CN110105212B - Method for preparing beta-hydroxycarbonyl compound - Google Patents

Method for preparing beta-hydroxycarbonyl compound Download PDF

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CN110105212B
CN110105212B CN201910518611.8A CN201910518611A CN110105212B CN 110105212 B CN110105212 B CN 110105212B CN 201910518611 A CN201910518611 A CN 201910518611A CN 110105212 B CN110105212 B CN 110105212B
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aryl
group
cycloalkyl
halogen
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CN110105212A (en
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杨锦明
冯雪馨
吴振
沈志良
邱悦
胡朝俊
杨子健
王庆东
赵玉军
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Nanjing Tech University
Yancheng Teachers University
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Yancheng Teachers University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C221/00—Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
    • 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
    • C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

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Abstract

The present invention relates to a process for the preparation of beta-hydroxycarbonyl compounds, essentially providing a process for the reaction of alpha-halocarbonyl compounds with aldehydes/ketones using inexpensive commercial iron powders to provide the corresponding beta-hydroxycarbonyl compounds. The process has good yield, wide functional group tolerance and good compatibility.

Description

Method for preparing beta-hydroxycarbonyl compound
Technical Field
The invention belongs to the field of chemical medicines, and relates to a method for preparing a beta-hydroxycarbonyl compound, which has good process yield, wide functional group tolerance and good compatibility.
Background
Beta-hydroxy carbonyl compounds are common structural units in a plurality of natural products as important intermediates of organic synthesis, and have wide application in organic chemistry synthesis. Especially fluorine-containing β -hydroxycarbonyl compounds have been shown to possess a variety of biological activities, such as 3- (4-acetylphenyl) -1- ((3R, 5R, 7R) -adamantan-1-yl) -2, 2-difluoro-3-hydroxypropan-1-one, the structure of which is shown below, which, after clinically relevant GABA receptor evaluation, has been determined to be a potent GABA agonist and also presents preliminary in vivo data in alcoholic mice, which compounds tend to reduce the auditory startle response, consistent with anxiolytic characteristics.
Figure BDA0002095861570000011
Organometallic reagents have revolutionized modern organic synthesis, and the past few decades have witnessed the rapid development of organometallic reagents and their widespread use in organic synthesis and material science. Among the various processes for the preparation of the known β -hydroxycarbonyl compounds, the metal-mediated Reformatsky reaction is an efficient and direct process, such as zinc, magnesium or manganese metal-mediated.
Metallic iron is less active than other metals and the use of iron metal in organic synthesis has not attracted much attention, especially in the Reformatsky reaction, but iron is the cheapest, almost least toxic metal in nature.
The present invention provides a reaction of alpha-halocarbonyl compounds with aldehydes/ketones mediated by inexpensive commercial iron powders to provide the corresponding beta-hydroxycarbonyl compounds. The method shows excellent functional group compatibility, and the reaction has very good application prospect in the preparation of medicines, spices or pesticides.
