Copper-Catalyzed Ring-Opening Defluorinative Alkylation of Siloxydifluorocyclopropanes: Synthesis of γ-Fluoro-δ-Ketoesters and γ,δ-Diketonitriles

Abstract

In view of the importance of both fluorinated synthons and homoenolate equivalents, synthetic application of difluorocyclopropanols is desired but remains challenging due to their thermodynamic instability. Herein, we use siloxydifluorocyclopropanes as difluorocyclopropanol precursors to carry out new Cu-catalyzed ring-opening defluorinative alkylation. With αbromo carboxylic esters as coupling partners, the reaction affords γ-fluoro-δketoesters via a Cu I /Cu II catalytic cycle. Interestingly, by the use of αbromoamides, the ring-opening defluorinative alkylation is followed by an additional intramolecular C−N oxidative coupling to deliver a lactam intermediate, which further undergoes defluorination, hydrolysis, ring opening, and dehydration cascade via a Cu I / Cu II /Cu III catalytic pathway, leading to γ,δ-diketonitriles as the final products.

A convenient transformation of alkynes to α-hydroxy-α-CF3-γ-ketoester derivatives via H3PO4-catalyzed tandem hydration and aldol condensation

“…It is well known that trifluoropyruvate is one of the most versatile fluorine-containing building blocks 5 and contributes greatly to applications in organic synthesis. 6 The carbonyl–ene reaction of trifluoropyruvate with styrene derivatives would provide the corresponding quaternary trifluoromethyl-substituted α-hydroxy esters with high regioselectivity and stereoselectivity (Scheme 1a).…”

Bicyclization of 4-Cyano-1,2-diketones with Amidines: Synthesis of Tetrahydroimidazo[4,5-b]-5-pyridinones

“…Recently, a series of 4-cyano-1,2-diketones were synthesized by a copper-catalyzed ring-opening defluoronative cross-coupling reaction between siloxydifluorocyclopropanes and α-bromoamides in our group . The cyano group has a wide range of functionalities in the constructions of acids, amides, imines, N -heterocycles, and so forth .…”