CN108059598A - 由巴豆酸衍生物制备多取代二烯烃的方法 - Google Patents

由巴豆酸衍生物制备多取代二烯烃的方法 Download PDF

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CN108059598A
CN108059598A CN201610979208.1A CN201610979208A CN108059598A CN 108059598 A CN108059598 A CN 108059598A CN 201610979208 A CN201610979208 A CN 201610979208A CN 108059598 A CN108059598 A CN 108059598A
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虞心红
孙仍蔚
宋伟
章慧文
马春梅
仝岭峰
郑紫薇
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East China University of Science and Technology
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Abstract

本发明公开了一种由巴豆酸衍生物制备多取代二烯烃的方法。本发明涉及一种多取代1,3‑二烯的制备方法。其主要步骤是：在有机溶剂中依次溶入原料I（醛/酮/甲酸酯）,原料II（巴豆酸衍生物）,碱和路易斯酸，适当温度下搅拌反应1~8小时，得到目标产物III（多取代1,3‑二烯）。该方法条件温和，无需惰性气体保护，操作简便，原子利用率高，底物应用范围广阔，适宜工业放大，具有良好的工业化前景。

Description

由巴豆酸衍生物制备多取代二烯烃的方法
技术领域
本发明涉及一种制备多取代二烯烃衍生物的方法，具体地说，涉及一种路易斯酸和有机碱促进的醛(酮)与巴豆酸衍生物发生区域选择性缩合生成多取代二烯烃衍生物的方法。
背景技术
多取代二烯烃作为一种十分重要的合成原料，在Diels-Alder反应，[4+1]环合反应，[4+2] 环合反应以及制备二氢萘环、二氢吲哚、二氢喹啉、二氢苯并呋喃、茚环等过程中有广泛使用[1-12]。
由于二烯烃在合成化学中的重要地位，合成多取代的1,3-二烯方法也受到密切关注。相关方法在综述和论著里有系统的介绍。[13-15]概括地说，合成1,3-二烯的方法包括但不限制于以下种类：有机磷/硫/硅参与的Wittig反应，金属卡宾对α，β-不饱和羰基的烯基化反应，烯烃复分解反应，羟醛缩合及其相关反应，金属介导的C-C生成反应，金属催化的偶联反应，环加成和电环化反应，消除反应，还原反应，非共轭二烯烃的异构反应等。
与本发明最相近的方法是巴豆酸酐与芳香醛发生Perkin反应，得到相应的α-烯基取代肉桂酸。[23]该方法与本发明的区别在于：1).该方法只有酸酐作为原料才能发生反应。而本发明的条件下，巴豆酸、巴豆酸酯酯和巴豆酰胺及其衍生物均可以发生缩合反应。2).该方法需要加热回流的反应条件，而本方法在常温下即可发生反应。3).本发明所用的路易斯酸在反应过程中与巴豆酸衍生物以及醛酮发生配位作用，形成六元环的过渡态，从而实现区域选择性。
Silong Xu等人在2010年报道了通过累积二烯酸酯和醛经三烷基膦催化的反应制备 1,2,3,4-四取代二烯烃，通过换用合适的三烷基膦催化剂可获得可观的立体选择性，收率达 62～99％。[16]
Mathias J.Jacobsen等在2011年报道了一种通过三烷基膦介导的1,3-二烯制备方法，一系列的醛在2-炔-羧酸酯β-发生烯化反应，得到一类1,2,4-三取代的二烯烃。该反应表现出良好的立体选择性，收率最高可达88％。[17]
Marcus M等人在2013年报道了通过烯丙基季磷盐和芳香醛类的Wittig反应来制备一类 1,2,4-三取代的1,3-二烯，收率22～86％。产物具有很好的立体选择性,(E,E)：(E,Z)通常高于98:2。但该方法的局限性在于1,4-取代基只能是芳香环，且其原料要从相应的MBH反应产物卤化经多步制备而得。[18]
JingMei Huang等人在2010年报道了2-炔酸酯与丙烯酸酯/丙烯腈/丙烯酰胺在氯化钯和氯化铜作用下发生氯化-Heck偶联的串联反应制备各种1-氯代的1,3-丁二烯。收率41～82％，产物立体选择性因底物而有变化。[19]
类似地，Sarah J.等人在2010年发表了有机铜试剂和2-炔酸酯“一锅法”氧化偶联制备对称的1,3-二烯衍生物的方法。[20]2009年Barry M.Trost等人报道了2-炔酸酯和烯丙醚在金属钌催化下发生烯炔偶联反应制备1,2,4-三取代1,3-二烯。[21]Atsushi Kinoshita等人报道了钌催化的烯炔复分解反应制备多取代1,3-二烯。[22]
综上，二烯烃由于其在合成化学中的广泛运用，相应的合成方法也得到了密切关注。虽然上述的许多方法有其优势，例如特定的立体选择性，但也表现出很大的局限性。大多数表现为：1).原料不易获得，需要从头制备。2).原子利用率不高，有些反应需要大位阻的有机磷试剂参与3).许多金属催化的反应用到了贵金属，经济性欠佳。4).部分反应需要较为苛刻的强碱、低温、高温等。5).受反应自身约束，只能制备特定类型的产物，不具普适性。
鉴于此，本领域迫切需要发展成本低廉、原料易得、适宜工业放大、应用性广泛的一类新型的制备多取代1,3-二烯的方法。
发明内容
