Optically pure (S)-cyclopent-2-en-1-01and (S)-3-methoxycyclopentene AMALWAHHAB, DONALD F. TAVARES, AND ARVIRAUK'

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Department of Chemistry, The University of Calgary, Calgary, Alta., Canada T2N IN4 Received February 20, 1990 AMALWAHHAB, DONALD F. TAVARES, and ARVIRAUK.Can. J. Chem. 68, 1559 (1990). Optically pure (S)-cyclopent-2-en-1-01,[a];' -137.9" ( c 1.1, CHC13), and (S)-3-methoxycyclopentene, [ a ] i O-116.9" ( c 3.86, n-hexane), were prepared from ethyl (lR,2S)-2-hydroxycyclopentanecarboxylate,whlch is readlly available by yeast reduction of ethyl 2-oxocyclopentanecarboxylate. The optlcal purity of the alcohol was determined from its Mosher ester, and that of the ether by gas chromatography using a Ni-4-Pin column. Key words: (S)-cyclopent-2-en-1-01,(S)-3-methoxycyclopentene.

I i I

I

1

1

AMALWAHHAB, DONALD F. TAVARES et ARVIRAUK Can. J . Chem. 68, 1559 (1990). On a prCparC du (S)-cyclopent-2-en-1-01,[a]EO-137,9" (c 1,1, CHC13), et du (S)-3-mtthoxycyclopent&ne,[ a ] : - 116,Q0 (c 3,86, n-hexane), optiquement purs h partir du (lR,2S)-2-hydroxycyclopentanecarboxylated'Cthyle qui est facilement accessible par le bials d'une reduction du 2-oxocyclopentanecarboxylate d'6thyle h l'aide de levilres. On a dttermink la puretC optique de l'alcool en se basant sur la chromatographie gazeuse (utilisant une colonne de Ni-4-Pin) de son ester de Mosher ainsi que de son Cther. Mots clks : (S)-cyclopent-2-en-1-01,(S)-3-m6thoxycyclopent~ne. [Traduit par la revue]

Introduction Our interest in the chiroptical and the spectroscopic characteristics of cyclic allylic alcohols and ethers created a need for chemically and enantiomerically pure 2-cyclopenten-l-ol l and 3-methoxycyclopentene 2. Previously reported synthetic procedures for the preparation of the alcohol 1 fail in this respect. There are no reports of the preparation of the optically active ether 2 and it is not clear that the allylic alcohol could be converted to the ether without some racemization. Hill and Edwards (I) converted racemic 1 to the acid succinate, and partially resolved it with (+)-a-(1-naphthy1)-ethylamine. After eight recrystallizations and regeneration of the succinate, followed by LiA1H4 reduction, the specific rotation of 1 was [a];' +22.g0 (c 5, CC14), corresponding to about 15% ee. Denney et al. (2) achieved partial asymmetric induction in the reaction of cyclopentadiene with tert-butylhydroperoxide and the cupric salt of (+)-a-ethyl camphorate, and obtained a-ethyl-P-A2-cyclopentenylcamphorate, which upon LiA1H4 reduction yielded 1, [a]z6 - 13.6" (c 8.9, CHCl,). Asami and Kirihara (3) reported that the asymmetric transformation of cyclopentene oxide with lithium (S) -2- [(pyrrolidin - 1-yl)methy]]pyrrolidide gave 1 in 49% yield and 3 1% ee, [ a ];'- 55" (c 1.35, CC14). In the work of Sharpless and co-workers (4) introducing kinetic resolution of allylic alcohols by enantioselective epoxidatick, the reaction of racemic 1 was not reported. It failed to give satisfactory results in our hands.2 Sato et al. (5) obtained 1 in 77% yield and 82% ee, [a]E3 - 105.8" (c 1.14, CHC13), by asymmetric reduction of 2-cyclopenten-lone 3 with chiral aluminium hydride reagents. More recently, Kitamura et al. (6) reported that the BINAP-ruthenium(I1)catalyzed hydrogenation of 3 gave 1 in 50% yield and 79% ee. Although the optically active ether 2 has not been reported, a few reports have appeared for racemic 2. Alder and Flock (7a) prepared 2 by the reaction of 3-chlorocyclopentene with methanol, while Fleming and Thomas (7b) and Ishiyama et al. (7c) obtained 2 by methylation of 1. Inspired by the highenantioselectivity and the good yields of yeast reductions of ketones (8), we chose ethyl (1R,2S)-2'Author to whom correspondence may be addressed.

