钯催化α-取代苄腈与支链烯丙基碳酸酯的烯丙基烷基化反应

张高鹏 江阳杰 丁昌华 侯雪龙

引用本文: 张高鹏, 江阳杰, 丁昌华, 侯雪龙. 钯催化α-取代苄腈与支链烯丙基碳酸酯的烯丙基烷基化反应[J]. 有机化学, 2020, 40(10): 3399-3409. doi: 10.6023/cjoc202006007 shu
Citation:  Zhang Gaopeng, Jiang Yangjie, Ding Changhua, Hou Xuelong. Palladium-Catalyzed Allylic Alkylation Reaction of α-Substituted Benzyl Nitriles with Branched Allyl Carbonates[J]. Chinese Journal of Organic Chemistry, 2020, 40(10): 3399-3409. doi: 10.6023/cjoc202006007 shu

钯催化α-取代苄腈与支链烯丙基碳酸酯的烯丙基烷基化反应

    通讯作者: 丁昌华, dingchanghua@shu.edu.cn; 侯雪龙, xlhou@sioc.ac.cn
  • 基金项目:

    国家自然科学基金(Nos.21532010,21772215),中国科学院先导项目(No.XDB20030100),中国科学院,上海市科委和香港裘搓基金会资助项目

摘要: 报道了钯催化下α-取代苄腈作为亲核试剂,与支链烯丙基碳酸酯的烯丙基烷基化反应,在易得的大位阻氮杂环卡宾配体存在下,以良好的收率、区域选择性及非对映选择性得到支链烯丙基烷基化产物.

English

  • 钯催化的烯丙基烷基化反应在有机化学中是一类非常重要的反应[1-2], 自1965年Tsuji等首次报道了钯参与的烯丙基烷基化反应之后, 这一反应就获得了极大的发展, 并成为构建碳碳键和碳杂键的最有效方法之一, 也在很多天然产物和生物活性分子的合成中发挥重要作用[2].通常认为, 不同的亲核试剂在钯催化的烯丙基烷基化反应中可能存在不同的反应历程.烯丙基试剂与钯发生氧化加成后生成π-烯丙基钯中间体, 亲核试剂进攻π-烯丙基钯中间体的端位碳原子(C1和C3), 得到相应的烯丙基烷基化的产物[3]; 或者亲核试剂进攻π-烯丙基钯中间体的金属钯中心, 然后发生还原消除同样得到烯丙基烷基化的产物(Scheme 1)[4].

    图式 1

    图式 1.  钯催化烯丙基烷基化反应
    Scheme 1.  Pd-catalyzed allylic alkylation

    在相当长的一段时间内, 钯催化烯丙基烷基化反应的研究大都围绕于亲核试剂进攻π-烯丙基钯中间体的端基碳原子进行[3, 5], 而对于通过亲核试剂进攻π-烯丙基钯中间体的金属钯来完成烯丙基烷基化反应的研究则不是很多[4].最近, Stoltz和Morken等[4c-4e]分别报道了烯丙基烯醇碳酸酯的钯催化脱羧烯丙基化和钯催化烯丙基硼酸酯与烯丙基试剂的交叉偶联反应.机理研究显示, 这些反应都是通过亲核试剂进攻钯进行的.我们课题组先后报道了亚胺及酮α-位碳负离子作为亲核试剂与单取代及端基二取代烯丙基试剂的钯催化烯丙基烷基化反应, 高区域选择性及非对映选择性地获得了相应产物, 并分别通过实验及密度泛函理论(DFT)研究证明, 亲核试剂进攻π-烯丙基钯中间体的金属钯中心, 再经钯参与的[3, 3']-还原消除机理[4h-4i].在以酮为亲核试剂的反应及相关研究中, 发现氮杂环卡宾(NHC)作为配体起了极其重要的作用.为了进一步拓展该Pd/NHC催化体系的底物适用范围, 发展更多的亲核试剂种类, 研究了以腈为亲核试剂的钯催化烯丙基烷基化反应.腈作为亲核试剂的钯催化烯丙基烷基化反应已有一些报道, 但是反应仍有很大的局限性, 诸如底物范围、反应的选择性控制, 尤其是与单取代烯丙基试剂反应时的区域选择性控制等[6].腈类化合物可以通过氰基α-位去质子后形成相应的碳负离子, 部分负电荷离域到氮原子上, 由此有可能使氮负离子作为亲核试剂进攻π-烯丙基钯中间体的金属钯, 通过随后的[3, 3']-还原消除反应得到预期的支链产物(Scheme 2).基于上述考虑, 我们使用苄腈类化合物作为亲核试剂, 在Pd/NHC催化体系下尝试了该烯丙基烷基化反应.

    图式 2

    图式 2.  Pd/NHC催化腈的烯丙基烷基化反应的可能反应历程
    Scheme 2.  Proposed reaction process of Pd/NHC catalyzed allylic alkylation of nitriles

    我们在之前的研究中发现, 乙腈化合物在碱的作用下会发生二聚[7a], 而使用α-烷基取代脂肪腈则得到环丙烷产物[7b].为了避免此类副反应的发生, 同时可以生成稳定的碳负离子, 选择了α-甲基苯乙腈1a作为亲核试剂进行研究.参考之前酮为亲核试剂的反应结果[4h-4i], 以[Pd(η3-C3H5)Cl]2为钯源, IPr•HCl (L1)为配体, LiHMDS为碱, 四氢呋喃为溶剂, 在室温下尝试α-甲基苯乙腈1a作为亲核试剂与苯基取代烯丙基试剂2a之间的反应, 结果以63%的收率得到直链烯丙基烷基化产物4a, 而支链产物3a产率仅为14%, 支链/直链(B/L)比仅为18/82, 支链产物的dr值为1.2:1(表 1, Entry 1).使用苯乙腈及己腈仅得到结构未定的混合产物.以1a为底物, 使用饱和的NHC配体S-IPr•HCl (L2)时结果更差(Entry 2).根据本课题组之前的研究, 氮杂环卡宾配体氮原子上取代基的空间位阻对这类反应的区域选择性(B/L)有很大的影响[4h], 尝试了氮上不同取代基的NHC为配体的反应.结果表明反应的选择性与配体的空间结构有关, 使用空间位阻较小的配体L3时, 几乎检测不到支链产物的生成(Entry 3).反之, 增大配体的空间位阻, 当使用空间位阻较大的配体L4时, 反应的选择性发生了改变, 支链产物3a变为了主产物, 收率为62%, B/L选择性为69/31 (Entry 4).使用手性NHC配体L5以及手性双膦配体(R)-Binap与手性膦氮配体(S)-iPr- Phox时, 产物3a的收率、区域、非对映选择性和对映选择性较差, ee值最高仅为20% (Entry 5)和30% (Entry 6), 如何发展高效的手性催化剂, 实现该反应的不对称催化依然是亟需克服的困难.

    表 1

    表 1  配体、钯源、温度和溶剂对反应的影响a
    Table 1.  Influence of ligand, Pd source, temperature and solvent on the reaction
    下载: 导出CSV
    Entry Ligand [Pd] T/℃ Solvent Yieldb/% of 3a n(B)/n(L)b drb of 3a
    1 L1 [Pd(η3-C3H5)Cl]2 25 THF 14 18/82 1.5:1
    2 L2 [Pd(η3-C3H5)Cl]2 25 THF 9 11/89 1:1
    3 L3 [Pd(η3-C3H5)Cl]2 25 THF 0 0/100
    4 L4 [Pd(η3-C3H5)Cl]2 25 THF 62 69/31 1.1:1
    5 L5 [Pd(η3-C3H5)Cl]2 25 THF 41 41/59 1:1
    6 (R)-Binap [Pd(η3-C3H5)Cl]2 25 THF 31 31/69 1.1:1
    7 (S)-iPr-Phox [Pd(η3-C3H5)Cl]2 25 THF 33 35/65 1.2:1
    8 L4 Pd(PPh3)4 25 THF 18 22/78 1:1
    9 L4 Pd(PPh3)2Cl2 25 THF 20 23/77 1:1
    10 L4 [Pd(π-cinnamyl)Cl]2 25 THF 57 59/41 1.1:1
    11 L4 [Pd(η3-C3H5)Cl]2 0 THF 59 59/41 1:1
    12 L4 [Pd(η3-C3H5)Cl]2 60 THF 45 55/45 1.1:1
    13 L4 [Pd(η3-C3H5)Cl]2 25 DME 62 70/30 1.2:1
    14 L4 [Pd(η3-C3H5)Cl]2 25 Dioxane 50 54/46 1:1
    15 L4 [Pd(η3-C3H5)Cl]2 25 Et2O 38 45/55 1:1
    16 L4 [Pd(η3-C3H5)Cl]2 25 Toluene 45 54/46 1.1:1
    17 L4 [Pd(η3-C3H5)Cl]2 25 DMSO 49 78/22 1.8:1
    a Reaction conditions: [Pd(η3-C3H5)Cl]2/L/1a/2a/LiHMDS=2.5/5/200/100/200;b Determined by 1H NMR.

