CN108341739A - 一种α-芳基、杂芳基或烯基-α,α-二氟甲基类化合物的制备方法 - Google Patents

一种α-芳基、杂芳基或烯基-α,α-二氟甲基类化合物的制备方法 Download PDF

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CN108341739A
CN108341739A CN201710059023.3A CN201710059023A CN108341739A CN 108341739 A CN108341739 A CN 108341739A CN 201710059023 A CN201710059023 A CN 201710059023A CN 108341739 A CN108341739 A CN 108341739A
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CN108341739B (zh
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张新刚
冯璋
闵巧桥
付夏平
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Shanghai Institute of Organic Chemistry of CAS
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Abstract

本发明公开了一种α‑芳基、杂芳基或烯基‑α,α‑二氟甲基类化合物的制备方法。本发明的如式C所示的α‑芳基、杂芳基或烯基‑α,α‑二氟甲基类化合物的制备方法包含如下步骤：在溶剂中，在40℃‑140℃下，在钯盐、碱和芳基酚类化合物存在的条件下，将式A化合物或式D化合物与式B化合物进行偶联反应，即可。该制备方法具有原料简单、廉价易得、催化剂用量少、底物适用范围广、官能团兼容优秀、操作简便、反应效率高以及可以对药物和生物活性分子进行后期氟修饰等优点。本发明的制备方法制得的产物在生物医药、农药和材料科学等方面具有广泛应用。

Description

一种α-芳基、杂芳基或烯基-α,α-二氟甲基类化合物的制备 方法
技术领域
本发明涉及一种α-芳基、杂芳基或烯基-α,α-二氟甲基类化合物的制备方法。
背景技术
α-芳基或杂芳基-α,α-二氟甲基类化合物及其衍生物砌块在生物医药、农药和材料科学等方面都有着广泛的应用。然而，传统的合成α-芳基或杂芳基-α,α-二氟烷基砌块的方法中，通常是由羰基通过DAST或者Deoxofluor制得(例如，Markovsi,L.N.；Pahinnik,V.E.；Kirsanov,A.V.Synthesis 1973,787.(b)Middleton,W.J.J.Org.Chem.1975,40,574.)。但是，这些方法通常具有反应步骤冗长、官能团兼容性不好、某些反应需要用到一些剧毒的氟化剂等缺点。
最新发展的过渡金属催化的α-芳基或杂芳基-α,α-二氟甲基类化合物及其衍生物的砌块合成方法((a)Fujikawa,K.Fujioka,Y.Kobayashi,A.Amii,H.Org.Lett.2011,13,5560.(b)Fujiwara,Y.Dixon,J.A.Rodriguez,R.A.Baxter,R.D.Dixon,D.D.Collins,M.R.Blackmond,D.G.Baran,P.S.J.Am.Chem.Soc.2012,134,1494.(c)Fier,P.S.Hartwig,J.F..J.Am.Chem.Soc.2012,134,5524.(d)Prakash,G.K.S.Ganesh,S.K.Jones,J.-P.Kulkarni,A.Masood,K.Swabeck,J.K.Olah,G.A.Angew.Chem.Int.Ed.2012,51,12090.(e)Gu,Leng,Y.X.Shen,Q.Nat.Commun.2014,5,5405.(f)Matheis,C.Goossen,K.L.Org.Lett.2014,16,5984.(g)Xu,L.Vicic,D.A.J.Am.Chem.Soc.2016,138,2536.)在一定程度上解决了这类化合物合成的困难。但是，这些方法仍然存在以下两个方面的不足：1，合成所使用的二氟甲基试剂价格昂贵、合成步骤繁琐、需要通过多步复杂合成并且难以大量制备；2，合成方法官能团兼容性差、催化剂用量高、反应条件苛刻等不足。
因此，探索一种二氟甲基源廉价易得，并且合成方法高效简便、官能团兼容性好、催化剂用量低、反应条件温和的合成α-芳基、杂芳基或烯基-α,α-二氟甲基类化合物及其衍生物的方法具有显著的意义。
发明内容
本发明所要解决的技术问题在于克服现有技术中α-芳基、杂芳基或烯基-α,α-二氟甲基砌块的合成方法或具有反应步骤冗长、官能团兼容性差、涉及剧毒氟化剂等缺点；或具有合成所使用的二氟甲基试剂价格昂贵、合成步骤繁琐、需要通过多步复杂合成、难以大量制备等缺点；或具有合成方法官能团兼容性差、催化剂用量高、反应条件苛刻等不足，因而提供了一种α-芳基、杂芳基或烯基-α,α-二氟甲基类化合物的制备方法，本发明的制备方法以廉价的氟化工基础原料氯二氟甲烷为作为氟源、高效简便、合成方法官能团兼容性好、催化剂用量低、反应条件温和。
本发明的发明人通过长期而深入的研究，发现了一种以钯盐为催化剂，以芳基酚为助催化剂，经过偶联反应合成α-芳基、杂芳基或烯基-α,α-二氟甲基结构化合物及其衍生物的简便方法。该方法具有反应步骤短且原料简单易得，官能团适用范围广，可避免使用剧毒试剂等优点，因此，本发明所述的制备方法更具经济性和简洁性。在此基础上，发明人完成了本发明。
本发明是通过下述技术方案来解决上述技术问题的。
本发明提供了一种如式C所示的α-芳基、杂芳基或烯基-α,α-二氟甲基类化合物的制备方法，其包含如下步骤：在溶剂中，在40℃-140℃下，在钯盐、碱和芳基酚类化合物存在的条件下，将式A化合物或式D化合物与式B化合物进行偶联反应，即可；
本发明中，所述的偶联反应的反应温度优选为60-120℃，进一步优选80-110℃。
本发明中，所述的溶剂可为本领域进行此类反应的常规所用的溶剂；本发明优选H2O、四氢呋喃、乙醚、二甲基乙二醚(DME)、1,4-二氧六环、甲苯、N-甲基吡咯烷酮、N,N-二甲基甲酰胺、二甲基亚砜、1,3-二甲基-3,4,5,6-四氢-2-嘧啶酮、甲基叔丁基醚和N,N-二甲基乙酰胺中的一种或多种；进一步优选四氢呋喃、乙醚、二甲基乙二醚(DME)、1,4-二氧六环和甲苯中的一种或多种。
本发明中，所述的式B化合物优选以其在有机溶剂中的溶液形式参与反应，进一步优选以其二氧六环溶液参与反应。
本发明中，所述的式A化合物与所述的溶剂的摩尔体积比可为本领域此类偶联反应常规所用比例，本发明优选为0.01-1mmol/mL；进一步优选为0.2-0.5mmol/mL，更进一步优选为0.3mmol/mL。
本发明中，所述的式D化合物与所述的溶剂的摩尔体积比可为本领域此类偶联反应常规所用比例，本发明优选为0.01-1mmol/mL；进一步优选为0.2-0.5mmol/mL，更进一步优选为0.3mmol/mL。
本发明中，所述的钯盐可为本领域进行此类偶联反应常规所用的钯催化剂，包括二价钯催化剂和零价钯催化剂；其中，所述的二价钯催化剂包括Pd(OAc)2、Pd(acac)2、PdBr2、氯化烯丙基钯(II)二聚物、三氟乙酸钯、(1,5-环辛二烯)二氯化钯(II)、二(乙酰丙酮)钯(II)、[1,3-双二苯基磷丙烷]氯化钯、1,2-二(二苯基膦基)乙烷二氯化钯(II)、特戊酸钯、二氯二(三环己基瞵)钯、1,4-双(二苯基膦丁烷)二氯化钯、PdCl2(dppf)、PdCl2(PPh3)2、PdCl2(Xantphos)、[PdCl(C3H5)]2、PdCl2(MeCN)2、PdCl2(PhCN)2、 等；所述的零价钯催化剂包括Pd2(dba)3、Pd(dba)2、Pd2(dba)3.CHCl3、Pd(PPh3)4、Pd(PCy3)2、Pd(COD)2、Pd/C等。本发明优选PdQ2、PdLnCl2、Pd(PPh3)4、Pd2(dba)3.CHCl3、Pd2(dba)3或Pd(dba)2；其中，Q为醋酸根、三氟醋酸根或卤素；L选自三苯基膦、邻甲氧基三苯基膦、邻甲基三苯基膦、dppf、dppb、dppm、dppe和dppp中的一种或多种；0<n<3；进一步优选所述的钯盐为Pd2(dba)3和/或Pd(PPh3)4。
本发明中，所述的钯盐的用量可为本领域进行此类偶联反应常规所用，本发明优选所述的钯盐与所述的式A化合物或式D化合物的摩尔比为0.01-0.1；进一步优选为0.025-0.05。
本发明中，所述的碱可为本领域进行此类反应常规所用，本发明优选碱金属氢氧化物(如氢氧化锂、氢氧化钠、氢氧化钾、氢氧化铷、氢氧化铯)、碱金属碳酸盐(如碳酸锂、碳酸钠、碳酸钾、碳酸铷、碳酸铯)、碱金属碳酸氢盐(如碳酸氢锂、碳酸氢钠、碳酸氢钾、碳酸氢铷、碳酸氢铯)、碱金属磷酸盐(如磷酸锂、磷酸钠、磷酸钾、磷酸铷、磷酸铯)、碱金属有机酸盐(如碱金属甲酸盐、碱金属丙酸盐、碱金属金刚酸盐、碱金属特戊酸盐、碱金属苯甲酸盐等)、碱金属醇盐(如叔丁醇锂、叔丁醇钠、叔丁醇钾、叔丁醇镁、甲醇钠等)或有机胺(如三乙胺、二异丙基乙基胺等)中的一种或多种。进一步优选为K2CO3、KOH和Cs2CO3中的一种或多种。
本发明中，所述的碱的用量可为本领域进行此类偶联反应常规所用，本发明优选所述的碱与所述的式A化合物或式D化合物的摩尔比为1-4，进一步优选2-3。
本发明中，所述的芳基酚类化合物即为有机化学领域常规所述的芳基酚类化合物，可作为助催化剂适用于本发明所述的偶联反应中。本发明优选为各种取代或未取代的苯酚、邻苯二酚、对苯二酚中的一种或多种；其中，所述的取代为被一个或多个烷基、烷氧基或卤代烷基取代；本发明进一步优选为苯酚、对甲氧基苯酚、对三氟甲基苯酚、2,6-二甲基苯酚、2,6-二异丙基苯酚、邻苯二酚和对苯二酚中的一种或多种。
本发明中，所述的芳基酚类化合物的用量可为本领域进行此类偶联反应常规所用，本发明优选所述的芳基酚类化合物与所述的式A化合物或式D化合物的摩尔比为0.1-4；进一步优选0.25-3，更进一步优选1-2。
本发明所述的制备方法中优选还可加入配体，所述的配体可为本领域进行此类偶联反应常规所用的适用于钯催化剂的配体，如下式所述的各种膦配体：
本发明优选三苯基膦、邻甲氧基三苯基膦、邻甲基三苯基膦、dppf、dppb、dppm、dppe和dppp中的一种或多种。
本发明中，所述的配体的用量可为本领域进行此类偶联反应常规所用，本发明优选所述的配体与所述的钯盐的摩尔比为1.5-3。
本发明所述的制备方法中优选还可加入氧化剂，所述的氧化剂可为本领域进行此类偶联反应常规所用的氧化剂，本发明优选碳酸银、三氯化铁和苯醌中的一种或多种。所述的氧化剂的用量可为本领域进行此类偶联反应常规所用。
本发明中，所述的式A化合物和所述的式D化合物中，
R1、R2和R3各自独立地选自下组：氢、C1-10全氟烷基、C1-10烷基、C2-10烯基、C2-10炔基、C1-10酰胺基、C1-10羰基、氢甲酰基、卤素、取代或未取代的苯基、取代或未取代的吡啶基、取代或未取代的呋喃基、取代或未取代的噻吩基、取代或未取代的噻唑基、取代或未取代的吡咯基、C1-10烷氧基、-COOC1-10烷基、-C＝COOC1-10烷基、硝基、氰基、羟甲基、-S-C1-10烷基；或者，R1和/或R2、与R3以及相邻的双键共同构成：取代或未取代的苯基、取代或未取代的吡啶基、取代或未取代的呋喃基、取代或未取代的噻吩基、取代或未取代的噻唑基、取代或未取代的吡咯基、取代或未取代的萘基、取代或未取代的蒽基、取代或未取代的菲基、或取代或未取代的C6-20稠环芳基。
优选地，R1为氢或不存在，R2与R3以及相邻的双键共同构成取代或未取代的苯基、或取代或未取代的C6-20稠环芳基；所述的C6-20稠环芳基可以为双环稠合或多环稠合，进一步优选为C3-16环基稠合的苯基，所述的C3-16环基优选为C3-6环烷基、C3-6环杂烷基、C3-6环烯基、或C3-6杂芳基。
优选地，R1或R3各自独立地为取代或未取代的苯基。
各个Z独立地选自下组：无、F、Cl、Br、S、O或N；
本发明中，所述的式A化合物中，
当各个Z独立地为无时，R4A和R4A’各自独立地选自C1-10烷基或C3-10环烷基；或者R4A和R4A’共同构成取代的或未取代的C1-10烷基、或取代的或未取代的C3-10环烷基。
当各个Z独立地选自F、Cl或Br时，R4A和R4A’为无。
当各个Z独立地选自S、O或N时，R4A和R4A’各自独立地选自氢、C1-10烷基、C3-10环烷基、苯基、C2-10烯基、C2-10炔基、或C1-10烷氧基；或者R4A和R4A’共同构成取代的或未取代的C1-10烷基、取代的或未取代的C3-10环烷基、或取代的或未取代的苯基。
优选地，当各个Z独立地选自S或O时，R4A和R4A’为氢，或者R4A和R4A’共同构成取代的或未取代的C1-10烷基、取代的或未取代的C3-10环烷基、或取代或未取代的苯基；其中，所述的取代的或未取代的C1-10烷基优选为取代的或未取代的C2-8烷基，进一步优选为-CH2-C(CH3)2-C(CH3)2-CH2-、-CH2-C(CH3)2-CH2-或-CH2-CH2-；所述的取代的或未取代的C3-10环烷基优选为取代的或未取代的C6-8环烷基，进一步优选为所述的取代或未取代的苯基优选为
其中，所述的取代的是指基团中的一个或多个氢被选自下组的取代基所取代：C1-10全氟烷基、C1-10烷基或被一个或多个选自羟基或C1-10烷氧基的取代基所取代的C1-10烷基、C2-10烯基、C2-10炔基、C1-10酰胺基、苯并丁二酰亚胺基、C1-10羰基、氢甲酰基、卤素、未取代的苯基或被选自C1-10烷基、C2-10烯基、C2-10炔基、C1-10烷氧基中一个或多个取代基所取代的苯基、C1-10烷氧基、苄氧基、苯氧基、萘氧基、-COOC1-10烷基、-C＝CHCOOC1-10烷基、硝基、氰基、羟甲基、羟基、-S-C1-10烷基、C1-10烷基取代硅基、胺基或被一个或两个选自C1-10烷基或苯基的取代基所取代的胺基、或5元或6元的含氮杂环基
本发明中，所述的式A化合物优选选自下组：
上述各式中，Z、R4A和R4A’各自独立地如上所述；X为CH或N；Y为S、O或NR8，R8为氢、苯基、C1-10烷基、C2-10烯基、C2-10炔基、或C1-10烷氧基。
或，上述各式中一个或多个氢被选自下组的取代基所取代：C1-10全氟烷基、C1-10烷基或羟基取代的C1-10烷基、C2-10烯基、C2-10炔基、C1-10酰胺基、C1-10羰基、氢甲酰基、羟甲基、羟基、卤素、未取代的苯基或被选自C1-10烷基、C2-10烯基、C2-10炔基、C1-10烷氧基中一个或多个取代基所取代的苯基、C1-10烷氧基、苄氧基、苯氧基、萘氧基、-COOC1-10烷基、-C＝CHCOOC1-10烷基、硝基、氰基、-S-C1-10烷基、C1-10烷基取代的硅基、胺基或被一个或两个选自C1-10烷基或苯基的取代基所取代的胺基、5元或6元的含氮杂环基。
本发明中，所述的式A化合物优选选自下组：
其中，Z、R4A和R4A’各自独立地如上所述。
本发明中，所述的式A化合物优选选自下组：
