The dienone–phenol rearrangement. Synthesis of spiro4.5dec-7-ene-6,9-dione

摘要

964 J.C.S. Perkin IThe Dienone-Phenol Rearrangement. Synthesis of Spiro4.5dec-l-ene-6,g-dioneBy Randy1 G. A. Flynn and Paul D. Woodgate,' Chemistry Department, University of Auckland, New ZealandSpiroC4.51 dec-7-ene-6.9-dione (11) has been synthesized and identified as one component of the mixture formedon rearrangement of 6-hydroxybicyclo 4.4.0 deca-1.4-dien-3-one catalysed by boron trifluoride-ether complex.PREVIOUS work on the rearrangement of 6-hydroxy-bicyclo4.4.0deca-l,4-dien-3-one (I) catalysed by borontrifluoride-ether complex resulted in the identification0 0( I 1 (II) rm,of a neutral product as spiro4.5dec-7-ene-6,9-dione (11),this being the first reported isolation of a spiran inter-mediate from a dienone-phenol type rearrangement .2The structural assignment was based on the i.r., lHn.m.r., and mass spectra of (11) and its dihydro-derivative, spiro4.5decane-6,9-dione (111). However,since (11) was not isolated in a pure state and was anunknown compound, we undertook its unambiguoussynthesis to confirm our identification.The synthesis involved spiroannulation of cyclo-hexanone to produce spiro4.5decan-6-one (IV) , intro-duction of the 7,8-double bond by sequential bromin-ation and dehydrobromination, functionalization of theallylic C-9 position, and subsequent manipulation toproduce the desired oxidation level.The parent spiro-compound (IV) was synthesized 3 byreaction of the enolate of cyclohexanone with 1,4-G.I?. Burkinshaw, B. R. Davis, E. G. Hutchinson, P. D.Woodgate, and R.Hodges, J . Chem. SOC. ( C ) , 1971, 3002.For reviews see,A. J. Waring, Adv. Alicyclic Chem., 1966,1 ( 3 ) ; B. Miller in Mechanisms of Molecular Migration,' ed.B. S. Thyagaragan, Interscience, New York, 1968, p. 247.dibromobutane, and was isolated in 49 yield byspinning-band distillation. Preparative t.1.c. of thedistillation residue give the bis-annulation product,dispiro4.1.4.3tetradecan-6-one (V) in 24y0 yield.Bromination of (IV) was initially attempted withpyridinium hydrobromide perbromide. This reagenthas been used successfully to produce mono-a-bromo-ketones4 as it can be readily weighed out to liberate acm,precise (equimolar) amount of bi-oiiiiiie, thereby prevent-ing formation of the act-dibromo-derivative. In theevent, however, both 7-bromospiro4.5decan-6-one(VI) and 7,7-dibromospiro4.5decan-6-one (VII) wereformed.Treatment of the crude bromination productwith lithium bromide-lithium carbonate in dimetliyl-M. Mousseron, K. Jacquier, and H. Cristol, Bull. SOC. chilit.FJtancc?, 1957, 346.C. Djerassi and C. R. Scholz, J . .49nev. Chem. SOC., 1948, 70,417.Ia) Cm)exhibited characteristic ap-unsaturated carbonyl ab-sorptions at 1665 cm-l in the i.r.spectrum and at 227 nm(log E 3.79) in the U.V. spectrum. The i.r. spectrum ofthe bromo-enone (IX) showed a characteristic a-halogeno-@-unsaturated carbonyl peak at 1685 cm-l,and the 8-proton signal appeared in the lH n.m.r.spectrum as a triplet ( J 4 Hz) at 8 7.15.The co-production of the bromo-enone (IX) wassubsequently avoided by treating a solution of thespiro-ketone (IV) in tetrahydrofuran with bromine indichloromethane ; under these (non-basic) conditionsthe desired bromo-ketone (VI) was formed in quanti-tative yield. Its i.r. spectrum displayed carbonylabsorptions at 1727-5 and 1704.5 cm-l, correspondingto the equatorial and axial bromine conformers, re-spectively. Dehydrobromination of crude 7-bromospiro-4.5decan-6-one was best achieved by treatment withmagnesium oxide in dimet hylformamide under nitrogenat 120-140°.6 Spinning-band distillation of the totalproduct gave pure spiro4.5dec-7-en-6-one (VIII) in58 yield.The use of 1 ,5-diazabicyclo4.3.0non-5-enein refluxing benzene or in dimethylformamide at 100-110" also afforded (VIII) but in lower yields (27 and39 , respectively) .Attempted direct allylic oxidation of the enone (VIII)to the enedione (11) with either sodium chromate inacetic anhydride-acetic acid 7 or cerium( IV) ammoniumnitrate in acetic acid-water8 gave a complex mixture(t.1.c.) which was not further investigated, and aftertreatment of (VIII) with selenium dioxide in dimethylsulphoxideQ for 40 h more than 90 of the startingmaterial was recovered.It was therefore necessary toemploy a longer route to the desired compound. Re-action of unrecrystallized N-bromosuccinimide with theM. Rfiyano and C. R. Dorn, J. Ovg. Chem., 1972, 37, 268. ' J. A. Marshall and G. M. Cohen, J. Org. Chem., 1971,36, 877. * W. S. Trahanovsky and L. B. Young, J. Chem. SOC., 1965,5777.enone (VIII) in dry carbon tetrachloride afforded9-bromospiro4.5dec-7-en-6-one (X) in 57 yield afterpreparative t.1.c. Spectral absorptions at 1680 cm-l inthe i.r. and at 221 nm (log E 3.77) in the U.V. were in theexpected regions. In the lH n.m.r. spectrum virtualcoupling between the C-8 vinyl proton and the C-10methylene protons was demonstrated by irradiation ofthe C-9 proton signal, which caused the C-8 protonpattern to collapse to a clean doublet (J8,, 10.4 Hz).If the C-10 methylene protons and the C-9 methineproton are considered as an isolated ABX system, thenear equality of the observed Jssl0 values (7.6 and7-0 Hz) in conjunction with the appearance of two sharpsignals integrating for two protons at 6 2.40 and 2.50indicates that the observed pattern represents adeceptively simple spectrum due to (VA - VB) tending to0.Hence the real J values cannot be extracted by asimple first-order analysis. Nevertheless, the fact thatthe C-7 proton signal is split by coupling through to theC-9 proton allows the conclusion that this allylic torsionangle must be close to 90". Consequently, the moleculemust assume a dominant conformation such that thebromine atom is equatorial, as would be anticipatedfrom steric considerations (space-filling model).Attempted displacement of the bromine atom in (X)with lithium carbonate in either dioxan-water ordimethyl sulp hoxide-water afforded a seven-componentmixture.However, the bromo-enone was convertedinto 9-acetoxyspiro4.5dec-7-en-6-one (XI) by treatmentwith silver acetate in acetone a t room temperature.The i.r. and U.V. spectra showed the expected features,and in the lH n.m.r. spectrum a broad (W, 20 Hz) signalcentred at 8 5-72 attested to the predominantly axialorientation of the C-9 proton. The allylic acetate (XI)was hydrolysed by heating under reflux in methanol-water with a catalytic amount of sodium carbonate,preparative t .l.c. then yielding pure 9-hydroxyspiro-4.5dec-7-en-6-one (XII). Finally, spiro4.5dec-7-ene-6,g-dione (11) was obtained in 58 yield by oxidationof the allylic alcohol (XII) with manganese dioxide.Attempted oxidation of (XII) with silver carbonate-Celite lo returned starting material after heating underreflux for 7 h. The synthetic compound (11) wasidentical (i.r. and lH n.m.r. spectra; t.1.c.) with asample previously obtained from rearrangement of the9-quinol (I). Moreover, reduction of synthetic (11) withzinc-acetic acid afforded spiro4.5decane-6,9-dione (111) ,which showed identical spectral properties and nodepression of m.p. with a sample obtained from therearrangement product.This synthesis therefore con-firms our previous assignment and provides unambiguousevidence for the existence of a spiran intermediate inthe rearrangement of the $-quinol (I).The 70 eV mass spectra of all the spiro-compoundsreported above contained an intense peak, often theS A. N. Singh, A. B. Upadhye, M. S. Wadia, V. V. Mhaskar,10 M. Fetizon, M. Golfier, and J. Louis, Chem. Comm., 1969,and S. Dev, Tetrahedron, 1969, 25, 3855.1102966 J.C.S. Perkin 1base peak, whose formation can be rationalized by aMcLafferty rearrangement of a y-hydrogen atom fromthe cyclopentane ring, followed by allylic cleavage.Conformational Analysis of the Bvomo-ketone (VI) .-The carbonyl absorptions at 1727.5 and 1704.5 cm-l arisefrom the bromine-equatorial and bromine-axial con-formers, respectively.By studying the variation withtemperature of the relative areas of these peaks (Table)TABLE a ~ bT/K 258 273 288 303 318 333 34sAhe 77 70 65 64 60 57 34-did 23 22 22 23.5 24 23 23.54 These data were measured with CCl, as solvent by Dr. G . D.Meakins, University of Oxford, using an analogue computermethod of curve resolution. b A = : area; expressed so thatA h + A, = 100 at 268 I. Campbell,University of Otago, New Zealand. 1.r. spectra weremeasured for thin films on a Perkin-Elmer 237 spectrometer.1H N.m.r. spectra were measured for solutions in CDC1, orCCl, on a Varian T60 spectrometer: J(apparent) values arereported for non first-order signals.Assignments wereconfirmed by double resonance where practicable.Spivo4.5decan-6-one (IV) .9-A mixture of cyclohexanone(9.6 g) and 1,4-dibromobutane (21.6 g) was added to astirred suspension of potassium t-butoxide (21.9 g ) inl1 D. J. Chadwick, J. Chambers, G. D. Meakins, and R. L.Snowden, J.C.S. Perkin I I , 1972, 1969.benzene (150 ml). The mixture was heated under refluxfor 4-5 h and the product was extracted into ether; usualwork-up followed by spinning-band distillation gave purespiro4.5decan-6-one (8.6 g, 57y0), b.p. 96" at 20 mmHg(lit.,a 104" a t 18 mmHg), v- 1709 cm-', 6 1-24-2.75.The distillation residue was subjected to column chro-matography on silica gel (200 ml) with n-hexane-ether(99: 1) as eluant.The eluates were further purified bypreparative t.1.c. (n-hexane-ether, 99 : 1 ; two passes) t ogive dispi~o4.1.4.3te~radecun-6-one (V) (0.5 g, 2.4y0), m.p.32-34" (Found: C, 81.3; H, 10.7. C1,H2,0 requires C,81.5; H, 10.7), vmaL (CCl,) 1693 cm-l, 6 1-20-2.20.S~zro4.5dec-7-en-Ci-one (VIII) .-(u) A solution of bro-mine (21-1 g) in dichloromethane (25 ml) was added drop-wise to a cooled (ice-bath), stirred, solution of spiro4.5-decan-6-one (20 g ) in tetrahydrofuran (180 ml). Stirringwas continued for 10 min after addition was complete ( 1 11).Aqueous NaHCO, solution was then added and the mixturewas stirred until effervescence ceased. Work-up thenafforded crude 7-bromospiro4.5decan-6-one, a smallportion of which was purified by column chromatography(10 deactivated silica gel) and then repeated crystalliz-ation from n-pentane to give flakes, m.p.48-41" (lit.,551-55'), vmar 1727.6 and 1704.5 crn-l, 6 1.18-2-59 (14H,m, 7 x CH,) and 4-62 (lH, X part of ABX, JAx + JBx16 Hz, C-7 proton).The crude bronio-ketone dissolvecl in dimethylformamide(25 ml) was added under nitrogen to a stirred suspension ofmagnesium oxide (6-9 g ) in dimethylformamide (250 ml)which had been pre-heated to 120-140", and the mixturewas stirred a t this temperature for 1 h. After cooling,water (80 ml) and aqueous HCI (loo,; 200 nil) were added,and the solution was extracted with ether. Spinning-banddistillation of the crude product obtained after work-upgave pure (g.1.c.) spiro4.5Jdec-7-en-6-one (1 1.4 g, 58),b.p. 119" a t 22 mmHg, vmt 1665 and 1620 cm-1, = 227(log E 3.79) and 324 nm (log z 1-56), 6 1.18-1.98 (lOH, m,5 x CH,), 2.02-2.54 (2H, m, C-9 protons), 5.85 (IH, 2t,J7,* LO, J7,,, 2 Hz, C-7 proton), and 6-75 (lH, 2t, Je,7 10,J8,B 4, J8.,, 4 Hz, C-8 proton).The 2,4-dinitrophenyl-Jzydrazone had m.p. 133-134.5" (from methanol) (Found:C, 58.1; H, 5.4; N, 16.75. C1,H,,N404 requires C, 58.2;H, 5.5; N, 16.95).( b ) Pyridinium hydrobromide perbromide (10 g) wasadded during 20 min to a solution of spiro4.5decan-6-one(4.76 g) in acetic acid (50 ml). Work-up as usual followedby chromatography on silica gel (120 i d ; 10 deactivated)with n-hexanc-ether (49: 1) as eluant afforded pure 7-bromospiro4.6decan-6-one (5.8 g, 78).Dehydrobromination of the crude product with lithiumbromide (11.4 g) and lithium carbonate (9 g) in dimethyl-formamide (90 ml) followed by preparative t.1.c.(benzene)yielded spiro4.5dec-7-en-6-one (2.34 g , 50) and 7-bromo-spiro4.5dec-7-en-6-one (0.5 g, 7), vmax. 1685 and 1605 cm-l,6 1.13-2.55 (12H, m, 6 x CH,) and 7-15 (IH, t, Je,B 4 and4 Hz, C-8 proton).9-Brornos~i~o4.5~~-7-en-6-one (X) .-AT-Bromosuccin-imide (1.45 g; not recrystallized) was added to a solution ofspiro4.5dec-7-en-6-one (1.02 g) in dry carbon tetra-chloride (50 ml) and the mixture was heated under refluxfor 7 h. Work-up gave a yellow oil which was purified byI* E.J. Corey, T. H. Topie, and W. A. Wozniak, J . Amev.Chem. SOC., 1966, 77, 6416.E. W. Garbisch, J. Amev. Chem. SOC., 1964, 86. 