CN116284114A - 一种合成手性1,3-膦醇的方法 - Google Patents

一种合成手性1,3-膦醇的方法 Download PDF

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CN116284114A
CN116284114A CN202310273317.1A CN202310273317A CN116284114A CN 116284114 A CN116284114 A CN 116284114A CN 202310273317 A CN202310273317 A CN 202310273317A CN 116284114 A CN116284114 A CN 116284114A
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chiral
phosphine
synthesis
alcohol
phosphinols
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王超
苗旺
汤卫军
薛东
李超群
肖建良
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Shaanxi Normal University
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Abstract

本发明公开了一种合成手性1,3‑膦醇的方法，该方法以手性双膦双氮钌络合物和铜盐为催化剂，以二苯基膦和α,β‑不饱和酮类化合物为底物，在氢气氛围中通过1,4‑迈克尔加成与不对称氢化串联反应实现了一锅法合成手性1,3‑膦醇。本发明反应体系简单、操作简便、反应条件温和，反应后处理简单，手性1,3‑膦醇收率好，对映选择性和非对映选择性高(高达>99％ee，96:4dr)，底物范围广，弥补了传统的原料试剂昂贵、反应体系复杂、合成步骤冗长、对映选择性和非对映选择性不高等不足，是一种简单、高效合成手性1,3‑膦醇的方法，具有很好的应用前景。

Description

一种合成手性1,3-膦醇的方法
技术领域
本发明属于手性膦醇的合成技术领域，具体涉及一种通过一锅法合成手性1,3-膦醇的方法。
背景技术
有机膦化合物在有机合成中有着广泛的应用，并且其可以进一步进行选择性转化。对于含有羟基手性的磷化合物具有十分重要的应用，羟基可以进一步的转化为氨基、碘等官能团，并且手性可以保持。同时羟基还可以与膦氯发生取代反应生成O-P产物。这些将为手性含膦配体的发展提供新的合成方法。手性1,3-膦醇的合成也为手性化合物提供了新的合成思路和手性的补充物。
目前对于手性1,3-膦醇的合成方法较少，产物有的只有醇手性或者只有与膦原子相邻的碳手性，而对于同时具有醇手性和与膦原子相邻的碳手性的1,3-膦醇报道更少，例如：(1)2018年，Mhamdi,A.和Touil,S.课题组使用膦酮在硼氢化钠的作用下还原得到1,3-膦醇(Green.Chem.Lett.Rev.2018,11,12-17)，然而产物具有较低非对映选择性，并且无对映选择性。(2)2009年和2011年，Bakos课题组使用手性环硫酸酯与二苯基膦锂反应，然后硫酸酸解可得到手性膦醇(Inorganica.Chimica.Acta.2009,362,1650–1654；Tetrahedron:Asymmetry 2011,22,2104–2109)，然而此方法反应复杂，需要用到硫酸等危险试剂，并且底物只有一种。由于这些方法在原子经济的可持续性、非绿色溶剂的使用、底物范围有限、反应步骤冗长和低的化学收率或立体选择性等方面存在缺陷。因此发展绿色、高效而简便的方法来合成具有双手性的1,3-膦醇具有重要的意义。
发明内容
本发明的目的是提供一种反应体系简单、操作简便、合成步骤短、对映选择性和非对映选择性好的合成手性1,3-膦醇的方法。
针对上述目的，本发明所采用的技术方案是：将式I所示的二苯基膦与式II所示α,β-不饱和酮类化合物、铜盐、配体、手性双膦双氮钌络合物、无机碱、水加入有机溶剂中，在氢气氛围中20～40℃反应，反应完后硼烷的二甲硫醚溶液进行硼烷保护，分离纯化产物，得到式Ⅲ所示手性1,3-膦醇；
Figure BDA0004135341520000021
式中，R1代表芳基、取代芳基、杂环芳基中任意一种，R2代表芳基、取代芳基、杂环芳基中任意一种；其中，R1优选苯基、萘基、噻吩基、呋喃基中任意一种，或者卤素、C1～C4烷基、C1～C2烷氧基、苯基、三氟甲基中一种或两种取代的苯基；R2优选苯基、噻吩基、呋喃基、萘基中任意一种，或者卤素、C1～C4烷基、C1～C2烷氧基、苯基、三氟甲基中任意一种或两种取代的苯基。
上述配体为如下结构式所示的化合物中任意一种：
Figure BDA0004135341520000022
上述手性双膦双氮钌络合物的结构式如下所示：
Figure BDA0004135341520000023
式中，Ar代表3,5-二甲基苯基。
