一类固体有机硅锌试剂及其制备方法及应用

1.本发明属于合成有机化学技术领域，尤其是指一类固体有机硅锌试剂及其制备方法及应用。


背景技术：

2.碳硅键的构建是有机合成化学、材料合成化学等领域的一个具有挑战的研究方向。现有的有机硅试剂主要包括硅氢试剂、硅硼试剂以及传统的硅锌试剂。其中硅氢试剂主要用于末端烯烃的硅氢化反应，用于构建一个碳硅键；极性反转的有机硅硼试剂用途相对较广，但是合成不易，需要通过贵金属铱或铑催化剂来合成；传统的硅锌试剂对空气和水非常敏感，需要在-30℃下低温保存，储存不易，碱性强、且亲核性过高，副产物多。基于上述原因，提高试剂稳定性和调控反应活性是开发新型有机硅试剂的两个亟需解决的问题。本发明基于阴离子配位调控的策略，通过筛选不同阴离子从而实现对硅锌试剂的物理和化学性质的调控，既提高稳定性又改善反应性。


技术实现要素：

3.为解决上述技术问题，本发明提供了一类固体有机硅锌试剂及其制备方法及应用；本发明通过阴离子配位调控策略设计、制备一类对空气和水具有良好稳定性的新型固体有机硅锌试剂，并实现对反应性的有效调控。为有机合成化学和材料合成化学提供一类稳定性和反应活性良好的新型有机硅合成子，从而解决传统硅锌试剂稳定性差，保存不易，反应性不可控等方面的挑战。
4.本发明第一个目的是提供一类新型固体有机硅锌试剂，所述有机硅锌试剂结构式：
5.r3si-znopiv
·
licl；
6.其中，r为取代芳基、链式烷基、环状烷基、叔丁氧基、二乙基氨基、环己二醚和环庚二醚中的一种或多种。
7.本发明第二个目的是提供一种新型固体有机硅锌试剂的制备方法，包括以下步骤：有机溶剂中，在催化剂作用下，有机硅烷与金属锂或锂试剂混合反应得到有机硅锂试剂，并使用zn(opiv)2将所得有机硅锂试剂进行转金属化反应。
8.在本发明的一个实施例中，所述催化剂选自奈或奈的衍生物、蒽或蒽的衍生物、六甲基磷酰三胺和多环稠合芳烃中的一种或多种。
9.在本发明的一个实施例中，所述奈的衍生物为烷基、甲氧基、醚基、n，n-二甲基取代的萘或叔丁基取代的联苯；所述蒽的衍生物为烷基、甲氧基、醚基或n，n-二甲基取代的蒽。
10.在本发明的一个实施例中，所述有机硅烷选自芳基氯硅烷、六甲基二硅烷、链状烷基取代氯硅烷、环状烷基取代氯硅烷、叔丁氧基取代氯硅烷、二乙基氨基取代氯硅烷、环己二醚取代氯硅烷和环庚二醚取代氯硅烷中的一种或多种。
11.在本发明的一个实施例中，所述锂试剂包括甲基锂试剂或/和丁基锂试剂。
12.在本发明的一个实施例中，所述有机溶剂为乙醚、甲苯、2-甲基呋喃、四氢呋喃、叔丁基甲基醚和1,2-二氧六环中的一种或多种。
13.在本发明的一个实施例中，所述催化剂相对有机硅烷的用量为1-20mol％。
14.在本发明的一个实施例中，制备有机硅锂试剂的反应条件为：反应温度0至-78℃，反应时间10min-24h。进一步的，反应温度为0至-18℃，反应时间15min-8h。
15.本发明的第三个目的是提供所述的有机硅锌试剂在交叉偶联反应过渡金属镍催化非活化烯烃与碘代烷烃或溴苄的烯烃双官能团化的应用。
16.在本发明的一个实施例中，所述交叉偶联反应为过渡金属镍催化非活化烯烃与碘代烷烃或溴苄的烯烃双官能团化反应。
17.本发明的上述技术方案相比现有技术具有以下优点：
18.本发明所述的固体硅锌试剂的设计与制备方法是首次报道，且在稳定性和反应性方面都通过阴离子配位实现了正向调控。在有机合成、硅材料合成中碳硅键的构建、以及药物化学领域中新药发现等方面具有良好的应用潜力和前景。本发明所述新型固体硅锌试剂通过阴离子配位调节，可以实现硅锌试剂理化性质的有效调控。一方面，通过大位阻阴离子与锌的离子键结合阻隔空气中的水和其他敏感成分，实现对硅锌试剂物理稳定性的调控；另一方面，通过改变阴离子配位，影响硅中心与锌中心的键长，从而实现硅锌试剂反应活性的调控，此外，特戊酸阴离子可以协助硅锌试剂与过渡金属催化剂之间的转金属化反应，从而调节硅锌试剂在催化合成中的反应活性。例如，在本技术书中通过特戊酸配位的硅锌试剂在过渡金属催化的烯烃双官能团化反应中表现出特殊且高效的反应性，以高化学选择性实现非活化烯烃的双官能团化。
附图说明
19.为了使本发明的内容更容易被清楚的理解，下面根据本发明的具体实施例并结合附图，对本发明作进一步详细的说明，其中
20.图1是本发明实施例1和实施例2新型硅锌试剂的制备与应用，其中r为烷基，如甲基或乙基。
21.图2是本发明实施例1和实施例2固体硅锌试剂制备的两种方法。
22.图3是本发明固体硅锌试剂的反应性。
23.图4是本发明应用例中硅锌试剂的反应性考察结果。
具体实施方式
24.下面结合附图和具体实施例对本发明作进一步说明，以使本领域的技术人员可以更好地理解本发明并能予以实施，但所举实施例不作为对本发明的限定。
25.实施例1
26.在50ml干燥和充满惰性气体(n2)的双颈圆底烧瓶中加入萘(64mg，0.5mmol)、锂碎屑(174mg，25mmol)和干燥的thf(10.0ml)，于室温下搅拌1小时至变成深绿色溶液。降温至0℃，称取苯基二甲基氯硅烷(10mmol，1.7g)并滴加至圆底烧瓶中，反应混合液在0℃下持续反应8小时。根据kofron的方法，用碘滴定硅锂试剂并计算浓度，按照硅锂试剂浓度的1.2倍
加入zn(opiv)2固体，并将反应混合物在室温搅拌15分钟。使用knochel方法滴定硅锌试剂(通常形成约0.5m溶液)，真空下除去溶剂残留即可得到相应的固体硅锌试剂(收率58％)。具体反应过程如图2所示。
27.实施例2
28.在50ml干燥和充满惰性气体(n2)的双颈圆底烧瓶中加入萘(64mg，0.5mmol)、锂碎屑(174mg，25mmol)和干燥的thf(10.0ml)，于室温下搅拌1小时至变成深绿色溶液。降温至0℃，称取二苯基甲基氯硅烷(10mmol，2.32g)并滴加至圆底烧瓶中，反应混合液在0℃下持续反应8小时。根据kofron的方法，用碘滴定硅锂试剂并计算浓度，按照硅锂试剂浓度的1.2倍加入zn(opiv)2固体，并将反应混合物在室温搅拌15分钟。使用knochel方法滴定硅锌试剂(通常形成约0.5m溶液)，真空下除去溶剂残留即可得到相应的固体硅锌试剂(收率55％)。
29.实施例3
30.在30ml干燥和充满惰性气体(n2)的两颈圆底烧瓶中加入六甲基二硅烷(1.0ml，4.88mmol)、六甲基磷酰三胺(hmpa)(2.0ml，11.4mmol)，降温至-78℃冷却。向反应液中加入8ml干燥的thf，以及meli(1.07m/et2o，3.65ml，3.91mmol)。逐渐升温至0℃搅拌15分钟后。根据kofron的方法，用碘滴定硅锂试剂并计算浓度，按照硅锂试剂浓度的1.2倍加入zn(opiv)2固体，并将反应混合物在室温搅拌15分钟。使用knochel方法滴定三甲基硅锌试剂(通常形成约0.5m溶液)。在六甲基磷酰三胺(hmpa)存在下，通过六甲基二硅烷与甲基锂试剂的交换法制备得到三甲基硅锂试剂，并对上述制备得到的硅锂试剂通过knochel方法进行滴定并确定浓度，真空下除去溶剂残留即可得到相应的固体硅锌试剂(收率56％)。
31.应用例
32.将实施例中所得与反应混合，得到具体反应条件见图4，图中aq指代的是8-氨基喹啉；r表示的就是上述实施例3中制备的六种固体硅金属试剂，包括芳基和烷基；n的范围是1和2。反应所得产物见图4，由图4可知，使用本发明所得固体硅锌试剂在过渡金属镍催化非活化烯烃与碘代烷烃或溴苄的烯烃双官能团化反应中，产物具有较高的收率。
33.为了进一步测试上述新型硅锌试剂的反应性，设计了本发明固体硅锌试剂在过渡金属镍催化非活化烯烃与碘代烷烃或溴苄的烯烃双官能团化反应。通过对催化体系的反应条件筛选后，选取烯烃的硅基-苄基化反应为例进行系统的反应动力学监测，实验结果表明该类固体硅锌试剂与传统的硅锌试剂相比，在反应性方面表现出了明显的优越性，以高转化率得到目标产物，具体如图3所示，所得化合物5-化合物65核磁表征结果如下所示。
34.化合物5-化合物65的核磁表征数据：
35.3-{[dimethyl(phenyl)silyl]methyl}-n-(quinolin-8-yl)hexanamide(5)
[0036]1h-nmr(400mhz,cdcl3):δ＝9.71(s,1h),8.82
–
8.74(m,2h),8.15(dd,j＝8.3,1.7hz,1h),7.55
–
7.51(m,3h),7.48
–
7.43(m,2h),7.31
–
7.28(m,3h),2.48(dd,j＝14.3,7.1hz,1h),2.39(dd,j＝14.3,6.6hz,1h),2.27(t,j＝6.7hz,1h),1.39
–
1.25(m,5h),0.96(d,j＝6.7hz,2h),0.81(td,j＝5.6,4.5,2.4hz,3h),0.34(d,j＝1.0hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.5,148.2,139.8,138.5,136.5,134.7,133.7,128.9,128.1,127.9,127.6,121.7,121.4,116.5,46.1,39.2,32.2,21.3,19.7,14.3,-1.9,-2.0.hr-ms
(ei)m/z calcd for c
24h30
n2osi[m h

]391.2201,found 391.2200.
[0037]
3-benzyl-4-[dimethyl(phenyl)silyl]-n-(quinolin-8-yl)butanamide(6)
[0038]1h-nmr(400mhz,cdcl3):δ＝9.66(s,1h),8.84
–
8.68(m,2h),8.14(dd,j＝8.2,1.7hz,1h),7.54
–
7.49(m,3h),7.49
–
7.39(m,2h),7.31
–
7.29(m,3h),7.24
–
7.21(m,2h),7.17
–
7.09(m,3h),2.76
–
2.58(m,2h),2.53(p,j＝6.6hz,1h),2.39(qd,j＝14.6,6.4hz,2h),1.01(qd,j＝14.9,6.5hz,2h),0.34(s,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.2,148.1,139.5,138.5,137.4,136.5,135.5,134.7,133.7,129.4,129.1,129.0,128.1,127.9,127.6,121.7,121.4,116.5,45.0,43.0,34.3,21.1,-1.9.hr-ms(ei)m/z calcd for c
28h30
n2osi[m h

]439.2201,found 439.2204.
[0039]
4-[dimethyl(phenyl)silyl]-3-methyl-n-(quinolin-8-yl)butanamide(7)
[0040]1h-nmr(400mhz,cdcl3):δ＝9.73(s,1h),8.85
–
8.72(m,2h),8.15(dd,j＝8.3,1.7hz,1h),7.55
–
7.51(m,3h),7.50
–
7.41(m,2h),7.34
–
7.27(m,3h),2.55
–
2.44(m,1h),2.43
–
2.31(m,2h),1.11
–
0.84(m,5h),0.34(d,j＝1.2hz,6h.
13
c-nmr(100mhz,cdcl3):δ＝171.3,148.2,139.7,138.5,136.5,134.7,133.7,128.9,128.1,127.9,127.6,121.7,121.5,116.5,49.5,28.0,24.3,23.1,-1.8,-2.0.hr-ms(ei)m/z calcd for c
22h26
n2osi[m h

]363.1888,found 363.1885.
[0041]
3-{[dimethyl(phenyl)silyl]methyl}-n-(quinolin-8-yl)pentanamide(8)
[0042]1h-nmr(400mhz,cdcl3):δ＝9.73(s,1h),8.86
–
8.72(m,2h),8.15(dd,j＝8.3,1.7hz,1h),7.56
–
7.42(m,5h),7.30(dd,j＝4.8,1.8hz,3h),2.54
–
2.34(m,2h),2.21(hept,j＝6.6hz,1h),1.42(qd,j＝7.4,5.9hz,2h),0.95(dd,j＝6.8,2.2hz,2h),0.88(t,j＝7.4hz,3h),0.34(s,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.5,148.2,139.8,138.5,136.5,134.7,133.6,128.9,128.1,127.9,127.6,121.7,121.4,116.5,45.6,33.8,29.4,20.8,10.9,-1.9,-2.1.hr-ms(ei)m/z calcd for c
23h28
n2osi[m h

]377.2024,found 377.2021.
[0043]
3-{[dimethyl(phenyl)silyl]methyl}-n-(quinolin-8-yl)heptanamide(9)
[0044]1h-nmr(400mhz,cdcl3):δ＝9.72(s,1h),8.87
–
8.72(m,2h),8.15(dd,j＝8.3,1.7hz,1h),7.55
–
7.51(m,3h),7.50
–
7.42(m,2h),7.33
–
7.27(m,3h),2.49(dd,j＝14.3,7.0hz,1h),2.39(dd,j＝14.3,6.7hz,1h),2.25(p,j＝6.5hz,1h),1.42
–
1.33(m,2h),1.32
–
1.23(m,2h),1.23
–
1.14(m,2h),0.96(d,j＝6.8hz,2h),0.82(t,j＝7.2hz,3h),0.34(d,j＝2.1hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.5,148.2,139.8,138.5,136.5,134.7,133.7,128.9,128.1,127.9,127.6,121.7,121.4,116.5,46.1,36.6,32.4,28.8,23.0,21.4,14.2,-2.0,-2.0.hr-ms(ei)m/z calcd for c
25h32
n2osi[m h

]405.2357,found 405.2355.
[0045]
3-{[dimethyl(phenyl)silyl]methyl}-6-methyl-n-(quinolin-8-yl)heptanamide(10)
[0046]1h-nmr(400mhz,cdcl3):δ＝9.72(s,1h),8.83
–
8.73(m,2h),8.16(dd,j＝8.3,1.7hz,1h),7.55
–
7.51(m,3h),7.50
–
7.41(m,2h),7.29(dd,j＝4.9,1.8hz,3h),2.55
–
2.32(m,2h),2.23(p,j＝6.6hz,1h),1.47
–
1.30(m,3h),1.25
–
1.09(m,2h),0.99
–
0.90(m,2h),0.78(d,j＝6.6hz,6h),0.34(d,j＝2.9hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.5,148.2,139.8,138.5,136.5,134.7,133.7,128.9,128.1,127.9,127.6,121.7,121.4,116.5,46.1,35.8,34.6,32.7,28.3,22.8,22.6,21.4,-2.0,-2.0.hr-ms(ei)m/z calcd for c
26h34
n2osi
[m h

]419.2514,found 419.2518.
[0047]
3-{[dimethyl(phenyl)silyl]methyl}-6,6,6-trifluoro-n-(quinolin-8-yl)hexanamide(11)
[0048]1h-nmr(400mhz,cdcl3):δ＝9.70(s,1h),8.77(ddd,j＝21.7,5.6,1.9hz,2h),8.16(dd,j＝8.3,1.7hz,1h),7.59
–
7.52(m,3h),7.51
–
7.42(m,2h),7.33
–
7.31(m,3h),2.43(dd,j＝6.7,2.8hz,2h),2.30(p,j＝6.5hz,1h),2.07(qt,j＝10.8,8.2hz,2h),1.71
–
1.61(m,2h),1.04
–
0.85(m,2h),0.36(d,j＝1.7hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝170.4,148.3,139.0,138.5,136.5,134.5,133.6,129.2,128.1,127.6,126.0,121.8,121.7,116.6,45.2,31.4(q,3j
c-f
＝28.4hz),31.3,28.9,28.9,21.4,-2.1,-2.2.hr-ms(ei)m/z calcd for c
24h27
f3n2osi[m h

]445.1918,found 445.1917.
[0049]
6-cyano-3-{[dimethyl(phenyl)silyl]methyl}-n-(quinolin-8-yl)hexanamide(12)
[0050]1h-nmr(400mhz,cdcl3):δ＝9.71(s,1h),8.84
–
8.69(m,2h),8.16(dd,j＝8.2,1.7hz,1h),7.57
–
7.51(m,3h),7.51
–
7.42(m,2h),7.35
–
7.31(m,3h),7.51
–
7.42(m,2h),2.50
–
2.37(m,2h),2.28(hept,j＝6.5hz,1h),2.12(td,j＝7.2,1.6hz,2h),1.66
–
1.56(m,2h),1.53
–
1.41(m,2h),1.01
–
0.89(m,2h),0.36(d,j＝4.3hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝170.7,148.3,139.2,138.4,136.5,134.4,133.6,129.2,128.1,127.5,121.8,121.6,119.7,116.6,45.5,35.9,31.6,22.7,21.4,17.2,-2.1,-2.3.hr-ms(ei)m/z calcd for c
25h29
n3osi[m h

]416.2153,found 416.2153.
[0051]
ethyl7-{[dimethyl(phenyl)silyl]methyl}-9-oxo-9-(quinolin-8-ylamino)nonanoate(13)
[0052]1h-nmr(400mhz,cdcl3):δ＝9.71(s,1h),8.78(ddd,j＝9.0,5.8,1.7hz,2h),8.15(dd,j＝8.3,1.7hz,1h),7.55
–
7.50(m,3h),7.49
–
7.41(m,2h),7.29
–
7.27(m,3h),4.10(q,j＝7.1hz,2h),2.43(qd,j＝14.3,6.9hz,2h),2.23(dt,j＝15.3,7.1hz,3h),1.54(p,j＝7.8hz,2h),1.39
–
1.26(m,4h),1.23(t,j＝7.1hz,3h),1.21
–
1.12(m,2h),0.95(d,j＝6.8hz,2h),0.34(d,j＝2.4hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝173.9,171.3,148.2,136.4,134.7,133.7,128.9,128.1,127.9,127.6,121.7,121.4,116.5,60.2,46.0,36.6,34.4,32.3,29.4,26.2,25.1,21.3,14.4,-2.0,-2.0.hr-ms(ei)m/z calcd for c
29h38
n2o3si[m h

]491.2725,found 491.2724.
[0053]
3-{[dimethyl(phenyl)silyl]methyl}-5-(1,3-dioxan-2-yl)-n-(quinolin-8-yl)pentanamide(14)
[0054]1h-nmr(400mhz,cdcl3):δ＝9.70(s,1h),8.81
–
8.73(m,2h),8.15(dd,j＝8.3,1.7hz,1h),7.55
–
7.50(m,3h),7.49
–
7.41(m,2h),7.30
–
7.22(m,3h),4.36(t,j＝5.1hz,1h),4.07
–
3.98(m,2h),3.67(tq,j＝11.9,2.2hz,2h),2.49(dd,j＝14.3,6.8hz,1h),2.37(dd,j＝14.3,6.8hz,1h),2.27(p,j＝6.5hz,1h),2.02(dtt,j＝13.5,12.5,5.0hz,1h),1.66
–
1.58(m,2h),1.52
–
1.41(m,2h),1.28(dtt,j＝13.4,2.6,1.3hz,1h),0.95(dd,j＝6.7,3.5hz,2h),0.34(s,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.2,148.2,139.7,138.5,136.4,134.7,133.7,128.9,128.0,127.9,127.6,121.7,121.4,116.5,102.5,66.9,45.7,32.2,32.0,31.1,25.9,21.1,-2.0,-2.2.hr-ms(ei)m/z calcd for c
27h34
n2o3si[m h

]
463.2412,found 463.2412.
[0055]
7-chloro-3-{[dimethyl(phenyl)silyl]methyl}-n-(quinolin-8-yl)heptanamide(15)
[0056]1h-nmr(400mhz,cdcl3):δ＝9.72(s,1h),8.83
–
8.70(m,2h),8.16(dd,j＝8.2,1.7hz,1h),7.58
–
7.51(m,3h),7.51
–
7.42(m,2h),7.37
–
7.27(m,3h),3.42(t,j＝6.7hz,2h),2.52
–
2.35(m,2h),2.27(hept,j＝7.7,7.1hz,1h),1.63
–
1.53(m,2h),1.40(tdt,j＝11.5,8.6,5.6hz,4h),0.96(d,j＝6.8hz,2h),0.35(d,j＝4.3hz,5h).
13
c-nmr(100mhz,cdcl3):δ＝171.2,148.2,139.6,138.5,136.5,134.6,133.7,129.0,128.0(
×
2),127.6,121.7,121.5,116.5,45.9,45.1,35.9,32.7,32.2,23.8,21.3,-2.0,-2.1.hr-ms(ei)m/z calcd for c
25h31
cln2osi[m h

