EBINOL axial chiral compound as well as synthesis method and application thereof

A compound and axial chiral technology, which is applied in the field of EBINOL axial chiral compounds and their synthesis, can solve problems such as poor enantioselectivity

Active Publication Date: 2019-07-23
SOUTH UNIVERSITY OF SCIENCE AND TECHNOLOGY OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But for some types of reactions, the enantioselectivity effect is not good, therefore, ligands with TADDOL and SPINOL chiral skeletons were developed

Method used

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  • EBINOL axial chiral compound as well as synthesis method and application thereof
  • EBINOL axial chiral compound as well as synthesis method and application thereof
  • EBINOL axial chiral compound as well as synthesis method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0076] Synthesis of substrates

[0077]

[0078] At 0°C, under stirring conditions, to concentrated H 2 SO 4 (0.98mL, 18.0mmol) in MeOH (20mL), 2-naphthol compound J (12.0mmol) were added KI (2.19g, 13.2mmol) and 30% H 2 o 2 (2.72mL, 24.0mmol), the mixture was stirred at 0°C for about 2 hours, after the completion of the reaction was monitored by TLC, the mixture was diluted with water, extracted twice with 50mL DCM, and the combined organic phase was successively washed with 20mL saturated Na 2 S 2 o 3 , 40mL H 2 O and 50mL of brine, washed with Na 2 SO 4 After drying and concentration under reduced pressure, the residue was purified by recrystallization to give the product K.

[0079] Under argon protection, compound K (10.0 mmol), Pd(PPh 3 ) 4 (1.16g, 1.00mmol), CuI (381mg, 2.00mmol) and 40mL of anhydrous THF, then added 3,3-dimethyl-1-butyne (2.46mL, 20.0mmol) and i PR 2 NH (4.20 mL, 30.0 mmol). The Schlenk tube was sealed, and the mixture was stirred at ro...

Embodiment 2

[0105] Screening of reaction conditions: 6a (0.10mmol), 1a (0.15mmol) and catalyst (5mol%) were reacted in 2.0mL solvent for 36 hours.

[0106]

[0107]

[0108]

[0109] b: separation yield; c: determined by HPLC analysis; d: 48 hours of reaction; e: 0.2 mmol of 6a, 0.3 mmol of 1a.

[0110] 1-(3,3-Dimethyl-1-ynyl)-2-naphthol 6a and 2-naphthol 1a were selected as substrates. In the presence of SPINOL phosphoric acid (S)-C1, the reaction proceeded smoothly to 86 % yield, 71% ee afforded axial chiral EBINOL(aR)-7a. Then, phosphoric acid catalysts with different chiral skeletons and substituents were screened, and it was found that both SPINOL phosphoric acid and BINOL phosphoric acid C10 had excellent enantioselectivity, and C3 was the catalyst with the best effect. After screening the solvent, it was found that DCM was the best choice, and after screening the temperature, it was found that the reaction at 10° C. for 48 hours had the best effect (98% ee, 93% yield).

...

Embodiment 3

[0117]

[0118] Following the general synthetic procedure, 7a was obtained as a white solid in 96% yield, 98% ee.

[0119] 1 H NMR (400MHz, acetone-d 6 )δ8.99(brs,2H),8.73(d,J=8.7Hz,1H),8.10(s,1H),7.80(d,J=8.0Hz,1H),7.76(d,J=8.9Hz, 1H), 7.74–7.72(m, 1H), 7.68(d, J=8.8Hz, 1H), 7.59(s, 1H), 7.34(t, J=7.3Hz, 1H), 7.27(d, J=8.8 Hz, 1H), 7.21–7.18(m, 2H), 7.05(d, J=8.8Hz, 1H), 6.17(s, 1H), 1.04(s, 9H). 13 C NMR (101MHz, acetone-d 6 )δ153.27,152.90,152.23,135.58,134.49,130.50,130.24,130.13,129.89,129.62,129.11,127.10,126.88,126.30,125.56,124.62,124.34,123.86,123.49,121.14,119.16,118.44,36.13,29.96。 HRMS (ESI) accurate mass calculation [M-H] - C 26 h 23 o 2 - , m / z: 367.1704, measured value: 367.1699. IR(KBr,cm -1 ) 3464, 3364, 2961, 1622, 1516, 1341, 1269, 1200, 816, 750. M.P. 226-228°C. (c=0.4, CHCl 3 ). HPLC conditions: HPLC DAICEL CHIRALPAK ID, n-hexane / isopropanol=95 / 5, 0.5mL / min, λ=230nm, t R (minor) = 10.0min,t R (major) = 11.6 min, ee = 98%.

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Abstract

The invention belongs to the field of axial chiral compounds, and discloses an EBINOL axial chiral compound. The EBINOL axial chiral compound has the following general formula(the formula is shown inthe description), wherein R<1> and R<2> are respectively and independently selected from hydrogen, alkyl, alkynyl, alkenyl, phenyl, alkoxyl, amine, halogen, trifluoromethyl, cyano group, hydroxyl, aldehyde group, carboxy group, acetyl, ester group, nitro group, amide group, sulfonyl group, sulfonic group, sulfydryl and sulfanyl. The invention further discloses a synthesis method and application ofthe EBINOL axial chiral compound. According to the EBINOL axial chiral compound as well as the synthesis method and application thereof, the axial chiral EBINOL compound with a novel structure is designed, and the skeleton of the EBINOL is constructed by the asymmetric hydrogenation and arylation of chiral acid catalyzed aryl alkyne; the synthesis method has good yield, and excellent E / Z selectivity and enantioselectivity; catalysts, such as chiral phosphoric acid and chiral phosphoramidite, used for asymmetric reactions can be derived from the EBINOL compound.

Description

technical field [0001] The invention belongs to the field of axial chiral compounds, and in particular relates to an EBINOL axial chiral compound and its synthesis method and application. Background technique [0002] Since 1980, BINOL with an axial chiral 1,1′-binaphthyl framework has been widely used as a ligand for asymmetric transition metal catalysis. But for some types of reactions, the enantioselectivity effect is not good, therefore, ligands with TADDOL and SPINOL chiral skeletons were developed. At present, when looking for ligands or catalysts for asymmetric reactions, BINOL and SPINOL derivatives are usually screened at the same time. Axichiral BINOL and SPINOL compounds have been widely used in the field of asymmetric catalysis, however, it is still necessary to explore axichiral ligands with novel structural frameworks. [0003] Contents of the invention [0004] The functionalization of alkynes is one of the effective methods to construct alkenes, and th...

Claims

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Application Information

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IPC IPC(8): C07C39/225C07C39/40C07C43/23C07C47/57C07C69/18C07C69/94C07C37/14C07C41/30C07C45/69C07C67/347C07F9/6574C07F9/6571
CPCC07C39/225C07C39/40C07C43/23C07C47/57C07C69/18C07C69/94C07F9/65744C07F9/657154C07B2200/13C07B2200/07
Inventor 谭斌王永彬张健吴权昊
Owner SOUTH UNIVERSITY OF SCIENCE AND TECHNOLOGY OF CHINA
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