CN115010600B - 一种基于芳基碳氟键羧基化反应合成多氟芳基羧酸类化合物的方法 - Google Patents

一种基于芳基碳氟键羧基化反应合成多氟芳基羧酸类化合物的方法 Download PDF

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CN115010600B
CN115010600B CN202210620427.6A CN202210620427A CN115010600B CN 115010600 B CN115010600 B CN 115010600B CN 202210620427 A CN202210620427 A CN 202210620427A CN 115010600 B CN115010600 B CN 115010600B
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余达刚
伯知豫
颜思顺
高田宇
宋磊
冉川昆
何轶
章炜
曹光梅
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Sichuan University
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Abstract

本发明公开了一种基于芳基碳氟键羧基化反应合成多氟芳基羧酸类化合物的方法，属于有机合成技术领域，具体包括以下步骤：将反应底物、光催化剂、氢原子转移试剂、还原剂和碱加入反应容器中，然后在CO2气氛下加入溶剂，在光照射条件下，室温搅拌反应。对反应产物进行分离纯化，制得多氟芳基羧酸类化合物。本发明方案具有反应条件温和、反应底物范围广、产率与区域选择性良好、原料廉价易得等特点，可高效实现芳基碳氟键的断裂及其羧基化反应，合成重要的多氟芳基羧酸类化合物，具有良好的应用前景。

Description

一种基于芳基碳氟键羧基化反应合成多氟芳基羧酸类化合物 的方法
技术领域
本发明属于有机合成技术领域，具体涉及一种基于芳基碳氟键羧基化反应合成多氟芳基羧酸类化合物的方法。
背景技术
氟元素是自然界中电负性最大的元素，将氟原子引入功能分子中，可改变该分子的物理、化学性质以及生理活性。多氟芳基羧酸作为一种重要的多氟砌块，具有特殊的性质，在医药、农药、有机光电材料等领域中具有广泛的应用。以廉价易得的多氟化合物为底物，通过其C-F键的选择性官能团反应可构建具有重要应用价值的部分氟代化合物。该策略步骤经济性高，是构建部分氟代化合物最有效的手段之一。然而，由于C-F键的键解离能高，氟原子的亲金属性强，C-F键的选择性断裂及其官能团化反应存在较大的挑战。
另一方面，二氧化碳(CO2)具有廉价易得、无毒无害、可循环再生等优点，在合成化学中是一种优良的碳一(C1)合成子，可用于多种大宗化学品及精细化学品的合成。以二氧化碳为羧基源，易于得到的多氟芳烃为底物，通过多氟芳烃C-F键的选择性羧基化反应可构建重要的多氟芳基羧酸类化合物。但目前为止该领域的报道较少，且主要通过电还原或过渡金属催化等手段来实现，存在需使用牺牲阳极、当量金属还原剂，额外引入导向基以及反应条件苛刻等缺点，具有较大的发展空间。温和条件下廉价还原剂参与的芳基C-F键的选择性羧基化反应亟待发展。
发明内容
针对现有技术的不足，本发明的目的是提供一种基于芳基碳氟键羧基化反应合成多氟芳基羧酸类化合物的方法，可有效解决现有技术中针对芳基C-F键选择性羧基化反应需使用牺牲阳极或当量金属还原剂、额外引入导向基以及反应条件苛刻等问题，能够在室温下以绿色廉价的甲酸盐为还原剂，合成多氟芳基羧酸类化合物，具有反应条件温和、反应底物范围广、产率及区域选择性良好、原料廉价易得的特点。
为了达到上述目的，本发明所采用的技术方案是：提供一种基于芳基碳氟键羧基化反应合成多氟芳基羧酸类化合物的方法，包括以下步骤：
将反应底物、光催化剂、氢原子转移试剂、还原剂和碱加入反应容器中，然后在CO2气氛下加入溶剂，在光照条件下，室温搅拌反应0.1～72h，再分离、纯化，得多氟芳基羧酸类化合物；
反应底物的结构通式如式(I)或式(II)所示：
其中，R1、R2、R4和R5分别独立的为氢原子或氟原子；R3为取代苯基、萘基、芴基、杂芳基、酯基、羧基、酰胺基、烷基、烯基、炔基、氰基、硼基、硅基、膦基、胺基、硫醚基、烷氧基、酰氧基或芳氧基；R7和R8分别独立的为氢原子或氟原子；R6和R9为苯基、萘基、芴基、杂芳基、酯基、羧基、酰胺基、烷基、烯基、炔基、氰基、硼基、硅基、膦基、胺基、硫醚基、烷氧基、酰氧基或芳氧基。
在上述技术方案的基础上，本发明还可以做如下改进。
进一步，还原剂、反应底物、光催化剂、氢原子转移试剂和碱的摩尔比为1～5:1:0.001～0.2:0.01～2:1～10。
