CN115197199A - 一种含有双取代吲哚酮骨架的芳胺化合物及其合成方法 - Google Patents
一种含有双取代吲哚酮骨架的芳胺化合物及其合成方法 Download PDFInfo
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Abstract
本发明公开了一种含有双取代吲哚酮骨架的芳胺化合物的合成方法,包括以下步骤:以3‑吡咯基羟吲哚和乙烯基苯并恶嗪酮为反应物,在手性草酰胺膦配体、三(二亚苄基丙酮)二钯‑氯仿加合物存在下,在有机溶剂中,反应得到含有双取代吲哚酮骨架的芳胺化合物。本发明方法操作简便,收率良好,化学选择性择性好;反应后处理简单,体系中没有副产物生成;适用底物范围广,原料均为工业化、廉价易得的产品,无污染;并且官能团兼容性高,对映选择性优秀。
Description
技术领域
本发明属于有机合成技术,具体涉及一种含有双取代吲哚酮骨架的芳胺化合物的合成方法。
背景技术
含氮杂环化合物是最大的有机化合物家族之一,广泛存在于各种生物活性天然生物碱和生物活性化合物中。因此,此类框架的构建已成为有机合成中的一个重要问题。在众多方法中,乙烯基苯并恶嗪酮最近被认为是一类用于构建结构多样且复杂的含氮手性骨架的强大且通用的构建块。同时利用3-吡咯基羟吲哚作为亲核试剂与乙烯基苯并恶嗪酮发生线性选择性的烯丙基取代反应来构建广泛存在于药物候选分子中十分重要的的含有双取代吲哚酮骨架的手性芳胺骨架。
现有技术中关于乙烯基苯并恶嗪酮的各种环加成反应的合成方法比较常见但用乙烯基苯并恶嗪酮作为一个有效的烯丙基化试剂来发生线性选择性的烯丙基烷基化反应的合成方法鲜有报道。2019年,江苏师范大学石枫课题组报道了铱/布朗斯特酸协同催化的N-Ts保护的乙烯基苯并恶嗪酮和吖内酯之间的线性选择性烯丙基烷基化反应(M. Sun, X.Wan, S. J. Zhou, G. J. Mei, F. Shi, Chem. Commun. 2019, 55, 1283–1286)。2021年,李灿课题组报道了钯/手性亚膦酰胺催化的乙烯基苯并恶嗪酮与α-硫氰酸酮的不对称烯丙基烷基化(AAA),得到具有高线性、E和立体选择性的各种手性硫氰酸酯(K. Wang, B.Wang, X. Liu, H. Fan, Y. Liu, C. Li, Chin. J. Catal. 2021, 42, 1227–1237)。这是文献报道的关于乙烯基苯并恶嗪酮发生线性选择性烯丙基烷基化反应的实验方法。不过现有方法采用的反应条件还需简化,产物的手性值还需提高。
发明内容
本发明的目的是提供含有双取代吲哚酮骨架的芳胺化合物及其合成方法,具体为含一个季碳手性中心的吲哚酮类芳胺化合物及其催化合成方法,该化合物分子结构中还有重要的吲哚酮结构及芳胺单元,为常规功能片段。
为达到上述发明目的,本发明采用的技术方案是:
一种含有双取代吲哚酮骨架的手性芳胺化合物的合成方法,包括以下步骤:以3-吡咯基羟吲哚和乙烯基苯并恶嗪酮为反应物,在手性草酰胺膦配体、三(二亚苄基丙酮)二钯-氯仿加合物存在下,在有机溶剂中,反应得到手性吲哚酮类芳胺化合物;
所述乙烯基苯并恶嗪酮的化学结构式为:
所述3-吡咯基羟吲哚的化学结构式为:
所述手性哚酮类芳胺化合物的化学结构式为:
上述结构式中,R1选自:氢、3-甲基、4-氟、4-氯、4-溴、4-三氟甲基、5-氯、5-溴、5-甲基、6-氯、6-甲基; R2选自:氢、4-氯、4-溴、5-氟、5-氯、5-溴5-甲基、5-甲氧基、5-硝基、6-氟、6-氯、6-溴、6-甲氧基、6-溴、5 ,7-二甲基或者7-三氟甲基、7-甲基、7-氟。
上述技术方案中,有机溶剂独立地选自醚类、卤代烃类、 苯类溶剂或者质子性溶剂;优选的技术方案中,反应体系中使用四氢呋喃为溶剂和手性草酰胺膦配体为催化剂,以提高反应收率以及立体选择性。
上述技术方案中,以摩尔量计,所述手性草酰胺膦配体的用量为3-吡咯基羟吲哚的5~12%,优选的,所述手性草酰胺膦配体的用量为3-吡咯基羟吲哚的6%;所述手性草酰胺膦配体化合物的化学结构式如下所示:
上述技术方案中,以摩尔量计,所述乙烯基苯并恶嗪酮用量为3-吡咯基羟吲哚的0.6~1.5倍;所述三(二亚苄基丙酮)二钯-氯仿加合物的用量为3-吡咯基羟吲哚的2.5~5%;优选的,所述乙烯基苯并恶嗪酮用量为3-吡咯基羟吲哚的1 .5倍,三(二亚苄基丙酮)二钯-氯仿加合物的用量为3-吡咯基羟吲哚的2.5%。
上述技术方案中,所述反应的时间为24~48小时;所述反应的温度为室温;所述反应结束后,经过梯度柱层析得到产物。
本发明以3-吡咯基羟吲哚和乙烯基苯并恶嗪酮为反应物,通过不对称线性选择性的烯丙基烷基化反应得到手性吲哚酮类芳胺化合物;反应过程包括在室温下,向反应瓶中加入手性草酰胺膦配体、三(二亚苄基丙酮)二钯-氯仿加合物、3-吡咯基羟吲哚、乙烯基苯并恶嗪酮、溶剂,磁力搅拌进行反应,反应结束后,减压除去溶剂,粗产物通过简单的柱层析(洗脱剂优选为石油醚∶乙酸乙酯=5∶1~3∶1)分离,该类化合物具有吲哚酮和手性芳胺的结构,为常规的具有药理活性的化合物结构单元,因而具有巨大的潜在应用价值;而且本发明产物带有双键、胺基、酮基、卤素等,胺基为活性基团,可与羧基、环氧基等进行反应,结合本发明可规模化合成,本发明化合物可在材料领域具有应用,比如参与环氧体系的固化提供阻燃、耐热等效果,图1为3fa(35mg)溶解在5ml三氯甲烷形成的黄色溶液。
由于上述技术方案运用,本发明与现有技术相比具有下列优点:
1.本发明实现了以以3-吡咯基羟吲哚和乙烯基苯并恶嗪酮为反应物,手性草酰胺膦配体、在三(二亚苄基丙酮)二钯-氯仿加合物存在下下,合成一种手性吲哚酮类芳胺化合物的方法,该方法操作简便,收率良好,化学选择性择性好;
2.本发明所公开的合成手性哚酮类芳胺化合物的反应后处理简单,体系中没有副产物生成;
3.本发明公开的合成一种化合物手性吲哚酮类芳胺化合物的方法适用底物范围广,原料均为工业化、廉价易得的产品,无污染;并且官能团兼容性高,对映选择性优秀。
附图说明
图1为产物3fa的三氯甲烷溶液。
具体实施方式
本发明采用的原料为现有物质,或者根据现有常规方法可得到,具体制备操作以及测试方法为常规技术。下面结合实施例对本发明作进一步描述。
以下例子涉及的L如下:
合成例
表1 不同膦配体化合物的反应结果
反应条件: 1a (0.1 mmol), 2a (0.1 mmol), Pd2(dba)3·CHCl3 (5 mol%) ,L(12 mol%),2 mL DCM,25 °C反应 24 h. [b] 分离收率;[c] 通过手性HPLC分析。
向反应管中添加膦配体L(12 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(5mol%)。排空烧瓶并重新注入氮气。将DCM(2ml)添加到管中,并在室温下搅拌0.5 h。然后在氮气气氛下,依次添加乙烯基苯并恶嗪酮1a(0.1 mmol),3-吡咯基羟吲哚2a(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,并使用石油醚/乙酸乙酯(5/1-3/1)作为洗脱剂在硅胶上通过快速柱色谱法纯化残留物,以得到所需产品,结果参见表1。
在表1中L17反应的基础上,将溶剂DCM替换为表2的溶剂,反应结果见表2。
表2 不同溶剂的反应结果
在表2中THF反应的基础上,采用不同原料摩尔比,反应结果见表3。
表3 不同原料比例的反应结果
在表3中1.5∶1反应的基础上,采用不同催化剂摩尔量,反应结果见表4。
表4 不同催化剂用量的反应结果
[d] Pd2(dba)3替换Pd2(dba)3·CHCl3。
以L17、Pd2(dba)3·CHCl3为催化体系、THF为溶剂进行以下底物拓展实验。
实施例一
表4中第2组反应,得29.6 mg黄色固体3aa,收率为90%,114-115 ℃。
对产物3aa进行分析,结果如下:99% ee [Daicel Chiralcel AD-H, hexanes/i-PrOH = 80/20, flow rate: 1.0 mL•min–1, λ = 254.4 nm, major enantiomer tr =17.261 min minor enantiomer tr = 30.446 min.]; [α]25 D= +197.24 (c 0.29,CHCI3); 1H NMR (400 MHz, CDCl3) δ 8.25 (s, 1H), 7.41 (d, J = 7.5 Hz, 1H),7.32 (td, J = 7.7, 1.3 Hz, 1H), 7.16 – 7.09 (m, 1H), 7.02 (td, J = 7.7, 1.5Hz, 1H), 6.97 (dd, J = 7.7, 1.6 Hz, 1H), 6.91 (d, J = 8.0 Hz, 1H), 6.88 (t, J= 2.2 Hz, 2H), 6.66 (t, J = 7.5 Hz, 1H), 6.57 (d, J = 7.9 Hz, 1H), 6.40 (d, J= 15.6 Hz, 1H), 6.21 (t, J = 2.2 Hz, 2H), 5.67 (dt, J = 15.2, 7.4 Hz, 1H),3.45 (s, 2H), 3.28 (ddd, J = 13.2, 6.8, 1.4 Hz, 1H), 3.20 (dd, J = 13.2, 8.0Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 176.1, 143.6, 140.7, 132.0, 130.1, 128.6,128.0, 127.4, 125.8, 123.3, 123.0, 122.9, 119.0, 118.7, 115.8, 110.7, 109.0,66.8, 40.7.
