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

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 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.

Asymmetric Radical-Type 1,2-Alkoxy-Sulfenylation of Benzoxazole-2-Thiols to Vinylarenes Catalyzed by Chiral Vanadyl Complexes

“…Similar to Prof. Liu’s study, 2 and 3° alcohols like 2-propanol, t -butanol, and Me 3 SiOH did not work in our catalytic system, presumably due to steric reasons. Both N -hydroxyphthalimide and phenols have been utilized as stoichiometric radical trapping agents in 2-propanol in our previous studies. , The current catalytic protocol can also be applied with reduced loadings of the 1° alcohols from 123.5 equiv of MeOH as a solvent (2 mL) at 0 °C to 10 equiv of MeOH in CH 2 Cl 2 (2 mL), along with increasing loading of catalyst- 4c to 10 mol %. Under such circumstances, desired product 3a was isolated in a moderate yield of 44% and in 91% ee (Supporting Information).…”

“…At the current stage, the only asymmetric version of the radical type process by common arenethiols was recently realized by Prof. Chemler and Burde using chiral Cu­(I/II)-bisoxazoline complexes in an intramolecular manner (Scheme B). , The reactions proceeded with intramolecular asymmetric alkene oxycupration, followed by trapping of the arylsulfenyl group from a given diaryl disulfide at 120 °C. In view of our recent success in asymmetric intermolecular 1,2-alkoxyphosphinoylation of vinylarenes − (Scheme C) and the pending challenge of using REW heteroarene-thiols in asymmetric 1,2-difunctionalization of alkenes, we sought to develop the first asymmetric intermolecular variant of this type (Scheme D). In addition, the resulting products may exhibit potential anti-Alzheimer , and anti-Candida activities (Scheme E) …”