环丙烷因具有很强的环张力被广泛用于各类开环反应研究[1-14]. 在环丙烷上同时引入一系列吸电子基团和给电子基团后, 其环的活性也会随之发生变化, 这一类环丙烷被称为供受体(D-A)环丙烷[15]. 由于受到供电子基团和吸电子基团对相邻两个碳原子的极化作用, D-A环丙烷在酸催化下可以选择性地断裂C—C键生成1,3-偶极子, 进而发生开环、环加成及重排等反应. 亲核试剂对D-A环丙烷选择性开环反应是D-A环丙烷常见的反应之一. 该开环反应通常在路易斯酸催化下进行, 通过路易斯酸金属中心与D-A环丙烷中的两个吸电子基配位进行活化, 然后亲核试剂以类SN2的方式进攻D-A环丙烷的C(2)位置, 发生开环反应, 生成单官能化或双官能化的链状化合物. 胺类化合物作为常见且易得的氮源, 被作为氮亲核试剂应用于D-A环丙烷的开环反应[16-17].
以仲胺为例, 2012年, 唐勇课题组[18]报道了2-取代环丙烷-1,1-二羧酸酯与多取代仲胺的对映选择性开环反应, 该反应采用Ni(Ⅱ)络合物作为催化剂, 在温和条件下, 以高达99%的产率和98%对映选择性得到了目标产物, 且具有良好的底物适用性. 2018年, Banerjee课题组[19]报道了N-苄基苯胺在对甲苯磺酰胺(PTSA)催化下对D-A环丙烷的选择性开环反应. 2021年, 翟宏斌和赵华[20]等报道了以Sc(OTf)3为催化剂, 咔唑为氮亲核试剂对D-A环丙烷的开环反应. Kim课题组[21]将仲胺换为叔胺后, 由于氮上没有氢, 三元环开环后进攻氨基对位, 发生了芳环上的亲电取代反应(Scheme 1).
1 结果与讨论
在此基础上, 以无取代的全芳基β-氨基酮1a和D-A环丙烷2a为模型反应, 进行条件优化. Yb(OTf)3作催化剂, 将溶剂HFIP换为乙腈, 常温下反应0.5 h, 以64%的产率得到了目标产物3a(表1, Entry 1). 延长反应时间, 产率有所下降(表1, Entries 2, 3); 缩短到0.25 h, 产率为51%(表1, Entry 4). 考察其他溶剂对反应的影响, 使用超干乙腈和二氯甲烷产率都有所下降(表1, Entries 5, 6), 使用四氢呋喃和乙醇均不反应(表1, Entries 7, 8). 通过薄层色谱(TLC)发现, 1a与2a的物质的量之比为1∶1时1a未完全反应, 故加大2a的用量, 对反应物投料比进行了筛选, 当1a与2a的物质的量之比为1∶2.5时, 产率达到了87%(表1, Entry 11). 最后对催化剂的用量进行优化, 结果表明, 随着催化剂用量的增大, 产率也有所提升(表1, Entries 13~15), 但当催化剂的用量增加到100 mol%时, 产率却降低到78%(表1, Entry 16). 因此, 最优的反应条件为: 以乙腈作溶剂, 50 mol% Yb(OTf)3为催化剂, n(1a)∶n(2a)=1∶2.5, 在常温下反应0.5 h.
表1 反应条件的优化Table 1 Optimization of the reaction conditions  |
| Entry | Catalyst (Dosage/mol%) | Solvent | n(1a)∶n(2a) | Time/h | Yield of 3a/% |
|---|---|---|---|---|---|
| 1 | Yb(OTf)3 (20) | CH3CN | 1∶1 | 0.5 | 64 |
| 2 | Yb(OTf)3 (20) | CH3CN | 1∶1 | 1 | 49 |
| 3 | Yb(OTf)3 (20) | CH3CN | 1∶1 | 5 | 46 |
| 4 | Yb(OTf)3 (20) | CH3CN | 1∶1 | 0.25 | 51 |
| 5 | Yb(OTf)3 (20) | Dry CH3CN | 1∶1 | 0.5 | 48 |
| 6 | Yb(OTf)3 (20) | DCM | 1∶1 | 0.5 | 29 |
| 7 | Yb(OTf)3 (20) | THF | 1∶1 | 0.5 | NR |
| 8 | Yb(OTf)3 (20) | CH3CH2OH | 1∶1 | 0.5 | NR |
| 9 | Yb(OTf)3 (20) | CH3CN | 1∶1.5 | 0.5 | 64 |
| 10 | Yb(OTf)3 (20) | CH3CN | 1∶2 | 0.5 | 81 |
| 11 | Yb(OTf)3 (20) | CH3CN | 1∶2.5 | 0.5 | 87 |
| 12 | Yb(OTf)3 (20) | CH3CN | 1∶3 | 0.5 | 84 |
| 13 | Yb(OTf)3 (30) | CH3CN | 1∶2.5 | 0.5 | 82 |
| 14 | Yb(OTf)3 (40) | CH3CN | 1∶2.5 | 0.5 | 85 |
| 15 | Yb(OTf)3 (50) | CH3CN | 1∶2.5 | 0.5 | 94 |
| 16 | Yb(OTf)3 (100) | CH3CN | 1∶2.5 | 0.5 | 78 |
在最优条件下进行底物拓展研究, 一系列具有不同取代基的β-氨基酮均可与D-A环丙烷发生反应, 均以较高的产率得到目标化合物(表2). 当酮的苯基上有吸电子基团和给电子基团时, 都能以良好的产率得到目标化合物(3b~3h), 且带吸电子基的底物的产率高于带给电子基的底物. 苄胺的苯基上有吸电子基团或给电子基团时, 以中等至良好的产率得到目标化合物(3i~3n, 63%~94%). 苯胺的间位为吸电子基溴(3o)和给电子基甲基(3p)时, 均以86%的产率得到目标化合物; 但当苯胺的对位有取代基时, 环丙烷开环在苯胺的邻位进行亲电取代反应. 接下来考察D-A环丙烷苯基上甲氧基的位置对反应的影响. 当甲氧基位于邻位(3s)时, 产率降到了37%, 位于间位未得到目标化合物; 而间位和对位都有甲氧基取代(3t)时, 相比对位取代产率有所下降; 邻、间、对位都有甲氧基取代(3u)时, 产率达到了72%. 当酮上的取代基为噻吩基和甲基时, 分别以80%和98%的产率得到目标化合物3v和3w.
表2 底物拓展Table 2 Evaluation of substrate scope  |
 |
为了探索这种反应的实用性, 进行了3a的克级规模合成实验. 如Eq. 1所示, 以β-氨基酮1a (3.0 mmol)和D-A环丙烷2a (7.0 mmol)为反应底物, 在最优条件下得到1.6172 g产物3a(产率95%).
为了探究碳基对反应的影响, 使用0.2 mol N-苄基苯胺4a和0.5 mol D-A环丙烷2a在最优条件下, 即50 mol% Yb(OTf)3、乙腈作溶剂, 常温下反应30 min, 以54%的产率得到在N-苄基苯胺的N上进行SN2取代反应的产物5a (Eq. 2). 而对于N-苄基苯胺和D-A环丙烷的反应, Tharmalingam课题组[23]在2019年就报道了D-A环丙烷在铜源的催化下在仲胺上进行了SN2取代反应. 实验结果更进一步表明碳基对反应存在影响. 单晶数据表明了碳基与氮氢之间存在分子间氢键, 从而导致开环反应发生在苯胺对位.
2 结论
D-A环丙烷在Lewis酸Yb(OTf)3的催化下, 开环形成1,3偶极子, 进攻β-氨基酮中氨基对位, 发生了芳环的亲电取代反应. 该反应以乙腈作溶剂, 室温下反应0.5 h, 产率最高可达94%. 反应条件温和、快速, 该反应与常见的在仲胺上进行的亲核取代反应生成叔胺不同, 为芳香仲胺和D-A环丙烷的选择性反应提供了新的合成思路.
3 实验部分
3.1 仪器与试剂
核磁共振1H NMR、13C NMR使用 Bruker Avance III 400 HD型核磁共振仪(CDCl3为溶剂, TMS为内标)测定; 高分辨质谱在配备有来自Thermo Scientific的APCI源的Q Exactive质谱仪和LTQ Orbitrap XL质谱仪上获得; X射线衍射在Bruker D8 Venture photon II衍射仪上测定, 使用APEX III程序获得. 柱色谱使用的硅胶(200~300 目)购买于烟台新诺新材料技术有限公司, 石油醚和乙酸乙酯购买于上海泰坦科技股份有限公司(General-reagent), 其他试剂购买于上海泰坦科技股份有限公司(Adamas-beta). 所有试剂均为分析纯, 反应中所需无水溶剂直接购买使用.
3.2 实验方法
3.2.1 原料的合成
3.2.2 化合物3的合成
称取三氟甲磺酸镱(0.05 mmol, 31.0 mg)、全芳基β-氨基酮1a (0.1 mmol, 30.1 mg)和D-A环丙烷2a (0.25 mmol, 66.0 mg), 并将其依次加入反应管中, 再加入2 mL乙腈, 常温下反应0.5 h, 薄层色谱(TLC)检测反应结束后, 通过硅胶柱层析(石油醚/乙酸乙酯, V∶V=5∶1)分离得到无色油状的目标化合物3a. 以相同的方法合成了化合物3b~3w.
2-(2-(4-甲氧基苯基)-2-(4-((3-氧代-1,3-二苯基丙基)氨基)基)乙基)丙二酸二甲酯(3a): 无色油状物, 产率94%. 1H NMR (400 MHz, CDCl3) δ: 7.88 (d, J=7.2 Hz, 2H), 7.54 (t, J=7.2 Hz, 1H), 7.44~7.40 (m, 4H), 7.30 (t, J=7.6 Hz, 2H), 7.22 (t, J=7.6 Hz, 1H), 7.07 (d, J=8.8 Hz, 2H), 6.91 (d, J=8.8 Hz, 2H), 6.77 (d, J=8.8 Hz, 2H), 6.47 (d, J=8.8 Hz, 2H), 4.97~4.90 (m, 1H), 4.48 (s, 1H), 3.73 (s, 3H), 3.69 (d, J=7.6 Hz, 1H), 3.66 (d, J=2.0 Hz, 3H), 3.64 (s, 3H), 3.46 (dd, J=16.0, 5.2 Hz, 1H), 3.37 (dd, J=16.0, 8.0 Hz, 1H), 3.24 (t, J=7.6 Hz, 1H), 2.52 (t, J=7.6 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 198.2, 169.9, 158.0, 145.6, 143.1, 136.6, 136.2, 136.2, 133.4, 132.8, 128.8, 128.7, 128.4, 128.2, 127.3, 126.3, 113.9, 113.8, 55.2, 54.9, 52.5, 50.1, 47.0, 46.4, 34.9, 34.8; HRMS (ESI) calcd for C35H35NO6Br (M＋H)＋ 566.2537, found 566.2557.
2-(2-(4-((3-(4-氯苯基)-3-氧代-1-苯丙基)氨基)苯基)-2-(4-甲氧基苯基)乙基)丙二酸二甲酯(3b): 无色油状物, 产率92%. 1H NMR (400 MHz, CDCl3) δ: 7.80 (d, J=8.8 Hz, 2H), 7.39 (dd, J=8.0, 3.6 Hz, 4H), 7.30 (t, J=7.6 Hz, 2H), 7.22 (t, J=7.2 Hz, 1H), 7.07 (d, J=8.8 Hz, 2H), 6.91 (d, J=8.4 Hz, 2H), 6.77 (d, J=8.6 Hz, 2H), 6.47 (d, J=8.4 Hz, 2H), 4.96~4.90 (m, 1H), 4.44 (s, 1H), 3.74 (s, 3H), 3.70 (d, J=8.4 Hz, 1H), 3.66 (s, 3H), 3.64 (s, 3H), 3.45~3.32 (m, 2H), 3.24 (t, J=6.4 Hz, 1H), 2.52 (t, J=8.8 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 197.0, 169.9, 169.9, 158.0, 145.4, 142.9, 139.9, 136.2, 135.0, 133.0, 129.6, 129.0, 128.9, 128.7, 128.5, 127.5, 126.4, 114.0, 113.9, 55.2, 54.9, 52.5, 50.1, 47.0, 46.3, 34.9, 34.9; HRMS (ESI) calcd for C35H35NO6Cl (M＋H)＋ 600.2147, found 600.2145.
