Stereoselective Synthesis of Polysubstituted Cyclopropanes from Poly(ethylene glycol)Supported Pyrid

CHEM. RES. CHNESE UNIVERSITIES 2011, 27(6), 984- -987Stereoselective Synthesis of PolysubstitutedCyclopropanes from Poly(ethylene glycol)Supported Pyridinium YlideZHAO Pan', LU Cui-fen', YANG Gui-chun', CHEN Zu-xing',DONG Nian-guo2 and SHI Jia-wei71. Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Ministry of Education,College of Chemistry and Chemical Engineering, Hubei Universit,Wuhan 430000, P. R. China;2.Department of Cardiovarscular Surgery, Union Hospital, Tongji Medical College, Huazhong Science andTechnology University, Wuhan 430072, P. R ChinaAbstract Polysubstituted cyclopropanes were efficiently prepared with poly(ethylene glycoI)(PEG) as soluble sup-port. The reaction of PEG-supported pyridinium ylide with arylidenemalononitrile(R=CN) or ethyl arylidenecyanoa-cetate(R=COOEt) in the presence of triethylamine(TEA) afforded PEG-supported cyclopropanecarboxylates, whichwere cleaved by 1% KCN/EtOH to obtain polysubstituted cyclopropanes with exclusive trans-sclectivity and goodyieldsKeywords Poly(cthylcne glycol); Pyridinium ylide; Synthesis; CyclopropaneArticle ID 1005 -9040(2011)-06 -984-041 Introductionvia the Michael-initiated ring closure strategy is the most usefulmethodology for preparing highly subtituted or functionalizedCyclopropane compounds have been known to exhibitcyclopropanes, and pyridinium ylides, originally prepared byunique reactivity due to their intrinsic ring strain and they canKrohnel2, are commonly used in cycloaddition reactions andconstitute various natural products, biologically active com-have found application in the cyclopropanation reaction, givingpounds, and synthetic intermediatesl- , therefore, cyclopro-product with exclusive trans geometryl23- 26. Our laboratorypanes synthesis has been an attractive subject!s- . The mosthas accumulated abundant experience in soluble polymer sup-important and useful methods for the preparation of cyclopro-ported synthesisl27- -32] and has successfully synthesized indoli-panes include Simmons Smith cyclopropanationf9.10), transi-zines and dihydrofurans using poly(ethylene glycol)(PEG)-tionmetal-mediated carbene transfer from aliphatic diazo com-supported pyridinium ylidel28-321. In conjunction with our recentpounds to carbon carbon double bondsl"I, Michael-initiatedobservations that PEG provides huge steric hindrance to lead toring closure of ylides with electron-deficient olefinsl12-I51, andhigh stereoselectivity in the formation of dihydrofuran deria-base-catalyzed cyclopropanation reaction of a-halogenatedtives via the Michael addition reaction, we have examined thecompounds with electron-deficient olefinsl!6 -21].use of PEG-supported pyridinium ylide for cyclopropane syn-The combination of ylides with electron-deficient olefinsthesis. Herein lies our results (Scheme 1)R、CNR、Ca只:*>+ NCyREsN, CH:CzIwH0O_ KCN,EIOH . HRefluxr”.tAr1B0 ) -OH=PEGs.0Scheme 1 Synthetic routes of target compoundPE30(Aldrich) and PEG-supported compounds were melted2 Experimentalunder vacuum