Decarboxylative Fluoroalkylation and Fluorination Strategies for Modulating Properties of Neurotherapeutics

Alcohols, ketones and aldehydes represent some of the most commonly exploited functional groups for synthetic transformations, and the extensive number of these motifs in natural products and pharmaceutically important building blocks provides a wide variety of potential substrates for transformations. In this field, we have developed new reactions and synthetic sequences using decarboxylative strategies and fluorinated alkenes to convert simple O-based functional groups into biomedically significant fluorinated substructures, and confirmed that these methods streamline the syntheses of target molecules. These methods enable synthetic chemists to efficiently access new fluorinated target molecules with physicochemical and biophysical properties that align with drug-like characteristics. Additional ongoing work aims to employ fluorinated peptidomimetics and ethermimetics to perturb physicochemical and biophysical properties of neurotherapeutics.