CN116178232A - 一种手性羟基硒醚及其不对称合成方法 - Google Patents

一种手性羟基硒醚及其不对称合成方法 Download PDF

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CN116178232A
CN116178232A CN202211584758.5A CN202211584758A CN116178232A CN 116178232 A CN116178232 A CN 116178232A CN 202211584758 A CN202211584758 A CN 202211584758A CN 116178232 A CN116178232 A CN 116178232A
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hydroxyseleno
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刘祈星
刘梦娜
刘悦
王金龙
程征
周海峰
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Hubei Zilan Biomedical Technology Co ltd
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Abstract

本发明涉及一种手性羟基硒醚及其不对称合成方法。该方法以α‑硒酮为原料,手性二胺与金属配合物为催化剂,通过不对称转移氢化的方式合成手性羟基硒醚。该方法操作简便、反应条件温和、原料易合成、底物适应性范围广、对映选择性高,在含硒的手性醇合成方面具有广阔应用前景。

Description

一种手性羟基硒醚及其不对称合成方法
技术领域
本发明属于不对称催化技术领域,具体涉及一种手性羟基硒醚及其不对称合成方法。
背景技术
羟基硒醚是有机合成中的重要中间体,其可以转化为α,β-不饱和酮、1,3-噁唑烷酮、取代1,2-氨基醇,含氧杂环,取代四氢呋喃等多种类型化合物,此外还可用于天然产物的合成,如抗凝血的鞘氨醇,抗有丝分裂剂Siastatin B。
目前手性羟基硒醚的合成主要依靠金属有机硒试剂、二苯二硒、有机硅硒试剂及苯硒酚对环氧化合物的开环或者芳基硒卤对特定构型的烯烃亲电加成,这些方法涉及到敏感的硒试剂或复杂的制备方法,因此还需发展新的合成方法。目前不对称转移氢化方法尚未应用到手性羟基硒醚的合成中,该方法具有操作简单,条件温和,对映选择性高的特点。
发明内容
本发明涉及一种手性羟基硒醚及其不对称合成方法,所述的合成方法以α-硒酮为原料,单磺酰手性二胺配体与金属的配合物为催化剂,甲酸盐的水溶液或甲酸-三乙胺共沸物为氢源,经不对称转移氢化的方式得到手性羟基硒醚,反应式如下:
Figure BDA0003992448300000011
Ar选自
Figure BDA0003992448300000012
中的任意一种;
R1为C1-C10的烷基或芳基;
R2为C1-C10的烷基、C1-C10的烷氧基、卤代烷基、卤素、羟基、氨基、硝基、氰基、羧基、苯基中的任意一种;
上面给出的手性羟基硒醚化合物的定义中,所用术语不论单独使用还是用在复合词中,代表如下取代基:
烷基:指直链或支链烷基;
卤素:指氟、氯、溴、碘中的任意一种;
烷氧基:指直链或支链烷氧基;
卤代烷基:指直链或支链烷基,在这些烷基上的氢原子部分或全部被卤原子取代。
本发明提供的不对称合成方法中所涉及的手性催化剂为(R,R)-或(S,S)-N-单磺酰-二芳基手性乙二胺与过渡金属钌﹑铑或铱的配合物,其结构通式如式Ⅲ、式Ⅳ所示,
Figure BDA0003992448300000021
通式Ⅲ或Ⅳ中,M为Ru、Rh或Ir;
Ar为苯基或对甲氧基、甲基取代苯基、萘基;
R为-CH3、-CF3、-C6H5、4-CH3C6H4、4-CF3C6H4、4-(t-Bu)-C6H4-、3,4-(CH3)2-C6H3-、2,4,6-(CH3)3-C6H2-、2,6-Cl2-C6H3-、2,4,6-(i-Pr)3-C6H2-、-C6F5或萘基;
R’为H、CH3或i-Pr;
L为苯、1,4-二甲基苯、1-甲基-4-异丙基苯、1,3,5-三甲基苯、1,2,3,4,5-五甲基苯、1,2,3,4,5,6-六甲基苯或五甲基环戊二烯;
X为Cl-、[OTf]-、[PF6]-、[BF4]-、[SbF6]-或手性磷酸阴离子,Y为C或O。
进一步优化本发明不对称合成方法的催化剂结构如下所示:
Figure BDA0003992448300000022
本发明提供的不对称合成方法中所用氢源为甲酸/三乙胺任意比例混合物或甲酸钠,优选甲酸/三乙胺=1.1:1。
本发明提供的不对称合成方法中所涉及的溶剂为水、甲醇、乙醇、乙酸乙酯、二氯甲烷、N,N-二甲基甲酰胺、氯仿、甲苯中的任意一种或多种上述溶剂的任意比例混合物,优选二氯甲烷。
本发明提供的不对称合成方法中所涉及的反应温度为0-50℃,反应时间为2-24小时。
本发明首次将不对称转移氢化应用到手性羟基硒醚的不对称合成。本发明与现有技术相比具有以下优点:所用手性二胺配体稳定、合成简单、价格相对便宜;实验操作方便、安全、反应条件温和等。利用本发明提供的方法所得到的手性产物,是重要的有机合成中间体,因而本方法具有重要的工业应用价值。
具体实施方式
下面结合具体实施例,对本发明作进一步说明,但本发明并不限于以下实施例。
本发明所用催化剂来源如下:
