CN101486673B - 一种光学活性2-(2-硝基-乙基)-吡咯的合成方法 - Google Patents
一种光学活性2-(2-硝基-乙基)-吡咯的合成方法 Download PDFInfo
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Abstract
本发明涉及一种2-(2-硝基-乙基)-吡咯化合物、合成方法及其用途。以手性磷酸作为催化剂,由硝基烯烃和吡咯化合物可以高效率高对映选择性的合成2-(2-硝基乙基)-吡咯化合物。该方法可适用于多种不同类型的吡咯类化合物和硝基烯烃类化合物,反应条件温和,操作简便。另外,反应中无需加入任何金属盐类化合物,从而有利于药物的生产和处理。且反应的产率也较好(一般为85%-98%),对映选择性高(一般为87%-97%)。
Description
技术领域
本发明涉及一种2-(2-硝基-乙基)吡咯化合物,系由手性磷酸催化的硝基烯烃和吡咯化合物进行傅克反应高效率高对映选择性地合成2-(2-硝基-乙基)-吡咯化合物。
背景技术
近年来,有机小分子催化由于其合成容易,结构修饰方便,无重金属残留等优点在全世界范围内引起了学术界和工业界的广泛关注[(a)Seayad,J.;List,B.Org.Biomol.Chem.2005,3,719-724.(b)Dalko,P.I.;Moisan,L.Angew.Chem.Int.Ed.2004,43,5138-5175.],其中由手性磷酸作为催化剂来实现的不对称催化在近三年来更是取得了迅速的发展[(a)Q.Kang,Z.-A.Zhao,S.-L.You,J.Am.Chem.Soc.2007,129,1484-1485.(b)Q.Kang,X.-J.Zheng,S.-L.You,Chem.Eur.J.2008,14,3539-3542.(c)J.Itoh,K.Fuchibe,T.Akiyama,Angew.Chem.2008,120,4080-4082;Angew.Chem.Int.Ed.2008,47,4016-4018.(d)X.-W.Wang,C.M.Reisinger,B.List,J.Am.Chem.Soc.2008,130,6070-6071.(e)Q.-S.Guo,D.-M.Du,J.-X.Xu,Angew.Chem.Int.Ed.2008,47,759-762.],在这一领域中,我们发展了由手性磷酸催化的硝基烯烃和吡咯化合物的傅克反应,该反应可以高效率高对映选择性的合成2-(2-硝基-乙基)-吡咯化合物,而这一类化合物广泛存在于天然产物和药物中[(a) A.;Radkowski,K.;Peters,H.Angew.Chem.,Int.Ed.2005,44,2777-2781.(b)Fürstner,A.Angew.Chem.,Int.Ed.2003,42,3582-3603.(c)Johnson,J.A.;Ning,L.;Sames,D.J.Am.Chem.Soc.2002,124,6900-6903.(d)Baran,P.S.;Richter,J.M.;Lin,D.W.Angew.Chem.,Int.Ed.2005,44,609-612.(e)O’Connor,S.E.;Maresh,J.J.Nat.Prod.Rep.2006,23,532-547.]。目前文献中有效的对硝基烯烃和吡咯不对称加成反应的报道还比较少,其中几例较好的结构都使用了金属络合物催化剂[(a)B.M.Trost,C.Müller,J.Am.Chem.Soc.2008,130, 2438.(b)H.Liu,S.-F.Lu,J.Xu,D.-M.Du,Chem.Asian J.2008,3,1111]。因而发展一种操作方便,环境友好,而且高效率高对映选择性的合成2-(2-硝基-乙基)-吡咯化合物的方法是这方面的重点和难点。本发明人发展的利用手性磷酸这一有机小分子催化剂,在数分钟到数小时内催化这一反应,对合成此类化合物有着重要的意义。
