CN115073250A - 一种基于sp3碳氟键羧基化反应合成α-芳基乙酸或α-氟代羧酸类化合物的方法 - Google Patents
一种基于sp3碳氟键羧基化反应合成α-芳基乙酸或α-氟代羧酸类化合物的方法 Download PDFInfo
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Abstract
本发明公开了一种基于sp3碳氟键羧基化反应合成α‑芳基乙酸或α‑氟代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、光催化剂和碱加入反应容器中,然后在CO2气氛下加入还原剂和溶剂,在可见光照射条件下,室温搅拌反应2~48h,对反应产物进行分离纯化,制得α‑芳基乙酸或α‑氟代羧酸类化合物。本发明方案具有反应条件温和、产物收率高、反应底物普适性广和原料廉价易得的特点,以高效且高选择性地实现C‑F键的断裂并引入重要的羧基官能团,制得重要的α‑芳基乙酸或α‑氟代羧酸类化合物,具有广泛的应用前景。
Description
技术领域
本发明涉及有机合成技术领域,具体涉及到一种基于sp3碳氟键羧基化反应合成α-芳基乙酸或α-氟代羧酸类化合物的方法。
背景技术
在现代有机合成技术领域,有机卤化物参与的交叉偶联反应已经成为合成复杂分子的重要方法。由于碳氟键在有机卤化物中具有最短的键长、最大的键解离能,且有机卤化物的反应活性与它们的键离解能成反比,因此,碳氟键是自然界中最强、最惰性的碳卤键,也更难以实现活化。另一方面,有机氟化物广泛存在于天然产物和药物分子中,且具有独特的化学与生物性质,在医药、农药以及材料等领域有着广泛的应用。因此,发展一种温和而高效的方法来合成部分含氟分子具有重要的意义。
二氧化碳作为无毒、大量存在且廉价易得的温室气体,在有机合成中是一种理想的碳一合成子。而且多氟化合物廉价易得、来源广泛,可与二氧化碳通过选择性碳氟键官能团化高效得到不易制备的重要的部分含氟分子。但这方面的研究一直鲜有报道,且已报道的工作均集中在相对较为活泼的sp2杂化碳上的碳氟键羧基化反应进行研究,如已有一例关于利用二氧化碳在可见光下的氟代烯烃的羧基化的报道,用于快速合成一系列氟代丙烯酸类化合物。科学家们更关注于多氟化合物的碳氟键选择性断裂,目前对于更为惰性的sp3杂化碳上的碳氟键选择性羧基化反应亟待开展。
发明内容
针对现有技术的不足或缺陷,本发明的目的是提供一种基于sp3碳氟键羧基化反应合成α-芳基乙酸或α-氟代羧酸类化合物的方法,可有效解决现有技术中针对更为惰性的sp3杂化碳上的碳氟键选择性羧基化研究空白的问题,同时该方法能够合成得到α-芳基乙酸或α-氟代羧酸类化合物,具有反应条件温和、产物收率高、反应底物普适性广和原料廉价易得的特点。
为达上述目的,本发明采取如下的技术方案:
本发明提供一种基于sp3碳氟键羧基化反应合成α-芳基乙酸或α-氟代羧酸类化合物的方法,具体包括以下步骤:
将反应底物、光催化剂和碱加入反应容器中,然后在CO2气氛下加入还原剂和溶剂,在可见光照射条件下,室温搅拌反应2~48h,对反应产物进行分离纯化,制得α-芳基乙酸或α-氟代羧酸类化合物;其中,还原剂、反应底物、光催化剂和碱的摩尔比为1~10:1:0.005~0.5:0.1~5;
反应底物为苄氟类化合物、二氟羧酸酯类化合物或二氟酰胺类化合物,其结构通式如下所示:
其中,R1为芳基、酯基或氨酰基;R2为氢原子、氟原子、烷基或芳基;R3为氢原子或氟原子。
进一步地,还原剂、反应底物、光催化剂和碱的摩尔比为2:1:0.02:0.5~2.5。
进一步地,二氧化碳压力为0.5-10倍大气压,溶剂浓度为0.05-1M,可见光的波长为400~560nm,可见光的光源距离为1~2cm,可见光的功率为1-100W,优选为30W。
进一步地,苄氟类化合物包括单氟取代的苄氟类化合物、二氟取代的苄氟类化合物或三氟取代的苄氟类化合物。
进一步地,单氟取代的苄氟类化合物包括有:
进一步地,二氟取代的苄氟类化合物包括有:
进一步地,三氟取代的苄氟类化合物包括有:
进一步地,二氟羧酸酯类化合物及二氟酰胺类化合物包括有:
进一步地,光催化剂为4CzIPN、3DPAFIPN、5CzBN、3DPA2FBN、4CzPN、4DPAIPN、Ir(dFCF3ppy)2(dtbbpy)PF6、Ir(ppy)2(dtbbpy)PF6或4CzBnBN,优选为4CzIPN。
进一步地,碱为Na2CO3、K2CO3、CsF、KOtBu、Cs2CO3、CsOAc、CsOPiv、KOMe、K3PO4、CF3CO2K、CF3CO2Cs、CsHCO3或Me3SiOK,优选为Cs2CO3。
进一步地,还原剂为Ph2MeSiH、PhMe2SiH、MeEt2SiH、(TMS)3SiH、iPr3SiH、Ph3SiH、Et3SiH、HBpin或PMHS(聚甲基氢硅氧烷),优选为Et3SiH。
进一步地,溶剂为超干溶剂,优选DMAc、DMSO或MeCN。
进一步地,当反应底物为部分二氟取代的苄氟类化合物或三氟取代的苄氟类化合物时,在碱性条件下,将所得反应产物与碘甲烷进行酯化反应,制得氟代羧酸酯类化合物。
本发明具有以下优点:
1、本发明提供了一种基于sp3碳氟键羧基化反应合成α-芳基乙酸或α-氟代羧酸类化合物的方法,在可见光催化下,具体以苄氟类化合物、二氟羧酸酯类化合物或二氟酰胺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、还原剂和碱,制得α-芳基乙酸或α-氟代羧酸类化合物;本方法具有反应条件温和、原料廉价易得的特点;
2、本发明提供的合成方法对于单氟、二氟、三氟取代及二氟羧酸酯、二氟酰胺类的底物均具有良好的反应性,具有反应底物普适性广和产物收率高的特点;
3、本发明首次实现了苄氟类化合物、二氟羧酸酯类化合物或二氟酰胺类化合物上sp3碳氟键的选择性羧基化反应,此反应高效且高选择性地实现C-F键的断裂并引入重要的羧基官能团,制得重要的α-氟代羧酸类等化合物,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
为了使本发明的目的、技术方案及优点更加清楚明白,以下结合实施例,对本发明进行进一步详细说明。应当理解,此处所描述的具体实施例仅用以解释本发明,并不用于限定本发明,即所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例。
实施例1
本实施例1提供一种通过二氟取代的苄氟类化合物的碳氟键羧基化合成α-氟代羧酸类化合物的方法,具体步骤如下:
取一个干燥的10ml Schlenk反应管(带搅拌子),准确称取光催化剂4CzIPN(3.2mg,0.004mmol,2mol%)和二氟取代的苄氟类化合物(0.2mmol,1.0equiv,若为非液体底物此时加入;若为液体底物则在加入溶剂之后通过注射器加入)加入反应管中,然后将反应管移至手套箱中加入Cs2CO3(33mg,0.1mmol,0.5equiv),之后使用反应管对应旋塞密封反应管,将其移出手套箱,用双排导气系统将反应管中气体置换为CO2,重复3次;紧接着在CO2氛围下使用注射器依次将超干溶剂DMSO(2ml)、三乙基硅烷(64μL,0.4mmol,2.0equiv)加入反应管中,加完后立刻在一个大气压CO2氛围下使用反应管对应的旋塞密封;将反应所用搅拌器转速调至1500r/min,反应管固定在水浴锅中,使用30W蓝色LED灯(波长为450nm左右)在1cm远处照射,并使用风扇持续冷却确保反应温度维持在25-30℃。搅拌反应4-36小时后,向反应混合物加入2ml乙酸乙酯稀释,再加入2ml 1N盐酸淬灭反应,然后搅拌3分钟,使用乙酸乙酯萃取反应液3次,合并有机相并使用旋蒸浓缩得粗产物,之后使用柱色谱分离纯化,纯化条件为:先用石油醚:乙酸乙酯=10:1(v:v)的混合溶液冲洗,再用石油醚:乙酸乙酯=5:1~1:1(v:v)并加0.1%醋酸的混合溶液洗脱,得到目标产物,具体反应结果见表1。
