CN116969820A - Method for realizing visible light-induced intramolecular alkynyl migration of 1, 4-eneyne compound and realizing unactivated olefin difunctional - Google Patents
Method for realizing visible light-induced intramolecular alkynyl migration of 1, 4-eneyne compound and realizing unactivated olefin difunctional Download PDFInfo
- Publication number
- CN116969820A CN116969820A CN202311015130.8A CN202311015130A CN116969820A CN 116969820 A CN116969820 A CN 116969820A CN 202311015130 A CN202311015130 A CN 202311015130A CN 116969820 A CN116969820 A CN 116969820A
- Authority
- CN
- China
- Prior art keywords
- migration
- eneyne
- visible light
- intramolecular
- alkyne
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000013508 migration Methods 0.000 title claims abstract description 52
- 230000005012 migration Effects 0.000 title claims abstract description 49
- 150000001875 compounds Chemical class 0.000 title claims abstract description 44
- 150000001336 alkenes Chemical class 0.000 title claims abstract description 36
- 238000000034 method Methods 0.000 title claims abstract description 32
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 title claims description 28
- 125000000304 alkynyl group Chemical group 0.000 title claims description 25
- 238000006243 chemical reaction Methods 0.000 claims abstract description 35
- 239000002904 solvent Substances 0.000 claims abstract description 21
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 21
- 239000012299 nitrogen atmosphere Substances 0.000 claims abstract description 8
- 239000011941 photocatalyst Substances 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- 239000001257 hydrogen Substances 0.000 claims abstract description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
- 239000003513 alkali Substances 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- 150000001345 alkine derivatives Chemical class 0.000 claims description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 14
- 238000010898 silica gel chromatography Methods 0.000 claims description 9
- 238000002156 mixing Methods 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 239000003208 petroleum Substances 0.000 claims description 7
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 7
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 7
- 239000011736 potassium bicarbonate Substances 0.000 claims description 7
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical group [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 7
- 238000000746 purification Methods 0.000 claims description 7
- 238000007789 sealing Methods 0.000 claims description 7
- 238000000926 separation method Methods 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- 125000000524 functional group Chemical group 0.000 claims description 5
- 239000002585 base Substances 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 3
- 239000007789 gas Substances 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000002390 rotary evaporation Methods 0.000 claims description 2
- 230000009977 dual effect Effects 0.000 claims 2
- 239000003054 catalyst Substances 0.000 abstract description 5
- 238000007306 functionalization reaction Methods 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 3
- 238000011160 research Methods 0.000 abstract description 3
- 125000002355 alkine group Chemical group 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 230000006698 induction Effects 0.000 abstract 1
- 150000002611 lead compounds Chemical class 0.000 abstract 1
- 238000012216 screening Methods 0.000 abstract 1
- 238000012360 testing method Methods 0.000 abstract 1
- -1 alkyl radical Chemical group 0.000 description 21
- 229930182555 Penicillin Natural products 0.000 description 20
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 20
- 229940049954 penicillin Drugs 0.000 description 20
- 150000003254 radicals Chemical class 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 6
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 6
- 238000001035 drying Methods 0.000 description 5
- 239000011259 mixed solution Substances 0.000 description 5
- 238000005086 pumping Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000012544 monitoring process Methods 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000005905 alkynylation reaction Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- HVAPLSNCVYXFDQ-UHFFFAOYSA-N 3,3-dimethyl-1-(trifluoromethyl)-1$l^{3},2-benziodoxole Chemical compound C1=CC=C2C(C)(C)OI(C(F)(F)F)C2=C1 HVAPLSNCVYXFDQ-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 description 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 1
- 150000007824 aliphatic compounds Chemical class 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 230000001088 anti-asthma Effects 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 230000000941 anti-staphylcoccal effect Effects 0.000 description 1
- 239000000924 antiasthmatic agent Substances 0.000 description 1
- 229940125683 antiemetic agent Drugs 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 229940033495 antimalarials Drugs 0.000 description 1
- 239000003972 antineoplastic antibiotic Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- RHDGNLCLDBVESU-UHFFFAOYSA-N but-3-en-4-olide Chemical compound O=C1CC=CO1 RHDGNLCLDBVESU-UHFFFAOYSA-N 0.000 description 1
