Direct reduction method of alkyl alcohol or aldehyde ketone substrate

Abstract

The invention provides a direct reduction method of an alkyl alcohol or aldehyde ketone substrate, and belongs to the technical field of organic compound reduction. In an organic solvent, in the presence of an activator, thiophenol or thioether, a catalyst and a molecular sieve, an alcohol substrate is subjected to a dehydroxylation reduction reaction, or an aldehyde ketone substrate is subjected to methylene reduction, and a reduction product can be prepared. According to the present invention, the direct reduction of the alkyl alcohol or aldehyde ketone substrate can be achieved, the good substrate universality and functional group compatibility are provided, the yield is high, the purity is good, the production cost is low, the method is suitable for industrial production, and the excellent reaction result can be provided by most of the substrates.

Description

Technical Field

[0001] The present application relates to a direct reduction method of an alkyl alcohol or aldehyde ketone substrate, and belongs to the technical field of organic compound reduction. Background Art

[0002] Hydroxyl (-OH) is a very common functional group, which often plays a bridging role in the transformation process of organic synthesis. In the process of compound synthesis, some groups are usually introduced first due to the reasons of synthetic selection to reduce the difficulty of synthesizing compounds and improve their yield. However, sometimes in organic synthetic chemistry, it is necessary to directly remove the hydroxyl group at a certain position to obtain the desired intermediate or target product. At this time, it is necessary to remove the hydroxyl group with the help of a suitable chemical method. Therefore, the method of selectively eliminating common hydroxyl functional groups from molecules has attracted widespread attention from chemists. Such methods have also been widely used in the late modification of complex substrates. In previous studies, alcohol deoxygenation can be completed through the corresponding xanthate intermediate in the Barton-McCombie reaction (see formula 1). Unfortunately, the current Barton-McCombie reaction dehydroxylation reaction relies on stoichiometric trialkyltin hydrogen and thiocarbonyl activation functional groups, and the reaction reagents are highly toxic. Therefore, the development of an alternative deoxygenation method remains a considerable challenge.

[0003]

[0004] In recent years, prefunctionalization of alcohols to carboxylates, such as oxalates, toluates, and benzoates, has attracted attention as a strategy for deoxygenative transformations in a radical environment. Similarly, the in situ formation of reactive alcohol derivatives using N-heterocyclic carbenes (NHCs) and phosphines is an effective strategy for cleaving carbon-oxygen bonds. For example, Doyle and Rovis reported the photoredox-catalyzed deoxygenation of benzyl alcohol by in situ generated phosphite radicals. Wickens described a practical protocol for the removal of alcohol functional groups by reductive cleavage of their benzoate analogs. Schuppe described a protocol for the hydrogenation defunctionalization of alcohols via isonitrile intermediates. Although stoichiometric derivatization of hydroxyl groups leads to selective schemes for various transformations, the strategy is not ideal when considering atom and step economy. To address this issue, catalytic strategies for deoxygenative transformations of non-derivatized alcohols are an area of ​​considerable synthetic interest. However, it has proven challenging to develop direct deoxygenation reactions of non-activated alkyl alcohols. Summary of the invention

[0005] In view of this, the first object of the present application is to provide a method for direct dehydroxylation reduction of alkyl alcohols to achieve direct dehydroxylation reduction of alkyl alcohols.

[0006] Specifically, the present application is implemented through the following scheme:

[0007] A direct dehydroxylation reduction method of an alkyl alcohol. In an organic solvent, in the presence of an activator, benzenethiol or thioether, a catalyst and a molecular sieve, the alcohol substrate shown in formula (II) is subjected to a dehydroxylation reduction reaction, and the reduction product shown in formula (I) can be prepared;

[0008] The activator is a tetraaryl borate;

[0009] The reaction formula corresponding to the above reduction method is expressed as:

[0010] R is H, alkyl or carbocyclic.

[0011] The above scheme introduces a new photocatalytic reaction system, which can oxidize sodium tetraphenylborate to generate a neutral boron radical. The neutral boron radical directly activates ordinary alkyl alcohols to remove alcohol hydroxyl groups, promoting the direct homolytic conversion of alcohol hydroxyl groups. It can not only rapidly activate alcohol hydroxyl groups to generate radicals, thus avoiding many other side reactions of alcohol hydroxyl groups; its deoxygenation process does not require pre-activation of alcohols, and has good reaction results for most alcohol substrates.

