Organic Letters
Letter
1
mechanistic studies were performed, with de-O-acetylation of
peracetylated methyl-α-glucoside 1 being used as a probe to
monitor the reactivity of reducing agents obtained from various
mixtures of zirconium salts and metal hydrides (Table 2).
Experimental procedures, characterization data, and H
and 13C NMR spectra for compounds 2−25 (PDF)
AUTHOR INFORMATION
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Corresponding Author
ORCID
Table 2. Influence of the Zirconium Source and Reducing
Agent
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
zirconium
(equiv)
conv
a
selectivity (2:
■
a
entry
hydride (equiv)
(%)
others)
LABEX SynOrg (ANR-11-LABX-0029) and ANR (JCJC-
2013-QuatGlcNAc) are gratefully acknowledged for their
financial support. T.C. (Normandy University) and T.L.
(CNRS) are also supported by individual research fellowships.
1
2
3
Cp2ZrCl2 (3.5)
Cp2ZrCl2 (3.5)
Cp2ZrCl2 (3.5)
DIBAL-H (3)
LiEt3BH (3)
96
60
88
97:3
74:26
63:37
Al(OtBu)3H
(3)
4
5
Cp2ZrHCl
(3.5)
Cp2ZrHCl
(3.5)
20
84
n/a
REFERENCES
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DIBAL-H (3)
90:10
́
a
1
Chem. 2018, 2, 35−46. (b) Shugrue, C. R.; Miller, S. J. Chem. Rev.
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Measured by H NMR analysis of the crude.
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We indeed made the assumption that the primary alcohol 2
should be nicely obtained when the proper reactive species
would be present in the reaction media, otherwise low
conversion and/or selectivity would be observed. Whereas in
situ reduction of Cp2ZrCl2 by DIBAL-H14b gave 2 in high yield
with a complete selectivity (entry 1), the use of LiEt3BH (entry
2)14a and Al(OtBu)3H (entry 3)14c delivered complex
mixtures. Moreover, freshly prepared Schwartz’ reagent21
resulted in a very low conversion from which selectivity
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Cp2ZrHCl finally resulted in almost complete conversion and
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In conclusion, a combination of DIBAL-H and Cp2ZrCl2 in
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commonly used in carbohydrate chemistry, and numerous
functionalities found in bioactive compounds and natural
products. This broad scope and highly tolerant site-selective
deprotection of peracetylated substrates should provide new
opportunities to solve selectivity issues in multistep organic
synthesis. Deeper mechanistic studies are currently underway
in our laboratory to identify the active reducing species leading
to this transformation.
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ASSOCIATED CONTENT
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* Supporting Information
The Supporting Information is available free of charge on the
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Org. Lett. XXXX, XXX, XXX−XXX