CN113214119A - Selective addition method of dienamine and phenylboronic acid controlled by small steric hindrance - Google Patents

Selective addition method of dienamine and phenylboronic acid controlled by small steric hindrance Download PDF

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CN113214119A
CN113214119A CN202110300752.XA CN202110300752A CN113214119A CN 113214119 A CN113214119 A CN 113214119A CN 202110300752 A CN202110300752 A CN 202110300752A CN 113214119 A CN113214119 A CN 113214119A
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mmol
phenylboronic acid
dienamine
selective addition
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CN113214119B (en
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刘会
杜鑫
董旭
刘青
李梓睿
杨怡
耿文哲
杨艺
刘云霞
黎新
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Shandong University of Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
    • C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/42—Separation; Purification; Stabilisation; Use of additives
    • C07C303/44—Separation; Purification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C311/21—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/61—Halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C07D307/81—Radicals substituted by nitrogen atoms not forming part of a nitro radical

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Abstract

The invention discloses a method for preparing selective addition of dienamine and phenylboronic acid controlled by small steric hindrance, and belongs to the technical field of organic compound process application. The method has the advantages of mild reaction conditions, easy preparation of raw materials, simple reaction operation, higher yield and excellent regioselectivity.

Description

Selective addition method of dienamine and phenylboronic acid controlled by small steric hindrance
Technical Field
The invention particularly relates to a selective addition method for preparing small-steric-hindrance-controlled dienamine and phenylboronic acid, and belongs to the technical field of organic compound process application.
Background
The reaction involving the dienamine compound not only has regioselectivity and stereoselectivity, but also, more importantly, the resulting products all have the function of nitrogen. Nitrogen-containing structures are ubiquitous in natural and non-natural products of medical interest. Has important significance for developing new treatment methods. The dienamines are very susceptible to hydrolysis, polymerization and isomerization even at low temperatures and therefore present no minor challenges in preparation and handling. Therefore, it is an urgent need to develop a bisaniline compound having an appropriate balance between stability and reactivity. The bianiline compounds are receiving more and more attention due to their unique reactivity, selectivity, effectiveness and stability, and the research reports on their functionalization are increasing. The method provides a brand new method for preparing the selective addition of the allenamine and the phenylboronic acid controlled by small steric hindrance.
Disclosure of Invention
The invention provides a method for preparing the selective addition of the dienamine and the phenylboronic acid controlled by small steric hindrance for the first time, and the conversion of the dienamine can be efficiently realized by adopting a metal palladium catalyst.
As shown in FIG. 1, the present invention utilizes 4-methyl-N- (propyl-1, 2-dien-1-yl) -N- (p-tolyl) benzenesulfonamide compound (1) and phenylboronic acid (2) as reaction raw materials, and reacts in a reaction solvent system under the action of a metal palladium catalyst to synthesize benzenesulfonamide derivative (3).
In the present invention, R1Is an aryl group; r is alkyl, ester group, halogen, heterocycle and aryl.
In the present invention, R1R includes, but is not limited to, the above groups, for example, R1R may also be a polysubstituent.
In the present invention, the palladium catalyst is PdCl2(dppe)、PdCl2(PPh3)2、Pd(MeCN)2Cl2。
Preferably, the palladium catalyst is Pd (MeCN)2Cl2。
The amount of the catalyst is 10 mol% of the raw material 1.
Preferably, the catalyst is used in an amount of 10 mol%.
In the invention, the reaction solvent system is toluene, tetrahydrofuran and 1, 4-dioxane.
Preferably, the reaction is carried out in 1, 4-dioxane.
In the present invention, the reaction base is cesium carbonate (Cs)2CO3) Cesium fluoride (CsF), potassium phosphate (K)3PO4)。
Preferably, the base is potassium phosphate.
The amount of the base is 2.0 equivalents of the amount of the raw material 1.
In the present invention, the synthesis reaction is at 50oAnd C, performing the reaction.
Preferably, it is at 50oAnd C, carrying out the reaction.
In the present invention, the synthesis reaction time is 0.5 to 5 hours.
Preferably, the reaction is carried out for 1 hour.
Specifically, in the synthesis reaction of the invention, palladium dichloride acetonitrile (X mol%) and potassium phosphate (Z mol%) are added into a reaction tube A in a nitrogen environment, then N- (2-iodoethyl) -4-methyl-N- (2-methyl-1-phenylallyl) benzene sulfonamide compound (1, W mmol) and phenylboronic acid (2, N mmol) are added into the reaction tube, and finally, a solvent (V mL) is added. 50oC, reacting for 1 hour. The progress of the reaction was checked by TLC. After the reaction is finished, adding silica gel for spin drying, performing column chromatography, and separating to obtain a target product 3.
The advantages of the synthesis reaction of the present invention include: the raw materials used in the synthesis method are mature and efficient in synthesis route, and have very stable performance without special storage conditions. The used basic medicines are cheap and easily available, and various metal catalysts and ligands used are commercial catalysts, can be purchased commercially, are very stable, have the characteristics of low cost, high yield, simple process and less pollution, and are completely suitable for large-scale production.
