The Persistent Radical Effect in Organic Synthesis.

Abstract

Radical-radical couplings are mostly nearly diffusion controlled processes. Therefore, the selective cross-coupling of two different radicals is challenging and not a synthetically valuable process. However, if the radicals have a different lifetime and if they are generated at equal rates, cross-coupling will become the dominant process. This high cross-selectivity is based on a kinetic phenomenon called the persistent radical effect (PRE). In this review, an explanation of the PRE supported by simulations of simple model systems is provided. Radical stabilities are discussed within the context of their lifetimes and various examples of PRE-mediated radical-radical couplings in synthesis are discussed. It is shown that the PRE is not restricted to the coupling of a persistent with a transient radical. If one coupling partner is longer-lived than the other transient radical, the PRE operates and high cross-selectivity is achieved. This important point expands the scope of PRE-mediated radical chemistry. The review is divided in two parts. The 1st part is dealing with the coupling of persistent or longer-lived organic radicals. In the 2nd part, radical-metal crossover reactions , metal centered radical species and more generally longer-lived transition metal complexes able to react with radicals are discussed - a field that has flourished recently. The combination of radical σ-bond formation with transition-metal-mediated σ-bond construction significantly enlarges the radical chemistry space. Advantages of both areas are synergistically combined and C-C bond formations not accessible via traditional radical approaches become feasible. Moreover, the metal-mediated coupling step also allows for enantioselective bond formation. Although great progress has been achieved over the years in enantioselective radical chemistry, the radical-metal crossover approach offers advantages, in particular considering the non-existing background coupling leading to racemic compounds.