Carbon–Carbon Bond‐Forming Reactions Promoted by Trivalent Manganese

Abstract In the past decade, major advances in radical chemistry have been made by the use of transition metals. This field has witnessed impressive accomplishments, and tremendous potential lies ahead. There are many transition metal‐mediated methods for producing radicals, including (a) oxidation of CH bonds or unsaturated fragments by transition metals in higher oxidation states, (b) reduction of CX bonds or unsaturated moieties by transition metals in lower oxidation states, and (c) homolysis of metal–carbon σ bonds. Redox methods for generating radicals are well elaborated and utilize transition metals in different oxidation states. In the vast majority of these reactions, transient organometallic species have not been either isolated or identified. Their tentative structures have been proposed, in some cases based solely on chemical logic. Accordingly, the mechanisms of these multistep interactions have not been fully established. Particularly lacking is a clear recognition of those elementary steps that occur inside the ligand sphere of the transition metal. In comparison with traditional methods of radical generation, redox initiators demonstrate remarkable regioselectivity and are especially efficient in polyfunctional organic compounds. Furthermore, new types of radicals, inaccessible by traditional approaches, can be successfully generated. The main difference lies in the multiple roles that metal oxidants play during the reaction, namely, one‐electron transfer between proradical and transition metal to produce radical species, followed by redox interaction with intermediate adduct radicals. For this reason, metal‐mediated reactions differ significantly from those of peroxide‐ or light‐initiated processes. Trivalent manganese occupies a rather unusual place among metal oxidants in higher oxidation states and is particularly useful in this field. Numerous novel regio‐, chemo‐, and stereoselective synthetic methods have been developed in both inter‐ and intramolecular reactions, and their applicability to the construction of complex natural and biologically active compounds has been demonstrated. Despite its growing significance for synthetic chemistry, manganese(III)‐mediated reactions have not been comprehensively reviewed in recent years. The subject of this chapter is the radical carbon–carbon bond‐forming reaction induced by trivalent manganese derivatives such as Mn(OAc) 3 ,Mn(acac) 3 , and Mn(pic) 3 . It includes the oxidative generation of α‐ or α,α‐dioxoalkyl or alkyl radicals and their subsequent addition to unsaturated moieties. Both inter‐ and intramolecular processes are discussed, with special emphasis on the regio‐, chemo‐, and stereoselectivity issues, as well as natural products syntheses. A comprehensive representation of experimental data is accompanied by critical analyses to give a reader adequate ideas of the current status of this field, of what and can be achieved, of what can be anticipated in any new reaction or in any new application of a known process, and of predictions that can be made based on the collective accumulated knowledge. Discussions of oxidations of unsaturated compounds such as arenes and alkenes, of the α‐acetoxylation and α‐chlorination of ketones, and of chlorination of alkenes are beyond the scope of this review.