Pd-catalyzed Suzuki-type cross-coupling of 2-pyridyl carbamoyl fluorides.

We describe a palladium-catalyzed Suzuki-type cross-coupling reaction of 2-pyridyl carbamoyl fluorides with boronic acids, which provides entry to medicinally relevant pyridyl amides. Mechanistic studies, including the synthesis and reactivity of carbamoyl Pd-F complexes, reveal the importance of both the fluoride electrophile and nitrogen directing group for aiding reactivity.

Fluoride-Catalyzed Cross-Coupling of Carbamoyl Fluorides and Alkynylsilanes.

We report the synthesis of alkynamides via the cross-coupling of carbamoyl fluorides and alkynylsilanes catalyzed by tetrabutylammonium fluoride (TBAF). In contrast to previously reported transformations of carbamoyl fluorides, C-F bond cleavage is achieved under exceptionally mild conditions (room temperature, low catalyst loadings, and short reaction times) without the need for strongly nucleophilic reagents and/or catalysts. This method offers distinct advantages over transition-metal-catalyzed approaches, such as tolerance to aryl halide moieties and complementary chemoselectivity.

Synthesis of Carbamoyl Fluorides Using a Difluorophosgene Surrogate Derived from Difluorocarbene and Pyridine -Oxides.

We report a method for the synthesis of carbamoyl fluorides from secondary amines using bench-stable, inexpensive, and readily accessible starting materials that, when combined, yield a surrogate for toxic difluorophosgene (COF) gas. In contrast to state-of-the-art methods for the synthesis of carbamoyl fluorides, our protocol does not require the use of pre-functionalized substrates, the preparation of light-, temperature-, and/or moisture-sensitive chemicals, or the application of explosive fluorinating reagents.