CN101318897B - Method for synthesizing trans-alpha-allyl-beta, gamma-unsaturated carboxylic acid ester - Google Patents
Method for synthesizing trans-alpha-allyl-beta, gamma-unsaturated carboxylic acid ester Download PDFInfo
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- CN101318897B CN101318897B CN2008100626664A CN200810062666A CN101318897B CN 101318897 B CN101318897 B CN 101318897B CN 2008100626664 A CN2008100626664 A CN 2008100626664A CN 200810062666 A CN200810062666 A CN 200810062666A CN 101318897 B CN101318897 B CN 101318897B
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- acid ester
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- unsaturated carboxylic
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- 238000000034 method Methods 0.000 title claims abstract description 22
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 12
- 125000003262 carboxylic acid ester group Chemical class [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 title 1
- 150000002148 esters Chemical class 0.000 claims abstract description 30
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims abstract description 18
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims abstract description 18
- 150000004795 grignard reagents Chemical class 0.000 claims abstract description 15
- 239000007818 Grignard reagent Substances 0.000 claims abstract description 14
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 150000001336 alkenes Chemical class 0.000 claims description 32
- 239000002253 acid Substances 0.000 claims description 28
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims description 28
- 150000001735 carboxylic acids Chemical class 0.000 claims description 19
- DLAPQHBZCAAVPQ-UHFFFAOYSA-N iron;pentane-2,4-dione Chemical compound [Fe].CC(=O)CC(C)=O DLAPQHBZCAAVPQ-UHFFFAOYSA-N 0.000 claims description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 238000007259 addition reaction Methods 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 238000006555 catalytic reaction Methods 0.000 claims description 4
- 239000007810 chemical reaction solvent Substances 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- CPLXHLVBOLITMK-UHFFFAOYSA-N Magnesium oxide Chemical class [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 3
- 238000004440 column chromatography Methods 0.000 claims description 3
- 239000012141 concentrate Substances 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 230000000694 effects Effects 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 235000002639 sodium chloride Nutrition 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 239000012074 organic phase Substances 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 9
- 150000001733 carboxylic acid esters Chemical class 0.000 abstract description 6
- 238000010189 synthetic method Methods 0.000 abstract description 5
- 230000003197 catalytic effect Effects 0.000 abstract description 4
- -1 diene magnesia salt Chemical class 0.000 abstract 4
- CDVAIHNNWWJFJW-UHFFFAOYSA-N 3,5-diethoxycarbonyl-1,4-dihydrocollidine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OCC)C1C CDVAIHNNWWJFJW-UHFFFAOYSA-N 0.000 abstract 1
- 239000011734 sodium Substances 0.000 description 23
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 10
- 239000007788 liquid Substances 0.000 description 9
- 239000000758 substrate Substances 0.000 description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
- CCERQOYLJJULMD-UHFFFAOYSA-M magnesium;carbanide;chloride Chemical compound [CH3-].[Mg+2].[Cl-] CCERQOYLJJULMD-UHFFFAOYSA-M 0.000 description 6
- 229910052742 iron Inorganic materials 0.000 description 3
- 230000000707 stereoselective effect Effects 0.000 description 2
- 101100004286 Caenorhabditis elegans best-5 gene Proteins 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a trans-alpha-allyl-belta, gamma-unsaturated carboxylic ester and a method for synthesizing the same. The method comprises the following steps that: a1,4-addition of a Grignard reagent and an allenoic ester is conducted to give a 1,3-conjugated diene magnesia salt at a temperature of minus 78 DEG C under the catalytic action of ferric acetylacetonate. The 1,3-conjugated diene magnesia salt rates with various allyl bromides under the catalytic action of cuprous iodide to give a series of trans-alpha-allyl-belta, gamma-unsaturated carboxylic ester compounds. The synthetic method has the advantages that the operation is simple, the raw materials and reagents are readily available, the reaction has high regional and vertical selectivity and can substitute two groups at the same time, the products can be separated and purified easily, and can be used to synthesize various trans-alpha-allyl-belta, gamma-unsaturated carboxylic esters.
Description
Technical field
The present invention relates to the method for a kind of synthesizing trans-alpha-allyl group-beta, gamma esters of unsaturated carboxylic acids.
