Biocatalytic C-H oxidation meets radical cross-coupling: Simplifying complex piperidine synthesis

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Biocatalysis

Background:

• Modern drug discovery increasingly requires complex molecules with high sp³ character (Fsp³) for enhanced specificity and properties.
• Synthesizing three-dimensional (3D) saturated molecules remains challenging due to limited derivatization strategies compared to flat sp² molecules.

Purpose of the Study:

• To develop a generalizable strategy for the rapid, modular, enantiospecific, and diastereoselective functionalization of piperidine.
• To provide a method analogous to established techniques for flat molecules, streamlining the synthesis of complex 3D structures.

Main Methods:

• The study combines robust biocatalytic carbon-hydrogen oxidation with radical cross-coupling.
• This approach enables the functionalization of piperidine, a saturated analog of pyridine.

Main Results:

• A novel, modular strategy for derivatizing 3D saturated molecules was successfully developed.
• The method allows for enantiospecific and diastereoselective functionalization, streamlining complex molecule synthesis.

Conclusions:

• This work presents a generalizable strategy for accessing complex molecular architectures with high sp³ character.
• The combined biocatalysis and radical cross-coupling approach offers significant advantages for medicinal and process chemists in drug development.