酰氯的Schmidt反应制备芳并吡咯里西啶

Preparation of Aryl Fused Pyrrolizidines via Intramolecular Schmidt Reaction of Acyl Chlorides with Alkyl Azides

主要开展了烷基叠氮参与的分子内酰氯的Schmidt反应研究,合成了13种芳基取代的叠氮羧酸,并对其进行Schmidt重排反应研究.通过草酰氯原位活化反应底物中的羧基,将其转化为酰氯单元,提升其与叠氮基团的反应能力.通过底物结构的设计,使得重排反应主要经历异氰酸盐阳离子中间体,进而被芳环亲核捕获.芳环带强供电子基团对该转化效率具有比较明显的影响:当羧基邻位为叔碳时,其反应效率很低;而当羧基邻位为季碳时,其反应则十分高效.研究人员对此现象进行分析,并提出了合理解释.通过酰氯的Schmidt重排反应,成功高效地合成了一系列的芳并吡咯里西啶产物.

The intramolecular Schmidt reaction of acyl chlorides with alkyl azides was explored. Thirteen aryl substituted azido carboxylic acids were prepared and applied to the Schmidt rearrangement. Activation of the carboxylic acids with oxalyl chloride generated the acyl chlorides in situ, which would enhance the reactivity of the carbonyl group. The intramolecular attack of azido group to the acyl chloride initiated the rearrangement, and the isocyanate ion intermediate was obtained from the migration with the designed substrates. Finally, the nucleophilic addition of aromatic ring to the isocyanate ion furnished the aryl fused pyrrolizidines. The substituents on the para-position of the aromatic ring would have obvious influence with the conversion. The azido carboxylic acid prepared from the ethyl p-methoxyphenylacetate, with a methine carbon attaching to the carbonyl group, gave the desired pyrrolizidine in very poor yield. Introducing an alkyl group to the methine carbon afforded the substrate with a quaternary carbon next to the carboxylic acid, and Schmidt reaction of such substrate could efficiently produce the aryl fused pyrrolizidine. The possible mechanism process was proposed to account for the different reactivity. In summary, a wide arrange of aryl fused pyrrolizidines were efficiently prepared from the intramolecular Schmidt reaction of acyl chlorides with alkyl azides followed by intramolecular capture of aryl rings to the isocyanate ion intermediates.