本发明的发明人在现有技术和科研成果的基础上，发现了一种采用成本低廉的路易斯酸和有机碱作为催化剂，采用廉价易得的巴豆酸衍生物和醛发生缩合反应，制备多取代1,3-二烯。该方法在室温下反应，无需惰性气体保护，操作简便，原子利用率高，底物应用范围广阔，适宜工业放大，具有良好的工业化前景。
所述方法的主要步骤是：在非质子有机溶剂中依次溶入原料I,原料II,碱和路易斯酸，必要时可采用冰浴降温。适当温度下搅拌反应1～8小时，得到目标产物III。
式中：
R1为酯基:羧基:或N,N-二取代的酰胺基：
R2，R3分别独立为C1～C5直链或支链烃基，卤代的C1～C5直链或支链烃基，苄基， C6～C10的含取代基的芳基，C4～C10含取代基的芳杂环基，氟，氯，溴，碘中的一种；R2， R3也可以组成C3～C8的环状链烃。所述的取代基为：烷氧基烃基酯基氰基，氟，氯，溴，碘，三氟甲基，取代氨基其中的一种或数种。所述的芳杂环为含氮、氧、磷、硫中的一个或多个的芳香环。
R4，R5为C5～C10的含取代基的芳基，C5～C10含取代基的芳杂环基，氢，烷氧基含季碳的烃基中的一种。所述的取代基为：烷氧基烃基氰基，氟，氯，溴，碘，三氟甲基，取代氨基其中的一种或数种。
R6，R7，R8分别独立选自C5～C10的芳基，C5～C6的芳杂环基，C1～C4的烃基，苄基中的一种。R6，R7也可以是C5～C8的链烃或C5～C8含杂原子O,S,N的链烃。
由于芳香醛、酮、甲酸酯、巴豆酸酯、金属氯化物和叔胺等原料和催化剂均为大宗商业产品，可以预见该方法能够有效控制成本，适宜工业生产。
附图说明
图1是实施例操作通法。
具体实施方式
在本发明的一个优选技术方案中：
优选的催化剂是四氯化钛，优选的碱为三乙胺。
在本发明另一个优选的技术方案中：
优选的非质子溶剂是1,2-二氯乙烷，二氯甲烷。、
下面通过实施例对本发明作进一步说明，其目的仅在于更好的理解本发明的内容。因此，本发明的保护范围不受所举之例的限制。
实施例中的产物结构(含收率与立体选择性)
实施例中的产物结构(含收率与立体选择性)
实施例操作通法
在10mL反应管中依次加入二氯甲烷(8mL)，巴豆酸酯衍生物I(1mmol)，醛/酮/甲酸酯II-a(1mmol,166mg)和三乙胺(3mmol,0.42mL)后将反应放入冰浴中并开启搅拌。5分钟后用移液枪往反应管中滴加四氯化钛(2.0mmol,0.22mL)。TLC跟踪反应进度。反应完成后加水10mL淬灭。分液，水相用少量二氯甲烷萃取三次，合并有机相并用饱和食盐水、清水各洗涤一次。有机相用无水硫酸钠干燥后旋干经硅胶柱柱层析分离(石油醚：乙酸乙酯＝30:1～10:1，V/V)得到黄色油状终产物。
实施例1
Methyl(E)-2-(3,4-dimethoxybenzylidene)but-3-enoate(III-aa)
收率：78％；E/Z:88:12；黄色油状物；
1H NMR(400MHz,Chloroform-d)δ7.45(s,1H),6.98(dd,J＝8.4,2.3Hz,1H),6.94(d,J＝ 2.1Hz,1H),6.80(dd,J＝8.4,2.3Hz,1H),6.66–6.53(m,1H),5.78(d,J＝17.8Hz,1H),5.39 (d,J＝11.6Hz,1H),3.82(s,3H),3.80(s,3H),3.76(s,3H).13C NMR(101MHz,CDCl3)δ 167.8,149.7,148.5,139.4,130.0,128.0,127.8,123.8,120.6,113.0,110.7,55.8,55.8,51.9. HRMS(EI)m/zCalcd for C14H16O4(M):248.1049,found:248.1047
实施例2
Methyl 2-benzylidenebut-3-enoate(III-ab)
收率：72％；E/Z＝91:9；黄色油状物；
Methyl(E)-2-benzylidenebut-3-enoate
1H NMR(400MHz,Chloroform-d)δ7.40(s,1H),7.26(d,J＝7.2Hz,2H),7.23–7.12(m, 3H),6.49(dd,J＝17.6,11.5Hz,1H),5.72(dd,J＝17.6,1.6Hz,1H),5.29(dt,J＝11.5,1.6Hz, 1H),3.68(s,3H).13C NMR(101MHz,CDCl3)δ167.7,139.3,135.2,130.0(2C),129.6,128.7, 128.3,121.0,52.0.HRMS(EI)m/zCalcd for C10H16O2(M):188.0837,found:188.0840
实施例3
Methyl 2-(3,4-dimethylbenzylidene)but-3-enoate(III-ac)
收率：81％；E/Z＝80:20；黄色油状物；
Methyl(E)-2-(3,4-dimethylbenzylidene)but-3-enoate
1H NMR(400MHz,Chloroform-d)δ7.51(s,1H),7.17(d,J＝7.8Hz,2H),7.12(d,J＝7.8Hz, 1H),6.65(ddd,J＝17.7,11.6,1.0Hz,1H),5.85(dd,J＝17.7,1.8Hz,1H),5.42(dt,J＝11.6,1.6 Hz,1H),3.82(s,3H),2.25(s,6H).13C NMR(101MHz,CDCl3)δ168.0,139.8,137.8,136.6, 132.8,131.4,129.9,129.7,127.7,120.5,51.9,19.8,19.7.
