Application of Cope-type hydroamination in the synthesis of hydrazones and the total synthesis of the benzyltetrahydroisoquinoline norreticuline

Abstract

The hydroamination of alkenes and alkynes is a highly desirable, yet underdeveloped approach to nitrogen incorporation into molecules. Currently, this approach is predominantly limited to transition metal catalysis and suffers from limitations in substrate scope and functional group compatibility. The focus of thesis is the development of simple, metal-free hydroaminations through a different approach that is concerted in nature: the Cope-type hydroamination (eq. 1). This transformation was applied towards the intermolecular hydroamination of alkynes with hydrazines, and is regioselective for the linear, "anti-Markovnikov" isomer 5 (eq. 2) and is presented in Chapter 2. This methodology has also been applied to intramolecular cyclizations and has been extended towards the synthesis of natural products with a specific focus on the challenging formation of 6-membered rings. The total synthesis of the benzyltetrahydroisoquinoline alkaloid norreticuline 8 through a Cope-type hydroamination key step (eq. 3) is presented in Chapter 3.