FULL PAPER DOI: 10.1002/ejoc.201402944 Reactivity of Dipyrromethanes towards Azoalkenes: Synthesis of Functionalized Dipyrromethanes, Calix[4]pyrroles, and Bilanes Susana M. M. Lopes, [a] Américo Lemos, [b] and Teresa M. V. D. Pinho e Melo* [a] Keywords: Synthetic methods / Cycloaddition / Nitrogen heterocycles / Azo compounds / Macrocycles The introduction of side chains at the 1- and 9-positions of dipyrromethanes was explored by using the hetero-Diels– Alder reaction of azoalkenes. New 5,5'-diethyldipyrro- methanes and 5-phenyldipyrromethanes that were function- alized with open-chain hydrazone moieties, including deriv- Introduction The research of dipyrromethanes has mainly been carried out by groups that are focused on porphyrin chemistry, as dipyrromethanes are particularly important building blocks in the preparation of porphyrins and porphyrin analogues, such as meso-substituted corroles, chlorins, expanded por- phyrins, and calix[4]pyrroles. [1] More recently, there has been a growing interest in the various other applications of dipyrromethanes, and this has led to a search for efficient strategies to functionalize dipyrromethanes, such as the syn- thesis of its 1,9-disubstituted derivatives. Dipyrromethanes are precursors to 4,4-difluoro-4-bora-3a,4a-diaza-s-ind- acene (BODIPY) dyes, the photophysical properties of which make them ideal fluorescent scaffolds for the devel- opment of high performance imaging probes. [2] Function- alized dipyrromethanes can function as photonic organic based materials, are potentially attractive structures in the development of new optical anion sensors, and have appli- cations in biological systems and the resolution of environ- mental problems. [1,3] In addition, calix[4]pyrroles can act as anion sensors. [4] These macrocycles are interesting struc- tures and can be used as anion molecular carriers to allow anions to cross lipid bilayer membranes, a topic that is par- ticularly relevant with regard to channelopathies. [4b] The 1,9-functionalization of dipyrromethanes can be achieved by exploring the rich electron density of the pyr- role units. Thus, these heterocyclic compounds can undergo acylation reactions, Vilsmeier reactions, Mannich reactions, and addition reactions to electron-poor heterocycles. [1a,1b] The dicyanation of 5-monosubstituted and 5-unsubstituted [a] Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal [b] CIQA, FCT, University of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal E-mail: tmelo@ci.uc.pt Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/ejoc.201402944. Eur. J. Org. Chem. 2014, 7039–7048 © 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 7039 atives with tetrazolyl groups, were prepared. Furthermore, the synthesis of new calix[4]pyrroles and bilanes was achieved by employing the bis(hetero-Diels–Alder) reaction of azoalkenes with 5,5'-diethyldipyrromethane. dipyrromethanes with chlorosulfuryl isocyanate has been reported. [5] In addition, 5,5-dialkyldipyrromethanes can un- dergo a reaction with phenyl isocyanate to afford mono- amide derivatives, and 1,9-bis(diazo)dipyrromethanes can be obtained by a reaction with diazonium salts. [6] Pyrrole can undergo a reaction with conjugated nitrosoalkenes and azoalkenes to give open-chain oximes and hydrazones, respectively. The formation of these products can be ex- plained by the rearomatization of the primarily formed cycloadduct, the bicyclic 1,2-oxazine or pyridazine (see Scheme 1). [7] Scheme 1. Functionalization of pyrrole through hetero-Diels–Alder reactions (DCM = dichloromethane). [7] This chemistry was explored as a new strategy for the functionalization of dipyrromethanes (see Scheme 2). [8] In a preliminary communication, we reported that 5,5'-diethyl- and 5-phenyldipyrromethanes participate in hetero-Diels– Alder reactions with nitrosoalkenes and azoalkenes to give dipyrromethanes with side chains that contain oxime and hydrazone groups, respectively. By controlling the stoichio- metry of the reaction, it is possible to obtain monosubsti- tuted or 1,9-disubstituted derivatives. More recently, we de- scribed a new one-pot approach to 5-substituted dipyrro-