进一步，反应底物为五氟芳烃类化合物、四氟芳烃类化合物或三氟芳烃类化合物；其中，
五氟芳烃类化合物为如下化合物中的一种：
四氟芳烃类化合物为如下化合物中的一种：
三氟芳烃类化合物为如下化合物中的一种：
进一步，光催化剂为D-A型光催化剂或有机金属光催化剂。
进一步，还原剂为甲酸盐、草酸盐、有机胺、汉斯酯或含氮杂环。
进一步，氢原子转移试剂为N,N-二甲基乙醇胺、芳基硫酚、杂芳基硫醇、烷基硫醇、含氮杂环、苯甲酸盐、烷氧基碱或硅氧基碱。
进一步，芳基硫酚为2,4,6-三异丙基苯硫酚、2,4,6-三叔丁基苯硫酚、4-叔丁基苯硫酚或2-甲氧羰基苯硫酚；所述烷基硫醇为环己基硫醇、巯基乙酸乙酯或2-巯基丙酸乙酯。
进一步，溶剂为MeCN、DMF、DMAc、DMSO、NMP。
进一步，碱为碳酸盐、碳酸氢盐、氟化盐、烷氧基碱、磷酸盐、磷酸氢盐、羧酸盐或有机碱。
进一步，反应容器中二氧化碳压力为0.1～30倍大气压；光源与反应容器间的距离为0.1～10cm，光的波长为300～560nm，光源功率为1～100W。
本发明的有益效果是：
1、本发明提供了一种基于芳基碳氟键羧基化反应合成多氟芳基羧酸类化合物的方法。在可见光催化下，以五氟芳烃类化合物、四氟芳烃类化合物或三氟芳烃类化合物作为反应底物，二氧化碳作为羧酸源，同时加入光催化剂、氢原子转移试剂、还原剂和碱，制得多氟芳基羧酸类化合物；本方法具有反应条件温和、反应底物反应广、产率及区域选择性良好、原料廉价易得的特点；
2、本发明提供的合成方法对于五氟芳烃类化合物、四氟芳烃类化合物以及三氟芳烃类化合物均具有良好的反应性，具有反应底物范围广、产率及区域选择性良好的特点；
3、本发明首次实现了可见光促进多氟芳烃碳氟键的选择性羧基化反应。此反应在温和条件下高效地实现了芳基C-F键的选择性断裂并引入重要的羧基官能团，制得重要的多氟芳基羧酸类化合物，具有广泛的应用前景。
附图说明
图1为本发明的合成机理示意图。
具体实施方式
下面结合实施例对本发明的具体实施方式做详细的说明。
实施例1
一种基于芳基碳氟键羧基化反应合成多氟芳基羧酸类化合物的方法，合成反应式如式(1-1)所示。
合成方法包括以下步骤：
将配有搅拌子的25ml Schlenk反应管在真空下加热干燥后，加入反应底物五氟芳烃类化合物(0.2mmol，1.0equiv，若底物为固体)和光催化剂Ir(ppy)2(dtbbpy)PF6(4.6mg，0.025mmol，2.5mol％)。随后将反应管移至手套箱内，依次加入还原剂HCO2K(33.6mg，0.4mmol，2equiv)，氢原子转移试剂N,N-二甲基乙醇胺(DABCO，13.4mg，0.12mmol，60mol％)，碱CsF(76mg，0.5mmol，2.5equiv)，碱Cs2CO3(78.2mg，0.24mmol，1.2equiv)。之后使用反应管对应旋塞密封反应管，移出手套箱，用双排管将反应管抽置换为CO2氛围，重复3次。随后在CO2氛围下使用注射器依次将反应底物五氟芳烃类化合物(若底物为液体)和超干DMF(2mL)注射进反应管中。加料完毕后立刻密封该反应管。将反应管固定在水浴锅中，将反应所用搅拌器转速调至650r/min，使用30W蓝色LED灯(波长为450nm左右)在0.5cm远处照射，并使用风扇散热，使反应温度维持在25-30℃。搅拌反应30～34小时后，向反应混合物加入5mL乙酸乙酯稀释，再加入2mL 2N盐酸以及5mL水淬灭反应，搅拌1分钟。随后，使用3mL乙酸乙酯萃取反应液3次，合并有机相并使用旋蒸彻底除去残留溶剂。得到的粗产物用2mL甲醇与2mL***转移至25mL茄形瓶中，在0℃下滴加三甲硅基重氮甲烷(0.3mL，3equiv，0.6mmol，2M的正己烷溶液)，在室温下反应1小时。之后，继续在0℃下滴加三甲硅基重氮甲烷(0.3mL，3equiv，0.6mmol，2M正己烷溶液)，在室温下反应1小时。酯化结束后，使用柱色谱分离纯化。纯化条件为：使用石油醚:二氯甲烷＝7:1～3:1(v:v)的混合溶剂冲洗，得到目标产物。具体反应结果见表1。
表1.以五氟芳烃类化合物为底物及其所对应产物的收率
注：表1中标准反应条件与上述描述相同，区域选择性由粗GC确定，产率为分离收率；a为反应42h；b为使用2.5当量HCO2K；c为使用2.5当量CsF和1.5当量Cs2CO3作为碱，反应30h；d为反应48h；e为使用2.5当量Cs2CO3作为碱，2mL DMF和300μL DMSO作为混合溶剂。
以上实验结果表明，氟芳烃类化合物均以较高的产率、良好的区域选择性选择性得到四氟芳基羧酸类化合物。多种官能团如叔丁基、甲硫基、甲氧基、环丙基、三氟甲氧基、氟原子以及苄基C-H键等都可兼容于该反应体系。芴基、萘基以及二苯并呋喃、噻吩、呋喃等杂环也能兼容于该反应体系。非联苯类型的五氟芳烃也能顺利发生目标反应。
