N-苯基-3-苯亚甲基异吲哚-1-酮的膦酰化衍生物的制备方法转让专利
申请号 : CN201710692103.2
文献号 : CN107383097B
文献日 : 2019-05-24
发明人 : 曾润生 , 施鹏 , 王清 , 赵应声
申请人 : 苏州大学
摘要 :
本发明涉及一种N‑苯基‑3‑苯亚甲基异吲哚‑1‑酮的膦酰化衍生物的制备方法，包括以下步骤：将式(1)的取代N‑苯基‑3‑苯亚甲基异吲哚‑1‑酮衍生物和式(2)的二苯基氧膦在银盐的催化作用下，在含有硝酸盐的有机溶剂中于0～35℃下反应，得到式(3)的N‑苯基‑3‑苯亚甲基异吲哚‑1‑酮的膦酰化衍生物，以上反应的路线如下：其中，R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11独立地选自氢、烷基、烷氧基、卤素或三氟甲基。本发明的方法可以高收率的得到多种N‑苯基‑3‑苯亚甲基异吲哚‑1‑酮的膦酰化衍生物；反应条件温和、操作和后处理过程简单，适合于规模化生产。
权利要求 :
1.一种N-苯基-3-苯亚甲基异吲哚-1-酮的膦酰化衍生物的制备方法，其特征在于，包括以下步骤：将式(1)的取代N-苯基-3-苯亚甲基异吲哚-1-酮衍生物和式(2)的二苯基氧膦在银盐的催化作用下，在含有硝酸盐的有机溶剂中于0～35℃下反应，得到式(3)的N-苯基-3-苯亚甲基异吲哚-1-酮的膦酰化衍生物，以上反应的路线图如下：其中，R1、R2、R3、R4、R5、R6、R7、R8、R9、R11为氢，R10为氢、烷基、烷氧基、卤素或三氟甲基；
或R1、R2、R3、R4、R5、R6、R7、R8、R10、R11为氢，R9为氢、烷基或卤素；
或R1、R2、R3、R4、R6、R7、R8、R9、R10、R11为氢，R5为氢、烷基、烷氧基或卤素；
或R1、R2、R4、R5、R6、R7、R8、R9、R10、R11为氢，R3为卤素；
或R1、R3、R4、R5、R6、R7、R8、R9、R10、R11为氢，R2为氢、烷基、烷氧基或卤素；
或R2、R3、R4、R5、R6、R7、R8、R9、R10、R11为氢，R1为氢或卤素。
2.根据权利要求1所述的N-苯基-3-苯亚甲基异吲哚-1-酮的膦酰化衍生物的制备方法，其特征在于：所述烷基为甲基、乙基或丙基。
3.根据权利要求1所述的N-苯基-3-苯亚甲基异吲哚-1-酮的膦酰化衍生物的制备方法，其特征在于：所述烷氧基为甲氧基、乙氧基、丙氧基或异丙氧基。
4.根据权利要求1所述的N-苯基-3-苯亚甲基异吲哚-1-酮的膦酰化衍生物的制备方法，其特征在于：所述银盐为碳酸银。
5.根据权利要求1所述的N-苯基-3-苯亚甲基异吲哚-1-酮的膦酰化衍生物的制备方法，其特征在于：所述硝酸盐为硝酸镁、硝酸钠和硝酸钾中的一种或几种。
6.根据权利要求1所述的N-苯基-3-苯亚甲基异吲哚-1-酮的膦酰化衍生物的制备方法，其特征在于：所述有机溶剂为乙腈、甲苯、四氢呋喃、N,N-二甲基甲酰胺和异丙醇中的一种或几种。
7.根据权利要求1所述的N-苯基-3-苯亚甲基异吲哚-1-酮的膦酰化衍生物的制备方法，其特征在于：所述取代N-苯基-3-苯亚甲基异吲哚-1-酮衍生物、二苯基氧膦、银盐和硝酸盐的摩尔比为1:1-3:0.05-0.2:0.5-2。
说明书 :
N-苯基-3-苯亚甲基异吲哚-1-酮的膦酰化衍生物的制备方法
技术领域
[0001] 本发明涉及有机化学领域，尤其涉及一种N-苯基-3-苯亚甲基异吲哚-1-酮的膦酰化衍生物的制备方法。
背景技术
[0002] 含氮杂环化合物是一类重要的，具有生物活性和药用价值的有机化合物。特别是异吲哚-1-酮衍生物，其是重要的医药中间体和天然产物的结构单元。目前已有关于N-苯基-3-苯亚甲基异吲哚-1-酮衍生物具有麻醉和镇静作用的相关报道。另一方面，二苯基氧膦是重要的反应有机反应中间体，并且有着很好的生理活性。N-苯基-3-苯亚甲基异吲哚-1-酮的膦酰化衍生物可能会具有更高的生理活性。因此，开发一种N-苯基-3-苯亚甲基异吲哚-1-酮衍生物的膦酰化衍生物的合成方法，合成一系列膦酰化衍生物非常重要。
[0003] 至今，芳基膦酰化的Csp2-P键的构建有两种方法。一种是依靠了芳基上的活化基团或者是定位基团的作用；另一种方法是Csp2-H键直接构建Csp2-P键。最早的芳基膦酰化的Csp2-P键的构建方法是在Pd催化剂催化下，利用芳基碘与亚磷酸酯反应合成芳基膦酸酯衍生物。此外，利用芳基三氟甲磺酸酯、二芳基碘盐、芳基硼酸进行芳基膦酰化的方法也有很多报道。但以上方法有的涉及到芳环的活化且用到昂贵的钯催化剂，有的需要合成碘盐。
[0004] 此外，有些方法是利用芳环或芳杂环上的氢直接膦酰化，但这两种方法均使用到三价锰(Mn)盐，且仅适用亚磷酸酯类化合物的膦酰化衍生物。最近也还有文献报道了利用光催化方法进行膦酰化反应。但该方法需要使用昂贵的光催化剂以及其他特殊的试剂。
[0005] 目前还未出现N-苯基-3-苯亚甲基异吲哚-1-酮的膦酰化衍生物的相关技术，以上利用活化基团或者定位基团的反应显然不符合原子经济性和环境友好性的要求，而利用Mn催化C-H键直接构建C-P键的反应，由于温度较高，时间较长，不适合N-苯基-3-苯亚甲基异吲哚-1-酮衍生物的膦酰化衍生物合成。
[0006] 总之，以上现有芳基膦酰化衍生物的合成技术中，存在操作技术要求高，反应规模不能太大等不足。因此开发反应条件温和、适用范围广泛、符合绿色化学要求的合成方法非常重要。
发明内容
[0007] 为解决上述技术问题，本发明的目的是提供一种N-苯基-3-苯亚甲基异吲哚-1-酮的膦酰化衍生物的制备方法，其具有原料来源简单、反应条件温和、普适性好的优点。
[0008] 本发明提供了一种N-苯基-3-苯亚甲基异吲哚-1-酮的膦酰化衍生物的制备方法，包括以下步骤：
[0009] 将式(1)的取代N-苯基-3-苯亚甲基异吲哚-1-酮衍生物和式(2)的二苯基氧膦在银盐的催化作用下，在含有硝酸盐的有机溶剂中于0～35℃下反应，得到式(3)的N-苯基-3-苯亚甲基异吲哚-1-酮的膦酰化衍生物，以上反应的路线图如下：
[0010]
[0011] 其中，R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11独立地选自氢、烷基、烷氧基、卤素或三氟甲基。
[0012] 进一步地，R1、R2、R3、R4、R5、R6、R7、R8、R9、R11为氢，R10为氢、烷基、烷氧基、卤素或三氟甲基；
[0013] 或R1、R2、R3、R4、R5、R6、R7、R8、R10、R11为氢，R9为氢、烷基、卤素；
[0014] 或R1、R2、R3、R4、R6、R7、R8、R9、R10、R11为氢，R5为氢、烷基、烷氧基、卤素；
[0015] 或R1、R2、R4、R5、R6、R7、R9、R10、R11为氢，R3为卤素；
[0016] 或R1、R3、R4、R5、R7、R8、R9、R10、R11为氢，R2为氢、烷基、烷氧基或卤素；
[0017] 或R2、R3、R4、R5、R6、R8、R9、R10、R11为氢，R1为氢、卤素。
[0018] 进一步地，烷基为甲基、乙基或丙基。优选地，烷基为甲基。
[0019] 进一步地，烷氧基为甲氧基、乙氧基、丙氧基或异丙氧基。优选地，烷氧基为甲氧基。
[0020] 进一步地，银盐为碳酸银。
[0021] 进一步地，硝酸盐为硝酸镁、硝酸钠和硝酸钾中的一种或几种。优选地，硝酸盐为硝酸镁。
[0022] 进一步地，有机溶剂为乙腈、甲苯、四氢呋喃、N,N-二甲基甲酰胺和异丙醇中的一种或几种。优选地，有机溶剂为乙腈。
