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CN114805069B - 一种由末端烯烃合成α二氟代酯类衍生物的方法 - Google Patents

一种由末端烯烃合成α二氟代酯类衍生物的方法 Download PDF

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CN114805069B
CN114805069B CN202210465515.3A CN202210465515A CN114805069B CN 114805069 B CN114805069 B CN 114805069B CN 202210465515 A CN202210465515 A CN 202210465515A CN 114805069 B CN114805069 B CN 114805069B
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芦逵
苏俊奇
刘瑞月
张颖
周宁宁
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Tianjin University of Science and Technology
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Abstract

本发明涉及有机合成领域，涉及一种由末端烯烃合成α二氟代酯类衍生物的方法，利用[双(2‑(乙氧羰基)‑2,2‑二氟乙酰氧基)碘]苯作为二氟乙酸乙酯自由基前体，在可见光催化下，产生二氟乙酸乙酯基自由基，随后与末端烯烃发生自由基加成反应，得到α二氟代酯类衍生物。具体是在反应管中将末端烯烃、[双(2‑(乙氧羰基)‑2,2‑二氟乙酰氧基)碘]苯用THF溶解，在蓝色12WLED灯照下室温反应，合成一系列加成的二氟烷烃产物。本发明采用便宜易得的[双(2‑(乙氧羰基)‑2,2‑二氟乙酰氧基)碘]苯作为二氟烷基源，在无光催化剂的作用下，从末端烯烃制备了α二氟代酯类衍生物，合成方法简便快捷，操作也很方便。

Description

一种由末端烯烃合成α二氟代酯类衍生物的方法
技术领域
本发明属于有机合成领域，涉及一种由[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯作为二氟乙酸乙酯自由基来源，在光催化由末端烯烃得到α二氟代酯类衍生物的方法。
背景技术
将氟原子或者含氟基团引入有机小分子中，能够显著性地改善分子的亲脂性，脂溶性，代谢稳定性，细胞通透性等性质。另一方面，氟被广泛地认为是氢原子的一种代谢稳定的类似物和(或)替代物，因此，超过20％的药品和30％的农用化学品至少有一个氟原子。氟取代对药物分子的物理和化学性质有重大影响，因此将二氟烷基化基团结合到有机化合物中是特别有利的。
在国内外许多课题组已经成功制备出二氟乙酸乙酯自由基前体参加反应。采用的二氟乙酸乙酯自由基前体有二氟溴乙酸乙酯、二氟碘乙酸乙酯、二氟铜乙酸乙酯、二氟苯基硒基乙酸乙酯、二氟甲基亚磺酸锌、二氟甲基亚磺酸钠、二氟甲基膦盐等。这些二氟乙酸乙酯化试剂中有一些已经能够可以工业化生产，但是反应过程中需要用到氧化剂、昂贵的金属催化剂，或者二氟烷基化试剂本身合成比较困难。1996年Burton报道以铜粉为催化剂用二氟碘乙酸乙酯作为二氟乙酸乙酯化试剂实现了对烯烃的二氟乙酸乙酯化反应。后来Kumadaki教授、ltoh教授、卿凤翎教授等课题组对二氟乙酸乙酯化试剂进行了优化和创新。
目前合成末端二氟乙酸乙酯基加成合成烷烃产物的方法包括：1)烯烃和二氟碘乙酸乙酯在铜的催化下，溶液升温至70℃得到。该方法的缺点是需要用到金属催化剂，而且反应过程中需要升温；2)通过二氟溴乙酸乙酯，在fac-Ir(ppy)3的催化下，在蓝光LED灯的照射下与烯烃反应来制备。该方法的缺点是需要使用昂贵的金属光催化剂；3)由二氟氟磺酰基乙酸甲酯与烯烃反应，该方法的缺点是需要使用昂贵的金属光催化剂。
发明内容
本发明的目的是由[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯作为二氟乙酸乙酯基自由基前体与末端烯烃反应从而生成二α二氟代酯类衍生物的方法。
