Synthesis method of gamma-boryl alkylamine compound

Abstract

The invention provides a synthesis method of a gamma-boryl alkylamine compound, and belongs to the field of organic synthesis and fine chemicals. According to the method, olefin is used as a reaction raw material, bis (pinacol) diboron (B2pin2) is used as a boron source, carbene copper is used as a catalyst, nitrone is used as an electrophilic reagent, beta-boryl alkyl copper generated by olefin is captured, an obtained intermediate is not separated, sodium triacetoxyborohydride is used for reduction, and the gamma-boryl alkylamine compound is successfully prepared through a one-pot two-step method. According to the method, commercially available carbene copper is used as a catalyst, olefin and nitrone which are low in price and easy to obtain are used as raw materials, the reaction condition is mild, the substrate application range is wide, and excellent regioselectivity is achieved. The method disclosed by the invention has important significance in the fields of medicines, materials, fine chemical engineering and the like.

Description

Technical Field

[0001] The invention relates to a method for synthesizing a gamma-boryl alkylamine compound, and belongs to the field of organic synthesis and fine chemicals. Background Art

[0002] The synthesis of γ-borylalkylamines has important scientific significance and application value. Alkylamines are important components of many bioactive molecules and drugs. Boronate groups can be efficiently derivatized through Suzuki coupling, oxidation or deboronation reactions. The precise introduction of boronate groups into the γ position of alkylamines combines the biological activity of amine compounds with the functional adjustability of boron atoms. At present, it has become a key platform for organic synthesis and functional molecule design. On the other hand, copper-catalyzed olefin borylation difunctionalization is a hot topic in synthetic chemistry research. Boron and another functional group can be introduced simultaneously on the carbon-carbon double bond. In addition to generating alkyl borylate structural units that are easy to further derivatize, this difunctionalization reaction can also enhance the complexity and diversity of olefin structures. Copper-catalyzed olefin borylation difunctionalization is to generate β-borylalkyl copper intermediates by the addition of Cu-Bpin species to olefins, and then use electrophilic reagents to capture the intermediates to complete the transformation. When imines are used as electrophilic reagents, γ-borylalkylamine compounds can be precisely constructed.

[0003] However, there is a key challenge in this type of reaction: the Cu-Bpin intermediate can simultaneously add to the C=C bond of the olefin and the C=N bond of the imine, resulting in a competitive reaction. The first breakthrough was achieved by the Lam team, who used N-Boc imine as a capture agent to successfully synthesize γ-borylalkylamines (the boryl group was subsequently oxidized to a hydroxyl group) (Chem. Commun., 2016, 52, 3770). The Kanai team used N-thiophosphoramidite as an electrophilic reagent and also completed the borylation α-aminoalkylation reaction of vinyl aromatics (Angew. Chem., 2018, 130, 8397). However, reactions involving N-aryl imines remain challenging. Recently, the Xiong team (Org. Lett., 2018, 20, 1798) and the Xu team (Org. Lett., 2018, 20, 1777) independently reported intramolecular strategies, using N-aryl imines as electrophilic capture reagents to successfully construct five-membered ring compounds through cyclization reactions. Subsequently, the Hoinillos team (Chem. Sci., 2021, 12, 15291) demonstrated another case of intramolecular reactivity, achieving the cyclization of a seven-membered ring. In view of these important advances, using simple and readily available precursors instead of N-aryl imines to achieve intermolecular copper-catalyzed borylation α-aminoalkylation reactions will have important scientific significance and synthetic value.

[0004] The present invention uses olefin as a reaction raw material, bis(pinacol)diboron (B 2 pin 2 ) as a boron source, copper carbene as a catalyst, nitrone as an electrophilic reagent, and the β-boryl alkyl copper generated from the olefin is captured. The intermediate is not separated and sodium triacetoxyborohydride ((CH 3 COO 3 BHNa) reduction, a one-pot two-step method, successfully prepared γ-boryl alkylamine compounds. The olefin and nitrone raw materials used in the present invention are cheap and easy to obtain, carbene copper is commercially available, the method is simple to operate, the reaction conditions are mild, the substrate applicability is wide, and it has good selectivity. Summary of the invention

[0005] The object of the present invention is to provide a method for synthesizing a γ-borylalkylamine compound: using olefin as a reaction raw material, bis(pinacol)diboron (B 2 pin 2 ) as the boron source, nitrone as the electrophilic reagent, copper carbene as the catalyst, the intermediate obtained is not separated, and sodium triacetoxyborohydride ((CH 3 COO 3 BHNa) reduction, a one-pot two-step method for the synthesis of γ-borylalkylamines.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides a method for synthesizing a γ-borylalkylamine compound, and the synthesis path thereof is as follows:

[0007]

[0008] The present invention provides a method for synthesizing a γ-borylalkylamine compound, the steps of which are as follows:

[0009] A carbene copper catalyst, bis(pinacol)diboron shown in general formula 2, a base and a nitrone shown in general formula 3 are added to a dry Schlenk reaction tube equipped with a stirrer, and a Schlenk double-row tube is used to evacuate and introduce argon gas, which is repeated three times. While introducing argon gas, a solvent is added, and after stirring for 10 minutes, an olefin shown in general formula 1 is added, and the reaction system is sealed, and the temperature of the reaction system is controlled at 25 to 35° C. After stirring for 36 to 48 hours, (CH 3 COO 3 BHNa and toluene are heated to 100°C, stirred for 12 hours, cooled to room temperature, the reaction solution is concentrated, and the concentrate is separated by silica gel column chromatography to obtain γ-boryl fatty amine shown in general formula 4;

[0010] Wherein Ar in Formula 1, Formula 3 and Formula 4 1 ,Ar 2 and Ar 3The carbene copper catalyst is selected from one of IMesCuCl, IPrCuCl, SIMesCuCl and SIPrCuCl; the base is selected from one of sodium tert-butoxide, potassium tert-butoxide and lithium tert-butoxide; the solvent is selected from one of toluene, n-hexane and 1,4-dioxane.

[0011] In the steps of the above method, the molar ratio of olefin 1: bis(pinacol)diboron 2: nitrone 3: base: copper carbene is 1.0: 3.0-4.0: 3.0-4.0: 3.0-4.0: 0.1-0.2. DETAILED DESCRIPTION

[0012] The following examples will help to understand the present invention, but they are not intended to limit the present invention.

[0013] Example 1: Synthesis of N,1,2-triphenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine

[0014]

[0015] To a dry Schlenk reaction tube equipped with a stirrer, 29 mg (0.06 mmol) of carbene cuprous chloride IPrCuCl, 228.6 mg (0.9 mmol) of bis(pinacol)diboron, 86 mg (0.9 mmol) of sodium tert-butoxide and 177 mg (0.9 mmol) of N,1-diphenylmethamine oxide were added. The Schlenk double-row tube was used to evacuate the tube and introduce argon gas. This was repeated three times. While introducing argon gas, 2 mL of toluene was added. After stirring for 10 minutes, 35 uL (0.3 mmol) of styrene was added. The reaction system was sealed and the temperature of the reaction system was controlled at 25 ° C. After stirring for 48 hours, 127 mg (0.6 mmol) of (CH 3 COO 3 BHNa and 1 mL of toluene were heated to 100°C, stirred for 12 hours, cooled to room temperature, and the reaction solution was concentrated. The concentrate was separated by silica gel column chromatography to obtain N,1,2-triphenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine with a yield of 65% and dr=78:22; 1 H NMR (500 MHz, CDCl 3)δ7.28-7.24(m,5H major+2H minor),7.23-7.09(m,4Hmajor+7H minor),7.05-6.95(m,3H major+3H minor),6.60-6.53(m,1H major+1Hminor),6.49(d,J=8.0Hz,2H minor),6.35(d,J=8.0Hz,2H major),4.48(d,J=6.1Hz,1Hminor),4.39(d,J=7.1Hz,1H major),4.11(s,1H major),3.32(dd,J=14.6,7.3Hz,1Hminor),3.19(dd,J=16.2,6.9Hz,1H major),1.38(dd,J=15.7,6.8Hz,1H minor),1.22-1.17(m,1H major+1H minor),1.13-1.08(m,1H major+7H minor),1.05-0.96(m,12Hmajor+6H minor); 13 C NMR(126MHz,CDCl 3 )δ142.97(minor),142.39(major),129.19(minor),129.07(major),128.66(minor),128.56(major),128.53(major),128.10(minor),127.12(major),126.70(minor),126.61(major),126.41(minor),125.16(major),124.97(minor),124.21(major),123.61(minor),118.30(major),118.01(minor),114.20(major),114.10(minor),83.38(minor),83.27(major),61.22(major),60.44(minor),48.88(major),48.16(minor),24.96(minor),24.87(major),24.72(minor),24.59(major); 11 B NMR(160MHz,CDCl 3 )δ34.22;HRMS(ESI)m / z:calculated for[C 27 H 32 BNO 2+H] + 414.2604, found 414.2607.

[0016] Example 2: Synthesis of N,1-diphenyl-2-(4-methylphenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine

[0017]

