Mechanistic Insights into Oxidation of Benzaldehyde by Co-Peroxo Complexes.

Transition metal-peroxide complexes play a crucial role as intermediates in oxidation reactions. To unravel the mechanism of benzaldehyde oxidation by the Co-peroxo complex, we conducted density functional theory (DFT) calculations. The identified competing mechanisms include nucleophilic attack and hydrogen atom transfer (HAT). The nucleophilic attack pathway involves Co-O cleavage and nucleophilic attack, leading to the formation of the benzoate product. And the HAT pathway comprises O-O cleavage and HAT, ultimately resulting in the benzoate product. DFT calculations revealed that the formation of the end-on Co-superoxo complex 2 through Co-O cleavage, starting from the side-on Co-peroxo complex 1, is much more favorable than the formation of the two-terminal oxyl-radical intermediate 3 through O-O cleavage. Compared with the nucleophilic attack of benzaldehyde by 2, the abstraction of a hydrogen atom from benzaldehyde by 3 requires higher energy. The nature of the nucleophilicity of 2 and 3 accounts for the reactivity of the reaction.

Mechanistic Investigation of Ni-Catalyzed Reductive Cross-Coupling of Alkenyl and Benzyl Electrophiles.

Mechanistic investigations of the Ni-catalyzed asymmetric reductive alkenylation of N-hydroxyphthalimide (NHP) esters and benzylic chlorides are reported. Investigations of the redox properties of the Ni-bis(oxazoline) catalyst, the reaction kinetics, and mode of electrophile activation show divergent mechanisms for these two related transformations. Notably, the mechanism of C(sp3) activation changes from a Ni-mediated process when benzyl chlorides and Mn0 are used to a reductant-mediated process that is gated by a Lewis acid when NHP esters and tetrakis(dimethylamino)ethylene is used. Kinetic experiments show that changing the identity of the Lewis acid can be used to tune the rate of NHP ester reduction. Spectroscopic studies support a NiII-alkenyl oxidative addition complex as the catalyst resting state. DFT calculations suggest an enantiodetermining radical capture step and elucidate the origin of enantioinduction for this Ni-BOX catalyst.

Computational Exploration of Dirhodium Complex-Catalyzed Selective Intermolecular Amination of Tertiary vs. Benzylic C-H Bonds.

The mechanism and origins of site-selectivity of Rh2(S-tfpttl)4-catalyzed C(sp3)-H bond aminations were studied using density functional theory (DFT) calculations. The synergistic combination of the dirhodium complex Rh2(S-tfpttl)4 with tert-butylphenol sulfamate TBPhsNH2 composes a pocket that can access both tertiary and benzylic C-H bonds. The nonactivated tertiary C-H bond was selectively aminated in the presence of an electronically activated benzylic C-H bond. Both singlet and triplet energy surfaces were investigated in this study. The computational results suggest that the triplet stepwise pathway is more favorable than the singlet concerted pathway. In the hydrogen atom abstraction by Rh-nitrene species, which is the rate- and site-selectivity-determining step, there is an attractive π-π stacking interaction between the phenyl group of the substrate and the phthalimido group of the ligand in the tertiary C-H activation transition structure. By contrast, such attractive interaction is absent in the benzylic C-H amination transition structure. Therefore, the DFT computational results clearly demonstrate how the synergistic combination of the dirhodium complex with sulfamate overrides the intrinsic preference for benzylic C-H amination to achieve the amination of the nonactivated tertiary C-H bond.

P/N-Heteroleptic Cu(I)-Photosensitizer-Catalyzed [3 + 2] Regiospecific Annulation of Aminocyclopropanes and Functionalized Alkynes.

We report here a regiospecific [3 + 2] annulation between aminocyclopropanes and various functionalized alkynes enabled by a P/N-heteroleptic Cu(I) photosensitizer under photoredox catalysis conditions. Thus, a divergent construction of 3-aminocyclopentene derivatives including methylsulfonyl-, arylsulfonyl-, chloro-, ester-, and trifluoromethyl-functionalized aminocyclopentenes could be achieved with advantages of high regioselectivity, broad substrate compatibility, and mild and environmentally benign reaction conditions.

Computational Studies on the Mechanism and Origin of the Different Regioselectivities of Manganese Porphyrin-Catalyzed C-H Bond Hydroxylation and Amidation of Equilenin Acetate.

