CN104926720A - Chiral nitrogen-sulfur bidentate ligand and synthesis method and application thereof - Google Patents

Chiral nitrogen-sulfur bidentate ligand and synthesis method and application thereof Download PDF

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CN104926720A
CN104926720A CN201410100202.3A CN201410100202A CN104926720A CN 104926720 A CN104926720 A CN 104926720A CN 201410100202 A CN201410100202 A CN 201410100202A CN 104926720 A CN104926720 A CN 104926720A
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sulphur
chiral
bitooth ligand
nitrogen
chirality
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CN104926720B (en
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赵晓明
高宁
蔡成思
蔡爵旺
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Tongji University
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Abstract

The invention relates to a chiral nitrogen-sulfur bidentate ligand and a synthesis method and an application thereof. The chiral nitrogen-sulfur bidentate ligand is obtained by esterifying carboxylic acid firstly and then carrying out a reaction with chiral sulfinyl amine; the ligand is combined with a transition metal palladium, symmetrical allyl acetate is used as a substrate, dimethyl malonate and dimethyl fluoromalonate are used as nucleophilic reagents, and a chiral carbon-carbon bond is successfully constructed. Compared with the prior art, the chiral nitrogen-sulfur bidentate ligand has easily obtained synthetic raw materials, and the synthetic method is simple; the prepared chiral nitrogen-sulfur bidentate ligand is N-(sulphinyl)picolinamide with optical activity is applied in construction of the chiral carbon-carbon bond catalyzed by the transition metal palladium, the reaction conditions are mild, the operation is simple, in addition, the reaction yield is also better and is generally 78%-99%, and the enantioselectivity is high and has the highest value of 93%.

Description

A kind of chirality nitrogen-sulphur bitooth ligand and synthetic method thereof and application
Technical field
The present invention relates to a kind of chirality nitrogen-sulphur bitooth ligand and synthetic method thereof and application, belong to chipal compounds synthesis field.
Background technology
Chirality is a kind of general spontaneous phenomenon, greatly to the hand of spiral of galaxy in universe, and the little arrangement mode to different functional groups in molecule, all relevant with chirality.A lot of physiological activity has the participation of chiral material in organism, and chemical constitution is identical and similar substance that chirality is different, enters in organism and may have distinct effect.For " reaction stops " event, compound Thalidomide (Thalidomide) is put in European market as anti-gestation medicine by pharmaceutical factory, Germany, found that this medicine had strong teratogenesis to ewborn infant afterwards, research shows, containing chirality C-N key in Thalidomide molecule, medicine in putting goods on the market is racemic compound, the structure of R-(+) has maincenter sedative effect, the enantiomorph of another kind of configuration S-(-) then has strong teratogenecity, therefore, chirality factor contained in organic molecule causes the extensive attention of people, within 1992, U.S. FDA first formally discloses the chiral drug code administration guide being entitled as " statement of the policy of new stereoisomerism drug development ", European Union also disclosed the file of " chiral material research " in 1994 subsequently.
For organic chemist, after recognizing the importance of chirality, synthesizing single optically pure compound becomes an important research direction.How to obtain chiral material, usually have natural product derivatize, raceme chiral separation, microorganism catalysis, the several method such as enzyme catalysis and asymmetric synthesis.Wherein, dissymmetric synthesis is successfully applied to suitability for industrialized production.Chemist Noyori, Sharpless, Knowles, due to the contribution in asymmetric hydrogenation and oxidation, obtain calendar year 2001 Nobel chemistry Prize.【[1]Noyori，R.，Okhuma，T.；Kitamura，M.；Takaya，H.；Sayo，N.；Kumobayashi，H.；Akuragawa，S.J.Am.Chem.Soc.1987，109，5856.[2]Kitamura，M.；Tokunaga，M.；Ohkuma，T.；Noyori，R.Org.Syn.，Coll.Vo1.9，p.589(1998)；Vo1.71，p.1(1993).[3]Takaya，H.；Akutagawa，S.；Noyori，R.Org.Syn.，Coll.Vo1.8，p.57(1993)；Vo1.67，p.20(1989).[4]Noyori，Ryoji.Asymmetric Catalysis In Organic Synthesis.Wiley-Interscience.1994.[5]Ager，D.J.；Laneman，S.A.Tetrahedron：Asymmetry1997，8，3327.[6]Jacobsen，E.N.；Marko，I.；Mungall，W.S.；Schroeder，G.；Sharpless，K.B.J.Am.Chem.Soc.1988，110，1968.[7]Kolb，H.C.；Van Nieuwenhze，M.S.；Sharpless，K，B.Chem.Rev.1994，94，2483.[8]Gonzalez，J.；Aurigemma，C.；Truesdale，L. Org.Syn.，Coll.Vo1.10，p.603(2004)；Vo1.79，p.93(2002).[9]Minato，M.；Yamamoto，K.；Tsuji，J.J.Org.Chem.1990，55，766.[10]Oi，R.；Sharpless，K.B.Org.Syn.，Coll.Vo1.9，p.251(1998)；Vo1.73，p.1(1996).[11]VanRheenen，V.；Kelly，R.C.；Cha，D.Y.Tetrahedron Lett.1976，1973.[12]McKee，B.H.；Gilheany，D.G.；Sharpless，K.B.Org.Syn.，Coll.Vo1.9，p.383(1998)；Vo1.70，p.47(1992).[13]Jacobsen，E.N.；Marko，I.；Mungall，W.S.；Schroeder，G.；Sharpless，K.B.J.Am.Chem.Soc.1988，110，1968.[14]Gonzalez，J.；Aurigemma，C.；Truesdale，L. Org.Syn.，Coll.Vo1.10，p.603(2004)；Vo1.79，p.93(2002).[15]Sharpless，K.B.，et a1.J.Org.Chem.1992，57，2768.[16]Kolb，H.C.；van Nieuwenhze，M.S.；Sharpless，K.B.Chem.Rev.1994，94，2483-2547.[17]Corey，E.J.；Noe，M.C.；Grogan，M.J.Tetrahedron Lett.1996，37，4899.[18]DelMonte，A.J.；Haller，J.；Houk，K.N.；Sharpless，K.B.；Singleton，D.A.；Strassner，T.；Thomas，A.A.J.Am.Chem.Soc.1997，119，9907.[19]Ulf M. Rui Ding，Olle Efficient asymmetric synthesis of an azasugar in water.Chemical Communications.2005，13：1773.】
As mentioned above, realize organic asymmetric synthesis by metal catalytic, need to construct chiral environment in reaction process, chiral ligand just plays the effect forming chiral environment.From starting till now, chemist has synthesized the monodentate of various configuration, and bidentate and multiple tooth chiral ligand, be applicable to dissimilar asymmetric catalysis synthesis in asymmetric synthesis.However, in view of the complicacy of organic reaction, currently also do not find a kind of part with general applicability, this means will continue the exploratory development of the chiral ligand having no report.
Summary of the invention
Object of the present invention is exactly provide a kind of chirality nitrogen-sulphur bitooth ligand and synthetic method thereof and application to overcome defect that above-mentioned prior art exists.
Object of the present invention can be achieved through the following technical solutions:
A kind of chirality nitrogen-sulphur bitooth ligand, is specially optically active N-(sulfinyl) picolinamide, has following structural formula:
wherein * is chiral sulfur atom, R 1be selected from C arbitrarily 1-C 16alkyl, C 4-C 10the heterocyclic radical containing N, O or sulphur or C 4-C 10heteroaryl, aryl containing N, O or sulphur; R 2be selected from C arbitrarily 1-C 16alkyl or aryl.
A synthetic method for chirality nitrogen-sulphur bitooth ligand, in organic solvent, at-78 DEG C ~ 50 DEG C, pyridine carboxylic acid ester and chiral sulfenamide react 1-12 hour under alkali effect, obtained optically active N-(sulfinyl) picolinamide,
The mol ratio of described pyridine carboxylic acid ester, chiral sulfenamide and alkali is: (1-3): (0.01-0.5): (0.05-5):
The structural formula of described pyridine carboxylic acid ester is:
wherein, R 1be selected from C arbitrarily 1-C 16alkyl, C 4-C 10the heterocyclic radical containing N, O or sulphur or C 4-C 10heteroaryl, aryl containing N, O or sulphur, R 4be selected from C arbitrarily 1-C 16alkyl, C 4-C 10the heterocyclic radical containing N, O or sulphur or C 4-C 10heteroaryl, aryl containing N, O or sulphur; Described pyridine carboxylic acid ester obtains by after pyridine acid and analogue esterification thereof;
The structural formula of described chiral sulfenamide is: wherein * is chiral sulfur atom, R 2be selected from C arbitrarily 1-C 16alkyl or aryl;
Described alkali is alkalimetal hydride, alkaline earth metal hydride, lithium alkylide or lithium aryl.
Described organic solvent is selected from benzene, tetracol phenixin, trichloromethane, methylene dichloride, tetrahydrofuran (THF), DMF, ether, dioxane or acetonitrile a kind of.
The concrete reaction equation of N-(sulfinyl) picolinamide of synthesis of optically active is as follows:
Wherein, base is described various alkali, and solvent is described organic solvent.
Obtained optically active N-(sulfinyl) picolinamide is separated through the method for recrystallization, thin-layer chromatography, column chromatography or underpressure distillation.
During method with thin-layer chromatography, column chromatography, developping agent used is the mixed solvent of non-polar solvent and polar solvent.Recommend solvent to can be sherwood oil-methylene dichloride, petroleum ether-ethyl acetate, the mixed solvents such as sherwood oil-ether, its volume ratio can be respectively: non-polar solvent: polar solvent=100-20: 1.Such as: petrol ether/ethyl acetate=100-20/1, sherwood oil/methylene dichloride=100-20/1.
A kind of application of chirality nitrogen-sulphur bitooth ligand, described chirality nitrogen-sulphur bitooth ligand is applied in the asymmetric allylation of palladium chtalyst, specifically for (E)-2-(1,3-diaryl the allyl group)-2-fluoromalonic acid dimethyl ester compound of synthesis of optically active; Synthetic method is as follows: in organic solvent, and at-78 DEG C ~ 50 DEG C, temperature of reaction is preferably at-20 DEG C ~ 50 DEG C, with allyl acetic acid ester compound and fluoromalonic acid dimethyl ester for raw material, with [Pd (C 3h 5) Cl] 2combine with chirality nitrogen-sulphur bitooth ligand, under the effect of additive, react 2-48 hour obtained optically active (E)-2-(1,3-diaryl allyl group)-2-fluoromalonic acid dimethyl ester compound.
Described allyl acetic acid ester compound, fluoromalonic acid dimethyl ester, [Pd (C 3h 5) Cl] 2, chirality nitrogen-sulphur bitooth ligand and additive mol ratio be (1-3): (0.01-5): (0.02-0.1): (0.05-5): (0.05-5); The mol ratio of reaction is preferably 1: 3: 0.O1: 0.01: 3: 3.
The structural formula of described allyl acetic acid ester compound is: be selected from C arbitrarily 1-C 16alkyl, C 4-C 10the heterocyclic radical containing N, O or sulphur or C 4-C 10heteroaryl, aryl containing N, O or sulphur;
The structural formula of described fluoromalonic acid dimethyl ester is:
Described additive is selected from one or more in cesium carbonate, potassium acetate, cesium fluoride, cesium chloride, lithium chloride or tetra-n-butyl Neutral ammonium fluoride.
Described optically active (E)-2-(1,3-diaryl allyl group)-2-fluoromalonic acid dimethyl ester compound is the optical pure compound with following structural formula,
wherein * is chiral carbon atom, R 3be selected from C arbitrarily 1-C 16alkyl, C 4-C 10the heterocyclic radical containing N, O or sulphur or C 4-C 10heteroaryl, aryl containing N, O or sulphur.
Described organic solvent is selected from benzene, tetracol phenixin, trichloromethane, methylene dichloride, tetrahydrofuran (THF), N, N-dimethyl formamide, ether, dioxane or acetonitrile a kind of.
(E)-2-(1,3-diaryl allyl group) the concrete reaction equation of-2-fluoromalonic acid dimethyl ester compound of synthesis of optically active is as follows:
Wherein, L is optically active N-(sulfinyl) picolinamide, and addictive is described various additive or combination, and solvent is described organic solvent.
Obtained optically active (E)-2-(1,3-diaryl allyl group)-2-fluoromalonic acid dimethyl ester compound is separated through the method for recrystallization, thin-layer chromatography, column chromatography or underpressure distillation.
During method with thin-layer chromatography, column chromatography, developping agent used is the mixed solvent of non-polar solvent and polar solvent.Recommend solvent to can be sherwood oil-methylene dichloride, petroleum ether-ethyl acetate, the mixed solvents such as sherwood oil-ether, its volume ratio can be respectively: non-polar solvent: polar solvent=100-20: 1.Such as: petrol ether/ethyl acetate=100-20/1, sherwood oil/methylene dichloride=100-20/1.
Compared with prior art, the present invention has the following advantages and beneficial effect:
(1) chirality nitrogen of the present invention-sulphur bitooth ligand synthesis material is easy to get, and synthetic method is simple;
(2) chirality nitrogen-sulphur bitooth ligand that the present invention obtains is optically active N-(sulfinyl) picolinamide; the chirality C-C being applied to transition metal palladium chtalyst is constructed; reaction conditions is gentle; easy and simple to handle; the productive rate reacted in addition is better (being generally 78%-99%) also, enantioselectivity high (the highest by 93%).
Embodiment
Below in conjunction with specific embodiment, the present invention is described in detail.
Embodiment 1
The synthesis of chirality nitrogen-sulphur bitooth ligand
Compound 1 (pyridine-2,6-dioctyl phthalate, 5.0g, 30.O mmol) and 10mL methyl alcohol are added in 100mL egg type bottle, the instillation 10mL vitriol oil, reflux.After stopped reaction, add sodium carbonate and sulfuric acid reaction, when solution is neutrality, DCM extracts 3 times, and saturated common salt washes 1 time, adds anhydrous sodium sulfate drying.Suction filtration, is spin-dried for organic solvent and obtains compound 1a.
Compound 1a (4.0g, 20.5mmol), 30mL methyl alcohol and 20mL methylene dichloride are added in 250mL there-necked flask, adds NaBH 4(0.86g, 22.4mmol), stirring reaction.After stopped reaction, be spin-dried for solvent, cross post and be separated, obtain compound 2a.
NaH (0.36g, 15.0mmol) and 20mL tetrahydrofuran (THF) are added in reaction tubes, stirs into suspension liquid, by compound 2a (2.0g, 12.0mmol) add in reaction tubes, stir after 1 hour, add allyl bromide 98 (1.8g, 15.0mmol), after reaction terminates, suction filtration solid, rotary evaporation falls solvent, cross post to be separated, obtain compound 3f.
By (R)-t-butyl sulfonamide (0.30g, 2.5mmol), KH (0.10g, 2.5mmol) and 15mL tetrahydrofuran (THF) add in reaction tubes, stirring reaction 1 hour, add compound 3f (0.52g, 2.5mmol), after reaction terminates, suction filtration, be spin-dried for, cross post and be separated, obtain compound 4f.
Embodiment 2 ~ 19
The research of the additive of the asymmetric allyl reaction of palladium chtalyst, solvent and part
Wherein mol refers to mole, and Base refers to alkali, and Solvent refers to solvent, and Ligand assigns body, and Time refers to the time, and equiv. refers to equivalent, and ee refers to percent enantiomeric excess.
In the reaction tubes of the argon shield of a drying, add 4.0mol% [Pd (C successively 3h 5) Cl] 28.0mol% part, stirring at room temperature 30 minutes, then 1.0equiv.5a (0.2mmol) is added, continue stirring 10 minutes, simultaneously by the Base of 3.0equiv.6a (1.5mmol) and 3.0equiv. in another side reaction pipe, the pre-prepared nucleophilic reagent of stirring reaction in 1.5Solvent solvent, nucleophilic reagent is added in catalyzer, stirring reaction.After reaction terminates, after removal of solvent under reduced pressure, residue thin-layer chromatography obtains target product (sherwood oil/methylene dichloride=1/1, or petrol ether/ethyl acetate=10/1, v/v).
Different ligands is as follows:
Different ligands, organic solvent, alkali and under the reaction times, the situation of obtained product 7a is as table 1shown in,
Table 1
The ingredient proportion that [a] reacts in all kinds of SOLVENTS is: 4.0mol% [Pd (C 3h 5) Cl] 2, 8.0mol%ligand, 1.0equiv.5a (0.2mmol), the Base of 3.0equiv.6a (1.5mmol) and 3.0equiv. reacts in 2.5mLSolvent under room temperature.
[b] refers to separation yield.
[c] refers in embodiment 17, with Pd (dba) 2substitute [Pd (C 3h 5) Cl] 2as catalyzer.
[d] refers in embodiment 18, and organic solvent is the KOAc of 3.0equiv.of BSA (N, O-Bis (trimethylsilyl) acetamide, 0.6mmo1) and 4mol%.
[e] refers in embodiment 19, and organic solvent is the NaOAc of 3.0equiv.of BSA (N, O-Bis (trimethylsilyl) acetamide, 0.6mmol) and 4mol%.
[f] refers to that percent enantiomeric excess (ee) is measured by Chiral liquid chromatography.
Wherein: solvent DCM is methylene dichloride, PhMe is toluene, and THF is tetrahydrofuran (THF); Trace refers to there is a small amount of product.
Embodiment 20 ~ 30
The asymmetric allyl reaction suitability of the fluoromalonic acid dimethyl ester nucleophilic of palladium chtalyst
Wherein mol refers to mole, and Base refers to alkali, and Solvent refers to solvent, and Time refers to the time, and Ligand assigns body (compound 4f), and equiv. refers to equivalent.
In the reaction tubes of the argon shield of a drying, add 4.0mol% [Pd (C successively 3h 5) Cl] 2, 8.0mol% part, stirring at room temperature 30 minutes, then 1.0equiv.5 (0.2mmol) is added, continue stirring 10 minutes, the Base (1.5mmol) of 3.0equiv.8 (1.5mmol) and 3.0equiv. is added in reaction tubes, stirring reaction.After reaction terminates, after removal of solvent under reduced pressure, residue thin-layer chromatography obtains target product (sherwood oil/methylene dichloride=1/1, or petrol ether/ethyl acetate=10/1, v/v).
Wherein: solvent DCM is methylene dichloride, PhMe is toluene, and THF is tetrahydrofuran (THF); Trace refers to there is a small amount of product.
Under different ligands, organic solvent, alkali and starting compound 5, reaction times, the situation of obtained product 9 is as shown in table 1,
Table 2
The ingredient proportion that [a] reacts in all kinds of SOLVENTS is: 4.0mol% [Pd (C 3h 5) Cl] 2, 8.0mol%ligand, 1.0equiv.5 (0.2mmol), the Cs of 3.0equiv.8 (1.5mmol) and 3.0equiv. 2cO 3react under room temperature in 2.5mL solvent.
[b] refers to the separation yield of compound 9.
[c] refers to that percent enantiomeric excess (ee) is measured by Chiral liquid chromatography.
[d] refers to use (S, S)-DACH-naphthyl Trost Ligand alternative compounds 4f as part in embodiment 22.
Embodiment related products physical property characterize and yield as follows:
P1:6-(allyl methoxyl) pyridine carboxylic acid methyl esters
Weak yellow liquid, 56% yield.
1H NMR(400MHz，CDCl 3)δ＝8.04(d，J＝7.6Hz，1H)，7.87(dd，J＝8.0，7.6Hz，1H)，7.72(d，J＝8.0Hz，1H)，5.98(ddd，J＝17.2，10.4，5.6Hz，1H)，5.35(d，J＝17.2Hz，1H)，5.24(d，J＝10.0Hz，1H)，4.76(s，2H)，4.14(d，J＝5.2Hz，1H)，4.00(s，3H)。
13C NMR(100MHz，CDCl 3)δ＝165.6，159.4，147.1，137.4，134.1，124.3，123.6，117.3，72.6，71.8，52.7。
HRMS(ESI)calcd for C 11H 13NNaO 3([M+Na] +)：230.0793，Found：230.0788。
IR(KBr)：v max(cm -1)＝3853，3801，3741，3628，2951，2916，2848，2359，1456，1437，1314，1292，1227，1138，1081，992，927，761。
P2:6-(trityl methoxyl group) pyridine carboxylic acid methyl esters
White solid, 78% yield.
m.p.100.4-101.5℃。
1H NMR(400MHz，CDCl 3)δ＝8.05-7.99(m，2H)，7.91-7.85(m，1H)，7.51-7.48(m，6H)，7.32-7.20(m，9H)，4.51(s，2H)，3.94(s，3H)。
13C NMR(100MHz，CDCl 3)δ＝165.6，160.1，146.9，143.6，137.5，128.5，127.9，127.1，123.8，124.4，87.4，66.8，52.8。
HRMS(EI)calcd for C 27H 23NNaO 3([M+Na] +)：432.1576，Found：432.1570。
IR(KBr)：v max(cm -1)＝3853，3837，3801，3744，3675，3649，3058，3031，2949，1743，1724，1683，1652，1591，1575，1506，1409，1447，1384，1359，1313，1292，1225，1193，1151，1137，1095，1076，1032，991，899，763，746，649，632.
P3:(R)-N-(terf-butylsulfinyl) picolinamide
White solid, 90% yield.
m.p.68.4-70.5℃。
[α] D 20-28.3°(c1.0，CHCl 3)。
1H NMR(400MHz，CDCl 3)δ＝9.62-9.54(m，1H)，8.64(d，J＝4.0Hz，1H)，8.20(d，J＝8.0Hz，1H)，7.96(dd，J＝7.6，7.6Hz，1H)，7.59(dd，J＝7.2，6.4Hz，1H)，1.39(s，9H)。
13C NMR(100MHz，CDCl 3)δ＝164.2，148.1，147.4，137.4，127.2，122.3，56.3，21.6。HRMS(ESI)calcd for C 10H 14N 2NaO 2S([M+Na] +)：249.0647，Found：249.0598。
IR(KBr)：v max(cm -1)＝3676，3413，3304，3058，2967，2869，1703，1638，1590，1449，1389，1292，1269，1185，1106，1080，1040，998，871，818，788，737，697，620.
P4:(R)-N-(terf-butylsulfinyl) quinoline-2-carboxylic acid amides
White solid, 58% yield.
m.p.155.7-156.2℃。
[α] D 20-56.4°(c1.0，CHCl 3). 1H NMR(400MHz，CDCl 3)δ＝9.76-9.70(m，1H)，8.35(d，J＝8.4Hz，1H)，8.27(d，J＝8.4Hz，1H)，8.11(d，J＝8.0Hz，1H)，7.90(d，J＝8.0Hz，1H)，7.81(dd，J＝7.6，7.6Hz，1H)，7.59(dd，J＝7.6，7.2Hz，1H)，7.67(dd，J＝7.6，7.2Hz，1H)，1.42(s，9H)。
13C NMR(100MHz，CDCl 3)δ＝164.8，147.6，146.2，137.9，130.5，129.8，129.6，128.7，127.7，118.6，57.1，22.0.HRMS(ESI)calcd for C 14H 16N 2NaO 2S([M+Na] +)：299.0830，Found：299.0769。
IR(KBr)：v max(cm -1)＝3853，3747，2962，1844，1700，1651，1558，1540，1488，1396，1362，1340，1262，1099，1075，1013，903，847，763。
P5:(R)-N-(terf-butylsulfinyl) isoquinoline 99.9-1-carboxylic acid amides
White solid, 43% yield.
m.p.61.4-64.6℃。
[α] D 20-312.0°(c1.0，CHCl 3). 1H NMR(400MHz，CDCl 3)δ＝10.00-9.95(m，1H)，9.54(d，J＝8.0Hz，1H)，8.50(d，J＝5.2Hz，1H)，7.90-7.87(m，2H)，7.78-7.69(m，2H)，1.41(s，9H)。
13C NMR(100MHz，CDCl 3)δ＝166.0，145.2，140.1，137.4，130.7，129.4，127.1，127.0，126.9，125.8，56.8，22.1。
HRMS(ESI)calcd for C 14H 16N 2NaO 2S([M+Na] +)：299.0830，Found：299.0824。
IR(KBr)：v max(cm -1)＝3853，3801，3747，3710，3649，3056，2963，2922，1698，1370，1330，1083，847，749。
P6:(R)-N-(terf-butylsulfinyl)-6-picoline acid amides
White solid, 18% yield.
m.p.127.8-128.7℃。
[α] D 20-133.3°(c0.9，CHCl 3). 1H NMR(400MHz，CDCl 3)δ＝9.62-9.52(m，1H)，8.02(d，J＝7.6Hz，1H)，7.78(dd，J＝8.0，7.6Hz，1H)，7.37((d，J＝7.2Hz，1H)，2.59(s，3H)，1.37(s，9H)。
13C NMR(100MHz，CDCl 3)δ＝164.9，157.7，147.4，137.8，127.2，120.0，57.0，24.2，22.1。
HRMS(ESI)calcd for C 11H 16N 2NaO 2S([M+Na] +)：263.0830，Found：263.0825。
IR(KBr)：v max(cm -1)＝3853，3801，3747，3710，3649，2923，1734，1701，1651，1595，1558，1540，1393，1362，1259，1186，1091，1072，994，848，826，753，601。
P7:(R)-N-(terf-butylsulfinyl)-6-phenylpyridine acid amides
White solid, 67% yield.
m.p.130.8-131.9℃。
[α] D 20-282.0°(c0.5，CHCl 3). 1H NMR(400MHz，CDCl 3)δ＝9.71-9.62(m，1H)，8.17(d，J＝8.4Hz，1H)，8.00-7.96(m，4H)，7.55-7.48((m，3H)，1.39(s，9H)。
13C NMR(100MHz，CDCl 3)δ＝164.7，156.4，147.8，138.6，137.7，129.8，129.0，126.8，124.3，121.3，57.0，22.1。
HRMS(ESI)calcd for C 11H 16N 2NaO 3S([M+Na] +)：325.0987，Found：325.0981。
IR(KBr)：v max(cm -1)＝3853，3747，3673，3629，3063，2963，1702，1460，1389，1185，1085，848，814，751，604。
P8:(R)-6-(allyl methoxyl)-N-(terf-butylsulfinyl) picolinamide
Weak yellow liquid, 58% yield.
[α] D 20-52.9°(c1.0，CHCl 3)。
1H NMR(400MHz，CDCl 3)δ＝9.52-9.44(m，1H)，8.11(d，J＝7.6Hz，1H)，7.94(dd，J＝8.0，7.6Hz，1H)，7.30(d，J＝7.6Hz，1H)，5.98(ddd，J＝19.4，10.8，5.6Hz，1H)，5.37(d，J＝17.2Hz，1H)，5.26(d，J＝10.4Hz，1H)，4.68(s，2H)，4.15(d，J＝5.6Hz，1H)，1.37(s，9H)。
13C NMR(100MHz，CDCl 3)δ＝164.3，157.9，146.9，138.2，133.9，125.0，121.3，117.3，72.0，71.7，56.8，21.8。
HRMS(ESI)calcd for C 14H 20N 2NaO 3S([M+Na] +)：319.1092，Found：319.1084。
IR(KBr)：v max(cm -1)＝3901，3853，3801，3747，3649，1734，1700，1685，1651，1472，1395，1361，1261，1072，829，752，595。
P9:(R)-6-(Bian ylmethoxy)-N-(terf-butylsulfinyl) picolinamide
White solid, 39% yield.
m.p.86.5-87.8℃。
[α] D 20-289.6°(c0.7，CHCl 3). 1H NMR(400MHz，CDCl 3)δ＝9.46-9.38(m，1H)，8.12(d，J＝7.6Hz，1H)，7.92(dd，J＝7.6，7.6Hz，1H)，7.75(d，J＝8.0Hz，1H)，7.41-7.32(m，5H)，4.70(s，2H)，4.68(s，2H)，1.35(s，9H)。
13C NMR(100MHz，CDCl 3)δ＝164.5，158.0，147.2，138.3，137.5，128.5，127.9，127.7，125.2，121.6，73.0，72.3，57.0，22.0。
HRMS(ESI)calcd for C 18H 22N 2NaO 3S([M+Na] +)：369.1249，Found：369.1244。
IR(KBr)：v max(cm -1)＝3853，3747，3673，3649，3064，2286，1734，1700，1651，1558，1540，1393，1361，1261，1071，995，848，824，751，602。
P10:(R)-N-(terf-butylsulfinyl)-6-((naphthalene-1-methyl methoxy base)) picolinamide
Thick liquid, 26% yield.
[α] D 20-18.5°(c3.0，CHCl 3)。
1H NMR(400MHz，CDCl 3)δ＝9.46-9.38(m，1H)，8.13(d，J＝8.4Hz，1H)，8.07(d，J＝7.6Hz，1H)，7.87-7.79(m，1H)，7.67(d，J＝7.6Hz，1H)7.56-7.42(m，4H)，5.13-5.06(m，2H)，4.73(s，2H)，1.32(s，9H)。
13C NMR(100MHz，CDCl 3)δ＝164.4，157.9，147.0，138.2，133.6，132.8，131.5，128.8，126.5，126.2，125.7，125.2，125.0，123.7，121.472.2，71.5，56.9，21.9。
HRMS(ESI)calcd for C 22H 24N 2NaO 3S([M+Na] +)：419.1405，Found：419.1411。
IR(KBr)：v max(cm -1)＝3301，3051，2962，2866，1702，1594，1510，1466，1394，1363，1268，1231，1166，1092，1072，1015，996，827，795，777，751，736，598。
P11:(dog)-N-(terf-butylsulfinyl)-6-(trityl methoxyl group) picolinamide
White solid, 54% yield.
m.p.62.0-64.7℃。
[α] D 20-342.7°(c1.0，CHCl 3)。
1H NMR(400MHz，CDCl 3)δ＝9.46-9.38(m，1H)，8.13(d，J＝8.4Hz，1H)，8.07(d，J＝7.6Hz，1H)，7.87-7.79(m，1H)，7.67(d，J＝7.6Hz，1H)7.56-7.42(m，4H)，5.13-5.06(m，2H)，4.73(s，2H)，1.32(s，9H)。
13C NMR(100MHz，CDCl 3)δ＝164.6，158.5，147.0，143.5，138.2，128.6，128.0，127.3，125.0，121.3，87.5，66.4，57.0，22.0。
HRMS(ESI)calcd for C 30H 30N 2NaO 3S([M+Na] +)：521.1875，Found：521.1870。
IR(KBr)：v max(cm -1)＝3853，3747，3673，3649，3566，3478，3058，2924，1734，1700，1651，1594，1558，1394，1362，1262，1216，1069，992，899，848，825，751，705，632，604。
P12:(R)-N-((R) terf-butylsulfinyl)-2-phenyl-4,5-dihydro-oxazole-4-carboxylic acid amides
White solid, 30% yield.
m.p.140.5-141.4℃。
[α] D 20-141.2°(c2.0，CHCl 3)。
1H NMR(400MHz，CDCl 3)δ＝8.21-8.15(m，1H)，7.96-7.94(m，2H)，7.56-7.52(m，1H)，7.46-7.42(m，2H)，4.92(dd，J＝9.6，9.6Hz，1H)4.74-4.67(m，2H)，1.33(s，9H)。 13C NMR(100MHz，CDCl 3)δ＝172.3，166.4，132.2，128.5，128.3，126.4，69.7，69.5，56.8，21.9。
HRMS(ESI)calcd for C 14H 18N 2NaO 3S([M+Na] +)：317.0936，Found：317.0926。
IR(KBr)：v max(cm -1)＝3853，3837，3747，3673，3648，3474，3065，2962，2922，2851，1701，1639，1577，1558，1393，1362，1293，1172，1088，1069，1026，963，893，847，784，694，605。
P13:(S)-N-((R) terf-butylsulfinyl)-2-phenyl-4,5-dihydro-oxazole-4-carboxylic acid amides
White solid, 21% yield.
m.p.152.7-154.1℃。
[α] D 20-247.5°(c1.0，CHCl 3)。
1H NMR(400MHz，CDCl 3)δ＝8.31-8.20(m，1H)，7.98-7.96(m，2H)，7.57-7.53(m，1H)，7.48-7.43(m，2H)，4.97(dd，J＝10.4，10.0Hz，1H)4.71-4.66(m，2H)，1.24(s，9H)。
13C NMR(100MHz，CDCl 3)δ＝172.6，167.2，132.3，128.5，126.4，69.7，69.1，56.9.22.0。
HRMS(ESI)calcd for C 14H 18N 2NaO 3S([M+Na] +)：317.0936，Found： 317.0923。
IR(KBr)：v max(cm -1)＝3547，3476，3413，3118，2963，2919，2850，1711，1640，1358，1296，1258，1239，1155，1086，1063，1027，971，953，895，817，786，751，699，609。
P14:(S)-N-((R) terf-butylsulfinyl)-2-phenyl-4,5-thiazoline-4-carboxylic acid amides
White solid, 14% yield.
m.p.129.5-130.8℃。
[α] D 20-33.6°(c1.0，CHCl 3)。
1H NMR(400MHz，CDCl 3)δ＝8.43-8.20(m，1H)，7.84-7.81(m，2H)，7.55-7.51(m，1H)，7.47-7.42(m，2H)，5.25(dd，J＝10.0，10.0Hz，1H)3.80-3.67(m，2H)，1.34(s，9H)。
13C NMR(100MHz，CDCl 3)δ＝172.5，172.2，132.1，132.0，128.6，128.3，79.356.9，34.7，22.0。
HRMS(ESI)calcd for C 14H 18N 2NaO 2S 2([M+Na] +)：333.0707，Found：333.0700。
IR(KBr)：v max(cm -1)＝3853，3747，3673，3648，3548，3476，3414，3236，17001637，1617，1558，1541，1260，1087，940，849，764，610。
P15:(R)-N-((R) terf-butylsulfinyl)-2-phenyl-4,5-thiazoline-4-carboxylic acid amides
White solid, 25% yield.
m.p.107.8-108.6℃。
[α] D 20+34.2°(c0.9，CHCl 3)。
1H NMR(400MHz，CDCl 3)δ＝8.39-8.25(m，1H)，7.92-7.79(m，2H)，7.60-7.40(m，3H)，5.40-5.27(m，1H)3.81-3.69(m，2H)，1.23(s，9H)。
13C NMR(100MHz，CDCl 3)δ＝172.1，171.9，132.2，132.1，128.8，128.3，79.4，56.9，34.9，21.9。
HRMS(ESI)calcd for C 14H 18N 2NaO 2S 2([M+Na] +)：333.0707，Found：333.0705。
IR(KBr)：v max(cm -1)＝3853，3801，3747，3710，3629，2922，1734，1700，1651，1558，1540，1260，1083，1037，938，849，764，605。
P16:(R)-N-(terf-butylsulfinyl)-2-(diphenylphosphine) benzamide
White solid, 42% yield.
m.p.165.2-167.2℃。
[α] D 20-141.2°(c2.0，CHCl 3)。
1H NMR(400MHz，CDCl 3)δ＝8.40-8.28(m，1H)，7.79-7.76(m，1H)，7.43-7.31(m，8H)，7.26-7.20(m，4H)7.01-6.98(m，1H)，1.19(s，9H)。
13C NMR(100MHz，CDCl 3)δ＝169.2，138.7(d，J C-P＝25.5Hz)，136.1(ddd，J C-P＝21.2，11.7，9.5Hz)，134.4，133.8(d，J C-P＝19.7Hz)，133.6(d，J C-P＝19.6Hz)，131.2，130.0，128.9，128.8(d，J C-P＝5.1Hz)，128.6(dd，J C-P＝7.3，6.6Hz)，57.3，22.0。
31P NMR(162MHz，CDCl 3)δ＝-10.40。
HRMS(ESI)calcd for C 23H 24NqaO 2PS([M+Na] +)：432.1163，Found：432.1152。
IR(KBr)：v max(cm -1)＝3853，3747，3673，3649，3476，3054，1734，1682，1559，1387，1264，1237，1182，1067，870，848，748，695，608。
P17:(E)-2-(1,3-bis-(naphthalene-1-base) allyl group)-2-fluoromalonic acid dimethyl ester
White solid, 78% yield, 80%ee [Diacel CHIRALPAK AD-H (0.46cmx25cm); Normal hexane/Virahol=80/20, flow velocity=0.8mL/min, determined wavelength=214nm; t r=9.80min (minor), 23.02min (major)].
m.p.106.3-108.2℃。
[α] D 20-63.6°(c3.0，CHCl 3)。
1H NMR(400MHz，CDCl3)δ＝8.36(d，J＝8.8Hz，1H)，7.96(d，J＝7.6Hz，1H)，7.87-7.84(m，2H)，7.80-7.77(m，2H)，7.72(d，J＝8.0Hz，1H)，7.62-7.58(m，1H)，7.51-7.33(m，7H)，6.51(dd，J＝15.2，8.4Hz，1H)，5.33(dd，J＝9.6，9.6Hz，1H)，5.69(dd，J＝40.0，9.2Hz，1H)，3.74(s，3H)，3.44(s，3H)。
19F NMR(100MHz，CDCl3)δ＝-174.10。
13C NMR(126MHz，CDCl 3)δ＝166.1(d，J C-F＝25.7Hz)，165.1(d，J C-F＝26.7Hz)，134.3，134.0，133.4，132.9，131.9，131.3，131.0，129.0，128.45，128.39，128.2，126.64，126.60，126.3，126.0，125.7，125.6，125.54，125.48，124.1，123.6，123.1，97.9(d，.J C-F＝210.3Hz)，53.6，53.0，47.6(d，J C-F＝18.4Hz)。
HRMS(ESI)calcd for C 28H 23FNa0 4([M+Na] +)：465.1478，Found：465.1482。
IR(KBr)：v max(cm -1)＝3853，3747，3673，3648，3479，3053，2954，2847，1761，1650，1594，1558，1509，1435，1396，1262，1169，1142，1086，1044，969，848，797，778，736，679，602。
P18:(E)-2-(1,3-bis-isophthalic methacrylic)-2-fluoromalonic acid dimethyl ester
White solid, 83% yield, 77%ee [Diacel CHIRALPAK AD-H (0.46cm x25cm); Normal hexane/Virahol=80/20, flow velocity=0.8mL/min, determined wavelength=254nm; t r=9.98min (major), 11.28min (minor)].
m.p.97.7-99.4℃。
[α] D 20+45.0°(c2.0，CHCl 3)。
1H NMR(400MHz，CDCl 3)δ＝7.23-7.12(m，6H)，7.07-7.02(m，2H)，6.54(d，J＝15.6Hz，1H)，6.44(dd，J＝15.6，9.2Hz，1H)，4.48(dd，J＝31.2，8.8Hz，1H)， 3.80(s，3H)，3.61(s，3H)，2.33(s，3H)，2.31(s，3H)。
19F NMR(100MHz，CDCl3)δ＝-175.76。
13C NMR(126MHz，CDCl 3)δ＝165.6(d，J C-F＝25.7Hz)，165.2(d，J C-F＝25.7Hz)，138.1，138.0，136.7，136.4，134.2，129.7，128.6，128.5，128.4，128.3，127.1，126.0，124.5(d，J＝3.7Hz)，123.7，97.5(d，J C-F＝210.3Hz)，53.8(d，J C-F＝18.3Hz)，53.4，53.0，21.4，21.2。
HRMS(ESI)calcd for C 22H 23FNaO 4([M+Na] +)：393.1478，Found：393.1473。
IR(KBr)：v max(cm -1)＝3853，3747，3673，3649，3031，2955，1763，1700，1650，1604，1558，1549，1489，1261，1140，1047，967，849，777，707，607。
P19:(E)-2-(1,3-, bis-pairs of phenmethyl allyl groups)-2-fluoromalonic acid dimethyl ester
White solid, 69% yield, 80%ee [Diacel CHIRALPAK AD-H (0.46cm x25cm); Normal hexane/Virahol=80/20, flow velocity=0.8mL/mi n, determined wavelength=254nm; t r=14.63min (major), 15.76min (minor)].
m.p.83.9-84.8℃。
[α] D 20+66.8°(c1.0，CHCl 3)。
1H NMR(400MHz，CDCl 3)δ＝7.27-7.21(m，4H)，7.13-7.07(m，4H)，6.53(d，J＝16.0Hz，1H)，6.40(dd，J＝15.6，8.8Hz，1H)，4.48(dd，J＝31.6，8.8Hz，1H)，3.80(s，3H)，3.61(s，3H)，2.33(s，3H)，2.31(s，3H)，2.30(s，3H)。
19F NMR(100MHz，CDCl 3)δ＝-176.00。
13C NMR(100MHz，CDCl 3)δ＝165.7(d，J C-F＝25.5Hz)，165.2(d，J C-F＝26.2Hz)，137.6，137.4，133.9，133.74，133.69，129.3，129.1，128.9，126.4，123.7(d，J C-F＝2.9Hz)，97.6(d，J C-F＝208.0Hz)，53.5(d，J C-F＝18.2Hz)，53.4，53.1，21.1，21.0。
HRMS(ESI)calcd for C 22H 23FNaO 4([M+Na] +)：393.1478，Found：393.1477。
IR(KBr)：v max(cm -1)＝3853，3747，3673，3648，3027，2954，1762，1650，1616，1558，1512，1257，1139，1045，969，848，806，586。
P20:(E)-2-(1,3-bis-(3-bromophenyl) allyl group)-2-fluoromalonic acid dimethyl ester
White solid, 99% yield, 90%ee [Diacel CHIRALPAK AD-H (0.46cm x25cm); Normal hexane/Virahol=80/20, flow velocity=0.8mL/min, determined wavelength=254nm; t r=12.93min (minor), 13.94min (major)].
m.p.93.9-95.4℃。
[α] D 20+63.5°(c2.0，CHCl 3)。
1H NMR(400MHz，CDCl 3)δ＝7.53-7.48(m，2H)，7.43-7.41(m，1H)，7.37-7.32(m，2H)，7.26-7.13(m，3H)，6.50(d，J＝15.6Hz，1H)，6.41(dd，J＝16.0，8.8Hz，1H)，4.50(dd，J＝30.8，8.8Hz，1H)，3.83(s，3H)，3.65(s，3H)。
19F NMR(100MHz，CDCl 3)δ＝-175.46。
13C NMR(100MHz，CDCl 3)δ＝165.2(d，J C-F＝25.5Hz)，164.8(d，J C-F＝25.6Hz)，138.6，138.2，133.3，132.0，131.0，130.9，130.2，130.0，129.3，127.6，125.4(d，J C-F＝4.4Hz)，125.2，122.7，122.6，98.5(d，J C-F＝208.7Hz)，53.7，53.4，53.1(d，J C-F＝18.3Hz)。
HRMS(ESI)calcd for C 20H 17Br 2FNaO 4([M+Na] +)：520.9375，Found：520.9370。
IR(KBr)：v max(cm -1)＝3901，3747，3648，3549，3479，3414，3236，3060，2954，1759，1716，1699，1636，1617，1559，1540，1473，1457，1434，1260，1141，1072，1048，967，767，748，606。
P21:(E)-2-(1,3-bis-(4-fluorophenyl) allyl group)-2-fluoromalonic acid dimethyl ester
White solid, 93% yield, 90%ee [Diacel CHIRALPAK AD-H (0.46cm x25cm); Normal hexane/Virahol=80/20, flow velocity=0.8mL/min, determined wavelength=254nm; t r=13.83min (major), 15.31min (minor)].
m.p.90.7-92.1℃。
[α] D 20+63.5°(c2.0，CHCl 3)。
1H NMR(400MHz，CDCl 3)δ＝7.38-7.29(m，4H)，7.04-6.95(m，4H)，6.52(d，J＝15.6Hz，1H)，6.34(dd，J＝15.6，9.2Hz，1H)，4.52(dd，J＝31.2，9.2Hz，1H)，3.82(s，3H)，3.62(s，3H)。
19F NMR(100MHz，CDCl 3)δ＝-176.00，-114.17，-113.65。
13C NMR(126MHz，CDCl 3)δ＝165.5(d，J C-F＝25.7Hz)，165.0(d，J C-F＝25.7Hz)，162.5(d，J C-F＝248.0Hz)，162.3(d，J C-F＝247.8Hz)，133.2，132.4(dd，J C-F＝7.4，3.8Hz)，130.7(dd，J C-F＝8.3，2.8Hz)，128.1，128.0，127.2，115.5(d，J C-F＝21.2Hz)，115.4(d，J C-F＝22.0Hz)，97.4(d，J C-F＝210.3Hz)，53.5，53.2，52.9(d，J C-F＝18.3Hz)。
HRMS(ESI)calcd for C 20H 17F 3NaO 4([M+Na] +)：230.0793，Found：230.0788。
IR(KBr)：v max(cm -1)＝3853，3747，3673，3629，3043，1759，1716，1699，1651，1601，1558，1508，1229，1160，1041，970，848，827，790，750，606。
P22:(E)-2-(1,3-bis-(4-chloro-phenyl-) allyl group)-2-fluoromalonic acid dimethyl ester
White solid, 88% yield, 90%ee [Diacel CHIRALPAK AD-H (0.46cm x25cm); Normal hexane/Virahol=80/20, flow velocity=0.8mL/min, determined wavelength=254nm; t r=18.06min (major), 20.81min (minor)].
m.p.103.7-105.5℃。
[α] D 20+69.7°(c2.0，CHCl 3)。
1H NMR(400MHz，CDCl 3)δ＝7.34-7.25(m，8H)，6.51(d，J＝16.0Hz，1H)，6.39(dd，J＝15.6，9.2Hz，1H)，4.52(dd，J＝31.2，8.8Hz，1H)，3.82(s，3H)，3.63(s，3H)。 19F NMR(100MHz，CDCl 3)δ＝-175.70。
13C NMR(126MHz，CDCl 3)δ＝165.3(d，J C-F＝25.7Hz)，164.9(d，J C-F＝25.7Hz)，135.0，134.7，133.8，133.7，133.3，130.4，128.8，128.7，127.7，124.8(d，J C-F＝ 3.6Hz)，97.1(d，J C-F＝210.3Hz)，53.5，53.3，53.0(d，J C-F＝18.2Hz)。
HRMS(ESI)calcd for C 20H 17C1 2FNaO 4([M+Na] +)：433.0386，Found：433.0380。
IR(KBr)：V max(cm -1)＝3547，3476，3413，2955，1760，1638，1617，1491，1435，1254，1140，1092，1048，1014，970，826，803，725，625，567。
P23:(E)-2-(1,3-bis-(4-bromophenyl) allyl group)-2-fluoromalonic acid dimethyl ester
White solid, 86% yield, 91%ee [Diacel CHIRALPAK AD-H (0.46cm x25cm); Normal hexane/Virahol=80/20, flow velocity=0.8mL/min, determined wavelength=254nm; t r=21.86min (major), 26.72min (minor)].
m.p.71.0-72.6℃。
[α] D 20+30.9(c3.0，CHCl 3)。
1H NMR(400MHz，CDCl 3)δ＝7.46-7.44(m，2H)，7.41-7.38(m，2H)，7.27-7.25(m，2H)，7.20-7.18(m，2H)，6.49(d，J＝15.6Hz，1H)，6.40(dd，J＝15.6，8.8Hz，1H)，4.50(dd，J＝30.8，8.4Hz，1H)，3.81(s，3H)，3.63(s，3H)。
19F NMR(100MHz，CDCl 3)δ＝-175.70。
13C NMR(100MHz，CDCl 3)δ＝165.2(d，J C-F＝25.6Hz)，164.8(d，J C-F＝25.5Hz)，135.4，135.0，133.4，131.7，131.6，130.7，130.0，124.8，122.0，121.8，97.0(d，J C-F＝208.7Hz)，53.5，53.3，53.0(d，J C-F＝18.2Hz)。
HRMS(ESI)calcd for C 20H 17Br 2FNaO 4([M+Na] +)：520.9375，Found：520.9375。
IR(KBr)：v max(cm -1)＝3853，3747，3673，3477，1759，1716，1699，1650，1617，1558.1541，1487，1254，1140，1072，1010，969，848，799，766，721，612。
Above-mentioned is can understand and use invention for ease of those skilled in the art to the description of embodiment.Person skilled in the art obviously easily can make various amendment to these embodiments, and General Principle described herein is applied in other embodiments and need not through performing creative labour.Therefore, the invention is not restricted to above-described embodiment, those skilled in the art, according to announcement of the present invention, do not depart from improvement that scope makes and amendment all should within protection scope of the present invention.

