Executive Summary : | Transition metal-catalyzed coupling reaction is one of the powerful strategies for the synthesis of various drug molecules under step-economy and rapidly generates the molecular complexity. However, the transition metal-catalyzed 1,2-difunctionalization of olefin is challenging due to other competing reactions such as the Heck reactions, cyclization, C-H functionalization through activation, and reductive Heck product in the presence of hydride donors. In this proposed research plan, we aim to develop earth-abundant metal-catalyzed enabled using carbon dioxide as a transient directing group to allow allylamines to undergo a site-selective difunctionalization. In the presence of carbon dioxide, the (alkenyl) amine is expected to form a carbamate and act as a transient directing group. The advantage of using CO2 is that the resulting carbamate is less sensitive to oxidation or substitution reactions, and the ability to use excess CO2 allows both substrate and product to be cheaply and easily protected during the reaction as the more chemically robust carbamate. Thus, our envision is that the formation of carbamic acids can direct a transition-metal for site-selective insertion to alkenes and prevent deleterious side reactions. Thus, using first-row transition metal catalysts the regioselective difunctionalization of secondary amine will be achieved. The difunctionalization of secondary amines is not known due to the difficulty to install directing group as well as remove it. These CO2 enabled site-selective difunctionalization (1,2- and 1,3-Difunctionalization of alkenyl amines, Synthesis of diverse N-heterocycles, and Enantioselective arylation of alkenyl amines) allow the straightforward synthesis of functionalized free amines under the step-, and atom-economic conditions. The free amine will be used directly for further transformation, including cascade reactions, allowing rapid access to new complex molecules. |