Lu Jin

Theoretical Insight into the Mechanism of Gold(I)-Catalyzed Rearrangement of 2-Propargyl 2H-Azirines to Pyridines

The title reaction is investigated in detail theoretically using density functional theory. After 5-endo-dig cyclization by nucleophilic attack, five possible pathways are taken into account in this work: direct ring expansion followed or accompanied by proton-transfer (paths A and B, respectively), 1,3-cationic migration (path C), proton-transfer before ring expansion (path D), and processing via a gold-nitrene (path E). Results indicate that the reaction would undergo the favored sequential pathway (path A) rather than other pathways. Moreover, the concerted mechanism (path B), which is designed to account for the selectivity of product in the experiment, would be unlikely in the reaction. The selectivity of product could be explained by the hindrance of ligand (t-BuXPhos) and the stability of the carbocation. Moreover, the binding energy of product complexes could account for the observed reaction rate.

Computational Study on the Aminolysis of β-Hydroxy-α,β-Unsaturated Ester via the Favorable Path Including the Formation of α-Oxo Ketene Intermediate

The possible mechanisms of the aminolysis of N-methyl-3-(methoxycarbonyl)-4-hydroxy-2-pyridone (beta-hydroxy-alpha,beta-unsaturated ester) with dimethylamine are investigated at the hybrid density functional theory B3LYP/6-31G(d,p) level in the gas phase. Single-point computations at the B3LYP/6-311++G(d,p) and the Becke88-Becke95 1-parameter model BB1K/6-311++G(d,p) levels are performed for more precise energy predictions. Solvent effects are also assessed by single-point calculations at the integral equation formalism polarized continuum model IEFPCM-B3LYP/6-311++G(d,p) and IEFPCM-BB1K/6-311++G(d,p) levels on the gas-phase optimized geometries. Three possible pathways, the concerted pathway (path A), the stepwise pathway involving tetrahedral intermediates (path B), and the stepwise pathway via alpha-oxo ketene intermediate due to the participation of beta-hydroxy (path C), are taken into account for the title reaction. Moreover, path C includes two sequential processes. The first process is to generate alpha-oxo ketene intermediate via the decomposition of N-methyl-3-(methoxycarbonyl)-4-hydroxy-2-pyridone; the second process is the addition of dimethylamine to alpha-oxo ketene intermediate. Our results indicate that path C is more favorable than paths A and B both in the gas phase and in solvent (heptane). In path C, the first process is the rate-determining step, and the second process is revealed to be a [4+2] pseudopericyclic reaction without the energy barrier. Being independent of the concentration of amine, the first process obeys the first-order rate law.

Theoretical study on the hydrolysis mechanism of N,N-dimethyl-N′-(2-oxo-1, 2-dihydro-pyrimidinyl)formamidine: Water-assisted mechanism and cluster-continuum model

The hydrolysis reaction of N,N‐dimethyl‐N′‐(2‐oxo‐1, 2‐dihydro‐pyrimidinyl)formamidine (DMPFA), a model compound of the antivirus drug amidine‐3TC (3TC = 2′, 3′‐dideoxy‐3′‐thiacytidine), is investigated by the hybrid density functional theory B3LYP/6‐31+G (d,p) method. The hydrolysis reaction of the title compound is predicted to undergo via two pathways, each of which is a stepwise process. Path A is the addition of H2O to the CN double bond in the amidine group to form a tetrahedral structure in its first step, and then the transfer of the H atom of hydroxyl leads to the corresponding products via four possible channels. Path B simultaneously involves the nucleophilic attack of H2O to the C atom of the CN bond and the proton transfer to the N atom of amino group leading to the cleavage of the CN single bond in the amidine group. The results indicate that path A is more favorable than path B in the gas phase. Moreover, to simulate the title reaction in aqueous solution, water‐assisted mechanism and the cluster‐continuum model, based on the SCRF/CPCM model, are taken into account in our work. The results indicate that it is rational for two water molecules served as a bridge to assist in the first step of path A and that cytosine rather than the cytosine‐substituted formamide should be released from the tetrahedral intermediate via s six‐membered cycle transition state (channel 2). Our calculations exhibit that the process toward the tetrahedral intermediate is the rate‐determining step both in the gas phase and in aqueous solution.

Mechanisms of norbornadiene dimerization to Binor-S using cationic Co(I), Rh(I), and Ir(I) catalysts.

We investigated the transition metal‐catalyzed reaction mechanisms of NBD dimerization to Binor‐S using cationic CoI, RhI, and IrI catalysts, using mPW1PW91, mPW1K, and B3LYP density functional methods. Our results indicate that the monomeric metal center has the ability to bind with four double bonds of two NBD molecules with a syn spatial geometry to form a penta‐coordinated complex. We designed three possible pathways, but found two of them blocked. The favored pathway involves three steps from the reactant precursor to the product precursor: the first step is the formation of a single bond to connect two NBD units, the second is the alkene insertion leading to the formation of the three‐membered ring structure, and the final step is the formation of the final product precursor. Orbital analysis showed metal…CC σ agostic interaction in the product precursor, which is in agreement with the previous experimental findings. In addition, we found that the solvent and counter‐ions had significant effects on the dimerization reactions.

Mechanistic investigation on radical-induced construction of oxindoles: radical versus electrophilic cyclization

This work is based on our previous reported experimental results (RSC Advances, 2016, 6, 27000). The mechanism of constructing oxindoles via tandem radical reaction of N-arylacrylamide with tertiary cycloalkanols is theoretically explored by using density functional theory (DFT). A four-step mechanism was put forward for the reaction. Step 1 is related with the ring-opening process of cycloalkanol radical after the oxidation, step 2 corresponds to the intermolecular attack between keto-included alkyl radical and N-methyl-N-phenylmethacrylamide, step 3 is associated with the intramolecular C–C bond formation via the cationic attack, and step 4 is the deprotonation towards the final product. It is found that step 2 is the rate-limiting step. Importantly, step 3 is updated to be a cationic step (channel 2), instead of the previously suggested radical step (channel 1). After the ring-opening processes, comparative study indicates that the intramolecular reactions of β-, γ-, and δ-keto radicals determines the product selectivity. The low selectivity of product in the cyclopentanol-involved reaction would originate from the high competition between intra- and intermolecular reactions, which is in agreement with our previous experimental observations.

Theoretical insight into the Au(I)-catalyzed hydration of halo-substituted propargyl acetate: dynamic water-assisted mechanism

The hydration mechanism of halo-substituted propargyl acetate, catalyzed by a homogenous Au(I) complex, has been investigated with the aid of the density functional theory (DFT) method. Our results reveal that the hydration is initiated by the favoured 1,5-exo-dig cycloaddition in the anti manner, affording a desired regioselective Markovnikov product. We also verify that neither the pathway towards the anti-Markovnikov product triggered by 1,6-endo-dig cycloaddition, nor direct nucleophilic attack by water, would happen without the help of neighbouring carbonyl groups. The favoured pathway mainly includes three processes: nucleophilic attack after 1,5-exo-dig cycloaddition, protodeauration, and enol–keto tautomerization. It turns out that the third process (enol–keto tautomerization) is the rate-determining step. Additionally, different halo-substituents cannot change the reaction trend, but slightly affect the relative energies. Particularly, cluster-continuum solvent models were established for some proton-transfer steps to rationally simulate reaction processes and evaluate energy barriers. Our study suggests that the presence of an explicit water-bridge is crucial to promote the hydration reaction. Computational results provide theoretical support for experimental observations, and insight into the hydration.