Claims (10)

1. chirality nitrogen-sulphur bitooth ligand, is characterized in that, is specially optically active N-(sulfinyl) picolinamide, has following structural formula:
wherein * is chiral sulfur atom, R 1be selected from C arbitrarily 1-C 16alkyl, C 4-C 10the heterocyclic radical containing N, O or sulphur or C 4-C 10heteroaryl, aryl containing N, O or sulphur; R 2be selected from C arbitrarily 1-C 16alkyl or aryl.
2. the synthetic method of chirality nitrogen-sulphur bitooth ligand as claimed in claim 1; it is characterized in that; in organic solvent; at-78 DEG C ~ 50 DEG C; pyridine carboxylic acid ester and chiral sulfenamide react 1-12 hour under alkali effect; obtained optically active N-(sulfinyl) picolinamide
The mol ratio of described pyridine carboxylic acid ester, chiral sulfenamide and alkali is: (1-3): (0.01-0.5): (0.05-5);
The structural formula of described pyridine carboxylic acid ester is:
wherein, R 1be selected from C arbitrarily 1-C 16alkyl, C 4-C 10the heterocyclic radical containing N, O or sulphur or C 4-C 10heteroaryl, aryl containing N, O or sulphur, R 4be selected from C arbitrarily 1-C 16alkyl, C 4-C 10the heterocyclic radical containing N, O or sulphur or C 4-C 10heteroaryl, aryl containing N, O or sulphur; Described pyridine carboxylic acid ester obtains by after pyridine acid and analogue esterification thereof;
The structural formula of described chiral sulfenamide is: wherein * is chiral sulfur atom, R 2be selected from C arbitrarily 1-C 16alkyl or aryl;
Described alkali is alkalimetal hydride, alkaline earth metal hydride, lithium alkylide or lithium aryl.
3. the synthetic method of a kind of chirality nitrogen-sulphur bitooth ligand according to claim 2, it is characterized in that, described organic solvent is selected from benzene, tetracol phenixin, trichloromethane, methylene dichloride, tetrahydrofuran (THF), DMF, ether, dioxane or acetonitrile a kind of.
4. the synthetic method of a kind of chirality nitrogen-sulphur bitooth ligand according to claim 2; it is characterized in that, obtained optically active N-(sulfinyl) picolinamide is separated through the method for recrystallization, thin-layer chromatography, column chromatography or underpressure distillation.
5. an application for chirality nitrogen-sulphur bitooth ligand as claimed in claim 1, is characterized in that, described chirality nitrogen-sulphur bitooth ligand is applied in the asymmetric allylation of palladium chtalyst.
6. the application of a kind of chirality nitrogen-sulphur bitooth ligand according to claim 5, it is characterized in that, described chirality nitrogen-sulphur bitooth ligand is for the synthesis of optically active (E)-2-(1,3-diaryl allyl group)-2-fluoromalonic acid dimethyl ester compound; Synthetic method is as follows:
In organic solvent, at-78 DEG C ~ 50 DEG C, with allyl acetic acid ester compound and fluoromalonic acid dimethyl ester for raw material, with [Pd (C 3h 5) Cl] 2combine with chirality nitrogen-sulphur bitooth ligand, under the effect of additive, react 2-48 hour obtained optically active (E)-2-(1,3-diaryl allyl group)-2-fluoromalonic acid dimethyl ester compound.
Described allyl acetic acid ester compound, fluoromalonic acid dimethyl ester, [Pd (C 3h 5) Cl] 2, chirality nitrogen-sulphur bitooth ligand and additive mol ratio be (1-3): (0.01-5): (0.02-0.1): (0.05-5): (0.05-5);
The structural formula of described allyl acetic acid ester compound is: be selected from C arbitrarily 1-C 16alkyl, C 4-C 10the heterocyclic radical containing N, O or sulphur or C 4-C 10heteroaryl, aryl containing N, O or sulphur;
The structural formula of described fluoromalonic acid dimethyl ester is:
Described additive is selected from one or more in cesium carbonate, potassium acetate, cesium fluoride, cesium chloride, lithium chloride or tetra-n-butyl Neutral ammonium fluoride.
7. the application of a kind of chirality nitrogen-sulphur bitooth ligand according to claim 6, it is characterized in that, described optically active (E)-2-(1,3-diaryl allyl group)-2-fluoromalonic acid dimethyl ester compound is the optical pure compound with following structural formula
wherein * is chiral carbon atom, R 3be selected from C arbitrarily 1-C 16alkyl, C 4-C 10the heterocyclic radical containing N, O or sulphur or C 4-C 10heteroaryl, aryl containing N, O or sulphur.
8. the application of a kind of chirality nitrogen-sulphur bitooth ligand according to claim 6, it is characterized in that, described organic solvent is selected from benzene, tetracol phenixin, trichloromethane, methylene dichloride, tetrahydrofuran (THF), DMF, ether, dioxane or acetonitrile a kind of.
9. the application of a kind of chirality nitrogen-sulphur bitooth ligand according to claim 6, it is characterized in that, obtained optically active (E)-2-(1,3-diaryl allyl group)-2-fluoromalonic acid dimethyl ester compound is separated through the method for recrystallization, thin-layer chromatography, column chromatography or underpressure distillation.
10. the application of a kind of chirality nitrogen-sulphur bitooth ligand according to claim 9, it is characterized in that, during method with thin-layer chromatography or column chromatography, developping agent used is the mixed solvent of non-polar solvent and polar solvent, its volume ratio is, non-polar solvent: polar solvent=100-20:1;
Developping agent used is specifically selected from sherwood oil-methylene dichloride mixed solvent, petroleum ether-ethyl acetate mixed solvent or sherwood oil-ether mixed solvent.
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CN109851634A (en) * 2018-12-25 2019-06-07 华东师范大学 The preparation method and application of chiral monophosphorus ligand Yu-Phos and its full configuration
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CN109666043B (en) * 2018-12-25 2021-05-07 华东师范大学 Chiral monophosphine ligand CF-Phos with pyridine skeleton and preparation method and application thereof
CN115108874A (en) * 2021-03-18 2022-09-27 中国科学院福建物质结构研究所 Amine azide chiral compound, bis-azide chiral compound and related preparation methods
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