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Method for catalytic synthesis of chiral propargylamine compound by chiral copper catalyst

A technology of chiral copper catalyst and propargyl amine is applied in the preparation of amino compounds, the preparation of organic compounds, the preparation of amino hydroxyl compounds, etc. small amount of effect

Inactive Publication Date: 2012-12-19
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although there have been some copper-catalyzed asymmetric substitution reactions of propargyl alcohol esters with amines [(a) Detz, R.J.; Delville, M.M.E.; Hiemstra, H.; Maarseveen, J.H.Angew.Chem.2008,120,3837 -3840.Angew.Chem.Int.Ed.2008,47,3777-3780.(b)Hattori,G.;Matsuzawa,H.;Miyake,Y.;Nishibayashi,Y.Angew.Chem.2008,120,3841 -3843.Angew.Chem.Int.Ed.2008,47,3781-3783.(c)Hattori,G.;Yoshida,A.;Miyake,Y.;Nishibayashi,Y.J.Org.Chem.2009,74,7603- 7607.(d) Hattori,G.;Sakata,K.;Matsuzawa,H.;Tanabe,Y.;Miyake,Y.;Nishibayashi,Y.J.Am.Chem.Soc.2010,132,10592-10608.(e) Hattori, G.; Miyake, Y.; Nishibayashi, Y. ChemCatChem. 2010, 2, 155-158. (f) Yoshida, A.; Hattori, G.; Miyake, Y.; 13,2460-2463.(g)Detz,R.J.;Abiri,Z.;Griel,R.;Hiemstra,H.;Maarseveen,J.H.Chem.Eur.J.2011,17,5921-5930.], but already The catalytic system usually cannot be applied to the amination reaction of propargyl alcohol esters involving primary and secondary amines at the same time. In addition, there is still a lot of room for improvement in the enantioselectivity of the reaction

Method used

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  • Method for catalytic synthesis of chiral propargylamine compound by chiral copper catalyst
  • Method for catalytic synthesis of chiral propargylamine compound by chiral copper catalyst
  • Method for catalytic synthesis of chiral propargylamine compound by chiral copper catalyst

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048]

[0049] Add metal precursor CuCl (0.015mmol, 5mol%) and chiral ligand L-3-1 (0.0165mmol, 5.5mol%) into the reaction flask, add 1 ml of anhydrous methanol under nitrogen protection, and stir at room temperature for 1 hour. Dissolve propargyl alcohol ester II-1 (0.3 mmol, 1 equiv), amine III-1 (0.36 mmol 1.2 equiv) and N,N-diisopropylethylamine (0.36 mmol 1.2 equiv) in 1 ml of anhydrous methanol, Then the solution was added into the above catalyst solution under the protection of nitrogen, and the reaction was stirred at room temperature for 12 hours. After the reaction was completed, rotary evaporation under reduced pressure and column separation gave colorless oily liquid I-1 (57.0 mg, 86% yield). The optical purity of I-1 by HPLC analysis was 95%ee.HPLC conditions: chiralcel OD-H, 40°C, 254nm, n-hexane / 2-propanol=95 / 5, flow rate=0.8mLmin -1 , major enantiomer: t 1 =5.59min;minor enantiomer:t 2 =6.37min.[α] D 20 =-11(c 0.7, CHCl 3 ); 1 H NMR (400MHz, CDCl 3 ...

Embodiment 2

[0051] II-1 in Example 1 is replaced by II-2, and all the other conditions are the same as in Example 1. To obtain 66.6mg of colorless oily liquid, 87% yield, 96%ee. HPLC conditions: chiralcel OD-H, 40°C, 254nm, n-hexane / 2-propanol=95 / 5, flow rate=0.8mLmin -1 , major enantiomer: t 1 =6.36min;minor enantiomer:t 2 =7.16min.[α] D 20 =+18(c 0.4,CHCl 3 ); 1 HNMR (400MHz, CDCl 3 ):δ=7.80(d,1H),7.42(d,1H),7.41-7.24(m,4H),7.06(d,2H),6.87(t,1H),5.98(s,1H),2.69( s,3H),2.51(s,1H)ppm; 13 C NMR (100MHz, CDCl 3 ):δ=149.7,135.1134.5,130.6,130.1,129.5,129.1,126.6,119.2,115.6,79.3,75.3,54.5,33.3ppm; HRMS calcd.for C 16 h 15 ClN[M+H]: 256.0893, found: 256.0893.

[0052]

Embodiment 3

[0054] II-1 in the embodiment is replaced by II-3, and all the other conditions are the same as in Example 1. 65.8 mg of colorless oily liquid was obtained, with a yield of 86%, and 97% ee. HPLC conditions: chiralcel OD-H, 40°C, 254nm, n-hexane / 2-propanol=95 / 5, flow rate=0.8mL / min, major enantiomer:t 1 =7.29min;minor enantiomer:t 2 =8.00min.[α] D 20 =4(c 0.5,CHCl 3 ); 1 H NMR (400MHz, CDCl 3 ):δ=7.60(s,1H),7.47-7.49(m,1H),7.33-7.29(m,4H),6.99-7.01(m,2H),6.87-6.91(m,1H),5.74(s ,1H),2.72(s,3H),2.57(s,1H); 13 C NMR (100MHz, CDCl 3 ):δ=149.8,140.1,134.5,129.7,129.2,128.0,127.6,125.6,119.3,115.5,79.1,75.4,56.2,33.8; HRMS calcd.for C 16 h 15 ClN[M+H]: 256.0893, found: 256.0891.

[0055]

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Abstract

The invention discloses a method for catalytic synthesis of a chiral propargylamine compound by a chiral copper catalyst. The method comprises the following steps that a copper salt and a chiral P, N, N-ligand undergo an in-suit reaction in the presence of an alcohol solvent to produce a chiral copper catalyst; and a propargyl compound and primary amine or secondary amine undergo a displacement reaction in the presence of the chiral copper catalyst to produce the chiral propargylamine compound. The method can realize convenient synthesis of various propargylamine compounds, and has the maximum yield of 92% and enantioselectivity (ee) of 97%. The method has simple processes, strong catalytic system universality and high enantioselectivity.

Description

technical field [0001] The invention relates to the field of preparing chiral propargyl amine compounds, in particular to a method for synthesizing chiral propargyl amine compounds catalyzed by a chiral copper catalyst. Background technique [0002] Chiral propargylamine compounds are an important class of organic synthons [Aschwanden, P.and Carreira E.M.; in Acetylene Chemistry: Chemistry, Biology and Material Science (Eds: F.Diederich, P.J.Stang and R.R.Tykwinski), WILEY- VCH, Weinheim, 2005, 101-138.]. Among the methods for synthesizing such compounds [(a) Cozzi, P.G.; Hilgraf, R.; Zimmermann, N. Eur. J. Org. Chem. 2004, 4095-4105. (b) Wei, C.-M. ; Li, Z.-G.; Li, C.-J. Synlett 2004, 1472-1483. (c) Zani, L.; Bolm, C. Chem. Commun. 2006, 4263-4275. (d) Blay, G.; Monleon, A.; Pedro, J.R. Curr. Org. Chem. 2009, 13, 1498-1539. (e) Trost, B.M.; Weiss, A.H. Adv. Synth. Catal. )Li,C.-J.Acc.Chem.Res.2010,43,581-590.], copper-catalyzed asymmetric synthesis occupies a very import...

Claims

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Application Information

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IPC IPC(8): C07B43/04C07B53/00C07C209/18C07C211/48C07C217/84C07C213/08C07C211/28C07C211/25C07D307/52C07F9/6518
Inventor 胡向平张成
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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