The synthesis of quaternary homoallylic halides and trichloroacetates from cyclopropylcarbinols, as reported by Marek in 2020 (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 the stereoselectivity of the reaction is poor and a mixture of diastereomers is obtained. In order to understand the nature of the intermediates involved in this transformation and explain the loss of selectivity for certain substrates, we have performed a Density Functional Theory investigation of the reaction mechanism at the DLPNO-CCSD(T)/Def2TZVPP level of theory. Our results indicate that cyclopropylcarbinyl cations are stable intermediates in this reaction, while bicyclobutonium structures are high-energy transition structures and as such are not involved, regardless of the substitution pattern on the substrate. Instead, multiple rearrangement pathways of cyclopropylcarbinyl cations have been located, including rotations around their π-bonds and ring openings to homoallylic cations. Importantly, the relative energies of these homoallylic cations and of the activation barriers to reach them are correlated to the nature of the substituents. While direct nucleophilic attack on the chiral cyclopropylcarbinyl cation is kinetically favored for most systems, the rearrangements become competitive with nucleophilic attack for the phenyl-substituted systems, leading to a loss of selectivity through a mixture of rearranged carbocation intermediates. As such, it appears that stereospecific reactions of chiral cyclopropylcarbinyl cations depend on the ability of these cations to access homoallylic structures, from which selectivity is not guaranteed.

The synthesis of quaternary homoallylic halides and trichloroacetates from cyclopropylcarbinols, as reported by Marek in 2020 (J. Am. Chem. Soc. 2020, 142, 5543-5548), is one of the few reported examples of stereospecific nucleophilic substitution on chiral non-classical carbocations. However, for the phenyl-substituted substrates the stereoselectivity of the reaction is lost and a mixture of diastereomers is obtained. In order to understand the nature of the intermediates in-volved in this transformation and explain the loss of selectivity for certain substrates, we have performed a Density Func-tional Theory investigation of the reaction mechanism at the ωB97X-D/Def2TZVPP and M06-2X/Def2TZVPP levels of theory. Our results indicate that non-classical cyclopropylcarbinyl cations are stable intermediates in this reaction, while bicyclobutonium structures are high-energy transition structures and as such are not involved, regardless of the substitu-ent pattern on the substrate. Instead, multiple rearrangement pathways of cyclopropylcarbinyl cations have been located, including rotations around their π-bonds and ring openings to classical homoallylic cations. Importantly, the relative energies of these homoallylic cations and of the activation barriers to reach them are correlated to the nature of the sub-stituents. While direct nucleophilic attack on the chiral cyclopropylcarbinyl cation is kinetically favored for most sys-tems, the rearrangements become competitive with nucleophilic attack for the phenyl-substituted systems, leading to a loss of selectivity through a mixture of rearranged carbocation intermediates. As such, it appears that stereospecific reac-tions of chiral non-classical cyclopropylcarbinyl cations depend on the ability of these cations to access classical homoallylic structures, from which selectivity is not guaranteed.

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 phenylsubstituted 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.

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