催化剂C的合成:0.004mmol N-((1S,2S)-2-氨基-1,2-二苯基乙基)-3-(三氟甲基)苯磺酰胺和0.002mmol二氯双(4-甲基异丙基苯基)钌(II)溶解在0.5mL二氯甲烷中,加入0.004mmol三乙胺,室温下反应30分钟,水洗,水相用1mL二氯甲烷萃取3次,合并后浓缩至干,直接用于催化反应,结构式如下。
催化剂E的合成:方法、步骤同催化剂C的制备,仅N-((1S,2S)-2-氨基-1,2-二苯基乙基)-3-(三氟甲基)苯磺酰胺更换为N-((1S,2S)-2-氨基-1,2-二苯基乙基)-4-甲基苯磺酰胺,二氯双(4-甲基异丙基苯基)钌(II)更换为二氯(五甲基环戊二烯基)合铑(III)二聚体,结构式如下。
催化剂F的合成:方法、步骤同催化剂C的制备,仅N-((1S,2S)-2-氨基-1,2-二苯基乙基)-3-(三氟甲基)苯磺酰胺更换为N-((1S,2S)-2-氨基-1,2-二苯基乙基)-4-甲基苯磺酰胺,二氯双(4-甲基异丙基苯基)钌(II)更换为二氯(五甲基环戊二烯基)合铱(III)二聚体,结构式如下。
催化剂G的合成:方法、步骤同催化剂C的制备,仅N-((1S,2S)-2-氨基-1,2-二苯基乙基)-3-(三氟甲基)苯磺酰胺更换为N-((1S,2S)-2-氨基-1,2-二苯基乙基)-4-甲基苯磺酰胺,二氯双(4-甲基异丙基苯基)钌(II)更换为二氯苯基钌(II)二聚体,结构式如下。
催化剂A、B、D、H为商业购买,结构式如下。
Figure BDA0003992448300000031
实施例1
(R)-1-苯基-2-(苯基硒基)乙烷-1-醇的不对称合成
Figure BDA0003992448300000032
向试管中依次加入0.2mmol的1-苯基-2-(苯基硒基)乙烷-1-酮,2mL溶剂,0.004mmol催化剂,1mmol氢源,密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产物(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=11.95min,t2=12.90min。1H NMR(400MHz,CDCl3):δ=7.55-7.53(m,2H),7.34-7.27(m,8H),4.74(dd,J=9.6,2.0Hz,1H),3.30(dd,J=12.8,4.0Hz,1H),3.13(dd,J=12.8,9.2Hz,1H),2.83(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=142.5,133.1,129.3,129.1,128.6,128.0,127.4,125.8,72.2,38.5ppm.
Figure BDA0003992448300000041
实施例2
(R)-2-(苯基硒基)-1-(对甲苯基)乙烷-1-醇的不对称合成
Figure BDA0003992448300000042
向试管中依次加入0.2mmol的2-(苯基硒基)-1-(对甲苯基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:81%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为98%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=9.42min,t2=10.38min。1H NMR(400MHz,CDCl3):δ=7.54-7.52(m,2H),7.28-7.21(m,5H),7.13(d,J=8.0Hz,2H),4.71(dd,J=9.2,4.0Hz,1H),3.27(dd,J=12.8,3.6Hz,1H),3.13(dd,J=12.8,9.6Hz,1H),2.81(s,1H),2.33(s,3H)ppm;13C NMR(100MHz,CDCl3):δ=139.6,137.7,133.11,133.06,129.3,129.2,127.4,125.8,72.1,38.4,21.2ppm.
实施例3
(R)-1-(4-乙基苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
Figure BDA0003992448300000051
向试管中依次加入0.2mmol的1-(4-乙基苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:70%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为99%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=11.48min,t2=12.34min。1H NMR(400MHz,CDCl3):δ=7.54-7.52(m,2H),7.27-7.24(m,5H),7.16(d,J=8.0Hz,2H),4.73(d,J=8.0Hz,1H),3.29(dd,J=12.8,4.0Hz,1H),3.14(dd,J=12.8,9.6Hz,1H),2.77(d,J=2.0Hz,1H),2.63(q,J=7.6Hz,2H),1.22(t,J=7.6Hz,3H)ppm;13CNMR(100MHz,CDCl3):δ=144.1,139.8,133.1,129.30,129.26,128.1,127.3,125.8,72.2,38.4,28.6,15.6ppm.
