The third generation of photoactivatable beads designed to capture bioactive small molecules in a chemo- and site-nonselective manner upon irradiation at 365 nm of UV light and release them as coumarin conjugates after exposure to UV light of 302 nm is described. These photoactivatable and photocleavable beads enable quantification of the amount and distribution of immobilized small molecules prior to the pull-down experiments to identify target protein(s) for the immobilized small molecules. The newly developed system was then used to analyze the functional group compatibility of the photo-cross-linking technology as well as the preferable nature of small molecules to be immobilized. As a result, compounds having a hydroxyl group, carboxylic acid, or aromatic ring were shown to give multiple conjugates, indicating that these compounds are well compatible with the photoactivatable beads system.

Despite the potential of α‐fluoroethers in medicinal chemistry, their synthetic methods, especially etherification of aliphatic alcohols, have been limited. Herein, we developed two‐ and three‐step gem‐difluoropropargylation of aliphatic alcohols including amino acid derivatives and naturally occurring bioactive molecules. Highly chemoselective etherification proceeded by using the gem‐difluoropropargyl bromide dicobalt complex in the presence of silver triflate and triethylamine. Decomplexation of dicobalt complexes was achieved by using cerium ammonium nitrate or N,N,N′‐trimethylethylenediamine. The thus obtained gem‐difluoropropargyl ethers were converted to various α‐difluoroethers which are expected to be useful for medicinal chemistry.

A benchtop-stable reagent for the catalytic Nicholas reaction with aromatic molecules was developed.

With the increasing importance of fluorine to medicinal chemistry and other areas, methods to access various fluorinated compounds are needed. Herein, we report the synthesis of difluoropropargyl vinyl ethers from ketones and aldehydes using difluoropropargyl bromide dicobalt complexes. We applied difluoropropargyl vinyl ethers to the synthesis of difluorodienone or difluoroallene under thermal conditions and trifluoro-pyran under acid-catalyzed conditions.