CN115974920A - 一种铜催化构建碳磷键的方法 - Google Patents
一种铜催化构建碳磷键的方法 Download PDFInfo
- Publication number
- CN115974920A CN115974920A CN202310081675.2A CN202310081675A CN115974920A CN 115974920 A CN115974920 A CN 115974920A CN 202310081675 A CN202310081675 A CN 202310081675A CN 115974920 A CN115974920 A CN 115974920A
- Authority
- CN
- China
- Prior art keywords
- cdcl
- nmr
- copper
- compound
- carbon
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Landscapes
- Catalysts (AREA)
Abstract
Description
技术领域
本发明涉及有机合成技术领域,具体为铜催化构建碳磷键的方法。
背景技术
含膦化合物是应用最广泛的配体、催化剂和试剂之一,在材料科学、制药和农用化学品中也有广泛的应用。
近年来,烯烃的功能化形成C-P(III)键方面取得了一些不错的进展,然而通过更简单的自由基-亲电交叉偶联反应,仍然相对未被探索。Yorimitsu和Oshima以及Studer和Smith最近的有机卤化物反应实例表明了这种方法的巨大潜力。由于二次膦在光氧化还原反应中的应用很少,而磷化氢-硼烷络合物是空气稳定的化合物,可通过柱色谱法容易分离并直接用作交叉偶联反应的膦配体前体。
铜盐由于其矿产丰富、低成本和提供强的光激发还原能力或氧化能力而成为光氧化还原催化剂的常用材料。可见光促进的铜催化策略最近被开发为C-C、C-N、C-O和C-S键形成的实用合成方法。而C(sp3)-P(III)键的构建仍然是一个挑战。
发明内容
针对现有技术中的不足之处,本发明目的在于提供一种利用廉价的铜催化剂、配体和碱实现铜催化构建碳磷键的方法,该方法具有反应简单、底物范围广、经济绿色等特点。
为实现上述目的,本发明提供如下技术方案:
一种铜催化构建含碳磷键化合物的方法,在有机溶剂中,使用式1)所示N-羟基邻苯二甲酰亚胺羧酸酯类化合物与式2)所示二取代膦化氢-硼烷络合物在铜催化剂、1,1'-联萘-2,2'-双二苯膦配体(BINAP)、碱、溶剂和可见光的作用下生成式3)所示含碳磷键化合物;
其中,R1任选自富电子或吸电子芳香取代基,含环烷烃、杂环、酯基、卤素或羰基的底物,α-氨基酰胺和金刚烷中的一种;
R2和R3任选自苯基、4-氯代苯基、4-甲基苯基、噻吩中的一种。
进一步地,所述二取代膦化氢-硼烷络合物的制备过程如下:
第一步:氮气条件下,将二取代氧膦溶于无水四氢呋喃,室温下,将苯基硅烷滴加到二取代氧膦中,搅拌48 -72h,直至固体全部转化为澄清液体;
第二步:氮气条件下,将第一步得到的澄清液体溶于无水四氢呋喃得到二取代膦氢溶液;在0℃下,将硼烷二甲硫醚的四氢呋喃溶液滴加到二取代膦氢溶液中,搅拌5h;反应结束后,除去溶剂,所得固体用二氯甲烷溶解,用快速柱层析法在硅胶上进行纯化,即得。
进一步地,所述铜催化剂六氟磷酸四乙腈铜(Cu(CH3CN)4PF6);所述碱为二异丙基乙胺。
进一步地,所述N-羟基邻苯二甲酰亚胺羧酸酯类化合物、二取代磷化氢-硼烷络合物、铜催化剂、配体和碱的摩尔比是2:1:0.1:0.1:1.5。
进一步地,所述有机溶剂为四氢呋喃、甲基叔丁基醚、1,4-二氧六环、2-甲基四氢呋喃、乙二醇二甲醚或乙酸乙酯;更优选为四氢呋喃。
进一步地,所述合成方法的具体条件是氮气下将铜催化剂、配体和溶剂放入密闭封管中室温搅拌30min,后在手套箱中加入N-羟基邻苯二甲酰亚胺羧酸酯类化合物、二取代膦化氢-硼烷络合物和碱,在室温下,在蓝光照射下反应24h,再分离提纯,即得。
进一步地,所述分离提出的方法为薄层层析或柱层析提纯法,所用展开剂为乙酸乙酯-石油醚的混合溶剂。
本发明的有益效果是:该反应使用廉价易得的羧酸为起始原料经简单合成方法合成一系列N-羟基邻苯二甲酰亚胺羧酸酯类化合物,以及简单易合成的二取代磷化氢-硼烷络合物为原料,在BINAP配体的作用下,经可见光促进铜催化实现了分子间C(sp3)-P(III)键的构建,且底物的普适性较好,反应操作简便效率高;所得的产物可以作为医药中间体或膦配体。
具体实施方式
下面将结合实施例对本发明的技术方案进行清楚、完整地描述,显然,所描述的实施例是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
此外,下面所描述的本发明不同实施方式中所涉及的技术特征只要彼此之间未构成冲突就可以相互结合。
本发明所用原料如无特殊说明均可通过市场购买。
以下实施例中所用N-羟基邻苯二甲酰亚胺羧酸酯类化合物的合成方法参照文献Org.Lett.2020,22,24,9562-9567,本案合成了以下具体结构式的N-羟基邻苯二甲酰亚胺羧酸酯类化合物。
以下实施例中所用二取代磷化氢-硼烷络合物可以通过如下合成方法制得。
第一步:氮气条件下,在10mL的Schlenk封管中将二取代氧膦(5mmol)溶于无水四氢呋喃(1mL)或者不加溶剂。在室温下,将苯基硅烷(5mmol)滴加到氧膦中,搅拌反应混合物48h-72h,直至固体全部转化为澄清液体。然后无需后处理,可直接用于下一步。
其中R2和R3任选自苯基、4-氯代苯基、4-甲基苯基、噻吩或甲基等。
第二步:氮气条件下,在100mL的Schlenk瓶中将二取代膦氢(5mmol)溶于无水四氢呋喃(10mL)。在0℃下,将硼烷二甲硫醚(5.5mmol,2.0M的四氢呋喃溶液)滴加到膦氢溶液中,搅拌反应混合物5h,得到澄清溶液。反应结束后,在真空泵上直接将溶剂及多余的硼烷二甲硫醚抽走。所得固体用DCM溶解,用快速柱层析法在硅胶上进行纯化。
以下是合成的二取代磷化氢-硼烷络合物:
实施例1:
从1a和2a出发,制得白色固体3a,80%产率。
1H NMR(400MHz,CDCl3)δ7.69-7.59(m,4H),7.53-7.37(m,6H),7.33-7.24(m,2H),7.24-7.17(m,1H),7.16-7.09(m,2H),2.71(t,J=7.4Hz,2H),2.28-2.12(m,2H),1.97-1.79(m,2H),0.89(br s,3H).
