Jérémy Merad

Photo‐induced hydrogen atom transfer (HAT) catalysis has become a powerful platform for the direct and selective functionalization of ubiquitous C─H bonds. Traditionally, the outcome of these transformations is dictated by the interplay between C─H bond dissociation energies and polar effects, enabling predictable yet inherently substrate‐controlled selectivity. Recently, a fundamentally new strategy has emerged that relies on the catalytic and reversible modulation of substrate electronics to transiently enhance the reactivity of targeted C─H bonds. Notably, catalytic full or partial deprotonation of oxygen‐ and nitrogen‐containing functional groups has proven remarkably effective in selectively activating adjacent C─H bonds toward HAT, a phenomenon known as the anionic substituent effect. Rather than relying solely on the intrinsic properties of a substrate, this concept allows chemists to reprogram C─H bond reactivity in situ, unlocking previously inaccessible levels of selectivity in the direct functionalization of abundant functional groups under mild photocatalytic conditions. In this minireview, we discuss the mechanistic principles underpinning catalytic anionic substituent effects (CASE), the diverse strategies developed to generate them, and their impact on photocatalytic HAT‐mediated C–H functionalization. By highlighting recent advances and emerging opportunities, we illustrate how transient electronic activation is reshaping the design of selective C–H functionalization reactions.

Photo‐induced hydrogen atom transfer (HAT) catalysis has become a powerful platform for the direct and selective functionalization of ubiquitous C─H bonds. Traditionally, the outcome of these transformations is dictated by the interplay between C─H bond dissociation energies and polar effects, enabling predictable yet inherently substrate‐controlled selectivity. Recently, a fundamentally new strategy has emerged that relies on the catalytic and reversible modulation of substrate electronics to transiently enhance the reactivity of targeted C─H bonds. Notably, catalytic full or partial deprotonation of oxygen‐ and nitrogen‐containing functional groups has proven remarkably effective in selectively activating adjacent C─H bonds toward HAT, a phenomenon known as the anionic substituent effect. Rather than relying solely on the intrinsic properties of a substrate, this concept allows chemists to reprogram C─H bond reactivity in situ, unlocking previously inaccessible levels of selectivity in the direct functionalization of abundant functional groups under mild photocatalytic conditions. In this minireview, we discuss the mechanistic principles underpinning catalytic anionic substituent effects (CASE), the diverse strategies developed to generate them, and their impact on photocatalytic HAT‐mediated C–H functionalization. By highlighting recent advances and emerging opportunities, we illustrate how transient electronic activation is reshaping the design of selective C–H functionalization reactions.

The (3 + 2) cycloaddition reaction is a widely utilized strategy in organic synthesis for constructing cyclopentane frameworks, a structural motif prevalent in many bioactive compounds and pharmaceutical applications.

Les 1,3-diols acycliques sont des motifs ubiquitaires, essentiels dans la structure de nombreux produits naturels. Le développement d’approches permettant leur obtention de manière énantiosélective se révèle donc d’un grand intérêt synthétique. Dans ce contexte, notre équipe a envisagé une stratégie reposant sur des transferts d’acyle énantiosélectifs organocatalysés multiples. Cette approche a abouti à la mise en oeuvre d’une méthodologie de désymétrisation énantiosélective organocatalysée de 1,3-diols méso acycliques. Les composés ainsi obtenus constituent des briques moléculaires aisément valorisables en synthèse totale. Une approche similaire a permis de décrire, dans un second temps, une méthode inédite de double dédoublement cinétique de 1,3-diols anti. Générale et pratique, ce procédé fournit des diols énantiopurs de structures variées. La particularité de ces méthodologies réside dans l’exploitation du principe de Horeau se traduisant par une amplification de l’énantiosélectivité déployée par le catalyseur chiral. Les isothiourées employés dans ces réactions constituent une famille de bases de Lewis azotées dont la capacité à promouvoir les réactions d’acylation énantiosélectives n’a été découverte que récemment. Bien que leur utilisation en catalyse énantiosélective se soit rapidement démocratisée, les éléments structuraux responsables de leur sélectivité n’ont pas été totalement identifiés. Avec le nouvel objectif d’établir une relation entre structure, réactivité et sélectivité de ces molécules, des isothiourées originales ont été synthétisées et leur potentiel catalytique étudié en détail.

