含咪唑盐基团的二茂铁膦亚胺配体、其制备以及在催化不对称烯丙基取代反应中的应用转让专利
申请号 : CN200810167172.2
文献号 : CN101712697B
文献日 : 2011-09-07
发明人 : 周智明 , 袁浩
申请人 : 北京理工大学
摘要 :
权利要求 :
1.一种含咪唑盐基团的二茂铁膦亚胺配体,其特征在于为以下通式化合物:
其中二茂铁骨架的手性分别为(R,Sp),(S,Rp)。
2.如权利要求1所述的一种含咪唑盐基团的二茂铁膦亚胺配体的制备方法,其特征在于:将1-(2-二苯基膦)二茂铁乙胺、芳香醛咪唑盐溶解到二氯甲烷中,加入脱水剂无水硫酸钠,室温下搅拌,将无水硫酸钠过滤,母液浓缩得到黄色固体,用有机溶剂洗涤、干燥,得到含咪唑盐基团的二茂铁膦亚胺配体。
3.如权利要求2所述的一种含咪唑盐基团的二茂铁膦亚胺配体的制备方法,其特征在于:搅拌时间为1~8小时。
4.如权利要求2或3所述的一种含咪唑盐基团的二茂铁膦亚胺配体的制备方法,其特征在于:洗涤的有机溶剂为无水乙醚、乙酸乙酯、石油醚、苯或甲苯。
5.如权利要求1所述的一种含咪唑盐基团的二茂铁膦亚胺配体在不对称烯丙基取代反应的应用,其特征在于:含咪唑盐基团的二茂铁膦亚胺配体催化不对称烯丙基取代反应的步骤是将烯丙基氯化钯二聚体[Pd(η-C3H5)Cl]2和手性配体溶解到二氯甲烷中,氩气保护下室温反应0.5~2小时,往该溶液中依次加入1,3-二苯基-2-烯丙基-1-醇的乙酸酯、丙二酸二甲酯、N,O-二(三甲基硅)乙酰胺(BSA)和无水醋酸钾,密闭反应12~36小时,加入饱和氯化铵溶液结束反应,萃取、干燥、浓缩、纯化得到取代产品。
6.如权利要求5所述的含咪唑盐基团的二茂铁膦亚胺配体在不对称烯丙基取代反应的应用,其特征在于:所述手性配体的用量为烯丙基氯化钯二聚体[Pd(η-C3H5)Cl]2的2~
3倍摩尔比;所述手性配体用量为1,3-二苯基-2-烯丙基-1-醇的乙酸酯的1%~5%摩尔百分数;所述1,3-二苯基-2-烯丙基-1-醇的乙酸酯、丙二酸二甲酯、N,O-二(三甲基硅)乙酰胺(BSA)和无水醋酸钾的摩尔比为1∶2~4∶2~4∶0.01~0.02;所述溶剂用量为每毫摩尔1,3-二苯基-2-烯丙基-1-醇的乙酸酯使用8~10ml二氯甲烷。
说明书 :
含咪唑盐基团的二茂铁膦亚胺配体、其制备以及在催化不
对称烯丙基取代反应中的应用
技术领域
发明内容
具体实施方式
96%。将1-甲基-3-(4-醛基-卞基)-1H-咪唑溴盐(1.405g,5mmol)溶解到20ml蒸馏水中,滴加六氟磷酸铵(1.104g,6mmol)水溶液,室温反应3h,有白色固体析出,过滤,蒸馏水充分洗涤固体,产品真空干燥,得到1-甲基-3-(4-醛基-卞基)-1H-咪唑六氟磷酸盐,产率
1
97%。m.p.=108~110℃。H-NMR(300MHz,DMSO4-d6):δ3.874(s,3H,CH3),5.574(s,2H,CH2),7.613(d,2H,J=7.8Hz,Ph-H),7.766(s,1H,imidazoleH),7.837(s,1H,imidazoleH),+
7.963(d,2H,J=7.8Hz,Ph-H),9.299(s,1H,NCHN),10.032(s,1H,CHO)。ESI:m:z=201M,-
m:z=145M。
率91%。m.p.=194~196℃。[α]D =-342.70(c=0.6,CH2Cl2)。H-NMR(300MHz,DMSO4-d6):δ1.608(d,3H,J=6.6Hz,CHCH3),3.917(s,3H,CH3),4.081(s,5H,unsubstrated Cp-H),3.774-4.702(m,3H,substrated Cp-H),4.825(m,1H,CHMe),5.423(s,2H,CH2),
6.820~7.779(m,16H,imidazoleH and Ph-H),8.104(s,1H,N=CH),9.226(s,1H,NCHN)。
31 13
P-NMR(200MHz,DMSO4-d6):δ-24.498(s,1P,PPh2);-143.685(m,1P,PF6)。C-NMR(400MHz,DMSO4-d6):δ22.309(CHMe),39.796(NMe),52.148(Ph-CH2-N),63.945(CHMe),69.644,
69.650,71.690,75.447,122.754,124.579,127.658,128.126,128.394,128.709.129.684,+
132.302,135.436,136.721,137.219,137.687,139.753,158.911.ESIm:z= 596M,m:z =-
145M。Anal.Calc.for C36H35F6FeN3OP2:C,58.31;H,4.76;N,5.67.Found:C,57.79;H,
4.80;N,5.66.
