CN113444005A - 一种双芳基取代的非活化烯烃合成新型戊二酸类化合物的方法 - Google Patents

一种双芳基取代的非活化烯烃合成新型戊二酸类化合物的方法 Download PDF

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CN113444005A
CN113444005A CN202110845308.6A CN202110845308A CN113444005A CN 113444005 A CN113444005 A CN 113444005A CN 202110845308 A CN202110845308 A CN 202110845308A CN 113444005 A CN113444005 A CN 113444005A
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余达刚
于博
肖汉至
李茜茜
颜思顺
鲍莹
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Qingdao Sanli Bennuo New Materials Ltd By Share Ltd
Sichuan University
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Abstract

本发明公开了一种双芳基取代的非活化烯烃合成新型戊二酸类化合物的方法，属于有机合成技术领域。本发明合成方法将双芳基取代的非活化烯烃反应底物、光敏剂、还原剂、碱加入反应容器中，然后在CO2氛围下加入攫氢试剂和溶剂，在可见光照射条件下，室温搅拌0.2～48h，反应完成后，对反应体系进行酸化淬灭处理，对反应产物进行分离纯化，制得新型戊二酸类产物。本发明合成方法具有反应条件温和、产物收率高、底物适用范围广、官能团兼容性较好等特点，并且二酸产物具有潜在应用价值，是一种环境友好和高效的合成复杂结构二酸化合物的策略。

Description

一种双芳基取代的非活化烯烃合成新型戊二酸类化合物的 方法
技术领域
本发明属于有机合成技术领域，具体涉及到一种双芳基取代的非活化烯烃底物在可见光驱动下通过芳基迁移策略构建新型戊二酸类化合物的方法。
背景技术
高度功能化的二酸合成在药物、有机合成和高聚物合成中具有重要意义，特别是作为合成聚酯和聚酰胺的单体，目前在工业上已得到了广泛的大规模应用。对于二酸的制备，传统的方法主要是用硝酸选择性氧化醇、环己醇和环己酮。但是，氧化过程中温室气体一氧化二氮(N2O)的生成违背了绿色化学的准则，并且用这种方法仅局限于制备对称二酸。尽管过渡金属催化的二烯或烯丙醇二羰基化是生成二酸的另一种方法，但是往往需要使用昂贵的金属催化剂。针对二酸的合成重要性及当前主要合成方法的局限性，亟待发展一种环境友好和高效的策略来合成复杂结构的二酸化合物。
近年来，二氧化碳作为一种廉价易得、无毒可再生、储量丰富的碳一资源，受到有机合成、材料、化学化工领域的极大关注。因此，发展高效的CO2转化方法兼具重要的学术意义和潜在的工业价值。最近，利用CO2参与羧酸构建受到了有机化学家们的高度重视，尤其是CO2参与烯烃的羧基化已成为构建羧酸产物的重要途径之一。尽管目前CO2参与的烯烃双羧基化已有部分报道，但是底物范围大多局限于活化烯烃。迄今为止，以可见光驱动的CO2参与非活化烯烃的双羧基化来构建新型二酸化合物的方法仍未有报道。因此，开发一种利用可见光促进CO2参与非活化烯烃的双羧基化高效构建新型戊二酸类化合物的方法是该领域亟需解决的重要问题。
发明内容
本发明为解决上述现有技术存在的问题，提供了一种双芳基取代的非活化烯烃合成新型戊二酸类化合物的方法，包括以下步骤：将反应底物、光敏剂、还原剂、碱加入反应容器中，然后在CO2氛围下加入攫氢试剂和溶剂，在可见光照射条件下，室温搅拌0.2-48h，对反应产物进行分离纯化，制得新型戊二酸类产物，其中反应底物为双芳基取代的非活化烯烃类底物，其结构通式如下所示：
Figure BDA0003180314680000011
其中R1为酰基，R2、R3各自独立的为H或烷基，Ar1、Ar2各自独立的为芳基或杂芳基。
进一步的，上述还原剂、攫氢试剂、光敏剂、反应底物和碱的摩尔比为(1～10):(0.1～1):(0.001～0.5):1:(1～5)。优选的，还原剂、攫氢试剂、光敏剂、反应底物和碱的摩尔比为为2:0.2:0.02:1:(1～3)。
进一步的，上述还原剂为采用氢硅烷类还原剂，优选为HSiEt3、HSi(nPr)3、HSi(CH2)5Me、HSi(OMe)3、HSi(OEt)3、HSiEt2Me、HSiEtMe2、HSi(OMe)2Me、HSi(OEt)2Me、HSiCl3、Me2ClSiH、Ph2SiH2、Ph3SiH、PhSiH3、Ph2MeSiH、Ph2ClSiH、PhMe2SiH、(TMS)3SiH、iPr3SiH或PMHS。
进一步的，上述攫氢试剂采用硫醇盐、硫酚盐、醇盐、硅醇盐、酚盐以及它们相应的盐或胺类，优选为iPr3SiSH、Ph3SiSH、CH3OOCCH2SH、MeCOSH、MeCOSK、PhCOSH、CF3C6H4SH、BnSH、PhSH、CF3CH2SH、(CH2SH)2、Me2CHCHMeSH、CySH、EtOH、PrOH、Me2CHCH2OH、Ph(CH2)2OH、CF3(CH2)2SH、tBuSH、tBuOOH、Ph3SiOH、或Quinuclidin-3-yl acetate。
进一步的，上述光敏剂采用有机染料光敏剂或金属络合物光敏剂，优选为4CzIPN、4CzIPN-Ph、4CzIPN-MeO、4CzIPN-Bu、4DPAIPN、3DPA2FBN、3DPAFIPN、5CzBN、DPZ、4CzPN、4CzPN-Ph、4CzPN-Bu、4CzTPN、4CzTPN-Bu、4DPAIPN、4FEIPN、DE-TMOA、TMOAQ、fac-Ir(ppy)3、fac-Ir(dF(ppy)3)、Ir(ppy)2(bpy)PF6、Ir(dFCF3ppy)2(dtbbpy)PF6或Ir(ppy)2(dtbbpy)PF6。
进一步的，上述碱为采用碳酸盐、碳酸氢盐、甲酸盐、羧酸盐、磷酸盐、烷氧基碱、氟化物、有机胺或硅氧基碱，优选为Cs2CO3、K2CO3、Na2CO3、HCOOK、HCOONa、HCOOCs、KOtBu、NaOtBu、CsOtBu、CsF、KF、NaF、DBN、DBU、iPr2EtN、Et3N、CsOAc、KOAc、NaOAc、CsOPiv、KOPiv、KOMe、NaOMe、K3PO4、Na3PO4、Cs3PO4、CF3CO2K、CF3CO2Cs、KHCO3、NaHCO3、CsHCO3或Me3SiOK。
进一步的，上述溶剂为DMSO、DMF、CH3CN、CH2Cl2、THF、Acetone、1,4-dioxiane、MeOH、NMP或DMAc。优选的，反应体系中溶剂浓度为0.01-1M。优选的，上述溶剂采用超干溶剂。
进一步的，上述二氧化碳压力为0.1-50倍大气压；上述可见光的功率为1-100W，上述可见光的波长为350～560nm，上述可见光的光源距离为0.1～5cm。
进一步的，上述双芳基取代的非活化烯烃类底物为对称芳基取代物或不对称芳基取代物。
进一步的，R1为甲酰基、乙酰基、丁酰基、戊酰基、己酰基、丙酰基、苯甲酰基、苯乙酰基、苯丙酰基、苯丁酰基、苯戊酰基、苯己酰基、溴苯甲酰基、氯苯甲酰基、氟苯甲酰基、三氟甲基苯甲酰基、萘酰基、联苯酰基、甲基苯甲酰基、吡啶酰基、噻吩酰基或呋喃酰基。
进一步的，R2、R3中的烷基为甲基、乙基、丙基、丁基、戊基、己基、庚基、辛基、壬基或癸基。