实施例2
一种基于芳基碳氟键羧基化反应合成多氟芳基羧酸类化合物的方法，合成反应式如式(1-2)所示。
合成方法包括以下步骤：
将配有搅拌子的25ml Schlenk反应管在真空下加热干燥后，加入反应底物四氟芳烃类化合物(0.2mmol，1.0equiv，若为底物为固体)和光催化剂Ir(ppy)2(dtbbpy)PF6(4.6mg，0.025mmol，2.5mol％)。随后将反应管移至手套箱内，依次加入还原剂HCO2K(33.6mg，0.4mmol，2equiv)，氢原子转移试剂DABCO(13.4mg，0.12mmol，60mol％)，碱CsF(76mg，0.5mmol，2.5equiv)，碱Cs2CO3(78.2mg，0.24mmol，1.2equiv)。之后使用反应管对应旋塞密封反应管，移出手套箱，用双排管将反应管抽置换为CO2氛围，重复3次。随后在CO2氛围下使用注射器依次将反应底物三氟芳烃类化合物(若底物为液体)、超干DMF(2mL)注射进反应管中。加料完毕后立刻密封该反应管。将反应管固定在水浴锅中，将反应所用搅拌器转速调至650r/min，使用30W蓝色LED灯(波长为450nm左右)在0.5cm远处照射，并使用风扇散热，使反应温度维持在25-30℃。搅拌反应12～72h小时后，向反应混合物加入5mL乙酸乙酯稀释，再加入2mL 2N盐酸以及5mL水淬灭反应，搅拌1分钟。随后，使用3mL乙酸乙酯萃取反应液3次，合并有机相并使用旋蒸彻底除去残留溶剂。得到的粗产物用2mL甲醇与2mL***转移至25mL茄形瓶中，在0℃下滴加三甲硅基重氮甲烷(0.2mL，2equiv，0.4mmol，2M的正己烷溶液)，在室温下反应1小时。之后，继续在0℃下滴加三甲硅基重氮甲烷(0.2mL，2equiv，0.4mmol，2M正己烷溶液)，在室温下反应1小时。酯化结束后，使用柱色谱分离纯化。纯化条件为：使用石油醚:二氯甲烷＝7:1～2:1(v:v)的混合溶剂冲洗，得到目标产物。具体反应结果见表2。
表2.以四氟芳烃类化合物为底物及其所对应产物的收率
注：表2中标准反应条件与上述描述相同，区域选择性由粗GC确定；a为使用3当量甲酸钾。
上述实验数据表明，电中性以及供电子基取代的四氟芳烃也能顺利发生碳氟键的羧基化反应，并以中等的收率以及区域选择性得到其余方法难以合成的三氟芳基羧酸类产物。
实施例3
一种基于芳基碳氟键羧基化反应合成多氟芳基羧酸类化合物的方法，合成反应式如式(1-3)所示。
合成方法包括以下步骤：
将配有搅拌子的25ml Schlenk反应管在真空下加热干燥后，加入反应底物三氟芳烃类化合物(0.2mmol，1.0equiv，若为底物为固体)和光催化剂Ir(ppy)2(dtbbpy)PF6(4.6mg，0.025mmol，2.5mol％)。随后将反应管移至手套箱内，依次加入还原剂HCO2K(42.0mg，0.5mmol，2.5equiv)，氢原子转移试剂DABCO(13.4mg，0.12mmol，60mol％)，碱Cs2CO3(162.9mg，0.5mmol，2.5equiv)。之后使用反应管对应旋塞密封反应管，移出手套箱，用双排管将反应管抽置换为CO2氛围，重复3次。随后在CO2氛围下使用注射器依次将反应底物三氟芳烃类化合物(若底物为液体)、超干DMF(2mL)、超干DMSO(300μL)注射进反应管中。加料完毕后立刻密封该反应管。将反应管固定在水浴锅中，将反应所用搅拌器转速调至650r/min，使用30W蓝色LED灯(波长为450nm左右)在0.5cm远处照射，并使用风扇散热，使反应温度维持在25-30℃。搅拌反应24-38小时后，向反应混合物加入5mL乙酸乙酯稀释，再加入2mL 2N盐酸以及5mL水淬灭反应，搅拌1分钟。随后，使用3mL乙酸乙酯萃取反应液3次，合并有机相并使用旋蒸彻底除去残留溶剂。得到的粗产物用2mL甲醇与2mL***转移至25mL茄形瓶中，在0℃下滴加三甲硅基重氮甲烷(0.2mL，2equiv，0.4mmol，2M的正己烷溶液)，在室温下反应1小时。之后，继续在0℃下滴加三甲硅基重氮甲烷(0.2mL，2equiv，0.4mmol，2M正己烷溶液)，在室温下反应1小时。酯化结束后，使用柱色谱分离纯化。纯化条件为：使用石油醚:二氯甲烷＝5:1～2:1(v:v)或石油醚:乙酸乙酯＝50:1～5:1(v:v)的混合溶剂冲洗，得到目标产物。具体反应结果见表3。
表3.以三氟芳烃类化合物为底物及其所对应产物的收率
注：表3中标准反应条件与上述相同，产物为单一构型，产率为分离收率；a为反应32h；b为使用3当量HCO2K；c使用DMSO作为溶剂，反应24h；d为使用2mol％Ir(ppy)2(dtbbpy)PF6，50mol％DABCO，2当量HCO2K，反应32h；e为使用3.5当量HCO2K。