- HXCHCVDVKSCDHU-LULTVBGHSA-N calicheamicin Chemical compound C1[C@H](OC)[C@@H](NCC)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@](C/3=C/CSSSC)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HXCHCVDVKSCDHU-LULTVBGHSA-N 0.000 description 1
- 229930195731 calicheamicin Natural products 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000012822 chemical development Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 150000002212 flavone derivatives Chemical class 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- YALSXYCXTKPOFY-UHFFFAOYSA-N pent-1-en-4-yn-3-ol Chemical compound C=CC(O)C#C YALSXYCXTKPOFY-UHFFFAOYSA-N 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000006552 photochemical reaction Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 229930185107 quinolinone Natural products 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 239000003451 thiazide diuretic agent Substances 0.000 description 1
- 238000006276 transfer reaction Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 238000006692 trifluoromethylation reaction Methods 0.000 description 1
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/008—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reaction with tri- or tetrahalomethyl compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/79—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/81—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The method for transferring alkyne groups in a molecule of a 1, 4-eneyne compound by visible light induction and realizing unactivated alkene difunctional group relates to a method for transferring alkene alkyne groups, and aims to solve the technical problems of expensive catalyst, harsh reaction conditions and poor regioselectivity of the existing direct selective functionalization method. The method comprises the following steps: adding 1, 4-eneyne compound, trifluoromethyl source, photocatalyst, alkali and solvent into transparent reactor, reacting under nitrogen atmosphere with blue LED light, and purifying to obtain eneyne intramolecularAlkynyl groups migrate and effect the difunctional product of the unactivated alkene; the structural formula of the product is as follows:wherein R is hydrogen or alkyl. The method realizes difunctional olefine through a migration strategy in molecules, constructs an alkynone structure and introduces trifluoromethyl groups, can be used for screening a drug lead compound or testing bioactivity, and can also be used in the field of organic methodology mechanism research.
Description
Technical Field
The invention relates to a preparation method for alkene alkynyl migration, and belongs to the field of organic synthesis.
Background
Free radical mediated bi-functionalization of olefins has provided an effective tool for rational regulation of olefins over the past few years, and has attracted considerable attention. Mechanically, the free radical adds to the double bond in the olefin molecule to form a secondary or tertiary alkyl radical which can be intercepted by an external radical trapping agent to yield a difunctional product; or further cyclizes with unsaturated bonds in the molecule to generate cyclized products; rearrangement of specific groups (e.g., aryl, alkynyl) can also occur, resulting in products of different group migration. Alkynyl is a very important functional group in organic chemistry, and the alkyne compound is widely applied to the multi-disciplinary intersection fields of organic chemistry, medicinal chemistry, chemical biology and the like, and is a high-efficiency antitumor antibiotic Calicheamicin compared with a typical medicament. It follows that it is particularly important to develop an efficient alkynylation process. Meanwhile, fluorine-containing compounds are also increasingly being widely used. In recent years, intramolecular functional group transfer reactions induced by free radicals have received widespread attention.
Thus, it is of particular importance to develop a new method for the realization of alkynylation of olefins under mild conditions, particularly with visible light induced trifluoromethylation of olefins, while intramolecular alkyne transport. Trifluoromethyl compounds are an important class of compounds, of which about 50 have been tested for biological activity. Trifluoromethyl groups are contained in both the anesthetic aliphatic compounds and in phenothiazine tranquilizers and antiemetics, benzothiadiazine diuretics, and in some compounds which have not been evaluated clinically, such as antihistamines, antiasthmatics, antimalarials, and anti-Staphylococcus aureus. Alkynones are very attractive precursors for the synthesis of heterocyclic compounds, such as pyrrole, furan, furanone, pyrazole, isoxazole, pyrimidine, quinolinone, flavone, etc., which can be used as templates in the synthesis process. Meanwhile, the compounds are useful synthetic intermediates for preparing furan, 1, 4-dicarbonyl compounds, adjacent pyrrole and bicyclo compounds, are key skeletons or intermediates of a plurality of medicaments, spices or pesticides, and have wide application scenes.
