The Intramolecular Aromatic Electrophilic Substitution of Aminocyclopropanes Prepared by the Kulinkovich–de Meijere Reaction

Abstract

This article describes new examples of intramolecular Kulinkovich–de Meijere reactions applied to carboxylic amides bearing an olefin moiety and an aromatic ring at a suitable position. Upon heating, the aminocyclopropanes thus obtained undergo intramolecular aromatic electrophilic substitution to afford polycyclic systems. Among the various starting materials prepared, best results are obtained from indole and phenol derivatives. In each case, a benzylic quaternary centre is introduced at the newly‐formed ring junction. On one example, the efficiency of the cyclisation has been dramatically improved using a catalytic amount of para‐toluenesulfonic acid. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Ring-opening, cycloaddition and rearrangement reactions of nitrogen-substituted cyclopropane derivatives

“…The variable diastereoselectivities observed, in particular as a function of the reaction time, suggest that this cyclisation step is reversible. 69 Like in the process described in the preceding paragraph, only a catalytic amount of a proton source is in principle necessary and these reactions can sometimes proceed without introducing any acid reagent in the reaction medium. For instance, a phenol substrate and the corresponding product 23a (entry 1) are evidently acidic enough to catalyse the reaction.…”

“…Under thermal conditions, bicyclic aminocyclopropane substrates 22 fitted with an electron-rich aryl group at a suitable distance are converted into polycyclic nitrogen-containing heterocycles 23 (Table 3). 69,70 The mechanism of these transformations is likely to proceed by aromatic electrophilic substitution, the iminium function of the intermediate 24 playing the role of the incoming electrophile. The variable diastereoselectivities observed, in particular as a function of the reaction time, suggest that this cyclisation step is reversible.…”

Transition metals in organic synthesis: Highlights for the year 2005

“…(116)) [761]. Titanium mediated intramolecular cyclopropanations of alkene tethered amides [762]. A titaniummediated cyclopropanation of nitriles with Grignard reagents to give amino-substituted cyclopropanes was described [763].…”

Synthesis and Reactivity of Donor-Acceptor Substituted Aminocyclopropanes and Aminocyclobutanes

“…Six and co-workers reported in 2005 the intramolecular cyclization of aminocyclopropanes with electron-rich aromatics under thermal conditions (Scheme 1.56) [213]. By heating substrates 175 and 177 in chlorobenzene, they obtained the tricyclic products 176 and 178 in 67 and 49 % yield respectively.…”