Synthesis of Both Enantiomers of Nine-Membered CF₃ -Substituted Heterocycles Using a Single Chiral Ligand:...

The two enantiomers of trifluoromethyl-benzo[c][1,5]oxazonines, (R)-4 and (S)-4, can be selectively accessed with high enantiopurity by the Pd-catalyzed ring-expansion reaction of trifluoromethyl-benzo[d][1,3]oxazinones (1) with vinyl ethylene carbonates (3) using one antipode of a chiral ligand. Initially, the reaction proceeds by a double decarboxylative ring-expansion with kinetic resolution of 1 in the presence of a Pd-catalyst/chiral ligand to provide (R)-4 with high enantiopurity. At the same time, the nonreactive antipode of 1, (S)-1, which was recovered with an impeccable s factor of up to 713 and an ideal chemical yield, was transferred into the antipode of the products, (S)-4, with high enantiopurity by a second run of the Pd-catalyzed double decarboxylation reaction, but this time without any chiral auxiliary. Thus, both antipodes of the chiral trifluoromethyl heterocycles 4 can be obtained in excellent enantiopurity using only a single antipode of the chiral catalyst.