本发明中，所述的式D化合物为所述的式A化合物的金属复合物，其中，M为碱金属。
本发明中，优选所述的式D化合物为所述的式A化合物与MF的复合物，其中，MF选自LiF、NaF、KF或CsF。
本发明中，所述的的式D化合物中，
当各个Z独立地为无时，R4D、R4D’和R4D”各自独立地选自：C1-10烷基、或C3-10环烷基；或者R4D、R4D’、R4D”中的两个基团共同构成取代的或未取代的C1-10烷基、或取代的或未取代的C3-10环烷基；或者R4D、R4D’、R4D”共同构成取代的或未取代的C1-10烷基、或取代的或未取代的C3-10环烷基。
当各个Z独立地选自F、Cl或Br时，R4D、R4D’和R4D”为无。
当各个Z独立地选自S、O或N时，R4D、R4D’和R4D”各自独立地选自：氢、C1-10烷基、C3-10环烷基、苯基、C2-10烯基、C2-10炔基、或C1-10烷氧基；或者R4D、R4D’和R4D”中的两个基团共同构成取代的或未取代的C1-10烷基、取代的或未取代的C3-10环烷基、或取代的或未取代的苯基；或者R4D、R4D’和R4D”共同构成取代的或未取代的C1-10烷基、或取代的或未取代的C3-10环烷基。
优选地，当各个Z独立地选自S或O时，R4D、R4D’和R4D”各自独立地选自：氢、C1-10烷基、苯基、C2-10烯基、C2-10炔基、或C1-10烷氧基；或者R4D、R4D’和R4D”中的两个基团共同构成取代的或未取代的C1-10烷基、或取代的或未取代的苯基；或者R4D、R4D’和R4D”共同构成取代的或未取代的C1-10烷基。
其中，所述的取代的是指基团中的一个或多个氢被选自下组的取代基所取代：C1-10全氟烷基、C1-10烷基或被一个或多个选自羟基或C1-10烷氧基的取代基所取代的C1-10烷基、C2-10烯基、C2-10炔基、C1-10酰胺基、苯并丁二酰亚胺基、C1-10羰基、氢甲酰基、卤素、未取代的苯基或被选自C1-10烷基、C2-10烯基、C2-10炔基、C1-10烷氧基中一个或多个取代基所取代的苯基、C1-10烷氧基、苄氧基、苯氧基、萘氧基、-COOC1-10烷基、-C＝CHCOOC1-10烷基、硝基、氰基、羟甲基、羟基、-S-C1-10烷基、C1-10烷基取代硅基、胺基或被一个或两个选自C1-10烷基或苯基的取代基所取代的胺基、5元或6元的含氮杂环基。
本发明中，所述的式D化合物优选选自下组：
上述各式中，X为CH或N；Y为S、O或NR8，R8为氢、苯基、C1-10烷基、C2-10烯基、C2-10炔基或C1-10烷氧基；
或，上述各式中一个或多个氢被选自下组的取代基所取代：C1-10全氟烷基、C1-10烷基或羟基取代的C1-10烷基、C2-10烯基、C2-10炔基、C1-10酰胺基、C1-10羰基、氢甲酰基、羟甲基、羟基、卤素、未取代的苯基或被选自C1-10烷基、C2-10烯基、C2-10炔基、C1-10烷氧基中一个或多个取代基所取代的苯基、C1-10烷氧基、苄氧基、苯氧基、萘氧基、-COOC1-10烷基、-C＝CHCOOC1-10烷基、硝基、氰基、-S-C1-10烷基、C1-10烷基取代的硅基、胺基或被一个或两个选自C1-10烷基或苯基的取代基所取代的胺基、或5元或6元的含氮杂环基；。
本发明中，所述的式D化合物优选选自下组：
本发明中，所述的式C化合物优选选自下组：
或，上述各式中一个或多个氢被选自下组的取代基所取代：C1-10全氟烷基、C1-10烷基或羟基取代的C1-10烷基、C2-10烯基、C2-10炔基、C1-10酰胺基、C1-10羰基、氢甲酰基、羟甲基、羟基、卤素、未取代的苯基或被选自C1-10烷基、C2-10烯基、C2-10炔基、C1-10烷氧基中一个或多个取代基所取代的苯基、C1-10烷氧基、苄氧基、苯氧基、萘氧基、-COOC1-10烷基、-C＝CHCOOC1-10烷基、硝基、氰基、-S-C1-10烷基、C1-10烷基取代的硅基、胺基或被一个或两个选自C1-10烷基或苯基的取代基所取代的胺基、或5元或6元的含氮杂环基。
本发明中，所述的制备方法优选还包含后处理过程，所述的后处理为将通过上述制备方法制得的产物通过本领域常规分离纯化方法进行分离纯化，具体手段包括：重结晶、薄层层析、柱层析等。所述的分离纯化方法均可采用本领域此类方法的常规条件和参数。例如，进行重结晶时，可采用极性溶剂与非极性溶剂的混合溶剂，优选为乙酸乙酯-石油醚，乙醇-石油醚等混和溶剂。使用薄层层析和柱层析时，所用的展开剂可单一的溶剂，也可采用混合溶剂，例如石油醚或乙酸乙酯-石油醚的混合溶剂等。
本发明还进一步提供了如式A、C或D所示的化合物，其结构如上述定义所述；
除非另有说明，在本发明说明书和权利要求书中出现的以下术语具有下述含义：
本文所述的“PPh3”为三苯基膦；“dba”为二亚苄基丙酮。
本发明所述的“α-芳基、杂芳基或烯基-α,α-二氟甲基类化合物”、“α-芳基、杂芳基或烯基-α,α-二氟甲基结构及其衍生物砌块化合物”可互换使用，均指如式C所示的化合物。
如本文所用，术语“C1-10烷基”指具有1-10个碳原子的直链或支链烷基、亚烷基、次烷基，例如甲基、乙基、丙基、异丙基、丁基、异丁基、仲丁基、叔丁基、戊基、己基、庚基、辛基、壬基、癸基或类似基团；可优选为C1-8烷基、C1-6烷基、或C1-4烷基。
如本文所用，术语“C1-10亚烷基”指具有1-10个碳原子的直链或支链亚烷基，例如亚甲基(-CH2-)、亚乙基(-CH2CH2-)等。
如本文所用，术语“苯基”指Ph-，也包括亚苯基(如)等。
如本文所用，术语“C3-10环烷基”指具有3-10个碳原子的直链或支链环烷基、亚环烷基、次环烷基，例如环丙基、环丁基、环戊基、环己基、环庚基、环辛基或类似基团；可优选为C3-8环烷基、C3-6环烷基、或C3-4环烷基。
术语“C2-10烯基”指具有2-10个碳原子的直链或支链的烯基，例如乙烯基、烯丙基、1-丙烯基、异丙烯基、1-丁烯基、2-丁烯基、戊烯基、己烯基、庚烯基、辛烯基、壬烯基、癸烯基、或类似基团；可优选为C2-8烯基、C2-6烯基或C2-4烯基。
术语“C2-10炔基”是指具有2-10个碳原子的直链或支链的炔基，例如乙炔基、丙炔基、丁炔基、戊炔基、己炔基、庚炔基、辛炔基、壬炔基、癸炔基、或类似基团；可优选为C2-8炔基、C2-6炔基或C2-4炔基。
术语“C1-10烷氧基”指具有1-10个碳原子的直链或支链烷氧基，例如甲氧基、乙氧基、丙氧基、异丙氧基、丁氧基、异丁氧基、仲丁氧基、叔丁氧基、或类似基团；可优选为C2-8烷氧基、C2-6烷氧基或C2-4烷氧基。
术语“C1-10酰胺基”是指具有1-10个碳原子的酰胺基(-CONH-)，例如甲酰胺基、乙酰胺基、丙酰胺基、异丙酰胺基、丁酰胺基等；可优选为C2-8酰胺基、C2-6酰胺基或C2-4酰胺基。
术语“C1-10羰基”是指具有1-10个碳原子的羰基(-CO-)，例如甲基羰基、乙基羰基、丙基羰基、异丙基羰基、丁基羰基等等；可优选为C2-8羰基、C2-6羰基或C2-4羰基。
术语“卤素”指氟、氯、溴、或碘。
术语“卤代的”指基团中的H被相同或不同的一个或多个卤素原子所取代，例如三氟甲基、五氟乙基、三氟甲氧基、二氟乙烯基或类似基团。
术语“C1-10烷基-羰基”指C1-10烷基-(C＝O)-。
术语“苯并基团”指含有苯环的两个或两个以上的环并在一起的稠环，包括苯并苯基(即萘基)、苯并萘基、苯并5元杂环、苯并5元杂环并苯基、苯并6元杂环、苯并6元杂环并苯基，或5元杂环并苯环并5元杂环或5元杂环并苯环并6元杂环的三环苯并杂环基等等。较佳地，为苯并苯基(即萘基)、苯并萘基(蒽基或菲基)、苯并5元杂环、苯并5元杂环并苯基(如)、苯并6元杂环、或苯并6元杂环并苯基。更具体地，如苯并噻吩环、苯并吡咯环、苯并呋喃环、苯并噻吩环并苯基、苯并吡咯环并苯基、苯并呋喃环并苯基等。
术语“5元杂环”是指含有选自氮、氧或硫的一个或多个杂原子的5元环，例如吡咯、呋喃、噻吩等等。
术语“6元杂环”是指含有选自氮、氧或硫的一个或多个杂原子的6元环，例如吡啶、哌啶、嘧啶、哌嗪、吗啉等等。
其中，“5元或6元的含氮杂环基”是指含有氮原子的5元或6元杂环基，例如吗啉基。
本发明各个基团中的一个或多个氢可被选自下组的取代基所取代：C1-10全氟烷基、C1-10烷基或羟基取代的C1-10烷基、C2-10烯基、C2-10炔基、C1-10酰胺基(包括苯并丁二酰亚胺基)、C1-10羰基、氢甲酰基、羟甲基、羟基、卤素、未取代的苯基或被选自C1-10烷基、C2-10烯基、C2-10炔基、C1-10烷氧基中一个或多个取代基所取代的苯基、C1-10烷氧基、苄氧基、苯氧基、萘氧基、-COOC1-10烷基、-C＝CHCOOC1-10烷基、硝基、氰基、羟基、-S-C1-10烷基、C1-10烷基取代硅基、胺基或被一个或两个选自C1-10烷基或苯基的取代基所取代的胺基、5元或6元的含氮杂环基。
在符合本领域常识的基础上，上述各优选条件，可任意组合，即得本发明各较佳实例。
本发明所用试剂和原料均市售可得。
本发明的积极进步效果在于：
1、本发明的制备方法采用廉价易得的工业原料二氟甲基试剂作为氟源；采用性质稳定、易于制备和易于储存的芳基、杂芳基、烯基硼酸或芳基、杂芳基、烯基硼酸酯作为偶联因子；采用简单易得的催化剂和助催化剂。更重要的是，本发明的制备方法的底物适用性非常广泛，包括普通芳基，含杂原子的芳基以及各种带有复杂结构的天然活性分子和药物分子等。
2、本发明的制备方法所使用的原料简单易得，且无需经过预活化处理，催化剂的用量极低，反应条件温和，操作简便，反应效率高。
3、本发明制得的α-芳基、杂芳基或烯基-α,α-二氟甲基结构及其衍生物砌块在生物医药、农药和材料科学等方面都有着广泛的应用。
具体实施方式
下面通过实施例的方式进一步说明本发明，但并不因此将本发明限制在所述的实施例范围之中。下列实施例中未注明具体条件的实验方法，按照常规方法和条件，或按照商品说明书选择。除非另外说明，否则百分比和份数按重量计算。
制备例：钯催化的芳基硼酸新戊二醇酯的通用合成方法(Ar-Bneop):
根据文献方法(Molander,G.A.Trice,S.L.J.Dreher,S.D.J.Am.Chem.Soc.2010,132,17701-17703),向氩气无水无氧保护的50mL的Schlenk反应瓶中依次加入无水KOAc(12mmol,1.18g,3.0当量),B2(OH)4(8mmol,720mg,2.0当量),Xphos(0.8-6mol％),XPhos-Pd-G1(0.4-3mol％),和相应的芳基或者杂芳基卤代物(4mmol,1.0当量)或者芳基或者杂芳基三氟甲磺酸酚酯(4mmol,1.0当量),最后加入新蒸的无水EtOH(20mL)。反应混合物加热至80度搅拌反应4小时。然后将其冷却至室温,减压浓缩,所得固体加入100mL乙酸乙酯稀释后用适量饱和食盐水洗涤。有机相无水硫酸镁干燥后过滤浓缩。浓缩所得固体溶于20mL二氯甲烷并加入新戊二醇(8mmol,833mg,2.0eq.)。所得溶液于室温下搅拌反应8小时，反应结束后浓缩柱层析即得目标产物。
实施例1：化合物26a
使用Xphos(19mg,0.04mmol,1mol％),XPhos-Pd-G1(15.8mg,0.02mmol,0.5mol％)和芳基氯26b(1.17g,4.0mol,1.0当量)合成得到芳基新戊二醇酯26a(1.12g,产率75％)。芳基新戊二醇酯26a通过硅胶柱柱层析纯化(洗脱剂为二氯甲烷)得到，为白色固体，熔点为74-76℃。1H NMR(400MHz,CDCl3)δ7.74(d,J＝8.0Hz,2H),7.46(d,J＝8.0Hz,2H),3.77(s,4H),1.14(s,18H),1.14-1.07(m,3H),1.02(s,6H).13C NMR(100MHz,CDCl3)δ133.5,131.1,125.6,107.4,91.5,72.3,31.9,21.9,18.7,11.3(硼取代的碳原子没有观测到).IR(薄膜法)vmax3075,2942,2890,2865,2155,1603cm-1.MS(EI):m/z(％)370(M+),369(M+),328,327(100),257.HRMS:理论计算值C22H35O2Si10B(M+):369.2536；实测值:369.2528.
实施例2:化合物34a
使用Xphos(38.1mg,0.08mmol,2mol％),XPhos-Pd-G1(31.5mg,0.04mmol,1mol％)和芳基溴34b(1.60g,4.0mol,1.0当量)合成得到芳基新戊二醇酯34a(1.42g,产率82％)。芳基新戊二醇酯34a通过硅胶柱柱层析纯化(洗脱剂为CH2Cl2/EtOAc＝20:1)得到，产物为白色固体，其熔点为176-178℃。1H NMR(400MHz,CDCl3)δ8.37(s,1H),8.32(dd,J＝8.4Hz,3.2Hz,2H),7.94(dd,J＝8.4Hz,3.2Hz,2H),7.69(d,J＝8.1Hz,2H),7.47(t,J＝7.6Hz,1H),7.35(t,J＝7.6Hz,1H),7.06(d,J＝8.0Hz,2H),3.82(s,4H),2.23(s,3H),1.05(s,6H)。13C NMR(100MHz,CDCl3)δ144.8,140.2,138.4,134.9,133.0,129.6,127.1,126.5,126.4,125.8,123.9,120.0,115.0,114.2,72.4,31.9,21.9,21.4(硼取代的碳原子没有观测到)。IR(薄膜法)vmax3042,2959,2886,1618,1598cm-1。MS(DART):m/z(％)451[(M+NH4)+](100),450[(M+NH4)+]。HRMS:理论值C24H28O4N2 10BS[(M+NH4)+]:450.1894；实测值:450.1889.
实施例3:化合物35a
使用xphos(38.1mg,0.08mmol,2mol％),XPhos-Pd-G1(31.5mg,0.04mmol,1mol％),和芳基氯35b(1.34g,4.0mol,1.0当量)合成得到芳基新戊二醇酯35a(1.29g,产率：78％)。芳基新戊二醇酯35a通过硅胶柱柱层析纯化(CH2Cl2/EtOAc＝25:1)得到，为白色固体，熔点为144-146℃。1H NMR(500MHz,CDCl3)δ7.96(s,1H),7.57(dd,J＝7.8Hz,0.9Hz,1H),7.51(d,J＝8.1Hz,1H),7.33(d,J＝7.8Hz,2H),7.25(td,J＝7.8Hz,1.4Hz,1H),7.13(td,J＝7.8Hz,1.4Hz,1H),3.76(s,4H),1.49(s,9H),1.01(s,6H).13C NMR(125MHz,CDCl3)δ152.4,138.7,137.9,134.8,132.4,131.9,131.2,127.3,127.1,126.6,126.5,125.9,81.8,72.3,31.9,28.1,21.8(硼取代的碳原子没有观测到)。IR(薄膜法)vmax 3059,3003,2965,1715,1598,1475cm-1.MS(DART):m/z(％)429[(M+NH4)+](100),428[(M+NH4)+],411(M+).HRMS:理论值C22H30O4N2 10BS[(M+NH4)+]:428.2050；实测值:428.2049.
