一种多环芳烃化合物、合成方法及用途与流程

本发明涉及一种多环芳烃、合成方法以及用途，系使用多取代的3-芳基-2-萘乙醛在路易斯酸In(OTf)₃催化作用下发生傅克关环/脱水过程合成多环芳烃(PAHs)的新方法。

背景技术：

多环芳烃(PAHs)在石油工业中广泛存在和应用，而且是很多药物分子的基本骨架。但是由于合成具有高度官能团化以及稠环的多环化合物的方法一直有限，因此受到有机化学家的广泛关注。具有苯并蒽结构的化合物(见下图)一般广泛应用于光学材料以及电子器件中，许多经过修饰的多环芳烃也可以用来

作为半导体材料。更为重要的是，多环芳烃还可以用作潜在的抗癌抗菌药物[(a)Watson,M.D.；A.；Müllen,K.Chem.Rev.2001,101,1267.(b)Anthony,J.E.Chem.Rev.2006,106,5028.(c)Wu,J.；Pisula,W.；Müllen,K.Chem.Rev.2007,107,718.(d)Anthony,J.E.Angew.Chem.Int.Ed.2008,47,452.(d)Feng,X.；Pisula,W.；Müllen,K.Pure Appl.Chem.2009,81,2203；(e)Zhang,H.；Wu,D.；Hua,S.；Liu,H.；Yin,J.Curr.Org.Chem.2012,16,2124.(f)Kuninobu,Y.；Tatsuzaki,T.；Mastuki,T.；Takai,K.J.Org.Chem.2011,76,7005.(g)Segawa,Y.；Stephan,D.W.Chem.Commun.2012,48,11963.(h)Pérez,D.；D.；Guitián,E.Eur.J.Org.Chem.2013,5981.(i)Yu,J.；Yan,H.；Zhu,C.Angew.Chem.Int.Ed.2016,55,1143.(j)Dorel,R.；McGonigal,P.R.；Echavarren,A.M.Angew.Chem.Int.Ed.2016,55,11120.]。其中，当上述多环芳烃具有其他可以进一步官能团化的基团，这类化合物尤其受到人们的关注，因为此类化合物可以进一步转化成更为复杂的多环芳烃，也可以定向向一些具有药物或者生物活性的多环芳烃分子转化。苯并蒽作为其中的一种多环芳烃，也有重要的药学价值，比如以下2种化合物就具有抗癌活性[(a)Y.Zheng,C.Evelyn,WO 2016077793,2016.(b)J.N.Varghese,R.J.Simpson,R.L.Moritz,M.Lou,H.Ji,K.M.Branson,B.J.Smith,WO 2003025017,2003]。

目前关于合成多环芳烃的方法在文献中报导得并不多，大部分的合成都是基于分子内或者分子间的环化，其包括氧化光环化、Diels-Alder反应、过渡金属偶联或者环加成反应[(a)Floyd,A.J.；Dyke,S.F.；Ward,S.E.Chem.Rev.1976,76,509.(b)Pérez,D.；Guitián,E.Chem.Soc.Rev.2004,33,274.(c)Harvey,R.G.Curr.Org.Chem.2004,8,303.]。但是，这些传统的合成方法存在其不可跨越的局限性：底物合成一般都是经过多步合成，原料利用率低，而且过程繁琐，条件苛刻；其次，底物局限性与产物多样性有限：一般经过多步合成的底物对官能团的兼容性比较差，比较敏感的官能团如硝基，氰基，酯基难以适应多步合成方法，从而导致产物的多样性受到限制。另外，应用芳炔的环加成反应也可以合成多环芳烃，但是由于芳炔的活性太高，导致副反应增多，反应效率低，应用于合成工业上的价值并不大[(a)Tadross,P.M.；Stoltz,B.M.Chem.Rev.2012,112,3550.(b)Gampe,C.M.；Carreira,E.M.Angew.Chem.Int.Ed.2012,51,3766.(c)Pérez,D.；D.；Guitián,E.Eur.J.Org.Chem.2013,5981.]。

技术实现要素：

本发明要解决的问题是提供一种多环芳烃化合物；

本发明还提供一种合成多环芳烃的方法，即采用非常简便的方法合成多取代的苯并蒽类衍生物；

本发明的另外一个目的是利用上述多环芳烃化合物用于制备药物。其中R¹，R²和R³可以为各种活性基团或者氢原子，这为进一步转化成更为复杂的多环芳烃或者药物活性分子提供了可能。

本发明提供了一种多环芳烃化合物，该化合物是具有如下结构通式的苯并蒽衍生物：

式中，R¹为H、杂芳基或C₁-C₁₀的烷基；

R²为各种各样的吸电子基团或给电子基团。如，R²可以为CF₃、CH₃SO₂、CH₃CH₂SO₂、PhCH₂OCO、C₁～C₁₀烷氧基、OH、Me₂NCH₂CH₂O、Et₂NCH₂CH₂O,、NH₂、芳基、杂芳基、C₁-C₁₀烷基；。

R³为氢、卤素、芳基、C₁-C₁₀的烷基、C₁-C₁₀的烷氧基、或者苯并芳基等。

上述的芳基为苯基、单取代或多取代的苯基，或萘基。苯基上的取代基可以是氢、C₁-C₁₀烷基、C₁-C₁₀烷氧基、卤素[F、Cl、Br或I]等，优选氢、C₁-C₁₀烷基、C₁-C₁₀烷氧基等；

上述的杂芳基为呋喃环、吡啶环或者噻吩环；

其中，当R¹为H、R³为H时，R²不等于Ph。

推荐如下多环芳烃类衍生物：

所述的多环芳烃类化合物也可以进一步描述具有如下结构式：

其中，R¹、R²和R³的定义如前所述。

本发明还提供了一种非常简便的方法合成上述的苯并蒽类衍生物,该方法包括R¹为H、R³为H时，R²等于Ph的化合物。

本发明方法中，在底物3-芳基-2-萘乙醛中，只需要加入路易斯酸催化剂如In(OTf)₃，Sc(OTf)₃，FeCl₃或[ReBr(CO)₃(thf)]₂，将反应混合物直接加热到30-80℃(R³为苯并芳基时，推荐加热到80℃)，对所考察的底物都以良好到优异的收率得到了相应的多取代的苯并蒽类衍生物。

具体的说本发明的方法如下：

在有机溶剂中和30-80℃下，底物3-芳基-2-萘乙醛和路易斯酸催化剂反应1-2小时获得；

所述的3-芳基-2-萘乙醛和路易斯酸催化剂的摩尔比为1:0.025-0.020；

所述的路易斯酸催化剂是In(OTf)₃，Sc(OTf)₃，FeCl₃或[ReBr(CO)₃(thf)]₂；

所述的3-芳基-2-萘乙醛具有如下的结构式：

所述的多环芳烃化合物具有如下结构式的苯并蒽衍生物：

式中，R¹为H、杂芳基或C₁-C₁₀的烷基；

R²为吸电子基团或给电子基团：CF₃、CH₃SO₂、CH₃CH₂SO₂、PhCH₂OCO、C₁～C₆烷氧基、OH、Me₂NCH₂CH₂O、Et₂NCH₂CH₂O,、NH₂、芳基、杂芳基、C₁-C₁₀烷基；

