Chiral imine copper chloride-catalyzed enantioselective desymmetrization of 2-substituted 1,2,3-propanetriols
- Center for Molecular Design and Synthesis, Department of Chemistry, School of Molecular Science (BK21), Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea
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Edited by Jack Halpern, University of Chicago, Chicago, IL, and approved November 28, 2006 (received for review September 7, 2006)
Abstract
Catalytic enantioselective desymmetrization of meso-2-substituted glycerols has been developed to secure a novel synthetic route to chiral tertiary alcohols. The transformation has been realized by monobenzoylation using benzoyl chloride and triethylamine in the presence of the imine ligand (25)-CuCl2 complex in THF at ambient temperature. The desymmetrization turned out to be greatly dependent on acylating reagent, base, solvent, and needless to say, catalyst. Extensive screening of chiral ligands led us to combine bromopyridinecarboxaldehyde 1 and phenyloxazoline amine 12 derived from tert-leucine, the bromo and phenyl substituents of which proved to be indispensable. All of the substrates have been desymmetrized to the corresponding monobenzoates with high enantioselectivity up to 96% enantiomeric excess. The catalytic system allows broad structural diversity of substrates and its synthetic versatility has been demonstrated by an efficient synthetic route to a known key precursor 68 of triazole antifungals.
Footnotes
- *To whom correspondence should be addressed. E-mail: shkang{at}kaist.ac.kr
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Author contributions: S.H.K. designed research; B.J. performed research; B.J. and S.H.K. contributed new reagents/analytic tools; B.J. and S.H.K. analyzed data; and S.H.K. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS direct submission.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0607865104/DC1.
- Abbreviation:
- ee,
- enantiomeric excess.
- © 2007 by The National Academy of Sciences of the USA
