CN113024341B - Method for regio-and stereoselectively synthesizing (E, E) -1,4, 4-trisubstituted conjugated diene - Google Patents
Method for regio-and stereoselectively synthesizing (E, E) -1,4, 4-trisubstituted conjugated diene Download PDFInfo
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Abstract
The invention discloses a method for regioselectively synthesizing (E, E) -1,4, 4-trisubstituted conjugated diene, which comprises the following steps: vinylcyclopropane in the presence of an activating reagent and CoCl2And a Xantphos ligand as a catalyst, reacting in an organic solvent at 50-100 ℃, and stereoselectively obtaining the (E, E) -1,4, 4-trisubstituted conjugated diene. The method can stereoselectively synthesize the (E, E) -1,4, 4-trisubstituted conjugated diene, the used catalyst and raw materials are cheap and easy to obtain, the operation is simple and convenient, the reaction process does not need the participation of other additional reagents, the atom economy is good, and the method has very high industrial application prospect.
Description
Technical Field
The invention relates to a method for synthesizing (E, E) -1,4, 4-trisubstituted conjugated diene, in particular to a method for synthesizing (E, E) -1,4, 4-trisubstituted conjugated diene regioselectively and stereoselectively.
Background
Conjugated diene is a key structural unit of a plurality of natural products and drug molecules, and in addition, because conjugated diene has stronger reactivity, the application range of the conjugated diene in the fields of organic synthesis, polymer chemistry and the like is continuously expanded, and the application value of the conjugated diene is increased day by day. The conjugated diene can realize the hydrogen functionalization reaction with the enantioselectivity and the regioselectivity, the hydrosilation reaction catalyzed by metal, the hydroboration reaction, the Diels-Alder (D-A) cyclic addition reaction and the like, and the synthesis of the conjugated diene is applied as follows:
for a long time, efforts have been made to develop efficient methods for regio-and stereoselective synthesis of conjugated diolefins, and some classical methods for synthesizing conjugated diolefins have been developed so far, including transition metal catalyzed cross-coupling reactions, metathesis reactions, Wittig reactions, etc., as shown below:
however, these methods generally require the use of expensive noble metal catalysts, toxic reagents, harsh reaction conditions and multi-step processes, and also generate a large amount of solid-liquid waste, and are low in atom economy and environmentally unfriendly. In addition, these processes generally synthesize less substituted, linear conjugated diolefins, which are less regio-and stereoselective and have greater difficulties in synthesizing highly regio-and stereoselective polysubstituted conjugated diolefins.
Disclosure of Invention
The invention aims to provide a method for regioselectively and stereoselectively synthesizing (E, E) -1,4, 4-trisubstituted conjugated diene, which can stereoselectively synthesize the (E, E) -1,4, 4-trisubstituted conjugated diene, has the advantages of cheap and easily obtained catalyst and raw materials, simple and convenient operation, no need of participation of other additional reagents in the reaction process, good atom economy and very high industrial application prospect.
In order to achieve the above objects, the present invention provides a process for regio-and stereoselective synthesis of (E, E) -1,4, 4-trisubstituted conjugated diene, the process comprising:
in the presence of an activating reagent, adding CoCl into vinyl cyclopropane with a structural formula shown as A2And a Xantphos ligand as a catalyst, reacting in an organic solvent at 50-100 ℃, and stereoselectively obtaining the (E, E) -1,4, 4-trisubstituted conjugated diene with the structural formula shown as B.
Wherein the structure of the Xantphos ligand is as follows:
the CoCl2The formula of the complex with xanthphos ligand is as follows:
wherein R is1、R2Each independently selected from aromatic rings.
Wherein the organic solvent is selected from toluene; the activating reagent is selected from any one or more than two of sodium triethylborohydride, lithium triethylborohydride and sodium tri-sec-butylborohydride.
Preferably, said R is1、R2Each independently selected from unsubstituted or substituted phenyl, naphthyl, biphenyl or
x and y are respectively and independently selected from C, N, O or S, and n is 1-4.
Preferably, said R is1Selected from phenyl, alkoxyphenyl, alkylthiophenyl, alkylphenyl, alkylaminophenyl, fluorophenyl, trifluoromethylphenyl, naphthyl, biphenyl or
x and y are respectively and independently selected from C, N, O or S, and n is 1-4.
Preferably, said R is2Selected from phenyl, alkoxyphenyl, alkylthiophenyl, alkylphenyl, alkylaminophenyl, fluorophenyl, trifluoromethylphenyl or naphthyl.