R³为氢、卤素、芳基、C₁-C₁₀的烷基、C₁-C₁₀的烷氧基、或者苯并芳基；

上述的芳基为苯基、单取代或多取代的苯基，或萘基；苯基上的取代基可以是氢、C₁-C₁₀烷基、C₁-C₁₀烷氧基、卤素；优选氢、C₁-C₁₀烷基、C₁-C₁₀烷氧基；

上述的杂芳基为呋喃基、吡啶基或者噻吩基。

本发明方法中所述的3-芳基-2-萘乙醛化合物的结构式可以如下：

所述的多环芳烃化合物的结构式可以如下：

采用本发明的方法实例子：在有机溶剂中，3-芳基-2-萘乙醛(1个当量)与催化量(2.5-20mol％)的路易斯酸催化剂(所述的路易斯酸催化剂推荐用In(OTf)₃、[ReBr(CO)₃(thf)]₂)在加热条件下，如30-80℃，推荐在40-60℃，反应1-2小时，得到本发明的苯并蒽类衍生物。所述的有机溶剂推荐用二氯甲烷、二氯乙烷、二氧六环、苯、甲苯、二甲苯、乙腈、二甲基亚砜、二甲基甲酰胺。

反应式如下：

R¹、R²和R³如前所述。

采用本发明的方法，首先用3-苯基-2-萘乙醛(1a)为底物，考察了催化剂、温度和时间对这个反应的影响。

表格一 催化剂、温度以及反应时间对反应的影响

^a0.2mmol 1a和xmol％催化剂在2mL二氯乙烷中加热90/120分钟.^b分离收率.

从上述表格中可以发现，反应效果最好的溶剂为二氯乙烷、反应温度为50℃，反应时间为2小时，能以89％的分离收率得到苯并蒽化合物2a。产物的2a结构是通过¹H-NMR，¹³C-NMR，红外，质谱确定的。其中，化合物2a、2b的结构由X-ray单晶衍射进一步确认。

以下的实施例中就应用直接加热到50℃的方法，催化剂选用5mol％的路易斯酸催化剂In(OTf)₃以及反应时间定为2小时，对反应的溶剂效应进行了考察。选用3-苯基-2-萘乙醛(1a)为底物，对一些常见溶剂进行考察，其中的一部分结果如下所示：

表格2溶剂效应对反应的影响

^a0.2mmol1a和5mol％In(OTf)₃在2mL溶剂中加热到50℃反应120分钟.^b分离收率.

从上述表格可以发现，在所考察的各种溶剂中，这个反应都能顺利进行，得到苯并蒽类化合物。而最好两个溶剂是二氯乙烷和甲苯。

接下去对含各种取代基的底物1进行的普适性考察，结果如下表所示：

表格3对底物适用性的考察^a，b

^a0.2mmol 1和5mol％的催化剂In(OTf)₃在2mL溶剂二氯乙烷中加热到50℃反应2小时.^b分离收率.

从表3中可以发现：当R¹、R²和R³为吸电子取代和推电子取代基反应都可以顺利的进行反应，取得理想的效果；当R¹取代的苯环变为噻吩环时，该反应也同样能顺利地得到目标产物。

从上述结果同时可以看出，这个反应对考察的绝大部分2-萘乙醛都适应，在优化的条件下都可以顺利的得到相应的多取代的苯并蒽类衍生物。

将萘乙醛底物进一步拓展到3-苯基-2-蒽乙醛底物1l和3-萘基-2-萘乙醛底物1m，反应也能顺利进行，生成相应的五并环多环芳烃2l和2m，只是反应温度要相应的提高到80℃。

产物2h可以和吗啉在Buchwald-Hartwig氨基化反应条件下实现偶联，生成的偶联产物具有抗癌抗菌性能[Zheng,Y.；Evelyn,C.WO Patent 2016077793,2016]。

本发明是一种非常简单易行的、环境友好的用来制备多环芳烃苯并蒽衍生物的方法。此类产物中可以方便地引入各种活性官能团，这些官能团化的多环芳烃可以进一步转化成更加复杂的多环化合物，也可以进一步转化为一些具有药理活性的多环分子，可以用于制备抗癌抗菌的药物，具有潜在的应用价值和商业用途。

附图说明

图1与图2分别是由X-ray单晶衍射获得的化合物2a和2b的结构图。

具体实施方式

通过以下实施例有助于理解本发明，但并不限制于本发明的内容。

实施例1---化合物2的合成的一般操作步骤

多环芳烃苯并[α]蒽2合成：在25mL干净反应管中，加入3-芳基-2-萘乙醛(1，0.20mmol)，路易斯酸In(OTf)₃(0.01mmol)，在DCE(二氯乙烷)中加热到50℃反应2小时。快速柱层析(SiO₂,洗脱剂为石油醚)得到相应的产物2。

Compound 2a:54mg,89％,白色固体，熔点：189-191℃；IR(CH₂Cl₂):ν2955,2922,2851,1663,1495,1469,1453,1411,1360,1224,1031,821,747,702cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ7.39-7.44(m,3H),7.47(s,2H),7.51-7.61(m,5H),7.64-7.80(m,2H),7.79(dd,1H,J₁＝7.6Hz,J₂＝0.8Hz),8.15(d,1H,J＝8.0Hz),8.87(d,1H,J＝8.4Hz),9.24(s,1H)；¹³C NMR(100MHz,CDCl₃,TMS):δ121.6,123.0,125.5,125.6,125.7,126.7,126.8,126.9,127.1,127.4,128.4,128.47,128.51,128.56,128.63,130.4,130.8,131.2,131.47,131.52,137.5,138.9；MS(ESI)m/z:305.1(M+H⁺,100)；HRMS(ESI)计算值Calcd.for C₂₄H₁₇⁺requires:305.1325,实测值Found:305.1326.

Compound 2b:56mg,88％,白色固体，熔点：194-196℃；IR(CH₂Cl₂):ν2959,2923,2853,1251,1228,1177,1030,825,669cm^-1；¹H NMR(400MHz,CD₂Cl₂,TMS):δ2.55(s,3H),7.38-7.44(m,5H),7.52-7.63(m,7H),8.16(d,1H,J＝8.4Hz),8.77(d,1H,J＝8.4Hz),9.22(s,1H)；¹³C NMR(100MHz,CD₂Cl₂,TMS):δ21.2,121.2,123.0,125.49,125.52,125.6,126.6,126.8,127.5,128.1,128.3,128.4,128.50,128.52,128.6,130.7,131.2,131.6,131.7,137.3,137.5,139.0；MS(ESI)m/z:319.1(M+H⁺,100)；HRMS(ESI)Calcd.for C₂₅H₁₉⁺requires:319.1481,Found:319.1486.

