Modular synthesis of cyclic β-difluoroamines

Fluorine-containing saturated nitrogen heterocycles are very attractive structures in medicinal and biological chemistry because fluorine can be used to tune conformation as well as key properties such as basicity and bioavailability. At present cyclic fluorinated amines are accessed using hazardous reagents such as DAST or by lengthy synthesis routes. Here we report a modular two-step synthesis of cyclic β-fluoroalkyl amines using a photoredox-catalysed cyclisation/hydrogen atom transfer reaction of bromodifluoroethylamines.

Fluorinated organic molecules underpin a range of scientific fields and are used extensively in pharmaceutical and agrochemical research. For example, fluorination of amines lowers their basicity and can also modulate acute toxicity and lipophilicity. Given that saturated heterocyclic amines are very common in bioactive compounds, fluorine-containing analogues would be of significant value, particularly in the field of drug discovery.