Conformational Analysis of MαNP Esters, Powerful Chiral Resolution and <sup>1</sup>H NMR Anisotropy Tools – Aromatic Geometry and Solvent Effects on Δ<i>δ</i> Values

Kasai, Yusuke; Sugio, Akinori; Sekiguchi, Satoshi; Kuwahara, Shunsuke; Matsumoto, Takatoshi; Watanabe, Masataka; Ichikawa, Akio; Harada, Nobuyuki

doi:10.1002/ejoc.200600856

Cited by 43 publications

(29 citation statements)

References 55 publications

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“…between the CDA-and the substrate-part can be assigned unambiguously. Mosher acid esters or amides 24,[62][63][64][65] with the anisotropic phenyl group is quite reliable in that sense; Harada's MaNP esters 66,67 seems to be even better. The majority of practical application is focussed on the discrimination of enantiomers by CSAs for the determination of enantiomeric excess (e.e.).…”

Section: Resultsmentioning

confidence: 99%

Chiral recognition of ethers by NMR spectroscopy

Duddeck

Gómez

2008

Chirality

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Enantiomers of chiral ethers and acetals are notoriously difficult to differentiate because their reactivity is low and they are poor donors to any Lewis acid or metal ion. As an exception, epoxides are somewhat better donors. This review describes the properties of ethers, explains NMR methods for their chiral recognition and describes successful examples of ether differentiation. The majority of literature reports deals with chiral lanthanide shift reagents and dirhodium tetracarboxylate complexes, which were used as enantiopure auxiliaries to create diastereomeric adducts with dispersed (1)H and (13)C NMR signals. The various methods are compared as to which is best suited for which purpose.

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Section: Resultsmentioning

confidence: 99%

Chiral recognition of ethers by NMR spectroscopy

Duddeck

Gómez

2008

Chirality

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“…A solution to the difficulty mentioned above was found through the use of 2-methoxy-2-(1-naphthyl)propionic acid (MαNP), which had been used in determining the absolute configuration of chiral secondary alcohols (33,34). The naphthyl ring of MαNP esters exerts greater anisotropic shielding effects on substituents than phenyl group.…”

Section: S)-3b Was Also Used As a Key Intermediate In The Synthesis Omentioning

confidence: 99%

Highly enantioselective synthesis of γ-, δ-, and ε-chiral 1-alkanols via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA)–Cu- or Pd-catalyzed cross-coupling

Oda

Kamada

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Despite recent advances of asymmetric synthesis, the preparation of enantiomerically pure (≥99% ee) compounds remains a challenge in modern organic chemistry. We report here a strategy for a highly enantioselective (≥99% ee) and catalytic synthesis of various γ-and more-remotely chiral alcohols from terminal alkenes via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA reaction)-Cu-or Pd-catalyzed cross-coupling. ZACA-in situ oxidation of tert-butyldimethylsilyl (TBS)-protected ω-alkene-1-ols produced both (R)-and (S)-α,ω-dioxyfunctional intermediates (3) in 80-88% ee, which were readily purified to the ≥99% ee level by lipase-catalyzed acetylation through exploitation of their high selectivity factors. These α,ω-dioxyfunctional intermediates serve as versatile synthons for the construction of various chiral compounds. Their subsequent Cu-catalyzed cross-coupling with various alkyl (primary, secondary, tertiary, cyclic) Grignard reagents and Pd-catalyzed cross-coupling with aryl and alkenyl halides proceeded smoothly with essentially complete retention of stereochemical configuration to produce a wide variety of γ-, δ-, and e-chiral 1-alkanols of ≥99% ee. The MαNP ester analysis has been applied to the determination of the enantiomeric purities of δ-and e-chiral primary alkanols, which sheds light on the relatively undeveloped area of determination of enantiomeric purity and/or absolute configuration of remotely chiral primary alcohols.A symmetric synthesis remains as a significant challenge to synthetic organic chemists as the demand for enantiomerically pure compounds continues to increase. Chirality plays a vital role in chemical, biological, pharmaceutical, and material sciences. The US Food and Drug Administration requires that all chiral bioactive molecules have to be as pure as possible, containing a single pure enantiomer, because chirality significantly influences drugs' biological and pharmacological properties. As a consequence, development of new methods for asymmetric synthesis of enantiomerically pure compounds (≥99% ee) continues to be increasingly important (1-5). We recently reported a highly selective and efficient method (6) for the preparation of 2-chirally substituted 1-alkanols via a sequence consisting of (i) Zr-catalyzed asymmetric carboalumination of alkenes (ZACA reaction hereafter) (7-10)-in situ iodinolysis of allyl alcohol, (ii) enantiomeric purification by lipase-catalyzed acetylation (11, 12) of both (S)-and (R)-ICH 2 CH (R)CH 2 OH (1), the latter obtained as acetate, i.e., (R)-2, and (iii) Cu-or Pd-catalyzed cross-coupling (13, 14) (Scheme 1).As satisfactory as the procedure shown in Scheme 1 is, however, its synthetic scope is limited to the preparation of 2-chirally substituted 1-alkanols. In search for an alternative and more generally applicable procedure, we came up with a strategy shown in Scheme 2, which, in principle, should be applicable to the synthesis of γ-and more-remotely chiral alcohols of high enantiomeric purity. In contrast to Scheme 1, the alkylalane int...

