Donghui Wei

Cobalt(II)-Catalyzed C-H Amination of Arenes with Simple Alkylamines.

A new method of cobalt-catalyzed amination of arylamides with simple alkylamines is reported through C(sp(2))-H bond functionalization. For the first time, inexpensive cobalt is exploited as the catalyst in the amination of C(sp(2))-H bond using simple alkylamines.

A quantum mechanical study of the mechanism and stereoselectivity of the N-heterocyclic carbene catalyzed [4 + 2] annulation reaction of enals with azodicarboxylates

A systematic theoretical study has been carried out to understand the mechanism and stereoselectivity of [4 + 2] annulation reaction between γ-oxidized enals and azodicarboxylates catalyzed by the N-heterocyclic carbene (NHC). The calculated results reveal that the catalytic cycle can be characterized by three stages (Stages 1, 2, and 3). Stage 1 is the nucleophilic addition of the NHC catalyst to enals upon the intramolecular proton transfer to generate the Breslow intermediate. In this stage, apart from the direct proton transfer mechanism, the H2O (H2O and 2H2O cluster) and bicarbonate anion (HCO3−) mediated proton transfer mechanisms are also investigated; the free energy barrier for the crucial proton transfer steps in Stage 1 is found to be significantly lower by explicit inclusion of the bicarbonate anion (HCO3−). For Stage 2, the removal of the leaving group occurs, followed by C–C bond rotation for the formation of cis-dienolate. Stage 3 is the endo/exo [4 + 2] cycloaddition and dissociation of the catalyst from the final products. The formal [4 + 2] cycloaddition step is calculated to be the enantioselectivity determining step, and the R-configured PR is the predominant product according to the computations, which is in good agreement with the experimental observations. Moreover, the stereoselectivity associated with the chiral carbon center is attributed to the CH–π interaction between Cα−H and the mesityl group of NHC and the variation in the distortion of the dienolate. The mechanistic insights obtained in the present study should be valuable for the other NHC-catalyzed reactions.

Peroxides as "Switches" of Dialkyl H‑Phosphonate: Two Mild and Metal-Free Methods for Preparation of 2‑Acylbenzothiazoles and Dialkyl Benzothiazol-2-ylphosphonates

Two mild and metal-free methods for the preparation of two kinds of important benzothiazole derivatives, 2-acylbenzothiazoles and dialkyl benzothiazol-2-ylphosphonates, respectively, were developed. The dialkyl H-phosphonate (RO)2P(O)H exists in equilibrium with its tautomer dialkyl phosphite (RO)2POH. TBHP triggered α-carbon-centered phosphite radical formation, whereas DTBP triggered phosphorus-centered phosphonate radical formation. The two types of radicals led respectively to two different reaction processes, the direct C2-acylation of benzothiazoles and C2-phosphonation of benzothiazoles.

DFT study on the mechanisms and stereoselectivities of the [4 + 2] cycloadditions of enals and chalcones catalyzed by N-heterocyclic carbene.

The possible reaction mechanisms of stereoselective [4 + 2] cycloaddition of enals and chalcones catalyzed by N-heterocyclic carbene (NHC) have been investigated using density functional theory (DFT). The calculated results indicate that the most favorable reaction channel occurs through five steps. The first step is the nucleophilic attack on the enal by NHC. Then, there are two consecutive acid (AcOH)-assisted proton-transfer steps. Subsequently, the fourth step is the [4 + 2] cycloaddition process associated with the formation of two chiral centers, followed by dissociation of NHC and product. Our computational results demonstrate that the [4 + 2] cycloaddition is the rate-determining and stereoselectivity-determining step. The energy barrier for the SS configurational channel (17.62 kcal/mol) is the lowest one, indicating the SS configurational product should be the main product, which is in agreement with experiment. Moreover, the role of NHC catalyst in the [4 + 2] cycloaddition of enal and chalcone was explored by the analysis of global reactivity indexes. This work should be helpful for realizing the significant roles of catalyst NHC and the additive AcOH and thus provide valuable insights on the rational design of potential catalyst for this kind of reactions.

DFT Study on the Mechanisms and Diastereoselectivities of Lewis Acid-Promoted Ketene–Alkene [2 + 2] Cycloadditions: What is the Role of Lewis Acid in the Ketene and C = X (X = O, CH2, and NH) [2 + 2] Cycloaddition Reactions?

