CN105801382A - 一种芳基烯烃类化合物的合成方法 - Google Patents
一种芳基烯烃类化合物的合成方法 Download PDFInfo
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- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 13
- 239000003960 organic solvent Substances 0.000 claims abstract description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 7
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- 238000004519 manufacturing process Methods 0.000 abstract 1
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/001—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by modification in a side chain
- C07C37/003—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by modification in a side chain by hydrogenation of an unsaturated part
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B35/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving a change in the type of bonding between two carbon atoms already directly linked
- C07B35/02—Reduction
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- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/68—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
- C07C209/70—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton by reduction of unsaturated amines
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- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/20—Preparation of ethers by reactions not forming ether-oxygen bonds by hydrogenation of carbon-to-carbon double or triple bonds
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- C07F7/02—Silicon compounds
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- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
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Abstract
本发明公开了一种芳基烯烃类化合物的合成方法，属于有机化学合成领域。具体地说，在氮气氛围下，将邻羟基（氨基）芳基炔烃类化合物、双联频哪醇硼酸酯化合物、过渡金属（铑或铱或钯或铂）化合物、碱以及氢源溶解在有机溶剂中，加热搅拌反应，反应结束后，减压除去有机溶剂，进行柱色谱分离，制得各种邻羟基（氨基）芳基烯烃类化合物。本发明合成步骤简单、反应条件温和、操作简便易行、产物收率高，达80%以上，能够有效地抑制环合产物苯并呋喃或吲哚衍生物的生成，为邻羟基（氨基）芳基烯烃类化合物的合成提供了一种新途径。与现有方法比，原料廉价易得，且不需要无水条件下反应，简化了反应步骤，提高了反应的效率和反应的原子经济性。
Description
技术领域
本发明属于芳基烯烃类化合物合成技术领域，具体涉及一种邻羟基二苯乙烯或邻氨基二苯乙烯类化合物的合成方法。
背景技术
