CN113735894A - 一类同时含有轴手性和中心手性的2,3-联烯醇类化合物及其制备方法和应用 - Google Patents

一类同时含有轴手性和中心手性的2,3-联烯醇类化合物及其制备方法和应用 Download PDF

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CN113735894A
CN113735894A CN202111159666.8A CN202111159666A CN113735894A CN 113735894 A CN113735894 A CN 113735894A CN 202111159666 A CN202111159666 A CN 202111159666A CN 113735894 A CN113735894 A CN 113735894A
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张丰华
王兆彬
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Abstract

本发明涉及一类同时含有轴手性和中心手性的2,3‑联烯醇类化合物及其制备方法和应用。该2,3‑联烯醇类化合物是具有式I的化合物或所述化合物的对映体、消旋体，其主要结构特征是分子中同时含有轴手性和中心手性。该化合物是由铬催化炔丙基卤化物与醛类化合物不对称加成所合成的。该2,3‑联烯醇类化合物在有机合成中有着广泛的应用和转化，有着重大的实用价值。此外本发明提供的手性2,3‑联烯醇的制备方法具有：反应原料廉价易得、反应操作简便、反应底物适用范围广、反应容易放大、反应条件温和等优点，具有实用价值。

Description

一类同时含有轴手性和中心手性的2,3-联烯醇类化合物及其 制备方法和应用
技术领域
本发明属于有机合成技术领域，涉及一类同时含有轴手性和中心手性的2,3-联烯醇类化合物及其制备方法和应用。
背景技术
2,3-联烯醇是一类同时含有联烯(1,2-二烯)和羟基的一类化合物。由于其结构中同时含有两个活性基团，因而赋予其很高的反应活性，可以发生过渡金属催化的自身异构环化反应、钯催化偶联反应、钌催化环羰基化反应、扩环反应、亲电试剂参与的环化反应、分子内环加成反应、自由基反应、零价钯催化下基于亚甲基-π-烯丙基钯中间体生成联烯或1,3-共轭二烯的反应，以及重排反应等，因此其在有机合成中占据着重要的地位。例如，2,3-联烯醇不仅仅是合成一些天然产物的重要中间体，如(+)-Varitriol，Boivinianin B，Amphidinolide X，(+)-Furanomycin等；也是一些重要有机化合物的合成前体，如2,5-二氢呋喃化合物、烯基环氧化合物、2(5H)-呋喃酮类化合物、α,β-不饱和酮等。
手性2,3-联烯醇目前主要的合成方法有以下三种：一是酶催化外消旋2,3-联烯醇的动力学拆分，由于酶通常对底物具有较强的专一性，因此该方法中底物结构相对单一，并且该方法仅能用于具有单个中心手性的2,3-联烯醇的合成，使得该方法的普适性和应用性较低。二是使用手性原料合成手性的2,3-联烯醇，因为使用的手性原料需要复杂的制备和纯化，因此适用的底物也具有较大的局限性，该方法的实用性较差。三是使用手性催化剂催化不对称合成。该方法使用催化量的手性催化剂可以将各类底物转化成手性2,3-联烯醇，反应具有较好的普适性和较高的效率。在该类方法中，绝大多数方法只能用于制备具有单个中心手性的2,3-联烯醇，如Yamamoto课题组(DOI:10.1021/ja0679578)、Reddy课题组(DOI:10.1039/c2cc34371a)、Ohmiya课题组(DOI:10.1039/d0cc02619k)等报道的。同时含有轴手性和中心手性的2,3-联烯醇类化合物及其制备方法目前报道方法较少。2016年，List课题组使用炔基取代的乙烯酮缩醛和芳基醛作为底物，双磺酰亚胺作为催化剂，实现了一类手性2,3-联烯醇的合成(DOI:10.1002/anie.201603649)。在2016和2018年，Feng课题组使用靛红作为底物，分别使用手性金和铜催化剂，实现了含靛红结构的手性2,3-联烯醇的合成(DOI：10.1021/acscatal.6b00294和DOI:10.1016/j.chempr.2018.04.012)。2020年，Yin课题组报道了铜催化炔丙基酯对醛的加成反应，也实现了手性2,3-联烯醇的合成(DOI:10.1002/anie.201912140)。但是上述方法均使用一些特殊的活化的底物，因此其产物结构具有较大的局限性，如联烯片段中都必须是含有酯基官能团。这些方法对于本发明专利中合成的手性2,3-联烯醇在联烯片段中为简单烷基取代的产物是没法得到的。
Figure BDA0003289599520000021
发展一类普适的合成方法，从简单的原料出发，制备出一类同时含有轴手性和中心手性的2,3-联烯醇类化合物的关键是在于寻找合适的手性金属催化剂。
发明内容
本发明的目的在于提供一类同时含有轴手性和中心手性的2,3-联烯醇类化合物的制备方法。本发明提供的同时含有轴手性和中心手性的2,3-联烯醇类化合物，是具有式I的化合物或所述化合物的对映体、消旋体。
Figure BDA0003289599520000022
其中，R1选自C1～C10的烃基、苯基、取代苯基、1-萘基、2-萘基、杂芳基或苄基，所述的苯基上的取代基为C1～C10的烃基、烷氧基、三氟甲基、卤素、硼酸基、巯基、氰基、酯基、磺酰基，取代基数量为1～5，杂芳基为呋喃基、噻吩基、苯丙噻吩基、吲哚基或吡啶基；
R2选自三烷基取代硅基、三芳基取代硅基、二烷基取代硅基、C1～C10的烃基、苯基、取代苯基、1-萘基、2-萘基、杂芳基或苄基，所述的苯基上的取代基为C1～C10的烃基、烷氧基、三氟甲基、卤素、硼酸基、巯基、氰基、酯基、磺酰基，取代基数量为1～5，杂芳基为呋喃基、噻吩基、苯丙噻吩基、吲哚基或吡啶基；
R3选自C1～C10的烃基。
本发明提供的同时含有轴手性和中心手性的2,3-联烯醇类化合物的制备方法，是以醛和炔丙基卤化物为起始原料经过下述反应式制备：
Figure BDA0003289599520000023
其中，炔丙基卤化物1、醛2、式I中R1～R3的含义与上述一致，X选自溴和氯。炔丙基卤化物1所示的化合物和醛2所示的化合物是按文献方法制备的。同时含有轴手性和中心手性的2,3-联烯醇类化合物的制备方法包括以下步骤：
在有机溶剂中，使用预先制备好的手性铬催化剂，与炔丙基卤化物1、醛2在还原剂和解离剂存在下发生反应得到式I所示的化合物。
在上述合成方法中，手性铬催化剂的制备方法为：由二氯化铬与选自手性配体La-Lk中任意一种在有机溶剂中室温下反应两个小时以上得到的。
Figure BDA0003289599520000031
作为优选方案，上述合成方法的具体操作是：在手套箱中，二氯化铬与上述的手性配体La-Lk在有机溶剂中室温下反应2小时，得到手性铬催化剂。随后将炔丙基卤化物1、醛2、还原试剂、解离剂依次按顺序加入含有手性铬催化剂中，室温下反应12小时，经柱层析分离即可得到手性2,3-联烯醇。
在上述合成方法中，所述的有机溶剂可为乙二醇二甲醚、四氢呋喃、乙腈、甲苯、二甲苯、甲基叔丁基醚、乙醚、二氧六环、N,N-二甲基甲酰胺、二甲亚砜、二氯甲烷、氯仿、1,2-二氯乙烷中的一种或其中几种的混合溶剂；所述的还原试剂可为锰粉、锌粉、氢化铝锂、硼氢化钠、三乙酰氧基硼氢化钠、腈基硼氢化钠、三氯硅烷，苯硅烷中的一种；所述的解离剂可为三甲基氯硅烷、三乙基氯硅烷、三苯基氯硅烷、二氯二茂锆中的一种。
与现有技术相比，本发明具有如下效果：
1)本发明提供的手性2,3-联烯醇同时含有轴手性和中心手性，该类产物在有机合成中有着广泛的应用和转化，具有重大的实用价值。
2)本发明提供的手性2,3-联烯醇的制备方法具有：反应原料廉价易得、反应操作简便、反应底物适用范围广、反应容易放大、反应条件温和等优点，能够实现工业化生产和应用。。
3)本发明提供的手性2,3-联烯醇通过亲电环化反应合成了多手性中心的四氢呋喃类化合物和天然产物(+)-varitriol。
具体实施方式
下面结合实施例对本发明作进一步详细、完整的说明，列出的实施将有助于理解本发明，但不能限制本发明的内容。
实施例1：配体La对反应的影响
Figure BDA0003289599520000041