[0023] 进一步地，取代N-苯基-3-苯亚甲基异吲哚-1-酮衍生物、二苯基氧膦、银盐和硝酸盐的摩尔比为1:1-3:0.05-0.2:0.5-2。优选地，取代N-苯基-3-苯亚甲基异吲哚-1-酮衍生物、二苯基氧膦、银盐和硝酸盐的摩尔比为1：2：0.1：2：0.2。
[0024] 优选地，反应温度为20-25℃。更优选地，反应温度为25℃。
[0025] 进一步地，反应结束后还包括对产物进行柱层析分离提纯处理的步骤。
[0026] 以上制备方法中，利用全新的催化体系即银盐和硝酸盐来引发自由基并完成反应循环，成功实现了N-苯基-3-苯亚甲基异吲哚-1-酮的膦酰化的反应。
[0027] 借由上述方案，本发明至少具有以下优点：
[0028] 1.本发明使用取代N-苯基-3-苯亚甲基异吲哚-1-酮衍生物为起始物，原料易得、种类很多；本发明将银盐和硝酸盐试剂用于N-苯基-3-苯亚甲基异吲哚-1-酮衍生物的膦酰化反应，由于选用了合适的催化剂和溶剂，尤其是选用镁盐，可以使这类磷自由基反应高效的进行芳基的膦酰化，本发明还对反应温度进行了探索，发现室温下这种自由基反应很容易进行，温度升高或下降对这类自由基反应不利。
[0029] 2.本发明反应条件温和、反应操作和后处理过程简单，产率较高，适合于规模生产。
[0030] 上述说明仅是本发明技术方案的概述，为了能够更清楚了解本发明的技术手段，并可依照说明书的内容予以实施，以下以本发明的较佳实施例并配合详细说明如后。
具体实施方式
[0031] 下面结合实施例，对本发明的具体实施方式作进一步详细描述。以下实施例用于说明本发明，但不用来限制本发明的范围。
[0032] 以下实施例中，反应式中的HPOPh2代表二苯基氧膦，其中Ph代表苯环。
[0033] 实施例1 3-苯亚甲基-2-(2-二苯氧膦)苯基异吲哚-1-酮的合成(2a)的合成
[0034]
[0035] 比较不同的有机溶剂对反应产率的影响，具体操作如(1)-(5)中的方法：
[0036] (1)称取3-苯亚甲基-2-苯基异吲哚-1-酮1a(0.297g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2a。分离产率为60％。
[0037] (2)称取3-苯亚甲基-2-苯基异吲哚-1-酮1a(0.297g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL N,N-二甲基甲酰胺(DMF)中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物
2a。分离产率为42％。
2a。分离产率为42％。
[0038] (3)称取3-苯亚甲基-2-苯基异吲哚-1-酮1a(0.297g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL四氢呋喃(THF)中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2a。分离产率为25％。
[0039] (4)称取3-苯亚甲基-2-苯基异吲哚-1-酮1a(0.297g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL异丙醇(i-PrOH)中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2a。分离产率为22％。
[0040] (5)称取3-苯亚甲基-2-苯基异吲哚-1-酮1a(0.297g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL甲苯中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2a。分离产率为23％。
[0041] 改变碳酸银的用量，比较其对产率的影响，具体操作如(6)-(7)中的方法：
[0042] (6)称取3-苯亚甲基-2-苯基异吲哚-1-酮1a(0.297g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.014g,0.05mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2a。分离产率为54％。
[0043] (7)称取3-苯亚甲基-2-苯基异吲哚-1-酮1a(0.297g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.054g,0.2mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2a。分离产率为53％。
[0044] 改变二苯基邻氧的用量，比较其对产率的影响，具体操作如(8)-(9)中的方法：
[0045] (8)称取3-苯亚甲基-2-苯基异吲哚-1-酮1a(0.297g,1mmol)，二苯基氧膦(0.202g,1mmol)，碳酸银(0.014g,0.05mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2a。分离产率为20％。
[0046] (9)称取3-苯亚甲基-2-苯基异吲哚-1-酮1a(0.297g,1mmol)，二苯基氧膦(0.606g,3mmol)，碳酸银(0.014g,0.05mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2a。分离产率为48％。
[0047] 改变反应温度，比较其对产率的影响，具体操作如(10)-(12)中的方法：
[0048] (10)称取3-苯亚甲基-2-苯基异吲哚-1-酮1a(0.297g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在35℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2a。分离产率为55％。
[0049] (11)称取3-苯亚甲基-2-苯基异吲哚-1-酮1a(0.297g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在15℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2a。分离产率为52％。
[0050] (12)称取3-苯亚甲基-2-苯基异吲哚-1-酮1a(0.297g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在0℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2a。分离产率45％。以上各方法中所得产物的核磁测试数据和HRMS(ESI-TOF)测试结果如下：
[0051] 2a:白色固体，1H NMR(400MHz,DMSO-d6)δ:8.94(d,J＝7.7Hz,1H),7.94–7.89(m,2H),7.79–7.75(m,1H),7.69(d,J＝7.7Hz,2H),7.59(d,J＝8.9Hz,3H),7.57–7.54(m,3H),
7.52–7.39(m,4H),7.37–7.32(m,2H),7.12–7.04(m,3H),6.83(t,J＝6.6Hz,2H),4.65(d,J＝10.3Hz,1H)；13C NMR(101MHz,DMSO-d6)δ:165.00(s),145.40(s),136.80(s),135.92(s),
