Absolute Rate Constants for Hydrogen Atom Transfer from Tertiary Amides to the Cumyloxyl Radical: Evaluating the Role of Stereoelectronic Effects

A time-resolved kinetic study of the hydrogen atom transfer (HAT) reactions from a series of alkanamides to the cumyloxyl radical (CumO(center dot)) was carried out. With N,N-dialkylformamides HAT preferentially occurs from the formyl C-H bond, while in N-formylpyrrolidine HAT mostly occurs from the ring alpha-C-H bonds. With the acetamides and the alkanamides almost exclusive HAT from the C-H bonds that are alpha to nitrogen was observed. The results obtained show that alignment between the C-H bond being broken and the amide pi-system can lead to significant increases in the HAT rate constant (k(H)). This finding points toward the important role of stereoelectronic effects on the HAT reactivity and selectivity. The highest k(H) values were measured for the reactions of CumO(center dot) with N-acylpyrrolidines. These substrates have ring alpha-C-H bonds that are held in a conformation that is optimally aligned with the amide pi-system, thus allowing for the relatively facile HAT reaction. The lowest k(H) value was measured for the reaction of N,N-diisobutylacetamide, wherein the steric bulk associated with the N-isobutyl groups increases the energy barrier required to reach the most suitable conformation for HAT. The experimental results are well supported by the computed BDEs for the C-H bonds of the most representative substrates.