Disclosure of Invention
The invention provides a preparation method of a compound shown in a formula I, which comprises the following steps: in the presence of metallic iron and iodine or FeI2A step of reacting a compound of formula A with a compound of formula B under catalytic conditions to form a compound of formula I,
Figure BDA0002095861570000012
wherein R is1Selected from alkenyl, aryl or heteroaryl, preferably C2-4Alkenyl radical, C6-12Aryl or 5-to 12-membered heteroaryl, said alkenyl, aryl or heteroaryl being optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkyl, alkoxy, nitro, nitrile, alkyl, cycloalkyl, haloalkyl, halocycloalkyl, heterocyclyl, aryl and heteroaryl;
R2selected from hydrogen or alkyl, preferably hydrogen or C1-6An alkyl group optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkyl, alkoxy, nitro, nitrile, alkyl, cycloalkyl, haloalkyl, halocycloalkyl, heterocyclyl, aryl, and heteroaryl;
R3selected from alkyl, OR ' OR NR ' (R '), preferably C1-6Alkyl, OR ', OR NR ' (R "), said alkyl being optionally substituted with one OR more substituents selected from halogen, hydroxy, alkoxy, nitro, nitrile, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein R ' OR R" are independently selected from alkyl, aryl OR heteroaryl, said alkyl, aryl OR heteroaryl being optionally substituted with one OR more substituents selected from halogen, alkyl, cycloalkyl, hydroxy, nitro, nitrile, aryl OR heteroaryl;
Raor RbEach independently selected from hydrogen, halogen, alkyl, cycloalkyl, heterocyclyl, preferably hydrogen, halogen, C1-6Alkyl radical, C3-8Cycloalkyl or 3-to 8-membered heterocyclyl, said alkyl, cycloalkyl or heterocyclyl being optionally substituted by one or more groups selected from alkyl, cycloalkylSubstituted by radicals, heterocyclic radicals, alkoxy radicals, alkenyl radicals, alkynyl radicals, aryl radicals, heteroaryl radicals, nitro radicals, nitrile radicals, hydroxyl radicals, halogens, or RaOr RbTogether with their adjacent carbon atoms form a 3-to 12-membered carbocycle, heterocycle, preferably a 3-to 8-membered carbocycle, heterocycle, which carbocycle or heterocycle is optionally substituted with one or more substituents selected from the group consisting of alkyl, halogen, hydroxy, amino, oxy, carboxy, nitro, cyano, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl;
x is selected from chlorine, bromine and iodine.
In some embodiments, the molar ratio of metallic iron to the compound of formula a is from 1:1 to 5:1, non-limiting examples include 1:1, 1:2, 1:3, 1:4, 1:5, or any value therebetween, preferably 3: 1.
In other embodiments, the solvent used in the reaction of the present invention is selected from aprotic solvents including, but not limited to, at least one of acetonitrile, tetrahydrofuran, toluene, isopropyl ether, methyl tetrahydrofuran, or dichloromethane, preferably acetonitrile.
Further, in a preferred embodiment, the reaction temperature is selected from 30 to 100 ℃, and may be 30 ℃, 40 ℃, 45 ℃, 50 ℃, 55 ℃, 60 ℃, 65 ℃, 70 ℃, 75 ℃, 80 ℃, 85 ℃, 90 ℃, 95 ℃, 100 ℃ or any value between the two, preferably 40 to 80 ℃.
Iodine or FeI on the other hand2The existence of the compound can effectively promote the progress and the yield of the reaction. Further, iodine or FeI in the reaction2In a molar ratio of 0.1:1 to 1:1 with non-limiting examples including 0.1:1, 0.2:1, 0.3:1, 0.4:1, 0.5:1, 0.6:1, 0.7:1, 0.8:1, 0.9:1, 1:1 or any value in between, preferably 0.2:1 to 0.5:1, to the compound of formula a.
In some embodiments, R is as described herein1Selected from vinyl, phenyl, naphthyl, thiazolyl, ferrocenyl, quinolinyl, isoquinolinyl, pyridyl or pyrrolyl, said vinyl, phenyl, naphthyl, thiazolyl, ferrocenyl, quinolinyl, isoquinolinyl, pyridyl or pyrrolyl being optionally substituted by one or more groups selected from halogen, hydroxy, alkyl, alkoxy, nitro, or a pharmaceutically acceptable salt thereof,Nitrile groups, alkyl groups, cycloalkyl groups, haloalkyl groups, halocycloalkyl groups, heterocyclic groups, aryl groups, and heteroaryl groups.
In some embodiments, R is as described herein2Selected from hydrogen, methyl, ethyl or isopropyl.
Further, in some embodiments, R is as described hereinaOr RbEach independently selected from hydrogen, fluoro, methyl or ethyl.
Typical compounds of formula I include, but are not limited to:
Figure BDA0002095861570000031
further, the preparation method of the invention further comprises any step of filtering, washing, concentrating, drying or purifying to obtain a purified target product, namely the compound shown in the formula I.
In another aspect, the invention provides a method for preparing a medicament, a fragrance and a pesticide, comprising the preparation method of the compound shown in the formula I.
