Chiral Silver Amides as Effective Catalysts for Enantioselective [3+2] Cycloaddition Reactions

Abstract

Asymmetric [3+2] cycloaddition of α-aminoester Schiff bases with substituted olefins is one of the most efficient methods for the preparation of chiral pyrrolidine derivatives in optically pure form. In spite of its potential utility, applicable substrates for this method have been limited to Schiff bases that bear relatively acidic α-hydrogen atoms. Here we report a chiral silver amide complex for asymmetric [3+2] cycloaddition reactions. A silver complex prepared from silver bis(trimethylsilyl)amide (AgHMDS) and (R)-DTBM-SEGPHOS worked well in asymmetric [3+2] cycloaddition reactions of α-aminoester Schiff bases with several olefins to afford the corresponding pyrrolidine derivatives in high yields with remarkable exo- and enantioselectivities. Furthermore, α-aminophosphonate Schiff bases, which have less acidic α-hydrogen atoms, also reacted with olefins with high exo- and enantioselectivities. The stereoselectivities of the [3+2] cycloadditions with maleate and fumarate suggested that the reaction proceeded by means of a concerted mechanism. An NMR spectroscopic study indicated that complexation of AgHMDS with the bisphosphine ligand was not complete, and that free AgHMDS, which did not show any significant catalytic activity, existed in the catalyst solution. This means that significant ligand acceleration occurred in the current reaction system.

Asymmetric Synthesis of Chiral Amino Carboxylic‐Phosphonic Acid Derivatives

“…In this context, Kobayashi et al . made significant progress in catalytic asymmetric preparation of chiral proline phosphonic analogues (Scheme 46a) [99,100] . α‐Iminophosphonates were engaged into [3+2] cycloaddition reaction with acrylates catalyzed by an in‐situ formed chiral silver‐amide complex.…”

Synthesis of Novel 2-(Het)arylpyrrolidine Derivatives and Evaluation of Their Anticancer and Anti-Biofilm Activity

“…The second approach is based on the formation of a pyrrolidine ring from acyclic precursors. Within this approach, the intermolecular [3+2] dipolar cycloaddition of activated alkenes to azomethine ylides plays a significant role [32,33,34,35,36,37]. Essential drawbacks of the abovementioned approaches are the need of expensive metal catalysts and/or harsh reaction conditions, as well as the need of the preliminary synthesis of starting compounds with appropriate functional groups and desired fragments.…”

Acid‐Catalyzed Intramolecular Imination / Nucleophilic Trapping of 4‐Aminobutanal Derivatives: One‐Pot Access to 2‐(Pyrazolyl)pyrrolidines

“…The second approach to the 2‐(hetaryl)pyrrolidines is based on the formation of pyrrolidine ring from acyclic precursors. Within this approach, the intermolecular [3+2] dipolar cycloaddition of activated alkenes to azomethine ylides plays a significant role . The activation of alkene double bond is achieved by introducing an electron‐withdrawing substituent – a carboxyl, carbonyl, or nitro group, in fewer cases – a cyano or trifluoromethyl group .…”