    在此基础上, 对不同的钯源、温度和溶剂等条件进行了考察.只有使用[Pd(η3-C3H5)Cl]2 (Entry 4)和[Pd(π-cinnamyl)Cl]2 (Entry 10)为钯源时, 得到以支链为主的产物; 以Pd(PPh3)4或PdCl2(PPh3)2为钯源时, 均以直链产物为主, 这可能是由于PPh3的配位能力较强, 使得配体交换不充分导致结果较差(Entries 8和9).此外, 降低或者升高温度均会使反应的区域选择性降低(Entries 11和12).在对溶剂的考察中发现, 使用乙二醇二甲醚(DME)作溶剂时, 其反应结果与四氢呋喃作溶剂的结果几乎相当(Entries 4和13);而使用1, 4-二氧六环、乙醚和甲苯作溶剂时, 反应的区域选择性明显降低, B/L分别为54/46, 45/55和54/46 (Entries 14, 15和16);当使用极性非质子溶剂二甲基亚砜时, 反应体系较为复杂, 收率明显下降, 但是反应的选择性有所提升, 3a产率为49%, B/ L=78/22 (Entry 17).此外, 对反应所使用的碱、烯丙基试剂的离去基团以及众多添加剂进行考察, 均未取得更好的结果(见辅助材料).

    至此, 对上述反应的配体、钯源、温度、溶剂等一系列条件进行了考察, 但是结果并不令人满意.根据文献报道, 在钯催化烯丙基烷基化反应中, 存在着“记忆效应”, 即亲核试剂更倾向于进攻烯丙基试剂中离去基团所在的位点, 而这种效应在大位阻配体参与的反应中表现得更为明显[8].为此, 设想通过使用支链烯丙基试剂来提高反应的区域选择性.在[Pd(η3-C3H5)Cl]2为钯源, L4为配体, LiHMDS为碱, 不同溶剂条件下, 尝试使用支链烯丙基试剂5a进行该反应, 结果与设想相吻合, 反应的区域选择性有了大幅的提升(表 2).四氢呋喃为溶剂时支链产物3a的收率可以提高到87%, B/L值为89/11(表 2, Entry 1), 使用非极性溶剂正己烷时, 反应具有最优的效率, 能够以91%的收率, 96/4的区域选择性得到支链产物3(表 2, Entry 5), 降低或提高温度未能使反应效率提高(表 2, Entries 6和7).

    表 2

    表 2  使用支链烯丙基试剂条件下溶剂和温度对反应的影响a
    Table 2.  Influence of solvent and temperature on the reaction using branched allyl reagent
    下载: 导出CSV
    Entry Solvent T/℃ 3ab/% n(B)/n(L)b drb of 3a
    1 THF 25 87 89/11 1:1
    2 Dioxane 25 88 95/5 1.1:1
    3 DME 25 83 83/17 1:1
    4 Toluene 25 89 89/11 1.1:1
    5 Hexane 25 91 96/4 1.2:1
    6 Hexane 0 85 93/7 1.3:1
    7 Hexane 60 88 95/5 1.2:1
    a Reaction conditions: [Pd(η3-C3H5)Cl]2/L4/1a/5a/LiHMDS=2.5/5/200/100/ 200; b Determined by 1H NMR.

    底物适用范围考察结果见表 3. α-甲基苯乙腈作为亲核试剂时, 其支链产物3a的非对映选择性很差, dr值为1.2:1, 随着苄腈α-位取代基位阻的增大, 支链产物3a的非对映选择性随之提高.当α-位取代基为异丙基时, 反应的支链产物3d的非对映选择性显著提高到5.5:1;对于α-位为非烷基取代基叔丁基二甲基硅氧基(OTBS)时, 反应也具有非常高的区域选择性(B/L=98/2, 3e), 但dr值很差; 此外, 苄腈中苯基对位可以有不同的取代基, 如给电子取代基甲基(3f)和甲氧基(3g)、吸电子卤素氯(3h)或者溴(3i)等; 但是, 其邻位和间位取代基会影响反应的效率:当邻位存在取代基时, 反应几乎不能发生(3j3k); 间位取代基则会显著地抑制反应的进行, 当间位为甲氧基取代时, 反应只有33%的收率(3l), 这可能是受到空间位阻的影响; 另外, 对于α-位取代的杂芳基乙腈亲核试剂, 反应也可以顺利进行(3n3o), 收率和区域选择性良好, 非对映选择性差到中等(70%~74%, 73/27~90/10, dr=1.4:1~5:1).不同的烯丙基试剂的适用范围考察结果表明, 烯丙基试剂中芳基对位取代基对反应影响不大, 当对位为溴(3p)、酯基(3q)或者氯(3s)取代时, 反应都具有优秀的收率和区域选择性以及中等的非对映选择性(82%~88%, 90/10~95/5, dr=4.2:1~8.6:1);而对于间位取代的烯丙基试剂, 反应也可以顺利进行(3r3t); 与之前结果类似, 邻位取代基的存在会显著地抑制反应的进行(3u).值得一提的是, 对于吡啶取代的烯丙基试剂, 反应的非对映选择性可以提高到14.2:1 (3w).通过产物3d的X射线单晶衍射确定了上述反应中主产物的相对构型, 其氰基和烯丙基试剂中的苯基处于相对反式的位置.

    表 3

    表 3  反应的底物拓展a
    Table 3.  Substrate scope of the reaction
    下载: 导出CSV
    a Reaction conditions: [Pd(η3-C3H5)Cl]2/L4/1a/5a/LiHMDS=2.5/5/200/100/200; regio- and diastereo-selectivities were determined by 1H NMR; isolated yield; b relative configuration of 3d; c nd=not detected; d reaction temperature: 60 ℃; e [Pd(η3-C3H5)Cl]2: 5.0 mol%, L4: 10 mol%.

    为显示反应产物在合成中的应用价值, 对产物进行了转化(Scheme 3):产物3a可以被LiAlH4还原, 几乎定量地生成伯胺化合物6 (97%); 在低温下被DIBAL-H还原为醛类化合物7 (89%); 此外, 在甲基锂作用下, 该产物中的氰基并未与甲基锂发生加成反应生成相应的酮, 而是由于甲基锂的亲核性和强碱性导致该化合物发生了脱氰反应, 得到相应的烯烃化合物8 (91%).

    图式 3

    图式 3.  产物的衍生化
    Scheme 3.  Synthetic transformation of the products

    为了证明上述烯丙基烷基化反应中支链产物的生成是经历亲核试剂进攻π-烯丙基钯中间体的金属钯中心这一过程, 我们使用环状烯丙基试剂尝试了该反应(Scheme 4).所得产物10经NOESY谱图确认, 其反应位点的构型发生了翻转, 证明该反应中支链产物的生成是经历亲核试剂进攻π-烯丙基钯中间体的金属钯的过程[9].而该反应中直链产物很可能是通过亲核试剂直接进攻π-烯丙基钯中间体末端碳原子生成的.

    图式 4

    图式 4.  环状烯丙基试剂9的烯丙基烷基化反应
    Scheme 4.  Allylic alkylation reaction of allyl reagent 9

    利用NHC为配体, 实现了钯催化下α-取代芳腈与支链烯丙基试剂的烯丙基烷基化反应, 以中等到优良的区域选择性和收率获得了支链取代烯丙基化产物.配体氮上取代基对反应的区域选择性有至关重要的影响, 氮上大立体位阻基团的存在有利于支链产物的生成.芳腈α-位取代基的位阻大小则对该反应的非对映选择性有重要影响, 当α-位取代基为异丙基时, 可获得较好的非对映选择性.