'A. Rauk and D. F. Tavares, unpublished results.

hydroxycyclopentanecarboxylate 5, which is easily obtainable by yeast reduction of ethyl 2-oxocyclopentanecarboxylate4, as our starting point. Scheme 1 depicts our strategy to prepare the chemically and optically pure compounds 1 and 2.

Results and discussion The baker's yeast reduction of ethyl 2-oxocyclopentanecarboxylate 4 by a slight modification of the procedure of Tsuboi et al. (9) gave chemically and enantiomerically pure ethyl (1R,2S)-2-hydroxycyclopentanecarboxylate5 in 80.3% yield. The more laborious procedure of Deol et al. (10) for the reduction of 4, which involved the preparation of freshly cultivated batches of a sterile mutant of Saccharomyces cerevisiae, baker's yeast, under strictly controlled conditions, failed to give satisfactory reduction in our hands. The absolute configuration of 5 was assumed (and subsequently verified) to be the same as that of the product of Deol et al. Hence, the absolute configuration of the alcohol belongs to the S ~ e r i e s . ~ This configuration is maintained all through the reaction sequence and will yield the (S)-2-cyclopenten-1-01 1. The specific rotation of 5, [a];' + 15. lo, was slightly higher than that of the product obtained by Deol et al., [a];' + 14.1". 'H and 13CNMR analysis of the Mosher ester of 5 showed it to consist of one isomer only. Hydrolysis of the hydroxy ester 5 with 25% NaOH, similar to the reported hydrolysis of ethyl (1R,2S)-hydroxycyclohexanecarboxylate (lo), gave ( 1R, 2s)-2-hydroxycyclopentanecarboxylic acid 6 in 74.2% yield, [a];' +28.0°. 'H and 13CNMR and the specific rotation of 6 indicated that racemization under the hydrolysis conditions did not occur. Attempts to selectively protect the alcohol of 5 as the silyl ether in the presence of the acid functionality gave a mixture of protected alcohol and protected acid; therefore, excess tert-butyldimethylchlorosilane and increased reaction times were required to fully protect both functionalities. The tert -butyldimethylsilyl ( 1R , 2s)-2-tert3 ~ n z y m egenerally s transform ketones into products possessing the S-configuration (where steric bulk determines the relative priorities) at the newly formed secondary alcohol unit. See K. Kieslich. Microbial transformations of chemical compounds excluding steroids and noncyclic structures. G. Thieme, Stuttgart. 1976.

bcolEt yeast reduction

QH 0,,,,,C02Et

9CH3

(1) Me1 * a 2 0 reflux (2) a. KOH:EtOH:H20/l:3:16; b. H' (3) oxalyl chloride

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(1) a. 25%NaOH; b. H+ (2) ~ - B U ( MSiCl, ~ ) ~imidazole, DMF

!

(1) oxalyl chloride (2) selenohydroxamic acid DMAP, Py, benzene (3) a. 0 3 , CH2C12,-780C; b. 1-pentane; c. reflux CC14

butyldimethylsiloxycyclopentanecarboxylate 7 obtained in 80% yield, [ a ] +24.6", was reacted with oxalyl chloride following the procedure of Wissner and Grudzinskas (11) to give (1R , 2s)-tert- butyldimethylsiloxycyclopentanecarbonyl chloride 8 quantitatively. The decarboxylative selenination of 8 according to the procedure of Barton et al. (12) gave l-tertbutyldimethylsiloxy-2-(2'-pyridylseleno)cyclopentane9 in 85.8% yield as a 7: 1 mixture of two diastereomers. The epimerization at carbon 2 of 9 was expected, since the decarboxylative selenination proceeds via a radical mechanism (12). The major isomer is inferred to be the trans from the chemical shift of the alkoxy carbon, CH-0-, in the 13CNMR spectrum, which appeared at 79.7 ppm compared to the minor at 75.8 ppm (13). The diastereomers of 9 were not separated, and were ozonized to give 1-tert-butyldimethylsiloxycyclopent-2-en10 in 77.2% yield. Deprotection of 10 gave (S)-2-cyclopenten-1-011 in 46% isolated yield after chromatography and vacuum distillation. The specific rotation of 1, [a];' -137.9", and the 'H and