Methyl(Z)-2-(3,4-dimethylbenzylidene)but-3-enoate
1H NMR(400MHz,Chloroform-d)δ7.09–7.02(m,3H),6.56(s,1H),6.43(dd,J＝17.5, 10.8Hz,1H),5.33–5.18(m,2H),3.78(s,3H),2.23(s,3H),2.22(s,3H).13C NMR(101MHz, CDCl3)δ169.3,137.3,136.7,135.5,133.4,133.0,132.7,129.9,129.0,125.6,115.8,52.0,19.8, 19.6.HRMS(EI)m/zCalcd for C14H16O2(M):216.1150,found:216.1151
实施例4
Ethyl(E)-2-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)but-3-enoate(III-ad)
收率：84％；E/Z:>99:1；light黄色油状物；
1H NMR(400MHz,Chloroform-d)δ7.43(s,1H),7.00(d,J＝2.0Hz,1H),6.94(dd,J＝8.4,2.0 Hz,1H),6.85(d,J＝8.4Hz,1H),6.64(ddd,J＝17.7,11.7,1.2Hz,1H),5.83(dd,J＝17.7,1.6Hz, 1H),5.44(dt,J＝11.7,1.6Hz,1H),4.34–4.22(m,6H),1.35(t,J＝7.1Hz,3H).13C NMR(101 MHz,CDCl3)δ167.5,144.3,143.2,138.7,129.9,128.8,128.7,124.1,120.6,119.1,117.2,64.5, 64.2,60.8,14.3.HRMS(EI)m/z Calcd for C15H16O4(M):260.1049,found:260.1046
实施例5
Methyl(E)-2-(2-methylbenzylidene)but-3-enoate(III-ae)
收率：78％；E/Z:>99:1；黄色油状物；
1H NMR(400MHz,Chloroform-d)δ7.61(s,1H),7.30–7.10(m,4H),6.46(dd,J＝17.7, 11.5Hz,1H),5.84(dd,J＝17.7,1.6Hz,1H),5.33(dt,J＝11.8,1.6Hz,1H),3.84(s,3H),2.28(s, 3H).13C NMR(101MHz,CDCl3)δ167.6,138.9,137.0,134.4,130.6,130.1,129.7,129.5,128.6, 125.5,120.4,52.0,20.0.HRMS(EI)m/z Calcd for C13H14O2(M):202.0994,found:202.0993
实施例6
Methyl(E)-2-(2-fluorobenzylidene)but-3-enoate(III-af)
收率：66％；E/Z:92:8；黄色油状物；
1H NMR(400MHz,Chloroform-d)δ7.58(s,1H),7.42(td,J＝7.5,1.7Hz,1H),7.32(qd,J＝7.7,5.4,1.7Hz,1H),7.16–7.04(m,2H),6.55(dd,J＝17.7,11.6Hz,1H),5.88(dd,J＝17.7, 1.6Hz,1H),5.44(dt,J＝11.6,1.6Hz,1H),3.85(s,3H).13C NMR(101MHz,Chloroform-d)δ 167.3,160.5(d,J＝250.7Hz),131.8(d,J＝4.1Hz),131.7,131.2(d,J＝2.9Hz),130.6(d,J＝8.6 Hz),129.4,123.8(d,J＝3.6Hz),123.1(d,J＝14.0Hz),121.5,115.7(d,J＝21.4Hz), 52.1.HRMS(EI)m/zCalcd for C12H11FO2(M):206.0743,found:206.0742
实施例7
Methyl(E)-2-(2-chlorobenzylidene)but-3-enoate(III-ag)
收率：78％；E/Z>99:1；黄色油状物；
1H NMR(400MHz,Chloroform-d)δ7.60(dd,J＝8.0,1.2Hz,1H),7.55(s,1H),7.34(dd,J＝ 7.6,1.9Hz,1H),7.29(td,J＝7.5,1.2Hz,1H),7.17(td,J＝7.7,1.9Hz,1H),6.45(dd,J＝17.7, 11.6Hz,1H),5.87(dd,J＝17.6,1.9Hz,1H),5.39(dt,J＝11.6,1.6Hz,1H),3.86(s,3H).13C NMR(101MHz,CDCl3)δ167.2,138.3,135.5,132.8,131.5,131.3,130.0,129.1,127.0,124.3, 121.5,52.2.HRMS(EI)m/zCalcd for C12H11ClO2(M):222.0448,found:222.0451
实施例8
Methyl(E)-2-(2-bromobenzylidene)but-3-enoate(III-ah)
收率：79％；E/Z>99:1；黄色油状物；
1H NMR(400MHz,Chloroform-d)δ7.60(d,J＝7.7Hz,1H),7.55(s,1H),7.34(dd,J＝7.7, 1.8Hz,1H),7.29(t,J＝7.7Hz,1H),7.17(td,J＝7.7,1.8Hz,1H),6.45(dd,J＝17.7,11.6Hz,1H), 5.87(dd,J＝17.7,1.6Hz,1H),5.40(dt,J＝11.6,1.6Hz,1H),3.86(s,3H).13C NMR(101MHz, CDCl3)δ167.2,138.3,135.5,132.8,131.4,131.3,130.0,129.1,127.0,124.3,121.5,52.1. HRMS(EI)m/z Calcd for C12H11BrO2(M):265.9942,found:265.9945
实施例9
Methyl(E)-2-(2-nitrobenzylidene)but-3-enoate(III-ai)
收率：88％；E/Z:>99:1；yellow solid；
1H NMR(400MHz,Chloroform-d)δ8.16(d,J＝8.2Hz,1H),7.80(s,1H),7.67(t,J＝7.5Hz, 1H),7.54(t,J＝7.7Hz,1H),7.43(d,J＝7.7Hz,1H),6.34(dd,J＝17.6,11.5Hz,1H),5.79(dd,J ＝17.6,1.6Hz,1H),5.35(dt,J＝11.5,1.5Hz,1H),3.87(s,3H).13C NMR(101MHz,CDCl3)δ166.8,147.6,135.9,133.4,132.1,131.4,131.3,129.3,128.6,124.9,122.0,52.2.HRMS(EI)m/z Calcd for C12H11NO4(M):233.0688,found:233.0685
实施例10
Methyl(E)-2-(4-cyanobenzylidene)but-3-enoate(III-aj)
收率：44％(incomplete conversion,c.a.40％startingmaterial recovered)；E/Z:>99:1；light黄色油状物；
1H NMR(400MHz,Chloroform-d)δ7.60(d,J＝8.4Hz,2H),7.44(d,J＝8.4Hz,2H),7.41(s, 1H),6.47(dd,J＝17.5,11.5Hz,1H),5.80(d,J＝17.6Hz,1H),5.43(d,J＝11.6Hz,1H),3.79(s, 3H).13C NMR(101MHz,CDCl3)δ167.0,139.7,136.5,132.6(2C),132.0(2C),130.4,128.7, 122.8,118.4,111.9,52.3.HRMS(EI)m/zCalcd for C13H11NO2(M):213.0790,found:213.0791
实施例11
Methyl(E)-2-(4-(dimethylamino)benzylidene)but-3-enoate(III-ak)
收率：70％；E/Z:96:4；黄色油状物；
1H NMR(400MHz,Chloroform-d)δ7.31(d,J＝8.9Hz,2H),6.60(ddd,J＝17.7,11.6,1.1Hz, 1H),6.57(d,J＝8.9Hz,2H),5.72(dd,J＝17.7,2.0Hz,1H),5.33(dt,J＝11.6,1.6Hz,1H),3.71 (s,3H),2.89(s,6H).13C NMR(101MHz,CDCl3)δ168.3,150.7,140.6,132.2(2C),130.7,125.0, 122.9,119.5,111.5(2C),51.8,40.1.HRMS(EI)m/z Calcd forC14H17NO2(M):231.1259,found: 231.1258
实施例12
Methyl-2-(3-fluorobenzylidene)but-3-enoate(III-al)
Methyl(E)-2-(3-fluorobenzylidene)but-3-enoate
收率：59％；E/Z:83:17；黄色油状物；
1H NMR(400MHz,Chloroform-d)δ7.47(s,1H),7.37–7.30(m,1H),7.20–7.16(m,1H), 7.16–7.10(m,1H),7.05–6.98(m,1H),6.59(ddd,J＝17.8,11.7,1.1Hz,1H),5.85(dd,J＝17.8,1.7Hz,1H),5.47(dt,J＝11.7,1.6Hz,1H),3.85(s,3H).
