Copper-Catalyzed Intramolecular Dehydrogenative Aminooxygenation: Direct Access to Formyl-Substituted Aromatic N-Heterocycles

摘要

Aminooxygenation of alkenes, a process in which nitrogen and oxygen atoms are added simultaneously across a carbon-carbon double bond, represents one of the most straightforward approaches to prepare vicinal amino alcohol derivatives, which are an important functional motif in many biologically active compounds. The regioselective intramolecular version of this process leads to a variety of nitrogen-containing heterocycles, in which an exocyclic oxygenated methylene group is present for further elaboration. In studies focusing on the development of this method, less-toxic metal catalysts, including palladium, copper, and iron, in addition to the toxic osmium salts have been explored. To elaborate the N-heterocycles formed in this fashion, deprotection (R'≠H) and oxidation strategies have been probed. In these efforts, oxidation of the exocyclic primary alcohols to form aldehydes, among the most versatile functional groups in chemical transformations, was found to be a general strategy. Herein, we describe the results of an investigation that has led to the discovery of an unexpected and novel intramolecular dehydrogenative aminooxygenation (IDA) reaction, catalyzed by copper and occurring under dioxygen. The process results in the direct formation of aromatic N-heterocycles substituted with a formyl group (Scheme 1).