synthesis and diels–alder reactions of ( e ...

Synthesis and Diels-Alder reactions of (E)-6,6-dimethoxy-3-hexen-2-one

PETER YATES A N D STEPHEN PAUL DOUGLAS Lasl~ Miller Chernical Laboratories, Urzicersity of Tororzto, Toronto, Ont., Conada M5S IAI

Received February 2, 1982

PETER YATES and STEPHEN PAUL DOUGLAS. Can. J. Chem. 60,2760 (1982). Treatment of 3,3-dimethoxypropanal (2) with (acetylmethylene)triphenylphosphorane (4) gives (E)-6,6-dimethoxy-3-hexen-

2-one (5). Reaction of 5 with cyclopentadiene, 1,3-cyclohexadiene, anthracene, and 1,3-diphenylisobenzofuran gives Diels-Alder adducts, which on hydrolysis are converted to the corresponding keto aldehydes. Attempts to effect intramolecular aldol condensation of the latter were unsuccessful. Hydrolysis of the exo-acetyl adduct from 1,3-diphenylisobenzofuran with aqueous formic acid gives 4-acetyl-2,3,3a,4,5,9b-hexahydro-5,9b-diphenylnaphtho[1,2-b]furan-2,5-diol, via aldehyde formation and hydro- lytic cleavage of the ether bridge. The adducts from cyclopentadiene under anhydrous acid conditions give 3-acetyl-9-methoxy- tetracycl0[4.3.0.0'~~.0~~~]nonane (27).

PETER YATES et STEPHEN PAUL DOUGLAS. Can. J. Chem. 60,2760 (1982). Le dimtthoxy-3,3 propanal (2) rCagit avec I'(acCtylmCthylene) triphenylphosphorane (4) en donnant la (E)-dimethoxy-6,6

hexene-3 one-2 (5). Le compose 5 reagit avec le cyclopentaditne, le cyclohexadiene-1,3, I'anthractne et le diphCnyl-1,3 isobenzofuranne en donnant des adduits de Diels Alder qui, parhydrolyse, donnent les ceto aldehydes correspondants. On a essay6 vainement de realiser une condensation aldolique intramoleculaire avec ces cttoaldthydes. L'hydrolyse d e I'adduit exo-acktyl provenant du diphknyl-1,3 isobenzofuranne, avec l'acide formique aqueux, donne I'acCtyl-4 hexahydro-2,3,3a,4,5,9b diphenyl-5,9b naptho[l,2-b]furannediol-2,5 par l'intermkdiaire de la formation de I'aldehyde et du clivage, par hydrolyse, du pont ether. Les adduits provenant du cyclopentaditne dans un milieu acide anhydre donnent I'acCtyl-3 methoxy-9 t~tracycl0[4.3.0.O~~~.O~~~]nonane (27).

[Traduit par le journal]

Shakespeare said of Cleopatra "Age cannot wither her, nor custom stale Her infinite variety." The same could be said of the Diels-Alder reaction. In recent years the scope of this reaction has been greatly expanded by the utilization of a large variety of dienes and dienophiles. We report here on the synthesis and Diels-Alder reactions of the dienophile 6,6-dimethoxy-3-hexen-2-one. We have shown that this can serve, via hydrolysis of its Diels-Alder adducts, as an equivalent of the dienophile 3-hexene-2,6-dione, but we have not been successful in effecting the intramolecular aldol condensation of the keto aldehydes resulting from such hydrolyses, which would have permitted its use as an equivalent of the dienophile 2,5-cyclohexadienone.

Base-catalyzed addition of two equivalents of methanol to propiolaldehyde (1) (1) gave P,P- dimethoxypropionaldehyde (2) (2), containing 10% of P-methoxyacrolein (3) as shown by 'H nmr spectroscopy. This mixture was treated with (acetylmethy1ene)triphenylphosphorane (4) to give 6,6-dimethoxy-3-hexen-2-one (5) (Scheme 1). No effort was devoted to removal of 3 from the original mixture since it was anticipated that it would be unreactive in a Wittig reaction with 4 because of electron donation to the aldehyde group by the methoxyl group. This was indeed found to be the case in that only the enone 5 was formed in the reaction of the mixture of compounds 2 and 3 with

the Wittig reagent 4 and that 3 (2) alone failed t o react with 4.

