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

Sean P. Larmore, Pier Alexandre Champagne

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2 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)6947-6954
Number of pages8
JournalJournal of Organic Chemistry
Issue number11
StatePublished - Jun 2 2023

All Science Journal Classification (ASJC) codes

  • Organic Chemistry


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