FT-IR: ν (cm-1): 3377, 1721, 1619, 1600, 1473, 1263, 1227, 1176,1097, 1074, 970, 746, 609.
HRMS (ESI): m/z: [M+H]+ Calcd. for C21H20N3O: 330.1601, found308.1605.
以上数据证明目的产物合成成功。
实施例二
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h。然后在氮气气氛下,依次添加1b(1.5当量),3-吡咯基羟吲哚2a(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(5/1-3/1)柱层析分离,得32.6mg黄色固体3ab收率为95%,137-138 °C。
对产物3ab进行分析,结果如下: 98% ee [Daicel Chiralcel AS-H, hexanes/i-PrOH = 85/15, flow rate: 1.0 mL•min–1, λ = 254.4 nm, major enantiomer tr =29.397 min minor enantiomer tr = 14.491 min.]; [α]25 D= +96.83 (c 0.41,CHCI3); 1H NMR (400 MHz, CDCl3) δ 8.39 (s, 1H), 7.41 (d, J = 7.5 Hz, 1H),7.33 (td, J = 7.8, 1.2 Hz, 1H), 7.13 (t, J = 7.6 Hz, 1H), 6.96 – 6.91 (m,2H), 6.90 (d, J = 2.2 Hz, 2H), 6.86 (d, J = 7.8 Hz, 1H), 6.59 (t, J = 7.5 Hz,1H), 6.43 (d, J = 15.5 Hz, 1H), 6.22 (t, J = 2.2 Hz, 2H), 5.67 (dt, J = 15.3,7.4 Hz, 1H), 3.34 – 3.25 (m, 1H), 3.19 (dd, J = 13.2, 8.0 Hz, 1H), 2.10 (s,3H); 13C NMR (101 MHz, CDCl3) δ 176.4, 141.8, 140.8, 132.5, 130.0, 129.8,128.0, 125.7, 125.4, 123.1, 123.0, 122.9, 122.3, 119.1, 118.0, 110.8, 108.9,66.8, 40.7, 17.5.
FT-IR: ν (cm-1): 3408, 3318, 1716, 1619, 1471, 1263, 1174, 1104, 974,754, 715.
HRMS (ESI): [M+H]+ Calcd. For C22H22N3O: 344.1758, found 344.1758.
以上数据证明目的产物合成成功。
实施例三
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h。然后在氮气气氛下,依次添加1c(1.5当量),3-吡咯基羟吲哚2a(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(5/1-3/1)柱层析分离,得29.6mg黄色液体3ac,收率85%。
对产物3ac进行分析,结果如下: 99% ee [Daicel Chiralcel AD-H, hexanes/i-PrOH = 80/20, flow rate: 1.0 mL·min–1, λ = 254.4 nm, major enantiomer tr =16.709 min mino enantiomer tr = 31.078 min.]; [α]25 D= +118.38 (c 0.37,CHCI3); 1H NMR (400 MHz, CDCl3) δ 7.96 (s, 1H), 7.41 (dd, J = 7.6, 1.2 Hz,1H), 7.34 (td, J = 7.7, 1.3 Hz, 1H), 7.14 (t, J = 7.7 Hz, 1H), 6.92 (d, J =7.9 Hz, 1H), 6.88 (p, J = 2.1 Hz, 3H), 6.37 – 6.25 (m, 3H), 6.21 (t, J = 2.2Hz, 2H), 5.60 (dt, J = 15.3, 7.5 Hz, 1H), 3.57 (s, 2H), 3.26 (ddd, J = 13.2,6.9, 1.4 Hz, 1H), 3.18 (dd, J = 13.2, 8.0 Hz, 1H).; 19F NMR (376 MHz, CDCl3)δ -113.9; 13C NMR (101 MHz, CDCl3) δ 176.5, 163.2 (d, J= 245.4 Hz), 145.2 (d,J=11.1 Hz), 140.8, 131.1, 130.1, 128.7 (d, J= 10.1 Hz), 128.0, 125.6, 123.0,122.8, 119.2(d, J= 2.0 Hz), 119.0, 110.8, 109.0, 105.3(d, J= 21.2 Hz), 102.1(d, J= 24.2 Hz ), 66.9, 40.5.
FT-IR: ν (cm-1): 3359, 2919, 2850, 1717, 1619, 1502, 1471, 1261,1166, 1098, 973, 721.
HRMS (ESI): m/z: [M+H]+ Calcd. for C21H19FN3O: 348.1507, found348.1510.
以上数据证明目的产物合成成功。
实施例四
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1d(1.5当量),3-吡咯基羟吲哚2a(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(5/1-3/1)柱层析分离,得33mg黄色固体3ad,收率91%,55-56℃。
对产物3ad进行分析,结果如下: >99% ee [Daicel Chiralcel AD-H, hexanes/i-PrOH = 80/20, flow rate: 1.0 mL•min–1, λ = 254.4 nm, major enantiomer tr =19.328 min.]; [α]25 D= +111.22 (c 0.41, CHCI3); 1H NMR (400 MHz, CDCl3) δ8.75 (s, 1H), 7.37 (d, J = 7.6 Hz, 1H), 7.32 (t, J = 7.8 Hz, 1H), 7.12 (t, J= 7.6 Hz, 1H), 6.88 (q, J = 8.1 Hz, 4H), 6.63 – 6.52 (m, 2H), 6.31 (d, J =15.6 Hz, 1H), 6.24 – 6.14 (m, 2H), 5.63 (dt, J = 15.2, 7.5 Hz, 1H), 3.24 (dd,J = 13.2, 6.9 Hz, 1H), 3.16 (dd, J = 13.2, 8.0 Hz, 1H), 2.87 (s, 2H); 13C NMR(101 MHz, CDCl3) δ 176.4, 144.6, 140.8, 133.9, 131.0, 130.1, 128.4, 128.0,125.6, 123.5, 123.0, 121.6, 119.0, 118.6, 115.3, 110.9, 109.0, 66.8, 40.5.