Their spectrum of 5 showed a strong band at 5.95 pm and a medium band at 6.12 p m in accord with the presence of an a ,P-unsaturated ketonic system; a strong band a t 10.25 pm suggested that the product has the trans (E) configuration as in 5 (3). In its 'H nmr spectrum the olefinic proton signals appear as a doublet at 6 6.02 ( J = 15 Hz) and a doublet of triplets at 6 6.63 ppm ( J = 15 and 7.5 Hz); the magnitude of the larger coupling constant established that the product has the trans (E) configuration. The uv spectrum of 5 (A,,, (pentane) 216 nm (E 9500), 321 nm ( E 35)) is in accord with the presence of a monosubstituted a$-unsaturated ketonic function. In its I3C nmr spectrum the a and p ethylenic carbon signals occur at 6 133.6 and 142.3 ppm, respectively (cf. the corresponding signals in 3-buten-2-one at 6 138.5 and 129.3 ppm).

Reaction of 5 with a large excess of cyclopentadiene at 100-110°C in the absence of solvent for three days gave a 55:45 mixture of the stereo- isomeric Diels-Alder adducts 6 and 7 (Scheme 2) in almost quantitative yield. Individual assignments of structure to the endo and exo isomers' were made from their IH nmr spectra on the basis of decoupling experiments and the following earlier

'The designations endo and exo are made with reference t o the acetyl group.

0008-4042/82/222760-06$0 1 .00/0 01982 National Research Council of Canada/Conseil national de recherches du Canada

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YATES AND DOUGLAS

HC=CCHO MeOH * (Me0)2CHCH2CH0 + MeOCH=CHCHO

2 3

observations regarding the spectra of bicyclo- [2.2. llheptenes: (i) signals of exo protons and the protons of exo substituents appear downfield relative to those of the corresponding endo protons (4) and (ii) electron-withdrawing endo substituents deshield the bridgehead (5) and often shield the olefinic protons nearest to them (6). Thus under the reaction conditions used there is a slight preference for formation of the endo adduct. It is probable that under these conditions the reaction is under kinetic control (7) and the modest stereoselectivity is analogous to that observed in the cases of other

i simple a,P-unsaturated carbonyl compounds under such circumstances (7, 8). Hydrolysis of 6

I

with 1.2 N hydrochloric acid in tetrahydrofuran 1 gave the keto aldehyde 8 (Scheme 2) whose ir ' spectrum showed strong bands at 5.81 and 5.85 pm.

Reaction of 5 with 1,3-cyclohexadiene at 100- 120°C yielded the adducts 9 and 10 (Scheme 2). The individual stereochemical assignments are again based on their 'H nmr spectra, since bicyclo[2.2.2]- octenes have been observed to exhibit the same

downfield shift of the signals of exo relative to endo protons as in the case of bicyclo[2.2. llheptenes (4, 6). Again the endo isomer was formed in slight preponderance. Hydrolysis of this isomer gave the keto aldehyde 11, whose ir spectrum showed strong bands at 5.80 and 5.85 pm.

Cycloaddition of 5 to anthracene was best effected with an excess of the dienophile at 150°C (reaction did not occur at 120°C). Adduct 12 (Scheme 3) was thus obtained in 77% yield (based on anthracene). This product was hydrolyzed to the keto aldehyde 13.

The Diels-Alder reaction of 5 with 1,3-diphenylisobenzofuran was carried out in boiling benzene. After 3 days, reaction was complete to give a mixture of the exo (14) and endo (15) adducts in a 4:l ratio (Scheme 4). Individual assignments of stereochemistry were made on the basis of a comparison of the 'H nmr spectra of the adducts, since it has previously been shown that in systems of this type endo protons again are shielded relative to exo protons (9, 10). The carbonyl-stretching