at 80 °C for ca. 30 min before use to remove anytrace of moisture. Melting points were measured on an X-62.1 Materials and Instrumentsdigital melting point apparatus and uncorrected. IR spectraAll organic solvents were dried by standard methods.were recordec中国煤化Ipectrometer(Perin*Corresponding author. E-mail: chzux@hubu.cdu.cnfYHCNM HGReceived December 1, 2010; accepted April 12, 2011.Supported by the National High Technology Research and Development Program of China(No.2009AA03Z420) and theNatural Science Foundation of Hubei Province of China(Nos.2007ABA031, 2008CDA078).No.6ZHAO Pan et al.985Elmer), with NaCI pellets. Mass spectra were recorded on aMS, m/z: 308.05[M门].Finnigan LCQ DUO MS system. 'H NMR(600 MHz) andEthyI trans-2,2-dicyan0-3-(2,3-dimethoxylphenyl)cyclo-'C NMR(150 MHz) spectra were recorded on a Varian Unitypropanecarboxylate(4d): solid, m. p. 107- 110 °C. IR(NaCI),INOVA 600 sectrometer in CDCl3 with tetramethylsiane/cm*': 2872, 2249, 1741, 1635, 1470. 'H NMR(CDCl3, 600(TMS, 0.03%, volume fraction) as internal standard. For X-rayMHz), 8: 7.05(d, IH, F7.8 Hz, ArH), 6.99(d, IH, J=7.8 Hz,crystallographic analysis, the X-ray diffraction intensities andArH), 6.65(d, 1H, J=7.8 Hz, ArH), 4.38- 4.34(m, 2H. CH2).the unit cellparameters were determined on a Bruker3.88(s, 6H, OCH,), 3.75(d, 1H, J=8.4 Hz, CH), 3.06(d, lH,SMART APEX diffractomcter with graphite-monochromatedJ=8.4 Hz, CH), 1.38(4, 3H, CH). 'C NMR(CDCI, 150 MHz),(Mo Ka) radiation(2=0.071073 nm) in a w-2θ scan mode. Dataδ: 170.99, 149.93, 146.02, 132.40, 121.10, 119.41, 11.71,ollction: SMART(Bruker, 2007); cell refinement: SAINT109.74(2C), 60.88, 56.51, 56.40, 32.90, 18.41, 13.91, 5.87. MS,(Bruker, 2007); data reduction: SAINT; program(s) used tom/z: 300.14[M*].solve structure: SHELXS97(Sheldrick, 2008); program(s) usedEthy| trans-2,2- dicyano-3-(3-nitrophenyl)cyclopropane-to refine structure: SHELXL97(Sheldrick, 2008); molecularcarboxylate(4e): solid, m. p.151- -155 °C. IR(NaC), /cm':graphics: SHELXTL(Sheldrick, 2008); software used to pre-2875, 2189, 1743, 1634, 1470. 'H NMR(CDCl], 600 MHz), 8:pare material for publication: SHELXTL.8.29(d, IH, J=7.8 Hz, ArH), 8.17(s, H, ArH), 7.65(d, IH, J=7.8Hz, ArH), 7.23(m, IH, ArH), 4.39- -4.36(m, 2H, CH2), 3.76(d,2.2 Synthesis of Target Compound1H, J=7.8 Hz, CH), 3.19(d, IH, J=7.8 Hz, CH), 1.38(, 3H,A mixture of PEG-supported pyridinium ylide(1, 2.3CH). 'c NMR(CDCI], 150 MHz), 8: 172.56, 147.57, 143.96,mmol), olefins(2, 3.44 mmol), and Et:N(3.44 mmol) in CH2Cl2132.11，129.20, 120.81, 116.76, 108.50(2C), 60.95, 31.21,27.76, 14.01, 5.30. MS, m/z: 300.14[M"].(20 mL) was refluxed for 12 h. After the solvent was evapo-Ethy! trans-2,2-dicyano-3-(4-hydroxylphenyl)eyclopropa-rated under vacuum, the residue was rerstallized in cold Et2O.The precipitate was filtered, washed with cold El2O and driednecarboxylate(4f): oil. IR(NaC1), v/cm-': 2874, 2211. 1746,under vacuum to afford compound 3, which was treated with1630, 1469. 'H NMR(CDCl3, 600 MHz), δ: 7.00(d, 2H, J-8.41% KCN in EtOH(30 mL) and strred at room temperatureHz, ArH). 