CN114057785B - 手性α-二氟甲基硅烷化合物的合成方法 - Google Patents
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Abstract
本发明提供一种手性α‑二氟甲基硅烷3的合成方法,属于有机合成技术领域。以偕二氟烯烃1与二苯基硅烷2为原料,在Ni(COD)2催化剂和手性配体L1存在下,以B(C6F5)3、4A分子筛及对甲氧基苯胺为添加剂,有机溶剂反应得到手性α‑二氟甲基硅烷类化合物3;本发明所用原料简单易得,催化剂廉价且用量少,反应条件相对温和,得到目标产物收率高及对映选择性优秀,弥补了镍催化构建碳sp3‑硅键的不足。
Description
技术领域
本发明涉及有机合成技术领域,具体涉及手性α-二氟甲基硅烷类化合物的合成方法。
背景技术
含氟化合物在药物化学和材料化学中有着非常广泛地应用。二氟甲基是一种氟烷基,可改变分子代谢稳定性和亲脂性,在药物设计中,二氟甲基被认为是羟基和硫醇基团的生物电子等排体,含有二氟甲基的手性分子可以和手性受体(如酶或蛋白质)发生氢键相互作用,从而提高其生物活性。
尽管现在已经有很多合成方法得到含二氟甲基基团的化合物,但是手性含二氟甲基分子的合成还是主 要依赖于酮或者亚胺衍生物与二氟甲基合成子反应 (其中活性基团的脱除需要单独的步骤),或者通过官能团转化得到手性的含有二氟甲基的化合物,这种方法需要底物中含有二氟甲基基团,限制了底物范围。
发明内容
本发明的目的是提供一种简洁高效、条件温和的手性α-二氟甲基硅烷类化合物的合成方法。以偕二氟烯烃1与二苯基硅烷2为原料,在Ni(COD)2催化剂和手性配体存在下,以B(C6F5)3、4A分子筛及对甲氧基苯胺为添加剂,有机溶剂反应得到手性α-二氟甲基硅烷类化合物3;本发明所用原料简单易得,催化剂廉价且用量少,反应条件相对温和,得到目标产物收率高及对映选择性优秀,弥补了镍催化构建碳sp3-硅键的不足。
本发明所述一种手性α-二氟甲基硅烷类化合物3的合成方法,包括如下步骤:以偕二氟烯烃1与二苯基硅烷2为原料,在Ni(COD)2催化剂和手性配体L 存在下,以B(C6F5)3、4A分子筛及对甲氧基苯胺为添加剂,有机溶剂反应得到手性α-二氟甲基硅烷类化合物3;
其中,R为苯基及取代苯基、联苯基及取代联苯基、萘基及取代萘基、噻吩基及取代噻吩基、乙烯基及取代乙烯基;Ar为苯基或取代苯基;前述取代基均选自C1-C4烷基、C1-C4烷氧基、C1-C4烷氧羰基、卤素、苯基、4-三氟甲基苯基或4-甲氧基苯基。
进一步地,在上述技术方案中,所述有机溶剂选自四氢呋喃、甲基叔丁基醚、甲苯、二氧六环。优选条件下,有机溶剂选自甲苯。
进一步地,在上述技术方案中,所述所述偕二氟烯烃1、二苯基硅烷2、 Ni(COD)2、手性配体L、B(C6F5)3及对甲氧基苯胺摩尔比为1:1-2:0.01-0.05: 0.01-0.05:0.02-0.05:0.05-0.1。
进一步地,在上述技术方案中,每mmol偕二氟烯烃1中加入250mg 4A分子筛。
进一步地,在上述技术方案中,所述反应温度为20-40℃。
进一步地,在上述技术方案中,所述反应在惰性气体保护下进行,惰性气体为氩气。
发明有益效果
本发明利用Ni(COD)2催化偕二氟烯烃1与二苯基硅烷2反应制备手性α-二氟甲基硅烷类化合物3。该方法所使用原料简单易得,催化剂廉价且用量少,反应条件也相对温和,目标产物收率高,对映选择性优秀。
具体实施方式
下面结合具体实施例对本发明做进一步地说明,但实施例并不对本发明作任何形式的限定。
条件优化实验(以1a和2a反应为例)
在氩气氛围下,在真空封管中加入Ni(COD)2(5mol%),L(5mol%),有机溶剂(1.5mL),室温搅拌30分钟,加入B(C6F5)3(5mol%),室温搅拌30分钟,加入化合物2a(0.04mmol,1mol/L,48μL),室温搅拌10分钟,加入化合物2a(0.36 mmol,1mol/L,0.43mL),4A分子筛(50mg),对甲氧基苯胺(10mol%)和化合物 1a(0.2mmol)。置于30℃油浴搅拌24h,将反应混合物通过硅藻土过滤,用二氯甲烷及乙酸乙酯洗脱,经过减压蒸馏浓缩后,柱层析(PE:EA=100:1)纯化得到目标产物3a。反应结果如下:
经过优化后,确定最佳反应条件为:
在氩气氛围下,在真空封管中加入Ni(COD)2(5mol%),L1(5mol%),甲苯(1.5mL),室温搅拌30分钟。加入B(C6F5)3(5mol%),室温搅拌30分钟,加入化合物2(0.04mmol),室温搅拌10分钟,加入化合物2(0.36mmol),4A分子筛(50mg),对甲氧基苯胺(10mol%)和化合物1(0.2mmol)。置于30℃油浴搅拌24h,将反应混合物通过硅藻土过滤,用二氯甲烷及乙酸乙酯洗脱,经过减压蒸馏浓缩后,柱层析(PE:EA=100:1)纯化得到目标产物。
实施例1
在氩气氛围下,在真空封管中加入Ni(COD)2(5mol%),L1(5mol%),甲苯(1.5mL),室温搅拌30分钟,加入B(C6F5)3(5mol%),室温搅拌30分钟,加入化合物2a(0.04mmol,1mol/L,48μL),室温搅拌10分钟,加入化合物2a(0.36mmol, 1mol/L,0.43mL),4A分子筛(50mg),对甲氧基苯胺(10mol%)和化合物1a(0.2 mmol)。置于30℃油浴搅拌24h,将反应混合物通过硅藻土过滤,二氯甲烷及乙酸乙酯洗脱,经过减压蒸馏浓缩后,柱层析(PE:EA=100:1)纯化得到目标产物3a。无色油状物(产率99%/95%ee);NY(2)-RH 5u(CH3CN/H2O=80/20,0.7mL/min): tR=6.7min(major),tR=8.1min.[α]D 27=43.9(c 0.83,CHCl3).1HNMR(400MHz, CDCl3):7.60-7.55(m,2H),7.46-7.41(m,1H),7.40-7.32(m,5H),7.30-7.21(m,4H), 7.01(d,J=8.4Hz,2H),6.08(td,J=57.2,4.4Hz,1H),5.07(d,J=2.5Hz,1H),3.34-3.16(m,1H),1.28(s,9H).19F NMR(377MHz,CDCl3):-107.34/-109.28(m, 2F).13C NMR(101MHz,CDCl3):149.6,135.9,135.7,131.7(t,J=5.1Hz),130.3, 130.1,129.6,129.2,128.3,128.2,128.0,125.7,118.6(t,J=243.4Hz),40.8(t,J= 19.2Hz),34.5,31.5.HRMS(ESI,m/z):calcd for C24H26F2NaSi+[M+Na]+: 403.1664,found:403.1664.
实施例2
在氩气氛围下,在真空封管中加入Ni(COD)2(5mol%),L1(5mol%),甲苯(1.5mL),室温搅拌30分钟,加入B(C6F5)3(5mol%),室温搅拌30分钟,加入化合物2a(0.04mmol,1mol/L,48μL),室温搅拌10分钟,加入化合物2a(0.36mmol, 1mol/L,0.43mL),4A分子筛(50mg),对甲氧基苯胺(10mol%)和化合物1b(0.2 mmol)。置于30℃油浴搅拌24h,将反应混合物通过硅藻土过滤,二氯甲烷及乙酸乙酯洗脱,经过减压蒸馏浓缩后,柱层析(PE:EA=100:1)纯化得到目标产物3b。无色油状物(产率99%/95%ee);AD-H(n-hexane 100%,0.8mL/min):tR=10.5min, tR=11.0min(major).[α]D 27=38.7(c 1.00,CHCl3).1H NMR(400MHz,CDCl3): 7.61-7.55(m,2H),7.44-7.41(m,3H),7.38-7.33(m,3H),7.27-7.26(m,2H),7.03(d, J=8.0Hz,2H),6.98(d,J=8.2Hz,2H),6.05(td,J=57.2,4.4Hz,1H),5.07(dd,J= 5.0,2.4Hz,1H),3.33-3.18(m,1H),2.28(s,3H).19F NMR(377MHz,CDCl3): -107.57/-109.43(m,2F).13C NMR(101MHz,CDCl3):136.3,135.9,135.7,131.7(t, J=6.1Hz),130.4,130.1,129.5,129.5,128.3,128.1,118.6(t,J=244.4Hz),41.0(t, J=22.2Hz),21.1.HRMS(ESI,m/z):calcd for C21 H20F2NaSi+[M+Na]+:361.1195, found:361.1192.