在手套箱中，二氯化铬与手性配体La在有机溶剂DME(乙二醇二甲醚)中室温下反应2小时，得到手性铬催化剂。随后将炔丙基卤化物1(0.6mmol)、苯甲醛2(0.4mmol)、锰粉(还原试剂)、二氯二茂锆(解离剂)依次按顺序加入含有手性铬催化剂中，室温下反应12小时。反应结束后，加入200uL水淬灭反应，旋转蒸发仪脱除溶剂后得粗产物。经短硅胶柱过滤除去催化剂、锰粉之后，用薄层层析或者核磁共振分析反应的转化率、收率、dr值，高效液相色谱分析产物的光学纯度，所得实验结果：收率为86％，dr为>20:1，ee值为92。
实施例2：配体Lc对反应的影响
Figure BDA0003289599520000042
在手套箱中，二氯化铬与手性配体Lc在有机溶剂DME(乙二醇二甲醚)中室温下反应2小时，得到手性铬催化剂。随后将炔丙基卤化物1(0.6mmol)、苯甲醛2(0.4mmol)、锰粉(还原试剂)、二氯二茂锆(解离剂)依次按顺序加入含有手性铬催化剂中，室温下反应12小时。反应结束后，加入200uL水淬灭反应，旋转蒸发仪脱除溶剂后得粗产物。经短硅胶柱过滤除去催化剂、锰粉之后，用薄层层析或者核磁共振分析反应的转化率、收率、dr值，高效液相色谱分析产物的光学纯度，所得实验结果：收率为82％，dr为10:1，ee值为72。
实施例3：配体Le对反应的影响
Figure BDA0003289599520000043
在手套箱中，二氯化铬与手性配体Le在有机溶剂DME(乙二醇二甲醚)中室温下反应2小时，得到手性铬催化剂。随后将炔丙基卤化物1(0.6mmol)、苯甲醛2(0.4mmol)、锰粉(还原试剂)、二氯二茂锆(解离剂)依次按顺序加入含有手性铬催化剂中，室温下反应12小时。反应结束后，加入200uL水淬灭反应，旋转蒸发仪脱除溶剂后得粗产物。经短硅胶柱过滤除去催化剂、锰粉之后，用薄层层析或者核磁共振分析反应的转化率、收率、dr值，高效液相色谱分析产物的光学纯度，所得实验结果：收率为92％，dr为4:1，ee值为55。
实施例4：配体Lh对反应的影响
Figure BDA0003289599520000051
在手套箱中，二氯化铬与手性配体Lh在有机溶剂DME(乙二醇二甲醚)中室温下反应2小时，得到手性铬催化剂。随后将炔丙基卤化物1(0.6mmol)、苯甲醛2(0.4mmol)、锰粉(还原试剂)、二氯二茂锆(解离剂)依次按顺序加入含有手性铬催化剂中，室温下反应12小时。反应结束后，加入200uL水淬灭反应，旋转蒸发仪脱除溶剂后得粗产物。经短硅胶柱过滤除去催化剂、锰粉之后，用薄层层析或者核磁共振分析反应的转化率、收率、dr值，高效液相色谱分析产物的光学纯度，所得实验结果：收率为90％，dr为4:1，ee值为77。
实施例5：配体Ld对反应的影响
Figure BDA0003289599520000052
在手套箱中，二氯化铬与手性配体Ld在有机溶剂DME(乙二醇二甲醚)中室温下反应2小时，得到手性铬催化剂。随后将炔丙基卤化物1(0.6mmol)、苯甲醛2(0.4mmol)、锰粉(还原试剂)、二氯二茂锆(解离剂)依次按顺序加入含有手性铬催化剂中，室温下反应12小时。反应结束后，加入200uL水淬灭反应，旋转蒸发仪脱除溶剂后得粗产物。经短硅胶柱过滤除去催化剂、锰粉之后，用薄层层析或者核磁共振分析反应的转化率、收率、dr值，高效液相色谱分析产物的光学纯度，所得实验结果：收率为88％，dr为>20:1，ee值为98。该2,3-联烯醇I1的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALPAK IG-3 column(5％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:1.8min(major),2.1min(minor).
1H NMR(500MHz,CDCl3):δ7.39–7.35(m,2H),7.31(t,J＝7.5Hz,2H),7.25–7.22(m,1H),5.14(brs,1H),5.10(td,J＝6.8,2.1Hz,1H),2.33(s,1H),2.01(p,J＝7.4Hz,2H),1.17–1.11(m,3H),1.07 1.08–1.06(m,9H),0.97–0.90(m,12H).
13C NMR(126MHz,CDCl3)δ206.3,143.6,128.1,127.5,127.1,99.2,91.9,72.6,22.0,18.6,18.5,14.1,11.7.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C21H33Si:313.2351,found:313.2356.
[α]24 D＝+105.6(c＝0.5,CHCl3).
实施例6：手性2,3-联烯醇的合成
Figure BDA0003289599520000061
在手套箱中，二氯化铬与手性配体Ld在有机溶剂DME(乙二醇二甲醚)中室温下反应2小时，得到手性铬催化剂。随后将炔丙基卤化物1(0.6mmol)、醛2(0.4mmol)、锰粉(还原试剂)、二氯二茂锆(解离剂)依次按顺序加入含有手性铬催化剂中，室温下反应12小时。反应结束后，加入200uL水淬灭反应，旋转蒸发仪脱除溶剂后得粗产物。经短硅胶柱过滤除去催化剂、锰粉之后，用薄层层析或者核磁共振分析反应的转化率、收率、dr值，高效液相色谱分析产物的光学纯度，所得实验结果见表1。
表1 2,3-联烯醇的不对称催化合成
Figure BDA0003289599520000062
Figure BDA0003289599520000071
Figure BDA0003289599520000081
2,3-联烯醇I2的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALCEL OD-3 column(3％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:1.2min(major),1.6min(minor).
1H NMR(600MHz,CDCl3)δ7.36–7.32(m,2H),7.02–6.98(m,2H),5.13(brs,1H),5.11(td,J＝6.8,2.1Hz,1H),2.32(s,1H),2.01(qd,J＝7.5,0.7Hz,2H),1.17–1.09(m,3H),1.08–1.06(m,9H),0.98–0.92(m,12H).
13C NMR(151MHz,CDCl3)δ206.3(s),162.2(d,J＝245.4Hz),139.5(d,J＝3.1Hz),128.7(d,J＝8.1Hz),114.9(d,J＝21.4Hz),99.3(s),92.0(s),72.0(s),21.9(s),18.6(s),18.5(s),14.1(s),11.7(s).
19F NMR(471MHz,CDCl3)δ-115.17.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C21H32SiF:331.2257,found:331.2238.
[α]24 D＝+161.2(c＝0.5,CHCl3)
2,3-联烯醇I3的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALCEL OD-3 column(5％MeOHin CO2,1.5mL/min)；retention times for compound obtained using(R,S)-Ld:1.5min(major),2.1min(minor).
1H NMR(600MHz,CDCl3)δ7.32–7.27(m,4H),5.12(brs,1H),5.09(td,J＝6.9,2.0Hz,1H),2.30(s,1H),1.98(p,J＝7.4Hz,2H),1.18–1.10(m,3H),1.07(d,J＝7.3Hz,9H),0.97(d,J＝7.3Hz,9H),0.92(t,J＝7.5Hz,3H).
13C NMR(151MHz,CDCl3)δ206.7,142.3,133.1,128.4,128.2,99.1,91.9,72.0,21.9,18.6,18.5,14.1,11.7.
HRMS(APCI)m/z[M–C3H7]+ calcd for C18H26ClOSi:321.1441,found:321.1431.