Such as, for example,
Figure BDA0002095861570000041
or
Figure BDA0002095861570000042
In another aspect, the invention also provides a process for preparing a compound of formula II,
Figure BDA0002095861570000043
the method comprises the following steps: a step of reacting the compound of the formula II-A with the compound of the formula II-B under the catalysis of metallic iron and iodine,
Figure BDA0002095861570000044
unless stated to the contrary, terms used in the specification and claims have the following meanings.
"alkyl" refers to a saturated aliphatic hydrocarbon group, including straight and branched chain groups of 1 to 20 carbon atoms. Alkyl groups having 1 to 12 carbon atoms are preferred, and alkyl groups having 1 to 6 carbon atoms are more preferred. Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1-dimethylpropyl, 1, 2-dimethylpropyl, 2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, various branched isomers thereof, and the like. Alkyl groups may be substituted or unsubstituted, and when substituted, the substituents may be substituted at any available point of attachment, preferably one or more groups independently selected from aryl, heteroaryl, halo. "alkenyl" includes branched and straight chain olefins having 2 to 12 carbon atoms or olefins containing aliphatic hydrocarbon groups. E.g. "C2-6Alkenyl "denotes alkenyl having 2, 3, 4, 5 or 6 carbon atoms. Examples of alkenyl groups include, but are not limited to, vinyl, allyl, 1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-methylbut-2-enyl, 3-methylbut-1-enyl, 1-pentenyl, 3-pentenyl, and 4-hexenyl.
The term "cycloalkyl" refers to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon substituent, the cycloalkyl ring containing from 3 to 20 carbon atoms, preferably from 3 to 12 carbon atoms, more preferably from 3 to 6 carbon atoms. Non-limiting examples of monocyclic cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl, and the like; polycyclic cycloalkyl groups include spiro, fused and bridged cycloalkyl groups.
The term "heterocyclyl" refers to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon substituent comprising 3 to 20 ring atoms, one or more of which is a heteroatom selected from nitrogen, oxygen, or S (O) m (where m is an integer from 0 to 2), excluding the ring portion of-O-O-, -O-S-, or-S-S-, the remaining ring atoms being carbon. Preferably 3 to 12 ring atoms, of which 1 to 4 are heteroatoms; more preferably from 3 to 6 ring atoms. Non-limiting examples of monocyclic heterocyclyl groups include pyrrolidinyl, imidazolidinyl, tetrahydrofuranyl, tetrahydrothienyl, dihydroimidazolyl, dihydrofuranyl, dihydropyrazolyl, dihydropyrrolyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, homopiperazinyl, and the like.
The term "aryl" refers to a 6 to 14 membered all carbon monocyclic or fused polycyclic (i.e., rings which share adjacent pairs of carbon atoms) group having a conjugated pi-electron system, preferably 6 to 10 membered, such as phenyl and naphthyl.
The aryl group may be substituted or unsubstituted, and when substituted, the substituent is preferably one or more groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, carboxy or carboxylate, preferably phenyl.
The term "heteroaryl" refers to a heteroaromatic system comprising 1 to 4 heteroatoms, 5 to 14 ring atoms, wherein the heteroatoms are selected from oxygen, sulfur and nitrogen. Heteroaryl is preferably 5 to 12 membered, such as imidazolyl, furyl, thienyl, thiazolyl, pyrazolyl, oxazolyl, pyrrolyl, tetrazolyl, pyridyl, pyrimidinyl, thiadiazole, pyrazinyl and the like, preferably imidazolyl, pyrazolyl, pyrimidinyl or thiazolyl. Heteroaryl groups may be optionally substituted or unsubstituted.
The term "alkoxy" refers to-O- (alkyl) and-O- (unsubstituted cycloalkyl), wherein alkyl is as defined above. Non-limiting examples of alkoxy groups include: methoxy, ethoxy, propoxy, butoxy, cyclopropoxy, cyclobutoxy, cyclopentyloxy, cyclohexyloxy. Alkoxy groups may be optionally substituted or unsubstituted, and when substituted, the substituents are preferably one or more groups independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxy, nitro, cyano, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, carboxy or carboxylate groups.
The term "haloalkyl" refers to an alkyl group substituted with a halogen, wherein alkyl is as defined above.
The term "halocycloalkyl" refers to a cyclic group substituted with a halogen, wherein cycloalkyl is as defined above.
The term "hydroxy" refers to an-OH group.
The term "halogen" refers to fluorine, chlorine, bromine or iodine.
The term "cyano" refers to — CN.
The term "nitro" means-NO2。
"optional" or "optionally" means that the subsequently described event or circumstance may, but need not, occur, and that the description includes instances where the event or circumstance occurs or does not. For example, "a heterocyclic group optionally substituted with an alkyl" means that an alkyl may, but need not, be present, and the description includes the case where the heterocyclic group is substituted with an alkyl and the heterocyclic group is not substituted with an alkyl.
"substituted" means that one or more, preferably up to 5, more preferably 1 to 3, hydrogen atoms in the group are independently substituted with a corresponding number of substituents. It goes without saying that the substituents are only in their possible chemical positions, and that the person skilled in the art is able to determine (experimentally or theoretically) possible or impossible substitutions without undue effort. For example, amino or hydroxyl groups having free hydrogen may be unstable in combination with carbon atoms having unsaturated (e.g., olefinic) bonds.
Detailed Description
The present invention will be explained in detail with reference to specific examples below, so that those skilled in the art can more fully understand the specific examples of the present invention to illustrate the technical solutions of the present invention, and not to limit the present invention in any way.
Example 1:
Figure BDA0002095861570000061
adding 4-chlorobenzaldehyde (1mmol), alpha-bromoethyl acetate (3mmol), iron powder (168mg, 3mmol), acetonitrile (2ml) and catalyst 2 into a 10ml reaction bottle, heating to 60 ℃, stirring for reaction for 24 hours, adding 20ml ammonium chloride solution, extracting with ethyl acetate, washing with saline, drying, filtering, concentrating to obtain a compound 3a, passing through 1, 4-dimethoxybenzene as an internal standard substance,1HNMR detected the amount of compound 3a and calculated the yield, and the data are shown in the following table:
Figure BDA0002095861570000071
note: silica gel column chromatography yield
Compound 3 a: colorless oil;
1HNMR(400MHz,CDCl3):δ7.63(d,J＝8.3Hz,2H),7.48(d,J＝8.2Hz,2H),5.16(t,J＝6.0Hz,1H),4.16(q,J＝7.1Hz,2H),3.72(s,1H),2.69-2.67(m,2H),1.24(t,J＝7.1Hz,3H)ppm.
13C NMR(100MHz,CDCl3):δ172.2,141.5,131.5,127.4,121.5,69.6,61.0,43.1,14.1ppm.
example 2
Figure BDA0002095861570000072
Adding 4-chlorobenzaldehyde (1mmol), alpha-bromoethyl acetate (3mmol), iron powder (168mg, 3mmol), iodine (0.2mmol) and solvent into a 10ml reaction bottle, heating to 60 ℃, stirring for reaction for 24 hours, adding 20ml ammonium chloride solution, extracting with ethyl acetate, washing with saline, drying, filtering, concentrating to obtain a compound 3a, passing through 1, 4-dimethoxybenzene as an internal standard substance,1HNMR detected the amount of compound 3a and calculated the yield, and the data are shown in the following table:
Figure BDA0002095861570000073
note: silica gel column chromatography yield
Example 3
Figure BDA0002095861570000081
Respectively adding aldehyde compounds 1b-n (1mmol), alpha-bromoethyl acetate (3mmol), iron powder (168mg, 3mmol), iodine (0.2mmol) and a solvent (2ml) into a 10ml reaction bottle, heating to 60 ℃, stirring to react completely, adding 20ml ammonium chloride solution, extracting with ethyl acetate, washing with brine, drying, filtering, concentrating, purifying with a silica gel chromatographic column to obtain target products 3b-n, and respectively calculating the yield, wherein the specific data are as follows:
Figure BDA0002095861570000082
note: the solvent is tetrahydrofuran
Example 4
Figure BDA0002095861570000091
Respectively adding the compounds 2b-g (3mmol) and 4-chlorobenzaldehyde (1mmol), iron powder (168mg, 3mmol), iodine (0.2mmol) and acetonitrile (2ml) into a 10ml reaction bottle, heating to 60 ℃, stirring to react completely, adding 20ml ammonium chloride solution, extracting with ethyl acetate, washing with saline, drying, filtering, concentrating, purifying by a silica gel chromatographic column to obtain the target products 4b-g, and respectively calculating the yield, wherein the specific data are as follows:
Figure BDA0002095861570000092
example 5
Figure BDA0002095861570000093
Adding the compounds 5b-h (1mmol), alpha-bromoethyl acetate (3mmol), iron powder (168mg, 3mmol), iodine (0.2mmol) and acetonitrile (2ml) into a 10ml reaction bottle, heating to 60 ℃, stirring to react completely, adding 20ml ammonium chloride solution, extracting with ethyl acetate, washing with brine, drying, filtering, concentrating, purifying with a silica gel chromatographic column to obtain the target products 5b-h, and respectively calculating the yield, wherein the specific data are as follows:
Figure BDA0002095861570000094
Figure BDA0002095861570000101

Claims (13)

1. a process for preparing a compound of formula I,
Figure FDA0003255525300000011
the method comprises the following steps: in the presence of metallic iron and iodine or metallic iron and FeI2A step of reacting a compound of formula A with a compound of formula B under catalytic conditions to form a compound of formula I,
Figure FDA0003255525300000012
wherein R is1Selected from alkenyl, aryl or heteroaryl, said alkenyl, aryl or heteroaryl being optionally substituted by one or more substituents selected from halogen, hydroxy, alkyl, alkoxy, nitro, nitrile, alkyl, cycloalkyl, haloalkyl, halocycloalkyl, heterocyclyl and aryl;
R2selected from hydrogen or alkyl, said alkyl being optionally substituted by one or more substituents selected from halogen, hydroxy, alkyl, alkoxy, nitro, nitrile, alkyl, cycloalkyl, haloalkyl, halocycloalkyl, heterocyclyl and aryl;
R3selected from alkyl, OR ' OR NR ' (R '), said alkyl being optionally substitutedSubstituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkoxy, nitro, nitrile, cycloalkyl, heterocyclyl and aryl, wherein R' or R "is independently selected from alkyl, aryl or heteroaryl, said alkyl, aryl or heteroaryl being optionally substituted with one or more substituents selected from the group consisting of halogen, alkyl, cycloalkyl, hydroxy, nitro, nitrile, aryl or heteroaryl;
Raor RbEach independently selected from hydrogen, halogen, alkyl, cycloalkyl, heterocyclyl, said alkyl, cycloalkyl or heterocyclyl being optionally substituted by one or more groups selected from alkyl, cycloalkyl, heterocyclyl, alkoxy, alkenyl, alkynyl, aryl, nitro, nitrile, hydroxy, halogen, or RaOr RbTogether with their adjacent carbon atoms form a 3-to 12-membered carbocyclic ring, heterocyclic ring, which carbocyclic or heterocyclic ring is optionally substituted with one or more substituents selected from alkyl, halogen, hydroxy, amino, oxy, carboxy, nitro, cyano, alkoxy, cycloalkyl, heterocyclyl and aryl;
x is selected from chlorine, bromine and iodine.
2. The method of claim 1, wherein R1Is selected from C2-4Alkenyl radical, C6-12Aryl or 5-to 12-membered heteroaryl, said alkenyl, aryl or heteroaryl optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxy, alkyl, alkoxy, nitro, nitrile, alkyl, cycloalkyl, haloalkyl, halocycloalkyl, heterocyclyl and aryl;
R2selected from hydrogen or C1-6An alkyl group optionally substituted with one or more substituents selected from the group consisting of halogen, hydroxyl, alkyl, alkoxy, nitro, nitrile, alkyl, cycloalkyl, haloalkyl, halocycloalkyl, heterocyclyl, and aryl;
R3is selected from C1-6Alkyl, OR ', OR NR' (R "), the alkyl being optionally substituted with one OR more substituents selected from halogen, hydroxy, alkoxy, nitro, nitrile, cycloalkyl, heterocyclyl and aryl, wherein R 'OR R" is independently selected from alkyl, aryl OR heteroaryl, the alkyl, aryl OR NR' (R ″) groups being optionally substituted with one OR more substituents selected from halogen, hydroxy, alkoxy, nitro, nitrile, cycloalkyl, heterocyclyl and aryl groupsHeteroaryl is optionally substituted with one or more groups selected from halogen, alkyl, cycloalkyl, hydroxy, nitro, nitrile, aryl or heteroaryl;
Raor RbEach independently selected from hydrogen, halogen, C1-6Alkyl radical, C3-8Cycloalkyl or 3-to 8-membered heterocyclyl, said alkyl, cycloalkyl or heterocyclyl being optionally substituted with one or more groups selected from alkyl, cycloalkyl, heterocyclyl, alkoxy, alkenyl, alkynyl, aryl, nitro, nitrile, hydroxy, halogen, or, RaOr RbTogether with their adjacent carbon atoms form a 3-to 8-membered carbocyclic, heterocyclic ring, which carbocyclic or heterocyclic ring is optionally substituted with one or more substituents selected from alkyl, halogen, hydroxy, amino, oxy, carboxy, nitro, cyano, alkoxy, cycloalkyl, heterocyclyl and aryl.
3. The method of claim 1 or 2, wherein the molar ratio of the metallic iron to the compound of formula a is 1:1 to 5: 1.
4. The method of claim 1 or 2, wherein the iodine or FeI2The molar ratio of the amount of the compound (B) to the compound (A) is 0.1: 1-1: 1.
5. The method of claim 4, wherein the iodine or FeI2The molar ratio of the amount of the compound (B) to the compound (A) is 0.2: 1-0.5: 1.
6. The process as claimed in claim 1, wherein the solvent used for the reaction is selected from aprotic solvents.
7. The process according to claim 6, wherein the solvent used for the reaction is at least one selected from acetonitrile, tetrahydrofuran, toluene, isopropyl ether, methyltetrahydrofuran or dichloromethane.
8. The method of claim 1 or 2, wherein R1Selected from vinyl, phenyl, naphthyl, thiazolyl, ferrocenyl, quinolyl and isoquinolineA vinyl group, a phenyl group, a naphthyl group, a thiazolyl group, a ferrocenyl group, a quinolyl group, an isoquinolyl group, a pyridyl group, or a pyrrolyl group, the vinyl group, the phenyl group, the naphthyl group, the thiazolyl group, the ferrocenyl group, the quinolyl group, the isoquinolyl group, the pyridyl group, or the pyrrolyl group being optionally substituted with one or more groups selected from the group consisting of halogen, hydroxyl, alkyl, alkoxy, nitro, nitrile, alkyl, cycloalkyl, haloalkyl, halocycloalkyl, heterocyclyl, and aryl.
9. The method of claim 1 or 2, wherein R2Selected from hydrogen, methyl, ethyl or isopropyl.
10. The method of claim 1 or 2, wherein R3Is selected from OCH3、OC2H5、NMe2Or OBn.
11. The method of claim 1 or 2, wherein RaOr RbEach independently selected from hydrogen, fluoro, methyl or ethyl.
12. A process for the preparation of a medicament, fragrance or pesticide, comprising a process for the preparation of a compound of formula I according to any one of claims 1 to 11.
13. A process for the preparation of a compound of formula II,
Figure FDA0003255525300000031
the method comprises the following steps: a step of reacting the compound of the formula II-A with the compound of the formula II-B under the catalysis of metallic iron and iodine,
Figure FDA0003255525300000032
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