CN101565393B - 3-(substituted bisulfonyl fluromethane)-1-propylene compound, synthetic method and applications thereof - Google Patents
3-(substituted bisulfonyl fluromethane)-1-propylene compound, synthetic method and applications thereof Download PDFInfo
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Abstract
The invention provides a 3-(substituted bisulfonyl fluromethane)-1-propylene compound, a synthetic method and applications thereof. The method is an effective method for synthesizing the optically active 3-(substituted bisulfonyl fluromethane)-1-propylene compound with iridium complex as catalyst and allyl carbonic ester and diphenylsulfonyl fluomethane compound in a highly regional and highly enantioselective manner. The catalyst is easy to obtain and has high activity; the reaction conditions are mild; a substrate has a wide application range and the products have high regional and enantioselectivity. The synthesized 3-(substituted bisulfonyl fluromethane)-1-propylene compound is easy for preparing fluorochemicals which contain aldehyde, alcohol, amine, carboxylic acid or poly-cycle, arewidely applied to pesticides and drugs and have special physiological activities in a chemical way.
Description
Technical field
The present invention relates to a kind of by metal according to the disulfonyl base fluoromethanes of complex catalysis and the allyl group alkylated reaction of allyl carbonate, this reaction can high-level efficiency, high zone and enantioselectivity ground synthesize 3-disulfonyl base fluoromethane replacement-1-propene compound.The present invention relates to 3-disulfonyl base fluoromethane replacement-1-propene compound through removing the synthetic pharmaceutical intermediate with special physiological effect that contains aldehyde, aldehyde, alcohol, amine, carboxylic acid or the polynary ring of single fluoro methyl of the chemistry routes such as alkylsulfonyl, oxidation, two ammonification, cyclisation.
Background technology
In medicinal design, medicinal design has great significance for isostere in single methyl fluoride building block, contain a single fluoro methyl group unit in the compound and have important effect [a) Organofluorine Chemistry:Principles and Commercial Applications (Eds.:Banks, R.E.; Smart, B.E.; Tatlow, J.C.), Plenum, New York, 1994, chap.3; B) Hudlicky, M.; Pavlath, A.E.; Chemistry ofOrganic Fluorine Compounds II.A Critical Review ACS Monograph 187, AmericanChemical Society, Washington, DC, 1995; C) Biomedical Fontiers of FluorineChemistry (Eds.:Ojima, I.; McCarthy, J.R.; Welch, J.T.), Washington, DC, 1996; D) Organofluorine Compounds.Chemistry and Applications (Ed:Hiyama, T.), Springer, New York, 2000; E) Smart, B.E.J.Fluorine Chem.2001,109,3; F) Thayer, A.M.Chem.Eng.News 2006,84,15-24,27-32; F) M ü ller, K.Faeh, C.Diederich, F.Science 2007,317, and 1881.].Yet, directly introduce single methyl fuoride in the compound and be difficulty relatively.In recent years, people have designed the equivalents of hexichol alkylsulfonyl methyl fuoride as single fluoro methyl, come synthetic special compound [(a) Ni, the C. that contains the building block of single fluoro methyl; Li, Y.; Hu, J.J.Org.Chem.2006,71,6829. (b) Ni, C.; Zhang, L.; Hu, J.J.Org.Chem.2008,73,5699. (c) Prakash, S.G.K.; Chacko, S.; Alconcel, S.; Stewart, T.; Mathew, T.; Olah, G.A.Angew.Chem., Int.Ed.2007,46,4933. (d) Mizuta, S.; Shibata, N.; Goto, Y.; Furukawa, T.; Nakamura, S.; Toru, T.J.Am.Chem.Soc.2007,129,6394.] people have also realized the asymmetric allylation take hexichol fluorosulfonyl methane as nucleophilic reagent of catalyzing by metal palladium, have obtained very high yield and enantioselectivity [Fukuzumi, T.; Shibata, N.; Sugiura, M.; Yasui, H.; Nakamura, N.; Toru, T.Angew.Chem., Int.Ed.2006,45,4973.].Not only can not solve this difficult problem of regioselectivity with palladium catalytic system, and product is when the derivatize reduction removes this alkylsulfonyl, because the existence of conjugated double bond tends to a reduction.In order to address this problem; we have invented the allyl substitution reaction take disulfonyl base methyl fuoride as nucleophilic reagent by metal iridium catalysis; this reaction can realize that not only high zone and high enantioselectivity ground synthesize 3-disulfonyl base fluoromethane replacement-1-propene compound; and when derivatize removes alkylsulfonyl; more succinct, Atom economy is higher.In view of containing simultaneously the methyl building block of disulfonyl base fluoro and terminal double link in this product; be easy to generate by simple derivatize the compounds such as the acid that contains single fluoro methyl group unit, aldehyde, alcohol, amine, polynary ring, so the method there is very important meaning to synthetic this type of compound.
Summary of the invention
The purpose of this invention is to provide a kind of 3-disulfonyl base fluoromethane replacement-1-propene compound.
Purpose of the present invention also provides a kind of method of effectively synthetic 3-disulfonyl base fluoromethane replacement-1-propene compound.
Another object of the present invention provides a kind of purposes of above-mentioned 3-disulfonyl base fluoromethane replacement-1-propene compound.
The structural formula of 3-disulfonyl base fluoromethane replacement-1-propene compound of the present invention is:
R wherein
1Be selected from arbitrarily C
1-C
16Alkyl, C
3-C
16Cycloalkyl, C
4-C
10The heterocyclic radical that contains N, O or S or C
4-C
10The heteroaryl that contains N, O or S, aryl or the aryl that replaces of R; R is C
1-C
4Alkyl, C
1-C
4Perfluoroalkyl, halogen or C
1-C
4Alkoxyl group.
R
2Be selected from arbitrarily C
1-C
16Alkyl, C
3-C
16Cycloalkyl, C
4-C
10The heterocyclic radical that contains N, O or S or C
4-C
10The heteroaryl that contains N, O or S, aryl;
Described aryl is phenyl or naphthyl.
Method of the present invention is a kind of method of effectively synthesizing 3-disulfonyl base fluoromethane replacement-1-propene compound by hexichol alkylsulfonyl methyl fuoride (FBSM) compounds and allyl carbonate ester compound.
Method of the present invention be a kind of effectively with iridium complex as catalyzer, by the method for the synthetic 3-disulfonyl base fluoromethane replacement-1-propene compound of hexichol fluorosulfonyl band methane (FBSM) compounds and allyl carbonate ester compound.
Method of the present invention be a kind of effectively by the chiral iridium complex compound as catalyzer, by the method for the pure 3-disulfonyl base fluoromethane replacement-1-propene compound of hexichol fluorosulfonyl band methane (FBSM) compounds and allyl carbonate ester compound synthesizing optical.
The chirality 3-disulfonyl base fluoromethane replacement-1-propene compound that the present invention synthesized is through the synthetic compound that contains aldehyde, aldehyde, alcohol, amine, carboxylic acid or the polynary ring of fluorine atom of chemistry route; have unique physiologically active, be widely used among medicine and the agricultural chemicals.