[α]24 D＝+142.4(c＝0.5,CHCl3)
2,3-联烯醇I4的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALCEL OD-3 column(5％MeOHin CO2,1.5mL/min)；retention times for compound obtained using(R,S)-Ld:1.9min(major),2.5min(minor).
1H NMR(600MHz,CDCl3)δ7.45–7.42(m,2H),7.25–7.22(m,2H),5.10(brs,1H),5.07(td,J＝6.9,2.0Hz,1H),2.29(s,1H),1.97(p,J＝7.4Hz,2H),1.18–1.10(m,3H),1.07(d,J＝7.3Hz,9H),0.97(d,J＝7.4Hz,9H),0.91(t,J＝7.5Hz,3H).
13C NMR(151MHz,CDCl3)δ206.8,142.8,131.1,128.7,121.2,99.1,91.9,72.1,21.9,18.7,18.6,14.1,11.7.
HRMS(APCI)m/z[M–C3H7]+ calcd for C18H26BrOSi:365.0936,found:365.0902.
[α]24 D＝+144.0(c＝0.5,CHCl3)
2,3-联烯醇I5的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALPAK IC-3 column(5％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:3.5min(major),2.9min(minor).
1H NMR(500MHz,CDCl3)δ7.32–7.27(m,2H),6.88–6.82(m,2H),5.13(td,J＝6.9,2.2Hz,1H),5.09(brs,1H),3.79(s,3H),2.34(s,1H),2.11–1.99(m,2H),1.12(dt,J＝9.7,7.1Hz,3H),1.07(d,J＝7.1Hz,9H),0.99(t,J＝7.5Hz,3H),0.94(d,J＝7.2Hz,9H).
13C NMR(126MHz,CDCl3)δ205.78,159.0,135.8,128.4,113.5,99.3,91.9,72.0,55.2,22.1,18.6,18.4,14.2,11.6.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C22H35SiO:343.2457,found:343.2460.
[α]24 D＝+146.4(c＝0.5,CHCl3)
2,3-联烯醇I6的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALCEL OJ-3 column(5％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:1.7min(major),1.3min(minor).
1H NMR(500MHz,CDCl3)δ7.31–7.28(m,2H),7.23–7.19(m,2H),5.12–5.09(m,2H),2.46(s,3H),2.32(s,1H),2.01(p,J＝7.3Hz,2H),1.17–1.10(m,3H),1.07(d,J＝7.2Hz,9H),0.98–0.92(m,12H).
13C NMR(126MHz,CDCl3)δ206.3,140.7,137.4,127.6,126.5,99.1,91.8,72.2,22.0,18.6,18.5,16.1,14.1,11.6.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C22H35SiS:359.2229,found:359.2263.
[α]24 D＝+171.2(c＝0.5,CHCl3)
2,3-联烯醇I7的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALPAK IG-3 column(5％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:3.1min(major),2.7min(minor).
1H NMR(500MHz,CDCl3)δ7.75(d,J＝7.9Hz,2H),7.38(d,J＝7.9Hz,2H),5.14(s,1H),5.09(td,J＝6.8,1.9Hz,1H),2.28(s,1H),1.99(p,J＝7.4Hz,2H),1.34(s,12H),1.17–1.10(m,3H),1.07(d,J＝7.2Hz,9H),0.99–0.90(m,12H).
13C NMR(126MHz,CDCl3)δ206.6,146.8,134.6,126.4,99.0,91.8,83.7,72.6,24.9(two carbons),21.9,18.7,18.5,14.1,11.7.
HRMS(APCI)m/z[M–C3H7]+ calcd for C24H38BO3Si:413.2688,found:413.2688.
[α]24 D＝+134.4(c＝0.5,CHCl3)
2,3-联烯醇I8的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALPAK IB N-3 column(10％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:2.2min(major),2.9min(minor).
1H NMR(500MHz,CDCl3)δ7.89(d,J＝8.4Hz,2H),7.57(d,J＝8.3Hz,2H),5.26(d,J＝4.0Hz,1H),5.04(td,J＝6.9,1.8Hz,1H),3.02(s,3H),2.37(d,J＝5.6Hz,1H),1.94–1.85(m,2H),1.22–1.13(m,3H),1.09(d,J＝7.3Hz,9H),1.01(d,J＝7.3Hz,9H),0.82(t,J＝7.5Hz,3H).
13C NMR(126MHz,CDCl3)δ207.8,150.3,139.2,127.7,127.1,98.9,91.8,72.2,44.6,21.6,18.6,18.6,14.0,11.7.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C22H35SiO2S:391.2127,found:391.2124.
[α]24 D＝+90.0(c＝0.5,CHCl3)
2,3-联烯醇I9的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALCEL OD-3 column(5％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:0.8min(major),1.3min(minor).
1H NMR(500MHz,CDCl3)δ7.57(d,J＝8.2Hz,2H),7.48(d,J＝8.2Hz,2H),5.21(d,J＝3.6Hz,1H),5.04(td,J＝6.9,1.8Hz,1H),2.32(d,J＝5.5Hz,1H),1.96–1.89(m,2H),1.21–1.13(m,3H),1.08(d,J＝7.3Hz,9H),0.99(d,J＝7.3Hz,9H),0.84(t,J＝7.5Hz,3H).
13C NMR(126MHz,CDCl3)δ207.4(s),147.8(q,J＝1.1Hz),129.6(q,J＝32.3Hz),127.1(s),124.9(q,J＝3.8Hz),124.2(q,J＝271.9Hz),99.0(s),91.8(s),72.3(s),21.7(s),18.6(s),18.5(s),13.9(s),11.7(s).
19F NMR(471MHz,CDCl3)δ-62.44.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C22H32SiF3:381.2225,found:381.2269.
[α]24 D＝+114.4(c＝0.5,CHCl3)
2,3-联烯醇I10的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALPAK AD-3 column(5％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:2.2min(major),2.7min(minor).
1H NMR(500MHz,CDCl3)δ7.97(d,J＝8.3Hz,2H),7.42(d,J＝8.3Hz,2H),5.19(s,1H),5.03(td,J＝6.8,1.9Hz,1H),3.89(s,3H),2.45(s,1H),1.92(p,J＝7.4Hz,2H),1.19–1.11(m,3H),1.06(d,J＝7.3Hz,9H),0.97(d,J＝7.4Hz,9H),0.85(t,J＝7.5Hz,3H).
13C NMR(126MHz,CDCl3)δ207.2,167.0,149.0,129.3,129.0,126.8,98.9,91.7,72.3,52.0,21.7,18.6,18.5,14.0,11.6.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C23H35SiO2:371.2406,found:371.2393.
[α]24 D＝+129.6(c＝0.5,CHCl3)
2,3-联烯醇I11的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALCEL OD-3 column(5％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:1.9min(major),2.9min(minor).
1H NMR(500MHz,CDCl3)δ7.61(d,J＝8.3Hz,2H),7.47(d,J＝8.2Hz,2H),5.22(d,J＝1.1Hz,1H),5.02(td,J＝6.9,1.8Hz,1H),2.33(brs,1H),1.90(p,J＝7.4Hz,2H),1.21–1.13(m,3H),1.08(d,J＝7.3Hz,9H),1.01(d,J＝7.3Hz,9H),0.83(t,J＝7.5Hz,3H).
13C NMR(126MHz,CDCl3)δ207.9,149.4,131.9,127.5,119.0,111.0,98.8,91.8,72.3,21.6,18.6,18.6,14.0,11.7.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C22H32SiN:338.2304,found:338.2310.
[α]24 D＝+100.0(c＝0.5,CHCl3)
2,3-联烯醇I12的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALPAK IG-3 column(5％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:5.8min(major),6.5min(minor).
1H NMR(600MHz,CDCl3)δ7.84–7.79(m,4H),7.54(dd,J＝8.6,1.5Hz,1H),7.49–7.44(m,2H),5.32(s,1H),5.13(td,J＝6.9,2.1Hz,1H),2.41(brs,1H),2.03(p,J＝7.3Hz,2H),1.22–1.14(m,3H),1.10(d,J＝7.4Hz,9H),0.97(d,J＝7.4Hz,9H),0.93(t,J＝7.5Hz,3H).
