Chemo-, Stereo- and Regioselective Fluoroallylation/Annulation of Hydrazones with gem-Difluorocyclopropanes via Tunable Palladium/NHC Catalysis

Abstract

Defluorinative manipulation of polyfluorinated molecules has shown great promise due to its granting of synthetic versatility to inert C-F bonds. The development of chemo-, stereo- and regioselective strategies to realize highly efficient formation of either the linear/branched or E/Z products from gem-difluorocyclopropanes (gem-F(2)CPs) is a challenging task. Herein, we have realized palladium/NHC-catalyzed fluoroallylation/annulation of hydrazones with gem-F(2)CPs that incorporate the hydrazone N-2 moiety into the products. The thermodynamically unstable fluorinated E-allylation products with aryl ketone hydrazones were obtained for the first time, while the di-alkyl ketone hydrazones yielded the monofluorinated products with branched selectivity under similar reaction conditions. With aldehyde hydrazones, two kinds of pyrazoles were obtained via a defluorinative allylation/annulation cascade, in which different carbon atoms of gem-F(2)CPs could be incorporated into the pyrazole rings regiospecifically. DFT calculations revealed that the divergent selectivity was kinetically controlled and the final C-C bond formation proceeded through a 7-membered TS.

Publisher

Wiley

Publication Date

6-5-2023

Publication Title

Angewandte Chemie: International Edition

Department

Chemistry and Biochemistry

Document Type

Article

DOI

https://doi.org/10.1002/anie.202303271

Keywords

C-F bond cleavage, Gem-difluorocyclopropane, Hydrazone, Pyrazole, Regioselectivity

Language

English

Format

text

Link to Full Text

Share

COinS