Facile and Convenient One-Pot Process for the Synthesis of Spirooxindole Derivatives in High Optical Purity Using (−)-(S)-Brevicolline as an Organocatalyst

Abstract

Abstract:The paper presents an application of the asymmetry approach to spirooxindoles via Brevicolline, Cinchonidine or Cinchonine catalyzed one-pot multicomponent synthesis. Brevicolline, in comparison with Cinchonidine or Cinchonine, catalyzes the reaction of isatins, acetylacetone/ethyl 3-oxobutanoate and malononitrile, with the formation of spiro [oxindole-3,4'-4'H-pirane] derivatives in an optically active form in very good to excellent yields.

New Organocatalytic Asymmetric Synthesis of Highly Substituted Chiral 2-Oxospiro-[indole-3,4′- (1′,4′-dihydropyridine)] Derivatives

“…Both groups used the same multicomponent strategy employing Et 3 N under reflux of EtOH (Scheme 1a). However, it is remarkable that Dabiri and Bazgir’s group obtained pyrano-fused spirooxindoles [37], instead of dihydropyridine-fused spirooxindoles, under very similar conditions [38,39].…”

Enantioselective Cascade Reaction of α‐Cyano Ketones and Isatylidene Malononitriles: Asymmetric Construction of Spiro[4H‐pyran‐oxindoles]

“…The reactions were performed with 2 mol-% of the catalyst and 1 mol-% of piperidine in CH 2 Cl 2 at 0°C, and the results are summarized in Table 1. We began by using chiral bifunctional tertiary amine-thiourea organocatalysts C1-C6, and to our delight, the cascade reaction afforded spiro product 3aa in excellent yields with moderate enantioselectivities (Table 1, Entries [1][2][3][4][5][6]. Cinchona-derived thioureas gave similar results, and the absolute configuration of the product was controlled by the chiral backbone of these catalysts (Table 1, .…”

“…[2] Spiro[4H-pyran-oxindole] derivatives, which belong to the spirooxindole family of compounds, have various biological activities such as anticancer, antifungal, and antibacterial properties. [4] Several research groups [5][6][7][8] then developed asymmetric tandem reactions for the synthesis of spiro[4H-pyran-oxindole] compounds. However, the enantioselective synthesis of spiro[4H-pyran-oxindole] derivatives is rarely described.…”

Recent Developments in Asymmetric Organocatalytic Domino Reactions

“…Then, Michael addition of 1,3-diketone 355 to 358 led to intermediates 359, in equilibrium with intermediates 360, which finally cyclized to afford products 357a-h. More recently, Macaev et al have investigated the reaction of isatine (R 1 = R 2 = H) with malononitrile 354 and acetylacetone catalyzed by brevicolline (10 mol% in CH 2 Cl 2 at 0 8C). [160] The corresponding spiro[4H-pyran-3,3'-oxindole] was formed in 62% yield and an enantioselectivity of 94% ee.…”