2-(2-(4-((3-(4-溴苯基)-3-氧代-1-苯丙基)氨基)苯基)-2-(4-甲氧基苯基)乙基)丙二酸二甲酯(3c): 无色油状物, 产率93%. 1H NMR (400 MHz, CDCl3) δ: 7.89 (d, J=7.2 Hz, 2H), 7.56 (d, J=11.6 Hz, 2H), 7.44 (t, J=7.6 Hz, 2H), 7.36 (d, J=7.6 Hz, 2H), 7.18 (t, J=7.6 Hz, 1H), 7.08 (d, J=8.8 Hz, 2H), 6.92 (d, J=8.4 Hz, 2H), 6.78 (d, J=8.8 Hz, 2H), 6.45 (d, J=8.4 Hz, 2H), 4.93~4.84 (m, 1H), 4.47 (s, 1H), 3.75 (s, 3H), 3.71 (d, J=8.0 Hz, 1H), 3.67 (d, J=2.0 Hz, 3H), 3.65 (s, 3H), 3.44 (dd, J=16.4, 5.2 Hz, 1H), 3.36 (dd, J=16.4, 7.6 Hz, 1H), 3.25 (t, J=7.2 Hz, 1H), 2.52 (t, J=7.2 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 197.7, 169.9, 169.9, 158.0, 145.8, 145.2, 136.5, 136.1, 133.6, 133.2, 130.6, 130.5, 129.4, 128.8, 128.5, 128.2, 125.1, 123.0, 113.9, 55.2, 54.6, 52.5, 50.1, 47.0, 46.2, 34.87; HRMS (ESI) calcd for C35H35NO6Br (M＋H)＋ 644.1642, found 644.1643.
2-(2-(4-((3-(4-碘苯基)-3-氧代-1-苯丙基)氨基)苯基)-2-(4-甲氧基苯基)乙基)丙二酸二甲酯(3d): 无色油状物, 产率89%. 1H NMR (400 MHz, CDCl3) δ: 7.79 (s, 2H), 7.56 (d, J=8.4 Hz, 2H), 7.39 (d, J=7.2 Hz, 2H), 7.30 (t, J=7.6 Hz, 2H), 7.22 (t, J=7.2 Hz, 1H), 7.07 (d, J=8.4 Hz, 2H), 6.91 (d, J=8.4 Hz, 2H), 6.76 (s, 2H), 6.45 (s, 2H), 4.95~4.89 (m, 1H), 4.42 (s, 1H), 3.74 (s, 3H), 3.70 (dd, J=5.2, 2.0 Hz, 1H), 3.66 (d, J=2.0 Hz, 3H), 3.65 (d, J=1.2 Hz, 3H), 3.42~3.30 (m, 2H), 3.24 (td, J=7.2, 2.0 Hz, 1H), 2.52 (t, J=7.6 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 197.6, 169.8, 169.9, 158.0, 145.4, 142.9, 138.0, 136.2, 135.9, 133.0, 129.6, 128.9, 128.7, 128.5, 127.5, 126.4, 114.0, 113.9, 101.5, 55.2, 54.9, 52.5, 50.1, 47.0, 46.2, 34.9, 34.9; HRMS (ESI) calcd for C35H35NO6I (M＋H)＋ 692.1504, found 692.1506.
2-(2-(4-甲氧基苯基)-2-(4-((3-氧代-1-苯基-3-(4-(三氟甲基)苯基)丙基)氨基)苯基)乙基)丙二酸二甲酯(3e): 无色油状物, 产率92%. 1H NMR (400 MHz, CDCl3) δ: 7.96 (d, J=8.4 Hz, 2H), 7.68 (d, J=8.4 Hz, 2H), 7.40 (d, J=7.2 Hz, 2H), 7.31 (t, J=7.6 Hz, 2H), 7.25~7.22 (m, 1H), 7.08 (d, J=8.8 Hz, 2H), 6.93 (d, J=8.4 Hz, 2H), 6.78 (d, J=8.8 Hz, 2H), 6.48 (d, J=8.4 Hz, 2H), 4.96 (t, J=6.4 Hz, 1H), 4.39 (s, 1H), 3.74 (s, 3H), 3.71 (d, J=8.8 Hz, 1H), 3.67 (d, J=2.0 Hz, 3H), 3.65 (s, 3H), 3.50~3.39 (m, 2H), 3.25 (td, J=7.2, 1.6 Hz, 1H), 2.52 (t, J=7.6 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 197.4, 169.8, 169.9, 158.1, 145.3, 142.7, 139.3, 136.1, 134.6 (d, J=32.3 Hz), 133.1, 128.9, 128.7, 128.6, 128.5, 128.5, 127.6, 126.4, 125.8 (q, J=3.0 Hz), 124.8, 122.2, 114.0, 113.9, 55.2, 54.7, 52.5, 50.2, 47.4, 46.5, 34.9, 34.9; HRMS (ESI) calcd for C36H35F3NO6 (M＋H)＋ 634.2411, found 634.2413.
2-(2-(4-甲氧基苯基)-2-(4-((3-氧代-1-苯基-3-(对甲苯基)丙基)氨基)苯基)乙基)丙二酸二甲酯(3f): 白色固体, 产率69%. m.p. 116.0~122.7 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.79 (d, J=8.4 Hz, 2H), 7.41 (d, J=7.2 Hz, 2H), 7.31 (t, J=7.6 Hz, 2H), 7.23 (d, J=8.4 Hz, 3H), 7.07 (d, J=8.8 Hz, 2H), 6.90 (d, J=8.4 Hz, 2H), 6.77 (d, J=8.4 Hz, 2H), 6.46 (d, J=8.4 Hz, 2H), 4.94~4.88 (m, 1H), 4.51 (s, 1H), 3.74 (s, 3H), 3.70 (t, J=8.0 Hz, 1H), 3.66 (d, J=2.4 Hz, 3H), 3.65 (d, J=1.2 Hz, 3H), 3.44 (dd, J=16.0, 4.8 Hz, 1H), 3.33 (dd, J=16.0, 8.0 Hz, 1H), 3.24 (td, J=7.2, 2.0 Hz, 1H), 2.55~2.48 (m, 2H), 2.39 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 197.9, 169.9, 158.0, 145.6, 144.3, 143.2, 136.2, 134.2, 132.8, 129.4, 128.8, 128.7, 128.4, 128.4, 127.3, 126.4, 114.0, 113.9, 55.2, 55.1, 52.5, 50.1, 47.0, 46.3, 34.9, 21.7; HRMS (ESI) calcd for C36H38NO6 (M＋H)＋ 580.2694, found 580.2691.