13C NMR(101MHz,Chloroform-d)δ167.5,162.5(d,J＝246.4Hz),137.6(d,J＝2.3Hz), 137.3(d,J＝7.9Hz),131.2,129.9(d,J＝8.6Hz),129.2,125.8(d,J＝2.9Hz),121.8,116.6(d,J＝ 22.1Hz),115.6(d,J＝21.3Hz),52.1.
Methyl(Z)-2-(3-fluorobenzylidene)but-3-enoate
1H NMR(400MHz,Chloroform-d)δ7.31–7.21(m,1H),7.19(s,1H),7.17–7.09(m,1H), 7.00–6.94(m,1H),6.59(s,1H),6.45(dd,J＝17.5,10.8Hz,1H),5.40–5.26(m,2H),3.79(s, 3H).(some signals are incorporated with E isomer,not available.)13CNMR(101MHz, Chloroform-d)δ168.6,162.7(d,J＝245.8Hz),137.3(d,J＝6.5Hz),135.2,134.9,131.6(d,J ＝2.3Hz),130.0(d,J＝8.9Hz),124.0(d,J＝2.9Hz),117.4,115.3(d,J＝21.3Hz),114.7(d,J＝ 22.1Hz),52.2.HRMS(EI)m/zCalcd for C12H11FO2(M):206.0743,found:206.0741
实施例13
Ethyl(E)-2-(naphthalen-1-ylmethylene)but-3-enoate(III-bm)
收率：87％；E/Z:94:6；黄色油状物；
1H NMR(400MHz,Chloroform-d)δ8.04(s,1H),7.97–7.90(m,1H),7.90–7.79(m,2H), 7.55–7.41(m,4H),6.50(dd,J＝17.7,11.6Hz,1H),5.89(dd,J＝17.7,1.8Hz,1H),5.32(dt,J ＝11.6,1.6Hz,1H),4.38(q,J＝7.1Hz,2H),1.41(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3) δ167.3,137.6,133.5,132.5,132.3,131.6,129.8,129.0,128.6,127.8,126.5,126.2,125.1,124.8, 120.5,61.1,14.4.HRMS(EI)m/z Calcd for C13H14O2(M):252.1150,found:252.1151
实施例14
Methyl 2-((5-bromofuran-2-yl)methylene)but-3-enoate(III-an)
收率：70％；E/Z:67:33；light黄色油状物；
Methyl(E)-2-((5-bromofuran-2-yl)methylene)but-3-enoate
1H NMR(400MHz,Chloroform-d)δ7.14(s,1H),6.99(ddd,J＝17.5,11.6,1.0Hz,1H),6.60 (d,J＝3.5Hz,1H),6.41(d,J＝3.6Hz,1H),5.97(dd,J＝17.6,1.9Hz,1H),5.52(dt,J＝11.7,1.5 Hz,1H),3.81(s,3H).13C NMR(101MHz,CDCl3)δ167.2,153.3,134.3,129.4,125.4,124.0, 121.5,118.3,114.2,52.0.
Methyl(Z)-2-((5-bromofuran-2-yl)methylene)but-3-enoate
1H NMR(400MHz,Chloroform-d)δ6.43(d,J＝3.4Hz,1H),6.39–6.31(m,2H),6.28(s, 1H),5.39–5.20(m,2H),3.90(s,3H).13C NMR(101MHz,CDCl3)δ168.1,152.2,131.2,126.1,123.7,118.3,117.1,114.7,113.7,52.2.HRMS(EI)m/zCalcd for C10H9BrO3(M):255.9735, found:255.9732
实施例15
Methyl-2-(thiophen-2-ylmethylene)but-3-enoate(III-ao)
收率：95％；E/Z:67:33；light黄色油状物；
Methyl(E)-2-(thiophen-2-ylmethylene)but-3-enoate
1H NMR(400MHz,Chloroform-d)δ7.64(s,1H),7.38(d,J＝5.1Hz,1H),7.21(d,J＝3.7Hz, 1H),6.99(dd,J＝5.1,3.7Hz,1H),6.71(ddd,J＝17.4,11.5,1.2Hz,1H),5.82(dd,J＝17.5,1.7 Hz,1H),5.50(dt,J＝11.6,1.4Hz,1H),3.74(s,3H).
