Malononitrile is a readily available feedstock chemical distinguished by its high acidity and unusual electronic structure. Guided by a “Freedom of Choice” philosophy in reaction discovery, we are exploring this underutilized reagent as a platform for inventing new, often enantioselective, transformations with the potential to simplify access to sp3-rich drug-like molecules. This lecture will highlight historical milestones in malononitrile…

Precision bioconjugation techniques are essential for constructing well-defined protein-based therapeutics such as antibody-drug conjugates (ADCs). Among native amino acids, cysteine is particularly attractive for site-selective modification due to its high nucleophilicity and low natural abundance. However, most proteins contain multiple free cysteines, making it challenging to target specific residues without affecting protein structure or…