上述合成方法中，优选α,β-不饱和酮类化合物的用量为二苯基膦摩尔量的1～2倍。
上述合成方法中，优选配体的用量为二苯基膦摩尔量的5％～10％。
上述合成方法中，优选铜盐为氯化亚铜、碘化亚铜、溴化亚铜、四氟硼酸四乙腈铜、三氟甲磺酸四乙腈铜、六氟磷酸四乙腈铜中任意一种，其用量为二苯基膦摩尔量的1％～10％。
上述合成方法中，优选手性双膦双氮钌络合物的用量为二苯基膦摩尔量的1％～2％。
上述合成方法中，优选无机碱为氢氧化钠、氢氧化钾、磷酸钾、碳酸铯中任意一种，其用量为二苯基膦摩尔量的20％～100％。
上述合成方法中，优选有机溶剂为2-甲基四氢呋喃、四氢呋喃、甲基叔丁基醚中任意一种。
上述合成方法中，进一步优选氢气氛围中氢气压力为2～10bar。
上述合成方法中，优选水的用量为二苯基膦摩尔量的2～20倍。
上述合成方法中，优选硼烷的用量为二苯基膦摩尔量的20～40倍。
本发明的有益效果如下：
本发明反应体系简单，加入反应物、双膦双氮配位的手性钌络合物、铜盐、配体、无机碱、水、有机溶剂在氢气氛围中可一锅法得到手性1,3-膦醇，反应经济效益较高、对环境无害，反应后处理简单。此外，得到的手性1,3-膦醇具有收率好、对映选择性和非对映选择性高等特点。本发明还克服了底物范围有限、原料试剂昂贵、反应体系复杂、合成步骤冗长等缺陷，与目前追求环保、经济、绿色的化学概念相符合，具有非常重要的应用前景。
具体实施方式
下面结合实施例对本发明进一步详细说明，但本发明的保护范围并不仅限于这些实施例。
下面实施例中所用的配体、手性双膦双氮钌络合物的具体结构如下：
Figure BDA0004135341520000031
式中，Ar代表3,5-二甲基苯基。
实施例1
将1mL四氢呋喃加入到3.7mg(0.01mmol)六氟磷酸四乙腈铜与8.1mg(0.015mmol)配体中搅拌30分钟后，加入到含有50.0mg(0.24mmol)反式-查耳酮、2.4mg(0.002mmol)手性钌络合物、32.6mg(0.1mmol)碳酸铯、磁子的反应管中，然后再加入37.0mg(0.2mmol)二苯基膦、36.0μL(2mmol)水，将反应管放入高压釜中，充入10bar氢气，在30℃反应24小时。反应结束后冷却至室温，取出反应管，放入-20℃的低温反应器中，然后缓慢加入0.6mL 10mol/L硼烷的二甲硫醚溶液，加完后移到室温反应1小时，然后转移到50mL茄形瓶中，加入水淬灭，萃取，干燥，减压蒸馏，然后以石油醚与二氯甲烷体积比为1:3的混合液为洗脱剂，柱层析分离产物，得到结构式如下的白色固体：
Figure BDA0004135341520000041
上述白色固体的产率为87％，高效液相色谱测得ee值>99％，dr值为91:9。其波谱数据为：1H NMR(CDCl3,400MHz)δ(ppm):7.60-7.52(m,3H),7.43-7.37(m,5H),7.28-7.25(m,1H),7.20-7.17(m,3H),7.15-7.05(m,8H),4.38(dd,J＝10.0,4.4Hz,1H),3.29(ddd,J＝15.6,12.4,2.8Hz,1H),2.78-2.69(m,1H),2.24-2.15(m,1H),1.77(br s,1H),1.01(br q,3H)；13C NMR(CDCl3,100MHz)δ(ppm):142.7,135.2,133.3(d,JC-P＝8.5Hz),132.5(d,JC-P＝8.3Hz),131.6(d,JC-P＝2.1Hz),130.8(d,JC-P＝2.4Hz),130.1(d,JC-P＝4.5Hz),128.9(d,JC-P＝9.5Hz),128.5(d,JC-P＝53.8Hz),128.7,128.4,128.2(d,JC-P＝2.1Hz),128.1(d,JC-P＝10.0Hz),127.5(d,JC-P＝2.8Hz),127.2(d,JC-P＝51.6Hz),126.8,72.9(d,JC-P＝13.5Hz),39.7(d,JC-P＝31.3Hz),39.0(d,JC-P＝4.5Hz)；31P NMR(CDCl3,162MHz)δ(ppm):24.5(m).HRMS(ESI)m/z：C27H28BNaOP[M+Na]+理论值433.1863，实测值433.1861。
实施例2
本实施例中，用等摩尔(E)-3-苯基-1-(对甲苯基)丙-2-烯-1-酮替换实施例1中的反式-查耳酮，步骤与实施例1相同，得到结构式如下的白色固体：
Figure BDA0004135341520000042
