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  分子催化  2025, Vol. 39 Issue (4): 297-308
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引用本文 

孙彩玲, 刘源, 谢银君. 8-氨基喹哪啶衍生锰配合物催化苄醇与乙酰胺的脱氢烯基化反应[J]. 分子催化, 2025, 39(4): 297-308.
SUN Cailing, LIU Yuan, XIE Yinjun. 8-Aminoquinaldine-Derived Manganese Complex Catalyzed Dehydrogenative Olefination of Benzyl Alcohols with Acetamides[J]. Journal of Molecular Catalysis, 2025, 39(4): 297-308.

基金项目

宁波市3315计划创新团队(2020A-32-C); 宁波市自然科学基(2022J287) [3315 Program of Ningbo (2020A-32-C); Ningbo Natural Science Foundation (2022J287)].

作者简介

孙彩玲 (1999—), 女, 硕士研究生, 研究方向有机合成, E-mail: suncailing@nimte.ac.cn

通讯联系人

E-mail: xieyinjun@nimte.ac.cn

文章历史

收稿日期:2025-04-15
修回日期:2025-05-19
8-氨基喹哪啶衍生锰配合物催化苄醇与乙酰胺的脱氢烯基化反应
孙彩玲1,2 , 刘源1 , 谢银君1     
1. 中国科学院宁波材料技术与工程研究所 全省先进燃料电池与电解池技术重点实验室, 浙江 宁波 315201;
2. 中国科学院大学 化学科学学院, 北京 100190
摘要:官能团化烯烃是构筑生物活性分子和功能材料的关键模块. 本文创新性地设计并开发了一种基于8-氨基喹哪啶骨架的新型锰钳形配合物, 并通过X射线单晶衍射、核磁共振波谱和高分辨质谱等手段系统研究了金属配合物的结构. 以此锰配合物为催化剂, 实现了苄醇与酰胺的脱氢α-烯基化反应, 合成多种α,β-不饱和酰胺. 此外, 通过对比实验揭示了反应途径. 研究结果表明, 该催化体系具有良好的官能团兼容性和选择性, 且反应过程中只生成水和氢气等副产物, 为官能团化烯烃合成提供了一种绿色高效的新方法.
关键词锰催化剂    官能团化烯烃    不饱和酰胺    脱氢偶联    
8-Aminoquinaldine-Derived Manganese Complex Catalyzed Dehydrogenative Olefination of Benzyl Alcohols with Acetamides
SUN Cailing1,2 , LIU Yuan1 , XIE Yinjun1     
1. Zhejiang Province Key Laboratory of Advanced Fuel Cells and Electrolyzers Technology, Ningbo Institute of Materials Technology and Engineering of the Chinese Academy of Sciences (CAS), Ningbo 315201, China;
2. School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 100190, China
Abstract: Functionalized olefins are key building blocks for constructing bioactive molecules and functional materials. In this study, a novel manganese pincer complex based on an 8-aminoquinaldine skeleton was innovatively designed and synthesized. The structure of the Mn complex was systematically investigated by single crystal X-ray diffraction, nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. Based on this novel manganese complex, the dehydrogenative olefination of benzyl alcohols and amides was achieved, and a series of α,β-unsaturated amides were synthesized. In addition, the reaction pathway was elucidated through control experiments. This catalytic system has good functional group compatibility and selectivity, and the by-products generated in the reaction process are water and hydrogen, providing a green and efficient new method for the synthesis of functionalized alkenes.
Key words: manganese catalyst    functionalized olefins    unsaturated amides    dehydrogenative coupling    

