A method for preparing cyclopropene by using allyl boron compound and zinc catalysis

Abstract

The invention discloses an allyl boron compound and a zinc-catalyzed cyclopropene preparation method thereof, wherein a cyclopropene compound and a borane complex are used as raw materials, zinc chloride is used as a catalyst, and dichloromethane is used as a reaction solvent, and the allyl boron compound is obtained after reaction. The invention has the advantages of cheap and easy availability of catalyst, convenient reaction operation, high catalytic efficiency, mild reaction conditions, large-scale production, etc.

Description

Technical Field

[0001] The invention belongs to the technical field of fine chemical industry, and in particular relates to an allyl boron compound and a method for preparing cyclopropene catalyzed by zinc. Background Art

[0002] Allyl boron compounds are an important class of reactive intermediates, which are widely used in organic synthesis, materials chemistry and medicinal chemistry. Transition metal catalysis of cyclopropene compounds, with carbene intermediates inserted into borane, is the most direct, effective and atom-economical method for preparing such compounds. The best synthetic method currently is the copper catalytic system supported by phosphorus ligands, but such catalytic systems have the disadvantages of expensive ligands, low reactivity and poor applicability of reaction substrates. Therefore, it is of great research value to develop a new catalytic system that is cheap, readily available and has excellent performance. Summary of the invention

[0003] The purpose of the present invention is to provide an allyl boron compound and a zinc-catalyzed cyclopropene preparation method and application to overcome the problems existing in the prior art. The present invention has the advantages of cheap and easy availability of catalyst, convenient reaction operation, high catalytic efficiency, mild reaction conditions, and large-scale production.

[0004] In order to achieve the above object, the present invention adopts the following technical scheme:

[0005] A method for preparing an allyl boron compound by zinc-catalyzed cyclopropene, using a cyclopropene compound shown in formula (2) and a borane complex shown in formula (3) as raw materials, zinc chloride shown in formula (4) as a catalyst, and dichloromethane shown in formula (5) as a reaction solvent, to obtain an allyl boron compound shown in formula (1) after reaction;

[0006]

[0007]

[0008] Among them, R 1 is an alkyl or aryl group, R 2 is an alkyl group, R 3 is silicon or hydrogen, and LB is ammonia, pyridine, organic phosphorus or nitrogen heterocyclic carbene.

[0009] Further, the specific process is as follows:

[0010] Under nitrogen protection, zinc chloride, cyclopropene compounds, borane complexes and dichloromethane are mixed and reacted at 20° C. for 24 hours. After the reaction is completed, the reaction mixture is purified by column chromatography to obtain an allyl boron compound.

[0011] Furthermore, after zinc chloride, cyclopropene compounds, borane complex and dichloromethane are mixed, the concentration of the cyclopropene compounds is 1 mol / L.

[0012] Furthermore, the amount of the borane complex used is 4 times the amount of the cyclopropene compound.

[0013] Furthermore, the amount of zinc chloride used is 10% of the amount of the cyclopropene compound.

[0014] Further, the purification of the reaction product by column chromatography is specifically as follows:

[0015] Silica gel with a specification of 300 meshes was used, the mass ratio of the silica gel to the reaction product was (50-100):1, the eluent was a mixture of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the mixture was 20:1.

[0016] An allyl boron compound is prepared by the above method.

[0017] An allyl boron compound having the structural formula:

[0018]

[0019]

[0020] Compared with the prior art, the present invention has the following beneficial technical effects:

[0021] The transition metal-catalyzed non-diazocarbene precursor insertion strategy via metal carbene boron hydrogen bond is one of the most direct and effective methods for constructing organic boron compounds. The present invention first discovered that simple ZnCl2 can be used as a catalyst to efficiently catalyze cyclopropene to prepare allyl boron compounds. The method of the present invention has the advantages of cheap and easy catalyst, convenient reaction operation, high catalytic efficiency, mild reaction conditions, and large-scale production. The method of the present invention is not only applicable to 3,3-dialkyl-substituted cyclopropene, but also to 1,3,3-trisubstituted cyclopropene substrates, showing excellent catalytic activity, stereoselectivity and universality. The allyl boron compounds obtained by the present invention can be used for functional group transformation to quickly construct a variety of products. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The following drawings illustrate only certain embodiments of the present invention and therefore should not be considered limiting of the scope.

