Nucleophilic Addition of Organometallic Reagents to Cinchona Alkaloids: Simple Access to Diverse Architectures

Hintermann, Lukas; Schmitz, Marco; Englert, Ulli

doi:10.1002/anie.200701341

Cited by 39 publications

(23 citation statements)

References 28 publications

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“…To overcome the poor reactivity issue of the benzamide alkaloid 2 , a convergent thionation strategy was investigated from the amine analogue of epi ‐cinchonidine 1 . Firstly, amine 1 was transformed into its isothiocyanate analogue and then subjected to phenyllithium (or Grignard reagent) to yield product 4 resulting from the addition of the organometallic reagent to the quinoline ring (Scheme , R = Ph) . From these results, access to thioamide 3 from amine 1 using a thioacylation appeared more efficient and flexible.…”

Section: Resultsmentioning

confidence: 99%

Thioamide‐Substituted Cinchona Alkaloids as Efficient Organocatalysts for Asymmetric Decarboxylative Reactions of MAHOs

et al. 2017

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A new class of thioamide‐substituted cinchona derivatives is reported. A convergent and practical approach was developed to insert the thioamide functional group onto the cinchonidine from readily available dithioesters. These organocatalysts were effective in asymmetric decarboxylative Mannich and protonation reactions of α‐amido‐substituted malonic acid half oxyesters (MAHOs), affording α,β‐ and α‐amino acid derivatives, respectively, in good yields and stereoselectivities.

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Section: Resultsmentioning

confidence: 99%

Thioamide‐Substituted Cinchona Alkaloids as Efficient Organocatalysts for Asymmetric Decarboxylative Reactions of MAHOs

et al. 2017

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“…Kinetics of the catalytic oxa‐Michael cyclization : The kinetic analysis of the model reaction 1 a → 2 a was performed in the less volatile solvent chlorobenzene with the more soluble catalyst 2′‐ n ‐butylcinchonine29 to ensure stable concentrations over extended reaction times. The reaction progress was analyzed by chiral HPLC.…”

Section: Resultsmentioning

confidence: 99%

Inner Workings of a Cinchona Alkaloid Catalyzed Oxa‐Michael Cyclization: Evidence for a Concerted Hydrogen‐Bond‐Network Mechanism

Hintermann

Ackerstaff

Boeck

2013

Chemistry A European J

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Cinchona alkaloids catalyze the oxa-Michael cyclization of 4-(2-hydroxyphenyl)-2-butenoates to benzo-2,3-dihydrofuran-2-yl acetates and related substrates in up to 99% yield and 91% ee (ee = enantiomeric excess). Catalyst and substrate variation studies reveal an important role of the alkaloid hydroxy group in the reaction mechanism, but not in the sense of a hydrogen-bonding activation of the carbonyl group of the substrate as assumed by the Hiemstra-Wynberg mechanism of bifunctional catalysis. Deuterium labeling at C-2 of the substrate shows that addition of RO-H to the alkenoate occurs with syn diastereoselectivity of ≥99:1, suggesting a mechanism-based specificity. A concerted hydrogen-bond network mechanism is proposed, in which the alkaloid hydroxy group acts as a general acid in the protonation of the α-carbanionic center of the product enolate. The importance of concerted hydrogen-bond network mechanisms in organocatalytic reactions is discussed. The relative stereochemistry of protonation is proposed as analytical tool for detecting concerted addition mechanisms, as opposed to ionic 1,4-additions.

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“…However, this reaction resulted in butylation at the C2¢ atom only to give 4 (Scheme 1), analogous to the reaction of native quinine. 8 The 1 H NMR spectrum of phenol 3c, in which the hydroxy group is in the 2-position, showed two sets of signals that exhibited coalescence at 40 °C (DG ‡ ~14.5 kcal/mol).…”

Section: Figurementioning

confidence: 99%

New Functional Derivatives of 9-Phenylquinine

Boratyński¹,

Skarżewski²

2009

Synthesis

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Nucleophilic Addition of Organometallic Reagents to Cinchona Alkaloids: Simple Access to Diverse Architectures

Cited by 39 publications

References 28 publications

Thioamide‐Substituted Cinchona Alkaloids as Efficient Organocatalysts for Asymmetric Decarboxylative Reactions of MAHOs

Thioamide‐Substituted Cinchona Alkaloids as Efficient Organocatalysts for Asymmetric Decarboxylative Reactions of MAHOs

Inner Workings of a Cinchona Alkaloid Catalyzed Oxa‐Michael Cyclization: Evidence for a Concerted Hydrogen‐Bond‐Network Mechanism

New Functional Derivatives of 9-Phenylquinine

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