Method for synthesizing alkyl borate compounds using allyl alcohol as a substrate

Abstract

The application belongs to the technical field of organic synthesis, and discloses a method for synthesizing alkyl borate compounds by taking allyl alcohol as a substrate, which comprises the following steps: taking allyl alcohol shown in formula I and pinacol diboron as substrates, taking monovalent copper salt as a catalyst, and reacting in an organic solvent under the action of a base, a proton source and a ligand to obtain alkyl borate compounds shown in formula II according to the following reaction formula. In the application, monovalent copper is used to catalyze the coupling of pinacol diboron and allyl alcohol to form alkyl borate, the substrate range is widened, the use of noble metals and strong reducing agents is avoided, no excess metal waste is generated, the green chemistry concept is met, the reaction steps are significantly shortened, and the cost can be reduced.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of organic synthesis, and relates to a method for synthesizing an alkyl borate compound by taking an allyl alcohol as a substrate. BACKGROUND

[0002] Organoboron compounds have been widely used in many fields such as organic synthesis, catalysis, drug discovery and material science. In recent years, material chemists have found that organoboron compounds can also be used as ideal components or precursors of conjugated materials, covalent organic frameworks and hydrogels. In addition, they can also be used as an important class of synthons, which can be used in transition metal-catalyzed cross-coupling reactions and other functional group transformations to introduce different chemical groups. At present, alkyl borates 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 and borate, which has a high yield, but this method cannot be used for aromatic halides with ester groups, cyano groups, nitro groups, carbonyl groups and other functional groups in the molecule, which limits the range of substrates (reference: Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457).

[0004] (2) Metal-catalyzed boronation of halogenated hydrocarbons: Ishiyama and Miyaura first reported the boronation reaction of organic halides in 2000 and achieved great development, but such reactions need to use halogenated hydrocarbons, and some need to use noble metal catalysts, which causes environmental pollution and waste of resources, and is 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 reaction: since 1985 After the transition metal Rh-catalyzed hydroboration reaction of pinacolborane (i.e. o-benzenedioxaborane) with olefins was first realized in 1985, great achievements have been made in the hydroboration of olefins, realizing the transition metal-catalyzed hydroboration of copper, nickel, iron, cobalt and other transition metals as well as non-transition metal-catalyzed hydroboration of olefins for the construction of alkyl boron. However, it still has defects, and there are still great difficulties in the preparation of some olefin raw materials, which increases the cost of such reactions and reduces the 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 borylation of alkenes: After the first example of metal rhodium-catalyzed borylation of internal alkenes was achieved by Marder group in 1998, Miura, Nakao, Brown and other groups made outstanding contributions in the study of borylation of 1,2-bifunctionalization. Especially, recently, Professor Keary Engle group achieved the regioselective carbo- and aminoboration of non-conjugated alkenes using Pd catalyst, which was the first example of Pd(II)-catalyzed borylation of alkenes. But the shortcoming is that noble metal palladium is used as catalyst, and the scope of substrates is limited (Ref: Zhen, L.; Hui-Qi, N.; Tian, Z.; Keary M., E. Catalytic Carbo- and Aminoboration of Alkenyl Carbonyl Compounds via Five- and Six-Membered Palladacycles. J. Am. Chem. Soc. 2018, 140, 3223-3227).

[0007] (5) Transition-metal-catalyzed borylation of C-H bond: In 2013, Hartwig group reported iridium-catalyzed borylation of benzylic C-H bond. In addition, the borylation of heteroatom alpha C-H, allylic C-H and non-activated C(sp 3 )-H bond has been very in-depth. But the common shortcoming is that it relies on the use of directing groups to ensure the interaction of noble metal catalyst and reactants to achieve the borylation of C-H bond, which leads to the limited scope of substrates (Ref: Seung, H. C. and John, F. H. Iridium-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 very important application value in various fields, but the current method has certain limitations in synthesizing alkyl borate compounds, not only the scope of substrates is limited, but also the atom economy is low. Therefore, it is of great significance to develop a new method for preparing alkyl borate compounds. SUMMARY

[0009] The present application aims at the above technical problems, and provides a method for synthesizing alkyl borate compounds by taking allyl alcohol as a substrate, which adopts monovalent copper to catalyze the coupling of pinacol diboron and allyl alcohol to form alkyl borate, widens the substrate range, avoids the use of noble metals and strong reducing agents, does not produce excess metal waste, accords with the green chemistry concept, significantly shortens the reaction steps, and can reduce the cost.