同上,产率93%。[α]D =+342.60(c=0.6,CH2Cl2)。
1
97%。m.p.=128~130℃。H-NMR(300MHz,DMSO4-d6):δ3.835(s,3H,CH3),5.345(s,2H,CH2),7.043(d,1H,J=8.7Hz,Ph-H),7.590(d,1H,J=7.8Hz,Ph-H),7.612(s,1H,Ph-H),
7.689(s,1H,imidazoleH),7.764(s,1H,imidazoleH),9.146(s,1H,NCHN),10.291(s,1H,+ -
CHO),10.955(s,1H,OH)。ESI:m:z=217M,m:z=145M。
涤得到产品。产率94%。m.p.=151~153℃。[α]D =-309.25。H-NMR(300MHz,DMSO4-d6):δ1.615(d,3H,J=6.6Hz,CHCH3),3.863(s,3H,CH3),4.081(s,5H,unsubstrated Cp-H),3.756-4.695(m,3H,substratedCp-H),4.772(m,1H,CHMe),5.219(s,2H,CH2),
6.677~7.718(m,15H,imidazoleHand Ph-H),8.077(s,1H,N=CH),9.129(s,1H,NCHN),
31
13.238(s,1H,OH)。 P-NMR(200MHz,DMSO4-d6):δ-24.589(s,1P,PPh2);-142.585(m,
13
1P,PF6)。 C-NMR(400MHz,DMSO4-d6):δ22.658(CHMe),36.506(NMe),51.984(Ph-CH2-N),
62.658(CHMe),69.865,70.237,72.081,75.381,117.389,118.684,122.735,124.526,
127.871,128.126,128.302,128.931.129.963,132.501,135.344,136.975,137.409,+ -
139.242,161.420,163.500.ESI m:z = 612M,m:z = 145M 。Anal.Calc.for C36H35F6FeN3P2:C,57.08;H,4.66;N,5.55.Found:C,57.29;H,4.80;N,5.61.[0038] (S,Rp)-1-甲基-3-[(4-二茂铁基亚胺)-2-羟基-卞基]-1H-咪唑六氟磷酸盐
25
制备方法同上,产率93%。[α]D =+308.95(c=0.6,CH2Cl2)。
1
燥。产率96%。m.p.=102~105℃。H-NMR(300MHz,DMSO4-d6):δ3.972(s,3H,CH3),
5.959(s,2H,CH2),7.524(d,2H,J = 7.8Hz,Ph-H),7.837(s,1H,imidazoleH),7.884(s,
1H,imidazoleH),8.325(d,2H,J=7.8Hz,Ph-H),8.738(s,1H,Ph-H),9.269(s,1H,NCHN),+ -
10.208(s,1H,CHO)。ESI:m:z=246M,m:z=145M。
品。产率94%。m.p.=178~179℃。[α]D =-330.70(c=0.6,CH2Cl2)。H-NMR(300MHz,DMSO4-d6):δ1.570(d,3H,J=6.6Hz,CHCH3),3.902(s,3H,CH3),4.072(s,5H,unsubstrated Cp-H),3.670-4.684(m,3H,substrated Cp-H),4.851(m,1H,CHMe),5.759(s,2H,CH2),
6.690~7.836(m,15H,imidazoleH and Ph-H),8.189(s,1H,N=CH),9.152(s,1H,NCHN)。
31 13
P-NMR(200MHz,DMSO4-d6):δ-23.898(s,1P,PPh2);-142.885(m,1P,PF6)。C-NMR(400MHz,DMSO4-d6):δ23.309(CHMe),39.976(NMe),53.148(Ph-CH2-N),61.945(CHMe),70.644,
69.650,71.690,75.447,122.854,124.579,127.658,128.126,128.394,128.709.129.684,
132.302,135.436,136.721,137.219,137.687,139.753,149.232,159.981.ESIm:z =+ -
641M,m:z=145M。Anal.Calc.for C36H34F6FeN4O2P2:C,54.98;H,4.36;N,7.12.Found:
C,54.79;H,4.70;N,7.46.
