不对称氢化杂环亚胺合成四氢吡咯/吲哚[1,2-a]并吡嗪  

Synthesis of Tetrahydropyrrolo/indolo[1,2-a]pyrazines by Enantioselective Hydrogenation of Heterocyclic Imines

作　　者：胡书博 陈木旺[1] 翟小勇 周永贵[1] 

机构地区：[1]中国科学院大连化学物理研究所,大连116023 [2]中国科学院大学,北京100049

出　　处：《化学学报》2018年第2期103-106,共4页Acta Chimica Sinica

基　　金：国家自然科学基金(Nos.21532006;21690074);中国科学院前沿科学项目(No.QYZDJ-SSW-SLH035);大连市科技局(No.2016RD07)资助~~

摘　　要：报道了一种铱催化3,4-二氢吡咯并吡嗪和3,4-二氢吲哚[1,2-a]并吡嗪的不对称氢化合成相应的1,2,3,4,-四氢吡咯/吲哚[1,2-a]并吡嗪化合物的方法.该催化体系适用于芳基取代的底物和烷基取代的底物,反应收率高达99%,对映选择性过量值最高为95%.该反应操作简单,原子经济性好.1,2,3,4-Tetrahydropyrrolo[1,2-a]pyrazines 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 tetrahydropyrrolo[1,2-a]pyrazines 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-a]pyrazines. 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 tetrahydro- pyrrolo[ 1,2-a]pyrazines 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 pyrrolo[1,2-a]pyrazines via a substrate activation strategy. Recently, we reported the direct asymmetric hydrogenation of 3-substituted pyrrolo[1,2-a]pyrazines in up to 96% ee values. Considering their impressive significance, herein, we successfully hydrogenated 3,4-dihydropyrrolo[1,2-a]pyrazines and 3,4-dihydroindolo[1,2-a]pyrazines with up to 99% yield and 95% ee. The reaction features mild condition, high enantioselectivity and high atom-economy. The typical procedure for asymmetric hydro- genation 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

关 键 词：不对称氢化 杂环亚胺 四氢吡咯/吲哚[1 2-a]并吡嗪 

分 类 号：O626[理学—有机化学]