13C NMR(151MHz,CDCl3)δ206.6,141.0,133.1,133.0,128.0,127.9,127.6,125.9,125.8,125.7,125.3,99.1,91.8,72.7,22.0,18.7,18.5,14.1,11.7.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C25H35Si:363.2508,found:363.2504.
[α]24 D＝+166.4(c＝0.5,CHCl3)
2,3-联烯醇I13的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALCEL OD-3 column(5％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:2.0min(major),2.9min(minor).
1H NMR(500MHz,CDCl3)δ7.13(d,J＝1.5Hz,1H),7.06(dd,J＝8.2,1.6Hz,1H),6.97(d,J＝8.2Hz,1H),5.13(d,J＝2.6Hz,1H),5.09(td,J＝6.9,2.0Hz,1H),2.34(d,J＝4.9Hz,1H),1.99(p,J＝7.4Hz,2H),1.20–1.10(m,3H),1.08(d,J＝7.2Hz,9H),0.98(d,J＝7.3Hz,9H),0.92(t,J＝7.5Hz,3H).
13C NMR(126MHz,CDCl3)δ206.8(s),143.7(s),143.0(s),140.3(s),131.6(t,J＝254.8Hz),122.2(s),108.6(s),108.4(s),99.2(s),92.0(s),72.2(s),21.9(s),18.6(s),18.5(s),14.1(s),11.7(s).
19F NMR(471MHz,CDCl3)δ-50.07(d,J＝97.4Hz),-50.40(d,J＝97.4Hz).
HRMS(ESI)m/z[M–H2O+H]+ calcd for C22H31SiF2O2:411.2167,found:411.2167.
[α]24 D＝+102.8(c＝0.5,CHCl3)
2,3-联烯醇I14的拆分条件及数据如下：
HPLC analysis:The ee was determined on a CHIRALCEL OD-3 column(5％i-PrOH in hexane,1.0mL/min)；retention times for compound obtained using(R,S)-Ld:3.7min(major),4.2min(minor).
1H NMR(500MHz,CDCl3)δ7.36(dd,J＝1.7,0.7Hz,1H),6.30(dd,J＝3.2,1.8Hz,1H),6.25(d,J＝3.2Hz,1H),5.22(td,J＝6.8,2.0Hz,1H),5.09(dd,J＝7.8,1.7Hz,1H),2.38(d,J＝7.9Hz,1H),2.13–2.03(m,2H),1.18–1.09(m,3H),1.07(d,J＝7.1Hz,9H),1.03(t,J＝7.5Hz,3H),0.99(d,J＝7.2Hz,9H).
13C NMR(126MHz,CDCl3)δ206.3,156.0,141.9,110.1,107.1,96.8,92.5,65.721.8,18.6,18.4,14.0,11.6.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C19H31SiO:303.2144,found:303.2148.
[α]24 D＝+216.4(c＝0.5,CHCl3)
2,3-联烯醇I15的拆分条件及数据如下：
HPLC analysis:The ee was determined on a CHIRALCEL OD-3 column(5％i-PrOH in hexane,1.0mL/min)；retention times for compound obtained using(R,S)-Ld:4.1min(major),4.5min(minor).
1H NMR(500MHz,CDCl3)δ7.23(dd,J＝5.0,1.0Hz,1H),7.02(d,J＝3.4Hz,1H),6.93(dd,J＝5.0,3.5Hz,1H),5.34(s,1H),5.20(td,J＝7.0,1.7Hz,1H),2.45(d,J＝5.1Hz,1H),2.17–2.08(m,2H),1.20–1.14(m,3H),1.09(d,J＝7.3Hz,9H),1.03(t,J＝7.4Hz,3H),0.99(d,J＝7.4Hz,9H).
13C NMR(126MHz,CDCl3)δ205.9,148.5,126.3,125.2,125.1,99.4,92.8,67.9,21.9,18.6,18.4,14.3,11.6.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C19H31SiS:319.1916,found:319.1914.
[α]24 D＝+219.2(c＝0.5,CHCl3)
2,3-联烯醇I16的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALCEL OD-3 column(5％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:1.4min(major),1.7min(minor).
1H NMR(500MHz,CDCl3)δ7.26–7.24(m,1H),7.19(d,J＝2.3Hz,1H),7.10(dd,J＝5.0,1.1Hz,1H),5.20(d,J＝1.3Hz,1H),5.13(td,J＝6.9,1.9Hz,1H),2.28(brs,1H),2.04(p,J＝7.4Hz,2H),1.20–1.11(m,3H),1.08(d,J＝7.2Hz,9H),0.99–0.97(m,12H).
13C NMR(126MHz,CDCl3)δ206.3,145.4,126.7,125.6,121.8,98.9,91.9,68.4,22.0,18.6,18.4,14.2,11.6.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C19H31SiS:319.1916,found:319.1899.
[α]24 D＝+196.4(c＝0.5,CHCl3)
2,3-联烯醇I17的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALCEL OD-3 column(5％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:4.3min(major),5.4min(minor).
1H NMR(500MHz,CDCl3)δ7.81(d,J＝7.8Hz,1H),7.74–7.69(m,1H),7.32(dtd,J＝16.4,7.2,1.3Hz,2H),7.24(s,1H),5.42(d,J＝4.2Hz,1H),5.21(td,J＝7.1,1.7Hz,1H),2.57(d,J＝5.9Hz,1H),2.19–2.11(m,2H),1.27–1.18(m,3H),1.13(d,J＝7.5Hz,9H),1.04–1.01(m,12H).
13C NMR(126MHz,CDCl3)δ206.4,149.3,139.9,139.3,124.0(two carbons),123.5,122.4,121.5,98.8,92.8,68.7,21.8,18.6,18.5,14.3,11.6.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C23H33SiS:369.2072,found:369.2073.
[α]24 D＝+215.2(c＝0.5,CHCl3)
2,3-联烯醇I18的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALPAK IG-3 column(10％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:2.2min(major),3.1min(minor).
1H NMR(500MHz,CDCl3)δ8.14(d,J＝6.1Hz,1H),7.71(d,J＝7.8Hz,1H),7.56(s,1H),7.31(t,J＝7.7Hz,1H),7.24(t,J＝7.5Hz,1H),5.37(d,J＝7.5Hz,1H),5.09(td,J＝7.1,1.5Hz,1H),2.12(d,J＝7.6Hz,1H),2.06–1.98(m,2H),1.65(s,9H),1.26–1.17(m,3H),1.11(d,J＝7.4Hz,9H),1.03(d,J＝7.4Hz,9H),0.93(t,J＝7.5Hz,3H).
13C NMR(126MHz,CDCl3)δ207.0,149.7,136.1,129.2,124.4,124.1,123.8,122.5,120.2,115.1,97.4,91.7,83.4,65.9,28.2,22.1,18.7,18.6,14.4,11.7.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C28H42SiO2N:452.2985,found:452.2987.
[α]24 D＝+306.8(c＝0.5,CHCl3)
2,3-联烯醇I19的拆分条件及数据如下：
HPLC analysis:The ee was determined on a CHIRALCEL OD-3 column(5％i-PrOH in hexane,1.0mL/min)；retention times for compound obtained using(R,S)-Ld:3.4min(major),3.8min(minor).
1H NMR(500MHz,CDCl3)δ5.08(td,J＝6.7,1.4Hz,1H),4.15–4.09(m,1H),2.72–2.55(m,2H),2.10(s,3H),2.03(dtd,J＝14.7,7.4,5.1Hz,2H),1.95(dddd,J＝14.1,8.6,7.4,3.4Hz,1H),1.79(dtd,J＝14.0,8.6,5.2Hz,1H),1.68(s,1H),1.22–1.13(m,3H),1.08(t,J＝7.2Hz,18H),1.02(t,J＝7.4Hz,3H).
13C NMR(126MHz,CDCl3)δ206.0,98.8,91.2,69.7,45.0,37.8,32.6(twocarbons),21.8,18.7,18.6,14.2,11.6.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C18H35SiS:311.2229,found:311.2227.
[α]24 D＝+14.4(c＝0.5,CHCl3)
2,3-联烯醇I20的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALPAK IG-3 column(3％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:5.4min(major),6.6min(minor).
1H NMR(500MHz,CDCl3)δ5.04(td,J＝6.7,1.3Hz,1H),3.98–3.93(m,1H),3.64(s,3H),2.27(t,J＝7.6Hz,2H),2.02(dtd,J＝14.7,7.4,4.1Hz,2H),1.58(dd,J＝14.3,7.1Hz,2H),1.47(tt,J＝13.3,4.6Hz,2H),1.32-1.22(m,10H),1.20–1.11(m,3H),1.10–1.03(m,18H),1.01(t,J＝7.4Hz,3H).
13C NMR(126MHz,CDCl3)δ206.1,174.3,98.9,91.0,70.0,51.4,38.8,34.1,29.5(twocarbons),29.2(two carbons),26.2,25.0,21.9,18.7(two carbons),14.3,11.7.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C25H47SiO2:407.3345,found:407.3344.
[α]24 D＝+11.2(c＝0.5,CHCl3)
2,3-联烯醇I21的拆分条件及数据如下：
HPLC analysis:The ee was determined on a CHIRALCEL OD-3 column(5％i-PrOH in hexane,1.0mL/min)；retention times for compound obtained using(R,S)-Ld:3.4min(major),4.0min(minor).
1H NMR(500MHz,CDCl3)δ5.07(t,J＝6.6Hz,1H),3.99(s,1H),3.53(t,J＝6.7Hz,2H),2.13–1.97(m,2H),1.86–1.75(m,2H),1.73–1.61(m,2H),1.58–1.45(m,3H),1.20–1.14(m,3H),1.08(t,J＝7.7Hz,18H),1.03(t,J＝7.4Hz,3H).
13C NMR(126MHz,CDCl3)δ206.0,98.8,91.2,69.7,45.0,37.8,32.6,23.6,21.8,18.7,18.6,14.2,11.6.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C19H36SiCl:327.2275,found:327.2245.
[α]24 D＝+22.4(c＝0.5,CHCl3)
2,3-联烯醇I22的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALPAK IG-3 column(5％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:2.8min(major),4.2min(minor).
1H NMR(500MHz,CDCl3)δ5.01(td,J＝7.1,1.1Hz,1H),4.14(brs,2H),3.78(t,J＝6.3Hz,1H),2.62(brs,2H),2.08–1.98(m,2H),1.89–1.82(m,1H),1.70–1.58(m,2H),1.44(s,9H),1.33(qd,J＝12.6,4.5Hz,1H),1.28–1.13(m,5H),1.07(dd,J＝10.3,7.3Hz,18H),1.02(t,J＝7.5Hz,3H).
13C NMR(126MHz,CDCl3)δ206.1,154.8,96.4,90.7,79.2,73.3,60.3,41.9,30.0,28.4,22.0,18.6(two carbons),14.5,11.6.
HRMS(APCI)m/z[M+H]+ calcd for C25H48NO3Si:438.3403,found:438.3406.
[α]24 D＝+29.6(c＝0.5,CHCl3)
2,3-联烯醇I23的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALPAK IG-3 column(5％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:1.6min(major),2.4min(minor).
1H NMR(500MHz,CDCl3)δ5.00(td,J＝7.1,1.4Hz,1H),4.02(dd,J＝11.3,4.0Hz,1H),4.00–3.94(m,1H),3.76(dd,J＝6.1,1.0Hz,1H),3.38–3.29(m,2H),2.07–1.99(m,2H),1.82–1.73(m,2H),1.58–1.36(m,4H),1.22–1.13(m,3H),1.08(dd,J＝9.7,7.3Hz,18H),1.02(t,J＝7.5Hz,3H).
13C NMR(126MHz,CDCl3)δ206.3,96.2,90.5,73.6,68.0,67.8,40.9,30.8,27.6,22.0,18.6(two carbons),14.5,11.6.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C20H37SiO:321.2614,found:321.2637.
[α]24 D＝+59.6(c＝0.5,CHCl3)
2,3-联烯醇I24的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALCEL OD-3 column(20％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:4.1min(major),5.1min(minor).
1H NMR(500MHz,CDCl3)δ7.99(s,1H),7.88(d,J＝8.5Hz,2H),7.84(s,1H),7.75(d,J＝8.4Hz,1H),7.63(d,J＝2.0Hz,1H),7.56(dd,J＝12.0,5.4Hz,2H),7.01(d,J＝8.4Hz,1H),5.35(s,1H),5.16(td,J＝6.8,1.7Hz,1H),3.91(s,3H),2.48(s,1H),2.23(s,6H),2.14(s,3H),2.11–2.03(m,2H),1.85(s,6H),1.26–1.18(m,3H),1.14(d,J＝7.3Hz,9H),1.02–0.97(m,12H).
13C NMR(126MHz,CDCl3)δ206.6,158.5,140.7,138.8(two carbons),133.3,133.1,131.9,128.3,128.0,125.8,125.7,125.6,125.5(two carbons),124.8,112.0,99.1,91.8,72.7,55.1,40.6,37.1(two carbons),29.1,22.0,18.7,18.5,14.1,11.7.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C42H55SiO:603.4022,found:603.4024.
[α]24 D＝+126.4(c＝0.5,CHCl3)
2,3-联烯醇I25的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALCEL OD-3 column(10％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:1.7min(major),2.3min(minor).
1H NMR(500MHz,CDCl3)δ7.73(d,J＝8.4Hz,2H),7.48(d,J＝8.3Hz,2H),5.21(s,1H),5.05(td,J＝6.8,1.9Hz,1H),3.05–3.00(m,4H),2.39(d,J＝4.5Hz,1H),1.92(p,J＝7.4Hz,2H),1.57–1.48(m,4H),1.19–1.09(m,3H),1.06(d,J＝7.3Hz,9H),0.97(d,J＝7.3Hz,9H),0.86(td,J＝7.4,1.5Hz,9H).
13C NMR(126MHz,CDCl3)δ207.3,148.4,138.8,127.4,126.8,99.0,91.8,72.2,50.0,22.0,21.7,18.6,18.5,14.0,11.7,11.1.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C27H46SiSNO2:476.3018,found:476.3025.
[α]24 D＝+82.8(c＝0.5,CHCl3)
2,3-联烯醇I26的拆分条件及数据如下：
The dr was determined on a CHIRALCEL OD-3 column(1％i-PrOH in hexane,1.0mL/min)；retention times for compound obtained using(R,S)-Ld:3.2min(major),3.4min(minor).
NMR spectra and HRMS for product from(R,S)-Ld:
1H NMR(500MHz,CDCl3)δ5.12–5.06(m,2H),4.08(d,J＝8.9Hz,1H),2.09–1.92(m,4H),1.77–1.69(m,1H),1.67(s,3H),1.60(s,3H),1.58–1.52(m,1H),1.41–1.27(m,3H),1.24–1.13(m,4H),1.08(t,J＝7.5Hz,18H),1.03(t,J＝7.4Hz,3H),0.91(d,J＝6.6Hz,3H).
13C NMR(126MHz,CDCl3)δ206.3,131.0,124.8,99.5,91.1,67.6,46.6,38.1,29.3,25.7,25.5,21.8,18.8,18.7(two carbons),17.6,14.2,11.6.
HRMS(ESI)m/z[M+H]+ calcd for C24H47SiO:379.3396,found:379.3369.
[α]24 D＝+9.2(c＝0.5,CHCl3)
2,3-联烯醇I27的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALPAK IB N-3 column(5％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:2.8min(major),3.4min(minor).
1H NMR(500MHz,CDCl3)δ7.04(d,J＝1.7Hz,1H),6.96(d,J＝8.0Hz,1H),6.92(dd,J＝8.1,1.7Hz,1H),5.13(brs,1H),5.10(td,J＝6.8,2.0Hz,1H),3.81(s,3H),2.28(s,3H),2.04–1.96(m,2H),1.18–1.11(m,3H),1.07(d,J＝7.3Hz,9H),0.97(d,J＝7.3Hz,9H),0.94(t,J＝7.5Hz,3H).