具体步骤：在无水无氧条件下加入烯烃、[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯和四氢呋喃，在蓝色12W LED灯光照下室温反应。反应结束后，经萃取，洗涤，干燥，柱层析分离得到加成的二氟烷烃产物。
所述的α二氟代酯类衍生物的合成方法，其反应通式如下所示，其中R选自苯甲脂基、苯醚基、苯甲酰胺基、噻吩甲酰胺基、呋喃甲酰胺基、邻苯二甲酰亚胺基；
n＝2-6；
反应机理如下：
表1用本发明合成二氟乙酸乙酯基烷烃产物的结构如下表所示：
本发明与现有技术相比，具有的优点有：
本申请利用[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯作为二氟乙酸乙酯基自由基前体，在可见光催化下，产生二氟乙酸乙酯基自由基，随后烯烃发生自由基加成，得到α二氟代酯类衍生物。[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯可以通过乙酸碘苯与2,2-二氟丙二酸二乙酯反应方便地制备。此外本专利使用的方法不需要光催化剂、氧化剂，操作简便，反应条件温和。
本申请所用的反应不需要光催化剂和氧化剂，操作简便，反应条件温和；制备出的[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯具有稳定性并且容易制备。
附图说明
图1为实例1的化合的H谱。
图2实例2的化合的H谱。
图3实例3的化合的H谱。
图4实例4的化合的-H谱。
图5实例5的化合的H谱。
图6实例6的化合的H谱。
图7实例7的化合的H谱。
图8实例8的化合的H谱。
图9实例9的化合的H谱。
图10实例10的化合的H谱。
图11实例11的化合的H谱。
图12实例12的化合的H谱。
图13实例13的化合的H谱。
图14实例14的化合的H谱。
具体的实施方式
本发明提供的由[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯作为二氟乙酸乙酯基自由基前体合成α二氟代酯类衍生物方法及其反应通式如下所示：
操作步骤如下：
首先对10mL Schlenk管进行无水无氧处理，通过烘枪高温除去反应管壁、管口以及管内中残留的水分，通过双排管进行氮气和反应管中空气置换，营造一个无水无氧环境，待Schlenk管在氮气氛围中冷却后，将烯烃(0.30mmol)、[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯(0.60mmol)依次加入反应管，用长针头注射器在双排管氮气的保护下取2.00mL无水THF加入反应管中，搅拌下溶解两反应物，在蓝色12W LED灯光照下室温反应。经TLC确认反应完全后，加入大量水洗涤，用乙酸乙酯萃取三次，饱和氯化钠溶液洗涤，取有机相用无水硫酸钠干燥，将溶剂通过旋蒸除去，残留物经硅胶柱层析纯化得到产物(流动相体系为石油醚：乙酸乙酯)。
下面通过实例具体说明：
实施例1
将碘苯二乙酸(4mmol)加入甲苯(4mL)的搅拌溶液中，室温下滴加2-(乙氧羰基)-2,2-二氟乙酸(1.00mL，16mmol)。搅拌30min后，旋干溶剂。在粗混合物中加入甲苯(2mL)，然后再次浓缩混合物以完全去除未反应完全的酸。蒸发后，无需进一步纯化，得到相应的[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯，白色固体，收率92％。1H NMR(400MHz,CDCl3)δ8.32(s,1H),8.17-8.15(d,2H),7.69(t,J＝7.6Hz,1H),7.55(t,J＝6.0Hz,2H),4.27(q,J＝7.2Hz,4H),1.24(t,J＝7.2Hz,6H).13C NMR(100MHz,CDCl3)δ164.41(t,J＝30.0Hz,2C),162.58,161.40,161.20(t,J＝20.0Hz,2C),161.10,160.89,160.79,137.46,135.07,134.99,133.36,131.82,131.79,130.28,129.05,128.25,127.50,125.32,123.09,122.98,104.89(t,J＝262.0Hz,2C),63.99(t,J＝12.0Hz,2C),29.68,29.35,21.41,13.70(t,J＝40.0Hz,2C).19F NMR(376MHz,CDCl3)δ-109.88(s,4F).
