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Preparation methods and applications of chiral spirophosphine-nitrogen-phosphine tridentate ligand and iridium catalyst thereof

A catalyst and spiro ring technology, which is applied in the field of organic synthesis, can solve the problems such as the difficulty in recognizing the chirality of the carbonyl plane of the substrate by the catalyst, and achieve the effects of excellent enantioselectivity, mild reaction conditions and great practical value.

Active Publication Date: 2020-08-04
ZHEJIANG JIUZHOU PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The difficulty of high enantioselective asymmetric catalytic hydrogenation of simple dialkyl ketones, such as methyl ethyl ketone, is that the chiral recognition of the catalyst to the carbonyl plane of the substrate is very difficult

Method used

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  • Preparation methods and applications of chiral spirophosphine-nitrogen-phosphine tridentate ligand and iridium catalyst thereof
  • Preparation methods and applications of chiral spirophosphine-nitrogen-phosphine tridentate ligand and iridium catalyst thereof
  • Preparation methods and applications of chiral spirophosphine-nitrogen-phosphine tridentate ligand and iridium catalyst thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] The synthetic route of ligand Ia:

[0039]

[0040] In an argon atmosphere, weigh (R)-7′-bis-(3,5-di-tert-butylphenyl)phosphino-7′-amino-1,1′-spirodihydroindane 4a (300 mg, 0.46mmol) into a 100mL dry Schlenk tube, inject 12mL of anhydrous methanol into the syringe, and stir to dissolve. 2-Diphenylphosphinebenzaldehyde (176 mg, 0.61 mmol) and glacial acetic acid (42 μL) were added. The reaction was stirred at room temperature for 3 hours. Open the anti-port plug and pour NaBH at one time 3 CN (87mg, 1.38mmol), the reaction was carried out at 40°C for 15 hours. Cool to room temperature after the reaction, spin the system to dryness, add dichloromethane to dissolve, and quench with saturated sodium bicarbonate solution. Extract with dichloromethane, combine the organic phases, dry the organic phases with anhydrous magnesium sulfate, remove the desiccant by suction filtration, and remove the solvent from the filtrate with a rotary evaporator. The residue was subject...

Embodiment 2

[0052] The synthetic route of ligand Ib:

[0053]

[0054] Synthesis of intermediate 3a:

[0055] Weigh Pd(OAc) in a 25mL Schlenk tube 2 (56mg), dppp (103mg), 2a (310mg), replaced with argon, injected into degassed DMSO (4.0mL), stirred evenly, injected with o-bromobenzaldehyde (118μL) and diisopropylethylamine (248 μL), heated in an oil bath to 100°C for 20 hours. After the reaction, cool to room temperature, add 10 mL of ethyl acetate and 10 mL of water, extract with ethyl acetate, combine the organic phases, dry the organic phases with anhydrous magnesium sulfate, remove the desiccant by suction filtration, and remove the solvent from the filtrate with a rotary evaporator. The residue was subjected to silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain 242 mg of white solid 3a with a yield of 66%.

[0056] Data for Intermediate 3a:

[0057] White solid, melting point 202-204°C.

[0058] 1 H NMR (400MHz, CDCl 3 )

[0059] δ10.74(s,...

Embodiment 3

[0091] The synthetic route of ligand Ic:

[0092]

[0093] Synthesis of Intermediate 3b:

[0094] Weigh Pd(OAc) in a 25mL Schlenk tube 2 (112mg), dppp (206mg), 2b (1026mg), replaced with argon, injected into degassed DMSO (8.0mL), stirred evenly, injected with o-bromobenzaldehyde (234μL) and diisopropylethylamine (496 μL), heated in an oil bath to 100°C for 20 hours. After the reaction, cool to room temperature, add 20 mL ethyl acetate and 20 mL water, extract with ethyl acetate, combine the organic phases, dry the organic phases with anhydrous magnesium sulfate, remove the desiccant by suction filtration, and remove the solvent from the filtrate with a rotary evaporator. The residue was subjected to silica gel column chromatography (petroleum ether: ethyl acetate = 5:1) to obtain 752 mg of white solid 3b with a yield of 71%.

[0095] Data for intermediate 3b:

[0096] White solid, melting point 58-60°C.

[0097] 1 H NMR (400MHz, CDCl 3 )

[0098] δ10.79(s, 1H), 8....

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Abstract

The invention relates to preparation methods and applications of a chiral spirophosphine-nitrogen-phosphine tridentate ligand SpiroPNP and an iridium catalyst Ir-SpiroPNP thereof. The chiral spirophosphine-nitrogen-phosphine tridentate ligand is a compound represented by a formula I, or a racemate or an optical isomer thereof, or a catalytically acceptable salt thereof, and is mainly structurallycharacterized by having a chiral spiro indane skeleton and a phosphine ligand with a large steric hindrance substituent. The chiral spirophosphine-nitrogen-phosphine tridentate ligand can be synthesized by taking a 7-diaryl / alkylphosphino-7'-amino-1,1'-spiro indane compound with a spiro skeleton as a chiral starting raw material. The iridium catalyst of the chiral spirophosphine-nitrogen-phosphinetridentate ligand is a compound represented by a formula II which is described in the specification, or a raceme or an optical isomer, or a catalytically acceptable salt thereof, can be used for catalyzing asymmetric catalytic hydrogenation reaction of carbonyl compounds, particularly shows high yield (greater than 99%) and enantioselectivity (as high as 99.8% ee) in asymmetric hydrogenation reaction of simple dialkyl ketone, and has practical value.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and relates to a preparation method and application of a class of chiral spirocyclic phosphine-nitrogen-phosphine tridentate ligands and iridium catalysts thereof, in particular to a class of chiral phosphine-nitrogen-phosphine with a spiro ring skeleton Preparation method of tridentate ligand and its iridium catalyst and application in asymmetric catalytic hydrogenation of simple dialkyl ketones. Background technique [0002] Transition metal asymmetric catalytic hydrogenation has the advantages of high atom economy, mild reaction conditions, high catalytic activity, and good enantioselectivity. It has become one of the most simple, convenient and efficient methods to obtain chiral molecules, and has It has been widely used in the industrial production of drug molecules and chiral pesticides, such as L-dopa, carbapenicillin, Jin Duoer, etc. It is precisely because of their outstanding...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F15/00B01J31/24
CPCC07F15/004B01J31/2409B01J2531/827B01J2231/341C07F9/5022C07C29/145C07B2200/07C07C67/31C07C2601/14C07C2601/18C07C2601/10C07C2601/04C07C41/26C07C37/002C07B53/00B01J2531/0241B01J2231/643B01J31/249B01J31/189B01J31/0212C07C31/12C07C31/125C07C31/20C07C33/025C07C69/675C07C31/1355C07C31/133C07C33/12C07C31/1336C07C33/20C07C43/23C07C39/11C07C35/08C07C33/26B01J31/1805B01J37/00
Inventor 周其林张丰华谢建华王立新
Owner ZHEJIANG JIUZHOU PHARM CO LTD
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