CN108299486B - Method for preparing cyclopropyl borate compound based on iron catalysis - Google Patents

Method for preparing cyclopropyl borate compound based on iron catalysis Download PDF

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CN108299486B
CN108299486B CN201810235802.9A CN201810235802A CN108299486B CN 108299486 B CN108299486 B CN 108299486B CN 201810235802 A CN201810235802 A CN 201810235802A CN 108299486 B CN108299486 B CN 108299486B
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周宇涵
曲景平
柳阳
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Dalian University of Technology
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Abstract

The invention relates to a method for preparing a cyclopropyl borate compound based on iron catalysis, and belongs to the field of compound preparation. A method for preparing cyclopropyl borate compound based on iron catalysis comprises the steps of reacting a compound shown as a general formula II and pinacol diboron ester serving as raw materials in a solvent in the presence of ferric salt and alkali according to the following reaction formula to obtain a compound shown as a general formula I,

Description

Method for preparing cyclopropyl borate compound based on iron catalysis
Technical Field
The invention relates to a method for preparing a cyclopropyl borate compound based on iron catalysis, and belongs to the field of compound preparation.
Background
Cyclopropyl has a large ring tension and, due to its unique structural and electronic properties, tends to exhibit surprising properties in participating in the reaction. In addition, many compounds containing cyclopropane groups exhibit excellent biological activities in medicine and pesticide, such as enzyme inhibitors, herbicides, antibacterial agents, antiviral agents, and the like (chem.soc.rev.2012,41,4631.Tetrahedron 2001,57,8589.), as shown in fig. 1.
Alkyl borate esters and alkyl boronic acids are a very important intermediate in the field of Organic Synthesis (Boronic acids: Preparation and Applications in Organic Synthesis and Medicine, Wiley-VCH, Weinheim,2005), and have been widely used in the Synthesis of various drugs and functional material molecules. Compounds containing a boronic acid ester functionality, in addition to being useful in classical Suzuki-Miyaura coupling reactions (angelw. chem. int. ed.2011,50,6722.), can be more readily derivatized to convert the functionality to the corresponding alcohol, aldehyde, amine functionality (chem. commu.2013, 49,11230.). Most of the compounds containing borate or borate functional groups have good stability compared with other metal organic nucleophiles (such as a Grignard reagent, a lithium reagent and a zinc reagent), and can be directly purified and stored in an air atmosphere, so that the synthesis of the borate compounds with diversified functional groups has great significance.
Cyclopropyl borate ester having a cyclopropyl functional group and a borate functional group introduced into the same molecule is an excellent organic synthetic block, and its synthetic method is mainly divided into the following four methods, first, hydroboration reaction of a substrate containing cyclopropene (j.am.chem.soc.2003,125, 7198.); second, carbon-hydrogen bond, carbon-halogen bond activation boronation with cyclopropyl (acscatal.2016,6,8332.); thirdly, performing secondary filtration; cyclopropanation of an alkenyl borate substrate (adv. synth. catl. 2002,344, 1063); fourthly, boronation/cyclization of double bonds containing allyl carbonate, phosphate ester, etc. synthesizes cyclopropyl borate ester (angelw.chem.int.ed.2008, 47,7424.j.am.chem.soc.2010,132, 11440.). The Ito topic group can synthesize a cyclopropyl borate compound with high regio-stereoselectivity by copper-catalyzing 3-substituted allyl carbonates and allyl phosphonates. However, the synthesis of cyclopropyl boronic acid esters by iron catalyzed allyl carbonate has not been reported.
Disclosure of Invention
The invention aims to provide a method for efficiently, simply and economically synthesizing cyclopropyl borate compounds (compounds shown in a general formula I) by using cheap and commercially available iron salts as catalysts, pinacol diborate as a boronizing reagent and aryl allyl esters (compounds shown in a general formula II) as raw materials.