上述白色固体的产率为84％，高效液相色谱测得ee值99％，dr值为88:12。其波谱数据为：1H NMR(CDCl3,400MHz)δ(ppm):7.62-7.52(m,3H),7.44-7.40(m,2H),7.29-7.25(m,1H),7.19-6.98(m,13H),4.34(dd,J＝10.0,4.4Hz,1H),3.29(ddd,J＝15.2,12.0,2.4Hz,1H),2.77-2.68(m,1H),2.42(s,3H),2.23-2.15(m,1H),1.70(br s,1H),1.00(br q,3H)；13CNMR(CDCl3,100MHz)δ(ppm):139.7,138.2,135.2,133.4(d,JC-P＝8.2Hz),132.5(d,JC-P＝8.3Hz),131.6(d,JC-P＝2.2Hz),130.8(d,JC-P＝2.2Hz),130.1(d,JC-P＝4.4Hz),129.4,128.9(d,JC-P＝9.5Hz),128.6(d,JC-P＝54.0Hz),128.2(d,JC-P＝2.3Hz),128.1(d,JC-P＝9.6Hz),127.5(d,JC-P＝2.6Hz),127.2(d,JC-P＝50.7Hz),126.8,72.8(d,JC-P＝13.7Hz),39.8(d,JC-P＝31.3Hz),38.8(d,JC-P＝4.2Hz),21.4；31P NMR(CDCl3,162MHz)δ(ppm):24.4(m).HRMS(ESI)m/z：C28H30BNaOP[M+Na]+理论值447.2020，实测值447.2022。
实施例3
本实施例中，用等摩尔(E)-1-(4-氟苯基)-3-苯基丙-2-烯-1-酮替换实施例1中的反式-查耳酮，步骤与实施例1相同，得到结构式如下的白色固体：
Figure BDA0004135341520000051
上述白色固体的产率为85％，高效液相色谱测得ee值>99％，dr值为91:9。其波谱数据为：1H NMR(CDCl3,400MHz)δ(ppm):7.64-7.59(m,2H),7.57-7.53(m,1H),7.46-7.42(m,2H),7.30-7.26(m,1H),7.19-7.02(m,13H),4.38(dd,J＝10.0,4.8Hz,1H),3.26(ddd,J＝15.2,12.0,2.8Hz,1H),2.77-2.68(m,1H),2.20-2.11(m,1H),1.69(br s,1H),1.00(br q,3H)；13C NMR(CDCl3,100MHz)δ(ppm):162.7(d,JC-F＝245.1Hz),138.5(d,JC-F＝3.0Hz),135.1,133.3(d,JC-P＝8.2Hz),132.6(d,JC-P＝8.2Hz),131.7(d,JC-P＝2.1Hz),130.9(d,JC-P＝2.2Hz),130.0(d,JC-P＝4.4Hz),128.9(d,JC-P＝9.5Hz),128.5(d,JC-F＝8.0Hz),128.32(d,JC-P＝2.2Hz),128.3(d,JC-P＝54.0Hz),128.2(d,JC-P＝9.9Hz),127.6(d,JC-P＝2.7Hz),127.2(d,JC-P＝51.6Hz),115.6(d,JC-F＝21.3Hz),72.2(d,JC-P＝13.5Hz),39.9(d,JC-P＝31.3Hz),39.1(d,JC-P＝4.7Hz)；31P NMR(CDCl3,162MHz)δ(ppm):24.4(m).HRMS(ESI)m/z：C27H27BFNaOP[M+Na]+理论值451.1769，实测值451.1773。
实施例4
本实施例中，用等摩尔(E)-1-(4-氯苯基)-3-苯基丙-2-烯-1-酮替换实施例1中的反式-查耳酮，步骤与实施例1相同，得到结构式如下的白色固体：
Figure BDA0004135341520000061
上述白色固体的产率为88％，高效液相色谱测得ee值>99％，dr值为95:5。其波谱数据为：1H NMR(CDCl3,400MHz)δ(ppm):7.64-7.59(m,2H),7.57-7.53(m,1H),7.46-7.42(m,2H),7.34-7.28(m,3H),7.19-7.01(m,11H),4.38(dd,J＝9.6,4.8Hz,1H),3.27(ddd,J＝15.2,12.0,2.8Hz,1H),2.77-2.68(m,1H),2.19-2.11(m,1H),1.76(br s,1H),1.01(br q,3H)；13C NMR(CDCl3,100MHz)δ(ppm):141.2,135.0,134.0,133.2(d,JC-P＝8.2Hz),132.5(d,JC-P＝8.2Hz),131.7(d,JC-P＝2.1Hz),130.9(d,JC-P＝2.2Hz),130.0(d,JC-P＝4.5Hz),128.9(d,JC-P＝9.5Hz),128.8,128.3(d,JC-P＝2.1Hz),128.2(d,JC-P＝53.9Hz),128.16(d,JC-P＝9.7Hz),128.1,127.6(d,JC-P＝2.7Hz),127.1(d,JC-P＝51.6Hz),72.2(d,JC-P＝13.5Hz),39.8(d,JC-P＝31.1Hz),39.0(d,JC-P＝4.8Hz)；31PNMR(CDCl3,162MHz)δ(ppm):24.5(m).HRMS(ESI)m/z：C27H27BClNaOP[M+Na]+理论值467.1473，实测值467.1475。
实施例5
