CN115477631A - Synthesis method of compound containing dimethyl enol group - Google Patents

Synthesis method of compound containing dimethyl enol group Download PDF

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CN115477631A
CN115477631A CN202211226668.9A CN202211226668A CN115477631A CN 115477631 A CN115477631 A CN 115477631A CN 202211226668 A CN202211226668 A CN 202211226668A CN 115477631 A CN115477631 A CN 115477631A
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CN115477631B (en
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江世智
雷婷
吴珍珍
杨斌全
鹿贵东
白梦娇
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Dali University
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    • 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
    • C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
    • C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
    • C07D311/16—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 7
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    • C07C41/01—Preparation of ethers
    • C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
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    • C07C45/64—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of functional groups containing oxygen only in singly bound form
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    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
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Abstract

The invention discloses a composition containingThe technical field of synthesis of compounds containing methyl enol groups, in particular to a synthesis method of compounds containing dimethyl enol groups; under the protection of nitrogen, adding magnetons and a condenser tube into a double-neck round-bottom flask, and adding a brominated substrate 1, bis (tri-tert-butylphosphine) palladium (0), toluene, triethylamine and an olefin compound 2; then the reaction bottle is sealed and put in an oil bath at 90 ℃; after completion of the reaction (monitored by TLC, about 12 min), the reaction mixture was cooled to room temperature and NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; the insoluble solid was removed by transferring through a short column of silica gel with ethyl acetate and washing with ethyl acetate; the filtrate was diluted with ethyl acetate and extracted 3 times with water; the synthesis route of the patent is simple, the raw materials are simple and easy to obtain, the operation is simple and convenient, the catalyst is less in use amount, cheap and easy to obtain, and the derivative yield is good.

Description

Synthesis method of compound containing dimethyl enol group
Technical Field
The invention relates to the technical field of synthesis of compounds containing a dimethyl enol group, in particular to a synthesis method of compounds containing the dimethyl enol group.
Background
At present: full synthetic work on (E) -Suberenol was reported (J.Am.chem.Soc., 2018,140 (8): 3156-3169.; https:// doi.org/10.1021/jacs.8b00665). For the synthesis of Suberenol, guthertz group starts from 7-methoxycoumarin (6), firstly, coumarate (7) is obtained through cracking, then, iodine atoms are introduced to obtain a compound (10), cyclization is carried out to obtain 6-iodo-7-methoxycoumarin (11), 6-iodo-7-methoxycoumarin (11) and 2-methyl-3-butyn-2-ol (12) generate 6-alkynyl coumarin (13) under the catalysis of Pd/Cu, and finally, (E) -Suberenol (5) is obtained through reduction reaction catalyzed by [ Cp RuCl ] 4. This synthetic route uses highly active iodides. In addition, 6-iodo-7-methoxycoumarin (11) is difficult to obtain and the conversion rate of the reaction is very low, so that 7-hydroxycoumarin with very high structural similarity is required to be used to obtain the required iodide, and the yield is low; the synthetic routes of Guthertz group are relatively long and low in total yield, and the reports of mild and efficient synthesis of enol compounds by using simple raw materials are still few. Such as the use of high-activity iodides which require severe reaction conditions, high temperatures, and are difficult to prepare, and the like. In addition, the existing route has the disadvantages of complex steps, non-universal starting materials, long reaction time, poor atom economy, high preparation cost and low total yield. In view of this, it is very important to develop a simple and economical synthesis method to synthesize various dimethyl enol compounds. .
Based on this, the present invention has devised a synthetic method of a compound containing a dimethyl enol group to solve the above-mentioned problems.
Disclosure of Invention
The present invention has been made to solve the above-mentioned problems occurring in the prior art, and an object of the present invention is to provide a method for synthesizing a compound having a dimethyl enol group.
In order to achieve the purpose, the invention provides the following technical scheme: a method for synthesizing a compound containing a dimethyl enol group, the method comprising the steps of:
the method comprises the following steps: preparation of E-suberenol (5)
Figure BDA0003880053050000021
Under the protection of nitrogen, adding magnetons and a condenser tube into a double-neck round-bottom flask, and adding a brominated substrate 1, bis (tri-tert-butylphosphine) palladium (0), toluene, triethylamine and an olefin compound 2; then the reaction flask is sealed and placed in an oil bath at 90 ℃; after completion of the reaction (monitored by TLC, about 12 min), the reaction mixture was cooled to room temperature and NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; the insoluble solid was removed by transferring through a short column of silica gel with ethyl acetate and washing with ethyl acetate; diluting the filtrate with ethyl acetate, extracting with water for 3 times, and extracting with saturated sodium chloride for 1 time; the combined organic layers were washed with anhydrous Na 2 SO 4 Drying, filtering the organic phase, and concentrating to obtain a crude product; carrying out wet sample loading column chromatography purification to obtain a compound E-suberenol;
step two: (E) Preparation of 2-methyl-4- (2, 4, 6-trimethoxyphenyl) but-3-en-2-ol (5-1):
adding magnet into a double-neck round-bottom flask under the protection of nitrogenA condenser tube, 2-bromo-1, 3, 5-trimethoxybenzene, bis (tri-tert-butylphosphine) palladium (0) and toluene were combined to fill a two-necked round-bottomed flask, et 3 N, olefin compound 2 (1, 1-dimethylallyl alcohol); then the reaction bottle is sealed and placed in an oil bath at 100 ℃; after completion of the reaction (monitored by TLC, about 1 hour), the reaction mixture was cooled to room temperature and 1mL of saturated NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; then filtering the reaction crude product through diatomite and washing the reaction crude product with ethyl acetate; the filtrate was diluted with ethyl acetate and extracted with water and brine; the combined organic phases were treated with anhydrous Na 2 SO 4 Drying, filtering the organic phase and concentrating in vacuo at 30 ℃ to provide a crude product; purifying by flash column chromatography to obtain target compound;
