Photochemical In-Flow Synthesis of 2,4-Methanopyrrolidines: Pyrrolidine Analogues with Improved Water Solubility and Reduced Lipophilicity

A practical synthesis
of 2,4-methanopyrrolidines was elaborated.
The key synthetic step was an intramolecular photochemical [2 + 2]-cycloaddition
of an acrylic acid derivative in flow. In spite of a higher molecular
weight, 2,4-methanopyrrolidines were shown to have higher solubility
in water and lower lipophilicity than pyrrolidines, important characteristics
of bioactive molecules in drug design.