Using Bases as Initiators to Isomerize Allylic Alcohols: Insights from Density Functional Theory Studies

Allylic alcohols, as common and readily available building blocks, could be converted into many widely used carbonyl compounds through isomerization reactions. However, these processes often involve expensive transition metal (TM) complexes as the catalyst. What is the bottleneck in the mechanism when no TM is used? In this study, density functional theory (DFT) was employed to explore the mechanistic patterns of allylic alcohols catalyzed using bases, such as KOH, NaOH, LiOH, tBuOK, tBuONa, tBuOLi, 1,5,7-triazabicyclo[4.4.0]dec-5-ene, 1,3,4,6,7,8-hexahydro-1-methyl-2H-pyrimido[1,2-a]pyrimidine, and 1,8-diazabicyclo[5.4.0]undec-7-ene. Our results show that bases containing metal cations follow the metal cation-assisted (MCA) mechanism, whereas organic bases without metal cations follow the ion pair-assisted (IPA) mechanism. The catalytic efficiency of bases containing metal cations is higher than that of bases without metal cations, indicating that metal cations play an important role in the reaction. Additionally, the modulation of substituents R₁ and R₂ in the substrate reveals that electron-withdrawing groups are favorable for C-H bond cleavage, and electron-donating groups are favorable for hydrogen transfer. To better understand these patterns, we applied the DFT and information-theoretic approach (ITA) to examine the impact of bases and substrate substituents on the reactivity of allylic alcohol isomerization. This work should provide a much-needed theoretical guidance to design better non-TM catalysts for the isomerization of allylic alcohols and their derivatives.