The invention discloses a selective addition method for preparing dienamine and phenylboronic acid controlled by small steric hindrance, which is a novel method, innovatively realizes 1,2-anti-Markovnikov hydroarylation of dienamine and constructs a new Csp 2-Csp 3A key. The invention discloses a method for preparing (E) -N- (3- (2-phenyl) prop-1-ene-1-yl) -4-methyl-N- (p-tolyl) benzene sulfonamide derivatives by taking 4-methyl-N- (propyl 1, 2-diene-1-yl) -N- (p-tolyl) benzene sulfonamide compounds and phenylboronic acid as raw materials under the action of a metal palladium catalyst. The operation method is simple, the reaction condition is mild, the reaction rate is high, and the yield is high.
Drawings
FIG. 1: the general reaction formula is shown;
FIG. 2: example 1;
FIG. 3: example 2;
FIG. 4: example 3;
FIG. 5: example 4;
FIG. 6: example 5;
FIG. 7: example 6;
FIG. 8: example 7;
FIG. 9: example 8;
FIG. 10: example 9;
FIG. 11: example 10;
FIG. 12: example 11;
FIG. 13: example 12;
FIG. 14: example 13;
FIG. 15: example 14;
FIG. 16: example 15;
FIG. 17: example 16;
FIG. 18: example 17;
FIG. 19: example 18;
FIG. 20: example 19;
FIG. 21: example 20;
Detailed Description
The present invention will be described in further detail with reference to the following specific examples, but the present invention is not limited to the following examples. Variations and advantages that may occur to those skilled in the art may be incorporated into the invention without departing from the spirit and scope of the inventive concept, and the scope of the appended claims is intended to be protected. The procedures, conditions, reagents, experimental methods and the like for carrying out the present invention are general knowledge and common general knowledge in the art except for the contents specifically mentioned below, and the present invention is not particularly limited. The data given in the examples below include specific operating and reaction conditions and products. The purity of the product was identified by nuclear magnetism.
Example 1
3a
FIG. 2
In a 25 mL reactor under nitrogen atmosphere, diacetonitrile palladium dichloride (5.0 mg, 0.02mmol) and potassium phosphate (85.0 mg, 0.40 mmol) were added, and substrates 1a (59.8 mg, 0.20 mmol) and 2a (38.0 mg, 0.24 mmol) were weighed into the reactor, and 1, 4-dioxane (2 mL) was added. Heating the reaction system to 50oC, reacting for 1 h. After the TLC detection reaction, the system was cooled to room temperature. Extraction with ethyl acetate, washing three times with 30mL of saturated sodium chloride solution, drying over anhydrous sodium sulfate, spin-drying on silica gel, and column chromatography gave 3a (82%) as a pale yellow liquid.1H NMR (400 MHz, CDCl3, δ ppm):7.47 (d, J = 7.6 Hz, 2H), 7.24-7.18 (m, 3H), 7.08-7.01 (m, 5H), 6.96 (d, J = 14 Hz, 1H), 6.75 (d, J = 7.6 Hz, 2H), 4.44-4.37 (m, 1H), 3.27 (d, J = 6.8 Hz, 2H), 2.36 (s, 3H), 2.26 (s, 3H).
13C NMR (100 MHz, CDCl3, δ ppm): 143.8, 139.0, 138.1, 135.9, 133.9, 133.8, 130.8, 130.1, 130.1, 129.8, 129.6, 129.4, 127.6, 127.5, 126.8, 108.9, 33.7, 21.7, 21.3.
HRMS (ESI) calculated value C23H22ClNO2S + Na 434.0957, actual value 434.0958.
Example 2
3a
FIG. 3
In a 25 mL test tube under nitrogen atmosphere1, 2-bis (diphenylphosphino) ethane palladium chloride (15.0 mg, 0.02mmol) and potassium phosphate (85.0 mg, 0.40 mmol) were charged into a reactor, substrates 1a (59.8 mg, 0.20 mmol) and 2a (38.0 mg, 0.24 mmol) were weighed into a reaction tube, and 1, 4-dioxane (2 mL) was added. Heating the reaction system to 50oC, reacting for 50 min. After the TLC detection reaction, the system was cooled to room temperature. Extraction with ethyl acetate, washing three times with 30mL of saturated sodium chloride solution, drying over anhydrous sodium sulfate, spin-drying on silica gel, and column chromatography gave 3a (68%) as a pale yellow liquid. The analytical data were as in example 1.
Example 3
3a：
FIG. 4
Under nitrogen atmosphere, bis (triphenylphosphine) palladium chloride (14.0 mg, 0.02mmol) and potassium phosphate (85.0 mg, 0.40 mmol) were added to a 25 mL tube reactor, and substrates 1a (59.8 mg, 0.20 mmol) and 2a (38.0 mg, 0.24 mmol) were weighed into the reaction tube, and 1, 4-dioxane (2 mL) was added. Heating the reaction system to 50oC, reacting for 50 min. After the TLC detection reaction, the system was cooled to room temperature. Extraction with ethyl acetate, washing three times with 30mL of saturated sodium chloride solution, drying over anhydrous sodium sulfate, spin-drying on silica gel, and column chromatography gave 3a (52%) as a pale yellow liquid. The analytical data were as in example 1.
