One-Pot Synthetic Approach to Dipyrromethanes and Bis(indolyl)methanes via Nitrosoalkene Chemistry

A one-pot regio- and stereoselective synthesis of a dipyrromethane and a bis(indolyl)methane based on two consecutive reactions of nitrosoalkenes with pyrrole or indole, respectively, is described as an experiment to be carried out by upper-division undergraduate students in a laboratory classroom. Importantly, the ability of electrophilic conjugated nitrosoalkenes to react via Michael addition or hetero-Diels–Alder reactions with electron-rich heterocycles will provide an opportunity for students to acknowledge alternative reaction pathways underlying certain transformations. Reactions were performed under mild conditions using water as a solvent, followed by purification through column chromatography on silica gel, and characterization of the desired products by NMR and IR spectroscopy. This laboratory experiment combines organic synthesis, determination of the purity of compounds (TLC analysis and melting point measurements), as well as structural analysis (interpretation of 1D NMR spectra). Several important organic chemistry concepts, such as stereo- and regioselectivity, in situ generation and reactivity of conjugated nitrosoalkenes, conjugated 1,4-addition reactions, and cycloaddition reactions, are also discussed.