]439.1967,found 439.1964.
[0057]
6-[(tert-butyldimethylsilyl)oxy]-3-{[dimethyl(phenyl)silyl]methyl}-n-(quinolin-8-yl)hexa-namide(16)
[0058]1h-nmr(400mhz,cdcl3):δ＝9.71(s,1h),8.78(ddd,j＝9.0,5.8,1.7hz,2h),8.15(dd,j＝8.3,1.7hz,1h),7.55
–
7.50(m,3h),7.50
–
7.41(m,2h),7.39
–
7.26(m,3h),3.49(td,j＝6.5,1.4hz,2h),2.54
–
2.45(m,1h),2.40(dd,j＝14.3,6.7hz,1h),2.27(p,j＝6.6hz,1h),1.52(q,j＝7.0hz,2h),1.46
–
1.36(m,2h),1.02
–
0.91(m,2h),0.84(s,9h),0.34(s,6h),-0.01(d,j＝6.0hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.5,148.2,139.8,138.5,136.5,134.7,133.7,128.9,128.1,127.9,127.6,121.7,121.4,116.5,46.1,39.2,32.2,21.3,19.7,14.3,-1.9,-2.0.hr-ms(ei)m/z calcd for c
30h44
n2o2si2[m h

]521.3015,found 521.3014
[0059]
4-{[dimethyl(phenyl)silyl]methyl}-6-oxo-6-(quinolin-8-ylamino)hexylpivalate(17)
[0060]1h-nmr(400mhz,cdcl3):δ＝9.71(s,1h),8.82
–
8.70(m,2h),8.16(dd,j＝8.2,1.7hz,1h),7.55
–
7.52(m,3h),7.51
–
7.43(m,2h),7.32
–
7.29(m,3h),3.93(td,j＝6.5,2.9hz,2h),2.52
–
2.38(m,2h),2.29(hept,j＝7.6,7.0hz,1h),1.71
–
1.60(m,2h),1.44(dt,j＝9.1,6.5hz,2h),1.11(s,9h),0.40
–
0.30(m,6h).
13
c-nmr(100mhz,cdcl3):δ＝178.7,171.0,148.2,139.5,138.5,136.5,134.6,133.6,129.1,128.1,128.0,127.6,121.7,121.5,116.6,64.6,45.8,38.8,33.1,32.2,27.3,25.9,21.3,-2.0,-2.1.hr-ms(ei)m/z calcd for c
29h38
n2o3si[m h

]491.2725,found 491.2724.
[0061]
tert-butyl{3-{[dimethyl(phenyl)silyl]methyl}-5-(thiophen-2-yl)pentanoyl}(quinolin-8-yl)carbamate(18)
[0062]1h-nmr(400mhz,cdcl3):δ＝8.78(dd,j＝4.2,1.7hz,1h),8.12(dd,j＝8.3,1.7hz,1h),7.78(dd,j＝8.3,1.4hz,1h),7.57
–
7.48(m,3h),7.42(dd,j＝7.4,1.4hz,1h),7.36
–
7.29(m,4h),7.16(dd,j＝4.9,3.0hz,1h),3.23(dd,j＝16.6,6.4hz,1h),3.03(dd,j＝16.5,6.7hz,1h),2.60(dh,j＝14.4,7.4hz,2h),2.36(hept,j＝6.4hz,1h),1.69(dtd,j＝15.8,9.1,7.8,4.3hz,2h),1.20(s,9h),1.08
–
0.92(m,2h),0.30(d,j＝4.2hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝175.8,153.0,150.4,144.3,143.0,140.0,137.3,136.0,133.7,133.7,129.0,128.8,128.5,128.0,127.9,126.1,125.0,121.5,119.9,82.4,45.2,37.6,31.3,27.7,27.4,21.4,-1.9,-2.2.hr-ms(ei)m/z calcd for c
32h38
n2o3ssi[m h

]
459.1921,found 459.1920.
[0063]
3-{[dimethyl(phenyl)silyl]methyl}-5-phenyl-n-(quinolin-8-yl)pentanamide(19)
[0064]1h-nmr(400mhz,cdcl3):δ＝9.73(s,1h),8.84
–
8.71(m,2h),8.14(dd,j＝8.3,1.7hz,1h),7.56
–
7.50(m,3h),7.49
–
7.41(m,2h),7.34
–
7.25(m,3h),7.23
–
7.14(m,2h),7.14
–
7.08(m,1h),7.07
–
7.01(m,2h),2.64
–
2.50(m,3h),2.45(dd,j＝14.3,6.8hz,1h),2.32(hept,j＝6.5hz,1h),1.77
–
1.59(m,3h),1.02(d,j＝6.8hz,2h),0.33(d,j＝3.0hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.1,148.2,142.4,139.6,138.4,136.4,134.6,133.7,129.0,128.5,128.4,128.0,128.0,127.5,125.7,121.7,121.4,116.5,45.9,38.8,33.1,32.2,21.4,-2.0,-2.1.hr-ms(ei)m/z calcd for c
29h32
n2osi[m h

]453.2357,found 4532355.
[0065]
5-(4-chlorophenyl)-3-{[dimethyl(phenyl)silyl]methyl}-n-(quinolin-8-yl)pentanamide(20)
[0066]1h-nmr(400mhz,cdcl3):δ＝9.65(s,1h),8.79(dd,j＝4.2,1.7hz,1h),8.73(dd,j＝7.1,1.9hz,1h),8.16(dd,j＝8.2,1.7hz,1h),7.55
–
7.50(m,3h),7.49
–
7.43(m,2h),7.35
–
7.28(m,3h),7.17(d,j＝8.4hz,2h),7.02(d,j＝8.4hz,2h),2.48(dt,j＝13.3,6.7hz,1h),1.04
–
0.90(m,2h),0.33(d,j＝1.0hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.0,148.2,141.3,139.5,138.4,136.5,134.6,133.7,131.4,130.3,129.0,128.1,128.0,127.6,121.7,121.5,119.4,116.5,45.8,38.4,32.4,32.1,21.5,-1.9,-2.2.hr-ms(ei)m/z calcd for c
29h31
cln2osi[m h

]487.1967,found 487.1966.
[0067]
5-(4-bromophenyl)-3-{[dimethyl(phenyl)silyl]methyl}-n-(quinolin-8-yl)pentanamide(21)
[0068]1h-nmr(400mhz,cdcl3):δ＝9.71(s,1h),8.82
–
8.71(m,2h),8.16(dd,j＝8.3,1.7hz,1h),7.57
–
7.51(m,4h),7.51
–
7.43(m,2h),7.31(dt,j＝4.5,1.7hz,3h),7.29
–
7.25(m,2h),6.93
–
6.81(m,2h),2.64
–
2.41(m,4h),2.29(hept,j＝6.6hz,1h),1.71
–
1.57(m,2h),1.00(d,j＝6.8hz,2h),0.33(d,j＝3.4hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.0,148.2,141.3,139.5,138.4,136.5,134.6,133.7,131.4,130.3,129.0,128.1,128.0,127.6,121.7,121.5,119.4,116.5,45.8,38.4,32.4,32.1,21.5,-1.9,-2.2.hr-ms(ei)m/z calcd for c
29h31
brn2osi[m h

]531.1462,found 531.1465.
[0069]
6-(4-chloro-3-methylphenoxy)-3-{[dimethyl(phenyl)silyl]methyl}-n-(quinolin-8-yl)hexanamide(22)
[0070]1h-nmr(400mhz,cdcl3):δ＝9.73(s,1h),8.89
–
8.67(m,2h),8.14(dd,j＝8.3,1.7hz,1h),7.58
–
7.50(m,3h),7.52
–
7.39(m,2h),7.31
–
7.28(m,3h),7.13(d,j＝8.7hz,1h),6.65(d,j＝2.9hz,1h),6.55(dd,j＝8.7,3.0hz,1h),3.75(td,j＝6.5,1.5hz,2h),2.53
–
2.40(m,2h),2.38
–
2.30(m,1h),2.28(s,3h),1.76(tdd,j＝11.1,6.5,2.9hz,2h),1.52(dt,j＝9.0,5.9hz,2h),0.99(d,j＝6.8hz,2h),0.36(d,j＝1.7hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.1,157.6,148.2,139.5,138.4,136.9,136.5,134.6,133.7,129.6,129.0,128.1,127.9,127.5,125.6,121.7,121.5,117.1,116.5,113.1,68.1,45.9,33.0,32.1,26.2,21.4,20.4,-2.0,-2.0.hr-ms(ei)m/z calcd for c
31h35
cln2o2si[m h

]
531.2230,found 531.2234.
[0071]
6-(4-chlorophenoxy)-3-{[dimethyl(phenyl)silyl]methyl}-n-(quinolin-8-yl)hexanamide(23)
[0072]1h-nmr(400mhz,cdcl3):δ＝9.72(s,1h),8.81
–
8.70(m,2h),8.15(dd,j＝8.3,1.7hz,1h),7.53(ddd,j＝7.2,5.2,3.0hz,3h),7.51
–
7.41(m,2h),7.34
–
7.26(m,3h),7.18
–
7.12(m,2h),6.74
–
6.65(m,2h),3.76(td,j＝6.5,1.0hz,2h),2.53
–
2.40(m,2h),2.32(p,j＝6.5hz,1h),1.76(ddt,j＝11.1,8.6,4.6hz,2h),1.56
–
1.47(m,2h),0.99(d,j＝6.8hz,2h),0.35(d,j＝1.9hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.1,157.7,148.2,139.5,138.5,136.5,134.6,133.7,129.3,129.0,128.1,128.0,127.6,125.4,121.7,121.6,116.6,115.8,68.3,45.9,32.9,32.1,26.2,21.4,-2.0,-2.1.hr-ms(ei)m/z calcd for c
30h33
cln2o2si[m h

]517.2073,found 517.2075.
[0073]
benzyl4-(2-{[dimethyl(phenyl)silyl]methyl}-4-oxo-4-(quinolin-8-ylamino)butyl)piperidine-1-carboxylate(24)
[0074]1h-nmr(400mhz,cdcl3):δ＝9.71(s,1h),8.81
–
8.72(m,2h),8.16(dd,j＝8.3,1.7hz,1h),7.56
–
7.51(m,3h),7.51
–
7.42(m,2h),7.38
–
7.30(m,5h),7.31
–
7.29(m,3h),5.11(d,j＝11.2hz,2h),4.05(s,2h),2.65(s,2h),2.49
–
2.37(m,2h),2.31(p,j＝6.6hz,1h),1.46
–
1.42(m,1h),1.38
–
1.16(m,4h),1.00
–
0.88(m,4h),0.34(d,j＝3.3hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.0,155.3,148.2,139.5,138.4,137.1,136.5,134.5,133.7,129.1,128.6,128.1,128.0,128.0,127.9,127.6,121.7,121.5,116.5,67.0,46.2,44.3,44.2,36.2,33.6,33.4,32.2,29.1,22.0,-1.9,-2.0.hr-ms(ei)m/z calcd for c
35h41
n3o3si[m h