[0018] To a dry Schlenk reaction tube equipped with a stirrer, 29 mg (0.06 mmol) of carbene cuprous chloride SIPrCuCl, 305 mg (1.2 mmol) of bis(pinacol)diboron, 96 mg (1.2 mmol) of lithium tert-butoxide and 236 mg (1.2 mmol) of N,1-diphenylmethamine oxide were added. The Schlenk double-row tube was used to evacuate the tube and introduce argon gas. This was repeated three times. While introducing argon gas, 2 mL of toluene was added. After stirring for 10 minutes, 40 uL (0.3 mmol) of 4-methylstyrene was added. The reaction system was sealed and the temperature of the reaction system was controlled at 25 ° C. After stirring for 48 hours, 127 mg (0.6 mmol) of (CH 3 COO 3 BHNa and 1 mL of toluene were heated to 100°C, stirred for 12 hours, cooled to room temperature, and the reaction solution was concentrated. The concentrate was separated by silica gel column chromatography to obtain N,1-diphenyl-2-(4-methylphenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine with a yield of 62% and dr=90:10; 1 H NMR (500 MHz, CDCl 3)δ7.31-7.18(m,4H major+4H minor),7.17-6.93(m,7H major+5H minor),6.89(d,J=7.9Hz,2H minor),6.59-6.63(m,1H major+1Hminor),6.48(d,J=7.9Hz,2H minor),6.35(d,J=7.9Hz,2H major),4.47(d,J=6.0Hz,1Hminor),4.38(d,J=7.0Hz,1H major),4.12(s,1H major),3.31(dd,J=14.9,7.0Hz,1Hminor),3.16(dd,J=16.3,6.9Hz,1H major),2.30(s,3H major),2.26(s,3H minor),1.19-1.14(m,1H major+1H minor),1.12-1.08(m,1H major+7H minor),1.05-1.00(m,12Hmajor+6H minor); 13 C NMR(126MHz,CDCl 3 )δ147.89(major),142.85(major),139.42(major),136.36(major),129.08(major),128.96(major),128.66(minor),128.57(minor),128.41(major),128.26(major),127.89(minor),127.84(major),127.00(major),117.14(major),113.81(minor),113.64(major),83.28(minor),83.17(major),64.41(major),64.03(minor),48.18(major),47.06(minor),24.96(minor),24.86(major),24.67(minor),24.61(major),21.18(major); 11 B NMR(160MHz,CDCl 3 )δ33.92,22.51;HRMS(ESI)m / z:calculated for[C 28 H 34 BNO 2 +H] +428.2761, found 428.2766.

[0019] Example 3: Synthesis of N,1-diphenyl-2-(3-chlorophenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine

[0020]

[0021] To a dry Schlenk reaction tube equipped with a stirrer, 24 mg (0.06 mmol) of carbene cuprous chloride IMesCuCl, 305 mg (1.2 mmol) of bis(pinacol)diboron, 135 mg (1.2 mmol) of potassium tert-butoxide and 236 mg (1.2 mmol) of N,1-diphenylmethamine oxide were added. The Schlenk double-row tube was used to evacuate the mixture and argon was introduced. This was repeated three times. While argon was introduced, 2 mL of n-hexane was added. After stirring for 10 minutes, 38 uL (0.3 mmol) of 3-chlorostyrene was added. The reaction system was sealed and the temperature of the reaction system was controlled to 35 ° C. After stirring for 48 hours, 127 mg (0.6 mmol) of (CH 3 COO 3 BHNa and 1 mL of toluene were heated to 100°C, stirred for 12 hours, cooled to room temperature, and the reaction solution was concentrated. The concentrate was separated by silica gel column chromatography to obtain N,1-diphenyl-2-(3-chlorophenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine with a yield of 50% and dr=89:11; 1 H NMR (500 MHz, CDCl 3)δ7.30-7.28(m,3H major+1Hminor),7.27-7.22(m,1H major+4H minor),7.20-7.19(m,3H major),7.17-7.04(m,2Hmajor+6H minor),7.01(t,J=7.9Hz,2H major),6.67-6.60(m,1H major+1H minor),6.58(d,J=7.7Hz,2H minor),6.45(d,J=7.8Hz,2H major),4.49(d,J=7.2Hz,1H minor),4.42(d,J=7.6Hz,1H major),3.38-3.34(m,1H minor),3.33-3.20(m,1H major),1.14(s,6H minor),1.12-1.08(m,2H major+8H minor),1.03(d,J=19.6Hz,12H major); 13 C NMR(126MHz,CDCl 3 )δ146.58(major),144.84(minor),134.11(major),133.66(minor),129.64(major),129.09(minor),129.03(major),128.93(major),128.80(minor),128.30(major),127.97(minor),127.79(major),127.59(minor),127.32(major),127.02(major),126.51(minor),126.47(major),118.14(minor),114.26(major),83.36(minor),83.22(major),64.82(major),48.33(minor),47.98(major),24.86(minor),24.75(major),24.57(minor),24.46(major); 11 B NMR(160MHz,CDCl3)634.21;HRMS(ESI)m / z:calculated for[C 27 H 31 BClNO 2 +H] + 448.2215,found 448.2217。

[0022] Example 4: Synthesis of N,1-diphenyl-2-(2-bromophenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine

[0023]