'

wcocl selenohydroxarnic acid, DMAP, Py, benzene reflux

a. 0 3 , CH2C12,-78OC; b. 1-pentene; c. reflux pentane

13CNMR spectra of the MPTA ester of 1and that of the racemic alcohol indicated that 1 was indeed enantiomerically pure. It is worth noting that attempts to prepare optically active 2-phenylselenocyclopentanol by yeast reduction of 2-phenylselenocyclopentanone were not fruitful. The seleno moiety was unstable to the reduction conditions and was recovered as diphenyldiselenide. The a-seleno ketone without the yeast was stable in different buffered solutions, which leads us to think that the fermenting yeast is somehow interacting with the seleno moiety.4 To our knowledge, this is the first report of such an observation, since a-dithianyl ketones and P-thianyl ketones have been reduced with yeast without reported troubles (8, 14). The allylic ether 2 was synthesized by a parallel route starting from 5. The reaction of 5 with a large excess of silver(1) oxide and methyl iodide gave ethyl (1R,2S)-2-methoxycyclopentanecarboxylate 11 in 86.4% yield, [a];' +20.0°. Of several methods attempted for the hydrolysis of 11, the most satisfactory were Ba(OH)2:ethanol:H20( 1:4:25), and KOH:ethanol:H20 (1:3:16) with the former giving a 3.4:l and the latter a 3:l mixture of two diastereomers of (2s)-2-methoxycyclopentanecarboxylic acid 12. The chemical shift, in the 13C NMR spectrum, of the alkoxy carbon, C2, of the major isomer appeared at 83.8 ppm, and that of the minor at 85.4 ppm, indicating that the major isomer is most likely the cis diastereo4 ~ Kaija, . H. Kai, E. Kari, and K. Matti. Chem. Abstr. 100, 153628~(1984), reported that Se is incorporated into analogs of S-containing amino acids if yeast is grown in the presence of a source of inorganic Se.

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WAHHAB ET AL.

merS (13). The two diastereomers of 12 with oxalyl chloride in refluxing hexanes gave (2s)-2-methoxycyclopentanecarbonyl chloride 13 in 93% yield. Decarboxylative selenination of 13 gave ( 1S)- 1-methoxy -2-(2-pyridylse1eno)cyclopentane 14 in half the yield obtained from the same reaction with 8. The ozonolysis of 14 and thermal decomposition of the selenoxide by pouring over refluxing pentane produced (S)-3-methoxycyclopentene 2 in 68% isolated yield, [a]:0 -116.9". To our knowledge, this is the first report of the synthesis of optically active 2. The optical purity of 2 was determined by GC using a chiral column, Ni-4-Pin, and found to be 98.3%, i.e., approximately 97% ee. A sample of 2 prepared by methylation of optically active 1 by silver(1) oxide/methyl iodide was found to be >99% optically pure by chiral GC analysis as described above. This result verifies that the methylation of 1 under these conditions proceeds without epimerization, and also confirms the optical purity of the allylic alcohol 1.

