A method for preparing a ketone compound by catalyzing a wacker-type oxidation reaction of an olefin using a cobalt complex catalyst

Abstract

The application discloses a method for preparing an organic ketone compound by catalyzing Wacker-type oxidation reaction of an olefin by using a cobalt complex catalyst, which comprises the following steps: taking 1,2-disubstituted olefin shown in formula I as raw material, taking normal pressure air as oxygen source, taking SPODA.Co complex as catalyst, and taking a silane compound as hydrogen source to prepare the organic ketone compound shown in formula II. Compared with the existing olefin Wacker-type oxidation reaction, the method is suitable for various types of olefins, has good activity and chemical selectivity, and the reaction system can tolerate easily oxidized sulfide groups. The cobalt catalyst with asymmetric tetradentate NNNO tetradentate ligand can be used to selectively perform Wacker-type oxidation reaction on various olefin raw materials. The conversion rate of the reaction is also good, generally reaches >99%, the chemical selectivity is also high, and the yield of the product organic ketone is generally 70%-99%.

Description

Technical Field

[0001] This method relates to a Wacker-type oxidation reaction of simple olefins catalyzed by a cobalt salicylaldehyde diamine oxazoline (SPODA) complex catalyst to prepare ketone compounds, and in particular, this method can prepare organic ketone compounds via a simple oxidation reaction. Background Technology

[0002] Ketones are widely found in drug molecules and natural products, including commercially available drugs and natural ketones with physiological and pharmacological activity. Furthermore, ketones are intermediates in organic synthesis and key synthons in some complex compounds; the Wacker-type oxidation of alkenes, due to its advantages of atom economy, simple operation, high reactivity, and environmental friendliness, is one of the most effective methods for obtaining ketones and has been widely used in the synthesis of pharmaceuticals and natural products, as well as the industrial production of pesticide molecules [a) M. Sono, MP Roach, EDCoulter, JH Dawson, Chem. Rev. 1996, 96, 2841–2888; b) B. Meunier, SPde Visser, S. Shaik, Chem. Rev. 2004, 104, 3947–3980; c) IG Denisov, TMMakris, SG Sligar, I. Schlichting, Chem. Rev. 2005, 105, 2253–2277; d) J. Müller, M. Bröring in Iron Catalysis in Organic Chemistry: Reactions andApplications (Ed.: B. Plietker), Wiley-VCH, Weinheim, 2008, chap. 2, pp. 29–72; e) S. Shaik, S. Cohen, Y. Wang, H. Chen, D. Kumar, W. Thiel, Chem. Rev.2010, 110, 949–1017; f) L. Podust, DH Sherman, Nat. Prod. Rep. 2012, 29,1251–1266; g) TL Poulos, Chem. Rev. 2014, 114, 3919–3962].

[0003] Oxygen is the most common elemental form of oxygen, accounting for approximately 21% of the atmosphere. Olefins, as inexpensive bulk chemicals, are mainly derived from petroleum cracking and natural gas conversion. Transition metal-catalyzed Wacker oxidation of alkenes can use oxygen or air as a single oxygen source, converting alkenes into high-value-added ketone compounds through oxygen atom transfer. These compounds have wide applications in various fields such as pharmaceuticals and chemicals. For example, roxithromycin and esomeprazole are anticancer drugs containing a carbonyl group [a) Ohno, K.; Mitsuyasu, T.; Tsuji, J. Tetrahedron 1972, 28, 3705–3720; b) Takacs, J.; Jiang, X. Curr. Org. Chem. 2003, 7, 369–396. c) Shi, Z.; Zhang, C.; Tang, C.; Jiao, N. Chem. Soc. Rev. 2012, 41, 3381–3430. d) Hu, M.; Wu, W.; Jiang, H. ChemSusChem 2019, 12, 2911–2935. e) Fernandes, RA; Jha, AK; Kumar, P. Catal. Sci. Technol. 2020, 10, [7448–7470]. Currently, a series of methods have been developed to convert simple alkenes into high-value organic ketone compounds via oxygen atom transfer reactions. Among them, the Wacker oxidation reaction of alkenes catalyzed by platinum group metals palladium has excellent catalytic activity and stability and has been applied on a large scale in industry [a) Catalysis without Precious Metals (Ed.: Bullock,RM), Wiley-VCH, Weinheim, 2010. b) Tzouras, NV; Stamatopoulos, IK; Papastavrou, AT; Liori, AA; Vougioukalakis, GC Coord. Chem. Rev.2017, 343, 25–138. c) Non-Noble Metal Catalysis: Molecular Approaches and Reactions (Eds.: Klein Gebbink, RJM; Moret, ME), Wiley-VCH, Weinheim,2019.].In 1894, Phillips first observed that Pd(II) salts could oxidize ethylene to acetaldehyde. Later, Smidt and his colleagues at Wacker Company discovered that, in the presence of copper salts and oxygen, using a catalytic amount of PdCl2, ethylene under acidic conditions underwent a similar transformation, which was called the "Wacker reaction" [Phillips, FCJ Am. Chem. Soc. 1894, 16, 700–703.].

[0004] Compared to platinum group metals (PGMs), abundant Earth-based metals such as iron and cobalt offer advantages including plentiful reserves, low cost, and good biocompatibility. They also possess smaller atomic radii, higher splitting energies, and stronger Lewis acids. These characteristics allow these abundant metals to participate in catalytic reactions using different catalytic modes than PGM catalysts. Analysis of their participation in organic reactions reveals that PGMs in organometallic catalysis often involve two-electron reactions, with metal complexes typically exhibiting low-spin states and good stability. In contrast, abundant Earth-based metals like iron and cobalt can undergo both two-electron-like redox processes and single-electron reactions via radicals, resulting in a richer range of reaction modes and enabling them to participate in a wider variety of reaction types and catalytic modes. This offers a new solution to problems that are difficult to address with PGM catalysts. Therefore, to a certain extent, abundant metals such as iron and cobalt can not only serve as substitutes for platinum group metals, but also bring new possibilities to the field of metal catalysis [a) Bolm, C.; Legros, J.; Le Paih, J.; Zani, L. Chem. Rev. 2004, 104, 6217–6254. b) Sarhan, AAO; Bolm, C.Chem. Soc. Rev. 2009, 38, 2730-2744. c) Zhang, L.; Mathew, S.; Hessels, J.; Reek, JNH; Yu, F. ChemSusChem 2021, 14, 234–250. d) Beller, M. Chem.Rev. 2019, 119, 2089–2089. e) Gandeepan, P.; Müller, T.; Zell, D.; Cera, G.; Warratz, S.; Ackermann, L. Chem. Rev. 2019, 119, 2192–2452.]. While some progress has been made in Wacker oxidation reactions using abundant metals such as iron, cobalt, and nickel to catalyze olefins, limitations exist, including long reaction times, the use of excessive reducing agents, and a limited substrate range [Rajeshwaran, P.; Trouvé, J.; Youssef, K.; Gramage‐Doria, R. Angew. Chem. Int. Ed. 2022, 61, e202211016.].A landmark work in the reported field was the 2017 work by Han's group, who achieved iron-catalyzed Wacker oxidation of olefins using simple metallic iron salts as catalysts. The reaction required 80 °C [Liu, B.; Jin, F.; Wang, T.; Yuan, X.; Han, W. Angew. Chem. Int. Ed. 2017, 56, 12712–12717.]. Subsequently, the research groups of Yamaguchi, Knölker, Gramage-Doria, etc., used similar systems to stabilize the high-valence central metal by introducing dominant ligands with different structures, thereby reducing the activation energy required for the reaction and making the reaction conditions more moderate. [a] Hashimoto, T.; Maruyama, T.; Ishimaru, T.; Matsugaki, M.; Shiota, K.; Yamaguchi, Y. ChemistrySelect 2021, 6, 5534–5537. b) Puls, F.; Knölker, H. Angew. Chem. Int. Ed. 2018, 57, 1222–1226. c) Puls, F.; Linke, P.; Kataeva, O.; Knölker, H. Angew. Chem. Int. Ed. 2021, 133, 14202–14209. d)Puls, F.; Seewald, F.; Grinenko, V.; Klauß, H.; Knölker, H. Chem. Eur. J.2021, 27, 16776–16787. (d) Schuh, T.; Kataeva, O.; 257–265. e) Trouvé, J.; Youssef, K.; Kasemthaveechok, S.; Gramage-Doria, R. ACS Catal. 2023, 13, 4421–4432.]. In 2023, Gramage-Doria's research group achieved Wacker oxidation of styrene-type substrates at room temperature using a cobalt porphyrin catalyst [Abuhafez, N.; Ehlers, AW; De Bruin, B.; Gramage‐Doria, R. Angew. Chem. Int. Ed. 2024,63, e202316825.].