13C NMR(101MHz,CDCl3)δ140.68,132.02(d,J=9.1Hz),131.05(d,J=2.4Hz),129.34(d,J=55.0Hz),128.77,128.67,128.39(d,J=4.8Hz),126.05,36.73(d,J=14.1Hz),24.76(d,J=37.1Hz),24.40.
以实施例1为例,本发明合成路径以及合成机理解释如下:
首先,配体与CuI原位生成的络合物A,在碱的存在下与2a作用生成中间体B,B在可见光作用下生成激发态C中间体,后与氧化还原活性酯1a经单电子转移过程,生成烷基自由基及二价铜物种D,后烷基自由基与D进行氧化加成,生成中间体E,再经过还原消除得到目标化合物,完成催化循环。另一种可能途径,烷基自由基攫取2a的H质子,生成磷自由基中间体,后经过自由基-自由基偶联,最终得到目标化合物。
从1b和2a出发,制得黄色固体3b,76%产率。
1H NMR(400MHz,CDCl3)δ7.70-7.62(m,4H),7.52-7.38(m,6H),7.18-7.11(m,2H),6.97(t,J=7.5Hz,1H),6.91-6.80(m,1H),3.66(d,J=11.9Hz,2H),0.89(br s,3H).
13C NMR(101MHz,CDCl3)δ162.00(d,J=5.0Hz),159.55(d,J=5.2Hz),132.59(d,J=9.1Hz),132.23(d,J=3.8Hz),131.40(d,J=2.4Hz),128.92(d,J=3.1Hz),128.84(d,J=3.0Hz),128.67(d,J=9.9Hz),128.19,123.73(t,J=3.1Hz),119.51(d,J=4.2Hz),119.36(d,J=4.2Hz),115.26(d,J=2.5Hz),115.04(d,J=2.4Hz),26.35(d,J=2.3Hz).
从1c和2a出发,制得黄色固体3c,68%产率。
1H NMR(400MHz,CDCl3)δ7.66-7.57(m,4H),7.52-7.40(m,6H),7.29(d,J=8.0Hz,1H),7.05-6.95(m,2H),6.91(d,J=7.8Hz,1H),3.53(d,J=11.9Hz,2H),0.88(br s,3H).
13C NMR(101MHz,CDCl3)δ134.17(d,J=4.2Hz),133.12(d,J=4.6Hz),132.60(d,J=9.0Hz),131.54(d,J=2.4Hz),130.07(d,J=3.1Hz),129.53(d,J=2.7Hz),128.95(d,J=4.5Hz),128.81(d,J=9.9Hz),128.21(d,J=54.2Hz),121.91(d,J=3.2Hz),33.76(d,J=31.8Hz).
从1d和2a出发,制得白色固体3d,73%产率。
1H NMR(400MHz,CDCl3)δ7.65-7.60(m,4H),7.52-7.37(m,6H),7.05(t,J=7.9Hz,1H),6.72(dt,J=8.2,2.2Hz,1H),6.60-6.52(m,1H),6.47(q,J=2.1Hz,1H),3.60(s,3H),3.58(d,J=11.8Hz,2H),0.88(br s,3H).
13C NMR(101MHz,CDCl3)δ159.13(d,J=2.7Hz),133.29(d,J=4.5Hz),132.73,131.32(d,J=2.5Hz),129.01(d,J=2.6Hz),128.70(d,J=9.8Hz),128.68(d,J=54.0Hz),122.70(d,J=4.7Hz),115.15(d,J=4.4Hz),113.30(d,J=3.1Hz),55.04,34.18(d,J=32.1Hz).
从1e和2a出发,制得白色固体3e,73%产率。
1H NMR(400MHz,CDCl3)δ7.66-7.61(m,4H),7.50-7.37(m,6H),6.96(d,J=7.7Hz,2H),6.84(dd,J=8.1,2.2Hz,2H),3.57(d,J=11.9Hz,2H),2.26(s,3H),0.89(br s,3H).
13C NMR(101MHz,CDCl3)δ136.57(d,J=3.1Hz),132.66(d,J=8.8Hz),131.24(d,J=2.5Hz),130.12(d,J=4.6Hz),128.89(d,J=49.5Hz),128.79(d,J=2.7Hz),128.65(d,J=9.1Hz),128.59,33.63(d,J=32.5Hz),21.08(d,J=1.4Hz).
