CN107216307A - 一种高效合成1,1‑二芳基烷烃类化合物的方法 - Google Patents

一种高效合成1,1‑二芳基烷烃类化合物的方法 Download PDF

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CN107216307A
CN107216307A CN201710386236.7A CN201710386236A CN107216307A CN 107216307 A CN107216307 A CN 107216307A CN 201710386236 A CN201710386236 A CN 201710386236A CN 107216307 A CN107216307 A CN 107216307A
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刘国生
张文
陈品红
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Abstract

本发明公开了一种高效合成1,1‑二芳基烷烃类化合物的方法。所述方法包括以下步骤：在气体保护下，在铜催化剂、双氮配体、碱和氧化剂的作用下，式I化合物和式II化合物在有机溶剂中进行如下反应，从而得到式III化合物。本发明的方法具有反应条件温和、操作简单、底物适应性广、官能团兼容性高等优点，具有较高的学术和应用价值。

Description

一种高效合成1,1-二芳基烷烃类化合物的方法
技术领域
本发明属于有机化学领域，具体地，涉及一种高效合成1,1-二芳基烷烃类化合物的方法。
背景技术
1,1-二芳基烷烃骨架分子广泛存在于天然产物和药物分子中，因此发展高效合成这类骨架分子的方法具有重要意义。[(a)McNally,D.J.；Wurms,K. V.；Labbe,C.；Quideau,S.；Belanger,R.R.J.Nat.Prod.2003,66,1280.(b)Liang, H.；Wu,X.；Yalowich,J.C.；Hasinoff,B.B.Mol.Pharmacol.2008,73,686.(c) Hu,Q.Z.；Yin,L.N.；Jagusch,C.；Hille,U.E.；Hartmann,R.W.J.Med.Chem. 2010,53,5049.]。合成这类骨架分子的传统方法很多，例如，1,1-二芳基烯烃的氢化反应；Rh催化活性烯烃的共轭加成反应；过渡金属催化烯烃的双官能化反应；以及过渡金属催化苄基亲核或亲电试剂与芳基试剂的偶联反应等 [(a)Wang,Z.；Ai,F.；Wang,Z.；Zhao,W.；Zhu,G.；Lin,Z.；Sun,J.J.Am.Chem. Soc.2015,137,383.(b)Paquin,J.F.；Defieber,C.；Stephenson,C.R.J.；Carreira,E.M.J.Am.Chem.Soc.2005,127,10850.(c)Friis,S.D.；Pirnot,M.T.；Buchwald,S.L.J.Am.Chem.Soc.2016,138,8372.(d)Do,H.-Q.；Chandrashekar,E.R.R.； Fu,G.C.J.Am.Chem.Soc.2013,135,16288.]。然而，这些反应过程中不可避免地需要预先制备官能化的底物。因此，从原子经济性和合成步骤的高效性角度来看，苄位C-H键的直接芳基化反应是理想的合成1,1-二芳基烷烃类化合物的方法。
过去十几年里，导向过渡金属催化C-H键的芳基化反应虽然得到长足的发展，但是这些反应中不可避免需要引入导向官能团，这在一定程度上限制了底物的范围[Wasa,M.；Chan,K.S.L.；Zhang,X.-G.；He,J.；Miura,M.；Yu,J.- Q.J.Am.Chem.Soc.2012,134,18570.]。相比之下自由基参与的C-H键的直接芳基化反应发展的更为缓慢。
最近，光与镍共催化的方法使得杂原子邻位C-H键的直接芳基化反应得以实现，此类反应使用芳基卤化物作为芳基源[(a)Shaw,M.H.；Shurtleff,V.W. Terrett,J.A.；Cuthbertson,J.D.；MacMillan,D.W.C.Science 2016,352,1304. (b)Heitz,D.R.；Tellis,J.C.；Molander,G.A.J.Am.Chem.Soc.2016,138,12715. (c)Shields,B.J.；Doyle,A.G.J.Am.Chem.Soc.2016,138,12719.]。然而这类反应中通常需要含杂原子的底物大大过量或者直接作为溶剂参与反应，显然这些反应使得复杂底物的后期修饰更加困难。
因此，本领域急需一种能实现苄位C-H键芳基化反应的高效、简单的反应方法。
发明内容
本发明所要解决的技术问题是为了克服现有技术中反应底物需要引入导向官能团及底物普适性窄、官能团选择范围小等缺点，因而提供了一种高效合成1,1-二芳基烷烃类化合物的方法。本发明的方法具有反应条件温和、操作简单、底物普适性高、官能团兼容性好等特点。
本发明主要是通过以下技术方案解决上述技术问题的。
本发明提供了一种合成如式Ⅲ所示的1，1-二芳基取代烷烃类化合物的方法，所述方法包括以下步骤：
在气体保护下，在铜催化剂、双氮配体、碱和氧化剂的作用下，式I 化合物和式II化合物在有机溶剂中进行如下反应，从而得到式III化合物；
其中，
Ar1为取代或未取代的C6-C14芳基、或取代或未取代的C2-C14杂芳基,或者Ar1与R形成如下成环结构： 其中，
每个R1相同或不同，各自独立地选自氢、C1-C6烷基、卤素、-OR2、- CO2R3、苯基、C2-C4酯基、氰基和对甲基苯磺酰基中的一个或多个，R2选自 C1-C4烷基或C1-C4酰基，R3选自C1-C4烷基；当取代基为多个时，所述的取代基相同或不同；
所述取代的C6-C14芳基和取代的C2-C14杂芳基中的取代基各自独立地选自卤素、氰基、C1-C4醛基、C1-C4烷基、C1-C4烷氧基、C1-C4卤代烷基、 C1-C4卤代烷氧基、C6-C10芳基、C2-C6杂芳基、和-OR2’中的一个或多个，或者所述取代的C6-C14芳基和取代的C2-C14杂芳基中的取代基与其母核形成如下结构：其中R1’为C1-C4烷基,R2’为C6-C10芳基；每个R1相同或不同，各自独立地选自氢、C1-C6烷基、卤素、 -OR2、-CO2R3、苯基、C2-C4酯基、氰基和对甲基苯磺酰基中的一个或多个， R2选自C1-C4烷基或C1-C4酰基，R3选自C1-C4烷基；R4选自C1-C4烷基或- SO2Ph；当取代基为多个时，所述的取代基相同或不同；
所述取代或未取代的C2-C14杂芳基和所述C2-C6杂芳基中的杂原子各自独立地选自O、N和S中的一个或多个，杂原子的个数为1-3个，当杂原子为多个时，所述的杂原子相同或不同；
Ar2为取代或未取代的C6-C14芳基、或取代或未取代的C2-C14杂芳基,所述取代的C6-C14芳基和所述取代的C2-C14杂芳基中的取代基各自独立地选自卤素、氰基、C1-C4醛基、C1-C4烷基、C1-C4烷氧基、C1-C4卤代烷基、C1- C4卤代烷氧基、和-SO2R3’中的一个或多个，其中R1’和R3’各自独立地为C1-C4烷基,当取代基为多个时，所述的取代基相同或不同；所述取代或未取代的C2-C10杂芳基中的杂原子选自O、N和S中的一个或多个，杂原子的个数为1-3个，当杂原子为多个时，所述的杂原子相同或不同；
R选自取代或未取代的C1-C20直链或支链烷基、取代或未取代的C6-C10芳基、或取代或未取代的C2-C10杂芳基；所述取代的C1-C20直链或支链烷基的取代基选自-N3、卤素、C6-C10芳基、-OR5和-CO2R5中的一个或多个，其中每个R5相同或不同，各自独立为C1-C6烷基；所述取代的C6-C10芳基中的取代基选自以下任意一个或多个基团：C1-C4烷氧基和-R6Ph，其中R6为C1- C4烷基；所述取代的C2-C10杂芳基的取代基为卤素取代的C6-C10芳基；当取代基为多个时，所述的取代基相同或不同；所述取代或未取代的C2-C10杂芳基中的杂原子选自O、N和S中的一个或多个，杂原子的个数为1-3个，当杂原子为多个时，所述的杂原子相同或不同。
所述的合成如式Ⅲ所示的1，1-二芳基取代烷烃类化合物的方法，其中，
Ar1为取代或未取代的C6-C10芳基、或取代或未取代的C2-C10杂芳基，所述取代的C6-C10芳基和取代的C2-C10杂芳基中的取代基各自独立地选自 F、Cl、Br、I、氰基、C1-C4醛基、甲基、乙基、正丙基、异丙基、正丁基、叔丁基、异丁基、三氟甲基、三氟甲氧基、甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、异丁氧基、叔丁氧基、苯基、-OPh、-SO2Ph、 中的一个或多个，其中R9选自C1-C4烷基或C1-C4酰基；当取代基为多个时，所述的取代基相同或不同；
优选的Ar1选自 其中每个R1相同或不同，各自独立地选自氢、C1-C6烷基、卤素、-OR2、-CO2R3、苯基、C2-C4酯基、氰基和对甲基苯磺酰基中的一个或多个，R2选自C1-C4烷基或C1-C4酰基，R3选自C1-C4烷基；R7与R8各自独立地选自氢或C1-C6烷基、或者R7与R8形成3-7元碳环；R9选自C1- C4烷基或C1-C4酰基；X1、X2和X3各自独立地选自O、S或N；当取代基为多个时，所述的取代基相同或不同；
R选自取代或未取代的C1-C16直链或支链烷基、取代或未取代的C6-C10芳基、或取代或未取代的C2-C8杂芳基；所述取代的C1-C16直链或支链烷基的取代基选自-N3、F、Cl、Br、I、苯基、溴乙基、甲氧基、乙氧基、 中的一个或多个；所述取代的C6-C10芳基的取代基选自甲氧基、乙氧基或苯乙基；所述取代的C2-C8杂芳基的取代基为氟代苯基；当取代基为多个时，所述的取代基相同或不同；所述取代或未取代的C2-C8杂芳基中的杂原子选自O、N和S中的一个或多个，杂原子的个数为1-3个，当杂原子为多个时，所述的杂原子相同或不同；
优选的R为甲基、-CH2N3、苯基、苯甲基、正庚基、异丙基、异丁基、 -C3H6Br、-CH2OCH3、-CH2OAc、-CH2CO2CH3、 -Ph-CH2-CH2-Ph或-PhOEt；
所述Ar1与R形成的成环结构优选为
Ar2为取代或未取代的C6-C10芳基、或取代或未取代的C2-C8杂芳基，所述取代的C6-C10芳基和取代的C2-C8杂芳基的取代基各自独立地选自F、Cl、 Br、I、甲基、乙基、正丙基、异丙基、正丁基、叔丁基、异丁基、-SO2CH3、氰基、C1-C4醛基、三氟甲基、三氟甲氧基、乙酰氧基、甲氧基和乙氧基中的一个或多个；当取代基为多个时，所述的取代基相同或不同；
优选的Ar2为其中每个R10相同或不同，各自独立地选自氢、F、Cl、Br、I、甲基、乙基、正丙基、异丙基、正丁基、叔丁基、异丁基、-SO2CH3、氰基、C1-C4醛基、三氟甲基、三氟甲氧基、乙酰氧基、甲氧基和中的一个或多个；X4选自O、S或 N；当取代基为多个时，所述的取代基相同或不同。
所述的合成如式Ⅲ所示的1，1-二芳基取代烷烃类化合物的方法，其中，所述的铜催化剂选自铜粉、碘化亚铜、氯化亚铜、溴化亚铜、氧化亚铜、醋酸亚铜、三氟甲磺酸亚铜和苯的2:1摩尔比复合物、噻吩甲酸亚铜、溴化亚铜的二甲硫醚复合物、四乙腈六氟磷酸铜、四乙腈三氟甲磺酸铜、四乙腈四氟硼酸铜、氯化铜、溴化铜、氟化铜、醋酸铜和三氟甲磺酸铜中的一种或多种，优选为碘化亚铜、四乙腈四氟硼酸铜、三氟甲磺酸铜和醋酸亚铜中的一种或多种，更优选为醋酸亚铜。
所述的合成如式Ⅲ所示的1，1-二芳基取代烷烃类化合物的方法，其中，所述的双氮配体选自：
其中R8’、R9’、R10’、R11’各自独立地选自氢、卤素、C2-C4酯基、氰基、C1-C6烷基和C6-C10芳基中的一个或多个，当取代基为多个时，所述的取代基相同或不同；优选为更优选为
所述的合成如式Ⅲ所示的1，1-二芳基取代烷烃类化合物的方法，
其中，所述的气体为氮气或氩气；
其中，所述的氧化剂为N-氟代双苯磺酰胺(NFSI)；
其中，所述的碱选自碳酸锂、碳酸钠、碳酸钾、碳酸镁、碳酸钡、碳酸钙、碳酸铷、碳酸铯、碳酸银、碳酸铵、碳酸氢钠、碳酸氢钾、碳酸氢铵、磷酸钾、磷酸锂、氟化锂、氟化钠、氟化钾、氟化铯、氟化银、叔丁醇锂、叔丁醇钠、叔丁醇钾、甲醇锂、甲醇钠、乙醇钠、氢氧化钠、氢氧化钾、氢化钠、氢化钾、乙酸钠、乙酸钾、三乙胺、二异丙基乙基胺和三乙烯二胺中的一种或多种，优选碳酸锂、碳酸钠、碳酸钾、碳酸镁、碳酸铷、碳酸铯、碳酸铵、碳酸氢钠和碳酸氢钾中的一种或多种，更优选碳酸锂；
其中，所述的有机溶剂为正己烷、乙腈、苯、氯苯、溴苯、氟苯、三氟甲苯、六氟苯、二氯甲烷、二氯乙烷、三氯甲烷、四氯化碳、1,1,2,2-四氯乙烷、丙酮、乙醚、四氢呋喃、乙二醇二甲醚、叔丁基甲基醚、1,4-二氧六环、甲醇、乙醇、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、N-甲基吡咯烷酮、六甲基磷酰胺和二甲亚砜中的一种或多种，优选苯和N,N-二甲基乙酰胺混合溶剂，混合比例为体积比9:1-1:9，优选的混合比例为体积比4:1。
所述的合成如式Ⅲ所示的1，1-二芳基取代烷烃类化合物的方法，
其中，所述的铜催化剂，用量为式I化合物的1-50％摩尔当量，优选5％- 30％摩尔当量，更优选10％摩尔当量；
其中，所述的双氮配体，用量为式I化合物的1-60％摩尔当量，优选5％- 30％摩尔当量，更优选12％摩尔当量；
其中，所述的式Ⅱ化合物，用量为式I化合物的100-500％摩尔当量，优选200-300％摩尔当量，更优选200％摩尔当量；
其中，所述的氧化剂，用量为式I化合物的100-400％摩尔当量，优选 250-300％摩尔当量；
其中，所述的碱，用量为式I化合物的50-300％摩尔当量，优选200％摩尔当量。
所述的合成如式Ⅲ所示的1，1-二芳基取代烷烃类化合物的方法，其中，所述的铜催化剂与双氮配体的摩尔比为2:1-1:3，优选1:1.2。
所述的合成如式Ⅲ所示的1，1-二芳基取代烷烃类化合物的方法，其中，所述的式I化合物、氧化剂和式II化合物的摩尔比为1:1:1-1:4:5，优选 1:2.5:2—1:3:3。
所述的合成如式Ⅲ所示的1，1-二芳基取代烷烃类化合物的方法，其中，所述的式I化合物的浓度为0.01-1.0摩尔/升，优选0.1-0.2摩尔/升。
所述的合成如式Ⅲ所示的1，1-二芳基取代烷烃类化合物的方法，
其中，所述反应温度为0-80℃，优选20-30℃；
其中，所述反应时间为4-24小时。
所述的合成如式Ⅲ所示的1，1-二芳基取代烷烃类化合物的方法，其中，所述反应在搅拌下进行。
所述的合成如式Ⅲ所示的1，1-二芳基取代烷烃类化合物的方法，其中，所述搅拌速度为100-1500转/分钟。
在本发明一优选实施例中，所述C2-C4酯基的结构为-CO2-RX,其中RX选自甲基、乙基、正丙基或异丙基。
在本发明一优选实施例中，在气体保护下，将铜催化剂、双氮配体和碱在有机溶剂中混合并搅拌，然后再加入氧化剂、式I化合物和式II化合物进行反应，从而得到式III化合物。
在本发明一优选实施例中，通过常规后处理来纯化所得产物。所述的常规后处理包括如下步骤：反应液用乙酸乙酯稀释，水洗；有机相经无水硫酸镁干燥后，过滤；滤液经浓缩后的残留物可以通过薄层层析、柱层析、重结晶、常压和减压蒸馏进一步纯化。
在本发明一优选实施例中，式I化合物选自如下任一化合物：
在本发明一优选实施例中，式Ⅱ化合物选自如下任一化合物：
在本发明一优选实施例中，式Ⅲ化合物选自如下任一化合物：
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：
本发明提供了一种有效的利用N-氟代双苯磺酰胺(NFSI)作为氧化剂，在铜催化剂、双氮配体和碱的协助下，通过苄位C-H键的芳基化反应，高效合成1,1-二芳基取代的烷烃的方法。与现有方法相比，本发明的技术方案反应条件温和、操作简单、官能团容忍性好，可适用于多种不同类型的芳基取代烷烃和芳基硼酸反应，也可用于复杂药物分子衍生物的后期修饰。
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。
实施例1
通用操作步骤1：在10mL反应管内，双氮配体(5.8mg,0.024mmol,12 mol％)、碳酸锂(29.6mg,0.4mmol,2equiv)和CuOAc(2.4mg,0.02mmol,10 mol％)在氩气保护下，溶解于Benzene/DMA(4:1,2mL)中，搅拌，反应液成棕褐色。0.5小时后，依次向反应管内加入NFSI(0.50mmol,2.5equiv)，式Ⅱ化合物(0.40mmol,2.0equiv)和式I化合物(0.20mmol,1.0equiv)。反应溶液由棕褐色变成蓝色。搅拌4-24小时。反应结束后，减压除去体系中的溶剂苯，残留物用20mL乙酸乙酯稀释，水洗(10mL×3)。有机相经无水MgSO4干燥，过滤，滤液经浓缩后，快速柱层析分离(石油醚/乙酸乙酯)得到目标产物。
通用操作步骤2：在10mL反应管内，双氮配体(5.8mg,0.024mmol,12 mol％)、碳酸锂(29.6mg,0.4mmol,2equiv)和CuOAc(2.4mg,0.02mmol,10 mol％)在氩气保护下，溶解于Benzene/DMA(4:1,1mL)中，搅拌，反应液成棕褐色。0.5小时后，依次向反应管内加入NFSI(0.60mmol,3.0equiv),式Ⅱ化合物(0.60mmol,3.0equiv)和式I化合物(0.20mmol,1.0equiv)。反应溶液由棕褐色变成蓝色。搅拌4-24小时。反应结束后，减压除去体系中的溶剂苯，残留物用20mL乙酸乙酯稀释，水洗(10mL×3)。有机相经无水MgSO4干燥，过滤，滤液经浓缩后，快速柱层析分离(石油醚/乙酸乙酯)得到目标产物。
化合物P1：
该反应按照通用操作步骤1进行，反应2.5小时后通过外加NFSI(1.25equiv) 和苯硼酸(1.0equiv)，进一步反应8小时。柱层析分离(石油醚：乙酸乙酯＝200:0-200:1)得到白色固体产物35.8mg，收率77％。
1H NMR(400MHz,CDCl3)δ8.12–8.05(m,1H),7.92–7.86(m,1H),7.79(d,J ＝8.0Hz,1H),7.55–7.44(m,4H),7.32–7.27(m,4H),7.24–7.18(m,1H),4.98 (q,J＝7.2Hz,1H),1.82(d,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ146.6, 141.5,133.9,131.7,128.7,128.4,127.6,126.9,125.9,125.8,125.4,125.3,124.3, 123.9,40.5,22.5.HRMS(EI)calculatedfor[M]+(C18H16)m/z 232.1252,found m/z 232.1244.