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

[0011] The present application provides a method for synthesizing alkyl borate compounds by taking allyl alcohol as a substrate, which comprises the following steps: taking allyl alcohol and pinacol diboron as substrates, taking monovalent copper salt as a catalyst, and reacting in an organic solvent under the action of a base, a proton source and a ligand to obtain an alkyl borate compound represented by formula II according to the following reaction formula.

[0012]

[0013] wherein: R1 is selected from hydrogen, C1-C3 alkyl, C3-C6 cycloalkyl and phenyl; R2 is selected from para-, ortho- or meta-substituted phenyl, fused ring aryl, five-membered heterocyclic group, cyclohexane group, substituted cyclohexane group or cyclohexene group, and the substituents on the phenyl are selected from halogen, trifluoromethyl, C1-C3 alkoxy and phenyl.

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

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

[0016] In the above technical solution, the proton source is selected from one of tert-butanol, methanol and ethanol.

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

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

[0019] In the above technical solution, the molar amount of the monovalent copper salt is 5-20% of the molar amount of the allyl alcohol represented by formula I.

[0020] In the above technical solution, the molar amount of the ligand is 10-15% of the molar amount of the allyl alcohol represented by formula I.

[0021] In the above technical solution, the molar amount of the proton source is 2-3 times of the molar amount of the allyl alcohol represented by formula I.

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

[0023] The molar amount of the base in the technical solution is 2-4 times the molar amount of the allyl alcohol represented by Formula I.

[0024] The amount of the organic solvent in the technical solution is 10 mL-30 mL of the organic solvent per mmol of the allyl alcohol represented by Formula I.

[0025] The reaction temperature in the technical solution is 70 DEG C, and the reaction time is 24 h.

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

[0027] 1. The present application uses monovalent copper to catalyze the coupling of pinacol diboron and allyl alcohol to form alkyl borate, which widens the substrate range, avoids the use of noble metals and strong reducing agents, does not produce excess metal waste, conforms to the concept of green chemistry, significantly shortens the reaction steps, and can reduce costs.

[0028] 2. The present application 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, and the alkyl borate is unstable and is oxidized to alcohol in one step, which also widens the synthesis of alcohol compounds.

[0029] 3. The raw materials in the present application are cheap and easy to obtain, the operation is simple and safe, the conditions are mild, the reaction yield is high, and the industrial production is easy to realize. DETAILED DESCRIPTION

[0030] The following examples are used to illustrate the present application, but are not used to limit the protection scope of the present application. If not specifically indicated, the technical means used in the examples is the 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 pinacol diboron, L13 represents 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, and L1 represents (9,9-dimethyl-9H-fluorene-4,5-diyl)bis(dicyclohexylphosphane).

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

[0033] In an argon filled glove box, 121.9 mg of 2a (0.48 mmol, 2.4 equiv), 53.8 mg of sodium trimethylsilanolate (0.48 mmol, 2.4 equiv), 12.7 mg of ligand L13 (0.022 mmol, 11 mol%), 4 mg of catalyst copper(I) iodide (0.02 mmol, 10 mol%) were weighed into a 25 mL Schlenk tube, followed by the addition of 2.0 mL of 1,4-dioxane, then 1a (0.2 mmol, 1.0 equiv) and 28 μL of t-butanol (0.3 mmol, 1.5 equiv). The cap was tightened and the Schlenk tube was placed in a pre-heated heater at 70 °C for 24 h.

[0034] After the reaction was complete, the reaction was diluted with an appropriate amount of ethyl acetate, filtered to remove the filter residue, the organic phase was collected and rotary evaporated, the product was transferred to a round bottom flask, 2.0 mL of tetrahydrofuran, 1.0 mL of 30% H2O2(aq) and 1.0 mL of 1 mol / L NaOH(aq) were added and stirred for 5 h, after the reaction was complete as detected by TLC, the product was extracted with ethyl acetate three times, dried over anhydrous sodium sulfate and filtered. The organic phase was rotary evaporated and the residue was purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to give the product 3a as a colorless oily liquid 21.1 mg in 62% yield.

[0035] The above reaction scheme is as follows:

[0036]

[0037] 1 H NMR (400 MHz, CDC13) δ 7.27 - 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 (101 MHz, CDC13) δ 140.3, 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 an argon-filled glove box, 121.9 mg of 2a (0.48 mmol, 2.4 equiv), 53.8 mg of sodium trimethylsilanide (0.48 mmol, 2.4 equiv), 12.7 mg of ligand L13 (0.022 mmol, 11 mol%), 4 mg of catalyst cuprous iodide (0.02 mmol, 10 mol%) were weighed into a 25 mL Schlenk tube, then 2.0 mL of tetrahydrofuran was added, followed by 1b (0.2 mmol, 1.0 equiv) and 12 μL of methanol (0.3 mmol, 1.5 equiv). Tighten the plug, and place it in a heater preheated to 70°C for 24 h.