Experimental General information Infrared spectra (IR) of liquids were recorded using KBr cells on a Nicolet 5-DX FT-IR prism grating spectrophotometer. Gas-liquid chromatography (GC) was accomplished with a Varian model 3700 gas chromatograph fitted with a DB-5, 30 m X 0.249 mm, fused silica column, 0.25 pm film thickness. Proton ('H) and carbon (I3C) nuclear magnetic resonance (NMR) spectra were recorded on a 200 MHz Bruker AC-200 spectrometer and signal positions are given in ppm (6). Flash column chromatography was done on 230-400 mesh silica gel. Rotations were measured on a Rudolph Autopol 111 automatic polarimeter. Ozone for ozonolysis was generated from a Welsbach ozonator model T-23. Solvents were purified and dried using standard methods. Baker's yeast, Saccharomyces cerevisiae type 11, was purchased from Sigma. The chiral column was an OV-1 (25 m x 0.25 inm fused silica) coated with 0.25 pm Ni-4-Pin. Yeast reduction of ethyl 2-oxocyclopentanecarboxylate A suspension of baker's yeast (12.0 g), sugar (152 g), MgSO, (1.0 g), KH2P04 (2.0 g), NH4H2P04(2.0 g), and CaC03 (5.0 g) in deionized H20 (1 L) was placed in a water bath at 35°C and allowed to ferment for 45 min (shaken occasionally). Ethyl 2-oxocyclopentanecarboxylate (10.2 g) was added dropwise and the last amount was transferred with the minimum volume of ethanol (1.5 mL). The mixture was magnetically stirred at room temperature for 18 h. A sample analysed by GC showed the disappearance of the starting material. The mixture was transfemed to a separatory funnel and extracted with ether (5 X 250 mL). The combined ether extracts were washed with saturated NaCl solution and dried over anhydrous MgS04 and filtered. Evaporation of the solvent and fractional distillation of the residue under reduced pressure gave (1R,2S)-2-hydroxycyclopentanecarboxylate 5 in 80.3% yield, bp 59-61°C/0.4 Torr (1 Tom = 133.3 Pa), >98% pure;6 [a];' +15.1° (c 1.57, CHC13) (lit. (10) [a]:' 14. lo (c 1.7, CHC13)). 'H NMR agreed well with reported data (10). 13CNMR, 6: 174.6 (C=O), 73.6 (CH-0), 60.4 (CH2-0), 49.5, 33.9, 26.1, 21.9, 14.0. The Mosher ester of 5 (MTPA ester) was prepared using (R)-amethoxy-a-trifluoromethylphenylacetic acid according to literature procedures (15). 'H NMR (CDC13), 6: 7.55-7.35 (m, 5H, aromatic), 5.69-5.63 (m, lH, CH-0), 4.2-3.89 (m, ABX3, 2H, 0-CH2),

+

'J. Pascual and J. Vinas. Chem. Abstr. 55,4383e (19611, reported that the saponificationof methyl cis-2-methoxycyclopentanecarboxylate with Ba(OH)2 gave 87% cis-2-methoxycyclopentanecarboxylic acid. 6 ~ ADDED o IN ~PROOF: ~ Noyori et al. (J. Am. Chem. Soc. 111, 9134 (1989)) reported that the hydrogenation of the methyl esters of 4 by (R)-BINAP-Ru complex gave a 99:l mixture of the trans hydroxy ester (92% ee) and its C2 epimer (93% ee).

