CN102558207A - Substituted alkyl borate compounds and preparation method thereof - Google Patents
Substituted alkyl borate compounds and preparation method thereof Download PDFInfo
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- 0 CC(C)OC(C1O*OC1C(OC(C)C)=O)=O Chemical compound CC(C)OC(C1O*OC1C(OC(C)C)=O)=O 0.000 description 3
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Abstract
The invention provides a substituted alkyl borate compound disclosed as A, wherein R1 and R2 respectively independently represent hydrogen atom or C1-C10 alkyl group or substituted C1-C10 alkyl group; or R1 and R2 commonly represent cyclic alkyl group or substituted cyclic alkyl group, and the group represents borate group. The invention provides the substituted alkyl borate compound having high developed functional group compatibility, being capable of maintaining high reaction activity, being convenient for suzuki coupling, and being capable of introducing different substituted alkyl groups, and provides a preparation and application of the substituted alkyl borate compound.
Description
Technical field
The present invention relates to the alkylboronic acids ester type compound containing substitution that a kind of formula A is represented, the compound can be widely used in Suzuki (suzuki) coupling reaction, for building alkyl substituents groups.
Background technology
Alkylboronic acids ester type compound is the reagent for being widely used in building alkyl substituents groups in Suzuki (suzuki) coupling reaction.The synthetic method of early stage mainly has：
First, borane reagent addition
Suzuki has two methods the Chemisty Letters (chemical communication) of 89 years is inner：
The method mentioned in Adv.Synth.Catal. (synthetic catalyst forward position) 2005,347,50-54 is also similar.
It is also addition of the boron hydrogen reagent carried out under Zr and Rh catalysis to alkene in J.Am.Chem.Soc. (American Chemical Society's proceedings) 1996,118,909-910.
Also some be conjugated diene addition：
J.AM.CHEM.SOC.2009, is the boron hydrogen addition of Fe catalysis in 131,12915-12917.
Secondly there is the conjugated diene of copper catalysis and be conjugated the addition reaction of ketene, but nucleopilic reagent is the boron of pinacol two, J.AM.CHEM.SOC. (American Chemical Society's proceedings) 2010,132,1226-1227 and Org.Lett. (organic chemistry communication), Vol.12, No.21,2010：
2nd, the substitution of allylic
The method mentioned in Angew.Chem.Int.Ed. (Germany is with chemistry) 2009,48,6317-6319：
3rd, synthesized by alkyl boron reagent：
In J.C.S.CHEM.COMM. (chemical communication), 1977：
4th, the C-H activation boron esterifications of alkane terminal hydrogen
This method is mainly what Hartwig their groups were done：
5th, reacted using RMgBr and borate
In place of each raising in need of above several method, the first boron hydrogen reagent mainly used, this kind of reagent is expensive, and storage and using inconvenient, and several in addition can only then be confined to the substrate of conjugated alkene using two borane reagents.It is also for second substrate spectrum limitation, the third is compared to better, but this reaction is what is carried out under 500W high voltage mercury lamp radiation, it is difficult to generally use；4th kind, the selectivity of c h bond is a problem, and can only activated end groups c h bond；5th kind used high activity RMgBr so that compatibility becomes very poor, and this is an obvious shortcoming.
Therefore, this area lacks a kind of substitution alkylboronic acids ester compounds, and the compound has been avoided that the shortcoming of prior art, and functional group compatibility is high, and can keep high reactivity, is easy to be coupled by suzuki, introduces different substitution alkyl groups.
Therefore, this area is in the urgent need to exploitation functional group compatibility height, and can keep high reactivity, is easy to be coupled by suzuki, can introduce different substitution alkylboronic acids ester compounds of substitution alkyl group and preparation method thereof.
The content of the invention
The first object of the present invention is to obtain functional group compatibility height, and can keep high reactivity, is easy to be coupled by suzuki, can introduce different substitution alkylboronic acids ester compounds of substitution alkyl group and preparation method thereof.
The second object of the present invention is to obtain functional group compatibility height, and can keep high reactivity, is easy to be coupled by suzuki, can introduce the preparation methods of the substitution alkylboronic acids ester compounds of different substitution alkyl groups.
The third object of the present invention is to obtain the application that substitution alkylboronic acids ester compounds are coupled in suzuki.
Replace alkylboronic acids ester compounds there is provided one kind in the first aspect of the present invention, the compound is as shown in following formula A：
Wherein
R1And R2Represent respectively it is independent represent hydrogen atom either C1-C10 alkyl or substituted C1-C10 alkyl or；
R1And R2It is common to represent cyclic alkyl or substituted cyclic alkyl；
It is described
Group represents borate group.