[0005] In the above reactions, using abundant Earth-derived metals such as iron or cobalt to complex different types of dominant ligands achieved relatively good results in the Wacker oxidation of alkenes. However, some problems still exist: 1) the chemoselectivity of the reaction needs further optimization; 2) the compatibility of substrate functional groups is somewhat limited, such as the difficulty in retaining easily oxidized thioether groups [Rajeshwaran, P.; Trouvé, J.; Youssef, K.; Gramage‐Doria, R. Angew. Chem.Int. Ed. 2022, 61, e202211016.]. The efficient and highly selective synthesis of ketones also faces certain challenges: 1) the problem of controlling the chemoselectivity of the reaction, i.e., maximizing the formation of ketones from alkenes; 2) the problem of substrate applicability. Therefore, there is an urgent need to develop efficient methods to synthesize high-value-added ketones using simple alkenes and air as substrates. Summary of the Invention

[0006] This invention utilizes a catalyst formed by complexing the salicylaldehyde diamine phenyloxazoline tetradentate NNNO ligand (SPODA) disclosed in CN 119707848 A with inexpensive cobalt to catalyze the Wacker-type oxidation of simple 1,2-disubstituted alkenes. This method achieves excellent conversion and chemoselectivity, has a broad substrate range, and exhibits good functional group tolerance. Furthermore, by adjusting the steric hindrance of the catalyst, highly chemically viable organic ketone compounds can be obtained. This methodology can also be used to oxidize small-molecule olefins from petroleum cracking products into high-value-added ketone compounds.

[0007] This invention is achieved through the following technical solution:

[0008] A method for preparing organic ketone compounds by Wacker oxidation of olefins catalyzed by a cobalt complex catalyst, the method comprising: using 1,2-disubstituted olefins of Formula I as raw materials, using atmospheric air as oxygen source, using SPODA•Co complex as catalyst, and using silane compounds as hydrogen source, to obtain organic ketone compounds of Formula II.

[0009]

[0010] I II

[0011] The reaction formula of this invention can be represented by the following formula:

[0012]

[0013] In formula I or formula II, R 1Choose from the following groups that are either unsubstituted or substituted by one or more substituents A: C2-C10 alkyl, C3-C10 cycloalkyl, C6-C20 aromatic, and C4-C20 heterocyclic aryl;

[0014] The substituent A is any one or more of the following: C1-C10 alkyl, C1-C10 alkoxy, C3-C10 cycloalkyl, ester, halogen, C1-C10 alkylthio, C6-C20 aromatic, C4-C20 heterocyclic aryl, benzyloxy, tert-butyldimethylsiloxy, trifluoromethyl, dimethylamino, pinacolboryl ester, dextrorotatory borneoloxy, citronelloloxy, mentholoxy, or geranioloxy;

[0015] The aromatic group of C6-C20 is preferably phenyl, naphthyl, or estradiol, and the heterocyclic aryl group of C4-C20 is pyridyl, pyrroleyl, indolyl, benzodioxazolyl, benzoxazolyl, furanyl, or thiopheneyl.

[0016] The substituents on the phenyl group are preferably one or more of C1-C3 alkyl, C1-C3 alkoxy, halogen, or C1-C3 alkylthio groups;

[0017] R 2 H or optionally any of the following groups that are unsubstituted or substituted by one or more substituents B: C1-C10 alkyl, C2-C10 alkenyl, phenyl or benzyl;

[0018] The substituent B is any one or more of the following: C1-C10 alkyl, C1-C10 alkoxy, halogen, C1-C10 amino, C6-C20 aromatic, 1,3-dioxolane, Boc, and Boc-NH-.

[0019] Or in equation I, R 1 and R 2 The compounds are linked to form a ring, and together with an alkenyl group, form a C6-C12 cycloalkenyl group or a C9-C12 benzocycloalkenyl group; the hydrogen atoms on the C6-C12 cycloalkenyl group or the C9-C12 benzocycloalkenyl group are not substituted or are substituted by one or more substituent C groups, wherein the substituent C groups are C1-C3 alkyl groups, C1-C3 alkoxy groups, or halogens; preferably, R 1 and R 2 They are linked together to form benzocyclohexene.

[0020] Preferably, the R 1 and R 2 They are different substituents.

[0021] Furthermore, R 1Preferably, the following groups are unsubstituted or substituted with one or more substituents A: C2-C10 alkyl, phenyl, naphthyl, estradiol, pyridyl, pyrroleyl, indolyl, benzodioxazolyl, benzoxazolyl, furanyl or thiopheneyl;

[0022] The substituent A is preferably one or more of the following: C1-C3 alkyl, C1-C3 alkoxy, C1-C10 ester, halogen, C1-C3 alkylthio, phenyl, naphthyl, heterocyclic aryl, benzyloxy, tert-butyldimethylsiloxy, trifluoromethyl, dimethylamino, pinacolboryl ester, dextrorotatory borneoloxy, citronelloloxy, mentholoxy, or geranioloxy; the heterocyclic aryl is preferably indolyl, pyridyl, pyrroleyl, thiophenyl, or furanyl.

[0023] More preferably, the R 1 It is a C2-C8 alkyl, naphthyl, 6-methoxynaphthyl, pyridyl, 2-methoxypyridyl, indole, N-methylindole, benzodioxazolyl, group shown in Formula III, or group shown in Formula g;

[0024] III

[0025] In the group represented by Formula III, R 4 R 5 R 6 R 7 R 8 R is selected from any one of H, halogen, C1-C2 alkyl, C1-C3 alkoxy, benzyloxy, C1-C3 alkylthio, tert-butyldimethylsiloxy, trifluoromethyl, dimethylamino, pinacolboryl ester, dextroborneoloxy, citronelloloxy, mentholoxy, or geranioloxy. 4 R 5 R 6 R 7 R 8 When all atoms are hydrogen (H), Formula III represents a phenyl group; the halogen is F, Cl, or Br.

[0026] g

[0027] The R 1 In the middle, R 1 When it is a C2-C8 alkyl group, the H on the C2-C8 alkyl group is not substituted or is substituted by substituent A; when the H on the C2-C8 alkyl group is substituted by substituent A, R 1 It can be represented as R A —(CH2)n—, where n is an integer from 2 to 8, R A Substituents A and R on the carbon chain APreferably, it is phenyl, naphthyl, p-methoxyphenyl or aryl carbamate group.