Abundant C-H and C-C bonds can undergo homolytic cleavage through radical processes, enabling the subsequent formation of new C-C bonds that profoundly reshape molecular architectures. Yet, merging these distinct elementary steps into a single catalytic blueprint capable of achieving full skeletal reorganization has remained highly challenging due to the complex orchestration of the intricate sequence. Herein, we report a photoredox-catalyzed C-H alkylation intricately coupled to a round-trip radical cascade that delivers a striking skeletal remodeling of cyclopropyl alkanols. The use of a carbon dioxide atmosphere proves essential for ensuring the reaction efficiency and expanding the reaction scope. Mechanistic studies uncover that in situ generated catalytic salts play a decisive role in choreographing the radical cascade and enabling key steps of the transformation.

Chalcogenyl radicals are powerful catalysts for covalent radical catalysis (CoRC), enabling the design of efficient radical cascades that transform simple substrates into valuable molecular architectures. Among them, selenium-centered radicals exhibit particularly attractive reactivity profiles, yet their broader exploitation has been hampered by the limited availability of suitable precursors. Herein, we report a novel family of dicationic diselenides that act as readily activatable reservoirs of selenyl radicals. Their physicochemical properties are elucidated, and their catalytic competence in CoRC is demonstrated, establishing dicationic diselenides as a new platform for selenium-based radical catalysis.

Abundant C–H and C–C bonds can undergo homolytic cleavage through radical processes, enabling the subsequent formation of new C–C bonds that profoundly reshape molecular architectures. Yet, merging these distinct elementary steps into a single catalytic blueprint capable of achieving full skeletal reorganization has remained highly challenging due to the complex orchestration of the intricate sequence. Herein, we report a photoredox-catalyzed C–H alkylation intricately coupled to a round-trip radical cascade that delivers a striking skeletal remodeling of cyclopropyl alkanols. The use of a carbon dioxide atmosphere proves essential for ensuring the reaction efficiency and expanding the reaction scope. Mechanistic studies uncover that in situ generated catalytic salts play a decisive role in choreographing the radical cascade and enabling key steps of the transformation.

The recent development of photoredox and energy transfer catalysis has led to a significant expansion of visible‐light‐driven chemical transformations. These methods have demonstrated exceptional efficiency in converting a wide range of substrates into radical intermediates and generating open‐shell catalytic species. However, the simplification of catalytic systems and the direct generation of highly reactive radical organocatalysts through direct visible‐light irradiation from stable precatalysts remains largely an unrealized goal. This challenge is mainly due to the limited availability of precatalysts that are responsive to visible light. Herein, we introduce a new class of bench‐stable dicationic disulfuranes, which release highly reactive thiyl radicals upon blue‐light excitation. Spectroscopic and computational studies reveal that this reactivity arises from a combination of structural features and intermolecular interactions. This family of molecules has been employed to catalyze radical cascades previously incompatible with photoredox conditions, enabling the efficient formation of 1,2‐dioxolanes and 1,3‐hydroxyketones in excellent yields and short reaction times.

The recent development of photoredox and energy transfer catalysis has led to a significant expansion of visible‐light‐driven chemical transformations. These methods have demonstrated exceptional efficiency in converting a wide range of substrates into radical intermediates and generating open‐shell catalytic species. However, the simplification of catalytic systems and the direct generation of highly reactive radical organocatalysts through direct visible‐light irradiation from stable precatalysts remains largely an unrealized goal. This challenge is mainly due to the limited availability of precatalysts that are responsive to visible light. Herein, we introduce a new class of bench‐stable dicationic disulfuranes, which release highly reactive thiyl radicals upon blue‐light excitation. Spectroscopic and computational studies reveal that this reactivity arises from a combination of structural features and intermolecular interactions. This family of molecules has been employed to catalyze radical cascades previously incompatible with photoredox conditions, enabling the efficient formation of 1,2‐dioxolanes and 1,3‐hydroxyketones in excellent yields and short reaction times.

Two racemic anti-4,6-diphenyl-5,5-difluoro-1,3-dioxanes were prepared and the corresponding enantiomers were evaluated as potential new chiral dopants for liquid-crystal compositions.