The detailed mechanisms and diastereoselectivities of Lewis acid-promoted ketene-alkene [2 + 2] cycloaddition reactions have been studied by density functional theory (DFT). Four possible reaction channels, including two noncatalyzed diastereomeric reaction channels (channels A and B) and two Lewis acid (LA) ethylaluminum dichloride (EtAlCl2) catalyzed diastereomeric reaction channels (channels C and D), have been investigated in this work. The calculated results indicate that channel A (associated with product R-configurational cycloputanone) is more energy favorable than channel B (associated with the other product S-configurational cyclobutanone) under noncatalyzed condition, but channel D leading to S-configurational cyclobutanone is more energy-favorable than channel C, leading to R-configurational cycloputanone under a LA-promoted condition, which is consistent with the experimental results. And Lewis acid can make the energy barrier of ketene-alkene [2 + 2] cycloaddition much lower. In order to explore the role of LA in ketene and C = X (X = O, CH2, and NH) [2 + 2] cycloadditions, we have tracked and compared the interaction modes of frontier molecular orbitals (FMOs) along the intrinsic reaction coordinate (IRC) under the two different conditions. Besides by reducing the energy gap between the FMOs of the reactants, our computational results demonstrate that Lewis acid lowers the energy barrier of the ketene and C = X [2 + 2] cycloadditions by changing the overlap modes of the FMOs, which is remarkably different from the traditional FMO theory. Furthermore, analysis of global reactivity indexes has also been performed to explain the role of LA catalyst in the ketene-alkene [2 + 2] cycloaddition reaction.

DFT perspective toward [3 + 2] annulation reaction of enals with α-ketoamides through NHC and Brønsted acid cooperative catalysis: mechanism, stereoselectivity, and role of NHC

A systematic theoretical study has been carried out to understand the possible mechanisms and stereoselectivity of the N-heterocyclic carbene (NHC)-catalyzed [3 + 2] annulation reaction of enals with α-ketoamides using density functional theory (DFT) calculations. The calculated results reveal that the favorable pathway comprises of seven steps, i.e., addition of the catalyst, formation of the Breslow intermediate, formation of the enolate intermediate, the C–C bond formation step, the proton transfer process, the ring-closure process and the regeneration of the catalyst. For the proton transfer process, apart from the direct proton transfer mechanism, the base TMEDA and the in situ generated Bronsted acid TMEDA·H+ mediated proton transfer mechanisms are also investigated; the free energy for the crucial proton transfer steps is found to be significantly lowered by explicit inclusion of the Bronsted acid TMEDA·H+. The computational results show that the C–C bond formation step is the stereoselectivity-determining step, in which two chirality centers assigned to the coupling carbon atoms are formed, and the RR-configured diastereomer is the predominant product, which is in good agreement with the experimental observations. Global reaction index (GRI) analysis has been performed to confirm that NHC mainly plays a role of a Lewis base catalyst. In addition, the distortion/interaction, NCI, and NBO analyses show that the strong interaction and electron delocalization of the reaction active site determine the stereoselectivity, with the RR-configured product being generated preferentially. The mechanistic insights obtained in the present study should be valuable for the rational design of an effective organocatalyst for this kind of reaction with high stereoselectivity.

Insights into Stereoselective Aminomethylation Reaction of α,β-Unsaturated Aldehyde with N,O-Acetal via N-Heterocyclic Carbene and Brønsted Acid/Base Cooperative Organocatalysis

A theoretical investigation has been performed to interrogate the mechanism and stereoselectivities of aminomethylation reaction of α,β-unsaturated aldehyde with N,O-acetal, which is initiated by N-heterocyclic carbene and Brønsted acid (BA). The calculated results disclose that the reaction contains several steps, i.e., formation of the actual catalysts NHC and Brønsted acid Et3N·H(+) coupled with activation of C-O bond of N,O-acetal, nucleophilic attack of NHC on α,β-unsaturated aldehyde, formation of Breslow intermediate, β-protonation for the formation of enolate intermediate, nucleophilic addition on the Re/Si face to enolate by the activated iminium cation, esterification coupled with regeneration of Et3N·H(+), and dissociation of NHC from product. Addition on the prochiral face of enolate should be the stereocontrolling step, in which the chiral α-carbon is formed. Furthermore, NBO, GRI, and FMO analyses have been performed to explore the roles of catalysts and origin of stereoselectivity. Surprisingly, the added Brønsted base (BB) Et3N plays an indispensable role in the esterification process, indicating the reaction proceeds under NHC-BA/BB multicatalysis rather than NHC-BA dual catalysis proposed in the experiment. This theoretical work provides a case on the exploration of the special roles of the multicatalysts in NHC chemistry, which is valuable for rational design on new cooperative organocatalysis.