实施例4:化合物39a
使用Xphos(38.1mg,0.08mmol,2mol％),XPhos-Pd-G1(31.5mg,0.04mmol,1mol％)和芳基溴39b(1.10g,4.0mol,1.0当量)合成得到芳基新戊二醇酯39a(900mg,产率：73％)。芳基新戊二醇酯35a通过硅胶柱柱层析纯化(CH2Cl2)得到，为白色固体，熔点为187-189℃。1H NMR(400MHz,CDCl3)δ8.24(d,J＝8.2Hz,2H),7.96(d,J＝8.2Hz,2H),7.79-7.77(m,1H),7.58-7.56(m,1H),7.35-7.33(m,2H),3.78(s,4H),1.03(s,6H).13C NMR(100MHz,CDCl3)δ163.1,150.7,142.1,134.2,128.7,126.5,125.1,124.5,120.0,110.5,72.3,31.8,21.8(硼取代的碳原子没有观测到)。IR(薄膜法)vmax 3064,2959,2936,2900,1605,1570cm-1.MS(EI):m/z(％)308(M+),307(M+)(100),221。HRMS:理论值C18H18NO3 10B(M+):306.1416；实测值:306.1414。
实施例5:化合物40a
使用Xphos(114.2mg,0.24mmol,6mol％),XPhos-Pd-G1(94.4mg,0.12mmol,3mol％)和杂芳基溴40b(948mg,4.0mol,1.0当量)合成得到芳基新戊二醇酯40a(702mg,产率：65％)。芳基新戊二醇酯35a通过硅胶柱柱层析纯化(CH2Cl2/EtOAc/Et3N＝500:25:1)得到，为黄色油状物。1H NMR(400MHz,CDCl3)δ7.76(s,1H),7.60(s,1H),7.34-7.28(m,3H),7.22-7.20(m,2H),5.30(s,2H),3.69(s,4H),0.99(s,6H)。13C NMR(125MHz,CDCl3)δ145.2,136.3,135.4,128.7,128.0,127.8,72.0,55.7,31.9,21.9(硼取代的碳原子没有观测到)。IR(薄膜法)vmax 3099,2960,2942,2897,1603,1550cm-1。MS(EI):m/z(％)270(M+),269(M+)(100),183。HRS:理论值for C15H18N2O2 10B[(M-H)+]:268.1498；实测值:268.1502。
实施例6:化合物45a
室温无水无氧下，向50mL的Schlenk瓶中加入S1-2(2.60g,10mmol),SI-1(3.03g,12mmol)和pyridine(20mL)。搅拌反应24小时后,反应液用150mL乙酸乙酯稀释,适量饱和食盐水洗涤,有机相无水硫酸镁干燥浓缩后纯化得到芳基新戊二醇酯45a(3.0g,产率：63％)。芳基新戊二醇酯45a通过硅胶柱柱层析纯化(CH2Cl2/EtOAc＝20:1)得到，为白色固体，熔点为104-106℃。1H NMR(400MHz,CDCl3)δ7.96(d,J＝8.1Hz,2H),7.85(d,J＝8.1Hz,2H),5.94(d,J＝3.6Hz,1H),5.48(d,J＝2.8Hz,1H),4.62(d,J＝3.6Hz,1H),4.36-4.32(m,2H),4.12-4.04(m,2H),3.76(s,4H),1.53(s,3H),1.39(s,3H),1.30(s,3H),1.24(s,3H),1.01(s,6H)。13C NMR(100MHz,CDCl3)δ165.3,133.8,131.0,128.5,112.2,109.3,105.1,83.3,79.9,76.6,72.5,72.3,67.2,31.8,26.7,26.6,26.1,25.1,21.8(硼取代的碳原子没有观测到)。IR(薄膜法)vmax 2981,2960,2935,2899,1733,1507cm-1.MS(DART):m/z(％)477(M+),476(M+),419(100),379.HRMS:理论值for C24H34O9 10B[(M+H)+]:476.2327；实测值:476.2329。
实施例7:化合物47a
室温无水无氧下，向50mL的Schlenk瓶中加入S1-3(2.21g,9mmol),SI-1(1.51g,6mmol),pyridine(1mL,12mmol),DMAP(73mg,0.6mmol)和CH2Cl2(30mL)。搅拌反应24小时后,反应液用150mL乙酸乙酯稀释,适量饱和食盐水洗涤,有机相无水硫酸镁干燥浓缩后纯化得到芳基新戊二醇酯47a(2.22g,产率：80％)。芳基新戊二醇酯45a通过硅胶柱柱层析纯化(CH2Cl2/EtOAc＝20:1)得到，为无色透明油状物。1H NMR(400MHz,DMSO-d6,80℃):δ7.92(d,J＝8.0Hz,2H),7.82(d,J＝8.0Hz,2H),5.46(s,1H),4.42(t,J＝7.7Hz,1H),3.79(s,4H),3.76-3.68(m,4H),3.62(d,J＝12.2Hz,1H),2.62-2.50(m,1H),2.39-2.24(m,1H),1.39(s,9H),0.99(s,6H)。13C NMR(100MHz,DMSO-d6,80℃):δ172.0,165.1,152.9,133.3,131.0,127.8,79.3,72.5,71.4,67.6,57.0,51.5,35.2,31.1,27.6,21.0(硼取代的碳原子没有观测到)。IR(薄膜法)vmax3489,2964,2886,1751,1705,1478cm-1。MS(DART):m/z(％)462(M+)(100),461(M+)。HRMS:理论值C23H33O8N10B[(M+H)+]:461.2323；实测值:461.2326。
实施例8:化合物48a
使用KOAc(15mmol,1.47g,3.0当量),B2(OH)4(10mmol,900mg,2.0当量),Xphos(19mg,0.04mmol,0.8mol％),XPhos-Pd-G1(15.8mg,0.02mmol,0.4mol％)和杂芳基氯48b(1.81g,5.0mol,1.0当量)合成得到芳基新戊二醇酯48a(1.87g,产率：85％)。芳基新戊二醇酯48a通过硅胶柱柱层析纯化(CH2Cl2/EtOAc＝40:1)得到，为白色固体，熔点为122-124℃。1H NMR(400MHz,CDCl3)δ7.87(d,J＝7.6Hz,2H),7.74(d,J＝8.4Hz,2H),7.68(d,J＝7.6Hz,2H),6.83(d,J＝8.4Hz,2H),5.05(m,1H),3.75(s,4H),1.63(s,6H),1.17(d,J＝6.2Hz,6H),1.00(s,6H)。13C NMR(100MHz,CDCl3)δ195.7,173.0,159.4,139.7,133.5,132.0,130.6,128.5,117.0,79.2,72.3,69.2,31.8,25.3,21.8,21.4(硼取代的碳原子没有观测到)。IR(薄膜法)vmax3020,2979,2953,2930,2887,1729,1644,1599cm-1。MS(DART):m/z(％)439(M+)(100),438(M+)。HRMS:理论值C25H32O6 10B[(M+H)+]:438.2323；实测值:438.2320。
实施例9:化合物49a
使用KOAc(5.89g,60mmol,2.4当量),B2(OH)4(3.60g,40mmol,1.6当量),Xphos(95.2mg,0.2mmol,0.8mol％),XPhos-Pd-G1(78.7mg,0.1mmol,0.4mol％),Clofibrate 49b(6.08g,25.0mol,1.0当量)合成得到芳基新戊二醇酯49a(7.51g,产率：94％)。芳基新戊二醇酯49a通过硅胶柱柱层析纯化(CH2Cl2)得到，为白色固体，熔点为38-40℃。1H NMR(400MHz,CDCl3)δ7.67(d,J＝8.6Hz,2H),6.79(d,J＝8.6Hz,2H),4.21(q,J＝7.1Hz,2H),3.73(s,4H),1.60(s,6H),1.21(t,J＝7.1Hz,3H),1.00(s,6H)。13C NMR(100MHz,CDCl3)δ174.2,157.7,135.0,117.4,78.7,72.1,61.3,31.8,25.3,21.8,13.9(硼取代的碳原子没有观测到)。IR(薄膜法)vmax2963,1729,1601,1569cm-1。MS(EI):m/z(％)320(M+),319(M+),247,206,135,94(100)。HRMS:理论值C17H25O5 10B(M+):319.1831；实测值:319.1825。
实施例10:化合物50a
使用KOAc(15mmol,1.47g,3.0当量),B2(OH)4(10mmol,900mg,2.0当量),Xphos(19mg,0.04mmol,0.8mol％),XPhos-Pd-G1(15.8mg,0.02mmol,0.4mol％),heteroarylbromide 50b(2.1g,5.0mol,1.0当量)合成得到芳基新戊二醇酯50a(2.05g,产率：90％)。芳基新戊二醇酯50a通过硅胶柱柱层析纯化(CH2Cl2/EtOAc＝20:1)得到，为黄色油状物。1HNMR(400MHz,DMSO-d6,80℃):δ7.54(d,J＝8.3Hz,2H),7.39(d,J＝7.2Hz,2H),7.34(t,J＝7.5Hz,2H),7.25(t,J＝7.1Hz,1H),6.85(d,J＝8.4Hz,2H),5.33(dd,J＝7.5,4.9Hz,1H),3.70(s,4H),3.32(t,J＝7.2Hz,2H),2.76(s,3H),2.21–1.95(m,2H),1.35(s,9H),0.94(s,6H)。13C NMR(101MHz,DMSO-d6,80℃):δ159.57,154.47,141.00,134.71,128.06,127.10,125.61,114.76,78.05,76.64,71.19,44.79,35.68,33.61,31.06,27.74,20.99(硼取代的碳原子没有观测到)。IR(薄膜法)vmax3372,2964,2358,1709,1602,1509cm-1.MS(DART):m/z(％)454(M+)(100),453(M+),439,438。HRMS:理论值C26H37O5N10B[(M+H)+]:453.2796；实测值:453.2793。
实施例11:化合物51a
使用KOAc(2.94g,30mmol,3.0当量),B2(OH)4(1.80g,20mmol,2.0当量),Xphos(38mg,0.08mmol,0.8mol％),XPhos-Pd-G1(31.5mg,0.04mmol,0.4mol％)Loratadine 51b(3.83g,10.0mol,1.0当量)合成得到芳基新戊二醇酯51a(4.06g,产率：88％)。芳基新戊二醇酯51a通过硅胶柱柱层析纯化(CH2Cl2/EtOAc＝4:1)得到，为无色透明油状物。1H NMR(400MHz,CDCl3)δ8.38(dd,J＝4.8,1.2Hz,1H),7.61(s,1H),7.60(d,J＝7.6Hz,1H),7.41(d,J＝7.6Hz,1H),7.19(d,J＝7.6Hz,1H),7.06(dd,J＝7.6,4.8Hz,1H),4.12(q,J＝7.1Hz,2H),3.80(m,2H),3.74(s,4H),3.46-3.30(m,2H),3.15-3.07(m,2H),2.88-2.81(m,2H),2.52-2.45(m,1H),2.36-2.29(m,3H),1.24(t,J＝7.1Hz,3H),0.99(s,6H)。13C NMR(100MHz,CDCl3)δ156.6,155.0,145.8,141.2,137.2,136.27,136.24,134.9,134.2,133.4,131.2,128.0,121.7,77.6,71.8,60.8,44.4,31.38,31.33,31.2,30.3,30.1,21.3,14.3(硼取代的碳原子没有观测到)。IR(薄膜法)vmax3370,2961,2930,1694,1605cm-1。MS(DART):m/z(％)461(M+)(100),460(M+),406,405。HRMS:理论值C27H34O4N2 10B[(M+H)+]:460.2642；实测值:460.2638.
实施例12:化合物53a
使用KOAc(486mg,4.95mmol,3.0当量),B2(OH)4(300mg,3.3mmol,2.0当量),Xphos(47mg,0.099mmol,6mol％),XPhos-Pd-G1(39mg,0.0495mmol,3mol％)和杂芳基碘53b(0.72g,1.65mol,1.0当量)合成得到芳基新戊二醇酯53a(450mg,产率：65％)。芳基新戊二醇酯53a通过硅胶柱柱层析纯化(CH2Cl2/EtOAc＝15:1)得到，为白色固体，熔点为118-120℃。1H NMR(500MHz,CDCl3)δ7.87(d,J＝8.3Hz,2H),7.73(d,J＝8.3Hz,2H),6.60(s,1H),3.90(s,3H),3.82(s,3H),3.74(s,4H),3.44(s,3H),0.99(s,6H)。13C NMR(100MHz,CDCl3)δ172.5,164.2,161.2,140.0,134.4,125.9,89.7,72.3,54.6,54.0,34.4,31.8,21.7(硼取代的碳原子没有观测到)。MS(DART):m/z(％)423(M+),422(M+)(100),421(M+)。HRMS:理论值C18H25O6N3 10BS[(M+H)+]:421.1588；实测值:421.1586。
通用方法A:钯催化氯二氟乙烷以及芳基硼酸或芳基硼酸乙二醇酯的二氟甲基化。
向氩气无水无氧保护的25mL的Schlenk反瓶中依次加入无水K2CO3(粉末,4.0当量),对苯二酚(2.0当量),Pd2(dba)3(2.5mol％),Xantphos(7.5mol％)和ArB(OH)2(0.3or0.5mmol)或者Ar-Beg(0.3或0.5mmol级反应)。然后加入ClCF2H的1，4二氧六环溶液(2.0M,1.5mL,0.3mmol级反应或者2.5mL,0.5mmol级反应,10当量)和新蒸的1,4二氧六环(1.0mL,0.3mmol级反应或2.5mL,0.5mmol级反应)。塞上封管塞后将反应混合物加热至110度搅拌反应48小时。反应结束后浓缩柱层析即得目标产物。
通用方法B:钯催化氯二氟乙烷以及芳基硼酸新戊二醇酯·氢氧化钾盐的二氟甲基化。
零度下，向氩气无水无氧保护的25mL的Schlenk瓶中依次加入KOH(1.0当量)和Ar-Bneop(0.3or 0.5mmol),然后加入新蒸无MeOH(2mL)和新蒸的1，4二氧六环(2.0mL)。零度下搅拌30分钟后，加压浓缩除去挥发性液体。然后向反瓶中依次加入无水K2CO3(粉末,4.0当量),对苯二酚(2.0当量),Pd2(dba)3(2.5mol％),Xantphos(7.5mol％)。随后加入ClCF2H的1，4二氧六环溶液(2.0M，1.5mL，0.3mmol级反应或者2.5mL，0.5mmol级反应,10当量)和新蒸的1，4二氧六环(1.0mL，0.3mmol级反应或2.5mL，0.5mmol级反应)。塞上封管塞后将反应混合物加热至110度搅拌反应48小时。反应结束后浓缩柱层析即得目标产物。
实施例13:化合物3
根据通用方法A或者B得到目标产物3(ArB(OH)2:93mg,产率：91％,ArBeg:97mg,产率：95％,ArBneop·KOH:92mg,产率：90％)。产物通过硅胶柱柱层析纯化(正己烷)，为白色固体，其熔点为78-82℃。1H NMR(400MHz,CDCl3)δ7.70-7.68(m,2H),7.63-7.59(m,4H),7.51-7.47(m,2H),7.43-7.39(m,1H),6.72(t,J＝56.5Hz,1H)。19FNMR(376MHz,CDCl3)δ-110.4(d,J＝56.5Hz,2F)。13C NMR(100MHz,CDCl3)δ143.7(t,J＝2.0Hz),140.1,133.2(t,J＝22.4Hz),128.9,127.9,127.4,127.2,126.0(t,J＝6.0Hz),114.7(t,J＝238.5Hz)。MS(EI):m/z(％)204(M+)(100),183,152,127.HRMS:理论值:C13H10F2(M+):204.0751；实测值:204.0754.
实施例14:化合物4
根据通用方法A，用0.3mmol芳基硼酸投入反应得到4(44mg,产率：72％)。产物通过硅胶柱柱层析纯化(正己烷)，为无色透明油状物。1H NMR(400MHz,CDCl3)δ7.75(s,1H),7.73-7.71(m,1H),7.63-7.61(m,2H),7.54(t,J＝7.2Hz,1H),752-7.46(m,3H),7.39(t,J＝7.2Hz,1H),6.72(t,J＝56.4Hz,1H)。19FNMR(376MHz,CDCl3)δ-110.6(d,J＝56.4Hz,2F)。13CNMR(100MHz,CDCl3)δ141.9,140.2,134.9(t,J＝22.0Hz),129.5(t,J＝1.9Hz),129.2,128.9,127.8,127.2,124.4(t,J＝5.9Hz),124.3(t,J＝5.9Hz),114.8(t,J＝237.6Hz)。MS(EI):m/z(％)204(M+)(100),183,152,84。HRMS:理论值:C13H10F2(M+):204.0751；实测值:204.0745.
实施例15:化合物5
根据通用方法A，用0.3mmol芳基硼酸投入反应得到5(31mg,产率：50％)。产物通过硅胶柱柱层析纯化(正己烷)，为无色透明油状物。1H NMR(400MHz,CDCl3)δ7.80(d,J＝8.0Hz,1H),7.55-7.50(m,2H),7.46-7.40(m,3H),7.37-7.36(m,3H),6.55(t,J＝54.9Hz,1H)。19FNMR(376MHz,CDCl3)δ-107.4(d,J＝54.9Hz,2F)。13C NMR(100MHz,CDCl3)δ141.4(t,J＝6.6Hz),138.6,131.7(t,J＝22.2Hz),130.4(t,J＝1.8Hz),130.2,129.4,128.4,127.9,127.8,125.6(t,J＝5.2Hz),113.1(t,J＝234.6Hz)。MS(EI):m/z(％)204(M+)(100),183,154,127.HRMS:理论值:C13H10F2(M+):204.0751；实测值:204.0757.