Background technology
Trans α-allyl group-β, gamma-unsaturated carboxylic acid ester is one of most important intermediate in the organic synthesis, also is one of modal structural unit in the natural product, has multiple important physical activity, at biological technical field, there is huge value of exploiting and utilizing aspects such as medicine and agricultural chemicals.Because two keys are at β, the γ position, product tends to be isomerizated into stable α, β-unsaturated structure, Iron-Catalyzed Highly Regio-and Stereoselective Conjugate Addition of 2,3-Allenoates with Grignard Reagents, Zhan Lu, Guobi Chai, and Shengming Ma, J.Am.Chem.Soc.2007,129,14546-14547 has reported, Grignard reagent and 2 under iron catalysis, addition reaction can take place in 3-connection olefin(e) acid ester, uses the saturated ammonium chloride cancellation, can high zone and Stereoselective prepare cis beta, gamma-esters of unsaturated carboxylic acids.On this basis, can prepare cis α-allyl group-beta, gamma-esters of unsaturated carboxylic acids with acyl chlorides cancellation reaction, during the synthetic α-allyl group of bibliographical information-beta, gamma-esters of unsaturated carboxylic acids, two keys had only single the replacement not have cis-trans configurations (J.Org.Chem.1985 in the past, 50,1523-1529; J.Am.Chem.Soc.1985,107,1285-1293; J.Org.Chem.2003,68,9858-9860).
The synthetic method of the trans α-allyl group-beta, gamma-esters of unsaturated carboxylic acids of prior art report is extensive inadequately, and is convenient.
Summary of the invention
The purpose of this invention is to provide synthesizing trans-alpha-allyl group-beta, gamma-esters of unsaturated carboxylic acids, more extensive, convenient, effective synthetic method.
Synthesizing trans-alpha-allyl group of the present invention-β, the method of gamma-unsaturated carboxylic acid ester, under the effect of catalyzer acetyl acetone iron, addition reaction takes place with connection olefin(e) acid ester 1 and generates 1 in Grignard reagent, 3-conjugated diolefine magnesia salt 2, under cuprous iodide catalysis, react, obtain a series of high zone and the trans α-allyl group of stereoselectivity-beta, gamma-esters of unsaturated carboxylic acids 3 with various allyl bromide 98s; Reaction formula is as follows:
R
1Be aryl, R
2And R
3Be alkyl, R
4And R
5Be hydrogen or phenyl; Wherein alkyl is C
nH
2n+1(n=1-9); Aryl is phenyl and contains substituent phenyl; Wherein, occur in 2 with reacting high regioselectivity, on two keys of the close carboxyl of 3-connection olefin(e) acid ester, the R of Grignard reagent
3Group be introduced in the connection alkene middle carbon on highly-solid selectively ground with the reservation two keys on R
1Be in cis-position, allyl group is introduced in connection alkene near on the carbon of carboxyl.The steps include:
(1) in reaction flask, add catalyzer acetyl acetone iron, raw material 2,3-connection olefin(e) acid ester 1 and reaction solvent toluene, described acetyl acetone iron and 2, the equivalence ratio of 3-connection olefin(e) acid ester is 0.005～0.05: 1; Described 2,3-connection olefin(e) acid ester 1 is 0.4 (mmole) with the amount ratio of reaction solvent toluene: 5 (milliliters); Nitrogen protection is stirred down, is cooled to subzero 78 degree, presses Grignard reagent and 2, and the equivalence ratio of 3-connection olefin(e) acid ester is 1.2～3: 1, drips the tetrahydrofuran solution that contains Grignard reagent, and reaction is 1 hour under subzero 78 degree, generates intermediate 2;
(2) after step (1) reacts completely, reaction system is risen to room temperature, in reaction flask, add cuprous iodide and allyl bromide 98 again, described cuprous iodide and 2, the equivalence ratio of 3-connection olefin(e) acid ester is 0.01～0.20: 1; Described allyl bromide 98 and 2, the equivalence ratio of 3-connection olefin(e) acid ester is 5～8: 1;
(3) after step (2) reacts completely, drip saturated ammonium chloride and stop, be back to room temperature and add entry again; Use extracted with diethyl ether, organic phase is used 1% hydrochloric acid successively, and saturated sodium bicarbonate, saturated aqueous common salt are respectively washed once, uses anhydrous sodium sulfate drying again, filters, and concentrates, and rapid column chromatography obtains trans α-allyl group-beta, gamma-esters of unsaturated carboxylic acids 3.
Grignard reagent of the present invention and 2, the equivalence ratio of 3-connection olefin(e) acid ester is 1.2～3: 1, best 3: 1; Acetyl acetone iron catalyst and 2, the equivalence ratio of 3-connection olefin(e) acid ester is 0.005～0.05: 1, best 0.02: 1.
Cuprous iodide of the present invention and 2, the equivalence ratio of 3-connection olefin(e) acid ester is 0.01～0.20: 1, best 0.10: 1; Allyl bromide 98 and 2, the equivalence ratio of 3-connection olefin(e) acid ester is 5～8: 1, best 5: 1.
Of the present invention 2,3-connection olefin(e) acid ester be 4 mono-substituted 2,3-connection olefin(e) acid ester.Grignard reagent of the present invention is the one-level alkyl.
The present invention relates to a kind of trans α-allyl group-β, gamma-unsaturated carboxylic acid ester and synthetic method thereof, Grignard reagent and 2 under the effect of catalyzer acetyl acetone iron, 3-connection olefin(e) acid ester generation addition reaction generates 1, the magnesia salt of 3-conjugated diolefine, under cuprous iodide catalysis, react again with various allyl bromide 98s, obtain a series of high zone and the trans α-allyl group of stereoselectivity-β, gamma-unsaturated carboxylic acid ester, present method is simple to operate, raw material and reagent are easy to get, and reaction has the zone and the stereoselectivity of height, the easily separated purifying of product.
The present invention has overcome the drawback of traditional method, has the following advantages: 1) adopted cheap iron to make catalyzer; 2) reaction has the zone and the stereoselectivity of height; 3) can introduce two substituting groups simultaneously; 4) intermediate does not separate, and treats different things alike; 5) the easily separated purifying of product.
Innovative point of the present invention is to have developed a kind of trans α-allyl group-beta, gamma-esters of unsaturated carboxylic acids and the catalytic synthetic method of iron thereof.
The productive rate of the corresponding trans α-allyl group-beta, gamma-esters of unsaturated carboxylic acids of present method gained is 39-72%.
Embodiment
Following examples help to understand the present invention, but are not limited to content of the present invention.
Embodiment 1
Under the nitrogen, in reaction tubes, add acetyl acetone iron (0.0072 gram, 5% molar percentage, 0.02 mmole), 2-methyl-4-phenyl-2,3-divinyl acetoacetic ester (0.0838 gram, 0.4 mmole) and toluene (5 milliliters),, be cooled to subzero 78 degree, in system, drip (0.4 milliliter of the tetrahydrofuran solution of methylmagnesium-chloride, 3 equivalents, 1.2 mmoles).Finish, react after 1 hour, reaction system is risen to room temperature, in reaction flask, add cuprous iodide (0.0074 gram of catalytic amount again, 0.04 mmole) and allyl bromide 98 (0.17 milliliter, the d=1.39 grams per milliliter, 0.2420 the gram, 2 mmoles, 5 equivalents), reacted 10.5 hours.After reaction finishes, be cooled to zero degree and drip saturated ammonium chloride solution cancellation reaction.Naturally rise to room temperature and add entry, use extracted with diethyl ether, 1% hydrochloric acid, saturated sodium bicarbonate, saturated aqueous common salt is respectively washed once, and anhydrous sodium sulfate drying filters, and concentrates, rapid column chromatography gets 2-allyl group-2,3-dimethyl-4-phenyl-3 (E)-butenoic acid ethyl 0.0545 gram, and productive rate is 51%.Product is a colourless liquid.
1H?NMR(300MHz，CDCl
3)δ7.37-7.28(m，2H)，7.28-7.18(m，3H)，6.40(s，1H)，5.80-5.65(m，1H)，5.15-5.04(m，2H)，4.16(q，J＝7.2Hz，2H)，2.67-2.53(m，2H)，1.80(d，J＝1.2Hz，3H)，1.37(s，3H)，1.25(t，J＝7.2Hz，3H)；
13C?NMR(CDCl
3，75MHz)δ175.8，139.2，138.1，134.1，129.0，128.0，126.2，125.4，118.0，60.7，52.2，40.8，21.4，15.7，14.2；MS(m/z)258(M
+，15.90)，143(100)；IR(neat，cm
-1)2979，1729，1640，1600，1445，1232，1140，1099.Elemental?analysis：Calcd?for?C
17H
22O
2：C，79.03；H，8.58；Found：C，79.06；H，8.59.
