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High-optical-activity axial chirality allene compound and construction method thereof

A technology of optical activity and construction method, which is applied in the field of highly optically active axial chiral allene compounds and their construction, can solve the problems of reduction, etc., and achieve the effect of simple raw materials, excellent stereoselectivity and high stereoselectivity

Active Publication Date: 2018-12-11
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Large hindered groups (such as tert-butyl, etc.) are very special functional groups, and their existence will reduce the application possibility of 1,3-disubstituted axial chiral allene products

Method used

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  • High-optical-activity axial chirality allene compound and construction method thereof
  • High-optical-activity axial chirality allene compound and construction method thereof
  • High-optical-activity axial chirality allene compound and construction method thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032]

[0033] Wherein, equiv means equivalent weight, mol means mole, THF means tetrahydrofuran, and ee means enantiomeric excess percentage.

[0034]In the glove box, sequentially add K to a dry Schlenk reaction tube 2 CO 3 (276.2 mg, 2 mmol) and (R)-(-)-DTBM-SEGPHOS (70.5 mg, 0.06 mmol). Remove the reaction tube from the glove box, then add [Pd(π-cinnamyl)Cl] under nitrogen protection 2 (13.2 mg, 0.025 mmol) and 2a (263.8 mg, 2 mmol) / THF (3.5 mL). After the reaction tube was stirred and reacted at 25°C for 30 minutes, it was placed in an ice machine at 5°C and stirred for another 10 minutes. Then 1a (226.2 mg, 1 mmol) / THF (1.5 mL) was added under nitrogen protection with stirring. After the reaction mixture was stirred at 5° C. for 26 hours, the reaction was completed as monitored by thin layer chromatography (TLC). Filter through a short column of silica gel and rinse with ethyl acetate (10 mL×3). Concentrate the resulting filtrate, and use silica gel column flas...

Embodiment 2

[0036]

[0037] Operation is with embodiment 1. [Pd(π-cinnamyl)Cl] 2 (2.7mg, 0.005mmol), (R)-(-)-DTBM-SEGPHOS (14.5mg, 0.012mmol), K 2 CO 3 (55.5mg, 0.4mmol), 1b (28.5mg, 0.2mmol) / THF (0.5mL) and 2a (52.6mg, 0.4mmol) / THF (1.5mL) were reacted to give oily allene product (R a )-3ba (30.7mg, 77%) (eluent: petroleum ether (60-90 ° C) / ethyl acetate = 30 / 1): 90% ee (HPLC conditions: Chiralcel OD-Hcolumn, n-hexane / i -PrOH=200 / 1,0.5mL / min,λ=214nm,t R (minor) = 23.4min,t R (major)=24.8min); [α] D 20 =-40.9 (c=0.47, CHCl 3 ); 1 H NMR (300MHz, CDCl 3 )δ5.19-5.04(m, 2H, CH=C=CH), 3.750(s, 3H, OCH 3 ),3.745(s,3H,OCH 3 ), 3.52(t, J=7.5Hz, 1H, CH), 2.62-2.53(m, 2H, CH 2 ),1.62(dd,J 1 =6.8Hz,J 2 =3.5Hz,3H,CH 3 ); 13 C NMR (75MHz, CDCl 3 )δ204.8169.4, 169.3, 87.6, 86.8, 52.5, 51.1, 27.8, 14.3; IR (neat, cm -1 )2987,2954,2919,2855,1966,1751,1739,1436,1341,1232,1152,1043; MS(EI,70eV)m / z(%)199(M + +1,3.74),198(M + ,27.55),98(100); HRMS calcd.for C 10 h 14 o 4 [M + ]:1...

