Chiral porphyrin ligands and methods for their preparation, chiral metalloporphyrin complexes and uses

Abstract

The application relates to the technical field of synthetic chemistry, in particular to a chiral porphyrin ligand and a preparation method thereof, a chiral metal porphyrin complex and application. The molecular structure general formula of the chiral porphyrin ligand is shown as formula 1 in the description; the chiral porphyrin ligand can form a complex with metal, the performance of the complex is stable, the catalytic effect is good, for example, the complex can well catalyze the occurrence of aryl azide compounds, and therefore, the complex has a good application prospect in asymmetric organic reactions.

Description

Technical Field

[0001] This application belongs to the field of synthetic chemistry technology, and particularly relates to a chiral porphyrin ligand and its preparation method, chiral metalloporphyrin complexes and their applications. Background Technology

[0002] Inspired by enzymes in biological systems, metalloporphyrins have been shown to catalyze many important chemical transformations in biology and chemistry as enzyme mimics. These complexes have been used for atom / group transfer reactions, including oxobenzene, nitrobenzene, and carbene transfer reactions, providing efficient synthetic pathways for the direct acquisition of complex and functionally diverse compounds from abundant and inexpensive alkenes and alkanes. To enhance the catalytic power and specificity of these "synthetic enzymes," researchers have been working to "design" compounds based on proven and highly efficient bio / chemical scaffolds. Linking these chiral peripherally modified compounds to metalloporphyrin frameworks provides researchers with scaffold structures for directly manipulating the stereoselectivity of reaction systems.

[0003] Three methods have been developed to synthesize these derivatives: (1) porphyrins formed by the classical condensation of chiral aldehydes with pyrroles; (2) porphyrins formed by linking chiral structural units to amino- or hydroxyl-substituted tetraphenylporphyrins; and (3) bridging the enantiomeric surfaces of pre-chiral porphyrins to provide a chiral environment. The porphyrins prepared by these methods provide important information about the type of chiral environment required to induce enantioselectivity when used as catalysts. Research trends indicate that the harder the chiral environment, the greater the catalytic stability and the slower the intramolecular decomposition, which in turn provides a longer catalytic lifetime and a higher turnover number (TON). Conversely, more flexible substituents are more prone to degradation, such as oxidation of the porphyrin periphery, leading to a reduction in enantioselective products. Summary of the Invention

[0004] The purpose of this application is to provide a chiral porphyrin ligand, its preparation method, chiral metal porphyrin complexes, and their applications, aiming to provide more chiral porphyrin ligands and metal complexes with good catalytic effects.

[0005] To achieve the above-mentioned objectives, the technical solution adopted in this application is as follows:

[0006] In a first aspect, this application provides a chiral porphyrin ligand, the general molecular structure of which is shown in Formula 1:

[0007]

[0008] in,

[0009] X = Y = H,

[0010] or

[0011] Ar1 = Ar2 = HX = Alkyl

[0012] R1 and R2 are the same or different alkyl groups.

[0013] Secondly, this application provides a method for preparing the above-mentioned chiral porphyrin ligand, comprising the following steps:

[0014] The compound shown in Formula 2 is subjected to a first chemical reaction with the compound shown in Formula 3 to obtain the compound shown in Formula 4; the compound shown in Formula 4 is subjected to a second chemical reaction with the compound shown in Formula 5;

[0015] or,

[0016] The compound shown in Formula 6 is subjected to a third chemical reaction with the compound shown in Formula 7 to obtain the compound shown in Formula 8a; the compound shown in Formula 8a is subjected to a fourth chemical reaction with the compound shown in Formula 9 to obtain the compound shown in Formula 10a; the compound shown in Formula 10a is subjected to a first deesterification reduction to obtain the compound shown in Formula 11; the compound shown in Formula 11 is subjected to a fifth chemical reaction with the compound shown in Formula 5.

[0017] or,

[0018] The compound shown in Formula 2 is subjected to a sixth chemical reaction with the compound shown in Formula 7 to obtain the compound shown in Formula 8b; the compound shown in Formula 8b is subjected to a seventh chemical reaction with the compound shown in Formula 9 to obtain the compound shown in Formula 10b; the compound shown in Formula 10b is subjected to a second deesterification reduction.

[0019]

[0020] Thirdly, this application provides a chiral metalloporphyrin complex, comprising a chiral porphyrin ligand containing a metal ion and coordinated to the metal ion, and / or a chiral porphyrin ligand prepared by the above preparation method.

[0021] Fourthly, this application also provides the application of the above-mentioned chiral metal porphyrin complex as a catalyst in the catalytic C(sp3)-H amination reaction.