从1f和2a出发,制得黄色固体3f,68%产率。
1H NMR(400MHz,CDCl3)δ7.67-7.56(m,4H),7.52-7.38(m,6H),6.92-6.88(m,2H),6.82(t,J=8.6Hz,2H),3.56(d,J=11.8Hz,2H),0.88(br s,3H).
13C NMR(101MHz,CDCl3)δ163.17(d,J=3.4Hz),160.73(d,J=3.3Hz),132.59(d,J=8.8Hz),131.77(d,J=4.6Hz),131.69(d,J=4.6Hz),131.41(d,J=2.6Hz),128.75(d,J=9.9Hz),128.47(d,J=54.5Hz),127.50(d,J=4.1Hz),127.47(d,J=3.9Hz),115.07(d,J=2.7Hz),114.86(d,J=2.6Hz),33.25(d,J=32.6Hz).
从1g和2a出发,制得白色固体3g,75%产率。
1H NMR(400MHz,CDCl3)δ7.66-7.57(m,4H),7.51-7.36(m,6H),6.92-6.80(m,2H),6.68(d,J=8.3Hz,2H),3.72(s,3H),3.54(d,J=11.6Hz,2H),0.88(br s,3H).
13C NMR(101MHz,CDCl3)δ158.60(d,J=3.1Hz),132.66(d,J=8.8Hz),131.26(d,J=6.5Hz),131.24,128.82(d,J=53.5Hz),128.66(d,J=9.7Hz),123.58(d,J=4.5Hz),113.50(d,J=2.6Hz),55.14,33.17(d,J=32.8Hz).
从1h和2a出发,制得白色固体3h,63%产率。
1H NMR(400MHz,CDCl3)δ7.62-7.57(m,4H),7.51-7.37(m,6H),6.75(s,2H),3.68(d,J=11.7Hz,2H),2.24(s,3H),1.86(s,6H),0.90(br s,3H).
13C NMR(101MHz,CDCl3)δ137.69(d,J=4.2Hz),136.30(d,J=3.4Hz),132.83(d,J=8.8Hz),131.23(d,J=2.4Hz),129.26(d,J=53.1Hz),129.10(d,J=2.8Hz),128.59(d,J=9.6Hz),126.84(d,J=5.8Hz),28.65(d,J=30.7Hz),20.87(d,J=1.2Hz),20.70(d,J=1.3Hz).
从1i和2a出发,制得白色固体3i,61%产率。
1H NMR(400MHz,CDCl3)δ7.75-7.68(m,4H),7.52 -7.42(m,6H),7.30-7.23(m,2H),7.22-7.11(m,3H),2.93-2.71(m,2H),2.64-2.41(m,2H),0.89(s,3H).
13C NMR(101MHz,CDCl3)δ141.24(d,J=14.9Hz),132.14(d,J=9.1Hz),131.27(d,J=2.4Hz),129.48,128.90(d,J=9.8Hz),128.62,128.05,126.39,29.14(d,J=1.2Hz),27.82(d,J=35.4Hz).
从1j和2a出发,制得黄色固体3j,66%产率。
1H NMR(400MHz,CDCl3)δ7.72-7.65(m,4H),7.51-7.41(m,6H),7.33-7.27(m,2H),7.15-7.05(m,2H),2.85-2.75(m,2H),2.54-2.44(m,2H),0.88(br s,3H).
13C NMR(101MHz,CDCl3)δ143.44(d,J=14.6Hz),132.12(d,J=9.2Hz),131.38(d,J=2.5Hz),131.10,130.17,129.53,128.95(d,J=55.0Hz),128.94(d,J=9.9Hz),126.83,122.59,28.86(d,J=1.6Hz),27.63(d,J=35.5Hz).
从1k和2a出发,制得白色固体3k,54%产率。
1H NMR(400MHz,CDCl3)δ7.72-7.67(m,4H),7.49-7.42(m,6H),7.11-7.02(m,2H),6.84-6.75(m,2H),3.76(s,3H),2.82-2.69(m,2H),2.53-2.42(m,2H),0.88(s,3H).
13C NMR(101MHz,CDCl3)δ158.14,133.29(d,J=15.0Hz),132.13(d,J=9.1Hz),131.22(d,J=2.6Hz),129.55,129.00,128.86(d,J=9.7Hz),114.00,55.28,28.27(d,J=1.4Hz),28.04(d,J=35.0Hz).
从1l和2a出发,制得白色固体3l,50%产率。
1H NMR(400MHz,CDCl3)δ7.63-7.58(m,4H),7.49-7.37(m,6H),7.06-6.99(m,2H),6.87-6.76(m,2H),3.78(d,J=0.9Hz,3H),2.63(t,J=7.3Hz,2H),2.21-2.14(m,2H),1.89-1.80(m,2H),0.88(br s,3H).
13C NMR(101MHz,CDCl3)δ157.97,132.80,132.11(d,J=9.1Hz),131.11(d,J=2.4Hz),129.47(d,J=54.9Hz),129.40,128.79(d,J=9.9Hz),113.84,55.26,35.88(d,J=14.1Hz),24.74(d,J=37.3Hz),24.66.
从1m和2a出发,制得白色固体3m,65%产率。
1H NMR(400MHz,CDCl3)δ7.68-7.53(m,6H),7.48-7.41(m,2H),7.40-7.28(m,4H),7.13-7.00(m,2H),7.02-6.90(m,2H),4.02(d,J=11.3Hz,2H),3.76(s,3H),0.89(br s,3H).
