2, 3-allenol compounds containing both axial chirality and central chirality as well as preparation method and application thereof
阅读说明：本技术 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 (2, 3-allenol compounds containing both axial chirality and central chirality as well as preparation method and application thereof ) 是由 张丰华 王兆彬 于 2021-09-30 设计创作，主要内容包括：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。(The invention relates to a 2, 3-allenol compound containing both axial chirality and central chirality, and a preparation method and application thereof. The 2, 3-allenol compound is a compound with a formula I or an enantiomer and a racemate of the compound, and is mainly structurally characterized in that molecules simultaneously contain axial chirality and central chirality. The compound is synthesized by asymmetric addition of chromium-catalyzed propargyl halide and aldehyde compound. The 2, 3-dienolThe compounds have wide application and transformation in organic synthesis and have great practical value. In addition, the preparation method of the chiral 2, 3-allenol provided by the invention comprises the following steps: the method has the advantages of cheap and easily obtained reaction raw materials, simple and convenient reaction operation, wide application range of reaction substrates, easy amplification of reaction, mild reaction conditions and the like, and has practical value.)
1. A2, 3-allenol compound containing both axial chirality and central chirality is characterized in that: a compound having the formula I or an enantiomer, racemate of said compound,
wherein R is1The aryl group is selected from C1-C10 alkyl, phenyl, substituted phenyl, 1-naphthyl, 2-naphthyl, heteroaryl or benzyl, wherein the substituent on the substituted phenyl is C1-C10 alkyl, alkoxy, trifluoromethyl, halogen, boric acid group, sulfydryl, cyano, ester group and sulfonyl, and the number of the substituents is 1-5; the heteroaryl is furyl, thienyl, phenylpropylthiophenyl, indolyl or pyridyl;
R2the aryl-substituted aryl group is selected from trialkyl-substituted silicon base, triaryl-substituted silicon base, dialkyl-substituted silicon base, C1-C10 alkyl, phenyl, substituted phenyl, 1-naphthyl, 2-naphthyl, heteroaryl or benzyl, wherein the substituent on the substituted phenyl is C1-C10 alkyl, alkoxy, trifluoromethyl, halogen, boric acid group, sulfydryl, cyano, ester group and sulfonyl, and the number of the substituents is 1-5; the heteroaryl is furyl, thienyl, phenylpropylthiophenyl, indolyl or pyridyl;
R3selected from C1-C10 hydrocarbon groups.
2. A preparation method of 2, 3-allenol compounds containing both axial chirality and central chirality is characterized in that aldehyde and propargyl halide are used as starting materials and prepared by the following reaction formula:
wherein propargyl halide 1, aldehyde 2, R in formula I1～R3The meaning of (A) is identical to that described above, X being selected from bromine and chlorine.
3. The preparation method of 2, 3-allenol compounds containing both axial chirality and central chirality according to claim 2, comprising the steps of:
in an organic solvent, a chiral chromium catalyst prepared in advance is used to react with propargyl halide 1 and aldehyde 2 in the presence of a reducing agent and a dissociation reagent to obtain the compound shown in the formula I.
4. The preparation method of 2, 3-allenol compounds containing both axial chirality and central chirality according to claim 3, wherein the preparation method of the chiral chromium catalyst comprises: the catalyst is obtained by reacting chromium dichloride and any one of chiral ligands La-Lk in an organic solvent at room temperature for more than two hours;
5. the preparation method of 2, 3-allene alcohol compounds containing both axial chirality and central chirality according to claim 3 or 4, wherein the organic solvent is one or more of ethylene glycol dimethyl ether, tetrahydrofuran, acetonitrile, toluene, xylene, methyl tert-butyl ether, diethyl ether, dioxane, N-dimethylformamide, dimethyl sulfoxide, dichloromethane, chloroform, 1, 2-dichloroethane; the reducing reagent is one of manganese powder, zinc powder, lithium aluminum hydride, sodium borohydride, sodium triacetoxyborohydride, sodium cyanoborohydride, trichlorosilane and phenylsilane; the dissociation reagent is one of trimethylchlorosilane, triethylchlorosilane, triphenylchlorosilane and zirconocene dichloride.
6. The application of the 2, 3-dienol compound containing both axial chirality and central chirality is characterized in that the 2, 3-dienol compound or enantiomer and racemate of the compound are subjected to electrophilic cyclization reaction to synthesize the tetrahydrofuran compound with multi-chiral center and a natural product (+) -varritiol.
Technical Field
The invention belongs to the technical field of organic synthesis, and relates to a 2, 3-dienol compound containing both axial chirality and central chirality, and a preparation method and application thereof.
Background
2, 3-allenes are a class of compounds containing both allenes (1, 2-dienes) and hydroxyl groups. The structure of the compound contains two active groups simultaneously, so that the compound has high reaction activity, and can perform transition metal catalyzed self-isomerization cyclization reaction, palladium catalyzed coupling reaction, ruthenium catalyzed cyclocarbonylation reaction, ring expansion reaction, cyclization reaction with electrophilic reagents, intramolecular ring addition reaction, free radical reaction, reaction for generating allene or 1, 3-conjugated diene based on methylene-pi-allyl palladium intermediate under catalysis of zero-valent palladium, rearrangement reaction and the like, and therefore the compound occupies an important position in organic synthesis. For example, 2, 3-dienols are not only important intermediates for the synthesis of some natural products, such as (+) -Varitiol, Boivinianin B, Amphiinolide X, (+) -Furanomycin, etc.; also are synthesis precursors of some important organic compounds, such as 2, 5-dihydrofuran compounds, alkenyl epoxy compounds, 2(5H) -furanones, alpha, beta-unsaturated ketones, and the like.
The main methods for synthesizing chiral 2, 3-dienols at present include the following three methods: one is the enzyme-catalyzed kinetic resolution of racemic 2, 3-dienol, and the enzyme generally has stronger specificity to a substrate, so the substrate structure in the method is relatively single, and the method can only be used for synthesizing the 2, 3-dienol with single-center chirality, so the universality and the applicability of the method are lower. Secondly, chiral raw materials are used for synthesizing chiral 2, 3-allenol, and the used chiral raw materials need complicated preparation and purification, so that the applicable substrate has larger limitation, and the method has poor practicability. Thirdly, chiral catalyst is used for catalyzing asymmetric synthesis. The method can convert various substrates into chiral 2, 3-dienol by using the chiral catalyst with catalytic amount, and the reaction has better universality and higher efficiency. Of these methods, most of them can be used only for the preparation of 2, 3-dienols having a single central chirality, as reported by Yamamoto group (DOI:10.1021/ja0679578), Reddy group (DOI:10.1039/c2cc34371a), Ohmiya group (DOI:10.1039/d0cc02619k), and the like. 2, 3-allenol compounds containing both axial chirality and central chirality and preparation methods thereof are few in reports at present. In 2016, the List topic group achieved the synthesis of a class of chiral 2, 3-dienols using alkynyl-substituted ketene acetals and aryl aldehydes as substrates and bis-sulfonylimides as catalysts (DOI: 10.1002/anie.201603649). In 2016 and 2018, the Feng group of subjects used isatin as a substrate, and used chiral gold and copper catalysts, respectively, to achieve synthesis of chiral 2, 3-dienols containing the isatin structure (DOI: 10.1021/acscatal.6b00294 and DOI:10.1016/j. chempr.2018.04.012). In 2020, the Yin project group reports that copper catalyzes the addition reaction of propargyl ester to aldehyde and also realizes the synthesis of chiral 2, 3-allenol (DOI: 10.1002/anie.201912140). However, the above methods all use some special activated substrates, and therefore the product structure has a large limitation, such as the allene fragment must contain ester functional groups. These methods are not available for the chiral 2, 3-dienols synthesized in the present patent as simple alkyl-substituted products in the dienyl fragment.
The key to developing a universal synthetic method and preparing a 2, 3-allenol compound containing both axial chirality and central chirality from simple raw materials is to find a suitable chiral metal catalyst.
Disclosure of Invention
The invention aims to provide a preparation method of 2, 3-allenol compounds containing both axial chirality and central chirality. The 2, 3-allenol compound containing both axial chirality and central chirality provided by the invention is a compound with a formula I or an enantiomer and a racemate of the compound.
Wherein R is1Is selected from C1-C10 alkyl, phenyl, substituted phenyl, 1-naphthyl, 2-naphthyl, heteroaryl or benzyl, wherein the substituent on the phenyl is C1-C10 alkyl,Alkoxy, trifluoromethyl, halogen, boric acid group, sulfydryl, cyano, ester group and sulfonyl, wherein the number of the substituents is 1-5, and the heteroaryl is furyl, thienyl, phenylpropylthiophenyl, indolyl or pyridyl;
R2the aryl group is selected from trialkyl substituted silicon base, triaryl substituted silicon base, dialkyl substituted silicon base, C1-C10 alkyl, phenyl, substituted phenyl, 1-naphthyl, 2-naphthyl, heteroaryl or benzyl, wherein the substituent on the phenyl is C1-C10 alkyl, alkoxy, trifluoromethyl, halogen, boric acid group, sulfydryl, cyano, ester group and sulfonyl, the number of the substituents is 1-5, and the heteroaryl is furyl, thienyl, phenylpropylthiophenyl, indolyl or pyridyl;
R3selected from C1-C10 hydrocarbon groups.
The invention provides a preparation method of a 2, 3-dienol compound containing both axial chirality and central chirality, which is prepared by taking aldehyde and propargyl halide as starting materials through the following reaction formula:
wherein propargyl halide 1, aldehyde 2, R in formula I1～R3The meaning of (A) is identical to that described above, X being selected from bromine and chlorine. The compounds shown as propargyl halide 1 and the compounds shown as aldehyde 2 were prepared according to literature procedures. The preparation method of the 2, 3-allenol compound containing both axial chirality and central chirality comprises the following steps:
in an organic solvent, a chiral chromium catalyst prepared in advance is used to react with propargyl halide 1 and aldehyde 2 in the presence of a reducing agent and a dissociating agent to obtain the compound shown in the formula I.
In the above synthesis method, the preparation method of the chiral chromium catalyst comprises: the compound is obtained by reacting chromium dichloride and any one of chiral ligands La-Lk in an organic solvent for more than two hours at room temperature.
Preferably, the specific operations of the synthesis method are as follows: in a glove box, reacting chromium dichloride and the chiral ligand La-Lk in an organic solvent for 2 hours at room temperature to obtain the chiral chromium catalyst. And then sequentially adding the propargyl halide 1, the aldehyde 2, the reducing reagent and the dissociating agent into a catalyst containing chiral chromium, reacting for 12 hours at room temperature, and performing column chromatography separation to obtain the chiral 2, 3-dienol.
In the synthesis method, the organic solvent can be one or a mixture of more of ethylene glycol dimethyl ether, tetrahydrofuran, acetonitrile, toluene, xylene, methyl tert-butyl ether, diethyl ether, dioxane, N-dimethylformamide, dimethyl sulfoxide, dichloromethane, chloroform and 1, 2-dichloroethane; the reducing reagent can be one of manganese powder, zinc powder, lithium aluminum hydride, sodium borohydride, sodium triacetoxyborohydride, sodium cyanoborohydride, trichlorosilane and phenylsilane; the dissociating agent can be one of trimethylchlorosilane, triethylchlorosilane, triphenylchlorosilane and zirconocene dichloride.
Compared with the prior art, the invention has the following effects:
1) the chiral 2, 3-dienol provided by the invention contains both axial chirality and central chirality, and the products have wide application and transformation in organic synthesis and have great practical value.
2) The preparation method of the chiral 2, 3-allenol provided by the invention comprises the following steps: the method has the advantages of cheap and easily obtained reaction raw materials, simple and convenient reaction operation, wide application range of reaction substrates, easy amplification of reaction, mild reaction conditions and the like, and can realize industrial production and application. .
3) The chiral 2, 3-dienol provided by the invention synthesizes the tetrahydrofuran compound with multi-chiral center and the natural product (+) -variritiol through electrophilic cyclization reaction.
Detailed Description
The present invention will now be described more fully hereinafter with reference to the following examples, which are set forth to provide an understanding of the present invention, but are not to be construed as limiting the scope of the present invention.
Example 1: effect of ligand La on the reaction
In a glove box, reacting chromium dichloride and a chiral ligand La in an organic solvent DME (ethylene glycol dimethyl ether) for 2 hours at room temperature to obtain the chiral chromium catalyst. Then propargyl halide 1(0.6mmol), benzaldehyde 2(0.4mmol), manganese powder (reducing agent) and zirconocene dichloride (dissociating agent) are sequentially added into the catalyst containing chiral chromium and reacted for 12 hours at room temperature. After the reaction is finished, adding 200uL of water to quench the reaction, and removing the solvent by a rotary evaporator to obtain a crude product. After the catalyst and manganese powder are removed by short silica gel column filtration, the conversion rate, yield and dr value of the reaction are analyzed by thin layer chromatography or nuclear magnetic resonance, the optical purity of the product is analyzed by high performance liquid chromatography, and the experimental result is obtained: the yield was 86%, dr >20:1, ee 92.
Example 2: effect of ligand Lc on the reaction
In a glove box, reacting chromium dichloride and a chiral ligand Lc in an organic solvent DME (ethylene glycol dimethyl ether) for 2 hours at room temperature to obtain the chiral chromium catalyst. Then propargyl halide 1(0.6mmol), benzaldehyde 2(0.4mmol), manganese powder (reducing agent) and zirconocene dichloride (dissociating agent) are sequentially added into the catalyst containing chiral chromium and reacted for 12 hours at room temperature. After the reaction is finished, adding 200uL of water to quench the reaction, and removing the solvent by a rotary evaporator to obtain a crude product. After the catalyst and manganese powder are removed by short silica gel column filtration, the conversion rate, yield and dr value of the reaction are analyzed by thin layer chromatography or nuclear magnetic resonance, the optical purity of the product is analyzed by high performance liquid chromatography, and the experimental result is obtained: the yield was 82%, dr was 10:1 and ee value was 72.
Example 3: effect of ligand Le on the reaction
In a glove box, reacting chromium dichloride and a chiral ligand Le in an organic solvent DME (ethylene glycol dimethyl ether) for 2 hours at room temperature to obtain the chiral chromium catalyst. Then propargyl halide 1(0.6mmol), benzaldehyde 2(0.4mmol), manganese powder (reducing agent) and zirconocene dichloride (dissociating agent) are sequentially added into the catalyst containing chiral chromium and reacted for 12 hours at room temperature. After the reaction is finished, adding 200uL of water to quench the reaction, and removing the solvent by a rotary evaporator to obtain a crude product. After the catalyst and manganese powder are removed by short silica gel column filtration, the conversion rate, yield and dr value of the reaction are analyzed by thin layer chromatography or nuclear magnetic resonance, the optical purity of the product is analyzed by high performance liquid chromatography, and the experimental result is obtained: the yield was 92%, dr was 4:1 and ee was 55.
Example 4: effect of ligand Lh on the reaction
In a glove box, reacting chromium dichloride and a chiral ligand Lh in an organic solvent DME (ethylene glycol dimethyl ether) at room temperature for 2 hours to obtain the chiral chromium catalyst. Then propargyl halide 1(0.6mmol), benzaldehyde 2(0.4mmol), manganese powder (reducing agent) and zirconocene dichloride (dissociating agent) are sequentially added into the catalyst containing chiral chromium and reacted for 12 hours at room temperature. After the reaction is finished, adding 200uL of water to quench the reaction, and removing the solvent by a rotary evaporator to obtain a crude product. After the catalyst and manganese powder are removed by short silica gel column filtration, the conversion rate, yield and dr value of the reaction are analyzed by thin layer chromatography or nuclear magnetic resonance, the optical purity of the product is analyzed by high performance liquid chromatography, and the experimental result is obtained: the yield was 90%, dr was 4:1 and ee was 77.