Compound 2c:55mg,86％,白色固体，熔点：190-192℃；IR(CH₂Cl₂):ν2961,2932,2853,1252,1229,1178,1032,826,700cm^-1；¹H NMR(400MHz,CD₂Cl₂,TMS):δ2.54(s,3H),7.36(d,1H,J＝7.2Hz),7.35-7.42(m,4H),7.53-7.64(m,7H),8.14(d,1H,J＝8.0Hz),8.78(d,1H,J＝8.0Hz),9.20(s,1H)；¹³C NMR(100MHz,CD₂Cl₂,TMS):δ21.4,121.0,123.2,125.4,125.5,125.6,126.7,126.8,128.0,128.1,128.2,128.3,128.4,128.5,128.6,130.7,131.3,131.5,131.8,137.6,137.8,139.2；MS(ESI)m/z:319.1(M+H⁺,100)；HRMS(ESI)Calcd.for C₂₅H₁₉⁺requires:319.1481,Found:319.1485.

Compound 2d:61mg,84％,白色固体，熔点：197-199℃；IR(CH₂Cl₂):ν2958,2923,2868,1362,1263,1021,882,845,821,805,768,747cm^-1；¹H NMR(400MHz,CD₂Cl₂,TMS):δ1.47(s,9H),7.35(d,2H,J＝8.0Hz),7.41(t,1H,J＝7.6Hz),7.47(d,1H,J＝9.2Hz),7.51-7.54(m,2H),7.57-7.61(m,3H),7.66-7.71(m,2H),7.79(d,1H,J＝7.2Hz),8.14(d,1H,J＝8.4Hz),8.88(d,1H,J＝8.0Hz),9.23(s,1H)；¹³C NMR(100MHz,CD₂Cl₂,TMS):δ31.5,34.7,121.4,123.1,125.2,125.4,125.6,125.8,126.7,126.8,126.9,127.1,128.45,128.53,128.8,130.5,130.8,131.0,131.5,131.6,135.7,137.7,150.2；MS(ESI)m/z:361.2(M+H⁺,100)；HRMS(ESI)Calcd.for C₂₈H₂₅⁺requires:361.1951,Found:361.1953.

Compound 2e:54mg,84％,白色固体，10:1的异构体，熔点：190-192℃；IR(CH₂Cl₂):ν3053,3028,2914,1617,1597,1508,1442,1073,1019,878,845,836,782,752,742,700,686cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ2.65(s,3H),2.68(s,0.3H),7.38-7.46(m,6.6H),7.50-7.59(m,4.4H),7.64(d,1.1H,J＝8.4Hz),7.68(d,1.1H,J＝8.0Hz),8.15(d,1H,J＝8.4Hz),8.23(d,0.1H,J＝8.4Hz),8.67(s,1H),8.77(d,0.1H,J＝8.0Hz),9.23(s,1H),9.25(s,0.1H)；¹³C NMR(100MHz,CDCl₃,TMS):δ22.2,121.5,123.1,124.6,125.3,125.6,126.6,126.7,127.4,128.32,128.35,128.4,128.5,128.6,128.8,129.3,130.4,130.8,131.2,131.4,136.6,139.0；MS(ESI)m/z:319.1(M+H⁺,100)；HRMS(ESI)Calcd.for C₂₅H₁₉⁺requires:319.1481,Found:319.1487.

Compound 2f:58mg,94％,白色固体，熔点：184-186℃；IR(CH₂Cl₂):ν2917,2847,1662,1597,1448,1418,1317,1242,929,882,815,757,701cm^-1；¹H NMR(400MHz,CD₂Cl₂,TMS):δ7.37(td,1H,J₁＝7.2Hz,J₂＝0.8Hz),7.43(dd,1H,J₁＝8.4Hz,J₂＝1.6Hz),7.49-7.56(m,3H),7.58-7.61(m,3H),7.65-7.69(m,2H),8.11(d,1H,J＝8.4Hz),8.18(d,1H,J＝5.2Hz),8.91(s,1H)；¹³C NMR(100MHz,CD₂Cl₂,TMS):δ120.3,121.8,122.8,124.0,125.2,125.5,125.6,126.9,127.47,127.55,128.1,128.2,128.4,131.1,131.5,135.5,136.5,137.9,139.1；MS(ESI)m/z:311.1(M+H⁺,100)；HRMS(ESI)Calcd.for C₂₂H₁₅S⁺requires:311.0889,Found:311.0892.

Compound 2g:69mg,94％,白色固体，熔点：187-189℃；IR(CH₂Cl₂):ν2959,2922,2850,1652,1635,1470,1076,1021,875,824,745,701cm^-1；¹H NMR(400MHz,CD₂Cl₂,TMS):δ7.26(d,2H,J＝8.0Hz),7.40-7.43(m,2H),7.50(d,1H,J＝8.4Hz),7.54(td,1H,J₁＝8.0Hz,J₂＝0.8Hz),7.56-7.60(m,2H),7.66-7.72(m,3H),7.80(d,1H,J＝7.6Hz),8.13(d,1H,J＝8.0Hz),8.86(d,1H,J＝8.0Hz),9.23(s,1H)；¹³C NMR(100MHz,CD₂Cl₂,TMS):δ121.7,121.9,123.0,125.1,125.6,126.0,126.3,127.0,127.19,127.23,128.47,128.52,128.53,128.7,130.3,130.6,131.39,131.42,131.6,132.9,135.9,137.8；MS(ESI)m/z:339.1(M+H⁺,100)；HRMS(ESI)Calcd.for C₂₄H₁₆Cl⁺requires:339.0936,Found:339.0938.

Compound 2h:69mg,90％,白色固体，熔点：185-187℃；IR(CH₂Cl₂):ν2958,2920,2851,1654,1633,1469,1075,1019,873,822,742,700cm^-1；¹H NMR(400MHz,CD₂Cl₂,TMS):δ7.28(d,2H,J＝8.4Hz),7.40-7.44(m,2H),7.49(d,1H,J＝8.8Hz),7.53(td,1H,J₁＝8.0Hz,J₂＝1.2Hz),7.58-7.62(m,2H),7.66-7.71(m,3H),7.79(d,1H,J＝7.6Hz),8.14(d,1H,J＝8.0Hz),8.86(d,1H,J＝8.0Hz),9.23(s,1H)；¹³C NMR(100MHz,CD₂Cl₂,TMS):δ121.7,121.9,123.0,125.1,125.6,126.0,126.3,127.0,127.19,127.23,128.47,128.52,128.53,128.7,130.3,130.6,131.39,131.42,131.6,132.9,135.9,137.8；MS(ESI)m/z:383.0(M+H⁺,100)；HRMS(ESI)Calcd.for C₂₄H₁₆Br⁺requires:383.0430,Found:383.0435.

Compound 2i:59mg,93％,白色固体，熔点：193-195℃；IR(CH₂Cl₂):ν2961,2924,2852,1252,1229,1179,1032,826,670cm^-1；¹H NMR(400MHz,CD₂Cl₂,TMS):δ2.53(s,3H),7.35-7.43(m,5H),7.51-7.62(m,7H),8.17(d,1H,J＝8.0Hz),8.76(d,1H,J＝8.0Hz),9.21(s,1H)；¹³C NMR(100MHz,CD₂Cl₂,TMS):δ21.3,121.1,123.2,125.5,125.62,125.64,126.7,126.8,127.6,128.2,128.3,128.4,128.5,128.6,128.8,130.9,131.2,131.6,131.8,137.2,137.4,139.0；MS(ESI)m/z:319.1(M+H⁺,100)；HRMS(ESI)Calcd.for C₂₅H₁₉⁺requires:319.1481,Found:319.1484.