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3.495 (d, J = 1.1 Hz, 3H, 0-CH3), 3.0-2.89 (8 lines, lH, CH-C02), 1.2 (t, J = 7.6 Hz, 3H, CH2-CH3). I3CNMR (CDCI~), 6: 170.9 (C=O), 166.0 (C=O), 129.5, 128.3, 127.5, 126.1, 120.0, 79.8 (CH-0), 60.7 (0-CH3), 55.2,49.1, 32.3, 25.1, 21.6, 13.9. Hydrolysis of hydroxy ester 5 The hydroxy ester 5 (17.14 g, 0.103 mol) was stirred with 25% NaOH aqueous solution (85.7 mL) at room temperature according to the procedure in ref. 10. The hydroxy acid 6 was obtained in 74.2% yield, [a]:' +28.0° (c 1.866, CHC13), as an oil that solidified on standing. IR (thin film): 3676-2291, 1711 cm-I. 'H NMR, 6: 6.8 (br, 2H, -OH and -C02H, exchange with D20), 4.50 (dd, lH, J = 2.4, 4.6 HZ, CH-O), 2.77 (dt, lH, J = 4.6, 9.2 HZ, CH-C02), 2.11-1.61 (m, 6H, ring CH2's). I3cNMR, 6: 178.7 (C02H), 73.9 (CH-OH), 49.6 (CH-C02H), 33.9, 25.9, 2 1.9. Silylation of hydroxy acid 6 Following the procedure of Wissner and Grudzinskas (11), the hydroxy acid 6 (18.0 g, 0.135 mol), tert-butyldimethylchlorosilane (50.0 g, 0.332 mol), and imidazole (45.17 g, 0.663 mol) in DMF (80 mL) were stirred at room temperature. After 44 h, 50% of 6 had reacted. tert-Butyldimethylchlorosilane (25.0 g) and imidazole (22.5 g) were added and the reaction mixture was stirred a further26 h. The reaction mixture was diluted with ether and washed three times with H20, then once with saturated NaCl solution. The solvent was removed by fractional distillation and the residue was distilled under reduced pressure to give the disilyl derivative of 7 in 80% yield, bp 120-124"C/0.7 Torr, as a colorless oil; [a]:' +24.6" (c 1.698, CHCI,). 'H NMR, 6: 4.35 (m, lH, CH-0-Si), 2.7 (m, lH, CH-C02), 2.2-1.5 (multiplets, 6H, ring CH2's), 0.94 (s, 9H, t-Bu-Si), 0.92 (s, 9H, t-Bu-Si), 0.27, 0.25; 0.04, 0.03 (singlets, 3H each, CH3-Si). 13CNMR, 6: 172.9 (C02-Si), 75.6 (CH-0-Si), 53.O(CH-C02Si), 34.9,25.8,25.6,25.2,21.6, 18.0, 17.6, -4.57, -4.61, -4.69, -4.84. Anal. calcd. for C18H3803Si2:C 60.28, H 10.68; found: C 60.09, H 10.56. Reaction of disilyl 7 with oxalyl chloride Oxalyl chloride (2.3 mL, 26.2 mmol) was added dropwise to a mixture of disilyl7 (7.56 g, 21.1 mmol) and 3 drops of DMF in CH2C12 (21 mL) cooled in an ice bath according to the procedure of Wissner and Grudzinskas (11). After work-up and evaporation of the solvent, the residue was connected to a vacuum pump and the by-product, tert-butyldimethylchlorosilane, was trapped. The acid chloride 8 (5.6 g, 100% yield) was used in the next step without distillation. IR (thin film): 1811 cm-'. 'H NMR (CDC13), 6: 4.70 (m, lH, HC-0-Si), 3.24 (m, lH, HC-COCl), 2.35-1.57 (m, 6H, ring CH2's), 0.86 (s, 9H, t-Bu-Si), 0.11 (s, 3H, CH3-Si), 0.08 (s, 3H, Si-CH3). 13CNMR (CDC13),6: 172.2 (C=O), 75.8 (HC-0-Si), 63.7 (HC-COCl), 34.9, 25.6, 25.1, 22.2, 17.9, -4.4 (CH3-Si), -5.2 (Si-CH3). Reaction of acid chloride 8 with selenohydroxamic acid The acid chloride 8 (5.5 g, 20.9 mmol) in benzene (110 mL) was added dropwise over 30 rnin to a refluxing solution of selenohydroxamic acid (4.84 g, 27.6 mmol), pyridine (5.5 mL), and DMAP (0.264 g) in benzene (220 mL) under argon according to the procedure of Barton et al. (12). The crude product upon chromatography over silica (eluting with 3% EtOAc: pet. ether) gave the selenide 9 in 85.8% yield as a 7:l mixture of two diastereomers. [a];' - 15.0" (c 1.093, CHC13). 'H NMR (CDC13),6: major8.41 (m, lH), 7.38 (m, 2H), 6.99 (m, lH), 4.30 (m, lH, HC-0), 3.9 (m, < lH, HC-Se), 2.5-1.5 (multiplets, 6H, ring CH2's), 0.85 (s, 9H, t-Bu-Si), 0.029 (s, 3H, CH3-Si), 0.019 (s, 3H, Si-CH3). I3cNMR (CDC13), 6: major 156.5, 149.9, 135.7, 125.7, 120.1 (pyridylcarbons), 79.7 (HC-OSi), 48.6, 33.8, 30.6, 25.7 (t-Bu-Si), 22.4, 17.9, -4.7 (CH3-Si), -4.8 (Si-CH3); minor 75.8 (CH-0). Anal. calcd. for Cl6H2,N0SeSi: C 53.92, H 7.64, N 3.93; found: C 54.26, H 7.78, N 3.74. Ozonolysis of selenide 9 The selenide 9 (6.4 g) in CH2C12was cooled in a Dry Ice - acetone bath and ozone (2.5% 0 3 ) was bubbled through the solution until the

