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Chiral spiro phosphine-nitrogen-sulfur tridentate ligand and preparation method and application thereof

一种螺环、手性的技术，应用在羧酸酰胺旋光异构体制备、羧酸酯制备、羧酸酰胺制备等方向，达到活性高、反应条件温和、效率高的效果

Active Publication Date: 2015-09-09
ZHEJIANG RAYBOW PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the catalysts for highly efficient asymmetric catalytic hydrogenation of β-alkyl-β-ketoesters are limited to ruthenium halide catalysts with chiral bisphosphine ligands, and the TON of most catalysts does not exceed 10,000, and it is often necessary to add parametallic Reactor has corrosive hydrochloric acid and other additives (Ohkuma, T.; Noyori, R. in Handbook of Homogeneous Hydrogenation, Eds.: de Vries, J.G.; Elsevier, C.J., Wiley-VCH, Weinheim, 2007, pp.1105)

Method used

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  • Chiral spiro phosphine-nitrogen-sulfur tridentate ligand and preparation method and application thereof
  • Chiral spiro phosphine-nitrogen-sulfur tridentate ligand and preparation method and application thereof
  • Chiral spiro phosphine-nitrogen-sulfur tridentate ligand and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] (R)-N-(2-(phenylthio)ethyl)-7-bis-(3,5-di-tert-butylphenyl)phosphino-7'-amino-1,1'-spirodihydro Synthesis of Indene(Ia)

[0033]

[0034] In a nitrogen atmosphere, weigh (R)-7'-bis-(3,5-di-tert-butylphenyl)phosphino-7'-amino-1,1'-spirodihydroindene (193mg, 0.3mmol ), pyridine (119 mg, 1.5 mmol) and 2 mL of dichloromethane in a 15 mL dry Schlenk tube. After stirring at room temperature to dissolve the solid, a dichloromethane solution (2 mL) of thiophenylacetyl chloride (84 mg, 0.45 mmol) was added dropwise to the system under cooling in an ice-water bath. After the drop was completed, after stirring at room temperature for 2 hours, TLC detected that the reaction was complete (petroleum ether: ethyl acetate = 10:1). The organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, and allowed to stand. The desiccant was removed by suction filtration, and the filtrate was desolvated by a rotary evaporator, and the crude product obtained was ...

Embodiment 2

[0039] (R)-N-(2-(phenylthio)ethyl)-7'-bis-(3,5-dimethylphenyl)phosphino-7'-amino-1,1'-spirodihydro Synthesis of Indene(Ib)

[0040]

[0041] Refer to Example 1 for specific operation, white solid, yield: 65%.

[0042] Mp 58-60°C, 277.0 (c 0.5, CHCl 3 ). 1 H NMR (400MHz, CDCl 3 )δ7.28-7.08(m, 8H), 7.03(t, J=7.6Hz, 1H), 6.84(s, 1H), 6.81(s, 1H), 6.72-6.63(m, 3H), 6.58(d , J=7.1Hz, 2H), 5.92(d, J=7.9Hz, 1H), 3.17-3.11(m, 1H), 3.08-2.96(m, 4H), 2.78(td, J=12.9, 6.5Hz, 1H), 2.68-2.53(m, 2H), 2.53-2.43(m, 1H), 2.43-2.33(m, 2H), 2.33-2.23(m, 1H), 2.17(s, 6H), 2.16(s, 6H); 31 P NMR (162MHz, CDCl 3 )δ-22.6(s); 13 C NMR (101MHz, CDCl 3)δ153.1 (d, J=25.3Hz), 144.6 (d, J=2.8Hz), 144.1 (d, J=7.7Hz), 143.5 (d, J=1.8Hz), 139.5 (d, J=13.0 Hz), 137.3(d, J=6.0Hz), 137.1(d, J=8.1Hz), 136.2(d, J=13.3Hz), 135.8, 135.0, 134.8, 134.4(d, J=2.9Hz), 133.4 (d, J=3.4Hz), 132.5, 132.2, 130.9, 130.7, 130.4, 130.1, 129.5, 129.0, 128.1, 127.5, 126.4, 126.0, 113.7, 107.9, 61.7 (d, J=3.2Hz), 41...

Embodiment 3

[0044] Synthesis of (R)-N-(2-(phenylthio)ethyl)-7'-diphenylphosphino-7'-amino-1,1'-spiroindene (Ic)

[0045]

[0046] See Example 1 for specific operation, white solid, yield: 51%.

[0047] Mp 55-58°C, 245.5 (c 0.5, CHCl 3 ). 1 H NMR (400MHz, CDCl 3 )δ7.31-6.91(m, 19H), 6.65(d, J=7.3Hz, 1H), 5.93(d, J=7.9Hz, 1H), 3.27-3.18(m, 1H), 3.11-2.93(m , 4H), 2.93-2.81(m, 1H), 2.68(t, J=6.5Hz, 2H), 2.53-2.33(m, 3H), 2.32-2.23(m, 1H), 2.18-2.08(m, 1H ); 31 P NMR (162MHz, CDCl 3 )δ-22.3(s); 13 C NMR (101MHz, CDCl 3 )δ153.3 (d, J=25.3Hz), 144.6 (d, J=3.1Hz), 144.3 (d, J=7.8Hz), 143.4, 139.7 (d, J=13.9Hz), 136.8 (d, J =14.0Hz), 135.6, 134.5(d, J=2.5Hz), 134.34, 134.25, 134.1, 134.0, 133.3, 133.2(d, J=3.5Hz), 133.1, 130.0, 129.0, 128.4(d, J=3.6 Hz), 128.1(d, J=5.5Hz), 128.0(d, J=7.3Hz), 127.7(d, J=9.9Hz), 126.4, 126.3, 113.8, 108.0, 61.7(d, J=3.2Hz) , 41.3, 40.0 (d, J=5.3Hz), 36.2, 33.9, 31.5, 31.1. HRMS (MALDI) Calcd for C 37 h 35 NPS[M+H] + : 556.2222; Found: 556.2216.

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Abstract

The invention relates to a chiral spiro phosphine-nitrogen-sulfur tridentate ligand and a preparation method and application thereof. The chiral spiro phosphine-nitrogen-sulfur tridentate ligand is a compound with a formula I or formula II, or a racemate or optical isomer thereof, or a catalytically-acceptable salt thereof, and has the main structure characteristic of having a chiral spiro indan skeleton and a sulfoether group. The chiral spiro phosphine-nitrogen-sulfur tridentate ligand can be synthesized from chiral starting materials of 7-diaryl / alkyl phosphino-7'-amino-1,1'-spiro indan compound with a spiro skeleton. The chiral spiro phosphine-nitrogen-sulfur tridentate ligand and transition metal salt form a complex, which can be used in catalysis of an asymmetric catalytic hydrogenation reaction of a carbonyl compound. Especially, the iridium complex shows high catalytic activity (catalyst amount of 0.0002% mol) and enantioselectivity (up to 99.9%ee) in asymmetric hydrogenation reaction of beta-alkyl-beta-keto ester, and has practical value.

Description

technical field [0001] The present invention relates to a class of chiral spirocyclic phosphine-nitrogen-sulfur tridentate ligands and their preparation methods and applications, in particular to a preparation method for a class of chiral spirocyclic phosphine-nitrogen-sulfur tridentate ligands with a spirocyclic skeleton The invention relates to the application in the asymmetric catalytic hydrogenation reaction of carbonyl compounds and belongs to the technical field of organic synthesis. Background technique [0002] Asymmetric reactions catalyzed by chiral transition metal complexes are the most effective way to obtain optically active chiral compounds, and have been widely used in the industrial production of chiral drugs. In asymmetric catalytic reactions, chiral ligands and their catalysts are the key to achieve efficient and high enantioselective synthesis of chiral compounds. For this reason, the development of novel efficient and highly selective chiral ligands and...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F9/50B01J31/24C07B41/02C07C67/31C07C69/675C07C69/708C07C269/06C07C271/22C07C231/12C07C235/06C07C29/145C07C33/22
CPCC07C29/145C07C67/31C07C269/06C07C69/675C07C69/708C07F15/0033C07C231/18C07B53/00B01J2531/0241B01J31/189B01J31/226B01J31/249B01J2231/643B01J2531/827C07F9/5022C07F9/655363C07C271/22C07C235/06C07C231/12B01J37/04C07C29/149C07F9/5054
Inventor 周其林谢建华包登辉王立新
Owner ZHEJIANG RAYBOW PHARM CO LTD
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