J . Org. Chem. 1987,52, 4943-4953 calcd for CllHIOSS301.9386,obsd 301.9383. Recently it has been found that trituration of a mixture of 21 and 22 with pentane and chilling at -20 "C gives pure crystalline 22. Removal of the pentane under reduced pressure gives 21.
Preparation of 2-Phenyl-ex0-3,4,5-trithiatricyclo[5.2.l.O2v6]decane(24) (Table 11, Line 11). Repetitive trituration with pentane and chilling at -20 "C gave a solid: mp 54-56 "C; 'H NMR 6 5.30 (m, 5 H), 4.00 (d, J = 2.0 Hz, 1 H), 3.20 (s, 1 H), 2.48 (d, J = 10.8 Hz, 1 H), 2.38 (s, 1 H), 1.60 (m, 2 H), 1.40 (m, 1 H), 1.30 (d, J = 10.8 Hz, 1 H),1.05 (m, 1 H); 13C NMR 143.2 (s), 127.6,126.8 (3C), 86.9 (s), 69.3 (d), 45.1 (d), 42.1 (d), 33.9 (t), 27.3 (t),24.4(t)ppm; IR (neat) 3050,2950,2850,166C-1940 (weak overtones), 1590,1480,1460,1440,1300,1160,1025,900,750,700, 640 cm-'; mass spectrum, m / e calcd for C13H14S3266.0257,obsd 266.0249;M , calcd 266, obsd 264. Preparation of 2-p -Anisyl-exo -3,4,5-trithiatricyclo[5.2.1.02s6]decane(25) (Table 11, Line 12). 26 (380 mg, 65%) was isolated as a yellow oil: 'H NMR 6 7.20 (m, 2 H),6.83 (m, 2 H), 3.95 (d, J = 2.0 Hz, 1 H), 3.80 (s, 3 H), 3.20 (s, 1 H), 2.50 (d, J = 10.8 Hz, 1 H), 2.38 (s, 1 H), 1.30-1.75 (s of m, 3 H), 1.25 (d, J = 10.8 Hz, 1 H),1.10 (m, 1 H); 13C NMR 158.43 (s), 135.49 (s), 128.36 (d), 115.24 (d), 86.92 (s), 69.46(d), 55.20 (q), 45.32 (d), 42.19 (d), 34.09 (t),27.37 (t),24.40 (t)ppm; IR (neat) 3025,2950, cm-'; MS (70eV), 1600,1500,1450,1260,1180,1030,900,820,740 Mt not observed, m l e 200 (30%) was observed indicating immediate loss of sulfur followed by a loss of ethylene to give m l e 172 (100%). Anal. Calcd for C14H160S3: c, 56.8;H, 5.4;s,32.4. Found: C, 56.8;H, 5.7;S,32.7. Preparation of 1,2,3,4,9,10-Hexahydro-9,lO-exo -epoxy-l,4-
exo-methano-4a,9a-exo-trithiaanthracene (29) (Table 11, Line 13). Chromatography over silica gel with pentane/Et20 (65:35)as eluant gave 20 mg of 29 as a viscous oil, yield 46%: 'H NMR 6 7.35 (m, 2 H), 7.20 (m, 2 H), 5.60 (s, 2 H), 3.15 (d, J = 10.4 Hz, 1 H), 2.58 (m, 2 H), 1.25 (m, 2 H), 1.10 (d, J = 10.4 Hz, 1 H), 0.75 (m, 2 H); I3C NMR 147.18 (s), 126.51 (d), 121.90 (d), 91.84 (s), 91.53 (d), 45.75 (t),46.41 (d), 22.88 (t) ppm; IR (neat) 3005,2900,1640,1450,1320,1200,900,720 cm-'; mass spectrum, m l e calcd for C15H140S3306.0206, obsd 306.0201. Preparation of 1,2,3,4,9,1O-Hexahydro-1,4-exo-methano9,10-exo-methano-4a,9a-exo-trithiaanthracene (33) and
4943
1,2,3,4,9,10-Hexahydro-1,4-exo-methano-9,lO-endo -methano4a,9a-exo-trithiaanthracene (34). A mixture of 31 and 32 (200 mg, 1 mmol) (38139 = 2.0) and 150 mg (4.7mmol) of sulfur in 8 mL of DMSO was heated at 100 OC under an atmosphere of N2for 8 h. The reaction mixture was poured into 20 mL of ice-cold water. This was then extracted twice with 15 mL of ether. The ethereal layer was washed with brine and dried over Na2S04. The crude, obtained after removal of the ether under reduced pressure, was chromatographed over silica gel by using CCl,/petroleum ether (4:l)as eluant, to give 20 mg of 34 and 50 mg of 33. Total yield of 33 and 34 was 23%. For 34 (Rf0.39): 'H NMR 6 7.00 (m, 2 H), 6.90 (m, 2 H), 3.40 (9, 2 H), 2.80 (d, J = 10.3 Hz, 1 H), 2.70 (s, 2 H), 2.50 (d, J = 11.2 Hz, 1 H), 1.90 (d, J = 11.2Hz, 1 H), 1.70 (m, 4 H), 1.20 (d, J = 10.3Hz, 1 H); 13CNMR 147.44,125.63,123.70,89.59,52.07,50.63, 47.69,43.69,24.43 ppm; IR (CC14)3080,1450,1260,970cm-'; mass spectrum, m / e calcd for C16H16S3304.0414,obsd 304.0413. For 33 (Rf0.53):'H NMR 6 7.20 (m, 2 H), 7.05 (m, 2 H), 3.90 (d, J = 9.8 Hz, 1 H), 3.70 (s, 2 H), 3.25 (d, J = 10.3 Hz, 1 H), 2.70 (s, 2 H), 1.85 (d, J = 9.8 Hz, 1 H), 1.10 (d, J = 10.3 Hz, 1 H), 0.85 (m, 4 H); 13CNMR 148.18,125.70, 123.10,93.20,59.39,56.63,49.64, 45.63,24.65ppm; IR (neat) 3000,1450,1260,900,750 cm-'; mass spectrum, calcd for C16H16&304.0414,obsd 304.0417. Both 33 and 34 when left for extended periods of time at room temperature became glassy solids, insoluble in CDC1,.