In a preference, the substitution functional group includes the groups such as ester group, ketone group, alkenyl, cyano group, halogen, hydroxyl, alkoxy, aromatic radical, heterocyclic group, amino, amide groups." the substituted C1-C10 alkyl " refers to there is one or more substitution functional groups on C1-C10 alkyl.Similar, " substituted cyclic alkyl " refers to there is one or more substitution functional groups on the cyclic alkyl.
It is described in a preferenceGroup is represented with five-membered ring structure borate group；Or hexatomic ring borate group.
In the specific embodiment of the present invention, the formula A's
The structural formula of group is as follows：
The second aspect of the present invention provides a kind of preparation method of described compound, and it comprises the following steps：
Double boric acid ester compounds of Formulas I are provided：
The alkyl-substituted compound of Formula II is provided,
The R1、R2With
The definition of group is as claimed in claim 1；The X be chlorine atom, bromine atoms, iodine atom or p-methyl benzenesulfonic acid ester group,
Double boric acid ester compounds of the Formulas I and the alkyl-substituted compound of Formula II are reacted under cuprous salt catalysis and alkali effect in solvent, obtain compound as claimed in claim 1.
In the specific embodiment of the present invention, double boric acid ester compounds of the Formulas I are shown below：
In the specific embodiment of the present invention, the cuprous salt refers to cuprous iodide, cuprous bromide, stannous chloride, the combination of cuprous cyanide internal heat.
In the specific embodiment of the present invention, described alkali refers to alkali alcoholate.
In the specific embodiment of the present invention, described solvent is non-protonic polar solvent.
In a preference, the non-protonic polar solvent is one or more of combinations in dioxane, tetrahydrofuran, acetonitrile, dimethylformamide, 1-METHYLPYRROLIDONE, dimethyl acetamide.
In the specific embodiment of the present invention, when X is bromine atoms, the phosphorus part that catalytic amount is added during the course of the reaction promotes the progress of reaction；
And when X is chlorine atom or p-methyl benzenesulfonic acid ester group, the salt compounded of iodine that catalytic amount is added during the course of the reaction promotes the progress of reaction.
In the specific embodiment of the present invention, the Phosphine ligands refer to trisubstituted organic phosphorus compound；Wherein described salt compounded of iodine refers to the quaternary ammonium salt containing iodine anion.
Another aspect of the present invention provides application of the substitution alkylboronic acids ester compounds of the present invention in for Suzuki (suzuki) coupling reaction.
Embodiment
The present inventor is by in-depth study extensively, by improving preparation technology, obtain a kind of substitution alkylboronic acids ester compounds, the compound has been avoided that the shortcoming of prior art, functional group compatibility is high, and high reactivity can be kept, is easy to be coupled by suzuki, different substitution alkyl groups are introduced.The present invention is completed on this basis.
As used herein, described " alkyl ", unless otherwise indicated, refers to the straight or branched alkane containing 1-10 carbon atom.For example, alkyl includes but is not limited to methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, the tert-butyl group.
As used herein, described " aromatic radical ", unless otherwise indicated, refers to can thering is 1-4 substituent on the mononuclear aromatics containing 6 carbon atoms, the double ring arene of 10 carbon atoms, the thrcylic aromatic hydrocarbon of 14 carbon atoms, and each ring.For example, aryl includes but is not limited to phenyl, naphthyl, anthryl.
As used herein, described " halogen ", unless otherwise indicated, refers to fluorine, chlorine, bromine, iodine and halogenoid group, more specifically refers to chlorine, bromine, iodine or p-methyl benzenesulfonic acid ester group.
As used herein, described " heterocyclic group " includes " Heterocyclylalkyl " and " heteroaromatic ".Described " Heterocyclylalkyl " refers to containing 2-12 carbon atom and at least contains the undersaturated cyclic hydrocarbon of a heteroatomic saturation or part in N, O, S.Described " heteroaromatic ", refers to the mononuclear aromatics of 5-8 atom, the double ring arene of 8-12 atom, the thrcylic aromatic hydrocarbon of 11-14 atom, and contain one or more hetero atoms (such as N, O, S)." heteroaromatic " includes but is not limited to pyridine radicals, furyl, imidazole radicals, benzimidazolyl, pyrimidine radicals, thienyl, quinolyl, indyl, thiazolyl.
As used herein, described ester group, ketone group, can connect " alkyl " or " aromatic radical " on alkenyl.