13C NMR(101MHz,CDCl3)δ157.39,133.50(d,J=3.4Hz),132.79(d,J=8.8Hz),131.29(d,J=2.6Hz),129.90,129.26(d,J=5.4Hz),129.09(d,J=2.1Hz),128.76(d,J=54.5Hz),128.59(d,J=9.9Hz),127.58(d,J=3.4Hz),127.15(d,J=5.6Hz),122.56(d,J=3.1Hz),118.48,103.15(d,J=1.6Hz),55.22,31.08(d,J=31.6Hz).
从1n和2a出发,制得白色固体3n,46%产率。
1H NMR(400MHz,CDCl3)δ7.64 -7.60(m,4H),7.50-7.38(m,6H),6.84(s,1H),6.63-6.48(m,2H),4.49(t,J=8.7Hz,2H),3.53(d,J=11.6Hz,2H),3.07(t,J=8.7Hz,2H),0.89(br s,3H).
13C NMR(101MHz,CDCl3)δ159.16(d,J=3.0Hz),132.68(d,J=8.7Hz),131.23(d,J=2.4Hz),129.76(d,J=4.8Hz),128.87(d,J=53.5Hz),128.63(d,J=9.8Hz),126.96(d,J=4.3Hz),126.87(d,J=2.6Hz),123.24(d,J=4.0Hz),108.66(d,J=2.5Hz),71.23,33.46(d,J=32.8Hz),29.59.
从1o和2a出发,制得白色固体3o,73%产率。
1H NMR(400MHz,CDCl3)δ7.68-7.63(m,4H),7.49-7.40(m,6H),2.24-2.13(m,2H),1.64-1.55(m,1H),1.43-1.34(m,2H),0.88(d,J=6.6Hz,6H),0.89(br s,3H).
13C NMR(101MHz,CDCl3)δ132.12(d,J=8.8Hz),131.08(d,J=2.5Hz),129.64(d,J=54.9Hz),128.78(d,J=9.9Hz),31.52,29.25(d,J=13.7Hz),23.70,23.33,22.02.
从1p和2a出发,制得白色固体3p,58%产率。
1H NMR(400MHz,CDCl3)δ7.71-7.61(m,4H),7.51-7.40(m,6H),2.35-2.09(m,2H),1.86-1.69(m,3H),1.58-1.46(m,6H),1.10-1.02(m,2H),0.88(br s,3H).
13C NMR(101MHz,CDCl3)δ132.12(d,J=9.0Hz),131.07(d,J=2.6Hz),129.68(d,J=54.8Hz),128.78(d,J=9.9Hz),41.30(d,J=13.7Hz),32.26,28.98,25.12,24.86(d,J=37.0Hz).
从1q和2a出发,制得白色固体3q,61%产率。
1H NMR(400MHz,CDCl3)δ7.74-7.60(m,4H),7.54-7.32(m,6H),2.27-2.13(m,2H),1.74-1.57(m,4H),1.43-1.35(m,2H),1.30-1.06(m,5H),0.90
-0.80(m,J=11.7,3.0Hz,2H),0.89(br s,3H).
13C NMR(101MHz,CDCl3)δ132.11(d,J=8.8Hz),131.06(d,J=2.5Hz),129.69(d,J=54.6Hz),128.77(d,J=9.9Hz),38.81(d,J=13.3Hz),32.75,30.09,26.46,26.17,23.14(d,J=37.2Hz).
从1r和2a出发,制得白色固体3r,62%产率。
1H NMR(400MHz,CDCl3)δ7.64-7.55(m,4H),7.50-7.33(m,6H),7.14-7.08(m,1H),7.08-7.01(m,2H),6.98(dq,J=7.0,1.4Hz,2H),1.78-1.67(m,2H),1.25-1.19(m,2H),0.88(br s,3H).
13C NMR(101MHz,CDCl3)δ132.12(d,J=9.1Hz),131.06(d,J=2.4Hz),129.69(d,J=54.9Hz),128.77(d,J=9.6Hz),31.92,31.15(d,J=13.9Hz),29.65,29.63,29.60,29.56,29.40,29.35,29.02,25.61(d,J=37.0Hz),22.95,22.69,14.14.
从1s和2a出发,制得白色固体3s,69%产率。
1H NMR(400MHz,CDCl3)δ7.70-7.64(m,4H),7.51-7.38(m,6H),3.64(s,3H),2.40(t,J=6.9Hz,2H),2.33-2.20(m,2H),1.90-1.77(m,2H),0.87(br s,3H).
13C NMR(101MHz,CDCl3)δ173.08,132.12(d,J=9.1Hz),131.23(d,J=2.5Hz),129.14(d,J=55.5Hz),128.85(d,J=9.9Hz),51.63,34.57(d,J=14.4Hz),25.03(d,J=37.5Hz),18.65(d,J=1.3Hz).
从1t和2a出发,制得白色固体3t,46%产率。
1H NMR(400MHz,CDCl3)δ7.71-7.63(m,4H),7.52-7.40(m,6H),2.64(td,J=9.2,8.1,6.4Hz,2H),2.52-2.42(m,2H),2.10(s,3H),0.86(br s,3H).
13C NMR(101MHz,CDCl3)δ206.24(d,J=13.6Hz),132.08(d,J=9.2Hz),131.42(d,J=2.5Hz),128.94(d,J=10.1Hz),128.76(d,J=55.5Hz),36.84(d,J=2.3Hz),29.76,19.16(d,J=40.1Hz).
从1u和2a出发,制得黄色固体3u,67%产率。
1H NMR(400MHz,CDCl3)δ7.72-7.60(m,4H),7.50-7.40(m,6H),3.33(t,J=6.7Hz,2H),2.20(ddd,J=15.1,9.5,6.2Hz,2H),1.87-1.78(m,2H),1.52(dq,J=8.0,4.5,3.8Hz,4H),0.86(br s,3H).