Example 4
3a：
FIG. 5
In a 25 mL reactor under nitrogen atmosphere, diacetonitrile palladium dichloride (5.0 mg, 0.02mmol) and cesium carbonate (130.0 mg, 0.40 mmol) were added, and substrates 1a (59.8 mg, 0.20 mmol) and 2a (38.0 mg, 0.24 mmol) were weighed into the reactor, and 1, 4-dioxane (2 mL) was added. Heating the reaction system to 50oC, reacting for 1.5 h. After the TLC detection reaction, the system was cooled to room temperature. Extraction with ethyl acetate, washing three times with 30mL of saturated sodium chloride solution, drying over anhydrous sodium sulfate, spin-drying on silica gel, and column chromatography gave 3a (74%) as a pale yellow liquid. The analytical data were as in example 1.
Example 5
3a：
FIG. 6
Under nitrogen atmosphere inA25 mL reactor was charged with diacetonitrile palladium dichloride (5.0 mg, 0.02mmol) and cesium fluoride (61.0 mg, 0.40 mmol), and substrates 1a (59.8 mg, 0.20 mmol) and 2a (38.0 mg, 0.24 mmol) were weighed into the reactor, followed by addition of 1, 4-dioxane (2 mL). Heating the reaction system to 50oC, reacting for 0.5 h. After the TLC detection reaction, the system was cooled to room temperature. Extraction with ethyl acetate, washing three times with 30mL of saturated sodium chloride solution, drying over anhydrous sodium sulfate, spin-drying on silica gel, and column chromatography gave 3a (54%) as a pale yellow liquid. The analytical data were as in example 1.
Example 6
3a：
FIG. 7
In a 25 mL reactor under nitrogen atmosphere, diacetonitrile palladium dichloride (5.0 mg, 0.02mmol) and potassium phosphate (85.0 mg, 0.40 mmol) were added, and substrates 1a (59.8 mg, 0.20 mmol) and 2a (38.0 mg, 0.24 mmol) were weighed into the reactor, followed by addition of toluene (2 mL). Heating the reaction system to 50oAnd C, reacting for 30 min. After the TLC detection reaction, the system was cooled to room temperature. Extraction with ethyl acetate, washing three times with 30mL of saturated sodium chloride solution, drying over anhydrous sodium sulfate, spin-drying on silica gel, and column chromatography gave 3a (72%) as a pale yellow liquid. The analytical data were as in example 1.
Example 7
3a：
FIG. 8
In a 25 mL reactor under nitrogen atmosphere, diacetonitrile palladium dichloride (5.0 mg, 0.02mmol) and potassium phosphate (85.0 mg, 0.40 mmol) were added, and substrates 1a (59.8 mg, 0.20 mmol) and 2a (38.0 mg, 0.24 mmol) were weighed into the reactor, followed by addition of tetrahydrofuran (2 mL). Heating the reaction system to 50oC, reacting for 1.5 h. After the TLC detection reaction, the system was cooled to room temperature. Extraction with ethyl acetate, washing three times with 30mL of saturated sodium chloride solution, drying over anhydrous sodium sulfate, spin-drying on silica gel, and column chromatography gave 3a (36%) as a pale yellow liquid. The analytical data were as in example 1.
Example 8
3b：
FIG. 9
Under nitrogen atmosphere, a 25 mL reactor was charged withDiacetone palladium dichloride (5.0 mg, 0.02mmol), potassium phosphate (85.0 mg, 0.40 mmol), substrates 1b (66.0 mg, 0.20 mmol) and 2a (38.0 mg, 0.24 mmol) were weighed into a reaction tube, and 1, 4-dioxane (2 mL) was added. Heating the reaction system to 50oC, reacting for 1 h. After the TLC detection reaction, the system was cooled to room temperature. Extraction with ethyl acetate, washing three times with 30mL of saturated sodium chloride solution, drying over anhydrous sodium sulfate, spin-drying on silica gel, and column chromatography gave 3b as a pale yellow liquid (60%).1H NMR (400 MHz, CDCl3, δ ppm):7.54 (d, J = 7.6 Hz, 2H), 7.31 (d, J = 7.6 Hz, 1H), 7.27 (d, J = 7.2 Hz, 2H), 7.17-7.12 (m, 2H), 7.08 (d, J = 9.6 Hz, 1H), 7.05 (d, J = 14.4 Hz, 1H), 6.84 (dd, J = 16.8, 8.8 Hz, 4H), 4.52-4.45 (m, 1H), 3.79 (s, 3H), 3.39 (d, J= 6.8 Hz, 2H), 2.44 (s, 3H).
13C NMR (100 MHz, CDCl3, δ ppm): 159.7, 143.8, 138.2, 135.8, 133.9, 131.2, 130.9, 130.1, 129.6, 129.4, 128.9, 127.6, 127.5, 126.8, 114.6, 108.6, 55.4, 33.7, 21.6.
