Visible light-mediated alkyl radical additions to alkenyl and alkynyl silanes

Abstract

<p>Radicals are reactive species that possess a unique reactivity, which enables them to form unusual bonds unreachable by ionic chemistry. In the last twenty years, radical chemistry has benefited from a renewed interest due to the emergence of methods that can initiate radical reactions under mild conditions. Among those, visible light-mediated radical chemistry has become established as a powerful synthetic strategy and is to this day a fast-growing field. <p>Organosilanes are a highly useful and versatile class of compounds that have found multiple applications in synthetic chemistry. Despite belonging to the same periodic table group, significant differences exist between carbon and silicon, which impact their reactivities. While radical additions to unsaturated C-C bonds are well known, similar additions to alkenyl and alkynyl silanes remain underexplored. The work presented in this thesis aimed to investigate and develop new methods for the visible light-mediated intra- and intermolecular addition of alkyl radicals onto vinyl and alkynyl silanes. <p>First, we have developed a general protocol for the introduction of vinyl and alkynyl groups onto sp3 carbons from activated and unactivated alkyl iodide radical precursors, using vinyl and alkynyl silyl tethers as radical acceptors. Mechanistic investigations revealed that the intramolecular photoredox catalyzed radical group transfer of the vinyl or alkynyl group from silicon to carbon proceeds through a pathway involving both single electron transfer (SET), halogen atom transfer (XAT) and chain propagation, which also includes radical cyclization and spontaneous ring fragmentation of the resulting cyclic intermediate. The protocol was successfully applied to a wide range of substrates and afforded the desired products in moderate to excellent yields with high diastereoselectivities. <p>Second, we investigated the photoredox catalyzed intermolecular radical addition of electron-deficient radicals onto divinyltetramethyldisiloxane. To our surprise, the anticipated radical cyclization did not take place, but a product resulting from an atom transfer radical addition (ATRA) process was formed instead. Thus, we turned our attention to the optimization of the intermolecular ATRA reaction. While this work requires further investigation, it orientated us towards our third objective. <p>Finally, we developed a preliminary protocol for the photocatalyst-free visible light-mediated intermolecular ATRA reaction between α-iodoketones and trimethylvinylsilane. The protocol was successfully applied to a selection of substrates. However, a high variability of isolated yields was observed despite extensive screening of the reaction conditions, which suggests that the optimal conditions may be substrate dependent. We postulated that the desired ATRA reaction was initiated by photoexcitation of a halogen bond (XB) complex and operated through chain propagation. <p>Overall, we have successfully developed both inter- and intramolecular radical addition processes of alkyl radicals to vinylsilanes. Through our work, we have exploited multiple ways to generate alkyl radicals from alkyl halide precursors using visible light-mediated techniques, and have gained insight onto the different mechanisms of these reactions. We anticipate that these results will establish alkenyl and alkynyl silanes as radical acceptors in contemporary radical chemistry.