3-disulfonyl base fluoromethane replacement-1-propene compound of the present invention is as raw material, in the presence of organic solvent, with [Ir (COD) Cl] take hexichol fluorosulfonyl methane compound and allyl carbonate ester compound
2The iridium complex that generates with the chiral ligand effect is as catalyzer, reacts to make under the effect of alkali, can be represented by the formula:
Wherein L is chiral ligand, and Base is the combination of various alkali mentioned above and alkali and additive, and Solv. is all kinds of SOLVENTS mentioned above, and LG is leavings group, is methyl carbonate, ethyl ester, carbonic acid tertiary butyl ester etc.
Allyl carbonate ester compound structural formula is:
, hexichol fluorosulfonyl methane compound structural formula is:
R wherein
1, R
2Be selected from arbitrarily C
1-C
16Alkyl, C
3-C
16Cycloalkyl, C
4-C
10The heterocyclic radical that contains N, O or S or C
4-C
10The aryl that replaces of the heteroaryl that contains N, O or S, aryl, R; Described aryl is phenyl or naphthyl; R is C
1-C
4Alkyl, C
1-C
4Perfluoroalkyl, halogen or C
1-C
4Alkoxyl group; LG is leavings group.
The ligand structure formula is any optically pure structure, not limit by following diagram, as:
Wherein, R
3, R
4, R
5Be selected from arbitrarily C
3-C
16Alkyl, cycloalkyl; Phenyl, naphthyl, C
1-C
4The alkoxyl group phenyl or the C that replace
1-C
4The naphthyl that replaces of alkoxyl group.
Described alkali is triethylamine, 1,8-diazabicylo [5,4,0] 11 carbon-7-alkene, 1,5-diazabicylo [4,3,0] ninth of the ten Heavenly Stems-5-alkene, N, two (trimethyl silicon based) ethanamides of O-, cesium carbonate, salt of wormwood, potassiumphosphate, Potassium ethanoate, potassiumphosphate, sodium hydride, n-Butyl Lithium, two (trimethyl silicon based) sodium amide, two (trimethyl silicon based) Lithamide, two (trimethyl silicon based) potassium amide, sodium methylate, proton sponge, potassium tert.-butoxide, sodium tert-butoxide or diisopropyl ethyl amine and alkali and three fluosulfonic acid silver, lithium chloride, the combination of the additives such as molecular sieve.
Described hexichol fluorosulfonyl methane compound, allyl carbonate ester compound, [Ir (COD) Cl]
2, part, alkali mol ratio be 1: 1-2: 0.01-0.1: 0.02-0.2: 0.05-3, the mol ratio of recommendation response is: hexichol fluorosulfonyl methane compound, allyl carbonate ester compound, [Ir (COD) Cl]
2, part, alkali mol ratio be 1: 1.1: 0.02-0.05: 0.04-0.1: 0.05-2.5.Reaction is 0 ℃ to 120 ℃ in temperature, and the recommendation response temperature is: 10 ℃ to 30 ℃.Reaction times is 3 hours-20 hours.
In the inventive method, described water is distilled water.Described organic solvent can be polarity or non-polar solvent.Such as benzene, tetracol phenixin, sherwood oil, tetrahydrofuran (THF), dimethyl formamide, ether, methylene dichloride, trichloromethane, toluene, dimethylbenzene, hexanaphthene, normal hexane, normal heptane, dioxane, acetonitrile etc.
Adopt the inventive method products therefrom 3-disulfonyl base fluoromethane replacement-1-propene compound can pass through recrystallization, thin-layer chromatography, the methods such as column chromatography underpressure distillation are separated.Such as the method with recrystallization, recommending solvent is the mixed solvent of polar solvent and non-polar solvent.Recommend solvent to can be methylene dichloride-normal hexane, Virahol-sherwood oil, ethyl acetate-sherwood oil, ethyl acetate-normal hexane, the Virahol-ethyl acetate-mixed solvents such as sherwood oil.With thin-layer chromatography and column chromatography method, used developping agent is the mixed solvent of polar solvent and non-polar solvent.Recommend solvent to can be Virahol-sherwood oil, ethyl acetate-sherwood oil, ethyl acetate-normal hexane, the Virahol-ethyl acetate-mixed solvents such as sherwood oil, its volume ratio can be respectively: polar solvent: non-polar solvent=1: 0.1-500.For example: ethyl acetate: sherwood oil=1: 0.1-50, Virahol: sherwood oil=1: 0.1-500.
The invention provides a kind of effectively by iridium complex as catalyzer, the method for synthesizing 3-disulfonyl base fluoromethane replacement-1-propene compound by disulfonyl base fluoromethanes and the high zone of allyl carbonate ester compound and high enantioselectivity ground; The method for preparing multiple 3-disulfonyl base fluoromethane replacement-1-propene compound is provided.The method is applicable to disulfonyl base fluoromethanes and the allyl carbonate ester compound of number of different types, and reaction conditions is gentle, and is easy and simple to handle.In addition, except alkali, need not to add any additive in the reaction.And the productive rate of reaction is better (being generally 28%-96%) also, and the regioselectivity height (be generally 84: 16-〉99: 1), enantioselectivity high (being generally 70%-96%).
The compound that contains the fluoromethane structure that removes synthetic aldehyde, alcohol, amine, carboxylic acid or polynary ring of the chemistry routes such as benzenesulfonyl, oxidation, two ammonification, cyclisation through reducing of synthesis of chiral 3-disulfonyl base fluoromethane replacement-1-propene compound of the present invention; this kind compound has special physiologically active, is medicine and the pesticide structure unit of commonly using.
Embodiment
To help to understand the present invention by following embodiment, but not limit content of the present invention.
Embodiment 1: the temperature of Fu Ke class allyl group alkylated reaction and the research of solvent occur in hexichol fluorosulfonyl band methane compound under iridium complex catalysis:
Wherein, mol refers to mole, and base refers to alkali, and solvent is solvent, and rt refers to room temperature.
Wherein, THF is tetrahydrofuran (THF), and toluene is toluene, and dioxane is dioxane, and DCE is dichloro hexane, and DCM is methylene dichloride, Et
2O is ether, and MeCN is acetonitrile, CDCl
3Be deuterochloroform, DBU is 1,8-diazabicylo [5,4,0], 11 carbon-7-alkene, and DABCO is Triethylene Diamine, and urotropine is urotropine; The amount of the used alkali of sequence number 1-10 is 1.1 times of consumptions, and sequence number 11-17 is 2.2 times of consumptions.
Embodiment 2: the research of different ligands hexichol fluorosulfonyl methane allyl group alkylated reaction under iridium complex catalysis:
1a R
3，R
4＝Ph
1d R
3，R
4＝Ph 1e R
5＝
iPr，Ar＝Ph
1b R
3，R
4＝2-Naphthyl
1c R
3，R
4＝2-MeO-Ph
Wherein Ph is phenyl, and Naphthyl is naphthyl, and MeO is methoxyl group,
iPr is sec.-propyl.
