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

Abstract

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.

Weakly Coordinated Cobaltacycles: Trapping Catalytically Competent Intermediates in Cp*CoIIICatalysis

“…The inherent lack of stability has been shown to be even more problematic with first‐row metal systems, such as cobalt‐based platforms . Although important synthetic advances have been made in the field of Cp*Co III catalysis, characterizing the putative cobalt intermediates in these transformations remains challenging . This profound lack of fundamental understanding at the molecular level precludes the rational design and development of novel and more efficient Cp*Co‐catalyzed processes.…”

Synthesis of Homoallylic Alcohols with Acyclic Quaternary Centers through CoIII‐Catalyzed Three‐Component C−H Bond Addition to Internally Substituted Dienes and Carbonyls

“…Recently, our lab reported a Co III ‐catalyzed C−H bond addition to dienes and aldehydes [Figure , Eq. (1)] . In this approach, two new C−C σ bonds are formed in a regio‐ and stereoselective manner as dictated by a Co III ‐allyl chair‐like transition state.…”

“…A catalytic amount of AcOH was found to be beneficial as opposed to LiOAc or PivOH, which have been used as additives for other Co III ‐catalyzed C−H bond addition reactions. Substrate concentration was shown to play a critical role in this transformation, with 0.4 m leading to much lower conversion than 1.0 M . Heating at 50 °C was chosen as the standard conditions for isoprene addition, but 70 °C was found to be necessary for some dienes and/or carbonyl compounds bearing bulkier substituents (see below).…”

“…A mechanism is proposed based upon the studies with isotope‐labeled starting materials, the stereochemistry observed for the products, and prior mechanistic studies for three‐component coupling of butadiene (Figure ). In the presence of the Co III ‐catalyst, a reversible ortho C−H bond activation of substrate 1 through concerted metalation/deprotonation generates 5‐membered metallocycle A .…”

“…In the presence of the Co III ‐catalyst, a reversible ortho C−H bond activation of substrate 1 through concerted metalation/deprotonation generates 5‐membered metallocycle A . Alkene coordination and migratory insertion of the diene affords the η 3 ‐Co‐allyl species B . Syn β‐hydride elimination provides species C , with the syn ‐coplanar hydrogen H a incorporated as the Co hydride.…”