HRMS (ESI) calculated value C23H22ClNO3S + Na 450.0907, actual value 450.0910.
Example 9
3c：
FIG. 10 shows a schematic view of a
In a 25 mL reactor under nitrogen atmosphere, diacetonitrile palladium dichloride (5.0 mg, 0.02mmol) and potassium phosphate (85.0 mg, 0.40 mmol) were added, and the substrates 1c (66.0 mg, 0.20 mmol) and 2a (38.0 mg, 0.24 mmol) were weighed into the reactor, and 1, 4-dioxane (2 mL) was added. Heating the reaction system to 50oC, reacting for 5 hours. After the TLC detection reaction, the system was cooled to room temperature. Extraction with ethyl acetate, washing three times with 30mL of saturated sodium chloride solution, drying over anhydrous sodium sulfate, spin-drying on silica gel, and column chromatography gave 3c (51%) as a pale yellow liquid.1H NMR (400 MHz, CDCl3, δ ppm):8.19 (d, J = 8.8 Hz, 2H), 7.53 (d, J = 7.6 Hz, 2H), 7.33-7.29 (m, 3H), 7.21-7.14 (m, 4H), 7.09 (d, J = 8 Hz, 1H), 6.95 (d, J = 14 Hz, 1H), 4.66-4.59 (m, 1H), 3.42 (d, J = 6.8 Hz, 2H), 2.45 (s, 3H).
13C NMR (100 MHz, CDCl3, δ ppm): 147.3, 144.6, 143.2, 137.4, 135.0, 133.9, 130.7, 130.2, 129.9, 129.6, 127.9, 127.4, 127.0, 124.8, 112.0, 33.9, 21.7, 14.2.
HRMS (ESI) calculated value C22H19ClN2O4S + Na 465.0652, actual value 465.0654.
Example 10
3d：
FIG. 11
In a 25 mL reactor under nitrogen atmosphere, diacetonitrile palladium dichloride (5.0 mg, 0.02mmol) and potassium phosphate (85.0 mg, 0.40 mmol) were added, and substrates 1a (59.8 mg, 0.20 mmol) and 2b (36.0 mg, 0.24 mmol) were weighed into the reactor, and 1, 4-dioxane (2 mL) was added. Heating the reaction system to 50oC, reacting for 5 hours. After the TLC detection reaction, the system was cooled to room temperature. Extraction with ethyl acetate, washing three times with 30mL of saturated sodium chloride solution, drying over anhydrous sodium sulfate, spin-drying on silica gel, and column chromatography gave 3d (36%) as a pale yellow liquid.1H NMR (400 MHz, CDCl3, δ ppm):7.56 (d, J = 7.6 Hz, 2H), 7.28 (d, J = 8 Hz, 2H), 7.11 (d, J = 8 Hz, 2H), 7.01 (d, J = 13.2 Hz, 1H), 7.00 (d, J = 7.2 Hz, 2H), 6.83 (d, J = 8 Hz, 2H), 6.79 (d, J = 8 Hz, 2H), 4.54-4.47 (m, 1H), 3.77 (s, 3H), 3.22 (d, J = 7.2 Hz, 2H), 2.45 (s, 3H), 2.33 (s, 3H).
13C NMR (100 MHz, CDCl3, δ ppm): 157.9, 143.7, 139.0, 136.0, 134.0, 132.6, 130.1, 130.0,129.8, 129.7, 129.6, 129.2, 127.5, 113.7, 111.4, 55.3, 21.7, 21.2.
HRMS (ESI) calculated value C24H25NO3S + Na 430.1453, actual value 430.1457.
Example 11
3e：
FIG. 12
In a 25 mL reactor under nitrogen atmosphere, diacetone palladium dichloride (5.0 mg, 0.02mmol) and potassium phosphate were added(85.0 mg, 0.40 mmol), substrate 1a (59.8 mg, 0.20 mmol) and 2c (34.0 mg, 0.24 mmol) were weighed into a reaction tube, and 1, 4-dioxane (2 mL) was added. Heating the reaction system to 50oC, reacting for 1 h. After the TLC detection reaction, the system was cooled to room temperature. Extraction with ethyl acetate, washing three times with 30mL of saturated sodium chloride solution, drying over anhydrous sodium sulfate, spin-drying on silica gel, and column chromatography gave 3e (69%) as a pale yellow liquid.1H NMR (400 MHz, CDCl3, δ ppm):7.55 (d, J = 7.6 Hz, 2H), 7.28 (d, J = 8 Hz, 2H), 7.12 (d, J = 8 Hz, 2H), 7.05-7.01 (m, 3H), 6.93 (d, J = 8.8 Hz, 1H), 6.91 (d, J = 8 Hz, 1H), 6.83 (d, J = 7.6 Hz, 2H), 4.52-4.44 (m, 1H), 3.25 (d, J = 7.2 Hz, 2H), 2.45 (s, 3H), 2.33 (s, 3H).
