No abstract

The thiol–ene reaction is one of the fundamental reactions in biochemistry and synthetic organic chemistry. In this study, the effect of polar media on the reaction kinetics is taken into account by using the transition state theory; the reactivities of the carbon and sulfur radicals have also been rationalized by using conceptual DFT. The results have shown that the solvents have more impact on hydrogen atom transfer reactions and the chain transfer rate constant, k CT, can be increased by using nonpolar solvents, while propagation reactions are less sensitive to media. Similarly, the k P/k CT ratio can be manipulated by changing the environment in order to obtain tailor-made polymers. Regarding the DFT descriptors, the local and global electrophilicity indices are well correlated with the propagation rate constant k P, whereas the global electrophilicity index is associated with the chain transfer rate constant k CT. Overall, electrophilicity indices can be used with confidence to predict the kinetics of thiol–ene reactions

Activated phenolic esters are promising as lysine-targeted covalent inhibitors of the PI3Kδ enzyme. Quantum chemical calculations on model reactions provide insights into the reaction mechanisms and factors determining inhibitor efficiency.

Thiol-yne reactions have drawn attention because of the click nature as well as the regular step-growth network nature of their products, despite the radical-mediated reactant. However, the factors governing the reaction pathways have not been examined using quantum chemical tools in a comprehensive manner. Thereupon, we have systematically investigated the mechanism of thiol-yne reactions, focusing on the structural influences of thiol and alkyne functionalities. The reaction kinetics, structure–reactivity relations, and E/Z diastereoselectivity of the products have been enlightened for the first cycle of the thiol-yne polymerization reaction. For this reason, a diverse set of 11 thiol-yne reactions with four thiols and eight alkynes was modeled by means of density functional theory. We performed a benchmark study and determined the M06-2X/6-31+G­(d,p) level of theory as the best cost-effective methodology to model such reactions. Results reveal that spin density, the stabilities of sulfur radicals for propagation, and the stability of alkenyl intermediate radicals for the chain transfer are the determining factors of each reaction rate. Intramolecular π–π stacking interactions at transition-state structures are found to be responsible for Z diastereoselectivity.