Programmable Piperazine Synthesis via Organic Photoredox Catalysis.

Abstract

Piperazine cores have long been identified as privileged scaffolds in the development of pharmaceutical compounds. Despite this, the facile synthesis of diverse C-substituted piperazines remains a challenge without prefunctionalized substrates/cores. Herein, we describe a programmable approach to highly diversifiable piperazine cores, which circumvents the typical need for radical precursors. The use of organic photoredox catalysis renders this method operationally simple, as direct substrate oxidation followed by 6-endo-trig radical cyclization with in situ generated imines may furnish the product. Additionally, the photoredox-catalyzed anti-Markovnikov hydroamination of readily accessible ene-carbamates provides a modular approach to functionalized diamine starting materials which are shown to generate more complex piperazine cores. A wide range of both carbonyl and amine condensation partners were shown to be compatible with this system in good to excellent yield.