芳基烯烃类化合物因其广泛的生物活性而成为医药化学中比较珍贵的物质[Sviripa,V.M.；Zhang,W.；Balia,A.G.；etal.J.Med.Chem.2014,57,6083.]，尤其是羟基化的二苯乙烯类，它们广泛地存在于自然界中[(a)Riviere,C.；Pawlus,A.D.；Merillon,J.M.Nat.Prod.Rep.2012,29,1317.(b)Shen,T.；Wang,X.N.；Lou,H.X.Nat.Prod.Rep.2009,26,916.]，因为其普遍具有抗氧化性、抗癌抗菌性等而扮演着愈来愈重要的角色，它们可用于心血管病[Bradamante,S.；Barenghi,L.；Villa,A.DrugRev.2004,22,169.]和一些癌症的治疗药物中[Aggerwal,B.B.；Bhardwaj,A.；Aggarwal,R.S.；etal.AnticancerRes.2004,24,2783.]。因此，合成这类物质以及对类似物质的生物活性评价便受到医药化学界的热切关注[(a)Csuk,R.；Albert,S.；Siewert,B.；etal.J.Med.Chem.2012,54,669.(b)Shard,A.；Sharma,N.；Bharti,R.；etal.Angew.Chem.Int.Ed.2012,51,12250.]。常用的合成这类烯烃的反应则是Wittig反应[(a)Wittig,G.；Schollkopf,U.Chem.Ber.1954,97,1318.(b)Kikumoto,R.；Hara,H.；Tamao,Y.；etal.J.Med.Chem.1990,33,1818.(c)Ali,M.A.；Kondo,K.；Tsuda,Y.Chem.Pharm.Bull.1992,40,1130.]以及Heck反应[(a)Heck,R.F.Org.React.1982,27,345.(b)Huang,S.H.；Chen,J.R.；Tsai,F.Y.Molecules2010,15,315.(c)Martí-Centelles,R.；Falomir,E.；Carda,M.；etal.Bioorg.Med.Chem.2013,21,3010.(d)Schmidt,B.；Berger,R.；F.Org.Biomol.Chem.2013,11,3674.]，另外文献报道的也有使用氧化偶联的方法来制备芳基烯烃类化合物[(a)Shen,Y.；Liu,G.；Lu,X.；etal.Org.Lett.2013,15,3366.(b)Fukutani,T.；Hirano,K.；Satoh,T.；etal.Org.Lett.2009,11,5198.]。尽管这些合成方法路线成熟，但是反应条件苛刻，所使用的原料也大多以端基烯为主，少有以炔烃为原料直接还原的方法报道，因此，寻找高效快捷的合成芳基烯烃类化合物的新方法亟待发展。
众所周知，以邻羟基(氨基)芳基炔烃类化合物一般能够发生的是环化反应，未见有报道提出其发生反应后主产物为邻羟基(氨基)芳基烯烃类化合物。最近，Ong研究组报道了IPrG-CuCl催化的双联频哪醇硼酸酯试剂与芳基炔烃的硼氢化还原反应，但是在加入叔丁醇锂后却意外地得到了顺式的氢化产物烯烃[Ong,T.；Tai,C.Chem.Commun.2014,50,4344.]；Yun课题组报道了铜催化双取代的炔烃的硼化加成来合成具有高度区域选择性和立体选择性的烯基硼酸酯类化合物，研究中意外发现对2-吡啶叔丁基乙炔的反应却生成了反式烯烃氢化产物[Yun,J.；Kim,H.Chem.Commun.2011,47,2943.]。这两个关于芳基炔烃的硼化/去硼化/质子化还原反应均是以一种特殊的例子加以报道，而非是对炔烃的氢化还原做专门的研究。而通过过渡金属催化邻羟基(氨基)芳基炔烃类化合物的硼化/质子化串联反应来找到一种条件温和、环境友好且能高效快捷合成邻羟基(氨基)芳基烯烃类化合物的新方法还未见文献报道。
发明内容
本发明的目的是提供一种条件温和、环境友好且能直接利用邻羟基(氨基)芳基炔烃类化合物的硼化/质子化串联反应来合成邻羟基(氨基)芳基烯烃类化合物的新方法，通过该反应方法能够有效地抑制环合产物苯并呋喃或吲哚衍生物的生成，在有机合成方法学上具有一定的创新性和其独特的研究意义。
为实现上述目的，本发明采用以下技术方案：
一种芳基烯烃类化合物的合成方法，步骤如下：在氮气氛围下，将芳基炔烃类化合物、双联频哪醇硼酸酯化合物、过渡金属化合物、碱以及氢源溶解在有机溶剂中，在25-120℃的条件下搅拌反应1-4h，反应结束后，减压除去有机溶剂，进行柱色谱分离，制得芳基烯烃类化合物，所述芳基烯烃类化合物具有如下通式：
通式中R1为羟基、氨基或取代氨基；R2为不同取代的芳基或TMS。芳基炔烃类化合物、双联频哪醇硼酸酯化合物、过渡金属化合物、碱的摩尔比为1：1.2：0.0125-0.05:3。
所述的氢源与芳基炔烃类化合物的摩尔比为3-30:1。
所述的芳基炔烃类化合物，具有以下通式：
通式中R1为羟基、氨基或取代氨基；R2为不同取代的芳基或TMS。所述的双联频哪醇硼酸酯化合物的结构式为：
所述的过渡金属化合物为[Rh(cod)Cl]2、Rh(PPh3)3Cl、[Ir(cod)Cl]2、PdCl2、Pd2(dba)3、PdCl2(dppf)、PdCl2(PPh3)2、Pd(OAc)2或PtCl2。
所述的碱为碳酸钾、碳酸钠、甲酸钠、氢氧化铯、叔丁醇钠、碳酸铯、三乙胺或乙酸钾。
所述的氢源为水、苯酚或异丙醇。
所述的有机溶剂为1,4-二氧六环、甲苯、氯仿、四氢呋喃、N,N-二甲基甲酰胺、二甲亚砜或乙腈。
