CN104370976B - 含氧取代基二茂铁噁唑啉‑膦配体，其制备以及在不对称环加成反应中的应用 - Google Patents

含氧取代基二茂铁噁唑啉‑膦配体，其制备以及在不对称环加成反应中的应用 Download PDF

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CN104370976B
CN104370976B CN201410668883.3A CN201410668883A CN104370976B CN 104370976 B CN104370976 B CN 104370976B CN 201410668883 A CN201410668883 A CN 201410668883A CN 104370976 B CN104370976 B CN 104370976B
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周智明
戴力
徐迪
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Abstract

本发明涉及一种新型含氧取代基二茂铁噁唑啉‑膦配体的合成，及其在不对称环加成反应中的应用。其制备方法从(S)‑4‑甲酯‑2‑二茂铁基噁唑啉开始经历四步得到两种不同结构的含氧取代基二茂铁噁唑啉‑膦化合物。此外，将新型配体应用于一水合乙酸铜催化的不对称[3+2]1,3‑偶极环加成反应中，利用不同亲偶极体试剂可高产率和高对映选择性的合成四种不同的不对称环加成多取代吡咯烷类产物。

Description

含氧取代基二茂铁噁唑啉-膦配体，其制备以及在不对称环加 成反应中的应用
技术领域
本发明涉及一类含氧取代基的二茂铁噁唑啉-膦配体，以及不对称环加成反应，属于不对称催化及合成领域。
背景技术
不对称环加成反应在近二十年来正在快速的发展。1991年，有研究者报道了甲亚胺叶立德为反应底物的不对称[3+2]1,3-偶极环加成反应，反应中以化学计量的氯化钴或溴化锰为中心金属，麻黄碱衍生物作为不对称反应的手性配体，得到了环加成产物的对应选择性为96％ee。此后的二十几年中，以甲亚胺叶立德为底物的不对称环加成反应被陆续报道出来。到目前为止，丙烯酸酯类，烯酮类，硝基烯烃，乙烯砜类，苯醌甚至富勒烯类化合物也被用来作为亲偶极体参与到不对称[3+2]1,3-偶极环加成反应中的研究中。
亚苄基丙二酸二酯作为一种良好的Michael反应受体，常被用于不对称Michael反应中。2010年，Wang首例报道了银-(S)-TF-biphamPhos催化剂以亚苄基丙二酸二酯为亲偶极体的不对称1,3-偶极环加成反应。次年，Deng使用合成的氮,，氧-配体进行了同样的不对称1,3-偶极环加成反应。最近，Fukuzawa使用二茂铁磷，硫-配体ThioClickFerrophos进行了同样类型的不对称环加成反应。二茂铁噁唑啉-膦配体是一类在过渡金属催化不对称反应中应用十分广泛的配体。其在不对称烯丙基取代反应、不对称共轭加成反应、不对称氢化反应、不对称氢转移反应等中都取得了高产率和高对映选择性的不对称产物。但在以亚苄基丙二酸二酯作为亲偶极体的不对称1,3-偶极环加成反应却没有报道。二茂铁噁唑啉-膦配体良好的配位能力和生成催化剂的高效的立体选择性使得其在该反 应中有重要的应用价值。
发明内容
本发明的目的是为了开发一种新型的二茂铁噁唑啉-膦配体(通式I)，提供一种催化效率高的含氧取代基二茂铁噁唑啉-膦配体的合成方法。其化合物通式如下：
其中，R＝OTMS或OH。
通式(I)中化合物的合成反应如下：
本发明的另一目的是将合成的含氧取代基面手性二茂铁噁唑啉-膦配体4和5应用于不对称环加成反应中。所述反应式为：
其中，7和11：E1＝E2＝COOEt，8和12：E1＝E2＝COOEt，9和13：E1＝E2＝CN，10和14：E1＝H，E2＝NO2
在氩气保护下，将一水合醋酸铜(2.0mg,0.01mmol)和新型含氧取代基二茂铁噁唑啉-膦配体加入含分子筛的干燥Schlenk瓶后，加入5mL二氯甲烷。室温反应60分钟后，在冰水浴条件下，分别加入底物甘氨酸亚胺酯(0.25mmol)，底物烯烃(0.275mmol)和碳酸钾(3.45mg,0.025mmol)。体系在0℃反应12小时。反应结束后，蒸出溶剂，粗产品柱层析分离(硅胶100-200目，洗脱剂：石油醚:乙酸乙酯＝10:1)。exo-构型环加成产物ee值由手性液相检测。
具体实施方式
实施例1：(S)-4-(羟基二甲基)甲基-2-二茂铁基噁唑啉(2)的合成
取镁粉(335mg,14mmol)放入干燥后的三口瓶中，加入1粒碘，再加入100毫升无水乙醚，溶液呈棕黄色。冰盐浴条件下缓慢滴加碘甲烷(2.00g,14.1mmol)的无水乙醚溶液，保持体系微沸状态，形成白色悬浊液。室温反应30分钟后，在冰水浴条件下滴加(S)-4-甲酯-2-二茂铁基噁唑啉(1.01g,3.2mmol)的无水乙醚溶液，滴加过程中有沉淀析出，30分钟加毕。室温反应过夜。反应完毕后冰水浴下加入饱和氯化铵水溶液，乙酸乙酯萃取反应液，直至水层澄清为止。合并油相，无水硫酸钠干燥，蒸出溶剂，粗产品柱层析分离(硅胶100-200目，洗脱剂：石油醚:乙酸乙酯:乙醇＝10:10:1)。产物(S)-4-(羟基二甲基)甲基-2-二茂铁基噁唑啉，橙色固体，产率77％。m.p.:115-116℃。[α]D 20＝-12(c 0.25,CH2Cl2)。IR(cm-1):3152,3089,1650,1485,1356,1307,1259,1207,1125,1102,1020。 1H-NMR(400MHz,CDCl3):δ1.19(3H,s,C(CH3)(CH3)OH),1.33(3H,s,C(CH3)(CH3)OH),4.10(2H,m,Cp-H),4,20(5H,s,Cp-H),4.27(1H,br s,CHHO),4.31(1H,m,CHN),4.35(1H,br s,CHHO),4.74(1H,br s,Cp-H),4.76(1H,br s,Cp-H)。13C-NMR(400MHz,d6-DMSO):δ24.4(CH3),28.1(CH3),67.9(CHN),68.6(Cp×2),69.3(Cp×5),69.9(Cp),70.1(Cp),70.8(C(CH3)2OH),75.3(Cp),164.8 (C＝N)。MS(ESI)m/z(M+H+)314.2。
实施例2：(S)-4-(三甲基硅氧基二甲基)甲基-2-二茂铁基噁唑啉(3)的合成
将(S)-4-(羟基二甲基)甲基-2-二茂铁基噁唑啉(300mg,0.96mmol)和咪唑(326mmol,4.8mmol)溶于20毫升无水四氢呋喃中，随后加入三甲基氯硅烷(287mg,1.92mmol)，反应液立刻变浑浊。室温反应过夜后，加入大量乙醚和饱和食盐水，无水乙醚萃取反应液，直至水层无色，合并油相，无水硫酸钠干燥。蒸出溶剂，粗产品柱层析分离(硅胶100-200目，洗脱剂：石油醚:乙酸乙酯＝20:1)。产物(S)-4-(三甲基硅氧基二甲基)甲基-2-二茂铁基噁唑啉，橙色固体，产率93％。m.p.:59-60℃。IR(cm-1):3088,3071,2977,2932,2898,1649,1250,1164,1114,1017。1H-NMR(400MHz,CDCl3):δ0.11(9H,s,Si(CH3)3),1.20(3H,s,C(CH3)(CH3)OTMS),1.38(3H,s,C(CH3)(CH3)OH),4.04(2H,m,Cp-H),4.22(5H,s,Cp-H),4.25(1H,m,CHHO),4.32(1H,br s,CHN),4.39(1H,m,CHHO),4.71(1H,br s,Cp-H),4.75(1H,br s,Cp-H)。MS(ESI)m/z(M+H+)386.3。
实施例3：(S,Rp)-4-(三甲基硅氧基二甲基)甲基-2-[(2-二苯基膦)二茂铁基]噁唑啉(4)的合成
在氮气保护下，将(S)-4-(三甲基硅氧基二甲基)甲基-2-二茂铁基噁唑啉(2.80g,7.26mmol)和新蒸N,N,N,N-四甲基乙二胺(1.26g,10.9mmol)溶于50毫升无水乙醚中，得到橙色溶液。将体系降温至-78℃后，向体系滴加正丁基锂(6.8mL,1.6M,10.9mmol)，30分钟加毕。滴加完毕后，将体系缓慢恢复至0℃，反应2小时，反应体系橙色加深或变为红色。再次将体系降温至-78℃，向体系滴加二苯基氯化膦(2.42g,10.9mmol)的乙醚溶液，20分钟加毕。滴加完毕后，将体系缓慢恢复至室温，反应过夜。反应完毕，溶液中有沉淀析出；向体系中加入饱和氯化铵水溶液，后用乙酸乙酯和饱和食盐水萃取反应液，直至水层无色，合 并油相，无水硫酸钠干燥。蒸出溶剂，粗产品柱层析分离(硅胶100-200目，洗脱剂：石油醚:乙酸乙酯＝25:1)。产物(S,Rp)-4-(三甲基硅氧基二甲基)甲基-2-[(2-二苯基膦)二茂铁基]噁唑啉，黄色固体，产率87％。m.p.:107-109℃。[α]D 20＝+92.4(c 0.46,CH2Cl2)。1H NMR(500MHz,CDCl3):δ0.10(s,9H,Si(CH3)3),0.92(s,3H,CH3),1.33(s,3H,CH3),3.66(s,1H,Cp-H),3.94(t,J＝8.5Hz,1H,OCHH)4.18(m,2H,CHN+OCHH),4.20(s,5H,Cp-H),4.39(s,1H,Cp-H),5.98(s,1H,Cp-H),7.22-7.24(5H,Ph-H),7.38-7.51(5H,Ph-H)。