发明内容
本发明的目的是提供一种2-(2-硝基-乙基)-吡咯化合物;
本发明的目的或提供一种有效的合成上述2-(2-硝基-乙基)-吡咯化合物的方法;
本发明的2-(2-硝基-乙基)-吡咯化合物,具有如下结构式:
其中:R1任意选自H、Ac、Boc、Bz、Fmoc、Troc或C1_C16的烷基;R3、R4或R5任意选自H、F、Cl、Br、I、C1_C16的烃氧基、C1_C16的烷基、C2_C16烯基、C2_C16炔基、C3_C16环烷基、苄基或氨基;R6、R7或R8任意选自H、C1_C16的烷基、杂芳环、 取代的芳基,其中R9、R10、R11、R12或R13任意选自H、F、Cl、Br、I、C1_C16的烃氧基、C1_C16的烷基、C2_C16烯基、C2_C16炔基、C3_C16环烷基、苄基、氨基或共轭芳基;其中;所述的共轭芳基为萘基、蒽基或菲基;所述的芳基为苯基或萘基;所述的杂环基为C5~C10的含N,O,S的杂环基;Ac代表乙酰基、Boc代表叔丁氧羰基、 Bz代表苯甲酰基、Fmoc代表芴甲氧羰基、Troc代表2,2,2-三氯乙氧羰基。
本发明的2-(2-硝基-乙基)-吡咯化合物是以硝基烯烃和吡咯化合物为原料,在有机溶剂的存在下,以手性磷酸为催化剂反应制得,可用如下反应式表示:
该反应的进一步的描述是在有机溶剂中和温度为-78℃至100℃,硝基烯烃和吡咯化合物为原料,以手性磷酸为催化剂反应3分钟-48小时;所述的硝基烯烃、吡咯化合物、手性磷酸的摩尔比为1∶1-10∶0.0001-1,推荐反应的摩尔比为:硝基烯烃∶吡咯化合物∶手性磷酸=1∶1-4∶0.001-0.1。推荐反应温度为:-50℃至30℃。
吡咯化合物的结构式为: 其中:R1任意选自H、Ac、Boc、Bz、Fmoc、Troc、C1_C16的烷基;R2为H;R3,R4或R5,任意选自H、F、Cl、Br、I、C1_C16的烃氧基、C1_C16的烷基、C2_C16的烯基、C2_C16的炔基、C3_C16的环烷基、苄基、氨基;硝基烯烃的结构式为: R6、R7、R8任意选自H、C1_C16的烷基、杂芳环、 取代的芳基;其中R9、R10、R11、R12或R13任意选自H、F、Cl、Br、I、C1_C16的烃氧基、C1_C16的烷基、C2_C16的烯基、C2_C16的炔基、C3_C16的环烷基、苄基或氨基,也可以为共轭芳基;所述的Ac、Boc、Bz、Fmoc、Troc和共轭芳基如前所述。
催化剂的结构通式为(为任意光学纯的结构,不受图示所限):
本发明中所提到的烷基,烃氧基等,除非另外说明,均推荐碳数为1~16的基团,进一步推荐碳数为1~10的,尤其推荐碳数为1~4的。烯基、炔基的碳数为2~16的基团、进一步推荐碳数为2~10的,尤其推荐碳数为1~4的。本发明中所提到的环烷基,除非另外说明,均指碳数为3~16的基团,进一步推荐碳数为3~10的,尤其推荐碳数为3~7的。本发明中所提到的芳基,除非另外说明,均指苯基或萘基,推荐为苯基。所述的杂环基为C5~C10的含N,O,S的杂环基。
本发明方法中,所述水为蒸馏水。所述有机溶剂可以是极性或非极性溶剂。如苯、四氯化碳、石油醚、四氢呋喃、二甲基甲酰胺、乙醚、二氯甲烷、三氯甲烷、甲苯、二甲苯、环己烷、正己烷、正庚烷、二烷六环、乙腈等。
采用本发明方法所得产物可以经过重结晶,薄层层析,柱层析,减压蒸馏等方法加以分离。例如用薄层层析和柱层析方法,所用的展开剂为极性溶剂与非极性溶剂的混合溶剂。推荐溶剂可为异丙醇——石油醚,乙酸乙酯——石油醚,乙酸乙酯——正己烷,异丙醇——乙酸乙酯——石油醚,二氯甲烷——石油醚等混合溶剂,其体积比可以分别是:极性溶剂∶非极性溶剂=1∶0.1-500。例如:乙酸乙酯∶石油醚=1∶0.1-50,异丙醇∶石油醚=1∶0.1-500。
