Modular synthesis of cyclic ß-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 ß-fluoroalkyl amines using a photoredox-catalysed cyclisation/hydrogen atom transfer reaction of bromodifluoroethylamines.

Borylated cyclobutanes via thermal [2 + 2]-cycloaddition.

A one-step approach to borylated cyclobutanes from amides of carboxylic acids and vinyl boronates is elaborated. The reaction proceeds via the thermal [2 + 2]-cycloaddition of in situ-generated keteniminium salts.

Spiro[3.3]heptane as a Saturated Benzene Bioisostere.

The spiro[3.3]heptane core, with the non-coplanar exit vectors, was shown to be a saturated benzene bioisostere. This scaffold was incorporated into the anticancer drug sonidegib (instead of the meta-benzene), the anticancer drug vorinostat (instead of the phenyl ring), and the anesthetic drug benzocaine (instead of the para-benzene). The patent-free saturated analogs obtained showed a high potency in the corresponding biological assays.