[0024] To a dry Schlenk reaction tube equipped with a stirrer, 24 mg (0.06 mmol) of carbene cuprous chloride SIMesCuCl, 305 mg (1.2 mmol) of bis(pinacol)diboron, 115 mg (1.2 mmol) of sodium tert-butoxide and 236 mg (1.2 mmol) of N, 1-diphenylmethamine oxide were added. The Schlenk double-row tube was used to evacuate the mixture and argon was introduced. This was repeated three times. While argon was introduced, 2 mL of 1,4-dioxane was added. After stirring for 10 minutes, 38 uL (0.3 mmol) of 2-bromostyrene was added. The reaction system was sealed and the temperature of the reaction system was controlled to 35 ° C. After stirring for 48 hours, 127 mg (0.6 mmol) of (CH 3 COO 3 BHNa and 1 mL of toluene were heated to 100°C, stirred for 12 hours, cooled to room temperature, and the reaction solution was concentrated. The concentrate was separated by silica gel column chromatography to obtain N,1-diphenyl-2-(2-bromophenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine with a yield of 40% and dr=77:23; 1 H NMR (500 MHz, CDCl 3 )δ7.56 (d, J=7.9Hz, 1H major), 7.32-7.14 (m, 7H major+11H minor), 7.06-7.02 (m, 1H major), 6.96 (d, J=7.6Hz, 2H major), 6.56-6.51 (m, 1H major+1H minor), 6.42-6.32 (m, 2H major+2H minor), 4.54(s, 1H major), 4.39-4.30(m, 1H major+1H minor), 3.81(s, 1H major), 3.19(dd, J=16.6, 6.8Hz, 1H minor), 1.24-1.04(m, 2H major+2H minor), 1.02-0.94(m, 12H major+12Hminor); 13 C NMR (126 MHz, CDCl 3)δ147.81(minor), 147.48(major), 143.06(minor), 142.66(minor), 142.62(minor), 141.76(minor), 132.67(major), 129.13(minor), 128.98(maj or), 128.95(major), 128.81(minor), 128.57(major), 128.44(major), 128.33(major), 128.29(minor), 128.15(minor), 128.07(major), 127.84(m ajor), 127.79(major), 127.31(major), 127.09(minor), 126.95(minor), 117.23(minor), 117.02(major), 113.64(minor), 113.46(major), 83.28( major), 83.19(major), 65.10(minor), 64.54(major), 48.60(major), 45.93(minor), 24.84(minor), 24.82(major), 24.58(minor), 24.35(major); 11 B NMR (160 MHz, CDCl 3 )δ33.40, 22.45; HRMS(ESI)m / z: calculatedfor[C 27 H 31 BBr 2 +H] + 492.1709, found 492.1713.

[0025] Example 5: Synthesis of N,1-diphenyl-2-(naphthalen-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine

[0026]

[0027] To a dry Schlenk reaction tube equipped with a stirrer, 12 mg (0.03 mmol) of carbene cuprous chloride IMesCuCl, 228 mg (0.9 mmol) of bis(pinacol)diboron, 86 mg (0.9 mmol) of sodium tert-butoxide and 177 mg (0.9 mmol) of N, 1-diphenylmethamine oxide were added. The Schlenk double-row tube was used to evacuate the mixture and argon was introduced. This was repeated three times. Under the argon introduction, 2 mL of toluene was added. After stirring for 10 minutes, 46 mg (0.3 mmol) of 2-vinylnaphthalene was added. The reaction system was sealed and the temperature of the reaction system was controlled to 30°C. After stirring for 36 hours, 127 mg (0.6 mmol) of (CH 3 COO 3 BHNa and 1 mL of toluene were heated to 100°C, stirred for 12 hours, cooled to room temperature, and the reaction solution was concentrated. The concentrate was separated by silica gel column chromatography to obtain N,1-diphenyl-2-(naphthalene-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine with a yield of 61% and dr=80:20; 1 H NMR (500 MHz, CDCl 3)δ7.94-7.87(m,1H minor),7.81-7.9(m,1Hmajor+1H minor),7.75(d,J=8.4Hz,1H major),7.72-7.70(m,1H major+1H minor),7.65(d,J=8.4Hz,1H minor),7.49-7.40(m,3H major+1H minor),7.35-7.34(m,1H major+3Hminor),7.29(t,J=7.0Hz,3H major),7.247.23(m,3H minor),7.16-7.03(m,2H major+3Hminor),6.97(t,J=7.8Hz,2H major),6.64-6.57(m,1H major+1H minor),6.54(d,J=7.4Hz,2H minor),6.40(d,J=6.3Hz,2H major),4.62(d,J=6.7Hz,1H minor),4.52(d,J=7.6Hz,1H major),3.57(dd,J=14.0,7.0Hz,1H minor),3.46(s,1H major),1.30-1.25(m,1H major+2H minor),1.19(dd,J=15.5,5.9Hz,1H major),1.04(d,J=35.0Hz,12Hminor),0.93(d,J=17.0Hz,12H major); 13 C NMR(126MHz,CDCl 3)δ140.22(major), 134.61(major), 134.13(minor), 133.42(major), 133.31(minor), 132.71(major), 129.90(major), 129.59(minor), 129.33(minor), 129.15 (minor), 129.13 (minor), 128.99 (major), 128.62 (minor), 128.58 (minor), 128.37 (major), 128.25 (minor), 128.00 (minor), 127.94 (major), 127.8 (d, J=3.3Hz major), 127.73 (major), 127.62 (minor), 127.53 (major), 127.23 (d, J=3.8Hz major), 126.50(major), 126.10(major), 125.65(major), 121.04(major), 120.81(minor), 117.51(major), 113.98(minor), 113.87 (major), 83.37(minor), 83.23(major), 48.72(major), 47.61(minor), 24.87(major), 24.73(minor), 24.66(minor), 24.55(major); 11 B NMR (160 MHz, CDCl 3 )δ34.17, 22.54; HRMS(ESI)m / z: calculated for[C 31 H 3 4NO 2 B+H] + 464.2761, found 464.2766.

