Organocatalytic Stereoselective Synthesis of Fluorinated 3,3′-Linked Bisoxindoles

Moskowitz, Max; Balaraman, Kaluvu; Wolf, Christian

doi:10.1021/acs.joc.7b03084

Cited by 27 publications

(10 citation statements)

References 47 publications

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“…Having established a profound interest in organofluorine chemistry, 32 33 34 35 36 37 38 39 40 including C–F bond activation methodology and synthetic or chiroptical sensing applications thereof, 19,21 , 41–43 we decided to investigate the possibility of practical alkyl fluoride to iodide conversion, which would also enable subsequent nucleophilic displacements or other reactions. Hilmersson and co-workers showed that this is possible with YbI 3 (THF) 3 , which has to be prepared from expensive ytterbium(II) iodide (Scheme 1 ).…”

Section: Table 1 Optimization Of the Csp ...mentioning

confidence: 99%

Selective Csp3–F Bond Functionalization with Lithium Iodide

Wolf¹,

Balaraman²,

Kyriazakos³

et al. 2022

Synthesis

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A highly efficient method for C–F bond functionalization of a broad variety of activated and unactivated aliphatic substrates with inexpensive lithium iodide is presented. Primary, secondary, tertiary, benzylic, propargylic and α-functionalized alkyl fluorides react in chlorinated or aromatic solvents at room temperature or upon heating to give the corresponding iodides, which are isolated in 91–99% yield. The reaction is selective for aliphatic monofluorides and can be coupled with in situ nucleophilic iodide replacements to install carbon–carbon, carbon–nitrogen, and carbon–sulfur bonds with high yields. Alkyl difluorides, trifluorides, even in activated benzylic positions, are inert under the same conditions and aryl fluoride bonds are also tolerated.

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Section: Table 1 Optimization Of the Csp ...mentioning

confidence: 99%

Selective Csp3–F Bond Functionalization with Lithium Iodide

Wolf¹,

Balaraman²,

Kyriazakos³

et al. 2022

Synthesis

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“…Based on our longstanding interest in fluorinated compounds, 7,9–20 we decided to screen a variety of chiral stationary phases (CSPs) to separate the enantiomers of the 2‐aryl‐2‐fluoroacetonitriles 1 – 10 by liquid chromatography, Figure 1. It was expected that the development of high performance liquid chromatography (HPLC) conditions that allow baseline separation of 1 – 10 would not be a simple task and most likely be achieved with some of the most frequently used CSPs originally introduced by Pirkle and Okamoto who without a doubt have been the most influential inventors of broadly useful chiral HPLC columns 21–27 .…”

Section: Introductionmentioning

confidence: 99%

Enantioseparation and racemization of α‐aryl‐α‐fluoroacetonitriles

et al. 2021

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The 2‐Aryl‐2‐fluoroacetonitriles have garnered increasing interest as versatile building blocks in asymmetric synthesis. However, the configurational stability of these organofluorines is poorly understood and analytical methods that can be used to differentiate between their enantiomers remain underdeveloped. In this study, baseline high performance liquid chromatography (HPLC) enantioseparation of ten 2‐aryl‐2‐fluoroacetonitriles was achieved by screening frequently used chiral stationary phases. While Chiralcel OD, Chiralpak AD, and Chiralpak AS proved to be most broadly useful, preparative separation of the enantiomers of 2‐(2‐naphthyl)‐2‐fluoroacetonitrile was possible on Chiralcel OJ. This enabled racemization studies at various temperatures and in the presence of organic bases which showed that this compound is configurationally stable under neutral conditions upon heating to 130°C for 6 h but undergoes complete racemization within 10 h in the presence of stoichiometric amounts of a guanidine base at room temperature. The racemization is likely to proceed via formation of an achiral keteniminate intermediate and obeys reversible first‐order reaction kinetics with a half‐life time of 87.7 min in ethanolic hexanes at 23.2°C. Racemization is significantly slower and occurs with a half‐life time of 23.1 h at 22.4°C when the guanidine is replaced with a weaker amidine base.

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“…In this context, intense research efforts have been devoted to the construction of enantioenriched oxindoles that have a tertiary fluorinated stereogenic center at the 3-position . Two main strategies, the direct fluorination of 3-alkyl- and 3-aryloxindoles, and the use of 3-fluorooxindoles as the building blocks, , have emerged for their asymmetric syntheses. Recently, the asymmetric Mannich reaction of 3-fluorooxindoles has attracted great interest, and several papers have documented the use of such reactions on the syntheses of 3-fully substituted 3-fluorooxindoles, containing a chiral β-amine fragment (Scheme ).…”

Section: Introductionmentioning

confidence: 99%

Enantioselective Mannich Reactions of 3-Fluorooxindoles with Cyclic N-Sulfamidate Aldimines

Zhao

Chen

et al. 2019

J. Org. Chem.

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Both the 3-fluorooxindole and cyclic sulfamidate frameworks are important in medicinal chemistry owing to their associated biological activities. We report an approach accessing 3-fully substituted 3-fluorooxindoles, containing a benzo-fused sulfamidate subunit through highly enantioselective Mannich-type reactions between 3-fluorooxindoles and cyclic benzo-fused N-sulfamidate aldimines. These reactions are promoted by a commercially available cinchona alkaloid catalyst, accommodate a broad substrate scope, and deliver the desired products in a yield of up to 99% with an enantiomeric excess of up to 94%. A plausible reaction pathway is also presented.

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Organocatalytic Stereoselective Synthesis of Fluorinated 3,3′-Linked Bisoxindoles

Cited by 27 publications

References 47 publications

Selective Csp3–F Bond Functionalization with Lithium Iodide

Selective Csp3–F Bond Functionalization with Lithium Iodide

Enantioseparation and racemization of α‐aryl‐α‐fluoroacetonitriles

Enantioselective Mannich Reactions of 3-Fluorooxindoles with Cyclic N-Sulfamidate Aldimines

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