6.66(d, 2H, J=7.8 Hz, ArH), 5.13(s, 1H, OH),overmight. After evaporation of EtOH, the residue was redis-4.39- 4.36(m, 2H, CH2), 3.76(d, lH, 1=8.4 Hz, CH), 3.08(d,solved in CH2Cl2(3 mL), the detached PEG was precipitated by1H, .J=8.4 Hz, CH), 1.39(t, 3H, CH3). 'C NMR(CDCl3, 150MHz), 8: 171.13, 153.91, 135.77, 126.69(2C), 114.67(2C),adding cold Et2O and was removed by fltration.combined filtrate was evaporated to give crude polysubstituted109.48(2C)，62.11, 31.95, 27.90, 13.49, 5.23. MS, m/z:cyclopropanes, which were purified by column chromatogra-256.09[M].Ethyl trans-2,2-dicyano-3-(4-bromophenyI)cyclopropane-phy on silica gel[V(EA):V(PE)=l:4] to afford pure compoundcarboxylate(4g): oil. IR(NaCI), v/cm': 2872, 2205, 1748,EthyI trans-2,2- dicyano-3-(4-cyanophenyl)eyclopropanc-1628, 1467. 'H NMR(CDCI3, 600 MHz), 8: 8.62(d, 2H, J=8.4carboxylate(4a): oil. IR(NaC), 立/cm': 2882, 2189, 1742,Hz, ArH), 8.54(d, 2H, J=8.4 Hz, ArH), 4.38- 4.36(m, 2H,1634, 1470. 'H NMR(CDCI], 600 MHz), 8: 7.44(d, 2H, J=8.4CH2), 3.72(d, H, J=8.4 Hz CH), 3.35(d, H, J=8.4 Hz, CH),Hz, ArH), 7.26(d, 2H, J=8.4 Hz, ArH), 4.44- 4.40(m, 2H,1.38(t, 3H, CH). 'C NMR(CDCl], 150 MHz), 8: 172.58,CH2), 3.70(d, 2H, J=8.4 Hz, CH), 3.13(d, 2H, J=8.4 Hz, CH),143.02, 131.71(2C), 126.90(2C), 118.92, 108.37(2C), 64.67,1.35(t, 3H, CH3). 'C NMR(CDCl3, 150 MHz), 8: 170.26,32.71, 26.99, 10.57, 9.32. MS, m/z: 318.00[M].147.32, 130.93(2C), 125.98(2C), 114.95, 109.85(2C), 109.43,Ethyl trans-2-cyano-2-ethylacetyl-3-(4-cyanophenyI)cy-clopropanecarboxylate(4h): oil. IR(NaCI), V/cm ': 2875, 2213,61.45, 31.86, 26.94, 14.67, 5.32. MS, m/z: 265.10[M']Ethyl trans-2,2-dicyano 3-(4-methoxylphenyl)cyclopropa-1743, 1640, 1468. lH NMR(CDCl3, 600 MHz), 8: 7.61(d, 2H,necarboxylate(4b): solid, m. p.87- -90 °C. IR(NaCI), V/cm-': .J=8.4 Hz, ArH), 7.37(d, 2H, =8.4 Hz ArH), 4.34- -4.30 (m,2875, 227, 1741, 1629, 1473. 'H NMR(CDCI3, 600 MHz), 8:2H, CH2), 4.06- 4.02(m, 2H, CH2), 3.72(d, H, 5=8.4 Hz, CH),7.25(d, 2H, J=8.4 Hz, ArtH), 6.96(d, 2H, J-8.4 Hz, ArH),3.34(d, H, 1-8.4 Hz CH), 1.35(t, 3H, CH3), 1.09(t, 3H, CH).4.38- -4.36(m, 2H, CH2), 3.84(s, 3H, OCH), 3.65(d, H, J=8.4I3C NMR(CDCI], 150 MHz), 8: 172.33(2C), 147.80, 132.50Hz, CH), 3.09(d, H, J-8.4 Hz, CH), 1.39(, 3H, CH3).(2C), 125.43(2C), 118.98, 116.43, 108.91, 68.76, 58.41, 36.74,'C NMR(CDCl], 150 MHz), 8: 169.09, 156.13, 134.61, 124.3128.10, 8.91(2C). MS, mlz: 312.11[M^].(2C), 112.46(2C), 109.73(2C), 61.90, 55.82, 30.46, 27.80,14.02, 5.22. MS, m/z 270.12[M]cyclopropanecarboxylate(4i): oil. IR(NaCI)， v /cm': 2878,2243, 1735, 1643, 1467. 'H NMR(CDCl], 600 MHz), 8: 7.24(d,Ethyl trans-2,2-dicyano-3-(2,4-dichlorophenyl)cyclopro-panecarboxylate(4c): solid, m. p. 110-113 。C. IR(NaCI),2H, J=8.4 Hz, ArH), 6.89(d, 2H, J=8.4 Hz, ArH), 4.29- 4.26V/cm': 2874, 2226, 1747, 1631, 1468. 'H NMR(CDClz, 600(m, 4H, CH2), 3.62(d. H. J=9.0 Hz. CH). 3.07(d, IH, J=8.4MHz), 8: 7.24(s, H, ArH), 7.12(d, H,JF-8.4 Hz, ArH), 7.10(d, H,Hz, CH), 1.41中国煤化IIR(CDCI3, 150J=-8.4 Hz, ArH), 4.38- 4.35(m, 2H, CH2), 3.67(d, H, J-8.4 Hz,MHz), 8: 173.21iYHC N M H G87(2C), 1.4.CH), 3.06(d, H, J=8.4 Hz, CH), 1.38(, 3H, CH3). "C NMR113.46 (2C), 61.2ucC), 55.4), S2.12, 48.12, 20.26, 13.98(2C).