The manganese porphyrin-catalyzed C-H bond hydroxylation and amidation of equilenin acetate developed by Breslow and his co-worker have been investigated with density functional theory (DFT) calculations. The hydroxylation of C(sp2)-H bond of equilenin acetate leading to the 6-hydroxylated product is more favorable than the hydroxylation of C(sp3)-H bond of equilenin acetate, leading to the 11ß-hydroxylation product. The computational results suggest that the C(sp2)-H bond hydroxylation of equilenin acetate undergoes an oxygen-atom-transfer mechanism, which is more favorable than the C(sp3)-H bond hydroxylation undergoing the hydrogen-atom-abstraction/oxygen-rebound (HAA/OR) mechanism by 1.6 kcal/mol. That is why, the 6-hydroxylated product is the major product and the 11ß-hydroxylated product is the minor product. In contrast, the 11ß-amidated product is the only observed product in manganese porphyrin-catalyzed amidation reaction. The benzylic amidation undergoes a hydrogen-atom-abstraction/nitrogen-rebound (HAA/NR) mechanism, in which hydrogen atom abstraction is followed by nitrogen rebound, leading to the 11ß-amidated product. The benzylic C(sp3)-H bond amidation at the C-11 position is more favorable than aromatic amidation at the C-6 position by 4.9 kcal/mol. Therefore, the DFT computational results are consistent with the experiments that manganese porphyrin-catalyzed C-H bond hydroxylation and amidation of equilenin acetate have different regioselectivities.

Understanding the structures and aromaticity of heteroporphyrins with computations.

Heteroporphyrins are porphyrin derivatives with replacement of the pyrrolic NH moiety by other heteroatom-containing groups, such as PH, AsH, SiH2, O, S, etc. For all studied heteroporphyrins, the macrocycle structure is distorted due to the presence of large heteroatoms. The HOMO-LUMO gap of heteroporphyrins is generally decreased compared to regular porphyrins. Both nucleus independent chemical shifts values and visualized anisotropy of induced current density were computed to describe the aromaticity of heteroporphyrins. The plots of anisotropy of induced current density suggest that the ring current diverged into an outer and an inner pathway at each ring. The current mainly passes through the outer path at the pyrrolic rings with inner hydrogen and through the inner path at the pyrrolic rings without inner hydrogen. In both regular porphyrin and O-substituted heteroporphyrins, the aromatic pathway is mainly contributed by the 22π-electron aromatic route model. Heteroatoms such as PH, AsH, S, Se and Te have little contribution to the aromaticity of heteroporphyrins. In addition, the π conjugation is also interrupted at the CH2 and SiH2 moiety, and the ring current mainly passes through the outer path of the heteroporphyrins with CH2 and SiH2 replacing the pyrrolic NH moiety. Therefore the 18π-[18]annulene model is dominated in PH-, AsH-, S-, Se-, Te-, CH2- and SiH2-substituted heteroporphyrins. These computational studies shed new light on the aromatic characters of heteroporphyrins, and will facilitate the further development of various novel heteroporphyrins.

Mechanism and stereoselectivity of benzylic C-H hydroxylation by Ru-porphyrin: a computational study.

The mechanism and origin of the stereoselectivity of asymmetric benzylic C-H hydroxylation by Ru-porphyrin were elucidated with density functional theory calculations. The reaction proceeds via a hydrogen-atom abstraction/oxygen-rebound pathway, wherein a high-valent ruthenium-oxo species abstracts a hydrogen atom from ethylbenzene to generate a radical pair intermediate, followed by the oxygen-rebound process to form 1-phenylethanol. The hydrogen-atom abstraction step is the rate- and stereoselectivity-determining step. Based on the mechanistic model, the computed stereoselectivity is in agreement with the experimental observations. Analysis of the distortion/interaction model suggests that stereoselectivity is determined by both the distortion energy of the ethylbenzene and the interaction energy between the ethylbenzene and the chiral Ru-porphyrin. The steric repulsion between the phenyl group of ethylbenzene and the bulky substituent of Ru-porphyrin is the leading cause of chiral induction.

Computational Exploration of Chiral Iron Porphyrin-Catalyzed Asymmetric Hydroxylation of Ethylbenzene Where Stereoselectivity Arises from π-π Stacking Interaction.