Preferably, the alkoxyphenyl is selected from C1～C3An alkoxyphenyl group; said alkylthiophenyl is selected from C1～C3An alkylthio phenyl group; the alkyl phenyl is selected from C1～C3An alkyl phenyl group; the alkyl amino phenyl is selected from C1～C3An alkylamino phenyl group.
Preferably, the reaction time is 1-24 h.
Preferably, the reaction time is 1-12 h.
Preferably, the vinylcyclopropane, CoCl2Xanthphos, activating reagent in a molar ratio of 1: 0.005-0.05: 0.005-0.05: 0.015 to 0.15.
The method for regioselectively synthesizing (E, E) -1,4, 4-trisubstituted conjugated diene has the following advantages:
the method uses a cheap cobalt catalyst, takes simple and easily-obtained vinylcyclopropane as a raw material, selectively performs ring opening isomerization on the vinylcyclopropane, and efficiently synthesizes the corresponding (E, E) -1,4, 4-trisubstituted conjugated diene through ligand regulation. Compared with the prior art, the method has the advantages of cheap and easily obtained catalyst and raw materials, simple and convenient operation, no need of participation of other additional reagents in the reaction process, 100% atomic economy and very high industrial application prospect. In addition, the reaction does not need to add any other toxic transition metal (such as ruthenium, rhodium, palladium and the like) salts, and has great practical application value in the pharmaceutical and food chemical industries.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
A method for regio-and stereoselectively synthesizing (E, E) -1,4, 4-trisubstituted conjugated diene comprises the following steps:
adding CoCl into a dry reaction tube at 25 deg.C2(0.025mmol), Xantphos ligand (0.025mmol), Compound 1A (0.5mmol) and toluene (1mL) were injected with sodium triethylborohydride (0.075mmol) and the reaction stirred at 50 ℃ for 12h before column chromatography gave Compound 1B as a white solid in 99% yield.
The nuclear magnetic characterization data for compound 1B is as follows:
1H NMR:(500MHz,CDCl3)δ7.44-7.52(m,4H),7.31-7.38(m,4H),7.16-7.29(m,3H),6.63-6.70(dd,J＝23.0,11.5Hz,2H),2.28(s,3H)。
example 2
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: the vinyl cyclopropane selected compound 2A, the product was compound 2B, compound 2B was a white solid, and the yield was 99%.
Nuclear magnetic characterization data for compound 2B are as follows:
1H NMR:(500MHz,CDCl3)δ7.42-7.49(m,2H),7.29-7.36(m,2H),7.13-7.29(m,4H),6.92-6.98(m,1H),6.90(d,J＝8.0Hz,1H),6.58(d,J＝15.5Hz,1H),6.33(dd,J＝11.0,1.0Hz,1H),3.84(s,3H),2.23(s,3H)。
13C NMR:(125.8MHz,CDCl3)δ156.8,137.9,137.6,134.2,132.2,129.4,129.3,128.6,128.2,127.2,126.3,125.6,120.6,110.9,55.4,17.7。
example 3
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: the vinyl cyclopropane adopts the compound 3A, the product is the compound 3B, the compound 3B is colorless oily liquid, and the yield is 99 percent.
Nuclear magnetic characterization data for compound 3B are as follows:
1H NMR:(400MHz,CDCl3)δ7.45(d,2H),7.30-7.38(m,2H),7.14-7.29(m,3H),7.06-7.16(m,1H),7.03(s,1H),7.79-7.86(d,1H),7.61-7.72(t,2H),3.84(s,3H),2.27(s,3H)。
13C NMR:(125.8MHz,CDCl3)δ159.6,144.5,137.7,136.6,133.0,129.2,128.6,127.5,127.4,126.3,125.7,118.2,112.4,111.5,55.2,16.2。
example 4
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: the product of the compound 4A selected from the vinyl cyclopropane is a compound 4B, the compound 4B is a white solid, the Mp is 126.7-127.2 ℃, and the yield is 99%.
Nuclear magnetic characterization data for compound 4B are as follows:
1H NMR:(400MHz,CDCl3)δ7.40-7.50(m,4H),7.29-7.37(m,2H),7.14-7.25(m,2H),6.86-6.93(m,2H),6.55-6.69(m,2H),2.25(t,3H),1.54(s,3H)。
13C NMR:(125.8MHz,CDCl3)δ159.0,138.0,136.3,132.1,128.7,127.3,126.7,126.3,126.0,125.8,113.8,55.3,16.2。
example 5
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: the vinyl cyclopropane adopts the compound 5A, the product is the compound 5B, the compound 5B is a white solid, the Mp is 84.5-85.2 ℃, and the yield is 99%.