进一步的，芳基或杂芳基为苯基、甲苯基、乙苯基、丙苯基、丁苯基、戊苯基、己苯基、二乙基胺酰基苯基、二甲基胺酰基苯基、羧基苯基、酯基苯基、苯氧基苯基、乙氧苯基、甲氧苯基、三氟甲苯基、三氟甲氧苯基、氯苯基、氟苯基、溴苯基、联苯基、萘基、吡啶基、呋喃基或噻吩基。
进一步的，上述非活化烯烃类底物包括：
Figure BDA0003180314680000031
Figure BDA0003180314680000041
Figure BDA0003180314680000051
本发明反应机理如下：
以三苯基硅烷作为还原剂，三异丙基硅硫醇作为攫氢试剂、碳酸铯作碱为例进行说明，如图1所示。攫氢试剂在碱的作用下去质子化，生成的三异丙基硅硫负离子可以淬灭单线态激发的光敏剂发生单电子转移过程(SET)，得到还原态的光敏剂与三异丙基硅硫自由基。随后，三异丙基硅硫自由基通过氢原子转移过程(HAT),攫取体系中由三苯基硅烷与二氧化碳原位生成的甲酸盐氢原子产生关键的二氧化碳自由基负离子中间体。双芳基取代的非活化烯烃捕获二氧化碳自由基负离子，接着发生分子内1,2-芳基迁移后得到苄基自由基，随后在还原态光敏剂作用下苄基自由基被还原为苄基碳负离子同时伴随光敏剂重生回到基态。接着该碳负离子对于另一分子二氧化碳亲核进攻得到二羧酸盐，最后在盐酸淬灭反应后得到相应新型戊二酸产物。
本发明的有益效果：
1.本发明提供了一种双芳基取代的非活化烯烃底物在可见光驱动下通过芳基迁移策略构建新型戊二酸类化合物的方法，具体为在可见光催化下，以双芳基取代的非活化烯烃类化合物作为反应底物，二氧化碳作为羧基源，同时加入光催化剂、还原剂、攫氢试剂和碱，制得新型戊二酸类化合物，本方法具有反应条件温和、底物适用范围广、产物收率高等特点，并且产物存在潜在应用价值，因而具有广泛的应用前景；
2.本发明提供的合成方法对于不同双芳基取代的非活化烯烃类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.本发明实现了双芳基取代的非活化烯烃的双羧基化反应，此反应可高效地合成新型戊二酸类产物，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
实施例1
本实施例提供不同胺基取代的非活化烯烃化合物通过芳基迁移策略构建新型戊二酸类化合物的方法，具体步骤如下：
在烘干的10mL Schlenk管(带搅拌子)中，准确称取不同胺基取代的非活化烯烃化合物(0.2mmol,1.0equiv)、还原剂三苯基硅烷(104mg,0.4mmol,2.0equiv)，光敏剂3DPA2FBN(2.6mg,2mol％)加入反应管中，然后将反应管移至手套箱中加入碱Cs2CO3(196mg,0.6mmol,3.0equiv)，此后使用反应管对应旋塞密封反应管并移出手套箱。在双排导气系统下将反应管中气体置换为CO2氛围，重复3次；随后在CO2氛围下使用注射器依次加入攫氢试剂三异丙基硅硫醇(9μL，0.04mmol,20mol％)，超干溶剂DMSO(2mL)至反应管中，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1400r/min，反应管固定在水浴锅中，使用30W蓝色LED灯(波长450nm左右)在1-2cm处照射，并使用风扇持续制冷确保反应温度维持在25-30℃。搅拌反应24小时后，向反应混合物中加入4.5mL水和2mL乙酸乙酯稀释，再加入0.5mL 2N盐酸淬灭反应，使用乙酸乙酯萃取反应液4-6次，合并有机相后使用旋转蒸发仪浓缩得粗产品，之后采用柱色谱分离纯化，纯化条件为：石油醚/乙酸乙酯＝1：1(v:v)的混合溶液洗脱，再使用石油醚：乙酸乙酯＝1：1～1：3外加0.1-0.3％的醋酸混合溶液洗脱，得到目标产物，产物具体结构、产率及非对映体比例见表1，合成路线如下式所示。
Figure BDA0003180314680000071
表1不同胺基取代的双芳基非活化烯烃化合物对应产物及其收率、非对映体比例
Figure BDA0003180314680000072
实施例2
本实施例提供由对称双芳基取代的非活化烯烃类化合物构建新型戊二酸类化合物的方法，反应步骤与实施例1的反应步骤一致，仅为反应底物不同，产物具体结构、产率及非对映体比例如表2，具体反应式如下式所示。
Figure BDA0003180314680000073
表2不同对称双芳基取代的非活化烯烃类化合物对应产物及其收率、非对映体比例
Figure BDA0003180314680000081
实施例3
本实施例提供由不对称双芳基取代的非活化烯烃类化合物构建新型戊二酸类化合物的方法，反应步骤与实施例1的反应步骤一致，仅为反应底物不同，产物具体结构、产率及非对映体比例如表3，具体反应式如下式所示。
Figure BDA0003180314680000082
表3不同不对称双芳基取代的非活化烯烃类化合物对应产物及其收率、非对映体比例
Figure BDA0003180314680000091
上述实验结果表明，不同胺基取代、对称芳基取代、不对称芳基取代类的非活化烯烃底物均能以较高的产率与区域选择性以及适中至较好的非对映选择性得到新型戊二酸类化合物。在该反应体系下，可以兼容不同电性的底物如三氟甲基取代芳基、甲氧基取代芳基等，并且对于杂环取代芳基以及稠环取代芳基均可以获得较高的收率和区域选择性以及适中的非对映选择性获得产物，说明本发明提供的合成方法的反应底物普适性广并且选择性良好。
反应条件实验例
本实验例以N-(1,1-二苯基烯丙基)苯甲酰胺作为反应底物，通过改变反应条件，考察不同反应条件下对反应产率的影响，基础反应条件：1a底物(0.2mmol,1.0equiv)，3DPA2FBN(2mol％,2.6mg)，三苯基硅烷(Ph3SiH)(104mg,0.4mmol,2.0equiv)，三异丙基硅硫醇(iPr3SiSH)(9μL,20mol％)，Cs2CO3(196mg,3.0equiv)，超干溶剂DMSO(2mL)，实验结果见表4，反应方程式如下式所示。
Figure BDA0003180314680000101
表4以N-(1,1-二苯基烯丙基)苯甲酰胺作为反应底物在不同反应条件下的产物收率
Figure BDA0003180314680000102
注：表4中括号内为以二溴甲烷为核磁氢谱内标的核磁收率，其余均为分离收率。
由上表4数据可得，在本发明反应条件下分离产率高达90％，一系列控制实验表明，光催化剂、光、还原剂、碱、CO2都是不可缺少的，缺少任意一项时都无法获得产物。当使用其他攫氢试剂或不加攫氢试剂时，产率下降，说明攫氢试剂在其中起到促进作用；当使用其他还原剂时，产率同样下降；更换支持溶剂DMF、MeCN时，产率大幅下降甚至无法发生。
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-苯甲酰胺-2，3-二苯基戊二酸(2a)
Figure BDA0003180314680000111
72.5mg,90％yield,白色固体,dr＝10:1；
1H NMR(400MHz,(CD3)2CO)δ7.78(s,1H),7.74–7.68(m,2H),7.63–7.56(m,2H),7.55–7.49(m,1H),7.47–7.40(m,2H),7.37–7.24(m,5H),7.23–7.17(m,3H),4.90(dd,J＝10.9,3.1Hz,1H),3.21(dd,J＝17.0,3.2Hz,1H),3.09(dd,J＝17.0,10.9Hz,1H).
13C NMR(101MHz,CD3OD)δ173.47,173.06,167.13,139.79,139.21,135.70,132.40,130.31,129.33,128.76,128.63,128.47,128.38,128.13,127.85,69.83,47.10,37.23.