Embodiment 3

[0039]

[0040] Operation is with embodiment 1. [Pd(π-cinnamyl)Cl] 2 (13.2mg, 0.025mmol), (R)-(-)-DTBM-SEGPHOS (71.2mg, 0.06mmol), K 2 CO 3 (276.6mg, 2mmol), 1c (169.5mg, 1mmol) / THF (1.0mL) and 2a (264.3mg, 2mmol) / THF (4.0mL) were reacted to give the oily allene product (R a )-3ca (205.6mg, 91%) (eluent: petroleum ether (30-60 ℃) / ethyl acetate = 50 / 1): 91% ee (HPLC conditions: Chiralcel AD-H column, n-hexane / i-PrOH=100 / 1,0.7mL / min,λ=214nm,t R (major) = 15.8min,t R (minor)=16.7min); [α] D 20 =-62.9 (c=1.00, CHCl 3 )); 1 H NMR (300MHz, CDCl 3 )δ5.20-5.06(m, 2H, CH=C=CH), 3.75(s, 6H, 2×OCH 3 ), 3.52(t, J=7.5Hz, 1H, CH), 2.62-2.54(m, 2H, CH 2 ),1.98-1.88(m,2H,CH 2 ),1.48-1.33(m,2H,CH 2 ),0.92(t,J=7.1Hz,3H,CH 3 ); 13 C NMR (75MHz, CDCl 3 )δ203.9, 169.4, 169.3, 92.7, 87.2, 52.5, 51.1, 30.8, 27.9, 22.2, 13.6; IR (neat, cm -1 )2957,2933,2873,2847,1964,1755,1738,1436,1339,1269,1232,1154,1079,1040; MS(EI,70eV)m / z(%)226(M + ,12.48),79(100); HRMS calcd.for C 12 h ...

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Abstract

The invention relates to a high-optical-activity axial chirality allene compound and a construction method thereof. The construction method is a method for directly constructing an allene compound with axial chirality under the high stereoselectivity by performing a reaction of 2,3-allene functional group compound and a nucleophilic reagent in an organic solvent under the action of a palladium catalyst, a chiral diphosphine ligand and alkali. The method has the advantages of simplicity for operation, easiness for obtaining raw materials and a reagent and the like; the substrate universality iswide; high stereoselectivity of the product is very excellent (90 to 96%ee). The high-optical-activity allene product obtained by the method disclosed by the invention is used as an important intermediate and can be used for constructing chiral compounds, such as gamma-allenoate, gamma-allenoic acid, gamma-allenol and gamma-butyrolactone, and gamma-butyrolactone natural product (R)-traumatic lactone (98%ee) is synthesized under high enantioselectivity for the first time.

Description

technical field [0001] The invention relates to a compound and its chemical synthesis method, in particular to a highly optically active axial chiral allene compound and its construction method. Background technique [0002] In the past two decades, allene chemistry has made great progress and has become a very important branch of organic chemistry. Unlike alkenes and alkynes, allenes have axial chirality. 1,3-disubstituted axial chiral allene structural units exist in many natural products and drug molecules; at the same time, 1,3-disubstituted axial chiral allene can also be used as a key intermediate for important biological and chemical activities Synthesis of natural products (Ref: (a) A.; Krause, N. Angew. Chem. Int. Ed. 2004, 43, 1196. (b) Ogasawara, M.; Nagano, T.; Hayashi, T. J. Org. Chem. 2005, 70, 5764. (c) Crouch, I.T.; Neff, R.K.; Frantz, D.E.J. Am. Chem. Soc. 2013, 135, 4970. (d) Tang, X.; Huang, X.; Cao, T.; Han, Y.; Jiang, X. ; Lin, W.; Tang, Y.; Zhang, ...

Claims

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Application Information

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IPC IPC(8): C07C67/343C07C69/602C07C69/734C07C69/608C07C51/09C07C59/42C07C59/64C07D307/33
CPCC07C51/09C07C59/42C07C59/64C07C67/343C07C69/602C07C69/608C07C69/734C07D307/33C07C2601/14C07B2200/07
Inventor 麻生明宋世铧周静傅春玲
Owner ZHEJIANG UNIV
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