( l l ) , 147 (18), 109 (181, 108 (14), 107 (51), 105 (30), 95 (11), 94 ( l o ) , 93 (GO), 92 (14), 91 (loo), 79 (261, 77 (51), 67 (19), 65 (20), 55 (16), 53 ( 1 3 , 43 ( l l ) , 41 ( 2 9 , 39 (19). Base-Catalysed Epimerization of Diketone (4) The diketone (4) (52 g) and ethanolic potassium hydroxide (7.5%, 10 ml) in ethanol (800 ml) were stirred at 50" for 1 h. The mixture was cooled and then filtered to give 2,3,6,7-tetramethy1-1,4,4aa,5,8,8a~,9a~,10aa-octahydroanthracene-9,10-dion (5) (52 g), m.p. 302-304" (acetic acid) (lit.2 307") (Found: C, 7 9 . 2 ; H, 9 . 0 . Calc. for Cl8H2402: C, 7 9 . 4 ; H, 8.9%). N.m.r. data: see Tables 1-3. 1.r. (KBr disc): 2980, 2890, 1690, 1430, 1380, 1295, 1215, 1170, 1 1 1 O ~ m - ~m/z: . 272 (M, 7%), 221 (42), 121 (25), 120 (13), 119 (24), 109 ( l l ) , 107 (43), 105 (27), 94 ( l o ) , 93 (74), 92 (161, 91 ( l o o ) , 79 (33), 77 (56), 67 (17), 65 (231, 55 (16), 53 (lS), 43 (12), 41 (35), 39 (20). Borohydride Reduction of Ketone (5) The diketone (5) (52 g) and sodium borohydride (35 g) were stirred in tetrahydrofuran ( 2 . 5 1) and ethanol (100 ml) at room temperature overnight. The mixture was poured onto cold aqueous HCI (1 N) and then filtered. The precipitate was washed well with water and dried to give a mixture (30 g) of diol (10) 57% and diol (11) 43% (by gas chromatography). A mixture of diols (10) and (11) (180 mg) and a few crystals of 4-(dimethy1amino)pyridine was stirred in acetic anhydride (8 ml) at room temperature for 22 h. The mixture was poured onto iced water and then filtered. The precipitate was washed well with water and dried (98% yield of acetate mixture). Chromatography on silica (dichloromethane) gave, in order of elution: (i) 9,10-Diacetoxy-2,3,6,7-tetramethyl-1 , 4 , 4 a a , 5 , 8 , 8 a P P 9 ~ , 91aOa, ~ , 1 Oaa-decahydroanthracene (13), m.p. 255-256" (benzene) (Found: C, 7 3 . 2 ; H, 8 . 9 . C22H3204 requires C, 7 3 . 3 ; H, 8.9%). N.m.r. data: see Tables 1-3. 1.r. (CHC13): 2900, 2820, 1720, 1425, 1370, 1220, 1110, 1040, 1015, 955 cm-l. m/z: 360 (M,6%), 241 (16), 240 (76), 225 (27), 197 ( l l ) , 171 (281, 170 (loo), 169 (29), 158 (45), 157 (34), 156 (18), 155 (24), 144 (12), 143 (741, 142 ( l l ) , 133 (13), 132 (13), 129 ( l l ) , 128 ( l o ) , 121 (42), 120 (35), 119 (601, 107 (28), 105 (37), 95 (111, 93 (18), 91 (37), 79 (14), 77 (12), 67 (111, 43 (80), 41 (16). 8aPP9P,9aPP 1OP, 1Oaa-decahydroanthra(ii) 9,1O-Diacetoxy-2,3,6,7-tetramethyl-1,4,4aa,5,8, cene (12), m.p. 223-223.5" (benzene) (Found: C, 7 3 . 6 ; H, 8 . 9 . C22H3204 requires C, 7 3 . 3 ; H, 8.9%). N.m.r. data: see Tables 1-3. 1.r. (CHC13): 2890, 2820, 1720, 1430, 1370, 1220, l9

Hinshaw, J. C., Org. Prep. Proced. Int., 1972, 4, 211.