[0028] Example 6: Synthesis of N,1-diphenyl-2-(pyridin-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine

[0029]

[0030] To a dry Schlenk reaction tube equipped with a stirrer, 12 mg (0.03 mmol) of carbene cuprous chloride IMesCuCl, 228 mg (0.9 mmol) of bis(pinacol)diboron, 86 mg (0.9 mmol) of sodium tert-butoxide and 177 mg (0.9 mmol) of N,1-diphenylmethamine oxide were added. The Schlenk double-row tube was used to evacuate the mixture and argon was introduced. This was repeated three times. While argon was introduced, 2 mL of toluene was added. After stirring for 10 minutes, 32 uL (0.3 mmol) of 2-vinylpyridine was added. The reaction system was sealed and the temperature of the reaction system was controlled to 30 ° C. After stirring for 48 hours, 127 mg (0.6 mmol) of (CH 3 COO 3 BHNa and 1 mL of toluene were heated to 100°C, stirred for 12 hours, cooled to room temperature, and the reaction solution was concentrated. The concentrate was separated by silica gel column chromatography to obtain N,1-diphenyl-2-(pyridin-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine with a yield of 73% and dr=90:10; 1 H NMR (500 MHz, CDCl 3 )δ8.64 (d, J=5.0Hz, 1H major), 8.29 (d, J=5.2Hz, 1H minor), 7.74 (t, J=7.7Hz, 1H minor), 7.50 (t, J=7.3Hz, 1H major), 7.46-7.37 (m, 6H minor), 7.29-7.22 (m, 6H major), 7.08-7.01 (m, 2H major+2H minor), 6.64-6.56 (m, 1H major+1H miror), 6.50-6.47 (m, 2H major+2H minor), 6.41 (d, J=8.3Hz, 1H minor), 6.29 (d, J=7.8Hz, 1H major), 4.76 (s, 1H minor), 4.68 (d, J=4.7Hz, 1H major), 4.32-4.25(m, 1H minor), 3.65-3.60(m, 1H major), 2.22-2.11(m, 1H major+1H minor), 2.09-1.92(m, 1H major+1H minor), 1.27(s, 12H minor), 1.24(s, 12H major); 13 C NMR (126 MHz, CDCl 3)δ162.23(major), 148.65(major), 143.85(major), 142.66(major), 139.52(minor), 138.55(major), 128.93(mi nor), 128.85(major), 128.50(minor), 128.47(major), 127.28(major), 127.12(major), 124.91(major), 122.96( major), 116.65(major), 113.79(minor), 113.62(major), 83.05(major), 81.29(major), 63.57(major), 62.59(mi nor), 50.56(minor), 49.95(major), 25.94(major), 25.62(major), 24.98(minor), 24.68(major), 24.23(minor); 11 B NMR (160 MHz, CDCl 3 )δ34.22.HRMS(ESI)m / z: calculated for[C 26 H 31 BN 2 O 2 +H] + 415.2557, found 415.2561.

[0031] Example 7: Synthesis of N,2-diphenyl-1-(4-trifluoromethylphenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine

[0032]