2-(2-(4-((3-(3-氯苯基)-3-氧代-1-苯丙基)氨基)苯基)-2-(4-甲氧基苯基)乙基)丙二酸二甲酯(3g): 无色油状物, 产率80%. 1H NMR (400 MHz, CDCl3) δ: 7.84 (t, J=2.0 Hz, 1H), 7.74 (d, J=7.6 Hz, 1H), 7.51 (d, J=8.0 Hz, 1H), 7.40 (d, J=7.2 Hz, 2H), 7.36 (t, J=8.0 Hz, 1H), 7.31 (t, J=7.6 Hz, 2H), 7.25~7.20 (m, 1H), 7.08 (d, J=8.8 Hz, 2H), 6.92 (d, J=8.4 Hz, 2H), 6.78 (d, J=8.4 Hz, 2H), 6.48 (d, J=8.4 Hz, 2H), 4.94 (t, J=6.4 Hz, 1H), 4.42 (s, 1H), 3.74 (s, 3H), 3.70 (d, J=6.8 Hz, 1H), 3.67 (d, J=2.0 Hz, 3H), 3.65 (d, J=0.8 Hz, 3H), 3.46~3.34 (m, 2H), 3.25 (td, J=7.2, 1.6 Hz, 1H), 2.57~2.47 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 196.9, 169.8, 169.9, 158.0, 145.4, 142.8, 138.2, 136.2, 135.1, 133.3, 133.0, 130.0, 128.9, 128.7, 128.5, 128.3, 127.5, 126.4, 126.3, 114.0, 113.9, 55.2, 54.8, 52.5, 50.1, 47.0, 46.4, 34.8; HRMS (ESI) calcd for C35H35NO6Cl (M＋H)＋ 600.2147, found 600.2146.
2-(2-(4-甲氧基苯基)-2-(4-((3-氧代-1-苯基-3-(间甲苯基)丙基)氨基)苯基)乙基)丙二酸二甲酯(3h): 无色油状物, 产率70%. 1H NMR (400 MHz, CDCl3) δ: 7.68 (d, J=5.6 Hz, 2H), 7.42 (d, J=7.2 Hz, 2H), 7.36 (d, J=7.8 Hz, 1H), 7.31 (t, J=8.0 Hz, 3H), 7.22 (t, J=7.2 Hz, 1H), 7.07 (d, J=8.4 Hz, 2H), 6.91 (d, J=8.4 Hz, 2H), 6.77 (d, J=8.4 Hz, 2H), 6.47 (d, J=8.4 Hz, 2H), 4.92 (dd, J=7.6, 5.2 Hz, 1H), 4.48 (s, 1H), 3.74 (s, 3H), 3.71 (d, J=8.0 Hz, 1H), 3.66 (d, J=2.0 Hz, 3H), 3.65 (d, J=1.2 Hz, 3H), 3.45 (dd, J=16.0, 5.2 Hz, 1H), 3.36 (dd, J=16.0, 7.6 Hz, 1H), 3.25 (td, J=7.2, 1.6 Hz, 1H), 2.52 (t, J=7.8 Hz, 2H), 2.37 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 198.4, 169.9, 169.9, 158.0, 145.6, 143.2, 138.5, 136.7, 136.2, 134.2, 132.8, 128.8, 128.8, 128.7, 128.5, 128.4, 127.3, 126.4, 125.4, 113.9, 113.9, 55.2, 55.0, 52.5, 50.1, 47.0, 46.5, 34.9, 21.3; HRMS (ESI) calcd for C36H38NO6 (M＋H)＋ 580.2694, found 580.2692.
2-(2-(4-((1-(4-氯苯基)-3-氧代-1-苯丙基)氨基)苯基)-2-(4-甲氧基苯基)乙基)丙二酸二甲酯(3i): 无色油状物, 产率94%. 1H NMR (400 MHz, CDCl3) δ: 7.88 (d, J=7.2 Hz, 2H), 7.56 (t, J=7.6 Hz, 1H), 7.44 (t, J=7.6 Hz, 2H), 7.36 (d, J=8.4 Hz, 2H), 7.29~7.25 (m, 2H), 7.07 (d, J=8.4 Hz, 2H), 6.92 (d, J=8.0 Hz, 2H), 6.78 (d, J=8.4 Hz, 2H), 6.44 (d, J=8.4 Hz, 2H), 4.91 (t, J=6.4 Hz, 1H), 4.49 (s, 1H), 3.74 (s, 3H), 3.70 (d, J=7.6 Hz, 1H), 3.67 (d, J=2.0 Hz, 3H), 3.66 (s, 3H), 3.47~3.33 (m, 2H), 3.25 (t, J=6.4 Hz, 1H), 2.52 (t, J=7.6 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 197.9, 169.9, 169.8, 158.0, 145.3, 141.7, 136.5, 136.1, 133.6, 133.2, 133.0, 129.0, 128.8, 128.7, 128.5, 128.2, 127.8, 114.0, 113.8, 55.2, 54.3, 52.5, 50.1, 47.0, 46.2, 34.9, 34.8; HRMS (ESI) calcd for C35H35NO6Cl (M＋H)＋ 600.2147, found 600.2144.
2-(2-(4-甲氧基苯基)-2-(4-((3-氧代-3-苯基-1-(对甲苯基)丙基)氨基)苯基)乙基)丙二酸二甲酯(3j): 无色油状物, 产率87%. 1H NMR (400 MHz, CDCl3) δ: 7.89 (d, J=7.2 Hz, 2H), 7.55 (t, J=7.2 Hz, 1H), 7.43 (t, J=7.6 Hz, 2H), 7.30 (d, J=8.0 Hz, 2H), 7.12 (d, J=7.6 Hz, 2H), 7.07 (d, J=8.8 Hz, 2H), 6.91 (d, J=8.4 Hz, 2H), 6.78 (d, J=8.8 Hz, 2H), 6.47 (d, J=8.4 Hz, 2H), 4.90 (dd, J=7.6, 5.2 Hz, 1H), 4.45 (s, 1H), 3.74 (s, 3H), 3.72~3.69 (m, 1H), 3.67 (d, J=1.6 Hz, 3H), 3.65 (s, 3H), 3.46 (dd, J=16.0, 5.2 Hz, 1H), 3.35 (dd, J=16.0, 7.6 Hz, 1H), 3.28~3.21 (m, 1H), 2.52 (t, J=7.6 Hz, 2H), 2.30 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 198.3, 169.9, 158.0, 145.6, 140.1, 134.0, 136.7, 136.3, 133.4, 132.7, 129.5, 128.7, 128.7, 128.4, 128.2, 126.3, 113.9, 113.9, 55.2, 54.7, 52.5, 50.1, 47.0, 46.5, 34.9, 31.5; HRMS (ESI) calcd for C36H38NO6 (M＋H)＋ 580.2694, found 580.2692.
