Highly Diastereoselective Preparation of Tertiary Alkyl Thiocyanates en Route to Thiols by Stereoinvertive Nucleophilic Substitution at Nonclassical Carbocations

Stereoinvertive SN1 Through Neighboring Group Participation

“…[35] Upon treating stereodefined cyclopropane 40 with a catalytic amount of Lewis acid, the addition of a nucleophile yields homoallyl product 42, with a complete inversion of configuration at the β-quaternary center (the αcenter is converted into an alkene). This transformation can be conducted with a wide variety of nucleophiles, including alkyls, [36] alcohols, [38] carboxylates, [35] halogens, [35] nitrogen [38] and sulfur [39] based nucleophiles. Moreover, this transformation can be extended to the preparation of acyclic products with high enantioselectivity.…”

Substituent Effects on the Equilibria between Cyclopropylcarbinyl, Bicyclobutonium, Homoallyl, and Cyclobutyl Cations

“…For instance, Feringa, Houk and Fujita reported in 2018 that cycloheptenyl bromide III undergoes an enantiospecific rearrangement to its cyclohexenyl derivative IV under Lewis acid catalysis, a process that involves CPC cation V . Similarly, Marek has published a series of reports starting in 2020, discussing how cyclopropylcarbinols VI form homoallylic products VII with high diastereoselectivity, as long as no aromatic substituent is located at the R 3 or R 4 positions. − Our group studied this system computationally and showed that CPC intermediate VIII is responsible for the observed selectivity . This cation only rearranges faster than nucleophilic trapping when R 3 is an aryl substituent, which enables a classical homoallylic cation to intervene, leading to reduced specificity.…”

Stereoselective Nucleophilic Halogenation at CF3-Substituted Nonclassical Carbocation

“…Therefore, the development of efficient methodologies for synthesizing stereogenic fluorinated building blocks remains an important objective in organic chemistry . Inspired by previous results from our group in controlling the stereochemistry of S N 1 reactions involving nonclassical carbocations (Scheme b), we wondered whether we could employ a similar strategy to prepare acyclic molecular backbones containing the CF 3 groups with adjacent stereocenters, alongside additional halogens, including fluorine (Scheme c). Indeed, we have recently reported that cyclopropyl carbinol derivatives 1 featuring a quaternary carbon stereocenter at C 4 undergo a smooth Lewis acid-catalyzed ring opening, resulting in the formation of the nonclassical cyclopropylcarbinyl carbocation intermediate CPC .…”