实施例3
在氩气氛围下,在真空封管中加入Ni(COD)2(5mol%),L1(5mol%),甲苯(1.5mL),室温搅拌30分钟,加入B(C6F5)3(5mol%),室温搅拌30分钟,加入化合物2a(0.04mmol,1mol/L,48μL),室温搅拌10分钟,加入化合物2a(0.36mmol, 1mol/L,0.43mL),4A分子筛(50mg),对甲氧基苯胺(10mol%)和化合物1c(0.2 mmol)。置于30℃油浴搅拌24h,将反应混合物通过硅藻土过滤,二氯甲烷及乙酸乙酯洗脱,经过减压蒸馏浓缩后,柱层析(PE:EA=100:1)纯化得到目标产物3c。无色油状物(产率99%/92%ee);OD-H(n-hexane/i-PrOH=98/2,1.0mL/min):tR= 5.0min(major),tR=5.3min.[α]D 27=52.4(c 1.00,CHCl3).1H NMR(400MHz, CDCl3):7.61-7.55(m,2H),7.49-7.43(m,1H),7.42-7.36(m,5H),7.34-7.26(m,2H), 7.21-7.17(m,2H),7.01(d,J=8.4Hz,2H),6.05(td,J=57.0,4.0Hz,1H),5.06(dd, J=5.4,2.4Hz,1H),3.34-3.18(m,1H).19F NMR(377MHz,CDCl3):-108.02/ -109.87(m,2F).13C NMR(101MHz,CDCl3):135.8,135.7,133.4(t,J=5.1Hz), 132.7,131.1,130.9,130.6,130.4,128.9,128.5,128.2,118.0(t,J=243.4Hz),41.0(t, J=21.2Hz).HRMS(ESI,m/z):calcd for C20H17ClF2NaSi+[M+Na]+:381.0648, found:381.0647.
实施例4
在氩气氛围下,在真空封管中加入Ni(COD)2(5mol%),L1(5mol%),甲苯(1.5mL),室温搅拌30分钟,加入B(C6F5)3(5mol%),室温搅拌30分钟,加入化合物2a(0.04mmol,1mol/L,48μL),室温搅拌10分钟,加入化合物2a(0.36mmol, 1mol/L,0.43mL),4A分子筛(50mg),对甲氧基苯胺(10mol%)和化合物1d(0.2 mmol)。置于30℃油浴搅拌24h,将反应混合物通过硅藻土过滤,二氯甲烷及乙酸乙酯洗脱,经过减压蒸馏浓缩后,柱层析(PE:EA=100:1)纯化得到目标产物3d。白色固体(m.p.56-57℃)(产率99%/95%ee);AD-H(n-hexane100%,0.8mL/min): tR=17.4min,tR=19.3min(major).[α]D 27=38.9(c 1.00,CHCl3).1HNMR(400 MHz,CDCl3):7.80-7.74(m,1H),7.72-7.64(m,2H),7.62-7.57(m,2H),7.53(s,1H), 7.47-7.40(m,5H),7.40-7.32(m,3H),7.28-7.22(m,2H),7.21-7.18(m,1H),6.17(td,J=57.0,4.2Hz,1H),5.15(d,J=2.4Hz,1H),3.55-3.37(m,1H).19F NMR(377 MHz,CDCl3):-107.29/-109.24(m,2F).13C NMR(101MHz,CDCl3):135.9,135.7, 133.6,132.5(t,J=4.0Hz),132.3,131.4,131.3,130.5,130.3,128.4,128.2,128.1, 128.0,127.8,127.7,126.3,125.8,118.5(t,J=243.4Hz),41.6(t,J=22.2Hz). HRMS(ESI,m/z):calcd forC24H20F2NaSi+[M+Na]+:397.1195,found:397.1174.
