Abstract
<jats:p>Difluorocarbene precursors have recently garnered significant attention as versatile C1 synthons for a range of transformations. Among these, carbonylative processes are proposed to proceed via in situ generation of free CO from the difluorocarbene unit, although the origin of CO in these transformations remains unresolved. We present a comprehensive mechanistic investigation of a Pd-catalyzed multicomponent reaction (MCR) involving aryl iodides, alkynes, and BrCF2CO2K wherein the choice of ligand governs the divergent synthesis of γ-butenolides and ynones. Using state-of-the-art density functional theory (DFT) methods, we delineate the reaction landscape and factors governing ligand governed divergent reactivity in a Pd-catalyzed multicomponent coupling of aryl iodides, alkynes, and BrCF2CO2K. We reveal that the formation of Pd(II)-difluoroaryl species (Pd–CF2Ar) is favored over CO formation as proposed in literature. The resulting Pd(II)–CF2Ar intermediate constitutes a common mechanistic branching point determining product selectivity: conventional reductive pathway in presence of base and alkyne produce ynone product, whereas homolytic Pd–C bond cleavage to generate a difluoroaryl radical followed by radical addition of alkynes produce γbutenolides. The computed activation energy barriers of the competing pathways explain the experimentally observed ligand-controlled divergence. Additionally, the finding highlights the formation of difluoroaryl radicals from the BrCF2CO2K precursors for alkyne insertion. Overall, in this study, we have proposed an alternative role of Pd–difluorocarbene intermediate, one which is not proposed in prior works, and establish a mechanistic framework involving various transient Pd(II)-difluoroaryl and Pd(II)-difluoroalkyl intermediates to explain Pdcatalyzed difluorocarbene-transfer reactions. The study provides guiding principles for the rational design of new ligands to access diverse transformations and broaden the chemical space of Pd-catalyzed difluorocarbene-transfer chemistry.</jats:p>