In recent years, studies on trifluoromethyl-promoted intramolecular functional group migration have been greatly advanced, mainly including intramolecular 1, 4-migration, 1, 5-migration, 1, 2-migration and the like, and in general, studies on 1, 2-alkynyl migration have been relatively few. Although many migration types have been developed, the current research still has many limitations, requiring further improvements and developments: (1) Most reactions still use transition metal catalysis, experimental conditions need to be further improved, a milder reaction system is developed, and the requirements of green chemical development are met; (2) Most of the free radical sources used at present are expensive, such as trifluoromethyl source Umemoto's reagent, togni's reagent, langloi's reagent and the like, so that relatively cheap and easily available free radical sources should be developed to reduce the cost of the reaction.
Disclosure of Invention
The invention aims to solve the technical problems of expensive catalyst, harsh reaction conditions and poor regioselectivity of the existing direct selective functionalization method, and provides a method for realizing the double-functional functionalization of unactivated olefin by the intramolecular alkynyl migration of a 1, 4-eneyne compound induced by visible light.
The method for realizing the visible light induced migration of the alkynyl in the molecule of the 1, 4-eneyne compound and the difunctional of the unactivated olefin comprises the following steps:
1. at room temperature, adding a 1, 4-eneyne compound, a trifluoromethyl source, a photocatalyst and alkali into a transparent reactor, and sealing; then using nitrogen to replace the gas in the reactor to form nitrogen atmosphere, then injecting solvent, and uniformly mixing; the reactor is irradiated with blue LEDs to react;
2. after the reaction is finished, removing the solvent by rotary evaporation, and separating and purifying by a prefabricated silica gel column chromatography to obtain an alkyne product with the alkyne in the alkene alkyne molecule migrating and realizing unactivated alkene difunctional;
wherein the structural formula of the 1, 4-eneyne compound in the first step is as follows:wherein R is hydrogen or alkyl;
the structural formula of the trifluoromethyl source in the first step is as follows:
the photocatalyst in the first step is fac-Ir (ppy) 3 The structural formula is as follows:
the structural formula of the product for realizing the difunctional group of the unactivated olefin by the migration of the alkynyl in the eneyne molecule in the second step is as follows:wherein R is hydrogen or alkyl.
Still further, the base in step one is potassium bicarbonate.
Further, the solvent in the first step is methanol or acetonitrile.
Further, in the first step, the molar ratio of the 1, 4-eneyne compound to the trifluoromethyl source is 1 (1 to 3).
Further, in the first step, the molar ratio of the 1, 4-eneyne compound to the base is 1 (1-2).
Still further, in the first step, the ratio of the amount of the substance of the 1, 4-eneyne compound to the volume of the solvent is 1mmol: (1-10) mL.
Further, in the first step, the molar ratio of the 1, 4-eneyne compound to the photocatalyst is 1 (1-4).
Further, the LEDs in the first step are 5-30W, and the irradiation reaction time is 1-4 days.
Further, the solvent used in the separation and purification of the silica gel column chromatography in the first step is a mixed solvent of petroleum ether and ethyl acetate according to the volume ratio of (10-1): 1.
The synthetic process of the preparation method of the invention is represented by the following reaction formula:
the invention adopts a simple and efficient one-step method for 1, 4-eneyne intramolecular alkyne migration compound, wherein fac-Ir (ppy) is adopted 3 As a catalyst, a catalyst having a specific molecular weight,the invention has the advantages that the visible light-promoted and initiated photochemical reaction is carried out on the alkinyl compound and the trifluoromethyl reagent, and in the reaction system, the trifluoromethyl has excellent free radical reactivity, electrophilicity and nucleophilicity, so that the reaction is smoothly carried out, and the alkinyl hydrocarbon has selective migration. The visible light of natural abundance as driving force has the advantages of reproducibility, green and no pollution, and the preparation conditions are mild, the catalyst is safe, the operation is simple, and the energy consumption is low.
The method realizes difunctional olefin through a migration strategy in the molecule, constructs an alkynone structure and introduces a trifluoromethyl group, thus greatly improving the atom economy of the reaction and having important synthesis value and research significance. The 1, 4-eneyne intramolecular alkynyl migration trifluoromethyl compound prepared by the invention has good biomedical potential and can further improve the application value.
Drawings
FIG. 1 shows the intramolecular alkyne migration of 1, 4-eneyne in trifluoromethyl compounds obtained in example 1 1 H NMR spectrum.
FIG. 2 shows the intramolecular alkyne migration of 1, 4-eneyne in trifluoromethyl compounds obtained in example 1 13 C NMR spectrum.
Detailed Description
The following examples are used to demonstrate the benefits of the invention:
example 1: the method for the visible light induced intramolecular alkynyl migration of the 1, 4-eneyne compound and the realization of the dual-functional group of the unactivated olefin in the embodiment comprises the following steps:
1. 37mg (0.2 mmol) of 2, 3-dimethyl-5-phenylpent-1-en-4-yn-3-ol, 86.9mg (0.2 mmol) of S-trifluoromethylthiane triflate, 1.31mg (0.002 mmol) of fac-Ir (ppy) are reacted at room temperature 3 40mg (0.4 mmol) of potassium bicarbonate was added to a 10mL penicillin bottle, and the bottle was sealed with a rubber plug and a sealing film; then connecting a penicillin bottle with an air pump by using a needle, pumping out air in the penicillin bottle, backfilling with nitrogen, repeating for three times, forming a nitrogen atmosphere in the penicillin bottle, injecting 1mL of methanol as a solvent, and uniformly mixing; the reactor was inverted at room temperature using 30W blue LEDs lamp illuminationMonitoring the reaction progress by TLC, and completing the reaction after 1 day;
2. after the reaction is finished, concentrating and spin-drying by a rotary evaporator to remove the solvent, and then taking a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 5:1 as a developing agent to carry out silica gel column chromatography purification and separation to complete the visible light-induced 1, 4-eneyne compound intramolecular alkynyl migration and realize the dual-functional group of unactivated olefin, thereby obtaining the 1, 4-eneyne intramolecular alkynyl migration trifluoromethyl compound.
The reaction formula of this example is:
the product was a yellow liquid with a purity of 99% and a yield of 70%.
The product of this example 1 The H NMR spectrum is shown in figure 1, and the nuclear magnetic data are as follows: 1 H NMR(400MHz,Chloroform-d)δ7.47–7.39(m,2H),7.32(dd,J＝5.2,2.0Hz,3H),2.93-2.81(m,1H),2.68–2.36(m,4H),1.53(s,3H).
the product of this example 13 The C NMR spectrum is shown in figure 2, 13 C NMR(101MHz,Chloroform-d)δ205.58,131.51,128.55,128.32,125.61(q,J＝273.9Hz),122.43,88.14,85.87,44.36(d,J＝2.3Hz),41.25(q,J＝27.9Hz),26.20,25.60.
from the following components 1 H NMR spectrum 13 The C NMR spectrum showed that the structural formula of the product prepared in this example was:
in the embodiment, difunctional olefin is realized through an intramolecular migration strategy, an alkynone structure is constructed, and a trifluoromethyl group is introduced.
Example 2: the method for the visible light induced intramolecular alkynyl migration of the 1, 4-eneyne compound and the realization of the dual-functional group of the unactivated olefin in the embodiment comprises the following steps:
1. at room temperature, 40.1mg (0.2 m)mol) 2, 3-dimethyl-5- (p-toluene) pent-1-en-4-yn-3-ol, 86.9mg (0.2 mmol) S-trifluoromethylthiane triflate, 1.31mg (0.002 mmol) fac-Ir (ppy) 3 40mg (0.4 mmol) of potassium bicarbonate was added to a 10mL penicillin bottle, and the bottle was sealed with a rubber plug and a sealing film; then connecting a penicillin bottle with an air pump by using a needle, pumping out air in the penicillin bottle, backfilling with nitrogen, repeating for three times, forming a nitrogen atmosphere in the penicillin bottle, injecting 1mL of methanol as a solvent, and uniformly mixing; at room temperature, the reaction is carried out by using 30W blue LEDs to illuminate, TLC is used for monitoring the reaction progress, and the reaction is completed after 1 day;
2. after the reaction is finished, concentrating and spin-drying by a rotary evaporator to remove the solvent, and then taking a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 5:1 as a developing agent to carry out silica gel column chromatography purification and separation to complete the visible light-induced 1, 4-eneyne compound intramolecular alkynyl migration and realize the dual-functional group of unactivated olefin, thereby obtaining the 1, 4-eneyne intramolecular alkynyl migration trifluoromethyl compound.
The reaction formula of this example is:
the product of this example was a yellow liquid with a purity of 99% and a yield of 55%.
The nuclear magnetic data of the product of this example are:
1 H NMR(400MHz,CDCl 3 )δ7.35(d,J＝8.2Hz,2H),7.16(d,J＝7.9Hz,2H),2.89(dq,J＝15.1,10.7Hz,1H),2.64–2.42(m,4H),2.38(s,3H),1.55(s,3H)；
13 C NMR(151MHz,CDCl 3 )δ205.83,138.75,131.44,129.10,125.67(q,J＝279Hz),119.42,87.46,86.00,44.42,41.33(q,J＝27.9Hz),26.24,25.66,21.43。
from the following components 1 H NMR spectrum 13 The C NMR spectrum showed that the structure of the alkyne-migrating trifluoromethyl compound in the molecule of 1, 4-eneyne of this example is:
in the embodiment, difunctional olefin is realized through an intramolecular migration strategy, an alkynone structure is constructed, and a trifluoromethyl group is introduced.
Example 3: the method for the visible light induced intramolecular alkynyl migration of the 1, 4-eneyne compound and the realization of the dual-functional group of the unactivated olefin in the embodiment comprises the following steps:
1. 48.5mg (0.2 mmol) of 5- (4- (tert-butyl) phenyl) -2, 3-dimethylpent-1-en-4-yn-3-ol, 86.9mg (0.2 mmol) of S-trifluoromethylthioanthracene triflate, 1.31mg (0.002 mmol) of fac-Ir (ppy) at room temperature 3 40mg (0.4 mmol) of potassium bicarbonate was added to a 10mL penicillin bottle, and the bottle was sealed with a rubber plug and a sealing film; then connecting a penicillin bottle with an air pump by using a needle, pumping out air in the penicillin bottle, backfilling with nitrogen, repeating for three times, forming a nitrogen atmosphere in the penicillin bottle, injecting 1mL of methanol as a solvent, and uniformly mixing; at room temperature, the reaction is carried out by using 30W blue LEDs to illuminate, TLC is used for monitoring the reaction progress, and the reaction is completed after 1 day;
2. after the reaction is finished, concentrating and spin-drying by a rotary evaporator to remove the solvent, and then taking a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 3:1 as a developing agent to perform silica gel column chromatography purification and separation to complete the visible light-induced 1, 4-eneyne compound intramolecular alkynyl migration and realize the dual-functional group of unactivated olefin, thereby obtaining the 1, 4-eneyne intramolecular alkynyl migration trifluoromethyl compound.
The reaction formula of this example is:
the product of this example was a white solid with a purity of 99% and a yield of 40%.
The nuclear magnetic data of the product of this example are:
1 H NMR(400MHz,CDCl 3 )δ7.41(d,J＝8.8Hz,2H),7.38(d,J＝8.8Hz,2H).2.90(dq,J＝14.9,10.7Hz,1H),2.66–2.45(m,4H),1.56(s,3H),1.34(s,9H)；
13 C NMR(151MHz,CDCl 3 )δ205.83,151.92,131.28,125.63(q,J＝279Hz)125.33,119.44,87.50,85.95,44.38(d,J＝2.02Hz),41.33(q,J＝27.9Hz),34.75,31.11,26.23,25.67。
from the following components 1 H NMR spectrum 13 The structure of the product of this example was found to be:
in the embodiment, difunctional olefin is realized through an intramolecular migration strategy, an alkynone structure is constructed, and a trifluoromethyl group is introduced.
Example 4: the method for the visible light induced intramolecular alkynyl migration of the 1, 4-eneyne compound and the realization of the dual-functional group of the unactivated olefin in the embodiment comprises the following steps:
1. 45.7mg (0.2 mmol) of 2, 3-dimethyl-5- (4-propylphenyl) pent-1-en-4-yn-3-ol, 86.9mg (0.2 mmol) of S-trifluoromethylthiane triflate, 1.31mg (0.002 mmol) of fac-Ir (ppy) at room temperature 3 40mg (0.4 mmol) of potassium bicarbonate was added to a 10mL penicillin bottle, and the bottle was sealed with a rubber plug and a sealing film; then connecting a penicillin bottle with an air pump by using a needle, pumping out air in the penicillin bottle, backfilling with nitrogen, repeating for three times, forming a nitrogen atmosphere in the penicillin bottle, injecting 1mL of methanol as a solvent, and uniformly mixing; under the condition of room temperature, the reaction is carried out by using 5W blue LEDs to illuminate, TLC is used for monitoring the reaction progress, and the reaction is completed after 4 days;
2. after the reaction is finished, concentrating and spin-drying by a rotary evaporator to remove the solvent, and then taking a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 1:1 as a developing agent to carry out silica gel column chromatography purification and separation to complete the visible light-induced 1, 4-eneyne compound intramolecular alkynyl migration and realize the dual-functional group of unactivated olefin, thereby obtaining the 1, 4-eneyne intramolecular alkynyl migration trifluoromethyl compound.
The reaction formula of this example is:
the product of this example was a yellow liquid with a purity of 99% and a yield of 46%.
The nuclear magnetic data of the product of this example are: 1 H NMR(400MHz,CDCl 3 )δ7.37(d,J＝7.9Hz,2H),7.16(d,J＝7.8Hz,2H),2.87(dt,J＝14.8,10.7Hz,1H),2.71–2.40(m,6H),1.82–1.59(m,2H),1.55(s,3H),0.95(t,J＝7.3Hz,3H)；
13 C NMR(151MHz,CDCl 3 )δ205.89,143.52,131.43,128.69(q,J＝279Hz),128.51,119.62,87.47,86.03,42.20(q,J＝27.3Hz),37.92,29.69,26.27,25.69,24.33,13.69。
from the following components 1 H NMR spectrum 13 The structure of the product of this example was found to be:
in the embodiment, difunctional olefin is realized through an intramolecular migration strategy, an alkynone structure is constructed, and a trifluoromethyl group is introduced.
Example 5: the method for the visible light induced intramolecular alkynyl migration of the 1, 4-eneyne compound and the realization of the dual-functional group of the unactivated olefin in the embodiment comprises the following steps:
1. 45.7mg (0.2 mmol) of 2, 3-dimethyl-5- (3-methylphenyl) pent-1-en-4-yn-3-ol, 86.9mg (0.2 mmol) of S-trifluoromethylthiane triflate, 1.31mg (0.002 mmol) of fac-Ir (ppy) at room temperature 3 40mg (0.4 mmol) of potassium bicarbonate was added to a 10mL penicillin bottle, and the bottle was sealed with a rubber plug and a sealing film; then connecting a penicillin bottle with an air pump by using a needle, pumping out air in the penicillin bottle, backfilling with nitrogen, repeating for three times, forming a nitrogen atmosphere in the penicillin bottle, injecting 1mL of methanol as a solvent, and uniformly mixing; under the condition of room temperature, the reaction is carried out by using 5W blue LEDs to illuminate, TLC is used for monitoring the reaction progress, and the reaction is completed after 4 days;
2. after the reaction is finished, concentrating and spin-drying by a rotary evaporator to remove the solvent, and then taking a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 1:1 as a developing agent to carry out silica gel column chromatography purification and separation to complete the visible light-induced 1, 4-eneyne compound intramolecular alkynyl migration and realize the dual-functional group of unactivated olefin, thereby obtaining the 1, 4-eneyne intramolecular alkynyl migration trifluoromethyl compound.
The reaction formula of this example is:
the product of this example was a yellow liquid with a purity of 99% and a yield of 55%.
The nuclear magnetic data of the product of this example are: 1 H NMR(400MHz,Chloroform-d)δ7.33–7.19(m,3H),7.15(d,J＝7.2Hz,1H),2.87(dq,J＝15.1,10.8Hz,1H),2.49(s,4H),2.33(s,3H),1.53(s,3H)；
13 C NMR(101MHz,Chloroform-d)δ205.78,138.09,132.10,129.46,128.61,128.24,128.30(q,J＝279Hz),122.25,87.76,86.06,44.39,41.31(q,J＝27.9Hz),26.28,25.67,21.15.。
from the following components 1 H NMR spectrum 13 The structure of the product of this example was found to be:
in the embodiment, difunctional olefin is realized through an intramolecular migration strategy, an alkynone structure is constructed, and a trifluoromethyl group is introduced.
Claims (9)
1. A method for visible light induced intramolecular alkyne migration of a 1, 4-eneyne compound and realization of dual functional groups of an unactivated alkene, characterized in that the method comprises the following steps:
1. at room temperature, adding a 1, 4-eneyne compound, a trifluoromethyl source, a photocatalyst and alkali into a transparent reactor, and sealing; then using nitrogen to replace the gas in the reactor to form nitrogen atmosphere, then injecting solvent, and uniformly mixing; the reactor is irradiated with blue LEDs to react;
2. after the reaction is finished, removing the solvent by rotary evaporation, and separating and purifying by prefabricated silica gel column chromatography to complete visible light-induced 1, 4-eneyne compound intramolecular alkyne migration and realize unactivated olefin difunctional, so as to obtain an eneyne intramolecular alkyne migration and realize unactivated olefin difunctional product;
wherein the structural formula of the 1, 4-eneyne compound in the first step is as follows:wherein R is hydrogen or alkyl;
the structural formula of the trifluoromethyl source in the first step is as follows:
the photocatalyst in the first step is fac-Ir (ppy) 3 The structural formula is as follows:
the structural formula of the product for realizing the difunctional group of the unactivated olefin by the migration of the alkynyl in the eneyne molecule in the second step is as follows:wherein R is hydrogen or alkyl.
2. The method for visible light-induced intramolecular alkyne migration of a 1, 4-eneyne compound according to claim 1, wherein said base in step one is potassium bicarbonate.
3. The method for visible light-induced intramolecular alkyne migration of a 1, 4-eneyne compound according to claim 1 or 2, wherein said solvent in step one is methanol or acetonitrile.
4. The method for the visible light-induced intramolecular alkyne migration of a 1, 4-eneyne compound and the realization of the dual functional group of an unactivated olefin according to claim 1 or 2, wherein in the first step, the molar ratio of the 1, 4-eneyne compound to the trifluoromethyl source is 1 (1-3).
5. The method for the visible light-induced intramolecular alkyne migration of a 1, 4-eneyne compound according to claim 1 or 2, wherein in the step one, the molar ratio of the 1, 4-eneyne compound to the base is 1 (1-2).
6. The method for visible light-induced intramolecular alkyne migration of a 1, 4-eneyne compound according to claim 1 or 2, wherein the ratio of the amount of the substance of the 1, 4-eneyne compound to the volume of the solvent in step one is 1mmol: (1-10) mL.
7. The method for the visible light-induced intramolecular alkyne migration of a 1, 4-eneyne compound and the realization of the dual-functional group of an unactivated olefin according to claim 1 or 2, wherein in the first step, the molar ratio of the 1, 4-eneyne compound to the photocatalyst is 1 (1-4).
8. The method for the visible light-induced intramolecular alkyne migration of a 1, 4-eneyne compound according to claim 1 or 2, wherein said LEDs in step one are operated at 5 to 30 watts for a reaction time of 1 to 4 days.