Acknowledgment. We thank the Robert A. Welch Foundation for support of this work. We are grateful to Professor Shigeru Oae for suggesting the initial experiments. Supplementary Material Available: Tables of 'H NMR chemical shifts in the trithiolanes and pentathiepanes, significant 'H and 13C chemical shifts for 5 and 6, and NMR and MS data of polysulfides obtained in the sulfuration of norbornadiene (3 pages). Ordering information is given on any current masthead page.
Construction of Five-Membered Rings by Michael Addition-Radical Cyclization Derrick L. J. Clive,* Taryn L. B. Boivin, and A. Gaetan Angoh Chemistry Department, University of Alberta, Edmonton, Alberta, Canada T6G 2G2 Received M a r c h 4,1987
Enamines react with Michael acceptors 8-10 to produce ketones that, on treatment with lithium acetylides, afford hydroxy acetylenes 3. These compounds then undergo radical cyclization when treated with triphenyltin hydride and AIBN. The products 6 are formed by 5-exo-digonal closure and furnish substituted cyclopentanones by ozonolysis.
Until recently, most procedures used in synthesis for making carbon-carbon bonds were based on ionic or concerted reactions, and the possibility of using free radicals was not widely recognized-at least outside the area of polymer chemistry.' This situation is now changing, and free-radical methods2 for making carbon-carbon bonds (1)For early, isolated examples of the synthetic use of radicals to make carbon-carbon bonds, see: (a) Bakuzis, P.; Campos, 0. 0. S.; Bakuzis, M. L. F. J.Org. Chem. 1976,41,3161.(b) Buchi, G.; Wuest, H. Ibid. 1979, 44,546. See also: Julia, M. Acc. Chem. Res. 1971,4,386.
will, undoubtedly, come to occupy an important place in organic synthesis. There already exists extensive modern literature2v3 on intermolecular reactions (e.g., eq 1, A = electron-withdrawinggroup), and there is a rapidly growing i n t e r e ~ t ~in, ~the , ~synthetic utility of intramolecular cy(2) Giese, B. Radicals in Organic Synthesis: Formation of CarbonCarbon Bonds; Pergamon: Oxford, 1986. (3)Giese, B. Angew. Chem., Int. Ed. Engl. 1983,22,753. (4) (a) Hart, D.J. Science (Washington, D.C.)1984, 223, 883. (b) Surzur, J.-M. In Reactiue Intermediates; Abramovitch, R. A., Ed.; Plenum: New York, 1982;Chapter 3.
0022-3263/87/1952-4943$01.50/00 1987 American Chemical Society
4944 J . Org. Chem., Vol. 52, No. 22, 1987
Clive e t al. Scheme I
clizations of the types shown in eq 2 and 3. R*+
@A
-
?
"
S
A
-
X
"
A
(1)
A
H
(3)
In regard to the radical cyclization, at least three areas of research can be discerned in recent publications: (i) development of methods to render members of the common compound types easily amenable to the tec "que of radical cyclization.6 (ii) study of the characteristics of the ring closure itself.' (iii) use of radical cyclization in the synthesis of complex molecule^.^ Naturally, the last of these areas depends on the status of the other two, and while considerable mechanistic information is available on radical cyclization,' there is an obvious need for the development of simple methods that allow the process to be applied to those classes of compounds such as olefins,8 ketone^,^^,^ acids,1° and allylic alcohols6 that are encountered most frequently in synthesis. In this context, we report full details of our workga on the Michael addition-radical cyclization sequence (Scheme I). In the first step a ketone is converted into its enamine, which is then allowed to react with a Michael acceptor 1 carrying groups X and Y that are chosen on the basis of criteria described below. The adduct 2 is treated with a lithium acetylide (2 3) to produce an acetylene in which the triple bond is suitably located to capture the radical (see 4) produced by treatment with a stannane (3 4). Ring closure (4 5 6)then affords material that can be cleaved (6 7) by ozonolysis to a cyclopentanone.