]580.2990,found 580.2991.
[0075]
3-{[dimethyl(phenyl)silyl]methyl}-n-(quinolin-8-yl)oct-7-enamide(25)
[0076]1h-nmr(400mhz,cdcl3):δ＝9.71(s,1h),8.82
–
8.73(m,2h),8.15(dd,j＝8.2,1.7hz,1h),7.53
–
7.52(m,3h),7.50
–
7.41(m,2h),7.31
–
7.27(m,3h),5.72(ddt,j＝16.9,10.2,6.7hz,1h),4.97
–
4.82(m,2h),2.48(dd,j＝14.3,7.1hz,1h),2.39(dd,j＝14.4,6.6hz,1h),2.26(dt,j＝12.5,6.0hz,1h),1.95
–
1.90(m,2h),1.38(q,j＝3.9,2.6hz,4h),0.96(d,j＝6.8hz,2h),0.34(d,j＝2.6hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.4,148.2,139.7,139.0,138.5,136.5,134.7,133.7,128.9,128.1,127.9,127.6,121.7,121.4,116.5,114.5,46.0,36.3,34.0,32.3,25.9,21.4,-2.0,-2.0.hr-ms(ei)m/z calcd for c
26h32
n2osi[m h

]417.2357,found 417.2355.
[0077]
3-{[dimethyl(phenyl)silyl]methyl}-n-(quinolin-8-yl)non-8-enamide(26)
[0078]1h-nmr(400mhz,cdcl3):δ＝9.72(s,1h),8.82
–
8.72(m,2h),8.15(dd,j＝8.3,1.7hz,1h),7.56
–
7.50(m,3h),7.49
–
7.41(m,2h),7.33
–
7.26(m,3h),5.74(ddt,j＝16.9,10.1,6.7hz,1h),4.97
–
4.83(m,2h),2.48(dd,j＝14.3,7.1hz,1h),2.39(dd,j＝14.3,6.7hz,1h),2.26(p,j＝6.3hz,1h),2.08
–
1.88(m,2h),1.45
–
1.17(m,6h),0.96(d,j＝6.8hz,2h),0.34(d,j＝3.0hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.4,148.2,139.8,139.1,138.4,136.5,134.7,133.7,128.9,128.1,127.9,127.6,121.7,121.4,116.5,114.3,46.0,36.6,33.8,32.4,29.1,26.0,21.4,-2.0,-2.0.hr-ms(ei)m/z calcd for c
27h34
n2osi[m h

]431.2514,found 431.2514.
[0079]
3-{[dimethyl(phenyl)silyl]methyl}-n-(quinolin-8-yl)butanamide(27)
[0080]1h-nmr(400mhz,cdcl3):δ＝9.76(d,j＝26.2hz,1h),8.99
–
8.64(m,2h),8.16(dd,j＝8.3,1.6hz,1h),7.58
–
7.50(m,3h),7.50
–
7.41(m,2h),7.40
–
7.28(m,2h),2.62
–
2.30(m,3h),1.12
–
1.03(m,1h),0.91
–
0.78(m,1h),0.34(d,j＝1.2hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.3,148.2,139.8,138.5,136.5,134.7,133.7,128.9,128.1,127.9,127.6,121.7,121.4,116.5,49.4,27.8,24.2,15,-1.8,-2.0.hr-ms(ei)m/z calcd for c
22h23
d3n2osi[m h

]366.2076,found 366.2077.
[0081]
n-(quinolin-8-yl)-3-[(trimethylsilyl)methyl]butanamide(28)
[0082]1h-nmr(400mhz,cdcl3):δ＝9.81(s,1h),8.87
–
8.78(m,2h),8.18(dd,j＝8.3,1.7hz,1h),7.60
–
7.45(m,3h),2.59
–
2.41(m,2h),2.44
–
2.34(m,1h),0.84(dd,j＝14.6,4.5hz,1h),0.60(dd,j＝14.6,9.4hz,1h),0.07(s,9h).
13
c-nmr(100mhz,cdcl3):δ＝171.5,148.2,138.5,136.5,134.7,128.1,127.6,121.7,121.5,116.5,49.6,27.9,25.2,-0.5.hr-ms(ei)m/z calcd for c
17h21
d3n2osi[m h

]304.1919,found 304.1920.
[0083]
6-phenyl-n-(quinolin-8-yl)-3-((trimethylsilyl)methyl)hexanamide(29)
[0084]1h-nmr(400mhz,cdcl3):δ＝δ9.91(s,1h),8.93
–
8.89(m,2h),8.28(dd,j＝8.3,1.7hz,1h),7.69
–
7.61(m,2h),7.57(dd,j＝8.3,4.2hz,1h),7.38
–
7.32(m,2h),7.31
–
7.18(m,3h),2.76
–
2.69(m,2h),2.69
–
2.54(m,2h),2.40(p,j＝6.6hz,1h),1.66
–
1.54(m,2h),0.82(d,j＝6.9hz,2h),0.15(s,9h).
13
c-nmr(100mhz,cdcl3):δ＝171.5,148.2,142.7,138.5,136.5,134.7,128.5,128.4,128.1,127.6,125.8,121.7,121.5,116.5,77.4,46.2,36.5,36.3,32.4,28.7,22.2,-0.5.hr-ms(ei)m/z calcd for c
25h32
n2osi[m h

]405.2357,found 405.2355.
[0085]
tert-butyl[3-methyl-4-(methyldiphenylsilyl)butanoyl](quinolin-8-yl)carbamate(30)
[0086]1h-nmr(400mhz,cdcl3):δ＝8.8(dd,j＝4.2,1.7hz,1h),8.1(dd,j＝8.3,1.7hz,1h),7.8(dd,j＝8.2,1.4hz,1h),7.6
–
7.5(m,5h),7.4(dd,j＝7.3,1.4hz,1h),7.4
–
7.3(m,7h),3.2
–
3.0(m,2h),2.5
–
2.4(m,1h),1.5(dd,j＝14.8,4.2hz,1h),1.2(s,9h),1.1(dd,j＝14.8,9.9hz,1h),1.0(d,j＝6.7hz,3h),0.6(s,3h).
13
c-nmr(100mhz,cdcl3):δ＝175.7,153.0,150.5,144.3,138.2,137.8,137.3,136.0,134.7,134.6,129.1,129.1,128.0,127.9,127.9,126.2,121.5,82.5,76.9,48.7,27.8,27.2,23.2,22.5,-3.4.hr-ms(ei)m/z calcd for c
32h36
n2o3si[m h

]525.2568,found 525.2566.
[0087]
3-{[dimethyl(phenyl)silyl]methyl}-2,6-dimethyl-n-(quinolin-8-yl)heptanamide(31)
[0088]1h-nmr(400mhz,cdcl3):δ＝9.94
–
9.67(m,1h),8.85
–
8.64(m,2h),8.15(dd,j＝8.3,1.7hz,1h),7.56
–
7.49(m,3h),7.49
–
7.38(m,2h),7.36
–
7.26(m,3h),2.73
–
2.64(m,0.21h),2.64
–
2.56(m,0.79h),2.07
–
1.89(m,1h),1.41
–
1.25(m,4h),1.25
–
1.15(m,4h),1.10
–
0.97(m,2h),0.96
–
0.80(m,2h),0.77(d,j＝6.6hz,4h),0.36
–
0.25(m,6h).
13
c-nmr(100mhz,cdcl3):δ＝174.8,174.4,148.2,148.1,139.8,138.6,136.4,134.8,134.2,134.1,133.7,133.6,129.0,128.9,128.8,128.1,127.9,127.9,127.8,127.8,127.7,127.7,127.6,121.7,121.3,116.5,77.4,46.9,45.7,38.3,38.2,36.3,35.4,30.6,29.8,
28.5,28.3,23.0,22.7,22.5,18.5,14.3,-2.1,-2.2,-2.4,-2.6.hr-ms(ei)m/z calcd for c
27h36
n2osi[m h

]433.2670,found 4332671.
[0089]
4-{[dimethyl(phenyl)silyl]methyl}-7-methyl-n-(quinolin-8-yl)octanamide(32)
[0090]1h-nmr(400mhz,cdcl3):δ＝9.75(s,1h),8.85
–
8.71(m,2h),8.17(dd,j＝8.3,1.7hz,1h),7.58
–
7.51(m,3h),7.50
–
7.42(m,1h),7.34
–
7.27(m,3h),2.47(ddd,j＝9.0,6.7,2.1hz,2h),1.78(dtdd,j＝27.2,13.3,9.3,6.5hz,2h),1.62(q,j＝6.3hz,1h),1.40(tq,j＝13.2,6.6hz,1h),1.28(ddt,j＝11.8,6.4,3.1hz,3h),1.20
–
1.05(m,2h),0.87
–
0.79(m,8h),0.32(s,6h).
13
c-nmr(100mhz,cdcl3):δ＝172.2,148.2,140.0,138.5,136.5,134.7,133.7,128.9,128.1,127.9,127.6,121.7,121.4,116.5,35.7,35.6,34.2,34.0,32.3,28.5,22.8,22.7,21.2,-1.9,-2.0.hr-ms(ei)m/z calcd for c
27h36
n2osi[m h

]433.2670,found 433.2669.
[0091]
5-[dimethyl(phenyl)silyl]-4-methyl-n-(quinolin-8-yl)pentanamide(33)
[0092]1h-nmr(400mhz,cdcl3):δ＝9.77(s,1h),8.85
–
8.72(m,2h),8.16(dd,j＝8.3,1.7hz,1h),7.60
–
7.50(m,3h),7.50
–
7.41(m,2h),7.31
–
7.41(m,2h),2.59
–
2.44(m,2h),1.89
–
1.65(m,3h),1.28
–
1.26(m,2h),0.95(d,j＝5.9hz,2h),0.31(d,j＝1.8hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝172.1,148.2,140.0,138.4,136.6,134.7,133.6,128.9,128.1,127.9,127.6,121.7,121.4,116.6,36.3,36.1,29.5,24.1,22.8,-1.8,-1.9.hr-ms(ei)m/z calcd for c
23h28
n2osi[m h

