Enantioselective synthesis of 1,2,4-triazolines catalyzed by a cinchona alkaloid-derived organocatalyst

Abstract

An enantioselective organocatalytic process for the one-step synthesis of poly-substituted 1,2,4-triazolines is reported. The heterocycle formation is believed to go through a step-wise mechanism of nucleophilic addition of an azlactone to an azodicarboxylate in the presence of an organic base catalyst, followed by a TMSCHN2 mediated heterocyclization. Both theoretical calculations and experimental evidence suggest the pre-organization of the transition state for the chirality determining step via a unique 7-membered intramolecular hydrogen bonding.

Enantioselective Construction of Multi-Nitrogen-Containing Spirocycles: Asymmetric [3+2] Annulation of 4-Isothiocyanato­pyrazolones with Azodicarboxylates

“…7 In 2010, a preliminary asymmetric version for the synthesis of triazolines was reported by Jørgensen and co-workers. 7a After that, some elegant methods for the asymmetric synthesis of triazoline derivatives using isocyano esters, oxazoles, and isothiocyanates as building blocks in the reaction with azodicarboxylates have been developed by Feng, 7b f Huang, 7c Shi, 7d,e and Guo 7g groups (Scheme 1, a ). Among them, mostly triazoline structures bearing a quaternary carbon atom containing carboxylates functional group were synthesized.…”

Formal [3 + 2] Cycloaddition of α-Imino Esters with Azo Compounds: Facile Construction of Pentasubstituted 1,2,4-Triazoline Skeletons

“…Furthermore, it is a useful precursor for synthesizing 1,2,4-triazole [19]. Therefore, efficient synthesis methods for 1,2,4-triazolines have been investigated [19][20][21][22][23][24][25][26]. In 2017, Li, Tang, and co-workers reported the visible-light-induced cyclization of azirines with azodicarboxylate, which formed the corresponding 1,2,4-triazolines in high yields [26].…”