135.80(s),134.79(s),134.70(s),133.80(s),132.02(s),131.75(s),130.65(s),130.25(s),130.17(s),129.53(s),128.60(s),128.14(s),128.02(s),127.78(s),127.67(s),
127.07(s),126.86(s),126.51(s),125.70(s),122.05(s),95.88(s),51.33(s),50.64(s)；31P NMR(162MHz,DMSO-d6)δ:27.66(s).HRMS(ESI-TOF)calcd for C33H25NO2P(M+H)+:
498.1623,found 498.1629。
7.52–7.39(m,4H),7.37–7.32(m,2H),7.12–7.04(m,3H),6.83(t,J＝6.6Hz,2H),4.65(d,J＝10.3Hz,1H)；13C NMR(101MHz,DMSO-d6)δ:165.00(s),145.40(s),136.80(s),135.92(s),
135.80(s),134.79(s),134.70(s),133.80(s),132.02(s),131.75(s),130.65(s),130.25(s),130.17(s),129.53(s),128.60(s),128.14(s),128.02(s),127.78(s),127.67(s),
127.07(s),126.86(s),126.51(s),125.70(s),122.05(s),95.88(s),51.33(s),50.64(s)；31P NMR(162MHz,DMSO-d6)δ:27.66(s).HRMS(ESI-TOF)calcd for C33H25NO2P(M+H)+:
498.1623,found 498.1629。
[0052] 实施例2 3-苯亚甲基-2-(4-甲基-2-二苯氧膦)苯基异吲哚-1-酮(2b)的合成
[0053]
[0054] 称取3-苯亚甲基-2-(4-甲基)苯基异吲哚-1-酮1b(0.311g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2b。分离产率为62％。
[0055] 2b:白色固体,62％产率；1H NMR(400MHz,DMSO-d6)δ:8.92(d,J＝7.6Hz,1H),7.95–7.83(m,2H),7.75(t,J＝7.3Hz,1H),7.54(d,J＝8.6Hz,5H),7.49–7.44(m,2H),7.41(d,J＝7.3Hz,1H),7.38–7.31(m,2H),7.18–7.09(m,3H),7.09–7.04(m,2H),6.81(d,J＝
6.1Hz,3H),4.61(d,J＝10.1Hz,1H),3.90(s,3H)；13C NMR(101MHz,DMSO-d6)δ:164.91(s),
157.56(s),145.42(s),136.91(s),135.90(s),134.89(s),134.60(s),133.90(s),131.80(s),130.87(s),130.63(s),130.24(s),130.16(s),129.43(s),128.24(s),128.11(s),
127.99(s),127.73(s),127.62(s),127.49(s),127.01(s),126.86(s),121.91(s),113.75(s),95.54(s),55.30(s),51.25(s),50.57(s)；31P NMR(162MHz,DMSO-d6)δ:27.93(s).HRMS(ESI-TOF)calcd for C34H27NO2P(M+H)+:512.1779,found 512.1780。
6.1Hz,3H),4.61(d,J＝10.1Hz,1H),3.90(s,3H)；13C NMR(101MHz,DMSO-d6)δ:164.91(s),
157.56(s),145.42(s),136.91(s),135.90(s),134.89(s),134.60(s),133.90(s),131.80(s),130.87(s),130.63(s),130.24(s),130.16(s),129.43(s),128.24(s),128.11(s),
127.99(s),127.73(s),127.62(s),127.49(s),127.01(s),126.86(s),121.91(s),113.75(s),95.54(s),55.30(s),51.25(s),50.57(s)；31P NMR(162MHz,DMSO-d6)δ:27.93(s).HRMS(ESI-TOF)calcd for C34H27NO2P(M+H)+:512.1779,found 512.1780。
[0056] 实施例3 3-苯亚甲基-2-(4-甲氧基-2-二苯氧膦)苯基异吲哚-1-酮(2c)的合成[0057]
[0058] 称取3-苯亚甲基-2-(4-甲氧基)苯基异吲哚-1-酮1c(0.327g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2c。分离产率为64％。
[0059] 2c:白色固体,64％产率；1H NMR(400MHz,DMSO-d6)δ:8.97(d,J＝7.7Hz,1H),7.94(dd,J＝9.8,4.7Hz,2H),7.78(t,J＝7.4Hz,1H),7.63–7.55(m,6H),7.50(t,J＝7.3Hz,1H),7.47–7.42(m,2H),7.41–7.35(m,3H),7.11(dd,J＝14.9,6.4Hz,3H),6.85(d,J＝6.4Hz,
2H),4.69(d,J＝10.2Hz,1H),2.49(s,3H)；13C NMR(101MHz,DMSO-d6)δ:164.96(s),145.40(s),136.83(s),135.82(s),135.65(s),134.83(s),133.84(s),133.23(s),131.89(s),
131.79(s),130.78(s),130.68(s),130.27(s),130.18(s),129.46(s),129.06(s),128.12(s),128.00(s),127.77(s),127.66(s),127.03(s),126.85(s),125.65(s),121.96(s),
51.29(s),50.60(s),20.88(s)；31P NMR(162MHz,DMSO-d6)δ:27.80(s).HRMS(ESI-TOF)calcd for C34H27NO3P(M+H)+:528.1779,found 528.1741。
2H),4.69(d,J＝10.2Hz,1H),2.49(s,3H)；13C NMR(101MHz,DMSO-d6)δ:164.96(s),145.40(s),136.83(s),135.82(s),135.65(s),134.83(s),133.84(s),133.23(s),131.89(s),
131.79(s),130.78(s),130.68(s),130.27(s),130.18(s),129.46(s),129.06(s),128.12(s),128.00(s),127.77(s),127.66(s),127.03(s),126.85(s),125.65(s),121.96(s),
51.29(s),50.60(s),20.88(s)；31P NMR(162MHz,DMSO-d6)δ:27.80(s).HRMS(ESI-TOF)calcd for C34H27NO3P(M+H)+:528.1779,found 528.1741。
[0060] 实施例4 3-苯亚甲基-2-(4-氯-2-二苯氧膦)苯基异吲哚-1-酮(2d)的合成