13C NMR(126MHz,CDCl3)δ206.6,168.9,150.8,142.6,139.0,122.1,119.4,111.1,99.0,91.7,72.3,55.7,21.9,20.6,18.6,18.5,14.1,11.6.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C24H37SiO3:401.2512,found:401.2512.
[α]24 D＝+110.8(c＝0.5,CHCl3)
2,3-联烯醇I28的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALPAK IA-3 column(5％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:1.8min(major),2.0min(minor).
1H NMR(500MHz,CDCl3)δ7.30(t,J＝7.5Hz,2H),7.25–7.17(m,3H),5.05(qd,J＝6.9,1.1Hz,1H),4.05(d,J＝3.9Hz,1H),2.86(ddd,J＝15.0,10.5,4.9Hz,1H),2.71(ddd,J＝13.6,10.3,6.5Hz,1H),2.02(tdd,J＝10.4,7.5,4.3Hz,1H),1.89–1.79(m,1H),1.69(d,J＝7.0Hz,3H),1.58(brs,1H),1.22–1.12(m,3H),1.08(t,J＝7.0Hz,18H).
13C NMR(126MHz,CDCl3)δ207.4,142.2,128.5,128.3,125.7,97.6,83.7,69.4,40.4,32.5,18.6(two carbons),13.6,11.5.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C22H35Si:327.2508,found:327.2492.
[α]24 D＝+38.4(c＝0.5,CHCl3)
2,3-联烯醇I29的拆分条件及数据如下：
HPLC analysis:The ee was determined on a CHIRALCEL OD-3 column(1％i-PrOH in hexane,0.5mL/min)；retention times for compound obtained using(R,S)-Ld:10.4min(major),11.4min(minor).
1H NMR(500MHz,CDCl3)δ7.27(t,J＝7.5Hz,2H),7.18(dd,J＝16.8,7.5Hz,3H),5.02(td,J＝7.6,1.4Hz,1H),4.05–3.99(m,1H),2.89–2.80(m,1H),2.68(ddd,J＝13.7,10.1,6.6Hz,1H),2.03–1.90(m,3H),1.87–1.78(m,1H),1.68–1.59(m,2H),1.19–1.10(m,3H),1.09–1.02(m,18H),0.92(d,J＝6.7Hz,6H).
13C NMR(126MHz,CDCl3)δ206.6,142.2,128.5,128.3,125.7,97.4,88.1,69.3,40.4,38.1,32.5,29.0,22.4,22.2,18.6,11.6.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C25H41Si:369.2978,found:369.2959.
[α]24 D＝+52.8(c＝0.5,CHCl3)
2,3-联烯醇I30的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALPAK IA-3 column(5％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:3.4min(major),3.9min(minor).
1H NMR(500MHz,CDCl3)δ7.31–7.28(m,4H),7.23–7.18(m,6H),5.08(td,J＝7.1,1.3Hz,1H),3.99(dd,J＝8.4,1.8Hz,1H),2.86–2.61(m,4H),2.46–2.30(m,2H),1.94(dddd,J＝13.7,10.1,6.7,3.4Hz,1H),1.72–1.60(m,1H),1.46(brs,1H),1.20–0.99(m,21H).
13C NMR(126MHz,CDCl3)δ206.1,142.1,141.5,128.5(two carbons),128.4,128.3,126.0,125.7,98.5,88.7,69.2,40.4,36.2,32.4,30.9,18.6,11.5.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C29H41Si:417.2987,found:417.2961.
[α]24 D＝+61.2(c＝0.5,CHCl3)
2,3-联烯醇I31的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALPAK IA-3 column(5％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:2.0min(major),2.2min(minor).
1H NMR(500MHz,CDCl3)δ7.29(t,J＝7.5Hz,2H),7.20(dd,J＝16.9,7.5Hz,3H),5.80(ddt,J＝16.9,10.2,6.6Hz,1H),5.07(td,J＝7.1,1.2Hz,1H),5.02(dd,J＝17.1,1.7Hz,1H),4.97(d,J＝10.2Hz,1H),4.04(d,J＝5.9Hz,1H),2.92–2.83(m,1H),2.71(ddd,J＝13.7,10.1,6.7Hz,1H),2.14–2.04(m,4H),2.04–1.96(m,1H),1.89–1.79(m,1H),1.60(brs,1H),1.53(p,J＝7.5Hz,2H),1.21–1.13(m,3H),1.12–1.03(m,18H).
13C NMR(126MHz,CDCl3)δ206.3,142.1,138.4,128.4,128.3,125.7,114.6,98.3,89.2,69.3,40.4,33.3,32.5,29.2,28.2,18.7,18.6,11.6.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C26H41Si:381.2978,found:381.3002.
[α]24 D＝+47.2(c＝0.5,CHCl3)
2,3-联烯醇I32的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALPAK IG-3 column(3％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:2.5min(major),2.9min(minor).
1H NMR(600MHz,CDCl3)δ7.38(d,J＝7.2Hz,2H),7.31(t,J＝7.6Hz,2H),7.24(t,J＝7.3Hz,1H),5.16(d,J＝1.1Hz,1H),5.03(dd,J＝7.0,2.1Hz,1H),2.30–2.23(m,2H),1.20–1.12(m,3H),1.09(d,J＝7.3Hz,9H),0.98(d,J＝7.4Hz,9H),0.94(d,J＝6.8Hz,3H),0.90(d,J＝6.8Hz,3H).
13C NMR(151MHz,CDCl3)δ205.4,143.7,128.0,127.4,127.1,100.1,97.7,72.7,28.5,22.9(two carbons),18.7,18.6,11.8.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C22H35Si:327.2508,found:327.2578.
[α]24 D＝+125.2(c＝0.5,CHCl3)
2,3-联烯醇I33的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALPAK IG-3 column(5％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:2.6min(major),3.1min(minor).
1H NMR(500MHz,CDCl3)δ7.39–7.36(m,2H),7.32(dd,J＝10.2,4.8Hz,2H),7.26–7.22(m,1H),5.18(dd,J＝7.2,2.0Hz,1H),5.16–5.13(m,1H),2.92–2.82(m,1H),2.32(d,J＝5.6Hz,1H),2.12–1.98(m,2H),1.89–1.78(m,1H),1.77–1.66(m,3H),1.18–1.11(m,3H),1.07(d,J＝7.3Hz,9H),0.97(d,J＝7.3Hz,9H).
13C NMR(126MHz,CDCl3)δ205.9,143.7,128.1,127.5,127.1,99.8,95.4,72.7,34.5,29.4,29.1,18.7,18.6,18.5,11.8.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C23H35Si:361.2328,found:361.2322.
[α]24 D＝+196.8(c＝0.5,CHCl3)
2,3-联烯醇I34的拆分条件及数据如下：
HPLC analysis:The ee was determined on a CHIRALCEL OD-3 column(3％i-PrOH in hexane,1.0mL/min)；retention times for compound obtained using(R,S)-Ld:5.3min(major),4.8min(minor).
1H NMR(500MHz,CDCl3)δ7.31–7.28(m,2H),7.22–7.18(m,3H),5.18(td,J＝6.2,2.4Hz,1H),4.20–4.12(m,1H),2.85–2.75(m,1H),2.70(ddd,J＝13.7,10.4,6.2Hz,1H),2.07–2.00(m,2H),2.00–1.93(m,1H),1.81(dddd,J＝13.1,10.4,7.6,5.2Hz,1H),1.71(d,J＝5.7Hz,1H),1.02(t,J＝7.4Hz,3H),0.13(s,9H).
13C NMR(126MHz,CDCl3)δ204.3,143.0,129.3,129.1,126.5,104.1,92.2,70.6,40.7,32.8,22.1,14.6,0.0.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C17H25Si:257.1725,found:257.1722.
[α]24 D＝+108.0(c＝0.5,CHCl3)
2,3-联烯醇I35的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALPAK IC-3 column(5％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:1.4min(major),1.2min(minor).
1H NMR(500MHz,CDCl3)δ7.31–7.27(m,2H),7.24–7.17(m,3H),5.15(td,J＝6.4,2.3Hz,1H),4.09(ddd,J＝7.6,3.8,2.3Hz,1H),2.86–2.78(m,1H),2.70(ddd,J＝13.7,10.3,6.3Hz,1H),2.09–2.01(m,2H),2.01–1.93(m,1H),1.84–1.74(m,1H),1.69(brs,1H),1.03(t,J＝7.4Hz,3H),0.95(t,J＝7.9Hz,9H),0.63(q,J＝7.9Hz,6H).
13C NMR(126MHz,CDCl3)δ204.1,142.2,128.5,128.3,125.7,100.1,91.2,69.6,40.0,32.1,21.6,14.0,7.3,3.6.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C20H31Si:299.2195,found:299.2188.
[α]24 D＝+45.6(c＝0.5,CHCl3)
2,3-联烯醇I36的拆分条件及数据如下：
HPLC analysis:The ee was determined on a CHIRALPAK IC-3 column(5％i-PrOH in hexane,1.0mL/min)；retention times for compound obtained using(R,S)-Ld:3.9min(major),3.7min(minor).
1H NMR(500MHz,CDCl3)δ7.29(t,J＝7.5Hz,2H),7.22–7.18(m,3H),5.16(td,J＝6.4,1.9Hz,1H),4.08(ddd,J＝7.8,3.8,1.8Hz,1H),2.83(ddd,J＝15.1,10.5,4.9Hz,1H),2.69(ddd,J＝13.7,10.3,6.4Hz,1H),2.11–2.02(m,2H),2.02–1.92(m,1H),1.86–1.75(m,1H),1.70(brs,1H),1.03(t,J＝7.4Hz,3H),0.92(s,9H),0.08(d,J＝12.1Hz,6H).
13C NMR(126MHz,CDCl3)δ204.9,142.2,128.5,128.3,125.7,101.1,91.7,69.6,40.3,32.3,26.7,21.6,17.9,13.9,-5.2,-5.5.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C20H31Si:299.2195,found:299.2180.
[α]24 D＝+46.0(c＝0.5,CHCl3)
2,3-联烯醇I37的拆分条件及数据如下：
SFC analysis:The ee was determined on a CHIRALPAK IC-3 column(5％i-PrOH in CO2,2.0mL/min)；retention times for compound obtained using(R,S)-Ld:5.0min(major),4.4min(minor).
1H NMR(500MHz,CDCl3)δ7.57(dd,J＝8.0,1.4Hz,6H),7.44–7.39(m,3H),7.37–7.34(m,6H),7.22–7.19(m,2H),7.15–7.12(m,1H),6.99(d,J＝7.0Hz,2H),5.13(td,J＝6.7,2.2Hz,1H),4.22–4.14(m,1H),2.70(ddd,J＝13.9,10.5,5.0Hz,1H),2.51(ddd,J＝13.6,10.3,6.3Hz,1H),1.96–1.79(m,3H),1.76–1.67(m,1H),1.65(d,J＝6.5Hz,1H),0.81(t,J＝7.4Hz,3H).
13C NMR(126MHz,CDCl3)δ207.2,142.0,136.1,133.8,129.6,128.4,128.2,127.8,125.6,99.2,92.8,69.9,39.7,32.2,21.5,13.8.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C32H31Si:443.2195,found:443.2201.
[α]24 D＝+7.6(c＝0.5,CHCl3)
2,3-联烯醇I38的拆分条件及数据如下：
HPLC analysis:The ee was determined on a CHIRALCEL OD-3 column(5％i-PrOH in hexane,1.0mL/min)；retention times for compound obtained using(R,S)-Ld:3.9min(major),4.4min(minor).
1H NMR(500MHz,CDCl3)δ7.37–7.33(m,2H),7.33–7.29(m,2H),7.26–7.22(m,1H),5.17(d,J＝2.5Hz,1H),5.14(td,J＝6.9,2.7Hz,1H),3.54(s,1H),2.39(s,1H),2.07–1.99(m,2H),1.43–1.35(m,2H),1.35–1.25(m,4H),0.99–0.98(m,3H),0.97–0.87(m,14H).
13C NMR(126MHz,CDCl3)δ204.6,143.1,128.1,127.5,126.8,97.9,90.5,74.0,31.4,29.4,28.6,22.5,18.6,18.5(two carbons),18.3,14.0,11.3,10.9.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C21H33Si:313.2351,found:313.2333.
[α]24 D＝+342.8(c＝0.5,CHCl3)
2,3-联烯醇I39的拆分条件及数据如下：
HPLC analysis:The ee was determined on a CHIRALPAK AD-3 column(5％i-PrOH in hexane,1.0mL/min)；retention times for compound obtained using(R,S)-Ld:5.6min(major),6.1min(minor).
1H NMR(500MHz,CDCl3)δ7.31–7.28(m,2H),7.23–7.17(m,3H),5.46(t,J＝6.1Hz,1H),4.10(dd,J＝7.8,5.0Hz,1H),2.85–2.76(m,1H),2.67(ddd,J＝13.8,10.1,6.5Hz,1H),2.10–2.01(m,2H),2.00–1.80(m,2H),1.08(s,9H),1.02(t,J＝7.4Hz,3H).
13C NMR(126MHz,CDCl3)δ198.8,142.2,128.4,128.3,125.7,119.2,98.2,68.2,40.2,33.2,32.6,29.6,22.3,13.5.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C18H25:241.1956,found:241.1958.
[α]24 D＝-3.2(c＝0.5,CHCl3)
实施例7：手性2,3-联烯醇参与的亲电环化反应构筑手性四氢呋喃类化合物。
Figure BDA0003289599520000201
化合物3的合成：
在25mL Schlenk管中称取化合物I38(330mg)，置换成氩气，注射器打入THF(10.0mL)，搅拌均匀，降温至零下78度，注射器滴加TBAF的四氢呋喃溶液(1.5mL，1.0M inTHF)。零下78度反应2小时。加入1.0mL的水淬灭反应，乙酸乙酯萃取，合并有机相，有机相用无水硫酸镁干燥，抽滤除去干燥剂，滤液用旋转蒸发仪脱除溶剂。残余物经硅胶柱层析(石油醚:乙酸乙酯＝10:1)得到白色固体3 175mg，收率为82％，dr值>20:1。
化合物3的数据：
1H NMR(500MHz,CDCl3)δ7.41–7.37(m,2H),7.37–7.32(m,2H),7.30–7.25(m,1H),5.42(dq,J＝9.0,3.0Hz,1H),5.37(qd,J＝6.6,2.5Hz,1H),5.21(dd,J＝5.9,2.4Hz,1H),2.16(brs,1H),2.09–2.00(m,2H),1.46–1.36(m,2H),1.36–1.24(m,4H),0.89(t,J＝7.0Hz,3H).
13C NMR(126MHz,CDCl3)δ202.0,143.1,128.4,127.7,126.2,96.2,95.4,72.2,31.3,28.8,28.7,22.5,14.0.
HRMS(ESI)m/z[M+H]+ calcd for C15H21O:217.1592,found:217.1599.
[α]24 D＝-46.4(c＝0.5,CHCl3)
化合物4的合成：
在25mL Schlenk管中称取化合物3(43mg)，置换成氩气，注射器打入MeCN(1.0mL)和水(0.1mL)，搅拌均匀，注射器滴加NBS的乙腈溶液(43mg NBS in 0.5mL MeCN)。室温下反应4小时。反应混合物用旋转蒸发仪脱除溶剂。残余物经硅胶柱层析(石油醚:乙酸乙酯＝10:1)得到白色固体4 39mg，收率为66％，dr值>20:1。
化合物4的数据：
1H NMR(500MHz,CDCl3)δ7.39–7.29(m,5H),6.03(t,J＝1.9Hz,1H),5.71(dd,J＝4.5,1.6Hz,1H),4.82(ddd,J＝10.0,5.1,2.9Hz,1H),1.97–1.87(m,1H),1.63(dddd,J＝13.9,10.6,7.8,4.8Hz,1H),1.58–1.41(m,2H),1.37–1.31(m,4H),0.90(t,J＝7.1Hz,3H).
13C NMR(126MHz,CDCl3)δ140.6,129.7,128.5,128.2,126.8,121.4,87.2,86.7,34.3,31.7,24.6,22.5,14.0.
HRMS(ESI)m/z[M–Br]+ calcd for C15H19O:215.1436,found:215.1427.
