Stereoselective synthesis of Nitrogen-containing bicycles from sodium benzoate

Nitrogenated bicycles are a highly repetitive motive in natural products such as alkaloids, and show a broad variety of biological activities. Our group pursues their preparation using as starting materials cis-ciclohexadienediols obtained via biotransformation of arenes using bacterial dioxygenases. Particularly, diol 1 can be obtained through enzymatic dihydroxylation of sodium benzoate by the enzymatic complex Benzoate Dioxygenase present in the mutant strain Ralstonia eutropha B9.
To avoid the regioselectivity problems observed when functionalizing the unsubstituted diene present in 1, our group has developed an intramolecular cyclization strategy for the preparation of nitrogen-containing bicycles. This strategy involves introducing a nitrogenated function on the carbonyl moiety, which can react as a nucleophile in halogen-promoted intramolecular cyclization. In this manner, we were able to obtain the beta-lactam 3, which with catalytic amounts of KCN gives aziridine 4. Different synthetic approaches for obtaining other nitrogenated bicycles will be presented.(1,2)