2-(2-(4-甲氧基苯基)-2-(4-(1-(4-硝基苯基)-3-氧代- 3-苯丙基)氨基)苯基)乙基)丙二酸二甲酯(3k): 无色油状物, 产率64%. 1H NMR (400 MHz, CDCl3) δ: 8.17 (d, J=8.8 Hz, 2H), 7.89 (d, J=7.2 Hz, 2H), 7.59 (dd, J=17.2, 8.0 Hz, 3H), 7.45 (t, J=7.6 Hz, 2H), 7.07 (d, J=8.8 Hz, 2H), 6.93 (d, J=8.4 Hz, 2H), 6.78 (d, J=7.6 Hz, 2H), 6.43 (d, J=8.4 Hz, 2H), 5.04 (t, J=6.4 Hz, 1H), 4.59 (s, 1H), 3.74 (d, J=1.2 Hz, 3H), 3.73~3.69 (m, 1H), 3.67 (d, J=2.0 Hz, 3H), 3.66 (s, 3H), 3.47 (d, J=6.8 Hz, 2H), 3.23 (td, J=7.2, 2.0 Hz, 1H), 2.52 (td, J=7.6, 1.6 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 197.2, 169.8, 169.8, 158.1, 150.8, 147.3, 144.8, 136.3, 135.9, 133.8, 133.7, 128.9, 128.7, 128.6, 128.2, 127.5, 124.1, 114.0, 113.9, 55.2, 54.4, 52.5, 50.1, 47.0, 45.8, 34.8, 34.8; HRMS (ESI) calcd for C35H35N2O8 (M＋H)＋ 611.2388, found 611.2385.
2-(2-(4-甲氧基苯基)-2-(4-((1-(3-甲氧基苯基)-3-氧代-3-苯丙基)氨基)苯基)乙基)丙二酸二甲酯(3l): 无色油状物, 产率63%. 1H NMR (400 MHz, CDCl3) δ: 7.89 (d, J=7.2 Hz, 2H), 7.54 (d, J=7.4 Hz, 1H), 7.43 (t, J=7.8 Hz, 2H), 7.23 (t, J=8.0 Hz, 1H), 7.07 (d, J=8.4 Hz, 2H), 7.02~6.96 (m, 2H), 6.91 (d, J=8.4 Hz, 2H), 6.80~6.74 (m, 3H), 6.47 (d, J=8.4 Hz, 2H), 4.93~4.86 (m, 1H), 4.47 (s, 1H), 3.82 (dd, J=6.8, 2.4 Hz, 1H), 3.76 (s, 3H), 3.74 (s, 3H), 3.70 (d, J=8.0 Hz, 1H), 3.67 (d, J=2.0 Hz, 3H), 3.65 (s, 3H), 3.46 (dd, J=16.0, 4.8 Hz, 1H), 3.35 (dd, J=16.0, 8.0 Hz, 1H), 3.25 (t, J=6.4 Hz, 1H), 2.52 (t, J=7.2 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 198.2, 169.9, 169.9, 160.0, 158.0, 145.6, 145.0, 136.7, 136.2, 133.5, 132.9, 129.9, 128.7, 128.4, 128.2, 118.6, 114.3, 114.0, 113.9, 112.6, 112.2, 55.2, 55.0, 52.5, 50.1, 47.1, 46.4, 34.9, 34.9; HRMS (ESI) calcd for C36H38NO7 (M＋H)＋ 596.2643, found 596.2645.
2-(2-(4-((1-(3-溴苯基)-3-氧代-3-苯丙基)氨基)苯基)-2-(4-甲氧基苯基)乙基)丙二酸二甲酯(3m): 无色油状物, 产率71%. 1H NMR (400 MHz, CDCl3) δ: 7.72 (d, J=8.4 Hz, 2H), 7.56 (d, J=8.4 Hz, 2H), 7.39 (d, J=7.2 Hz, 2H), 7.30 (t, J=7.6 Hz, 2H), 7.22 (t, J=7.2 Hz, 1H), 7.07 (d, J=8.8 Hz, 2H), 6.91 (d, J=8.4 Hz, 2H), 6.78 (d, J=8.2 Hz, 2H), 6.47 (d, J=8.2 Hz, 2H), 4.95~4.89 (m, 1H), 4.49 (s, 1H), 3.74 (s, 3H), 3.70 (d, J=5.6 Hz, 1H), 3.66 (d, J=2.0 Hz, 3H), 3.65 (s, 3H), 3.41 (dd, J=16.4, 5.6 Hz, 1H), 3.35 (dd, J=16.0, 7.2 Hz, 1H), 3.25 (t, J=7.2 Hz, 1H), 2.52 (t, J=7.6 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 197.3, 169.9, 169.9, 158.0, 145.4, 142.9, 136.2, 136.2, 135.4, 133.0, 132.0, 130.1, 129.7, 128.9, 128.7, 128.7, 128.5, 127.5, 126.3, 114.0, 113.9, 55.2, 54.9, 52.5, 50.1, 47.0, 46.3, 34.9; HRMS (ESI) calcd for C35H35NO6Br (M＋H)＋ 644.1642, found 644.1645.
2-(2-(4-甲氧基苯基)-2-(4-((3-氧代-3-苯基-1-(邻甲苯基)丙基)氨基)苯基)乙基)丙二酸二甲酯(3n): 无色油状物, 产率86%. 1H NMR (400 MHz, CDCl3) δ: 7.90 (d, J=7.2 Hz, 2H), 7.55 (t, J=7.6 Hz, 1H), 7.43 (t, J=7.6 Hz, 3H), 7.19~7.13 (m, 3H), 7.08 (d, J=8.4 Hz, 2H), 6.91 (d, J=8.4 Hz, 2H), 6.78 (d, J=8.4 Hz, 2H), 6.42 (d, J=8.0 Hz, 2H), 5.18~5.12 (m, 1H), 4.36 (s, 1H), 3.74 (s, 3H), 3.70 (d, J=8.0 Hz, 1H), 3.67 (d, J=2.0 Hz, 3H), 3.65 (d, J=1.6 Hz, 3H), 3.42 (dd, J=16.4, 4.8 Hz, 1H), 3.33 (dd, J=16.4, 8.0 Hz, 1H), 3.26 (t, J=7.2 Hz, 1H), 2.53 (t, J=7.6 Hz, 2H), 2.48 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 198.4, 169.9, 158.0, 145.6, 145.6, 140.8, 136.7, 136.2, 134.8, 133.5, 132.7, 130.8, 128.7, 128.5, 128.2, 127.2, 126.7, 125.5, 113.9, 113.7, 55.2, 52.5, 51.1, 51.1, 50.1, 47.1, 44.6, 34.9, 34.9; HRMS (ESI) calcd for C36H38NO6 (M＋H)＋ 580.2694, found 580.2691.
2-(2-(2-溴-4-((1-(4-氯苯基)-3-氧代-3-苯丙基)氨基)- 5-甲基苯基)-2-(4-甲氧基苯基)乙基)丙二酸二甲酯(3o): 无色油状物, 产率86%. 1H NMR (400 MHz, CDCl3) δ: 7.88 (d, J=7.2 Hz, 2H), 7.55 (t, J=7.2 Hz, 1H), 7.43 (t, J=7.8 Hz, 2H), 7.39 (d, J=7.2 Hz, 2H), 7.32 (t, J=7.6 Hz, 2H), 7.25~7.21 (m, 1H), 7.11 (d, J=8.8 Hz, 2H), 6.97 (d, J=8.4 Hz, 1H), 6.79~6.72 (m, 3H), 6.46 (dd, J=8.0, 2.0 Hz, 1H), 4.91 (dd, J=7.6, 4.8 Hz, 1H), 4.60 (s, 1H), 4.27 (t, J=8.0 Hz, 1H), 3.73 (s, 3H), 3.67 (d, J=1.6 Hz, 3H), 3.65 (s, 3H), 3.46 (dd, J=16.4, 4.8 Hz, 1H), 3.37 (dd, J=16.4, 7.6 Hz, 1H), 3.27 (td, J=7.2, 3.2 Hz, 1H), 2.59~2.43 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 198.1, 169.8, 169.7, 158.1, 146.5, 142.5, 136.6, 135.1, 133.6, 131.1, 123.0, 128.9, 128.7, 128.6, 128.2, 127.6, 126.3, 125.6, 117.7, 113.8, 113.4, 55.2, 54.7, 52.5, 50.0, 46.2, 45.2, 34.7, 34.6; HRMS (ESI) calcd for C35H35NO6Br (M＋H)＋ 644.1642, found 644.1645.
2-(2-(4-甲氧基苯基)-2-(2-甲基-4-)((3-氧代-1,3-二苯丙基)氨基)苯基)乙基)丙二酸二甲酯(3p): 无色油状物, 产率86%. 1H NMR (400 MHz, CDCl3) δ: 7.90 (d, J=9.6 Hz, 2H), 7.58~7.53 (m, 1H), 7.47~7.40 (m, 4H), 7.32 (t, J=7.6 Hz, 2H), 7.23 (t, J=7.2 Hz, 1H), 7.04 (d, J=8.8 Hz, 2H), 6.98 (d, J=8.0 Hz, 1H), 6.76 (d, J=8.8 Hz, 2H), 6.38 (dd, J=7.6, 2.8 Hz, 2H), 4.98~4.92 (m, 1H), 4.36 (s, 1H), 3.92 (t, J=8.0 Hz, 1H), 3.74 (s, 3H), 3.67 (d, J=3.6 Hz, 3H), 3.66 (s, 3H), 3.48 (dd, J=16.0, 5.2 Hz, 1H), 3.38 (dd, J=16.0, 7.6 Hz, 1H), 3.33~3.27 (m, 1H), 2.48 (t, J=7.6 Hz, 2H), 2.07 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 198.3, 169.9, 157.9, 145.3, 143.3, 137.2, 136.7, 135.8, 133.4, 130.8, 129.0, 128.8, 128.7, 128.2, 127.3, 127.1, 126.4, 116.4, 113.8, 111.3, 55.2, 54.9, 52.5, 50.1, 46.4, 42.7, 35.1, 19.9; HRMS (ESI) calcd for C36H38NO6 (M＋H)＋ 580.2694, found 580.2696.
2-(2-(2-溴-4-((1-(4-氯苯基)-3-氧代-3-苯丙基)氨基)苯基)-2-(4-甲氧基苯基)乙基)丙二酸二甲酯(3q): 无色油状物, 产率86%. 1H NMR (400 MHz, CDCl3) δ: 7.88 (d, J=8.0 Hz, 2H), 7.57 (t, J=7.2 Hz, 1H), 7.44 (t, J=7.8 Hz, 2H), 7.34 (d, J=8.4 Hz, 2H), 7.28 (d, J=8.4 Hz, 2H), 7.12 (d, J=8.4 Hz, 2H), 6.99 (s, 1H), 6.80~6.75 (m, 2H), 6.72 (dd, J=2.4, 1.6 Hz, 1H), 6.43 (dd, J=8.4, 2.4 Hz, 1H), 4.88 (dd, J=7.2, 5.2 Hz, 1H), 4.62 (s, 1H), 4.28 (t, J=8.0 Hz, 1H), 3.74 (s, 3H), 3.69~3.64 (m, 6H), 3.46~3.32 (m, 2H), 3.27 (td, J=7.2, 2.8 Hz, 1H), 2.61~2.41 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 197.7, 169.7, 169.7, 158.1, 146.2, 141.0, 136.4, 134.9, 133.7, 133.2, 131.4, 129.1, 128.9, 128.9, 128.6, 128.6, 128.2, 125.6, 117.8, 113.8, 113.4, 55.2, 54.1, 52.6, 49.9, 46.0, 45.2, 34.7, 34.6; HRMS (ESI) calcd for C35H34BrClNO6 (M＋H)＋ 678.1253, found 678.1255.