实施例16:化合物6
根据通用方法A，用0.3mmol芳基硼酸投入反应得到6(24mg,产率：51％,19F NMR产率：78％)。产物通过硅胶柱柱层析纯化(正己烷)，为无色透明油状物。1H NMR(400MHz,CDCl3)δ7.31(s,1H),7.17(d,J＝7.7Hz,1H),7.11(d,J＝7.7Hz,1H),6.73(t,J＝55.6Hz,1H),2.39(s,3H),2.35(s,3H)。19FNMR(376MHz,CDCl3)δ-112.9(d,J＝55.6Hz,2F)。13C NMR(100MHz,CDCl3)δ135.6,133.0(t,J＝4.5Hz),132.0(t,J＝20.5Hz),131.2(t,J＝1.7Hz),131.0,126.3(t,J＝7.3Hz),114.5(t,J＝237.7Hz),20.9,18.0。MS(EI):m/z(％)156(M+),141,105(100).HRMS:理论值:C9H10F2(M+):156.0751；实测值:156.0747.
实施例17:化合物7
根据通用方法A，用0.3mmol芳基硼酸投入反应得到7(64mg,产率：91％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝40:1)，为白色固体，其熔点为78-80℃。1H NMR(400MHz,CDCl3)δ7.45-7.43(m,4H),7.42-7.38(m,2H),7.36-7.32(m,1H),7.03(d,J＝8.5Hz,2H),6.60(t,J＝56.7Hz,1H),5.10(s,2H)。19FNMR(376MHz,CDCl3)δ-108.4(d,J＝56.7Hz,2F)。13C NMR(100MHz,CDCl3)δ160.5(t,J＝1.4Hz),136.4,128.6,128.1,127.4,127.1(t,J＝5.9Hz),127.0,114.9,114.8(t,J＝236.0Hz),70.1。MS(EI):m/z(％)234(M+),141,131,91(100).HRMS:理论值:C14H12OF2(M+):234.0856；实测值:234.0858.
实施例18:化合物8
根据通用方法A，用0.3mmol芳基硼酸投入反应得到8(55mg,产率：83％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝40:1)，为无色透明油状物。1H NMR(400MHz,CDCl3)δ7.47(d,J＝8.4Hz,2H),7.38(t,J＝7.9Hz,2H),7.17(t,J＝7.4Hz,1H),7.05(d,J＝8.2Hz,4H),6.63(t,J＝56.6Hz,1H)。19FNMR(376MHz,CDCl3)δ-109.0(d,J＝56.6Hz,2F)。13C NMR(100MHz,CDCl3)δ159.6(t,J＝2.0Hz),156.2,129.9,128.9(t,J＝22.6Hz),127.3(t,J＝6.0Hz),124.1,119.6,118.3,114.6(t,J＝236.8Hz)。MS(EI):m/z(％)220(M+)(100),169,141,77。HRMS:理论值:C13H10OF2(M+):220.0700；实测值:220.0706。
实施例19:化合物9
根据通用方法A，用0.3mmol芳基硼酸投入反应得到9(47mg,产率：82％)。产物通过硅胶柱柱层析纯化(正己烷)，为无色透明油状物。1H NMR(400MHz,CDCl3)δ7.07-7.02(m,2H),6.89(d,J＝8.2Hz,1H),6.56(t,J＝56.7Hz,1H),3.91(s,3H),3.90(s,3H)。19FNMR(376MHz,CDCl3)δ-108.2(d,J＝56.7Hz,2F)。13C NMR(100MHz,CDCl3)δ150.9(t,J＝2.0Hz),149.2,126.9(t,J＝22.7Hz),118.7(t,J＝7.0Hz),114.9(t,J＝237.7Hz),110.7,108.0(t,J＝5.3Hz),55.91,55.90。MS(EI):m/z(％)188(M+)(100),173,169,145,130,125。HRMS:理论值:C9H10O2F2(M+):188.0649；实测值:188.0645。
实施例20:化合物10
根据通用方法A，用0.3mmol芳基硼酸投入反应得到10(34mg,产率：65％；19F NMR产率：82％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝30:1)，为无色透明油状物。1HNMR(400MHz,CDCl3)δ6.99-6.97(m,2H),6.85(d,J＝7.8Hz,1H),6.54(t,J＝56.6Hz,1H),6.01(s,2H).19FNMR(282MHz,CDCl3)δ-108.0(d,J＝56.6Hz,2F)。13C NMR(100MHz,CDCl3)δ149.5(t,J＝1.4Hz),148.0,128.3(t,J＝22.6Hz),120.1(t,J＝7.1Hz),114.6(t,J＝238.1Hz),108.2,105.8(t,J＝5.4Hz),101.5。MS(EI):m/z(％)172(M+),171(100),153,91,63。HRMS:理论值:C8H6O2F2(M+):172.0336；实测值:172.0338。
实施例21:化合物11
根据通用方法A，用0.3mmol芳基硼酸投入反应得到11(72mg,产率：84％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝40:1)，为白色固体，其熔点为76-80℃。1H NMR(400MHz,CDCl3)δ8.40-8.38(m,1H),7.87-7.85(m,1H),7.64(d,J＝8.1Hz,2H),7.58(d,J＝8.2Hz,2H),7.56-7.53(m,2H),7.50(d,J＝8.3Hz,1H),7.40(t,J＝7.9Hz,1H),6.88(d,J＝7.6Hz,1H),6.70(t,J＝56.5Hz,1H),5.30(s,2H)。19FNMR(376MHz,CDCl3)δ-110.4(d,J＝56.5Hz,2F)。13C NMR(100MHz,CDCl3)δ154.2,140.0(t,J＝2.0Hz),134.6,133.9(t,J＝22.4Hz),127.5,127.4,126.5,125.8(t,J＝6.0Hz),125.7(t,J＝8.2Hz),125.3,122.0,120.7,114.6(t,J＝238.6Hz),105.2,69.4。MS(EI):m/z(％)284(M+),234,165,141(100),115,91。HRMS:理论值:C18H14OF2(M+):284.1013；实测值:284.1015。
实施例22:化合物12
根据通用方法A，用0.3mmol芳基硼酸投入反应得到12(48mg,产率：74％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝3:1)，为无色透明油状物。1H NMR(400MHz,CDCl3)δ7.41(d,J＝8.3Hz,2H),6.93(d,J＝8.5Hz,2H),6.58(t,J＝56.9Hz,1H),3.87(t,J＝4.8Hz,4H),3.22(t,J＝4.8Hz,4H)。19FNMR(376MHz,CDCl3)δ-108.2(d,J＝56.9Hz,2F)。13CNMR(100MHz,CDCl3)δ152.8(t,J＝1.5Hz),126.7(t,J＝5.9Hz),125.2(t,J＝22.8Hz),115.1(t,J＝236.8Hz),114.8,66.7,48.5。MS(EI):m/z(％)213(M+),194,155(100),154,127。HRMS:理论值:C11H13NOF2(M+):213.0965；实测值:213.0959。
实施例23:化合物13
根据通用方法A，用0.3mmol芳基硼酸投入反应得到13(35mg,产率：62％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝30:1)，为无色透明油状物。1H NMR(400MHz,CDCl3)δ7.41(d,J＝8.2Hz,2H),7.35(d,J＝8.3Hz,2H),6.61(t,J＝56.6Hz,1H),2.99(q,J＝7.4Hz,2H),1.35(t,J＝7.4Hz,3H)。19FNMR(376MHz,CDCl3)δ-110.2(d,J＝56.5Hz,2F)。13CNMR(100MHz,CDCl3)δ140.7(t,J＝2.1Hz),131.4(t,J＝22.4Hz),127.9,126.0(t,J＝6.0Hz),114.6(t,J＝238.3Hz),26.9,14.1。MS(EI):m/z(％)188(M+)(100),173,160,153,127.HRMS:理论值:C9H10SF2(M+):188.0471；实测值:188.0477.
实施例24:化合物14
根据通用方法A，用0.3mmol芳基硼酸投入反应得到14(50mg,产率：82％)。产物通过硅胶柱柱层析纯化(正己烷)，为无色透明油状物。1H NMR(400MHz,CDCl3)δ7.61(d,J＝7.8Hz,2H),7.48(d,J＝7.8Hz,2H),6.62(t,J＝56.6Hz,1H),0.29(s,9H)。19FNMR(376MHz,CDCl3)δ-110.9(d,J＝56.6Hz,2F)。13C NMR(100MHz,CDCl3)δ144.0,134.6(t,J＝22.5Hz),133.6,124.7(t,J＝5.9Hz),114.8(t,J＝238.6Hz),-1.3。MS(EI):m/z(％)200(M+),185(100)。HRMS:理论值:C10H14SiF2(M+):200.0833；实测值:200.0838。
实施例25:化合物15
根据通用方法A，用0.3mmol芳基硼酸乙二醇酯投入反应得到(19F NMR产率:81％)。由于沸点较低，产物无法通过柱层析得到目标产物纯品，产物通过19F NMR和GC-MS分析来表征。19FNMR(376MHz,CDCl3)δ-113.6(d,J＝55.9Hz,2F)。GC-MS:m/z(％)162.0(M+)。
实施例26:化合物16
根据通用方法A，用0.3mmol芳基硼酸投入反应得到16(46mg,产率:77％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝10:1)，为无色透明油状物。1H NMR(300MHz,CDCl3)δ8.13(d,J＝8.2Hz,2H),7.58(d,J＝8.2Hz,2H),6.69(t,J＝56.1Hz,1H),4.40(q,J＝7.1Hz,2H),1.41(t,J＝7.1Hz,3H)。19FNMR(376MHz,CDCl3)δ-112.2(d,J＝56.1Hz,2F)。13CNMR(100MHz,CDCl3)δ165.8,138.3(t,J＝22.4Hz),132.6,129.9,125.6(t,J＝6.1Hz),114.0(t,J＝239.7Hz),61.4,14.3。IR(薄膜法)vmax 2983,2930,1767,1723cm-1。MS(EI):m/z(％)200(M+),172,155(100),127,105。HRMS:理论值:C10H10O2F2(M+):200.0649；实测值:200.0651.
实施例27:化合物17
根据通用方法A，用0.3mmol芳基硼酸投入反应得到17(47mg,产率:78％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝10:1)，为无色透明油状物。1H NMR(400MHz,CDCl3)δ8.18-8.15(m,2H),7.71(d,J＝7.7Hz,1H),7.55(t,J＝7.7Hz,1H),6.69(t,J＝56.2Hz,1H),4.41(q,J＝7.1Hz,2H),1.41(t,J＝7.1Hz,3H)。19FNMR(376MHz,CDCl3)δ-111.2(d,J＝56.2Hz,2F)。13CNMR(100MHz,CDCl3)δ165.7,134.7(t,J＝22.8Hz),131.7(t,J＝1.7Hz),131.1,129.7(t,J＝5.7Hz),128.9,126.9(t,J＝6.3Hz),114.2(t,J＝239.4Hz),61.4,14.3。IR(薄膜法)vmax 2983,1766,1615cm-1.MS(EI):m/z(％)200(M+),172,155(100),127,107.HRMS:理论值:C10H10O2F2(M+):200.0649；实测值:200.0648。
实施例28:化合物18
根据通用方法A，用0.3mmol芳基硼酸乙二醇酯投入反应得到18(24mg,产率:46％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝10:1)，为无色透明油状物。1H NMR(300MHz,CDCl3)δ8.02(d,J＝8.1Hz,2H),7.59(d,J＝8.1Hz,2H),6.68(t,J＝56.1Hz,1H),2.62(s,3H)。19FNMR(282MHz,CDCl3)δ-112.7(d,J＝56.1Hz,2F)。13C NMR(100MHz,CDCl3)δ197.4,138.8,138.5(t,J＝22.1Hz),128.6,125.9(t,J＝6.0Hz),113.9(t,J＝238.2Hz),26.8。IR(薄膜法)vmax 3064,2967,1767,1689cm-1。MS(EI):m/z(％)170(M+),155(100).HRMS:理论值:C9H8OF2(M+):170.0543；实测值:170.0542。
实施例29:化合物19
根据通用方法A，用0.3mmol芳基硼酸乙二醇酯投入反应得到19(28mg,产率:55％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝8:1)，为无色透明油状物。1H NMR(400MHz,CDCl3)δ8.08(s,1H),8.06(d,J＝7.6Hz,1H),7.71(d,J＝7.6Hz,1H),7.57(t,J＝7.7Hz,1H),6.68(t,J＝56.2Hz,1H),2.63(s,3H)。19FNMR(376MHz,CDCl3)δ-111.3(d,J＝56.2Hz,2F)。13C NMR(100MHz,CDCl3)δ197.1,137.5,134.9(t,J＝22.7Hz),130.5,129.9(t,J＝5.8Hz),129.2,125.5(t,J＝6.2Hz),114.1(t,J＝239.5Hz),26.7。MS(EI):m/z(％)170(M+),149,155(100),127,110。IR(薄膜法)vmax 3062,2968,1760,1690cm-1。HRMS:理论值:C9H8OF2(M+):170.0543；实测值:170.0539.
实施例30:化合物20
根据通用方法A，用0.3mmol芳基硼酸乙二醇酯投入反应得到20(26mg,产率:55％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝10:1)，为无色透明油状物。1H NMR(400MHz,CDCl3)δ10.06(s,1H),7.96(d,J＝8.0Hz,2H),7.68(d,J＝8.0Hz,2H),6.71(t,J＝56.0Hz,1H)。19FNMR(376MHz,CDCl3)δ-112.6(d,J＝56.0Hz,2F)。13C NMR(125MHz,CDCl3)δ191.4,139.7(t,J＝22.4Hz),137.9(t,J＝1.8Hz),129.9,126.3(t,J＝6.1Hz),113.8(t,J＝240.1Hz)。MS(EI):m/z(％)156(M+),156(100)。IR(薄膜法)vmax 3064,2967,1767,1689cm-1。HRMS:理论值:C8H6OF2(M+):156.0387；实测值:156.0384。
实施例31:化合物21
根据通用方法A，用0.3mmol芳基硼酸乙二醇酯投入反应得到21(24mg,产率:50％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝10:1)，为无色透明油状物。1H NMR(400MHz,CDCl3)δ10.06(s,1H),8.02(s,1H),8.0(d,J＝7.6Hz,1H),7.78(d,J＝7.6Hz,1H),7.65(t,J＝7.6Hz,1H),6.72(t,J＝56.1Hz,1H)。19FNMR(376MHz,CDCl3)δ-111.7(d,J＝56.1Hz,2F)。13C NMR(100MHz,CDCl3)δ191.3,136.6,135.5(t,J＝23.1Hz),131.8(t,J＝1.4Hz),131.3(t,J＝5.7Hz),129.6,126.8(t,J＝6.2Hz),113.8(t,J＝239.8Hz)。MS(EI):m/z(％)156(M+),155(100)。IR(薄膜法)vmax 3064,2967,1767,1689cm-1。HRMS:理论值:C8H6OF2(M+):156.0387；实测值:156.0390。
实施例32:化合物22
根据通用方法A，用0.3mmol芳基硼酸乙二醇酯投入反应得到22(28mg,产率:60％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝20:1)，为无色透明油状物。1H NMR(400MHz,CDCl3)δ7.77(d,J＝8.1Hz,2H),7.64(d,J＝8.1Hz,2H),6.69(t,J＝55.8Hz,1H)。19FNMR(376MHz,CDCl3)δ-113.2(d,J＝55.8Hz,2F)。13C NMR(100MHz,CDCl3)δ138.5(t,J＝22.9Hz),132.6,126.4(t,J＝6.1Hz),117.9,114.8(t,J＝2.0Hz),113.3(t,J＝240.7Hz)。IR(薄膜法)vmax3433,2961,2874,2232,1727cm-1。MS(EI):m/z(％)153(M+),152(100),134,103。HRMS:理论值:C8H5NF2(M+):153.0390；实测值:153.0389。
实施例33:化合物23
根据通用方法A，用0.3mmol芳基硼酸乙二醇酯投入反应得到23(39mg,产率:85％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝20:1)，为无色透明油状物。1H NMR(500MHz,CDCl3)δ7.82(s,1H),7.78(dd,J＝12.5Hz,7.9Hz,1H),7.62(t,J＝7.8Hz,1H),6.69(t,J＝55.9Hz,1H)。19FNMR(376MHz,CDCl3)δ-112.48(d,J＝55.9Hz,2F)。13C NMR(125MHz,CDCl3)δ135.7(t,J＝23.6Hz),134.2,129.9(t,J＝5.8Hz),129.7,129.3(t,J＝6.4Hz),117.8,113.2,113.1(t,J＝240.6Hz)。IR(薄膜法)vmax3433,2961,2874,2232,1727cm-1。MS(EI):m/z(％)153(M+),152(100),103.HRMS:理论值:C8H5NF2(M+):153.0390；实测值:153.0389。
实施例34:化合物24
根据通用方法A，用0.3mmol芳基硼酸乙二醇酯投入反应得到24(32mg,产率:60％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝20:1)，为无色透明油状物。1H NMR(400MHz,CDCl3)δ8.39(s,1H),8.36(d,J＝8.0Hz,1H),7.86(d,J＝7.6Hz,1H),7.68(t,J＝8.0Hz,1H),6.75(t,J＝55.9Hz,1H)。19FNMR(376MHz,CDCl3)δ-112.2(d,J＝55.9Hz,2F)。13CNMR(100MHz,CDCl3)δ148.3,136.1(t,J＝23.6Hz),131.5(t,J＝5.7Hz),130.1,125.6,121.0(t,J＝6.5Hz),113.1(t,J＝240.8Hz)。
实施例35:化合物25
根据通用方法A，用0.3mmol芳基硼酸投入反应得到25(25mg,产率:54％；19F NMR产率:70％)。产物通过硅胶柱柱层析纯化(正戊烷)，为无色透明油状物。
产物后处理方法:反应混合物用5mL食盐水稀释,再用2mL正戊烷萃取两次。合并所得的有机相再用适量饱和食盐水洗涤三次后直接柱层析。
1H NMR(400MHz,CDCl3)δ7.48(s,4H),6.64(t,J＝56.5Hz,1H),5.83(d,J＝17.6Hz,1H),5.35(d,J＝10.9Hz,1H)。19FNMR(376MHz,CDCl3)δ-110.5(d,J＝56.5Hz,2F)。13C NMR(125MHz,CDCl3)δ134.0(t,J＝2.1Hz),136.0,133.6(t,J＝22.4Hz),126.4,125.8(t,J＝6.1Hz),115.6,114.6(t,J＝238.4Hz)。IR(薄膜法)vmax3154,3093,2926,2854,2253,1632cm-1。MS(EI):m/z(％)154(M+,100),127,104。HRMS:理论值:C9H8F2(M+):154.0594；实测值:154.0591。
实施例36:化合物26
根据通用方法B，用0.3mmol芳基硼酸新戊二醇酯投入反应得到26(125mg,产率:81％；19F NMR产率:95％)。产物通过硅胶柱柱层析纯化(正己烷)，为无色透明油状物。1HNMR(500MHz,CDCl3)δ7.57(d,J＝8.4Hz,2H),7.46(d,J＝8.4Hz,2H),6.64(t,J＝56.4Hz,1H),1.17(s,18H),1.15-1.14(m,3H)。19FNMR(376MHz,CDCl3)δ-111.2(d,J＝56.4Hz,2F)。13CNMR(125MHz,CDCl3)δ134.0(t,J＝22.5Hz),132.3,126.1(t,J＝2.1Hz),125.4(t,J＝6.1Hz),114.3(t,J＝239.1Hz),106.0,92.7,18.6,11.3。IR(薄膜法)vmax 2944,2892,2866,2158,1614,1463cm-1。MS(EI):m/z(％)308(M+),266,237,223,209,195(100),179.HRMS:理论值:C18H26F2Si(M+):308.1772；实测值:308.1775。
实施例37:化合物27
根据通用方法A，用0.3mmol芳基硼酸投入反应得到27(41mg,产率:85％)。产物通过硅胶柱柱层析纯化(正己烷/二氯甲烷＝3:1到1:1)，为无色透明油状物。1H NMR(400MHz,CDCl3)δ7.51(d,J＝8.4Hz,2H),7.45(d,J＝8.4Hz,2H),6.65(t,J＝56.5Hz,1H),4.75(s,2H),1.80(s,1H)。19FNMR(376MHz,CDCl3)δ-110.34(d,J＝56.5Hz,2F)。13C NMR(100MHz,CDCl3)δ143.6,133.6(t,J＝22.5Hz),127.0,125.8(t,J＝6.1Hz),114.6(t,J＝238.5Hz),64.7。IR(薄膜法)vmax3676,3649,3567,3062,2962,2847,1706,1618cm-1。MS(EI):m/z(％)158(M+),127(100),107,77。
实施例38:化合物28
根据通用方法A，用0.3mmol芳基硼酸投入反应得到28(48mg,产率:90％)。产物通过硅胶柱柱层析纯化(正己烷)。1H NMR(400MHz,CDCl3)δ7.99(s,1H),7.96-7.89(m,3H),7.63(d,J＝8.8Hz,1H),7.59-7.57(m,2H),6.83(t,J＝56.4Hz,1H)。19FNMR(376MHz,CDCl3)δ-109.8(d,J＝56.4Hz,2F)。13CNMR(125.7MHz,CDCl3)δ134.3(t,J＝1.4Hz),132.6,131.6(t,J＝22.4Hz),128.9,128.5,127.9,127.4,126.8,125.9(t,J＝7.5Hz),122.0(t,J＝4.8Hz),115.1(t,J＝238.5Hz)。MS(EI):m/z(％)178(M+)(100),177,159,155,128。HRMS:理论值:C11H8F2(M+):178.0594；实测值:178.0598。
实施例39:化合物29
根据通用方法A，用0.3mmol芳基硼酸投入反应得到29(51mg,产率:95％)。产物通过硅胶柱柱层析纯化(正己烷)。1H NMR(400MHz,CDCl3)δ8.19(d,J＝8.2Hz,1H),7.97(d,J＝8.3Hz,1H),7.94-7.90(m,1H),7.70(m,1H),7.65-7.55(m,2H),7.51(t,J＝7.7Hz,1H),7.15(t,J＝55.2Hz,1H)。19FNMR(376MHz,CDCl3)δ-110.9(d,J＝55.2Hz,2F)。3C NMR(100MHz,CDCl3)δ133.8,131.5(t,J＝1.6Hz),129.7(t,J＝2.8Hz),129.5(t,J＝20.6Hz),128.8,127.2,126.4,124.8(t,J＝8.6Hz),124.7,123.6,115.4(t,J＝238.4Hz)。MS(EI):m/z(％)178(M+),115,87(100)。HRMS:理论值:C11H8F2(M+):178.0594；实测值:178.0597。
实施例40:化合物30
根据通用方法A，用0.3mmol芳基硼酸投入反应得到30(64mg,产率:93％)。产物通过硅胶柱柱层析纯化(正己烷)，产物为白色固体，其沸点为116-118℃。1H NMR(400MHz,CDCl3)δ8.70(dd,J＝8.4Hz,J＝1.6Hz,1H),8.64(d,J＝8.4Hz,1H),8.20-8.18(m,1H),7.93(s,1H),7.89(d,J＝8.4Hz,1H),7.72-7.58(m,4H),7.12(t,J＝55.2Hz,1H)。19FNMR(376MHz,CDCl3)δ-111.7(d,J＝55.2Hz,2F)。13C NMR(100MHz,CDCl3)δ131.4,130.9,130.2,129.5,128.3,128.0(t,J＝20.5Hz),127.9(t,J＝1.8Hz),127.2,127.15,127.13,126.8(t,J＝9.4Hz),124.5(t,J＝1.6Hz),123.3,122.7,115.7(t,J＝237.1Hz)。MS(EI):m/z(％)228(M+)(100),207,178,152,89。HRMS:理论值:C15H10F2(M+):228.0751；实测值:228.0752。
实施例41:化合物31
根据通用方法A，用0.3mmol芳基硼酸投入反应得到31(68mg,产率:92％)。产物通过硅胶柱柱层析纯化(正己烷)，产物为白色固体，其沸点为60-62℃。1H NMR(400MHz,CDCl3)δ7.80-7.76(m,2H),7.61(s,1H),7.50-7.46(m,2H),7.39-7.37(m,2H),6.73(t,J＝56.7Hz,1H),1.52(s,6H)。19FNMR(376MHz,CDCl3)δ-109.0(d,J＝56.7Hz,2F)。13C NMR(100MHz,CDCl3)δ154.09,154.08,141.8(t,J＝2.0Hz),138.2,133.2(t,J＝22.0Hz),128.1,127.2,124.8(t,J＝6.3Hz),122.8,120.6,120.1,119.9(t,J＝5.9Hz),115.3(t,J＝238.4Hz),47.1,27.0。IR(薄膜法)vmax3018,3064,2963,2862,1918,1618cm-1。MS(EI):m/z(％)244(M+),229(100),209,193,178,152。HRMS:理论值:C16H14F2(M+):244.1064；实测值:244.1071。
实施例42:化合物32
根据通用方法A，用0.3mmol芳基硼酸投入反应得到32(47mg,产率:71％)。产物通过硅胶柱柱层析纯化(正己烷)，产物为无色透明液体。1HNMR(400MHz,CDCl3)δ8.05(ddt,J＝7.6Hz,J＝1.2Hz,J＝1.2Hz,1H),7.97(ddt,J＝7.6Hz,J＝1.2Hz,J＝1.2Hz,1H),7.67(dd,J＝7.6Hz,1.0Hz,1H),7.63(d,J＝8.3Hz,1H),7.51(td,J＝7.6,1.2Hz,1H),7.44-7.37(m,2H),7.23(t,J＝55.2Hz,1H)。19FNMR(376MHz,CDCl3)δ-113.1(d,J＝55.2Hz,2F)。13C NMR(101MHz,CDCl3)δ156.3,127.8,125.1,123.7(t,J＝5.7Hz),123.4,123.2,123.1(t,J＝1.6Hz),122.7,120.8,118.5(t,J＝23.8Hz),111.9,111.8(t,J＝237.4Hz)。MS(EI):m/z(％)218(M+),218(100),199,168,139。HRMS:理论值:C13H8OF2(M+):218.0543；实测值:218.0546。
实施例43:化合物33
根据通用方法A，用0.3mmol芳基硼酸投入反应得到33(52mg,产率:73％)。产物通过硅胶柱柱层析纯化(正己烷)，产物为无色透明液体。1HNMR(400MHz,CDCl3)δ8.25(d,J＝7.9Hz,1H),8.19-8.17(m,1H),7.90-7.88(m,1H),7.62(d,J＝7.4Hz,1H),7.55-7.48(m,3H),6.94(t,J＝55.6Hz,1H)。19FNMR(376MHz,CDCl3)δ-113.3(d,J＝55.6Hz,2F)。13C NMR(125.7MHz,CDCl3)δ139.5(t,J＝1.0Hz),136.9,136.6(t,J＝3.3Hz),134.6,128.5(t,J＝22.8Hz),127.3,124.7,124.4,124.3(t,J＝7.0Hz),123.7(t,J＝1.8Hz),122.6,121.6,114.4(t,J＝239.4Hz)。MS(EI):m/z(％)234(M+),215,184(100),170,139。HRMS:理论值:C13H8SF2(M+):234.0315；实测值:234.0310。
实施例44:化合物34
根据通用方法A，用0.3mmol芳基硼酸投入反应或者通用方法B，用0.5mmol芳基硼酸新戊二醇酯投入反应得到34(ArB(OH)2:80mg,产率:72％；Ar-Bneop:167mg,产率:90％)。产物通过硅胶柱柱层析纯化(正己烷)，产物为灰白色固体，其沸点为128-130℃。1H NMR(400MHz,CDCl3)δ8.41(d,J＝8.4Hz,1H),8.35(d,J＝8.4Hz,1H),8.05(s,1H),7.91(d,J＝7.7Hz,1H),7.71(d,J＝8.3Hz,2H),7.63(d,J＝8.6Hz,1H),7.54(t,J＝7.8Hz,1H),7.39(t,J＝7.5Hz,1H),7.10(d,J＝8.1Hz,2H),6.80(t,J＝56.6Hz,1H),2.25(s,3H)。19FNMR(376MHz,CDCl3)δ-108.8(d,J＝56.6Hz,2F)。13C NMR(125.7MHz,CDCl3)δ145.2,139.5,138.7,134.7,130.0(t,J＝22.7Hz),129.7,128.0,126.4,125.6,124.6(t,J＝5.9Hz),124.1,120.2,117.5(t,J＝6.3Hz),115.2,115.0,114.8(t,J＝238.8Hz),21.4。MS(EI):m/z(％)371(M+),352,216(100),197,155,91。HRMS:理论值:C20H15NO2SF2(M+):371.0792；实测值:371.0791。
实施例45:化合物35
根据通用方法B，用0.5mmol芳基硼酸新戊二醇酯投入反应得到35(149mg,产率:85％)。产物通过硅胶柱柱层析纯化(正己烷/二氯甲烷＝2：1)，产物为灰白色固体，其沸点为86-88℃。1H NMR(400MHz,DMSO-d6,80℃):δ7.75(s,1H),7.57(dd,J＝8.0,2.8Hz,2H),7.43(t,J＝5.9Hz,2H),7.36(t,J＝7.2Hz,1H),7.25(t,J＝7.4Hz,1H),7.02(t,J＝55.8Hz,1H),1.45(s,9H)。19FNMR(376MHz,CDCl3)δ-110.5(d,J＝56.4Hz,2F)。13C NMR(101MHz,DMSO-d6,80℃)δ151.1,138.3,137.7,134.2,132.7(t,J＝22.6Hz),130.2,127.5,127.02,126.99,126.8,126.2,124.2(t,J＝6.4H),123.2(t,J＝5.9Hz),114.0(t,J＝235.4Hz),81.8,27.4。IR(薄膜法)vmax3064,2980,2930,1709,1607cm-1.MS(EI):m/z(％)349(M+),293,250,243,199,57(100)。HRMS:理论值:C18H17NO2SF2(M+):349.0948；实测值:349.0943。
实施例46:化合物36
根据通用方法A，用0.3mmol芳基硼酸投入反应得到36(63mg,产率:89％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝10:1到4:1)，为无色透明油状物。1H NMR(400MHz,CDCl3)δ8.31(s,1H),7.75(dd,J＝8.6,2.3Hz,1H),7.49-7.47(m,2H),7.43-7.34(m,3H),6.89(d,J＝8.6Hz,1H),6.65(t,J＝56.0Hz,1H),5.44(s,2H)。19FNMR(376MHz,CDCl3)δ-109.6(d,J＝56.0Hz,2F)。13C NMR(125.7MHz,CDCl3)δ165.1,145.1(t,J＝7.4Hz),136.7,135.9(t,J＝4.5Hz),128.5,128.00,127.99,123.6(t,J＝23.3Hz),113.7(t,J＝237.6Hz),111.4,68.0。IR(薄膜法)vmax3068,3034,2957,2888,2850,1615,1578cm-1。MS(EI):m/z(％)235(M+),129,91(100)。HRMS:理论值:C13H11NOF2(M+):235.0809；实测值:235.0804。
实施例47:化合物37
根据通用方法A，用0.3mmol芳基硼酸投入反应得到37(39mg,产率:60％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝10:1到4:1)，为无色透明油状物。1H NMR(400MHz,CDCl3)δ8.27(s,1H),7.63(d,J＝8.8Hz,1H),6.66(d,J＝8.8Hz,1H),6.58(t,J＝56.3Hz,1H),3.82-3.80(m,4H),3.59-3.57(m,4H)。19FNMR(376MHz,CDCl3)δ-108.7(d,J＝56.3Hz,2F)。13C NMR(101MHz,CDCl3)δ160.4,146.0,134.9(t,J＝4.4Hz),119.6(t,J＝23.4Hz),114.2(t,J＝236.6Hz),106.3,66.6,45.2。MS(EI):m/z(％)214(M+),183,129(100)。IR(薄膜法)vmax2996,2968,2899,1614cm-1。HRMS:理论值:C10H12N2OF2(M+):214.0918；实测值:214.0916。
实施例48:化合物38
根据通用方法A，用0.3mmol芳基三异丙氧基硼酸酯锂盐(Xiao,Y.-L.Min,Q.-Q.Xu,C.Wang,R.-W.Zhang,X.Angew.Chem.Int.Ed.2016,55,5873-5841)投入反应得到38(29mg,产率:50％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝10:1到4:1)，为无色透明油状物。1H NMR(400MHz,CDCl3)δ8.08(dd,J＝8.5Hz,5.6Hz,2H),7.90(d,J＝1.1Hz,1H),7.77(dd,J＝8.8Hz,1.5Hz,1H),7.33(d,J＝8.5Hz,1H),6.79(t,J＝56.3Hz,1H),2.75(s,3H)。19FNMR(376MHz,CDCl3)δ-110.3(d,J＝56.3Hz,2F)。13C NMR(125.7MHz,CDCl3)δ160.7,148.6,136.6,131.5(t,J＝22.5Hz),129.6,125.74(t,J＝4.9Hz),125.7,125.4(t,J＝7.3Hz),122.9,114.5(t,J＝238.9Hz),25.4。IR(薄膜法)vmax2998,2360,1631,1603cm-1。MS(EI):m/z(％)193(M+)(100),178,143。HRMS:理论值:C11H9NF2(M+):193.0703；实测值:193.0698。
实施例49:化合物39
根据通用方法B，用0.5mmol芳基硼酸新戊二醇酯39a投入反应得到39(80mg,产率:65％yield)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝10:1)，产物为灰白色固体，其沸点为119-121℃。1H NMR(500MHz,CDCl3)δ8.36(d,J＝8.5Hz,2H),7.81-7.79(m,1H),7.68(d,J＝8.2Hz,2H),7.62-7.60(m,1H),7.41-7.37(m,2H),6.73(t,J＝56.2Hz,1H)。19FNMR(282MHz,CDCl3)δ-112.3(d,J＝56.2Hz,2F)。13C NMR(125MHz,CDCl3)δ162.0,150.8,142.0,137.0,129.4(t,J＝2.0Hz),127.9,126.2(t,J＝6.1Hz),125.6,124.8,120.3,114.1(t,J＝239.6Hz),110.7。IR(薄膜法)vmax 3051,2925,1711,1654,1606cm-1。MS(EI):m/z(％)245(M+)(100),217,195,127,92,63。HRMS:理论值:C14H9NOF2(M+):245.0652；实测值:245.0658。
实施例50:化合物40
根据通用方法B，用0.5mmol芳基硼酸新戊二醇酯40a投入反应得到40(61mg,产率:58％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝10:1)，产物为无色透明油状物。1HNMR(400MHz,CDCl3)δ7.67(s,1H),7.54(s,1H),7.39-7.34(m,3H),7.25-7.23(m,2H),6.68(t,J＝56.8Hz,1H),5.31(s,2H)。19FNMR(376MHz,CDCl3)δ-106.4(d,J＝56.8Hz,2F).13C NMR(125MHz,CDCl3)δ137.2(t,J＝4.6Hz),135.5,129.0,128.4,128.0(t,J＝5.7Hz),127.9,117.5(t,J＝26.9Hz),110.9(t,J＝233.9Hz),56.4。IR(thin film)vmax3091,3032,2960,1733,1652,1574cm-1。MS(EI):m/z(％)208(M+),207,187,131,91(100),65。HRMS:理论值:C11H10N2F2(M+):208.0812；实测值:208.0804。
实施例51:化合物41
根据通用方法A，用0.5mmol芳基硼酸乙二醇酯SI-5投入反应得到41(201mg,从SI-4(Tang,P.Furuya,T.Ritter,T.J.Am.Chem.Soc.2010,132,12150-12154.)计算的两步产率:92％)。产物通过硅胶柱柱层析纯化(正己烷)，产物为无色透明油状物。
制备芳基硼酸乙二醇酯SI-5的步骤:无水无氧下，向20mL Schlenk管中加入无水KOAc(1.5mmol,147.5mg,3.0当量),B2(OH)4(1mmol,90mg,2.0当量),Xphos(1mol％),XPhosPd-G1(0.5mol％)和SI-4(0.5mmol,267.4mg,1.0当量),以及乙二醇(2mmol,124mg,4.0当量)和新蒸乙醇(5mL)。反应混合物加热至80度搅拌反应4小时后冷却至室温并浓缩。所得混合物用二氯甲烷20mL稀释后用适量饱和食盐水洗涤。有机相无水硫酸镁干燥后浓缩得SI-5，产物不经纯化直接投入下一步反应。
41的数据表征:1H NMR(400MHz,CDCl3)δ7.10(s,1H),7.06(s,1H),6.53(t,J＝57.0Hz,1H),2.78(t,J＝6.4Hz,2H),2.19(s,3H),1.81(ddd,J＝20.7,13.7,7.0Hz,2H),1.61-1.04(m,25H),0.89-0.85(m,12H)。19FNMR(376MHz,CDCl3)δ-107.3(d,J＝57.0Hz,2F)。13C NMR(100MHz,CDCl3)δ154.1(t,J＝1.8Hz),126.8,125.4(t,J＝5.7Hz),124.7(t,J＝45.0Hz),124.4(t,J＝6.1Hz),120.5,115.4(t,J＝236.8Hz),76.7,40.1,39.4,37.44,37.40,37.38,37.28,32.8,32.7,30.9,28.0,24.8,24.4,24.2,22.7,22.6,22.2,20.9,19.7,19.6,16.1。IR(薄膜法)vmax2927,2867,1484,1381cm-1。MS(EI):m/z(％)436(M+),211(100),171.HRMS:理论值:C28H46OF2(M+):436.3517；实测值:436.3519。
实施例52:化合物42
根据通用方法A，80度下用0.5mmol芳基硼酸乙二醇酯SI-7投入反应60小时得到42(164mg,从SI-6(Tang,P.Furuya,T.Ritter,T.J.Am.Chem.Soc.2010,132,12150-12154.)计算的两步产率:74％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝4:1)，产物为白色固体，其熔点为144-146℃。
制备芳基硼酸乙二醇酯SI-7的步骤:无水无氧下，向20mL Schlenk管中加入无水KOAc(1.5mmol,147.5mg,3.0当量),B2(OH)4(1mmol,90mg,2.0当量),Xphos(1mol％),XPhosPd-G1(0.5mol％)和SI-6(0.5mmol,270.8mg,1.0当量),以及乙二醇(2mmol,124mg,4.0当量)和新蒸乙醇(5mL)。反应混合物加热至80度搅拌反应4小时后冷却至室温并浓缩。所得混合物用二氯甲烷20mL稀释后用适量饱和食盐水洗涤。有机相无水硫酸镁干燥后浓缩得SI-7，产物不经纯化直接投入下一步反应。
42的数据表征:1H NMR(400MHz,CDCl3)δ7.53(d,J＝7.9Hz,2H),7.41(d,J＝8.0Hz,2H),7.29(m,2H),7.23-7.19(m,2H),7.02(t,J＝8.6Hz,2H),6.94(t,J＝8.6Hz,2H),6.64(t,J＝56.4Hz,1H),4.72(m,1H),4.68(d,J＝2.4Hz,1H),3.08(td,J＝6.8Hz,2.4Hz,1H),2.16(d,J＝3.2Hz,1H),2.06-1.87(m,4H)。19FNMR(376MHz,CDCl3)δ-111.0(d,J＝56.4Hz,2F),-114.7(m,1F),-117.7(m,1F)。13C NMR(100MHz,CDCl3)δ167.0,162.2(d,J＝245.8Hz),159.1(d,J＝243.8Hz),140.4(t,J＝2.0Hz),139.9(d,J＝3.1Hz),134.8(t,J＝22.7Hz),133.6(d,J＝2.8Hz),127.4(d,J＝8.1Hz),126.6(t,J＝6.0Hz),126.2,118.3(d,J＝7.9Hz),116.0(d,J＝22.7Hz),115.4(d,J＝21.4Hz),114.2(t,J＝239.1Hz),73.2,60.9,60.5,36.6,25.1。
实施例53:化合物43
根据通用方法A，用0.5mmol芳基硼酸SI-8(Feng,Z.Min,Q.-Q.Xiao,Y.-L.Zhan,B.Zhang,X.Angew.Chem.,Int.Ed.2014,53,1669-1673)投入反应得到43(107mg,产率:70％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝4:1)，产物为白色固体，其熔点为59-62℃。1H NMR(400MHz,CDCl3)δ7.38(d,J＝8.4Hz,1H),7.28(d,J＝8.4Hz,1H),7.24(s,1H),6.58(t,J＝56.6Hz,1H),2.97-2.94(m,2H),2.51(q,J＝8.8Hz,1H),2.47-2.42(m,1H),2.32(t,J＝10.0Hz,1H),2.19-2.12(m,1H),2.10-2.03(m,2H),1.99-1.96(m,1H),1.67-1.42(m,6H),0.91(s,3H)。19FNMR(376MHz,CDCl3)δ-110.0(dd,J＝56.6Hz,J＝5.4Hz,2F)。13CNMR(125.7MHz,CDCl3)δ220.5,142.5(t,J＝1.9Hz),137.0,131.8(t,J＝22.5Hz),126.0(t,J＝5.9Hz),125.6,122.7(t,J＝6.0Hz),114.8(t,J＝238.1Hz),50.4,47.8,44.3,37.8,35.7,31.4,29.2,26.2,25.5,21.5,13.7。
实施例54:化合物44
根据通用方法A，用0.5mmol芳基硼酸SI-9(Xiao,Y.-L.Guo,W.-H.He,G.-Z.Pan,Q.Zhang,X.Angew.Chem.,Int.Ed.2014,53,9909-9913)投入反应得到44(69mg,产率:50％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝4:1)，产物为白色固体，其熔点为61-63℃。1H NMR(400MHz,CDCl3)δ7.94(dd,J＝8.4Hz,1.5Hz,1H),7.59(s,4H),7.52(td,J＝8.4Hz,J＝1.6Hz,1H),7.09(m,2H),6.68(t,J＝56.4Hz,1H),5.54(dd,J＝13.1Hz,3.1Hz,1H),3.06(dd,J＝16.9Hz,13.1Hz,1H),2.90(dd,J＝16.9Hz,3.1Hz,1H)。19F NMR(376MHz,CDCl3)δ-110.9(d,J＝56.4Hz,2F)。13C NMR(100MHz,CDCl3)δ191.4,161.3,141.5(t,J＝1.8Hz),136.3,134.7(t,J＝22.4Hz),127.1,126.4,126.1(t,J＝6.0Hz),121.9,120.9,118.0,114.4(t,J＝239.0Hz),78.9,44.6。IR(薄膜法)vmax3353,2923,2853,1683,1601,1465cm-1。MS(EI):m/z(％)274(M+),257,147,120(100),92.HRMS:理论值:C16H12O2F2(M+):274.0805；实测值:274.0794。
实施例55:化合物45
根据通用方法B，用0.5mmol芳基硼酸新戊二醇酯45a投入反应得到45(186mg,产率：90％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝6:1)，产物为无色透明油状物。1H NMR(500MHz,CDCl3)δ8.11(d,J＝8.1Hz,2H),7.60(d,J＝8.1Hz,2H),6.69(t,J＝56.0Hz,1H),5.95(d,J＝3.7Hz,1H),5.51(d,J＝2.6Hz,1H),4.64(d,J＝3.7Hz,1H),4.33(m,2H),4.10(ddd,J＝13.1Hz,8.6Hz,5.0Hz,2H),1.56(s,3H),1.41(s,3H),1.32(s,3H),1.26(s,3H)。19FNMR(376MHz,CDCl3)δ-112.4(d,J＝56.0Hz,2F).13C NMR(125MHz,CDCl3)δ164.3,138.9(t,J＝22.5Hz),131.7,130.0,125.8(t,J＝6.0Hz),113.8(t,J＝239.9Hz),112.4,109.4,105.1,83.3,79.9,76.95,72.5,67.3,26.8,26.7,26.1,25.1。IR(薄膜法)vmax2989,2938,2898,1730,1714,1457cm-1。MS(EI):m/z(％)399[(M-CH3)+],341,281,255,155(100),127,101。HRMS:理论值:C19H21O7F2[(M-CH3)+]:399.1255；实测值:399.1256。
实施例56:化合物46
根据通用方法A，用0.5mmol芳基硼酸乙二醇酯SI-11投入反应得到46(116mg,从SI-10计算的两步产率:70％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝4:1)，产物为白色固体，其熔点为70-73℃。
制备芳基硼酸乙二醇酯SI-11的步骤:无水无氧下，向20mL Schlenk管中加入无水KOAc(1.5mmol,147.5mg,3.0当量),B2(OH)4(1mmol,90mg,2.0当量),Xphos(2mol％),XPhosPd-G1(1mol％)和SI-10(0.5mmol,213.7mg mg,1.0当量),以及乙二醇(2mmol,124mg,4.0当量)和新蒸乙醇(5mL)。反应混合物加热至80度搅拌反应4小时后冷却至室温并浓缩。所得混合物用二氯甲烷20mL稀释后用适量饱和食盐水洗涤。有机相无水硫酸镁干燥后浓缩得SI-11，产物不经纯化直接投入下一步反应。
46的数据表征:1H NMR(500MHz,CDCl3)δ7.42(d,J＝7.9Hz,2H),7.21(d,J＝7.9Hz,2H),6.60(t,J＝56.5Hz,1H),5.03(d,J＝7.5Hz,1H),4.60(dd,J＝13.0Hz,6.1Hz,1H),3.70(s,3H),3.17(dd,J＝13.7Hz,5.5Hz,1H),3.06(dd,J＝13.6,6.1Hz,1H),1.40(s,9H)。19FNMR(376MHz,CDCl3)δ-110.5(d,J＝56.5Hz,2F)。13C NMR(125MHz,CDCl3)δ172.0,154.9,139.0(t,J＝2.0Hz),133.0(t,J＝22.0Hz),129.6,125.7(t,J＝5.9Hz),114.6(t,J＝238.5Hz),80.0,54.2,52.2,38.1,28.2。
实施例57:化合物47
根据通用方法B，用0.5mmol芳基硼酸新戊二醇酯47a投入反应得到47(120mg,产率：60％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝4:1)，产物为无色透明油状物。1H NMR(400MHz,CDCl3)旋转异构混合物:δ8.09(d,J＝8.1Hz,2H),7.59(d,J＝8.0Hz,2H),6.69(t,J＝56.1Hz,1H),5.55-5.52(m,1H),4.53和4.43(t,J＝8.0Hz,1H,旋转异构体),3.88-3.84(m,2H),3.77和3.76(s,3H,旋转异构体),2.58-2.50(m,1H),2.37-2.30(m,1H),1.45和1.43(s,9H,旋转异构体)。19F NMR(376MHz,CDCl3)δ-112.4(d,J＝56.1Hz,2F)。13CNMR(100MHz,CDCl3)旋转异构混合物,其中括号中的核磁数据是旋转异构混合物中的少数:δ173.0(172.7),165.05(165.01),154.2(153.6),138.9(138.8),131.8(131.7),130.0,125.73(125.70)(t,J＝5.9Hz),113.8(t,J＝239.8Hz),86.7,73.7(73.0),57.9(57.6),52.4(54.3),52.2(52.0),36.7(35.6),28.3(28.2)。IR(薄膜法)vmax2978,2931,1751,1701,1583cm-1。MS(EI):m/z(％)326[(M-OC4H9)+],155,127(100)。HRMS:理论值:C15H14NO5F2[(M-OC4H9)+]:326.0840；实测值:326.0827。
实施例58:化合物48
根据通用方法B，用0.5mmol芳基硼酸新戊二醇酯48a投入反应得到48(151mg,产率：80％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝6:1)，产物为无色透明油状物。1H NMR(400MHz,CDCl3)δ7.81(d,J＝7.8Hz,2H),7.75(d,J＝9.0Hz,2H),7.62(d,J＝8.0Hz,2H),6.86(d,J＝8.9Hz,2H),6.72(t,J＝56.2Hz,1H),5.09(hept,J＝6.2Hz,1H),1.66(s,6H),1.20(d,J＝6.3Hz,6H)。19FNMR(376MHz,CDCl3)δ-111.9(d,J＝56.2Hz,2F)。13C NMR(100MHz,CDCl3)δ194.6,173.1,159.9,140.3,137.3(t,J＝22.5Hz),132.1,130.0,129.9,125.5(t,J＝6.0Hz),117.2,114.1(t,J＝239.6Hz),79.4,69.3,25.3,21.5。IR(薄膜法)vmax2983,2925,1730,1654cm-1。MS(EI):m/z(％)376(M+),289(100),248,121。HRMS:理论值:C21H22O4F2:376.1486；实测值:376.1472。
实施例59:化合物49
根据通用方法B，用0.5mmol芳基硼酸新戊二醇酯49a投入反应得到49(117mg,产率：90％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝8:1)，产物为无色透明油状物。1H NMR(400MHz,CDCl3)δ7.38(d,J＝8.2Hz,2H),6.87(d,J＝8.2Hz,2H),6.58(t,J＝56.7Hz,1H),4.23(q,J＝7.1Hz,2H),1.62(s,6H),1.23(t,J＝7.1Hz,3H)。19FNMR(376MHz,CDCl3)δ-108.9(d,J＝56.7Hz,2F)。13C NMR(100MHz,CDCl3)δ173.9,157.4(t,J＝1.9Hz),127.7(t,J＝22.7Hz),126.7(t,J＝6.0Hz),118.3,114.7(t,J＝237.7Hz),79.2,61.6,25.3,14.0。IR(薄膜法)vmax 2990,2942,1735,1615cm-1。MS(EI):m/z(％)258(M+),185(100),144,115。HRMS:理论值:C13H16O3F2:258.1068；实测值:258.1069。
实施例60:化合物49的克量级合成.
冰水浴下，向100mL封管中加入KOH(336mg,6mmol,1.0当量)和芳基硼酸新戊二醇酯49a(1.92g,6mmol,1.0当量)以及MeOH(24mL)和新蒸无水1,4-二氧六环(12mL)。零度下搅拌反应30分钟后,减压除去低沸点溶剂。随后，在无水无氧下加入无水K2CO3(粉末,2.48g,18mmol,3.0当量),1，4对苯二酚(1.32g,12mmol,2.0当量),Pd2(dba)3(82.4mg,0.09mmol,1.5mol％),和Xantphos(156.2mg,0.045mmol,4.5mol％),以及ClCF2H的无水1,4-二氧六环溶液(30mL,2.0M,10当量)和新蒸无水1,4-二氧六环(20mL)。盖上封管塞后加热至110℃(油浴)搅拌反应48小时。反应结束后冷却至室温，加入内标单氟苯(1.0当量)，19F NMR检测目标产物氟谱产率。所得混合物用250mL乙酸乙酯稀释适量饱和食盐水洗涤后无水硫酸镁干燥浓缩。目标产物49通过柱层析得到(1.12g,产率：72％)。
实施例61:化合物50
根据通用方法B，用0.5mmol芳基硼酸新戊二醇酯50a投入反应得到50(180mg,产率：92％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝8:1)，产物为无色透明油状物。1H NMR(400MHz,CDCl3)旋转异构混合物:δ7.33-7.30(m,5H),7.29-7.24和7.19-7.15(m,1H,旋转异构体),6.87和6.82(d,J＝8.0Hz,2H,旋转异构体),6.52(t,J＝56.8Hz,1H),5.16-5.14和5.11-5.10(m,1H,旋转异构体),3.46和3.36(br,2H,旋转异构体),2.85(s,3H),2.16(br,1H),2.12-2.04(m,1H),1.38(s,9H)。19F NMR(376MHz,CDCl3)δ-108.4(d,J＝56.8Hz,2F)。13C NMR(125MHz,CDCl3)旋转异构混合物,其中括号中的核磁数据是旋转异构混合物中的少数:δ159.7,155.7,141.0,129.2,128.7(128.6),127.7(127.5),126.9(t,J＝5.9Hz),125.6,(120.7)115.7,114.7(t,J＝237.4Hz),79.3(78.2),67.0,(45.8)45.7,37.2(36.7),34.4,28.3。IR(薄膜法)vmax 2976,1694,1615,1589cm-1。MS(EI):m/z(％)391(M+),318,248,214,192,144,88(100)。HRMS:理论值:C22H27NO3F2:391.1959；实测值:391.1956。
实施例62:化合物51和51′
根据通用方法B，用0.5mmol芳基硼酸新戊二醇酯51a投入反应得51和51′的混合物。所得混合物溶于甲醇，冰水浴下NaBH4(9.5mg,0.25mmol)还原1小时后浓缩，硅胶柱层析(正己烷/乙酸乙酯＝4:1to 2:1)纯化得到51(96mg,产率：48％)，产物为无色油状物。1HNMR(400MHz,CDCl3)δ8.40(d,J＝3.6Hz,1H),7.45(d,J＝7.6Hz,1H),7.31(d,J＝14.1Hz,2H),7.27(d,J＝9.0Hz,1H),7.10(dd,J＝7.7Hz,4.8Hz,1H),6.58(t,J＝56.5Hz,1H),4.13(q,J＝7.1Hz,2H),3.81(br,2H),3.49-3.34(m,2H),3.18-3.11(m,2H),2.91-2.83(m,2H),2.51-2.44(m,1H),2.37-2.30(m,3H),1.24(t,J＝7.1Hz,3H)。19FNMR(376MHz,CDCl3)δ-110.3(d,J＝56.5Hz,2F)。13C NMR(100MHz,CDCl3)δ156.7,155.5,146.6,141.8,138.3,137.7,134.4,133.41,133.36(t,J＝22.3Hz),129.6,126.1(t,J＝5.8Hz),123.3(t,J＝6.1Hz),122.3,114.6(t,J＝238.6Hz),61.3,44.8,44.7,31.7,31.5,30.7,30.5,14.6。IR(薄膜法)vmax 2979,2865,1697,1436cm-1。MS(EI):m/z(％)398(M+)(100),282。HRMS:理论值:C23H24N2O2F2:398.1806；实测值:398.1812。
化合物51′
分析纯的51′通过反向半制备柱纯化51和51′的混合物得到(MeCN/H2O＝50:50(v/v,含0.1％三氟乙酸)；柱型:Kaseisorb LC ODS 2000(10.0mm×250mm,5μm)；流动相流速:4.0mL/min；波长:220nm；温度:25℃)。1H NMR(400MHz,CDCl3)δ10.05(s,1H),8.86(d,J＝1.8Hz,1H),7.94(d,J＝1.8Hz,1H),7.33(d,J＝11.2Hz,2H),7.28(d,J＝8.2Hz,1H),6.59(t,J＝56.8Hz,1H),4.14(q,J＝7.1Hz,2H),3.81(br,2H),3.52-3.41(m,2H),3.21-3.17(m,2H),3.03-2.87(m,2H),2.55-2.48(m,1H),2.45-2.27(m,3H),1.25(t,J＝7.1Hz,3H)。19FNMR(376MHz,CDCl3)δ-110.6(d,J＝56.8Hz,2F)。13C NMR(100MHz,CDCl3)δ190.4,162.4,155.4,149.3,140.7,139.4,138.1,137.0,134.4,133.9(t,J＝22.4Hz),130.3,129.8,126.3(t,J＝5.9Hz),123.6(t,J＝6.3Hz),114.4(t,J＝238.8Hz),61.4,44.73,44.66,31.50,31.48,30.8,30.7,14.7。IR(薄膜法)vmax3502,2979,2914,2857,1697,1616,1434cm-1。MS(EI):m/z(％)426(M+)(100),398,336,324,310,296,273。HRMS:理论值:C24H24N2O3F2:426.1755；实测值:426.1759。
实施例63:化合物52
根据通用方法A，用0.5mmol芳基硼酸乙二醇酯52a投入反应得到52(88mg,产率：45％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝4:1)，产物为无色透明油状物。1HNMR(400MHz,CDCl3)δ7.80(d,J＝8.2Hz,2H),7.64(d,J＝8.2Hz,2H),6.96(d,J＝2.5Hz,1H),6.86(d,J＝9.0Hz,1H),6.74(t,J＝56.0Hz,1H),6.66(dd,J＝9.0Hz,2.5Hz,1H),3.84(s,3H),3.71(s,3H),3.67(s,2H),2.37(s,3H)。19FNMR(376MHz,CDCl3)δ-112.3(d,J＝56.0Hz,2F)。13C NMR(100MHz,CDCl3)δ171.3,168.4,156.1,138.2(t,J＝22.6Hz),137.9(t,J＝1.6Hz),135.9,130.7,129.9,126.0(t,J＝6.0Hz),115.1,113.8(t,J＝240.1Hz),112.8,111.6,110.9,101.3,55.7,52.2,30.1,13.5。IR(薄膜法)vmax3374,2954,2836,1736,1683cm-1。MS(EI):m/z(％)387(M+),328,233,174(100)。HRMS:理论值:C21H19NO4F2:387.1282；实测值:387.1288。
实施例64:化合物53
根据通用方法B，用0.5mmol芳基硼酸新戊二醇酯53a投入反应得到53(78mg,产率：72％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝4:1到2:1)，产物为无色透明油状物。1H NMR(400MHz,CDCl3)δ7.90(d,J＝8.1Hz,2H),7.64(d,J＝8.1Hz,2H),6.68(t,J＝55.9Hz,1H),6.61(s,1H),3.94(s,3H),3.85(s,3H),3.46(s,3H)。19FNMR(376MHz,CDCl3)δ-112.7(d,J＝55.9Hz,2F)。13C NMR(125MHz,CDCl3)δ172.7,164.3,161.2,140.9(t,J＝2.1Hz),139.0(t,J＝22.9Hz),127.6,126.5(t,J＝6.0Hz),113.3(t,J＝240.7Hz),90.2,54.8,54.2,34.6。IR(薄膜法)vmax3125,3020,1588cm-1。MS(EI):m/z(％)360.1(M+,100)。HRMS:理论值:C14H16N3O4F2S:360.0824；实测值:360.0820。
实施例65:化合物SI-12
根据文献方法(Ishiyama,T.Takagi,J.Ishida,K.Miyaura,N.Anastasi,N.R.Hartwig,J.H.J.Am.Chem.Soc.2002,124,390-391),无水无氧下，向25mL封管中加入N-Boc-Mexiletine(559mg,2mmol),Bpin-Bpin(315mg,1.24mmol),[Ir(COD)OMe]2(6.63mg,0.01mmol),4,4'-Bis(t-butyl)-2,2'-bipyridine(5.36mg,0.02mmol)和新蒸THF(10mL)。盖上封管塞后加热至80℃搅拌反应24小时(油浴)。反应冷却至室温后乙酸乙酯稀释后硅藻土过滤，所得滤液浓缩后硅胶柱层析(二氯甲烷/乙酸乙酯＝10:1)得SI-12(535mg,66％yield)。1H NMR(500MHz,CDCl3)δ7.48(s,2H),4.88(br,1H),3.99(br,1H),3.79(br,1H),3.69(dd,J＝9.0,3.5Hz,1H),2.26(s,6H),1.46(s,9H),1.37(d,J＝6.8Hz,3H),1.33(s,12H)。13C NMR(125MHz,CDCl3)δ157.9,155.3,135.7,130.3,83.7,79.3,74.0,46.7,28.4,24.8,17.9,16.0(硼取代的碳原子没有观测到)。IR(薄膜法)vmax2976,1715cm-1.MS(EI):m/z(％)405.3(M+),406.3(100)。HRMS:理论值:C22H37NO5B:405.2796；实测值:405.2791。
实施例66:化合物54a
无水无氧下，向25mL反应管中加入SI-12(365mg,0.90mmol),NH4OAc(416mg,5.4mmol),NaIO4(1.16g,5.4mmol),acetone(10mL)和H2O(5mL)。室温下搅拌反应48小时。反应结束后乙酸乙酯稀释后适量水洗三次，有机相无水硫酸镁干燥后浓缩。所得产物溶于二氯甲烷(20mL)和新戊二醇(1.8mmol,188mg,2.0当量)，搅拌反应24小时后硅藻土过滤，所得滤液浓缩后硅胶柱层析(二氯甲烷/乙酸乙酯＝10:1)得54a(321mg,从SI-12计算的两步产率：91％)。产物为白色固体，其熔点为157-159℃。1H NMR(500MHz,CDCl3)δ7.46(s,2H),4.92(br,1H),3.99(br,1H),3.78(br,1H),3.75(s,4H),3.69(dd,J＝9.0Hz,3.5Hz,1H),2.26(s,6H),1.46(s,9H),1.37(d,J＝6.8Hz,3H),1.01(s,6H)。13C NMR(125MHz,CDCl3)δ157.5,155.3,134.8,129.9,79.2,74.0,72.2,46.7,31.8,28.4,21.8,17.8,16.0(硼取代的碳原子没有观测到)。IR(薄膜法)vmax3407,2959,1722cm-1。MS(EI):m/z(％)391.3(M+),392.3(100)。HRMS:理论值:C21H35NO5B:381.2639；实测值:391.2639。
实施例67:化合物54
根据通用方法B，用0.5mmol芳基硼酸新戊二醇酯54a投入反应得到54(125mg,产率：76％)。产物通过硅胶柱柱层析纯化(正己烷/乙酸乙酯＝10:1)，产物为白色固体，其沸点为80-82℃。1H NMR(400MHz,CDCl3)δ7.15(s,2H),6.53(t,J＝56.7Hz,1H),4.84(br,1H),4.00(br,1H),3.79(br,1H),3.70(dd,J＝9.0Hz,3.5Hz,1H),2.29(s,6H),1.46(s,9H),1.38(d,J＝6.8Hz,3H)。19F NMR(376MHz,CDCl3)δ-109.2(d,J＝56.7Hz,2F)。13C NMR(100MHz,CDCl3)δ157.0(t,J＝2.2Hz),155.3,131.5,129.8(t,J＝22.2Hz),126.2(t,J＝5.9Hz),114.7(t,J＝238.0Hz),79.4,74.2,46.6,28.4,17.8,16.2。IR(薄膜法)vmax3451,3354,2977,2929,1705,1500cm-1。MS(EI):m/z(％)329(M+),273,236,172,102(100)。HRMS:理论值:C17H25NO3F2:329.1803；实测值:329.1796。
实施例68:化合物55a
根据文献方法(Tobisu,M.Kinuta,H.Kita,Y.Rémond,E.Chatani,N.J.Am.Chem.Soc.2012,134,115-118),无水无氧下，向25mL封管中加入cyhalofop-butyl(1.0g,2.8mmol),bis(neopentylglycolato)diboron(1.9g,8.4mmol),[RhCl(cod)]2(69mg,0.14mmol),Xantphos(324mg,0.56mmol),DABCO(628mg,5.6mmol),和新蒸甲苯(5.6mL)。盖上封管塞后加热至100℃搅拌反应96小时(油浴)。反应冷却至室温后乙酸乙酯稀释后硅藻土过滤，所得滤液浓缩后硅胶柱层析(正己烷/乙酸乙酯＝6:1to 3:1)得55a(1.02g,产率：82％)。1H NMR(300MHz,CDCl3)δ7.55(d,J＝11.5Hz,1H),7.45(d,J＝8.0Hz,1H),6.96-6.83(m,5H),4.70(q,J＝6.7Hz,1H),4.22-4.09(m,2H),3.75(s,4H),1.62(d,J＝6.7Hz,3H),1.62-1.57(m,2H),1.34-1.27(m,2H),1.01(s,6H),0.89(t,J＝7.4Hz,3H)。19FNMR(282MHz,CDCl3)δ-134.79(dd,J＝11.0,8.3Hz,1F)。
实施例69:化合物55
根据通用方法B，用0.5mmol芳基硼酸新戊二醇酯55a投入反应得到55(172mg,产率：90％)。产物通过硅胶柱柱层析纯化(正己烷/二氯甲烷＝6:4到1:1)，产物为无色透明油状物。1H NMR(500MHz,CDCl3)δ7.32(d,J＝10.6Hz,1H),7.17(d,J＝8.3Hz,1H),6.97-6.91(m,3H),6.88-6.84(m,2H),6.59(t,J＝56.4Hz,1H),4.71(q,J＝6.7Hz,1H),4.21-4.12(m,2H),1.62(d,J＝6.7Hz,3H),1.61-1.59(m,2H),1.32(m,2H),0.90(t,J＝7.4Hz,3H)。19FNMR(376MHz,CDCl3)δ-109.86(d,J＝56.4Hz,2F),-130.90(dd,J＝10.0Hz,8.7Hz,1F)。13C NMR(125MHz,CDCl3)δ172.1,154.3,153.2(d,J＝250.1Hz),150.0,147.5(dt,J＝11.0,1.9Hz),129.7(td,J＝23.3,6.2Hz),121.9(td,J＝6.4,3.8Hz),120.0,119.4,116.4,114.4(dt,J＝20.2,5.9Hz),113.6(td,J＝239.0,1.6Hz),73.2,65.1,30.5,18.9,18.6,13.6。IR(薄膜法)vmax 2962,2935,2875,1752,1625,1502cm-1。MS(EI):m/z(％)382(M+),332,281,254,155,91(100)。HRMS:理论值:C20H21O4F3:382.1392；实测值:382.1399。