A method for preparing cyclopropyl borate compound based on iron catalysis comprises the steps of reacting a compound shown as a general formula II and a pinacol diboron ester serving as raw materials in the presence of iron salt and alkali according to the following reaction formula to obtain a compound shown as a general formula I,
Figure GDA0001653203140000021
wherein the content of the first and second substances,
R1is selected from
Figure GDA0001653203140000022
Wherein n is 1-5;
R2is selected from R4OCOO-、(EtO)2POO-、MeCOO-；
R3Selected from H, C1-C6 alkyl, phenyl, halogen, trifluoromethyl, trifluoromethoxy, phenoxy, acetyl, C1-C4 alkoxy;
R4selected from C1-C4 alkyl;
the ferric salt is at least 1 selected from ferrous chloride, ferric chloride, ferrous bromide, ferric acetylacetonate, ferrous acetate and ferrous trifluoromethanesulfonate;
the alkali is selected from at least 1 of potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, sodium methoxide, lithium methoxide and potassium methoxide;
the solvent is at least 1 selected from tetrahydrofuran, methyl tert-butyl ether, 1, 4-dioxane, n-butyl ether, isopropyl ether, dimethyl sulfoxide and toluene.
The solvent of the invention can be used in an amount meeting the reaction requirement, and the preferable amount ratio of the compound shown in the general formula II to the solvent is 1mmol: 20-50 mL.
Unless otherwise indicated, the terms used herein have the following meanings.
The term "alkyl" as used herein includes straight chain and branched chain alkyl groups. Reference to a single alkyl group, such as "propyl", is intended to refer only to straight chain alkyl groups, and reference to a single branched alkyl group, such as "isopropyl", is intended to refer only to branched alkyl groups. For example, "C4 lower alkyl" includes methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, and the like. Similar rules apply to other groups used in this specification.
The term "halogen" as used herein includes fluorine, chlorine, bromine, iodine.
The C1-C4 alkoxy group is a group having the following structure: -O-M1Wherein M is1Is C1-C4 alkyl, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy.
In the above technical solution, the
Figure GDA0001653203140000041
(n is 1 to 5), wherein (R)3)nWherein n is 1 to 5R3The substitution on the phenyl group may be mono-or poly-substituted and may be 1,2, 3,4 or 5. When n is 1, the substituent is monosubstituted, and the monosubstituted substituent can be 2,3 or 4; when n is 2,3,4 or 5,is a polysubstitution, wherein n ═ 2 is disubstituted, and the disubstituted position is 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, 3, 5-; n-3 is trisubstituted with the trisubstituted substitution positions being 2,3,4-, 2,3,5-, 2,3,6-, 3,4, 5-.
R2Is selected from R4OCOO-、(EtO)2POO-, MeCOO-, further, R2Is t-BuOCOO-, MeOOCOO-, (EtO)2POO-、MeCOO-。
R3Selected from H, C1-C6 alkyl, phenyl, halogen, trifluoromethyl, trifluoromethoxy, phenoxy, acetyl, C1-C4 alkoxy; further, R3Is H, methyl, methoxy, halogen, isopropyl, trifluoromethoxy, phenyl, phenoxy, acetyl.
The amount of the alkali substance is 0.6-2 times of that of the compound substance shown in the general formula II.
The amount of the matter of the diboron pinacol ester is 1-2 times of that of the compound shown in the general formula II.
The amount of the ferric salt catalyst is 1-10%, preferably 5-10% of the amount of the compound shown in the general formula II.
The reaction temperature is 25-solvent reflux temperature, and the reaction time is 7-48 h, preferably 18-48 h. Different solvents have different reflux temperatures, such as: tetrahydrofuran 66 ℃, methyl tert-butyl ether 55 ℃,1, 4-dioxane 101 ℃, n-butyl ether 142 ℃, isopropyl ether 68 ℃, dimethyl sulfoxide 189 ℃ and toluene 110 ℃.
The amount of the ligand substance is 10-20% of the amount of the compound substance shown in the general formula II.