1045, 1020, 945 cm-I. m/z: 360 (M, 2%), 241 ( l l ) ,240 (551, 225 (24), 171 (31), 170 (loo), 169 (31), 158 (37), 157 (32), 156 (15), 155 (24), 143 (58), 142 (lo), 133 (131, 132 (ZO), 131 (lo), 121 (38), 120 (32), 119 (59), 107 (24), 105 (32), 95 (lo), 93 (15), 91 (34), 79 (12), 4 3 (63), 41 (13). The diacetate (13) was refluxed with potassium carbonate in methanol for 5 h. The mixture was cooled and then filtered. The precipitate was washed well with methanol to give the methanol-insoluble 2,3,6,7-tetramethyl-1,4,4aa,5,8,8a~,9~,9a~,10a,10a0:decahydroanthracene-9,lO-diol( l l ) , m.p. >330° (sublimation) (Found: Mt*, 276.2087. C18H2802 requires M+', 276.2089). N.m.r. data: see Tables 1-3. 1.r. (KBr disc): 3250, 2980, 2870, 2820, 1430, 1340, 1260, 1180, 1055, 980, 800 cm-l. m/z: 277 (22%),276 (M,98), 170 (23), 137 (45), 135 (261, 133 (20), 123 (231, 122 (231, 121 (go), 120 (44h 119 (67), 109 (56), 108 (36), 107 (loo), 105 (56), 95 (50), 93 (68), 91 (87), 81 (25), 79 (42), 77 ( 3 3 , 69 (24), 67 (40), 57 (20), 55 (361, 43 (34), 41 (54). The diacetate (12) was similarly treated to give 2,3,6,7-tetramethyl-l,4,4aa,5,8,8aB,9~,9aB,1OB,1Oaoc-decahydroanthracene-9,lO-diol (lo), m.p. >330° (sublimation) (Found: C, 78.0; H, 10 3. C18H2802 requires C, 78.2; H, 10.2%). N.m.r. data: see Tables 1-3. 1.r. (KBr disc): 3275, 2980, 2885, 1430, 1055, 980 cm-l. m/z: 276 (M, 28%), 259 (Zl), 258 (32), 171 (26), 170 (71), 169 (26), 158 (20), 157 (251, 143 (28), 134 (20), 133 (23), 122 (36), 121 (96), 120 (71), 119 (72), 109 (311, 108 (34), 107 (loo), 105 (59), 95 (31), 93 (54), 91 (771, 79 (281, 77 (29), 67 (29), 55 (261, 43 (291, 41 (39).

Reaction of the Diol Mixture (10) and (11) with p-Toluenesulfonyl Chloride A mixture ( 1 . 8 g) of diols (10) and (1 1) (57 : 43) was stirred with p-toluenesulfonyl chloride ( 1 . 9 g) in pyridine (120 ml) at 40" for 4 days. The mixture was poured onto iced water, filtered and the precipitate washed with water. The crude product was taken up in boiling chloroform, filtered to remove insoluble unchanged diols, and the filtrate evaporated to dryness. Chromatography on silica (dichloromethane/hexane 3 : 1) gave in order of elution: (i) 9,l0-Dichloro-2,3,6,7-tetramethyl-1,4,4a,5,8,8a,9a,9a,lO,l Oaa-decahydroanthracene (20) (80 mg), m.p. 262-264' (chloroform) (Found: C, 6 9 . 1 ; H, 8 . 5 . Ci8H26C12 requires C, 6 9 . 0 ; H, 8.4%). N.m.r. data: see Tables 1-3. 1.r. (KBr disc): 2980, 2890, 2840, 1440, 1370,

