3,4-diaminopyridine oxynitride chiral catalyst and application thereof in Steglich rearrangement

A technology of diaminopyridine nitrogen oxides and chiral catalysts, which is applied in the field of new chiral catalysts and asymmetric reactions, can solve the problems of poor enantioselectivity, low catalyst activity, and high cost. Strong regulation, high catalytic activity, and easy synthesis

Active Publication Date: 2019-03-01
HENAN NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] However, there are still various defects in the actual use of this prior art, mainly in the need to use expensive reagents and multi-step conversions in catalyst synthesis, poor enantioselectivity and low catalyst activity in catalytic applications.

Method used

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  • 3,4-diaminopyridine oxynitride chiral catalyst and application thereof in Steglich rearrangement
  • 3,4-diaminopyridine oxynitride chiral catalyst and application thereof in Steglich rearrangement
  • 3,4-diaminopyridine oxynitride chiral catalyst and application thereof in Steglich rearrangement

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Synthesis of Chiral 4-Nitro-3-(2-(2,6 Diisopropylbenzamido)pyrrolidinyl)pyridine 1-oxide

[0039]

[0040] In a 100mL flask was added L-2-(2,6 diisopropylbenzamido)pyrrolidine (5.48g, 20mmol), triethylamine (27.7mL, 200mmol, 10eq), 3-bromo-4-nitropyridine Nitrogen oxides (5.45g, 25mmol, 1.25eq) and tetrahydrofuran (35mL) were stirred overnight at 60°C to obtain a crude product which was separated by column chromatography to obtain 7.83g of a bright yellow solid with a yield of 95%, >99% ee. CHIRALCEL IA, n-hexane / 2-propanol=80 / 20, flow rate=1.0mL / min, λ=250nm, retention time: 10.843min.

[0041] 1 H NMR (400MHz, CDCl 3)δ8.21(s,1H),7.79–7.69(m,2H),7.62(s,1H),7.29(d,J=7.6Hz,1H),7.13(d,J=8.0Hz,2H), 4.51(t, J=7.6Hz, 1H), 3.84(td, J=10.4, 5.6Hz, 1H), 3.01(t, J=8.8Hz, 1H), 2.91–2.65(m, 3H), 2.28–2.14 (m,2H),2.08–1.94(m,1H),1.17(d,J=6.8Hz,6H),1.01(s,6H). 13 C NMR (100MHz, CDCl 3 )δ170.1, 146.1, 140.6, 133.6, 130.8, 130.0, 129.8, 128.9, 123.6, 122.7, 64.2, 54.0, 32.0, ...

Embodiment 2

[0046] Synthesis of Chiral 4-Chloro-3-(2-(2,6 Diisopropylbenzamido)pyrrolidinyl)pyridine 1-oxide

[0047]

[0048] Add chiral 4-nitro-3-(2-(2,6 diisopropylbenzamido)pyrrolidinyl)pyridine 1-oxide (2.06g, 5mmol), acetyl chloride (3.57 mL, 50mmol, 10eq), glacial acetic acid (10mL), the temperature was raised to 90-110°C for reaction, after the reaction was detected by TLC, the reaction solution was poured into ice water, and the weak alkalinity was adjusted with sodium hydroxide solution, and the obtained crude product was passed through Separated by column chromatography, 1.4 g of brown solid was obtained, with a yield of 70%, >99% ee. CHIRALCEL IA, n-hexane / 2-propanol=90 / 10, flow rate=1.0mL / min, λ=250nm, retention time: 12.632min(minor), 27.205min(major).

[0049] 1 H NMR (600MHz, CDCl 3 )δ8.09(d,J=2.4Hz,1H),7.84–7.69(m,2H),7.26(d,J=7.2Hz,1H),7.21–7.16(m,1H),7.12(d,J =7.8Hz,2H),4.64–4.58(m,1H),4.11–4.03(m,1H),3.30–3.23(m,1H),2.81(s,2H),2.61–2.52(m,1H), 2.29–2.21(m,1H),2...

Embodiment 3

[0054] Synthesis of Chiral 4-Pyrrolidinyl-3-(2-(2,6 Diisopropylbenzamido)pyrrolidinyl)pyridine 1-oxide

[0055]

[0056] Add chiral 4-chloro-3-(2-(2,6 diisopropylbenzamido)pyrrolidinyl)pyridine nitroxide (200mg, 0.5mmol) and pyrrolidine (1mL) to a 15mL sealed tube at 140 The reaction was carried out at ℃, and the reaction was completed. After vacuum distillation, the crude product was obtained and separated by column chromatography to obtain 133.0 mg of a light brown solid, with a yield of 61%, >99% ee. CHIRALCEL IA, n-hexane / 2-propanol=90 / 10, flow rate=0.5mL / min, λ=250nm, retention time: 20.270min(minor), 35.368min(major).

[0057] 1 H NMR (400MHz, CDCl 3 )δ8.36(s,1H),8.32(s,1H),7.77(dd,J=7.2,2.0Hz,1H),7.22(t,J=7.6Hz,1H),7.08(d,J=7.6 Hz,2H),6.57(d,J=7.2Hz,1H),4.30(t,J=7.2Hz,1H),3.67–3.57(m,1H),3.45–3.34(m,2H),3.25–3.14 (m,2H),2.84–2.71(m,3H),2.50–2.41(m,1H),2.28–2.18(m,1H),2.14–2.04(m,1H),2.03–1.93(m,3H) ,1.91–1.82(m,2H),1.01(d,J=6.8Hz,12H). 13 C NMR (150MHz, CDCl 3...

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Abstract

The invention discloses a 3,4-diaminopyridinium oxynitride chiral catalyst and application thereof in Steglich rearrangement, and belongs to the technical field of asymmetric synthesis in organic chemistry. The 3,4-diaminopyridine oxynitride chiral catalyst is obtained by using 3-bromo 4-nitropyridine nitroxene oxynitride and D or L-prolinamide as raw materials and conducting chlorination and amination. The catalyst is used for asymmetric Steglich rearrangement of O-acyl dihydropyrazolone to obtain the alpha-quaternary carbon chiral C-acyl dihydropyrazolone, and high yield and excellent enantioselectivity are achieved. The catalyst is novel in structure, simple in synthesis method and excellent in catalytic rearrangement effect.

Description

technical field [0001] The present invention relates to a novel chiral catalyst and its application in asymmetric reactions, in particular to 3,4-diaminopyridine nitroxide chiral catalysts and its application in Steglich rearrangement, which belongs to the asymmetrical reaction in organic chemistry The field of synthetic technology. Background technique [0002] Acyl transfer is one of the most commonly used transformations in nature and organic synthesis. The development of chiral non-enzymatic acyl transfer catalysts has become a vibrant field of research over the past two decades, and structurally diverse catalysts have been reported ((a) Ruble, J.C.; Fu, G.C.J.Am.Chem.Soc. 1998, 120, 11532. (b) Shaw, S.A.; Aleman, P.; Vedejs, E.J. Am. Chem. Soc. 2003, 125, 13368. (c) Joannesse, C.; Johnston, C.P.; Smith, A.D. Angew. Chem., Int. Ed. 2009, 48, 8914. (d) Zhang, Z.; Xie, F.; Jia, J.; , D.; Ooi, T.Angew.Chem., Int.Ed.2010,49,5567.(f) Cruchter, T.; Meggers, E.ACS Catal.2017...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/04B01J31/02C07B53/00C07D263/42C07C231/10C07C237/22
CPCB01J31/0244C07B53/00C07B2200/07C07C231/10C07D263/42C07D401/04C07C237/22
Inventor 谢明胜单梦张业飞武晓霞渠桂荣郭海明
Owner HENAN NORMAL UNIV
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