A preferred technical scheme of the invention is as follows:
a method for preparing cyclopropyl borate compound based on iron catalysis is characterized in that a compound shown in a general formula II and pinacol biborate ester are used as raw materials in a solvent, and a ligand is added or not added in the presence of iron salt and alkali. Carrying out reaction according to the following reaction formula to obtain a compound shown as a general formula I, wherein the reaction temperature is 25-solvent reflux temperature, and the reaction time is 7-48 h;
Figure GDA0001653203140000051
wherein the content of the first and second substances,
R1is selected from
Figure GDA0001653203140000052
Wherein n is 1-5;
R2is selected from R4OCOO-、(EtO)2POO-、MeCOO-；
R3Selected from H, C1-C6 alkyl, phenyl, halogen, trifluoromethyl, trifluoromethoxy, phenoxy, acetyl, C1-C4 alkoxy;
R4selected from C1-C4 alkyl;
the ferric salt is at least 1 of ferrous chloride, ferric chloride, ferrous bromide, ferric acetylacetonate, ferrous acetate and ferrous trifluoromethanesulfonate;
the alkali is selected from at least 1 of potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, sodium methoxide, lithium methoxide and potassium methoxide;
the ligand is selected from triphenylphosphine, tri-n-butylphosphine, 4, 5-bis (diphenylphosphine) -9, 9-dimethylxanthene, 4-dimethylaminopyridine, 1, 2-bis (diphenylphosphine) ethane, 1, 2-bis (diphenylphosphine) propane, triethyl phosphite and tetramethylethylenediamine;
the solvent is at least 1 selected from tetrahydrofuran, methyl tert-butyl ether, 1, 4-dioxane, n-butyl ether, isopropyl ether, dimethyl sulfoxide and toluene.
Specific structures of substituents of the respective raw material compounds in the above reaction formulae are listed in table 1.
TABLE 1
Figure GDA0001653203140000061
Figure GDA0001653203140000071
Figure GDA0001653203140000081
Figure GDA0001653203140000091
Figure GDA0001653203140000101
Figure GDA0001653203140000111
The product obtained by the method is raceme, and trans configuration is mainly trans configuration. Table 2 lists the structures, isomer ratios, physical properties and major isomers (trans) of specific compounds 1 to 18 synthesized by the present invention1HNMR data, but the present invention is not limited to these compounds.
TABLE 2
Figure GDA0001653203140000112
Figure GDA0001653203140000121
Figure GDA0001653203140000131
Determination of cis-trans configuration of the product: in 2010, the Hajime Ito project group (J.am. chem. Soc.2010,132,11440) achieved copper-catalyzed enantioselective control of cyclopropyl boronation of allyl phosphonates. Further, the cis-trans configuration of aryl group and borate ester on cyclopropane can be clarified by NOE (Nuclear Overhauser Effect). For compound 1 as an example, the hydrogen nuclear magnetic data for the trans configurational isomer is:1H NMR(300MHz,CDCl3):δ7.21-7.28(m,2H),7.05-7.17(m,3H),2.10(dt,J＝8.1,5.4Hz,1H),1.25(s,6H),1.24(s,6H),1.16(ddd,J＝8.1,6.8,3.6Hz,1H),1.00(ddd,J＝9.8,5.4,3.7Hz,1H),0.30(ddd, J ═ 9.8,6.8,5.4Hz, 1H). And the hydrogen nuclear magnetic data of cis configurational isomers are:1H NMR(300MHz,CDCl3) δ 7.18-7.31(m,4H),7.08-7.16(m,1H),2.35(ddd, J ═ 10.1,7.8,6.1Hz,1H),1.28(ddd, J ═ 7.1,6.1,4.2Hz,1H),1.10(ddd, J ═ 9.3,8.0,4.2Hz,1H),1.01(s,6H),0.88(s,6H),0.44(ddd, J ═ 10.1,9.3,7.3Hz, 1H). By comparing the above data, it can be seen that the main configuration of the product obtained by the present invention is trans.
The invention has the beneficial effects that: the iron is used as a second-highest metal element in the earth crust and an indispensable trace element in the human body, has the advantages of rich content, low price, easy obtaining, low toxicity and environmental friendliness, and meets the requirements of current sustainable development and green chemistry by developing a catalyst on the basis of the iron. The method uses cheap and commercially available metal iron salt as a catalyst, and provides a convenient and low-cost method for preparing the cyclopropyl borate.
Drawings
FIG. 1 is a drug containing cyclopropane groups and a natural product with biological activity.
Detailed Description
The following non-limiting examples are presented to enable those of ordinary skill in the art to more fully understand the present invention and are not intended to limit the invention in any way.
The test methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials are commercially available, unless otherwise specified.
Example 1
2' -Phenylcyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 1)
To a 50mL dry Schlenk flask under argon atmosphere at room temperature were added ferric chloride (8.1mg,0.05mmol), THF20mL, pinacol diborate (190mg,0.75mmol), potassium tert-butoxide (62mg,0.55mmol) and 1, 3-bis (diphenylphosphino) propane (21mg,0.05mmol) in that order, stirred at room temperature for 1h, followed by the addition of cinnamyl tert-butylcarbonate substrate (0.5mmol), blocked and allowed to react at 65 ℃ for 30 h. After the reaction is finished, the temperature is reduced to room temperature, the sulfur powder is added under the protection of argon, and the mixture is stirred for 1 hour at room temperature. By rotary steamingThe solvent was removed, saturated brine (20mL) was added, extraction was performed 3 times with ethyl acetate, the combined organic phases were washed with saturated brine (2X 10mL) and then with anhydrous Na2SO4Drying, and performing column chromatography to obtain the target compound, wherein the filling material is silica gel, the eluent is petroleum ether and ethyl acetate (100:1-100:3), and the separation yield is 87%.
Example 2
2' - (4 "-fluorophenyl) cyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 2)
The procedure was carried out in the same manner as in example 1 except for replacing cinnamyl tert-butyl carbonate with 4-fluorocinnamyl tert-butyl carbonate in the same molar amount as that of cinnamyl tert-butyl carbonate in example 1, thereby obtaining an isolation yield of the objective compound of 95%.
Example 3
2' - (4 "-chlorophenyl) cyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 3)
The same procedure as in example 1 was repeated except for replacing cinnamyl tert-butyl carbonate with 4-chlorocinnamyl tert-butyl carbonate in the same molar amount as that of cinnamyl tert-butyl carbonate in example 1, to obtain an isolated yield of the desired compound of 74%.
Example 4
2' - (4 "-bromophenyl) cyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 4)
Except for replacing the tert-butyl cinnamyl carbonate in example 1 with tert-butyl 4-bromocinnamyl carbonate with the same molar amount, the amount of potassium tert-butoxide is reduced to 0.9 times equivalent, and the reaction time is shortened to 24 h. The procedure was carried out in the same manner as in example 1 to obtain an isolated yield of the objective compound of 65%.
Example 5
2' - (4 "-methylphenyl) cyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 5)
The procedure was carried out in the same manner as in example 1 except for replacing cinnamyl tert-butyl carbonate with 4-methyl cinnamyl tert-butyl carbonate in the same molar amount as that of the cinnamyl tert-butyl carbonate in example 1, thereby obtaining an isolated yield of the objective compound of 93%.
Example 6
2' - (4 "-methoxyphenyl) cyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 6)
Except for replacing the tert-butyl cinnamyl carbonate in example 1 with tert-butyl 4-methoxy cinnamyl carbonate with the same molar amount, the amount of potassium tert-butoxide is increased to 1.2 times equivalent, and the reaction time is shortened to 40 h. The procedure was carried out in the same manner as in example 1 to obtain an isolated yield of the objective compound of 86%.
Example 7
2' - (4 "-trifluoromethoxyphenyl) cyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 7)
Except for replacing the tert-butyl cinnamyl carbonate in example 1 with tert-butyl 4-trifluoromethoxy cinnamyl carbonate with the same molar amount, the amount of potassium tert-butoxide was increased to 1.2 times the equivalent, and the reaction time was shortened to 40 h. The procedure was carried out in the same manner as in example 1 to obtain an isolated yield of the objective compound of 70%.
Example 8
2' - (4 "-phenoxyphenyl) cyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 8)
Except for replacing the cinnamyl tert-butyl carbonate in example 1 with 4-phenoxycinnamyl tert-butyl carbonate with the same molar amount, the amount of potassium tert-butoxide is increased to 1.2 times equivalent, and the reaction time is shortened to 40 h. The procedure was carried out in the same manner as in example 1 to obtain an isolated yield of the objective compound of 92%.
Example 9
2' - (2 "-methylphenyl) cyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (compound 9)
The procedure was carried out in the same manner as in example 1 except for replacing cinnamyl tert-butyl carbonate with 2-methyl cinnamyl tert-butyl carbonate in the same molar amount as that of the cinnamyl tert-butyl carbonate in example 1, thereby obtaining an isolated yield of the objective compound of 75%.
Example 10
2' - (3 "-methylphenyl) cyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (compound 10)
The procedure was carried out in the same manner as in example 1 except for replacing cinnamyl tert-butyl carbonate with 3-methyl cinnamyl tert-butyl carbonate in the same molar amount as that of cinnamyl tert-butyl carbonate in example 1, thereby obtaining an isolated yield of the objective compound of 64%.
Example 11
2 ' - (3 ', 5 ' -dimethylphenyl) cyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (compound 11)
The same procedure as in example 1 was repeated except for replacing cinnamyl tert-butyl carbonate in example 1 with 3, 5-dimethylcinnamyl tert-butyl carbonate in the same molar amount, thereby obtaining an isolated yield of the desired compound of 74%.
Example 12
2' - (4 "-fluoro-3" -methylphenyl) cyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 12)
Except for replacing the cinnamyl tert-butyl carbonate in example 1 with the same molar amount of 4-fluoro-3-methyl cinnamyl tert-butyl carbonate, the amount of potassium tert-butoxide was increased to 1.2 times the equivalent, and the reaction time was shortened to 40 h. The procedure was carried out in the same manner as in example 1 to obtain an isolated yield of the objective compound of 85%.
Example 13
2 '- (3', 4 ', 5' -trimethoxyphenyl) cyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (compound 13)
Except for replacing the tert-butyl cinnamyl carbonate in example 1 with the same molar amount of tert-butyl 3,4, 5-trimethoxy cinnamyl carbonate, the amount of potassium tert-butoxide is increased to 1.2 times equivalent, and the reaction time is shortened to 40 h. The procedure was carried out in the same manner as in example 1 to obtain an isolated yield of the objective compound of 90%.
Example 14
2' - (4 "-acetylphenyl) cyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (compound 14)
The procedure of example 1 was repeated in the same manner as in example 1 except that cinnamyl tert-butyl carbonate in example 1 was replaced with 4- (2 '-methyl-1', 3 '-dioxan-2' -yl) cinnamyl tert-butyl carbonate in the same molar amount, and the crude product was hydrolyzed with dilute hydrochloric acid at room temperature for half an hour and then separated and purified correspondingly to obtain the desired compound in an isolated yield of 88%.
Example 15
2' - (4 "-isopropylphenyl) cyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 15)
The procedure was carried out in the same manner as in example 1 except for replacing cinnamyl tert-butyl carbonate with 4-isopropyl cinnamyl tert-butyl carbonate in the same molar amount as that of example 1 to obtain an isolated yield of the objective compound of 79%.
Example 16
2 ' - (2 ', 5 ' -difluorophenyl) cyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborono) cyclopentane (compound 16)
The procedure of example 1 was repeated in the same manner except that the t-butylcinnamyl carbonate in example 1 was changed to the same molar amount of 2, 5-difluorocinnamyl carbonate, to obtain the target compound with a hydrogen nuclear magnetic yield of 50% (using 1,1,2, 2-tetrachloroethane as an internal standard), and the target compound was subjected to reverse-phase preparative chromatography (C18 column, eluent methanol/water 70:30 to 100: 0).
Example 17
2' - (1 "-naphthyl) cyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (compound 17)
The procedure of example 1 was repeated in the same manner as in example 1 except that cinnamyl tert-butyl carbonate in example 1 was replaced with 3- (1' -naphthyl) propenyl tert-butyl carbonate in the same molar amount, to obtain the target compound with a hydrogen nuclear magnetic yield of 70% (using 1,1,2, 2-tetrachloroethane as an internal standard), and the target compound was subjected to reverse phase preparative chromatography (C18 column, eluent methanol/water ═ 70:30 to 100: 0).
Example 18
2' - (4 "-phenylphenyl) cyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 18)
The procedure of example 1 was repeated in the same manner except that the tert-butyl cinnamyl carbonate in example 1 was changed to tert-butyl-4-phenylcinnamyl carbonate in the same molar amount, thereby obtaining a target compound with a hydrogen nuclear magnetic yield of 60% (using 1,1,2, 2-tetrachloroethane as an internal standard) and subjecting the target compound to reverse phase preparative chromatography (C18 column, eluent methanol/water 70:30 to 100: 0).
Example 19
2' -Phenylcyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 1)
To a 25mL dry Schlenk flask under argon atmosphere at room temperature were added sequentially ferrous triflate (10.6mg,0.03mmol), THF10mL, pinacol diboron diborate (114mg,0.45mmol), potassium tert-butoxide (34mg,0.3mmol), followed by the addition of the cinnamyl tert-butylcarbonate substrate (0.3mmol), blocking and reaction at 65 ℃ for 7 h. After completion of the reaction, the temperature was lowered to room temperature, the solvent was removed by a rotary evaporator, a saturated brine (20mL) was added, extraction was performed with ethyl acetate 3 times, the combined organic phases were washed with a saturated brine (2X 10mL) and then with anhydrous Na2SO4Drying to obtain the target compound with 61% of hydrogen nuclear magnetic yield (1, 1,2, 2-tetrachloroethane is taken as an internal standard).
Example 20
2' -Phenylcyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 1)
The procedure was carried out in the same manner as in example 19 except for replacing iron trifluoromethanesulfonate with an equimolar amount of ferric chloride and replacing cinnamyl tert-butyl carbonate with an equimolar amount of cinnamyl diethylphosphonate in example 19 to obtain a hydrogen nuclear magnetic yield of the target compound of 41% (using 1,1,2, 2-tetrachloroethane as an internal standard).
Example 21
2' -Phenylcyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 1)
The procedure was carried out in the same manner as in example 19 except for replacing iron trifluoromethanesulfonate with the same molar amount of iron chloride and replacing potassium tert-butoxide with the same molar amount of sodium tert-butoxide as in example 19, thereby obtaining a hydrogen nuclear magnetic yield of the objective compound of 68% (using 1,1,2, 2-tetrachloroethane as an internal standard).
Example 22
2' -Phenylcyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 1)
The same procedures used in example 19 were repeated except for changing the ferrous trifluoromethanesulfonate to ferric chloride in the same molar amount and changing the solvent tetrahydrofuran to n-butyl ether used in example 19 to obtain a hydrogen nuclear magnetic yield of 62% of the objective compound (using 1,1,2, 2-tetrachloroethane as an internal standard).
Example 23
2' -Phenylcyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 1)
The same procedure as in example 19 was repeated except that ferrous triflate was replaced with the same molar amount of ferric chloride in example 19 and the reaction temperature was lowered to 65 ℃ to room temperature, to obtain a hydrogen nuclear magnetic yield of the objective compound of 8% (using 1,1,2, 2-tetrachloroethane as an internal standard).