HRMS(m/z):Calcd for C24H20NO5 -[M-H]-:402.1347；Found:402.1344.
2-乙酰胺-2，3-二苯基戊二酸(2b)
Figure BDA0003180314680000112
33.4mg,49％yield,白色固体,dr＝4:1；
1H NMR(400MHz,CD3OD)δ7.45–7.31(m,3H),7.30–7.22(m,3H),7.20–7.14(m,3H),7.13–7.06(m,2H),4.60(dd,J＝11.7,2.8Hz,1H),3.18(dd,J＝16.5,2.8Hz,1H),2.81(dd,J＝16.5,11.7Hz,1H),1.95(s,3H).
13C NMR(101MHz,CD3OD)δ174.60,173.01,170.87,138.76,129.26,127.65,127.39,127.29,127.12,126.98,126.71,71.38,46.31,36.78,21.76.
HRMS(m/z):Calcd for C19H18NO5 -[M-H]-:340.1190；Found:340.1189.
2，3-二苯基-2-(2-苯乙酰胺)-戊二酸(2c)
Figure BDA0003180314680000113
83.4mg,58％yield,白色固体,dr＝4:1；
1H NMR(400MHz,CD3OD)δ7.39–7.32(m,6H),7.30–7.23(m,6H),7.16–7.10(m,6H),6.99–6.93(m,3H),4.60(dd,J＝11.7,2.6Hz,1H),3.49(s,2H),3.11(dd,J＝16.6,2.6Hz,1H),2.80(dd,J＝16.6,11.7Hz,1H).
13C NMR(101MHz,CD3OD)δ175.75,173.95,172.69,139.82,139.59,136.26,136.08,130.94,130.61,130.53,130.49,129.97,129.81,129.59,129.44,129.23,129.03,128.99,128.87,128.70,128.59,128.42,128.36,128.32,128.25,128.20,128.02,69.54,47.91,47.76,44.85,44.34,38.12,37.83.
HRMS(m/z):Calcd for C25H22NO5 -[M-H]-:416.1503；Found:416.1501.
2-(4-氟苯甲酰胺)-2，3-二苯基戊二酸(2d)
Figure BDA0003180314680000121
76.6mg,91％yield,白色固体,dr>19:1；
1H NMR(400MHz,CD3OD)δ7.64–7.50(m,4H),7.41–7.28(m,3H),7.27–7.17(m,5H),7.16–7.07(m,2H),4.89(dd,J＝11.4,2.5Hz,1H),3.12(dd,J＝16.8,3.1Hz,1H),2.96(dd,J＝16.8,10.9Hz,1H).
13C NMR(101MHz,DMSO-d6)δ173.33,172.55,165.48,163.23,139.01,138.57,131.44(d,J＝2.6Hz),130.50(d,J＝9.0Hz),129.84,128.36,128.09,127.72,127.53(d,J＝4.8Hz),115.88,115.66,68.40,46.74,36.63.
19F NMR(376MHz,DMSO-d6)δ-108.99.
HRMS(m/z):Calcd for C24H19FNO5 -[M-H]-:420.1253；Found:420.1254.
2-(3-氟苯甲酰胺)-2，3-二苯基戊二酸(2e)
Figure BDA0003180314680000122
58.1mg,69％yield,白色固体,dr＝16:1；
1H NMR(400MHz,CD3OD)δ7.57(d,J＝7.4Hz,2H),7.46–7.26(m,5H),7.26–7.14(m,7H),4.87(dd,J＝11.5,2.6Hz,1H),3.09(dd,J＝16.7,2.9Hz,1H),2.94(dd,J＝16.7,11.6Hz,1H).
13C NMR(101MHz,CD3OD)δ175.96,167.25,165.24,162.79,140.07,139.27,138.47(d,J＝6.8Hz),131.66(d,J＝8.0Hz),130.46(s),129.15(d,J＝5.7Hz),128.94,128.71(d,J＝16.4Hz),123.66(d,J＝3.0Hz),119.54(d,J＝21.6Hz),114.96(d,J＝23.3Hz),70.23,46.32,38.24.
19F NMR(376MHz,CD3OD)δ-113.69(s).
HRMS(m/z):Calcd for C24H19FNO5 -[M-H]-:420.1253；Found:420.1257.
2-(4-甲基苯甲酰胺)-2，3-二苯基戊二酸(2f)
Figure BDA0003180314680000131
性状：67.6mg,81％yield,白色固体,dr>19:1；
1H NMR(400MHz,CD3OD)δ7.59(d,J＝7.5Hz,1H),7.43(d,J＝8.0Hz,1H),7.38–7.26(m,1H),7.26–7.17(m,3H),4.93(dd,1H),3.12(dd,J＝16.8,2.6Hz,1H),2.98(dd,J＝16.8,10.9Hz,1H),2.35(s,1H).
13C NMR(101MHz,DMSO-d6)δ173.52,172.82,166.19,141.95,139.13,138.75,132.17,129.81,129.43,128.36,128.18,127.83,127.74,127.60,127.57,68.35,46.44,36.79,21.50.
HRMS(m/z):Calcd for C25H22NO5 -[M-H]-:416.1503；Found:416.1502.
2-(3-甲基苯甲酰胺)-2,3-二苯基戊二酸(2g)
Figure BDA0003180314680000132
75mg,90％yield,白色固体,dr＝8:1；
1H NMR(400MHz,CD3OD)δ7.62–7.54(m,2H),7.39–7.17(m,10H),7.16–7.09(m,1H),7.05(dd,J＝7.5,1.1Hz,1H),4.88(dd,J＝11.7,2.7Hz,1H),3.15(dd,J＝16.7,2.7Hz,1H),2.92(dd,J＝16.6,11.6Hz,1H).
13C NMR(101MHz,DMSO-d6)δ172.87,172.23,165.97,138.60,138.21,137.70,134.54,132.00,129.31,128.28,127.80,127.69,127.65,127.31,127.06,127.05,124.31,67.86,46.05,36.26,20.89.HRMS(m/z):Calcd for C25H22NO5 -[M-H]-:416.1503；Found:416.1501.
2-(2-甲基苯甲酰胺)-2,3-二苯基戊二酸(2h)
Figure BDA0003180314680000133
72.6mg,87％yield,白色固体,dr＝6.6:1；
1H NMR(400MHz,DMSO-d6)δ13.19(s,1H),12.02(s,1H),8.32(s,1H),7.49–7.44(m,2H),7.34(dd,J＝7.2,1.9Hz,1H),7.32–7.26(m,3H),7.26–7.24(m,2H),7.23(s,1H),7.21–7.17(m,3H),7.06(dd,J＝7.0,2.3Hz,2H),4.39(dd,J＝11.7,2.1Hz,1H),3.03(dd,J＝16.6,2.5Hz,1H),2.58(dd,J＝16.6,11.9Hz,1H),2.25(s,3H).
13C NMR(101MHz,CD3OD)δ174.41,172.90,169.91,138.81,138.28,136.20,135.44,130.42,129.61,129.21,127.75,127.54,127.38,127.16,126.39,125.32,68.74,45.45,37.14,18.11.HRMS(m/z):Calcd for C25H22NO5 -[M-H]-:416.1503；Found:416.1506.
2-(噻吩-2-甲酰胺)-2,3-二苯基戊二酸(2i)
Figure BDA0003180314680000141
44.2mg,54％yield,白色固体,dr＝5:1；
1H NMR(400MHz,CD3OD)δ7.61–7.54(m,3H),7.45(dd,J＝3.7,1.0Hz,1H),7.39–7.28(m,3H),7.22(s,5H),7.06(dd,J＝5.0,3.8Hz,1H),4.84(dd,J＝10.7,3.3Hz,1H),3.08(dd,J＝16.9,3.3Hz,1H),2.96(dd,J＝16.9,10.6Hz,1H).