[0033] To a dry Schlenk reaction tube equipped with a stirrer, 12 mg (0.03 mmol) of carbene cuprous chloride IMesCuCl, 228 mg (0.9 mmol) of bis(pinacol)diboron, 86 mg (0.9 mmol) of sodium tert-butoxide and 238 mg (0.9 mmol) of N-phenyl-1-(4-trifluoromethylphenyl)methamine oxide were added. The Schlenk double-row tube was used to evacuate the mixture and argon was introduced. This was repeated three times. While argon was introduced, 2 mL of toluene was added. After stirring for 10 minutes, 35 uL (0.3 mmol) of styrene was added. The reaction system was sealed and the temperature of the reaction system was controlled to 30 ° C. After stirring for 36 hours, 127 mg (0.6 mmol) of (CH 3 COO 3BHNa and 1 mL of toluene were heated to 100°C, stirred for 12 hours, cooled to room temperature, and the reaction solution was concentrated. The concentrate was separated by silica gel column chromatography to obtain N,2-diphenyl-1-(4-trifluoromethylphenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine with a yield of 72% and dr=95:5; 1 H NMR (500 MHz, CDCl 3 )δ7.53 (d, J=7.9Hz, 2H major), 7.47 (q, J=8.2Hz, 4H minor), 7.39 (d, J=7.9Hz, 2H major), 7.29-7.12 (m, 5H major+7H minor), 6.99 (t, J=7.7Hz, 2H major), 6.64-6.57 (m, 1H major+3H major), 6.32 (d, J=8.0Hz, 2H major), 4.48 (d, J=6.9Hz, 1H major), 4.40 (s, 2H major), 4.15 (s, 1H major), 3.22 (dt, J=9.8, 6.6Hz, 1H major), 1.22-1.17 (m, 1H major+7H minor), 1.13-1.08(m, 1H major+7H minor), 1.04-1.00(m, 12H major); 13 C NMR (126 MHz, CDCl 3 )δ147.34(major), 147.00(major), 141.99(major), 129.53(minor), 129.45(minor), 129.27(minor) , 129.11(major), 128.60(major), 128.52(major), 128.16(major), 127.23(major), 125.31(q, J=3.7 Hz, major), 124.41 (q, J=272.1Hz, major), 117.99 (minor), 117.72 (major), 113.65 (major), 113.03 ( minor), 83.42(minor), 83.36(major), 64.14(major), 48.34(major), 24.87(major), 24.60(major); 11 B NMR (160 MHz, CDCl 3 )δ33.87; 19 F NMR (471 MHz, CDCl3 )δ-62.28; HRMS(ESI)m / z: calculated for[C 28 H 31 BF 3 NO 2 +H] + 482.2478, found 482.2481.

[0034] Example 8: Synthesis of N,2-diphenyl-1-(furan-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine

[0035]

[0036] To a dry Schlenk reaction tube equipped with a stirrer, 12 mg (0.03 mmol) of carbene cuprous chloride IMesCuCl, 228 mg (0.9 mmol) of bis(pinacol)diboron, 86 mg (0.9 mmol) of sodium tert-butoxide and 168 mg (0.9 mmol) of 1-(furan-2-yl)-N-phenylmethamine oxide were added. The Schlenk double-row tube was used to evacuate the mixture and argon was introduced. This was repeated three times. While argon was introduced, 2 mL of toluene was added. After stirring for 10 minutes, 35 uL (0.3 mmol) of styrene was added. The reaction system was sealed and the temperature of the reaction system was controlled to 30 ° C. After stirring for 36 hours, 127 mg (0.6 mmol) of (CH 3 COO 3 BHNa and 1 mL of toluene were heated to 100°C, stirred for 12 hours, cooled to room temperature, and the reaction solution was concentrated. The concentrate was separated by silica gel column chromatography to obtain N,2-diphenyl-1-(furan-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine with a yield of 45% and dr=78:22; 1 H NMR (500 MHz, CDCl 3)δ7.36(s,1H major),7.29-7.09(m,5H major+6H minor),7.26-7.10(m,2H major+2H minor),6.68-6.60(m,1H major+3H minor),6.48(d,J=8.0Hz,2H major),6.25(s,1H major),6.13(s,1H minor),6.03(d,J=2.8Hz,1Hmajor),5.85(d,J=2.9Hz,1H minor),4.66-4.59(m,1H major+1H minor),4.12(d,J=8.7Hz,1H minor),3.89(s,1H major),3.48-3.41(m,1H major+1H minor),1.45(dd,J=15.7,7.8Hz,1H minor),1.33-1.26(m,1H major+1H minor),1.19(dd,J=15.5,6.0Hz,1Hmajor),1.11(d,J=30.0Hz,12H minor),1.03(d,J=22.5Hz,12H major); 13 C NMR(126MHz,CDCl 3 )δ155.47(major),154.25(minor),147.63(major),147.19(minor),142.97(minor),142.36(major),141.42(major),141.18(minor),129.21(minor),129.11(major),128.43(minor),128.38(major),128.34(major),127.99(minor),126.88(major),126.59(minor),117.91(minor),117.70(major),114.11(minor),113.63(major),110.31(major),109.98(minor),107.40(minor),107.35(major),83.29(minor),83.20(major),58.32(major),58.25(minor),46.19(major),45.64(minor),24.96(minor),24.85(major),24.75(minor),24.58(major); 11B NMR (160 MHz, CDCl 3 )δ34.38; HRMS(ESI)m / z: calculated for[C 25 H 30 BNO 3 +H] + 426.2216, found 426.2214.

