Efficient construction of highly functionalized spiro[γ-butyrolactone-pyrrolidin-3,3′-oxindole] tricyclic skeletons via an organocatalytic 1,3-dipolar cycloaddition

Abstract

Highly functionalized spiro[γ-butyrolactone-pyrrolidin-3,3'-oxindole] tricyclic skeletons were delivered successfully with high optical purity using an effective yet simple procedure.

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

“…Since the first asymmetric version of synthesis of spirooxindole-pyrrolidine derivatives was realized by Gong et al, via chiral BINOL-derived phosphoric acids, to catalyze the 1,3-dipolar cycloaddition of azomethine ylides formed in situ with N-Ac 2-oxoindolin-3-ylidenes [9]. A relatively broad range of dipolarophiles (such as 2-oxoindolin-3-ylidenes [10][11][12][13][14][15], cyclopropylidene acetates [16], 2-alkylidenecycloketones [17,18], α-alkylidene succinimides [19], and 5-alkylidene thia(oxa)zolidine-2,4-diones [20]) have been applied in the azomethine ylides-involved 1,3-dipolar cycloaddition to construct structurally and stereochemically rich spirocyclic pyrrolidine derivatives in the past decade. In contrast, little attention has been paid to α-methylene-γ-butyrolactone as a key electron-deficient alkene in the asymmetric 1,3-dipolar cycloaddition to construct the highly substituted spirocyclic [butyrolactone-pyrrolidine] skeletons with multiple contiguous stereocenters, although such skeletons with the lactone moiety have important biological activities.…”

Efficient Synthesis of Fully Substituted Pyrrolidine-Fused 3-Spirooxindoles via 1,3-Dipolar Cycloaddition of Aziridine and 3-Ylideneoxindole

“…Various elegant studies have generated molecules with spirooxindole-pyrrolidine skeletons [38,39,40,41,42] using diverse reactions, including 1,3-dipolar cycloaddition [43,44,45,46,47,48,49,50,51,52], ring-enlargement [53,54,55], intramolecular Mannich reaction [56], rearrangement [57] and alkylation [58]. Nitrogen ylides have been used to synthesize spirooxindole-pyrrolidines via 1,3-dipolar addition; this process shows high reactivity, high yield, and excellent stereoselectivity (Scheme 1a [43,44,45,46,47] and Scheme 1b [48,49,50,51,52]). In this approach, two steps are required to modify the nitrogen by alkylation, acylation, or, under harsh conditions, arylation.…”

Recent advances in the catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides

“…94 The reaction between o-hydroxy aromatic aldimines and alkylidene azlactones catalyzed by the bifunctional thiourea 44 led to chromeno [4,3-b]pyrrolidine derivatives with excellent stereoselectivity under mild reaction conditions (Scheme 43). Wang and co-workers 95 reported the reaction of homoserine lactone derived aldimino esters with methyleneindolinone to afford highly functionalized tricyclic skeletons 45. Excellent levels of stereocontrol over the four contiguous stereocenters were achieved using a thiourea bifunctional organocatalyst 46 (Scheme 44).…”