以上实验结果表明，三氟芳烃类底物也可顺利发生碳氟键羧基化反应，并以单一构型得到目标产物。酯基、氰基、磺酰胺基、氟原子、吡啶等多种吸电子基，以及甲氧基、噻吩、长链烷基等多种供电子基均可兼容于该反应体系。一些天然产物衍生物以及商业可得的液晶材料分子也可顺利发生碳氟键羧基化反应，生成其余方法难以合成的二氟芳基羧酸产物。
实验例1
本实验例1以4'-(叔丁基)-2,3,4,5,6-五氟-1,1'-联苯作为反应底物，通过改变反应条件，考察对反应产率的影响，反应条件：1a底物(0.2mmol，1equiv)，Ir(ppy)2(dtbbpy)PF6(0.05mmol，2.5mol％，4.6mg)，HCO2K(2equiv，33.6mg)，DABCO(0.12mmol，60mol％，13.4mg)，CsF(0.5mmol，2.0equiv，76mg)，Cs2CO3(0.24mmol，1.2equiv,78.2mg)，超干溶剂DMF(2ml)，实验结果见表4。
反应方程式如下所示：
表4.以4'-(叔丁基)-2,3,4,5,6-五氟-1,1'-联苯作为反应底物在不同反应条件下的产物收率
注：表4中为分离收率。括号内为以二溴甲烷为核磁氢谱内标的核磁收率；a为使用50mol％DABCO，2.5当量Cs2CO3作为单一碱，反应24h；b为使用2mol％Ir(ppy)2(dtbbpy)PF6，10mol％2,4,6-三异丙基苯硫酚，2.5当量Cs2CO3作为单一碱，反应32h。
由上表4数据结果看出，在本发明反应条件下产率高达78％。一系列控制实验表明，光照、光催化剂、CO2、还原剂对反应起到不可或缺的作用，缺少任意一项无法得到或只能得到痕量的目标产物。氢原子转移试剂以及碱对该反应起到显著的促进作用。当使用其他光敏剂或氢原子转移试剂时，产率大幅下降，主要为原料剩余增多或脱氟氢化副产物增多。更换CsF/Cs2CO3为单一组分碱时产率明显下降，原料剩余增多或脱氟氢化副产物增多。更换溶剂为MeCN时反应无法发生；更换溶剂为DMSO时产率下降，脱氟氢化的副产物明显增多。
另外，在现有实验研究结果的基础上，发明人提出反应机理，如图1所示。首先，DABCO与激发态光敏剂发生单电子转移(SET)过程得到还原态光敏剂与DABCO自由基阳离子。随后DABCO自由基阳离子与HCO2K发生氢原子转移(HAT)过程，得到质子化的DABCO和二氧化碳自由基阴离子。然后，二氧化碳自由基阴离子通过单电子转移(SET)过程还原多氟芳烃底物为多氟芳基自由基。该芳基自由基与还原态光敏剂通过单电子转移(SET)过程被还原为多氟芳基碳负离子，最后亲核进攻二氧化碳反应生成多氟芳基羧酸盐，经过酸化以及酯化处理后得到目标产物。
对本发明所制得的产物进行了核磁共振和质谱表征分析。核磁和质谱表征数据结果与所得产物一致。具体表征数据如下：
4'-(叔丁基)-2,3,5,6-四氟-[1,1'-联苯]-4-甲酸甲酯
16.4Hz),123.33,110.78(t,J＝15.8Hz),53.21,15.38,9.85；19F NMR(376MHz,Chloroform-d)δ-139.06--141.87(m),-141.39--144.60(m)；HRMS(ESI+):calculated for C18H16F4NaO2 +[M+Na]+363.0979,found 363.0979.
2,3,5,6-四氟-4'-(甲硫基)-[1,1'-联苯]-4-甲酸甲酯
(t,J＝15.9Hz),53.25,15.09；19F NMR(376MHz,Chloroform-d)δ-139.24--139.92(m),-142.53--142.94(m)；HRMS(ESI+):calculated for C15H11F4O2S+[M+H]+331.0410,found331.0413.
2,3,5,6-四氟-4'-甲氧基-[1,1'-联苯]-4-甲酸甲酯
MHz,Chloroform-d)δ-139.79--139.95(m),-143.01--143.18(m)；HRMS(ESI+):calculatedfor C15H11F4NO3 +[M+H]+315.0639,found 315.0635.
4'-环丙基-2,3,5,6-四氟-[1,1'-联苯]-4-甲酸甲酯
Hz),125.69,123.80(t,J＝16.5Hz),123.59,110.88(t,J＝15.8Hz),53.18,34.79,31.12；19F NMR(376MHz,Chloroform-d)δ-139.60--140.10(m),-142.51--143.09(m)；HRMS(ESI+):calculated for C17H13F4O2 +[M+H]+325.0846,found 325.0841.
