Method for synthesizing silicon-based substituted homoallylic alcohol compound through chromium / visible light concerted catalysis

Abstract

The invention relates to the technical field of organic synthesis, in particular to a method for preparing a silicon-based substituted homoallylic alcohol compound through a three-component reaction of alpha-silicon-based substituted conjugated diene, an aldehyde compound and a Hantzsch ester compound under the synergistic catalysis of a chromium catalyst and a photocatalyst. The method comprises the following steps: in a nitrogen atmosphere, adding alpha-silicon-based substituted conjugated diene, an aldehyde compound, a Hantzsch ester compound, a photocatalyst and a chromium catalyst into an organic solvent, stirring the mixture at 25 DEG C under the irradiation of a 5W blue light LED lamp until the reaction is complete, and concentrating and purifying by column chromatography to obtain the silicon-based substituted homoallylic alcohol compound. The method is mild in reaction condition, simple and convenient to operate, wide in substrate application range, good in functional group compatibility and excellent in regioselectivity and diastereoselectivity (both greater than 20: 1).

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, specifically to a method for preparing silicon-substituted high-allyl alcohol compounds by a three-component reaction of α-silicone-substituted conjugated dienes, aldehydes, and Hantzsch esters under synergistic catalysis of chromium and photo-redox. Background Technology

[0002] High-allyl alcohols are a common class of organic structural units that play an important role in organic synthesis. Traditionally, these structures are prepared via the addition reaction of an allyl metal reagent to a carbonyl group (aldehyde, ketone). However, the structurally complex allyl halide precursors are often difficult to prepare, and regioselectivity is hard to control. In recent years, transition metal-mediated addition to the carbonyl group via an allyl radical intermediate has emerged as a new option, effectively solving the problem of difficult precursor preparation. However, the regioselective functionalization of allyl radicals presents a new challenge. Common methods often rely on introducing coordination directing groups to control the metallization site through steric and coordination synergy (Reference 1: J.Am.Chem.Soc.2018, 140, 12705-12709; Reference 2: ACS Catal.2020, 10, 1621-1627; Reference 3: ACS Catal.2020, 10, 11841-11847; Reference 4: Chem 2024, 10, 998-1014). However, the presence of coordination directing groups limits the applicability of substrates to some extent. Therefore, it is still necessary to develop other general and efficient strategies to achieve highly regioselective construction of this structure.

[0003]

[0004] Due to its inherent electronic properties, silicon can exert a stabilizing effect on the carbon-metal bond at the α-position. This invention mainly studies the regioselectivity of the reaction between alkyl radicals and alkyl-substituted diene radicals, which produce an allyl chromium intermediate, and aldehydes, thereby achieving modular and efficient preparation of high-allyl alcohol compounds containing alkenyl silicon structures. Summary of the Invention

[0005] The purpose of this invention is to provide a method for preparing silicon-based substituted high-allyl alcohol compounds that is mild, easy to operate, and has excellent regio and diastereoselectivity, in order to solve the difficulties of existing methods, such as the difficulty and limitation of raw material preparation and poor regioselectivity.

[0006] The method adopted by this invention to achieve its objective includes the following steps: Under a nitrogen atmosphere, α-silyl-substituted conjugated dienes, aldehydes, Hantzsch esters, photocatalysts, and chromium catalysts are added to a reaction solvent, and the mixture is stirred until the reaction is complete under a suitable temperature and blue LED irradiation. After the reaction is complete, the mixture is concentrated and purified by column chromatography to obtain silyl-substituted high-allyl alcohol compounds.

[0007] The reaction formula of the method of the present invention can be expressed as follows:

[0008]

[0009] Formula 1 represents silicon-substituted conjugated diene compounds, Formula 2 represents aldehyde compounds, Formula 3 represents Hantzsch ester compounds, and Formula 4 represents silicon-substituted high-allyl alcohol compounds.

[0010] In Equations 1 and 4, R 1 It is tert-butyl, phenyl, benzyl, R 2 Hydrogen, methyl;

[0011] In Equations 2 and 4, R 3 It is 4-phenylphenyl, 3-cyanophenyl, 4-methyl ester phenyl, 4-trifluoromethylphenyl, 4-trifluoromethoxyphenyl, 4-fluorophenyl, 4-ethynylphenyl, 2,4,6-trimethylphenyl, 4-methoxyphenyl, 4-methylthiophenyl, 4-acetoxyphenyl, 4-acetaminophenyl, 2-naphthyl, 9-phenanthyl, 2-furanyl, 2-thienyl, 2-methoxy-5-pyridyl, trans-2-phenylvinyl, 2-phenylethyl, 2-methylthioethyl, isopropyl, cyclopropyl, cyclohexyl, phthalimide N-methyl, benzyloxymethyl;

[0012] In Equations 2 and 4, R 4 The derivatives are isopropyl, 3-pentyl, cyclohexyl, and N-tert-butoxycarbonyl-4-piperidinyl.

[0013] The photocatalyst is 2,4,5,6-tetracarbazolyl-1,3-benzonitrile (4CzIPN);

[0014] The chromium catalyst is CrCl2;

[0015] The reaction solvent is one of tetrahydrofuran, 1,4-dioxane, and acetonitrile, preferably tetrahydrofuran;

[0016] The molar ratio of the silicon-based substituted conjugated diene compound 1, aldehyde compound 2, Hantzsch ester compound 3, photocatalyst, and chromium catalyst is 2.5:1.0:2.5:0.01:0.1.

[0017] The reaction temperature is room temperature or 10-50℃, preferably 25℃;

[0018] The reaction time is 8-24 hours, preferably 20 hours;

[0019] The blue light wavelength is 420-470nm, preferably 456nm, and the LED power is 5-40W, preferably 5W.

[0020] The present invention has the following advantages and beneficial effects:

[0021] 1. The reaction conditions are mild (room temperature, visible light), the operation is simple, and no precious metal catalysts or toxic reagents are required.

[0022] 2. It has a wide range of substrate applications and excellent functional group compatibility, and is expected to be applied to the later functionalization of complex structures.

[0023] 3. The product has both high regioselectivity and high diastereoselectivity (>20:1), and the alkenylsilane and hydroxyl functional groups contained therein can be further derivatized to synthesize other high-value structures. Attached Figure Description

[0024] Figure 1 This is the proton spectrum of compound 4A in the embodiments of the present invention;

[0025] Figure 2 This is the carbon spectrum of compound 4A in the embodiments of the present invention;

[0026] Figure 3 This is the proton spectrum of compound 4B in the embodiments of the present invention;

[0027] Figure 4 This is the carbon spectrum of compound 4B in the embodiments of the present invention;

[0028] Figure 5 This is the proton spectrum of compound 4C in the embodiments of the present invention;

[0029] Figure 6 This is the carbon spectrum of compound 4C in the embodiments of the present invention; Detailed Implementation

[0030] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0031] Example 1:

[0032]

[0033] 10-Dimethyl-tert-butylsilyl-1,3-butadiene (0.25 mmol), 4-phenylbenzaldehyde (0.1 mmol), isopropyl-substituted Hantzsch ester (0.25 mmol), photocatalyst 4CzIPN (1 μmol, 1 mol%), and CrCl2 (10 μmol, 10 mol%) were added to a dry 10 mL reaction tube. After purging with nitrogen three times, anhydrous tetrahydrofuran (1 mL, 0.1 M) was added under a nitrogen atmosphere. The reaction mixture was placed under a 5 W blue LED lamp (wavelength 456 nm) and stirred at 25 °C for 20 h. The reaction solution was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the target product 4A with a yield of 92% and regioselectivity (rr) and diastereoselectivity (dr) both greater than 20:1.

[0034] Examples 2-25: Reactions of different aldehyde substrates

[0035] Referring to the reaction conditions of Example 1, different aromatic aldehydes, heteroaromatic aldehydes, and aliphatic aldehydes were used for the reaction, and the corresponding products were obtained in moderate to excellent yields (38-99%). Moreover, the regioselectivity and diastereoselectivity were generally excellent (rr, dr > 20:1).

[0036]

[0037]

[0038]

[0039] Examples 26-31: Reactions of different silicon-substituted conjugated dienes 1 and Hantzsch esters 3

[0040] Under the same conditions as in Example 1, the reactions of conjugated dienes with different silicon-substituted alkyl groups with phenylpropanal proceeded smoothly, with yields of 80% and 83%, respectively. The reactions were also well-compatible when using Hantzsch esters with different alkyl substitutions (such as isopentyl and cyclohexyl), with yields ranging from 34% to 87%, demonstrating the broad applicability of this catalytic system.

[0041]

[0042]

[0043] The above description is only a partial embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions or improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing a silicon-based substituted high-allyl alcohol compound, characterized in that: Under the synergistic catalysis of chromium catalyst and photocatalyst, silicon-substituted conjugated dienes, aldehydes and Hantzsch esters undergo a three-component reaction under blue light irradiation to obtain silicon-substituted high-allyl alcohol compounds. The structure of the silicon-based substituted conjugated diene is shown in Formula 1. The structure of the aldehyde compound is shown in Formula 2. The structure of the Hantzsch ester compounds is shown in Formula 3. The structure of the silicon-based substituted high-allyl alcohol compound is shown in Formula 4. In Equations 1 and 4, R 1 It is tert-butyl, phenyl, benzyl, R 2 Hydrogen, methyl; In Equations 2 and 4, R 3 It is 4-phenylphenyl, 3-cyanophenyl, 4-methyl ester phenyl, 4-trifluoromethylphenyl, 4-trifluoromethoxyphenyl, 4-fluorophenyl, 4-ethynylphenyl, 2,4,6-trimethylphenyl, 4-methoxyphenyl, 4-methylthiophenyl, 4-acetoxyphenyl, 4-acetaminophenyl, 2-naphthyl, 9-phenanthyl, 2-furanyl, 2-thienyl, 2-methoxy-5-pyridyl, trans-2-phenylvinyl, 2-phenylethyl, 2-methylthioethyl, isopropyl, cyclopropyl, cyclohexyl, phthalimide N-methyl, benzyloxymethyl; In equations 3 and 4, R 4 The derivatives are isopropyl, 3-pentyl, cyclohexyl, and N-tert-butoxycarbonyl-4-piperidinyl. The photocatalyst is 2,4,5,6-tetracarbazolyl-1,3-benzonitrile (4CzIPN); The chromium catalyst is CrCl2.

2. The method for preparing silicon-based substituted high-allyl alcohol compounds according to claim 1, characterized in that, The method includes the following steps: (1) Under a nitrogen atmosphere, α-silyl-substituted conjugated diene, aldehyde compound, Hantzsch ester compound, photocatalyst and chromium catalyst were added to the reaction solvent in sequence to obtain a mixture; The molar ratio of the silicon-based substituted conjugated diene compound, aldehyde compound, Hantzsch ester compound, photocatalyst, and chromium catalyst is 2.5:1.0:2.5:0.01:0.

1. (2) The mixture described in step (1) was stirred under a suitable temperature and irradiated with a 5W blue LED lamp until the reaction was complete. The crude product was concentrated and purified by column chromatography to obtain a silicon-substituted high-allyl alcohol compound; The mixture was stirred and reacted at 25 degrees Celsius for 20 hours, and the blue light used had a wavelength of 456 nm.

3. The method for preparing silicon-based substituted high-allyl alcohol compounds according to claim 2, characterized in that, In step (1), the reaction solvent is tetrahydrofuran.

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