13C NMR(125MHz,CDCl3):δ-2.55,23.40,28.78,69.02,70.77(Cp×5),72.35,73.99,75.16,76.12,78.65(d,J＝15Hz),127.85,127.98(d,J＝6.5Hz),128.13(d,J＝7.0Hz),128.88,132.42(d,J＝19Hz),132.58(d,J＝21Hz),134.84(d,J＝13Hz),139.75(d,J＝12.5Hz),165.87(C＝N)。31P NMR(242.95MHz,CDCl3):δ-19.06(s,PPh2)。MS(ESI)m/z(M+H+)570.3。
实施例4：(S,Rp)-4-(羟基二甲基)甲基-2-[(2-二苯基膦)二茂铁基]噁唑啉(5)的合成
在氮气保护下，将(S,Rp)-4-(三甲基硅氧基二甲基)甲基-2-[(2-二苯基膦)二茂铁基]噁唑啉(420mg,0.74mmol)溶于20毫升无水四氢呋喃中，体系降温至0℃后，滴加四丁基氟化铵(1.16g,3.69mmol)的无水四氢呋喃溶液，20分钟加毕。室温反应过夜后，加入大量水，并用乙酸乙酯萃取反应液，直至水层无色。合并油相，无水硫酸钠干燥，蒸出溶剂，粗产品柱层析分离(硅胶100-200目，洗脱剂：石油醚:乙酸乙酯:乙醇＝10:10:1)。产物(S,Rp)-4-(羟基二甲基)甲基-2-[(2-二苯基膦)二茂铁基]噁唑啉，橙色泡沫状固体，产率87％。m.p.:118-119℃。[α]D 20＝+227.5(c 0.40,CH2Cl2)。1H NMR(500MHz,CDCl3):δ1.12(s,3H,CH3),1,28(s,3H,CH3),3.76(s,1H,Cp-H),3.95(t,J＝9.5Hz,1H,OCHH),4.16-4.18(m, 1H,OCHH),4.20(s,5H,Cp-H),4.29(t,J＝9.0Hz,1H,CHN),4.42(s,1H,Cp-H),4.96(s,1H,Cp-H),7.23-7.28(5H,Ph-H),7.39-7.40(3H,Ph-H),7.52-7.59(2H,Ph-H)。13C NMR(125MHz,CDCl3):δ24.19,27.16,29.72,68.59,70.88(Cp×5),71.23,72.39,74.07(d,J＝5Hz),75.33,78.07(d,J＝12Hz),127.83,127.97(d,J＝6.5Hz),128.12(d,J＝7.3Hz),129.07,132.18(d,J＝18.5Hz),135.16(d,J＝21Hz),138.05(d,J＝11.5Hz),139.84(d,J＝11Hz),167.20(C＝N)。31P NMR(242.95MHz,CDCl3):δ-18.00(s,PPh2)。MS(ESI)m/z(M+H+)498.3。
实施例5：(S,Rp)-4-(三甲基硅氧基二甲基)甲基-2-[(2-二苯基膦)二茂铁基]噁唑啉(4)催化的不对称环加成反应——化合物11的合成
在氩气保护下，将一水合醋酸铜(2.0mg,0.01mmol)和(S,Rp)-4-(三甲基硅氧基二甲基)甲基-2-[(2-二苯基膦)二茂铁基]噁唑啉(6.3mg,0.011mmol)加入含分子筛的干燥Schlenk瓶后，加入5mL二氯甲烷。室温反应60分钟后，在冰水浴条件下，分别加入底物甘氨酸亚胺酯(0.25mmol)，底物亚苄基丙二酸二乙酯(0.275mmol)和碳酸钾(3.45mg,0.025mmol)。体系在0℃反应12小时。反应结束后，蒸出溶剂，粗产品柱层析分离(硅胶100-200目，洗脱剂：石油醚:乙酸乙酯＝10:1)。exo-构型环加成产物ee值由手性液相检测。
产物4,4-二乙基-2-甲基-3,5-二苯基吡咯烷-2,4,4-三酯(11)，白色固体。熔点：101-103℃；1H NMR(400MHz,CDCl3):δ7.28-7.50(m,10H,Ph-H),5.38(s,1H),4.43(d,J＝6.4Hz,1H),4.25(d,J＝7.2Hz,1H),3.78-3.83(m,5H,COOMe+CHHCH3+CHHCH3),3.45(m,1H,CHHCH3),3.37(m,1H,CHHCH3),0.81(t,J＝7.2Hz,3H,CH2CH3),0.72(t,J＝7.2Hz,3H,CH2CH3)。
产物产率98％，exo-构型对映体过量值99.2％。
实施例6：(S,Rp)-4-(羟基二甲基)甲基-2-[(2-二苯基膦)二茂铁基]噁唑啉(5)催化的不对称环加成反应——化合物10的合成