表1.以二氟取代的苄氟类化合物为底物及其所对应产物的收率
注:表1中a为反应条件如上述描述相同;b为使用3DPAFIPN替换4CzIPN,碳酸铯用量增至2当量;c为使用3DPAFIPN替换4CzIPN,碳酸铯用量增至2.5当量;d为克级反应,1i为7mmol,15h;e为以碘甲烷作甲酯化试剂的酯化分离收率。
上述实验结果表明,二氟取代的苄氟类化合物均以较高的产率与选择性得到α-氟代羧酸类化合物,并且在该反应体系下,合成得到许多具有生物活性的官能团的化合物,如酯基、醚键、氰基、氟原子等都可在该反应体系下进行反应。
实施例2
本实施例2提供一种通过三氟取代的苄氟类底物的碳氟键羧基化且进一步与碘甲烷进行酯化反应合成得到α,α-二氟代羧酸酯类化合物的方法,具体步骤如下:
取一个干燥的10ml Schlenk反应管(带搅拌子),称取光催化剂3DPAFIPN(2.6mg,0.004mmol,2mol%)和三氟取代的苄氟类底物(0.2mmol,1.0equiv,若为非液体底物此时加入;若为液体底物则在加入溶剂之后通过注射器加入)加入反应管中,然后将反应管移至手套箱中加入Cs2CO3(130mg,0.4mmo,2.0equiv),之后使用反应管对应旋塞密封反应管,将其移出手套箱,用双排导气系统将反应管中气体置换为CO2,重复3次;紧接着在CO2氛围下使用注射器依次将超干溶剂DMSO(2ml)、三乙基硅烷(64μL,0.4mmol,2.0equiv)加入反应管中,加完后立刻在一个大气压CO2氛围下使用反应管对应的旋塞密封,将反应所用搅拌器转速调至1500r/min,反应管固定在水浴锅中,使用30W蓝色LED灯(波长为450nm左右)在1cm远处照射,并使用风扇持续冷却确保反应温度维持在25℃。搅拌反应4.5-22小时后,向反应混合物加入2ml乙酸乙酯稀释,再加入2ml 1N盐酸淬灭反应,然后搅拌3分钟,使用乙酸乙酯萃取反应液3次,合并有机相并使用旋蒸浓缩得粗产物;再使用4ml丙酮将粗品转移到一个10mlschlenk管中,加入碳酸钾(138mg,1mmol,5.0equiv)和碘甲烷(62μL,1mmol,5.0equiv),之后于70℃温度下封管反应4h;反应完成后降至室温,加入4ml乙酸乙酯稀释反应液,使用玻璃漏斗过滤并用5ml乙酸乙酯洗涤,使用旋蒸浓缩滤液得到粗产物,之后使用柱色谱分离纯化得到产物,洗脱剂配比为:石油醚:二氯甲烷=5:1~3:1(v:v),具体反应结果见表2。
表2.以三氟取代的苄氟类化合物为底物及其所对应产物的收率。
注:表2中a为反应条件上述相同;b为使用4CzIPN替换3DPAFIPN,碳酸铯用量减至0.5当量;c为碳酸铯用量减至0.5当量,还原剂用量增至10当量;d为碳酸铯用量减至1.0当量,使用Ir(dFCF3ppy)2(dtbbpy)PF6替换3DPAFIPN。
以上实验结果可以发现,易得的三氟类底物也可以发生相应的碳氟键羧基化反应,虽然伴随一定的脱氟质子化的副反应,但也以中等产率得到目标产品,如硫烷基取代的3a快速反应得到目标产物,其他非活化底物如苯氧基、苯基取代都得到了目标产物。
实施例3
本实施例3提供一种通过单氟取代的苄氟类化合物的碳氟键羧基化合成α-芳基乙酸类化合物的方法,具体步骤如下:
取一个干燥的10ml Schlenk反应管(带搅拌子),称取光催化剂4CzIPN(3.2mg,0.04mmol,2mol%)和单氟取代的苄氟类底物(0.2mmol,1.0equiv,若为非液体底物此时加入;若为液体底物则在加入溶剂之后通过注射器加入)加入反应管中,然后将反应管移至手套箱中加入Cs2CO3(33mg,0.1mmol,0.5equiv),之后使用反应管对应旋塞密封反应管,将其移出手套箱,用双排导气系统将反应管中气体置换为CO2,重复3次;紧接着在CO2氛围下使用注射器依次将超干溶剂DMSO(2ml)、三乙基硅烷(64μL,0.4mmol,2.0equiv)加入反应管中,加完后立刻在一个大气压CO2氛围下使用反应管对应的旋塞密封(部分加压反应额外使用注射剂打入24mlCO2,并缠好密封带以防止CO2逸出);将反应所用搅拌器转速调至1500r/min,反应管固定在水浴锅中,使用30W蓝色LED灯在1cm远处照射,并使用风扇持续冷却确保反应温度维持在25℃。搅拌反应16h后,向反应混合物加入2ml乙酸乙酯稀释,再加入2ml 1N盐酸淬灭反应,然后搅拌3分钟,使用乙酸乙酯萃取反应液3次,合并有机相并使用旋蒸浓缩得粗产物。之后使用柱色谱分离纯化,纯化条件为:先用石油醚:乙酸乙酯=10:1(v:v)的混合溶液冲洗,再用石油醚:乙酸乙酯=5:1~1:1(v:v)并加0.1%醋酸的混合溶液洗脱,得到目标产物,具体反应结果见表3。
表3.以单氟取代的苄氟类化合物为底物及其所对应产物的收率
注:表3中a为反应条件与上述描述相同;b为在4个大气压CO2下进行反应;c为100W绿色LED灯(波长为550nm左右)照射下反应2h;d为使用3DPAFIPN代替4CzIPN,碳酸铯量增至2.0当量,光催化剂用量减至0.5mol%,反应36h;e为使用3DPAFIPN代替4CzIPN,光催化剂用量增至20mol%,碳酸铯量增至5当量,反应48h;f为反应12h;
上述实验数据表明,不同取代基取代的单氟类底物,吸电子基团具有非常好的收率。并且将CO2压强提升至4个大气压后部分底物产率有明显上升,一些给电子基团也有不错的收率,如甲基、甲氧基、叔丁基等在反应体系中也都有优异的兼容性。对于一些未活化的苄氟类底物,采用还原性更强的3DPAFIPN并且增大碱的用量和反应时间会有更高的收率。
实施例4
本实施例4提供一种通过二氟羧酸酯类化合物及二氟酰胺类化合物的碳氟键羧基化合成α-氟代羧酸类化合物的方法,具体步骤如下:
取一个干燥的10mlSchlenk反应管(带搅拌子),称取光催化剂3DPAFIPN(2.6mg,0.004mmol,2mol%)和二氟羧酸酯类化合物或二氟酰胺类化合物(0.2mmol,1.0equiv,若为非液体底物此时加入;若为液体底物则在加入溶剂之后通过注射器加入)加入反应管中,然后将反应管移至手套箱中加入Cs2CO3(130mg,0.4mmol,2.0equiv),之后使用反应管对应旋塞密封反应管,将其移出手套箱,用双排导气系统将反应管中气体置换为CO2,重复3次;紧接着在CO2氛围下使用注射器依次将超干溶剂DMSO(2ml)、三乙基硅烷(64μL,0.4mmol,2.0equiv)加入反应管中,加完后立刻在一个大气压CO2氛围下使用反应管对应的旋塞密封。将反应所用搅拌器转速调至1500r/min,反应管固定在水浴锅中,使用30W蓝色LED灯在1cm远处照射,并使用风扇持续冷却确保反应温度维持在25℃。搅拌反应16-40小时后,向反应混合物加入2ml乙酸乙酯稀释,再加入2ml 1N盐酸淬灭反应,然后搅拌3分钟,使用乙酸乙酯萃取反应液3次,合并有机相并使用旋蒸浓缩得粗产物;之后使用柱色谱分离纯化,纯化条件为:先用石油醚:乙酸乙酯=10:1(v:v)的混合溶液冲洗,再用石油醚:乙酸乙酯=5:1~1:1(v:v)并加0.1%醋酸的混合溶液洗脱,得到目标产物,具体反应结果见表4。
表4.以单氟取代的苄氟类化合物为底物及其所对应产物的收率
