Diels-Alder reactions of 5,5,5-trichloro-3-penten-2-one and ethyl 4,4,4-trichloro-2-butenoate with cyclopentadiene in the presence of a chiral Lewis acid gave exo-2-acetyl-endo-3-trichloromethyl-bicyclo[2.2.1]hept-5-ene and exo-2-ethoxycarbonyl-endo-3-trichloromethylbicyclo[2.2.1]hept-5-ene with 40% and 7% e.e., respectively

Nakatsu, Shogo

Tsuboi, Sadao

Okayama University Digital Information Repository

Asymmetric Diels-Alder Reaction of 5,5,5-Trichloro-3-penten-2-one and Its Related Compound

Okayama University Scientific Achievement Repository

afTm:Ied exo-2-acetyl-endo-3-trichloromethyl-And the Diels-Alder reaction of ethylafTm:Ied exo-2-ethoxycarbonyl-endo-3-trichloro-Journal of the Faculty of Environmental Science and Technology,Okayama UniversityVo1.9, No.1, pp.163·166, February 2004Asymmetric Diels-Alder Reaction of 5,5,5-Trichloro-3-penten-2-one and Its Related CompoundShogo Nakatsu and Sadao Tsuboi*(Received December 2. 2003)Diels-Alder reactions of 5,5,5-trichloro-3-penten-2-one and ethyl 4,4,4-trichloro-2-butenoatewith cyclopentadiene in the presence of a chiral Lewis acid gave exo-2-acetyl-endo-3-trichloromethyl-bicyclo[2.2.1]hept-5-ene and exo-2-ethoxycarbonyl-endo-3-trichloromethylbicyclo[2.2.1]hept-5-enewith 40% and 7% e.e., respectively.key words: asymmetric reaction, Diels-Alder reaction, asymmetric Diels-Alder reaction, chiralLewis acid, trichloromethyl group1. INTRODUCTIONDiels-Alder reactionl , 2 is a most popular [2+4] cycloaddition reaction. Asymmetric Diels-Alder reactionsl ,2 by theuse of chiral Lewis acid catalysts3-6 containing elements such as boron,7 aluminum,S titanium,9 and magnesium etal. 10 are well known.We reported a convenient synthesis of 5,5,5-trichloro-3-penten-2-one (1) and ethyl 4,4,4-trichloro-2-butenoate (2)by the reaction of 1,3-dicarbonyl compounds with chloral in the presence of potassium carbonate. 11 Compounds 1and 2 are good dienophiles because of the presence of trichloromethyl and carbonyl groups. In 1974, we reported theDiels-Alder reaction of 1 with some dienes. 12Here we report asymmetric Diels-Alder reaction of 1 and 2 with cyclopentadiene in the presence of a chiral Lewisacid.2. RESULTS AND DISCUSSIONThe Diels-Alder reaction of 1 with cyclopentadienebicyclo[2.2.1]hept-5-ene (3) with high stereoselectivity.124,4,4-trichloro-2-butenoate (2) with cyclopentadiene alsomethylbicyclo[2.2.1]hept-5-ene (4) predominantly.The reaction of 1 with cyclopentadiene in the presence of a chiral Lewis acid: (R)-MS-free BINOL-Ti13 gave thecycloaddition product 3 in a good yield with 40% e.e. The reaction of 2 with cyclopentadiene in the presence of(R)-MS-free BINOL-Ti was also tried to give the cycloaddition product 4 with 7.0% e.e.*Department of Environmental Chemistry and Materials, Faculty of Environmental Science and Technology, OkayamaUniversity, Okayama 700-8530, Japane-mail: stsuboi6@cc.okayama-u.ac.jp163164 J. Fac. Environ. Sci. and Tech., Okayama Univ. 9 (1) 20041, Y =CH 32, Y =OC2Hs+ o ~(R)-MS-free BINOL-Ti(0.047 eq)r.t.,39h3, Y =CH 3 : 85% yield; 40 % e.e.4, Y =O~Hs: 38% yield; 7.0 % e.e.(R)-BINQ.-Ti =MS: molecular sieves4A3. EXPERIMENTALAll IR spectra were recorded on a JASCO Ff/IR-5000 infrared spectrophotometer as films. lH NMR (200 MHz& 500 MHz) spectra and B C NMR spectra were recorded on a Varian Gemini-200 spectrometer or Varian Gemini-500spectrometer using CDCl3 (CHCI3 , () =7.26) as a solvent unless otherwise noted ani chemical shifts are given inppm relative to CDCl3 (7.26 ppm for lH NMR and 77.0 ppm for 13C NMR). lH NMR (300 MHz) and B C NMR (75Mz) spectra were recmIed on a JEOL A1300 spectrometer. Splitting patterns are designated as br, s, d, t, ani m;these symbols indicate broad, singlet, doublet, triplet, and multiplet, respectively. Elemental analysis were performedon Perkin Elmer 2400 series II CHNS/O analyser. For thin layer chromatography aluminum sheets Merck silica gelcoated 60 F254 plates were used and the plates were visualized with UV light and phosphomolybdic acid (5% inEtOH). Merck silica gel 60 N (spherical, neutral) (40-50 tLm) was used for the flash chromatography. The progressof the reaction was monitored by GC-MS Shimazu QP 5000 at 70 ev. Some stereoisomers of synthesized olefin wereseparated by preparative GC (Yanagimoto G-2800): column (6/5 mmp x 2 m) packed with 10% liq. phase ApiesonGrease L supported on chromosorb W. Enantiomeric excess was determined by GC analysis: Shimazu GC-18A;column (0.25 mmcj> x 60 m) packed with CYCLODEXB at 170 °c, carrier gas; He (17 ml/sec).All reactions were carried out in oven-dried, septum-capped flasks under Nz. All liquid reagents were transferredvia oven dried syringes. Solvents and reagents were dried and distilled before use. THF was distilled fromNa-benzophenone ketyl before use.5,5,5-Trichloro-3-penten-2-one (1).11In a typical experimental procedure, 1.30 g (9.38 mmol) of anhydrous potassium carbonate and 0.64 mL (6.25mmol) of 2,4-pentanedione in 5 mL of anhydrous THF were placed in a 10 mL round bottomed flask. To thismixture, 0.73 mL (7.5 mmol) of chloral was ldJaj at room temperature via syringe under Nz atmosphere. After 2days, the reaction mixture was diluted with 10-15 mL of water and extracted with ether (20 mL x3). After removal ofthe solvent, the residue was subjected for column chromatography over silica gel using hexane and then hexane-ethylacetate (l0-12%) as an eluent to furnish the title compound as an yellow oil: the ketone 1 (0.867 g) (74%)S. Nakatsu et al. / Asymmetric Diels·Alder Reaction of 5, 5, 5· Trichloro·3-penten-2·one and Its Related Compound(ElZ=I00/0); Rf 0.45 (hexane/EtOAc, 4/1); IR (neat) v 3044, 3012, 1709, 1682, 1630, 1427, 1363, 1305, 1267,1255, 1174, 1096, 1046, 1023, 1002,965, 911,853, 768, 729 cm,l; IH NMR (200 MHz, CDCI3) b 2.37 (s, 3H),6.59 (d, J = 15.0 Hz, IH), 7.03 (d, J = 15.0 Hz, IH); I3C NMR (SO MHz, CDCI3) b 28.79, 92.58, 128.0, 144.3,196.5.Ethyl 4,4,4-Trichloro-2-butenoate (2).11Potassium carbonate (43.7 g, 0.316 mol) was placed in a 300 ml round bottom flask, and dry THF (167 ml) wasadded. To a stirred mixture was added ethyl benzoylacetate (36.0 ml, 40.0 g, 0.208 mol) and chloral (25.0 ml, 38.0g, 0.258 mol). The mixture was stirred at room temperature for 6 days, and then poured into water. The organic layerwas extracted with ethyl acetate, and dried over MgS04• After removal of the solvent, the residue was distilled to givea colorless oil (36.7 g, 81.2%) at 85-86°C/1O mmHg; Rf 0.60 (hexane/EtOAc, 411); IR (neat) v 2986 (C-C), 1729(ester C=O), 1657 (C=C), 1468 (C=C), 1448 (C=C), 1396 (C=C), 1371 (C=C), 1309 , 1276 , 1183, 1096, 1033,965, 866, 