实施例4
(R)-1-(4-异丙基苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
Figure BDA0003992448300000052
向试管中依次加入0.2mmol的1-(4-异丙基苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:72%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为99%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=10.65min,t2=11.35min。1H NMR(400MHz,CDCl3):δ=7.54-7.51(m,2H),7.27-7.25(m,5H),7.19(d,J=8.0Hz,2H),4.73(dd,J=9.6,2.4Hz,1H),3.29(dd,J=12.8,4.0Hz,1H),3.15(dd,J=12.8,9.2Hz,1H),2.92-2.85(m,1H),2.76(d,J=2.0Hz,1H),1.23(d,J=6.8Hz,6H)ppm;13CNMR(100MHz,CDCl3):δ=148.7,139.9,130.0,129.3,129.2,127.3,126.6,125.9,72.2,38.3,33.9,24.0ppm.
实施例5
(R)-1-(4-(叔丁基)苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
Figure BDA0003992448300000061
向试管中依次加入0.2mmol的1-(4-(叔丁基)苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:72%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为98%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=12.06min,t2=13.44min。1H NMR(400MHz,CDCl3):δ=7.54-7.51(m,2H),7.36-7.34(m,2H),7.28-7.24(m,5H),4.73(dd,J=8.8,1.6Hz,1H),3.30(dd,J=12.4,4.0Hz,1H),3.15(dd,J=12.8,9.6Hz,1H),2.78(d,J=2.4Hz 1H),1.30(s,9H)ppm;13C NMR(100MHz,CDCl3):δ=150.9,139.5,133.0,129.3,129.2,127.3,125.6,125.5,72.1,38.3,34.6,31.4ppm.
实施例6
(R)-1-([1,1'-联苯]-4-基)-2-(苯基硒基)乙烷-1-醇的不对称合成
Figure BDA0003992448300000062
向试管中依次加入0.2mmol的1-([1,1'-联苯]-4-基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:67%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为95%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=31.43min,t2=34.57min。1H NMR(400MHz,CDCl3):δ=7.58-7.53(m,6H),7.44-7.38(m,4H),7.36-7.32(m,1H),7.28-7.26(m,3H),4.78(dd,J=9.2,3.6Hz,1H),3.33(dd,J=12.8,3.6Hz,1H),3.16(dd,J=12.8,9.2Hz,1H),2.90(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=141.5,140.9,140.8,133.2,129.3,129.1,128.8,127.5,127.4,127.3,127.1,126.3,72.0,38.5ppm.
实施例7
(R)-1-(4-氟苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
Figure BDA0003992448300000063
向试管中依次加入0.2mmol的1-(4-氟苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:88%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为96%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=14.41min,t2=15.61min。1H NMR(400MHz,CDCl3):δ=7.54-7.51(m,2H),7.31-7.27(m,5H),7.03-6.98(m,2H),4.71(dd,J=9.2,3.6Hz,1H),3.26(dd,J=12.8,4.0Hz,1H),3.09(dd,J=12.8,9.6Hz,1H),2.90(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=162.4(d,JC-F=244.3Hz),138.2(d,JC-F=3.0Hz),133.2,129.3,128.9,127.6(d,JC-F=1.9Hz),127.5,115.4(d,JC-F=21.2Hz),71.6,38.5ppm.
实施例8
(R)-1-(4-氯苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
Figure BDA0003992448300000071
向试管中依次加入0.2mmol的1-(4-氯苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:90%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为94%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=9.95min,t2=10.85min。1H NMR(400MHz,CDCl3):δ=7.53-7.51(m,2H),7.29-7.23(m,7H),4.69(dd,J=9.2,4.0Hz,1H),3.24(dd,J=12.8,3.6Hz,1H),3.06(dd,J=12.8,9.2Hz,1H),2.98(brs,1H)ppm;13C NMR(100MHz,CDCl3):δ=140.9,133.6,133.3,129.4,128.8,128.7,127.6,127.2,71.5,38.4ppm.
实施例9
(R)-1-(4-溴苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
Figure BDA0003992448300000072
向试管中依次加入0.2mmol的1-(4-溴苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:91%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为95%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=10.49min,t2=11.52min。1H NMR(400MHz,CDCl3):δ=7.53-7.51(m,2H),7.43(d,J=8.4Hz,2H),7.28-7.27(m,3H),7.19(d,J=8.0Hz,2H),4.67(dd,J=9.6,3.6Hz,1H),3.24(dd,J=12.8,3.6Hz,1H),3.06(dd,J=12.8,9.2Hz,1H),2.94(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=141.4,133.3,131.6,129.4,128.8,127.6,121.7,71.5,38.4ppm.
实施例10
(R)-1-(3-甲氧基苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
Figure BDA0003992448300000081
向试管中依次加入0.2mmol的1-(3-甲氧基苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:95%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为98%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=17.11min,t2=18.84min。1H NMR(400MHz,CDCl3):δ=7.54-7.52(m,2H),7.27-7.24(m,4H),6.90-6.88(m,2H),6.82-6.79(m,2H),4.72(dd,J=9.4,3.6Hz,1H),3.78(s,3H),3.29(dd,J=12.8,3.6Hz,1H),3.13(dd,J=12.8,9.6Hz,1H),2.85(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=159.8,144.2,133.1,129.6,129.3,127.4,118.1,113.4,111.3,72.2,55.3,38.4ppm.
