CN112898259B - Method for preparing 3-substituted chromanone through nonmetal catalytic hydrogenation - Google Patents
Method for preparing 3-substituted chromanone through nonmetal catalytic hydrogenation Download PDFInfo
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- CN112898259B CN112898259B CN201911218380.5A CN201911218380A CN112898259B CN 112898259 B CN112898259 B CN 112898259B CN 201911218380 A CN201911218380 A CN 201911218380A CN 112898259 B CN112898259 B CN 112898259B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/34—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 3 only
- C07D311/38—2,3-Dihydro derivatives, e.g. isoflavanones
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Abstract
The invention discloses a method for preparing 3-substituted chromanone through nonmetal catalytic hydrogenation. The method comprises the following steps: reacting a compound shown as a formula VI with hydrogen in a catalytic system of oxazoline shown as a formula I and borane shown as a formula II to obtain the catalyst. The invention takes various substituted chromone compounds (formula VI) as raw materials, and takes hydrogen as hydrogen source under the catalysis of oxazoline shown in formula I and borane shown in formula II to synthesize the 3-substituted chromanone compound (formula V) with high efficiency and high enantioselectivity. The method has the advantages of easy synthesis of the catalyst, mild reaction conditions, simple and convenient operation, high stereoselectivity and the like, the ee value of the product is as high as 95%, and the yield is as high as 98%.
Description
Technical Field
The invention relates to a method for preparing 3-substituted chromanone through nonmetal catalytic hydrogenation, belonging to the technical field of organic synthesis.
Background
The 3-substituted chromanone compound is a skeleton of a plurality of molecules with biological activity, for example, dihydrodaidzein has certain function of protecting cardiac muscle. At present, chiral metal catalysts are often needed for the preparation of the compounds, and a series of problems such as pollution and biological toxicity caused by metal residues are faced. Therefore, there is a need to provide a new method for preparing 3-substituted chromanone compounds without the need of metal catalyst catalysis.
Disclosure of Invention
The invention aims to provide a novel method for preparing a series of 3-substituted chromanone compounds with high efficiency and high enantioselectivity by using chiral hindered Lewis acid-base pairs as catalysts.
The invention adopts chiral oxazoline as base to match achiral borane to form hindered Lewis acid-base pairs (FLPs for short), uses 3-substituted chromone as raw material, adopts low-cost hydrogen as hydrogen source, obtains a series of 3-substituted chromone compounds with high efficiency and high enantioselectivity, and has certain potential application value.
The preparation method of the 3-substituted chiral chromanone compound shown in the formula V comprises the following steps:
reacting a compound shown as a formula VI with hydrogen in a catalytic system of oxazoline shown as a formula I and borane shown as a formula II to obtain the compound;
in the formulae VI and V, R1Represents a substituent on a benzene ring, and is H, alkyl with 1-6 carbon atoms, aryl with 6-7 carbon atoms or halogen; r2Is an alkyl group having 1 to 6 carbon atoms or an aryl group having 6 to 7 carbon atoms.
The oxazoline shown in the formula I adopted by the method is a chiral oxazoline Lewis base compound, and the structure of the oxazoline is shown as follows:
the oxazoline shown in the formula I can be prepared by a method comprising the following steps:
1) reacting a compound shown in a formula VII with a compound shown in a formula VIII in the presence of a base to obtain a corresponding amide compound;
2) then molybdenum ammonia acid (NH)4)6Mo7O24·4H2Reacting under the catalysis of O to obtain oxazoline shown in a formula I;
in the above method, in step 1), the molar ratio of the compound represented by formula II, the compound represented by formula III and the base may be 1: 1: 1.5.
the reaction was carried out in a two-neck round bottom flask, protected with nitrogen.
The reaction is carried out in an organic solvent, which may be specifically dichloromethane.
The reaction temperature can be room temperature, and the reaction time is 18-24 hours.
In order to ensure the uniformity of the reaction system, the reaction was carried out with stirring.
In the above method, in the step 2), the molar ratio of the amide compound to the molybdic acid is 1: 0.25.
the reaction is carried out in a two-mouth round-bottom flask, a water separator and a reflux condenser pipe are arranged, and nitrogen is used for protection.
The reaction is carried out in an organic solvent, which may be p-xylene.
The reaction temperature may be 145 ℃ for 24 hours.
In order to ensure the uniformity of the reaction system, the reaction was carried out with stirring.
The method further comprises the step of separating by column chromatography to obtain the oxazoline shown in the formula I.
In the column chromatography, the specification of the used chromatographic column is 30mm multiplied by 300mm (diameter multiplied by height); the column filler is silica gel (200-300 meshes); the eluent is a mixed solution of petroleum ether and ethyl acetate (volume ratio is 20: 1).