[0012] Furthermore, as a preference:

[0013] The alkyl includes unsubstituted C 1 ~C 30 alkyl or substituted C 1 ~C 30 alkyl. More preferably, the substituent corresponding to the substitution is C 6 -C 10 aryl, OH, OBz, COOEt, CF 3 , OMe, OPh, OTBS, halogen, or any one of CN.

[0014] The carbocyclic ring is a 6-20 membered carbocyclic ring formed by carbon-carbon bonds.

[0015] The activator is sodium tetraphenylborate (NaBPh 4 ), lithium tetraphenylborate (LiBPh 4 ) or potassium tetraphenylborate (KBPh 4 ).

[0016] The catalyst is triphenylamine (Ph 3 N) or diphenylamine (Ph 2 NH)

[0017] The benzenethiol is ρ-Br-C 6 H 4 -SH, ρ-Cl-C 6 H 4 -SH, ρ-F-C6 H 4 -SH, ρ-CF 3 -C 6 H 4 Any one of -SH.

[0018] The organic solvent is any one of solvents such as dichloromethane (DCM) and dichloroethane (DCE).

[0019] The molecular sieve is an MS-type molecular sieve.

[0020] The molar concentration of the alcohol substrate in the organic solvent is 0.05 - 1.0 mol / L.

[0021] The alcohol substrate is

[0022]

[0023] 8 - 12-membered carbocyclic alcohol.

[0024] The reaction temperature of the dehydroxylation reduction reaction is 30 - 60 °C, and the reaction time is 10 - 48 h. More preferably, the light wavelength in the reaction.

[0025] The reductive deoxygenation of ketones to the corresponding saturated compounds has received great interest due to its extensive development in the conversion of biomass raw materials and petrochemicals. In particular, this process is of great significance in the synthesis of various structural units in drugs. In this regard, the Clemensen reduction and the Wolff-Kishner-Huang reaction are classical and powerful synthetic methods. Unfortunately, both methods use stoichiometric amounts of toxic reagents and require strict reaction conditions.

[0026] Therefore, the second object of the applicant is to provide a method for the methylene reduction of aldehyde-ketone substrates, which can also achieve efficient deoxygenation reduction of carbonyl compounds such as aldehyde-ketones under mild conditions.

[0027] A direct methylene reduction method of an aldehyde-ketone substrate. In an organic solvent, in the presence of an activator, benzenethiol or thioether, a catalyst and a molecular sieve, the aldehyde-ketone substrate is subjected to a methylene reduction reaction to obtain a reduction product;

[0028] The activator is a tetraaryl borate;

[0029] The molar concentration of the aldehyde-ketone substrate in the organic solvent is 0.05 - 1.0 mol / L;

[0030] The reaction temperature of the methylene reduction reaction is 30 - 60 °C, and the reaction time is 10 - 48 h;

[0031] The corresponding reaction formula for the methylene reduction is expressed as follows:

[0032] R is H, alkyl or carbocyclic ring.

[0033] Preferably:

[0034] The structural formula of the aldehyde-ketone substrate is a chain aldehyde, a chain ketone, a 6- to 20-membered carbocyclic aldehyde, a 6- to 20-membered carbocyclic ketone,

[0035]

[0036] For alkyl, carbocyclic ring, activator, catalyst, benzenethiol, organic solvent and molecular sieve, the selection of the above alkyl alcohol can be referred to.

[0037] The beneficial effects of the present invention are as follows:

[0038] (1) In the present invention, the dehydroxylation reaction is carried out with alcohol as the substrate, and the methylene reduction reaction is carried out with aldehyde and copper as the substrates. Without pretreatment to prepare intermediate products, the reduction products can be directly obtained.

[0039] (2) The above reduction reaction has good substrate generality and functional group compatibility, with high yield, good purity, low production cost, more suitable for industrial production, and excellent reaction results can be obtained for most substrates.

[0040] (3) The dehydroxylation reaction of alcohol and the methylene reduction reaction of aldehyde-copper have very important uses in synthesis and medicinal chemistry. The synthetic method developed by us is not only simple and efficient, but also very practical.