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2762 CAN. J . CHEM. VOL. 60, 1982

bands in the ir spectra of 14 and 15 occur at unusually long wavelength (5.92 pm); this may be the result of interaction of the carbonyl group with a methoxyl group or the phenyl substituent at the adjacent bridgehead position. Hydrolysis of 14 with 1.2 N hydrochloric acid in tetrahydrofuran gave the expected keto aldehyde 16, but the reaction was capricious; in some runs the product underwent further reaction and in others hydrolysis was incomplete. Treatment with aqueous 90% formic acid (1 1) led to hydrolysis of both the acetal and ether bridge functions, giving hemiacetal 17 in high yield. In the 'H spectrum of 17 the large coupling constant (J = 12 Hz) between H-4 and H-3a is attributable to a trans diaxial relationship between these protons, and the further coupling of H-3a with only one of the H-3 protons can be

interpreted in terms of the preferred conformation of the hemiacetal ring. As in the case of 15 the carbonyl-stretching band in the ir spectrum of 17 occurs at an unusually long wavelength (5.95 pm): here the major contributing factor is probably hydrogen-bonding of the carbonyl group with the adjacent hydroxyl group. Such hydrogen bonding is also evidenced by the relatively low field position (6 4.63) of the signal of the tertiary hydroxyl proton in the 'H nmr spectrum of 17.

It was hoped that the keto aldehydes of type 8 could be induced to undergo intramolecular aldol condensation to give cyclohexenones of type 18, products that are formally derived from Diels- Alder reactions of 2,5-cyclohexadienone. An analogous condensation was observed by Johns (12) on treatment of the keto aldehyde 19 with alcoholic potassium hydroxide. It was recognized that compounds of type 8 differ from 19 in having a trans rather than a cis relationship between the acetyl and acetaldehyde groups, and although Valenta and co-workers (13) have observed the aldol condensation in basic medium of the trans isomer 20 to give a cycloheptenone, there appears to have been no report of the closure of a six-membered ring in the trans series. It was considered that under the basic (or acidic) conditions of the aldol reaction equilibration of the trans compounds of type 8 would occur with their cis isomers via epimerization at the carbon atom bearing the acetyl group and that these isomers would then undergo the aldol reaction. However, no simple aldol condensation products could be detected when compounds of type 8 were subjected to a variety of basic conditions analogous to those used in the cases of 19 and 20 (12, - 13) and related cases (14); only starting

AN 190% HCO2H aqueous HCI

16 17

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YATES AND DOUGLAS 2763

conditions to give a product of type 26. However, dCH0 treatment of the mixture with p-toluenesulfonic

/ acid in benzene gave compound 27 and a product

\ I H k that is tentatively assigned structure 28, together with polymeric products (Scheme 5). The 'H nmr

o spectra of 27 and 28 showed that each retained a 18 19 single methoxyl group. The ir spectrum of 27

showed a carbonyl-stretching band at 5.90 pm, indicating conjugation of the acetyl group with an ethylenic double bond or cyclopropyl group. That the latter is the case was established by the I3C nmr spectrum of 27, which showed no olefinic carbon

M e 0 signals. Compounds 27 and 28 are considered to 20

material or polymeric products were isolated in each case. Attempts at acid-catalyzed cyclization (15) were also of no avail.

In case these results were due to the failure of the keto aldehydes of type 8 to undergo equilibration with their cis isomers, a preliminary investigation was made of the direct synthesis of such an isomer. Ultraviolet irradiation of 5 in benzene gave a - 1: 1 mixture of 5 and its cis isomer, 21, as shown by its 'H nmr spectrum. Reaction of this mixture with cyclopentadiene followed by hydrolysis gave a mixture whose 'H nmr spectrum indicated that it consisted of the cis isomers 22 and 23 together with

8 and the other trans keto aldehyde. However, treatment of this mixture under several of the aldol conditions referred to above resulted only in the epimerization of the cis to the trans keto aldehydes.

In case the failure of the cyclization reactions was associated with the presence of the ethylenic double bond in compounds of type 8, compounds 6 and 9 were hydrogenated and hydrolyzed to give 24 and 25, respectively. But again aldol condensation could not be effected.

An attempt was also made to effect cyclization of a mixture of the keto acetals 6 and 7 under acidic

arise from the exo keto acetal7 by the routes shown in Scheme 5.

