CN104926720B - A kind of chiral nitrogen sulphur bidentate ligand and its synthetic method and application - Google Patents
A kind of chiral nitrogen sulphur bidentate ligand and its synthetic method and application Download PDFInfo
- Publication number
- CN104926720B CN104926720B CN201410100202.3A CN201410100202A CN104926720B CN 104926720 B CN104926720 B CN 104926720B CN 201410100202 A CN201410100202 A CN 201410100202A CN 104926720 B CN104926720 B CN 104926720B
- Authority
- CN
- China
- Prior art keywords
- chiral
- bidentate ligand
- sulphur
- chiral nitrogen
- sulphur bidentate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 0 *CC1[C@@](*)CC[C@@]2[C@]1*C2 Chemical compound *CC1[C@@](*)CC[C@@]2[C@]1*C2 0.000 description 3
Landscapes
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The present invention relates to a kind of chiral nitrogen sulphur bidentate ligand and its synthetic method and application, first carboxylic acid is esterified, then reacted with chiral sulfenamide, it can obtain chiral nitrogen sulphur bidentate ligand, such part is combined with transition metal palladium, substrate is done with symmetrical allyl acetic acid ester, dimethyl malenate and fluoromalonic acid dimethyl ester are nucleopilic reagent, have successfully constructed chiral carbon-carbon bond.Compared with prior art, chiral nitrogen sulphur bidentate ligand synthesis material of the invention is easy to get, and synthetic method is simple；Chiral nitrogen sulphur bidentate ligand produced by the present invention is optically active N (sulfinyl) picolinamide; the chiral carbon-carbon bond for being applied to transition metal palladium chtalyst is constructed; reaction condition is gentle; it is easy to operate; the yield reacted in addition also preferably (generally 78% 99%), enantioselectivity height (highest 93%).
Description
Technical field
The present invention relates to a kind of chiral nitrogen-sulphur bidentate ligand and its synthetic method and application, belongs to chipal compounds synthesis
Field.
Background technology
Chirality is a kind of universal natural phenomena, the hand of spiral of galaxy greatly into universe, small functions different into molecule
The arrangement mode of group, it is all relevant with chirality.Many physiological activities have a participation of chiral material in organism, and chemical composition is identical
And chiral different similar substance, into organism in may have completely different effect.By taking " reaction stops " event as an example, connection
Bond state pharmaceutical factory is put into compound Thalidomide (Thalidomide) as anti-pregnant medicine in European market, later hair
Now the medicine has strong teratogenesis to ewborn infant, and research shows, chiral C-N keys are contained in Thalidomide molecules, throws
It is racemic compound to enter the medicine in market, and R- (+) structure has maincenter sedation, the mapping of another configuration S- (-)
Body then has strong teratogenesis, and therefore, contained chiral factor causes the extensive attention of people in organic molecule, 1992
U.S. FDA formally discloses the chiral drug code administration guide of entitled " new alloisomerism drug development statement of the policy " first,
Subsequent European Union also disclosed the file of " chiral material research " in 1994.
For organic chemist, after the importance of chirality is recognized, synthesizing single optically pure compound turns into
One important research direction.Chiral material how is obtained, generally there is natural products derivatization, raceme chiral resolution, micro- life
Thing is catalyzed, the several method such as enzymatic and asymmetric syntheses.Wherein, dissymmetric synthesis has been successfully applied to industrial metaplasia
Production.Chemist Noyori, Sharpless, Knowles obtain 2001 due to the contribution in terms of asymmetric hydrogenation and oxidation
Year 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 described above, the asymmetric syntheses of organic matter is realized by metal catalytic, it is necessary to which construction is chiral during the course of the reaction
Environment, chiral ligand just play a part of forming chiral environment.From starting till now, chemist has synthesized various for asymmetric syntheses
The monodentate of configuration, bidentate and multiple tooth chiral ligand, suitable for different types of asymmetric catalysis synthesis.Nevertheless, in view of have
The complexity of machine reaction, does not find a kind of part with general applicability also currently, it means that the hand to having no report
The exploratory development of property part will continue.
The content of the invention
It is an object of the present invention to overcome the above-mentioned drawbacks of the prior art and provide a kind of chiral nitrogen-sulphur bidentate
Part and its synthetic method and application.
The purpose of the present invention can be achieved through the following technical solutions：
A kind of chiral nitrogen-sulphur bidentate ligand, specially optically active N- (sulfinyl) picolinamide, there is following knot
Structure formula：
Wherein * is chiral sulfur atom, R1Arbitrarily it is selected from C1-C16Alkyl, C4-C10Contain N, O
Or the heterocyclic radical or C of sulphur4-C10The heteroaryl containing N, O or sulphur, aryl；R2Arbitrarily it is selected from C1-C16Alkyl or aryl.
