CN117362358A - Planar chiral iodo-metallocene, preparation method thereof and method for preparing polysubstituted planar chiral metallocene compound - Google Patents

Abstract

The invention discloses a planar chiral iodo-metallocene, a preparation method thereof and a method for preparing a polysubstituted planar chiral metallocene compound. The method takes simple N, N-dialkyl amino methyl metallocene (ferrocene, ruthenium dichloride) as an initial raw material, and under the action of a palladium catalyst, chiral amino acid, o-trifluoro acetyl iodobenzene derivative and alkali, stirring and reacting in an organic solvent at a certain temperature to obtain the 1, 2-disubstituted plane chiral iodo metallocene compound. The method has the advantages of cheap and easily obtained raw materials, mild reaction conditions, good universality of substrates, high yield and simple preparation process. The prepared 1, 2-disubstituted planar chiral iodo-metallocene can be used for further synthesizing other functionalized polysubstituted planar chiral metallocene compounds.

Description

A planar chiral iodometallocene and its preparation method and preparation of multi-substituted planar chiral Metallocene compounds

Technical field

The invention relates to a planar chiral iodometallocene and a preparation method thereof and a method for preparing a multi-substituted planar chiral metallocene compound, and belongs to the field of organic synthesis.

Background technique

Planar chiral ferrocene compounds have important applications in the fields of catalysis, materials, biomedicine and other fields. In particular, they can be widely used as efficient chiral ligands or catalysts in asymmetric catalytic reactions ([1]Fu,G.C.Acc .Chem.Res.2000,33,412;[2]Dai,L.-X.;Tu,T.;You,S.-L.;Deng,W.-P.;Hou,X.-L.Acc. Chem.Res.2003,36,659;[3]Atkinson,R.C.J.;Gibson,V.C.;Long,N.J.Chem.Soc.Rev.2004,33,313;[4]Arrayás,R.-G.;Adrio,J.;Carretero, J.-C. Angew. Chem. Int. Ed. 2006, 45, 7674; [5] Dai, L.-X.; Hou, X.-L. Chiral Ferrocenes in Asymmetric Catalysis, Wiley, Weinheim, 2010).

Planar chiral ferrocene compounds have significant advantages and large development space in the field of asymmetric catalysis and industrial applications. The design, development and synthesis of this type of ferrocene compounds has also become an important research direction in this field. So far, chemists have developed several methods and strategies for the synthesis of planar chiral ferrocene compounds. Among them, the traditional strategies mainly include the following four types: (1) Diastereoselective ortho-metalation induced by chiral prosthetic groups ([1] Battelle, LF; Bau, R.; Gokel, GW; Oyakawa, RT; Ugi ,IKJAm.Chem.Soc.1973,95,482;[2]Rebière,F.;Riant,O.;Ricard,L.;Kagan,HBangew.Chem.Int.Ed.1993,32,568;[3]Enders,D. ; Peters, R.; Lochtman, R.; Raabe, G. Angew. Chem. Int. Ed. 1999, 38, 2421; [4] Bolm, C.; Kesselgruber, M.; K.; Raabe, G. Organometallics 2000, 19, 1648.); (2) Enantioselective ortho-metalation using equivalent amounts of externally added chiral bases or chiral ligands ([1] Tsukazaki, M.; Tinkl ,M.;Roglans,A.;Chapell,BJ;Taylor,NJ;Snieckus,VJAm.Chem.Soc.1996,118,685;[2]Laufer,RS;Veith,U.;Taylor,NJ;Snieckus,V.Org . Lett.2000,2,629; [3] Genet, C.; Canipa, SJ; O'Brein, P.; Taylor, SJAm.Chem.Soc.2006,128,9336.); (3) Desymmetrization strategy ( [1] Yamazaki, Y.; Hosono, K. Agric. Biomol. Chem. 1990, 54, 2183; [2] Mercier, A.; Yeo, WC; Chou, J.; Chaudhuri, PD; Bernard-inelli, G .; Kündig, EPChem. Commun. 2009, 5227.); (4) Chiral resolution of racemates ([1] Alba, A.-N.; Rios, R. Molecules 2009, 14, 4747; [2] ]Ogasawara, M.; Arae, S.; Watanabe, S.; Nakajima, K.; Takahashi, T. ACS Catal.2016, 6, 1308. [3] Ogasawara, M.; Watanabe, S.; Nakajima, K .;Takahashi, TJAm.Chem.Soc.2010,132,2136.[4]Liu, C.-X.; Zhao, F.; Feng, Z.; Wang, Q.; Gu, Q.; You, S .-L. Nat. Synth. 2023, 2, 49.). However, these methods often have limitations such as poor functional group tolerance and low atom economy. In recent years, transition metal-catalyzed ortho-asymmetric CH functionalization of ferrocene has been rapidly developed and has become an important strategy to construct planar chiral ferrocene ([1] Zhu, D.-Y.; Chen, P .; ,50,351;[3]Huang,J.-P.;Gu,Q.;You,S.-L.Chin.J.Org.Chem.2018,38,51;[4]Liu,C.-X. ;Gu,Q.;You,S.-L.Trends Chem.2020,2,737;[5]Zhang,Z.-Z.;Huang,D.-Y.;Shi,B.-F.Org.Biomol. Chem.2022,20,4061;[6]Mou,Q.;Zhao,R.;Sun,B.Chem.Asian.J.2022,e202200818.[7]Zhou,L.;Cheng,H.-G. ;Li,L.;Wu,K.;Hou,J.;Jiao,C.;Deng,S.;Liu,Z.;Yu,J.-Q.;Zhou,Q.Nat.Chem.2023,15,815 .). The drawback is that this method requires a specific substrate and can only introduce a single functional group, and the types of functional groups that can be constructed currently are limited. In particular, the construction of ferrocene ortho-position carbon-heteroatom bonds has been rarely reported. Therefore, it is of great significance to develop a universal and efficient synthetic strategy to introduce a series of different functional groups ortho to ferrocene for the construction of planar chiral ferrocene.

Contents of the invention

In order to solve the deficiencies in the prior art, the present invention provides a planar chiral iodometallocene and a preparation method thereof and a method for preparing a multi-substituted planar chiral metallocene compound. The raw materials used in this method are cheap and easily available, the reaction conditions are mild, the substrate has good universality, the yield is high, and the preparation process is simple.

The technical solutions provided by the present invention are as follows:

In a first aspect, the present invention provides a method for synthesizing planar chiral iodometallocene, comprising the following steps:

A method for synthesizing planar chiral iodometallocene, which is characterized in that it includes the following steps:

Under the protection of inert gas, use N,N-dialkylaminomethylferrocene or ruthenium A as the starting material, under the action of iodinated reagent B, palladium catalyst C, chiral amino acid D and base E , stir in organic solvent F until the reaction is completed, and the reaction mixture is extracted, concentrated, and purified by column chromatography to obtain the 1,2-disubstituted planar chiral iodometallocene compound G as in the reaction formula;

Among them, the structure of A is:

R ¹ and R ² are two independent groups or connected to form one group; if they are independent groups, R ¹ and R ² are selected from C1-C6 alkyl groups; if R ¹ and R ² are connected to form one group , then the group is C1-C6 cycloalkyl or C1-C6 epoxyalkyl;

M is iron or ruthenium;

R ³ is selected from hydrogen, C6-C12 aryl, N, S substituted C5-C12 heterocyclic aryl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, cyano, C1- C6 aldehyde group, C2-C7 epoxy group, C2-C11 ester group, carboxyl group, amide group, -TMS or

The structure of B is:

R ⁴ is selected from any one or more of hydrogen, C1-C6 alkyl, C1-C6 alkoxy, and halogen. Preferably, the substitution position of R ⁴ is position 3, 4 or 5, where I is position 2.

The structure of G is:

Further, R ³ includes hydrogen; C1-C6 alkyl; C2-C6 alkenyl; C2-C6 alkynyl; C6-C12 aryl; C2-C11 ester group is -(CH ₂ ) _x -COOR′, x is an integer from 0 to 4, R′ is a C1-C6 alkyl group; N, S-substituted C5-C12 heterocyclic aryl groups include Halogen; cyano group; C1-C6 aldehyde group; acetal includes/> -TMS;/>

Further, the halogen in R ³ is fluorine, chlorine, bromine, or iodine.

Further, the palladium catalyst C is selected from Pd(OAc) ₂ , Pd(PPh ₃ ) ₂ (OAc) ₂ , Pd(TFA) ₂ , Pd(acac) ₂ , Pd(OPiv) ₂ , Pd(PhCN) ₂ Cl _2. Any one or more of Pd(MeCN) ₂ Cl ₂ , Pd(PPh ₃ ) ₂ Cl ₂ , PdCl ₂ , PdI ₂ , [Pd(allyl)Cl] ₂ .

