1,3-二苯基丙-2-烯-1-酮俗称查尔酮. 官能化的查尔酮衍生物具有抗菌、抗真菌、抗结核、抗氧化、抗疟疾、抗癌、抗炎、抗黄疸和抗丝虫等生物活性[1], 已经发展成为药物化学中的一类优势结构[2]. 官能化查尔酮还是重要的有机合成原料, 在有机合成中有着广泛的应用[3]. 因此, 官能化查尔酮的合成得到了人们的重视[4]. 查尔酮的合成方法主要有芳香酮与芳香醛的羟醛缩合[5]、芳香酮与苄胺的氧化缩合[6]、芳基卤化物和炔丙醇之间的Sonogashira偶联[7]、芳基卤化物与芳基烯间的羰基化Heck偶联[8]、芳酮与芳烃或芳基羧酸的交叉偶联[9]及芳基内炔与芳醛的偶联[10]等. Jiang等[11]利用高分子负载的三芳基膦催化二苯基丙炔酮与丙二酸二乙酯的加成得到α-位二(乙氧羰基)甲基取代的查尔酮, 但产率不高(47%, Scheme 1, a); Srinivasan等[12]利用TiCl4促进的cis-2-苯甲酰基-3-苯基环丙烷-1,1-二羧酸二乙酯的开环异构化, 以较高产率得到α-[二(乙氧羰基)甲基]查尔酮(82%, Scheme 1, b), 但原料不易得. 本文将报道在氢化钠作用下芳甲基对甲基苯基砜(1)和2-芳甲酰基甲亚基丙二酸酯(2)的反应, 高效率地得到一系列α-[二(烷氧羰基)甲基]查尔酮(Scheme 1, c).
1 结果与讨论
1.1 α-[二(烷氧羰基)甲基]查尔酮的制备
在前期工作基础上[13], 考察氢化钠作用下苄基对甲基苯基砜(1a)和2-苯甲酰基甲亚基丙二酸二乙酯(2a)反应的最优条件, 结果见表1. 将1.5 equiv. 1a(以化合物2a为参照计量)与2.5 equiv.氢化钠混合于无水N,N-二甲基甲酰胺(DMF)中, 在室温下反应一段时间(约0.5 h), 加入2-苯甲酰基甲亚基丙二酸二乙酯(2a), 搅拌12 h后薄层色谱(TLC)显示没有新化合物生成(表1, Entry 1). 在40 ℃下反应10 h, 可以66%的产率分离得到α-[二(乙氧羰基)甲基]查尔酮(3aa)(表1, Entry 2). 在60 ℃下反应6 h, 分离产率高达84%(表1, Entry 3). 继续升温至80 ℃, 3aa的产率下降, 反应体系比较复杂(表1, Entry 4). 减少或增加氢化钠的用量, 反应情况没有改善(表1, Entries 5, 6), 分离到副产物2-苯甲酰基丙烷-1,1,3,3-四羧酸四乙酯(3'aa). 考察溶剂的影响发现, 在二甲亚砜(DMSO)中反应, 3aa的分离产率得到进一步提高(表1, Entry 8). 1a的用量降至1.1 equiv.时, 3aa的分离产率明显下降(表1, Entry 9).
表1 苄基对甲基苯基砜(1a)与2-苯甲酰基甲亚基丙二酸二乙酯(2a)反应条件的优化aTable 1 Optimization of reaction conditions for 2-benzoylmethylenemalonate (2a) with benzyl p-tolyl sulfone (1a)  |
| Entry | TsBn/equiv. | NaH/equiv. | Solvent | Temperature/℃ | Timeb/h | Yieldc/% of 3aa |
|---|---|---|---|---|---|---|
| 1 | 1.5 | 2.5 | DMF | 25 | 12 | NR |
| 2 | 1.5 | 2.5 | DMF | 40 | 10 | 66 |
| 3 | 1.5 | 2.5 | DMF | 60 | 6 | 84 |
| 4 | 1.5 | 2.5 | DMF | 80 | 3 | 67 |
| 5 | 1.5 | 2.0 | DMF | 60 | 24 | 58 |
| 6 | 1.5 | 3.0 | DMF | 60 | 5 | 62d |
| 7 | 1.5 | 2.5 | THF | 60 | 6 | 78 |
| 8 | 1.5 | 2.5 | DMSO | 60 | 12 | 90 |
| 9 | 1.1 | 2.5 | DMSO | 60 | 14 | 85 |
a The reaction was conducted with 0.3 mmol of 2a. b Determined by TLC monitoring. c Isolated yield. d By-product 3'aa was isolated concurrently in 10% yield. |
在优化的反应条件下考察反应的底物适用性(表2). 2-酰基甲亚基丙二酸二酯2中酯基氧原子上的烃基几乎没有影响(3aa~3ac). R1为各种取代的苯基时大多具有很好的兼容性(3ad~3ak), R1为强吸电子基取代的苯基时产率稍低(3al, 3an, 3ao), R1为邻硝基苯基时反应体系复杂, 未能分离出纯的标题化合物(3am), R1为噻吩-2-基时产率中等(3ap), R1为甲基时产率很低且杂有1a (3aq). 2-氰基-2-苯甲酰甲亚基乙酸乙酯(2r)和2-苯甲酰甲亚基丙二腈(2s)与1a的反应体系复杂, 未能分离出纯的标题化合物(3ar和3as). 烃基对甲基苯基砜1中R2为各种取代的苯基时具有较好反应性(3ba~3ia和3ka), R2为邻硝基苯基或对硝基苯基时反应体系复杂, 未能分离出纯的目标化合物(3ja和3la). R2为呋喃-2-基时的产率很高(3ma), R2为甲基时的反应体系非常复杂, 未能分离出纯的目标化合物(3na). 产物3ab的结构得到X射线单晶衍射分析的确证. 5 mmol (1.381 g) 2a在标准条件下的实验表明该反应有好的实用性(3aa).
表2 α-[二(烷氧羰基)甲基]查尔酮(3)的制备a,bTable 2 Preparation of α-(di(alkoxycarbonyl)methyl)chalcones (3)  |
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a The reaction was conducted with 0.3 mmol of 2. b Isolated yield. c Yield obtained from a 5 mmol scale experiment. d A complicated reaction mixture was obtained, and the titled compound was not isolated. e Determined by 1H NMR analysis, and a mixture of 3aq and 1a was obtained. f A complicated reaction mixture was obtained, and the 1a was recovered. |
1.2 α-[二(烷氧羰基)甲基]查尔酮的环丙烷化
表3 三甲基碘化亚砜与3aa反应条件的优化aTable 3 Optimization of reaction conditions for 3aa with trimethylsulfoxonium iodide  |
| Entry | OS＋(CH3)3I− /equiv. | NaH/equiv. | Solvent | Temperature/℃ | Timeb/h | Yieldc/% of 4a | drd |
|---|---|---|---|---|---|---|---|
| 1 | 2.0 | 3.0 | DMF | 40 | 96 | 78 | 96∶4 |
| 2 | 2.0 | 3.0 | DMF | 50 | 48 | 88 | 94∶6 |
| 3 | 2.0 | 3.0 | DMF | 60 | 37 | 80 | 87∶13 |
| 4 | 1.5 | 3.0 | DMF | 50 | 52 | 40 | 75∶25 |
| 5 | 2.5 | 3.0 | DMF | 50 | 72 | 45 | 90∶10 |
| 6 | 2.0 | 2.5 | DMF | 50 | 96 | 42 | 91∶9 |
| 7 | 2.0 | 3.5 | DMF | 50 | 30 | 75 | 80∶20 |
| 8 | 2.0 | 3.0 | DMSO | 50 | 48 | 82 | 89∶11 |
| 9 | 2.0 | 3.0 | THF | 50 | 78 | 63 | 88∶12 |
a The reaction was conducted with 0.3 mmol of 3aa. b Determined by TLC monitoring. c Isolated yield. d Determined by 1H NMR. |
将2.0 equiv.三甲基碘化亚砜, 3.0 equiv.氢化钠和3aa混合于无水DMF中, 在40 ℃下反应96 h, 以96∶4的非对映选择性和78%的分离产率得到环丙烷衍生物4a(表3, Entry 1). 在50 ℃下反应时间大大缩短, 产率有明显提高但非对映选择性略有下降(表3, Entry 2). 继续升高温度, 反应体系变复杂, 4a的产率及非对映选择性显著降低(表3, Entry 3). 减少或增加三甲基碘化亚砜的用量(表3, Entries 4, 5), 减少或增加氢化钠的用量(表3, Entries 6, 7), 反应情况都没有改善. 改变溶剂也没有得到更好的结果(表3, Entries 8, 9).