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CAN. J. CHEM. VOL.

blue color persisted. Oxygen was passed through the solution to drive off excess ozone and, very cautiously, 1-pentene(37 mL) was added to the cold mixture, and the reaction mixture was added over refluxing CC14 (177 mL) at a rate to maintain reflux. After completion of addition, the mixture was refluxed for a further 30 min, then the solvents were removed under reduced pressure. The allylic silyl ether 10 was obtained by vacuum distillation of the residue in 77.2% yield, 35"C/0.5 Torr); [a]? -84.9" (c 0.855, CHC1,). 'H NMR (CDCl,), 6: 5.92 (m, lH, HC=), 5.7 (m, lH, =CH), 4.94 (m, lH, HC-0), 2.6-2.21 (m, 3H), 1.67 (m, lH), 0.84 (s, 9H, t-Bu-Si), 0.02 13C NMR (CDCl,), 6: 133.9 (HC=), (s, 6H, CH3-Si-CH,). 133.4 (=CH), 78.1 (HC-O), 33.5,31 .O, 26.0 (t-Bu-Si), 18.3, -4.6 (CH3-Si-CH3). Exact Mass calcd. for CllH220Si: 198.3822; found: 198.3828.

68, 1990

stirring at room temperature overnight, gave a 3.4:l mixture of diastereomers, with the major being the same as above. 'H NMR (CDCl,), 6: 11.48 (br s, lH, C02H), 4.03 (m, lH, CH-0), 3.339 and 3.334 (two singlets), 2.87 (m, lH, CH-C02), 2.2-1.55 (m, 6H, ring CH2's). ',c NMR (CDCl,), 6: major 177.9 (C=O), 83.8 49.3, 30.3, 25.6, 21.8; minor 181.0 (CH-0), 60.0 (0-CH,), (C=O), 85.4 (CH-0), 56.9 (0-CH,), 50.3, 32.1, 28.5, 23.4. Methoq acid chloride I3 A mixture of methoxy acid 12 (3.34 g, 23.2 mmol) and oxalyl chloride (2.7 mL) in hexane (20 mL) was refluxed overnight. Evaporation of the solvent and excess oxalyl chloride gave acid chloride 13 in 93% yield, pure enough to use in the next step. IR (thin film): 1797, 1791 cm-'. 'H NMR (cDc~,), 6: 4.12 (m, lH, CH-0), 3.34(s, 3H, 0-CH3), 3.28-3.17 (8 lines, lH, CH-COCl), 2.25-1.62 (m, 6H, ring CH2's). 13C NMR (CDCl,), 6: 175.6 (C=O), 84.8 (CH-0), 62.2 (0-CH,), 57.1, 32.0, 29.1, 23.2.

