CN111056925A - 一种手性二醇类化合物、手性冠醚类化合物及其制备方法 - Google Patents

一种手性二醇类化合物、手性冠醚类化合物及其制备方法 Download PDF

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CN111056925A
CN111056925A CN201911098430.0A CN201911098430A CN111056925A CN 111056925 A CN111056925 A CN 111056925A CN 201911098430 A CN201911098430 A CN 201911098430A CN 111056925 A CN111056925 A CN 111056925A
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张勇健
萨达拉兹
赵灿
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Shanghai Jiaotong University
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Abstract

本发明公开了一种手性二醇类化合物、手性冠醚类化合物及其制备方法。本发明提供的手性二醇类化合物和手性冠醚类化合物具有四取代立体中心，可广泛应用于手性识别，手性分离技术，且其可作为手性催化剂应用于不对称催化反应制备手性化合物。本发明提供的该类化合物的制备方法是以消旋4‑取代‑4‑乙烯基‑1，3‑二氧戊环‑2‑酮类化合物为原料，在钯源与手性配体配位作用生成的钯配合物和硼化合物为催化剂催化下，与二醇反应制得手性二醇类化合物。本发明提供的制备方法是钯和硼共催化的不对称醚化反应，制备方法催化活性高，区域选择性，非对映选择性和对映选择性高，反应条件温和，反应原料方便易得。

Description

一种手性二醇类化合物、手性冠醚类化合物及其制备方法
技术领域
本发明涉及化工技术领域的化合物及其制备方法，具体涉及一种手性二醇类化合物、手性冠醚类化合物及其制备方法。
背景技术
自从Cram在手性冠醚的开创性的工作以来(Cram,D.J.Am.Chem.Soc.1973,95,2692-2693.)，各种手性冠醚及其具有不同手性单元的衍生物已相继开发出来，并广泛用于手性识别(Wang,C.Chin.J.Org.Chem.2013,33,280-287.)，手性分离技术(Feringa,B.L.Org.Biomol.Chem.2011,9,36-51.)，和相转移催化剂等等(Sala,G.D.Synthesis2018,50,4777-4795.)。众所周知，聚乙二醇是一些碱金属、碱土金属或镧系元素催化下的有机转化和聚合反应的有用配体(Aspinall,H.C.Chem.Rev.2002,102,1807-1850.)，而且手性聚乙二醇类似物也可以作为手性质子源，用于烯醇盐的质子化(Mikami,K.Tetrahedron 1999,55,4595-4620.)。通常，手性冠醚和半冠醚是通过聚乙二醇衍生物对已知的手性二醇进行亲核取代或环化而合成的。至今，直接利用不对称催化方法制备手性聚乙二醇仍未见报道。因此，开发具有新颖结构框架的手性二醇及手性冠醚类化合物具有重要的意义。
在本申请人的公开号为CN107382644A的中国专利中，公开了手性叔醇和叔醚的制备方法，利用消旋4-取代-4-乙烯基-1，3-二氧戊环-2-酮类化合物与水或醇得到手性叔醇和叔醚类化合物。
发明内容
本发明的目的在于针对现有技术中的缺陷，提供一种手性二醇类化合物、手性冠醚类化合物及其制备方法。
本发明的目的是通过以下技术方案来实现的：
本发明第一个方面提供一种手性二醇类化合物I、II、III或IV，所述化合物I、II、III或IV的结构式如下所示：
Figure BDA0002266931040000021
其中：R为氢、C1-C20的烷基、C3-C16的环烷基、C4-C16的含N、O或S的杂环基、C6-C24的芳基、取代基含N、O、S、P或卤素的C6-C24的取代芳基、C6-C26的芳基烷基、-CnH2n-OR1、-CnH2n-SR2或-CnH2n-NR3R4中的一种；其中，n为1～10中任一整数，R1、R2、R3和R4为氢、C1-C8烷基、C4-C15芳基或C5-C15芳基烷基；
R’为-CH2 CH2-(X-CH2CH2)m-或-CH2-Y-CH2-；其中，X为O、S或N-R5；R5为上述R1中的一种；m为0-10000中的任一整数；Y为C1-C20的烷基、C3-C16的环烷基、C4-C16的含N、O或S的杂环基、C6-C24的芳基、取代基含N、O、S、P或卤素的C6-C24的取代芳基、C6-C26的芳基烷基、-CnH2n-OR1、-CnH2n-SR2或-CnH2n-NR3R4中的一种。
本发明第二个方面提供一种手性二醇类化合物I、II、III或IV的制备方法，在有机溶剂中，以钯源与手性配体配位作用生成的钯配合物和硼化合物为催化剂，消旋4-取代-4-乙烯基-1，3-二氧戊环-2-酮类化合物VII和二醇VIII，在0-60℃下反应，得到所述化合物I、II、III或IV；
所述消旋4-取代-4-乙烯基-1，3-二氧戊环-2-酮类化合物VII和所述二醇VIII结构式如下所示：
Figure BDA0002266931040000022
其中：R为氢、C1-C20的烷基、C3-C16的环烷基、C4-C16的含N、O或S的杂环基、C6-C24的芳基、取代基含N、O、S、P或卤素的C6-C24的取代芳基、C6-C26的芳基烷基、-CnH2n-OR1、-CnH2n-SR2或-CnH2n-NR3R4中的一种；其中，n为1～10中任一整数，R1、R2、R3和R4为氢、C1-C8烷基、C4-C15芳基或C5-C15芳基烷基；
R’为-CH2 CH2-(X-CH2CH2)m-或-CH2-Y-CH2-；其中，X为O、S、或N-R5；R5为上述R1中的一种；m为0-10000中的任一整数；Y为C1-C20的烷基、C3-C16的环烷基、C4-C16的含N、O或S的杂环基、C6-C24的芳基、取代基含N、O、S、P或卤素的C6-C24的取代芳基、C6-C26的芳基烷基、-CnH2n-OR1、-CnH2n-SR2或-CnH2n-NR3R4中的一种。
优选地，所述有机溶剂为四氢呋喃、二氧六环、二氯甲烷、三氯甲烷、乙酸乙酯、甲苯、苯、乙醚、甲基叔丁基醚、丙酮、二甲基甲酰胺或乙腈中的一种。
优选地，所述钯源为Pd2(dba)3、Pd2(dba)3·CHCl3、Pd(dba)2、[Pd(allyl)Cl]2、Pd(OAc)2、Pd(CF3COO)2、Pd(CH3CN)2Cl2或Pd(PhCN)2Cl2中的一种。
优选地，所述手性配体为具有如下结构式的手性膦配体中的一种：
Figure BDA0002266931040000031
其中，A为C1-C10的烷基、C6-C16的芳基或C6-C16的取代芳基、OR1或NR2R3，其中R1”为C1-C10的烷基、C6-C16的芳基或C6-C16的取代芳基，R2”、R3”分别为氢、C1-C20的烷基、C6-C20的芳基或C6-C20的取代芳基。
优选地，所述硼化合物的结构式为：
Figure BDA0002266931040000032
其中：R1’、R2’、R3’为C1-C10的烷基、C6-C16的芳基或C6-C16的取代芳基、OR4’中的一种；R4’为氢、C1-C10的烷基、C6-C16的芳基或C6-C16的取代芳基中的一种。
优选地，所述消旋4-取代-4-乙烯基-1，3-二氧戊环-2-酮类化合物VII、所述二醇VIII、所述钯源、所述手性配体及所述硼化合物的摩尔比为1:1-20:0.0001-0.05:0.0001-0.20:0.0001-0.40。
本发明第三个方面提供一种手性冠醚类化合物V或VI，所述化合物V或VI的结构式如下所示：
Figure BDA0002266931040000041
其中：R为氢、C1-C20的烷基、C3-C16的环烷基、C4-C16的含N、O或S的杂环基、C6-C24的芳基、取代基含N、O、S、P或卤素的C6-C24的取代芳基、C6-C26的芳基烷基、-CnH2n-OR1、-CnH2n-SR2或-CnH2n-NR3R4中的一种；其中，n为1～10中任一整数，R1、R2、R3和R4为氢、C1-C8烷基、C4-C15芳基或C5-C15芳基烷基。
本发明第四个方面提供一种手性冠醚类化合物V或VI的制备方法，包括：化合物IX或X为原料，将所述原料与化合物XI，在叔丁醇钾存在下，在四氢呋喃中反应，得到所述化合物V或VI；
其中：所述化合物IX、X和XI的结构式如下：
Figure BDA0002266931040000042
其中：R为氢、C1-C20的烷基、C3-C16的环烷基、C4-C16的含N、O或S的杂环基、C6-C24的芳基、取代基含N、O、S、P或卤素的C6-C24的取代芳基、C6-C26的芳基烷基、-CnH2n-OR1、-CnH2n-SR2或-CnH2n-NR3R4中的一种；其中，n为1～10中任一整数，R1、R2、R3和R4为氢、C1-C8烷基、C4-C15芳基或C5-C15芳基烷基；
B为Cl、Br、I、-OSO2Me或-OSO2C6H4CH3中的一种。
与现有技术相比，本发明具有如下有益效果：
1、本发明所提供的手性二醇类化合物和手性冠醚类化合物是一类具有四取代立体中心的化合物，其结构新颖。可在手性识别、手性分离等领域得到广泛的应用，并可作为手性催化剂应用在不对称催化反应中制备手性化合物。
2、本发明所提供的手性二醇类化合物和手性冠醚类化合物的制备方法，以结构稳定的消旋化合物为原料，与广泛存在、绿色安全的二醇反应，通过金属钯和硼共催化的不对称催化技术，是一种高效的、环境友好的制备方法；其具有如下优点：制备方法具有很好的催化活性；反应的区域选择性和立体选择性高；反应条件温和，反应原料方便易得，具有重要的应用前景。
附图说明
通过阅读参照以下附图对非限制性实施例所作的详细描述，本发明的其它特征、目的和优点将会变得更明显：
图1为本发明一优选实施例的反应式；
图2为本发明一优选实施例中利用不同硼化合物制备手性二醇Ia的结果；
图3为本发明一优选实施例的反应式以及利用不同配体制备手性二醇Ia的结果；
图4为本发明一优选实施例的反应式；
图5为本发明一优选实施例中利用不同溶剂制备手性二醇Ia的结果。
具体实施方式
下面结合具体实施例对本发明进行详细说明。以下实施例将有助于本领域的技术人员进一步理解本发明，但不以任何形式限制本发明。应当指出的是，对本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进。这些都属于本发明的保护范围。
实施例1
本实施例提供一种手性二醇类化合物I，该化合物I的结构式如下：
Figure BDA0002266931040000051
其中：R为氢、C1-C20的烷基、C3-C16的环烷基、C4-C16的含N、O或S的杂环基、C6-C24的芳基、取代基含N、O、S、P或卤素的C6-C24的取代芳基、C6-C26的芳基烷基、-CnH2n-OR1、-CnH2n-SR2或-CnH2n-NR3R4中的一种；其中，n为1～10中任一整数，R1、R2、R3和R4为氢、C1-C8烷基、C4-C15芳基或C5-C15芳基烷基；
R’为-CH2 CH2-(X-CH2CH2)m-或-CH2-Y-CH2-；其中，X为O、S或N-R5；R5为上述R1中的一种；m为0-10000中的任一整数；Y为C1-C20的烷基、C3-C16的环烷基、C4-C16的含N、O或S的杂环基、C6-C24的芳基、取代基含N、O、S、P或卤素的C6-C24的取代芳基、C6-C26的芳基烷基、-CnH2n-OR1、-CnH2n-SR2或-CnH2n-NR3R4中的一种。
上述实施例中的手性二醇类化合物I，可以采用以下方法制备：
反应管中依次加入0.025mmolPd2(dba)3·CHCl3、0.1mmol手性配体3a[X＝N(iPr)]、0.05mmol硼化合物、1.0mmol化合物VIIa、2mmol乙二醇以及5.0mL四氢呋喃，
Figure BDA0002266931040000061
分子筛，20℃下反应16小时。减压蒸去溶剂后残留物柱层析得到相应手性二醇Ia。
参照图1及图2所示，为本实施例的反应式以及利用不同硼化合物制备手性二醇Ia的结果。
实施例2
本实施例提供一种手性二醇类化合物I，该化合物I的结构式如下：
Figure BDA0002266931040000062
其中：R为氢、C1-C20的烷基、C3-C16的环烷基、C4-C16的含N、O或S的杂环基、C6-C24的芳基、取代基含N、O、S、P或卤素的C6-C24的取代芳基、C6-C26的芳基烷基、-CnH2n-OR1、-CnH2n-SR2或-CnH2n-NR3R4中的一种；其中，n为1～10中任一整数，R1、R2、R3和R4为氢、C1-C8烷基、C4-C15芳基或C5-C15芳基烷基；
R’为-CH2 CH2-(X-CH2CH2)m-或-CH2-Y-CH2-；其中，X为O、S或N-R5；R5为上述R1中的一种；m为0-10000中的任一整数；Y为C1-C20的烷基、C3-C16的环烷基、C4-C16的含N、O或S的杂环基、C6-C24的芳基、取代基含N、O、S、P或卤素的C6-C24的取代芳基、C6-C26的芳基烷基、-CnH2n-OR1、-CnH2n-SR2或-CnH2n-NR3R4中的一种。
上述实施例中的手性二醇类化合物I，可以采用以下方法制备：
反应管中依次加入0.0125mmolPd2(dba)3·CHCl3、0.05mmol手性配体、0.025mmol三乙基硼、0.5mmol化合物VIIa、1mmol乙二醇以及2.5mL四氢呋喃，
Figure BDA0002266931040000063
分子筛，20℃下反应16小时。减压蒸去溶剂后残留物柱层析得到相应手性二醇Ia。
与实施例1不同点在于，本实施例进一步给出了利用不同配体进行的制备结果。参照图3所示，为本实施例的反应式以及利用不同配体制备手性二醇Ia的结果。
实施例3
本实施例提供一种手性二醇类化合物I，该化合物I的结构式如下：
Figure BDA0002266931040000071
其中：R为氢、C1-C20的烷基、C3-C16的环烷基、C4-C16的含N、O或S的杂环基、C6-C24的芳基、取代基含N、O、S、P或卤素的C6-C24的取代芳基、C6-C26的芳基烷基、-CnH2n-OR1、-CnH2n-SR2或-CnH2n-NR3R4中的一种；其中，n为1～10中任一整数，R1、R2、R3和R4为氢、C1-C8烷基、C4-C15芳基或C5-C15芳基烷基；
R’为-CH2 CH2-(X-CH2CH2)m-或-CH2-Y-CH2-；其中，X为O、S或N-R5；R5为上述R1中的一种；m为0-10000中的任一整数；Y为C1-C20的烷基、C3-C16的环烷基、C4-C16的含N、O或S的杂环基、C6-C24的芳基、取代基含N、O、S、P或卤素的C6-C24的取代芳基、C6-C26的芳基烷基、-CnH2n-OR1、-CnH2n-SR2或-CnH2n-NR3R4中的一种。
上述实施例中一种手性二醇类化合物I，可以采用以下方法制备，
反应管中依次加入0.05mmolPd2(dba)3·CHCl3、0.2mmol手性配体3a、0.1mmol三乙基硼、2.0mmol化合物VIIa、4mmol乙二醇以及5.0mL溶剂，
Figure BDA0002266931040000072
分子筛，20℃下反应16小时。减压蒸去溶剂后残留物柱层析得到相应手性二醇Ia。
与实施例1不同点在于，本实施例进一步给出了利用不同溶剂进行的制备结果。
参照图4、图5所示，为本实施例的反应式以及利用不同溶剂制备手性二醇Ia的结果。
实施例4
本实施例提供一种手性二醇类化合物I，该化合物I的结构式如下：
Figure BDA0002266931040000073
其中：R为氢、C1-C20的烷基、C3-C16的环烷基、C4-C16的含N、O或S的杂环基、C6-C24的芳基、取代基含N、O、S、P或卤素的C6-C24的取代芳基、C6-C26的芳基烷基、-CnH2n-OR1、-CnH2n-SR2或-CnH2n-NR3R4中的一种；其中，n为1～10中任一整数，R1、R2、R3和R4为氢、C1-C8烷基、C4-C15芳基或C5-C15芳基烷基；
R’为-CH2CH2-(X-CH2CH2)m-或-CH2-Y-CH2-；其中，X为O、S或N-R5；R5为上述R1中的一种；m为0-10000中的任一整数；Y为C1-C20的烷基、C3-C16的环烷基、C4-C16的含N、O或S的杂环基、C6-C24的芳基、取代基含N、O、S、P或卤素的C6-C24的取代芳基、C6-C26的芳基烷基、-CnH2n-OR1、-CnH2n-SR2或-CnH2n-NR3R4中的一种。
上述实施例中手性二醇类化合物I，可以采用以下方法制备：
反应管中依次加入0.1mmolPd2(dba)3·CHCl3、0.4mmol手性配体3a、0.2mmol三乙基硼、4.0mmol化合物VII、8mmol二醇以及5.0mL叔丁基甲基醚，20℃下反应20小时。减压蒸去溶剂后残留物柱层析得到相应手性二醇化合物I，此外手性二醇化合物II是化合物I的对映异构体，在其合成方法中采用构型相反的配体，其他条件与化合物I的实施例一致。
以下是R和R’为不同选择时对应的手性二醇I1HNMR、13CNMR谱图数据，所有化合物可以采用上述实施例1-4中任一种方法制备，相应的产率和对映选择性有一定的差异。
Figure BDA0002266931040000081
Ia:1H NMR(500MHz,CDCl3)δ7.42-7.40(m,2H),7.38-7.35(m,2H),7.30-7.27(m,1H),6.07(dd,J＝17.7,11.0Hz,1H),5.44(dd,J＝11.0,1.2Hz,1H),5.38(dd,J＝17.6,1.2Hz,1H),3.94(d,J＝11.8Hz,1H),3.90(d,J＝11.6Hz,1H),3.76(t,J＝4.5Hz,2H),3.51-3.47(m,1H),3.44-3.40(m,1H),3.08(bs,1H),2.91(bs,1H)；13C NMR(125MHz,CDCl3)δ140.1,137.8,128.3,127.6,126.9,117.8,81.8,66.5,64.5,62.2；HRMS(ESI-MS):Calcd.for C12H16O3(M+Na):231.0997,Found:231.0988；HPLC conditions:Chiralcel OD-Hcolumn,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/19,tminor＝17.56min,tmajor＝19.83min；91％ee.
Figure BDA0002266931040000082
Ib:1H NMR(500MHz,CDCl3)δ7.41-7.39(m,2H),7.38-7.35(m,2H),7.30-7.27(m,1H),6.04(dd,J＝17.6,11.0Hz,1H),5.43(dd,J＝11.0,1.2Hz,1H),5.37(dd,J＝17.7,1.2Hz,1H),3.95(d,J＝11.7Hz,1H),3.92(d,J＝10.6Hz,1H),3.83-3.79(m,2H),3.50(t,J＝5.8Hz,2H),2.63(dd,J＝5.4,5.2,Hz,1H),2.42(dd,J＝6.4,6.4Hz,1H),1.87-1.82(m,2H)；13C NMR(125MHz,CDCl3)δ140.3,138.2,128.3,127.6,126.8,117.5,81.6,66.0,60.9,60.8,32.2；HRMS(ESI-MS):Calcd.for C13H18O3(M+Na):245.1154,Found:245.1148；HPLCconditions:Chiralcel AS-H column,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/9,tminor＝10.37min,tmajor＝11.46min；96％ee.
Figure BDA0002266931040000091
Ic:1H NMR(500MHz,CDCl3)δ7.40-7.38(m,2H),7.37-7.35(m,2H),7.30-7.27(m,1H),6.07(dd,J＝17.7,11.0Hz,1H),5.45(dd,J＝11.0,1.2Hz,1H),5.39(dd,J＝17.6,1.2Hz,1H),3.89(d,J＝11.4Hz,1H),3.86(d,J＝11.4Hz,1H),3.66(t,J＝6.0Hz,2H),3.40-3.33(m,2H),2.30(bs,2H),1.73-1.64(m,4H)；13C NMR(125MHz,CDCl3)δ140.2,137.6,128.3,127.6,126.9,117.8,81.8,66.9,62.8,62.7,29.7,26.9；HRMS(ESI-MS):Calcd.forC14H20O3(M+Na):259.1310,Found:259.1307；HPLC conditions:Chiralcel AS-H column,220nm,flow rate:0.6ml/min,i-PrOH/hexanes＝1/9,tmajor＝22.27min,tminor＝23.62min；93％ee.
Figure BDA0002266931040000092
Id:1H NMR(500MHz,CDCl3)δ7.41-7.39(m,2H),7.37-7.34(m,2H),7.30-7.26(m,1H),6.07(dd,J＝17.6,11.0Hz,1H),5.39(dd,J＝11.1,1.2Hz,1H),5.33(dd,J＝17.6,1.2Hz,1H),3.96(d,J＝11.8,Hz,1H),3.93(d,J＝11.8,Hz,1H),3.76(t,J＝4.4,Hz,2H),3.73-3.66(m,2H),3.63(t,J＝4.8,Hz,2H),3.58-3.54(m,1H),3.51-3.47(m,1H),3.32(bs,1H)3.00(bs,1H)；13C NMR(125MHz,CDCl3)δ140.3,138.4,128.2,127.5,126.8,117.3,82.0,72.6,70.7,65.9,62.7,61.6；HRMS(ESI-MS):Calcd.for C14H20O4(M+Na):275.1259,Found:275.1260；HPLC conditions:Chiralcel OD-H column,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/19,tminor＝28.90min,tmajor＝33.38min；96％ee.
Figure BDA0002266931040000093
Ie:1H NMR(400MHz,CDCl3)δ7.39-7.36(m,2H),7.35-7.32(m,2H),7.28-7.24(m,1H),6.07(dd,J＝17.5,11.0Hz,1H),5.31(dd,J＝11.0,1.2Hz,1H),5.23(dd,J＝17.0,1.2Hz,1H),4.37(bs,1H),4.25(bs,1H),4.01(d,J＝12.3Hz,1H),3.98(d,J＝12.2Hz,1H),3.71-3.66(m,8H),3.61-3.57(m,3H),3.50-3.46(m,1H)；13C NMR(125MHz,CDCl3)δ140.9,139.5,128.1,127.3,126.7,116.5,82.0,73.1,70.9,70.5,69.7,64.7,62.7,61.6；HRMS(ESI-MS):Calcd.for C16H24O5(M+Na):319.1521,Found:319.1528；HPLC conditions:Chiralcel AS-H column,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/13,tmajor＝18.22,tminor＝20.49min；96％ee.
Figure BDA0002266931040000101
If:1H NMR(500MHz,CDCl3)δ7.69(d,J＝8.3Hz,2H),7.40-7.35(m,4H),7.31-7.28(m,3H),6.10(dd,J＝17.7,11.0Hz,1H),5.49(dd,J＝11.1,1.2Hz,1H),5.39(dd,J＝17.8,1.2Hz,1H),3.90(d,J＝11.8Hz,1H),3.84(d,J＝11.8Hz,1H),3.81(t,J＝4.0Hz,1H),3.62-3.52(m,2H),3.34-3.32(m,2H),3.30-3.28(m,2H),2.70(bs,1H),2.42(s,3H),1.89(bs,1H)；13C NMR(125MHz,CDCl3)δ143.6,139.3,136.7,135.4,129.7,128.4,127.8,127.3,127.0,118.7,82.9,67.4,63.0,61.4,53.0,50.3,21.4；HRMS(ESI-APCI):Calcd.forC11H27NO5S(M+Na):428.1508,Found:428.1505；HPLC conditions:Chiralcel OJ-H column,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/2,tminor＝28.39min,tmajor＝33.97min；91％ee.
Figure BDA0002266931040000102
Ig:1H NMR(500MHz,CDCl3)δ7.41-7.39(m,2H),7.38-7.35(m,2H),7.31-7.28(m,1H),6.11(dd,J＝17.6,11.0Hz,1H),5.79-5.70(m,2H),5.48(dd,J＝11.0,1.2Hz,1H),5.40(dd,J＝17.6,1.2Hz,1H),4.13(d,J＝12.0Hz,1H),4.09(d,J＝12.0Hz,1H),3.97-3.82(m,4H)2.44(bs,2H)；13C NMR(125MHz,CDCl3)δ139.8,137.1,131.4,128.6,128.3,127.7,127.0,118.2,82.5,67.4,59.4,58.4；HRMS(ESI-MS):Calcd.for C14H18O3(M+Na):257.1154,Found:257.1161；HPLC conditions:Chiralcel AS-H column,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/4,tminor＝6.81min,tmajor＝7.60min；85％ee.
Figure BDA0002266931040000103
Ih:1H NMR(500MHz,CDCl3)δ7.42-7.40(m,2H),7.39-7.36(m,2H),7.32-7.29(m,1H),6.11(dd,J＝17.7,11.1Hz,1H),5.50(dd,J＝11.1,1.2Hz,1H),5.43(dd,J＝17.6,1.2Hz,1H),4.29(s,2H),4.11(d,J＝15.3Hz,1H),4.02(d,J＝15.4Hz,1H),3.92–3.85(m,2H),2.34(bs,1H),1.89(bs,1H)；13C NMR(125MHz,CDCl3)δ139.2,136.5,128.4,127.9,127.0,118.9,84.3,83.4,82.4,67.7,52.4,51.0；HRMS(ESI-MS):Calcd.for C14H16O3(M+Na):255.0997,Found:255.0973；HPLC conditions:Chiralcel OJ-H column,220nm,flowrate:1ml/min,i-PrOH/hexanes＝1/6,tmajor＝32.48min,tminor＝34.90min；89％ee.
Figure BDA0002266931040000111
Ii:1H NMR(500MHz,CDCl3)δ7.46-7.44(m,2H),7.40-7.37(m,3H),7.34-7.31(m,2H),7.30-7.28(m,2H),6.19(dd,J＝17.6,11.0Hz,1H),5.52(dd,J＝11.0,1.2Hz,1H),5.45(dd,J＝17.7,1.2Hz,1H),4.70(d,J＝12.1Hz,1H),4.67(d,J＝12.2Hz,1H),4.52(d,J＝10.7Hz,1H),4.45(d,J＝10.6Hz,1H),3.97(d,J＝11.6Hz,1H),3.94(d,J＝11.8Hz,1H),3.16(bs,1H),2.55(bs,1H)；13C NMR(125MHz,CDCl3)δ139.9,139.7,137.3,136.6,129.8,129.7,128.5,128.4,128.2,127.8,127.0,118.6,83.0,67.0,64.4,63.7；HRMS(ESI-MS):Calcd.for C18H20O3(M+Na):307.1310,Found:307.1309；HPLC conditions:Chiralcel AD-Hcolumn,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/13,tminor＝27.19min,tmajor＝29.24min；83％ee.
Figure BDA0002266931040000112
Ij:1H NMR(500MHz,CDCl3)δ7.48-7.45(m,2H),7.40-7.31(m,5H),7.30-7.27(m,2H),6.18(dd,J＝17.7,11.0Hz,1H),5.52(dd,J＝11.1,1.2Hz,1H),5.48(dd,J＝17.8,1.2Hz,1H),4.68(s,2H),4.43(d,J＝11.4Hz,1H),4.38(d,J＝11.4Hz,1H),3.96-3.89(m,2H),2.13(bs,1H),1.73(bs,1H)；13C NMR(125MHz,CDCl3)δ141.0,139.9,139.0,137.2,128.6,128.4,127.8,127.0,126.6,126.0,125.9,118.4,82.5,67.6,65.2,65.1；HRMS(ESI-MS):Calcd.for C18H20O3(M+Na):307.1310,Found:307.1307；HPLC conditions:ChiralcelOD-Hcolumn,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/13,tmajor＝33.86min,tminor＝37.82min；91％ee.
Figure BDA0002266931040000113
Ik:1H NMR(500MHz,CDCl3)δ7.48-7.46(m,2H),7.40-7.34(m,6H),7.33-7.30(m,1H),6.18(dd,J＝17.6,11.1Hz,1H),5.52(dd,J＝11.2,1.2Hz,1H),5.49(dd,J＝17.8,1.2Hz,1H),4.68(s,2H),4.43(d,J＝11.4Hz,1H),4.38(d,J＝11.4Hz,1H),3.97-3.89(m,2H),2.04(dd,J＝6.6,6.2Hz,1H),1.80(dd,J＝5.8,5.4Hz,1H)；13C NMR(125MHz,CDCl3)δ140.1,140.0,138.1,137.3,128.4,127.8,127.6,127.1,127.0,118.4,82.5,67.6,65.1,65.0；HRMS(ESI-MS):Calcd.for C18H20O3(M+Na):307.1310,Found:307.1326；HPLCconditions:Chiralcel OD-H column,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/13,tminor＝46.46min,tmajor＝50.48min；95％ee.
Figure BDA0002266931040000121
Il:1H NMR(500MHz,CDCl3)δ7.70(t,J＝7.8Hz,1H),7.47–7.45(m,2H),7.38–7.35(m,2H),7.31–7.28(m,2H),7.23(d,J＝7.8Hz,1H),6.14(dd,J＝17.6,11.0Hz,1H),5.42(dd,J＝11.2,1.3Hz,1H),5.38(dd,J＝17.6,1.2Hz,1H),4.73(s,2H),4.58(d,J＝13.4Hz,1H),4.51(d,J＝13.4Hz,1H),4.07(d,J＝12.0Hz,1H),4.04(d,J＝12.0Hz,1H)；13C NMR(125MHz,CDCl3)δ159.2,157.9,140.4,138.5,137.6,128.4,127.6,126.9,120.2,119.6,117.5,83.2,66.2,66.0,64.4；HRMS(ESI-MS):Calcd.for C17H19NO3(M+Na):308.1263,Found:308.1275；HPLC conditions:Chiralcel AD-H column,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/4,tmajor＝8.09min,tminor＝9.01min；96％ee.
Figure BDA0002266931040000122
Im:1H NMR(500MHz,CDCl3)δ7.29(d,J＝8.2Hz,2H),7.17(d,J＝8.0Hz,2H),6.06(dd,J＝17.6,11.0Hz,1H),5.43(dd,J＝11.0,1.2Hz,1H),5.38(dd,J＝17.6,1.3Hz,1H),3.92(d,J＝11.2Hz,1H),3.87(d,J＝11.4Hz,1H),3.75(t,J＝4.4Hz,2H),3.48-3.44(m,1H)3.41-3.38(m,1H),3.23(bs,1H)2.96(bs,1H),2.34(s,3H)；13C NMR(125MHz,CDCl3)δ137.9,137.3,137.0,129.0,126.9,117.6,81.8,66.6,64.4,62.2,21.0；HRMS(ESI-MS):Calcd.forC13H18O3(M+Na):245.1154,Found:245.1156；HPLC conditions:Chiralcel AD-H column,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/9,tminor＝8.44min,tmajor＝9.50min；89％ee.
Figure BDA0002266931040000131
In:1H NMR(400MHz,CDCl3)δ7.52(dd,J＝7.8,1.6Hz,1H),7.30-7.26(m,1H),7.00-6.96(m,1H),6.90(dd,J＝8.2,1.2Hz,1H),6.10(dd,J＝17.7Hz,11.0,1H),5.29(dd,J＝10.9,1.3Hz,1H),5.20(dd,J＝17.7,1.4Hz,1H),4.18(d,J＝11.6,Hz,1H),4.02(d,J＝11.6,Hz,1H),3.78(s,3H),3.77–3.72(m,2H),3.53(t,J＝4.5Hz,2H),3.27(bs,1H),2.79(bs,1H)；13C NMR(126MHz,CDCl3)δ156.8,137.8,129.0,128.7,128.5,120.6,116.3,111.8,81.6,64.3,64.2,62.2,55.2；HRMS(ESI-MS):Calcd.for C13H18O4(M+Na):261.1103,Found:261.1100；HPLC conditions:Chiralcel AD-H column,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/11,tminor＝14.30min,tmajor＝16.25min；92％ee.
Figure BDA0002266931040000132
Io:1H NMR(500MHz,CDCl3)δ7.27(d,J＝8.4Hz,1H),7.00-6.96(m,2H),6.84-6.82(m,1H),6.05(dd,J＝17.7,11.0Hz,1H),5.44(dd,J＝12.2,1.2Hz,1H),5.39(dd,J＝17.7,1.2Hz,1H),3.93(d,J＝11.7Hz,1H),3.90(d,J＝11.2Hz,1H),3.80(s,3H),3.77(t,J＝4.4Hz,2H),3.53-3.49(m,1H),3.47-3.43(m,1H),3.01(bs,1H),2.78(bs,1H)；13C NMR(125MHz,CDCl3)δ159.6,141.9,137.7,129.4,119.2,117.8,113.1,112.7,81.8,66.4,64.5,62.3,55.2；HRMS(ESI-MS):Calcd.for C13H18O4(M+Na):261.1103,Found:261.1101；HPLC conditions:Chiralcel AD-H column,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/9,tminor＝11.47min,tmajor＝12.58min；90％ee.
Figure BDA0002266931040000133
Ip:1H NMR(500MHz,CDCl3)δ7.33(d,J＝8.8Hz,2H),6.90(d,J＝8.8Hz,2H),6.05(dd,J＝17.1,10.5Hz,1H),5.43(dd,J＝11.0,1.2Hz,1H),5.38(dd,J＝17.6,1.2Hz,1H),3.94(d,J＝11.6Hz,1H),3.88(d,J＝11.6Hz,1H),3.80(s,3H),3.76(d,J＝4.7Hz,2H),3.48–3.44(m,1H),3.43–3.39(m,1H),1.76(bs,2H)；13C NMR(100MHz,CDCl3)δ159.0,138.1,131.9,128.2,117.5,113.8,81.5,66.4,64.3,62.3,55.2；HRMS(ESI-MS):Calcd.forC13H18O4(M+Na):261.1205,Found:261.1100；HPLC conditions:Chiralcel OD-H column,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/9,tminor＝11.99min,tmajor＝15.64min；93％ee.
Figure BDA0002266931040000141
Iq:1H NMR(500MHz,CDCl3)δ7.41-7.37(m,2H),7.07-7.02(m,2H),6.04(dd,J＝17.8,11.1Hz,1H),5.45(dd,J＝11.1,1.1Hz,1H),5.36(dd,J＝17.7,1.2Hz,1H),3.94-3.86(m,2H),3.77(t,J＝5.2Hz,2H),3.50-3.46(m,1H),3.44-3.40(m,1H),3.03(bs,1H),2.94(dd,J＝6.4,6.5Hz,1H)；13C NMR(125MHz,CDCl3)δ163.1,161.2,137.7,136.0,135.9,128.8,128.7,118.0,115.2,115.0,81.5,66.4,64.5,62.2；HRMS(ESI-MS):Calcd.forC12H15FO3(M+Na):249.0903,Found:249.0903；HPLC conditions:Chiralcel AS-Hcolumn,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/4,tminor＝4.89min,tmajor＝6.83min；88％ee.
Figure BDA0002266931040000142
Ir:1H NMR(500MHz,CDCl3)δ7.36(d,J＝8.8Hz,2H),7.33(d,J＝8.9Hz,2H),6.02(dd,J＝17.8,11.1Hz,1H),5.45(dd,J＝10.0,1.0Hz,1H),5.34(dd,J＝17.6,1.0Hz,1H),3.90(d,J＝11.8Hz,1H),3.85(d,J＝11.7Hz,1H),3.79-3.74(m,2H),3.50-3.46(m,1H),3.43-3.39(m,1H),3.13(bs,2H)；13C NMR(125MHz,CDCl3)δ138.8,137.4,133.5,128.4,118.3,81.5,77.2,66.3,64.5,62.2；HRMS(ESI-MS):Calcd.for C12H15ClO3(M+Na):265.0607,Found:265.0609；HPLC conditions:Chiralcel AD-H column,220 nm,flowrate:1ml/min,i-PrOH/hexanes＝1/9,tminor＝8.95min,tmajor＝10.16min；86％ee.
Figure BDA0002266931040000143
Is:1H NMR(500MHz,CDCl3)δ7.48(d,J＝8.6Hz,2H),7.29(d,J＝8.6Hz,2H),6.02(dd,J＝17.8,11.1Hz,1H),5.45(dd,J＝11.0,1.0Hz,1H),5.34(dd,J＝17.8,1.1Hz,1H),3.90(d,J＝11.9Hz,1H),3.85(d,J＝11.6Hz,1H),3.76(t,J＝4.4Hz,2H),3.50-3.47(m,1H),3.43-3.39(m,1H),3.17(bs,1H),3.12(dd,J＝6.6,6.4Hz,1H)；13C NMR(125MHz,CDCl3)δ139.4,137.4,131.4,128.8,121.7,118.3,81.6,66.3,64.5,62.2；HRMS(ESI-MS):Calcd.for C12H15BrO3(M+Na):309.0102,Found:309.0114；HPLC conditions:ChiralcelAD-H column,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/9,tminor＝9.06min,tmajor＝10.39min；90％ee.
Figure BDA0002266931040000151
It:1H NMR(500MHz,CDCl3)δ6.93(d,J＝1.7Hz,1H),6.86(dd,J＝8.2,1.8Hz,1H),6.79(d,J＝8.2Hz,1H),6.02(dd,J＝17.6,11.0Hz,1H),5.95(s,2H),5.43(dd,J＝11.0,1.2Hz,1H),5.38(dd,J＝17.7,1.2Hz,1H),3.89(d,J＝11.6Hz,1H),3.86(d,J＝11.7Hz,1H),3.76(t,J＝4.6Hz,2H),3.50-3.46(m,1H),3.43-3.39(m,1H),3.08(bs,1H),2.89(bs,1H)；13C NMR(125MHz,CDCl3)δ147.8,147.0,137.9,134.0,120.2,117.7,107.9,107.7,101.0,81.6,66.4,64.4,62.2；HRMS(ESI-MS):Calcd.for C13H16O5(M+Na):275.0895,Found:275.0893；HPLC conditions:Chiralcel AS-H column,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/4,tminor＝8.16min,tmajor＝11.54min；75％ee.
Figure BDA0002266931040000152
Iu:1H NMR(500MHz,CDCl3)δ7.54(dd,J＝2.2,0.9Hz,1H),7.43-7.41(dd,J＝8.4,0.9Hz,1H),7.27-7.24(m,1H),5.98(dd,J＝17.8,11.0Hz,1H),5.47(dd,J＝12.0,1.0Hz,1H),5.34(dd,J＝18.7,1.0Hz,1H),3.94(d,J＝11.8Hz,1H),3.82(d,J＝13.2Hz,1H),3.79(t,J＝6.0Hz,2H),3.55-3.50(m,1H),3.47-3.44(m,1H),3.17(bs,1H),3.04(bs,1H)；13CNMR(125MHz,CDCl3)δ141.1,137.1,132.4,131.6,130.2,129.1,126.4,118.7,81.2,66.0,64.6,62.2；HRMS(ESI-MS):Calcd.for C12H14Cl2O3(M+Na):299.0218,Found:299.0215；HPLCconditions:Chiralcel AD-H column,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/6,tminor＝5.80min,tmajor＝6.72min；89％ee.
Figure BDA0002266931040000153
Iv:1H NMR(500MHz,CDCl3)δ7.86-7.80(m,4H),7.51(dd,J＝8.6,1.8Hz,1H),7.49-7.46(m,2H),6.13(dd,J＝17.6,11.0Hz,1H),5.47(dd,J＝11.0,1.2Hz,1H),5.42(dd,J＝17.6,1.2Hz,1H),4.06(d,J＝11.6Hz,1H),4.00(d,J＝11.7Hz,1H),3.78(t,J＝4.5Hz,2H),3.53-3.44(m,2H),3.16(bs,1H),2.97(bs,1H)；13C NMR(125MHz,CDCl3)δ137.9,137.6,133.0,132.7,128.2,128.0,127.5,126.2,126.1,125.9,124.9,118.0,81.9,66.2,64.6,62.3；HRMS(ESI-MS):Calcd.for C16H18O3(M+Na):281.1154,Found:281.1150；HPLCconditions:Chiralcel AS-H column,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/9,tminor＝10.81min,tmajor＝12.28min；86％ee.
Figure BDA0002266931040000161
Iw:1H NMR(500MHz,CDCl3)δ7.32(dd,J＝5.0,3.0Hz,1H),7.27(dd,J＝3.0,1.4Hz,1H),7.08(dd,J＝5.0,1.4Hz,1H),6.09(dd,J＝17.6,11.0Hz,1H),5.43(dd,J＝11.0,1.2Hz,1H),5.39(dd,J＝17.5,1.2Hz,1H),3.94(dd,J＝11.6,5.4Hz,1H),3.82(dd,J＝11.6,6.4Hz,1H),3.73(t,J＝4.8Hz,2H),3.48-3.44(m,1H),3.40-3.36(m,1H),3.16(dd,J＝5.4,5.2Hz,1H),3.02(dd,J＝6.4,6.3Hz,1H)；13C NMR(125MHz,CDCl3)δ141.4,137.4,126.9,125.8,123.0,117.7,80.5,67.0,64.6,62.2；HRMS(ESI-MS):Calcd.for C10H14O3S(M+Na):237.0561,Found:237.0567；HPLC conditions:Chiralcel AS-H column,220nm,flowrate:1ml/min,i-PrOH/hexanes＝1/9,tminor＝8.68min,tmajor＝12.43min；70％ee.
Figure BDA0002266931040000162
Ix:1H NMR(400MHz,CDCl3)δ7.35-7.30(m,2H),7.26-7.22(m,2H),5.90(dd,J＝17.6,11.0Hz,1H),5.34(dd,J＝4.6,1.2Hz,1H),5.30(dd,J＝11.0,1.2Hz,1H),4.62(s,2H),4.39(s,2H),3.54(d,J＝11.2Hz,1H),3.47(d,J＝11.3Hz,1H),2.36(bs,2H),1.38(s,3H)；13C NMR(126MHz,CDCl3)δ141.1,139.6,139.2,128.5,126.7,126.1,126.0,117.2,78.5,69.4,65.0,64.8,18.5；HRMS(ESI-MS):Calcd.for C13H18O3(M+Na):245.1154,Found:245.1158；HPLC conditions:Chiralcel OD-H column,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/6,tminor＝10.57min,tmajor＝12.12min；41％ee.
实施例5
本实施例提供一种手性二醇类化合物III，该化合物III其结构式如下：
Figure BDA0002266931040000171
反应管中依次加入Pd2(dba)3·CHCl3(0.03mmol)、手性配体3a(0.12mmol)、三乙基硼(0.05mmol)、化合物VII(2.2mmol)、二醇(1mmol)以及叔丁基甲基醚(5.0mL),20℃下反应36小时。减压蒸去溶剂后残留物柱层析得到相应手性二醇类化合物III,此外手性二醇化合物IV是化合物III的对映异构体，在其合成方法中采用构型相反的配体，其他条件与化合物III的实施例一致。
以下是R和R’为不同选择时对应的手性二醇类化合物III1HNMR、13CNMR谱图数据，所有化合物可以利用实施例1-5的任意一种方法制备，相应的产率和对映选择性有一定的差异。
Figure BDA0002266931040000172
IIIa:HPLC analysis indicated 6:1dr；1H NMR(500MHz,CDCl3)δ7.45-7.42(m,4H),7.38-7.35(m,4H),7.31-7.27(m,2H),6.10(dd,J＝17.6,11.0Hz,2H),5.43(dd,J＝11.0,1.2Hz,2H),5.40(dd,J＝17.8,1.5Hz,2H),3.99(d,J＝11.8Hz,2H),3.94(d,J＝11.8Hz,2H),3.59-3.50(m,4H),2.99(bs,2H)；13C NMR(125MHz,CDCl3)δ140.0,138.0,128.3,127.6,126.9,117.6,82.3,66.5,63.0；HRMS(ESI-MS):Calcd.for C22H26O4(M+NH4):372.2175,Found:372.2186；HPLC conditions:Lux 5u Cellulose-2,220nm,flow rate:0.5ml/min,i-PrOH/hexanes＝1/9,tminor＝28.58min,tmajor＝42.80min；97％ee.
Figure BDA0002266931040000173
IIIb:HPLC analysis indicated 9:1dr；1H NMR(500MHz,CDCl3)δ7.40–7.38(m,4H),7.36–7.34(m,4H),7.30–7.26(m,2H),6.07(dd,J＝17.7,11.0Hz,2H),5.43(dd,J＝11.0,1.4Hz,2H),5.37(d,J＝17.6,1.3Hz,2H),3.91(d,J＝10.6Hz,2H),3.89(d,J＝8.6Hz,2H),3.54–3.47(m,4H),2.42(bs,2H),1.92–1.87(m,2H)；13C NMR(125MHz,CDCl3)δ140.4,138.0,128.3,127.6,126.9,117.6,81.8,66.7,59.8,30.6；HRMS(ESI-MS):Calcd.forC23H28O4(M+NH4):386.2331,Found:386.2349；HPLC conditions:Chiralcel AD-H column,220nm,flow rate:0.5ml/min,i-PrOH/hexanes＝1/9,tminor＝46.75min,tmajor＝49.0min；99％ee.
Figure BDA0002266931040000181
IIIc:HPLC analysis indicated 15:1 dr；1H NMR(500MHz,CDCl3)δ7.40-7.34(m,8H),7.30-7.27(m,2H),6.06(dd,J＝17.7,11.0Hz,2H),5.44(dd,J＝11.0,1.3Hz,2H),5.38(dd,J＝17.6,1.3Hz,2H),3.89-3.83(m,4H),3.37-3.31(m,4H),2.08(dd,J＝5.8,5.2Hz,2H),1.74-1.69(m,4H)；13C NMR(125MHz,CDCl3)δ140.4,137.7,128.3,127.6,126.9,117.7,81.6,67.0,62.8,27.0；HRMS(ESI-MS):Calcd.for C24H30O4(M+NH4):400.2488,Found:400.2509；HPLC conditions:Chiralcel OJ-H column,220nm,flow rate:0.5ml/min,i-PrOH/hexanes＝1/1.5,tmajor＝17.28min,tminor＝24.07min；>99％ee.
Figure BDA0002266931040000182
IIId:HPLC analysis indicated 16:1 dr；1H NMR(500MHz,CDCl3)δ7.42-7.39(m,4H),7.36-7.32(m,4H),7.29-7.25(m,2H),6.14(dd,J＝17.4,11.0Hz,2H),5.39(dd,J＝10.9,8.6Hz,2H),5.30(dd,J＝17.6,5.7Hz,2H),4.46(dd,J＝7.3,6.7Hz,2H),3.97-3.87(m,4H),3.74-3.67(m,4H),3.63-3.57(m,2H),3.50-3.44(m,2H)；13C NMR(125MHz,CDCl3)δ140.5,138.4,128.2,127.4,127.0,117.3,82.5,70.9,66.3,62.5；HRMS(ESI-MS):Calcd.forC24H30O5(M+NH4):416.2437,Found:416.2452；HPLC conditions:Chiralcel AS-Hcolumn,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/19,tmajor＝44.53min；>99％ee.
Figure BDA0002266931040000183
IIIe:HPLC analysis indicated 12:1 dr；1H NMR(400MHz,CDCl3)δ7.40-7.38(m,4H),7.33(t,J＝7.4Hz,4H),7.27-7.24(m,2H),6.07(dd,J＝17.6,11.0Hz,2H),5.35(dd,J＝11.0,1.2Hz,2H),5.29(dd,J＝19.1,1.4Hz,2H),3.92(s,4H),3.71(s,4H),3.70-3.67(m,4H),3.58-3.54(m,4H),3.50-3.46(m,2H)；13C NMR(125MHz,CDCl3)δ140.8,138.8,128.1,127.3,126.9,117.0,82.0,71.0,70.5,65.7,62.8；HRMS(ESI-MS):Calcd.for C26H34O6(M+NH4):460.2699,Found:460.2715；HPLC conditions:Chiralcel OD-H column,220 nm,flow rate:1ml/min,i-PrOH/hexanes＝1/19,tmajor＝51.16min；>99％ee.
Figure BDA0002266931040000184
IIIf:HPLC analysis indicated 9:1 dr；1H NMR(500MHz,CDCl3)δ7.68(d,J＝8.2Hz,2H),7.36–7.32(m,8H),7.30–7.25(m,4H),6.03(dd,J＝17.7,11.0Hz,2H),5.43(dd,J＝11.0,1.3Hz,2H),5.34(dd,J＝17.5,1.2Hz,2H),3.82(d,J＝11.6Hz,2H),3.78(d,J＝11.8Hz,2H),3.55–3.46(m,4H),3.43–3.40(m,4H),2.48(bs,2H),2.40(s,3H)；13C NMR(125MHz,CDCl3)δ143.4,139.7,136.9,136.4,129.6,128.3,127.7,127.3,127.0,118.4,82.6,67.3,62.0,49.2,21.4；HRMS(ESI-APCI):Calcd.for C31H37NO6S(M+NH4):569.2685,Found:569.2715；HPLC conditions:Lux 5u Cellulose-2,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/4,tminor＝11.82min,tmajor＝29.75min；99％ee.
Figure BDA0002266931040000191
IIIg:HPLC analysis indicated 10:1 dr；1H NMR(500MHz,CDCl3)δ7.38-7.32(m,8H),7.30-7.27(m,2H),6.08(dd,J＝17.6,11.0Hz,2H),5.79-5.73(m,2H),5.44(dd,J＝11.0,1.4Hz,2H),5.37(dd,J＝17.6,1.4Hz,2H),3.90-3.80(m,8H),2.15(dd,J＝6.5,6.5Hz,2H)；13C NMR(125MHz,CDCl3)δ139.9,137.1,129.0,128.3,127.7,127.0,118.2,82.5,67.7,59.8；HRMS(ESI-MS):Calcd.for C24H28O4(M+NH4):398.2331,Found:398.2348；HPLCconditions:Lux 5u Cellulose-2,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/9,tminor＝22.98min,tmajor＝38.06min；>99％ee.
Figure BDA0002266931040000192
IIIh:HPLC analysis indicated 14:1 dr；1H NMR(500MHz,CDCl3)δ7.42-7.36(m,8H),7.32-7.29(m,2H),6.12(dd,J＝17.7,11.0Hz,2H),5.50(dd,J＝11.0,11Hz,2H),5.42(dd,J＝17.6,17.6Hz,2H),4.12(d,J＝14.2Hz,2H),4.03(d,J＝14.6Hz,2H),3.92-3.84(m,4H),2.24(dd,J＝6.8,6.7Hz,2H)；13C NMR(125MHz,CDCl3)δ139.3,136.6,128.4,127.9,127.0,118.8,83.4,82.7,67.8,52.4；HRMS(ESI-MS):Calcd.for C24H26O4(M+NH4):396.2175,Found:396.2195；HPLC conditions:Lux 5u Cellulose-2,220 nm,flow rate:1ml/min,i-PrOH/hexanes＝1/3,tminor＝13.35min,tmajor＝23.31min；>99％ee.
Figure BDA0002266931040000201
IIIi:HPLC analysis indicated 5:1 dr；1H NMR(500MHz,CDCl3)δ7.45–7.40(m,6H),7.37–7.34(m,4H),7.33–7.28(m,4H),6.12(dd,J＝17.6,11.0Hz,2H),5.46(dd,J＝11.0,1.4Hz,2H),5.42(dd,J＝17.8,1.2Hz,2H),4.48(d,J＝11.5Hz,2H),4.44(d,J＝11.6Hz,2H),3.95–3.88(m,4H),2.25(bs,2H)；13C NMR(125MHz,CDCl3)δ140.0,137.6,136.7,128.6,128.4,127.8,127.7,127.0,118.1,82.7,67.2,63.3；HRMS(ESI-MS):Calcd.for C28H30O4(M+NH4):448.2488,Found:448.2509；HPLC conditions:Lux 5uCellulose-2,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/4,tmjnor＝6.85min,tmajor＝14.39min；98％ee.
Figure BDA0002266931040000202
IIIj:HPLC analysis indicated 11:1 dr；1H NMR(500MHz,CDCl3)δ7.49–7.47(m,4H),7.40–7.29(m,10H),6.18(dd,J＝17.6,11.1Hz,2H),5.52(dd,J＝8.4,8.4Hz,2H),5.49(dd,J＝15.0,15.0Hz,2H),4.45(d,J＝11.6Hz,2H),4.40(d,J＝11.6Hz,2H),3.98–3.90(m,4H),2.05(dd,J＝6.7,6.4Hz,2H)；13C NMR(125MHz,CDCl3)δ140.0,138.9,137.3,128.5,128.4,127.8,127.0,126.4,126.2,118.4,82.5,67.6,65.2；HRMS(ESI-MS):Calcd.forC28H30O4(M+NH4):448.2488,Found:448.2508；HPLC conditions:Lux 5u Cellulose-2,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/3,tmajor＝14.76min；>99％ee.
Figure BDA0002266931040000203
IIIk:HPLC analysis indicated 12:1 dr；1H NMR(500MHz,CDCl3)δ7.48–7.46(m,4H),7.40–7.36(m,8H),7.32–7.29(m,2H),6.18(dd,J＝17.6,11.1Hz,2H),5.51(dd,J＝8.6,1.2Hz,2H),5.48(dd,J＝16.3,1.2Hz,2H),4.43(d,J＝11.4Hz,2H),4.38(d,J＝11.4Hz,2H),3.97–3.89(m,4H),2.04(dd,J＝5.8,5.7Hz,2H)；13C NMR(125MHz,CDCl3)δ140.0,137.9,137.3,128.4,127.7,127.4,127.0,118.3,82.4,77.2,67.6,65.0；HRMS(ESI-MS):Calcd.for C28H30O4(M+NH4):448.2488,Found:448.2509；HPLC conditions:Lux5uCellulose-2,220 nm,flow rate:1ml/min,i-PrOH/hexanes＝1/4,tminor＝13.27min,tmajor＝40.63min；>99％ee.
Figure BDA0002266931040000211
IXa:HPLC analysis indicated 15:1 dr；1H NMR(400MHz,CDCl3)δ7.65(t,J＝7.7Hz,1H),7.48-7.45(m,4H),7.38-7.34(m,4H),7.30-7.26(m,2H),7.14(d,J＝7.7Hz,2H),6.20(dd,J＝17.6,11.0Hz,2H),6.06(bs,2H),5.40(dd,J＝10.8,1.0Hz,2H),5.35(dd,J＝17.6,1.2Hz,2H),4.62(d,J＝13.7Hz,2H),4.50(d,J＝13.8Hz,2H),4.08-3.99(m,4H)；13C NMR(125MHz,CDCl3)δ158.3,140.5,138.2,137.6,128.2,127.4,127.0,120.4,117.7,83.8,66.7,65.9；HRMS(ESI-MS):Calcd.for C27H29NO4(M+H):432.2175,Found:432.2192；HPLC conditions:Lux 5u Cellulose-2,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/2.3,tminor＝9.48min,tmajor＝22.92min；>99％ee.
Figure BDA0002266931040000212
IIIm:HPLC analysis indicated 5:1 dr；1H NMR(500MHz,CDCl3)δ7.30(d,J＝8.1Hz,4H),7.17(d,J＝8.0Hz,4H),6.08(dd,J＝17.6,11.0Hz,2H),5.40(dd,J＝7.9,1.2Hz,2H),5.38(dd,J＝14.6,1.4Hz,2H),3.98(d,J＝11.6Hz,2H),3.90(d,J＝11.6Hz,2H),3.57–3.44(m,4H),2.96(dd,J＝6.5,6.3Hz,2H),2.34(s,6H)；13C NMR(125MHz,CDCl3)δ138.2,137.3,136.9,129.0,126.9,117.3,82.2,66.5,63.0,21.0；HRMS(ESI-APCI):Calcd.for C24H30O4(M+NH4):400.2488,Found:400.2506；HPLC conditions:Chiralcel OJ-H column,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/9,tmajor＝16.37min,tminor＝26.78min；99％ee.
Figure BDA0002266931040000213
IIIn:HPLC analysis indicated 24:1 dr；1H NMR(500MHz,CDCl3)δ7.61(dd,J＝7.8,1.8Hz,2H),7.30–26(m,2H),7.01–6.98(m,2H),6.90(dd,J＝8.2,1.2Hz,2H),6.14(dd,J＝17.6,10.9Hz,2H),5.28(dd,J＝11.0,1.4Hz,2H),5.22(dd,J＝17.6,1.4Hz,2H),4.21(d,J＝11.8Hz,2H),4.09(d,J＝11.8Hz,2H),3.77(s,6H),3.67–3.63(m,4H),2.99(bs,2H)；13C NMR(125MHz,CDCl3)δ156.8,137.9,128.9,128.8,128.5,120.6,116.0,111.7,82.2,64.7,63.0,55.2；HRMS(ESI-APCI):Calcd.for C24H30O6(M+NH4):432.2386,Found:432.2407；HPLC conditions:Chiralcel AS-H column,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/24,tmajor＝39.45min；>99％ee.
Figure BDA0002266931040000221
IIIo：HPLC analysis indicated 14:1 dr；1H NMR(500MHz,CDCl3)δ7.29(dd,J＝8.0,7.9Hz,2H),7.06(s,2H),7.00(d,J＝7.8Hz,2H),6.83(dd,J＝8.2,2.4Hz,2H),6.09(dd,J＝17.6,11.1Hz,2H),5.43(dd,J＝10.2,10.2Hz,2H),5.40(dd,J＝8.0,8.0Hz,2H),3.98(d,J＝11.8Hz,2H),3.92(d,J＝12.0Hz,2H),3.80(s,6H),3.62–3.50(m,4H),2.92(dd,J＝6.7,6.5Hz,2H)；13C NMR(125MHz,CDCl3)δ159.6,141.7,137.7,129.3,119.3,117.8,113.4,112.5,82.30,66.8,63.1,55.2；HRMS(ESI-APCI):Calcd.for C24H30O6(M+NH4):432.2386,Found:432.2406；HPLC conditions:Chiralcel OD-H column,220nm,flowrate:1ml/min,i-PrOH/hexanes＝1/9,tminor＝24.49min,tmajor＝16.98min；98％ee.
Figure BDA0002266931040000222
IIIp:HPLC analysis indicated 4:1 dr；1H NMR(500MHz,CDCl3)δ7.34(d,J＝8.8Hz,4H),6.89(d,J＝8.8Hz,4H),6.08(dd,J＝17.6,11.0Hz,2H),5.40(dd,J＝11.0,1.2Hz,2H),5.37(dd,J＝17.6,1.2Hz,2H),3.99(d,J＝11.8Hz,2H),3.90(d,J＝7.8Hz,2H),3.80(s,6H),3.55–3.43(m,4H),2.90(dd,J＝6.8,6.2Hz,2H)；13C NMR(125MHz,CDCl3)δ159.0,138.3,131.9,128.2,117.3,113.7,82.0,66.5,62.9,55.2；HRMS(ESI-APCI):Calcd.forC24H30O6(M+NH4):432.2386,Found:432.2406；HPLC conditions:Chiralcel AS-Hcolumn,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/9,tminor＝21.00min,tmajor＝26.52min；96％ee.
Figure BDA0002266931040000231
IIIq:HPLC analysis indicated 6:1 dr；1H NMR(500MHz,CDCl3)δ7.43–7.40(m,4H),7.05(dd,J＝8.6,8.4Hz,4H),6.06(dd,J＝17.6,11.0Hz,2H),5.45(dd,J＝11.0,1.9Hz,2H),5.37(dd,J＝17.6,1.2Hz,2H),3.95(d,J＝11.4Hz,2H),3.92(d,J＝11.5Hz,2H),3.59–3.48(m,4H),2.88(dd,J＝6.4,6.4Hz,2H)；13C NMR(125MHz,CDCl3)δ163.1,161.2,137.8,137.7,135.8,128.8,118.0,117.9,115.2,115.0,81.9,66.4,63.0；HRMS(ESI-APCI):Calcd.for C22H24F2O4(M+NH4):408.1986,Found:408.2004；HPLC conditions:Lux 5u Cellulose-2,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/5.7,tminor＝8.80min,tmajor＝10.76min；99％ee.
Figure BDA0002266931040000232
IIIr:HPLC analysis indicated 15:1 dr；1H NMR(500MHz,CDCl3)δ7.39–7.36(m,4H),7.35–7.32(m,4H),6.05(dd,J＝17.6,11.0Hz,2H),5.45(dd,J＝11.2,1.2Hz,2H),5.37(dd,J＝17.7,1.0Hz,2H),3.94(d,J＝12.2Hz,2H),3.91(d,J＝7.8Hz,2H),3.60–3.49(m,4H),2.86(dd,J＝6.2,6.2Hz,2H)；13C NMR(125MHz,CDCl3)δ138.6,137.5,133.6,128.5,128.4,118.2,81.9,66.4,63.0；HRMS(ESI-APCI):Calcd.for C22H24Cl2O4(M+Na):445.0949,Found:445.0942；HPLC conditions:Lux 5u Cellulose-2,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/19,tminor＝35.17min,tmajor＝43.81min；99％ee.
Figure BDA0002266931040000233
IIIs:HPLC analysis indicated 13:1 dr；1H NMR(500MHz,CDCl3)δ7.49(d,J＝8.6Hz,4H),7.31(d,J＝8.6Hz,4H),6.05(dd,J＝17.6,11.0Hz,2H),5.45(dd,J＝11.0,1.1Hz,2H),5.37(dd,J＝17.7,1.0Hz,2H),3.94(d,J＝11.5Hz,2H),3.91(d,J＝8.8Hz,2H),3.57–3.49(m,4H),2.81(dd,J＝6.4,6.2Hz,2H)；13C NMR(125MHz,CDCl3)δ139.2,137.5,131.5,128.8,121.8,118.2,82.0,66.4,63.0；HRMS(ESI-APCI):Calcd.for C22H24Br2O4(M+NH4):530.0385,Found:530.0380；HPLC conditions:Chiralcel OJ-H column,220nm,flowrate:1ml/min,i-PrOH/hexanes＝1/9,tmajor＝15.53min,tminor＝21.11min；99％ee.
Figure BDA0002266931040000241
IIIt:HPLC analysis indicated 3:1 dr；1H NMR(500MHz,CDCl3)δ6.97(d,J＝1.7Hz,2H),6.90–6.86(m,2H),6.79(d,J＝8.1Hz,2H),6.06(dd,J＝17.6,11.0Hz,2H),5.96(s,4H),5.43(dd,J＝7.9,1.2Hz,2H),5.40(dd,J＝13.4,1.6Hz,2H),3.92(d,J＝9.0Hz,2H),3.88(d,J＝12.0Hz,2H),3.57–3.3.46(m,4H),2.88(bs,4H)；13C NMR(125MHz,CDCl3)δ147.8,147.0,138.0,133.9,120.3,117.6,107.9,101.0,82.0,66.6,66.5,62.9；HRMS(ESI-APCI):Calcd.for C24H26O8(M+NH4):460.1971,Found:460.1980；HPLC conditions:Lux 5uCellulose-2,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/4,tminor＝19.20min,tmajor＝29.27min；93％ee.
Figure BDA0002266931040000242
IIIu:HPLC analysis indicated 3:1 dr；1H NMR(500MHz,CDCl3)δ7.58(s,2H),7.45–7.43(m,2H),7.30–7.26(m,2H),6.03(dd,J＝16.8,11.0Hz,2H),5.50(dd,J＝11.0,11Hz,2H),5.39(dd,J＝17.8,3.8Hz,2H),3.93(d,J＝8.6Hz,2H),3.87(d,J＝11.7Hz,2H),3.63–3.51(m,4H),2.82(bs,2H)；13C NMR(125MHz,CDCl3)δ140.7,136.8,132.6,131.8,130.3,129.2,126.5,119.0,81.7,66.5,63.1；HRMS(ESI-APCI):Calcd.for C22H22Cl4O4(M+NH4):510.0616,Found:510.0615；HPLC conditions:Chiralcel AD-H column,220nm,flowrate:1ml/min,i-PrOH/hexanes＝1/5.7,tminor＝10.40min,tmajor＝11.32min；95％ee.
Figure BDA0002266931040000251
IIIv:HPLC analysis indicated 6:1 dr；1H NMR(500MHz,CDCl3)δ7.92–7.90(m,2H),7.85–7.82(m,6H),7.57–7.55(m,2H),7.50–7.47(m,4H),6.22(dd,J＝17.6,11.0Hz,2H),5.49(dd,J＝6.5,1.2Hz,2H),5.46(dd,J＝13.0,1.2Hz,2H),4.15(d,J＝11.8Hz,2H),4.06(d,J＝11.6Hz,2H),3.65–3.56(m,4H),3.04(bs,2H)；13C NMR(125MHz,CDCl3)δ138.0,137.4,133.0,132.8,128.2,128.1,127.5,126.2,126.1,126.0,125.0,117.9,82.5,66.5,63.2；HRMS(ESI-APCI):Calcd.for C30H30O4(M+NH4):472.2488,Found:472.2499；HPLCconditions:Lux 5u Cellulose-2,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/9,tminor＝23.76min,tmajor＝39.04min；98％ee.
Figure BDA0002266931040000252
IIIw:HPLC analysis indicated 2:1 dr；1H NMR(500MHz,CDCl3)δ7.32–7.30(m,2H),7.28–7.27(m,2H),7.08(dd,J＝5.0,1.2Hz,2H),6.09(dd,J＝17.4,11.0Hz,2H),5.41(dd,J＝8.5,3.0Hz,2H),5.38(dd,J＝11.8,1.8Hz,2H),3.98(d,J＝11.6Hz,2H),3.86(d,J＝6.8Hz,2H),3.54–3.40(m,4H),2.90(dd,J＝7.6,6.7Hz,2H)；13C NMR(125MHz,CDCl3)δ141.4,137.8,126.9,125.8,122.8,117.4,80.8,66.7,63.2；HRMS(ESI-APCI):Calcd.forC18H22O4S2(M+NH4):384.1303,Found:384.1319；HPLC conditions:Lux 5u Cellulose-2,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/4,tminor＝9.55min,tmajor＝17.62min；93％ee.
Figure BDA0002266931040000253
IIIx:HPLC analysis indicated 2:1 dr；1H NMR(400MHz,CDCl3)δ7.34-7.29(m,2H),7.25-7.23(m,2H),5.92(dd,J＝17.5,11.1Hz,2H),5.35(dd,J＝5.1,1.2 2H),5.32(dd,J＝11.6,1.4Hz,2H),4.41(s,4H),3.57(d,J＝11.0,Hz,2H),3.50(d,J＝11.0Hz,2H),2.13(dd,J＝6.7,6.4Hz,2H),1.39(s,6H)；13C NMR(126MHz,CDCl3)δ139.7,139.2,128.4,126.6,126.5,117.2,78.5,69.5,64.8,18.6；HRMS(ESI-MS):Calcd.for C18H26O4(M+Na):329.1729,Found:329.1725；HPLC conditions:Lux 5u Cellulose-2,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/9,tmajor＝12.67min,tminor＝15.33min；84％ee.
Figure BDA0002266931040000261
IXb:HPLC analysis indicated 9:1dr；1H NMR(500MHz,CDCl3)δ7.65(t,J＝7.6Hz,1H),7.47(d,J＝8.6Hz,4H),7.34(d,J＝8.6Hz,4H),7.14(d,J＝7.7Hz,2H),6.28(bs,2H),6.14(dd,J＝17.7,11.0Hz,2H),5.43(dd,J＝11.0,1.2Hz,2H),5.34(dd,J＝17.7,1.1Hz,2H),4.63(d,J＝13.7Hz,2H),4.48(d,J＝13.7Hz,2H),4.04-3.92(m,4H)；13C NMR(125MHz,CDCl3)δ158.1,139.7,137.7,137.6,131.3,128.9,121.5,120.6,118.3,83.5,66.5,65.9；HRMS(ESI-MS):Calcd.for C27H27Br2NO4(M+H):588.0385,Found:588.0379；HPLCconditions:Lux 5u Cellulose-2,220nm,flow rate:1ml/min,i-PrOH/hexanes＝1/9,tminor＝33.24min,tmajor＝53.50min；97％ee.
Figure BDA0002266931040000262
IXc:HPLC analysis indicated 7:1dr；1H NMR(500MHz,CDCl3)δ7.92(s,2H),7.85-7.80(m,6H),7.64(t,J＝7.7Hz,1H),7.60(dd,J＝8.6,2.0Hz,2H),7.49-7.45(m,4H),7.14(d,J＝7.7Hz,2H),6.29(dd,J＝17.6,11.0Hz,2H),6.23(bs,2H),5.45(dd,J＝11.0,1.4Hz,2H),5.40(d,J＝17.6,1.4Hz,2H),4.65(d,J＝13.8Hz,2H),4.55(d,J＝13.8Hz,2H),4.22(d,J＝12.1Hz,2H),4.11(d,J＝12.2Hz,2H)；13C NMR(125MHz,CDCl3)δ158.4,138.2,138.0,137.6,133.0,132.7,128.2,128.0,127.5,126.1,126.0,126.0,125.3,120.5,117.9,84.0,66.7,66.1；HRMS(ESI-MS):Calcd.for C35H33NO4(M+H):532.248,Found:532.2496；HPLC conditions:Lux 5u Cellulose-2,220nm,flow rate:1ml/min,i-PrOH/hexanes＝2/8,tmajor＝18.97min,tminor＝28.59min；99％ee.