The borane adopted by the method disclosed by the invention is a chiral borane Lewis acid compound, and the structure of the borane is shown as follows:
the borane shown in the formula II can be prepared according to the method comprising the following steps:
reacting the compound shown in the formula III with isopropyl magnesium chloride in a glove box, stirring at room temperature for 2 hours, adding an ether solution of the compound shown in the formula IV, and stirring for 24 hours to obtain borane shown in the formula II;
in the above process, the molar ratio of the compound of formula III, isopropyl magnesium chloride and the compound of formula IV may be 2.25: 2.25: 1;
the reaction can be carried out in a two-neck round-bottom flask, protected with nitrogen in a glove box.
The reaction is carried out in an organic solvent, which may be diethyl ether.
In order to ensure the uniformity of the reaction system, the reaction was carried out with stirring.
The 3-substituted chiral chromanone compound shown as formula V prepared by the method, wherein R is1Specifically, the substituent group can be bromine, chlorine, methyl, phenyl, methyl-substituted phenyl, trifluoromethyl-substituted phenyl or methoxy-substituted phenyl; r2Specifically, the phenyl group can be methyl, ethyl, isopropyl or methyl substituted phenyl, and specifically, the following compounds can be used:
in the preparation method, the molar ratio of the oxazoline shown in the formula I, the borane shown in the formula II and the compound shown in the formula VI is 1: 1: 10-20, specifically 1: 1: 20.
in the preparation method, the reaction is carried out in an autoclave, and the pressure of the hydrogen is 40-60 bar, specifically 40 bar.
In the above preparation method, the reaction is carried out in an organic solvent; the organic solvent is mesitylene.
In the preparation method, the reaction temperature is 30-40 ℃ and the reaction time is 24-72 hours.
In the preparation method, after the reaction is finished, the method further comprises the step of separating and purifying the 3-substituted chiral chromanone compound shown in the formula V by column chromatography;
the column chromatography conditions were as follows:
the column filler is 200-300 meshes of silica gel; the eluent is: the volume ratio is 4: 1 of petroleum ether and dichloromethane.
The invention takes various substituted chromone compounds (formula VI) as raw materials, and takes hydrogen as hydrogen source under the catalysis of oxazoline shown in formula I and borane shown in formula II to synthesize the 3-substituted chromanone compound (formula V) with high efficiency and high enantioselectivity. The method has the advantages of easy synthesis of the catalyst, mild reaction conditions, simple and convenient operation, high stereoselectivity and the like, the ee value of the product is as high as 95%, and the yield is as high as 98%.
Detailed Description
The experimental procedures used in the following examples are all conventional procedures unless otherwise specified.
Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.
Example 1 preparation of the Compound of formula II
The reaction equation is as follows:
in a glove box, 2,3,5, 6-tetrafluorobromobenzene of formula III (5.253g,22.92mmol) was dissolved in 55mL of anhydrous diethyl ether at room temperature, isopropyl magnesium chloride (2M in diethyl ether, 11.46mL,22.92mmol) was slowly added dropwise, and the mixture was stirred at room temperature for 2 hours. This was added to a suspension of the compound represented by the formula IV in anhydrous ether (8mL), and the mixture was stirred at room temperature for 24 hours. The solution was drained and the solid residue was extracted three times with hot toluene (3X 20mL), filtered and the toluene was drained to give the crude product. The crude product was washed three times with n-hexane (3X 20mL), and the washed crude product was re-extracted three times with toluene (3X 20mL) and washed three times with n-hexane (3X 20mL) to give the borane of formula II.
The structure confirmation results are as follows:1H NMR(500MHz,CDCl3,ppm)δ7.63-7.55(m,1H),7.31-7.12(m,2H),6.97-6.86(m,2H)；13C NMR(125MHz,CDCl3,ppm)δ166.2(dd,J＝253.9,10.0Hz),147.1(dm,J＝247.0Hz),146.0(dm,J＝248.3Hz),137.9(t,J＝11.8Hz),121.9-119.8(m),117.8-115.9(m),112.2-111.6(m),110.3(t,J＝22.5Hz)；19F NMR(377MHz,CDCl3,ppm)δ-96.7,-130.2～-130.5(m),-138.6～-138.9(m)；11B NMR(128MHz,CDCl3,ppm)δ61.6；HRMS(APCI)calcd.for C18H4BF10(M-H):421.0252,Found:421.0254.
the compound synthesized by the structural identification is determined to be the target compound 2, 6-difluorophenylbis (2,3,5, 6-tetrafluorophenyl) borane shown in the formula II.
Example 2 preparation of Compound of formula V-a
The reaction equation is as follows:
the specific operation is as follows: in a glove box, at room temperature, oxazoline (0.0062g, 0.025mmol) shown in formula I, borane (0.0106g, 0.025mmol) shown in formula II, 6-bromo-3-isopropyl chromone (0.1336g,0.5mmol) shown in formula VI-a and 2.5mL mesitylene are added into a reaction tube, stirred at room temperature to dissolve the mesitylene, then the mixture is moved into a high-pressure reaction kettle to be filled with hydrogen (40bar), stirred at 30 ℃ for 24 hours, and then the mixture is concentrated by rotary evaporation and purified by silica gel column chromatography, wherein the yield is 95% and the ee value is 95%.
The structure confirmation results are as follows: [ alpha ] to]D 25＝+45.2(c 0.91,CHCl3)(95％ee)；IR(film):2962,1695,1475,1274,821cm-1；1H NMR(500MHz,CDCl3,ppm)δ7.99(d,J＝2.5Hz,1H),7.52(dd,J＝9.0,2.5Hz,1H),6.85(d,J＝9.0Hz,1H),4.54-4.44(m,2H),2.42-2.33(m,1H),2.33-2.19(m,1H),1.04(d,J＝7.0Hz,3H),1.00(d,J＝6.5Hz,3H)；13C NMR(125MHz,CDCl3,ppm)δ193.2,160.5,138.4,130.0,122.5,119.9,114.1,68.8,52.1,25.8,20.7,19.8；HRMS(APCI)calcd.for C12H14O2Br(M+H):269.0172,Found:269.0169.
The compound synthesized by the structural identification is determined to be the target compound (S) -6-bromo-3-isopropyl chromanone shown in the formula V-a.
Example 3 preparation of Compound of formula V-b
The reaction equation is as follows:
the specific operation is as follows: in a glove box, at room temperature, oxazoline (0.0062g, 0.025mmol) shown in formula I, borane (0.0106g, 0.025mmol) shown in formula II, 6-chloro-3-isopropyl chromone (0.1114g,0.5mmol) shown in formula VI-b and 2.5mL mesitylene are added into a reaction tube, stirred at room temperature to dissolve the mesitylene, then the mixture is moved into a high-pressure reaction kettle to be filled with hydrogen (40bar), stirred at 30 ℃ for 24 hours, concentrated by rotary evaporation and purified by silica gel column chromatography, the yield is 96%, and the ee value is 95%.
The structure confirmation results are as follows: [ alpha ] to]D 25＝+45.2(c 0.98,CHCl3)(95％ee)；IR(film):2963,1694,1478,1275,824cm-1；1H NMR(500MHz,CDCl3,ppm)δ7.84(d,J＝3.0Hz,1H),7.39(dd,J＝8.5,2.5Hz,1H),6.91(d,J＝9.0Hz,1H),4.54-4.45(m,2H),2.40-2.33(m,1H),2.33-2.23(m,1H),1.04(d,J＝6.5Hz,3H),1.01(d,J＝7.0Hz,3H)；13C NMR(125MHz,CDCl3,ppm)δ193.4,160.1,135.7,127.0,126.9,122.0,119.5,68.9,52.1,25.8,20.7,19.8；HRMS(APCI)calcd.for C12H12O2Cl(M-H):223.0531,Found:223.0523.
The compound synthesized by the structural identification is determined to be the target compound (S) -6-chloro-3-isopropyl chromanone shown in the formula V-b.
Example 4 preparation of Compounds of formula V-c
The reaction equation is as follows:
the specific operation is as follows: in a glove box, at room temperature, oxazoline (0.0062g, 0.025mmol) shown in formula I, borane (0.0106g, 0.025mmol) shown in formula II, 3-isopropyl-6-phenylchromone (0.1322g,0.5mmol) shown in formula VI-c and 2.5mL mesitylene are added into a reaction tube, stirred at room temperature to dissolve the mesitylene, then the mixture is moved into a high-pressure reaction kettle to be filled with hydrogen (40bar), stirred at 30 ℃ for 48 hours, concentrated by rotary evaporation and purified by silica gel column chromatography, the yield is 95%, and the ee value is 92%.
The structure confirmation results are as follows: [ alpha ] to]D 25＝+52.1(c 0.70,CHCl3)(92％ee)；IR(film):2960,1691,1480,1297,762cm-1；1H NMR(500MHz,CDCl3,ppm)δ8.13(d,J＝2.5Hz,1H),7.71(dd,J＝8.5,2.5Hz,1H),7.62-7.53(m,2H),7.46-7.38(m,2H),7.38-7.29(m,1H),7.02(d,J＝9.0Hz,1H),4.60-4.48(m,2H),2.45-2.29(m,2H),1.06(d,J＝6.5Hz,3H),1.03(d,J＝7.0Hz,3H)；13C NMR(125MHz,CDCl3,ppm)δ194.5,161.0,139.9,134.6,134.5,129.0,127.5,126.9,125.7,121.3,118.3,68.8,52.5,25.8,20.8,19.9；HRMS(ESI)calcd.for C18H19O2(M+H):267.1380,Found:267.1375.
The compound synthesized by the structural identification is determined to be the target compound (S) -3-isopropyl-6-benzene chromanone shown in the formula V-c.
