Copper-Catalyzed Asymmetric 1,3-Dipolar Cycloaddition of Imino Esters to Unsaturated Sultones

Abstract

The asymmetric 1,3-dipolar cycloaddition of glycine imino esters to 1-propene-1,3-sultone or sulfocoumarins is described. The reaction was efficiently catalyzed by Cu­(MeCN)4BF4/DTBM-Segphos or Cu­(MeCN)4BF4/tBu-FcPhox at room temperature to afford fused pyrrolidines as single regioisomers with excellent diastereoselectivity and enantioselectivity. The broad substrate scope of this reaction provides convenient access to structurally diverse multisubstituted pyrrolidines in an optically pure fashion.

Catalytic Enantioselective [3+2] Cycloaddition of N‐Metalated Azomethine Ylides

“…The Cu‐catalyzed exo ‐selective [3+2] cycloaddition of azomethine ylide 1 with unsaturated sultones 29 was described by Kanemoto and Fukuzawa and co‐workers [31] . Bisphosphine ligand DTBM‐Segphos L1 a proved to be a better ligand for the cycloaddition of 1‐propene‐1,3‐sultone with imino esters.…”

“…The Cu-catalyzed exo-selective [3 + 2] cycloaddition of azomethine ylide 1 with unsaturated sultones 29 was described by Kanemoto and Fukuzawa and co-workers. [31] Bisphosphine ligand DTBM-Segphos L1 a proved to be a better ligand for the cycloaddition of 1-propene-1,3-sultone with imino esters. Various glycine imino esters were tolerated under these conditions to deliver the products 30 in high yield and selectivity (Scheme 18).…”

Recent Advances in Nonprecious Metal Catalysis

“…The authors note that this methodology was used to prepare >1600 analogues for the cystic fibrosis program at AbbVie and was ultimately used to prepare ABBV/GLPG-3221 on an approximately 20 kg scale . In a related work, the Cu-catalyzed 1,3-dipolar cycloaddition of glycine imino esters to sulfocoumarins was used to prepare sultone-fused pyrrolidines with high enantio- and diastereoselectivity with Cu­(MeCN) 4 BF 4 (5 mol %) and ( S )-DTBM-Segphos (6 mol %) as the catalyst …”

N‐Terminal‐Specific Dual Modification of Peptides through Copper‐Catalyzed [3+2] Cycloaddition

“…This is achieved through the implementation of a copper-catalyzed three-component [3+2] cycloaddition reaction involving aldehydes and maleimides, leading to the formation of robust CÀ C bonds (Figure 1C). This approach capitalizes on the exclusive and efficient generation of metalated azomethine ylides, [12][13][14][15] a pivotal catalytic intermediate for the cycloaddition process, from the imine formed at the Nterminus even in the presence of various functional groups from the peptide itself as well as from the aldehyde and the maleimide. As a testament to the versatility and robustness of this design strategy, our method facilitates the precise and efficient modification of the N-termini of various oligo-and polypeptides, accommodating sequences containing up to 26 amino acid residues and multiple lysine moieties.…”