实施例70-87
向氩气无水无氧保护的25mL的Schlenk反瓶中依次加无水K2CO3(粉末,2.0-4.0eq.),对苯二酚(2.0eq.),Pd2(dba)3(2.5mol％),Xantphos(7.5mol％)和ArB(OH)2(0.3or 0.5mmol)。然后加入一个ClCF2H溶液和新蒸的1,4二氧六环(1.0mL,0.3mmol级反应或2.5mL,0.5mmol级反应)。塞上封管塞后将反应混合物加热至80-110度搅拌反应24小时。反应结束后浓缩柱层析即得目标产物。
实施例88-99
向氩气无水无氧保护的25mL的Schlenk反瓶中依次加无水K2CO3(粉末,2.0-4.0eq.),芳基酚(0-2.0eq.),Pd2(dba)3(2.5mol％),Xantphos(7.5mol％)和ArB(OH)2(0.3or 0.5mmol)。然后加入一个ClCF2H溶液和新蒸的1,4二氧六环(1.0mL,0.3mmol级反应或2.5mL,0.5mmol级反应)。塞上封管塞后将反应混合物加热至110度搅拌反应48小时。反应结束后浓缩柱层析即得目标产物。
实施例100-109
向氩气无水无氧保护的25mL的Schlenk反瓶中依次加无水K2CO3(粉末,2.0-4.0eq.),对苯二酚(2.0eq.),Pd2(dba)3(2.5mol％),Xantphos(7.5mol％)和芳基硼盐或硼酯(0.3or 0.5mmol)。然后加入ClCF2H溶液和新蒸的1,4二氧六环(1.0mL,0.3mmol级反应或2.5mL,0.5mmol级反应)。塞上封管塞后将反应混合物加热至110度搅拌反应48小时。反应结束后浓缩柱层析即得目标产物。
实施例110-113
向氩气无水无氧保护的25mL的Schlenk反瓶中依次加无水K2CO3(粉末,2.0-4.0eq.),对苯二酚(2.0eq.),Pd(II)(2.5mol％),Xantphos(7.5mol％)和芳基硼盐或硼酯(0.3or 0.5mmol)。然后加入ClCF2H溶液和新蒸的1,4二氧六环(1.0mL,0.3mmol级反应或2.5mL,0.5mmol级反应)。塞上封管塞后将反应混合物加热至110度搅拌反应48小时。反应结束后浓缩柱层析即得目标产物。
实施例114-117
向氩气无水无氧保护的25mL的Schlenk反瓶中依次加无水K2CO3(粉末,2.0-4.0eq.),对苯二酚(2.0eq.),Pd2(dba)3(2.5mol％),Xantphos(7.5mol％),氧化剂(0.05-1.0eq.)和芳基硼盐或硼酯(0.3or 0.5mmol)。然后加入ClCF2H溶液和新蒸的1,4二氧六环(1.0mL,0.3mmol级反应或2.5mL,0.5mmol级反应)。塞上封管塞后将反应混合物加热至110度搅拌反应48小时。反应结束后浓缩柱层析即得目标产物。
在本发明提及的所有文献都在本申请中引用作为参考，就如同每一篇文献被单独引用作为参考那样。此外应理解，在阅读了本发明的上述讲授内容之后，本领域技术人员可以对本发明作各种改动或修改，这些等价形式同样落于本申请所附权利要求书所限定的范围。

Claims (14)

1.一种如式C所示的α-芳基、杂芳基或烯基-α,α-二氟甲基类化合物的制备方法，其包含如下步骤：在溶剂中，在40℃-140℃下，在钯盐、碱和芳基酚类化合物存在的条件下，将式A化合物或式D化合物与式B化合物进行偶联反应，即可；
其中，所述的式D化合物为所述的式A化合物的金属复合物，M为碱金属；
R1、R2和R3各自独立地选自下组：氢、C1-10全氟烷基、C1-10烷基、C2-10烯基、C2-10炔基、C1-10酰胺基、C1-10羰基、氢甲酰基、卤素、取代或未取代的苯基、取代或未取代的吡啶基、取代或未取代的呋喃基、取代或未取代的噻吩基、取代或未取代的噻唑基、取代或未取代的吡咯基、C1-10烷氧基、-COOC1-10烷基、-C＝COOC1-10烷基、硝基、氰基、羟甲基、-S-C1-10烷基；或者，R1和/或R2、与R3以及相邻的双键共同构成：取代或未取代的苯基、取代或未取代的吡啶基、取代或未取代的呋喃基、取代或未取代的噻吩基、取代或未取代的噻唑基、取代或未取代的吡咯基、取代或未取代的萘基、取代或未取代的蒽基、取代或未取代的菲基、或取代或未取代的C6-20稠环芳基；
各个Z独立地选自下组：无、F、Cl、Br、S、O或N；
其中，所述的式A化合物中，
当各个Z独立地为无时，R4A和R4A’各自独立地选自C1-10烷基或C3-10环烷基；或者R4A和R4A’共同构成取代的或未取代的C1-10烷基、或取代的或未取代的C3-10环烷基；
当各个Z独立地选自F、Cl或Br时，R4A和R4A’为无；
当各个Z独立地选自S、O或N时，R4A和R4A’各自独立地选自氢、C1-10烷基、C3-10环烷基、苯基、C2-10烯基、C2-10炔基、或C1-10烷氧基；或者R4A和R4A’共同构成取代的或未取代的C1-10烷基、取代的或未取代的C3-10环烷基、或取代的或未取代的苯基；
其中，所述的式D化合物中，
当各个Z独立地为无时，R4D、R4D’和R4D”各自独立地选自：C1-10烷基、或C3-10环烷基；或者R4D、R4D’、R4D”中的两个基团共同构成取代的或未取代的C1-10烷基、或取代的或未取代的C3-10环烷基；或者R4D、R4D’、R4D”共同构成取代的或未取代的C1-10烷基、或取代的或未取代的C3-10环烷基；
当各个Z独立地选自F、Cl或Br时，R4D、R4D’和R4D”为无；
当各个Z独立地选自S、O或N时，R4D、R4D’和R4D”各自独立地选自：氢、C1-10烷基、C3-10环烷基、苯基、C2-10烯基、C2-10炔基、或C1-10烷氧基；或者R4D、R4D’和R4D”中的两个基团共同构成取代的或未取代的C1-10烷基、取代的或未取代的C3-10环烷基、或取代的或未取代的苯基；或者R4D、R4D’和R4D”共同构成取代的或未取代的C1-10烷基、或取代的或未取代的C3-10环烷基；
其中，所述的取代的是指基团中的一个或多个氢被选自下组的取代基所取代：C1-10全氟烷基、C1-10烷基或被一个或多个选自羟基或C1-10烷氧基的取代基所取代的C1-10烷基、C2-10烯基、C2-10炔基、C1-10酰胺基、苯并丁二酰亚胺基、C1-10羰基、氢甲酰基、卤素、未取代的苯基或被选自C1-10烷基、C2-10烯基、C2-10炔基、C1-10烷氧基中一个或多个取代基所取代的苯基、C1-10烷氧基、苄氧基、苯氧基、萘氧基、-COOC1-10烷基、-C＝CHCOOC1-10烷基、硝基、氰基、羟甲基、羟基、-S-C1-10烷基、C1-10烷基取代硅基、胺基或被一个或两个选自C1-10烷基或苯基的取代基所取代的胺基、或5元或6元的含氮杂环基。
2.如权利要求1所述的制备方法，其特征在于，其中，
所述的偶联反应的反应温度为60-120℃，优选80-110℃；
和/或，所述的溶剂为H2O、四氢呋喃、乙醚、二甲基乙二醚、1,4-二氧六环、甲苯、N-甲基吡咯烷酮、N,N-二甲基甲酰胺、二甲基亚砜、1,3-二甲基-3,4,5,6-四氢-2-嘧啶酮、甲基叔丁基醚和N,N-二甲基乙酰胺中的一种或多种；优选四氢呋喃、乙醚、二甲基乙二醚、1,4-二氧六环和甲苯中的一种或多种；
和/或，所述的式B化合物以其在有机溶剂中的溶液形式参与反应，优选以其二氧六环溶液参与反应；
和/或，所述的式A化合物与所述的溶剂的摩尔体积比为0.01-1mmol/mL；优选为0.2-0.5mmol/mL，进一步优选为0.3mmol/mL；
和/或，所述的式D化合物与所述的溶剂的摩尔体积比为0.01-1mmol/mL；优选为0.2-0.5mmol/mL，进一步优选为0.3mmol/mL；
和/或，所述的钯盐为二价钯催化剂和/或零价钯催化剂；所述的二价钯催化剂优选为Pd(OAc)2、Pd(acac)2、PdBr2、氯化烯丙基钯(II)二聚物、三氟乙酸钯、(1,5-环辛二烯)二氯化钯(II)、二(乙酰丙酮)钯(II)、[1,3-双二苯基磷丙烷]氯化钯、1,2-二(二苯基膦基)乙烷二氯化钯(II)、特戊酸钯、二氯二(三环己基瞵)钯、1,4-双(二苯基膦丁烷)二氯化钯、PdCl2(dppf)、PdCl2(PPh3)2、PdCl2(Xantphos)、[PdCl(C3H5)]2、PdCl2(MeCN)2、PdCl2(PhCN)2、 中的一种或多种；所述的零价钯催化剂优选为Pd2(dba)3、Pd(dba)2、Pd2(dba)3.CHCl3、Pd(PPh3)4、Pd(PCy3)2、Pd(COD)2和Pd/C中的一种或多种；
和/或，所述的钯盐与所述的式A化合物或式D化合物的摩尔比为0.01-0.1；优选为0.025-0.05；
和/或，所述的碱为碱金属氢氧化物、碱金属碳酸盐、碱金属碳酸氢盐、碱金属磷酸盐、碱金属有机酸盐、碱金属醇盐或有机胺中的一种或多种；其中，所述的金属氢氧化物优选氢氧化锂、氢氧化钠、氢氧化钾、氢氧化铷或氢氧化铯；所述的碱金属碳酸盐优选碳酸锂、碳酸钠、碳酸钾、碳酸铷或碳酸铯；所述的碱金属碳酸氢盐优选碳酸氢锂、碳酸氢钠、碳酸氢钾、碳酸氢铷或碳酸氢铯；所述的碱金属磷酸盐优选磷酸锂、磷酸钠、磷酸钾、磷酸铷或磷酸铯；所述的碱金属有机酸盐优选碱金属甲酸盐、碱金属丙酸盐、碱金属金刚酸盐、碱金属特戊酸盐或碱金属苯甲酸盐；所述的碱金属醇盐优选叔丁醇锂、叔丁醇钠、叔丁醇钾、叔丁醇镁或甲醇钠；所述的有机胺优选三乙胺或二异丙基乙基胺；
和/或，所述的碱与所述的式A化合物或式D化合物的摩尔比为1-4，优选2-3；
和/或，所述的芳基酚类化合物为各种取代或未取代的苯酚、邻苯二酚、对苯二酚中的一种或多种；其中，所述的取代为被一个或多个烷基、烷氧基或卤代烷基取代；优选为苯酚、对甲氧基苯酚、对三氟甲基苯酚、2,6-二甲基苯酚、2,6-二异丙基苯酚、邻苯二酚和对苯二酚中的一种或多种；
和/或，所述的芳基酚类化合物与所述的式A化合物或式D化合物的摩尔比为0.1-4；优选0.25-3，进一步优选1-2。
3.如权利要求1所述的制备方法，其特征在于，
所述的钯盐为PdQ2、PdLnCl2、Pd(PPh3)4、Pd2(dba)3.CHCl3、Pd2(dba)3或Pd(dba)2；其中，Q为醋酸根、三氟醋酸根或卤素；L选自三苯基膦、邻甲氧基三苯基膦、邻甲基三苯基膦、dppf、dppb、dppm、dppe和dppp中的一种或多种；0<n<3；优选所述的钯盐为Pd2(dba)3和/或Pd(PPh3)4。
4.如权利要求1所述的制备方法，其特征在于，
所述的偶联反应的反应体系中还包括配体；其中，所述的配体优选为如下式所述的膦配体中的一种或多种：
进一步优选三苯基膦、邻甲氧基三苯基膦、邻甲基三苯基膦、dppf、dppb、dppm、dppe和dppp中的一种或多种；所述的配体与所述的钯盐的摩尔比优选为1.5-3；
和/或，所述的偶联反应的反应体系中还包括氧化剂；其中，所述的氧化剂优选为碳酸银、三氯化铁和苯醌中的一种或多种。
5.如权利要求1所述的制备方法，其特征在于，其中，
R1为氢或不存在，R2与R3以及相邻的双键共同构成取代或未取代的苯基或取代或未取代的C6-20稠环芳基；所述的C6-20稠环芳基优选为C3-16环基稠合的苯基，所述的C3-16环基优选为C3-8环烷基、C3-8环杂烷基、C3-8环烯基、或C3-8杂芳基；
和/或，R1和R3各自独立地为取代或未取代的苯基；
和/或，所述的式A化合物中，当各个Z独立地选自S或O时，R4A和R4A’为氢，或者R4A和R4A’共同构成取代的或未取代的C1-10烷基、取代的或未取代的C3-10环烷基、或取代或未取代的苯基；其中，所述的取代的或未取代的C1-10烷基优选为取代的或未取代的C2-8烷基，进一步优选为-CH2-C(CH3)2-C(CH3)2-CH2-、-CH2-C(CH3)2-CH2-或-CH2-CH2-；所述的取代的或未取代的C3-10环烷基优选为取代的或未取代的C6-8环烷基，进一步优选为所述的取代或未取代的苯基优选为
和/或，所述的式D化合物为所述的式A化合物与MF的复合物，MF选自LiF、NaF、KF或CsF；
和/或，所述的式D化合物中，当各个Z独立地选自S或O时，R4D、R4D’和R4D”各自独立地选自：氢、C1-10烷基、苯基、C2-10烯基、C2-10炔基、或C1-10烷氧基；或者R4D、R4D’和R4D”中的两个基团共同构成取代的或未取代的C1-10烷基、或取代的或未取代的苯基；或者R4D、R4D’和R4D”共同构成取代的或未取代的C1-10烷基；
其中，所述的取代的是指基团中的一个或多个氢被选自下组的取代基所取代：C1-10全氟烷基、C1-10烷基或被一个或多个选自羟基或C1-10烷氧基的取代基所取代的C1-10烷基、C2-10烯基、C2-10炔基、C1-10酰胺基、苯并丁二酰亚胺基、C1-10羰基、氢甲酰基、卤素、未取代的苯基或被选自C1-10烷基、C2-10烯基、C2-10炔基、C1-10烷氧基中一个或多个取代基所取代的苯基、C1-10烷氧基、苄氧基、苯氧基、萘氧基、-COOC1-10烷基、-C＝CHCOOC1-10烷基、硝基、氰基、羟甲基、羟基、-S-C1-10烷基、C1-10烷基取代硅基、胺基或被一个或两个选自C1-10烷基或苯基的取代基所取代的胺基、或5元或6元的含氮杂环基。
6.如权利要求1或5所述的制备方法，其特征在于，所述的式A化合物选自下组：
上述各式中，Z、R4A和R4A’各自独立地如权利要求1或5所述；X为CH或N；Y为S、O或NR8，R8为氢、苯基、C1-10烷基、C2-10烯基、C2-10炔基、或C1-10烷氧基；
或，上述各式中一个或多个氢被选自下组的取代基所取代：C1-10全氟烷基、C1-10烷基或羟基取代的C1-10烷基、C2-10烯基、C2-10炔基、C1-10酰胺基、C1-10羰基、氢甲酰基、羟甲基、羟基、卤素、未取代的苯基或被选自C1-10烷基、C2-10烯基、C2-10炔基和C1-10烷氧基中一个或多个取代基所取代的苯基、C1-10烷氧基、苄氧基、苯氧基、萘氧基、-COOC1-10烷基、-C＝CHCOOC1-10烷基、硝基、氰基、-S-C1-10烷基、C1-10烷基取代的硅基、胺基或被一个或两个选自C1-10烷基或苯基的取代基所取代的胺基、或5元或6元的含氮杂环基。
7.如权利要求1或5所述的制备方法，其特征在于，所述的式A化合物选自下组：
上述各式中，Z、R4A和R4A’各自独立地如权利要求1或5所述。
8.如权利要求1或5所述的制备方法，其特征在于，所述的式A化合物选自下组：
9.如权利要求1或5所述的制备方法，其特征在于，所述的式D化合物选自下组：
上述各式中，X为CH或N；Y为S、O或NR8，R8为氢、苯基、C1-10烷基、C2-10烯基、C2-10炔基或C1-10烷氧基；
或，上述各式中一个或多个氢被选自下组的取代基所取代：C1-10全氟烷基、C1-10烷基或羟基取代的C1-10烷基、C2-10烯基、C2-10炔基、C1-10酰胺基、C1-10羰基、氢甲酰基、羟甲基、羟基、卤素、未取代的苯基或被选自C1-10烷基、C2-10烯基、C2-10炔基、C1-10烷氧基中一个或多个取代基所取代的苯基、C1-10烷氧基、苄氧基、苯氧基、萘氧基、-COOC1-10烷基、-C＝CHCOOC1-10烷基、硝基、氰基、-S-C1-10烷基、C1-10烷基取代的硅基、胺基或被一个或两个选自C1-10烷基或苯基的取代基所取代的胺基、5元或6元的含氮杂环基。
10.如权利要求1或5所述的制备方法，其特征在于，所述的式D化合物选自下组：
11.式C化合物，其结构如权利要求1-10任一项所述。
12.式C化合物，其选自下组：
或，上述各式中一个或多个氢被选自下组的取代基所取代：C1-10全氟烷基、C1-10烷基或羟基取代的C1-10烷基、C2-10烯基、C2-10炔基、C1-10酰胺基、C1-10羰基、氢甲酰基、羟甲基、羟基、卤素、未取代的苯基或被选自C1-10烷基、C2-10烯基、C2-10炔基、C1-10烷氧基中一个或多个取代基所取代的苯基、C1-10烷氧基、苄氧基、苯氧基、萘氧基、-COOC1-10烷基、-C＝CHCOOC1-10烷基、硝基、氰基、-S-C1-10烷基、C1-10烷基取代的硅基、胺基或被一个或两个选自C1-10烷基或苯基的取代基所取代的胺基、或5元或6元的含氮杂环基。
13.式A化合物，其结构如权利要求1、5-8中任一项所述。
14.式D化合物，其结构如权利要求1、5、9和10中任一项所述。
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