[0041] The above direct reduction method developed in this application is an efficient deoxygenation scheme. The reaction is carried out under mild conditions, and all the reagents used in the reaction are commercially available and inexpensive. The substrate alcohol does not need to be pre-activated, and the reaction is completed in one step. It is the first example of a radical deoxygenation reaction of non-activated alkyl alcohol. In addition, this deoxygenation scheme can also be applied to substrates such as aldehyde-ketone, overcoming the huge problems in traditional synthesis. We expect that this deoxygenation scheme will become a useful strategic tool in synthetic chemistry, providing interesting opportunities for the development of rich deoxygenation reactions in sustainable synthesis. Detailed implementation manners

[0042] In order to make the technical problems, technical solutions and beneficial effects to be solved by this application clearer, the technical solutions of this application will be further described in detail below in combination with specific cases in the embodiments of this application. It should be understood that the specific embodiments described herein are only used to explain this application and are not used to limit the technical solutions of this application. Based on the embodiments in this application, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the scope of protection of this application.

[0043] Example 1

[0044] In this example, the direct dehydroxylation reduction of alkyl alcohol was carried out as follows:

[0045] A magnetic stir bar, alcohol substrate (0.2 mmol, 1 equiv), NaBPh 4 (1.2 mmol, 6 equiv), benzenethiol (0.1 mmol, 50 mol%), Ph 3 N (0.1 mmol, 50 mol%), and molecular sieve (30 mg) were added into a dried sealed tube. The nitrogen atmosphere was replaced three times, and anhydrous DCE (2 mL) was added. The sealed tube was closed and reacted under 400 nm light irradiation for 24 hours. It was extracted three times with DCM, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure. The target product was obtained by silica gel column chromatography as a colorless liquid compound with a yield of 78%.

[0046] The reaction formula is expressed as follows:

[0047]

[0048] Butylbenzene(2). 1 1H NMR (400 MHz, Chloroform-d) δ 7.37 (q, J = 6.5, 5.4 Hz, 2H), 7.29 (d, J = 7.4 Hz,

[0049] 3H), 2.72 (t, J = 7.8 Hz, 2H), 1.71 (p, J = 7.6 Hz, 2H), 1.47 (h, J = 7.3 Hz, 2H), 1.04 (t, J = 7.3 Hz, 3H). 13 13C NMR (101 MHz, CDCl 3 ) δ 142.90, 128.39, 128.19, 125.52, 35.66, 33.67, 22.37, 13.95.

[0050] Example 1-1

[0051] This example was the same as that of Example 1, except that: NaBPh 4 was replaced with LiBPh 4 and KBPh 4 in turn, and the yields were 71% and 69% respectively.

[0052] Example 1-2

[0053] This example was the same as that of Example 1, except that: ρ-Br-C 6 H 4-SH was replaced by ρ-Cl-C 6 H 4 -SH, ρ-CF 3 -C 6 H 4 -SH, ρ-F-C 6 H 4 -SH, and the yields were 70%, 63%, and 69% in sequence.

[0054] Examples 1 - 3

[0055] This example was set the same as Example 1, except that: Ph 3 N was replaced by Ph 2 NH, and the yield was 53%.

[0056] Examples 1 - 4

[0057] This example was set the same as Example 1, except that: DCE was replaced by DCM, and the yield was 61%.

[0058] The above cases prove that the reduction system provided in this case has good universality.

[0059] Example 2

[0060] This example was set the same as Example 1, except that: the structure of the alkyl alcohol was different, and a colorless liquid compound was obtained with a yield of 71%.

[0061] The alkyl alcohol and the corresponding reduced product structures are as follows (reaction conditions are omitted):

[0062]

[0063] Phenylpentane(3). 1 H NMR(400MHz,Chloroform-d)δ7.31 - 7.25(m,2H),7.18(d,J=

[0064] 7.3Hz,3H),2.65 - 2.54(m,2H),1.62(p,J=7.4Hz,2H),1.33(dp,J=9.1,5.3Hz,4H),0.89(t,J=6.8Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ142.95,128.39,128.20,125.52,35.95,31.52,31.20,22.54,14.03.

[0065] Example 3

[0066] This example has the same settings as Example 1, except that: the structure of the alkyl alcohol is different, and a colorless liquid compound is obtained with a yield of 60%.

[0067] The structures of the alkyl alcohol and the corresponding reduction product are as follows (reaction conditions are omitted):

[0068]

[0069] 4-butylbenzoic acid methyl ester(4). 1 H NMR(400MHz,Chloroform-d)δ7.95(d,J=8.3Hz,2H),7.24(d,J=8.2Hz,2H),3.89(s,3H),2.65(t,2H),1.66-1.56(m,2H),1.41-1.30(m,2H),0.93(t,J=7.3Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ167.13,148.41,129.56,128.37,127.56,,51.87,35.65,33.22,22.26,13.84.

[0070] Example 4

[0071] This example has the same settings as Example 1, except that: the structure of the alkyl alcohol is different, and a colorless liquid compound is obtained with a yield of 60%.

[0072] The structures of the alkyl alcohol and the corresponding reduction product are as follows (reaction conditions are omitted):

[0073]

[0074] Benzylbutyl ether(5). 1 H NMR(400MHz,Chloroform-d)δ7.37-7.26(m,5H),4.51(s,2H),3.48(t,J=6.6Hz,2H),1.64-1.58(m,2H),1.44-1.36(m,2H),0.92(t,J=7.4Hz,3H). 13 CNMR(101MHz,CDCl 3 )δ138.70,128.32,127.60,127.44,72.84,70.21,31.84,19.37,13.93.

[0075] Example 5

[0076] This example has the same settings as Example 1, except that: the structure of the alkyl alcohol is different, resulting in a colorless liquid compound with a yield of 90%.

[0077] The structures of the alkyl alcohol and the corresponding reduction product are as follows (reaction conditions are omitted):

[0078]

[0079] (p)-chloropropylbenzene(6). 1 H NMR(400MHz,Chloroform-d)δ7.23(d,J=8.4Hz,2H),7.10(d,J=8.3Hz,2H),2.55(t,2H),1.67-1.56(m,2H),0.92(t,J=7.3Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ141.04,131.25,129.77,128.26,37.33,24.46,13.68.

[0080] Example 6

[0081] This example has the same settings as Example 1, except that: the structure of the alkyl alcohol is different, resulting in a colorless liquid compound with a yield of 62%.

[0082] The structures of the alkyl alcohol and the corresponding reduction product are as follows (reaction conditions are omitted):

[0083]

[0084] 1-chlorohexane(7). 1 H NMR(400MHz,Chloroform-d)δ3.53(t,J=6.8Hz,2H),1.77(p,J=6.9Hz,2H),1.42(q,J=7.1Hz,2H),1.30(tq,J=7.3,4.4,3.1Hz,4H),0.89(t,J=6.7Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ45.19,32.60,31.06,26.55,22.49,13.97.

[0085] Example 7

[0086] This example has the same settings as Example 1, except that: the structure of the alkyl alcohol is different, resulting in a colorless liquid compound with a yield of 65%.

[0087] The structures of the alkyl alcohols and their corresponding reduction products are as follows (reaction conditions are omitted):

[0088]

[0089] 1-bromohexane(8). 1 H NMR(400MHz,Chloroform-d)δ3.41(t,J=6.9Hz,2H),1.85(p,J=7.0Hz,2H),1.43(p,J=7.2Hz,2H),1.30(qt,J=7.4,4.6Hz,4H),0.90(t,J=6.7Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ34.08,32.79,30.94,27.85,22.47,13.98.

[0090] Example 8

[0091] This example is the same as that of Example 1, except that: the structure of the alkyl alcohol is different, and a colorless liquid compound is obtained with a yield of 81%.

[0092] The structures of the alkyl alcohols and their corresponding reduction products are as follows (reaction conditions are omitted):

[0093]

[0094] 1,1-diphenylpropane(9). 1 H NMR(400MHz,Chloroform-d)δ7.30-7.15(m,10H),3.80(t,J=7.8Hz,1H),2.08(p,J=7.4Hz,2H),0.91(t,J=7.3Hz,3H). 13 C NMR(101MHz,CDCl 3 )δ145.14,128.33,127.89,125.98,53.22,28.56,12.78.

[0095] Example 9

[0096] This example is the same as that of Example 1, except that: the structure of the alkyl alcohol is different, and a colorless liquid compound is obtained with a yield of 72%.

[0097] The structures of the alkyl alcohols and their corresponding reduction products are as follows (reaction conditions are omitted):

[0098]

[0099] Butylbenzene(10). 1 1H NMR(400MHz,Chloroform-d)δ7.37(q,J=6.5,5.4Hz,2H),7.29

[0100] (d,J=7.4Hz,3H),2.72(t,J=7.8Hz,2H),1.71(p,J=7.6Hz,2H),1.47(h,J=7.3Hz,2H),1.04(t,J=7.3Hz,3H). 13 13C NMR(101MHz,CDCl 3 )δ142.90,128.39,128.19,125.52,35.66,33.67,22.37,13.95.

[0101] Example 10

[0102] This example is set the same as Example 1, except that: the structure of the alkyl alcohol is different, and a colorless liquid compound is obtained with a yield of 70%.

[0103] The structures of the alkyl alcohol and the corresponding reduction product are as follows (reaction conditions are omitted):

[0104]

[0105] Cyclooctane(11). 1 1H NMR(400MHz,Chloroform-d)δ1.53(s,16H). 13 13C NMR(101MHz,CDCl 3 )δ26.66.

[0106] Example 11

[0107] This example is set the same as Example 1, except that: the structure of the alkyl alcohol is different, and a colorless liquid compound is obtained with a yield of 71%.

[0108] The structures of the alkyl alcohol and the corresponding reduction product are as follows (reaction conditions are omitted):

[0109]

[0110] Cyclododecane(12). 1 1H NMR(400MHz,Chloroform-d)δ1.33(s,24H). 13 13C NMR(101MHz,CDCl 3 )δ23.63.

[0111] Example 12

[0112] This example is the same as that of Example 1, except that: the structure of the alkyl alcohol is different, and a colorless liquid compound is obtained with a yield of 65%.

[0113] The structures of the alkyl alcohol and the corresponding reduction product are as follows (reaction conditions are omitted):

[0114]

[0115] Isopentenyl benzene(13). 1 H NMR(400MHz,Chloroform-d)δ7.33 - 7.25(m,2H),7.22 - 7.16(m,3H),2.67 - 2.58(m,2H),1.65 - 1.49(m,3H),0.95(d,J=6.5Hz,6H). 13 C NMR(101MHz,CDCl 3 )δ143.10,128.33,128.23,125.50,40.85,33.78,27.67,22.53.

[0116] Example 13

[0117] This example is the same as that of Example 1, except that: the structure of the alkyl alcohol is different, and a colorless liquid compound is obtained with a yield of 68%.

[0118] The structures of the alkyl alcohol and the corresponding reduction product are as follows (reaction conditions are omitted):

[0119]

[0120] 1-ethyl-4-methoxybenzene(14). 1 H NMR(400MHz,Chloroform-d)δ7.13(d,J=8.5Hz,2H),6.84(d,J=8.6Hz,2H),3.80(s,3H),2.60(q,J=7.6Hz,2H),1.22(t,J=7.6Hz,3H). 13 CNMR(101MHz,CDCl 3 )δ157.58,136.38,128.68,113.70,55.25,27.95,15.89.

[0121] Example 14

[0122] This example has the same settings as Example 1, except that: the structure of the alkyl alcohol is different, and a colorless liquid compound is obtained with a yield of 68%.

[0123] The structures of the alkyl alcohol and the corresponding reduction product are as follows (reaction conditions are omitted):

[0124]

[0125] 1,2,3,4-Tetrahydronaphthalene(15). 1 H NMR(400MHz,Chloroform-d)δ7.16-7.02(m,4H),2.82-2.76(m,4H),1.85-1.78(m,4H). 13 C NMR(101MHz,CDCl 3 )δ137.10,129.10,125.37,29.36,23.19.

[0126] Example 15

[0127] This example has the same settings as Example 1, except that: the structure of the alkyl alcohol is different, and a colorless liquid compound is obtained with a yield of 66%.

[0128] The structures of the alkyl alcohol and the corresponding reduction product are as follows (reaction conditions are omitted):

[0129]

[0130] Indan(16). 1 H NMR(400MHz,Chloroform-d)δ7.28-7.17(m,2H),7.17-7.08(m,2H),2.91(t,J=7.5Hz,4H),2.06(p,J=7.4Hz,2H). 13 C NMR(101MHz,CDCl 3 )δ144.13,125.94,124.34,32.84,25.32.

[0131] Example 16

[0132] This example has the same settings as Example 1, except that: the structure of the alkyl alcohol is different, and a colorless liquid compound is obtained with a yield of 73%.

[0133] The structures of the alkyl alcohol and the corresponding reduction product are as follows (reaction conditions are omitted):

[0134]

[0135] 1-isobutyl-4-isopropylbenzene(17). 1 H NMR(400MHz,Chloroform-d)δ7.14(d,J=7.9Hz,2H),7.07(d,J=7.8Hz,2H),2.96-2.81(m,1H),2.45(d,J=7.2Hz,2H),1.89-1.81(m,1H),1.25(d,J=7.0Hz,6H),0.91(d,J=6.6Hz,6H). 13 C NMR(101MHz,CDCl 3 )δ146.04,138.97,128.98,126.05,45.03,33.65,30.23,24.07,22.42.

[0136] Example 17

[0137] This example has the same setup as Example 1, except that: the structure of the alkyl alcohol is different, obtaining a colorless liquid compound with a yield of 54%.

[0138] The structures of the alkyl alcohol and the corresponding reduction product are as follows (reaction conditions are omitted):

[0139]

[0140] (22E)-Stigmasta-5,22-diene(18). 1 H NMR(400MHz,Chloroform-d)δ5.27(dt,J=4.9,2.0Hz,1H),5.15(dd,J=15.1,8.6Hz,1H),5.01(dd,J=15.2,8.6Hz,1H),2.52-2.13(m,2H),2.04(ddd,J=9.5,5.8,2.7Hz,1H),2.00(d,J=4.2Hz,1H),1.99-1.87(m,3H),1.85-1.80(m,1H),1.77-1.60(m,5H),1.43(dd,J=6.8,2.9Hz,2H),1.42-1.28(m,6H),1.22-1.16(m,4H),1.09-1.04(m,2H),1.00(s,3H),0.85(t,J=5.6Hz,6H),0.82(d,J=4.2Hz,3H),0.80(s,3H),0.79(s,3H). 1313C NMR (101 MHz, Chloroform-d) δ 143.73, 138.39, 129.19, 118.96, 56.97, 55.96, 51.23, 50.61, 42.19, 40.52, 39.88, 39.75, 37.54, 32.90, 31.88, 29.70, 28.94, 28.07, 25.41, 24.35, 22.57, 21.22, 21.09, 20.75, 19.48, 18.97, 12.25, 12.05. HRMS (ESI + ) Calc: [M+H] + for C 29 H 48 + = 397.3829, measured 397.3808.

[0141] The above method can be applied to the late-stage modification of natural products and drug molecules without pre-functionalization reactions. The reaction is simple and has good functional group compatibility. The alkyl alcohol is stigmasterol, which belongs to a natural plant sterol. Natural plant sterols are structurally similar to animal sterols such as cholesterol and are an active ingredient in plants. They are present in various vegetable oils and are widely used in industries such as medicine, food, and cosmetics. The directly reduced deoxygenated product can be used for the analysis and identification of drug impurities.

[0142] Example 18

[0143] This example is the same as the setup in Example 1, except that: the structure of the alkyl alcohol is different, and a colorless liquid compound is obtained with a yield of 60%.

[0144] The structures of the alkyl alcohol and the corresponding reduction product are as follows (reaction conditions are omitted):

[0145]

[0146] tert-butyl(((5R,8R,9S,10S,13S,14S)-3-butyl-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)oxy)dimethylsilane (19). 11H NMR (400 MHz, Chloroform-d) δ 3.58 - 3.49 (m, 1H), 1.85 (dtd, J=13.2, 9.2, 5.8 Hz, 1H), 1.75 - 1.62 (m, 3H), 1.53 (dddd, J=15.9, 9.3, 7.2, 3.7 Hz, 3H), 1.47 - 1.33 (m, 3H), 1.31 - 1.13 (m, 13H), 1.11 - 0.89 (m, 6H), 0.88 (s, 9H), 0.85 (d, J=4.9 Hz, 3H), 0.79 (s, 1H), 0.75 (s, 2H), 0.68 (s, 3H), 0.00 (d, J=3.1 Hz, 6H). 13 13C NMR (101 MHz, Chloroform-d) δ 81.91, 55.03, 50.81, 46.81, 43.32, 38.77, 38.04, 37.30, 37.19, 36.25, 35.85, 35.66, 31.84, 30.95, 29.21, 29.03, 28.99, 25.88, 23.55, 23.04, 20.66, 18.12, 14.18, 12.37, 11.41, -4.49, -4.80. HRMS (ESI + ) Calc: [M + H] + for C 29 H 54 OSi + =447.4017, measured 447.4034.

[0147] Example 19

[0148] In this example, the methylene reduction of the aldehyde - ketone substrate was carried out as follows:

[0149] A magnetic stir bar, the aldehyde - ketone substrate (0.2 mmol, 1 equiv), NaBPh 4 (1.2 mmol, 6 equiv), benzenethiol (0.1 mmol, 50 mol%), Ph 3 N (0.1 mmol, 50 mol%), and molecular sieve (30 mg) were added to a dried sealed tube. The nitrogen atmosphere was replaced three times, and anhydrous DCE (2 mL) was added. The sealed tube was closed and reacted under 400 nm light irradiation for 24 hours. It was extracted three times with DCM, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure. The target product was obtained by silica gel column chromatography as a colorless liquid compound with a yield of 71%.

[0150] The reaction equation is expressed as follows:

[0151]

[0152] Indan(20). 1 H NMR(400MHz,Chloroform-d)δ7.28 - 7.17(m,2H),7.17 - 7.08(m,2H),2.91(t,J=7.5Hz,4H),2.06(p,J=7.4Hz,2H). 13 C NMR(101MHz,CDCl 3 )δ144.13,125.94,124.34,32.84,25.32.

[0153] Example 20

[0154] This example is the same as that of Example 19, except that: the structures of the aldehyde - ketone substrates are different, and a colorless liquid compound is obtained with a yield of 63%.

[0155] The structures of the aldehyde - ketone substrates and the corresponding reduction products are as follows (reaction conditions are omitted):

[0156]

[0157] 5 - Bromoindane(21). 1 H NMR(400MHz,Chloroform-d)δ7.36(s,1H),7.25(d,J=9.5Hz,1H),7.09(d,J=7.9Hz,1H),2.88(dt,J=18.6,7.4Hz,4H),2.08(p,J=7.4Hz,2H). 13 C NMR(101MHz,CDCl 3 )δ146.65,143.10,128.90,127.45,125.75,119.60,32.78,32.35,25.51.

[0158] Example 21

[0159] This example is the same as that of Example 19, except that: the structures of the aldehyde - ketone substrates are different, and a colorless liquid compound is obtained with a yield of 72%.

[0160] The structures of the aldehyde - ketone substrates and the corresponding reduction products are as follows (reaction conditions are omitted):

[0161]

[0162] Cyclododecane(22). 1 H NMR(400MHz,Chloroform-d)δ1.33(s,24H). 1313C NMR (101 MHz, CDCl 3 ) δ 23.63.

[0163] Example 22

[0164] This example has the same setup as Example 19, except that: the structure of the aldehyde-ketone substrate is different, and a colorless liquid compound is obtained with a yield of 74%.

[0165] The structures of the aldehyde-ketone substrate and the corresponding reduction product are as follows (reaction conditions are omitted):

[0166]

[0167] Adamantane(23). 1 1H NMR (400 MHz, Chloroform-d) δ 1.90 - 1.84 (m, 4H), 1.76 (s, 12H). 13 13C NMR (101 MHz, Chloroform-d) δ 37.73, 28.32.

[0168] Example 23

[0169] This example has the same setup as Example 19, except that: the structure of the aldehyde-ketone substrate is different, and a colorless liquid compound is obtained with a yield of 56%.

[0170] The structures of the aldehyde-ketone substrate and the corresponding reduction product are as follows (reaction conditions are omitted):

[0171]

[0172] Phenylpentane(24). 1 1H NMR (400 MHz, Chloroform-d) δ 7.29 (t, J = 7.5 Hz, 2H), 7.20 (d, J

[0173] = 7.4 Hz, 3H), 2.63 (t, J = 7.8 Hz, 2H), 1.62 (p, J = 7.6 Hz, 2H), 1.38 (q, J = 7.4 Hz, 2H), 0.95 (t, J = 7.3 Hz, 3H). 13 13C NMR (101 MHz, Chloroform-d) δ 142.90, 128.39, 128.19, 125.52, 35.66, 33.67, 22.37, 13.95.

[0174] Example 24

[0175] This example has the same settings as Example 19, except that: the structures of the aldehyde-ketone substrates are different, and a colorless liquid compound is obtained with a yield of 70%.

[0176] The structures of the aldehyde-ketone substrates and the corresponding reduction products are as follows (reaction conditions are omitted):

[0177]

[0178] 5-(2-Methylpropyl)-1,3-benzodioxole(25). 1 H NMR(400MHz,Chloroform-d)δ6.72(d,J=7.9Hz,1H),6.67-6.55(m,2H),5.92(s,2H),2.39(d,J=7.2Hz,2H),1.80(dt,J=13.5,6.8Hz,1H),0.89(d,J=6.6Hz,6H). 13 C NMR(101MHz,Chloroform-d)δ147.31,145.40,135.57,121.81,109.42,107.86,100.65,45.13,30.37,22.26.

[0179] The above-described embodiments only represent several feasible implementation manners of the present invention. The description is relatively specific and detailed, but it should not be construed as a limitation on the scope of the patent of the present invention. The embodiments are not intended to limit the scope of protection in the claims of the present invention. For those of ordinary skill in the art, without departing from the concept of the present invention, several modifications and improvements can still be made. Any equivalent implementation or change made without departing from the present invention should be included in the technology of the present invention.

Claims

1. A direct dehydroxylation reduction method for an alkyl alcohol, characterized in that: In an organic solvent, in the presence of an activator, thiophenol or thioether, a catalyst and a molecular sieve, the alcohol substrate represented by formula (II) is subjected to a dehydroxylation reduction reaction to prepare a reduction product represented by formula (I); The activator tetraaryl borate; The molar concentration of the alcohol substrate in the organic solvent is 0.05 to 1.0 mol / L; The reaction temperature of the dehydroxylation reduction reaction is 30 to 60°C, and the reaction time is 10 to 48 hours; The reaction formula corresponding to the above dehydroxylation reduction is expressed as: R is H, alkyl or carbocyclic ring.

2. The direct dehydroxylation reduction method of an alkyl alcohol according to claim 1, characterized in that: The alkyl group includes unsubstituted C1 to C 30 Alkyl or substituted C1~C 30 The carbocyclic ring is a 6- to 20-membered carbon ring connected by carbon-carbon bonds.

3. The direct dehydroxylation reduction method of an alkyl alcohol according to claim 1, characterized in that: The substitution corresponding to the substitution is C6-C 10 Aryl, OH, OBz, COOEt, CF3, OMe, OPh, OTBS, halogen, or any one of CN.

4. The direct dehydroxylation reduction method of an alkyl alcohol according to claim 1, characterized in that: The activator is sodium tetraphenylborate, lithium tetraphenylborate or potassium tetraphenylborate.

5. The direct dehydroxylation reduction method of an alkyl alcohol according to claim 1, characterized in that: The catalyst is triphenylamine or diphenylamine.

6. The direct dehydroxylation reduction method of an alkyl alcohol according to claim 1, characterized in that: The thiophenol is any one of ρ-Br-C6H4-SH, ρ-Cl-C6H4-SH, ρ-F-C6H4-SH, and ρ-CF3-C6H4-SH.

7. The direct dehydroxylation reduction method of an alkyl alcohol according to claim 1, characterized in that: The molecular sieve is an MS type molecular sieve.

8. The direct dehydroxylation reduction method of an alkyl alcohol according to claim 1, characterized in that: The alcohol substrate is 8-12 membered carbocyclic alcohol.

9. A method for direct methylene reduction of aldehyde and ketone substrates, characterized in that: In an organic solvent, in the presence of an activator, thiophenol or thioether, a catalyst and a molecular sieve, the aldehyde or ketone substrate is subjected to a methylene reduction reaction to obtain a reduction product; The activator tetraaryl borate; The molar concentration of the aldehyde and ketone substrate in the organic solvent is 0.05 to 1.0 mol / L; The reaction temperature of the methylene reduction reaction is 30-60°C and the reaction time is 10-48h; The reaction formula corresponding to the above methylene reduction is expressed as: R is H, alkyl or carbocyclic ring.

10. The method for direct methylene reduction of an aldehyde or ketone substrate according to claim 9, characterized in that: The structural formula of the aldehyde and ketone substrate is chain aldehyde, chain ketone, 6-20-membered carbon ring aldehyde, 6-20-membered carbon ring ketone,

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