Embodiment 2
Press embodiment 1 described method, different is that used substrate and reagent are: acetyl acetone iron (0.0072 gram, 0.02 mmole), 2-methyl-4-(4 '-fluorophenyl)-2,3-divinyl acetoacetic ester (0.0868 gram, 0.4 mmole), cuprous iodide (0.0077 gram, 0.04 mmole) and allyl bromide 98 (0.17 milliliter, the d=1.39 grams per milliliter, 0.2420 the gram, 2 mmoles, 5 equivalents) get 2-allyl group-2,3-dimethyl-4-(4 '-fluorophenyl)-3 (E)-butenoic acid ethyl 0.0781 gram, productive rate is 72%.Product is a colourless liquid.
1H?NMR(300MHz，CDCl
3)δ7.22-7.16(m，2H)，7.05-6.96(m，2H)，6.34(s，1H)，5.78-5.62(m，1H)，5.14-5.04(m，2H)，4.16(q，J＝7.1Hz，2H)，2.65-2.52(m，2H)，1.77(d，J＝1.2Hz，3H)，1.37(s，3H)，1.25(t，J＝7.1Hz，3H)；
13C?NMR(CDCl
3，75MHz)δ175.6，161.2(d，J＝244.7Hz)，139.3，134.03(d，J＝3.8Hz)，134.01，130.5(d，J＝7.5Hz)，124.3，118.0，114.8(d，J＝20.9Hz)，60.7，52.1，40.8，21.4，15.6，14.1；
19F?NMR(CDCl
3，282MHz)δ-116.2；MS(ESI，m/z)298.9((M+Na
+)，100)；IR(neat，cm
-1)2980，2927，1729，1641，1601，1508，1227.HRMS?calcd?for?C
17H
21O
2FNa
+(M+Na
+)299.1418，found?299.1422.
Embodiment 3
Press embodiment 1 described method, different is that used substrate and reagent are: acetyl acetone iron (0.0069 gram, 0.02 mmole), 2-methyl-4-(4 '-chloro-phenyl-)-2,3-divinyl acetoacetic ester (0.0950 gram, 0.4 mmole), cuprous iodide (0.0080 gram, 0.04 mmole) and allyl bromide 98 (0.17 milliliter, the d=1.39 grams per milliliter, 0.2420 the gram, 2 mmoles, 5 equivalents) get 2-allyl group-2,3-dimethyl 4-(4 '-chloro-phenyl-)-3 (E)-butenoic acid ethyl 0.0879 gram, productive rate is 71%.Product is a colourless liquid.
1H?NMR(300MHz，CDCl
3)δ7.33-7.26(m，2H)，7.17-7.14(m，2H)，6.33(s，1H)，5.77-5.62(m，1H)，5.14-5.04(m，2H)，4.16(q，J＝7.1Hz，2H)，2.66-2.50(m，2H)，1.77(d，J＝1.2Hz，3H)，1.36(s，3H)，1.25(t，J＝7.1Hz，3H)；
13C?NMR(CDCl
3，75MHz)δ175.6，140.1，136.5，133.9，132.0，130.3，128.1，124.3，118.1，60.7，52.2，40.8，21.4，15.7，14.2；MS(ESI，m/z)317.0((M(
37Cl)+Na
+)，40.83)，315.0((M(
35Cl)+Na
+)，100)；IR(neat，cm
-1)2980，2938，1731，1641，1593，?1490，1232，1092.HRMS?calcd?for?C
17H
21O
2ClNa
+(M(
35Cl)+Na
+)315.1122，found?315.1114.
Embodiment 4
Press embodiment 1 described method, different is that used substrate and reagent are: acetyl acetone iron (0.0067 gram, 0.02 mmole), 2-methyl-4-(4 '-bromophenyl)-2,3-divinyl acetoacetic ester (0.1132 gram, 0.4 mmole), (0.4 milliliter of the tetrahydrofuran solution of methylmagnesium-chloride, 3 equivalents, 3M), cuprous iodide (0.0073 gram, 0.04 mmole) and allyl bromide 98 are (0.17 milliliter, the d=1.39 grams per milliliter, 0.2420 the gram, 2 mmoles, 5 equivalents) 2-allyl group-2,3-dimethyl-4-(4 '-bromophenyl)-3 (E)-butenoic acid ethyl 0.0886 gram, productive rate is 65%.Product is a colourless liquid.
