synthesisoftetrahydropyrroloindolo12apyrazinesbyenantioselectivehydrogenationofheterocyclicimines

	synthesisoftetrahydropyrroloindolo12apyrazinesbyenantioselectivehydrogenationofheterocyclicimines
	Hu SB(胡书博); Chen MW(陈木旺); Zhai XY(翟小勇); Zhou YG(周永贵)
刊名	actachimicasinica
	2018-01-01
卷号	76 期号:2 页码:103
ISSN号	0567-7351
英文摘要	1,2,3,4-Tetrahydropyrrolo1,2-apyrazines are an important motif due to their biological activities and widely existing in natural products. Notably, the substituent and the absolute configuration are important for the medicinal efficacy. Thus, the synthesis of chiral tetrahydropyrrolo1,2-apyrazines has attracted much attention of scientists. Most synthetic methods utilized chiral starting materials or auxiliaries. Kinetic resolution was an alternative way to give chiral tetrahydropyrrolo 1,2-apyrazines. The first catalytic asymmetric synthetic method was developed in 2011 by Li and Antilla through a chiral phosphoric acid-catalyzed asymmetric intramolecular aza-Friedel-Crafts reaction of aldehydes with N-aminoethylpyrroles in high enantiocontrol level. Subsequently, the sequential aerobic oxidation-asymmetric intramolecular aza-Friedel-Crafts reaction between N-aminoethylpyrroles and benzyl alcohols for the synthesis of tetrahydropyrrolo 1,2-apyrazines was realized using chiral bifunctional heterogeneous materials composed of Au/Pd nanoparticles and chiral phosphoric acids. The asymmetric hydrogenation as an efficient way has been successfully applied to synthesize the kind of chiral amines. In 2012, Our group achieved the asymmetric hydrogenation of 1-substituted pyrrolo1,2-apyrazines via a substrate activation strategy. Recently, we reported the direct asymmetric hydrogenation of 3-substituted pyrrolo1,2-apyrazines in up to 96% ee values. Considering their impressive significance, herein, we successfully hydrogenated 3,4-dihydropyrrolo1,2-apyrazines and 3,4-dihydroindolo1,2-apyrazines with up to 99% yield and 95% ee. The reaction features mild condition, high enantioselectivity and high atom-economy. The typical procedure for asymmetric hydrogenation is as follows: A mixture of Ir(COD) Cl(2) (3.0 mg, 0.0045 mmol) and the ligand Cy-WalPhos (6.6 mg, 0.0099 mmol) was stirred in toluene (1.0 mL) at room temperature for 5 min in the glove box. Then the solution was transferred to the vial containing the substrate 3,4-dihydropyrrolo1,2-apyrazines (0.3 mmol) together with toluene (2.0 mL). The vial was taken to an autoclave and the hydrogenation was conducted at 40. as well as at a hydrogen pressure of 500 psi for 48 h. After carefully releasing the hydrogen, the autoclave was opened and the toluene was evaporated in vacuo. The residue was purified by column chromatography to afford the corresponding chiral tetrahydropyrrolo1,2-apyrazines.
资助项目	[National Natural Science Foundation of China] ; [Chinese Academy of Sciences] ; [Dalian Bureau of Science and Technology]
语种	英语
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/178497]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
作者单位	中国科学院大连化学物理研究所
推荐引用方式 GB/T 7714	Hu SB,Chen MW,Zhai XY,et al. synthesisoftetrahydropyrroloindolo12apyrazinesbyenantioselectivehydrogenationofheterocyclicimines[J]. actachimicasinica,2018,76(2):103.
APA	胡书博,陈木旺,翟小勇,&周永贵.(2018).synthesisoftetrahydropyrroloindolo12apyrazinesbyenantioselectivehydrogenationofheterocyclicimines.actachimicasinica,76(2),103.
MLA	胡书博,et al."synthesisoftetrahydropyrroloindolo12apyrazinesbyenantioselectivehydrogenationofheterocyclicimines".actachimicasinica 76.2(2018):103.