Selective and synergistic cobalt(III)-catalyzed three-component C–H bond addition to dienes and aldehydes

Two-component C–H bond additions to a large variety of coupling partners have been developed with applications towards materials, natural product and drug synthesis. Sequential three-component C–H bond addition across two different coupling partners potentially enables the convergent synthesis of complex molecular scaffolds from simple precursors. Here, we report three-component Co(III)-catalyzed C–H bond additions to dienes and aldehydes that proceeds with high regio- and stereoselectivity resulting in two new carbon-carbon σ-bonds and from four to six new stereocenters. The reaction relies on the synergistic reactivity of the diene and aldehyde with neither undergoing C–H bond addition alone. A detailed mechanism is supported by X-ray structural characterization of a Co(III)-allyl intermediate, observed transfer of stereochemical information, and kinetic isotope studies. The applicability of the method to biologically relevant molecules is exemplified by the rapid synthesis of the western fragment of the complex ionophore antibiotic lasalocid A.