化合物P2：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝40:0- 20:1)得到白色固体产物34.4mg，收率59％。
1H NMR(400MHz,CDCl3)δ8.07–8.00(m,1H),7.90–7.84(m,1H),7.76(d,J ＝8.0Hz,1H),7.51–7.41(m,4H),7.28–7.22(m,2H),7.02–6.96(m,2H),4.94 (q,J＝7.2Hz,1H),2.27(s,3H),1.77(d,J＝7.2Hz,3H).13C NMR(100MHz, CDCl3)δ169.5,148.7,144.0,141.2,133.9,131.5,128.8,128.5,127.0,125.9, 125.4,125.3,124.3,123.8,121.3,39.9,22.5,21.1.HRMS(DART)calculated for [M+NH4]+(C20H22O2N)m/z 308.1645,found m/z308.1642.
化合物P3：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝400:0- 400:1)得到无色液体产物40.6mg，收率65％。
1H NMR(400MHz,CDCl3)δ8.02–7.97(m,1H),7.90–7.85(m,1H),7.78(d,J ＝8.0Hz,1H),7.52–7.42(m,4H),7.41–7.36(m,2H),7.14–7.09(m,2H),4.89 (q,J＝7.2Hz,1H),1.76(d,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ145.7, 140.8,134.0,131.5,129.3,128.8,127.2,126.0,125.4,124.3,123.8,119.7,40.0, 22.4.
化合物P4：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝20:0- 10:1)得到无色液体产物45.0mg，收率82％。
1H NMR(400MHz,CDCl3)δ8.00–7.95(m,1H),7.90–7.84(m,3H),7.79(d,J ＝8.0Hz,1H),7.53–7.48(m,1H),7.47–7.40(m,3H),7.33(d,J＝8.4Hz,2H), 4.98(q,J＝7.2Hz,1H),2.55(s,3H),1.80(d,J＝7.2Hz,3H).13C NMR(100 MHz,CDCl3)δ197.7,152.4,140.4,135.1,134.0,131.5,128.8,128.6,127.7,127.3, 126.0,125.42,125.38,124.3,123.7,40.6,26.5,22.2.HRMS(EI)calculated for [M]+(C20H18O)m/z 274.1358,found m/z 274.1365.
化合物P5：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝20:0- 10:1)得到白色固体产物49.7mg，收率96％。与此同时，该反应可以按照通用操作步骤1等比例放大至6mmol规模，得到白色固体产物1.38g，收率 89％。
1H NMR(400MHz,CDCl3)δ7.96–7.85(m,2H),7.81(d,J＝8.0Hz,1H),7.57 –7.49(m,3H),7.48–7.42(m,3H),7.33(d,J＝8.0Hz,2H),4.97(q,J＝7.2Hz, 1H),1.79(d,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ152.2,139.7,133.9, 132.3,131.3,128.9,128.3,127.5,126.1,125.5,125.4,124.4,123.4,118.9,109.8, 40.7,22.0.HRMS(EI)calculated for[M]+(C19H15N)m/z 257.1204,found m/z 257.1210.
化合物P6：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝30:0- 15:1)得到无色液体产物42.4mg，收率82％。
1H NMR(400MHz,CDCl3)δ9.94(s,1H),7.99–7.94(m,1H),7.90–7.85(m, 1H),7.82–7.75(m,3H),7.51(t,J＝7.6Hz,1H),7.49–7.43(m,3H),7.40(d,J ＝8.0Hz,2H),4.99(q,J＝7.2Hz,1H),1.81(d,J＝7.2Hz,3H).13C NMR(100 MHz,CDCl3)δ191.9,154.0,140.1,134.5,134.0,131.4,130.0,128.9,1282,127.4, 126.0,125.5,125.4,124.4,123.6,40.8,22.2.HRMS(EI)calculated for[M]+ (C19H16O)m/z 260.1201,found m/z 260.1196.
化合物P7：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝50:0- 30:1)得到无色液体产物47.2mg，收率81％。
1H NMR(400MHz,CDCl3)δ8.00–7.94(m,3H),7.89–7.85(m,1H),7.79(d,J ＝8.4Hz,1H),7.50(t,J＝7.6Hz,1H),7.47–7.40(m,3H),7.32(d,J＝8.4Hz, 2H),4.98(q,J＝7.2Hz,1H),3.89(s,3H),1.80(d,J＝7.2Hz,3H).13C NMR(100 MHz,CDCl3)δ167.0,152.1,140.5,134.0,131.5,129.8,128.8,127.9,127.6,127.3, 126.0,125.41,125.38,124.4,123.7,51.9,40.7,22.2.HRMS(DART)calculated for[M+H]+(C20H19O2)m/z 291.1380,found m/z291.1377.
化合物P8：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝400:0- 400:1)得到无色液体产物57.9mg，收率92％。
1H NMR(400MHz,CDCl3)δ8.02–7.94(m,1H),7.90–7.84(m,1H),7.78(d,J ＝8.0Hz,1H),7.50–7.40(m,4H),7.25(d,J＝8.8Hz,2H),7.10(d,J＝8.4Hz, 2H),4.94(q,J＝7.2Hz,1H),1.77(d,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3) δ147.3(d,J＝1.5Hz),145.3,140.8,134.0,131.5,128.9,128.8,127.3,126.0, 125.4,124.3,123.7,120.9,120.5(q,J＝255.0Hz),119.8,39.9,22.5.19F NMR (376MHz,CDCl3)δ-57.87(s).HRMS(DART)calculatedfor[M+NH4]+ (C19H19ONF3)m/z 334.1413,found m/z 334.1410.
化合物P9：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝8:1-4:1) 得到白色固体产物59.0mg，收率95％。
1H NMR(400MHz,CDCl3)δ7.91(d,J＝8.4Hz,1H),7.84–7.85(m,1H),7.81 (t,J＝8.0Hz,3H),7.50(t,J＝7.6Hz,1H),7.48–7.40(m,5H),5.00(q,J＝7.2 Hz,1H),3.01(s,3H),1.79(d,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ 153.2,139.7,138.0,133.9,131.3,128.9,128.4,127.6,127.2,126.1,125.5,125.4, 124.4,123.5,44.4,40.5(d,J＝5.3Hz),22.2.HRMS(DART)calculated for [M+H]+(C19H19O2S)m/z 311.1100,found m/z 311.1097.
化合物P10：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝8:1-4:1) 得到无色液体产物47.7mg，收率95％。
1H NMR(400MHz,CDCl3)δ8.06–8.00(m,1H),7.92–7.87(m,1H),7.80(d,J ＝8.0Hz,1H),7.54–7.44(m,4H),7.24(td,J＝7.6,5.6Hz,1H),7.06(d,J＝8.0 Hz,1H),6.96(dt,J＝6.4,2.4Hz,1H),6.89(td,J＝8.4,2.4Hz,1H),4.95(q,J＝ 7.2Hz,1H),1.79(d,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ163.0(d,J＝ 244.4Hz),149.4(d,J＝6.8Hz),140.7,134.0,131.5,129.8(d,J＝8.4Hz),128.8, 127.2,126.0,125.40(d,J＝1.5Hz),124.3,123.7,123.3(d,J＝3.1Hz),114.5(d, J＝21.3Hz),112.9(d,J＝20.5Hz),40.3,22.4.19F NMR(376MHz,CDCl3)δ- 113.26(m).HRMS(EI)calculated for[M]+(C18H15F)m/z 250.1158,found m/z 250.1151.
化合物P11：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝400:0- 400:1)得到无色液体产物46.5mg，收率87％。
1H NMR(400MHz,CDCl3)δ8.01–7.97(m,1H),7.89–7.84(m,1H),7.77(d,J ＝8.0Hz,1H),7.51–7.41(m,4H),7.23(t,J＝2.0Hz,1H),7.21–7.08(m,3H), 4.90(q,J＝7.2Hz,1H),1.76(d,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ 148.8,140.6,134.2,134.0,131.5,129.7,128.8,127.7,127.3,126.2,126.0,125.8, 125.4,124.3,123.7,40.3,22.4.HRMS(EI)calculated for[M]+(C18H15Cl)m/z 266.0862,found m/z 266.0860.
化合物P12：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝30:1- 15:1)得到无色液体产物46.5mg，收率87％。
1H NMR(400MHz,CDCl3)δ8.06–8.00(m,1H),7.90–7.81(m,2H),7.77(dd, J＝6.4,2.4Hz,1H),7.53–7.46(m,2H),7.45–7.40(m,2H),7.30–7.20(m,2H), 7.32(t,J＝7.6Hz,1H),5.93(q,J＝7.2Hz,1H),4.40–4.27(m,2H),1.76(d,J＝ 7.2Hz,3H),1.33(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ168.4,147.6, 141.4,133.9,131.8,131.7,130.1,129.9,128.5,128.0,127.0,125.9,125.8,125.3, 125.2,124.3,124.2,61.0,36.4,22.3,14.1.HRMS(EI)calculated for[M]+ (C21H20O2)m/z 304.1463,found m/z 304.1461.