A kind of synthetic method of chiral nitrogen-sulphur bidentate ligand, in organic solvent, at -78 DEG C~50 DEG C, picolinic acid ester
1-12 hours are reacted under alkali effect with chiral sulfenamide, optically active N- (sulfinyl) picolinamide is made,
The mol ratio of described picolinic acid ester, chiral sulfenamide and alkali is：(1-3)∶(0.01-0.5)∶(0.05-
5)：
The structural formula of described picolinic acid ester is：
Wherein, R1Arbitrarily it is selected from C1-C16Alkyl, C4-C10Heterocyclic radical containing N, O or sulphur or
Person C4-C10The heteroaryl containing N, O or sulphur, aryl, R4Arbitrarily it is selected from C1-C16Alkyl, C4-C10The heterocycle containing N, O or sulphur
Base or C4-C10The heteroaryl containing N, O or sulphur, aryl；After described picolinic acid ester is esterified by pyridine acid and the like
Obtain；
The structural formula of described chiral sulfenamide is：Wherein * is chiral sulfur atom, R2Arbitrarily it is selected from C1-
C16Alkyl or aryl；
Described alkali is alkali metal hydride, alkaline earth metal hydride, lithium alkylide or aryl lithium.
Described organic solvent is selected from benzene, carbon tetrachloride, chloroform, dichloromethane, tetrahydrofuran, N, N- dimethyl methyls
It is a kind of in acid amides, ether, dioxane or acetonitrile.
The specific reaction equation of N- (sulfinyl) picolinamide of synthesizing optical activity is as follows：
Wherein, base is described various alkali, and solvent is described organic solvent.
Obtained optically active N- (sulfinyl) picolinamide is by recrystallization, thin-layer chromatography, column chromatography or decompression
The method of distillation separates.
With thin-layer chromatography, column chromatography method when, solvent used is the mixed solvent of non-polar solven and polar solvent.
It can be petroleum ether-dichloromethane to recommend solvent, petroleum ether-ethyl acetate, and the mixed solvent such as petroleum ether-ether, its volume ratio can
To be respectively：Non-polar solven：Polar solvent=100-20: 1.Such as：Petrol ether/ethyl acetate=100-20/1, petroleum ether/
Dichloromethane=100-20/1.
A kind of application of chiral nitrogen-sulphur bidentate ligand, described chiral nitrogen-sulphur bidentate ligand are applied to the not right of palladium chtalyst
Claim in allylation reaction, specifically for (E) -2- (1,3- diaryl pi-allyl) -2- fluoromalonic acids of synthesizing optical activity
Dimethyl ester compound；Synthetic method is as follows：In organic solvent, at -78 DEG C~50 DEG C, preferably -20 DEG C of reaction temperature~
At 50 DEG C, using allyl acetic acid ester type compound and fluoromalonic acid dimethyl ester as raw material, with [Pd (C3H5)Cl]2With chiral nitrogen-
Sulphur bidentate ligand is combined, in the presence of additive react 2-48 hours optically active (E) -2- (1,3- diaryl is made
Pi-allyl) -2- fluoromalonic acid dimethyl ester compounds.
Described allyl acetic acid ester type compound, fluoromalonic acid dimethyl ester, [Pd (C3H5)Cl]2, chiral nitrogen-sulphur it is double
The mol ratio of tooth part and additive is (1-3): (0.01-5): (0.02-0.1): (0.05-5): (0.05-5)；Reaction rubs
That ratio preferably 1: 3: 0.O1: 0.01: 3: 3.
The structural formula of described allyl acetic acid ester type compound is：Arbitrarily it is selected from C1-C16Alkane
Base, C4-C10The heterocyclic radical or C containing N, O or sulphur4-C10The heteroaryl containing N, O or sulphur, aryl；
The structural formula of described fluoromalonic acid dimethyl ester is：
Described additive is in cesium carbonate, potassium acetate, cesium fluoride, cesium chloride, lithium chloride or tetra-n-butyl ammonium fluoride
One or more.
Described optically active (E) -2- (1,3- diaryl pi-allyl) -2- fluoromalonic acid dimethyl ester compounds are
Optical pure compound with following structural formula,
Wherein * is asymmetric carbon atom, R3Arbitrarily it is selected from C1-C16Alkyl, C4-C10Containing N, O or
The heterocyclic radical or C of sulphur4-C10The heteroaryl containing N, O or sulphur, aryl.
Described organic solvent is selected from benzene, carbon tetrachloride, chloroform, dichloromethane, tetrahydrofuran, N, N- dimethyl
It is a kind of in formamide, ether, dioxane or acetonitrile.
(E) -2- (1,3- diaryl pi-allyl) -2- fluoromalonic acid dimethyl ester compounds of synthesizing optical activity are specific
Reaction equation is as follows：
Wherein, L is optically active N- (sulfinyl) picolinamide, addictive be described various additives or
Combination, solvent is described organic solvent.
Obtained optically active (E) -2- (1,3- diaryl pi-allyl) -2- fluoromalonic acid dimethyl esters compound warp
Recrystallization, thin-layer chromatography, column chromatography or the method for vacuum distillation are crossed to separate.
With thin-layer chromatography, column chromatography method when, solvent used is the mixed solvent of non-polar solven and polar solvent.
It can be petroleum ether-dichloromethane to recommend solvent, petroleum ether-ethyl acetate, and the mixed solvent such as petroleum ether-ether, its volume ratio can
To be respectively：Non-polar solven：Polar solvent=100-20: 1.Such as：Petrol ether/ethyl acetate=100-20/1, petroleum ether/
Dichloromethane=100-20/1.