Nuclear magnetic characterization data for compound 5B are as follows:
1H NMR:(500MHz,CDCl3)δ7.46(d,J＝8.0Hz,2H),7.40(d,J＝8.5Hz,2H),7.30-7.36(t,2H),7.14-7.24(m,4H),6.61-6.68(m,2H),2.36(s,3H),2.26(s,3H)。
13C NMR:(125.8MHz,CDCl3)δ140.1,137.9,137.0,136.8,132.5,129.1,128.7,127.4,126.6,126.3,126.0,125.5,21.1,16.2。
example 6
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: the product of compound 6A selected from the vinylcyclopropane was compound 6B, and compound 6B was a white solid with a yield of 99%.
Nuclear magnetic characterization data for compound 6B are as follows:
1H NMR:(400.0MHz,CDCl3)δ7.43-7.48(m,3H),7.42(s,1H),7.30-7.36(t,2H),7.24(d,J＝8.8Hz,3H),7.16-7.21(m,1H),6.62-6.70(m,2H)。
example 7
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: the vinyl cyclopropane adopts the compound 7A, the product is the compound 7B, the compound 7B is a yellow solid, the Mp is 149.4-150.1 ℃, and the yield is 99%.
Nuclear magnetic characterization data for compound 7B are as follows:
1H NMR:(500.0MHz,CDCl3)δ7.40-7.46(m,4H),7.29-7.34(t,2H),7.16-7.25(m,2H),6.71(d,J＝9.0Hz,2H),6.57-6.63(m,2H),2.97(s,6H),2.24(s,3H)。
13C NMR:(125.8MHz,CDCl3)δ149.8,138.2,136.7,130.9,130.8,128.6,126.9,126.4,126.3,126.1,124.1,112.2,40.5,15.9。
example 8
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: the vinyl cyclopropane adopts the compound 8A, the product is the compound 8B, the compound 8B is a white solid, the Mp is 96.3-98.4 ℃, and the yield is 99%.
Nuclear magnetic characterization data for compound 8B are as follows:
1H NMR:(500.0MHz,CDCl3)δ7.41-7.47(m,4H),7.30-7.35(t,2H),7.13-7.25(m,2H),6.99-7.06(m,2H),6.57(dd,J＝15.0,11.0Hz,2H),2.24(s,3H)。
13C NMR:(125.8MHz,CDCl3)δ163.1,161.1,139.1,139.0,137.7,135.6,132.9,128.6,127.5,127.2,127.2,127.2,127.1,126.3,125.6,115.2,115.0,16.3。
example 9
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: the vinyl cyclopropane adopts the compound 9A, the product is the compound 9B, the compound 9B is a white solid, the Mp is 178.9-181.1 ℃, and the yield is 99%.
Nuclear magnetic characterization data for compound 9B are as follows:
1H NMR:(500.0MHz,CDCl3)δ7.54-7.70(m,6H),7.40-7.52(m,4H),7.30-7.38(t,3H),7.18-7.30(m,2H),6.64-6.78(t,2H),2.31(s,3H)。
13C NMR:(125.8MHz,CDCl3)δ141.8,140.7,139.9,137.7,136.2,133.0,128.8,128.6,127.4,127.3,127.2,127.0,126.9,126.4,126.0,125.8,16.1。
example 10
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: the vinyl cyclopropane adopts the compound 10A, the product is the compound 10B, the compound 10B is a white solid, the Mp is 140.7-142.7 ℃, and the yield is 99%.
Nuclear magnetic characterization data for compound 10B are as follows:
1H NMR:(500.0MHz,CDCl3)δ7.89(s,1H),7.77-7.86(m,3H),7.69(dd,J＝8.5,2.0Hz,1H),7.41-7.52(m,4H),7.31-7.37(t,2H),7.20-7.30(m,2H),6.82(d,J＝11.0Hz,1H),6.72(d,J＝15.0Hz,1H),2.35(s,3H)。
13C NMR:(125.8MHz,CDCl3)δ140.1,137.7,136.5,133.5,133.1,132.7,128.6,128.2,127.9,127.8,127.5,127.5,126.4,126.2,125.8,125.8,124.4,123.9,16.2。
example 11
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: the vinyl cyclopropane adopts the compound 11A, the product is the compound 11B, the compound 11B is a white solid, the Mp is 80.0-80.2 ℃, and the yield is 99%.