FT-IR: ν (cm-1): 3392, 3187, 2920, 2849, 1717, 1619, 1471, 1419,1260, 1225, 1097, 970, 799, 721.
HRMS (ESI): m/z: m/z: [M+Na]+ Calcd. for C21H18ClN3ONa: 386.1031,found 386.1032.
以上数据证明目的产物合成成功。
实施例五:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1e(1.5当量),3-吡咯基羟吲哚2a(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/丙酮(5/1-3/1)柱层析分离,得33.5mg黄色固体3ae,收率82%,53-54℃。
对产物3ae进行分析,结果如下: 99% ee [Daicel Chiralcel AD-H, hexanes/i-PrOH = 80/20, flow rate: 1.0 mL·min–1, λ = 254.4 nm, major enantiomer tr =22.155 min minor enantiomer tr = 37.901 min.]; [α]25 D= +87.62 (c 0.42,CHCI3); 1H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 15.2 Hz, 1H), 7.40 (d, J = 7.5Hz, 1H), 7.34 (td, J = 7.7, 1.3 Hz, 1H), 7.14 (td, J = 7.6, 1.0 Hz, 1H), 6.92(d, J = 7.8 Hz, 1H), 6.88 (t, J = 2.2 Hz, 2H), 6.80 (d, J = 8.1 Hz, 1H), 6.75(dd, J = 8.1, 1.9 Hz, 1H), 6.72 (d, J = 1.9 Hz, 1H), 6.29 (d, J = 15.6 Hz,1H), 6.21 (t, J = 2.2 Hz, 2H), 5.65 (dt, J = 15.2, 7.4 Hz, 1H), 3.26 (ddd, J= 13.2, 7.0, 1.4 Hz, 1H), 3.19 (dd, J = 13.2, 8.0 Hz, 1H).; 13C NMR (101 MHz,CDCl3) δ 175.8, 144.8, 140.6, 131.1, 130.2, 128.7, 127.9, 125.8, 123.6,123.0, 122.1, 121.5,119.1, 118.2, 110.7, 110.6, 109.0, 66.6, 40.7.
FT-IR: ν (cm-1): 3365, 2920, 2850, 1718, 1619, 1471, 1260, 1094, 722.
HRMS (ESI): m/z: [M+Na]+ Calcd. for C21H18BrN3ONa: 432.0505, found432.0505.
以上数据证明目的产物合成成功。
实施例六:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1f(1.5当量),3-吡咯基羟吲哚2a(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(6/1-3/1)柱层析分离,得31.4mg黄色固体3ae,收率79%,115-116℃。
对产物3af进行分析,结果如下: 99% ee [Daicel Chiralcel AD-H, hexanes/i-PrOH = 80/20, flow rate: 1.0 mL•min–1, λ = 254.4 nm, major enantiomer tr =10.895 min mino enantiomer tr = 18.880 min.]; [α]25 D= +111.91 (c 0.47,CHCI3); 1H NMR (400 MHz, CDCl3) δ 8.85 (d, J = 26.1 Hz, 1H), 7.39 (d, J = 7.5Hz, 1H), 7.33 (t, J = 7.7 Hz, 1H), 7.14 (t, J = 7.6 Hz, 1H), 7.02 (d, J = 8.0Hz, 1H), 6.94 – 6.84 (m, 4H), 6.77 (s, 1H), 6.38 (d, J = 15.6 Hz, 1H), 6.23(d, J = 2.4 Hz, 2H), 5.73 (dt, J = 15.3, 7.5 Hz, 1H), 3.66 (s, 2H), 3.28 (dd,J = 13.3, 6.9 Hz, 1H), 3.20 (dd, J = 13.3, 8.0 Hz, 1H).; 19F NMR (376 MHz,CDCl3) δ -62.8; 13C NMR (101 MHz, CDCl3) δ 176.4, 143.8, 140.7, 131.0, 130.5(q, J=32.3 Hz), 130.2, 127.9, 127.7, 126.1, 125.6, 125.1, 124.0(q, J= 273.7Hz), 123.1, 119.0, 114.9(q, J= 3Hz), 112.0(q, J= 3Hz), 110.9, 109.1, 66.8,40.5.
FT-IR: ν (cm-1): 3193, 2920, 2849, 1719, 1620, 1472, 1434, 1334 ,1256,1163, 1116, 971, 808, 721.
HRMS (ESI): m/z: [M+Na]+ Calcd. for C22H18F3N3ONa: 420.1295, found420.1292.
以上数据证明目的产物合成成功。
实施例七:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1g(1.5当量),3-吡咯基羟吲哚2a(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(5/1-3/1)柱层析分离,得24mg黄色固体3ag,收率70%,148-149℃。
对产物4ag进行分析,结果如下:99% ee [Daicel Chiralcel IA-H, hexanes/i-PrOH = 85/15, flow rate: 1.0 mL·min–1, λ = 254.4 nm, major enantiomer tr =13.615 min minor enantiomer tr = 32.841 min.]; [α]25 D= +114.58 (c 0.48,CHCI3); 1H NMR (400 MHz, CDCl3) δ 8.91 (s, 1H), 7.39 (d, J = 7.4 Hz, 1H), 7.31(t, J = 7.7 Hz, 1H), 7.12 (t, J = 7.6 Hz, 1H), 6.92 – 6.80 (m, 5H), 6.53 (d,J = 7.9 Hz, 1H), 6.43 (d, J = 15.6 Hz, 1H), 6.21 (t, J = 2.2 Hz, 2H), 5.66(dt, J = 15.2, 7.3 Hz, 1H), 3.30 (s, 2H), 3.28 – 3.23 (m, 1H), 3.19 (dd, J =13.2, 8.1 Hz, 1H), 2.18 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 176.7, 140.9,140.2, 132.1, 130.1, 129.3, 128.6, 128.1, 127.8, 125.6, 123.9, 123.0, 122.9,119.1, 116.6, 111.0, 109.0, 67.0, 40.6, 20.5.
FT-IR: ν (cm-1): 3373, 2920, 2849, 1708, 1619, 1470, 1264, 1097, 969,727.
HRMS (ESI): m/z: [M+H]+ Calcd. for C22H22N3O: 344.1758, found 344.1755.
以上数据证明目的产物合成成功。
实施例八:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1h(1.5当量),3-吡咯基羟吲哚2a(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(5/1-3/1)柱层析分离,得30.9mg黄色固体3ah,收率85%,150-151℃。
对产物3ah进行分析,结果如下: 99% ee [Daicel Chiralcel IA-H, hexanes/i-PrOH = 90/10, flow rate: 1.0 mL·min–1, λ = 254.4 nm, major enantiomer tr =13.793 min minor enantiomer tr = 36.693 min.]; [α]25 D= +48 (c 0.35, CHCI3); 1H NMR (400 MHz, CDCl3) δ 7.75 (s, 1H), 7.41 (d, J = 7.5 Hz, 1H), 7.35 (t, J =7.7 Hz, 1H), 7.15 (t, J = 7.6 Hz, 1H), 6.99 – 6.94 (m, 1H), 6.93 (d, J = 7.7Hz, 2H), 6.89 (s, 2H), 6.50 (d, J = 8.5 Hz, 1H), 6.32 (d, J = 15.6 Hz, 1H),6.21 (d, J = 2.8 Hz, 2H), 5.68 (dt, J = 15.3, 7.5 Hz, 1H), 3.47 (s, 2H), 3.27(dd, J = 13.3, 7.0 Hz, 1H), 3.19 (dd, J = 13.2, 8.0 Hz, 1H); 13C NMR (101 MHz,CDCl3) δ 176.1, 142.2, 140.7, 130.9, 130.2, 128.3, 127.9, 126.9, 125.7,124.6, 124.2, 123.2, 123.0, 119.0, 116.9, 110.8, 109.1, 66.7, 40.6.
FT-IR: ν (cm-1): 3366, 3186, 2920, 2849, 1717, 1647, 1619, 1471, 1417,1260, 1226, 1094, 970, 880, 809, 721.
HRMS (ESI): m/z: [M+Na]+ Calcd. for C21H18ClN3ONa: 386.1031, found386.1030.