]377.2044,found 377.2042.
[0093]
4-{[dimethyl(phenyl)silyl]methyl}-n-(quinolin-8-yl)heptanamide(34)
[0094]1h-nmr(400mhz,cdcl3):δ＝9.74(s,1h),8.87
–
8.68(m,2h),8.16(dd,j＝8.3,1.7hz,1h),7.59
–
7.50(m,3h),7.50
–
7.42(m,2h),7.34
–
7.28(m,3h),2.55
–
2.38(m,2h),1.87
–
1.70(m,2h),1.30
–
1.24(m,5h),0.89
–
0.77(m,5h),0.32(s,6h).
13
c-nmr(100mhz,cdcl3):δ＝172.2,148.2,140.0,138.5,136.5,134.7,133.6,128.9,128.1,127.9,127.6,121.7,121.4,116.6,38.6,35.5,33.7,32.3,21.1,19.6,14.4,-1.9,-1.9.hr-ms(ei)m/z calcd for c
25h32
n2osi[m h

]405.2357,found 405.2355.
[0095]
4-[dimethyl(phenyl)silyl]-3-(4-methylbenzyl)-n-(quinolin-8-yl)butanamide(35)
[0096]1h-nmr(400mhz,cdcl3):δ＝9.63(s,1h),8.82
–
8.72(m,2h),8.14(dd,j＝8.3,1.7hz,1h),7.56
–
7.49(m,3h),7.48
–
7.42(m,2h),7.34
–
7.27(m,4h),7.04
–
7.02(d,j＝8.3hz,2h),6.99(d,j＝8.3hz,2h),2.74
–
2.62(m,1h),2.60
–
2.47(m,2h),2.46
–
2.30(m,2h),2.26(s,3h),1.00(qd,j＝14.9,6.3hz,2h),0.34(s,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.2,148.1,140.4,139.5,138.4,137.9,136.4,134.6,133.7,130.2,129.0,128.2,128.0,127.9,127.5,126.8,126.5,121.7,121.4,116.5,45.1,43.3,34.2,21.5,21.1,-1.9.hr-ms(ei)m/z calcd for c
29h32
n2osi[m h

]453.2357,found 453.2359.
[0097]
3-[4-(tert-butyl)benzyl]-4-[dimethyl(phenyl)silyl]-n-(quinolin-8-yl)butanamide(36)
[0098]1h-nmr(400mhz,cdcl3):δ＝9.64(s,1h),8.82
–
8.70(m,2h),8.13(dd,j＝8.2,1.7hz,1h),7.55
–
7.46(m,4h),7.45
–
7.41(m,1h),7.32
–
7.27(m,3h),7.25
–
7.21(m,2h),
7.08
–
7.00(m,2h),2.76
–
2.66(m,1h),2.58
–
2.48(m,2h),2.48
–
2.30(m,2h),1.25(s,9h),1.10
–
0.94(m,2h),0.35(d,j＝3.3hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.2,148.8,148.1,139.5,138.4,137.3,136.5,134.7,133.7,129.1,129.0,128.0,127.9,127.6,125.2,121.6,121.4,116.5,45.2,42.9,34.4,34.2,31.5,21.3,-1.9,-2.0.hr-ms(ei)m/z calcd for c
32h38
n2osi[m h

]495.2827,found 495.2825.
[0099]
4-[(1,1'-biphenyl)-4-yl]-3-{[dimethyl(phenyl)silyl]methyl}-n-(quinolin-8-yl)butanamide(37)
[0100]1h-nmr(400mhz,cdcl3):δ＝9.66(s,1h),8.83
–
8.68(m,2h),8.13(dt,j＝8.3,2.1hz,1h),7.59
–
7.51(m,3h),7.51
–
7.48(m,2h),7.48
–
7.41(m,4h),7.41
–
7.34(m,2h),7.33
–
7.27(m,4h),7.18(d,j＝8.2hz,2h),2.77
–
2.62(m,2h),2.61
–
2.53(m,1h),2.43(qd,j＝14.6,6.3hz,2h),1.10
–
0.98(m,2h),0.36(d,j＝2.0hz,5h).
13
c-nmr(100mhz,cdcl3):δ＝171.1,148.1,141.2,139.6,139.4,139.0,138.4,136.4,134.6,134.1,133.7,129.9,129.0,128.8,128.1,128.0,127.5,127.1,127.1,121.7,121.4,116.5,45.1,43.1,34.3,21.2,-1.9,-2.0.hr-ms(ei)m/z calcd for c
34h34
n2osi[m h

]515.2514,found 515.2514.
[0101]
4-[dimethyl(phenyl)silyl]-3-(naphthalen-2-ylmethyl)-n-(quinolin-8-yl)butanamide(38)
[0102]1h-nmr(400mhz,cdcl3):δ＝9.52(s,1h),8.66
–
8.55(m,2h),7.98(dd,j＝8.3,1.7hz,1h),7.64
–
7.53(m,3h),7.42
–
7.37(m,3h),7.37
–
7.30(m,2h),7.30
–
7.23(m,3h),7.18
–
7.09(m,4h),2.76
–
2.61(m,2h),2.53(p,j＝6.8hz,1h),2.36
–
2.23(m,2h),0.98
–
0.85(m,2h),0.22(d,j＝0.8hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.0,148.1,139.4,138.4,138.1,136.4,134.6,133.7,133.6,132.2,129.0,128.0,127.8,127.6,127.6,127.5,125.9,125.3,121.6,121.4,116.5,45.0,43.6,34.2,21.1,-1.9,-2.0.hr-ms(ei)m/z calcd for c
32h32
n2osi[m h

]489.2357,found 489.2355.
[0103]
4-[dimethyl(phenyl)silyl]-n-(quinolin-8-yl)-3-[4-(trifluoromethyl)benzyl]butanamide(39)
[0104]1h-nmr(400mhz,cdcl3):δ＝9.65(s,1h),8.79(dd,j＝4.2,1.7hz,1h),8.72(dd,j＝7.0,2.0hz,1h),8.15(dd,j＝8.3,1.7hz,1h),7.55
–
7.46(m,4h),7.48
–
7.41(m,3h),7.31(dt,j＝4.6,1.8hz,3h),7.19(d,j＝8.0hz,2h),2.77
–
2.63(m,2h),2.54(p,j＝6.7hz,1h),2.47
–
2.31(m,2h),0.98(qd,j＝14.9,6.7hz,2h),0.34(d,j＝2.5hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝170.7,148.2,144.7,139.1,138.4,136.5,134.5,133.7,129.7,129.1,128.4(q,j＝32hz),128.1,128.0,127.5,125.2(q,j＝4hz),124.5(q,j＝272hz),121.7,121.6,116.5,44.8,43.2,34.1,21.1,-2.0,-2.1.
19
f-nmr(376mhz,cdcl3):δ＝-62.3.hr-ms(ei)m/z calcd for c
29h29
f3n2osi[m h

]507.2074,found 507.2071.
[0105]
4-[dimethyl(phenyl)silyl]-n-(quinolin-8-yl)-3-(4-(trifluoromethoxy)benzyl)butanamide(40)
[0106]1h-nmr(400mhz,cdcl3):δ＝9.66(s,1h),8.82
–
8.67(m,2h),8.15(dd,j＝8.3,1.7hz,1h),7.55
–
7.50(m,3h),7.50
–
7.43(m,3h),7.31(ddt,j＝5.5,3.7,2.1hz,3h),7.10(d,j＝8.7hz,2h),7.05(d,j＝7.9hz,2h),2.64(d,j＝7.0hz,2h),2.57
–
2.43(m,1h),2.39(d,j＝6.5hz,2h),0.98(qd,j＝14.9,6.6hz,2h),0.34(d,j＝1.8hz,6h).
13
c-nmr(100mhz,
cdcl3):δ＝170.8,148.2,139.3,139.2,138.4,136.5,134.5,133.7,130.7,129.1,128.1,128.0,127.5,121.7,121.5,120.9,119.3,116.6,44.8,42.7,34.3,21.0,-2.0,-2.1.
19
f-nmr(376mhz,cdcl3):δ＝-57.9.hr-ms(ei)m/z calcd for c
29h29
f3n2o2si[m h

]523.2024,found 523.2025.
[0107]
4-[dimethyl(phenyl)silyl]-3-(4-fluorobenzyl)-n-(quinolin-8-yl)butanamide(41)
[0108]1h-nmr(400mhz,cdcl3):δ＝9.65(s,1h),8.79(dd,j＝4.2,1.7hz,1h),8.74(dd,j＝7.2,1.8hz,1h),8.15(dd,j＝8.3,1.7hz,1h),7.56
–
7.49(m,3h),7.49
–
7.43(m,2h),7.34
–
7.28(m,3h),7.08
–
7.01(m,2h),6.94
–
6.86(m,2h),2.61(d,j＝6.9hz,2h),2.48(dt,j＝13.3,6.7hz,1h),2.41
–
2.31(m,2h),1.04
–
0.91(m,2h),0.33(s,6h).
13
c-nmr(100mhz,cdcl3):δ＝170.9,161.4(d,1j
c-f
＝246hz),148.1,139.3,138.4,136.5,136.1(d,4j
c-f
＝3hz),134.5,133.7,130.8(d,3j
c-f
＝8hz),129.0,128.0,128.0,127.5,121.7,121.5,116.5,115.1(d,2j
c-f
＝21hz),44.8,42.5,34.4,20.9,-2.0,-2.0.
19
f-nmr(376mhz,cdcl3):δ＝-117.5.hr-ms(ei)m/z calcd for c
28h29
fn2osi[m h

]457.2106,found 457.2105.
[0109]
4-[dimethyl(phenyl)silyl]-3-(3-methylbenzyl)-n-(quinolin-8-yl)butanamide(42)
[0110]1h-nmr(400mhz,cdcl3):δ＝9.65(s,1h),8.82
–
8.70(m,2h),8.13(dd,j＝8.3,1.7hz,1h),7.55
–
7.49(m,3h),7.48
–
7.41(m,2h),7.31
–
7.26(m,3h),7.11(t,j＝7.5hz,1h),6.97
–
6.87(m,3h),2.71
–
2.61(m,1h),2.59
–
2.49(m,2h),2.47
–
2.31(m,2h),2.26(s,3h),1.09
–
0.93(m,2h),0.34(d,j＝1.2hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.2,148.1,140.4,139.5,138.4,137.9,136.4,134.6,133.7,130.2,129.0,128.2,128.0,127.9,127.5,126.8,126.5,121.7,121.4,116.5,45.1,43.3,34.2,21.5,21.1,-1.9.hr-ms(ei)m/z calcd for c
29h32
n2osi[m h

