Method for synthesizing alkyl borate compound by taking allyl alcohol as substrate

Abstract

The invention belongs to the technical field of organic synthesis, and discloses a method for synthesizing an alkyl borate compound by taking allyl alcohol as a substrate, which comprises the following steps: by taking allyl alcohol as shown in a formula I and bis (pinacolato) diboron as substrates and cuprous salt as a catalyst, carrying out a reaction on the allyl alcohol and bis (pinacolato) diboron under the action of alkali, a proton source and a ligand to obtain the alkyl borate compound. And reacting in an organic solvent according to the following reaction formula to obtain the alkyl borate compound as shown in the formula II. The cuprous is adopted to catalyze the bis (pinacolato) diboron to be coupled with the allyl alcohol to synthesize the alkyl borate, so that the substrate range is widened, the use of noble metals and strong reducing agents is avoided, redundant metal wastes are not generated, the green chemistry concept is met, meanwhile, the reaction steps are remarkably shortened, and the cost can be reduced.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis and relates to a method for synthesizing alkyl borate compounds by taking allyl alcohol as a substrate. Background Art

[0002] Organoboron compounds are widely used in many fields such as organic synthesis, catalysis, drug discovery and materials science. In recent years, material chemists have found that organoboron compounds can also be used as very ideal components or precursors for conjugated materials, covalent organic frameworks and hydrogels. In addition, they can also be used as an important class of synthons. In addition to being widely used in transition metal-catalyzed cross-coupling reactions, they can also undergo other functional group transformations to introduce different types of chemical groups. Currently, alkyl borate esters can be synthesized by the following methods:

[0003] (1) Substitution reaction between Grignard reagent and electrophilic boron reagent: The classical synthesis method of aromatic boronic acid (ester) is through the reaction of Grignard reagent or lithium reagent with boric acid ester. Although this method has a high yield, it is not applicable to aromatic halides with functional groups such as ester, cyano, nitro, carbonyl, etc. in the molecule, which limits the scope of substrates (reference: Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457).

[0004] (2) Metal-catalyzed borylation of halogenated hydrocarbons: Ishiyama and Miyaura first reported the borylation reaction of organic halides in 2000 and have made great progress. However, such reactions require the use of halogenated hydrocarbons, and some require the use of precious metal catalysts, which cause environmental pollution and waste of resources, and are not conducive to industrial production (reference: Koji, K.; Hiroaki, I. and Hajime I. Org. Biomol. Chem. 2017, 15, 285–300).

[0005] (3) Transition metal-catalyzed olefin hydroboration: Following the 1985 After the first transition metal Rh-catalyzed hydroboration of catechol borane (i.e., o-phenylenedioxyborane) with olefins, great achievements have been made in the hydroboration of olefins, and transition metals such as copper, nickel, iron, and cobalt as well as non-transition metal catalysis have been achieved for the construction of alkyl boron. However, it still has defects and great difficulties in the preparation of certain olefin raw materials, which increases the cost of such reactions and reduces atom economy (reference: Mannig, D.; Noth, H. Catalytic Hydroboration with Rhodium Complexes. Angew. Chem., Int. Ed. Eng. 1985, 24, 878).

[0006] (4) Transition metal-catalyzed difunctionalization of olefins: After the Marder group achieved the first rhodium-catalyzed diboration of internal olefins in 1998, Miura, Nakao, Brown and others made outstanding contributions to the study of borylation 1,2-difunctionalization reactions. In particular, Professor Keary Engle's group recently achieved regioselective carboboration and amine borylation of non-conjugated olefins under the action of Pd catalysts, realizing the Pd(II)-catalyzed boronic acid difunctionalization of olefins for the first time. However, its disadvantage is that it uses precious metal palladium as a catalyst and has certain limitations in the scope of substrate use (reference: Zhen, L.; Hui-Qi, N.; Tian, ​​Z.; Keary M., E. Catalytic Carbo- and Aminoboration of AlkenylCarbonyl Compounds via Five- and Six-Membered Palladacycles. J. Am. Chem. Soc. 2018, 140, 3223–3227).

[0007] (5) Transition metal-catalyzed borylation of C—H bonds: In 2013, Hartwig’s group reported iridium-catalyzed borylation of benzylic C—H bonds. In addition, C—H bonds at heteroatoms, α-CH bonds, allylic CH bonds, and non-activated C(sp 3 The borylation of )-H bonds has been studied in depth. However, the common disadvantage is that it relies on the use of directing groups to ensure the interaction between the noble metal catalyst and the reactant to achieve the borylation of the CH bond, resulting in a limited range of substrate applications (reference: Seung, HC and John, FIridium-Catalyzed Borylation of Secondary Benzylic C–H Bonds Directed by a Hydrosilane. J. Am. Chem. Soc. 2013, 135, 8157–8160).

[0008] In summary, alkyl borate compounds have important application value in various fields, but the current methods have certain limitations in the synthesis of alkyl borate compounds, not only the substrate application range is limited, or the atom economy is low. Therefore, it is of great significance to develop a new preparation method for alkyl borate compounds. Summary of the invention

[0009] In view of the above technical problems, the present invention provides a method for synthesizing alkyl borate compounds using allyl alcohol as a substrate, wherein monovalent copper is used to catalyze the coupling of pinacol diborate and allyl alcohol to synthesize alkyl borate, thereby broadening the substrate range, avoiding the use of precious metals and strong reducing agents, and not generating excess metal waste, which complies with the concept of green chemistry, and at the same time significantly shortens the reaction steps and can reduce costs.

