Carbon Bond Catalysis: Dialkyl Sulfates, Alkyl Sulfonates and Alkyl Hal-ides as Catalysts in Acetal Forming and Related Reactions

Abstract

This study demonstrates a previously unexplored facet of sp3-carbon electrophiles (or alkylating agents): their potential for catalytic applications through carbon-bond interactions. In contrast to their classical SN1 and SN2 reactions, we present an al-ternate perspective, the catalytic nature of alkyl electrophiles through noncovalent interactions (NCIs). The involvement of NCIs by carbon electrophiles (possessing polar Csp3-X bonds) in stabilizing conformations of small molecules and biomole-cules has recently been discovered. Nevertheless, their catalytic role in activating small molecules has not been observed. As the "X" group evolves into an effective leaving group, carbon electrophiles develop strong positive potentials on the carbon surface (σ-hole). However, small atomic size and steric congestion resulting from the presence of four groups around the carbon atom pose challenges in establishing strong σ-hole interactions with nucleophilic acceptors. This unique behavior of alkyl electrophiles has deterred chemists from exploring their potential as catalysts in chemical transformations. In groundbreaking revelation, we demonstrate for the first time that alkyl electrophiles function as Lewis acid catalysts in activating carbonyls for acetal formation and related reactions through NCIs. We meticulously chose a range of alkyl electrophiles and discovered a striking correlation between their molecular electrostatic potential (MEP) surface energies and their catalytic efficacy in acetal-forming reactions. Our comprehensive approach, which encompassed both experimental and theoretical investigations, provided robust support for the catalytic potential of alkyl electrophiles through non-covalent carbon bond interactions.