-
-- -
-
Results and Discussion The requirements of the Michael acceptor 1 are that it should react in the desired sense with enamines," it should contain a group X of such a nature that the bond C-X undergoes homolysis on treatment with a stannyl radical R,Sn', and it should contain a substituent Y that can be (5) Recent examples: (a) Stork, G.; Sofia, M. J. J . Am. Chem. SOC. 1986,108, 6826. (b) Hart, D. J.; Huang, H . 4 . Tetrahedron Lett. 1985, 26,3749. (c) Curran, D. P.; Rakiewicz, D. M. Tetrahedron 1985,41,3943. (d) Hanessian, S.; Beaulieu, P.; Dub& D. Tetrahedcron Lett. 1986, 27, 5071. (e) Wilcox, C. S.; Gaudino, J. J. J. Am. Chem. SOC.1986,108, 3102. (f) Clive, D. L. J.; Angoh, A. G.; Bennett, S. M. J. Org. Chem. 1987,52, 1339. (6) E.g.: (a) Mohammed, A. Y.; Clive, D. L. J. J . Chem. SOC., Chem. Commun. 1986, 588. (b) Stork, G.; Mook, R., Jr.; Biller, S. A,; Rychnovsky, S.D. J . Am. Chem. SOC.1983, 105, 3741. (7) Beckwith, A. L. J. Tetrahedron 1981, 37, 3073. (8) (a) Clive, D. L. J.; Beaulieu, P. L. J. Chem. SOC.,Chem. Commun. 1983, 307. (b) Clive, D. L. J.; Beaulieu, P. L.; Set, L. J. Org. Chem. 1984, 49,1313. (c) Angoh, A. G.; Clive, D. L. J. J. Chem. SOC.,Chem. Commun. 1985, 980. (9) (a) Angoh, A. G.; Clive, D. L. J. J . Chem. SOC.,Chem. Commun. 1985, 941. (b) Set, L.; Cheshire, D. R.; Clive, D. L. J. Zbid. 1985, 1205. (IO) Bennett, S. M.; Clive, D. L. J. J . Chem. SOC.,Chem. Commun. 1986, 878. (11)Cf.: (a) Madsen, J. 0.; Lawesson, S.-0. Bull. SOC.Chim. Belg. 1976, 85, 805. (b) Cook, A. G. Enamines: Synthesis, Structure and Reactions; Marcel Dekker: New York, 1969; p 16.
1
Ph,SnH
mz
7
6
used as a starting point for further manipulation. We have used the values X = Br and SePh,12and we examined the three Michael acceptors 8,139,14 and These are SsPh +S02Ph
8
SO2Ph
10
9
readily prepared in two steps, as follows: Reaction of benzeneselenenyl chloride with an excess16 of acrylonitrile and base-induced elimination of hydrogen chloride from the product gives 8. Compound 9 is similarly prepared from phenyl vinyl sulfone and benzeneselenenyl bromide. Likewise, compound 10 is available by the successive action of bromine and base on the sulfone. Each of these substances undergoes the classic1' Michael reaction with enamines to afford ketones after mild aqueous hydrolysis. The ketones we prepared were made from pyrrolidine enamines and are shown in Table I. As expected, each ketone was obtained as a mixture of diastereomers, four in the case of 20a18 and two in each of the other examples. Each Michael adduct was treated with lithium phenylacetylide, and some (see Table I) were also treated with the lithium salts of the acetylenes 25 and 26. In no case Me-H
EtO-H
25
26
were any problems experienced due to deprotonation a to the carbonyl or at the other acidic center. The acetylenic unit should be properly constituted to facilitate the ring closure (see Scheme I, 4 5), and, since disubstituted acetylenes undergo radical cyclization appreciably faster
-
(12) Clive, D. L. J.; Chittattu, G. J.;Farina, V.; Kiel, W. A,; Menchen, S.M.; Russell, C. G.; Singh, A.; Wong, C. K.; Curtis, N. J. J . Am. Chem.
Soc. 1980, 102, 4438. (13) Janousek, 2.; Piettre, S.; Gorissen-Hervens, F.; Viehe, H. G. J . Organomet. Chem. 1983,250, 197. (14) Piettre, S.; Janousek, 2.; Merenyi, R.; Viehe, H. G. Tetrahedron 1985, 41, 2527. (15) Carlier, P.; Gelas-Mialhe, Y.; Vessiere, R. Can. J . Chem. 1977,55, 3190. (16) It is essential to use a large (10-fold) excess of acrylonitrile in acetonitrile at 65 "C. (17) Stork, G.; Brizzolara, A.; Landesman, H.; Szmuszkovicz, J.; Terrell, R. J . Am. Chem. SOC. 1963,85, 207. Barieux, J.-J.; Gore, J. Bull. SOC. Chim. Fr. 1971, 1649. (18) For a discussion of the stereoselectivity of enamine reactions, see: Hickmott, P. W. Tetrahedron 1982,38,1975. Hickmott, P. W. Ibid. 1982, 38, 3363.
J. Org. Chem., Vol. 52, No. 22, 1987 4945
Five-Membered Ring Construction Table 1" K e w b (R Yield)
Cyellauon M u c l [Slow (SI or Far! 0AddiUon IYicld]
Cycbauon R e a r " (9.Y r l d )
K L M ~ (%Yield)
Cycbauon h w m r
1%Y d d )
Cyrbanuon Rodua ISlow (SI or Fan AddiUon 9. Yield]
m
a:: (.& SOtPh
Ilb 182 (= 16n)
(51j
H 1% (i 16~)
I8b
(5: 12)
191 (i 161)
iPh
+
19b
OH CHPh B
C
N
(5,911'
1%
13b
Ph
B Ph PI
CN I4b
OEl
1%
(96) E
SO,Ph
Except where indicated, yields refer to isolated products. *Ketones were prepared from the corresponding pyrrolidine enamines. Slight impurities. Two isomers (1:l.l). d68% from enamine. Two isomers (-1:l). e A t least three isomers. fTwo isomers (1:l). #Four isomers (-2.2:1.9:1.6:1). hAt least six isomers. 'Two isomers (-1:1.4). jTwo main isomers (-1:l.l); less than 7.5% of two other isomers. k A t least three isomers. 'Two isomers (-1:2). "Two isomers (1:l); trace of other isomers. " A t least six isomers. 'Two isomers (1:l) separated into two fractions: higher R, (21% yield) corresponding to one isomer; lower R, (50% yield) corresponding to a mixture of both isomers. "Four isomers (1:2.3:3.7:4.3). q Corrected for recovered starting material. Mainly one isomer; yield before correction for recovered starting material, 25%. #TWO isomers (1:l). tFour isomers (2.5:2.75:2.5:1). "One isomer. "One crystalline isomer obtained in 32% yield from 16b (24% from 16a). WThreeisomers (3.8:1.8:1) obtained in 67% yield by evaporation of mother liquors from crystallization of 16b (51% from 16a). "Three isomers; the two major components being in a ratio of 1:1.4. YObtained as two fractions: higher R, (13% yield) was a mixture of two isomers (1:l); lower R, (23% yield) was a mixture of two other isomers ( M . 6 ) . 'Four isomers (6.3:4.9:2.1:1). n°Four isomers (2.7:1.3:2:1). bbThreeisomers (3:2:1). ccTwo isomers (1:l). ddFour isomers (3:2:2.3:1). eeCombined yield of 21c and 21c'. Ratio of 21c to 21c' 2.3:l. ffFour isomers (4.8:3.9:4.7:1). gg See the text. kkThreemain isomers (4.3:2.5:1);trace of a fourth isomer. ' I Three isomers (2:1:1.3). Material that was largely one isomer was obtained by crystallization. j l Four isomers (1:1.6:2.2:4.2) identical with 19c.
than terminal acetylene^,'^ we did not examine the use of acetylene itself (for production of compounds of type 3, R = H). After radical cyclization, the carbon originally carrying the substituent R (see 3, Scheme I) has changed from sp to sp2hybridization. The nature of the substituent should allow cleavage of the double bond to a ketone20 and, preferably, should allow other reactions as well. To this (19)For example, the cyclization shown in (i) is 39 times as fast as that shown in (ii): Crandall, J. K.; Michaely, W. J. J. Org. Chem. 1984,49,
4244. H
i
ii
(20) R = SiR'3 is not ideal: Buchi, G.; Wuest, H. J.Am. Chem. SOC. 1978,100, 294.
end we examined acetylene 26, the specific aim being to develop an aldehyde synthesis along the lines of eq 4. OEt
til-.
u-
CHO
u -
H+
There exists close analogy in the literature21for the radical closure, but with the example we studied (compound 22b, see Table I), our attempts to carry out the cyclization were unpromising and gave complex mixtures. Table I lists the hydroxy acetylenes that we prepared as well as one example of a hydroxy nitrile (compound 23b) that was also anticipatedsb to be suitable for our purposes. (In the event, however, 23b did not undergo cyclization.22) (21) Ohnuki, T.; Yoshida, M.; Simamura, 0. Chem. Lett. 1972,797. (22) &Ex0 closure of a radical onto a nitrile triple bond is slower than onto a terminal acetylene: Griller, D.; Schmid,P.; Ingold, K. U. Can. J. Chem. 1979;57,831.
4946 J . Org. Chem., Vol. 52, No. 22, 1987
Clive et al.