Embodiment 3: allyl group alkylated reaction occurs in hexichol fluorosulfonyl methane compound and allyl carbonate under the metal iridium complex catalysis
In the reaction tubes of a drying, add successively [Ir (COD) Cl]
2(0.004mmol), chiral ligand (0.008mmol), Tri N-Propyl Amine (0.5mL) and THF (0.5mL), then 50 ℃ of lower reactions 20 minutes naturally are chilled to the room temperature rear pump or output pump and drain.In reaction tubes, add hexichol fluorosulfonyl methane (0.2mmol), cesium carbonate (0.5mmol), allyl carbonate (0.22mmol), DCM (2mL) successively again, the stirring at room reaction.After reaction finished, the residue column chromatography for separation got product (ethyl acetate/petroleum ether=1/5-1/2, v/v) after the removal of solvent under reduced pressure.
P1:3-(the hexichol fluorosulfonyl is for methyl)-phenylpropyl alcohol-1-alkene
White solid, fusing point: 127-129 ℃; 89% productive rate, 94%ee; [chiral column OD-H (0.46cm * 25cm); Normal hexane/Virahol=98/2; Flow velocity=0.8mL/min; Detect wavelength=214nm; t
R=42.92 (minor), 46.55 (major) min].
[α]
D 20＝-39.4°(c 1.0，CHCl
3，＞99％ee).
1H NMR(400MHz，CDCl
3)δ＝7.86-7.84(m，2H)，7.67(t，J＝7.2Hz，1H)，7.55-7.45(m，5H)，7.31-7.15(m，7H)，6.86(ddd，J＝17.2，10.0，9.6Hz，1H)，5.46(d，J＝10.0Hz，1H)，5.31(d，J＝17.2Hz，1H)，4.62(dd，J＝13.6，9.6Hz，1H).
13C NMR(100MHz，CDCl
3)δ＝136.8(d，J＝3.7Hz)，135.9(d，J＝3.7Hz)，135.1，134.8，134.4，131.7，131.6，131.0(d，J＝2.3Hz)，130.5(d，J＝1.5Hz)，130.4(d，J＝1.5Hz)，128.7，128.4，128.1，127.8，121.5，116.2(d，J＝268.4Hz)，52.2(d，J＝17.1Hz).
19F NMR(282MHz，CDCl
3)δ＝-129.18(d，J＝12.7Hz).
MS (EI, m/z, rel.intensity) 77 (100); HRMS (EI) calculated value (calcd for) C
22H
19O
4FS
2(M
+): 430.0709, measured value (Found): 430.0706.
IR(KBr)：v
max(cm
-1)＝3095，2993，2910，1585，1496，1478，1450，1417，1349，1335，1291，1163，1147，1080，1071，1018，1004，970，936，761，746，697，688，682.
P2:3-(the hexichol fluorosulfonyl is for methyl)-to methoxyl group phenylpropyl alcohol-1-alkene
White solid, fusing point: 81-83 ℃; 95% yield, and 95%ee.[chiral column OD-H (0.46cm * 25cm); Normal hexane/Virahol=95/5; Flow velocity=0.7mL/min; Detect wavelength=214nm; t
R=38.38 (minor), 41.79 (major) min].
[α]
D 20＝-43.2°(c 1.0，CHCl
3).
1H NMR(400MHz，CDCl
3)δ＝7.85-7.83(m，2H)，7.68-7.64(m，1H)，7.54-7.46(m，5H)，7.30(dt，J＝7.6，1.6Hz，2H)，7.13(d，J＝7.6Hz，2H)，6.83(ddd，J＝16.8，10.0，9.2Hz，1H)，6.67(dt，J＝9.6，2.8Hz，2H)，5.43(d，J＝10.0Hz，1H)，5.28(d，J＝16.8Hz，1H)，4.58(dd，J＝13.6，9.2Hz，1H)，3.74(s，1H).
13C NMR(100MHz，CDCl
3)δ＝159.1，136.8，136.0，134.7，134.3，131.9，131.8，131.6，130.9(d，J＝2.2Hz)，130.35(d，J＝1.5Hz)，128.6，128.3，126.8，121.1，116.2(d，J＝268.5Hz)，113.4，55.1，51.4(d，J＝17.8Hz).
19F NMR(376MHz，CDCl
3)δ＝-128.02(d，J＝13.5Hz).
MS(EI，m/z，rel.intensity)460(M
+，1.6)，147(100)；HRMS(EI)calcd forC
23H
21O
5FS
2(M
+)：460.0814，Found：460.0812.
IR(KBr)：v
max(cm
-1)＝3068，2839，1610，1583，1513，1449，1344，1314，1255，1182，1163，1153，1079，1033，1000，913，831，755，734，685.
P3:3-(the hexichol fluorosulfonyl is for methyl)-meta-methoxy phenylpropyl alcohol-1-alkene
Colourless liquid, 91% yield, 91%ee.[chiral column OD-H (0.46cm * 25cm); Normal hexane/Virahol=90/10; Flow velocity=1.0mL/min; Detect wavelength=214nm; t
R=17.82 (minor), 19.49 (major) min].
[α]
D 20＝-9.5°(c 0.5，CHCl
3).
1H NMR(300MHz，CDCl
3)δ＝7.86(d，J＝7.8Hz，2H)，7.68(t，J＝7.5Hz，1H)，7.56-7.47(m，5H)，7.32(t，J＝7.5Hz，2H)，7.07(t，J＝7.5Hz，1H)，6.88-6.70(m，4H)，5.47(d，J＝10.8Hz，1H)，5.33(d，J＝16.8Hz，1H)，4.61(dd，J＝13.8，9.3Hz，1H)，3.69(s，3H).
13C NMR(75MHz，CDCl
3)δ＝158.9，136.7，136.3，135.8，135.6，135.14，135.07，134.7，134.3，131.4，131.3，130.84，130.83.130.76，130.2，130.0，129.3，128.9，128.5，128.2，122.7，121.4，116.0(d，J＝269.6Hz)，115.9，113.3，54.9，51.9(d，J＝17.2Hz).
19F NMR(282MHz，CDCl
3)δ＝-129.82(d，J＝13.3Hz).
MS(EI，m/z，rel.intensity)460(M
+，6.3)，77(100)；HRMS(EI)calcd forC
23H
21O
5FS
2(M
+)：460.0814，Found：460.0816.
IR(KBr)：v
max(cm
-1)＝3069，2838，2258，1601，1585，1492，1466，1449，1418，1348，1315，1291，1264，1157，1079，1050，1000，912，782，754，733，685.
P4:3-(the hexichol fluorosulfonyl is for methyl)-O-methoxy phenylpropyl alcohol-1-alkene
White powder, fusing point: 93-96 ℃; 86% yield, and 70%ee.[chiral column OD-H (0.46cm * 25cm); Normal hexane/Virahol=90/10; Flow velocity=1.0mL/min; Detect wavelength=214nm; t
R=21.58 (major), 27.90 (minor) min].