[0010] To achieve the above object, the present invention adopts the following technical solutions:

[0011] The present invention provides a method for synthesizing an alkyl borate ester compound using allyl alcohol as a substrate, comprising the following steps: using allyl alcohol and biboric acid pinacol ester as substrates and a monovalent copper salt as a catalyst, reacting in an organic solvent according to the following reaction formula in the presence of a base, a proton source and a ligand to obtain an alkyl borate ester compound as shown in formula II;

[0012]

[0013] Wherein: R1 is selected from hydrogen, C1-C3 alkyl, C3-C6 cycloalkyl, phenyl; R2 is selected from phenyl arbitrarily substituted at the para, ortho or meta position, condensed ring aromatic group, five-membered heterocyclic group, cyclohexyl group, substituted cyclohexyl group or cyclohexenyl group, and the substituent on the phenyl group is selected from halogen, trifluoromethyl, C1-C3 alkoxy group, phenyl group.

[0014] The monovalent copper salt in the above technical solution is selected from cuprous chloride, cuprous iodide or cuprous bromide.

[0015] The base in the above technical solution is selected from one of trimethylsiloxy sodium, potassium tert-butoxide or sodium ethoxide.

[0016] The proton source in the above technical solution is selected from one of tert-butyl alcohol, methanol and ethanol.

[0017] The ligand described in the above technical solution is 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene.

[0018] The organic solvent in the above technical solution is selected from one of 1,4-dioxane, tetrahydrofuran or methyl tert-butyl ether.

[0019] The molar amount of the monovalent copper salt in the above technical solution is 5-20% of the molar amount of the allyl alcohol shown in formula I.

[0020] The molar amount of the ligand in the above technical solution is 10-15% of the molar amount of the allyl alcohol shown in formula I.

[0021] The molar amount of the proton source in the above technical solution is 2 to 3 times the molar amount of the allyl alcohol shown in formula I.

[0022] The molar ratio of the allyl alcohol represented by formula I to the bipyraclostrobin in the above technical solution is 1:2-4.

[0023] The molar amount of the base in the above technical solution is 2 to 4 times the molar amount of the allyl alcohol shown in formula I.

[0024] The amount of the organic solvent used in the above technical solution is 10 mL to 30 mL of organic solvent per millimole of the allyl alcohol represented by formula I.

[0025] In the above technical solution, the reaction temperature is 70°C and the reaction time is 24h.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] 1. The method of the present invention uses monovalent copper to catalyze the coupling of pinacol diboric acid ester and allyl alcohol to synthesize alkyl borate ester, which broadens the substrate range, avoids the use of precious metals and strong reducing agents, does not generate excess metal waste, conforms to the concept of green chemistry, and significantly shortens the reaction steps, thereby reducing costs.

[0028] 2. The method of the present invention uses allyl alcohol as a raw material to synthesize alkyl borate, and the yield is high under the action of the ligand 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene. The alkyl borate is unstable and can be oxidized to alcohol in one step, which also broadens the synthesis of alcohol compounds.

[0029] 3. The raw materials in the method of the present invention are cheap and easily available, the operation is simple and safe, the conditions are mild, the reaction yield is high, and it is easy to realize industrial production. DETAILED DESCRIPTION

[0030] The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention. Unless otherwise specified, the technical means used in the examples are conventional means known to those skilled in the art. The test methods in the following examples are conventional methods unless otherwise specified.

[0031] In the following examples and reaction equations, 1 represents allyl alcohol, 2a represents diboronic acid pinacol ester, L13 represents 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, and L1 represents (9,9-dimethyl-9H-xanthen-4,5-diyl)bis(dicyclohexylphosphine).

[0032] Example 1 Synthesis of 3-(4-chlorophenyl)propan-1-ol

[0033] In a glove box filled with argon, 121.9 mg 2a (0.48 mmol, 2.4 equiv), 53.8 mg sodium trimethylsiloxy (0.48 mmol, 2.4 equiv), 12.7 mg ligand L13 (0.022 mmol, 11 mol%), and 4 mg catalyst cuprous iodide (0.02 mmol, 10 mol%) were weighed and placed in a 25 mL Schlenk reaction tube, and then 2.0 mL 1,4-dioxane, 1a (0.2 mmol, 1.0 equiv) and 28 μL tert-butyl alcohol (0.3 mmol, 1.5 equiv) were added. The stopcock was tightened and the reaction was placed in a heater preheated to 70°C for 24 h.

[0034] After the reaction, add an appropriate amount of ethyl acetate to dilute the reaction solution, filter, remove the filter residue, collect the organic phase and spin dry, transfer the product to a round-bottom flask, add 2.0mL tetrahydrofuran, 1.0mL 30% H2O2 (aq) and 1.0mL 1mol / LNaOH (aq) and stir for 5h. After TLC detection, extract with ethyl acetate three times, dry with anhydrous sodium sulfate, and filter. After the organic phase is spin dried, the residue is purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain 21.1mg of colorless oily liquid product 3a with a yield of 62%.

[0035] The above reaction equation is as follows:

[0036]

[0037] 1 H NMR (400MHz, CDCl3) δ7.27–7.23(m,2H),7.16–7.10(m,2H),3.70–3.63(m,2H),2.82–2.75(m,2H),1.90–1.83(m,2H),1.31(br,s,1H); 13 C NMR (101MHz, CDCl3) δ140.3,131.6,129.8,128.5,62.0,34.1,31.4.

[0038] Example 2 Synthesis of 3-(4-(trifluoromethyl)phenyl)propan-1-ol

[0039] In a glove box filled with argon, 121.9 mg 2a (0.48 mmol, 2.4 equiv), 53.8 mg sodium trimethylsiloxy (0.48 mmol, 2.4 equiv), 12.7 mg ligand L13 (0.022 mmol, 11 mol%), and 4 mg catalyst cuprous iodide (0.02 mmol, 10 mol%) were weighed and placed in a 25 mL Schlenk reaction tube, and then 2.0 mL tetrahydrofuran, 1b (0.2 mmol, 1.0 equiv) and 12 μL methanol (0.3 mmol, 1.5 equiv) were added. The stopcock was tightened and the mixture was placed in a heater preheated to 70° C. for 24 h.

