NMR Enantiodiscrimination Phenomena by Quinine C⁹‐Carbamates

Abstract

Several C9‐carbamoyl derivatives of quinine have been prepared and compared as chiral solvating agents in NMR enantiodiscrimination experiments of amino acid derivatives. The origin of the enantiodiscrimination phenomena was identified by NMR conformational analysis of the chiral auxiliaries and investigations of solution complexation phenomena.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Mono‐ and bis‐quinidine organocatalysts in the asymmetric methanolysis of cis‐1,2,3,6‐tetrahydrophthalic anhydride: A conformational and mechanistic NMR study

“…This fact was clearly indicative of a chiral recognition phenomenon, probably related to the ability of the Cinchona alkaloid derivatives to act as NMR chiral solvating agents toward suitable chiral substances. [41][42][43][44][45][46][54][55][56] Control experiments with rac-16 (50 mM) and either 4 or 13 (5 mM) in toluene-d 8 , confirmed this hypothesis, showing that even such a small concentration of the alkaloid derivatives was sufficient for inducing a rather large anisochrony in most of the protons of the enantiomers of 16 (e.g., Dd 5 0.011 ppm for the methoxy groups of rac-16 in the presence of 13, Fig. 8a).…”

Zwitterionic Phosphorylated Quinines as Chiral Solvating Agents for NMR Spectroscopy

“…The phosphorylation of quinine was carried out by substitution of either diethyl-, dibutyl-, or diphenyl chlorophosphate with the parent compound in the presence of potassium tert-butoxide according to a previously published procedure. 16,18,24,25 Each conformation exhibits a specific pattern of interproton contacts that are detected by NMR spectroscopy. 2).…”

“…28 The results for crystalline 1c (Fig. 16,29 The autoaggregation phenomena is important to consider because, in principle, a decrease in the availability of some functional groups of the chiral auxiliary results in the loss of its enantiodiscrimination potency. In addition, the H11-H12 distance (2.88 Å) is longer than the H11-H18' distance (2.29 Å).…”

“…Therefore, this natural alkaloid was successfully used for the enantiodiscrimination of acids , alcohols and hydroxyesters, 1-4 hemiacetals and acetals, 5 binaphthyl compounds and alkylarylcarbinols, 6,7 and amino-and hydroxyphosphonates. [10][11][12][13][14][15][16][17] In particular, C9-carbamoylated quinines revealed complementary enantiodiscriminating properties with respect to native quinine toward a range of chiral substrates, such as amines, acids, amides, and N-protected amino acids. For the application of quinine analogs as chiral solvating agents (CSA) for NMR spectroscopy, much attention has been focused on carbamoyl derivatives modified at the C9, C22, and C23 positions.…”

“…[8][9][10] The multifunctional nature of quinine enables modulation of its enantiodiscrimination potential by selective modifications. 11,12,16 Recently, we reported quinines phosphorylated at the C-9 hydroxyl (i.e., diphenyl and diethyl phosphate mixed triesters 1, Fig. [10][11][12][13][14][15][16][17] In particular, C9-carbamoylated quinines revealed complementary enantiodiscriminating properties with respect to native quinine toward a range of chiral substrates, such as amines, acids, amides, and N-protected amino acids.…”