New Carbon Reactivity Rules with Radical Carbenoids and Carbyne Equivalents Enabled by Photoredox Catalysis

Ana García Herráiz

García Suero, Marcos

The main objective of this Thesis was the discovery of conceptually new reactive carbon species, for the development of new rules of carbon reactivity and disconnections, which had not been previously appreciated in chemical synthesis. First, we developed a general platform for the generation of radical carbenoid species with a leaving group substituted radical species with photoredox catalysis. These reactive species allowed to develop a stereoconvergent cyclopropanation of styrenes with gem-diiodoalkane reagents and E/Z mixtures of olefins. Our new cyclopropanation reaction overcomes the limitations of current methods with respect to functional group tolerance, safety and ability to functionalize derivatives of biomolecules. Second, we have pioneered the generation of neutral carbyne equivalents with photoredox catalysis. This study revealed the unexplored dual cerbene/radical behavior and the ability of neutral carbynes to form three new bonds; and established the foundations for assembly-point functionalization for the sequencing of chiral centers, through diazo compounds, with simple arenes and medicinally important agents.

The new reagents developed during my doctoral thesis offer a new advancement in basic science that could have a transformative impact in the pharmaceutical and agrochemical industry by providing conceptually new synthesis of cyclopropane cores, and with the assembly-point construction of chiral centers for library development or for modification of bioactive candidates.

Conceptually New Reactive Carbon Species; Carbon Reactivity Rules; Disconnections; Chemical Synthesis; General Platform; Radical Carbenoid Species; Leaving Group Substituted Radical Species; Photoredox Catalysis; Stereoconvergent Cyclopropanation; Styrenes; Gem-Diiodoalkane Reagents; E/Z Mixtures of Olefins; Cyclopropanation Reaction; Functional Group Tolerance; Safety; Biomolecule Derivatives; Neutral Carbyne Equivalents; Dual Cerbene/Radical Behavior; Three New Bonds; Assembly-Point Functionalization; Sequencing of Chiral Centers; Diazo Compounds; Simple Arenes; Medicinally Important Agents