2,3,5,6-四氟-4'-(三氟甲氧基)-[1,1'-联苯]-4-甲酸甲酯
131.73(t,J＝2.3Hz),125.07(t,J＝2.5Hz),122.30(t,J＝16.3Hz),121.02,120.39(q,J＝258.2Hz),111.83(t,J＝16.0Hz),53.27；19F NMR(376MHz,Chloroform-d)δ-57.88,-138.11--141.04(m),-141.73--145.64(m)；HRMS(ESI+):calculated for C15H8F7O3 +[M+H]+369.0356,found 369.0362.
2,3,4',5,6-五氟-[1,1'-联苯]-4-甲酸甲酯
122.72(t,J＝16.5Hz),122.40(d,J＝2.8Hz),116.00(d,J＝21.9Hz),111.36(t,J＝15.8Hz),53.32；19F NMR(376MHz,Chloroform-d)δ-110.46,-138.79--139.71(m),-142.23--142.87(m)；HRMS(ESI+):calculated for C14H8F5O2 +[M+H]+303.0439,found303.0436.
2,3,5,6-四氟-3',4'-二甲基-[1,1'-联苯]-4-甲酸甲酯
NMR(376MHz,Chloroform-d)δ-139.71--140.08(m),-142.34--142.81(m)；HRMS(ESI+):calculated for C12H13F4O2 +[M+H]+313.0846,found 313.0842.
2,3,5,6-四氟-3',4'-二甲氧基-[1,1'-联苯]-4-甲酸甲酯
性状：白色固体
1H NMR(400MHz,Chloroform-d)δ7.08(dq,J＝8.3,1.6Hz,1H),7.03-6.96(m,2H),4.00(s,-142.19--143.63(m)；HRMS(ESI+):calculated for C16H13F4O4 +[M+H]+345.0744,found345.0738.
4-(1,2-二甲亚氧基苯-5)-2,3,5,6-四氟苯甲酸甲酯
110.83(t,J＝15.8Hz),110.21(t,J＝2.3Hz),108.64,101.60,53.25；19F NMR(376MHz,Chloroform-d)δ-138.67--140.56(m),-141.93--143.30(m)；HRMS(ESI+):calculated forC15H9F4O4 +[M+H]+329.0431,found 329.0428.
2,3,5,6-四氟-4'-甲氧基-3'-(三氟甲基)-[1,1'-联苯]-4-甲酸甲酯
(m),123.09(q,J＝108.4Hz),122.13(t,J＝60.2Hz),119.28(q,J＝31.3Hz),118.21,112.26,111.40(t,J＝16.1Hz),56.10,53.29；19F NMR(376MHz,Chloroform-d)δ-62.89,-137.57--140.78(m),-140.78--144.34(m)；HRMS(ESI+):calculated for C16H10F7O3 +[M+H]+383.0513,found 383.0511.
2,3,5,6-四氟-3',5'-二甲基-[1,1'-联苯]-4-甲酸甲酯
NMR(376MHz,Chloroform-d)δ-139.35--140.56(m),-141.81--143.10(m)；HRMS(ESI+):calculated for C16H13F4O2 +[M+H]+313.0846,found 313.0848.
2,3,5,6-四氟-4'-甲氧基-3',5'-二甲基-[1,1'-联苯]-4-甲酸甲酯
calculated for C17H15F4O3 +[M+H]+343.0952,found 343.0957.
2,3,5,6-四氟-2'-苯氧基-[1,1'-联苯]-4-甲酸甲酯
120.55(t,J＝18.5Hz),119.54,117.91,117.83-117.30(m),111.68(t,J＝15.9Hz),53.26；19F NMR(376MHz,Chloroform-d)δ-139.20--139.34(m),-140.07--140.21(m)；HRMS(ESI+):calculated for C20H13F4O3 +[M+H]+377.0795,found 377.0797.
2,3,5,6-四氟-2',4'-二甲基-[1,1'-联苯]-4-甲酸甲酯
19.5Hz),123.08(t,J＝1.9Hz),111.51(t,J＝15.8Hz),53.31,21.26,19.58；19F NMR(376MHz,Chloroform-d)δ-139.65--139.79(m),-139.79--139.94(m)；HRMS(ESI+):calculated for C16H13F4O2 +[M+H]+313.0846,found 313.0843.
4-(9,9-二甲基芴-2)-2,3,5,6-四氟--苯甲酸甲酯
(t,J＝2.1Hz),128.11,127.19,125.02,124.46(t,J＝2.4Hz),124.33(t,J＝16.0Hz),122.73,120.51,120.18,110.88(t,J＝15.7Hz),53.28,47.07,26.97；19F NMR(376MHz,Chloroform-d)δ-139.46--139.96(m),-142.24--142.65(m)；HRMS(ESI+):calculated forC23H17F4O2 +[M+H]+401.1159,found401.1157.
