General

 

Our research is dedicated to the chemistry of reactive small molecules and their application to organic synthesis.

Our key technologies:

  • reactive intermediates in organic synthesis
  • continuous-flow chemistry
  • medicinal chemistry
 

Diazoalkanes in Organic Synthesis

Iron catalyzed carbene transfer reactions Copyright: Rene Koenigs

Our research is dedicated to the chemistry of reactive small molecules and their application to organic synthesis. The challenges when working with diazoalkanes is toxicity and risk of explosions, which renders the utilization of special synthesis equipment necessary. In particular, safety during scale-up to multi-gram scale is of significant importance to development programs in pharmaceutical and agrochemical industry. Therefore, the development of safe and efficient methods for the preparation of diazomethane analgoues in continuous-flow is of great interest. In other research areas, we are involved in the development of sustainable, efficient carbene transfer reactions.

Iron catalyzed carbene transfer reactions

Diazoacetonitrile was first described by T. Curtius in 1898. The molecular formula is C2HN3. Not surprisingly, this small diazo compound is highly explosive and so far there are only a few reports of its use in organic synthesis. In our previous work, we reported on the safe representation of in situ and continuous-flow methods and were thus able to show that diazoacetonitrile can be used efficiently in a number of important transformations. In addition to studying highly reactive diazoalkanes, we are interested in catalytic reactions of diazoalkanes with inexpensive non-noble metal catalysts. Our focus here is on the development of new protocols for the generation of diazoalkanes as well as their implementation with iron catalysts.

 

Flow chemistry and fluorinated diazoalkanes

Diazo acetonitrile in cyclopropanation reactions Copyright: Rene Koenigs

Fluorinated diazoalkanes are an important class of compounds for the introduction of fluoroalkylated groups, such as the trifluoro or the difluoromethyl group. In this context, our group is concerned with the preparation of fluorinated diazoalkanes in continuous flow and their application in organic synthesis. This approach allows the safe handling of these reactive and valuable synthetic intermediates in order to realize new approaches for the presentation of pharmaceutically and agrochemically interesting molecules.

 

Photochemical, metal-free carbene transfer reactions

Synthesis of difluoromethyl cyclopropanes Copyright: Rene Koenigs

Carbene transfer reactions with diazoalkanes are nowadays commonly carried out with a variety of noble metal or non-noble metal catalysts. Although diazoalkanes are intensely colored, photolysis with visible light to release a carbene has been poorly studied. Based on our work on rhodium-catalyzed carbene transfer reactions, we were interested in whether the photolysis of donor-acceptor diazoalkanes with visible light allows access to free carbenes, which can subsequently be used in cyclopropenation or rearrangement reactions. In fact, we were able to perform these reactions with simple, commercially available blue LEDs and realize a wide variety of different cyclopropenation, rearrangement and X-H insertion reactions in this way.