Compound 2j:61mg,91％,白色固体，熔点：190-192℃；IR(CH₂Cl₂):ν2955,2921,2851,1626,1506,1464,1423,1266,1227,1168,1033,880,844,821,744,703cm^-1；¹H NMR(400MHz,CD₂Cl₂,TMS):δ3.68(s,3H),6.84(s,1H),7.20(dd,1H,J₁＝8.8Hz,J₂＝2.0Hz),7.40-7.50(m,4H),7.52-7.58(m,4H),7.64(t,1H,J＝7.6Hz),7.76(d,1H,J＝7.6Hz),8.01(d,1H,J＝9.2Hz),8.80(d,1H,J＝8.4Hz),9.13(s,1H)；¹³C NMR(100MHz,CD₂Cl₂,TMS):δ55.0,103.5,119.5,121.4,122.7,125.4,126.6,126.7,126.8,126.9,127.4,127.7,128.4,128.5,129.0,130.2,130.6,131.10,131.14,131.9,135.8,139.2,157.4；MS(ESI)m/z:335.1(M+H⁺,100)；HRMS(ESI)Calcd.for C₂₅H₁₉O⁺requires:335.1430,Found:335.1428.

Compound 2k:73mg,92％,白色固体，熔点：205-207℃；IR(CH₂Cl₂):ν3042,2963,2864,1498,1465,1351,1201,1110,1076,958,946,872,843,823,742,699cm^-1；¹H NMR(400MHz,CD₂Cl₂,TMS):δ1.47(s,9H),7.30(d,2H,J＝8.4Hz),7.44(dd,1H,J₁＝8.8Hz,J₂＝2.0Hz),7.49(brs,2H),7.57-7.62(m,3H),7.66-7.70(m,2H),7.79(d,1H,J＝7.6Hz),8.05(d,1H,J＝8.8Hz),8.83(d,1H,J＝8.4Hz),9.17(s,1H)；¹³C NMR(100MHz,CD₂Cl₂,TMS):δ31.5,34.7,121.4,123.0,125.3,125.4,125.6,126.5,127.0,127.30,127.32,128.5,128.7,129.5,129.6,130.2,130.3,130.7,131.4,131.47,131.55,134.9,137.0,150.5；MS(ESI)m/z:395.2(M+H⁺,100)；HRMS(ESI)Calcd.for C₂₈H₂₄Cl⁺requires:395.1561,Found:395.1570.

产物2l:38mg,53％,白色固体，熔点:220-222℃.IR(CH₂Cl₂):ν3050,2923,2848,1660,1494,1455,1441,893,818,786,765,735,702cm^-1；¹H NMR(400MHz,CD₂Cl₂,TMS):δ7.36-7.46(m,4H),7.50(dd,2H,J₁＝7.6Hz,J₂＝2.0Hz),7.57-7.70(m,5H),7.75(d,1H,J＝8.4Hz),7.85(d,1H,J＝8.4Hz),8.06(d,1H,J＝8.4Hz),8.23(s,1H),8.77(s,1H),8.88(d,1H,J＝8.4Hz),9.40(s,1H)；¹³C NMR(100MHz,CD₂Cl₂,TMS):δ121.8,123.1,125.2,125.4,125.5,125.8,126.8,127.0,127.1,127.4,127.6,127.9,128.4,128.48,128.51,128.7,129.9,130.0,130.6,131.3,131.4,131.55,131.57,137.1,139.1；MS(ESI)m/z:355.1(M+H⁺,100)；HRMS(ESI)Calcd.for C₂₈H₁₉⁺requires:355.1481,Found:355.1478.

产物2m.43mg,67％,白色固体，熔点:212-214℃.IR(CH₂Cl₂):ν3051,2956,2920,2848,1599,1505,1469,1435,1158,1016,833,773,749,702cm^-1；¹H NMR(400MHz,CD₂Cl₂,TMS):δ7.23-7.50(m,3H),7.54-7.66(m,7H),7.71-7.74(m,2H),7.76(d,1H,J＝8.4Hz),7.93(d,1H,J＝8.4Hz),8.04(d,1H,J＝8.4Hz),8.17(d,1H,J＝8.4Hz),9.28(d,1H,J＝8.4Hz),9.66(s,1H)；¹³C NMR(100MHz,CD₂Cl₂,TMS):δ125.4,125.7,125.8,126.1,126.45,126.50,126.7,126.8,127.2,127.5,127.7,127.9,128.3,128.4,128.69,128.73,130.0,130.2,130.3,130.6,131.1,131.4,133.7,136.8,139.1；MS(ESI)m/z:355.1(M+H⁺,100)；HRMS(ESI)Calcd.for C₂₈H₁₉⁺requires:355.1481,Found:355.1481。

实施例2---化合物3的合成

抗癌试剂3的合成：在充满氩气的25mL干净反应管中，加入多环芳烃2h(0.2mmol)，催化剂Pd₂(dba)₃(0.01mmol),配体XantPhos(4,5-双二苯基膦-9,9-二甲基氧杂蒽,0.02mmol),碱Cs₂CO₃(0.4mmol),吗啉(0.4mmol),在甲苯中加热到100℃，反应4小时。快速柱层析(SiO₂,洗脱剂为石油醚/乙酸乙酯＝10/1)得到相应的产物3。

Compound 3:49mg,63％,白色固体，熔点:218-220℃；IR(CH₂Cl₂):ν2962,2919,2848,2820,1645,1607,1515,1502,1446,1257,1234,1122,928,831,822,803,770,751cm^-1；¹H NMR(400MHz,CD₂Cl₂,TMS):δ3.03(t,4H,J＝4.0Hz),3.94(t,4H,J＝4.0Hz),7.09(d,2H,J＝7.6Hz),7.33(d,2H,J＝8.4Hz),7.42(t,1H,J＝7.6Hz),7.54(t,1H,J＝7.6Hz),7.58-7.62(m,3H),7.68(d,1H,J＝8.0Hz),7.73(t,1H,J＝8.4Hz),7.81(d,1H,J＝8.0Hz),8.15(d,1H,J＝8.4Hz),8.89(d,1H,J＝8.4Hz),9.23(s,1H)；¹³C NMR(100MHz,CD₂Cl₂,TMS):δ49.1,67.0,115.2,121.3,123.1,125.4,125.6,125.8,126.6,126.83,126.84,127.1,128.4,128.6,129.0,130.0,130.5,131.2,131.5,131.6,132.0,137.5,150.3；MS(ESI)m/z:390.2(M+H⁺,100)；HRMS(ESI)Calcd.for C₂₈H₂₄NO⁺requires:390.1852,Found:390.1854。

实施例3化合物1的合成

反应式如下：

3-芳基-2-萘乙醛1合成：在充满氩气的干净反应管中，加入亚甲基环丙烷取代的1,5-烯炔(1，0.20mmol)，3,5-二溴吡啶氮氧化合物(0.3mmol)，金催化剂JohnPhosAu(NCMe)SbF₆(0.01mmol)，在甲苯中加热到95℃反应4小时。快速柱层析(SiO₂,洗脱剂为石油醚/乙酸乙酯＝25:1)得到相应的产物1。R¹、R²和R³同前所述。

Compound 1a(R¹＝Ph,R²＝Ph,R³＝H):59mg,92％,白色固体,熔点：143-145℃；IR(CH₂Cl₂):ν3055,2954,2923,2826,1722,1488,1442,1382,1109,1028,892,751,703cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ3.63(s,2H),7.26(d,2H,J＝7.2Hz),7.33-7.40(m,4H),7.42-7.49(m,7H),7.80(s,1H),7.85(d,1H,J＝8.4Hz),9.41(s,1H)；¹³C NMR(100MHz,CDCl₃,TMS):δ47.1,126.10,126.13,126.6,127.2,127.4,127.6,127.8,128.3,128.58,128.61,129.3,130.0,132.3,139.2,140.7,140.8,141.5,199.7；MS(ESI)m/z:323.1(M+H⁺,100)；HRMS(ESI)计算值Calcd.for C₂₄H₁₉O⁺实测值requires:323.1430,Found:323.1442.

Compound 1b(R¹＝4-Me-Ph,R²＝Ph,R³＝H):58mg,86％,白色固体，熔点：149-151℃；IR(CH₂Cl₂):ν3054,3020,2922,2852,1777,1723,1594,1512,1442,1382,1109,1023,819,750,704cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ2.39(s,3H),3.63(s,2H),7.19-7.26(m,6H),7.30-7.34(m,2H),7.39-7.48(m,4H),7.78(s,1H),7.83(d,1H,J＝8.0Hz),9.40(s,1H)；¹³C NMR(100MHz,CDCl₃,TMS):δ21.2,47.1,126.00,126.04,126.6,127.4,127.6,127.7,128.5,128.6,129.0,129.2,130.0,132.2,132.3,137.0,138.5,139.2,140.6,140.8,199.8；MS(ESI)m/z:319.1(M+H⁺-H₂O,100)；HRMS(ESI)Calcd.for C₂₅H₁₉⁺requires:319.1481,Found:319.1495.

Compound 1c(R¹＝4-OMe-Ph,R²＝Ph,R³＝H):61mg,87％,白色固体，熔点：153-155℃；IR(CH₂Cl₂):ν3059,2954,2922,2848,1772,1720,1608,1512,1286,1247,1176,1031,832,752,704cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ3.64(s,2H),3.84(s,3H),6.95(d,2H,J＝8.8Hz),7.24-7.27(m,4H),7.34(d,2H,J＝4.0Hz),7.43-7.49(m,4H),7.79(s,1H),7.84(d,1H,J＝8.0Hz),9.42(s,1H)；¹³C NMR(100MHz,CDCl₃,TMS):δ47.1,55.3,113.7,126.0,126.1,126.6,127.58,127.63,127.7,128.6,128.8,130.0,130.4,132.2,132.4,133.8,139.3,140.5,140.6,158.9,199.8；MS(ESI)m/z:335.1(M+H⁺-H₂O,100)；HRMS(ESI)Calcd.for C₂₅H₁₉O⁺requires:335.1430,Found:335.1440.

Compound 1d(R¹＝4-Cl-Ph,R²＝Ph,R³＝H):61mg,85％,白色固体，熔点：156-158℃；IR(CH₂Cl₂):ν2956,2922,2851,1722,1714,1488,1385,1087,1015,894,831,824,758,746,705cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ3.61(s,2H),7.24-7.29(m,4H),7.35-7.40(m,4H),7.44-7.50(m,4H),7.76(s,1H),7.85(d,1H,J＝8.0Hz),9.42(s,1H)；¹³C NMR(100MHz,CDCl₃,TMS):δ47.1,126.27,126.30,126.7,127.0,127.7,127.8,128.5,128.62,128.65,129.9,130.7,132.3,132.4,133.6,139.1,139.6,140.0,140.9,199.5；MS(ESI)m/z:339.1(M+H⁺-H₂O,100)；HRMS(ESI)Calcd.for C₂₄H₁₆Cl⁺requires:339.0935,Found:339.0946.

Compound 1e(R¹＝3-Me-Ph,R²＝Ph,R³＝H):60mg,90％,白色固体，熔点：144-146℃；IR(CH₂Cl₂):ν3056,2956,2915,2868,1708,1598,1484,1382,1299,1261,1093,1018,800,787,748,702cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ2.40(s,3H),3.63(s,2H),7.12-7.20(m,3H),7.24-7.27(m,3H),7.30-7.36(m,2H),7.43-7.50(m,4H),7.80(s,1H),7.85(d,1H,J＝8.0Hz),9.42(s,1H)；¹³C NMR(100MHz,CDCl₃,TMS):δ21.4,47.0,126.00,126.04,126.3,126.6,127.3,127.6,127.7,128.08,128.11,128.51,128.54,129.98,130.01,132.2,132.3,137.9,139.2,140.7,141.0,141.4,199.7；MS(ESI)m/z:319.1(M+H⁺-H₂O,100)；HRMS(ESI)Calcd.for C₂₅H₁₉⁺requires:319.1481,Found:319.1496.

Compound 1f(R¹＝3-F-Ph,R²＝Ph,R³＝H):55mg,81％,白色固体，熔点：145-147℃；IR(CH₂Cl₂):ν3059,2967,2815,2718,1720,1611,1580,1486,1442,1263,1028,878,789,749,701cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ3.63(s,2H),7.06-7.12(m,3H),7.24-7.26(m,2H),7.34-7.40(m,3H),7.44-7.50(m,4H),7.79(s,1H),7.86(d,1H,J＝8.0Hz),9.42(s,1H)；¹³C NMR(100MHz,CDCl₃,TMS):δ47.0,114.4(d,J_C-F＝20.8Hz),116.4(d,J_C-F＝21.6Hz),125.2(d,J_C-F＝3.0Hz),126.27,126.33,126.6,126.9,127.7(d,J_C-F＝8.2Hz),128.57,128.61,129.8(d,J_C-F＝8.2Hz),129.9,132.2,132.5,139.0,139.5(d,J_C-F＝2.2Hz),140.9,143.6,143.7,162.4(d,J_C-F＝245.6Hz),199.4；¹⁹F NMR(376MHz,CDCl₃,CFCl₃):δ-112.7(ddd,1F,J₁＝14.7Hz,J₂＝9.0Hz,J₃＝5.6Hz)；MS(ESI)m/z:341.1(M+H⁺,100)；HRMS(ESI)Calcd.for C₂₄H₁₈FO⁺requires:341.1336,Found:341.1352.

Compound 1g(R¹＝2-Me-Ph,R²＝Ph,R³＝H):57mg,85％,白色固体，熔点：142-144℃；IR(CH₂Cl₂):ν3054,2974,2895,1721,1487,1442,1381,1087,1045,880,751,732,704cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ2.10(s,3H),3.38(d,1H,J＝17.6Hz),3.55(d,1H,J＝17.6Hz),7.16-7.29(m,6H),7.33(d,1H,J＝7.6Hz),7.36-7.47(m,5H),7.71(s,1H),7.83(d,1H,J＝8.4Hz),9.30(s,1H)；¹³C NMR(100MHz,CDCl₃,TMS):δ20.1,46.7,125.6,126.0,126.6,127.6,127.7,127.8,128.1,128.5,128.6,129.8,129.9,130.0,130.1,132.3,132.4,135.8,139.0,140.0,140.6,140.8,199.0；MS(ESI)m/z:319.1(M+H⁺-H₂O,100)；HRMS(ESI)Calcd.for C₂₅H₁₉⁺requires:319.1481,Found:319.1494.

Compound 1h(R¹＝cyclopropyl,R²＝Ph,R³＝H):61mg,84％,白色固体，熔点：132-134℃；IR(CH₂Cl₂):ν3056,3001,2930,2832,1719,1489,1386,1208,1043,1025,920,890,750,703cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ0.75-0.79(m,2H),0.95-0.99(m,2H),1.87-1.93(m,1H),3.89(s,2H),7.21-7.22(m,2H),7.24-7.30(m,2H),7.38-7.49(m,4H),7.61(s,1H),7.78(d,1H,J＝8.0Hz),9.67(s,1H)；¹³C NMR(100MHz,CDCl₃,TMS):δ7.0,14.8,46.3,125.3,125.5,125.8,126.5,127.4,127.5,128.6,129.4,129.9,131.7,132.7,139.4,139.5,140.4,200.0；MS(ESI)m/z:287.1(M+H⁺,100)；HRMS(ESI)Calcd.for C₂₁H₁₉O⁺requires:287.1430,Found:287.1432.

Compound 1i(R¹＝ⁿbutyl,R²＝Ph,R³＝H):57mg,76％,白色固体，熔点：138-140℃；IR(CH₂Cl₂):ν3051,2955,2928,2870,1720,1490,1442,1380,1027,883,749,703cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ0.98(t,3H,J＝7.6Hz),1.43-1.49(m,2H),1.63-1.71(m,2H),2.71(t,2H,J＝7.6Hz),3.72(s,2H),7.21-7.22(m,2H),7.27-7.28(m,2H),7.41-7.49(m,4H),7.73(s,1H),7.80(d,1H,J＝8.4Hz),9.61(s,1H)；¹³C NMR(100MHz,CDCl₃,TMS):δ14.0,22.7,32.8,33.5,46.0,125.3,125.8,126.5,127.22,127.23,127.5,128.6,130.0,131.6,132.8,139.2,139.6,140.7,199.9；MS(ESI)m/z:303.2(M+H⁺,100)；HRMS(ESI)Calcd.for C₂₂H₂₃O⁺requires:303.1743,Found:303.1738.

Compound 1j(R¹＝thienyl,R²＝Ph,R³＝H):54mg,83％,白色固体，熔点：146-148℃；IR(CH₂Cl₂):ν3101,3054,2967,2923,1720,1488,1380,1073,1046,1027,895,880,853,790,765,750,703cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ3.66(s,2H),7.10(dd,1H,J₁＝5.2Hz,J₂＝1.2Hz),7.23-7.26(m,3H),7.34-7.35(m,2H),7.38-7.40(m,1H),7.43-7.50(m,4H),7.84-7.86(m,2H),9.46(s,1H)；¹³C NMR(100MHz,CDCl₃,TMS):δ47.2,123.5,125.7,126.1,126.2,126.6,127.6,127.7,128.6,128.9,129.0,129.9,132.3,132.4,135.6,139.2,140.7,141.6,199.8；MS(ESI)m/z:329.1(M+H⁺,100)；HRMS(ESI)Calcd.for C₂₂H₁₇OS⁺requires:329.0994,Found:329.0999.

Compound 1k(R¹＝naphthyl,R²＝Ph,R³＝H):64mg,86％,白色固体，熔点：162-164℃；IR(CH₂Cl₂):ν3051,2926,2829,1720,1446,1393,1381,1110,1018,803,780,751,703cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ3.31(dd,1H,J₁＝18.0Hz,J₂＝0.8Hz),3.46(dd,1H,J₁＝18.0Hz,J₂＝0.8Hz),7.28(dd,1H,J₁＝7.2Hz,J₂＝0.8Hz),7.35-7.53(m,12H),7.84(d,2H,J＝6.8Hz),7.89(t,2H,J＝6.8Hz),9.23(s,1H)；¹³C NMR(100MHz,CDCl₃,TMS):δ46.9,125.3,125.8,126.0,126.17,126.22,126.4,126.7,127.62,127.65,127.8,128.1,128.3,128.4,128.5,128.6,129.4,130.0,130.2,132.2,132.4,132.6,133.5,138.6,138.7,139.0,140.8,199.1；MS(ESI)m/z:355.1(M+H⁺-H₂O,100)；HRMS(ESI)Calcd.for C₂₈H₁₉⁺requires:355.1481,Found:355.1476.

Compound 1l(R¹＝Ph,R²＝3-Me-Ph,R³＝H):58mg,86％,白色固体，熔点：147-149℃；IR(CH₂Cl₂):ν3056,2956,2922,2852,1722,1603,1495,1442,1380,1109,1029,892,763,752,704cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ2.40(s,3H),3.63(s,2H),7.05-7.08(m,2H),7.24(d,1H,J＝7.6Hz),7.32-7.48(m,9H),7.79(s,1H),7.84(d,1H,J＝8.0Hz),9.41(s,1H)；¹³C NMR(100MHz,CDCl₃,TMS):δ21.4,47.0,126.0,126.1,126.7,127.1,127.2,127.4,127.7,128.25,128.32,128.4,128.5,129.3,130.6,132.31,132.33,138.2,139.1,140.8,140.9,141.5,199.7；MS(ESI)m/z:319.1(M+H⁺-H₂O,100)；HRMS(ESI)Calcd.for C₂₅H₁₉⁺requires:319.1481,Found:319.1495.

Compound 1m(R¹＝Ph,R²＝2-Me-Ph,R³＝H):57mg,85％,白色固体，熔点：143-145℃；IR(CH₂Cl₂):ν3056,3020,2923,2823,1722,1494,1484,1443,1380,1109,1027,892,751,729,703cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ1.94(s,3H),3.48(d,1H,J＝17.6Hz),3.66(d,1H,J＝17.6Hz),7.14(d,1H,J＝7.6Hz),7.24(d,1H,J＝8.4Hz),7.27-7.31(m,1H),7.33-7.49(m,9H),7.81(s,1H),7.87(d,1H,J＝8.0Hz),9.36(s,1H)；¹³C NMR(100MHz,CDCl₃,TMS):δ19.7,46.7,126.1,126.2,126.3,127.3,127.4,127.9,128.0,128.28,128.29,128.52,128.54,129.4,130.3,131.8,132.4,136.7,138.4,140.0,141.0,141.5,199.3；MS(ESI)m/z:319.1(M+H⁺-H₂O,100)；HRMS(ESI)Calcd.for C₂₅H₁₉⁺requires:319.1481,Found:319.1477.