    核磁共振氢谱和碳谱在Agilent 400 MHz和Varian Mercury 400 MHz型核磁共振仪上测定; 熔点由上海精科实业有限公司生产的WRS-2微机熔点仪测定; 质谱在Agilent Technologies 5973N或Shimadzu GCMS- QP2010型质谱仪上测定; 高分辨质谱在Thermo Fisher Scientific LTQ FT Ultra或Waters Micro mass GCT型仪器上测定; X-Ray单晶衍射使用RigakuAFC7R衍射仪在石墨单色Mo-Kα射线下搜集数据; 红外光谱在ShimadzuIR-400或Bio Rad FIS-185型红外光谱仪上测定; 过柱所用硅胶粒度为300~400目.除注明外, 所有反应均在氩气气氛下进行, 溶剂均根据《实验室化学品纯化手册》处理纯化.

    3.2.1   化合物3的合成及表征

    氩气保护下, 在10 mL Schlenk反应管中加入[Pd(η3-C3H5)Cl]2 (1.9 mg, 0.005 mmol)和L4 (9.5 mg, 0.01 mmol), 再加入正己烷(1.0 mL), 0 ℃下加入t-BuOK (25.0 μL, 1.0 mol•L-1四氢呋喃溶液, 0.025 mmol), 滴加完毕后于室温下反应30 min; 在另一25 mL Schlenk反应管中加入1 (0.4 mmol)和正己烷(1.0 mL), 0 ℃下加入LiHMDS (0.4 mL, 1.0 mol•L-1四氢呋喃溶液, 0.4 mmol), 滴加完毕后于室温下搅拌30 min.将催化剂加入到第二个反应管中, 再加入烯丙基试剂5 (0.2 mmol)和正己烷(1.0 mL)在25 ℃下进行反应.薄层色谱(TLC)跟踪反应至原料消失后, 加入0.2 mL去离子水淬灭, 过上层有无水硫酸钠的硅胶短柱, 乙酸乙酯淋洗, 减压除去溶剂, 粗产品经1H NMR确定支链直链比和非对映选择性, 经薄层层析分离确定收率[V(石油醚):V(乙酸乙酯)=20:1].

    2-甲基-2, 3-二苯基-4-戊烯腈(3a):无色液体. 1H NMR (400 MHz, CDCl3) (taken as a mixture of diasteromers) δ (major diastereomer): 7.45~6.93 (m, 10H), 6.39 (dt, J=16.8, 10.0 Hz, 1H), 5.34~5.27 (m, 2H), 3.52 (d, J=9.6 Hz, 1H), 1.84 (s, 3H); δ(minor diastereomer): 6.12 (ddd, J=16.8, 10.0, 8.8 Hz, 1H), 5.07 (ddd, J=10.2, 1.2, 0.8 Hz, 1H), 4.86 (dt, J=16.8, 1.2 Hz, 1H), 3.62 (d, J=8.8 Hz, 1H), 1.58 (s, 3H); 13C NMR (101 MHz, CDCl3) (taken as a mixture of diasteromers) δ: 139.1, 138.7, 138.6, 138.4, 136.1, 135.5, 129.1, 128.6 (2C), 128.5, 128.3, 128.0, 127.9, 127.7 (2C), 127.2, 126.5, 126.4, 122.5 (2C), 119.2, 119.1, 60.8, 59.9, 47.2, 47.0, 26.1, 25.7; IR (Neat) v: 3087, 3063, 3029, 2987, 2235, 1601, 1493, 1378, 931, 760, 696 cm-1; MS (EI) m/z: 247 (M+, 1), 151 (8), 117 (100), 115 (30), 91 (9), 77 (3), 65 (2); HRMS (EI) calcd for C18H17N: 247.1361, found 247.1359.

    2-乙基-2, 3-二苯基-4-戊烯腈(3b):淡黄色液体.1H NMR (400 MHz, CDCl3) (taken as a mixture of diasteromers) δ(major diastereomer): 7.43~6.94 (m, 10H), 6.08 (ddd, J=16.8, 10.0, 8.8 Hz, 1H), 5.00 (d, J=10.0 Hz, 1H), 4.80 (d, J=16.8 Hz, 1H), 3.66 (d, J=8.8 Hz, 1H), 1.99~1.90 (m, 1H), 1.81~1.72 (m, 1H), 0.77 (t, J=7.6 Hz, 3H); δ (minor diastereomer): 6.41 (dt, J=16.4, 10.0 Hz, 1H), 5.33~5.27 (m, 2H), 3.57 (d, J=10.0 Hz, 1H), 2.39~2.30 (m, 1H), 2.07~1.99 (m, 1H), 0.89 (t, J=7.6 Hz, 3H); 13C NMR (101 MHz, CDCl3) (taken as a mixture of diasteromers) δ: 139.0, 138.9, 136.8, 136.6, 136.0, 135.7, 129.2, 128.6 (2C), 128.5, 128.3, 128.0, 127.8, 127.7, 127.5, 127.1, 127.0 (2C), 121.4 (2C), 119.0, 118.7, 60.5, 59.7, 53.8, 53.6, 31.7, 31.2, 9.7, 9.6; IR (Neat) v: 3084, 3063, 3031, 2975, 2937, 2234, 1601, 1493, 1450, 991, 924, 755, 720, 697 cm-1; MS (EI) m/z: 261 (M+, 1), 144 (10), 117 (100), 116 (13), 91 (10), 77 (2), 51 (2); HRMS (EI) calcd for C19H19N: 261.1517, found 261.1525.

    2-新戊基-2, 3-二苯基-4-戊烯腈(3c):白色固体. m.p. 64.8~65.6 ℃; 1H NMR (400 MHz, CDCl3) (taken as a mixture of diasteromers) δ (major diastereomer): 7.49~6.89 (m, 10 H), 5.96 (ddd, J=16.8, 10.0, 8.8 Hz, 1H), 4.86 (d, J=10.0 Hz, 1H), 4.63 (d, J=16.8 Hz, 1H), 3.59 (d, J=8.8 Hz, 1H), 1.89 (d, J=14.4 Hz, 1H), 1.65 (d, J=14.4 Hz, 1H), 0.63 (s, 9H); δ(minor diastereomer) 6.44 (dt, J=16.8, 10.0 Hz, 1H), 5.28 (dd, J=10.0, 1.2 Hz, 1H), 5.23 (d, J=16.8 Hz, 1H), 3.48 (d, J=9.6 Hz, 1H), 2.31 (d, J=14.8 Hz, 1H), 2.01 (d, J=14.8 Hz, 1H), 0.77 (s, 9H); 13C NMR (101 MHz, CDCl3) (taken as a mixture of diasteromers) δ:139.0, 138.7, 137.8, 137.0 (2C), 135.5, 129.4, 128.7, 128.5, 128.4, 128.1, 127.8, 127.7 (2C), 127.3, 127.2, 126.8, 122.1, 122.0, 119.2, 118.7, 62.2, 62.0, 50.3, 50.1, 49.9, 49.8, 31.9, 31.8, 31.2, 30.9; IR (Neat) v: 3063, 2955, 2237, 1601, 1493, 1476, 1368, 1033, 995, 927, 787, 717, 698 cm-1; MS (EI) m/z: 303 (M+, 1), 205 (2), 159 (4), 117 (100), 115 (19), 91 (6), 77 (2), 57 (4); HRMS (EI) calcd for C22H25N: 303.1987, found 303.1992.

    2-异丙基-2, 3-二苯基-4-戊烯腈(3d):白色固体. m.p. 58.9~60.0 ℃; 1H NMR (400 MHz, CDCl3) (taken as a mixture of diasteromers) δ (major diastereomer): 7.27~6.85 (m, 10H), 6.00 (dt, J=16.8, 9.6 Hz, 1H), 5.16~5.11 (m, 2H), 4.01 (d, J=9.2 Hz, 1H), 2.44~2.38 (m, 1H), 1.18 (d, J=6.4 Hz, 3H), 0.83 (d, J=6.8 Hz, 3H); δ (minor diastereomer): 6.15 (dt, J=16.8, 10.0 Hz, 1H), 5.28 (d, J=16.8 Hz, 1H), 5.22 (d, J=10.0 Hz, 1H), 4.05 (d, J=9.6 Hz, 1H), 2.39~2.34 (m, 1H), 1.16 (d, J=6.4 Hz, 3H), 0.87 (d, J=6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) (taken as a mixture of diasteromers) δ: 133.4, 133.2, 131.6, 129.6, 128.9, 128.1, 124.0, 123.9, 123.5, 123.3, 122.6, 122.5, 122.3 (2C), 122.0, 121.7, 116.3, 115.6, 113.5, 113.0, 52.7, 51.9, 49.2, 48.7, 28.0, 27.1, 13.9, 13.4, 12.9, 12.5; IR (Neat) v: 3064, 3031, 2969, 2235, 1601, 1495, 1469, 1447, 1032, 992, 925, 753, 696 cm-1; MS (EI) m/z: 275 (M+, 1), 171 (4), 156 (5), 117 (100), 115 (25), 104 (9), 91 (11), 77 (2), 51 (1); HRMS (EI) calcd for C20H21N: 275.1674, found 275.1676.

    2-叔丁基二甲基硅氧基-2, 3-二苯基-4-戊烯腈(3e):无色液体.1H NMR (400 MHz, CDCl3) (taken as a mixture of diasteromers) δ(major diastereomer): 7.44~7.04 (m, 10H), 6.22 (ddd, J=17.2, 10.4, 9.2 Hz, 1H), 5.14 (d, J=10.4 Hz, 1H), 4.95 (d, J=17.2 Hz, 1H), 3.70 (d, J=9.2 Hz, 1H), 0.84 (s, 9H), -0.03 (s, 3H), -0.16 (s, 3H); δ (minor diastereomer): 6.38 (ddd, J=16.8, 10.4, 8.8 Hz, 1H), 5.27 (d, J=10.4 Hz, 1H), 5.13 (d, J=16.8 Hz, 1H), 3.72 (d, J=8.8 Hz, 1H), 0.98 (s, 9H), 0.13 (s, 3H), -0.13 (s, 3H); 13C NMR (101 MHz, CDCl3) (taken as a mixture of diasteromers) δ: 139.6, 139.2, 137.7, 137.4, 135.0, 134.5, 129.9, 129.5, 128.7, 128.6, 128.0, 127.9 (2C), 127.4, 127.3, 126.1, 126.0, 120.0 (2C), 119.7, 119.6, 78.9 (2C), 63.5 (2C), 25.9, 25.7, 18.5, 18.4, -3.7, -3.8, -4.1, -4.4; IR (Neat) v: 3087, 3032, 2957, 2930, 2858, 2233, 1602, 1493, 1256, 1099, 1075, 934, 881, 835, 780, 696 cm-1; MS (EI) m/z: 363 (M+, 0.04), 306 (10), 279 (6), 246 (62), 175 (43), 117 (13), 105 (100), 91 (5), 73 (15), 59 (3); HRMS (EI) calcd for C23H29NOSi: 363.2018, found 363.2025.

    2-异丙基-3-苯基-2-对甲苯基-4-戊烯腈(3f):无色液体.1H NMR (400 MHz, CDCl3) (taken as a mixture of diasteromers) δ(major diastereomer): 7.22~6.94 (m, 9H), 6.04 (dt, J=16.8, 9.6 Hz, 1H), 5.18 (d, J=9.6 Hz, 1H), 5.16 (d, J=16.8 Hz, 1H), 4.05 (d, J=9.2 Hz, 1H), 2.46~2.33 (m, 1H), 2.36 (s, 3H), 1.20 (d, J=6.8 Hz, 3H), 0.87 (d, J=6.8 Hz, 3H); δ (minor diastereomer): 6.18 (dt, J=17.2, 9.6 Hz, 1H), 5.32 (d, J=17.2 Hz, 1H), 5.26 (d, J=9.6 Hz, 1H), 4.08 (d, J=9.2 Hz, 1H), 2.46~2.33 (m, 1H), 2.30 (s, 3H), 1.20 (d, J=6.8 Hz, 3H), 0.90 (d, J=6.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) (taken as a mixture of diasteromers) δ:138.9, 138.7, 137.5, 137.3, 137.1, 135.3, 131.1, 130.3, 129.4 (2C), 128.8, 128.6, 128.5, 128.3, 127.9 (2C), 127.3, 127.0, 121.8, 121.2, 118.7, 118.2, 57.6, 56.9, 54.4, 53.9, 33.3, 32.5, 21.0, 20.9, 19.2, 18.6, 18.3, 17.8; IR (Neat) v: 3062, 3030, 2969, 2877, 2233, 1737, 1513, 1452, 1390, 967, 922, 803, 728, 701, 526, 476 cm-1; MS (EI) m/z: 289 (M+, 1), 246 (1), 117 (100), 91 (14), 77 (3), 51 (2); HRMS (EI) calcd for C21H23N: 289.1830, found 289.1835.

    2-异丙基-2-对甲氧基苯基-3-苯基-4-戊烯腈(3g):无色液体. 1H NMR (400 MHz, CDCl3) (taken as a mixture of diasteromers) δ (major diastereomer): 7.20~6.74 (m, 9H), 6.02 (dt, J=16.8, 10.0 Hz, 1H), 5.17 (d, J=10.0 Hz, 1H), 5.15 (d, J=16.8 Hz, 1H), 4.01 (d, J=9.2 Hz, 1H), 3.80 (s, 3H), 2.44~2.34 (m, 1H), 1.20 (d, J=6.4 Hz, 3H), 0.86 (d, J=6.8 Hz, 3H); δ (minor diastereomer): 6.16 (dt, J=16.8, 10.0 Hz, 1H), 5.30 (d, J=16.8 Hz, 1H), 5.25 (d, J=10.0 Hz, 1H), 4.03 (d, J=10.0 Hz, 1H), 3.76 (s, 3H), 2.37~2.27 (m, 1H), 1.19 (d, J=6.0 Hz, 3H), 0.88 (d, J=6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) (taken as a mixture of diasteromers) δ:159.0, 158.8, 139.0, 138.6, 137.1, 135.1, 130.0, 129.7, 129.5, 129.4, 127.9, 127.3, 127.0, 126.1, 125.4, 121.8, 121.2, 118.7, 118.3, 113.2, 112.9, 57.3, 56.6, 55.2 (2C), 54.5, 54.0, 33.3, 32.5, 19.2, 18.7, 18.3, 17.9; IR (Neat) v: 3062, 3032, 2967, 2934, 2233, 1736, 1609, 1512, 1465, 1296, 1252, 1186, 1033, 922, 836, 734, 701, 668 cm-1; MS (EI) m/z: 305 (M+, 3), 188 (100), 146 (7), 117 (30), 91 (5), 77 (2), 57 (4); HRMS (EI) calcd for C21H23NO: 305.1780, found 305.1776.

    2-对氯苯基-2-异丙基-3-苯基-4-戊烯腈(3h):无色液体. 1H NMR (400 MHz, CDCl3) (taken as a mixture of diasteromers) δ (major diastereomer): 7.29~6.90 (m, 9H), 5.98 (dt, J=16.8, 10.0 Hz, 1H), 5.20 (d, J=10.0 Hz, 1H), 5.18 (d, J=16.8 Hz, 1H), 4.02 (d, J=9.6 Hz, 1H), 2.45~2.36 (m, 1H), 1.21 (d, J=6.4 Hz, 3H), 0.85 (d, J=6.8 Hz, 3H); δ (minor diastereomer): 6.15 (dt, J=16.4, 10.0 Hz, 1H), 5.31 (d, J=16.8 Hz, 1H), 5.27 (d, J=9.2 Hz, 1H), 4.05 (d, J=9.2 Hz, 1H), 2.39~2.32 (m, 1H), 1.19 (d, J=6.8 Hz, 3H), 0.88 (d, J=6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) (taken as a mixture of diasteromers) δ:138.4, 138.2, 136.6, 134.5, 133.9, 133.7, 132.9, 132.2, 130.2, 130.0, 129.3, 129.2, 128.8, 128.1 (2C), 127.8, 127.5, 127.3, 121.3, 120.6, 119.2, 118.7, 57.7, 56.9, 54.4, 53.9, 33.4, 32.5, 19.2, 18.7, 18.3, 17.8; IR (Neat) v: 3065, 3032, 2970, 2934, 2878, 2234, 1493, 1392, 1096, 1013, 923, 813, 735, 700, 525, 475 cm-1; MS (EI) m/z: 309 (M+, 0.1), 230 (1), 177 (2), 117 (100), 91 (13), 77 (2), 51 (2); HRMS (EI) calcd for C20H20ClN: 309.1284, found 309.1286.

    2-对溴苯基-2-异丙基-3-苯基-4-戊烯腈(3i):无色液体. 1H NMR (400 MHz, CDCl3) δ (major diastereomer): 7.43 (d, J=8.0 Hz, 2H), 7.21~7.20 (m, 3H), 7.06 (d, J=8.0 Hz, 2H), 6.92~6.90 (m, 2H), 5.97 (dt, J=16.8, 10.0 Hz, 1H), 5.20 (d, J=10.0 Hz, 1H), 5.17 (d, J=16.8 Hz, 1H), 4.01 (d, J=9.6 Hz, 1H), 2.43~2.36 (m, 1H), 1.20 (d, J=6.8 Hz, 3H), 0.85 (d, J=6.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ (major diastereomer): 138.4, 134.5, 133.5, 131.1, 130.3, 129.4, 128.1, 127.6, 122.1, 120.6, 119.3, 57.8, 54.3, 32.5, 18.7, 18.3; IR (Neat) v: 3065, 3033, 2919, 2850, 2339, 1491, 1393, 1261, 1079, 1011, 803, 732, 701, 524, 507 cm-1; MS (EI) m/z: 353 (M+, 0.2), 191 (3), 117 (100), 91 (11), 77 (3), 65 (2), 51 (2); HRMS (EI) calcd for C20H20BrN: 353.0779, found 353.0783.

    2-异丙基-2-间甲氧基苯基-3-苯基-4-戊烯腈(3l):无色液体. 1H NMR (400 MHz, CDCl3) δ (major diastereomer): 7.25~7.17 (m, 4H), 6.93~6.91 (m, 2H), 6.85 (dd, J=8.4, 2.4 Hz, 1H), 6.82 (d, J=8.4 Hz, 1H), 6.70 (s, 1H), 6.08 (dt, J=17.2, 9.6 Hz, 1H), 5.20 (d, J=10.0 Hz, 1H), 5.18 (d, J=17.2 Hz, 1H), 4.03 (d, J=9.6 Hz, 1H), 3.72 (s, 3H), 2.47~2.40 (m, 1H), 1.23 (d, J=6.4 Hz, 3H), 0.90 (d, J=6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ (major diastereomer): 159.1, 142.5, 138.8, 135.8, 134.9, 129.4, 128.8, 127.9, 127.3, 120.9, 118.8, 114.9, 113.1, 58.1, 55.2, 54.6, 32.5, 18.8, 18.2; IR (Neat) v: 3081, 2966, 2932, 2233, 1601, 1583, 1491, 1432, 1294, 1247, 1051, 925, 781, 720, 700, 570, 516, 462 cm-1; MS (EI) m/z: 305 (M+, 1), 202 (1), 173 (3), 117 (100), 91 (13), 77 (3), 51 (2); HRMS (EI) calcd for C21H23NO: 305.1780, found 305.1775.

    2-异丙基-2-(2-萘基)-3-苯基-4-戊烯腈(3m):无色液体. 1H NMR (400 MHz, CDCl3) δ (taken as a mixture of diasteromers): δ (major diastereomer): 7.85~6.91 (m, 12H), 6.07 (dt, J=17.2, 9.6 Hz, 1H), 5.19 (d, J=17.2 Hz, 1H), 5.18 (d, J=9.6 Hz, 1H), 4.15 (d, J=9.2 Hz, 1H), 2.60~2.53 (m, 1H), 1.25 (d, J=6.4 Hz, 3H), 0.90 (d, J=6.4 Hz, 3H); δ (minor diastereomer): 6.20 (dt, J=16.8, 10.0 Hz, 1H), 5.36 (d, J=16.8 Hz, 1H), 5.28 (d, J=9.2 Hz, 1H), 4.19 (d, J=10.0 Hz, 1H), 2.51~2.45 (m, 1H), 1.25 (d, J=6.4 Hz, 3H), 0.92 (d, J=6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) (taken as a mixture of diasteromers) δ:138.7, 138.5, 136.9, 135.1, 132.6 (2C), 132.5 (2C), 131.7, 131.1, 129.4 (2C), 128.6, 128.3, 128.2, 128.0, 127.5, 127.4 (2C), 127.3, 127.1, 127.0, 126.5, 126.4, 126.3, 126.1, 125.5, 121.7, 121.1, 118.9, 118.5, 58.2, 57.6, 54.7, 54.0, 33.4, 32.6, 19.3, 18.9, 18.4, 18.2; IR (Neat) v:3060, 2962, 2921, 2851, 2233, 1736, 1598, 1453, 1372, 1241, 999, 922, 814, 746, 701, 510, 478 cm-1; MS (EI) m/z: 325 (M+, 3), 208 (7), 193 (7), 128 (8), 165 (10), 117 (100), 91 (11), 65 (2); HRMS (EI) calcd for C24H23N: 325.1830, found 325.1827.

    2-异丙基-3-苯基-2-(2-吡啶基)-4-戊烯腈(3n):无色液体. 1H NMR (400 MHz, CDCl3) δ (taken as a mixture of diasteromers): δ (major diastereomer): 8.57 (d, J=4.0 Hz, 1H), 7.46 (td, J=8.0, 2.0 Hz, 1H), 7.28~7.00 (m, 7H), 6.46 (dt, J=17.2, 10.0 Hz, 1H), 5.35 (d, J=17.2 Hz, 1H), 5.30 (d, J=10.4 Hz, 1H), 4.47 (d, J=10.0 Hz, 1H), 2.63~2.56 (m, 1H), 1.06 (d, J=6.8 Hz, 3H), 1.05 (d, J=6.8 Hz, 3H); δ (minor diastereomer): 8.67 (d, J=3.6 Hz, 1H), 7.53 (td, J=7.6, 1.6 Hz, 1H), 5.12 (d, J=10.4 Hz, 1H), 5.08 (d, J=17.2 Hz, 1H), 4.28 (d, J=9.2 Hz, 1H), 2.71~2.64 (m, 1H), 1.15 (d, J=6.8 Hz, 3H), 0.80 (d, J=6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) (taken as a mixture of diasteromers) δ:155.3, 154.7, 148.7, 148.5, 140.1, 139.5, 136.9, 136.0 (2C), 135.8, 129.0, 128.9, 128.1, 127.8, 127.2, 126.7, 124.5, 123.8, 122.5, 122.3, 121.8, 121.3, 118.3, 118.1, 59.1, 58.3, 54.7, 53.7, 35.3, 33.0, 19.7, 18.7, 18.1, 17.3; IR (Neat) v: 3062, 2969, 2934, 2234, 1587, 1467, 1431, 994, 922, 773, 748, 722, 699, 526 cm-1; MS (EI) m/z: 276 (M+, 5), 261 (12), 233 (92), 117 (100), 91 (25), 78 (12), 65 (5), 51 (8); HRMS (EI) calcd for C19H20N2: 276.1626, found 276.1633.

    2-异丙基-3-苯基-2-(2-噻吩基)-4-戊烯腈(3o):无色液体. 1H NMR (400 MHz, CDCl3) δ (taken as a mixture of diasteromers): δ (major diastereomer): 7.29~6.81 (m, 8H), 6.26 (dt, J=16.8, 10.0 Hz, 1H), 5.21 (d, J=10.4 Hz, 1H), 5.16 (d, J=16.8 Hz, 1H), 3.95 (d, J=9.2 Hz, 1H), 2.26~2.16 (m, 1H), 1.17 (d, J=6.4 Hz, 3H), 0.95 (d, J=6.4 Hz, 3H); δ (minor diastereomer): 6.36 (dt, J=17.2, 10.0 Hz, 1H), 5.30 (d, J=17.2 Hz, 1H), 5.28 (d, J=10.0 Hz, 1H), 3.90 (d, J=9.6 Hz, 1H), 2.45~2.38 (m, 1H), 1.13 (d, J=6.8 Hz, 3H), 1.12 (d, J=6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) (taken as a mixture of diasteromers) δ:138.9 (2C), 138.4, 136.5, 134.9, 129.1, 128.9, 128.6, 128.5, 128.2, 128.1, 128.0, 127.5, 127.1, 126.2, 126.0, 125.3, 125.0, 121.3, 120.5, 119.3, 118.6, 56.0, 55.7, 55.4, 34.9, 34.8, 19.4, 18.6, 18.3, 17.0; IR (Neat) v: 3080, 2969, 2877, 2235, 1637, 1584, 1493, 1390, 1239, 924, 697, 517 cm-1; MS (EI) m/z: 281 (M+, 1), 164 (8), 149 (4), 117 (100), 91 (15), 65 (3), 51 (2); HRMS (EI) calcd for C18H19NS: 281.1238, found 281.1245.

    3-对溴苯基-2-异丙基-2-苯基-4-戊烯腈(3p):无色液体. 1H NMR (400 MHz, CDCl3) δ (major diastereomer): 7.31~7.28 (m, 5H), 7.17~7.16 (m, 2H), 6.71 (d, J=8.4 Hz, 2H), 5.97 (dt, J=16.8, 10.0 Hz, 1H), 5.21 (d, J=9.2 Hz, 1H), 5.18 (d, J=16.8 Hz, 1H), 4.00 (d, J=9.6 Hz, 1H), 2.50~2.40 (m, 1H), 1.23 (d, J=6.4 Hz, 3H), 0.85 (d, J=6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ (major diastereomer): 137.8, 134.2, 133.9, 131.1, 131.0, 128.5, 128.1, 128.0, 121.5, 120.7, 119.3, 58.0, 54.0, 32.4, 18.8, 18.2; IR (Neat) v: 3084, 3056, 2983, 2962, 2925, 2232, 1588, 1488, 1469, 1077, 1008, 928, 816, 733, 702, 643, 578, 510 cm-1; MS (EI) m/z: 353 (M+, 0.2), 195 (34), 116 (100), 89 (7), 77 (4), 63 (3), 51 (3); HRMS (EI) calcd for C20H20BrN: 353.0779, found 353.0781.

    4-(4-氰基-5-甲基-4-苯基-3-(1-己烯基)-苯甲酸甲酯(3q):无色液体. 1H NMR (400 MHz, CDCl3) δ (major diastereomer): 7.83 (d, J=8.4 Hz, 2H), 7.30~7.26 (m, 3H), 7.16~7.14 (m, 2H), 6.91 (d, J=8.4 Hz, 2H), 6.03 (dt, J=16.8, 10.0 Hz, 1H), 5.23 (d, J=9.2 Hz, 1H), 5.20 (d, J=16.0 Hz, 1H), 4.09 (d, J=9.6 Hz, 1H), 3.87 (s, 3H), 2.52~2.42 (m, 1H), 1.24 (d, J=6.8 Hz, 3H), 0.86 (d, J=6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ (major diastereomer): 166.8, 144.0, 134.0, 133.9, 129.5, 129.1 (2C), 128.5, 128.1 (2C), 120.6, 119.6, 57.9, 54.6, 52.1, 32.4, 18.9, 18.2; IR (Neat) v: 3061, 2983, 2947, 2874, 2232, 1719, 1608, 1435, 1278, 1181, 1112, 1009, 922, 723, 702, 644, 515 cm-1; MS (EI) m/z: 333 (M+, 1), 302 (3), 203 (4), 175 (100), 143 (24), 131 (40), 115 (83), 91 (32), 77 (7), 59 (19); HRMS (EI) calcd for C22H23NO2: 333.1729, found 333.1736.

    2-异丙基-3-对甲氧基苯基-2-苯基-4-戊烯腈(3r):无色液体. 1H NMR (400 MHz, CDCl3) δ (taken as a mixture of diasteromers): δ (major diastereomer): 7.33~7.22 (m, 5H), 7.13 (t, J=8.0 Hz, 1H), 6.77 (ddd, J=8.4, 2.8, 0.8 Hz, 1H), 6.60 (d, J=7.6 Hz, 1H), 6.39 (t, J=2.0 Hz, 1H), 6.04 (ddd, J=16.8, 10.4, 9.6 Hz, 1H), 5.20 (d, J=9.2 Hz, 1H), 5.19 (d, J=16.8 Hz, 1H), 4.04 (d, J=9.2 Hz, 1H), 3.65 (s, 3H), 2.51~2.40 (m, 1H), 1.22 (d, J=6.8 Hz, 3H), 0.88 (d, J=6.4 Hz, 3H); δ (minor diastereomer) 7.06 (t, J=8.0 Hz, 1H), 6.67 (dd, J=8.4, 2.4 Hz, 1H), 6.65 (d, J=8.4 Hz, 1H), 6.52 (t, J=2.0 Hz, 1H), 6.18 (dt, J=16.8, 9.6 Hz, 1H), 5.33 (d, J=16.8 Hz, 1H), 5.28 (dd, J=10.0, 1.2 Hz, 1H), 4.07 (d, J=9.6 Hz, 1H), 3.65 (s, 3H), 2.46~2.39 (m, 1H), 1.21 (d, J=6.8 Hz, 3H), 0.92 (d, J=6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) (taken as a mixture of diasteromers) δ:159.0 (2C), 140.3, 140.1, 136.9, 134.9, 134.4, 133.5, 128.9 (2C), 128.6, 128.0, 127.9, 127.7, 127.6, 121.9, 121.7 (2C), 121.0, 118.9, 118.4, 114.9, 114.5 (2C), 113.4, 112.7, 58.0, 57.3, 55.1, 55.0, 54.6, 54.0, 33.4, 32.5, 19.3, 18.8, 18.3, 17.9; IR (Neat) v: 3060, 2967, 2835, 2233, 1736, 1599, 1492, 1265, 1042, 924, 726, 698, 522 cm-1; MS (EI) m/z: 305 (M+, 1), 147 (100), 131 (6), 115 (16), 91 (17), 77 (5); HRMS (EI) calcd for C21H23NO: 305.1780, found 305.1788.

    3-对氯苯基-2-异丙基-2-苯基-4-戊烯腈(3s):无色液体. 1H NMR (400 MHz, CDCl3) δ (major diastereomer): 7.33~7.30 (m, 3H), 7.22~7.14 (m, 4H), 6.79~6.77 (m, 2H), 6.00 (dt, J=16.8, 9.6 Hz, 1H), 5.23 (d, J=9.2 Hz, 1H), 5.20 (d, J=16.8 Hz, 1H), 4.03 (d, J=9.6 Hz, 1H), 2.53~2.43 (m, 1H), 1.25 (d, J=6.8 Hz, 3H), 0.87 (d, J=6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ (major diastereomer): 137.3, 134.3 (2C), 133.9, 133.3, 130.7, 128.6, 128.1 (2C), 120.7, 119.3, 58.1, 54.0, 32.4, 18.9, 18.2; IR (Neat) v: 3062, 2969, 2878, 2233, 1736, 1492, 1448, 1092, 1013, 925, 820, 733, 702, 647, 512 cm-1; MS (EI) m/z: 309 (M+, 1), 230 (1), 151 (100), 115 (58), 89 (7), 77 (4), 51 (3); HRMS (EI) calcd for C20H20ClN: 309.1284, found 309.1294.

    3-间氯苯基-2-异丙基-2-苯基-4-戊烯腈(3t):无色液体. 1H NMR (400 MHz, CDCl3) δ (taken as a mixture of diasteromers): δ (major diastereomer): 7.34~6.69 (m, 9H), 5.99 (dt, J=16.8, 9.6 Hz, 1H), 5.23 (d, J=9.2 Hz, 1H), 5.20 (d, J=16.4 Hz, 1H), 4.02 (d, J=9.2 Hz, 1H), 2.54~2.44 (m, 1H), 1.25 (d, J=6.4 Hz, 3H), 0.89 (d, J=6.8 Hz, 3H); δ (minor diastereomer): 6.17 (dt, J=16.8, 9.6 Hz, 1H), 5.33 (d, J=16.0 Hz, 1H), 5.30 (d, J=9.6 Hz, 1H), 4.06 (d, J=9.6 Hz, 1H), 2.44~2.34 (m, 1H), 1.18 (d, J=6.4 Hz, 3H), 0.92 (d, J=6.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) (taken as a mixture of diasteromers) δ:140.7 (2C), 136.3, 134.1, 133.9, 133.7, 133.6, 133.1, 129.5 (2C), 129.1 (2C), 128.7, 128.5, 128.1, 128.0, 127.9, 127.8, 127.7, 127.5, 127.2 (2C), 121.3, 120.6, 119.4, 119.0, 58.0, 57.1, 54.3, 53.7, 33.5, 32.3, 19.3, 18.9, 18.1, 17.8; IR (Neat) v: 3062, 2970, 2935, 2233, 1595, 1572, 1474, 1092, 999, 926, 792, 727, 700, 519, 444 cm-1; MS (EI) m/z: 309 (M+, 2), 203 (3), 151 (100), 115 (62), 91 (9), 77 (5), 63 (3), 51 (4); HRMS (EI) calcd for C20H20ClN: 309.1284, found 309.1287.

    3-邻氯苯基-2-异丙基-2-苯基-4-戊烯腈(3u):无色液体. 1H NMR (400 MHz, CDCl3) δ (major diastereomer): 7.43 (dd, J=8.4, 1.6 Hz, 1H), 7.40~7.34 (m, 5H), 7.17 (td, J=7.6, 1.6 Hz, 1H), 7.04 (td, J=7.6, 1.2 Hz, 1H), 6.70 (dd, J=8.0, 1.6 Hz, 1H), 5.87 (ddd, J=17.2, 10.4, 9.2 Hz, 1H), 5.15 (d, J=10.4 Hz, 1H), 5.12 (d, J=17.2 Hz, 1H), 4.96 (d, J=8.8 Hz, 1H), 2.53~2.43 (m, 1H), 1.21 (d, J=6.4 Hz, 3H), 0.82 (d, J=6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ (major diastereomer): 136.4, 135.1, 134.7, 134.6, 130.1, 129.9, 128.7, 128.4, 128.1, 128.0, 126.3, 120.6, 119.1, 57.2, 48.7, 33.2, 18.7 (2C); IR (Neat) v: 3063, 2967, 2877, 2235, 1744, 1494, 1471, 1446, 1259, 1034, 925, 799, 739, 703, 653, 517, 460 cm-1; MS (EI) m/z: 309 (M+, 1), 266 (2), 195 (5), 151 (100), 115 (70), 91 (12), 77 (8), 63 (6), 51(5); HRMS (EI) calcd for C20H20ClN: 309.1284, found 309.1288.

    2-异丙基-3-(2-萘基)-2-苯基-4-戊烯腈(3v):无色液体. 1H NMR (400 MHz, CDCl3) δ (taken as a mixture of diasteromers): δ (major diastereomer): 8.04~7.48 (m, 11H), 7.24 (d, J=8.8 Hz, 1H), 6.41 (dt, J=16.4, 10.4 Hz, 1H), 5.48 (d, J=10.0 Hz, 1H), 5.47 (d, J=16.4 Hz, 1H), 4.51 (d, J=9.6 Hz, 1H), 2.82~2.71 (m, 1H), 1.52 (d, J=6.4 Hz, 3H), 1.17 (d, J=6.8 Hz, 3H); δ (minor diastereomer): 7.37 (d, J=8.4 Hz, 1H), 6.54 (dt, J=17.2, 9.2 Hz, 1H), 5.62 (d, J=16.8 Hz, 1H), 5.56 (d, J=10.8 Hz, 1H), 4.53 (d, J=10.8 Hz, 1H), 2.73~2.66 (m, 1H), 1.52 (d, J=6.4 Hz, 3H), 1.19 (d, J=6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) (taken as a mixture of diasteromers) δ:136.9, 136.3, 136.0, 135.0, 134.9, 134.2, 133.9, 133.4, 133.0, 132.9, 132.6, 132.3, 130.5, 128.9, 128.7, 128.5, 128.0 (2C), 127.9, 127.8 (2C), 127.7, 127.4 (2C), 127.3, 127.2, 125.9 (3C), 121.7, 121.0, 119.0, 118.6, 58.1, 57.4, 54.7, 54.1, 33.3, 32.5, 19.3, 18.8, 18.3, 17.9; IR (Neat) v: 3058, 2968, 2935, 2233, 1633, 1599, 1447, 1262, 909, 818, 724, 700, 478 cm-1; MS (EI) m/z: 325 (M+, 1), 167 (100), 152 (20), 115 (6), 91 (3), 77 (2), 63 (1); HRMS (EI) calcd for C24H23N: 325.1830, found 325.1832.

    2-异丙基-2-苯基-3-(3-吡啶基)-4-戊烯腈(3w):无色液体. 1H NMR (400 MHz, CDCl3) δ (major diastereomer): 8.61 (d, J=4.4 Hz, 1H), 8.22 (s, 1H), 7.49~7.48 (m, 3H), 7.35~7.26 (m, 4H), 6.20 (dt, J=16.8, 10.0 Hz, 1H), 5.42 (d, J=10.0 Hz, 1H), 5.39 (d, J=16.8 Hz, 1H), 4.23 (d, J=9.2 Hz, 1H), 2.70~2.60 (m, 1H), 1.43 (d, J=6.8 Hz, 3H), 1.05 (d, J=6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ (major diastereomer): 150.7, 148.9, 136.9, 134.6, 133.8 (2C), 128.6, 128.4 (2C), 122.9, 120.6, 120.0, 58.2, 52.5, 32.5, 19.0, 18.3; IR (Neat) v: 3034, 2969, 2934, 2234, 1735, 1575, 1427, 1260, 1025, 927, 807, 724, 702, 525 cm-1; MS (EI) m/z: 276 (M+, 1), 151 (6), 118 (100), 91 (19), 77 (4), 65 (6), 51 (4); HRMS (EI) calcd for C19H20N2: 276.1626, found 276.1634.

    3.2.2   2-甲基-2, 3-二苯基-4-戊烯胺(6)的合成

    氩气保护下, 在10 mL封管中加入LiAlH4 (12.2 mg, 0.32 mmol)和乙醚(0.5 mL), 0 ℃下加入3a (40.0 mg, 0.16 mmol).滴加完毕后恢复室温反应过夜.加入10% NaOH水溶液小心淬灭至无气泡产生, 乙酸乙酯萃取(10 mL×3).合并有机相, 滴加1 mol•L-1盐酸溶液至pH=1, 分离水相, 有机相用去离子水萃取(10 mL×3), 合并水相, 用10% NaOH溶液中和至体系呈碱性后, 乙酸乙酯萃取(10 mL×3), 无水硫酸钠干燥, 过滤, 减压除去溶剂得到无色液体6 38.9 mg, 产率97%. 1H NMR (400 MHz, CDCl3) δ (taken as a mixture of diasteromers): δ (major diastereomer): 7.37~6.68 (m, 10H), 5.99 (dt, J=16.8, 9.6 Hz, 1H), 4.99 (dd, J=10.0, 1.2 Hz, 1H), 4.89 (d, J=16.8 Hz, 1H), 3.50 (d, J=9.2 Hz, 1H), 3.31 (d, J=13.6 Hz, 1H), 2.59 (d, J=13.2 Hz, 1H), 1.32 (s, 3H); δ (minor diastereomer): 6.15 (dt, J=17.2, 10.0 Hz, 1H), 5.15~5.12 (m, 2H), 3.46 (d, J=10.0 Hz, 1H), 3.20 (d, J=13.6 Hz, 1H), 2.81 (d, J=13.2 Hz, 1H), 1.41 (s, 3H); 13C NMR (101 MHz, CDCl3) (taken as a mixture of diasteromers) δ:143.2, 143.1, 141.0 (2C), 138.1, 137.7, 129.7, 129.2, 128.0, 127.9 (2C), 127.7, 127.4, 126.4, 126.2, 126.1, 126.0, 117.0, 116.6, 60.3, 59.8, 51.4, 51.1, 46.7, 46.6, 19.8, 19.5; IR (Neat) v: 3084, 3059, 2923, 1599, 1494, 1447, 1029, 914, 777, 698 cm-1; MS (ESI) m/z: 252 [M+H]+; HRMS (ESI) calcd for C18H22N [M+H]+: 252.1747, found 252.1748.

    3.2.3   2-甲基-2, 3-二苯基-4-戊烯醛(7)的合成

    氩气保护下, 在25 mL Schlenk反应管中加入3a (30.0 mg, 0.12 mmol)和甲苯(1.0 mL), -30 ℃下加入DIBAL-H (0.24 mL, 1.0 mol•L-1 in hexane, 0.24 mmol), 加毕后于此温度下反应过夜.加入饱和酒石酸钾钠水溶液小心淬灭至无气泡产生, 乙酸乙酯萃取(10 mL×3), 无水硫酸钠干燥, 过滤, 减压除去溶剂, 粗产品硅胶快速柱层析纯化[V(石油醚):V(乙酸乙酯)=20:1]得到无色液体7 26.7 mg, 产率89%. 1H NMR (400 MHz, CDCl3) δ (taken as a mixture of diasteromers): δ (major diastereomer): 9.83 (s, 1H), 7.40~6.83 (m, 10H), 6.16 (dt, J=16.4, 9.6 Hz, 1H), 5.22 (d, J=10.8 Hz, 1H), 5.17 (d, J=16.4 Hz, 1H), 4.21 (d, J=8.8 Hz, 1H), 1.50 (s, 3H); δ(minor diastereomer): 9.74 (s, 1H), 5.95 (dt, J=16.8, 10.0 Hz, 1H), 5.05 (d, J=9.6 Hz, 1H), 5.03 (d, J=16.8 Hz, 1H), 4.16 (d, J=8.8 Hz, 1H), 1.39 (s, 3H); 13C NMR (101 MHz, CDCl3) (taken as a mixture of diasteromers) δ: 202.4 (2C), 139.6, 139.4, 138.6, 138.0, 137.0, 136.6, 129.8, 129.5, 128.7, 128.3, 128.2, 127.9 (2C), 127.7, 127.4, 127.2, 126.8, 126.5, 118.4, 117.7, 57.6, 57.4, 55.6, 55.4, 17.9, 16.9; IR (Neat) v: 3060, 3029, 2928, 2712, 1722, 1636, 1494, 1448, 1076, 920, 759, 699, 536 cm-1; MS (EI) m/z: 250 (M+, 0.5), 206 (5), 191 (29), 117 (100), 91 (14), 77 (7), 57 (6); HRMS (EI) calcd for C18H18O: 250.1358, found 250.1359.

    3.2.4   3, 4-二苯基戊烯(8)的合成

    氩气保护下, 在25 mL Schlenk反应管中加入3a (40.0 mg, 0.16 mmol)和四氢呋喃(0.5 mL), 0 ℃下加入MeLi (0.25 mL, 1.6 mol•L-1 in THF, 0.4 mmol), 加毕后恢复室温反应过夜.加入1.0 mL水淬灭, 乙酸乙酯萃取(10 mL×3), 无水硫酸钠干燥, 过滤, 减压除去溶剂, 粗产品硅胶快速柱层析纯化[V(石油醚):V(乙酸乙酯)=20:1]得到无色液体8 32.4 mg, 产率91%[10]. 1H NMR (400 MHz, CDCl3) δ(taken as a mixture of diasteromers): δ (major diastereomer): 7.33~6.97 (m, 10H), 5.83 (dt, J=16.8, 9.6 Hz, 1H), 4.82 (d, J=10.0 Hz, 1H), 4.73 (d, J=17.2 Hz, 1H), 3.42~3.36 (m, 1H), 3.10~3.01 (m, 1H), 1.08 (d, J=6.8 Hz, 3H); δ (minor diastereomer): 6.08 (dt, J=17.2, 9.6 Hz, 1H), 5.11~5.06 (m, 2H), 3.42~3.36 (m, 1H), 3.10~3.01 (m, 1H), 1.32 (d, J=7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) (taken as a mixture of diasteromers)δ: 145.5, 145.3, 143.4, 143.3, 140.6, 140.5, 128.4, 128.2, 128.1, 128.0, 127.9 (2C), 127.8, 127.7, 126.3, 126.1, 125.8, 125.7, 115.6, 115.3, 58.2, 57.4, 45.4, 45.0, 20.7, 20.2.

    辅助材料(Supporting Information)  化合物1, 2, 59的合成[6c, 6e, 11], 化合物310的核磁谱图和3d的单晶X衍射分析数据.这些材料可以免费从本刊网站(http://sioc-journal.cn/)上下载.


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  • 图式 1  钯催化烯丙基烷基化反应

    Scheme 1  Pd-catalyzed allylic alkylation

    图式 2  Pd/NHC催化腈的烯丙基烷基化反应的可能反应历程

    Scheme 2  Proposed reaction process of Pd/NHC catalyzed allylic alkylation of nitriles

    图式 3  产物的衍生化

    Scheme 3  Synthetic transformation of the products

    图式 4  环状烯丙基试剂9的烯丙基烷基化反应

    Scheme 4  Allylic alkylation reaction of allyl reagent 9

    表 1  配体、钯源、温度和溶剂对反应的影响a

    Table 1.  Influence of ligand, Pd source, temperature and solvent on the reaction

    Entry Ligand [Pd] T/℃ Solvent Yieldb/% of 3a n(B)/n(L)b drb of 3a
    1 L1 [Pd(η3-C3H5)Cl]2 25 THF 14 18/82 1.5:1
    2 L2 [Pd(η3-C3H5)Cl]2 25 THF 9 11/89 1:1
    3 L3 [Pd(η3-C3H5)Cl]2 25 THF 0 0/100
    4 L4 [Pd(η3-C3H5)Cl]2 25 THF 62 69/31 1.1:1
    5 L5 [Pd(η3-C3H5)Cl]2 25 THF 41 41/59 1:1
    6 (R)-Binap [Pd(η3-C3H5)Cl]2 25 THF 31 31/69 1.1:1
    7 (S)-iPr-Phox [Pd(η3-C3H5)Cl]2 25 THF 33 35/65 1.2:1
    8 L4 Pd(PPh3)4 25 THF 18 22/78 1:1
    9 L4 Pd(PPh3)2Cl2 25 THF 20 23/77 1:1
    10 L4 [Pd(π-cinnamyl)Cl]2 25 THF 57 59/41 1.1:1
    11 L4 [Pd(η3-C3H5)Cl]2 0 THF 59 59/41 1:1
    12 L4 [Pd(η3-C3H5)Cl]2 60 THF 45 55/45 1.1:1
    13 L4 [Pd(η3-C3H5)Cl]2 25 DME 62 70/30 1.2:1
    14 L4 [Pd(η3-C3H5)Cl]2 25 Dioxane 50 54/46 1:1
    15 L4 [Pd(η3-C3H5)Cl]2 25 Et2O 38 45/55 1:1
    16 L4 [Pd(η3-C3H5)Cl]2 25 Toluene 45 54/46 1.1:1
    17 L4 [Pd(η3-C3H5)Cl]2 25 DMSO 49 78/22 1.8:1
    a Reaction conditions: [Pd(η3-C3H5)Cl]2/L/1a/2a/LiHMDS=2.5/5/200/100/200;b Determined by 1H NMR.
    下载: 导出CSV

    表 2  使用支链烯丙基试剂条件下溶剂和温度对反应的影响a

    Table 2.  Influence of solvent and temperature on the reaction using branched allyl reagent

    Entry Solvent T/℃ 3ab/% n(B)/n(L)b drb of 3a
    1 THF 25 87 89/11 1:1
    2 Dioxane 25 88 95/5 1.1:1
    3 DME 25 83 83/17 1:1
    4 Toluene 25 89 89/11 1.1:1
    5 Hexane 25 91 96/4 1.2:1
    6 Hexane 0 85 93/7 1.3:1
    7 Hexane 60 88 95/5 1.2:1
    a Reaction conditions: [Pd(η3-C3H5)Cl]2/L4/1a/5a/LiHMDS=2.5/5/200/100/ 200; b Determined by 1H NMR.
    下载: 导出CSV

    表 3  反应的底物拓展a

    Table 3.  Substrate scope of the reaction

    a Reaction conditions: [Pd(η3-C3H5)Cl]2/L4/1a/5a/LiHMDS=2.5/5/200/100/200; regio- and diastereo-selectivities were determined by 1H NMR; isolated yield; b relative configuration of 3d; c nd=not detected; d reaction temperature: 60 ℃; e [Pd(η3-C3H5)Cl]2: 5.0 mol%, L4: 10 mol%.
    下载: 导出CSV
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  • 发布日期:  2020-10-25
  • 收稿日期:  2020-06-05
  • 修回日期:  2020-06-23
  • 网络出版日期:  2020-06-30
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