13C NMR(101MHz,CDCl3)δ132.09(d,J=9.1Hz),131.21(d,J=2.4Hz),129.40(d,J=54.9Hz),128.85(d,J=9.9Hz),33.47,32.10,29.60(d,J=14.1Hz),25.54(d,J=37.1Hz),22.27.
从1v和2a出发,制得白色固体3v,67%产率。
1H NMR(400MHz,CDCl3)δ7.46(dd,J=13.2,7.5Hz,4H),7.37–7.26(m,6H),6.24(s,1H),4.40(t,J=7.1Hz,1H),3.71(s,3H),2.15–2.05(m,1H),1.83–1.69(m,1H),1.44(s,9H),0.89(br s,3H).
13C NMR(101MHz,CDCl3)δ171.40(d,J=4.8Hz),156.87,138.54(d,J=21.0Hz),132.74(d,J=16.2Hz),128.40(d,J=5.8Hz),128.25,79.69,52.46,50.92(d,J=11.4Hz),32.57(d,J=22.9Hz),28.34.
从1w和2a出发,制得白色固体3w,60%产率。
1H NMR(400MHz,CDCl3)δ7.92-7.87(m,2H),7.57-7.32(m,3H),7.35(t,J=8.7Hz,3H),7.27-7.21(m,2H),7.18-7.12(m,3H),7.11-7.02(m,2H),3.82(dq,J=14.6,7.1Hz,1H),1.58(dd,J=16.3,7.3Hz,3H),0.88(br s,3H).
13C NMR(101MHz,CDCl3)δ137.82(d,J=1.5Hz),133.08(d,J=8.2Hz),132.83(d,J=8.4Hz),132.14(d,J=9.1Hz),131.40(d,J=2.5Hz),130.90(d,J=2.4Hz),129.32(d,J=4.3Hz),128.85(d,J=9.5Hz),128.66(d,J=5.4Hz),128.16(d,J=9.9Hz),127.88(d,J=2.3Hz),127.13(d,J=2.8Hz),37.41(d,J=30.9Hz),16.35(d,J=3.4Hz).
从1x和2a出发,制得白色固体3x,50%产率。
1H NMR(400MHz,CDCl3)δ7.92-7.84(m,2H),7.56-7.45(m,3H),7.35-7.26(m,3H),7.22-7.17(m,2H),7.17-7.12(m,3H),7.11-7.04(m,2H),3.55-3.47(m,1H),2.21-1.77(m,2H),0.80(t,J=7.3Hz,3H),0.88(br s,3H).
13C NMR(101MHz,CDCl3)δ135.49(d,J=2.02Hz),133.03(d,J=8.3Hz),132.64(d,J=8.3Hz),131.35(d,J=2.5Hz),130.70(d,J=2.6Hz),129.96(d,J=4.8Hz),128.84(d,J=9.5Hz),128.77(d,J=54.5Hz),128.43,128.09(d,J=9.7Hz),127.93(d,J=2.3Hz),127.10(d,J=2.7Hz),45.38,23.44(d,J=4.4Hz),12.90(d,J=13.0Hz).
从1y和2a出发,制得白色固体3y,66%产率。
1H NMR(400MHz,CDCl3)δ7.92-7.87(m,2H),7.58-7.48(m,3H),7.37-7.25(m,3H),7.23-7.18(m,2H),7.02-6.84(m,4H),3.79(dq,J=14.7,7.2Hz,1H),2.46-2.31(m,2H),1.86-1.73(m,1H),1.58(dd,J=16.5,7.3Hz,3H),0.86(dd,J=6.5,5.2Hz,6H),0.88(br s,3H).
13C NMR(101MHz,CDCl3)δ140.59(d,J=3.0Hz),134.90(d,J=1.8Hz),133.15,132.85(d,J=8.4Hz),132.14(d,J=9.1Hz),131.34(d,J=2.3Hz),130.75(d,J=2.4Hz),129.33,128.99(d,J=4.3Hz),128.87(d,J=10.1Hz),128.81(d,J=10.1Hz),128.59(d,J=2.3Hz),128.03(d,J=9.8Hz),127.73(d,J=3.2Hz),44.94,37.16(d,J=30.9Hz),30.16(d,J=1.4Hz),22.27(d,J=9.9Hz),16.27(d,J=3.8Hz),1.04.
从1z和2a出发,制得白色固体3z,69%产率。
1H NMR(400MHz,CDCl3)δ7.90(q,J=6.3,3.6Hz,2H),7.64(dd,J=8.4,3.4Hz,3H),7.54-7.49(m,2H),7.44(q,J=8.4,7.7Hz,6H),7.34(s,3H),7.30-7.19(m,3H),3.91(ddt,J=14.4,10.8,6.9Hz,1H),1.58(ddd,J=16.2,7.3,3.8Hz,3H),0.86(s,3H).
13C NMR(101MHz,CDCl3)δ196.26,138.21,137.30,137.16(d,J=2.1Hz),133.14,133.08(d,J=2.0Hz),132.99(d,J=1.0Hz),132.77(d,J=8.2Hz),132.42,131.58,131.36,131.07(d,J=6.0Hz),129.99,128.94(d,J=10.1Hz),128.41,128.28,128.26(d,J=53.5Hz),128.08,127.43(d,J=52.1Hz),37.30(d,J=30.7Hz),16.19(d,J=3.1Hz).
