One-Pot Route from Halogenated Amides to Piperidines and Pyrrolidines

Abstract

Piperidine and pyrrolidine derivatives are important nitrogen heterocyclic structures with a wide range of biological activities. However, reported methods for their construction often face problems of requiring the use of expensive metal catalysts, highly toxic reaction reagents or hazardous reaction conditions. Herein, an efficient route from halogenated amides to piperidines and pyrrolidines was disclosed. In this method, amide activation, reduction of nitrile ions, and intramolecular nucleophilic substitution were integrated in a one-pot reaction. The reaction conditions were mild and no metal catalysts were used. The synthesis of a variety of N-substituted and some C-substituted piperidines and pyrrolidines became convenient, and good yields were obtained.

Direct synthesis of carbamates, thiocarbamates, and ureas from Boc-protected amines: a sustainable and efficient approach

“…28 In 2019, Baomin Fan's group achieved the direct conversion of Boc-protected amines with formates or alcohols to carbamates, catalyzed by Co and Zn. 29 As part of our program to develop efficient methods for synthesizing pharmaceutical products, [30][31][32][33][34] here we introduce a cost-effective and environmentally benign methodology for the direct synthesis of carbamates and their analogs from Boc-protected amines. This novel strategy employs tert-butoxide lithium (t-BuOLi) as the sole base, obviating the need for metal catalysts and eliminating the use of hazardous substances (Scheme 1).…”