本发明的有益效果：本发明提供了一种通过过渡金属铑催化邻羟基(氨基)芳基炔烃类化合物的硼化/质子化串联反应来制备邻羟基(氨基)芳基烯烃类化合物的新方法。合成步骤简单、反应条件温和、操作简便易行、产物收率高，达80％以上，为邻羟基(氨基)芳基烯烃类化合物的合成提供了一种新途径。与现有方法比，原料廉价易得，且不需要无水条件下反应，简化了反应步骤，提高了反应的效率和反应的原子经济性。更值得一提的是，该反应能够有效地抑制环合产物苯并呋喃或吲哚衍生物的生成，在有机合成方法学上具有一定的创新性和其独特的研究意义。
附图说明
图1为本发明邻羟基(氨基)芳基烯烃类化合物C的X-射线单晶衍射图。
具体实施方式
下面结合具体实施例，对本发明做进一步说明。应理解，以下实施例仅用于说明本发明而非用于限制本发明的范围，该领域的技术熟练人员可以根据上述发明的内容作出一些非本质的改进和调整。
实施例1
化合物A的制备方法：
向干燥的25mLSchlenk反应管中加入邻羟基二苯乙炔化合物(38.8mg,0.2mmol)，然后依次加入双联频哪醇硼酸酯(60.9mg,0.24mmol)、[Rh(cod)Cl]2(2.5mg,0.005mmol)、乙酸钾(58.9mg,0.6mmol)，在氮气保护下，加入1,4-二氧六环(0.8mL)、水(0.2mL)，25℃反应4h。反应结束后，减压除去溶剂，柱色谱分离(石油醚/乙酸乙酯＝20/1，体积比)得到目标产物A。该化合物的实验数据：Whitesolid,isolatedyield82％,mp:147℃；1HNMR(600MHz,CDCl3,SiMe4):δ7.52(d,J＝7.8Hz,3H,CH),7.34-7.38(m,3H,CH),7.24-7.26(m,1H,CH),7.10-7.15(m,2H,CH),6.95(d,J＝7.8Hz,1H,CH),6.79(dd,J＝0.6,7.8Hz,1H,CH),5.02(s,1H,OH)；13CNMR(600MHz,CDCl3,SiMe4):δ155.5,138.2,129.2,129.1,128.2,127.7,127.0,126.7,124.2,124.1,119.8,116.3；HRMScalcd.forC14H12O[M+H]+:197.0966,found197.0959.
实施例2
邻羟基芳基烯烃化合物B的制备：
向干燥的25mLSchlenk反应管中加入邻羟基二苯乙炔化合物(45.6mg,0.2mmol)，然后依次加入双联频哪醇硼酸酯(60.9mg,0.24mmol)、[Rh(cod)Cl]2(2.5mg,0.005mmol)、碳酸钾(82.8mg,0.6mmol)，在氮气保护下，加入甲苯(0.8mL)、异丙醇(444mg,6mmol)，120℃反应1h。反应结束后，减压除去溶剂，柱色谱分离(石油醚/甲苯＝10/1，体积比)得到目标产物B。该化合物的实验数据：Whitesolid,isolatedyield78％,mp:109-111℃；1HNMR(600MHz,CDCl3,SiMe4):δ7.50(dd,J＝1.2,7.8Hz,1H,CH),7.41-7.43(m,2H,CH),7.28-7.35(m,3H,CH),7.12-7.15(m,1H,CH),7.04-7.07(m,1H,CH),6.94(t,J＝7.2Hz,1H,CH),6.78(d,J＝7.8Hz,1H,CH),5.24(s,1H,OH)；13CNMR(600MHz,CDCl3,SiMe4):δ153.1,136.2,133.1,128.9,128.8,128.6,127.7,127.2,124.4,123.7,121.2,116.0；HRMScalcd.forC14H11ClO[M+H]+:231.0577,found231.0568.
实施例3
邻羟基芳基烯烃C的制备：
向干燥的25mLSchlenk反应管中加入邻羟基二苯乙炔化合物(44.8mg,0.2mmol)，然后依次加入双联频哪醇硼酸酯(60.9mg,0.24mmol)、[Rh(cod)Cl]2(5.00mg,0.01mmol)、碳酸钠(63.6mg,0.6mmol)，在氮气保护下，加入氯仿(0.8mL)、苯酚(564mg,6mmol)，100℃反应1.5h。反应结束后，减压除去溶剂，柱色谱分离(石油醚/氯仿＝20/1，体积比)得到目标产物C。该化合物的实验数据：Whitesolid,isolatedyield66％,mp:142-143℃；1HNMR(600MHz,CDCl3,SiMe4):δ7.49(d,J＝7.2Hz,1H,CH),7.46(d,J＝8.4Hz,2H,CH),7.21-7.23(m,1H,CH),7.04-7.12(m,2H,CH),6.93(t,J＝6.0Hz,1H,CH),6.89(d,J＝8.4Hz,2H,CH),6.78(d,J＝7.8Hz,1H,CH),5.13(s,1H,OH),3.82(s,3H,CH3)；13CNMR(600MHz,CDCl3,SiMe4):δ159.3,152.8,130.5,129.8,128.3,127.8,127.1,125.0,121.1,120.9,115.9,114.2,55.4；HRMScalcd.forC15H14O2[M+H]+:227.1072,found227.1065.