(CDCI], 150 MHz), 8: 172. I0, 137.63, 132.61, 130.92, 128.92,MS, m/z: 317.14[M']127.88, 126.58, 109.67(2C), 62.45, 32.98, 19.57, 13.87, 5.67.Ethyl trans-2-cyano-2-ethylacetyl-3-(2,4-dichlorophenyI).cyclopropanecarboxylate(4j): oil. IR(NaCI), 0 /cm': 2876,986CHEM. RES. CHINESE UNIVERSITIESVol.272211, 1753, 1654, 1468. 'H NMR(CDCl3, 600 MHz), 8: 7.42(s,fully characterized by 'H NMR and 3C NMR, MS, IR1H, ArH), 7.25(d, lH, J=7.8 Hz, ArH), 7.16(d, H, J-8.4 Hz,single X-ray diffaction. The 'H NMR data of the preparedArH), 4.13- 4.11(m, 4H, CH2), 3.63(d, 1H, =8.4 Hz, CH),cyclopropanes all show that only the trans product was ob-3.27(d, 1H, J-8.4 Hz, CH), 1.40- -1.38(m, 6H, CH,). "C NMR(CDCl3, 150 MHz), 8: 170.96, 163.02, 137.21, 132.42, 130.88,lopropane vicinal proton coupling constant of ca. 8.4 Hz201.128.55, 127.99, 126.01, 115.35, 60.85(2C), 30.82, 19.91, 18.21,For example, the 'H NMR spectrum of compound 4a shows13.93(2C). MS, m/z: 355.05[M].wo doublets at 8 3.70 and 3.13, respectively, with a couplingEthyl trans-2-cyano-2-ethylacetyl-3-(2,3-dimethoxylphe-constant 上8.4 Hz for protons at 1,3-position. And compoundnyl)cyclopropanecarboxylate(4k): oil. IR(NaCI), V/cm ': 2873,4b displays these two protons at 8 3.65 and 3.09, with the same2250, 1739, 1645, 1468. 'H NMR(CDCl3, 600 MHz), 8: 7.03(d,coupling constant. As an example the structure of compound 4dH, J=7.8 Hz, ArH), 6.94(d, H, J=7.8 Hz, ArH), 6.68(d, H,J=7.8was confirmed by single X-ray diffraction(Fig.1). It should beHz ArH), 4.37- -4.36(m, 4H, CH2), 3.88(s, 6H, 0CH3), 3.75(d,pointed out that the X-ray determination of compound 4dH, J-8.4 Hz, CH), 3.12(d, H, J=8.4 Hz, CH), 1.37(L, 3H, CHs),clearly displays that the two substituents at the 2,3-position of1.15(t, 3H, CH3). 'C NMR(CDCI, 150 MHz), 8: 172.94(2C),cyclopropane are at anti-position. On the basis of these facts,148.43, 145.97, 131.45, 120.55, 118.47, 118.02, 110.98, 69.82,we could conclude that cyclopropanes prepared by this proce-57.86, 56.32(2C), 27.54(2C), 26.84, 9.31(2C). MS, m/z: 347.12dure were in diastereomerically trans-configuration, which[M]might display that the stereochemical outcome of this reactionEthyltrans-2-cyano-2- ethylacetyl-(3-nitro-phenyl)cy-is thermodynamic control.clopropanecarboxylate(4): oil. IR(NaC), /cm ': 2875, 2231,H8B1750, 1651, 1472. 'H NMR(CDCI, 600 MHz), 8: 8.26-C5HH8A8.19(m, 2H, ArH), 7.67- -7.61(m, 2H, ArH), 4.10- -4.07(m, 4H,.6C3 /c8 H8CCH), 3.75(d, 1H, J=8.4 Hz, CH), 3.19(d, IH, JF-8.4 Hz, CH),，HI。 NIy_C2021.40- -1.28(m, 6H, CH3). BC NMR(CDCl3, 150 MHz), 8:;。HI6BcSI2 H7B171.13, 162.55, 146.23, 139.20, 135.13, 126.69(2C), 121.15,H16AR4C9o HI7A115.37, 61.15(2C), 30.95, 19.95, 13.49(2C). MS, m/z. 332.14H9oil[M].HISBH7CHI5AEthyl trans-2-cyano-2-ethylacetyl-3-(4-hydrox-ylphenyI)cyclopropanecarboxylate(4m): oil. IR(NaC), V/cm^': 2874,Fig.1 Molecular structure of compound 4d in2210, 1743, 1639, 1467. 'H NMR(CDCI, 600 MHz), 8: 7.02(d,the crystal2H, J-8.4 Hz, ArH), 6.64(d, 2H, J=7.8 Hz, ArH), 4.33(m, 4H,The mechanism involving selectivity can tentatively beCH2), 3.72(d, H, J=8.4 Hz, CH), 3.18(d, H, 5=8.4 Hz, CH), .1.36(t, 3H, CH3), 1.14(, 3H, CH). 