[0061]
[0062] 称取3-苯亚甲基-2-(4-氯)苯基异吲哚-1-酮1d(0.333g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2d。分离产率为56％。
[0063] 2d:白色固体,56％产率；1H NMR(400MHz,DMSO-d6)δ:8.97(d,J＝7.7Hz,1H),8.03–7.96(m,2H),7.77(t,J＝7.4Hz,1H),7.71(d,J＝8.8Hz,2H),7.68–7.62(m,3H),7.55(s,3H),7.51–7.38(m,5H),7.09(dd,J＝14.5,6.2Hz,3H),6.81(d,J＝6.1Hz,2H),4.72(d,J＝10.2Hz,1H)；13C NMR(101MHz,DMSO-d6)δ:164.97(s),145.34(s),136.85(s),135.84(s),
134.92(s),134.76(s),133.77(s),132.17(s),131.85(s),131.82(s),130.70(s),130.41(s),130.33(s),130.30(s),130.21(s),129.59(s),128.68(s),128.17(s),128.05(s),
127.72(s),127.61(s),127.06(s),126.95(s),122.08(s),96.09(s),51.30(s),50.62(s)；31P NMR(162MHz,DMSO-d6)δ:27.67(s).HRMS(ESI-TOF)calcd for C33H24ClNO2P(M+H)+:
532.1233,found 532.1216。
134.92(s),134.76(s),133.77(s),132.17(s),131.85(s),131.82(s),130.70(s),130.41(s),130.33(s),130.30(s),130.21(s),129.59(s),128.68(s),128.17(s),128.05(s),
127.72(s),127.61(s),127.06(s),126.95(s),122.08(s),96.09(s),51.30(s),50.62(s)；31P NMR(162MHz,DMSO-d6)δ:27.67(s).HRMS(ESI-TOF)calcd for C33H24ClNO2P(M+H)+:
532.1233,found 532.1216。
[0064] 实施例5 3-苯亚甲基-2-(4-氟-2-二苯氧膦)苯基异吲哚-1-酮(2e)的合成
[0065]
[0066] 称取3-苯亚甲基-2-(4-氟)苯基异吲哚-1-酮1e(0.315g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2e。分离产率为52％。
[0067] 2e:白色固体,52％产率；1H NMR(400MHz,DMSO-d6)δ:8.97(d,J＝7.7Hz,1H),7.99–7.94(m,2H),7.77(dd,J＝10.6,4.2Hz,1H),7.69(dd,J＝9.0,5.1Hz,2H),7.64(s,
1H),7.59–7.50(m,4H),7.49–7.45(m,3H),7.45–7.41(m,3H),7.13–7.04(m,3H),6.83(t,J
13
＝6.7Hz,2H),4.67(d,J＝10.3Hz,1H)；C NMR(101MHz,DMSO-d6)δ:165.45(s),162.56(s),
160.13(s),145.67(s),136.97(s),136.31(s),135.96(s),135.14(s),134.15(s),132.61(s),131.25(s),131.15(s),130.91(s),130.71(d,J＝8.3Hz),130.14(s),129.15(s),
128.57(d,J＝11.8Hz),128.35(s),128.24(s),127.29(s),127.04(s),126.17(s),122.61
31
(s),114.42(d,J＝21.1Hz),96.30(s),51.04(s),50.35(s)；P NMR(162MHz,DMSO-d6)δ:
27.84(s).HRMS(ESI-TOF)calcd for C33H24FNO2P(M+H)+:516.1529,found 516.1526。
1H),7.59–7.50(m,4H),7.49–7.45(m,3H),7.45–7.41(m,3H),7.13–7.04(m,3H),6.83(t,J
13
＝6.7Hz,2H),4.67(d,J＝10.3Hz,1H)；C NMR(101MHz,DMSO-d6)δ:165.45(s),162.56(s),
160.13(s),145.67(s),136.97(s),136.31(s),135.96(s),135.14(s),134.15(s),132.61(s),131.25(s),131.15(s),130.91(s),130.71(d,J＝8.3Hz),130.14(s),129.15(s),
128.57(d,J＝11.8Hz),128.35(s),128.24(s),127.29(s),127.04(s),126.17(s),122.61
31
(s),114.42(d,J＝21.1Hz),96.30(s),51.04(s),50.35(s)；P NMR(162MHz,DMSO-d6)δ:
27.84(s).HRMS(ESI-TOF)calcd for C33H24FNO2P(M+H)+:516.1529,found 516.1526。
[0068] 实施例6 3-苯亚甲基-2-(5-甲基-2-二苯氧膦)苯基异吲哚-1-酮(2f)的合成
[0069]
[0070] 称取3-苯亚甲基-2-(5-甲基)苯基异吲哚-1-酮1f(0.311g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2f。分离产率为70％。
[0071] 2f:白色固体,70％产率；1H NMR(400MHz,DMSO-d6)δ:9.00(d,J＝7.7Hz,1H),7.98–7.91(m,2H),7.77(t,J＝7.0Hz,1H),7.61(s,1H),7.55(s,4H),7.53–7.40(m,5H),
7.39–7.34(m,2H),7.27(d,J＝6.8Hz,1H),7.07(dd,J＝13.9,6.3Hz,3H),6.82(s,2H),4.68(d,J＝10.3Hz,1H),2.44(s,3H)；13C NMR(101MHz,DMSO-d6)δ:165.01(s),145.40(s),
137.84(s),136.92(s),135.97(s),134.80(s),133.81(s),132.00(s),131.78(s),130.72(s),130.29(s),130.24(s),130.15(s),129.49(s),128.35(s),128.19(s),128.07(s),
127.76(s),127.65(s),127.05(s),126.94(s),125.67(s),123.02(s),122.01(s),95.95(s),51.32(s),50.64(s),21.42(s)；31P NMR(162MHz,DMSO-d6)δ:27.73(s).HRMS(ESI-TOF)calcd for C34H27NO2P(M+H)+:512.1779,found 512.1784。
