Endo-Selective Construction of Spiro-[butyrolactone-pyrrolidine] via Ag(I)/CAAA-Amidphos-Catalyzed 1,3-Dipolar Cycloaddition between Azomethine Ylides and α-Methylene-γ-Butyrolactone

Abstract

Construction of spirocyclic pyrrolidines bearing a spiro quaternary stereocenter is an enormous challenge in synthetic organic chemistry. In this report, we introduce a Ag(I)/CAAA-amidphos-catalyzed enantioselective 1,3-dipolar cycloaddition between azomethine ylides and α-methylene-γ-butyrolactone as an effective strategy for the construction of excellent endo-selective spiro-[butyrolactone-pyrrolidine] derivatives. Meanwhile, the catalytic system was also successfully applied in the three-component one-pot reaction of azomethine ylides formed in situ under the action of N,N′-diisopropylcarbodiimide serving as a dehydrator. Under the optimal conditions, endo-pyrrolidine derivatives bearing a spiro quaternary stereocenter were obtained with high to excellent yields (up to 95% yield) and enantioselectivities (up to 93% ee).

Recent Developments in Enantioselective Domino Reactions. Part A: Noble Metal Catalysts

“…Later in 2020, Wang et al described the first use of α-methylene-γ-butyrolactone 210 as dipolarophile in enantioselective silver-catalyzed formal [3 + 2] cycloadditions with azomethine ylides (Scheme 57). [67] Using a chiral silver catalyst derived from 2 mol% of Ag 2 O and 4 mol% of chiral cinchona alkaloid-derived amidophosphane ligand 211, glycine imino esters 191 underwent at À 20 °C enantioselective silver-catalyzed domino Michael/Mannich reaction with α-methyleneγ-butyrolactone 210 in toluene as solvent in the presence of H 2 O as an additive. The process afforded the corresponding chiral spirocyclic pyrrolidines 212 exhibiting three stereocenters as single endo-diastereomers in both uniformly high yields (78-94%) and enantioselectivities (75-93% ee).…”

Multifunctional Ag(I)/CAAA-Amidphos Complex-Catalyzed Asymmetric [3 + 2] Cycloaddition of α-Substituted Acrylamides

“…Many synthetic strategies have been devised in recent years, and among those strategies, transition-metal-catalyzed iminoesters-involved asymmetric [3 + 2] cycloaddition with various electron-deficient alkenes is considered to be one of the most efficient approaches for the construction of structurally diverse 4,4-disubstituted pyrrolidines . Nevertheless, it is noteworthy that dipolarophiles employed in these reactions are mainly highly reactive cyclic and acyclic enones and enesters (such as α-methylene-γ-butyrolactones, 2-alkylidenecycloketones, α-substituted α,β-unsaturated ketones or esters, alkylidene malonates, etc.) and cyclic lactams and diimides with a conformationally stable framework in the cycloaddition process (such as 2-oxoindolin-3-ylidenes, α-alkylidene succinimide, 5-alkylidene thia­(oxa)­zolidine-2,4-diones, etc.).…”