]453.2357,found 453.2356.
[0111]
3-(4-chlorobenzyl)-4-[dimethyl(phenyl)silyl]-n-(quinolin-8-yl)butanamide(43)
[0112]1h-nmr(400mhz,cdcl3):δ＝9.65(s,1h),8.79(dd,j＝4.2,1.7hz,1h),8.73(dd,j＝7.1,1.9hz,1h),8.16(dd,j＝8.2,1.7hz,1h),7.55
–
7.50(m,3h),7.49
–
7.43(m,2h),7.35
–
7.28(m,3h),7.22
–
7.11(m,2h),7.06
–
6.97(m,2h),2.61(d,j＝6.9hz,2h),2.48(p,j＝6.7hz,1h),2.40
–
2.35(m,2h),1.04
–
0.90(m,2h),0.33(d,j＝1.0hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝170.8,148.2,142.6,139.2,138.4,136.5,134.5,134.1,133.7,129.6,129.5,129.1,128.0,128.0,127.7,127.5,126.3,121.7,121.5,116.5,44.8,43.0,34.2,21.0,-2.0,-2.0.hr-ms(ei)m/z calcd for c
28h29
cln2osi[m h

]473.1811,found 473.1815.
[0113]
3-(4-bromobenzyl)-4-[dimethyl(phenyl)silyl]-n-(quinolin-8-yl)butanamide(44)
[0114]1h-nmr(400mhz,cdcl3):δ＝9.64(s,1h),8.79(dd,j＝4.2,1.7hz,1h),8.73(dt,j＝7.2,1.5hz,1h),8.14(dd,j＝8.3,1.7hz,1h),7.55
–
7.49(m,3h),7.49
–
7.41(m,2h),7.34
–
7.28(m,5h),7.00
–
6.92(m,2h),2.66
–
2.55(m,2h),2.38
–
2.36(m,2h),1.03
–
0.89(m,2h),0.33(t,j＝1.1hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝170.8,148.2,139.5,139.2,
138.4,136.5,134.5,133.7,131.4,131.2,129.1,128.1,128.0,127.5,121.7,121.5,119.9,116.5,44.8,42.8,34.2,21.0,-2.0,-2.0.hr-ms(ei)m/z calcd for c
28h29
brn2osi[m h

]517.1306,found 517.1308.
[0115]
3-(4-cyanobenzyl)-4-[dimethyl(phenyl)silyl]-n-(quinolin-8-yl)butanamide(45)
[0116]1h-nmr(400mhz,cdcl3):δ＝9.64(s,1h),8.79(dd,j＝4.2,1.7hz,1h),8.71(dd,j＝6.6,2.4hz,1h),8.16(dd,j＝8.3,1.7hz,1h),7.61
–
7.50(m,3h),7.50
–
7.42(m,5h),7.32(d,j＝3.4hz,2h),7.17(d,j＝8.2hz,2h),2.78
–
2.62(m,2h),2.52(p,j＝6.7hz,1h),2.47
–
2.31(m,2h),1.05
–
0.88(m,2h),0.34(d,j＝1.8hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝170.5,148.2,146.3,138.9,138.4,136.6,134.4,133.7,132.1,130.2,129.2,128.1,127.5,121.8,121.7,119.2,116.5,109.9,44.7,43.5,34.1,21.2,-2.1,-2.1.hr-ms(ei)m/z calcd for c
29h29
n3osi[m h

]464.2153,found 464.2155.
[0117]
methyl4-(2-{[dimethyl(phenyl)silyl]methyl}-4-oxo-4-(quinolin-8-ylamino)butyl)benzoate(46)
[0118]1h-nmr(400mhz,cdcl3):δ＝9.64(s,1h),8.79(dd,j＝4.2,1.7hz,1h),8.73(dd,j＝7.1,1.9hz,1h),8.15(dd,j＝8.3,1.7hz,1h),7.92
–
7.84(m,2h),7.55
–
7.49(m,3h),7.49
–
7.43(m,2h),7.30(dp,j＝5.5,2.0hz,3h),7.20
–
7.14(m,2h),3.88(s,3h),2.76
–
2.64(m,2h),2.54(dq,j＝13.6,6.7hz,1h),2.44
–
2.31(m,2h),0.98(qd,j＝14.9,6.7hz,2h).
13
c-nmr(100mhz,cdcl3):δ＝170.8,167.2,148.2,146.2,139.2,138.4,136.5,134.5,133.7,129.7,129.5,129.1,128.1,128.1,128.0,127.5,121.7,121.5,116.6,52.1,44.9,43.5,34.2,21.1,-2.0,-2.0.hr-ms(ei)m/z calcd for c
30h32
n2o3si[m h

]497.2255,found 497.2253.
[0119]
3-(4-benzoylbenzyl)-4-(dimethyl(phenyl)silyl)-n-(quinolin-8-yl)butanamide(47)
[0120]1h-nmr(400mhz,cdcl3):δ＝9.67(s,1h),8.79(dd,j＝4.2,1.7hz,1h),8.74(dd,j＝7.2,1.9hz,1h),8.15(dd,j＝8.3,1.7hz,1h),7.77
–
7.71(m,2h),7.71
–
7.64(m,2h),7.59
–
7.52(m,3h),7.52
–
7.48(m,2h),7.47
–
7.43(m,3h),7.31(dd,j＝4.7,2.0hz,3h),7.24
–
7.17(m,2h),2.74(d,j＝7.0hz,2h),2.59(p,j＝6.8hz,1h),2.42(d,j＝6.5hz,2h),1.02(qd,j＝14.9,6.7hz,2h),0.36(s,6h).
13
c-nmr(100mhz,cdcl3):δ＝196.6,170.8,148.2,145.8,139.2,138.4,138.0,136.5,135.5,134.5,133.7,132.3,130.4,130.1,129.4,129.1,128.3,128.0,127.5,121.7,121.6,116.5,44.9,43.5,34.2,21.2,-2.0.hr-ms(ei)m/z calcd for c
35h34
n2o2si[m h

]543.2463,found 543.2469.
[0121]
4-(dimethyl(phenyl)silyl)-3-(4-(pyrrolidin-1-ylsulfonyl)benzyl)-n-(quinolin-8-yl)butanamide(48)
[0122]1h-nmr(400mhz,cdcl3):δ＝9.68(s,1h),8.81(dd,j＝4.2,1.7hz,1h),8.73(dd,j＝6.8,2.3hz,1h),8.17(dd,j＝8.3,1.8hz,1h),7.68(d,j＝7.9hz,2h),7.55
–
7.45(m,5h),7.37
–
7.27(m,3h),7.24(d,j＝8.0hz,2h),3.21(q,j＝6.1,4.9hz,4h),2.76(dd,j＝13.4,7.4hz,1h),2.67(dd,j＝13.4,6.4hz,1h),2.53(p,j＝6.7hz,1h),2.46
–
2.32(m,2h),1.77
–
1.63(m,4h),1.04
–
0.89(m,2h),0.33(s,6h).
13
c-nmr(100mhz,cdcl3):δ＝170.6,148.3,
146.0,139.0,138.4,136.6,134.6,134.4,133.7,130.0,129.2,128.1,127.7,127.5,121.8,121.7,116.6,48.0,44.8,43.2,34.1,27.2,25.3,21.0,-2.1,-2.1.hr-ms(ei)m/z calcd for c
32h37
n3o3ssi[m h

]572.2398,found 572.2399.
[0123]
3-(3-chlorobenzyl)-4-[dimethyl(phenyl)silyl]-n-(quinolin-8-yl)butanamide(49)
[0124]1h-nmr(400mhz,cdcl3):δ＝9.66(s,1h),8.80(dd,j＝4.2,1.7hz,1h),8.74(dd,j＝7.2,1.7hz,1h),8.14(dd,j＝8.3,1.7hz,1h),7.55
–
7.49(m,3h),7.49
–
7.41(m,2h),7.33
–
7.29(m,3h),7.17
–
7.06(m,3h),6.98(dt,j＝6.9,1.8hz,1h),2.61(d,j＝7.0hz,2h),2.50(p,j＝6.7hz,1h),2.38(d,j＝6.4hz,2h),1.05
–
0.90(m,2h),0.34(d,j＝1.6hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝170.8,148.2,142.6,139.2,138.4,136.5,134.5,134.1,133.7,129.6,129.5,129.1,128.0,128.0,127.7,127.5,126.3,121.7,121.5,116.5,44.8,43.0,34.2,21.0,-2.0,-2.0.hr-ms(ei)m/z calcd for c
28h29
cln2osi[m h

]473.1811,found 473.1815.
[0125]
3-(3-bromobenzyl)-4-[dimethyl(phenyl)silyl]-n-(quinolin-8-yl)butanamide(50)
[0126]1h-nmr(400mhz,cdcl3):δ＝9.67(s,1h),8.80(dd,j＝4.2,1.7hz,1h),8.74(dd,j＝7.2,1.8hz,1h),8.14(dd,j＝8.2,1.7hz,1h),7.55
–
7.49(m,3h),7.49
–
7.42(m,2h),7.34
–
7.28(m,3h),7.28
–
7.21(m,2h),7.11
–
6.99(m,2h),2.60(d,j＝7.0hz,2h),2.49(p,j＝6.7hz,1h),2.42
–
2.34(m,2h),1.06
–
0.88(m,2h),0.34(d,j＝1.6hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝170.8,148.2,143.0,139.2,138.4,136.5,134.5,133.7,132.4,129.9,129.3,129.1,128.1,128.0,127.5,122.5,121.7,121.5,116.5,77.3,77.0,76.7,44.8,43.0,34.2,21.0,-2.0,-2.0.hr-ms(ei)m/z calcd for c
28h29
cln2osi[m h

]517.1306,found 517.1305.
[0127]
4-[dimethyl(phenyl)silyl]-3-(4-nitrobenzyl)-n-(quinolin-8-yl)butanamide(51)
[0128]1h-nmr(400mhz,cdcl3):δ＝9.66(s,1h),8.80(dd,j＝4.3,1.7hz,1h),8.70(dd,j＝6.2,2.8hz,1h),8.16(dd,j＝8.3,1.7hz,1h),8.06
–
7.79(m,1h),7.51(dd,j＝6.1,2.4hz,4h),7.49
–
7.40(m,2h),7.37
–
7.32(m,3h),2.78(dd,j＝13.6,7.6hz,1h),2.71(dd,j＝13.6,6.4hz,1h),2.55(p,j＝6.7hz,1h),2.45(dd,j＝14.7,5.7hz,1h),2.36(dd,j＝14.8,7.3hz,1h),1.02(dd,j＝14.9,7.0hz,1h),0.93(dd,j＝14.9,6.4hz,1h),0.35(d,j＝2.9hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝170.5,148.3,142.6,138.9,138.4,136.5,135.7,134.4,133.7,129.3,129.2,128.1,127.5,124.2,121.8,121.7,121.3,116.5,44.8,43.1,34.2,21.2,-2.0,-2.1.hr-ms(ei)m/z calcd for c
28h29
n3o3si[m h

