Highly stereoselective synthesis of 1,4-bifunctional compounds was accomplished via Carreira's asymmetric alkynylation to α-oxyaldehyde followed by regio- and stereoselective Pd-catalyzed allylic substitution reaction. The stereogenic center at the protected chiral secondary alcohol not only works as a stereocontroller in the first step but also controls the regiochemistry in this reaction. Upon treatment with 10 mol % of Pd(PPh3)4 and two equivalents of nucleophile (Nu = NaCH(CO2Me)2, BnNH2), both E- and Z-allylic trifluoroacetates underwent stereospecific chirality transfer to the distal position, giving anti- and syn-1,4-bifunctional compounds, respectively, in good yield and with very high diastereoselectivity (>97:3 dr).