各种α-[二(烷氧羰基)甲基]查尔酮3与三甲基碘化亚砜在最优条件下的反应结果总结于表4. α-[二(烷氧羰基)甲基]查尔酮(3)中酯基氧原子上的烃基对反应几乎没有影响(4a~4c), 芳甲酰基芳环(Ar1)上取代基(4d~4l)及杂环芳基(4o)、芳环(Ar2)上取代基(4p~4w)及杂环芳基(4y)大多具有较好的兼容性, 芳甲酰基芳环(Ar1)及芳环(Ar2)上有强吸电子的硝基时(4m, 4n, 4x), 反应体系复杂, 未能分离得到相应的环丙烷衍生物. 产物4a的结构得到X射线单晶衍射分析的确证. 4 mmol 3aa (1.466 g)在最优条件下的克级规模实验显示该反应有好的实用性(表4, 4a).
表4 多取代环丙烷衍生物4的合成a,bTable 4 Synthesis of the multisubstituted cyclopropanes 4  |
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a The reaction was conducted with 0.3 mmol of 3. b Isolated yield. c Yield obtained from a 4 mmol scale experiment. d A complicated reaction mixture was obtained, and the target compound was not isolated. |
1.3 可能的反应机理
α-[二(烷氧羰基)甲基]查尔酮3的制备及其环丙烷化反应的可能机理见Scheme 2. 在NaH存在下, 芳甲基对甲基苯基砜1形成的碳负离子与2-芳甲酰基甲亚基丙二酸二酯2的共轭加成形成中间体I, 经1,2-质子转移得中间体II, II消除Ts－得α-[二(烷氧羰基)甲基]查尔酮3. Ts－是好的离去基团, 中间体I没有发生环丙烷化的原因可能是共轭结构的查尔酮衍生物3更稳定. Corey叶立德与3发生共轭加成得中间体III, III发生分子内亲核取代而环丙烷化, 生成产物4. 反应的高立体选择性可能受1,3-烯丙位张力控制[17], 原子半径最小的烯丙位氢原子与烯键1-位碳原子上的芳基(Ar1)位于同侧时张力最小. II为发生消除生成3的优势构象, III为发生环丙烷化生成4的优势构象.
1.4 环丙烷衍生物的反应初探
2 结论
在氢化钠作用下, 芳甲基对甲基苯基砜1与2-芳甲酰基甲亚基丙二酸酯2反应, 经亲核加成/1,2-质子转移/消除过程, 以中等到好的产率制得α-[二(烷氧羰基)甲基]查尔酮3. 利用制得的查尔酮3与Corey叶立德反应, 经亲核加成/环丙烷化过程, 以好的产率合成得到多取代环丙烷衍生物4. 初步研究发现该环丙烷衍生物4可在无催化剂存在下与乌洛托品或1,3,5-三苯基-1,3,5-三嗪烷发生环缩合反应. 我们实验室正在进一步研究此类环丙烷的合成应用潜力.
3 实验部分
3.1 仪器与试剂
用XT4A型显微熔点测定仪测定化合物的熔点, 温度计未经校正; 用Bruker Avance 500或400型谱仪测定化合物的核磁共振谱, 以CDCl3为溶剂、TMS为内标; 用Agilent 6100B测定化合物的质谱.
3.2 实验方法
3.2.1 α-[二(烷氧羰基)甲基]查尔酮3的合成
在经无水无氧处理过的反应管中加4.5 mmol芳甲基对甲基苯基砜1, 20 mL无水DMSO和7.5 mmol氢化钠(质量分数为60%), 于室温下搅拌0.5 h, 再加入3 mmol 2-芳甲酰基甲亚基丙二酸二酯2, 然后将该反应管置于60 ℃的金属浴中搅拌反应, TLC跟踪至化合物2消失, 冷却至室温并加入30 mL饱和氯化铵水溶液淬灭反应, 用乙酸乙酯萃取(100 mL×3), 合并有机相, 用饱和氯化钠水溶液洗涤有机相(20 mL×3), 无水硫酸钠干燥, 过滤, 回收乙酸乙酯, 柱层析分离得到纯的产物3.
(E)-2-(3-氧代-1,3-二苯基丙-1-烯-2-基)丙二酸二乙酯(3aa)[11-12,20]: 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得黄色油状液体, 产率90%. 1H NMR (CDCl3, 500 MHz) δ: 7.90~7.82 (m, 2H), 7.61~7.54 (m, 1H), 7.51~7.45 (m, 2H), 7.44~7.34 (m, 6H), 4.88 (s, 1H), 4.30~4.16 (m, 4H), 1.25 (t, J=7.1 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 196.7, 167.7, 144.1, 137.5, 134.4, 134.3, 132.2, 129.9, 129.2, 128.8, 128.3, 61.9, 51.5, 14.0; HRMS (ESI) calcd for C22H23O5 [M＋H]＋ 367.1540, found 367.1548.
2-苯甲酰基丙烷-1,1,3,3-四羧酸四乙酯(3'aa)[21]: 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得黄色油状液体, 产率10%. 1H NMR (CDCl3, 500 MHz) δ: 8.07~7.98 (m, 2H), 7.60~7.52 (m, 1H), 7.50~7.42 (m, 2H), 4.85 (t, J=8.0 Hz, 1H), 4.23~4.12 (m, 4H), 4.06 (d, J=8.0 Hz, 2H), 4.03~3.90 (m, 4H), 1.23 (t, J=7.2 Hz, 6H), 1.10 (t, J=7.2 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 199.0, 167.9, 167.7, 136.9, 133.4, 129.1, 128.6, 62.0, 52.9, 43.8, 14.0, 13.8.
(E)-2-(3-氧代-1,3-二苯基丙-1-烯-2-基)丙二酸二甲酯(3ab): 柱层析[V(石油醚)∶V(乙酸乙酯)=10∶1]分离得黄色固体, 产率87%. m.p. 114~115 ℃; 1H NMR (CDCl3, 500 MHz) δ: 7.89~7.81 (m, 2H), 7.61~7.54 (m, 1H), 7.51~7.46 (m, 2H), 7.45~7.35 (m, 6H), 4.92 (s, 1H), 3.77 (s, 6H); 13C NMR (125 MHz, CDCl3) δ: 196.7, 168.2, 144.4, 137.4, 134.2, 134.1, 132.3, 129.9, 129.4, 128.9, 128.8, 128.4, 53.0, 51.1; HRMS (ESI) calcd for C20H19O5 [M＋H]＋ 339.1227, found 339.1226.
(E)-2-(3-氧代-1,3-二苯基丙-1-烯-2-基)丙二酸二异丙酯(3ac): 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得黄色油状液体, 产率88%. 1H NMR (500 MHz, CDCl3) δ: 7.91~7.82 (m, 2H), 7.60~7.52 (m, 1H), 7.50~7.33 (m, 8H), 5.18~5.05 (m, 2H), 4.82 (s, 1H), 1.28 (d, J=6.3 Hz, 6H), 1.23 (d, J=6.3 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 196.4, 167.1, 143.7, 137.6, 134.7, 134.5, 134.2, 132.0, 129.7, 129.1, 128.8, 128.7, 128.1, 69.4, 51.8, 21.5; HRMS (ESI) calcd for C24H27O5 [M＋H]＋ 395.1853, found 395.1858.
(E)-2-(3-(4-氟苯基)-3-氧代-1-苯基丙-1-烯-2-基)丙二酸二乙酯(3ad): 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得黄色油状液体, 产率87%. 1H NMR (500 MHz, CDCl3) δ: 7.86~7.84 (m, 2H), 7.48~7.36 (m, 5H), 7.33 (s, 1H), 7.20~7.12 (m, 2H), 4.88 (s, 1H), 4.33~4.15 (m, 4H), 1.25 (t, J=7.1 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 195.3, 167.7, 165.3 (d, 1JFC=253.7 Hz), 143.5, 134.3, 134.1, 133.7 (d, 4JFC=2.8 Hz), 132.5 (d, 3JFC=9.1 Hz), 129.3, 128.9, 128.8, 115.5 (d, 2JFC=21.9 Hz), 62.0, 51.5, 14.0; 19F NMR (470 MHz, CDCl3) δ: －106.3; HRMS (ESI) calcd for C22H22FO5 [M＋H]＋ 385.1446, found 385.1451.
(E)-2-(3-(4-氯苯基)-3-氧代-1-苯基丙-1-烯-2-基)丙二酸二乙酯(3ae): 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得黄色固体, 产率92%. m.p. 71~72 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.87~7.76 (m, 2H), 7.50~7.36 (m, 7H), 7.33 (s, 1H), 4.88 (s, 1H), 4.32~4.14 (m, 4H), 1.26 (t, J=7.2 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 195.5, 167.7, 143.9, 138.7, 135.8, 134.2, 134.0, 131.3, 129.4, 128.9, 128.8, 128.7, 62.0, 51.4, 14.0; HRMS (ESI) calcd for C22H22ClO5 [M＋H]＋ 401.1150, found 401.1147.