9. The method for realizing the difunctional group of the unactivated olefin by the intramolecular alkynyl migration of the 1, 4-eneyne compound induced by the visible light according to claim 1 or 2, wherein the solvent used in the separation and purification of the silica gel column chromatography in the step one is a mixed solvent of petroleum ether and ethyl acetate according to the volume ratio of (10-1): 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311015130.8A CN116969820A (en) | 2023-08-14 | 2023-08-14 | Method for realizing visible light-induced intramolecular alkynyl migration of 1, 4-eneyne compound and realizing unactivated olefin difunctional |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311015130.8A CN116969820A (en) | 2023-08-14 | 2023-08-14 | Method for realizing visible light-induced intramolecular alkynyl migration of 1, 4-eneyne compound and realizing unactivated olefin difunctional |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116969820A true CN116969820A (en) | 2023-10-31 |
Family
ID=88473078
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311015130.8A Pending CN116969820A (en) | 2023-08-14 | 2023-08-14 | Method for realizing visible light-induced intramolecular alkynyl migration of 1, 4-eneyne compound and realizing unactivated olefin difunctional |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116969820A (en) |
-
2023
- 2023-08-14 CN CN202311015130.8A patent/CN116969820A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Nicolaou et al. | N-Phenylselenophthalimide (N-PSP) and N-phenylselenosuccinimide (N-PSS). Two versatile carriers of the phenylseleno group. Oxyselenation of olefins and a selenium-based macrolide synthesis | |
| US10513483B2 (en) | Method of preparing substituted bicyclo[1.1.1] pentanes | |
| Masamune et al. | Total synthesis of 6-deoxyerythronolide B | |
| CN111484452B (en) | Method for continuously preparing dihydro benzo [ j ] phenanthridine compound containing trifluoromethyl functional group by using microchannel reaction device | |
| CN114456121B (en) | Synthesis method of 1,2, 4-triazole derivative | |
| CN110305054B (en) | Preparation method of disubstituted styrene derivatives | |
| CN106349147A (en) | Synthetic method of pyrrole derivatives | |
| CN113912529B (en) | Method for synthesizing indole compounds by catalyzing N-aryl amide compounds and vinylene carbonate with ruthenium | |
| Wei et al. | Radical Carbosulfonylation of Propellane: Synthesis of Sulfonyl β-Keto-bicyclo [1, 1, 1] pentanes | |
| CN116969820A (en) | Method for realizing visible light-induced intramolecular alkynyl migration of 1, 4-eneyne compound and realizing unactivated olefin difunctional | |
| CN111072605B (en) | Preparation method of fluoroalkyl-substituted benzofuran derivative or indole derivative | |
| Corey et al. | Stereospecific synthesis of tetrasubstituted Z-enol silyl ethers by a three component coupling process | |
| CN116969819A (en) | Method for realizing visible light-induced intramolecular alkynyl migration of 1, 4-eneyne compound and realizing unactivated olefin difunctional | |
| CN114044751B (en) | Deuterated difluoromethylthio reagent, preparation method thereof and introduction of SCF (SCF) into drug molecules 2 Method for preparing D group | |
| CN113045479B (en) | Synthesis method of visible light-promoted 3-hydroxyisoindole-1-one compound | |
| CN110317170B (en) | Green synthesis method of 3-phenanthridinyl propyl formate compound | |
| CN110256315B (en) | Method for preparing conjugate containing thioether formyl thioester | |
| CN112279765B (en) | Preparation method of chiral alpha-fluoroketone compound | |
| CN113548965A (en) | Preparation method of 1, 4-eneyne compound | |
| CN111675650A (en) | Preparation method of aromatic vinyl bromide derivative | |
| Smitrovich et al. | Reactions of silylmethyl allylic silanes: Synthesis of tetrahydrofurans | |
| CN112608208B (en) | Synthesis method for preparing gamma-cyano olefin by decarboxylation at room temperature | |
| CN113277935B (en) | Far-end halogenated alkyl ketone using HX as halogen source and synthesis method thereof | |
| Wang et al. | An Efficient Enantioselective Synthesis of Florfenicol Based on Sharpless Asymmetric Dihydroxylation | |
| CN111620832B (en) | Multi-substituted oxazoline compound and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |