The concern of emergence of multi-station reaction pathways that might make stepwise the mechanism of the 1,3-dipolar cycloadditions of azides and alkynes

• Published in: Journal of molecular structure 2018-03, Vol.1155, p.58-64
• Main Authors: Mohtat, Bita, Siadati, Seyyed Amir, Khalilzadeh, Mohammad Ali, Zareyee, Daryoush
• Format: Article
• Language: English
• Subjects: 1,3-Dipolar cycloaddition; Azides; BOMD simulation; Debates on the mechanism; Stepwise reaction pathways
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2017.10.034

After hot debates on the concerted or stepwise nature of the mechanism of the catalyst-free 1,3-dipolar cycloadditions (DC)s, nowadays, it is being believed that for the reaction of each dipole and dipolarophile, there is a possibility that the reaction mechanism becomes stepwise, intermediates emerge, and the reaction becomes non-stereospecific. Yield of even minimal amounts of unwanted side products or stereoisomers as impurities could bring many troubles like difficult purification steps. In this project, we have made attempts to study all probable reaction channels of the azide cycloadditions with two functionalized alkynes, in order to answer this question: "is there any possibility that intermediates evolve in the catalyst-free click 1,3-DC reaction of azide-alkynes?". During the calculations, several multi-station reaction pathways supporting the stepwise and concerted mechanisms were detected. Also, the born–oppenheimer molecular dynamic (BOMD) simulation was used to find trustable geometries which could be emerged during the reaction coordinate. [Display omitted] •The concern for the probability of production of unwanted stereoisomers as side products during the switching behavior of the mechanism of the widely used catalyst-free 1,3-dipolar cycloaddition process between some azides and alkynes from concerted to stepwise, were investigated.•In order find any probable species emerging during the reaction coordinate, the BOMD simulation was developed.•Dozens of geometries with different dihedral angles, orientations, and fragmental distances, were proposed and designed as input files and then optimized to give any possible meta-stable or stable states which could be emerged during the reactions progress.•All of the probable reaction channels were examined by calculations to find any possible pathways for the non-catalyzed click 1,3- dipolar cycloaddition between hydrogen azide and some functionalized alkynes.