'C NMR(CDCl3, 150assumed as Scheme 2. The first step is the formation of an eno-late A via deprotonation of the pyridinium salt by Et;N. TheMHz), 8: 172.35(2C), 154.32, 135.76, 126.68(2C), 115.43(2C),119.27, 68.97, 57.86, 35.86, 27.41(2C), 9.36(2C). MS, m/z:enolate A, in which the large pyridyl and poly(ethylene glycol)groups are in trans relationship, is expected to be predominant303.11 [M]upon deprotonation due to both steric factors and electrostaticEthyl trans-2-cyano-2-ethylacetyl-3-(4-bromopheny)ey-clopropanecarboxylatec(4n): oil. IR(NaC), v/cm^': 2876, 2217,interaction between the cationic pyridine and anionic carbonmoieties. The second step is a Michael addition of enolate A to1739, 1641, 1472. 'H NMR(CDCl3, 600 MHz), 8: 7.46(d, 2H,the olefins to form a new carbanion intermediate B. The lastJ=7.8 Hz ArH), 7.14(d, 2H, =7.8 Hz, ArH), 4.35- -4.32(m,step is the intramolecular substitution of the carbanioin fo2H, CH2), 4.08- -4.05(m, 2H, CH2), 3.66(d, 1H, J=7.8 Hz, CH),pyridine and the formation of PEG-supported cyclopropane-3.3(d, 1H, J=-8.4 Hz, CH), 1.37(t, 3H, CH3), 1.11(1, 3H, CH3).carboxylates. In the last cyclization step, the bucky aryl andBC NMR(CDCl, 150 MHz), 8: 172.06, 162.21， 143.13,PEG supported group would prefer anti position, which subse-131.74(2C)，129.88(2C), 112.90, 114.87, 62.64(2C), 31.99,quently caused the formation of cyclopropanes with diastereo-27.91, 20.70, 14.13(2C). MS, m/: 365.04[M].merically trans-configuration.3 Results and DiscussionREIN. 0As shown in Scheme 1， PEG-supported pyridiniumA2Aylide(1) prepared from PEG3400 as previously reportedl28 3reacted with olefins(2) at refluxing temperature in dry CH2Cl2RVCNwith EtzN as a base, obtaining PEG-supported cyclopropane-R、CNcarboxylates(3) as brown powder. Olefins(2) was easily pro-中国煤化工)地!duced by the Knoevenagel condensation of aromatic aldehydesCHAr'CNMHGand malononitrile, ethylcyanoacetic ester. Finally the polysubs-4TYHtituted cyclopropanes(4) were obtained by treating compound33Bwith I% KCN in dry EtOH at room temperature ovemight.Scheme 2 Plausible mechanism involving selectivityThe structures of all the obtained cyclopropanes wereof forming compound 3No.6ZHAO Pan et al.987Initial attempts worked perfectly with 4-(2,2-dicyanovi-[3] Wong H. N. c.. HonM. Y,, TseC. W, Yip y. C., Chem. Rev, 1989.ny)benzonitrile(2a) and PEG-supported pyridinium ylide(1)89,165and ethyl trans-2,2-dicyano-3-<(4-cyanophenyl)cyclopropane-[4] SaluN.J, Chem. Rev. 1989. 89, 1247carboxylate(4a) was formned in a yield of 82%(based on the[5] Lebel H., Marcoux J. F, Molinaro C, Charette A. B.. Chem. Rev,loading capacity of PEG). To probe into the generality of this2003, 103, 977finding, we exlended the investigation to a number of sub-[6] Kulinkovich 0. G., Mejere D. A. Chem. Rev, 200 100. 2789strates with results summarized in Table 1. .7] Burgess K, Ho K K, Sherman M. D, Sylett, 1994.575Table 1 Synthesis of polysubstituted cyclopropanes[8] StammerC. H., Terahedron, 1990. 46. 2231from PEG -supported pyridinium ylide[9] Hoveyda A. H.. Evans D. A, FuG. C, Chem Rev. 1993. 93, 1307Compound10] Nicolas L, Le Maux P, Simonncaux G., Coord Chem. Rev, 2008,48C252, 7274tCN4CH;OC&H411] Pllssier H, Tetrahedron, 2008, 64, 70412.4-CIhCoH337[12] Sun x. L. Tang Y., Acc. Chem. Res,. 2008, 41, 9372.3-(0CH)2C&Hs[13] Peppe C., Chagas R. P, Burrow R A, J. Organomet. Chem. 2008,3-NO2C&H4693, 34414HOC&H435[14] RenZ.J, Cao W. G., Ding W. Y, Wang Y. Wang L. L.. Synth.4-BrC&H436Commun, 2004, 34, 3785COOEt4-CNC&H46015] RenZ. J. Cao w. G, Chen J, Wang Y, Ding W. Y, Synth. Com-4-CH;OCH4mun, 2005, 35, 30992.4-CICH;30[16] WangQ. F. Song X. K., Chen J, YanC. G,J. Comb. Chem. 2009,2.3-<0CH)2C&H37611, 1003-NO:CH34[17] Arai s, Nakayama K, Hatano K.. Shioiri T.J Org. Chem, 1998.,4n4-HOCcH48354, 9572[18] Arai s., Suzuki Y, Nakayarma K, Hatano K, Shiori T, Tetrahe-dron Lett, 1998. 39, 9739Compared to conventional liquid synthesis methods, this[19] Arai s. Nakayama K, Ishida T., Shioiri T.. Tetrahedron Lett, 999,method has a number of advantages including high yield,40, 4215simple purification and absence of competing side reactions,[20] Miyagawa T, Tatenuma T, Tadokoro M, Satoh T, Tetrahedron,which are all based on the features of PEG supported synthesis.2008. 64, 5279Otherwise, the PEG supported group provides huge steric hin-[21] Elinson M. N, Feducovich s. K, Vereshchagin A. N., Gorbunov S.drance to restrict enolate to attack carbon in a certain direction,v, Belykov P. A. Nikishin G. L, Tetrahedron Let.2006. 47, 9129thus leading to high stercosclectivity. PEG-supported products[22] Kr8hnke F. Ber. Deu. Chem. Ges. 1935. 68.1177can be conveniently rerystallized in cold ethyI ether, and the[23] Shestopalov A. M. Sharanin Y. P., Litvinov V. P, Nefedov O. M,by-products are removed by simple fltratin, which simplifesZh. Org. Khim, 1989, 25, 111the purification a lot.[24] Shestopalov A. M.. Litvinov V. P. Rodinovskaya L. A, Sharanin Y.A. lzv. Acad Nauk SSR, Ser. Khim. 1991,1, 1464 Conclusions[25] Litvinov v. P., Shestopalov A M. zh Org Khim, 1997, 3975We have presented the efficient synthesis of trans-[26] Eyermann C. J. Vo N. H, Hodge C. J, Terahedron Letl. 1997, 38,polysubstituted cyclopropanes via the reaction of PEG-7951supported pyridinium ylide with arylidenemalononitrile(R= CN)[27] Zhang H. Q.. Yang C C, Chen J. N, Chen z. x, Sythesis, 2004,or ethyl arylidenecyanoacetate(R=COOEt). All the reactions18, 3055proceeded under mild conditions and gave the products in ex-[28] Chen z. x, Yue G. z., Syletrt. 2004, 1231clusive trans-seletity and good yield. The separation and[29] Yue G. Z., Chen Z. X., Bioorg. & Med Chem Let., 2005, 15, 453[30] Huang Y. L, LuC. F, Chen Z. X, Yang G. C, J. Heterocyecliepurification processes are very simple and convenient.Chem, 2007, 44, 1421[31] Xie H. W., LuC. F., Chen z. X., Yang G. C, Synthesis, 2009, 2, 205References[32] Feng C, LuC. F. Chen z. Xx, Dong N. G, ShiJ W, Yang G, C,J.[I] Meijere D. A.. Chem. Rev.. 2003, 103, 931Heterocyelic Chem, 2010, 47, 671[2] Rappoport z, The Chemistry of the Cyelopropyl Group, Wiley, NewYork, 1987, 12, 521中国煤化工MHCNMHG