实施例5
在氩气氛围下,在真空封管中加入Ni(COD)2(5mol%),L1(5mol%),甲苯(1.5mL),室温搅拌30分钟,加入B(C6F5)3(5mol%),室温搅拌30分钟,加入化合物2a(0.04mmol,1mol/L,48μL),室温搅拌10分钟,加入化合物2a(0.36mmol, 1mol/L,0.43mL),4A分子筛(50mg),对甲氧基苯胺(10mol%)和化合物1e(0.2 mmol)。置于30℃油浴搅拌24h,将反应混合物通过硅藻土过滤,二氯甲烷及乙酸乙酯洗脱,经过减压蒸馏浓缩后,柱层析(PE:EA=100:1)纯化得到目标产物3e。白色固体(m.p.54-55℃)(产率99%/90%ee);PC3(CH3CN/H2O=70/30,0.7mL/min): tR=14.1min(major),tR=18.8min.[α]D 27=35.5(c 1.00,CHCl3).1H NMR(400 MHz,CDCl3):7.63-7.54(m,4H),7.47-7.40(m,4H),7.40-7.33(m,3H),7.28-7.24(m, 2H),7.17-7.11(m,1H),7.12-7.06(m,2H),6.15(td,J=57.2,4.2Hz,1H),5.17-5.12 (m,1H),3.89(s,3H),3.49-3.34(m,1H).19F NMR(377MHz,CDCl3):-107.38 /-109.29(m,2F).13C NMR(101MHz,CDCl3):157.6,135.8,135.6,134.4,133.3, 131.4,131.32,130.30,130.1,129.9,129.8(t,J=5.1Hz),129.0,128.2,128.0(t,J= 243.3Hz),127.1,119.0,118.5,116.1,105.5,55.3,41.2(t,J=21.2Hz).HRMS(ESI, m/z):calcd forC25H22F2NaOSi+[M+Na]+:427.1300,found:427.1304.
实施例6
在氩气氛围下,在真空封管中加入Ni(COD)2(5mol%),L1(5mol%),甲苯(1.5mL),室温搅拌30分钟,加入B(C6F5)3(5mol%),室温搅拌30分钟,加入化合物2a(0.04mmol,1mol/L,48μL),室温搅拌10分钟,加入化合物2a(0.36mmol,1mol/L,0.43mL),4A分子筛(50mg),对甲氧基苯胺(10mol%)和化合物1f(0.2 mmol)。置于30℃油浴搅拌24h,将反应混合物通过硅藻土过滤,二氯甲烷及乙酸乙酯洗脱,经过减压蒸馏浓缩后,柱层析(PE:EA=100:1)纯化得到目标产物3f。无色油状物(产率99%/92%ee);AD-H(n-hexane 100%,0.8mL/min):tR=10.4min, tR=11.0min(major).[α]D 27=56.0(c 0.50,CHCl3).1H NMR(600MHz,CDCl3): 7.59-7.55(m,2H),7.45(t,J=7.5Hz,1H),7.41-7.36(m,5H),7.31-7.29(m,2H), 7.22-7.21(m,1H),6.90(d,J=1.9Hz,1H),6.82(d,J=4.8Hz,1H),6.04(td,J=57.2,3.8Hz,1H),5.07(d,J=2.6Hz,1H),3.52-3.42(m,1H).19F NMR(377MHz, CDCl3):-109.19/-109.46(m,2F).13C NMR(151MHz,CDCl3):135.8,135.7,133.9 (t,J=4.5Hz),131.4,131.3,130.5,130.3,128.9,128.4,128.1,125.7,122.5,117.9(t, J=243.1Hz),36.5(t,J=21.1Hz).HRMS(ESI,m/z):calcd for C18H17F2SSi+[M+ H]+:331.0783,found:331.0781.