Experimental Melting points were determined with a Thomas-Hoover

capillary melting point apparatus, and are uncorrected. Infrared spectra were taken in CHCI, solution; band intensities are strong, unless designated as medium (m) or weak (w). Proton and carbon-13 nuclear magnetic resonance ( IH and I3C nmr) spectra were taken in CDCI, solution. Unless otherwise stated, solutions in organic solvents were dried over anhydrous MgSO, and concentrated by means of a Buchi "Rotovapor (R)" rotary evaporator.

(E)-6,&Dimerhoxy-3-l1exen-2-one (5) Propargyl alcohol was oxidized to propiolaldehyde (1) with

chromic acid (1) in 45% yield; bp 58-60°C (lit. ( I ) bp 59-61°C); ir h,,,: 3.53 (w),4.78(w),5.96 pm; 'Hnmr6: 9.17(s, lH),3.58(s, 1H). Base-catalyzed addition of two molar equivalents of methanol to the aldehyde (2) gave P,P-dimethoxypropionaldehyde (2) in 80% yield; ir A,,,: 3.59 (w), 5.82 p m ; 'H nmr6: 2.70 (m, 2H), 3.40 (s, 6H), 4.83 (t, J = 5 Hz, IH), 9.73 (t, J = 2 Hz, 1H). The crude product, which contained 10% of P-methoxyacrolein (3) (2) as shown by IH nmr spectroscopy, was used without further purification.

A solution of aldehyde 2 (23.76g, 201 mmol) and (acetylmethylene)triphenylphosphorane (4) (16) (64.lg, 201 mmol) in anhydrous tetrahydrofuran (250 mL) was boiled under reflux for 5 days under a constant positive pressure of nitrogen. The solution was concentrated and the precipitated triphenylphosphine oxide was separated by suction filtration and washed with cold benzene. The combined filtrate and washings were concentrated, the concentrate was cooled to -7bC, and a second crop of triphenylphosphine oxide was removed. Concentration of the filtrate followed by flash distillation (lOO"C, 0.05 Torr) of the residue gave 5 as a colorless liquid (26.44g, 83%), bp 51-53°C (0.05 Torr); ir h,,,: 5.93, 6.12 (m), 7.35 (w) pm; uv A,,, (E) (pentane): 216 (9500), 321 (35) nm; 'H nmr 6: 2.22 (s, 3H), 2.53 (m, 2H), 3.37(s, 6H),4.43 (t, J = 6Hz, lH), 6.02 (d, J = 15Hz, lH), 6.68 (dt, J = 7.5 Hz, 15 Hz, 1H); I3C nrnr 6: 26.8 (q), 36.2 (t), 53.2 (q), 103.1 (d), 133.6 (d), 142.3 (d), 198.05 (s). Anal. calcd. for C,H,,O,: C 60.74, H 8.92; found: C 60.49, H8.87.

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2764 CAN. J. CHEM. VOL. 60. 1982

Diels-Alder reaction of 5 with cyclopenradiene. Fortnation of endo-5-acetyl-exo-6(2,2-ditnethoxyethyl)bicyclo[2.2.1]- hept-2-ene (6) and exo-5-acetyl-endo-6(2,2-dirnethoxyethyl)bicyclo[2.2. Ilhept-2-ene (7)

Compound 5 (l.OOg, 6.32 mmol) and 1,3-cyclopentadiene (6.6g, 100 mmol) were placed in a Carius tube (15 x 20 x 250 mm) and the tube was cooled (- 196"C), sealed, and heated for 3 days at 110-120°C. The tube was cooled and opened and the contents were subjected to high vacuum pumping (0.01 Torr) at room temperature to remove most of the dimerized diene. Chromatography (silica gel, 7:3 hexane and ethyl acetate) afforded adducts 6 and 7 (total 1.37g, 97%); the endo-acetyl isomer 6 had the longer retention time and comprised 57% of the mixture. Compound 7: ir A,,,: 5.86 pm; 'H nmr6: 1.50(m, 2H), 1.85(m, 2H), 2.05 (m, lH), 2.10(s, 3H), 2.60(m, 2H), 3.16(m, IH), 3.27 (s, 3H), 3.30 (s, 3H), 4.35 (t, J = 5 Hz, IH), 5.83 (m, IH), 6.20(m, 1H). Compound 6: ir k,,,: 5.86 pm; ' H nmr 6: 1.42 (m, 2H), 1.55 (m, 2H), 2.02 (m, lH), 2.23 (s, 3H), 2.50 (m, lH), 2.88 (m, 2H), 3.30 (s, 6H), 4.3 1 (t, J = 5 Hz, lH), 6.18 (m, 2H); 13C nmr 6: 28.4 (q), 36.6 (d), 38.2 (t), 45.9 (d), 46.4 (t), 47.2 (d), 52.3 (q), 59.3 (d), 103.9 (d), 131.6 (d), 137.9 (d), 207.5 (s). Anal. calcd. for CI3H,,O3: C 69.61, H 8.98; found: C 69.25, H 8.89.

