Racemization and Deracemization through Intermolecular Redox Behaviour

Engwerda, Anthonius H. J.; Meekes, Hugo; Bickelhaupt, F.; Rutjes, Floris P. J. T.; Vlieg, Elias

doi:10.1002/chem.201902438

Cited by 5 publications

(4 citation statements)

References 31 publications

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“…Most of the reported works are based on α-amino acid derivatives by converting them into imines, which then by tautomerization racemize the H atom bearing a stereogenic center (example of Figure ). However, other racemization procedures, through a redox reaction, thermal sigmatropic rearrangement, atropisomerism, and photoisomerization , are being reported. The efficiency of the deracemization and its compatibility in the Viedma procedure have been used for direct absolute asymmetric synthesis and one-pot procedures. ,, In summary, Viedma deracemization is on the way to become part of retrosynthetic analysis for absolute asymmetric synthesis. , Experimental reports improving the mechanical crystal attrition ,− or using other types of selective energy, for example, temperature gradients and temperature cycles, ,,− ultrasound, and photochemical catalysis .…”

Section: Chiral Polarization Forcesmentioning

confidence: 99%

“…203 Most of the reported works are based on α-amino acid derivatives by converting them into imines, 204 which then by tautomerization racemize the H atom bearing a stereogenic center (example of Figure 9). However, other racemization procedures, through a redox reaction, 205 thermal sigmatropic rearrangement, 206 atropisomerism, 207 and photoisomerization 208,209 are being reported. The efficiency of the deracemization and its compatibility in the Viedma procedure have been used for direct absolute asymmetric synthesis and one-pot procedures.…”

Section: Chiral Recognition and Chemical Enantioselective Transformat...mentioning

confidence: 99%

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Spontaneous Deracemizations

et al. 2021

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Spontaneous deracemizations is a challenging, multidisciplinary subject in current chirality research. In the absence of any chiral inductors, an achiral substance or a racemic composition is driven into an enantioenriched or even homochiral state through a selective energy input, e.g., chemical potential, photoirradiation, mechanical grinding, ultrasound waves, thermal gradients, etc. The most prominent examples of such transformations are the Soai reaction and the Viedma deracemization. In this review, we track the most recent developments in this topic and recall that many other deracemizations have been reported for solutions from mesophases to conglomerate crystallizations. A compiled set of simply available achiral organic, inorganic, organometallic, and MOF compounds, yielding conglomerate crystals, should give the impetus to realize new experiments on spontaneous deracemizations. Taking into account thermodynamic constraints, modeling efforts have shown that structural features alone are not sufficient to describe spontaneous deracemizations. As a guideline of this review, particular attention is paid to the physicochemical origin and symmetry requirements of such processes.

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Section: Chiral Polarization Forcesmentioning

confidence: 99%

Section: Chiral Recognition and Chemical Enantioselective Transformat...mentioning

confidence: 99%

Spontaneous Deracemizations

et al. 2021

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“…The other prerequisite, which further narrows the applicability of the two techniques, is that the model compounds racemize in solution: in this way the two enantiomers continuously interconvert into each other and the chiral amplification of the enantiomeric excess ( ee ) in the solids can take place . Despite these limitations, both processes have been proven successful for a wide number of compounds, including pharmaceuticals, coordination complexes and organometallic compounds. ,− In several examples in which both Viedma ripening and temperature cycling were applied to the same compound, the latter technique was shown to proceed with a higher rate . It was also evident that both processes display an exponential trend, − suggesting in both cases a self-amplification mechanism which has already been explained for the Viedma ripening process .…”

Section: Introductionmentioning

confidence: 99%

Combining Viedma Ripening and Temperature Cycling Deracemization

Belletti¹,

Schuurman²,

Stinesen³

et al. 2022

Crystal Growth & Design

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While much data are available for the Viedma ripening and temperature cycling deracemization processes, not much is known about the advantages (or disadvantages) of a combination of the two. We here try to elucidate what happens when Viedma ripening is used in combination with temperature cycling by comparing not only the deracemization times but also the change in the sizes of the crystals. We found that, in the case of NMPA ( rac -(2-methylbenzylidene)-phenylglycine amide) as a model compound, combined experiments significantly increase the deracemization time. By tuning the process parameters, it is possible to approach experimental conditions where both Viedma ripening and temperature cycling control the deracemization. Under those conditions, however, the deracemization time is not significantly improved. Following our results, it seems unlikely that a combination of Viedma ripening and temperature cycling would shorten the deracemization time. Nevertheless, these experiments might provide clues for unraveling the mechanism of temperature cycling.

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“…[20] Racemization methods compatible with crystallization have remained limited: base-catalyzed racemization remains the most commonly used for deracemization, [11b-d, 21] although application of photo-chemically and redox induced variants have been reported. [22] Consequently, the essential requirement to combine racemization and conglomerate crystallization under mutually compatible conditions has greatly limited the application potential.…”

Section: Angewandte Chemiementioning

confidence: 99%

Combining Incompatible Processes for Deracemization of a Praziquantel Derivative under Flow Conditions

Valenti

Tinnemans²,

Baglai

et al. 2021

Angewandte Chemie

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An efficient deracemization method for conversion of the racemate to the desirable (R)-enantiomer of Praziquantel has been developed by coupling incompatible racemization and crystallization processes. By a library approach, a derivative that crystallizes as a conglomerate has been identified. Racemization occurs via reversible hydrogenation over a palladium on carbon (Pd/C) packed column at 130 8C, whereas deracemization is achieved by alternating crystal growth/ dissolution steps with temperature cycling between 5-15 8C. These incompatible processes are combined by means of a flow system resulting in complete deracemization of the solid phase to the desired (R)-enantiomer (98 % ee). Such an unprecedented deracemization by a decoupled crystallization/racemization approach can readily be turned into a practical process and opens new opportunities for the development of essential enantiomerically pure building blocks that require harsh methods for racemization.

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Racemization and Deracemization through Intermolecular Redox Behaviour

Cited by 5 publications

References 31 publications

Spontaneous Deracemizations

Spontaneous Deracemizations

Combining Viedma Ripening and Temperature Cycling Deracemization

Combining Incompatible Processes for Deracemization of a Praziquantel Derivative under Flow Conditions

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