Example 5: effect of ligand Ld on the reaction
In a glove box, reacting chromium dichloride and a chiral ligand Ld in an organic solvent DME (ethylene glycol dimethyl ether) for 2 hours at room temperature to obtain the chiral chromium catalyst. Then propargyl halide 1(0.6mmol), benzaldehyde 2(0.4mmol), manganese powder (reducing agent) and zirconocene dichloride (dissociating agent) are sequentially added into the catalyst containing chiral chromium and reacted for 12 hours at room temperature. After the reaction is finished, adding 200uL of water to quench the reaction, and removing the solvent by a rotary evaporator to obtain a crude product. After the catalyst and manganese powder are removed by short silica gel column filtration, the conversion rate, yield and dr value of the reaction are analyzed by thin layer chromatography or nuclear magnetic resonance, the optical purity of the product is analyzed by high performance liquid chromatography, and the experimental result is obtained: the yield was 88%, dr >20:1, ee 98. The resolution conditions and data for this 2, 3-dienol I1 are as follows:
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).
example 6: synthesis of chiral 2, 3-dienols
In a glove box, reacting chromium dichloride and a chiral ligand Ld in an organic solvent DME (ethylene glycol dimethyl ether) for 2 hours at room temperature to obtain the chiral chromium catalyst. Then propargyl halide 1(0.6mmol), aldehyde 2(0.4mmol), manganese powder (reducing agent) and zirconocene dichloride (dissociating agent) are sequentially added into the catalyst containing chiral chromium and reacted for 12 hours at room temperature. After the reaction is finished, adding 200uL of water to quench the reaction, and removing the solvent by a rotary evaporator to obtain a crude product. After the catalyst and manganese powder are removed by short silica gel column filtration, the conversion rate, yield and dr value of the reaction are analyzed by thin layer chromatography or nuclear magnetic resonance, and the optical purity of the product is analyzed by high performance liquid chromatography, and the obtained experimental results are shown in table 1.
TABLE 12 asymmetric catalytic Synthesis of 3-dienols
The resolution conditions and data for 2, 3-dienol I2 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I3 are as follows:
SFC analysis:The ee was determined on a CHIRALCEL OD-3 column(5％MeOH in 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)
the resolution conditions and data for 2, 3-dienol I4 are as follows:
SFC analysis:The ee was determined on a CHIRALCEL OD-3 column(5％MeOH in 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)
the resolution conditions and data for 2, 3-dienol I5 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I6 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I7 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I8 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I9 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I10 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I11 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I12 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I13 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I14 are as follows:
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)δ206.3,156.0,141.9,110.1,107.1,96.8,92.5,65.7 21.8,18.6,18.4,14.0,11.6.
HRMS(ESI)m/z[M–H2O+H]+ calcd for C19H31SiO:303.2144,found:303.2148.
[α]24 D＝+216.4(c＝0.5,CHCl3)
the resolution conditions and data for 2, 3-dienol I15 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I16 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I17 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I18 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I19 are as follows:
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(two carbons),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)
the resolution conditions and data for 2, 3-dienol I20 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I21 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I22 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I23 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I24 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I25 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I26 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I27 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I28 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I29 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I30 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I31 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I32 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I33 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I34 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I35 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I36 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I37 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I38 are as follows:
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)
the resolution conditions and data for 2, 3-dienol I39 are as follows:
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)
example 7: chiral 2, 3-dienol participates in electrophilic cyclization reaction to construct chiral tetrahydrofuran compounds.
