Diastereoselective synthesis of 2,5-disubstituted-3-hydroxy-tetrahydrofurans through a counterion-directed Tsuji–Trost reaction

Abstract

Tsuji–Trost Counterion Directed Catalysis (CDC) allows the diastereoselective synthesis of 5-alkyl-3-hydroxy-2-vinyl tetrahydrofurans in high yields using easily accessible 4,6-dihydroxyalk-2-en-1-yl esters as substrates. The mechanism of this reaction has been investigated by relying on DFT predictions and experimental confirmations based on deuterium labeling and modification of the pK_a of counterions which demonstrates that the favored transition state is tightly organized through the formation of a network of H-bonds.