Asymmetric Cross Couplings of Trifluoromethyl Radical to Vinylarenes with N-Hydroxy-oxazinediones and Subsequent Aerobic Oxidative Homocoupling of 2-Naphthols Catalysed by Chiral Vanadyl Complexes

Asymmetric three-component, 1,2-aminoxy-trifluoromethylation of styrenes with N-hydroxy-1,3-benz/naphthoxazine-2,4-diones (i. e., N-OH-(B/Np)OxzOn) catalysed by chiral vanadyl complexes derived from N-salicylidene-L-t-leucinate were explored. Among 14 different solvents and 13 different catalysts screened, the best reaction scenarios were in 2-propanol with 3-(2,5-dimethyl)phenyl-5-bromo (DMP), or 3-t-butyl-5-bromo substituted catalysts that led to the corresponding complementary (R)- and (S)-products with potential biological activities in 45-91% yields and up to 85 and 75% ee, respectively. Further optimisation with the DMP catalyst led to the best combination of 3-halo/3,5-dihalo-styrenes with 6-/7-Br-N-OH-(B/Np)OxzOn as the trapping agents. The corresponding eight different products were isolated in 52-75% yields with ees in a range of 88-93% (R). Based on Density Functional Theory (DFT) calculations with conformational searches, the origin of enantiocontrol and the working mechanism were proposed by resorting to a bidentate-chelation between the amide or carbamate C=O group and N-OH group in the trapping agent to the vanadyl center followed by asymmetric benzylic radical trapping in an S(H)2 fashion. Subsequent Fragment Molecular Orbital (FMO)/Pair Interaction Energy Decomposition Analysis (PIEDA) calculations with the DMP catalyst were carried out to rationalize the extent of asymmetric induction. One representative product derived from p-methyl-styrene and NpOxzOn was hydrolyzed in basic MeOH with decarboxylation to unmask its carbamate moiety. The resulting chiral (R)-N-benzoxy-3-hydroxy-2-naphthamide was subjected to aerobic, oxidative homo-coupling catalysed by the DMP catalyst in CCl4. The corresponding 2,2-binaphthol product was isolated in 90% (brsm) yield with nearly complete diastereo-control at the created (M)-axial chirality, allowing for sequential, bi-functional asymmetric cross-coupling applications.