[0040] After the reaction, add an appropriate amount of ethyl acetate to dilute the reaction solution, filter, remove the filter residue, collect the organic phase and spin dry, transfer the product to a round-bottom flask, add 2.0mL tetrahydrofuran, 1.0mL 30% H2O2 (aq) and 1.0mL 1mol / LNaOH (aq) and stir for 5h. After TLC detection, extract with ethyl acetate three times, dry with anhydrous sodium sulfate, and filter. After the organic phase is spin dried, the residue is purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain 26.1mg of colorless oily liquid 3b with a yield of 64%.

[0041] The above reaction equation is as follows:

[0042]

[0043] 1 H NMR (400MHz, CDCl3) δ7.54(d,J=6.4Hz,2H),7.31(d,J=6.4Hz,2H),3.71–3.65(m,2H),2.81–2.74(m,2H),1.93–1.87(m,2H),1.50(br,s,1H); 13 C NMR (126MHz, CDCl3) δ146.0,128.7,128.5(q, 2 J C-F =32.8Hz),125.3(q, 3 J C-F =3.7Hz),124.3(q, 1 J C-F =272.2Hz),61.9,33.8,31.9; 19 F NMR (376MHz, CDCl3) δ-62.32.

[0044] Example 3 Synthesis of 3-(4-methoxyphenyl)propan-1-ol

[0045] In a glove box filled with argon, 121.9 mg 2a (0.48 mmol, 2.4 equiv), 53.8 mg sodium trimethylsiloxy (0.48 mmol, 2.4 equiv), 12.7 mg ligand L13 (0.022 mmol, 11 mol%), and 3 mg catalyst cuprous bromide (0.02 mmol, 10 mol%) were weighed and placed in a 25 mL Schlenk reaction tube, and then 2.0 mL methyl tert-butyl ether, 1c (0.2 mmol, 1.0 equiv) and 28 μL tert-butyl alcohol (0.3 mmol, 1.5 equiv) were added. The stopcock was tightened and the mixture was placed in a heater preheated to 70° C. for 24 h.

[0046] After the reaction, add an appropriate amount of ethyl acetate to dilute the reaction solution, filter, remove the filter residue, collect the organic phase and spin dry, transfer the product to a round-bottom flask, add 2.0mL tetrahydrofuran, 1.0mL 30% H2O2 (aq) and 1.0mL 1mol / LNaOH (aq) and stir for 5h. After TLC detection, extract with ethyl acetate three times, dry with anhydrous sodium sulfate, and filter. After the organic phase is spin dried, the residue is purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain 21.6mg of colorless oily liquid 3c with a yield of 65%.

[0047] The above reaction equation is as follows:

[0048]

[0049] 1 H NMR (400MHz, CDCl3) δ7.15–7.08(m,2H),6.86–6.80(m,2H),3.79(s,3H),3.68–3.62(m,2H),2.68–2.60(m,2H),1.89–1.82(m,2H),1.75(br,s,1H); 13 C NMR (101MHz, CDCl3) δ157.8,133.8,129.3,113.8,62.2,55.2,34.4,31.1.

[0050] Example 4 Synthesis of 3-([1,1'-biphenyl]-3-yl)propan-1-ol

[0051] In a glove box filled with argon, 121.9 mg 2a (0.48 mmol, 2.4 equiv), 53.8 mg potassium tert-butoxide (0.48 mmol, 2.4 equiv), 12.7 mg ligand L13 (0.022 mmol, 11 mol%), and 4 mg catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed into a 25 mL Schlenk reaction tube, and then 2.0 mL tetrahydrofuran, 1d (0.2 mmol, 1.0 equiv) and 12 μL methanol (0.3 mmol, 1.5 equiv) were added. The stopcock was tightened and the mixture was placed in a heater preheated to 70°C for 24 h.

[0052] After the reaction, add an appropriate amount of ethyl acetate to dilute the reaction solution, filter, remove the filter residue, collect the organic phase and spin dry, transfer the product to a round-bottom flask, add 2.0mL tetrahydrofuran, 1.0mL 30% H2O2 (aq) and 1.0mL 1mol / LNaOH (aq) and stir for 5h. After the reaction is completed by TLC detection, extract with ethyl acetate three times, dry with anhydrous sodium sulfate, and filter. After the organic phase is spin dried, the residue is purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain 24.2mg of colorless oily liquid 3d with a yield of 53%.

[0053] The above reaction equation is as follows:

[0054]

[0055] 1 H NMR (400MHz, CDCl3) δ7.37–7.31(m,2H),7.27–7.20(m,1H),7.12–7.08(m,1H),7.03–6.98(m,2H),6.97–6.93(m,1H ),6.89–6.86(m,1H),6.86–6.80(m,1H),3.71–3.61(m,2H),2.74–2.64(m,2H),1.91–1.84(m,2H),1.43(br,s,1H); 13 C NMR (101MHz, CDCl3) δ157.27,157.25,143.9,129.7,129.6,123.4,123.1,118.9,118.8,116.3,62.1,34.0,31.9.

[0056] Example 5 Synthesis of 3-(4-chloro-3-methoxyphenyl)propan-1-ol

[0057] In a glove box filled with argon, 121.9 mg 2a (0.48 mmol, 2.4 equiv), 53.8 mg sodium trimethylsiloxy (0.48 mmol, 2.4 equiv), 12.7 mg ligand L13 (0.022 mmol, 11 mol%), and 2 mg catalyst cuprous chloride (0.02 mmol, 10% mol%) were weighed into a 25 mL Schlenk reaction tube, and then 2.0 mL tetrahydrofuran, 1e (0.2 mmol, 1.0 equiv) and 12 μL methanol (0.3 mmol, 1.5 equiv) were added. The stopcock was tightened and the mixture was placed in a heater preheated to 70°C for 24 h.

[0058] After the reaction, add an appropriate amount of ethyl acetate to dilute the reaction solution, filter, remove the filter residue, collect the organic phase and spin dry, transfer the product to a round-bottom flask, add 2.0mL tetrahydrofuran, 1.0mL 30% H2O2 (aq) and 1.0mL 1mol / LNaOH (aq) and stir for 5h. After TLC detection, extract with ethyl acetate three times, dry with anhydrous sodium sulfate, and filter. After the organic phase is spin dried, the residue is purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain 24.0mg of colorless oily liquid 3e with a yield of 60%.

[0059] The above reaction equation is as follows:

[0060]

[0061] 1 H NMR (400MHz, CDCl3) δ7.20 (d, J=2.2Hz, 1H), 7.04 (dd, J=8.4, 2.1Hz, 1H); 6.84 (d, J=8.3Hz, 1H),3.87(s,3H),3.68–3.62(m,2H),2.67–2.59(m,2H),1.88–1.81(m,2H);1.65(br,s,1H); 13 C NMR(101MHz, CDCl3)δ153.2,135.0,130.1,127.5,122.2,112.1,62.0,56.2,34.1,30.9; HRMS(ESI-TOF)m / z Calcd for C 10 H 13 O2NaCl[M+Na] + :223.0502,found:223.0497.

[0062] Example 6 Synthesis of 3-(2-bromo-4,5-dimethoxyphenyl)propan-1-ol

[0063] In a glove box filled with argon, 121.9 mg 2a (0.48 mmol, 2.4 equiv), 53.8 mg sodium trimethylsiloxy (0.48 mmol, 2.4 equiv), 12.7 mg ligand L13 (0.022 mmol, 11 mol%), and 4 mg catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed into a 25 mL Schlenk reaction tube, and then 2.0 mL 1,4-dioxane, 1f (0.2 mmol, 1.0 equiv) and 17 μL ethanol (0.3 mmol, 1.5 equiv) were added. The stopcock was tightened and the reaction was placed in a heater preheated to 70°C for 24 h.

[0064] After the reaction, add an appropriate amount of ethyl acetate to dilute the reaction solution, filter, remove the filter residue, collect the organic phase and spin dry, transfer the product to a round-bottom flask, add 2.0mL tetrahydrofuran, 1.0mL 30% H2O2 (aq) and 1.0mL 1mol / LNaOH (aq) and stir for 5h. After the reaction is completed by TLC detection, extract with ethyl acetate three times, dry with anhydrous sodium sulfate, and filter. After the organic phase is spin dried, the residue is purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain 32.9mg of colorless oily liquid 3f with a yield of 60%.

[0065] The above reaction equation is as follows:

[0066]

[0067] 1 H NMR (400MHz, CDCl3) δ6.98(s,1H),6.73(s,1H),3.84(s,6H),3.71–3.63(m,2H),2.80–2.71(m,2H),1.90–1.82(m,2H),1.72(br,s,1H); 13 C NMR (101MHz, CDCl3) δ148.3,147.8,133.0,115.5,113.9,112.9,62.0,56.1,56.0,33.0,32.0.

[0068] Example 7 Synthesis of 3-(naphthalene-2-yl)propan-1-ol

[0069] In a glove box filled with argon, 121.9 mg 2a (0.48 mmol, 2.4 equiv), 53.8 mg sodium trimethylsiloxy (0.48 mmol, 2.4 equiv), 12.7 mg ligand L13 (0.022 mmol, 11 mol%), and 4 mg catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed into a 25 mL Schlenk reaction tube, and then 2.0 mL tetrahydrofuran was added, followed by 1 g (0.2 mmol, 1.0 equiv) and 17 μL ethanol (0.3 mmol, 1.5 equiv). The stopcock was tightened and the mixture was placed in a heater preheated to 70°C for 24 h.

[0070] After the reaction is completed, add an appropriate amount of ethyl acetate to dilute the reaction solution, filter, remove the filter residue, collect the organic phase and spin dry, transfer the product to a round-bottom flask, add 2.0mL tetrahydrofuran, 1.0mL 30% H2O2 (aq) and 1.0mL 1mol / LNaOH (aq) and stir for 5h. After TLC detection, extract with ethyl acetate three times, dry with anhydrous sodium sulfate, and filter. After the organic phase is spin-dried, the residue is purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain 3g 31.0mg of a colorless oily liquid with a yield of 85%.

[0071] The above reaction equation is as follows:

[0072]

[0073] 1 H NMR (400MHz, CDCl3) δ7.82–7.77(m,3H),7.65(s,1H),7.48–7.41(m,2H),7.38–7.3 3(m,1H),3.74–3.68(m,2H),2.91–2.85(m,2H),2.03–1.96(m,2H),1.96(br,s,1H); 13 CNMR(101MHz, CDCl3)δ139.3,133.6,132.0,127.9,127.6,127.4,127.2,126.4,125.9,125.2,62.2,34.0,32.2.

[0074] Example 8 Synthesis of 3-(1,4(1,4)-diphenylcyclohexane-12-yl)propan-1-ol

[0075] In a glove box filled with argon, 121.9 mg 2a (0.48 mmol, 2.4 equiv), 53.8 mg sodium trimethylsiloxy (0.48 mmol, 2.4 equiv), 12.7 mg ligand L13 (0.022 mmol, 11 mol%), and 4 mg catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed into a 25 mL Schlenk reaction tube, and then 2.0 mL tetrahydrofuran, 1h (0.2 mmol, 1.0 equiv) and 12 μL methanol (0.3 mmol, 1.5 equiv) were added. The stopcock was tightened and the mixture was placed in a heater preheated to 70°C for 24 h.