实施例11
(R)-1-(3-氯苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
Figure BDA0003992448300000082
向试管中依次加入0.2mmol的1-(3-氯苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:83%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为96%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=8.55min,t2=9.37min。1H NMR(400MHz,CDCl3):δ=7.55-7.53(m,2H),7.34-7.33(m,1H),7.30-7.28(m,3H),7.25-7.23(m,2H),7.20-7.18(m,1H),4.70(dd,J=9.2,3.6Hz,1H),3.27(dd,J=12.8,4.0Hz,1H),3.07(dd,J=12.8,9.2Hz,1H),2.93(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=144.5,134.4,133.3,129.8,129.3,128.7,128.0,127.6,126.0,124.0,71.5,38.4ppm.
实施例12
(R)-1-(3-溴苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
Figure BDA0003992448300000091
向试管中依次加入0.2mmol的1-(3-溴苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:88%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为98%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=8.48min,t2=9.37min。1H NMR(400MHz,CDCl3):δ=7.57-7.51(m,3H),7.41(d,J=8.0Hz,1H),7.31-7.18(m,5H),4.69(d,J=7.6Hz,1H),3.28(dd,J=12.8,3.6Hz,1H),3.08(m,1H),2.98(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=144.7,133.3,131.0,130.1,129.4,129.0,128.7,127.7,124.5,122.7,71.4,38.4ppm.
实施例13
(R)-1-(2-乙基苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
Figure BDA0003992448300000092
向试管中依次加入0.2mmol的1-(2-乙基苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:70%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为98%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=10.84min,t2=11.43min。1H NMR(400MHz,CDCl3):δ=7.55-7.52(m,2H),7.29-7.23(m,4H),7.17-7.11(m,3H),4.72(dd,J=8.8,2.8Hz,1H),3.30(dd,J=12.8,3.6Hz,1H),3.14(dd,J=12.8,3.6Hz,1H),2.83(s,1H),2.63(q,J=7.6Hz,2H),1.22(t,J=7.6Hz,3H)ppm;13C NMR(100MHz,CDCl3):δ=144.6,142.5,133.1,129.3,128.5,128.1,127.4,125.9,125.3,123.2,72.3,38.5,28.9,15.6ppm.
实施例14
(R)-1-(2-甲氧基苯基)-2-(苯基硒基)乙烷-1-醇的不对称合成
Figure BDA0003992448300000093
向试管中依次加入0.2mmol的1-(2-甲氧基苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:57%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为96%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=98:2(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=34.56min,t2=36.14min。1H NMR(400MHz,CDCl3):δ=7.57-7.55(m,2H),7.45(dd,J=7.2,1.6Hz,1H),7.30-7.26(m,4H),7.00(td,J=7.2,0.8Hz,1H),6.86(d,J=8.0Hz,1H),5.09-5.05(m,1H),3.82(s,3H),3.48(dd,J=12.8,4.0Hz,1H),3.16(dd,J=12.8,9.2Hz,1H),3.07(d,J=4.8Hz,1H)ppm;13C NMR(100MHz,CDCl3):δ=156.1,132.4,130.4,129.9,129.0,128.7,126.8,126.7,120.8,110.3,69.0,55.2,36.1ppm.
实施例15
(R)-2-(1-羟基-2-(苯基硒基)乙基)苯酚的不对称合成
Figure BDA0003992448300000101
向试管中依次加入0.2mmol的1-(2-羟基苯基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:61%(石油醚:乙酸乙酯=10:1),HPLC测定产物ee值为98%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=24.61min,t2=25.89min。1H NMR(400MHz,CDCl3):δ=7.95(s,1H),7.57-7.55(m,2H),7.32-7.30(m,3H),7.19-7.15(m,1H),6.89-6.79(m,3H),4.77(dd,J=10.4,3.2Hz,1H),3.68(s,1H),3.33(dd,J=13.2,3.6Hz,1H),3.24(dd,J=13.2,10.4Hz,1H)ppm;13C NMR(100MHz,CDCl3):δ=155.4,133.3,129.5,129.4,128.1,127.8,127.3,125.0,120.0,117.5,73.3,36.9ppm.
实施例16
(R)-1-(萘-2-基)-2-(苯基硒基)乙烷-1-醇的不对称合成
Figure BDA0003992448300000102
向试管中依次加入0.2mmol的1-(萘-2-基)-2-(苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:84%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为95%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=11.89min,t2=13.03min。1H NMR(400MHz,CDCl3):δ=7.82-7.80(m,4H),7.58-7.56(m,2H),7.48-7.43(m,3H),7.29-7.27(m,3H),4.91(dd,J=9.2,3.6Hz,1H),3.39(dd,J=12.8,4.0Hz,1H),3.21(dd,J=12.8,9.2Hz,1H),2.95(brs,1H)ppm;13C NMR(100MHz,CDCl3):δ=139.8,133.3,133.2,133.1,129.3,129.0,128.4,128.0,127.7,127.5,126.2,126.0,124.7,123.8,72.3,38.5ppm.
实施例17
(R)-2-(苯基硒基)-1-(吡啶-4-基)乙烷-1-醇的不对称合成
Figure BDA0003992448300000111
向试管中依次加入0.2mmol的2-(苯基硒基)-1-(吡啶-4-基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:60%(石油醚:乙酸乙酯=1:1),HPLC测定产物ee值为99%。HPLC分离条件:手性AD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=42.64min,t2=47.09min。1H NMR(400MHz,CDCl3):δ=8.50-8.48(m,2H),755-7.53(m,2H),7.30-7.27(m,5H),4.76(dd,J=9.2,4.0Hz,1H),3.29(dd,J=12.8,4.0Hz,1H),3.10(dd,J=12.8,8.8Hz,1H)ppm;13C NMR(100MHz,CDCl3):δ=151.9,149.6,133.31,133.26,129.4,128.8,127.7,121.0,70.8,37.8ppm.
实施例18
(R)-2-(苯基硒基)-1-(噻吩-3-基)乙烷-1-醇的不对称合成
Figure BDA0003992448300000112
向试管中依次加入0.2mmol的2-(苯基硒基)-1-(噻吩-3-基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:46%(石油醚:乙酸乙酯=7:1),HPLC测定产物ee值为97%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=98:2(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=37.75min,t2=39.83min。1H NMR(400MHz,CDCl3):δ=7.54-7.52(m,2H),7.29-7.22(m,5H),7.05-7.04(m,1H),4.86(dd,J=8.8,3.6Hz,1H),3.33(dd,J=12.4,4.0Hz,1H),3.19(dd,J=12.8,8.8Hz,1H),2.84(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=143.8,133.2,129.3,129.2,127.4,126.3,125.5,121.3,68.7,37.8ppm.
实施例19
(R)-1-(苯基硒基)丙-2-醇的不对称合成
Figure BDA0003992448300000121
向试管中依次加入0.2mmol的1-(苯基硒基)丙-2-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:37%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为28%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=7.60min,t2=10.69min。1HNMR(400MHz,CDCl3):δ=7.57-7.54(m,2H),7.30-7.28(m,3H),3.91-3.85(m,1H),3.13(dd,J=12.8,4.0Hz,1H),2.90(dd,J=12.8,8.4Hz,1H),2.49(brs,1H),1.30(d,J=6.4Hz,3H)ppm;13C NMR(100MHz,CDCl3):δ=133.1,129.2,127.3,66.0,38.6ppm.
实施例20
(R)-2-((4-甲基苯基)硒基)-1-苯基乙烷-1-醇的不对称合成
Figure BDA0003992448300000122
向试管中依次加入0.2mmol的1-苯基-2-(对甲苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.010mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:89%(石油醚:乙酸乙酯=30:1),HPLC测定产物ee值为97%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=11.70min,t2=13.60min。1H NMR(400MHz,CDCl3):δ=7.45(d,J=8.0Hz,2H),7.33-7.26(m,5H),7.10(d,J=7.8Hz,2H),4.71(dd,J=9.6,3.6Hz,1H),3.25(dd,J=12.8,3.6Hz,1H),3.08(dd,J=12.8,9.6Hz,1H),2.87(s,1H),2.33(s,3H)ppm;13C NMR(100MHz,CDCl3):δ=142.5,137.6,133.6,130.1,128.5,127.9,125.8,125.1,72.1,38.9,21.1ppm.
实施例21
(R)-2-((4-甲氧基苯基)硒基)-1-苯基乙烷-1-醇的不对称合成
Figure BDA0003992448300000123
向试管中依次加入0.2mmol的2-((4-甲氧基苯基)硒基)-1-苯基乙烷-1-酮,2mL二氯甲烷,0.010mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:93%(石油醚:乙酸乙酯=10:1),HPLC测定产物ee值为98%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=11.14min,t2=12.23min。1H NMR(400MHz,CDCl3):δ=7.51-7.48(m,2H),7.34-7.25(m,5H),6.84-6.81(m,2H),4.67(dd,J=9.6,3.6Hz,1H),3.79(s,3H),3.19(dd,J=12.8,3.6Hz,1H),3.03(dd,J=12.8,9.6Hz,1H),2.91(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=159.6,142.5,136.0,128.5,127.9,125.9,118.8,115.0,72.0,55.3,39.6ppm.
实施例22
(R)-2-((4-氟苯基)硒基)-1-苯基乙烷-1-醇的不对称合成
Figure BDA0003992448300000131
向试管中依次加入0.2mmol的2-((4-氟苯基)硒基)-1-苯基乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:95%(石油醚:乙酸乙酯=30:1),HPLC测定产物ee值为96%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=18.12min,t2=20.66min。1H NMR(400MHz,CDCl3):δ=7.53-7.50(m,2H),7.34-7.28(m,5H),7.00-6.96(m,2H),4.72(dd,J=9.2,3.6Hz,1H),3.24(dd,J=12.8,3.6Hz,1H),3.11(dd,J=12.8,9.2Hz,1H),2.78(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=162.6(d,JC-F=246.1Hz),142.3,135.8(d,JC-F=7.9Hz),128.6,128.0,125.8,123.5,116.5(d,JC-F=21.5Hz),72.2,39.2ppm.