实施例4
邻羟基芳基烯烃D的制备：
向干燥的25mLSchlenk反应管中加入邻羟基二苯乙炔化合物(50.0mg,0.2mmol)，然后依次加入双联频哪醇硼酸酯(60.9mg,0.24mmol)、[Rh(cod)Cl]2(1.25mg,0.0025mmol)、甲酸钠(40.8mg,0.6mmol)，在氮气保护下，加入四氢呋喃(0.8mL)、水(0.2mL)，80℃反应2h。反应结束后，减压除去溶剂，柱色谱分离(石油醚/四氢呋喃＝15/1，体积比)得到目标产物D。该化合物的实验数据：Whitesolid,isolatedyield34％,mp:73-75℃；1HNMR(600MHz,CDCl3,SiMe4):δ7.51(d,J＝7.8Hz,1H,CH),7.47(d,J＝7.8Hz,2H,CH),7.31-7.39(m,3H,CH),7.08-7.14(m,2H,CH),6.94(t,J＝7.8Hz,1H,CH),6.80(d,J＝7.8Hz,1H,CH),5.08(s,1H,OH),1.33(s,9H,CH3)；13CNMR(600MHz,CDCl3,SiMe4):δ153.0,150.8,134.8,130.1,128.5,127.2,126.3,125.6,124.9,122.2,121.1,115.9,34.6,31.3；HRMScalcd.forC18H20O[M+H]+:253.1592,found253.1584.
实施例5
邻羟基芳基烯烃E的制备：
向干燥的25mLSchlenk反应管中加入邻羟基二苯乙炔化合物(42.4mg,0.2mmol)，然后依次加入双联频哪醇硼酸酯(60.9mg,0.24mmol)、[Rh(cod)Cl]2(2.00mg,0.004mmol)、氢氧化铯(90.0mg,0.6mmol)，在氮气保护下，加入乙腈(0.8mL)、异丙醇(444mg,6mmol)，70℃反应2.5h。反应结束后，减压除去溶剂，柱色谱分离(石油醚/乙腈＝30/1，体积比)得到目标产物E。该化合物的实验数据：Whitesolid,isolatedyield55％,mp:130-132℃；1HNMR(600MHz,CDCl3,SiMe4):δ7.47-7.51(m,3H,CH),7.25-7.29(m,1H,CH),7.13-7.16(m,1H,CH),7.02-7.09(m,3H,CH),6.95(t,J＝7.2Hz,1H,CH),6.80(d,J＝7.8Hz,1H,CH),4.98(s,1H,OH)；13CNMR(600MHz,CDCl3,SiMe4):δ163.2,161.5,153.0,133.9,128.9,128.7,128.1,128.0,127.2,124.6,122.9,116.0,115.9,115.7,115.5；HRMScalcd.forC14H11FO[M+H]+:215.0872,found215.0867.
实施例6
邻羟基芳基烯烃F的制备：
向干燥的25mLSchlenk反应管中加入邻羟基二苯乙炔化合物(54.4mg,0.2mmol)，然后依次加入双联频哪醇硼酸酯(60.9mg,0.24mmol)、[Rh(cod)Cl]2(5.00mg,0.01mmol)、叔丁醇钠(57.6mg,0.6mmol)，在氮气保护下，加入N,N-二甲基甲酰胺(0.8mL)、苯酚(564mg,6mmol)，60℃反应2.5h。反应结束后，减压除去溶剂，柱色谱分离(石油醚/N,N-二甲基甲酰胺＝40/1，体积比)得到目标产物F。该化合物的实验数据：Whitesolid,isolatedyield51％,mp:101-102℃；1HNMR(600MHz,CDCl3,SiMe4):δ7.71(dd,J＝1.2,7.8Hz,1H,CH),7.57-7.59(m,2H,CH),7.30-7.49(m,3H,CH),7.16-7.19(m,1H,CH),7.10-7.13(m,1H,CH),6.97(t,J＝7.2Hz,1H,CH),6.80(dd,J＝0.6,7.8Hz,1H,CH),5.06(s,1H,OH)；13CNMR(600MHz,CDCl3,SiMe4):δ153.2,137.5,133.0,129.1,128.8,128.7,127.6,127.5,126.9,125.9,124.4,124.1,121.2,116.0；HRMScalcd.forC14H11BrO[M+H]+:275.0072,found275.0065.