[0023] Figure 1 is the synthetic route diagram of the present invention;

[0024] Figure 2 Schematic diagram of the application of allyl boron compounds in functional group transformation to quickly construct a variety of products. DETAILED DESCRIPTION

[0025] The present invention is described in further detail below:

[0026] A method for preparing an allyl boron compound by zinc-catalyzed cyclopropene, comprising: using a cyclopropene compound (Formula 2) and a borane complex (Formula 3) as raw materials, zinc chloride (Formula 4) as a catalyst, and dichloromethane (Formula 5) as a reaction solvent; under nitrogen protection, zinc chloride, the cyclopropene compound, the borane complex, and dichloromethane are mixed and reacted at 20° C. for 24 hours; after the reaction is completed, the reaction product is purified by column chromatography to obtain an allyl boron compound (Formula 1).

[0027]

[0028] The reaction is as Figure 1 As shown:

[0029]

[0030] The reaction concentration of the cyclopropene compound is 1 mol / L, the amount of the borane complex is 4 times the amount of the cyclopropene compound, and the amount of the zinc chloride is 10% of the amount of the cyclopropene compound; the column chromatography conditions are: using 300 mesh silica gel, the mass ratio of silica gel to the reaction product is (50-100):1, the eluent is a mixed solution of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the mixed solution is 20:1.

[0031] The allyl boron compound prepared by the present invention comprises:

[0032]

[0033]

[0034] The present invention is described in detail below in conjunction with the embodiments and drawings to facilitate a more comprehensive understanding of the present invention by those skilled in the art, but the present invention is not limited to the scope of all embodiments. All other embodiments obtained without creative work are within the scope of protection of the present invention.

[0035] Example 1

[0036] This example is a gram-level preparation of (2-cyclododecylethyl) borane trimethylamine compound (1A), which specifically includes the following steps: under a nitrogen environment, a cyclopropene compound spiro[2.11]tetradec-1-ene (2A, 0.96 g, 5.0 mmol), borane trimethylamine complex (1.54 g, 20.0 mmol), ZnCl2 (68.2 mg, 0.5 mmol), and dichloromethane (50 mL) are added to a reaction bottle, and the mixture is reacted at 20° C. for 24 h; ② the reaction is purified by column chromatography (using 300 mesh silica gel, the mass ratio of silica gel to the purified product is 50:1, and the eluent is petroleum ether and ethyl acetate, the volume ratio is 20:1) to obtain the allyl boron compound shown in formula 1A (1.20 g, 90% separation yield), and the nuclear magnetic resonance data are as follows: 1 H NMR (500MHz, CDCl3): δ5.38(t,J=7.6Hz,1H),2.56(s,9H),2.09(t,J=6.7Hz,2H),2.00(t,J=6.7Hz,2H),1.55-1.15(m,22H). 13 CNMR (125MHz, CDCl3): δ132.3,129.4,52.2,32.5,27.9,25.0,24.9,24.7,24.61,24.59,24.5,24.1,23.3,22.6.

[0037]

[0038] Example 2

[0039] This example is a gram-level preparation of (E)-3-adamantyl-2-butenyl borane trimethylamine compound (1B), which specifically includes the following steps: under a nitrogen environment, add cyclopropene compound 3 adamantyl-3-methyl-cyclopropene (2B, 0.94 g, 5.0 mmol), borane trimethylamine complex (1.54 g, 20.0 mmol), ZnCl2 (68.2 mg, 0.5 mmol), and dichloromethane (50 mL) into a reaction bottle, and react at 20° C. for 24 h; ② the reaction is purified by column chromatography (using 300 mesh silica gel, the mass ratio of silica gel to the reaction product is 100:1, the eluent is petroleum ether and ethyl acetate, the volume ratio is 20:1, and the product is purified to obtain a colorless allyl boron compound of formula 1B (1.20 g, 92% separation yield), and the nuclear magnetic resonance data are as follows: 1 H NMR (500MHz, CDCl3): δ5.35(t,J=7.8Hz,1H),2.56(s,9H),1.96(s,3H),1.73-1.57(m,15H),1.31-1.24(m,2H). 13C NMR (125MHz, CDCl3): δ138.0,125.4,52.3,41.4,37.5,37.4,29.1,11.5.