Synthesis of Compound 3:
compound I38(330mg) was weighed into a 25mL Schlenk tube, replaced with argon, THF (10.0mL) was added via syringe, stirred well, cooled to-78 deg.C, and TBAF in tetrahydrofuran (1.5mL, 1.0M in THF) was added dropwise via syringe. Reaction at-78 deg.c for 2 hr. Adding 1.0mL of water to quench the reaction, extracting with ethyl acetate, combining organic phases, drying the organic phases with anhydrous magnesium sulfate, filtering to remove the drying agent, and removing the solvent from the filtrate by using a rotary evaporator. Chromatography of the residue on a silica gel column (petroleum ether: ethyl acetate 10:1) gave 3175 mg of a white solid in 82% yield with a dr value >20: 1.
Data for compound 3:
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)
synthesis of Compound 4:
compound 3(43mg) was weighed in a 25mL Schlenk tube, replaced with argon, MeCN (1.0mL) and water (0.1mL) were added to the tube via a syringe, and the mixture was stirred well, and an acetonitrile solution of NBS (43mg NBS in 0.5mL MeCN) was added dropwise to the tube via a syringe. The reaction was carried out at room temperature for 4 hours. The reaction mixture was stripped of solvent using a rotary evaporator. Chromatography of the residue on a silica gel column (petroleum ether: ethyl acetate ═ 10:1) afforded 439 mg of a white solid in 66% yield with a dr value >20: 1.
Data for compound 4:
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).
synthesis of Compound 5:
compound 3(43mg) was weighed in a 25mL Schlenk tube, replaced with argon, acetone (1.5mL) and water (1.0mL) were added to the tube via a syringe, and AgNO was added thereto after stirring the mixture to be uniform3(6.8 mg). The reaction was carried out at room temperature for 12 hours. The reaction mixture was stripped of solvent using a rotary evaporator. The residue was subjected to silica gel column chromatography (petroleum ether: ethyl acetate 10:1) to give a white solid539 mg, yield 90%, dr value>20:1。
Data for compound 5:
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).
example 8: formation and synthesis of the natural product (+) -variritiol.
Synthesis of Compound 6:
in a glove box, reacting chromium dichloride and a chiral ligand Ld in an organic solvent DME (ethylene glycol dimethyl ether) for 2 hours at room temperature to obtain the chiral chromium catalyst. Then propargyl halide (0.6mmol), aldehyde (0.4mmol), manganese powder (reducing agent) and zirconocene dichloride (dissociating agent) are sequentially added into the catalyst containing chiral chromium and reacted for 12 hours at room temperature. After the reaction is finished, adding 200uL of water to quench the reaction, and removing the solvent by a rotary evaporator to obtain a crude product. After the catalyst and manganese powder are removed by short silica gel column filtration, the conversion rate, yield and dr value of the reaction are analyzed by thin layer chromatography or nuclear magnetic resonance, the optical purity of the product is analyzed by high performance liquid chromatography, and the experimental result is obtained: the yield of compound 6 was 47%, dr was 7:1, and ee was 96. The resolution conditions and data for compound 6 are as follows:
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)
synthesis of compound 7:
compound 6(159mg) was weighed into a 25mL Schlenk tube, replaced with argon, THF (10.0mL) was added via syringe, stirred well, cooled to-78 deg.C, and TBAF in tetrahydrofuran (0.75mL, 1.0M in THF) was added dropwise via syringe. Reaction at-78 deg.c for 2 hr. Adding 1.0mL of water to quench the reaction, extracting with ethyl acetate, combining organic phases, drying the organic phases with anhydrous magnesium sulfate, filtering to remove the drying agent, and removing the solvent from the filtrate by using a rotary evaporator. The residue was chromatographed on a silica gel column (petroleum ether: ethyl acetate 10:1) to give 788 mg of a white solid in 82% yield with a dr value >20: 1.
Data for compound 7:
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).
starting from compound 7, the natural product, (+) -variritiol, is obtained according to the known literature (DOI:10.1039/c 2ob25069 a).