本实施例中，用等摩尔(E)-3-苯基-1-(4-(三氟甲基)苯基)丙-2-烯-1-酮替换实施例1中的反式-查耳酮，步骤与实施例1相同，得到结构式如下的白色固体：
Figure BDA0004135341520000062
上述白色固体的产率为92％，高效液相色谱测得ee值>99％，dr值为93:7。其波谱数据为：1H NMR(CDCl3,400MHz)δ(ppm):7.63-7.59(m,4H),7.57-7.53(m,1H),7.44-7.40(m,2H),7.30-7.26(m,1H),7.24-7.04(m,11H),4.50(dd,J＝9.2,5.2Hz,1H),3.33(ddd,J＝15.2,11.6,2.8Hz,1H),2.79-2.69(m,1H),2.26-2.17(m,1H),1.75(br s,1H),1.00(br q,3H)；13C NMR(CDCl3,100MHz)δ(ppm):146.9,135.2(d,JC-P＝1.1Hz),133.2(d,JC-P＝8.4Hz),132.6(d,JC-P＝8.3Hz),131.8(d,JC-P＝2.1Hz),130.9(d,JC-P＝2.4Hz),130.5(q,JC-F＝32.4Hz),130.0(d,JC-P＝4.4Hz),129.0(d,JC-P＝9.5Hz),128.4(d,JC-P＝1.9Hz),128.2(d,JC-P＝9.7Hz),128.1(d,JC-P＝53.9Hz),127.7(d,JC-P＝2.6Hz),127.2(d,JC-P＝51.7Hz),127.0,125.6(q,JC-F＝3.6Hz),124.2(q,JC-F＝270.0Hz),72.3(d,JC-P＝13.1Hz),39.7(d,JC-P＝31.0Hz),39.4(d,JC-P＝5.1Hz)；31P NMR(CDCl3,162MHz)δ(ppm):24.5(m).HRMS(ESI)m/z：C28H27BF3NaOP[M+Na]+理论值501.1737，实测值501.1736。
实施例6
本实施例中，用等摩尔(E)-1-(3-氟苯基)-3-苯基丙-2-烯-1-酮替换实施例1中的反式-查耳酮，步骤与实施例1相同，得到结构式如下的白色固体：
Figure BDA0004135341520000071
上述白色固体的产率为87％，高效液相色谱测得ee值>99％，dr值为93:7。其波谱数据为：1H NMR(CDCl3,400MHz)δ(ppm):7.61-7.53(m,3H),7.45-7.38(m,5H),7.31-7.27(m,1H),7.18-7.09(m,7H),6.89(t,J＝8.4Hz,1H),6.83(d,J＝8.0Hz,1H),6.76(d,J＝10.0Hz,1H),4.38(dd,J＝9.6,4.4Hz,1H),3.31(ddd,J＝15.2,11.6,2.4Hz,1H),2.73-2.64(m,1H),2.25-2.16(m,1H),1.72(br s,1H),0.99(br q,3H)；13C NMR(CDCl3,100MHz)δ(ppm):162.6(dd,J＝244.8,2.7Hz),142.6,138.0(d,J＝7.2Hz),133.3(d,JC-P＝8.5Hz),132.5(d,JC-P＝8.6Hz),131.8(d,JC-P＝2.2Hz),131.0(d,JC-P＝2.2Hz),129.6(dd,J＝8.4,2.3Hz),129.0(d,JC-P＝9.7Hz),128.8,128.6,128.3(d,JC-P＝9.8Hz),128.2(d,JC-P＝53.9Hz),126.8(d,JC-P＝51.8Hz),126.7,125.8(dd,J＝4.2,3.0Hz),116.9(dd,J＝22.0,4.3Hz),114.5(dd,J＝21.0,2.8Hz),72.8(d,JC-P＝13.1Hz),39.5(d,JC-P＝31.1Hz),39.0(d,JC-P＝4.3Hz)；31PNMR(CDCl3,162MHz)δ(ppm):24.9(m).HRMS(ESI)m/z：C27H27BFNaOP[M+Na]+理论值451.1769，实测值451.1764。
实施例7
本实施例中，用等摩尔(E)-1-(3-氯苯基)-3-苯基丙-2-烯-1-酮替换实施例1中的反式-查耳酮，步骤与实施例1相同，得到结构式如下的白色固体：
Figure BDA0004135341520000072
上述白色固体的产率为91％，高效液相色谱测得ee值>99％，dr值为94:6。其波谱数据为：1H NMR(CDCl3,400MHz)δ(ppm):7.66-7.61(m,2H),7.59-7.55(m,1H),7.49-7.46(m,2H),7.36-7.33(m,1H),7.30-7.26(m,2H),7.20-7.03(m,10H),6.95(d,J＝7.6Hz,1H),4.38(dd,J＝9.6,4.4Hz,1H),3.28(ddd,J＝15.2,11.6,2.8Hz,1H),2.77-2.68(m,1H),2.20-2.12(m,1H),1.71(br s,1H),1.00(br q,3H)；13C NMR(CDCl3,100MHz)δ(ppm):144.8,135.0,134.8,133.3(d,JC-P＝8.2Hz),132.5(d,JC-P＝8.5Hz),131.8,130.9,130.0(d,JC-P＝4.4Hz),129.9,129.0(d,JC-P＝9.5Hz),128.6,128.33,128.3