Compared with prior art, the present invention has advantages below and beneficial effect：
(1) chiral nitrogen-sulphur bidentate ligand synthesis material of the invention is easy to get, and synthetic method is simple；
(2) chiral nitrogen produced by the present invention-sulphur bidentate ligand is optically active N- (sulfinyl) picolinamide, by it
Chiral carbon-carbon bond applied to transition metal palladium chtalyst is constructed, and reaction condition is gentle, easy to operate, the yield reacted in addition
Preferably (generally 78%-99%), enantioselectivity height (highest 93%).
Embodiment
With reference to specific embodiment, the present invention is described in detail.
Embodiment 1
The synthesis of chiral nitrogen-sulphur bidentate ligand
Compound 1 (pyridine -2,6- dioctyl phthalate, 5.0g, 30.O mmol) and 10mL methanol are added in 100mL egg type bottles,
The 10mL concentrated sulfuric acids are instilled, are heated to reflux.After stopping reaction, sodium carbonate and sulfuric acid reaction are added, when solution is in neutral, DCM extractions
Take 3 times, saturated common salt is washed 1 time, adds anhydrous sodium sulfate drying.Filter, be spin-dried for organic solvent and obtain compound 1a.
By compound 1a (4.0g, 20.5mmol), 30mL methanol and 20mL dichloromethane are added in 250mL there-necked flasks, are added
Enter NaBH4(0.86g, 22.4mmol), stirring reaction.After stopping reaction, solvent is spin-dried for, post separation is crossed, obtains compound 2a.
NaH (0.36g, 15.0mmol) and 20mL tetrahydrofurans are added in reaction tube, suspension is stirred into, by compound
2a (2.0g, 12.0mmol) is added in reaction tube, after stirring 1 hour, adds allyl bromide, bromoallylene (1.8g, 15.0mmol), reaction knot
Shu Hou, solid is filtered, rotary evaporation falls solvent, crosses post separation, obtains compound 3f.
By (R)-t-butyl sulfonamide (0.30g, 2.5mmol), KH (0.10g, 2.5mmol) and 15mL tetrahydrofurans add
Enter in reaction tube, stirring reaction 1 hour, add compound 3f (0.52g, 2.5mmol), after reaction terminates, filter, be spin-dried for, mistake
Post separation, obtain compound 4f.
Embodiment 2~19
The research of the additive of palladium chtalyst asymmetry allyl reaction, solvent and part
Wherein mol refers to mole, and Base refers to alkali, and Solvent refers to solvent, Ligand assignment bodies, and Time refers to the time, and equiv. refers to
Equivalent, ee refer to percent enantiomeric excess.
In the reaction tube for the argon gas protection that one dries, 4.0mol% [Pd (C are sequentially added3H5)Cl]2, 8.0mol% matches somebody with somebody
Body, it is stirred at room temperature 30 minutes, then adds 1.0equiv.5a (0.2mmol), continue stirring 10 minutes, simultaneously will
3.0equiv.6a (1.5mmol) and 3.0equiv. Base is stirred in another by-reaction pipe in 1.5Solvent solvents
Pre-prepared nucleopilic reagent is reacted, nucleopilic reagent is added in catalyst, stirring reaction.After reaction terminates, after removal of solvent under reduced pressure
Residue thin-layer chromatography obtains target product (petroleum ether/dichloromethane=1/1, or petrol ether/ethyl acetate=10/1, v/
v)。
Different ligands are as follows：
Different ligands, organic solvent, alkali and under the reaction time, obtained product 7a situation such as table1It is shown,
Table 1
The ingredient proportion that [a] reacts in various solvents is：4.0mol% [Pd (C3H5)Cl]2, 8.0mol%ligand,
1.0equiv.5a (0.2mmol), 3.0equiv.6a (1.5mmol) and 3.0equiv. Base in 2.5mLSolvent in
React at room temperature.
[b] refers to separation yield.
[c] refers in embodiment 17, with Pd (dba)2Substitute [Pd (C3H5)Cl]2As catalyst.
[d] refers in embodiment 18, and organic solvent is 3.0equiv.of BSA (N, O-Bis (trimethylsilyl)
Acetamide, 0.6mmo1) and 4mol% KOAc.
[e] refers in embodiment 19, and organic solvent is 3.0equiv.of BSA (N, O-Bis (trimethylsilyl)
Acetamide, 0.6mmol) and 4mol% NaOAc.
[f] refers to percent enantiomeric excess (ee) and determined by Chiral liquid chromatography.
Wherein：Solvent DCM is dichloromethane, and PhMe is toluene, and THF is tetrahydrofuran；Trace, which refers to, a small amount of product.
Embodiment 20~30
The asymmetric allyl reaction applicability 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 time, Ligand assignment body (compounds
4f), equiv. refers to equivalent.
In the reaction tube for the argon gas protection that one dries, 4.0mol% [Pd (C are sequentially added3H5)Cl]2, 8.0mol% matches somebody with somebody
Body, it is stirred at room temperature 30 minutes, then adds 1.0equiv.5 (0.2mmol), continue stirring 10 minutes, by 3.0equiv.8
(1.5mmol) and 3.0equiv. Base (1.5mmol) are added in reaction tube, stirring reaction.After reaction terminates, it is removed under reduced pressure
Residue thin-layer chromatography obtains target product (petroleum ether/dichloromethane=1/1, or petrol ether/ethyl acetate=10/ after solvent
1, v/v).