Diels-Alder reaction of 5 with I,3-cyclohexadiene. Forrnation of endo-5-acetyl-exo-6(2,2-dirnethoxyethyl)bicyclo- [2.2.2]oct-2-ene (9) and exo-5-acetyl-endo-G(2.2- dirnethoxyethyl)bicyclo[2.2.2]oct-2-ene (10)

Compound 5 (1.00g, 6.32 mmol) and 1,3-cyclohexadiene (6.6g, 100 mmol) were heated in a Carius tube as described above. High vacuum pumping (0.01 Torr) at 35-40°C removed most of the dimerized diene and chromatography (silica gel, 6:4 cyclohexane and ethyl acetate) of the residue afforded the endo and exo stereoisomers 9 and 10 (1.02g, 68%); the endo acetyl adduct (60% of the mixture) had the longer retention time. Compound 10: ir k,,,: 5.85 pm; 'H nrnr 6: 1.05-1.09 (m, 7H), 1.9-2.5(m,3H),2.19(~,3H),3.22(~,6H),4.25(t,J= 5Hz, lH), 6.00(m, 2H). Compound 9: irk,,,: 5.85 pm; 'H nmr 6: 1.05-1.09 (m, 7H), 1.9-2.5 (m, 2H), 2.12 (s, 3H), 2.78 (m, lH), 3.23 (s, 3H), 3.28 (s, 3H), 4.29(t, J = 5 Hz, lH), 6.14(m, 2H); 13C nmr 6: 18.4 (t), 26.4 (t), 28.3 (q), 33.2 (d), 34.5 (d), 37.7 (t), 52.6 (q), 53.1 (q), 58.8 (d), 104.4(d), 129.9(d), 136.6(d), 209.3 (s). Anal. calcd. for C14H2203: C 70.56, H 9.30; found: C 70.76, H 9.21.

Diels-Alder reaction of 5 with anthracene. Fortnation of trans-7-acetyl-8-(2,2-dimethoxyethyl)dibenzobicyclo- [2.2.2]octadiene (12)

Compound 5 (1.35g, 8.54 mmol) and anthracene (1.01 g, 5.68 mmol) were heated in a Carius tube at 150°C for 5 days. High vacuum pumping (0.01 Torr) at 50"Cfollowed by elution through a silica gel column (30 x 2 cm) with 7Wo hexane in ethyl acetate afforded the adduct 12 (1.48g, 77% based on consumed anthracene) as a viscous oil; ir A,,,: 5.83 pm; ' H nmr 6: 1.50 (m, 3H), 2.07 (s, 3H), 2.42 (m, lH), 3.19 (s, 3H), 3.25 (s, 3H), 4.12 (m, lH), 4.35 (m, lH), 4.44 (m, lH), 7.10 (m, 8H); I1C nrnr 6: 28.5 (q), 37.1 (d), 38.7 (t), 47.4 (d), 49.4 (d), 52.5 (q), 53.1 (q), 60.2 (d), 103.8 (d), 126.3-123.1 (7 signals), 139.2 (s), 141.05 (s), 142.5 (s), 143.8 (s), 207.1 (s). Anal. calcd. for C,2H,403: C 78.54, H7.19; found: C 78.56, H 7.44.

