Cu2O−CD nanosuperstructures as a Biomimetic Catalyst for Oxidation of Benzylic sp3 C−H bonds and Secondary Amines using Molecular Oxygen: First Total Synthesis of proposed Swerilactone O

Abstract

AbstractCu2O−cyclodextrin (Cu2O−CD) nanosuperstructures catalyzed oxidation of benzylic sp3 C−H bonds and secondary amines via C−H bond activation is demonstrated in this protocol. Cu2O−CD nanosuperstructures displayed excellent catalytic activity for the oxidative transformation of substrates in combination with a radical promoter N‐hydroxyphthalimide (NHPI) and molecular oxygen as the green oxidant to afford the corresponding oxidized products with high selectivity and excellent yields. Moreover, the nanosuperstructures were found to be stable during the reaction, easy to recover, and recyclable up to three cycles to afford the products consistently with no loss of catalytic activity. The remarkable feature of this protocol is that the catalyst Cu2O−CD remained intact even after three cycles without undergoing over‐oxidation or any phase changes. The phase purity of Cu2O was ascertained by various characterization techniques such as X‐ray diffraction (XRD), Scanning electron microscopy (SEM), High‐resolution transmission electron microscopy (HRTEM), X‐ray photoelectron spectroscopy (XPS), Thermogravimetric analysis (TGA), and Inductively coupled plasma atomic emission spectroscopy (ICP‐AES) analysis. Furthermore, to gain more detailed insights into the reaction mechanism, oxygen labelled catalyst i. e., Cu218O−CD nanosuperstructures were synthesized using H218O (18‐labelled water) to determine any possible dioxygen exchange mechanism operative by Cu218O oxide thereby ascribing the source of oxygen in the reaction. Several other control experiments such as Electron Spin Resonance (ESR) and radical quenching studies established the mechanism to traverse a radical pathway. Additionally, the developed Cu2O−CD catalyst was also showcased to efficiently mimic the activity of the enzyme (S)‐tetrahydroprotoberberine oxidase (STOX) for the biomimetic synthetic transformation of tetrahydropalmatine to palmatine hydroxide. Interestingly, the developed Cu2O−CD mediated benzylic oxidation was used as a key step for the first total synthesis of the natural product Swerilactone O, an unusual secoiridoid with unprecedented C13 skeleton wherein aldol condensation reaction followed by oxidation afforded the natural product in 69% yield for overall steps. The utility of benign, supramolecular, and recyclable catalyst Cu2O−CD for oxidative transformations under aerobic conditions endorses the sustainability of the developed protocol.