Direct Catalytic Asymmetric Synthesis of Trifluoromethylated γ‑Amino Esters/Lactones via Umpolung Strategy

Enabled
by the discovery of new cinchonium salts and coadditives,
a direct and efficient asymmetric access to trifluoromethylated γ-amino
esters/lactones has been realized through the enantioselective and
diastereoselective umpolung reaction of trifluoromethyl imines with
acrylates or α,β-unsaturated lactones as carbon electrophiles.
At 0.5–5.0 mol % catalyst loadings, the newly developed catalytic
system activates a variety of imine substrates as unconventional nucleophiles
to mediate highly chemo-, regio-, diastereo-, and enantioselective
C–C bond forming reactions. The developed synthetic protocol
represents an excellent strategy to target a series of versatile and
enantiomerically enriched γ-amino esters/lactones in good to
excellent yields from the readily available starting materials. Additionally,
we found that the epi-vinyl catalysts based on cinchonidine
and quinine promote a similarly high enantioselective reaction generating
the opposite configuration of chiral products in a highly efficient
manner, which allows convenient access to either the R- or S-enantiomer of the chiral amine products in
high yields and excellent enantioselectivities.