[0076] After the reaction, add an appropriate amount of ethyl acetate to dilute the reaction solution, filter, remove the filter residue, collect the organic phase and spin dry, transfer the product to a round-bottom flask, add 2.0mL tetrahydrofuran, 1.0mL 30% H2O2 (aq) and 1.0mL 1mol / LNaOH (aq) and stir for 5h. After the reaction is completed by TLC detection, extract with ethyl acetate three times, dry with anhydrous sodium sulfate, and filter. After the organic phase is spin-dried, the residue is purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain 3h 29.8mg of colorless oily liquid, with a yield of 56%.

[0077] The above reaction equation is as follows:

[0078]

[0079] 1 H NMR (400MHz, CDCl3) δ6.69 (dd, J=7.8, 1.9Hz, 1H), 6.52 (dd, J=7.8, 1.9Hz, 1H), 6.47 (dd, J=7. 8,1.9Hz,1H),6.44–6.42(m,2H),6.40(dd,J=7.9,1.9Hz,1H),6.15(s,1H),3.64–3.57(m,2H), 3.40–3.33(m,1H),3.16–3.07(m,2H),3.06–3.03(m,2H),3.03–3.01(m,1H),3.00–2.93(m,1H) ,2.84–2.76(m,1H),2.73–2.66(m,1H),2.41–2.33(m,1H),1.76–1.69(m,2H),1.56(br,s,1H); 13C NMR (101MHz, CDCl3) δ141.1,139.8,139.4,137.5,134.8,134.6,133.3,133.1,1 32.1,130.4,128.8,62.5,35.3,35.0,34.3,33.5,33.3,30.5; HRMS(ESI-TOF)m / z Calcd for C 19 H 22 ONa[M+Na] + :289.1568,found:289.1560.

[0080] Example 9 Synthesis of 3-(Furan-2-yl)propan-1-ol

[0081] In a glove box filled with argon, 121.9 mg 2a (0.48 mmol, 2.4 equiv), 32.7 mg sodium ethoxide (0.48 mmol, 2.4 equiv), 12.7 mg ligand L13 (0.022 mmol, 11 mol%), and 4 mg catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed into a 25 mL Schlenk reaction tube, and then 2.0 mL tetrahydrofuran, 1i (0.2 mmol, 1.0 equiv) and 28 μL tert-butanol (0.3 mmol, 1.5 equiv) were added. The stopcock was tightened and the mixture was placed in a heater preheated to 70°C for 24 h.

[0082] After the reaction, add an appropriate amount of ethyl acetate to dilute the reaction solution, filter, remove the filter residue, collect the organic phase and spin dry, transfer the product to a round-bottom flask, add 2.0mL tetrahydrofuran, 1.0mL 30% H2O2 (aq) and 1.0mL 1mol / LNaOH (aq) and stir for 5h. After TLC detection, extract with ethyl acetate three times, dry with anhydrous sodium sulfate, and filter. After the organic phase is spin-dried, the residue is purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain 15.4mg of colorless oily liquid 3i with a yield of 61%.

[0083] The above reaction equation is as follows:

[0084]

[0085] 1H NMR (400MHz, CDCl3) δ7.33–7.28(m,1H),6.31–6.25(m,1H),6.01(dd,J=3.1,0.9H z,1H),3.75–3.62(m,2H),2.83–2.70(m,2H),1.99–1.83(m,2H),1.34(br,s,1H); 13 CNMR (101MHz, CDCl3) δ155.5,140.8,110.1,104.9,61.7,30.8,24.1.

[0086] Example 10 Synthesis of 3-(cyclohex-1-en-1-yl)propan-1-ol

[0087] In a glove box filled with argon, 121.9 mg 2a (0.48 mmol, 2.4 equiv), 53.8 mg sodium trimethylsiloxy (0.48 mmol, 2.4 equiv), 12.7 mg ligand L13 (0.022 mmol, 11 mol%), and 4 mg catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed into a 25 mL Schlenk reaction tube, and then 2.0 mL 1,4-dioxane, 1j (0.2 mmol, 1.0 equiv) and 56 μL tert-butyl alcohol (0.6 mmol, 3.0 equiv) were added. The stopcock was tightened and the reaction was placed in a heater preheated to 130°C for 36 h.

[0088] After the reaction, add an appropriate amount of ethyl acetate to dilute the reaction solution, filter, remove the filter residue, collect the organic phase and spin dry, transfer the product to a round-bottom flask, add 2.0mL tetrahydrofuran, 1.0mL 30% H2O2 (aq) and 1.0mL 1mol / LNaOH (aq) and stir for 5h. After the reaction is completed by TLC detection, extract with ethyl acetate three times, dry with anhydrous sodium sulfate, and filter. After the organic phase is spin dried, the residue is purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain 12.6mg of colorless oily liquid 3j with a yield of 45%.

[0089] The above reaction equation is as follows:

[0090]

[0091] 1 H NMR (500MHz, CDCl3) δ5.44(s,1H),3.68–3.58(m,2H),2.04–1.90(m,6H),1.71–1.64(m,2H),1.64–1.57(m,3H),1.57–1.50(m,2H);13 C NMR (126MHz, CDCl3) δ137.4,121.3,63.0,34.4,30.5,28.2,25.2,23.0,22.5.

[0092] Example 11 Synthesis of 3-(4-chlorophenyl)butan-1-ol

[0093] In a glove box filled with argon, 121.9 mg 2a (0.48 mmol, 2.4 equiv), 53.8 mg sodium trimethylsiloxy (0.48 mmol, 2.4 equiv), 12.7 mg ligand L13 (0.022 mmol, 11 mol%), and 4 mg catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed into a 25 mL Schlenk reaction tube, and then 2.0 mL tetrahydrofuran, 1k (0.2 mmol, 1.0 equiv) and 24 μL methanol (0.6 mmol, 3.0 equiv) were added. The stopcock was tightened and the mixture was placed in a heater preheated to 130° C. for 24 h.