在氩气保护下，将一水合醋酸铜(2.0mg,0.01mmol)和(S,Rp)-4-(羟基二甲基)甲基-2-[(2-二苯基膦)二茂铁基]噁唑啉(5.5mg,0.011mmol)加入含分子筛的干燥Schlenk瓶后，加入5mL二氯甲烷。室温反应60分钟后，在冰水浴条件下，分别加入底物甘氨酸亚胺酯(0.25mmol)，底物亚苄基丙二酸二乙酯(0.275mmol)和碳酸钾(3.45mg,0.025mmol)。体系在0℃反应12小时。反应结束后，蒸出溶剂，粗产品柱层析分离(硅胶100-200目，洗脱剂：石油醚:乙酸乙酯＝10:1)。exo-构型环加成产物ee值由手性液相检测。
产物产率87％，exo-构型对映体过量值75.0％。
实施例7：(S,Rp)-4-(三甲基硅氧基二甲基)甲基-2-[(2-二苯基膦)二茂铁基]噁唑啉(4)催化的不对称环加成反应——化合物12的合成
在氩气保护下，将一水合醋酸铜(2.0mg,0.01mmol)和(S,Rp)-4-(三甲基硅氧基二甲基)甲基-2-[(2-二苯基膦)二茂铁基]噁唑啉(6.3mg,0.011mmol)加入含分子筛的干燥Schlenk瓶后，加入5mL二氯甲烷。室温反应60分钟后，在冰水浴条件下，分别加入底物甘氨酸亚胺酯(0.25mmol)，底物亚苄基丙二酸二甲酯(0.275mmol)和碳酸钾(3.45mg,0.025mmol)。体系在0℃反应12小时。反应结束后，蒸出溶剂，粗产品柱层析分离(硅胶100-200目，洗脱剂：石油醚:乙酸乙酯＝10:1)。exo-构型环加成产物ee值由手性液相检测。
产物2,4,4-三甲基-3,5-二苯基吡咯烷-2,4,4-三酯(12)，白色固体。1H NMR(500MHz,CDCl3):δ7.47-7.45(m,2H,Ph-H),7.35-7.27(m,8H,Ph-H),5.38(s,1H),4.43(d,J＝6.5Hz,1H),4.29(m,1H),3.79(s,3H,COOMe),3.17(s,3H,COOMe),3.14(s,3H,COOMe)。
产物产率98％，exo-构型对映体过量值95.2％。
实施例8：(S,Rp)-4-(三甲基硅氧基二甲基)甲基-2-[(2-二苯基膦)二茂铁基]噁唑啉(4)催化的不对称环加成反应——化合物13的合成
在氩气保护下，将一水合醋酸铜(2.0mg,0.01mmol)和(S,Rp)-4-(三甲基硅氧基二甲基)甲基-2-[(2-二苯基膦)二茂铁基]噁唑啉(6.3mg,0.011mmol)加入含分子筛的干燥Schlenk瓶后，加入5mL二氯甲烷。室温反应60分钟后，在冰水浴条件下，分别加入底物甘氨酸亚胺酯(0.25mmol)，底物亚苄基丙二腈(0.275mmol)和碳酸钾(3.45mg,0.025mmol)。体系在0℃反应12小时。反应结束后，蒸出溶剂，粗产品柱层析分离(硅胶100-200目，洗脱剂：石油醚:乙酸乙酯＝10:1)。exo-构型环加成产物ee值由手性液相检测。
产物4,4-二氰基-2-甲基-3,5-二苯基吡咯烷-2-酯(13)，白色固体。1H NMR(500MHz,CDCl3):δ7.69-7.67(m,2H,Ph-H),7.57-7.55(m,2H,Ph-H),7.48-7.45(m,6H,Ph-H),4.97(s,1H),4.55(d,J＝8.0Hz,1H),4.19(d,J＝8.0Hz,1H),3.74(s,3H,COOMe),2.78(br s,1H)。
产物产率95％，exo-构型对映体过量值63.0％
实施例9：(S,Rp)-4-(三甲基硅氧基二甲基)甲基-2-[(2-二苯基膦)二茂铁基]噁唑啉(4)催化的不对称环加成反应——化合物14合成
在氩气保护下，将一水合醋酸铜(2.0mg,0.01mmol)和(S,Rp)-4-(三甲基硅氧基二甲基)甲基-2-[(2-二苯基膦)二茂铁基]噁唑啉(6.3mg,0.011mmol)加入含分子筛的干燥Schlenk瓶后，加入5mL二氯甲烷。室温反应60分钟后，在冰水浴条件下，分别加入底物甘氨酸亚胺酯(0.25mmol)，底物硝基烯烃(0.275mmol)和碳酸钾(3.45mg,0.025mmol)。体系在0℃反应12小时。反应结束后，蒸出溶剂，粗产品柱层析分离(硅胶100-200目，洗脱剂：石油醚:乙酸乙酯＝10:1)。exo-构型环加成产物ee值由手性液相检测。
产物(exo)-3,5-二苯基-2-甲氧羰基-4-硝基-吡咯烷(14)。白色固体。熔点：100-102℃。1H NMR(400MHz,CDCl3):δ2.75(sb,1H),3.30(s,3H,COOMe),4.39(t,J＝8.4Hz,1H),4.51(d,J＝8.8Hz,1H),4.77(d,J＝8.0Hz,1H),5.22(t,J＝8.0Hz,1H),7.24-7.59(m,10H,Ph-H)。
产物产率99％，exo-构型对映体过量值99.0％。