[α]
D 20＝-10.1°(c 0.5，CHCl
3).
1H NMR(400MHz，CDCl
3)δ＝7.86-7.84(m，2H)，7.77-7.75(m，2H)，7.65-7.59(m，3H)，7.47-7.42(m，4H)，7.18-7.14(m，1H)，6.89-6.74(m，2H)，6.65(dd，J＝1.2，8.4Hz，1H)，5.31(dd，J＝12.0，2.0Hz，1H)，5.19(d，J＝17.2Hz，1H)，5.13(dd，J＝10.4，8.8Hz，1H)，3.42(s，3H).
13C NMR(100MHz，CDCl
3)δ＝157.1，137.2，136.0，134.6，132.28，132.24，131.8，130.9，130.8，130.7，128.9，128.6，128.3，123.61，123.58，120.2，119.8，116.5(d，J＝217.9Hz)，110.2，55.2，44.3(d，J＝18.6Hz).
19F NMR(376MHz，CDCl
3)δ＝-133.03(d，J＝7.90Hz).
MS(EI，m/z，rel.intensity)147(100)；HRMS(EI)calcd for C
23H
21O
5FS
2(M
+)：460.0814，Found：460.0817.
IR(KBr)：v
max(cm
-1)＝3067，2841，1600，1585，1493，1464，1449，1349，1314，1291，1267，1250，1168，1153，1080，1029，999，931，738，704，686.
P5:3-(the hexichol fluorosulfonyl is for methyl)-to methyl phenylpropyl alcohol-1-alkene
White powder, fusing point: 84-87 ℃; 94% yield, and 94%ee.[chiral column AD-H (0.46cm * 25cm); Normal hexane/Virahol=90/10; Flow velocity=1.0mL/min; Detect wavelength=214nm; t
R=17.71 (major), 19.07 (minor) min].
[α]
D 20＝-73.5°(c1.0，CHCl
3).
1H NMR(300MHz，CDCl
3)δ＝7.84(d，J＝7.2Hz，2H)，7.69-7.64(m，1H)，7.55-7.45(m，5H)，7.28(t，J＝7.5Hz，2H)，7.10(d，J＝8.1Hz，2H)，6.95-6.78(m，3H)，5.44(d，J＝10.2Hz，1H)，5.29(d，J＝17.1Hz，1H)，4.59(dd，J＝13.8，9.3Hz，1H)，2.26(s，3H).
13C NMR(75MHz，CDCl
3)δ＝137.6，136.7，135.9，134.7，134.3，132.0，131.81，131.73，130.89，130.87，130.3，128.9，128.7，128.6，128.3，126.3，121.2，116.2(d，J＝268.5Hz)，51.8(d，J＝17.8Hz)，20.9.
19F NMR(282MHz，CDCl
3)δ＝-129.50(d，J＝13.25Hz).
MS(EI，m/z，rel.intensity)131(100)；HRMS(EI)calcd for C
23H
21O
4FS
2(M
+)：444.0865，Found：444.0867.
IR(KBr)：v
max(cm
-1)＝1584，1512，1448，1346，1336，1314，1162，1147，1079，1020，1000，930，809，764，753，714，689，682.
P6:3-(the hexichol fluorosulfonyl is for methyl)-to isobutyl-phenylpropyl alcohol-1-alkene
White solid, fusing point: 129-131 ℃; 96% yield, and 95%ee.[chiral column AD-H (0.46cm * 25cm); Normal hexane/Virahol=98/2; Flow velocity=1.0mL/min; Detect wavelength=254nm; t
R=51.54 (major), 57.80 (minor) min].
(S) configuration product: [α]
D 20=-41.6 ° (c 1.0, CHCl
3); (R) configuration product: [α]
D 20=+42.7 ° of (c1.10, CHCl
3, 94%ee).
1H NMR(400MHz，CDCl
3)δ＝7.87(d，J＝7.6Hz，2H)，7.67(t，J＝6.8Hz，1H)，7.50-7.43(m，5H)，7.27(t，J＝7.2Hz，2H)，7.12(d，J＝7.2Hz，2H)，6.93-6.82(m，3H)，5.45(d，J＝10.0Hz，1H)，5.31(d，J＝16.8Hz，1H)，4.61(dd，J＝12.4，10.0Hz，1H)，2.38(d，J＝6.8Hz，2H)，1.84-1.77(m，1H)，0.88(d，J＝6.8Hz，6H).
13C NMR(100MHz，CDCl
3)δ＝141.3，136.8，136.0，134.7，134.3，132.2，131.69，131.63，131.0，130.2，128.8，128.6，128.3，121.3，116.3(d，J＝268.4Hz)，51.8(d，J＝17.9Hz)，44.9，30.0，22.4.
19F NMR(376MHz，CDCl
3)δ＝-128.09(d，J＝11.3Hz).
MS(EI，m/z，rel.intensity)344(100)；HRMS(EI)calcd for C
26H
26O
4FS
2(M
+)：485.1257，Found：485.1250.
IR(KBr)：v
max(cm
-1)＝2952，2868，1584，1512，1478，1466，1449，1347，1337，1314，1164，1149，1079，1021，999，939，914，801，755，723，685.
P7:3-(the hexichol fluorosulfonyl is for methyl)-m-chloro phenylpropyl alcohol-1-alkene
White solid, fusing point: 109-113 ℃; 41% yield, and 94%ee.[chiral column AD-H (0.46cm * 25cm); Normal hexane/Virahol=98/2; Flow velocity=0.8mL/min; Detect wavelength=214nm; t
R=80.38 (major), 84.06 (minor) min].
[α]
D 20＝-14.5°(c 0.5，CHCl
3).
1H NMR(300MHz，CDCl
3)δ＝7.87(d，J＝7.2Hz，2H)，7.69(t，J＝7.2Hz，1H)，7.57-7.48(m，5H)，7.32(t，J＝7.5Hz，2H)，7.17-7.09(m，4H)，6.80(ddd，J＝17.1，9.6，7.5Hz，1H)，5.50(d，J＝10.2Hz，1H)，5.33(d，J＝16.8Hz，1H)，4.61(dd，J＝13.5，9.3Hz，1H).
13C NMR(75MHz，CDCl
3)δ＝137.1，136.5，135.8，135.0，134.6，133.8，131.02，130.99，130.89，130.80，130.45，130.30，130.28，129.2，128.4，128.0，122.2，115.7(d，J＝269.1Hz)，51.6(d，J＝17.2Hz).
19F NMR(282MHz，CDCl
3)δ＝-129.89(d，J＝13.3Hz).
MS(EI，m/z，rel.intensity)77(100)；HRMS(EI)calcd for C
22H
19O
4FClS
2(MH
+)：465.0397，Found：465.0390.
IR(KBr)：v
max(cm
-1)＝2918，1596，1573，1475，1447，1433，1347，1310，1289，1160，1146，1078，999，968，950，872，844，784，753，707，683.
