Theoretical Investigations toward the Asymmetric Insertion Reaction of Diazoester with Aldehyde Catalyzed by N-Protonated Chiral Oxazaborolidine: Mechanisms and Stereoselectivity

Abstract

In recent years, the N-protonated chiral oxazaborolidine has been utilized as the Lewis acid catalyst for the asymmetric insertion reaction, which is one of the most challenging topics in current organic chemistry. Nevertheless, the reaction mechanism, stereoselectivity, and regioselectivity of this novel insertion reaction are still unsettled to date. In this present work, the density functional theory (DFT) investigation has been performed to interrogate the mechanisms and stereoselectivities of the formal C-C/H insertion reaction between benzaldehyde and methyl α-benzyl diazoester catalyzed by the N-protonated chiral oxazaborolidine. For the reaction channel to produce the R-configured C-C insertion product as the predominant isomer, the catalytic cycle can be characterized by four steps: (i) the complexation of the aldehyde with catalyst, (ii) addition of the other reactant methyl α-benzyl diazoester, (iii) the removal of nitrogen concerted with the migration of phenyl group or hydrogen, and (iv) the dissociation of catalyst from the products. Our computational results show that the carbon-carbon bond formation step is the stereoselectivity determining step, and the reaction pathways associated with [1, 2]-phenyl group migration occur preferentially to those pathways associated with [1, 2]-hydrogen migration. The pathway leading to the R-configured product is the most favorable pathway among the possible stereoselective pathways. All these calculated outcomes align well with the experimental observations. The novel mechanistic insights should be valuable for understanding this kind of reaction.

DFT Study on the Mechanism and Stereoselectivity of NHC-Catalyzed Synthesis of Substituted Trifluoromethyl Dihydropyranones with Contiguous Stereocenters

“…Following a typical 1,2-H shift process, a highly strained three-membered ring structure would present in the transition state of this direct proton transfer (DPT) pathway, which will probably induce a highly unreasonable reaction energy barrier. Then, inspired by previous investigations conducted by our own and other’s groups, − we proposed another two possible pathways: the bimolecular proton transfer (BPT) pathway with assistance of another molecule of α-aroyloxyaldehyde R1 and the bicarbonate anion-assisted proton transfer (BAAPT) pathway with HCO 3 – , which is the byproduct of the reaction of Pre-Cat with the base Cs 2 CO 3 (Scheme ) acting as the medium. The transition states for the DPT, BPT, and BAAPT pathways are denoted as TS2 , TS3 , and TS4 , respectively.…”

Me3SiBr/InCl3 catalyzed allylation of alcohols: Identifying the combined Lewis structure and investigating the reaction mechanism

“…Gaussian09 was employed for all the calculations. DFT is the most powerful method for understanding the compound structures and reaction mechanism . All the geometries including reactants, intermediates, transition states, and products were obtained at ωB97XD/def2‐SVP theory level .…”

Theoretical Study on DBU-Catalyzed Insertion of Isatins into Aryl Difluoronitromethyl Ketones: A Case for Predicting Chemoselectivity Using Electrophilic Parr Function

“…All of the theoretical calculations were carried out in the Gaussian 09 suite of programs. 46 All of the stationary points were optimized by DFT method, which has been proved to be a powerful tool for clarifying the detailed reaction mechanisms in enzymes, 47−51 transition metals, 30,52−58 organocatalysts 27−33,36,53,59−68 catalyzed reactions, and other theoretical studies. 69−76 All of the species were optimized with M06-2X 77−79 density functional and 6-31G(d, p) basis set in chloroform solvent using the integral equation formalism polarizable continuum model (IEF-PCM).…”