碳正离子Lewis酸催化氧化还原中性胺基α-C(sp^3)H芳基化反应  

Carbocation Lewis Acid Catalyzed Redox-Neutral α-C(sp^3)H Arylation of Amines

作　　者：张启超[1] 吕健[1] 罗三中[1] 

机构地区：[1]中国科学院化学研究所北京分子科学国家实验室分子识别与功能院重点实验室,北京100190

出　　处：《化学学报》2016年第1期61-66,共6页Acta Chimica Sinica

基　　金：国家自然科学基金(Nos.21390400;21202170;and 21472193);973项目(No.2012CB821600)~~

摘　　要：研究了碳正离子作为Lewis酸催化三组分氧化还原中性胺基α-C(sp3)-H芳基化反应.在温和条件下,三苯甲基溴和Na BArF原位生成的[Ph3C][BArF]可以高效、高化学选择性的催化四氢异喹啉、芳香醛和吲哚的氧化还原中性胺基α-C(sp3)-H芳基化反应(产率最高达99%).并且其它的亲核试剂(如:?-萘酚、3-甲氧基苯酚、3-N,N-二甲基胺基苯酚和2,5-二甲基吡咯等)也能较好的完成该反应.The α-substituted nitrogen-containing heterocycles（N-heterocycles） like tetrahydroisoquinolines（THIQs） and piperidines are common in nature and are present as the key functional group in bioactive and pharmacologically active compounds. The two traditional approaches for the synthesis of α-substituted N-heterocycles are Pictet-Spengler condensation and hydrogenation of the α-substituted cyclic imines. Recently, direct C（sp3）-H functionalization of N-heterocycles with various nucleophiles catalyzed by transition metal complex under the oxidants presents an atom-economic protocol without prior installation of activating group. However, new catalytic strategy or catalysts are still desirable in order to further address the use of excess oxidants and expensive transition metal complex. Stable carbocations, such as tritylium ions, have been widely used as organic Lewis acid catalysts and reagents in organic synthesis. In our studies, it was found that tritylium salts [Ph3C][BArF]（10 mol%） in situ generated by Ph3CBr（0.02 mmol） and Na BArF（0.02 mmol） could promote the three component redox-neutral α-arylation of amines reaction with tetrahydroisoquinoline 2（0.3 mmol）, aldehyde 3（0.2 mmol） and indole 4（0.3 mmol） in toluene（1.0 m L） to afford the desired α-substituted N-heterocyclic compounds 5 in good yields（up to 99% yield） at ambient temperature to 50 ℃. To our satisfaction, a variety of differently substituted indoles 4a^4i could work well with tetrahydroisoquinoline 2 and 2,6-dichlorobenzaldehyde 3a to provide the corresponding α-substituted N-heterocyclic compounds 5a^5i in good to excellent yields at room temperature. When other substituted benzaldehydes 3b^3f were used, the reactions could also proceed smoothly to give the compounds 5j^5o with moderate yield（up to 66% yield） at 50 ℃. Moreover, we have also developed redox-neutral α-arylation of tetrahydroisoquinoline 2 with other aromatic nucleophile such as substituted phenol, ？-naphthol and pyrrole un

关 键 词：碳正离子 LEWIS酸 氧化还原中性反应 α-C(sp3)H芳基化 有机催化 

分 类 号：O621.251[理学—有机化学]