13C NMR (100 MHz, CDCl3, δ ppm): 161.4 (d, J = 242.3 Hz), 143.8, 139.0, 136.2 (d, J = 3.1 Hz), 135.9, 133.8, 130.2, 130.1, 129.8, 129.6 (d, J= 8.1 Hz), 129.6, 127.5, 115.1(d, J = 21 Hz), 110.6, 35.2, 21.6, 21.2.
19F NMR (376 MHz, CDCl3, δ ppm): δ-117.3.
HRMS (ESI) calculated value C23H22FNO2S + Na 418.1253, actual value 418.1255.
Example 12
3f：
FIG. 13
In a 25 mL reactor under nitrogen atmosphere, diacetonitrile palladium dichloride (5.0 mg, 0.02mmol) and potassium phosphate (85.0 mg, 0.40 mmol) were added, and the substrates 1a (59.8 mg, 0.20 mmol) and 2d (85.0 mg, 0.24 mmol) were weighed into the reactor, and 1, 4-dioxane (2 mL) was added. Heating the reaction system to 50oC, reacting for 1.5 h. After the TLC detection reaction, the system was cooled to room temperature. Extraction with ethyl acetate, washing three times with 30mL of saturated sodium chloride solution, drying over anhydrous sodium sulfate, spin-drying on silica gel, and column chromatography gave 3f (36%) as a pale yellow liquid.1H NMR (400 MHz, CDCl3, δ ppm):7.55 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 4H), 7.21-7.18 (m, 2H), 7.13 (d, J = 8 Hz, 2H), 7.08 (d, J = 14 Hz, 1H), 6.84 (d, J = 7.6 Hz, 2H), 4.47-4.39 (m, 1H), 3.38 (d, J = 6.8 Hz, 2H), 2.44 (s, 3H), 2.33 (s, 3H).
13C NMR (100 MHz, CDCl3, δ ppm): 147.8, 143.9, 139.1, 135.8, 133.7, 133.5, 131.5, 131.1, 130.2, 129.8, 129.6, 128.4, 128.1, 127.6, 121.3, 107.5, 30.0, 21.6, 21.2.
19F NMR (376 MHz, CDCl3, δ ppm): δ -73.9 (s, 3F).
HRMS (ESI) calculated value C24H22F3NO5S 2+ Na 548.0789, actual value 548.0792.
Example 13
3g：
FIG. 14
In a 25 mL reactor under nitrogen atmosphere, diacetonitrile palladium dichloride (5.0 mg, 0.02mmol) and potassium phosphate (85.0 mg, 0.40 mmol) were added, and the substrates 1a (59.8 mg, 0.20 mmol) and 2e (38.0 mg, 0.24 mmol) were weighed into the reactor, and 1, 4-dioxane (2 mL) was added. Heating the reaction system to 50oC, reacting for 0.5 h. After the TLC detection reaction, the system was cooled to room temperature. Extraction with ethyl acetate, washing three times with 30mL of saturated sodium chloride solution, drying over anhydrous sodium sulfate, spin-drying over silica gel, and column chromatography gave 3g (58%) of a pale yellow liquid.1H NMR (400 MHz, CDCl3, δ ppm):7.54 (d, J = 7.6 Hz, 2H), 7.27 (d, J = 8 Hz, 2H), 7.12 (d, J = 8 Hz, 2H), 7.06-6.98 (m, 2H), 6.82 (d, J = 7.6 Hz, 2H), 6.78-6.70 (m, 2H), 4.48-4.41 (m, 1H), 3.25 (d, J = 7.2 Hz, 2H), 2.44 (s, 3H), 2.33 (s, 3H).
13C NMR (100 MHz, CDCl3, δ ppm): 161.5 (dd, J = 236.3, 11.8 Hz), 160.6 (dd, J = 234.9, 11.5 Hz), 143.8, 139.0, 135.9, 133.8, 130.7 (dd, J = 9.4, 6.3 Hz,), 130.6, 130.2, 129.8, 129.6, 127.5, 123.4 (dd, J = 15.8, 3.8 Hz), 111.0 (dd, J = 20.8, 3.8 Hz), 108.8, 103.6 (t, J = 25.5 Hz), 28.5 (d, J = 2.8 Hz), 21.6, 21.2.
19F NMR (376 MHz, CDCl3, δ ppm): δ-113.3 (s, 1F), -114.4 (s, 1F).
HRMS (ESI) calculated value C23H21F2NO2S + Na 436.1159, actual value 436.1160.
Example 14
3h：
FIG. 15 shows a schematic view of a
In a 25 mL reactor under nitrogen atmosphere, diacetonitrile palladium dichloride (5.0 mg, 0.02mmol) and potassium phosphate (85.0 mg, 0.40 mmol) were added, and the substrates 1a (59.8 mg, 0.20 mmol) and 2f (46.0 mg, 0.24 mmol) were weighed into the reactor, and 1, 4-dioxane (2 mL) was added. Heating the reaction system to 50oC, reacting for 1 h. After the TLC detection reaction, the system was cooled to room temperature. Extraction with ethyl acetate, washing with 30mL of saturated sodium chloride solution three times, drying over anhydrous sodium sulfate, spin-drying on silica gel, and column chromatography gave a pale yellow liquid for 3h (50%).1H NMR (400 MHz, CDCl3, δ ppm):7.54 (d, J = 8 Hz, 2H), 7.38 (d, J = 7.6 Hz, 1H), 7.28 (d, J =8.4 Hz, 2H), 7.18-7.10 (m, 4H), 6.82(d, J = 8 Hz, 2H), 4.40-4.32 (m, 1H), 3.35 (d, J= 7.2 Hz, 2H), 2.44 (s, 3H), 2.34 (s, 3H).
13C NMR (100 MHz, CDCl3, δ ppm): 149.8, 147.9, 144.0, 140.8, 139.3, 135.6, 133.8, 133.5, 131.9,130.3, 129.7, 129.6, 127.5, 123.1, 106.2, 32.7, 21.7, 21.3.
HRMS (ESI) calculated value C22H20Cl2N2O2S + Na 469.0520, actual value 469.0522.
Example 15
3i：
FIG. 16
In a 25 mL reactor under nitrogen atmosphere, diacetonitrile palladium dichloride (5.0 mg, 0.02mmol) and potassium phosphate (85.0 mg, 0.40 mmol) were added, and substrate 1a (59.8 mg, 0.20 mmol) and 2g (39.0 mg, 0.24 mmol) were weighed into the reactor, and 1, 4-dioxane (2 mL) was added. Heating the reaction system to 50oC, reacting for 5 hours. After the TLC detection reaction, the system was cooled to room temperature. Extraction with ethyl acetate, washing three times with 30mL of saturated sodium chloride solution, drying over anhydrous sodium sulfate, spin-drying on silica gel, and column chromatography gave 3i (45%) as a pale yellow liquid.1H NMR (400 MHz, CDCl3, δ ppm):7.57 (d, J = 7.6 Hz, 2H), 7.45 (d, J = 7.6 Hz, 1H), 7.38 (d, J = 7.6 Hz, 1H), 7.27 (d, J = 8 Hz, 2H), 7.22-7.18 (m, 2H), 7.15 (d, J = 8.8 Hz, 3H), 6.86 (d, J = 7.2 Hz, 2H), 6.25 (s, 1H), 4.56-4.49 (m, 1H), 3.43 (d, J = 7.2 Hz, 2H), 2.44 (s, 3H), 2.35 (s, 3H).
13C NMR (100 MHz, CDCl3, δ ppm): 157.7, 154.7, 143.9, 139.2, 135.9, 133.7, 131.5, 130.2, 129.9,129.6, 128.7, 127.5, 123.3, 122.5, 120.3, 110.8, 106.0, 102.3, 29.1, 21.7, 21.3.
HRMS (ESI) calculated value C25H23NO3S + Na 440.1296, actual value 440.1298.
Example 16
3j：
FIG. 17
In a 25 mL reactor under nitrogen atmosphere, diacetonitrile palladium dichloride (5.0 mg, 0.02mmol) and potassium phosphate (85.0 mg, 0.40 mmol) were added, and substrate 1a (59.8 mg, 0.20 mmol) and 2h (56.0 mg, 0.24 mmol) were weighed into the reactor, and 1, 4-dioxane (2 mL) was added. Heating the reaction system to 50oC, reacting for 1.5 h. After the TLC detection reaction, the system was cooled to room temperature. Extraction with ethyl acetate, washing three times with 30mL of saturated sodium chloride solution, drying over anhydrous sodium sulfate, spin-drying over silica gel, and column chromatography gave 3j (79%) as a pale yellow liquid.1H NMR (400 MHz, CDCl3, δ ppm):7.58 (d, J =7.6 Hz, 2H), 7.48 (d, J = 7.6 Hz, 2H), 7.43 (d, J =7.6 Hz, 2H), 7.38 (d, J = 7.6 Hz, 2H), 7.29 (d, J = 8 Hz, 2H), 7.15 (d, J = 8.8 Hz, 3H), 7.09 (d, J = 15.2 Hz, 2H), 6.86 (d, J = 8 Hz, 2H), 4.58-4.51 (m, 1H), 3.33 (d, J = 7.2 Hz, 2H), 2.45 (s, 3H), 2.33 (s, 3H).
13C NMR (100 MHz, CDCl3, δ ppm): 143.8, 140.2, 139.4, 139.0, 137.8, 136.0, 133.9, 133.2, 130.2, 130.1, 129.9, 129.6, 128.9, 128.8, 128.2, 127.5, 126.9, 110.5, 35.7, 21.7, 21.2.
HRMS (ESI) calculated value C29H26ClNO2S + Na 510.1270, actual value 510.1273.