(S)-2-Cyclopenten-1-01I Tetrabutylamrnonium fluoride (47.9 mL, 1.0 M solution in THF) was added via a syringe to the silyl ether 10 (9.5 g, 47.9 mmol) under Decarboqlative selenination of acid chloride I3 argon. After stirring the reaction mixture at room temperature for The acid chloride 13 (2.29 g, 14.1 mmol) in benzene (70 mL) 90 min, the mixture was transferred to a separatory funnel, and the was added dropwise to a refluxing solution of selenohydroxamic acid organic layer was washed with a saturated solution of NaCl and dried (3.0 g, 17.4 mmol), DMAP (0.168 g), and pyridine (3.5 mL) in over anhydrous MgS04. The solvent was removed by fractional distilbenzene (140 mL) as described for acid chloride 8. After work-up, the lation and the residue was subjected to flash column chromatography to methoxy selenide 14 was obtained in 42% yield as a 4.8:l mixture of eluting remove the by-product, ~-Bu-S~(CH~)~-O-S~(CH~)~-~-BU, two diastereomers. 'H NMR (CDCl,), 6: major diastereomer 8.42 with 10% ether:pentane, then with 25% ether:pentane. Alcohol 1was (m, lH), 7.41 (m, 2H), 7.0 (m, lH), 4.14 (m, lH, CH-0), 3.88 obtained in 46% isolated yield, bp 51.5-53"C/aspirator (lit. (16) lH, CH-Se), 3.35 (s, 3H, 0-CH3), 2.37 (m, lH), 2.1-1.6 (m, bp 78"C/59 Torr); [a]:' - 137.9" (c 1.10, CHCI,); [a]?' - 113.l o (multiplets, 5H). 13cNMR (CDC13), 6: major diastereomer 150.0 (c 1.045, n-hexane). IR (thin film): 3325 (0-H), 3058 (H-C=), (Se-C=N), 135.9, 125.8, 120.3 (pyridyl carbons), 88.4 (CH-0), 1615 (C=C), 1047 (C-0). 'H NMR (CDCI,), 6: 5.88 (m, lH, 44.9 (CH-Se), 31.4, 30.9, 23.1. Anal. calcd. for C11H15NOSe: HC=), 5.75 (m, lH, =HC), 4.77 (m, lH, CH-0), 3.1 (bs, lH, C 51.57, H 5.90, N 5.47; found: C 51.66, H 5.99, N 5.42. -0-H), 2.42 (m, lH), 2.16 (m, 2H), 1.6 (m, 1H). I3C NMR (CDCl,), 6: 134.4 (CH=), 133.2 (=CH), 77.0 (HC-OH), 32.9, Ozonolysis of methoq selenide I4 30.7. The MTPA ester exhibited the following spectroscopic properMethoxy selenide 14 (3.06 g, 11.9 mmol) in CH2C12(75 mL) was ties: 'H NMR (CDC13), 6: 7.57-7.52 (m, 2H), 6.2-6.17 (m, lH, ozonized at -78OC (2.5% ozone) as described for 9. 1-Pentene CH-0), 5.96-5.91 (m, 2H, HC=CH), 3.56 (d, J = 1.2 Hz, 3H, (24.6 mL) in CH2C12(20 mL) was added cautiously to the cold solution 0-CH,), 2.62-2.22 (m, 3H), 1.97-1.8 (m, 1H). ',CNMR (CDC13), and the mixture was added to refluxing pentane. The solvents were 6: 166.3 (C=O), 139.08 (CH=), 129.4, 128.3, 128.0 (=CH), removed by fractional distillation and the residue was distilled under 127.35, 126.2, 120.4,83.03 (CH-0), 55.3 (0-CH,), 31.0,29.48. reduced pressure to yield 3-methoxycyclopentene 2 (68%); [a];' The MTPA ester of the racemic alcohol had the following: 13CNMR -116.9" (c 3.86, n-hexane). 'H NMR (CDCl,), 6: 6.06-6.01 (m, (CDCl,), 6: 166.3 (C=O), 139.21, 139.08, 132.46, 132.32, 129.4, lH, CH=), 5.92-5.86 (m, lH, =CH), 4.51-4.43 (m, lH, CH-0), 128.3, 128.0, 127.35, 127.26, 126.2, 120.4, 83.12, 83.03, 55.3, 3.33 (s, 3H, 0-CH3), 2.56-1.68 (multiplets, 4H, ring CH2's). 31.0, 29.48, 29.35. 13CNMR (CDCl,), 6: 135.7, 130.5 (CH=CH), 86.1 (CH-0), 55.7 (0-CH3), 31 .O, 29.3. Chromatography of 2 using a Ni-4-Pin chiral Methylation of hydroq ester 5 column, isothermal at 60°C and 20psi (1 psi = 6.9 kPa), showed it to A mixture of hydroxy ester 5 (0.5 g, 3.16 mmol), methyl iodide be 98.3% optically pure (97% ee). A sample of 2 prepared by an (0.8 mL, 12.6 mmol), and Ag20 (0.73 g, 3.15 mmol) was refluxed overnight reflux of a mixture of (S)-1 (200 mg), Ag20 (400 mg), and according to the procedure of Mislow (17). After 18 h, 14.2% of 5 methyl iodide (8 mL) was >99% optically pure. remained unreacted. Methyl iodide (1 mL) and Ag20 (0.8 g) were added and the mixture was refluxed for a further 6 h (progress of the Acknowledgements reaction was followed by GC). Ether was added and the mixture was filtered through Celite, and the solvent was removed by fractional The financial support of this work by the Natural Sciences and distillation. Chromatography of the residue over flash silica (eluting Engineering Research Council of Canada is gratefully acknowlwith 15% ether:pet. ether) yielded methoxy ester 11 in 86.4% yield, edged. [a]:' +20° (c 1.311, CHC13). 'H NMR (CDCI,), 6: 4.24-4.0 (16 lines ABX3, 2H, 0-CHI), 3.97-3.88 (m, lH, CH-0), 3.25 (s, 3H, 1. R. K. HILLand A. G. EDWARDS. TetrahedronLett. 3239 (1964). 0-CH3), 2.9-2.74 (8 lines, lH, CH-C02), 2.2-1.47 (m, 6H, ring J. Org. Chem. 2. D. B. DENNEY, R. NAPIER,and A. CAMMARATA. CH2's), 1.22 (t, J = 17.5 Hz, 3H, -CH3). ',c NMR (CDC13),6: 172.6 30, 3151 (1965). (C=O), 84.0 (CH-0), 60.0 (0-CH,), 57.0 (0-CH,), 49.4, Chem. Lett. 389 (1987). 3. M. ASAMIand H. KIRIHARA. 30.4, 25.2, 22.5, 21.9, 14.2. Anal. calcd. for C9HI6o3:C 62.77, V. S. MARTIN, S. S. WOODARD, T. KATSUKI, Y. YAMADA 4. H 9.36; found: C 62.40, H 9.38. M. IKEDA,and K. B. SHARPLESS. J. Am. Chem. Soc. 103, 6237 Hydrolysis of methoq ester 11 (1981). A mixture of methoxy ester 11 (4.186 g, 24.3 mmol), KOH and T. FUJISAWA 5. T. SATO,Y. GOTOH,Y. WAKABAYASHI, (1 1.63 g, 207 mmol), ethanol (34.9 mL), and H20 (186 mL) was Tetrahedron Lett. 4123 (1983). refluxed for 45 min, then it was cooled and extracted with ether. The 6. M. KITAMURA, I. KASAHARA, K. MANABE,R. NOYORI,and aqueous layer was carefully acidified with ice-cold 8% H2SO4 and J. Org. Chem. 53,708 (1988). H. TAKAYA. extracted with ether. Evaporation of ether gave the methoxy acid 12 in 7. (a) K. ALDERand F. H. FLOCK. Chem. Ber. 89,1732 (1956); (b) 95% yield as a 3: 1 mixture of diastereomers accompanied by 1.5% of Tetrahedron, 28,5003 (1972); (c) I. FLEMING and E. J. THOMAS. 1-cyclopentenecarboxalic acid as a by-product. Hydrolysis of 11 J. ISHIYAMA, Y. SENDA,and S. IMAIZUMI. J. Chem. Soc. Perkin (0.5 g) with Ba(OH)2 (2.0 g) and ethanol (8 mL) in H20 (50 mL), Trans. 2, 71 (1982).

