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Alkali-amide controlled selective synthesis of 7-azaindole and 7-azaindoline through domino reactions of 2-fluoro-3-methylpyridine and aldehydes†
Xinyu Xu,Mingjie Ou,Yan-En Wang,Tingzhi Lin,Dan Xiong,Fei Xue,Patrick J. Walsh,Jianyou Mao
Organic Chemistry Frontiers Pub Date : 03/24/2022 00:00:00 , DOI:10.1039/D2QO00339B
Abstract

Azaindoles and azaindolines are important core structures in pharmaceuticals and natural products, which have found wide applications in the field of medicinal chemistry. In this study, we developed a novel one-pot method for selectively synthesizing 7-azaindoles and 7-azaindolines, which can be generated by reactions between the readily available 2-fluoro-3-methylpyridine and arylaldehydes. The chemoselectivity is counterion dependent, with LiN(SiMe3)2 generating 7-azaindolines and KN(SiMe3)2 furnishing 7-azaindoles. A range of substituents can be introduced under these conditions, providing handles for further elaboration and functionalization.

Graphical abstract: Alkali-amide controlled selective synthesis of 7-azaindole and 7-azaindoline through domino reactions of 2-fluoro-3-methylpyridine and aldehydes
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