Density functional theory study of the mechanism of the BF3-catalyzed rearrangement of 2,3,3-trimethyl-1,2-epoxybutane to 2,3,3-trimethylbutanal

The potential energy surface for the rearrangement of BF3-coordinated 2,3,3-trimethyl-1,2-epoxybutane to 2,3,3-trimethylbutanal has been investigated at the B3LYP/6-31G* level of theory. SCRF(SCI-PCM) solvent calculations and theoretical primary and secondary kinetic isotope effects at the same level of theory provide support for a two-step process with ring opening of the BF3-coordinated epoxide to a tertiary carbocation intermediate followed by hydride/deuteride migration to give aldehyde. The experimentally measured primary isotope effect (k(H)D/k(D)H) requires a correction for an appropriate secondary isotope effect to give a true isotope effect k(H)(H)/k(D)(H). For the lowest energy pathway for hydride migration, the calculated secondary kinetic isotope effect is 0.92, which when applied to the experimentally measured isotope effect of k(H)(D) /k(D)H = 1.73 gives a revised "true" primary kinetic isotope effect of k(H)(H)/k(D)(H) = 1.59. This compares with a calculated value of 2.01. From intermediate 15, migration of the C1-H-a proton via 19 is energetically favored over C1-H-b migration via 18 and this result is consistent with the experimental results in which hydride migration of the proton cis to the methyl is favored.