Palladium-Catalyzed Oxy-olefination of Styrenes toward Fluoroallyl Ethers

Allyl
ethers are valuable skeletons that occur widely in natural
products. They also serve as important synthetic intermediates, particularly
as precursors in Tsuji–Trost reactions. However, their fluorinated
analogues remain underexplored, despite the good recognition of fluoroalkenes
as isosteres of amides in biological chemistry. Herein, we disclosed
an expedient Pd-catalytic platform to construct fluoroallyl ethers
via oxy-olefination of easily available alkenes with alcohols and
2,2-dibromo-2-fluoroamide compounds involving a CC bond formation
process. The protocol demonstrates excellent compatibility with a
broad range of aromatic alkenes under mild reaction conditions, including
modified biomolecules and drug derivatives containing styrene motifs.
Mechanistic investigations suggest that fluoroalkyl radicals and the
π-allyl palladium complex play pivotal roles as key intermediates
in this transformation.