Substituting Gaseous Reagents for Solid Alternatives

The aim of this project is to incorporate small alkyl chains into more complex organic molecules using easy to handle reagents. The type of reagents preferred in organic synthesis is solid, non-toxic, non- corrosive, and stable for a prolonged period of time without special precautions. Unfortunately, the reagents currently in use for the introduction of short alkyl chains do not fulfill these criteria in many cases, since they are often gaseous, toxic, or corrosive or even a combination of the aforementioned undesirable properties. So, what to do, in case you want to use such reagents, but change their properties to make handling easier? The hypothesis is that new reagents can be developed, which are solid and easy to handle themselves, but deliver in-situ the actual alkylation reagent, overall without experiencing the aforementioned unfavorable properties. For that purpose, we will look into several reagent classes, which can decompose under certain reaction conditions into reactive intermediates, which in turn can act as alkylating agents. Additionally, it has to be secured that the conditions required for liberating the alkylation reagent in-situ, are compatible with the other substrates, catalysts, and overall reaction conditions. The method development will start with selected test substrates and transformations, before the general scope of a certain method will be explored. Realizing this project will expand the scope of transformations which can be carried out under normal laboratory conditions without the need for special equipment (e.g. high-pressure reactors often required when working with gaseous reagents). Additionally, transformations with gaseous reagents are often actively avoided in university settings, where the reaction scale is typically in the mg region, and dosing gases in such small amounts is extremely difficult. Hence, this project will potentially open a new chemical space to be exploited in the future by chemists at all different types of institutions. Finally, the utility of the developed methods shall be demonstrated by the late- stage modification of known drug molecules.