A Density Functional Theory Study on Et-BAC-Catalyzed 1,6-Conjugate Addition of p-Chlorobenzaldehyde to p-Quinone Methide for the Synthesis of α,α'-Diarylated Ketones.

Umpolung-based organocatalysis has made a remarkable breakthrough in the field of synthetic organic chemistry. Among a plethora of umpolung catalysts, bis(amino)cyclopropenylidenes (BACs) have emerged as efficient organocatalysts with potential applications in synthesizing numerous essential organic moieties. In this study, a plausible mechanism for bis(diethylamino)cyclopropenylidene (Et-BAC)-catalyzed synthesis of α,α'-diarylated ketones has been established using the density functional theory (DFT) method. The proposed catalytic cycle of the studied reaction initiates with the nucleophilic interaction of Et-BAC with p-chlorobenzaldehyde to form a zwitterionic intermediate, which is then transformed to a reactive Breslow intermediate. The Breslow intermediate further undergoes a chemoselective and stereoselective 1,6-conjugate addition reaction with p-quinone methide to form a new C-C bond connection. Finally, the generated adduct undergoes a proton shift reaction with the assistance of both 8-diazabicyclo(5.4.0)undec-7-ene (DBU) and protonated DBU to yield the desired product. Conceptual DFT-derived reactivity indices and frontier molecular orbital theory analysis have been successfully utilized to unravel the role of Et-BAC in this studied reaction. In addition to Et-BAC, DBU and protonated DBU also play a very important role in lowering the activation energy barrier of proton transfer steps. This investigation will help in the rational designing of simple nonheterocyclic carbene-mediated novel organic transformations.