Palladium-catalyzed Z-selective alkynylation of gem-difluoro alkenes via carbon–fluorine bond activation: mechanistic insights into oxygen-directed regiocontrol

Abstract

In organofluorine chemistry, the synthesis of fluorinated amino acids requires new synthetic methods. Here, we report a carbon–carbon coupling strategy using fluoroamino acid-derived substrates that delivers Z-configured alkenes with high selectivity. Stereocontrol is achieved through coordination of the amino acid oxygen to the palladium center. The mechanism was elucidated through systematic pathway analysis, isolation of key intermediates, and computational studies. Beyond providing a route to Z-fluoro dehydroalkynyl amino acids, this work illustrates how amino acid motifs can serve as directing elements in catalysis. These insights support the rational design of fluorinated amino acid derivatives for synthetic and pharmaceutical applications.