step three: (E) Preparation of (E) -4- (4- (ethoxymethoxy) phenyl) -2-methylbutyl-3-en-2-ol (5-2):
under the protection of nitrogen, adding magnetons, a condenser, 1-bromo-4- (ethoxymethoxymethyl) benzene, bis (tri-tert-butylphosphine) palladium (0), toluene and Et into a double-neck round-bottom flask 3 N, olefin compound 2 (1, 1-dimethylallyl alcohol); then the reaction bottle is sealed and placed in an oil bath at 100 ℃; after completion of the reaction (monitored by TLC, about 30 min), the reaction mixture was cooled to room temperature and 1mL of saturated NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; then filtering the reaction crude product through diatomite and washing the reaction crude product with ethyl acetate; the filtrate was diluted with ethyl acetate and extracted with water and brine; the combined organic phases were treated with anhydrous Na 2 SO 4 Drying, filtering the organic phase and concentrating in vacuo at 30 ℃ to provide a crude product; purifying by flash column chromatography to obtain target compound;
step four: (E) Preparation of (E) -1- (2-hydroxy-5- (3-hydroxy-3-methylbut-1-en-1-yl) -4-methoxyphenyl) ethan-1-one (5-3):
adding magnetons and a condenser, 1- (5-bromo-2-hydroxy-4-methoxymethylphenyl) ethane-1-one, bis (tri-tert-butylphosphine) palladium (0), toluene and Et into a double-neck round-bottom flask under the protection of nitrogen 3 N, olefin compound 2 (1, 1-dimethylallyl alcohol); the reaction flask was then sealed and placed in a 100 ℃ oil bathThe preparation method comprises the following steps of (1) performing; after completion of the reaction (monitored by TLC, about 1 hour), the reaction mixture was cooled to room temperature and 1mL of saturated NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; then filtering the reaction crude product through diatomite and washing the reaction crude product with ethyl acetate; the filtrate was diluted with ethyl acetate and extracted with water and brine; the combined organic phases were treated with anhydrous Na 2 SO 4 Drying, filtering the organic phase and concentrating in vacuo at 30 ℃ to provide a crude product; purifying by flash column chromatography to obtain target compound;
step five: (E) Preparation of (E) -4- (benzofuran-5-yl) -2-methylbut-3-en-2-ol (5-4):
under the protection of nitrogen, adding magnetons, a condenser, 5-bromobenzofuran, bis (tri-tert-butylphosphine) palladium (0), toluene and Et into a double-neck round-bottom flask 3 N, olefin compound 2 (1, 1-dimethylallyl alcohol); then the reaction bottle is sealed and placed in an oil bath at 100 ℃; after 30 minutes of reaction, the reaction mixture was cooled to room temperature and 1mL of saturated NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; then filtering the reaction crude product through diatomite and washing the reaction crude product with ethyl acetate; the filtrate was diluted with ethyl acetate and extracted with water and brine; the combined organic phases were treated with anhydrous Na 2 SO 4 Drying, filtering the organic phase and concentrating in vacuo at 30 ℃ to provide a crude product; purifying by flash column chromatography to obtain target compound;
step six: (E) Preparation of (E) -4- (1H-indol-5-yl) -2-methylbut-3-en-2-ol (5-5):
adding magnetons and a condenser, 5-bromo-1H-indole, bis (tri-tert-butylphosphine) palladium (0), toluene, et3N (82. Mu.L, 0.6mmol, 1.5eq.), and an olefin compound 2 (1, 1-dimethylallyl alcohol) into a double-neck round-bottom flask under the protection of nitrogen; then the reaction bottle is sealed and placed in an oil bath at 100 ℃; after 30 minutes of reaction, the reaction mixture was cooled to room temperature and 1mL of saturated NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; then filtering the reaction crude product through diatomite, and washing the reaction crude product with ethyl acetate; the filtrate was diluted with ethyl acetate and extracted with water and brine; the combined organic phases were treated with anhydrous Na 2 SO 4 Drying, filtering the organic phase, andconcentrating in vacuo at 30 ℃ to provide a crude product; purifying by flash column chromatography to obtain target compound;
step seven: (E) Preparation of-2-methyl-4- (thiophen-3-yl) but-3-en-2-ol (5-6):
under the protection of nitrogen, adding magnetons and a condenser, 3-bromothiophene, bis (tri-tert-butylphosphine) palladium (0), toluene and Et into a double-neck round-bottom flask 3 N, olefin compound 2 (1, 1-dimethylallyl alcohol); then the reaction bottle is sealed and placed in an oil bath at 100 ℃; after 30 minutes of reaction, the reaction mixture was cooled to room temperature and 1mL of saturated NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; then filtering the reaction crude product through diatomite and washing the reaction crude product with ethyl acetate; the filtrate was diluted with ethyl acetate and extracted with water and brine; the combined organic phases were treated with anhydrous Na 2 SO 4 Drying, filtering the organic phase and concentrating in vacuo at 30 ℃ to provide a crude product; after purification by flash column chromatography, the target compound was obtained.
As a further embodiment of the present invention, the saturated solution of sodium bicarbonate may be replaced with potassium bicarbonate, sodium carbonate, potassium carbonate, calcium carbonate, sodium monohydrogen phosphate, sodium dihydrogen phosphate, potassium monohydrogen phosphate, potassium dihydrogen phosphate, potassium phosphate, sodium phosphate, or calcium phosphate.
As a further embodiment of the present invention, the tri-tert-butylphosphine may be replaced by triphenylphosphine, trimethylphosphine, tris (o-methylphenyl) phosphorus, tricyclohexylphosphine fluoborate, tri-N-butylphosphine, 4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene, bis (2-diphenylphosphine) ether, tris (2-furyl) phosphine, tri-tert-butylphosphine tetrafluoroborate, 1, 2-bis (diphenylphosphine) ethane, 1, 3-bis (diphenylphosphine) propane, 1, 4-bis (diphenylphosphine) butane, 2- (di-tert-butylphosphine) biphenyl, 2- (dicyclohexylphosphino) biphenyl, 2-dicyclohexylphosphino-2 ',6' -dimethoxybiphenyl, 2-dicyclohexylphosphino-2 ' - (N, N-dimethylamine) -biphenyl, 2-dicyclohexylphosphine-2 ',4',6' -triisopropylbiphenyl, N-butylbis (1-adamantyl) phosphine, 1' -bis (diisopropylphosphine) ferrocene, R- (+) -1,1' -binaphthyl-2, 2' -bisdiphenylphosphine, 1' -bi-2-naphthol, 5' -bis (diphenylphosphoryl) -4,4' -di-1, 3-biphenyl, bisdiphenylphosphorylbiphenyl, bis (2-diphenylphosphinyl) ether, 1-bis (di-tert-butylphosphino) -ferrocene, 2-di-tert-butylphosphino-2 ',4',6' -triisopropylbiphenyl, tetratriphenylphosphine palladium chloride, bis (tri-tert-butylphosphine) palladium, [1,1' -bis (di-tert-butylphosphine) ferrocene ] palladium (II) dichloride or without addition of a ligand.