[0040] After the reaction was completed, the reaction solution was diluted with an appropriate amount of ethyl acetate, filtered to remove the filter residue, and the organic phase was collected and rotary evaporated. The product was transferred to a round-bottom flask, 2.0 mL of tetrahydrofuran, 1.0 mL of 30% H2O2(aq) and 1.0 mL of 1 mol / L NaOH(aq) were added and stirred for 5 h. After the reaction was completed, TLC detection was performed, and the product was extracted with ethyl acetate three times, dried over anhydrous sodium sulfate, and filtered. After the organic phase was rotary evaporated, the residue was purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as the eluent to obtain colorless oily liquid 3b 26.1 mg, yield 64%.

[0041] The above reaction equation is as follows:

[0042]

[0043] 1 H NMR (400 MHz, CDC13) δ 7.54 (d, J = 6.4 Hz, 2H), 7.31 (d, J = 6.4 Hz, 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 (126 MHz, CDC13) δ 146.0, 128.7, 128.5 (q, J = 32.8 Hz), 125.3 (q, J = 272.2 Hz), 61.9, 33.8, 31.9; 2 J C-F = 32.8 Hz), 125.3 (q, J = 272.2 Hz), 61.9, 33.8, 31.9; 3 J C-F = 32.8 Hz), 125.3 (q, J = 272.2 Hz), 61.9, 33.8, 31.9; 1 J C-F = 32.8 Hz), 125.3 (q, J = 272.2 Hz), 61.9, 33.8, 31.9; 19 F NMR (376 MHz, CDC13) δ -62.32.

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

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

[0046] After the reaction was completed, the reaction solution was diluted with an appropriate amount of ethyl acetate, filtered to remove the filter residue, and the organic phase was collected and rotary evaporated. The product was transferred to a round-bottom flask, 2.0 mL of tetrahydrofuran, 1.0 mL of 30% H2O2(aq) and 1.0 mL of 1 mol / L NaOH(aq) were added, and stirred for 5 h. After the reaction was completed, the reaction solution was extracted with ethyl acetate three times, dried over anhydrous sodium sulfate, and filtered. The organic phase was rotary evaporated, and the residue was purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as the eluent to obtain 21.6 mg of colorless oily liquid 3c with a yield of 65%.

[0047] The above reaction equation is as follows:

[0048]

[0049] 1 H NMR (400 MHz, CDCl3) δ 7.15-7.08 (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 (101 MHz, CDCl3) δ 157.8, 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 an argon-filled glove box, 121.9 mg of 2a (0.48 mmol, 2.4 equiv), 53.8 mg of potassium tert-butoxide (0.48 mmol, 2.4 equiv), 12.7 mg of ligand L13 (0.022 mmol, 11 mol%), 4 mg of catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed into a 25 mL Schlenk tube, then 2.0 mL of tetrahydrofuran was added, followed by 1d (0.2 mmol, 1.0 equiv) and 12 μL of methanol (0.3 mmol, 1.5 equiv). Tighten the plug, and place it in a heater preheated to 70°C for 24 h.

[0052] After the reaction was completed, the reaction solution was diluted with an appropriate amount of ethyl acetate, filtered to remove the filter residue, and the organic phase was collected and rotary evaporated. The product was transferred to a round-bottom flask, 2.0 mL of tetrahydrofuran, 1.0 mL of 30% H2O2(aq) and 1.0 mL of 1 mol / L NaOH(aq) were added and stirred for 5 h. After TLC detection, the reaction was completed, extracted with ethyl acetate three times, dried over anhydrous sodium sulfate, and filtered. After rotary evaporation of the organic phase, the residue was purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain colorless oily liquid 3d 24.2 mg, yield 53%.

[0053] The above reaction equation is as follows:

[0054]

[0055] 1 H NMR (400 MHz, CDC13) δ 7.37 - 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 (101 MHz, CDC13) δ 157.27, 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 an argon-filled glove box, 121.9 mg of 2a (0.48 mmol, 2.4 equiv), 53.8 mg of sodium trimethylsiloxy (0.48 mmol, 2.4 equiv), 12.7 mg of ligand L13 (0.022 mmol, 11 mol%), and 2 mg of catalyst cuprous chloride (0.02 mmol, 10% mol%) were weighed sequentially and placed into a 25 mL Schlenk reaction tube. Then, 2.0 mL of tetrahydrofuran was added, followed by 1e (0.2 mmol, 1.0 equiv) and 12 μL of methanol (0.3 mmol, 1.5 equiv). The stopcock was tightened, and the tube was placed in a heater preheated to 70 °C for 24 h.