[0022] The chiral porphyrin ligands of Formula 1 provided in the first aspect of this application are derived from chiral porphyrin ligands by substituting specific substituents into the porphyrin host structure. These chiral porphyrin ligands can form complexes with metals, exhibit stable performance and good catalytic effect, for example, they can effectively catalyze the formation of aryl azide compounds. Therefore, they have great application prospects in asymmetric organic reactions.

[0023] The second aspect of this application provides a method for preparing the chiral porphyrin ligand shown in Formula 1, which can synthesize this type of chiral porphyrin ligand through three different process flows. The process is simple, can be industrialized, and has good application prospects in the field of chiral porphyrin ligand synthesis.

[0024] The chiral metal porphyrin complexes provided in the third aspect of this application contain chiral porphyrin ligands unique to this application, and therefore can stably and efficiently catalyze asymmetric organic reactions, such as the formation of aryl azide compounds, and thus have good application prospects in the field of catalysts.

[0025] The application of the chiral metal porphyrin complex provided in the fourth aspect of this application is based on the fact that the chiral metal porphyrin complex can stably and efficiently catalyze asymmetric organic reactions and can be used as a catalyst for catalyzing C(sp3)-H amination reactions. Detailed Implementation

[0026] To make the technical problems, technical solutions, and beneficial effects of this application clearer, the following detailed description is provided in conjunction with embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application.

[0027] In this application, the term "and / or" describes the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent: A alone, A and B simultaneously, or B alone. A and B can be singular or plural. The character " / " generally indicates that the preceding and following related objects have an "or" relationship. The terms "first," "second," etc., are used for descriptive purposes only to distinguish objects, such as substances, from one another, and should not be construed as indicating or implying relative importance or implicitly specifying the number of indicated technical features. For example, without departing from the scope of the embodiments of this application, "first XX" can also be referred to as "second XX," and similarly, "second XX" can also be referred to as "first XX." Thus, features defined with "first" or "second" can explicitly or implicitly include one or more of that feature.

[0028] The first aspect of this application provides a chiral porphyrin ligand with the general structural formula shown in Formula 1:

[0029]

[0030] when X = Y = H, which is... At this time, there are two types of equation 1a, that is, the structure of Ar2 can be (1S,4R,5R,8S) or (1R,4S,5S,8R).

[0031] When Ar1 = Ar2 = HX = alkyl That is

[0032] When Ar1 = Ar2 = HX = alkyl That is At this point, the molecular structure of Y in Equation 1c can be (1S, 4R, 5R, 8S).

[0033] In the above Formula 1 (i.e. Formula 1a, Formula 1b, Formula 1c), X, R1, and R2 are the same or different alkyl groups, and the selection of X, R1, and R2 is based on the formation of chiral porphyrin ligands.

[0034] Specifically, when the general molecular structure shown in Formula 1 is Formula 1a (in which case X = Y = H), R1 in the Ar1 structure of Formula 1 is an alkyl group with 1 to 10 carbon atoms, and R2 is an alkyl group with 1 to 10 carbon atoms, such as methyl, ethyl, propyl, butyl, etc. In one embodiment, R1 and R2 are methyl.

[0035] Specifically, when the general molecular structure shown in Formula 1 is Formula 1b or Formula 1c (in which case Ar1 = Ar2 = H), X is an alkyl group with 1 to 10 carbon atoms, such as methyl, ethyl, propyl, butyl, etc.; wherein when the general molecular structure shown in Formula 1 is Formula 1b, R1 in the Y structure of Formula 1 is an alkyl group with 1 to 10 carbon atoms, and R2 is an alkyl group with 1 to 10 carbon atoms, such as methyl, ethyl, propyl, butyl, etc. In one embodiment, X, R1, and R2 are methyl.

[0036] The chiral porphyrin ligands derived from the above-mentioned porphyrin host structure by substituting specific substituents can form complexes with metals. They are stable and have good catalytic effects, such as being able to catalyze the formation of aryl azide compounds. Therefore, they have good applications in asymmetric organic reactions.

[0037] The second aspect of this application provides a method for preparing the above-mentioned chiral porphyrin ligand, including three schemes, as follows:

[0038] The compound shown in Formula 2 is subjected to a first chemical reaction with the compound shown in Formula 3 (i.e., 5-(2,6-dibromo)phenyl dipyrrolidine) to obtain the compound shown in Formula 4; the compound shown in Formula 4 is subjected to a second chemical reaction with the compound shown in Formula 5 to obtain the chiral porphyrin ligand shown in Formula 1a.