T a b l e I1
(33
,iY,
CN
ILd
H
I -go%) one compound ('H NMR), which was identified as the cis ring-fused material 18c': mp 147-148 OC; 'H NMR (CDC13, 200 MHz) 6 0.74-2.17 (m, 10 H), 2.48 (m, 1 H), 3.30 (s, 1 H), 4.26 (m, 1 H), 6.81 (d, J = 1.5 Hz, 1 H), 7.32 (m, 5 H), 7.58 (m, 3 H), 7.94 (m, 2 H). The trans ring-fused compound 18c (44.3 mg, 12%) was also isolated from the flash chromatography: 'H NMR (CDC13,200 MHz) 6 0.67-2.06 (m, 11 H), 3.10 (d, J = 1.5 Hz, 1 H), 4.17 (dt, J = 1.5, 8.5 Hz, 1 H), 6.60 (dd, J = 1.5 Hz, 1 H), 7.26 (m, 5 H), 7.58 (m, 3 H), 7.94 (m, 2 H). Octahydro-1-ethylidene-7ahydroxy-2-(phenylsulfonyl)-la-indene (19c). The procedure employed for 15c was followed using triphenyltin hydride (336.7 mg, 0.96 mmol), AIBN (5 mg, 0.03 mmol), and selenides 19b (274.1 mg, 0.59 mmol) in dry benzene (30 mL). Flash chromatography of the residue over silica gel (2 X 15 cm) using 25% ethyl acetate-hexane gave two compounds as thick syrups, which were each a chromatographically (TLC) inseparable mixture of two different isomers ('H NMR) together with unreacted starting material (126.0 mg, 46%). The compound of higher R, (24.3 mg, 13% yield; 25% based on conversion) was composed of two isomers in a 1:1 ratio ('H NMR): 'H NMR (CDCl,, 200 MHz) 6 1.02-2.01 (m, 13 H), 2.08 (br d, J = 11.5 Hz, 0.48 H), 2.46 (br d, J = 11.5 Hz, 0.52 H), 2.96 (d, J = 1.5 Hz, 0.54 H), 3.37 (d, J = 1.5 Hz, 0.46 H), 3.99 (br t, J = 9.0 Hz, 0.45 H), 4.33 (br t, J = 8.0 Hz, 0.55 H), 5.62 (dq, J = 1.5,7.5 Hz, 0.51 H), 5.92 (dq, J = 1.5,7.0 Hz, 0.49 H), 7.48-7.75 (m, 3 H), 7.92 (m, 2 H). The compound of lower R , (41.2 mg, 23% yield; 42% based on conversion) was composed of two isomers in a L1.6 ratio ('H NMR): 'H NMR (CDCl,, 300 MHz) 6 0.59-2.56 (m, 14.5 H), 3.86 (s, 0.38 H), 3.99 (m, 0.60 H), 4.10 (m, 0.23 H), 4.40 (br t, J = 9.0 Hz, 0.32 H), 5.81 (dq, J = 1.5, 7.5 Hz, 0.62 H), 5.99 (dq, J = 1.5, 7.0 Hz, 0.38 H), 7.42-7.75 (m, 3 H), 7.94 (m, 2 H). Octahydro-7a-hydroxy-5-( 1,l-dimethylethyl)-1-(phenylmethylene)-2-(pheny1sulfonyl)-lH-indene(20c). The procedure employed for 15c was followed using selenides 20b (47.9 mg, 0.083 mmol) in benzene (40 mL), triphenyltin hydride (44.5 mg, 0.127 mmol) in benzene (5 mL), and AIBN (2 mg, 0.01 mmol) in benzene (5 mL). The mixture was stirred under reflux for 15 h and then worked up. Flash chromatography of the crude product over silica gel (1 X 15 cm) using 25% ethyl acetate-hexane gave 20c (22.9 mg, 65%) as an oily mixture of three isomers in a 5:4:1 ratio ('H NMR), which was resolvable into two spots by TLC (silica, 25% ethyl acetate-hexane). Total material: FT-IR (CHC1, cast) 3480,1440,1295,1285,1141,1078,749cm-': 'H NMR (CDCl,, 300 MHz) 6 0.42-2.06 (m, 18.5 H), 2.54 (m, 0.5 H), 3.12 (d,J=1.5Hz,0.33H),3.19(d,J=1.5Hz,0.17H),3.60(s,0.50 H), 4.12 (m, 0.10 H), 4.19 (dt, J = 1.5, 8.5 Hz, 0.50 H), 4.30 (dt, J = 1.5, 8.5 Hz, 0.40 H), 6.56 (d, J = 1.5 Hz, 0.17 H), 6.59 (d, J = 1.5 Hz, 0.33 H), 6.82 (d, J = 1.5 Hz, 0.50 H), 7.29 (m, 5 H), 7.60 (m, 3 H), 7.92 (m, 2 H); 13C NMR (CDC13,75.5 MHz) 6 (nonarometic signals only) 14.2, 21.4, 22.3, 23.4, 23.5, 25.7, 25.8, 27.3, 27.4, 27.5, 27.7, 28.9, 29.6, 30.0, 31.0, 32.0, 32.1, 32.4, 32.8, 34.3, 34.3, 40.9, 43.7, 46.3, 47.7, 49.4, 49.5, 69.0, 69.5, 69.8, 76.2, 78.0, 80.5; exact mass, m / z [(M - S0,C6H6)+] calcd for C20H2i0 283.2062, found 283.2063. (E)-(7aR*,2S*,3aR*)-Octahydro-7a-hydroxy-l-(phenylmethylene)-2-(phenylsulfonyl)-lH-indene (21c) and (7aR *,3aS*)-Octahydro-7a-hydroxy-1 -(phenylmethylene)2-(phenylsulfonyl)-lH-indene (21c') from Bromide 21b. The procedure employed for 15c was followed using bromides 21b (639.1 mg, 1.43 mmol) in benzene (60 mL), triphenyltin hydride (745.2 mg, 2.12 mmol) in benzene (10 mL), and AIBN (10 mg, 0.06 mmol) in benzene (10 mL). After evaporation of the solvent, the crude product mixture was taken up in either (ca. 25 mL) and was stirred with an aqueous solution (ca. 20 mL) containing an excess of potassium fluoride.34 The precipitated tri-n-butyltin fluoride was removed by filtration, and the ether layer was separated, dried (MgSOJ, and evaporated. Flash chromatography (34) Liebner, J. E.; Jacobus, J. J . Org. Chem. 1979, 44, 449
