Ligand-controlled regioselective and chemodivergent defluorinative functionalization of gem-difluorocyclopropanes with simple ketones

Abstract

A robust Pd/NHC ligand synergistic strategy that enables the exquisite regioselective and chemodivergent C–F bond functionalization of gem-difluorocyclopropanes with simple ketones, is reported.

Recent Advances in Transition-Metal-Catalyzed Cross-Coupling Reactions of gem-Difluorinated Cyclopropanes

“…Scheme 12 Palladium-catalyzed reactions of gem-difluorinated cyclopropane with hydrazone to form branched products Soon after, this strategy was further adopted by the group of Lv and Li to achieve a palladium-catalyzed branched selective coupling of gem-difluorinated cyclopropanes with simple ketones (Scheme 13). 25 In this reaction, an oxo-bis(η 1 -allyl) palladium was proposed as the key intermediate, which would undergo a similar inner sphere 3,3'-reductive elimination to give γ,δ-unsaturated ketone with branched selectivity. Again, the intrinsic ambident nucleophilic property of the enolate species and the bulky NHC ligand are crucial for the branched selectivity.…”

Diversity‐Oriented Metal‐Free Synthesis of Nitrogen‐Containing Heterocycles Using Atropaldehyde Acetals as a Dual C3/C2‐Synthon

“…Also, how to finely regulate the reactivity and selectivity of versatile reagents to overstep inherent bias from a constitutively complicated system, generating a novel and specific bond-forming mode is of considerable challenge. [3] In this context, the development of novel and easily available bifunctional synthons, as one of the innovative strategies, to assemble skeletally diverse heterocyclic frameworks has been a fascinating theme. In such a strategy, different reactivities of one reagent converging together via tandem reactions can not only enrich the diversity and complexity of products, but also minimize side reactions by reducing the variety of starting materials, which can comply well with the criteria of green chemistry.…”

Cobalt-Catalyzed Fluoroallyllation of Carbonyls via C–C Activation of gem-Difluorocyclopropanes

“…Highly strained gem -difluorinated cyclopropanes (FCPs) are privileged substrates for the construction of fluorinated compounds . Since Fu and co-workers reported the pioneering work on the palladium-catalyzed ring opening of gem -FCPs and their coupling with N - and O -nucleophiles to forge monofluorinated alkene scaffolds, palladium- and rhodium-catalyzed transformations of this strained skeleton have been elegantly explored, wherein the electrophilic π-allylmetals generated by sequential C–C and C–F cleavage could react with an array of nucleophiles, including boronic acids, hydrazine, organometallics, enolate, sodium benzenesulfinate, terminal alkynes, and arenes (Scheme b). However, due to highly electrophilic property of the formed fluoroallylmetal species, the transformation of such electron-deficient complexes, especially those generated by earth-abundant inexpensive transition metals, with electrophiles remained undisclosed.…”