1.11 Generation of Radicals from Organoboranes

Radicals can be generated by the cleavage of the C—B bond of alkylboranes or boronic acid derivatives. The fragmentation process may result from a nucleohomolytic substitution process or from a redox process. The nucleohomolytic substitution is ideal for the generation of alkyl radicals and is usually part of a chain-reaction process. Redox processes (mainly oxidative reactions) have been used to generate both alkyl and aryl radicals. The use of stoichiometric oxidizing agents can be avoided by employing photoredox catalysis. A broad range of synthetic applications such as radical cascade processes, multicomponent reactions, and cross-coupling reactions in the presence of suitable metal catalysts are now possible. In their diversity, organoboron compounds represent one of the most general sources of radicals. The merging of radical chemistry with the classical chemistry of organoboron derivatives opens tremendous opportunities for applications in organic synthesis.

1.9 Oxygen-Centered Radicals

Oxygen-centered radicals (R1O•) are reactive intermediates in organic synthesis, with versatile synthetic utilities in processes such as hydrogen-atom transfer (HAT), β-fragmentation, radical addition to unsaturated carbon–carbon bonds, and rearrangement reactions. In this review, we focus on recent advances in the generation and transformation of oxygen-centered radicals, including (alkyl-, α-oxo-, aryl-) carboxyl, alkoxyl, aminoxyl, phenoxyl, and vinyloxyl radicals, and compare the reactivity of oxygen-centered radicals under traditional reaction conditions with their reactivity under visible-light-induced reaction conditions.

1.10 Boron-Centered Radicals

Boryl radicals have emerged as powerful radical intermediates in organic synthesis. This review summarizes recently developed transformations involving boryl radical species, including C—B bond formation reactions, reduction reactions, and radical catalysis.

1.12 Intermolecular Radical C—H Functionalization

The generation of carbon-centered radicals via intermolecular hydrogen-atom transfer (HAT) from C—H bonds to an abstracting species (HAT reagent) represents a significant challenge in terms of reactivity, site-selectivity and stereoselectivity. The radical species resulting from such a transfer can then engage in carbon—carbon or carbon—heteroatom bond formation, possibly through the intervention of transition-metal catalysts, leading to a variety of functionalized products. This chapter aims to provide the reader with useful guidelines to understand, predict, and design selective radical transformations based upon initial HAT from a C—H bond coupled to different radical-capture strategies. A selection of examples that illustrate different approaches to implement HAT reactions in synthetically useful procedures are presented.

1.14 Palladium(I)-Mediated Reactions

Several elegant reactivities can be observed in reactions involving palladium(I) species, allowing access to molecular architectures that are often beyond the capabilities of popular diamagnetic palladium complexes. This review presents three main axes of research in this context, which have mostly emerged in the last decade. Reactions promoted by visible light enable synthetic methods that are unusual in their mild experimental conditions coupled with remarkably broad functional group tolerance. The use of discrete palladium(I) dimers as precatalysts allows one to perform a wide set of cross-coupling protocols, such as Kumada and Negishi reactions, and chalcogenation reactions, with a surgical precision on the carbon—halogen bond that is initially activated. The generation of alkyl radicals and palladium(I) species through a thermal strategy proves useful for the elaboration of substrates with several polyfluorinated fragments, which are otherwise elusive coupling partners for more common two-electron processes.

1.3 Modelling Radicals and Their Reactivities

In this chapter, the application of computational quantum mechanical methods to the understanding of radical reactions is introduced. For radical reactions, access to electronic configurations through quantum chemical calculations allows rationalization of unusual reactivities. Using the valence bond approach, the nature of bonding in three-electron bonds can be characterized by large resonance interactions. Similarly, some simple reactions that are commonly believed to be radical-free, such as [3 + 2] cycloadditions, are in fact governed by a high-lying biradical intermediate that helps to stabilize the transition state. More complex radical and enzymatic reactions can also be modelled, as illustrated by the example of horseradish peroxidase. These case studies show that computational analysis can complement experimental investigations and fill in the blanks to enable a more complete understanding of radical reactions.

1.13 Intramolecular Hydrogen-Atom Transfer

Recent advances in intramolecular hydrogen-atom transfer (HAT) have demonstrated significant utility in C—H functionalization through highly reactive open-shell intermediates. The intramolecular transposition of radical reactivity from select functional groups to generate more stable carbon-centered radicals often proceeds with high regioselectivity, providing novel bond disconnections at otherwise inert and largely indistinguishable positions. This chapter explores the functional groups capable of intramolecular HAT to generate remote radicals and the transformations currently available to the synthetic chemist.

1.5 Photochemistry and Radical Generation: Approaches in Mechanism Elucidation

The development of photocatalytic reactions has reemerged as an active area of research in organic synthesis. A large variety of synthetically valuable transformations have now been developed that take advantage of the ease by which photocatalysts generate a variety of open-shelled reactive intermediates. The study of the mechanisms of these reactions, however, is a challenge, especially in increasingly sophisticated reactions that often involve multiple steps and complex reaction mixtures. Multiple complementary techniques often need to be utilized in tandem in order to develop a detailed understanding of these reactions. The first part of this review outlines many of the most common techniques that are used to interrogate the initiation and product-formation steps of a photocatalytic transformation. The second part describes case studies that provide contextual examples of how photophysical, electrochemical, physical organic, and computational investigations can be used together to provide insights into the mechanisms of complex photocatalytic reactions.