Solving the challenging synthesis of highly cytotoxic silver complexes bearing sterically hindered NHC ligands with mechanochemistry.

The use of ball-mills enabled the straightforward synthesis of a variety of silver(i) complexes featuring challenging NHC ligands. Sterically hindered including electron-poor or with very low solubility imidazolium salts were ground with silver(i) oxide to furnish heteroleptic or homoleptic complexes in high yields and short reaction times. The synthesis of heteroleptic bis-NHC silver(i) complexes was also performed for the first time in a ball mill. The efficiency and rapidity of the mechanochemical approach enabled the generation of a library of unprecedented NHC silver complexes, whose cytotoxicity on the HCT116 colorectal cancer cell line was evaluated providing a rare example of medicinal mechanochemistry. The cationic silver complexes were found to be more potent than the neutral analogues, with IC50 values down to 21 nM and 256 times more potent than cisplatin.

Preparation of tetrasubstituted olefins using mono or double aerobic direct C-H functionalization strategies: importance of steric effects.

A novel protocol for the synthesis of tetrasubstituted olefins through a biomimetic approach has been explored. Both mono- and diarylations were performed under ambient oxygen pressure, giving a range of highly hindered tetrasubstituted alkenes. For diarylation of disubstituted substrates, it was demonstrated that the second arylation is the rate-limiting step of the overall transformation.