2006年第26卷有機(jī)化學(xué)第9期,1306~1308Chinese Joumal of Organic ChemistryNo.9.1306~1308·研究簡(jiǎn)報(bào)·聚乙二醇(400中的不對(duì)稱 Baylis-Hillman反應(yīng)丁益萍丁沈宗旋李斌張雅文*(蘇州大學(xué)化學(xué)化工學(xué)院江蘇省有機(jī)合成重點(diǎn)實(shí)驗(yàn)室蘇州215123摘要從易得的L脯氨酸出發(fā),方便地合成了氨基醇1.以聚乙二醇(400為溶劑,考察了手性氨基醇1(30mo%)在聚乙二醇(400中催化不對(duì)稱的 Baylis- Hillman反應(yīng),有較好的催化活性和立體選擇性,產(chǎn)率最高達(dá)954%,ee值最高達(dá)543%.手性氨基醇1聚乙二醇(40)催化體系可方便回收并重復(fù)利用,在前三次循環(huán)中,未發(fā)現(xiàn)反應(yīng)產(chǎn)率和選擇性有明顯變化關(guān)健詞不對(duì)稱 Baylis-Hillman反應(yīng);手性氨基醇;循環(huán)使用;聚乙二醇(400Asymmetric Baylis-Hillman Reaction in Poly(ethyleneglycol)(400)DING, Yi-Ping DING, Yi SHEN, Zong-Xuan LL, Bin ZHANG, Ya-Wen"(Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry and Chemical EngineeringSuzhou University, Suzhou 215123)Abstract Chiral amino alcohol 1 was prepared from L-proline conveniently. In poly (ethyleneglycol(PEG)(400), this chiral amino alcohol (30 mol%)catalyzes asymmetric Baylis-Hillman reaction effectivelyHigh yields(up to 95.4%)and modest selectivities(up to 54.3% ee)were achieved. The chiral amino alco-hol-PEG(400)catalytic system could be easily recovered and reused in the next run. No significant changesin the reaction yields and selectivities were found in the first three runsKeywords asymmetric Baylis-Hillman reaction; chiral animo alcohol; recycling, PEG(400)近來(lái),有機(jī)小分子催化劑催化的有機(jī)反應(yīng)引起了越基醇結(jié)構(gòu)的光學(xué)活性叔胺用于 Baylis-Hillman反應(yīng),探來(lái)越多的化學(xué)工作者的關(guān)注L脯氨酸是一種有效的手討了這類催化劑的不對(duì)稱誘導(dǎo)效果,獲得了e值為2%~性催化劑,可以高立體選擇性地催化Aldo, Mannich和27%的產(chǎn)物,其中奎尼定效果較好. Marko還研究了在Michael反應(yīng)L脯氨酸的衍生物氨基醇類化合物也可以不同壓力下,奎尼定的催化效果,得到ee值為6%有效地催化一些有機(jī)反應(yīng)45%的產(chǎn)物.近來(lái), Iwabuchi等研究了奎尼定及其衍Baylis-Hillman反應(yīng),由 Baylis和 Hillman于1972生物催化的不對(duì)稱 Baylis-Hillman反應(yīng),得到a亞甲基年首次在專利中報(bào)道它是指活化烯的a位和含有缺電B羥基酯和26-二(對(duì)硝基苯基)5亞甲基-1,3-二氧雜環(huán)子sp2碳的親電試劑在胺類催化劑,如叔胺的作用下形已4酮的混合物,對(duì)其中具有較好不對(duì)稱誘導(dǎo)效果的碳一碳鍵,并生成具有多個(gè)官能團(tuán)分子的反應(yīng),這一奎尼定衍生物QD4進(jìn)行了較詳細(xì)的研究和機(jī)理的探討反應(yīng)具有選擇性好、原子經(jīng)濟(jì)性、反應(yīng)條件溫和以及產(chǎn)中國(guó)科學(xué)院上海有機(jī)化學(xué)研究所施敏等在這一反應(yīng)的物引入多種官能團(tuán)等優(yōu)點(diǎn)凹. Brzezinski等國(guó)用(R-3-研究中,做了不少有意義的工作.他們用喹尼定衍生物quinuclidinol催化丙烯酸甲酯和乙醛的反應(yīng)僅獲得e4(3中國(guó)煤化工03decs- yI)quinolin值為10%的產(chǎn)物與此同時(shí),人們還發(fā)現(xiàn)尸氨基醇作為6-oCNMHG(Eq1),反應(yīng)表現(xiàn)出催化劑能大大提高反應(yīng)速度.Mako等將一些具有氨較好的選擇性;使用這一催化劑,他們用磺酰亞胺代替E-mail:zhangyw@suda.edu.cnReceived September 5, 2005; revised December 6, 2005; accepted March 27, 2006.No 9丁益萍等:聚乙二醇(400中的不對(duì)稱 Baylis-Hillman反應(yīng)1307chiral12催化劑{S-1(S-1-甲基四氫吡咯]甲基}四氫吡amino-alcohol(1)咯2}-甲醇(1)的合成以L脯氨酸為原料,用焦碳酸二叔丁酯對(duì)氨基進(jìn)行保護(hù),二環(huán)己基碳二亞胺接肽,四氫鋰鋁還原得1,三步總產(chǎn)率72.8%(文獻(xiàn)值為75%).[a-150(c2.0,CHCI3);H NMR(CDCl3)8: 1.59-1.97(m, 8H, 3-CH23'CH2,4CH2,4CH,2.17~2.54(m,7H,3-cH2,(+r-quinidineToo3CH2,CH3),2.60~272(m,2H,2CH,2CH,3.07(t醛,在一30℃下與甲基乙烯基酮或丙烯酸酯反應(yīng),得到78出lCH),317(d,J=92,52Hz1HCH2了很好的結(jié)果336(dd,J=104,36H,1H,OCH2),3.56(dd,J=10.8,Baylis-Hillman反應(yīng)的缺點(diǎn)是對(duì)于某些底物,反應(yīng)28H1H,OCH,454(s,H,OH; C NMR(CDC3)度太慢,轉(zhuǎn)化率低,造成它在合成上應(yīng)用的局限性.2325,2461,28.08,2995,41.59,5695,57.82,5880,2004年, Chandrasekhar報(bào)道了聚乙二醇400中1,4=63.82,6.28,6085. HRMS m(%:284.0785(10,cald氮雜雙環(huán)22辛烷 DABCO)催化的 Baylis-Hillman反 for CsH1oN840813,1140922(10., caled for CH2NO應(yīng).催化劑 DABCO可以循環(huán)使用4次,保持產(chǎn)率高于114.0919)9%.因此,我們合成了手性氨基醇1,并在聚乙二醇1.3氨基醇1催化不對(duì)稱 Baylis-Hillman反應(yīng)(400中催化不對(duì)稱 Baylis-Hillman反應(yīng),期望既可以加般方法,以對(duì)硝基苯甲醛與丁烯酮反應(yīng)為例,向快反應(yīng)速度,又可對(duì)手性催化劑回收重復(fù)使用( Scheme045mL聚乙二醇(400中加入016g鄰硝基苯甲醛(06mmO)和014g丁烯酮(2.00mmo),攪拌下加入594mg(0.3mmo)1.室溫下攪拌,TLC跟蹤反應(yīng).反應(yīng)結(jié)束后,COoh(Boc)AcooH methyl prolinate乙醚萃取(10mL×5),合并萃取液,無(wú)水Na2SO4干燥,旋轉(zhuǎn)濃縮除去溶劑,硅膠柱層析(乙酸乙酯-石油醚)得淡黃色油狀物0.21g,產(chǎn)率954%所有不對(duì)稱 Baylis-Hillman反應(yīng)產(chǎn)物都經(jīng)過(guò)核磁譜確證為預(yù)期產(chǎn)物2結(jié)果與討論Scheme 1在這一研究工作中,我們考察了催化劑1的用量對(duì)反應(yīng)的影響,發(fā)現(xiàn)30mol%的用量比較合適,反應(yīng)可以1實(shí)驗(yàn)部分在24h內(nèi)完成,產(chǎn)率較高,選擇性與使用更多的催化劑1.1儀器和試劑相比,差別不大.在此基礎(chǔ)上,我們以30mo%的1分別在室溫和-25℃下催化一系列取代苯甲醛不對(duì)稱熔點(diǎn)用XRC1型熔點(diǎn)測(cè)定儀(四川大學(xué)科儀廠)測(cè) Baylsi-Hillman反應(yīng),結(jié)果列于表定,溫度計(jì)未校正;比旋光度用WZZ1型旋光儀(上海從表1可以看出,催化劑1對(duì)推電子基和吸電子基物理光學(xué)儀器廠)測(cè)定;核磁譜由美國(guó)Ⅴaian公司取代的底物都有一定的催化活性.對(duì)所有研究過(guò)的底Inova400型核磁共振儀記錄;元素分析由意大利cabo物,溫度對(duì)反應(yīng)速度的影響都是一致的:當(dāng)反應(yīng)溫度由Eba-110自動(dòng)元素分析儀完成;HRMS由 MicromassOA-TOF完成;ee值的測(cè)定使用 Agilent1100型高效液室溫降至-25℃時(shí),所需反應(yīng)時(shí)間延長(zhǎng),且反應(yīng)產(chǎn)率有一定程度下降.反應(yīng)溫度對(duì)反應(yīng)的立體選擇性的影響相色譜儀, Agilent100二極管陣列與多波長(zhǎng)檢測(cè)器,在則隨底物所不園對(duì)一些底物,溫度下降時(shí)反Daicel Chiralpack AS-H色譜柱上進(jìn)行,流動(dòng)相為正己烷應(yīng)選中國(guó)煤化工甲醛,也有與此相反異丙醇,據(jù)不同分析對(duì)象比例有所變化;色譜數(shù)據(jù)由的CNMHG使反應(yīng)的選擇性明顯Agilent ChemStation化學(xué)工作站釆集處理.所用試劑為提高.事實(shí)上,對(duì)氯苯甲醛和丁烯酮在30mol%1催化國(guó)產(chǎn)AR級(jí)下于-25℃在PEG(400中反應(yīng),對(duì)映體過(guò)量達(dá)到543%,是這里最好的結(jié)果( Entry91308有機(jī)化學(xué)vl.26,20061各種取代苯甲醛的不對(duì)稱 Baylis-Hillman反應(yīng)4表2催化劑1-聚乙烯醇(400體系的循環(huán)使用結(jié)果°Table 1 The asymmetric Baylis-Hillman reaction of variousTable 2 Recycling catalyst 1-PEG (400)syaldehydesYield/%ee/%(Config.95.42359(S)31.9(S)R=2-NO2, 3-NO2, 4-NO2, 2-Cl81.815.7(S)3-Cl, 4-CL, 4-0CH3, 4-BrReaction conditions: aldehyde. methyl vinyl ketone. catalyst=1.2:0.3;solvent: PEG(400); Isolated yield after column chromatography on silica gelEntry R TrC th Yield/% ee /% Config. "The ee values were determined by HPLC analyses on aDAICEL Chiralpack12NO215.9(5)OD-H column with hexane/2-propanol mixture as the eluent; "Absolute co2 2-NOfiguration was assigned by comparing the sign of the specific rotation of the3 3-NOproduct with that reported before ol.4 3-NO252463.528.1在聚乙二醇(400中催化不對(duì)稱 Baylis-Hillman反應(yīng),催95化劑溶劑體系可重復(fù)使用3次,反應(yīng)的選擇性無(wú)明顯6 4-NO252468.1143(S下降.252471.542.583-Cl252457.835.19 4-Cl47754.3(SReferences1275.5145(S1 Baylis, A. B; Hillman, M. E. D. DE 2155113, 1972 [Chem11 4-OMe1273.7Abstr.1972,7,34174]12 4+Br TL12 7156. 2 Basavaiah, D. Rao, P D. Hyma, R.S. Tetrahedron 1996Reaction conditions: aldehyde methyl vinyl ketone: catalyst=1:2:0.33 Brzezinski, L. J. Rafel, S Leahy, J. w. Tetrahedron 1997on silica gel. The ee values were determined by HPLC analyses on a DAl-aL Chiralpack AS-H, Chiralcel OJ-H, or a DAICEL Chiralpack OD-H col-53,16423.umn with hexane/2-propanol mixture as the eluent. Absolute configurations4 Mark6, I. E; Giles, P. R; Hindley, N.J. Tetrahedron 1997,were assigned by comparing the sign of the specific rotation of the product53,1015.with that reported before or.5 Iwabuchi, Y Nakatani, M: Yokoyama, N; Hatakeyama, sJ.Am.Chem.Soc.1999,12l,10219最后,我們考察了1催化的對(duì)硝基苯甲醛和丁烯酮6sShi,M;Jang,I.K., Tetrahedron: Asymmetry200.13,的反應(yīng)中催化劑1聚乙二醇(400催化劑溶劑體系循環(huán)使用的可能性(表2)7(a)Shi, M; Xu, Y.M. Shi, Y.L. Chem. Eur J. 2005, 11,從表2的數(shù)據(jù)可以看出,對(duì)催化劑1和PEG(400)1794重復(fù)使用四次,反應(yīng)的時(shí)間有一定的增長(zhǎng),反應(yīng)的產(chǎn)率(b)Shi, M; Xu, Y -M. Angew. Chem., Int. Ed. 2002, 41略有下降,前3次1的催化立體選擇性基本不變,而第48 Chandrasekhar,s; Narsihmulu,c; Saritha,B; Sultana,s次產(chǎn)物的e值有比較明顯的下降S Tetrahedron Let. 2004, 45, 5865總之,我們合成了氨基醇類有機(jī)小分子催化劑1,9 Mukaiyama, T;soa,K;Sato,T; Shimizu,H; Suzuki,K并且研究了在不同溫度下以聚乙二醇(400)為溶劑考察J.Am.Chem.Soc.1979,01,145510 Krishna, P. R; Kannan, V. Reddy, P. v N. Adv Synth了1催化的苯甲醛和取代苯甲醛的 Baylis-Hillman反應(yīng),Caal.2004,346,603產(chǎn)率最高達(dá)到954%,ee最高達(dá)543%.手性催化劑1(Y0509052 LI, L. T; DONG H. Z)中國(guó)煤化工CNMHG