Understanding Off‐Cycle and Deactivation Pathways in Radical‐Type Carbene Transfer Catalysis

Abstract

Transition metal radical‐type carbene transfer catalysis is a sustainable and atom‐efficient method to generate C−C bonds, especially to produce fine chemicals and pharmaceuticals. A significant amount of research has therefore been devoted to applying this methodology, which resulted in innovative routes toward otherwise synthetically challenging products and a detailed mechanistic understanding of the catalytic systems. Furthermore, combined experimental and theoretical efforts elucidated the reactivity of carbene radical complexes and their off‐cycle pathways. The latter can imply the formation of N‐enolate and bridging carbenes, and undesired hydrogen atom transfer by the carbene radical species from the reaction medium which can lead to catalyst deactivation. In this concept paper, we demonstrate that understanding off‐cycle and deactivation pathways not only affords solutions to circumvent them, but can also uncover novel reactivity for new applications. In particular, considering off‐cycle species involved in metalloradical catalysis can stimulate further development of radical‐type carbene transfer reactions.

Light Induced Cobalt(III) Carbene Radical Formation from Dimethyl Malonate As Carbene Precursor

“…It was found that with an excess of iodonium ylide, a biscarbene complex was formed that transferred the carbene moiety onto the double bond, forming cyclopropane with high yields and short reaction times (up to 99%, < 5 min). In this work, the general sensitivity of metal carbene radical complexes toward deactivation was also observed: most metal carbene radical complexes are very competent in abstracting a hydrogen from weak C–H bonds . Contrarily, the group of Che showed that the hydrogen atom transfer (HAT) reaction can actually be used to generate the desired active radical species, thereby leading to product formation rather than deactivation …”

“…In this work, the general sensitivity of metal carbene radical complexes toward deactivation was also observed: most metal carbene radical complexes are very competent in abstracting a hydrogen from weak C−H bonds. 20 Contrarily, the group of Che showed that the hydrogen atom transfer (HAT) reaction can actually be used to generate the desired active radical species, thereby leading to product formation rather than deactivation. 21 However, all of the above-mentioned reactions require highenergy carbene precursors bearing excellent leaving groups to generate the reactive carbene radical intermediate (Figure 1a).…”

Light Induced Cobalt(III) Carbene Radical Formation from Dime-thyl Malonate as Carbene Precursor

“…In this work, the general sensitivity of metal carbene radical complexes toward deactivation was also observed: most metal carbene radical complexes are very competent in abstracting a hydrogen from weak C-H bonds. 20 Contrarily, the group of Che showed that the hydrogen atom transfer (HAT) reaction can actually be used to generate the desired active radical species, thereby leading to product formation rather than deactivation. 21 However, all of the above-mentioned reactions require highenergy carbene precursors bearing excellent leaving groups to generate the reactive carbene radical intermediate (Figure 1a).…”

Mingling Light, Oxygen, and Organometallics to Form Cobalt–Carbon Bonds in the Confines of a Metal–Organic Nanocage

“…In one notable study, de Bruin and Reek increased the turnover numbers (TONs) of cyclopropanations and intramolecular CH activations by confining a cobalt-porphyrin catalyst in a large nanocube ( 1 ) comprising six porphyrin walls bound together by eight (bipy) 3 Fe 2+ (bipy = 2,2′-bipyridine) vertices that are connected to the porphyrins via imine linkages (Scheme A) . These connections are dynamic enough to allow uptake of a [(4-pyridyl) 4 porphyrin]­Co II guest (TPyPCo II ), providing a way to isolate this catalyst inside the cube to stabilize radical-carbene ligands against detrimental radical dimerizations. , This example exclusively involves metal-bound radicals, in contrast to the fully organic radical intermediates generated by H atom abstraction or M–C homolysis. The ability of artificial porous materials to guide the reactivity of free alkyl radicals may, however, be responsible for the improved selectivity of C–H halogenations in a metal–organic framework reported by Li and Zhou, though we can only speculate since no mechanistic details were examined …”