Cyclopropylcarbinyl-to-Homoallyl Carbocation Equilibria Influence the Stereospecificity in the Nucleophilic Substitution of Cyclopropylcarbinols

The
synthesis of quaternary homoallylic halides and trichloroacetates
from cyclopropylcarbinols, as reported by Marek (J. Am. Chem.
Soc. 2020, 142, 5543–5548),
is one of the few reported examples of stereospecific nucleophilic
substitution involving chiral bridged carbocations. However, for the
phenyl-substituted substrates, poor specificity is observed and mixtures
of diastereomers are obtained. To understand the nature of the intermediates
involved and explain the loss of specificity for certain substrates,
we have performed a computational investigation of the reaction mechanism
using ωB97X-D optimizations and DLPNO-CCSD(T) energy refinements.
Our results indicate that cyclopropylcarbinyl cations are stable intermediates
in this reaction, while bicyclobutonium structures are high-energy
transition structures that are not involved. Instead, multiple rearrangement
pathways of cyclopropylcarbinyl cations were located, including ring
openings to homoallylic cations. The activation barriers required
to reach such structures are correlated to the nature of the substituents;
while direct nucleophilic attack on the chiral cyclopropylcarbinyl
cations is kinetically favored for most systems, the rearrangements
become competitive with nucleophilic attack for the phenyl-substituted
systems, leading to a loss of specificity through rearranged carbocation
intermediates. As such, stereospecific reactions of chiral cyclopropylcarbinyl
cations depend on the energies required to access their corresponding
homoallylic structures, from which selectivity is not guaranteed.