(d,JC-P＝51.2Hz),128.2(d,JC-P＝9.7Hz),127.6,127.0(d,JC-P＝48.5Hz),126.8,125.2,72.4(d,JC-P＝13.3Hz),39.8(d,JC-P＝31.3Hz),39.0(d,JC-P＝4.5Hz)；31P NMR(CDCl3,162MHz)δ(ppm):24.7(m).HRMS(ESI)m/z：C27H27BClNaOP[M+Na]+理论值467.1473，实测值467.1466。
实施例8
本实施例中，用等摩尔(E)-3-苯基-1-(3-(三氟甲基)苯基)丙-2-烯-1-酮替换实施例1中的反式-查耳酮，步骤与实施例1相同，得到结构式如下的白色固体：
Figure BDA0004135341520000081
上述白色固体的产率为90％，高效液相色谱测得ee值>99％，dr值为96:4。其波谱数据为：1H NMR(CDCl3,400MHz)δ(ppm):7.65-7.61(m,3H),7.57-7.53(m,1H),7.48-7.41(m,4H),7.30-7.26(m,1H),7.26-7.22(m,1H),7.19-7.06(m,7H),7.02-7.00(m,2H),4.49(dd,J＝9.2,4.8Hz,1H),3.28(ddd,J＝15.6,12.0,3.2Hz,1H),2.82-2.73(m,1H),2.24-2.15(m,1H),1.78(br s,1H),0.99(br q,3H)；13C NMR(CDCl3,100MHz)δ(ppm):143.8,134.9,133.2(d,JC-P＝8.3Hz),132.5(d,JC-P＝8.5Hz),131.8(d,JC-P＝2.3Hz),131.1(q,JC-F＝32.2Hz),130.9(d,JC-P＝2.4Hz),130.2,130.0(d,JC-P＝4.4Hz),129.1,129.0,128.4(d,JC-P＝2.2Hz),128.3,128.2(d,JC-P＝54.1Hz),128.17,127.7(d,JC-P＝2.8Hz),127.1(d,JC-P＝51.5Hz),125.1(q,JC-F＝3.7Hz),124.1(q,JC-F＝270.9Hz),123.4(q,JC-F＝3.6Hz),72.4(d,JC-P＝13.2Hz),39.8(d,JC-P＝31.2Hz),39.0(d,JC-P＝4.8Hz)；31P NMR(CDCl3,162MHz)δ(ppm):24.3(m).HRMS(ESI)m/z：C28H27BF3NaOP[M+Na]+理论值501.1737，实测值501.1735。
实施例9
本实施例中，用等摩尔(E)-3-苯基-1-(噻吩-2-基)丙-2-烯-1-酮替换实施例1中的反式-查耳酮，步骤与实施例1相同，得到结构式如下的白色固体：
Figure BDA0004135341520000091
上述白色固体的产率为88％，高效液相色谱测得ee值98％，dr值为90:10。其波谱数据为：1H NMR(CDCl3,400MHz)δ(ppm):7.73-7.68(m,2H),7.57-7.53(m,1H),7.48-7.44(m,2H),7.37-7.33(m,1H),7.31-7.27(m,1H),7.19-7.15(m,7H),7.07-7.06(m,2H),7.01-6.98(m,1H),6.75-6.745(m,1H),4.65(dd,J＝10.0,4.0Hz,1H),3.43(ddd,J＝15.6,12.4,2.8Hz,1H),2.84-2.75(m,1H),2.26-2.17(m,1H),1.87(br s,1H),1.01(br q,3H)；13C NMR(CDCl3,100MHz)δ(ppm):146.6,135.0,133.4(d,JC-P＝8.5Hz),132.6(d,JC-P＝8.5Hz),131.7(d,JC-P＝2.4Hz),130.9(d,JC-P＝2.3Hz),130.1(d,JC-P＝4.5Hz),129.0(d,JC-P＝9.6Hz),128.4(d,JC-P＝53.9Hz),128.3(d,JC-P＝2.5Hz),128.2(d,JC-P＝9.8Hz),127.6(d,JC-P＝2.6Hz),127.1(d,JC-P＝51.7Hz),126.8,125.5,125.2,68.8(d,JC-P＝14.1Hz),40.0(d,JC-P＝31.5Hz),39.5(d,JC-P＝4.6Hz)；31P NMR(CDCl3,162MHz)δ(ppm):24.4(m).HRMS(ESI)m/z：C25H26BNaOPS[M+Na]+理论值439.1427，实测值439.1431。
