Assignment of the Absolute Configuration of Polyfunctional Compounds by NMR Using Chiral Derivatizing Agents

Seco, José Manuel; Quiñoá, Emilio; Riguera, Ricardo

doi:10.1021/cr2003344

Cited by 185 publications

(164 citation statements)

References 147 publications

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“…The geometry of the two double bonds was determined as E by the large coupling constants of H-2/H-3 ( by the modified Mosher's methods. 16 Following the methylation of compound 1 by dimethyl sulfate, the (R)-and (S)-MTPA esters of the methylated derivative (1a) were synthesized. [17][18][19] The positive Dd values (d S -d R ) of H-2 (+0.22 ppm) and H-3 (+0.07 ppm) and the negative ones of H-5 (À0.08 ppm) and H-6 (À0.22 ppm) indicated the S configuration of C-4.…”

Section: Introductionmentioning

confidence: 99%

Lipid-lowering polyketides from a soft coral-derived fungus Cladosporium sp. TZP29

Zhu

Gao

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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Section: Introductionmentioning

confidence: 99%

Lipid-lowering polyketides from a soft coral-derived fungus Cladosporium sp. TZP29

Zhu

Gao

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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“…The absolute configuration of 4 at C-8' was determined by the modified Mosher's method [16]. Based on the Δδ values of the (S)-and (R)-MTPA esters (4a and 4b) (Fig.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Adeninealkylresorcinol, the first alkylresorcinol tethered with nucleobase from Lasiodiplodia sp.

Gao

Sun

et al. 2016

Fitoterapia

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“…Many CDAs including α-methoxy-α-(trifluoromethyl) phenylacetic acid (MTPA or Mosher acid) (24) have been developed for determining the absolute configurations and/or enantiomeric excess of secondary alcohols (24)(25)(26)(27). However, few papers reported examples of primary alcohols, which mainly focused on the cases of β-chiral primary alcohols (28)(29)(30)(31)(32).…”

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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Assignment of the Absolute Configuration of Polyfunctional Compounds by NMR Using Chiral Derivatizing Agents

Cited by 185 publications

References 147 publications

Lipid-lowering polyketides from a soft coral-derived fungus Cladosporium sp. TZP29

Lipid-lowering polyketides from a soft coral-derived fungus Cladosporium sp. TZP29

Adeninealkylresorcinol, the first alkylresorcinol tethered with nucleobase from Lasiodiplodia sp.

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

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