As used herein, described " alkoxy " is referred to " alkyl-O ".
Unless specific instructions, various raw materials of the invention can be by being commercially available；Or prepared according to the conventional method of this area.Unless otherwise defined or described herein, all specialties used herein are identical with meaning known to those skilled in the art with scientific words.In addition any method similar or impartial to described content and material all can be applied in the inventive method.
It is described in detail to various aspects of the present invention below：
Replace alkylboronic acids ester compounds
Formula A compounds
One kind substitution alkylboronic acids ester compounds, the compound is as shown in following formula A：
Wherein
R1And R2Represent respectively it is independent represent hydrogen atom either C1-C10 alkyl or substituted C1-C10 alkyl or；
R1And R2It is common to represent cyclic alkyl or substituted cyclic alkyl.
The substitution functional group includes the groups such as ester group, ketone group, alkenyl, cyano group, halogen, hydroxyl, alkoxy, aromatic radical, heterocyclic group, amino, amide groups.
In a preference, the formula A
Represent following structural formula.
Formula A compound example illustrated example is as follows：
Preparation method
The preparation method of compound of the present invention, comprises the following steps：
Double boric acid ester compounds of Formulas I are provided：
The alkyl-substituted compound of Formula II is provided,
The R1And R2It is defined as described above；The X be chlorine atom or bromine atoms or iodine atom or p-methyl benzenesulfonic acid ester group,
Double boric acid ester compounds of the Formulas I and the alkyl-substituted compound of Formula II are reacted in the case where cuprous salt is catalyzed and alkali is acted in applicable solvent, obtain compound of the present invention.
Double boric acid ester compounds of Formulas I
In a detailed embodiment, double boric acid ester compounds of the Formulas I are shown below：
Formula (II) compound
The specific example of formula (II) compound is as follows：
N- Hexyl Bromide, 7- iodine enanthic ethers, 6- bromine nitrile-hexyls, iodo -4- hexahydrotoluenes, β-chloro -2- furans ethane, 5- iodo n-amyl alcohols, ethyoxyl p-methyl benzenesulfonic acid glycol ester, 10- chloro -1- quinenes, (5- chlorine amyl group)-phthalic amide, the own ester of 3- p-methyl benzenesulfonic acid, N- Methyl-N-phenyl -4- bromine butyramides, 1- tri isopropyl siloxany -6- bromohexanes, suberyl iodine, cyclopenta chlorine, cyclohexyl bromide, adjacent fluorobenzyl bromide, the bromo- 2 pentanones of 5-, cyclopentyl-methyl iodine, to bromobenzyl bromine, between benzyl chloride iodine, 6- chlorine iodohexanes, 1, 6- dibromo-hexanes, two rings [2, 2, 1] -2- heptyl bromine, β-p-methyl benzenesulfonic acid -2- thiophene ethyl esters, the bromo- N- tert-butoxycarbonyls hexahydropyridines of 4-, N- (6- chlorine hexyl) indoles, beta-bromine ethylbenzene.
Cuprous salt
In a detailed embodiment, the cuprous salt refers to cuprous iodide or cuprous bromide or stannous chloride or cuprous cyanide.
The cuprous salt of the present invention can also be that trifluoromethanesulfonic acid is cuprous, and thiophenedicarboxylic acid is cuprous.
Alkali
In a detailed embodiment, described alkali refers to alkali alcoholate.
The alkali of the present invention can also be and (be only applicable to alkali alcoholate).
Solvent
In a detailed embodiment, described solvent is non-protonic polar solvent.
In a preference, the non-protonic polar solvent is one or more of combinations in dioxane, tetrahydrofuran, acetonitrile, dimethylformamide, 1-METHYLPYRROLIDONE, dimethyl acetamide.
Other can promote the process conditions of reaction
In a detailed embodiment, when X is bromine atoms, the progress that some phosphorus parts promote reaction is added during the course of the reaction；
And when X is chlorine atom or p-methyl benzenesulfonic acid ester group, the progress that some salt compounded of iodine promote reaction is added during the course of the reaction.
In a detailed embodiment, the Phosphine ligands refer to trisubstituted organic phosphorus compound；Wherein described salt compounded of iodine refers to the quaternary ammonium salt containing iodine anion.
Above-mentioned synthetic method is the synthetic route of part of compounds of the present invention, according to above-mentioned example, those skilled in the art can synthesize other compounds of the present invention by adjusting different methods, or, those skilled in the art can synthesize the compound of the present invention according to existing known technology.The compound of synthesis can be further purified with further by modes such as column chromatography, high performance liquid chromatography or crystallizations.
It is helpful to synthesis application compound to synthesize chemical improvement, protection functional group methodology (protection is deprotected); and it is well known in the prior art technology; such as R.Larock; ComprehensiveOrganic Transformations, VCH Publishers (1989)；T.W.Greene and P.G.M.Wuts, Protective Groups in Organic Synthesis, the third edition, John Wiley and Sons (1999)；L.Fieser and M.Fieser, Fieser and Fieser ' s Reagents for Organic Synthesis, John Wiley and Sons (1994)；And have disclosure in L.Paquette, ed., Encyclopedia of Reagents for Organic Synthesis, John Wiley and Sons (1995).
Other aspects of the present invention, due to this disclosure, are obvious to those skilled in the art.
With reference to specific embodiment, the present invention is expanded on further.It should be understood that these embodiments are only illustrative of the invention and is not intended to limit the scope of the invention.The experimental method of unreceipted actual conditions in the following example, generally according to normal condition, or according to the condition progress proposed by manufacturer.Unless otherwise indicated, otherwise all number is parts by weight, and all percentages are weight percentage, and described polymer molecular weight is number-average molecular weight.
Unless otherwise defined or described herein, all specialties used herein are identical with meaning known to those skilled in the art with scientific words.In addition any method similar or impartial to described content and material all can be applied in the inventive method.
Embodiment
The following examples are that the present invention is illustrated in more detail.
Embodiment 1：
Under argon gas protection; the connection pinacol borate of 0.25mmol 7- iodine enanthic ether and 0.375mmol is mixed with 0.5ml tetrahydrofurans, 0.025mmolCuI and 0.5mmol tert-butyl alcohol lithiums, room temperature (25 DEG C) stirring reaction 24h is added; product, yield 86% are purified to obtain after reaction.
Detect that data are as follows：
1H NMR(CDCl3, 400MHz) and δ 4.09 (q, J=7.1Hz, 2H), 2.25 (t, J=7.6Hz, 2H), 1.57-1.62 (m, 2H), 1.37-1.40 (m, 2H), 1.26-1.29 (m, 4H), 1.20-1.24 (m, 15H), 0.73 (t, J=7.6Hz, 2H) ppm；13C NMR(CDCl3, 100MHz) and δ 173.9,82.9,60.2,34.5,32.0,29.0,25.0,24.9,23.9,14.3ppm；11B NMR(CDCl3, 102.7MHz) and δ 33.95ppm.HRMS theoretical values C15H29BO4(M+)：284.2159；Test value：284.2154.
Embodiment 2：
Under argon gas protection; the connection pinacol borate of 0.25mmol 6- bromines nitrile-hexyl and 0.375mmol is mixed with 0.5ml dimethylformamides; add 0.025mmolCuI, 0.5mmol lithium methoxide and 0.0325mmol triphenylphosphines; room temperature (25 DEG C) stirring reaction 18h; product, yield 85% are purified to obtain after reaction.
Detect that data are as follows：
1H NMR(CDCl3, 400MHz) and (t, J=7.3Hz, the 2H) ppm of δ 2.33 (t, J=7.2Hz, 2H), 1.62-1.68 (m, 2H), 1.43-1.47 (m, 4H), 1.25 (s, 12H), 0.79；13C NMR(CDCl3, 100MHz) and δ 119.8,83.0,31.2,29.7,25.2,24.8,23.1,17.0ppm；11B NMR(CDCl3, 102.7MHz) and δ 34.07ppm.HRMS theoretical values C12H22BNO2(M+)：223.1744；Test value：223.1746.
Embodiment 3：
Under argon gas protection; the connection pinacol borate of 0.25mmol N- (6- chlorine hexyl) indoles and 0.375mmol is mixed with 0.5ml tetrahydrofurans; add 0.025mmolCuI, 0.5mmol tert-butyl alcohol lithium and 0.25mmol tetrabutylammonium iodides; 60 DEG C of stirring reaction 24h; product, yield 76% are purified to obtain after reaction.
Detect that data are as follows：
1H NMR(CDCl3, 400MHz) and δ 7.61-7.63 (m, 1H), 7.34 (d, J=8.2Hz, 1H), 7.19 (ddd, J=8.2,7.1,1.1Hz, 1H), 7.06-7.10 (m, 2H), 6.47 (d, J=2.9Hz, 1H), 4.10 (t, J=7.2Hz, 2H), 1.79-1.86 (m, 2H), 1.28-1.41 (s, 6H), 1.23 (s, 12H), 0.76 (t, J=7.5Hz, 2H) ppm；13C NMR(CDCl3, 100MHz) and δ 136.0,128.6,127.8,121.3,120.9,119.1,109.4,100.8,82.9,46.4,31.9,31.2,30.2,26.8,24.8,23.9ppm；11B NMR(CDCl3, 102.7MHz) and δ 34.3ppm.HRMS theoretical values C20H30BNO2(M+)：327.2370, test value：327.2373.
Embodiment 4：
Under argon gas protection; the connection pinacol borate of 0.25mmol β-p-methyl benzenesulfonic acid -2- thiophene ethyl ester and 0.375mmol is mixed with 0.5ml acetonitriles; add 0.025mmolCuI, 0.5mmol tert-butyl alcohol lithium and 0.25mmol tetrabutylammonium iodides; 60 DEG C of stirring reaction 24h; product, yield 74% are purified to obtain after reaction.
Detect that data are as follows：
1H NMR(CDCl3, 400MHz) and δ 7.07 (dd, J=5.1,1.1Hz, 1H), 6.89 (dd, J=5.1,3.4Hz, 1H), 6.79 (m, 1H), 2.96 (t, J=7.6Hz, 2H), 1.20-1.26 (m, 14H) ppm；13CNMR(CDCl3, 100MHz) and δ 147.8,126.5,123.4,122.6,83.2,24.8,24.4ppm；11BNMR(CDCl3, 102.7MHz) and δ 33.9ppm.HRMS theoretical values C12H19BO2S(M+)：238.1199；Test value：238.1196.
Embodiment 5：
Under argon gas protection; the duplex neopentyl glycol borate of 0.25mmol 1- hexyl bromides and 0.375mmol is mixed with 0.5ml acetonitriles, 0.025mmolCuI, 0.5mmol lithium methoxide and 0.025mmol triphenylphosphines, 25 DEG C of stirring reaction 24h is added; product, yield 83% are purified to obtain after reaction.
Detect that data are as follows：
1H NMR(CDCl3, 400MHz) and (t, J=7.5Hz, the 3H) ppm of δ 3.59 (s, 4H), 1.26-1.36 (m, 8H), 0.95 (s, 6H), 0.87 (t, J=6.8Hz, 2H), 0.70；13C NMR(CDCl3, 100MHz) and δ 71.0,31.2,30.8,20.6,23.1,21.8,20.8,13.1ppm；11B NMR(CDCl3, 102.7MHz) and δ 30.4ppm.HRMS theoretical values C11H23BO2(M+)：198.1791；Test value：198.1787.
Embodiment 6：
Under argon gas protection; the duplex neopentyl glycol borate of the amyl- 2- ketone of 0.25mmol 5- bromines and 0.375mmol is mixed with 0.5ml acetonitriles, 0.025mmolCuI, 0.5mmol lithium methoxide and 0.025mmol triphenylphosphines, 25 DEG C of stirring reaction 24h is added; product, yield 84% are purified to obtain after reaction.
Detect that data are as follows：
1H NMR(CDCl3, 400MHz) and (t, J=7.8Hz, the 2H) ppm of δ 2.37 (t, J=7.5Hz, 2H), 2.06 (s, 3H), 1.59-1.67 (m, 2H), 1.17 (s, 12H), 0.71；13C NMR(CDCl3, 100MHz) and δ 209.2,83.0,43.0,29.8,24.8,18.6ppm.11B NMR(CDCl3, 102.7MHz) and δ 33.7ppm.HRMS theoretical values C11H21BO3(M+)：212.1584；Test value：212.1588.
Embodiment 7：
Under argon gas protection; the duplex neopentyl glycol borate of 0.25mmol 2- (4- bromines butoxy)-naphthalenes and 0.375mmol is mixed with 0.5ml acetonitriles; add 0.025mmolCuI, 0.5mmol lithium methoxide and 0.025mmol triphenylphosphines; 25 DEG C of stirring reaction 24h; product, yield 71% are purified to obtain after reaction.
Detect that data are as follows：
1H NMR(CDCl3, 400MHz) and δ 7.66-7.74 (m, 3H), 7.40 (ddd, J=8.2,6.9,1.3Hz, 1H), 7.30 (ddd, J=8.1,6.9,1.2Hz, 1H), 7.10-7.15 (m, 2H), 4.06 (t, J=6.6Hz, 2H), 1.82-1.89 (m, 2H), 1.59-1.67 (m, 2H), 1.24 (s, 12H), 0.88 (t, J=7.9Hz, 2H) ppm；13CNMR(CDCl3, 100MHz) and δ 157.1,134.8,129.2,128.9,127.6,126.7,126.2,123.4,119.1,106.5,83.0,67.8,31.7,24.8,20.7ppm；11B NMR(CDCl3, 102.7MHz) and δ 34.2ppm.HRMS theoretical values C20H27BO3(M+)：326.2053；Test value：326.2058.
Embodiment 8：
Synthesis
Under argon gas protection; the duplex neopentyl glycol borate of the bromo- 1- decene of 0.25mmol 10- and 0.375mmol is mixed with 0.5ml acetonitriles, 0.025mmolCuI, 0.5mmol lithium methoxide and 0.025mmol triphenylphosphines, 25 DEG C of stirring reaction 24h is added; product, yield 77% are purified to obtain after reaction.
Detect that data are as follows：
1H NMR(CDCl3, 400MHz) and δ 5.81 (ddt, J=16.910.26.7Hz, 1H), 4.90-5.01 (m, 2H), 2.00-2.06 (m, 2H), 1.26-1.41 (m, 12H), 1.24 (s, 12H) 0.76 (t, J=7.7Hz, 2H) ppm；13C NMR(CDCl3, 100MHz) and δ 139.3,114.0,82.8,33.8,32.4,29.4,29.3,29.1,29.0,24.8,24.0ppm；11B NMR(CDCl3, 102.7MHz) and δ 34.0ppm.HRMS theoretical values C16H31BO2(M+)：266.2417；Test value：266.2414.
Embodiment 9：
Under argon gas protection; the duplex neopentyl glycol borate of 0.25mmol 6- bromines hexanol and 0.375mmol is mixed with 0.5ml acetonitriles, 0.025mmolCuI, 0.5mmol lithium methoxide and 0.025mmol triphenylphosphines, 25 DEG C of stirring reaction 24h is added; product, yield 53% are purified to obtain after reaction.
Detect that data are as follows：
1H NMR(CDCl3, 400MHz) and δ 3.63 (t, J=6.7Hz；2H), (t, J=7.6Hz, the 2H) ppm of 2.04 (s, 1H), 1.53-1.60 (m, 2H), 1.40-1.44 (m, 2H), 1.32-1.34 (m, 4H), 1.24 (s, 12H), 0.78；13C NMR(CDCl3, 100MHz) and δ 82.9,63.1,32.7,32.1,25.5,24.8,23.9ppm；11B NMR(CDCl3, 102.7MHz) and δ 34.4ppm.HRMS theoretical values C12H25BO3(M+)：228.1897；Test value：228.1895.
Embodiment 10：
Under argon gas protection; by 0.25mmol 2- (2- bromoethyls)-[1; 3] dioxanes and 0.375mmol duplex neopentyl glycol borate are mixed with 0.5ml acetonitriles; add 0.025mmolCuI, 0.5mmol lithium methoxide and 0.025mmol triphenylphosphines; 25 DEG C of stirring reaction 24h; product, yield 62% are purified to obtain after reaction.
Detect that data are as follows：
1H NMR(CDCl3, 400MHz) and (t, J=7.7Hz, the 2H) ppm of δ 4.89 (t, J=4.4Hz, 1H), 3.83-3.96 (m, 4H), 1.76-1.80 (m, 2H), 1.24 (s, 12H), 0.84；13C NMR(CDCl3, 100MHz) and δ 105.3,83.0,65.0,28.3,25.0,24.8ppm；11B NMR(CDCl3, 102.7MHz) and δ 33.8ppm.HRMS theoretical values C11H21BO4(M+)：228.1533；Test value：228.1537.
Embodiment 11：
Synthesis
Under argon gas protection; the duplex neopentyl glycol borate of 0.25mmol 4- bromines piperidines -1- carboxylic acid tert-butyl esters and 0.375mmol is mixed with 0.5ml acetonitriles; add 0.025mmolCuI, 0.5mmol lithium methoxide and 0.025mmol triphenylphosphines; 37 DEG C of stirring reaction 24h; product, yield 61% are purified to obtain after reaction.
Detect that data are as follows：
1H NMR(CDCl3, 400MHz) and 3.70 (d, J=11.7Hz, 2H), 2.78-2.93 (m, 2H), 1.51-1.59 (m, 2H), 1.39-1.46 (m, 2H), 1.37 (s, 9H), 1.16 (s, 12H), 1.00-1.09 (m, 1H) ppm；13C NMR(CDCl3, 100MHz) and δ 153.8,82.1,78.0,27.5,26.0,23.7,43.8 (br) ppm.11B NMR(CDCl3, 102.7MHz)：34.9ppm.HRMS theoretical values C16H30BNO4(M+)：311.2268；Test value：311.2274.