13C NMR(101MHz,CD3OD)δ174.54,172.71,161.43,138.58,138.46,137.75,130.34,129.05,128.30,127.73,127.65,127.48,127.40,127.36,127.18,68.77,45.43,36.67.
HRMS(m/z):Calcd for C22H18SNO5 -[M-H]-:408.0911；Found:408.0909.
2-(呋喃-2-甲酰胺)-2，3-二苯基戊二酸(2j)
Figure BDA0003180314680000142
37.3mg,55％yield,白色固体,dr＝4:1；
1H NMR(400MHz,DMSO-d6)δ13.88(s,1H),12.07(s,1H),7.83(s,1H),7.76(d,J＝1.0Hz,1H),7.47(d,J＝7.5Hz,2H),7.37–7.31(m,3H),7.30–7.27(m,1H),7.20(t,J＝6.0Hz,3H),7.15–7.11(m,2H),7.06(d,J＝3.2Hz,1H),6.59(dd,J＝3.5,1.8Hz,1H),4.75(dd,J＝11.1,2.5Hz,1H),2.90(dd,J＝16.8,2.6Hz,1H),2.78(dd,J＝16.8,11.3Hz,1H).
13C NMR(101MHz,CD3OD)δ175.74,174.12,170.35,158.84,148.90,146.33,139.94,139.42,130.27,129.21,129.08,128.89,128.62,115.41,113.09,70.01,46.24,38.34.
HRMS(m/z):Calcd for C21H17NO4 -[M-COOH]-:348.1241；Found:348.1241.
2-苯甲酰胺-2，3-二对甲苯基戊二酸(2k)
Figure BDA0003180314680000151
74mg,86％yield,白色固体,dr＝10:1；
1H NMR(400MHz,DMSO-d6)δ13.26(s,1H),12.00(s,1H),8.14(s,1H),7.68(d,J＝7.2Hz,2H),7.54–7.50(m,1H),7.45(t,J＝7.4Hz,2H),7.37(d,J＝8.2Hz,2H),7.10(d,J＝8.1Hz,2H),7.06–6.94(m,4H),4.47(dd,J＝10.8,1.9Hz,1H),2.89(dd,J＝16.6,2.5Hz,1H),2.61(dd,J＝16.6,11.5Hz,1H),2.28(s,3H),2.23(s,3H).
13C NMR(101MHz,DMSO-d6)δ173.50,172.85,166.17,136.63,136.06,135.80,135.06,131.96,129.69,128.94,128.83,128.41,128.35,127.70,110.10,68.27,46.01,36.82,21.14,21.09.HRMS(m/z):Calcd for C26H24NO5 -[M-H]-:430.1660；Found:430.1665.
2-苯甲酰胺-2，3-二(4-甲氧苯基)戊二酸(2l)
Figure BDA0003180314680000152
81mg,88％yield,白色固体,dr＝10:1；
1H NMR(400MHz,DMSO-d6)δ13.15(s,1H),12.07(s,1H),8.18(s,1H),7.70(d,J＝7.4Hz,2H),7.57–7.49(m,1H),7.45(t,J＝7.5Hz,2H),7.40(d,J＝8.8Hz,2H),7.02(d,J＝8.6Hz,2H),6.86(d,J＝8.9Hz,2H),6.78(d,J＝8.6Hz,2H),4.43(dd,J＝11.0,2.1Hz,1H),2.88(dd,J＝16.6,2.6Hz,1H),2.58(dd,J＝17.2,12.2Hz,1H).
13C NMR(101MHz,DMSO-d6)δ173.45,172.85,166.15,158.58,158.44,134.97,131.85,130.77,130.71,130.53,129.59,128.81,127.64,113.46,112.97,68.02,55.40,55.33,45.74,36.75.HRMS(m/z):Calcd for C26H24NO7 -[M-H]-:462.1558；Found:462.1559.
2-苯甲酰胺-2，3-二(4-三氟甲氧苯基)戊二酸(2m)
Figure BDA0003180314680000161
114.2mg,90％yield,白色固体,dr＝10:1；
1H NMR(400MHz,CD3OD)δ7.63–7.46(m,5H),7.43(d,J＝7.8Hz,2H),7.35(d,J＝8.8Hz,2H),7.23(d,J＝8.6Hz,2H),7.17(d,J＝8.6Hz,2H),4.79(dd,J＝10.7,3.3Hz,1H),3.07(dd,J＝16.9,3.3Hz,1H),2.87(dd,J＝16.9,10.8Hz,1H).
13C NMR(101MHz,DMSO-d6)δ172.88,172.08,167.19,147.71(d,J＝17.6Hz),137.99,137.41,134.49,132.06,131.63,130.36,128.71,128.62,128.08,127.86,121.74(d,J＝3.5Hz),120.22(d,J＝55.0Hz),119.19(d,J＝3.4Hz),67.70,46.77,35.98.
19F NMR(376MHz,DMSO-d6)δ-56.74(d,J＝20.6Hz).
HRMS(m/z):Calcd for C26H18F6NO7 -[M-H]-:470.0993；Found:470.0991.
2-苯甲酰胺-2，3-二(4-氯苯基)戊二酸(2n)
Figure BDA0003180314680000162
78.3mg,83％yield,白色固体,dr>19:1；
1H NMR(400MHz,CD3OD)δ7.65–7.59(m,2H),7.58–7.53(m,2H),7.53–7.48(m,1H),7.46–7.39(m,2H),7.38–7.32(m,2H),7.26–7.21(m,2H),7.20–7.13(m,2H),4.79(dd,J＝10.7,3.0Hz,1H),3.08(dd,J＝16.9,3.3Hz,1H),2.87(dd,J＝16.9,10.8Hz,1H).
13C NMR(101MHz,CD3OD)δ175.57(s),173.69(s),169.19(s),138.52(s),137.79(s),135.65(s),134.67(s),134.54(s),132.99(s),132.12(s),130.86(s),129.70(s),129.19(s),128.91(s),128.10(s),69.57(s),46.43(s),37.78(s).
HRMS(ESI-)m/z calcd.for C24H18Cl2NO5 -[M-H]-:470.0568；Found:470.0563.
2-苯甲酰胺-2，3-二(4-氟苯基)戊二酸(2o)
Figure BDA0003180314680000171
79mg,90％yield,白色固体,dr>19:1；
1H NMR(400MHz,CD3OD)δ7.63–7.57(m,4H),7.55–7.49(m,1H),7.45–7.39(m,2H),7.24–7.19(m,2H),7.12–7.05(m,2H),7.00–6.93(m,2H),4.85(dd,J＝10.8,3.2Hz,1H),3.07(dd,J＝16.8,3.3Hz,1H),2.88(dd,J＝16.9,10.8Hz,1H).
13C NMR(101MHz,DMSO-d6)δ173.08,172.33,166.87,161.68(d,J＝243.2Hz),161.50(d,J＝243.7Hz),134.82(d,J＝2.9Hz),134.66,134.35(d,J＝2.9Hz),131.98,131.63(d,J＝8.0Hz),130.46(d,J＝8.0Hz),128.75,128.62,127.94,127.86,114.83(d,J＝21.0Hz),114.27(d,J＝21.1Hz),67.76,46.52,36.21.
19F NMR(376MHz,DMSO-d6)δ-115.62,-115.98.
HRMS(m/z):Calcd for C24H18F2NO5 -[M-H]-:438.1159；Found:438.1158.
2-苯甲酰胺-2，3-二(4-[1,1’-联苯基])戊二酸(2p)
Figure BDA0003180314680000172
100mg,90％yield,白色固体,dr>19:1；
1H NMR(400MHz,DMSO-d6)δ13.37(s,1H),12.14(s,1H),8.52(s,1H),7.83–7.76(m,2H),7.73–7.68(m,2H),7.68–7.60(m,6H),7.59–7.53(m,3H),7.52–7.41(m,6H),7.39–7.30(m,2H),7.24(d,J＝8.3Hz,2H),4.55(dd,J＝11.6,2.7Hz,1H),3.01(dd,J＝16.7,2.7Hz,1H),2.67(dd,J＝16.8,11.6Hz,1H).
13C NMR(101MHz,DMSO-d6)δ173.41,172.65,166.64,140.14,140.10,139.31,139.20,138.29,137.89,134.93,132.09,130.58,129.49,129.23,128.95,128.02,127.96,127.15,127.06,126.41,126.02,68.30,46.45,36.63.
HRMS(m/z):Calcd for C36H28NO5 -[M-H]-:554.1973；Found:554.1974.
2-苯甲酰胺-2，3-二(3-甲氧苯基)戊二酸(2q)
Figure BDA0003180314680000181
64.8mg,70％yield,白色固体,dr＝10:1；
1H NMR(400MHz,CD3OD)δ7.62–7.45(m,3H),7.45–7.34(m,2H),7.32–7.23(m,2H),7.20–7.10(m,2H),7.00–6.69(m,4H),4.88(dd,J＝10.9,2.9Hz,1H),3.80(s,3H),3.66(s,3H),3.15(dd,J＝16.8,2.9Hz,1H),2.99(dd,J＝16.4,11.0Hz,1H).
13C NMR(101MHz,CD3OD)δ174.62,172.87,167.43,159.45,159.28,140.17,139.50,134.66,131.48,128.77,128.57,128.31,126.54,121.13,119.79,114.63,113.94,113.10,112.84,68.70,54.29,54.09,45.36,36.85.
HRMS(m/z):Calcd for C25H23NO5 -[M-COOH]-:418.1660；Found:418.1662.
2-苯甲酰胺-2，3-二(3-甲苯基)戊二酸(2r)
Figure BDA0003180314680000182
72mg,84％yield,白色固体,dr＝7.3:1；
1H NMR(400MHz,CD3OD)δ7.55–7.49(m,2H),7.47(t,J＝7.2Hz,1H),7.42–7.29(m,4H),7.27–7.20(m,1H),7.13–7.09(m,2H),7.07–6.97(m,3H),4.89(dd,J＝10.8,2.9Hz,1H),3.11(dd,J＝16.8,3.0Hz,1H),2.99(dd,J＝16.8,10.8Hz,1H),2.33(s,3H),2.20(s,3H).
13C NMR(101MHz,CD3OD)δ176.04,174.38,168.70,139.89,139.19,138.73,138.55,136.08,132.77,131.39,129.80,129.64,129.39,129.25,129.06,128.80,127.83,127.22,126.08,70.17,46.27,38.09,21.71,21.43.
HRMS(m/z):Calcd for C25H23NO3 -[M-COOH]-:386.1762；Found:386.1765.
2-苯甲酰胺-2，3-二(2-甲苯基)戊二酸(2s)
Figure BDA0003180314680000183
27mg,32％yield,白色固体,dr＝3.8:1；
1H NMR(400MHz,DMSO-d6)δ13.25(s,1H),12.03(s,1H),8.45(s,1H),7.58–7.50(m,3H),7.49–7.44(m,2H),7.44–7.38(m,1H),7.33–7.24(m,3H),7.22–7.17(m,3H),7.11–7.05(m,2H),4.43(dd,J＝11.3,2.0Hz,1H),3.34(s,6H),2.94(dd,J＝16.7,2.9Hz,1H),2.58(dd,J＝16.7,11.7Hz,1H).
13C NMR(101MHz,DMSO-d6)δ173.96,173.05,163.90,139.02,137.76,136.69,136.25,134.67,132.06,131.42,130.20,128.73,128.20,127.86,127.44,127.21,126.77,126.07,125.37,124.99,66.21,40.17,39.40,20.27,19.35.
HRMS(m/z):Calcd for C26H24NO5 -[M-H]-:430.1660；Found:430.1659.
2-苯甲酰胺-2，3-二(2-甲氧苯基)戊二酸(2t)
Figure BDA0003180314680000191
53mg,57％yield,白色固体,dr＝2.6:1；
1H NMR(400MHz,CD3OD)δ7.81(d,J＝6.9Hz,1H),7.61–7.49(m,3H),7.48–7.39(m,2H),7.34–7.25(m,2H),7.21(t,J＝7.6Hz,1H),7.04(t,J＝7.3Hz,1H),6.98(d,J＝8.2Hz,1H),6.87(d,J＝7.8Hz,2H),5.40(s,1H),3.71(s,3H),3.61(s,3H),3.10(d,J＝13.9Hz,2H).
13C NMR(101MHz,cd3od)δ174.21,172.44,166.01,158.28,157.41,140.17,137.88,135.16,131.35,128.89,128.49,128.36,126.40,121.84,119.95,119.77,119.72,112.14,110.66,71.40,54.97,54.62,44.05,36.49.
HRMS(m/z):Calcd for C25H24NO5 -[M-H]-:418.1660；Found:418.1656.
2-苯甲酰胺-2，3-二(2-萘)戊二酸(2u)
Figure BDA0003180314680000192
67.4mg,67％yield,白色固体,dr＝10:1；
1H NMR(400MHz,CD3OD)δ8.17(s,1H),7.90–7.65(m,8H),7.59–7.27(m,10H),5.20(dd,J＝10.8,2.9Hz,1H),3.28(d,J＝3.1Hz,1H),3.16(dd,J＝16.8,10.8Hz,1H).
13C NMR(101MHz,DMSO-d6)δ173.44,172.62,166.71,136.84,135.00,133.03,132.73,132.61,132.48,132.03,128.91,128.73,128.34,128.22,127.87,127.72,127.58,127.38,127.14,126.72,126.59,126.52,126.41,68.56,46.99,36.81.
HRMS(m/z):Calcd for C32H24NO5 -[M-H]-:502.1660；Found:502.1660.
2-苯甲酰胺-2，3-二(1-萘)戊二酸(2v)
Figure BDA0003180314680000201
42mg,42％yield,淡黄色固体,dr＝7.1:1；
1H NMR(400MHz,DMSO-d6)δ14.58(s,1H),12.24(s,1H),8.46(d,J＝8.6Hz,1H),8.28(d,J＝7.6Hz,1H),8.09(s,1H),8.01–7.90(m,2H),7.79(dd,J＝14.0,8.0Hz,2H),7.69(t,J＝7.8Hz,1H),7.55–7.29(m,8H),7.27–7.17(m,2H),7.09(t,J＝7.7Hz,2H),6.87(d,J＝7.4Hz,2H),6.22(d,J＝11.0Hz,1H),3.54(d,J＝16.7Hz,1H),3.07(dd,J＝16.9,11.2Hz,1H).
13C NMR(101MHz,CD3OD)δ174.86,172.36,167.03,140.60,139.91,135.05,134.71,133.77,131.13,129.56,128.33,128.14,127.92,127.53,127.41,126.41,126.37,126.09,125.67,125.20,124.63,118.37,109.99,67.59,42.03,36.28.
HRMS(m/z):Calcd for C31H23NO3 -[M-COOH]-:458.1762；Found:458.1761.
2-苯甲酰胺-3-甲基-2，3-二苯基戊二酸(2w)
Figure BDA0003180314680000202
68mg,82％yield,白色固体,dr＝10:1；
1H NMR(400MHz,CD3OD)δ7.78–7.71(m,2H),7.63–7.53(m,3H),7.51–7.44(m,2H),7.42–7.28(m,6H),7.28–7.18(m,3H),3.55(d,J＝16.4Hz,1H),2.69(d,J＝16.7Hz,1H),1.82(s,3H).
13C NMR(101MHz,DMSO-d6)δ172.87,171.54,166.74,141.66,137.47,134.81,131.96,129.43,128.86,128.71,127.75,127.64,127.30,127.11,126.78,70.79,47.29,41.12,22.08.
HRMS(m/z):Calcd for C25H22NO5 -[M-H]-:416.1503；Found:416.1504.
2-苯甲酰胺-2-苯基-3-对甲苯基戊二酸(2x)和2-苯甲酰胺-3-苯基-2-对甲苯基戊二酸(2x’)
Figure BDA0003180314680000203
71.5mg,86％yield,白色固体,rr＝1.5:1,dr＝9.7:1；
1H NMR(400MHz,CD3OD)δ7.64–7.43(m,5H),7.42–7.30(m,3H),7.26–7.19(m,3H),7.17(d,J＝8.1Hz,1H),7.12(d,J＝8.1Hz,1H),7.03(d,J＝8.0Hz,1H),4.86(dd,J＝11.0,3.1Hz,1H),3.13(dd,J＝16.8,3.0Hz,1H),2.98(dd,J＝16.8,11.7Hz,1H),2.33(s,3H).
13C NMR(101MHz,CD3OD)δ174.64,174.60,173.14,172.95,167.36,167.32,138.79,138.02,137.30,137.05,135.44,135.00,134.75,134.66,131.43,131.38,129.07,128.95,128.44,128.27,128.19,127.78,127.71,127.56,127.53,127.35,127.19,126.52,126.47,68.84,68.67,45.08,44.96,36.90,36.81,19.68,19.66.
HRMS(m/z):Calcd for C25H22NO5 -[M-H]-:416.1503；Found:416.1501.
2-苯甲酰胺-2-(4-甲氧苯基)-3苯基戊二酸(2y)和2-苯甲酰胺-3-(4-甲氧苯基)-2-苯基戊二酸(2y’)
Figure BDA0003180314680000211
76mg,88％yield,白色固体,rr＝5.9:1,dr＝10:1；
1H NMR(400MHz,CD3OD)δ7.65–7.44(m,5H),7.43–7.32(m,2H),7.31–7.12(m,5H),6.97–6.73(m,2H),4.83(dd,J＝10.9,3.0Hz,1H),3.79(s,3H),3.12(dd,J＝16.8,3.0Hz,1H),2.98(dd,J＝16.8,10.8Hz,1H).
13C NMR(101MHz,CD3OD)δ176.02,174.60,168.71,160.51,140.19,136.15,132.75,131.23,130.44,130.32,129.65,129.16,128.57,127.85,114.21,69.90,55.71,46.56,38.25.
HRMS(m/z):Calcd for C25H22NO6 -[M-H]-:432.1453；Found:432.1456.
2-苯甲酰胺-3-(4-氯苯基)-2-苯基戊二酸(2z)和2-苯甲酰胺-2-(4-氯苯基)-3-苯基戊二酸(2z’)
Figure BDA0003180314680000212
76mg,87％yield,白色固体,rr＝3.2:1,dr＝13:1；
1H NMR(400MHz,CD3OD)δ7.65–7.45(m,5H),7.44–7.27(m,5H),7.27–7.11(m,4H),4.78(dd,J＝10.4,3.5Hz,1H),3.16(dd,J＝16.8,3.0Hz,1H),2.93(dd,J＝16.8,11.2Hz,1H).
13C NMR(101MHz,CD3OD)δ175.68(s),174.23(s),168.95(s),139.12(s),138.96(s),135.87(s),134.33(s),132.90(s),132.08(s),130.92(s),129.70(s),129.11(s),129.03(s),128.91(s),127.97(s),70.08,45.99,38.13.
HRMS(m/z):Calcd for C24H19ClNO5 -[M-H]-:436.0957；Found:436.0954.
2-苯甲酰胺-2-苯基-3-(4-氟苯基)-戊二酸(2aa)和2-苯甲酰胺-2-(4-氟苯基)-3-苯基戊二酸(2aa’)
Figure BDA0003180314680000221
72mg,86％yield,白色固体,rr＝3.6:1,dr＝13.6:1；
1H NMR(400MHz,CD3OD)δ7.67–7.46(m,5H),7.44–7.34(m,2H),7.32–7.16(m,5H),7.12–7.02(m,2H),4.82(dd,J＝10.5,3.4Hz,1H),3.06(dd,J＝16.8,3.4Hz,1H),2.95(dd,J＝16.8,10.5Hz,1H).
13C NMR(101MHz,CD3OD)δ175.88,174.08,168.95,139.80,135.92,132.87,131.28(d,J＝8.2Hz),130.50,129.67,129.23,129.00,128.98,128.74,127.97,115.45(d,J＝21.7Hz),69.70,47.02,37.99.
19F NMR(376MHz,CD3OD)δ-116.62(s),-116.76(s).
HRMS(m/z):Calcd for C24H19FNO5 -[M-H]-:420.1253；Found:420.1250.
2-苯甲酰胺-2-苯基-3-(4-三氟甲基苯基)-戊二酸(2ab)
Figure BDA0003180314680000222
74mg,79％yield,白色固体,rr>19:1,dr>19:1；
1H NMR(400MHz,DMSO-d6)δ13.27(s,1H),12.08(s,1H),8.46(s,1H),7.76(d,J＝7.2Hz,2H),7.60–7.52(m,3H),7.51–7.43(m,4H),7.34–7.23(m,5H),4.56(dd,J＝11.5,2.3Hz,1H),3.04(dd,J＝16.9,2.7Hz,1H),2.64(dd,J＝16.8,11.8Hz,1H).
13C NMR(101MHz,DMSO-d6)δ173.14,172.50,166.93,144.19,138.33,134.79,132.08,130.82,128.87,128.15(d,J＝3.8Hz),128.00(d,J＝5.0Hz),127.86,127.77,124.88(dd,J＝7.2,3.8Hz),124.79(d,J＝271.8Hz),68.16,46.95,36.55.
19F NMR(376MHz,DMSO-d6)δ-60.84.
HRMS(m/z):Calcd for C25H19F3NO5 -[M-H]-:470.1221；Found:470.1224.
2-苯甲酰胺-2-苯基-3-(4-[1,1’-联苯基])戊二酸(2ac)
Figure BDA0003180314680000231
87mg,91％yield,白色固体,rr>19:1,dr>19:1；
1H NMR(400MHz,DMSO-d6)δ13.37(s,1H),12.13(s,1H),8.35(s,1H),7.78–7.71(m,2H),7.68–7.61(m,2H),7.56–7.50(m,4H),7.45(dd,J＝16.1,7.9Hz,4H),7.32(dt,J＝13.2,6.4Hz,4H),7.19(d,J＝8.3Hz,2H),4.56(dd,J＝11.2,2.0Hz,1H),2.98(dd,J＝16.7,2.7Hz,1H),2.66(dd,J＝16.6,11.7Hz,1H).
13C NMR(101MHz,DMSO-d6)δ173.35,172.64,166.48,140.03,139.14,138.66,138.38,134.97,131.95,130.45,129.39,128.86,128.36,127.87,127.81,127.57,126.96,126.26,68.40,46.31,36.69.
HRMS(m/z):Calcd for C30H24NO5 -[M-H]-:478.1660；Found:478.1658.
2-苯甲酰胺-2-(4-甲氧苯基)-3-(4-三氟甲基苯基)戊二酸(2ad)
Figure BDA0003180314680000232
81mg,81％yield,白色固体,rr>19:1,dr＝10:1；
1H NMR(400MHz,DMSO-d6)δ13.34(s,1H),12.10(s,1H),8.47(s,1H),7.73(d,J＝7.3Hz,2H),7.61–7.42(m,5H),7.30(d,J＝8.1Hz,2H),7.23(t,J＝8.0Hz,1H),7.08–7.01(m,2H),6.85(dd,J＝8.1,2.1Hz,1H),4.55(d,J＝10.6Hz,1H),3.68(s,3H),3.03(dd,J＝16.8,2.7Hz,1H),2.68(dd,J＝17.9,10.6Hz,1H).
13C NMR(101MHz,DMSO-d6)δ173.41,172.93,166.94,158.92,144.56,135.09,132.23,131.00,130.47,129.67,129.07,128.14,128.05,127.45(dd,J＝491.8,233.1Hz),125.12,113.48,68.04,55.75,47.01,36.82.
19F NMR(376MHz,DMSO-d6)δ-56.08.
HRMS(m/z):Calcd for C26H21F3NO6 -[M-H]-:500.1326；Found:500.1329.
2-苯甲酰胺-2-(4-叔丁基苯基)-3-(4-三氟甲基苯基)戊二酸(2ae)
Figure BDA0003180314680000241
74.7mg,71％yield,白色固体,rr>19:1,dr＝16.6:1；
1H NMR(400MHz,DMSO-d6)δ12.19(s,1H),8.40(s,1H),7.69(d,J＝7.4Hz,2H),7.58–7.50(m,3H),7.47–7.41(m,4H),7.37–7.30(m,4H),4.78(d,J＝11.1Hz,1H),3.02(dd,1H),2.77(dd,J＝16.7,11.8Hz,1H),1.27(s,9H).
13C NMR(101MHz,DMSO-d6)δ173.27,172.79,166.18,149.83,144.70,135.82,134.95,131.87,130.59,128.80,127.92,127.87(q,J＝31.8Hz),127.57,126.05,125.01–124.44,123.35,68.11,45.49,36.99,34.56,31.50.
19F NMR(376MHz,DMSO-d6)δ-60.89.
HRMS(m/z):Calcd for C29H27F3NO5 -[M-H]-:526.1847；Found:526.1850.
2-苯甲酰胺基-2-苯基-3-(2-萘基)-戊二酸(2af)
Figure BDA0003180314680000242
72.4mg,80％yield,白色固体,rr＝13:1,dr＝8.3:1；
1H NMR(400MHz,DMSO-d6)δ13.32(s,1H),12.07(s,1H),8.35(s,1H),7.86–7.80(m,1H),7.76–7.70(m,4H),7.61(s,1H),7.54–7.49(m,3H),7.48–7.43(m,4H),7.34–7.21(m,4H),4.68(dd,J＝11.4,2.6Hz,1H),3.04(dd,J＝16.8,2.9Hz,1H),2.79(dd,J＝16.7,11.6Hz,1H).
13C NMR(101MHz,CD3OD)δ175.98,174.38,169.00,139.36,137.51,136.01,134.52,134.28,132.78,129.68,129.63,129.11,128.97,128.83,128.81,128.58,128.48,128.31,127.92,127.07,127.00,70.31,46.80,38.18.
HRMS(m/z):Calcd for C28H22NO5 -[M-H]-:452.1503；Found:452.1506.
2-苯甲酰胺基-2-(4-甲氧苯基)-3-(2-萘基)-戊二酸(2ag)
Figure BDA0003180314680000251
86mg,89％yield,白色固体,rr＝15:1,dr＝13.8:1；
1H NMR(400MHz,CD3OD)δ7.83–7.76(m,1H),7.73–7.67(m,3H),7.55–7.50(m,4H),7.48–7.40(m,3H),7.35(t,J＝7.6Hz,3H),6.95–6.87(m,2H),5.07(dd,J＝10.6,3.4Hz,1H),3.81(s,3H),3.20(dd,J＝16.9,3.4Hz,1H),3.11(dd,J＝16.8,10.6Hz,1H).
13C NMR(101MHz,DMSO-d6)δ173.49,172.97,166.42,158.65,136.95,135.08,132.98,132.67,131.94,130.58,129.70,128.88,128.59,128.29,128.19,127.81,127.74,127.32,126.48,126.34,113.16,68.15,55.54,46.65,36.80.
HRMS(m/z):Calcd for C29H24NO6 -[M-H]-:482.1609；Found:482.1606.
2-苯甲酰胺基-2-苯基-3-(2-噻吩)-戊二酸(2ah)
Figure BDA0003180314680000252
67mg,82％yield,白色固体,rr>19:1,dr＝4.7:1；
1H NMR(400MHz,CD3OD)δ7.90–7.80(m,1H),7.69–7.57(m,3H),7.55–7.49(m,2H),7.48–7.29(m,5H),7.25–7.19(m,1H),6.90–6.85(m,2H),5.30(dd,J＝11.1,2.5Hz,1H),5.18(dd,J＝11.9,2.0Hz,0.21H),3.40(dd,J＝16.8,2.1Hz,0.21H),3.18(dd,J＝16.8,2.6Hz,1H),2.95(dd,J＝16.8,11.2Hz,1H),2.65(dd,J＝16.7,11.9Hz,0.21H).
13C NMR(101MHz,CD3OD)δ175.50,174.05,168.91,142.69,139.25,136.02,132.93,132.89,129.71,129.51,129.12,128.75,128.04,127.36,125.72,70.54,42.55,40.02.
HRMS(m/z):Calcd for C22H18SNO5 -[M-H]-:408.0911；Found:408.0915.
2-苯甲酰胺基-2-(4-氟苯基)-3-(2-噻吩)-戊二酸(2ai)
Figure BDA0003180314680000253
50.2mg,59％yield,白色固体,rr>19:1,dr＝6:1；
1H NMR(400MHz,DMSO-d6)δ13.29(s,1H),12.22(s,1H),8.48(s,1H),7.92–7.75(m,2H),7.62–7.45(m,5H),7.36(dd,J＝7.6,3.3Hz,1H),7.13(t,J＝8.9Hz,2H),6.95–6.89(m,1H),6.81(d,J＝3.2Hz,1H),4.73(dd,J＝11.3,2.0Hz,1H),3.14(dd,J＝16.5,1.7Hz,0.21H),2.98(dd,J＝16.7,2.4Hz,0.87H)
13C NMR(101MHz,DMSO-d6)δ172.49,171.70,166.00,162.36,159.94,141.50,134.42,131.50,129.89(d,J＝7.7Hz),128.36,127.38,126.83(dd,J＝211.2,153.4Hz),126.25,114.12,113.91,67.77,40.41,37.95.
19F NMR(376MHz,CD3OD)δ-116.65(s),-116.87(s).
HRMS(m/z):Calcd for C22H17FSNO5 -[M-H]-:426.0817；Found:426.0822.
2-苯甲酰胺基-2-(3-甲氧苯基)-3-(4-三氟甲基苯基)-戊二酸(2aj)
Figure BDA0003180314680000261
71mg,71％yield,白色固体,rr>19:1,dr＝7.4:1；
1H NMR(400MHz,CD3OD)δ7.62–7.55(m,2H),7.53–7.47(m,3H),7.40(t,J＝7.5Hz,4H),7.27(t,J＝8.1Hz,1H),7.19–7.10(m,2H),6.89(dd,J＝8.2,1.8Hz,1H),5.04(dd,J＝10.9,1.9Hz,1H),3.77(s,3H),3.25(dd,J＝16.9,2.8Hz,1H),2.98(dd,J＝16.9,11.1Hz,1H).
13C NMR(101MHz,CD3OD)δ175.62,174.24,169.18,160.74,145.07,140.63,135.85,132.92,131.28,130.50(dd,J＝71.3,38.8Hz),130.10,129.69,128.02,125.79(dd,J＝7.6,3.9Hz),120.96,115.12,114.26.
19F NMR(376MHz,CD3OD)δ-64.06.
HRMS(m/z):Calcd for C26H21F3NO6 -[M-H]-:500.1326；Found:500.1322.
2-苯甲酰胺基-2-(2-氯苯基)-3-(4-氯苯基)-戊二酸(2ak)
Figure BDA0003180314680000262
49mg,52％yield,白色固体,rr>19:1,dr＝2.5:1；
1H NMR(400MHz,DMSO-d6)δ14.56(s,1H),12.39(s,1H),7.90(d,J＝5.8Hz,1H),7.53–7.34(m,9H),7.31–7.24(m,2H),7.21–7.13(m,2H),5.26(d,J＝9.8Hz,1H),3.02(d,J＝16.7Hz,1H),2.85–2.71(m,1H).
