Process for the preparation of planar chiral indenyl metal complexes having a benzazulene skeleton, synthetic intermediates and catalytic applications

Abstract

The application belongs to the technical field of asymmetric catalytic synthesis, and particularly relates to a preparation method of a planar chiral indene metal complex with a benzazulene skeleton, a synthesis intermediate and catalytic application. The application provides a key intermediate for preparing the planar chiral indene metal complex, i.e. a chiral indenone in (R) configuration and (S) configuration, and a chiral indene ligand without a coordinating side arm prepared based on the chiral indenone. The chiral indene ligand of the application is strong in modification, easy to complex with a transition metal compound to obtain a single planar chiral indene metal complex. The planar chiral indene metal complex can be applied to various asymmetric carbon hydrogen activation reactions as a catalyst, and the chiral indene metal complex does not need to be separated into stereoisomers in a synthesis process, so that the synthesis difficulty and costs in various aspects are greatly reduced.

Description

Technical Field

[0001] This application belongs to the field of asymmetric catalytic synthesis technology, and particularly relates to the preparation method, synthetic intermediates and catalytic applications of planar chiral indene metal complexes with a benzene-indene skeleton. Background Technology

[0002] Asymmetric catalysis is an important method for synthesizing chiral organic molecules. Chiral indene metal catalysts, as a class of highly reactive and functionally compatible catalysts, have been widely used in asymmetric catalytic synthesis. Among them, chiral indene ligands without coordination arms have great application value in asymmetric catalysis. Chiral indene ligands without coordination arms refer to those without coordinating chiral substituents on the indene ring, and the chiral skeleton on the indene ring can provide chiral control. Previous literature mainly reported chiral indene ligands based on the chiral menthol skeleton, which can complex with zirconium, yttrium, cobalt, and rhodium to form metal catalysts. They have shown good catalytic effects in asymmetric alkylalumination reactions, asymmetric hydroamination reactions of olefins, and asymmetric hydrogenation reactions. In 2023, the Loginov research group successfully synthesized a chiral indene ligand without coordination arms from the natural product α-pinene. It exhibits stereospecificity when coordinated with rhodium, without the need for chiral separation, but the drawback is that this structure is difficult to modify. This catalyst has been applied in the asymmetric hydrocarbon-activated synthesis of chiral hydrogenated isoquinolinones. In recent years, progress has also been made in preparing planar chiral indene metal catalysts from achiral, non-coordinating indene ligands. In 2020, Baik and Blakey's group successfully resolved racemic rhodium complexes containing prochiral indene ligands using chiral preparative liquid chromatography, obtaining optically pure chiral indene-rhodium catalysts. These catalysts have been successfully applied to the asymmetric amidation of allyl compounds and the asymmetric nitrogen heterocyclization of unactivated alkenes.

[0003] Because most indene ligands lack stereoselectivity when complexing with metals, they produce stereoisomers, requiring separation and purification via chiral preparative liquid chromatography or recrystallization. This process is difficult and costly, hindering the synthesis of optically pure indene metal complexes. Secondly, existing chiral indene ligands without coordination arms have poor modifiability, making them difficult to widely apply and achieve excellent catalytic results in asymmetric catalysis. Furthermore, the variety of existing chiral indene ligands without coordination arms is extremely limited, indicating a severe shortage of such ligands. Summary of the Invention

[0004] Based on this, this application develops a chiral indene ligand with a non-coordination side arm that is easily modified in structure and can stereospecifically complex metals, as well as a key intermediate (chiral indene ketone) for preparing this chiral indene ligand. Furthermore, the planar chiral indene metal complex obtained based on this chiral indene ligand exhibits catalytic performance in asymmetric hydrocarbon activation reactions, with excellent yield and enantioselectivity.

[0005] The first aspect of this application provides chiral indanones with (R)-configuration and (S)-configuration, wherein the (R)-configuration chiral indanone has a chemical structure as shown in Formula (1) and the (S)-configuration chiral indanone has a chemical structure as shown in Formula (2):

[0006]

[0007] A second aspect of this application discloses a method for synthesizing chiral indanone, the method comprising:

[0008] Step 1: A chiral cyclopropionic acid consisting of (R)-configuration, (S)-configuration, or any ratio of (R)-configuration and (S)-configuration is condensed and reduced with cyclo()isopropyl malonate to generate cyclopropionic acid consisting of (R)-configuration, (S)-configuration, or any ratio of (R)-configuration and (S)-configuration.

[0009] The (R)-configuration chiral cyclopropionic acid has the chemical structure shown in formula (3), the (S)-configuration chiral cyclopropionic acid has the chemical structure shown in formula (4), the (R)-configuration cyclopropionic acid has the chemical structure shown in formula (5), and the (S)-configuration cyclopropionic acid has the chemical structure shown in formula (6).

[0010]

[0011] Step 2: React the (S)-configuration, (R)-configuration, or any ratio of (S)-configuration and (R)-configuration of cyclopropionic acid in methanesulfonic acid to generate (R)-configuration, (S)-configuration, or any ratio of (R)-configuration and (S)-configuration of chiral indanone, respectively.

[0012] The (R)-configuration chiral indanone has the chemical structure shown in Formula (1), and the (S)-configuration chiral indanone has the chemical structure shown in Formula (2):

[0013]

[0014] Specifically, the synthetic methods for chiral indanone include: ① chiral cyclic aldehydes of (R)-configuration, (S)-configuration, or any ratio of (R)-configuration and (S)-configuration, and formate salts of cyclo(isopropyl)malonic acid or amines (structural formula R4N). + HCO2 -① A mixture of alkyl (or hydrogen) or amine and formic acid is heated in a solvent to generate the corresponding (R)-configuration, (S)-configuration, or cyclopropionic acid composed of any ratio of (R)-configuration and (S)-configuration. The solvent for this reaction can be conventional solvents such as DMF, DMSO, NMP, N,N-dimethylacetamide, acetone, acetonitrile, pyridine, ethyl acetate, N,N-diethylformamide, toluene, dioxane, etc. Preferably, the solvent is DMF; ② The cyclopropionic acid composed of (S)-configuration, (R)-configuration, or cyclopropionic acid composed of any ratio of (S)-configuration and (R)-configuration is reacted in methanesulfonic acid to generate the corresponding (R)-configuration, (S)-configuration, or chiral indanone composed of any ratio of (R)-configuration and (S)-configuration.

[0015] A third aspect of this application provides chiral indene ligands of (R)-configuration, (S)-configuration, or any ratio of (R)-configuration and (S)-configuration, wherein the (R)-configuration chiral indene ligand has a chemical structure as shown in Formula (7), and the (S)-configuration chiral indene ligand has a chemical structure as shown in Formula (8):

[0016]

[0017] In equations (7) and (8), R 1 Selected from alkyl, heteroalkyl, heteroaryl, or aryl; R 2 Selected from H, alkyl, heteroalkyl, heteroaryl, or aryl. Preferably, the R... 1 Selected from Me, Et, i Pr、 i Bu、 t Bu, Cy, Ph, 2-Me-C6H4, 2-OMe-C6H4, 2-OEt-C6H4, 2-O i Pr-C6H4, 2,6-di-OMe-C6H3 or 3,5-di- t Bu-C6H3; the R 2 Selected from H, Me, Et, n Pr or Ph.

[0018] The fourth aspect of this application discloses a method for synthesizing the chiral indene ligand, the method comprising: reacting the chiral indene ketone with a nucleophilic reagent, and then dehydrating it to prepare the chiral indene ligand.

[0019] In some embodiments, the nucleophile is selected from Grignard reagents RMgX, organolithium reagents RLi, organocopper reagents R2CuLi, organozinc reagents R2Zn, or organoaluminum reagents R3Al. Preferably, the nucleophile is MeMgBr, EtMgBr, etc. i PrMgBr, iBuLi、 t BuMgBr, CyMgBr, PhMgBr, 2-Me-C6H4Li, 2-OMe-C6H4Li, 2-OEt-C6H4Li, 2-O i Pr-C6H4Li, 2,6-di-OMe-C6H3Li or 3,5-di- t Bu-C6H3Li.