实施例2
首先对10mL Schlenk管进行无水无氧处理，通过烘枪高温除去反应管壁、管口以及管内中残留的水分，通过双排管进行氮气和反应管中空气置换，营造一个无水无氧环境，待Schlenk管在氮气氛围中冷却后，将1-苯甲酸酯5-己烯(0.30mmol)、[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯(0.60mmol)依次加入反应管，用长针头注射器在双排管氮气的保护下取2.00mL无水THF打入反应管中，搅拌下溶解两反应物，在蓝色12W LED灯光照下室温反应。经TLC确认反应完全后，加入大量水洗涤，用乙酸乙酯萃取三次，饱和氯化钠溶液洗涤，取有机相用无水硫酸钠干燥，将溶剂通过旋蒸除去，残留物经硅胶柱层析纯化得到产物，无色油状，收率73％。1H NMR(400MHz,CDCl3)δ8.05(d,J＝7.24Hz,2H),7.55(t,J＝7.36Hz,1H),7.43(t,J＝7.72Hz,2H),4.34-4.29(m,4H),2.13-2.00(m,2H),1.80-174(m,2H),1.54-1.42(m,6H),1.34(t,J＝7.12Hz,3H).13C NMR(100MHz,CDCl3)δ166.6,164.3(t,J＝32.7Hz,1C),136.6,132.9,130.4,129.5,128.3,116.3(t,J＝248.5Hz,1C),64.8,64.1,62.7,34.4(t,J＝22.9Hz,1C),28.7,28.5,25.7,21.4(t,J＝4.2Hz,1C),13.9.19F NMR(376MHz,CDCl3)δ-105.91(s,2F).
实施例3
首先对10mL Schlenk管进行无水无氧处理，通过烘枪高温除去反应管壁、管口以及管内中残留的水分，通过双排管进行氮气和反应管中空气置换，营造一个无水无氧环境，待Schlenk管在氮气氛围中冷却后，将(戊-4-烯-1-氧基)苯(0.30mmol)、[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯(0.60mmol)依次加入反应管，用长针头注射器在双排管氮气的保护下取2.00mL无水THF打入反应管中，搅拌下溶解两反应物，在蓝色12W LED灯光照下室温反应。经TLC确认反应完全后，加入大量水洗涤，用乙酸乙酯萃取三次，饱和氯化钠溶液洗涤，取有机相用无水硫酸钠干燥，将溶剂通过旋蒸除去，残留物经硅胶柱层析纯化得到产物，无色油状，收率65％。1H NMR(400MHz,CDCl3)δ7.27(t,J＝7.52Hz,2H),6.95(t,J＝7.36Hz,1H),6.88(d,J＝7.88Hz,2H),4.31(q,J＝7.16,2H),3.95(t,J＝6.32Hz,2H),2.15-2.03(m,2H),1.83-1.76(m,2H),1.54(t,J＝3.76Hz,2H),1.34(t,J＝7.12Hz,3H).13C NMR(100MHz,CDCl3)δ164.7(t,J＝32.77Hz,1C),160.0,133.8,129.5,120.6,116.3(t,J＝248.5Hz,1C),114.5,67.4,67.0,62.8,34.4(t,J＝23.0Hz,1C),29.0,25.7,21.3(t,J＝4.3Hz,1C),14.0.19FNMR(376MHz,CDCl3)δ-105.92(s,2F).HRMS ESI(m/z):calcd forC15H20O3F2[M+Na]+,309.1273,found:309.1272.