[0040]

[0041] Example 3

[0042] This embodiment is to prepare 1,1-dimethyl-3-dimethylphenylsilyl-1-allylborane trimethyl compound (1C) at the gram level, which specifically includes the following steps: under a nitrogen environment, 2-dimethylphenylsilyl-3,3-dimethylcyclopropene (1.01 g, 5.0 mmol), borane trimethylamine complex (1.54 g, 20.0 mmol), ZnCl2 (272.8 mg, 2.0 mmol), 1,2-dichloromethane (50 mL) are added to a reaction bottle, and the reaction is carried out at 20° C. for 24 hours; ② the reaction is purified by column chromatography (using 300 mesh silica gel, the mass ratio of silica gel to reaction product is 80:1, and the eluent is petroleum ether and ethyl acetate, the volume ratio is 20:1) to obtain the allyl boron compound shown in formula 1C (0.4 g, 30% separation yield), and the nuclear magnetic resonance data of the product are: 1 H NMR (500MHz, CDCl3): δ7.57-7.48(m,2H),7.32-7.20(m,3H),5.27(d,J=11.8Hz,1H), 2.45(s,9H),1.62(s,3H),1.33(s,3H),1.28-1.23(m,1H),0.23(s,3H),0.17(s,3H). 13 C NMR (125MHz, CDCl3): δ142.3,134.2,132.9,127.8,127.0,121.9,52.3,26.0,17.8,-2.9,-3.0.

[0043]

[0044] Example 4

[0045] This example is a gram-level preparation of a (2-cyclododecylethyl) borane pyridine compound (1D), which specifically includes the following steps: under a nitrogen environment, a cyclopropene compound spiro[2.11]tetradec-1-ene (2A, 0.96 g, 5.0 mmol), a borane pyridine complex (1.86 g, 20.0 mmol), ZnCl2 (68.2 mg, 0.5 mmol), and dichloromethane (50 mL) are added to a reaction bottle, and the mixture is reacted at 20° C. for 24 h; ② the reaction is purified by column chromatography (using 300 mesh silica gel, a silica gel to be purified mass ratio of 50:1, and an eluent of petroleum ether and ethyl acetate, a volume ratio of 20:1) to obtain an allyl boron compound represented by formula 1D (0.94 g, 66% separation yield), and the NMR data are as follows: 1 H NMR (500MHz, CDCl3): δ8.54(d,J=5.2Hz,2H),7.96-7.88(m,1H),7.52-7.42(m,2H),5.35(t,J =8.0Hz,1H),1.92(t,J=7.0Hz,1H),1.63-1.57(m,2H),1.46-1.40(m,4H),1.33-1.13(m,18H). 13 C NMR (125MHz, CDCl3): δ147.1,139.1,132.9,129.6,125.0,32.3,27.1,24.8,24.72,24.68,24.5,24.2,24.0,23.2,22.4.

[0046]

[0047] Example 5

[0048] This example is to prepare a (2-cyclododecylethyl) borane dimethylphenylphosphine compound (1E) at a gram level, specifically comprising the following steps: under a nitrogen environment, a cyclopropene compound spiro[2.11]tetradec-1-ene (2A, 0.96 g, 5.0 mmol), a borane dimethylphenylphosphine complex (3.04 g, 20.0 mmol), ZnCl2 (68.2 mg, 0.5 mmol), and dichloromethane (50 mL) were added to a reaction bottle, and the mixture was reacted at 20° C. for 24 h; ② the reaction was purified by column chromatography (using 300 mesh silica gel, a silica gel to be purified mass ratio of 50:1, and an eluent of petroleum ether and ethyl acetate, a volume ratio of 20:1) to obtain an allyl boron compound (1.10 g, 64% separation yield) as shown in formula 1E, and the NMR data are as follows: 1H NMR (500MHz, CDCl3): δ7.75-7.58(m,2H),7.55-7.36(m,3H),5.35(t,J=7.5Hz,1H),2.04-1.85(m,4H),1.51(d,J=10.0Hz,6H),1.48-1.24(m,22H). 13 C NMR (125MHz, CDCl3): δ131.6,131.5,131.4,131.13,131.06,131.03,131.0,130.7,12 8.95,128.87,32.4,27.8,24.9,24.8,24.7,24.5,24.3,24.0,23.3,22.5,11.5,11.2.

