有机催化串联反应合成吡咯并[1,2-a](异)喹啉化合物

Synthesis of Pyrrolo[1,2-a](iso)Quinoline Compounds by Organocatalyzed Tandem Reactions

发展了一种“一锅法”有机催化串联反应用于合成吡咯并[1,2-a](异)喹啉产物,以2-(喹啉-2-基)乙酸乙酯、α,β-不饱和醛为原料,在二级胺催化作用下发生Michael加成反应,在N-杂环卡宾接力催化下发生喹啉氮原子和醛的α位之间的环加成反应,再在氧气作用下进一步发生芳构化反应合成一系列吡咯并[1,2-a](异)喹啉产物。结果表明,喹啉环和不饱和醛的苯环上不同位置的取代基对反应的产率没有太大影响,该反应也适用于异喹啉乙酸乙酯和喹喔啉乙酸乙酯底物的合成。

A metal-free catalytic “one-pot ” synthesis for a biologically relevant molecular architecture,pyrrolo[1,2-α](iso)quinolines, is developed. Based on our previous studies on the synthesis of indolizines and imidazopyridines, the key reaction involved in this study is promoted by an amine and N-heterocyclic carbene(NHC)relay catalysis via Michael addition-[3+2] cycloaddition of azaarenes and α,β-unsaturated aldehydes. The reactions between azaarenes(0.2 mmol) and α,β-unsaturated aldehydes(0.4 mmol) are sequentially catalyzed by the amine(10%,mol fraction) and NHC catalyst(20%, mol fraction) in the presence of 4-dimethylaminopyridine(DMAP) as the base(0.1 mmol) and(diacetoxyiodo)benzene(PIDA) as the oxidant(0.3 mmol) in toluene at room temperature. The first Michael addition step is catalyzed by the amine catalyst for 4 h at room temperature to give the Michael-addition product. Without any further work-up, NHC catalyst, DMAP and PIDA are added into the solution for an additional 18 h at room temperature. In this latter step, cycloaddition and aromatization takes place to give pyrrolo[1,2-α]quinoline products. The “one-pot” reactions proceed smoothly for a variety of substituted and more conjugated quinolines, including those with tethered neutral, electron-withdrawing and electron-donating groups at 4, 6, 7-positions of quinolines. Ethyl 2-(benzo[f]quinolin-3-yl)acetate also tolerates the reaction condition to afford the quinoline product in 75% yield. The substitution of the α,β-unsaturated aldehyde structures with electron-donating and withdrawing groups on the phenyl ring also successfully produces the corresponding quinoline products in moderate-to-good yields. Moreover, isoquinoline is also tolerated to give the corresponding isoquinoline product in 72% yield. Hetero quinoline-ethyl 2-(quinoxalin-2-yl)acetate also works well to afford ethyl 1-formyl-2-phenylpyrrolo[1,2-α]quinoxaline-3-carboxylate in 56% yield.