Cp*Co(III)-Catalyzed Coupling of Benzamides with α,ß-Unsaturated Carbonyl Compounds: Preparation of Aliphatic Ketones and Azepinones.

A Cp*CoIII -catalyzed C-H functionalization of benzamide substrates with α,ß-unsaturated ketones has been optimized, providing a facile route towards aliphatic ketone products. When employing α,ß-unsaturated aldehydes as coupling partners, under the optimized protocol, a cascade reaction forming azepinones has also been developed. Finally, DFT studies have demonstrated how stabilization of a metallo-enol intermediate when employing α,ß-unsaturated ketones is the driving force leading to the observed aliphatic ketone product rather than olefinic products reported using α,ß-unsaturated esters as coupling partners.

A challenging redox neutral Cp*Co(III)-catalysed alkylation of acetanilides with 3-buten-2-one: synthesis and key insights into the mechanism through DFT calculations.

Traditional, established palladium cross-coupling procedures are widely applied in complex molecule synthesis; however, there is a significant disadvantage in the requirement for pre-functionalised substrates (commonly halides/triflates). Direct C-H activation protocols provide the opportunity for a novel approach to synthesis, although this field is still in its relative infancy and often transferability between substrate classes remains unresolved and limitations not fully understood. This study focuses on the translation of an established Cp*Co(III)-catalysed alkylation of benzamides to related acetanilides using 3-buten-2-one as coupling partner. The developed procedure provides a wide substrate scope in terms of substituted acetanilides, although the optimised conditions were found to be more forcing than those for the corresponding benzamide substrates. Interestingly, density functional theory (DFT) studies reveal that the major impediment in the mechanism is not the C-H activation step, but instead and unexpectedly, effective competition with more stable compounds (resting states) not involved in the catalytic cycle.

Recent advances using [Cp*Co(CO)I2] catalysts as a powerful tool for C-H functionalisation.

Expansion of the synthetic chemists' toolbox is currently a topic of great interest, with successes providing access to novel compounds and more efficient routes towards new and known pharmaceuticals and agrochemicals. In this context, the development and application of first-row transition metal-catalysed C-H functionalisation protocols is seen as a key opportunity. This perspective provides a brief background of the discovery and application of high-valent cobalt-catalysis in C-H functionalisation, before detailing examples of recent advances in this field using the powerful [Cp*Co(CO)I2] catalysts for both terminal couplings and heterocycle formation. Finally, a discussion on the detection and isolation of elusive reactive intermediates in high-valent cobalt-catalysed C-H functionalisation, shedding light on how these catalyst systems operate, will be provided.