1320, 1285, 1220, 1130, 1010, 645, 450 cm-l. m/z: 316 (7%), 314 (42), 312 (M, 61), 278 (28), 276 (37), 241 (401, 240 (951, 225 (23), 171 (44), 170 (54), 169 (31), 158 (25), 156 (241, 155 (33), 143 (38), 141 (21), 132 (27), 129 (21), 121 (55), 120 (80), 119 (loo), 107 (44), 105 (50), 91 (53), 79 (23), 77 (281, 41 (24). (ii) 1O-Chloro-2,3,6,7-tetramethyl-l,4,4aa,5,8,8a~,9a,9a~,10~,1Oaa-decahydroanthracen-901 (21) (430 mg), m.p. 218-219" (chloroform) (Found: C, 73.3; H, 9 . 4 . C18H27C10 requires C, 73.3; H, 9.2%). N.m.r. data: see Tables 1-3. 1.r. (KBr disc): 3450, 3350, 2980, 2910, 2840, 1435, 1375, 1220, 1145, 1070, 1055, 1030, 925, 795, 620cm-l. m/z: 296 (5%), 294 (M, 14), 276 (51), 170 (32), 157 (28), 143 (31), 121, (51), 120 (68), 119 (87), 107 (54), 105 (65), 93 (41), 91 (loo), 79 (431, 77 (42), 67 (401, 65 (23), 55 ( 3 9 , 53 (251, 43 (38L 41 (78), 39 (31). 1ON,(iii) 2,3,6,7-~etramethyl-9,10-bis(4-methylphenylsu/fonyloxy)-1,4,4aa,5,8,8a,9,9a, 10aa-decahydroanthracene (18) (470 mg), m.p. 212-213" (dec.) (chloroform) (Found: C, 6 5 . 5 ; H, 6 . 9 ; 5, 1 0 . 6 . C32H4006S2 requires C, 6 5 . 7 ; H, 6 . 9 ; S, 11.0%). N.m.r. data: see Tables 1-3. 1.r. (KBr disc): 2980, 2900, 2820, 1600, 1440, 1360, 1340, 1190, 1170, 910, 840, 810, 680, 670, 580, 550 cm-l. m/z: 584 (M, 3%), 95 (12), 83 (16), 79 ( l o ) , 77 ( l l ) , 73 (211, 70 ( l l ) , 69 (31), 60 (20), 57 (301, 56 (161, 55 (46), 45 (631, 44 (411, 43 (loo), 42 (19), 41 (61), 39 (23), 31 (22). (iv) 2,3,6,7-Tetramethyl-10-(4-methylphenylsulf0ny10xy-1,4,4aa 5 , 8 , 8 a 9 , 9 a l O lOaadecahydroanthracen-9-01(17) (390 mg), m.p. 155-158" (dec.) (chloroform) (Found: C, 6 9 . 5 ; H, 7 . 9 ; S, 7.4. C25H34O4S requires C, 6 9 . 7 ; H, 8 . 0 ; S, 7.4%). N.m.r. data: see Tables 1-3. 1.r. (KBr disc): 3560, 2970, 2885, 2830, 1600, 1435, 1340, 1170, 890, 670, 575, 550 cm-'. m/z (20 eV): 430 (M, 0.3%), 258 (17), 241 (20), 240 (loo), 225 (12), 171 (19), 170 (48), 169 (21), 157 (14), 155 ( l 5 ) , 143 ( l l ) , 132 (19), 121 (IS), 120 ( 1 9 , 119 (13), 107 (11). m/z (70 eV): (430 M, not detected), 149 (26%), 97 (13), 95 (121, 91 (271, 85 (371, 84 ( l l ) , 83 (32h 8 1 (27), 77 (12), 71 (211, 70 (14), 69 (74), 68 (151, 67 (201, 60 (321, 57 (75), 56 55 (631, 53 (12), 27 (12), 45 (421, 44 (23), 42 (21), 40 (loo), 39 (26). (v) 2,3,6,7-~etramethyl-l0-(4-methylphenylsulfonyloxy~-1,4,4aa,5,8,8a~,9~,9a~,l Oa.1 0aa decahydroanthracen-9-01(16) (450 mg), m.p. 175-177" (dec.) (chloroform/hexane) (Found: C,


