Synthesis of Acyclic Nucleoside Analogues through the Insertion of Carbenoids into N−H Bond of Nucleobases

Abstract

AbstractA new and efficient approach for the synthesis of acyclic nucleoside analogues with different side chains has been established for the first time via the insertion of carbenoids into N−H bond of nucleobases. With Sc(OTf)3 as the catalyst, various purine bases and α‐diazoesters worked well, and gave the corresponding acyclic nucleosides in moderate‐to‐good yields (21 examples, up to 87 % yield) with good N9‐regioselectivities (up to >99:1). Moreover, other N‐heterocycles including pyrimidines, benzoimidazole, imidazole, carbazole, and pyrazole are also suitable substrates and afford the desired N−H insertion products with moderate‐to‐good yields. In addition, the enantioselective and chiral auxiliary induction N−H insertion reactions were also studied.