官能团化烯烃, 尤其是α,β-不饱和烯烃, 是生物活性分子、药物和功能材料的重要结构单元[16](图1(a)). 因此, 官能团化烯烃的合成一直是有机化学的研究热点, 主要合成方法有Wittig反应[7]、Julia烯烃合成[810]和McMurry偶联[1112]等. 然而, 上述方法需要先将醇类化合物氧化为醛, 醛再与磷叶立德、硫叶立德等试剂反应, 存在步骤长、操作复杂等问题. 近年来, 铱[1314]、钌[15]、钯[16]、镍[1718]、铁[19]等金属催化醇的无受体脱氢偶联反应, 为直接从醇出发构建官能团化烯烃提供了新方法. 但是, 由于这些催化剂一般兼具催化加氢和脱氢活性, 容易导致烯基化产物被反应中生成的氢气还原而得到烷基化产物[2021], 尤其是当底物含酯基或酰胺等官能团时基本只得到烷基化产物[2223]. 例如, 醇与乙酰胺的脱氢偶联反应往往得到的是α-烷基化产物, 难以得到烯基化的α,β-不饱和酰胺[2427]. 因此, 通过开发高选择性催化剂实现醇与乙酰胺的脱氢烯基化直接合成α,β-不饱和乙酰胺类化合物, 对于拓展官能团化烯烃的分子多样性具有重要的意义.

图 1 锰催化剂的设计及其在醇脱氢烯基化合成官能团化烯烃中的应用 Fig.1 Mn catalyst design and application in dehydrogenative olefination

锰是地壳中丰度第三的过渡金属, 具有廉价、低毒和优异的生物相容性等优点[2830]. 通过合理的配体设计, 锰配合物可展现出丰富多样的催化活性, 使其成为贵金属催化剂的可持续替代品[31]. 因此, 锰催化剂的开发和锰催化的化学反应成为当前催化领域的研究热点之一[3236]. 锰催化的脱氢和加氢反应始于2016年[37], 经过近十年的发展, 已经可以实现对烯烃[3839]、亚胺[40]、醛[4142]、酮[4344]、酯[4546]和酰胺[4748]等化合物的选择性加氢, 也可以实现催化醇类化合物选择性脱氢合成酯[4950]、酰胺[5154]和烷基化[5558]的反应, 但是存在催化剂用量较高的问题. 据文献调研发现, Gunanathan等[59]报道了一例锰催化的醇与酰胺脱氢烯基化反应制备α,β-不饱和酰胺, 但是底物主要局限于二级酰胺, 三级酰胺的底物仅有3例(图1(b)). 因此, 发展高效的锰催化剂实现醇与三级酰胺的脱氢烯基化反应是挑战性的课题, 具有重要的研究意义.

基于课题组前期的研究基础, 以8-氨基喹哪啶作为原料, 设计合成了一种新型的三齿钳形配体, 将其与五羰基溴化锰反应合成了一种新型锰催化剂(图1(b)), 顺利实现了醇与乙酰胺的脱氢α-烯基化反应, 合成多种α,β-不饱和酰胺类化合物.

1 实验部分 1.1 试剂和仪器

所用苄醇均为分析纯试剂, 购于安徽泽升科技有限公司, 并经分子筛干燥以后使用; 酰胺通过已有报道进行合成[6062]; 8-氨基喹哪啶(分析纯)购于无锡鼎泰化工有限公司; 甲苯和1,4-二氧六环为分析纯试剂, 经金属钠干燥, 重蒸后使用. 其他分析纯试剂通过市售渠道购买后直接使用.

所用主要仪器包括: Bruker AVANCE Ⅲ 400 MHz和600 MHz核磁共振波谱仪(德国); Agilent 8860气相色谱(美国); Agilent 8860/5977B气相色谱-质谱联用仪(美国); Bruker MicroTOF-QⅡ mass instrument高分辨质谱仪(德国).

1.2 配体和锰催化剂合成

配体和锰催化剂的合成步骤如图2所示,配体L1-BH3由8-氨基喹哪啶经两步制备得到, 接着利用三乙烯二胺脱去配体L1-BH3上的硼烷保护基团, 再与五羰基溴化锰反应制备新型锰配合物Mn-1.