]484.2051,found 484.2054.
[0129]
3-(3,4-dichlorobenzyl)-4-[dimethyl(phenyl)silyl]-n-(quinolin-8-yl)butanamide(52)
[0130]1h-nmr(400mhz,cdcl3):δ＝9.65(s,1h),8.80(dd,j＝4.3,1.7hz,1h),8.72(dd,j＝7.0,2.0hz,1h),8.16(dt,j＝8.3,2.1hz,1h),7.58
–
7.50(m,3h),7.50
–
7.42(m,1h),7.32(dp,j＝4.7,1.6hz,3h),7.26
–
7.22(m,1h),7.15(d,j＝2.1hz,1h),2.65
–
2.54(m,2h),
2.50
–
2.43(m,1h),2.42
–
2.29(m,2h),0.99(dd,j＝14.9,6.7hz,1h),0.92(dd,j＝14.9,6.2hz,1h),0.34(d,j＝2.5hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝
13
c-nmr(100mhz,cdcl3):δ＝170.6,148.2,140.9,139.0,138.4,136.5,134.4,133.7,132.2,131.3,130.2,129.2,128.9,128.1,127.5,121.7,121.6,116.6,44.8,42.5,34.1,21.0,-2.0,-2.1.hr-ms(ei)m/z calcd for c
28h28cl2
n2osi[m h

]507.1421,found 507.1422.
[0131]
3-(4-bromo-2-fluorobenzyl)-4-[dimethyl(phenyl)silyl]-n-(quinolin-8-yl)butanamide(53)
[0132]1h-nmr(400mhz,cdcl3):δ＝9.65(s,1h),8.79(dd,j＝4.3,1.7hz,1h),8.71(dd,j＝7.2,1.9hz,1h),8.15(dd,j＝8.3,1.7hz,1h),7.54
–
7.49(m,3h),7.49
–
7.41(m,2h),7.30(dq,j＝4.8,2.5hz,3h),7.10(d,j＝8.3hz,2h),6.97(t,j＝7.9hz,1h),2.72
–
2.64(m,1h),2.64
–
2.57(m,1h),2.57
–
2.47(m,1h),2.44
–
2.32(m,2h),1.04(dd,j＝14.9,6.2hz,1h),0.93(dd,j＝14.9,6.7hz,1h),0.35(d,j＝7.6hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝170.7,161.2(d,1j
c-f
＝249hz),148.2,139.2,138.4,136.5,134.5,133.7,132.8,132.8,129.1,128.0,128.0,127.5,127.3(d,4j
c-f
＝4hz),121.7,121.5,119.9(d,3j
c-f
＝10hz),118.9(d,2j
c-f
＝26hz),116.5,44.9,36.0,33.2,21.3,-2.1,-2.2.
19
f-nmr(376mhz,cdcl3):δ＝-114.3.hr-ms(ei)m/z calcd for c
28h28
brfn2osi[m h

]535.1212,found 535.1216.
[0133]
3-benzyl-4-[dimethyl(phenyl)silyl]-2-methyl-n-(quinolin-8-yl)butanamide(54)
[0134]1h-nmr(400mhz,cdcl3):δ＝9.83(s,1h),8.86
–
8.69(m,2h),8.17(dd,j＝8.3,1.7hz,1h),7.58
–
7.51(m,3h),7.50
–
7.43(m,2h),7.38
–
7.27(m,3h),7.26
–
7.21(m,2h),7.19
–
7.12(m,3h),2.72(dd,j＝13.9,8.2hz,1h),2.65
–
2.49(m,2h),2.31
–
2.17(m,1h),1.28
–
1.21(m,1h),1.19(d,j＝7.0hz,3h),0.88(dd,j＝15.2,8.1hz,1h),0.33(d,j＝11.7hz,5.17h),0.27(d,j＝7.6hz,0.78h).
13
c-nmr(100mhz,cdcl3):δ＝173.9,148.1,141.0,139.3,138.7,136.5,134.7,133.8,129.5,129.1,128.5,128.0,127.6,126.0,121.7,121.4,116.6,77.4,76.9,44.7,40.9,40.5,40.4,17.1,14.2,-2.1,-2.2.hr-ms(ei)m/z calcd for c
29h32
n2osi[m h

]453.2357,found 453.2358.
[0135]
3-(4-chlorobenzyl)-4-[dimethyl(phenyl)silyl]-2-methyl-n-(quinolin-8-yl)butanamide(55)
[0136]
1h-nmr(400mhz,cdcl3):δ＝9.80(s,1h),8.82(dd,j＝4.2,1.7hz,1h),8.77(dd,j＝7.2,1.9hz,1h),8.18(dd,j＝8.3,1.7hz,1h),7.58
–
7.51(m,3h),7.53
–
7.44(m,2h),7.35
–
7.31(m,3h),7.16(d,j＝8.4hz,2h),7.04(d,j＝8.4hz,2h),2.70(dd,j＝13.9,7.9hz,1h),2.56(td,j＝7.0,3.2hz,1h),2.50(dd,j＝13.8,6.8hz,1h),2.23(q,j＝8.7,7.2hz,1h),1.20(d,j＝7.0hz,2.49h),1.13(d,j＝5.9hz,0.58h),0.97
–
0.73(m,2h),0.33(d,j＝6.2hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝173.7,148.2,139.4,139.1,138.6,136.5,134.6,133.7,131.8,130.8,129.1,128.5,128.0,127.6,121.8,121.5,116.6,44.7,40.8,39.6,17.2,13.7,-2.1,-2.2.hr-ms(ei)m/z calcd for c
29h31
cln2osi[m h

]487.1967,found 487.1966.
[0137]
3-methyl-n-(quinolin-8-yl)-4-(m-tolyl)butanamide(56)
[0138]1h-nmr(400mhz,cdcl3):δ＝9.78(s,1h),8.86
–
8.72(m,2h),8.15(dd,j＝8.3,
1.7hz,1h),7.54
–
7.47(m,2h),7.45(dd,j＝8.3,4.3hz,1h),7.20
–
7.13(m,1h),7.05
–
6.98(m,3h),2.80
–
2.68(m,1h),2.58
–
2.51(m,3h),2.31(s,3h),1.05(d,j＝6.2hz,3h).
13
c-nmr(100mhz,cdcl3):δ＝171.3,148.2,140.4,137.9,136.5,134.6,130.2,128.3,128.1,127.6,126.9,126.5,125.5,121.7,121.5,116.6,77.4,45.2,43.2,32.8,21.5,19.8.hr-ms(ei)m/z calcd for c
21h22
n2o[m h

]319.1805,found 319.1802.
[0139]
3-benzyl-n-(quinolin-8-yl)-4-(trimethylsilyl)butanamide(57)
[0140]1h-nmr(400mhz,cdcl3):δ＝9.83(s,1h),8.92
–
8.80(m,2h),8.22(dd,j＝8.3,1.7hz,1h),7.64
–
7.54(m,2h),7.52(dd,j＝8.2,4.2hz,1h),7.39
–
7.29(m,4h),7.29
–
7.21(m,1h),2.87(dd,j＝13.4,5.9hz,1h),2.75(dd,j＝13.4,7.7hz,1h),2.69
–
2.61(m,1h),2.61
–
2.46(m,2h),0.95
–
0.73(m,2h),0.15(s,9h).
13
c-nmr(100mhz,cdcl3):δ＝171.2,148.2,140.6,138.5,136.5,134.6,129.5,128.4,128.1,127.6,126.1,121.7,121.4,116.5,45.2,43.5,34.3,22.1,-0.5.hr-ms(ei)m/z calcd for c
23h28
n2osi[m h

]377.2044,found 377.2046.
[0141]
3-(4-methylbenzyl)-n-(quinolin-8-yl)-4-(trimethylsilyl)butanamide(58)
[0142]1h-nmr(400mhz,cdcl3):δ＝9.75(s,1h),8.83(dd,j＝4.2,1.7hz,1h),8.79(dd,j＝7.4,1.7hz,1h),8.18(dd,j＝8.3,1.7hz,1h),7.58
–
7.49(m,2h),7.47(dd,j＝8.3,4.2hz,1h),7.15(d,j＝8.0hz,2h),7.09(d,j＝7.8hz,2h),2.79(dd,j＝13.1,5.2hz,1h),2.63(dd,j＝13.1,7.8hz,1h),2.59
–
2.48(m,2h),2.47
–
2.38(m,1h),2.30(s,3h),0.78(qd,j＝14.8,6.3hz,2h),0.10(s,9h).
13
c-nmr(100mhz,cdcl3):δ＝171.3,148.2,138.5,137.4,136.5,135.6,134.7,129.4,129.1,128.1,127.6,121.7,121.4,116.5,45.3,43.1,34.3,22.2,21.1,-0.4.hr-ms(ei)m/z calcd for c
24h30
n2osi[m h

]391.2201,found 391.2205.
[0143]
3-benzyl-4-(methyldiphenylsilyl)-1-(pyrrolidin-1-yl)butan-1-one(59)
[0144]1h-nmr(400mhz,cdcl3):δ＝7.51
–
7.44(m,4h),7.34
–
7.29(m,6h),7.25
–
7.19(m,2h),7.18
–
7.10(m,1h),7.07
–
6.99(m,2h),3.42
–
3.27(m,2h),2.99
–
2.86(m,2h),2.59(d,j＝7.0hz,2h),2.46(p,j＝6.7hz,1h),2.09(dd,j＝15.5,6.2hz,1h),2.00(dd,j＝15.5,6.7hz,1h),1.77
–
1.69(m,5h),1.34(dd,j＝15.0,6.6hz,1h),1.22(dd,j＝15.0,6.6hz,1h),0.61(s,3h).
13
c-nmr(100mhz,cdcl3):δ＝170.7,140.9,137.7,137.6,134.7,134.6,129.5,129.2,128.2,127.9,126.0,46.3,45.5,43.8,41.3,33.3,26.1,24.4,19.3,-3.4.hr-ms(ei)m/z calcd for c
28h33
nosi[m h

]428.2405,found 428.2406.
[0145]
(6r)-3-{[dimethyl(phenyl)silyl]methyl}-6,10-dimethyl-n-(quinolin-8-yl)undec-9-enamide(60)
[0146]1h-nmr(400mhz,cdcl3):δ＝9.71(s,1h),8.83
–
8.72(m,2h),8.15(dd,j＝8.3,1.7hz,1h),7.57
–
7.50(m,3h),7.49
–
7.40(m,2h),7.29(dt,j＝4.0,1.9hz,3h),5.08
–
4.97(m,1h),2.56
–
2.44(m,1h),2.44
–
2.32(m,1h),2.23(p,j＝6.4hz,1h),1.97
–
1.86(m,2h),1.65(s,3h),1.55(s,3h),1.40
–
1.19(m,5h),1.15
–
1.00(m,2h),0.99
–
0.90(m,2h),0.77(d,j＝6.1hz,3h),0.34(dd,j＝3.2,1.0hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.5,148.2,139.8,138.5,136.4,134.7,133.7,128.9,128.1,127.9,127.6,121.7,121.4,116.5,46.1,46.0,37.3,37.0,34.2,33.8,32.8,32.7,25.8,25.7,25.6,21.5,21.4,19.7,19.6,17.8,-2.0,-2.0.hr-ms(ei)m/z calcd for c
31h42
n2osi[m h

]487.3140,found 487.3142.
[0147]
(3ar,5r,6s,6ar)-5-[(s)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl4-{[dimethyl(phenyl)silyl]methyl}-6-oxo-6-(quinolin-8-ylamino)hexanoate(61)
[0148]1h-nmr(400mhz,cdcl3):δ＝9.70(s,1h),8.78(s,0h),8.76(dd,j＝7.2,1.8hz,1h),8.16(dd,j＝8.3,1.7hz,1h),7.53(ddd,j＝7.4,5.0,3.0hz,3h),7.51
–
7.41(m,2h),7.30(dd,j＝4.9,1.9hz,3h),5.80(dd,j＝3.6,2.4hz,1h),4.86
–
4.77(m,2h),4.28(ddd,j＝7.0,5.8,4.1hz,1h),4.13(dd,j＝8.2,4.1hz,1h),4.03(dd,j＝8.5,6.9hz,1h),3.87(ddd,j＝8.6,5.8,1.1hz,1h),2.53
–
2.39(m,2h),2.26(tdd,j＝12.9,9.5,6.3hz,3h),1.70
–
1.63(m,2h),1.44
–
1.26(m,12h),0.97(d,j＝6.7hz,2h),0.35(s,6h).
13
c-nmr(100mhz,cdcl3):δ＝172.7,171.1,148.2,139.5,136.5,134.6,133.6,129.0,128.1,128.0,127.6,121.7,121.5,116.6,113.2,110.1,104.2,77.8,75.1,72.5,65.6,45.6,36.3,34.1,32.1,32.1,26.8,26.4,25.1,21.9,21.2,-2.0,-2.1.hr-ms(ei)m/z calcd for c
36h46
n2o8si[m na

]685.2916,found 685.2918.
[0149]
3-{[dimethyl(phenyl)silyl]methyl}-6-{[(8r,9s,13s,14s)-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydrospiro[cyclopenta[a]phenanthrene-17,2'-[1,3]dioxolan]-3-yl]oxy}-n-(quinolin-8-yl)hexanamide(62)
[0150]1h-nmr(400mhz,cdcl3):δ＝9.72(s,1h),8.82
–
8.65(m,2h),8.15(dd,j＝8.3,1.7hz,1h),7.57
–
7.50(m,3h),7.50
–
7.41(m,2h),7.29(dd,j＝5.0,1.7hz,3h),7.14(d,j＝8.6hz,1h),6.61(dd,j＝8.6,2.7hz,1h),6.53(d,j＝2.6hz,1h),3.99
–
3.85(m,4h),3.78(t,j＝6.6hz,2h),2.79(t,j＝8.1hz,2h),2.47(qd,j＝14.3,6.8hz,2h),2.35
–
2.27(m,2h),2.06
–
1.98(m,1h),1.90
–
1.81(m,2h),1.54
–
1.49(m,2h),1.41
–
1.31(m,3h),0.99(d,j＝6.7hz,2h),0.87(s,3h),0.35(s,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.2,157.0,148.2,139.6,138.5,138.0,136.5,134.6,133.7,132.6,129.0,128.1,128.0,127.6,126.3,121.7,121.5,119.6,116.5,114.6,112.1,68.0,65.4,64.7,49.5,46.3,45.9,43.8,39.2,34.4,33.1,32.2,30.9,29.9,27.1,26.5,26.3,22.5,21.3,14.5,-2.0,-2.0.hr-ms(ei)m/z calcd for c
44h54
n2o4si[m na

]725.3746,found 725.3750.
[0151]
(7r)-7-{[3r,5r,8r,9s,10s,13r,14s]-3-[(tert-butyldimethylsilyl)oxy]-10,13-dimethylhexadecahydro-1h-cyclopenta[a]phenanthren-17-yl}-3-{[dimethyl(phenyl)silyl]methyl}-n-(quinolin-8-yl)octanamide(63)
[0152]1h-nmr(400mhz,cdcl3):δ＝9.73(s,1h),8.84
–
8.73(m,2h),8.17(ddd,j＝8.3,4.3,1.7hz,1h),7.53(ddd,j＝6.7,4.4,2.4hz,3h),7.51
–
7.43(m,2h),7.33
–
7.27(m,3h),3.58(dq,j＝10.6,5.4,4.7hz,1h),2.53
–
2.35(m,2h),2.32
–
2.20(m,1h),1.93
–
1.66(m,5h),1.39
–
0.91(m,28h),0.89(s,9h),0.87
–
0.79(m,5h),0.56(d,j＝6.9hz,3h),0.34(d,j＝2.8hz,6h),0.06(s,6h).
13
c-nmr(100mhz,cdcl3):δ＝171.5,148.2,139.8,138.5,136.5,134.7,133.7,128.9,128.1,127.9,127.6,121.7,121.4,116.5,73.0,56.5,56.4,56.2,56.1,46.2,42.8,42.4,40.3,40.3,40.2,37.4,37.1,36.1,36.0,35.8,35.7,34.7,32.6,32.5,31.2,28.4,27.5,27.1,26.5,26.1,24.3,23.5,22.8,21.5,20.9,18.8,18.5,12.1,-1.9,-2.0,-4.4.hr-ms(ei)m/z calcd for c
51h78
n2o2si2[m h

]807.5675,found 807.5677.
[0153]
6-[(tert-butoxycarbonyl)(quinolin-8-yl)amino]-4-{[dimethyl(phenyl)
silyl]methyl}-6-oxohexyl2-(1-(4-chlorobenzoyl)-6-methoxy-2-methyl-1h-indol-3-yl)acetate(64)
[0154]1h-nmr(400mhz,cdcl3):δ＝8.81(dd,j＝4.1,1.6hz,1h),8.14(dd,j＝8.3,1.7hz,1h),7.79(dd,j＝8.2,1.4hz,1h),7.68
–
7.60(m,2h),7.51(dd,j＝6.3,2.2hz,3h),7.47
–
7.35(m,4h),7.31(q,j＝2.9hz,3h),6.95(d,j＝2.6hz,1h),6.92
–
6.83(m,1h),6.66(dd,j＝9.0,2.7hz,1h),3.97(t,j＝6.7hz,2h),3.81(s,3h),3.61(s,2h),3.12(dd,j＝16.7,6.6hz,1h),2.98(dd,j＝16.7,6.4hz,1h),2.34(d,j＝7.7hz,3h),2.27(q,j＝6.5hz,1h),1.60(ddd,j＝16.4,8.0,4.2hz,4h),1.19(s,8h),0.90
–
0.84(m,2h).
13
c-nmr(100mhz,cdcl3):δ＝13c nmr(101mhz,chloroform-d)δ175.7,171.0,168.4,156.2,153.0,150.4,144.3,139.9,139.3,137.2,136.0,134.5,134.3,134.1,133.7,131.3,130.9,130.8,129.2,129.0,128.9,128.1,127.9,126.2,121.6,115.1,112.9,111.8,101.4,82.5,65.5,55.8,45.1,33.0,31.1,30.4,27.8,25.8,21.4,13.5,-1.9,-2.0.hr-ms(ei)m/z calcd for c
48h52
cln3o7si[m h

]846.3336,found 846.3335.
[0155]
6-[(tert-butoxycarbonyl)(quinolin-8-yl)amino]-4-{[dimethyl(phenyl)silyl]methyl}-6-oxohexyl 4-(n,n-dipropylsulfamoyl)benzoate(65)
[0156]1h-nmr(400mhz,cdcl3):δ＝8.80(dd,j＝4.2,1.7hz,1h),8.14(dd,j＝8.3,1.7hz,1h),8.11
–
8.03(m,2h),7.84
–
7.76(m,3h),7.56
–
7.50(m,3h),7.43(dd,j＝7.3,1.4hz,1h),7.38
–
7.30(m,4h),4.21(td,j＝6.5,2.6hz,2h),3.18(dd,j＝16.6,6.8hz,1h),3.13
–
3.04(m,5h),2.36(p,j＝6.1hz,1h),1.76(p,j＝7.2hz,2h),1.53(dd,j＝10.1,4.9hz,6h),1.19(s,9h),1.05(dd,j＝14.9,6.1hz,1h),0.96(d,j＝7.5hz,1h),0.87(t,j＝7.4hz,7h),0.33(d,j＝2.7hz,6h).
13
c-nmr(100mhz,cdcl3):δ＝175.7,165.4,153.0,150.4,144.2,144.1,139.8,137.2,136.1,133.9,133.7,130.3,129.0,128.9,128.1,127.9,127.0,126.1,121.6,82.5,66.0,50.0,45.1,33.0,31.1,27.7,25.8,22.0,21.4,11.3,-1.9,-2.1.hr-ms(ei)m/z calcd for c
42h55
n3o7ssi[m h

]774.3603,found 774.3605.
[0157]
本发明进一步研究了本发明新型固体硅锌试剂在烯烃双官能团化反应中的底物适用性和官能团兼容性等方面的考察。该反应体系表现出广泛的底物适用性和优秀的官能团兼容性，并且可以顺利的进行反应放大至克级规模，反应效率保持不变。该反应也可在敞口空气下进行，再次说明该类硅锌试剂对空气的良好稳定性。此外，该反应可以进一步应用于具有药理学活性的天然产物以及药物分子的结构修饰，从而也进一步说明了该类锌试剂，以及该合成方法学在药物化学领域具有潜在的应用价值。具体反应果如图4所示。
[0158]
显然，上述实施例仅仅是为清楚地说明所作的举例，并非对实施方式的限定。对于所属领域的普通技术人员来说，在上述说明的基础上还可以做出其它不同形式变化或变动。这里无需也无法对所有的实施方式予以穷举。而由此所引申出的显而易见的变化或变动仍处于本发明创造的保护范围之中。