Claims (3)

1.一种含氧取代基二茂铁噁唑啉-膦配体，其特征在于以下通式的化合物：
其中，R＝OTMS或OH。
2.如权利要求1所述的含氧取代基二茂铁噁唑啉-膦配体的制备方法，其特征在于：以(S)-4-甲酯-2-二茂铁基噁唑啉为起始原料，经过格氏试剂还原、羟基保护、二苯基膦基团引入、羟基脱保护四个步骤得到含氧取代基二茂铁噁唑啉-膦配体。
3.如权利要求1所述的含氧取代基二茂铁噁唑啉-膦配体在不对称环加成反应中的应用，其特征在于：在氩气保护下，将一水合乙酸铜和含氧取代基二茂铁噁唑啉-膦配体加入含分子筛的干燥Schleck瓶后，加入二氯甲烷；室温反应30分钟后，在冰水浴条件下，分别加入底物甘氨酸亚胺酯，底物烯烃和碳酸钾；体系在0℃下反应12小时；反应结束后，蒸出溶剂，粗产品使用100-200目硅胶，利用石油醚与乙酸乙酯为10：1的洗脱剂进行分离。
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1299820A (zh) * 2000-12-19 2001-06-20 中国科学院上海有机化学研究所 一种具有多种手性中心的二茂铁噁唑啉膦配体合成方法及用途
CN103772445A (zh) * 2014-02-25 2014-05-07 中国科学院上海有机化学研究所 一种1,1’-二茂铁全氟烷基膦氮配体、其制备方法及应用

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1299820A (zh) * 2000-12-19 2001-06-20 中国科学院上海有机化学研究所 一种具有多种手性中心的二茂铁噁唑啉膦配体合成方法及用途
CN103772445A (zh) * 2014-02-25 2014-05-07 中国科学院上海有机化学研究所 一种1,1’-二茂铁全氟烷基膦氮配体、其制备方法及应用

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
(S)-Serine derived N–O and N–P oxazoline ligands for asymmetric catalysis;Geraint Jones et al.;《Tetrahedron: Asymmetry》;20040519;第15卷;第654页图2 *
A Highly Enantio- and Diastereoselective Cu-Catalyzed 1,3-Dipolar Cycloaddition of Azomethine Ylides with Nitroalkenes;Xiao-Xia Yan et al.;《Angew. Chem. Int. Ed.》;20060221;第45卷;第1980页图，supporting information第2页化学式，第3页第3段 *

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