Example 24
2' -Phenylcyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 1)
To a 25mL dry Schlenk flask under argon atmosphere at room temperature were added ferric chloride (4.9mg,0.03mmol), THF10mL, pinacol diborate (114mg,0.45mmol), potassium tert-butoxide (34mg,0.3mmol) and 1, 3-bis (diphenylphosphino) propane (12.4mg,0.03mmol) in that order, followed by the addition of the cinnamyl tert-butylcarbonate substrate (0.3mmol), blocking and reacting at 65 ℃ for 18 h. After completion of the reaction, the temperature was lowered to room temperature, the solvent was removed by a rotary evaporator, a saturated brine (20mL) was added, extraction was performed with ethyl acetate 3 times, the combined organic phases were washed with a saturated brine (2X 10mL) and then with anhydrous Na2SO4Drying to obtain the target compound with 82% of hydrogen nuclear magnetic yield (taking 1,1,2, 2-tetrachloroethane as an internal standard).
Example 25
2' -Phenylcyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 1)
The procedure was carried out in the same manner as in example 24 except for replacing the ligand 1, 3-bis (diphenylphosphino) propane in example 24 with an equimolar amount of tetramethylethylenediamine, to obtain a hydrogen nuclear magnetic yield of the objective compound of 80% (using 1,1,2, 2-tetrachloroethane as an internal standard).
Example 26
2' -Phenylcyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 1)
The reaction time was extended to 24h, except that the amount of the ligand 1, 3-bis (diphenylphosphino) propane used in example 24 was increased to 0.06 mmol. The procedure was carried out in the same manner as in example 24 to obtain a hydrogen nuclear magnetic yield of 76% of the objective compound (using 1,1,2, 2-tetrachloroethane as an internal standard).
Example 27
2' -Phenylcyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 1)
The reaction time was prolonged to 24 hours, except that the amount of potassium t-butoxide used in example 24 was reduced to 0.6 equivalent. The procedure was carried out in the same manner as in example 24 to obtain a 77% nuclear magnetic yield of hydrogen as a target compound (using 1,1,2, 2-tetrachloroethane as an internal standard).
Example 28
2' -Phenylcyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 1)
To a 25mL dry Schlenk flask under argon atmosphere at room temperature were added ferric chloride (4.9mg,0.03mmol), THF10mL, pinacol diboron diborate (114mg,0.45mmol), potassium tert-butoxide (34mg,0.3mmol) in that order, followed by the addition of the cinnamyl tert-butylcarbonate substrate (0.3mmol), blocking and reaction at 65 ℃ for 7 h. After completion of the reaction, the temperature was lowered to room temperature, the solvent was removed by a rotary evaporator, a saturated brine (20mL) was added, extraction was performed with ethyl acetate 3 times, the combined organic phases were washed with a saturated brine (2X 10mL) and then with anhydrous Na2SO4Drying to obtain the target compound with hydrogen nuclear magnetic yield of 73% (taking 1,1,2, 2-tetrachloroethane as an internal standard).
Example 29
2' -Phenylcyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 1)
The same procedures used in example 24 were repeated except for changing the ligand 1, 3-bis (diphenylphosphino) propane used in example 24 to 0.06mmol of triphenylphosphine, to obtain a hydrogen nuclear magnetic yield of 82% (using 1,1,2, 2-tetrachloroethane as an internal standard) of the objective compound.
Example 30
2' -Phenylcyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 1)
The procedure was carried out in the same manner as in example 24 except for replacing the ligand 1, 3-bis (diphenylphosphino) propane in example 24 with 0.06mmol of tri-n-butylphosphine, to obtain a target compound with a hydrogen nuclear magnetic yield of 78% (using 1,1,2, 2-tetrachloroethane as an internal standard).
Example 31
2' -Phenylcyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 1)
The procedure was carried out in the same manner as in example 19 except for replacing the ferrous trifluoromethanesulfonate with the same molar amount of ferrous bromide in example 19 to obtain a hydrogen nuclear magnetic yield of 56% of the objective compound (using 1,1,2, 2-tetrachloroethane as an internal standard).