[0039] Alternatively, the compound shown in Formula 6 is subjected to a third chemical reaction with the compound shown in Formula 7 to obtain the compound shown in Formula 8a; the compound shown in Formula 8a is subjected to a fourth chemical reaction with the compound shown in Formula 9 to obtain the compound shown in Formula 10a; the compound shown in Formula 10a is subjected to a first deesterification reduction to obtain the compound shown in Formula 11; and the compound shown in Formula 11 is subjected to a fifth chemical reaction with the compound shown in Formula 5 to obtain the chiral porphyrin ligand shown in Formula 1b.

[0040] Alternatively, the compound shown in Formula 2 is subjected to a sixth chemical reaction with the compound shown in Formula 7 to obtain the compound shown in Formula 8b; the compound shown in Formula 8b is subjected to a seventh chemical reaction with the compound shown in Formula 9 to obtain the compound shown in Formula 10b; the compound shown in Formula 10b is subjected to a second deesterification reduction to obtain the chiral porphyrin ligand shown in Formula 1c.

[0041] The compounds used in the above preparation method are as follows:

[0042]

[0043] In some embodiments, in the preparation method of the chiral porphyrin ligand shown in Formula 1a, the first chemical reaction is a condensation oxidation reaction, in which an aldehyde and a dipyrrolidine are condensed into a ring and then oxidized to obtain the corresponding brominated porphyrin ligand. Specifically, the first chemical reaction is carried out under the conditions of a boron-based catalyst and a benzoquinone oxidant, wherein the boron-based catalyst can be a boron trifluoride diethyl ether catalyst, and the benzoquinone oxidant can be a 2,3-dichloro-5,6-dicyano-p-benzoquinone oxidant. Under the above conditions, the first chemical reaction can be carried out better, thereby enabling the compound shown in Formula 2 to react efficiently with the compound shown in Formula 3 to generate the compound shown in Formula 4. The second chemical reaction is a catalytic coupling reaction, in which a chiral amide is attached to a porphyrin ligand to obtain the corresponding chiral porphyrin ligand. Specifically, the second chemical reaction is carried out under the conditions of a mixed catalyst containing a palladium catalyst, a phosphine ligand, and a cesium catalyst, thereby enabling the compound shown in Formula 4 to react efficiently with the compound shown in Formula 5 to generate the chiral porphyrin ligand shown in Formula 1a. The palladium catalyst can be palladium acetate, the phosphine ligand can be 4,5-bis(diphenylphosphine-9,9-dimethyloxanthracene), and the cesium catalyst can be cesium carbonate. The molar ratio of the three can be 1:1.5-2.5:30-50. Such a mixed catalyst has better catalytic effect.

[0044] Specifically, the preparation method of the chiral porphyrin ligand shown in Formula 1a above can be achieved by using bromobenzaldehyde and pyrrole to prepare the corresponding dipyrrolidine raw material shown in Formula 3; then, the condensation of the aldehyde and dipyrrolidine in the compound shown in Formula 2 is catalyzed by Lewis acid boron trifluoride diethyl ether to form a ring, followed by oxidation to obtain the corresponding bromoporphyrin ligand shown in Formula 4. A palladium-catalyzed coupling reaction is then used to attach the chiral amide to the porphyrin ligand to obtain the corresponding chiral porphyrin ligand shown in Formula 1a. Subsequently, a metallization reaction can be performed to prepare the final chiral metalloporphyrin complex. The synthesis of the compound shown in Formula 2, i.e., the chiral C2-symmetric aldehyde, is described in reference [RL Halterman, S.-T. Jan, HL Nimmons, DJ Standlee, MA Khan, Tetrahedron 1997, 53, 11257-11276], and the synthetic route is as follows:

[0045]

[0046] In some embodiments, in the method for preparing the chiral porphyrin ligand shown in Formula 1b, the third chemical reaction is carried out under ammonium alkylate conditions, such as ammonium acetate; the fourth chemical reaction is carried out under azabicyclic catalyst conditions, such as 1,8-diazabicyclic undecane-7-ene (DBU) catalyst; the first deesterification reduction is carried out under metal hydride reducing agent conditions, such as lithium aluminum hydride reducing agent, under which deesterification reduction can lead to cyclization; finally, the fifth chemical reaction, like the second chemical reaction, is a catalytic coupling reaction, which can be carried out under mixed catalyst conditions containing palladium catalyst, phosphine ligand and cesium catalyst, specifically the same mixed catalyst as the second chemical reaction in the preparation of the chiral porphyrin ligand shown in Formula 1a.

[0047] In some embodiments, in the method for preparing the chiral porphyrin ligand shown in Formula 1c, the sixth chemical reaction is carried out under ammonium alkylate conditions, such as ammonium acetate; the seventh chemical reaction is carried out under a nitrogen-bicyclic catalyst conditions, such as 1,8-diazabicycloundec-7-ene (DBU) catalyst; and the second deesterification reduction is carried out under metal hydride reducing agent conditions, such as lithium aluminum hydride reducing agent, which can condense into a ring after deesterification reduction under the metal hydride catalyst conditions, thereby forming the chiral porphyrin ligand shown in Formula 1c.

[0048] Specifically, the chiral porphyrin ligand shown in Formula 1a above is a meso-substituted chiral porphyrin, and the chiral porphyrin ligands shown in Formulas 1b and 1c above are β-substituted chiral porphyrins.

[0049] The third aspect of this application provides a chiral metalloporphyrin complex, comprising a chiral porphyrin ligand containing a metal ion and coordinated to the metal ion, and / or a chiral porphyrin ligand prepared by the above-described preparation method, namely the chiral porphyrin ligands shown in 1a to 1c.

[0050] The aforementioned chiral metalloporphyrin complexes can be prepared by metallization reactions using the chiral porphyrin ligands shown in 1a-1c. The metal ion in the chiral metalloporphyrin complex is selected from any one of iron, cobalt, and ruthenium ions, i.e., a chiral iron porphyrin complex, a chiral cobalt porphyrin complex, or a chiral ruthenium cobalt porphyrin complex.

[0051] The application of the chiral metal porphyrin complex provided in the fourth aspect of this application is based on the fact that the chiral metal porphyrin complex can stably and efficiently catalyze asymmetric organic reactions and can be used as a catalyst for catalyzing C(sp3)-H amination reactions.

[0052] The following description is based on specific embodiments.

[0053] Example 1

[0054] (1)Br-porphyrin synthesis

[0055] 380 mg (1.0 mmol) of 5-(2,6-dibromo)phenyldipyrrolidine and 218 mg (1.0 mmol) of the compound shown in Formula 2 (+) were added to a 250 mL round-bottom flask. 150 mL of chloroform was used as the solvent, and the mixture was stirred under argon atmosphere for 10 min to ensure homogeneity. 100 μL of boron trifluoride diethyl ether solution was added as a catalyst using a microsyringe, and the mixture was stirred at room temperature (25 °C) for 3 h. Then, 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) (273 mg, 1.2 mmol) was added, and the reaction was continued for 0.5 h. 500 μL of triethylamine was then added for neutralization, producing a large amount of white fumes. After the fumes dissipated, the reaction solution was subjected to silica gel column chromatography (100–200 mesh silica gel) with dichloromethane (DCM) as the eluent. DDQ was removed by filtration, and the porphyrin red solution band was collected and evaporated to dryness to obtain the crude product. The crude product was purified by silica gel column chromatography (300-400 mesh) using DCM as the eluent to obtain a purple solid. Recrystallization from a mixed solution of DCM and hexane yielded purple crystals in 65% yield.

[0056]

[0057] (+)-Br-porphyrin: 1H NMR(500MHz,Chloroform-d)δ8.75(s,4H),8.62(s,4H),8.03(d,J=8.1Hz,4H),7.52(t,J=8.2Hz,2H),7.40(s,2H),3.59(s, 4H), 2.78 (s, 4H), 2.04 (d, J = 8.0Hz, 4H), 1.88 (d, J = 11.7Hz, 4H), 1.37 (dt, J = 29.1, 9.8Hz, 12H), 1.02 (s, 4H), -2.47 (s, 2H). 13 C NMR(126MHz,Chloroform-d)δ148.07,144.10,143.37,131.47,131.03,128.58,128.0 8,117.91,117.14,113.81,50.15,49.38,44.35,42.38,27.53,26.78.ESIHR-MS[M+H] + :calc.C 64 H 51 N4Br41191.08417found 1191.08398.

[0058] The synthesis method of (-)-Br-porphyrin is the same as that of (+)-Br-porphyrin, except that the compound shown in (+)-Formula 2 is replaced by the compound shown in (-)-Formula 2.

[0059] (-)-Br-porphyrin: 1 H NMR(500MHz,Chloroform-d)δ8.75(d,J=4.7Hz,4H),8.62(d,J=4.7Hz,4H),8.03(d,J=8.2Hz,4H),7.52(t,J=8.2Hz,2H),7.40(s,2H),3.58(d,J=3.7Hz, 4H),2.78(s,4H),2.04(d,J=7.9Hz,4H),1.87(td,J=11.6,10.5,5.2Hz,4H) ,1.35(dq,J=36.2,16.3,12.3Hz,12H),1.02(d,J=9.3Hz,4H),-2.47(s,2H). 13C NMR(126MHz,Chloroform-d)δ148.07,144.09,143.36,131.47,131.03,128.70,128. 58,128.44,128.08,117.90,117.13,113.81,49.38,44.35,42.37,27.52,26.78.ESI HR-MS[M+H] + :calc.C 64 H 51 N4Br4 1191.08417found 1191.08472.