7.39–7.34(m,2H),7.27(d,J＝6.8Hz,1H),7.07(dd,J＝13.9,6.3Hz,3H),6.82(s,2H),4.68(d,J＝10.3Hz,1H),2.44(s,3H)；13C NMR(101MHz,DMSO-d6)δ:165.01(s),145.40(s),
137.84(s),136.92(s),135.97(s),134.80(s),133.81(s),132.00(s),131.78(s),130.72(s),130.29(s),130.24(s),130.15(s),129.49(s),128.35(s),128.19(s),128.07(s),
127.76(s),127.65(s),127.05(s),126.94(s),125.67(s),123.02(s),122.01(s),95.95(s),51.32(s),50.64(s),21.42(s)；31P NMR(162MHz,DMSO-d6)δ:27.73(s).HRMS(ESI-TOF)calcd for C34H27NO2P(M+H)+:512.1779,found 512.1784。
[0072] 实施例7 3-苯亚甲基-2-(5-氯-2-二苯氧膦)苯基异吲哚-1-酮(2g)的合成
[0073]
[0074] 称取3-苯亚甲基-2-(5-氯)苯基异吲哚-1-酮1g(0.331g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2g。分离产率为57％。
[0075] 2g:白色固体,70％产率；1H NMR(400MHz,DMSO-d6)δ:9.02(d,J＝7.5Hz,1H),8.03(s,2H),7.85(s,1H),7.82–7.74(m,2H),7.71(d,J＝7.7Hz,1H),7.65–7.54(m,4H),7.53–7.40(m,5H),7.16–7.02(m,3H),6.75(d,J＝58.3Hz,3H),4.78(d,J＝10.1Hz,1H)；13C NMR(101MHz,DMSO-d6)δ:165.01(s),145.30(s),137.58(s),136.92(s),135.91(s),134.72(s),133.73(s),133.10(s),132.34(s),131.84(s),130.64(s),130.33(s),130.23(s),
130.11(s),129.66(s),128.31(s),128.19(s),127.74(s),127.63(s),127.01(s),126.08(s),124.15(s),123.96(s),122.17(s),96.31(s),51.22(s),50.53(s)；31P NMR(162MHz,DMSO-d6)δ:27.56(s).HRMS(ESI-TOF)calcd for C34H27NO2P(M+H)+:532.1233,found
532.1216。
130.11(s),129.66(s),128.31(s),128.19(s),127.74(s),127.63(s),127.01(s),126.08(s),124.15(s),123.96(s),122.17(s),96.31(s),51.22(s),50.53(s)；31P NMR(162MHz,DMSO-d6)δ:27.56(s).HRMS(ESI-TOF)calcd for C34H27NO2P(M+H)+:532.1233,found
532.1216。
[0076] 实施例8 3-(4-甲基)苯亚甲基-2-(2-二苯氧膦)苯基异吲哚-1-酮(2h)的合成[0077]
[0078] 称取3-(4-甲基)苯亚甲基-2-苯基异吲哚-1-酮1h(0.331g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2h。分离产率为64％。
[0079] 2h:白色固体,64％产率；1H NMR(400MHz,DMSO-d6)δ:8.96(d,J＝7.7Hz,1H),7.95–7.87(m,2H),7.78–7.70(m,3H),7.61–7.56(m,3H),7.53(d,J＝1.8Hz,3H),7.46(dd,J＝12.8,6.6Hz,3H),7.38–7.32(m,2H),7.12–7.03(m,3H),6.56(s,2H),4.64(d,J＝10.4Hz,
1H),1.94(s,3H)；13C NMR(101MHz,DMSO-d6)δ:165.08(s),145.51(s),137.01(s),136.03(s),135.97(s),134.91(s),133.92(s),132.00(s),130.68(s),130.63(s),130.31(s),
130.21(s),130.13(s),129.48(s),128.58(s),128.11(s),127.99(s),127.81(s),127.68(d,J＝3.6Hz),127.66(s),126.87(s),126.50(s),125.71(s),95.96(s),50.84(s),50.02–
48.66(m),20.38(s)；31P NMR(162MHz,DMSO-d6)δ:27.80(s).HRMS(ESI-TOF)calcd for +
C34H27NO2P(M+H) :512.1779,found512.1763。
1H),1.94(s,3H)；13C NMR(101MHz,DMSO-d6)δ:165.08(s),145.51(s),137.01(s),136.03(s),135.97(s),134.91(s),133.92(s),132.00(s),130.68(s),130.63(s),130.31(s),
130.21(s),130.13(s),129.48(s),128.58(s),128.11(s),127.99(s),127.81(s),127.68(d,J＝3.6Hz),127.66(s),126.87(s),126.50(s),125.71(s),95.96(s),50.84(s),50.02–
48.66(m),20.38(s)；31P NMR(162MHz,DMSO-d6)δ:27.80(s).HRMS(ESI-TOF)calcd for +
C34H27NO2P(M+H) :512.1779,found512.1763。
[0080] 实施例9 3-(4-甲氧基)苯亚甲基-2-(2-二苯氧膦)苯基异吲哚-1-酮(2i)的合成[0081]
[0082] 称取3-(4-甲氧基)苯亚甲基-2-苯基异吲哚-1-酮1i(0.327g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2i。分离产率为66％。
[0083] 2i:白色固体,66％产率；1H NMR(400MHz,DMSO-d6)δ:8.95(d,J＝7.7Hz,1H),7.91(dd,J＝9.7,4.8Hz,2H),7.80–7.69(m,3H),7.58(dd,J＝18.5,11.0Hz,6H),7.47(dd,J＝15.9,6.7Hz,3H),7.39–7.31(m,2H),7.09(dd,J＝12.4,6.5Hz,3H),6.33(s,2H),4.60(d,J＝10.6Hz,1H),3.45(s,3H)；13C NMR(101MHz,DMSO-d6)δ:165.57(s),158.34(s),145.99(s),137.48(s),136.45(s),135.47(s),134.48(s),132.48(s),131.20(s),131.10(s),