[0094] After the reaction, add an appropriate amount of ethyl acetate to dilute the reaction solution, filter, remove the filter residue, collect the organic phase and spin dry, transfer the product to a round-bottom flask, add 2.0mL tetrahydrofuran, 1.0mL 30% H2O2 (aq) and 1.0mL 1mol / LNaOH (aq) and stir for 5h. After the reaction is completed by TLC detection, extract with ethyl acetate three times, dry with anhydrous sodium sulfate, and filter. After the organic phase is spin dried, the residue is purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain 3k 19.9mg colorless oily liquid, with a yield of 54%.

[0095] The above reaction equation is as follows:

[0096]

[0097] 1 H NMR(400MHz, CDCl3) δ7.26(d,J=8.5Hz,2H),7.13(d,J=8.5Hz,2H),3.60–3.48(m, 2H),2.93–2.84(m,1H),1.89–1.75(m,2H),1.32(br,s,1H),1.25(d,J=7.0Hz,3H); 13 CNMR (101MHz, CDCl3) δ145.3,131.7,128.6,128.3,60.9,40.8,35.8,22.3.

[0098] Example 12 Synthesis of 3-(4-(trifluoromethyl)phenyl)pentan-1-ol

[0099] In a glove box filled with argon, 121.9 mg 2a (0.48 mmol, 2.4 equiv), 53.8 mg sodium trimethylsiloxy (0.48 mmol, 2.4 equiv), 12.7 mg ligand L13 (0.022 mmol, 11 mol%), and 3 mg catalyst cuprous bromide (0.02 mmol, 10% mol%) were weighed into a 25 mL Schlenk reaction tube, and then 2.0 mL tetrahydrofuran was added, followed by 1 l (0.2 mmol, 1.0 equiv) and 56 μL tert-butanol (0.6 mmol, 3.0 equiv), the stopcock was tightened, and the tube was placed in a heater preheated to 130 ° C for 24 h.

[0100] After the reaction, add an appropriate amount of ethyl acetate to dilute the reaction solution, filter, remove the filter residue, collect the organic phase and spin dry, transfer the product to a round-bottom flask, add 2.0mL tetrahydrofuran, 1.0mL 30% H2O2 (aq) and 1.0mL 1mol / LNaOH (aq) and stir for 5h. After the reaction is completed by TLC detection, extract with ethyl acetate three times, dry with anhydrous sodium sulfate, and filter. After the organic phase is spin dried, the residue is purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain 31 32.0mg of colorless oily liquid, with a yield of 69%.

[0101] The above reaction equation is as follows:

[0102]

[0103] 1 H NMR (400MHz, CDCl3) δ7.52(d,J=7.9Hz,2H),7.25(d,J=8.0Hz,2H),3.54–3.36(m,2H),2.71–2.64(m,1H),2.01 –1.88(m,1H),1.81–1.74(m,1H),1.74–1.65(m,1H),1.63–1.53(m,1H),1.45(br,s,1H),0.75(t,J=7.4Hz,3H); 13 C NMR(101MHz,CDCl3)δ149.2,128.4(q, 2 J C-F =32.5Hz),128.0,125.3(q, 3 J C-F =3.9Hz),124.2(q, 1 J C-F=272.9Hz),60.7,43.9,38.9,29.5,11.9; 19 F NMR(376MHz, CDCl3)δ-62.31; HRMS(ESI-TOF)m / z Calcd forC 12 H 15 ONaF3[M+Na] + :231.0997,found:255.0973.

[0104] Example 13 Synthesis of 3-(4-chlorophenyl)-4-methylpentan-1-ol

[0105] In a glove box filled with argon, 121.9 mg 2a (0.48 mmol, 2.4 equiv), 53.8 mg sodium trimethylsiloxy (0.48 mmol, 2.4 equiv), 12.7 mg ligand L13 (0.022 mmol, 11 mol%), and 4 mg catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed into a 25 mL Schlenk reaction tube, and then 2.0 mL 1,4-dioxane, 1m (0.2 mmol, 1.0 equiv) and 24 μL methanol (0.6 mmol, 3.0 equiv) were added. The stopcock was tightened and the reaction was placed in a heater preheated to 130°C for 36 h.

[0106] After the reaction, add an appropriate amount of ethyl acetate to dilute the reaction solution, filter, remove the filter residue, collect the organic phase and spin dry, transfer the product to a round-bottom flask, add 2.0mL tetrahydrofuran, 1.0mL 30% H2O2 (aq) and 1.0mL 1mol / LNaOH (aq) and stir for 5h. After the reaction is completed by TLC detection, extract with ethyl acetate three times, dry with anhydrous sodium sulfate, and filter. After the organic phase is spin-dried, the residue is purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain a colorless oily liquid 3m 22.0mg, with a yield of 52%.

[0107] The above reaction equation is as follows:

[0108]

[0109] 1H NMR(400MHz, CDCl3)δ7.29–7.23(m,2H)7.12–7.02(m,2H),3.51–3.43(m,1H),3.42–3.32(m,1H),2.46–2.37 (m,1H),2.11–2.02(m,1H),1.84–1.72(m,2H),1.10(br,s,1H),0.96(d,J=6.3Hz,3H),0.72(d,J=6.7Hz,3H); 13 C NMR(101MHz, CDCl3)δ; 142.2,131.7,129.7,128.3,61.3,48.8,35.8,33.4,20.8,20.5; HRMS(ESI-TOF)m / z Calcd forC 12 H 17 ONaCl[M+Na] + :235.0866,found:235.0865.

[0110] Example 14 Synthesis of 3-(4-chlorophenyl)-3-cyclopropylpropan-1-ol

[0111] In a glove box filled with argon, 121.9 mg 2a (0.48 mmol, 2.4 equiv), 53.8 mg sodium trimethylsiloxy (0.48 mmol, 2.4 equiv), 12.7 mg ligand L13 (0.022 mmol, 11 mol%), and 4 mg catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed and placed in a 25 mL Schlenk reaction tube, and then 2.0 mL tetrahydrofuran, 1n (0.2 mmol, 1.0 equiv) and 28 μL tert-butyl alcohol (0.6 mmol, 3.0 equiv) were added. The stopcock was tightened and the mixture was placed in a heater preheated to 70°C for 24 h.