[0060] (2) Synthesis of chiral porphyrin ligand CMC-porphyrin

[0061] (+)-Br-porphyrin (238 mg, 0.20 mmol), (S)-(+)-2,2-dimethylcyclopropaneformamide (i.e., the compound shown in Formula 5, where R1 and R2 are methyl groups) (361 mg, 3.2 mmol), palladium acetate (18 mg, 0.08 mmol), 4,5-bis(diphenylphosphine-9,9-dimethyloxanthracene) (93 mg, 0.16 mmol), and cesium carbonate (1.04 g, 3.2 mmol) were dissolved in 8 mL of ultra-dry tetrahydrofuran (THF) solvent and reacted under an argon atmosphere for 60 h. After cooling, the reaction solution was subjected to silica gel column chromatography (100–200 mesh silica gel) with ethyl acetate as eluent. The red fluorescent band was collected, and the crude product was obtained by rotary evaporation. The crude product was purified by silica gel column chromatography using 300-400 mesh. The main red fluorescent band was collected using ethyl acetate / petroleum ether (1 / 4) as the eluent. After evaporation, a purple solid was obtained with a yield of 67%.

[0062]

[0063] (+)-cmc-porphyrin: 1 H NMR(500MHz,Chloroform-d)δ8.91(d,J=10.9Hz,8H),8.50(s,3H),7.85(t,J=8.4Hz, 2H),7.47(d,J=3.3Hz,2H),6.63(s,4H),3.66(d,J=3.9Hz,4H),2.74(s,4H),2.12(d, J=8.3Hz,4H),1.91(qd,J=9.1,8.0,4.0Hz,4H),1.49–1.37(m,9H),1.30(d,J=13.5Hz ,4H),0.89(d,J=6.5Hz,17H),0.72(s,3H),0.21(s,11H),0.09(s,9H),-2.46(s,2H).13 C NMR (126MHz, Chloroform-d) δ169.70,169.68,148.17,144.35,139.25,130.45,127.11,118.66,117.33,114. 72,108.30,49.32,44.28,42.40,29.09,29.07,27.36,26.88,26.44,22.32,20.40,18.31.HR-MS(ESI):[M+H] + calc.C 88 H 91 O4N8 1323.71578found1323.71313.

[0064] The synthesis method of (-)-cmc-porphyrin is the same as that of (+)-cmc-porphyrin, except that (-)-Br-porphyrin is used instead of (+)-Br-porphyrin.

[0065] (-)-cmc-porphyrin: 1 H NMR (500MHz, Chloroform-d) δ8.91 (s, 8H), 8.49 (s, 3H), 7.84 (t, J = 8.5Hz, 2H), 7.46 (s, 2H), 6. 60(s,4H),3.64(d,J=3.7Hz,4H),2.69(s,4H),2.05(d,J=8.2Hz,4H),1.92(tt,J=11.1,8.7,4. 3Hz,4H),1.43(dd,J=14.8,8.8Hz,9H),1.35–1.24(m,7H),1.03(d,J=10.3Hz,4H),0.91(s,12H ),0.90–0.86(m,3H),0.71(s,3H),0.23(s,11H),0.08(d,J=6.9Hz,4H),-2.48(d,J=8.2Hz,2H). 13 C NMR(126MHz,Chloroform-d)δ169.64,148.14,147.84,144.35,139.43,139.22,130.41,127.12,118.55,117.42,114.59,108.32,4 9.40,44.25,42.43,42.37,31.62,28.95,27.35,26.88,26.68,26.43,26.36,22.69,22.34,20.49,18.30,14.17.HR-MS(ESI):[M+H]+ calc.C 88 H 91 O4N81323.71578found1323.71423;[M+2H] 2+ calc.662.36153found 662.36267.

[0066] (3) Synthesis of cmc-porphyrin-FeCl

[0067] In a 50 mL round-bottom flask, (+)-cmc-porphyrin (128 mg, 0.1 mmol), 2,6-dimethylpyridine (40 μL), and FeCl2 (127 mg, 0.5 mmol) were added, followed by 15 mL of ultradry N,N-dimethylformamide (DMF). The mixture was refluxed for 2 h under an argon atmosphere. The reaction solution was cooled to room temperature and washed with dilute hydrochloric acid and brine, respectively. The organic phase was collected and evaporated under vacuum to obtain a solid crude product. The crude product was purified by column chromatography using a 300-400 mesh silica gel column, eluting with ethyl acetate / petroleum ether (1 / 4–1 / 3) as the eluent. The target band was collected to obtain a chiral iron porphyrin complex in 85% yield.

