CN113024341B - A method for regio- and stereoselective synthesis of (E,E)-1,4,4-trisubstituted conjugated dienes - Google Patents

Abstract

The invention discloses a method for regio- and stereoselectively synthesizing (E,E)-1,4,4-trisubstituted conjugated dienes. The method comprises: preparing vinylcyclopropane with CoCl in the presence of an activating reagent The combination of ₂ and Xantphos ligands is used as a catalyst, and the reaction is carried out in an organic solvent at 50-100° C. to obtain (E,E)-1,4,4-trisubstituted conjugated diene stereoselectively. The method of the invention can stereoselectively synthesize (E,E)-1,4,4-trisubstituted conjugated dienes, the used catalysts and raw materials are cheap and easily available, the operation is simple, and the reaction process does not require the participation of other external reagents, Atoms are economical and have very high industrial application prospects.

Description

A method for regio- and stereoselective synthesis of (E,E)-1,4,4-trisubstituted conjugated dienes

technical field

The invention relates to a method for synthesizing (E,E)-1,4,4-trisubstituted conjugated dienes, in particular to a regio- and stereoselective synthesis of (E,E)-1,4,4-triolefins Methods of Substituting Conjugated Diolefins.

Background technique

Conjugated dienes are the key structural units of many natural products and drug molecules. In addition, due to their strong reactivity, conjugated dienes have been continuously expanded in the fields of organic synthesis and polymer chemistry, and their application value is increasing day by day. Conjugated dienes can realize enantioselective and regioselective hydrogen functionalization reactions, metal-catalyzed hydrosilylation reactions, hydroboration reactions, and Diels-Alder (D-A) cycloaddition reactions. The synthetic applications of conjugated dienes are as follows:

For a long time, people have devoted themselves to the development of efficient regio- and stereoselective synthesis of conjugated dienes. So far, some classical methods for the synthesis of conjugated dienes have been developed, including transition metal-catalyzed cross-coupling reactions, metathesis reactions and the Wittig reaction, etc., as follows:

However, these methods generally require the use of expensive noble metal catalysts, toxic reagents, harsh reaction conditions, and multi-step processes, and at the same time generate a large amount of solid-liquid waste, with low atom economy and unfriendly environment. In addition, these methods generally synthesize less-substituted straight-chain conjugated dienes with poor regio- and stereoselectivity, and it is still difficult to synthesize multi-substituted conjugated dienes with high regio- and stereoselectivity.

SUMMARY OF THE INVENTION

The object of the present invention is to provide a method for the regio- and stereoselective synthesis of (E,E)-1,4,4-trisubstituted conjugated dienes, which enables the stereoselective synthesis of (E,E)-1 ,4,4-trisubstituted conjugated diene, the catalyst and raw material used are cheap and easily available, the operation is simple, the reaction process does not require the participation of other external reagents, the atom economy is good, and it has a very high industrial application prospect.

In order to achieve the above objects, the present invention provides a method for regio- and stereoselective synthesis of (E,E)-1,4,4-trisubstituted conjugated dienes, the method comprising:

The vinylcyclopropane whose structural formula is shown in A is reacted in an organic solvent at 50-100 ° C in the presence of an activating reagent, and the combination of CoCl ₂ and Xantphos ligand is used as a catalyst, and the structural formula is shown in B. (E,E)-1,4,4-trisubstituted conjugated dienes shown.

Wherein, the structural formula of the Xantphos ligand is as follows:

The structural _formula of the complex of the CoCl and Xantphos ligand is as follows:

Wherein, R ¹ and R ² are each independently selected from aromatic rings.

Wherein, the organic solvent is selected from toluene; the activation reagent is selected from any one or more of sodium triethylborohydride, lithium triethylborohydride and sodium tri-sec-butylborohydride.

x和y各自独立的选自C、N、O或S，n为1～4。Preferably, the R ¹ and R ² are each independently selected from unsubstituted or substituted phenyl, naphthyl, biphenyl or

Each of x and y is independently selected from C, N, O or S, and n is 1-4.

x和y各自独立的选自C、N、O或S，n为1～4。Preferably, the R ¹ is selected from phenyl, alkoxyphenyl, alkylthiophenyl, alkylphenyl, alkylaminophenyl, fluorophenyl, trifluoromethylphenyl, naphthyl, biphenyl phenyl or

Each of x and y is independently selected from C, N, O or S, and n is 1-4.