Example 17
3k：
FIG. 18
In a 25 mL reactor under nitrogen atmosphere, diacetonitrile palladium dichloride (5.0 mg, 0.02mmol) and potassium phosphate (85.0 mg, 0.40 mmol) were added, and the substrates 1a (59.8 mg, 0.20 mmol) and 2i (48.0 mg, 0.24 mmol) were weighed into the reactor, and 1, 4-dioxane (2 mL) was added. Heating the reaction system to 50oC, reacting for 4.5 h. After the TLC detection reaction, the system was cooled to room temperature. Extraction with ethyl acetate, washing three times with 30mL of saturated sodium chloride solution, drying over anhydrous sodium sulfate, spin-drying over silica gel, and column chromatography gave 3k (35%) as a pale yellow liquid.1H NMR (400 MHz, CDCl3, δ ppm):7.55 (d, J = 7.6 Hz, 2H), 7.49 (d, J = 7.6 Hz, 1H), 7.27 (s, 1H), 7.19 (t, J = 7.6Hz, 1H), 7.13-7.02 (m, 6H), 6.84 (d, J=8 Hz, 2H), 4.52-4.45 (m, 1H), 3.38 (d, J=6.8 Hz, 2H), 2.43 (s, 3H), 2.33(s, 3H).
13C NMR (100 MHz, CDCl3, δ ppm): 143.8, 139.8, 139.0, 135.9, 133.9, 132.7, 130.9, 130.2, 130.1, 130.0, 129.6, 127.8, 127.5, 127.5, 124.5, 108.9, 36.3, 21.6, 21.2.
HRMS (ESI) calculated value C23H22BrNO2S + Na 478.0452, actual value 478.0453.
Example 18
3l：
FIG. 19
In a 25 mL reactor under nitrogen atmosphere, diacetonitrile palladium dichloride (5.0 mg, 0.02mmol) and potassium phosphate (85.0 mg, 0.40 mmol) were added, and the substrates 1a (59.8 mg, 0.20 mmol) and 2j (40.0 mg, 0.24 mmol) were weighed into the reactor, and 1, 4-dioxane (2 mL) was added. Heating the reaction system to 50oC, reacting for 1 h.After the TLC detection reaction, the system was cooled to room temperature. Extraction with ethyl acetate, washing three times with 30mL of saturated sodium chloride solution, drying over anhydrous sodium sulfate, spin-drying over silica gel, and column chromatography gave 3l (31%) of a pale yellow liquid.1H NMR (400 MHz, CDCl3, δ ppm):8.04 (d, J = 3.6 Hz, 1H), 7.94 (s, 1H), 7.57 (d, J = 8 Hz, 2H), 7.42 (d, J = 4.8 Hz, 2H), 7.30 (d, J = 8 Hz, 2H), 7.13 (d, J = 7.6 Hz, 2H), 7.11 (d, J=9.2 Hz, 1H), 6.84 (d, J =8 Hz, 2H), 4.51-4.44 (m, 1H), 3.39 (d, J = 7.2 Hz, 2H), 2.45 (s, 3H), 2.33 (s, 3H).
13C NMR (100 MHz, CDCl3, δ ppm): 148.3, 144.0, 142.8,139.2, 135.7, 134.6, 133.6, 131.3,130.3, 129.8, 129.7, 129.3, 127.5, 123.1, 121.3, 108.7, 35.6, 21.7, 21.2.
HRMS (ESI) calculated value C23H22N2O4S + Na 445.1198, actual value 445.1201.
Example 19
3m：
FIG. 20
In a 25 mL reactor under nitrogen atmosphere, diacetonitrile palladium dichloride (5.0 mg, 0.02mmol) and potassium phosphate (85.0 mg, 0.40 mmol) were added, and the substrate 1a (59.8 mg, 0.20 mmol) and 2k (35.0 mg, 0.24 mmol) were weighed into the reactor, and 1, 4-dioxane (2 mL) was added. Heating the reaction system to 50oC, reacting for 2 h. After the TLC detection reaction, the system was cooled to room temperature. Extraction with ethyl acetate, washing three times with 30mL of saturated sodium chloride solution, drying over anhydrous sodium sulfate, spin-drying over silica gel, and column chromatography gave a pale yellow liquid of 3m (25%).1H NMR (400 MHz, CDCl3, δ ppm):7.56 (d, J = 7.6 Hz, 2H), 7.46 (d, J = 7.2 Hz, 1H), 7.37-7.30 (m, 5H), 7.14 (d, J = 8 Hz, 2H), 7.08 (d, J = 14 Hz, 1H), 6.84 (d, J = 8 Hz, 2H), 4.48-4.41 (m, 1H), 3.32 (d, J = 7.2 Hz, 2H), 2.46 (s, 3H), 2.34 (s, 3H).
13C NMR (100 MHz, CDCl3, δ ppm): 144.1, 142.2, 139.2, 135.7, 133.6, 133.0, 131.7, 131.2,130.2, 130.0, 129.8, 129.7, 129.2, 127.5, 119.0, 112.3, 108.7, 35.6, 21.7, 21.3.
HRMS (ESI) calculated value C24H22N2O2S + Na 425.1300, actual value 425.1304.
