Photocatalytic Multicomponent Alkene Difunctionalization Strategies to Enhance molecular Complexity in Batch and Flow

This Thesis describes photocatalytic strategies for the valorization of feedstock chemicals to value added complex molecules in both batch and continuous flow. Special emphasis is placed on the development of three-component alkene difunctionalization methodologies that exploit the native functionalities of inexpensive and abundant commodity chemicals under mild reaction conditions. Chapter 1 provides a general introduction to the opportunities that multicomponent reactions (MCRs) have unlocked in modern synthetic chemistry, as well as to the mechanistic scenarios governing photocatalysis in both batch and flow. Chapter 2 reports a redox-neutral photoredox catalyzed Ritter-type carboamidation of aromatic olefins. The transformation harnesses non stabilized, nucleophilic primary radicals generated from readily accessible carboxylic acid-derived redox-active esters (RAEs) and merges the concept of radical polar crossover (RPC) with classical Ritter-type amidation chemistry. A simple modification of the alkene acceptor from aryl olefins to 1,1-diarylolefins redirects the reaction pathway towards the selective formation of Heck-type products, providing a chemodivergent platform. The method exhibits broad substrate scope, and continuous flow technology enables efficient scale up (up to multi-mmol scale) with just 100 minutes of residence time. Chapter 3 presents a photocatalyzed multicomponent oxo-amidomethylation of aromatic olefins under aerobic conditions, enabling the synthesis of N-(γ-oxopropyl)amides. The method relies on photocatalytic hydrogen atom transfer to selectively engage α-N-alkyl C(sp3)–H bonds in unactivated amides. Subsequent Giese-type radical addition to olefins and interception of the resulting carbon-centered radical by green and atom-economical molecular oxygen affords oxo functionalized homologated products. This cascade protocol demonstrates compatibility with a broad range of aryl olefins and amides and efficient scalability (up to 5 mmol scale). The synthetic utility of the resulting scaffolds is showcased through their downstream derivatizations.

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