1H?NMR(300MHz，CDCl
3)δ7.47-7.41(m，2H)，7.12-7.08(m，2H)，6.31(s，1H)，5.77-5.61(m，1H)，5.14-5.04(m，2H)，4.16(q，J＝7.1Hz，2H)，2.66-2.50(m，2H)，1.77(d，J＝1.2Hz，3H)，1.36(s，3H)，1.25(t，J＝7.1Hz，3H)；
13C?NMR(CDCl
3，75MHz)δ175.5，140.2，137.0，133.9，131.1，130.7，124.3，120.1，118.1，60.7，52.2，40.7，21.4，15.7，14.2；MS(ESI，m/z)699((2×M(
81Br)+Na
+)，6.13)，696.6((2×M(
81Br?and?
79Br)+Na
+)，10.97)，695((2×M(
79Br)+Na
+)，5.81)，360.9((M(
81Br)+Na
+)，100)，358.9((M(
79Br)+Na
+)，98.71)；IR(neat，cm
-1)2979，1731，1641，1587，1487，1231，1140，1101，1010.HRMS?calcd?for?C
17H
21O
2BrNa
+(M(
19Br)+Na
+)359.0617，found?359.0605.
Embodiment 5
Press embodiment 1 described method, different is that used substrate and reagent are: acetyl acetone iron (0.0074 gram, 0.02 mmole), 2-methyl-4-(4 '-p-methoxy-phenyl)-2,3-divinyl acetoacetic ester (0.0912 gram, 0.4 mmole), (0.4 milliliter of the tetrahydrofuran solution of methylmagnesium-chloride, 3 equivalents, 3M), cuprous iodide (0.0074 gram, 0.04 mmole) and allyl bromide 98 are (0.17 milliliter, the d=1.39 grams per milliliter, 0.2420 the gram, 2 mmoles, 5 equivalents) 2-allyl group-2,3-dimethyl-4-(4 '-p-methoxy-phenyl)-3 (E)-butenoic acid ethyl 0.0594 gram, productive rate is 53%.Product is a colourless liquid.
Liquid；
1H?NMR(300MHz，CDCl
3)δ7.20-7.16(m，2H)，6.89-6.84(m，2H)，6.33(s，1H)，5.78-5.62(m，1H)，5.14-5.02(m，2H)，4.16(q，J＝7.2Hz，2H)，3.80(s，3H)，2.66-2.50(m，2H)，1.80(d，J＝1.2Hz，3H)，1.36(s，3H)，1.24(t，J＝7.2Hz，3H)；
13C?NMR(CDCl
3，75MHz)δ175.8，157.9，137.8，134.2，130.6，130.2，124.8，117.9，113.4，60.6，55.2，52.1，40.8，21.4，15.7，14.2；MS(ESI，m/z)311.0((M+Na
+)，100)；IR(neat，cm
-1)2979，1728，1641，1608，1575，1511，1250，1178，1140，1101，1036.HRMS?calcd?for?C
18H
24O
3Na
+(M+Na
+)311.1618，found?311.1617.
Embodiment 6
Press embodiment 1 described method, different is that used substrate and reagent are: acetyl acetone iron (0.0070 gram, 0.02 mmole), 2-methyl-4-phenyl-2,3-divinyl acetoacetic ester (0.0809 gram, 0.4 mmole), the tetrahydrofuran solution of methylmagnesium-chloride (0.4 milliliter, 3 equivalents, 3M), cuprous iodide (0.0072 gram, 0.04 mmole) and 2-phenyl allyl bromide 98 (0.3940 gram, 2 mmoles, 5 equivalents) 2-(2 '-phenyl allyl group)-2,3-dimethyl-4-phenyl-3 (E)-butenoic acid ethyl 0.0770 gram, productive rate is 58%.Product is a colourless liquid.
1H?NMR(300MHz，CDCl
3)δ7.35-7.15(m，8H)，7.08-7.02(m，2H)，6.32(s，1H)，5.24(d，J＝1.8Hz，1H)，5.12-5.08(m，1H)，3.98(dq，J
1＝10.5Hz，J
2＝7.2Hz，1H)，3.85(dq，J
1＝10.5Hz，J
2＝7.2Hz，1H)，3.16(dd，J
1＝13.5Hz，J
2＝0.5Hz，1H)，3.07(d，J＝13.5Hz，1H)，1.67(d，J＝0.9Hz，3H)，1.28(s，3H)，1.16(t，J＝7.2Hz，3H)；
13C?NMR(CDCl
3，75MHz)δ175.7，145.9，142.9，139.1，138.1，129.0，128.0，127.8，127.0，126.8，126.1，125.5，117.9，60.5，52.6，41.1，21.8，?16.0，14.0；MS(ESI，m/z)357((M+Na
+)，100)；IR(neat，cm
-1)2979，1727，1624，1599，1444，1231，1099.HRMS?calcd?for?C
23H
26O
2Na
+(M+Na
+)357.1830，found?357.1820.
