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CN-118026834-B - Preparation method of planar chiral indene metal complex with phenylindene skeleton, synthesis intermediate and catalytic application

CN118026834BCN 118026834 BCN118026834 BCN 118026834BCN-118026834-B

Abstract

The application belongs to the technical field of asymmetric catalytic synthesis, and particularly relates to a preparation method, a synthesis intermediate and catalytic application of a planar chiral indene metal complex with a benzoindene skeleton. The application provides a key intermediate- (R) -configuration, (S) -configuration chiral indenone for preparing the planar chiral indene metal complex and a chiral indene ligand without a coordinated side arm prepared based on the chiral indene ketone, wherein the chiral indene ligand has strong modifiable property and is easy to complex with a transition metal compound to prepare a single planar chiral indene metal complex, the planar chiral indene metal complex can be used as a catalyst for various asymmetric hydrocarbon activation reactions, and the chiral indene metal complex does not need to separate stereoisomers in the synthesis process, so that the synthesis difficulty and the cost in all aspects are greatly reduced.

Inventors

  • WANG JUN
  • Guo Weicong

Assignees

  • 中山大学

Dates

Publication Date
20260512
Application Date
20240208

Claims (9)

  1. 1. A chiral indanone of (R) -configuration having a chemical structure as shown in formula (1), and a chiral indanone of (S) -configuration having a chemical structure as shown in formula (2): (1), Formula (2).
  2. 2. A method of synthesizing a chiral indanone, the method comprising: Step 1, performing condensation-reduction reaction on (R) -configuration, (S) -configuration or chiral ring aldol formed by (R) -configuration and (S) -configuration in any proportion and isopropyl malonate to generate (R) -configuration, (S) -configuration or ring aldonic acid formed by (R) -configuration and (S) -configuration in any proportion; The chiral cyclic aldehyde of the (R) -configuration has a chemical structure shown in a formula (3), the chiral cyclic aldehyde of the (S) -configuration has a chemical structure shown in a formula (4), the cyclic propionic acid of the (R) -configuration has a chemical structure shown in a formula (5), and the cyclic propionic acid of the (S) -configuration has a chemical structure shown in a formula (6): (3), Formula (4); (5), Formula (6); Step 2, the (S) -configuration, (R) -configuration or the cyclopropionic acid formed by the (S) -configuration and the (R) -configuration in any proportion is reacted in the methylsulfonic acid to respectively generate the chiral indenone formed by the (R) -configuration and the (S) -configuration in any proportion; the chiral indenone in the (R) -configuration has a chemical structure shown in a formula (1), and the chiral indenone in the (S) -configuration has a chemical structure shown in a formula (2): (1), Formula (2).
  3. 3. A chiral indene ligand of (R) -configuration having a chemical structure as shown in formula (7), a (S) -configuration having a chemical structure as shown in formula (8), or a chiral indene ligand of (R) -configuration and (S) -configuration in any ratio. (7), Formula (8); Wherein in the formula (7) and the formula (8), R 1 is selected from alkyl, heteroalkyl, heteroaryl or aryl, and R 2 is selected from H, alkyl, heteroalkyl, heteroaryl or aryl.
  4. 4. A process for synthesizing the chiral indene ligand of claim 3, comprising reacting the chiral indene ketone of claim 1 with a nucleophile selected from the group consisting of grignard reagent RMgX, organolithium reagent RLi, organocopper reagent R 2 CuLi, organozinc reagent R 2 Zn, and organoaluminum R 3 Al reagent, followed by dehydration.
  5. 5. A (R) -configuration, a (S) -configuration, or a planar chiral indene metal complex having a benzindene skeleton constituted by any ratio of the (R) -configuration to the (S) -configuration, the (R) -configuration planar chiral indene metal complex having a chemical structure as shown in formula (9), the (S) -configuration planar chiral indene metal complex having a chemical structure as shown in formula (10): (9), Formula (10); Wherein in the formula (9) and the formula (10), R 1 is selected from alkyl, heteroalkyl, heteroaryl or aryl, R 2 is selected from H, alkyl, heteroalkyl, heteroaryl or aryl, M is selected from rhodium, iridium, iron, cobalt, ruthenium, scandium, yttrium or lanthanum, L is selected from mono-olefin, diene, aromatic hydrocarbon, halogen anion, acid radical anion, cyclopentadiene anion, indene anion, o-aminobenzyl anion, carbon monoxide, phosphine ligand, aza-aromatic hydrocarbon, amine compound or sulfur compound, n is the number of ligand, and n is an integer of 0-5.
  6. 6. A method of synthesizing the planar chiral indene metal complex of claim 5, comprising reacting the chiral indene ligand of claim 3 with a transition metal compound to form a planar chiral indene metal complex, L of which is selected from mono-or di-olefin ligands, aromatic hydrocarbons, halide anions, acid anions, cyclopentadiene anions, indene anions, anthranilate anions, carbon monoxide, phosphine ligands, aza-aromatic hydrocarbons, amine compounds, or sulfur compounds, n represents the number of ligands, and n is an integer from 0 to 5.
  7. 7. A method of synthesizing the planar chiral indene metal complex of claim 5, the method comprising: step a, reacting the chiral indene ligand of claim 3 with a transition metal compound to form a first planar chiral indene metal complex, wherein L of the first planar chiral indene metal complex is selected from a mono-olefin or a di-olefin ligand; And b, reacting the first planar chiral indene metal complex in the step a with an oxidant, wherein the oxidant is halogen simple substance, hydrogen halide, peroxide or metal oxidant, so as to generate a second planar chiral indene metal complex, L of the second planar chiral indene metal complex is halogen anion and acid radical anion, n represents the number of ligands, and n is an integer of 0-5.
  8. 8. The method according to claim 6 or 7, wherein the transition metal compound is selected from rhodium compounds, iridium compounds, iron compounds, cobalt compounds, ruthenium compounds, scandium compounds, yttrium compounds or lanthanum compounds.
  9. 9. Use of a planar chiral indene metal complex of claim 5 or prepared by a method of any of claims 6 to 8 as a catalyst in catalyzing asymmetric hydrocarbon activation reactions.

Description

Preparation method of planar chiral indene metal complex with phenylindene skeleton, synthesis intermediate and catalytic application Technical Field The application belongs to the technical field of asymmetric catalytic synthesis, and particularly relates to a preparation method, a synthesis intermediate and catalytic application of a planar chiral indene metal complex with a benzoindene skeleton. Background Asymmetric catalysis is an important method for synthesizing chiral organic molecules. The chiral indene metal catalyst is used as a catalyst with high reactivity and functional group compatibility, and is widely applied to asymmetric catalytic synthesis. The chiral indene ligand without the coordination side arm has great application value in asymmetric catalysis, wherein the chiral indene ligand without the coordination side arm refers to an indene ring without a coordination chiral substituent group, and a chiral framework on the indene ring can provide chiral control. The chiral indene ligand mainly based on chiral menthol skeleton reported in various documents can be complexed with zirconium, yttrium, cobalt and rhodium to form a metal catalyst. The catalyst has better catalytic effects in the asymmetric alkyl aluminizing reaction, the asymmetric hydroamination reaction of olefin, the asymmetric hydrogenation reaction and the like. In 2023, loginov problem group succeeded in synthesizing chiral indene ligand without coordination side arm by using natural product alpha-pinene as raw material, which is stereospecific when coordinated with rhodium, and chiral separation is not needed, but the structure is difficult to reform. The catalyst is applied to asymmetric hydrocarbon activation synthesis of chiral hydrogenated isoquinolinone. In recent years, progress has also been made in preparing planar chiral indene metal catalysts from achiral, non-coordinating side-arm indene ligands. The task group of Baik and Blakey in 2020 successfully resolved racemic rhodium complexes containing prochiral indene ligands by chiral preparative liquid chromatography to obtain optically pure chiral indene rhodium catalysts. The catalyst is successfully applied to asymmetric amidation reaction of allyl compounds and asymmetric aza cyclization of non-activated olefins. Most indene ligands are not specific enough in stereoselectivity when being complexed with metal, stereoisomers can be generated, separation and purification are needed through chiral preparation liquid chromatography or recrystallization, operation is difficult, experimental cost is high, and synthesis of optical pure indene metal complex is difficult. Secondly, the existing chiral indene ligand without a coordinated side arm has poor modifiable property, and is difficult to obtain wide application in asymmetric catalysis and obtain excellent catalysis results. In addition, the existing chiral indene ligand without a coordination side arm has few types and the chiral indene ligand without the coordination side arm is very deficient. Disclosure of Invention Based on the above, the application develops a chiral indene ligand which has an easily-improved structure and can stereospecifically complex metal and has no coordination side arm, and a key intermediate (chiral indenone) for preparing the chiral indene ligand. Furthermore, the planar chiral indene metal complex prepared based on the chiral indene ligand has the performance of catalyzing asymmetric hydrocarbon activation reaction, and has excellent yield and enantioselectivity. The first aspect of the present application provides a chiral indanone of (R) -configuration having a chemical structure as shown in formula (1), and of (S) -configuration having a chemical structure as shown in formula (2): In a second aspect, the application discloses a method for synthesizing chiral indanone, the method comprising: Step 1, performing condensation-reduction reaction on (R) -configuration, (S) -configuration or chiral ring aldol formed by (R) -configuration and (S) -configuration in any proportion and isopropyl malonate to generate (R) -configuration, (S) -configuration or ring aldonic acid formed by (R) -configuration and (S) -configuration in any proportion; The chiral cyclic aldehyde of the (R) -configuration has a chemical structure shown in a formula (3), the chiral cyclic aldehyde of the (S) -configuration has a chemical structure shown in a formula (4), the cyclic propionic acid of the (R) -configuration has a chemical structure shown in a formula (5), and the cyclic propionic acid of the (S) -configuration has a chemical structure shown in a formula (6): Step 2, the (S) -configuration, (R) -configuration or the cyclopropionic acid formed by the (S) -configuration and the (R) -configuration in any proportion is reacted in the methylsulfonic acid to respectively generate the chiral indenone formed by the (R) -configuration and the (S) -configuration in any proportion; the chiral indenone in the (R) -confi