816, 774cm·l; IH NMR (200 MHz, CDCI3) b 1.33 (3H, t, J = 7.0 Hz, OCH,CH3), 4.27 (2H, q, J = 7.0Hz, OCH,CH3), 6.39 (1H, d, J= 15.0 Hz, CI3CCH=CID, 7.22 (IH, d, J= 15.0 Hz, CI3CC!i=CH); I3C NMR (50MHz, CDCI3) b 14.13,61.54,92.16,121.70,146.01,164.70.Diisopropoxytitanium (IV) Dichloride.14To a solution of titanium(lV) isopropoxide (4.5 ml, 15.2 mmol) in hexane (14 ml) was added titanium(IV) chloride(1.7 ml, 15.4 mmol) slowly at room temperature. On addition of titanium(lV) chloride, heat was evolved. Afterstirring for 10 min, the solution was allowed to stand for 6 h at room temperature, aOO the precipitate was thencollected. The precipitate was washed with hexane (5 ml x 2) and recrystallized from hexane (5 ml). The wet powder(1.96 g) was dried under reduced pressure to give 1.93 g of white powder, which was dissolved in toluene (27.2 ml) togive a 0.3 M toluene solution.(R)-MS-free BINOL-Ti.13A 100 ml round-bottomed flask equipped with a magnetic stirring bar aOO nitrogen inlet was charged withpowdered molecular sieves 4A (15.95 g), (R)-(+)-binaphthol (0.838 g, 2.93 mmol), aOO 52 ml of dichloromethane.After the mixture was stirred for 20 min at ambient temperature, the above solution (0.3 M, 10 ml) ofdiisopropoxytitanium dichloride in toluene was added into the resulting suspension in one portion. At this point, thereaction mixture became a red-brown suspension. After being stirred for 1.5 h at that temperature, the resultantsuspension was transferred with syringe to a centrifugating tube capped with a rubber septum. By centrifugation at4000 rpm for 20 min, molecular sieves were sedimented. The resultant supernatant was transferred with syringe to a100 ml round-bottomed flask. The mixture was evaporated at O°C to room temperature under reduced pressure to givea deep reddish residue. The resulting residue was suspended by adding 30 ml of hexane. The suspension was stirred for20 min, aOO hexane was then decanted with a syringe. The resulting precipitate was vacuum-dried to give thebinaphthol-titanium complex (0.67 g, 56.7% yield) and used as a catalyst.exo-2-Acetyl-endo-3-trichloromethylbicyclo[2.2.I]hept-S-ene (3).12To a toluene solution (4 ml) of 5,5,5-trichloro-3-penten-2-one (I) (0.396 g, 2.11 mmol), the (R)-MS-freeBINOL-TiI3 (42 mg, 0.10 mmol, 0.047 eq) was added at room temperature. After 5 min, cyclopentadiene (0.33 ml,3.98 mmol) was <died in the reaction mixture. After being stirred for 38.5 h at room temperature, the resultantmixture was diluted with ether and brine. The organic layer was extracted three times with ether. The extract was driedover MgS04 aOO the solvent was evaporated under reduced pressure. Separation of the residue by silica gel columnchromatography (hexane/EtOAc,lO/I) gave 0.456 g (85.3%) of 3 as an yellow oil: IR (neat) 2984, 2361, 1711,1682, 1630, 1453, 1365, 1265, 1247, 1173 cm,l; IH NMR (200 Mz, CDCI3) b 1.45 (dq, IH, J = 8.9 Hz, J = 1.8Hz, Hs), 1.73 (dbs, IH, J = 8.8 Hz, H7), 2.32 (s, 3H, exoCOCH3), 2.65 (dd,J = 5.6 Hz, J = 1.6 Hz, Hz), 2.95 (bs,165166 J. Fac. Environ. Sci. and Tech., Okayama Univ. 9 (1) 2004I3CIH, HI)' 3.29 (bs, IH, ~), 4.02 (<kl, lH, J =5.6 Hz, J =3.0 Hz, H3), 6.29 (t, 2H, Hs and 110, J =13.4 Hz) ;NMR (50 MHz, CDCl3) b 30.10, 47.28, 47.69, 48.44, 56.03, 63.35, 101.8, 135.4, 135.7,207.1; [a]ZJ.7D=-38.0 (c=1.0, CHCl3); e.e. =40%.exo-2-Ethoxycarbonyl-endo-3-trichloromethylbicyclo[2.2.1 ]hept-S-ene (4).To a toluene solution (4 ml) of ethyl 4,4,4-Trichloro-2-butenoate (0.447 g, 2.06 mmol), the (R)-MS-freeSINOL-Ti 13 (39 mg, 0.097 mmol, 0.047 eq) was added at room temperature. After 5 min, cyclopentadiene (0.33 ml,3.98 mmol) was added to the reaction mixture. After being stirred for 58 h at room temperature, the resultant mixturewas diluted with ether and brine. The organic layer was extracted three times with ether. The extract was dried overMgS04 and the solvent was evaporated under reduced pressure. Separation of the residue by silica gel columnchromatography (hexane/EtOAc, lOll) gave 0.223 g (38.1%) of 4 as a pale yellow oil: IR (neat) 2983, 2360, 1731,1456, 1394, 1376: 1249, 1178 cm'l; IH NMR (300 Mz, CDCI3) b 1.29 (t, 3H, J =7.2 Hz, CH3), 1.51 (dq, lH, J =8.7 Hz, J =1.8 Hz, Hg), 1.89 (d, IH, J =8.7 Hz, H7), 2.44 (dd, IH, J =6.0 Hz, J =1.8 Hz, Hz), 3.04 (bs, IH, HI),3.34 (bs, lH, ~), 3.93 (<kl, IH, J =5.7 Hz, J =3.0 Hz, H3), 4.21 (dq, 2H, J =7.0 Hz, J =2.4 Hz, CHz), 6.27 and6.27 (<kl, 2H, J =15.9 Hz, J =5.7 Hz, J =3.0 Hz, Hs and 110); 13C NMR (75 MHz, CDCI3) b 14.21,47.38, 48.29,48.66,49.46,61.10,64.98,101.6,135.1,135.9,173.9. [atZ.6D= -20.6 (c 1.1, CHCI3); e.e. =7.0%.ACKNOWLEDGEMENTS: We thank SC-NMR Laboratory of Okayama University for the measurement ofNMR spectra.REFERENCES1. Cycloaddition Reactions in Organic Synthesis; Kobayashi, S; Jogensen, K A., Ed.; WILEY-VGI Verlag GmbHWeinheim: Germany, 2002.2. The DIELS-ALDER REACTION; Fringuelli, F.; Taticchi, A., Ed.; WILEY-VGI Verlag GmbH Weinheim: Germany,2002.3. Lewis Acid Reagents -A Practical Approach-; Yamamoto. H., Ed.; Oxford university press: London, 1999.4. Encyclopedia of reagents for organic synthesis; Paquette, L. A., Ed.; John Wiley & Sons, Chichester, New York,Brisbane, Toronto, Singapore, 1995.5. Selectivities in Lewis acid promoted reaction, Schinzer, D., Ed.; Kluwer Academic Publishers, Dordrecht, Boston,London, 1988.6. Lewis acids and selectivity in organic synthesis, Sasntelli, M.; Pons, J.-M., Ed.; CRC press: BocaRaton, New York,London, Tokyo, 1996.7. (a) Ishihara, K; Kurihara, H.; Yamamoto, H. J. Am. Chem. Soc. 1996, 118,3049. (b) Ishihara, K; Kurihara, H.;Matsumoto, M.; Yamamoto, H. J. Am. Chem. Soc. 1998, 120, 6920. 8. (a) Bao, J.; Wulff, W. D.; Rheingold, A. L. J.Am. Chem. Soc. 1993, 115,3814. (b) Bao, J.; Wulff, W. D.; Dominy, J. B.; Furno, M. J.; Grant, E. B.; Rob, A. C.;Whitcomb, M. c.; Yeung, S.-M.; Ostrander, R. L.; Rheingold, A. L. J. Am. Chem. Soc. 1996, 118, 3392.9. Motoyama, Y.; Terada, M.; Mikarni, K Synlett, 1995,967.10. (a) Desimoni, G.; Faita, G.; Righetti, P. P. Tetrahedron Lett., 1996,37,3027. (b) Carbone, P.; Desimoni, G.; Faita,G.; Filippone, S.; Righetti, P. P. Tetrahedron, 1998,54,6099.11. (a) Tsuboi, S.; Uno, T.; Takeda, A. Chem. Lett., 1978, 1325. (b) Nakatsu, S.; Tsuboi, S. Tetrahedron, 2004, 60,No. 10, in press.12. Tsuboi, S.; Ishiguro, Y; Takeda, A. Bull. Chem. Soc. lpn., 1974,47,1673.13. Mikami, K; Motoyarna, Y.; Terada, M. J. Am. Chem. Soc. 1994, 116, 2812.14. Mikami, K; Terada, M.; Nakai, T. J. Am. Chem. Soc. 1990, 112,3949.

Asymmetric Diels-Alder Reaction of 5,5,5-Trichloro-3-penten-2-one and Its Related Compound

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