Synthesis of Bis-spirocyclic Derivatives of 3-azabicyclo[3.1.0]hexane Via Cyclopropene Cycloadditions to the Stable Azomethine Ylide Derived from Ruhemann's Purple

Overview

Journal Beilstein J Org Chem

Specialty Chemistry

Date 2022 Jul 21

PMID 35859623

Authors

Alexander S Filatov

Olesya V Khoroshilova

Anna G Larina

Vitali M Boitsov

Alexander V Stepakov

Affiliations

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Abstract

A reliable method for the synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexanes through the 1,3-dipolar cycloaddition (1,3-DC) reactions of cyclopropenes to the stable azomethine ylide - protonated form of Ruhemann's purple (PRP) has been developed. Both 3-substituted and 3,3-disubstituted cyclopropenes reacted with PRP, affording the corresponding bis-spirocyclic 3-azabicyclo[3.1.0]hexane cycloadducts in moderate to good yields with high diastereofacial selectivity. Moreover, several unstable 1,2-disubstituted cyclopropenes were successfully trapped by the stable 1,3-dipole under mild conditions. The mechanism of the cycloaddition reactions of cyclopropenes with PRP has been thoroughly studied using density functional theory (DFT) methods at the M11/cc-pVDZ level of theory. The cycloaddition reactions have been found to be HOMO-LUMO controlled while the transition-state energies for the reaction of 3-methyl-3-phenylcyclopropene with PRP are fully consistent with the experimentally observed stereoselectivity.

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