Lewis Acid‐Catalyzed Stereoselective [7+7] Intermolecular Cyclization of Aniline‐Tethered Alkylidenecyclopropanes: A One‐Step Synthetic Protocol of 14‐Membered Macrocyclic Dimers

Abstract

Ao ne-step stereoselective synthetic methodo f 14-membered aza-macrocyclicdimers has been developed by aL ewis acid-catalyzed ring-opening and intermolecular cyclization reactiono fa niline-tethered alkylidenecyclopropanes, affording 14-membered aza-macrocyclic dimers (mainly as E-configuration) in moderate to good yields under mild conditions.

The Construction of Molecular Complexity from Functionalized Alkylidenecyclopropanes (FACPs)

“…Different from the classical reaction model that alkylidenecyclopropanes could act as a 1,3‐dipole in the presence of Lewis acid or Brønsted acid catalysts, the aniline‐tethered alkylidenecyclopropanes 1 were shown as a novel 1,7‐dipole upon Lewis acid catalysis, which could be employed for the synthesis of the challengeable aza‐macrocyclic compounds 49 after intermolecular cyclization (Scheme ) …”

“…Different from the classical reactionm odel that alkylidenecyclopropanes could act as a1 ,3-dipole in the presence of Lewis acid or Brønsted acid catalysts, the aniline-tethered alkylidenecyclopropanes 1 were shown as an ovel 1,7-dipole upon Lewis acid catalysis, which couldb ee mployed for the synthesis of the challengeable aza-macrocyclic compounds 49 after intermolecular cyclization (Scheme 12). [13] Since our group in 2012 disclosed the [3+ +2] cycloaddition of an in situ generated imine with aniline-tethered alkylidenecyclopropanes 1, [14] as eries of reports demonstrated that ac onsecutive 6p electrocyclization and rearrangement occurred once allene-type FACPs 50 weref ormed during the reaction process. For example, our group has reported that the in situ generated isocyanate 50 a,i sothiocyanate 50 b,a nd carbodiimide 50 c could undergo formal [3+ +2] cycloaddition reactions to give furoquinolines 52 a,t hienoquinolines 52 b, and pyrroquinolines 52 c,r espectively [Scheme 13, Eqs.…”

Lewis Acid-Mediated Formation of 1,3-Disubstituted Spiro[cyclopropane-1,2′-indanes]: The Activating Effect of the Cyclopropane Walsh Orbital

“…Alkylidenecyclopropanes are highly strained molecules, although stable enough to allow their use in a variety of synthetic applications. − Indeed, a plethora of applications for these reactive species have been disclosed in the past few years. − Benzylidenecyclopropanes functionalized at the ortho position provide an opportunity for exploring intramolecular cyclizations involving both the 4-carbon methylidenecyclopropane fragment and the nearby functional group at the benzene ring. Among this class of compounds, those bearing ortho -amino/amido groups or other N -linked functionalities are perhaps the most widely explored, mainly as a result of investigations by the Shi group. − In marked contrast, only fivea very scarce numberof ortho -formyl substituted benzylidenecyclopropanes are known, and their synthetic usefulness has rarely been studied. − Moody was the first to prepare 2-(cyclopropylidenemethyl)­benzaldehyde 1 in 1987, starting with a monoethyleneacetal derived from o -phthalaldehyde via a Wittig reaction with cyclopropyltriphenylphosphonium bromide followed by acetal hydrolysis, and utilized it in his α-azidocinnamate synthetic methodology for preparing indoles and isoquinolines (Scheme a). Twenty years later, Fürstner also synthesized 1 , starting from 1,2-bis­(hydroxymethyl)­benzene.…”