Wherein：Solvent DCM is dichloromethane, and PhMe is toluene, and THF is tetrahydrofuran；Trace, which refers to, a small amount of product.
Different ligands, organic solvent, alkali and under starting compound 5, reaction time, the situation such as institute of table 1 of obtained product 9
Show,
Table 2
The ingredient proportion that [a] reacts in various solvents is：4.0mol% [Pd (C3H5)Cl]2, 8.0mol%ligand,
1.0equiv.5 (0.2mmol), 3.0equiv.8 (1.5mmol) and 3.0equiv. Cs2CO3In room temperature in 2.5mL solvents
Lower reaction.
[b] refers to the separation yield of compound 9.
[c] refers to percent enantiomeric excess (ee) and determined by Chiral liquid chromatography.
[d], which refers to be used as with (S, S)-DACH-naphthyl Trost Ligand alternative compounds 4f in embodiment 22, to be matched somebody with somebody
Body.
Embodiment related products physical property characterizes and yield is as follows：
P1：6- (allyl methoxyl) pyridine carboxylic acid methyl esters
Weak yellow liquid, 56% yield.
1H NMR (400MHz, CDCl3) 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, CDCl3) 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 C11H13NNaO3([M+Na]+)：230.0793, Found：230.0788.
IR(KBr)：vmax(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, CDCl3) 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, CDCl3) 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 C27H23NNaO3([M+Na]+)：432.1576, Found：432.1570.
IR(KBr)：vmax(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 ° of (c1.0, CHCl3)。
1H NMR (400MHz, CDCl3) 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, CDCl3) δ=164.2,148.1,147.4,137.4,127.2,122.3,56.3,21.6.
HRMS(ESI)calcd for C10H14N2NaO2S([M+Na]+)：249.0647, Found：249.0598.
IR(KBr)：vmax(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 ° of (c1.0, CHCl3).1H NMR (400MHz, CDCl3) 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, CDCl3) 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 C14H16N2NaO2S([M+Na]+)：299.0830
Found：299.0769.
IR(KBr)：vmax(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) isoquinolin -1- carboxylic acid amides
White solid, 43% yield.
m.p.61.4-64.6℃。
[α]D 20- 312.0 ° of (c1.0, CHCl3).1H NMR (400MHz, CDCl3) 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, CDCl3) 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 C14H16N2NaO2S([M+Na]+)：299.0830, Found：299.0824.
IR(KBr)：vmax(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 ° of (c0.9, CHCl3).1H NMR (400MHz, CDCl3) 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, CDCl3) δ=164.9,157.7,147.4,137.8,127.2,120.0,57.0,24.2,
22.1。
HRMS(ESI)calcd for C11H16N2NaO2S([M+Na]+)：263.0830, Found：263.0825.
IR(KBr)：vmax(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 ° of (c0.5, CHCl3).1H NMR (400MHz, CDCl3) 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, CDCl3) 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 C11H16N2NaO3S([M+Na]+)：325.0987, Found：325.0981.
IR(KBr)：vmax(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 ° of (c1.0, CHCl3)。
1H NMR (400MHz, CDCl3) 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, CDCl3) 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 C14H20N2NaO3S([M+Na]+)：319.1092, Found：319.1084.
IR(KBr)：vmax(cm-1)=3901,3853,3801,3747,3649,1734,1700,1685,1651,1472,
1395,1361,1261,1072,829,752,595.
P9：(R) -6- (benzyl group methoxyl group)-N- (terf-butylsulfinyl) picolinamide
White solid, 39% yield.
m.p.86.5-87.8℃。
[α]D 20- 289.6 ° of (c0.7, CHCl3).1H NMR (400MHz, CDCl3) 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, CDCl3) 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 C18H22N2NaO3S([M+Na]+)：369.1249, Found：369.1244.
IR(KBr)：vmax(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 methoxies base)) picolinamide
Thick liquid, 26% yield.
[α]D 20- 18.5 ° of (c3.0, CHCl3)。
1H NMR (400MHz, CDCl3) 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, CDCl3) 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 C22H24N2NaO3S([M+Na]+)：419.1405, Found：419.1411.
IR(KBr)：vmax(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 ° of (c1.0, CHCl3)。
1H NMR (400MHz, CDCl3) 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, CDCl3) 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 C30H30N2NaO3S([M+Na]+)：521.1875, Found：521.1870.
IR(KBr)：vmax(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 ° of (c2.0, CHCl3)。
1H NMR (400MHz, CDCl3) 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, CDCl3) 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 C14H18N2NaO3S([M+Na]+)：317.0936, Found：317.0926.
IR(KBr)：vmax(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 ° of (c1.0, CHCl3)。
1H NMR (400MHz, CDCl3) 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, CDCl3) δ=172.6,167.2,132.3,128.5,126.4,69.7,69.1,
56.9.22.0。
HRMS(ESI)calcd for C14H18N2NaO3S([M+Na]+)：317.0936, Found： 317.0923.
IR(KBr)：vmax(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 ° of (c1.0, CHCl3)。
1H NMR (400MHz, CDCl3) 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, CDCl3) δ=172.5,172.2,132.1,132.0,128.6,128.3,79.356.9,
34.7 22.0.
