RESUMO
A novel enantioselective Tsuji-Trost-type cross coupling reaction between gem-difluorinated cyclopropanes and N-unprotected amino acid esters enabled by synergistic Pd/Ni/chiral aldehyde catalysis is presented herein. This transformation streamlined the diversity-oriented synthesis (DOS) of optically active α-quaternary α-amino acid esters bearing a linear 2-fluoroallylic motif, which served as an appealing platform for the construction of other valuable enantioenriched compounds. The key intermediates were confirmed by HRMS detection, while DFT calculations revealed that the excellent enantioselectivity was attributed to the stabilizing non-covalent interactions between the Pd(II)-π-fluoroallyl species and the Ni(II)-Schiff base complex.
RESUMO
We herein disclose the Pd/amine dual-catalyzed ring-opening cross-coupling reaction between gem-difluorinated cyclopropanes (gem-F2CPs) with aldehydes, which enables the diversity-oriented synthesis (DOS) of 2-fluoroallylic aldehydes bearing all-carbon quaternary centers with features of broad scope and excellent functional group tolerance. The synthetic value of this Tsuji-Trost system was further demonstrated by late-stage functionalization of natural product-derived gem-F2CPs and the diverse synthesis of various fluoroallylic aldehyde derivatives, including alcohol, alkyne, alkene, and amine.