1780.E. W. Garbish, J . Ovg. Chem., 1966, 30, 21091974 967preparative t.1.c. (benzene) to give pure 9-brof?mpzro4.5-dec-7-en-6-one (0.88 g, 57) as an oil (Found: C, 52-5; H,5.6; Br, 34.4. CloH,,BrO requires C, 52.4; H, 5-7; Br,34.8), vmpx. 1680 cm-l, Amax. 221 nm (log E 4-02), 6 1.10-2.35 (8H, m, 4 x CHA, 2.40 and 2.50 (2H, 2 ' s', C-10protons), 4.90 (lH, 4q, Je,lo 7.6 and 7-0, Je,a 2.8, JSs7 1.9 Hz,C-9 proton), 5.82 (lH, 2d, J7,8 10.4, J 7 , g 1.9 Hz, C-7 proton),and 6.85 (lH, 4t, J8,7 10, J 8 , 9 2.8, Js,lo 0.6 and 0.6 Hz, C-8proton).9-A cetoxys~iro4.5dec-7-en-6-one (XI) .-Silver acetate(0.29 g) was added to a solution of 9-bromospiro4.5dec-7-en-6-one (0.20 g) in acetone (10 ml) and the mixture wasstirred at room temperature for 64 h.Filtration andevaporation of the filtrate at ambient temperature in vac2aogave a yellow oil. Preparative t.1.c. (benzene-acetone, 9 : 1)afforded pure 9-acetoxyspiro4.5dec-7-en-6-one (0.09 g , 50)as an oil (Found: C, 69.35; H, 7-5. C,,H,,O, requires C,69.25; H, 7-7), vmax. 1745, 1678, and 1629 cm-l,221 nm (log E 3-90), 6 1.05-2.02 (8H, m, 4 x CH,), 2.10(3H, s, acetate), 2-18-2-89 (2H, ni, C-10 protons), 5-72( 1 K 4 Jg.10 9, J e . 1 0 6, J 9 . 8 2.5, J g . 7 2.2 Hz, c-9 proton),6-02 (lH, Zd, J 7 , 8 10.4, J7,9 2.2 Hz, C-7 proton), and 6.77(1H, 2q, J8., 10-4,9-Hydroxyspiro4.5dec-7-en-6-o.~ze (XII) .-Sodium car-bonate (3 mg) was added to a solution of 9-acetoxyspiro-4.5dec-7-en-6-one (40 mg) in 50 aqueous methanol(10 ml) and the solution was heated under reflux for 40min.After removal of the solvent in vacuo the residue was2.5, J8,10 1.3 Hz, C-8 proton).salted (NaC1) and extracted with ether. Preparative t.1.c.(benzene-acetone, 9 : 1) yielded pure 9-hydroxyspiro4.5)-dec-7-en-6-one (10 mg, 35) as an oil, Mf' 166, v- 3440,1670, and 1622 cm-l, 220 nm (log E 3-72), 6 1.24-2.54(11H, m, 5 x CH, and OH), 4-62 (lH, 4t, Jg,lo 10, Je,lo 6,Je,8 2, J e , , 2-2 Hz, C-9 proton), 5-92 (lH, 2d, J 7 , 8 10.3,J7,9 2.2 Hz, C-7 proton), and 6-85 (lH, 2t, J8,7 10.3, Jaee 2,Jssl0 2 Hz, C-8 proton).S~iro4.5dec-7-ene-6,9-dione (11) .-Treatment of a solu-tion of 9-hydroxyspiro4.5dec-7-en-6-one (50 mg) in benz-ene (50 ml) with manganese dioxide (40 mg) at room tem-perature for 10 min gave, after purification by preparativet.1.c. (benzene-acetone, 9 : l), spiro4.5dec-7-ene-6,9-dione(30 mg, 56), m.p. 38-41" (Found: C, 73.0; H, 7.55.C,,HI,O, requires C, 73.2; H, 7-4), vm= 1682 and 1608cm-l, hTC 226 nm (log E 3-99), 6 1.0-2-4 (SH, m, 4 x CH,),2-80 (2H, s, C-10 protons), and 6.71 (2H, s, C-7 and C-8protons).Spiro4.5 decane- 6,g-dione. -Reaction of spiro 4.51 d ec- 7-ene-6,g-dione (30 mg) with zinc (0.1 g ) in acetic acid (4 ml)at room temperature afforded, after work-up, spiro4.5-decane-6,g-dione (20 mg, 86), m.p. 89-91' (from n-pentane-ether) (lit.,l 88.5-89-5°), undepressed on ad-mixture with the sample previously obtained ; 1 vmu.1710 cm-l, 6 1.18-2.30 (8H, m, C-1, C-2, C-3, and C-4methylene protons) and 2.65-2-76 (GH, m, C-7, C-8, andC-10 methylene protons).3/2306 Received, 9th November. 1973