以上数据证明目的产物合成成功。
实施例九:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1i(1.5当量),3-吡咯基羟吲哚2a(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(5/1-3/1)柱层析分离,得34mg黄色固体3ai,收率85%,143-144℃。
对产物3ai进行分析,结果如下:99% ee [Daicel Chiralcel AD-H,hexanes/i-PrOH = 80/20, flow rate: 1.0 mL·min–1, λ = 254.4 nm, major enantiomer tr =14.426 min minorenantiomer tr = 40.914 min]; [α]25 D= +108.33 (c 0.36,CHCI3); 1H NMR (400 MHz, DMSO-d6) δ 10.73 (s, 1H), 7.40 (dt, J = 7.5, 0.9 Hz,1H), 7.33 (td, J = 7.7, 1.2 Hz, 1H), 7.09 (td, J = 7.6, 1.1 Hz, 1H), 7.02(dd, J = 8.6, 2.4 Hz, 1H), 6.94 (dt, J = 7.8, 0.8 Hz, 1H), 6.87 (d, J = 2.4Hz, 1H), 6.83 (t, J = 2.2 Hz, 2H), 6.53 (s, 1H), 6.49 (d, J = 15.9 Hz, 1H),6.06 (t, J = 2.2 Hz, 2H), 5.50 (ddd, J = 15.1, 7.8, 6.7 Hz, 1H), 5.08 (s,2H), 3.29 (ddd, J = 13.2, 7.5, 1.7 Hz, 1H), 3.11 (ddd, J = 13.2, 7.9, 1.1 Hz,1H); 13C NMR (101 MHz, DMSO) δ 175.29, 144.95, 141.80, 130.68, 130.01, 129.96,128.56, 127.92, 125.28, 123.25, 122.54, 122.29, 118.88, 117.17, 110.30,108.46, 106.99, 66.40, 39.74.
FT-IR: ν (cm-1): 3361, 2920, 2850, 1706, 1609, 1491, 1469, 1350, 1231,1093, 970, 747.
HRMS (ESI): m/z: [M+H]+ Calcd. for C21H18BrN3O: 408.0706, found408.0705.
以上数据证明目的产物合成成功。
实施例十:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1j(1.5当量),3-吡咯基羟吲哚2a(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(5/1-3/1)柱层析分离,得25.1mg黄色固体3aj,收率73%,117-118℃。
对产物3aj进行分析,结果如下:98% ee [Daicel Chiralcel AS-H, hexanes/i-PrOH = 80/20, flow rate: 1.0 mL•min–1, λ = 254.4 nm, minor enantiomer tr =21.633 min major enantiomer tr = 26.914 min.]; [α]25 D= +101.94 (c 0.31,CHCI3); 1H NMR (400 MHz, CDCl3) δ 8.56 (s, 1H), 7.42 (d, J = 7.5 Hz, 1H), 7.31(t, J = 7.7 Hz, 1H), 7.13 (t, J = 7.6 Hz, 1H), 6.94 – 6.89 (m, 1H), 6.89 –6.86 (m, 3H), 6.51 (d, J = 7.5 Hz, 1H), 6.42 (d, J = 8.0 Hz, 1H), 6.32 (d, J= 16.1 Hz, 1H), 6.21 (t, J = 2.2 Hz, 2H), 5.55 (dt, J = 15.5, 7.3 Hz, 1H),3.50 – 3.34 (m, 3H), 3.28 (dd, J = 13.2, 7.7 Hz, 1H), 2.02 (s, 3H); 13C NMR(101 MHz, CDCl3) δ 176.4, 143.9, 140.8, 136.8, 131.8, 130.1, 129.9, 128.1,127.7, 126.8, 125.5, 123.1, 122.6, 120.0, 118.9, 113.0, 110.9, 109.0, 66.7,41.1, 20.3.
FT-IR: ν (cm-1): 3392, 3374, 3319, 2920, 2849, 1703, 1619, 1465, 1331,1289, 1265, 1218, 1167, 1099, 983, 798, 693.
HRMS (ESI): m/z: [M+H]+ Calcd. for C22H22N3O: 344.1758, found 344.1753.
以上数据证明目的产物合成成功。
实施例十一:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1k(1.5当量),3-吡咯基羟吲哚2a(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(5/1-3/1)柱层析分离,得32.6mg黄色液体3ak, 收率90%。
对产物3ak分析,结果如下:99% ee [Daicel Chiralcel AS-H, hexanes/i-PrOH= 80/20, flow rate: 1.0 mL·min–1, λ = 254.4 nm,] minor enantiomer tr = 31.108min major enantiomer tr = 39.846 min.; [α]25 D = +84.15 (c 0.41, CHCl3); 1HNMR (400 MHz, CDCl3) δ 8.99 (s, 1H), 7.42 (dd, J = 7.6, 1.2 Hz, 1H), 7.32(td, J = 7.8, 1.3 Hz, 1H), 7.13 (td, J = 7.6, 1.0 Hz, 1H), 6.93 (d, J = 7.8Hz, 1H), 6.89 – 6.84 (m, 3H), 6.67 (dd, J = 7.9, 1.1 Hz, 1H), 6.43 (dd, J =8.1, 1.1 Hz, 1H), 6.36 (d, J = 16.2 Hz, 1H), 6.21 (t, J = 2.2 Hz, 2H), 5.72(dt, J = 16.2, 7.3 Hz, 1H), 3.59 (s, 2H), 3.38 (ddd, J = 13.4, 7.1, 1.4 Hz,1H), 3.29 (ddd, J = 13.4, 7.6, 1.3 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 176.6,145.4, 140.7, 133.8, 130.1, 130.0, 128.4, 128.2, 128.0, 125.6, 123.3, 121.1,118.9, 118.9, 113.6, 110.9, 109.1, 66.6, 41.0.
FT-IR: ν (cm-1): 3374, 2920, 2851, 1716, 1619, 1567, 1471, 1289, 1263,1235.16, 1175.35, 1097.56, 975.79, 787.72, 752.08, 717.79, 621.87.
HRMS (ESI): m/z: [M+H]+ Calcd. for C21H18ClN3O: 364.1212, found364.1218.
以上数据证明目的产物合成成功。
实施例十二:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1l(1.5当量),3-吡咯基羟吲哚2a(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(5/1-3/1)柱层析分离,得25.1mg黄色固体3al,收率98%,125-126℃。
对产物3al分析,结果如下: 99% ee [Daicel Chiralcel AS-H, hexanes/i-PrOH= 85/15, flow rate: 1.0 mL·min–1, λ = 254.4 nm, minor enantiomer tr = 18.989min major enantiomer tr = 29.478 min.]; [α]25 D = +141.14 (c 0.44, CHCl3); 1HNMR (400 MHz, CDCl3) δ 8.25 (s, 1H), 7.41 (d, J = 7.5 Hz, 1H), 7.32 (t, J =7.7 Hz, 1H), 7.12 (t, J = 7.6 Hz, 1H), 6.94 – 6.85 (m, 3H), 6.76 (d, J = 7.7Hz, 1H), 6.52 (d, J = 7.7 Hz, 1H), 6.40 (d, J = 15.5 Hz, 1H), 6.21 (t, J =2.2 Hz, 2H), 5.63 (dt, J = 15.2, 7.4 Hz, 1H), 3.45 (s, 2H), 3.28 (dd, J =13.2, 6.9 Hz, 1H), 3.19 (dd, J = 13.2, 8.0 Hz, 1H), 2.22 (s, 3H), 2.01 (s,3H); 13C NMR (101 MHz, CDCl3) δ 176.4, 141.7, 140.8, 136.6, 132.7, 130.0,128.0, 125.7, 124.4, 122.9, 122.5, 121.2, 120.6, 120.1, 119.1, 110.8, 108.9,66.9, 40.7, 20.6, 12.8.
FT-IR: ν (cm-1): 3399, 3335, 2920, 1723, 1617, 1471, 1260, 1170, 1097,971, 805, 756, 675.
HRMS (ESI): m/z: [M+Na]+ Calcd. for C23H23N3ONa:380.1734, found380.1734.