Example 32
2' -Phenylcyclopropyl-4, 4,5, 5-tetramethyl-1, 3,2- (dioxaborole) cyclopentane (Compound 1)
The procedure was carried out in the same manner as in example 19 except for replacing the ferrous trifluoromethanesulfonate with the same molar amount of ferrous acetate in example 19 to obtain a hydrogen nuclear magnetic yield of 54% (using 1,1,2, 2-tetrachloroethane as an internal standard) of the objective compound.

Claims (9)

1. A method for preparing a cyclopropyl borate compound based on iron catalysis is characterized in that: in a solvent, taking a compound shown in a general formula II and a pinacol ester of diboronic acid as raw materials, reacting according to the following reaction formula in the presence of ferric salt and alkali to obtain a compound shown in a general formula I,
Figure FDA0001603895200000011
wherein the content of the first and second substances,
R1is selected from
Figure FDA0001603895200000012
Wherein n is 1-5;
R2is selected from R4OCOO-、(EtO)2POO-、MeCOO-；
R3Selected from H, C1-C6 alkyl, phenyl, halogen, trifluoromethyl, trifluoromethoxy, phenoxy, acetyl, C1-C4 alkoxy;
R4selected from C1-C4 alkyl;
the ferric salt is at least 1 selected from ferrous chloride, ferric chloride, ferrous bromide, ferric acetylacetonate, ferrous acetate and ferrous trifluoromethanesulfonate;
the alkali is selected from at least 1 of potassium tert-butoxide, sodium tert-butoxide, lithium tert-butoxide, sodium methoxide, lithium methoxide and potassium methoxide;
the solvent is at least 1 selected from tetrahydrofuran, methyl tert-butyl ether, 1, 4-dioxane, n-butyl ether, isopropyl ether, dimethyl sulfoxide and toluene.
2. The iron-based catalytic process for preparing cyclopropyl boronic acid ester compounds of claim 1, wherein: the R is2Is t-BuOCOO-, MeOOCOO-, (EtO)2POO-or MeCOO-.
3. The iron-based catalytic process for preparing cyclopropyl boronic acid ester compounds of claim 1, wherein: the R is3Is H, methyl, methoxy, halogen, isopropyl, trifluoromethoxy, phenyl, phenoxy or acetyl.
4. The iron-based catalytic process for preparing cyclopropyl boronic acid ester compounds of claim 1, wherein: the amount of the alkali substance is 0.6-2 times of that of the compound shown in the general formula II.
5. The iron-based catalytic process for preparing cyclopropyl boronic acid ester compounds of claim 1, wherein: the amount of the matter of the diboron pinacol ester is 1-2 times of that of the compound shown in the general formula II.
6. The iron-based catalytic process for preparing cyclopropyl boronic acid ester compounds of claim 1, wherein: the amount of the ferric salt substance is 1-10% of the amount of the compound substance shown in the general formula II.
7. The iron-based catalytic process for preparing cyclopropyl boronic acid ester compounds of claim 1, wherein: adding a ligand selected from at least 1 of triphenylphosphine, tri-n-butylphosphine, 4, 5-bis-diphenylphosphine-9, 9-dimethylxanthene, 4-dimethylaminopyridine, 1, 2-bis (diphenylphosphine) ethane, 1, 2-bis (diphenylphosphine) propane, triethyl phosphite, tetramethylethylenediamine in the presence of an iron salt and a base.
8. The iron-based catalytic process for preparing cyclopropyl boronic acid ester compounds of claim 7, wherein: the amount of the ligand substance is 10-20% of the amount of the compound substance shown in the general formula II.
9. The iron-based catalytic preparation method of a cyclopropylboronic acid ester compound according to any one of claims 1 to 8, wherein: the reaction temperature is 25-solvent reflux temperature, and the reaction time is 7-48 h.
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Enantioselective Synthesis oftrans-Aryl- and -Heteroaryl-Substituted Cyclopropylboronates by Copper(I)-Catalyzed Reactions of Allylic Phosphates with a Diboron Derivative;Chongmin Zhong et al.;《J. AM. CHEM. SOC》;20100408;第132卷;第11440页图1，第11441页图2 *

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