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

Abstract

Asymmetric [3 + 2] cycloaddition reactions are fascinating and powerful methods for the synthesis of enantioenriched pyrrolidines up to four stereocentres. Pyrrolidines are important compounds for both biology and organocatalytic applications. This review summarizes the most recent advances in the enantioselective synthesis of pyrrolidines by [3 + 2] cycloadditions of azomethine ylides using metal catalysis. It has been organized by the type of metal catalysis used and further arranged by the complexity nature of dipolarophile. The presentation of each reaction type highlights their advantages and limitations.

Annulations involving p-benzoquinones: stereoselective synthesis of fused, spiro and bridged molecules

“…Especially, asymmetric [3+2] cycloaddition is considered one of the trickiest approaches in synthetic organic chemistry. 57,58 In 2018, Wang and Tang realized the synthesis of optically pure benzofuroindolines 3 via the enantioselective [3+2] annulation of p -benzoquinone 1 with indoles 2 . 59 The transformation was carried out in dichloromethane with the aid of a BOX ligand copper( ii ) hydrate complex (Catalyst L1 ) and 4 Å molecular sieves.…”

Synthesis of Spirocyclic Pyrrolidine Compounds via Silver-Catalyzed Asymmetric [3 + 2] Cycloaddition Reaction of Imino Esters with α-Alkylidene Succinimides

“…Many efforts have been made for the development of synthetic methods, resulting in the fabrication of spirocyclic pyrrolidine scaffolds . Among them, the catalytic asymmetric [3 + 2] cycloaddition of azomethine ylides to a variety of ylidene-heterocycles has emerged as a robust synthetic tool for the synthesis of structurally and stereochemically diverse pyrrolidine derivatives, including spirocyclic pyrrolidines bearing chiral quaternary centers . Ylidene-heterocycles, such as 2-oxoindolin-3-ylidenes, 2-alkylidene-cycloketones, α-methylene-γ-butyrolactones, and α-alkylidene succinimides, are promising dipolarophiles, which react with azomethine ylides to generate chiral spirocyclic pyrrolidine skeletons.…”

Decarboxylative 1,3-dipolar cycloadditions of l-proline

“…Azomethine ylide intermediates generated in situ from the decarboxylative condensation of amino acids with isatins/ aldehydes act as 1,3-dipoles to react with various dipolarophiles via 1,3-DC reaction. [9][10][11][12] Azomethine ylides consist of two sp 2 carbon atoms and one nitrogen atom with a HOMO orbital that directly interacts with a LUMO orbital of a dipolarophile. These intermediates are the most efficient synthons in the construction of spiro-heterocycles, such as pyrrolizines, pyrrolizidines, and pyrazolidines.…”