化合物P13：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝300:0- 300:1)得到无色液体产物53.4mg，收率89％。
1H NMR(400MHz,CDCl3)δ8.00–7.93(m,1H),7.91–7.85(m,1H),7.80(d,J ＝8.0Hz,1H),7.53–7.40(m,4H),7.34(d,J＝2.0Hz,1H),7.32(d,J＝8.4Hz, 1H),7.05(dd,J＝8.4,J＝2.0Hz,1H),4.88(q,J＝7.2Hz,1H),1.76(d,J＝7.2 Hz,3H).13C NMR(100MHz,CDCl3)δ147.0,140.1,134.0,132.4,131.4,130.3, 129.9,129.5,128.9,127.5,127.1,126.1,125.5,125.4,124.3,123.5,39.9,22.3. HRMS(EI)calculated for[M]+(C18H14Cl2)m/z300.0473,found m/z 300.0469. 化合物P14：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝300:0- 300:1)得到无色液体产物54.4mg，收率95％。
1H NMR(400MHz,CDCl3)δ8.00–7.93(m,1H),7.91–7.84(m,1H),7.83–7.76 (m,1H),7.55–7.43(m,4H),7.12(d,J＝6.8Hz,1H),6.98–6.86(m,2H),5.22(q, J＝7.2Hz,1H),1.75(d,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ159.8(d, J＝247.6Hz),139.6,133.9,132.4,132.2(d,J＝4.7Hz),131.3,129.4(d,J＝4.7 Hz),128.8,127.4,126.2,125.5,125.3,124.5(d,J＝2.8Hz),124.0,123.4,116.0 (d,J＝25.6Hz),32.7(d,J＝2.8Hz),21.0.19FNMR(376MHz,CDCl3)δ-116.31 (t,J＝9.4Hz).HRMS(EI)calculated for[M]+(C18H14FCl)m/z284.0768,found m/z 284.0764.
化合物P15：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝80:1-40:1) 得到无色液体产物51.2mg，收率89％。
1H NMR(400MHz,CDCl3)δ7.95–7.87(m,2H),7.82(d,J＝8.0Hz,1H),7.53 –7.45(m,3H),7.43(d,J＝7.2Hz,1H),6.89–6.80(m,2H),4.86(q,J＝7.2Hz, 1H),1.75(d,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ151.1(ddd,J＝247.5, 9.2,3.8Hz),143.1(td,J＝6.1,3.8Hz),139.6,138.0(dt,J＝248.3,15.1Hz),134.0, 131.3,129.0,127.7,126.2,125.6,125.4,124.3,123.4,111.4(dd,J＝15.1,5.3Hz), 40.0,22.2.19F NMR(376MHz,CDCl3)δ-134.55(m),-163.96(m).HRMS(EI) calculated for[M]+(C18H13F3)m/z 286.0969,found m/z 286.0964.
化合物P16：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝40:1-20:1) 得到白色固体产物34.7mg，收率65％。
1H NMR(400MHz,CDCl3)δ8.21(dd,J＝4.8,1.6Hz,1H),7.89–7.83(m,2H), 7.80(d,J＝7.6Hz,1H),7.53-7.41(m,4H),7.26(dd,J＝8.0,2.0Hz,1H),7.00(dd, J＝7.6,4.4Hz,1H),5.27(q,J＝7.2Hz,1H),1.74(d,J＝7.2Hz,3H).13C NMR (100MHz,CDCl3)δ150.5,147.3,140.9,139.1,137.1,133.9,131.4,128.8,127.7, 126.4,125.6,125.2,124.0,123.5,122.9,37.1,20.2.HRMS(EI)calculated for [M]+(C17H14NCl)m/z 267.0815,foundm/z 267.0823.
化合物P17：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝20:1-10:1) 得到无色液体产物46.8mg，收率76％。
1H NMR(400MHz,CDCl3)δ8.37(d,J＝2.4Hz,1H),7.95–7.89(m,1H),7.89 –7.85(m,1H),7.79(d,J＝8.4Hz,1H),7.51–7.43(m,3H),7.41(d,J＝7.2Hz, 1H),7.33–7.30(m,1H),7.29–7.25(m,1H),4.91(q,J＝7.2Hz,1H),1.77(d,J ＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ149.6,141.3,139.6,139.3,137.7, 134.0,131.1,129.0,127.8,127.7,126.3,125.6,125.4,124.3,123.3,37.5,22.1. HRMS(EI)calculated for[M]+(C17H14NBr)m/z 311.0310,found m/z 311.0315.
化合物P18：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝8:1-4:1) 得到无色液体产物40.3mg，收率76％。
1H NMR(400MHz,CDCl3)δ8.37(s,2H),7.97–7.91(m,1H),7.89–7.85(m, 1H),7.78(d,J＝8.4Hz,1H),7.50–7.44(m,3H),7.40(d,J＝7.6Hz,1H),4.88 (q,J＝7.2Hz,1H),3.96(s,3H),1.78(d,J＝7.2Hz,3H).13C NMR(100MHz, CDCl3)δ164.3,158.3,139.3,134.0,132.4,131.0,129.0,127.6,126.2,125.6, 125.4,124.1,123.1,54.7,35.1,21.9.HRMS(EI)calculated for[M]+(C17H16N2O) m/z 264.1263,found m/z 264.1266.
化合物P19：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝40:1- 20:1)得到无色液体产物37.4mg，收率67％。
1H NMR(400MHz,CDCl3)δ8.07–8.00(m,1H),7.91–7.86(m,1H),7.89(dd, J＝7.6,2.4Hz,1H),7.51–7.44(m,5H),6.79(dd,J＝4.0,0.8Hz,1H),5.16(q,J ＝7.2Hz,1H),2.48(s,3H),1.87(d,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3) δ190.6,160.7,142.2,140.1,133.9,132.6,131.1,129.0,127.7,126.2,125.6,125.5, 125.4,124.1,123.2,36.7,26.4,22.9.HRMS(EI)calculated for[M]+(C18H16OS) m/z 280.0922,found m/z 280.0928.
化合物P20：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝8:1-4:1) 得到无色液体产物59.4mg，收率75％。
1H NMR(400MHz,CDCl3)δ8.07–8.01(m,1H),7.89–7.85(m,1H),7.84– 7.80(m,2H),7.79–7.75(m,1H),7.55–7.43(m,6H),4.84(t,J＝7.6Hz,1H), 2.99(s,3H),2.30–2.20(m,1H),2.19–2.08(m,1H),1.47–1.33(m,4H),1.32– 1.19(m,6H),0.88(t,J＝6.8Hz,3H).13CNMR(100MHz,CDCl3)δ151.9,139.0, 138.0,134.0,131.7,129.0,128.9,127.5,127.4,126.1,125.5,125.4,124.3,123.2, 46.2,44.4,36.1,31.7,29.6,29.1,28.0,22.6,14.0.HRMS(EI)calculated for [M]+(C25H30O2S)m/z 394.1967,found m/z 394.1966.
化合物P21：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝200:0- 200:1)得到无色液体产物44.4mg，收率54％。
1H NMR(400MHz,CDCl3)δ7.98–7.94(m,1H),7.93–7.89(m,1H),7.86(d,J ＝7.6Hz,1H),7.78(s,1H),7.77(s,2H),7.57–7.49(m,3H),7.34(d,J＝7.2Hz, 1H),5.14(dd,J＝8.4,6.0Hz,1H),4.12(dd,J＝12.4,6.0Hz,1H),4.02(dd,J＝ 12.4,8.4Hz,1H).13C NMR(100MHz,CDCl3)δ144.0,134.7,134.2,132.0(q,J ＝33.2Hz),131.1,129.3,128.7,128.4,126.9,126.0,125.3,125.0,123.2(q,J＝ 272.3Hz),122.5,121.3,55.1,45.7.19F NMR(376MHz,CDCl3)δ-62.74(s). HRMS(EI)calculated for[M]+(C20H13N3F6)m/z 409.1014,found m/z 409.1016.
化合物P22：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝20:0- 20:1)得到无色液体产物55.9mg，收率78％。
1H NMR(400MHz,CDCl3)δ8.08–8.03(m,1H),7.91–7.86(m,1H),7.82(d,J ＝8.0Hz,1H),7.56(d,J＝8.0Hz,2H),7.53–7.46(m,3H),7.42(d,J＝8.0Hz, 2H),7.38(d,J＝8.0Hz,1H),5.25(t,J＝7.2Hz,1H),4.84–4.77(m,1H),4.76– 4.69(m,1H),2.01(s,3H).13C NMR(100MHz,CDCl3)δ171.0,145.2,135.5, 134.1,131.6,129.1(q,J＝32.3Hz),129.0,128.8,128.0,126.5,125.7,125.5(q,J ＝3.8Hz),125.3,124.9,124.1(q,J＝270.4Hz),123.2,66.3,45.1,20.9.19F NMR (376MHz,CDCl3)δ-62.43(s).HRMS(EI)calculated for[M]+(C21H17F3O2)m/z 358.1181,found m/z 358.1176.
化合物P23：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝30:1- 15:1)得到淡黄色液体产物44.7mg，收率70％。
1H NMR(400MHz,CDCl3)δ8.09–8.04(m,2H),7.89(d,J＝8.0Hz,1H),7.87 –7.83(m,1H),7.78(d,J＝8.4Hz,1H),7.51–7.43(m,4H),7.41(d,J＝7.2Hz, 1H),7.34(t,J＝7.6Hz,1H),5.16(t,J＝7.2Hz,1H),4.11–4.01(m,2H),3.89(s, 3H),3.42(s,3H).13C NMR(100MHz,CDCl3)δ167.1,142.6,136.7,134.0,133.1, 131.7,130.3,129.4,128.9,128.5,127.8,127.6,126.2,125.4,125.3,125.1,123.4, 75.6,58.9,52.0,46.2.HRMS(EI)calculatedfor[M]+(C21H20O3)m/z 320.1412, found m/z 320.1408.
化合物P24:
该反应按照通用操作步骤1进行，柱层析分离(石油醚：二氯甲烷＝3:1-1:1) 得到无色液体产物60.0mg，收率67％。
1H NMR(400MHz,CDCl3)δ8.32(d,J＝8.8Hz,1H),7.84(d,J＝7.6Hz,1H), 7.81–7.75(m,3H),7.70–7.64(m,2H),7.56–7.44(m,8H),5.73(dd,J＝8.4, 6.8Hz),4.47(dd,J＝14.0,8.4Hz,1H),4.37(dd,J＝14.0,6.8Hz,1H).13C NMR (100MHz,CDCl3)δ168.3,145.0,136.0,134.0,131.6,128.9,128.86,128.81(q, J＝32.3Hz),128.0,126.6,125.7,125.5(q,J＝3.8Hz),125.4,125.0,124.0(q,J ＝270.4Hz),123.34,123.28,43.9,42.3.19F NMR(376MHz,CDCl3)δ-62.43(s). HRMS(EI)calculated for[M]+(C27H18F3NO2)m/z 445.1290,found m/z 445.1283.
化合物P25：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝100:0- 100:1)得到无色液体产物66.5mg，收率85％。
1H NMR(400MHz,CDCl3)δ8.02(d,J＝8.0Hz,1H),7.91–7.85(m,1H),7.80 (d,J＝7.6Hz,1H),7.55–7.45(m,4H),7.11(s,1H),6.91(t,J＝7.6Hz,2H),4.72 (t,J＝7.6Hz,1H),3.44(t,J＝6.4Hz,2H),2.45–2.33(m,1H),2.31–2.20(m, 1H),2.00–1.85(m,2H).13CNMR(100MHz,CDCl3)δ162.7(d,J＝247.7Hz), 148.5(d,J＝7.6Hz),137.9,134.9(d,J＝11.4Hz),134.1,131.6,129.0,127.7, 126.4,125.6,125.4,124.4,124.0,123.0,114.2(d,J＝24.6Hz),113.4(d,J＝21.8 Hz),45.1,34.4,33.5,30.9.19F NMR(376MHz,CDCl3)δ-110.71(t,J＝9.0Hz). HRMS(EI)calculated for[M]+(C20H17FClBr)m/z 390.0186,foundm/z 390.0189.
化合物P26：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝40:1- 20:1)得到淡黄色液体产物46.2mg，收率74％。
1H NMR(400MHz,CDCl3)δ8.12–8.07(m,1H),7.89–7.86(m,1H),7.78(d,J ＝8.0Hz,1H),7.53–7.44(m,3H),7.40(d,J＝7.2Hz,1H),7.27(s,1H),7.22– 7.14(m,3H),5.38(t,J＝8.0Hz,1H),3.62(s,3H),3.21(dd,J＝16.0,7.2Hz,1H), 3.13(dd,J＝16.0,8.4Hz,1H).13C NMR(100MHz,CDCl3)δ172.0,145.4,138.0, 134.4,134.0,131.3,129.8,128.9,127.9,127.8,126.8,126.3,126.1,125.6,125.3, 124.1,123.4,51.8,42.2,40.9.HRMS(EI)calculated for[M]+(C20H17O2Cl)m/z 324.0917,found m/z 324.0930.
化合物P27：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝40:1- 20:1)得到淡黄色液体产物59.2mg，收率84％。
1H NMR(400MHz,CDCl3)δ8.30(d,J＝8.8Hz,1H),7.96(d,J＝8.4Hz,1H), 7.85(d,J＝8.0Hz,2H),7.79(d,J＝7.6Hz,1H),7.55(t,J＝7.2Hz,1H),7.46(t, J＝7.2Hz,1H),7.29(d,J＝8.4Hz,3H),4.92(q,J＝7.2Hz,1H),2.54(s,3H), 1.76(d,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ197.6,151.8,140.5,135.2, 132.7,132.1,129.5,128.7,128.0,127.6,126.9,126.8,124.9,124.1,122.0,40.6, 26.5,22.2.HRMS(EI)calculated for[M]+(C20H17OBr)m/z 352.0463,found m/z 352.0470.
化合物P28：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝80:1- 40:1)得到无色液体产物32.5mg，收率50％。
1H NMR(400MHz,CDCl3)δ8.94(d,J＝8.4Hz,1H),8.16(d,J＝8.0Hz,1H), 8.01(d,J＝8.4Hz,1H),7.59(t,J＝7.2Hz,1H),7.50(t,J＝7.2Hz,1H),7.44(d, J＝7.6Hz,1H),6.75–6.68(m,2H),6.66–6.58(m,1H),4.92(q,J＝7.2Hz,1H), 4.01(s,3H),1.76(d,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ168.0,163.1 (dd,J＝246.7,12.4Hz),150.0(t,J＝8.5Hz),145.3,131.72,131.70,129.6,127.2, 126.59,126.57,126.47,123.8,123.2,110.4(dd,J＝18.0,5.7Hz),101.8(t,J＝ 24.7Hz),52.2,40.6,22.0.19F NMR(376MHz,CDCl3)δ-109.74(t,J＝8.3Hz). HRMS(EI)calculated for[M]+(C20H16O2F2)m/z 326.1118,found m/z 326.1110.
化合物P29：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝60:0- 30:1)得到无色液体产物39.3mg，收率57％。
1H NMR(400MHz,CDCl3)δ7.81(d,J＝8.8Hz,1H),7.72(d,J＝8.4Hz,1H), 7.69(s,1H),7.51(d,J＝2.0Hz,1H),7.32(dd,J＝8.8,1.6Hz,1H),7.23(dd,J＝ 8.8,2.4Hz,1H),7.15–7.04(m,3H),4.59(q,J＝7.2Hz,1H),2.40(s,3H),1.70 (d,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ169.7,160.2(d,J＝248.3Hz), 148.1,141.7,132.6(d,J＝10.6Hz),132.4,131.7(d,J＝14.5Hz),131.4,129.4(d, J＝5.3Hz),129.2,127.8,127.2,125.2,124.4(d,J＝3.8Hz),121.3,118.3,116.1 (d,J＝25.8Hz),37.2(d,J＝2.3Hz),21.2,20.4.19F NMR(376MHz,CDCl3)δ- 115.20(t,J＝8.6Hz).HRMS(EI)calculated for[M]+(C20H16O2FCl)m/z 342.0823, found m/z 342.0830.
化合物P30：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝200:1- 80:1)得到无色液体产物34.0mg，收率43％。
1H NMR(400MHz,CDCl3)δ7.79–7.72(s,3H),7.71(s,2H),7.67(s,1H),7.62 (s,1H),7.39(dd,J＝8.4,1.2Hz,1H),7.22(dd,J＝8.4,1.6Hz,1H),4.43(q,J＝ 7.2Hz,1H),2.83(q,J＝7.6Hz,2H),1.78(d,J＝7.2Hz,3H),1.34(t,J＝7.6Hz, 3H).13C NMR(100MHz,CDCl3)δ148.9,141.9,140.6,132.6,131.9,131.6(q,J ＝33.0Hz),128.1,127.8,127.7,127.6,126.1,125.4,125.3,123.4(q,J＝271.4 Hz),120.3(t,J＝3.6Hz),44.6,29.0,21.6,15.5.19F NMR(376MHz,CDCl3)δ- 62.71(s).HRMS(EI)calculated for[M]+(C22H18F6)m/z 391.1313,found m/z 393.1309.
化合物P31：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝8:1-4:1) 得到无色液体产物36.8mg，收率60％。
1H NMR(400MHz,CDCl3)δ7.86(d,J＝8.4Hz,2H),7.70(d,J＝8.0Hz,2H), 7.53(t,J＝7.6Hz,1H),7.47(t,J＝7.6Hz,1H),7.37(d,J＝8.4Hz,2H),7.34(d, J＝7.2Hz,1H),7.08(d,J＝6.8Hz,1H),4.97(dd,J＝8.8,4.0Hz,1H),4.01(dd, J＝17.6,8.8Hz,1H),3.36(dd,J＝17.6,4.0Hz,1H),3.05(s,3H).13C NMR(100 MHz,CDCl3)δ152.3,147.3,143.1,138.6,138.5,131.5,128.7,128.3,128.1,127.8, 123.5,122.8,120.2,119.6,49.3,44.5,41.4.HRMS(EI)calculated for [M]+(C19H16O2S)m/z 308.0871,found m/z 308.0866.
化合物P32：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝200:0- 200:1)得到无色液体产物49.2mg，收率55％。
1H NMR(400MHz,CDCl3)δ7.92–7.86(m,2H),7.83(d,J＝8.0Hz,1H),7.66 –7.62(m,2H),7.59–7.53(m,1H),7.50–7.41(m,4H),7.24–7.16(m,3H),7.01 –6.95(m,2H),5.12(dd,J＝10.0,5.6Hz,1H),3.62(dd,J＝13.6,5.6Hz,1H), 3.35(dd,J＝13.6,10.0Hz,1H).13CNMR(100MHz,CDCl3)δ146.6,138.8, 137.8,134.1,131.4,131.3(q,J＝32.9Hz),129.1,129.0,128.4,128.3,128.1,126.6, 126.4,125.7,125.4,124.7,123.2(q,J＝271.4Hz),123.0,120.4,48.3,42.5.19F NMR(376MHz,CDCl3)δ-62.80(s).HRMS(DART)calculated for[M+NH4]+ (C26H22NF6)m/z 462.1651,found m/z 462.1648.
化合物P33：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝200:0- 200:1)得到无色液体产物49.2mg，收率73％。
1H NMR(400MHz,CDCl3)δ7.95(d,J＝8.0Hz,1H),7.89(d,J＝8.0Hz,1H), 7.79(d,J＝8.0Hz,1H),7.53–7.36(m,6H),7.35–7.25(m,4H),7.10(d,J＝7.2 Hz,2H),6.91(d,J＝7.2Hz,1H),6.34(s,1H).13C NMR(100MHz,CDCl3)δ 144.7,142.7,138.9,133.9,133.0(q,J＝1.2Hz),131.6,130.8(q,J＝32.0Hz), 129.5,128.82,128.80,128.6,127.7,127.6,126.7,126.3,126.2(q,J＝3.9Hz), 125.6,125.2,124.1(q,J＝271.0Hz),124.0,123.4(q,J＝3.5Hz),52.9.19F NMR (376MHz,CDCl3)δ-62.40(s).HRMS(EI)calculated for[M]+(C24H17F3)m/z 362.1282,found m/z 362.1288.
化合物P34：
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝80:1- 40:1)得到无色液体产物74.8mg，收率72％。
1H NMR(400MHz,CDCl3)δ7.97(t,J＝9.6Hz,2H),7.90–7.84(m,2H),7.66 (s,2H),7.58–7.50(m,2H),7.49–7.44(m,1H),7.34(t,J＝7.6Hz,2H),7.30– 7.25(m,1H),7.24–7.15(m,4H),7.06(d,J＝8.0Hz,2H),6.93(d,J＝7.2Hz, 1H),6.44(s,1H),2.99(s,4H).13CNMR(100MHz,CDCl3)δ146.8,141.5,140.6, 139.1,138.2,134.0,131.6(q,J＝32.6Hz),131.5,129.6,129.3,129.0,128.9,128.5, 128.3,128.0,127.5,126.5,125.9,125.8,125.2,123.7,123.3(q,J＝271.0Hz), 120.7(t,J＝3.8Hz),52.4,37.7,37.5.19F NMR(376MHz,CDCl3)δ-62.66(s). HRMS(DART)calculated for[M+NH4]+(C33H28NF6)m/z552.2120,found m/z 552.2112.
化合物P35：
该反应按照通用操作步骤2进行，柱层析分离(石油醚：乙酸乙酯＝300:1- 150:1)得到无色液体产物39.9mg，收率63％。
1H NMR(400MHz,CDCl3)δ7.99(s,1H),7.89(d,J＝7.6Hz,1H),7.57(d,J＝7.6Hz,2H),7.52(d,J＝8.0Hz,2H),7.45–7.37(m,4H),7.36–7.25(m,4H), 4.25(q,J＝7.2Hz,1H),3.91(s,3H),1.71(d,J＝7.2Hz,3H).13C NMR(100 MHz,CDCl3)δ167.2,146.6,144.8,140.8,139.1,132.4,130.2,128.7,128.6,128.5, 127.9,127.4,127.2,127.1,127.0,52.1,44.3,21.7.HRMS(EI)calculated for [M]+(C22H20O2)m/z 316.1463,found m/z 314.1465.
化合物P36：
该反应按照通用操作步骤2进行，柱层析分离(石油醚：乙酸乙酯＝300:0- 300:1)得到白色固体产物44.5mg，收率53％。
1H NMR(400MHz,CDCl3)δ7.78(s,2H),7.72(s,1H),7.57(t,J＝8.0Hz,4H), 7.44(t,J＝7.6Hz,2H),7.35(d,J＝8.0Hz,3H),3.62(d,J＝10.8Hz,1H),2.65– 2.52(m,1H),0.97(d,J＝6.0Hz,3H),0.91(d,J＝6.0Hz,3H).13C NMR(100 MHz,CDCl3)δ147.3,141.9,140.5,139.7,131.6(q,J＝33.0Hz),128.7,128.2, 128.0,127.6,127.3,127.0,123.4(q,J＝271.4Hz),120.2(m),60.1,31.9,21.64, 21.60.19F NMR(376MHz,CDCl3)δ-62.71(s).HRMS(EI)calculated for[M]+ (C24H20F6)m/z 422.1469,found m/z 422.1482.
化合物P37：
该反应按照通用操作步骤2进行，柱层析分离(石油醚：乙酸乙酯＝300:1- 150:1)得到无色液体产物32.6mg，收率50％。
1H NMR(400MHz,CDCl3)δ7.35–7.29(m,2H),7.20–7.16(m,2H),7.15– 7.02(m,4H),7.01–6.97(m,2H),6.95–6.91(m,2H),4.41(q,J＝7.2Hz,1H), 1.60(d,J＝7.2Hz,3H).13CNMR(100MHz,CDCl3)δ160.2(d,J＝248.3Hz), 157.2,155.6,139.2,132.4(d,J＝10.6Hz),132.0(d,J＝15.2Hz),129.7,129.2(d, J＝5.3Hz),128.6,124.4(d,J＝3.8Hz),123.1,118.8,116.2(d,J＝25.8Hz),36.6, 20.7.19F NMR(376MHz,CDCl3)δ-115.27(dd,J＝9.4,7.5Hz).HRMS(EI) calculated for[M]+(C20H16OFCl)m/z 326.0874,found m/z 326.0872.
化合物P38：
该反应按照通用操作步骤2进行，柱层析分离(石油醚：乙酸乙酯＝200:0- 200:1)得到无色液体产物49.2mg，收率53％。
1H NMR(400MHz,CDCl3)δ7.76(s,1H),7.73(s,2H),7.70(d,J＝6.8Hz,1H), 7.67(d,J＝7.6Hz,1H),7.45(d,J＝6.8Hz,1H),7.37–7.30(m,2H),7.28(s,1H), 7.16(d,J＝7.6Hz,1H),4.36(q,J＝7.2Hz,1H),2.20–2.05(m,8H),1.76(d,J ＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ154.9,154.3,149.1,143.4,139.0, 138.4,131.6(q,J＝32.6Hz),127.8,127.4,126.7,126.0,123.4(q,J＝271.7Hz), 122.8,121.9,120.2,119.8,119.5,57.6,44.8,39.8,39.7,26.9,22.0.19F NMR(376 MHz,CDCl3)δ-62.73(s).HRMS(DART)calculatedfor[M+H]+(C27H23F6)m/z 461.1698,found m/z 461.1692.
化合物P39：
该反应按照通用操作步骤2进行，柱层析分离(石油醚：乙酸乙酯＝30:0- 15:1)得到无色液体产物56.4mg，收率83％。
1H NMR(400MHz,CDCl3)δ8.10–8.04(m,2H),7.78(d,J＝8.4Hz,1H),7.59 –7.47(m,7H),7.35(t,J＝7.6Hz,1H),7.28(d,J＝7.6Hz,1H),5.33(q,J＝7.2 Hz,1H),1.81(d,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ166.8,152.3, 151.7,139.7,135.3,133.6,132.0,130.9,128.9,128.5,127.4,125.3,123.6,119.9, 119.1,109.6,40.8,20.5.HRMS(DART)calculated for[M+H]+(C22H17N2S)m/z 341.1107,found m/z 341.1103.
化合物P40：
该反应按照通用操作步骤2进行，柱层析分离(石油醚：乙酸乙酯＝30:0- 15:1)得到无色液体产物72.5mg，收率71％。
1H NMR(400MHz,CDCl3)δ7.91(d,J＝8.4Hz,1H),7.75(d,J＝8.4Hz,2H), 7.69(s,1H),7.60(s,2H),7.54(d,J＝3.2Hz,1H),7.31(t,J＝7.6Hz,1H),7.23 (d,J＝8.4Hz,2H),7.07(d,J＝7.2Hz,1H),6.50(d,J＝4.0Hz,1H),4.57(q,J＝ 7.2Hz,1H),2.34(s,3H),1.72(d,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ 148.2,145.1,136.5,135.1,134.8,131.5(q,J＝32.6Hz),129.9,129.4,127.6,126.8, 126.4,124.9,123.3(q,J＝271.7Hz),121.0,120.3(t,J＝3.8Hz),112.3,106.6, 41.7,21.5,21.3.19F NMR(376MHz,CDCl3)δ-62.78.HRMS(DART)calculated for[M+H]+(C25H20O2NF6S)m/z 512.1113,found m/z512.1109.
化合物P41：
该反应按照通用操作步骤2进行，柱层析分离(石油醚：乙酸乙酯＝40:0- 20:1)得到白色固体产物47.0mg，收率78％。
1H NMR(400MHz,CDCl3)δ7.88(d,J＝2.4Hz,1H),7.71(d,J＝1.6Hz,1H), 7.64–7.59(m,2H),7.32–7.27(m,2H),7.16–7.03(m,3H),6.44(t,J＝2.0Hz, 1H),4.45(q,J＝7.2Hz,1H),1.63(d,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3) δ160.2(d,J＝247.5Hz),142.7,140.9,138.6,132.6(d,J＝9.9Hz),131.6(d,J＝ 14.5Hz),129.1(d,J＝4.5Hz),128.3,126.6,124.4(d,J＝3.8Hz),119.2,116.2 (d,J＝25.8Hz),107.4,36.8,20.5.19FNMR(376MHz,CDCl3)δ-115.04(t,J＝ 8.6Hz).HRMS(EI)calculated for[M]+(C17H14N2FCl)m/z 300.0830,found m/z 300.0835.
化合物P42：
该反应按照通用操作步骤2进行，柱层析分离(石油醚：乙酸乙酯＝20:1- 10:1)得到淡黄色液体产物54.4mg，收率71％。
1H NMR(400MHz,CDCl3)δ8.23(s,1H),8.07(d,J＝8.4Hz,1H),7.93(d,J＝ 7.6Hz,1H),7.88(d,J＝8.0Hz,1H),7.58(s,1H),7.51–7.46(m,2H),7.45–7.39 (m,2H),7.36(t,J＝7.2Hz,1H),7.23(d,J＝8.0Hz,1H),4.41(q,J＝7.2Hz,1H), 2.82(s,3H),1.78(d,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ170.0,147.2, 145.1,139.1,138.6,131.0,130.6(q,J＝31.9Hz),128.8,127.0,126.3,124.7, 124.19(q,J＝271.0Hz),124.18(q,J＝3.8Hz),123.6,123.4,123.0(q,J＝3.8 Hz),119.74,119.68,115.8,115.7,45.2,27.6,22.0.19FNMR(376MHz,CDCl3)δ -62.39(s).HRMS(DART)calculated for[M+H]+(C23H19ONF3)m/z382.1413, found m/z 382.1410.
化合物P43:
该反应按照通用操作步骤2进行，柱层析分离(石油醚：乙酸乙酯＝40:1- 20:1)得到无色液体产物96.2mg，收率83％。
1H NMR(400MHz,CDCl3)δ8.35(dd,J＝8.8,4.4Hz,2H),7.83(d,J＝2.0Hz, 1H),7.77(d,J＝7.6Hz,2H),7.72(s,1H),7.62(s,2H),7.55–7.47(m,2H),7.44 (dd,J＝8.8,2.0Hz,1H),7.34(t,J＝8.0Hz,2H),7.09(d,J＝8.0Hz,1H),5.05(q, J＝7.2Hz,1H),1.80(d,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ147.1, 139.45,139.38,137.3,136.8,134.1,131.8(q,J＝32.7Hz),129.7,129.1,128.2, 128.0,127.0,126.8,126.4,123.2(q,J＝270.9Hz),123.0,122.8,122.4,120.7, 116.2,114.0,41.0,21.5.19F NMR(376MHz,CDCl3)δ-62.81(s).HRMS(DART) calculated for[M+NH4]+(C28H22O2N2ClF6S)m/z 599.0989,foundm/z 599.0978. 化合物P44:
该反应按照通用操作步骤2进行，柱层析分离(石油醚：乙酸乙酯＝60:1-3 个0:1)得到无色液体产物36.7mg，收率32％。
1H NMR(400MHz,CDCl3)δ7.83(s,1H),7.62(s,2H),7.51(dd,J＝8.4,5.6Hz, 2H),7.37(d,J＝8.0Hz,1H),7.13–7.02(m,5H),6.58(d,J＝3.2Hz,1H),5.88 (s,1H),2.24(s,3H).13C NMR(100MHz,CDCl3)δ162.4(d,J＝245.7Hz),144.9, 143.6,143.2,142.1,135.2,132.6,131.9(q,J＝32.6Hz),131.2,130.8,130.1(d,J ＝3.1Hz),128.9,128.4,127.3(d,J＝7.6Hz),123.1(q,J＝271.7Hz),122.8,121.4 (t,J＝3.0Hz),120.2,115.9(d,J＝21.2Hz),48.1,19.3.19F NMR(376MHz, CDCl3)δ-62.72(s),-114.17(m).HRMS(DART)calculated for[M]+ (C26H16BrF7S)m/z 572.0039,found m/z 572.0036.
化合物P45:
该反应按照通用操作步骤2进行，柱层析分离(石油醚：乙酸乙酯＝20:1- 10:1)得到白色固体产物73.9mg，收率70％。
1H NMR(400MHz,CDCl3)δ8.01(s,1H),7.71(d,J＝7.6Hz,1H),7.45(s,1H), 7.35–7.25(m,3H),7.07(d,J＝8.0Hz,1H),7.01(d,J＝7.2Hz,1H),6.98(s,2H), 4.48(s,1H),1.81(s,3H).13C NMR(100MHz,CDCl3)δ167.9,147.4,142.5, 140.5,135.7,132.8,132.1,131.6(q,J＝33.0Hz),128.9,128.5,127.6,124.7,123.1, 122.69(q,J＝271.4Hz),122.70,120.9,76.2,56.1,28.1.19F NMR(376MHz, CDCl3)δ-63.19(s).HRMS(DART)calculated for[M+H]+(C24H15BrF6NO)m/z 526.0236,found m/z 526.0230.
化合物P46:
该反应按照通用操作步骤2进行，反应规模0.09mmol。柱层析分离(石油醚：乙酸乙酯＝20:1-10:1)得到无色液体产物34.5mg，收率65％。
1H NMR(400MHz,CDCl3)δ7.86(d,J＝8.4Hz,1H),7.79–7.74(m,1H),7.52 (s,1H),7.38–7.29(m,3H),7.05(s,1H),7.03–6.98(m,3H),4.73(s,1H),4.54 (d,J＝11.2Hz,1H),4.44(d,J＝11.2Hz,1H),1.96(s,3H).13C NMR(100MHz, CDCl3)δ170.2,168.5,146.5,143.5,141.6,138.6,137.6,132.9,132.8,131.9(q,J ＝33.4Hz),129.7,128.0,125.0,123.5,123.0,122.6(q,J＝271.8Hz),121.3(m), 120.4(q,J＝255.8Hz),119.5,118.1,77.4,67.8,52.2,20.4.19F NMR(376MHz, CDCl3)δ-58.28(s),-63.28(s).HRMS(DART)calculated for [M+H]+(C27H17NO4F9)m/z 590.1008,found m/z 590.0997.
化合物P47:
该反应按照通用操作步骤2进行，反应规模0.1mmol。柱层析分离(正戊烷) 得到无色液体产物27.0mg，收率45％。粗谱分析表明产物的非对映选择性 为1:1。
1H NMR(400MHz,CDCl3)δ7.77(s,1H),7.66(s,1H),7.65(s,1H),7.02(d,J＝7.2Hz,1H),6.67(t,J＝7.6Hz,1H),6.45(d,J＝7.6Hz,1H),4.35–4.19(m,1H), 2.25–2.21(m,3H),2.18–2.00(m,1H),1.96–1.84(m,1H),1.73–1.62(m,1H), 1.55–1.47(m,2H),1.45–0.98(m,21H),0.95–0.82(m,12H).13C NMR(150 MHz,CDCl3)δ152.3/152.1,148.4/148.3,131.9(q,J＝33.3Hz),129.54/129.46, 128.9,126.9/126.8,126.8/126.7,123.3(q,J＝271.2Hz),122.0,120.7,119.5/119.4, 76.4/76.2,43.1/42.0,42.7,40.0/39.4,39.8/39.4,37.43/37.28,37.41/37.37,36.6, 32.8,32.7,32.6,28.0/26.6,24.8,24.5/24.4,22.7/22.6,22.4,21.2/20.7,19.73, 19.68/19.60,16.2.19F NMR(376MHz,CDCl3)δ-62.70/-62.71(s).HRMS(DART) calculated for[M+H]+(C35H49OF6)m/z 599.3682,found m/z 599.3676.
化合物P48:
该反应按照通用操作步骤2进行，反应规模0.05mmol。柱层析分离(石油 醚：乙酸乙酯＝5:1-3个:1)得到无色液体产物24.8mg，收率63％。粗谱分 析表明产物的非对映选择性为1.4:1。
1H NMR(400MHz,CDCl3)δ7.76(s,1H),7.46(s,2H),7.41(d,J＝8.4Hz,1H), 7.32–7.27(m,1H),6.92–6.83(m,4H),6.78(d,J＝1.6Hz,1H),5.96/5.94(s, 1H),5.25(t,J＝9.6Hz,1H),5.20–5.13(m,1H),5.06–4.95(m,1H),4.30–4.19 (m,2H),4.16–4.09(m,1H),4.08–3.97(m,2H),3.80–3.73(m,1H),2.05/2.04 (s,6H),1.98(s,3H),1.72/1.69(s,3H),1.45–1.38(m,3H).13C NMR(150MHz, CDCl3)δ170.65/170.63,170.3,169.48/169.46,168.62/168.58,158.2,145.7/145.4, 140.0/139.8,135.5,135.0/134.9,132.2/131.8,131.69/131.66(q,J＝33.3Hz), 130.43/130.39,130.36,129.58/129.53,129.24,127.1/127.0,123.26/123.23(q,J＝ 271.4Hz),120.8,114.81/114.80,79.36/79.33,76.0,74.0/73.9,72.5/72.4,68.3, 63.4,62.2/62.0,52.4/52.3,20.61,20.58,20.2,20.1,14.81,14.78.19F NMR(376 MHz,CDCl3)δ-62.65/-62.70(s).HRMS(DART)calculated for[M+H]+(C37H36O10ClF6)m/z 789.1896,found m/z 789.1887.
化合物P49:
该反应按照通用操作步骤1进行，柱层析分离(石油醚：乙酸乙酯＝8:1-4:1) 得到无色液体产物63.8mg，收率96％。
1H NMR(400MHz,CDCl3)δ7.90–7.85(m,2H),7.78(d,J＝8.0Hz,1H),7.49 (t,J＝8.4Hz,1H),7.44(t,J＝8.4Hz,1H),7.35(d,J＝9.2Hz,1H),7.14(d,J＝ 8.4Hz,2H),6.99(d,J＝8.8Hz,2H),4.96(dd,J＝6.0,2.0Hz,1H),3.24–3.11 (m,2H),2.25(s,3H).13C NMR(100MHz,CDCl3)δ169.2,166.9,149.8,149.6, 137.9,131.0,130.8,130.0,128.7,128.0,127.5,125.3,122.9,122.2,117.4,117.3, 37.2,36.8,21.0.HRMS(DART)calculated for[M+H]+(C21H17O4)m/z 333.1121, found m/z 333.1119。

Claims (10)

1.一种合成如式Ⅲ所示的1，1-二芳基取代烷烃类化合物的方法，其特征在于，所述方法包括以下步骤：
在气体保护下，在铜催化剂、双氮配体、碱和氧化剂的作用下，式I化合物和式II化合物在有机溶剂中进行如下反应，从而得到式III化合物；
其中，
Ar1为取代或未取代的C6-C14芳基、或取代或未取代的C2-C14杂芳基,或者Ar1与R形成如下成环结构： 其中，
每个R1相同或不同，各自独立地选自氢、C1-C6烷基、卤素、-OR2、-CO2R3、苯基、C2-C4酯基、氰基和对甲基苯磺酰基中的一个或多个，R2选自C1-C4烷基或C1-C4酰基，R3选自C1-C4烷基；当取代基为多个时，所述的取代基相同或不同；
所述取代的C6-C14芳基和取代的C2-C14杂芳基中的取代基各自独立地选自卤素、氰基、C1-C4醛基、C1-C4烷基、C1-C4烷氧基、C1-C4卤代烷基、C1-C4卤代烷氧基、C6-C10芳基、C2-C6杂芳基、和-OR2’中的一个或多个，或者所述取代的C6-C14芳基和取代的C2-C14杂芳基中的取代基与其母核形成如下结构：其中R1’为C1-C4烷基，R2’为C6-C10芳基；每个R1相同或不同，各自独立地选自氢、C1-C6烷基、卤素、-OR2、-CO2R3、苯基、C2-C4酯基、氰基和对甲基苯磺酰基中的一个或多个，R2选自C1-C4烷基或C1-C4酰基，R3选自C1-C4烷基；R4选自C1-C4烷基或-SO2Ph；当取代基为多个时，所述的取代基相同或不同；
所述取代或未取代的C2-C14杂芳基和所述C2-C6杂芳基中的杂原子各自独立地选自O、N和S中的一个或多个，杂原子的个数为1-3个，当杂原子为多个时，所述的杂原子相同或不同；
Ar2为取代或未取代的C6-C14芳基、或取代或未取代的C2-C14杂芳基，所述取代的C6-C14芳基和取代的C2-C14杂芳基中的取代基各自独立地选自卤素、氰基、C1-C4醛基、C1-C4烷基、C1-C4烷氧基、C1-C4卤代烷基、C1-C4卤代烷氧基、和-SO2R3’中的一个或多个，其中R1’和R3’各自独立地为C1-C4烷基，当取代基为多个时，所述的取代基相同或不同；所述取代或未取代的C2-C14杂芳基中的杂原子选自O、N和S中的一个或多个，杂原子的个数为1-3个，当杂原子为多个时，所述的杂原子相同或不同；
R选自取代或未取代的C1-C20直链或支链烷基、取代或未取代的C6-C10芳基、或取代或未取代的C2-C10杂芳基；所述取代的C1-C20直链或支链烷基的取代基选自-N3、卤素、C6-C10芳基、-OR5和-CO2R5中的一个或多个，其中每个R5相同或不同，各自独立为C1-C6烷基；所述取代的C6-C10芳基中的取代基选自以下任意一个或多个基团：C1-C4烷氧基和-R6Ph，其中R6为C1-C4烷基；所述取代的C2-C10杂芳基的取代基为卤素取代的C6-C10芳基；当取代基为多个时，所述的取代基相同或不同；所述取代或未取代的C2-C10杂芳基中的杂原子选自O、N和S中的一个或多个，杂原子的个数为1-3个，当杂原子为多个时，所述的杂原子相同或不同。
2.如权利要求1所述的方法，其特征在于，
Ar1为取代或未取代的C6-C10芳基、或取代或未取代的C2-C10杂芳基，所述取代的C6-C10芳基和取代的C2-C10杂芳基中的取代基各自独立地选自F、Cl、Br、I、氰基、C1-C4醛基、甲基、乙基、正丙基、异丙基、正丁基、叔丁基、异丁基、三氟甲基、三氟甲氧基、甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、异丁氧基、叔丁氧基、苯基、-OPh、-SO2Ph、 中的一个或多个，其中R9选自C1-C4烷基或C1-C4酰基；当取代基为多个时，所述的取代基相同或不同；
优选的Ar1选自 其中每个R1相同或不同，各自独立地选自氢、C1-C6烷基、卤素、-OR2、-CO2R3、苯基、C2-C4酯基、氰基和对甲基苯磺酰基中的一个或多个，R2选自C1-C4烷基或C1-C4酰基，R3选自C1-C4烷基；R7与R8各自独立地选自氢或C1-C6烷基、或者R7与R8形成3-7元碳环；R9选自C1-C4烷基或C1-C4酰基；X1、X2和X3各自独立地选自O、S或N；当取代基为多个时，所述的取代基相同或不同；
R选自取代或未取代的C1-C16直链或支链烷基、取代或未取代的C6-C10芳基、或取代或未取代的C2-C8杂芳基；所述取代的C1-C16直链或支链烷基的取代基选自-N3、F、Cl、Br、I、苯基、溴乙基、甲氧基、乙氧基、 中的一个或多个；所述取代的C6-C10芳基的取代基选自甲氧基、乙氧基或苯乙基；所述取代的C2-C8杂芳基的取代基为氟代苯基；当取代基为多个时，所述的取代基相同或不同；所述取代或未取代的C2-C8杂芳基中的杂原子选自O、N和S中的一个或多个，杂原子的个数为1-3个，当杂原子为多个时，所述的杂原子相同或不同；
优选的R为甲基、-CH2N3、苯基、苯甲基、正庚基、异丙基、异丁基、-C3H6Br、-CH2OCH3、-CH2OAc、-CH2CO2CH3、-Ph-CH2-CH2-Ph或-PhOEt；
所述Ar1与R形成的成环结构优选为
Ar2为取代或未取代的C6-C10芳基、或取代或未取代的C2-C8杂芳基，所述取代的C6-C10芳基和取代的C2-C8杂芳基中的取代基各自独立地选自F、Cl、Br、I、甲基、乙基、正丙基、异丙基、正丁基、叔丁基、异丁基、-SO2CH3、氰基、C1-C4醛基、三氟甲基、三氟甲氧基、乙酰氧基、甲氧基和乙氧基中的一个或多个；当取代基为多个时，所述的取代基相同或不同；
优选的Ar2为其中每个R10相同或不同，各自独立地选自氢、F、Cl、Br、I、甲基、乙基、正丙基、异丙基、正丁基、叔丁基、异丁基、-SO2CH3、氰基、C1-C4醛基、三氟甲基、三氟甲氧基、乙酰氧基、甲氧基和中的一个或多个；X4选自O、S或N；当取代基为多个时，所述的取代基相同或不同。
3.如权利要求1所述的方法，其特征在于，所述的铜催化剂选自铜粉、碘化亚铜、氯化亚铜、溴化亚铜、氧化亚铜、醋酸亚铜、三氟甲磺酸亚铜和苯的2:1摩尔比复合物、噻吩甲酸亚铜、溴化亚铜的二甲硫醚复合物、四乙腈六氟磷酸铜、四乙腈三氟甲磺酸铜、四乙腈四氟硼酸铜、氯化铜、溴化铜、氟化铜、醋酸铜和三氟甲磺酸铜中的一种或多种，优选为碘化亚铜、四乙腈四氟硼酸铜、三氟甲磺酸铜和醋酸亚铜中的一种或多种，更优选为醋酸亚铜。
4.如权利要求1所述的方法，其特征在于，所述的双氮配体选自
其中R8’、R9’、R10’、R11’各自独立地选自氢、卤素、C2-C4酯基、氰基、C1-C6烷基和C6-C10芳基中的一个或多个，当取代基为多个时，所述的取代基相同或不同；优选为更优选为
5.如权利要求1所述的方法，其特征在于，
所述的气体为氮气或氩气；
和/或，所述的氧化剂为N-氟代双苯磺酰胺；
和/或，所述的碱选自碳酸锂、碳酸钠、碳酸钾、碳酸镁、碳酸钡、碳酸钙、碳酸铷、碳酸铯、碳酸银、碳酸铵、碳酸氢钠、碳酸氢钾、碳酸氢铵、磷酸钾、磷酸锂、氟化锂、氟化钠、氟化钾、氟化铯、氟化银、叔丁醇锂、叔丁醇钠、叔丁醇钾、甲醇锂、甲醇钠、乙醇钠、氢氧化钠、氢氧化钾、氢化钠、氢化钾、乙酸钠、乙酸钾、三乙胺、二异丙基乙基胺和三乙烯二胺中的一种或多种，优选碳酸锂、碳酸钠、碳酸钾、碳酸镁、碳酸铷、碳酸铯、碳酸铵、碳酸氢钠和碳酸氢钾中的一种或多种，更优选碳酸锂；
和/或，所述的有机溶剂为正己烷、乙腈、苯、氯苯、溴苯、氟苯、三氟甲苯、六氟苯、二氯甲烷、二氯乙烷、三氯甲烷、四氯化碳、1,1,2,2-四氯乙烷、丙酮、乙醚、四氢呋喃、乙二醇二甲醚、叔丁基甲基醚、1,4-二氧六环、甲醇、乙醇、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、N-甲基吡咯烷酮、六甲基磷酰胺和二甲亚砜中的一种或多种，优选苯和N,N-二甲基乙酰胺混合溶剂，混合比例为体积比9:1-1:9，优选的混合比例为体积比4:1。
6.如权利要求1所述的方法，其特征在于，
所述的铜催化剂，用量为式I化合物的1-50％摩尔当量，优选5％-30％摩尔当量，更优选10％摩尔当量；
和/或，所述的双氮配体，用量为式I化合物的1-60％摩尔当量，优选5％-30％摩尔当量，更优选12％摩尔当量；
和/或，所述的式Ⅱ化合物，用量为式I化合物的100-500％摩尔当量，优选200-300％摩尔当量，更优选200％摩尔当量；
和/或，所述的氧化剂，用量为式I化合物的100-400％摩尔当量，优选250-300％摩尔当量；
和/或，所述的碱，用量为式I化合物的50-300％摩尔当量，优选200％摩尔当量。
7.如权利要求1所述的方法，其特征在于，所述的铜催化剂与双氮配体的摩尔比为2:1-1:3，优选1:1.2。
8.如权利要求1所述的方法，其特征在于，所述的式I化合物、氧化剂和式II化合物的摩尔比为1:1:1-1:4:5，优选1:2.5:2—1:3:3。
9.如权利要求1所述的方法，其特征在于，所述的式I化合物的浓度为0.01-1.0摩尔/升，优选0.1-0.2摩尔/升。
10.如权利要求1所述的方法，其特征在于，所述反应温度为0-80℃，优选20-30℃；
和/或，所述反应时间为4-24小时。
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CN108675935A (zh) * 2018-06-13 2018-10-19 南昌航空大学 一种1,1-二芳基烷烃类化合物的制备方法
CN108675935B (zh) * 2018-06-13 2020-08-28 南昌航空大学 一种1,1-二芳基烷烃类化合物的制备方法
CN109232289A (zh) * 2018-09-10 2019-01-18 绍兴文理学院 一种n,n-二芳基酰胺衍生物的制备方法
CN109232289B (zh) * 2018-09-10 2021-04-13 绍兴文理学院 一种n,n-二芳基酰胺衍生物的制备方法
CN110194713A (zh) * 2019-02-25 2019-09-03 广东工业大学 一种ɑ, β不饱和酮化合物及其制备方法和应用
CN110483385A (zh) * 2019-08-12 2019-11-22 广东石油化工学院 一种棒-线状nnn三齿配体化合物及其制备方法和应用
CN113173854A (zh) * 2021-04-23 2021-07-27 中国科学院上海有机化学研究所 手性β-酰氧基羧酸酯类化合物的制备方法
CN113173854B (zh) * 2021-04-23 2023-07-07 中国科学院上海有机化学研究所 手性β-酰氧基羧酸酯类化合物的制备方法

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