[0037] Example 9: Synthesis of N,2-diphenyl-1-(thiophene-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine

[0038]

[0039] To a dry Schlenk reaction tube equipped with a stirrer, 12 mg (0.03 mmol) of carbene cuprous chloride IMesCuCl, 228 mg (0.9 mmol) of bis(pinacol)diboron, 86 mg (0.9 mmol) of sodium tert-butoxide and 183 mg (0.9 mmol) of N-phenyl-1-(thiophen-2-yl)methamine oxide were added. The Schlenk double-row tube was used to evacuate the mixture and argon was introduced. This was repeated three times. While argon was introduced, 2 mL of toluene was added. After stirring for 10 minutes, 35 uL (0.3 mmol) of styrene was added. The reaction system was sealed and the temperature of the reaction system was controlled to 30 ° C. After stirring for 36 hours, 127 mg (0.6 mmol) of (CH 3 COO 3 BHNa and 1 mL of toluene were heated to 100°C, stirred for 12 hours, cooled to room temperature, and the reaction solution was concentrated. The concentrate was separated by silica gel column chromatography to obtain N,2-diphenyl-1-(thiophen-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine with a yield of 63% and dr=80:20; 1 H NMR (500 MHz, CDCl 3)δ7.29-7.26(m,1H major+3H minor),7.22-7.19(m,3H major+2H minor),7.17-7.15(m,1H major+1H minor),7.12-7.06(m,1Hmajor),7.04-7.01(m,2H major+1H minor),6.94-6.89(m,2H major),6.77(dd,J=4.9,3.6Hz,1H minor),6.68-6.55(m,1H major+5H minor),6.46(d,J=7.8Hz,2H major),4.71(d,J=7.1Hz,1H major),4.28(d,J=7.2Hz,1H minor),4.12(s,1H major),3.34(dd,J=15.5,7.4Hz,1H minor),3.27(dd,J=15.9,7.5Hz,1H major),1.48(dd,J=15.7,7.2Hz,1Hminor),1.34(dd,J=15.7,8.6Hz,1H minor),1.25-1.17(m,2H major),1.10(d,J=27.6Hz,12H minor),1.03(d,J=18.3Hz,12H major).; 13 C NMR(101MHz,CDCl 3 )δ142.40(major),129.21(minor),129.09(major),128.67(minor),128.58(major),128.54(minor),128.11(minor),127.13(major),126.71(minor),126.62(major),126.43(minor),125.17(major),124.98(major),124.23(major),123.63(major),118.32(major),114.21(major),114.11(major),83.39(minor),83.28(major),61.22(major),60.45(minor),48.88(major),48.17(minor),24.97(minor),24.87(major),24.73(minor),24.59(major); 11 B NMR(160MHz,CDCl 3)δ33.09; HRMS(ESI)m / z: calculated for[C 25 H 30 BNO 2 S+H] + 420.2169, found 420.2169.

[0040] Example 10: Synthesis of 1,2-diphenyl-N-(4-iodophenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine

[0041]

[0042] To a dry Schlenk reaction tube equipped with a stirrer, 12 mg (0.03 mmol) of carbene cuprous chloride IMesCuCl, 228 mg (0.9 mmol) of bis(pinacol)diboron, 86 mg (0.9 mmol) of sodium tert-butoxide and 290 mg (0.9 mmol) of N-(4-iodophenyl)-1-phenylmethanimine oxide were added. The Schlenk double-row tube was used to evacuate the mixture and argon was introduced. This was repeated three times. Under the argon introduction, 2 mL of toluene was added. After stirring for 10 minutes, 35 uL (0.3 mmol) of styrene was added. The reaction system was sealed and the temperature of the reaction system was controlled to 30 ° C. After stirring for 36 hours, 127 mg (0.6 mmol) of (CH 3 COO 3 BHNa and 1 mL of toluene were heated to 100°C, stirred for 12 hours, cooled to room temperature, and the reaction solution was concentrated. The concentrate was separated by silica gel column chromatography to obtain N,1-diphenyl-2-(4-iodophenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine with a yield of 61% and dr=77:23; 1 H NMR (500 MHz, CDCl 3)δ7.29-7.18(m,8H major+8H minor),7.16-7.12(m,3H major+3H minor),6.99-6.97(m,1H major+1H minor),6.28(d,J=8.8Hz,1Hminor),6.13(d,J=8.8Hz,2H major),4.51(d,J=6.8Hz,1H minor),4.43(t,J=6.6Hz,1Hminor),4.37-4.33(m,1H major),4.15(s,1H major),3.30(dd,J=15.3,7.1Hz,1Hminor),3.18(dt,J=9.9,6.7Hz,1H major),1.36(dd,J=15.8,7.1Hz,1H minor),1.25-1.22(m,1H minor),1.18(dd,J=15.5,10.1Hz,1H major),1.12-1.04(m,1H major+12Hminor),1.00(d,J=17.2Hz,12H major); 13 C NMR(126MHz,CDCl 3 )δ147.01(major),142.70(minor),142.32(major),141.82(major),140.81(major),137.68(minor),137.56(major),128.68(minor),128.54(major),128.49(major),128.42(major),128.04(minor),128.01(minor),127.77(major),127.70(major),127.35(major),127.10(minor),127.05(minor),126.64(minor),116.08(major),83.41(minor),83.25(major),64.58(major),64.10(minor),48.42(major),47.37(minor),24.96(minor),24.84(major),24.64(minor),24.58(major); 11 B NMR(160MHz,CDCl 3 )δ34.19;HRMS(ESI)m / z:calculated for[C 2 7H 31BINO 2 +H] + 540.1571, found 540.1577.