Clive et al. of the residue over silica gel (3 X 15 cm) using 25% ethyl acetate-hexane gave an oily mixture of two compounds 21c and 21c' (489 mg, 92%) in a 2.3:l ratio: 'H NMR (CDCl,, 300 MHz) 6 0.70-1.68 (m, 4 H), 1.80-2.04 (m, 6 H), 2.48 (m, 1 H), 3.10 (d, J = 1.5 Hz, 0.3 H), 3.30 (s, 0.7 H), 4.17 (dt, J = 1.5, 8.5 Hz, 0.3 H), 4.25 (t, J = 8.5 Hz, 0.7 H), 6.59 (d, J = 1.5 Hz, 0.3 H), 6.80 (d, J = 1.5 Hz, 0.7 H), 7.30 (m, 5 H), 7.59 (m, 3 H), 7.94 (m, 2 H). In another experiment, the two compounds obtained as above were separated. The minor compound, which was of higher R, was identified as trans ring-fused material 21c: 'H NMR (CDCl,, 400 MHz) 6 0.72-2.06 (m, 11 H), 3.10 (d, J = 1.5 Hz, 1 H), 4.16 (dt, J = 1.5, 9.0 Hz, 1 H), 6.62 (d, J = 1.5 Hz, 1 H), 7.32 (m, 5 H), 7.68 (m, 3 H), 7.96 (m, 2 H); 13C NMR (CDCl,, 50.3 MHz) 6 21.4, 25.2,25.5, 29.0, 33.0,34.6,49.0,68.8, 76.6, 127.8, 129.1, 129.2, 129.3, 129.5, 133.4, 133.9, 136.1, 136.3, 139.2. The major component, which was of lower Ri and was identified as cis ring-fused material 21c', was contaminated by some of the above isomer: 'H NMR (CDCl,, 200 MHz) 8 0.70-2.08 (m, 10 H), 2.48 (m, 1H), 3.10 (d, J = 1.5 Hz, 0.1 H), 3.30 (s, 0.9 H), 4.17 (m, 0.1 H), 4.25 (t, J = 8.5 Hz, 0.9 H), 6.59 (d, J = 1.5 Hz, 0.1 H), 6.79 (d, J = 1.5 Hz, 0.9 H), 7.31 (m, 5 H), 7.58 (m, 3 H), 7.92 (m, 2 H); 13C NMR (CDCl,, 50.3 MHz) 6 22.5, 23.9, 29.3, 29.5, 31.4, 48.3,69.6, 80.2, 127.8, 127.8, 129.1, 129.2, 129.4, 133.9,135.2, 135.7, 136.3, 137.5. Octahydro-l-ethylidene-7a-hydroxy-2-(phenylsulfonyl)-la-indene (24c)from Bromides 24b. The special procedure employed for 15c was followed using triphenyltin hydride (268.0 mg, 0.76 mmol), AIBN (10 mg, 0.06 mmol), and bromides 24b (193.4 mg, 0.50 mmol) in dry benzene (65 mL). Reflux was continued for 15 h, and then the product mixture was processed as for 21c and 21c'. Flash chromatography of the residue over silica gel (2 X 15 cm) using 25% ethyl acetate-hexane gave 24c (138.0 mg, 90%) as a thick syrup, which was a mixture of four isomers in a 1:1.6:2.2:4 ratio ('H NMR). The material was identical ('H NMR) with that generated from 19b: FT-IR (CHC13 cast) 3480, 1438, 1292, 1136 cm-'; 'H NMR (CDCl,, 300 MHz) 6 0.59-2.56 (m, 14.5 H), 2.96 (d, J = 1.5 Hz, 0.18 H), 3.37 (d, J = 1.5 Hz, 0.11 H), 3.86 (s, 0.24 H), 3.99 (m, 0.47 H), 4.10 (m, 0.18 H), 4.33 (br t, J = 8.0 Hz, 0.09 H), 4.40 (br t, J = 9.0 Hz, 0.20 H), 5.61 (dq, J = 1.5, 7.5 Hz, 0.19 H), 5.81 (dq, J = 1.5, 7.5 Hz, 0.36 H), 5.91 (dq, J = 1.5, 7.0 Hz, 0.19 H), 5.99 (dq, J = 1.5, 7.0 Hz, 0.25 H), 7.42-7.76 (m, 3 H), 7.92 (m, 2 H); 13C NMR (CDCI,, 75.5 MHz) 6 13.7, 14.0, 15.7, 21.2, 21.5, 22.2, 22.3, 23.4, 24.8, 25.0, 25.1, 25.4, 25.8, 26.5, 28.9, 29.2, 30.1, 30.5, 30.6, 32.2, 33.2, 34.4, 36.1, 46.4, 46.8, 47.3, 48.3, 58.8, 64.6, 65.0, 67.7, 67.8, 79.6, 126.9, 128.9, 129.0, 129.1, 129.3, 130.4, 133.7, 133.8, 137.0; exact mass m / z calcd for C17H2203S306.1290, found 306.1283. Octahydro-7a-hydroxy-1-oxo-1 H-indene-2-carbonitrile (12d). An ozone-oxygen stream was bubbled through a solution of ketones 12c (120 mg, 0.474 mmol) in dry methanol (5 mL) at -78 OC until the starting had