2-(2-(2-((1-(4-氯苯基)-3-氧代-3-苯丙基)氨基) -5-甲基苯基)-2-(4-甲氧基苯基)乙基)丙二酸二甲酯(3r): 无色油状物, 产率40%. 1H NMR (400 MHz, CDCl3) δ: 7.95~7.88 (m, 1H), 7.88~7.83 (m, 1H), 7.54 (q, J=7.6 Hz, 1H), 7.43 (dt, J=12.0, 7.6 Hz, 2H), 7.37 (d, J=7.2 Hz, 1H), 7.29 (t, J=7.6 Hz, 1H), 7.23~7.17 (m, 1H), 7.15 (dd, J=8.4, 4.4 Hz, 3H), 7.08~6.99 (m, 1H), 6.86 (d, J=8.8 Hz, 1H), 6.84~6.74 (m, 3H), 6.37 (dd, J=18.0, 8.4 Hz, 1H), 5.03~4.96 (m, 1H), 4.64 (s, 1H), 3.95~3.86 (m, 1H), 3.78 (d, J=11.6 Hz, 3H), 3.68 (d, J=21.6 Hz, 3H), 3.62 (d, J=4.4 Hz, 3H), 3.47 (td, J=16.4, 8.0 Hz, 1H), 3.40~3.19 (m, 2H), 2.71~2.61 (m, 1H), 2.51~2.40 (m, 1H), 2.15 (d, J=8.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ: 203.1, 202.9, 175.7, 175.5, 175.3, 175.2, 163.9, 163.8, 148.9, 148.7, 147.5, 142.5, 142.4, 139.0, 138.9, 138.5, 135.1, 134.9, 134.1, 133.9, 134.0, 133.9, 133.6, 133.6, 133.4, 133.2, 133.1, 132.9, 132.5, 132.4, 131.9, 131.6, 131.5, 119.6, 119.6, 118.3, 118.1, 60.7, 60.6, 59.9, 59.7, 57.9, 57.9, 55.2, 55.1, 52.7, 52.3, 47.8, 47.7, 38.9, 38.6, 26.0, 26.0; HRMS (ESI) calcd for C36H37ClNO6 (M＋H)＋ 614.2304, found 614.2305.
2-(2-(2-甲氧基苯基)-2-(4-((3-氧代-1,3-二苯基丙基)氨基)苯基)乙基)丙二酸二甲酯(3s): 无色油状物, 产率37%. 1H NMR (400 MHz, CDCl3) δ: 7.89 (d, J=7.2 Hz, 2H), 7.54 (t, J=7.2 Hz, 1H), 7.45~7.39 (m, 4H), 7.30 (t, J=7.6 Hz, 2H), 7.22 (t, J=7.2 Hz, 1H), 7.12 (t, J=7.8 Hz, 2H), 6.96 (d, J=8.4 Hz, 2H), 6.85 (t, J=7.6 Hz, 1H), 6.78 (d, J=7.6 Hz, 1H), 6.46 (d, J=8.4 Hz, 2H), 4.96~4.91 (m, 1H), 4.43 (s, 1H), 4.25 (t, J=8.0 Hz, 1H), 3.72 (d, J=1.6 Hz, 3H), 3.65 (d, J=1.6 Hz, 3H), 3.61 (d, J=1.6 Hz, 3H), 3.46 (dd, J=15.6, 4.8 Hz, 1H), 3.37 (dd, J=16.0, 7.8 Hz, 1H), 3.28~3.22 (m, 1H), 2.59~2.45 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 198.3, 170.0, 169.9, 169.9, 156.9, 145.4, 143.2, 136.7, 133.4, 132.5, 132.4, 128.8, 128.7, 128.2, 127.7, 127.4, 127.2, 126.4, 120.6, 113.8, 110.7, 55.4, 55.0, 52.4, 50.3, 46.4, 40.0, 34.0; HRMS (ESI) calcd for C35H36NO6 (M＋H)＋ 566.2537, found 566.2538.
2-(2-(3,4-二甲氧基苯基)-2-(4-((3-氧代-1,3-二苯基丙基)氨基)苯基)乙基)丙二酸二甲酯(3t): 白色固体, m.p.110.2~118.0, 产率68%. 1H NMR (400 MHz, CDCl3) δ: 7.88 (d, J=7.2 Hz, 2H), 7.54 (t, J=7.6 Hz, 1H), 7.42 (dt, J=7.6, 4.0 Hz, 4H), 7.30 (t, J=7.6 Hz, 2H), 7.21 (t, J=7.2 Hz, 1H), 6.92 (d, J=8.4 Hz, 2H), 6.76~6.69 (m, 2H), 6.65 (t, J=2.0 Hz, 1H), 6.48 (d, J=7.6 Hz, 2H), 4.95 (dd, J=7.7, 5.1 Hz, 1H), 4.50 (s, 1H), 3.81 (s, 3H), 3.79 (d, J=2.4 Hz, 3H), 3.71 (t, J=9.1 Hz, 1H), 3.66 (d, J=2.4 Hz, 3H), 3.65 (d, J=1.2 Hz, 3H), 3.46 (dd, J=16.0, 5.2 Hz, 1H), 3.38 (dd, J=16.0, 7.6 Hz, 1H), 3.26 (td, J=7.2, 2.0 Hz, 1H), 2.57~2.47 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 198.2, 169.9, 169.9, 148.8, 147.5, 145.7, 143.1, 136.7, 133.5, 132.7, 128.8, 128.7, 128.4, 128.2, 127.4, 126.4, 119.6, 113.9, 111.3, 111.2, 55.9, 55.8, 54.9, 52.5, 50.1, 47.5, 46.4, 34.9, 34.8; HRMS (ESI) calcd for C36H38NO7 (M＋H)＋ 596.2643, found 596.2645.
2-(2-(2,3,4-二甲氧基苯基)-2-(4-((3-氧代-1,3-二苯基丙基)氨基)苯基)乙基)丙二酸二甲酯(3u): 无色油状物, 产率72%. 1H NMR (400 MHz, CDCl3) δ: 7.88 (d, J=7.2 Hz, 2H), 7.54 (t, J=7.2 Hz, 1H), 7.44~7.38 (m, 4H), 7.32~7.27 (m, 2H), 7.21 (t, J=6.8 Hz, 1H), 6.94 (d, J=8.4 Hz, 2H), 6.87 (dd, J=8.8, 2.0 Hz, 1H), 6.59 (dd, J=8.8, 1.6 Hz, 1H), 6.47 (d, J=8.4 Hz, 2H), 4.94 (ddd, J=7.2, 5.2, 1.2 Hz, 1H), 4.46 (s, 1H), 4.11 (t, J=8.0 Hz, 1H), 3.80 (s, 3H), 3.80 (s, 3H), 3.67 (d, J=2.0 Hz, 3H), 3.63 (s, 3H), 3.60 (d, J=4.0 Hz, 3H), 3.49~3.35 (m, 2H), 3.28 (t, J=7.2 Hz, 1H), 2.55~2.42 (m, 2H); 13C NMR (101 MHz, CDCl3) δ: 198.3, 167.0, 169.9, 152.1, 151.7, 145.4, 143.1, 142.3, 136.7, 133.4, 132.8, 130.2, 128.8, 128.7, 128.2, 127.3, 126.4, 121.7, 114.0, 113.9, 107.1, 60.7, 60.6, 55.9, 55.0, 52.5, 52.4, 50.2, 46.4, 40.4, 40.4, 34.4; HRMS (ESI) calcd for C37H40NO8 (M＋H)＋ 626.2748, found 626.2745.
2-(2-(4-甲氧基苯基)-2-(4-((3-氧代-1-苯基-3-噻吩基)丙基)氨基)苯基)乙基)丙二酸二甲酯(3v): 无色油状物, 产率80%.1H NMR (400 MHz, CDCl3) δ: 7.95 (d, J=1.6 Hz, 1H), 7.48 (d, J=5.2 Hz, 1H), 7.40 (d, J=7.2 Hz, 2H), 7.33~7.26 (m, 3H), 7.22 (t, J=7.2 Hz, 1H), 7.07 (d, J=8.8 Hz, 2H), 6.91 (d, J=8.6 Hz, 2H), 6.77 (d, J=8.4 Hz, 2H), 6.46 (d, J=8.4 Hz, 2H), 4.92~4.87 (m, 1H), 4.52 (s, 1H), 3.73 (s, 3H), 3.69 (s, 1H), 3.66 (d, J=2.4 Hz, 3H), 3.64 (d, J=1.2 Hz, 3H), 3.34 (dd, J=15.6, 5.2 Hz, 1H), 3.28 (dd, J=7.2, 4.4 Hz, 1H), 3.24 (td, J=7.4, 2.7 Hz, 1H), 2.52 (td, J=7.7, 1.8 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 192.4, 169.9, 158.0, 145.6, 143.1, 142.1, 136.2, 132.8, 132.6, 128.9, 128.7, 128.4, 127.4, 126.9, 126.7, 126.3, 113.9, 113.9, 55.2, 55.2, 52.5, 50.1, 47.7, 47.0, 34.9, 34.9; HRMS (ESI) calcd for C33H34NO6S (M＋H)＋ 572.2102, found 572.2104.
2-(2-(4-甲氧基苯基)-2-(4-((3-氧代-1-苯基-3-甲基基)丙基)氨基)苯基)乙基)丙二酸二甲酯(3w): 无色油状物, 产率98%. 1H NMR (400 MHz, CDCl3) δ: 7.35~7.28 (m, 4H), 7.22 (t, J=7.2 Hz, 1H), 7.08 (d, J=8.4 Hz, 2H), 6.92 (d, J=8.4 Hz, 2H), 6.78 (d, J=7.6 Hz, 2H), 6.46 (d, J=8.4 Hz, 2H), 4.77 (t, J=6.6 Hz, 1H), 4.36 (s, 1H), 3.74 (s, 3H), 3.69 (s, 1H), 3.66 (d, J=2.8 Hz, 3H), 3.65 (d, J=1.6 Hz, 3H), 3.25 (td, J=7.2, 2.0 Hz, 1H), 2.88 (d, J=6.4 Hz, 2H), 2.52 (t, J=7.6 Hz, 2H), 2.08 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 207.1, 169.9, 169.8, 158.0, 145.4, 142.7, 136.2, 132.9, 128.8, 128.7, 128.5, 127.4, 126.3, 113.9, 55.2, 54.5, 52.5, 51.3, 50.1, 47.1, 34.9, 34.9, 30.7; HRMS (ESI) calcd for C30H34NO6 (M＋H)＋ 504.2381, found 504.2388.
3.2.3 化合物5a的合成
向15 mL的反应管中加入苄基苯胺4a (0.2 mmol, 1.0 equiv.)和D-A环丙烷2a (0.5 mmol, 2.5 equiv.), Yb(OTf)3 (0.1 mmol, 0.5 equiv.), 随后加入2.0 mL乙腈溶剂, 最将反应混合物在室温下反应0.5 h. 待反应完成后, TLC检测基本无苄基苯胺剩余后, 减压蒸馏除去溶剂, 粗产品在硅胶柱(200~300目, 石油醚/乙酸乙酯, V∶V=5∶1)上进行柱层析纯化, 得到2-(2-(苄基(苯基)氨基)-2-(4-甲氧基苯基)乙基)丙二酸二甲酯(5a), 无色油状物, 产率54%. 1H NMR (400 MHz, CDCl3) δ: 7.22~7.11 (m, 9H), 6.83 (td, J=6.4, 1.6 Hz, 4H), 6.77~6.72 (m, 1H), 5.09 (t, J=7.6 Hz, 1H), 4.31~4.17 (m, 2H), 3.77 (s, 3H), 3.69 (s, 3H), 3.66 (s, 3H), 3.63 (t, J=7.2 Hz, 1H), 2.59 (dd, J=8.0, 6.8 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ: 169.8, 169.7, 158.9, 149.3, 139.2, 131.3, 129.1, 128.9, 128.3, 126.9, 126.5, 118.5, 116.2, 113.8, 60.4, 52.7, 52.6, 49.7, 49.0, 31.0; HRMS (ESI) calcd for C27H30NO5 (M＋H)＋ 448.2119, found 448.2115.
致谢 感谢石河子大学分析测试中心赵吉星老师在单晶结构分析上给予的帮助.
辅助材料(Supporting Information) 所有合成化合物的核磁共振(NMR)谱图及化合物3f的单晶数据. 这些材料可以免费从本刊网站(http://sioc-journal.cn/)上下载.
(Zhao, C.)