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Chiral vicinal diamine derivative and catalytic asymmetric synthesis method thereof

A technology of chiral phosphoric acid and compounds, applied in organic chemistry methods, organic chemistry, etc., can solve problems such as unfavorable amine conversion, easy oxidation of alkylamines, poisoning of transition metal catalysts, etc., achieve mild reaction conditions, wide substrate range, Effect of excellent functional group tolerance

Active Publication Date: 2017-10-17
SOUTH UNIVERSITY OF SCIENCE AND TECHNOLOGY OF CHINA
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AI Technical Summary

Problems solved by technology

On the one hand, the high affinity of strong Lewis basic alkylamines for transition metals may lead to the formation of stable amine-metal complexes, leading to the poisoning of transition metal catalysts.
On the other hand, unprotected alkylamines are susceptible to oxidation under oxidative diamination reaction conditions
Therefore, diamination of unactivated alkenes often requires appropriate electron-withdrawing protecting groups to suppress strong affinity and amine oxidation, leading to the indirect use of these methods for free amine synthesis but disadvantageous for subsequent amine transformations.

Method used

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  • Chiral vicinal diamine derivative and catalytic asymmetric synthesis method thereof
  • Chiral vicinal diamine derivative and catalytic asymmetric synthesis method thereof
  • Chiral vicinal diamine derivative and catalytic asymmetric synthesis method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Synthesis of 1m

[0051] S-1m can be carried out according to the steps reported in literature 2.

[0052]

[0053] At 0°C, to the stirred S-1m (2.0mmol) and iPr 2 Anhydrous CH of NEt (2.0mmol) 2 Cl 2 (4.0 mL) to the solution was slowly added 1-isocyanato-3,5-bis(trifluoromethyl)-benzene (2.0 mmol). The reaction mixture was then warmed to room temperature and stirred for 1 hour. After complete conversion (monitored by TLC), the crude mixture was chromatographed on a silica gel column (eluent: petroleum ether / CH 2 Cl 2 = 100 / 1 to 1 / 2, first remove CH with 100% petroleum ether 2 Cl 2 for loading) was directly purified to afford lm (1.72 mmol, 86% yield).

[0054] 1 H NMR (500MHz, CDCl 3 )δ7.70(s,3H),7.41(s,1H),7.34(dd,J=5.0,3.5Hz,2H),7.31–7.26(m,2H),7.26–7.20(m,1H),5.49 (s,1H),5.25(d,J=0.5Hz,1H),5.01(d,J=1.0Hz,1H),3.23(dd,J=13.0,7.5Hz,2H),2.51(t,J= 7.5Hz, 2H), 1.73–1.59(m, 2H).

[0055] 13 C NMR (125MHz, CDCl 3 )δ155.6, 147.3, 140.7, 140.5, 132.3 (q, J =...

Embodiment 2

[0059] Synthesis of 1n and 1l

[0060] S-1n-1 and S-1o-1 can be based on literature 3 ( C.; Hennecke, U.Org.Lett.2015, 17, 3226) reported steps.

[0061]

[0062] At 0°C, to S-1n-1 (0.57g, 3.0mmol), phthalimide (0.44g, 3.0mmol) and PPh 3 (0.79 g, 3.0 mmol) in 20.0 mL of THF was added diethyl azodicarboxylate (0.5 mL, 3.0 mmol). The mixture was warmed to room temperature for 18 hours, the solvent was extracted and purified by silica gel column chromatography (eluent: petroleum ether / EtOAc=20:1~5:1) to give S-1n-2 (0.8 g, 83%) .

[0063] To a solution of S-ln-2 (0.64 g, 2.0 mmol) in EtOH (15.0 mL) was added hydrazine monohydrate (0.4 mL, 6.0 mmol) at room temperature. The reaction mixture was stirred and heated to reflux for 2 hours. After cooling to room temperature, the mixture was filtered and the filtrate was concentrated in vacuo to give the crude amine which was used in the next step without purification.

[0064] 1n and 1l were obtained by a similar procedure to...

Embodiment 3

[0080] Synthesis of 1w and 1x

[0081]

[0082] S-1w can be performed according to the steps reported in Document 1 and Document 2.

[0083] To a solution of S-1w (12.0 mmol) in toluene (24.0 mL) were added neopentyl glycol (36.0 mmol) and PPTS (1.98 mmol) under argon protection. The reaction was then stirred at 100°C for 18 hours. After complete conversion (monitored by TLC), the reaction mixture was extracted with EtOAc. The combined organic phases were concentrated in vacuo. The residue was purified by silica gel column chromatography (petroleum ether / EtOAc=20 / 1) to give S-1x (10.8 mmol, 90% yield).

[0084] At 0°C, to LiAlH 4 (456.0 mg, 12.0 mmol) of Et 2 O (36.0mL) suspension was slowly added S-1x (6.0mmol) of Et 2 O (4.0 mL) solution. The mixture was then warmed to room temperature and stirred for 3 hours. At 0°C, water (1 mL) and Na 2 SO 4 (8.0 g) to quench the reaction. The reaction mixture was allowed to warm to room temperature, stirred for an additiona...

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Abstract

The invention discloses a chiral vicinal diamine derivative. The chiral vicinal diamine derivative is a compound as shown in a formula I, or tautomer, enantiomer and diastereoisomer thereof, wherein Ar1 and Ar2 are selected from aryl and ceteroary respectively; the aryl and ceteroary do not have substituent group or have one or more substituent groups; R1 is selected from hydrogen, alkyl, phenyl, esteryl and methylene; when R1 is methylene, an A ring is formed through 0 to 5 methylene; X is selected from N3, NH2, NHBoc and N(Bn)2; B rings are 4 to 7 saturated or unsaturated heterocyclic rings; M is carbon or nitrogen; when M is carbon, G is selected from hydrogen, alkyl, alkoxy and esteryl; when M is nitrogen, G is selected from Ms, Ts, Boc and Bn. The invention further discloses a catalytic asymmetric synthesis method of the chiral vicinal diamine derivative. The method has a wide substrate range, excellent functional group tolerance and mild reaction conditions, is high in yield and good in enantioselectivity, and belongs to a convenient and practical method.

Description

technical field [0001] The invention relates to a chiral vicinal diamine derivative and a catalytic asymmetric synthesis method thereof. Background technique [0002] Chiral vicinal diamines are the key structures of many natural products, pharmaceuticals and agrochemicals, and they are also good synthetic units for the development of chiral ligands, organic catalysts and auxiliary agents widely used in asymmetric synthesis. Therefore, the assembly of vicinal diamines from readily available precursors has always been one of the important goals in the field of organic synthesis. [0003] Among them, the catalytic asymmetric diamination of unactivated alkenes with transition metal or aryl iodide catalysts is a straightforward and very attractive approach to obtain such useful vicinal diamine scaffolds, with alkenes readily available as starting materials. However, the amines introduced by these asymmetric catalytic systems must have electron-withdrawing protecting groups, and...

Claims

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Application Information

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IPC IPC(8): C07D207/09C07D209/54C07D207/16C07D405/10
CPCC07B2200/07C07D207/09C07D207/16C07D209/54C07D405/10
Inventor 刘心元王福利董晓阳林进顺
Owner SOUTH UNIVERSITY OF SCIENCE AND TECHNOLOGY OF CHINA
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