Mechanistic Investigation of Dirhodium-Catalyzed Intramolecular Allylic C–H Amination versus Alkene Aziridination

The reaction mechanisms and chemoselectivity on the intramolecular allylic C–H amination versus alkene aziridination of 4-pentenylsulfamate promoted by four elaborately selected dirhodium paddlewheel complexes are investigated by a DFT approach. A predominant singlet concerted, highly asynchronous pathway and an alternative triplet stepwise pathway are obtained in either C–H amination or alkene aziridination reactions when mediated by weak electron-donating catalysts. A singlet stepwise C–H amination pathway is obtained under strongly donating catalysts. The rate-determining step in the C–H amination is the H-abstraction process. The subsequent diradical-rebound C–N formation in the triplet pathway or the combination of the allylic carbocation and the negative changed N center in the singlet pathway require an identical energy barrier. A mixed singlet–triplet pathway is preferred in either the C–H insertion or alkene aziridination in the Rh₂(NCH₃CHO)₄ entry that the triplet pathway is initially favorable in the rate-determining steps, and the resultant triplet intermediates would convert to a singlet reaction coordinate. The nature of C–H amination or alkene aziridination is estimated to be a stepwise process. The theoretical observations presented in the paper are consistent with the experimental results and, more importantly, provide a thorough understanding of the nature of the reaction mechanisms and the minimum-energy crossing points

Fingerprint analysis and multi-component determination of Zibu Piyin recipe by HPLC with DAD and Q-TOF/MS method

<p>Zibu Piyin recipe (ZBPYR), a traditional Chinese medicine formula, is used for curing dementia caused by diabetes. For quality control of ZBPYR, fingerprint analysis and qualitative analysis using high-performance liquid chromatography (HPLC) with a diode-array detector, and confirmation using HPLC coupled with electrospray ionisation quadrupole time-of-flight tandem mass spectrometry (HPLC-Q-TOF-MS) were undertaken. HPLC fingerprint consisting of 34 common peaks was developed among 10 batches of ZBPYR, in which 7 common peaks were identified in comparison with the authentic standards and detected simultaneously. Furthermore, these seven compounds were verified by HPLC-Q-TOF-MS methods. The method can be applied to the quality control of ZBPYR.</p

Iron Phthalocyanine Decorated Nitrogen-Doped Graphene Biosensing Platform for Real-Time Detection of Nitric Oxide Released from Living Cells

Nitric oxide (NO) is a transcellular messenger involved in many physiological and pathological processes, but the real-time detection of NO in biological systems is still challenging due to its rapid diffusion, low concentration, and short half-life. A novel electrochemical sensing platform based on iron phthalocyanine (FePc) functionalized nitrogen-doped graphene (N-G) nanocomposites was constructed to achieve in situ monitoring of NO released from living cells on the sensing layer. By taking advantage of the synergetic effect of N-G and FePc nanocomposites, the N-G/FePc sensor displays excellent electrocatalytic activity toward NO with a high sensitivity of 0.21 μA μM^–1 cm^–2 and a low detection limit of 180 nmol L^–1. The following layer-by-layer assembly of poly-l-lysine (PLL) and Nafion further improved the capacity of resisting disturbance as well as the biocompatibility of the sensing interface. The flexible design of the ITO substrate based electrode provides a more controlled cellular biosensing system which could capture molecular signals immediately after NO released from human umbilical vein endothelial cells (HUVECs). The exhibited additional features of high sensitivity, rapid response, and ease of operation implies that the proposed N-G/FePc/Nafion/PLL ITO biosensor is a promising powerful platform in various complex biological systems

Multifunctional Paper Strip Based on Self-Assembled Interfacial Plasmonic Nanoparticle Arrays for Sensitive SERS Detection

