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

Chemical Science Pub Date: 2022-11-21 DOI: 10.1039/D2SC05599F

Abstract

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.

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