Solid‐Phase Conversion of Four Stereoisomers into a Single Enantiomer

Engwerda, Anthonius H. J.; Mertens, Johannes C. J.; Tinnemans, Paul; Meekes, Hugo; Rutjes, Floris P. J. T.; Vlieg, Elias

doi:10.1002/anie.201808913

Cited by 21 publications

(25 citation statements)

References 35 publications

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“…The above cited work inspired a group of Rutjes and Vlieg to probe into more complex 3,4-diarylsuccinimides 51 a, b, which bear two similar but different substituents at C3 and C4 (Scheme 21A). [70] Epimerization studies in CDCl 3 solution containing 5 mol% DBU revealed that under equilibrium cis-51 a was present in only 2%, ergo trans-51 a was more stable by 2.5 kcal.mol À 1 . In other words, the driving force of crystallization was not required in order to transform cis-51 a to its trans counterpart in this case.…”

Section: Reviews Ascwiley-vchdementioning

confidence: 99%

State of the Art in Crystallization‐Induced Diastereomer Transformations

Kolarovič

Jakubec

2021

Adv Synth Catal

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Crystallization-induced diastereomer transformations (CIDT) enable isolation of the target compounds in high enantio-and diastereomeric purities and with up to quantitative yields simply by filtration. Numerous inspiring examples of this appealing synthetic strategy reported over the last fifteen years are reviewed. Important observations along with aspects to consider when designing CIDT experiments are discussed. 3.3. Formation of Schiff Base or Related Intermediates 3.4. Aza-Michael and Mannich-Type Reactions 3.5. Strecker Reaction 3.6. Aldol Reactions 3.7. Epimerization at Phosphorus-Based Stereocenters 3.8. Racemization/Epimerization through Change of Conformation 3.9. Miscellaneous Examples of CIDT 4.Conclusions and Perspectives

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Section: Reviews Ascwiley-vchdementioning

confidence: 99%

State of the Art in Crystallization‐Induced Diastereomer Transformations

Kolarovič

Jakubec

2021

Adv Synth Catal

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“…On the other hand, and irrespective of actual mechanism of racemization, limitations by poorly performing (or even achiral) catalysts in enantioselective asymmetric synthesis, starting from achiral precursors, could be overcome by combination with Viedma ripening in analogy to asymmetric autocatalysis in homogenous systems. [17,35e,41] Analogously, application to diastereoselective asymmetric synthesis would also be possible, required that epimerization of individual chiral centers is selectively controlled, [42] extending the conglomerate concept to diastereomorphs or "quasi-enantiomorphs" (e. g. RÀ S and RÀ R), and when these neither differ too much in solubility nor their monomers' relative stability in a given solvent, in order to allow Viedma ripening. As the more stable diastereomer is likely to be the less soluble one, these could be conflicting goals, probably hard to reconcile in practice.…”

Section: Discussionmentioning

confidence: 99%

Speeding up Viedma Deracemization through Water‐catalyzed and Reactant Self‐catalyzed Racemization

et al. 2020

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Viedma deracemization is based on solution phase racemization, dissolution of racemic or scalemic conglomerates and crystal growth through autocatalytic cluster formation. With rate limiting racemization, its acceleration by appropriate catalysts may result in speeding up deracemization. A conglomerate‐forming chiral compound may principally racemize directly, or via reverse of its formation reaction. For a hydrazine derivative, we investigated available racemization pathways in presence of pyrrolidine or thiourea amine as base catalysts: via Mannich or aza‐Michael reaction steps and their reverse, or by enolization. Racemization by enolization was computationally found to dominate, both under water‐free conditions and in presence of water, involving a multitude of different pathways. Faster racemization in presence of water resulted indeed in more rapid deracemization, when the base was pyrrolidine. Under water‐free conditions, the role of water as enolization catalyst is assumed by chiral hydrazine itself – in autocatalytic racemization and in which both reactant and product are catalysts.

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“…One option is to conduct the deracemization in pure isopropanol (instead of the 1:1 mixture with heptane), thereby increasing the solubility, which is beneficial for the racemization rate (Figure ). In addition, more severe grinding, the use of temperature cycling, the application of chiral additives, or combinations of these are possibilities to speed up deracemization.…”

Section: Figurementioning

confidence: 99%

Racemization and Deracemization through Intermolecular Redox Behaviour

Engwerda¹,

Meekes²,

Bickelhaupt³

et al. 2019

Chemistry A European J

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Chiral molecules exhibiting a quinone and/or hydroquinone moiety are ubiquitous in natural products and small molecule drugs. Herein, we describe a chiral quinone‐hydroquinone molecule that racemizes through a reversible redox reaction. Using a combined computational and experimental approach, we show that this racemization proceeds via an intermolecular reaction mechanism. Starting from two achiral reactants, this molecule could be obtained in enantiopure form using Viedma ripening.

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Solid‐Phase Conversion of Four Stereoisomers into a Single Enantiomer

Cited by 21 publications

References 35 publications

State of the Art in Crystallization‐Induced Diastereomer Transformations

State of the Art in Crystallization‐Induced Diastereomer Transformations

Speeding up Viedma Deracemization through Water‐catalyzed and Reactant Self‐catalyzed Racemization

Racemization and Deracemization through Intermolecular Redox Behaviour

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