[0028] R 2 Preferably, it is H, or the following groups that are unsubstituted or substituted by one or more substituents B: C1-C8 alkyl, C2-C8 alkenyl, phenyl or benzyl;

[0029] The substituent B is preferably any one or more of C1-C5 alkyl, halogen, C1-C5 amino, phenyl, substituted phenyl, 1,3-dioxolane, Boc, and Boc-NH-.

[0030] More preferably R 2 It is H, a C1-C6 alkyl group, a C2-C6 alkenyl group, a phenyl group, or a benzyl group; the H on the C1-C6 alkyl group is not substituted or is substituted by a substituent B, R 2 When the alkyl group is a C1-C6 alkyl group and the H on the alkyl group is replaced by a substituent B, R 2 It can be represented as R B —(CH2)m—, where m is an integer from 1 to 6, and the substituent B is preferably phenyl, C1-C3 amino, 4-methoxyphenyl, 1,3-dioxolanecycloyl, Boc, or Boc-NH-.

[0031] In the method of this invention, the silane compound is diphenylsilane (Ph2SiH2) or polymethylhydrosiloxane (PMHS).

[0032] As a further improvement, an organic solvent is added to the synthesis method of the present invention. The organic solvent is any one of benzene, carbon tetrachloride, toluene, tetrahydrofuran, diethyl ether, dichloromethane, acetonitrile, dioxane, petroleum ether, cyclohexane, n-hexane, ethyl acetate, chloroform, and N,N-dicarboxamide, preferably toluene or tetrahydrofuran.

[0033] The amount of organic solvent used is generally 0.1 to 10 mL / mmol, calculated based on the amount of the disubstituted olefin shown in Formula I.

[0034] This invention uses atmospheric pressure air as the oxygen source, and the reaction flask can be directly exposed to the air.

[0035] As a further improvement, the molar ratio of the disubstituted olefin, SpODA•Co complex, and silane compound represented by Formula I in this invention is 1:0.00001-0.1:1.0-2.0, preferably 1:0.001~0.05:1.0.

[0036] The reaction temperature of this invention is 0 ℃ to room temperature.

[0037] The reaction time is 0.5 to 5 hours, preferably 1 to 1.5 hours.

[0038] As a further improvement, after the reaction of the present invention is completed, the crude product is post-processed to obtain the organic ketone compound represented by formula II. The post-processing means includes one or more of thin-layer chromatography, column chromatography or vacuum distillation, preferably column chromatography.

[0039] Furthermore, after the reaction was completed, petroleum ether was added, and the reaction was quenched by stirring under air. The crude product was then post-treated to obtain the organic ketone compound shown in Formula II.

[0040] The catalyst used in this invention, the SpODA•Co complex, is a cobalt complex of a salicylaldehyde diamine oxazoline compound, and is an optically pure compound of formula IV or its enantiomer or racemate.

[0041]

[0042] IV

[0043] R 11 R 12 Each of the following is an independent H, unsubstituted or substituted with 1-2 C1-C4 alkoxy groups. 12 Alkyl groups, unsubstituted or substituted with 1-3 substituents (a), C5-C 12 The aryl group a is a cycloalkyl group, or an unsubstituted or aryl group a substituted with 1-3 substituents b; the aryl group a is benzyl, phenyl, or naphthyl; the substituent a is a C1-C4 alkyl or C1-C4 alkoxy; the substituent b is a C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F, or Cl;

[0044] R 13 R 14 Each is independently a C1-C alkoxy group that is either unsubstituted or substituted with 1-2 C1-C4 alkoxy groups. 12 Alkyl groups, unsubstituted or substituted with 1-3 substituents (a), C5-C 12 Cycloalkyl groups, or unsubstituted or aryl a groups substituted with 1-3 substituents b;

[0045] R 15 R 16 R 17 R 18 Each is independent of H, C1-C 12 Alkyl, C1-C4 fluoroalkoxy, F, Cl, nitro, or unsubstituted or substituted with 1-3 substituents a, of C5-C12 cycloalkyl groups;

[0046] R 19 R 20 R 21 R 22Each is independent of H, C1-C 12 Alkyl, C1-C4 fluoroalkoxy, F, Cl, nitro, or unsubstituted or substituted with 1-3 substituents a, of C5-C12 cycloalkyl groups;

[0047] R 23 H, unsubstituted or C1-C4 substituted with 1-2 C1-C4 alkoxy groups 12 Alkyl groups, unsubstituted or substituted with 1-3 substituents (a), C5-C 12 The cycloalkyl group, or the unsubstituted or aryl b group substituted with 1-3 substituents b; wherein the aryl b group is phenyl or naphthyl;

[0048] R 24 R 25 R 26 R 27 Each of the following is independently H, an unsubstituted or C1-C12 alkyl group or substituted with 1-2 C1-C4 alkoxy groups, a C1-C12 alkoxy group, a C1-C4 fluoroalkoxy group, F, Cl, Br, a nitro group, or an unsubstituted or C5-C12 cycloalkyl group or substituted with 1-3 substituents a.

[0049] In Formula IV, X is O or S, preferably O.

[0050] Furthermore, the catalyst SpODA•Co complex is preferably a compound represented by Formula IV, wherein R 11 It is a C1-C12 alkyl, phenyl, or benzyl group; R 12 It is H or C1-C12 alkyl;

[0051] R 13 R 14 Each is independently H or C1-C12 alkyl;

[0052] R 15 R 16 R 17 R 18 Each is independently H or C1-C12 alkyl;

[0053] R 19 R 20 R 21 R 22 Each is independently H or C1-C12 alkyl;

[0054] R 23 It is H or C1-C12 alkyl;

[0055] R 24 R 25 R 26 R 27Each can be independently H, C1-C12 alkyl, C1-C12 alkoxy, F, Cl, or Br;

[0056] X is O.

[0057] More preferably R 11 R 12 Each can be methyl, propyl, phenyl, or benzyl, R 13 R 14 R 15 R 16 R 17 R 18 R 19 R 20 R 21 R 22 R 23 R 24 R 26 All are H; R is preferred. 25 R 27 Each of the following is independently H, a C1-C4 alkyl group, a methoxy group, or a bromine; X is O.

[0058] Furthermore, the tetradentate ligand cobalt metal complex SpODA•Co is preferably as shown in Formula IV-1 or IV-2:

[0059]

[0060] IV-1 IV-2

[0061] In this invention, the compound represented by Formula IV can be prepared by the following method:

[0062] Under nitrogen protection, the salicylaldehyde diamine phenyloxazoline compound shown in formula (1) and cobalt salt CoX2 are reacted in an organic solvent for 1 to 10 hours to prepare the metal complex shown in formula IV; the organic solvent is methanol or ethanol.

[0063] (1)

[0065] R in equation (1) 11 ~R 27 As previously stated.

[0066] The molar ratio of the salicylaldehyde diamine phenyloxazoline compound shown in formula (1) to the cobalt salt CoX2 is 0.9~2.2:1, preferably 0.9~1.1:1, and more preferably 1~1.1:1.

[0067] The synthesis of the metal compound shown in Formula IV can be carried out at low or high temperatures, such as -20 to 150°C, preferably at 85°C.

[0068] The salicylaldehyde diamine phenyloxazoline compound shown in formula (1) can be prepared by the following method:

[0069] (a) Under nitrogen protection, the 2-oxazolinylbromobenzene compound shown in formula (2) and the diamine compound shown in formula (3) undergo a coupling reaction in the presence of a catalyst to obtain the compound shown in formula (4);

[0070] (b) Under nitrogen protection, the compound shown in formula (4) undergoes a condensation reaction with the salicylaldehyde compound shown in formula (5) to obtain the salicylaldehyde diamine oxazoline compound shown in formula (1).

