A Mild Procedure for the Lewis Acid-Catalyzed Ring-Opening of Activated Cyclopropanes with Amine Nucleophiles

Abstract

The Lewis acid-catalyzed ring-opening of methyl 1-nitrocyclopropanecarboxylates with amine nucleophiles is described. The reaction proceeds at room temperature and with complete preservation of the enantiomeric purity from the electrophilic center of the cyclopropane to the acyclic product. The methodology was applied in an enantioselective synthesis of the dual serotonin/norepinephrine reuptake inhibitor (3R)-3-(1 H-indol-1-yl)- N-methyl-3-phenylpropan-1-amine.

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

“…Ni(ClO 4 ) 2 was identified as sufficiently active to allow the reactions to be performed at room temperature. 287 Importantly, this Lewis acid is mild enough to minimise heterolytic bond cleavage of the cyclopropane substrate.…”

“…The value of this method is illustrated by an application to the synthesis of the neurotransmitter reuptake inhibitor 177 (Scheme 120). 287 To improve ring-opening reactions using phenol derivatives as nucleophiles, several bases were investigated, and cesium carbonate was found to give the best results. Again, these transformations take place without erosion of enantiomeric purity, when non-racemic substrates are engaged, and neat inversion is observed.…”

Ring Opening of Donor–Acceptor Cyclopropanes with N-Nucleo­philes

“…The Charette group demonstrated 80 that additional catalytic activation of nitrocyclopropanecarboxylates 50 allowed substantial relaxation in the conditions of their cleavage with amines in comparison with the methods suggested by Seebach and Dailey. 67,69 For instance, it was established that the ring in 1-nitro-2-phenylcyclopropane-1-carboxylate 50а was opened by aniline upon continuous heating at 90 °С, while the introduction of nickel(II) perchlorate hexahydrate as a catalyst allowed this reaction to complete at room temperature at an even higher rate (Scheme 20).…”

“…82 The Tang group has developed an asymmetric catalytically induced version for the nucleophilic ring opening of activated cyclopropanes with amines. [84][85][86] Conditions analogous to those suggested in Charette's method 80 facilitated ring opening for cyclopropane-1,1-diesters 57a-n by secondary amines yielding 58а-w. Notably, the most convenient yield/enantiomeric excess relationship for products 58 was achieved upon employing tris-indaneoxazoline 59 as a ligand for asymmetric induction (Scheme 26).…”

“…113 The introduction of Ni(ClO 4 ) 2 ·6H 2 O as a catalyst, analogously to Charette's technique for the ring opening of 1-nitrocyclopropane-1-carboxylates 50 (Scheme 20), 80 provided the optimal conditions for this reaction. The use of the catalyst resulted, in most cases, in significantly milder heating conditions and also a reduction in the time for the reaction to go to completion; the pyrrolinecarboxylates 116а-n,q-s and acylpyrrolines 116o,p were obtained in good yields.…”