实施例6
本实施例提供一种手性冠醚类化合物V，该化合物V其结构式如下：
Figure BDA0002266931040000271
其中：R为氢、C1-C20的烷基、C3-C16的环烷基、C4-C16的含N、O或S的杂环基、C6-C24的芳基、取代基含N、O、S、P或卤素的C6-C24的取代芳基、C6-C26的芳基烷基、-CnH2n-OR1、-CnH2n-SR2或-CnH2n-NR3R4中的一种；其中，n为1～10中任一整数，R1、R2、R3和R4为氢、C1-C8烷基、C4-C15芳基或C5-C15芳基烷基。
上述实施例中手性冠醚类化合物V，可以采用以下方法制备：
化合物IX溶解在无水四氢呋喃溶剂中，将叔丁醇钾在0℃下缓慢少量多次加到反应液中，随后室温下搅拌半个小时，再滴加吡啶-2,6-二基双(亚甲基)双(4-甲基苯磺酸盐的四氢呋喃溶液在室温下反应，反应毕，饱和氯化铵淬灭，乙酸乙酯萃取，过滤、干燥，蒸干溶剂。柱层析提纯得到化合物V,此外手性冠醚类化合物VI是手性冠醚类化合物V的对映异构体，在其合成方法中采用构型相反的手性二醇化合物X作为反应物，其他条件与化合物V的实施例一致。
以下是R为不同选择时对应的手性冠醚类化合物V1H NMR、13C NMR谱图数据，手性冠醚类化合物V可以采用上述方法制备，相应的产率和对映选择性有一定的差异。
Figure BDA0002266931040000272
Va:1H NMR(500MHz,CDCl3)δ7.65(t,J＝7.8Hz,1H),7.57(t,J＝7.6Hz,1H),7.55-7.52(m,4H),7.42(d,J＝7.7Hz,2H),7.38-7.34(m,4H),7.29-7.26(m,2H),7.16(d,J＝7.6Hz,2H),6.11(dd,J＝17.6,10.9Hz,2H),5.40(dd,J＝17.6,1.4Hz,2H),5.36(dd,J＝11.0,1.4Hz,2H),4.51(d,J＝13.2Hz,2H),4.45-4.38(m,4H),4.34(d,J＝13.9Hz,2H),4.04-3.92(m,4H)；13C NMR(125MHz,CDCl3)δ158.9,157.7,141.2,139.5,136.7,136.6,128.0,127.3,127.0,120.6,118.6,116.5,82.2,73.9,73.4,66.9；HRMS(ESI-MS):Calcd.for C34H34N2O4(M+H):535.2597,Found:535.2605.
Figure BDA0002266931040000281
Vb:1H NMR(500MHz,CDCl3)δ7.65(t,J＝7.7Hz,1H),7.59(t,J＝7.7Hz,1H),7.49(d,J＝8.6Hz,4H),7.43(d,J＝8.6Hz,4H),7.37(d,J＝7.7Hz,2H),7.12(d,J＝7.6Hz,2H),6.04(dd,J＝17.1,11.5Hz,2H),5.40(d,J＝10.1Hz,2H),5.34(dd,J＝7.0,1.2Hz,2H),4.54(d,J＝13.1Hz,2H),4.44(d,J＝13.8Hz,2H),4.37-4.30(m,4H),3.98-3.93(m,4H)；13C NMR(125MHz,CDCl3)δ158.6,157.6,140.5,139.0,136.8,136.8,131.2,129.0,121.4,120.7,118.8,117.0,81.9,73.9,73.0,66.9；HRMS(ESI-MS):Calcd.for C34H32Br2N2O4(M+H):691.0807,Found:691.0816.
Figure BDA0002266931040000282
Vc:1H NMR(500MHz,CDCl3)δ7.99(s,2H),7.86-7.80(m,6H),7.69-7.64(m,3H),7.54(t,J＝7.6Hz,1H),7.49-7.45(m,6H),7.15(d,J＝7.7Hz,2H),6.18(dd,J＝17.6,10.8Hz,2H),5.69(dd,J＝17.6,1.3Hz,2H),5.40(dd,J＝11.0,1.3Hz,2H),4.58(d,J＝13.2Hz,2H),4.51-4.44(m,4H),4.39(d,J＝13.8Hz,2H),4.16-4.07(m,4H)；13C NMR(125MHz,CDCl3)δ158.8,157.7,139.4,138.7,136.8,133.0,132.7,128.2,127.7,127.5,126.0,125.9,125.8,125.3,120.7,118.8,116.8,114.0,82.4,74.0,73.5,67.0；HRMS(ESI-MS):Calcd.for C42H38N2O4(M+H):635.2910,Found:635.2913.
以上对本发明的具体实施例进行了描述。需要理解的是，本发明并不局限于上述特定实施方式，本领域技术人员可以在权利要求的范围内做出各种变形或修改，这并不影响本发明的实质内容。

Claims (9)

1.一种手性二醇类化合物I、II、III或IV，其特征在于：所述化合物I、II、III或IV的结构式如下所示：
Figure FDA0002266931030000011
其中：R为氢、C1-C20的烷基、C3-C16的环烷基、C4-C16的含N、O或S的杂环基、C6-C24的芳基、取代基含N、O、S、P或卤素的C6-C24的取代芳基、C6-C26的芳基烷基、-CnH2n-OR1、-CnH2n-SR2或-CnH2n-NR3R4中的一种；其中，n为1～10中任一整数，R1、R2、R3和R4为氢、C1-C8烷基、C4-C15芳基或C5-C15芳基烷基；
R’为-CH2 CH2-(X-CH2CH2)m-或-CH2-Y-CH2-；其中，X为O、S或N-R5；R5为上述R1中的一种；m为0-10000中的任一整数；Y为C1-C20的烷基、C3-C16的环烷基、C4-C16的含N、O或S的杂环基、C6-C24的芳基、取代基含N、O、S、P或卤素的C6-C24的取代芳基、C6-C26的芳基烷基、-CnH2n-OR1、-CnH2n-SR2或-CnH2n-NR3R4中的一种。
2.一种权利要求1所述的一种手性二醇类化合物I、II、III或IV的制备方法，其特征在于，在有机溶剂中，以钯源与手性配体配位作用生成的钯配合物和硼化合物为催化剂，消旋4-取代-4-乙烯基-1，3-二氧戊环-2-酮类化合物VII和二醇VIII，在0-60℃下反应，得到所述化合物I、II、III或IV；
所述消旋4-取代-4-乙烯基-1，3-二氧戊环-2-酮类化合物VII和所述二醇VIII结构式如下所示：
Figure FDA0002266931030000012
其中：R为氢、C1-C20的烷基、C3-C16的环烷基、C4-C16的含N、O或S的杂环基、C6-C24的芳基、取代基含N、O、S、P或卤素的C6-C24的取代芳基、C6-C26的芳基烷基、-CnH2n-OR1、-CnH2n-SR2或-CnH2n-NR3R4中的一种；其中，n为1～10中任一整数，R1、R2、R3和R4为氢、C1-C8烷基、C4-C15芳基或C5-C15芳基烷基；
R’为-CH2 CH2-(X-CH2CH2)m-或-CH2-Y-CH2-；其中，X为O、S或N-R5；R5为上述R1中的一种；m为0-10000中的任一整数；Y为C1-C20的烷基、C3-C16的环烷基、C4-C16的含N、O或S的杂环基、C6-C24的芳基、取代基含N、O、S、P或卤素的C6-C24的取代芳基、C6-C26的芳基烷基、-CnH2n-OR1、-CnH2n-SR2或-CnH2n-NR3R4中的一种。
3.根据权利要求2所述的一种手性二醇类化合物I、II、III或IV的制备方法，其特征在于，所述有机溶剂为四氢呋喃、二氧六环、二氯甲烷、三氯甲烷、乙酸乙酯、甲苯、苯、乙醚、甲基叔丁基醚、丙酮、二甲基甲酰胺或乙腈中的一种。
4.根据权利要求2所述的一种手性二醇类化合物I、II、III或IV的制备方法，其特征在于，所述钯源为Pd2(dba)3、Pd2(dba)3·CHCl3、Pd(dba)2、[Pd(allyl)Cl]2、Pd(OAc)2、Pd(CF3COO)2、Pd(CH3CN)2Cl2或Pd(PhCN)2Cl2中的一种。
5.根据权利要求2所述的一种手性二醇类化合物I、II、III或IV的制备方法，其特征在于，所述手性配体为具有如下结构式的手性膦配体中的一种：
Figure FDA0002266931030000021
其中，A为C1-C10的烷基、C6-C16的芳基或C6-C16的取代芳基、OR1”或NR2”R3”，其中R1”为C1-C10的烷基、C6-C16的芳基或C6-C16的取代芳基，R2”、R3”分别为氢、C1-C20的烷基、C6-C20的芳基或C6-C20的取代芳基。
6.根据权利要求2所述的一种手性二醇类化合物I、II、III或IV的制备方法，其特征在于，所述硼化合物的结构式为：
Figure FDA0002266931030000022
其中：R1’、R2’、R3’为C1-C10的烷基、C6-C16的芳基或C6-C16的取代芳基、OR4’中的一种；R4’为氢、C1-C10的烷基、C6-C16的芳基或C6-C16的取代芳基中的一种。
7.根据权利要求2所述的一种手性二醇类化合物I、II、III或IV的制备方法，其特征在于，所述消旋4-取代-4-乙烯基-1，3-二氧戊环-2-酮类化合物VII、所述二醇VIII、所述钯源、所述手性配体及所述硼化合物的摩尔比为1:1-20:0.0001-0.05:0.0001-0.20:0.0001-0.40。
8.一种手性冠醚类化合物V或VI，其特征在于：所述化合物V或VI的结构式如下所示：
Figure FDA0002266931030000031
其中：R为氢、C1-C20的烷基、C3-C16的环烷基、C4-C16的含N、O或S的杂环基、C6-C24的芳基、取代基含N、O、S、P或卤素的C6-C24的取代芳基、C6-C26的芳基烷基、-CnH2n-OR1、-CnH2n-SR2或-CnH2n-NR3R4中的一种；其中，n为1～10中任一整数，R1、R2、R3和R4为氢、C1-C8烷基、C4-C15芳基或C5-C15芳基烷基。
9.一种权利要求8所述的手性冠醚类化合物V或VI的制备方法，其特征在于，包括：以化合物IX或X为原料，将所述原料与化合物XI，在叔丁醇钾存在下，在四氢呋喃中反应，得到所述化合物V或VI；
其中：所述化合物IX、X和XI的结构式如下：
Figure FDA0002266931030000032
其中：R为氢、C1-C20的烷基、C3-C16的环烷基、C4-C16的含N、O或S的杂环基、C6-C24的芳基、取代基含N、O、S、P或卤素的C6-C24的取代芳基、C6-C26的芳基烷基、-CnH2n-OR1、-CnH2n-SR2或-CnH2n-NR3R4中的一种；其中，n为1～10中任一整数，R1、R2、R3和R4为氢、C1-C8烷基、C4-C15芳基或C5-C15芳基烷基；
B为Cl、Br、I、-OSO2Me或-OSO2C6H4CH3中的一种。
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