以上数据证明目的产物合成成功。
实施例十三:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1a(1.5当量),2b(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/丙酮(5/1-3/1)柱层析分离,得29mg黄色固体3ba,收率98%,140-141℃。
对产物3ba分析,结果如下: >99% ee [Daicel Chiralcel AD-H, hexanes/i-PrOH = 80/20, flow rate: 1.0 mL·min–1, λ = 254.4 nm, major enantiomer tr =13.728 min.]; [α]25 D = +37.78 (c 0.36, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.95(s, 1H), 7.22 (t, J = 8.0 Hz, 1H), 7.05 (d, J = 8.2 Hz, 1H), 7.00 (td, J =7.6, 1.6 Hz, 1H), 6.89 (dd, J = 7.6, 1.6 Hz, 1H), 6.77 – 6.72 (m, 3H), 6.64(td, J = 7.5, 1.1 Hz, 1H), 6.57 – 6.51 (m, 2H), 6.22 (t, J = 2.2 Hz, 2H),5.54 (dt, J = 15.3, 7.5 Hz, 1H), 3.67 (ddd, J = 12.5, 7.2, 1.2 Hz, 1H), 3.49– 3.42 (m, 1H), 2.84 (s, 2H).; 13C NMR (101 MHz, CDCl3) δ 175.9, 143.2, 142.7,131.8, 131.4, 128.8, 128.7, 127.4, 125.1, 124.2, 123.3, 122.5, 118.9, 118.5,116.0, 109.4, 109.0, 68.0, 36.6.
FT-IR: ν (cm-1): 3393, 2920, 2849, 1720, 1615, 1451, 1260, 1101, 719.
HRMS (ESI): m/z: [M+Na]+ Calcd. for C21H18ClN3ONa: 386.1031, found386.1032.
以上数据证明目的产物合成成功。
实施例十四:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1a(1.5当量),2c(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/丙酮(5/1-3/1)柱层析分离,得24.5mg黄色固体3ca,收率60%,130-131℃。
对产物3ca分析,结果如下:> 99% ee [Daicel Chiralcel AD-H, hexanes/i-PrOH = 80/20, flow rate: 1.0 mL·min–1, λ = 254.4 nm, major enantiomer tr =14.35 min. ]; [α]25 D = +40.95 (c 0.21, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.69(s, 1H), 7.24 (d, J = 8.2 Hz, 1H), 7.16 (t, J = 7.9 Hz, 1H), 7.01 (td, J =7.6, 1.6 Hz, 1H), 6.88 (dd, J = 7.7, 1.6 Hz, 1H), 6.80 (d, J = 7.7 Hz, 1H),6.74 (t, J = 2.2 Hz, 2H), 6.63 (t, J = 7.5 Hz, 1H), 6.59 – 6.51 (m, 2H), 6.23(t, J = 2.2 Hz, 2H), 5.54 (dt, J = 15.3, 7.5 Hz, 1H), 3.81 – 3.73 (m, 1H),3.42 (dd, J = 12.5, 7.7 Hz, 1H).; 13C NMR (101 MHz, CDCl3) δ 175.9, 143.5,142.9, 131.8, 131.5, 128.7, 127.4, 127.4, 126.8, 123.1, 122.4, 120.5, 118.7,118.6, 115.8, 109.8, 109.1, 68.6, 36.3.
FT-IR: ν (cm-1): 3394, 2920, 2849, 1718, 1613, 1448, 1260, 1081, 970,720, 647.
HRMS (ESI): m/z: [M+H]+ Calcd. for C21H19BrN3O: 408.0706, found408.0708.
以上数据证明目的产物合成成功。
实施例十五:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1a(1.5当量),2d(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(5/1-3/1)柱层析分离,得28.1mg黄色固体3da,收率81%,126-127℃。
对产物3da分析,结果如下:99% ee [Daicel Chiralcel AS-H, hexanes/i-PrOH= 80/20, flow rate: 1.0 mL·min–1, λ = 254.4 nm, minor enantiomer tr = 23.374min. major enantiomer tr = 34.3 min.]; [α]25 D = +80 (c 0.28, CHCl3); 1H NMR(400 MHz, CDCl3) δ 8.53 (s, 1H), 7.13 (dd, J = 7.7, 2.6 Hz, 1H), 7.03 (td, J= 8.7, 2.4 Hz, 2H), 6.98 (dd, J = 7.7, 1.5 Hz, 1H), 6.84 (t, J = 2.2 Hz, 2H),6.82 (d, J = 4.2 Hz, 1H), 6.67 (td, J = 7.5, 1.2 Hz, 1H), 6.58 (dd, J = 8.0,1.2 Hz, 1H), 6.46 (d, J = 15.6 Hz, 1H), 6.22 (t, J = 2.2 Hz, 2H), 5.64 (ddd,J = 15.3, 8.1, 6.7 Hz, 1H), 3.56 (s, 2H), 3.26 (ddd, J = 13.3, 6.8, 1.4 Hz,1H), 3.19 (ddd, J = 13.3, 8.1, 1.1 Hz, 1H).; 19F NMR (376 MHz, CDCl3) δ -118.7; 13C NMR (101 MHz, CDCl3) δ 176.3, 159.0 (d, J= 243.4 Hz), 143.6, 136.6(d, J= 3 Hz), 132.3, 129.7 (d, J= 8.1 Hz), 128.8, 127.4, 123.1, 122.3, 118.9,118.7, 116.7 (d, J= 23.2 Hz), 115.9, 113.4 (d, J= 25.3 Hz), 111.5 (d, J= 8.1Hz), 109.3, 67.2 (d, J= 2.0 Hz), 40.5.
FT-IR: ν (cm-1): 3393, 2920, 2850, 1716, 1645, 1486, 1259,1185, 1099,971, 815, 721.
HRMS (ESI): m/z: [M+H]+ Calcd. for C21H19FN3O: 348.1507, found348.1510.
以上数据证明目的产物合成成功。
实施例十六:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1a(1.5当量),2e(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(5/1-3/1)柱层析分离,得33.8mg黄色固体3ea,收率93%,132-133℃。
对产物3ea分析,结果如下: 99% ee [Daicel Chiralcel AS-H, hexanes/i-PrOH= 80/20, flow rate: 1.0 mL·min–1, λ = 254.4 nm,]; [α]25 D = +50.59 (c 0.34,CHCl3); 1H NMR (400 MHz, CDCl3)δ 8.74 (s, 1H), 7.37 (d, J = 2.1 Hz, 1H), 7.29(dd, J = 8.4, 2.1 Hz, 1H), 7.04 (td, J = 7.7, 1.5 Hz, 1H), 6.99 (dd, J = 7.7,1.5 Hz, 1H), 6.85 – 6.78 (m, 3H), 6.68 (t, J = 7.5 Hz, 1H), 6.62 – 6.55 (m,1H), 6.46 (d, J = 15.6 Hz, 1H), 6.22 (t, J = 2.2 Hz, 2H), 5.63 (ddd, J =15.2, 8.2, 6.6 Hz, 1H), 3.57 (s, 2H), 3.29 – 3.22 (m, 1H), 3.18 (dd, J =13.3, 8.2 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 176.2, 143.6, 139.2, 132.4,130.1, 129.9, 128.8, 128.4, 127.4, 125.7, 123.1, 122.2, 118.9, 118.8, 115.9,111.9, 109.3, 67.0, 40.5.
FT-IR: ν (cm-1): 3317, 2920, 2850, 1714, 1619, 1471, 1435, 1263, 1171,1104, 1080, 973, 818, 752, 643.
HRMS (ESI): m/z: [M+Na]+ Calcd. for C21H18ClN3ONa: 386.1031, found386.1038.