实施例10
本实施例中，用等摩尔(E)-1-(呋喃-2-基)-3-苯基丙-2-烯-1-酮替换实施例1中的反式-查耳酮，步骤与实施例1相同，得到结构式如下的白色固体：
Figure BDA0004135341520000092
上述白色固体的产率为74％，高效液相色谱测得ee值99％，dr值为93:7。其波谱数据为：1H NMR(CDCl3,400MHz)δ(ppm):7.77-7.73(m,2H),7.59-7.55(m,1H),7.51-7.47(m,2H),7.43-7.42(m,1H),7.31-7.28(m,1H),7.21-7.16(m,7H),7.06-7.05(m,2H),6.38(dd,J＝3.2,2.0Hz,1H),6.09(d,J＝3.2Hz,1H),4.40(dd,J＝10.4,4.4Hz,1H),3.38(ddd,J＝15.2,12.0,2.4Hz,1H),2.74-2.65(m,1H),2.46-2.37(m,1H),1.74(br s,1H),1.00(br q,3H)；13C NMR(CDCl3,100MHz)δ(ppm):154.6,142.5,135.1,133.3(d,JC-P＝8.5Hz),132.6(d,JC-P＝8.5Hz),131.7(d,JC-P＝2.2Hz),130.9(d,JC-P＝2.2Hz),129.9(d,JC-P＝4.5Hz),129.0(d,JC-P＝9.5Hz),128.5(d,JC-P＝45.8Hz),128.3,128.2,127.6(d,JC-P＝2.5Hz),127.4(d,JC-P＝51.5Hz),110.5,107.9,66.3(d,JC-P＝14.1Hz),39.9(d,JC-P＝31.6Hz),36.4(d,JC-P＝4.7Hz)；31P NMR(CDCl3,162MHz)δ(ppm):24.3(m).HRMS(ESI)m/z：C25H26BNaO2P[M+Na]+理论值423.1656，实测值423.1661。
实施例11
本实施例中，用等摩尔(E)-3-(4-甲氧基苯基)-1-苯基丙-2-烯-1-酮替换实施例1中的反式-查耳酮，步骤与实施例1相同，得到结构式如下的白色固体：
Figure BDA0004135341520000101
上述白色固体的产率为90％，高效液相色谱测得ee值>99％，dr值为90:10。其波谱数据为：1H NMR(CDCl3,400MHz)δ(ppm):7.59-7.51(m,3H),7.43-7.35(m,5H),7.30-7.26(m,1H),7.17-7.07(m,6H),6.96(dd,J＝8.4,1.6Hz,2H),6.73(d,J＝8.4Hz,2H),4.39(dd,J＝9.6,4.4Hz,1H),3.78(s,3H),3.23(ddd,J＝15.6,12.4,2.8Hz,1H),2.73-2.63(m,1H),2.20-2.12(m,1H),1.68(br s,1H),0.97(br q,3H)；13C NMR(CDCl3,100MHz)δ(ppm):159.0(d,JC-P＝2.7Hz),142.8,133.3(d,JC-P＝8.2Hz),132.6(d,JC-P＝8.2Hz),131.6(d,JC-P＝2.2Hz),131.1(d,JC-P＝4.5Hz),130.8(d,JC-P＝2.2Hz),128.9(d,JC-P＝9.5Hz),128.73,128.7(d,JC-P＝51.6Hz),128.5,128.2(d,JC-P＝9.9Hz),127.3(d,JC-P＝51.1Hz),126.8,113.7(d,JC-P＝2.1Hz),73.0(d,JC-P＝13.7Hz),55.3,39.1,38.9(d,JC-P＝35.4Hz)；31P NMR(CDCl3,162MHz)δ(ppm):24.0(m).HRMS(ESI)m/z：C28H30BNaO2P[M+Na]+理论值463.1969，实测值463.1969。
实施例12
本实施例中，用等摩尔(E)-3-([1,1'-二苯基]-4-基)-1-苯基丙-2-烯-1-酮替换实施例1中的反式-查耳酮，步骤与实施例1相同，得到结构式如下的白色固体：
Figure BDA0004135341520000102
上述白色固体的产率为89％，高效液相色谱测得ee值>99％，dr值为91:9。