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Enantioenriched azaarylmethyl amine derivatives are useful building blocks in synthetic and medicinal chemistry. To access these valuable motifs, an enantioselective palladium-catalyzed benzylation of azaarylmethyl amine pronucleophiles is introduced. Of note, this is a rare application of asymmetric (2-naphthyl)methylation of pro-nucleophiles with high p K a values (p K a ≈ 34 in DMSO). Control experiments support the notion that the coordination of Li + to the azaaryl nitrogen plays a critical role in the substitution process. With this procedure, enantioenriched (2-naphthyl)methylene azaarylmethyl amines with a variety of azaaryl groups (pyridyl, pyrazine, quinoxaline and isoquinoline) and cyclic and acyclic amines are readily obtained with good yields and enantioselectivities up to 99%.more » « less
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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(SiMe 3 ) 2 generating 7-azaindolines and KN(SiMe 3 ) 2 furnishing 7-azaindoles. A range of substituents can be introduced under these conditions, providing handles for further elaboration and functionalization.more » « less