CN101565393A - 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, are widely 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 fluoromethane compounds 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 that contains aldehyde, aldehyde, alcohol, amine, carboxylic acid or the polynary ring of single fluoro methyl of chemistry routes such as alkylsulfonyl, oxidation, two ammonification, cyclisation with special physiological effect.
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 introducing single methyl fuoride in compound is the comparison difficulty.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.; Alconcl., 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 catalyzing by metal palladium is the asymmetric allylation of nucleophilic reagent with hexichol fluorosulfonyl methane, 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 two key reduction.In order to address this problem; we have invented catalytic by metal iridium is the allyl substitution reaction of nucleophilic reagent with disulfonyl base methyl fuoride; 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 methyl building block of disulfonyl base fluoro and terminal double link in this product simultaneously; be easy to generate compounds such as the acid that contains single fluoro methyl group unit, aldehyde, alcohol, amine, polynary ring, so this method there is very important meaning to synthetic this type of compound by simple derivatize.
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 C arbitrarily
1-C
16Alkyl, C
3-C
16Cycloalkyl, C
4-C
10Heterocyclic 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 C arbitrarily
1-C
16Alkyl, C
3-C
16Cycloalkyl, C
4-C
10Heterocyclic radical that contains N, O or S or C
4-C
10The heteroaryl that contains N, O or S, aryl;
Described aryl is a 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 synthetic chirality 3-of institute disulfonyl base fluoromethane replacement-1-propene compound of the present invention 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 to be raw material with hexichol fluorosulfonyl methane compound and allyl carbonate ester compound, in the presence of organic solvent, with [Ir (COD) Cl]
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 a chiral ligand, and Base is the combination of various alkali mentioned above and alkali and additive, and Solv. is an all kinds of SOLVENTS mentioned above, and LG is a leavings group, is methyl carbonate, ethyl ester, carbonic acid tertiary butyl ester or the like.
Allyl carbonate ester compound structural formula is:
Hexichol fluorosulfonyl methane compound structural formula is:
R wherein
1, R
2Be selected from C arbitrarily
1-C
16Alkyl, C
3-C
16Cycloalkyl, C
4-C
10Heterocyclic 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 a phenyl or naphthyl; R is C
1-C
4Alkyl, C
1-C
4Perfluoroalkyl, halogen or C
1-C
4Alkoxyl group; LG is a 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 C arbitrarily
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, the combination of additives such as 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, 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.Being reflected at temperature is 0 ℃ to 120 ℃, 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.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, methods such as column chromatography underpressure distillation are separated.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, 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, 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 fluoromethane compounds 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.This method is applicable to the disulfonyl base fluoromethane compounds and the allyl carbonate ester compound of number of different types, and the reaction conditions gentleness is easy and simple to handle.In addition, except that alkali, need not to add any additives 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 height (being generally 70%-96%).
The process reduction of synthesis of chiral 3-disulfonyl base fluoromethane replacement-1-propene compound of the present invention removes the compound that contains the fluoromethane structure of chemistry route synthetic aldehyde, alcohol, amine, carboxylic acid or polynary rings such as benzenesulfonyl, oxidation, two ammonification, cyclisation; this kind compound has special physiologically active, is medicine and the pesticide structure unit of using always.
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 take place in hexichol fluorosulfonyl band methane compound under iridium complex catalysis:
Wherein, mol refers to mole, and base refers to alkali, and solvent is a solvent, and rt is meant room temperature.
Wherein, THF is a tetrahydrofuran (THF), and toluene is a toluene, and dioxane is a dioxane, and DCE is a dichloro hexane, and DCM is a methylene dichloride, Et
2O is an ether, and MeCN is an acetonitrile, CDCl
3Be deuterochloroform, DBU is 1,8-diazabicylo [5,4,0] 11 carbon-7-alkene, and DABCO is a Triethylene Diamine, urotropine is a 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 a phenyl, and Naphthyl is a naphthyl, and MeO is a methoxyl group,
iPr is a sec.-propyl.
Embodiment 3: allyl group alkylated reaction takes place in hexichol fluorosulfonyl methane compound and allyl carbonate under the catalysis of metal iridium complex
In an exsiccant reaction tubes, add successively [Ir (COD) Cl]
2(0.004mmol), chiral ligand (0.008mmol), Tri N-Propyl Amine (0.5mL) and THF (0.5mL), 50 ℃ of reactions 20 minutes down are chilled to the room temperature rear pump or output pump then naturally and drain.In reaction tubes, add hexichol fluorosulfonyl methane (0.2mmol), cesium carbonate (0.5mmol), allyl carbonate (0.22mmol), DCM (2mL), stirring at room reaction more successively.After reaction finishes, after the removal of solvent under reduced pressure residue column chromatography for separation get product (ethyl acetate/petroleum ether=1/5-1/2, v/v).
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 (0.46cmx 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)：ν
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, 95%ee.[chiral column OD-H (0.46cm x25cm); 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)：ν
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 (0.46cmx25cm); 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)：ν
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, 70%ee.[chiral column OD-H (0.46cmx25cm); 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)：ν
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, 94%ee.[chiral column AD-H (0.46cmx25cm); 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°(c?1.0，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)：ν
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, 95%ee.[chiral column AD-H (0.46cmx25cm); 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)：ν
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, 94%ee.[chiral column AD-H (0.46cmx25cm); 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)：ν
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 (0.46cmx25cm); 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)：ν
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, 91%ee.[chiral column AD-H (0.46cmx25cm); 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)：ν
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, 93%ee.[chiral column AD-H (0.46cmx25cm); 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)：ν
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 (0.46cmx25cm); 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)：ν
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)-1, the 4-hexadiene
Colourless oil liquid, 52% yield, 75%ee.[chiral column OD-H (0.46cmx25cm); 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)：ν
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 (0.46cmx25cm); 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)：ν
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
White powder, fusing point: 93-97 ℃; 42% yield, 90%ee.[chiral column AD-H (0.46cmx25cm); 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)：ν
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) be methanone (phenyl)]
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)-and 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)-and 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)-(right-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
Under argon shield, add in an exsiccant round-bottomed flask that 3-(the hexichol fluorosulfonyl is for methyl)-(0.50mmol) (360.8mg 15.0mmol), adds MeOH (5.0mL) again with the activatory magnesium chips for 95%ee, 243.1mg to the isobutyl-benzene propylene.After the stirring at room 12 hours, add saturated aqueous ammonium chloride, with anhydrous diethyl ether extraction (4x8mL), after merging organic phase, with the saturated common salt washing once, anhydrous magnesium sulfate drying, removal of solvent under reduced pressure, silica gel column chromatography purify colourless liquid (ether/normal hexane=1/10).
P24:3-fluoro methyl-to the isobutyl-benzene propylene
91% yield, 95%ee[chiral column OJ-H (0.46cmx25cm); 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)：ν
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
In a round-bottomed flask, (R)-5af (95%ee, 41.7mg, 0.2mmol) and NaIO
4(213.8mg, 1.0mmol) be dissolved in the mixed solvent of the tetracol phenixin of 2mL and acetonitrile (1: 1) after, add RuCl again
3(H
2O) (stirring at room 1.5 hours adds ether (5mL) and saturated sodium bicarbonate aqueous solution (5mL) for 2.1mg, aqueous solution 0.01mmol) (1.5mL).With sodium bicarbonate aqueous solution extraction (5mLx5), merge water, after 0 degree centigrade slowly adding concentrated hydrochloric acid adjust pH is 1 down,, merge organic phase, anhydrous Na with dichloromethane extraction (5mLx4)
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)：ν
max(cm
-1)＝2963，1732，1699，1514，1465，1423，1368，1263，1226，1167，1100，1011，801.
P27: fluoro Naproxen Base
Claims (8)
1, a kind of 3-disulfonyl base fluoromethane replacement-1-propene compound, it has the optical pure compound of following structural formula:
Wherein * is a chiral carbon atom, R
1Be selected from C arbitrarily
1-C
16Alkyl, C
3-C
16Cycloalkyl, C
4-C
10Heterocyclic 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; R is C
1-C
4Alkyl, C
1-C
4Perfluoroalkyl, halogen or C
1-C
4Alkoxyl group; R
2Be selected from C arbitrarily
1-C
16Alkyl, C
3-C
16Cycloalkyl; C
4-C
10Heterocyclic radical that contains N, O or S or C
4-C
10The heteroaryl that contains N, O or S, aryl; Described aryl is a phenyl or naphthyl.
2, a kind of synthetic method of optical activity 3-disulfonyl base fluoromethane replacement-1-propene compound as claimed in claim 1; it is characterized in that in organic solvent; under-20 ℃～120 ℃; with allyl carbonate ester compound and disulfonyl base fluoromethane compounds is 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 fluoromethane compounds, 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 fluoromethane compounds 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, 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; The perhaps combination of alkali and three fluosulfonic acid silver, lithium chloride or molecular sieve additive;
R wherein
1, R
2According to claim 1;
R
3, R
4Perhaps R
5Be selected from C arbitrarily
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 a 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 fluoromethane compounds, 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 the separation of products therefrom through recrystallization, thin-layer chromatography, column chromatography or underpressure distillation.
6, a kind of 3-disulfonyl base fluoromethane replacement-1-propene compound purposes as claimed in claim 1 is characterized in that being used to prepare the pharmaceutical intermediate with special physiological function of the aldehyde, alcohol, amine, carboxylic acid or the polynary ring that contain 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 a chiral carbon atom, R
1Be selected from C arbitrarily
1-C
16Alkyl, C
3-C
16Cycloalkyl; C
4-C
10Heterocyclic radical that contains N, O or S or the aryl that replaces of heteroaryl, aryl, R; Described aryl is a phenyl or naphthyl; R is C
1-C
4Alkyl, C
1-C
4Perfluoroalkyl, halogen or C
1-C
4Alkoxyl group.
8, purposes as claimed in claim 7, it is characterized in that in organic solvent, under-20 ℃～50 ℃, with 3-disulfonyl base fluoromethane replacement-1-propene compound is raw material, and 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 synthetic 3-of institute 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;
The 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
1According to 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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| CN102068422A (en) * | 2011-01-28 | 2011-05-25 | 中国科学院上海有机化学研究所 | Medical use of (S)-3-fluoro-2-(4-isobutyl phenyl) propionic acid |
| 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 |
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| CN100560555C (en) * | 2007-06-29 | 2009-11-18 | 中国科学院上海有机化学研究所 | A kind of synthetic 1, the method for 3-two replacement-4-alkene-1-cyclo-pentanone compounds |
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| CN102068422A (en) * | 2011-01-28 | 2011-05-25 | 中国科学院上海有机化学研究所 | Medical use of (S)-3-fluoro-2-(4-isobutyl phenyl) propionic acid |
| 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 |
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