注:表4中a为反应条件与上述描述相同;b为碳酸铯用量增至2.5当量;c为产物构型Z/E=1/1.5。
由以上结果表明,除了苄基碳氟键外,二氟羧酸酯及二氟酰胺类底物的碳氟键也可以发生该类反应,说明本发明提供的合成方法的反应底物普适性广。
实验例1
本实验例1以4-(1,1-二氟乙基)苯甲酸甲酯作为反应底物,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),4CzIPN(2mol%,3.2mg),三乙基硅烷(64μL,0.4mmol,2.0equiv),Cs2CO3(33mg,0.1mmol,0.5equiv),超干溶剂DMSO(2ml),实验结果见表5。
反应方程式如下所示:
表5.以4-(1,1-二氟乙基)苯甲酸甲酯作为反应底物在不同反应条件下的产物收率
序号 | 反应条件改变情况 | 2a产率(%) |
1 | 无变化 | (76) |
2 | 无光照 | <5 |
3 | 无4CzIPN | 0 |
4 | N<sub>2</sub>代替CO<sub>2</sub> | 0 |
5 | 无Cs<sub>2</sub>CO<sub>3</sub> | 0 |
6 | 无Et<sub>3</sub>SiH | 17 |
7 | PMHS代替Et<sub>3</sub>SiH | 45 |
8 | DIPEA代替Et<sub>3</sub>SiH | 29 |
9 | K<sub>2</sub>CO<sub>3</sub>代替Cs<sub>2</sub>CO<sub>3</sub> | 44 |
10 | MeCN代替DMSO | 0 |
11 | DMAc代替DMSO | 0 |
注:表5中括号内为分离收率,其余为以4-三氟甲基苯甲醚为核磁氢谱内标的核磁收率。
由上表5数据结果看出,在本发明反应条件下产率高达76%,一系列控制实验表明,光催化剂、还原剂、碱、CO2都是不可缺少的,缺少任意一项均无法得到产物。当使用其他还原剂时,产率不仅下降副产物还大量生成,更换溶剂MeCN、DMAc时则反应直接无法发生。
另外,在现有实验研究结果的基础上,发明人提出反应机理,以三乙基硅烷作为还原剂,碳酸铯作为碱为例进行说明,如图1所示,首先,三乙基硅烷、碳酸铯、二氧化碳在该反应条件下形成甲酸铯和硅醇铯,硅醇铯与激发态的光敏剂经历单电子转移(SET)过程得到还原态的光敏剂与硅氧自由基物种,硅氧自由基物种随后与甲酸铯发生氢原子转移(HAT)过程得到三乙基硅醇和二氧化碳自由基阴离子;随后二氧化碳自由基阴离子通过单电子转移(SET)过程还原含氟底物,接着在二氧化碳及路易斯酸的协助下实现碳氟键的断裂得到三乙基氟硅烷、甲酸盐及苄基自由基;然后苄基自由基被还原态光敏剂通过单电子转移(SET)过程还原为苄基碳负离子,最后与二氧化碳反应生成相应的羧酸盐,经过酸化处理得到目标产物。
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:
2-氟-2-(4-(甲基氧羰氧基)苯基)丙酸
1H NMR(400MHz,CDCl3)δ8.09–8.03(m,2H),7.63–7.58(m,2H),3.93(s,3H),1.97(d,J=22.3Hz,3H);19F NMR(376MHz,CDCl3)δ-152.85;13C NMR(101MHz,CDCl3)δ174.98(d,J=27.7Hz),166.79,143.29(d,J=22.5Hz),130.67(d,J=1.1Hz),129.98(d,J=1.1Hz),124.92(d,J=8.9Hz),94.25(d,J=187.8Hz),52.52,24.78(d,J=23.7Hz).HRMS(ESI-):calcd for C11H10FO4 -[M-H]-225.0569,found 225.0561;calcd for C10H10FO2 -[M-CO2H]-181.0670,found 181.0674.
2-(4-联苯基)-2-氟丙酸
1H NMR(400MHz,CDCl3)δ7.66–7.54(m,6H),7.48–7.40(m,2H),7.41–7.32(m,1H),2.00(d,J=22.2Hz,3H);19F NMR(376MHz,CDCl3)δ-151.18;13C NMR(101MHz,CDCl3)δ176.02(d,J=28.1Hz),142.07(d,J=1.2Hz),140.39,137.37(d,J=22.8Hz),128.98,127.80,127.46(d,J=0.8Hz),127.29,125.35(d,J=8.3Hz),94.35(d,J=186.2Hz),24.59(d,J=23.6Hz).HRMS(ESI-):calcd for C15H12FO2 -[M-H]-243.0827,found 243.0829.
2-(4-氰基苯基)-2-氟丙酸
1H NMR(400MHz,CDCl3)δ7.73–7.64(m,4H),1.97(d,J=22.3Hz,3H);19F NMR(376MHz,CDCl3)δ-153.81;13C NMR(101MHz,CDCl3)δ174.51(d,J=27.3Hz),143.43(d,J=23.0Hz),132.57(d,J=1.5Hz),125.72(d,J=9.3Hz),118.24,113.11(d,J=1.4Hz),93.93(d,J=189.2Hz),24.88(d,J=23.7Hz).HRMS(ESI-):calcd for C9H7FN-[M-CO2H]-148.0568,found 148.0573.
2-氟-2-(2-萘)丙酸
1H NMR(400MHz,CDCl3)δ8.00(d,J=1.8Hz,1H),7.90–7.79(m,3H),7.61(dd,J=8.7,1.9Hz,1H),7.55–7.46(m,2H),2.06(d,J=22.3Hz,3H);19FNMR(376MHz,CDCl3)δ-150.94;13C NMR(101MHz,CDCl3)δ176.19(d,J=27.9Hz),135.70(d,J=22.5Hz),133.36(d,J=1.1Hz),132.92(d,J=0.7Hz),128.67(d,J=1.1Hz),128.56,127.75,126.97,126.74,124.23(d,J=9.4Hz),122.39(d,J=7.6Hz),94.55(d,J=186.5Hz),24.59(d,J=23.6Hz).HRMS(ESI-):calcd for C13H10FO2 -[M-H]-217.0670,found 217.0674.
2-(3-氰基苯基)-2-氟丙酸
1H NMR(400MHz,CDCl3)δ7.85–7.83(m,1H),7.79(dt,J=8.0,1.5Hz,1H),7.68(dt,J=7.7,1.4Hz,1H),7.54(t,J=7.9Hz,1H),1.98(d,J=22.3Hz,3H);19F NMR(376MHz,CDCl3)δ-153.63;13C NMR(101MHz,CDCl3)δ174.74(d,J=27.5Hz),140.10(d,J=23.4Hz),132.69,129.72(d,J=1.3Hz),129.31(d,J=8.8Hz),128.71(d,J=9.5Hz),118.28,113.10(d,J=1.6Hz),93.59(d,J=189.3Hz),24.86(d,J=23.6Hz).HRMS(ESI-):calcd forC10H7FNO2 -[M-H]-192.0466,found192.0465.
2-氟-2-(4-氟-3-苯氧基苯基)乙酸
1H NMR(400MHz,CDCl3)δ7.38–7.31(m,2H),7.26–7.21(m,2H),7.20–7.16(m,1H),7.15–7.10(m,1H),7.02–6.95(m,2H),5.74(d,J=47.1Hz,1H);19F NMR(376MHz,CDCl3)δ-128.49(d,J=3.3Hz),-179.82;13C NMR(101MHz,CDCl3)δ173.49(d,J=28.2Hz),156.74,156.33(d,J=2.2Hz),153.82(d,J=2.0Hz),144.56(d,J=12.0Hz),130.02,123.89,122.94(dd,J=7.3,6.5Hz),120.02(dd,J=6.3,1.9Hz),117.78,117.76(d,J=19.2Hz),87.93(d,J=188.1Hz).HRMS(ESI-):calcd for C14H9F2O3 -[M-H]-263.0525,found263.0529;calcd for C13H9F2O-[M-CO2H]-219.0627,found 219.0626.
2-氟-2-(4-苯氧基苯基)乙酸
1H NMR(400MHz,CDCl3)δ9.10(s,1H),7.46–7.41(m,2H),7.39–7.33(m,2H),7.19–7.12(m,1H),7.07–6.93(m,4H),5.79(d,J=47.4Hz,1H);19F NMR(376MHz,CDCl3)δ-177.66;13C NMR(101MHz,CDCl3)δ174.19(d,J=28.5Hz),159.23(d,J=2.4Hz),156.34,130.08,128.71(d,J=5.5Hz),127.89(d,J=21.1Hz),124.20,119.75,118.68,88.58(d,J=186.3Hz).HRMS(ESI-):calcd for C14H10FO3 -[M-H]-245.0619,found 245.0622.
2-氟-2--(4-(甲基氧羰氧基)苯基)乙酸
1H NMR(400MHz,CDCl3)δ9.02(s,1H),8.08(d,J=8.2Hz,2H),7.57(d,J=8.3Hz,2H),5.89(d,J=47.3Hz,1H),3.93(s,3H);19F NMR(376MHz,CDCl3)δ-184.50;13C NMR(101MHz,CDCl3)δ172.91(d,J=26.7Hz),166.67,138.17(d,J=20.4Hz),131.48(d,J=1.2Hz),130.22,126.49(d,J=6.6Hz),88.34(d,J=187.2Hz),52.60.HRMS(ESI-):calcdfor C9H8FO2 -[M-CO2H]-167.0514,found 167.0523.
2-(4-联苯基)-2-氟乙酸
1H NMR(400MHz,DMSO-d6)δ7.74(d,J=8.0Hz,2H),7.72–7.65(m,2H),7.59–7.53(m,2H),7.53–7.44(m,2H),7.43–7.36(m,1H),6.05(d,J=47.5Hz,1H);19F NMR(376MHz,DMSO-d6)δ-175.69;13C NMR(101MHz,DMSO-d6)δ169.75(d,J=27.3Hz),141.24(d,J=2.4Hz),139.44,134.14(d,J=20.1Hz),129.02,127.83,127.58(d,J=5.5Hz),127.08,126.82,88.49(d,J=180.7Hz).HRMS(ESI-):calcd for C14H10FO2 -[M-H]-229.0670,found229.0673.
2-氟-2-(4-(甲基氧硫羰氧基)苯基)乙酸
1H NMR(400MHz,Methanol-d4)δ8.06–7.98(m,2H),7.80–7.72(m,2H),6.04(d,J=47.5Hz,1H),3.14(s,3H);19F NMR(376MHz,Methanol-d4)δ-185.03;13C NMR(101MHz,Methanol-d4)δ171.01(d,J=26.2Hz),142.84(d,J=1.8Hz),142.41(d,J=20.5Hz),128.85,128.47(d,J=6.7Hz),89.58(d,J=184.5Hz),44.24.HRMS(ESI-):calcd forC8H8FO2S-[M-CO2H]-187.0235,found 187.0236.
2-(4-氰基苯基)-2-氟乙酸
1H NMR(400MHz,CDCl3)δ7.73(d,J=8.1Hz,2H),7.63(d,J=8.2Hz,2H),5.90(d,J=47.1Hz,1H);19F NMR(376MHz,CDCl3)δ-186.44;13C NMR(101MHz,CDCl3)δ171.98(d,J=27.1Hz),138.52(d,J=20.9Hz),132.76,127.04(d,J=7.0Hz),118.08,113.72(d,J=1.8Hz),87.92(d,J=189.5Hz).HRMS(ESI-):calcd for C8H5FN-[M-CO2H]-134.0412,found134.0416.
2-(5-(2,2-二氟)苯并-1,3-二氧杂环戊烯)-2-氟乙酸
1H NMR(400MHz,CDCl3)δ8.38(s,1H),7.25–7.20(m,2H),7.14–7.07(m,1H),5.79(d,J=46.9Hz,1H);19F NMR(376MHz,CDCl3)δ-184.50;13C NMR(101MHz,CDCl3)δ173.36(d,J=28.2Hz),144.91,144.21,131.75(t,J=256.8Hz),129.54(d,J=21.4Hz),122.80(d,J=6.8Hz),109.89,108.19(d,J=6.5Hz),88.17(d,J=188.8Hz).HRMS(ESI-):calcd forC9H4F3O4 -[M-H]-233.0067,found233.0069.
2-(4-联苯基)-2-氟己酸
1H NMR(400MHz,CDCl3)δ8.42(s,1H),7.63–7.53(m,6H),7.46–7.39(m,2H),7.38–7.32(m,1H),2.49–2.29(m,1H),2.28–2.10(m,1H),1.52–1.29(m,4H),0.90(t,J=7.0Hz,3H);19F NMR(376MHz,CDCl3)δ-164.46;13C NMR(101MHz,CDCl3)δ176.09(d,J=28.1Hz),141.79(d,J=0.8Hz),140.43,136.59(d,J=22.9Hz),128.97,127.75,127.38(d,J=1.1Hz),127.27,125.42(d,J=9.3Hz),96.91(d,J=189.8Hz),37.95(d,J=21.9Hz),25.29(d,J=2.9Hz),22.69,13.96.HRMS(ESI-):calcd for C18H18FO2 -[M-H]-285.1296,found285.1292;calcd for C17H18F-[M-CO2H]-241.1398,found 241.1403.
2-氟-2-二苯基乙酸甲酯(含少量2n’的混合物)
1H NMR(400MHz,CDCl3)δ7.47–7.44(m,1H),7.43–7.37(m,5H),7.37–7.29(m,3H),3.87(s,3H);19F NMR(376MHz,CDCl3)δ-141.74;13C NMR(101MHz,CDCl3)δ169.75(d,J=27.6Hz),140.36(d,J=23.5Hz),137.86(d,J=22.4Hz),134.55,129.72,129.46(d,J=2.2Hz),129.35(d,J=1.9Hz),128.65,127.20(d,J=7.7Hz),126.91(d,J=6.8Hz),125.23(d,J=7.0Hz),97.04(d,J=191.3Hz),53.47.HRMS(ESI+):calcd for C15H12ClFNaO2 +[M+Na]+301.0402,found 301.0404.
2-(3-氯苯)-2-氟-2-苯基乙酸甲酯(含少量2o’的混合物)
1H NMR(400MHz,CDCl3)δ7.47–7.44(m,1H),7.43–7.37(m,5H),7.37–7.29(m,3H),3.87(s,3H);19F NMR(376MHz,CDCl3)δ-141.74;13C NMR(101MHz,CDCl3)δ169.75(d,J=27.6Hz),140.36(d,J=23.5Hz),137.86(d,J=22.4Hz),134.55,129.72,129.46(d,J=2.2Hz),129.35(d,J=1.9Hz),128.65,127.20(d,J=7.7Hz),126.91(d,J=6.8Hz),125.23(d,J=7.0Hz),97.04(d,J=191.3Hz),53.47.HRMS(ESI+):calcd for C15H12ClFNaO2 +[M+Na]+301.0402,found 301.0404.
2-氟-2,2-二(4-氟苯)乙酸甲酯(含少量2p’的混合物)
1H NMR(400MHz,CDCl3)δ7.44–7.36(m,4H),7.13–7.02(m,4H),3.87(s,3H);19FNMR(376MHz,CDCl3)δ-112.13(d,J=3.4Hz),-138.65(t,J=3.4Hz);13C NMR(101MHz,CDCl3)δ170.00(d,J=28.0Hz),163.18(dd,J=249.2,2.5Hz),134.14(dd,J=23.2,3.3Hz),129.06(dd,J=8.5,6.8Hz),115.56(d,J=21.8Hz),96.84(d,J=190.7Hz),53.49.GC-MS(EI):calcd for C15H11F3O2 m/z 280.1found 280.0.
2-氟-2-(4-(甲基氧羰氧基)苯)-2-苯乙酸甲酯
1H NMR(400MHz,CDCl3)δ8.05(d,J=8.1Hz,2H),7.58(d,J=8.2Hz,2H),7.47–7.35(m,5H),3.92(s,3H);19F NMR(376MHz,CDCl3)δ-141.08;13C NMR(101MHz,CDCl3)δ173.28(d,J=28.7Hz),166.81,142.40(d,J=22.9Hz),137.32(d,J=22.3Hz),130.90(d,J=1.9Hz),129.74,129.68(d,J=2.3Hz),128.71,127.12(d,J=7.2Hz),127.03(d,J=6.6Hz),97.05(d,J=190.4Hz),52.55.HRMS(ESI-):calcd for C15H12FO2 -[M-CO2H]-243.0827,found243.0825.
2-(4-正丁硫基苯)-2,2-二氟乙酸甲酯
1H NMR(400MHz,CDCl3)δ7.49(d,J=8.3Hz,2H),7.32(d,J=8.3Hz,2H),3.85(s,3H),2.96(t,J=7.4Hz,2H),1.66(p,J=7.4Hz,2H),1.47(h,J=7.3Hz,2H),0.94(t,J=7.3Hz,3H);19F NMR(376MHz,CDCl3)δ-103.46;13C NMR(101MHz,CDCl3)δ164.79(t,J=36.1Hz),142.04(t,J=1.9Hz),129.30(t,J=25.9Hz),127.32,125.96(t,J=6.1Hz),113.48(t,J=252.0Hz),53.77,32.23,30.99,22.13,13.76.HRMS(ESI+):calcd forC13H17F2O2S+[M+H]+275.0912,found 275.0915.
2,2-二氟-2-(3-苯硫基苯基)乙酸甲酯
1H NMR(400MHz,CDCl3)δ7.52(s,1H),7.46–7.38(m,3H),7.37–7.30(m,5H),3.83(s,3H);19F NMR(376MHz,CDCl3)δ-103.71;13C NMR(101MHz,CDCl3)δ164.47(t,J=35.3Hz),138.30,133.84,133.70(t,J=25.6Hz),132.46,132.25(t,J=1.7Hz),129.62,129.55,128.17,126.60(t,J=6.3Hz),123.66(t,J=6.1Hz),113.11(t,J=252.6Hz),53.84.HRMS(ESI+):calcd for C15H13F2O2S+[M+H]+295.0599,found 295.0604.
2,2-二氟-2-(3-苯氧基苯基)乙酸甲酯
1H NMR(400MHz,CDCl3)δ7.43–7.34(m,3H),7.34–7.30(m,1H),7.27–7.24(m,1H),7.18–7.13(m,1H),7.12–7.07(m,1H),7.04–7.00(m,2H),3.85(s,3H);19F NMR(376MHz,CDCl3)δ-103.49;13C NMR(101MHz,CDCl3)δ164.56(t,J=35.4Hz),157.87,156.35,134.49(t,J=25.7Hz),130.32,130.10,124.16,121.01(t,J=1.6Hz),120.04(t,J=6.2Hz),119.44,115.76(t,J=6.4Hz),113.11(t,J=252.5Hz),53.84.HRMS(ESI+):calcd forC15H13F2O3 +[M+H]+279.0827,found 279.0848.
2-(4-联苯基)-2,2-二氟乙酸甲酯
1H NMR(400MHz,CDCl3)δ7.70–7.64(m,4H),7.61–7.56(m,2H),7.49–7.43(m,2H),7.41–7.36(m,1H),3.87(s,3H);19F NMR(376MHz,CDCl3)δ-103.46;13C NMR(101MHz,CDCl3)δ164.84(t,J=35.8Hz),144.18(t,J=1.8Hz),140.03,131.55(t,J=25.7Hz),129.07,128.18,127.55,127.38,126.08(t,J=6.1Hz),113.62(t,J=253.1Hz),53.83.GC-MS(EI):calcd for C15H12F2O2 m/z 262.1found 262.0.
2-(2-联苯基)-2,2-二氟乙酸甲酯
1H NMR(400MHz,CDCl3)δ7.85–7.79(m,1H),7.56–7.46(m,2H),7.41–7.34(m,3H),7.30–7.23(m,3H),3.44(s,3H);19F NMR(376MHz,CDCl3)δ-94.21;13C NMR(101MHz,CDCl3)δ164.04(t,J=34.1Hz),141.32(t,J=4.4Hz),138.96,131.55,131.06(t,J=23.2Hz),130.71(t,J=1.6Hz),130.03(t,J=1.4Hz),128.11,127.87,127.62,125.74(t,J=8.5Hz),113.29(t,J=249.5Hz),53.26.HRMS(ESI+):calcd for C15H12F2NaO2 +[M+Na]+285.0698,found 285.0694.
2-(3-联苯基)-2,2-二氟乙酸甲酯
1H NMR(400MHz,CDCl3)δ7.85–7.80(m,1H),7.72(d,J=7.6Hz,1H),7.64–7.55(m,3H),7.55–7.50(m,1H),7.49–7.42(m,2H),7.41–7.35(m,1H),3.86(s,3H);19F NMR(376MHz,CDCl3)δ-103.63;13C NMR(101MHz,CDCl3)δ164.81(t,J=35.6Hz),142.04,140.11,133.41(t,J=25.5Hz),129.92(t,J=1.6Hz),129.32,129.08,128.05,127.35,124.53–124.14(m,2C),113.58(t,J=252.1Hz),53.81.HRMS(ESI+):calcd for C15H12F2NaO2 +[M+Na]+285.0698,found 285.0696.
2-(3-正丁硫基苯)-2,2-二氟乙酸甲酯
1H NMR(400MHz,CDCl3)δ7.54–7.48(m,1H),7.44–7.32(m,3H),3.85(s,3H),2.96(t,J=7.4Hz,2H),1.69–1.60(m,2H),1.52–1.41(m,2H),0.93(t,J=7.3Hz,3H);19F NMR(376MHz,CDCl3)δ-103.95;13C NMR(101MHz,CDCl3)δ164.61(t,J=35.5Hz),138.80,133.45(t,J=25.5Hz),130.75(t,J=1.8Hz),129.19,124.90(t,J=6.3Hz),122.50(t,J=6.1Hz),113.26(t,J=252.5Hz),53.82,32.88,31.04,22.07,13.75.HRMS(ESI+):calcdfor C13H17F2O2S+[M+H]+275.0912,found 275.0917.