130.68(s),130.61(s),129.97(s),129.07(s),128.57(s),128.46(s),128.29(s),128.18(s),127.30(s),126.98(s),126.22(s),123.90(s),122.56(s),112.88(s),96.48(s),
55.11(s),50.85(s),50.16(s)；31P NMR(162MHz,DMSO-d6)δ:28.04(s).HRMS(ESI-TOF)calcd for C34H27NO3P(M+H)+:528.1779,found 528.1734。
130.68(s),130.61(s),129.97(s),129.07(s),128.57(s),128.46(s),128.29(s),128.18(s),127.30(s),126.98(s),126.22(s),123.90(s),122.56(s),112.88(s),96.48(s),
55.11(s),50.85(s),50.16(s)；31P NMR(162MHz,DMSO-d6)δ:28.04(s).HRMS(ESI-TOF)calcd for C34H27NO3P(M+H)+:528.1779,found 528.1734。
[0084] 实施例10 3-(4-氯)苯亚甲基-2-(2-二苯氧膦)苯基异吲哚-1-酮(2j)的合成
[0085]
[0086] 称取3-(4-氯)苯亚甲基-2-苯基异吲哚-1-酮1j(0.331g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2j。分离产率为55％。
[0087] 2j:白色固体,55％产率；1H NMR(400MHz,DMSO-d6)δ:8.90(d,J＝7.7Hz,1H),7.94–7.89(m,2H),7.77(t,J＝6.8Hz,1H),7.69–7.64(m,3H),7.60–7.53(m,5H),7.50(s,
1H),7.49–7.44(m,3H),7.44–7.36(m,3H),7.15(d,J＝6.9Hz,1H),7.10(d,J＝5.3Hz,2H),
4.67(d,J＝10.2Hz,1H)；13C NMR(101MHz,DMSO-d6)δ:164.93(s),145.08(s),135.75(s),
134.69(s),134.57(s),132.16(s),131.78(s),130.60(s),130.25(s),129.71(s),128.83(s),128.68(s),128.49(s),128.16(s),128.04(s),127.93(s),127.82(s),127.40(s),
127.07(s),126.80(s),126.58(s),125.68(s),123.41(s),122.14(s),95.71(s),50.70(s),50.02(s)；31P NMR(162MHz,DMSO-d6)δ:27.52(s).HRMS(ESI-TOF)calcd for
C33H24ClNO2P(M+H)+:532.1233,found532.1234。
1H),7.49–7.44(m,3H),7.44–7.36(m,3H),7.15(d,J＝6.9Hz,1H),7.10(d,J＝5.3Hz,2H),
4.67(d,J＝10.2Hz,1H)；13C NMR(101MHz,DMSO-d6)δ:164.93(s),145.08(s),135.75(s),
134.69(s),134.57(s),132.16(s),131.78(s),130.60(s),130.25(s),129.71(s),128.83(s),128.68(s),128.49(s),128.16(s),128.04(s),127.93(s),127.82(s),127.40(s),
127.07(s),126.80(s),126.58(s),125.68(s),123.41(s),122.14(s),95.71(s),50.70(s),50.02(s)；31P NMR(162MHz,DMSO-d6)δ:27.52(s).HRMS(ESI-TOF)calcd for
C33H24ClNO2P(M+H)+:532.1233,found532.1234。
[0088] 实施例11 3-(4-氟)苯亚甲基-2-(2-二苯氧膦)苯基异吲哚-1-酮(2k)的合成
[0089]
[0090] 称取3-(4-氟)苯亚甲基-2-苯基异吲哚-1-酮1k(0.315g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2k。分离产率为54％。
[0091] 2k:白色固体,54％产率；1H NMR(400MHz,DMSO-d6)δ:8.93(d,J＝7.7Hz,1H),7.98–7.89(m,2H),7.71(dd,J＝23.9,16.3Hz,5H),7.63–7.51(m,6H),7.48(dd,J＝13.0,
6.7Hz,3H),7.38(dd,J＝9.5,8.1Hz,2H),7.16–7.05(m,3H),4.68(d,J＝10.4Hz,1H)；13C NMR(101MHz,DMSO-d6)δ:165.45(s),145.67(s),136.97(s),136.31(s),135.96(s),135.14(s),134.15(s),132.61(s),131.25(s),131.15(s),130.91(s),130.76(s),130.67(s),
130.14(s),129.15(s),128.63(s),128.51(s),128.35(s),128.24(s),127.29(s),127.04(s),126.17(s),122.61(s),114.42(d,J＝21.1Hz),96.30(s),51.04(s),50.35(s)；31P NMR(162MHz,DMSO-d6)δ:27.84(s).HRMS(ESI-TOF)calcd for C33H24FNO2P(M+H)+:516.1529,found 516.1538。
6.7Hz,3H),7.38(dd,J＝9.5,8.1Hz,2H),7.16–7.05(m,3H),4.68(d,J＝10.4Hz,1H)；13C NMR(101MHz,DMSO-d6)δ:165.45(s),145.67(s),136.97(s),136.31(s),135.96(s),135.14(s),134.15(s),132.61(s),131.25(s),131.15(s),130.91(s),130.76(s),130.67(s),
130.14(s),129.15(s),128.63(s),128.51(s),128.35(s),128.24(s),127.29(s),127.04(s),126.17(s),122.61(s),114.42(d,J＝21.1Hz),96.30(s),51.04(s),50.35(s)；31P NMR(162MHz,DMSO-d6)δ:27.84(s).HRMS(ESI-TOF)calcd for C33H24FNO2P(M+H)+:516.1529,found 516.1538。
[0092] 实施例12 3-(2-氯)苯亚甲基-2-(2-二苯氧膦)苯基异吲哚-1-酮(2l)的合成
[0093]
[0094] 称取3-(2-氯)苯亚甲基-2-苯基异吲哚-1-酮1l(0.331g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2l。分离产率为54％。
[0095] 2l:白色固体,54％产率；1H NMR(400MHz,DMSO-d6)δ:8.95(d,J＝7.8Hz,1H),8.12–7.96(m,2H),7.88–7.78(m,1H),7.71(s,1H),7.66(d,J＝1.1Hz,1H),7.63(d,J＝
7.7Hz,2H),7.58(t,J＝6.9Hz,2H),7.44(t,J＝7.8Hz,2H),7.31(t,J＝7.3Hz,1H),7.20–
7.13(m,3H),7.06–6.99(m,2H),6.95–6.89(m,1H),6.85(d,J＝7.8Hz,1H),6.78–6.70(m,
2H),5.31(d,J＝11.3Hz,1H)；13C NMR(101MHz,DMSO-d6)δ:164.86(s),145.31(s),136.19(s),135.13(s),134.77(s),133.77(s),133.39(s),132.39(s),132.26(s),131.27(s),
130.97(s),130.76(s),130.48(s),130.39(s),129.92(s),129.41(s),129.05(s),128.83(s),128.38(s),127.36(s),125.95(s),125.62(s),124.78(s),122.24(s),96.17(s),
47.61(s),46.94(s)；31P NMR(162MHz,DMSO-d6)δ:29.27(s).HRMS(ESI-TOF)calcd for C33H24ClNO2P(M+H)+:532.1233,found 532.1221。
7.7Hz,2H),7.58(t,J＝6.9Hz,2H),7.44(t,J＝7.8Hz,2H),7.31(t,J＝7.3Hz,1H),7.20–
7.13(m,3H),7.06–6.99(m,2H),6.95–6.89(m,1H),6.85(d,J＝7.8Hz,1H),6.78–6.70(m,
2H),5.31(d,J＝11.3Hz,1H)；13C NMR(101MHz,DMSO-d6)δ:164.86(s),145.31(s),136.19(s),135.13(s),134.77(s),133.77(s),133.39(s),132.39(s),132.26(s),131.27(s),
130.97(s),130.76(s),130.48(s),130.39(s),129.92(s),129.41(s),129.05(s),128.83(s),128.38(s),127.36(s),125.95(s),125.62(s),124.78(s),122.24(s),96.17(s),
47.61(s),46.94(s)；31P NMR(162MHz,DMSO-d6)δ:29.27(s).HRMS(ESI-TOF)calcd for C33H24ClNO2P(M+H)+:532.1233,found 532.1221。
[0096] 实施例13 3-苯亚甲基-2-(2-二苯氧膦)苯基-4-甲基异吲哚-1-酮(2m)的合成[0097]
[0098] 称取3-苯亚甲基-2-苯基-4-甲基异吲哚-1-酮1m(0.311g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2m。分离产率为65％。
[0099] 2m:白色固体,65％产率；1H NMR(400MHz,DMSO-d6)δ:8.76(s,1H),7.98–7.84(m,2H),7.69(d,J＝7.7Hz,2H),7.61–7.50(m,6H),7.44(t,J＝7.3Hz,1H),7.35(dd,J＝12.6,
8.2Hz,3H),7.29(d,J＝7.6Hz,1H),7.07(dd,J＝8.0,6.0Hz,3H),6.87–6.72(m,3H),4.65(d,J＝10.4Hz,1H),2.54(s,3H)；13C NMR(101MHz,DMSO-d6)δ:165.03(s),145.75(s),
142.10(s),136.84(s),136.06(s),135.84(s),134.86(s),133.87(s),131.79(s),130.68(s),130.18(s),128.55(s),128.25(s),128.12(s),128.01(s),127.78(s),127.67(s),
127.16(s),127.03(s),126.38(s),125.70(s),121.98(s),95.73(s),51.34(s),50.65(s),
21.93(s)；31P NMR(162MHz,DMSO-d6)δ:27.68(s).HRMS(ESI-TOF)calcd for C34H27NO2P(M+H)+:512.1779,found 512.1777。
8.2Hz,3H),7.29(d,J＝7.6Hz,1H),7.07(dd,J＝8.0,6.0Hz,3H),6.87–6.72(m,3H),4.65(d,J＝10.4Hz,1H),2.54(s,3H)；13C NMR(101MHz,DMSO-d6)δ:165.03(s),145.75(s),
142.10(s),136.84(s),136.06(s),135.84(s),134.86(s),133.87(s),131.79(s),130.68(s),130.18(s),128.55(s),128.25(s),128.12(s),128.01(s),127.78(s),127.67(s),
127.16(s),127.03(s),126.38(s),125.70(s),121.98(s),95.73(s),51.34(s),50.65(s),
21.93(s)；31P NMR(162MHz,DMSO-d6)δ:27.68(s).HRMS(ESI-TOF)calcd for C34H27NO2P(M+H)+:512.1779,found 512.1777。
[0100] 实施例14 3-苯亚甲基-2-(2-二苯氧膦)苯基-4-氯异吲哚-1-酮(2n)的合成
[0101]
[0102] 称取3-苯亚甲基-2-苯基-4-氯异吲哚-1-酮1n(0.331g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2n。分离产率为62％。
[0103] 2n:白色固体,62％产率；1H NMR(400MHz,DMSO-d6)δ:9.10(s,1H),7.93(dd,J＝6.3,4.5Hz,2H),7.80(s,1H),7.68(d,J＝7.8Hz,2H),7.58(dd,J＝15.6,7.3Hz,6H),7.50–
7.44(m,2H),7.44–7.36(m,2H),7.09(dd,J＝14.4,6.2Hz,3H),6.85(d,J＝5.3Hz,3H),4.69(d,J＝10.1Hz,1H)；13C NMR(101MHz,DMSO-d6)δ:164.44(s),147.74(s),137.49(s),137.12(s),136.11(s),134.94(s),133.95(s),132.05(s),131.26(s),130.91(s),130.75(d,J＝
8.3Hz),130.61(d,J＝8.5Hz),130.33(s),129.94(s),129.18(s),128.68(s),128.56(s),
128.31(s),128.20(s),127.74(s),127.50(s),127.19(s),126.02(s),124.43(s),95.97(s),51.52(s),50.84(s)；31P NMR(162MHz,DMSO-d6)δ:28.15(s).HRMS(ESI-TOF)calcd for C34H27NO2P(M+H)+:532.1233,found 532.1218。