[0020] Specifically, the method for synthesizing the chiral indene ligand further includes: reacting the chiral indene ketone, an additive, and a nucleophilic reagent, followed by dehydration to prepare the chiral indene ligand; the additive is a lanthanide (III) salt, such as CeCl3 or LnCl3·2LiCl (Ln = La, Ce, Nd), preferably, the additive is LaCl3·2LiCl, and the additive can improve the reaction yield.

[0021] The fifth aspect of this application provides planar chiral indene metal complexes with a benzene-indene skeleton, comprising (R)-configuration, (S)-configuration, or any ratio of (R)-configuration and (S)-configuration, wherein the (R)-configuration planar chiral indene metal complex has a chemical structure as shown in Formula (9), and the (S)-configuration planar chiral indene metal complex has a chemical structure as shown in Formula (10):

[0022]

[0023] In equations (9) and (10), R 1 Selected from alkyl, heteroalkyl, heteroaryl, or aryl; R 2 The ligand is selected from H, alkyl, heteroalkyl, heteroaryl, or aryl; M is selected from rhodium, iridium, iron, cobalt, ruthenium, scandium, yttrium, or lanthanum; L is selected from monoolefins, dienes, aromatics, halide anions, acid anions, cyclopentadienyl anions, indene anions, o-aminobenzyl anions, carbon monoxide, phosphine ligands, nitrogen-containing aromatics, amines, or sulfur compounds; n represents the number of ligands, and n is an integer from 0 to 5; preferably, R1 is selected from Me, Et, i Pr、 i Bu、 t Bu, Cy, Ph, 2-Me-C6H4, 2-OMe-C6H4, 2-OEt-C6H4, 2-O i Pr-C6H4, 2,6-di-OMe-C6H3 or 3,5-di- t Bu-C6H3; the R2 is selected from H, Me, Et, n Pr or Ph.

[0024] The sixth aspect of this application discloses a method for synthesizing the planar chiral indene metal complex, the method comprising: reacting the chiral indene ligand with a transition metal compound to generate a planar chiral indene metal complex, wherein L in the planar chiral indene metal complex is selected from monoene or diene ligands, aromatic hydrocarbons, halide anions, acid radical anions, cyclopentadienide anions, indene anions, o-aminobenzyl anions, carbon monoxide, phosphine ligands, aza-aromatic hydrocarbons, amine compounds, or sulfur compounds, and n represents the number of ligands, where n is an integer from 0 to 5.

[0025] A seventh aspect of this application discloses a method for synthesizing the planar chiral indene metal complex, the method comprising:

[0026] Step a: React the chiral indene ligand with a transition metal compound to generate a first planar chiral indene metal complex, wherein L in the first planar chiral indene metal complex is selected from a monoene or diene ligand;

[0027] Step b: The first planar chiral indene metal complex described in step a is reacted with an oxidant, such as a halogen, hydrogen halide, peroxide, or metal oxidant, to generate a second planar chiral indene metal complex. In the second planar chiral indene metal complex, L represents a halide anion or an acid radical anion, and n represents the number of ligands, which is an integer from 0 to 5. Preferably, the halide anion is selected from chlorine, bromine, or iodine.

[0028] Specifically, the method for synthesizing the planar chiral indene metal complex includes: ① under solvent conditions, a chiral indene ligand, a base reagent, and a transition metal compound are heated to react and generate a first planar chiral indene metal complex, wherein the base reagent is an alkoxide (ROM, where R is an alkyl group and M is an alkali metal ion), an organolithium reagent (RLi), or an organomagnesium reagent (RMgX), preferably, the base reagent is KO. t Bu; the solvent can be a conventional solvent such as anhydrous tetrahydrofuran, anhydrous diethyl ether, dioxane, toluene, etc., preferably, the solvent is tetrahydrofuran; ② under solvent conditions, the first planar chiral indene metal complex is reacted with an oxidant, such as a halogen element (such as elemental iodine, chlorine or elemental bromine), hydrogen halide, peroxide or metal oxidant, to generate a second planar chiral indene metal rhodium complex, preferably, the oxidant is elemental iodine; wherein, the solvent used for this reaction can be a conventional solvent such as anhydrous diethyl ether, tetrahydrofuran, dichloromethane, 1,2-dichloroethane, toluene, etc., preferably, the solvent is anhydrous diethyl ether.

[0029] In some embodiments, the transition metal compound is selected from rhodium compounds, iridium compounds, cobalt compounds, ruthenium compounds, scandium compounds, yttrium compounds, or lanthanum compounds. Preferably, the transition metal compound is a rhodium compound or an iridium compound; more preferably, the transition metal compound is [Rh(COD)Cl]2.

[0030] The eighth aspect of this application discloses the application of the planar chiral indene metal complex or the planar chiral indene metal complex prepared by the synthesis method as a catalyst in catalyzing asymmetric hydrocarbon activation reactions.

[0031] Specifically, the asymmetric hydrocarbon activation reaction can be the reaction of N-BocO-benzamide with norbornene or cyclohexadiene to synthesize chiral dihydroisoquinolinone, and the reaction of benzoic acid with alkynes to synthesize axial chiral isocoumarin.

[0032] This application provides a key intermediate for preparing the planar chiral indene metal complex—chiral indene ketone, a chiral indene ligand without coordination side arms prepared based on the chiral indene ketone, and a planar chiral indene metal complex obtained based on the chiral indene ligand. The chiral indene ligand provided in this application is highly modifiable and easily complexes with transition metal compounds to prepare a single planar chiral indene metal complex. This planar chiral indene metal complex can be used as a catalyst in various asymmetric hydrocarbon activation reactions, and the synthesis of this chiral indene metal complex does not require the separation of stereoisomers, greatly reducing the synthesis difficulty and costs in all aspects. Data from the examples in this application show that the planar chiral indene metal complex can catalyze asymmetric hydrocarbon activation reactions with excellent yields and enantioselectivity. Attached Figure Description

[0033] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the accompanying drawings used in the description of the embodiments or the prior art will be briefly introduced below.

[0034] Figure 1 Synthetic routes for synthesizing (R)-configured planar chiral indene metal complexes (R)-5 and (R)-6 from (S)-configured chiral cycloalkanes (S)-1 as starting material, provided in this application;

[0035] Figure 2 Synthetic routes for planar chiral indene metal complexes (R)-5a and (R)-6a provided for embodiments of this application;

[0036] Figure 3 Synthetic routes for planar chiral indene rhodium complexes (R)-5h and (R)-6h provided for embodiments of this application;

[0037] Figure 4 Synthetic routes for planar chiral indene rhodium complexes (R)-5n and (R)-6n provided for embodiments of this application;

[0038] Figure 5Synthetic route diagram for the synthesis of P1 from A1 and B1 using planar chiral indene rhodium complexes (compounds (R)-6a to (R)-6o) as catalysts, provided for embodiments of this application;

[0039] Figure 6 Synthetic route for synthesizing P2 from A1 and B2 using a planar chiral indene-rhodium complex (compound (R)-6b) as a catalyst, provided in the embodiments of this application;

[0040] Figure 7 Synthetic route for synthesizing P3 from A2 and B3 using a planar chiral indene-rhodium complex (compound (R)-6i) as a catalyst, provided in the embodiments of this application. Detailed Implementation

[0041] This application provides a method for preparing planar chiral indene metal complexes with a benzene-indene skeleton, synthetic intermediates, and catalytic applications, to address the technical deficiency of the extremely limited variety of existing chiral indene ligands without coordinating side arms.

[0042] The technical solutions in the embodiments of this application will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. Based on the embodiments in this application, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of this application.

[0043] In the following examples, all reagents or drugs used are commercially available or self-made.