实施例7
在氩气氛围下,在真空封管中加入Ni(COD)2(5mol%),L1(5mol%),甲苯(1.5mL),室温搅拌30分钟,加入B(C6F5)3(5mol%),室温搅拌30分钟,加入化合物2a(0.04mmol,1mol/L,48μL),室温搅拌10分钟,加入化合物2a(0.36mmol, 1mol/L,0.43mL),4A分子筛(50mg),对甲氧基苯胺(10mol%)和化合物1g(0.2 mmol)。置于30℃油浴搅拌24h,将反应混合物通过硅藻土过滤,二氯甲烷及乙酸乙酯洗脱,经过减压蒸馏浓缩后,柱层析(PE:EA=100:1)纯化得到目标产物3g。白色固体(m.p.78-80℃)(产率99%/92%ee);NY(2)-RH 5u(CH3CN/H2O=70/30,0.7 mL/min):tR=7.4min(major),tR=8.9min.[α]D 27=35.2(c 1.00,CHCl3).1H NMR (400MHz,CDCl3):7.64-7.58(m,2H),7.58-7.53(m,2H),7.48-7.39(m,8H),7.37- 7.34(m,2H),7.33-7.24(m,3H),7.15(d,J=8.2Hz,2H),6.12(td,J=57.0,4.4Hz,1H),5.11(dd,J=5.2,2.4Hz,1H),3.41-3.27(m,1H).19F NMR(565MHz,CDCl3): -107.74/-109.13(m,2F).13C NMR(151MHz,CDCl3):140.7,139.5,135.9,135.7, 134.5,134.0(t,J=4.5Hz),131.4,131.3,130.5,130.2,130.0,128.9,128.4,128.1, 127.4,127.1,118.4,(t,J=243.1Hz),41.1(t,J=21.1Hz).HRMS(ESI,m/z):calcd for C26H22F2NaSi+[M+Na]+:423.1351,found:423.1345.
实施例8
在氩气氛围下,在真空封管中加入Ni(COD)2(5mol%),L1(5mol%),甲苯(1.5mL),室温搅拌30分钟,加入B(C6F5)3(5mol%),室温搅拌30分钟,加入化合物2a(0.04mmol,1mol/L,48μL),室温搅拌10分钟,加入化合物2a(0.36mmol, 1mol/L,0.43mL),4A分子筛(50mg),对甲氧基苯胺(10mol%)和化合物1h(0.2 mmol)。置于30℃油浴搅拌24h,将反应混合物通过硅藻土过滤,二氯甲烷及乙酸乙酯洗脱,经过减压蒸馏浓缩后,柱层析(PE:EA=100:1)纯化得到目标产物3h。白色固体(m.p.73-75℃)(产率99%/93%ee);NY(2)-RH 5u(CH3CN/H2O=80/20,0.7 mL/min):tR=7.6min(major),tR=11.0min.[α]D 27=29.7(c1.00,CHCl3).1H NMR (400MHz,CDCl3):7.63-7.55(m,2H),7.50-7.46(m,2H),7.45-7.41(m,4H), 7.41-7.32(m,4H),7.31-7.31(m,2H),7.12(d,J=8.2Hz,2H),6.97-6.92(m,2H),6.10(td,J=57.2,4.4Hz,1H),5.10(dd,J=5.2,2.4Hz,1H),3.82(s,3H),3.39-3.25 (m,1H).19F NMR(377MHz,CDCl3):-107.75/-109.13(m,2F).13C NMR(101MHz, CDCl3):159.3,139.2,135.9,135.8,133.3(t,J=6.1Hz),131.5,131.4,130.4,130.2, 130.0,128.4,128.1,128.1,127.0,120.9,118.5(t,J=243.4Hz),114.4,55.5,41.1(t,J =21.2Hz).HRMS(ESI,m/z):calcd for C27H24F2NaOSi+[M+Na]+:453.14 57, found:453.1456.
