Stereoselective Construction of Tertiary Homoallyl Alcohols and Ethers by Nucleophilic Substitution at Quaternary Carbon Stereocenters

Abstract

An efficient method for the stereoselective construction of tertiary CÀ O bonds via a stereoinvertive nucleophilic substitution at the quaternary carbon stereocenter of cyclopropyl carbinol derivatives using water, alcohols and phenols as nucleophiles has been developed. This substitution reaction proceeds under mild conditions and tolerates several functional groups, providing a new access to the stereoselective formation of highly congested tertiary homoallyl alcohols and ethers.

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. 44 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. [45][46][47][48][49][50] Our group studied this system computationally and showed that CPC intermediate VIII is responsible for the observed selectivity. 51 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.…”