[0043] Example 11: Synthesis of 1,2-diphenyl-N-(2-methylphenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine

[0044]

[0045] To a dry Schlenk reaction tube equipped with a stirrer, 12 mg (0.03 mmol) of carbene cuprous chloride IMesCuCl, 228 mg (0.9 mmol) of bis(pinacol)diboron, 86 mg (0.9 mmol) of sodium tert-butoxide and 190 mg (0.9 mmol) of N-(2-methylphenyl)-1-phenylmethamine oxide were added. The Schlenk double-row tube was used to evacuate the mixture and argon was introduced. This was repeated three times. While argon was introduced, 2 mL of toluene was added. After stirring for 10 minutes, 35 uL (0.3 mmol) of styrene was added. The reaction system was sealed and the temperature of the reaction system was controlled to 30 ° C. After stirring for 36 hours, 127 mg (0.6 mmol) of (CH 3 COO 3 BHNa and 1 mL of toluene were heated to 100°C, stirred for 12 hours, cooled to room temperature, and the reaction solution was concentrated. The concentrate was separated by silica gel column chromatography to obtain 1,2-diphenyl-N-(2-methylphenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propan-1-amine with a yield of 54% and dr=85:15; 1 H NMR (500 MHz, CDCl 3)δ7.34(d,J=7.3Hz,2H major),7.31-7.13(m,8H major+6H minor),7.08(d,J=7.8Hz,4H minor),6.97(d,J=7.2Hz,1Hminor),6.89(d,J=7.2Hz,1H major),6.90-6.81(m,1H major+1H minor),6.54-6.47(m,1H major+1H minor),6.30(d,J=8.0Hz,1H minor),6.25(d,J=8.0Hz,1H major),4.56(t,J=4.8Hz,1H minor),4.35(d,J=7.7Hz,1H major),4.16(s,1H minor),3.94(s,1Hmajor),3.47-3.40(m,1H minor),3.223.17(m,1H major),2.13(s,3H minor),1.85(s,3Hmajor),1.37-1.27(m,1H major+2H minor),1.12(dd,J=15.4,5.7Hz,1H major),1.05(s,6H major),1.00-0.94(m,12H major+6H minor); 13 C NMR(126MHz,CDCl 3)δ145.47(minor),145.21(minor),142.97(minor),142.62(major),142.57(major),141.33(minor),129.93(minor),129.81(major),128.82(minor),128.60(major),128.57(major),128.41(major),128.07(minor),128.02(minor),127.81(major),127.79(minor),127.17(major),127.11(major),126.97(minor),126.90(minor),126.87(major),126.76(minor),122.48(major),116.99(major),116.77(major),111.47(major),83.26(minor),83.15(major),64.96(major),63.53(minor),49.03(major),47.48(minor),24.87(minor),24.80(major),24.54(major),24.46(minor),17.77(minor),17.33(major); 11 BNMR(160MHz,CDCl 3 )δ34.39;HRMS(ESI)m / z:calculated for[C 28 H 34 BNO 2 +H] + 428.2761,found 428.2763。

Claims

1. A method for synthesizing a γ-borylalkylamine compound, comprising the following steps: A carbene copper catalyst, bis(pinacol)diboron shown in general formula 2, a base and a nitrone shown in general formula 3 are added to a dry Schlenk reaction tube equipped with a stirrer, and a Schlenk double-row tube is used to evacuate, and argon gas is introduced, which is repeated three times. While introducing argon gas, a solvent is added, and after stirring for 10 minutes, an olefin shown in general formula 1 is added, and the reaction system is sealed. The temperature of the reaction system is controlled at 25 to 35° C., and after stirring for 36 to 48 hours, (CH3COO)3BHNa and toluene are added, and the reaction is heated to 100° C., stirred for 12 hours, cooled to room temperature, and the reaction solution is concentrated. The concentrated solution is separated by silica gel column chromatography to obtain a γ-boryl fatty amine shown in general formula 4; Wherein Ar in Formula 1, Formula 3 and Formula 4 1 ,Ar 2 and Ar 3 The carbene copper catalyst is selected from one of IMesCuCl, IPrCuCl, SIMesCuCl and SIPrCuCl; the base is selected from one of sodium tert-butoxide, potassium tert-butoxide and lithium tert-butoxide; the solvent is selected from one of toluene, n-hexane and 1,4-dioxane.

2. The method for synthesizing a γ-borylalkylamine compound according to claim 1, characterized in that The molar ratio of olefin 1: bis(pinacol)diboron 2: nitrone 3: base: copper carbene is 1.0: 3.0-4.0: 3.0-4.0: 3.0-4.0: 0.1-0.2.

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