[0112] After the reaction, add an appropriate amount of ethyl acetate to dilute the reaction solution, filter, remove the filter residue, collect the organic phase and spin dry, transfer the product to a round-bottom flask, add 2.0mL tetrahydrofuran, 1.0mL 30% H2O2 (aq) and 1.0mL 1mol / LNaOH (aq) and stir for 5h. After TLC detection, extract with ethyl acetate three times, dry with anhydrous sodium sulfate, and filter. After the organic phase is spin dried, the residue is purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain 28.6mg of colorless oily liquid 3n with a yield of 68%.

[0113] The above reaction equation is as follows:

[0114]

[0115] 1 H NMR (400MHz, CDCl3) δ7.29–7.24(m,2H),7.19–7.10(m,2H),3.68–3.62(m,1H),3.58–3.48(m,1H),2.13–2.01(m,1H),2.01–1 .87(m,2H),1.19(br,s,1H),0.99–0.90(m,1H),0.68–0.54(m,1H),0.42–0.35(m,1H),0.29–0.23(m,1H),0.08–0.02(m,1H); 13 C NMR(126MHz, CDCl3)δ143.8,131.8,128.8,128.5,60.9,46.8,39.4,17.3,5.6,3.7; HRMS(ESI-TOF)m / z Calcd for C 12 H 14 Cl[M–OH] + :193.0779,found:193.0786.

[0116] Example 15 Synthesis of 3-cyclobutyl-3-phenylpropan-1-ol

[0117] In a glove box filled with argon, 121.9 mg 2a (0.48 mmol, 2.4 equiv), 53.8 mg sodium trimethylsiloxy (0.48 mmol, 2.4 equiv), 12.7 mg ligand L13 (0.022 mmol, 11 mol%), and 4 mg catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed into a 25 mL Schlenk reaction tube, and then 2.0 mL tetrahydrofuran, 1o (0.2 mmol, 1.0 equiv) and 56 μL tert-butyl alcohol (0.6 mmol, 3.0 equiv) were added. The stopcock was tightened and the mixture was placed in a heater preheated to 130° C. for 24 h.

[0118] After the reaction, add an appropriate amount of ethyl acetate to dilute the reaction solution, filter, remove the filter residue, collect the organic phase and spin dry, transfer the product to a round-bottom flask, add 2.0mL tetrahydrofuran, 1.0mL 30% H2O2 (aq) and 1.0mL 1mol / LNaOH (aq) and stir for 5h. After TLC detection, extract with ethyl acetate three times, dry with anhydrous sodium sulfate, and filter. After the organic phase is spin-dried, the residue is purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain 22.8mg of colorless oily liquid 3o with a yield of 60%.

[0119] The above reaction equation is as follows:

[0120]

[0121] 1 H NMR (400MHz, CDCl3) δ7.34–7.09(m,5H),3.59–3.35(m,2H),2.64–2.54(m,1H),2.52–2.44(m,1H) ),2.20–2.09(m,1H),2.04–1.89(m,1H),1.86–1.62(m,5H),1.60–1.53(m,1H),1.11(br,s,1H); 13 C NMR(126MHz, CDCl3)δ143.3,128.3,127.8,126.2,61.3,49.6,41.7,36.21,27.9,26.9,17.6; HRMS(ESI-TOF)m / z Calcd for C 13 H 18 ONa[M+Na] + :213.1255,found:213.1248.

[0122] Example 16 Synthesis of 3-cyclopentyl-3-phenylpropan-1-ol

[0123] In a glove box filled with argon, 121.9 mg 2a (0.48 mmol, 2.4 equiv), 53.8 mg sodium trimethylsiloxy (0.48 mmol, 2.4 equiv), 12.7 mg ligand L13 (0.022 mmol, 11 mol%), and 4 mg catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed into a 25 mL Schlenk reaction tube, and then 2.0 mL tetrahydrofuran, 1p (0.2 mmol, 1.0 equiv) and 34 μL ethanol (0.6 mmol, 3.0 equiv) were added. The stopcock was tightened and the reaction was placed in a heater preheated to 130° C. for 36 h.

[0124] After the reaction, add an appropriate amount of ethyl acetate to dilute the reaction solution, filter, remove the filter residue, collect the organic phase and spin dry, transfer the product to a round-bottom flask, add 2.0mL tetrahydrofuran, 1.0mL 30% H2O2 (aq) and 1.0mL 1mol / LNaOH (aq) and stir for 5h. After TLC detection, extract with ethyl acetate three times, dry with anhydrous sodium sulfate, and filter. After the organic phase is spin-dried, the residue is purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain 24.5mg of colorless oily liquid 3p with a yield of 60%.

[0125] The above reaction equation is as follows:

[0126]

[0127] 1 H NMR (400MHz, CDCl3) δ7.30–7.26(m,2H),7.21–7.12(m,3H),3.49–3.43(m, 1H),3.41–3.34(m,1H),2.47–2.37(m,1H),2.14–1.89(m,3H),1.85–1.74(m ,1H),1.71–1.62(m,1H),1.61–1.56(m,1H),1.56–1.51(m,1H),1.45–1.37( m,1H),1.36–1.30(m,1H),1.25(s,1H),1.12(br,s,1H),1.02–0.92(m,1H); 13 C NMR (126MHz, CDCl3) δ145.0,128.3,127.9,126.1,61.4,48.8,46.6,38.1,31.7,31.5,25.2,24.9.