实施例7
邻羟基芳基烯烃G的制备：
向干燥的25mLSchlenk反应管中加入邻羟基二苯乙炔化合物(45.2mg,0.2mmol)，然后依次加入双联频哪醇硼酸酯(60.9mg,0.24mmol)、[Rh(cod)Cl]2(3.00mg,0.006mmol)、碳酸铯(195.5mg,0.6mmol)，在氮气保护下，加入二甲亚砜(0.8mL)、水(0.2mL)，50℃反应3h。反应结束后，减压除去溶剂，柱色谱分离(石油醚/二甲亚砜＝50/1，体积比)得到目标产物G。该化合物的实验数据：Whitesolid,isolatedyield73％,mp:130-131℃；1HNMR(600MHz,CDCl3,SiMe4):δ7.71(dd,J＝1.2,7.8Hz,1H,CH),7.58(dd,J＝0.6,7.8Hz,1H,CH),7.51-7.53(m,1H,CH),7.34-7.39(m,2H,CH),7.24-7.27(m,1H,CH),7.13-7.20(m,2H,CH),6.97(t,J＝7.8Hz,1H,CH),6.80(dd,J＝0.6,7.8Hz,1H,CH),5.07(s,1H,OH)；13CNMR(600MHz,CDCl3,SiMe4):δ153.1,135.8,133.4,129.8,129.1,128.7,128.5,127.5,126.9,126.6,126.0,125.6,124.5,121.3,116.0；HRMScalcd.forC14H11ClO[M+H]+:231.0577,found231.0571.
实施例8
邻羟基芳基烯烃H的制备：
向干燥的25mLSchlenk反应管中加入邻羟基二苯乙炔化合物(41.6mg,0.2mmol)，然后依次加入双联频哪醇硼酸酯(60.9mg,0.24mmol)、[Rh(cod)Cl]2(2.00mg,0.004mmol)、三乙胺(60.6mg,0.6mmol)，在氮气保护下，加入甲苯(0.8mL)、异丙醇(444mg,6mmol)，50℃反应3h。反应结束后，减压除去溶剂，柱色谱分离(石油醚/甲苯＝10/1，体积比)得到目标产物H。该化合物的实验数据：Whitesolid,isolatedyield76％,mp:113-115℃；1HNMR(600MHz,CDCl3,SiMe4):δ7.62(d,J＝7.8Hz,1H,CH),7.52(d,J＝7.8Hz,1H,CH),7.14-7.35(m,6H,CH),6.96(t,J＝7.8Hz,1H,CH),6.81(d,J＝8.4Hz,1H,CH),5.07(s,1H,OH),2.42(s,3H,CH3)；13CNMR(600MHz,CDCl3,SiMe4):δ153.0,136.7,135.8,130.4,128.7,128.3,127.6,127.5,126.2,125.5,125.1,124.3,121.1,116.0,19.9；HRMScalcd.forC15H14O[M+H]+:211.1123,found211.1116.
实施例9
邻羟基芳基烯烃I的制备：
向干燥的25mLSchlenk反应管中加入邻羟基二苯乙炔化合物(52.4mg,0.2mmol)，然后依次加入双联频哪醇硼酸酯(60.9mg,0.24mmol)、[Rh(cod)Cl]2(5.00mg,0.01mmol)、叔丁醇钠(57.6mg,0.6mmol)，在氮气保护下，加入氯仿(0.8mL)、苯酚(564mg,6mmol)，40℃反应3.5h。反应结束后，减压除去溶剂，柱色谱分离(石油醚/氯仿＝20/1，体积比)得到目标产物I。该化合物的实验数据：Whitesolid,isolatedyield59％,mp:123-125℃；1HNMR(600MHz,CDCl3,SiMe4):δ7.50(d,J＝7.8Hz,1H,CH),7.38-7.41(m,3H,CH),7.23(s,1H,CH),7.17(t,J＝7.8Hz,1H,CH),6.95-7.02(m,2H,CH),6.80(d,J＝7.8Hz,1H,CH),5.12(s,1H,OH)；13CNMR(600MHz,CDCl3,SiMe4):δ153.3,140.9,135.2,129.4,127.4,127.1,127.0,126.1,124.8,123.8,121.3,116.0；HRMScalcd.forC14H10Cl2O[M+H]+:265.0187,found265.0183.
实施例10
邻氨基芳基烯烃J的制备：
向干燥的25mLSchlenk反应管中加入邻羟基二苯乙炔化合物(38.6mg,0.2mmol)，然后依次加入双联频哪醇硼酸酯(60.9mg,0.24mmol)、[Rh(cod)Cl]2(4.0mg,0.008mmol)、碳酸钾(82.8mg,0.6mmol)，在氮气保护下，加入乙腈(0.8mL)、异丙醇(444mg,6mmol)，70℃反应3h。反应结束后，减压除去溶剂，柱色谱分离(石油醚/乙腈＝30/1，体积比)得到目标产物J。该化合物的实验数据：Whitesolid,isolatedyield85％,mp:100-101℃；1HNMR(600MHz,CDCl3,SiMe4):δ7.47(d,J＝7.8Hz,2H,CH),7.38(d,J＝7.8Hz,1H,CH),7.33(t,J＝7.2Hz,2H,CH),7.23(t,J＝7.2Hz,1H,CH),7.06-7.1(m,2H,CH),6.96(d,J＝16.2Hz,1H,CH),6.78(t,J＝7.2Hz,1H,CH),6.67(d,J＝7.8Hz,1H,CH),3.67(s,2H,NH2)；13CNMR(600MHz,CDCl3,SiMe4):δ144.1,137.7,130.4,128.8,128.7,127.7,127.3,126.5,124.4,124.0,119.2,116.4；HRMScalcd.forC14H13N[M+H]+:196.1126,found196.1122.
实施例11
邻氨基芳基烯烃K的制备：
向干燥的25mLSchlenk反应管中加入邻羟基二苯乙炔化合物(58.6mg,0.2mmol)，然后依次加入双联频哪醇硼酸酯(60.9mg,0.24mmol)、[Rh(cod)Cl]2(5.0mg,0.01mmol)、乙酸钾(58.9mg,0.6mmol)，在氮气保护下，加入1,4-二氧六环(0.8mL)、水(0.2mL)，25℃反应4h。反应结束后，减压除去溶剂，柱色谱分离(石油醚/乙酸乙酯＝20/1，体积比)得到目标产物K。该化合物的实验数据：Whitesolid,isolatedyield50％,mp:79-82℃；1HNMR(600MHz,CDCl3,SiMe4):δ7.93(d,J＝6.0Hz,1H,NH),7.14-7.18(m,1H,CH),7.04-7.09(m,6H,CH),6.87(t,J＝7.2Hz,1H,CH),6.65(d,J＝12.6Hz,1H,CH),6.41-6.45(m,2H,CH),1.33(s,9H,CH3)；13CNMR(600MHz,CDCl3,SiMe4):δ151.6,135.0,134.5,132.3,128.1,127.7,127.3,127.2,126.8,125.7,125.6,124.3,121.9,79.2,27.2；HRMScalcd.forC19H21NO2[M-boc+2H]+:196.1126,found196.1123.
实施例12
邻羟基芳基烯烃L的制备：
向干燥的25mLSchlenk反应管中加入邻羟基二苯乙炔化合物(38.0mg,0.2mmol)，然后依次加入双联频哪醇硼酸酯(60.9mg,0.24mmol)、[Rh(cod)Cl]2(5.00mg,0.01mmol)、叔丁醇钠(57.6mg,0.6mmol)，在氮气保护下，加入N,N-二甲基甲酰胺(0.8mL)、苯酚(564mg,6mmol)，30℃反应4h。反应结束后，减压除去溶剂，柱色谱分离(石油醚/N,N-二甲基甲酰胺＝60/1，体积比)得到目标产物L。该化合物的实验数据：Colourlessoil,isolatedyield39％；1HNMR(600MHz,CDCl3,SiMe4):δ7.43(dd,J＝1.2,7.8Hz,1H,CH),7.11-7.16(m,2H,CH),6.91(t,J＝7.8Hz,1H,CH),6.79(d,J＝7.8Hz,1H,CH),6.45(d,J＝19.2Hz,1H,CH),5.14(s,1H,OH),0.17(s,9H,CH3)；13CNMR(600MHz,CDCl3,SiMe4):δ154.0,139.0,132.9,130.2,128.3,127.0,122.1,117.2；HRMScalcd.forC11H16OSi[M+H]+:193.1049,found193.1042.
1、反应条件优化实验：不同的催化剂、溶剂、碱、温度、催化剂的量和氢源催化邻羟基(氨基)芳基炔烃类化合物的硼化/质子化串联反应，得到不同收率的邻羟基(氨基)芳基烯烃类化合物。
2、催化剂的优化实验：向干燥的25mLSchlenk反应管中加入邻羟基二苯乙炔化合物(38.8mg,0.2mmol)，然后依次加入双联频哪醇硼酸酯(60.9mg,0.24mmol)、不同的催化剂(0.005mmol)、乙酸钾(58.9mg,0.6mmol)，在氮气保护下，加入1,4-二氧六环(0.8mL)、水(0.2mL)，室温(25℃)反应4h。反应结束后，减压除去溶剂，柱色谱分离(石油醚/乙酸乙酯＝20/1，体积比)得到目标产物A。
不同的催化剂催化邻羟基二苯乙炔的硼化/质子化串联反应，获得不同的催化结果(表1)。
表1不同的催化剂催化邻羟基二苯乙炔的硼化/质子化串联反应的实验结果
a不反应；b主产物为2-苯基苯并呋喃。
3、溶剂的优化实验：向干燥的25mLSchlenk反应管中加入邻羟基二苯乙炔化合物(38.8mg,0.2mmol)，然后依次加入双联频哪醇硼酸酯(60.9mg,0.24mmol)、[Rh(cod)Cl]2(2.5mg,0.005mmol)、乙酸钾(58.9mg,0.6mmol)，在氮气保护下，加入不同的溶剂(0.8mL)、水(0.2mL)，室温(25℃)反应4h。反应结束后，减压除去溶剂，柱色谱分离(石油醚/乙酸乙酯＝20/1，体积比)得到目标产物A。
不同的溶剂下催化邻羟基二苯乙炔的硼化/质子化串联反应，获得不同的催化结果(表2)。
表2不同的溶剂下催化邻羟基二苯乙炔的硼化/质子化串联反应的实验结果
4、碱的优化实验：向干燥的25mLSchlenk反应管中加入邻羟基二苯乙炔化合物(38.8mg,0.2mmol)，然后依次加入双联频哪醇硼酸酯(60.9mg,0.24mmol)、[Rh(cod)Cl]2(2.5mg,0.005mmol)、不同的碱(0.6mmol)，在氮气保护下，加入1,4-二氧六环(0.8mL)、水(0.2mL)，室温(25℃)反应4h。反应结束后，减压除去溶剂，柱色谱分离(石油醚/乙酸乙酯＝20/1，体积比)得到目标产物A。
不同的碱中发生邻羟基二苯乙炔的硼化/质子化串联反应，获得不同的催化结果(表3)。
表3不同的碱中催化邻羟基二苯乙炔的硼化/质子化串联反应的实验结果
a10％转化率；b主产物为2-苯基苯并呋喃。
5、温度和催化剂的量的优化实验：向干燥的25mLSchlenk反应管中加入邻羟基二苯乙炔化合物(38.8mg,0.2mmol)，然后依次加入双联频哪醇硼酸酯(60.9mg,0.24mmol)、不同量的[Rh(cod)Cl]2、乙酸钾(58.9mg,0.6mmol)，在氮气保护下，加入1,4-二氧六环(0.8mL)、水(0.2mL)，25～120℃下反应4h。反应结束后，减压除去溶剂，柱色谱分离(石油醚/乙酸乙酯＝20/1，体积比)得到目标产物A。
不同的碱中发生邻羟基二苯乙炔的硼化/质子化串联反应，获得不同的催化结果(表4)。
表4不同的温度和不同催化剂的量对邻羟基二苯乙炔的硼化/质子化串联反应的实验影响结果
6、氢源的优化实验：向干燥的25mLSchlenk反应管中加入邻羟基二苯乙炔化合物(38.8mg,0.2mmol)，然后依次加入双联频哪醇硼酸酯(60.9mg,0.24mmol)、[Rh(cod)Cl]2(2.5mg,0.005mmol)、乙酸钾(58.9mg,0.6mmol)，在氮气保护下，加入1,4-二氧六环(0.8mL)、不同氢源，室温(25℃)反应4h。反应结束后，减压除去溶剂，柱色谱分离(石油醚/乙酸乙酯＝20/1，体积比)得到目标产物A。
不同的氢源下发生邻羟基二苯乙炔的硼化/质子化串联反应，获得不同的催化结果(表5)。
表5不同的氢源对邻羟基二苯乙炔的硼化/质子化串联反应的实验影响结果
a不加氢源，所使用的碱和溶剂均经过干燥处理，无水反应；
b加入2当量水；c0.2mL1,4-二氧六环，0.8mL水。
以上显示和描述了本发明的基本原理和主要特征以及本发明的优点。本行业的技术人员应该了解，本发明不受上述实施例的限制，上述实施例和说明书中描述的只是说明本发明的原理，在不脱离本发明精神和范围的前提下，本发明还会有各种变化和改进，这些变化和改进都落入要求保护的本发明范围内。本发明要求保护范围由所附的权利要求书及其等效物界定。
Claims (9)
1.一种芳基烯烃类化合物的合成方法，其特征在于步骤如下：在氮气氛围下，将芳基炔烃类化合物、双联频哪醇硼酸酯化合物、过渡金属化合物、碱以及氢源溶解在有机溶剂中，在25-120℃的条件下搅拌反应1-4h，反应结束后，减压除去有机溶剂，进行柱色谱分离，制得芳基烯烃类化合物，所述芳基烯烃类化合物具有如下通式：
通式中R1为羟基、氨基或取代氨基；R2为不同取代的芳基或TMS。
2.根据权利要求1所述的芳基烯烃类化合物的合成方法，其特征在于：芳基炔烃类化合物、双联频哪醇硼酸酯化合物、过渡金属化合物、碱的摩尔比为1：1.2：0.0125-0.05:3。
3.根据权利要求1所述的芳基烯烃类化合物的合成方法，其特征在于：所述的氢源与芳基炔烃类化合物的摩尔比为3-30:1。
4.根据权利要求1所述的芳基烯烃类化合物的合成方法，其特征在于：所述的芳基炔烃类化合物，具有以下通式：
通式中R1为羟基、氨基或取代氨基；R2为不同取代的芳基或TMS。
5.根据权利要求1所述的芳基烯烃类化合物的合成方法，其特征在于：所述的双联频哪醇硼酸酯化合物的结构式为：
6.根据权利要求1所述的芳基烯烃类化合物的合成方法，其特征在于：所述的过渡金属化合物为[Rh(cod)Cl]2、Rh(PPh3)3Cl、[Ir(cod)Cl]2、PdCl2、Pd2(dba)3、PdCl2(dppf)、PdCl2(PPh3)2、Pd(OAc)2或PtCl2。
7.根据权利要求1所述的芳基烯烃类化合物的合成方法，其特征在于：所述的碱为碳酸钾、碳酸钠、甲酸钠、氢氧化铯、叔丁醇钠、碳酸铯、三乙胺或乙酸钾。
8.根据权利要求1所述的芳基烯烃类化合物的合成方法，其特征在于：所述的氢源为水、苯酚或异丙醇。
9.根据权利要求1所述的芳基烯烃类化合物的合成方法，其特征在于：所述的有机溶剂为1,4-二氧六环、甲苯、氯仿、四氢呋喃、N,N-二甲基甲酰胺、二甲亚砜或乙腈。
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110803973A (zh) * | 2019-11-14 | 2020-02-18 | 郑州大学 | 一种羧酸还原成醛类化合物的方法 |
| CN114539305A (zh) * | 2022-02-24 | 2022-05-27 | 川北医学院 | 一种通过对苯并呋喃去芳构化制备双键有机化合物的方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103435448A (zh) * | 2013-09-05 | 2013-12-11 | 南京工业大学 | 一种高立体选择性还原炔胺类化合物的方法 |
| CN104603142A (zh) * | 2012-04-06 | 2015-05-06 | 力奇制药公司 | 烯烃和炔烃中间体的β-硼化 |
-
2016
- 2016-05-30 CN CN201610371391.7A patent/CN105801382B/zh active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104603142A (zh) * | 2012-04-06 | 2015-05-06 | 力奇制药公司 | 烯烃和炔烃中间体的β-硼化 |
| CN103435448A (zh) * | 2013-09-05 | 2013-12-11 | 南京工业大学 | 一种高立体选择性还原炔胺类化合物的方法 |
Non-Patent Citations (2)
| Title |
|---|
| DIPANKAR SRIMANI, ET AL.,: "Iron Pincer Complex Catalyzed, Environmentally Benign, E-Selective Semi-Hydrogenation of Alkynes", 《ANGEW. CHEM. INT. ED.》 * |
| HYE RYUNG KIM ET AL.,: "Highly region- and stereoselective synthesis of alkenylboronic esters by copper-catalyzed boron additions to disubstituted alkynes", 《CHEM. COMMUN.》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110803973A (zh) * | 2019-11-14 | 2020-02-18 | 郑州大学 | 一种羧酸还原成醛类化合物的方法 |
| CN110803973B (zh) * | 2019-11-14 | 2022-05-17 | 郑州大学 | 一种羧酸还原成醛类化合物的方法 |
| CN114539305A (zh) * | 2022-02-24 | 2022-05-27 | 川北医学院 | 一种通过对苯并呋喃去芳构化制备双键有机化合物的方法 |
| CN114539305B (zh) * | 2022-02-24 | 2023-10-31 | 川北医学院 | 一种通过对苯并呋喃去芳构化制备双键有机化合物的方法 |
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