Further, the structural formula of the chiral amino acid D is:

in:

i) R ⁵ is selected from any one of benzoyl, acetyl, benzyloxycarbonyl, tert-butoxycarbonyl, ester, C1-C6 alkyl, and benzyl;

ii) R ⁶ is selected from any one of C6-C12 aryl or C1-C6 alkyl.

Furthermore, in the chiral amino acid D, the ester group in R ⁵ is -COOR", R" is a C1-C6 alkyl group, C6-C12 aryl group; the C6-C12 aryl group in R ⁶ is -(CH ₂ ) _y -Ph, y is an integer from 0 to 4.

Further, the base E is selected from any one or more of sodium carbonate, potassium carbonate, cesium carbonate, sodium acetate, potassium acetate, cesium acetate, tripotassium phosphate, potassium formate, sodium hydroxide, and sodium tert-butoxide.

Further, the solvent F is selected from the group consisting of methanol, ethanol, isopropyl alcohol, tert-butyl alcohol, tetrahydrofuran, 2-methyltetrahydrofuran, diethyl ether, dimethyl ethylene glycol, methyl tert-butyl ether, and 1,4-dioxy. Hexanes, 1,3-dioxane, methylene chloride, 1,2-dichloroethane, chloroform, carbon tetrachloride, C4-12 saturated alkanes, C3-12 fluorinated or chlorinated alkanes, Benzene, toluene, xylene, trimethylbenzene, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, acetone, N-methylpyrrolidone, acetonitrile, C3-12 saturation Any one or more types of alkyl nitriles.

Furthermore, the reaction temperature is 25°C to 120°C.

Further, using N,N-dialkylaminomethylferrocene/ruthenium A as 1.0 molar equivalents, the dosage of iodinated reagent B is 2.0-4.0 molar equivalents, and the dosage of palladium catalyst C is 0.05-0.2 molar equivalents. , the dosage of chiral amino acid D is 0.1-0.5 molar equivalents and the dosage of base E is 1.0-3.0 molar equivalents.

Further, the inert gas includes one of nitrogen and argon.

The present invention uses easily available N,N-dialkylaminomethylferrocene/ruthenium as the starting material, and iodinated reagent under the action of palladium catalyst, chiral amino acid and alkali, at 25°C to 120 Stir the reaction in an organic solvent at ℃ to obtain 1,2-disubstituted planar chiral iodo metallocene. The raw materials used in this method are cheap and easily available, the reaction conditions are mild, the substrate has good universality, the yield is high, and the preparation process is simple.

The reaction path of the present invention is as follows:

In a second aspect, the present invention provides a planar chiral iodometallocene prepared by the method described in the first aspect.

In a third aspect, the present invention provides the use of the planar chiral iodometallocene prepared by the method described in the first aspect in the synthesis of other functional group disubstituted or trisubstituted planar chiral metallocene compounds.

1. Prepare 1,2-disubstituted planar chiral metallocene compounds and 1,2,3-trisubstituted planar chiral metallocene compounds. The steps are as follows:

(1) Preparation of 1,2-disubstituted planar chiral metallocene compounds, including the following steps:

Under the protection of inert gas, use ferrocene iodide or ruthenium G as the starting material, stir in the organic solvent F under the action of electrophile H and base E until the reaction is completed, extract and concentrate the reaction mixture, Purification by column chromatography yields the 1,2-disubstituted planar chiral metallocene compound as I in the reaction formula;

The reaction formula is as follows:

in:

H and the corresponding group R ⁷ are expressed as H/R ⁷ and are selected from: trialkylsilyl chloride/trialkylsilyl, diarylphosphine chloride/diarylphosphine, arylformyl chloride/arylmethyl Acyl, diaryl ketone/diaryl hydroxymethyl, alkyl chloroformate/alkoxy acyl, diaryl chlorophosphate/diaryloxyphosphono, diaryl sulfide/diaryl sulfide Ether group; the alkyl group is a C1-C6 alkyl group, and the aryl group is a C6-C12 aryl group.

Further, the reaction temperature is 25-120°C, and the reaction time is 1-72h.

Further, the protective gas is argon or nitrogen.

(2) The preparation method of 1,2,3-trisubstituted planar chiral metallocene compounds, the steps are as follows:

Under the protection of an inert gas, use 1,2-disubstituted ferrocene or ruthenium I as the starting material, and under the action of the electrophile H and the base E, stir in the organic solvent F until the end of the reaction. After extraction, concentration and column chromatography purification, the 1,2,3-trisubstituted planar chiral metallocene compound as J in the reaction formula is obtained.

The reaction formula is as follows:

in:

H and the corresponding group R ⁸ are expressed as H/R ⁸ and are selected from: trialkylsilyl chloride/trialkylsilyl, diarylphosphine chloride/diarylphosphine, arylformyl chloride/arylmethyl Acyl, diaryl ketone/diaryl hydroxymethyl, alkyl chloroformate/alkoxy acyl, diaryl chlorophosphate/diaryloxyphosphono, diaryl sulfide/diaryl sulfide Ether group; the alkyl group is a C1-C6 alkyl group, and the aryl group is a C6-C12 aryl group.

Further, the reaction temperature is 25-120°C, and the reaction time is 1-72h.

Further, the protective gas is argon or nitrogen.

2. A method for preparing 1,2,4-trisubstituted planar chiral metallocene, including the following steps:

Under the protection of inert gas, use ferrocene iodide or ruthenium G and aryl halide K as starting materials, under the action of palladium catalyst C, chiral amino acid D, norbornene derivative L and base E , stir the reaction in organic solvent F until the end of the reaction, filter, concentrate, and purify the reaction mixture by column chromatography to obtain a 1,2,4-trisubstituted planar chiral metallocene compound of formula M;

The reaction formula is as follows:

in:

R ⁹ is selected from C6-C12 aryl, N, S substituted C5-C12 heterocyclic aryl, C1-C6 alkyl, aldehyde, hydroxyl, amino, cyano, nitro, amide, C1-C6 alkoxy Base, one or more of C2-C6 alkenyl, C2-C6 alkynyl, halogen;

X is bromine or iodine;

m represents the number of R ⁹ , 0≤m≤3; when m=2 or 3, the substituent groups can be the same or different;

Ar ¹ is C6-C12 aromatic hydrocarbons and N, S-substituted C5-C12 heterocyclic aromatic hydrocarbons;

The structural formula of norbornene derivative L is:

in:

i) R ¹⁰ is the substituent on the left five-membered ring, n represents the number of substituents, 0≤n≤8; R ¹¹ is the substituent on the double bond, p represents the number of substituents, 0≤p≤2;

ii) R ¹⁰ and R ¹¹ are selected from C6-C12 aryl, N, S-substituted C5-C12 heterocyclic aryl, C1-C6 alkyl, aldehyde, carboxyl, hydroxyl, amino, cyano, nitro, amide Any one or more of base, C1-C6 alkoxy group, C1-C6 alkenyl group, C1-C6 alkynyl group or halogen;

iii) When the number of substituents on the left five-membered ring is 2 or more, they may be the same or different; when the number of substituents on the double bond is 2, they may be the same or different;

iv) The types of R ¹⁰ and R ¹¹ substituents may be the same or different.

Preferably, the structural formula of norbornene derivative L is

Further, the reaction temperature is 25-120°C, and the reaction time is 1-72h.

Further, the protective gas is argon or nitrogen.

The beneficial effects of the present invention are as follows:

1. The main raw material N,N-alkylaminomethylferrocene/ruthenium involved in the present invention is a commercial raw material (its derivatives only need to be processed quickly in one or two steps using simple commercial raw materials ferrocene/ruthenium). synthesis);

2. The iodinated reagent involved in the present invention only requires one step of rapid synthesis;

3. The method of the present invention has very good enantioselectivity, and the ee value of the obtained product is as high as 99%;

4. The catalyst used in the reaction involved in the method of the present invention is a relatively cheap metal palladium salt, which is an important improvement and supplement compared to the equivalent amount of organometallic reagents used in other synthesis methods;

5. The planar chiral iodometallocene prepared by the present invention can be used to further synthesize other functional group disubstituted or trisubstituted planar chiral metallocene compounds.

Detailed ways

The present invention will be further described below through specific examples. It is worth noting that the present invention is not limited to the following examples.

Example 1: Preparation of Compound G-1

Place a stirring bar of appropriate size into a dry 10 mL Schlenk bottle, then add palladium acetate (2.2 mg, 0.01 mmol, 0.1 equiv), N-(tert-butoxycarbonyl)-L-valine (6.5 mg, 0.03 mmol, 0.3 equiv) and potassium carbonate (27.6 mg, 0.2 mmol, 2.0 equiv). After replacing the argon gas three times through a double row tube, add dry N, N-dimethylformamide DMF (0.9 mL ), dry dimethyl sulfoxide (0.1mL), N,N-dimethylaminomethylferrocene (24.3mg, 0.1mmol, 1.0equiv), 2,2,2-trifluoromethyl-1 -(2-iodo-3-methyl)phenylethanone (94.2 mg, 0.3 mmol, 3.0 equiv), and then the reaction system was stirred at 80°C for 18 hours. After the reaction was completed, it was cooled to room temperature, saturated sodium carbonate solution was added to the reaction system to quench the reaction, and extracted with ethyl acetate. Three times, the organic phases were combined and washed with saturated brine. The organic phase was dried over anhydrous sodium sulfate. After filtration, the solvent was removed under reduced pressure and separated by column chromatography to obtain product G-1 (red oily liquid, yield 68%). ¹ H NMR (600MHz, CDCl ₃ ): δ4.31 (dd, J＝2.4, 1.4Hz, 1H), 4.20 (dd, J＝2.7, 1.4Hz, 1H), 4.16 (t, J＝2.5Hz, 1H ),3.98(t,J＝2.0Hz,2H),3.94(dt,J＝6.2,1.7Hz,2H),3.34(d,J＝13.0Hz,1H),3.30(d,J＝13.0Hz,1H ), 2.23 (s, 6H), 1.94 (s, 3H); ¹³ C NMR (150MHz, CDCl ₃ ): δ85.8,84.7,75.8,72.8,72.4,71.2,71.1,70.0,69.5,58.5,47.3, 45.2,13.8; HRMS (ESI+FTMS):calc'd forC ₁₃ H ₁₇ FeIN ⁺ [M+H ⁺ ]369.9750, found 369.9746; HPLC: 98%ee, Daicel Chiralpak OD-Hcolumn, Hexanes/IPA＝99/1 ,1mL/min, λ=254nm, t _R (major)=9.30min, t _R (minor)=7.48min;/> -12.72(c 0.21,CHCl ₃ ).

Example 2: Preparation of Compound G-2

The operating steps are the same as in Example 1, except that the ferrocene substrate used is: 1-dimethylaminomethyl-1′-methylferrocene (25.7 mg) to obtain compound G-2 (red oily liquid , yield 71%). ¹ H NMR (600MHz, CDCl ₃ ) δ4.31 (dd, J＝2.4, 1.4Hz, 1H), 4.20 (dd, J＝2.7, 1.4Hz, 1H), 4.16 (t, J＝2.5Hz, 1H) ,3.98(t,J＝2.0Hz,2H),3.94(dt,J＝6.2,1.7Hz,2H),3.34(d,J＝13.0Hz,1H),3.30(d,J＝13.0Hz,1H) ,2.23(s,6H),1.94(s,3H); ¹³ C NMR (150MHz, CDCl ₃ )δ85.8,84.7,75.8,72.8,72.4,71.2,71.1,70.0,69.5,58.5,47.3,45.2, 13.8; HRMS(ESI+FTMS):calc'd for C ₁₄ H ₁₉ FeIN ⁺ [M+H ⁺ ]383.9906,found 383.9899.HPLC:98%ee,Daicel Chiralpak OD-H column,Hexanes/IPA/Et ₂ NH ＝99/1/0.1, 0.7mL/min, λ＝254nm, t _R (major)＝9.93min, t _R (minor)＝7.82min; -16.68(c0.44,CHCl ₃ ).

Example 3: Preparation of Compound G-3

The operating steps are the same as in Example 1, except that the ferrocene substrate used is: 1-dimethylaminomethyl-1'-ethylferrocene (27.1 mg) to obtain compound G-3 (red oily liquid , yield 55%). ¹ H NMR (400MHz, CDCl ₃ ) δ4.33 (dd, J＝2.4, 1.4Hz, 1H), 4.22 (dd, J＝2.7, 1.4Hz, 1H), 4.17 (t, J＝2.6Hz, 1H) ,3.97(td,J＝3.6,1.7Hz,4H),3.35(d,J＝13.0Hz,1H),3.30(d,J＝13.0Hz,1H),2.33(qd,J＝7.5,1.2Hz, 2H), 2.23 (s, 6H), 1.15 (t, J = 7.5Hz, 3H); ¹³ C NMR (100MHz, CDCl ₃ ) δ 92.8, 84.7, 75.6, 71.6, 71.5, 71.4, 70.3, 69.8, 69.4 ,58.5,47.1,45.2,21.5,15.1; HRMS(ESI+FTMS):calc'd forC ₁₅ H ₂₁ FeIN ⁺ [M+H ⁺ ]398.0063, found 398.0063; HPLC: 97%ee, Daicel Chiralpak OD-Hcolumn, Hexanes/IPA/Et ₂ NH=99/1/0.1, 0.7mL/min, λ=254nm, t _R (major)=9.19min, t _R (minor)=6.96min; -17.74(c 0.54,CHCl ₃ ).

Example 4: Preparation of Compound G-4

The operating steps are the same as in Example 1, except that the ferrocene substrate used is: 1-dimethylaminomethyl-1′-isopropylferrocene (28.5 mg) to obtain compound G-4 (red oily liquid, yield 60%). ¹ H NMR (400MHz, CDCl ₃ ) δ4.35 (dd, J＝2.5, 1.4Hz, 1H), 4.24 (dd, J＝2.6, 1.4Hz, 1H), 4.18 (t, J＝2.5Hz, 1H) ,4.02(q,J＝1.7Hz,1H),3.97(dt,J＝2.7,1.4Hz,1H),3.97-3.90(m,2H),3.35(d,J＝13.0Hz,1H),3.31( d, J＝13.1Hz, 1H), 2.64 (hept, J＝6.9Hz, 1H), 2.22 (s, 6H), 1.18 (s, 3H), 1.16 (s, 3H); ¹³ C NMR (100MHz, CDCl ₃ )δ98.5,84.7,75.5,72.1,71.7,70.5,69.8,69.3,68.3,58.6,47.0,45.2,27.1,23.8,23.7; HRMS(ESI+FTMS):calc'd for C ₁₅ H ₂₁ FeIN ⁺ [M+H ⁺ ]398.0063, found398.0063; HPLC: 98%ee, Daicel Chiralpak OD-H column, Hexanes/IPA/Et ₂ NH＝99/1/0.1, 0.5mL/min, λ＝254nm, t _R (major)=12.81min, t _R (minor)=9.08min; -36.26(c0.60,CHCl ₃ ).

Example 5: Preparation of Compound G-5

The operating steps are the same as in Example 1, except that the ferrocene substrate used is: 1-dimethylaminomethyl-1′-benzylferrocene (33.3 mg) to obtain compound G-5 (red oily liquid , yield 57%). ¹ H NMR (400MHz, CDCl ₃ ) δ7.29-7.23(m,2H),7.21-7.12(m,3H),4.36(dd,J＝2.5,1.3Hz,1H),4.24(dd,J＝2.6 ,1.4Hz,1H),4.18(t,J＝2.5Hz,1H),4.01(ddd,J＝6.1,4.8,2.3Hz,4H),3.67(s,2H),3.35(s,1H),3.29 (s,1H),2.23(s,6H); ¹³ C NMR (100MHz, CDCl ₃ ) δ141.4,128.4,126.2,89.5,84.9,75.8,72.5,72.0,71.9,71.5,70.1,69.6,58.5,47.2, 45.2, 35.1; HRMS (ESI+FTMS):calc'd forC ₂₀ H ₂₃ FeIN ⁺ [M+H ⁺ ]460.0219, found 460.0217; HPLC: 98%ee, Daicel Chiralpak OD-Hcolumn, Hexanes/IPA/Et ₂ NH ＝99/1/0.1, 0.7mL/min, λ＝254nm, t _R (major)＝13.89min, t _R (minor)＝11.01min; -31.21(c 0.70,CHCl ₃ ).

Example 6: Preparation of Compound G-6

The operating steps are the same as in Example 1, except that the ferrocene substrate used is: 1-dimethylaminomethyl-1′-(2-ethoxycarbonylethyl)ferrocene (33.3 mg) to obtain the compound G-6 (yellow oily liquid, yield 56%). ¹ H NMR (400MHz, CDCl ₃ ): δ4.34 (dd, J＝2.4, 1.4Hz, 1H), 4.23 (dd, J＝2.6, 1.4Hz, 1H), 4.17 (t, J＝2.6Hz, 1H ),4.13(q,J＝7.1Hz,2H),3.99(d,J＝1.7Hz,3H),3.95(q,J＝1.7Hz,1H),3.34(d,J＝13.0Hz,1H), 3.29(d,J＝13.0Hz,1H),2.68-2.61(m,2H),2.49(dd,J＝8.6,6.5Hz,2H),2.22(s,6H),1.25(t,J＝7.2Hz ,3H); ¹³ C NMR (100MHz, CDCl ₃ ): δ173.1,89.1,84.9,75.7,72.0,71.9,71.6,70.9,70.0,69.5,60.6,58.5,47.0,45.2,35.9,24.1,14.4; HRMS(ESI+FTMS):calc'd for C ₁₈ H ₂₅ FeINO2 ⁺ [M+H ⁺ ]470.0274, found 470.0272; HPLC: 96%ee, DaicelChiralpak OD-Hcolumn, Hexanes/IPA/Et ₂ NH＝99/1 /0.1,0.7mL/min, λ=254nm, _{t R} (major)=21.01min, t _R (minor)=18.50min; -45.98(c 0.59,CHCl ₃ ).

Example 7: Preparation of Compound G-7

The operating steps are the same as in Example 1, except that the ferrocene substrate used is: 1-dimethylaminomethyl-1′-(2-cyano)ferrocene (29.6 mg) to obtain compound G-7 (yellow oily liquid, yield 67%). ¹ H NMR (400MHz, CDCl ₃ ): δ4.35 (dd, J＝2.5, 1.3Hz, 1H), 4.26 (dd, J＝2.7, 1.4Hz, 1H), 4.20 (t, J＝2.5Hz, 1H ),4.07(q,J＝2.5,2.0Hz,3H),4.00(q,J＝1.6Hz,1H),3.32(d,J＝13.0Hz,1H),3.27(d,J＝13.0Hz,1H ), 2.70 (t, J = 7.5Hz, 2H), 2.50 (t, J = 7.2Hz, 2H), 2.22 (s, 6H); ¹³ C NMR (100MHz, CDCl ₃ ): δ 119.5, 86.5, 85.3 ,75.8,72.2,72.1,71.8,70.8,70.0,69.5,58.4,47.0,45.2,25.1,19.3; HRMS(ESI+FTMS):calc'd for C ₁₆ H ₂₀ FeIN ₂ ⁺ [M+H ⁺ ]423.0015 , found423.0009; HPLC:>99%ee, Daicel Chiralpak IA column, Hexanes/IPA/Et ₂ NH＝97/3/0.1, 0.7mL/min, λ＝254nm, t _R (major)＝22.48min; -41.00(c 0.66,CHCl ₃ ).

Example 8: Preparation of Compound G-8

The operating steps are the same as in Example 1, except that the ferrocene substrate used is: 1-dimethylaminomethyl-1'-bromoferrocene (32.2 mg) to obtain compound G-8 (yellow oily liquid, Yield 49%). ¹ H NMR (400MHz, CDCl ₃ ): δ4.44(t,J＝1.9Hz,1H), 4.30(td,J＝2.6,1.3Hz,3H), 4.25(dt,J＝2.6,1.3Hz,1H ),4.06(td,J＝2.6,1.3Hz,1H),4.03(td,J＝2.6,1.4Hz,1H),3.39(d,J＝13.1Hz,1H),3.31(d,J＝13.1Hz ,1H),2.24(s,6H); ¹³ C NMR (100MHz, CDCl ₃ ): δ86.5,78.8,77.4,73.9,73.1,72.0,71.8,71.6,71.0,57.9,46.7,45.3; HRMS (ESI +FTMS):calc'd for C ₁₃ H ₁₆ BrFeIN ⁺ [M+H ⁺ ]447.8855, found447.8852; HPLC: 98%ee, Daicel Chiralpak OD-H column, Hexanes/IPA/Et ₂ NH＝99/1 /0.1,0.7mL/min, λ=254nm, _{t R} (major)=11.11min, t _R (minor)=8.74min; -4.23(c0.52,CHCl ₃ ).

Example 9: Preparation of Compound G-9

The operating steps are the same as in Example 1, except that the ferrocene substrate used is: 1-dimethylaminomethyl-1'-phenylferrocene (31.9 mg) to obtain compound G-9 (yellow oily liquid , yield 59%). ¹ H NMR (400MHz, CDCl ₃ ): δ7.48 (d, J = 7.4Hz, 2H), 7.32 (t, J = 7.6Hz, 2H), 7.22 (t, J = 7.3Hz, 1H), 4.58 ( d,J＝2.9Hz,1H),4.51(d,J＝2.6Hz,1H),4.30-4.29(m,1H),4.25(d,J＝2.8Hz,1H),4.17(d,J＝2.6 ¹³ CNMR (100MHz, CDCl ₃ ): δ137.2,128.6,126.5,126.3,87.2,85.0,76.5,72.7(2),70.9,70.4,70.1,69.2,57.7,47.1,45.1; HRMS(ESI+FTMS):calc'dforC ₁₉ H ₂₁ FeIN ⁺ [M+H ⁺ ]446.0063, found446.0059; HPLC: 98%ee, DaicelChiralpakOD-Hcolumn, Hexanes/IPA/Et ₂ NH＝99.5/0.5/0.1, 0.5mL/min, λ＝254nm, t _R (major)=24.96min, t _R (minor)=23.04min; 44.37(c0.59,CHCl ₃ ).

Example 10: Preparation of Compound G-10

The operating steps are the same as in Example 1, except that the ferrocene substrate used is: 1-dimethylaminomethyl-1′-(4-methoxycarbonylphenyl)ferrocene (37.7 mg) to obtain the compound G-10 (red oily liquid, yield 52%). ¹ H NMR (400MHz, CDCl ₃ ): δ8.02-7.95 (m, 2H), 7.54-7.49 (m, 2H), 4.62 (dt, J＝2.7, 1.4Hz, 1H), 4.57 (dt, J＝ 2.8,1.4Hz,1H),4.37(td,J＝2.5,1.2Hz,1H),4.33(td,J＝2.6,1.3Hz,1H),4.24(dd,J＝2.5,1.4Hz,1H), 4.15(dd,J＝2.6,1.4Hz,1H),4.10(t,J＝2.5Hz,1H),3.92(s,3H),3.01(d,J＝13.2Hz,1H),2.96(d,J ＝13.2Hz,1H),2.12(s,6H); ¹³ C NMR (100MHz, CDCl ₃ ): δ167.2,143.0,129.9,127.9,126.0,85.5,85.2,76.8,73.4(2),71.0,70.4(2) ),69.8,57.7,52.2,47.1,45.1; HRMS(ESI+FTMS):calc'dforC ₂₁ H ₂₃ FeINO ₂ ⁺ [M+H ⁺ ]504.0117, found504.0114; HPLC: 99%ee, DaicelChiralpakOD-Hcolumn, Hexanes/IPA/Et ₂ NH=99/1/0.1, 0.7mL/min, λ=254nm, _tR (major)=27.55min, _tR (minor)=21.69min; -62.73(c0.67,CHCl ₃ ).

Example 11: Preparation of Compound G-11

The operating steps are the same as in Example 1, except that the ferrocene substrate used is: 1-dimethylaminomethyl-1′-(4-methylphenyl)ferrocene (33.3 mg) to obtain compound G. -11 (red oily liquid, yield 53%). ¹ H NMR (400MHz, CDCl ₃ ): δ7.37 (d, J = 7.8 Hz, 2H), 7.13 (d, J = 7.7 Hz, 2H), 4.59-4.51 (m, 1H), 4.48 (dd, J ＝2.9,1.6Hz,1H),4.26(q,J＝2.1Hz,1H),4.23(dq,J＝3.8,1.9Hz,2H),4.14(t,J＝1.9Hz,1H),4.09(t ,J＝2.5Hz,1H),3.04(d,J＝13.2Hz,1H),2.99(d,J＝13.2Hz,1H),2.33(s,3H),2.13(s,6H); ¹³ C NMR (100MHz, CDCl ₃ ): δ136.2,134.1,129.3,126.2,87.5,85.1,76.5,72.6,72.5,70.9,70.4,69.8,69.1,47.0,45.1,21.3; HRMS(ESI+FTMS):calc'd for C ₂₀ H ₂₃ FeIN ⁺ [M+H ⁺ ]460.0219, found 460.0216; HPLC: 98%ee, Daicel Chiralpak OD-H column, Hexanes/IPA/Et ₂ NH＝99/1/0.1, 0.7mL/min, λ =254nm, t _R (major) = 11.07min, t _R (minor) = 9.87min; -62.73(c 0.67,CHCl ₃ ).

Example 12: Preparation of Compound G-12

The operating steps are the same as in Example 1, except that the ferrocene substrate used is: 1-dimethylaminomethyl-1′-(4,4,5,5-tetramethyl-1,3-dioxo Cyclopent-2-yl)ferrocene (37.1 mg) was used to obtain compound G-12 (red oily liquid, yield 52%). ¹ H NMR (400MHz, CDCl ₃ ) δ5.84 (s, 1H), 4.46-4.39 (m, 1H), 4.30 (dd, J = 2.7, 1.4Hz, 1H), 4.25 (t, J = 2.5Hz, 2H),4.23(dd,J＝2.6,1.3Hz,1H),4.10(q,J＝2.2Hz,1H),4.02(q,J＝2.3Hz,1H),3.47(d,J＝13.1Hz, 1H),3.31(d,J＝13.1Hz,1H),2.22(s,6H),1.26(s,3H),1.25(s,3H),1.22(s,3H),1.21(s,3H); ¹³ C NMR (100MHz, CDCl ₃ ) δ98.4,87.8,85.5,82.5,82.4,75.7,73.7,72.5,70.2(2C),70.1,70.0,58.3,46.7,45.2,24.3(2C),22.2(2C) ); HRMS (ESI+FTMS):calc'd for C ₂₀ H ₂₉ FeINO ₂ ⁺ [M+H ⁺ ]498.0587, found 498.0588; HPLC: 98%ee, Daicel Chiralpak OD-H column, Hexanes/IPA/Et ₂ NH=99/1/0.1, 0.7mL/min, λ=254nm, t _R (major)=7.80min, t _R (minor)=7.01min; -4.17 (c 0.86, CHCl ₃ ).

Example 13: Preparation of Compound G-13

The operating steps are the same as in Example 1, except that the ferrocene substrate used is: 1-dimethylaminomethyl-1'-methoxycarbonylferrocene (30.1 mg) to obtain compound G-13 (red oily liquid, yield 39%). ¹ H NMR (400MHz, CDCl ₃ ): δ4.72 (d, J = 2.6 Hz, 1H), 4.66 (d, J = 2.5 Hz, 1H), 4.45 (d, J = 2.5 Hz, 1H), 4.34 ( d,J＝2.6Hz,1H),4.31(q,J＝2.6Hz,2H),4.26(d,J＝2.7Hz,1H),3.84(s,3H),3.29(d,J＝13.1Hz, 1H), 3.24 (d, J = 13.1Hz, 1H), 2.22 (s, 6H); ¹³ C NMR (100MHz, CDCl ₃ ): δ 170.7, 86.3, 76.4, 75.3, 74.5, 73.9, 73.9, 72.7, 70.8,70.5,57.7,51.8,46.6,45.2; HRMS(ESI+FTMS):calc'd forC ₁₅ H ₁₉ FeINO ₂ ⁺ [M+H ⁺ ]427.9804, found 427.9804; HPLC: 98%ee, Daicel Chiralpak IAcolumn, Hexanes/IPA/Et ₂ NH=99/1/0.1, 0.7mL/min, λ=254nm, t _R (major)=22.40min, t _R (minor)=25.77min; 29.43 (c 0.44, CHCl ₃ ).

Example 14: Preparation of Compound G-14

The operating steps are the same as Example 1, except that the ferrocene substrate used is: 1-dimethylaminomethyl-1′-(2-ethoxycarbonyl-1-vinyl)ferrocene (34.1 mg) , compound G-14 (red oily liquid, yield 53%) was obtained. ¹ HNMR (400MHz, CDCl ₃ ): δ7.45 (d, J = 15.8Hz, 1H), 6.06 (d, J = 15.8Hz, 1H), 4.39 (t, J = 1.8Hz, 1H), 4.38-4.36 (m,1H),4.35(d,J＝2.4Hz,1H),4.32(t,J＝2.3Hz,2H),4.28(d,J＝2.5Hz,1H),4.26-4.19(m,3H) ,3.23(d,J＝13.3Hz 1H), 3.19(d,J＝13.3Hz 1H), 2.20(s,6H),1.33(t,J＝7.1Hz,3H); ¹³ C NMR (100MHz, CDCl ₃ ): δ167.1,143.9,116.6,86.1,80.7,76.6,74.5,74.4,72.2,71.5,70.8,70.4,60.4,58.2,46.8,45.2,14.5; HRMS(ESI+FTMS):calc'd forC ₁₈ H ₂₃ FeINO2 ⁺ [M+H ⁺ ]468.0117, found 468.0108; HPLC: 98%ee, Daicel Chiralpak IAcolumn, Hexanes/IPA/Et ₂ NH＝99/1/0.1, 0.7mL/min, λ＝254nm, t _R (major )=25.78min, t _R (minor)=28.73min; 48.67 (c 0.47, CHCl ₃ ).

Example 15: Preparation of Compound G-15

The operating steps are the same as in Example 1, except that the ferrocene substrate used is: 1-dimethylaminomethyl-1′-(trimethylsilyl)ferrocene (31.5 mg) to obtain compound G- 15 (red oily liquid, yield 50%). ¹ H NMR (400MHz, CDCl ₃ ): δ4.44-4.38(m,1H),4.32-4.28(m,1H),4.24-4.17(m,3H),4.13-4.08(m,1H),4.06( ¹³ C NMR (100MHz, CDCl ₃ ): δ 84.9, 77.5, 76.7, 76.0, 75.2, 74.6, 73.7, 69.5, 69.1, 58.8, 46.7, 45.2, 0.0; HRMS (ESI+FTMS): calc'd for C ₁₆ H ₂₅ FeINSi ⁺ [M+H ⁺ ]442.0145, found442.0147; HPLC: 98%ee, Daicel Chiralpak OD-H column, Hexanes/IPA＝99/1, 1.0mL/min, λ＝254nm, t _R (major) =8.85min, t _R (minor) =4.89min; -62.73(c 0.67,CHCl ₃ ).

Example 16: Preparation of Compound G-16

The operating steps are the same as in Example 1, except that the ferrocene substrate used is: 1-dimethylaminomethyl-1′-(diphenylhydroxymethyl)ferrocene (42.5 mg) to obtain compound G. -16 (yellow oily liquid, yield 75%). ¹ H NMR (400MHz, CDCl ₃ ): δ7.48-7.26 (m, 10H), 4.49 (d, J = 2.4Hz, 1H), 4.42 (d, J = 2.5Hz, 1H), 4.38 (d, J ＝3.2Hz,1H),4.23(d,J＝2.5Hz,1H),4.19-4.13(m,1H),4.11(d,J＝2.6Hz,1H),4.06(d,J＝3.2Hz,1H ), 3.30 (d, J = 13.8Hz, 1H), 3.23 (d, J = 13.8Hz, 1H), 2.42 (s, 6H); ¹³ C NMR (100MHz, CDCl ₃ ): δ 147.6, 147.4, 127.7 (2 ),127.1,127.0(2),126.9,99.2,86.3,77.7,76.7,75.1,72.3,71.2,70.6,69.4,69.2,58.6,46.0,45.5; HRMS(ESI+FTMS):calc'd forC ₂₆ H ₂₇ FeINO ⁺ [M+H ⁺ ]552.0481, found 552.0480; HPLC: 98%ee, Daicel Chiralpak OD-Hcolumn, Hexanes/IPA/Et ₂ NH＝99/1/0.1, 0.7mL/min, λ＝254nm, t _R (major)=13.51min, t _R (minor)=15.19min; -62.73(c 0.67,CHCl ₃ ).

Example 17: Preparation of Compound G-17

The operating steps are the same as in Example 1, except that the ferrocene substrate used is: 4-(1,3-dioxolane-2-yl)piperidinemethylferrocene (34.1 mg) to obtain compound G. -17 (yellow oily liquid, yield 75%). ¹ H NMR (400MHz, CDCl ₃ ): δ4.41 (dd, J＝2.5, 1.4Hz, 1H), 4.31 (dd, J＝2.6, 1.4Hz, 1H), 4.21 (t, J＝2.5Hz, 1H ),4.10(s,5H),3.92(s,4H),3.54(d,J＝13.3Hz,1H),3.43(d,J＝13.3Hz,1H),2.60(q,J＝7.1,5.3Hz , 2H), 2.49 (dt, J＝11.5, 5.8Hz, 2H), 1.70 (q, J＝5.9, 5.5Hz, 4H); ¹³ C NMR (100MHz, CDCl ₃ ): δ 107.3, 84.8, 74.9, 71.7,69.3,69.0,64.3,57.3,51.0,46.6,34.9; HRMS(ESI+FTMS):calc'd for C ₁₈ H ₂₃ FeINO ₂ ⁺ [M+H ⁺ ]468.0117, found 468.0118; HPLC: 99%ee ,Daicel Chiralpak OD-H column, Hexanes/IPA/Et ₂ NH＝99/1/0.1, 0.7mL/min, λ＝254nm, t _R (major)＝16.69min, t _R (minor)＝14.70min; -62.73(c 0.67,CHCl ₃ ).

Example 18: Preparation of Compound G-18

The operating steps are the same as in Example 1, except that the ferrocene substrate used is: N,N-dimethylaminomethylruthenium (28.8 mg) to obtain compound G-18 (yellow oily liquid, yield 33 %). ¹ H NMR (600MHz, CDCl ₃ ) δ4.84(t,J＝1.7Hz,1H),4.64(t,J＝1.8Hz,1H),4.53(t,J＝2.4Hz,1H),4.51(s ,5H),3.24(d,J＝13.2Hz,1H),3.19(d,J＝13.2Hz,1H),2.28(s,6H); ¹³ C NMR (150MHz, CDCl ₃ )δ89.3,77.8, 73.6,71.8,71.7,58.8,45.3,41.6; HRMS(ESI+FTMS):calc'd for C ₁₃ H ₁₇ INRu ⁺ [M+H ⁺ ]415.9444, found 415.9444; HPLC: 91%ee, Daicel Chiralpak OD- H column, Hexanes/IPA/Et ₂ NH=99/1/0.1, 0.7mL/min, λ=254nm, _tR (major)=11.98min, _tR (minor)=10.71min; 61.95(c 1.28, CHCl ₃ ).

Example 19: Preparation of Compound G-19

The operating steps are the same as in Example 1, except that the ferrocene substrate used is: 1-dimethylaminomethyl-1'-methylruthenium (30.2 mg) to obtain compound G-19 (yellow oily liquid , yield 42%). ¹ H NMR (400MHz, CDCl ₃ ) δ4.76 (dd, J＝2.4, 1.2Hz, 1H), 4.58 (dd, J＝2.5, 1.2Hz, 1H), 4.49 (t, J＝2.4Hz, 1H) ,4.43(q,J＝2.0Hz,1H),4.41(q,J＝2.0Hz,1H),4.37(t,J＝1.7Hz,2H),3.16(d,J＝13.2Hz,1H),3.12 (d, J=13.2Hz, 1H), 2.28 (s, 6H), 1.85 (s, 3H); ¹³ C NMR (100MHz, CDCl ₃ ) δ88.6,78.2,75.6,75.0,72.4,72.3,72.0, 71.8,58.4,45.3,43.4,13.5; HRMS(ESI+FTMS):calc'dforC ₁₄ H ₁₉ INRu ⁺ [M+H ⁺ ]429.9600, found 429.9598; HPLC: 96%ee, Daicel Chiralpak OD-Hcolumn, Hexanes/ IPA/Et ₂ NH = 99/1/0.1, 0.7 mL/min, λ = 254 nm, t _R (major) = 8.60 min, t _R (minor) = 7.51 min; -12.06(c 0.15,CHCl ₃ ).

Example 20: Preparation of Compound G-20

The operating steps are the same as in Example 1, except that the ferrocene substrate used is: 1-dimethylaminomethyl-1′-(4,4,5,5-tetramethyl-1,3-dioxo Cyclopent-2-yl)ruthenium (41.7 mg) was used to obtain compound G-20 (yellow oily liquid, yield 32%). ¹ H NMR (400MHz, CDCl ₃ ): δ5.60 (s, 1H), 4.86-4.81 (m, 1H), 4.66 (q, J = 1.5Hz, 1H), 4.64-4.61 (m, 1H), 4.59 (d,J＝1.8Hz,1H),4.54(t,J＝2.4Hz,1H),4.51(t,J＝1.7Hz,2H),3.24(d,J＝13.3Hz,1H),3.19(d ,J＝13.3Hz,1H),2.27(s,6H),1.23(s,12H); ¹³ C NMR (100MHz, CDCl ₃ ): δ97.8,91.4,89.6,82.5,82.4,78.6,74.1,73.5 ,73.3,72.5,71.9,58.3,45.3,42.7,24.4,24.3,22.2,22.2; HRMS(ESI+FTMS):calc'd for C ₂₀ H ₂₉ INO ₂ Ru ⁺ [M+H ⁺ ]544.0281, found544. 0273; HPLC: 98%ee, Daicel Chiralpak IE column, Hexanes/IPA/Et ₂ NH＝99/1/0.1, 0.7mL/min, λ＝254nm, t _R (major)＝15.11min, t _R (minor) =16.86min; 19.80 (c 0.30, CHCl ₃ ).

Example 21: Gram-level preparation of compound G-1

Place a stirrer of appropriate size into a dry 250mL Schlenk bottle, then add palladium acetate (112.3mg, 0.5mmol, 0.1equiv), N-(tert-butoxycarbonyl)-L-valine (325.9mg, 1.5 mmol, 0.3 equiv), potassium carbonate (4.15 g, 30.0 mmol, 6.0 equiv), exhaust and ventilate three times through a double row tube, then add dry N,N-dimethylformamide (45.0 mL) and dry dimethyl formamide Methyl sulfoxide (5.0mL), 2,2,2-trifluoromethyl-1-(2-iodo-3-methyl)phenylethanone (4.71g, 15.0mmol, 3.0equiv), N,N -Dimethylaminomethylferrocene (1.22g, 5.0mmol, 1.0equiv), then the reaction system was stirred at 80°C for 36 hours, then cooled to room temperature, and saturated sodium carbonate solution was added to the reaction system Quench the reaction and extract three times with ethyl acetate. Combine the organic phases and wash them three times with saturated brine. The organic phase is dried over anhydrous sodium sulfate. After filtration, the solvent is removed under reduced pressure and the product is obtained by column chromatography separation. G-1 (1.014g, red oily liquid, yield 55%, 98%ee).

Application Example 1: Preparation of Compound I-1

Place a stirring bar of appropriate size into a dry 10 mL Schlenk tube, add G-1 (36.9 mg, 0.1 mmol, 1.0 equiv), ventilate through the double row tube three times, add 1.5 mL of dry ether, and The reaction system was placed at -40°C, and then n-butyllithium (60 μL, 2.5 M in hexane, 0.15 mmol, 1.5 equiv) was added dropwise to the reaction system. After the dropwise addition was completed, the reaction system was stirred at this temperature for 2 hours. Afterwards, the reaction system was cooled to -78°C, and a solution of p-toluene disulfide (61.6 mg, 0.25 mmol, 2.5 equiv) in diethyl ether (0.5 mL) was added dropwise. After the dropwise addition was completed, the reaction system was stirred at this temperature for 10 minutes, and then the temperature was raised to Stir overnight at room temperature. After the reaction, add water to the reaction system to quench, extract with ethyl acetate three times (10 mL × 3), combine the organic layers and wash with saturated sodium chloride solution, dry over anhydrous sodium sulfate, filter, and remove under reduced pressure. Solvent, product I-1 (yellow oily liquid, yield 62%) can be obtained through column chromatography separation. ¹ H NMR (400MHz, CDCl ₃ ): δ7.04 (d, J = 8.1 Hz, 2H), 6.97 (d, J = 8.0 Hz, 2H), 4.53-4.48 (m, 1H), 4.46 (t, J =1.9Hz,1H),4.31(t,J＝2.6Hz,1H),4.17(s,5H),3.47(d,J＝13.2Hz,1H),3.43(d,J＝13.2Hz,1H), 2.25(s,3H),2.05(s,6H); ¹³ C NMR (100MHz, CDCl ₃ ): δ135.6,133.8,128.4,125.8,86.5,76.3,74.6,70.3,69.4,68.1,55.9,44.3,20.0; HRMS(ESI+FTMS):calc'd for C ₂₀ H ₂₄ FeNS ⁺ [M+H ⁺ ]366.0973, found 366.0976; HPLC: 97%ee, Daicel Chiralpak AD column, Hexanes/IPA/Et ₂ NH＝98/2 /0.1,1mL/min, λ=254nm, _{t R} (major)=5.75min, t _R (minor)=9.35min; 38.13(c0.15,CHCl ₃ ).

Application Example 2: Preparation of Compound I-2

The operating steps were the same as Application Example 1, except that the electrophile used was: diphenylphosphorus chloride (45 μL) to obtain compound I-2 (red solid, yield 65%). ¹ H NMR (400MHz, CDCl ₃ ): δ7.63-7.55(m,2H),7.38(dq,J=5.6,2.2,1.8Hz,3H),7.26-7.17(m,5H),4.58-4.51( m,1H),4.31(t,J＝2.5Hz,1H),3.93(s,5H),3.90-3.84(m,1H),3.60(dd,J＝13.0,2.5Hz,1H),3.44(d , J=13.1Hz, 1H), 2.00 (s, 6H); ¹³ C NMR (100MHz, CDCl ₃ ): δ140.2 (d, J=8.7Hz), 138.2 (d, J=8.2Hz), 135.1 ( d,J＝21.6Hz),132.6(d,J＝18.2Hz),129.1,128.2(d,J＝7.9Hz),127.9(d,J＝6.2Hz),127.7,90.6(d,J＝25.8Hz ), 76.4 (d, J = 8.8 Hz), 72.8 ( d, J = 4.1 Hz), 71.6 ( d, J = 4.5 Hz), 69.8, 58.0 ( d, J = 9.2 Hz), 45.1; ³¹ P NMR ( 162MHz, CDCl ₃ ): δ-24.5; HRMS (ESI+FTMS): calc'd forC ₂₅ H ₂₇ FeNP ⁺ [M+H ⁺ ]428.1225, found 428.1222; Melting point: 101-102℃; HPLC: 98%ee ,Daicel Chiralpak IG column, Hexanes/IPA/Et ₂ NH＝99/1/0.1, 1mL/min, λ＝254nm, t _R (major)＝11.48min, t _R (minor)＝8.90min; 256.54(c 0.54, CHCl ₃ ).

Application Example 3: Preparation of Compound I-3

The operating steps were the same as Application Example 1, except that the electrophile used was: benzophenone (45.6 mg) to obtain compound I-3 (yellow oily liquid, yield 45%). ¹ H NMR (400MHz, CDCl ₃ ): δ7.63-7.50 (m, 2H), 7.34 (t, J = 7.6Hz, 2H), 7.24 (d, J = 7.3Hz, 1H), 7.21-7.08 (m ,5H),4.07(d,J＝2.3Hz,2H),3.97(s,5H),3.81(t,J＝2.1Hz,1H),3.67(d,J＝13.3Hz,1H),2.68(d , J=13.2Hz, 1H), 1.99 (s, 6H); ¹³ C NMR (100MHz, CDCl ₃ ): δ150.0,147.5,127.5,127.3(2),127.1,126.4,126.3,96.3,82.1,77.6,70.7 ,70.5,69.8,65.4,59.1,44.3; HRMS(ESI+FTMS):calc'd for C ₂₆ H ₂₈ FeNO ⁺ [M+H ⁺ ]426.1515, found 426.1508; HPLC: 98%ee, Daicel Chiralpak AD column, Hexanes/IPA/Et ₂ NH=98/2/0.1, 1mL/min, λ=220nm, _tR (major)=4.30min, _tR (minor)=6.39min; 121.90 (c 0.23, CHCl ₃ ).

Application Example 4: Preparation of Compound I-4

The operating steps were the same as Application Example 1, except that the electrophile used was: trimethylchlorosilane (32 μL) to obtain compound I-4 (red oily liquid, yield 67%). ¹ H NMR (400MHz, CDCl ₃ ): δ4.34-4.28 (m, 1H), 4.24 (t, J = 2.4Hz, 1H), 4.08 (s, 5H), 4.04-3.99 (m, 1H), 3.42 (d, J＝12.5Hz, 1H), 3.01 (d, J＝12.5Hz, 1H), 2.11 (s, 6H), 0.28 (s, 9H); ¹³ C NMR (100MHz, CDCl ₃ ): δ89.2 ,73.3,72.6,71.2,68.7,67.9,58.7,44.1,-0.5; HRMS(ESI+FTMS):calc'd for C ₁₆ H ₂₆ FeNSi ⁺ [M+H ⁺ ]316.1178, found 316.1177; HPLC: 90% ee, Daicel Chiralpak AD column, Hexanes/Et ₂ NH＝100/0.1, 0.5mL/min, λ＝254nm, t _R (major)＝8.47min, t _R (minor)＝9.56min; -24.95(c 0.99,CHCl ₃ ).

Application Example 5: Preparation of Compound J-1

Place a stirring bar of appropriate size into a dry 10 mL Schlenk tube, add I-4 (31.6 mg, 0.1 mmol, 1.0 equiv), ventilate through the double row tube three times, add 1.5 mL of dry ether, and The reaction system was placed at -40°C, and then n-butyllithium (60 μL, 2.5 M in hexane, 0.15 mmol, 1.5 equiv) was added dropwise to the reaction system. After the dropwise addition was completed, the reaction system was stirred at this temperature for 2 hours. Afterwards, the reaction system was cooled to -78°C, and (1R, 2S, 5R)-(-)-menthol (S)-p-toluene sulfinate (69 μL, 0.25 mmol, 2.5 equiv) was added dropwise. After stirring at this temperature for 10 minutes, the temperature was raised to room temperature and stirred overnight. After the reaction, add water to the reaction system to quench, extract with ethyl acetate three times (10 mL × 3), combine the organic layers and wash with saturated sodium chloride solution, dry over anhydrous sodium sulfate, filter, and remove under reduced pressure. Solvent, product J-1 (red oily liquid, yield 51%) can be obtained through column chromatography separation. ¹ H NMR (400MHz, CDCl ₃ ): δ7.66-7.59 (m, 2H), 7.18 (d, J = 8.0Hz, 2H), 4.73 (d, J = 2.6Hz, 1H), 4.35 (s, 5H ),4.19(d,J＝2.6Hz,1H),3.60(d,J＝12.8Hz,1H),3.26(d,J＝12.8Hz,1H),2.33(s,3H),1.92(s,6H ), 0.26 (s, 9H); ¹³ C NMR (100MHz, CDCl ₃ ): δ 144.2, 140.7, 129.4, 125.5, 98.3, 91.7, 74.9, 74.4, 71.0, 66.8, 57.2, 44.5, 21.5, 0.6; HRMS (ESI +FTMS):calc'd for C ₂₃ H ₃₂ FeNOSSi ⁺ [M+H ⁺ ]454.1318, found 454.1320; 221.55(c 0.64, CHCl ₃ ).

Application Example 6: Preparation of Compound M-1

Place a stirring bar of appropriate size into a dry 10 mL Schlenk bottle, and then add palladium acetate (2.2 mg, 0.01 mmol, 0.1 equiv), N-(tert-butoxycarbonyl)-L-valine (6.5 mg, 0.03 mmol, 0.3 equiv) and potassium carbonate (27.6 mg, 0.2 mmol, 2.0 equiv). After ventilating three times through a double row tube, add dry N,N-dimethylformamide DMF (0.4 mL) and dry Dimethyl sulfoxide DMSO (0.1mL), G-1 (36.9mg, 0.1mmol, 1.0equiv), 4-iodotrifluorotoluene (18μL, 0.12mmol, 1.2equiv), 1-n-heptyl-2-nor Bornene (8.3mg, 0.05mmol, 0.5equiv) Then the reaction system was stirred at 80°C for 18 hours. After the reaction was completed, it was cooled to room temperature. A saturated sodium carbonate solution was added to the reaction system to quench the reaction, and extracted three times with ethyl acetate. (10mL Red oily liquid, yield 57%). ¹ H NMR (400MHz, CDCl ₃ ): δ7.52 (s, 4H), 4.98 (d, J = 1.6Hz, 1H), 4.87 (d, J = 1.6Hz, 1H), 4.00 (s, 5H), 3.48 (d, J=13.1Hz, 1H), 3.34 (d, J=13.1Hz, 1H), 2.29 (s, 6H); ¹³ C NMR (100MHz, CDCl ₃ ): δ142.3, 128.5, 128.2, 126.0, 125.6 ,125.6,125.6,125.5,87.0,84.4,73.6,73.5,67.5,58.9,46.9,45.4; HRMS(ESI+FTMS):calc'd for C ₂₀ H ₂₀ F ₃ FeIN ⁺ [M+H ⁺ ]513.9936, found 513.9935; HPLC: 99%ee, DaicelChiralpak OD-H column, Hexanes/IPA/Et ₂ NH＝97/3/0.1, 1mL/min, λ＝254nm, t _R (major)＝9.01min, t _R (minor )=7.36min;/> 31.30(c 0.21, CHCl ₃ ).

The above are only preferred specific embodiments of the present invention, but the scope of protection of the present invention is not limited thereto. Any modifications made by those skilled in the art within the technical scope disclosed in the present invention are equivalent to Substitutions and improvements should be included in the protection scope of the invention.

Claims (10)

1. A method for synthesizing planar chiral iodometallocene, characterized in that it includes the following steps: Under the protection of inert gas, use N,N-dialkylaminomethylferrocene or ruthenium A as the starting material, under the action of iodinated reagent B, palladium catalyst C, chiral amino acid D and base E , stir in organic solvent F until the reaction is completed, and the reaction mixture is extracted, concentrated, and purified by column chromatography to obtain the 1,2-disubstituted planar chiral iodometallocene compound G as in the reaction formula; Among them, the structure of A is: R ¹ and R ² are two independent groups or connected to form one group; if they are independent groups, R ¹ and R ² are selected from C1-C6 alkyl groups; if R ¹ and R ² are connected to form one group , then the group is C1-C7 cycloalkyl, C1-C7 epoxyalkyl, N, S-substituted C1-C7 cycloalkyl; M is iron or ruthenium; R ³ is selected from hydrogen, C6-C12 aryl, N, S substituted C5-C12 heterocyclic aryl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, cyano, C1- C6 aldehyde group, C2-C7 epoxy group, C2-C11 ester group, carboxyl group, amide group, -TMS or The structure of B is: R ⁴ is selected from any one or more of hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C6-C12 aryl, and halogen; The structure of G is: 2. The method for synthesizing planar chiral iodometallocene according to claim 1, characterized in that R ³ includes hydrogen; C1-C6 alkyl; C2-C6 alkenyl; C2-C6 alkynyl; C6 -C12 aryl; C2-C11 ester group is -(CH ₂ ) _x -COOR′, x is an integer from 0 to 4, R′ is C1-C6 alkyl; N, S substituted C5-C12 heterocyclic aryl group include Halogen; cyano group; C1-C6 aldehyde group; acetal includes/> -TMS;/> 3. The method for synthesizing planar chiral iodometallocene according to claim 1, characterized in that the palladium catalyst C is selected from the group consisting of Pd(OAc) ₂ , Pd(PPh ₃ ) ₂ (OAc) ₂ , Pd( TFA) ₂ , Pd(acac) ₂ , Pd(OPiv) ₂ , Pd(PhCN) ₂ Cl ₂ , Pd(MeCN) ₂ Cl ₂ , Pd(PPh ₃ ) ₂ Cl 2 , PdCl ₂ , PdI _{2 ,} [Pd( allyl)Cl] ₂ any one or more. 4. The method for synthesizing planar chiral iodometallocene according to claim 1, characterized in that the structural formula of the chiral amino acid D is: in: i) R ⁵ is selected from any one of benzoyl, acetyl, benzyloxycarbonyl, tert-butoxycarbonyl, ester, C1-C6 alkyl, and benzyl; ii) R ⁶ is selected from any one of C6-C12 aryl or C1-C6 alkyl; In the chiral amino acid D, the ester group in R ⁵ is -COOR", R" is a C1-C6 alkyl group, C6-C12 aryl group; the C6-C12 aryl group in R ⁶ is -(CH ₂ ) _y -Ph, y is an integer from 0 to 4. 5. The method for synthesizing planar chiral iodometallocene according to claim 1, wherein the base E is selected from the group consisting of sodium carbonate, potassium carbonate, cesium carbonate, sodium acetate, potassium acetate, cesium acetate, and potassium phosphate. , any one or more of potassium formate, sodium hydroxide, and sodium tert-butoxide. 6. The method for synthesizing planar chiral iodometallocene according to claim 1, wherein the solvent F is selected from the group consisting of methanol, ethanol, isopropyl alcohol, tert-butyl alcohol, tetrahydrofuran, 2-methyltetrahydrofuran, Diethyl ether, dimethyl ethylene glycol, methyl tert-butyl ether, 1,4-dioxane, 1,3-dioxane, methylene chloride, 1,2-dichloroethane, chloroform, tetrahydrofuran Chlorinated carbon, C4-12 saturated alkanes, C3-12 fluorinated or chlorinated alkanes, benzene, toluene, xylene, trimethylbenzene, dimethyl sulfoxide, N,N-dimethylformamide, N,N - Any one or more of dimethylacetamide, acetone, N-methylpyrrolidone, acetonitrile, and C3-12 saturated alkyl nitriles. 7. The method for synthesizing planar chiral iodometallocene according to claim 1, characterized in that the reaction temperature is 25°C to 120°C. 8. A planar chiral iodometallocene, characterized in that it is prepared by the method described in any one of claims 1-7. 9. A planar chiral iodometallocene prepared by the method of any one of claims 1 to 7 is used to prepare 1,2-disubstituted planar chiral metallocene compounds and 1,2,3-trisubstituted planar chiral metallocene compounds. The method for chiral metallocene compounds is characterized by: (1) Preparation of 1,2-disubstituted planar chiral metallocene compounds, including the following steps: Under the protection of inert gas, use ferrocene iodide or ruthenium G as the starting material, stir in the organic solvent F under the action of electrophile H and base E until the end of the reaction, extract and concentrate the reaction mixture, Purification by column chromatography yields the 1,2-disubstituted planar chiral metallocene compound as I in the reaction formula; The reaction formula is as follows: (2) The preparation method of 1,2,3-trisubstituted planar chiral metallocene compounds, the steps are as follows: Under the protection of an inert gas, use 1,2-disubstituted ferrocene or ruthenium I as the starting material, and under the action of the electrophile H and the base E, stir in the organic solvent F until the end of the reaction. Extraction, concentration, and column chromatography purification yield the 1,2,3-trisubstituted planar chiral metallocene compound as J in the reaction formula; The reaction formula is as follows: In (1) and (2), H and the corresponding group R ⁷ or R ⁸ are expressed as H/corresponding group, selected from: trialkyl chlorosilane/trialkyl silyl, diarylphosphine chloride/ Diarylphosphine, arylformyl chloride/arylformyl, diarylketone/diarylhydroxymethyl, alkyl chloroformate/alkoxyacyl, diaryl chlorophosphate/diaryloxy Phosphono group, diaryl sulfide/diaryl sulfide group; the alkyl group is a C1-C6 alkyl group, and the aryl group is a C6-C12 aryl group. 10. A method for preparing 1,2,4-trisubstituted planar chiral metallocene using the planar chiral iodometallocene prepared by the method of any one of claims 1 to 7, which is characterized in that it includes the following step: Under the protection of inert gas, use ferrocene iodide or ruthenium G and aryl halide K as starting materials, under the action of palladium catalyst C, chiral amino acid D, norbornene derivative L and base E , stir the reaction in organic solvent F until the end of the reaction, filter, concentrate, and purify the reaction mixture by column chromatography to obtain a 1,2,4-trisubstituted planar chiral metallocene compound of formula M; The reaction formula is as follows: in: R ⁹ is selected from C6-C12 aryl, N, S-substituted C5-C12 heterocyclic aryl, C1-C6 alkyl, aldehyde, hydroxyl, amino, cyano, nitro, amide, C1-C6 alkoxy Base, C2-C6 alkenyl, C2-C6 alkynyl, one or more of halogen; X is bromine or iodine; m represents the number of R ⁹ , 0≤m≤3; when m=2 or 3, the substituent groups can be the same or different; Ar ¹ is C6-C12 aromatic hydrocarbons and N, S-substituted C5-C12 heterocyclic aromatic hydrocarbons; The structural formula of norbornene derivative L is: in: i) R ¹⁰ is the substituent on the left five-membered ring, n represents the number of substituents, 0≤n≤8; R ¹¹ is the substituent on the double bond, p represents the number of substituents, 0≤p≤2; ii) R ¹⁰ and R ¹¹ are selected from C6-C12 aryl, N, S-substituted C5-C12 heterocyclic aryl, C1-C6 alkyl, aldehyde, carboxyl, hydroxyl, amino, cyano, nitro, amide Any one or more of base, C1-C6 alkoxy group, C1-C6 alkenyl group, C1-C6 alkynyl group or halogen; iii) When the number of substituents on the left five-membered ring is 2 or more, they may be the same or different; when the number of substituents on the double bond is 2, they may be the same or different; iv) The types of R ¹⁰ and R ¹¹ substituents may be the same or different.