Example 5 preparation of Compounds of formula V-d
The reaction equation is as follows:
the specific operation is as follows: in a glove box, at room temperature, oxazoline (0.0062g, 0.025mmol) shown in formula I, borane (0.0106g, 0.025mmol) shown in formula II, 3-isopropyl-6- (4-methoxyphenyl) chromone (0.1472g,0.5mmol) shown in formula VI-d and 2.5mL mesitylene are added into a reaction tube, stirred at room temperature to dissolve the mesitylene, then the mixture is transferred into a high-pressure reaction kettle to be filled with hydrogen (40bar), stirred at 30 ℃ for 48 hours, concentrated by rotary evaporation and purified by silica gel column chromatography, the yield is 95%, and the ee value is 92%.
The structure confirmation results are as follows: [ alpha ] to]D 25＝+57.5(c 0.67,CHCl3)(92％ee)；IR(film):2961,1689,1486,1261,823cm-1；1H NMR(500MHz,CDCl3,ppm)δ8.07(d,J＝2.5Hz,1H),7.66(dd,J＝8.5,2.5Hz,1H),7.56-7.44(m,2H),7.00(d,J＝8.5Hz,1H),6.98-6.93(m,2H),4.58-4.43(m,2H),3.84(s,3H),2.43-2.29(m,2H),1.06(d,J＝6.5Hz,3H),1.03(d,J＝7.0Hz,3H)；13C NMR(125MHz,CDCl3,ppm)δ194.6,160.6,159.3,134.3,134.2,132.5,128.0,125.0,121.2,118.2,114.5,68.8,55.5,52.5,25.8,20.8,19.9；HRMS(APCI)calcd.for C19H21O3(M+H):297.1485,Found:297.1480.
The compound synthesized by the structural identification is confirmed to be the target compound (S) -3-isopropyl-6- (4-methoxyphenyl) chromanone shown in the formula V-d.
Example 6 preparation of Compounds of formula V-e
The reaction equation is as follows:
the specific operation is as follows: in a glove box, at room temperature, oxazoline (0.0062g, 0.025mmol) shown in formula I, borane (0.0106g, 0.025mmol) shown in formula II, 3-isopropyl-6- (4-methylphenyl) chromone (0.1392g,0.5mmol) shown in formula VI-e and 2.5mL mesitylene are added into a reaction tube, stirred at room temperature to dissolve the mesitylene, then the mixture is transferred into a high-pressure reaction kettle to be filled with hydrogen (40bar), stirred at 30 ℃ for 48 hours, concentrated by rotary evaporation and purified by silica gel column chromatography, the yield is 97%, and the ee value is 93%.
The structure confirmation results are as follows: [ alpha ] to]D 25＝+58.9(c 0.67,CHCl3)(93％ee)；IR(film):2961,1690,1485,1262,812cm-1；1H NMR(500MHz,CDCl3,ppm)δ8.10(d,J＝2.5Hz,1H),7.69(dd,J＝8.5,2.5Hz,1H),7.47(d,J＝8.0Hz,2H),7.24(d,J＝8.0Hz,2H),7.01(d,J＝8.5Hz,1H),4.57-4.48(m,2H),2.43-2.29(m,5H),1.06(d,J＝6.5Hz,3H),1.03(d,J＝6.5Hz,3H)；13C NMR(125MHz,CDCl3,ppm)δ194.6,160.8,137.2,137.0,134.6,134.4,129.8,126.8,125.4,121.3,118.2,68.8,52.5,25.8,21.3,20.8,19.9；HRMS(ESI)calcd.for C19H21O2(M+H):281.1536,Found:281.1534.
The compound synthesized by the structural identification is confirmed to be the target compound (S) -3-isopropyl-6- (4-methylphenyl) chromanone shown as the formula V-e.
Example 7 preparation of Compounds of formula V-f
The reaction equation is as follows:
the specific operation is as follows: in a glove box, at room temperature, oxazoline (0.0062g, 0.025mmol) shown in formula I, borane (0.0106g, 0.025mmol) shown in formula II, 3-isopropyl-6- (4-trifluoromethylphenyl) chromone (0.1662g,0.5mmol) shown in formula VI-f and 2.5mL mesitylene are added into a reaction tube, stirred at room temperature to dissolve the mesitylene, then the mixture is transferred into a high-pressure reaction kettle to be filled with hydrogen (40bar), stirred at 30 ℃ for 48 hours, concentrated by rotary evaporation, purified by silica gel column chromatography, the yield is 98%, and the ee value is 93%.
The structure confirmation results are as follows: [ alpha ] to]D 26＝+42.9(c 0.79,CHCl3)(93％ee)；IR(film):2936,1693,1326,1123,825cm-1；1H NMR(500MHz,CDCl3,ppm)δ8.14(d,J＝2.5Hz,1H),7.74-7.64(m,5H),7.06(d,J＝8.5Hz,1H),4.59-4.51(m,2H),2.46-2.39(m,1H),2.39-2.29(m,1H),1.07(d,J＝6.5Hz,3H),1.04(d,J＝7.0Hz,3H)；13C NMR(125MHz,acetone-d6,ppm)δ194.0,162.5,144.4,135.0,133.2,129.5(q,J＝32.3Hz),128.0,126.7(q,J＝3.8Hz),126.1,125.5(q,J＝269.3Hz),122.2,119.4,69.5,52.6,26.4,20.7,19.8；19F NMR(377MHz,CDCl3,ppm)δ-62.4；HRMS(APCI)calcd.for C19H18O2F3(M+H):335.1253,Found:335.1248.
The compound synthesized by the structural identification is confirmed to be the target compound (S) -3-isopropyl-6- (4-trifluoromethylphenyl) chromanone shown in the formula V-f.
Example 8 preparation of Compound of formula V-g
The reaction equation is as follows:
the specific operation is as follows: in a glove box, at room temperature, oxazoline (0.0062g, 0.025mmol) shown in formula I, borane (0.0106g, 0.025mmol) shown in formula II, 3-isopropyl-6- (3-methylphenyl) chromone (0.1392g,0.5mmol) shown in formula VI-g and 2.5mL mesitylene are added into a reaction tube, stirred at room temperature to dissolve the mesitylene, then the mixture is transferred into a high-pressure reaction kettle to be filled with hydrogen (40bar), stirred at 30 ℃ for 72 hours, concentrated by rotary evaporation and purified by silica gel column chromatography, the yield is 95%, and the ee value is 92%.
The structure confirmation results are as follows: [ alpha ] to]D 26＝+51.9(c 0.80,CHCl3)(92％ee)；IR(film):2960,1690,1612,1480,1269,786cm-1；1H NMR(500MHz,CDCl3,ppm)δ8.11(d,J＝2.5Hz,1H),7.70(dd,J＝8.5,2.5Hz,1H),7.44-7.35(m,2H),7.31(t,J＝8.0Hz,1H),7.15(d,J＝7.5Hz,1H),7.01(d,J＝8.5Hz,1H),4.58-4.46(m,2H),2.46-2.26(m,5H),1.06(d,J＝6.5Hz,3H),1.03(d,J＝7.0Hz,3H)；13C NMR(125MHz,CDCl3,ppm)δ194.6,161.0,139.8,138.7,134.8,134.5,128.9,128.2,127.7,125.6,124.0,121.2,118.2,68.8,52.5,25.8,21.7,20.8,19.9；HRMS(APCI)calcd.for C19H21O2(M+H):281.1536,Found:281.1534.
The compound synthesized by the structural identification is confirmed to be the target compound (S) -3-isopropyl-6- (3-methylphenyl) chromanone shown in the formula V-g.
Example 9 preparation of Compounds of formula V-h
The reaction equation is as follows:
the specific operation is as follows: in a glove box, at room temperature, oxazoline (0.0062g, 0.025mmol) shown in formula I, borane (0.0106g, 0.025mmol) shown in formula II, 3-isopropyl-6- (3-methylphenyl) chromone (0.1392g,0.5mmol) shown in formula VI-h and 2.5mL mesitylene are added into a reaction tube, stirred at room temperature to dissolve the mesitylene, then the mixture is transferred into a high-pressure reaction kettle to be filled with hydrogen (40bar), stirred at 30 ℃ for 72 hours, concentrated by rotary evaporation and purified by silica gel column chromatography, the yield is 98%, and the ee value is 90%.
The structure confirmation results are as follows: [ alpha ] to]D 24＝+41.0(c 0.51,CHCl3)(90％ee)；IR(film):2961,1691,1614,1480,1256,762cm-1；1H NMR(500MHz,CDCl3,ppm)δ7.85(d,J＝2.5Hz,1H),7.43(dd,J＝8.5,2.5Hz,1H),7.28-7.17(m,4H),6.99(d,J＝8.0Hz,1H),4.58-4.47(m,2H),2.46-2.31(m,2H),2.27(s,3H),1.06(d,J＝7.0Hz,3H),1.04(d,J＝7.0Hz,3H)；13C NMR(125MHz,CDCl3,ppm)δ194.5,160.6,140.6,136.8,135.5,135.3,130.6,130.0,127.8,127.6,126.1,120.8,117.5,68.8,52.4,25.7,20.8,20.7,19.8；HRMS(APCI)calcd.for C19H21O2(M+H):281.1536,Found:281.1533.
The compound synthesized by the structural identification is confirmed to be the target compound (S) -3-isopropyl-6- (2-methylphenyl) chromanone shown in the formula V-h.
Example 10 preparation of Compound of formula V-i
The reaction equation is as follows:
the specific operation is as follows: in a glove box, at room temperature, oxazoline (0.0062g, 0.025mmol) shown in formula I, borane (0.0106g, 0.025mmol) shown in formula II, 7-bromo-3-isopropyl chromone (0.1336g,0.5mmol) shown in formula VI-I and 2.5mL mesitylene are added into a reaction tube, stirred at room temperature to dissolve the mesitylene, then the mixture is moved into a high-pressure reaction kettle to be filled with hydrogen (40bar), stirred at 30 ℃ for 72 hours, concentrated by rotary evaporation, purified by silica gel column chromatography, the yield is 93%, and the ee value is 92%.
The structure confirmation results are as follows: [ alpha ] to]D 25＝+13.3(c 0.95,CHCl3)(92％ee)；IR(film):2961,1693,1595,1420,859cm-1；1H NMR(500MHz,CDCl3,ppm)δ7.74(d,J＝8.5Hz,1H),7.22-7.03(m,2H),4.56-4.43(m,2H),2.40-2.34(m,1H),2.34-2.23(m,1H),1.03(d,J＝7.0Hz,3H),1.00(d,J＝7.0Hz,3H)；13C NMR(125MHz,CDCl3,ppm)δ193.6,161.8,130.2,128.8,125.1,121.0,120.2,69.1,52.2,25.8,20.7,19.8；HRMS(APCI)calcd.for C12H14O2Br(M+H):269.0172,Found:269.0167.
The compound synthesized by the structural identification is determined to be the target compound (S) -7-bromo-3-isopropyl chromanone shown in the formula V-i.
Example 11 preparation of Compound of formula V-j
The reaction equation is as follows:
the specific operation is as follows: in a glove box, at room temperature, oxazoline (0.0062g, 0.025mmol) shown in formula I, borane (0.0106g, 0.025mmol) shown in formula II, 7-methyl-3-isopropyl chromone (0.1012g,0.5mmol) shown in formula VI-j and 2.5mL mesitylene are added into a reaction tube, stirred at room temperature to dissolve the mesitylene, then the mixture is moved into a high-pressure reaction kettle to be filled with hydrogen (40bar), stirred at 30 ℃ for 72 hours, concentrated by rotary evaporation, purified by silica gel column chromatography, the yield is 91%, and the ee value is 72%.
The structure confirmation results are as follows: [ alpha ] to]D 25＝+25.0(c 0.76,CHCl3)(72％ee)；IR(film):2962,1687,1616,1154,818cm-1；1H NMR(500MHz,CDCl3,ppm)δ7.78(d,J＝8.0Hz,1H),6.82(dd,J＝7.5,1.0Hz,1H),6.74(s,1H),4.55-4.38(m,2H),2.39-2.23(m,5H),1.03(d,J＝6.5Hz,3H),1.00(d,J＝6.5Hz,3H)；13C NMR(125MHz,CDCl3,ppm)δ194.3,161.6,147.3,127.5,122.9,119.0,117.8,68.7,52.3,25.9,22.1,20.8,19.9；HRMS(APCI)calcd.for C13H17O2(M+H):205.1223,Found:205.1223.
The compound synthesized by the structural identification is determined to be the target compound (S) -7-methyl-3-isopropyl chromanone shown in the formula V-j.
Example 12 preparation of a Compound of formula V-k
The reaction equation is as follows:
the specific operation is as follows: in a glove box, at room temperature, oxazoline (0.0062g, 0.025mmol) shown in formula I, borane (0.0106g, 0.025mmol) shown in formula II, 8-bromo-3-isopropyl chromone (0.1336g,0.5mmol) shown in formula VI-k and 2.5mL mesitylene are added into a reaction tube, stirred at room temperature to dissolve the mesitylene, then the mixture is moved into a high-pressure reaction kettle to be filled with hydrogen (40bar), stirred at 30 ℃ for 72 hours, concentrated by rotary evaporation, purified by silica gel column chromatography, the yield is 95%, and the ee value is 89%.
The structure confirmation results are as follows: [ alpha ] to]D 24＝+4.3(c 0.74,CHCl3)(89％ee)；IR(film):2961,1696,1439,1285,748cm-1；1H NMR(500MHz,CDCl3,ppm)δ7.86(dd,J＝8.0,1.5Hz,1H),7.71(dd,J＝8.0,1.5Hz,1H),6.91(t,J＝8.0Hz,1H),4.67-4.54(m,2H),2.47-2.39(m,1H),2.39-2.26(m,1H),1.05(d,J＝7.0Hz,3H),1.02(d,J＝7.0Hz,3H)；13C NMR(125MHz,CDCl3,ppm)δ193.6,158.0,139.1,127.0,122.5,122.2,111.5,69.4,51.9,25.6,20.7,19.8；HRMS(APCI)calcd.for C12H14O2Br(M+H):269.0172,Found:269.0169.
The compound synthesized by structure identification is determined to be a target compound (S) -8-bromo-3-isopropyl chromanone shown in formula V-k.
Example 13 preparation of Compound of formula V-l
The reaction equation is as follows:
the specific operation is as follows: in a glove box, at room temperature, oxazoline (0.0062g, 0.025mmol) shown in formula I, borane (0.0106g, 0.025mmol) shown in formula II, 3-isopropyl chromone (0.0942g,0.5mmol) shown in formula VI-l and 2.5mL mesitylene are added into a reaction tube, stirred at room temperature to be dissolved, then moved into a high-pressure reaction kettle to be filled with hydrogen (40bar), stirred at 40 ℃ for 72 hours, concentrated by rotary evaporation, purified by silica gel column chromatography, the yield is 92%, and the ee value is 87%.
The structure confirmation results are as follows: [ alpha ] to]D 26＝+32.6(c 0.94,CHCl3)(87％ee)；IR(film):2962,1691,1462,1307,759cm-1；1H NMR(500MHz,CDCl3,ppm)δ7.89(dd,J＝7.5,1.5Hz,1H),7.51-7.38(m,1H),7.04-6.97(m,1H),6.94(d,J＝8.5Hz,1H),4.55-4.44(m,2H),2.42-2.24(m,2H),1.04(d,J＝6.5Hz,3H),1.01(d,J＝7.0Hz,3H)；13C NMR(125MHz,CDCl3,ppm)δ194.6,161.6,135.8,127.6,121.5,121.3,117.8,68.7,52.4,25.8,20.8,19.8；HRMS(APCI)calcd.for C12H15O2(M+H):191.1067,Found:191.1066.
The compound synthesized by the structural identification is determined to be the target compound (S) -3-isopropyl chromanone shown in the formula V-l.
Example 14 preparation of Compound of formula V-m
The reaction equation is as follows:
the specific operation is as follows: in a glove box, at room temperature, oxazoline (0.0062g, 0.025mmol) shown in formula I, borane (0.0106g, 0.025mmol) shown in formula II, 3-ethyl chromone (0.0871g,0.5mmol) shown in formula VI-m and 2.5mL mesitylene are added into a reaction tube, stirred at room temperature to be dissolved, then moved into a high-pressure reaction kettle to be filled with hydrogen (40bar), stirred at 40 ℃ for 72 hours, concentrated by rotary evaporation, purified by silica gel column chromatography, the yield is 93 percent, and the ee value is 51 percent.
The structure confirmation results are as follows: [ alpha ] to]D 25＝-13.2(c 0.63,CHCl3)(51％ee)；IR(film):2969,1690,1605,1478,1302,758cm-1；1H NMR(500MHz,CDCl3,ppm)δ7.90(dd,J＝8.0,1.5Hz,1H),7.51-7.42(m,1H),7.06-6.98(m,1H),6.95(dd,J＝8.5,0.5Hz,1H),4.53(dd,J＝11.5,4.5Hz,1H),4.30(dd,J＝11.5,8.5Hz,1H),2.67-2.52(m,1H),2.00-1.83(m,1H),1.63-1.53(m,1H),1.04(t,J＝7.5Hz,3H)；13C NMR(125MHz,CDCl3,ppm)δ194.7,161.7,135.9,127.6,121.5,120.9,117.9,70.4,47.6,19.9,11.7；HRMS(APCI)calcd.for C11H13O2(M+H):177.0910,Found:177.0910.
The compound synthesized by structure identification is determined to be the target compound (S) -3-acetochlor shown as a formula V-m.
Example 15 preparation of a Compound of formula V-n
The reaction equation is as follows:
the specific operation is as follows: in a glove box, at room temperature, oxazoline (0.0062g, 0.025mmol) shown in formula I, borane (0.0106g, 0.025mmol) shown in formula II, 3-methyl chromone (0.0801g,0.5mmol) shown in formula VI-n and 2.5mL mesitylene are added into a reaction tube, stirred at room temperature to be dissolved, then moved into a high-pressure reaction kettle to be filled with hydrogen (40bar), stirred at 40 ℃ for 72 hours, and subjected to rotary evaporation concentration and silica gel column chromatography purification, wherein the yield is 93 percent, and the ee value is 33 percent.
The structure confirmation results are as follows: [ alpha ] to]D 26＝-18.6(c 0.94,CHCl3)(33％ee)；1H NMR(500MHz,CDCl3,ppm)δ7.90(dd,J＝7.5,2.0Hz,1H),7.52-7.41(m,1H),7.06-6.99(m,1H),6.96(d,J＝8.0Hz,1H),4.50(dd,J＝11.0,5.0Hz,1H),4.16(t,J＝11.0Hz,1H),2.93-2.80(m,1H),1.22(d,J＝7.0Hz,3H)；13C NMR(125MHz,CDCl3,ppm)δ195.0,161.9,135.9,127.6,121.6,120.8,117.9,72.4,40.9,10.9.
The compound synthesized by the structural identification is determined to be the target compound (S) -3-methyl chromanone shown in the formula V-n.
Example 16 preparation of the Compound of formula V-o
The reaction equation is as follows:
the specific operation is as follows: in a glove box, at room temperature, oxazoline (0.0062g, 0.025mmol) shown in formula I, borane (0.0106g, 0.025mmol) shown in formula II, 3-phenylchromone (0.1112g,0.5mmol) shown in formula VI-o and 2.5mL mesitylene are added into a reaction tube, stirred at room temperature to be dissolved, then moved into a high-pressure reaction kettle to be filled with hydrogen (40bar), stirred at 30 ℃ for 72 hours, concentrated by rotary evaporation, purified by silica gel column chromatography, the yield is 96%, and the ee value is 44%.