The mechanism and origins of stereoselectivity of chiral iron porphyrin-catalyzed asymmetric hydroxylation of ethylbenzene were explored with density functional theory. The hydrogen atom abstraction is the rate- and stereoselectivity-determining step. In good agreement with experimental results, the formation of the (R)-1-phenylethanol product is found to be the most favorable pathway. The transition state of hydrogen atom abstraction which leads to the (S)-1-phenylethanol product is unfavorable by 1.7 kcal/mol compared to the corresponding transition state which leads to the (R)-1-phenylethanol product. Enantioselectivity arises from an attractive π-π stacking interaction between the phenyl group of ethylbenzene substrate and the naphthyl group of the porphyrin ligand.

An ion synergism fluorescence probe via Cu2+ triggered competition interaction to detect glyphosate.

The widespread use of glyphosate (Gly) poses significant risks to environmental and human health, underscoring the urgent need for its sensitive and rapid detection. In this work, we innovated by developing a novel material, ionic liquids, which formed the ionic probe "[P66614]2[2,3-DHN]-Cu2+ (PDHN-Cu2+)" through coordination with Cu2+. This probe capitalized on the distinctive fluorescence quenching properties of ionic liquids in the presence of Cu2+, driven by synergistic interactions between anions and cations. Glyphosate disrupted the PDHN-Cu2+ coordination structure due to its stronger affinity for Cu2+, triggering a "turn-on" fluorescence response. Impressively, PDHN-Cu2+ enabled the sensitive detection of glyphosate within just one minute, achieving a detection limit as low as 71.4 nM and excellent recovery rates of 97-103% in diverse samples. This groundbreaking approach, utilizing ionic probes, lays a robust foundation for the accurate and real-time monitoring of pesticides, employing a strategy based on synergism and competitive coordination.

Cu(I)-Photosensitizer-Catalyzed Olefin-α-Amino Radical Metathesis/Demethylenative Cyclization of 1,7-Enynes.

A demethylenative En-Yne radical cyclization of 1,7-enynes has been successfully developed to chemoselectively afford 3,4-dihyroquinolin-2-ones or quinolin-2-ones under the catalysis of Cu(I) photosensitizers PS3 and PS6 with different redox potentials. The preliminary mechanistic experiments revealed that the reaction underwent an unprecedented olefin-α-amino radical metathesis-type process. A reasonable mechanism was proposed to illustrate the catalyst-controlled chemoselectivity of the reaction based on preliminary mechanistic experiments and DFT calculations.

Mechanistic Study of Chemoselectivity for Carbon Radical Hydroxylation versus Chlorination with FeIII (OH)(Cl) Complexes.

The FeIII (OH)(Cl) complex resembles the key intermediate proposed for the non-heme iron halogenases. Goldberg and co-workers reported that the FeIII (OH)(Cl) RC reacts with triphenylmethyl radical 1 to give an exclusive hydroxylation product. To understand the chemoselectivity of the reaction of RC with 1, density functional theory (DFT) calculations have been conducted. From RC, the competing pathways were identified as the OH-transfer, Cl-transfer, and isomerization pathways. The direct Cl-transfer is more favorable than direct OH-transfer by 2.8 kcal/mol. The hydrogen bonding interactions between the hydroxyl group and the pendent amine ligand impede the direct OH-transfer from RC. Compared with the direct Cl-transfer pathway, the isomerization pathways require lower barriers. In isomer RCiso2 , the equatorial hydroxyl group, which has smaller diabatic bond dissociation energy, prefers to transfer to form the hydroxylation product. In FeIII (Cl)2 RC2 and RC2iso , the equatorial chloride group also prefers to transfer to give the chlorination product.

Rh(iii)-catalyzed, hydrazine-directed C-H functionalization with 1-alkynylcyclobutanols: a new strategy for 1H-indazoles.

Rh(iii)-catalyzed coupling of phenylhydrazines with 1-alkynylcyclobutanols was realized through a hydrazine-directed C-H functionalization pathway. This [4+1] annulation, based on the cleavage of a Csp-Csp triple bond in alkynylcyclobutanol, provides a new pathway to prepare diverse 1H-indazoles under mild reaction conditions.