Diels-Alder reactiotl of 5 with I ,3-diphenylisobenzofuran. Fortnation of exo-2-acetyl-l,2,3,4-tetrahydro-endo-3- (2.2-dimethoxyethy1)-I ,4-epoxynaphthalene(l4) and endo- 2-acetyI-1,2,3,4-tetrahydro-exo-3-(2,2-dimethoxyethyl)- 1.4-epoxynaphthalene (15)

Compound 5 (1.00g, 6.32 mmol) and 1,3-diphenylisobenzofuran (1.70 g, 6.30 rnmol) were heated in boiling benzene (20 mL) for 72h. The solvent was removed and the oily residue was crystallized from hexane - ethyl acetate to give the exo-acetyl isomer 14 (2.01g, 74%), mp 103-105°C. The mother liquor contained the endo-acetyl isomer 15 together with a small amount of 14. Compound 15: irk,,,: 5.92,6.23 (w) pm; 'H nmr 6: 1.70(~,3H),l.45-2.2(m,2H),2.80(m, lH),3.17(~,6H),3.70 (m, lH), 4.25 (m, lH), 7.40 (m, 14H). Compound 14: ir A,,,: 5.92, 6.23 (w) pm; IH nmr 6: 0.55-1.0 (rn, lH), 1.92 (s, 3H), 1.8-2.2(m, lH),2.85(d, J = 4.5Hz, lH), 3.1-3.4(m, lH),3.25 (s,6H),4.2-4.4(m, lH),7.45(m, 14H); 13Cnmr6:27.2(e),35.9 (t), 45.6 (d), 53.5 (q), 53.7 (q), 67.7 (d), 89.8 (s), 90.7 (s), 103.6 (d), 118.4 (d), 121.6 (d), 128.6-125.8 (7 signals), 136.2 (s), 136.3 (s), 144.8 (s), 148.2 (s), 209.1 (s). Anal. calcd. for Cz8H2,04: C 78.48, H 6.59; found: C 78.48, H 6.59.

Hydrolysis of 6, 9, and 12. Forrnation of the keto aldehydes 8, 11, and 13

A mixture of the acetal(5 mmol), tetrahydrofuran (5 mL), and 1.2 N hydrochloric acid (5 mL) was stirred under nitrogen a t

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room temperature for ca. 10h. Addition of water (10 mL) followed by extraction with dichloromethane (3 x 5 mL), washing of the extract with aqueous 5% sodium bicarbonate, drying, and removal of the solvent gave the keto aldehydes in quantitative yield.

endo - 6-Acetyl- exo-5-(2-oxoethyl)bicyclo[2.2. Ilhept-2- ene (8): irk,,,: 3.63 (w),5.81, 8.85 pm; IHnmr6: 1.5-7.5(m, 3H), 2.15(~,3H),2.5-2.8(m,4H),3.21(m, lH) ,5 .85(dd,J=3,6Hz, lH), 6.22 (dd, J = 3, 6 Hz, lH), 9.74 (t, J = 2 Hz, 1H). Anal. calcd. for C, ,H,,02: C 74.13, H 7.92; found: C 73.92, H 8.00.

endo- 6-Acetyl- exo - 5-(2-oxoethyl)bicyclo[2.2.2]oct-2-ene (11): irk,,,: 3.64(w),5.80,5.85pm; lHnmr6: 1.1-1.9(m,5H), 2.15(~,3H),2.3-2.6(m,4H),2.85(m,lH),5.9-6.6(m,2H),9.75 (t, J = 2 Hz, 1H). Anal. calcd. for C l2HI6o2 : C 74.97, H 8.39; found: C 74.48, H 8.33.

trans-7-Acetyl-8-(2-oxoethyl)dibenzobicyclo[2.2.2]octadiet~e (13): irk,,,: 3.64(w), 5.81,5.83(sh) pm; IHnmr6: 1.23(m, lH), 2.15 (s, 3H), 2.20 (m, 3H), 4.16 (d, J = 2 Hz, lH), 4.44 (d, J = 2 Hz, lH), 7.12(m, 8H), 9.64(t, J = 1 Hz, 1H).