其波谱数据为：1H NMR(CDCl3,400MHz)δ(ppm):7.64-7.53(m,5H),7.47-7.34(m,10H),7.29-7.26(m,1H),7.15-7.13(m,8H),4.44(dd,J＝10.0,4.4Hz,1H),3.36(ddd,J＝15.2,12.0,2.4Hz,1H),2.83-2.74(m,1H),2.28-2.19(m,1H),1.83(br s,1H),1.03(br q,3H)；13C NMR(CDCl3,100MHz)δ(ppm):142.7,140.6,140.2(d,JC-P＝2.9Hz),134.3,133.3(d,JC-P＝8.4Hz),132.6(d,JC-P＝8.3Hz),131.6(d,JC-P＝2.1Hz),130.8(d,JC-P＝2.2Hz),130.5(d,JC-P＝4.4Hz),129.0,128.9,128.8,128.5(d,JC-P＝55.2Hz),128.47,128.2(d,JC-P＝9.7Hz),127.5,127.2(d,JC-P＝51.4Hz),127.0,126.8,72.9(d,JC-P＝13.5Hz),39.5(d,JC-P＝31.2Hz),39.0(d,JC-P＝4.5Hz)；31P NMR(CDCl3,162MHz)δ(ppm):24.5(m).HRMS(ESI)m/z：C33H32BNaOP[M+Na]+理论值509.2176，实测值509.2182。
实施例13
本实施例中，用等摩尔(E)-3-(4-氯苯基)-1-苯基丙-2-烯-1-酮替换实施例1中的反式-查耳酮，步骤与实施例1相同，得到结构式如下的白色固体：
Figure BDA0004135341520000111
上述白色固体的产率为86％，高效液相色谱测得ee值>99％，dr值为94:6。其波谱数据为：1H NMR(CDCl3,400MHz)δ(ppm):7.60-7.53(m,3H),7.45-7.35(m,5H),7.32-7.28(m,1H),7.19-7.06(m,8H),6.96(dd,J＝8.4,1.6Hz,2H),4.34(dd,J＝10.0,4.8Hz,1H),3.28(ddd,J＝15.6,12.0,2.8Hz,1H),2.72-2.63(m,1H),2.23-2.14(m,1H),1.82(br s,1H),0.98(br q,3H)；13C NMR(CDCl3,100MHz)δ(ppm):142.5,133.9,133.4(d,JC-P＝3.5Hz),133.3(d,JC-P＝8.5Hz),132.5(d,JC-P＝8.5Hz),131.8(d,JC-P＝2.2Hz),131.3(d,JC-P＝4.5Hz),131.0(d,JC-P＝2.3Hz),129.0(d,JC-P＝9.6Hz),128.8,128.6,128.4,128.3(d,JC-P＝12.5Hz),128.2(d,JC-P＝53.9Hz),126.8(d,JC-P＝51.8Hz),126.7,72.8(d,JC-P＝13.1Hz),39.2(d,JC-P＝31.3Hz),38.8(d,JC-P＝4.2Hz)；31P NMR(CDCl3,162MHz)δ(ppm):24.4(m).HRMS(ESI)m/z：C27H27BClNaOP[M+Na]+理论值467.1473，实测值467.1475。
实施例14
本实施例中，用等摩尔(E)-3-(3-甲氧基苯基)-1-苯基丙-2-烯-1-酮替换实施例1中的反式-查耳酮，步骤与实施例1相同，得到结构式如下的白色固体：
Figure BDA0004135341520000121
上述白色固体的产率为88％，高效液相色谱测得ee值>99％，dr值为89:11。其波谱数据为：1H NMR(CDCl3,400MHz)δ(ppm):7.60-7.51(m,3H),7.43-7.37(m,5H),7.29-7.26(m,1H),7.16-7.06(m,7H),6.74(d,J＝8.4Hz,1H),6.65(s,1H),6.60(d,J＝7.6Hz,1H),4.41(dd,J＝10.0,4.8Hz,1H),3.70(s,3H),3.27(ddd,J＝15.2,12.0,2.8Hz,1H),2.76-2.67(m,1H),2.24-2.15(m,1H),1.75(br s,1H),1.05(br q,3H)；13C NMR(CDCl3,100MHz)δ(ppm):159.5(d,JC-P＝2.3Hz),142.8,136.8,133.3(d,JC-P＝8.2Hz),132.6(d,JC-P＝8.2Hz),131.6(d,JC-P＝2.2Hz),130.8(d,JC-P＝2.2Hz),129.2(d,JC-P＝2.1Hz),128.9(d,JC-P＝9.5Hz),128.7,128.6(d,JC-P＝54.1Hz),128.5,128.2(d,JC-P＝9.9Hz),127.3(d,JC-P＝51.7Hz),126.9,122.6(d,JC-P＝4.8Hz),114.9(d,JC-P＝4.3Hz),113.9(d,JC-P＝2.8Hz),73.0(d,JC-P＝13.7Hz),55.3,39.8(d,JC-P＝31.3Hz),39.1(d,JC-P＝4.5Hz)；31P NMR(CDCl3,162MHz)δ(ppm):24.5(m).HRMS(ESI)m/z：C28H30BNaO2P[M+Na]+理论值463.1969，实测值463.1963。
实施例15
本实施例中，用等摩尔(E)-3-(3-溴苯基)-1-苯基丙-2-烯-1-酮替换实施例1中的反式-查耳酮，步骤与实施例1相同，得到结构式如下的白色固体：
Figure BDA0004135341520000122
