The coupling of aryl, heteroaryl, and vinyl halides with ,-difluoroketones or silyl ethers or siylenol ethers of ,-difluoroketones and ,-difluoroamides and esters are described. Further derivatization of the coupling products (such as ketone cleavage and Baeyer-Villiger oxidation) is also described.

The invention relates to compounds of use as targeted cytotoxic agents and methods of use thereof. In particular, the invention relates to prodrugs that are substantially resistant to human AKR1C3 enzyme metabolism, methods of cell ablation using said compounds and methods of treatment of cancer and other hyperproliferative disorders using said compounds.

Methods and systems and compounds and agents for the induction or modulation of ferroptosis in a cell, a tissue, or a tumor in a subject are provided. Various agents and compounds are described. Various methods of administration are described for optimal ferroptosis modulation, for instance, induction and killing of target cells. Methods of making, purifying, and characterizing various compounds are described.