High optical activity allene compound combing axial chirality and central chirality, construction method and application thereof

An optically active, axial chiral technology, applied in the field of direct construction of highly optically active allene compounds with both axial chirality and central chirality

Inactive Publication Date: 2017-12-19
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, using this strategy to construct allene compounds with multiple chiral centers with high enantioselectivity still faces great challenges.

Method used

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  • High optical activity allene compound combing axial chirality and central chirality, construction method and application thereof
  • High optical activity allene compound combing axial chirality and central chirality, construction method and application thereof
  • High optical activity allene compound combing axial chirality and central chirality, construction method and application thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044]

[0045] Wherein, equiv means equivalent weight, mol means mole, d.r. means diastereomer ratio, NMP means N-methylpyrrolidone, and ee means enantiomeric excess percentage.

[0046] In the glove box, sequentially add [Pd(π-cinnamyl)Cl] to a dry Schlenk reaction tube 2 (0.0134g, 0.025mmol), chiral bisphosphine ligand (R)-L5a (0.0709g, 0.06mmol), and K 2 CO 3 (0.2763g, 2mmol). Then NMP (5mL) was added under the protection of nitrogen, and the reaction tube was placed in an oil bath preheated to 30°C. After stirring for 30 minutes, the reaction tube was removed from the oil bath, and 2,3- Allenyl acetate (R a *,S*)-1a (0.2781 g, 1 mmol) with NMP (5 mL), diphenylsulfonylmethane 2a (0.6105 g, 2 mmol). The reaction tube was placed in a 30°C oil bath again, stirred, and the reaction was completed after 12 hours by thin layer chromatography (TLC). Ethyl acetate (30 mL) was added to dilute the reaction, and the resulting mixture was washed with brine (20 mL×3). The orga...

Embodiment 2

[0048]

[0049] Operation is with embodiment 1. [Pd(π-cinnamyl)Cl] 2 (0.0134g, 0.025mmol), (R)-L5a (0.0709g, 0.06mmol), K 2 CO 3 (0.2762g, 2mmol), NMP (5mL), (R a *,S*)-1b(0.3330g, 1 mmol) / NMP(5mL) and bis(phenylsulfonyl)methane(2a)(0.6105g, 2mmol) were reacted for 12 hours. Flash column chromatography (eluent: petroleum ether (30~60°C) / ethyl acetate=8 / 1) gave oily chiral allene product (R a ,S)-3ba(0.3990g,70%):98%ee(HPLC conditions:Chiralcel OZ-H column, n-hexane / i-PrOH=90 / 10,1.0mL / min,λ=214nm,t R (major) = 21.5min,t R (minor) = 48.7min); [α] D 20 =-78.5 (c=0.995, CHCl 3 ); 1 H NMR (300MHz, CDCl 3 )δ7.94(d, J=7.5Hz, 2H, ArH), 7.88(d, J=7.2Hz, 2H, ArH), 7.66(t, J=7.4Hz, 2H, ArH), 7.59-7.42(m , 4H, ArH), 5.91-5.72(m, 1H, =CH), 5.49-5.36(m, 1H, =CH), 5.12(td, J 1 =6.2Hz,J 2 =2.0Hz, 1H, =CH), 5.06-4.87(m, 2H, =CH 2 ), 4.66(d, J=1.8Hz, 1H, CH), 3.09-2.94(m, 1H, CH), 2.04(q, J=7.0Hz, 2H, CH 2 ),1.97-1.52(m,8H,5H from Cy,CH 2 , and CH),1.48-0.79(m,17H,5H from Cy ...

Embodiment 3

[0051]

[0052] Operation is with embodiment 1. [Pd(π-cinnamyl)Cl] 2 (0.0134g, 0.025mmol), (R)-L5a (0.0710g, 0.06mmol), K 2 CO 3 (0.2762g, 2mmol), NMP (5mL), (R a *,S*)-1c(0.2521g, 1 mmol) / NMP(5mL) and bis(phenylsulfonyl)methane(2a)(0.6105g, 2mmol) were reacted for 17 hours. Flash column chromatography (eluent: petroleum ether (30~60°C) / ethyl acetate=8 / 1) gave oily chiral allene product (R a ,S)-3ca(0.3428g,70%):97%ee(HPLC conditions:Chiralcel OZ-H column, n-hexane / i-PrOH=80 / 20,1.0mL / min,λ=214nm,t R (major) = 17.8min,t R (minor) = 31.2min); [α] D 20=-65.9 (c=1.05, CHCl 3 ); 1 H NMR (300MHz, CDCl 3 )δ 8.01-7.83(m,4H,ArH),7.73-7.59(m,2H,ArH),7.59-7.45(m,4H,ArH),5.44-5.32(m,1H,=CH),5.15(qd ,J 1 =6.6Hz,J 2 =2.1Hz,1H,=CH),4.67(d,J=1.5Hz,1H,CH),3.13-3.00(m,1H,CH),2.04-1.78(m,3H,1H from CH 2 and CH 2 ),1.77-1.61(m, 1H,1H from CH 2 ),1.50-1.00(m,12H,CH 2 ×6),0.97-0.79(m,6H,CH 3 ×2); 13 C NMR (75MHz, CDCl 3 )δ204.0, 140.1, 138.6, 134.3, 134.1, 129.4, 128.93, 128....

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Abstract

The invention discloses a method for directly constructing a high optical activity allene compound combing axial chirality and central chirality. Under effects of a palladium catalyst, a chiral diphosphine ligand and alkali, 2,3-allene function group compounds shown in a formula (1) and a nucleophilic reagent in a formula (2) are reacted in an organic solvent, and the high optical activity allene compound combing axial chirality and central chirality can be directly constructed by one step. The method has the advantages of simple operation, easy acquisition of raw material and the reagent, mild reaction condition, wide substrate universality, and good function group compatibility, and the stereoselective performance of the product is excellent (greater than 99:1 d.r., 95-greater than 99% ee). The high optical activity allene compound can be taken as an important intermediate for constructing the compounds such as monofluoro methylation allene, gamma-allene acid ester, gamma-allene acid, gamma-allenol, and gamma-butanolide containing several chiral centers.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis, and in particular relates to a method for directly constructing a highly optically active allene compound with axial chirality and central chirality. Background technique [0002] As we all know, chiral phenomena widely exist in nature. The study of chirality has inspired human beings to re-understand chemistry, physics and life sciences. Chiral molecules can be divided into many types. In addition to the central chirality that has been widely studied, there are also axial chirality and planar chirality. Chiral molecules with different configurations may have different physical and chemical properties and physiological activities. Therefore, how to efficiently construct chiral molecules is an extremely important part of stereochemical research. Today, although people have made great progress in how to construct molecules containing only one kind of chiral center, how to efficiently c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07B53/00C07D307/33C07F7/18C07C315/04C07C317/14C07C67/343C07C69/608C07C69/73C07C17/361C07C22/00C07C67/32C07C51/09C07C57/26C07C29/147C07C33/14
CPCC07B53/00C07B2200/07C07C17/361C07C29/147C07C51/09C07C67/32C07C67/343C07C315/04C07D307/33C07F7/1804C07C317/14C07C69/608C07C69/73C07C22/00C07C57/26C07C33/14
Inventor 麻生明戴健鑫段鑫宇傅春玲
Owner ZHEJIANG UNIV
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