7.44(m,2H),7.44–7.36(m,2H),7.09(dd,J＝14.4,6.2Hz,3H),6.85(d,J＝5.3Hz,3H),4.69(d,J＝10.1Hz,1H)；13C NMR(101MHz,DMSO-d6)δ:164.44(s),147.74(s),137.49(s),137.12(s),136.11(s),134.94(s),133.95(s),132.05(s),131.26(s),130.91(s),130.75(d,J＝
8.3Hz),130.61(d,J＝8.5Hz),130.33(s),129.94(s),129.18(s),128.68(s),128.56(s),
128.31(s),128.20(s),127.74(s),127.50(s),127.19(s),126.02(s),124.43(s),95.97(s),51.52(s),50.84(s)；31P NMR(162MHz,DMSO-d6)δ:28.15(s).HRMS(ESI-TOF)calcd for C34H27NO2P(M+H)+:532.1233,found 532.1218。
[0104] 实施例15 3-苯亚甲基-2-(2-二苯氧膦)苯基-5-甲基异吲哚-1-酮(2o)的合成[0105]
[0106] 称取3-苯亚甲基-2-苯基-5-甲基异吲哚-1-酮1o(0.311g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2o。分离产率为67％。
[0107] 2o:白色固体,67％产率；1H NMR(400MHz,DMSO-d6)δ:8.82(d,J＝7.8Hz,1H),7.92(dd,J＝9.8,4.6Hz,2H),7.70(d,J＝7.8Hz,2H),7.62–7.50(m,7H),7.47–7.42(m,1H),7.38–7.31(m,2H),7.27(s,1H),7.07(dd,J＝14.4,6.3Hz,3H),6.87–6.71(m,3H),4.66(d,J＝10.3Hz,1H),2.36(s,3H)；13C NMR(101MHz,DMSO-d6)δ:165.61(s),143.27(s),139.58(s),137.32(s),136.55(s),136.32(s),135.32(s),134.34(s),133.26(s),132.32(s),
132.29(s),131.37(s),131.14(s),130.71(s),129.03(s),128.60(s),128.48(s),128.23(s),128.12(s),127.52(s),127.17(s),126.88(s),126.13(s),122.69(s),96.27(s),
51.89(s),51.20(s),21.35(s)；31P NMR(162MHz,DMSO-d6)δ:27.74(s).HRMS(ESI-TOF)calcd for C34H27NO2P(M+H)+:512.1779,found 512.1766。
132.29(s),131.37(s),131.14(s),130.71(s),129.03(s),128.60(s),128.48(s),128.23(s),128.12(s),127.52(s),127.17(s),126.88(s),126.13(s),122.69(s),96.27(s),
51.89(s),51.20(s),21.35(s)；31P NMR(162MHz,DMSO-d6)δ:27.74(s).HRMS(ESI-TOF)calcd for C34H27NO2P(M+H)+:512.1779,found 512.1766。
[0108] 实施例16 3-苯亚甲基-2-(2-二苯氧膦)苯基-5-氯异吲哚-1-酮(2p)的合成
[0109]
[0110] 称取3-苯亚甲基-2-苯基-5-氯异吲哚-1-酮1p(0.331g,1mmol)，二苯基氧膦(0.404g,2mmol)，碳酸银(0.027g,0.1mmol)，六水合硝酸镁(0.512g,2mmol)溶于10mL乙腈中。混合物在25℃下搅拌反应，TLC跟踪反应直到反应完全结束。反应结束后粗产物经硅胶柱层析分离(石油醚：乙酸乙酯：二氯甲烷＝1:1:2)提纯后得到化合物2p。分离产率为55％。
[0111] 2p:白色固体,55％产率；1H NMR(400MHz,DMSO-d6)δ:9.00(d,J＝8.3Hz,1H),7.96–7.89(m,2H),7.86(dd,J＝8.3,1.8Hz,1H),7.79(s,1H),7.71(d,J＝7.9Hz,2H),7.62–
7.53(m,5H),7.47(dd,J＝8.6,4.6Hz,2H),7.42–7.35(m,2H),7.08(dd,J＝15.9,6.3Hz,
3H),6.85(d,J＝6.0Hz,3H),4.69(d,J＝10.2Hz,1H)；13C NMR(101MHz,DMSO-d6)δ:163.67(s),144.09(s),136.63(s),135.62(s),134.52(s),134.39(s),133.53(s),132.72(s),
132.09(s),131.58(s),130.76(s),130.39(s),130.27(s),130.20(s),128.91(s),128.71(s),128.17(s),128.05(s),127.82(s),127.71(s),127.27(s),126.79(s),125.61(s),
121.79(s),95.79(s),51.17(s),50.49(s)；31P NMR(162MHz,DMSO-d6)δ:28.02(s).HRMS(ESI-TOF)calcd for C33H24ClNO2P(M+H)+:532.1233,found 532.1220。
7.53(m,5H),7.47(dd,J＝8.6,4.6Hz,2H),7.42–7.35(m,2H),7.08(dd,J＝15.9,6.3Hz,
3H),6.85(d,J＝6.0Hz,3H),4.69(d,J＝10.2Hz,1H)；13C NMR(101MHz,DMSO-d6)δ:163.67(s),144.09(s),136.63(s),135.62(s),134.52(s),134.39(s),133.53(s),132.72(s),
132.09(s),131.58(s),130.76(s),130.39(s),130.27(s),130.20(s),128.91(s),128.71(s),128.17(s),128.05(s),127.82(s),127.71(s),127.27(s),126.79(s),125.61(s),
121.79(s),95.79(s),51.17(s),50.49(s)；31P NMR(162MHz,DMSO-d6)δ:28.02(s).HRMS(ESI-TOF)calcd for C33H24ClNO2P(M+H)+:532.1233,found 532.1220。
[0112] 总之，本发明公开了一种N-苯基-3-苯亚甲基异吲哚-1-酮的膦酰化衍生物的制备方法，本发明提供了一种全新的体系，利用自由基反应实现了芳基的直接膦酰化反应。
[0113] 以上所述仅是本发明的优选实施方式，并不用于限制本发明，应当指出，对于本技术领域的普通技术人员来说，在不脱离本发明技术原理的前提下，还可以做出若干改进和变型，这些改进和变型也应视为本发明的保护范围。