Insights into isothiourea-catalyzed asymmetric [3 + 3] annulation of α,β-unsaturated aryl esters with 2-acylbenzazoles: mechanism, origin of stereoselectivity and switchable chemoselectivity

• Published in: Catalysis science & technology Vol. 1; no. 11; pp. 3664 - 3669
• Main Authors: Wang, Congcong, Li, Shi-Jun, Zhang, Qiao-Chu, Wei, Donghui, Ding, Lina
• Format: Journal Article
• Language: English
• Published: Cambridge Royal Society of Chemistry 08.06.2020
• Subjects: Aromatic compounds; Asymmetry; Carbonyls; Catalysts; Chemical reactions; Covalent bonds; Density functional theory; Esters; Heterocyclic compounds; Mathematical analysis; Organic chemistry; Stereoselectivity
• ISSN: 2044-4753; 2044-4761
• DOI: 10.1039/d0cy00295j

Recently, isothiourea-catalyzed asymmetric [3 + 3] annulation reactions of α,β-unsaturated aryl esters with 2-acylbenzothiazole (or 2-acylbenzoxazole) were reported with switchable chemoselectivity to form either dihydropyridone or dihydropyranone, but predicting the origin of chemoselectivity and stereoselectivity is still challenging in these kinds of reactions. Herein, density functional theory (DFT) was used to study the general mechanism and explore the origin of stereoselectivity and chemoselectivity in these reactions. The calculated results show that three stages including adsorption, [3 + 3] annulation and dissociation are involved in the reaction, and the C-C bond formation involved in [3 + 3] annulation is a key step that determines both chemoselectivity and stereoselectivity. The origin of stereoselectivity was further investigated by analysis of distortion and non-covalent interactions (NCI), and the C-H O interaction between the chiral substituents of the catalyst and the carbonyl oxygen on 2-acylbenzazoles contributes greatly to the stereoselectivity. In addition, the switchable chemoselectivity associated with the competitive [3 + 3] cyclizations for formation of N - and O -heterocyclic compounds can be predicted by using local nucleophilic Parr function ( P k − ) and nucleophilic atom energy ( E a − ) analysis. This work provides guidance for the rational design of potential catalysts for such highly stereoselective reactions with switchable chemoselectivities. The switchable chemoselectivity of isothiourea-catalyzed asymmetric [3 + 3] annulation of α,β-unsaturated aryl esters with 2-acylbenzazoles has been predicted successfully.