6 9 . 6 ; H, 8 . 0 ; S, 7.3. C25H3404S requires C, 6 9 . 7 ; H, 8 . 0 ; S, 7.4%). N.m.r. data: see Tables 1-3. 1.r. (KBr disc): 3250, 2900, 2820, 1600, 1440, 1360, 1180, 920, 810, 670, 590 cm-'. m/z: 430 (M, not detected), 149 (16%),97 (12), 95 (14), 93 (12), 91 (131, 85 (231, 83 (1% 82 ( l o ) , 81 (31), 79 (12), 77 ( l o ) , 73 (22), 71 (16), 70 (12), 69 (56), 67 (221, 60 (32), 57 (42), 56 (16), 55 (65), 53 (15), 45 (60), 44 (41), 43 (loo), 42 (25), 41 (go), 39 (30), 32 (14), 31 (13). Treatment of the Tosylates (17) a n d (18)with Chloride The hydroxy tosylate (17) was stirred overnight in warm pyridine (40") with an excess of lithium chloride and ammonium chloride. The resulting solution gave a single peak on gas chromatography which corresponded to the chloride (21) by mixed gas chromatographic injections. On similar treatment of the ditosylate (18), no chloro derivatives could be detected in the product. Lithium Aluminium Hydride Reduction of the Product Mixture from Tosylation of Diols (10) a n d (11) The mixture (16), (17), (18), (20) and (21) (20 g) was placed in a thimble over a refluxing solution of tetrahydrofuran (800 ml) and lithium aluminum hydride (12 g), and extracted into the solution during 12 h. Reflux was continued for a further 4 h; the mixture was then cooled and poured onto iced water (1 1.). The resulting suspension was filtered and the precipitate washed well wlth chloroform. The aqueous filtrate was shaken with chloroform, the combined chloroform extracts washed with aqueous sodium chloride solution and dried, before evaporation to dryness. The product ( 1 0 . 3 g) contained hydrocarbon (25) (21%), alcohol (24) (25%), alcohol (23) (33%) and unidentified material (21%, by gas chromatography). Chromatography on silica (chloroform/hexane 4 : 1) gave 2,3,6,7-tetramethyl-l,4,4aa,5,8,8aB,9,9aB,lO,l Oaot-decahydroanthracene (25) ( 3 . 2 g), m.p. 238-239.5" (chloroform) (Found: C, 8 8 . 7 ; H, 1 1 . 8 . ClgH2g requires C, 8 8 . 5 ; H, 11.6%). N.m.r. data: see Tables 1-3. 1.r. (KBr disc): 2980, 2890, 2810, 1440, 1375, 1295, 1225, 1145 cm-l, m/z: 244 (M, 60%), 229 (24), 202 (25), 174 (21), 173 (23), 159 (25), 147 (21), 133 (23), 122 (22), 121 (52), 120 (83), 119 (82), 107 (56), 106 (231, 105 (72), 95 (26), 92 (25), 91 (821, 79 (46), 77 (33), 69 (231, 67 (33), 55 (32), 53 (221, 43 (22), 41 ( l o o ) , 39 (29). Further elution gave, after an intermediate fraction, 2,3,6,7-tetramethyl-1,4,4aot,5,8,8aBB90(,9a~,1O,lOaa-decahydroanthracen-9-ol (241, m.p. 254-255" (chloroform) (Found: C, 8 3 . 3 ; H, 11.0. C18H280 requires C, 8 3 . 0 ; H, 10.8%). N.m.r. data: see Tables 1-3. 1.r. (KBr disc): 3500, 3385, 2980, 2885, 1430, 1370, 1215, 1145, 1055, 890cm-l. m/z: 260 (M, 12%), 242 (44), 160 (26), 157 (29), 145 (341, 131 (25), 123 (64), 122 (31), 121 (SO), 120 (loo), 119 (71), 109 (28), 107 (62), 105 (81), 95 (27), 93 (41), 91 (74), 81 (32), 79 (38), 77 (30), 67 (36), 55 (36), 43 (33), 41 (84), 39 (26), 29 (471, 27 (26). Continued elution gave 2,3,6,7-tetramethyl-1,4,4aa,5,8,8a~,9~,9a~,lO,lOaot-decahydroanthracen-9-01 (23), m.p. 244-245" (chloroform) (Found: C, 8 2 . 6 ; H, 10.9. ClgH2gO requires C, 8 3 . 0 ; H, 10.8%). N.m.r. data: see Tables 1-3. 1.r. (KBr disc): 3250, 2970, 2890, 2820, 1430, 1380, 1185, 1065, 990 cm-'. m/z: 260 (M, 55%), 242 (12L 123 (30), 122 (24), 121 (45), 120 (39), 109 (27), 107 (75), 105 (42), 95 (30), 91 (70), 81 (24), 79 (42), 77 (33), 67 (39), 55 (42), 53 (24), 43 (42), 41 (loo), 39 (301, 29 (60), 28 (57). The total weight of alcohols (23) and (24) recovered was 4 . 0 g.

A mixture of the alcohols (23) and (24) (4 g), pyridinium chlorochromate (5 g) and dichloromethane (400 ml) were stirred at room temperature for 4 h. Ether was added and the mixture filtered through Celite. The filtrate was evaporated to give the ketone ( I ) , m.p. 268-269" (sealed tube) (chloroform) (Found: C, 8 3 . 4 ; H, 1 0 . 3 . Cl8Hz6O requires C, 8 3 . 7 ; H, 10.1%). N.m.r. data: see Tables 1-3. 1.r. (KBr disc): 2980, 2895, 1705, 1440, 1380, 1300, 1120, 1075, 1010 cm-'. m/z: 259 (13%), 258 (M,49), 243 ( l l ) , 240 ( l l ) , 135 (14), 133 ( l l ) , 121 (34), 120 (25), 119 (36), 108 (15), 107 (52), 105 (46), 95 ( 1 4 , 94 ( l l ) , 93 (56), 92 (13), 91 (loo), 81 ( l o ) , 79 (47), 77 (511, 69 (111, 67 (29), 65 (21), 55 (26), 53 ( 2 4 , 43 (18), 41 (66), 39 (25).


Reduction of Diketone (4) to the Diols (34) and (36) The diketone (4) (250 mg) and sodium borohydride (100 mg) were stirred in aqueous tetrahydrofuran (40 ml, 10%v/v) at room temperature for 2 h. The mixture was then poured onto dilute HCI (1 N) and filtered. The precipitate was washed with water and the filtrate was extracted with chloroform. The chloroform extracts were dried (sodium sulfate) and evaporated to dryness. Gas chromatographic analysis of the combined precipitate and extract (235 mg) showed two components in the ratio 75 : 25. On treatment with boiling chloroform, the major component dissolved, and the insoluble minor component was collected by filtration and recrystallized to give 2,3,6,7-tetramethyl-I,4,4aa5,8,8a~,9~,9aa,1Oa,10afidecahydroanthracene-9,lO-diol(36), m.p. >33O0 (methanol) (Found: M*', 276.2097. C18H2802 requires M+*, 276.2089). 1.r. (KBr disc): 3360. 2980, 2900, 1460, 1195, 1090, 1070, 1035, 1015, 910, 660, 590 cm-'. m/z: 276 (M, 7%), 170 (27), 121 (35), 120 (30), 119 (37), 108 (24), 107 (57), 105 (42), 95 (33), 94 (20), 93 (62), 91 (loo), 79 (51), 77 (46)' 67 (60), 65 (23), 55 (38), 53 (20), 43 (40), 41 (691, 39 (24). The chloroform-soluble major component was 2,3,6,7-tetramethyl-1,4,4aa,5,8,8aP,9fiP9aa,10/3,1Oap-decahydroanthracene-9,lO-diol (34), m.p. 229-233" (benzene) (Found: C, 77.9; H, 1 0 . 4 . C18H2802 requires C, 78.2; H, 10.2%). ' H n.m.r. (293 K): 6 1 . 5 9 , 1 . 6 5 , br s , methyls; 3.67, br d , Wh/2 12 HZ, H9,lO. 'H n.m.r. (223 K): 6 1 . 5 2 , 1 . 58, 1. 59, 1 . 6 4 , all br S, methyls; 3 . 6 1 , br s, Wh/2 6 HZ, H 10; 3.71, dd, J 1 1 . 5 , 3 . 5 Hz, H9. 13cn.m.r.: see Table 4. 1.r. (CHCI3): 3530, 2880, 1440, 1380, 1330, 1145, 1130, 1110, 1090, 1005, 995, 960 cm-'. m/z: 276 (M, lo%), 170 (35), 143 (21), 121 (23), 119 (31), 108 (20), 107 (511, 105 (45), 95 (28), 93 (57), 91 (loo), 79 (44), 77 (46), 67 (60), 65 (24), 55 (46), 53 (231, 44 (28), 43 (47), 41 (71), 39 (24).

Acetylation of the Diol (36) The diol (36) (150 mg), pyridine (5 ml) and acetic anhydride (5 ml) were stirred with a few crystals of 4-(dimethy1amino)pyridine at room temperature for 3 h. Iced water (40 ml) was added and the mixture filtered. The precipitate was washed with water to give 9,lO-diacetoxy2,3,6,7-tetramethyl-1,4,4aa5,8,8a~,9fiB9aal Oa,lOap-decahydroanthracene (35) (80 mg), m.p. 204-207" (benzene) (Found: C, 7 3 . 3 ; H, 9 . 1 . C22H3204 requires C, 73.3; H, 9.0%). 'H n.m.r. (293 K): 6 1 . 56, 1 . 6 0 , br s, methyls; 2 . 0 6 , br s, acetate methyls; 2 . 3 4 , br m, H9a,10a; 2 . 5 1 , br m, H4a,8a; 4 . 8 7 , dd, J 1 1 . 6 , 4 . 5 H z , H9,lO. 'H n.m.r. (223K): 6 1 . 5 0 , 1 . 5 3 , br s, methyls; 2.06, s, acetate methyls; 2.31, m, H 9a,10a; 2.47, m, H4a,8a; 4.75, dd, J 1 2 . 0 , 4 . 9 H z , H9,lO. 13c n.m.r.: see Table 4. 1.r. (KBr disc): 2980, 2900, 1725, 1435, 1370, 1220, 1020, 985, 600 cm-I. m/z: 360 (M, 3%), 240 (25), 171 (19), 170 (68), 169 (14), 158 (33), 157 (25), 155 (12), 146 (30), 143 (44), 132 ( l o ) , 131 ( l l ) , 121 (18), 120 ( l l ) , 119 (33), 107 (26), 105 ( 2 3 , 95 (IS), 94 (21), 93 (18), 91 (36), 79 (15), 77 (12), 67 (17), 55 ( l o ) , 43 (loo), 41 (16).

Acknowledgment We thank Lynette Lambert for assistance in obtaining n.m.r. spectral data.

Manuscript received 22 April 1988