[0068]

[0069] The synthesis method of (-)-cmc-porphyrin-FeCl is the same as that of (+)-cmc-porphyrin-FeCl, except that (-)-cmc-porphyrin is used instead of (+)-cmc-porphyrin.

[0070] (4) Synthesis of cmc-porphyrin-Co

[0071] (+)-cmc-porphyrin (128 mg, 0.1 mmol) and CoCl2 (130 mg, 1.0 mmol) were added to a 50 mL round-bottom flask, followed by 20 mL of ultradry THF. The mixture was refluxed for 3 h under an argon atmosphere. The reaction solution was cooled to room temperature and extracted with ethyl acetate, washed three times with water, and the organic phase was collected and evaporated under vacuum to obtain a crude solid product. The crude product was purified by column chromatography using a 300-400 mesh silica gel column, eluting with ethyl acetate / petroleum ether (1 / 4 to 1 / 3) as the eluent. The target band was collected to obtain a chiral cobalt porphyrin complex in 90% yield.

[0072]

[0073] The synthesis method of (-)-cmc-porphyrin-Co is the same as that of (+)-cmc-porphyrin-Co, except that (-)-cmc-porphyrin is used instead of (+)-cmc-porphyrin.

[0074] (4) Synthesis of cmc-porphyrin-RuCO

[0075] Take (+)-cmc-porphyrin (132 mg, 0.1 mmol) and Ru3(CO) 12 (180 mg, 0.28 mmol) was dissolved in 20 mL of acetic acid, and the mixture was heated under reflux and stirred for 24 h under an argon atmosphere. The reaction solution was cooled to room temperature and evaporated under vacuum to obtain a crude red solid product. The crude product was purified by column chromatography using a 300-400 mesh silica gel column, eluted with ethyl acetate / petroleum ether (1 / 4 to 1 / 3) as the eluent, and the target band was collected to obtain a chiral ruthenium porphyrin complex in 30% yield.

[0076]

[0077] The synthesis method of (-)-cmc-porphyrin-RuCO is the same as that of (+)-cmc-porphyrin-RuCO, except that (-)-cmc-porphyrin is used to replace (+)-cmc-porphyrin.

[0078] Example 2

[0079] (1) Synthesis of chiral porphyrin ligands β-D4-porphyrin and β-chiral-porphyrin

[0080] An equimolar amount of the compound shown in Formula 6 (i.e., 2,6-dibromobenzaldehyde) or (+)-the compound shown in Formula 2 (0.01 mol) and ammonium acetate were heated under reflux for 12 h in 20 mL of nitrobenzene solution. After cooling, the solvent was removed. The solid dissolved in dichloromethane and washed three times with water. The organic phase was collected, evaporated to dryness to obtain a crude product, and then recrystallized in a solution of dichloromethane and n-hexane to obtain the target product, i.e., the compound shown in Formula 8a or Formula 8b (where X is methyl).

[0081]

[0082] 1 H NMR (500MHz, Chloroform-d) δ7.79 (d, J = 6.0 Hz, 1H), 7.61 (dt, J = 8.0, 1.6 Hz, 2H), 7.13 (t, J = 8.1 Hz, 1H), 2.09 (dd, J = 3.8, 1.8 Hz, 3H). 13 C NMR (126MHz, Chloroform-d) δ150.86,134.13,132.15,132.04,131.25,131.23,123.39,14.27.

[0083]

[0084] 1 H NMR(500MHz,Chloroform-d)δ8.19(s,1H),7.01(s,1H),3.36–3.31(m,2H),3.27–3.22(m,2H),2.20(d,J=1.0Hz,3H),1.91–1.79( m,4H),1.70(dq,J=8.5,2.1Hz,2H),1.48(dt,J=8.6,1.5Hz,2H),1.10(ddd,J=9.1,7.5,2.5Hz,2H),0.98(tt,J=10.5,2.6Hz,2H). 13 C NMR (126MHz, Chloroform-d) δ148.40,145.86,143.63,132.30,118.92,115.03,48.83,43.92,42.33,27.04,26.62,14.35.

[0085] The target product (10 mmol) and the compound shown in Formula 9, ethyl isocyanate (10 mmol), were dissolved in 10 mL of tetrahydrofuran solvent and cooled to 0 °C. Then, 10 mmol of 1,8-diazabicycloundec-7-ene (DBU) was added dropwise. The reaction system was then brought to room temperature and stirred for 16 h. After the reaction was complete, 10% HCl and ethyl acetate were added, followed by extraction with ethyl acetate and washing with 10% HCl and saturated brine. The organic phase was collected, dried over MgSO4, filtered, and evaporated to dryness. The purified phase was then separated and purified by silica gel column chromatography (ethyl acetate: petroleum ether = 5:95) to give the compound shown in Formula 10a or Formula 10b (X is methyl).

[0086]

[0087] 1 H NMR(500MHz,Chloroform-d)δ9.23(s,1H),7.59(s,2H),7.04(d,J=8.0Hz,1H),6 .85(d,J=3.0Hz,1H),4.10(q,J=7.1Hz,2H),1.89(s,3H),1.01(t,J=6.9Hz,3H). 13CNMR(126MHz,Chloroform-d)δ160.81,137.95,137.64,132.47,131.19,131.09,129.73,129.50,129.40,125.75,125.68,120.49,120.38,120.33,120.15,119.70,119.31,67.34,60.04,21.59,13.85,10.21.HR-MS(ESI):cal.[M+H] + C 14 H 14 Br2NO2 385.9386found385.9382.

[0088]

[0089] 1 H NMR(500MHz,Chloroform-d)δ9.13(s,1H),6.93(s,1H),6.83(d,J=2.7Hz,1H),4.08(dq,J=10.8,7.1Hz,1H),3.98(dq,J=10.7,7.1Hz,1H),3.31(ddd,J=9.1,3.6,1.6Hz,2H),3.07–3.02(m,1H),3.00–2.95(m,1H),1.87–1.76(m,5H),1.74–1.58(m,5H),1.46–1.35(m,3H),1.16(dddd,J=11.1,9.0,3.9,2.2Hz,1H),1.05(dddd,J=11.2,9.0,4.0,2.2Hz,1H),0.98–0.83(m,6H). 13 C NMR(126MHz,Chloroform-d)δ161.94,145.03,144.41,144.14,143.60,128.34,121.41,120.80,120.31,119.41,112.20,59.56,49.07,48.67,44.32,44.24,42.19,42.03,27.57,27.30,26.88,26.39,14.01,10.51.HR-MS ESI[M+H] + cal.C 24 H 28 NO2362.2115found 362.2110.

[0090] The compound of formula 10a or 10b (X being methyl) (3.2 mmol) and LiAlH4 (8 mmol) were dissolved in 30 mL of tetrahydrofuran (THF) and reacted at 0 °C for 2 h. The reaction system was quenched with ethyl acetate and a small amount of water, stirred for 20 min, filtered, and evaporated to dryness to obtain a solid which was directly dissolved in 160 mL of acetic acid and then heated under reflux for 3 h. After cooling to room temperature, the solvent was removed, and the compound of formula 11 (X being methyl) and the chiral porphyrin ligand β-D4-porphyrin were purified by silica gel column chromatography.

[0091]

[0092] 1 H NMR (500MHz, Chloroform-d) δ9.68 (s, 4H), 8.02 (d, J = 8.1Hz, 8H), 7.46 (t, J = 8.2Hz, 4H), 3.33 (s, 12H), -3.22 (s, 2H). 13 C NMR(126MHz,Chloroform-d)δ137.94,132.12,130.99,127.15,99.08,12.40.ESI-MS:[M+H]C 48 H 31 Br8N4 calc.1294.60found 1294.78.

[0093]

[0094] β-D4-porphyrin: 1 H NMR(500MHz,Chloroform-d)δ9.98(s,4H),7.37(s,4H),3.66(d,J=3.7Hz,4H),3.60(d,J=3.6Hz,4H),3.4 8(d,J=3.8Hz,4H),3.44(s,12H),3.37(d,J=3.7Hz,4H),2.32(d,J=7.9Hz,4H),2.11–2.04(m,5H),1.93(d td,J=18.6,10.4,5.4Hz,8H),1.69–1.58(m,8H),1.55(d,J=8.0Hz,4H),1.45–1.36(m,8H),1.31(d,J=13. 1Hz, 4H), 1.25–1.17 (m, 4H), 1.09 (td, J=10.6, 3.8Hz, 4H), 0.93 (tq, J=8.5, 4.6, 3.6Hz, 2H), -3.28 (s, 2H). 13C NMR(126MHz,Chloroform-d)δ146.50,146.40,145.50,145.32,121.83,113.88,99 .37,49.58,49.04,44.77,44.52,42.97,42.68,27.56,27.50,27.14,12.61.HR-MS ESI[M+H] + cal.C 88 H 87 N4 1199.6925found 1199.6904.

[0095] The compound shown in Formula 11 (X being methyl) (159 mg, 0.1 mmol), (S)-(+)-2,2-dimethylcyclopropaneformamide (724 mg, 6.4 mmol), palladium acetate (9 mg, 0.04 mmol), 4,5-bis(diphenylphosphine-9,9-dimethyloxanthracene) (46 mg, 0.08 mmol), and cesium carbonate (0.52 g, 1.6 mmol) were dissolved in 4 mL of ultra-dry THF solvent and reacted under an argon atmosphere for 60 h. After cooling, the reaction solution was subjected to silica gel column chromatography (100–200 mesh silica gel) with ethyl acetate as the eluent. The red fluorescent band was collected, and the crude product was obtained by rotary evaporation. The crude product was purified by separation and purification using a 300–400 mesh silica gel column with ethyl acetate / petroleum ether (1 / 1) as the eluent. The main red fluorescent band was collected, and the crude product was obtained by rotary evaporation to obtain purple β-chiral-porphyrin.

[0096]

[0097] β-chiral-porphyrin: 1 H NMR(500MHz,Chloroform-d)δ10.02(s,4H),8.97–8.04(m,8H),7.83(t,J=8.4Hz,4H),7.24(s,4H),7.03(s,4H),3.51(s,12H),1.14(s,13 H),1.00(d,J=4.8Hz,5H),0.79(d,J=25.1Hz,17H),0.55(d,J=18.2Hz,18H),0.29(s,11H),0.17–0.01(m,4H),-0.10(s,4H),-3.09(s,2H). 13C NMR(126MHz,Chloroform-d)δ170.04,138.21,137.92,133.72,130.84,119.03,100.22,29 .49,29.19,26.70,26.51,22.97,21.40,20.58,18.34,18.17,14.24,12.65.ESI-MS:[M+H]C 96 H 111 N 12 O8 calc.1559.86found 1559.92,[M+Na]C 96 H 110 N 12 O8Na calc.1581.85found 1581.81.

[0098] (2) β-D 4 Synthesis of chiral metalloporphyrin complexes of β-porphyrin and β-chiral-porphyrin

[0099] The synthesis method of the metal complexes of β-D4-porphyrin and β-chiral-porphyrin is the same as that in Example 1.

[0100] Example 3

[0101] (1) Chiral metalloporphyrin complexes as catalysts for the catalysis of C(sp) 3 )-H amination reaction [a] The different catalysts and reaction conditions are shown in Table 1 below:

[0102]

[0103] Table 1

[0104]

[0105] [a]Catalyst (2mol%), azide (0.2mmol), Boc2O (0.24mmol) and solvent (2mL) wasirradiated with 410nm LED under Ar; [b] Isolate yield; [c] Determined by HPLC; [d] 2.0eq.Boc2O; [e] Dark condition.

[0106] (2) Substrate expansion

[0107]

[0108]

[0109] (3) Substrate expansion [a]

[0110]

[0111]

[0112] [a]Azide(0.2 mmol),(S,R)-cmcporFeCl(2 mol%)and toluene(2 mL)wasirradiated with 410 nm blue LED under argon atmosphere at 40℃; Isolateyields; ee values ​​were determined by HPLC.[b]at 25℃.

[0113] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. A chiral metalloporphyrin complex, characterized in that, It includes a metal ion and a chiral porphyrin ligand coordinated to the metal ion, the general molecular structure of which is shown in Formula 1: Formula 1; in, R1 and R2 are the same or different alkyl groups with 1 to 10 carbon atoms; The metal ions are selected from iron ions.

2. The chiral metalloporphyrin complex as described in claim 1, characterized in that, R1 and R2 are methyl groups.

3. The method for preparing the chiral metalloporphyrin complex according to any one of claims 1-2, characterized in that, Includes the following steps: The compound shown in Formula 2 is subjected to a first chemical reaction with the compound shown in Formula 3 to obtain the compound shown in Formula 4; the compound shown in Formula 4 is subjected to a second chemical reaction with the compound shown in Formula 5 to obtain the chiral porphyrin ligand. 。 4. The method for preparing the chiral metalloporphyrin complex according to claim 3, characterized in that, The first chemical reaction is carried out under conditions of a boron-based catalyst and a benzoquinone oxidant; and / or, The second chemical reaction is carried out under mixed catalyst conditions containing palladium catalyst, phosphine ligand and cesium catalyst.

5. The chiral metalloporphyrin complex as described in any one of claims 1-2 is used as a catalyst in the catalytic C(sp3)-H amination reaction.

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