实施例23
(R)-2-((4-氯苯基)硒基)-1-苯基乙烷-1-醇的不对称合成
Figure BDA0003992448300000132
向试管中依次加入0.2mmol的2-((4-氯苯基)硒基)-1-苯基乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:92%(石油醚:乙酸乙酯=30:1),HPLC测定产物ee值为94%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=15.65min,t2=17.56min。1H NMR(400MHz,CDCl3):δ=7.45-7.43(m,2H),7.34-7.28(m,5H),7.24-7.22(m,2H),4.75(dd,J=9.2,3.6Hz,1H),3.26(dd,J=12.8,4.0Hz,1H),3.14(dd,J=12.8,9.2Hz,1H),2.77(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=142.3,134.5,133.6,129.4,128.6,128.1,127.4,125.8,72.4,38.6ppm.
实施例24
(R)-1-苯基-2-(间甲苯基硒基)乙烷-1-醇的不对称合成
Figure BDA0003992448300000141
向试管中依次加入0.2mmol的1-苯基-2-(间甲苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.010mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:95%(石油醚:乙酸乙酯=30:1),HPLC测定产物ee值为95%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=13.98min,t2=15.46min。1H NMR(400MHz,CDCl3):δ=7.54-7.52(m,1H),7.39-7.30(m,5H),7.24-7.13(m,3H),4.79(dd,J=9.6,4.0Hz,1H),3.30(dd,J=12.8,4.0Hz,1H),3.16(dd,J=12.4,9.2Hz,1H),2.91(s,1H),2.45(s,3H)ppm;13C NMR(100MHz,CDCl3):δ=142.6,139.8,132.3,130.25,130.19,128.6,128.0,127.3,126.7,125.8,72.3,37.2,22.6ppm.
实施例25
(R)-2-((3-氯苯基)硒基)-1-苯基乙烷-1-醇的不对称合成
Figure BDA0003992448300000142
向试管中依次加入0.2mmol的2-((3-氯苯基)硒基)-1-苯基乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:46%(石油醚:乙酸乙酯=30:1),HPLC测定产物ee值为96%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=17.40min,t2=18.30min。1H NMR(400MHz,CDCl3):δ=7.48(t,J=1.6Hz,1H),7.38(dt,J=7.2,1.6Hz,1H),7.35-7.26(m,5H),7.24-7.16(m,2H),4.79(dd,J=8.8,4.0Hz,1H),3.30(dd,J=12.8,4.0Hz,1H),3.19(dd,J=12.8,8.8Hz,1H),2.74(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=142.3,134.8,132.4,131.2,130.7,130.2,128.6,128.1,127.4,125.8,72.5,38.2ppm.
实施例26
(R)-1-苯基-2-((3-(三氟甲基)苯基)硒基)乙烷-1-醇的不对称合成
Figure BDA0003992448300000151
向试管中依次加入0.2mmol的1-苯基-2-((3-(三氟甲基)苯基)硒基)乙烷-1-酮,2mL二氯甲烷,0.010mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:93%(石油醚:乙酸乙酯=30:1),HPLC测定产物ee值为92%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=13.14min,t2=14.40min。1H NMR(400MHz,CDCl3):δ=7.76(s,1H),7.70(d,J=8.0Hz,1H),7.52(d,J=7.6Hz,1H),7.41-7.30(m,6H),4.85(dd,J=8.8,4.0Hz,1H),3.36(dd,J=12.8,4.0Hz,1H),3.26(dd,J=12.8,8.8Hz,1H),2.76(s,1H)ppm;13C NMR(100MHz,CDCl3):δ=142.3,135.8,131.4(q,JC-F=32.1Hz),130.8,129.4,129.1(q,JC-F=3.8Hz),128.7,128.2,125.8,123.9(q,JC-F=271.1Hz),123.6(q,JC-F=3.7Hz)ppm.
实施例27
(R)-1-苯基-2-(邻甲苯基硒基)乙烷-1-醇的不对称合成
Figure BDA0003992448300000152
向试管中依次加入0.2mmol的1-苯基-2-(邻甲苯基硒基)乙烷-1-酮,2mL二氯甲烷,0.010mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:90%(石油醚:乙酸乙酯=30:1),HPLC测定产物ee值为96%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=13.98min,t1=15.55min。1H NMR(400MHz,CDCl3):δ=7.35-7.27(m,7H),7.17(t,J=8.0Hz,1H),7.08(d,J=6.8Hz,1H),4.74(dd,J=9.6,3.6Hz,1H),3.30(dd,J=12.8,3.6Hz,1H),3.12(dd,J=12.8,9.6Hz,1H),2.87(s,1H),2.33(s,3H)ppm;13C NMR(100MHz,CDCl3):δ=142.5,139.1,133.8,130.1,129.1,128.8,128.5,128.3,127.9,125.8,72.2,38.5,21.3ppm.