2,3,5,6-四氟-4-(萘-2)-苯甲酸甲酯
127.43,126.79,126.71(t,J＝1.9Hz),123.94,123.88(t,J＝16.5Hz),111.37(t,J＝15.9Hz),53.32；19F NMR(376MHz,Chloroform-d)δ-138.22--140.07(m),-141.84--142.90(m)；HRMS(ESI+):calculated for C18H11F4O2 +[M+H]+335.0690,found 335.0686.
2,3,5,6-四氟-4-(6-甲氧基萘-2)-苯甲酸甲酯
134.83,129.95,129.90(t,J＝2.3Hz),128.38,127.22(t,J＝2.1Hz),127.14,123.98(t,J＝16.5Hz),121.48,119.68,110.90(t,J＝15.8Hz),105.55,55.37,53.27；19F NMR(376MHz,Chloroform-d)δ-139.51--139.75(m),-142.46--142.73(m)；HRMS(ESI+):calculated forC19H13F4O3 +[M+H]+365.0795,found 365.0790.
4-(二苯并呋喃-2)-2,3,5,6-四氟苯甲酸甲酯
J＝248.9,14.2,4.4Hz),128.11,125.58,124.93,124.62(t,J＝2.3Hz),123.66(t,J＝16.4Hz),123.46,123.14,121.04,120.81,113.50(t,J＝2.3Hz),111.87,111.43(t,J＝15.9Hz),53.34；19F NMR(376MHz,Chloroform-d)δ-139.04--139.52(m),-142.01--142.57(m)；HRMS(ESI+):calculated for C20H11F4O3 +[M+H]+375.0639,found 375.0637.
2,3,5,6-四氟-4-(噻吩-2)-苯甲酸甲酯
127.51,127.16-126.79(m),117.52(t,J＝14.5Hz),109.82(t,J＝15.5Hz),53.24；19F NMR(376MHz,Chloroform-d)δ-139.05--139.34(m),-139.41--139.68(m)；HRMS(ESI+):calculated for C12H7F4O2S+[M+H]+291.0097,found 291.0095.
2,3,5,6-四氟-4-(呋喃-2)-苯甲酸甲酯
性状：白色固体
109.88(t,J＝15.6Hz),53.21；19F NMR(376MHz,Chloroform-d)δ-139.43--140.00(m),-140.44--140.98(m)；HRMS(ESI+):calculated for C12H7F4O3 +[M+H]+275.0326,found275.0323.
2,3,5,6-四氟-4-(5-甲基呋喃-2)-苯甲酸甲酯
7.3Hz),114.04(t,J＝13.5Hz),108.87(t,J＝15.5Hz),108.44,53.12,13.78；19F NMR(376MHz,Chloroform-d)δ-139.88--140.10(m),-141.15--141.43(m)；HRMS(ESI+):calculated for C13H9F4O3 +[M+H]+289.0482,found 289.0478.
4-(二苯氨基)-2,3,5,6-四氟苯甲酸甲酯
122.12,53.18；19F NMR(376MHz,Chloroform-d)δ-134.99--141.41(m),-141.41--146.57(m)；HRMS(ESI+):calculated for C20H14F4NO2 +[M+H]+376.0955,found 376.0954.
2,3,5,6-四氟-4'-(戊氧基)-[1,1'-联苯]-4-甲酸甲酯
160.17,146.21-143.40(m),145.44-142.18(m),131.38(t,J＝2.5Hz),123.71(t,J＝16.1Hz),118.29,114.66,110.43(t,J＝15.7Hz),68.07,53.20,28.84,28.15,22.42,13.99；19F NMR(376MHz,Chloroform-d)δ-138.20--142.39(m),-141.76--146.57(m)；HRMS(ESI+):calculated for C19H19F4O3 +[M+H]+371.1265,found 371.1262.
2,3,5,6-四氟-4'-(庚氧基)-[1,1'-联苯]-4-甲酸甲酯
160.18,146.48-143.61(m),145.20-142.41(m),131.38(t,J＝2.4Hz),123.71(t,J＝16.4Hz),118.28,114.66,110.43(t,J＝15.7Hz),68.09,53.19,31.76,29.14,29.03,25.96,22.59,14.06；19FNMR(376MHz,Chloroform-d)δ-139.06--140.24(m),-142.96--143.81(m)；HRMS(ESI+):calculated for C21H23F4O3 +[M+H]+399.1578,found 399.1574.
3,5-二氟-[1,1'-联苯]-4,4'-二甲酸甲酯
141.86(t,J＝2.2Hz),130.61,130.33,126.96,110.99-110.43(m),109.83(t,J＝18.1Hz),52.78,52.27；19F NMR(376MHz,Chloroform-d)δ-109.04；HRMS(ESI+):C16H13F2O4 +[M+H]+307.0776,found 307.0772.
4'-氰基-3,5-二氟-[1,1'-联苯]-4-甲酸甲酯
112.90,111.41-110.56(m),110.46,52.91；19F NMR(376MHz,Chloroform-d)δ-108.46；HRMS(ESI+):calculated for C15H10F2NO2 +[M+H]+274.0674,found 274.0673.
4'-(N,N-二乙基磺酰胺基)-3,5-二氟-[1,1'-联苯]-4-甲酸甲酯
127.76,127.65,111.53-110.55(m),110.09(t,J＝17.9Hz),52.88,42.09,14.17；19F NMR(376MHz,Chloroform-d)δ-108.72；HRMS(ESI+):calculated for C18H19F2NNaO4S+[M+Na]+406.0895,found406.0890.