The structure confirmation results are as follows: [ alpha ] to]D 26＝-2.1(c 0.67,CHCl3)(44％ee)；1H NMR(500MHz,CDCl3,ppm)δ7.96(dd,J＝8.0,1.5Hz,1H),7.57-7.45(m,1H),7.41-7.25(m,5H),7.10-6.97(m,2H),4.73-4.63(m,2H),4.00(dd,J＝8.5,6.5Hz,1H)；13C NMR(125MHz,CDCl3,ppm)δ192.4,161.8,136.3,135.2,129.1,128.8,128.0,127.9,121.8,121.3,118.1,71.7,52.5.
The compound synthesized by the structural identification is determined to be the target compound (S) -3-benzene chromanone shown in the formula V-o.
Example 17 preparation of Compound of formula V-p
The reaction equation is as follows:
the specific operation is as follows: in a glove box, at room temperature, oxazoline (0.0062g, 0.025mmol) shown in formula I, borane (0.0106g, 0.025mmol) shown in formula II, 3- (2-methylphenyl) chromone (0.1182g,0.5mmol) shown in formula VI-p and 2.5mL mesitylene are added into a reaction tube, stirred at room temperature to be dissolved, then the mixture is moved into a high-pressure reaction kettle to be filled with hydrogen (40bar), stirred at 30 ℃ for 72 hours, concentrated by rotary evaporation, purified by silica gel column chromatography, the yield is 98 percent, and the ee value is 80 percent.
The structure confirmation results are as follows: [ alpha ] to]D 25＝+11.4(c 0.81,CHCl3)(80％ee)；IR(film):2920,1690,1605,1477,1287,764cm-1；1H NMR(500MHz,CDCl3,ppm)δ7.99(dd,J＝7.5,1.5Hz,1H),7.59-7.46(m,1H),7.29-7.15(m,3H),7.11-6.99(m,3H),4.66-4.53(m,2H),4.35-4.25(m,1H),2.38(s,3H)；13C NMR(125MHz,acetone-d6,ppm)δ192.5,162.7,138.1,136.7,135.3,131.3,129.1,128.2,128.0,126.9,122.4,122.2,118.7,71.8,49.7,20.0；HRMS(APCI)calcd.for C16H15O2(M+H):239.1067,Found:239.1065.
The compound synthesized by the structural identification is confirmed to be the target compound (S) -3- (2-methylphenyl) chromanone shown in the formula V-p.
Claims (7)
1. Use of a borane of the formula II: the borane shown in the formula II and the chiral oxazoline compound are matched to catalyze and hydrogenate chromanone compounds to prepare 3-bit substituted chromanone compounds;
the structural formula of the chiral oxazoline compound is shown in a formula I;
the structural formula of the chromanone compound is shown as formula VI:
the structural formula of the 3-substituted chromanone compound is shown as the formula V:
in the formulae VI and V, R1Represents a substituent on a benzene ring, and is H, alkyl with 1-6 carbon atoms, aryl with 6-7 carbon atoms or halogen; r is2Is an alkyl group having 1 to 6 carbon atoms or an aryl group having 6 to 7 carbon atoms.
2. The preparation method of the 3-substituted chiral chromanone compound shown as the formula V comprises the following steps:
reacting a compound shown as a formula VI with hydrogen in a catalytic system of oxazoline shown as a formula I and borane shown as a formula II to obtain the compound;
in the formulae VI and V, R1Represents a substituent on a benzene ring, and is H, alkyl with 1-6 carbon atoms, aryl with 6-7 carbon atoms or halogen; r2Is an alkyl group having 1 to 6 carbon atoms or an aryl group having 6 to 7 carbon atoms.
3. The method of claim 2, wherein: the molar ratio of the oxazoline shown in the formula I, the borane shown in the formula II and the compound shown in the formula VI is 1: 1: 20 to 20.
4. The production method according to claim 2 or 3, characterized in that: the reaction is carried out in a high-pressure kettle, and the pressure of the hydrogen is 40-60 bar.
5. The method of manufacturing according to claim 4, characterized in that: the reaction is carried out in an organic solvent; the organic solvent is mesitylene.
6. The method of claim 5, wherein: the reaction temperature is 30-40 ℃, and the reaction time is 24-72 hours.
7. The method of claim 6, wherein: after the reaction is finished, the method also comprises the step of separating and purifying the 3-substituted chiral chromanone compound shown in the formula V by column chromatography;
the column chromatography conditions were as follows:
the column filler is 200-300 meshes of silica gel; the eluent is: the volume ratio is 4: 1 of petroleum ether and dichloromethane.
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| The diastereoselective synthesis of octahedral cationic iridium hydride complexes with a stereogenic metal centre;Nicolas Humbert et al.;《Chem. Commun.》;20160802;第52卷;第10629-10631页 * |
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