以上数据证明目的产物合成成功。
实施例十七:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1a(1.5当量),2f(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(5/1-3/1)柱层析分离,得35.1mg黄色固体3fa,收率86%,159-160℃。图1为3fa溶解在三氯甲烷形成的黄色溶液。
对产物3fa分析,结果如下: 99% ee [Daicel Chiralcel AS-H, hexanes/i-PrOH= 80/20, flow rate: 1.0 mL·min–1, λ = 254.4 nm, minor enantiomer tr = 20.619min. major enantiomer tr = 31.144 min.]; [α]25 D = +35.46 (c 0.44, CHCl3); 1HNMR (400 MHz, CDCl3) δ 8.63 (s, 1H), 7.51 (d, J = 2.0 Hz, 1H), 7.44 (dd, J =8.3, 2.0 Hz, 1H), 7.07 – 7.01 (m, 1H), 6.99 (d, J = 7.5 Hz, 1H), 6.83 (t, J =2.2 Hz, 2H), 6.77 (d, J = 8.3 Hz, 1H), 6.68 (t, J = 7.5 Hz, 1H), 6.59 (d, J =7.9 Hz, 1H), 6.46 (d, J = 15.6 Hz, 1H), 6.23 (t, J = 2.2 Hz, 2H), 5.63 (dt, J= 15.2, 7.4 Hz, 1H), 3.56 (s, 2H), 3.25 (dd, J = 13.3, 6.8 Hz, 1H), 3.18 (dd,J = 13.3, 8.2 Hz, 1H).13C NMR (101 MHz, CDCl3) δ 175.9, 143.6, 139.7, 133.0,132.5, 130.3, 128.8, 128.5, 127.4, 123.1, 122.2, 118.9, 118.7, 115.9, 115.6,112.3, 109.4, 67.0, 40.5.
FT-IR: ν (cm-1): 3445, 3376, 3066, 2923, 2852, 1715, 1618, 1472, 1454,1290, 1263, 1103, 970, 819, 756.
HRMS (ESI): m/z: [M+Na]+ Calcd. for C21H18BrN3ONa: 430.0526, found430.0532.
以上数据证明目的产物合成成功。
实施例十八:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1a(1.5当量),2g(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(5/1-3/1)柱层析分离,得24mg黄色固体3ga,收率70%,160-161℃。
对产物3ga分析,结果如下:99% ee [Daicel Chiralcel AS-H, hexanes/i-PrOH= 80/20, flow rate: 1.0 mL·min–1, λ = 254.4 nm, minor enantiomer tr = 17.784min. major enantiomer tr = 25.003 min.; [α]25 D = +52.4 (c 0.25, CHCl3); 1HNMR (400 MHz, DMSO-d6) δ 10.61 (s, 1H), 7.23 (d, J = 1.7 Hz, 1H), 7.14 – 7.10(m, 1H), 6.89 (ddd, J = 8.3, 7.2, 1.6 Hz, 1H), 6.85 – 6.79 (m, 4H), 6.60 –6.51 (m, 2H), 6.42 (td, J = 7.4, 1.2 Hz, 1H), 6.06 (t, J = 2.2 Hz, 2H), 5.44(ddd, J = 15.1, 7.9, 6.6 Hz, 1H), 4.83 (s, 2H), 3.27 (ddd, J = 13.1, 6.6, 1.4Hz, 1H), 3.11 (dd, J = 13.2, 7.9 Hz, 1H), 2.28 (s, 3H); 13C NMR (101 MHz,DMSO) δ 175.3, 145.4, 139.3, 131.2, 131.1, 130.1, 128.7, 128.3, 125.9, 125.6,121.2, 121.0, 118.8, 116.4, 115.2, 110.0, 108.3, 66.5, 20.8.
13C DEPT-135 NMR (101 MHz, DMSO) δ 40.2 (CH2).
FT-IR: ν (cm-1): 3393, 3194, 2920, 2849, 1716, 1624, 1492, 1260, 1097,971, 720.
HRMS (ESI): m/z: [M+H]+ Calcd. for C22H22N3O: 344.1758, found 344.1757.
以上数据证明目的产物合成成功。
实施例十九:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1a(1.5当量),2h(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/丙酮(5/1-3/1)柱层析分离,得19.7mg黄色液体3ha,收率55%。
对产物3ha分析,结果如下: >99% ee [Daicel Chiralcel AS-H, hexanes/i-PrOH = 80/20, flow rate: 1.0 mL·min–1, λ = 254.4 nm, major enantiomer tr =47.977 min.]; [α]25 D = +43.33 (c 0.24, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.33(s, 1H), 6.97 – 6.88 (m, 3H), 6.79 (t, J = 2.2 Hz, 2H), 6.77 – 6.71 (m, 2H),6.58 (td, J = 7.5, 1.1 Hz, 1H), 6.49 (dd, J = 8.0, 1.2 Hz, 1H), 6.37 (d, J =15.6 Hz, 1H), 6.14 (t, J = 2.2 Hz, 2H), 5.57 (ddd, J = 15.2, 8.1, 6.6 Hz,1H), 3.69 (s, 3H), 3.45 (s, 2H), 3.21 – 3.09 (m, 2H); 13C NMR (101 MHz, CDCl3)δ 176.3, 156.0, 143.7, 134.0, 132.1, 129.3, 128.7, 127.5, 123.3, 123.0,119.1, 118.7, 115.8, 115.0, 112.2, 111.3, 109.1, 77.4, 77.1, 76.7, 67.4,55.9, 40.6.
FT-IR: ν (cm-1): 3393, 2920, 2849, 1715, 1645, 1488, 1260, 1203, 1027,972, 721.
HRMS (ESI): m/z: [M+H]+ Calcd. for C22H22N3O2: 360.1707, found360.1712.
以上数据证明目的产物合成成功。
实施例二十:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1a(1.5当量),2i(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(5/1-3/1)柱层析分离,得26.6mg黄色固体3ia,收率71%,170-171 ℃.
对产物3ia分析,结果如下:>99% ee [Daicel Chiralcel AS-H, hexanes/i-PrOH= 80/20, flow rate: 1.0 mL·min–1, λ = 254.4 nm,] major enantiomer tr = 23.945min.; [α]25 D = +13.33 (c 0.27, CHCl3);1H NMR (400 MHz, DMSO-d6) δ 11.44 (s,1H), 8.32 – 8.21 (m, 2H), 7.13 (d, J = 8.4 Hz, 1H), 6.91 (t, J = 2.2 Hz, 2H),6.90 – 6.86 (m, 1H), 6.82 (dd, J = 7.7, 1.6 Hz, 1H), 6.63 – 6.53 (m, 2H),6.41 (t, J = 7.4 Hz, 1H), 6.10 (t, J = 2.2 Hz, 2H), 5.47 (ddd, J = 15.1, 8.0,6.6 Hz, 1H), 4.87 (s, 2H), 3.55 – 3.46 (m, 1H), 3.18 (dd, J = 13.2, 8.0 Hz,1H).;) 13C NMR (101 MHz, DMSO) δ 175.7, 148.0, 145.5, 142.6, 131.9, 129.8,128.4, 127.0, 125.9, 120.8, 120.7, 119.8, 119.0, 116.3, 115.3, 110.6, 108.8,66.4. 13C DEPT-135 NMR (101 MHz, DMSO) δ 39.6 (CH2).
FT-IR: ν (cm-1): 3390, 2920, 2850, 1721, 1623, 1519, 1455, 1337, 1256,1090, 799, 640.
HRMS (ESI): m/z: [M+H]+ Calcd. for C21H19N4O3: 375.1452, found375.1451.
以上数据证明目的产物合成成功。
实施例二十一:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1a(1.5当量),2j(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(5/1-3/1)柱层析分离,得27.1mg黄色液体3ja,收率78%.
对产物3ja分析,结果如下:>99% ee [Daicel Chiralcel AD-H, hexanes/i-PrOH = 80/20, flow rate: 1.0 mL·min–1, λ = 254.4 nm, major enantiomer tr =16.935 min.]; [α]25 D = +83.45 (c 0.29, CHCl3); 1H NMR (400 MHz, DMSO-d6) δ10.87 (s, 1H), 7.43 (dd, J = 8.4, 5.4 Hz, 1H), 6.92 – 6.86 (m, 2H), 6.83 (p,J = 2.3 Hz, 3H), 6.76 (dd, J = 9.0, 2.5 Hz, 1H), 6.59 – 6.51 (m, 2H), 6.43(td, J = 7.4, 1.2 Hz, 1H), 6.07 (t, J = 2.2 Hz, 2H), 5.46 (ddd, J = 15.1,7.8, 6.7 Hz, 1H), 4.87 (s, 2H), 3.32 – 3.27 (m, 1H), 3.10 (dd, J = 13.3, 7.9Hz, 1H); 19F NMR (376 MHz, CDCl3) δ -110.2; 13C NMR (101 MHz, DMSO) δ 176.0,164.4(d, J= 245.4Hz), 144.0(d, J= 12.1 Hz), 145.9, 131.8, 128.8, 127.4(d, J=10.1 Hz), 124.9(d, J= 3.0 Hz), 126.3, 121.5, 121.0, 119.2, 116.9, 115.7,108.9(d, J= 23.2 Hz), 99.4(d, J= 27.3 Hz ), 66.5. 13C DEPT-135 NMR (101 MHz,DMSO) δ 40.1 (CH2).
FT-IR: ν (cm-1): 2921, 2852, 1727, 1617, 1458, 1260, 1142, 1099, 963,804, 721.
HRMS (ESI): m/z: [M+H]+ Calcd. for C21H19FN3O: 348.1507, found348.1506.
以上数据证明目的产物合成成功。
实施例二十二:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1a(1.5当量),2k(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(5/1-3/1)柱层析分离,得29.1mg黄色液体3ja,收率80%.87-88 ℃.
对产物3ka分析,结果如下: >99% ee [Daicel Chiralcel AD-H, hexanes/i-PrOH = 80/20, flow rate: 1.0 mL·min–1, λ = 254.4 nm,] major enantiomer tr =16.156 min.; [α]25 D = +92.26 (c 0.31, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.77(s, 1H), 7.30 (d, J = 8.0 Hz, 1H), 7.10 (dd, J = 8.1, 1.9 Hz, 1H), 7.07 –6.98 (m, 2H), 6.91 (d, J = 1.9 Hz, 1H), 6.84 (t, J = 2.3 Hz, 2H), 6.68 (t, J= 7.5 Hz, 1H), 6.59 (d, J = 8.0 Hz, 1H), 6.43 (d, J = 15.5 Hz, 1H), 6.25 –6.20 (m, 2H), 5.71 – 5.59 (m, 1H), 3.54 (s, 2H), 3.27 (dd, J = 13.2, 6.6 Hz,1H), 3.15 (dd, J = 13.4, 8.2 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 176.4, 143.5,141.9, 135.9, 132.2, 128.8, 127.3, 126.6, 126.4, 123.1, 123.0, 122.4, 118.9,118.8, 115.9, 111.5, 109.3, 66.5, 40.5.
FT-IR: ν (cm-1): 3392, 3197, 2920, 2849, 1722, 1614, 1455, 1261, 1069,971, 924, 721.
HRMS (ESI): m/z: [M+Na]+ Calcd. for C21H18ClN3ONa: 386.1031, found348.1021.
以上数据证明目的产物合成成功。
实施例二十三:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1a(1.5当量),2l(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(5/1-3/1)柱层析分离,得30.6mg黄色液体3la,收率75%.67-68 ℃.
对产物3la分析,结果如下:> 99% ee [Daicel Chiralcel AD-H, hexanes/i-PrOH = 80/20, flow rate: 1.0 mL·min–1, λ = 254.4 nm, major enantiomer tr =16.759 min.]; [α]25 D = +92.88 (c 0.66, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.56(s, 1H), 7.28 (d, J = 1.5 Hz, 1H), 7.24 (s, 1H), 7.09 – 6.97 (m, 3H), 6.83(t, J = 2.3 Hz, 2H), 6.68 (td, J = 7.5, 1.2 Hz, 1H), 6.59 (dd, J = 7.9, 1.2Hz, 1H), 6.42 (d, J = 15.6 Hz, 1H), 6.22 (t, J = 2.2 Hz, 2H), 5.65 (ddd, J =15.2, 8.2, 6.6 Hz, 1H), 3.26 (ddd, J = 13.3, 6.6, 1.5 Hz, 1H), 3.19 – 3.10(m, 1H); 13C NMR (101 MHz, CDCl3) δ 176.1, 143.6, 142.0, 132.3, 128.8, 127.3,127.0, 126.9, 125.9, 123.8, 123.1, 122.4, 118.9, 118.8, 115.9, 114.2, 109.3,66.6, 40.4.
FT-IR: ν (cm-1): 3212, 2922, 2851,1722, 1609, 1480, 1260 ,1097, 1058,970, 806, 721.
HRMS (ESI): m/z: [M+H]+ Calcd. for C21H19BrN3O: 408.0706, found408.0702.
以上数据证明目的产物合成成功。
实施例二十四:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1a(1.5当量),2m(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/丙酮(5/1-3/1)柱层析分离,得22.3mg黄色固体3ma,收率62%.122-123 ℃.
对产物3ma分析,结果如下:> 99% ee [Daicel Chiralcel AS-H, hexanes/i-PrOH = 80/20, flow rate: 1.0 mL·min–1, λ = 254.4 nm, major enantiomer tr =36.814 min.]; [α]25 D = +147.27 (c 0.22, CHCl3); 1H NMR (400 MHz, CDCl3) δ8.42 (s, 1H), 7.29 (d, J = 8.4 Hz, 1H), 7.05 – 6.98 (m, 2H), 6.88 (t, J = 2.3Hz, 2H), 6.71 – 6.61 (m, 2H), 6.58 (d, J = 7.9 Hz, 1H), 6.48 (d, J = 2.3 Hz,1H), 6.42 (d, J = 15.6 Hz, 1H), 6.20 (t, J = 2.3 Hz, 2H), 5.74 – 5.60 (m,1H), 3.81 (s, 3H), 3.51 (s, 2H), 3.30 – 3.21 (m, 1H), 3.15 (dd, J = 13.3, 8.1Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 176.8, 161.3, 143.6, 142.1, 131.8, 128.6,127.4, 126.6, 123.3, 123.2, 119.6, 119.0, 118.7, 115.8, 108.8, 107.8, 97.7,66.5, 55.6, 40.8.
FT-IR: ν (cm-1): 3389, 3186, 2919, 2848, 1722, 1633, 1456, 1421, 1333,1255, 1153, 1127, 1094, 1025, 966, 852, 797, 647.
HRMS (ESI): m/z: [M+H]+ Calcd. for C22H22N3O2: 360.1707, found360.1696.
以上数据证明目的产物合成成功。
实施例二十五:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1a(1.5当量),2n(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(5/1-3/1)柱层析分离,得30mg黄色固体3na,收率87%.75-76 ℃.
对产物3na分析,结果如下:99% ee [Daicel Chiralcel AS-H, hexanes/i-PrOH= 80/20, flow rate: 1.0 mL·min–1, λ = 254.4 nm, major enantiomer tr = 10.329min. minor enantiomer tr = 12.921 min.]; [α]25 D = +127.37 (c 0.38, CHCl3);1HNMR (400 MHz, CDCl3) δ 9.15 (s, 1H), 7.24 (s, 1H), 7.15 (d, J = 7.7 Hz, 1H),7.08 – 6.96 (m, 3H), 6.90 (t, J = 2.3 Hz, 2H), 6.70 – 6.64 (m, 1H), 6.57 (dd,J = 8.0, 1.1 Hz, 1H), 6.41 (d, J = 15.6 Hz, 1H), 6.20 (t, J = 2.2 Hz, 2H),5.69 (ddd, J = 15.2, 8.0, 6.8 Hz, 1H), 3.48 (s, 2H), 3.28 (ddd, J = 13.3,6.8, 1.4 Hz, 1H), 3.16 (dd, J = 13.3, 8.1 Hz, 1H), 2.27 (s, 3H); 13C NMR (101MHz, CDCl3) δ 177.0, 143.6, 139.6, 131.9, 131.3, 128.5, 127.5, 127.4, 123.4,123.3, 123.1, 122.8, 120.3, 119.1, 118.6, 115.7, 108.8, 67.2, 40.8, 14.1.
FT-IR: ν (cm-1): 3393, 2919, 2849, 1716, 1625, 1457, 1260, 1097, 971 ,720.
HRMS (ESI): m/z: [M+H]+ Calcd. for C22H22N3O: 344.1758, found 344.1748.
以上数据证明目的产物合成成功。
实施例二十六:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1a(1.5当量),2o(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(5/1-3/1)柱层析分离,得26.4mg黄色固体3oa,收率76%.63-64 ℃.
对产物3oa分析,结果如下:99% ee [Daicel Chiralcel OD-H, hexanes/i-PrOH= 70/30, flow rate: 1.0 mL·min–1, λ = 254.4 nm, minor enantiomer tr = 11.25min. major enantiomer tr = 22.66 min.]; [α]25 D = +82.12 (c 0.33, CHCl3); 1HNMR (400 MHz, CDCl3) δ 7.63 (s, 1H), 7.22 (s, 1H), 7.16 – 7.08 (m, 2H), 7.04(t, J = 7.6 Hz, 1H), 6.99 (d, J = 7.5 Hz, 1H), 6.87 (t, J = 2.3 Hz, 2H), 6.67(t, J = 7.5 Hz, 1H), 6.61 (d, J = 8.0 Hz, 1H), 6.43 (d, J = 15.6 Hz, 1H),6.22 (t, J = 2.3 Hz, 2H), 5.67 (dt, J = 15.3, 7.5 Hz, 1H), 3.51 (s, 2H), 3.30(dd, J = 13.3, 6.7 Hz, 1H), 3.20 (dd, J = 13.4, 8.1 Hz, 1H); 19F NMR (376 MHz,CDCl3) δ -132.6; 13C NMR (101 MHz, CDCl3) δ 175.2, 147.2 (d, J= 246.4 Hz),143.6, 132.3, 130.6(d, J= 3 Hz), 128.7, 128.3 (d, J=13.1 Hz), 127.3, 123.6(d, J= 6.1 Hz), 123.2, 122.5, 121.4 (d, J= 3.0 Hz), 119.0, 118.7, 117.0 (d, J= 16.2 Hz), 115.9, 109.2, 67.0(d, J= 3.0 Hz), 40.7.
FT-IR: ν (cm-1): 3187, 2920, 2849, 1726, 1644, 1491, 1259, 1098, 971,721.
HRMS (ESI): m/z: [M+H]+ Calcd. for C21H19FN3O: 348.1507, found348.1515.
以上数据证明目的产物合成成功。
实施例二十七:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1a(1.5当量),2p(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(5/1-3/1)柱层析分离,得34.1mg黄色固体3pa,收率86%.61-62 ℃.
对产物3pa分析,结果如下:99% ee [Daicel Chiralcel OD-H, hexanes/i-PrOH= 70/30, flow rate: 1.0 mL·min–1, λ = 254.4 m, minor enantiomer tr = 12.237min. major enantiomer tr = 21.815 min.]; [α]25 D = +110.59 (c 0.34, CHCl3);1HNMR (400 MHz, CDCl3) δ 8.43 (s, 1H), 7.59 (t, J = 8.0 Hz, 2H), 7.23 (t, J =7.9 Hz, 1H), 7.08 – 7.02 (m, 1H), 7.00 – 6.95 (m, 1H), 6.88 (t, J = 2.3 Hz,2H), 6.68 (t, J = 7.5 Hz, 1H), 6.61 (d, J = 8.0 Hz, 1H), 6.45 (d, J = 15.6Hz, 1H), 6.24 (t, J = 2.3 Hz, 2H), 5.75 – 5.64 (m, 1H), 3.35 (dd, J = 13.5,6.7 Hz, 1H), 3.18 – 3.12 (m, 1H).; 19F NMR (376 MHz, CDCl3) δ -60.7; 13C NMR(101 MHz, CDCl3) δ 175.5, 143.6, 138.3(q, J= 2.0 Hz), 132.6, 129.7, 129.3,128.9, 127.4, 126.9(q, J= 4.0 Hz), 123.6(q, J= 272.7 Hz ), 123.1, 122.8,122.2, 119.0, 118.9, 116.0, 113.1(q, J= 33.0 Hz), 109.4, 65.8, 40.7.
FT-IR: ν (cm-1): 3393, 3190, 2920, 2849, 1733, 1619, 1457, 1303, 1166,1115, 798, 721.5.
HRMS (ESI): m/z: [M+H]+ Calcd. for C22H19F3N3O: 398.1475, found398.1479.
以上数据证明目的产物合成成功。
实施例二十八:
向反应管中添加手性草酰胺膦配体L(6 mol%)、三(二亚苄基丙酮)二钯-氯仿加合物(2.5 mol%)。排空烧瓶并重新注入氮气。将THF(2ml)添加到管中,并在室温下搅拌0.5 h.然后在氮气气氛下,依次添加1a(1.5当量),2q(0.1 mmol)。将反应混合物在25℃下搅拌24小时,然后在真空中浓缩混合物,体系直接用石油醚/乙酸乙酯(5/1-3/1)柱层析分离,得32.1mg黄色液体3qa,收率90%.
对产物3aa分析,结果如下:99% ee [Daicel Chiralcel AS-H, hexanes/i-PrOH= 80/20, flow rate: 1.0 mL·min–1, λ = 254.4 nm, major enantiomer tr = 8.895min. minor enantiomer tr = 10.93 min.]; [α]25 D = +43.23 (c 0.31, CHCl3); 1HNMR (400 MHz, DMSO-d6) δ 10.65 (s, 1H), 7.03 (s, 1H), 6.95 (d, J = 1.6 Hz,1H), 6.89 (ddd, J = 8.2, 7.3, 1.6 Hz, 1H), 6.83 (t, J = 2.2 Hz, 2H), 6.80(dd, J = 7.7, 1.6 Hz, 1H), 6.58 – 6.50 (m, 2H), 6.43 (td, J = 7.5, 1.2 Hz,1H), 6.05 (t, J = 2.2 Hz, 2H), 5.43 (ddd, J = 15.0, 7.9, 6.5 Hz, 1H), 4.83(s, 2H), 3.27 – 3.21 (m, 1H), 3.09 (dd, J = 13.2, 8.0 Hz, 1H), 2.24 (s, 3H),2.18 (s, 3H); 13C NMR (101 MHz, DMSO) δ 175.7, 145.4, 137.9, 131.5, 131.1,131.0, 128.4, 128.2, 126.0, 122.8, 121.3, 121.2, 119.3, 118.8, 116.3, 115.2,108.2, 66.7, 20.6, 16.3. 13C DEPT-135 NMR (101 MHz, DMSO) δ 40.3 (CH2).
FT-IR: ν (cm-1): 3185, 2920, 2850, 1716, 1625, 1482, 1260,1094, 800,721.
HRMS (ESI): m/z: [M+H]+ Calcd. for C23H24N3O: 358.1914, found 358.1909.
以上数据证明目的产物合成成功。
放大实验
参照实施例一、实施例十七的方法,原料用量放大10倍,也是较高收率、高Ee值得到产物,反应示意如下:
本发明公开了了一种简单、高效的合成结构复杂的手性吲哚酮类芳胺化合物的合成方法,该方法不仅要收率高、对映选择性优秀,同时所需底物易合成,廉价易得,催化剂催化效率高,反应条件温和,操作简单,因此符合绿色化学的要求。
Claims (10)
1.一种含有双取代吲哚酮骨架的芳胺化合物的合成方法,其特征在于,包括以下步骤:以3-吡咯基羟吲哚和乙烯基苯并恶嗪酮为反应物,在手性草酰胺膦配体、三(二亚苄基丙酮)二钯-氯仿加合物存在下,在有机溶剂中,反应得到含有双取代吲哚酮骨架的芳胺化合物。
2. 根据权利要求1所述的合成方法,其特征在于: 所述有机溶剂选自醚类溶剂、卤代烃类溶剂、苯类溶剂或者质子性溶剂。
3. 根据权利要求1所述的合成方法,其特征在于: 以摩尔量计,所述手性草酰胺膦配体的用量为3-吡咯基羟吲哚的5~12%,所述乙烯基苯并恶嗪酮用量为3-吡咯基羟吲哚的0.6~1 .5倍;所述三(二亚苄基丙酮)二钯-氯仿加合物的用量为3-吡咯基羟吲哚的2.5~5%。
5.根据权利要求1所述的合成方法,其特征在于:所述反应的时间为24~48小时;所述反应的温度为室温。
7.根据权利要求1所述的合成方法,其特征在于:所述反应结束后,经过柱层析得到产物。
10.根据权利要求1所述的合成方法制备的含有双取代吲哚酮骨架的芳胺化合物。
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