图 2 配体和锰催化剂的合成 Fig.2 Synthesis of ligands and manganese catalysts

a. 在氩气氛围下, 将8-氨基喹哪啶(10 mmol, 1.58 g)、碳酸钾(15 mmol, 2.07 g)、氯化苄(22 mmol, 2.53 mL)和异丙醇(20 mL)依次加入至100 mL三口烧瓶中, 在60 ℃下反应30 h. 经TCL检测反应完全后, 冷却至室温, 经过滤、浓缩、正己烷重结晶后得到淡黄色产物N-苄基-2-甲基喹啉, 收率为58%. N-苄基-2-甲基喹啉[63]: 1H NMR (600 MHz, CDCl3) δ 7.94 (d, J = 8.3 Hz, 1H), 7.45 (d, J = 7.6 Hz, 2H), 7.34 (t, J = 7.5 Hz, 2H), 7.28–7.23 (m, 3H), 7.01 (d, J = 8.1 Hz, 1H), 6.64 (bs, 1H), 6.61 (d, J = 7.6 Hz, 1H), 4.56 (s, 2H), 2.69 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 155.8, 144.3, 139.7, 137.7, 136.3, 128.7, 127.5, 127.2, 126.8, 126.7, 122.3, 114.2, 105.3, 47.8, 25.3.

b. 在氩气氛围下, 往带有磁子的100 mL两口瓶中加入N-苄基-2-甲基喹啉(6 mmol, 1.49 g)和THF(10 mL). 将反应置于−78 ℃ 下加入nBuLi(13.2 mmol, 5.5 mL), 10 min后恢复至室温再搅拌1 h. −78 ℃下将二异丙基氯化磷的THF溶液(7.2 mmol, 1.1 g in 10 mL THF)加入至反应液, 10 min后恢复至室温反应12 h. 经TCL检测反应完全后, 在0 ℃下加入硼烷四氢呋喃溶液(9 mmol, 9 mL), 继续反应12 h. 反应结束后加入水(1.5 mL)淬灭反应, 经萃取、浓缩、柱层析纯化得到L1-BH3, 分离收率为61%. L1-BH3: 31P NMR (162 MHz, CDCl3) δ 35.17; 1H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 8.4 Hz, 1H), 7.43–7.30 (m, 7H), 7.06 (d, J = 7.8 Hz, 2H), 6.69 (d, J = 7.6 Hz, 1H), 6.35 (s, 1H), 4.52 (s, 2H), 3.40 (d, J = 10.9 Hz, 2H), 2.17–2.04 (m, 2H), 1.17–1.08 (m, 12H), 0.73–0.26 (m, 3H); 13C NMR (151 MHz, CDCl3) δ 152.0 (d, J = 7.6 Hz), 144.2, 139.3, 137.6, 136.6, 128.8, 127.7, 127.4, 127.2, 123.2 (d, J = 3.0 Hz), 114.2, 105.4, 47.9, 31.2, 31.0, 22.0, 21.8, 17.1 (d, J = 10.6 Hz); HRMS (ESI) calcd. for C23H30N2P, [M-BH3+H]+: 365.2147, found: 365.2127.

c. 在氮气气氛手套箱中, 将L1-BH3 (0.5 mmol, 189 mg)、三乙烯二胺(1 mmol, 112 mg)和THF(4 mL)依次加至25 mL杨氏管后, 在70 ℃下搅拌12 h. 反应结束后, 减压浓缩, 经正己烷洗涤、过滤并浓缩后得到L1, 再加入五羰基溴化锰(0.33 mmol, 91 mg)和THF (3 mL)在70 ℃下反应48 h. 反应液冷却至室温后减压浓缩, 所得固体经正己烷和甲基叔丁基醚洗涤后, 离心、干燥, 得到配合物Mn-1, 收率为77%. 最后, 通过核磁、X射线单晶衍射等手段对配体及其配合物结构进行了表征. Mn-1: 31P NMR (162 MHz, CDCl3) δ 110.75; 1H NMR (600 MHz, CDCl3) δ 8.10 (d, J = 7.6 Hz, 1H), 7.67 (d, J = 7.2 Hz, 1H), 7.57 (s, 3H), 7.50–7.46 (m, 3H), 7.38 (d, J = 6.5 Hz, 2H), 5.72 (s, 1H), 5.08 (d, J = 14.1 Hz, 1H), 4.74–4.71 (m, 1H), 3.80–3.68 (m, 2H), 2.90 (d, J = 6.3 Hz, 1H), 2.41–2.37 (m, 1H), 1.48–1.44 (m, 3H), 1.33–1.30 (m, 3H), 1.22–1.18 (m, 3H), 1.08–1.05 (m, 3H); 13C NMR (151 MHz, CDCl3) δ 146.5, 138.3, 136.2, 129.2, 128.0, 127.6, 127.3, 126.4, 125.7, 124.7, 120.9, 60.3, 41.7 (d, J = 15.1 Hz), 29.8 (d, J = 18.1 Hz), 25.6 (d, J = 22.7 Hz), 20.0, 19.3, 18.7, 18.5 (d, J = 6.0 Hz); HRMS (ESI) calcd. for C25H29MnN2O2P, [M-Br]+: 475.1347, found: 475.1320.