HRMS(ESI)calcd for C14H18N2NaO2S2([M+Na]+)：333.0707, Found：333.0700.
IR(KBr)：vmax(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 ° of (c0.9, CHCl3)。
1H NMR (400MHz, CDCl3) 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, CDCl3) 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 C14H18N2NaO2S2([M+Na]+)：333.0707, Found：333.0705.
IR(KBr)：vmax(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 ° of (c2.0, CHCl3)。
1H NMR (400MHz, CDCl3) 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, CDCl3) δ=169.2,138.7 (d, JC-P=25.5Hz), 136.1 (ddd, JC-P=
21.2,11.7,9.5Hz), 134.4,133.8 (d, JC-P=19.7Hz), 133.6 (d, JC-P=19.6Hz), 131.2,130.0,
128.9,128.8 (d, JC-P=5.1Hz), 128.6 (dd, JC-P=7.3,6.6Hz), 57.3,22.0.
31P NMR (162MHz, CDCl3) δ=- 10.40.
HRMS(ESI)calcd for C23H24NqaO2PS([M+Na]+)：432.1163, Found：432.1152.
IR(KBr)：vmax(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- bases) pi-allyl) -2- fluoromalonic acid dimethyl esters
White solid, 78% yield, 80%ee [Diacel CHIRALPAK AD-H (0.46cmx25cm)；N-hexane/different
Propyl alcohol=80/20, flow velocity=0.8mL/min, Detection wavelength=214nm；tR=9.80min (minor), 23.02min
(major)]。
m.p.106.3-108.2℃。
[α]D 20- 63.6 ° of (c3.0, CHCl3)。
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, CDCl3) δ=166.1 (d, JC-F=25.7Hz), 165.1 (d, JC-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 .JC-F=
210.3Hz), 53.6,53.0,47.6 (d, JC-F=18.4Hz).
HRMS(ESI)calcd for C28H23FNa04([M+Na]+)：465.1478, Found：465.1482.
IR(KBr)：vmax(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 esters
White solid, 83% yield, 77%ee [Diacel CHIRALPAK AD-H (0.46cm x25cm)；N-hexane/
Isopropanol=80/20, flow velocity=0.8mL/min, Detection wavelength=254nm；tR=9.98min (major), 11.28min
(minor)]。
m.p.97.7-99.4℃。
[α]D 20+ 45.0 ° of (c2.0, CHCl3)。
1H NMR (400MHz, CDCl3) 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, CDCl3) δ=165.6 (d, JC-F=25.7Hz), 165.2 (d, JC-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, JC-F=210.3Hz), 53.8 (d, JC-F=18.3Hz), 53.4,53.0,21.4,
21.2。
HRMS(ESI)calcd for C22H23FNaO4([M+Na]+)：393.1478, Found：393.1473.
IR(KBr)：vmax(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- to benzyl pi-allyl) -2- fluoromalonic acid dimethyl esters
White solid, 69% yield, 80%ee [Diacel CHIRALPAK AD-H (0.46cm x25cm)；N-hexane/
Isopropanol=80/20, flow velocity=0.8mL/mi n, Detection wavelength=254nm；tR=14.63min (major), 15.76min
(minor)]。
m.p.83.9-84.8℃。
[α]D 20+ 66.8 ° of (c1.0, CHCl3)。
1H NMR (400MHz, CDCl3) 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, CDCl3) δ=- 176.00.
13C NMR (100MHz, CDCl3) δ=165.7 (d, JC-F=25.5Hz), 165.2 (d, JC-F=26.2Hz),
137.6,137.4,133.9,133.74,133.69,129.3,129.1,128.9,126.4,123.7 (d, JC-F=2.9Hz),
97.6 (d, JC-F=208.0Hz), 53.5 (d, JC-F=18.2Hz), 53.4,53.1,21.1,21.0.
HRMS(ESI)calcd for C22H23FNaO4([M+Na]+)：393.1478, Found：393.1477.
IR(KBr)：vmax(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- bromophenyls) pi-allyl) -2- fluoromalonic acid dimethyl esters
White solid, 99% yield, 90%ee [Diacel CHIRALPAK AD-H (0.46cm x25cm)；N-hexane/
Isopropanol=80/20, flow velocity=0.8mL/min, Detection wavelength=254nm；tR=12.93min (minor), 13.94min
(major)]。
m.p.93.9-95.4℃。
[α]D 20+ 63.5 ° of (c2.0, CHCl3)。
1H NMR (400MHz, CDCl3) 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, CDCl3) δ=- 175.46.
13C NMR (100MHz, CDCl3) δ=165.2 (d, JC-F=25.5Hz), 164.8 (d, JC-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, JC-F=
4.4Hz), 125.2,122.7,122.6,98.5 (d, JC-F=208.7Hz), 53.7,53.4,53.1 (d, JC-F=18.3Hz).
HRMS(ESI)calcd for C20H17Br2FNaO4([M+Na]+)：520.9375, Found：520.9370.
