Synthesis of Both Enantiomers of Nine‐Membered CF3‐Substituted Heterocycles Using a Single Chiral Ligand: Palladium‐Catalyzed Decarboxylative Ring Expansion with Kinetic Resolution

Abstract

AbstractThe 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.