CN104193620A - Method for preparing alpha-hydroxyl-beta-dicarbonyl compound through activating oxygen in air by using hydrazine - Google Patents

Method for preparing alpha-hydroxyl-beta-dicarbonyl compound through activating oxygen in air by using hydrazine Download PDF

Info

Publication number
CN104193620A
CN104193620A CN201410353424.6A CN201410353424A CN104193620A CN 104193620 A CN104193620 A CN 104193620A CN 201410353424 A CN201410353424 A CN 201410353424A CN 104193620 A CN104193620 A CN 104193620A
Authority
CN
China
Prior art keywords
compound
heterocycles
yuan
cinchonine
alkyl
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
Application number
CN201410353424.6A
Other languages
Chinese (zh)
Inventor
孟庆伟
王亚坤
熊婷
房金海
杨帆
刘广志
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Dalian University of Technology
Original Assignee
Dalian University of Technology
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Dalian University of Technology filed Critical Dalian University of Technology
Priority to CN201410353424.6A priority Critical patent/CN104193620A/en
Publication of CN104193620A publication Critical patent/CN104193620A/en
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/31—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of functional groups containing oxygen only in singly bound form
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention relates to a method for preparing a compound I (the compound is achiral, racemized or enantiomer-enriched in the indicated hydroxylation center). The method comprises the steps of adding organic hydrazine and a compound II under the condition that alkali is used as a catalyst, and enabling the organic hydrazine and the compound II to be in contact with a gas containing oxygen molecules to obtain the compound I with the highest yield of 98%. The product obtained by carrying out mixed reaction in a solvent by taking chiral alkali such as cinchona alkaloid as a catalyst and the compound II as a substrate is used as the enantiomer-enriched compound I with the highest yield of 95% and the ee value of 85%. The solvent comprises halogenated hydrocarbon, aromatic hydrocarbon, alkane, ether solvents and the like. Molecular oxygen is activated by using organic hydrazine compounds to realize the alpha-hydroxylation reaction of a beta-dicarbonyl compound, so that the method is relatively high in atom economy and environment-friendly. The method is a novel method for preparing various chiral or achiral alpha-hydroxyl-beta-dicarbonyl compounds through activating molecular oxygen by using organic hydrazine compounds.

Description

Hydrazine activating air oxygen is prepared the method for ɑ-hydroxy-beta-dicarbonyl compound
Technical field
The invention belongs to technical field of organic synthesis, relate to the method that hydrazine activating air oxygen is prepared chirality and achirality ɑ-hydroxy-beta-dicarbonyl compound.
Technical background
Having optically active ɑ-hydroxy-beta-dicarbonyl compound is the very important structural unit of a class, is present in widely natural product, in chiral medicinal and pesticide intermediate.It is worth mentioning that, the chloro-1-oxo indenes-2-of (S)-5-hydroxyl-2-carboxylate methyl ester is the important intermediate of agricultural chemicals indoxacarb.It is that such structural unit of acquisition is the simplest that 1,3-dicarbonyl compound is carried out to direct asymmetric ɑ-hydroxylating, the most direct method.In the last few years, researchers had been reported the method for a large amount of asymmetric synthesis chirality ɑ-hydroxyl beta-dicarbonyl compounds, and these methods can be divided into two large classes: a) metal complex/active oxygen system.B) organic catalyst/active oxygen system.
For metal complex/active oxygen system, document (Proc.Natl.Acad.Sci.U.S.A.2004,101,5810 – 5814) reported that chiral ligand that tartrate is derivative and the metal complex of tetravalence Ti coordination are that catalyzer is prepared chirality ɑ-hydroxyl beta-dicarbonyl compound, but used catalyst and oxygenant are expensive, limited the application of the method.This is also the ubiquitous problem of metal coordination catalysis.Organic catalysis aspect, and document (J.Am.Chem.Soc.2009,128,16488-16489) reported the method with the derivative bronsted acid catalyst asymmetry catalysis ɑ-hydroxy-beta dicarbonyl compound of chiral phosphoric acid.The method can obtain the product (the highest 99%ee) of very high corresponding selection, but chiral phosphoric acid used is more difficult synthetic, expensive, and oxygenant nitrosobenzene toxicity is huge, is not suitable for industrial production.
It should be noted that molecular oxygen has obtained increasing chemists' attention in research in recent years, is a kind of ideal oxygenant, because its source widely, and 100% Atom economy.In the last few years, photo-oxidation (Photooxygenation) had become a kind of important method for oxidation, and the method realizes oxidising process by photoactivation molecular oxygen.Document (J.Am.Chem.Soc.2004,126,8914 – 8915) has been reported the asymmetric ɑ-hydroxylating of light-catalysed aldehyde ketone for the first time, uses amino acid as chiral catalyst, and tetraphenylporphyrin is photosensitizers, has obtained good effect.(Chem Asian J.2012 for document, 7,2019 – 2023) report the asymmetric ɑ-hydroxylating of the first light-catalysed beta-ketoester, used the derivative phase-transfer catalyst of quinine, under gentle condition, can obtain the oxidation products of medium enantioselectivity and high yield.In addition, document (Org.Lett.2008,10,1593 – 1595) has been reported triethyl-phosphite (P (OEt) 3) as auxiliary agent, molecular oxygen is the asymmetric ɑ-hydroxylating for producing oxindoles substrate as oxygenant.But because triethyl-phosphite/oxygen system Catalytic active phase is to lower, for substrate, the environmental requirements such as solvent are harsh, limited the application of the method.Although for the ɑ-hydroxylating of beta-dicarbonyl compound, scientists has been done a large amount of fruitful work, in this reaction, with molecular oxygen, as oxygenant, carrys out realization response process, remains a huge challenge.
Summary of the invention
The technical problem to be solved in the present invention is to provide the novel method that a kind of hydrazine activating air oxygen is prepared ɑ-hydroxy-beta-dicarbonyl compound, use hydrazine/alkali/contain oxygen molecule gas/solvent system, not only can prepare very efficiently racemic ɑ-hydroxy-beta-dicarbonyl compound, when exogenously added alkali is chiral gold Chinine, more can obtain the ɑ-hydroxy-beta-dicarbonyl compound of high enantioselectivity.
Hydrazine activating air oxygen is prepared a method for ɑ-hydroxy-beta-dicarbonyl compound, and concrete steps are as follows:
Take Compound I I as reaction raw materials, in solvent, alkali is under the condition of catalyzer, organic hydrazine is activator, makes Compound I I and contains molecular oxygen precursor and react, and temperature of reaction is-70 ℃～50 ℃, reaction times is 2 hours to 4 days, obtain Compound I, wherein, the consumption of alkali is 0.1 molar equivalent～3 molar equivalent of Compound I I; The chemical formula of Compound I and Compound I I is as follows:
Concrete synthesis path is as follows:
In Compound I and Compound I I:
* the chiral centre that represents Compound I;
R 1for hydrogen atom, alkoxyl group, alkyl, cycloalkyl, cycloalkyloxy, phenyl ring, phenoxy group ring, 5-aromatic heterocycle or 6-aromatic heterocycle;
R 2for hydrogen atom, alkyl, cycloalkyl, phenyl ring, 5-aromatic heterocycle or 6-aromatic heterocycle;
R 3for hydrogen atom, alkoxyl group, alkyl, cycloalkyl, cycloalkyloxy, phenyl ring, phenoxy group ring, 5-aromatic heterocycle or 6-aromatic heterocycle;
R 2and R 3form together the optional connection chain by 3-6 member composition replacing, comprising at least one carbon atom member, optionally comprise and be no more than two carbon members that exist with C=0 form, the member who optionally comprises a free nitrogen and oxygen, and optional with phenyl ring, 5-aromatic heterocycle or the fragrant heterocycle of 6-unit thick and, each encircles and is optionally substituted.
In Compound I and Compound I I:
R 1for alkoxyl group;
R 2for alkyl;
R 3for the optional phenyl replacing, or R 2and R 3can form together the connection chain by 3-4 carbon member composition of optional replacement, its optional and optional phenyl ring replacing thick and.
Compound I I is Compound I Ia:
Concrete synthesis path is as follows:
R 1for hydrogen atom, alkoxyl group, alkyl, cycloalkyl, cycloalkyloxy, phenyl ring, phenoxy group ring, 5-aromatic heterocycle or 6-aromatic heterocycle;
R 4for hydrogen atom, halogen tape base, alkyl, alkoxyl group, cycloalkyl, aromatic ring, Bian oxygen base, 5 yuan of heterocycles or 6 yuan of heterocycles;
R 5for hydrogen atom, halogen tape base, alkyl, alkoxyl group, cycloalkyl, aromatic ring, Bian oxygen base, 5 yuan of heterocycles or 6 yuan of heterocycles;
R 6for hydrogen atom, halogen tape base, alkyl, alkoxyl group, cycloalkyl, aromatic ring, Bian oxygen base, 5 yuan of heterocycles or 6 yuan of heterocycles;
R 7for hydrogen atom, halogen tape base, alkyl, alkoxyl group, cycloalkyl, aromatic ring, Bian oxygen base, 5 yuan of heterocycles or 6 yuan of heterocycles;
N is the natural number of 0-3.
The Formulae II I of described organic hydrazine is as follows:
Wherein, R 1for hydrogen atom, alkyl, cycloalkyl, alkoxyl group, aromatic ring, 5 yuan of heterocycles or 6 yuan of heterocycles;
R 2for alkyl, cycloalkyl, alkoxyl group, aromatic ring, 5 yuan of heterocycles or 6 yuan of heterocycles.
Described alkali is one or more mixing in sodium carbonate, salt of wormwood, cesium carbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium tert-butoxide, potassium tert.-butoxide, sodium hydride, sodium methylate, sodium ethylate.Described alkali is achirality organic bases, refers to triethylamine, one or more mixing in diisopropylethylamine, TERTIARY BUTYL AMINE, pyridine, piperidines, imidazoles, tetramethyl guanidine, diazabicylo, triethylene diamine; Described alkali is chirality organic bases, refers to that quinine cinchonine, cinchonine are fixed, quinine, Quinidine, dihydro cinchonine, dihydro cinchonine are fixed, one or more mixing in the derivative of hydroquinine, dihydrochinidin, dihydrochinidin.
Described solvent is one or more mixing in halohydrocarbon, aromatic hydrocarbon, alkane, ether;
Described halohydrocarbon is methylene dichloride, chloroform, tetracol phenixin, methylene bromide, glycol dibromide, 1, one or more mixing in 2-ethylene dichloride;
Described aromatic hydrocarbon is benzene, toluene, face one or more mixing in dimethylbenzene, m-xylene, p-Xylol, ditane, naphthane;
One or more mixing in described alkane normal hexane, hexanaphthene, ethane;
Described ether is one or more mixing in ether, diethylene glycol dimethyl ether, methyl tertiary butyl ether.
Formula Compound I be alkali at substrate 0.1 molar equivalent～5 molar equivalent as catalyzer, under optional inert solvent catalysis, through type Compound I I contacts with the hydrazine that is conventionally about 1-5 molar equivalent, uncovered reaction in containing molecular oxygen precursor and preparing.
Hydrazine class compound is preferably methyl hydrazine, phenylhydrazine, benzyl hydrazine or hydroxyethylhydrazine.
R in formula Compound I and Compound I I 1, R 2and R 3be and the additional group of hydroxylating center without direct relation.Because the reaction conditions of hydroxylacion method of the present invention is comparatively gentle, so R 1, R 2and R 3in can there is different kinds of molecules constitutional features, and only have the reactive functional group of the tool of oxidizing condition just easily influenced.Therefore, the listed R of summary of the invention part 1, R 2and R 3substituting group should think only to describe the subgroup of the extensive scope of application of explanation the inventive method.Although there is no clear and definite restriction to being applicable to the formula I of the inventive method and the size of II, it should be noted that these methods of the present invention, in formula Compound I and formula Compound I I, R 1for hydrogen atom, alkoxyl group, alkyl, cycloalkyl, cycloalkyloxy, phenyl ring, phenoxy group ring, 5-aromatic heterocycle or 6-aromatic heterocycle, they are optionally substituted separately; R 2for hydrogen atom, alkyl, cycloalkyl, phenyl ring, 5-aromatic heterocycle or 6-aromatic heterocycle, they are optionally substituted separately; R 3for hydrogen atom, alkoxyl group, alkyl, cycloalkyl, cycloalkyloxy, phenyl ring, phenoxy group ring, 5-aromatic heterocycle or 6-aromatic heterocycle, they are optionally substituted separately.
Preferred the inventive method comprises uses wherein R 1for alkyl and R 4, R 5, R 6, R 7for the formula IIa compound of alkoxyl group or hydrogen atom contacts with alkali with methyl hydrazine, the chiral centre indicating for the preparation of * is that racemize is revolved or the compound of the formula Ia of enantiomorph enrichment.
Most preferred method comprises contacts the derivative catalyzer of compound, methyl hydrazine and quinine of formula IIa.
The invention has the beneficial effects as follows: method of the present invention can obtain the formula Ia of high yield and enantiomeric excess, and reaction conditions is more gentle.Hydroxylacion method of the present invention is generally applicable to the initial compound of various formula II, and these compounds can utilize the known method in synthetic organic chemistry field to obtain.
Embodiment
Below in conjunction with technical scheme, describe specific embodiments of the invention in detail, make those skilled in the art better understand the present invention.
Embodiment 1 preparation 5-chlorine-2-hydroxyl-1-indone-2-methyl-formiate
Take substrate (22.4mg, 0.1mmol), cesium carbonate (32.5mg, 0.1mmol) and methyl hydrazine (12.0mg, 0.26mmol), add 4mL chloroform, at room temperature uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 12 hours, be spin-dried for solvent, by middle compacting, standby (silicagel column, PE/EtOAc=5/1), obtains target product, white solid (21.0mg, 88% yield).
Embodiment 2 preparation 5-chlorine-2-hydroxyl-1-indone-2-methyl-formiates
Take substrate (22.4mg, 0.1mmol), tetramethyl guanidine (11.5mg, 0.1mmol) and methyl hydrazine (12.0mg, 0.26mmol), add 4mL chloroform, at room temperature uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 6 hours, be spin-dried for solvent, by middle compacting, standby (silicagel column, PE/EtOAc=5/1), obtains target product, white solid (20.3mg, 88%yield).
Embodiment 3 preparation (S)-5-chlorine-2-hydroxyl-1-indone-2-methyl-formiates
Take substrate (22.4mg, 0.1mmol), cinchonine (11.7mg, 0.04mmol) and methyl hydrazine (6.0mg, 0.13mmol) and be put in reaction flask, add 4mL chloroform.It is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting standby (silicagel column, PE/EtOAc=5/1), obtains target product, white solid (19.4mg, 81% yield, 51%ee).
Embodiment 3: preparation (S)-5-chlorine-2-hydroxyl-1-indone-2-methyl-formiate
Take substrate (22.4mg, 0.1mmol), dihydro cinchonine (11.7mg, 0.04mmol) and methyl hydrazine (6.0mg, 0.13mmol) and be put in reaction flask, add 4mL chloroform.It is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting standby (silicagel column, PE/EtOAc=5/1), obtains target product, white solid (19.8mg, 83% yield, 53%ee).
Embodiment 4 preparation (R)-5-chlorine-2-hydroxyl-1-indone-2-methyl-formiates
Take substrate (22.4mg, 0.1mmol), quinine (12.9mg, 0.04mmol) and methyl hydrazine (6.0mg, 0.13mmol) and be put in reaction flask, add 4mL chloroform.It is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting standby (silicagel column, PE/EtOAc=5/1), obtains target product, white solid (19.4mg, 81% yield, 64%ee).
Embodiment 5 preparation (R)-5-chlorine-2-hydroxyl-1-indone-2-methyl-formiates
Take substrate (22.4mg, 0.1mmol), hydroquinine (13.0mg, 0.04mmol) and methyl hydrazine (6.0mg, 0.13mmol) and be put in reaction flask, add 4mL chloroform.It is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting, standby (silicagel column, PE/EtOAc=5/1), obtains target product, white solid (20.3mg, 85% yield); [α] d 25-61.5 (c0.07, CHCl 3, 67%ee); Mp134-136 ℃; 1h NMR (500MHz, CDCl 3) δ 7.74 (d, J=8.2Hz, 1H), 7.50 (d, J=0.7Hz, 1H), 7.43 (dd, J=8.2,0.8Hz, 1H), 3.75 (s, 3H), 3.71 (d, J=17.4Hz, 1H), 3.24 (d, J=17.4Hz, 1H); HPLC conditions:Chiralcel OD-H column (250 * 4.6mm), hexane/i-PrOH=90/10,1mL/min, 254nm, τ r(major)=10.4min, τ r(minor)=8.8min.
Embodiment 6 preparation (R)-5-chlorine-2-hydroxyl-1-indone-2-methyl-formiates
Take substrate (22.4mg, 0.1mmol), hydroquinine (13.0mg, 0.04mmol) and 2-hydroxyethylhydrazine (9.9mg, 0.13mmol) and be put in reaction flask, add 4mL chloroform.It is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting standby (silicagel column, PE/EtOAc=5/1), obtains target product, white solid (19.9mg, 83% yield, 63%ee).
Embodiment 7 preparation (R)-5-chlorine-2-hydroxyl-1-indone-2-methyl-formiates
Take substrate (22.4mg, 0.1mmol), hydroquinine (13.0mg, 0.04mmol) and phenylhydrazine (14.0mg, 0.13mmol) and be put in reaction flask, add 4mL chloroform.It is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting standby (silicagel column, PE/EtOAc=5/1), obtains target product, white solid (15.6mg, 65% yield, 53%ee).
Embodiment 8 preparation (R)-5-chlorine-2-hydroxyl-1-indone-2-methyl-formiates
Take substrate (22.4mg, 0.1mmol), hydroquinine (13.0mg, 0.04mmol) and benzyl hydrazine (15.9mg, 0.13mmol) and be put in reaction flask, add 4mL chloroform.It is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting standby (silicagel column, PE/EtOAc=5/1), obtains target product, white solid (19.4mg, 81% yield, 61%ee).
Embodiment 9 preparation (R)-5-chlorine-2-hydroxyl-1-indone-2-methyl-formiates
Take substrate (22.4mg, 0.1mmol), hydroquinine (13.0mg, 0.04mmol) and phenylbenzene azo carbohydrazide (31.2mg, 0.13mmol) and be put in reaction flask, add 4mL chloroform.It is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting standby (silicagel column, PE/EtOAc=5/1), obtains target product, white solid (12.2mg, 51% yield, 58%ee).
Embodiment 10 preparation 6-methyl-2-hydroxide radical-1-indenone-2-methyl-formiates
Take substrate (20.4mg, 0.1mmol), hydroquinine (13.0mg, 0.04mmol) and methyl hydrazine (6.0mg, 0.13mmol) and be put in reaction flask, add chloroform 4mL, it is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting, standby (silicagel column, PE/EtOAc=5/1), obtains target product, white solid (17.2mg, 78% yield); [α] d 25-46.2 (c0.04, CHCl 3, 65%ee); Mp132-134 ℃; 1h NMR (500MHz, CDCl 3) δ 7.60 (s, 1H), 7.50 (d, J=7.8Hz, 1H), 7.38 (d, J=7.8Hz, 1H), 3.74 (s, 3H), 3.68 (d, J=17.1Hz, 1H), 3.21 (d, J=17.1Hz, 1H), 2.42 (s, 3H); HPLC conditions:Chiralcel OD-H column (250 * 4.6mm), hexane/i-PrOH=90/10,1mL/min, 254nm, τ r(major)=12.4min, τ r(minor)=10.7min.
Embodiment 11 preparation 6-methoxyl group-2-hydroxide radical-1-indenone-2-methyl-formiates
Take substrate (22.0mg, 0.1mmol), hydroquinine (13.0mg, 0.04mmol) and methyl hydrazine (6.0mg, 0.13mmol) and be put in reaction flask, add chloroform 4mL, it is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting, standby (silicagel column, PE/EtOAc=5/1), obtains target product, yellow solid (16.3mg, 69% yield); [α] d 25-38.6 (c0.06, CHCl 3, 78%ee); Mp118-120 ℃; 1h NMR (500MHz, CDCl 3) δ 7.39 (d, J=8.3Hz, 1H), 7.28 (m, 1H), 7.21 (d, J=8.6Hz, 1H), 3.84 (s, 3H), 3.75 (s, 3H), 3.65 (d, J=16.9Hz, 1H), 3.18 (d, J=16.9Hz, 1H); HPLC conditions:Chiralcel OD-H column (250 * 4.6mm), hexane/i-PrOH=90/10,1mL/min, 254nm, τ r(major)=15.6min, τ r(minor)=13.8min.
The fluoro-2-hydroxide radical-1-indenone-2-of embodiment 12 preparation 6-methyl-formiate
Take substrate (20.8mg, 0.1mmol), hydroquinine (13.0mg, 0.04mmol) and methyl hydrazine (6.0mg, 0.13mmol) and be put in reaction flask, add chloroform 4mL, it is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting, standby (silicagel column, PE/EtOAc=5/1), obtains target product, white solid (18.0mg, 81%yield); [α] d 25-46.5 (c0.09, CHCl 3, 67%ee); Mp130-132 ℃; 1h NMR (500MHz, CDCl 3) δ 7.56 – 7.35 (m, 3H), 3.76 (s, 3H), 3.69 (d, J=17.1Hz, 1H), 3.22 (d, J=17.1Hz, 1H); HPLC conditions:Chiralcel OD-H column (250 * 4.6mm), hexane/i-PrOH=90/10,1mL/min, 254nm, τ r(major)=13.0min, τ r(minor)=10.9min.
The bromo-2-hydroxide radical-1-indenone-2-of embodiment 13 preparation 6-methyl-formiate
Take substrate (26.9mg, 0.1mmol), hydroquinine (13.0mg, 0.04mmol) and methyl hydrazine (6.0mg, 0.13mmol) and be put in reaction flask, add chloroform 4mL, it is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting, standby (silicagel column, PE/EtOAc=5/1), obtains target product, yellow solid (24.1mg, 85% yield); [α] d 25-28.3 (c0.10, CHCl 3, 64%ee); Mp119-121 ℃; 1h NMR (500MHz, CDCl 3) δ 7.92 (d, J=1.8Hz, 1H), 7.78 (dd, J=8.2,1.9Hz, 1H), 7.39 (d, J=8.2Hz, 1H), 3.75 (s, 3H), 3.67 (d, J=17.4Hz, 1H), 3.20 (d, J=17.4Hz, 1H); HPLC conditions:Chiralcel OD-H column (250 * 4.6mm), hexane/i-PrOH=90/10,1mL/min, 254nm, τ r(major)=14.1min, τ r(minor)=11.8min.
Embodiment 14 preparation 2-hydroxide radical-1-indenone-2-methyl-formiates
Take substrate (18.9mg, 0.1mmol), hydroquinine (13.0mg, 0.04mmol) and methyl hydrazine (6.0mg, 0.13mmol) and be put in reaction flask, add chloroform 4mL, it is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting, standby (silicagel column, PE/EtOAc=5/1), obtains target product, white solid (16.7mg, 82% yield); [α] d 25-56.1 (c0.08, CHCl 3, 68%ee); Mp134-136 ℃; 1h NMR (500MHz, CDCl 3) δ 7.81 (d, J=7.7Hz, 1H), 7.68 (t, J=7.5Hz, 1H), 7.50 (d, J=7.7Hz, 1H), 7.44 (t, J=7.5Hz, 1H), 3.78 – 3.69 (m, 4H), 3.26 (d, J=17.2Hz, 1H); HPLC conditions:Chiralcel OD-H column (250 * 4.6mm), hexane/i-PrOH=80/20,1mL/min, 254nm, τ r(major)=9.2min, τ r(minor)=8.0min.
Embodiment 15 preparation 5-bromine 2-hydroxide radical-1-indenone-2-methyl-formiates
Take substrate (26.9mg, 0.1mmol), hydroquinine (13.0mg, 0.04mmol) and methyl hydrazine (6.0mg, 0.13mmol) and be put in reaction flask, add chloroform 4mL, it is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting, standby (silicagel column, PE/EtOAc=5/1), obtains target product, white solid (21.3mg, 75% productive rate); [α] d 25-63.1 (c0.08, CHCl 3, 66%ee); Mp126-128 ℃; 1h NMR (500MHz, CDCl 3) δ 7.74 – 7.63 (m, 2H), 7.58 (dd, J=8.2,0.6Hz, 1H), 3.75 (s, 3H), 3.70 (d, J=17.4Hz, 1H), 3.24 (d, J=17.4Hz, 1H); HPLC conditions:Chiralcel OD-H column (250 * 4.6mm), hexane/i-PrOH=90/10,1mL/min, 254nm, τ r(major)=15.8min, τ r(minor)=13.4min.
Embodiment 16 preparation 4-methoxyl group-2-hydroxide radical-1-indenone-2-methyl-formiates
Take substrate (22.0mg, 0.1mmol), hydroquinine (13.0mg, 0.04mmol) and methyl hydrazine (6.0mg, 0.13mmol) be put in reaction flask, the chloroformic solution 2mL that adds 0.065mol/L methyl hydrazine, add chloroform 2mL, it is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air again.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting, standby (silicagel column, PE/EtOAc=5/1), obtains target product, white solid (16.7mg, 71% yield); [α] d 25-45.7 (c0.07, CHCl 3, 67%ee); Mp141-143 ℃; 1h NMR (500MHz, CDCl 3) δ 7.47 – 7.35 (m, 2H), 7.12 (d, J=7.1Hz, 1H), 3.92 (s, 3H), 3.74 (s, 3H), 3.66 (d, J=17.7Hz, 1H), 3.12 (d, J=17.7Hz, 1H); HPLC conditions:ChiralcelOD-H column (250 * 4.6mm), hexane/i-PrOH=90/10,1mL/min, 254nm, τ r(major)=14.2min, τ r(minor)=16.0min.
Embodiment 17 preparation 2-hydroxide radical-1-indenone-2-ethyl formates
Take substrate (20.4mg, 0.1mmol), hydroquinine (13.0mg, 0.04mmol) and methyl hydrazine (6.0mg, 0.13mmol) and be put in reaction flask, add chloroform 4mL, it is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting, standby (silicagel column, PE/EtOAc=5/1), obtains target product, colourless liquid (15.8mg, 72% yield); [α] d 25-41.5 (c0.14, CHCl 3, 66%ee); 1h NMR (500MHz, CDCl 3) δ 7.81 (d, J=7.7Hz, 1H), 7.68 (td, J=7.6,1.1Hz, 1H), 7.50 (d, J=7.7Hz, 1H), 7.47 – 7.41 (m, 1H), 4.30 – 4.13 (m, 2H), 3.73 (d, J=17.2Hz, 1H), 3.26 (d, J=17.2Hz, 1H), 1.19 (t, J=7.1Hz, 3H); HPLC conditions:Chiralcel OD-H column (250 * 4.6mm), hexane/i-PrOH=90/10,1mL/min, 254nm, τ r(major)=11.0min, τ r(minor)=9.6min.
Embodiment 18 preparation α, α-diethyl-propyl group-2-hydroxide radical-1-indenone-manthanoate
Take substrate (27.4mg, 0.1mmol), hydroquinine (13.0mg, 0.04mmol) and methyl hydrazine (6.0mg, 0.13mmol) and be put in reaction flask, add chloroform 4mL, it is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting, standby (silicagel column, PE/EtOAc=5/1), obtains target product, colorless oil (19.4mg, 67% yield); [α] d 25-23.5 (c0.05, CHCl 3, 75%ee); 1h NMR (500MHz, CDCl 3) δ 7.80 (d, J=7.7Hz, 1H), 7.65 (td, J=7.6,1.1Hz, 1H), 7.48 (d, J=7.7Hz, 1H), 7.42 (t, J=7.5Hz, 1H), 4.04 (s, 1H), 3.64 (d, J=17.0Hz, 1H), 3.26 (d, J=17.0Hz, 1H), 1.70 (q, J=7.5Hz, 6H), 0.65 (t, J=7.5Hz, 9H); HPLC conditions:Chiralcel AS-H column (250 * 4.6mm), hexane/i-PrOH=80/20,1mL/min, 254nm, τ r(major)=9.1min, τ r(minor)=10.9min.
Embodiment 19 preparation 2-hydroxide radical-1-indenone-2-isopropyl formates
Take substrate (21.8mg, 0.1mmol), hydroquinine (13.0mg, 0.04mmol) and methyl hydrazine (6.0mg, 0.13mmol) and be put in reaction flask, add chloroform 4mL, it is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting, standby (silicagel column, PE/EtOAc=5/1), obtains target product, white solid (17.0mg, 73% yield); [α] d 25-30.9 (c0.06, CHCl 3, 61%ee); Mp68-74 ℃; 1h NMR (500MHz, CDCl 3) δ 7.80 (d, J=7.7Hz, 1H), 7.67 (td, J=7.6,1.0Hz, 1H), 7.49 (d, J=7.7Hz, 1H), 7.43 (dd, J=11.1,3.9Hz, 1H), 5.19 – 4.94 (m, 1H), 3.70 (d, J=17.2Hz, 1H), 3.24 (d, J=17.2Hz, 1H), 1.20 (d, J=6.3Hz, 3H), 1.13 (d, J=6.3Hz, 3H); HPLC conditions:Chiralcel OD-H column (250 * 4.6mm), hexane/i-PrOH=90/10,1mL/min, 254nm, τ r(major)=8.7min, τ r(minor)=7.8min.
Embodiment 20 2-hydroxide radical-1-indenone-2-t-butyl formates
Take substrate (23.1mg, 0.1mmol), hydroquinine (13.0mg, 0.04mmol) and methyl hydrazine (6.0mg, 0.13mmol) be put in reaction flask, the chloroformic solution 2mL that adds 0.065mol/L methyl hydrazine, add chloroform 2mL, it is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air again.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting, standby (silicagel column, PE/EtOAc=5/1), obtains target product, white solid (19.2mg, 78% yield); [α] d 25-29.5 (c0.06, CHCl 3, 58%ee); Mp128-129 ℃; 1h NMR (500MHz, CDCl 3) δ 7.79 (d, J=7.7Hz, 1H), 7.64 (d, J=7.5Hz, 1H), 7.48 (d, J=7.7Hz, 1H), 7.42 (t, J=7.5Hz, 1H), 3.65 (d, J=17.1Hz, 1H), 3.22 (d, J=17.1Hz, 1H), 1.36 (s, 9H); HPLC conditions:Chiralcel OD-H column (250 * 4.6mm), hexane/i-PrOH=90/10,1mL/min, 254nm, τ r(major)=6.8min, τ r(minor)=6.3min.
Embodiment 21 2-hydroxide radical-1-indenone-2-benzyl formates
Take substrate (26.6mg, 0.1mmol), hydroquinine (13.0mg, 0.04mmol) and methyl hydrazine (6.0mg, 0.13mmol) and be put in reaction flask, add chloroform 4mL, it is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting, standby (silicagel column, PE/EtOAc=5/1), obtains target product, colorless solid (21.0mg, 75% yield); [α] d 26-47.6 (c0.04, CHCl 3, 60%ee); Mp94-97 ℃; 1h NMR (500MHz, CDCl3) δ 7.80 (d, J=7.7Hz, 1H), 7.65 (t, J=7.2Hz, 1H), 7.50 – 7.39 (m, 2H), 7.33 – 7.26 (m, 3H), 7.14 (dd, J=6.5,2.8Hz, 2H), 5.22 (d, J=12.4Hz, 1H), 5.12 (d, J=12.4Hz, 1H), 3.72 (d, J=17.2Hz, 1H), 3.25 (d, J=17.2Hz, 1H); HPLC conditions:Chiralcel OD-H column (250 * 4.6mm), hexane/i-PrOH=90/10,1mL/min, 254nm, τ r(major)=19.1min, τ r(minor)=15.9min.
Embodiment 22 2-hydroxide radical-1-indenone-2-formic acid Buddha's warrior attendant esters
Take substrate (31.0mg, 0.1mmol), hydroquinine (13.0mg, 0.04mmol) and methyl hydrazine (6.0mg, 0.13mmol) and be put in reaction flask, add chloroform 4mL, it is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting, standby (silicagel column, PE/EtOAc=5/1), obtains target product, colorless oil (23.0mg, 71% yield); [α] d 25-25.0 (c0.05, CHCl 3, 66%ee); 1h NMR (500MHz, CDCl 3) δ 7.79 (d, J=7.7Hz, 1H), 7.65 (td, J=7.6,1.1Hz, 1H), 7.48 (d, J=7.7Hz, 1H), 7.42 (t, J=7.5Hz, 1H), 3.66 (d, J=17.1Hz, 1H), 3.22 (d, J=17.1Hz, 1H), 2.12 (s, 3H), 1.96 (d, J=3.1Hz, 6H), 1.60 (d, J=2.6Hz, 6H); HPLC conditions:Chiralcel AD-H column (250 * 4.6mm), hexane/i-PrOH=90/10,1mL/min, 254nm, τ r(major)=18.2min, τ r(minor)=11.3min.
Embodiment 23 Alpha-Methyls-α-phenyl-benzyl-2-hydroxide radical-1-indenone-manthanoate
Take substrate (35.6mg, 0.1mmol), hydroquinine (13.0mg, 0.04mmol) and methyl hydrazine (6.0mg, 0.13mmol) and be put in reaction flask, add chloroform 4mL, it is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting, standby (silicagel column, PE/EtOAc=5/1), obtains target product, white solid (35.3mg, 95% yield); [α] d 25-61.5 (c0.12, CHCl 3, 85%ee); Mp90-92 ℃; 1h NMR (400MHz, DMSO) δ 7.90 – 7.78 (m, 2H), 7.70 (d, J=7.7Hz, 1H), 7.57 (t, J=7.4Hz, 1H), 7.23 – 7.07 (m, 6H), 7.02 – 6.85 (m, 4H), 6.69 (bs, 1H), 3.76 (d, J=17.4Hz, 1H), 3.20 (d, J=17.4Hz, 1H), 2.08 (s, 3H); HPLC conditions:Chiralcel OD-H column (250 * 4.6mm), hexane/i-PrOH=90/10,1mL/min, 254nm, τ r(major)=19.9min, τ r(minor)=15.41min.
Embodiment 24 2-hydroxide radical-1-indenone-2-formic acid-(2', 7'-dibromo)-9'-fluorenes ester
Take substrate (51.2mg, 0.1mmol), hydroquinine (13.0mg, 0.04mmol) and methyl hydrazine (6.0mg, 0.13mmol) and be put in reaction flask,, add chloroform 4mL, it is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting, standby (silicagel column, PE/EtOAc=5/1), obtains target product, white solid (43.2mg, 82% yield); [α] d 25-18.8 (c0.05, CHCl 3, 73%ee); Mp168-172 ℃; 1h NMR (500MHz, CDCl 3) δ 7.83 (d, J=7.7Hz, 1H), 7.64 (dd, J=13.0,5.1Hz, 2H), 7.56 – 7.52 (m, 1H), 7.49 (dd, J=8.1,1.5Hz, 1H), 7.43 (m, 5H), 6.66 (s, 1H), 3.76 (d, J=17.2Hz, 1H), (3.31 d, J=17.2Hz, 1H); HPLC conditions:Chiralcel OD-H column (250 * 4.6mm), hexane/i-PrOH=90/10,1mL/min, 254nm, τ r(major)=21.9min, τ r(minor)=18.6min.
Embodiment 25 preparation 2-hydroxide radical-1-indenone-2-formic acid-9'-methyl anthracene esters
Take substrate (36.6mg, 0.1mmol), hydroquinine (13.0mg, 0.04mmol) and methyl hydrazine (6.0mg, 0.13mmol) and be put in reaction flask, add chloroform 4mL, it is 15 ℃ that temperature of reaction is controlled, uncovered stirring reaction in air.In reaction process, by TLC (thin-layer chromatographic analysis), observe substrate conversion situation.React after 24 hours, be spin-dried for solvent, by middle compacting, standby (silicagel column, PE/EtOAc=5/1), obtains target product, yellow solid (30.8mg, 81% yield); [α] d 25-20.0 (c0.16, CHCl 3, 72%ee); Mp111-113 ℃; 1h NMR (500MHz, CDCl 3) δ 8.45 (s, 1H), 8.12 (d, J=8.1Hz, 2H), 8.05 – 7.93 (m, 2H), 7.70 (d, J=7.6Hz, 1H), 7.53 (t, J=7.5Hz, 1H), 7.50 – 7.42 (m, 4H), 7.33 (t, J=7.5Hz, 1H), 7.29 – 7.23 (m, 1H), 6.36 (d, J=12.6Hz, 1H), 6.00 (d, J=12.6Hz, 1H), 3.49 (d, J=17.1Hz, 1H), 3.11 (d, J=17.1Hz, 1H); HPLCconditions:Chiralcel OD-H column (250 * 4.6mm), hexane/i-PrOH=90/10,1mL/min, 254nm, τ r(major)=31.7min, τ r(minor)=25.3min..

Claims (10)

1. hydrazine activating air oxygen is prepared a method for ɑ-hydroxy-beta-dicarbonyl compound, it is characterized in that, step is as follows:
Take Compound I I as reaction raw materials, and in solvent, alkali is catalyzer, organic hydrazine is activator, makes Compound I I and contains molecular oxygen precursor and react, and temperature of reaction is-70 ℃～50 ℃, the consumption of alkali is 0.1 molar equivalent～3 molar equivalent of Compound I I, obtains Compound I; The chemical formula of Compound I and Compound I I is as follows:
In Compound I and Compound I I:
* the chiral centre that represents Compound I;
R 1for hydrogen atom, alkoxyl group, alkyl, cycloalkyl, cycloalkyloxy, phenyl ring, phenoxy group ring, 5-aromatic heterocycle or 6-aromatic heterocycle;
R 2for hydrogen atom, alkyl, cycloalkyl, phenyl ring, 5-aromatic heterocycle or 6-aromatic heterocycle;
R 3for hydrogen atom, alkoxyl group, alkyl, cycloalkyl, cycloalkyloxy, phenyl ring, phenoxy group ring, 5-aromatic heterocycle or 6-aromatic heterocycle;
R 2and R 3the common connection chain by 3-6 member composition that forms optional above-mentioned replacement, comprising at least one carbon atom member, optionally comprise and be no more than two carbon members that exist with C=0 form, the member who optionally comprises a free nitrogen and oxygen, and optional with phenyl ring, 5-aromatic heterocycle or the fragrant heterocycle of 6-unit thick and, each encircles and is optionally substituted.
2. method according to claim 1, is characterized in that, in Compound I and Compound I I:
R 1for alkoxyl group;
R 2for alkyl;
R 3for the optional phenyl replacing, or R 2and R 3common form the optional connection chain by 3-4 carbon member composition replacing, its optional and optional phenyl ring replacing thick and.
3. method according to claim 2, is characterized in that, wherein Compound I I is Compound I Ia:
R 1for hydrogen atom, alkoxyl group, alkyl, cycloalkyl, cycloalkyloxy, phenyl ring, phenoxy group ring, 5-aromatic heterocycle or 6-aromatic heterocycle;
R 4for hydrogen atom, halogen tape base, alkyl, alkoxyl group, cycloalkyl, aromatic ring, Bian oxygen base, 5 yuan of heterocycles or 6 yuan of heterocycles;
R 5for hydrogen atom, halogen tape base, alkyl, alkoxyl group, cycloalkyl, aromatic ring, Bian oxygen base, 5 yuan of heterocycles or 6 yuan of heterocycles;
R 6for hydrogen atom, halogen tape base, alkyl, alkoxyl group, cycloalkyl, aromatic ring, Bian oxygen base, 5 yuan of heterocycles or 6 yuan of heterocycles;
R 7for hydrogen atom, halogen tape base, alkyl, alkoxyl group, cycloalkyl, aromatic ring, Bian oxygen base, 5 yuan of heterocycles or 6 yuan of heterocycles;
N is the natural number of 0-3.
4. according to the arbitrary described method of claim 1-3, be further characterized in that, the Formulae II I of described organic hydrazine is as follows:
Wherein, R 1for hydrogen atom, alkyl, cycloalkyl, alkoxyl group, aromatic ring, 5 yuan of heterocycles or 6 yuan of heterocycles;
R 2for alkyl, cycloalkyl, alkoxyl group, aromatic ring, 5 yuan of heterocycles or 6 yuan of heterocycles.
5. according to the arbitrary described method of claim 1-3, be further characterized in that, described alkali is one or more mixing in sodium carbonate, salt of wormwood, cesium carbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium tert-butoxide, potassium tert.-butoxide, sodium hydride, sodium methylate, sodium ethylate.
6. method according to claim 4, be further characterized in that, described alkali is one or more mixing in sodium carbonate, salt of wormwood, cesium carbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium tert-butoxide, potassium tert.-butoxide, sodium hydride, sodium methylate, sodium ethylate.
7. according to the method described in claim 1,2,3 or 6, it is characterized in that, described alkali is achirality organic bases, refers to triethylamine, one or more mixing in diisopropylethylamine, TERTIARY BUTYL AMINE, pyridine, piperidines, imidazoles, tetramethyl guanidine, diazabicylo, triethylene diamine; Described alkali is chirality organic bases, refers to that quinine cinchonine, cinchonine are fixed, quinine, Quinidine, dihydro cinchonine, dihydro cinchonine are fixed, one or more mixing in the derivative of hydroquinine, dihydrochinidin, dihydrochinidin.
8. method according to claim 4, it is characterized in that, described alkali is achirality organic bases, refers to triethylamine, one or more mixing in diisopropylethylamine, TERTIARY BUTYL AMINE, pyridine, piperidines, imidazoles, tetramethyl guanidine, diazabicylo, triethylene diamine; Described alkali is chirality organic bases, refers to that quinine cinchonine, cinchonine are fixed, quinine, Quinidine, dihydro cinchonine, dihydro cinchonine are fixed, one or more mixing in the derivative of hydroquinine, dihydrochinidin, dihydrochinidin.
9. method according to claim 5, it is characterized in that, described alkali is achirality organic bases, refers to triethylamine, one or more mixing in diisopropylethylamine, TERTIARY BUTYL AMINE, pyridine, piperidines, imidazoles, tetramethyl guanidine, diazabicylo, triethylene diamine; Described alkali is chirality organic bases, refers to that quinine cinchonine, cinchonine are fixed, quinine, Quinidine, dihydro cinchonine, dihydro cinchonine are fixed, one or more mixing in the derivative of hydroquinine, dihydrochinidin, dihydrochinidin.
10. according to the method described in claim 1,2,3,6,8 or 9, it is characterized in that, described solvent is one or more mixing in halohydrocarbon, aromatic hydrocarbon, alkane, ether;
Described halohydrocarbon is methylene dichloride, chloroform, tetracol phenixin, methylene bromide, glycol dibromide and 1,2-ethylene dichloride;
Described aromatic hydrocarbon is benzene, toluene, face dimethylbenzene, m-xylene, p-Xylol, ditane and naphthane;
Described alkane normal hexane, hexanaphthene and ethane;
Described ether is ether, diethylene glycol dimethyl ether and methyl tertiary butyl ether.
CN201410353424.6A 2014-07-23 2014-07-23 Method for preparing alpha-hydroxyl-beta-dicarbonyl compound through activating oxygen in air by using hydrazine Pending CN104193620A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201410353424.6A CN104193620A (en) 2014-07-23 2014-07-23 Method for preparing alpha-hydroxyl-beta-dicarbonyl compound through activating oxygen in air by using hydrazine

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201410353424.6A CN104193620A (en) 2014-07-23 2014-07-23 Method for preparing alpha-hydroxyl-beta-dicarbonyl compound through activating oxygen in air by using hydrazine

Publications (1)

Publication Number Publication Date
CN104193620A true CN104193620A (en) 2014-12-10

Family

ID=52079032

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201410353424.6A Pending CN104193620A (en) 2014-07-23 2014-07-23 Method for preparing alpha-hydroxyl-beta-dicarbonyl compound through activating oxygen in air by using hydrazine

Country Status (1)

Country Link
CN (1) CN104193620A (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105732387A (en) * 2016-04-14 2016-07-06 大连理工大学 Novel method for asymmetric alpha-hydroxylation of photo-oxygenation beta-dicarbonyl compound based on C-2' phase transfer catalyst
CN105969815A (en) * 2016-06-07 2016-09-28 苏州汉酶生物技术有限公司 Biological preparation method of (S)-5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic methyl ester
CN106397198A (en) * 2016-08-31 2017-02-15 京博农化科技股份有限公司 Preparation method of 5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic acid methyl ester
CN108821976A (en) * 2018-08-24 2018-11-16 吉林大学 A kind of method of indenone -2- formic acid esters catalysis oxidation under the conditions of micro- reaction condition or popular response
CN108911980A (en) * 2018-08-24 2018-11-30 吉林大学 The method that Kinetic Resolution is carried out to Alpha-hydroxy-beta-dicarbonyl compound enantiomer under the conditions of micro- reaction condition or popular response

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103254082A (en) * 2013-04-27 2013-08-21 大连理工大学 Method for preparing chiral alpha-hydroxyl-beta-dicarbonyl compound by using air oxygen as oxidant
CN103333069A (en) * 2013-06-10 2013-10-02 大连理工大学 Preparation method of alpha-hydroxy-beta-dicarbonyl compound using cinchona alkaloid derivative as catalyst

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103254082A (en) * 2013-04-27 2013-08-21 大连理工大学 Method for preparing chiral alpha-hydroxyl-beta-dicarbonyl compound by using air oxygen as oxidant
CN103333069A (en) * 2013-06-10 2013-10-02 大连理工大学 Preparation method of alpha-hydroxy-beta-dicarbonyl compound using cinchona alkaloid derivative as catalyst

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HIROYUKI KAWAI ET AL.,: "Enantioselective Synthesis of Epoxides Having a Tetrasubstituted Trifluoromethylated Carbon Center: Methylhydrazine-Induced Aerobic Epoxidation of b,b-Disubstituted Enones", 《ANGEW. CHEM. INT. ED.》, vol. 52, 21 January 2013 (2013-01-21) *
王亚坤等: "甲基肼引导的β-酮酸酯不对称α-羟基化研究", 《中国化学会第29届学术年会摘要集-28分会：绿色化学》, 14 July 2014 (2014-07-14) *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105732387A (en) * 2016-04-14 2016-07-06 大连理工大学 Novel method for asymmetric alpha-hydroxylation of photo-oxygenation beta-dicarbonyl compound based on C-2' phase transfer catalyst
CN105732387B (en) * 2016-04-14 2019-03-05 大连理工大学 The method of novel C -2` phase transfer catalyst photooxidation beta-dicarbonyl compound asymmetry 'alpha '-hydroxylation
CN105969815A (en) * 2016-06-07 2016-09-28 苏州汉酶生物技术有限公司 Biological preparation method of (S)-5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic methyl ester
CN106397198A (en) * 2016-08-31 2017-02-15 京博农化科技股份有限公司 Preparation method of 5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylic acid methyl ester
CN108821976A (en) * 2018-08-24 2018-11-16 吉林大学 A kind of method of indenone -2- formic acid esters catalysis oxidation under the conditions of micro- reaction condition or popular response
CN108911980A (en) * 2018-08-24 2018-11-30 吉林大学 The method that Kinetic Resolution is carried out to Alpha-hydroxy-beta-dicarbonyl compound enantiomer under the conditions of micro- reaction condition or popular response

Similar Documents

Publication Publication Date Title
Jin et al. Copper-catalysed addition of α-alkyl azaarenes to ethyl glyoxylate via direct C (sp 3)–H activation
Matsui et al. Conformational lock in a Brønsted acid–Lewis base organocatalyst for the aza-Morita–Baylis–Hillman reaction
CN104193620A (en) Method for preparing alpha-hydroxyl-beta-dicarbonyl compound through activating oxygen in air by using hydrazine
CN105732387B (en) The method of novel C -2` phase transfer catalyst photooxidation beta-dicarbonyl compound asymmetry 'alpha '-hydroxylation
US9334297B2 (en) Chiral imidazolium salts for asymmetric catalysis
CN105521826A (en) Zirconium catalyst and method for preparing chiral alpha-hydroxy-beta-keto ester compound by use of zirconium catalyst
Chen et al. Metal-free intramolecular carbocyanation of activated alkenes: functionalized nitriles bearing β-quaternary carbon centers.
Chen et al. Enantioselective synthesis of chiral phosphonylated 2, 3-dihydrofurans by copper catalyzed asymmetric formal [3+ 2] cycloaddition of propargylic esters with β-keto phosphonates
CN108516937A (en) A kind of method that visible light-initiated aerobic Salan- copper catalysts prepare chiral alpha-hydroxy-beta -one ester compound
Jeong et al. Synthesis of sterically controlled chiral β-amino alcohols and their application to the catalytic asymmetric sulfoxidation of sulfides
CN108059591B (en) Catalytic asymmetric synthesis method of chiral α -fluoro- β -ethynyl ketone compound
CN110343040A (en) A method of preparing the first chrysanthemumic acid of chiral trans
Ge et al. Enantio-and Z-selective synthesis of functionalized alkenes bearing tertiary allylic stereogenic center
CN107721858B (en) Method for catalyzing asymmetric alpha-benzoylation of beta-keto ester by phase transfer
Wakita et al. Enantioselective glyoxylate-ene reaction using a novel spiro bis (isoxazoline) ligand in copper catalysis
CN109438322A (en) One kind 4 '-trifluoromethyl -3,5 '-oxazolidinyl loop coil Oxoindole compound chiral method for preparing
Kawasaki et al. Asymmetric autocatalysis induced by octahedral tris (acetylacetonato) chromium (III) complex as a homogeneous chiral initiator
Yu et al. A versatile approach to functionalized cyclic ketones bearing quaternary carbon stereocenters via organocatalytic asymmetric conjugate addition of nitroalkanes to cyclic β-substituted α, β-Enones
CN110467527A (en) A method of preparing trans-D-chrysanthemic acid
CN106478539B (en) A method of preparing chiral dihydro 1,4- benzoxazine compounds
CN101503358B (en) Method for preparing chiral alpha-hydroxy-beta-dicarbonyl compound with lappaconitine as catalyst
CN111116450B (en) Axial chiral naphthylamine squaramide organic catalyst, and preparation method and application thereof
CN114082446A (en) Chiral zirconium catalyst for preparing chiral alpha-hydroxy-beta-keto ester compound and preparation method thereof
CN109824600B (en) Method for synthesizing chiral cyclic urea by palladium-catalyzed asymmetric hydrogenation of 2-hydroxypyrimidine compound
CN109956946B (en) Method for synthesizing chiral amine by asymmetric hydrogenation of dihydropyrrole/indole [1,2-a ] pyrazine under catalysis of iridium

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C02 Deemed withdrawal of patent application after publication (patent law 2001)
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20141210