Embodiment 12：
Synthesis
Under argon gas protection; the duplex neopentyl glycol borate of 0.25mmol 7- (3- bromines butoxy) -4- methyl-coumarins and 0.375mmol is mixed with 0.5ml acetonitriles; add 0.025mmolCuI, 0.5mmol lithium methoxide and 0.025mmol triphenylphosphines; 25 DEG C of stirring reaction 24h; product, yield 76% are purified to obtain after reaction.
Detect that data are as follows：
1H NMR(CDCl3, 400MHz) and 7.47 (d, J=8.7Hz, 1H), 6.84-6.87 (m, 2H), 6.12 (d, J=1.1Hz, 1H), 4.01-4.11 (m, 2H), 2.39 (d, J=1.1Hz, 3H), 1.97 (dt, J=13.8,6.8Hz, 1H), 1.80 (dt, J=13.6,6.6Hz, 1H), 1.25 (m, 13H), 1.06 (d, J=7.5Hz, 3H) ppm；13CNMR(CDCl3, 100MHz) and δ 162.4,161.4,155.4,152.5,125.4,113.4,112.8,111.8,10l.4,83.2,68.0,32.1,24.8,24.7,18.6,15.5ppm.11B NMR(CDCl3, 102.7MHz)：34.7ppm.HRMS theoretical value C20H27BO5(M+)：358.1952；Test value：358.1959.
Embodiment 13：
Under argon gas protection, by the bromo- DMAs of 0.25mmol 4- and 0.375mmol
(embodiment 2 is obtained) and 0.5ml toluene, 0.05mL water mixing, adds 0.005mmol Pd2(dba)3, 0.75mmol sodium tert-butoxides and 0.01mmol 2- dicyclohexylphosphontetrafluoroborates -2 ', 6 '-diisopropoxy -1,1 '-biphenyl, 80 DEG C of stirring reaction 24h purify to obtain product, yield 81% after reaction.
Detect that data are as follows：
1H NMR(CDCl3, 400MHz) and δ 7.06 (d, J=8.3Hz, 2H), 6.71 (d, J=8.4Hz, 2H), 2.93 (s, 6H), 2.55 (t, J=7.5Hz, 2H), 2.32 (t, J=7.2Hz, 2H), 1.61-1.70 (m, 4H), 1.47-1.52 (m, 2H) ppm；13C NMR(CDCl3, 100MHz) and 149.1,130.2,128.9,119.8,113.0,40.9,34.5,30.9,28.3,25.3,17.1ppm.HRMS theoretical value C of δ14H20N2(M+)：216.1626；Test value：216.1634.
Embodiment 14：
Under argon gas protection, by 0.25mmol 4- trifluoromethyl-bromo-benzenes and 0.375mmol
(embodiment 2 is obtained) and 0.5ml toluene, 0.05mL water mixing, adds 0.005mmol Pd2(dba)3, 0.75mmol sodium tert-butoxides and 0.01mmol 2- dicyclohexylphosphontetrafluoroborates -2 ', 6 '-diisopropoxy -1,1 '-biphenyl, 80 DEG C of stirring reaction 24h purify to obtain product, yield 82% after reaction.
Detect that data are as follows：
1H NMR(CDCl3, 400MHz) and δ 7.53 (d, J=8.1Hz, 2H), 7.28 (d, J=8.0Hz, 2H), 2.69 (t, J=7.7Hz, 2H), 2.33 (t, J=7.1Hz, 2H), 1.64-1.72 (m, 4H), (1.47-1.53 m, 2H) ppm；13C NMR(CDCl3, 100MHz) and δ 146.1, (128.7,128.4,128.1,127.8, q, J=32.3Hz) 125.3 (q, J=3.8Hz), (128.4,125.7,123.0,120.3, q, J=271.9Hz), 119.6,35.4,30.3,28.2,25.2,17.0ppm.HRMS theoretical value C13H14F3N(M+)：241.1078；Test value：241.1074.
The embodiment provided should can support the creativeness of the present invention, namely " functional group compatibility is high, and can keep high reactivity, is easy to be coupled by suzuki, can introduce different substitution alkyl groups ".