实施例4
首先对10mL Schlenk管进行无水无氧处理，通过烘枪高温除去反应管壁、管口以及管内中残留的水分，通过双排管进行氮气和反应管中空气置换，营造一个无水无氧环境，待Schlenk管在氮气氛围中冷却后，将烯丙基4-氰基苯胺(0.30mmol)、[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯(0.60mmol)依次加入反应管，用长针头注射器在双排管氮气的保护下取2.00mL无水THF打入反应管中，搅拌下溶解两反应物，在蓝色12W LED灯光照下室温反应。经TLC确认反应完全后，加入大量水洗涤，用乙酸乙酯萃取三次，饱和氯化钠溶液洗涤，取有机相用无水硫酸钠干燥，将溶剂通过旋蒸除去，残留物经硅胶柱层析纯化得到产物，白色固体，收率85％。1H NMR(400MHz,CDCl3)δ7.88(d,J＝8.36Hz,2H),7.74(d,J＝8.40Hz,2H),6.58(s,1H),4.33(q,J＝7.16,2H),3.53(q,J＝6.76Hz,2H),2.23-2.11(m,2H),1.89-1.82(m,2H),1.35(t,J＝7.12Hz,3H).13C NMR(100MHz,CDCl3)δ166.0,164.1(t,J＝32.51Hz,1C),138.3,132.5,127.7,118.0,116.0(t,J＝248.9Hz,1C),115.1,63.1,54.4,39.4,31.8(t,J＝23.4Hz,1C),29.7,21.8(t,J＝3.9Hz,1C),14.0.19F NMR(376MHz,CDCl3)δ-105.72(s,2F).HRMS ESI(m/z):calcd for C15H16O3F2N2[M+Na]+,333.1021,found:333.1024.
实施例5
首先对10mL Schlenk管进行无水无氧处理，通过烘枪高温除去反应管壁、管口以及管内中残留的水分，通过双排管进行氮气和反应管中空气置换，营造一个无水无氧环境，待Schlenk管在氮气氛围中冷却后，将烯丙基4-溴苯甲酰胺(0.30mmol)、[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯(0.60mmol)依次加入反应管，用长针头注射器在双排管氮气的保护下取2.00mL无水THF打入反应管中，搅拌下溶解两反应物，在蓝色12W LED灯光照下室温反应。经TLC确认反应完全后，加入大量水洗涤，用乙酸乙酯萃取三次，饱和氯化钠溶液洗涤，取有机相用无水硫酸钠干燥，将溶剂通过旋蒸除去，残留物经硅胶柱层析纯化得到产物，淡黄色油状，收率96％。1H NMR(400MHz,CDCl3)δ7.63(d,J＝8.56Hz,2H),7.56(d,J＝8.60Hz,2H),6.45(s,1H),4.32(q,J＝7.12,2H),3.50(q,J＝6.36Hz,2H),2.22-2.10(m,2H),1.87-1.79(m,2H),1.35(t,J＝7.12Hz,3H).13C NMR(100MHz,CDCl3)δ166.8,164.1(t,J＝32.57Hz,1C),133.2,131.8,128.5,126.2,116.0(t,J＝248.8Hz,1C),107.6,63.1,106.4,67.7,67.4,63.0,39.2,31.9(t,J＝23.5Hz,1C),29.6,23.8,21.9(t,J＝3.8Hz,1C),14.0.19F NMR(376MHz,CDCl3)δ-105.77(s,2F).
实施例6
首先对10mL Schlenk管进行无水无氧处理，通过烘枪高温除去反应管壁、管口以及管内中残留的水分，通过双排管进行氮气和反应管中空气置换，营造一个无水无氧环境，待Schlenk管在氮气氛围中冷却后，将(9H-芴-9-基)甲基烯丙基氨基甲酸酯(0.30mmol)、[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯(0.60mmol)依次加入反应管，用长针头注射器在双排管氮气的保护下取2.00mL无水THF打入反应管中，搅拌下溶解两反应物，在蓝色12WLED灯光照下室温反应。经TLC确认反应完全后，加入大量水洗涤，用乙酸乙酯萃取三次，饱和氯化钠溶液洗涤，取有机相用无水硫酸钠干燥，将溶剂通过旋蒸除去，残留物经硅胶柱层析纯化得到产物，白色固体，收率90％。1H NMR(400MHz,CDCl3)δ7.75(d,J＝7.52Hz,2H),7.57(d,J＝7.44Hz,2H),7.39(t,J＝7.36Hz,2H),7.30(t,J＝7.04Hz,2H),4.88(s,1H),4.41(d,J＝6.76Hz,2H),4.1(q,J＝7.16,2H),4.20(t,J＝6.64Hz,1H),3.24(q,J＝6.52Hz,2H),2.15-2.02(m,2H),1.74-1.69(m,2H),1.34(t,J＝7.16Hz,3H).13C NMR(100MHz,CDCl3)δ164.1(t,J＝32.57Hz,1C),156.4,133.9,141.3,127.7,127.1,125.0,120.0,,116.0(t,J＝249.1Hz,1C),107.7,106.4,67.7,67.4,66.6,63.0,47.3,40.2,31.7(t,J＝23.9Hz,1C),29.6,23.9,22.3,14.0.19F NMR(376MHz,CDCl3)δ-105.84(s,2F).HRMS ESI(m/z):calcdfor C22H23O4F2N[M+Na]+,404.1668,found:404.1669.