1.3 醇与酰胺的α-烯基化反应

在氮气氛围手套箱中, 将甲醇锂(1.6 mmol, 60.8 mg)、Mn-1(0.05 mmol, 27.8 mg)和1,4-二氧六环(1 mL)依次加至带有磁力搅拌子的10 mL干燥Schlenk管中, 搅拌20 min后, 再加入苯甲醇(1 mmol, 108 mg)、N-甲基乙酰苯胺(2 mmol, 298 mg)及1,4-二氧六环(1 mL). 将Schlenk管从手套箱中取出, 放置于120 ℃油浴锅中加热回流, 同时缓慢通入氩气. 反应36 h后, 停止加热, 冷却至室温, 经柱层析纯化分离得3a3p.

产物核磁数据如下:

N,N-二甲基肉桂酰胺(3a)[64]: 白色固体; 总分离收率为48%; 通过GC检测得3a/4a值为86/14; 1H NMR (600 MHz, CDCl3) δ 7.68 (d, J = 15.5 Hz, 1H), 7.53–7.51 (m, 2H), 7.36–7.35 (m, 3H), 6.90 (d, J = 15.4 Hz, 1H), 3.15 (s, 3H), 3.05 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 166.6, 142.2, 135.3, 129.5, 128.8, 127.7, 117.5, 37.4, 35.9.

3-(4-叔丁基苯基)-N,N-二甲基丙烯酰胺(3b)[64]: 白色固体; 总分离收率为45%, 3b/4b值为83/17; 1H NMR (600 MHz, CDCl3) δ 7.68 (d, J = 15.4 Hz, 1H), 7.48–7.46 (m, 2H), 7.39–7.38 (m, 2H), 6.88 (d, J = 15.8 Hz, 1H), 3.15 (s, 3H), 3.05 (s, 3H), 1.32 (s, 9H); 13C NMR (151 MHz, CDCl3) δ 166.8, 152.9, 142.1, 132.6, 127.6, 125.7, 116.6, 37.4, 35.9, 34.7, 31.4.

3-(4-氯苯基)-N,N-二甲基丙烯酰胺(3c)[64]: 白色固体; 总分离收率为50%, 通过GC检测得3c/4c 值为71/29; 1H NMR (600 MHz, CDCl3) δ 7.62 (d, J = 15.4 Hz, 1H), 7.45–7.44 (m, 2H), 7.33–7.32 (m, 2H), 6.88 (d, J = 15.4 Hz, 1H), 3.16 (s, 3H), 3.06 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 166.3, 140.8, 135.2, 133.8, 129.0, 128.9, 118.0, 37.4, 35.9.

N-苯基肉桂酰胺(3d)[65]: 白色固体; 总分离收率为51%; 通过GC检测得3d/4d值为97/3; 1H NMR (600 MHz, CDCl3) δ 7.77 (d, J = 15.4 Hz, 1H), 7.64–7.62 (m, 2H), 7.53–7.47 (m, 3H), 7.38–7.34 (m, 5H), 7.15–7.13 (m, 1H), 6.58 (d, J = 15.4 Hz, 1H); 13C NMR (151 MHz, CDCl3) δ 164.1, 142.6, 138.2, 134.8, 130.1, 129.2, 129.0, 128.1, 124.6, 121.0, 120.1.