[0128] Example 17 Synthesis of 3,3-diphenylpropan-1-ol

[0129] In a glove box filled with argon, 121.9 mg 2a (0.48 mmol, 2.4 equiv), 53.8 mg sodium trimethylsiloxy (0.48 mmol, 2.4 equiv), 12.7 mg ligand L13 (0.022 mmol, 11 mol%), and 4 mg catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed into a 25 mL Schlenk reaction tube, and then 2.0 mL tetrahydrofuran was added, followed by 1 q (0.2 mmol, 1.0 equiv) and 12 μL methanol (0.3 mmol, 1.5 equiv). The stopcock was tightened and the mixture was placed in a heater preheated to 70°C for 24 h.

[0130] After the reaction, add an appropriate amount of ethyl acetate to dilute the reaction solution, filter, remove the filter residue, collect the organic phase and spin dry, transfer the product to a round-bottom flask, add 2.0mL tetrahydrofuran, 1.0mL 30% H2O2 (aq) and 1.0mL 1mol / LNaOH (aq) and stir for 5h. After the reaction is completed by TLC detection, extract with ethyl acetate three times, dry with anhydrous sodium sulfate, and filter. After the organic phase is spin dried, the residue is purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain 3q 22.3mg colorless oily liquid, with a yield of 65%.

[0131] The above reaction equation is as follows:

[0132]

[0133] 1 H NMR (400MHz, CDCl3) δ7.31–7.25(m,8H),7.23–7.15(m,2H),4.17–4.11(m,1H),3.65–3.58(m,2H),2.36–2.29(m,2H),1.34(br,s,1H); 13 C NMR (101MHz, CDCl3) δ144.4,128.5,127.9,126.3,61.1,47.3,38.2.

[0134] Example 18 Synthesis of 4-(3-hydroxypropyl)ethyl benzoate

[0135] In a glove box filled with argon, 121.9 mg 2a (0.48 mmol, 2.4 equiv), 53.8 mg sodium trimethylsiloxy (0.48 mmol, 2.4 equiv), 13.2 mg ligand L1 (0.022 mmol, 11 mol%), and 4 mg catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed into a 25 mL Schlenk reaction tube, and then 2.0 mL tetrahydrofuran, 1r (0.2 mmol, 1.0 equiv) and 12 μL methanol (0.3 mmol, 1.5 equiv) were added. The stopcock was tightened and the mixture was placed in a heater preheated to 70°C for 24 h.

[0136] After the reaction, add an appropriate amount of ethyl acetate to dilute the reaction solution, filter, remove the filter residue, collect the organic phase and spin dry, transfer the product to a round-bottom flask, add 2.0mL tetrahydrofuran, 1.0mL 30% H2O2 (aq) and 1.0mL 1mol / LNaOH (aq) and stir for 5h. After the reaction is completed by TLC detection, extract with ethyl acetate three times, dry with anhydrous sodium sulfate, and filter. After the organic phase is spin dried, the residue is purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain 4.2mg of colorless oily liquid 3r with a yield of 10%.

[0137] The above reaction equation is as follows:

[0138]

[0139] 1 H NMR (400MHz, CDCl3) δ7.96(d,J=8.1Hz,2H),7.26(d,J=8.1Hz,2H),4.36(q,J=7.2Hz,2H),3.7 1–3.64(m,2H),2.82–2.72(m,2H),1.96–1.86(m,2H),1.59(br,s,1H),1.39(t,J=7.2Hz,3H); 13 C NMR (101MHz, CDCl3) δ166.7,147.3,129.7,128.4,128.2,62.0,60.8,33.8,32.1,14.3.

[0140] The embodiments described above are only preferred embodiments of the present invention and are only used to explain the present invention, not to limit the scope of implementation of the present invention. For those skilled in the art, other implementation methods can certainly be easily made by replacement or modification based on the technical contents disclosed in this specification. Therefore, all changes and improvements made on the principles of the present invention should be included in the scope of the patent application of the present invention.

Claims

1. A method for synthesizing alkyl borate compounds using allyl alcohol as a substrate, characterized in that: The following steps are involved: Using allyl alcohol and biboric acid pinacol ester as substrates and monovalent copper salt as catalyst, in the presence of a base, a proton source and a ligand, an alkyl borate compound as shown in formula II is obtained by reacting in an organic solvent according to the following reaction formula; Wherein: R1 is selected from hydrogen, C1-C3 alkyl, C3-C6 cycloalkyl, phenyl; R2 is selected from phenyl arbitrarily substituted at the para, ortho or meta position, condensed ring aromatic group, five-membered heterocyclic group, cyclohexyl, substituted cyclohexyl or cyclohexenyl, and the substituent on the aromatic group is selected from halogen, trifluoromethyl, C1-C3 alkoxy, phenyl.

2. The method according to claim 1, characterized in that: The monovalent copper salt is selected from cuprous chloride, cuprous iodide or cuprous bromide.

3. The method according to claim 1, characterized in that: The base is selected from one of sodium trimethylsiloxy, potassium tert-butoxide or sodium ethoxide.

4. The method according to claim 1, characterized in that The proton source is selected from one of tert-butyl alcohol, methanol and ethanol.

5. The method according to claim 1, characterized in that The ligand is 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene.

6. The method according to claim 1, characterized in that The organic solvent is selected from one of 1,4-dioxane, tetrahydrofuran or methyl tert-butyl ether.

7. The method according to claim 1, characterized in that The molar amount of the monovalent copper salt is 5-20% of the molar amount of the allyl alcohol shown in formula I.

8. The method according to claim 1, characterized in that The molar amount of the ligand is 10-15% of the molar amount of the allyl alcohol shown in formula I.

9. The method according to claim 1, characterized in that: The molar amount of the proton source is 2 to 3 times the molar amount of the allyl alcohol shown in formula I.

10. The method according to claim 1, characterized in that The molar ratio of the allyl alcohol represented by the formula I to the bipyraclostrobin is 1:2-4.

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