实施例7
首先对10mL Schlenk管进行无水无氧处理，通过烘枪高温除去反应管壁、管口以及管内中残留的水分，通过双排管进行氮气和反应管中空气置换，营造一个无水无氧环境，待Schlenk管在氮气氛围中冷却后，将烯丙基噻吩-2-甲酰胺(0.30mmol)、[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯(0.60mmol)依次加入反应管，用长针头注射器在双排管氮气的保护下取2.00mL无水THF打入反应管中，搅拌下溶解两反应物，在蓝色12W LED灯光照下室温反应。经TLC确认反应完全后，加入大量水洗涤，用乙酸乙酯萃取三次，饱和氯化钠溶液洗涤，取有机相用无水硫酸钠干燥，将溶剂通过旋蒸除去，残留物经硅胶柱层析纯化得到产物，淡黄色油状，收率70％。1H NMR(400MHz,CDCl3)δ7.53(dd,J＝3.68,0.96Hz,1H),7.47(dd,J＝5.00,0.96Hz,1H),7.068(dd,J＝4.92,3.80,1H),6.44(s,1H),4.32(q,J＝7.12,2H),3.49(q,J＝6.48Hz,2H),2.22-2.09(m,2H),1.86-1.78(m,2H),1.34(t,J＝7.12Hz,3H).13C NMR(100MHz,CDCl3)δ164.1(t,J＝32.57Hz,1C),162.2,138.8,130.0,128.1,127.7,116.0(t,J＝248.8Hz,1C),63.0,39.1,31.9(t,J＝23.4Hz,1C),22.0(t,J＝4.1Hz,1C),14.0.19F NMR(376MHz,CDCl3)δ-105.80(s,2F).HRMS ESI(m/z):calcd forC12H15O3F2NS[M+Na]+,314.0633,found:314.0636.
实施例8
首先对10mL Schlenk管进行无水无氧处理，通过烘枪高温除去反应管壁、管口以及管内中残留的水分，通过双排管进行氮气和反应管中空气置换，营造一个无水无氧环境，待Schlenk管在氮气氛围中冷却后，将(嘧啶-4-基)庚-6-烯胺(0.30mmol)、[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯(0.60mmol)依次加入反应管，用长针头注射器在双排管氮气的保护下取2.00mL无水THF打入反应管中，搅拌下溶解两反应物，在蓝色12W LED灯光照下室温反应。经TLC确认反应完全后，加入大量水洗涤，用乙酸乙酯萃取三次，饱和氯化钠溶液洗涤，取有机相用无水硫酸钠干燥，将溶剂通过旋蒸除去，残留物经硅胶柱层析纯化得到产物，白色固体，收率60％。1H NMR(400MHz,CDCl3)δ8.86(s,1H),8.64(d,J＝4.12Hz,1H),8.18(d,J＝6.00Hz,1H),4.33(q,J＝7.12,2H),2.44(t,J＝7.40Hz,2H),2.12-1.99(m,2H),1.77-1.72(m,2H),1.51-1.46(m,2H),1.35(t,J＝7.16Hz,3H).13C NMR(100MHz,CDCl3)δ172.3,164.4,158.4,158.3,160.0,116.3(t,J＝248.6Hz,1C),110.2,62.8,37.5,34.3(t,J＝23.2Hz,1C),29.7,28.7(d,J＝2.25Hz,1C),24.7,21.3(t,J＝4.02Hz,1C),14.0.19F NMR(376MHz,CDCl3)δ-105.94(s,2F).HRMS ESI(m/z):calcd for C15H21O3F2N3[M+Na]+,330.1624,found:330.1625.
实施例9
首先对10mL Schlenk管进行无水无氧处理，通过烘枪高温除去反应管壁、管口以及管内中残留的水分，通过双排管进行氮气和反应管中空气置换，营造一个无水无氧环境，待Schlenk管在氮气氛围中冷却后，将2-(丙-2-炔-1-基)异吲哚啉-1，3-二酮(0.30mmol)、[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯(0.60mmol)依次加入反应管，用长针头注射器在双排管氮气的保护下取2.00mL无水THF打入反应管中，搅拌下溶解两反应物，在蓝色12WLED灯光照下室温反应。经TLC确认反应完全后，加入大量水洗涤，用乙酸乙酯萃取三次，饱和氯化钠溶液洗涤，取有机相用无水硫酸钠干燥，将溶剂通过旋蒸除去，残留物经硅胶柱层析纯化得到产物，白色固体，收率84％。1H NMR(400MHz,CDCl3)δ7.82(dq,J＝49.28,3.04Hz,4H),6.37-6.29(m,1H),5.93-5.84(m,1H),4.40-4.38(m,2H),4.31(q,J＝7.16,2H),1.33(t,J＝7.16Hz,3H).13C NMR(100MHz,CDCl3)δ167.5,163.4(t,J＝33.89Hz,1C),134.3,132.4(t,J＝8.83Hz,1C),131.9,124.0(t,J＝25.39Hz,1C),123.5,117.72(t,J＝247.2Hz,1C),63.2,50.9,38.1,29.7,13.9.19FNMR(376MHz,CDCl3)δ-104.08(s,2F).HRMSESI(m/z):calcd for C15H13O4F2N[M+Na]+,332.0705,found:332.0706.
实施例10
首先对10mL Schlenk管进行无水无氧处理，通过烘枪高温除去反应管壁、管口以及管内中残留的水分，通过双排管进行氮气和反应管中空气置换，营造一个无水无氧环境，待Schlenk管在氮气氛围中冷却后，将2-烯丙基吲哚啉-1，3-二酮(0.30mmol)、[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯(0.60mmol)依次加入反应管，用长针头注射器在双排管氮气的保护下取2.00mL无水THF打入反应管中，搅拌下溶解两反应物，在蓝色12W LED灯光照下室温反应。经TLC确认反应完全后，加入大量水洗涤，用乙酸乙酯萃取三次，饱和氯化钠溶液洗涤，取有机相用无水硫酸钠干燥，将溶剂通过旋蒸除去，残留物经硅胶柱层析纯化得到产物，无色油状，收率92％。1HNMR(400MHz,CDCl3)δ7.79(dq,J＝47.52,3.08Hz,4H),4.32(q,J＝7.12Hz,2H),3.76(t,J＝7.00Hz,2H),2.20-2.08(m,2H),1.94-1.82(m,2H),1.34(t,J＝7.16Hz,3H).13C NMR(100MHz,CDCl3)δ202.3,168.2,163.9(t,J＝32.52Hz,1C),134.1,131.9,132.3(d,J＝7.30Hz,1C),115.7(t,J＝248.86Hz,1C),107.6,106.3,103.8,67.6,67.4,62.9,53.5,37.1,31.8,29.5(m,1C),23.8(d,J＝2.14Hz,1C),20.9(t,J＝4.24Hz,1C),13.9.19FNMR(376MHz,CDCl3)δ-106.03(s,2F).
实施例11
首先对10mL Schlenk管进行无水无氧处理，通过烘枪高温除去反应管壁、管口以及管内中残留的水分，通过双排管进行氮气和反应管中空气置换，营造一个无水无氧环境，待Schlenk管在氮气氛围中冷却后，将乙烯基磺酰基苯(0.30mmol)、[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯(0.60mmol)依次加入反应管，用长针头注射器在双排管氮气的保护下取2.00mL无水THF打入反应管中，搅拌下溶解两反应物，在蓝色12W LED灯光照下室温反应。经TLC确认反应完全后，加入大量水洗涤，用乙酸乙酯萃取三次，饱和氯化钠溶液洗涤，取有机相用无水硫酸钠干燥，将溶剂通过旋蒸除去，残留物经硅胶柱层析纯化得到产物，无色油状，收率73％。1HNMR(400MHz,CDCl3)δ7.73(d,J＝7.32Hz,2H),7.71(t,J＝7.40Hz,1H),7.61(t,J＝7.88Hz,2H),4.33(q,J＝7.12Hz,2H),3.33-3.28(m,2H),2.59-2.47(m,2H),1.34(t,J＝7.16Hz,3H).13C NMR(100MHz,CDCl3)δ163.0(t,J＝31.90Hz,1C),138.3,134.3,129.6,128.1,114.2(t,J＝250.84Hz,1C),63.6,49.0(t,J＝4.01Hz,1C),29.7,29.5,28.2(t,J＝24.35Hz,1C),13.9.19FNMR(376MHz,CDCl3)δ-105.99(s,2F).
实施例12
首先对10mL Schlenk管进行无水无氧处理，通过烘枪高温除去反应管壁、管口以及管内中残留的水分，通过双排管进行氮气和反应管中空气置换，营造一个无水无氧环境，待Schlenk管在氮气氛围中冷却后，将二甲基(苯基)(乙烯基)硅烷(0.30mmol)、[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯(0.60mmol)依次加入反应管，用长针头注射器在双排管氮气的保护下取2.00mL无水THF打入反应管中，搅拌下溶解两反应物，在蓝色12W LED灯光照下室温反应。经TLC确认反应完全后，加入大量水洗涤，用乙酸乙酯萃取三次，饱和氯化钠溶液洗涤，取有机相用无水硫酸钠干燥，将溶剂通过旋蒸除去，残留物经硅胶柱层析纯化得到产物，无色油状，收率75％。1HNMR(400MHz,CDCl3)δ7.31(dd,J＝5.60,3.88,2.20Hz,2H),7.15(d,J＝2.08Hz,2H),7.19(d,J＝1.52Hz,1H),4.12(q,J＝7.12Hz,2H),1.90-1.77(m,2H),1.15(t,J＝7.12Hz,3H),0.71-0.67(m,2H),0.13(s,6H).13CNMR(100MHz,CDCl3)δ164.4(t,J＝32.96Hz,1C),137.9,137.6,133.9(d,J＝4.40Hz,1C),133.5,129.6,129.3,128.8,128.0,127.9,127.7,116.8(t,J＝248.76Hz,1C),63.0,62.7,29.4(t,J＝24.16Hz,1C),14.0,6.9(t,J＝2.79Hz,1C),-3.4(t,J＝-25.67Hz,1C).19F NMR(376MHz,CDCl3)δ-107.39(s,2F).HRMS ESI(m/z):calcd for C14H20O2F2Si[M+Na]+,309.1093,found:309.1097.
实施例13
首先对10mL Schlenk管进行无水无氧处理，通过烘枪高温除去反应管壁、管口以及管内中残留的水分，通过双排管进行氮气和反应管中空气置换，营造一个无水无氧环境，待Schlenk管在氮气氛围中冷却后，将烯丙基苯甲酰胺(0.30mmol)、[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯(0.60mmol)依次加入反应管，用长针头注射器在双排管氮气的保护下取2.00mL无水THF打入反应管中，搅拌下溶解两反应物，在蓝色12W LED灯光照下室温反应。经TLC确认反应完全后，加入大量水洗涤，用乙酸乙酯萃取三次，饱和氯化钠溶液洗涤，取有机相用无水硫酸钠干燥，将溶剂通过旋蒸除去，残留物经硅胶柱层析纯化得到产物，无色油状，收率60％。1HNMR(400MHz,CDCl3)δ7.75(d,J＝7.44Hz,2H),7.51(t,J＝7.32Hz,1H),7.42(d,J＝7.60Hz,2H),6.61(s,1H),4.32(q,J＝7.16,2H),3.52(q,J＝6.56Hz,2H),2.22-2.10(m,2H),1.87-1.80(m,2H),1.34(t,J＝7.12Hz,3H).13C NMR(100MHz,CDCl3)δ168.5,164.1(t,J＝32.63Hz,1C),134.0,131.8,128.7,127.0,116.0(t,J＝248.8Hz,1C),63.6,63.0,39.3,31.9,31.8(t,J＝23.4Hz,1C),29.7(t,J＝3.96Hz,1C),29.4,22.7,21.9(t,J＝4.0Hz,1C),14.1,13.9,13.8.19FNMR(376MHz,CDCl3)δ-105.72(s,2F).HRMS ESI(m/z):calcd for C14H17O3F2N[M+H]+,286.1249,found:286.1249。
实施例14
首先对10mL Schlenk管进行无水无氧处理，通过烘枪高温除去反应管壁、管口以及管内中残留的水分，通过双排管进行氮气和反应管中空气置换，营造一个无水无氧环境，待Schlenk管在氮气氛围中冷却后，将烯丙基硫代-2-甲酰胺(0.30mmol)、[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯(0.60mmol)依次加入反应管，用长针头注射器在双排管氮气的保护下取2.00mL无水THF打入反应管中，搅拌下溶解两反应物，在蓝色12W LED灯光照下室温反应。经TLC确认反应完全后，加入大量水洗涤，用乙酸乙酯萃取三次，饱和氯化钠溶液洗涤，取有机相用无水硫酸钠干燥，将溶剂通过旋蒸除去，残留物经硅胶柱层析纯化得到产物，黄色油，收率50％。1HNMR(400MHz,CDCl3)δ7.44(d,J＝0.92Hz,1H),7.11(dd,J＝3.44,0.48Hz,2H),6.50(q,J＝1.72Hz,1H),6.43(s,1H),4.33(q,J＝7.16Hz,2H),3.50(q,J＝6.76cHz,2H),2.23-2.10(m,2H),1.86-1.79(m,2H),1.35(t,J＝7.12Hz,3H).13C NMR(100MHz,CDCl3)δ164.1,158.5,147.8,143.9,114.3,112.2,63.0,38.2,31.7(d,J＝23.39Hz,1C),22.1(d,J＝3.91Hz,1C),14.0.19FNMR(376MHz,CDCl3)δ-105.94(s,2F).HRMSESI(m/z):calcd for C15H21O3F2N3[M+H]+,276.1042,found:276.1044。

Claims (2)

1.一种由末端烯烃合成α二氟代酯类衍生物的方法，其特征在于：由[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯作为二氟乙酸乙酯自由基前体，在光催化由末端烯烃得到α二氟代酯类衍生物的方法；
具体步骤：在无水无氧条件下加入末端烯烃、[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯和四氢呋喃，在蓝色12W LED灯光照下室温反应，反应结束后，经萃取，洗涤，干燥，柱层析分离得到α二氟代酯类衍生物；
反应通式如下：
其中R选自苯甲脂基、苯醚基、苯甲酰胺基、噻吩甲酰胺基、呋喃甲酰胺基、邻苯二甲酰亚胺基；n＝2-6。
2.根据权利要求1所述的由末端烯烃合成α二氟代酯类衍生物的方法，其特征在于：以[双(2-(乙氧羰基)-2,2-二氟乙酰氧基)碘]苯为二氟代试剂。
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Citations (3)

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Publication number Priority date Publication date Assignee Title
JP2012250964A (ja) * 2011-06-07 2012-12-20 Sagami Chemical Research Institute （トリフルオロメチルスルホニル）ベンゼン誘導体の製造方法
CN112321553A (zh) * 2020-10-30 2021-02-05 天津科技大学 由芳基炔酸酯合成3位二氟甲基取代香豆素衍生物的方法
WO2021169199A1 (zh) * 2020-02-24 2021-09-02 江西师范大学 α-羰基烯基酯类化合物及其制备方法和应用

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012250964A (ja) * 2011-06-07 2012-12-20 Sagami Chemical Research Institute （トリフルオロメチルスルホニル）ベンゼン誘導体の製造方法
WO2021169199A1 (zh) * 2020-02-24 2021-09-02 江西师范大学 α-羰基烯基酯类化合物及其制备方法和应用
CN112321553A (zh) * 2020-10-30 2021-02-05 天津科技大学 由芳基炔酸酯合成3位二氟甲基取代香豆素衍生物的方法

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