制备方法同上,产率93%。[α]D =+329.95(c=0.6,CH2Cl2)。
90~92℃。H-NMR(300MHz,DMSO4-d6):δ3.909(s,3H,CH3),5.889(s,2H,CH2),7.454(d,
1H,J=7.8Hz,Ph-H),7.809(s,1H,imidazoleH),7.763(s,1H,imidazoleH),8.266(d,1H,J=7.8Hz,Ph-H),8.684(s,1H,Ph-H),9.168(s,1H,NCHN),10.144(s,1H,CHO)。ESI:m:z=+ -
201M,m:z=145M。
率93 %。m.p.= 96~99 ℃。[α]D =-329.81(c =0.6,CH2Cl2)。H-NMR(300MHz,ACTONE-d6):δ1.680(d,3H,J=6.6Hz,CHCH3),4.101~4.140(m,8H,CH3 and unsubstrated Cp-H),3.833-4.737(m,3H,substratedCp-H),4.909(m,1H,CHMe),5.560(s,2H,CH2),
6.810~7.817(m,16H,imidazoleHand Ph-H),8.110(s,1H,N=CH),9.186(s,1H,NCHN)。
31 13
P-NMR(200MHz,DMSO4-d6):δ-23.798(s,1P,PPh2);-142.985(m,1P,PF6)。C-NMR(400MHz,DMSO4-d6):δ22.309(CHMe),39.796(NMe),52.148(Ph-CH2-N),63.945(CHMe),69.644,
69.650,71.690,75.447,122.754,124.579,127.658,128.126,128.394,128.709.129.684,+
132.302,135.436,136.721,137.219,137.687,139.753,158.911.ESIm:z=596M,m:z=-
145M。Anal.Calc.for C36H35F6FeN3P2:C,58.31;H,4.76;N,5.67.Found:C,57.79;H,
4.80;N,5.66.
上,产率93%。[α]D =+329.95(c=0.6,CH2Cl2)。
6mmol)水溶液,室温反应3h,有白色固体析出,过滤,蒸馏水充分洗涤固体,产品真空干燥。
1
产率90%。m.p.=147~150℃。H-NMR(300MHz,DMSO4-d6):δ3.888(s,3H,CH3);3.985(s,
3H,OMe),5.444(s,2H,CH2),7.360(d,1H,J = 8.7Hz,Ph-H),7.737 ~ 7.871(m,4H,Ph-H +
andimidazoleH),9.222(s,1H,NCHN),10.402(s,1H,CHO)。ESI:m:z=231M,m:z=145M。
产品。产率93%。m.p.=143~144℃。[α]D =-314.75。H-NMR(300MHz,DMSO4-d6):
δ1.615(d,3H,J = 6.6Hz,CHCH3),3.588(s,3H,CH3);3.863(s,3H,CH3),4.081(s,5H,unsubstrated Cp-H),3.756-4.695(m,3H,substrated Cp-H),4.772(m,1H,CHMe),
5.219(s,2H,CH2),6.677~7.718(m,15H,imidazoleH and Ph-H),8.077(s,1H,N=CH),
31
9.129(s,1H,NCHN)。 P-NMR(200MHz,DMSO4-d6):δ-23.798(s,1P,PPh2);-142.985(m,
13
1P,PF6)。 C-NMR(400MHz,DMSO4-d6):δ22.309(CHMe),39.796(NMe),52.148(Ph-CH2-N),
55.207(OMe),63.945(CHMe),69.644,69.650,71.690,75.447,122.754,124.579,
127.658,128.126,128.394,128.709.129.684,132.302,135.436,136.721,137.219,+ -
137.687,139.753,158.911,161.213.ESIm:z = 626M,m:z = 145M。Anal.Calc.for C36H35F6FeN3P2:C,57.60;H,4.83;N,5.45.Found:C,57.89;H,4.60;N,5.36.[0050] (S,Rp)-1-甲基-3-[(3-二茂铁基亚胺)-4-甲氧基-卞基]-1H-咪唑六氟磷酸
25
盐制备方法同上,产率93%。[α]D =+313.95(c=0.6,CH2Cl2)。
AD-H,正己烷∶异丙醇=90∶10,1.0ml/min),ee值为87.5%。H-NMR(300MHz,CDCl3):
δ3.51(s,3H,COOMe),3.70(s,3H,COOMe),3.94 ~ 3.97(m,1H,CH(COOMe)2),6.29 ~
6.35(m,1H,CH=CH-Ph),6.46-6.50(m,1H,Ph-CH=CH),7.20~7.33(m,10H,Ph-H).[0053] (S,Rp)-1-甲基-3-[(4-二茂铁基亚胺)-卞基]-1H-咪唑六氟磷酸盐为催化剂时,收率:45%,ee值为59.5%。
3-二苯基-2-烯丙基-1-醇的乙酸酯(126mg,0.5mmol)、丙二酸二甲酯(170μl,1.5mmol)、N,O-二(三甲基硅)乙酰胺(BSA)(370μl,1.5mmol)和无水醋酸钾1.0mg,密闭反应24小时。加入饱和氯化铵溶液结束反应,萃取、干燥、浓缩、柱层析分离(洗脱剂:石油醚∶乙酸乙酯=20∶1),纯化得到取代产品。收率:30%,HPLC分析产品对映异构体过量值(ee值)(Chiralpak AD-H,正己烷∶异丙醇=90∶10,1.0ml/min),ee值为25.5%。