Quasienantiomers and Quasiracemates: New Tools for Identification, Analysis, Separation, and Synthesis of Enantiomers

Zhang, Qisheng; Curran, Dennis P.

doi:10.1002/chem.200500076

Cited by 105 publications

(68 citation statements)

References 68 publications

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“…[17] Usually the reagent or the catalyst are fully resolved. The use of enantio-impure reagents [18,19] or catalysts [20][21][22][23] in kinetic resolution has been discussed. The key factor for a high ee for the recovered starting material (ee sm ) is the size of the stereoselectivity factors.…”

Section: Introductionmentioning

confidence: 99%

“…[18,19] The kinetic resolution of a racemic or enantioenriched mixture involves a chiral reagent or catalyst. [17] Usually the reagent or the catalyst are fully resolved.…”

Section: Introductionmentioning

confidence: 99%

“…When 1.0 equiv of acylating agent (1S,2S)-2 (1.5 % ee) was treated with 0.93 equiv of racemic amine 3 and kept until the complete consumption of rac-3 (for example, 93 % conversion of 2), the remaining unreacted acylating agent (1S,2S)-2 was isolated with 15.5 % ee. The evaluation of the asymmetric amplification was conveniently done by isolation of 2 by flash chromatography and chiral HPLC or by hydrolysis of 2 into 1, the ee of which was measured by 19 F NMR in presence of quinidine. The results of Tables 1 and 2 confirm that a racemic reagent can easily enhance the ee of its partner if the stereoselectivity factor is not too small.…”

Section: Introductionmentioning

confidence: 99%

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Asymmetric Amplification by Kinetic Resolution Using A Racemic Reagent: Example in Amine Acetylation

Satyanarayana

Kagan

2006

Chemistry A European J

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The reaction of a racemic reagent on a mixture of enantiomers with small ee (ee=enantiomeric excess) has been studied for amine acylation. A substantial asymmetric amplification could be realized, for example, from 67 to >95.5 ee. The combination of asymmetric amplifications is subsequently discussed. Two sequential asymmetric amplifications, one using a racemic reagent and another using a positive nonlinear effect allowed us to start from 1.5 % ee and end with a large amount of a product of 97 % ee.

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Section: Introductionmentioning

confidence: 99%

“…[18,19] The kinetic resolution of a racemic or enantioenriched mixture involves a chiral reagent or catalyst. [17] Usually the reagent or the catalyst are fully resolved.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Asymmetric Amplification by Kinetic Resolution Using A Racemic Reagent: Example in Amine Acetylation

Satyanarayana

Kagan

2006

Chemistry A European J

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“…[1][2][3] In contrast to previously developed screening methods for enantioselective reactions which also make use of quasienantiomeric substrates, [4,5] our method relies on the quantification of catalytic intermediates rather than analysis of the product.…”

mentioning

confidence: 97%

Mass Spectrometric Screening of Chiral Catalysts by Monitoring the Back Reaction of Quasienantiomeric Products: Palladium‐Catalyzed Allylic Substitution

Müller¹,

Pfaltz²

2008

Angew Chem Int Ed

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The enantioselectivity of a chiral catalyst is usually determined by measuring the enantiomeric excess of the reaction product. However, the ee value obtained from analysis of the product does not necessarily reflect the intrinsic enantioselectivity of the catalyst. A competing noncatalytic background reaction which produces a racemic product, catalytically active impurities, or dissociation of a chiral ligand from a metal catalyst can lead to low enantiomeric purity even though the catalyst itself is highly selective.We recently reported a method for determining the intrinsic enantioselectivity of chiral catalysts by using quasienantiomeric substrates and electrospray ionization mass spectrometry (ESI-MS) as the analytical tool. [1][2][3] In contrast to previously developed screening methods for enantioselective reactions which also make use of quasienantiomeric substrates, [4,5] our method relies on the quantification of catalytic intermediates rather than analysis of the product.As a first application, we studied the kinetic resolution of racemic allyl esters by using a palladium-catalyzed allylic substitution reaction (Scheme 1).[6] By starting with a 1:1 mixture of two mass-labeled, quasienantiomeric substrates (S)-4 a and (R)-4 b, the selectivity factor s = k a /k b of a catalyst can be deduced from the ratio of the corresponding allyl intermediates 5 a/5 b as determined by mass spectrometry (Scheme 2). As ESI-MS allows the selective detection of charged species in the presence of a large excess of neutral compounds, cationic intermediates such as 5 a and 5 b can be observed even at low catalyst loadings under conditions normally used for preparative catalytic reactions. The method is fast and reliable, does not require workup of the reaction mixture, and in contrast to methods based on product analysis allows the simultaneous screening of catalyst mixtures (if the catalysts have different molecular masses). The screening of a large number of catalysts showed that the selectivity of a catalyst in the kinetic resolution step did not correlate with the enantioselectivity of the nucleophilic addition to the allyl intermediate 2. It is this step that determines the enantioselectivity of the overall reaction leading from the racemic allyl ester 1 to the optically active substitution product 3 (Scheme 1). Many catalysts that gave high enantioselectivity in the overall reaction were inefficient in the kinetic resolution of allyl esters.Herein we report an extension of our screening method which allows the determination of the enantioselectivity in the nucleophilic addition step and can, therefore, be used to evaluate the intrinsic enantioselectivity of chiral catalysts for the overall allylic substitution process. Instead of screening the forward reaction, we monitored the back reaction of quasienantiomeric products that leads to the corresponding mass-labeled allyl-palladium complexes. According to the principle of microscopic reversibility, the transition states of Scheme 1. General mechanism of the palladium-ca...

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“…[1] These materials, termed quasiracemates, offer important evidence of the role of molecular shape in the construction of molecular assemblies [2] and have recently been utilized for their molecularrecognition behavior. [3] The first likely occurrence of quasiracemates in the literature dates back one hundred and sixty years to Pasteurs celebrated tartaric acid work. [4] In addition to providing extensive details of the recrystallization outcomes for tartaric acids, Pasteur described the formation of unusual compounds he referred to as "combination isomers".…”

mentioning

confidence: 99%

Rediscovering Pasteur's Quasiracemates

Wheeler¹,

Grove²,

Davis³

et al. 2007

Angew Chem Int Ed

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A fresh Pasteur: Reconstruction of Pasteur's 1853 account of peculiar three‐component crystals has confirmed the identities of the two crystalline phases as ammonium (+)‐bitartrate (central crystal) and a quasiracemate of ammonium (+)‐bitartrate/(−)‐bimalate (adjoining crystal laths). The quasiracemate contains approximately inversion‐related molecular assemblies in which each bitartrate and bimalate component forms a homomeric catemeric motif.

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Quasienantiomers and Quasiracemates: New Tools for Identification, Analysis, Separation, and Synthesis of Enantiomers

Cited by 105 publications

References 68 publications

Asymmetric Amplification by Kinetic Resolution Using A Racemic Reagent: Example in Amine Acetylation

Asymmetric Amplification by Kinetic Resolution Using A Racemic Reagent: Example in Amine Acetylation

Mass Spectrometric Screening of Chiral Catalysts by Monitoring the Back Reaction of Quasienantiomeric Products: Palladium‐Catalyzed Allylic Substitution

Rediscovering Pasteur's Quasiracemates

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