An Organocatalytic [3+2] Cyclisation Strategy for the Highly Enantioselective Synthesis of Spirooxindoles

Voituriez, Arnaud; Pinto, Nathalie; Neel, Mathilde; Retailleau, Pascal; Marinetti, Angéla

doi:10.1002/chem.201001791

Cited by 198 publications

(64 citation statements)

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“…Later, the cinchona-based primary amine 363 organocascade catalysis was used to access a variety of complex highly optically pure spirocompounds 365 with four contiguous stereocenters when reacting with the cyclic dienones 362 and the 3-substituted oxindoles 359 (Scheme 105) [209]. Recently, a novel iminium-enamine tandem process was established to construct densely substituted spirocyclopentaneoxindole core units 367 from 3-substituted bifunctional oxindoles 366 and readily available α, β-unsaturated aldehydes 336 catalyzed by a chiral secondary amine 318 with excellent stereoselectivity (up to 99 % ee) (Scheme 106) [210].…”

Section: Spirocyclopentaneoxindoles Synthesismentioning

confidence: 98%

Molecular diversity of spirooxindoles. Synthesis and biological activity

et al. 2015

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Spirooxindoles are important synthetic targets possessing extended biological activity and drug discovery applications. This review focuses on the various strategies for the enantioselective synthesis of spirocyclic oxindoles relying on reports over the past decade and from earlier work. The spirooxindoles in this review are separated into three structural classes, and then further categorized into the method type from which the spirocycle is generated.

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Section: Spirocyclopentaneoxindoles Synthesismentioning

confidence: 98%

Molecular diversity of spirooxindoles. Synthesis and biological activity

et al. 2015

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“…[2i,4b,6] The method has been applied notably to the facile, stereoselective creation of spirocyclopentene oxindole moieties. [7] Also, phosphine-promoted [3 + 2] cyclizations on cyclic bis-arylidene ketones afforded unique spiranic scaffolds with good stereocontrol of up to five stereogenic centres. [4b,8] As a further step towards molecular complexity, we consider here the use of heterocyclic a,b-unsaturated ketones, such as 3,5-bis(arylidene)-4-piperidones 1, dihydropyranones 2, dihydrothiopyranones 3, and dihydrothiopyranone oxides 4, as substrates in [3 + 2] cyclization processes.…”

Section: Introductionmentioning

confidence: 99%

Heterocyclic Spiranes and Dispiranes via Enantioselective Phosphine‐Catalyzed [3+2] Annulations

et al. 2012

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The synthesis of highly functionalized heterocyclic spiranes has been carried out by [3 + 2] cyclizations between allenoates and enones, under phosphine catalysis. Excellent enantioselectivity levels (ees up to 99%) have been attained in Ferro-PHANE-promoted cyclizations of this class, leading to chiral sulfides with unprecedented spiranic structures. The corresponding sulfoxides have been obtained then via a subsequent, highly diastereoselective oxidation of the prostereogenic sulfur centre.

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“…[6] Nucleophilic catalysis employing chiral phosphines is an intensively explored research area in asymmetric catalysis. [7] For the construction of five-membered ring systems, phosphine-mediated [3+2] annulations represents one of the most efficient approaches.…”

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confidence: 99%

Highly Enantioselective [3+2] Annulation of Morita–Baylis–Hillman Adducts Mediated by L‐Threonine‐Derived Phosphines: Synthesis of 3‐Spirocyclopentene‐2‐oxindoles having Two Contiguous Quaternary Centers

et al. 2011

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Spirocyclic oxindoles [1] are the structural motifs frequently found in many natural products and biologically active molecules.[2] Among many spirooxindole cores, the 3,3'-pyrrolidinyl spirooxindole units are well known for their strong bioactivity profiles, thus synthetic studies toward this fused heterocyclic system have been pursued intensively. Oxindoles having spiral carbocyclic rings are also important substructures that are widely present in numerous bioactive natural products. In this context, 3-spirocyclopentane-2-oxindoles containing two adjacent quaternary centers are particularly striking structural motifs [3] (Scheme 1), and their efficient asymmetric constructions are formidable synthetic tasks.[4] To the best of our knowledge, there were only two catalytic asymmetric syntheses in the literature dealing with similar structural scaffolds. Trost and co-workers reported an enantioselective construction of spirocyclic oxindolic cyclopentanes by using a palladium-catalyzed [3+2] cycloaddition of trimethylenemethane.[5] Very recently, Marinetti et al. disclosed an organocatalytic asymmetric [3+2] cyclization between 3-alkylideneindolin-2-ones and allenes for the synthesis of spirooxindoles. [6] Nucleophilic catalysis employing chiral phosphines is an intensively explored research area in asymmetric catalysis. [7] For the construction of five-membered ring systems, phosphine-mediated [3+2] annulations represents one of the most efficient approaches.[8] As part of our research program toward the development of asymmetric synthetic methods catalyzed by amino-acid-based organocatalysts, [9] we recently focused on the development of novel chiral phosphines from amino acids. We showed that dipeptide-derived novel phosphines were powerful catalysts for the enantioselective allene-acrylate [3+2] cycloadditions.[8n] More recently, we also derived a series of phosphine sulfonamide bifunctional catalysts and demonstrated their effectiveness in the enantioselective aza-Morita-Baylis-Hillman (aza-MBH) reactions.[10] We envisioned that phosphine-mediated [3+2] cyclizations may be utilized to construct spirooxindole cores (Scheme 2). The electron-deficient alkene components necessary for the annulation reactions can be conveniently derived from isatins. Notably, such tetrasubstituted activated alkenes are unexplored substrates in the asymmetric [3+2] cyclization processes, and their successful elaboration in the cycloaddition reaction may create two contiguous quaternary centers. Allenes and alkynes are commonly employed as C 3 synthons in the annulation reactions, and in this context, employment of more readily available and versatile C 3 synthons in the annulations is certainly ideal. The MBH reaction is one of the most atom-economic reactions for the construction of densely functionalized products, [11] and the Scheme 1. Spirocyclicpentane oxindole structures having two contiguous quaternary centers.Scheme 2. Construction of 3-spirocyclopentene-2-oxindoles through phosphine-catalyzed [3+2] cycloadditions of MBH add...

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An Organocatalytic [3+2] Cyclisation Strategy for the Highly Enantioselective Synthesis of Spirooxindoles

Cited by 198 publications

References 47 publications

Molecular diversity of spirooxindoles. Synthesis and biological activity

Molecular diversity of spirooxindoles. Synthesis and biological activity

Heterocyclic Spiranes and Dispiranes via Enantioselective Phosphine‐Catalyzed [3+2] Annulations

Highly Enantioselective [3+2] Annulation of Morita–Baylis–Hillman Adducts Mediated by L‐Threonine‐Derived Phosphines: Synthesis of 3‐Spirocyclopentene‐2‐oxindoles having Two Contiguous Quaternary Centers

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