Flavin-dependent catalysts are widely applied to aerobic monooxygenation/oxidation reactions. In contrast, flavin-catalyzed aerobic dioxygenation reactions exhibit higher atomic economy but are less reported, not to mention the relevant mechanistic studies. Herein, a density functional theory study on flavin-catalyzed aerobic epoxidation-oxygenolysis of alkenyl thio-esters was performed for the first time. Different from the previous mechanistic proposal, a pathway featuring two catalytic stages, monoanionic flavin-C(4a)-peroxide/oxide intermediates, and a reverse reaction sequence (epoxidation goes prior to oxygenolysis) was revealed. In comparison, the pathways involving dianionic flavin catalysts, monoanionic flavin-N(5)-(hydro)peroxide/C-(10a)-peroxide, or neutral flavin-C(4a)-hydroper...

DFT calculations are carried out to investigate the hydroacylation mechanism based on copper-catalyzed A3- coupling tandem reaction of terminal alkynes, aldehydes and amines. The study reveals significant mechanistic differences between copper(I) and copper(II) catalysts. In the Cu(II)-catalyzed system, incorporation of a ligand is deemed necessary for facilitating reactivity, whereas no ancillary ligand is required in Cu(I) system. The ligand, through coordination with the Cu(II) center, stabilizes the key transition states and intermediates, resulting in a substantial reduction in the activation barrier. The ligand exhibits varying effect, with the order of activity being piperidine > pyridine > DMSO, correlating positively with the interaction energy between ligand and Cu complex. Addit...

Developing applicable methods to forge linkages between sp3 and sp2-hydridized carbons is of great significance in drug discovery. We show here a new, Ni-catalyzed reductive crosscoupling reaction that forms Csp3−Csp2 bonds from aryl iodides and cyclic sulfonium salts. Notably, Csp3−Csp2 bonds can be forged selectively at the iodine-bearing carbon of bromo(iodo)arenes which is usually recognized as a huge challenge under the catalytic reductive cross-coupling (CRCC) conditions. Experimental and computational mechanistic studies support LNiIAr as an active species, while the untraditional anti-Markovnikov selective alkylation of asymmetric sulfonium salts is determined by the oxidative S-substitution of sulfonium salts with LNiIAr. This protocol further expands the range of alkyl electrophi...

An unprecedented transient promotion function (TPF) of CO2 in the electrochemical hydrogenation/deuteration of imines (especially α-iminonitriles) is reported. The TPF influence of CO2 results from the introduction of CO2 that disperses the negative charges of the imine radical anion intermediate. The resulting redistribution of electrons leads to a lower reduction potential of the CO2-substituted imine radical anion and thus facilitates the succeeding one-electron reduction. CO2 is finally released via spontaneous decarboxylation to complete the transient promotion process.

We report an unprecedented transition-metal-free method to access diverse non-symmetric azo derivatives via cross-couplings of arylazo sulfones with Csp2–H and Csp3–H bonds. Instead of serving as aryl radical precursors, arylazo sulfones demonstrate the unexplored potential of being stable electrophilic diazo sources that easily undergo arylation and alkylation under basic conditions, and enhance the atom utilization efficiency. Compared with the low-stability diazonium salts, the relatively stable arylazo sulfones also offer the advantage of being suitable for large -scale storage. This strategy exhibits merits such as simple operation, mild conditions, transition-metal-free process, broad substrate scopes, and good air compatibility. Mechanistic studies on the functionalization of arylaz...

Highly effective and selective noble metal-free catalysts attract significant attention. Here, a single-atom iron catalyst is fabricated by saturated adsorption of trace iron onto zeolitic imidazolate framework-8 (ZIF-8) followed by pyrolysis. Its performance toward catalytic transfer hydrogenation of furfural is comparable to state-of-the-art catalysts and up to four orders higher than other Fe catalysts. Isotopic labeling experiments demonstrate an intermolecular hydride transfer mechanism. First principles simulations, spectroscopic calculations and experiments, and kinetic correlations reveal that the synthesis creates pyrrolic Fe(II)-plN3 as the active center whose flexibility manifested by being pulled out of the plane, enabled by defects, is crucial for collocating the reagents and ...

Site-selective C−H fluorination is an attractive strategy for directly transforming inert C−H bonds into C−F bonds, yet it remains a significant challenge. Herein, we have developed an efficient and versatile strategy for site-selective fluorination and amination of phenylalanine-containing peptides via late-stage Pd-catalyzed δ-C(sp2)-H activation, providing a valuable tool for the in situ synthesis of fluorinated indoline scaffolds within peptides.

O2, one of the ideal oxidants, suffers from low solubility, low oxidizability, low selectivity and a triplet ground state when applied in organic synthesis. Biomimetic copper catalysis has been demonstrated to be a powerful method for activating and transforming O2 to conduct aerobic reactions for a long time. On the other hand, the structures of Cu–O2 complexes are complex with diverse downstream reactions, whereas active copper intermediates were rarely identified by experimental methods, making the mechanisms of many Cu-catalyzed aerobic reactions far from clear. In this context, computational studies emerged as an effective alternative to mechanistic studies on Cu-catalyzed aerobic reactions. This review introduces the relevant computational studies since 2012, focusing on showing the ...

The remote C(sp3)-H activation/functionalization via 1,5-Pd migration involved in the Pd(0)-catalyzed reaction of (8-bromonaphthalen-1-yl)trimethylsilane (S1) and N-tosylhydrazone (S2) was theoretically investigated with the aid of the density functional theory calculations. The role of the Lewis base LiOtBu was revealed by forming a Pd-O bond to participate in the reaction. The remote C(sp3)-H activation was found to be accomplished by concerted Pd-C(sp2)/C(sp3)-H σ-bond metathesis rather than by stepwise C(sp3)-H oxidative addition/C(sp2)-H reductive elimination. Additionally, the mechanism of generating 2-diazopropane from N-tosylhydrazone (S2) was investigated. This study would be informative and benefit to designing novel relevant transition-metalcatalyzed remote C-H activation/functi...

The mechanism of the rhodium-catalyzed C−H alkenylation/directing group migration and [3+2] annulation of Naminocarbonylindoles with 1,3-diynes has been investigated with DFT calculations. On the basis of mechanistic studies, we mainly focus on the regioselectivity of 1,3-diyne inserting into the Rh−C bond and the N-aminocarbonyl directing group migration involved in the reactions. Our theoretical study uncovers that the directing group migration undergoes a stepwise β-N elimination and isocyanate reinsertion process. As studied in this work, this finding is also applicable to other relevant reactions. Additionally, the role of Na+ versus Cs+ involved in the [3+2] cyclization reaction is also probed.