Example 20
3n：
FIG. 21
In a 25 mL reactor under nitrogen atmosphere, diacetonitrile palladium dichloride (5.0 mg, 0.02mmol) and potassium phosphate (85.0 mg, 0.40 mmol) were added, and substrate 1a (59.8 mg, 0.20 mmol) and 2l (38.0 mg, 0.24 mmol) were weighed into the reactor, and 1, 4-dioxane (2 mL) was added. Heating the reaction system to 50oC, reacting for 2 h. After the TLC detection reaction, the system was cooled to room temperature. Extraction with ethyl acetate, washing three times with 30mL of saturated sodium chloride solution, drying over anhydrous sodium sulfate, spin-drying over silica gel, and column chromatography gave 3n (66%) as a pale yellow liquid.1H NMR (400 MHz, CDCl3, δ ppm):7.55 (d, J = 7.6 Hz, 2H), 7.28 (d, J = 7.6 Hz, 2H), 7.20 (d, J = 7.2 Hz, 2H), 7.12 (d, J = 7.6 Hz, 2H), 7.04 (d, J = 14 Hz, 1H), 6.99 (d, J = 7.6 Hz, 2H), 6.83 (d, J = 7.2 Hz, 2H), 4.50-4.43 (m, 1H), 3.24 (d, J = 7.2 Hz, 2H), 2.45 (s, 3H), 2.33 (s, 3H).
13C NMR (100 MHz, CDCl3, δ ppm): 143.8, 139.1, 139.0, 135.9, 133.8, 131.8, 130.4, 130.2,129.8, 129.6, 129.6, 128.4, 127.5, 110.2, 35.4, 21.7, 21.3.
HRMS (ESI) calculated value C23H22ClNO2S + Na 434.0957, actual value 434.0954.

Claims (7)

1. A selective addition method of dienamine and phenylboronic acid controlled by small steric hindrance is characterized in that 4-methyl-N- (propyl 1, 2-diene-1-yl) -N- (p-tolyl) benzene sulfonamide compounds and phenylboronic acid are used as reaction substrates, and (E) -N- (3- (2-phenyl) prop-1-ene-1-yl) -4-methyl-N- (p-tolyl) benzenesulfonamide derivatives; the reaction equation is shown below;
Figure RE-231594DEST_PATH_IMAGE001
wherein R is1Is an aryl group; r is alkyl, ester group, halogen, heterocycle and aryl.
2. The synthetic method of claim 1 wherein the palladium catalyst is PdCl2(dppe)、PdCl2(PPh3)2、Pd(MeCN)2Cl2(ii) a The catalyst was used in an amount of 10 mol% equivalent based on the amount of the compound 1.
3. The synthetic process for the selective addition of a dienamine with phenylboronic acid with small steric hindrance control of claim 1 wherein the reaction solvent system is toluene, tetrahydrofuran, 1, 4-dioxane.
4. The synthetic method for preparing a selective addition of a dienamine with small steric hindrance control and phenylboronic acid according to claim 1, wherein the synthetic reaction is at 50%oAnd C, performing.
5. The synthetic method for preparing selective addition of dienamine with small steric hindrance control and phenylboronic acid according to claim 1 wherein the reaction time is 0.5 to 5 hours.
6. The synthetic method of claim 1 for making a selective addition of a small sterically hindered controlled dienamine to phenylboronic acid wherein the base is cesium carbonate (Cs)2CO3) Cesium fluoride (CsF), potassium phosphate (K)3PO4) (ii) a The amount of the base used was 2.0 equivalents based on the amount of compound 1 used.
7. The (E) -N- (3- (2-phenyl) prop-1-en-1-yl) -4-methyl-N- (p-tolyl) benzenesulfonamide derivative prepared through the process as shown in claim 1.
CN202110300752.XA 2021-03-22 2021-03-22 Selective addition method of dienamine and phenylboronic acid controlled by small steric hindrance Expired - Fee Related CN113214119B (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105348321A (en) * 2015-11-11 2016-02-24 南京师范大学 Synthesis method of alpha,alpha-difluoromethylene vinyl phosphonate
CN108178770A (en) * 2017-12-11 2018-06-19 华南理工大学 A kind of method for synthesizing alpha-amido boron compound
CN109336792A (en) * 2018-11-28 2019-02-15 山东理工大学 A kind of 4- Methyl-N-phenyl-N-(2- phenyl allyl) benzenesulfonamides synthetic method

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105348321A (en) * 2015-11-11 2016-02-24 南京师范大学 Synthesis method of alpha,alpha-difluoromethylene vinyl phosphonate
CN108178770A (en) * 2017-12-11 2018-06-19 华南理工大学 A kind of method for synthesizing alpha-amido boron compound
CN109336792A (en) * 2018-11-28 2019-02-15 山东理工大学 A kind of 4- Methyl-N-phenyl-N-(2- phenyl allyl) benzenesulfonamides synthetic method

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
RACHA ABED ALI ABDINE: "Hydroarylation of N-Allenyl Derivatives Catalyzed by Copper", 《EUROPEAN JOURNAL OF ORGANIC CHEMISTRY》 *
VALENTINA PIROVANO: "Gold-Catalyzed Cascade Reactions of 4H-Furo[3,2-b]indoles with Allenamides: Synthesis of Indolin-3-one Derivatives", 《JOURNAL OF ORGANIC CHEMISTRY》 *

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