Synthesis of α-Quaternary Amides via Cp*Co(III)-Catalyzed Sequential C-H Bond Addition to 1,3-Dienes and Isocyanates.

The synthesis of sterically congested amides was accomplished via Cp*Co(III)-catalyzed sequential C-H bond addition to 1,3-dienes followed by aminocarbonylation with isocyanates, a coupling partner that had never been utilized in sequential C-H bond addition reactions. A variety of C-H bond reactants, internally substituted dienes, and aromatic isocyanates provided secondary amide products incorporating α-all-carbon quaternary centers. The conversion of the amide products to other useful compound classes was also demonstrated.

Three-component carboformylation: α-quaternary aldehyde synthesis via Co(iii)-catalysed sequential C-H bond addition to dienes and acetic formic anhydride.

All carbon α-quaternary aldehydes are prepared via Co(iii)-catalysed sequential C-H bond addition to dienes and acetic formic anhydride, representing a rare example of intermolecular carboformylation. A wide range of internally substituted dienes containing diverse functionality can be employed in this reaction, affording complex α-quaternary aldehydes that would not be accessible via hydroformylation approaches. Mechanistic investigations, including control reactions and deuterium labeling studies, establish a catalytic cycle that accounts for formyl group introduction with an uncommon 1,3-addition selectivity to the conjugated diene. Investigations into the role of the uniquely effective additive Proton Sponge® were also conducted, leading to the observation of a putative, intermediate Co(i) tetramethylfulvene complex at low temperatures via NMR spectroscopy. The synthetic utility of the aldehyde products is demonstrated by various transformations, including proline-catalysed asymmetric aldol addition, reductive amination, and the asymmetric synthesis of amines using tert-butanesulfinamide technology.