P8:3-(the hexichol fluorosulfonyl is for methyl)-to bromobenzene third-1-alkene
White solid, fusing point: 163-165 ℃; 66% yield, 92%ee (can get behind the recrystallization 54% yield and＞99%ee) .[chiral column IC (0.46cm * 25cm); Normal hexane/Virahol=80/20; Flow velocity=0.8mL/min; Detect wavelength=214nm; t
R=35.98 (major), 60.54 (minor) min].
[α]
D 20＝-44.1°(c 1.0，CHCl
3，＞99％ee).
1H NMR(300MHz，CDCl
3)δ＝7.84(d，J＝7.8Hz，2H)，7.69(t，J＝7.2Hz，1H)，7.59-7.46(m，5H)，7.35-7.24(m，4H)，7.09(d，J＝8.1Hz，1H)，6.81(ddd，J＝17.1，9.6，7.5Hz，1H)，5.47(d，J＝9.9Hz，1H)，5.31(d，J＝17.1Hz，1H)，4.59(dd，J＝13.2，9.3Hz，1H).
13C NMR(75MHz，CDCl
3)δ＝136.4，135.7，134.9，134.5，134.2，132.1，131.10，131.01，130.93，130.2，128.7，128.5，122.2，121.9，115.8(d，J＝268.5Hz)，51.5(d，J＝17.2Hz).
19F NMR(282MHz，CDCl
3)δ＝-129.69(d，J＝13.3Hz).
MS(EI，m/z，rel.intensity)77(100)；HRMS(EI)calcd for C
22H
18O
4FBrS
2(M
+)：507.9814，Found：507.9812.IR(KBr)：v
max(cm
-1)＝2923，2852，1583，1488，1448，1314，1162，1147，1079，1011，937，815，716，684.
P9:3-(the hexichol fluorosulfonyl is for methyl)-to trifluoromethyl phenylpropyl alcohol-1-alkene
White solid, fusing point: 127-129 ℃; 60% yield, and 91%ee.[chiral column AD-H (0.46cm * 25cm); Normal hexane/Virahol=90/10; Flow velocity=1.0mL/min; Detect wavelength=214nm; t
R=17.50 (minor), 20.80 (major) min].
[α]
D 20＝-35.2°(c 0.5，CHCl
3).
1H NMR(400MHz，CDCl
3)δ＝7.85(d，J＝8.4Hz，2H)，7.69(t，J＝7.6Hz，1H)，7.56-7.46(m，5H)，7.41-7.28(m，6H)，6.84(ddd，J＝17.2，10.0，7.2Hz，1H)，5.50(d，J＝10.0Hz，1H)，5.33(d，J＝16.8Hz，1H)，4.70(dd，J＝13.6，9.2Hz，1H).
13C NMR(100MHz，CDCl
3)δ＝139.4，136.5，135.8，135.0，134.7，131.02，131.00，130.90，130.88，130.30，130.30，128.8，128.5，124.9(q，J＝3.7Hz)，122.3，115.8(d，J＝269.2Hz)，51.8(d，J＝17.1Hz).
19F NMR(376MHz，CDCl
3)δ＝-62.76(s，3F)，-129.66(d，J＝13.2Hz，1F).
MS(EI，m/z，rel.intensity)77(100)；HRMS(EI)calcd for C
23H
18O
4F
4S
2(M
+)：498.0583，Found：498.0585.
IR(KBr)：v
max(cm
-1)＝2918，2852，1618，1583，1448，1426，1412，1348，1332，1293，1162，1147，1117，1073，1020，951，832，819，756，745，723，707，684.
P10:3-(the hexichol fluorosulfonyl is for methyl)-3-(6-methoxyl group-2-naphthyl)-1-propylene
White solid, fusing point: 131-133 ℃; 89% yield, and 93%ee.[chiral column AD-H (0.46cm * 25cm); Normal hexane/Virahol=90/10; Flow velocity=1.0mL/min; Detect wavelength=254nm; t
R=26.76 (minor), 29.67 (major) min].
[α]
D 20＝-73.9°(c 1.0，CHCl
3).
1H NMR(400MHz，CDCl
3)δ＝7.85(d，J＝8.4Hz，2H)，7.63-7.54(m，3H)，7.45-7.34(m，6H)，7.26(d，J＝8.4Hz，1H)，7.11-7.07(m，3H)，7.01(s，1H)，6.94(ddd，J＝16.8，10.0，6.8Hz，1H)，5.50(d，J＝10.0Hz，1H)，5.36(d，J＝16.8Hz，1H)，4.79(dd，J＝14.8，9.2Hz，1H)，3.90(s，3H).
13C NMR(100MHz，CDCl
3)δ＝158.0，136.8，136.2，134.6，134.1，133.9，131.75，131.69，131.0，130.19，130.10，129.7，129.5，128.52，128.39，128.38，128.1，126.4，121.5，118.9，116.5(d，J＝268.5Hz)，105.2，55.3，51.9(d，J＝17.1Hz).
19F NMR(376MHz，CDCl
3)δ＝-129.81(d，J＝14.7Hz).
MS(EI，m/z，rel.intensity)510(M
+，10.8)，197(100)；HRMS(EI)calcd forC
27H
23O
5FS
2(M
+)：510.0971，Found：510.0975.
IR(KBr)：v
max(cm
-1)＝3071，1632，1599，1582，1506，1483，1447，1411，1396，1345，1314，1264，1227，1170，1160，1150，1078，1027，1010，965，905，853，812，761，753，687.
P11:3-(the hexichol fluorosulfonyl is for methyl)-3-(2-thiophene)-1-propylene
Yellow oily liquid, 28% yield, 96%ee.[chiral column AD-H (0.46cm * 25cm); Normal hexane/Virahol=90/10; Flow velocity=1.0mL/min; Detect wavelength=254nm; t
R=20.43 (major), 21.64 (minor) min].
[α]
D 20＝+13.3°(c 0.5，CHCl
3).
1H NMR(300MHz，CDCl
3)δ＝7.97(d，J＝7.8Hz，2H)，7.72(t，J＝7.2Hz，1H)，7.58-7.48(m，3H)，7.42(d，J＝7.8Hz，2H)，7.30(d，J＝7.5Hz，2H)，7.11(d，J＝5.1Hz，1H)，6.89(d，J＝2.4Hz，1H)，6.88-6.76(m，2H)，5.56(d，J＝10.2Hz，1H)，5.46(d，J＝16.8Hz，1H)，4.92(t，J＝10.5Hz，1H).
13C NMR(100MHz，CDCl
3)δ＝136.7，136.6，136.0，134.9，134.3，131.31，131.28，131.24，130.7，130.6，130.10，130.08，128.99，128.70，128.68，128.63，128.4，126.5，122.8，115.1(d，J＝267.7Hz)，47.9(d，J＝17.9Hz).
19F NMR(282MHz，CDCl
3)δ＝-126.97(d，J＝12.1Hz).
MS(EI，m/z，rel.intensity)123(100)；HRMS(EI)calcd for C
20H
17O
4FS
3(M
+)：436.0273，Found：436.0276.
IR(KBr)：v
max(cm
-1)＝3071，2925，1638，1584，1478，1449，1418，1347，1315，1181，1168，1154，1079，999，937，912，755，734，708，685.
P12:3-(the hexichol fluorosulfonyl is for methyl)-Isosorbide-5-Nitrae-hexadiene
Colourless oil liquid, 52% yield, 75%ee.[chiral column OD-H (0.46cm * 25cm); Normal hexane/Virahol=95/5; Flow velocity=0.7mL/min; Detect wavelength=230nm; t
R=26.34 (minor), 28.29 (major) min].
[α]
D 20＝+13.7°(c 0.5，CHCl
3).
1H NMR(300MHz，CDCl
3)δ＝7.92-7.83(m，4H)，7.72-7.66(m，2H)，7.58-7.49(m，4H)，6.19(ddd，J＝17.1，10.2，7.2Hz，1H)，5.66-5.46(m，2H)，5.24(dd，J＝10.2，1.2Hz，1H)，5.13(d，J＝16.8Hz，1H)，3.88(dd，J＝13.8，6.9Hz，1H)，1.65(d，J＝5.7Hz，3H).
13C NMR(75MHz，CDCl
3)δ＝136.7，136.2，136.0，135.22，135.18，134.99，134.94，132.0，131.66，131.59，130.98，130.91，130.89，130.4，128.9，128.8，128.7，123.47，123.40，119.9，117.97，117.88，114.9(d，J＝266.2Hz)，50.5(d，J＝18.3Hz)，18.0.
19F NMR(282MHz，CDCl
3)δ＝-130.87(d，J＝7.6Hz).
MS(EI，m/z，rel.intensity)77(100)；HRMS(EI)calcd for C
19H
19O
4FS
2(M
+)：394.0709，Found：394.0703.
IR(KBr)：v
max(cm
-1)＝3068，2918，2856，1637，1584，1478，1449，1418，1348，1315，1293，1165，1154，1080，998，971，930，847，755，728，686.
P13:3-(the hexichol fluorosulfonyl is for methyl)-1-butylene
Colourless oil liquid, 92% yield, 89%ee.[chiral column IC (0.46cm * 25cm); Normal hexane/Virahol=80/20; Flow velocity=0.7mL/min; Detect wavelength=214nm; t
R=24.43 (major), 25.93 (minor) min].
[α]
D 20＝+18.1°(c 1.0，CHCl
3).
1H NMR(400MHz，CDCl
3)δ＝7.88-7.84(m，4H)，7.71-7.65(m，2H)，7.53-7.47(m，4H)，6.09(ddd，J＝17.6，10.4，3.6Hz，1H)，5.12(d，J＝10.4Hz，1H)，5.01(d，J＝17.2Hz，1H)，3.34-3.25(m，1H)，1.57(dd，J＝7.2，1.2Hz，3H).
13C NMR(100MHz，CDCl
3)δ＝136.2，135.7，135.2，135.1，135.0，134.9，134.0，133.9，130.81，130.79，130.76，128.94，128.86，128.81，128.7，118.7，117.2，114.6，42.1(d，J＝17.8Hz)，14.5(d，J＝5.6Hz).
19F NMR(376MHz，CDCl
3)δ＝-130.81.
MS(EI，m/z，rel.intensity)77(100)；HRMS(EI)calcd for C
17H
17O
4FS
2(M
+)：368.0552，Found：368.0546.
IR(KBr)：v
max(cm
-1)＝3069，2950，1639，1584，1478，1449，1419，1347，1315，1292，1163，1153，1079，1046，999，931，842，755，726，685.
P14:3-(the dibenzyl fluorosulfonyl is for methyl)-phenylallene
R＝Bn
White powder, fusing point: 93-97 ℃; 42% yield, and 90%ee.[chiral column AD-H (0.46cm * 25cm); Normal hexane/Virahol=90/10; Flow velocity=1.0mL/min; Detect wavelength=214nm; t
R=34.22 (minor), 50.27 (major) min].
[α]
D 20＝-50.3°(c 0.5，CHCl
3).
1H NMR(300MHz，CDCl
3)δ＝8.42-8.39(m，1H)，8.12(d，J＝7.5Hz，1H)，8.06(d，J＝8.1Hz，1H)，7.93-7.72(m，5H)，7.49(t，J＝7.5Hz，1H)，7.423-7.35(m，3H)，7.25-7.21(m，3H)，7.15-7.02(m，4H)，6.93(ddd，J＝17.1，9.9，7.2Hz，1H)，5.46(d，J＝10.2Hz，1H)，5.33(d，J＝17.1Hz，1H)，4.82(dd，J＝16.2，9.3Hz，1H).
13C NMR(75MHz，CDCl
3)δ＝136.5，136.2，135.6，134.8，133.7，133.5，133.0，132.1，132.0，131.9，130.68，130.65，130.3，130.15，130.12，128.54，128.49，128.42，127.99，127.93，127.8，126.8，126.6，125.4，125.3，124.9，124.8，124.0，123.0，121.0，118.4(d，J＝273.1Hz)，52.4(d，J＝16.7Hz).
19F NMR(282MHz，CDCl
3)δ＝-131.23(br).
MS(ESI，m/z，rel.intensity)553(MNa
+)；HRMS(EI)calcd for C
30H
23O
4FS
2Na(MNa
+)：553.0926，Found：553.0914.
IR(KBr)：v
max(cm
-1)＝3060，2924，1593，1565，1506，1453，1337，1198，1164，1129，1028，970，932，828，806，768，697，672.
P15:3-(the hexichol fluorosulfonyl is for methyl)-m-phenoxy phenylallene
Yield: 91%; Ee%:95%; MS (ESI, m/z, rel.intensity) 545 (MNa
+).
P16:3-(the hexichol fluorosulfonyl is for methyl)-fluorine is to the phenyl phenylallene
Yield: 84%; Ee%:92%; MS (ESI, m/z, rel.intensity) 547 (MNa
+).
P17:3-(the hexichol fluorosulfonyl is for methyl)-to (N-indoline-1 '-ketone) phenylallene
[(S)-2-(4-(1-fluoro-1，1-bis(phenylsulfonyl)but-3-en-2-yl)phenyl)isoindolin-1-one]
Yield: 81%; Ee%:93%; MS (ESI, m/z, rel.intensity) 584 (MNa
+).
P18:3-(the hexichol fluorosulfonyl is for methyl)-benzoyl phenylallene
[(3-(1-fluoro-1，1-bis(phenylsulfonyl)but-3-en-2-yl)phenyl)(phenyl)methanone]
Yield: 84%; Ee%:92%; MS (ESI, m/z, rel.intensity) 557 (MNa
+).