Methyl(Z)-2-(thiophen-2-ylmethylene)but-3-enoate
1H NMR(400MHz,Chloroform-d)δ6.43(d,J＝3.4Hz,1H),6.39–6.31(m,2H),6.28(s, 1H),5.39–5.20(m,2H),3.90(s,3H).13C NMR(101MHz,CDCl3)δ168.1,152.2,131.2,126.1,123.7,118.3,117.1,114.7,113.7,52.2.
HRMS(EI)m/zCalcd for C10H10O2S(M):194.0402,found:194.0405
实施例16
Ethyl-2-(benzo[b]thiophen-5-ylmethylene)but-3-enoate(III-bp)
收率：73％；E/Z:83:17；brown solid；
Ethyl(E)-2-(benzo[b]thiophen-5-ylmethylene)but-3-enoate
1H NMR(400MHz,Chloroform-d)δ7.92–7.81(m,2H),7.74(s,1H),7.62(s,1H),7.45–7.38(m,2H),6.73(dd,J＝17.7,11.6Hz,1H),5.94(dd,J＝17.7,1.5Hz,1H),5.47(dt,J＝11.7, 1.5Hz,1H),4.35(q,J＝7.1Hz,2H),1.40(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ 167.2,139.5,138.5,131.4,130.9,130.6,130.2,128.5,124.9,124.6,122.7,122.1,121.1,61.1,14.3.
Ethyl(Z)-2-(benzo[b]thiophen-5-ylmethylene)but-3-enoate
1H NMR(400MHz,Chloroform-d)δ7.83(d,J＝7.9Hz,1H,incorporated),7.79(d,J＝7.9Hz, 1H),7.55(s,1H),7.45(s,1H),7.40–7.32(m,1H),6.86(s,1H),6.56(dd,J＝17.5,10.8Hz,1H), 5.42–5.28(m,2H),4.25(q,J＝7.1Hz,2H),1.18(t,J＝7.1Hz,3H).13CNMR(101MHz, CDCl3)δ168.5,139.5,138.4,135.6,135.0,130.6,125.0,124.7,124.4,124.3,122.7,121.6, 116.9,61.3,14.0.HRMS(EI)m/z Calcd for C15H14O2S(M):258.0715,found:258.0711
实施例17
Methyl(E)-2-((benzyloxy)methylene)but-3-enoate(III-aq)
收率：64％；E/Z:>99:1；colorless oil；
1H NMR(400MHz,Chloroform-d)δ7.43(s,1H),7.32–7.16(m,5H),6.47(dd,J＝17.9, 11.9Hz,1H),5.82(dd,J＝17.9,2.3Hz,1H),5.16(ddd,J＝11.9,2.3,1.2Hz,1H),4.93(s,2H), 3.57(s,3H).13C NMR(101MHz,CDCl3)δ167.6,158.8,135.9,128.8(2C),128.6,127.4(2C), 126.7,117.1,109.1,76.6,51.3.HRMS(EI)m/z Calcd for C13H14O3(M):218.0943,found: 318.0945
实施例18
Methyl(E)-2-(ethoxymethylene)but-3-enoate(III-ar)
收率：45％；E/Z:>99:1；colorless oil；
1H NMR(400MHz,Chloroform-d)δ7.40(s,1H),6.44(dd,J＝17.9,11.9Hz,1H),5.79(dd,J＝ 17.9,2.5Hz,1H),5.16(ddd,J＝11.9,2.5,1.2Hz,1H),4.05(q,J＝7.1Hz,2H),3.64(s,3H),1.29 (t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ167.8,159.1,126.7,116.4,108.2,71.1,51.2, 15.3.HRMS(EI)m/z Calcd for C8H12O3(M):156.0786,found:156.0784
实施例19
Methyl(2E,4E)-5-(m-tolyl)-2-vinylpenta-2,4-dienoate(III-as)
收率：33％(incomplete conversion,c.a.30％startingmaterial recovered)；E/Z:>99:1；黄色油状物；
1H NMR(400MHz,Chloroform-d)δ7.45–7.31(m,1H),7.31–7.19(m,5H),7.11(d,J＝ 7.2Hz,2H),6.90(d,J＝15.0Hz,1H),6.69(dd,J＝17.6,11.5Hz,1H),5.70(dd,J＝17.6,1.9Hz, 1H),5.49(dd,J＝11.5,1.9Hz,1H),3.80(s,3H),2.36(s,3H).13C NMR(101MHz,CDCl3)δ 167.6,140.7,139.6,138.4,136.4,129.8,129.6,128.7,128.5,127.9,124.5,123.6,120.6,51.9,21.4. HRMS(EI)m/z Calcd for C15H16O2(M):228.1150,found:228.1153
实施例20
Methyl(2E,4E)-5-(4-nitrophenyl)-2-vinylpenta-2,4-dienoate(III-at)
收率：39％(incomplete conversion,c.a.40％starting material recovered)；E/Z:>99:1；brown oil；
1H NMR(400MHz,Chloroform-d)δ8.21(d,J＝8.8Hz,2H),7.60(d,J＝8.8Hz,2H),7.46– 7.31(m,2H),6.96(d,J＝14.4Hz,1H),6.69(dd,J＝17.5,11.5Hz,1H),5.71(dd,J＝17.5,1.7Hz, 1H),5.57(ddd,J＝11.5,1.7,0.8Hz,1H),3.83(s,3H).13C NMR(101MHz,CDCl3)δ167.2, 142.7,137.8,137.1,133.4,131.8,129.4,128.0,127.6(2C),124.2(2C),121.9,52.2.HRMS(EI)m/z Calcd for C14H13NO4(M):259.0845,found:259.0848
实施例21
4-ethyl 1-methyl 2-vinylmaleate(III-au)
E/Z configuration matches reference.3
收率：48％；E/Z:13:87；yellow solid；
1H NMR(400MHz,Chloroform-d)δ6.33(dd,J＝17.5,10.7Hz,1H),5.81(s,1H),5.55– 5.40(m,2H),4.13(q,J＝7.2Hz,2H),3.83(s,3H),1.21(t,J＝7.2Hz,5H).13C NMR(101MHz, CDCl3)δ167.4,164.9,147.3,132.8,123.7,120.3,60.9,52.5,14.1.HRMS(EI)m/zCalcd for C9H12O4(M):184.0736,found:184.0733
实施例22
Methyl-4,4-dimethyl-2-vinylpent-2-enoate(III-av)
收率：52％；E/Z＝89:11；light黄色油状物；
1H NMR(400MHz,Chloroform-d)δ6.69–6.59(m,2H),5.50(dd,J＝17.7,1.8Hz,1H), 5.35(dt,J＝11.5,1.5Hz,1H),3.75(s,3H),1.20(s,9H).13C NMR(101MHz,CDCl3)δ168.6, 151.8,129.7,129.5,119.5,51.9,33.6,30.6(3C).HRMS(EI)m/zCalcd for C10H16O2(M):168.1150, found:168.1152
实施例23
Ethyl(E)-2-(3,4-dimethoxybenzylidene)-3-methylbut-3-enoate(3ca)
Yield:77％；E/Z:91:9；light yellow oil；
1H NMR(400MHz,Chloroform-d)δ7.51(s,1H),7.35(d,J＝2.1Hz,1H),7.19(dd,J＝8.4, 2.1Hz,1H),6.84(d,J＝8.4Hz,1H),5.27(p,J＝1.6Hz,1H),4.99(dd,J＝2.0,1.1Hz,1H),4.27 (q,J＝7.1Hz,2H),3.90(s,3H),3.85(s,3H),2.02(t,J＝1.6Hz,3H),1.34(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ167.5,149.9,148.4,141.3,138.0,131.9,127.6,124.6,117.0,112.4, 110.6,60.9,55.8,55.6,22.7,14.3.HRMS(EI)m/zCalcd forC16H20O4(M):276.1362,found: 276.1364
实施例24
Ethyl(E)-2-(3,4-dimethoxybenzylidene)-3-phenylbut-3-enoate(3da)
Yield:39％；E/Z:>99:1；light yellow oil；
1H NMR(400MHz,Chloroform-d)δ7.82(s,1H),7.61–7.44(m,2H),7.37–7.22(m,3H), 7.22(d,J＝2.1Hz,1H),7.17(dd,J＝8.4,2.1Hz,1H),6.77(d,J＝8.4Hz,1H),5.90(s,1H),5.29 (s,1H),4.17(q,J＝7.1Hz,2H),3.85(s,3H),3.61(s,3H),1.17(t,J＝7.1Hz,3H).13C NMR(101 MHz,CDCl3)δ167.7,150.1,148.3,143.8,140.6,138.4,129.9,128.6(2C),128.0,127.3, 125.7(2C),124.9,115.9,112.6,110.6,60.9,55.8,55.5,14.1.HRMS(EI)m/zCalcd for C21H22O4 (M):338.1518,found:338.1521
实施例25
(E)-diethyl 2-(3,4-dimethoxybenzylidene)-3-methylenesuccinate(3ea)
Yield:91％；E/Z:>99:1；light yellow solid；
1H NMR(400MHz,Chloroform-d)δ7.74(s,1H),7.07(dd,J＝8.3,2.1Hz,1H),7.04(d,J＝ 2.1Hz,1H),6.83(d,J＝8.3Hz,1H),6.54(d,J＝1.5Hz,1H),5.73(d,J＝1.5Hz,1H),4.26(q,J＝ 7.1Hz,2H),4.20(q,J＝7.1Hz,2H),3.89(s,3H),3.82(s,3H),1.31(t,J＝7.1Hz,3H),1.21(t,J＝ 7.1Hz,3H).13C NMR(101MHz,CDCl3)δ166.9,166.1,150.1,148.5,141.2,136.9,130.0, 127.2,126.4,124.4,112.5,110.8,61.0,55.8,55.7,14.2,14.1.HRMS(EI)m/zCalcd for C18H22O6 (M):334.1416,found:334.1413
实施例26
(E)-ethyl 2-(cyclopent-1-en-1-yl)-3-(3,4-dimethoxyphenyl)acrylate(3fa)
Yield:48％；E/Z:>99:1；light yellow oil；
1H NMR(400MHz,Chloroform-d)δ7.55(s,1H),7.25(d,J＝2.0Hz,1H),7.07(dd,J＝8.4, 2.0Hz,1H),6.82(d,J＝8.4Hz,1H),5.72(p,J＝2.1Hz,1H),4.25(q,J＝7.1Hz,2H),3.88(s, 3H),3.84(s,3H),2.59–2.44(m,4H),2.02(p,J＝7.6Hz,2H),1.32(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ167.7,149.8,148.4,138.8,131.3,128.1,127.8,124.5,111.9,110.6, 60.7,55.8,55.5,35.5,33.3,23.7,14.3.HRMS(EI)m/zCalcd for C18H22O4(M):302.1518,found: 302.1520
实施例27
(E)-ethyl 2-(cyclohex-1-en-1-yl)-3-(3,4-dimethoxyphenyl)acrylate(3ga)
Yield:58％；E/Z:>99:1；light yellow oil；