本发明提供了一种有效的由手性磷酸作为催化剂,由硝基烯烃和吡咯化合物高效率高对映选择性的合成2-(2-硝基-乙基)-吡咯化合物的方法。该合成方法催化剂相对易得、催化活性高、底物适用范围广、产物对映选择性高,可适用于多种不同类型的吡咯类化合物和硝基烯烃类化合物,反应条件温和,操作简便。另外,反应中无需加入任何金属盐类化合物,从而有利于药物的生产和处理。且反应的产率也较好(一般为85%-98%),对映选择性高(一般为87%-97%)。
具体实施方式
通过下述实施例将有助于理解本发明,但并不限制本发明的内容。
实施例1:手性磷酸的制备
室温氩气保护下,在一干燥的反应管中将BINOL的衍生物(0.5mmol)溶于1mL干燥的吡啶中,在快速搅拌的条件下,将(1.0mmol)的三氯氧磷缓慢的滴加到体系中,室温搅拌3个小时。1mL水缓慢的滴加到体系中,再在室温搅拌30分钟。加入二氯甲烷溶解,用1N盐酸水溶液(10mL×3)洗涤,有机层用无水硫酸钠干燥,减压旋去溶剂,残留物柱层析分离得产物。
(S)-3,3′-[3,5-二(三氟甲基)苯基]2-1,1′-联二萘酚磷酸
(S)-3,3′-[3,5-Bis(trifluoromethyl)phenyl]2-1,1′-binaphthyl phosphate
固体,89%产率(yield)。IR(压膜法)1620,1501,1474,1379,1325,1281,1246,1178,1140,1109,1084,1024,988,964,891,870,867cm-1.1H NMR(400MHz,CDCl3)δ=8.01(s,8H),7.61-7.58(m,4H),7.42-7.39(m,4H).31P NMR(189MHz,CDCl3)δ=4.61.13C NMR(100MHz,CDCl3)δ=143.5(d,JP-C=9.3Hz),138.6,132.3,132.0,131.4,131.4(q,JC-F=33.4Hz),131.1(d,JP-C=3.1Hz),129.9,128.7,127.6,127.1,126.8,123.1(q,JC-F=272.9Hz),122.5(d,JP-C=1.9Hz),121.5.19F NMR(376MHz,CDCl3)δ=96.3.
实施例2:手性磷酸催化的吡咯类化合物对硝基烯烃的加成反应
在一干燥的反应管中依次加入(手性)磷酸化合物(0.0015mmol),吡咯类化合物(0.45mmol),苯/二氯甲烷0.6mL及 分子筛(50-100mg),在常温搅拌下,慢慢滴加硝基烯烃化合物(0.30mmol)(溶于0.6mL苯/二氯甲烷)2小时滴完,柱层析分离得产物。
P1:2-(2-硝基-1-苯乙基)-吡咯
P1:2-(2-nitro-1-phenylethyl)-1H-pyrrole
Rf=0.40(二氯甲烷/石油醚=1/1,v/v);褐色固体;94%yield,89%ee;1H NMR(400MHz,CDCl3)δ4.78(dd,J=11.9Hz,7.6Hz,1H),4.86-4.89(m,1H),4.96(dd,J=11.9Hz,7.3Hz,1H),6.06-6.08(m,1H),6.14-6.17(m,1H),6.65-6.67(m,1H),7.20-7.24(m,2H),7.27-7.36(m,3H),7.82(br,1H);13C NMR(100MHz,CDCl3)δ42.9,79.2,105.8,108.6,118.2,127.9(2C),128.1,128.9,129.2(2C),137.9;IR(压膜法)3426,3030,2917,2360,1958,1890,1814,1552,1430,1378,1196,1120,1097,1032,725cm-1;高分辨质谱计算值: (C12H12N2O2)m/z 215.0821实测值:m/z 215.0824;手性测试条件:OD-H(25cm),正己烷/异丙醇=80/20,1.0mL/min-1,λ=254nm,t(major)=13.61min,t(minor)=16.36min.