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8. K. Mom, H. MORI,and T. SUGAI.Tetrahedron, 41,919 (1985), and references cited. 9. S. TSUBOI,E. NISHIYAMA, M. UTAKA,and A. TAKEDA. Tetrahedron Lett. 1915 (1986). Aust. J Chem. 10. B. S. DEOL,D. D. RIDLEY,and G. W. SIMPSON. 29, 2459 (1976). and C. V. GRUDZINSKAS. J. Org. Chem. 43, 3972 11. A. WISSNER (1978). 12. D. H. R. BARTON,D. CRICH,and Y. HERVE.Tetrahedron, 41, 4347 (1985). and W. VOELTER. Carbon- 13NMR spectroscopy, 13. E. BREITMAIER

14. 15. 16. 17.

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high resolution methods and applications in organic chemistry and biochemistry. 3rd ed. VCH, Weinheim. 1987. p. 2 10. G. GUARTI,L. BANFT,and E. NARISANO. Tetrahedron Lett. 3547 (1986). (a) J. A. DALE,D. L. DULL,and H. S. MOSHER.J. Org. Chem. 34,2543 (1969); (b) M. A. KHAN,D. F. TAVARES, and A. RAUK. Can. J. Chem. 60, 2451 (1982). S. KRISHNAMURTHY andH. C. BROWN.J. Org. Chem. 42, 1197 (1977). K. MISLOW.J. Am. Chem. Soc. 73, 4043 (1951).