Strategies in Photocatalysis for the Synthesis of Non-Canonical Amino Acids
Time: Thu 2025-12-11 10.00
Location: F3, Lindstedtvägen 26
Language: English
Subject area: Chemistry
Doctoral student: Gregory R. Alvey , Organisk kemi
Opponent: Professor David J. Procter, University of Manchester, United Kingdom
Supervisor: Associate professor Markus D. Kärkäs, Organisk kemi; Professor Peter Dinér, Organisk kemi; Associate Professor Helena Lundberg, Organisk kemi; Assistant Professor Fredrik Schaufelberger, Organisk kemi
QC 2025-11-17
Embargo t.o.m. 2026-12-11 godkänt av skolchef Amelie Eriksson Karlström via e-post 2025-11-16.
Abstract
Visible-light photocatalysis has revolutionised synthetic chemistry by enabling the generation of reactive radical intermediates under mild conditions. Yet, the application of this strategy to the stereoselective synthesis of α-non-canonical amino acids (α-ncAAs) remains underdeveloped. This thesis explores photocatalysis as a general platform for constructing stereoenriched α-ncAAs by leveraging radical precursors derived from feedstock chemicals, radical activation modes, and coupling strategies.
Four complementary methodologies were developed to access α-amino acid derivatives from distinct starting materials. Deoxygenative C–O bond activation of oxalates derived from alcohols provides entry to alkyl radicals, while α-amino C–H functionalisation using both acridinium-based single-electron transfer and decatungstate-mediated hydrogen atom transfer delivered α-amino radicals and implemented these species into a C–C bond-forming transformation. A redox-neutral pathway was established for thioether activation, generating α-thioalkyl radicals directly from sulfides, and energy transfer catalysis was applied to oxime esters to forge quaternary α,α-disubstituted amino acids via radical–radical coupling.
Mechanistic studies, including quenching experiments, cyclic voltammetry, and computational investigations, elucidated the modes of radical generation and capture across these systems. Collectively, these findings demonstrate that the mechanisms accessible via visible-light photocatalysis, such as single-electron, proton-coupled electron transfer, and energy transfer, can be used as strategies for the synthesis of amino acids. The resulting methodologies not only expand the synthetic repertoire of radical chemistry but also establish new mechanistic paradigms for the stereocontrolled formation of α-ncAAs under photochemical conditions.