[0071] (2) (3) (4)

[0072] (5)

[0073] R in equations (2), (3), (4), and (5) 11 ~R 27 As previously stated.

[0074] The catalyst in step (a) is a transition metal salt, an organophosphorus ligand, or an inorganic base.

[0075] Furthermore, the transition metal salt is a metal salt of Ru, Rh, Pd, or Ir, preferably dichlorotriphenylphosphine palladium;

[0076] The inorganic base may be sodium tert-butoxide or potassium tert-butoxide, preferably sodium tert-butoxide;

[0077] The organophosphine ligand may be triphenylphosphine, tricyclohexylphosphine, 1,2-bis(diphenylphosphine)ethane, or 1,1'-bis(diphenylphosphine)ferrocene, preferably 1,1'-bis(diphenylphosphine)ferrocene.

[0078] The reaction in step (a) is preferably carried out in an organic solvent, which is any one of benzene, carbon tetrachloride, petroleum ether, tetrahydrofuran, dimethylformamide, diethyl ether, dichloromethane, chloroform, toluene, xylene, cyclohexane, n-hexane, n-heptane, dioxane, and acetonitrile, preferably toluene.

[0079] The volume of the organic solvent used in step (a) is 2 to 10 mL / mmol, calculated as the amount of substance of the compound represented by formula (2).

[0080] As a further improvement, the reaction temperature of the coupling reaction in step (a) is from -0 °C to 150 °C, preferably heated to reflux for the reaction time of 1 hour to 48 hours.

[0081] As a further improvement, in step (a) of the present invention, the molar ratio of the 2-oxazolinylbromobenzene compound shown in formula (2), the diamine compound shown in formula (3), the transition metal inorganic salt, the organophosphine ligand, and the inorganic base is 1:1~5:0.01~1:0.02~2:2~10, preferably 1:1~3:0.01~0.1:0.02~0.1:2~4.

[0082] In step (a), after the reaction is completed, the reaction solution is post-treated to obtain the compound shown in formula (4). The post-treatment method is as follows: the reaction solution is cooled to room temperature, filtered, washed with dichloromethane, concentrated, and then separated by column chromatography to obtain the compound shown in formula (4). The eluent used for column chromatography is a mixed solvent of petroleum ether and ethyl acetate.

[0083] In step (b), the molar ratio of the compound shown in formula (4) to the salicylaldehyde compound shown in formula (5) is 1:1 to 10, preferably 1:1 to 5, and more preferably 1:1 to 2.

[0084] Step (b) may or may not involve adding a catalyst. When a catalyst is added, the catalyst may be a protic acid or a molecular sieve, and the amount of the catalyst used is 1 to 5% of the amount of the compound shown in formula (4).

[0085] Preferred step (b) does not involve adding a catalyst.

[0086] The reaction solvent in step (b) is an organic solvent, preferably methanol or ethanol, more preferably ethanol. The volume of the reaction solvent in step (b) is 2 to 10 mL / mmol, calculated as the amount of the compound represented by formula (4).

[0087] The reaction temperature in step (b) is heated to reflux, and the reaction time is 15 to 30 hours.

[0088] After the reaction in step (b) is completed, the reaction solution is post-treated to obtain the salicylaldehyde diamine oxazoline compound shown in formula (1). The post-treatment method is as follows: the reaction solution is cooled to room temperature, filtered, the filtrate is washed, concentrated, and then separated by column chromatography to obtain the salicylaldehyde diamine oxazoline compound shown in formula (1).

[0089] The present invention provides an efficient method for synthesizing high-value-added organic ketone compounds with high chemoselectivity from 1,2-disubstituted alkenes and ambient air, using SpODA•Co complexes as catalysts, silane compounds as hydrogen sources, and silane compounds as hydrogen sources.

[0090] Compared to existing Wacker-type oxidation reactions of olefins, this method is applicable to a variety of different types of olefins, exhibiting good activity and chemoselectivity. The reaction system can tolerate the presence of thioether groups in the substrate, preventing the thioether groups from being oxidized during the reaction. Furthermore, for internal olefin substrates, this invention shows significant advantages in conversion and selectivity. The olefin substrate synthesis method of this invention is simple and inexpensive. The reaction conditions of this invention are mild, the operation is simple, and the reaction is highly efficient, achieving complete conversion of the substrate olefin in just one hour. In addition, the reaction does not require the addition of any other toxic transition metal salts (such as ruthenium, rhodium, palladium, etc.), making it of great practical application value in pharmaceutical and materials synthesis. This invention utilizes an asymmetric tetradentate NNNO tetradentate ligand cobalt catalyst to selectively oxidize various olefin feedstocks using Wacker-type oxidation reactions. The conversion rate of this invention is also good, generally reaching >99%, and the chemoselectivity is also high, with the yield of the organic ketone product typically ranging from 70% to 99%. Detailed Implementation

[0091] The technical solution of the present invention will be further described in detail below through specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0092] The catalyst used in the examples is shown below, the compound represented by Formula IV, abbreviated as SPODA•Co.

[0093] The preferred amount of the metal complex is 0.001-10 mol%, more preferably 0.1-5 mol%.

[0094] The CCDC number for the single crystal structure of Formula IV-2 is 2241803.

[0095] The catalyst synthesis route is as follows:

[0096]

[0097] The specific synthesis steps of the catalyst are as follows: the diamine compound shown in formula (3) and the salicylaldehyde compound shown in formula (5) are commercially available, and the 2-bromophenyloxazoline compound shown in formula (2) is prepared according to the literature (Göbel, D.; Rusch, P.; Duvinage, D.; Stauch, T.; Bigall, N.-C.; Nachtsheim, BJJ Org. Chem.2021, 86, 14333–14355.).

[0098] Preparation of 2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)bromobenzene(2)-S

[0099] Under nitrogen protection, zinc trifluoromethanesulfonate (2.9116 g, 8.0 mmol, 0.2 equiv) was added to a 100 mL two-necked flask and dried under vacuum using a hot air gun. After cooling to room temperature, o-bromobenzonitrile (7.2864 g, 40.0 mmol, 1.0 equiv), 2-amino-2-methyl-1-propanol (4.2849 g, 48.0 mmol, 1.2 equiv), and toluene (40 mL) were added sequentially. The reaction was stirred at 110 °C for 12 h, cooled to room temperature, filtered through silica gel, washed with dichloromethane, and then the filtrate was concentrated to obtain a pale yellow liquid. The liquid was separated by column chromatography to obtain a colorless liquid, 2-bromophenylgesdimethyloxazoline, 8.2385 g (32.4 mmol, 81% yield). 1 H NMR (400 MHz, CDCl3) δ 7.60 (dd, J = 7.6, 1.5Hz, 1 H), 7.55 (dd, J = 7.8, 0.7 Hz, 1 H), 7.27 (dt, J =14.2, 7.5, 0.7 Hz, 1H), 7.20 (dt, J = 13.7, 7.8, 1.6 Hz, 1 H), 4.09 (s, 2 H), 1.35 (s, 6 H); and [Lei, Z.-Q.; Pan, F.; Li, H.; Li, Y.; Zhang, X.-S.; Chen, K.; Wang, X.; Li,Y.-X.; Sun, J.; Shi, Z.-JJ Am. Chem. Soc. 2015, 137, The product data reported in 5012–5020 are consistent.