13C NMR(101MHz,CD3OD)δ173.49,171.71,166.59,136.66,134.39,133.85,133.11,131.43,131.00,130.72,130.35,128.96,128.28,127.49,126.70,126.21,125.82,66.70,42.39,36.82.HRMS(m/z):Calcd for C23H18Cl2NO3 -[M-H]-:426.0669；Found:426.0666.
2-苯甲酰胺基-2-(2-甲氧基苯基)-3-(4-氯苯基)-戊二酸(2al)
Figure BDA0003180314680000271
63.5mg,68％yield,白色固体,rr>19:1,dr＝2.6:1；
1H NMR(400MHz,CD3OD)δ7.85(d,J＝7.8Hz,1H),7.51–7.30(m,7H),7.23–7.15(m,4H),7.07(td,J＝7.8,1.1Hz,1H),7.00(d,J＝8.2Hz,1H),5.26(d,J＝13.2Hz,1H),3.72(s,3H),3.23(dd,J＝16.5,0.5Hz,1H),2.90(dd,J＝16.8,12.0Hz,1H).
13C NMR(101MHz,CD3OD)δ175.42,174.45,168.02,158.79,138.62,136.20,134.21,132.76,132.23,130.50,130.39,129.74,128.81,127.75,127.55,121.09,113.36,67.02,55.92,43.97,38.10.HRMS(m/z):Calcd for C25H21ClNO6 -[M-H]-:466.1063；Found:466.1060.
以上内容是结合具体/优选的实施方式对本发明所作的进一步详细说明，不能认定本发明的具体实施只局限于这些说明。在不脱离本发明构思的前提下，其还可以对这些已描述的实施方式做出若干替代或变型，而这些替代或变型方式都应当视为属于本发明的保护范围。

Claims (10)

1.一种双芳基取代的非活化烯烃合成新型戊二酸类化合物的方法，其特征在于包括以下步骤：将反应底物、光敏剂、还原剂、碱加入反应容器中，然后在CO2氛围下加入攫氢试剂和溶剂，在可见光照射条件下室温搅拌反应0.2～48h，对反应产物进行分离纯化，制得新型戊二酸类产物，其中反应底物为双芳基取代的非活化烯烃类底物，其结构通式如下所示
Figure FDA0003180314670000011
其中R1为酰基，R2、R3各自独立的为H或烷基，Ar1、Ar2各自独立的为芳基或杂芳基。
2.根据权利要求1所述的双芳基取代的非活化烯烃合成新型戊二酸类化合物的方法，其特征在于：所述还原剂、攫氢试剂、光敏剂、反应底物和碱的摩尔比为(1～10):(0.1～1):(0.001～0.5):1:(1～5)；优选为2:0.2:0.02:1:(1～3)。
3.根据权利要求1或2所述的双芳基取代的非活化烯烃合成新型戊二酸类化合物的方法，其特征在于：所述还原剂为氢硅烷类还原剂；还原剂优选为HSiEt3、HSi(nPr)3、HSi(CH2)5Me、HSi(OMe)3、HSi(OEt)3、HSiEt2Me、HSiEtMe2、HSi(OMe)2Me、HSi(OEt)2Me、HSiCl3、Me2ClSiH、Ph2SiH2、Ph3SiH、PhSiH3、Ph2MeSiH、Ph2ClSiH、PhMe2SiH、(TMS)3SiH、iPr3SiH或PMHS；所述攫氢试剂为硫醇、硫酚、醇、硅醇、酚以及它们相应的盐或胺类；所述攫氢试剂优选为iPr3SiSH、Ph3SiSH、CH3OOCCH2SH、MeCOSH、MeCOSK、PhCOSH、CF3C6H4SH、BnSH、PhSH、CF3CH2SH、(CH2SH)2、Me2CHCHMeSH、CySH、EtOH、PrOH、Me2CHCH2OH、Ph(CH2)2OH、CF3(CH2)2SH、tBuSH、tBuOOH、Ph3SiOH、或Quinuclidin-3-ylacetate。
4.根据权利要求1～3任一项所述的双芳基取代的非活化烯烃合成新型戊二酸类化合物的方法，其特征在于：所述光敏剂为有机染料光敏剂或金属络合物光敏剂；所述光敏剂优选为4CzIPN、4CzIPN-Ph、4CzIPN-MeO、4CzIPN-Bu、4DPAIPN、3DPA2FBN、3DPAFIPN、5CzBN、DPZ、4CzPN、4CzPN-Ph、4CzPN-Bu、4CzTPN、4CzTPN-Bu、4DPAIPN、4FEIPN、DE-TMOA、TMOAQ、fac-Ir(ppy)3、fac-Ir(dF(ppy)3)、Ir(ppy)2(bpy)PF6、Ir(dFCF3ppy)2(dtbbpy)PF6或Ir(ppy)2(dtbbpy)PF6；所述碱为碳酸盐、碳酸氢盐、甲酸盐、羧酸盐、磷酸盐、烷氧基碱、氟化物、有机胺、硅氧基碱；所述碱优选为Cs2CO3、K2CO3、Na2CO3、HCOOK、HCOONa、HCOOCs、KOtBu、NaOtBu、CsOtBu、CsF、KF、NaF、DBN、DBU、iPr2EtN、Et3N、CsOAc、KOAc、NaOAc、CsOPiv、KOPiv、KOMe、NaOMe、K3PO4、Na3PO4、Cs3PO4、CF3CO2K、CF3CO2Cs、KHCO3、NaHCO3、CsHCO3或Me3SiOK。
5.根据权利要求1～4任一项所述的双芳基取代的非活化烯烃合成新型戊二酸类化合物的方法，其特征在于：所述溶剂为DMSO、DMF、CH3CN、CH2Cl2、THF、Acetone、1,4-dioxiane、MeOH、NMP或DMAc；反应体系中所述溶剂浓度为0.01-1M。
6.根据权利要求1～5任一项所述的双芳基取代的非活化烯烃合成新型戊二酸类化合物的方法，其特征在于：所述二氧化碳压力为0.1-50倍大气压；所述可见光的功率为1-100W，所述可见光的波长为350～560nm，所述可见光的光源距离为0.1～5cm。
7.根据权利要求1所述的双芳基取代的非活化烯烃合成新型戊二酸类化合物的方法，其特征在于：所述双芳基取代的非活化烯烃类底物为对称芳基取代物或不对称芳基取代物。
8.根据权利要求1所述的双芳基取代的非活化烯烃合成新型戊二酸类化合物的方法，其特征在于：所述R1为甲酰基、乙酰基、丁酰基、戊酰基、己酰基、丙酰基、苯甲酰基、苯乙酰基、苯丙酰基、苯丁酰基、苯戊酰基、苯己酰基、溴苯甲酰基、氯苯甲酰基、氟苯甲酰基、三氟甲基苯甲酰基、萘酰基、联苯酰基、甲基苯甲酰基、吡啶酰基、噻吩酰基或呋喃酰基；所述烷基为甲基、乙基、丙基、丁基、戊基、己基、庚基、辛基、壬基或癸基。
9.根据权利要求1所述的双芳基取代的非活化烯烃合成新型戊二酸类化合物的方法，其特征在于：所述芳基或杂芳基为苯基、甲苯基、乙苯基、丙苯基、丁苯基、戊苯基、己苯基、二乙基胺酰基苯基、二甲基胺酰基苯基、羧基苯基、酯基苯基、苯氧基苯基、乙氧苯基、甲氧苯基、三氟甲苯基、三氟甲氧苯基、氯苯基、氟苯基、溴苯基、联苯基、萘基、吡啶基、呋喃基或噻吩基。
10.根据权利要求1所述的双芳基取代的非活化烯烃合成新型戊二酸类化合物的方法，其特征在于所述非活化烯烃类底物包括：
Figure FDA0003180314670000031
Figure FDA0003180314670000041
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