The foregoing is merely illustrative of the preferred embodiments of the present invention, it is not limited to the substantial technological context of the present invention, the substantial technological content of the present invention is broadly to be defined in the right of application, any technology entities that other people complete or method, if identical with defined in the right of application, also or a kind of equivalent change, it will be considered as being covered by among the right.
All documents referred in the present invention are all incorporated as reference in this application, are individually recited just as each document as with reference to such.In addition, it is to be understood that after the above of the present invention has been read, those skilled in the art can make various changes or modifications to the present invention, and these equivalent form of values equally fall within the application appended claims limited range.
Claims (10)
1. one kind substitution alkylboronic acids ester compounds, it is characterised in that the compound is as shown in following formula A：
Wherein
R1And R2Represent respectively it is independent represent hydrogen atom either C1-C10 alkyl or substituted C1-C10 alkyl or；
R1And R2It is common to represent cyclic alkyl or substituted cyclic alkyl；
It is described
Group represents borate group.
2. compound as claimed in claim 1, it is characterised in that the formula A's
The structural formula of group is as follows：
3. a kind of preparation method of compound as claimed in claim 1, it is characterised in that comprise the following steps：
Double boric acid ester compounds of Formulas I are provided：
The alkyl-substituted compound of Formula II is provided,
The R1、R2With
The definition of group is as claimed in claim 1；The X be chlorine atom, bromine atoms, iodine atom or p-methyl benzenesulfonic acid ester group,
Double boric acid ester compounds of the Formulas I and the alkyl-substituted compound of Formula II are reacted under cuprous salt catalysis and alkali effect in solvent, obtain compound as claimed in claim 1.
4. method as claimed in claim 3, it is characterised in that double boric acid ester compounds of the Formulas I are shown below：
5. method as claimed in claim 3, it is characterised in that the cuprous salt refers to cuprous iodide, cuprous bromide, stannous chloride, the combination of cuprous cyanide internal heat.
6. method as claimed in claim 3, it is characterised in that described alkali refers to alkali alcoholate.
7. method as claimed in claim 3, it is characterised in that described solvent is non-protonic polar solvent.
8. method as claimed in claim 3, it is characterised in that
When X is bromine atoms, the phosphorus part that catalytic amount is added during the course of the reaction promotes the progress of reaction；
And when X is chlorine atom or p-methyl benzenesulfonic acid ester group, the salt compounded of iodine that catalytic amount is added during the course of the reaction promotes the progress of reaction.
9. method as claimed in claim 8, it is characterised in that the Phosphine ligands refer to trisubstituted organic phosphorus compound；Wherein described salt compounded of iodine refers to the quaternary ammonium salt containing iodine anion.
10. a kind of application of substitution alkylboronic acids ester compounds as claimed in claim 1 in for Suzuki (suzuki) coupling reaction.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105198911A (en) * | 2015-10-20 | 2015-12-30 | 华侨大学 | Catalyzed synthesis method of alkyl boric acid ester |
| CN108383866A (en) * | 2018-04-27 | 2018-08-10 | 中国科学技术大学 | A kind of transition metal-catalyzed method for preparing ene-alkyne ylboronic acid ester |
| CN108503662A (en) * | 2018-04-27 | 2018-09-07 | 中国科学技术大学 | A kind of preparation method of ene-alkyne ylboronic acid ester |
| CN110885341A (en) * | 2019-12-17 | 2020-03-17 | 北京大学 | Boron esterification reaction method of alkyl bromide without transition metal catalysis |
-
2011
- 2011-12-14 CN CN2011104190567A patent/CN102558207A/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| CHU-TING YANG ET AL.: ""Alkylboronic Esters from Copper-Catalyzed Borylation of Primary and Secondary Alkyl Halides and Pseudohalides"", 《ANGEW. CHEM. INT. ED.》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105198911A (en) * | 2015-10-20 | 2015-12-30 | 华侨大学 | Catalyzed synthesis method of alkyl boric acid ester |
| CN108383866A (en) * | 2018-04-27 | 2018-08-10 | 中国科学技术大学 | A kind of transition metal-catalyzed method for preparing ene-alkyne ylboronic acid ester |
| CN108503662A (en) * | 2018-04-27 | 2018-09-07 | 中国科学技术大学 | A kind of preparation method of ene-alkyne ylboronic acid ester |
| CN108503662B (en) * | 2018-04-27 | 2020-08-28 | 中国科学技术大学 | Preparation method of alkynylene boric acid ester |
| CN110885341A (en) * | 2019-12-17 | 2020-03-17 | 北京大学 | Boron esterification reaction method of alkyl bromide without transition metal catalysis |
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Application publication date: 20120711 |