Compound 1n’(R¹＝Ph,R²＝4-Me-Ph,R³＝H,醛不稳定，还原成醇):49mg,73％,白色固体，熔点：145-147℃；IR(CH₂Cl₂):ν3054,3023,2923,2876,1513,1491,1467,1380,1036,892,773,750,703cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ1.09(s,1H),2.44(s,3H),2.85(t,2H,J＝7.2Hz),3.30(t,2H,J＝7.2Hz),7.19-7.21(m,2H),7.28-7.42(m,10H),7.69(s,1H),7.78(d,1H,J＝8.0Hz)；¹³C NMR(100MHz,CDCl₃,TMS):δ21.3,34.2,62.5,125.6,125.8,126.6,127.0,127.6,128.1,128.7,129.1,129.4,130.1,131.5,131.7,132.6,136.5,136.8,140.0,140.9,142.1；MS(ESI)m/z:321.2(M+H⁺-H₂O,100)；HRMS(ESI)Calcd.for C₂₅H₂₁⁺requires:321.1638,Found:321.1649.

Compound 1o’(R¹＝Ph,R²＝4-^tBu-Ph,R³＝H,醛不稳定，还原成醇):64mg,84％,白色固体，熔点：154-156℃；IR(CH₂Cl₂):ν3054,2960,2881,1490,1464,1390,1364,1056,1017,899,832,769,744,700cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ1.03(s,1H),1.41(s,9H),2.88(t,2H,J＝7.6Hz),3.34(t,2H,J＝7.6Hz),7.25(d,2H,J＝8.0Hz),7.32(brs,2H),7.37-7.44(m,6H),7.50(d,2H,J＝8.0Hz),7.70(s,1H),7.80(d,1H,J＝8.4Hz)；¹³C NMR(100MHz,CDCl₃,TMS):δ31.5,34.3,34.6,62.6,125.2,125.6,125.8,126.7,127.1,127.6,128.1,128.8,129.4,129.9,131.5,131.7,132.7,136.4,140.1,140.9,142.1,150.0；MS(ESI)m/z:363.2(M+H⁺-H₂O,100)；HRMS(ESI)Calcd.for C₂₈H₂₇⁺requires:363.2107,Found:363.2113.

Compound 1p’(R¹＝Ph,R²＝4-OMe-Ph,R³＝H,醛不稳定，还原成醇):50mg,70％,白色固体，熔点：152-154℃；IR(CH₂Cl₂):ν3054,2954,2923,2851,1608,1513,1491,1462,1285,1245,1175,1031,835,750,704cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ1.14(s,1H),2.87(t,2H,J＝7.6Hz),3.32(t,2H,J＝7.6Hz),3.87(s,3H),7.03(d,2H,J＝8.4Hz),7.24(d,2H,J＝8.4Hz),7.32-7.43(m,8H),7.70(s,1H),7.79(d,1H,J＝8.0Hz)；¹³C NMR(100MHz,CDCl₃,TMS):δ34.3,55.2,62.5,113.8,125.6,125.8,126.6,127.0,127.6,128.1,128.7,129.4,131.3,131.6,131.7,131.8,132.9,139.7,141.0,142.1,158.7；MS(ESI)m/z:337.2(M+H⁺-H₂O,100)；HRMS(ESI)Calcd.for C₂₅H₂₁O⁺requires:337.1587,Found:337.1600.

Compound 1q’(R¹＝Ph,R²＝4-Cl-Ph,R³＝H,醛不稳定，还原成醇):52mg,72％,白色固体，熔点：154-156℃；IR(CH₂Cl₂):ν3059,2967,2873,1495,1487,1381,1088,1039,1016,895,833,777,703cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ1.05(s,1H),2.84(t,2H,J＝7.6Hz),3.31(t,2H,J＝7.6Hz),7.26-7.28(m,3H),7.32-7.45(m,7H),7.48(d,2H,J＝8.0Hz),7.72(s,1H),7.81(d,1H,J＝8.0Hz)；¹³C NMR(100MHz,CDCl₃,TMS):δ34.2,62.4,125.8,126.1,126.2,127.2,127.7,128.2,128.7,129.2,129.4,131.6,131.7,131.8,132.3,133.4,138.0,138.7,140.9,141.8；MS(ESI)m/z:341.1(M+H⁺-H₂O,100)；HRMS(ESI)Calcd.for C₂₄H₁₈Cl⁺requires:341.1092,Found:341.1106.

Compound 1r’(R¹＝Ph,R²＝4-Br-Ph,R³＝H,醛不稳定，还原成醇):64mg,79％,白色固体，熔点：158-160℃；IR(CH₂Cl₂):ν3053,3023,2914,1484,1442,1070,1011,878,835,747,700cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ1.13(s,1H),2.82(t,2H,J＝7.6Hz),3.27(t,2H,J＝7.6Hz),7.20(d,2H,J＝8.4Hz),7.26(d,1H,J＝8.4Hz),7.31(d,1H,J＝7.2Hz),7.34-7.37(m,1H),7.40-7.44(m,5H),7.61(d,2H,J＝8.0Hz),7.71(s,1H),7.79(d,1H,J＝8.4Hz)；¹³C NMR(100MHz,CDCl₃,TMS):δ34.1,62.3,121.5,125.8,126.07,126.14,127.1,127.7,128.2,129.2,129.3,131.5,131.6,131.7,132.0,132.2,138.5,138.6,140.8,141.8；MS(ESI)m/z:385.1(M+H⁺-H₂O,100)；HRMS(ESI)Calcd.for C₂₄H₁₈Br⁺requires:385.0586,Found:385.0589.

Compound 1s’(R¹＝Ph,R²＝4-CF₃-Ph,R³＝H,醛不稳定，还原成醇):60mg,77％,白色固体，熔点：147-149℃；IR(CH₂Cl₂):ν3059,2945,2890,1491,1325,1160,1120,1106,1067,1055,1036,1019,856,750,701cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ1.08(s,1H),2.82(t,2H,J＝7.6Hz),3.30(t,2H,J＝7.6Hz),7.18(d,1H,J＝8.4Hz),7.20-7.48(m,9H),7.75-7.76(m,2H),7.78(s,1H),7.82(d,1H,J＝8.0Hz)；¹³C NMR(100MHz,CDCl₃,TMS):δ34.1,62.3,124.2(q,J_C-F＝270.2Hz),125.4(q,J_C-F＝3.7Hz),125.9,126.0,126.2,127.2,127.8,128.2,129.4,129.5,129.6(q,J_C-F＝32.0Hz),130.8,131.4,131.8,132.0,138.5,140.9,141.7,143.6；¹⁹F NMR(376MHz,CDCl₃,CFCl₃):δ-62.3(s,3F)；MS(ESI)m/z:375.1(M+H⁺-H₂O,100)；HRMS(ESI)Calcd.for C₂₅H₁₈F₃⁺requires:375.1355,Found:375.1365.