just disappeared (5 min; TLC, silica, 25% ethyl acetate-hexane). Argon was passed through the solution for 5 min to remove the excess of ozone, and trimethyl phosphite (0.08 mL, 6.60 mmol) was injected. The cold bath was removed, and the solution was stirred for 12 h. Evaporation of the solvent and flash chromatography of the crude product over silica gel (1 X 15 cm) with 25% ethyl acetate-hexane gave 12d (67 mg, 79%) as a mixture of isomers that was homogeneous by TLC (silica, 24% ethyl acetate-hexane): IR (neat) 3440, 2245, 1750 cm-'; 'H NMR (CDCl,, 200 MHz) 6 1.00-2.65 (m, 11 H), 3.10-3.95 (m, 2 H); 13C NMR (CDCl,, 100.6 MHz) 6 20.2, 24.1, 24.4, 25.2, 25.3, 29.8, 30.0, 30.4, 34.7, 35.5, 43.8, 75.0, 75.2, 116.9, 117.5,203.5, 203.9; exact mass, m / z calcd for C10H13N02179.0942, found 179.0944. Anal. Calcd for CI0Hl3NO2:C, 67.00; H, 7.31; N, 7.81. Found: C, 67.67; H, 7.29; N, 7.46. (7aR *,3aR *)-Octahydro-7a-hydroxy-l-oxo-2-(phenylsulfonyl)-la-indene(17d). A gentle stream of ozone was passed through a cold (-78 OC) solution of alkene 17c (56.5 mg, 0.153 mmol) in 41 dichloromethane-methanol (5 mL) until a blue color developed (ca. 3 min). The excess of ozone was removed by a stream of argon, and dimethyl sulfide (0.5 mL) was added dropwise. The mixture was allowed to warm to room temperature over ca. 15 min and stirred for 15 h. Evaporation of the solvent and flash chromatography of the residue over silica gel (1X 15 cm) using 25% ethyl acetate-hexane gave a white solid 17d (32.0 mg, 71%) as a chromatographically (TLC) inseparable mixture
J. Org. Chem. 1987, 52, 4953-4961 of two isomers in a k1.1 ratio ('H NMR). The material was recrystallized from ether-dichloromethane: mp 141-142 "C; FT-IR (Nujol) 3509,3487,1744,1447,1377,1318,1302,1292,1180, 1146,1084,1073,738,727,585,565cm-'; 'H NMR (CDCl,, 300 MHz) 6 1.10-1.96 (m, 9.5 H), 2.30 (m, 2.0 H), 2.62 (qd, J = 1.5, 6.5, 13.5 Hz, 0.5 H), 3.84 (dd, J = 8.5, 9.5 Hz, 0.51 H), 4.12 (dd, J = 1.5, 9.7 Hz, 0.46 H), 7.59 (m, 2 H), 7.69 (m, 1 H), 7.90 (m, 2 H); 13C NMR (CDCl,, 50.3 MHz) 6 20.3, 24.2, 24.3, 25.2, 25.4, 26.8, 27.0, 30.3, 30.4, 42.6, 43.6, 66.9, 68.8, 75.7, 76.5, 129.0, 129.1, 129.2, 134.0, 134.1, 134.2, 137.8, 138.6, 202.3, 203.5; exact mass, m / z [(M - CO)'] calcd for C14H1803S266.0977, found 266.0975. Anal. Calcd for C15H1804S:C, 61.20; H, 6.16. Found: C, 61.08; H, 6.15. (7aR *,3aR *)-Octahydro-7a-hydroxy-l-oxo-2-(phenylsulfonyl)-1-H-indene (16d) a n d (7aR*,3aS*)-Octahydro7a-hydroxy-l-oxo-2-(phenylsulfonyl)-l-H-indene (16d'). The procedure for 17d was followed using alkenes 16c and 16c' (237.0 mg, 643.2 "01) in 5 1 dichloromethane-methanol(25 mL). Flash chromatography of the crude product over silica gel (2 X 15 cm) using 25% ethyl acetate-hexane afforded two solids, which were each a chromatography (TLC) inseparable mixture of two isomers ('H NMR), together with cis ring-fused unreacted starting material (49.9 mg, 21%). The material of higher Rf 51.1 mg, 27% yield; 34% based on conversion) was recrystallized from ether-dichloromethane and identified as the trans ring-fused ketones 16d in a 1:l.l ratio that had not been altered ('H NMR) by crystallization: mp 140-145 "C; FT-IR (MeOH) 1752,1307,1147,1084 cm-'; 'H NMR (CDCI,, 300 MHz) b 1.09-1.95 (m, 9.5 H), 2.30 (m, 2 H), 2.62 (qd, J = 1.5,6.5, 13.5 Hz, 0.5 H), 3.82 (dd, J = 8.5, 9.5 Hz, 0.55 H), 4.12 (dd, J = 1.5,9.7 Hz, 0.45 H), 7.59 (m, 2 H), 7.69 (m, 1H), 7.90 (m, 2 H); 13C NMR (CDCI,, 75.5 MHz) 6 20.4, 20.4, 24.3, 24.4, 25.3, 25.4, 26.8, 27.1, 30.3, 30.4, 42.7, 43.6, 67.0, 68.9, 75.8,129.1,129.1, 129.1,129.2,134.1, 134.3; exact mass, m / z [(M
4953
- CO)+] calcd for C14H1803S266.0976, found 266.0975.
The compound of lower Rf (75.6 mg, 40% yield; 50% based on conversion) was identified as the cis ring-fused materials 16d': mp 120-150 "C; 'H NMR (CDC13,300 MHz) 6 1.162.46 (m, 11.65 H), 2.74 (m, 0.35 H), 3.99 (m, 1 H), 7.60 (m, 2 H), 7.70 (m, 1 H), 7.90 (m, 2 H); exact mass, m/z [(M - CO)' calcd for Cl4HI8O3S 266.0976, found 266.0975. Octahydro-7a-hydroxy-1-oxo-1-H-indene (16e). The general literature procedurez6was followed. Three strips of aluminum foil (1 X 5 cm) were dipped into a 2% w/v aqueous solution of mercurous chloride for 15 s, then into 95% ethanol, and finally into ether. The strips were immediately cut into 0.5-cm square pieces and dropped into a stirred solution of sulfones 16d and 16d' (30.8 mg, 0.105 mmol) in 10% aqueous THF (10 mL). Stirring was continued for 6 h, and the mixture was then refluxed for 3 h, cooled, filtered, and evaporated. The resulting oil was dissolved in dichloromethane,and the solution was dried (MgS04) and evaporated. Flash chromatography of the residue over silica gel (1 X 15 cm) using 25% ethyl acetate-hexane afforded unreacted starting material (8.0 mg, 25%) and 16e (12.0 mg, 74%; 98% based on conversion). Compound 16e: FT-IR (CC4cast) 3420, 1742, 1710, 1442 cm-l; lH NMR (CDCl,, 300 MHz) 6 0.78-2.58 (series of multiplets); 13C NMR (CDCI,, 300 MHz) 6 20.7, 24.2, 24.7, 24.9, 25.1, 25.8, 28.1, 30.5, 31.4, 34.2, 35.1, 42.2, 45.9,49.7,75.1,216.6; exact mass, m/z calcd for CgH& 154.0994, found 154.1000. Supplementary material available: Crystal structure data (23 pages) for 17c available from the authors.
Acknowledgment of financial support is m a d e t o t h e Natural Sciences and Engineering Research Council of Canada. We thank Dr. R. Ball of this department for the X-ray structure determination.
Structural and Solvent/Electrolyte Effects on the Selectivity and Efficiency of the Anodic Oxidation of Para-Substituted Aromatic Ethers. An Efficient Route to Quinol Ether Ketals and Quinol Ethers Michael P. Capparelli, Richard E. DeSchepper, and J o h n S. Swenton* Department of Chemistry, The Ohio State University, Columbus, Ohio 43210 Received July 8, 1987 The anodic oxidations of the methyl ethers of p-arylphenols [p-aryl = C6H5, o-CH3C6H4,p-CH30C6H4, 2-hydroxyethyl ethers of p-arylphenols [p-aryl = C6H5,o-CH3C6H4,p-CH30C6H4,3,4-(CH30)zC&13,2-thiopheneyl], and the 2-hydroxyethyl ethers of p-alkylphenols [p-R = CH3, CzH5, i-C3H7,t-C4Hg]and 4-methyl-1-naphthol were studied. The p-aryl aromatic ethers underwent anodic oxidation in good yield to give the corresponding p-quinol ether ketals. The ratio of nuclear to side-chain products from anodic oxidation of p-alkylanisolederivatives is dependent upon the electrolysis conditions. The 2-hydroxyethyl ether derivatives of p-alkylphenols markedly favor the formation of nuclear oxidation products-providing a useful route to the corresponding p-quinol ether ketals. In addition, methanolic potassium fluoride improves the efficiency of these anodic oxidation processes by about 400% relative to methanolic potassium hydroxide. These reactions were performed at a constant current (1.0-2.0 A) in a single cell and serve as preparative routes to p-quinol ether ketals and quinol ethers via acid hydrolysis. 0-[ (CH3)2-t-BuSiOCHz]C6H4, 0 - [ (H3CO)2HC]C6H4, o-HOzCC6H4],the
Introduction T h e anodic oxidation of aromatic compounds in methanol often serves as a general route for t h e preparation of quinone bisketals.1,2 Although 1,4-dimethoxy aromatic compounds are most often used for the oxidation, benz(1) Swenton, J. S. Acc. Chem. Res. 1983,16,74and references cited therein. (2) (a) Weinberg, N. L.; Belleau, B. J. Am. Chem. SOC.1963,85, 2525. (b) Henton, D. R.; McCreery, R. L.; Swenton, J. S. J. Org. Chem. 1980, 45,369. (c) Henton, D. R.; Anderson, D. K.; Manning, M. J.; Swenton, J. S. J. Org. Chem. 1980, 45, 3422.
0022-326318711952-4953$01.50/0
Scheme I. Side-Chain Oxidation of Para-Substituted Toluenes
2)H30t
(70- 87%)
X = O A c , CH3, But, Pr',
C I , OCH3
ene,3 monomethoxylated aromatic compound^,^,^ and heterocyclic ring systems5 have also been successfully em@ 1987 American Chemical Society
