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

Abstract

AbstractAsymmetric 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 SH2 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.