As a further embodiment of the present invention, triethylamine may be replaced with tri-N-propylamine, N-diisopropylethylamine, N-diethylaniline, tri-N-octylamine, N-cyclohexylmethylamine, pyridine, 4-dimethylaminopyridine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, 1, 4-diazabicyclo [2.2.2] octane, tetrabutylammonium chloride, tetrabutylammonium bromide, triethylenediamine, N-methyldicyclohexylamine, tetrabutylammonium hydroxide, potassium acetate, sodium bicarbonate, potassium bicarbonate, ammonium bicarbonate, sodium carbonate, potassium carbonate, ammonium carbonate, calcium carbonate, cesium carbonate, sodium monohydrogen phosphate, sodium dihydrogen phosphate, potassium monohydrogen phosphate, potassium dihydrogen phosphate, potassium phosphate, sodium phosphate, calcium phosphate, or no base addition.
In a further embodiment of the present invention, the toluene may be substituted for tetrahydrofuran, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone, benzene, xylene, 1, 4-dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, 1, 2-dichloroethane, polyethylene glycol, acetonitrile, chlorobenzene, dimethylsulfoxide, or no solvent is added.
As a further scheme of the invention, the reaction temperature in the synthesis process is between 40 and 145 ℃.
As a further scheme of the present invention, the brominated substrate is:
Figure BDA0003880053050000061
or other similar brominated substrates.
As a further embodiment of the present invention, the olefinic compound is:
Figure BDA0003880053050000062
or other olefinic compounds.
Compared with the prior art, the invention has the beneficial effects that:
1. the synthetic route of the patent takes a bromo-substrate which is simple and easy to prepare as an initial raw material, and obtains the dimethyl enol compound with higher yield, and the compound is firstly synthesized. Different bromine substituted compounds are used, and are subjected to reaction coupling with 2-methylbutene-2-alcohol through a Heck reaction catalyzed by palladium so as to obtain the enol compound with medium to high yield, the patent route overcomes the problems of environmental hazard, complex operation, low yield and the like, simultaneously avoids the use of high-activity iodide which is difficult to prepare, and the enol compound is obtained with high to medium yield by using different bromine substituted compounds; generally, the method has the advantages of simple synthetic route, simple and easily-obtained raw materials, simple and convenient operation, small catalyst consumption, low cost, easy obtaining and good derivative yield, and not only provides a new method for synthesizing the enol compound, but also provides more possibilities for large-scale production of products and production efficiency improvement. The prepared dimethyl enol compound is a compound with potential physiological activity; meanwhile, the use of high-activity iodide which is difficult to prepare is avoided; an electron-rich, large steric hindrance deactivated bromo compound is used as an intermediate; solves the problems of low purity, complex operation, low yield and mass production in the prior art; the atom economy of the reaction is improved; provides a preparation method of enol compounds with stable process, simple and convenient operation and high synthesis efficiency.
2. The synthesis route of the patent is simple, the raw materials are simple and easy to obtain, the operation is simple and convenient, the catalyst is low in usage amount and cheap and easy to obtain, and the derivative has high yield, so that a new method is provided for the synthesis of the dimethyl enol compound, and more possibilities are provided for the large-scale production of products and the improvement of the production efficiency.
Drawings
FIG. 1 is a schematic diagram of the NMR spectrum of E-subeenol (5) according to the invention;
FIG. 2 is a schematic nuclear magnetic resonance carbon spectrum of E-subeenol (5) according to the present invention;
FIG. 3 is a schematic diagram of the NMR spectrum of E-subeenol (5) derivative 1 of the present invention;
FIG. 4 is a schematic nuclear magnetic resonance carbon spectrum of the E-suberenol (5) derivative 1 of the present invention;
FIG. 5 is a schematic diagram of the NMR spectrum of E-subeenol (5) derivative 2 of the present invention;
FIG. 6 is a schematic nuclear magnetic resonance carbon spectrum of E-suberenol (5) derivative 2 of the present invention;
FIG. 7 is a schematic diagram of the NMR spectrum of E-suberenol (5) derivative 3 of the present invention;
FIG. 8 is a schematic nuclear magnetic resonance carbon spectrum of E-suberenol (5) derivative 3 of the present invention;
FIG. 9 is a schematic nuclear magnetic resonance hydrogen spectrum of E-suberenol (5) derivative 4 of the present invention;
FIG. 10 is a schematic nuclear magnetic resonance carbon spectrum of E-suberenol (5) derivative 4 of the present invention;
FIG. 11 is a schematic nuclear magnetic resonance hydrogen spectrum of E-suberenol (5) derivative 5 of the present invention;
FIG. 12 is a schematic nuclear magnetic resonance carbon spectrum of E-suberenol (5) derivative 5 of the present invention;
FIG. 13 is a schematic nuclear magnetic resonance hydrogen spectrum of E-suberenol (5) derivative 6 of the present invention;
FIG. 14 is a schematic nuclear magnetic resonance carbon spectrum of E-suberenol (5) derivative 6 of the present invention.
Detailed Description
Referring to fig. 1-14, the present invention provides a technical solution: a method for synthesizing a compound containing a dimethyl enol group, the method comprising the steps of:
the method comprises the following steps: : preparation of E-suberenol (5)
Figure BDA0003880053050000081
Under nitrogen protection, 6-bromo-7-methoxycoumarin (1.02g, 4.0mmol,1.0 eq.) bis (tri-tert-butylphosphine) palladium (0) (164mg, 0.032mmol, 0.08eq.) toluene (15 mL), triethylamine (834. Mu.L, 6.0) were added to a two-necked round-bottomed flask with a magnetic particle and a condenser tubemmol,1.5 eq.), 1-dimethylallyl alcohol (1.88ml, 18.0mmol, 4.5eq.); then the reaction flask is sealed and placed in an oil bath at 90 ℃; after completion of the reaction (monitored by TLC, about 12 min), the reaction mixture was cooled to room temperature and NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; the insoluble solid was removed by transferring through a short column of silica gel with ethyl acetate and washing with ethyl acetate (100 mL); diluting the filtrate with ethyl acetate, extracting with water for 3 times, and extracting with saturated sodium chloride for 1 time; the combined organic layers were washed with anhydrous Na 2 SO 4 Drying, filtering the organic phase, and concentrating to obtain a crude product; after wet column chromatography (eluent, PE: EA =8: (1.02g, 98% yield);
structural characterization data for compound E-suberenol:
1 H NMR(400MHz,CDCl 3 )δ7.63(d,1H,J＝9.4Hz),7.48(s,1H),6.85(d,1H,J＝16.2Hz),6.78(s,1H),6.36(d,1H,J＝16.2Hz),6.26(d,1H,J＝9.4Hz),3.90(s,3H),1.44(s,6H)；
13 C NMR(100MHz,CDCl 3 )δ161.20,159.93,155.11,143.49,139.20,125.33,123.78,119.74,113.39,112.20,98.94,71.26,56.00,29.91；
IR(KBr):3838.15,3732.92,3433.47,2932.10,2345.14,1728.08,1611.93,1356.06,1210.07,1020.71,830.13,675.92cm -1 ；
HRMS(EI)calcd for C 15 H 16 O 4 [M+Na] + 283.0940,found 283.0941.
step two: (E) Preparation of 2-methyl-4- (2, 4, 6-trimethoxyphenyl) but-3-en-2-ol (5-1):
to a two-necked round bottom flask, under nitrogen protection, add magnetite plus condenser, 2-bromo-1, 3, 5-trimethoxybenzene (98.4mg, 0.4mmol, 1.0eq.), bis (tri-tert-butylphosphine) palladium (0) (16.4mg, 0.032mmol, 0.08eq.), and toluene (3 mL, 10min nitrogen sparge prior to addition) to fill the two-necked round bottom flask, et3N (82 μ L,0.6mmol, 1.5eq.), 1-dimethylallyl alcohol (184 μ L,1.8mmol, 4.5eq.); then the reaction bottle is sealed and placed in an oil bath at 100 ℃; after completion of the reaction (monitored by TLC, about 1 hour), the reaction mixture was cooledIt was cooled to room temperature and 1mL of saturated NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; the crude reaction product was then filtered through celite and washed with ethyl acetate (30 mL); the filtrate was diluted with ethyl acetate (50 mL) and extracted with water (2X 10 mL) and brine (10 mL); the combined organic phases were treated with anhydrous Na 2 SO 4 Drying, filtering the organic phase and concentrating in vacuo at 30 ℃ to provide a crude product; after purification by flash column chromatography (PE: EA =15, 1 to 2), the target compound (40.5 mg, yield 41%; starting material recovered, 49.2mg,50%; yield 91% based on starting material recovered);
(E) -2-methyl-4- (2, 4, 6-trimethoxyphenyl) but-3-en-2-ol structural data characterisation:
1 H NMR(400MHz,CDCl 3 )δ6.81(d,J＝16.5Hz,1H),6.70(d,J＝16.5Hz,1H),6.13(s,2H),3.82(s,6H),3.81(s,3H),1.42(s,7H)；
13 C NMR(100MHz,CDCl 3 )δ159.94,159.25,138.88,116.41,107.13,90.67,71.75,55.68,55.29,30.00；
IR(KBr):3881.16,3657.04,3509.77,3370.59,3315.668,3256.67,3000.69,2856.29,1614.78,1411.74,1240.71,1004.91,787.98,689.26,565.10cm -1 .
step three: (E) Preparation of (E) -4- (4- (ethoxymethoxy) phenyl) -2-methylbutyl-3-en-2-ol (5-2):
to a two-necked round bottom flask, under nitrogen protection, magnetite plus condenser tube, 1-bromo-4- (ethoxymethoxymethyl) benzene (92mg, 0.4mmol, 1.0eq.), bis (tri-tert-butylphosphine) palladium (0) (16.4mg, 0.032mmol, 0.08eq.), toluene (3 mL, 10min nitrogen sparge prior to addition), et3N (82. Mu.L, 0.6mmol, 1.5eq.), 1-dimethylallyl alcohol (184. Mu.L, 1.8mmol, 4.5eq.); then the reaction bottle is sealed and placed in an oil bath at 100 ℃; after completion of the reaction (monitored by TLC, about 30 min), the reaction mixture was cooled to room temperature and 1mL of saturated NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; the crude reaction product was then filtered through celite and washed with ethyl acetate (30 mL); the filtrate was diluted with ethyl acetate (50 mL) and extracted with water (2X 10 mL) and brine (10 mL); the organic phases are combinedWith anhydrous Na 2 SO 4 Drying, filtering the organic phase and concentrating in vacuo at 30 ℃ to provide a crude product; after purification by flash column chromatography (PE: EA =8 1 to 2), the target compound (74 mg, yield 80%, recovered starting material, 10.1mg,11%; yield 91% based on recovered starting material) was obtained;
(E) -4- (4- (ethoxymethoxy) phenyl) -2-methylbutyl-3-en-2-ol structural data characterisation:
1 H NMR(400MHz,CDCl 3 )δ7.31(d,J＝2.1Hz,1H),7.30(d,J＝2.1Hz,1H),7.00(d,J＝2.1Hz,1H),6.98(d,J＝2.1Hz,1H),6.53(d,J＝16.1Hz,1H),6.23(d,J＝16.1Hz,1H),5.22(s,2H),3.72(q,J＝7.1Hz,2H),1.41(s,6H),1.22(t,J＝7.1Hz,3H)；
13 C NMR(100MHz,CDCl 3 )δ156.83,135.83,130.67,127.50,125.74,116.32,93.10,71.05,64.24,29.93,15.13；
IR(KBr):3478.96,3380.26,3267.86,2869.52,1681.96,1619.20,1370.58,1295.80,1114.74,1079.85,856.23,701.95,573.31cm -1 .
step four: (E) Preparation of (E) -1- (2-hydroxy-5- (3-hydroxy-3-methylbut-1-en-1-yl) -4-methoxyphenyl) ethan-1-one (5-3):
to a two-necked round bottom flask, under nitrogen protection, magnetons and a condenser were added, 1- (5-bromo-2-hydroxy-4-methoxymethylbenzene) ethan-1 one (97.6mg, 0.4mmol, 1.0eq.), bis (tri-tert-butylphosphine) palladium (0) (16.4mg, 0.032mmol, 0.08eq.), toluene (3 mL, 10 minutes before addition by nitrogen bubbling), et3N (82. Mu.L, 0.6mmol, 1.5eq.), 1-dimethylallyl alcohol (184. Mu.L, 1.8mmol, 4.5eq.); then the reaction flask is sealed and placed in an oil bath at 100 ℃; after completion of the reaction (monitored by TLC, about 1 hour), the reaction mixture was cooled to room temperature and 1mL of saturated NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; the crude reaction product was then filtered through celite and washed with ethyl acetate (30 mL); the filtrate was diluted with ethyl acetate (50 mL) and extracted with water (2X 10 mL) and brine (10 mL); the combined organic phases were treated with anhydrous Na 2 SO 4 Drying, filtering the organic phase and concentrating in vacuo at 30 ℃ to provide a crude product; by speeding upAfter column chromatography purification (PE: EA =8 1 to 2), the target compound (45mg, 45%; starting material recovered, 52.7mg,54%; 99% yield based on starting material recovered) was obtained;
(E) -1- (2-hydroxy-5- (3-hydroxy-3-methylbut-1-en-1-yl) -4-methoxyphenyl) ethan-1-one structural data characterisation:
1 H NMR(400MHz,CDCl 3 )δ12.76(s,1H),7.73(s,1H),6.76(d,J＝16.2Hz,1H),6.41(s,1H),6.30(d,J＝16.2Hz,1H),3.88(s,3H),2.61(s,3H),1.45(s,6H)；
13 C NMR(100MHz,CDCl 3 )δ202.85,164.56,163.30,137.11,129.07,120.30,118.37,113.51,99.36,77.24,71.28,55.83,29.97,26.40；
IR(KBr):3464.50,2964.65,1616.85,1440.76,1379.93,1238.21,1183.45,1122.80,881.32,814.28,588.64,517.14cm -1 .
step five: (E) Preparation of (E) -4- (benzofuran-5-yl) -2-methylbut-3-en-2-ol (5-4):
to a two-necked round bottom flask, under nitrogen protection, magnetons and condenser tubes, 5-bromobenzofuran (78.4mg, 0.4mmol, 1.0eq.), bis (tri-tert-butylphosphine) palladium (0) (16.4mg, 0.032mmol, 0.08eq.), toluene (3 mL, 10min nitrogen sparge before addition), et3N (82. Mu.L, 0.6mmol, 1.5eq.), 1-dimethylallyl alcohol (184. Mu.L, 1.8mmol, 4.5eq.); then the reaction bottle is sealed and placed in an oil bath at 100 ℃; after 30 minutes of reaction, the reaction mixture was cooled to room temperature and 1mL of saturated NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; the crude reaction product was then filtered through celite and washed with ethyl acetate (30 mL); the filtrate was diluted with ethyl acetate (50 mL) and extracted with water (2X 10 mL) and brine (10 mL); the combined organic phases were treated with anhydrous Na 2 SO 4 Drying, filtering the organic phase and concentrating in vacuo at 30 ℃ to provide a crude product; after purification by flash column chromatography (PE: EA =8, 1 to 2), the target compound was obtained (72.9mg, 92% yield);
(E) -4- (benzofuran-5-yl) -2-methylbut-3-en-2-ol structural data characterisation:
1 H NMR(400MHz,CDCl 3 )δ7.60(d,J＝2.2Hz,1H),7.58(d,J＝1.7Hz,1H),7.44(d,J＝8.5Hz,1H),7.35(dd,J＝8.6,1.8Hz,1H),6.73(dd,J＝2.2,0.9Hz,1H),6.68(d,J＝16.1Hz,1H),6.34(d,J＝16.1Hz,1H),1.45(s,6H).
13 C NMR(100MHz,CDCl 3 )δ154.55,145.45,136.46,132.00,127.76,126.53,122.86,119.09,111.39,106.64,71.11,29.97；
IR(KBr):3818.95,3613.46,3548.05,3361.82,3224.16,2907.54,2711.24,2441.15,1943.73,1756.19,1550.36,1343.00,1063.84,779.27,685.71,585.70,507.96cm -1 .
step six: (E) Preparation of (E) -4- (1H-indol-5-yl) -2-methylbut-3-en-2-ol (5-5):
to a two-necked round bottom flask, under nitrogen protection, magnetons and condenser tubes, 5-bromo-1H-indole (78mg, 0.4mmol, 1.0eq.), bis (tri-tert-butylphosphine) palladium (0) (16.4mg, 0.032mmol, 0.08eq.), toluene (3 mL, 10min bubbling with nitrogen before addition), et3N (82 μ L,0.6mmol, 1.5eq.), 1-dimethylallyl alcohol (184 μ L,1.8mmol, 4.5eq.); then the reaction flask is sealed and placed in an oil bath at 100 ℃; after 30 minutes of reaction, the reaction mixture was cooled to room temperature and 1mL of saturated NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; the crude reaction product was then filtered through celite and washed with ethyl acetate (30 mL); the filtrate was diluted with ethyl acetate (50 mL) and extracted with water (2X 10 mL) and brine (10 mL); the combined organic phases were treated with anhydrous Na 2 SO 4 Drying, filtering the organic phase and concentrating in vacuo at 30 ℃ to provide a crude product; after purification by flash column chromatography (PE: EA =8, 1 to 2), the target compound was obtained (73.3mg, 93% yield);
(E) -4- (1H-indol-5-yl) -2-methylbut-3-en-2-ol structural data characterisation:
1 H NMR(400MHz,CDCl 3 )δ8.35(s,1H),7.64(s,1H),7.31(d,J＝1.5Hz,2H),7.20–7.12(m,1H),6.70(d,J＝16.1Hz,1H),6.57–6.47(m,1H),6.33(d,J＝16.1Hz,1H),1.46(s,6H)；
13 C NMR(100MHz,CDCl 3 )δ135.49,134.71,128.87,128.14,127.50,124.80,120.46,119.21,111.27,102.72,71.28,31.02,29.97；
IR(KBr):3517.70,3362.91,3271.93,2953.63,1335.48,1115.94,969.39,800.64,732.30,471.72cm -1 .
step seven: (E) Preparation of-2-methyl-4- (thiophen-3-yl) but-3-en-2-ol (5-6):
under nitrogen protection, to a two-necked round bottom flask, magnetons and a condenser were added, 3-bromothiophene (65mg, 0.4mmol, 1.0eq.), bis (tri-tert-butylphosphine) palladium (0) (16.4mg, 0.032mmol, 0.08eq.), toluene (3 mL, 10min with nitrogen bubbling before addition), et3N (82. Mu.L, 0.6mmol, 1.5eq.), 1-dimethylallyl alcohol (184. Mu.L, 1.8mmol, 4.5eq.); then the reaction bottle is sealed and placed in an oil bath at 100 ℃; after 30 minutes of reaction, the reaction mixture was cooled to room temperature and 1mL of saturated NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; the crude reaction product was then filtered through celite and washed with ethyl acetate (30 mL); the filtrate was diluted with ethyl acetate (50 mL) and extracted with water (2X 10 mL) and brine (10 mL); the combined organic phases were treated with anhydrous Na 2 SO 4 Drying, filtering the organic phase and concentrating in vacuo at 30 ℃ to provide a crude product; after purification by flash column chromatography (PE: EA =8, 1 to 2).
(E) -2-methyl-4- (thiophen-3-yl) but-3-en-2-ol structural data characterisation:
1 H NMR(400MHz,CDCl 3 )δ7.27(dd,J＝5.1,2.9Hz,1H),7.21(dd,J＝5.1,1.2Hz,1H),7.14(dd,J＝3.0,1.2Hz,1H),6.60(d,J＝16.1Hz,1H),6.22(d,J＝16.0Hz,1H),1.41(s,6H)；
13 C NMR(100MHz,CDCl 3 )δ139.49,137.40,126.09,124.95,121.94,120.72,70.98,29.87；
IR(KBr):3855.32,3512.80,3288.92,3194.79,3047.73,2837.25,2638.89,2348.34,1402.00,1141.69,982.26,832.22,724.20,656.28,521.57cm -1 .
as a further embodiment of the present invention, the saturated solution of sodium bicarbonate may be replaced by potassium bicarbonate, sodium carbonate, potassium carbonate, calcium carbonate, sodium monohydrogen phosphate, sodium dihydrogen phosphate, potassium monohydrogen phosphate, potassium dihydrogen phosphate, potassium phosphate, sodium phosphate, or calcium phosphate.
As a further embodiment of the present invention, the tri-tert-butylphosphine may be replaced by triphenylphosphine, trimethylphosphine, tris (o-methylphenyl) phosphorus, tricyclohexylphosphine borofluoride, tri-N-butylphosphine, 4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene, bis (2-diphenylphosphinophenyl) ether, tris (2-furyl) phosphine, tri-tert-butylphosphine tetrafluoroborate, 1, 2-bis (diphenylphosphine) ethane, 1, 3-bis (diphenylphosphine) propane, 1, 4-bis (diphenylphosphine) butane, 2- (di-tert-butylphosphine) biphenyl, 2- (dicyclohexylphosphino) biphenyl, 2-dicyclohexylphosphino-2 ',6' -dimethoxybiphenyl, 2-dicyclohexylphosphino-2 ' - (N, N-dimethylamine) -biphenyl, 2-dicyclohexylphosphine-2 ',4',6' -triisopropylbiphenyl, N-butylbis (1-adamantyl) phosphine, 1' -bis (diisopropylphosphine) ferrocene, R- (+) -1,1' -binaphthyl-2, 2' -bisdiphenylphosphine, 1' -bi-2-naphthol, 5' -bis (diphenylphosphoryl) -4,4' -di-1, 3-biphenyl, bisdiphenylphosphorylbiphenyl, bis (2-diphenylphosphinyl) ether, 1-bis (di-tert-butylphosphino) -ferrocene, 2-di-tert-butylphosphino-2 ',4',6' -triisopropylbiphenyl, palladium tetrakistriphenylphosphine chloride, bis (tri-tert-butylphosphine) palladium, [1,1' -bis (di-tert-butylphosphine) ferrocene ] palladium (II) dichloride or without addition of ligands.
As a further aspect of the present invention, triethylamine may be replaced with tri-N-propylamine, N-diisopropylethylamine, N-diethylaniline, tri-N-octylamine, N-cyclohexylmethylamine, pyridine, 4-dimethylaminopyridine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, 1, 4-diazabicyclo [2.2.2] octane, tetrabutylammonium chloride, tetrabutylammonium bromide, triethylenediamine, N-methyldicyclohexylamine, tetrabutylammonium hydroxide, potassium acetate, sodium bicarbonate, potassium bicarbonate, ammonium bicarbonate, sodium carbonate, potassium carbonate, ammonium carbonate, calcium carbonate, cesium carbonate, sodium monohydrogen phosphate, sodium dihydrogen phosphate, potassium monohydrogen phosphate, potassium dihydrogen phosphate, potassium phosphate, sodium phosphate, calcium phosphate, or no base addition.
In a further embodiment of the present invention, the toluene may be substituted for tetrahydrofuran, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone, benzene, xylene, 1, 4-dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, 1, 2-dichloroethane, polyethylene glycol, acetonitrile, chlorobenzene, dimethylsulfoxide, or no solvent is added.
As a further scheme of the invention, the reaction temperature in the synthesis process is between 40 ℃ and 145 ℃.
As a further embodiment of the present invention, the bromination substrate is:
Figure BDA0003880053050000141
or other similar brominated substrates.
As a further embodiment of the present invention, the olefinic compound is:
Figure BDA0003880053050000151
or other olefinic compounds.

Claims (8)

1. A process for the synthesis of compounds containing a dimethyl enol group, characterized in that: the synthetic method of the compound containing the dimethyl enol group comprises the following steps:
the method comprises the following steps: preparation of E-suberenol (5)
Figure RE-FDA0003948827160000011
Under the protection of nitrogen, adding magnetons and a condenser tube into a double-neck round-bottom flask, and adding a brominated substrate 1, bis (tri-tert-butylphosphine) palladium (0), toluene, triethylamine and an olefin compound 2; then the reaction bottle is sealed and put in an oil bath at 90 ℃; after completion of the reaction (monitored by TLC, about 12 min), the reaction mixture was cooled to room temperature and NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; the insoluble solid was removed by transferring through a short column of silica gel with ethyl acetate and washing with ethyl acetate; diluting the filtrate with ethyl acetate, extracting with water for 3 times, and extracting with saturated sodium chloride for 1 time; the combined organic layers were washed with anhydrous Na 2 SO 4 Drying, filtering the organic phase, and concentrating to obtain a crude product; wetAfter column chromatography purification of a sample on the method, a compound E-suberenol is obtained;
step two: (E) Preparation of 2-methyl-4- (2, 4, 6-trimethoxyphenyl) but-3-en-2-ol (5-1):
adding magnetons and condenser, 2-bromo-1, 3, 5-trimethoxybenzene, bis (tri-tert-butylphosphine) palladium (0), and toluene to a two-necked round-bottomed flask under nitrogen protection to fill the two-necked round-bottomed flask with Et 3 N, olefin compound 2 (1, 1-dimethylallyl alcohol); then the reaction bottle is sealed and placed in an oil bath at 100 ℃; after completion of the reaction (monitored by TLC, about 1 hour), the reaction mixture was cooled to room temperature and 1mL of saturated NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; then filtering the reaction crude product through diatomite, and washing the reaction crude product with ethyl acetate; the filtrate was diluted with ethyl acetate and extracted with water and brine; the combined organic phases were treated with anhydrous Na 2 SO 4 Drying, filtering the organic phase and concentrating in vacuo at 30 ℃ to provide a crude product; purifying by flash column chromatography to obtain target compound;
step three: (E) Preparation of (E) -4- (4- (ethoxymethoxy) phenyl) -2-methylbutyl-3-en-2-ol (5-2):
under the protection of nitrogen, adding magnetons, a condenser, 1-bromo-4- (ethoxymethoxymethyl) benzene, bis (tri-tert-butylphosphine) palladium (0), toluene and Et into a double-neck round-bottom flask 3 N, olefin compound 2 (1, 1-dimethylallyl alcohol); then the reaction bottle is sealed and placed in an oil bath at 100 ℃; after completion of the reaction (monitored by TLC, about 30 min), the reaction mixture was cooled to room temperature and 1mL of saturated NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; then filtering the reaction crude product through diatomite and washing the reaction crude product with ethyl acetate; the filtrate was diluted with ethyl acetate and extracted with water and brine; the combined organic phases were treated with anhydrous Na 2 SO 4 Drying, filtering the organic phase and concentrating in vacuo at 30 ℃ to provide a crude product; purifying by flash column chromatography to obtain target compound;
step four: (E) Preparation of (E) -1- (2-hydroxy-5- (3-hydroxy-3-methylbut-1-en-1-yl) -4-methoxyphenyl) ethan-1-one (5-3):
in the presence of nitrogen gasUnder the protection, a two-neck round-bottom flask is added with magnetons and a condenser, 1- (5-bromo-2-hydroxy-4-methoxymethyl benzene) ethane-1-one, bis (tri-tert-butylphosphine) palladium (0), toluene and Et 3 N, olefin compound 2 (1, 1-dimethylallyl alcohol); then the reaction flask is sealed and placed in an oil bath at 100 ℃; after completion of the reaction (monitored by TLC, about 1 hour), the reaction mixture was cooled to room temperature and 1mL of saturated NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; then filtering the reaction crude product through diatomite and washing the reaction crude product with ethyl acetate; the filtrate was diluted with ethyl acetate and extracted with water and brine; the combined organic phases were treated with anhydrous Na 2 SO 4 Drying, filtering the organic phase and concentrating in vacuo at 30 ℃ to provide a crude product; purifying by flash column chromatography to obtain target compound;
step five: (E) Preparation of (E) -4- (benzofuran-5-yl) -2-methylbut-3-en-2-ol (5-4):
under the protection of nitrogen, adding magnetons, a condenser, 5-bromobenzofuran, bis (tri-tert-butylphosphine) palladium (0), toluene and Et into a double-neck round-bottom flask 3 N, olefin compound 2 (1, 1-dimethylallyl alcohol); then the reaction bottle is sealed and placed in an oil bath at 100 ℃; after 30 minutes of reaction, the reaction mixture was cooled to room temperature and 1mL of saturated NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; then filtering the reaction crude product through diatomite and washing the reaction crude product with ethyl acetate; the filtrate was diluted with ethyl acetate and extracted with water and brine; the combined organic phases were treated with anhydrous Na 2 SO 4 Drying, filtering the organic phase and concentrating in vacuo at 30 ℃ to provide a crude product; purifying by flash column chromatography to obtain target compound;
step six: (E) Preparation of (E) -4- (1H-indol-5-yl) -2-methylbut-3-en-2-ol (5-5):
adding magnetons and a condenser tube, 5-bromo-1H-indole, bis (tri-tert-butylphosphine) palladium (0), toluene, et3N (82. Mu.L, 0.6mmol,1.5 eq.), and an olefin compound 2 (1, 1-dimethylallyl alcohol) into a double-neck round-bottom flask under the protection of nitrogen; then the reaction bottle is sealed and placed in an oil bath at 100 ℃; after 30 minutes of reaction, the reaction mixture was cooled to room temperature and 1mL of saturated NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; then filtering the reaction crude product through diatomite, and washing the reaction crude product with ethyl acetate; the filtrate was diluted with ethyl acetate and extracted with water and brine; the combined organic phases were treated with anhydrous Na 2 SO 4 Drying, filtering the organic phase and concentrating in vacuo at 30 ℃ to provide a crude product; purifying by flash column chromatography to obtain target compound;
step seven: (E) Preparation of-2-methyl-4- (thiophen-3-yl) but-3-en-2-ol (5-6):
under the protection of nitrogen, adding magnetons and a condenser, 3-bromothiophene, bis (tri-tert-butylphosphine) palladium (0), toluene and Et into a double-neck round-bottom flask 3 N, olefin compound 2 (1, 1-dimethylallyl alcohol); then the reaction bottle is sealed and placed in an oil bath at 100 ℃; after 30 minutes of reaction, the reaction mixture was cooled to room temperature and 1mL of saturated NaHCO was added 3 Aqueous solution, then stirred for 5 minutes; then filtering the reaction crude product through diatomite and washing the reaction crude product with ethyl acetate; the filtrate was diluted with ethyl acetate and extracted with water and brine; the combined organic phases were treated with anhydrous Na 2 SO 4 Drying, filtering the organic phase and concentrating in vacuo at 30 ℃ to provide a crude product; after purification by flash column chromatography, the target compound was obtained.
2. The process for the synthesis of compounds containing a dimethyl-enol group according to claim 1, characterized in that: the saturated solution of sodium bicarbonate can be replaced by potassium bicarbonate, sodium carbonate, potassium carbonate, calcium carbonate, sodium monohydrogen phosphate, sodium dihydrogen phosphate, potassium monohydrogen phosphate, potassium dihydrogen phosphate, potassium phosphate, sodium phosphate and calcium phosphate.
3. The process for the synthesis of compounds containing a dimethylethenol group according to claim 1, characterized in that: the tri-tert-butylphosphine may be replaced by triphenylphosphine, trimethylphosphine, tris (o-methylphenyl) phosphorus, tricyclohexylphosphine fluoroborate, tri-N-butylphosphine, 4, 5-bis (diphenylphosphine) -9, 9-dimethylxanthene, bis (2-diphenylphosphinophenyl) ether, tris (2-furyl) phosphine, tri-tert-butylphosphine tetrafluoroborate, 1, 2-bis (diphenylphosphine) ethane, 1, 3-bis (diphenylphosphine) propane, 1, 4-bis (diphenylphosphine) butane, 2- (di-tert-butylphosphine) biphenyl, 2- (dicyclohexylphosphino) biphenyl, 2-dicyclohexylphosphino-2 ',6' -dimethoxybiphenyl, 2-dicyclohexylphosphino-2 ' - (N, N-dimethylamine) -biphenyl, 2-dicyclohexylphosphine-2 ',4',6' -triisopropylbiphenyl, N-butylbis (1-adamantyl) phosphine, 1' -bis (diisopropylphosphine) ferrocene, R- (+) -1,1' -binaphthyl-2, 2' -bisdiphenylphosphine, 1' -bi-2-naphthol, 5' -bis (diphenylphosphoryl) -4,4' -di-1, 3-biphenyl, bisdiphenylphosphorylbiphenyl, bis (2-diphenylphosphinyl) ether, 1-bis (di-tert-butylphosphino) -ferrocene, 2-di-tert-butylphosphino-2 ',4',6' -triisopropylbiphenyl, palladium tetrakistriphenylphosphine chloride, bis (tri-tert-butylphosphino) palladium, [1,1' -bis (di-tert-butylphosphino) ferrocene ] palladium (II) dichloride or no ligand added.
4. The process for the synthesis of compounds containing a dimethylethenol group according to claim 1, characterized in that: the triethylamine can be replaced by tri-N-propylamine, N-diisopropylethylamine, N-diethylaniline, tri-N-octylamine, N, N-cyclohexylmethylamine, pyridine, 4-dimethylaminopyridine, 1, 8-diazabicyclo [5.4.0] undec-7-ene, 1, 4-diazabicyclo [2.2.2] octane, tetrabutylammonium chloride, tetrabutylammonium bromide, triethylenediamine, N-methyldicyclohexylamine, tetrabutylammonium hydroxide, potassium acetate, sodium hydrogen carbonate, potassium hydrogen carbonate, ammonium hydrogen carbonate, sodium carbonate, potassium carbonate, ammonium carbonate, calcium carbonate, cesium carbonate, sodium monohydrogen phosphate, sodium dihydrogen phosphate, potassium monohydrogen phosphate, potassium dihydrogen phosphate, potassium phosphate, sodium phosphate, calcium phosphate or no base is added.
5. The process for the synthesis of compounds containing a dimethylethenol group according to claim 1, characterized in that: the toluene can replace tetrahydrofuran, N-dimethylformamide, N-dimethylacetamide, N-methylpyrrolidone, benzene, xylene, 1, 4-dioxane, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, 1, 2-dichloroethane, polyethylene glycol, acetonitrile, chlorobenzene, dimethyl sulfoxide or no solvent is added.
6. The process for the synthesis of compounds containing a dimethylethenol group according to claim 1, characterized in that: the reaction temperature in the synthesis process is between 40 and 145 ℃.
7. The process for the synthesis of compounds containing a dimethylethenol group according to claim 1, characterized in that: the brominated substrate is:
Figure RE-FDA0003948827160000041
or other similar brominated substrates.
8. The process for the synthesis of compounds containing a dimethyl-enol group according to claim 1, characterized in that: the olefin compound is:
Figure RE-FDA0003948827160000042
or other olefinic compounds.
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