Nuclear magnetic characterization data for compound 11B are as follows:
1H NMR:(500.0MHz,CDCl3)δ7.95-8.01(m,1H),7.79-7.85(m,1H),7.72(d,J＝7.5Hz,1H),7.38-7.47(m,5H),7.28-7.33(m,3H),7.17-7.26(m,2H),6.55(d,J＝15.5Hz,1H),6.32(d,J＝11.0Hz,1H),2.32(s,3H)。
13C NMR:(125.8MHz,CDCl3)δ143.4,137.7,137.6,133.8,132.5,131.0,130.5,128.6,128.4,127.4,127.2,126.3,125.8,125.8,125.6,125.3,125.2,124.8,19.6。
example 12
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: the product of the compound 12A selected from the vinyl cyclopropane is a compound 12B, the compound 12B is a white solid, the Mp is 122.8-123.2 ℃, and the yield is 99%.
Nuclear magnetic characterization data for compound 12B are as follows:
1H NMR:(500.0MHz,CDCl3)δ7.55-7.62(t,4H),7.47(d,J＝7.5Hz,2H),7.32-7.38(t,2H),7.24-7.29(t,1H),7.19(dd,J＝15.5,11.0Hz,1H),6.63-6.77(t,2H),2.28(s,3H)。
13C NMR:(125.8MHz,CDCl3)δ146.5,137.4,135.2,134.3,129.1,128.8,128.7,127.8,126.5,125.8,125.4,125.3,125.2,123.2,16.1。
example 13
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: the product of the compound 13A selected from the vinyl cyclopropane is a compound 13B, the compound 13B is a white solid, the Mp is 100.6-100.9 ℃, and the yield is 99%.
Nuclear magnetic characterization data for compound 13B are as follows:
1H NMR:(500.0MHz,CDCl3)δ7.45(d,J＝8.0Hz,2H),7.29-7.37(t,2H),7.12-7.25(m,2H),7.95-7.03(m,2H),6.79(d,J＝8.0Hz,1H),6.64(d,J＝16.0Hz,1H),6.55(d,J＝11.0Hz,1H),5.96(s,2H),2.22(s,3H)。
13C NMR:(125.8MHz,CDCl3)δ147.8,146.8,137.8,137.4,136.3,132.4,128.6,127.3,126.3,126.3,125.8,119.3,108.0,106.0,101.0,16.4。
example 14
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: the vinyl cyclopropane selected compound 14A, the product was compound 14B, compound 14B was a colorless oily liquid, and the yield was 99%.
The nuclear magnetic characterization data for compound 14B is as follows:
1H NMR:(500.1MHz,CDCl3)δ7.58(dd,J＝8.0,2.0Hz,1H),7.47-7.51(m,2H),7.31-7.36(t,2H),7.18-7.26(m,3H),7.02(d,J＝16.0Hz,1H),6.92-6.97(t,1H),6.87(d,J＝8.5Hz,1H),6.69(d,J＝11.0Hz,1H),3.86(s,3H),2.26(s,3H)。
13C NMR:(125.8MHz,CDCl3)δ156.7,143.1,136.0,128.4,128.3,128.1,127.6,126.9,126.8,126.5,126.4,125.6,120.7,110.9,55.5,16.1。
example 15
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: the vinyl cyclopropane selected compound 15A, the product was compound 15B, compound 15B was a white solid, and the yield was 99%.
Nuclear magnetic characterization data for compound 15B are as follows:
1H NMR:(500.1MHz,CDCl3)δ7.50(d,J＝7.5Hz,2H),7.33-7.38(t,2H),7.15-7.29(m,3H),7.07(d,J＝8.0Hz,1H),6.99(s,1H),6.79(d,J＝8.0Hz,1H),6.64(d,J＝14.5Hz,2H),3.84(s,3H),2.28(s,3H)。
13C NMR:(125.8MHz,CDCl3)δ159.7,143.2,139.5,137.0,132.7,128.3,127.2,127.2,126.1,125.6,119.1,113.0,55.2,16.2。
example 16
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated dienes substantially as in example 1, except that: the vinyl cyclopropane selected compound 16A, the product was compound 16B, compound 16B was a white solid, and the yield was 99%.
