lytic system was observed.6 Cyclic ruthenates are envisioned
to be key intermediates in both monooxidation and ketohy-
droxylation (Scheme 2). If Oxone reacts as a nucleophilic
proceeds with either oxidation system. However, the use of
reoxidants other than Oxone in the oxidation of the corre-
sponding glycol 1 resulted in a predominant formation of
fission product 4.
Diols are known to react with ruthenium(VIII)-oxide I in
a reversible condensation reaction to give cyclic ruthenates
III or IV,8 which are proposed intermediates in the related
ketohydroxylation.6 Our working model is based upon the
assumption that the strongly electron-withdrawing ruthenium
in III or IV sets an electronic bias, thus orchestrating the
Scheme 2. Regioselective monooxidation-A Proposal
2-
irreversible addition of SO5 with a preferred trajectory
leading to the cleavage of the less electron-rich of the two
Ru-O bonds in III or IV (Scheme 2). The resulting peroxo
ester V reacts via a â-hydride elimination to furnish ketol
VI and regenerates RuO4 I. The observed product distribution
indicates the existence of cyclic ruthenates such as III or
IV. Fission products such as 4 can be obtained via a
competing electrocyclic fragmentation of III or IV.9 Re-
cently, we found a significant rate acceleration in the related
ruthenium-catalyzed dihydroxylation by addition of protic
acids.9 Ruthenate III can be activated for a nucleophilic
addition via a protonation pathway in analogy to the acid-
catalyzed saponification of carboxylates. The combination
reoxidant in either process, the oxidation of unsymmetrical
Vic-diols should furnish acyloins with high regioselectivity.
Hence, diol 1 was oxidized with RuO4 in the presence of
different reoxidants (Table 1).
2-
of protonation of III and nucleophilic character of SO5
accelerates the nucleophilic addition of the reoxidant to the
metal center in IV resulting in the observed high regiose-
lectivity for the monooxidaton process.
With these results in hand, we investigated the oxidation
of enantioenriched Vic-diols derived from simple alkenes via
an asymmetric Sharpless dihydroxylation. Apart from the
regioselectivity, the scope and limitation as well as the
question whether the acidic reaction media could lead to an
epimerization are important issues that have to be addressed.
The results are outlined in Table 2. Different alkenes were
transformed into the corresponding enantioenriched acyloins
with remarkably high regioselectivity. The enantiomeric
excess of both diol and ketol was determined by chiral
HPLC. Importantly, an acid-assisted epimerization of R-ke-
tols was not obserVed in any case within the time frame of
the monooxidation. The assignment of absolute configuration
is based upon comparison with the literature or the mnemonic
device.4 A broad scope of functional groups is tolerated.
Acetates or chlorides can be oxidized in high yields and
excellent regioselectivities.
Table 1. Influence of Reoxidant on Product Distribution
entry
reoxidant
NaOCl
NaIO4
K2S2O8
KBrO3
Oxone/NaHCO3
2:3:4a
conversion [%]a
1
2
3
4
5
41:4:55
12:0:88
n.d.
15:0:85
92:0:8
75
98
21
47
96
a Determined by GC integration.
Apart from Oxone, neither of the common reoxidants
could be used for a selective monooxidation of diol 1. Using
a combination of Oxone/NaHCO3 R-hydroxy ketone 2 was
formed exclusively. This result corresponds to the product
distribution obtained in the direct ketohydroxylation of
1-octene.6 From a mechanistic point of view a simple
oxidation of the secondary alcohol in 3 by RuO4 was ruled
out on the basis of the results in separate control experiments
on the oxidation of 2-octanol to 2-octanone. The reaction
Interestingly, electron-rich diols are oxidized more slowly
than electron-poor substrates. Whereas the reaction of diol
6 (entry 3, Table 2) proceeded within 1 h, the oxidation of
sulfone 10 (entry 7, Table 2) was complete after 30 min.
Since the initial condensation between RuO4 I and diol II
appears to be a reversible process (which is a basic require-
ment in the dihydroxylation), the hydrolysis of more electron-
rich ruthenates III eventually outcompetes the irreversible
nucleophilic attack of oxone (Scheme 2).9 This hypothesis
is further underlined by the fact that a reduction of the total
(7) (a) D’Accolti, L.; Detomaso, A.; Fusco, C.; Rosa, A.; Curci, R. J.
Org. Chem. 1993, 58, 3600. (b) Curci, R.; D’Accolti, L.; Dinoi, A.; Fusco,
C.; Rosa, A. Tetrahedron Lett. 1996, 37, 115. Desymmetrisation of meso-
diols: (c) Adam, W.; Saha-Mo¨ller, C. R.; Zhao, C.-G. J. Org. Chem. 1999,
64, 7492 and references therein.
(8) Carlsen, P. H. J.; Katsuki, T.; Martin, V. S.; Sharpless, K. B. J. Org.
Chem. 1981, 46, 3936.
(9) Plietker, B.; Niggemann, M. Org. Lett. 2003, 5, 3353.
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Org. Lett., Vol. 6, No. 2, 2004