Insights into the Unexpected Chemoselectivity for the N-Heterocyclic Carbene-Catalyzed Annulation Reaction of Allenals with Chalcones.

Lewis base N-heterocyclic carbene (NHC)-catalyzed annulation is the subject of extensive interest in synthetic chemistry, but the reaction mechanisms, especially the unexpected chemoselectivity of some of these reactions, are poorly understood. In this work, a systematic theoretical calculation has been performed on NHC-catalyzed annulation between allenals and chalcone. Multiple possible reaction pathways (A-E) leading to three different products have been characterized. The calculated results reveal that NHC is more likely to initiate the reaction by nucleophilic attack on the center carbon atom of the allene group but not the carbonyl carbon atom in allenals leading to the Breslow intermediate, which is remarkably different from the other NHC-catalyzed annulations of unsaturated aldehydes with chalcones. The computed energy profiles demonstrate that the most energetically favorable pathway (A) results in polysubstituted pyranyl aldehydes, which reasonably explains the observed chemoselectivity in the experiment. The observed chemoselectivity is demonstrated to be thermodynamically but not kinetically controlled, and the stability of the Breslow intermediate is the key for the possibility of homoenolate pathway D and enolate pathway E. This work can improve our understanding of the multiple competing pathways for NHC-catalyzed annulation reactions of unsaturated aldehydes with chalcones and provide valuable insights for predicting the chemoselectivity for this kind of reaction.

DFT investigation on mechanisms and stereoselectivities of [2 + 2 + 2] multimolecular cycloaddition of ketenes and carbon disulfide catalyzed by N-heterocyclic carbenes.

The first theoretical investigation using density functional theory (DFT) methods to study the detailed reaction mechanisms of stereoselective [2 + 2 + 2] multimolecular cycloaddition of ketene (two molecules) and carbon disulfide (CS2, one molecule) which is catalyzed by N-heterocyclic carbene (NHC) is presented in this paper. The calculated results indicate that this reaction occurs through four steps: the complexation of NHC with ketene (channel 1a) rather than with CS2 (channel 1b), addition of CS2 (channel 2b) but not dimerization of ketene (channel 2a), formal [4 + 2] cycloaddition with a second molecule of ketene (channel 3a) rather than intramolecular [2 + 2] cycloaddition (channel 3b), and finally regeneration of NHC. The second step is revealed to be the rate-determining step. Moreover, the stereoselectivities associated with the chiral carbon center and the carbon double bond are predicted to be respectively determined in the second and third steps and respectively R and E configurations dominated, which are in good agreement with the experimental results. Furthermore, the possible mechanisms of the identical [2 + 2 + 2] cycloaddition catalyzed by N,N-dimethylpyridin-4-amine (DMAP) have also been investigated to help understand the ring closure mechanism proceeding in the third step.

Mechanisms of the cascade synthesis of substituted 4‐amino‐1,2,4‐triazol‐3‐one from huisgen zwitterion and aldehyde hydrazone: A DFT study

The detailed reaction mechanisms of the title reaction are shed light on by using the density functional theory (DFT). The calculated results have demonstrated that the whole reaction takes place via four processes (processes (I–IV)), among which, three possible reaction mechanisms are proposed for process (II) (channels 1–3) and two for process (IV) (channels 4–5). According to our calculated results, channel 3 and channel 5 are verified to be most energetically favorable. As interpreted in the text, in process (II), the proton transfer should be performed prior to the nucleophilic attack, and the AA‐Type transfer strategy is more likely to occur. The global reactivity index (GRI) and frontier molecular orbital (FMO) analyses of the aldehyde hydrazone have further supported the AA‐Type mechanism. In process (IV), however, the titled product has been demonstrated to be formed by the synergetic elimination of two protons via a six‐membered ring transition state. Taking an integrated view, the highest energy barrier for the whole reaction along the most favorable pathway is 32.19 kcal/mol, which is consistent with the mild thermal experimental conditions. More interestingly, the qualified mechanisms in this work have given a perfect explanation to the optimal reactants molar ratio of highest yields (R1/R2/R3 = 2/1/1) employed in the experiment.