Combination of transition metal-catalyzed (hydro)formylation and organocatalysis for the tandem synthesis of diindolylmethanes, porphyrins and BODIPY fluorescent dyes

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Diindolylmethanes, porphyrins and BODIPYs are important classes of compounds with a large number of applications. However, the established synthesis of these compounds starting from aldehydes has several drawbacks: aldehydes are not always commercially available, so they often have to be prepared in an additional step. Many aldehydes are also extremely sensitive to oxidation and therefore difficult to handle. Furthermore, the use of acids such as TFA as catalysts can preclude sensitive substrates. Last but not least, undesirable side reactions such as polymerizations can also occur in the acidic reaction medium. This is a disadvantage especially in the synthesis of porphyrins which has to be compensated by high dilution in current methods.This research project will pursue a tandem reaction approach: via formylation reactions, such as rhodium-catalyzed hydroformylation or palladium-catalyzed formylation, the aldehydes will be generated directly in the reaction vessel from accessible and stable substrates such as alkenes or aryl halides. In the second reaction step, the in situ generated aldehydes react with aryl nucleophiles via Friedel-Crafts reaction. Organocatalysts, such as arylthioureas, are used to activate the carbonyl group of the aldehyde via hydrogen bonds. This could allow for much milder reaction conditions than the previous ones with acid catalysis. In addition to alkenes and aryl halides, allenes, alkynes and vinyl halides will also be used as substrates for the (hydro)formylation reactions. After optimization of the reaction conditions, an extensive library of diindolylmethanes will be synthesized using various indoles. Using pyrroles as aryl nucleophiles, dipyrromethanes will be generated as intermediates. If the second nucleophilic position in the pyrrole is blocked, BODIPY compounds are accessible by addition of an oxidizing agent, a base, and BF3•OEt2. However, if the second nucleophilic position is accessible, then porphyrinogens are built, which can be converted into porphyrins by oxidation. Therefore, various pyrroles with diverse alkenes, allenes, alkynes, as well as aryl and vinyl halides will be used to generate a wide range of BODIPYs and porphyrins. Furthermore, it is planned to apply the previously described methods for the synthesis of more complex products. An example with great application potential is the synthesis of chiral BODIPY compounds starting from styrenes. Here, the stereocenter has to be built up via enantioselective hydroformylation. Finally, the produced diindolylmethanes will be investigated for biological activity while the porphyrins and BODIPYs will be tested for optical properties.