2,2-二氟-2-(2-(10-苯基)吩噻嗪)乙酸甲酯
1H NMR(400MHz,CDCl3)δ7.67–7.57(m,2H),7.56–7.46(m,1H),7.41–7.34(m,2H),7.08–6.94(m,3H),6.89–6.75(m,2H),6.35(d,J=1.7Hz,1H),6.19–6.12(m,1H),3.74(s,3H);19F NMR(376MHz,CDCl3)δ-103.67;13C NMR(101MHz,CDCl3)δ164.46(t,J=35.7Hz),144.72,143.82,140.36,131.40(t,J=25.2Hz),131.16,130.86,128.86,127.33,126.90,126.83,124.23(t,J=2.0Hz),123.07,119.46(t,J=6.2Hz),119.24,116.37,113.13(t,J=252.2Hz),112.40(t,J=6.5Hz),53.60.HRMS(ESI+):calcd for C21H16F2NO2S+[M+H]+384.0864,found 384.0861.
2-(4-联苯基)乙酸
1H NMR(400MHz,DMSO-d6)δ12.41(s,1H),7.70–7.58(m,4H),7.49–7.44(m,2H),7.41–7.31(m,3H),3.62(s,2H);13C NMR(101MHz,DMSO-d6)δ172.80,140.00,138.57,134.35,130.07,129.00,127.40,126.64,126.62,40.33.LRMS(ESI-):calcd for C14H11O2 -[M-H]-211.08,found 210.78.
2-(4-(甲基氧羰氧基)苯基)乙酸
1H NMR(400MHz,CDCl3)δ8.00(d,J=8.1Hz,2H),7.35(d,J=8.1Hz,2H),3.91(s,3H),3.70(s,2H);13C NMR(101MHz,CDCl3)δ176.91,166.99,138.48,130.05,129.61,129.38,52.30,41.07.LRMS(ESI-):calcd for C9H9O2 -[M-CO2H]-149.06,found 148.80.
2-(4-氰基苯基)乙酸
1H NMR(400MHz,DMSO-d6)δ12.53(s,1H),7.78(d,J=8.3Hz,2H),7.47(d,J=8.2Hz,2H),3.71(s,2H);13C NMR(101MHz,DMSO-d6)δ171.89,140.94,132.09,130.66,118.90,109.52,40.44.LRMS(ESI-):calcd for C9H6NO2 -[M-H]-160.04,found 159.64.
2-(4-(二乙基氮甲酰基)苯基)乙酸
1H NMR(400MHz,CDCl3)δ7.32–7.24(m,4H),3.61–3.49(m,4H),3.33–3.18(m,2H),1.29–1.20(m,3H),1.10(t,J=7.1Hz,3H);13C NMR(101MHz,CDCl3)δ174.63,171.93,135.59,135.03,129.40,126.59,43.60,41.26,39.70,14.22,12.87.HRMS(ESI-):calcdfor C12H16NO-[M-CO2H]-190.1237,found 190.1239.
2-萘乙酸
1H NMR(400MHz,CDCl3)δ7.83–7.77(m,3H),7.73(s,1H),7.49–7.43(m,2H),7.40(dd,J=8.4,1.7Hz,1H),3.81(s,2H);13C NMR(101MHz,CDCl3)δ177.70,133.51,132.67,130.84,128.47,128.32,127.82,127.80,127.44,126.38,126.09,41.32.LRMS(ESI-):calcd for C12H9O2 -[M-H]-185.06,found 184.80.
2-(4-氰基-2-氟苯基)乙酸
1H NMR(400MHz,DMSO-d6)δ12.66(s,1H),7.81(dd,J=9.7,1.5Hz,1H),7.68–7.64(m,1H),7.57(t,J=7.6Hz,1H),3.75(s,2H);19F NMR(376MHz,DMSO-d6)δ-114.27;13C NMR(101MHz,DMSO-d6)δ170.88,160.22(d,J=247.6Hz),133.39(d,J=5.0Hz),128.87(d,J=16.2Hz),128.58(d,J=3.8Hz),118.95(d,J=25.8Hz),117.71(d,J=2.9Hz),111.36(d,J=10.1Hz),34.36(d,J=2.3Hz).HRMS(ESI-):calcd for C9H5FNO2 -[M-H]-178.0310,found178.0306.
2-(3-氰基苯基)乙酸
1H NMR(400MHz,CDCl3)δ7.62–7.56(m,2H),7.55–7.51(m,1H),7.48–7.42(m,1H),3.70(s,2H);13C NMR(101MHz,CDCl3)δ176.40,134.73,134.13,133.12,131.29,129.59,118.60,112.90,40.46.LRMS(ESI-):calcd for C9H6NO2 -[M-H]-160.04,found 159.79.
2-(3-(甲基氧羰氧基)苯基)乙酸
1H NMR(400MHz,CDCl3)δ8.00–7.93(m,2H),7.51–7.46(m,1H),7.44–7.39(m,1H),3.91(s,3H),3.71(s,2H);13C NMR(101MHz,CDCl3)δ177.21,166.98,134.10,133.75,130.71,130.67,128.86,128.77,52.34,40.82.LRMS(ESI-):calcd for C10H9O4 -[M-H]-193.05,found 192.80.
2-(4-(2'-氰基)联苯基)乙酸
1H NMR(400MHz,Methanol-d4)δ7.86–7.77(m,1H),7.75–7.68(m,1H),7.61–7.55(m,1H),7.55–7.47(m,3H),7.47–7.40(m,2H),3.69(s,2H);13C NMR(101MHz,Methanol-d4)δ175.24,146.47,138.30,136.88,134.86,134.35,131.29,130.82,129.93,128.98,119.59,112.05,41.61.HRMS(ESI-):calcd for C14H10N-[M-CO2H]-192.0819,found 192.0815.
2-(4-(烯丙基氧羰氧基)苯基)乙酸
1H NMR(400MHz,CDCl3)δ8.08–8.00(m,2H),7.41–7.33(m,2H),6.10–5.97(m,1H),5.40(dq,J=17.2,1.5Hz,1H),5.29(dq,J=10.5,1.2Hz,1H),4.82(dt,J=5.6,1.4Hz,2H),3.71(s,2H);13C NMR(101MHz,CDCl3)δ176.56,166.11,138.59,132.32,130.13,129.62,129.46,118.38,65.73,41.08.HRMS(ESI-):calcd for C11H11O2 -[M-CO2H]-175.0765,found175.0767.
2-(3-甲氧基苯基)乙酸
1H NMR(400MHz,CDCl3)δ7.27–7.21(m,1H),6.91–6.78(m,3H),3.80(s,3H),3.62(s,2H);13C NMR(101MHz,CDCl3)δ177.97,159.81,134.74,129.77,121.84,115.15,112.99,55.34,41.22.LRMS(ESI-):calcd for C14H11O2 -[M-H]-165.05,found 164.79.
2-(4-叔丁基苯基)乙酸
1H NMR(400MHz,CDCl3)δ7.40–7.31(m,2H),7.24–7.19(m,2H),3.61(s,2H),1.31(s,9H);13C NMR(101MHz,CDCl3)δ178.19,150.34,130.33,129.15,125.74,40.68,34.62,31.46.LRMS(ESI-):calcd for C12H15O2 -[M-H]-191.11,found 190.89.
2-(3-(2-甲基)联苯基)乙酸
1H NMR(400MHz,CDCl3)δ7.44–7.37(m,2H),7.36–7.31(m,1H),7.31–7.27(m,2H),7.24–7.16(m,3H),3.76(s,2H),2.20(s,3H).;13C NMR(101MHz,CDCl3)δ177.65,143.14,142.28,134.67,132.85,129.72,129.64,129.50,128.18,126.96,125.79,39.68,17.08.HRMS(ESI-):calcd for C15H13O2 -[M-H]-225.0921,found 225.0918.
2-(4-(甲基氧羰氧基)苯基)丙酸
1H NMR(400MHz,CDCl3)δ8.06–7.94(m,2H),7.45–7.33(m,2H),3.91(s,3H),3.80(q,J=7.1Hz,1H),1.53(d,J=7.2Hz,3H);13C NMR(101MHz,CDCl3)δ179.78,166.99,144.95,130.14,129.42,127.85,52.29,45.48,18.15.LRMS(ESI-):calcd for C10H11O2 -[M-CO2H]-163.08,found 162.86.
2-(4-(2-氟)联苯基)丙酸
1H NMR(400MHz,CDCl3)δ7.55–7.49(m,2H),7.46–7.32(m,4H),7.20–7.12(m,2H),3.78(q,J=7.1Hz,1H),1.55(d,J=7.2Hz,3H);19F NMR(376MHz,CDCl3)δ-117.40;13C NMR(101MHz,CDCl3)δ180.33,159.79(d,J=248.5Hz),141.04(d,J=7.7Hz),135.52,131.02(d,J=3.9Hz),129.08(d,J=2.9Hz),128.59,128.27(d,J=13.6Hz),127.85,123.82(d,J=3.4Hz),115.50(d,J=23.8Hz),44.98,18.14.LRMS(ESI-):calcd for C15H12FO2 -[M-H]-243.08,found 243.00;calcd for C14H12F-[M-CO2H]-199.09,found 199.05.
2-(3-苯氧基苯基)丙酸
1H NMR(400MHz,CDCl3)δ7.29–7.15(m,3H),7.05–6.96(m,2H),6.95–6.90(m,3H),6.83–6.76(m,1H),3.63(q,J=7.2Hz,1H),1.42(d,J=7.2Hz,3H);13C NMR(101MHz,CDCl3)δ180.49,157.62,157.06,141.81,130.02,129.90,123.51,122.50,119.11,118.37,117.63,45.33,18.19.LRMS(ESI-):calcd for C15H13O3 -[M-H]-241.09,found 240.92.
2-氟-2-甲基-3-((2-(4-苯基)丁基)氧基)-3-氧代丙酸
1H NMR(400MHz,CDCl3)δ7.32–7.24(m,2H),7.22–7.12(m,3H),7.05(s,1H),5.10–4.98(m,1H),2.73–2.53(m,2H),2.06–1.94(m,1H),1.90–1.76(m,4H),1.30(d,J=6.3Hz,3H);19F NMR(376MHz,CDCl3)δ-157.27,-157.31;13C NMR(101MHz,CDCl3)δ171.24(d,J=26.0Hz),171.20(d,J=25.9Hz),166.18(d,J=25.2Hz),166.14(d,J=25.1Hz),141.08,141.06,128.64,128.62,128.44,128.43,126.22,126.20,92.32(d,J=195.3Hz),73.97,73.94,37.42,31.62,31.55,20.80(d,J=23.0Hz),20.73(d,J=23.2Hz),19.75,19.73.HRMS(ESI-):calcd for C13H16FO2 -[M-CO2H]-223.1134,found 223.1133.
2-氟-2-甲基-3-((2-(1-苯基-2-甲基)丙基)氧基)-3-氧代丙酸
1H NMR(400MHz,CDCl3)δ7.75(s,1H),7.31–7.20(m,3H),7.20–7.15(m,2H),3.06(s,2H),1.75(d,J=21.8Hz,3H),1.51(d,J=2.8Hz,6H);19F NMR(376MHz,CDCl3)δ-156.48;13C NMR(101MHz,CDCl3)δ171.72(d,J=26.2Hz),165.40(d,J=25.1Hz),136.33,130.73,128.15,126.87,92.41(d,J=195.4Hz),86.33,46.96,25.65,25.43,20.74(d,J=23.1Hz).HRMS(ESI-):calcd for C13H16FO2 -[M-CO2H]-223.1134,found 223.1133.
3-((1-(3,7-二甲基)-6-辛烯)氧基)-2-氟-2-甲基-3-氧代丙酸
1H NMR(400MHz,CDCl3)δ7.12(s,1H),5.08(ddt,J=8.5,5.6,1.4Hz,1H),4.35–4.24(m,2H),2.06–1.89(m,2H),1.83(d,J=21.8Hz,3H),1.79–1.65(m,4H),1.62–1.45(m,5H),1.38–1.30(m,1H),1.24–1.14(m,1H),0.92(d,J=6.4Hz,3H);19F NMR(376MHz,CDCl3)δ-157.47;13C NMR(101MHz,CDCl3)δ171.07(d,J=26.3Hz),166.55(d,J=25.2Hz),131.67,124.51,92.24(d,J=195.1Hz),65.70,36.99,35.20,29.49,25.83,25.46,20.89(d,J=23.1Hz),19.45,17.78.HRMS(ESI-):calcd for C13H22FO2 -[M-CO2H]-229.1604,found229.1604.
2-氟-2-甲基-3-((2-(2-(1-(4-甲基)-3-环己烯))丙基)氧基)-3-氧代丙酸
1H NMR(400MHz,CDCl3)δ8.46(s,1H),5.35(s,1H),2.09–1.88(m,4H),1.88–1.72(m,5H),1.64(s,3H),1.56–1.45(m,6H),1.36–1.27(m,1H);19F NMR(376MHz,CDCl3)δ-156.39,-156.46;13C NMR(101MHz,CDCl3)δ171.58(d,J=26.1Hz),171.57(d,J=26.1Hz),165.07(d,J=25.0Hz),134.01,133.97,119.99,119.96,92.36(d,J=195.0Hz),89.30,89.28,43.02,43.01,30.73,26.20,26.19,23.75,23.26,23.04,22.96,22.88,22.80,20.63(d,J=23.3Hz),20.61(d,J=23.2Hz).HRMS(ESI-):calcd for C14H20FO4 -[M-H]-271.1351,found 271.1340.
2-氟-3-(((1R,2S,5R)-1-(2-异丙基-5-甲基))氧基)-2-甲基-3-氧代丙酸
1H NMR(400MHz,CDCl3)δ9.58(s,1H),4.81(tt,J=11.0,3.8Hz,1H),2.02(dt,J=12.4,4.0Hz,1H),1.91–1.76(m,4H),1.75–1.66(m,2H),1.58–1.43(m,2H),1.13–1.00(m,2H),0.96–0.86(m,7H),0.75(d,J=6.9Hz,3H);19F NMR(376MHz,CDCl3)δ-157.33,-157.46;13C NMR(101MHz,CDCl3)δ171.98(d,J=26.2Hz),166.06(d,J=25.0Hz),166.02(d,J=25.0Hz),92.30(d,J=195.5Hz),92.27(d,J=195.4Hz),77.77,77.74,46.91,40.30,40.25,34.17,34.16,31.52,26.33,26.24,23.46,23.43,22.04,20.79(d,J=23.1Hz),20.78,20.75,20.72(d,J=23.1Hz),16.22,16.17.HRMS(ESI-):calcd for C13H22FO2 -[M-CO2H]-229.1604,found 229.1603.
(E)-3-((1-(3,7-二甲基)-2,6-辛二烯)氧基)-2-氟-2-甲基-3-氧代丙酸(Z/E=1/1.5)
1H NMR(400MHz,CDCl3)δ7.11(s,1H),5.40–5.31(m,1H),5.13–5.02(m,1H),4.82–4.67(m,2H),2.18–1.99(m,4H),1.83(d,J=21.9Hz,3H),1.75(d,J=21.9Hz,3H),1.68(s,3H),1.60(s,3H);19F NMR(376MHz,CDCl3)δ-157.44,-157.46;13C NMR(101MHz,CDCl3)δ171.16(d,J=26.0Hz),166.53(d,J=25.1Hz),144.41,144.33,132.55,132.12,123.66,123.50,117.88,117.02,92.28(d,J=195.6Hz),63.91,63.67,39.63,32.34,26.72,26.33,25.79,23.67,20.94(d,J=23.1Hz),17.82,17.79,16.66.HRMS(ESI-):calcd forC14H20FO4 -[M-H]-271.1351,found 271.1341;calcd for C13H20FO2 -[M-CO2H]-227.1447,found 227.1445.
3-(((3R,8R,9R,10S,13R,14R,17R)-3-(17-乙酰基-10,13-二甲基-2,3,4,7,8,9,10,11,12,13,14,15,16,17-十四氢-1H-环戊烯并[a]菲))氧基)-2-氟-2-甲基-3-氧代丙酸
1H NMR(400MHz,CDCl3)δ8.18(s,1H),5.40(d,J=3.9Hz,1H),4.82–4.69(m,1H),2.56(t,J=8.7Hz,1H),2.38(d,J=8.1Hz,2H),2.23–2.10(m,4H),2.08–1.96(m,2H),1.95–1.85(m,2H),1.82(d,J=21.9Hz,3H),1.75–1.55(m,5H),1.55–1.39(m,3H),1.29–1.11(m,3H),1.07–0.96(m,4H),0.63(s,3H);19F NMR(376MHz,CDCl3)δ-157.39,-157.43;13C NMR(101MHz,CDCl3)δ211.47,170.53(d,J=25.9Hz),170.50(d,J=25.9Hz),166.05(d,J=25.0Hz),166.02(d,J=24.9Hz),139.04,139.03,123.06,92.27(d,J=195.1Hz),92.26(d,J=195.1Hz),76.72,63.79,56.84,49.81,44.33,38.77,37.60,37.58,36.88,36.66,36.65,31.87,31.85,31.72,31.71,27.36,27.33,24.60,22.95,21.12,20.81(d,J=22.9Hz),20.81(d,J=23.2Hz),19.42,13.36.HRMS(ESI-):calcd for C25H34FO5 -[M-H]-433.2396,found 433.2395.
2-氟-2-甲基-3-(((1R,2R,4R)2-(1,7,7-三甲基二环[2,2,1]庚基))氧基)-3-氧代丙酸
1H NMR(400MHz,CDCl3)δ7.54(s,1H),4.82–4.74(m,1H),1.86–1.67(m,7H),1.58(td,J=12.0,11.3,3.6Hz,1H),1.20–1.06(m,2H),0.94(d,J=2.1Hz,3H),0.85(d,J=4.0Hz,6H);19F NMR(376MHz,CDCl3)δ-157.37,-157.51;13C NMR(101MHz,CDCl3)δ171.81(d,J=26.2Hz),165.85(d,J=25.6Hz),165.78(d,J=25.6Hz),92.20(d,J=194.7Hz),92.17(d,J=194.0Hz),84.04,84.02,49.24,49.20,47.11,47.10,45.01,45.01,38.47,38.38,33.55,33.54,27.02,20.72(d,J=23.1Hz),20.71(d,J=23.1Hz),20.13,19.64,19.61,11.33,11.26.HRMS(ESI-):calcd for C13H20FO2 -[M-CO2H]-227.1447,found 227.1446.
3-(二苯基氮基)-2-氟-2-甲基-3-氧代丙酸
1H NMR(400MHz,CDCl3)δ8.99(s,1H),7.42–7.22(m,10H),1.85(d,J=22.3Hz,3H).;19F NMR(376MHz,CDCl3)δ-148.15;13C NMR(101MHz,CDCl3)δ172.20(d,J=25.2Hz),166.25(d,J=21.3Hz),129.37,122.37,93.63(d,J=202.4Hz),23.15(d,J=23.9Hz).HRMS(ESI-):calcd for C15H13FNO-[M-CO2H]-242.0981,found 242.0988.
3-(二(4-甲氧基苯基)氮基)-2-氟-2-甲基-3-氧代丙酸
1H NMR(400MHz,CDCl3)δ7.73(s,1H),7.28–7.14(m,4H),6.90–6.74(m,4H),3.76(s,6H),1.83(d,J=22.4Hz,3H);19F NMR(376MHz,CDCl3)δ-147.62;13C NMR(101MHz,CDCl3)δ172.21(d,J=25.3Hz),166.23(d,J=20.9Hz),159.65,158.24,136.03,132.79,131.03,127.41,114.45,114.42,93.38(d,J=199.4Hz),55.54,22.91(d,J=24.0Hz).HRMS(ESI-):calcd for C17H17FNO3 -[M-CO2H]-302.1198,found 302.1197.
2-氟-2-甲基-3-(甲基苯基氨基)-3-氧代丙酸
1H NMR(400MHz,CDCl3)δ8.89(s,1H),7.41–7.32(m,3H),7.26–7.20(m,2H),3.33(s,3H),1.78(d,J=22.0Hz,3H);19F NMR(376MHz,CDCl3)δ-148.92;13C NMR(101MHz,CDCl3)δ171.84(d,J=25.4Hz),166.44(d,J=20.8Hz),141.39,129.44,128.89,128.24,93.24(d,J=201.6Hz),40.29,23.21(d,J=23.7Hz).HRMS(ESI+):calcd for C11H13FNO3 +[M+H]+226.0874,found 226.0872.
以上内容仅仅是对本发明内容所作的举例和说明,所属本领域的技术人员不经创造性劳动即对所描述的具体实施例做的修改或补充或采用类似的方式替代仍属本专利的保护范围。
Claims (10)
2.如权利要求1所述的基于sp3碳氟键羧基化反应合成α-芳基乙酸或α-氟代羧酸类化合物的方法,其特征在于,所述还原剂、反应底物、光催化剂和碱的摩尔比为2:1:0.02:0.5~2.5。
3.如权利要求1或2所述的基于sp3碳氟键羧基化反应合成α-芳基乙酸或α-氟代羧酸类化合物的方法,其特征在于,所述二氧化碳压力为0.5-10倍大气压,所述溶剂浓度为0.05-1M,所述可见光的功率为1-100W,所述可见光的波长为400~560nm,所述可见光的光源距离为1~2cm。
4.如权利要求1或2所述的基于sp3碳氟键羧基化反应合成α-芳基乙酸或α-氟代羧酸类化合物的方法,其特征在于,所述苄氟类化合物包括单氟取代的苄氟类化合物、二氟取代的苄氟类化合物或三氟取代的苄氟类化合物。
5.如权利要求1或2所述的基于sp3碳氟键羧基化反应合成α-芳基乙酸或α-氟代羧酸类化合物的方法,其特征在于,所述光催化剂为4CzIPN、3DPAFIPN、5CzBN、3DPA2FBN、4CzPN、4DPAIPN、Ir(dFCF3ppy)2(dtbbpy)PF6、Ir(ppy)2(dtbbpy)PF6或4CzBnBN。
6.如权利要求1或2所述的基于sp3碳氟键羧基化反应合成α-芳基乙酸或α-氟代羧酸类化合物的方法,其特征在于,所述碱为Na2CO3、K2CO3、CsF、KOtBu、Cs2CO3、CsOAc、CsOPiv、KOMe、K3PO4、CF3CO2K、CF3CO2Cs、CsHCO3或Me3SiOK。
7.如权利要求1或2所述的基于sp3碳氟键羧基化反应合成α-芳基乙酸或α-氟代羧酸类化合物的方法,其特征在于,所述还原剂为Ph2MeSiH、PhMe2SiH、MeEt2SiH、(TMS)3SiH、iPr3SiH、Ph3SiH、Et3SiH、HBpin或聚甲基氢硅氧烷。
8.如权利要求1所述的基于sp3碳氟键羧基化反应合成α-芳基乙酸或α-氟代羧酸类化合物的方法,其特征在于,所述溶剂为超干溶剂。
9.如权利要求1或8所述的基于sp3碳氟键羧基化反应合成α-芳基乙酸或α-氟代羧酸类化合物的方法,其特征在于,所述溶剂为DMAc、DMSO或MeCN。
10.如权利要求1所述的基于sp3碳氟键羧基化反应合成α-芳基乙酸或α-氟代羧酸类化合物的方法,其特征在于,当反应底物为部分二氟取代的苄氟类化合物或三氟取代的苄氟类化合物,在碱性条件下,将所得反应产物与碘甲烷进行酯化反应,制得氟代羧酸酯类化合物。
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