N,N-二乙基肉桂酰胺(3e)[64]: 无色液体; 总分离收率为52%, 通过GC检测得3e/4e 值为93/7; 1H NMR (600 MHz, CDCl3) δ 7.72 (d, J = 15.4 Hz, 1H), 7.53–7.51 (m, 2H), 7.38–7.33 (m, 3H), 6.84 (d, J = 15.2 Hz, 1H), 3.51–3.46 (m, 4H), 1.25–1.19 (m, 6H); 13C NMR (151 MHz, CDCl3) δ 165.7, 142.3, 135.6, 129.5, 128.8, 127.8, 117.9, 42.3, 41.1, 15.1, 13.3.

1-哌啶基-3-苯基- 2-丙烯-1-酮(3f)[64]: 白色固体; 总分离收率为36%; 通过GC检测得3f/4f值为80/20; 1H NMR (600 MHz, CDCl3) δ 7.65 (d, J = 15.1 Hz, 1H), 7.52–7.51 (m, 2H), 7.38–7.30 (m, 3H), 6.92 (d, J = 15.5 Hz, 1H), 3.65–3.55 (m, 4H), 1.68–1.59 (m, 6H); 13C NMR (151 MHz, CDCl3) δ 165.4, 142.2, 135.6, 129.4, 128.8, 127.7, 117.9, 47.1, 43.4, 26.8, 25.7, 24.7.

1-吗啉基-3-苯基-2-丙烯-1-酮(3g)[64]: 白色固体; 总分离收率为64%; 通过GC检测得3g/4g值为85/15; 1H NMR (600 MHz, CDCl3) δ 7.71 (d, J = 15.4 Hz, 1H), 7.53–7.52 (m, 2H), 7.39–7.34 (m, 3H), 6.86 (d, J = 15.4 Hz, 1H), 3.72–3.70 (m, 8H); 13C NMR (151 MHz, CDCl3) δ 165.7, 143.3, 135.3, 129.9, 128.9, 127.9, 116.7, 67.0, 46.3, 42.7.

N-乙基-N-苯基肉桂酰胺(3h)[66]: 白色固体; 总分离收率为45%; 通过GC检测得3h/4h值为90/10; 1H NMR (600 MHz, CDCl3) δ 7.68 (d, J = 15.5 Hz, 1H), 7.46–7.43 (m, 2H), 7.39–7.37 (m, 1H), 7.28–7.26 (m, 5H), 7.22–7.20 (m, 2H), 6.29 (d, J = 15.5 Hz, 1H), 3.91–3.88 (m, 2H), 1.18 (t, J = 7.2 Hz, 3H); 13C NMR (151 MHz, CDCl3) δ 165.7, 142.1, 141.7, 135.4, 129.7, 129.5, 128.8, 128.5, 127.9, 127.9, 119.3, 44.6, 13.2.

N,N-二苄基肉桂酰胺(3i)[67]: 白色固体; 总分离收率为40%; 通过GC检测得3i/4i值为94/6; 1H NMR (600 MHz, CDCl3) δ 7.87 (d, J = 15.3 Hz, 1H), 7.47–7.45 (m, 2H), 7.39–7.33 (m, 11H), 7.23–7.22 (m, 2H), 6.91 (d, J = 15.4 Hz, 1H), 4.71 (s, 2H), 4.61 (s, 2H); 13C NMR (151 MHz, CDCl3) δ 167.3, 144.0, 137.5, 136.9, 135.3, 129.9, 129.1, 128.9, 128.8, 128.5, 128.0, 127.9, 127.6, 126.7, 117.4, 50.2, 49.0.

N-甲基-N-苯基肉桂酰胺(3j)[68]: 无色液体; 总分离收率为60%; 通过GC检测得3j/4j值为46/54; 1H NMR (600 MHz, CDCl3) δ 7.70 (d, J = 15.4 Hz, 1H), 7.45–7.42 (m, 2H), 7.38–7.36 (m, 1H), 7.31–7.27 (m, 5H), 7.24–7.22 (m, 2H), 6.39 (d, J = 15.5 Hz, 1H), 3.41 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 166.2, 143.7, 141.7, 135.3, 129.8, 129.6, 128.7, 127.9, 127.7, 127.4, 118.9, 37.6.

