Research in our group centers on the design of conceptually new synthetic methods and the creation of unique molecular structure. Different aspects of selectivity, reaction regulation and valorization of abundant resources inspire us to develop streamlined procedures applicable in both, discovery chemistry and process development. We are actively engaged in investigating novel approaches for catalyst-stereocontrolled transformations and the preparation and utilization of bifunctional organomagnesium reagents with a focus on arene-formation and the synthesis of heterocyclic compounds.
Stereoselective Arene-Forming Aldol Condensation
The selectivity of the aldol condensation in aromatic polyketide biosynthesis induced by a cyclase-controlled folding of poly-β-ketones sparked our interest to investigate stereoselective arene-forming aldol condensation reactions of corresponding aldehyde substrates by amine catalysis. By transferring the stereochemical information of the catalyst into configurationally stable atropisomers, a general strategy to prepare rotationally restricted compounds by de novo construction of an aromatic ring was realized.
This approach was successfully implemented for the atroposelective synthesis of atropisomeric biaryls, oligo-1,2-naphthylenes and aromatic amides: After a concise synthesis of the ketoaldehyde substrates, addition of chiral amine catalysts resulted in the formation of biaryls with excellent stereoselectivity. This reaction scheme was subsequently extended by a building block addition strategy to enable the synthesis of oligo-1,2-naphthylenes; configurationally stable representatives of otherwise stereodynamic helical ortho-phenylenes. The generality of the concept was confirmed by preparing atropisomeric aromatic amides with a restricted Ar–CO bond rotation. Addition of the catalyst to the substrates triggers a highly selective arene-formation within minutes at ambient temperature.
Direct Ester to Arene Transformation
Cross coupling reactions unquestionably belong to the most powerful and general methods in organic synthesis. Nevertheless, several drawbacks remain even after monumental efforts to refine these transformations. Substrates are generally prepared specifically for this purpose, reaction conditions are frequently harsh, traces of transition metals are difficult to remove to the required levels and discovery routes are often replaced during route scouting.
A comparably simple retrosynthesis was identified by replacing the exocyclic bond disconnection with a retro-[5+1]-ring construction. With this analogy, prefunctionalized substrates can be replaced by ubiquitous esters as the addition of 1,5-bifunctional organomagnesium reagents leads to cyclohexa-2,5-dienolates, which subsequently convert to arenes by a 1,4-elimination reaction.