IR(KBr)：vmax(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- fluorophenyls) pi-allyl) -2- fluoromalonic acid dimethyl esters
White solid, 93% yield, 90%ee [Diacel CHIRALPAK AD-H (0.46cm x25cm)；N-hexane/
Isopropanol=80/20, flow velocity=0.8mL/min, Detection wavelength=254nm；tR=13.83min (major), 15.31min
(minor)]。
m.p.90.7-92.1℃。
[α]D 20+ 63.5 ° of (c2.0, CHCl3)。
1H NMR (400MHz, CDCl3) 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, CDCl3) δ=- 176.00, -114.17, -113.65.
13C NMR (126MHz, CDCl3) δ=165.5 (d, JC-F=25.7Hz), 165.0 (d, JC-F=25.7Hz),
162.5 (d, JC-F=248.0Hz), 162.3 (d, JC-F=247.8Hz), 133.2,132.4 (dd, JC-F=7.4,3.8Hz),
130.7 (dd, JC-F=8.3,2.8Hz), 128.1,128.0,127.2,115.5 (d, JC-F=21.2Hz), 115.4 (d, JC-F=
22.0Hz), 97.4 (d, JC-F=210.3Hz), 53.5,53.2,52.9 (d, JC-F=18.3Hz).
HRMS(ESI)calcd for C20H17F3NaO4([M+Na]+)：230.0793, Found：230.0788.
IR(KBr)：vmax(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- chlorphenyls) pi-allyl) -2- fluoromalonic acid dimethyl esters
White solid, 88% yield, 90%ee [Diacel CHIRALPAK AD-H (0.46cm x25cm)；N-hexane/
Isopropanol=80/20, flow velocity=0.8mL/min, Detection wavelength=254nm；tR=18.06min (major), 20.81min
(minor)]。
m.p.103.7-105.5℃。
[α]D 20+ 69.7 ° of (c2.0, CHCl3)。
1H NMR (400MHz, CDCl3) 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, CDCl3) δ=- 175.70.
13C NMR (126MHz, CDCl3) δ=165.3 (d, JC-F=25.7Hz), 164.9 (d, JC-F=25.7Hz),
135.0,134.7,133.8,133.7,133.3,130.4,128.8,128.7,127.7,124.8 (d, JC-F=3.6Hz),
97.1 (d, JC-F=210.3Hz), 53.5,53.3,53.0 (d, JC-F=18.2Hz).
HRMS(ESI)calcd for C20H17C12FNaO4([M+Na]+)：433.0386, Found：433.0380.
IR(KBr)：Vmax(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- bromophenyls) pi-allyl) -2- fluoromalonic acid dimethyl esters
White solid, 86% yield, 91%ee [Diacel CHIRALPAK AD-H (0.46cm x25cm)；N-hexane/
Isopropanol=80/20, flow velocity=0.8mL/min, Detection wavelength=254nm；tR=21.86min (major), 26.72min
(minor)]。
m.p.71.0-72.6℃。
[α]D 20+ 30.9 (c3.0, CHCl3)。
1H NMR (400MHz, CDCl3) 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, CDCl3) δ=- 175.70.
13C NMR (100MHz, CDCl3) δ=165.2 (d, JC-F=25.6Hz), 164.8 (d, JC-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, JC-F=
208.7Hz), 53.5,53.3,53.0 (d, JC-F=18.2Hz).
HRMS(ESI)calcd for C20H17Br2FNaO4([M+Na]+)：520.9375, Found：520.9375.
IR(KBr)：vmax(cm-1)=3853,3747,3673,3477,1759,1716,1699,1650,1617,
1558.1541,1487,1254,1140,1072,1010,969,848,799,766,721,612.
The above-mentioned description to embodiment is understood that for ease of those skilled in the art and using invention.
Person skilled in the art obviously can easily make various modifications to these embodiments, and described herein general
Principle is applied in other embodiment without by performing creative labour.Therefore, the invention is not restricted to above-described embodiment, ability
Field technique personnel do not depart from improvement that scope made and modification all should be in the present invention according to the announcement of the present invention
Protection domain within.
Claims (10)
- A kind of 1. chiral nitrogen-sulphur bidentate ligand, it is characterised in that it is specially optically active N- (sulfinyl) picolinamide, With following structural formula：Wherein * is chiral sulfur atom, R1Selected from H, CH3Or phenyl；R2Selected from the tert-butyl group.
- 2. a kind of synthetic method of chiral nitrogen-sulphur bidentate ligand as claimed in claim 1, it is characterised in that in organic solvent In, at -78 DEG C~50 DEG C, picolinic acid ester reacts 1-12 hours with chiral sulfenamide under alkali effect, and optical activity is made N- (sulfinyl) picolinamide,The mol ratio of described picolinic acid ester, chiral sulfenamide and alkali is：(1-3):(0.01-0.5):(0.05-5)；The structural formula of described picolinic acid ester is：Wherein, R1Selected from H, CH3Or phenyl, R4Arbitrarily it is selected from C1-C16Alkyl, C4-C10Containing N, O or Heteroaryl, the aryl of sulphur；Described picolinic acid ester obtains after being esterified by pyridine acid and the like；The structural formula of described chiral sulfenamide is：Wherein * is chiral sulfur atom, R2Selected from the tert-butyl group；Described alkali is alkali metal hydride, alkaline earth metal hydride, lithium alkylide or aryl lithium.