1H NMR(400MHz,Chloroform-d)δ7.47(s,1H),7.38(d,J＝1.9Hz,1H),7.12(dd,J＝8.4, 1.9Hz,1H),6.83(d,J＝8.4Hz,1H),5.67(dt,J＝4.0,2.0Hz,1H),4.24(q,J＝7.1Hz,2H),3.90 (s,3H),3.88(s,3H),2.26–2.06(m,4H),1.84–1.63(m,4H),1.33(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ168.1,149.8,148.4,137.8,133.9,132.7,128.1,127.7,124.8,111.9, 110.6,60.7,55.8,55.8,28.2,25.5,23.0,22.0,14.3.HRMS(EI)m/zCalcd for C19H24O4(M): 316.1675,found:316.1673
实施例28
(E)-ethyl 2-(cyclohept-1-en-1-yl)-3-(3,4-dimethoxyphenyl)acrylate(3ha)
Yield:52％；E/Z:>99:1；light yellow oil；
1H NMR(400MHz,Chloroform-d)δ7.41(s,1H),7.28(d,J＝2.1Hz,1H),7.12(dd,J＝8.3, 2.1Hz,1H),6.82(d,J＝8.3Hz,1H),5.80(t,J＝6.2Hz,1H),4.24(q,J＝7.1Hz,3H),3.88(s,6H), 2.40–2.28(m,2H),2.27–2.14(m,2H),1.87–1.70(m,4H),1.61(p,J＝5.5Hz,2H),1.34 (t,J＝7.2Hz,3H).13C NMR(101MHz,CDCl3)δ168.3,149.7,148.3,139.2,136.7,134.8, 132.7,128.2,124.5,112.3,110.6,60.7,55.8(2C),34.1,32.3,29.3,26.8,26.7,14.3.HRMS(EI) m/zCalcd for C20H26O4(M):330.1831,found:330.1832
实施例29
Ethyl(E)-2-((E)-3,4-dimethoxybenzylidene)-3-methyl-4-phenylbut-3-enoate(3ja)
Yield:72％；E/Z:>99:1；yellow solid；
1H NMR(400MHz,Chloroform-d)δ7.68(d,J＝1.3Hz,1H),7.58–7.49(m,2H),7.40–7.31(m,2H),7.30–7.27(m,2H),7.15(dd,J＝8.4,2.0Hz,1H),6.82(d,J＝8.4Hz,1H),6.66–6.60(m,1H),4.28(q,J＝7.1Hz,2H),3.87(s,3H),3.67(s,3H),1.88(d,J＝1.3Hz,3H),1.33 (t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ168.1,149.9,148.6,142.3,139.7,139.5, 128.5,128.4(2C),127.5,126.8,125.7(2C),124.6,121.8,112.1,110.8,60.9,55.8,55.6,17.6,14.4. HRMS(EI)m/zCalcd for C22H24O4(M):352.1675,found:352.1677
实施例30
{422}Ethyl(E)-2-((E)-3,4-dimethoxybenzylidene)-4-phenylbut-3-enoate(3ka)
1H NMR(400MHz,Chloroform-d)δ7.56(s,1H),7.46–7.38(m, 2H),7.34–7.29(m,2H),7.27(d,J＝5.9Hz,1H),7.25–7.15(m,1H),7.10(dd,J＝16.5,1.1 Hz,1H),7.09–7.01(m,2H),6.86(d,J＝8.2Hz,1H),4.33(q,J＝7.1Hz,2H),3.87(s,3H), 3.78(s,3H),1.38(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ167.4,149.8,148.7,139.0, 137.6,134.3,128.7(2C),128.4,128.2,127.8,126.5(2C),124.0,122.1,113.1,111.0,60.9,55.9, 55.8,14.4.HRMS(EI)m/zCalcd for C21H22O4(M):338.1518,found:338.1521
实施例31
(2E,3E)-ethyl 2-(3,4-dimethoxybenzylidene)hex-3-enoate(3la)
Yield:85％；E/Z:>99:1；light yellow oil；
1H NMR(400MHz,Chloroform-d)δ7.37(s,1H),7.09–7.01(m,2H),6.87(d,J＝8.9Hz, 1H),6.36–6.32(m,1H),6.34(s,1H),4.29(q,J＝7.1Hz,2H),3.90(s,3H),3.87(s,3H),2.21 (qdd,J＝7.4,3.4,1.4Hz,2H),1.36(t,J＝7.1Hz,3H),1.07(d,J＝7.4Hz,3H).13CNMR(101 MHz,CDCl3)δ167.9,149.3,148.4,138.9,136.8,128.6,128.4,123.6,122.1,112.9,110.7,60.7, 55.8,55.7,26.6,14.2,13.2.HRMS(EI)m/zCalcd for C17H22O4(M):290.1518,found:290.1519
实施例32
Methyl-2-(-3,4-dimethoxybenzylidene)hex-3-enoate(3ma)
Yield:58％；E/Z:60:40；light yellow oil；
Methyl(E)-2-((E)-3,4-dimethoxybenzylidene)hex-3-enoate
1H NMR(400MHz,Chloroform-d)δ7.59(s,1H),7.29(d,J＝2.0Hz,1H),7.18(dd,J＝8.4, 2.0Hz,1H),6.85(d,J＝8.4Hz,1H),6.16(dd,J＝11.2,1.8Hz,1H),5.74(dt,J＝11.2,7.5Hz, 1H),3.90(s,3H),3.85(s,3H),3.81(s,3H),1.87(pd,J＝7.5,1.6Hz,2H),0.88(t,J＝7.5Hz,3H). 13C NMR(101MHz,CDCl3)δ168.7,149.9,148.4,139.7,137.5,128.3,125.7,124.6,122.7, 112.7,110.6,55.8,55.8,52.2,22.8,13.2.
实施例33
Methyl(E)-2-((Z)-3,4-dimethoxybenzylidene)hex-3-enoate
1H NMR(400MHz,Chloroform-d)δ7.39(s,1H),7.12–7.01(m,2H),6.88(d,J＝8.9Hz, 1H),6.35–6.30(m,2H),3.91(s,3H),3.88(s,3H),3.83(s,3H),2.30–2.14(m,2H),1.06(t, J＝7.4Hz,3H).
13C NMR(101MHz,CDCl3)δ168.5,149.4,148.4,139.1,137.3,128.4,128.3,123.7,122.0, 112.9,110.7,55.9,55.8,52.0,26.6,13.3.HRMS(EI)m/zCalcd for C16H20O4(M):276.1362,found: 276.1364
实施例34
Ethyl(Z)-4-bromo-2-((E)-3,4-dimethoxybenzylidene)but-3-enoate(3na)
Yield:47％；E/Z:>99:1；yellow oil；
1H NMR(400MHz,Chloroform-d)δ7.66(d,J＝1.6Hz,1H),7.19–7.11(m,2H),7.02(dd, J＝7.7,1.7Hz,1H),6.86(d,J＝8.2Hz,1H),6.61(d,J＝8.2Hz,1H),4.29(q,J＝7.1Hz,2H), 3.90(s,3H),3.86(s,3H),1.34(t,J＝7.1Hz,3H).13C NMR(101MHz,CDCl3)δ166.5,150.3, 148.6,141.1,129.4,127.6,124.7,124.5,113.1,112.8,110.8,61.2,55.9,55.8,14.3.HRMS(EI) m/zCalcd for C15H17BrO4(M):340.0310,found:340.0314
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Claims (10)

1.由巴豆酸衍生物制备多取代二烯烃的方法
一种制备式III所示化合物的方法，其特征在于，所述方法的主要步骤是：在有机碱及路易斯酸存在的条件下，由式I所示化合物与式II所示化合物在非质子有机溶剂中于 －30℃ ～ 90 ℃的温度下发生缩合反应，得到目标物III；其中I,II,III的结构如下：
式中：R1 为酯基: ，羧基: ,或N,N-二取代的酰胺基：；R2，R3分别独立为C1~C5直链或支链烃基，卤代的C1~C5直链或支链烃基，苄基 ，C6~C10的含取代基的芳基，C4~C10含取代基的芳杂环基，氟，氯，溴，碘中的一种；R2 ，R3也可以组成C3~C8的环状链烃；所述的取代基为：烷氧基，烃基，酯基，氰基，氟，氯，溴，碘，三氟甲基，取代氨基， 其中的一种或数种；所述的芳杂环为含 氮、氧、磷、硫中的一个或多个的芳香环；R4，R5为C5~C10的含取代基的芳基，C5~C10含取代基的芳杂环基，氢，烷氧基，含季碳的烃基，中的一种；所述的取代基为：烷氧基，烃基，氰基，氟，氯，溴，碘，三氟甲基，取代氨基， 其中的一种或数种；R6，R7，R8分别独立选自C5~C10的芳基，C5~C6的芳杂环基，C1~C4的烃基，苄基中的一种；R6，R7 也可以是C5~C8 的链烃或C5~C8 含杂原子O,S,N的链烃。
2. 如权利要求1所述的方法，其特征在于: R1 为酯基: ，羧基: ；R2，R3分别独立为C1~C5直链或支链烃基，苄基，C6~C10的含取代基的芳基，C4~C10含取代基的芳杂环基，氟，氯，溴，碘中的一种；R2 ，R3也可以组成C4~C8的环状链烃；所述的取代基为：烷氧基，烃基，氰基，氟，氯，溴，碘，三氟甲基，取代氨基， 其中的一种或数种；所述的芳杂环为含 氮、氧、磷、硫中的一个或多个的芳香环；R4，R5为C5~C10的含取代基的芳基，C5~C10含取代基的芳杂环基，氢，烷氧基，含季碳的烃基，中的一种；所述的取代基为：烷氧基，烃基，氰基，氟，氯，溴，碘，三氟甲基，取代氨基， 其中的一种或数种；R6，R7，R8分别独立选自甲基，乙基，正丙基，异丙基，正丁基，叔丁基，苄基，苯氧基中的一种。
3. 如权利要求2所述的方法，其特征在于: R1 为酯基: ；R2 ，R3分别独立为C1~C4直链或支链烃基，苄基，含取代基的苯环、萘环、呋喃、噻吩，吲哚，苯并呋喃；R2 ，R3也可以组成C4~C8的环状链烃；所述的取代基为：烷氧基，烃基，氰基，氟，氯，溴，三氟甲基，取代氨基， 其中的一种或数种；所述的芳杂环为含 氮、氧、磷、硫中的一个或多个的芳香环；R4，R5为C5~C10的含取代基的芳基，C5~C10含取代基的芳杂环基，氢，烷氧基，含季碳的烃基，中的一种；所述的取代基为：烷氧基，烃基，氰基，氟，氯，溴，碘，三氟甲基，取代氨基， 其中的一种或数种；R6，R7，R8分别独立选自甲基，乙基，正丙基，异丙基，苄基，苯氧基中的一种。
4. 如权利要求1中所述的方法，其中R1 为酯基: ，R2 ，R3分别独立为C1~C4直链或支链烃基，苄基，含取代基的苯环、萘环、呋喃、噻吩，吲哚，苯并呋喃；R2 ，R3也可以组成C4~C8的环状链烃；所述的取代基为：烷氧基，烃基，氰基，氟，氯，溴，三氟甲基，取代氨基， 其中的一种或数种；R4为H, R5为烷氧基 ；R6，选自甲基，乙基，正丙基，异丙基，苄基，苯氧基中的一种。
5. 如权利要求1所述的方法，其特征在于:所述的有机碱为三甲胺，三乙胺，三正丙胺，三正丁胺， 二异丙基乙基胺，二乙基苯胺，二甲基苯胺，三甲胺，三乙烯二胺中的一种；所述的路易斯酸为铝，铁，铜，钛，锌，锡等6种金属的卤化物、硝酸盐、硫酸盐中的一种或数种的混合物。
6. 如权利要求1所述的方法，其特征在于:所述的非质子有机溶剂为 二氯甲烷，二氯乙烷，氯仿，四氯化碳，氯苯，甲苯，二甲苯，四氢呋喃，乙醚，乙腈中的一种或其中数种的混合；溶剂中所含溶质量为0.05~2.0摩尔/升。
7. 如权利要求5所述的路易斯酸，优选的路易斯酸为 四氯化钛，四溴化钛，三氯化铝。
8. 如权利要求1~7中任意一项所述的方法，其特征在于反应的温度范围为－10℃~ 40℃。
9. 如权利要求1~7中任意一项所述的方法，其原料I:原料II:路易斯酸:碱的用量（摩尔量）比例为 1.0:0.5~2.0:0.5~4.0:1.0~10.0。
10. 如权利要求1~7中任意一项所述的方法，其优选的原料I:原料II:路易斯酸:碱比例为 1.0:0.9~1.1:1.5~2.5:3.0~4.0。
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Application publication date: 20180522