Mechanistic evaluation of the halocyclization of 4-penten-1-ol by some Bis(2-substituted pyridine) and Bis(2,6-disubstituted pyridine)bromonium triflates

The halocyclization reaction of 4-penten-1-ol mediated by various bis(2-substituted pyridine) and (2,6- disubstituted pyridine)bromonium triflates (P(2)Br(+)OTf(-)) was investigated to determine the influence of the substituents on the mechanism of reaction. In all cases, the reaction proceeds via a two-step process where the starting P(2)Br(+) reversibly dissociates to a reactive monosubstituted PBr(+), which then is captured by 4-penten-1-ol to form halocyclized product (2-bromomethyltetrahydrofuran). The dissociation rate constant of P(2)Br(+) (k(d)) is sensitive to the steric bulk at the 2- and 6-positions, and in the case of the 2, 6-dicyclohexylpyridine or 2,6-dicyclopentylpyridine, the P(2)Br(+) species are too unstable to isolate. The partitioning ratio of the reactive intermediate (PBr(+)) between reversal and product formation (k(-)(d)/k(2)) is not particularly sensitive to the nature of the pyridine, the limiting values being 3-7 except in the case of bis(2(-)-menthylpyridine)bromonium triflate where the k(-)(d)/k(2) ratio is approximately 80. The reaction of 4-penten-1-ol and its OD isotopomer with bis(lutidine)bromonium triflate was investigated to determine the deuterium kinetic isotope effect (dkie) on the bromocyclization reaction. The (k(-)(d)/k(2))(H/D) ratio is 1.0, indicating that the rate-limiting step for the bromocyclization is probably formation of a PBr(+)-4-penten-1-ol complex which does not involve substantial changes in the bonding of the OH. The cyclization of 4-penten-1-ol and 4-pentenoic acid mediated by bis(2(-)-menthylpyridine)bromonium triflate produces an enantiomeric excess in the cyclized products of only 2.4% and 4.8% respectively.