[0058] After the reaction was complete, the reaction solution was diluted with an appropriate amount of ethyl acetate, filtered, the residue was removed, the organic phase was collected and evaporated to dryness, the product was transferred to a round-bottom flask, 2.0 mL of tetrahydrofuran, 1.0 mL of 30% H2O2 (aq) and 1.0 mL of 1 mol / L NaOH (aq) were added, and the mixture was stirred for 5 h. After the reaction was completed by TLC, the product was extracted three times with ethyl acetate, dried over anhydrous sodium sulfate, and filtered. After the organic phase was evaporated to dryness, the residue was purified by silica gel column chromatography using petroleum ether:ethyl acetate (10:1) as the eluent to give a colorless oily liquid 3e 24.0 mg, yield 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)prop-1-ol

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

[0064] After the reaction was completed, the reaction solution was diluted with an appropriate amount of ethyl acetate, filtered, and the filtrate was collected and dried. The product was transferred to a round-bottom flask, 2.0 mL of tetrahydrofuran, 1.0 mL of 30% H2O2(aq) and 1.0 mL of 1 mol / L NaOH(aq) were added, and stirred for 5 h. After the reaction was completed, the reaction solution was extracted with ethyl acetate three times, dried over anhydrous sodium sulfate, and filtered. The organic phase was dried, and the residue was purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as the eluent to obtain 3f 32.9 mg as a colorless oily liquid, with a yield of 60%.

[0065] The above reaction equation is as follows:

[0066]

[0067] 1 H NMR (400 MHz, CDC13) δ 6.98 (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 (101 MHz, CDC13) δ 148.3, 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-(naphthalen-2-yl)propan-1-ol

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

[0070] After the reaction was completed, an appropriate amount of ethyl acetate was added to dilute the reaction solution, filtered to remove the filter residue, and the organic phase was collected and rotary evaporated. The product was transferred to a round-bottom flask, 2.0 mL of tetrahydrofuran, 1.0 mL of 30% H2O2(aq) and 1.0 mL of 1 mol / L NaOH(aq) were added and stirred for 5 h. After TLC detection, the reaction was completed, extracted with ethyl acetate three times, dried over anhydrous sodium sulfate, and filtered. After the organic phase was rotary evaporated, the residue was purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain colorless oily liquid 3g 31.0 mg, yield 85%.

[0071] The above reaction equation is as follows:

[0072]

[0073] 1 H NMR (400 MHz, CDC13) δ 7.82-7.77 (m, 3H), 7.65 (s, 1H), 7.48-7.41 (m, 2H), 7.38-7.33 (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 (101 MHz, CDC13) δ 139.3, 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 an argon-filled glove box, 121.9 mg of 2a (0.48 mmol, 2.4 equiv), 53.8 mg of sodium trimethylsilanolate (0.48 mmol, 2.4 equiv), 12.7 mg of ligand L13 (0.022 mmol, 11 mol%), 4 mg of catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed into a 25 mL Schlenk tube, then 2.0 mL of tetrahydrofuran was added, followed by 1h (0.2 mmol, 1.0 equiv) and 12 μL of methanol (0.3 mmol, 1.5 equiv). Tighten the plug, and place it in a heater preheated to 70°C for 24h.

[0076] After the reaction was completed, the reaction solution was diluted with an appropriate amount of ethyl acetate, filtered, the filtrate was collected, and the organic phase was dried and concentrated. The product was transferred to a round-bottom flask, 2.0 mL of tetrahydrofuran, 1.0 mL of 30% H2O2(aq) and 1.0 mL of 1 mol / L NaOH(aq) were added, and stirred for 5h. After the reaction was completed by TLC detection, it was extracted with ethyl acetate three times, dried over anhydrous sodium sulfate, and filtered. After the organic phase was concentrated, the residue was purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain colorless oily liquid 3h 29.8 mg, yield 56%.

