C–C Bond Forming Reactions Enabled by Vitamin B₁₂─Opportunities and Challenges

Abstract

Cobalt not only is an essential micronutrient for mammals but also marks itself as important in organic synthesis, especially in the field of catalysis. Various useful reactions, such as alkene hydroformylation, hydrogenation, heterofunctionalizations of carbon−carbon double bonds, C−H activation, and crosscoupling reactions, have been realized with the aid of this metal. At the same time, cobalt deserves special attention as a catalyst for radical processes; in fact, in the form of vitamin B 12 , it was designed by Nature as a reversible carrier for radicals. Since this molecule is a native Co-complex, it is very attractive for the development of sustainable transformations, and it has already been demonstrated that vitamin B 12 and its derivatives mediate numerous reactions that have found applications in both the construction of complex molecules and the degradation of polyhalogenated pollutants. However, in this Perspective, we focus the readers' attention on radical C−C bond forming reactions catalyzed by vitamin B 12 , which are particularly important as a tool for the synthesis of important molecules in a greener manner. We also ponder over the challenges that remain to be addressed and the solutions that are expected to come.

Ligand‐to‐Metal Charge Transfer (LMCT) Photochemistry at 3d‐Metal Complexes: An Emerging Tool for Sustainable Organic Synthesis

“…This mode of catalytic polar‐radical hybrid reactivity has also been demonstrated with vitamin B12 derivatives [155,156] . For example, the groups of Gryko and Komeyama have independently reported intermolecular reactions between alkyl tosylates or S‐acyl thiopyridines with electron deficient olefins to give Giese‐type products under blue LEDs irradiation (Scheme 35).…”

“…Although other related photoinduced reactions such as decarboxylation [150,151] have been know at a fundamental level for decades, the synthetic applications of photochemical processes in Co(III) have been largely dominated by the facile C−Co homolysis upon LMCT excited‐states population [152–154] at vitamin B12‐derivatives and bis(dimethylglyoximato) complexes, also known as cobaloximes (Scheme 31A). In this section there are summarized some of the most representative examples to provide a general vision of the field, however for a more comprehensive analysis the reader is referred to any of the excellent reviews on these types of catalysts that are reported elsewhere [155–159] . The general reactivity profile of these compounds under photocatalytic conditions is depicted in Scheme 31B [153] .…”

“…In this section there are summarized some of the most representative examples to provide a general vision of the field, however for a more comprehensive analysis the reader is referred to any of the excellent reviews on these types of catalysts that are reported elsewhere. [155][156][157][158][159] The general reactivity profile of these compounds under photocatalytic conditions is depicted in Scheme 31B. [153] Co(III)À alkyl complexes can be generated following two major pathways: (i) polar S N 2-type reaction of Co(I) precursors with alkyl electrophiles and other related systems (e. g. epoxides) or (ii) C-radical capture by stable, longlived Co(II) metalloradicals.…”

“…This mode of catalytic polar-radical hybrid reactivity has also been demonstrated with vitamin B12 derivatives. [155,156] For example, the groups of Gryko and Komeyama have independently reported intermolecular reactions between alkyl tosylates or S-acyl thiopyridines with electron deficient olefins to give Giese-type products under blue LEDs irradiation (Scheme 35). [164,165] Those reactions are based on the faculty of these Co(I) "supernucleophiles" to participate in S N 2-type reactions and subsequent photoinduced LMCT homolysis.…”

Intercepting Hydrogen Evolution with Hydrogen-Atom Transfer: Electron-Initiated Hydrofunctionalization of Alkenes

“…Baran et al demonstrated electroreductive generation of Co III –H in the context of alkyne hydrogenation, alkene isomerization, and related transformations . Nevertheless, the exploration of such strategies in synthetic contexts remains rare beyond these examples . In this work, we employed analytical and synthetic tools to study a family of electronically distinct Co­(salen) complexes and obtained qualitative and quantitative insights into the electroreductive generation of Co III –H and its reaction with alkenes (Scheme A).…”