ACS Catalysis
Letter
(CD3)2 over (4-OMe-C6H4CH2)2O (10:1) within 1 h at room
temperature but without any significant deuterium exchange to
benzylic positions (Figure S1, SI).16 The absence of H/D
exchange to benzylic position is inconsistent with a mechanistic
path via a reversible alcohol-to-aldehyde dehydrogenation.
In an effort to detect catalytically relevant species, a 1:1
mixture of the complex 1 (0.1 mmol) and 4-methoxybenzyl
alcohol (0.14 mmol) in CD2Cl2 (0.6 mL) was monitored by
NMR. After 10 min at room temperature, the appearance of a
new species was observed along with the formation of free
benzene molecule (δ 7.26 ppm on 1H NMR), as indicated by a
new Ru−H signal at δ −10.95 ppm on 1H NMR and a
phosphine peak at δ 72.4 ppm by 31P{1H} NMR. We
tentatively assign the new set of peaks to an arene-coordinated
Ru−H complex [(4-OMe-C6H4CH2OH)(PCy3)(CO)-
would provide an operationally simple tool for synthesizing
functionalized ethers without using any reactive reagents or
protecting groups.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and methods, characterization data,
and NMR spectra of organic products. This material is available
AUTHOR INFORMATION
Corresponding Author
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Notes
RuH]+BF4 , in light of the previously observed arene exchange
−
The authors declare no competing financial interest.
reaction of 1.17
ACKNOWLEDGMENTS
Financial support from the National Science Foundation
(CHE-1358439) is gratefully acknowledged.
On the basis of these observations, we present a working
mechanistic hypothesis for the selective formation of unsym-
metrical ethers (Scheme 3). We propose that a cationic Ru-
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REFERENCES
Scheme 3. Working Mechanistic Hypothesis for
Unsymmetrical Ether Formation
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alkoxy species 5, initially generated from the deprotonation of
the alcohol substrate, is the key intermediate species for the
etherification reaction. Both carbon isotope effect and
Hammett data implicate the preferential C−O bond cleavage
from a more reactive alcohol substrate. A rapid epimerization of
an optically active indanol also supports the notion for the
selective C−O bond cleavage from a more reactive alcohol
substrate. To explain the retention of stereochemistry on the
less reactive alcoholic carbon, we suggest a SNi type of
nucleophilic displacement mechanism for the formation of α-
chiral ethers.13 As indicated by the Hammett study of phenol
substrates, the acidity of alcoholic substrate may be an
important factor in promoting the formation of Ru-alkoxy
species 5 from the deprotonation of a less reactive, more basic
alcohol substrate. The coordination of another alcohol
substrate and the liberation of water byproduct would facilitate
the regeneration of the alkoxy species 5. Still, many aspects on
how the catalyst can mediate a high degree of selectivity remain
unresolved, and detailed kinetic and computational studies are
warranted to elucidate the mechanism of unsymmetrical ether
formation.18
In summary, we successfully developed a highly selective
catalytic method for the direct etherification of two different
alcohols. A well-defined cationic ruthenium-hydride catalyst
exhibits uniquely high chemo- and stereoselectivity toward the
formation of unsymmetrically substituted and highly function-
alized α-chiral ethers. We anticipate that the catalytic method
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dx.doi.org/10.1021/cs5012537 | ACS Catal. 2014, 4, 3881−3885