Alkali-amide controlled selective synthesis of7-azaindole and 7-azaindoline through domino reactions of 2-fluoro-3-methylpyridine andaldehydes

Xinyu Xu,a Mingjie Ou,a Yan-En Wang,b Tingzhi Lin,a Dan Xiong,a Fei Xue, c

Patrick J. Walsh d and Jianyou Mao *a

aTechnical Institute of Fluorochemistry (TIF), Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, 30 South Puzhu

Road, Nanjing 211816, P.R. China

Abstract: Azaindoles and azaindolines are important core structures in pharmaceuticals and natural products, which have found wide applications in the field of medicinal chemistrty. 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 arylaldehyde. The chemoselectivity is counterion dependent, with LiN(SiMe₃)₂ generating 7-azaindolines  and KN(SiMe3)2 furnishing 7-azaindoles.  A range of substitutes can be introduced under these conditions, providing handles for further elaboration and functionalization.

Org. Chem. Front., 2022, 9, 2541–2548 (2021年影响因子: 5.456).

论文链接：https://pubs.rsc.org/en/content/articlelanding/2022/QO/D2QO00339B