Decarboxylative Functionalization of Amino Acids with Nickel-Photoredox Catalysis

A central objective of this thesis is to convert empirical Nickel-photoredox reactivity into a mechanistically predictive system. The work addresses photoredox reactivity through both SET and EnT manifolds, using photocatalyst properties to rationalize which regime operates in a given transformation. In parallel, the Nickel manifold is dissected using experimentally anchored DFT analysis to identify key organonickel intermediates, oxidation-state changes, and pathway bifurcations. This mechanistic understanding is then translated into method development for amino-acid-derived substrates, enabling selective access to non-natural amino acids and enamide. Chapter 2 investigates decarboxylative arylation of Boc-protected amino malonic acids, probing a glycyl-radical pathway; captodative effects are assessed by SOMO–LUMO and radical-polarity analysis. Chapter 3 evaluates substrates with reduced captodative character and identifies a divergence between arylation and elimination, highlighted by aspartate and supported by DFT as branching from a common Ni(III) intermediate. Chapter 4 systematizes the elimination pathway to furnish 28 enamides and defines Nickel mediated β-elimination and photochemical E/Z isomerization. Chapter 5 converts amino acrylates into cyclic amino acids via EnT-driven [2+2] photocycloaddition, implicating diradical intermediates. Chapter 6 extends the platform to mild oxidation of alcohols and amines, enabling ketone and imine synthesis and demonstrates applicability beyond amino acid functionalization in synthesis.