Intramolecular nucleophilic addition of carbanions generated from N-benzylamides to cyclopropenes

Abstract

An unusual reaction is described, involving a formal intramolecular nucleophilic substitution of bromocyclopropanes with nitrogen ylides generated in situ from N-benzyl carboxamides. It is shown that this reaction involves cyclopropene intermediates and allows for the facile and expeditious preparation of 3-azabicyclo[3.1.0]hexan-2-one scaffolds.

Formal [3 + 3] Cycloaddition Reactions between Electron-Deficient Cyclopropenes and Hydrazones: A Route to Alkyl 1,4,5,6-Tetrahydropyridazine-3-carboxylates

“…Initially, a cyclopropene intermediate I was generated from the 1,2-elimination of the substrate 1a . Then the reaction likely proceeded through the formation of an enolate anion to adduct II by a aza-Michael addition with reagent 2a , accompanied by ring cleavage . The product 3aa was finally obtained through one of two reaction pathways (path a or b) by subsequent transformation of the key intermediate II .…”

Metal-Templated Assembly of Cyclopropane-Fused Diazepanones and Diazecanones via exo-trig Nucleophilic Cyclization of Cyclopropenes with Tethered Carbamates

“…Synthetic methodology employing 5-exo-trig nucleophilic attack by stabilized carbanions 3 allowing access to bicyclic lactams 4 (Scheme 1, eq 2) was recently developed in our group. 8 We also demonstrated several modes of potassium-templated cyclizations involving nucleophilic alkoxides 5 that afford medium sized cyclic ethers 6 (Scheme 1, eq 3). 9 During these studies, novel scaffolds were identified possessing promising biological activity, 9a which justified further synthetic efforts, especially toward medium sized cyclic amines 8, that could mimic β- or γ- turns of polypeptides.…”

“…The intramolecular version of this reaction involving nucleophilic species tethered to cyclopropenes and leading to the formation of fused bicyclic ring systems is much more challenging. Synthetic methodology employing 5- exo-trig nucleophilic attack by stabilized carbanions 3 allowing access to bicyclic lactams 4 (Scheme , eq 2) was recently developed in our group . We also demonstrated several modes of potassium-templated cyclizations involving nucleophilic alkoxides 5 that afford medium sized cyclic ethers 6 (Scheme , eq 3) .…”

Construction of heterocyclic rings from cyclopropenes

“…A fused heterocyclic scaffolds like 3-azabicyclo[3.1.0]hexan-2-one 174 have been constructed in good yields by treating N -benzyl-2-bromocyclopropane-1-carboxamide 173 with excess amount of freshly sublimed t -BuOK in anhydrous THF containing 18-crown-6 ether. 48 During the reaction, both reactive nitrogen ylides and unactivated cyclopropenes would be readily generated in situ via dehydrohalogenation and deprotonation, then a subsequent intramolecular 5- exo-trig nucleophilic addition quickly took place between the nitrogen ylides and cyclopropenes (Scheme 30).…”