(E)-2-(3-(4-溴苯基)-3-氧代-1-苯基丙-1-烯-2-基)丙二酸二乙酯(3af): 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得黄色油状液体, 产率91%. 1H NMR (500 MHz, CDCl3) δ: 7.80~7.68 (m, 2H), 7.67~7.58 (m, 2H), 7.48~7.36 (m, 5H), 7.33 (s, 1H), 4.87 (s, 1H), 4.32~4.14 (m, 4H), 1.26 (t, J=7.1 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 195.7, 167.6, 144.0, 136.3, 134.2, 134.0, 131.6, 131.4, 129.4, 128.9, 128.8, 127.3, 62.0, 51.4, 14.0; HRMS (ESI) calcd for C22H22BrO5 [M＋H]＋ 445.0645, found 445.0642.
(E)-2-(3-氧代-1-苯基-3-(p-甲基苯基)丙-1-烯-2-基)丙二酸二乙酯(3ag): 柱层析[V(石油醚)∶V(乙酸乙 酯)=15∶1]分离得黄色油状液体, 产率88%. 1H NMR (500 MHz, CDCl3) δ: 7.83~7.72 (m, 2H), 7.48~7.33 (m, 6H), 7.31~7.26 (m, 2H), 4.87 (s, 1H), 4.32~4.13 (m, 4H), 2.43 (s, 3H), 1.26 (t, J=7.1 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 196.4, 167.8, 143.5, 143.0, 134.8, 134.4, 130.1, 129.1, 129.0, 128.8, 61.9, 51.6, 21.6, 14.0; HRMS (ESI) calcd for C23H25O5 [M＋H]＋ 381.1697, found 381.1695.
(E)-2-(3-(2-甲氧基苯基)-3-氧代-1-苯基丙-1-烯-2-基)丙二酸二乙酯(3ah): 柱层析[V(石油醚)∶V(乙酸乙酯)=10∶1]分离得黄色油状液体, 产率85%. 1H NMR (500 MHz, CDCl3) δ: 7.50~7.30 (m, 8H), 7.05~6.94 (m, 2H), 4.81 (s, 1H), 4.29~4.11 (m, 4H), 3.83 (s, 3H), 1.25 (t, J=7.1 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 196.0, 167.7, 157.4, 146.7, 135.8, 134.5, 131.7, 129.9, 129.3, 128.9, 128.6, 128.1, 120.3, 111.6, 61.7, 55.8, 50.7, 14.0; HRMS (ESI) calcd for C23H25O6 [M＋H]＋ 397.1646, found 397.1649.
(E)-2-(3-(3-甲氧基苯基)-3-氧代-1-苯基丙-1-烯-2-基)丙二酸二乙酯(3ai): 柱层析[V(石油醚)∶V(乙酸乙酯)=12∶1]分离得黄色油状液体, 产率86%. 1H NMR (500 MHz, CDCl3) δ: 7.47~7.33 (m, 9H), 7.15~7.08 (m, 1H), 4.87 (s, 1H), 4.31~4.15 (m, 4H), 3.85 (s, 3H), 1.25 (t, J=7.1 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 196.4, 167.7, 159.6, 144.2, 138.8, 134.33, 134.26, 129.24, 129.21, 128.8, 122.6, 118.7, 114.2, 61.9, 55.4, 51.5, 14.0; HRMS (ESI) calcd for C23H25O6 [M＋H]＋ 397.1646, found 397.1645.
(E)-2-(3-(4-甲氧基苯基)-3-氧代-1-苯基丙-1-烯-2-基)丙二酸二乙酯(3aj): 柱层析[V(石油醚)∶V(乙酸乙酯)=10∶1]分离得黄色固体, 产率86%. m.p. 95~96 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.94~7.84 (m, 2H), 7.46~7.35 (m, 6H), 7.34 (s, 1H), 7.00~6.93 (m, 2H), 4.87 (s, 1H), 4.31~4.13 (m, 4H), 3.87 (s, 3H), 1.24 (t, J=7.2 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 195.4, 167.8, 163.1, 142.5, 134.4, 134.2, 132.3, 129.9, 129.0, 128.8, 128.7, 113.6, 61.8, 55.5, 51.7, 13.9; HRMS (ESI) calcd for C23H25O6 [M＋H]＋ 397.1646, found 397.1643.
(E)-2-(3-(3,4-二甲氧基苯基)-3-氧代-1-苯基丙-1-烯- 2-基)丙二酸二乙酯(3ak): 柱层析[V(石油醚)∶V(乙酸乙酯)=2∶1]分离得黄色油状液体, 产率87%. 1H NMR (500 MHz, CDCl3) δ: 7.53 (dd, J=8.3, 1.9 Hz, 1H), 7.48 (d, J=1.9 Hz, 1H), 7.46~7.34 (m, 6H), 6.91 (d, J=8.4 Hz, 1H), 4.87 (s, 1H), 4.32~4.13 (m, 4H), 3.95 (s, 3H), 3.93 (s, 3H), 1.24 (t, J=7.1 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 195.4, 167.8, 152.9, 149.0, 142.5, 134.4, 134.1, 130.0, 129.1, 128.79, 128.75, 125.0, 112.1, 109.8, 61.9, 56.1, 56.0, 51.7, 14.0; HRMS (ESI) calcd for C24H27O7 [M＋H]＋ 427.1751, found 427.1749.
(E)-2-(3-氧代-1-苯基-3-(4-(三氟甲基)苯基)丙-1-烯- 2-基)丙二酸二乙酯(3al): 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得黄色油状液体, 产率71%. 1H NMR (500 MHz, CDCl3) δ: 7.94 (d, J=8.0 Hz, 2H), 7.74 (d, J=8.1 Hz, 2H), 7.48~7.37 (m, 5H), 7.34 (s, 1H), 4.89 (s, 1H), 4.33~4.16 (m, 4H), 1.27 (t, J=7.1 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 195.7, 167.6, 144.9, 140.8, 134.3, 133.9, 133.6 (q, 2JFC=32.6 Hz), 130.1, 129.6, 128.94, 128.88, 125.4 (q, 3JFC=3.6 Hz), 123.7 (q, 1JFC=272.8 Hz), 62.1, 51.4, 14.0; 19F NMR (470 MHz, CDCl3) δ: －63.0; HRMS (ESI) calcd for C23H22F3O5 [M＋H]＋ 435.1414, found 435.1422.
(E)-2-(3-(3-硝基苯基)-3-氧代-1-苯基丙-1-烯-2-基)丙二酸二乙酯(3an): 柱层析[V(石油醚)∶V(乙酸乙 酯)=10∶1]分离得黄色油状液体, 产率76%. 1H NMR (500 MHz, CDCl3) δ: 8.72~8.64 (m, 1H), 8.46~8.40 (m, 1H), 8.22~8.15 (m, 1H), 7.74~7.66 (m, 1H), 7.50~7.39 (m, 5H), 7.33 (s, 1H), 4.90 (s, 1H), 4.34~4.17 (m, 4H), 1.28 (t, J=7.1 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 194.4, 167.5, 148.1, 144.5, 139.0, 135.4, 134.0, 133.6, 129.7, 129.6, 129.0, 128.9, 126.6, 124.7, 62.1, 51.4, 14.0; HRMS (ESI) calcd for C22H22NO7 [M＋H]＋ 412.1391, found 412.1388.
(E)-2-(3-(4-硝基苯基)-3-氧代-1-苯基丙-1-烯-2-基)丙二酸二乙酯(3ao): 柱层析[V(石油醚)∶V(乙酸乙 酯)=12∶1]分离得黄色油状液体, 产率73%. 1H NMR (500 MHz, CDCl3) δ: 8.39~8.30 (m, 2H), 8.03~7.94 (m, 2H), 7.48~7.37 (m, 5H), 7.31 (s, 1H), 4.90 (s, 1H), 4.33~4.19 (m, 4H), 1.28 (t, J=7.1 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 195.0, 167.5, 149.8, 145.3, 143.0, 134.3, 133.6, 130.6, 129.8, 129.0, 128.9, 123.6, 62.1, 51.2, 14.0; HRMS (ESI) calcd for C22H22NO7 [M＋H]＋ 412.1391, found 412.1398.
(E)-2-(3-氧代-1-苯基-3-(噻吩-2-基)丙-1-烯-2-基)丙二酸二乙酯(3ap): 柱层析[V(石油醚)∶V(乙酸乙酯)=5∶1]分离得黄色油状液体, 产率61%. 1H NMR (CDCl3, 500 MHz) δ: 7.76 (dd, J=3.8, 1.0 Hz, 1H), 7.69 (dd, J=4.9, 1.0 Hz, 1H), 7.64 (s, 1H), 7.48~7.35 (m, 5H), 7.15 (dd, J=4.9, 3.8 Hz, 1H), 4.86 (s, 1H), 4.31~4.11 (m, 4H), 1.22 (t, J=7.2 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 187.9, 167.5, 142.8, 141.9, 134.23, 134.17, 134.1, 133.9, 129.1, 128.81, 128.76, 127.8, 61.9, 51.7, 13.8; HRMS (ESI) calcd for C20H21O5S [M＋H]＋ 373.1104, found 373.1101.
(E)-2-(3-氧代-1-苯基丁-1-烯-2-基)丙二酸二乙酯(3aq): 柱层析[V(石油醚)∶V(乙酸乙酯)=4∶1]分离得无色油状液体, 产率12%. 1H NMR (CDCl3, 500 MHz) δ: 7.80 (s, 1H), 7.48~7.37 (m, 5H), 4.66 (s, 1H), 4.25~4.11 (m, 4H), 2.53 (s, 3H), 1.26 (t, J=7.1 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 197.9, 167.8, 143.3, 136.0, 134.3, 129.4, 128.81, 128.77, 61.7, 50.4, 25.7, 14.0; HRMS (ESI) calcd for C17H21O5 [M＋H]＋ 305.1384, found 305.1386.
(E)-2-(1-(4-氟苯基)-3-氧代-3-苯基丙-1-烯-2-基)丙二酸二乙酯(3ba): 柱层析[V(石油醚)∶V(乙酸乙酯)=12∶1]分离得黄色油状液体, 产率78%. 1H NMR (500 MHz, CDCl3) δ: 7.83 (d, J=7.3 Hz, 2H), 7.57 (t, J=7.4 Hz, 1H), 7.53~7.39 (m, 4H), 7.33 (s, 1H), 7.10 (t, J=8.6 Hz, 2H), 4.84 (s, 1H), 4.33~4.13 (m, 4H), 1.25 (t, J=7.1 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 196.6, 167.6, 163.1 (d, 1JFC=250.4 Hz), 142.9, 137.3, 134.4, 132.3, 130.8 (d, 3JFC=8.3 Hz), 130.2 (d, 4JFC=3.2 Hz), 129.9, 128.3, 115.9 (d, 2JFC=21.7 Hz), 62.0, 51.3, 14.0; 19F NMR (470 MHz, CDCl3) δ: －111.0; HRMS (ESI) calcd for C22H22FO5 [M＋H]＋ 385.1446, found 385.1451.
(E)-2-(1-(4-氯苯基)-3-氧代-3-苯基丙-1-烯-2-基)丙二酸二乙酯(3ca): 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得黄色固体, 产率83%. m.p. 64~65 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.90~7.77 (m, 2H), 7.57 (t, J=7.4 Hz, 1H), 7.53~7.44 (m, 2H), 7.43~7.34 (m, 4H), 7.31 (s, 1H), 4.82 (s, 1H), 4.34~4.12 (m, 4H), 1.25 (t, J=7.1 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 196.4, 167.5, 142.5, 137.2, 135.3, 134.9, 132.6, 132.4, 130.1, 129.9, 129.0, 128.3, 62.0, 51.4, 14.0; HRMS (ESI) calcd for C22H22ClO5 [M＋H]＋ 401.1150, found 401.1140.
(E)-2-(1-(4-溴苯基)-3-氧代-3-苯基丙-1-烯-2-基)丙二酸二乙酯(3da): 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得黄色油状液体, 产率81%. 1H NMR (500 MHz, CDCl3) δ: 7.83 (d, J=7.2 Hz, 2H), 7.62~7.52 (m, 3H), 7.51~7.44 (m, 2H), 7.35~7.27 (m, 3H), 4.81 (s, 1H), 4.32~4.13 (m, 4H), 1.25 (t, J=7.1 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 196.4, 167.5, 142.4, 137.2, 135.0, 133.1, 132.4, 132.0,130.3, 129.9, 128.3, 123.6, 62.0, 51.4, 13.9; HRMS (ESI) calcd for C22H22BrO5 [M＋H]＋ 445.0645, found 445.0650.
(E)-2-(3-氧代-3-苯基-1-(p-甲基苯基)丙-1-烯-2-基)丙二酸二乙酯(3ea): 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得黄色油状液体, 产率91%. 1H NMR (500 MHz, CDCl3) δ: 7.89~7.78 (m, 2H), 7.61~7.51 (m, 1H), 7.51~7.43 (m, 2H), 7.36 (s, 1H), 7.33~7.28 (m, 2H), 7.25~7.18 (m, 2H), 4.90 (s, 1H), 4.33~4.14 (m, 4H), 2.38 (s, 3H), 1.26 (t, J=7.2 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 196.8, 167.8, 144.5, 139.6, 137.7, 133.8, 132.1, 131.4, 129.8, 129.5, 128.9, 128.2, 61.8, 51.5, 21.4, 14.0; HRMS (ESI) calcd for C23H25O5 [M＋H]＋ 381.1697, found 381.1688.
(E)-2-(1-(2-甲氧基苯基)-3-氧代-3-苯基丙-1-烯-2-基)丙二酸二乙酯(3fa): 柱层析[V(石油醚)∶V(乙酸乙酯)=8∶1]分离得黄色油状液体, 产率88%. 1H NMR (500 MHz, CDCl3) δ: 7.91 (d, J=7.7 Hz, 2H), 7.62~7.52 (m, 1H), 7.52~7.33 (m, 5H), 6.99 (t, J=7.5 Hz, 1H), 6.91 (d, J=8.3 Hz, 1H), 4.75 (s, 1H), 4.33~4.11 (m, 4H), 3.81 (s, 3H), 1.25 (t, J=7.1 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 196.8, 168.0, 157.2, 140.9, 137.6, 134.0, 132.2, 130.8, 130.2, 129.6, 128.2, 123.4, 120.6, 110.6, 61.8, 55.5, 51.9, 14.0; HRMS (ESI) calcd for C23H25O6 [M＋H]＋ 397.1646, found 397.1650.
(E)-2-(1-(3-甲氧基苯基)-3-氧代-3-苯基丙-1-烯-2-基)丙二酸二乙酯(3ga): 柱层析[V(石油醚)∶V(乙酸乙酯)=10∶1]分离得黄色油状液体, 产率86%. 1H NMR (500 MHz, CDCl3) δ: 7.84 (d, J=7.4 Hz, 2H), 7.56 (t, J=7.4 Hz, 1H), 7.52~7.43 (m, 2H), 7.36 (s, 1H), 7.32 (t, J=7.9 Hz, 1H), 7.01~6.88 (m, 3H), 4.91 (s, 1H), 4.32~4.14 (m, 4H), 3.81 (s, 3H), 1.25 (t, J=7.1 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 196.6, 167.7, 159.7, 144.0, 137.5, 135.5, 134.5, 132.2, 129.9, 129.8, 128.3, 121.1, 115.2, 113.8, 61.9, 55.3, 51.6, 13.9; HRMS (ESI) calcd for C23H25O6 [M＋H]＋ 397.1646, found 397.1654.
(E)-2-(1-(4-甲氧基苯基)-3-氧代-3-苯基丙-1-烯-2-基)丙二酸二乙酯(3ha): 柱层析[V(石油醚)∶V(乙酸乙酯)=8∶1]分离得黄色固体, 产率92%. m.p. 53~54 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.86~7.76 (m, 2H), 7.55 (t, J=7.4 Hz, 1H), 7.51~7.43 (m, 2H), 7.42~7.32 (m, 3H), 6.93 (d, J=8.7 Hz, 2H), 4.92 (s, 1H), 4.37~4.11 (m, 4H), 3.84 (s, 3H), 1.26 (t, J=7.1 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 196.9, 167.9, 160.5, 144.5, 137.9, 132.8, 132.0, 130.8, 129.8, 128.2, 126.6, 114.3, 61.9, 55.4, 51.4, 14.0; HRMS (ESI) calcd for C23H25O6 [M＋H]＋ 397.1646, found 397.1647.
(E)-2-(3-氧代-3-苯基-1-(4-(三氟甲基)苯基)丙-1-烯-2-基)丙二酸二乙酯(3ia): 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得黄色油状液体, 产率80%. 1H NMR (500 MHz, CDCl3) δ: 7.93~7.81 (m, 2H), 7.68 (d, J=8.2 Hz, 2H), 7.63~7.44 (m, 5H), 7.36 (s, 1H), 4.78 (s, 1H), 4.33~4.12 (m, 4H), 1.25 (t, J=7.1 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 196.2, 167.4, 141.7, 137.9, 137.0, 136.1, 132.6, 131.0 (q, 2JFC=32.5 Hz), 130.0, 129.0, 128.4, 125.7 (q, 3JFC=3.5 Hz), 123.8 (q, 1JFC=272.7 Hz), 62.1, 51.5, 14.0; 19F NMR (470 MHz, CDCl3) δ: －62.8; HRMS (ESI) calcd for C23H22F3O5 [M＋H]＋ 435.1414, found 435.1422.
(E)-2-(1-(3-硝基苯基)-3-氧代-3-苯基丙-1-烯-2-基)丙二酸二乙酯(3ka): 柱层析[V(石油醚)∶V(乙酸乙 酯)=8∶1]分离得黄色油状液体, 产率78%. 1H NMR (500 MHz, CDCl3) δ: 8.33 (s, 1H), 8.25 (d, J=8.2 Hz, 1H), 7.93~7.86 (m, 2H), 7.82 (d, J=7.6 Hz, 1H), 7.68~7.58 (m, 2H), 7.56~7.48 (m, 2H), 7.35 (s, 1H), 4.75 (s, 1H), 4.34~4.17 (m, 4H), 1.27 (t, J=7.1 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 196.0, 167.2, 148.4, 140.1, 136.74, 136.71, 135.9, 134.6, 132.8, 129.99, 129.96, 128.5, 123.8, 123.7, 62.3, 51.5, 13.9; HRMS (ESI) calcd for C22H22NO7 [M＋H]＋ 412.1391, found 412.1393.
(E)-2-(1-(呋喃-2-基)-3-氧代-3-苯基丙-1-烯-2-基)丙二酸二乙酯(3ma): 柱层析[V(石油醚)∶V(乙酸乙酯)=10∶1]分离得黄色油状液体, 产率88%. 1H NMR (500 MHz, CDCl3) δ: 7.80~7.67 (m, 2H), 7.62~7.50 (m, 2H), 7.50~7.40 (m, 2H), 7.01 (s, 1H), 6.63 (d, J=3.4 Hz, 1H), 6.54~6.45 (m, 1H), 5.40 (s, 1H), 4.31~4.15 (m, 4H), 1.24 (t, J=7.1 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ: 196.5, 167.8, 149.9, 145.6, 137.9, 131.8, 130.7, 129.8, 129.5, 128.3, 117.8, 112.5, 61.7, 51.8, 14.0; HRMS (ESI) calcd for C20H21O6 [M＋H]＋ 357.1333, found 357.1335.
3.2.2 环丙烷衍生物4的合成
在经无水无氧处理过的反应管中加0.6 mmol三甲基碘化亚砜, 4 mL无水DMF, 0.9 mmol 60%氢化钠和0.3 mmol化合物3, 搅拌10 min后将反应管移入50 ℃的金属浴中搅拌反应, TLC跟踪至化合物3消失, 冷却至室温, 并加入5 mL饱和氯化铵水溶液淬灭反应, 用乙酸乙酯萃取(5 mL×3), 合并有机相, 用饱和氯化钠水溶液洗涤(5 mL×3), 无水硫酸钠干燥, 过滤, 回收乙酸乙酯, 柱层析分离得纯的产物4.
2-(R-1-苯甲酰基-trans-2-苯基环丙基)丙二酸二乙酯(4a): 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得无色固体, 产率88%. m.p. 50~51 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.70~7.58 (m, 2H), 7.50~7.38 (m, 3H), 7.35~7.27 (m, 3H), 7.26~7.22 (m, 2H), 4.20~4.07 (m, 2H), 4.06~3.91 (m, 2H), 3.18~3.07 (m, 1H), 2.80 (s, 1H), 1.93 (dd, J=7.3, 6.4 Hz, 1H), 1.67 (dd, J=9.3, 6.2 Hz, 1H), 1.22 (t, J=7.1 Hz, 3H), 1.08 (t, J=7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 202.9, 169.0, 168.2, 137.8, 135.1, 130.6, 129.2, 128.4, 128.1, 127.5, 127.4, 61.6, 61.2, 53.2, 37.9, 28.5, 17.1, 13.9; HRMS (ESI) calcd for C23H24- O5Na [M＋Na]＋ 403.1516, found 403.1506.
2-(R-1-苯甲酰基-trans-2-苯基环丙基)丙二酸二甲酯(4b): 柱层析[V(石油醚)∶V(乙酸乙酯)=12∶1]分离得黄色油状液体, 产率80%. 1H NMR (500 MHz, CDCl3) δ: 7.68~7.60 (m, 2H), 7.51~7.39 (m, 3H), 7.34~7.26 (m, 3H), 7.26~7.23 (m, 2H), 3.69 (s, 3H), 3.52 (s, 3H), 3.19~3.08 (m, 1H), 2.83 (s, 1H), 1.93 (dd, J=7.5, 6.3 Hz, 1H), 1.69 (dd, J=9.3, 6.3 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ: 202.9, 169.4, 168.7, 137.7, 134.9, 130.7, 129.2, 128.4, 128.2, 127.6, 127.5, 52.8, 52.6, 52.2, 38.0, 28.6, 16.5; HRMS (ESI) calcd for C21H21O5 [M＋H]＋ 353.1384, found 353.1380.
2-(R-1-苯甲酰基-trans-2-苯基环丙基)丙二酸二异丙酯(4c): 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得无色固体, 产率85%. m.p. 85~86 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.72~7.59 (m, 2H), 7.49~7.35 (m, 3H), 7.33~7.26 (m, 2H), 7.26~7.19 (m, 3H), 5.07~4.97 (m, 1H), 4.95~4.83 (m, 1H), 3.09 (dd, J=9.3, 7.5 Hz, 1H), 2.71 (s, 1H), 1.93 (dd, J=7.5, 6.2 Hz, 1H), 1.61 (dd, J=9.3, 6.2 Hz, 1H), 1.213 (d, J=6.3 Hz, 3H), 1.210 (d, J=6.3 Hz, 3H), 1.12 (d, J=6.3 Hz, 3H), 0.99 (d, J=6.3 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 202.6, 168.3, 167.6, 137.7, 135.1, 130.4, 129.0, 128.3, 127.9, 127.4, 127.2, 69.0, 68.4, 53.4, 37.8, 28.1, 21.5, 21.4, 21.33, 21.27, 16.1; HRMS (ESI) calcd for C25H29O5 [M＋H]＋ 409.2010, found 409.2013.
2-(R-1-(4-氟苯甲酰基)-trans-2-苯基环丙基)丙二酸二乙酯(4d): 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得黄色固体, 产率86%. m.p. 81~82 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.78~7.66 (m, 2H), 7.35~7.26 (m, 3H), 7.26~7.22 (m, 2H), 7.16~7.06 (m, 2H), 4.20~4.06 (m, 2H), 4.05~3.91 (m, 2H), 3.16~3.06 (m, 1H), 2.81 (s, 1H), 1.96 (dd, J=7.4, 6.3 Hz, 1H), 1.62 (dd, J=9.3, 6.2 Hz, 1H), 1.22 (t, J=7.2 Hz, 3H), 1.08 (t, J=7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 201.4, 168.9, 168.3, 164.2 (d, 1JFC=251.6 Hz), 135.1, 133.9 (d, 4JFC=3.1 Hz), 130.3 (d, 3JFC=8.7 Hz), 129.2, 128.5, 127.5, 115.2 (d, 2JFC=21.8 Hz), 61.6, 61.2, 53.3, 37.6, 28.3, 16.4, 13.9; 19F NMR (470 MHz, CDCl3) δ: －108.4; HRMS (ESI) calcd for C23H24FO5 [M＋H]＋ 399.1602, found 399.1600.
2-(R-1-(4-氯苯甲酰基)-trans-2-苯基环丙基)丙二酸二乙酯(4e): 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得黄色油状液体, 产率88%. 1H NMR (500 MHz, CDCl3) δ: 7.66~7.57 (m, 2H), 7.44~7.35 (m, 2H), 7.34~7.20 (m, 5H), 4.18~4.06 (m, 2H), 4.04~3.91 (m, 2H), 3.08 (dd, J=9.3, 7.5 Hz, 1H), 2.80 (s, 1H), 1.95 (dd, J=7.5, 6.3 Hz, 1H), 1.62 (dd, J=9.3, 6.3 Hz, 1H), 1.21 (t, J=7.2 Hz, 3H), 1.06 (t, J=7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 201.6, 168.7, 168.1, 136.8, 136.1, 134.8, 129.1, 129.0, 128.4, 128.3, 127.4, 61.5, 61.1, 53.1, 37.6, 28.3, 16.4, 13.8; HRMS (ESI) calcd for C23H24ClO5 [M＋H]＋ 415.1307, found 415.1304.
2-(R-1-(4-溴苯甲酰基)-trans-2-苯基环丙基)丙二酸二乙酯(4f): 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得黄色固体, 产率81%. m.p. 119~120 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.62~7.49 (m, 4H), 7.35~7.19 (m, 5H), 4.19~4.05 (m, 2H), 4.05~3.90 (m, 2H), 3.14~3.03 (m, 1H), 2.79 (s, 1H), 1.95 (dd, J=7.4, 6.3 Hz, 1H), 1.62 (dd, J=9.3, 6.2 Hz, 1H), 1.21 (t, J=7.2 Hz, 3H), 1.07 (t, J=7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 201.8, 168.8, 168.2, 136.6, 134.8, 131.3, 129.3, 129.1, 128.4, 127.5, 125.2, 61.6, 61.2, 53.1, 37.7, 28.4, 16.5, 13.8; HRMS (ESI) calcd for C23H23BrO5Na [M＋Na]＋ 481.0621, found 481.0625.
2-(R-1-(4-甲基苯甲酰基)-trans-2-苯基环丙基)丙二酸二乙酯(4g): 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得黄色油状液体, 产率85%. 1H NMR (500 MHz, CDCl3) δ: 7.58 (d, J=8.1 Hz, 2H), 7.34~7.18 (m, 7H), 4.20~4.08 (m, 2H), 4.05~3.92 (m, 2H), 3.18~3.07 (m, 1H), 2.82 (s, 1H), 2.37 (s, 3H), 1.92 (dd, J=7.3, 6.3 Hz, 1H), 1.64 (dd, J=9.3, 6.2 Hz, 1H), 1.22 (t, J=7.2 Hz, 3H), 1.08 (t, J=7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 202.4, 168.9, 168.1, 141.0, 135.2, 134.8, 129.1, 128.7, 128.3, 127.8, 127.3, 61.4, 61.0, 53.2, 37.7, 28.4, 21.4, 16.3, 13.8; HRMS (ESI) calcd for C24H27O5 [M＋H]＋ 395.1853, found 395.1853.
2-(R-1-(2-甲氧基苯甲酰基)-trans-2-苯基环丙基)丙二酸二乙酯(4h): 柱层析[V(石油醚)∶V(乙酸乙酯)=8∶1]分离得黄色固体, 产率92%. m.p. 61~62 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.42~7.14 (m, 7H), 6.99 (t, J=7.4 Hz, 1H), 6.92 (d, J=8.2 Hz, 1H), 4.25~4.08 (m, 2H), 4.05~3.92 (m, 2H), 3.86 (s, 3H), 3.04~2.94 (m, 1H), 2.81 (s, 1H), 1.85~1.73 (m, 2H), 1.25 (t, J=7.1 Hz, 3H), 1.11 (t, J=7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 202.6, 168.6, 167.7, 155.6, 134.9, 130.4, 129.2, 128.1, 128.0, 127.23, 127.20, 120.2, 111.2, 61.2, 60.8, 55.6, 52.1, 39.8, 30.4, 17.6, 13.9, 13.8; HRMS (ESI) calcd for C24H27O6 [M＋H]＋ 411.1802, found 411.1793.
2-(R-1-(3-甲氧基苯甲酰基)-trans-2-苯基环丙基)丙二酸二乙酯(4i): 柱层析[V(石油醚)∶V(乙酸乙酯)=10∶1]分离得黄色油状液体, 产率87%. 1H NMR (500 MHz, CDCl3) δ: 7.38~7.20 (m, 7H), 7.15 (dd, J=2.5, 1.4 Hz, 1H), 7.04~6.94 (m, 1H), 4.21~4.08 (m, 2H), 4.06~3.92 (m, 2H), 3.84 (s, 3H), 3.21~3.10 (m, 1H), 2.81 (s, 1H), 1.93 (dd, J=7.5, 6.3 Hz, 1H), 1.70 (dd, J=9.3, 6.2 Hz, 1H), 1.23 (t, J=7.1 Hz, 3H), 1.09 (t, J=7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 202.6, 168.9, 168.1, 159.3, 139.0, 135.1, 129.2, 128.4, 127.4, 119.7, 116.5, 112.7, 61.5, 61.1, 55.4, 53.1, 38.0, 28.7, 16.7, 13.89, 13.87; HRMS (ESI) calcd for C24H27O6 [M＋H]＋ 411.1802, found 411.1796.
2-(R-1-(4-甲氧基苯甲酰基)-trans-2-苯基环丙基)丙二酸二乙酯(4j): 柱层析[V(石油醚)∶V(乙酸乙酯)=8∶1]分离得黄色固体, 产率85%. m.p. 71~72 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.75 (d, J=8.4 Hz, 2H), 7.38~7.18 (m, 5H), 6.92 (d, J=8.6 Hz, 2H), 4.20~4.08 (m, 2H), 4.05~3.92 (m, 2H), 3.83 (s, 3H), 3.20~3.08 (m, 1H), 2.83 (s, 1H), 2.00~1.89 (m, 1H), 1.60 (dd, J=9.2, 6.2 Hz, 1H), 1.21 (t, J=7.1 Hz, 3H), 1.06 (t, J=7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 201.0, 169.0, 168.3, 161.9, 135.4, 130.3, 129.9, 129.1, 128.4, 127.3, 113.3, 61.5, 61.1, 55.3, 53.6, 37.2, 28.2, 16.1, 13.84, 13.83; HRMS (ESI) calcd for C24H27O6 [M＋H]＋ 411.1802, found 411.1800.
2-(R-1-(3,4-二甲氧基苯甲酰基)-trans-2-苯基环丙基)丙二酸二乙酯(4k): 柱层析[V(石油醚)∶V(乙酸乙 酯)=2∶1]分离得黄色油状液体, 产率84%. 1H NMR (500 MHz, CDCl3) δ: 7.46 (dd, J=8.3, 1.9 Hz, 1H), 7.35~7.20 (m, 6H), 6.88 (d, J=8.3 Hz, 1H), 4.18~4.05 (m, 2H), 4.03~3.93 (m, 2H), 3.92 (s, 3H), 3.91 (s, 3H), 3.23~3.13 (m, 1H), 2.83 (s, 1H), 1.94 (dd, J=7.3, 6.3 Hz, 1H), 1.63 (dd, J=9.3, 6.2 Hz, 1H), 1.20 (t, J=7.2 Hz, 3H), 1.06 (t, J=7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 200.7, 169.0, 168.2, 151.6, 148.6, 135.4, 129.9, 129.1, 128.4, 127.3, 122.1, 111.5, 109.8, 61.5, 61.1, 56.0, 53.6, 37.1, 28.3, 16.3, 13.85, 13.83; HRMS (ESI) calcd for C25H29O7 [M＋H]＋ 441.1908, found 441.1902.
2-(trans-2-苯基-R-1-(4-(三氟甲基)苯甲酰基)环丙基)丙二酸二乙酯(4l): 柱层析[V(石油醚)∶V(乙酸乙 酯)=10∶1]分离得黄色固体, 产率66%. m.p. 99~100 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.74 (d, J=8.1 Hz, 2H), 7.68 (d, J=8.2 Hz, 2H), 7.35~7.21 (m, 5H), 4.18~4.04 (m, 2H), 4.04~3.91 (m, 2H), 3.13~3.04 (m, 1H), 2.80 (s, 1H), 1.98 (dd, J=7.5, 6.4 Hz, 1H), 1.67 (dd, J=9.4, 6.3 Hz, 1H), 1.20 (t, J=7.2 Hz, 3H), 1.07 (t, J=7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 202.0, 168.8, 168.2, 141.5, 134.7, 132.2 (q, 2JFC=32.7 Hz), 129.2, 128.5, 127.8, 127.6, 125.2 (q, 3JFC=3.6 Hz), 123.7 (q, 1JFC=272.5 Hz), 61.7, 61.3, 53.0, 38.0, 28.6, 16.8, 13.8; 19F NMR (470 MHz, CDCl3) δ: －63.0; HRMS (ESI) calcd for C24H24F3O5 [M＋H]＋ 449.1570, found 449.1561.
2-(trans-2-苯基-R-1-(噻吩-2-甲酰基)环丙基)丙二酸二乙酯(4o): 柱层析[V(石油醚)∶V(乙酸乙酯)=5∶1]分离得黄色油状液体, 产率80%. 1H NMR (500 MHz, CDCl3) δ: 7.67 (d, J=3.6 Hz, 1H), 7.60 (d, J=4.8 Hz, 1H), 7.36~7.27 (m, 5H), 7.16~7.08 (m, 1H), 4.24~4.11 (m, 2H), 4.05~3.88 (m, 2H), 3.61~3.48 (m, 1H), 2.78 (s, 1H), 2.21~2.08 (m, 1H), 2.03~1.90 (m, 1H), 1.24 (t, J=7.1 Hz, 3H), 1.07 (t, J=7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 191.4, 168.7, 167.6, 141.2, 134.9, 132.6, 131.3, 129.3, 128.4, 127.7, 127.5, 61.5, 61.0, 53.7, 39.0, 31.4, 19.0, 13.9, 13.8; HRMS (ESI) calcd for C21H23O5S [M＋H]＋ 387.1261, found 387.1253.
2-(R-1-苯甲酰基-trans-2-(4-氟苯基)环丙基)丙二酸二乙酯(4p): 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得白色固体, 产率83%. m.p. 88~89 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.66~7.58 (m, 2H), 7.52~7.36 (m, 3H), 7.26~7.18 (m, 2H), 7.04~6.97 (m, 2H), 4.19~4.08 (m, 2H), 4.08~3.93 (m, 2H), 3.13~3.01 (m, 1H), 2.78 (s, 1H), 1.88 (dd, J=7.3, 6.4 Hz, 1H), 1.69 (dd, J=9.3, 6.3 Hz, 1H), 1.22 (t, J=7.2 Hz, 3H), 1.11 (t, J=7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 202.6, 168.8, 168.1, 162.1 (d, 1JFC=246.6 Hz), 137.8, 130.9 (d, 4JCF=3.2 Hz), 130.8 (d, 3JCF=8.1 Hz), 130.6, 128.1, 127.5, 115.3 (d, 2JCF=21.6 Hz), 61.6, 61.3, 53.1, 37.8, 27.7, 16.7, 13.9; 19F NMR (470 MHz, CDCl3) δ: －114.7; HRMS (ESI) calcd for C23H24FO5 [M＋H]＋ 399.1602, found 399.1592.
2-(R-1-苯甲酰基-trans-2-(4-氯苯基)环丙基)丙二酸二乙酯(4q): 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得黄色固体, 产率81%. m.p. 109~110 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.61 (d, J=7.9 Hz, 2H), 7.51~7.35 (m, 3H), 7.27 (d, J=8.2 Hz, 2H), 7.19 (d, J=8.3 Hz, 2H), 4.19~4.07 (m, 2H), 4.06~3.92 (m, 2H), 3.13~2.97 (m, 1H), 2.78 (s, 1H), 1.95~1.82 (m, 1H), 1.75~1.63 (m, 1H), 1.20 (t, J=7.1 Hz, 3H), 1.10 (t, J=7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 202.4, 168.6, 168.0, 137.6, 133.7, 133.3, 130.63, 130.55, 128.5, 128.1, 127.4, 61.6, 61.3, 53.0, 37.8, 27.8, 16.5, 13.8; HRMS (ESI) calcd for C23H24ClO5 [M＋H]＋ 415.1307, found 415.1313.
2-(R-1-苯甲酰基-trans-2-(4-溴苯基)环丙基)丙二酸二乙酯(4r): 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得白色固体, 产率80%. m.p. 118~119 oC; 1H NMR (500 MHz, CDCl3) δ: 7.72~7.55 (m, 2H), 7.53~7.36 (m, 5H), 7.13 (d, J=8.4 Hz, 2H), 4.21~4.06 (m, 2H), 4.06~3.92 (m, 2H), 3.12~2.95 (m, 1H), 2.79 (s, 1H), 1.96~1.82 (m, 1H), 1.69 (dd, J=9.2, 6.3 Hz, 1H), 1.21 (t, J=7.1 Hz, 3H), 1.10 (t, J=7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 202.4, 168.6, 168.0, 137.6, 134.3, 131.5, 130.9, 130.7, 128.1, 127.4, 121.4, 61.6, 61.3, 53.0, 37.8, 27.9, 16.5, 13.9; HRMS (ESI) calcd for C23H24BrO5 [M＋H]＋ 459.0802, found 459.0808.
2-(R-1-苯甲酰基-trans-2-(p-甲基苯基)环丙基)丙二酸二乙酯(4s): 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得白色固体, 产率87%. m.p. 84~85 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.69~7.58 (m, 2H), 7.50~7.35 (m, 3H), 7.20~7.04 (m, 4H), 4.22~4.07 (m, 2H), 4.06~3.94 (m, 2H), 3.15~3.01 (m, 1H), 2.81 (s, 1H), 2.32 (s, 3H), 1.89 (dd, J=7.4, 6.2 Hz, 1H), 1.66 (dd, J=9.3, 6.2 Hz, 1H), 1.22 (t, J=7.2 Hz, 3H), 1.09 (t, J=7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 202.9, 169.0, 168.2, 137.9, 137.1, 132.0, 130.5, 129.1, 129.0, 128.1, 127.5, 61.5, 61.1, 53.1, 37.9, 28.3, 21.1, 16.5, 13.89, 13.86; HRMS (ESI) calcd for C24H27O5 [M＋H]＋ 395.1853, found 395.1844.
2-(R-1-苯甲酰基-trans-2-(2-甲氧基苯基)环丙基)丙二酸二乙酯(4t): 柱层析[V(石油醚)∶V(乙酸乙酯)=8∶1]分离得黄色固体, 产率87%. m.p. 61~62 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.86~7.77 (m, 2H), 7.50~7.37 (m, 3H), 7.30~7.23 (m, 1H), 7.07~7.01 (m, 1H), 6.95~6.84 (m, 2H), 4.17~3.92 (m, 4H), 3.91 (s, 3H), 3.12~3.05 (m, 1H), 3.03 (s, 1H), 1.96 (dd, J=7.7, 6.1 Hz, 1H), 1.64 (dd, J=9.4, 6.1 Hz, 1H), 1.21 (t, J=7.2 Hz, 3H), 1.06 (t, J=7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 203.2, 169.0, 167.8, 159.2, 137.7, 130.6, 129.0, 128.8, 128.0, 127.9, 123.9, 120.3, 109.9, 61.5, 61.0, 55.1, 52.7, 37.1, 25.5, 15.3, 13.9, 13.8; HRMS (ESI) calcd for C24H27O6 [M＋H]＋ 411.1802, found 411.1798.
2-(R-1-苯甲酰基-trans-2-(3-甲氧基苯基)环丙基)丙二酸二乙酯(4u): 柱层析[V(石油醚)∶V(乙酸乙酯)=10∶1]分离得黄色油状液体, 产率86%. 1H NMR (500 MHz, CDCl3) δ: 7.71~7.58 (m, 2H), 7.51~7.36 (m, 3H), 7.25~7.16 (m, 1H), 6.90~6.74 (m, 3H), 4.21~4.07 (m, 2H), 4.07~3.96 (m, 2H), 3.80 (s, 3H), 3.16~3.05 (m, 1H), 2.83 (s, 1H), 1.91 (dd, J=7.4, 6.3 Hz, 1H), 1.64 (dd, J=9.3, 6.2 Hz, 1H), 1.22 (t, J=7.1 Hz, 3H), 1.10 (t, J=7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 202.8, 169.0, 168.3, 159.6, 137.9, 136.8, 130.6, 129.5, 128.1, 127.6, 121.5, 115.3, 112.6, 61.6, 61.2, 55.2, 53.2, 37.8, 28.4, 16.7, 13.9; HRMS (ESI) calcd for C24H27O6 [M＋ H]＋ 411.1802, found 411.1796.
2-(R-1-苯甲酰基-trans-2-(4-甲氧基苯基)环丙基)丙二酸二乙酯(4v): 柱层析[V(石油醚)∶V(乙酸乙酯)=8∶1]分离得黄色固体, 产率90%. m.p. 71~72 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.68~7.58 (m, 2H), 7.51~7.32 (m, 3H), 7.16 (d, J=8.7 Hz, 2H), 6.82 (d, J=8.6 Hz, 2H), 4.21~4.08 (m, 2H), 4.07~3.95 (m, 2H), 3.76 (s, 3H), 3.10~2.98 (m, 1H), 2.80 (s, 1H), 1.92~1.78 (m, 1H), 1.65 (dd, J=9.3, 6.2 Hz, 1H), 1.21 (t, J=7.1 Hz, 3H), 1.10 (t, J=7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 202.9, 168.9, 168.2, 158.9, 137.8, 130.4, 130.2, 128.0, 127.3, 126.9, 113.7, 61.4, 61.1, 55.2, 53.0, 37.9, 28.0, 16.7, 13.8; HRMS (ESI) calcd for C24H27O6 [M＋ H]＋ 411.1802, found 411.1799.
2-(R-1-苯甲酰基-trans-2-(4-(三氟甲基)苯基)环丙基)丙二酸二乙酯(4w): 柱层析[V(石油醚)∶V(乙酸乙酯)=15∶1]分离得白色固体, 产率75%. m.p. 100~101 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.64 (d, J=7.2 Hz, 2H), 7.57 (d, J=8.1 Hz, 2H), 7.51~7.35 (m, 5H), 4.18~4.04 (m, 2H), 4.02~3.89 (m, 2H), 3.22~3.08 (m, 1H), 2.79 (s, 1H), 2.05~1.93 (m, 1H), 1.75 (dd, J=9.1, 6.4 Hz, 1H), 1.20 (t, J=7.1 Hz, 3H), 1.05 (t, J=7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 202.2, 168.5, 167.9, 139.5, 137.6, 130.8, 129.7 (q, 2JFC=32.8 Hz), 129.6, 128.2, 127.5, 125.3 (q, 3JFC=3.9 Hz), 124.0 (q, 1JFC=272.1 Hz), 61.7, 61.3, 53.1, 37.9, 28.0, 16.5, 13.83, 13.76; 19F NMR (470 MHz, CDCl3) δ: －62.6; HRMS (ESI) calcd for C24H24F3O5 [M＋H]＋ 449.1570, found 449.1567.
2-(R-1-苯甲酰基-trans-2-(呋喃-2-基)环丙基)丙二酸二乙酯(4y): 柱层析[V(石油醚)∶V(乙酸乙酯)=10∶1]分离得黄色油状液体, 产率75%. 1H NMR (500 MHz, CDCl3) δ: 7.70~7.59 (m, 2H), 7.49~7.37 (m, 3H), 7.37~7.30 (m, 1H), 6.35~6.28 (m, 1H), 6.21~6.13 (m, 1H), 4.21~4.11 (m, 2H), 4.10~3.99 (m, 2H), 3.15 (s, 1H), 2.89 (dd, J=9.5, 7.2 Hz, 1H), 1.86~1.73 (m, 2H), 1.23 (t, J=7.2 Hz, 3H), 1.13 (t, J=7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 201.6, 168.6, 168.0, 150.6, 142.3, 137.4, 130.9, 128.1, 127.8, 110.6, 108.8, 61.6, 61.3, 53.3, 37.5, 21.8, 17.0, 13.9; HRMS (ESI) calcd for C21H22O6Na [M＋Na]＋ 393.1309, found 393.1304.
3.2.3 环丙烷衍生物4与乌洛托品或三嗪烷的环化反应
在经无水无氧处理过的反应管中加0.2 mmol环丙烷4a, 0.2 mmol乌洛托品或1,3,5-三苯基-1,3,5-三嗪烷, 2 mL无水甲苯, 搅拌10 min后将反应管移入120或110 ℃的金属浴中搅拌反应, TLC跟踪至化合物4a消失, 冷却至室温并加入2 mL饱和氯化铵水溶液淬灭反应, 用二氯甲烷萃取(5 mL×3), 合并有机相, 无水硫酸钠干燥, 过滤, 回收溶剂, 柱层析分离得纯的产物5a或6a和7a. 环丙烷4d与1,3,5-三苯基-1,3,5-三嗪烷的反应得产物7d.
3-氧代-1,6-二苯基-4,5,6,7-四氢呋喃并[3,4-c]吡啶- 3a(3H)-羧酸乙酯(5a): 柱层析[V(石油醚)∶V(乙酸乙 酯)=2∶1]分离得无色油状液体, 产率50%. 1H NMR (500 MHz, CDCl3) δ: 7.64~7.56 (m, 2H), 7.49~7.38 (m, 3H), 7.37~7.28 (m, 5H), 4.45~4.34 (m, 3H), 3.92~3.83 (m, 2H), 3.00 (d, J=12.1 Hz, 1H), 2.48 (dd, J=12.9, 11.2 Hz, 1H), 1.89 (s, 1H), 1.39 (t, J=7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 179.7, 167.8, 161.4, 141.3, 135.6, 129.3, 129.1, 128.8, 128.3, 127.0, 126.6, 116.8, 84.0, 63.6, 61.6, 56.9, 37.4, 14.2; HRMS (ESI) calcd for C22H22NO4 [M＋H]＋ 364.1543, found 364.1549.
(5-endo)-2-氧代-5,11-二苯基-4,5-二氢-2H-4,9b-(亚甲基氨基亚甲基)萘并[1,2-b]呋喃-3-羧酸乙酯(6a): 柱层析[V(石油醚)∶V(乙酸乙酯)=10∶1]分离得无色固体, 产率28%. m.p. 150~151 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.66 (dd, J=7.9, 1.1 Hz, 1H), 7.35~7.29 (m, 1H), 7.25~7.12 (m, 6H), 6.94~6.79 (m, 4H), 6.70~6.62 (m, 2H), 4.63 (s, 1H), 4.28~4.18 (m, 1H), 4.16~4.00 (m, 4H), 3.32~3.25 (m, 1H), 3.00 (d, J=10.8 Hz, 1H), 0.98 (t, J=7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 177.7, 167.4, 160.4, 149.2, 145.2, 138.8, 135.7, 129.2, 128.9, 128.7, 128.6, 127.65, 127.61, 127.0, 124.3, 120.9, 117.3, 114.1, 81.4, 63.3, 61.0, 57.2, 55.5, 44.9, 13.8; HRMS (ESI) calcd for C29H26NO4 [M＋H]＋452.1856, found 452.1865.
(5-exo)-2-氧代-5,11-二苯基-4,5-二氢-2H-4,9b-(亚甲基氨基亚甲基)萘并[1,2-b]呋喃-3-羧酸乙酯(7a): 柱层析[V(石油醚)∶V(乙酸乙酯)=10∶1]分离得无色油状液体, 产率20%. 1H NMR (500 MHz, CDCl3) δ: 7.66 (dd, J=7.8, 1.4 Hz, 1H), 7.52~7.29 (m, 4H), 7.24~7.07 (m, 4H), 7.05~6.90 (m, 2H), 6.84 (t, J=7.4 Hz, 1H), 6.55 (d, J=7.7 Hz, 2H), 4.82 (d, J=6.1 Hz, 1H), 4.41 (q, J=7.1 Hz, 2H), 4.28~4.17 (m, 2H), 3.55 (d, J=12.3 Hz, 1H), 2.99 (d, J=10.6 Hz, 1H), 2.86~2.76 (m, 1H), 1.42 (t, J=7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 180.4, 167.1, 161.1, 148.8, 140.7, 138.6, 136.4, 130.1, 129.1, 128.8, 128.64, 128.55, 128.3, 127.7, 124.6, 120.7, 116.9, 112.9, 81.3, 63.4, 61.5, 52.0, 51.6, 42.0, 14.3; HRMS (ESI) calcd for C29H26NO4 [M＋H]＋ 452.1856, found 452.1862.
(5-exo)-5-(4-氟苯基)-2-氧代-11-苯基-4,5-二氢-2H- 4,9b-(亚甲基氨基亚甲基)萘并[1,2-b]呋喃-3-羧酸乙酯(7d): 柱层析[V(石油醚)∶V(乙酸乙酯)=10∶1]分离得黄色固体, 产率30%. m.p. 150~151 ℃; 1H NMR (500 MHz, CDCl3) δ: 7.66 (dd, J=7.9, 1.2 Hz, 1H), 7.37~7.29 (m, 1H), 7.23~7.10 (m, 3H), 6.99~6.88 (m, 2H), 6.88~6.78 (m, 4H), 6.72~6.59 (m, 2H), 4.62 (s, 1H), 4.26~4.18 (m, 1H), 4.17~4.02 (m, 4H), 3.32~3.21 (m, 1H), 3.00 (d, J=10.9 Hz, 1H), 1.05 (t, J=7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ: 177.5, 167.3, 161.8 (d, 1JFC=246.3 Hz), 160.4, 149.2, 141.1, 138.7, 135.7, 129.23, 129.18 (d, 3JFC=8.3 Hz), 129.0, 128.6, 127.8, 124.5, 121.0, 117.3, 115.5 (d, 2JFC=21.4 Hz), 114.3, 81.4, 63.4, 61.2, 57.2, 54.7, 44.9, 13.8; 19F NMR (470 MHz, CDCl3) δ: －115.6; HRMS (ESI) calcd for C29H25FNO4 [M＋H]＋ 470.1762, found 470.1758.
辅助材料(Supporting Information) 化合物3aa、3'aa、3ab~3al、3an~3aq、3ba~3ia、3ka、3ma、4a~4l、4o~4w、4y、5a、6a、7a和7d的1H NMR和13C NMR图谱以及含氟化合物3ad、3al、3ba、3ia、4d、4l、4p、4w和7d的19F NMR图谱. 这些材料可以免费从本刊网站(http://sioc-journal.cn/)上下载.
(Zhao, C.)