Embodiment 7
Press embodiment 1 described method, different is that used substrate and reagent are: acetyl acetone iron (0.0067 gram, 0.02 mmole), 2-propyl group-4-phenyl-2,3-divinyl acetoacetic ester (0.0951 gram, 0.4 mmole), (0.4 milliliter of the tetrahydrofuran solution of methylmagnesium-chloride, 3 equivalents, 3M), cuprous iodide (0.0073 gram, 0.04 mmole) and 2-phenyl allyl bromide 98 (0.4001 the gram, 2 mmoles, 5 equivalents) get 2-(2 '-phenyl allyl group)-2-propyl group-3-methyl-4-phenyl-3 (E)-butenoic acid ethyl 0.0581 gram, productive rate is 39%.Product is a colourless liquid.
1H?NMR(300MHz，CDCl
3)δ7.35-7.14(m，8H)，7.11-7.07(m，2H)，6.31(s，1H)，5.21(d，J＝1.8Hz，1H)，5.07-5.04(m，1H)，3.97(dq，J
1＝10.5Hz，J
2＝7.2Hz，1H)，3.82(dq，J
1＝10.5Hz，J
2＝7.2Hz，1H)，3.14(d，J＝13.8Hz，1H)，3.04(d，J＝13.8Hz，1H)，1.71-1.58(m，5H)，1.30-1.10(m，5H)，0.72(t，J＝7.4Hz，3H)；
13C?NMR(CDCl
3，75MHz)δ175.2，146.2，143.1，138.3，138.1，129.0，127.9，127.8，127.0，126.8，126.1，117.8，60.4，56.3，37.0，33.8，17.5，16.1，14.2，14.0；MS(ESI，m/z)385.0((M+Na
+)，41.10)，363.1((M
++1)，100)；IR(neat，cm
-1)2959，2872，1728，1625，1599，1444，1208.HRMS?calcd?for?C
25H
30O
2Na
+(M+Na
+)385.2143，found?385.2138.
Embodiment 8
Press embodiment 1 described method, different is that used substrate and reagent are: acetyl acetone iron (0.0075 gram, 0.02 mmole), 2-methyl-4-phenyl-2,3-divinyl acetoacetic ester (0.0829 gram, 0.4 mmole), the tetrahydrofuran solution of methylmagnesium-chloride (0.4 milliliter, 3 equivalents, 3M), cuprous iodide (0.0078 gram, 0.04 mmole) and 3 (E)-phenyl allyl bromide 98s (0.4011 gram, 2 mmoles, 5 equivalents) 2-(3 ' (E)-phenyl allyl group)-2,3-dimethyl-4-phenyl-3 (E)-butenoic acid ethyl 0.0535 gram, productive rate is 39%.Product is a colourless liquid.
1H?NMR(300MHz，CDCl
3)δ7.37-7.16(m，10H)，6.46(d，J＝15.6Hz，1H)，6.43(s，1H)，6.12(dt，J
1＝15.6Hz，J
2＝7.2Hz，1H)，4.24-4.12(m，2H)，2.82-2.65(m，2H)，1.84(d，J＝1.5Hz，3H)，1.42(s，3H)，1.26(t，J＝7.2Hz，3H)；
13C?NMR(CDCl
3，75MHz)δ175.8，139.2，138.1，137.4，133.1，129.0，128.5，128.0，127.1，126.3，126.1，125.9，125.5，60.7，52.6，40.0，21.7，15.7，14.2；MS(ESI，m/z)373.0((M+K
+)，14.53)，357.1((M+Na
+)，100)；IR(neat，cm
-1)2979，2937，1727，1644，1599，1576，1495，1447，1229，1099.HRMS?calcd?for?C
23H
26O
2Na
+(M+Na
+)357.1825，found?357.1814.