[0077] The above reaction equation is as follows:

[0078]

[0079] 1 H NMR (400 MHz, CDC13) δ 6.69 (dd, J = 7.8, 1.9 Hz, 1H), 6.52 (dd, J = 7.8, 1.9 Hz, 1H), 6.47 (dd, J = 7.8, 1.9 Hz, 1H), 6.44 - 6.42 (m, 2H), 6.40 (dd, J = 7.9, 1.9 Hz, 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 - 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 (101 MHz, CDC13) δ 141.1, 139.8, 139.4, 137.5, 134.8, 134.6, 133.3, 133.1, 132.1, 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 an argon-filled glove box, 121.9 mg of 2a (0.48 mmol, 2.4 equiv), 32.7 mg of sodium ethoxide (0.48 mmol, 2.4 equiv), 12.7 mg of ligand L13 (0.022 mmol, 11 mol%), 4 mg of catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed in a 25 mL Schlenk tube, then 2.0 mL of tetrahydrofuran was added, followed by 1i (0.2 mmol, 1.0 equiv) and 28 μL of tert-butyl alcohol (0.3 mmol, 1.5 equiv). The cap was screwed tightly, and the Schlenk tube was placed in a preheated heater at 70 °C for 24 h.

[0082] After the reaction was completed, the reaction solution was diluted with an appropriate amount of ethyl acetate, filtered to remove the filter residue, and the organic phase was collected and rotary evaporated. The product was transferred to a round-bottom flask, 2.0 mL of tetrahydrofuran, 1.0 mL of 30% H2O2(aq) and 1.0 mL of 1 mol / L NaOH(aq) were added, and stirred for 5 h. After the reaction was completed, the reaction solution was extracted with ethyl acetate three times, dried over anhydrous sodium sulfate, and filtered. The organic phase was rotary evaporated, and the residue was purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain 3i as a colorless oily liquid, 15.4 mg, yield 61%.

[0083] The above reaction equation is as follows:

[0084]

[0085] 1H NMR (400 MHz, CDC13) δ 7.33 - 7.28 (m, 1H), 6.31 - 6.25 (m, 1H), 6.01 (dd, J = 3.1, 0.9 Hz, 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 (101 MHz, CDC13) δ 155.5, 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 an argon-filled glove box, 121.9 mg of 2a (0.48 mmol, 2.4 equiv), 53.8 mg of sodium trimethylsilanolate (0.48 mmol, 2.4 equiv), 12.7 mg of ligand L13 (0.022 mmol, 11 mol%), 4 mg of catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed into a 25 mL Schlenk tube, then 2.0 mL of 1,4-dioxane was added, followed by 1j (0.2 mmol, 1.0 equiv) and 56 μL of t-butanol (0.6 mmol, 3.0 equiv). The cap was screwed tightly, and the Schlenk tube was placed in a preheated 130 °C heater for 36 h.

[0088] After the reaction was completed, the reaction solution was diluted with an appropriate amount of ethyl acetate, filtered to remove the filter residue, and the organic phase was collected and rotary evaporated. The product was transferred to a round-bottom flask, 2.0 mL of tetrahydrofuran, 1.0 mL of 30% H2O2(aq) and 1.0 mL of 1 mol / L NaOH(aq) were added and stirred for 5 h. After the reaction was completed, as detected by TLC, it was extracted with ethyl acetate three times, dried over anhydrous sodium sulfate, and filtered. After the organic phase was rotary evaporated, the residue was purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as the eluent to obtain 3j 12.6 mg as a colorless oily liquid, with a yield of 45%.

[0089] The above reaction equation is as follows:

[0090]

[0091] 1 H NMR (400 MHz, CDC13) δ 7.33 - 7.28 (m, 1H), 6.31 - 6.25 (m, 1H), 6.01 (dd, J = 3.1, 0.9 Hz, 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 C NMR (126 MHz, CDC13) δ 137.4, 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 an argon-filled glove box, 121.9 mg of 2a (0.48 mmol, 2.4 equiv), 53.8 mg of sodium trimethylsilanolate (0.48 mmol, 2.4 equiv), 12.7 mg of ligand L13 (0.022 mmol, 11 mol%), 4 mg of catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed into a 25 mL Schlenk tube, followed by the addition of 2.0 mL of tetrahydrofuran, 1 k (0.2 mmol, 1.0 equiv) and 24 μL of methanol (0.6 mmol, 3.0 equiv). The cap was screwed tightly, and the Schlenk tube was placed in a preheated heater at 130 °C for 24 h.

[0094] After the reaction was completed, the reaction solution was diluted with an appropriate amount of ethyl acetate, filtered to remove the filter residue, and the organic phase was collected and rotary evaporated. The product was transferred to a round-bottom flask, 2.0 mL of tetrahydrofuran, 1.0 mL of 30% H2O2(aq) and 1.0 mL of 1 mol / L NaOH(aq) were added, and stirred for 5 h. After the reaction was completed, as detected by TLC, it was extracted with ethyl acetate three times, dried over anhydrous sodium sulfate, and filtered. After the organic phase was rotary evaporated, the residue was purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as the eluent to obtain 3k 19.9 mg as a colorless oily liquid, with a yield of 54%.

[0095] The above reaction equation is as follows:

[0096]

[0097] 1 H NMR (400 MHz, CDC13) δ 7.26 (d, J = 8.5 Hz, 2H), 7.13 (d, J = 8.5 Hz, 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 = 7.0 Hz, 3H); 13 CNMR (101 MHz, CDC13) δ 145.3, 131.7, 128.6, 128.3, 60.9, 40.8, 35.8, 22.3.

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

[0099] In an argon-filled glove box, 121.9 mg of 2a (0.48 mmol, 2.4 equiv), 53.8 mg of sodium trimethylsiloxy (0.48 mmol, 2.4 equiv), 12.7 mg of ligand L13 (0.022 mmol, 11 mol%), and 3 mg of catalyst cuprous bromide (0.02 mmol, 10% mol%) were weighed sequentially and placed into a 25 mL Schlenk reaction tube. Then, 2.0 mL of tetrahydrofuran was added, followed by 1 L (0.2 mmol, 1.0 equiv) and 56 μL of 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 was complete, the reaction solution was diluted with an appropriate amount of ethyl acetate, filtered, the residue was removed, the organic phase was collected and evaporated to dryness, the product was transferred to a round-bottom flask, 2.0 mL of tetrahydrofuran, 1.0 mL of 30% H2O2 (aq) and 1.0 mL of 1 mol / L NaOH (aq) were added, and the mixture was stirred for 5 h. After the reaction was completed by TLC, the product was extracted three times with ethyl acetate, dried over anhydrous sodium sulfate, and filtered. After the organic phase was evaporated to dryness, the residue was purified by silica gel column chromatography using petroleum ether:ethyl acetate (10:1) as the eluent to give 3 l (32.0 mg) of a 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= 272.9 Hz), 60.7, 43.9, 38.9, 29.5, 11.9; 19 F NMR (376 MHz, CDCl3) δ -62.31; HRMS (ESI-TOF) m / z Calcd for C 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 an argon-filled glove box, 121.9 mg of 2a (0.48 mmol, 2.4 equiv), 53.8 mg of sodium trimethylsilanolate (0.48 mmol, 2.4 equiv), 12.7 mg of ligand L13 (0.022 mmol, 11 mol%), 4 mg of catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed into a 25 mL Schlenk tube, followed by the addition of 2.0 mL of 1,4-dioxane, 1 m (0.2 mmol, 1.0 equiv) and 24 μL of methanol (0.6 mmol, 3.0 equiv). The cap was screwed tightly, and the Schlenk tube was placed in a preheated heater at 130 °C for 36 h.

[0106] After the reaction was completed, the reaction solution was diluted with an appropriate amount of ethyl acetate, filtered to remove the filter residue, and the organic phase was collected and rotary evaporated. The product was transferred to a round-bottom flask, 2.0 mL of tetrahydrofuran, 1.0 mL of 30% H2O2(aq) and 1.0 mL of 1 mol / L NaOH(aq) were added, and stirred for 5 h. After the reaction was completed, as detected by TLC, it was extracted with ethyl acetate three times, dried over anhydrous sodium sulfate, and filtered. After the organic phase was rotary evaporated, the residue was purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as the eluent to obtain 3m 22.0 mg of colorless oily liquid with a yield of 52%.

[0107] The above reaction equation is as follows:

[0108]

[0109] 1H NMR (400 MHz, CDC13) δ 7.29 - 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 = 6.3 Hz, 3H), 0.72 (d, J = 6.7 Hz, 3H); 13 C NMR (101 MHz, CDC13) 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 for C 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 the glove box filled with argon, 121.9 mg of 2a (0.48 mmol, 2.4 equiv), 53.8 mg of sodium trimethylsilanolate (0.48 mmol, 2.4 equiv), 12.7 mg of ligand L13 (0.022 mmol, 11 mol%), 4 mg of catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed in a 25 mL Schlenk reactor, then 2.0 mL of tetrahydrofuran was added, followed by 1 n (0.2 mmol, 1.0 equiv) and 28 μL of tert-butyl alcohol (0.6 mmol, 3.0 equiv). Tighten the plug, place it in a heater preheated to 70°C for 24h.

[0112] After the reaction was completed, the reaction solution was diluted with an appropriate amount of ethyl acetate, filtered to remove the filter residue, and the organic phase was collected and rotary evaporated. The product was transferred to a round-bottom flask, 2.0 mL of tetrahydrofuran, 1.0 mL of 30% H2O2(aq) and 1.0 mL of 1 mol / L NaOH(aq) were added and stirred for 5h. After the reaction was completed by TLC detection, it was extracted with ethyl acetate three times, dried over anhydrous sodium sulfate, and filtered. After the organic phase was rotary evaporated, the residue was purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as eluent to obtain colorless oily liquid 3n 28.6 mg, yield 68%.

[0113] The above reaction equation is as follows:

[0114]

[0115] 1 H NMR (400 MHz, CDC13) δ 7.29 - 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 (126 MHz, CDC13) δ 143.8, 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 an argon-filled glove box, 121.9 mg of 2a (0.48 mmol, 2.4 equiv), 53.8 mg of sodium trimethylsilanolate (0.48 mmol, 2.4 equiv), 12.7 mg of ligand L13 (0.022 mmol, 11 mol%), 4 mg of catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed into a 25 mL Schlenk reaction tube, followed by the addition of 2.0 mL of tetrahydrofuran, followed by the addition of 1o (0.2 mmol, 1.0 equiv) and 56 μL of t-butanol (0.6 mmol, 3.0 equiv). The cap was tightened, and the reaction tube was placed in a preheated 130 °C heater for 24 h.

[0118] After the reaction was completed, the reaction solution was diluted with an appropriate amount of ethyl acetate, filtered to remove the filter residue, and the organic phase was collected and rotary evaporated. The product was transferred to a round-bottom flask, 2.0 mL of tetrahydrofuran, 1.0 mL of 30% H2O2(aq) and 1.0 mL of 1 mol / L NaOH(aq) were added and stirred for 5 h. After the reaction was completed, as detected by TLC, it was extracted with ethyl acetate three times, dried over anhydrous sodium sulfate, and filtered. After the organic phase was rotary evaporated, the residue was purified by silica gel column chromatography using petroleum ether: ethyl acetate (10:1) as the eluent to obtain 3o as a colorless oily liquid 22.8 mg in a yield of 60%.

[0119] The above reaction equation is as follows:

[0120]

[0121] 1 H NMR (400 MHz, CDC13) δ 7.34 - 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 (126 MHz, CDC13) δ 143.3, 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 an argon-filled glove box, 121.9 mg of 2a (0.48 mmol, 2.4 equiv), 53.8 mg of sodium trimethylsilanolate (0.48 mmol, 2.4 equiv), 12.7 mg of ligand L13 (0.022 mmol, 11 mol%), 4 mg of catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed in sequence into a 25 mL Schlenk reaction tube, then 2.0 mL of tetrahydrofuran was added, followed by the addition of 1p (0.2 mmol, 1.0 equiv) and 34 μL of ethanol (0.6 mmol, 3.0 equiv). The cap was tightened, and the reaction tube was placed in a preheated heater at 130 °C for 36 h.

[0124] After the reaction was completed, an appropriate amount of ethyl acetate was added to dilute the reaction solution, filtered to remove the filter residue, the organic phase was collected and rotary evaporated, the product was transferred to a round-bottom flask, 2.0 mL of tetrahydrofuran, 1.0 mL of 30% H2O2(aq) and 1.0 mL of 1 mol / L NaOH(aq) were added and stirred for 5 h, after TLC detection of the end of the reaction, extracted with ethyl acetate three times, dried over anhydrous sodium sulfate and filtered. After the organic phase was rotary evaporated, the residue was purified by silica gel column chromatography using petroleum ether: ethyl acetate (10: 1) as eluent to obtain colorless oily liquid 3p 24.5 mg, yield 60%.

[0125] The above reaction equation is as follows:

[0126]

[0127] 1 H NMR (400 MHz, CDCl3) δ 7.30-7.26 (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 (126 MHz, CDCl3) δ 145.0, 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 an argon-filled glove box, 121.9 mg of 2a (0.48 mmol, 2.4 equiv), 53.8 mg of sodium trimethylsilanolate (0.48 mmol, 2.4 equiv), 12.7 mg of ligand L13 (0.022 mmol, 11 mol%), 4 mg of catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed in sequence into a 25 mL Schlenk reaction tube, then 2.0 mL of tetrahydrofuran was added, followed by the addition of 1q (0.2 mmol, 1.0 equiv) and 12 μL of methanol (0.3 mmol, 1.5 equiv). Tighten the plug, place it in a preheated to 70°C heater for 24 h.

[0130] After the reaction was completed, the reaction solution was diluted with an appropriate amount of ethyl acetate, filtered to remove the filter residue, the organic phase was collected and rotary evaporated, the product was transferred to a round-bottom flask, 2.0 mL of tetrahydrofuran, 1.0 mL of 30% H2O2(aq) and 1.0 mL of 1 mol / L NaOH(aq) were added, stirred for 5 h, after TLC detection of the end of the reaction, extracted with ethyl acetate three times, dried over anhydrous sodium sulfate and filtered. After the organic phase was rotary evaporated, the residue was purified by silica gel column chromatography using petroleum ether: ethyl acetate (10: 1) as eluent to obtain colorless oily liquid 3q 22.3 mg, yield 65%.

[0131] The above reaction equation is as follows:

[0132]

[0133] 1 H NMR (400 MHz, CDC13) δ 7.31 - 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 (101 MHz, CDC13) δ 144.4, 128.5, 127.9, 126.3, 61.1, 47.3, 38.2.

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

[0135] In an argon-filled glove box, 121.9 mg of 2a (0.48 mmol, 2.4 equiv), 53.8 mg of sodium trimethylsilanolate (0.48 mmol, 2.4 equiv), 13.2 mg of ligand L1 (0.022 mmol, 11 mol%), 4 mg of catalyst cuprous iodide (0.02 mmol, 10% mol%) were weighed in sequence into a 25 mL Schlenk reaction tube, then 2.0 mL of tetrahydrofuran was added, followed by the addition of 1r (0.2 mmol, 1.0 equiv) and 12 μL of methanol (0.3 mmol, 1.5 equiv). Tighten the plug, place it in a preheated to 70°C heater and react for 24 h.

[0136] After the reaction was completed, the reaction solution was diluted with an appropriate amount of ethyl acetate, filtered to remove the filter residue, the organic phase was collected and rotary evaporated, the product was transferred to a round bottom flask, 2.0 mL of tetrahydrofuran, 1.0 mL of 30% H2O2(aq) and 1.0 mL of 1 mol / L NaOH(aq) were added and stirred for 5 h, after the reaction was completed by TLC detection, it was extracted with ethyl acetate three times, dried over anhydrous sodium sulfate and filtered. After the organic phase was rotary evaporated, the residue was purified by silica gel column chromatography using petroleum ether: ethyl acetate (10: 1) as eluent to obtain colorless oily liquid 3r 4.2 mg, yield 10%.

[0137] The above reaction equation is as follows:

[0138]

[0139] 1 H NMR (400 MHz, CDC13) δ 7.96 (d, J = 8.1 Hz, 2H), 7.26 (d, J = 8.1 Hz, 2H), 4.36 (q, J = 7.2 Hz, 2H), 3.71 - 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 = 7.2 Hz, 3H); 13 C NMR (101 MHz, CDC13) δ 166.7, 147.3, 129.7, 128.4, 128.2, 62.0, 60.8, 33.8, 32.1, 14.3.

[0140] The above described embodiments are only preferred embodiments of the present application, merely used to explain the present application, and are not intended to limit the scope of the present application. For those skilled in the art, of course, other embodiments can be easily made by substitution or change according to the technical content disclosed in the present specification, and therefore, any changes and improvements made on the principles of the present application shall be included in the scope of the present application.

Claims

1. A method for synthesizing 3-substituted propanol compounds using allyl alcohols as substrates, characterized in that, Includes the following steps: Using allyl alcohol and pinacol diborate ester as substrates, and a monovalent copper salt as a catalyst, the alkyl borate esters shown in Formula II were reacted in an organic solvent under the action of a base, a proton source, and a ligand according to the following reaction formula. Tetrahydrofuran, 30% H2O2, and 1 mol / L NaOH were added to the alkyl borate esters shown in Formula II, and the oxidation reaction was carried out by stirring at room temperature to obtain 3-substituted propanols shown in Formula III. ， The allyl alcohol represented by Formula I is specifically: , , , , , The 3-substituted propanol compounds obtained according to formula III are specifically as follows: , , , , , The alkali is sodium trimethylsiloxy; The ligand is 4,5-bis(diphenylphosphino)-9,9-dimethyloxanthracene; the proton source is selected from tert-butanol, methanol and ethanol, and the molar amount of the proton source is 2 to 3 times the molar amount of allyl alcohol shown in Formula I.

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

3. 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.

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

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

6. The method according to claim 1, characterized in that, The molar ratio of allyl alcohol and pinacol diboronic acid ester shown in Formula I is 1:2~4.

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