A smart and multifunctional paper-based SERS sensing card is generated through patterning self-assembled interfacial arrays of gold nanoparticles (AuNPs) on the tip of an arrow-shaped paper strip. It is found that the closely packed monolayer of AuNPs is evenly distributed on the paper surface, resulting in a multitude of SERS hot spots over the detection zone. The paper card, with its inherent ability to separate and preconcentrate analytes by the capillary force and polarity difference between sample components, was exploited successfully as an integrated platform, allowing for sub-attomolar (50 × 10^–18 M) detection from microliter-volume (10 μL) samples. Furthermore, the simple preparation (lithography-free process), fast detection (<5 min), and low cost (<3 cents) demonstrate that the paper card is a practical and portable sensing interface for wide application in environmental and food analysis

Key Mechanistic Features of Ni-Catalyzed C–H/C–O Biaryl Coupling of Azoles and Naphthalen-2-yl Pivalates

The mechanism of the Ni-dcype-catalyzed C–H/C–O coupling of benzoxazole and naphthalen-2-yl pivalate was studied. Special attention was devoted to the base effect in the C–O oxidative addition and C–H activation steps as well as the C–H substrate effect in the C–H activation step. No base effect in the C­(aryl)–O oxidative addition to Ni-dcype was found, but the nature of the base and C–H substrate plays a crucial role in the following C–H activation. In the absence of base, the azole C–H activation initiated by the C–O oxidative addition product Ni­(dcype)­(Naph)­(PivO), <b>1B</b>, proceeds via Δ<i>G</i> = 34.7 kcal/mol barrier. Addition of Cs₂CO₃ base to the reaction mixture forms the Ni­(dcype)­(Naph)­[PivOCs·CsCO₃], <b>3_Cs_clus</b>, cluster complex rather than undergoing PivO^– → CsCO₃^– ligand exchange. Coordination of azole to the resulting <b>3_Cs_clus</b> complex forms intermediate with a weak Cs–heteroatom­(azole) bond, the existence of which increases acidity of the activated C–H bond and reduces C–H activation barrier. This conclusion from computation is consistent with experiments showing that the addition of Cs₂CO₃ to the reaction mixture of <b>1B</b> and benzoxazole increases yield of C–H/C–O coupling from 32% to 67% and makes the reaction faster by 3-fold. This emerging mechanistic knowledge was validated by further exploring base and C–H substrate effects via replacing Cs₂CO₃ with K₂CO₃ and benzoxazole (<b>1a</b>) with 1<i>H</i>-benzo­[<i>d</i>]­imidazole (<b>1b</b>) or quinazoline (<b>1c</b>). We proposed the modified catalytic cycle for the Ni­(cod)­(dcype)-catalyzed C–H/C–O coupling of benzoxazole and naphthalen-2-yl pivalate

Mechanistic Details of Pd(II)-Catalyzed C–H Iodination with Molecular I₂: Oxidative Addition vs Electrophilic Cleavage

Transition metal-catalyzed C–H bond halogenation is an important alternative to the highly utilized directed-lithiation methods and increases the accessibility of the synthetically valuable aryl halide compounds. However, this approach often requires impractical reagents, such as IOAc, or strong co-oxidants. Therefore, the development of methodology utilizing inexpensive oxidants and catalyst containing earth-abundant transition metals under mild experimental conditions would represent a significant advance in the field. Success in this endeavor requires a full understanding of the mechanisms and reactivity governing principles of this process. Here, we report intimate mechanistic details of the Pd­(II)-catalyzed C–H iodination with molecular I₂ as the sole oxidant. Namely, we elucidate the impact of the: (a) Pd-directing group (DG) interaction, (b) nature of oxidant, and (c) nature of the functionalized C–H bond [C­(sp²)–H vs C­(sp³)–H] on the Pd­(II)/Pd­(IV) redox and Pd­(II)/Pd­(II) redox-neutral mechanisms of this reaction. We find that both monomeric and dimeric Pd­(II) species may act as an active catalyst during the reaction, which preferentially proceeds via the Pd­(II)/Pd­(II) redox-neutral electrophilic cleavage (EC) pathway for all studied substrates with a functionalized C­(sp²)–H bond. In general, a strong Pd–DG interaction increases the EC iodination barrier and reduces the I–I oxidative addition (OA) barrier. However, the increase in Pd–DG interaction alone is not enough to make the mechanistic switch from EC to OA: This occurs only upon changing to substrates with a functionalized C­(sp³)–H bond. We also investigated the impact of the nature of the electrophile on the C­(sp²)–H bond halogenation. We predicted molecular bromine (Br₂) to be more effective electrophile for the C­(sp²)–H halogenation than I₂. Subsequent experiments on the stoichiometric C­(sp²)–H bromination by Pd­(OAc)₂ and Br₂ confirmed this prediction.The findings of this study advance our ability to design more efficient reactions with inexpensive oxidants under mild experimental conditions

Platinum(II)-Catalyzed Cyclization Sequence of Aryl Alkynes via C(sp³)–H Activation: A DFT Study

The mechanism and intermediates of hydroalkylation of aryl alkynes via C­(sp³)–H activation through a platinum­(II)-centered catalyst are investigated with density functional theory at the B3LYP/[6-31G­(d) for H, O, C; 6-31+G­(d,p) for F, Cl; SDD for Pt] level of theory. Solvent effects on reactions were explored using calculations that included a polarizable continuum model for the solvent (THF). Free energy diagrams for three suggested mechanisms were computed: (a) one that leads to formation of a Pt­(II) vinyl carbenoid (Mechanism A), (b) another where the transition state implies a directed 1,4-hydrogen shift (Mechanism B), and (c) one with a Pt-aided 1,4-hydrogen migration (Mechanism C). Results suggest that the insertion reaction pathway of Mechanism A is reasonable. Through 4,5-hydrogen transfer, the Pt­(II) vinyl carbenoid is formed. Thus, the stepwise insertion mechanism is favored while the electrocyclization mechanism is implausible. Electron-withdrawing/electron-donating groups substituted at the phenyl and benzyl sp³ C atoms slightly change the thermodynamic properties of the first half of Mechanism A, but electronic effects cause a substantial shift in relative energies for the second half of Mechanism A. The rate-limiting step can be varied between the 4,5-hydrogen shift process and the 1,5-hydrogen shift step by altering electron-withdrawing/electron-donating groups on the benzyl C atom. Additionally, NBO and AIM analyses are applied to further investigate electronic structure changes during the mechanism

Mechanism and Enantioselectivity of Dirhodium-Catalyzed Intramolecular C–H Amination of Sulfamate

The mechanisms and enantioselectivities of the dirhodium (Rh₂L₄, L = formate, <i>N</i>-methylformamide, <i>S</i>-nap)-catalyzed intramolecular C–H aminations of 3-phenylpropylsulfamate ester have been investigated in detail with BPW91 density functional theory computations. The reactions catalyzed by the Rh₂^II,II catalysts start from the oxidation of the Rh₂^II,II dimer to a triplet mixed-valent Rh₂^II,III–nitrene radical, which should facilitate radical H-atom abstraction. However, in the Rh₂(formate)₄-promoted reaction, as a result of a minimum-energy crossing point (MECP) between the singlet and triplet profiles, a direct C–H bond insertion is postulated. The Rh₂(<i>N</i>-methylformamide)₄ reaction exhibits quite different mechanistic characteristics, taking place via a two-step process involving (i) intramolecular H-abstraction on the triplet profile to generate a diradical intermediate and (ii) C–N formation by intersystem crossing from the triplet state to the open-shell singlet state. The stepwise mechanism was found to hold also in the reaction of 3-phenylpropylsulfamate ester catalyzed by Rh₂(<i>S</i>-nap)_4. Furthermore, the diradical intermediate also constitutes the starting point for competition steps involving enantioselectivity, which is determined by the C–N formation open-shell singlet transition state. This mechanistic proposal is supported by the calculated enantiomeric excess (94.2% <i>ee</i>) with the absolute stereochemistry of the product as <i>R</i>, in good agreement with the experimental results (92.0% <i>ee</i>)