P19:3-(the hexichol fluorosulfonyl is for methyl)-to [(2 '-cyclopentanone base) methyl] phenylallene
[2-(4-((S)-1-fluoro-1，1-bis(phenylsulfonyl)but-3-en-2-yl)benzyl)cyclopentanone]
Yield: 87%; Ee%:94%; MS (ESI, m/z, rel.intensity) 549 (MNa
+).
P20:3-(the hexichol fluorosulfonyl is for methyl)-to [(2 '-thienyl) formyl radical] phenylallene
[(S)-(4-(1-fluoro-1，1-bis(phenylsulfonyl)but-3-en-2-yl)phenyl)(thiophen-2-yl)methanone]
Yield: 84%; Ee%:96%; MS (ESI, m/z, rel.intensity) 563 (MNa
+).
P21:3-(the hexichol fluorosulfonyl is for methyl)-{ (10 '-ketone-10 ', 11 '-dihydrobenzo [b, f] thiazinyl)-2 ' }-propylene
[(S)-2-(1-fluoro-1，1-bis(phenylsulfonyl)but-3-en-2-yl)dibenzo[b，f]thiepin-10(11H)-one]
Yield: 80%; Ee%:91%; MS (ESI, m/z, rel.intensity) 601 (MNa
+).
P22:5-(1 '-fluoro-, 1 ', 1 '-two benzenesulfonyls-3 '-butene-2 ')-(2-(to fluorophenyl) benzo [d] oxazole
[(S)-5-(1-fluoro-1，1-bis(phenylsulfonyl)but-3-en-2-yl)-2-(4-fluorophenyl)benzo[d]oxazole]
Yield: 83%; Ee%:92%; MS (ESI, m/z, rel.intensity) 588 (MNa
+).
P23:3-(the hexichol fluorosulfonyl is for methyl)-(p-N-(2 ', 5 '-pyrrolin)-m-chloro) phenylallene
[(S)-1-(2-chloro-4-(1-fluoro-1，1-bis(phenylsulfonyl)but-3-en-2-yl)phenyl)-2，5-dihydro-1H-pyrrole]
Yield: 87%; Ee%:94%; MS (ESI, m/z, rel.intensity) 554 (MNa
+).
P23:6-chloro-2-(1 '-fluoro-, 1 ', 1 '-two benzenesulfonyls-3 '-butene-2 '-)-the 9H-carbazole
[(S)-6-chloro-2-(1-fluoro-1，1-bis(phenylsulfonyl)but-3-en-2-yl)-9H-carbazole]
Yield: 89%; Ee%:92%; MS (ESI, m/z, rel.intensity) 576 (MNa
+).
Embodiment 4: the chemical conversion of chirality 3-hexichol fluorosulfonyl methane-1-propene compound
(R) (R)
ee：94％ ee：95％
Under argon shield; in the round-bottomed flask of a drying, add 3-(the hexichol fluorosulfonyl is for methyl)-to isobutyl-benzene propylene (95%ee, 243.1mg, 0.50mmol) and the activation magnesium chips (360.8mg; 15.0mmol), add again MeOH (5.0mL).After the stirring at room 12 hours, add saturated aqueous ammonium chloride, with anhydrous diethyl ether extraction (4 * 8mL), after merging organic phase, with the saturated common salt washing once, anhydrous magnesium sulfate drying, removal of solvent under reduced pressure, the silica gel column chromatography colourless liquid (ether/normal hexane=1/10) of purifying to get.
P24:3-fluoro methyl-to the isobutyl-benzene propylene
91% yield, and 95%ee[chiral column OJ-H (0.46cm * 25cm); Normal hexane/Virahol=1000/1; Flow velocity=0.8mL/min; Detect wavelength=214nm; t
R=10.32 (major), 11.37 (minor) min]. (R) configuration product: [α]
D 20=-41.2 ° of (c=1.0, CHCl
3); (S) configuration product: [α]
D 20=+41.8 ° of (c=1.3, CHCl
3, 95%ee).
1H NMR(400MHz，CDCl
3)δ＝7.19(d，J＝8.4Hz，2H)，7.16(d，J＝8.4Hz，2H)，6.08(ddd，J＝17.2，10.4，6.8Hz，1H)，5.26(d，J＝10.4Hz，1H)，5.23(d，J＝16.8Hz，1H)，4.65(dd，J＝47.2，6.8Hz，2H)，3.75(dt，J＝23.6，6.8Hz，1H)，2.51(d，J＝7.6Hz，2H)，1.97-1.84(m，1H)，0.96(d，J＝6.4Hz，6H).
13C NMR(100MHz，CDCl
3)δ＝140.5，137.1(d，J＝5.2Hz)，136.5(d，J＝6.0Hz)，129.4，127.7，116.9，85.6(d，J＝174.0Hz)，49.6(d，J＝19.3Hz)，45.0，30.2，22.4.
19F NMR(376MHz，CDCl
3)δ＝-216.96(dt，J＝47.7，16.9Hz).
MS(EI，m/z，rel.intensity)117(100)，206(M
+，57)；HRMS(EI)calcd forC
14H
19F(M
+)：206.1471，Found：206.1476.
IR(KBr)：v
max(cm
-1)＝3086，2957，2926，2870，1640，1514，1467，1420，1384，1367，1261，1168，1116，1016，996，921，845，795.
P25:3-fluoro methyl-(6-methoxyl group-2-naphthyl)-propylene
Embodiment 5: the chemical conversion of chirality 3-methyl fuoride-1-propene compound
(R)-5af (S)-6af
In a round-bottomed flask, (R)-5af (95%ee, 41.7mg, 0.2mmol) and NaIO
4(213.8mg, 1.0mmol) adds RuCl after being dissolved in the mixed solvent of the tetracol phenixin of 2mL and acetonitrile (1: 1) again
3(H
2O) aqueous solution of (2.1mg, 0.01mmol) (1.5mL), stirring at room 1.5 hours adds ether (5mL) and saturated sodium bicarbonate aqueous solution (5mL).With sodium bicarbonate aqueous solution extraction (5mL * 5), merge water, after 0 degree centigrade of lower slowly adding concentrated hydrochloric acid adjust pH is 1, with dichloromethane extraction (5mL * 4), merge organic phase, anhydrous Na
2SO
4Drying, removal of solvent under reduced pressure obtains target product (S)-6af.
P26: chirality fluoro Ibuprofen BP/EP
White solid, 91% yield,
(S) product of configuration: [α]
D 20=+53.9 ° (c=0.9, EtOH);
(R) product of configuration: [α]
D 20=-54.5 ° (c=1.0, EtOH).
1H NMR(400MHz，CDCl
3)δ＝11.11(br s，1H)，7.21(d，J＝8.0Hz，2H)，7.12(d，J＝8.4Hz，2H)，4.93(dt，J＝46.8，9.2Hz，1H)，4.57(ddd，J＝46.8，9.2，5.2Hz，1H)，4.01(ddd，J＝17.6，9.2，5.2Hz，1H)，2.45(d，J＝7.2Hz，2H)，1.89-1.79(m，1H)，0.89(d，J＝7.2Hz，6H).
13C NMR(100MHz，CDCl
3)δ＝177.7，142.1，130.2(d，J＝8.2Hz)，129.8，127.9，84.3(d，J＝173.3Hz)，51.7(d，J＝20.9Hz)，45.0，30.1，22.3.
19F NMR(376MHz，CDCl
3)δ＝-221.97(dt，J＝46.2，13.2Hz).
MS(EI，m/z，rel.intensity)117(100)，224(M
+，32)；HRMS(EI)calcd forC
13H
17FO
2(M
+)：224.1213，Found：224.1206.
IR(KBr)：v
max(cm
-1)＝2963，1732，1699，1514，1465，1423，1368，1263，1226，1167，1100，1011，801.
P27: fluoro Naproxen Base
Claims (8)
1. 3-disulfonyl base fluoromethane replacement-1-propene compound, it has the optical pure compound of following structural formula:
Wherein * is chiral carbon atom, R
1Be selected from arbitrarily C
1-C
16Alkyl, C
3-C
16Cycloalkyl, C
4-C
10The heterocyclic radical that contains N, O or S or the aryl that replaces of R; R is C
1-C
4Alkyl, C
1-C
4Perfluoroalkyl, halogen or C
1-C
4Alkoxyl group; R
2Be aryl; Described aryl is phenyl or naphthyl.
2. the synthetic method of a 3-disulfonyl base fluoromethane replacement-1-propene compound as claimed in claim 1; it is characterized in that in organic solvent; under-20 ℃～120 ℃, take allyl carbonate ester compound and disulfonyl base fluoromethanes as raw material, with [Ir (COD) Cl]
2The iridium complex that generates with the part effect is as catalyzer, and reaction made 3-disulfonyl base fluoromethane replacement-1-propene compound in 5-48 hour under the effect of alkali;
Above-mentioned disulfonyl base fluoromethanes, allyl carbonate ester compound, [Ir (COD) Cl]
2, part, alkali mol ratio be 1: 1-2: 0.01-0.1: 0.02-0.2: 0.05-3;
Described allyl carbonate ester compound structural formula is:
Disulfonyl base fluoromethanes structural formula is:
Described part is the optically pure part with following structural formula:
Described alkali is triethylamine, 1,8-diazabicylo [5,4,0] 11 carbon-7-alkene, 1,5-diazabicylo [4,3,0] ninth of the ten Heavenly Stems-5-alkene, triethylene diamine, N, two (trimethyl silicon based) ethanamides of O-, cesium carbonate, salt of wormwood, potassiumphosphate, Potassium ethanoate, sodium hydride, n-Butyl Lithium, two (trimethyl silicon based) sodium amide, two (trimethyl silicon based) Lithamide, two (trimethyl silicon based) potassium amide, sodium methylate, proton sponge, potassium tert.-butoxide, sodium tert-butoxide or diisopropyl ethyl amine; The perhaps combination of alkali and three fluosulfonic acid silver, lithium chloride or molecular sieve additive;
R wherein
1, R
2As claimed in claim 1;
R
3, R
4Perhaps R
5Be selected from arbitrarily C
3-C
16Cycloalkyl, phenyl, naphthyl, C
1-C
4The alkoxyl group phenyl or the C that replace
1-C
4The alkyl of the alkoxyl group naphthyl, sec.-propyl or the tertiary butyl that replace; LG is leavings group, is methyl carbonate, ethyl ester, tertiary butyl ester.
3. the method for synthetic 3-disulfonyl base fluoromethane replacement-1-propene compound as claimed in claim 2 is characterized in that described disulfonyl base fluoromethanes, allyl carbonate ester compound, [Ir (COD) Cl]
2, part, alkali mol ratio be 1: 1.1: 0.02-0.05: 0.04-0.1: 0.05-2.5.
4. the method for synthetic 3-disulfonyl base fluoromethane replacement-1-propene compound as claimed in claim 2 is characterized in that described organic solvent is benzene, tetracol phenixin, sherwood oil, tetrahydrofuran (THF), dimethyl formamide, ether, methylene dichloride, trichloromethane, toluene, dimethylbenzene, hexanaphthene, normal hexane, normal heptane, dioxane or acetonitrile.
5. the method for synthetic 3-disulfonyl base fluoromethane replacement-1-propene compound as claimed in claim 2 is characterized in that products therefrom is through the separation of recrystallization, thin-layer chromatography, column chromatography or underpressure distillation.
6. a 3-disulfonyl base fluoromethane replacement-1-propene compound purposes as claimed in claim 1 is characterized in that the pharmaceutical intermediate with special physiological function for the preparation of the carboxylic acid that contains the building block of single fluoro methyl.
7. purposes as claimed in claim 6 is characterized in that the described carboxylic acid that contains the building block of single fluoro methyl is the single methyl fuoride replacement-1-of the optical purity 2-carboxylic acid compound with following structural formula:
Wherein * is chiral carbon atom, R
1As claimed in claim 1.
8. purposes as claimed in claim 7, it is characterized in that in organic solvent, under-20 ℃～50 ℃, take 3-disulfonyl base fluoromethane replacement-1-propene compound as raw material, reaction made the single fluoromethane replacement-1-of 3-propene compound in 1.5-24 hour under the effect of buffer reagent and MAGNESIUM METAL or sodium amalgam; The single fluoromethane replacement-1-of the 3-that is synthesized propene compound is reoxidised into the method for the single methyl fuoride replacement-1-of 2-carboxylic acid compound under the effect of organic solvent and oxygenant;
Above-mentioned 3-disulfonyl base fluoromethane replacement-1-propene compound and the ratio of MAGNESIUM METAL or sodium amalgam are 1: 10-40;
The single fluoromethane replacement-1-of above-mentioned 3-propene compound structural formula is:
Wherein, R
1As claimed in claim 1; Described organic solvent is methyl alcohol, dimethyl formamide or acetic acid; Wherein buffer reagent is acetic acid/sodium-acetate or acetic acid/sodium hydrogen phosphate.
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| CN102786454A (en) * | 2011-05-20 | 2012-11-21 | 同济大学 | Bis[1-aryl(alkyl) substituted allyl]sulphane compound and synthetic method and application thereof |
| CN103896816B (en) * | 2012-12-26 | 2016-11-02 | 同济大学 | A kind of chirality allyl sulfhydrate carboxylate and synthetic method thereof |
| CN104193667B (en) * | 2014-08-01 | 2016-10-19 | 常州大学 | The synthetic method of the azacyclo-that a kind of divergence form guides |
| CN104530049B (en) * | 2014-12-09 | 2016-06-15 | 河南师范大学 | A kind of method synthesizing fluorine-containing acyclonucleosides analog |
| CN108373431A (en) * | 2018-02-08 | 2018-08-07 | 同济大学 | Fluorine-containing chirality allyl compound and its synthetic method |
| CN114853661A (en) * | 2022-05-18 | 2022-08-05 | 华东理工大学 | Fluoroamidoibuprofen derivative and preparation method and application thereof |
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