Preferably, said R ² is selected from phenyl, alkoxyphenyl, alkylthiophenyl, alkylphenyl, alkylaminophenyl, fluorophenyl, trifluoromethylphenyl or naphthyl.

Preferably, the alkoxyphenyl group is selected from C ₁ -C ₃ alkoxyphenyl group; the alkylthiophenyl group is selected from C ₁ -C ₃ alkylthiophenyl group; the alkyl phenyl group is selected from from C ₁ -C ₃ alkylphenyl; the alkylaminophenyl is selected from C ₁ -C ₃ alkylaminophenyl.

Preferably, the reaction time is 1-24 h.

Preferably, the reaction time is 1-12 h.

Preferably, the molar ratio of vinylcyclopropane, CoCl ₂ , Xantphos and the activating reagent is 1:0.005-0.05:0.005-0.05:0.015-0.15.

The method for regio- and stereoselective synthesis of (E,E)-1,4,4-trisubstituted conjugated dienes of the present invention has the following advantages:

The method of the invention uses an inexpensive cobalt catalyst, uses a simple and readily available vinylcyclopropane as a raw material, selects ring-opening isomerization of vinylcyclopropane, and is regulated by ligands to efficiently synthesize the corresponding (E, E)- 1,4,4-Tri-substituted conjugated dienes. Compared with the existing method, the catalyst and raw materials used in the present invention are cheap and easy to obtain, the operation is simple, the reaction process does not need the participation of other external reagents, the atom economy is 100%, and the invention has a very high industrial application prospect. In addition, the reaction does not require the addition of any other toxic transition metal (such as ruthenium, rhodium, palladium, etc.) salts, and has great practical application value in the pharmaceutical and food chemical industries.

Detailed ways

The technical solutions in the embodiments of the present invention will be described clearly and completely below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

Example 1

A method for regio- and stereoselective synthesis of (E,E)-1,4,4-trisubstituted conjugated dienes, the method is as follows:

At 25°C, CoCl ₂ (0.025 mmol), Xantphos ligand (0.025 mmol), compound 1A (0.5 mmol) and toluene (1 mL) were added to a dry reaction tube, and sodium triethylborohydride (0.075 mmol) was injected. ), and then the reaction was stirred at 50° C. for 12 h, and the compound 1B was obtained by column chromatography as a white solid with a yield of 99%.

The NMR characterization data of compound 1B are as follows:

¹ H NMR: (500 MHz, CDCl ₃ ) δ 7.44-7.52 (m, 4H), 7.31-7.38 (m, 4H), 7.16-7.29 (m, 3H), 6.63-6.70 (dd, J=23.0, 11.5 Hz, 2H), 2.28 (s, 3H).

Example 2

A method for regio- and stereoselective synthesis of (E,E)-1,4,4-tri-substituted conjugated diene, which is basically the same as that of Example 1, except that the compound 2A selected by vinylcyclopropane, the product Compound 2B was obtained as a white solid in 99% yield.

The NMR characterization data of compound 2B are as follows:

¹ H NMR: (500 MHz, CDCl ₃ ) δ 7.42-7.49 (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).

¹³ C NMR: (125.8 MHz, CDCl ₃ ) δ 156.8, 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 method for regio- and stereoselective synthesis of (E,E)-1,4,4-tri-substituted conjugated diene, which is basically the same as that of Example 1, except that the compound 3A selected by vinylcyclopropane, the product It is compound 3B, which is a colorless oily liquid with a yield of 99%.

The NMR characterization data of compound 3B are as follows:

¹ H NMR: (400MHz, CDCl ₃ ) δ 7.45(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).

¹³ C NMR: (125.8 MHz, CDCl ₃ ) δ 159.6, 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 method for regio- and stereoselective synthesis of (E,E)-1,4,4-tri-substituted conjugated diene, which is basically the same as that of Example 1, except that the compound 4A selected by vinylcyclopropane, the product It is compound 4B, which is a white solid, Mp is 126.7°C-127.2°C, and the yield is 99%.

The NMR characterization data of compound 4B are as follows:

¹ H NMR: (400 MHz, CDCl ₃ ) δ 7.40-7.50 (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).

¹³ C NMR: (125.8 MHz, CDCl3) δ 159.0, 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 method for regio- and stereoselective synthesis of (E, E)-1,4,4-tri-substituted conjugated diene is substantially the same as that of Example 1, except that the compound 5A selected by vinylcyclopropane, the product It is compound 5B, which is a white solid, Mp is 84.5°C-85.2°C, and the yield is 99%.

The NMR characterization data of compound 5B are as follows:

¹ H NMR: (500 MHz, CDCl ₃ ) δ 7.46 (d, J=8.0 Hz, 2H), 7.40 (d, J=8.5 Hz, 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).

¹³ C NMR: (125.8 MHz, CDCl ₃ ) δ 140.1, 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 method for regio- and stereoselective synthesis of (E,E)-1,4,4-tri-substituted conjugated diene, which is basically the same as that of Example 1, except that the compound 6A selected by vinylcyclopropane, the product Compound 6B was obtained as a white solid in 99% yield.

The NMR characterization data of compound 6B are as follows:

¹ H NMR: (400.0 MHz, CDCl ₃ ) δ 7.43-7.48 (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 method for regio- and stereoselective synthesis of (E, E)-1,4,4-tri-substituted conjugated diene, which is basically the same as that of Example 1, except that the compound 7A selected by vinylcyclopropane, the product It is compound 7B, which is a yellow solid, Mp is 149.4°C-150.1°C, and the yield is 99%.

The NMR characterization data of compound 7B are as follows:

¹ H NMR: (500.0 MHz, CDCl ₃ ) δ 7.40-7.46 (m, 4H), 7.29-7.34 (t, 2H), 7.16-7.25 (m, 2H), 6.71 (d, J=9.0 Hz, 2H ), 6.57-6.63(m, 2H), 2.97(s, 6H), 2.24(s, 3H).

¹³ C NMR: (125.8 MHz, CDCl ₃ ) δ 149.8, 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 method for regio- and stereoselective synthesis of (E,E)-1,4,4-tri-substituted conjugated diene, which is basically the same as that of Example 1, except that the compound 8A selected by vinylcyclopropane, the product It is compound 8B, which is a white solid, Mp is 96.3°C-98.4°C, and the yield is 99%.

The NMR characterization data of compound 8B are as follows:

¹ H NMR: (500.0 MHz, CDCl ₃ ) δ 7.41-7.47 (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, 11.0 Hz, 2H), 2.24 (s, 3H).

¹³ C NMR: (125.8 MHz, CDCl ₃ ) δ 163.1, 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 method for regio- and stereoselective synthesis of (E,E)-1,4,4-tri-substituted conjugated diene, which is basically the same as that of Example 1, except that the compound 9A selected by vinylcyclopropane, the product It is compound 9B, which is a white solid, Mp is 178.9°C-181.1°C, and the yield is 99%.

The NMR characterization data of compound 9B are as follows:

¹ H NMR: (500.0 MHz, CDCl ₃ ) δ 7.54-7.70 (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).

¹³ C NMR: (125.8 MHz, CDCl ₃ ) δ 141.8, 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 method for regio- and stereoselective synthesis of (E, E)-1,4,4-tri-substituted conjugated diene, which is basically the same as that of Example 1, except that the compound 10A selected by vinylcyclopropane, the product It is compound 10B, which is a white solid, Mp is 140.7°C-142.7°C, and the yield is 99%.

The NMR characterization data of compound 10B are as follows:

¹ H NMR: (500.0 MHz, CDCl ₃ ) δ 7.89 (s, 1H), 7.77-7.86 (m, 3H), 7.69 (dd, J=8.5, 2.0 Hz, 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) .

¹³ C NMR: (125.8 MHz, CDCl ₃ ) δ 140.1, 137.7, 136.5, 133.5, 133.1, 132.7, 128.6, 128.2, 127.9, 127.8, 127.5, 127.5, 1226.4, 126.2, 125.8, 125.8, 124.9, 123.

Example 11

A method for regio- and stereoselective synthesis of (E,E)-1,4,4-tri-substituted conjugated diene is basically the same as that of Example 1, except that the compound 11A selected by vinylcyclopropane, the product It is compound 11B, compound 11B is a white solid, Mp is 80.0°C-80.2°C, and the yield is 99%.

The NMR characterization data of compound 11B are as follows:

¹ H NMR: (500.0 MHz, CDCl ₃ ) δ 7.95-8.01 (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) .

¹³ C NMR: (125.8 MHz, CDCl ₃ ) δ 143.4, 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

Example 12

A method for regio- and stereoselective synthesis of (E,E)-1,4,4-tri-substituted conjugated dienes, which is basically the same as that of Example 1, except that the compound 12A selected by vinylcyclopropane, the product It is compound 12B, which is a white solid, Mp is 122.8°C-123.2°C, and the yield is 99%.

The NMR characterization data of compound 12B are as follows:

¹ H NMR: (500.0 MHz, CDCl ₃ ) δ 7.55-7.62 (t, 4H), 7.47 (d, J=7.5 Hz, 2H), 7.32-7.38 (t, 2H), 7.24-7.29 (t, 1H) ), 7.19 (dd, J=15.5, 11.0 Hz, 1H), 6.63-6.77 (t, 2H), 2.28 (s, 3H).

¹³ C NMR: (125.8 MHz, CDCl ₃ ) δ 146.5, 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 method for regio- and stereoselective synthesis of (E,E)-1,4,4-tri-substituted conjugated diene, which is basically the same as that of Example 1, except that the compound 13A selected by vinylcyclopropane, the product It is compound 13B, which is a white solid, Mp is 100.6°C-100.9°C, and the yield is 99%.

The NMR characterization data of compound 13B are as follows:

¹ H NMR: (500.0 MHz, CDCl ₃ ) δ 7.45 (d, J=8.0 Hz, 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 ).

¹³ C NMR: (125.8 MHz, CDCl ₃ ) δ 147.8, 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 method for regio- and stereoselective synthesis of (E, E)-1,4,4-tri-substituted conjugated diene is basically the same as that of Example 1, except that the compound 14A selected by vinylcyclopropane, the product It is compound 14B, which is a colorless oily liquid with a yield of 99%.

The NMR characterization data of compound 14B are as follows:

¹ H NMR: (500.1 MHz, CDCl ₃ ) δ 7.58 (dd, J=8.0, 2.0 Hz, 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).

¹³ C NMR: (125.8 MHz, CDCl ₃ ) δ 156.7, 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 method for regio- and stereoselective synthesis of (E,E)-1,4,4-tri-substituted conjugated diene, which is basically the same as that of Example 1, except that the compound 15A selected by vinylcyclopropane, the product Compound 15B was obtained as a white solid in 99% yield.

The NMR characterization data of compound 15B are as follows:

¹ H NMR: (500.1 MHz, CDCl ₃ ) δ 7.50 (d, J=7.5 Hz, 2H), 7.33-7.38 (t, 2H), 7.15-7.29 (m, 3H), 7.07 (d, J=8.0 Hz, 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).

¹³ C NMR: (125.8 MHz, CDCl ₃ ) δ 159.7, 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 method for regio- and stereoselective synthesis of (E,E)-1,4,4-tri-substituted conjugated diene, which is basically the same as that of Example 1, except that the compound 16A selected by vinylcyclopropane, the product Compound 16B was obtained as a white solid in 99% yield.

The NMR characterization data of compound 16B are as follows:

¹ H NMR: (500.1 MHz, CDCl ₃ ) δ 7.46-7.51 (m, 2H), 7.40 (d, J=8.5 Hz, 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) .

¹³ C NMR: (125.8 MHz, CDCl ₃ ) δ 159.2, 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 method for regio- and stereoselective synthesis of (E,E)-1,4,4-trisubstituted conjugated dienes, which is basically the same as that of Example 1, except that the compound 17A selected by vinylcyclopropane, the product It is compound 17B, compound 17B is a white solid, Mp is 104.6°C-106.7°C, and the yield is 99%.

The NMR characterization data of compound 17B are as follows:

¹ H NMR: (500.1 MHz, CDCl ₃ ) δ 7.49 (d, J=8.0 Hz, 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).

¹³ C NMR: (125.8 MHz, CDCl ₃ ) δ 143.1, 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 method for regio- and stereoselective synthesis of (E,E)-1,4,4-trisubstituted conjugated dienes, which is basically the same as that of Example 1, except that the compound 18A selected by vinylcyclopropane, the product Compound 18B was obtained as a white solid in 99% yield.

The NMR characterization data of compound 18B are as follows:

¹ H NMR: (500.1 MHz, CDCl ₃ ) δ 7.73-7.83 (m, 4H), 7.68 (d, J=8.5 Hz, 1H), 7.51 (d, J=8.0 Hz, 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).

¹³ C NMR: (125.8MHz, CDCl ₃ ) δ 143.0, 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 , 16.2.

Example 19

A method for regio- and stereoselective synthesis of (E,E)-1,4,4-tri-substituted conjugated diene is basically the same as that of Example 1, except that the compound 19A selected by vinylcyclopropane, the product Compound 19B was obtained as a white solid in 99% yield.

The NMR characterization data of compound 19B are as follows:

¹ H NMR: (500.1 MHz, CDCl ₃ ) δ 7.50 (d, J=8.0 Hz, 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).

¹³ C NMR: (125.8 MHz, CDCl ₃ ) δ 151.6, 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 method for regio- and stereoselective synthesis of (E,E)-1,4,4-tri-substituted conjugated diene is substantially the same as that of Example 1, except that the compound 20A selected by vinylcyclopropane, the product Compound 20B was obtained as a white solid in 99% yield.

The NMR characterization data of compound 20B are as follows:

¹ H NMR: (500.1 MHz, CDCl ₃ ) δ 7.43-7.61 (m, 6H), 7.31-7.39 (t, 2H), 7.20-7.30 (m, 2H), 6.58-6.71 (m, 2H), 2.30 (s, 3H).

¹³ C NMR: (125.8 MHz, CDCl ₃ ) δ 142.7, 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 method for regio- and stereoselective synthesis of (E,E)-1,4,4-tri-substituted conjugated diene is basically the same as that of Example 1, except that the compound 21A selected by vinylcyclopropane, the product It is compound 21B, compound 21B is a white solid, Mp is 105.2°C-105.5°C, and the yield is 99%.

The NMR characterization data of compound 21B are as follows:

¹ H NMR: (500.1 MHz, CDCl ₃ ) δ 7.45-7.55 (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).

¹³ C NMR: (125.8 MHz, CDCl ₃ ) δ 163.2, 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.

Examples 22-23

A method for regio- and stereoselective synthesis of (E,E)-1,4,4-trisubstituted conjugated dienes is basically the same as that of Example 1, except that the reaction times of Examples 22-23 are respectively The yields of the reaction were 73% and 93% for 1 h and 3 h, respectively.

Examples 24-25

A method for regio- and stereoselective synthesis of (E,E)-1,4,4-trisubstituted conjugated dienes is basically the same as that of Example 1, except that the activating reagents used in Examples 24-25 are respectively were lithium triethylborohydride (LiBHEt ₃ ) and sodium tri-sec-butylborohydride (NaBHsBu ₃ ), with yields of 82% and 84%, respectively.

Example 26

A method for regio- and stereoselective synthesis of (E,E)-1,4,4-trisubstituted conjugated dienes is basically the same as that in Example 1, except that the amount of CoCl ₂ is 0.05 mmol, and Xantphos The amount of the compound was 0.05 mmol, the amount of compound 1A was 10 mmol, the amount of toluene was 10 mL, the amount of sodium triethylborohydride was 0.15 mmol, and the yield of compound 1B was 99%.

Example 27

A method for regio- and stereoselective synthesis of (E,E)-1,4,4-tri-substituted conjugated dienes, which is basically the same as that of Example 1, except that: the complexation of CoCl ₂ and Xantphos ligands Compound 1B was used as the catalyst, and the yield of compound 1B was 99%.

Comparative Examples 1-4

Basically the same as Example 1, the difference is: the reaction temperatures of Comparative Examples 1-4 are room temperature, the reaction solvents are toluene, THF, dioxane and n-hexane, respectively, and the yields are 70%, 19%, 35%, respectively. % and 15%.

Comparative Examples 5-7

Basically the same as Example 1, the difference is: the reaction temperature of Comparative Examples 5-7 is room temperature, the reaction solvent is toluene, the ligands are respectively dppe, DPEphos, Xnatphos, and the metal salts are respectively CoCl ₂ , CoCl ₂ and FeCl ₂ , no response.

Comparative Example 8

It is basically the same as that in Example 1, except that the compound 22A selected by vinylcyclopropane is the compound 22B, and the yield of the compound 22B is 11%.

Comparative Example 9

It is basically the same as Example 1, except that the compound 23A selected for vinylcyclopropane is unreacted.

While the content of the present invention has been described in detail by way of the above preferred embodiments, it should be appreciated that the above description should not be construed as limiting the present invention. Various modifications and alternatives to the present invention will be apparent to those skilled in the art upon reading the foregoing. Accordingly, the scope of protection of the present invention should be defined by the appended 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.