[α]24 D＝+53.3(c＝0.5,CHCl3).
化合物5的合成：
在25mL Schlenk管中称取化合物3(43mg)，置换成氩气，注射器打入丙酮(1.5mL)和水(1.0mL)，搅拌均匀，加入AgNO3(6.8mg)。室温下反应12小时。反应混合物用旋转蒸发仪脱除溶剂。残余物经硅胶柱层析(石油醚:乙酸乙酯＝10:1)得到白色固体5 39mg，收率为90％，dr值>20:1。
化合物5的数据：
1H NMR(600MHz,CDCl3)δ7.37–7.31(m,4H),7.31–7.25(m,1H),5.93(ddd,J＝6.0,2.4,1.4Hz,1H),5.86–5.82(m,1H),5.75(dd,J＝4.0,2.1Hz,1H),4.92–4.87(m,1H),1.74–1.61(m,2H),1.53–1.37(m,2H),1.36–1.28(m,4H),0.89(t,J＝7.1Hz,3H).
13C NMR(151MHz,CDCl3)δ142.1,130.6,130.0,128.4,127.6,126.6,87.5,86.6,36.8,31.9,25.4,22.6,14.0.
HRMS(ESI)m/z[M+H]+ calcd for C15H21O:217.1592,found:217.1596.
[α]24 D＝+111.2(c＝0.5,CHCl3).
实施例8：天然产物(+)-varitriol的形成合成。
Figure BDA0003289599520000211
化合物6的合成：
在手套箱中，二氯化铬与手性配体Ld在有机溶剂DME(乙二醇二甲醚)中室温下反应2小时，得到手性铬催化剂。随后将炔丙基卤化物(0.6mmol)、醛(0.4mmol)、锰粉(还原试剂)、二氯二茂锆(解离剂)依次按顺序加入含有手性铬催化剂中，室温下反应12小时。反应结束后，加入200uL水淬灭反应，旋转蒸发仪脱除溶剂后得粗产物。经短硅胶柱过滤除去催化剂、锰粉之后，用薄层层析或者核磁共振分析反应的转化率、收率、dr值，高效液相色谱分析产物的光学纯度，所得实验结果：化合物6的收率为47％，dr为7:1，ee值为96。化合物6的拆分条件及数据如下：
HPLC analysis:The ee was determined on a CHIRALPAK IC-3 column(5％i-PrOH in hexane,1.0mL/min)；retention times for compound obtained using(R,S)-Ld:4.7min(major),4.2min(minor).
1H NMR(500MHz,CDCl3)δ7.37–7.26(m,5H),5.01(qd,J＝7.0,2.4Hz,0.88H,major),4.98–4.93(m,0.11H,minor),4.60(s,0.15H),4.57(d,J＝2.5Hz,1.82H),4.34(dd,J＝7.4,3.2Hz,1H),3.66(s,1H),3.63(dd,J＝9.8,3.0Hz,1H),3.43(dd,J＝9.7,8.1Hz,1H),2.45(d,J＝4.0Hz,1H),1.64(d,J＝7.0Hz,3H),1.13–0.97(m,14H).
13C NMR(126MHz,CDCl3)δ207.1,138.0,128.4,127.7(two carbons),92.4,83.0,74.6,73.3,70.3,18.6,18.5(two carbons),13.5,11.3,11.00.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C19H29SiO:301.1988,found:301.1989.
[α]24 D＝–85.9(c＝0.5,CHCl3)
化合物7的合成：
在25mL Schlenk管中称取化合物6(159mg)，置换成氩气，注射器打入THF(10.0mL)，搅拌均匀，降温至零下78度，注射器滴加TBAF的四氢呋喃溶液(0.75mL，1.0M inTHF)。零下78度反应2小时。加入1.0mL的水淬灭反应，乙酸乙酯萃取，合并有机相，有机相用无水硫酸镁干燥，抽滤除去干燥剂，滤液用旋转蒸发仪脱除溶剂。残余物经硅胶柱层析(石油醚:乙酸乙酯＝10:1)得到白色固体7 88mg，收率为82％，dr值>20:1。
化合物7的数据：
1H NMR(500MHz,CDCl3)δ7.39–7.27(m,5H),5.30–5.22(m,1H),5.18(dq,J＝9.4,3.2Hz,1H),4.58(s,2H),4.36(ddd,J＝9.7,6.0,3.3Hz,1H),3.56(dd,J＝9.6,3.6Hz,1H),3.44(dd,J＝9.6,7.6Hz,1H),2.46(brs,1H),1.69(dd,J＝7.1,3.2Hz,3H).
13C NMR(126MHz,CDCl3)δ204.0,137.9,128.4,127.7(two carbons),91.0,88.7,74.2,73.4,68.7,14.1.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C13H15O:187.1123,found:187.1132.
[α]24 D＝+54.9(c＝0.5,CHCl3).
从化合物7出发，根据已知文献(DOI：10.1039/c2ob25069a)即可得到天然产物(+)-varitriol。

Claims (6)

1.一类同时含有轴手性和中心手性的2,3-联烯醇类化合物，其特征在于：具有式I的化合物或所述化合物的对映体、消旋体，
Figure FDA0003289599510000011
其中，R1选自C1～C10的烃基、苯基、取代苯基、1-萘基、2-萘基、杂芳基或苄基，所述取代苯基上的取代基为C1～C10的烃基、烷氧基、三氟甲基、卤素、硼酸基、巯基、氰基、酯基、磺酰基，取代基数量为1～5；所述杂芳基为呋喃基、噻吩基、苯丙噻吩基、吲哚基或吡啶基；
R2选自三烷基取代硅基、三芳基取代硅基、二烷基取代硅基、C1～C10的烃基、苯基、取代苯基、1-萘基、2-萘基、杂芳基或苄基，所述取代苯基上的取代基为C1～C10的烃基、烷氧基、三氟甲基、卤素、硼酸基、巯基、氰基、酯基、磺酰基，取代基数量为1～5；所述杂芳基为呋喃基、噻吩基、苯丙噻吩基、吲哚基或吡啶基；
R3选自C1～C10的烃基。
2.一类同时含有轴手性和中心手性的2,3-联烯醇类化合物的制备方法，其特征在于，以醛和炔丙基卤化物为起始原料经过下述反应式制备：
Figure FDA0003289599510000012
其中，炔丙基卤化物1、醛2、式I中R1～R3的含义与上述一致，X选自溴和氯。
3.根据权利要求2所述的一类同时含有轴手性和中心手性的2,3-联烯醇类化合物的制备方法，其特征在于，包括如下步骤：
在有机溶剂中，使用预先制备好的手性铬催化剂，与炔丙基卤化物1、醛2在还原试剂和解离试剂存在下发生反应得到式I所示的化合物。
4.根据权利要求3所述的一类同时含有轴手性和中心手性的2,3-联烯醇类化合物的制备方法，其特征在于，所述手性铬催化剂的制备方法为：由二氯化铬与选自手性配体La-Lk中任意一种在有机溶剂中室温下反应两个小时以上得到的；
Figure FDA0003289599510000021
5.根据权利要求3或4所述的一类同时含有轴手性和中心手性的2,3-联烯醇类化合物的制备方法，其特征在于，所述有机溶剂为乙二醇二甲醚、四氢呋喃、乙腈、甲苯、二甲苯、甲基叔丁基醚、乙醚、二氧六环、N,N-二甲基甲酰胺、二甲亚砜、二氯甲烷、氯仿、1,2-二氯乙烷中的一种或其中几种的混合溶剂；所述还原试剂为锰粉、锌粉、氢化铝锂、硼氢化钠、三乙酰氧基硼氢化钠、腈基硼氢化钠、三氯硅烷、苯硅烷中的一种；所述解离试剂为三甲基氯硅烷、三乙基氯硅烷、三苯基氯硅烷、二氯二茂锆中的一种。
6.一类同时含有轴手性和中心手性的2,3-联烯醇类化合物的应用，其特征在于，该2,3-联烯醇类化合物或所述化合物的对映体、消旋体通过亲电环化反应合成具有多手性中心的四氢呋喃类化合物和天然产物(+)-varitriol。
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