3-(对甲苯基)-N-甲基-N-苯基丙烯酰胺(3k)[68]: 白色固体; 总分离收率为56%; 通过GC检测得3k/4k值为63/37; 1H NMR (600 MHz, CDCl3) δ 7.67 (d, J = 15.4 Hz, 1H), 7.44–7.41 (m, 2H), 7.30–7.28 (m, 1H), 7.23–7.20 (m, 4H), 7.08–7.07 (m, 2H), 6.34 (d, J = 15.4 Hz, 1H), 3.40 (s, 3H), 2.30 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 166.4, 143.8, 141.7, 139.8, 132.5, 129.6, 129.4, 127.9, 127.5, 127.4, 117.8, 37.6, 21.4.

3-(4-叔丁基苯基)-N-甲基-N-苯基丙烯酰胺(3l): 无色液体; 总分离收率为62%; 通过GC检测得3l/4l值为72/28; 1H NMR (600 MHz, CDCl3) δ 7.69 (d, J = 15.4 Hz, 1H), 7.43–7.40 (m, 2H), 7.35–7.33 (m, 2H), 7.30–7.25 (m, 5H), 6.36 (d, J = 15.4 Hz, 1H), 3.40 (s, 3H), 1.27 (s, 9H); 13C NMR (151 MHz, CDCl3) δ 166.3, 152.9, 143.7, 141.5, 132.5, 129.6, 128.1, 127.6, 127.5, 127.3, 125.6, 118.0, 37.5, 31.1; HRMS (ESI) calcd. for C20H24NO [M+H]: 294.1858, found: 294.1861.

3-(4-甲氧基苯基)-N-甲基-N-苯基丙烯酰胺(3m)[68]: 白色固体; 总分离收率为61%; 通过GC检测得3m/4m值为95/5; 1H NMR (600 MHz, CDCl3) δ 7.65 (d, J = 15.4 Hz, 1H), 7.45–7.41 (m, 2H), 7.37–7.34 (m, 1H), 7.27–7.23 (m, 4H), 6.81–6.79 (m, 2H), 6.25 (d, J = 15.5 Hz, 1H), 3.78 (s, 3H), 3.41 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 166.6, 160.9, 143.9, 141.4, 129.7, 129.5, 128.1, 127.6, 127.5, 116.5, 114.2, 55.4, 37.6.

3-(3,4,5-三甲氧基苯基)-N-甲基-N-苯基丙烯酰胺(3n): 白色固体; 总分离收率为71%; 通过GC检测得3n/4n值为95/5; 1H NMR (600 MHz, CDCl3) δ 7.60 (d, J = 16.2 Hz, 1H), 7.45–7.43 (m, 2H), 7.37–7.35 (m, 1H), 7.26–7.24 (m, 2H), 6.53 (s, 2H), 6.26 (d, J = 15.5 Hz, 1H), 3.83 (s, 3H), 3.79 (s, 6H), 3.42 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 166.2, 153.4, 143.8, 141.7, 139.7, 131.0, 129.7, 127.7, 127.5, 118.4, 105.2, 61.0, 56.2, 37.7; HRMS (ESI) calcd. for C19H22NO4 [M+H]: 328.1549, found: 328.1555.

3-(4-氯苯基)-N-甲基-N-苯基丙烯酰胺(3o)[68]: 白色固体; 总分离收率为48%; 通过GC检测得3o/4o值为77/23; 1H NMR (600 MHz, CDCl3) δ 7.64 (d, J = 15.5 Hz, 1H), 7.46–7.44 (m, 2H), 7.39–7.31 (m, 1H), 7.25–7.23 (m, 6H), 6.35 (d, J = 15.4 Hz, 1H), 3.41 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 166.0, 143.6, 140.4, 135.4, 133.8, 129.8, 129.0, 128.5, 127.8, 127.4, 119.4, 37.7.

3-(4-溴苯基)-N-甲基-N-苯基丙烯酰胺(3p)[68]: 白色固体; 总分离收率为55%; 通过GC检测得3p/4p值为88/12; 1H NMR (600 MHz, CDCl3) δ 7.62 (d, J = 15.4 Hz, 1H), 7.46–7.37 (m, 5H), 7.23–7.22 (m, 2H), 7.17–7.15 (m, 2H), 6.36 (d, J = 15.8 Hz, 1H), 3.41 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 165.9, 143.6, 140.4, 134.2, 131.9, 129.9, 129.3, 127.8, 127.4, 123.6, 119.5, 37.7.

2 结果与讨论 2.1 配体与锰催化剂X射线单晶衍射表征

将8-氨基喹哪啶衍生的新配体与硼烷的配合物L1-BH3和锰配合物Mn-1利用二氯甲烷和正己烷进行结晶, 并通过X射线单晶衍射对其结构进行进一步表征. 如图3所示, L1-BH3的喹啉骨架8-位上为氮原子, 2-位则为通过亚甲基连接二异丙基膦, 硼烷与膦发生配位起到稳定配体的作用. 锰配合物的结构显示锰金属中心与8-氨基喹哪啶衍生的配体为1∶1配比, 锰金属分别与2个氮原子、1个磷原子和1个溴原子、2个一氧化碳形成六配位, 锰的化合物为正一价.

图 3 配体和锰配合物的X射线单晶衍射表征 Fig.3 Single-crystal X-ray diffraction analysis of the ligands and manganese catalysts
2.2 苄醇与酰胺α-烯基化反应条件优化

首先, 以苄醇(1a, 0.5 mmol)和N,N-二甲基乙酰胺(2a, 1 mmol)作为模板底物、甲醇锂作为碱(0.6 mmol)、甲苯作为溶剂, 在油浴130 ℃、氩气流下反应12 h, 考察催化剂前体对醇与酰胺脱氢α-烯基化反应的影响. 催化剂前体包括Mn-1和本课题组已报道的锰配合物[46]Mn-2Mn-3Mn-4(表1, Entry 1−4). 结果表明, 当以Mn-1(0.03 mmol)为催化剂时, 以7%的收率得到烯基化产物3a和13%的烷基化产物4a(表1, Entry 1); 采用Mn-2配合物为催化剂时, 主要得到烷基化产物4a(20%), 烯基化产物3a的收率仅为2%(表1, Entry 2); 而Mn-3Mn-4配合物则对该反应催化效果较差, 未检测到产物3a(表1, Entry 3−4). 通过GC-MS检测发现, 除产物3a4a外, 还有大量的副产物乙酸苄酯生成, 推测苄醇与N,N-二甲基乙酰胺发生了醇解反应, 导致苄醇转化率高但是产物选择性不佳.

表 1 苄醇与酰胺α-烯基化反应的条件优化a Table 1 Optimization of the reaction conditions for the α-alkenylation of alcohols with amidesa

随后, 使用Mn-1催化剂, 对反应温度进行考察, 发现当油浴温度降低至120 ℃时, 能以18%的收率得到产物3a, 且苄醇的转化率降低至63%, 表明适当降低反应温度能提高反应选择性(表1, Entry 5); 当油浴温度降低至110 ℃时, 目标产物3a收率仅为5%(表1, Entry 6). 在确定最佳反应温度为120 ℃后, 分别对碱的种类和用量进行考察, 包括甲醇钠、甲醇钾和氢化钠等碱(表1, Entry 7−14). 实验结果表明, 以甲醇锂为碱时, 反应效果最佳. 随后, 又对甲醇锂的用量进行考察, 当甲醇锂的量减少至0.3 mmol时, 3a产率仅为4%(表1, Entry 15); 而当甲醇锂的量增加至0.8 mmol时, 以24%的收率得到3a和6%的收率得到4a(表1, Entry 16). 当反应在1,4-二氧六环中进行时, 同样以24%的收率得到3a, 但烷基化的产物4a可降低至2%. 通过提高催化剂Mn-1的用量至醇的0.025 mmol, 并延长反应时间至36 h, 3a的收率可以顺利提高至51%, 其分离收率为48%(表1, Entry 19). 因此, 选定Mn-1 (0.025 mmol)为催化剂, 甲醇锂(0.8 mmol)为碱, 油浴120 ℃, 在氩气流下反应36 h为最佳反应条件.

2.3 苄醇与酰胺α-烯基化反应底物拓展

在确定最佳反应条件后, 对醇与酰胺的脱氢α-烯基化反应的底物范围进行了考察. 首先, 考察N,N-二甲基乙酰胺与取代苯甲醇的α-烯基化反应. 如表2所示, 分别以45%和50%的收率得到4-叔丁基(3b/4b=83/17)或4-氯取代(3c/4c=71/29)的α-烯基化和烷基化产物. 随后, 考察了不同取代乙酰胺对反应的影响, 当底物为二级酰胺乙酰苯胺时, 能以51%的收率和97%的烯基化选择性得到产物3d. 当底物为N,N-二乙基乙酰胺时, 能以52%的收率得到脱氢烯基化产物3e. 此外, 1-乙酰哌啶、4-乙酰基吗啉、N-乙基-N-苯基乙酰胺、N,N-二苄基乙酰胺和N-甲基-N-苯基乙酰胺等三级乙酰胺也能与苄醇进行脱氢烯基化反应, 以36%~64%的收率得到相应的烯基化产物3f3j. 最后, 以N-甲基-N-苯基乙酰胺考察了取代基对苯甲醇脱氢反应的影响, 发现含甲基、叔丁基、甲氧基和三甲氧基等苯甲醇作为底物时, 能以56%~71%的收率得到相应的产物. 值得注意的是, 当苯环上含三个给电子的甲氧基时, 能够最高以71%的收率得到烯基化产物3n, 给电子基团也能抑制α,β-不饱和酰胺的催化加氢. 当苯环上含吸电子取代基的4-氯苯甲醇和4-溴苯甲醇也能顺利转化, 分别以48%和55%的收率得到相应的脱氢偶联产物. 遗憾的是, 当以烷基醇作为底物时, 未观察到脱氢烯基化的产物.

表 2 苄醇与酰胺α-烯基化反应的底物范围考察a Table 2 Substrate scope for the α-alkenylation of alcohols with amidesa
2.4 反应机理研究

在进行底物适应性考察以后, 通过对比实验研究了催化反应机理. 首先, 以Mn-1作催化剂, 在催化量的甲醇锂存在条件下, 仅以苄醇作为底物, 120 ℃反应6 h后, 通过GC-MS检测观察到苯甲醛和苯甲酸苄酯的生成, 证明了脱氢反应的发生(图4, 方程式(1)). 其次, 在不添加Mn-1配合物、仅添加碱的条件下, 苄醇与N-甲基乙酰苯胺在120 ℃加热12 h未观察到产物3j4j(图4, 方程式(2)), 表明在没有锰配合物的条件下脱氢反应不发生. 再者, 不添加Mn-1配合物、仅添加碱的条件下苯甲醛能够与N-甲基乙酰苯胺反应时, 以23%的分离收率得到产物3j, 但未观察到4j的生成(图4, 方程式(3)), 表明碱性条件下乙酰胺能与醛发生缩合反应. 最后, 当反应中不加入碱时, 没有观察到3j4j的生成(图4, 方程式(4)), 推测未经碱活化的配合物Mn-1可能无法催化脱氢反应.

图 4 对比实验和反应路径 Fig.4 Control experiments and the reaction pathway

基于上述实验结果和文献基础[59, 6972], 推测醇与酰胺的反应途径如下: 首先, 经碱活化的锰配合物催化苄醇发生脱氢反应生成醛; 然后, 乙酰胺在碱的作用下发生去质子化生成亲核性的烯醇式Int-1, 再进攻醛基发生缩合反应生成中间体Int-2; 最后, 中间体Int-2发生消除反应生成产物3. 此外, 如果不能及时释放氢气, 产物3将在锰配合物的催化下发生加氢作用生成烷基化副产物4.

3 结论

综上所述, 本文设计并合成了一种基于8-氨基喹哪啶的新型锰钳形配合物Mn-NHNP, 通过核磁共振、单晶衍射等手段对配合物结构进行了详细的解析. 在此基础上, 以该锰配合物作为催化剂实现了醇与酰胺的α-烯基化反应, 制备了多种α,β-不饱和酰胺(40%~71%收率). 该反应具有良好的反应选择性和官能团兼容性, 且副产物仅为水和氢气, 为从简单的醇类化合物直接合成官能化烯烃提供了一种绿色高效的方法.

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