实施例28
(R)-2-((3,5-二甲基苯基)硒基)-1-苯基乙烷-1-醇的不对称合成
Figure BDA0003992448300000153
向试管中依次加入0.2mmol的2-((3,5-二甲基苯基)硒基)-1-苯基乙烷-1-酮,2mL二氯甲烷,0.010mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:82%(石油醚:乙酸乙酯=30:1),HPLC测定产物ee值为98%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=10.10min,t2=11.84min。1H NMR(400MHz,CDCl3):δ=7.35-7.34(m,4H),7.31-7.27(m,1H),7.15(s,2H),6.90(s,1H),4.74(dd,J=9.6,4.0Hz,1H),3.29(dd,J=12.8,4.0 1H),3.11(dd,J=12.8,9.6Hz,1H),2.89(s,1H),2.29(s,6H)ppm;13C NMR(100MHz,CDCl3):δ=142.5,138.9,130.8,129.3,128.5,127.9,125.8,72.2,38.4,21.2ppm.
实施例29
(R)-2-(萘-2-基硒基)-1-苯基乙烷-1-醇的不对称合成
Figure BDA0003992448300000161
向试管中依次加入0.2mmol的2-(萘-2-基硒基)-1-苯基乙烷-1-酮,2mL二氯甲烷,0.010mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:95%(石油醚:乙酸乙酯=20:1),HPLC测定产物ee值为97%。HPLC分离条件:手性AD-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=10.75min,t2=12.14min。1H NMR(400MHz,CDCl3):δ=8.40(d,J=8.4Hz,1H),7.85-7.80(m,3H),7.58-7.49(m,2H),7.39-7.35(m,1H),7.29-7.22(m,5H),4.70(dd,J=9.2,3.6Hz,1H),3.30(dd,J=12.8,4.0Hz,1H),3.18(dd,J=12.8,9.6Hz,1H),2.83(s,1H).ppm;13C NMR(100MHz,CDCl3):δ=142.5,134.3,134.1,133.2,128.9,128.8,128.5,128.3,127.9,127.6,126.9,126.4,125.84,125.81,72.4,38.4ppm.
实施例30
(R)-1-苯基-2-(吡啶-2-基硒基)乙烷-1-醇的不对称合成
Figure BDA0003992448300000162
向试管中依次加入0.2mmol的1-苯基-2-(吡啶-2-基硒基)乙烷-1-酮,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:96%(石油醚:乙酸乙酯=5:1),HPLC测定产物ee值为96%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=95:5(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=20.93min,t2=23.41min。1H NMR(400MHz,CDCl3):δ=8.45-8.43(m,1H),7.50-7.42(m,4H),7.37-7.33(m,2H),7.29-7.25(m,1H),7.12-7.08(m,1H),6.54(s,1H),5.17(dd,J=8.0,3.2Hz,1H),3.50(dd,J=13.6,2.8Hz,1H),3.40(dd,J=14.0,7.6Hz,1H)ppm;13C NMR(100MHz,CDCl3):δ=155.4,149.6,144.6,136.5,128.3,127.4,126.0,125.9,120.9,74.3,36.4ppm.
实施例31
4-((R)-1-羟基-2-(苯基硒基)乙基)苯基(S)-2-((叔丁氧基羰基)氨基)-3,3-二甲基丁酸酯
Figure BDA0003992448300000171
向试管中依次加入0.2mmol的4-(2-(苯基硒基)乙酰基)苯基(S)-2-((叔丁氧基羰基)氨基)-3,3-二甲基丁酸酯,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:70%(石油醚:乙酸乙酯=5:1),HPLC测定产物ee值为94%。HPLC分离条件:手性OD-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=9.60min,t2=10.61min。1H NMR(400MHz,CDCl3):δ=7.54-7.52(m,2H),7.35(d,J=8.4Hz,2H),7.28-7.26(m,3H),7.07(d,J=8.4Hz,2H),5.17(d,J=9.2Hz,1H),4.74(dd,J=9.2,3.2Hz,1H),4.31(d,J=9.2Hz,1H),3.27(dd,J=12.8,3.8Hz,1H),3.10(dd,J=12.8,9.2Hz,1H),2.91(s,1H),1.46(s,9H),1.09(s,9H).ppm;13C NMR(100MHz,CDCl3):δ=170.6,155.6,149.9,140.4,133.2,129.3,129.0,127.5,127.0,121.5,80.1,71.7,61.8,38.4,35.0,29.7,28.3,26.7ppm.