Nuclear magnetic characterization data for compound 16B are as follows:
1H NMR:(500.1MHz,CDCl3)δ7.46-7.51(m,2H),7.40(d,J＝8.5Hz,2H),7.31-7.36(t,2H),7.22-7.27(m,1H),7.06(dd,J＝15.5,11.0Hz,1H),6.87(d,J＝8.5Hz,2H),6.59-6.65(m,2H),3.81(s,3H),2.26(s,3H)。
13C NMR:(125.8MHz,CDCl3)δ159.2,143.1,135.5,132.5,130.6,128.3,127.6,127.5,126.9,125.5,123.9,114.1,55.3,16.1。
example 17
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: the product of the compound 17A selected from the vinyl cyclopropane is a compound 17B, the compound 17B is a white solid, the Mp is 104.6-106.7 ℃, and the yield is 99%.
Nuclear magnetic characterization data for compound 17B are as follows:
1H NMR:(500.1MHz,CDCl3)δ7.49(d,J＝8.0Hz,2H),7.31-7.38(m,4H),7.21-7.27(m,1H),7.11-7.19(m,3H),6.64(d,J＝14.0Hz,2H),2.34(s,3H),2.26(s,3H)。
13C NMR:(125.8MHz,CDCl3)δ143.1,137.3,136.1,135.0,132.9,129.4,128.3,127.5,127.0,126.3,125.6,124.9,77.3,77.0,76.7,21.2,16.1。
example 18
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: the vinyl cyclopropane selected compound 18A, the product was compound 18B, compound 18B was a white solid, and the yield was 99%.
Nuclear magnetic characterization data for compound 18B are as follows:
1H NMR:(500.1MHz,CDCl3)δ7.73-7.83(m,4H),7.68(d,J＝8.5Hz,1H),7.51(d,J＝8.0Hz,2H),7.39-7.47(m,2H),7.24-7.38(m,4H),6.81(d,J＝15.5Hz,1H),6.70(d,J＝11.5Hz,1H),2.31(s,3H)。
13C NMR:(125.8MHz,CDCl3)δ143.0,137.0,135.3,133.7,133.0,128.3,128.2,127.9,127.7,127.4,127.2,126.3,126.2,126.1,125.8,125.6,123.5,77.3,77.0,76.7,16.2。
example 19
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: the product of compound 19A, which is selected from the vinylcyclopropane, is compound 19B, and compound 19B is a white solid with the yield of 99%.
Nuclear magnetic characterization data for compound 19B are as follows:
1H NMR:(500.1MHz,CDCl3)δ7.50(d,J＝8.0Hz,2H),7.30-7.37(t,2H),7.21-7.27(t,1H),7.03-7.12(m,2H),6.96(d,J＝15.5Hz,1H),6.69(d,J＝10.5Hz,1H),6.51(s,1H),3.91(s,6H),3.86(s,3H),2.27(s,3H)。
13C NMR:(125.8MHz,CDCl3)δ151.6,149.5,143.4,143.1,134.9,128.2,128.2,127.3,126.8,125.5,124.3,118.7,109.6,97.7,56.6,56.6,56.0,16.1。
example 20
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: the vinyl cyclopropane selected compound 20A, the product was compound 20B, compound 20B was a white solid, and the yield was 99%.
Nuclear magnetic characterization data for compound 20B are as follows:
1H NMR:(500.1MHz,CDCl3)δ7.43-7.61(m,6H),7.31-7.39(t,2H),7.20-7.30(m,2H),6.58-6.71(m,2H),2.30(s,3H)。
13C NMR:(125.8MHz,CDCl3)δ142.7,141.3,138.8,131.1,128.4,128.1,127.6,126.9,126.4,125.7,125.6,125.6,16.4。
example 21
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: the compound 21A selected as the vinyl cyclopropane is a compound 21B, the product is a white solid, the Mp is 105.2-105.5 ℃, and the yield is 99%.
Nuclear magnetic characterization data for compound 21B are as follows:
1H NMR:(500.1MHz,CDCl3)δ7.45-7.55(2.26,m,2H),7.29-7.45(2.26,m,4H),7.19-7.28(m,1H),7.05-7.16(m,1H),6.94-7.05(m,2H),6.54-6.69(m,2H),2.26(s,3H)。
13C NMR:(125.8MHz,CDCl3)δ163.2,161.2,142.9,136.8,133.9,133.9,131.5,128.3,127.8,127.7,127.2,127.1,125.6,125.5,125.5,115.7,115.5,16.2。
examples 22 to 23
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: the reaction times for examples 22-23 were 1h and 3h, respectively, and the yields were 73% and 93%, respectively.