3,4',5-三氟-[1,1'-联苯]-4-甲酸甲酯
＝21.7Hz),110.63-110.11(m),109.09(t,J＝17.8Hz),52.89；19FNMR(376MHz,Chloroform-d)δ-109.31,-112.27；HRMS(ESI+):calculated for C14H10F3O2 +[M+H]+267.0627,found267.0623.
3'-氰基-3,5-二氟-[1,1'-联苯]-4-甲酸甲酯
J＝18.0Hz),52.92；19F NMR(376MHz,Chloroform-d)δ-108.40；HRMS(ESI+):C15H10F2NO2 +[M+H]+274.0674,found 274.0674.
3,3',5,5'-四氟-[1,1'-联苯]-4-甲酸甲酯
25.3Hz),52.89；19F NMR(376MHz,Chloroform-d)δ-108.22(t,J＝7.9Hz),-108.68(d,J＝9.1Hz)；HRMS(ESI+):calculated for C14H9F4O2 +[M+H]+285.0533,found 285.0533.
3,5-二氟-3'-甲氧基-[1,1'-联苯]-4,4'-二甲酸甲酯
Hz),142.86(t,J＝2.2Hz),132.48,120.45,118.80,111.03-110.60(m),110.57,109.90(t,J＝17.8Hz),56.16,52.81,52.16；19F NMR(376MHz,Chloroform-d)δ-109.04(d,J＝9.2Hz)；HRMS(ESI+):calculated for C17H14F2NaO5 +[M+Na]+359.0702,found 359.0696.
3',5'-二氟-2-甲基-[1,1'-联苯]-4,4'-二甲酸甲酯
Hz),141.20,140.92(t,J＝2.5Hz),131.49,130.22,130.05,124.24,111.12-110.24(m),109.73(t,J＝17.9Hz),52.81,52.01,21.88；19F NMR(376MHz,Chloroform-d)δ-109.17；HRMS(ESI+):calculated for C17H15F2O5 +[M+H]+321.0933,found 321.0931./>
3,5-二氟-4'-甲氧基-[1,1'-联苯]-4-甲酸甲酯
55.42,52.66；19F NMR(376MHz,Chloroform-d)δ-109.70；HRMS(ESI+):C15H13F2O3 +[M+H]+279.0827,found 279.0825.
2,6-二氟-4-(噻吩-2)-苯甲酸甲酯
109.22-108.79(m),108.58(t,J＝17.6Hz),52.72；19F NMR(376MHz,Chloroform-d)δ-109.18(d,J＝9.6Hz)；HRMS(ESI+):calculated for C12H9F2O2S+[M+H]+255.0286,found255.0286.
2,6-二氟-4-(吡啶-2)-苯甲酸甲酯
137.58,123.95,121.13,110.44(t,J＝18.9Hz),110.03-109.64(m),51.91；19F NMR(376MHz,Methanol-d4)δ-111.98；HRMS(ESI+):calculated for C13H10F2NO2 +[M+H]+250.0674,found250.0671.
4-己氧羰基-2,6-二氟苯甲酸甲酯
Hz),161.34,160.25(dd,J＝257.4,6.2Hz),135.02(t,J＝9.5Hz),114.66(t,J＝18.9Hz),113.55-112.62(m),66.30,53.07,31.39,28.50,25.60,22.51,13.97；19F NMR(376MHz,Chloroform-d)δ-109.08；HRMS(ESI+):calculated for C15H19F2O4 +[M+H]+301.1246,found301.1247.
4'-(1S,3S,4R)-3-异丙基-4-甲基环己基)-4-甲基-3,5-二氟-[1,1'-联苯]-4,4'-二甲酸二甲酯
1.54(m,2H),1.24-1.08(m,2H),1.00-0.92(m,7H),0.83(d,J＝6.9Hz,3H)；13C NMR(101MHz,Chloroform-d)δ162.07(t,J＝1.6Hz),161.10(dd,J＝256.3,7.1Hz),149.30,146.58(t,J＝10.3Hz),135.15(d,J＝2.3Hz),127.64,126.84,110.75-109.56(m),108.58(t,J＝17.7Hz),52.67,44.33,37.32,37.24,34.20,33.47,32.19,26.63,22.71,14.11；19F NMR(376MHz,Chloroform-d)δ-109.05；HRMS(ESI+):calculated for C25H29F2O4 +[M+H]+431.2028,found431.2028.
4'-(己基-3-烯-1-基)氧羰基-3,5-二氟-[1,1'-联苯]-4,4'-二甲酸二甲酯
性状：粘稠无色液体
(t,J＝1.5Hz),160.78(dd,J＝255.0,7.0Hz),161.65,145.20(t,J＝10.1Hz),141.65,134.93,134.15,130.67,130.63,129.84,126.86,124.06,123.62,110.92-109.98(m),109.63(t,J＝17.7Hz),64.50,64.42,51.90,31.73,26.39,25.29,20.16,13.25,12.82；19FNMR(376MHz,Methanol-d4)δ-111.48,-111.54；HRMS(ESI+):C21H20F2NaO4 +[M+Na]+397.1222,found397.1217.