Compound 1t(R¹＝Ph,R²＝Me,R³＝H):45mg,87％,白色固体，熔点：129-131℃；IR(CH₂Cl₂):ν3055,2925,2825,2718,1719,1495,1444,1381,1110,1022,888,777,764,747,703cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ2.62(s,3H),3.91(s,2H),7.29(dd,1H,J₁＝7.6Hz,J₁＝1.2Hz),7.39-7.45(m,3H),7.48-7.57(m,2H),7.66(s,1H),7.82(d,1H,J＝7.6Hz),8.09(d,1H,J＝8.0Hz),9.69(s,1H)；¹³C NMR(100MHz,CDCl₃,TMS):δ15.6,46.7,117.2,124.1,126.0,126.2,126.7,127.3,127.4,128.3,128.5,129.3,132.1,132.4,133.9,141.1,142.0,199.5；MS(ESI)m/z:243.1(M+H⁺-H₂O,100)；HRMS(ESI)Calcd.for C₁₉H₁₅⁺requires:243.1168,Found:243.1180.

Compound 1u’(R¹＝Ph,R²＝thienyl,R³＝H,醛不稳定，还原成醇):24mg,36％,白色固体，熔点：150-152℃；IR(CH₂Cl₂):ν3101,3054,2967,2923,1486,1383,1074,1050,1029,896,880,855,766,750,703cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ1.08(s,1H),2.99(t,2H,J＝7.6Hz),3.45(t,2H,J＝7.6Hz),7.07(brs,1H),7.21(t,1H,J＝4.0Hz),7.38-7.51(m,9H),7.75(s,1H)7.81(d,1H,J＝8.0Hz)；¹³C NMR(100MHz,CDCl₃,TMS):δ34.7,63.0,125.9,126.2,126.28,126.33,127.1,127.2,127.6,128.2,128.6,129.4,130.1,131.7,131.9,133.7,134.4,139.8,140.8,141.7；MS(ESI)m/z:313.1(M+H⁺-H₂O,100)；HRMS(ESI)Calcd.for C₂₂H₁₇S⁺requires:313.1045,Found:313.1052.

Compound 1v(R¹＝Ph,R²＝Ph,R³＝5-Cl):62mg,87％,白色固体，熔点：155-157℃；IR(CH₂Cl₂):ν2961,2921,2850,1720,1654,1633,1489,1087,1046,1015,831,824,758,746,704,660cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ3.62(s,2H),7.24(d,2H,J＝7.2Hz),7.31-7.33(m,2H),7.41-7.42(m,4H),7.48-7.50(m,3H),7.77(s,1H),7.79(d,1H,J＝8.8Hz),9.40(s,1H)；¹³C NMR(100MHz,CDCl₃,TMS):δ47.2,125.5,127.1,127.6,128.0,128.35,128.40,128.6,128.8,129.2,129.4,129.9,130.6,132.0,133.0,138.5,140.0,141.1,141.2,199.3；MS(ESI)m/z:339.1(M+H⁺-H₂O,100)；HRMS(ESI)Calcd.for C₂₄H₁₆Cl⁺requires:339.0935,Found:339.0940.

Compound 1w(R¹＝Ph,R²＝Ph,R³＝5-OMe):62mg,88％,白色固体，熔点：151-153℃；IR(CH₂Cl₂):ν3054,2926,2826,2726,1721,1623,1592,1491,1395,1250,1227,1206,1029,890,756,703cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ3.60(s,2H),3.64(s,3H),6.63(s,1H),7.14(dd,1H,J₁＝8.8Hz,J₂＝2.0Hz),7.26(d,2H,J＝6.8Hz),7.31-7.45(m,6H),7.48(d,2H,J＝6.8Hz),7.72(s,1H),7.74(d,2H,J＝8.8Hz),9.40(s,1H)；¹³C NMR(100MHz,CDCl₃,TMS):δ47.1,55.0,105.2,118.5,127.2,127.61,127.62,127.9,128.2,128.3,128.7,129.3,129.4,129.9,133.5,138.6,139.4,139.5,141.6,157.7,199.7；MS(ESI)m/z:335.1(M+H⁺-H₂O,100)；HRMS(ESI)Calcd.for C₂₅H₁₉O⁺requires:335.1430,Found:335.1438.

Compound 1x(R¹＝Ph,R²＝Ph,R³＝4-Cl):61mg,85％,白色固体，熔点：158-160℃；IR(CH₂Cl₂):ν3059,3031,2920,2854,1722,1698,1495,1481,1380,1081,899,826,755,703cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ3.61(s,2H),7.23-7.32(m,6H),7.37-7.50(m,6H),7.71(s,1H),7.83(s,1H),9.40(s,1H)；¹³C NMR(100MHz,CDCl₃,TMS):δ47.1,126.3,126.9,127.6,127.67,127.75,127.9,128.37,128.43,128.7,129.2,129.9,130.6,132.0,133.0,138.7,140.8,141.1,142.1,199.4；MS(ESI)m/z:339.1(M+H⁺-H₂O,100)；HRMS(ESI)Calcd.for C₂₄H₁₆Cl⁺requires:339.0935,Found:339.0939.

Compound 1y(R¹＝Ph,R²＝4-^tBu-Ph,R³＝5-Cl):67mg,81％,白色固体，熔点：165-167℃；IR(CH₂Cl₂):ν2961,2923,2864,1724,1587,1495,1481,1461,1444,1376,1269,1079,959,892,757,703cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ1.40(s,9H),3.62(s,2H),7.15(d,2H,J＝8.0Hz),7.31(d,2H,J＝7.2Hz),7.37-7.43(m,5H),7.49(d,2H,J＝8.8Hz),7.75(s,1H),7.77(d,1H,J＝8.8Hz),9.40(s,1H)；¹³C NMR(100MHz,CDCl₃,TMS):δ31.4,34.7,47.1,125.6,125.7,127.0,127.5,128.25,128.32,128.8,129.2,129.4,129.5,130.6,131.9,133.2,135.2,140.2,141.2,150.8,199.6；MS(ESI)m/z:395.2(M+H⁺-H₂O,100)；HRMS(ESI)Calcd.for C₂₈H₂₄Cl⁺requires:395.1561,Found:395.1573.

Compound 1z(R¹＝Ph,R²＝Ph,R³＝Ph):69mg,93％,白色固体，熔点：171-173℃；IR(CH₂Cl₂):ν3052,3020,2950,2924,1722,1599,1492,1441,1107,1023,901,889,770,744,703cm^-1；¹H NMR(400MHz,CDCl₃,TMS):δ3.65(s,2H),7.32-7.45(m,9H),7.48-7.54(m,3H),7.77(d,1H,J＝8.8Hz),7.89(s,1H),7.94(s,1H),7.97(d,1H,J＝8.8Hz),8.40(s,1H),9.42(s,1H)；¹³C NMR(100MHz,CDCl₃,TMS):δ47.3,125.3,125.67,125.68,126.1,127.0,127.4,127.7,128.3,128.62,128.64,128.7,129.4,130.1,130.6,131.1,131.67,131.72,139.3,140.3,140.6,141.5,199.6；MS(ESI)m/z:373.2(M+H⁺,100)；HRMS(ESI)Calcd.for C₂₈H₂₁O⁺requires:373.1587,Found:373.1585。