Gas-phase heteroaromatic substitution. 14. Attack of dimethylfluoronium ion on 2- and 3-methyl-pyrroles, -furans, and -thiophenes

Abstract

The gas-phase methylation of 2- and 3-methyl-pyrroles (2P and 3P), -furans (2F and 3F), and -thiophenes (2T and 3T) by (CH3)2F+ ions, from γ radiolysis of CH3F, has been investigated at pressures ranging from 50 to 760 Torr, in the presence of a thermal radical scavenger (O2) and variable concentrations of an added base (NMe3: 0–10 Torr). The mechanism of the methylation process is discussed and the intrinsic positional selectivity of the (CH3)2F+ ions evaluated in the framework of the Charge and Frontier Orbital Control concept. Owing to the very large energy gap between the LUMO of (CH3)2F+ and the HOMOs of the selected heteroaromatic substrates, their gas-phase methylation is characterized by a distinct affinity of the ionic electrophile toward those substrate positions with the highest net negative charge, i.e., the C3 in 2P (100%), the C4 in 3P (100%), the heteroatom of 2F and 3F (>80%), the C5 of 2T (32%), and the C2 of 3T (47%). Analysis of the methylated product distribution from 2F and 3F as a function of the experimental conditions reveals that the interaction of the (CH3)2F+ with the heteroatom of furans gives rise to the reversible formation of two sets of electrostatic adducts, i.e., a "chelate" adduct (III) and a single proton-bonded adduct (IV), the first rapidly evolving to the α-substituted heteroarenium intermediate by proximity effects and the latter slowly rearranging to the chelate structure III. Formation of these categories of electrostatic adducts from furans, which is much less extensive in the case of thiophenes and absent in pyrroles, accounts for the apparent pronounced affinity of gaseous alkylating electrophiles, irrespective of their LUMO energy, for the α carbons of furans. Key words: gas-phase ion chemistry, electrophilic aromatic substitutions, radiolysis, dimethylfluoronium ions, methylated heteroarenes.