实施例10
在氩气氛围下,在真空封管中加入Ni(COD)2(5mol%),L1(5mol%),甲苯(1.5mL),室温搅拌30分钟,加入B(C6F5)3(5mol%),室温搅拌30分钟,加入化合物2a(0.04mmol,1mol/L,48μL),室温搅拌10分钟,加入化合物2a(0.36mmol, 1mol/L,0.43mL),4A分子筛(50mg),对甲氧基苯胺(10mol%)和化合物1i(0.2 mmol)。置于30℃油浴搅拌24h,将反应混合物通过硅藻土过滤,二氯甲烷及乙酸乙酯洗脱,经过减压蒸馏浓缩后,柱层析(PE:EA=100:1)纯化得到目标产物3i。白色固体(m.p.63-64℃)(产率80%/95%ee);NY(2)-RH 5u(CH3CN/H2O=80/20,0.7 mL/min):tR=8.8min(major),tR=11.5min.[α]D 27=32.0(c1.00,CHCl3).1H NMR (400MHz,CDCl3):8.08(d,J=8.4Hz,2H),7.64-7.59(m,4H),7.50-7.42(m,5H), 7.42-7.33(m,3H),7.31-7.27(m,2H),7.18(d,J=8.2Hz,2H),6.12(td,J=57.0,4.2 Hz,1H),5.11(d,J=2.6Hz,1H),3.92(s,3H),3.45-3.28(m,1H).19F NMR(377MHz,CDCl3):-107.63/-109.45(m,2F).13C NMR(101MHz,CDCl3):167.1,145.2, 138.3,135.9,135.7,135.1(t,J=5.1Hz),131.2,131.2,130.5,130.3,130.2,130.2, 129.0,128.4,128.2,127.5,126.9,118.3(t,J=243.4Hz),52.2,41.3(t,J=21.2Hz). HRMS(ESI,m/z):calcd for C28H24F2NaO2Si+[M+Na]+:481.1406,found: 481.1401.
实施例10
在氩气氛围下,在真空封管中加入Ni(COD)2(5mol%),L1(5mol%),甲苯(1.5mL),室温搅拌30分钟,加入B(C6F5)3(5mol%),室温搅拌30分钟,加入化合物2a(0.04mmol,1mol/L,48μL),室温搅拌10分钟,加入化合物2a(0.36mmol,1 mol/L,0.43mL),4A分子筛(50mg),对甲氧基苯胺(10mol%)和化合物1j(0.2 mmol)。置于30℃油浴搅拌24h,将反应混合物通过硅藻土过滤,二氯甲烷及乙酸乙酯洗脱,经过减压蒸馏浓缩后,柱层析(PE:EA=100:1)纯化得到目标产物3j。无色油状物(产率99%/90%ee);PA2(CH3CN/H2O=70/30,0.7mL/min):tR=13.1 min(major),tR=14.8min.[α]D 27=31.4(c 1.00,CHCl3).1H NMR(400MHz, CDCl3):7.63(d,J=7.2Hz,2H),7.55-7.47(m,4H),7.47-7.42(m,1H),7.42-7.36(m, 3H),7.35-7.29(m,4H),7.25-7.21(m,1H),7.10(d,J=3.6Hz,1H),6.73(d,J=3.6 Hz,1H),6.02(td,J=57.0,3.6Hz,1H),5.17(d,J=2.6Hz,1H),3.63-3.48(m,1H). 19F NMR(377MHz,CDCl3):-108.91/-110.70(m,2F).13C NMR(101MHz,CDCl3): 143.5,135.8,135.7,135.3(t,J=5.1Hz),134.4,131.1,130.9,130.6,130.4,129.0, 128.5,128.2,128.2,127.5,125.7,123.3,117.2(t,J=245.4Hz),36.3(t,J=22.2Hz). HRMS(ESI,m/z):calcdfor C24H20F2NaSSi+[M+Na]+:429.0 915,found:429.0910.
实施例11
在氩气氛围下,在真空封管中加入Ni(COD)2(5mol%),L1(5mol%),甲苯(1.5mL),室温搅拌30分钟,加入B(C6F5)3(5mol%),室温搅拌30分钟,加入化合物2a(0.04mmol,1mol/L,48μL),室温搅拌10分钟,加入化合物2a(0.36mmol, 1mol/L,0.43mL),4A分子筛(50mg),对甲氧基苯胺(10mol%)和化合物1k(0.2 mmol)。置于30℃油浴搅拌24h,将反应混合物通过硅藻土过滤,二氯甲烷及乙酸乙酯洗脱,经过减压蒸馏浓缩后,柱层析(PE:EA=100:1)纯化得到目标产物3k。无色油状物(产率99%/91%ee);PC3(CH3CN/H2O=70/30,0.7mL/min):tR=26.8 min(major),tR=43.9min.[α]D 27=81.3(c 0.30,CHCl3).1H NMR(600MHz, CDCl3):7.64(d,J=7.2Hz,2H),7.61-7.58(m,4H),7.50(d,J=7.2Hz,2H),7.48-7.44(m,1H),7.45-7.38(m,3H),7.33(t,J=7.2Hz,2H),7.19(d,J=3.2Hz, 1H),6.77(d,J=3.2Hz,1H),6.03(td,J=57.2,3.8Hz,1H),5.16(s,1H),3.63-3.53 (m,1H).19F NMR(377MHz,CDCl3):-62.52(s,3F),-109.12/-111.10(m,2F).13C NMR(151MHz,CDCl3):141.6,137.7,137.0(t,J=4.5Hz),135.8,135.6,134.5, 130.8,130.6,130.6,129.2(q,J=32.5Hz)128.5,128.4,128.3,126.0(q,J=3.6Hz), 125.7,124.7,124.3(q,J=272.0Hz),117.0(t,J=244.6Hz),36.3(t,J=22.7Hz). HRMS(ESI,m/z):calcd for C25H19F5NaSSi+[M+Na]+:497.0789,found:497.0790.
实施例12
在氩气氛围下,在真空封管中加入Ni(COD)2(5mol%),L1(5mol%),甲苯(1.5mL),室温搅拌30分钟,加入B(C6F5)3(5mol%),室温搅拌30分钟,加入化合物2b(0.04mmol,1mol/L,48μL),室温搅拌10分钟,加入化合物2b(0.36mmol, 1mol/L,0.43mL),4A分子筛(50mg),对甲氧基苯胺(10mol%)和化合物1a(0.2 mmol)。置于30℃油浴搅拌24h,将反应混合物通过硅藻土过滤,二氯甲烷及乙酸乙酯洗脱,经过减压蒸馏浓缩后,柱层析(PE:EA=100:1)纯化得到目标产物3ab。无色油状物(产率93%/91%ee);NY(2)-RH 5u(CH3CN/H2O=65/35,0.7mL/min):tR=16.8min(major),tR=18.8min.[α]D 27=22.0(c 1.00,CHCl3).1HNMR(400MHz, CDCl3):7.48-7.45(m,2H),7.31-7.26(m,2H),7.25-7.23(m,2H),7.00(d,J=8.3Hz, 2H),6.93-6.90(m,2H),6.82(d,J=8.6Hz,2H),6.06(td,J=57.2,4.6Hz,1H),5.03(dd,J=5.0,2.4Hz,1H),3.81(s,3H),3.77(s,3H),3.31-3.09(m,1H),1.29(s,9H). 19F NMR(377MHz,CDCl3):-107.61/-109.46(m,2F).13C NMR(151MHz,CDCl3): 161.4,161.2,149.5,137.4,137.2,132.0(t,J=4.5Hz),129.2,125.6,122.7,122.6, 118.8(t,J=243.1Hz),114.1,113.8,55.2,55.1,41.1(t,J=21.1Hz),34.5,31.5. HRMS(ESI,m/z):calcd forC26H30F2NaO2Si+[M+Na]+:463.1875,found:463. 1880.
实施例13
在氩气氛围下,在真空封管中加入Ni(COD)2(5mol%),L1(5mol%),甲苯(1.5mL),室温搅拌30分钟,加入B(C6F5)3(5mol%),室温搅拌30分钟,加入化合物2c(0.04mmol,1mol/L,48μL),室温搅拌10分钟,加入化合物2c(0.36mmol, 1mol/L,0.43mL),4A分子筛(50mg),对甲氧基苯胺(10mol%)和化合物1a(0.2 mmol)。置于30℃油浴搅拌24h,将反应混合物通过硅藻土过滤,二氯甲烷及乙酸乙酯洗脱,经过减压蒸馏浓缩后,柱层析(PE:EA=100:1)纯化得到目标产物3ac。无色油状物(产率94%/95%ee);NY(2)-RH 5u(CH3CN/H2O=80/20,0.7mL/min):tR=7.1min(major),tR=8.1min.[α]D 27=28.5(c 1.00,CHCl3).1H NMR(400MHz, CDCl3):7.40-7.33(m,2H),7.29-7.23(m,4H),7.19-7.12(m,3H),7.08(s,1H),7.02 (d,J=8.4Hz,2H),6.07(td,J=57.2,4.4Hz,1H),5.03(s,1H),3.35-3.15(m,1H),2.33(s,3H),2.23(s,3H),1.31-1.27(s,9H).19F NMR(565MHz,CDCl3):-107.92/ -109.16(m,2F).13C NMR(151MHz,CDCl3):149.5,137.6,137.3,136.5,136.4, 132.9,132.7,131.8(t,J=4.5Hz),131.5,131.5,131.1,130.8,129.3,128.2,127.9, 125.6,118.6(t,J=241.6Hz),40.8(t,J=21.1Hz),34.5,31.5,21.6,21.5.HRMS (ESI,m/z):calcd forC26H30F2NaSi+[M+Na]+:431.1977,found:431.1976.
实施例14
在氩气氛围下,在真空封管中加入Ni(COD)2(5mol%),L1(5mol%),甲基叔丁基醚(1.5mL),室温搅拌30分钟,加入B(C6F5)3(5mol%),室温搅拌30分钟,加入化合物2a(0.04mmol,1mol/L,48μL),室温搅拌10分钟,加入化合物2a (0.36mmol,1mol/L,0.43mL),4A分子筛(50mg),对甲氧基苯胺(10mol%)和化合物1l(0.2mmol)。置于30℃油浴搅拌24h,将反应混合物通过硅藻土过滤,二氯甲烷及乙酸乙酯洗脱,经过减压蒸馏浓缩后,柱层析(PE:EA=100:1)纯化得到目标产物3l。无色油状物(产率65%/87%ee);OD-H(n-hexane/i-PrOH=99/1,1.0 mL/min):tR=6.0min,tR=7.8min(major).[α]D 27=51.5(c 1.00,CHCl3).1H NMR (400MHz,CDCl3):7.69-5.69(m,4H),7.45-7.36(m,6H),7.28-7.20(m,5H),6.35-6.13(m,2H),6.03(td,J=57.2,3.8Hz,1H),5.03(d,J=2.2Hz,1H),3.06-2.88(m, 1H).19FNMR(377MHz,CDCl3):-108.90/-112.15(m,2F).13C NMR(101MHz, CDCl3):137.3,135.9,135.8,133.4,131.3,131.1,130.5,130.4,128.7,128.4,128.3, 127.5,126.2,121.72(t,J=6.1Hz),117.8(t,J=243.4Hz),38.6(t,J=21.2Hz). HRMS(ESI,m/z):calcd forC27H24F2NaSi+[M+Na]+:373.1195,found:373.1184.
以上所述仅为本发明的优选实施例,不能认定本发明的具体实施只局限于这些说明。对于本发明所属技术领域的相关技术人员来说,在不脱离本发明构思的前提下,还可以做出若干简单推演和替换,其中所作的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
Claims (7)
2.根据权利要求1所述手性α-二氟甲基硅烷类化合物3的合成方法,其特征在于:所述有机溶剂选自THF、DMA、甲基叔丁基醚、甲苯、二氧六环。
3.根据权利要求2所述手性α-二氟甲基硅烷类化合物3的合成方法,其特征在于:所述有机溶剂选自甲苯。
4.根据权利要求1所述手性α-二氟甲基硅烷类化合物3的合成方法,其特征在于:所述偕二氟烯烃1、二苯基硅烷2、Ni(COD)2、手性配体L、B(C6F5)3及对甲氧基苯胺摩尔比为1:1-2:0.01-0.05:0.01-0.05:0.02-0.05:0.05-0.1。
5.根据权利要求1所述手性α-二氟甲基硅烷类化合物3的合成方法,其特征在于:每mmol偕二氟烯烃1中加入250mg 4A分子筛。
6.根据权利要求1-5任意一项所述手性α-二氟甲基硅烷类化合物3的合成方法,其特征在于:反应温度为20-40℃。
7.根据权利要求6所述手性α-二氟甲基硅烷类化合物3的合成方法,其特征在于:所述反应在惰性气体保护下进行,惰性气体为氩气。
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