实施例32
(1R,2S,5R)-2-异丙基-5-甲基环己基4-((R)-1-羟基-2-(苯基硒基)乙基)苯甲酸酯
Figure BDA0003992448300000172
向试管中依次加入0.2mmol的(1R,2S,5R)-2-异丙基-5-甲基环己基4-(2-(苯基硒基)乙酰基)苯甲酸酯,2mL二氯甲烷,0.004mmol催化剂B,1mmol甲酸/三乙胺(1.1:1),密封,35℃反应12h。反应结束后用饱和碳酸氢钠溶液洗涤,水相用二氯甲烷萃取3次,合并有机相浓缩至干,分离产率:92%(石油醚:乙酸乙酯=15:1),HPLC测定产物ee值为90%。HPLC分离条件:手性IA-H柱,流动相:正己烷/异丙醇=90:10(体积比),流速:1.0mL/min,波长:254nm,柱温:30℃,t1=12.29min,t2=16.73min。1H NMR(400MHz,CDCl3):δ=7.99(d,J=8.4Hz,2H),7.54-7.52(m,2H),7.39(d,J=8.4Hz,2H),7.29-7.26(m,2H),4.92(td,J=10.8,4.4Hz,1H),4.79(dd,J=9.2,3.6Hz,1H),3.29(dd,J=12.8,4.0Hz,1H),3.10(dd,J=12.8,9.2Hz,1H),3.00(s,1H),2.12-2.09(m,1H),1.98-1.91(m,1H),1.75-1.68(m,2H),1.75-1.68(m,2H),1.57-1.51(m,2H),0.93-0.90(m,7H),0.79(d,J=7.2 Hz,3H)ppm;13CNMR(100 MHz,CDCl3):δ=165.8,147.3,133.3,130.4,129.8,129.3,128.8,127.6,125.7,74.9,71.8,47.3,41.0,38.4,34.3,31.5,26.5,23.7,22.1,20.8,16.6 ppm.

Claims (9)

1.一种手性羟基硒醚,其特征在于,结构式如下图所示:
Figure FDA0003992448290000011
其中Ar选自
Figure FDA0003992448290000012
中的任意一种。所述的R1为C1-C10的烷基或芳基;R2为C1-C10烷基、C1-C10烷氧基、卤代烷基、卤素、羟基、氨基、硝基、氰基、羧基、苯基中的任意一种;
上面给出的手性羟基硒醚化合物的定义中,所用术语不论单独使用还是用在复合词中,代表如下取代基:
烷基:指直链或支链烷基;
卤素:指氟、氯、溴、碘中的任意一种;
烷氧基:指直链或支链烷氧基;
卤代烷基:指直链或支链烷基,在这些烷基上的氢原子部分或全部被卤原子取代。
2.权利要求1所述的手性羟基硒醚的不对称合成方法,其特征在于,以α-硒酮为原料,溶剂溶解后投入单磺酰手性二胺配体与金属的配合物作催化剂,加入氢源,经不对称转移氢化的方式得到手性羟基硒醚,反应式如下:
Figure FDA0003992448290000013
3.权利要求2所述的手性羟基硒醚的不对称合成方法,其特征在于,所述的化合物Ⅰ或Ⅱ中的Ar选自
Figure FDA0003992448290000014
中的任意一种;
R1为C1-C10的烷基或芳基;
R2为C1-C10的烷基、C1-C10的烷氧基、卤代烷基、卤素、羟基、氨基、硝基、氰基、羧基、苯基中的任意一种。
4.权利要求2所述的手性羟基硒醚的不对称合成方法,其特征在于,所述的金属的配合物的催化剂为(R,R)-或(S,S)-N-单磺酰-二芳基手性乙二胺与过渡金属钌或铑或铱的配合物,其结构通式如式Ⅲ、式Ⅳ所示,
Figure FDA0003992448290000015
通式Ⅲ或Ⅳ中,M为Ru、Rh或Ir;
Ar为苯基或对甲氧基、甲基取代苯基、萘基;
R为-CH3、-CF3、-C6H5、4-CH3C6H4、4-CF3C6H4、4-(t-Bu)-C6H4-、3,4-(CH3)2-C6H3-、2,4,6-(CH3)3-C6H2-、2,6-Cl2-C6H3-、2,4,6-(i-Pr)3-C6H2-、-C6F5或萘基;
R’为H、CH3或i-Pr;
L为苯、1,4-二甲基苯、1-甲基-4-异丙基苯、1,3,5-三甲基苯、1,2,3,4,5-五甲基苯、1,2,3,4,5,6-六甲基苯或五甲基环戊二烯;
X为Cl-、[OTf]-、[PF6]-、[BF4]-、[SbF6]-或手性磷酸阴离子;
Y为C或O。
5.权利要求4所述的手性羟基硒醚的不对称合成方法,其特征在于,单磺酰手性二胺配体与金属的配合物包括如下结构式中的任意一种:
Figure FDA0003992448290000021
6.根据权利要求2所述的手性羟基硒醚的不对称合成方法,其特征在于,所述的氢源为甲酸/三乙胺任意比例混合物或甲酸钠的水溶液。
7.根据权利要求2所述的手性羟基硒醚的不对称合成方法,其特征在于,所述的氢源甲酸与三乙胺以1.1:1形成的混合物。
8.根据权利要求2所述的手性羟基硒醚的不对称合成方法,其特征在于,所用溶剂为水、甲醇、乙醇、乙酸乙酯、二氯甲烷、N,N-二甲基甲酰胺、氯仿、甲苯中的任意一种或多种上述溶剂的任意比例混合物。
9.根据权利要求2所述的手性羟基硒醚的不对称合成方法,其特征在于,不对称转移氢化反应的反应温度为0-50℃,反应时间为2-24小时。
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