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“…We studied on three chiral resolving agents [i.e., MαNP acid (2), MβNP acid (3), and M9PP acid (4)] based on their enantioresolution of chiral alcohols and elucidation of absolute configurations [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. The resolving ability of 2 is superior to that of 1 in normal phase HPLC.…”

Section: Introductionmentioning

confidence: 99%

Characteristic Conformation of Mosher’s Amide Elucidated Using the Cambridge Structural Database

2015

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Abstract:Conformations of the crystalline 3,3,3-trifluoro-2-methoxy-2-phenylpropanamide derivatives (MTPA amides) deposited in the Cambridge Structural Database (CSD) were examined statistically as Racid-enantiomers. The majority of dihedral angles (48/58, ca. 83%) of the amide carbonyl groups and the trifluoromethyl groups ranged from -30° to 0° with an average angle θ 1 of −13°. The other conformational properties were also clarified: (1) one of the fluorine atoms was antiperiplanar (ap) to the amide carbonyl group, forming a staggered conformation; (2) the MTPA amides prepared from primary amines showed a Z form in amide moieties; (3) in the case of the MTPA amide prepared from a primary amine possessing secondary alkyl groups (i.e., Mosher-type MTPA amide), the dihedral angles between the methine groups and the carbonyl groups were syn and indicative of a moderate conformational flexibility; (4) the phenyl plane was inclined from the O-Cchiral bond of the methoxy moiety with an average dihedral angle θ 2 of +21°; (5) the methyl group of the methoxy moiety was ap to the ipso-carbon atom of the phenyl group.

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Conformational Analysis of MαNP Esters, Powerful Chiral Resolution and ¹H NMR Anisotropy Tools – Aromatic Geometry and Solvent Effects on Δδ Values

Cited by 43 publications

References 55 publications

Chiral recognition of ethers by NMR spectroscopy

Chiral recognition of ethers by NMR spectroscopy

Highly enantioselective synthesis of γ-, δ-, and ε-chiral 1-alkanols via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA)–Cu- or Pd-catalyzed cross-coupling

Characteristic Conformation of Mosher’s Amide Elucidated Using the Cambridge Structural Database

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Conformational Analysis of MαNP Esters, Powerful Chiral Resolution and 1H NMR Anisotropy Tools – Aromatic Geometry and Solvent Effects on Δδ Values

Cited by 43 publications

References 55 publications

Chiral recognition of ethers by NMR spectroscopy

Chiral recognition of ethers by NMR spectroscopy

Highly enantioselective synthesis of γ-, δ-, and ε-chiral 1-alkanols via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA)–Cu- or Pd-catalyzed cross-coupling

Characteristic Conformation of Mosher’s Amide Elucidated Using the Cambridge Structural Database

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Conformational Analysis of MαNP Esters, Powerful Chiral Resolution and ¹H NMR Anisotropy Tools – Aromatic Geometry and Solvent Effects on Δδ Values