[0049]

[0050] Example 6

[0051] This example is to prepare a (2-cyclododecylethyl) borane carbene compound (1F) at a gram level, specifically comprising the following steps: under a nitrogen environment, add a cyclopropene compound spiro[2.11]tetradec-1-ene (2A, 0.96 g, 5.0 mmol), a borane carbene complex (2.24 g, 20.0 mmol), ZnCl2 (68.2 mg, 0.5 mmol), and dichloromethane (50 mL) into a reaction flask, and react at 20° C. for 24 h; ② the reaction is purified by column chromatography (using 300 mesh silica gel, a silica gel to be purified mass ratio of 5:1, and an eluent of petroleum ether and ethyl acetate, a volume ratio of 20:1) to obtain an allyl boron compound represented by formula 1F (0.15 g, 10% separation yield), and the NMR data are as follows: 1 H NMR (500MHz, CDCl3): δ4.33(d,J=7.8Hz,1H),3.61(d,J=6.4Hz,2H),3.24(s,6H),2 .18(t,J=6.6Hz,2H),2.03(t,J=6.6Hz,2H),1.54-1.46(m,4H),1.43-1.23(m,20H). 13 C NMR (125MHz, CDCl3): δ144.5,112.4,45.6,35.5,31.7,30.7,29.9,25.4,25.1,24.4,24.2,24.1,23.6,23.4,23.3,22.4,9.3.

[0052]

[0053] Example 7

[0054] This example is to prepare a (2-cyclododecylethyl) borane nitrogen methyl pyrrolidine compound (1G) at a gram level, specifically comprising the following steps: under a nitrogen environment, a cyclopropene compound spiro [2.11] tetradec-1-ene (2A, 0.96 g, 5.0 mmol), a borane nitrogen methyl pyrrolidine complex (2.06 g, 20.0 mmol), ZnCl2 (68.2 mg, 0.5 mmol), and dichloromethane (50 mL) were added to a reaction bottle, and the reaction was carried out at 20° C. for 24 h; ② the reaction was purified by column chromatography (using 300 mesh silica gel, the mass ratio of silica gel to the purified product was 5:1, and the eluent was petroleum ether and ethyl acetate, the volume ratio was 20:1) to obtain an allyl boron compound represented by formula 1G (1.23 g, 84% separation yield), and the NMR data are as follows: 1 H NMR (500MHz, CDCl3): δ5.39(t,J=7.8Hz,1H),3.29-3.13(m,2H),2.78-2.68(m,2H),2.55(s,3H),2.14-1.86(m,8H),1.60-1.15(m,22H). 13 C NMR (125MHz, CDCl3): δ132.0,129.7,61.3,48.4,32.5,27.8,24.94,24.90,24.7,24.60,24.57,24.4,24.1,23.3,22.8,22.5.

[0055]

[0056] Example 8

[0057] This example is a gram-level preparation of (2-cyclododecylethyl) borane dimethylamine compound (1G), which specifically includes the following steps: under a nitrogen environment, a cyclopropene compound spiro[2.11]tetradec-1-ene (2A, 0.96 g, 5.0 mmol), borane dimethylamine complex (1.26 g, 20.0 mmol), ZnCl2 (68.2 mg, 0.5 mmol), and dichloromethane (50 mL) are added to a reaction bottle, and the mixture is reacted at 20° C. for 24 h; ② the reaction is purified by column chromatography (using 300 mesh silica gel, the mass ratio of silica gel to the purified product is 5:1, and the eluent is petroleum ether and ethyl acetate, the volume ratio is 20:1) to obtain an allyl boron compound represented by formula 1H (0.9 g, 72% separation yield), and the NMR data are as follows: 1H NMR (500MHz, CDCl3): δ5.35 (t, J = 8.0 Hz, 1H), 3.27 (s, 1H), 2.51 (d, J = 5.9 Hz, 6H), 2.08 (t, J = 6.8 Hz, 2H), 2.01 (t, J = 7.0 Hz, 2H), 1.55-1.12 (m, 22H). 13 C NMR (125MHz, CDCl3): δ134.0,129.5,42.6,32.6,27.7,25.0,24.8,24.7,24.65,24.5,24.4,24.2,23.2,22.5.

[0058]

[0059] Example 9

[0060] This example is a gram-level (E)-3-phenyl-2-butenyl borane trimethylamine compound (1I), which specifically includes the following steps: under a nitrogen environment, add a cyclopropene compound spiro 3,3-methylphenyl cyclopropene (0.65g, 5.0mmol), a borane trimethylamine complex (1.54g, 20.0mmol), ZnCl2 (68.2mg, 0.5mmol), and dichloromethane (50mL) into a reaction bottle, and react at 20°C for 24h; ② the reaction is purified by column chromatography (using 300 mesh silica gel, the mass ratio of silica gel to the purified product is 5:1, and the eluent is petroleum ether and ethyl acetate, the volume ratio is 20:1) to obtain an allyl boron compound represented by formula 1H (0.65g, 64% separation yield), and the nuclear magnetic resonance data are as follows: 1 H NMR (500MHz, CDCl3): δ7.38(d,J=7.6Hz,2H),7.25(t,J=7.6Hz,2H),7.12(t,J= 7.2Hz,1H),6.12(t,J=8.0Hz,1H),2.58(s,9H),2.05(s,3H),1.55-1.45(m,2H). 13 C NMR (125MHz, CDCl3): δ145.2,134.5,128.7,128.0,125.4,125.3,52.3,15.3.

[0061]

[0062]

[0063] The products prepared in Example 1 and Example 2 of the present invention are compared with the reported catalytic system Cu(MeCN)4PF6 and JohnPhos combination, as shown in Table 1.

[0064] Table 1 is compared with the reported catalytic systems

[0065]

[0066] It can be seen from Table 1 that the catalytic system used in the present invention is cheap and readily available, has higher catalytic activity and selectivity, and can efficiently prepare allyl boron compounds.

[0067] The allyl boron compound obtained by the preparation method of the present invention can be used for functional group transformation to quickly construct a variety of products. Figure 2 As shown, taking 1A as an example, it can be efficiently converted into various organic substances such as products 6, 7, 8, 9, 10, etc.

[0068] The specific conversion process is as follows:

[0069] (I) 1A and water were used as the reaction raw materials, air was used as the oxidant, and tetrahydrofuran was used as the reaction solvent. The product 3-cyclododecylallyl-1-ol 6 could be obtained in high yield at 60°C; (II) 1A, benzaldehyde and water were used as the reaction raw materials, and tetrahydrofuran was used as the reaction solvent. The product 2-cyclododecyl-1-phenylprop-2-ene-1-ol 7 could be efficiently obtained at 60°C; (III) 1A and pinacol in tetrahydrofuran solution could obtain 2-(2-cyclododecylethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborane 8 in high yield at 70°C; (IV) 1A and N-methyliminodiacetic acid were used as the raw materials, toluene and dimethyl sulfoxide were used as the solvent, and 9 could be obtained in high yield at 70°C; (V) 1A and N-chlorosuccinimide were used as the raw materials and dichloromethane was used as the solvent. Chloro(2-cyclododecylallyl)boranetrimethylamine 10 could be obtained at room temperature.

Claims

1. A method for preparing allyl boron compounds by zinc-catalyzed cyclopropene, characterized in that: Using a cyclopropene compound represented by formula (2) and a borane complex represented by formula (3) as raw materials, zinc chloride represented by formula (4) as a catalyst, and dichloromethane represented by formula (5) as a reaction solvent, an allyl boron compound represented by formula (1) is obtained after reaction; The specific process is as follows: Under nitrogen protection, zinc chloride, cyclopropene compounds, borane complexes and dichloromethane are mixed and reacted at 20° C. for 24 hours. After the reaction is completed, the reaction mixture is purified by column chromatography to obtain an allyl boron compound; Wherein, after zinc chloride, cyclopropene compounds, borane complexes and dichloromethane are mixed, the concentration of the cyclopropene compounds is 1 mol / L, the amount of the borane complexes is 4 times the amount of the cyclopropene compounds, the amount of the zinc chloride is 10% of the amount of the cyclopropene compounds, and the reaction product is purified by column chromatography as follows: 300-mesh silica gel is used, the mass ratio of the silica gel to the reaction product is (50-100):1, the eluent is a mixture of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate in the mixture is 20:1.

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