Examples 24 to 25
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: examples 24-25 each use lithium triethylborohydride (LiBHEt)3) And tri-sec-butyl borohydrideSodium chloride (NaBHsBu)3) The yields were 82% and 84%, respectively.
Example 26
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: CoCl2The amount of (1) was 0.05mmol, the amount of Xantphos ligand was 0.05mmol, the amount of compound 1A was 10mmol, the amount of toluene was 10mL, the amount of triethylborohydride was 0.15mmol, and the yield of compound 1B was 99%.
Example 27
A regio-and stereoselective process for the synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, substantially as described in example 1, except that: with CoCl2And Xantphos ligand complex as catalyst, compound 1B yield 99%.
Comparative examples 1 to 4
Essentially the same as example 1, except that: the reaction temperatures of comparative examples 1 to 4 were all room temperature, and the reaction solvents were toluene, THF, dioxane and n-hexane, respectively, with yields of 70%, 19%, 35% and 15%, respectively.
Comparative examples 5 to 7
Essentially the same as example 1, except that: comparative examples 5 to 7 were all at room temperature, the reaction solvent was toluene, the ligands were dppe, DPEphos and Xnatphos, respectively, and the metal salts were CoCl, respectively2、CoCl2And FeCl2And is not reacted.
Comparative example 8
Essentially the same as example 1, except that: the vinyl cyclopropane is selected from a compound 22A, the product is a compound 22B, and the yield of the compound 22B is 11%.
Comparative example 9
Essentially the same as example 1, except that: the vinylcyclopropane selected from compound 23A, was not reacted.
While the present invention has been described in detail with reference to the preferred embodiments, it should be understood that the above description should not be taken as limiting the invention. Various modifications and alterations to this invention will become apparent to those skilled in the art upon reading the foregoing description. Accordingly, the scope of the invention should be determined from the following claims.
Claims (4)
1. A process for the regio-and stereoselective synthesis of (E, E) -1,4, 4-trisubstituted conjugated diolefins, characterized in that it comprises:
in the presence of an activating reagent, adding CoCl into vinyl cyclopropane with a structural formula shown as A2The composition of the (E, E) -1,4, 4-trisubstituted conjugated diene represented by the structural formula B is taken as a catalyst and reacts in an organic solvent at the temperature of 50-100 ℃ to obtain (E, E) -1,4, 4-trisubstituted conjugated diene in a stereoselective manner;
wherein the structure of the Xantphos ligand is as follows:
the CoCl2The formula of the complex with xanthphos ligand is as follows:
wherein, R is1Selected from phenyl, methoxyphenyl, methylthiophenyl, methylphenyl, methylaminophenyl, fluorophenyl, trifluoromethylphenyl, naphthyl, biphenyl or
x and y are each independently selected from O, n is 1;
wherein, R is2Selected from phenyl, methoxyphenyl, methylthiophenyl, methylphenyl, methylaminophenyl, fluorophenyl, trifluoromethylphenyl or naphthyl;
wherein the organic solvent is selected from toluene; the activating reagent is selected from any one or more than two of sodium triethylborohydride, lithium triethylborohydride and sodium tri-sec-butylborohydride.
2. The process for the regio-and stereoselective synthesis of (E, E) -1,4, 4-trisubstituted conjugated diene according to claim 1, characterized in that the reaction time is comprised between 1 and 24 h.
3. The process for the regio-and stereoselective synthesis of (E, E) -1,4, 4-trisubstituted conjugated diene according to claim 2, characterized in that the reaction time is comprised between 1 and 12 h.
4. A process for the regio-and stereoselective synthesis of (E, E) -1,4, 4-trisubstituted conjugated diene according to any of claims 1 to 3, characterized in that said vinylcyclopropane, CoCl2The molar ratio of the Xantphos ligand to the activating reagent is 1: 0.005-0.05: 0.005-0.05: 0.015 to 0.15.
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| Diazodiphenylmethane and Monosubstituted Butadienes: Kinetics and a New Chapter of Vinylcyclopropane Chemistry;Akihiro Ohta et al.;《Helvetica Chimica Acta》;20081231;第91卷(第5期);1980-1985页 * |
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