Diastereo- and enantioselective phase-transfer alkylation of 3-substituted oxindoles with racemic secondary alkyl halides

Ohmatsu, Kohsuke; Furukawa, Yukino; Kiyokawa, Mari; Ooi, Takashi

doi:10.1039/c7cc07122a

Cited by 23 publications

(9 citation statements)

References 113 publications

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“…Ring opening of the 2,2‐ disubstituted aziridines 132 occurs with inversion at the more‐substituted quaternary carbon to install a quaternary center. The chiral induction arises through the catalytic action of the 1,2,3‐triazolium salt 133 , though whether this occurs through interaction with the aziridine to create a chiral electrophile or via an association with the oxindole to form a chiral nucleophile is an open question …”

Section: Alkylations With Secondary Electrophilesmentioning

confidence: 99%

Diastereoselective Electrophile‐Directed Alkylations

2019

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Electrophile‐directed alkylations in which a chiral, sp3‐hybridized electrophile, dictates the facial attack on a prochiral nucleophile, provides a powerful method of asymmetric induction. The strategy is inherently efficient because the asymmetry of an sp3‐hybridized electrophile is propagated to install two contiguous chiral centers, the first through an SN2 displacement and the second through preferential facial recognition. The two primary modes of topological matching are through steric approach control and chelation between the electrophile and nucleophile. Electrophiles capable of chelation generally induce higher diastereoselectivity for secondary and primary electrophiles. Key parameters that influence the stereoselectivity are those expected for enolate/anion alkylations: solvent, cation, complexing agents. A generalized enolate‐electrophile alkylation model is used to provide an evaluative framework for collecting related alkylations with the aim of providing insight into the origin of the electrophile‐directed diastereoselectivity as a powerful synthetic strategy.

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Section: Alkylations With Secondary Electrophilesmentioning

confidence: 99%

Diastereoselective Electrophile‐Directed Alkylations

2019

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“…This secondary association would rigidify the otherwise flexible conformation of the acyclic enolate, which would be beneficial for dictating the relative stereochemistry of the subsequent alkylation event with hitherto unattainable precision (Figure C). Here, we report the highly enantio- and diastereoselective cyanoalkylation of trisubstituted electron-deficient olefins with potassium cyanide and alkyl halides, which relies on the use of chiral 1,2,3-triazoluim ions as catalysts featuring prominent hydrogen-bond-donating and anion-binding capabilities. , This method provides a straightforward route to highly functionalized chiral molecular entities possessing contiguous all-carbon quaternary and tertiary stereocenters from readily available compounds.…”

Section: Introductionmentioning

confidence: 99%

“…Here, we report the highly enantio-and diastereoselective cyanoalkylation of trisubstituted electron-deficient olefins with potassium cyanide and alkyl halides, which relies on the use of chiral 1,2,3-triazoluim ions as catalysts featuring prominent hydrogen-bond-donating and anion-binding capabilities. 37,38 This method provides a straightforward route to highly functionalized chiral molecular entities possessing contiguous allcarbon quaternary and tertiary stereocenters from readily available compounds.…”

Section: ■ Introductionmentioning

confidence: 99%

Catalytic Asymmetric Cyanoalkylation of Electron-Deficient Olefins with Potassium Cyanide and Alkyl Halides

et al. 2021

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The stereoselective cyanoalkylation of electron-deficient olefins with potassium cyanide and alkyl halides was developed based on the utilization of modular chiral 1,2,3-triazolium salts featuring a hydrogen bond-donor ability as catalysts. The reaction involving multiple carbon−carbon bond formations proceeds via the enantioselective conjugate addition of a cyanide ion and the consecutive catalyst-controlled diastereoselective alkylation of intermediary chiral triazolium enolates. Control experiments revealed that the use of a properly tuned chiral triazolium ion as a catalyst and the presence of the cyano functionality in the intermediary enolate are of crucial importance for achieving high levels of acyclic absolute and relative stereocontrol. Article pubs.acs.org/JACS

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“…In this context, we realised that phase-transfer catalysis, due to its operational simplicity and utility in mediating reactions involving charged intermediates, could be an excellent methodology for the enantioselective S N 2 alkylation of enolates derived from the 2-oxindole core [13][14][15][16][17][18][19][20][21][22][23]. In recent years, several examples regarding the alkylation of 3-subsituted-2-oxindoles, via asymmetric phase-transfer catalysis, have been reported [24][25][26][27][28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

Litvajova¹,

Sorrentino²,

Twamley³

et al. 2021

Beilstein J. Org. Chem.

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N-Protected oxindole derivatives of unprecedented malleability bearing ester moieties at C-3 have been shown to participate in enantioselective phase-transfer-catalysed alkylations promoted by ad-hoc designed quaternary ammonium salts derived from quinine bearing hydrogen-bond donating substituents. For the first time in such phase-transfer-catalysed enolate alkylations, the reactions were carried out under base-free conditions. It was found that urea-based catalysts outperformed squaramide derivatives, and that the installation of a chlorine atom adjacent to the catalyst’s quinoline moiety aided in avoiding selectivity-reducing complications related to the production of HBr in these processes. The influence of steric and electronic factors from both the perspective of the nucleophile and electrophile were investigated and levels of enantiocontrol up to 90% ee obtained. The synthetic utility of the methodology was demonstrated via the concise enantioselective synthesis of a potent CRTH2 receptor antagonist.

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Diastereo- and enantioselective phase-transfer alkylation of 3-substituted oxindoles with racemic secondary alkyl halides

Cited by 23 publications

References 113 publications

Diastereoselective Electrophile‐Directed Alkylations

Diastereoselective Electrophile‐Directed Alkylations

Catalytic Asymmetric Cyanoalkylation of Electron-Deficient Olefins with Potassium Cyanide and Alkyl Halides

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

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Diastereo- and enantioselective phase-transfer alkylation of 3-substituted oxindoles with racemic secondary alkyl halides

Cited by 23 publications

References 113 publications

Diastereoselective Electrophile‐Directed Alkylations

Diastereoselective Electrophile‐Directed Alkylations

Catalytic Asymmetric Cyanoalkylation of Electron-Deficient Olefins with Potassium Cyanide and Alkyl Halides

Base-free enantioselective SN2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

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Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis