Organic Letters
Letter
(6) Du, Z.-X.; Zhang, L.-Y.; Fan, X.-Y.; Wu, F.-C.; Da, C.-S.
Tetrahedron Lett. 2013, 54, 2828.
tion process was developed using a cation-binding Song’s
oligoEG catalyst with KF as base. A wide range of racemic aldols
were resolved with unprecendentedly high selectivity factors (s =
up to 2393) under mild reaction conditions. This protocol is
easily scalable and provides an alternative approach for syntheses
of diverse biologically and pharmaceutically relevant chiral aldols
such as gingerols in enantiomerically pure form. The great
success of these kinetic resolutions can be ascribed to systematic
cooperative hydrogen-bonding catalysis in a densely confined
chiral space, which mimics the action of enzymes. Current efforts
in our laboratory are focused on detailed mechanistic studies to
elucidate the origin of the stereo-outcome. Biological evaluations
of chiral gingerols are also in progress. Results will be reported in
due course.
(7) (a) For a review, see: Oliveira, M. T.; Lee, J.-W. ChemCatChem
2017, 9, 377. (b) Yan, H.; Jang, H. B.; Lee, J.-W.; Kim, H. K.; Lee, S. W.;
Yang, J. W.; Song, C. E. Angew. Chem., Int. Ed. 2010, 49, 8915. (c) Yan,
H.; Oh, J. S.; Lee, J.-W.; Song, C. E. Nat. Commun. 2012, 3, 1212.
(d) Park, S. Y.; Lee, J. W.; Song, C. E. Nat. Commun. 2015, 6, 7512.
(e) Li, L.; Liu, Y.; Peng, Y.; Yu, L.; Wu, X.; Yan, H. Angew. Chem., Int. Ed.
2016, 55, 331. (f) Liu, Y.; Ao, J.; Paladhi, S.; Song, C. E.; Yan, H. J. Am.
Chem. Soc. 2016, 138, 16486. (g) Vaithiyanathan, V.; Kim, M. J.; Liu, Y.;
Yan, H.; Song, C. E. Chem. - Eur. J. 2017, 23, 1268. (h) Kim, M. J.; Xue,
L.; Liu, Y.; Paladhi, S.; Park, S. J.; Yan, H.; Song, C. E. Adv. Synth. Catal.
2017, 359, 811. (i) Yu, L.; Wu, X.; Kim, M. J.; Vaithiyanathan, V.; Liu, Y.;
Tan, Y.; Qin, W.; Song, C. E.; Yan, H. Adv. Synth. Catal. 2017, 359, 1879.
(j) Park, S. Y.; Hwang, I.-S.; Lee, H. J.; Song, C. E. Nat. Commun. 2017,
8, 14877. (k) Tan, Y.; Luo, S.; Li, D.; Zhang, N.; Jia, S.; Liu, Y.; Qin, W.;
Song, C. E.; Yan, H. J. Am. Chem. Soc. 2017, 139, 6431. (l) Duan, M.; Liu,
Y.; Ao, J.; Xue, L.; Luo, S.; Tan, Y.; Qin, W.; Song, C. E.; Yan, H. Org.
Lett. 2017, 19, 2298. (m) Paladhi, S.; Liu, Y.; Kumar, B. S.; Jung, M.-J.;
Park, S. Y.; Yan, H.; Song, C. E. Org. Lett. 2017, 19, 3279. (n) Park, S. Y.;
Liu, D.; Oh, J. S.; Kweon, Y. K.; Jeong, Y. B.; Duan, M.; Tan, Y.; Lee, J.-
W.; Yan, H.; Song, C. E. Chem. - Eur. J. 2018, 24, 1020.
(8) Remarkably, α-substitution changes the resolution pathway. Thus,
α-substituted β-hydroxy ketones were resolved exclusively via retro-
aldol pathway with reasonable selectivity factors. A comprehensive study
on retro-aldolase mimic kinetic resolution of racemic aldols is currently
in progress, and the results will be reported elsewhere in due course.
(9) We examined two more catalysts (X = H or Ph) having no electron-
withdrawing substituents at the 3,3′-position. However, these catalysts
were completely inactive in the same reaction conditions, further
confirming the importance of suitable acidity for phenolic protons. The
importance of the polyether chain was also confirmed unambiguously by
replacing the polyether of 1a with the alkyl chain. This catalyst also
showed no activity, indicating that the polyether backbone is crucial in
achieving the observed catalytic activity.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
Experimental details and analytical data (PDF)
AUTHOR INFORMATION
■
Corresponding Author
ORCID
Author Contributions
∥S.P. and I.-S.H. contributed equally.
Notes
(10) Fiaud, J. C.; Kagan, H. B. Kinetic Resolution. In Topics in
Stereochemistry; Eliel, E. L., Wilen, S. H., Ed.; Wiley and Sons, Inc.: New
York, 1988; Vol. 18, p 249.
(11) Fukuyama, T.; Tokuyama, H. Aldrichimica Acta 2004, 37, 87.
(12) Bae, H. Y.; Sim, J. H.; Lee, J.-W.; List, B.; Song, C. E. Angew. Chem.,
Int. Ed. 2013, 52, 12143.
(13) Cross-aldol reactions of aldehydes: (a) Alcaide, B.; Almendros, P.
Angew. Chem., Int. Ed. 2003, 42, 858. (b) Denmark, S. E.; Bui, T. Proc.
Natl. Acad. Sci. U. S. A. 2004, 101, 5439.
(14) For a review, see: Semwal, R. B.; Semwal, D. K.; Combrinck, S.;
Viljoen, A. M. Phytochemistry 2015, 117, 554.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the Korean Research Foundation
(Grant No: NRF-2017R1A2A1A05001214 and NRF-
2016R1A4A1011451).
REFERENCES
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