A Synergy between Experiment and Theory for the Formation of Pyridine and Pyrrole Derivatives from Selected Butadienes and Organolithium Reagents: Mechanism, Solvent, and Substituent Effect

Abstract

Due to the exponential growth of pyridine and pyrrole use, focus is shifting to more completely understanding their syntheses and toward more effective preparation and application. Herein, we present a series of density functional theory (DFT) models, employing differing treatments of solvent effects, quantitatively characterizing the formation mechanism of a series of pyridine and pyrrole derivatives from multisubstituted 1-cyano-1,3-butadienes and organolithium reagents. Results indicated that pyridine and pyrrole formations are multistep processes, in which the rate-determining step involves a free-energy barrier of 18 kcal·mol−1, as determined using a novel microsolvation method. Both solvent (tetrahydrofuran or ether) and organolithium reagent identity are shown to play instrumental roles in affecting the pyridine/pyrrole product ratios. The microsolvation results are more plausible than those emerging from traditional approaches to treating solvent effects (i.e., dielectric continuum). Specifically,...