[0044] Figure 1 The synthetic route for synthesizing a (R)-configuration planar chiral indene metal complex from a (S)-configuration chiral cycloalkane is shown. The synthetic method includes: 1) the chiral cycloalkane ((S)-1) shown in formula (4) reacts with cyclo(isopropyl)malonic acid under the conditions of formic acid, triethylamine and DMF at 120°C to generate cyclopropionic acid ((S)-2) shown in formula (6); 2) the cyclopropionic acid ((S)-2) shown in formula (6) reacts with methanesulfonic acid at 70°C to generate chiral indene ketone ((R)-3a) shown in formula (11). 1) R is H; then, the chiral indanone ((R)-3a) shown in formula (11) reacts with Cu(TFA)·×H2O and K2S2O8 in DMF at 100℃ to generate (R)-3b shown in formula (12), and then (R)-3b shown in formula (12) reacts with hydrogen under palladium on carbon catalysis to generate the chiral indanone ((R)-3c) shown in formula (13); 3) The chiral indanone ((R)-3a) shown in formula (11) or the chiral indanone ((R)-3c) shown in formula (13) reacts with nucleophiles (such as R) respectively. 1 MgBr or R 1Li) undergoes an addition reaction, followed by dehydration with hydrochloric acid to obtain the chiral indene ligand ((R)-4) shown in formula (7). Additives (such as LaCl3·2LiCl) can improve the yield of this step; 4) The chiral indene ligand ((R)-4) shown in formula (7) reacts with a transition metal compound in KO t Bu reacts with anhydrous tetrahydrofuran at 70°C to generate a planar chiral indene metal complex ((R)-5) as shown in formula (14); then, the planar chiral indene metal complex ((R)-5) as shown in formula (14) reacts with a halogen (such as iodine) in anhydrous diethyl ether at room temperature to generate a planar chiral indene metal complex ((R)-6) as shown in formula (15).

[0045]

[0046] Example 1

[0047] This embodiment provides a first type of method for synthesizing planar chiral indene-rhodium metal complexes with a benzoindene skeleton, specifically including:

[0048] like Figure 2 As shown, taking the synthesis of planar chiral indene rhodium complexes (R)-5a and (R)-6a as examples, the synthesis method includes: ① condensation-reduction reaction of chiral cycloalkanol (compound (S)-1) with cycloisopropyl malonate to generate compound (S)-2; ② reaction of compound (S)-2 with methanesulfonic acid to generate chiral indene ketone (R)-3a; ③ reaction of chiral indene ketone (R)-3a with nucleophile MeMgBr (or other nucleophiles for other examples) and acid dehydration to generate chiral indene ligand (R)-4a; ④ reaction of chiral indene ligand (R)-4a with transition metal compound [Rh(COD)Cl]2 to generate metal complex (R)-5a; ⑤ reaction of metal complex (R)-5a with elemental iodine to generate planar chiral indene rhodium complex (R)-6a.

[0049] The specific steps include:

[0050] 1. Synthesis of compound (S)-2: In a dry 100 mL round-bottom flask, chiral cycloalkanol (S)-1 (5 g, 21.1 mmol, 1.0 equiv), cycloisopropyl malonate (3.6 g, 25.3 mmol, 1.2 equiv), formic acid (2.5 mL), triethylamine (3.5 mL), and DMF (20 mL) were added at room temperature. The reaction mixture was stirred in an oil bath at 120 °C for 24 hours. After cooling the reaction mixture to room temperature, water (60 mL) was added, and the mixture was extracted with ethyl acetate (3 × 30 mL). The organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was collected and concentrated using a rotary evaporator. The crude product was purified by silica gel column chromatography (PE / EA = 3:1) to give compound (S)-2. The chemical structural formula of compound (S)-2 is as follows:

[0051]

[0052] Product: Compound (S)-2 is a white solid; 5.3 g; yield 90%. Spec. Rot.: δ=6.71(dd,J=7.9,1.9Hz,1H),6.54(dd,J=7.9,1.9Hz,1H),6.51–6.38(m,4H),6.16(s,1H),3 .43–3.30(m,1H),3.21–2.89(m,7H),2.88–2.79(m,1H),2.71–2.59(m,1H),2.58–2.44(m,2H). 13 C NMR (101MHz, CDCl3): δ=179.3,140.2,139.6,139.5,139.4,137.6,135.1,134.3,133.5 ,133.3,132.2,131.0,128.9,35.4,35.1,34.8,34.3,33.5,29.1.HRMS(ESI)m / z:[M+H] + Calcd for C 19 H 21 O2281.1536; Found281.1543.

[0053] 2. Synthesis of chiral indanone (compound (R)-3a): Compound (S)-2 (1.0 g, 3.5 mmol, 1.0 equiv) and methanesulfonic acid (20 g) were added to a dry 100 mL round-bottom flask at room temperature. The reaction mixture was stirred in a 70 °C oil bath for 12 hours. After cooling the reaction mixture to room temperature, it was poured into ice water (100 mL). Extraction was performed with ethyl acetate (3 × 10 mL). The organic phases were combined, washed with saturated brine (20 mL), dried over anhydrous sodium sulfate, and the filtrate was collected and concentrated using a rotary evaporator. The crude product was purified by silica gel column chromatography (PE / EA = 6:1) to give compound (R)-3a. The chemical structural formula of compound (R)-3a is:

[0054]

[0055] Product: Compound (R)-3a is a white solid; 0.78 g; yield 85%. Spec. Rot.: δ=6.66(d,J=7.5Hz,1H),6.62–6.56(m,3H),6.45(dd,J=7.8,2.0Hz,1H),6.30(dd,J=7.9,2.0Hz,1H),4.25– 4.13(m,1H),3.31–3.18(m,1H),3.17–3.02(m,4H),2.98–2.89(m,1H),2.89–2.69(m,3H),2.61–2.42(m,2H). 13 C NMR (101MHz, CDCl3): δ=207.6,156.4,141.0,140.1,139.1,139.0,138.2,137.3,133.9 ,133.8,133.6,130.2,126.8,36.2,34.0,33.9,31.5,31.4,24.7.HRMS(ESI)m / z:[M+H] + Calcd for C 19 H 19 O 263.1430; Found 263.1436.

[0056] 3. Synthesis of the chiral indene ligand (compound (R)-4a): In a dry 25 mL round-bottom flask, indene ketone (R)-3a (0.3 mmol, 1.0 equiv), THF (2 mL), and LaCl3·2LiCl (0.6 M in THF, 1 mL, 2 equiv) were added at room temperature and under a nitrogen atmosphere, and the mixture was stirred for 1 hour. The reaction solution was cooled to 0 °C, and MeMgBr (3 equiv) was slowly added. The reaction was continued at room temperature for 2 hours. The reaction solution was cooled to 0 °C, and 6 M HCl (3 mL) was slowly added, and the mixture was stirred for 1 hour. The mixture was extracted with ethyl acetate (3 × 3 mL). The organic phases were combined, washed with saturated brine (3 mL), dried over anhydrous sodium sulfate, and the filtrate was collected by filtration. The filtrate was concentrated using a rotary evaporator. The crude product was purified by silica gel column chromatography (eluting with petroleum ether) to give compound (R)-4a. The chemical structure of compound (R)-4a is as follows:

[0057]

[0058] Product: Compound (R)-4a is a colorless liquid; 51 mg; yield 65%. Spec. Rot.: δ=6.58(dd,J=7.8,1.9Hz,1H),6.55–6.49(m,2H),6.43(d,J=7.7Hz,1H),6.33(dd,J=7.8,1.9Hz,1H),6.24(dd,J=7.8,1.9Hz,1H),6 .19–6.14(m,1H),3.72–3.57(m,1H),3.29–3.13(m,2H),3.12–2.96(m,3H),2.97–2.82(m,2H),2.81–2.68(m,2H),2.38–2.29(m,3H). 13 C NMR (101MHz, CDCl3): δ=146.6,145.7,142.2,139.1,138.9,135.0,133.8,133.2,133.1,13 2.5,130.0,129.7,128.2,125.6,37.0,35.6,34.2,33.1,32.2,16.4.HRMS(APCI)m / z:[M+H] + Calcd forC 20 H 21 261.1638; Found 261.1639.

[0059] 4. Synthesis of planar chiral indene-rhodium complex 1—compound (R)-5a: In a dry 25 mL round-bottom flask, under a nitrogen atmosphere and at room temperature, compound (R)-4a (0.25 mmol, 1.0 equiv), [Rh(COD)Cl]2 (74 mg, 0.15 mmol, 0.6 equiv), and KO were added. t After adding Bu (42 mg, 0.375 mmol, 1.5 equiv) and anhydrous tetrahydrofuran (2 mL), the reaction solution was placed in an oil bath at 70 °C and stirred for 20 hours. The reaction solution was cooled to room temperature and concentrated using a rotary evaporator. The crude product was purified by alkaline silica gel column chromatography (5% triethylamine in petroleum ether solution) (eluting with petroleum ether) to give compound (R)-5a. The chemical structural formula of compound (R)-5a is:

[0060]

[0061] Product: Compound (R)-5a is a yellow solid; 75 mg; yield 83%. Spec. Rot.: δ=6.51–6.44(m,2H),6.35(d,J=7.2Hz,1H),6.32(d,J=7.2Hz,1H),6.26(dd,J=7.7, 1.7Hz,1H),6.01(dd,J=7.7,1.7Hz,1H),5.78(t,J=2.3Hz,1H),4.71(d,J=2.8Hz,1H ),3.64–3.55(m,2H),3.43–3.34(m,1H),3.27–3.17(m,2H),3.14–2.95(m,3H),2.94 –2.79(m,3H),2.74–2.63(m,1H),1.99(s,3H),1.88–1.74(m,4H),1.69–1.57(m,4H). 13 C NMR (101MHz, CDCl3): δ = 138.2, 138.1, 131.9, 131.8, 131.6, 131.0, 129.6, 128.1, 127.5, 127.4, 115.9 (d, J = 3.0Hz), 115.4 (d, J = 2.4Hz), 92.9 (d,J=4.7Hz),88.9(d,J=3.8Hz),74.6(d,J=4.3Hz),70.1,70.0,66.8,66.7,36.0,34.6,33.9,33.0,31.6,31.4,13.4.HRMS(APCI)m / z:[M+H] + Calcd forC 28 H 32Rh 471.1554; Found 471.1548.

[0062] 5. Synthesis of planar chiral indene-rhodium complex 2—compound (R)-6a: In a dry 25 mL round-bottom flask, compound (R)-5a (0.25 mmol, 1.0 equiv), iodine (76 mg, 0.3 mmol, 1.2 equiv), and anhydrous diethyl ether (5 mL) were added at room temperature, and the mixture was stirred for 1 hour. The resulting brownish-black precipitate was collected by filtration through a Buchner funnel and washed with diethyl ether (10 mL). The precipitate was dried under vacuum to obtain compound (R)-6a. The chemical structural formula of compound (R)-6a is as follows:

[0063]

[0064] Product: Compound (R)-6a is a brownish-black solid, 59 mg, yield 60%. 1 H NMR(400MHz, DMSO-d6:CDCl3(v / v=1:1)): δ=6.78(d,J=7.3Hz,2H),6.69(d,J=7.3Hz,2H),6.66–6.61(m,4H),6.38–6.24( m,2H),6.18–6.12(m,4H),5.99(d,J=2.8Hz,2H),3.53–3.42(m,2H),3.33–3.02(m,12H),2.98–2.87(m,2H),2.42(s,6H). 13 C NMR (101MHz, DMSO-d6: CDCl3 (v / v=1:1)): δ=139.9,139.1,139.0,138.9,137.3,136.4,133.0,132.5,131.3,130.6,113.1(d,J=3.8H z),111.3(d,J=4.2Hz),97.3(d,J=6.5Hz),91.8(d,J=6.4Hz),73.5(d,J=6.7Hz),35.3,34.3,33.5,33.1,14.1.HRMS(ESI)m / z:[M–I] + Calcd for C 40 H 38 I3Rh21104.8212;Found 110.48221.

[0065] Example 2

[0066] This embodiment prepares a planar chiral indene-rhodium complex similar to that in Example 1. The method includes: using chiral indene ketone (compound (R)-3a) as a starting material to prepare compound (R)-6b (chemical structure shown below), the synthesis method is the same as in Example 1, except that MeMgBr in step (R)-4a) is replaced with EtMgBr (3 equiv). The obtained compound (R)-6b is a brownish-black solid; 79 mg; yield 61%. HRMS (ESI) m / z: [M–I] + Calcd for C 42 H 42 I3Rh21132.8525; Found1132.8536.

[0067]

[0068] Example 3

[0069] This embodiment prepares a planar chiral indene-rhodium complex similar to that in Example 1. The method includes: using chiral indene ketone (compound (R)-3a) as a starting material to prepare compound (R)-6c (chemical structure shown below), the synthesis method is the same as in Example 1, except that MeMgBr in the step of compound (R)-4a is replaced with i PrMgBr (3 equiv) yielded compound (R)-6c as a brownish-black solid; 87 mg; yield 45%. HRMS (ESI) m / z: [M–I] + Calcd for C 44 H 46 I3Rh21160.8838; Found1160.8844.

[0070]

[0071] Example 4

[0072] This embodiment prepares a planar chiral indene-rhodium complex similar to that in Example 1. The method includes: using chiral indene ketone (compound (R)-3a) as a starting material to prepare compound (R)-6d (chemical structure shown below), the synthesis method is the same as in Example 1, except that MeMgBr in the step of compound (R)-4a is replaced with i BuLi (3 equiv) yielded compound (R)-6d as a brownish-black solid; 86 mg; yield 57%. HRMS (ESI) m / z: [M–I] + Calcd for C 46 H 50 I3Rh21188.9151; Found1188.9159.

[0073]

[0074] Example 5

[0075] This embodiment prepares a planar chiral indene-rhodium complex similar to that in Example 1. The method includes: using chiral indene ketone (compound (R)-3a) as a starting material to prepare compound (R)-6e (chemical structure shown below), the synthesis method is the same as in Example 1, except that MeMgBr in the step of compound (R)-4a is replaced with t BuMgBr (3 equiv) yielded a compound (R)-6e as a brownish-black solid; 45 mg; yield 21%. HRMS (ESI) m / z: [M–I] + Calcd for C 46 H 50 I3Rh21188.9151; Found1188.9145.

[0076]

[0077] Example 6

[0078] This embodiment prepares a planar chiral indene-rhodium complex similar to that in Example 1. The method includes: using chiral indene ketone (compound (R)-3a) as a starting material to prepare compound (R)-6f (chemical structure shown below), the synthesis method is the same as in Example 1, except that MeMgBr in step (R)-4a) is replaced with CyMgBr (3 equiv). The obtained compound (R)-6f is a brownish-black solid; 78 mg; yield 70%. HRMS (ESI) m / z: [M–I] + Calcd for C 50 H 54 I3Rh21240.9464; Found1240.9472.

[0079]

[0080] Example 7

[0081] This embodiment prepares a planar chiral indene-rhodium complex similar to that in Example 1. The method includes: using chiral indene ketone (compound (R)-3a) as a starting material to prepare compound (R)-6g (chemical structure shown below), the synthesis method is the same as in Example 1, except that MeMgBr in step (R)-4a) is replaced with PhMgBr (3 equiv). The obtained compound (R)-6g is a brownish-black solid; 78 mg; yield 70%. HRMS (ESI) m / z: [M–I] + Calcd for C 50 H 54I3Rh21240.9464; Found1240.9472.

[0082]

[0083] Example 8

[0084] This embodiment provides a second type of method for synthesizing planar chiral indene-rhodium metal complexes with a benzoindene skeleton, specifically including:

[0085] like Figure 3 As shown, taking the synthesis of planar chiral indene rhodium complexes (R)-5h and (R)-6h as examples, the synthesis method includes: ① reacting chiral indene ketone (R)-3a with the nucleophile 2-methylbenzene lithium (or other nucleophiles for other examples) and adding acid for dehydration to generate chiral indene ligand (R)-4h; ② reacting chiral indene ligand (R)-4h with the transition metal compound [Rh(COD)Cl]2 to generate compound (R)-5h; ③ reacting compound (R)-5h with elemental iodine to generate planar chiral indene rhodium complex (R)-6h.

[0086] The specific steps include:

[0087] 1. Synthesis of compound (R)-4h: In a dry 25 mL round-bottom flask, chiral indanone (R)-3a (0.3 mmol, 1.0 equiv), diethyl ether (2 mL), and LaCl3·2LiCl (0.6 min THF, 1 mL, 2 equiv) prepared in the above example were added under a nitrogen atmosphere at room temperature, and the mixture was stirred for 1 hour. In another dry 25 mL round-bottom flask, 2-bromotoluene (1 mmol, 3.3 equiv), diethyl ether (2 mL), and n-butyllithium (2.5 M inhexane, 3 equiv) were added under a nitrogen atmosphere at 0 °C, and the mixture was stirred for 1 hour. The freshly prepared 2-methylphenyllithium solution was slowly added to the indanone reaction solution cooled to 0 °C, and the reaction was continued at room temperature for 2 hours. After cooling the reaction solution to 0 °C, 6 M HCl (3 mL) was slowly added, and the mixture was stirred for 1 hour. The mixture was then extracted with ethyl acetate (3 × 3 mL). The organic phases were combined, washed with saturated brine (3 mL), dried over anhydrous sodium sulfate, and the filtrate was collected by filtration and concentrated using a rotary evaporator. The crude product was purified by silica gel column chromatography (eluting with petroleum ether) to give compound (R)-4h. The chemical structural formula of compound (R)-4h is as follows:

[0088]

[0089] Product: Compound (R)-4h is a white solid; 62 mg; yield 61%. Spec. Rot.: δ=7.43(s,1H),7.34–7.13(m,3H),6.53–6.49(m,1H),6.48–6.44(m,1H),6.41–6.37(m,3H),6.33–6.29(m,1H),6.28–6.22(m,1H),3.28–3 .14(m,2H),3.14–3.06(m,2H),3.05–2.98(m,1H),2.97–2.87(m,2H),2.70(dt,J=12.7,6.2Hz,1H),2.52–2.43(m,2H),2.22–2.08(m,3H). 13 C NMR (101MHz, DMSO-d6, 150℃): δ=147.3,144.7,144.3,138.5,138.3,137.7,135.9,134.7,133.3,133.1,132.9,13 2.3,132.1,130.2,129.4,129.3,127.7,127.7,125.7,125.3,34.5,33.5,31.6,31.5,20.0.HRMS(APCI)m / z:[M+H] + Calcd for C 26 H 25 337.1951; Found 337.1943.

[0090] 2. Synthesis of compound (R)-5h: In a dry 25mL round-bottom flask, under a nitrogen atmosphere and at room temperature, compound (R)-4h (0.25mmol, 1.0equiv), [Rh(COD)Cl]2 (74mg, 0.15mmol, 0.6equiv), and KO were added. t After adding Bu (42 mg, 0.375 mmol, 1.5 equiv) and anhydrous tetrahydrofuran (2 mL), the reaction mixture was stirred in a 70 °C oil bath for 20 hours. The reaction mixture was cooled to room temperature and concentrated using a rotary evaporator. The crude product was purified by column chromatography (5% triethylamine in petroleum ether solution) using alkalized silica gel (petroleum ether elution). No further purification was required before proceeding to the next reaction step. The chemical structure of compound (R)-5h is as follows:

[0091]

[0092] 3. Synthesis of planar chiral indene-rhodium complex (compound (R)-6h): In a dry 25 mL round-bottom flask, the previously prepared compound (R)-5h (0.25 mmol, 1.0 equiv), iodine (76 mg, 0.3 mmol, 1.2 equiv), and anhydrous diethyl ether (5 mL) were added at room temperature, and the mixture was stirred for 1 hour. The resulting brownish-black precipitate was collected by filtration through a Buchner funnel and washed with diethyl ether (10 mL). The precipitate was dried under vacuum to obtain compound (R)-6h. The chemical structural formula of compound (R)-6h is as follows:

[0093]

[0094] Product: Compound (R)-6h is a brownish-black solid; 56 mg; yield 44%. 1 H NMR (400MHz, CDCl3:DMSO-d6 (v / v=1:1)): δ=8.49(d,J=7.8Hz,2H),7.46–7.33(m,4H),7.30–7.20(m,2H),6.82–6.61(m,8H),6.44–6.36 (m,4H),6.29–6.20(m,2H),6.09–6.00(m,2H),3.38–3.20(m,4H),3.19–3.06(m,4H),2.89–2.72(m,6H),2.69(s,6H),2.18–2.05(m,2H). 13 C NMR (101MHz, CDCl3:DMSO-d6 (v / v=1:1)): δ=141.8,141.5,138.8,138.7,135 .6,135.0,134.9,133.4,132.9,131.9,131.0,130.9,130.4,129.5,129.2,12 5.5,119.0(d,J=3.3Hz),102.4(d,J=4.5Hz),94.3(d,J=6.5Hz),93.1(d,J=5 .2Hz),78.9(d,J=7.4Hz),34.8,34.4,33.3,33.2,21.0.HRMS(ESI)m / z:[M–I] + Calcd for C 52 H 46 I3Rh21256.8838; Found 1256.8835.

[0095] Example 9

[0096] This embodiment prepares a planar chiral indene-rhodium complex similar to that in Example 8. The method includes: using compound (R)-3a as a starting material to prepare compound (R)-6i (chemical structure shown below), the synthesis method is the same as in Example 8, except that 2-bromotoluene in the (R)-4h synthesis step is replaced with 2-bromoanisole (3.3 equiv). The obtained compound (R)-6i is a brownish-black solid; 90 mg; yield 74%. HRMS(ESI) m / z: [M–I] + Calcd for C 52 H 46 I3O2Rh21288.8736; Found1288.8744.

[0097]

[0098] Example 10

[0099] This embodiment prepares a planar chiral indene-rhodium complex similar to that in Example 8. The method includes: using compound (R)-3a as a starting material to prepare compound (R)-6j (chemical structure shown below), the synthesis method is the same as in Example 8, except that 2-bromotoluene in the (R)-4h synthesis step is replaced with 2-bromophenylethyl ether (3.3 equiv). The obtained compound (R)-6j is a brownish-black solid; 76 mg; yield 83%. HRMS(ESI) m / z: [M–I] + Calcd for C 54 H 50 I3O2Rh21316.9049; Found1316.9048.

[0100]

[0101] Example 11

[0102] This embodiment prepares a planar chiral indene-rhodium complex similar to that in Example 8. The method includes: using compound (R)-3a as a starting material to prepare compound (R)-6k (chemical structure shown below), the synthesis method is the same as in Example 8, except that 2-bromotoluene in the (R)-4h synthesis step is replaced with 1-bromo-2-isopropoxybenzene (3.3 equiv). The obtained compound (R)-6k is a brownish-black solid; 69 mg; yield 77%. HRMS(ESI) m / z: [M–I] + Calcd for C 56 H 54 I3O2Rh21344.9362; Found 1344.9367.

[0103]

[0104] Example 12

[0105] This embodiment prepares a planar chiral indene-rhodium complex similar to that in Example 8. The method includes: using compound (R)-3a as a starting material to prepare compound (R)-6l (chemical structure shown below), the synthesis method is the same as in Example 8, except that 2-bromotoluene in the (R)-4h synthesis step is replaced with 1-bromo-2,6-dimethoxybenzene (3.3 equiv). The obtained compound (R)-6l is a brownish-black solid; 26 mg; yield 16%. HRMS (ESI) m / z: [M–I] + Calcd for C 54 H 50 I3O4Rh21348.8948; Found 1348.8956.

[0106]

[0107] Example 13

[0108] This embodiment prepares a planar chiral indene-rhodium complex similar to that in Example 8. The method includes: using compound (R)-3a as a starting material to prepare compound (R)-6m (chemical structure shown below), the synthesis method is the same as in Example 8, except that 2-bromotoluene in the (R)-4h synthesis step is replaced with 3,5-di-tert-butylbromobenzene (3.3 equiv). The obtained compound (R)-6m is a brownish-black solid; 57 mg; yield 82%. HRMS(ESI)m / z: [M–I]+Calcd for C 66 H 74 I3Rh21453.1029; Found1453.1020.

[0109]

[0110] Example 14

[0111] This embodiment provides a third method for synthesizing planar chiral indene-rhodium metal complexes with a benzoindene skeleton, specifically including:

[0112] like Figure 4As shown, taking the synthesis of planar chiral indene rhodium complexes (R)-5n and (R)-6n as examples, the synthesis method includes: ① reacting chiral indene ketone (R)-3a with Cu(TFA)·×H2O and K2S2O8 to generate compound (R)-3b; ② reacting compound (R)-3b with hydrogen under palladium on carbon catalysis to generate compound (R)-3c; ③ reacting compound (R)-3c with nucleophile EtMgBr (or other nucleophiles for other examples) and acid dehydration to generate chiral indene ligand (R)-4n; ④ reacting chiral indene ligand (R)-4n with transition metal compound [Rh(COD)Cl]2 to generate compound (R)-5n; ⑤ reacting compound (R)-5n with elemental iodine to generate planar chiral indene rhodium complex (R)-6n.

[0113] The specific steps include:

[0114] 1. Synthesis of compound (R)-3b: In a dry 25 mL round-bottom flask, under a nitrogen atmosphere and at room temperature, compound (R)-3a (100 mg, 0.38 mmol, 1.0 equiv), Cu(TFA)·×H₂O (120 mg, 0.38 mmol, 1 equiv), K₂S₂O₈ (205 mg, 0.76 mmol, 2 equiv), and anhydrous DMF (5 mL) were added. The reaction mixture was then placed in an oil bath at 100 °C and stirred for 24 hours. After cooling the reaction mixture to room temperature, pure water (25 mL) was slowly added. Extraction was performed with ethyl acetate (3 × 5 mL). The organic phases were combined, washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, and the filtrate was collected and concentrated using a rotary evaporator. The crude product was purified by silica gel column chromatography (PE / EA = 8:1) to obtain compound (R)-3b. The chemical structure of compound (R)-3b is as follows:

[0115]

[0116] Product: Compound (R)-3b is a white solid; 74 mg; yield 71%. Spec. Rot. δ=6.68(d,J=7.6Hz,1H),6.63–6.58(m,2H),6.53(dd,J=7.9,2.0Hz,1H),6.45(dd,J=7.8,2.0Hz,1H),6.30–6.27(m,1H),6.25(dd,J=7.9,2.0 Hz,1H),5.65–5.58(m,1H),4.40–4.25(m,1H),3.54–3.33(m,2H),3.26 –3.17(m,1H),3.16–3.05(m,4H),3.02–2.91(m,1H),2.91–2.79(m,1H). 13 C NMR (101MHz, CDCl3): δ=194.2,150.9,143.5,141.7,140.1,139.4,139.3,139.0,136.9, 134.3,133.7,133.5,130.4,126.9,118.5,34.0,33.9,31.6,31.0.HRMS(ESI)m / z:[M+H] + Calcd for C 20 H 19 O275.1430; Found 275.1436.

[0117] 2. Synthesis of compound (R)-3c: In a dry 25 mL round-bottom flask, compound (R)-3b (74 mg, 0.27 mmol, 1.0 equiv), Pd / C (10% w / w, 0.05 equiv), and ethyl acetate (3 mL) were added at room temperature. The reaction atmosphere was then replaced with hydrogen gas, and a hydrogen balloon was attached. The reaction mixture was then placed in a 60 °C oil bath and stirred for 6 hours. After cooling to room temperature, the reaction mixture was filtered and concentrated using a rotary evaporator. The crude product was purified by silica gel column chromatography (PE / EA = 8:1) to obtain compound (R)-3c. The chemical structure of compound (R)-3c is as follows:

[0118]

[0119] Product: Compound (R)-3c is a white solid; 72 mg; yield 96%. Spec. Rot. δ=6.65(d,J=7.5Hz,1H),6.62–6.54(m,3H),6.46(dd,J=7.9,2.0Hz,1H),6.21(dd,J=8.0,1.9Hz,1H),4.29–4. 13(m,1H),3.23–3.02(m,6H),2.99–2.89(m,1H),2.87–2.78(m,1H),2.52–2.33(m,2H),1.40(d,J=7.2Hz,3H). 13 C NMR (101MHz, CDCl3): δ=209.5,153.9,141.0,140.2,139.1,139.0,137.2,137.1,133.9 ,133.7,133.3,130.7,127.1,41.5,34.1,33.9,31.5,31.3,15.2.HRMS(ESI)m / z:[M+H] + Calcd for C 20 H 21 O 277.1587; Found 277.1594.

[0120] 3. Synthesis of the chiral indene ligand (compound (R)-4n): In a dry 25 mL round-bottom flask, indene ketone (R)-3c (0.3 mmol, 1.0 equiv), THF (2 mL), and LaCl3·2LiCl (0.6 M in THF, 1 mL, 2 equiv) were added at room temperature and under a nitrogen atmosphere, and the mixture was stirred for 1 hour. After cooling the reaction solution to 0 °C, ethyl magnesium bromide (3 equiv) was slowly added. After continuing the reaction at room temperature for 2 hours, the reaction solution was cooled to 0 °C, 6 M HCl (3 mL) was slowly added, and the mixture was stirred for 1 hour. The mixture was extracted with ethyl acetate (3 × 3 mL). The organic phases were combined, washed with saturated brine (3 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated using a rotary evaporator. The crude product was purified by silica gel column chromatography (eluting with petroleum ether) to give compound (R)-4n. The chemical structure of compound (R)-4n is as follows:

[0121]

[0122] Product: Compound (R)-4n is a colorless liquid; 75 mg; yield 87%. Spec. Rot. δ=6.60–6.50(m,2H),6.43(d,J=7.7Hz,1H),6.36–6.28(m,2H),6.22–6.15(m,1H),3.54–3.38(m,1H),3.20–3.05(m, 2H),3.05–2.97(m,2H),2.97–2.80(m,3H),2.78–2.63(m,3H),2.54–2.41(m,1H),2.09(s,3H),1.10(t,J=7.6Hz,3H). 13 C NMR (101MHz, CDCl3): δ=146.3,143.3,141.3,139.1,138.8,137.6,134.3,134.0,133.0,132.5,13 1.8,129.0,128.2,125.5,42.3,35.7,34.2,33.6,32.2,19.9,14.04,13.95.HRMS(APCI)m / z:[M+H] + Calcd for C 22 H 25 289.1951; Found 289.1947.

[0123] 4. Synthesis of compound (R)-5n: In a dry 25 mL round-bottom flask, under a nitrogen atmosphere and at room temperature, add chiral indene ligand (compound (R)-4n) (0.25 mmol, 1.0 equiv), [Rh(COD)Cl]2 (74 mg, 0.15 mmol, 0.6 equiv), and KO t After adding Bu (42 mg, 0.375 mmol, 1.5 equiv) and anhydrous tetrahydrofuran (2 mL), the reaction solution was placed in an oil bath at 70 °C and stirred for 20 hours. The reaction solution was cooled to room temperature and concentrated using a rotary evaporator. The crude product was purified by alkaline silica gel column chromatography (5% triethylamine in petroleum ether solution) (eluting with petroleum ether) to give compound (R)-5n. The chemical structural formula of compound (R)-5n is as follows:

[0124]

[0125] Product: Compound (R)-5n is a yellow solid; 86 mg; yield 66%. Spec. Rot. δ=6.58–6.48(m,2H),6.32–6.21(m,2H),6.15–6.07(m,2H),4.93(d,J=4.2Hz,1H),3.67–3.33(m,3H),3.15–3.01(m,2H),2.99– 2.87(m,6H),2.82–2.70(m,1H),2.62–2.43(m,1H),2.36–2.22(m,4H),1.98–1.74(m,4H),1.70–1.56(m,4H),1.51–1.41(m,3H). 13 C NMR (101MHz, CDCl3): δ=138.6,138.3,131.9,131.8,131.5,131.1,128.6,127.8,127.6,115.0,110.9(d,J=2.2Hz),106.2(d,J=4.7Hz),9 4.8(d,J=3.1Hz),78.0(d,J=4.2Hz),71.4,71.3,67.7,67.6,35.2,34.5,33.3,33.2,32.0,31.4,20.1,15.3,13.1.HRMS(APCI)m / z:[M+H] + Calcd for C 30 H 36 Rh499.1867; Found 499.1863.

[0126] 4. Synthesis of compound (R)-6n: In a dry 25 mL round-bottom flask, compound (R)-5n (0.25 mmol, 1.0 equiv), iodine (76 mg, 0.3 mmol, 1.2 equiv), and anhydrous diethyl ether (5 mL) were added at room temperature, and the mixture was stirred for 1 hour. The resulting brownish-black precipitate was collected by filtration through a Buchner funnel, washed with diethyl ether (10 mL), and dried under vacuum to obtain compound (R)-6n. The chemical structural formula of compound (R)-6n is as follows:

[0127]

[0128] Product: Compound (R)-6n is a brownish-black solid; 85 mg; yield 77%. 1H NMR (400MHz, DMSO-d6:CDCl3 (v / v=1:1)): δ=6.79 (d, J=7.2Hz, 2H), 6.76–6.68 (m,4H),6.66(d,J=7.2Hz,2H),6.25(dd,J=7.9,1.8Hz,2H),6.16(dd,J=7.7,1 .8Hz,2H),5.79(s,2H),3.45–3.35(m,2H),3.30–3.17(m,6H),3.14–3.02(m,6 H),2.99–2.85(m,4H),2.67(s,6H),2.65–2.60(m,2H),1.54(t,J=7.6Hz,6H). 13 C NMR (101MHz, DMSO-d6: CDCl3 (v / v=1:1)): δ=140.4,139.7,139.3,138.8,136.4,135.6,132.8,132.5,131.5,129.9,115.0 (d,J=5.1Hz),11 4.5(d,J=6.1Hz),104.3(d,J=5.3Hz),91.8(d,J=6.1Hz),75.4(d,J=6.7Hz),35.0,34.3,33.5,32.7,20.5,15.0,13.5.HRMS(ESI)m / z:[M–I] + Calcd for C 44 H 46 I3Rh21160.8838; Found1160.8843.

[0129] Example 15

[0130] This embodiment prepares a planar chiral indene-rhodium complex similar to that of Example 14. The method includes: using compound (R)-3c obtained in Example 14 as a starting material to prepare compound (R)-6o (chemical structure shown below), the synthesis method is the same as in Example 14, except that ethyl magnesium bromide in the synthesis step of (R)-4n is replaced with phenyl magnesium bromide (3equiv). The obtained compound (R)-6o is a brownish-black solid; 106 mg; yield 76%. HRMS(ESI) m / z: [M–I] + Calcd forC 52 H 46 I3Rh21256.8838; Found1256.8830.

[0131]

[0132] Example 16

[0133] In this embodiment, the 15 planar chiral indene rhodium complexes (compounds (R)-6a to (R)-6o) prepared in the above embodiments were used as catalysts for asymmetric hydrocarbon activation reactions, and the test experiments are as follows:

[0134] Figure 5 The planar chiral indene-rhodium complexes (compounds (R)-6a to (R)-6o) prepared in Examples 1 to 15 are demonstrated as catalysts for the synthesis of P1 from A1 and B1. The specific steps include:

[0135] In a dry, threaded 15 mL pressure-resistant tube, compounds A1 (0.05 mmol, 1.0 equiv), B1 (0.075 mmol, 1.5 equiv), catalyst (compound (R)-6a, 1.3 mg, 0.001 mmol, 2 mol%), AgOAc (1.7 mg, 0.01 mmol, 20 mol%), CsOAc (2.5 mg, 0.025 mmol, 50 mol%), and anhydrous methanol (0.25 mL) were added at room temperature and stirred for 16 hours. The mixture was then concentrated using a rotary evaporator. The crude product was purified by silica gel column chromatography (PE / EA = 2:1) to give product P1. The ee value of the product was determined by HPLC.

[0136] Catalytic results with catalyst (R)-6a: Product P1 is a white solid; 7.1 mg; yield 67%, ee value 75%. HPLC IA 2-propanol / n-hexane = 20 / 80, flow rate 1.0 mL / min, column temp. 30℃, detection at 254 nm, retention times were 7.1 min (large peak) and 12.4 min (small peak). 1 H NMR (400MHz, CDCl3): δ=8.08(dd,J=7.9,1.5Hz,1H),7.42(td,J=7.5,1.5Hz,1H),7.29–7.22(m,1H),7.19(d,J=7.7Hz,1H),6.96(s,1H),3.79(d,J=8 .9Hz,1H),3.09(d,J=8.9Hz,1H),2.31–2.27(m,1H),2.27–2.25(m,1H),1. 69–1.55(m,3H),1.55–1.47(m,1H),1.39–1.27(m,1H),1.18–1.11(m,1H).

[0137] Following the method described above, other catalysts (compounds (R)-6b to (R)-6o) were used for the reaction of compound A1 with compound B1. The yield and ee value of product P1 are shown in Table 1 below.

[0138] Table 1 Experimental Results

[0139]

[0140]

[0141] Example 17

[0142] In this embodiment, the planar chiral indene-rhodium complex (compound (R)-6b) prepared in the above embodiment is used as a catalyst for the asymmetric hydrocarbon activation reaction, and the test experiments are as follows:

[0143] Figure 6 The reaction of A1 and B2 to synthesize P2 was demonstrated using a planar chiral indene-rhodium complex (compound (R)-6b) as a catalyst. The specific steps included:

[0144] In a dry, threaded 15 mL pressure-resistant tube, compounds A1 (0.1 mmol, 1.0 equiv), B2 (0.15 mmol, 1.5 equiv), catalyst (R)-6b (2.5 mg, 0.002 mmol, 2 mol%), AgOAc (8 mol%), CsOAc (5 mg, 0.05 mmol, 50 mol%), and anhydrous methanol (0.5 mL) were added at room temperature, and the mixture was stirred at 0°C for 24 hours. The mixture was then concentrated using a rotary evaporator. The crude product was purified by silica gel column chromatography (PE / EA = 2:1) to give product P2. The ee value of the product was determined by HPLC.

[0145] Catalytic results for catalyst (R)-6b: Product P2 is a white solid; 19.1 mg; yield 96%, ee. value 97%. Spec. Rot.: 2-propanol / n-hexane = 20 / 80, flow rate 1.0 mL / min, column temp. 30℃, detection at 254 nm, retention times were 18.5 min (large peak) and 20.1 min (small peak). 1HNMR (400MHz, CDCl3): δ = 8.07 (dd, J = 7.7, 1.4Hz, 1H), 7.49 (td, J = 7.5, 1.4Hz, 1H), 7.36 (td, J = 7.6, 1.3Hz, 1H), 7.28–7.20 (m, 1H), 6.26–5. 95(m,1H),5.91–5.71(m,2H),4.28(t,J=4.9Hz,1H),2.94(dt,J=12.3,4.0Hz,1H),2.38–2.16(m,2H),2.07–1.89(m,1H),1.75–1.64(m,1H).

[0146] Example 18

[0147] In this embodiment, the planar chiral indene-rhodium complex (compound (R)-6i) prepared in the above embodiment is used as a catalyst for the asymmetric hydrocarbon activation reaction, and the test experiments are as follows:

[0148] like Figure 7 As shown, Figure 7 The reaction of A2 and B3 to synthesize P3 is demonstrated by a planar chiral indene-rhodium complex (compound (R)-6i) as a catalyst. The specific steps include:

[0149] In a dry, threaded 15 mL pressure-resistant tube, benzoic acid A2 (0.1 mmol, 1.0 equiv), acetylene B3 (0.12 mmol, 1.2 equiv), catalyst (R)-6i (0.005 mmol, 5 mol%), AgOPiv (4.2 mg, 0.02 mmol, 20 mol%), Cu(OPiv)2 (26.6 mg, 0.1 mmol, 1 equiv), and trifluoroethanol (0.5 mL) were added at room temperature and stirred for 20 hours. The mixture was then concentrated using a rotary evaporator. The crude product was purified by silica gel column chromatography (PE / EA = 8:1) to obtain product P3. The ee value of the product was determined by HPLC.

[0150] Catalytic results with catalyst (R)-6i: Product P3 was a white solid, 47.4 mg, yield 98%, ee. value 94%. HPLC IF column (n-hexane / i-PrOH = 85:15, 1.0 mL / min, λ = 254 nm), retention times were 15.4 min (small peak) and 31.2 min (large peak). Spec. Rot. δ=8.49–8.42(m,1H),7.90(d,J=8.6Hz,1H),7.87–7.81(m,1H),7.59–7.51(m,1H),7.51–7.42(m,2H),7.38–7.29(m,5H),7.21–7.13(m,1H) ,7.12–7.02(m,2H),6.93–6.82(m,2H),6.78–6.72(m,1H),6.72–6.65(m,2H),4.97(d,J=12.2Hz,1H),4.89(d,J=12.2Hz,1H),3.75(s,3H). 13 C NMR (101MHz, CDCl3): δ=162.8,159.2,154.4,152.2,139.1,134.7,134.1,133.3,130.5,129.5,129.1,129.1,128.9,128.4,1 28.4,128.1,128.0,127.9,127.4,125.4,124.6,124.1,120.6,117.1,115.1,113.8,110.8,70.4,55.2.HRMS(ESI)m / z:[M+H] + Calcd forC 33 H 25 O4485.1747; Found 485.1743.

[0151] In summary, this application provides a synthetic intermediate (chiral indene ketone) of a chiral indene ligand without coordination arms, which is structurally easily modified and can stereospecifically complex metals. The chiral indene ligand in this application is highly modifiable, allowing for the synthesis of various chiral indene ligands without coordination arms, thus enabling the construction of a rich library of chiral indene ligands to meet the different chiral environments required by various reactions. Furthermore, this application utilizes the steric hindrance control of the chiral indene ligand itself to obtain a single planar chiral indene metal complex when a transition metal compound is complexed with the chiral indene ligand, eliminating the need to separate stereoisomers, significantly reducing the synthetic difficulty and costs. Its catalytic performance was demonstrated in three asymmetric hydrocarbon activation reactions, all exhibiting excellent yields and enantioselectivity.

[0152] The above description is only a preferred embodiment of this application. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of this application, and these improvements and modifications should also be considered within the scope of protection of this application.

Claims

1. (R)-configuration and (S)-configuration chiral indanone, wherein the (R)-configuration chiral indanone has the chemical structure shown in Formula (1), and the (S)-configuration chiral indanone has the chemical structure shown in Formula (2): Equation (1), Equation (2).

2. A method for synthesizing chiral indanone, the method comprising: Step 1: A chiral cyclopropionic acid consisting of (R)-configuration, (S)-configuration, or any ratio of (R)-configuration and (S)-configuration is condensed and reduced with cyclo()isopropyl malonate to generate cyclopropionic acid consisting of (R)-configuration, (S)-configuration, or any ratio of (R)-configuration and (S)-configuration. The (R)-configuration chiral cyclopropionic acid has the chemical structure shown in formula (3), the (S)-configuration chiral cyclopropionic acid has the chemical structure shown in formula (4), the (R)-configuration cyclopropionic acid has the chemical structure shown in formula (5), and the (S)-configuration cyclopropionic acid has the chemical structure shown in formula (6). Equation (3), Equation (4); Equation (5), Equation (6); Step 2: React the (S)-configuration, (R)-configuration, or any ratio of (S)-configuration and (R)-configuration of cyclopropionic acid in methanesulfonic acid to generate (R)-configuration, (S)-configuration, or any ratio of (R)-configuration and (S)-configuration of chiral indanone, respectively. The (R)-configuration chiral indanone has the chemical structure shown in Formula (1), and the (S)-configuration chiral indanone has the chemical structure shown in Formula (2): Equation (1), Equation (2).

3. A chiral indene ligand of (R)-configuration, (S)-configuration, or any ratio of (R)-configuration and (S)-configuration, wherein the (R)-configuration chiral indene ligand has a chemical structure as shown in Formula (7), and the (S)-configuration chiral indene ligand has a chemical structure as shown in Formula (8): Equation (7), Equation (8); in, In equations (7) and (8), R 1 Selected from alkyl, heteroalkyl, heteroaryl, or aryl; R 2 Selected from H, alkyl, heteroalkyl, heteroaryl, or aryl.

4. A method for synthesizing the chiral indene ligand of claim 3, the method comprising: The chiral indanone of claim 1 is reacted with a nucleophilic reagent and then dehydrated to prepare a chiral indanone ligand; the nucleophilic reagent is selected from Grignard reagent RMgX, organolithium reagent RLi, organocopper reagent R2CuLi, organozinc reagent R2Zn or organoaluminum reagent R3Al.

5. A planar chiral indene metal complex having a benzene-indene skeleton, comprising (R)-configuration, (S)-configuration, or any proportion thereof, wherein the (R)-configuration planar chiral indene metal complex has a chemical structure as shown in Formula (9), and the (S)-configuration planar chiral indene metal complex has a chemical structure as shown in Formula (10): Equation (9), Equation (10); in, In equations (9) and (10), R 1 Selected from alkyl, heteroalkyl, heteroaryl, or aryl; R 2 Selected from H, alkyl, heteroalkyl, heteroaryl, or aryl; M selected from rhodium, iridium, iron, cobalt, ruthenium, scandium, yttrium, or lanthanum; L selected from monoolefins, dienes, aromatics, halide anions, acid radical anions, cyclopentadienide anions, indene anions, o-aminobenzyl anions, carbon monoxide, phosphine ligands, nitrogen-containing aromatics, amines, or sulfur compounds; n represents the number of ligands, where n is an integer from 0 to 5.

6. A method for synthesizing the planar chiral indene metal complex of claim 5, the method comprising: The chiral indene ligand described in claim 3 is reacted with a transition metal compound to generate a planar chiral indene metal complex. In the planar chiral indene metal complex, L is selected from monoene or diene ligands, aromatic hydrocarbons, halide anions, acid radical anions, cyclopentadienide anions, indene anions, o-aminobenzyl anions, carbon monoxide, phosphine ligands, aza-aromatic hydrocarbons, amine compounds, or sulfur compounds. n represents the number of ligands, and n is an integer from 0 to 5.

7. A method for synthesizing the planar chiral indene metal complex of claim 5, the method comprising: Step a: React the chiral indene ligand according to claim 3 with a transition metal compound to generate a first planar chiral indene metal complex, wherein L in the first planar chiral indene metal complex is selected from a monoene or diene ligand; Step b: The first planar chiral indene metal complex described in step a is reacted with an oxidant, wherein the oxidant is a halogen, hydrogen halide, peroxide or metal oxidant, to generate a second planar chiral indene metal complex. In the second planar chiral indene metal complex, L represents a halide anion or an acid radical anion, and n represents the number of ligands, where n is an integer from 0 to 5.

8. The method according to claim 6 or 7, wherein the transition metal compound is selected from rhodium compounds, iridium compounds, iron compounds, cobalt compounds, ruthenium compounds, scandium compounds, yttrium compounds, or lanthanum compounds.

9. The application of the planar chiral indene metal complex of claim 5 or the planar chiral indene metal complex prepared by the method of any one of claims 6 to 8 as a catalyst in catalyzing asymmetric hydrocarbon activation reactions.

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