Claims (6)
1. the method for synthesizing trans-alpha-allyl group-beta, gamma-esters of unsaturated carboxylic acids 3, under the effect of catalyzer acetyl acetone iron, Grignard reagent R
3Addition reaction takes place and generates 1 in MgCl and 2,3-connection olefin(e) acid ester 1,3-conjugated diolefine magnesia salt 2, again under cuprous iodide catalysis with
React, obtain a series of high zone and the trans α-allyl group of stereoselectivity-beta, gamma-esters of unsaturated carboxylic acids 3; Reaction formula is as follows:
R
1Be aryl; R
2And R
3Be alkyl; R
4And R
5Be hydrogen or phenyl; Wherein alkyl is C
nH
2n+1, n=1-9 in the formula; Aryl is phenyl and contains substituent phenyl, the steps include:
(1) in reaction flask, add catalyzer acetyl acetone iron, raw material 2,3-connection olefin(e) acid ester 1 and reaction solvent toluene, described acetyl acetone iron and 2, the equivalence ratio of 3-connection olefin(e) acid ester 1 is 0.005～0.05: 1; Described 2, the amount ratio of 3-connection olefin(e) acid ester 1 and reaction solvent toluene is 0.4 mmole: 5 milliliters; Nitrogen protection is stirred down, is cooled to subzero 78 degree, presses Grignard reagent R
3MgCl and 2, the equivalence ratio of 3-connection olefin(e) acid ester 1 is 1.2～3: 1, drips and contains Grignard reagent R
3The tetrahydrofuran solution of MgCl, reaction is 1 hour under subzero 78 degree, generates intermediate 2;
(2) after step (1) reacts completely, reaction system is risen to room temperature, in reaction flask, add again cuprous iodide and
Described cuprous iodide and 2, the equivalence ratio of 3-connection olefin(e) acid ester 1 is 0.10～0.20: 1; Described
With 2, the equivalence ratio of 3-connection olefin(e) acid ester 1 is 5～8: 1;
(3) after step (2) reacts completely, drip saturated ammonium chloride and stop, be back to room temperature and add entry again; Use extracted with diethyl ether, organic phase is used 1% hydrochloric acid successively, and saturated sodium bicarbonate, saturated aqueous common salt are respectively washed once, uses anhydrous sodium sulfate drying again, filters, and concentrates, and rapid column chromatography obtains trans α-allyl group-beta, gamma-esters of unsaturated carboxylic acids 3.
2. the method for synthesizing trans-alpha-allyl group according to claim 1-beta, gamma-esters of unsaturated carboxylic acids 3 is characterized in that Grignard reagent R
3MgCl and 2, the equivalence ratio of 3-connection olefin(e) acid ester 1 is 3: 1.
3. the method for synthesizing trans-alpha-allyl group according to claim 1-beta, gamma-esters of unsaturated carboxylic acids 3 is characterized in that acetyl acetone iron and 2, and the equivalence ratio of 3-connection olefin(e) acid ester 1 is 0.02: 1.
4. the method for synthesizing trans-alpha-allyl group according to claim 1-beta, gamma-esters of unsaturated carboxylic acids 3 is characterized in that cuprous iodide and 2, and the equivalence ratio of 3-connection olefin(e) acid ester 1 is 0.10: 1.
5. the method for synthesizing trans-alpha-allyl group according to claim 1-beta, gamma-esters of unsaturated carboxylic acids 3 is characterized in that
With 2, the equivalence ratio of 3-connection olefin(e) acid ester 1 is 5: 1.
6. the method for synthesizing trans-alpha-allyl group according to claim 1-beta, gamma-esters of unsaturated carboxylic acids 3 occurs in 2 with it is characterized in that reacting high regioselectivity, on two keys of the close carboxyl of 3-connection olefin(e) acid ester 1, and Grignard reagent R
3The R of MgCl
3Group be introduced in the connection alkene middle carbon on highly-solid selectively ground with the reservation two keys on R
1Be in cis-position, allyl group is introduced in connection alkene near on the carbon of carboxyl.
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| Zhan Lu et al.Iron-Catalyzed Highly Regio- and Stereoselective Conjugate Addition of 2,3-allenoates with Grignard Reagents.<J.AM.CHEM.SOC>.2007,第129卷(第47期),14546-14547. |
| Zhan Lu et al.Iron-Catalyzed Highly Regio-and Stereoselective Conjugate Addition of 2,3-allenoates with Grignard Reagents.<J.AM.CHEM.SOC>.2007,第129卷(第47期),14546-14547. * |
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