从1za和2a出发,制得白色固体3za,70%产率。
1H NMR(400MHz,CDCl3)δ8.01-7.97(m,2H),7.85-7.82(m,1H),7.76-7.67(m,3H),7.61-7.51(m,3H),7.51-7.44(m,2H),7.35-7.30(m,1H),7.25-7.20(m,1H),7.18-7.06(m,3H),6.97-6.92(m,2H),4.81-4.69(m,1H),1.70(dd,J=16.4,7.1Hz,3H),0.89(br s,3H).
13C NMR(101MHz,CDCl3)δ134.47(d,J=1.5Hz),133.43(d,J=1.4Hz),133.33(d,J=8.3Hz),132.43(d,J=8.4Hz),132.20(d,J=9.1Hz),131.68(d,J=4.6Hz),131.51(d,J=2.4Hz),130.54(d,J=2.5Hz),128.91(d,J=9.5Hz),128.80,128.49(d,J=23.8Hz),128.08,127.82(d,J=9.8Hz),127.71(d,J=2.7Hz),127.16(d,J=5.3Hz),125.36(d,J=64.1Hz),125.27(d,J=2.6Hz),122.25,17.47(d,J=4.0Hz),1.03.
从1zb和2a出发,制得白色固体3zb,43%产率。
1H NMR(400MHz,CDCl3)δ7.73(tt,J=8.0,1.7Hz,4H),7.50-7.37(m,6H),2.71(tq,J=14.0,7.0Hz,1H),1.15(dd,J=16.2,6.9Hz,6H),0.87(br s,3H).
13C NMR(101MHz,CDCl3)δ132.56(d,J=8.5Hz),131.04(d,J=2.6Hz),128.74(d,J=53.4Hz),128.69(d,J=9.6Hz),23.66(d,J=36.8Hz),16.86(d,J=2.2Hz).
从1zc和2a出发,制得白色固体3zc,50%产率。
1H NMR(400MHz,CDCl3)δ7.67-7.55(m,4H),7.49-7.33(m,6H),7.32-7.19(m,3H),7.12-7.01(m,2H),2.84(ddd,J=13.3,7.9,4.8Hz,1H),2.63-2.39(m,2H),1.95-1.68(m,2H),1.18(dd,J=16.7,7.0Hz,3H),0.88(br s,3H).
13C NMR(101MHz,CDCl3)δ140.86,132.57(d,J=12.1Hz),132.48(d,J=12.1Hz),131.09(d,J=2.4Hz),130.97(d,J=2.4Hz),128.95(d,J=53.5Hz),128.73(d,J=5.0Hz),128.66,128.62,128.45,128.28(d,J=53.5Hz),126.14,33.27(d,J=12.2Hz),31.86(d,J=3.1Hz),26.80(d,J=36.5Hz),13.21(d,J=2.3Hz).
从1zd和2a出发,制得白色固体3zd,57%产率。
1H NMR(400MHz,CDCl3)δ7.74-7.68(m,4H),7.51-7.34(m,6H),2.89-2.77(m,1H),1.84-1.69(m,6H),1.66-1.57(m,2H),0.87(br s,3H).
13C NMR(101MHz,CDCl3)δ132.41(d,J=8.5Hz),130.91(d,J=2.3Hz),130.11(d,J=53.9Hz),128.63(d,J=9.6Hz),33.20(d,J=38.1Hz),28.17(d,J=3.7Hz),26.64(d,J=8.7Hz).
从1ze和2a出发,制得白色固体3ze,57%产率。
1H NMR(400MHz,CDCl3)δ7.73(t,J=8.7Hz,4H),7.47-7.40(m,6H),2.39(q,J=12.5Hz,1H),1.78-1.57(m,4H),1.54-1.40(m,2H),1.32-1.18(m,4H),0.87(br s,3H).
13C NMR(101MHz,CDCl3)δ132.63(d,J=8.4Hz),130.99(d,J=2.5Hz),128.68(d,J=9.7Hz),128.43(d,J=53.5Hz),33.67(d,J=36.2Hz),26.69(d,J=12.3Hz),26.49,25.79(d,J=1.5Hz).
从1zf和2a出发,制得白色固体3zf,60%产率。
1H NMR(400MHz,CDCl3)δ7.71(d,J=9.0Hz,2H),7.44(dt,J=25.2,7.8Hz,6H),7.33(d,J=7.7Hz,2H),7.04(s,2H),6.78(t,J=7.7Hz,1H),6.30(d,J=7.8Hz,1H),3.98(s,1H),2.61(s,1H),2.52(s,1H),2.26-2.38(m,1H),1.99-2.13(m,1H),1.68-1.79(m,1H),1.50-1.56(m,1H),0.79(br s,3H).
13C NMR(101MHz,CDCl3)δ139.30(d,J=4.2Hz),134.19(d,J=8.6Hz),132.65(d,J=8.3Hz),132.19(d,J=5.4Hz),131.42(d,J=2.6Hz),130.90(d,J=2.6Hz),129.65(d,J=54.2Hz),129.32(d,J=8.1Hz),129.31,128.74(d,J=9.6Hz),128.35(d,J=9.7Hz),127.64(d,J=51.4Hz),126.83(d,J=2.7Hz),125.00(d,J=2.3Hz),37.46(d,J=29.6Hz),28.92,24.99(d,J=3.1Hz),0.60(d,J=4.3Hz).
从1zg和2a出发,制得白色固体3zg,64%产率。
1H NMR(400MHz,CDCl3)δ7.93(d,J=35.1Hz,2H),7.71-7.47(m,5H),7.47-7.28(m,3H),5.02(d,J=53.9Hz,1H),3.76-3.35(m,2H),2.34-1.80(m,4H),1.14(d,J=63.8Hz,9H),0.86(br s,3H).
13C NMR(101MHz,CDCl3)δ133.52(d,J=8.0Hz),132.98(d,J=8.6Hz),131.58,129.43(d,J=272.4Hz),128.90(d,J=9.2Hz),47.22,29.67,28.55,28.12,24.53.
从1zh和2a出发,制得白色固体3zh,53%产率。
1H NMR(400MHz,CDCl3)δ7.77-7.70(m,4H),7.54-7.39(m,6H),4.15(d,J=22.7Hz,2H),2.82-2.41(m,3H),1.82-1.53(m,5H),1.42(s,9H),0.87(br s,3H).
13C NMR(101MHz,CDCl3)δ154.48,132.67(d,J=8.5Hz),131.36(d,J=2.5Hz),128.88(d,J=9.7Hz),127.46(d,J=53.8Hz),79.74,32.47(d,J=37.4Hz),28.38,25.84.
从1zi和2a出发,制得白色固体3zi,46%产率。
1H NMR(400MHz,CDCl3)δ7.90-7.83(m,4H),7.51-7.40(m,6H),2.00-1.91(m,9H),1.72-1.61(m,6H),0.87(br s,3H).
13C NMR(101MHz,CDCl3)δ134.29(d,J=7.7Hz),130.86(d,J=2.5Hz),128.32(d,J=9.5Hz),126.98(d,J=51.2Hz),37.15,36.28(d,J=1.5Hz),34.30(d,J=31.0Hz),28.05(d,J=9.1Hz).
从1zj和2a出发,制得白色固体3zj,62%产率。
1H NMR(400MHz,CDCl3)δ7.63-7.55(m,4H),7.50-7.33(m,6H),7.14-7.08(m,1H),7.08-7.02(m,2H),6.98(dq,J=7.0,1.4Hz,2H),1.77-1.68(m,2H),1.25-1.19(m,2H),0.88(br s,3H).
13C NMR(101MHz,CDCl3)δ139.51(d,J=1.2Hz),133.63(d,J=8.5Hz),132.00(d,J=2.3Hz),131.10(d,J=2.5Hz),128.24(d,J=9.9Hz),128.21(d,J=57.4Hz),127.70(d,J=1.5Hz),127.17(d,J=1.7Hz),20.97(d,J=49.9Hz),12.22(d,J=1.6Hz).
从2b和2b出发,制得白色固体3zk,57%产率。
1H NMR(400MHz,CDCl3)δ7.58-7.44(m,4H),7.36-7.17(m,7H),7.13(d,J=7.4Hz,2H),2.70(t,J=7.3Hz,2H),2.38(s,6H),2.21-2.14(m,2H),1.88(dt,J=12.8,7.8Hz,2H),0.91(br s,3H).
13C NMR(101MHz,CDCl3)δ141.45(d,J=2.5Hz),140.91,132.06(d,J=9.3Hz),129.56(d,J=10.1Hz),128.52,128.43,126.21(d,J=56.9Hz),126.10,36.87(d,J=14.0Hz),25.11(d,J=37.7Hz),24.54,21.47.
从2c和2c出发,制得白色固体3zl,70%产率。
1H NMR(400MHz,CDCl3)δ7.55-7.46(m,4H),7.45-7.35(m,4H),7.31-7.25(m,2H),7.24-7.17(m,1H),7.15-7.06(m,2H),2.70(t,J=7.3Hz,2H),2.24-2.09(m,2H),1.91-1.79(m,2H),0.89(s,3H).
13C NMR(101MHz,CDCl3)δ140.46,138.04(d,J=2.8Hz),133.38(d,J=9.7Hz),129.28(d,J=10.3Hz),128.53,128.49,127.58(d,J=55.0Hz),126.29,36.65(d,J=14.3Hz),24.80,24.41.
从2d和2d出发,制得白色固体3zm,60%产率。
1H NMR(400MHz,CDCl3)δ7.70-7.67(m,2H),7.61-7.58(m,2H),7.30-7.23(m,2H),7.23-7.17(m,1H),2.71(t,J=7.5Hz,2H),2.29-2.20(m,2H),1.97-1.85(m,2H),0.89(brs,3H).
13C NMR(101MHz,CDCl3)δ140.67,136.58(d,J=10.6Hz),133.47(d,J=2.8Hz),130.00(d,J=57.6Hz),128.46,128.43(d,J=11.6Hz),126.17,36.63(d,J=14.9Hz),29.35(d,J=40.4Hz),24.66.
从2e和2e出发,制得白色固体3zn,65%产率。
1H NMR(400MHz,CDCl3)δ7.70-7.64(m,2H),7.53-7.41(m,3H),7.30-7.22(m,2H),7.22-7.15(m,1H),7.10(d,J=7.4Hz,2H),2.65(t,J=6.6Hz,2H),1.90-1.68(m,4H),1.52(d,J=10.1Hz,3H),0.88(br s,3H).
13C NMR(101MHz,CDCl3)δ140.80,131.42(d,J=9.1Hz),131.26(d,J=2.5Hz),129.60(d,J=53.4Hz),128.86,128.76,128.44(d,J=1.9Hz),126.12,36.78(d,J=13.5Hz),26.74(d,J=36.4Hz),24.56,10.87(d,J=38.8Hz).
