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CN-121990907-A - Method for synthesizing acyclic and non-terminal o-diol derivative based on propargyl alcohol ester

CN121990907ACN 121990907 ACN121990907 ACN 121990907ACN-121990907-A

Abstract

The invention discloses a method for synthesizing acyclic and non-terminal o-diol derivatives based on propargyl alcohol ester. The construction of the allyl skeleton substituted by the bimolecular exogenic nucleophilic group is realized by the coupling strategy of the propargyl alcohol ester and the exogenic nucleophilic reagent catalyzed by the transition metal (palladium). The strategy breaks the dilemma that the alkenyl products at the present stage are limited to the construction of cyclic molecules and terminal limited products, and provides a revolutionary synthesis scheme for transition metal catalyzed selective conversion of propargyl alcohol esters. The catalyst and ligand selected by the invention have wide sources, low cost and easy obtainment of substrates, excellent stereoselectivity and good functional group compatibility, can be suitable for structural transformation of bioactive molecules and intermediates, is a simple and efficient asymmetric catalytic strategy for synthesizing acyclic and non-terminal o-diol derivatives, and has good application prospect.

Inventors

  • CHEN LIANGAN
  • GAO YOUZHI
  • DAI MENGFU

Assignees

  • 南京师范大学

Dates

Publication Date
20260508
Application Date
20251209

Claims (10)

  1. 1. A process for synthesizing acyclic, non-terminal vicinal diol derivatives based on propargyl esters, characterized in that in a solvent, propargyl esters are used And carboxylic acid/phenol nucleophiles Or (b) As a reaction substrate, a catalytic system of transition metal palladium and an organic phosphine ligand is used for carrying out reaction in a base environment, and after the reaction is finished, the non-cyclic and non-terminal o-diol derivative is obtained Or (b) Wherein the molar ratio of propargyl alcohol ester to carboxylic acid to phenol to transition metal palladium to alkali is 1 (1-2): (0.01-0.2): (1-5), R 1 、R 2 and R 4 represent alkyl or aryl, and R 3 represents aryl.
  2. 2. The method for synthesizing acyclic, non-terminal o-diol derivatives based on propargyl alcohol esters according to claim 1, wherein the substituents of the alkyl groups are each independently selected from C1-C20 alkyl, C1-C20 haloalkyl, C1-C20 alkylcarbonyl, nitro, hydroxy, ester, alkenyl, ether, amide, silicon, mercapto, amino or cyano, wherein aryl represents heteroaryl wherein the benzene ring is optionally substituted with hydrogen, C1-C20 alkyl, C1-C20 halo-substituted alkyl, C1-C20 alkylcarbonyl, nitro, hydroxy, ester, alkenyl, ether, amide, silicon, mercapto, amino or cyano, or optionally substituted biphenyl, naphthyl, anthracene, and N, O, S-containing penta-tridecylic heteroaryl.
  3. 3. The method of synthesizing acyclic, non-terminal, vicinal diol derivatives based on propargyl esters according to claim 1, wherein the carboxylic acid/phenol nucleophile is selected from one or more of alkyl carboxylic acids/phenols, aryl carboxylic acids/phenols, amino carboxylic acids/phenols, alkoxy carboxylic acids/phenols, aryloxy carboxylic acids/phenols, aryl alkyl carboxylic acids/phenols.
  4. 4. The method of synthesizing acyclic, non-terminal vicinal diol derivatives based on propargyl esters according to claim 1, wherein the organophosphine ligand is a bidentate N ligand, a bidentate P ligand, a bidentate N-P ligand, a monodentate N ligand, a monodentate phosphine ligand, a tridentate N-P-N ligand, a tridentate N-S-P ligand, or a tridentate N ligand.
  5. 5. The method for synthesizing acyclic, non-terminal vicinal diol derivatives based on propargyl esters according to claim 4, wherein the organophosphine ligand is an oxazoline ligand, a diamine ligand, a monodentate phosphine ligand, a phosphoramidite ligand, a biphenyl bidentate phosphine ligand, a spiro bidentate phosphine ligand, a binaphthyl bidentate phosphine ligand, or a sulfenamide substituted phosphine ligand.
  6. 6. The method for synthesizing acyclic, non-terminal vicinal diol derivatives based on propargyl esters according to claim 5, wherein the organophosphine ligand is a biphenyl bidentate phosphine ligand, a chain bidentate phosphine ligand, a binaphthyl bidentate phosphine ligand, or a bidentate phosphine ligand of ferrocene skeleton.
  7. 7. The method of synthesizing acyclic, non-terminal vicinal diol derivatives based on propargyl alcohol esters according to claim 1, wherein the base is selected from one or more of sodium methoxide, sodium ethoxide, sodium tert-butoxide, potassium methoxide, potassium ethoxide, potassium tert-butoxide, sodium tert-amyl alcohol, potassium tert-amyl alcohol, sodium borohydride, sodium cyanoborohydride, lithium aluminum hydride, potassium carbonate, sodium carbonate, cesium carbonate, potassium phosphate, triethylamine, DBU (1, 8-diazabicyclo [5.4.0] undec-7-ene), triethylenediamine, TBD (1, 5, 7-triazido-bicyclo (4.4.0) dec-5-ene), tetramethylguanidine.
  8. 8. The method of synthesizing acyclic, non-terminal, o-diol derivatives based on propargyl esters according to claim 1, wherein the palladium is selected from palladium chloride, palladium bromide, palladium iodide, palladium acetate, palladium pivalate, bis (triphenylphosphine) palladium acetate, 1, 2-bis (diphenylphosphine) ethane palladium chloride, (1, 1' -bis (diphenylphosphine) ferrocene) palladium dichloride, palladium acetylacetonate, bis (hexafluoroacetylacetonate) palladium, bis (triphenylphosphine) palladium dichloride, tetrakis (triphenylphosphine) palladium, bis (tri-t-butylphosphine) palladium, bis (dibenzylideneacetone) palladium, chloro (crotyl) (tricyclohexylphosphine) palladium, tris (dibenzylideneacetone) dipalladium-chloroform adduct, (1, 5-cyclooctadiene) palladium dibromide, palladium trifluoroacetate, tetrakis (triphenylphosphine) palladium, allyldimeric chloride, (1-methallyl) palladium, bis (cyclopentadienyl) palladium chloride, bis (phenylphosphine) palladium, bis (phenylphosphine) 2-bis (phenylphosphine) palladium, bis (phenylphosphine) or acetonitrile.
  9. 9. The method of synthesizing acyclic, non-terminal, o-glycol derivatives based on propargyl alcohol esters according to claim 1, wherein the organic solvent is selected from one or more of methanol, ethanol, ethylene glycol, N-propanol, isopropanol, N-butanol, isobutanol, t-butanol, sec-butanol, t-amyl alcohol, 4-methyl-2-amyl alcohol, isoamyl alcohol, 2-amyl alcohol, diethyl ether, t-butyl methyl ether, N-butyl ether, isopropyl ether, diphenyl ether, dimethyl sulfide, cyclopentyl methyl ether, anisole, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, acetonitrile, benzonitrile, toluene, benzotrifluoride, acetone, dichloromethane, 1, 2-dichloroethane, dimethyl sulfoxide, N-dimethylformamide, N-dimethylacetamide, dimethyl sulfoxide, N-methylpyrrolidone, ethyl acetate, ethyl formate, propyl formate, 1, 4-dioxane, 1, 3-dioxolane, tetrahydrofuran, 2-methyltetrahydrofuran, or 1, 3-dimethyl-2-imidazolidinone.
  10. 10. The method for synthesizing acyclic, non-terminal vicinal diol derivatives based on propargyl alcohol esters according to claim 1, wherein the reaction is carried out under an atmosphere of inert gas at a temperature of 30 to 80 ℃ for a time of 8 to 36 hours.

Description

Method for synthesizing acyclic and non-terminal o-diol derivative based on propargyl alcohol ester Technical Field The invention belongs to the fields of catalytic synthesis technology and fine chemical synthesis, and relates to a method for synthesizing acyclic and non-terminal o-diol derivatives based on propargyl alcohol esters. Background The vicinal diol compound is an important fine chemical and has important application in the fields of cosmetics, medicines, pesticides, surfactants, polyesters, printing ink and the like. For a long time, there has been a great deal of attention from chemists how to achieve efficient, selective synthesis of vicinal diol derivatives. However, achieving synthesis of highly enantioselective vicinal diol derivatives based on catalytic asymmetry is a long standing scientific challenge, with great challenges. Currently, the preparation of dihydroxy compounds from olefins is a very common functional group conversion method in organic synthesis, such as potassium osmium, upjohn dihydroxylation, sharpless asymmetric dihydroxylation, and the like. However, most of the above methods are limited to the use of toxic and expensive osmium reagents, long reaction time, and the problem that the vicinal diols are easily oxidized to vicinal diketones under the reaction conditions and the yield is low. The transition metal catalyzed selective alkenylation of propargyl esters with nucleophilic substitution of carboxylic acids to build carbon-carbon/heterobonds is an effective strategy for synthesizing vicinal diol derivatives. However, since the carboxylic acid has a stable structure-COO -, not only nucleophilic substitution is difficult, but also the acidic H ion can quench nucleophilic reactive species, making it difficult for the carboxylic acid to react in a nucleophilic substitution pattern directly. The selective alkenylation of propargyl alcohol esters at present mainly adopts a ring-forming strategy to realize the synthesis of a single product. The main strategy is to couple propargyl esters with nucleophilic sites in the molecule with exogenous nucleophiles or to use conventional propargyl esters with binary nucleophiles for sequential nucleophilic substitution. Secondly, five-membered and six-membered ring structures with smaller angular tension structures are usually used in the strategies, so that the strategy has natural thermodynamic stability and is easy to realize highly selective construction. Although this ring-forming strategy largely circumvents the side reactions of conjugated dienylation, the generation of cyclic structures also limits the scope of application of this strategy. In order to avoid the steric (Z/E) isomerisation of the alkenylated product, most strategies are limited to the use of conjugated dienylated hindered propargyl esters and the construction of end-limited products is achieved. Therefore, developing a highly stereo, regio-and chemoselective construction strategy for the non-cyclic, polysubstituted vicinal diol derivatives by means of the alkenylation of propargyl alcohol esters with general applicability is of great practical and scientific interest. Disclosure of Invention In view of the problems of the prior art, the present invention provides a method for synthesizing acyclic, non-terminal vicinal diol derivatives based on propargyl esters. The method realizes the construction of the allyl skeleton substituted by the bimolecular exogenous nucleophilic group through a coupling strategy of transition metal (palladium) catalyzed propargyl alcohol ester and exogenous nucleophilic reagent. The strategy breaks the dilemma that the alkenyl products at the present stage are limited to the construction of cyclic molecules and terminal limited products, and provides a revolutionary synthesis scheme for transition metal catalyzed selective conversion of propargyl alcohol esters. In order to solve the problems in the prior art, the invention adopts the following technical scheme: Method for synthesizing acyclic, non-terminal o-diol derivative based on propargyl alcohol ester by using propargyl alcohol ester in solvent And a carboxylic acid/phenol nucleophile (Nu-H)Or (b)As a reaction substrate, a catalytic system of transition metal palladium and an organic phosphine ligand is used for carrying out reaction in a base environment, and after the reaction is finished, the non-cyclic and non-terminal o-diol derivative is obtainedOr (b)Wherein the molar ratio of propargyl alcohol ester to carboxylic acid to phenol to transition metal palladium to alkali is 1 (1-2): (0.01-0.2): (1-5), R 1、R2 and R 4 represent alkyl or aryl, and R 3 represents aryl. The reaction general formula is shown as follows Preferably, the substituent of the alkyl is selected from hydrogen, C1-C20 alkyl, C1-C20 haloalkyl, C1-C20 alkylcarbonyl, nitro, hydroxyl, ester, alkenyl, ether, amide, silicon-based, sulfhydryl, amino or cyano, the substituent of the alkyl is selected from C1-C20 alk