Method for synthesizing indole terpene analogue through Heck cascade reaction

A tandem reaction and indole terpene technology, applied in chemical instruments and methods, compounds of group 4/14 elements of the periodic table, organic chemistry, etc., to achieve high enantioselectivity of products

Active Publication Date: 2021-10-22
HENAN NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006]Construct the indole skeleton by Heck cyclization reaction, construct the chiral cyclic terpene skeleton by asymmetric dearomatization reaction, realize the chiral indole terpene skeleton in one step Construction strategies have not been reported yet

Method used

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  • Method for synthesizing indole terpene analogue through Heck cascade reaction
  • Method for synthesizing indole terpene analogue through Heck cascade reaction
  • Method for synthesizing indole terpene analogue through Heck cascade reaction

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Taking 1,3-dimethyl-2-naphthol 1a and N-2-iodophenyl-N-Ts-allenamine 2a to generate 3aa as an example, the reaction conditions are optimized, and the reaction equation is as follows:

[0033]

[0034]

[0035]

[0036] a Unless otherwise specified, the reaction steps are as follows: 1a (0.1mmol), 2a (0.12mmol), [Pd(C 3 h 5 )Cl] 2 (xmol%), ligand (y mol%), base (1.5equiv), 1.0mL solvent, in N 2 React under protection at T°C for 12 hours. b separation yield, c Determination by chiral high performance liquid chromatography. d 3aa yields and ee values ​​were isolated after recrystallization.

[0037]During the screening of reaction conditions, the effect of the ligand on the reaction was first investigated (entries 1-5). At the same time, the effects of different solvents, reaction temperature (-20°C to +25°C), ligand L, palladium catalyst ratio and different bases (such as potassium carbonate, cesium carbonate, etc.) on the reaction were investigated, and L...

Embodiment 2

[0040]

[0041] Under nitrogen protection, in a Schlenk tube equipped with a magneton, 1-methyl-3-ethyl-β-naphthol (0.1 mmol), N-2-iodophenyl-N-Ts-allenamine (0.11 mmol), [Pd(C 3 h 5 )Cl] 2 (1mol%), L5 (1mol%) and Cs 2 CO 3 (0.15mmol), sealed with a rubber stopper. Syringe 1.0 mL of dry toluene into the reaction tube. The reaction tube was placed at 0°C and stirred overnight. The reaction solution was quickly passed through a short silica gel column, eluting with dichloromethane / methanol = 15 / 1, and the solution was concentrated in vacuo to obtain a crude product. Purification by silica gel column chromatography gave 3ba as a yellow solid with a yield of 91% and 93% ee. 1 H NMR (600MHz, CDCl 3 )δ7.81(d, J=7.8,1H),7.49-7.44(m,2H),7.41(d,J=7.2Hz,1H),7.34(td,J=7.2,1.2Hz,1H),7.29 (td,J=7.8,1.8Hz,1H),7.22(d,J=7.8Hz,1H),7.20-7.13(m,4H),7.12-7.07(m,1H),6.87(s,1H), 6.45(s,1H),3.50(d,J=14.3Hz,1H),3.07(d,J=14.3Hz,1H),2.34(s,3H),2.20-2.12(m,1H),2.10-2.02 (m,1H),1.59(s,3H),0...

Embodiment 3

[0043]

[0044] Under nitrogen protection, in a Schlenk tube equipped with a magneton, 1-methyl-3-allyl-β-naphthol (0.1 mmol), N-2-iodophenyl-N-Ts-allenamine ( 0.11mmol), [Pd(C 3 h 5 )Cl] 2 (1mol%), L5 (1mol%) and Cs 2 CO 3 (0.15mmol, 1.5 equivalents), sealed with a rubber stopper. Syringe 1.0 mL of dry toluene into the reaction tube. The reaction tube was placed at 0°C and stirred overnight. The reaction solution was quickly passed through a short silica gel column, eluting with dichloromethane / methanol = 15 / 1, and the solution was concentrated in vacuo to obtain a crude product. Then purified by silica gel column chromatography, the yellow oil 3ca was obtained with a yield of 91%, 92% ee. 1 H NMR (400MHz, CDCl 3 )δ7.82(d, J=8.0Hz, 1H), 7.51-7.45(m, 2H), 7.43(d, J=7.6Hz, 1H), 7.37(td, J=7.2, 1.2Hz, 1H), 7.30(td,J=7.6,1.6Hz,1H),7.25-7.17(m,2H),7.18-7.12(m,3H),7.10(td,J=7.6,1.1Hz,1H),6.82(s, 1H),6.43(s,1H),5.55-5.20(m,1H),4.95-4.72(m,2H),3.49(d,J=14.0Hz,1H),3.07(d,...

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Abstract

The invention discloses a method for synthesizing an indole terpene analogue through Heck / dearomatization cascade reaction, and belongs to the technical field of organic chemistry. Substituted 2-naphthol and N-substituted phenyl allene amine are used as raw materials, and in the presence of a palladium catalyst and a chiral phosphoramidite ligand, Heck / dearomatization cascade reaction is performed to obtain the indole terpene analogue. The method has the advantages of good chemical selectivity and enantioselectivity and high yield, and the product contains a chiral quaternary carbon center.

Description

technical field [0001] The invention relates to a method for synthesizing indoleterpene analogues through Heck series reactions, and belongs to the technical field of asymmetric synthesis in organic chemistry. Background technique [0002] Indole terpenoids are an important class of natural products with a wide range of biological activities. At present, there are two main strategies for the chemical synthesis of indole terpenoids: one is the coupling strategy of cyclic terpenoids and indole. For example, Li Ang uses a chiral raw material and an indole Grignard reagent for carbonyl addition to obtain an intermediate, and then undergoes intramolecular cyclization and deprotection to obtain the natural product xiamycin A (formula a); Sarpong uses an indole lithium reagent to add a chiral compound Synthesized the natural product xiamycin A (formula b); Dethe reported the synthesis of mycoleptodiscin A (formula c) through the coupling strategy of cyclic terpene and indole. [...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/12C07F7/10
CPCC07D209/12C07F7/083
Inventor 王东超杨婷婷郭海明吴盼盼成鹏鹏渠桂荣
Owner HENAN NORMAL UNIV
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