上述制得的含C(sp3)-P(III)键的化合物可以作为医药中间体或膦配体,脱除硼烷保护后还具备优异的催化性能,以化合物3v为例。
3v脱去硼烷保护即可得到化合物4(Tetrahedron:Asym.1997,8,715-738)。化合物4已被证实在不对称3+2环加成反应中表现优秀的催化能力(J.Am.Chem.Soc.2007,129,10988-10989)。
尽管本发明的实施方案已公开如上,但其并不仅仅限于说明书和实施方式中所列运用,它完全可以被适用于各种适合本发明的领域,对于熟悉本领域的人员而言,可容易地实现另外的修改,因此在不背离权利要求及等同范围所限定的一般概念下,本发明并不限于特定的细节。
Claims (7)
2.如权利要求1所述的铜催化构建含碳磷键化合物的方法,其特征在于,所述二取代膦化氢-硼烷络合物的制备过程如下:
第一步:氮气条件下,将二取代氧膦溶于无水四氢呋喃,室温下,将苯基硅烷滴加到二取代氧膦中,搅拌48-72h,直至固体全部转化为澄清液体;
第二步:氮气条件下,将第一步得到的澄清液体溶于无水四氢呋喃得到二取代膦氢溶液;在0℃下,将硼烷二甲硫醚的四氢呋喃溶液滴加到二取代膦氢溶液中,搅拌5h;反应结束后,除去溶剂,所得固体用二氯甲烷溶解,用快速柱层析法在硅胶上进行纯化,即得。
3.如权利要求1所述的铜催化构建含碳磷键化合物的方法,其特征在于,所述铜催化剂六氟磷酸四乙腈铜;所述碱为二异丙基乙胺。
4.如权利要求1所述的铜催化构建含碳磷键化合物的方法,其特征在于,所述N-羟基邻苯二甲酰亚胺羧酸酯类化合物、二取代磷化氢-硼烷络合物、铜催化剂、配体和碱的摩尔比是2:1:0.1:0.1:1.5。
5.如权利要求1所述的铜催化构建含碳磷键化合物的方法,其特征在于,所述有机溶剂为四氢呋喃、甲基叔丁基醚、1,4-二氧六环、2-甲基四氢呋喃、乙二醇二甲醚或乙酸乙酯。
6.如权利要求1所述的铜催化构建含碳磷键化合物的方法,其特征在于,所述合成方法的具体条件是氮气下将铜催化剂、配体和有机溶剂放入密闭封管中室温搅拌30min,后在手套箱中加入N-羟基邻苯二甲酰亚胺羧酸酯类化合物、二取代膦化氢-硼烷络合物和碱,室温下,在蓝光照射下反应24h,再分离提纯,即得。
7.如权利要求6所述的铜催化构建含碳磷键化合物的方法,其特征在于,所述分离提出的方法为薄层层析或柱层析提纯法,所用展开剂为乙酸乙酯-石油醚的混合溶剂。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310081675.2A CN115974920A (zh) | 2023-02-08 | 2023-02-08 | 一种铜催化构建碳磷键的方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310081675.2A CN115974920A (zh) | 2023-02-08 | 2023-02-08 | 一种铜催化构建碳磷键的方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN115974920A true CN115974920A (zh) | 2023-04-18 |
Family
ID=85959721
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202310081675.2A Pending CN115974920A (zh) | 2023-02-08 | 2023-02-08 | 一种铜催化构建碳磷键的方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN115974920A (zh) |
-
2023
- 2023-02-08 CN CN202310081675.2A patent/CN115974920A/zh active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6909009B2 (en) | Alkane and alkane group dehydrogenation with organometallic catalysts | |
KR101230940B1 (ko) | 아실포스판 및 이의 유도체의 제조방법 | |
CN110590841B (zh) | 一种氮磷配体及其制备方法和用途 | |
JP2003522162A (ja) | キラルフェロセンホスフィン及び不斉触媒反応におけるその使用 | |
JP2764338B2 (ja) | 0,0’―ジフルオロアリール配位子を含むチタノセンの製造方法 | |
US20100099875A1 (en) | New ortho-functionalized p-chiral arylphosphines and derivatives: their preparation and use in asymmetric catalysis | |
CN115974920A (zh) | 一种铜催化构建碳磷键的方法 | |
CN111187298B (zh) | 一种c2-膦酰基亚甲基吲哚化合物及其制备方法和用途 | |
JPH04159288A (ja) | 光学活性ホスフィン化合物 | |
US5124464A (en) | Method of preparing metallocene compounds | |
CN113735899B (zh) | 一种具有膦手性和轴手性化合物的合成方法 | |
CN103748065B (zh) | 2-烯基胺化合物的制造方法 | |
US4851598A (en) | Method of preparing metallocene compounds | |
JP2024512412A (ja) | 触媒カンナビノール合成および前駆体 | |
CN110026244B (zh) | 腈的α烷基化反应催化剂及其应用 | |
Komatsuzaki et al. | Synthesis of planar-chiral cobalticinium complexes | |
CN1863752A (zh) | 铜催化的芳基化 | |
JP4219622B2 (ja) | ベンザイン化合物の新規製造法 | |
CN115448949B (zh) | 一种手性烯丙基膦化合物的合成方法 | |
CN115124460B (zh) | 含配位单元的联萘轴手性配体及其制备方法和用途 | |
CN102933589A (zh) | Strecker试剂,它们的衍生物,它们的制备方法以及改进的Strecker反应 | |
US6407290B2 (en) | Process for the production of substituted 10-chloro-phenoxaphosphines or 10-bromo-phenoxaphosphines | |
CN115322222A (zh) | 一种((烷基氨基)甲基)二苯基氧化膦类化合物的光催化制备方法 | |
JP6281877B2 (ja) | 触媒前駆体および不斉鎖状化合物の合成方法 | |
CN116332712A (zh) | 一种手性硫醇和氘水促进的烯烃的不对称氘官能团化方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |