CN111393476B

CN111393476B - Chiral bidentate nitrogen phosphine ligand Rong-Phos and preparation method and application thereof

Info

Publication number: CN111393476B
Application number: CN202010223130.7A
Authority: CN
Inventors: 张俊良; 张荣华; 徐杉
Original assignee: East China Normal University
Current assignee: Anhui Kaitailai Platinum Technology Co ltd
Priority date: 2020-03-26
Filing date: 2020-03-26
Publication date: 2021-11-19
Anticipated expiration: 2040-03-26
Also published as: CN111393476A

Abstract

The invention discloses a new type (1) chiral bidentate nitrogen phosphine ligand Rong-Phos and a preparation method and application thereof. The invention also discloses a chiral bidentate nitrogen phosphine ligand Rong-Phos iridium complex shown in the formula (2) and a nitrogen chiral center high enantioselectivity construction method and application thereof. The iridium complex has both a carbon chiral center and a nitrogen chiral center and is stable in property, the method for constructing the nitrogen atom center of the iridium complex with high enantioselectivity is adopted, a pair of diastereomer catalysts with different nitrogen center chiralities of the iridium complex is applied to asymmetric hydrogenation reaction of cyclic unsaturated carbonyl compounds, and the iridium complex obtains excellent reaction activity and enantioselectivity in asymmetric hydrogenation reaction of other cyclic unsaturated carbonyl compounds, is remarkably excellent in effect, and has scientific research value and wide application prospect.

Description

Chiral bidentate nitrogen phosphine ligand Rong-Phos and preparation method and application thereof

Technical Field

The invention belongs to the technical field of organic chemistry, and particularly relates to a novel chiral bidentate nitrogen phosphine ligand, and preparation and application thereof.

Background

Chirality widely exists in nature, chiral compounds cannot be overlapped with each other just like the left hand and the right hand of people, and two enantiomers are mirror images of each other but cannot be completely overlapped. Two enantiomers that appear to be close, however, often have different optical, physicochemical, and biological activities that are different or even diametrically opposed.

In 2001, the Nobel prize was awarded to Knowles, Noyori and Sharpless for asymmetric catalytic hydrogenation and asymmetric catalytic oxidation studies. Asymmetric hydrogenation is one of the most effective methods for preparing various optically pure compounds because of its high efficiency, atom economy and good industrial application prospects. In particular, a large amount of studies have been made on the preparation of chiral amines, chiral amino acids, chiral alcohols, chiral carboxylic acids, etc., and have been successfully applied industrially. The chiral compounds have important and wide application value, and the asymmetric preparation of the chiral compounds is always a research focus and a hot spot in the field of organic synthesis. Among them, asymmetric catalysis, especially asymmetric hydrogenation, is gradually showing great potential in its industrial production due to its advantages of high efficiency, greenness and economy.

Chiral phosphine Ligands such as SIPHOX are widely used in asymmetric catalytic hydrogenation (C.C.Bausch, A.Pfaltz, Privileged Chiral Ligands and Catalysts (Ed.: Q. -L.Zhou), Wiley-VCH, Weinheim,2011, Chap.6, pp.221-256), such Ligands are used in asymmetric catalytic hydrogenationChiral phosphine nitride, and transition metal complexes can be used as asymmetric catalytic hydrogenation catalyst. The chiral centers commonly used in chiral ligands are carbon, phosphorus, and sulfur chiral centers because they are stable and when sp is³When a hybridized nitrogen atom connects three different groups, the nitrogen atom can also become a chiral center, but the chirality of the nitrogen atom is easy to flip and is unstable, so that the chirality of the nitrogen atom is generally not considered, and therefore the nitrogen atom is not used as the chiral center to design a corresponding chiral ligand. Although some chiral ligands containing nitrogen have been reported, the effect and effect of chirality at the nitrogen center in asymmetric catalytic reactions has not been investigated. We hypothesized whether stable chirality of nitrogen centers can be constructed when a nitrogen atom is coordinated to a metal based on kinetic and thermodynamic stability, to obtain stable metal complexes with nitrogen chiral centers and use them in asymmetric catalytic reactions. This scientific problem opportunity, together with the challenge, deserves our exploration. The subject group has been working on the development of novel C-centered chiral monophosphine ligands (catalysts), leading to the development of Ming-Phos (angelw.chem.int.ed.2014, 53,4350; angelw.chem., int.ed.2016,55,6324; acscataal.2015, 5,7488; acscataal.2017, 7,210), Xiao-Phos (angelw.chem.int.ed.2015, 54,6874), Wei-Phos (angel.chem.int.ed.2015, 54,14853), Peng-Phos (angelw.chem.int.ed.2016, 55,13316), PC-Phos (angelw.chem.chem., int.2017, 56,15905; j.am.chem.soc.2018,140,3467) and N-Phos (angels.chem.2018, 140,3467) and a number of these highly efficient monophosphine ligands (catalysts, many asymmetric catalysts, many of which are available.

Disclosure of Invention

The invention aims to provide a novel chiral bidentate nitrogen phosphine ligand Rong-Phos and a preparation method thereof, a Rong-Phos iridium complex nitrogen chiral center high enantioselectivity preparation method and application thereof in asymmetric catalytic hydrogenation.

The invention provides and synthesizes a new chiral bidentate nitrogen phosphine ligand Rong-Phos, and the ligand has a simple structure, a simple preparation method, a plurality of modifiable sites and a wide application prospect. It is worth mentioning that the Rong-Phos provided by the invention can construct an iridium complex with carbon center chirality and nitrogen center chirality at the same time with high enantioselectivity when being coordinated with transition metal iridium, and the characteristic endows the iridium complex with different activities and different chiral environments in a catalytic process, which cannot be realized by other ligands. The iridium complex contains four isomers in total, and iridium complexes with different stereo structures have different properties and advantages. The invention can accurately control the construction of carbon center chirality and nitrogen center chirality with high enantioselectivity, and applies the iridium complexes to asymmetric catalytic hydrogenation reaction of cyclic unsaturated carbonyl compounds. The iridium complex has only difference of chirality of nitrogen center, but different chiral environments in the catalysis process, products with R configuration and S configuration can be obtained with high enantioselectivity respectively, the iridium complex becomes a successful case for solving the chemical problem of synthesizing a pair of enantiomers by using a ligand with one configuration, and the iridium complex also shows excellent reaction activity and high enantioselectivity in the asymmetric hydrogenation reaction of other cyclic unsaturated carbonyl compounds, and has scientific research value and wide application prospect.

The novel chiral bidentate nitrogen phosphine ligand Rong-Phos and the ionic iridium complex thereof have four configurations because the iridium complex has carbon center chirality and nitrogen center chirality at the same time, and can obtain four optically pure ionic iridium complexes with full configurations at high enantioselectivity.

The chiral bidentate nitrogen phosphine ligand Rong-Phos and the chiral bidentate nitrogen phosphine ligand Rong-Phos iridium complex respectively have structural formulas shown as the following formulas (1) and (2):

in the above (formula 1) or (formula 2): ar is selected from

R¹Selected from hydrogen, C₁～C₁₂Alkyl of (A), C₁～C₁₂Alkoxy group of,

R²、R³Are respectively and independently selected from hydrogen and C₁～C₁₂Alkyl of (A), C₁～C₁₀Siloxane group of (A), C₁～C₁₀Alkanoyl of (2), C₁～C₁₀Ester group of (1), C₁～C₁₀A sulfonate group of,

OR^w、SR^w；R⁴、R⁵Are respectively and independently selected from hydrogen and C₁～C₁₂An alkyl group of,

Wherein R is^xAnd R^x’Are respectively and independently selected from hydrogen, halogen and C₁～C₁₂Alkyl of (A), C₁～C₁₀Alkoxy group of (C)₁～C₁₀Siloxane group of (A), C₁～C₁₀Alkanoyl of (2), C₁～C₁₀Ester group of (1), C₁～C₁₀A sulfonate group of (a); r^y、R^zAnd R^wAre each independently selected from C₁～C₁₂Alkyl of (A), C₁～C₁₀Alkoxy group of (C)₁～C₁₀Siloxane group of (A), C₁～C₁₀Alkanoyl of (2), C₁～C₁₀Ester group of (1), C₁～C₁₀A sulfonate group of (a); n is an integer of 1-5;

x is: BARF^-、BF₄ ^-、PF₆ ^-Or Cl^-An anion of any of (1).

Preferably, Ar in the above (formula 1) or (formula 2) is selected from

R¹Is selected from C₁～C₁₂An alkyl group of,

R²、R³Are respectively and independently selected from hydrogen and C₁～C₁₂Alkyl of (A), C₁～C₁₀Siloxane group of (A), C₁～C₁₀An ester group of,

R⁴、R⁵Are respectively and independently selected from hydrogen and C₁～C₁₂An alkyl group of,

Wherein R is^xAnd R^x’Are respectively and independently selected from hydrogen, halogen and C₁～C₁₂Alkyl of (A), C₁～C₁₀Alkoxy group of (C)₁～C₁₀Siloxane group of (A), C₁～C₁₀Alkanoyl of (2), C₁～C₁₀Ester group of (1), C₁～C₁₀A sulfonate group of (a); n is an integer of 1 to 5.

Further preferably, Ar in the formula (1) or the formula (2) is selected from the group consisting of

R¹Is selected from C₁～C₁₂An alkyl group of,

R²、R³Are respectively and independently selected from hydrogen and C₁～C₁₂An alkyl group of,

Wherein R is^xAnd R^x’Are respectively and independently selected from hydrogen, halogen and C₁～C₁₂And n is an integer of 1 to 5.

In the invention, the compound of the formula (1) is purified by a silica gel column to obtain an optically pure compound shown as a formula (S) -1 and (R) -1;

in the formula:

ar is selected from

OR^w、SR^w；

Wherein R is^xAnd R^x’Are respectively and independently selected from hydrogen, halogen and C₁～C₁₂Alkyl of (A), C₁～C₁₀Alkoxy group of (C)₁～C₁₀Siloxane group of (A), C₁～C₁₀Alkanoyl of (2), C₁～C₁₀Ester group of (1), C₁～C₁₀A sulfonate group of (a);

R^y、R^zand R^wAre each independently selected from C₁～C₁₂Alkyl of (A), C₁～C₁₀Alkoxy group of (C)₁～C₁₀Siloxane group of (A), C₁～C₁₀Alkanoyl of (2), C₁～C₁₀Ester group of (1), C₁～C₁₀A sulfonate group of (a);

n is an integer of 1 to 5.

As a still further preferred embodiment, the chiral bidentate azaphosphine ligand Rong-Phos and Rong-Phos iridium complex is selected from the group consisting of the following compounds;

wherein: ph is phenyl, Ad is 1-adamantyl, Me is methyl, Bn is benzyl, and nBu is n-butyl.

The invention discloses a chiral bidentate nitrogen phosphine ligand Rong-Phos and a high enantioselectivity preparation method of an ionic iridium complex thereof.

The invention provides a synthesis method of a chiral bidentate nitrogen phosphine ligand Rong-Phos, which comprises the following three steps.

The method comprises the following steps: comprises the following first step and second step;

reference is made to the patent granted to this subject group-chiral sulfinamide monophosphine ligand, its full configuration preparation method and application (application number: CN201310671902.3, publication number: CN103709195A) to prepare the chiral sulfinamide monophosphine ligand Ming-Phos described in the present invention, i.e., the compound of formula (3). Then, a nitrogen atom substituted Ming-Phos, namely the compound shown as the formula (4), is generated through a substitution reaction, and then, a hydrolysis reaction is carried out under the action of hydrochloric acid to obtain the chiral bidentate nitrogen phosphine ligand Rong-Phos.

The first step is as follows: starting from a compound of the following formula (3), under the action of a base, and reacting with R⁴Carrying out substitution reaction on the X to obtain a nitrogen atom substituted Ming-Phos compound;

wherein the compound of formula (3) comprises formula (S)_C,R_S) -3, formula (S)_C,S_S) -3, formula (R)_C,S_S) -3, formula (R)_C,R_S)-3；

Wherein the nitrogen atom substituted Ming-Phos compound comprises the formula (S)_C,R_S) -4, formula (S)_C,S_S) -4, formula (R)_C,S_S) -4, formula (R)_C,R_S)-4；

Wherein the base comprises BuLi, NaH, K₂CO₃,Na₂CO₃,KHCO₃,NaHCO₃,KOH,NaOH；

The reaction scheme of the first step is as follows:

wherein, the compound of formula (3), a base and R⁴The molar ratio of X is 1: 0.1-10; the reaction temperature is-78-30 ℃; the reaction time is 0.5 to 12 hours. The solvent may be dichloromethane, diethyl ether, dibutyl ether, methyl tert-butyl ether, ethylene glycol dimethyl ether, 1, 4-dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, toluene,One or any mixture of xylene, benzene, chlorobenzene, fluorobenzene, chloroform and n-hexane. The alkali is used for exchanging with halogen X and carrying out substitution reaction in the reaction; the alkali comprises BuLi, NaH, K₂CO₃，Na₂CO₃，KHCO₃，NaHCO₃，KOH，NaOH。

The second step is that: the compound of formula (S)_C,R_S) -4, formula (S)_C,S_S) -4, formula (R)_C,S_S) -4, formula (R)_C,R_S) -4, under the action of hydrochloric acid, carrying out hydrolysis reaction to obtain chiral bidentate phosphine nitride Rong-Phos formula (S) -1 and formula (R) -1;

the reaction formula of the second step is as follows:

wherein the molar ratio of the compound shown in the formula (4) to HCl is 1: 0.1-10; the reaction temperature is 0-30 ℃; the reaction time is 0.5 to 12 hours. The solvent can be one or any mixture of methanol, ethanol, n-butanol, isopropanol, dichloromethane, diethyl ether, dibutyl ether, methyl tert-butyl ether, ethylene glycol dimethyl ether, 1, 4-dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, toluene, xylene, benzene, chlorobenzene, fluorobenzene, chloroform and n-hexane.

The invention also provides another method for preparing the chiral bidentate nitrogen phosphine ligand Rong-Phos, which comprises the following steps:

and in the second method, the Ming-Phos, namely the compound shown as the formula (3), is subjected to hydrolysis reaction under the action of hydrochloric acid to obtain intermediates shown as the formula (A) and the formula (B), and the intermediates are subjected to condensation and reduction with aldehyde without purification to obtain the chiral bidentate nitrogen phosphine ligand Rong-Phos.

The first step is as follows: starting from the compound of formula (3), under the action of hydrochloric acid, hydrolysis reaction occursObtaining intermediates shown in formula (A) and formula (B): wherein the compound of formula (3) comprises formula (S)_C,R_S) -3, formula (S)_C,S_S) -3, formula (R)_C,S_S) -3, formula (R)_C,R_S)-3；

The reaction scheme of the first step is as follows:

wherein the molar ratio of the compound shown in the formula (3) to HCl is 1: 0.1-10; the reaction temperature is 0-30 ℃; the reaction time is 0.5 to 12 hours. The solvent can be one or any mixture of methanol, ethanol, n-butanol, isopropanol, dichloromethane, diethyl ether, dibutyl ether, methyl tert-butyl ether, ethylene glycol dimethyl ether, 1, 4-dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, toluene, xylene, benzene, chlorobenzene, fluorobenzene, chloroform and n-hexane.

The second step is that: the intermediate shown in the formula (A) and the formula (B) is subjected to condensation with aldehyde and reduction by a reducing agent to obtain chiral bidentate phosphine nitride Rong-Phos formula (S) -1 and formula (R) -1;

the reaction formula of the second step is as follows:

wherein, the intermediate

The molar ratio of the aldehyde to the reducing agent is 1: 0.1-10; the reaction temperature is 0-30 ℃; the reaction time is 0.5 to 12 hours. The solvent can be one of methanol, ethanol, n-butanol, isopropanol, dichloromethane, 1, 2-dichloroethane, diethyl ether, dibutyl ether, methyl tert-butyl ether, ethylene glycol dimethyl ether, 1, 4-dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, toluene, xylene, benzene, chlorobenzene, fluorobenzene, chloroform, n-hexane or any mixture thereof. The reducing agentIncluding sodium borohydride, sodium triacetoxyborohydride, borane, lithium aluminum hydride, sodium hydride, DIBAL, potassium borohydride.

and in the third method, starting from Ming-Phos, namely the compound shown in the formula (3), in the second method, hydrolysis reaction is carried out under the action of hydrochloric acid to obtain an intermediate, and the intermediate is subjected to substitution reaction with alkyl halide without purification to obtain the chiral bidentate nitrogen phosphine ligand Rong-Phos.

The first step is as follows: starting from a compound shown in the following formula (3), carrying out hydrolysis reaction under the action of hydrochloric acid to obtain an intermediate shown in the formula (A) and the formula (B); wherein the compound of formula (3) comprises formula (S)_C,R_S) -3, formula (S)_C,S_S) -3, formula (R)_C,S_S) -3, formula (R)_C,R_S)-3；

The reaction scheme of the first step is as follows:

The second step is that: reacting an intermediate shown in a formula (A) and a formula (B) with R under the action of alkali⁴X and R⁵And carrying out substitution reaction on X to obtain a chiral bidentate nitrogen phosphine ligand Rong-Phos formula (S) -1 and a chiral bidentate nitrogen phosphine ligand Rong-Phos formula (R) -1.

The reaction scheme of the second step is as follows:

wherein, the intermediate

R⁴、R⁵The molar ratio of the alkali to the alkali is 1: 0.1-10: 2-20; the reaction temperature is 0-100 ℃; the reaction time is 1 to 24 hours. The solvent can be one of acetonitrile, methanol, ethanol, n-butanol, isopropanol, dichloromethane, diethyl ether, dibutyl ether, methyl tert-butyl ether, ethylene glycol dimethyl ether, 1, 4-dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, toluene, xylene, benzene, chlorobenzene, fluorobenzene, chloroform and n-hexane or any mixture thereof. The base in the reaction can be potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, potassium bicarbonate, sodium bicarbonate, triethylamine, diethylamine, potassium tert-butoxide and sodium tert-butoxide.

The invention also provides application of the chiral bidentate nitrogen phosphine ligand Rong-Phos in preparation of an iridium complex of the chiral bidentate nitrogen phosphine ligand Rong-Phos.

The invention also provides a high enantioselectivity preparation method of the chiral bidentate nitrogen phosphine ligand Rong-Phos and the ionic iridium complex thereof.

The invention provides a synthesis method of a chiral bidentate nitrogen phosphine ligand Rong-Phos iridium complex, namely a method for constructing a nitrogen chiral center high enantioselectivity of the chiral bidentate nitrogen phosphine ligand Rong-Phos iridium complex shown in a formula (2), which starts from a compound shown in a formula (1) and [ Ir (COD) Cl]₂Dissolving the sodium salt and the sodium salt in a solvent, and stirring for reaction to prepare an optically pure Rong-Phos iridium complex shown in the formula (2); wherein the compound of formula (1) is as follows; the compound of the formula (1) is a compound of formula (S) -1 or formula (R) -1;

the Rong-Phos iridium complex of formula (2) comprises formula (S)_C,R_N)-2、(S_C,S_N)-2、(R_C,S_N)-2、(R_C,R_N) -2 in four configurations:

the synthesis method of the chiral bidentate nitrogen phosphine ligand Rong-Phos iridium complex comprises the following three methods:

the method comprises the following steps: the compound (S) -1 or (R) -1 is reacted with [ Ir (COD) Cl]₂Reacting, adding H after the reaction is completed₂O and NaX to respectively obtain a chiral bidentate nitrogen phosphine ligand Rong-Phos iridium complex with a single configuration, and a larger group R on a chiral carbon atom²And a larger group R on the nitrogen atom⁴In trans form, having the configuration of formula (S)_C,R_N) -2 and formula (R)_C,S_N) -2; the reaction formula is shown below.

Wherein, the compound of formula (1) and [ Ir (COD) Cl]₂、H₂The molar ratio of O to NaX is 1: 0.1-10: 100-1000: 0.1-10; the reaction temperature is 0-100 ℃; the reaction time is 0.5 to 12 hours. The solvent can be one of dichloromethane, diethyl ether, dibutyl ether, methyl tert-butyl ether, ethylene glycol dimethyl ether, 1, 4-dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, toluene, xylene, benzene, chlorobenzene, fluorobenzene, chloroform and n-hexane or any mixture thereof. NaX can be NaBARF or NaBF in the reaction₄、NaPF₆、NaCl。

The second method comprises the following steps: the compound (S) -1 or (R) -1, [ Ir (COD) Cl]₂And NaX react together to respectively obtain a Rong-Phos iridium complex with a single configuration and a larger group R on a chiral carbon atom²And a larger group R on the nitrogen atom⁴Is in cis form and has the configuration as formula (S)_C,S_N) -2 and formula (R)_C,R_N) -2.

Wherein, the compound of formula (1) and [ Ir (COD) Cl]₂The molar ratio of NaX to NaX is 1: 0.1-10; the reaction temperature is 0-100 ℃; the reaction time is 0.5 to 12 hours. The solvent can be one of dichloromethane, diethyl ether, dibutyl ether, methyl tert-butyl ether, ethylene glycol dimethyl ether, 1, 4-dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, toluene, xylene, benzene, chlorobenzene, fluorobenzene, chloroform and n-hexane or any mixture thereof. NaX can be NaBARF or NaBF in the reaction₄、NaPF₆、NaCl。

The third method comprises the following steps: Ming-Phos, i.e. a compound of formula (4) substituted by the nitrogen atom in the Rong-Phos preparation method, [ Ir (COD) Cl]₂Reacting with NaX, and simultaneously obtaining two nitrogen chiral catalysts while keeping the carbon chiral center of Rong-Phos unchanged, and simultaneously obtaining two configurations, namely a Rong-Phos iridium complex of a pair of diastereoisomers; the compound of the formula (4) is a compound of formula (Sc, Rs) -4, (Sc, Ss) -4, (Rc, Rs) -4.

Wherein, the compound of formula (4) < CHEM > and [ Ir (COD) Cl]₂The molar ratio of NaX to NaX is 1: 0.1-10; the reaction temperature is 0-100 ℃; the reaction time is 0.5 to 12 hours. The solvent can be one of dichloromethane, diethyl ether, dibutyl ether, methyl tert-butyl ether, ethylene glycol dimethyl ether, 1, 4-dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, toluene, xylene, benzene, chlorobenzene, fluorobenzene, chloroform and n-hexane or any mixture thereof. NaX can be NaBARF or NaBF in the reaction₄、NaPF₆、NaCl。

In the above method of the invention, the sodium salt is NaBARF or NaBF₄、NaPF₆Or NaCl, wherein the solvent is dichloromethane, and the stirring reaction is as follows: under the inert gas atmosphere, at 0-50 DEG CStirring for 0.5-12 hours at the temperature range.

The chiral bidentate azaphosphine ligand Rong-Phos has a chiral factor: carbon-centered chirality, all with two optical isomers. The Rong-Phos iridium complex has two chiral factors: carbon-centered chirality and nitrogen-centered chirality, all of which have four optical isomers, including two pairs of enantiomers, i.e., carbon-centered chirality is R, nitrogen-centered chirality is R and carbon-centered chirality is S, nitrogen-centered chirality S is a pair of enantiomers; the chirality of the carbon center is S, the chirality of the nitrogen center is R, the chirality of the carbon center is R, and the chirality of the nitrogen center is S, which is the other pair of enantiomers. Therefore, the Rong-Phos iridium complex of the present invention actually contains the above four isomers. These isomers have the same chemical structural formula, but have different steric structures and optical rotation properties.

The invention also provides application of the Rong-Phos iridium complex in asymmetric catalytic hydrogenation of cyclic unsaturated carbonyl compounds, wherein the asymmetric hydrogenation of the cyclic unsaturated carbonyl compounds is realized by dissolving the cyclic unsaturated carbonyl compounds in toluene or 1, 2-dichloroethane and performing pressurized reaction in an environment of 1 atm-100 atm.

Preferably, the cyclic unsaturated carbonyl compound and the chiral bidentate phosphorane ligand hong-Phos iridium complex are present in a molar ratio of 0.0005 to 0.05: 1 is dissolved in toluene or 1, 2-dichloroethane, and the hydrogenation reaction of the cyclic unsaturated carbonyl compound is realized under the pressure reaction in the environment of 1 atm-100 atm.

The structure of the cyclic unsaturated carbonyl compound is as follows:

in the formula: x' C, O, NH or NR⁸；R⁷And R⁸Each is one of aryl, alkyl, alkaryl, aralkyl, or substituted derivatives thereof; n is 0,1, 2,3, 4.

The substituted derivative is: carboxylic acid, alkoxy, hydroxy, alkylmercapto, mercapto, or dialkyl:

the pressure reaction is as follows: reacting for 1-120 hours under hydrogen pressure.

In a specific embodiment, experiments prove that the Rong-Phos iridium complex prepared by the invention can obtain 99% of yield in hydrogenation reaction, and the ee value of the product can reach 99%. This result is already the best level for the substrates of the enones and, for the substrates of lactams, the best results obtained at present.

The invention overcomes the technical difficulties existing in the prior art. In the prior art, a method of phosphine on an ortho-position is adopted from chiral alpha-phenylethylamine, and in the method, a substituent on an alpha position of a benzene ring, namely carbon, can only be methyl or has no substituent, so that the technical limitation is large. The substantial technical breakthrough of the method of the invention can synthesize corresponding structures substituted by a plurality of different substituents at the position, and the effect is remarkable and excellent. The invention provides a technical innovation with extremely high difficulty, and no report is found at present.

The present invention also provides an asymmetric hydrogenation reaction of a cyclic unsaturated carbonyl compound by dissolving the cyclic unsaturated carbonyl compound and the iridium complex of formula (2) Rong-Phos as described above in toluene or 1, 2-dichloroethane and subjecting the resultant to a pressurized reaction in an atmosphere of 1atm to 100 atm.

The novel chiral bidentate nitrogen phosphine ligand Rong-Phos in the formula (1) and the ionic iridium complex thereof have carbon chiral centers and nitrogen chiral centers and are stable in properties. The invention also discloses a method for constructing the nitrogen atom center of the iridium complex with high enantioselectivity, and a pair of diastereomer catalysts with different nitrogen center chiralities of the iridium complex are applied to asymmetric hydrogenation of a cyclic unsaturated carbonyl compound, so that a remarkable excellent result is obtained. The invention also discloses a Rong-Phos iridium complex formula (2) which has carbon center chirality and nitrogen center chirality and is prepared by using the ligand with high enantioselectivity and a method thereof. The invention creatively constructs the Rong-Phos iridium complex with a nitrogen chiral center with high enantioselectivity and successfully applies the Rong-Phos iridium complex to the catalysis of the asymmetric hydrogenation reaction of five-membered cyclic unsaturated carbonyl compounds, and the Rong-Phos iridium complex with a pair of diastereoisomers can respectively obtain products with R configuration and S configuration with high enantioselectivity, so that the invention becomes a successful case for solving the chemical problem of synthesizing a pair of enantiomers by using a ligand with one configuration, and the iridium complex also obtains excellent reaction activity and enantioselectivity in the asymmetric hydrogenation reaction of other cyclic unsaturated carbonyl compounds, thereby having scientific research value and wide application prospect.

Detailed Description

The present invention will be described in further detail with reference to the following specific examples, and the procedures, conditions, reagents, experimental methods and the like for carrying out the present invention are general knowledge and common general knowledge in the art except for those specifically mentioned below, and the present invention is not particularly limited thereto.

The following example provides a synthetic scheme for the aforementioned Rong-Phos Compound 1, specifically:

example 1

(S_C,R_S) Synthesis of (E) -6a

Referring to method one, a 50mL dry single neck bottle was charged under helium atmosphere

(1mmol) and dried tetrahydrofuran solvent (10mL), stirred at-40 ℃ for 10 min, and n-butyllithium (1.6eq.,1mL,1.6M) was added dropwise. Stirring was continued for 1 hour, methyl triflate (1.6mmol) was added, thenStirred for 30 minutes. The reaction was then quenched with saturated ammonium chloride solution. Then carrying out liquid separation, extraction, drying, spin-drying of the solvent and column chromatography purification to obtain the product

The yield was 91%. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) δ 7.76-7.69 (m,1H), 7.37-7.21 (m,11H), 7.18-7.11 (m,1H), 7.11-7.04 (m,1H),5.43(d, J ═ 13.6Hz,1H),2.62(s,3H),1.13(s,9H),1.01(s,9H). phosphorus nuclear magnetic spectrum (202MHz, CDCl)₃) δ -16.37 carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 145.99(d, J ═ 24.4Hz),137.31(d, J ═ 10.6Hz),137.08(d, J ═ 2.7Hz),136.99(d, J ═ 3.4Hz),135.39,133.92(d, J ═ 6.9Hz),133.76(d, J ═ 7.1Hz),129.57(d, J ═ 3.6Hz), 128.67-128.43 (m),128.39,127.39,73.23(d, J ═ 28.4Hz),58.93,38.68,32.84(d, J ═ 1.6Hz),28.97(d, J ═ 1.8Hz),24.75 high resolution mass spectrum theoretical data C, c.75₂₈H₃₇NOPS([M+H]⁺) 466.2328, experimental data 466.2328.

Example 2

(S_C,R_S) Synthesis of (E) -6b

For specific operation, reference is made to example 1, starting from

The yield was 86%. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) delta 7.76-7.71 (m,1H), 7.43-7.39 (m,1H), 7.35-7.29 (m,9H), 7.28-7.23 (m,3H),5.47(d, J ═ 13.1Hz,1H),2.84(s,3H), 1.88-1.73 (m,6H), 1.63-1.48 (m,9H),1.08(s,9H), phosphorus nuclear magnetic spectrum (202MHz, CDCl-₃) δ -18.14, carbon nuclear magnetic (126MHz, Chloroform-d) δ 143.89(d, J, 25.9Hz),137.80(d, J, 11.9Hz),137.33(d, J, 12.3Hz),137.15(d, J, 10.8Hz),136.16(d, J, 1.8Hz),134.10(d, J, 20.0Hz),133.45(d, J, 19.0Hz),129.98(d, J, 4.1Hz),128.67,128.51-128.37 (m),128.33,127.14,73.65(d, J, 27.5Hz),58.66,40.68(d, J, 1.6Hz),40.04,30.10(d, J, 1.4Hz),28.62,24.75(d, J, 2.0) theoretical high-resolution C data₃₄H₄₃NOPS([M+H]⁺) 544.2797, experimental data 544.2794.

Example 3

(S_C,R_S) Synthesis of-6 c

For specific operation, reference is made to example 1, starting from

The yield was 76%. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) δ 7.52-7.12 (m,14H),5.23(t, J ═ 10.2Hz,1H),2.64(s,3H), 2.15-2.03 (m,1H), 2.00-1.88 (m,1H), 1.84-1.75 (m,1H), 1.61-1.50 (m,1H), 1.40-1.27 (m,2H), 1.22-0.91 (m,13H), 0.85-0.78 (m,1H), phosphorus nuclear magnetic spectrum (202MHz, CDCl)₃) δ -18.64 carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 145.32(d, J ═ 25.4Hz),137.04(d, J ═ 12.1Hz), 136.80-136.51 (m),135.02,134.53(d, J ═ 20.7Hz),133.57(d, J ═ 18.8Hz),129.16,128.89,128.66-128.32 (m),127.15,126.86(d, J ═ 4.9Hz),70.10(d, J ═ 26.3Hz),58.61,38.51,30.75,29.95, 26.43-26.01 (m),25.33,24.41(d, J ═ 2.7Hz), high resolution mass spectrometry theoretical data C₃₀H₃₈NNaOPS([M+Na]⁺) 514.2304, experimental data 514.2297.

Example 4

(S_C,R_S) Synthesis of-6 d

For specific operation, reference is made to example 1, starting from

The yield was 93%. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) δ 7.52-7.12 (m,14H),5.23(t, J ═ 10.2Hz,1H),2.64(s,3H), 2.15-2.03 (m,1H), 2.00-1.88 (m,1H), 1.84-1.75 (m,1H), 1.61-1.50 (m,1H), 1.40-1.27 (m,2H), 1.22-0.91 (m,13H), 0.85-0.78 (m,1H), phosphorus nuclear magnetic spectrum (202MHz, CDCl)₃) δ -18.64 carbon spectrum nuclear magnetic δ 145.32(d, J-25.4 Hz),137.04(d, J-12.1 Hz), 136.80-136.51 (m),135.02,134.53(d, J-20.7 Hz),133.57(d, J-18.8 Hz),129.16,128.89,128.66-128.32 (m),127.15,126.86(d, J-4.9 Hz),70.10(d, J-26.3 Hz),58.61,3851,30.75,29.95, 26.43-26.01 (m),25.33,24.41(d, J ═ 2.7Hz)₃₁H₄₂NNaOPS([M+Na]⁺) 530.2617, experimental data 530.2602.

Example 5

(S_C,R_S) Synthesis of-6 e

For specific operation, reference is made to example 1, starting from

The yield was 82%. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) δ 7.91-7.86 (m,1H), 7.46-7.40 (m,1H), 7.36-7.21 (m,12H),5.76(d, J ═ 13.4Hz,1H),2.77(d, J ═ 0.9Hz,3H),1.90(dq, J ═ 14.6,7.3Hz,1H), 1.48-1.38 (m,1H),1.16(s,9H),1.08(s,3H),0.91(t, J ═ 7.4Hz,3H),0.80(dq, J ═ 13.9,7.3Hz,1H),0.57(t, J ═ 7.4Hz,3H), phosphorus nuclear magnetic spectrum (202MHz, cl ═ 7.4Hz,3H), phosphorus nuclear magnetic spectrum (202MHz, CDCl ═ 1H), and the like₃) δ -18.44 carbon nuclear magnetic spectroscopy (126MHz, Chloroform-d) δ 144.80(d, J ═ 25.5Hz),137.97(d, J ═ 11.5Hz),137.48(d, J ═ 11.7Hz),137.10(d, J ═ 10.9Hz),136.21(d, J ═ 1.9Hz), 134.06-133.14 (m),130.30(d, J ═ 4.1Hz), 128.92-128.21 (m),127.25,68.85(d, J ═ 27.4Hz),59.12,42.86,31.44(d, J ═ 2.2Hz),29.00(d, J ═ 2.9Hz),28.63,25.13,22.01(d, J ═ 2.2Hz),8.24,7.66, high resolution theoretical data C, mass spectrometry, and others₃₀H₄₀NOPS([M+H]⁺) 516.2460, experimental data 516.2452.

Example 6

(S_C,R_S) Synthesis of-6 f

For specific operation, reference is made to example 1, starting from

The yield was 83%. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) δ 7.99-7.92 (m,1H), 7.44-7.19 (m,13H),5.77(d, J ═ 13.9Hz,1H),2.73(s,3H), 1.66-1.45 (m,6H), 1.24-1.14 (m,9H),0.71(t, J ═ 7.5Hz,9H), phosphorus nuclear magnetic spectrum (202MHz, CDCl)₃) Delta-18.23. carbon spectrum nucleusMagnetic (126MHz, Chloroform-d) δ 144.94(d, J ═ 25.6Hz),138.13(d, J ═ 11.4Hz),137.46(d, J ═ 11.2Hz),136.92(d, J ═ 11.0Hz),136.26(d, J ═ 1.8Hz),133.87(d, J ═ 20.0Hz),133.31(d, J ═ 18.8Hz),130.90(d, J ═ 3.8Hz), 128.93-128.16 (m),127.39,68.88(d, J ═ 27.4Hz),59.16,45.07,32.11(d, J ═ 2.3Hz),27.27(d, J ═ 2.1Hz),25.27,8.86. high resolution theoretical data C of mass spectrum₃₁H₄₂NNaOPS([M+Na]⁺) 530.2617, experimental data 530.2599.

Example 7

(S_C,R_S) Synthesis of-6 g

For specific operation, reference is made to example 1, starting from

The yield was 85%. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) delta 7.55(ddd, J ═ 7.9,4.5,1.3Hz,1H), 7.43-7.37 (m,1H), 7.33-7.29 (m,3H), 7.23-7.14 (m,6H), 7.06-6.98 (m,5H),6.59(s,1H),3.55(s,3H),2.71(s,3H),1.30(s,18H),1.16(s,9H) phosphorus nuclear magnetic spectrum (122MHz, CDCl)₃) Delta-17.86 carbon spectrum nuclear magnetic (126MHz, Chloroform-d) delta 158.14,146.92(d, J ═ 23.6Hz),142.89,137.82(d, J ═ 11.9Hz),136.11(d, J ═ 3.6Hz),136.01,134.92,133.57(d, J ═ 19.7Hz),132.85,128.85,128.71,128.46,128.41,128.38,128.26(d, J ═ 7.1Hz),127.43,64.10,58.57,35.67,32.07,24.00 high resolution mass spectrometry theoretical data C₃₉H₅₁NO₂PS([M+H]⁺) 628.3370; found,628.3373, experimental data 628.3373.

Example 8

Synthesis of (S) -1a

(1mmol) and a methanol solvent (5mL), concentrated hydrochloric acid (5.0eq.) was added dropwise, and the mixture was stirred at room temperature for 1 hour. Then ethyl acetate is used againThe solution is diluted. Then washing with saturated sodium bicarbonate solution, washing with saturated salt solution, extracting, drying, spin-drying solvent and purifying by column chromatography to obtain

The yield was 96%. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) delta 7.62-7.58 (m,1H), 7.44-7.26 (m,10H), 7.23-7.18 (m,1H), 7.17-7.13 (m,1H),4.71(d, J ═ 8.9Hz,1H),1.96(s,3H),1.07(s,9H). phosphorus nuclear magnetic spectrum (202MHz, CDCl)₃) δ -17.95 carbon nuclear magnetic (126MHz, Chloroform-d) δ 147.69(d, J ═ 23.6Hz),137.95(d, J ═ 12.7Hz),137.72(d, J ═ 2.8Hz),137.62(d, J ═ 4.2Hz),134.86(d, J ═ 2.1Hz),133.89(d, J ═ 20.0Hz),133.56(d, J ═ 19.1Hz),128.85,128.64-128.09 (m),127.54(d, J ═ 5.3Hz),126.78,69.20(d, J ═ 23.7Hz),36.12,35.16,27.55(d, J ═ 3.0Hz), high resolution mass spectrometry theoretical data C₂₄H₂₉NP([M+H]⁺) 362.2032, experimental data 362.2037.

Example 9

Synthesis of (S) -1b

Specific operation with reference to example 8, the starting material used was

The yield was 95%. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) delta 7.56-7.49 (m,1H), 7.41-7.24 (m,11H), 7.21-7.17 (m,1H), 7.16-7.11 (m,1H),4.54(d, J ═ 9.0Hz,1H), 1.99-1.92 (m,6H),1.90(s,3H), 1.71-1.52 (m,9H). phosphorus nuclear magnetic spectrum (202MHz, CDCl)₃) δ -17.33, carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 146.66(d, J ═ 23.9Hz),138.15(d, J ═ 12.7Hz),137.78(d, J ═ 13.0Hz),137.51(d, J ═ 11.5Hz),134.72,133.93(d, J ═ 20.0Hz),133.53(d, J ═ 19.1Hz), 128.76-128.15 (m),127.88(d, J ═ 5.3Hz),126.69,70.10(d, J ═ 23.5Hz),39.36(d, J ═ 3.1Hz),37.88,37.12,35.04,28.68₃₀H₃₅NP([M+H]⁺) 440.2502, experimental data 440.2505.

Example 10

Synthesis of (S) -1c

Specific operation with reference to example 8, the starting material used was

The yield was 91%. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) δ 7.52-7.12 (m,14H),5.23(t, J ═ 10.2Hz,1H),2.64(s,3H), 2.15-2.03 (m,1H), 2.00-1.88 (m,1H), 1.84-1.75 (m,1H), 1.61-1.50 (m,1H), 1.40-1.27 (m,2H), 1.22-0.91 (m,4H), 0.85-0.78 (m,1H), phosphorus nuclear magnetic spectrum (202MHz, CDCl)₃) δ -18.64 carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 145.32(d, J ═ 25.4Hz),137.04(d, J ═ 12.1Hz), 136.80-136.51 (m),135.02,134.53(d, J ═ 20.7Hz),133.57(d, J ═ 18.8Hz),129.16,128.89,128.66-128.32 (m),127.15,126.86(d, J ═ 4.9Hz),70.10(d, J ═ 26.3Hz),58.61,38.51,30.75,29.95, 26.43-26.01 (m),24.41(d, J ═ 2.7Hz), high resolution mass spectrometry theoretical data C, J, and C₂₆H₃₁NP([M+H]⁺) 388.2189, experimental data 388.2190.

Example 11

Synthesis of (S) -1d

Specific operation with reference to example 8, the starting material used was

The yield was 90%. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) δ 7.52-7.12 (m,14H),5.23(t, J ═ 10.2Hz,1H),2.64(s,3H), 2.15-2.03 (m,1H), 2.00-1.88 (m,1H), 1.84-1.75 (m,1H), 1.61-1.50 (m,1H), 1.40-1.27 (m,2H), 1.22-0.91 (m,4H), 0.85-0.78 (m,1H), phosphorus nuclear magnetic spectrum (202MHz, CDCl)₃) δ -18.64 carbon spectrum nuclear magnetism δ 145.32(d, J ═ 25.4Hz),137.04(d, J ═ 12.1Hz), 136.80-136.51 (m),135.02,134.53(d, J ═ 20.7Hz),133.57(d, J ═ 18.8Hz),129.16,128.89,128.66-128.32 (m),127.15,126.86(d, J ═ 4.9Hz),70.10(d, J ═ 26.3Hz),58.61,38.51,30.75,29.95, 26.43-26.01 (m),24.41(d, J ═ 2.7Hz), high resolution mass spectrum theoretical data C, d, J ═ 2.7Hz₂₇H₃₅NP([M+H]⁺) 404.2502, experimental data 404.2505.

Example 12

Synthesis of (S) -1e

Specific operation with reference to example 8, the starting material used was

The yield was 93%. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) δ 7.91-7.86 (m,1H), 7.46-7.40 (m,1H), 7.36-7.21 (m,12H),5.76(d, J ═ 13.4Hz,1H),2.77(d, J ═ 0.9Hz,3H),1.90(dq, J ═ 14.6,7.3Hz,1H), 1.48-1.38 (m,1H),1.08(s,3H),0.91(t, J ═ 7.4Hz,3H),0.80(dq, J ═ 13.9,7.3Hz,1H),0.57(t, J ═ 7.4Hz,3H), phosphorus nuclear magnetic spectrum (202MHz, CDCl)₃) δ -18.44 carbon nuclear magnetic spectroscopy (126MHz, Chloroform-d) δ 144.80(d, J ═ 25.5Hz),137.97(d, J ═ 11.5Hz),137.48(d, J ═ 11.7Hz),137.10(d, J ═ 10.9Hz),136.21(d, J ═ 1.9Hz), 134.06-133.14 (m),130.30(d, J ═ 4.1Hz), 128.92-128.21 (m),127.25,68.85(d, J ═ 27.4Hz),59.12,42.86,31.44(d, J ═ 2.2Hz),29.00(d, J ═ 2.9Hz),28.63,22.01(d, J ═ 2.2Hz),8.24,7.66, high resolution theoretical data C₂₆H₃₃NP([M+H]⁺) 390.2345, experimental data 390.2341.

Example 13

Synthesis of (S) -1f

Specific operation with reference to example 8, the starting material used was

The yield was 95%. Hydrogen nuclear magnetic (500MHz, Chloroform-d) delta 7.99-7.92 (m,1H), 7.44-7.19 (m,13H),5.77(d, J ═ 13.9Hz,1H),2.73(s,3H), 1.66-1.45 (m,6H), 0.71(t, J ═ 7.5Hz,9H), phosphorus nuclear magnetic (202MHz, CDCl)₃) δ -18.23 carbon nuclear magnetic spectroscopy (126MHz, Chloroform-d) δ 144.94(d, J ═ 25.6Hz),138.13(d, J ═ 11.4Hz),137.46(d, J ═ 11.2Hz),136.92(d, J ═ 11.0Hz),136.26(d, J ═ 1.8Hz),133.87(d, J ═ 20.0Hz),133.31(d, J ═ 18.8Hz),130.90(d, J ═ 3.8Hz), 128.93-128.16 (m),127.39,68.88(d, J ═ 27.4Hz),59.16,45.07,32.11(d, J ═ 2.3Hz),27.27(d, J ═ 25 ═ 128.16(m)2.1Hz),8.86. high resolution Mass Spectrometry theoretical data C₂₇H₃₅NP([M+H]⁺) 404.2502, experimental data 404.2502.

Example 14

Synthesis of (S) -1g

Specific operation with reference to example 8, the starting material used was

The yield was 88%. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) delta 7.68-7.63 (m,1H), 7.42-7.23 (m,11H), 7.18-7.11 (m,3H), 7.00-6.94 (m,1H),5.70(d, J ═ 7.9Hz,1H),3.84(s,1H),3.62(s,3H),2.32(s,3H),1.36(s,18H). phosphorus nuclear magnetic spectrum (202MHz, CDCl)₃) Delta-17.63 carbon spectrum nuclear magnetic (126MHz, Chloroform-d) delta 158.03,149.00(d, J ═ 23.3Hz),142.93,137.80(d, J ═ 11.2Hz),136.81,136.72,135.43(d, J ═ 13.2Hz), 134.33-134.26 (m), 134.02-133.43 (m),129.40,128.65-128.25 (m),127.42(d, J ═ 5.4Hz),126.96,126.02(d, J ═ 2.1Hz),65.61(d, J ═ 24.2Hz),64.05,35.70,35.05,32.12 high resolution theoretical data C, mass spectrum₃₅H₄₃NOP([M+H]⁺) 524.3077, experimental data 524.3085.

Example 15

Synthesis of (S) -1b

Referring to method two, a 50mL dry single neck bottle was charged under helium atmosphere

(1mmol) and a methanol solvent (5mL), concentrated hydrochloric acid (5.0eq.) was added dropwise, and the mixture was stirred at room temperature for 1 hour. The solution was then diluted with ethyl acetate. Then washing with saturated sodium bicarbonate solution, washing with saturated salt water, extracting, drying and spin-drying the solvent to obtain a hydrolysis crude product. The crude product and dry 1, 2-dichloroethane (5mL), paraformaldehyde (1.5eq.), and sodium triacetoxyborohydride (3.0eq.) and dry 1, 2-dichlorohydride (3.0eq.) were added under a helium atmosphere in a 50mL dry single neck flaskEthane solution (5 mL). Stirring at room temperature for 12 hours, then filtering, spin-drying the solvent, and purifying by column chromatography to obtain

The yield was 81%. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) delta 7.56-7.49 (m,1H), 7.41-7.24 (m,11H), 7.21-7.17 (m,1H), 7.16-7.11 (m,1H),4.54(d, J ═ 9.0Hz,1H), 1.99-1.92 (m,6H),1.90(s,3H), 1.71-1.52 (m,9H). phosphorus nuclear magnetic spectrum (202MHz, CDCl)₃) δ -17.33 carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 146.66(d, J ═ 23.9Hz),138.15(d, J ═ 12.7Hz),137.78(d, J ═ 13.0Hz),137.51(d, J ═ 11.5Hz),134.72,133.93(d, J ═ 20.0Hz),133.53(d, J ═ 19.1Hz), 128.76-128.15 (m),127.88(d, J ═ 5.3Hz),126.69,70.10(d, J ═ 23.5Hz),39.36(d, J ═ 3.1Hz),37.88,37.12,35.04,28.68₃₀H₃₅NP([M+H]⁺) 440.2502, experimental data 440.2505.

Example 16

Synthesis of (S) -1g

Referring to example 15, the starting material used was n-butyraldehyde in a yield of 78%. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) delta 7.64-7.49 (m,1H), 7.41-7.22 (m,11H), 7.16-7.11 (m,2H),4.74(d, J ═ 9.0Hz,1H), 1.99-0.62 (m,24H), phosphorus nuclear magnetic spectrum (202MHz, CDCl)₃) δ -17.94 carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 146.66(d, J ═ 23.9Hz),138.15(d, J ═ 12.7Hz),137.78(d, J ═ 13.0Hz),137.51(d, J ═ 11.5Hz),134.72,133.93(d, J ═ 20.0Hz),133.53(d, J ═ 19.1Hz), 128.76-128.15 (m),127.88(d, J ═ 5.3Hz),126.69,70.10(d, J ═ 23.5Hz),50.81,39.36(d, J ═ 3.1Hz),37.88,37.12,35.04,28.68,20.1013.18, high resolution mass spectrum theoretical data C₃₃H₄₁NP([M+H]⁺) 482.2971, experimental data 482.2977.

Example 17

Synthesis of (S) -1h

In specific operation with reference to example 15, benzaldehyde was used as the starting material in a yield of83 percent. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) δ 7.75-7.62 (m,1H), 7.49-7.10 (m,18H),4.71(d, J ═ 8.6Hz,1H),3.23(d, J ═ 13.2Hz,1H),3.01(d, J ═ 13.2Hz,1H), 2.04-1.91 (m,6H), 1.70-1.56 (m,9H). phosphorus nuclear magnetic spectrum (202MHz, CDCl)₃) δ -17.03 carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 147.29(d, J ═ 23.8Hz),141.50,138.27-137.53 (m),134.61(d, J ═ 1.9Hz),134.05(d, J ═ 20.1Hz),133.54(d, J ═ 19.1Hz), 128.79-127.69 (m),126.60(d, J ═ 15.4Hz),68.18(d, J ═ 23.2Hz),52.13,39.37(d, J ═ 3.0Hz),38.07,37.17,28.72, high resolution mass spectrometry theoretical data C₃₆H₃₉NP([M+H]⁺) 516.2815, experimental data 516.2817.

Example 18

Synthesis of (S) -1b

Reference method three, adding to a 50mL dry single-neck bottle under helium atmosphere

(1mmol) and a methanol solvent (5mL), concentrated hydrochloric acid (5.0eq.) was added dropwise, and the mixture was stirred at room temperature for 1 hour. The solution was then diluted with ethyl acetate. Then washing with saturated sodium bicarbonate solution, washing with saturated salt water, extracting, drying and spin-drying the solvent to obtain a hydrolysis crude product. The crude product and dry acetonitrile (5mL), methyl iodide (1.5eq), and potassium carbonate (3.0eq.) were added under a helium atmosphere in a 50mL dry single-neck flask. Stirring at 80 deg.C for 12 hr, suction filtering, spin drying solvent, and purifying by column chromatography to obtain

The yield was 82%. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) delta 7.56-7.49 (m,1H), 7.41-7.24 (m,11H), 7.21-7.17 (m,1H), 7.16-7.11 (m,1H),4.54(d, J ═ 9.0Hz,1H), 1.99-1.92 (m,6H),1.90(s,3H), 1.71-1.52 (m,9H). phosphorus nuclear magnetic spectrum (202MHz, CDCl)₃) δ -17.33 carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 146.66(d, J ═ 23.9Hz),138.15(d, J ═ 12.7Hz),137.78(d, J ═ 13.0Hz),137.51(d, J ═ 11.5Hz),134.72,133.93(d, J ═ 20.0Hz),133.53(d, J ═ 19.1Hz), 128.76-128.15 (m),127.88(d, J ═ 5.3Hz),126.69,70.10(d, J ═ 23.5Hz),39.36(d, J ═ 3.1Hz),37.88,37.12,35.04,28.68₃₀H₃₅NP([M+H]⁺) 440.2502, experimental data 440.2505.

Example 19

Synthesis of (S) -1g

Referring to example 18, the starting material used was iodobutane, which was obtained in 82% yield. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) delta 7.64-7.49 (m,1H), 7.41-7.22 (m,11H), 7.16-7.11 (m,2H),4.74(d, J ═ 9.0Hz,1H), 1.99-0.62 (m,24H), phosphorus nuclear magnetic spectrum (202MHz, CDCl)₃) δ -17.94 carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 146.66(d, J ═ 23.9Hz),138.15(d, J ═ 12.7Hz),137.78(d, J ═ 13.0Hz),137.51(d, J ═ 11.5Hz),134.72,133.93(d, J ═ 20.0Hz),133.53(d, J ═ 19.1Hz), 128.76-128.15 (m),127.88(d, J ═ 5.3Hz),126.69,70.10(d, J ═ 23.5Hz),50.81,39.36(d, J ═ 3.1Hz),37.88,37.12,35.04,28.68,20.1013.18, high resolution mass spectrum theoretical data C₃₃H₄₁NP([M+H]⁺) 482.2971, experimental data 482.2977.

Example 20

Synthesis of (S) -1h

Referring to example 18, the starting material used was benzyl bromide in 81% yield. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) δ 7.75-7.62 (m,1H), 7.49-7.10 (m,18H),4.71(d, J ═ 8.6Hz,1H),3.23(d, J ═ 13.2Hz,1H),3.01(d, J ═ 13.2Hz,1H), 2.04-1.91 (m,6H), 1.70-1.56 (m,9H). phosphorus nuclear magnetic spectrum (202MHz, CDCl)₃) δ -17.03 carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 147.29(d, J ═ 23.8Hz),141.50,138.27-137.53 (m),134.61(d, J ═ 1.9Hz),134.05(d, J ═ 20.1Hz),133.54(d, J ═ 19.1Hz), 128.79-127.69 (m),126.60(d, J ═ 15.4Hz),68.18(d, J ═ 23.2Hz),52.13,39.37(d, J ═ 3.0Hz),38.07,37.17,28.72, high resolution mass spectrometry theoretical data C₃₆H₃₉NP([M+H]⁺) 516.2815, experimental data 516.2817.

The following example provides a synthetic scheme for the Rong-Phos iridium complex 2 with different stereo structures, specifically:

example 21

(S_C,R_N) Synthesis of (E) -2a

Reference method one, in a 50mL dry Schlenk reaction flask, add under helium atmosphere

(0.5mmol)、[Ir(COD)Cl]₂(0.25mmol) and dry dichloromethane solvent (10mL) were stirred at 50 ℃ for 6 hours, TLC was sampled and heating was stopped when ligand was completely complexed and the system was allowed to cool to room temperature naturally. Adding H under vigorous stirring₂O (5mL) and NaBARF (661mg) were added and the reaction was continued for 1 hour. Then separating the organic phase with Na₂SO₄Drying, spin-drying solvent, and purifying by column chromatography to obtain

The yield was 80%. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) δ 8.09-7.98 (m,2H), 7.79-7.71 (m,8H), 7.64-7.42 (m,13H), 7.24-7.19 (m,1H), 7.18-7.11 (m,2H), 4.84-4.76 (m,1H),4.29(d, J ═ 6.5Hz,1H), 4.11-4.01 (m,2H),3.47(H, J ═ 3.4,2.5Hz,2H),2.65(d, J ═ 6.0Hz,3H), 2.51-2.39 (m,1H), 2.33-2.16 (m,3H), 2.07-1.99 (m,1H), 1.95-1.83 (m,2H), 1.81-1.70 (m,1H), 1.202H, 9-1H, 9H, 1 cl), 1H, 2H, 1H, p (cl), p, cl, p, c, p₃) δ 5.39. carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 162.38-161.05 (m),139.52(d, J15.4 Hz),136.30,135.12(d, J10.0 Hz),134.93,134.81(d, J4.4 Hz),132.53(d, J9.7 Hz),132.26(d, J2.5 Hz),131.91,131.61(d, J2.3 Hz),131.47,131.29(d, J2.5 Hz),130.56(d, J6.7 Hz),129.43(d, J10.9 Hz), 129.32-129.20 (m), 129.14-128.92 (m), 128.84-128.67 (m), 128.58-128.43 (m),128.32,127.81,125.64,123.47,123.25,122.89,121.30,92.84(d, J8.6 Hz), 5(d, J15.2), 80.01, 3.31 Hz), 75.31 Hz, 31.31 Hz, 3.3.3.3 Hz, 3.3.3 Hz, 3.31 Hz), 75-75 Hz, 31.7, 3.3.3.3, 3.3, 3.3.3, 3.3Hz, 3, Hz,3₃₂H₄₀NPIr⁺([M-BArF]⁺) 662.25221, experimental data 662.25206.

Example 22

(S_C,R_N) Synthesis of (E) -2b

Specific operation with reference to example 21, starting materials used were

The yield was 85%. Nuclear magnetic spectrum (500MHz, Chloroform-d) δ 8.09-8.01 (m,2H), 7.77-7.73 (m,8H), 7.65-7.41 (m,13H), 7.23-7.11 (m,3H), 4.81-4.73 (m,1H), 4.32-4.23 (m,1H), 4.11-4.02 (m,1H), 3.93-3.88 (m,1H), 3.54-3.46 (m,2H),2.65(d, J ═ 5.9Hz,3H), 2.56-2.44 (m,1H), 2.34-2.17 (m,3H), 2.13-2.07 (m,4H), 2.03-1.89 (m,4H), 1.83-1.73 (m,7H), 1.66-1.58 (m, 58H), phosphorus (cl), CDCl, 2H),1 MHz-1.58 (m,1H), 1H, 58(m, 202H), CDCl₃) δ 4.80. carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 162.46-161.01 (m),138.55(d, J ═ 15.7Hz),136.28,135.17-134.64 (m),132.53(d, J ═ 9.6Hz),132.22(d, J ═ 2.5Hz),131.77,131.57(d, J ═ 2.3Hz),131.33,131.20(d, J ═ 2.4Hz),130.58(d, J ═ 6.6Hz), 129.53-128.39 (m),127.81,125.65,123.48,123.10,121.31,117.79-117.11 (m),91.24(d, J ═ 8.1Hz),81.96(d, J ═ 16.3Hz),81.43(d, J ═ 3.1Hz),66.75,63.90,43.42,41.33, mass spectrum 37.54,36.21,34.23(d, J ═ 4.4Hz),32.84 (d, J ═ 28.84, 60 ═ 2.27.27 Hz), theoretical high-resolution data (d, J ═ 2.26 Hz, J ═ 2.27.27 Hz), and theoretical data (d, J ═ 2.3.3 Hz)₃₈H₄₆NPIr⁺([M-BArF]⁺) 740.29916, experimental data 740.29883.

Example 23

(S_C,R_N) Synthesis of (E) -2c

Specific operation with reference to example 21, starting materials used were

The yield was 87%. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) delta 7.77-7.72 (m,9H), 7.70-7.62 (m,2H), 7.59-7.35 (m,14H), 7.17-7.11 (m,1H) 4.79-4.70 (m,1H), 4.54-4.44 (m,1H), 4.40-4.30 (m,1H), 4.13-4.05 (m,1H), 3.43-3.31 (m,1H), 3.27-3.18 (m,1H),2.57(d, J ═ 6.0Hz,3H), 2.46-2.19 (m,2H), 2.16-1.96 (m,4H), 1.95-1.75 (m,3H), 1.33-1.25 (m,5H), 1.19-0.99 (m,2H), 0.65-0.53 (m,1H), 0.53-0.44 (m,1H), 0.33-0.21 (m,1H), nuclear magnetic phosphorus spectrum (CDCl (202MHz, 1H)₃) δ 5.02 carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 162.46-160.92 (m),140.99(d, J ═ 14.7Hz),135.34(d, J ═ 2.0Hz),134.80,134.21(d, J ═ 10.9Hz),133.75(d, J ═ 10.0Hz),133.28(d, J ═ 11.4Hz),132.13(d, J ═ 2.5Hz), 132.00-131.85 (m),130.84(d, J ═ 7.1Hz), 129.89-128.36 (m),127.80,125.63,123.47,122.76,122.39,121.30,117.81-117.13 (m),94.07(d, J ═ 11.5Hz),90.51(d, J ═ 12.5Hz), 368 (d, J ═ 5.1Hz),69.50,6, 44.92(d, J ═ 2.6), 40.89, 3632 (d, J ═ 19.19 Hz), 28.88.25.25 Hz), 3619 (d, J ═ 25.38 Hz),40.89, 27, 25, 15, 27, 25, 15, 27, 18, 27, 25, 27, 18, 27, 25,3, 18, Hz, 18, Hz, 18₃₄H₄₂NPIr⁺([M-BArF]⁺) 688.26786, experimental data 688.26744.

Example 24

(S_C,R_N) Synthesis of (E) -2d

Specific operation with reference to example 21, starting materials used were

The yield was 82%. Nuclear magnetic resonance (500MHz, Chloroform-d) δ 8.08-8.00 (m,2H), 7.80-7.72 (m,8H), 7.65-7.58 (m,1H), 7.57-7.42 (m,12H), 7.26-7.20 (m,1H), 7.19-7.10 (m,2H), 4.82-4.75 (m,1H), 4.31-4.24 (m,1H),4.12(d, J ═ 2.3Hz,1H), 4.07-3.99 (m,1H), 3.54-3.48 (m,1H), 3.47-3.42 (m,1H),2.67(d, J ═ 6.0Hz,3H), 2.50-2.39 (m,1H), 2.33-2.13 (m,2H),2.84 (m,1H), 3.19H, 3.85 (m,1H), 3.18H, 3H, 3.18H, 3.7.3H, 3.18(m,1H), 2.3H, 3H, 3.3H, 3H, 3.7.3H, 1H, 3H, 1H, 3H, 1H, 2.3H, 1H, 3H, 1H, 3H, 1H, 3H, 2H, 3H, 1H, 3H, 1H, 2H, 1H, 2H, 1H, 3H, 1H, 2H, 1H, 2H, 1H, 2H, 1H, 2H, 1H, 2H, 1H, 2H, 1H, 2H₃) δ 4.93. carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 162.45-160.78 (m),139.38(d, J ═ 15.5Hz),136.35,135.07(d, J ═ 10.1Hz),134.91,134.81,132.59(d, J ═ 9.6Hz),132.26(d, J ═ 2.5Hz),131.99,131.62-131.52 (m),131.26(d, J ═ 2.6Hz),130.53(d, J ═ 6.7Hz), 129.69-1 (m)28.35(m),127.81,125.64,123.48(d, J ═ 2.7Hz),123.13,121.31,117.96-116.94 (m),92.46(d, J ═ 8.3Hz),84.09(d, J ═ 15.7Hz),79.96(d, J ═ 2.8Hz),66.56,63.72,43.65,41.19(d, J ═ 2.3Hz),38.62,33.26(d, J ═ 3.9Hz),31.80,31.51,30.48(d, J ═ 2.6Hz),30.33,30.16,29.71,27.70(d, J ═ 2.8Hz),26.55(d, J ═ 2.9Hz),25.82,23.36,14.00. high resolution mass spectrometry theoretical data c.00₃₅H₄₆NPIr⁺([M-BArF]⁺) 704.29916, experimental data 704.29831.

Example 25

(S_C,R_N) Synthesis of (E) -2e

Specific operation with reference to example 21, starting materials used were

The yield was 89%. Nuclear magnetic spectrum (500MHz, Chloroform-d) delta 8.09-7.98 (m,2H), 7.84-7.70 (m,9H), 7.67-7.42 (m,12H), 7.26-7.13 (m,3H), 4.87-4.78 (m,1H),4.25(s,1H), 4.22-4.16 (m,1H), 4.02-3.92 (m,1H), 3.51-3.36 (m,2H),2.65(d, J ═ 5.5Hz,3H),2.47(m,1H), 2.31-2.13 (m,5H), 2.11-1.94 (m,2H), 1.90-1.78 (m,1H), 1.69-1.34 (m,4H), 1.23-1.14 (m,2H), 1.01-0.84 MHz, 0.162H, 84 cl), 2H, CDCl, 1H, 1MHz, 1H, 2H, phosphorus (cl), c, cl, c, cl, c, H, c, m, c, m, c, H, m, c, m, c₃) δ 5.96 carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 162.41-161.03 (m),139.37(d, J-15.5 Hz),136.41,134.82(t, J-6.3 Hz),132.46(d, J-9.7 Hz),132.20(d, J-2.4 Hz), 131.73-131.05 (m),130.38(d, J-6.6 Hz), 129.88-128.23 (m),127.82,125.65,124.11,123.75,123.48,121.32,117.47(p, J-4.1 Hz),92.47(d, J-8.2 Hz),83.54(d, J-16.1 Hz),75.98(d, J-2.8 Hz),67.04,63.34,43.56,40.85,33.85(d, J-4.3 Hz),32.54, 31.18-29.48 (m), high resolution (d, J-18, J-23.23 Hz), theoretical high resolution (C-11.11 Hz), theoretical data (d, J-1 Hz), theoretical data (C, J-11.11 Hz), theoretical data (d, J-3 Hz), 3.3Hz), 32.54, 31.18-29.48, 27.18, J-18, J-3, 18, 3, h, and high resolution data (d, 3, h, 3,2, 3, h, 2,3, 2,3, 2,3, 2,3, 2,3, h, etc₃₄H₄₄NPIr⁺([M-BArF]⁺) 690.28351, experimental data 690.28350.

Example 26

(S_C,R_N) Synthesis of (E) -2f

Specific operation with reference to example 21, starting materials used were

The yield was 85%. Nuclear magnetic resonance (500MHz, Chloroform-d) δ 8.04-7.96 (m,2H), 7.79-7.72 (m,8H), 7.66-7.60 (m,1H), 7.58-7.46 (m,10H), 7.34-7.29 (m,1H), 7.24-7.16 (m,2H), 4.81-4.72 (m,1H),4.27(d, J ═ 2.2Hz,1H), 4.11-4.05 (m,1H), 4.02-3.94 (m,1H), 3.47-3.37 (m,2H),2.65(d, J ═ 6.0Hz,3H), 2.52-2.42 (m,1H), 2.29-2.13 (m,2H), 2.09-2.00 (m,1H), 1H, 89-6.84H, 1₃) δ 6.11. carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 162.48-160.76 (m),139.78(d, J ═ 15.5Hz),136.53,135.23-134.47 (m),132.48(d, J ═ 9.7Hz),132.20(d, J ═ 2.7Hz),131.76,131.62(d, J ═ 2.3Hz),131.53(d, J ═ 2.3Hz),131.33,130.54(d, J ═ 6.6Hz), 129.50-128.41 (m),127.81,125.64,124.26,123.89,123.48,121.31,117.46(p, J ═ 4.0Hz),92.10(d, J ═ 8.1Hz),82.81(d, J ═ 16.1Hz),76.09(d, J ═ 2.6Hz),66.46,63.69, mass spectrum 43.35,43.14,33.66(d, J ═ 4.2), high resolution (32.44, 30.31.31, 31.31.31, 27.31.31 Hz), theoretical data (d, J ═ 8.6Hz), 66.46,63.69, 27.27.7 Hz), 3.31.7.7 Hz, 27.7, 3, 8, h, and so on₃₅H₄₆NPIr⁺([M-BArF]⁺) 704.29916, experimental data 704.29817.

Example 27

(S_C,R_N) Synthesis of-2 g

Reference method three, in a 50mL dry Schlenk reaction flask, add under helium atmosphere

(0.5mmol)、[Ir(COD)Cl]₂(0.25mmol), NaBARF (661mg) and dry dichloromethane solvent (10mL) were stirred at 50 ℃ for 6h, TLC was sampled and heating was stopped when ligand was completely complexed and the system allowed to cool to room temperature naturally. Then separating the organic phase with Na₂SO₄Drying, spin-drying solvent, and purifying by column chromatography to obtain

The yield was 27%. Nuclear magnetic spectrum (400MHz, Chloroform-d) delta 8.03-7.93 (m,2H), 7.76-7.63 (m,9H), 7.60-7.49 (m,9H), 7.48-7.38 (m,3H), 7.34-7.28 (m,1H), 7.20-7.10 (m,2H),7.04(s,2H),5.51(s,1H),4.45(s,1H),4.29(s,1H),3.73(s,3H), 3.47-3.29 (m,2H), 2.84-2.74 (m,1H),2.49(d, J ═ 6.1Hz,3H), 2.39-2.27 (m,1H), 2.20-1.91 (m,2H), 1.75-1.32 MHz, 23H (cl), 23 MHz, 202 MHz), nuclear magnetic spectrum₃) δ 11.51. carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 162.53-160.68 (m),145.45,141.58(d, J ═ 15.8Hz),135.89,134.95(d, J ═ 12.2Hz),134.78,133.50(d, J ═ 10.3Hz), 132.99-132.32 (m),131.65(d, J ═ 2.5Hz), 130.43-128.22 (m),127.75(d, J ═ 11.7Hz),127.25,126.93,125.63,123.88-123.03 (m),121.29,117.68-35 117.33(m),93.05(d, J ═ 12.5Hz),92.72(d, J ═ 11.5Hz),72.79(d, J ═ 4.1Hz),65.70,64.36,63.25,43.49(d, J ═ 2.0Hz),36.10,32.99(d, J ═ 3.5Hz), 30.84, 29.7 Hz), theoretical high-resolution data (d, J ═ 2.7.7 Hz), theoretical data (d, J ═ 29.7.7 Hz), theoretical data (d, J ═ 2.06.7 Hz), theoretical data (d, J ═ 7.7.7 Hz), 3.7.7 Hz), 3.7Hz, 3.7, 3.5Hz, 3.7, 3₄₃H₅₄NOPIr⁺([M-BArF]⁺) 824.35668, experimental data 824.35675.

Example 28

(S_C,S_N) Synthesis of (E) -2a

Reference method two, in a 50mL dry Schlenk reaction flask, add under helium atmosphere

(0.5mmol)、[Ir(COD)Cl]₂(0.25mmol), NaBARF (661mg) and dry dichloromethane solvent (10mL) were stirred at 50 ℃ for 6 h. Then separating the organic phase with Na₂SO₄Drying, spin-drying solvent, and purifying by column chromatography to obtain

The yield was 74%. Hydrogen nuclear magnetic spectrum (500MHz, Chloroform-d) delta 8.00-7.92 (m,2H), 7.81-7.76 (m,9H), 7.75-7.71 (m,1H), 7.62-7.50(m,11H), 7.35-7.26 (m,3H), 5.02-4.95 (m,1H), 4.60-4.57 (m,1H), 4.33-4.27 (m,1H), 3.97-3.91 (m,1H), 3.47-3.42 (m,1H), 3.26-3.20 (m,1H), 2.50-2.38 (m,2H),2.36(d, J ═ 5.9Hz,3H), 2.29-2.20 (m,1H), 2.15-2.06 (m,1H), 2.05-1.89 (m,3H), 1.78-1.70 (m,1H),1.01(s,9H) phosphorus nuclear magnetic spectrum (202MHz, CDCl)₃) δ 9.35. carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 162.41-161.07 (m),136.90(d, J-11.4 Hz),135.45(d, J-11.8 Hz),134.82,133.38(d, J-10.9 Hz),133.06(d, J-3.7 Hz),132.68(d, J-2.4 Hz),132.05(d, J-2.4 Hz),131.33(d, J-2.2 Hz), 130.04-128.39 (m),128.00,127.83,125.66,124.60,124.16,123.50,121.33,117.64-117.36 (m),93.53(d, J-10.5 Hz),87.10(d, J-13.7 Hz),72.25(d, J-13.3 Hz),69.40,61.19,37.13,35.80,32.19(d, J-3.6), high resolution (d, J-13.55, J-3 Hz), theoretical high resolution (d, J-3.7.7 Hz), 15.8, 7.6, 7.7, 7.6, 7.7.8, 7.6, 7.7, 7.7.6, 7, 7.7, 7,3, 7,3, 7,3, 7,3, 7,3, 7₃₂H₄₀NPIr⁺([M-BArF]⁺) 662.25221, experimental data 662.25231.

Example 29

(S_C,S_N) Synthesis of (E) -2b

Specific operation with reference to example 28, the starting material used was

The yield was 76%. Nuclear magnetic spectrum (500MHz, Chloroform-d) δ 7.98-7.91 (m,2H), 7.86-7.82 (m,1H), 7.76-7.71 (m,9H), 7.65-7.60 (m,1H), 7.59-7.47 (m,11H), 7.28-7.22 (m,2H), 5.03-4.97 (m,1H), 4.33-4.27 (m,2H), 4.13-4.07 (m,1H), 3.43-3.36 (m,1H), 3.20-3.13 (m,1H), 2.47-2.35 (m,2H),2.30(d, J ═ 5.8Hz,3H), 2.26-2.17 (m,1H), 2.12-1.84 (m,7H), 1.76-1H (m, 44H), phosphorus (m, 202 cl), nuclear magnetic spectrum CDCl, 1H), 2H, 2MHz, 2H, 2MHz, 2MHz, 2, 1H, 2, 1H, 2, m,2, 1,2, 1,2, c, 2, c, b, c, b, c, b, c, b, c, b, c, b, c, b, c, b, c₃) δ 9.52. carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 161.72(dd, J ═ 99.5,49.9Hz),136.56(d, J ═ 11.3Hz),135.50(d, J ═ 11.3Hz),134.81,133.68-127.47 (m),125.65,124.61,124.17,123.48,121.32,117.50,93.40(d, J ═ 10.3Hz),86.90(d, J ═ 13.4Hz),73.26(d, J ═ 14.1Hz),69.30,61.07,40.15,38.19,37.67,36.11,32.25(d, J ═ 3.6Hz),31.50,30.50,29.72,29.02,27.91. high resolutionTheoretical data of mass spectrum C₃₈H₄₆NPIr⁺([M-BArF]⁺) 740.29916, experimental data 740.29890.

Example 30

(S_C,S_N) Synthesis of (E) -2c

Specific operation with reference to example 28, the starting material used was

The yield was 83%. Nuclear magnetic spectrum (400MHz, Chloroform-d) δ 7.98(d, J ═ 11.4Hz,1H), 7.74-7.69 (m,11H), 7.54-7.42 (m,12H), 7.34-7.27 (m,1H), 7.24-7.18 (m,1H), 7.13-7.07 (m,1H),4.71(d, J ═ 8.6Hz,1H), 4.59-4.45 (m,2H), 3.64-3.46 (m,2H), 2.75-2.60 (m,1H), 2.40-1.79 (m,7H), 1.71-1.39 (m,5H), 1.32-1.08 (m,6H), 1.02-0.76 (m,3H), phosphorus nuclear magnetic spectrum (CDCl (202MHz, CDCl), 1H), etc₃) δ 6.75 carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 163.21,162.59-160.82 (m),143.45(d, J ═ 14.5Hz),135.65,134.79,133.89(d, J ═ 12.0Hz),132.65(d, J ═ 10.4Hz),132.20(d, J ═ 2.4Hz), 132.05-131.68 (m), 130.80-127.36 (m),125.62,123.46,122.96,122.57,121.29,117.65-117.28 (m),97.54(d, J ═ 10.9Hz),90.94(d, J ═ 12.6Hz),87.33,69.26,67.39,47.11,32.90,32.29(d, J ═ 3.2Hz),31.47(d, J ═ 3.1Hz),31.15,29.99,29.81,25.93(d, J ═ 17.2Hz), high resolution theoretical C data (C51, 25.51 Hz), high resolution data₃₄H₄₂NPIr⁺([M-BArF]⁺) 688.26786, experimental data 688.26757.

Example 31

(S_C,S_N) Synthesis of-2 d

Specific operation with reference to example 28, the starting material used was

The yield was 81%. Hydrogen nuclear magnetic spectrum (400MHz, Chloroform-d) delta 7.97-7.88 (m,2H), 7.76-7.67 (m,10H), 7.58-7.48 (m,11H), 7.30-7.26 (m,1H), 7.23-7.16 (m,2H), 4.94-4.86(m,1H),4.63(s,1H), 4.27-4.16 (m,1H), 3.88-3.78 (m,1H), 3.43-3.35 (m,1H), 3.18-3.10 (m,1H), 2.48-2.32 (m,2H),2.31(d, J ═ 5.9Hz,3H), 2.24-2.13 (m,1H), 2.11-2.00 (m,1H), 2.00-1.87 (m,3H), 1.76-1.64 (m,1H), 1.47-1.15 (m,4H),1.11(s,3H), 1.06-0.91 (m,5H),0.66(t, J ═ 7.3Hz,3H) phosphorus spectra (202MHz, cl, 3 MHz), 3.18(m,1H) and 3H)₃) δ 9.01. carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 162.68-160.60 (m),136.87(d, J ═ 11.3Hz),135.70(d, J ═ 11.6Hz),134.81,133.26(d, J ═ 11.6Hz),132.77,132.04,131.37,130.38-127.06 (m),125.64,124.88,124.43,123.47,121.30,117.46,93.60(d, J ═ 10.5Hz),87.13(d, J ═ 13.5Hz),69.95,69.48,60.99,41.86,38.34,37.34,32.13,31.67,30.67,28.88,26.89,24.69(d, J ═ 22.3Hz),23.02,13.80. high resolution mass spectrometry theory data C, 31.67,30.67,28.88,26.89,24.69(d, J ═ 22.3Hz)₃₅H₄₆NPIr⁺([M-BArF]⁺) 704.29916, experimental data 704.29997.

Example 32

(S_C,S_N) Synthesis of-2 e

Specific operation with reference to example 28, the starting material used was

The yield was 86%. Hydrogen spectrum nuclear magnetism (500MHz, Chloroform-d) delta 8.01-7.93 (m,2H), 7.79-7.72 (m,9H), 7.60-7.50 (m,12H), 7.34-7.29 (m,1H), 7.26-7.20 (m,2H), 4.99-4.91 (m,1H),4.68(s,1H), 4.29-4.20 (m,1H), 3.95-3.88 (m,1H), 3.46-3.38 (m,1H), 3.20-3.10 (m,1H), 2.50-2.31 (m,4H), 2.28-2.16 (m,1H), 2.14-2.03 (m,1H), 2.03-1.89 (m,3H), 1.79-1.68 (m,1H),1.64 (m,1H), 1H, 0.63-0.31H), 1H, 3.31(m,1H), 3.31-2.31 (m,1H), 3.3.3.31-2.18H), 1H, 3.3.3.3.3.3.1H, 3.3.1H, 3.1H, 3, 3.1H, 3H, 3H, 3H, 3, 0.1H, 3H, 3, 1H, 3,1, 0.1, 3,1, 3, 1H, 3, 1H, 3, 0,3, 1,3, 1, 0,1, 3, 0,3, 1,3, 1,2, 3,2, 0,3, 2,3, 1,2, 1,2, 1,2, 1,2, 1,2, 1,2, 3,2, 1,2, 1,2, 1,2, 3,2, 1,2, 1,2, 1,2, 1,2, 1,2₃) δ 8.83. carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 161.70(dd, J ═ 99.7,49.9Hz),136.87(d, J ═ 11.2Hz),135.80(d, J ═ 11.8Hz),134.81,133.31,133.22,132.75(d, J ═ 2.4Hz),132.01(d, J ═ 2.5Hz),131.35,130.22-128.30 (m),127.76(d, J ═ 12.5Hz),127.28,125.64,125.09,124.65,123.47,121.31,117.79-117.16 (m),93.73(d, J ═ 10.4Hz),87.23(d, J ═ 13.6Hz),69.92,69.36(d, J ═ 13.1Hz),60.95,41.25,37.44,32.07(d, J is 3.6Hz),31.68(d, J is 2.8Hz),30.67,30.36,28.86(d, J is 2.6Hz),27.72,21.54,7.02,6.54. high resolution mass spectrometry theoretical data C₃₄H₄₄NPIr⁺([M-BArF]⁺) 690.28351, experimental data 690.28412.

Example 33

(S_C,S_N) Synthesis of (E) -2f

Specific operation with reference to example 28, the starting material used was

The yield was 88%. Hydrogen spectrum nuclear magnetism (500MHz, Chloroform-d) delta 8.02-7.94 (m,2H), 7.84-7.80 (m,1H), 7.79-7.72 (m,9H), 7.63-7.45 (m,9H), 7.36-7.31 (m,1H), 7.27-7.18 (m,2H), 4.99-4.92 (m,1H),4.78(s,1H), 4.30-4.21 (m,1H), 4.00-3.91 (m,1H), 3.48-3.38 (m,1H), 3.14-3.07 (m,1H), 2.54-2.33 (m,5H), 2.29-2.17 (m,1H), 2.13-1.91 (m,4H), 1.79-1.65 (m,4H),1.59 (m,1H), 1H, 0.71-1H, 9H), 1H, 9-1H, 9H, 1H, III, 1H, P₃) δ 8.44. carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 162.60-160.69 (m),137.21(d, J ═ 11.2Hz),136.02(d, J ═ 11.9Hz),134.81,133.43(d, J ═ 3.6Hz),133.20(d, J ═ 10.8Hz),132.75(d, J ═ 2.6Hz),131.97(d, J ═ 2.3Hz),131.37(d, J ═ 1.9Hz),129.97(d, J ═ 7.7Hz),129.68(d, J ═ 10.4Hz),129.54,129.36-128.40 (m),127.81,127.43,127.00,125.64,125.35,124.90,123.48,121.31,117.77-116.90 (m),93.78(d, J ═ 10.7Hz), 48(d, J ═ mass spectrum 3913.3 Hz),69.91,69.34(d, J ═ 13.2, 60, 17.53 (d, J ═ 8.7 Hz),23, 17.7, 17, 17.7 (d, J ═ 8.3.3 Hz),27.7, 7, 17.7, 7, 17,7, 23, 17,7, 8, Hz, 8, Hz, 8, Hz, 8, Hz, 8, 18, 8, Hz, 8, Hz, 18, 8, Hz, 18, Hz, 18, Hz, 18, Hz, 18, Hz, 18, Hz, 18, Hz, 18, Hz, 18, Hz, C, Hz, 18, Hz, C, Hz, C, Hz, C, Hz, C, Hz, C, Hz, C₃₅H₄₆NPIr⁺([M-BArF]⁺) 704.29916, experimental data 704.29920.

Example 34

(S_C,S_N) Synthesis of (E) -2g

In example 27 while simultaneously producing(S_C,S_N) -2 g' with a yield of 54%. Nuclear magnetic spectrum (400MHz, Chloroform-d) δ 8.09-8.02 (m,1H), 7.81-7.73 (m,2H),7.70(p, J ═ 2.1Hz,9H), 7.58-7.38 (m,12H), 7.25-7.11 (m,4H),7.06(s,2H),6.12(s,1H),4.32(d, J ═ 5.5Hz,1H),3.76(s,3H), 3.64-3.51 (m,2H), 3.15-3.06 (m,1H), 2.42-2.29 (m,1H), 2.23-2.06 (m,1H), 1.89-1.79 (m,1H), 1.78-1.62 (m,1H), 1.57-1.21H, 23-1.202 MHz, 1H), phosphorus (cl, 202 MHz), CDCl, 202H), nuclear magnetic spectrum₃) δ 16.35. carbon spectrum nuclear magnetic (126MHz, Chloroform-d) δ 162.38-161.00 (m),160.85,159.81,145.31,143.76(d, J ═ 14.3Hz),135.05(d, J ═ 2.2Hz),134.79,134.19(d, J ═ 12.0Hz),132.60(d, J ═ 2.3Hz),132.41(d, J ═ 2.6Hz),132.30(d, J ═ 10.5Hz),131.91(d, J ═ 2.4Hz),131.84,130.73(d, J ═ 10.0Hz), 129.94-129.60 (m), 129.35-128.40 (m),128.28,127.89,127.79,126.05,125.61(d, J ═ 3.2Hz),124.25,123.86,123.45,121.29,117.70-117.21 (m),97.80(d, J ═ 11.8Hz),92.47(d, J ═ 12.0Hz),83.37(d, J ═ 3.8, J ═ 3.85, J ═ 3.6, 19, 19.85, 19, 7.6, 3.6, 19(d, J ═ 3.6, h), theoretical 16.6, 3.6, h), theoretical d, J ═ 3.6, h, 3.6, h, theoretical d, h, 3.6, h, theoretical data (d, h), 3.6.6.6 Hz), 3.6Hz), theoretical data (d, h, 18, h, 3.6, 18h, 3.6h, 18h, 18h, etc., 3, etc., 18h, etc., 18h, etc., 3, etc., 18h, etc., 3, etc., 18h, etc., 3, 18h, etc., 18h, etc., 3, 18h, etc., 3, 18, etc., 3, 18h₄₃H₅₄NOPIr⁺([M-BArF]⁺) 824.35668, experimental data 824.35682.

EXAMPLE 35 asymmetric catalytic hydrogenation of five-membered Ring unsaturated carbonyl Compound

The Rong-Phos iridium complex obtained in example 21 was added

(S_C,R_N) -2a for the catalysis of the reaction, operating in particular as: weighing Rong-Phos iridium complex

(S_C,R_N) -2a (2.4mg) and Compound

(0.15mmol) was placed in a 10mL hydrogenation reaction tube equipped with a stirrer, vacuum-pumped, nitrogen-exchanged, toluene (1.5mL) was added under nitrogen atmosphere, and cooling with liquid nitrogen-vacuum-pumped, and this was repeated three times. Transferring the reaction tube into an autoclave, filling hydrogen (50atm) for reaction. After 12 hours the autoclave was opened and the product was analyzed by column chromatography for yield and by HPLC for enantiomeric excess (ee).

The specific catalytic reaction is shown as the following reaction formula:

column chromatography analysis revealed that: yield of target product 95%: HPLC analysis gave: ee ═ 66%

Of the target product¹H NMR(500MHz,Chloroform-d)δ7.36–7.27(m,5H),7.26–7.19(m,5H),4.48(q,J＝15.0Hz,2H),3.28(dd,J＝13.2,3.6Hz,1H),3.13(dt,J＝9.8,7.7Hz,1H),3.04(td,J＝9.2,3.5Hz,1H),2.86–2.71(m,2H),2.09–1.97(m,1H),1.77–1.67(m,1H)；¹³C NMR (126MHz, Chloroform-d) delta 175.80,139.38,136.51,129.12,128.66,128.45,128.10,127.52,126.32,46.79,44.78,43.66,37.03, 24.01. High resolution mass spectrometry theoretical data C₁₈H₁₉NNaO⁺288.1359, Experimental data 288.1359. Chirality was determined by HPLC using an ADH chiral column (hexane: 2-propanol ═ 90:10,1.0mL/min,210 nm); the retention time for the large enantiomer was 10.7min and for the small enantiomer 11.8 min. [ alpha ] to]_D ²²＝+55.48(c＝1.0,CHCl₃)。

Examples 36 to 47

Investigation of the Rong-Phos Iridium Complex according to the invention, Compound 2, ligand R²The effect of the substituents, hydrogen pressure and solvent on the reaction, the specific operation and the rest of the conditions are described in example 35. The reaction conditions and experimental results of the examples are shown in Table 1.

TABLE 1 reaction conditions and results of examples 36-47

(S) is illustrated by examples 36 to 47_C,R_N) -2b and (S)_C,S_N) -2 b' is the most suitable catalyst for the preparation of S and R configurations, notably Rong-Phos iridium complex (S)_C,R_N) -2b gave the S-configuration target in 96% yield, 90% ee, and Rong-Phos iridium complex (S)_C,S_N) The-2 b' gives the R-configuration target in 96% yield in 98% ee, a chiral inversion occurs, and the two iridium complexes (S)_C,R_N) -2b and (S)_C,S_N) The-2 b' is prepared from the same ligand Rong-Phos (S) -1b, the two differences are only in chirality on the two nitrogen atoms, and the control of the chirality of the nitrogen atoms realizes that the target products of two configurations can be obtained by using the same ligand with excellent enantioselectivity and excellent yield, which is very challenging.

Examples 48 to 71

Examining the general applicability of the substrates described in the present invention, the (S) pairs_C,R_N) -2b and (S)_C,S_N) 2 b' two iridium complexes were investigated, and the specific procedures and the remaining conditions were as described in example 43. The reaction conditions and experimental results of the examples are shown in Table 2.

The catalytic reaction is shown in the following formula (5):

TABLE 2 reaction conditions and results of examples 48-71

By way of examples 48 to 71, in the case of five-membered ring cyclic unsaturated carbonyl compoundsIn the application of symmetric catalytic hydrogenation reaction, the iridium complex (S)_C,R_N) 2b has better substrate universality, and the iridium complex (S)_C,S_N) The-2 b' shows excellent enantioselectivity on the basis of good universality, and has high reaction activity and enantioselectivity.

EXAMPLE 72 asymmetric catalytic hydrogenation of six-membered cyclic unsaturated carbonyl Compounds

The Rong-Phos iridium complex obtained in example 27 was added

(S_C,R_N) 2g of catalyst for the reaction, operating in particular: weighing Rong-Phos iridium complex

(S_C,R_N) -2g (2.5mg) and Compound

(0.15mmol) was placed in a 10mL hydrogenation reaction tube equipped with a stirrer, vacuum was applied, nitrogen was exchanged, methylene chloride (1.5mL) was added under nitrogen, and cooling with liquid nitrogen-vacuum application was repeated three times. The reaction tube was transferred to an autoclave and charged with hydrogen (20atm) for reaction. After 12 hours the autoclave was opened and the product was analyzed by column chromatography for yield and by HPLC for enantiomeric excess (ee).

The specific catalytic reaction is shown as the following reaction formula:

column chromatography analysis revealed that: yield of the target product 71%: HPLC analysis gave: ee is 75%

Of the target product¹H NMR(400MHz,Chloroform-d)δ7.32–7.12(m,5H),3.76–3.65(m,1H),3.62–3.51(m,1H),3.45–3.34(m,1H),2.69–2.57(m,2H),1.91–1.63(m,3H),1.54(s,9H)；¹³C NMR(101MHz,Chloroform-d)δ173.61,152.96,139.60,129.22,128.38,126.24,82.76,45.75,45.58,37.09,28.05,25.34,21.57. High resolution mass spectrometry theoretical data C₁₇H₂₃NNaO₃ ⁺312.1570, Experimental data 312.1571. Chirality was determined by HPLC using an OZ-3 chiral column (hexane: 2-propanol ═ 95:5,0.5mL/min,210 nm); the large enantiomer retention time was 17.3min and the small enantiomer retention time was 21.3 min. [ alpha ] to]_D ²²＝+82.33(c＝1.0,CHCl₃)。

Examples 73 to 77

The specific operation and the rest conditions were examined for the effect of the Rong-Phos iridium complex of the present invention, i.e., Compound 2, on the reaction under the hydrogen pressure and the solvent, and were described in example 72. The reaction conditions and experimental results of the examples are shown in Table 3.

TABLE 3 reaction conditions and results of examples 73-77

(S) is illustrated by examples 73 to 74_C,S_N) 2 g' is the most suitable catalyst, indicating a hydrogen pressure of 30atm as the most suitable pressure by examples 74 to 75 and DCE as the most suitable solvent by examples 75 to 77, giving the desired product of the R configuration in 99% yield with 96% ee.

Examples 78 to 87

Examination of the general applicability of the substrates described in the present invention, to (S)_C,S_N) 2 g' were examined, and the specific operations and the remaining conditions were as described in example 77. The reaction conditions and experimental results of the examples are shown in Table 4.

The catalytic reaction is shown in the following formula (6):

TABLE 4 reaction conditions and results of examples 78-87

By way of examples 78 to 87, the iridium complex (S) is used in the asymmetric catalytic hydrogenation of six-membered ring cyclic unsaturated carbonyl compounds_C,S_N) 2 g' has excellent substrate universality and very high reaction activity and enantioselectivity.

EXAMPLE 88 asymmetric catalytic hydrogenation of seven-membered cyclic unsaturated carbonyl Compounds

The Rong-Phos iridium complex obtained in example 27 was added

(S_C,R_N) -2g (2.5mg) and Compound

(0.15mmol) was placed in a 10mL hydrogenation reaction tube equipped with a stirrer, vacuum was applied, nitrogen was exchanged, methylene chloride (1.5mL) was added under nitrogen, and cooling with liquid nitrogen-vacuum application was repeated three times. The reaction tube was transferred to an autoclave and charged with hydrogen (30atm) for reaction. After 12 hours the autoclave was opened and the product was analyzed by column chromatography for yield and by HPLC for enantiomeric excess (ee).

The specific catalytic reaction is shown as the following reaction formula:

column chromatography analysis revealed that: yield of target product 98%: HPLC analysis gave: ee is 60%

Of the target product¹H NMR(400MHz,Chloroform-d)δ7.32–7.23(m,2H),7.22–7.16(m,3H),4.27–4.17(m,1H),3.35(dd,J＝15.3,10.6Hz,1H),3.26(dd,J＝14.1,5.3Hz,1H),2.96–2.85(m,1H),2.58(dd,J＝14.1,8.7Hz,1H),1.91–1.71(m,3H),1.52(s,9H),1.49–1.38(m,3H)；¹³C NMR (101MHz, Chloroform-d) delta 176.76,153.32,140.12,129.31,128.33,126.11,82.71,47.87,45.29,38.11,29.34,28.43, 28.05. High resolution mass spectrometry theoretical data C₁₈H₂₅NNaO₃ ⁺326.1726, Experimental data 326.1722. Chirality was determined by HPLC using an AS-H chiral column (hexane: 2-propanol ═ 98:2,1.0mL/min,210 nm); the retention time for the small enantiomer was 5.0min and for the large enantiomer 5.8 min. [ alpha ] to]_D ²²＝-9.27(c＝1.0,CHCl₃)。

Examples 89 to 90

The specific operation and the rest conditions were as described in example 88, considering the effect of the Rong-Phos iridium complex of the present invention, i.e., Compound 2, on the reaction. The reaction conditions and experimental results of the examples are shown in Table 5.

TABLE 5 reaction conditions and results of examples 89-90

(S) is illustrated by examples 96 to 97_C,S_N) 2 g' of the most suitable catalyst gave the desired product in the R configuration in 99% yield, 96% ee.

Examples 91 to 98

Examination of the general applicability of the substrates described in the present invention, to (S)_C,S_N) 2 g' were examined, and the specific operations and the remaining conditions were as described in example 90. The reaction conditions and experimental results of the examples are shown in Table 6.

The catalytic reaction is shown in the following formula (7):

TABLE 6 reaction conditions and results of examples 91-98

By way of examples 91 to 98, the iridium complex (S) is used in the asymmetric catalytic hydrogenation of a seven-membered ring, cyclic, unsaturated carbonyl compound_C,S_N) 2 g' has excellent substrate universality and very high reaction activity and enantioselectivity.

The protection of the present invention is not limited to the above embodiments. Variations and advantages that may occur to those skilled in the art may be incorporated into the invention without departing from the spirit and scope of the inventive concept, and the scope of the appended claims is intended to be protected.

Claims

1. A chiral bidentate nitrogen phosphine ligand Rong-Phos, which is characterized in that the chiral bidentate nitrogen phosphine ligand is a compound shown as the following formula (1) or an enantiomer or a racemate:

in the formula:

ar is selected from

R¹Is selected from

R²Is selected from C₁～C₁₂An alkyl group of,

R³Selected from hydrogen;

R⁴and R⁵Is C₁～C₁₂An alkyl group and hydrogen,

And hydrogen;

wherein R is^xAnd R^x’Are each independently selected from C₁～C₁₂Alkyl of (A), C₁～C₁₀Alkoxy group of (a);

n is an integer of 1 to 5.

2. The chiral bidentate phosphine nitride Rong-Phos is characterized in that the chiral bidentate phosphine nitride Rong-Phos is an optically pure compound with the structure shown as formula (S) -1 and (R) -1;

in the formula:

ar is selected from

R¹Is selected from

R²Selected from hydrogen, C₁～C₁₂An alkyl group of,

R³Selected from hydrogen;

R⁴and R⁵Is C₁～C₁₂An alkyl group and hydrogen,

And hydrogen;

n is an integer of 1 to 5.

3. The chiral bidentate phosphine nitride-Phos according to claim 1 or 2, characterized in that,

wherein the content of the first and second substances,

ar is selected from benzene ring;

R¹is selected from phenyl;

R²selected from the group consisting of tert-butyl, adamantyl, cyclohexyl, - (CH)₃)₂ ⁿBu、-(CH₂CH₃)₂Me、-(CH₂CH₃)₃4-methoxy-3, 5-di-tert-butylphenyl; r³Selected from hydrogen;

R⁴and R⁵Methyl and hydrogen, n-butyl and hydrogen, benzyl and hydrogen.

4. The chiral bidentate phosphine nitride-Phos according to claim 1, having the structure:

5. the preparation method of the chiral bidentate phosphine nitride ligand Rong-Phos as claimed in claim 2, which comprises the following steps:

the method comprises the following steps:

R⁶independently selected from tert-butyl;

The reaction scheme of the first step is as follows:

wherein the reaction formula of the second step is as follows:

wherein each group is as defined in claim 2.

6. The method according to claim 5,

the temperature of the first step reaction is-78-30 ℃;

the reaction time of the first step is 0.5 to 12 hours;

the temperature of the second step reaction is 0-30 ℃;

the time of the second step reaction is 0.5 to 12 hours.

7. The process for the preparation of chiral bidentate phosphine nitride ligand Rong-Phos according to claim 2, which comprises the following steps:

the second method comprises the following steps:

the first step is as follows: starting from a compound shown as the following formula (3), carrying out hydrolysis reaction under the action of hydrochloric acid to obtain intermediates shown as formula (A) and formula (B): wherein the compound of formula (3) comprises formula (S)_C,R_S) -3, formula (S)_C,S_S) -3, formula (R)_C,S_S) -3, formula (R)_C,R_S)-3；

Wherein the reaction formula of the first step is as follows:

the second step is that: the intermediates shown in the formula (A) and the formula (B) are subjected to condensation with aldehyde and reduction by a reducing agent to obtain chiral bidentate phosphine nitride Rong-Phos formula (S) -1 and formula (R) -1;

wherein the reaction formula of the second step is as follows:

wherein each group is as defined in claim 2;

R⁶independently selected from tertiary butyl.

8. The process for preparing a chiral bidentate phosphine nitride ligand Rong-Phos as claimed in claim 7,

the temperature of the first step reaction is 0-30 ℃;

the reaction time of the first step is 0.5 to 12 hours;

the temperature of the second step reaction is 0-30 ℃;

the time of the second step reaction is 0.5 to 12 hours.

9. The process for the preparation of chiral bidentate phosphine nitride ligand Rong-Phos according to claim 2, which comprises the following steps:

the third method comprises the following steps:

Wherein the reaction formula of the first step is as follows:

the second step is that: reacting an intermediate shown in a formula (A) and a formula (B) with R under the action of alkali⁴X and R⁵X is subjected to substitution reaction to obtain chiral bidentate nitrogen phosphine ligand Rong-Phos formula (S) -1 and formula (R) -1;

wherein the reaction formula of the second step is as follows:

wherein each group is as defined in claim 2;

R⁶independently selected from tertiary butyl.

10. The method according to claim 9,

the temperature of the first step reaction is 0-30 ℃;

the reaction time of the first step is 0.5 to 12 hours;

the temperature of the second step reaction is 0-100 ℃;

the time of the second step reaction is 1-24 hours.

11. Use of the chiral bidentate phosphine nitride ligand Rong-Phos according to claim 1 or 2 for the preparation of iridium complexes of Rong-Phos and for asymmetric catalytic hydrogenation.