Iridium catalyzed cyclodimerization of imines to substituted piperazines

Resumen del póster presentado al Organometallic Chemistry Directed Towards Organic Synthesis (OMCOS) IUPAC International Symposium, celebrado en Sitges-Barcelona (España) del 28 de junio al 2 de julio de 2015.Piperazine is the basic skeleton of a broad class of organic compounds, which display a wide variety of biological activities. This pharmacophore is found in about 6% of all orally administered drugs due to its antitumor, antiviral, antifungal, and antibacterial properties. The synthesis of piperazines is usually achieved by reduction of (di)oxopiperazines, α-lithiation of Boc-protected piperazines, or by different cyclization reactions such as dialkylation of amines with bis(2-chloroethyl)amine, reductive cyclization of diimines, alkene carboamination, and the Mitsunobu reaction. However, the efficient synthesis of substituted piperazines often requires lengthy sequential synthesis, making the developments of diverse and efficient synthetic approaches highly desirable. In 2012, the groups of Li and Wolczanski reported the stoichiometric synthesis of substituted piperazines from deprotonated imines through the formation of binuclear titanium complexes. Although some valuable intermediates could be isolated, all the attempts to carry out the reactions in a catalytic manner were unsuccessful. In this communication we report a good catalytic method yielding fully substituted piperazines (2,3,5,6-tetraRpiperazines) mediated by the iridium complex [Ir(cod)Cl(PPh3)], and the characterization of related complexes. The formation of the desired heterocycle is produced by the cyclodimerization of the imine in a C-C diastereoselective coupling process. The scheme shows the proposed catalytic cycle for the bis(picolyl)imine (bpi) cyclodimerization.Peer Reviewe