Dynamics and the Failure of Transition State Theory in Alkene Hydroboration

Abstract

Transition state theory fails to accurately predict the selectivity in an example where it is ubiquitously invoked, hydroboration. The hydroboration of terminal alkenes with BH 3 is moderately regioselective, affording an 88:12 -90:10 ratio of anti-Markovnikov:Markovnikov adducts. Highlevel ab initio calculations predict too large of an energy difference between anti-Markovnikov and Markovnikov transition structures to account for the observed product ratio, and the consideration of calculational error, solvent, tunneling, and entropy effects does not resolve the discrepancy. Trajectory studies, however, predict well the experimental selectivity. The decreased selectivity versus transition state theory arises from the excess energy generated as the BH 3 interacts with the alkene, and the observed selectivity is proposed to result from a combination of low selectivity in direct trajectories, moderate RRKM selectivity, and high selectivity after thermal equilibration.The hydroboration of simple alkenes with BH 3 preferentially occurs in an "antiMarkovnikov" 1 fashion. The standard explanation for this preference in the literature, 1,2 reproduced in some form in all general textbooks of organic chemistry, is that the selectivity arises from a greater stability for the anti-Markovnikov transition state over the alternative "Markovnikov" transition state. We find here that transition state theory fails to accurately account for the regioselectivity of hydroboration. Instead, a consideration of dynamic trajectories allows understanding of the selectivity.The addition of BH 3 to terminal alkenes is only moderately regioselective. With simple terminal alkenes such as 1-hexene, the ratio of primary to secondary alcohol products after hydroboration with BH 3 at 0 -25 °C followed by oxidation is approximately 94:6. 1,3 This ratio as it has been observed is a composite of the regioselectivity in three separate steps - 4 but they are more regioselective as well, so the initial reaction of BH 3 is less selective than the composite ratio. Using the observed 1-hexanol/2-hexanol ratio of 97:3 for the reaction of n-butylborane with 1-hexene 5 as a measure of the selectivity of the second and third steps of hydroboration, the regioselectivity for reaction of 1-hexene with BH 3 itself would be ≈88:12. In our hands, the hydroboration of propene-d 6 at 21 °C with 100 equiv of BH 3 •THF (to minimize the contribution of hydroboration by alkylboranes) affords a 90.0:10.0 ratio of primary and secondary alcohols (based on direct analysis of the oxidized reaction mixture by 2 H NMR). Assuming the applicability of transition state theory, the ΔΔG ‡ for the transition states leading to the two products would be 1.1 -1.3 kcal/mol.A variety of gas-phase computational approaches were explored in an attempt to predict this ΔΔG ‡ . 6 CCSD(T)/aug-cc-pvdz calculations were used to locate transition structures 1 ‡ and 2 ‡ for formation of the regioisomeric products from the precursor complex 3. The relative energetics of the anti-Markovnik...

The Study of Reactive Intermediates in Condensed Phases

“…This is formed in an exothermic bimolecular step after dissociation of the ether solvent from the borane, and is thereby initially formed with excess internal energy, of roughly 11 kcal/mol. 117 From this common intermediate, reaction can proceed over two different transition states, one leading to the primary borane, and one to the secondary isomer. Because both barriers are very low, reaction proceeds very rapidly, in several ps.…”

“…Indeed, there is some suggestion that the reaction has partial ballistic or dynamical character, with barrier crossing occurring impulsively immediately without any vibrational energy randomization within the intermediate. 117 This was suggested to account for the observed ratio of the two isomers, of roughly 9:1, which differs significantly from the 99:1 ratio expected for a thermal reaction, based on accurate quantum chemical calculations that yield a difference in standard free energies for the two competing TSs of 2.5 kcal/mol. However, it is also possible to account for the observed ratio of products by taking into account the incomplete thermalization of the intermediate.…”

Non-equilibrium reaction and relaxation dynamics in a strongly interacting explicit solvent: F + CD3CN treated with a parallel multi-state EVB model

“…[20][21][22] For example, there is good evidence that thermal reactions as well-known as alkene hydroboration have a Markovnikov/AntiMarkovnikov product ratio which is determined by the extent of nascent vibrational excitation in the short lived addition complex. 12,23 Recently, it has even been suggested that solute/solvent interactions which take place in the course of transient vibrational relaxation dynamics provide a route to enantioselective amplification. 19 Accurately simulating reaction dynamics in coupled solute/solvent environments remains a challenge within the field of computational and theoretical chemistry, 14,16,[24][25][26] mostly owing to the fact that it is difficult to construct a potential energy surface (PES) whose balanced accuracy and efficiency is sufficient to interpret experiments.…”

Deviation from the anti-Markovnikov rule: a computational study of the regio- and stereoselectivity of diene hydroboration reactions

“…1 and assuming a kinetically controlled mechanism, we can predict the most favorable isomers computationally [21,22]. Previous computational studies have also pointed out the fact that the final thermodynamically favored products might not reflect the selectivity of the kinetically favored hydroboration reactions [23] and emphasized the importance of dynamical effects beyond transition state theory [24][25][26].…”