上述白色固体的产率为83％，高效液相色谱测得ee值>99％，dr值为94:6。其波谱数据为：1H NMR(CDCl3,400MHz)δ(ppm):7.61-7.53(m,3H),7.45-7.41(m,2H),7.40-7.37(m,3H),7.33-7.29(m,2H),7.19-7.15(m,2H),7.12-7.01(m,7H),4.38(dd,J＝10.0,4.8Hz,1H),3.27(ddd,J＝15.2,12.0,2.8Hz,1H),2.72-2.62(m,1H),2.25-2.16(m,1H),1.77(brs,1H),0.97(br q,3H)；13C NMR(CDCl3,100MHz)δ(ppm):142.6,137.8,133.3(d,JC-P＝8.5Hz),133.0(d,JC-P＝4.4Hz),132.5(d,JC-P＝8.4Hz),131.8(d,JC-P＝2.3Hz),131.1(d,JC-P＝2.2Hz),130.6(d,JC-P＝2.8Hz),129.7(d,JC-P＝2.2Hz),129.0(d,JC-P＝9.6Hz),128.8,128.6,128.56,128.3(d,JC-P＝10.0Hz),128.1(d,JC-P＝54.1Hz),126.72(d,JC-P＝51.9Hz),126.7,122.2(d,JC-P＝2.9Hz),72.8(d,JC-P＝13.0Hz),39.5(d,JC-P＝30.9Hz),38.8(d,JC-P＝4.1Hz)；31P NMR(CDCl3,162MHz)δ(ppm):24.9(m).HRMS(ESI)m/z：C27H27BBrNaOP[M+Na]+理论值511.0968，实测值511.0967。
上述实施例中，所用的铜盐也可以用氯化亚铜、碘化亚铜、溴化亚铜、四氟硼酸四乙腈铜、三氟甲磺酸四乙腈铜中任意一种替换；配体可用下述结构式所示的化合物中任意一种替换，无机碱可用氢氧化钠、氢氧化钾、磷酸钾中任意一种替换，有机溶剂可用2-甲基四氢呋喃、甲基叔丁基醚中任意一种替换，其均可实现本发明的目的，达到收率好、对映选择性和非对映选择性高的手性1,3-膦醇。
Figure BDA0004135341520000131
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Claims (10)

1.一种合成手性1,3-膦醇的方法，其特征在于：将式I所示的二苯基膦与式II所示α,β-不饱和酮类化合物、铜盐、配体、手性双膦双氮钌络合物、无机碱、水加入有机溶剂中，在氢气氛围中20～40℃下反应，反应完后加入硼烷的二甲硫醚溶液进行硼烷保护，分离纯化产物，得到式Ⅲ所示手性1,3-膦醇；
Figure FDA0004135341510000011
式中，R1、R2各自独立的代表芳基、取代芳基、杂环芳基中任意一种；
所述铜盐为氯化亚铜、碘化亚铜、溴化亚铜、四氟硼酸四乙腈铜、三氟甲磺酸四乙腈铜、六氟磷酸四乙腈铜中任意一种；
所述配体为下述结构式所示的化合物中任意一种：
Figure FDA0004135341510000012
所述手性双膦双氮钌络合物的结构式如下所示：
Figure FDA0004135341510000013
式中，Ar代表3,5-二甲基苯基。
2.根据权利要求1所述的合成手性1,3-膦醇的方法，其特征在于：所述R1代表苯基、萘基、噻吩基、呋喃基中任意一种，或者卤素、C1～C4烷基、C1～C2烷氧基、苯基、三氟甲基中一种或两种取代的苯基。
3.根据权利要求1所述的合成手性1,3-膦醇的方法，其特征在于：所述R2代表苯基、噻吩基、呋喃基、萘基中任意一种，或者卤素、C1～C4烷基、C1～C2烷氧基、苯基、三氟甲基中任意一种或两种取代的苯基。
4.根据权利要求1～3任意一项所述的合成手性1,3-膦醇的方法，其特征在于：所述α,β-不饱和酮类化合物的用量为二苯基膦摩尔量的1～2倍。
5.根据权利要求1～3任意一项所述的合成手性1,3-膦醇的方法，其特征在于：所述铜盐的用量为二苯基膦摩尔量的1％～10％，所述配体的用量为二苯基膦摩尔量的5％～10％，手性双膦双氮钌络合物用量为二苯基膦摩尔量的1％～2％。
6.根据权利要求1～3任意一项所述的合成手性1,3-膦醇的方法，其特征在于：所述无机碱为氢氧化钠、氢氧化钾、磷酸钾、碳酸铯中任意一种，其用量为二苯基膦摩尔量的20％～100％。
7.根据权利要求1～3任意一项所述的合成手性1,3-膦醇的方法，其特征在于：所述有机溶剂为2-甲基四氢呋喃、四氢呋喃、甲基叔丁基醚中任意一种。
8.根据权利要求1～3任意一项所述的合成手性1,3-膦醇的方法，其特征在于：所述水的用量为二苯基膦摩尔量的2～20倍。
9.根据权利要求1～3任意一项所述的合成手性1,3-膦醇的方法，其特征在于：所述氢气氛围中氢气压力为2～10bar。
10.根据权利要求1～3任意一项所述的合成手性1,3-膦醇的方法，其特征在于：所述硼烷的用量为二苯基膦摩尔量的20～40倍。
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