P2:2-(2-硝基-1-对甲苯基乙基)-吡咯
P2:2-(2-nitro-1-p-tolylethyl)-1H-pyrrole
Rf=0.40(二氯甲烷/石油醚=1/1,v/v);褐色固体;91%yield,90%ee;1H NMR(400MHz,CDCl3)δ2.34(s,3H),4.78(dd,J=11.2Hz,7.7Hz,1H),4.84-4.89(m,1H),4.98(dd,J=11.2Hz,6.5Hz,1H),6.08(s,1H),6.15-6.18(m,1H),6.67-6.69(m,1H),7.10-7.18(m,4H),7.83(br,1H);13C NMR(100MHz,CDCl3)δ21.0,42.5,79.3,105.6,108.6,118.0,127.8,129.1(2C),129.8(2C),134.8,137.9;IR(压膜法)3388,2919,1546,1513,1430,1378,1195,1123,1034cm-1;高分辨质谱计算值:(C13H14N2O3)m/z 230.1055.实测值:m/z 230.1058;手性测试条件:OC-H(25cm),正己烷/异丙醇=95/5,0.8mL/min-1,λ=254nm,t(major)=51.71min,t(minor)=54.67min.
P3:2-(1-(2-甲氧基苯基)-2-硝基乙基)-吡咯
P3:2-(1-(2-methoxyphenyl)-2-nitroethyl)-1H-pyrrole
Rf=0.40(二氯甲烷/石油醚=1/1,v/v);黄色液体;90%yield,83%ee;1H NMR(400MHz,CDCl3)δ3.89(s,3H),4.89(dd,J=10.8Hz,6.5Hz,1H),4.94(dd,J=10.8Hz,5.0Hz,1H),5.18-5.22(m,1H),6.07-6.09(m,1H),6.11-6.13(m,1H),6.65-6.66(m,1H),6.88-6.93(m,2H),7.03-7.05(m,1H),7.23-7.27(m,1H),8.25(br,1H);13C NMR(100MHz,CDCl3)δ38.1,55.6,77.7,106.0,108.4,111.2,121.3,126.3,129.0,129.1,129.2,156.6;IR(压膜法)3430,2941,2361,1600,1552,1493,1378,1245,1122,1028,912,800,726cm-1;高分辨质谱计算值:(C13H14N2O3)m/z 246.1004.实测值:m/z 246.1003;手性测试条件:AD-H(25cm),正己烷/异丙醇=95/5,1.0mL/min-1,λ=254nm,t(major)=18.76min,t(minor)=22.47min.
P4:2-(1-(3-溴苯基)-2-硝基乙基)-吡咯
P4:2-(1-(3-bromophenyl)-2-nitroethyl)-1H-pyrrole
Rf=0.40(二氯甲烷/石油醚=1/1,v/v);黄色固体;91%yield,85%ee;1H NMR(400MHz,CDCl3)δ4.74-4.80(m,1H),4.82-4.87(m,1H),4.92-4.98(m,1H),6.06-6.08(m,1H),6.15-6.18(m,1H),6.68-6.71(m,1H),7.14-7.25(m,2H),7.36-7.44(m,2H),7.90(br,1H);13C NMR(100MHz,CDCl3)δ42.4,78.8,106.0,108.8,118.5,123.1,126.5,128.0,130.7,130.9,131.3,140.3;IR(压膜法)3433,2918,1552,1474,1430,1377,1195,1098,1074,1034,998,883,790,726cm-1;高分辨质谱计算值:(C12H11BrN2O2)m/z 294.0004.实测值:m/z 294.0007;手性测试条件:OD-H(25cm),正己烷/异丙醇=90/10,0.8mL/min-1,λ=254nm,t(major)=34.57min,t(minor)=47.81min.
P5:2-((1-环己基)-2-硝基乙基)-吡咯
P5:2-(1-cyclohexyl-2-nitroethyl)-1H-pyrrole
Rf=0.40(二氯甲烷/石油醚=1/1,v/v);黄色固体;96%yield,80%ee;1H NMR(400 MHz,CDCl3)δ0.90-1.31(m,5H),1.54-1.78(m,6H),3.34(dt,J=9.2Hz,6.3Hz,1H),4.58(dd,J=12.6Hz,9.2Hz,1H),4.69(dd,J=12.6Hz,5.9Hz,1H),5.95-5.97(m,1H),6.14-6.16(m,1H),6.67-6.68(m,1H),8.05(br,1H);13C NMR(100MHz,CDCl3)δ26.0(2C),26.1,30.0,31.1,40.6,43.5,78.1,106.0,108.6,117.0,128.9;IR(压膜法)3418,2928,2854,1556,1450,1380,1272,1199,1098,1030,912,793,721cm-1;高分辨质谱计算值:(C12H18N2O2)m/z 222.1368.实测值:m/z 222.1370;手性测试条件:OD-H(25cm),正己烷/异丙醇=95/5,1.0mL/min-1,λ=254nm,t(major)=20.70min,t(minor)=22.50min.