3,5-二氟-4'-((1s,4r)-4-丙基环己基)-[1,1'-联苯]-4-甲酸甲酯
(m,4H),1.46(qd,J＝12.6,3.3Hz,2H),1.38-1.28(m,3H),1.26-1.16(m,2H),1.05(qd,J＝13.1,12.4,3.7Hz,2H),0.89(t,J＝7.2Hz,3H)；13C NMR(101MHz,Chloroform-d)δ162.09(t,J＝1.6Hz),161.10(dd,J＝256.2,7.0Hz),149.30,146.59(t,J＝10.3Hz),135.16(d,J＝2.3Hz),127.64,126.84,110.54-109.81(m),108.48(t,J＝17.7Hz),52.69,44.33,39.64,36.94,34.19,33.43,20.00,14.39；19F NMR(376MHz,Chloroform-d)δ-109.78(d,J＝10.0Hz)；HRMS(ESI+):calculated for C23H26F2NaO2 +[M+Na]+395.1793,found 395.1790.
3,5-二氟-4'-((1s,4r)-4-戊基环己基)-[1,1'-联苯]-4-甲酸甲酯
1.37-1.18(m,9H),1.06(tdd,J＝14.2,11.3,3.7Hz,2H),0.90(t,J＝6.9Hz,3H)；13C NMR(101MHz,Chloroform-d)δ162.07(t,J＝1.6Hz),161.10(dd,J＝256.3,7.1Hz),149.30,146.58(t,J＝10.3Hz),135.16(t,J＝2.3Hz),127.64,126.84,110.50-109.88(m),108.58(t,J＝17.7Hz),52.67,44.33,37.32,37.24,34.20,33.47,32.19,26.63,22.71,14.11；19FNMR(376MHz,Chloroform-d)δ-109.74；HRMS(ESI+):calculated for C25H30F2NaO2 +[M+Na]+423.2106,found 423.2102./>
2,3,5-三氟-4'-甲基-[1,1'-联苯]-4-甲酸甲酯
性状：白色固体
9.8,1.5Hz),129.95(dt,J＝3.2,1.8Hz),129.56,128.62(d,J＝3.4Hz),111.80(ddd,J＝24.7,3.8,2.1Hz),110.09(dd,J＝19.3,14.3Hz),52.95,21.27；19F NMR(376MHz,Chloroform-d)δ-115.70(dd,J＝15.1,10.2Hz),-132.89(d,J＝20.6Hz),-146.45(ddd,J＝20.6,14.8,5.4Hz)；HRMS(ESI+):calculated for C15H12F3O2 +[M+H]+281.0784,found281.0787.
2,3,5-三氟-4'-甲氧基-[1,1'-联苯]-4-甲酸甲酯
(ddd,J＝247.0,13.5,4.1Hz),133.77(t,J＝10.1Hz),130.09(d,J＝3.6Hz),125.08(dt,J＝3.0,1.8Hz),114.28,111.50(ddd,J＝24.8,3.7,2.2Hz),109.67(dd,J＝19.3,14.4Hz),55.35,52.92；19F NMR(376MHz,Chloroform-d)δ-115.69(d,J＝15.0Hz),-132.92(d,J＝20.3Hz),-146.71(dd,J＝20.4,15.0Hz)；HRMS(ESI+):calculated for C15H12F3O3 +[M+H]+297.0733,found 297.0733.
虽然结合实施例对本发明的具体实施方式进行了详细地描述，但不应理解为对本专利的保护范围的限定。在权利要求书所描述的范围内，本领域技术人员不经创造性劳动即可作出的各种修改和变形仍属本专利的保护范围。

Claims (3)

1.一种基于芳基碳氟键羧基化反应合成多氟芳基羧酸类化合物的方法，其特征在于，包括以下步骤：
将反应底物、光催化剂、氢原子转移试剂、还原剂和碱加入反应容器中，然后在CO2气氛下加入溶剂，在光照条件下，室温搅拌反应0.1~72 h，再分离、纯化，得多氟芳基羧酸类化合物；
所述反应底物的结构通式如式（I）~（III）所示：
，
其中，R1为如下取代基中的一种：
，
R4为tBu、SMe、cyclopropyl、OCF3或F；
R2为如下取代基中的一种：
，
R3为如下取代基中的一种：
；
所述光催化剂为Ir(ppy)2(dtbbpy)PF6；
所述还原剂为甲酸钾；
所述氢原子转移试剂为N,N-二甲基乙醇胺；
所述溶剂为DMF；
所述碱为CsF和Cs2CO3的混合物。
2.根据权利要求1所述的基于芳基碳氟键羧基化反应合成多氟芳基羧酸类化合物的方法，其特征在于：所述还原剂、反应底物、光催化剂、氢原子转移试剂和碱的摩尔比为1~5:1:0.001~0.2:0.01~2:1~10。
3. 根据权利要求1所述的基于芳基碳氟键羧基化反应合成多氟芳基羧酸类化合物的方法，其特征在于：所述反应容器中二氧化碳压力为0.1~30倍大气压；光源与反应容器间的距离为0.1~10 cm，光的波长为300~560 nm，光源功率为1~100 W。
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