Treatment of 14 with 90% formic acid. Formation of 4-acetyl- 2,3-3a,4,5,9b-hexahydro-5,9b-diphet~ylnaptho[l,2-b]- frtran-2,5-diol ( I 7)

A solution of 14 (0.250g, 0.853 mmol) in aqueous 90% formic acid (15 mL) was allowed to stand under nitrogen at room temperature for 2 h. The mixture was diluted with water (20 mL) and extracted with dichloromethane (3 x 5 mL). Crystallization of the oily residue from hexane - ethyl acetate yielded the tricvclic hemiacetal 17 as colorless orisms (0.201 e. 86%). mo 1911192"~; irk,,,: 2.80(w), 2.95(m):5.95,6..26(w)cim; l ~ n m ; 6: 1.4-2.3(m, 2H), 1.90(s,3H),3.31 (dd, J = 6,12Hz, 1H),3.98 (m, 1H; absent after D 2 0 treatment), 4.38 (d, J = 12 Hz, lH), 4.63 (s, 1H; absent after D 2 0 treatment), 5.75 (dd, J = 3 , 5 Hz, 1H; d, J = 5 Hz, after D 2 0 treatment), 6.6-7.8 (m, 14H); I3C nmr 6: 34.4 (q), 35.6 (t), 44.3 (d), 58.0 (d), 76.4 (s), 88.4 (s), 98.8 (d), 125.8-147.4 (13 signals), 216.8 (s). Anal. calcd. for C2,H2,- 0,: C 77.98, H 6.04; found: C 77.72, H 6.05.

Attetnptedintramolecular aldol condensatiot~ ofketo aldehydes 8, 11, and 13

I 'The conditions tried included treatment with the following I reagents under the conditions indicated: aqueous 10% potas-

sium hydroxide in methanol (12) with stimng at room temperature, M C , and at reflux; potassium hydroxide in b o h g aqueous tetrahydrofuran ( 13, 14a); increasingly concentrated aqueous potassium hydroxide (5, 10, 15, and 20%) in equal volumes of methanol; a catalytic amount of piperidinium acetate in benzene (146) at room temperature; methanolic tetramethylammonium hydroxide at 60°C; an excess of aluminum tert-butoxide in boiling benzene (14c); a catalytic amount of potassium tert- butoxide in boiling tert-butyl alcohol; potassium carbonate in boiling methanol (14d); a catalytic amount of anhydrous para- toluenesulfonic acid in boiling benzene ( 1 5 ~ ) ; hydrochloric acid, water, and tetrahydrofuran (156) with stimng at room temperature and at reflux.

Irradiation of (E)-6,6dimethoxy-3-hexen-2-one (5). Formation of (Z)-6,6dimethoxy-3-hexen-2-one (21)

A solution of 5 (0.160g, 0.010 mol) in benzene (100 mL) was degassed by bubbling nitrogen from a fine capillary tube through the length of a 40 x 5 cm quartz tube for 1 h. The tube was sealed and irradiated in a Rayonet photochemical reactor (330 nm) for 6 h. Benzene was removed and the resulting oil was molecularly distilled togive a - 5050 mixture of 21 and 5 (92%); ir A,,,: 5.93, 6.12 (m), 7.35 (w) pm; 'H nmr 6 (21 only): 2.10(s, 3H), 2.95 (m, 2H), 3.33 (s, 6H), 4.45 (t, J = 6 Hz, lH), 6.20 (m, 2H).

Treatment of 6 and 7 ~vith p-toluet~es~rlfonic acid. Fortnation of 3-acetyl-9-t~1ethoxytetracyclo[4.3.0.0~~~.O~~~]tzonane (27)

