Chiral NMR discrimination of pyrrolidines using (18-crown-6)-2,3,11,12-tetracarboxylic acid

Lovely, Ann E.; Wenzel, Thomas J.

doi:10.1016/j.tetasy.2006.10.002

Cited by 28 publications

(13 citation statements)

References 22 publications

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“…Unfortunately, we are not able to measure association constants of the substrates with 1 using common methods, because of the presence of neutralization and association processes in this system. 21 The diminishment in enantiomeric discrimination observed for the alkene resonances of 3 (Fig. 4) and Nmethyl and methine resonances of 2 (Fig.…”

Section: Resultsmentioning

confidence: 94%

“…22 Only in the case of a sterically hindered substrate such as 2,2,5,5-tetramethyl-3-pyrrolidine carboxylate, which has four substituent groups a to the nitrogen atom, was the enantiomerically discrimination negligibly small (0.018 ppm at a 2:1 crown-substrate ratio). 21 All other substrates had substantial enantiomeric nonequivalence in the 1 H and/or 13 C NMR spectra. Herein we report 1 H and 13 C NMR data for a series of aryl-containing secondary amines with 1 ( Fig.…”

Section: Analysis Of Aryl-containing Secondary Aminesmentioning

confidence: 96%

“…We have previously shown the utility of 1 as a chiral NMR solvating agent for pyrrolidines, 21 piperidines, and piperazines. 22 Only in the case of a sterically hindered substrate such as 2,2,5,5-tetramethyl-3-pyrrolidine carboxylate, which has four substituent groups a to the nitrogen atom, was the enantiomerically discrimination negligibly small (0.018 ppm at a 2:1 crown-substrate ratio).…”

Section: Analysis Of Aryl-containing Secondary Aminesmentioning

confidence: 99%

“…18,19 We recently showed that 1 is an effective chiral NMR solvating agent for secondary amines, especially pyrrolidines, piperidines, and piperazines. [20][21][22] In this report we extend the application of 1 to a series of secondary amines with aryl substituent groups. We further show that 1 can be used to distinguish prochiral nuclei in primary and secondary amines.…”

Section: Introductionmentioning

confidence: 96%

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Chiral NMR discrimination of amines: Analysis of secondary, tertiary, and prochiral amines using (18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid

Lovely

Wenzel

2007

Chirality

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Enantiomeric discrimination is observed in the 1H and 13C NMR spectra of secondary and tertiary amines in the presence of (-)-(18-crown-6)-2,3,11,12-tetracarboxylic acid (1). Nonequivalence of the resonances of prochiral nuclei in primary and secondary amines is also observed when they associate with 1. The amines are added in their neutral form and are protonated by the carboxylic acid groups of 1 to produce the corresponding ammonium and carboxylate ions. Secondary amines associate with 1 through two hydrogen bonds and an ion pair interaction. Tertiary amines can only form one hydrogen bond to accompany the ion pairing. Chiral discrimination in the 1H and 13C NMR spectra of a series of aryl-containing secondary amines is of sufficient magnitude to determine enantiomeric purities. The discrimination in the spectra of tertiary amines with 1 is smaller, but 13C NMR spectra provided enough distinction for the determination of enantiomeric purity.

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Section: Resultsmentioning

confidence: 94%

Section: Analysis Of Aryl-containing Secondary Aminesmentioning

confidence: 96%

Section: Analysis Of Aryl-containing Secondary Aminesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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Chiral NMR discrimination of amines: Analysis of secondary, tertiary, and prochiral amines using (18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid

Lovely

Wenzel

2007

Chirality

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“…A variety of reagents are available for NMR determination of the percentage of enantiomeric enrichment (%ee) as well as absolute stereochemistry, 379,380 and chiral solvents can be used with particular types of compounds for the determination of absolute stereochemistry by NMR. [381][382][383][384] …”

Section: Current Toolbox-nmr Approachesmentioning

confidence: 99%

Enantiomeric separation and determination of absolute stereochemistry of asymmetric molecules in drug discovery—Building chiral technology toolboxes

McConnell¹,

Bach

Balibar³

et al. 2007

Chirality

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The application of Chiral Technology, or the (extensive) use of techniques or tools for the determination of absolute stereochemistry and the enantiomeric or chiral separation of racemic small molecule potential lead compounds, has been critical to successfully discovering and developing chiral drugs in the pharmaceutical industry. This has been due to the rapid increase over the past 10-15 years in potential drug candidates containing one or more asymmetric centers. Based on the experiences of one pharmaceutical company, a summary of the establishment of a Chiral Technology toolbox, including the implementation of known tools as well as the design, development, and implementation of new Chiral Technology tools, is provided.

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Determination of Enantiomeric Purity and Absolute Configuration byNMRSpectroscopy

Wenzel

2013

Stereoselective Synthesis of Drugs and Natural Products

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Chiral NMR discrimination of pyrrolidines using (18-crown-6)-2,3,11,12-tetracarboxylic acid

Cited by 28 publications

References 22 publications

Chiral NMR discrimination of amines: Analysis of secondary, tertiary, and prochiral amines using (18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid

Chiral NMR discrimination of amines: Analysis of secondary, tertiary, and prochiral amines using (18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid

Enantiomeric separation and determination of absolute stereochemistry of asymmetric molecules in drug discovery—Building chiral technology toolboxes

Determination of Enantiomeric Purity and Absolute Configuration byNMRSpectroscopy

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