P6:2-(1-(硝基甲基)-丁基)-吡咯
P6:2-(1-(nitromethyl)butyl)-1H-pyrrole
Rf=0.40(二氯甲烷/石油醚=1/1,v/v);无色液体;90%yield,85% ee;1H NMR(400MHz,CDCl3)δ0.91(t,J=7.3Hz,3H),1.24-1.42(m,2H),1.59-1.74(m,2H),3.49-3.57(m,1H),4.49(dd,J=11.5Hz,6.8Hz,1H),4.54(dd,J=11.5Hz,5.9Hz,1H),6.00-6.02(m,1H),6.15-6.17(m,1H),6.68-6.70(m,1H),8.15(br,1H);13C NMR(100MHz,CDCl3)δ13.7,20.1,34.4,37.2,80.4,105.3,108.6,117.3,129.9;IR(压膜法)3418,2961,2874,1552,1467,1430,1381,1197,1126,1031,796,722cm-1;高分辨质谱计算值:(C9H14N2O2)m/z 182.1055.实测值:m/z182.1056;手性测试条件:OD-H(25cm),正己烷/异丙醇=98/2,0.8mL/min-1,λ=254nm,t(major)=43.19min,t(minor)=46.08min.
P7:2-(2-甲基-1-(硝基甲基)丙基)-吡咯
P7:2-(3-methyl-1-nitrobutan-2-yl)-1H-pyrrole
Rf=0.40(二氯甲烷/石油醚=1/1,v/v);无色液体;91%yield,81%ee;1H NMR(400MHz,CDCl3)δ0.90(d,J=6.7Hz,3H),0.97(d,J=6.7Hz,3H),1.89-2.02(m,1H),3.35(dt,J=9.1Hz,6.3Hz,1H),4.59(dd,J=12.7Hz,9.1Hz,1H),4.67(dd,J=12.6Hz,6.1Hz,1H),5.97-5.99(m,1H),6.15-6.17(m,1H),6.67-6.69(m,1H),8.07(br,1H);13C NMR(100MHz,CDCl3)δ19.4,20.6,30.8,44.1,78.3,106.0,108.5,117.0,128.5;IR(压膜法)3419,2964,1552,1470,1433,1381,1200,1097,1032,793,721cm-1;高分辨质谱计算值:(C9H14N2O2)m/z 182.1055.实测值:m/z 182.1056;手性测试条件:OJ-H(25cm),正己烷/异丙醇=90/10,1.0mL/min-1,λ=254nm,t(major)=17.57min,t(minor)=19.61min.
P8:2-(2-硝基-1-(2-噻吩基)乙基)-吡咯
P8:2-(2-nitro-1-(thiophen-2-yl)ethyl)-1H-pyrrole
Rf=0.40(二氯甲烷/石油醚=1/1,v/v);褐色液体;95%yield,92%ee;1H NMR(400MHz,CDCl3)δ4.81(dd,J=12.9Hz,8.0Hz,1H),4.91(dd,J=12.9Hz,7.5 Hz,1H),5.18(t,J=7.8Hz,1H),6.08-6.10(m,1H),6.15-6.17(m,1H),6.68(td,J=2.7Hz,1.5Hz,1H),6.92(ddd,J=3.5Hz,1.3Hz,0.8Hz,1H),6.95(dd,J=5.1Hz,3.5Hz,1H),7.23(dd,J=5.1Hz,1.3Hz,1H),8.03(br,1H);13C NMR(100MHz,CDCl3)δ38.1,79.6,105.9,108.8, 118.2,125.5,125.8,127.2,128.3,141.0;IR(压膜法)3426,3110,2977,2360,1556,1427,1376,1243,1196,1096,1032,911,797,729cm-1;高分辨质谱计算值:(C10H10N2O2S)m/z 222.0463.实测值:m/z 222.0466;手性测试条件:AD-H(25cm),正己烷/异丙醇=90/10,1.0mL/min-1,λ=254nm,t(major)=13.02min,t(minor)=14.82min.
P9:2-(1-(2-呋喃基)-2-硝基乙基)-吡咯
P9:2-(1-(furan-2-yl)-2-nitroethyl)-1H-pyrrole
Rf=0.40(二氯甲烷/石油醚=1/1,v/v);黄色液体;97%yield,93%ee;1H NMR(300MHz,CDCl3)δ4.81(m,1H),4.90(dd,J=12.7Hz,7.7Hz,1H),5.03(t,J=7.6Hz,1H),6.11-6.12(m,1H),6.16-6.21(m,2H),6.34-6.36(m,1H),6.72-6.75(m,1H),7.41-7.42(m,1H),8.28(brs,1H);13C NMR(75MHz,CDCl3)δ36.9,77.7,106.6,107.9,108.7,110.7,118.3,126.1,142.5,150.6;IR(压膜法)3410,3026,2917,2831,1558,1506,1457,1429,1377,1223,1143,1013,917,743,668,414cm-1;高分辨质谱计算值:(C10H10N2O3)m/z 206.0691.实测值:m/z 206.0695;手性测试条件:AD-H(25cm),正己烷/异丙醇=90/10,1.0mL/min-1,λ=254nm,t(major)=11.82min,t(minor)=12.87min.
P10:3-硝基-2-吡咯基-丙酸乙酯
P10:Ethyl 3-nitro-2-(1H-pyrrol-2-yl)propanoate
Rf=0.40(二氯甲烷/石油醚=1/1,v/v);黄色液体;89%yield,86%ee;1H NMR(400MHz,CDCl3)δ1.28(t,J=7.1Hz,3H),4.17-4.35(m,2H),4.49(dd,J=9.6Hz,5.0Hz,1H),4.68(dd,J=14.6Hz,5.0Hz,1H),5.03(dd,J=14.6Hz,9.6Hz,1H),6.06-6.07(m,1H),6.15-6.17(m,1H),6.77-6.78(m,1H),8.54(br,1H);13C NMR(100MHz,CDCl3)δ13.8,42.3,62.3,74.7,107.5,109.0,119.0,122.1,170.0;IR(压膜法)3402,2984,1732,1556,1418,1378,1246,1185,1096,1033,802,731cm-1;高分辨质谱计算 值:(C9H12N2O4)m/z 212.0797.实测值:m/z 212.0801;手性测试条件:AD-H(25cm),正己烷/异丙醇=90/10,1.0mL/min-1,λ=254nm,t(major)=10.80min,t(minor)=13.88 min.
P11:4-(5-(1-(呋喃基)-2-硝基乙基)-吡咯基)-2-丁酮
P11:4-(5-(1-(furan-2-yl)-2-nitroethyl)-1H-pyrrol-2-yl)butan-2-one
Rf=0.40(二氯甲烷/石油醚=1/1,v/v);黄色液体;94%yield,92%ee;1H NMR(400MHz,CDCl3)δ2.14(s,3H),2.73-2.80(m,4H),4.76(dd,J=12.46Hz,7.35Hz,1H),4.86(dd,J=12.45Hz,7.90Hz,1H)4.93(t,J=7.62Hz,1H),5.77-5.78(m,1H),5.90-5.91(m,1H),6.16-6.17(m,1H),6.31-6.32m,1H),7.38-7.39(m,1H),8.56(br,1H);13C NMR(100MHz,CDCl3)δ21.3,29.9,37.0,43.7,77.7,105.7,106.2,107.5,110.4,125.1,132.0,142.5,150.9,209.5;IR(压膜法)3379,2922,2253,1715,1556,1428,1373,1167,1456,1047,1012,915cm-1;高分辨质谱计算值:(C14H16N2O4)m/z 276.1110.实测值:m/z 276.1114;手性测试条件:AD-H(25cm),正己烷/异丙醇=90/10,0.8mL/min-1,λ=254nm,t(major)=18.19min,t(minor)=45.59min.
P12:3-(5-(1-(呋喃基)-2硝基乙基)-吡咯基)-1-苯丙酮
P12:3-(5-(1-(furan-2-yl)-2-nitroethyl)-1H-pyrrol-2-yl)-1-phenylpropan-1-one
Rf=0.40(二氯甲烷/石油醚=1/1,v/v);黄色固体;93%yield,85%ee;1H NMR(400MHz,CDCl3)δ2.96-2.99(m,2H),3.27-3.30(m,2H),4.76(t,3 J=12.6Hz,7.2Hz,1H),4.86(dd,J=12.6Hz,8.1Hz.,1H),4.94(t,J=7.7Hz,1H),5.84(t,J=3.0Hz,1H),5.91(t,J=3.0Hz,1H),6.15-6.16(m,1H),6.29-6.30(m,1H),7.37-7.38(m,1H),7.42-7.47(m,2H),7.54-7.58(m,1H),7.92-7.95(m,2H),8.65(br,1H);13C NMR(100MHz,CDCl3)δ21.5,37.1,39.0,77.7,105.8,106.2,107.5,110.4,125.0,128.1(2C),128.6(2C),132.2,133.3,136.6,142.6,150.9,200.5;IR(压膜法)3394,2919,1682,1552,1505,1449,1376,1205, 1014,917,742,690cm-1;高分辨质谱计算值:(C19H18N2O4)m/z 338.1267.实测值:m/z 338.1270;手性测试条件:AS-H(25cm),正己烷/异丙醇=70/30,1.0mL/min-1,λ=254nm,t(major)=21.26min,t(minor)=25.54min.
P13:1-甲基-2-(2-硝基1-苯乙基)-吡咯
P13:1-methyl-2-(2-nitro-1-phenylethyl)-1H-pyrrole
P14:1-叔丁氧酰基-2-(2-硝基-1-苯基乙基)-吡咯
P14:tert-butyl 2-(2-nitro-1-phenylethyl)-1H-pyrrole-1-carboxylate
Rf=0.40(二氯甲烷/石油醚=1/1,v/v);黄色固体;93%yield,89%ee;高分辨质谱计算值:(C17H20N2O4)m/z 316.1423.实测值:m/z316.1425.
P15:1-苯基-2-(2-硝基-1-苯基乙基)-吡咯
P15:1-benzyl-2-(2-nitro-1-phenylethyl)-1H-pyrrole
P16:1-叔丁基二甲基硅基-2-(2-硝基-1-苯基乙基)-吡咯
P16:1-(tert-butyldimethylsilyl)-2-(2-nitro-1-phenylethyl)-1H-pyrrole
Rf=0.40(二氯甲烷/石油醚=1/1,v/v);黄色固体;90%yield,90% ee;高分辨质谱计算值:(C18H26N2O2Si)m/z 330.1764.实测值:m/z 330.1766.
P17:1-烯丙基-2-(2-硝基-1-苯基乙基)-吡咯
P17:1-allyl-2-(2-nitro-1-phenylethyl)-1H-pyrrole
Rf=0.40(二氯甲烷/石油醚=1/1,v/v);黄色固体;91%yield,89%ee;高分辨质谱计算值:(C15H16N2O2)m/z 256.1212.实测值:m/z256.1213.
P18:2-(1-环己基-2-硝基乙基)-1-甲基-吡咯
P18:2-(1-cyclohexyl-2-nitroethyl)-1-methyl-1H-pyrrole
实施例3:2-(2-硝基乙基)-吡咯化合物的转化
在一蛋型瓶中,2-(2-硝基乙基)-吡咯化合物(1mmol)溶解于乙腈(7mL),在常温下加入NaIO4水溶液(0.06mmol/21mL),加完搅拌15分钟。加入三氯化钌化合物搅拌2小时,反应结束用乙酸乙酯萃取(3x10mL)。有机层合并加入乙醚(15mL)后搅拌几分钟。加入无水硫酸镁干燥,减压除去溶剂后残留物柱层析分离得粗产物。将之溶解于四氢呋喃(0.5mL)中,在零度下加入草酰氯(0.3mmol),加完后于常温搅拌1小时,将溶剂和多余的草酰氯减压除去。将所得粗产物溶于乙醇中并在常温搅拌20分钟,减压除去溶剂后残留物柱层析分离得产物。
P19:3-硝基-2苯基-丙酸甲酯
P19:Methyl 3-nitro-2-phenylpropanoate
Rf=0.40(二氯甲烷/石油醚=1/1,v/v);黄色液体;25%yield,89%ee;1H NMR(400MHz,CDCl3)δ3.74(s,3H),4.45(dd,J=10.0Hz,5.1Hz,1H),4.55(dd,J=14.7Hz,5.2Hz,1H),5.11(dd,J=14.7Hz,10.0Hz,1H),7.27-7.28(m,2H),7.35-7.40(m,3H);13C NMR(75MHz,CDCl3)δ48.6,52.8,75.7,127.8,128.7,129.3,133.2,171.0高分辨质谱计算值:(C10H11N2O4)m/z 209.0688.实测值:m/z 209.0690;手性测试条件:OD-H(25cm),正己烷/异丙醇=90/10,1.0mL/min-1,λ=254nm,t(major)=30.62min,t(minor)=14.34min.
Claims (3)
1.一种合成2-(2-硝基乙基)-吡咯化合物的方法,其特征是在-78℃至100℃和有机溶剂中,以硝基烯烃和吡咯化合物为原料,以手性磷酸为催化剂进行傅克反应3分钟-48小时,所述的硝基烯烃、吡咯化合物和手性磷酸的摩尔比为1∶1-10∶0.001-1;其中,所述的2-(2-硝基乙基)-吡咯化合物的结构式如下: 所述的硝基烯烃结构式如下: 吡咯化合物的结构式如下: 所述的催化剂的结构式为 其中,R1任意选自H、Ac、Boc、Bz、Fmoc、Troc或C1-C16的烷基;R2为H;R3、R4或R5任意选自H、F、C1、Br、I、C1-C16的烃氧基、C1-C16的烷基或C3-C16环烷基;R6、R7任意选自H、C1-C16的烷基或取代的芳基 R8选自H;R14、R15、R16、R17或R18任意选自H、C1-C16的烷基、三(C1-C16烷基)硅基或三芳基硅基、取代的芳基 或共轭芳基;其中R9、R10、R11、R12或R13任意选自H、F、Cl、Br、I、C1-C16的烃氧基、C1-C16的烷基、C2-C16烯基、C2-C16炔基、C3-C16环烷基、苄基、氨基或共轭芳基;所述的共轭芳基为萘基、蒽基或菲基;所述的芳基为苯基或萘基;Ac代表乙酰基、Boc代表叔丁氧羰基、Bz代表苯甲酰基、Fmoc代表芴甲氧羰基、Troc代表2,2,2-三氯乙氧羰基。
2.如权利要求1所述的合成2-(2-硝基乙基)-吡咯化合物的方法,其特征是所述有机溶剂是苯、四氯化碳、石油醚、四氢呋喃、二甲基甲酰胺、乙醚、二氯甲烷、三氯甲烷、甲苯、二甲苯、环己烷、正己烷、正庚烷、二氧六环或乙腈。
3.如权利要求1所述的合成2-(2-硝基-乙基)-吡咯化合物的方法,其特征是所得产物经过重结晶、薄层层析、柱层析或减压蒸馏加以分离。
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---|
Barry M. Trost et al."Asymmetric Friedel-Crafts Alkylation of Pyrroles with Nitroalkenes Using a Dinuclear Zinc Catalyst".《Journal of the American Chemistry》.2008,第130卷2438-2439,S2-12. |
Barry M. Trost et al."Asymmetric Friedel-Crafts Alkylation of Pyrroles with Nitroalkenes Using a Dinuclear Zinc Catalyst".《Journal of the American Chemistry》.2008,第130卷2438-2439,S2-12. * |
Chunchi Lin et al."I2-catalyzed Michael addition of indole and pyrrole to nitroolefins".《Tetrahedron》.2005,第61卷(第49期),11751-11757. |
Qiang Kang et al."Highly Enantioselective Friedel-Crafts Reaction of Indoles with Imines by a Chiral Phosphoric Acid".《Journal of the American Chemistry》.2007,第129卷(第6期),1484-1485. |
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