[0100] Preparation of oxazoline diamine compound (4)-S

[0101] Under a nitrogen atmosphere, 2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)bromobenzene (2.5492 g, 10 mmol, 1.0 equiv.), phenylenediamine (2.1602 g, 20 mmol, 2.0 equiv.), Pd(PPh3)2Cl2 (0.2881 g, 0.25 mmol, 2.5 mol%), 1,1'-bis(diphenylphosphine)ferrocene (0.2706 g, 0.50 mmol, 5.0 mol%), sodium tert-butoxide (1.93 g, 20 mmol, 2.0 equiv.), and toluene (20 mL, 0.5 M) were reacted at 110 °C for 12 hours. After the reaction was complete, the mixture was cooled to room temperature, filtered, washed with dichloromethane, concentrated, and then subjected to column chromatography with a petroleum ether:ethyl acetate volume ratio of 5:1. Elution yielded 2.0820 g (7.4 mmol, 74% yield) of the target product. The product was a white solid. MPa 113.4–114.5 o C; IR (neat): 3455, 3366, 2968, 1629, 1504cm -1 ; 1 H NMR: (400 MHz, CDCl3) δ 9.90 (s, 1H), 7.76 (t, J = 8.0 Hz, 1H), 7.22-7.16 (m, 2H), 7.06 (t, J = 7.6 Hz, 1H), 6.86-6.72 (m, 2H), 6.70-6.63 (m, 2H), 4.02 (s, 2H), 3.85 (s, 2H), 1.36 (s, 6H); 13 C NMR: (100 MHz, CDCl3) δ 162.2,147.3, 143.1, 132.0, 129.5, 127.5, 126.7, 126.5, 118.6, 116.0, 115.7, 112.5,109.5, 77.4, 67.8, 28.7; HRMS (ESI) calculated for [C 17 H 20 N3O] + (M+H + ) requires m / z 282.1601, found m / z 282.1600.

[0102] Synthesis of ligand SPODA

[0103] Oxazoline diamine compound (4)-S (0.8447 g, 3.0 mmol, 1.0 equiv.) and 3,5-di-tert-butylsalicylaldehyde (0.7029 g, 3.0 mmol, 1.0 equiv.) were reacted in 8 mL of ethanol at boiling point for 12 h. After the reaction was completed, the mixture was cooled to room temperature, concentrated under reduced pressure, and separated by column chromatography using petroleum ether:ethyl acetate (20:1 v / v) to give 1.2840 g (2.6 mmol, 86% yield) of the target product. The product was a yellow solid. Mp 74.1-75.2 o C; IR (neat): 2960, 1633, 1586, 1464, 1282 cm -1 ; 1 H NMR: (400 MHz, CDCl3) δ13.12 (s, 1H), 10.44 (s, 1H), 8.58 (s, 1H), 7.78 (m, 2H), 7.42 (s, 1H), 7.39(d, J = 8.0 Hz, 1H), 7.27 (t, J = 8.0 Hz, 1H), 7.21 (d, J = 8.0 Hz, 1H), 7.19(s, 1H), 7.10 (d, J = 7.6 Hz, 1H), 7.05 (t, J = 7.6 Hz, 1H), 6.78 (t, J = 7.6Hz, 1H), 3.92 (s, 2H), 1.41 (s, 9H), 1.32 (s, 9H), 1.11 (s, 6H); 13 C NMR: (100MHz, CDCl3) δ 165.3, 161.5, 158.0, 144.7, 142.0, 140.3, 136.7, 135.3, 131.5,129.8, 127.9, 126.8, 126.63, 122.58, 120.1, 119.6, 118.6, 117.5, 114.4,112.0, 77.4, 67.7, 35.0, 34.1, 31.4, 29.4, 28.4; HRMS (ESI) calculated for[C 32 H 40 N3O2] + (M+H + ) requires m / z 498.3115, found m / z 498.3114.

[0104] Synthesis of Catalyst IV-1:

[0105] In a 50 mL dry reaction tube, Co(OAc)₂ (0.2546 g, 1.44 mmol, 0.95 equiv.), the ligand SpODA (0.7469 g, 1.5 mmol, 1.0 equiv.), and anhydrous ethanol (3.0 mL, 0.5 M) were added under nitrogen atmosphere. The reaction system was heated to 85 °C. o The mixture was stirred at C for 12.0 h. After the reaction was complete, it was returned to room temperature, filtered, and the solution was distilled using anhydrous ethanol (-40). o C) After washing, the product was dried using a vacuum oil pump to obtain 0.7893 g (1.42 mmol, 91% yield) of the target product as a red solid. HRMS (ESI) calculated for [C 32 H 38 CoN3O2] + (M+H + Formula IV-2 requires m / z 555.2291, found m / z 555.2285. It is prepared by complexing the corresponding ligand with cobalt acetate.

[0106]

[0107] IV-1 IV-2

[0108] Example 1: Cobalt-catalyzed Wacker-type oxidation of aryl olefins

[0109] Standard conditions:

[0110] A PTFE magnetic stir bar was added to a 25 mL Schlenk reaction tube, followed by the addition of an olefin substrate (0.25 mmol, 1.0 equiv.), IV-1 (0.0125 mmol, 5 mol%), Ph2SiH2 (0.25 mmol, 0.99 g / mL, 49 µL, 1.0 equiv.), and THF (1.0 mL). After stirring at room temperature for 1.0 h, 10 mL of petroleum ether was added, and the mixture was quenched by stirring under air. The reaction solution was filtered through silica gel and washed with PE / EtOAc = 2 / 1 (20 mL × 3). The filtrates were combined and concentrated under reduced pressure. Trimethylsilylbenzene (TMSPh) was added as an internal standard, and the reaction was further analyzed by... 1 ¹H NMR was used to determine the conversion, chemoselectivity, and crude yield of the reaction. Finally, a suitable eluent was selected, and silica gel was used as the stationary phase to separate the crude product into the target compound by rapid column chromatography.

[0111] II-1: 1-(4-(tert-butyl)phenyl)ethan-1-one

[0112] Colorless liquid, 90% yield. 1 H NMR: (400 MHz, CDCl3) δ 7.90 (d, J= 8.4 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 2.59 (s, 3H), 1.34 (s, 9H); 13 C NMR: (100 MHz, CDCl3) δ 197.9, 156.8, 134.6, 128.3, 125.5, 35.1, 31.1, 26.5.

[0113] II-2: 1-(p-tolyl)ethan-1-one

[0114] Colorless liquid, 97% yield. 1 H NMR: (400 MHz, CDCl3) δ 7.86 (d, J= 8.0 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), 2.58 (s, 3H), 2.41 (s, 3H); 13 C NMR: (100.MHz, CDCl3) δ 197.8, 143.9, 134.7, 129.2, 128.4, 26.5, 21.6.

[0115] II-3: 1-(4-(trifluoromethyl)phenyl)ethan-1-one

[0116] Colorless liquid, 3-2°C, 90% yield. 1 H NMR: (400 MHz, CDCl3) δ 8.07(d, J = 8.0 Hz, 2H), 7.74 (d, J = 8.0 Hz, 2H), 2.65 (s, 3H); 13C NMR: (100MHz, CDCl3) δ 197.0, 139.7, 134.6 (q, J = 33.0 Hz), 128.7, 125.7 (q, J = 3.6Hz), 123.6 (q, J = 272.7 Hz), 26.8; 19 F NMR (376.5 MHz, CDCl3) δ -63.1.

[0117] II-4: 1-(4-fluorophenyl)ethan-1-one

[0118] Colorless liquid, 76% yield. 1 H NMR: (400 MHz, CDCl3) δ 8.02-7.96(m, 2H), 7.18-7.09 (m, 2H), 2.60 (s, 3H); 13 C NMR: (100 MHz, CDCl3) δ 196.5,165.7 (d, J = 254.0 Hz), 133.5 (d, J = 2.9 Hz), 130.9 (d, J = 9.6 Hz), 115.6(d, J = 21.3 Hz), 26.5; 19 F NMR (376.5 MHz, CDCl3) δ -105.3.

[0119] II-5: 1-(4-bromophenol)ethan-1-one

[0120] Colorless liquid, 80% yield. 1 H NMR: (400 MHz, CDCl3) δ 7.82 (d, J= 8.4 Hz, 2H), 7.60 (d, J = 8.4 Hz, 2H), 2.58 (s, 3H); 13 C NMR: (100 MHz, CDCl3) δ 197.0, 135.8, 131.8, 129.8, 128.2, 26.5.

[0121] II-6: 1-(4-chlorophenyl)ethan-1-one

[0122] Colorless liquid, 86% yield. 11H NMR: (400 MHz, CDCl3) δ 7.90 (d, J =8.8 Hz, 2H), 7.44 (d, J = 8.8 Hz, 2H), 2.59 (s, 3H); 13 13C NMR: (100 MHz, CDCl3)δ 196.8, 1,39.6, 135.4, 129.7, 128.9, 26.5.

[0123] II-7: 4-acetylbiphenyl

[0124] Colorless liquid, 78% yield. 1 1H NMR: (400 MHz, CDCl3) δ 8.04 (d, J= 8.0 Hz, 2H), 7.69 (d, J = 8.0 Hz, 2H), 7.63 (d, J = 7.2 Hz, 2H), 7.48 (t, J= 7.2 Hz, 2H), 7.40 (t, J = 7.2 Hz, 1H), 2.64 (s, 3H); 13 13C NMR: (100 MHz,CDCl3) δ 197.7, 145.7, 139.8, 135.8, 128.9, 128.2, 127.4, 127.2, 127.0, 26.6.

[0125] II-8: 1-(4-(methylthio)phenyl)ethan-1-one

[0126] Colorless liquid 3-2h (0.13 mmol, >20 / 1 cr, 51% yield). 1 1H NMR:(400 MHz, CDCl3) δ 7.86 (d, J = 8.0 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), 2.57(s, 3H), 2.52 (s, 3H); 13 13C NMR: (100 MHz, CDCl3) δ 197.1, 145.8, 133.4, 128.7,124.9, 26.4, 14.7.

[0127] II-9: 当1-(4-methoxyphenyl)ethan-1-one

[0128] Colorless liquid, 74% yield. 1 H NMR: (400 MHz, CDCl3) δ 7.94 (d,J = 8.8 Hz, 2H), 6.94 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H), 2.56 (s, 3H); 13 CNMR: (100 MHz, CDCl3) δ 196.6, 163.4, 130.5, 130.2, 113.6, 55.3, 26.2.

[0129] II-10: 1-(3-chlorophenyl)ethan-1-one

[0130] Colorless liquid, 97% yield. 1 H NMR: (400 M Hz, CDCl3) δ 7.93 (s,1H), 7.83 (d, J = 7.6 Hz, 1H), 7.54 (d, J = 7.6 Hz, 1H), 7.41 (t, J = 7.6 Hz,1H), 2.60 (s, 3H); 13 C NMR: (100 MHz, CDCl3) δ 196.7, 138.6, 134.9, 133.0,129.9, 128.4, 126.4, 26.6.

[0131] II-11: 1-(m-tolyl)ethan-1-one

[0132] Colorless liquid, 80% yield. 1 H NMR: (400 MHz, CDCl3) δ 7.80-7.73(m, 2H), 7.40-7.32 (m, 2H), 2.59 (s, 3H), 2.42 (s, 3H); 13 C NMR: (100 MHz, CDCl3) δ 198.4, 138.4, 137.2, 133.9, 128.8, 128.4, 125.6, 26.7, 21.3.

[0133] II-12: 1-(2-methoxyphenyl)ethan-1-one

[0134] Pale yellow solid, 61% yield. 1 H NMR: (400 MHz, CDCl3) δ 7.73 (dd, J= 7.6, 1.6 Hz, 1H), 7.47 (dt, J = 7.6, 1.6 Hz, 1H), 7.40-7.32 (m, 2H), 3.92(s, 3H), 2.62 (s, 3H); 13 C NMR: (100 MHz, CDCl3) δ 199.9, 158.9, 133.6, 130.4,128.3, 120.5, 111.5, 55.5, 31.8.

[0135] II-13: 1-(3-fluoro-4-methoxyphenyl)ethan-1-one

[0136] White solid, 98% yield. 1 H NMR: (400 MHz, CDCl3) δ 7.61 (dd,J = 8.4, 2.0 Hz, 1H), 7.56-7.50 (m, 1H), 7.14 (dd, J = 10.8, 8.4 Hz, 1H), 3.95 (s, 3H), 2.59 (s, 3H); 13 C NMR: (100 MHz, CDCl3) δ 196.6, 155.6 (d, J =154.43 Hz), 148.0 (d, J = 11.2 Hz), 133.7 (d, J = 3.4 Hz), 122.4 (d, J = 8.3Hz), 115.8 (d, J = 19.6 Hz), 112.6 (d, J = 2.9 Hz), 56.2, 26.4; 19 F NMR (376.5MHz, CDCl3) δ -127.0.

[0137] II-14: 1-(3,4-dimethylphenyl)ethan-1-one

[0138] Colorless liquid, 71% yield. 11H NMR: (400 MHz, CDCl3) δ 7.73 (s, 1H), 7.69 (d, J = 8.0 Hz, 1H), 7.21 (d, J = 8.0 Hz, 1H), 2.57 (s, 3H), 2.32 (s, 6H); 13 13C NMR: (100 MHz, CDCl3) δ​​​​​​​​​​​​​​​​​​​​​CNMR: (100 MHz, CDCl3) δ 198.1, 135.6, 134.5, 132.5, 130.2, 129.5, 128.43,128.38, 127.7, 126.7, 123.9, 26.6.

[0143] II-17: 1-(6-methoxypyridin-3-yl)ethan-1-one

[0144] White solid, 87% yield. 1 H NMR: (400 MHz, CDCl3) δ 8.78 (s,1H), 8.14 (d, J = 8.8 Hz, 1H), 6.79 (d, J = 8.8 Hz, 1H), 4.01 (s, 3H), 2.57(s, 3H); 13 C NMR: (100 MHz, CDCl3) δ 195.6, 166.7, 149.4, 138.1, 126.9, 111.1,54.0, 26.3.

[0145] II-18: 1-(4-methoxyphenyl)propan-1-one

[0146] Colorless liquid, 64% yield. 1 H NMR: (400 MHz, CDCl3) δ 7.95 (d,J = 8.4 Hz, 2H), 6.93 (d, J = 8.4 Hz, 2H), 3.86 (s, 3H), 2.95 (q, J = 7.2 Hz,2H), 1.21 (t, J = 7.2 Hz, 3H); 13 C NMR: (100 MHz, CDCl3) δ 199.4, 163.2,130.2, 130.0, 113.6, 55.4, 31.3, 8.4.

[0147] II-19: 1,2-diphenylethan-1-one

[0148] White solid 3-2s (0.10 mmol, 4 / 1 cr, 39% yield). 11H NMR: (400 MHz, CDCl3) δ 8.02 (d, J = 7.6 Hz, 2H), 7.56 (t, J = 7.6 Hz, 1H), 7.46 (t, J = 7.6 Hz, 2H), 7.33 (t, J = 7.6 Hz, 2H), 7.30 - 7.21 (m, 3H), 4.29 (s, 2H); 13 13C NMR: (100 MHz, CDCl3) δ 197.6, 136.5, 134.5, 133.2, 129.4, 128.63, 128.61, 128.59, 126.9, 45.4.

[0149] II - 20: tert - butyl (3 - oxo - 3 - phenylpropyl)carbamate II - 20:

[0150] White solid, 69% yield. 1 1H NMR: (400 MHz, CDCl3) δ 7.96 (d, J = 8.0 Hz, 2H), 7.58 (t, J = 8.0 Hz, 1H), 7.47 (t, J = 8.0 Hz, 2H), 3.55 (q, J = 5.6 Hz, 2H), 3.21 (t, J = 5.6 Hz, 2H), 1.64 (s, 1H), 1.43 (s, 9H); 13 13C NMR: (100 MHz, CDCl3) δ 199.4, 156.0, 136.6, 133.4, 128.7, 128.0, 79.2, 38.7, 35.4, 28.4.

[0151] II - 21: (8R,9S,13S,14S) - 3 - acetyl - 13 - methyl - 7,8,9,11,12,13,15,16 - octahydro - 6H - cyclopenta[a]phenanthren - 17(14H) - one

[0152] White solid, 87% yield. 1H NMR: (400 MHz, CDCl3) δ 7.73(d, J = 8.4 Hz, 1H), 7.71 (s, 1H), 7.39 (d, J = 8.4 Hz, 1H), 3.01-2.97 (m,2H), 2.58 (s, 3H), 2.56-2.43 (m, 2H), 2.35 (dt, J = 10.8, 3.6 Hz, 1H), 2.23-2.03 (m, 3H), 2.02-1.95 (m, 1H), 1.66-1.46 (m, 6H), 0.92 (s, 3H); 13 C NMR: (100 MHz, CDCl3) δ 198.1, 145.4, 136.9, 134.8, 128.9, 125.8, 125.6, 50.5,47.9, 44.7, 37.8, 35.8, 31.5, 29.3, 26.6, 26.3, 25.5, 21.5, 13.8.

[0153] Example 2: Cobalt-catalyzed Wacker-type oxidation of alkyl olefins

[0154] Standard conditions

[0155] A PTFE magnetic stir bar was added to a 25 mL Schlenk reaction tube, followed by the addition of an olefin substrate (0.25 mmol, 1.0 equiv.), IV-1 (0.0125 mmol, 5 mol%), PMHS (0.25 mmol, 1.006 g / mL, 29.8 µL, 1.0 equiv.), and THF (1.0 mL). After stirring at room temperature for 1.0 h, 10 mL of petroleum ether was added, and the mixture was quenched by stirring under air. The reaction solution was filtered through silica gel and washed with PE / EtOAc = 2 / 1 (20 mL × 3). The filtrates were combined and concentrated under reduced pressure. Trimethylsilylbenzene (TMSPh) was added as an internal standard. 1 ¹H NMR was used to determine the conversion, chemoselectivity, and crude yield of the reaction. Finally, a suitable eluent was selected, and silica gel was used as the stationary phase to separate the crude product into the target compound by rapid column chromatography.

[0156] II-22: 4-phenylbutan-2-one

[0157] Colorless liquid, 3-2 v, 69% yield. 1H NMR: (400 MHz, CDCl3) δ 7.28(t, J = 7.6 Hz, 2H), 7.22-7.16 (m, 3H), 2.90 (t, J = 7.6 Hz, 2H), 2.76 (t, J= 7.6 Hz, 2H), 2.14 (s, 3H); 13 C NMR: (100 MHz, CDCl3) δ 208.0, 141.0, 128.5,128.3, 126.1, 45.2, 30.1, 29.7.

[0158] II-23: 3-oxobutyl benzoate

[0159] Colorless liquid, 59% yield. 1 H NMR: (400 MHz, CDCl3) δ 8.01(d, J = 7.6 Hz, 2H), 7.56 (t, J = 7.6 Hz, 1H), 7.43 (t, J = 7.6 Hz, 2H), 4.59(t, J = 6.4 Hz, 2H), 2.91 (t, J = 6.4 Hz, 2H), 2.24 (s, 3H); 13 C NMR: (100MHz, CDCl3) δ 205.6, 166.4, 133.1, 129.9, 129.6, 128.4, 59.8, 42.4, 30.3.

[0160] Example 3: Comparison of Catalytic Performance and Reaction Conditions of Various Catalysts

[0161]

[0162] 7 L5•Co >99 78 3.5 / 1 1 Salen•Co 25 17 3.0 / 1 <![CDATA[2 c ]]> <![CDATA[Co(OAc) 2 + L8]]> 0 0 n.d. 3 L1•Co >99 <![CDATA[91(90) d ]]> 22 / 1 4 L2•Co >99 83 5.9 / 1 5 L3•Co >99 86 6.0 / 1 6 L4•Co >99 75 3.0 / 1. 8 L6•Co >99 84 5.2 / 1 9 L7•Co >99 76 3.2 / 1

[0163] a Reaction conditions: p-tert-butylstyrene 3-1a (0.25 mmol), diphenylsilane (1.0 equiv.), Cat. (5.0 mol%), THF (0.25 M), reaction at room temperature under air for 1 hour; b Using trimethylsilylbenzene as an internal standard, through 1 H NMR was used to identify the conversion rate, reaction yield, and selectivity of the raw materials; c Co(OAc)2 (5 mol%) and L10 (6 mol%); d Separation yield.

[0164] The results showed that the cobalt complexes L1·Co~L7·Co of salicylaldehyde diamine oxazoline compounds exhibited good conversion rates and catalytic activity. Among them, L1·Co and L3·Co showed the best yield and selectivity, which are the IV-1 and IV-2 catalysts of this invention. The ligand structures of Salen•Co and Co(OAc)2+ L8 are different from those of the salicylaldehyde diamine oxazoline compounds of this invention, and their conversion rates and yields are extremely low.

Claims

1. A method for preparing organic ketone compounds by the Wacker oxidation reaction of olefins catalyzed by a cobalt complex catalyst, characterized in that... The method is as follows: using 1,2-disubstituted olefins of Formula I as raw materials, using atmospheric air as oxygen source, and SPODA•Co complex as catalyst, and silane compounds as hydrogen source, organic ketone compounds of Formula II are prepared. I II The reaction equation is shown below: In formula I or formula II, R 1 Choose from the following groups that are either unsubstituted or substituted by one or more substituents A: C2-C10 alkyl, C3-C10 cycloalkyl, C6-C20 aromatic, and C4-C20 heterocyclic aryl; The substituent A is any one or more of the following: C1-C10 alkyl, C1-C10 alkoxy, C3-C10 cycloalkyl, ester, halogen, C1-C10 alkylthio, C6-C20 aromatic, C4-C20 heterocyclic aryl, benzyloxy, tert-butyldimethylsiloxy, trifluoromethyl, dimethylamino, pinacolboryl ester, dextrorotatory borneoloxy, citronelloloxy, mentholoxy, or geranioloxy; R 2 H or optionally any of the following groups that are unsubstituted or substituted by one or more substituents B: C1-C10 alkyl, C2-C10 alkenyl, phenyl or benzyl; The substituent B is any one or more of the following: C1-C10 alkyl, C1-C10 alkoxy, halogen, C1-C10 amino, C6-C20 aromatic, 1,3-dioxolane, Boc, and Boc-NH-. Or in equation I, R 1 and R 2 The compounds are linked to form a ring, and together with an alkenyl group, they form a C6-C12 cycloalkenyl group or a C9-C12 benzocycloalkenyl group; the H on the C6-C12 cycloalkenyl group or the C9-C12 benzocycloalkenyl group is not substituted or is substituted by one or more substituent C groups, wherein the substituent C group is a C1-C3 alkyl group, a C1-C3 alkoxy group, or a halogen.

2. The method as described in claim 1, characterized in that... The R 1 and R 2 They are different substituents; R 1 The following groups are either unsubstituted or substituted by one or more substituents A: C2-C10 alkyl, phenyl, naphthyl, estradiol, pyridyl, pyrroleyl, indolyl, benzodioxazolyl, benzoxazolyl, furanyl or thiopheneyl; The substituent A is any one or more of the following: C1-C3 alkyl, C1-C3 alkoxy, C1-C10 ester, halogen, C1-C3 alkylthio, phenyl, naphthyl, heterocyclic aryl, benzyloxy, tert-butyldimethylsiloxy, trifluoromethyl, dimethylamino, pinacolboryl ester, dextrorotatory borneoloxy, citronelloloxy, mentholoxy, or geranioloxy. R 2 The following groups are H, unsubstituted or substituted by one or more substituents B: C1-C8 alkyl, C2-C8 alkenyl, phenyl or benzyl; The substituent B is any one or more of the following: C1-C5 alkyl, halogen, C1-C5 amino, phenyl, substituted phenyl, 1,3-dioxolane, Boc, and Boc-NH-. Or R 1 and R 2 They can be linked into a ring, or linked with an alkenyl group to form benzocyclohexene.

3. The method as described in claim 2, characterized in that... The R 1 It is a C2-C8 alkyl, naphthyl, 6-methoxynaphthyl, pyridyl, 2-methoxypyridyl, indole, N-methylindole, benzodioxazolyl, group shown in Formula III, or group shown in Formula g; III In the group represented by Formula III, R 4 R 5 R 6 R 7 R 8 It may be selected from any one of H, halogen, C1-C2 alkyl, C1-C3 alkoxy, benzyloxy, C1-C3 alkylthio, tert-butyldimethylsiloxy, trifluoromethyl, dimethylamino, pinacolboryl ester, dextroborneoloxy, citronelloloxy, mentholoxy, or geranioloxy. g The R 1 In the middle, R 1 When it is a C2-C8 alkyl group, the H on the C2-C8 alkyl group is not substituted or is substituted by substituent A; when the H on the C2-C8 alkyl group is substituted by substituent A, R 1 Represented as R A —(CH2)n—, where n is an integer from 2 to 8, R A Substituents A and R on the carbon chain A It is phenyl, naphthyl, p-methoxyphenyl or aryl carbamate group; R 2 It is H, a C1-C6 alkyl group, a C2-C6 alkenyl group, a phenyl group, or a benzyl group; the H on the C1-C6 alkyl group is not substituted or is substituted by a substituent B, R 2 When the alkyl group is a C1-C6 alkyl group and the H on the alkyl group is replaced by a substituent B, R 2 Represented as R B —(CH2)m—, where m is an integer from 1 to 6, and the substituent B is phenyl, C1-C3 amino, 4-methoxyphenyl, 1,3-dioxolane, Boc, or Boc-NH-.

4. The method as described in claim 1, characterized in that... The catalyst SpODA•Co complex is a cobalt complex of a salicylaldehyde diamine oxazoline compound, and is an optically pure compound of formula IV or its enantiomer or racemate. IV In equation IV, R 11 R 12 Each of the following is an independent H, unsubstituted or substituted with 1-2 C1-C4 alkoxy groups. 12 Alkyl groups, unsubstituted or substituted with 1-3 substituents (a), C5-C 12 The aryl group a is a cycloalkyl group, or an unsubstituted or aryl group a substituted with 1-3 substituents b; the aryl group a is benzyl, phenyl, or naphthyl; the substituent a is a C1-C4 alkyl or C1-C4 alkoxy; the substituent b is a C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F, or Cl; R 13 R 14 Each is independently a C1-C alkoxy group that is either unsubstituted or substituted with 1-2 C1-C4 alkoxy groups. 12 Alkyl groups, unsubstituted or substituted with 1-3 substituents (a), C5-C 12 Cycloalkyl groups, or unsubstituted or aryl a groups substituted with 1-3 substituents b; R 15 R 16 R 17 R 18 Each is independent of H, C1-C 12 Alkyl, C1-C4 fluoroalkoxy, F, Cl, nitro, or unsubstituted or substituted with 1-3 substituents a, of C5-C12 cycloalkyl groups; R 19 R 20 R 21 R 22 Each is independent of H, C1-C 12 Alkyl, C1-C4 fluoroalkoxy, F, Cl, nitro, or unsubstituted or substituted with 1-3 substituents a, of C5-C12 cycloalkyl groups; R 23 H, unsubstituted or C1-C4 substituted with 1-2 C1-C4 alkoxy groups 12 Alkyl groups, unsubstituted or substituted with 1-3 substituents (a), C5-C 12 The cycloalkyl group, or the unsubstituted or aryl b group substituted with 1-3 substituents b; wherein the aryl b group is phenyl or naphthyl; R 24 R 25 R 26 R 27 Each of the following is independently H, an unsubstituted or C1-C12 alkyl group or substituted with 1-2 C1-C4 alkoxy groups, a C1-C12 alkoxy group, a C1-C4 fluoroalkoxy group, F, Cl, Br, a nitro group, or an unsubstituted or C5-C12 cycloalkyl group or substituted with 1-3 substituents a. In equation IV, X is O or S.

5. The method as described in claim 4, characterized in that... The catalyst SpODA•Co complex is a compound represented by formula IV, where R... 11 It is a C1-C12 alkyl, phenyl, or benzyl group; R 12 It is H or C1-C12 alkyl; R 13 R 14 Each is independently H or C1-C12 alkyl; R 15 R 16 R 17 R 18 Each is independently H or C1-C12 alkyl; R 19 R 20 R 21 R 22 Each is independently H or C1-C12 alkyl; R 23 It is H or C1-C12 alkyl; R 24 R 25 R 26 R 27 Each can be independently H, C1-C12 alkyl, C1-C12 alkoxy, F, Cl, or Br; X is O.

6. The method as described in claim 5, characterized in that... The SpODA•Co complex is shown in formula IV-1 or IV-2: IV-1 IV-2.

7. The method as described in claim 1, characterized in that... The silane compound mentioned is diphenylsilane or polymethylhydrosiloxane.

8. The method as described in claim 1, characterized in that... The synthesis method involves adding an organic solvent, which is any one of benzene, carbon tetrachloride, toluene, tetrahydrofuran, diethyl ether, dichloromethane, acetonitrile, dioxane, petroleum ether, cyclohexane, n-hexane, ethyl acetate, chloroform, and N,N-dicarboxamide.

9. The method as described in claim 1, characterized in that... The method uses atmospheric pressure air as the oxygen source, the reaction temperature is 0℃ to room temperature, and the reaction time is 0.5 to 5 hours.

10. The method as described in claim 1, characterized in that... The molar ratio of the disubstituted olefin, SpODA•Co complex, and silane compound represented by Formula I is 1:0.00001-0.1:1.0-2.0.

Images