A solution of 6 and 7 (0.508g, 2.26 mmol) and anhydrous p-toluenesulfonic acid (0.60g, 0.31 mmol) in dry benzene (25 mL) was boiled under reflux for 1 h. The solution was diluted with water (10 mL) and extracted with ether (4 x 5 mL) and the organic phase was concentrated, yielding a black oil. This was triturated with a small amount of hexane - ethyl acetate (7:3) which separated insoluble, polymerized material. The solution was concentrated and chromatographed (silica gel. 7:3 hexane and ethyl acetate) and yielded fosilate 28 as an dil (0.1421 g, 18%) and the tetracyclic ketone 27 (0.0925g, 2 1%) as a colorless oil which was molecularly distilled at 44.5OC (0.065 Torr). Compound 28: ir A,,,: 5.86, 6.23 (w) pm; 'H nmr 6: 1.2-2.5 (m, 9H), 2.07 (s, 3H), 2.44 (s, 3H), 3.14 (s, 3H), 3.60 (m, lH), 4.14 (m,lH),7.32(d,J=8Hz,2H),7.26(d,J=8Hz,2H);l3Cnrnr 6: 21.7, 28.8, 33.5,40.4,40.7,44.0,45.0,54.3, 56.8, 59.1, 85.9, 88.1, 127.6, 129.8, 134.2, 144.7, 206.2. Compound 27: ir A,,,: 5.90,9.90 (w) pm; IH nmr 6: 1.38 (m, lH), 1.67 (m, 3H), 1.97 (s, 3H), 2.10(m, 2H), 2.29(m, 3H), 3.24(s, 3H), 3.61 (m, 1H); I3C nmr6: 27.0(q), 27.6(d), 29.4(d), 31.1 (t), 35.8 (t),40.8(d),42.0 (d), 48.8 (d), 56.1 (q), 81.7 (d), 206.5 (s). Anal. calcd. for C l2HI6o2 : C 74.97, H 8.39; found: C 74.77, H 8.46.

Acknowledgement We thank the Natural Sciences and Engineering

Research Council of Canada for support of this work.

1. J . C. SAUER. Org. Synth. Coll. Vol. IV, 813 (1963). 2. A. P. SKOLDINOV, A. P. ARENDARUK, and G. M. GOD-

ZHELLO. J . Org. Chem. U.S.S.R. 6,421 (1970). 3. L . J. BELLAMY. The infra-red spectra o f complex mole-

cules. 2nd ed. Methuen, London. 1958. pp . 45-49. 4. L . M. JACKMAN and S. STERNHELL. Applications of

nuclear magnetic resonance spectroscopy in organic chem- istry. 2nd ed. Pergamon, New York. 1969. pp. 230-232.

5. J . C. DAVIS, JR. and T. V. VAN AUKEN. J. Am. Chern. Soc. 87,3900 (1965).

6. P. LASZLO and P. v. R. SCHLEYER. J . Am. Chem. Soc. 86, 1171 (1964).

7. J. R. L. SMITH, R. 0. C. NORMAN, and M. R. STILLINGS. Tetrahedron, 34, 1381 (1978).

8. H . WOLLWEBER. Diels-Alder-Reaktion. Georg Thieme Verlag, Stuttgart. 1972. p. 14.

9. R. R. FRASER and S. O'FARELL. Tetrahedron Lett. 1143 (1 962).

10. M. A. BATTISTE and C . T. SPROUSE. JR. Tetrahedron Lett. 4661 (1970); R. BRESLOW, G. RYAN', and J. T. GROVES. J. Am. Chem. Soc. 92,988 (1970).

11. A. GORGUES. Bull. Soc. Chim. Fr. 529 (1974). 12. W. F. JOHNS. J. Org. Chem. 26,4583 (1961). 13. J . DAS, R. KUBELA, G . A. MACALPINE, Z. STOJANAC, and

Z. VALENTA. Can. J. Chem. 57, 3308 (1979). 14. (a) J . MATSUDA, S. MURADA, and Y. IZUMI. J . Org. Chem.

45, 237 (1980); (b) G. STORK, E. E. VAN TAMELEN, L. J. FRIEDMAN, and A. W. BURGSTAHLER. J. Am. Chern. Soc. 75,384(1953); (c) B. M. T ~ o s ~ a n d W. C. VLADUCHICK. J. Org. Chem. 44, 148 (1979); (d) G. GORMELY, JR., Y. Y. CHAN, and J. FRIED. J. Org. Chem. 45, 1447 (1980).

15. (a) S. W. BALDWIN and J . M. WILKINSON. J. Am. Chem. Soc. 102, 3634 (1980); (b) R. E. ABBOTT and T. A. SPENCER. J. Org. Chern. 45, 5398 (1980).

16. F. RAMIREZ and S. DERSHOWITZ. J. Org. Chem. 22, 41 (1957).

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