A computational study with the Becke3LYP density functional was carried out to elucidate the mechanisms of Au(I)-catalyzed reactions of enynyl acetates involving tandem [3,3]-rearrangement, Nazarov reaction, and [1,2]-hydrogen shift. Calculations indicate that the [3,3]-rearrangement is a two-step process with activation free energies below 10 kcal/mol for both steps. The following Nazarov-type 4pi electrocyclic ring-closure reaction of a Au-containing dienyl cation is also easy with an activation free energy of 3.2 kcal/mol in CH2Cl2. The final step in the catalytic cycle is a [1,2]-hydride shift, and this step is the rate-limiting step (with a computed activation free energy of 20.2 kcal/mol) when dry CH2Cl2 is used as the solvent. When this tandem reaction was conducted in wet CH2Cl2, the [1,2]-hydride shift step in dry solution turned to a very efficient water-catalyzed [1,2]-hydrogen shift mechanism with an activation free energy of 16.4 kcal/mol. Because of this, the tandem reaction of enynyl acetates was found to be faster in wet CH2Cl2 as compared to the reaction in dry CH2Cl2. Calculations show that a water-catalyzed [1,2]-hydrogen shift adopts a proton-transport catalysis strategy, in which the acetoxy group in the substrate is critical because it acts as either a proton acceptor when one water molecule is involved in catalysis or a proton-relay stabilizer when a water cluster is involved in catalysis. Water is found to act as a proton shuttle in the proton-transport catalysis strategy. Theoretical discovery of the role of the acetoxy group in the water-catalyzed [1,2]-hydrogen shift process suggests that a transition metal-catalyzed reaction involving a similar hydrogen shift step can be accelerated in water or on water with only a marginal effect, unless a proton-accepting group such as an acetoxy group, which can form a hydrogen bond network with water, is present around this reaction's active site.

The results of an experimental and ONIOM-based computational investigation of the mechanism and the origins of enantioselectivity in the asymmetric synthesis of alpha-amino phosphonates by an enantioselective hydrophosphonylation of imines catalyzed by chiral Brønsted acids are reported. It was found that the enantioselectivity observed in the enantioselective hydrophosphonylation of the imine with a benzothiazole moiety was poor. A detailed computational study with a two-layer ONIOM (B3LYP/6-31G(d)/AM1) method on the mechanism of the investigated reaction was carried out to explore the origins of the enantioselectivity. Calculations indicate that the investigated reaction is a two-step process involving proton-transfer and nucleophilic addition, which is the stereo-controlling step. The investigated reaction prefers a di-coordination pathway to a mono-coordination pathway. The different enantioselectivities exhibited by three kinds of catalyst and two kinds of nucleophile were rationalized. Calculations indicate that si-facial attack is higher in energy than re-facial attack by only 0.1 kcal/mol, which accounts well for the low ee value observed in the enantioselective hydrophosphonylation of the imine with a benzothiazole moiety. The energy barrier for phosphonate-phosphite tautomerism catalyzed by chiral Brønsted acid in toluene is only 1.8 kcal/mol, which could explain why the investigated reaction can take place at room temperature.

3-(1-Arylsulfonylalkyl)indoles as electrophiles in the N-heterocyclic carbene-catalyzed umpolung reaction of aldehydes were realized for the first time. This intermolecular Stetter-type reaction features the commercially available catalyst and mild reaction conditions, providing alpha-(3-indolyl) ketone derivatives in high yields for a wide range of substrates.

A regiospecific strategy for the preparation of N(7)-substituted purines in an efficient manner was devised. This approach to 6,7,8-trisubstituted purines relies on the cyclization reactions of suitably substituted pyrimidines (1) with either a carboxylic acid or an aldehyde. The method development for the five-step synthetic strategy outlined here was completed using 5-amino-4,6-dichloropyrimidine (4) as the starting material. The utility of this methodology was demonstrated through the preparation of a 40-membered library of 6,7,8-trisubstituted purines (3) in good yields and high purity.

Aminocyclopentadienyl ruthenium hydride complexes were optimized at the second-order Møller−Plesset (MP2) level of theory with 6-31G(d) and 6-311++G(d,p) basis sets to investigate the nature of intramolecular interactions. The computations show that both Ru−H···H−N dihydrogen bond interactions and Ru···H−N interactions are responsible for the stability of these complexes. The BSSE-corrected interaction energies, computed at the B3LYP and MP2 levels of theory with 6-31G(d), 6-311++G(d,p), and 6-311++G(2d,2p) basis sets, indicate that the dihydrogen bond interaction energy accounts for only 20% of the total interaction energy. Therefore, the Ru···H−N interactions play a key role in stabilizing the aminocyclopentadienyl ruthenium hydride complexes. Topological analysis of electron density at bond critical points confirms the formation of the dihydrogen bonds between oppositely charged hydrogen atoms. Analysis of charge distributions (Mulliken charges) shows there is a strong electronic attraction between Ru and the hydrogen atom.

No abstract

Nitrones have been used for rhodium-catalyzed cyclization C-H bond activation and O atom transfer of arylnitrones with alkynes by Chang et al. ( J. Am. Chem. Soc. 2015 , 137 , 4908 - 4911 ). Density functional theory method has been used to study the mechanism, regio-, and diastereoselectivity of type reactions. The results elucidated that the reaction pathway for Rh(III)-catalyzed cyclization of N-arylnitrones with alkyne contains a C-H bond activation, an alkyne insertion into Rh-C bond, a reductive elimination to form a Rh(I) complex, an oxidative addition leading to N-O cleavage, an imine insertion into the Rh-C bond, and the final protonolysis to regenerate the products and the active catalyst. The regioselectivity of this reaction with asymmetric alkyne is controlled by the electronic effect in alkyne insertion type instead of steric effects. The distortion-interaction analysis is also used to explain the regioselectivity. The diastereoselectivity is controlled by the imine insertion step. In this step, the sterically less hindered transition state is favored, leading to stereoselective product formation.

The mechanism of Rh-catalyzed decarboxylative conjugate addition has been investigated with Density Functional Theory (DFT). Calculations indicate that the selectivity toward hydrolysis or β-hydride elimination of the investigated reaction is a compromise between diffusion control and kinetic control. Ligand control can be adjusted by modifying the intermolecular interaction between the Rh(I) enolate intermediate and water.