Diethyl zinc mediated metalloamination : development and its application to the synthesis of functionalized pyrrolidines and piperidines

Abstract

The ability to synthesize nitrogen heterocycles of industrial and academic significance remains a central goal of organic synthesis. Substantial effort has been made to develop new methodologies that allow the construction of these targets in an atom economical and efficient manner. Herein, we describe the development of a metalloamination transformation mediated by diethyl zinc. The resulting organozinc intermediates undergo facile electrophilic addition, resulting in a one-pot reaction sequence to access functionalized pyrrolidines and piperidines. Optimization of the reaction conditions for the initial metalloamination/cyclization, as well as the addition of electrophiles was examined. The scope of the metalloamination, including functional group tolerance was evaluated by synthesizing a number of mono- and disubstituted hydrazinoalkenes. This new methodology provides the synthetic community with a variety of new tools for accessing academic and industrial molecules of interest.