- 3. the synthetic method of a kind of chiral nitrogen-sulphur bidentate ligand according to claim 2, it is characterised in that described has Solvent is selected from benzene, carbon tetrachloride, chloroform, dichloromethane, tetrahydrofuran, N,N-dimethylformamide, ether, dioxy six It is a kind of in ring or acetonitrile.
- A kind of 4. synthetic method of chiral nitrogen-sulphur bidentate ligand according to claim 2, it is characterised in that obtained light N- (sulfinyl) picolinamide for learning activity separates by recrystallization, thin-layer chromatography, column chromatography or the method for vacuum distillation.
- A kind of 5. application of chiral nitrogen-sulphur bidentate ligand as claimed in claim 1, it is characterised in that described chiral nitrogen-sulphur Bidentate ligand is applied in the asymmetric allylation of palladium chtalyst.
- A kind of 6. application of chiral nitrogen-sulphur bidentate ligand according to claim 5, it is characterised in that described chiral nitrogen- Sulphur bidentate ligand is used for (E) -2- (1,3- diaryl pi-allyl) -2- fluoromalonic acid dimethyl ester chemical combination of synthesizing optical activity Thing；Synthetic method is as follows：In organic solvent, at -78 DEG C~50 DEG C, using allyl acetic acid ester type compound and fluoromalonic acid dimethyl ester as original Material, with [Pd (C3H5)Cl]2It is combined with chiral nitrogen-sulphur bidentate ligand, 2-48 hours obtained light is reacted in the presence of additive Learn (E) -2- (1,3- diaryl pi-allyl) -2- fluoromalonic acid dimethyl ester compounds of activity；Described allyl acetic acid ester type compound, fluoromalonic acid dimethyl ester, [Pd (C3H5)Cl]2, chiral nitrogen-sulphur bidentate matches somebody with somebody The mol ratio of body and additive is (1-3):(0.01-5):(0.02-0.1):(0.05-5):(0.05-5)；The structural formula of described allyl acetic acid ester type compound is：R3Arbitrarily it is selected from C1-C16Alkyl, C4- C10The heterocyclic radical containing N, O or sulphur；The structural formula of described fluoromalonic acid dimethyl ester is：Described additive in cesium carbonate, potassium acetate, cesium fluoride, cesium chloride, lithium chloride or tetra-n-butyl ammonium fluoride one Kind is several.
- 7. the application of a kind of chiral nitrogen-sulphur bidentate ligand according to claim 6, it is characterised in that described optics is lived (E) -2- (1,3- diaryl pi-allyl) -2- fluoromalonic acid dimethyl esters compounds of property are the optics with following structural formula Pure compound,Wherein * is asymmetric carbon atom, R3Arbitrarily it is selected from C1-C16Alkyl, C4-C10Containing N, O or sulphur Heterocyclic radical.
- 8. the application of a kind of chiral nitrogen-sulphur bidentate ligand according to claim 6, it is characterised in that described is organic molten Agent be selected from benzene, carbon tetrachloride, chloroform, dichloromethane, tetrahydrofuran, N,N-dimethylformamide, ether, dioxane or It is a kind of in acetonitrile.
- 9. the application of a kind of chiral nitrogen-sulphur bidentate ligand according to claim 6, it is characterised in that obtained optics is lived Property (E) -2- (1,3- diaryl pi-allyl) -2- fluoromalonic acid dimethyl esters compound by recrystallization, thin-layer chromatography, post Chromatography or the method being evaporated under reduced pressure separate.
- A kind of 10. application of chiral nitrogen-sulphur bidentate ligand according to claim 9, it is characterised in that with thin-layer chromatography or During the method for column chromatography, solvent used is the mixed solvent of non-polar solven and polar solvent, and its volume ratio is, nonpolar molten Agent：Polar solvent=100-20：1；Solvent used is chosen in particular from petroleum ether-dichloromethane mixed solvent, petroleum ether-ethyl acetate mixed solvent or oil Ether-ether mixed solvent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410100202.3A CN104926720B (en) | 2014-03-18 | 2014-03-18 | A kind of chiral nitrogen sulphur bidentate ligand and its synthetic method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410100202.3A CN104926720B (en) | 2014-03-18 | 2014-03-18 | A kind of chiral nitrogen sulphur bidentate ligand and its synthetic method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104926720A CN104926720A (en) | 2015-09-23 |
| CN104926720B true CN104926720B (en) | 2018-02-09 |
Family
ID=54114178
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410100202.3A Expired - Fee Related CN104926720B (en) | 2014-03-18 | 2014-03-18 | A kind of chiral nitrogen sulphur bidentate ligand and its synthetic method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104926720B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105884682B (en) * | 2016-05-24 | 2018-10-19 | 合肥工业大学 | A kind of synthetic method of 2,6- pyridinedicarboxylic acids methyl esters crystal |
| CN106187836A (en) * | 2016-07-01 | 2016-12-07 | 成都理工大学 | Chirality N cinnamyl N phenyl t-butyl sulfenamide and preparation and application |
| CN106748917B (en) * | 2016-12-08 | 2018-07-06 | 同济大学 | A kind of chiral sulfenamide ligand and its preparation method and application |
| 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 |
| CN109851634B (en) * | 2018-12-25 | 2020-12-22 | 华东师范大学 | Chiral monophosphine ligand Yu-Phos and preparation method and application of full configuration thereof |
| CN115108874B (en) * | 2021-03-18 | 2023-09-08 | 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 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101538264A (en) * | 2008-03-19 | 2009-09-23 | 中国科学院成都有机化学有限公司 | Novel method for preparing chiral sulphoxide compound |
| WO2012155042A2 (en) * | 2011-05-11 | 2012-11-15 | Anderson Development Company | Novel borate derivatives and their applications |
| CN103012442A (en) * | 2012-12-25 | 2013-04-03 | 常州大学 | Cuprum (II) coordination compound catalyst of selective catalytic oxidation thioether and preparation method of cuprum (II) coordination compound catalyst |
-
2014
- 2014-03-18 CN CN201410100202.3A patent/CN104926720B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101538264A (en) * | 2008-03-19 | 2009-09-23 | 中国科学院成都有机化学有限公司 | Novel method for preparing chiral sulphoxide compound |
| WO2012155042A2 (en) * | 2011-05-11 | 2012-11-15 | Anderson Development Company | Novel borate derivatives and their applications |
| CN103012442A (en) * | 2012-12-25 | 2013-04-03 | 常州大学 | Cuprum (II) coordination compound catalyst of selective catalytic oxidation thioether and preparation method of cuprum (II) coordination compound catalyst |
Non-Patent Citations (5)
| Title |
|---|
| Chiral N-acyl-tert-butanesulfinamides: the "safety-catch" principle applied to diastereoselective enolate alkylations;Backes Bradley J. et al;《Journal of Organic Chemistry》;19990630;第64卷(第15期);第5472-5478页 * |
| Enantioselective Aza-Henry Reaction with an N-Sulfinyl Urea Organocatalyst;Robak MaryAnn T. et al;《Journal of the American Chemical Society》;20071231;第129卷(第49期);第15110-15111页 * |
| Highly enantioselective reduction of β-amino nitroolefins with a simple N-sulfinyl urea as bifunctional catalyst;Liu Xiang-Wei et al;《Chemistry - A European Journal》;20120626;第18卷(第30期);第9204-9207页 * |
| N-Sulfinylcarboximidates as a New Class of Chiral Bidentate Ligands: Application to Asymmetric Coordination Chemistry;Lin Zhijie et al;《Chemistry - A European Journal》;20110928;第17卷(第45期);第12602-12605页 * |
| 亚砜及亚磺酰胺类配体催化不对称反应的新进展;薛峰,等;《有机化学》;20131114;第34卷;第267-277页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104926720A (en) | 2015-09-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104926720B (en) | A kind of chiral nitrogen sulphur bidentate ligand and its synthetic method and application | |
| CN109311813B (en) | Palladium-catalyzed meta-C-H functionalized universal ligands | |
| CN110204486B (en) | Synthesis method of quinoline derivative | |
| CN107698586A (en) | It is a kind of that the method for preparing Pyridine-quinazolinocompound compound is catalyzed by copper compound | |
| CN101747318A (en) | 1-(3,5-dichloro-pyridyl)-1H-5-pyrazole carboxylic acid ester compound | |
| CN111423431A (en) | Preparation method of chlorantraniliprole and intermediate thereof | |
| JP2022508494A (en) | Method for Producing Morpholine Quinazoline Compound and its Intermediate | |
| CN111233852B (en) | NON type chiral bisoxazoline ligand and synthetic method and application thereof | |
| CN105085208B (en) | A kind of preparation method using palladium as catalyst benzfluorene ketone compounds | |
| CN107513003A (en) | A kind of preparation method of 1,4 2 substitution, 1,3 diacetylene | |
| CN105536873B (en) | A kind of composite catalyst and its application | |
| CN109776407B (en) | Preparation method of 2-methyl-4-hydroxymethyl quinoline and derivatives thereof | |
| CN107513056B (en) | A kind of synthetic method of the quinolines of the group containing tetrahydrofuran | |
| CN106588921B (en) | A kind of synthetic method of the methyl formate of 7 azaindole 3 | |
| CN106866511B (en) | A kind of preparation method of polysubstituted pyridine derivative | |
| CN110078766A (en) | Phosphonylation benzimidazole and compound of isobioquin group and preparation method thereof | |
| CN105820168B (en) | A kind of preparation method for replacing Buddhist nun's intermediate according to Shandong | |
| CN104558014B (en) | Chiral N-heterocyclic carbene precursor salt with 3,4-dihydroisoquinoline skeleton, synthetic method and application | |
| CN111100056A (en) | Synthetic method for preparing 3-thiophenyl indole compound by oxygen oxidation without transition metal catalysis | |
| CN106543081A (en) | A kind of preparation method of 1 fluoroalkyl isoquinolin | |
| CN103360343B (en) | Preparation method of piperazine amide compound | |
| CN117069711A (en) | Preparation method of benzoxazine-4-one derivative | |
| CN113072481A (en) | Indolo-cyclobutane skeleton compound, synthesis method and application | |
| CN105693778A (en) | N-methoxyl formamide-orientated method for synthesizing ferrocene and pyridone derivative | |
| CN107011218B (en) | A kind of fluorine nitrogen type amination reagent, preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20180209 Termination date: 20210318 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |