Unexpected tosyl deprotection during osmium catalysed dihydroxylation

Article abstract of DOI:10.1016/j.tetlet.2007.11.058

Depending on the double bond position, tosyl deprotection was observed during olefin dihydroxylation using osmium tetroxide, leading to triols.

Full text of DOI:10.1016/j.tetlet.2007.11.058

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 566–568
Unexpected tosyl deprotection during osmium
catalysed dihydroxylation
*
´ ´
Frederic Batt, Olivier Piva and Fabienne Fache
` ˆ
Universite´ Lyon 1, CNRS, ICBMS, UMR 5246, Equipe Chimie Organique, Photochimie et Synthese Bat.Raulin,
43 Bd du 11 novembre 1918, Villeurbanne F-69622, France
Received 18 October 2007; revised 5 November 2007; accepted 9 November 2007
Available online 17 November 2007
Abstract—Depending on the double bond position, tosyl deprotection was observed during olefin dihydroxylation using osmium
tetroxide, leading to triols.
Ó 2007 Elsevier Ltd. All rights reserved.
The p-toluenesulfonate group (tosyl group) is widely
used as a leaving group in elimination or substitution
OH
R
OX
OsO , NMO
R
OTs
4
reactions. Conditions to recover the alcohol are most
of the time drastic and thus limit its use as a protecting
group. Among the different methods already published
to perform such a deprotection,1 the use of sodium
amalgam,2 low valent titanium,3 Na-naphthalenide4 or
magnesium in methanol5 have been reported. Micro-
wave assisted conditions6 or irradiation under UV light7
via an electron-transfer reaction were also applied with
success. Nevertheless, all these conditions are reductive
ones. In the course of our study on natural product
synthesis, we planned to replace a tosyl group by nucle-
ophilic substitution after having performed dihydroxyl-
ation of a double bond close to this group, using
osmium tetroxide. The diol thus obtained should be
selectively protected. To our surprise, only a triol was
isolated, resulting of the concomitant olefin dihydroxy-
lation and deprotection of the tosyl group (Fig. 1).
n
n
H O,
2
OH
O
n = 1or 2; X = H
n>2; X = OTs
Figure 1.
toluenesulfonate groups (entries 8–10) no deprotection
occurred and in the case of competition between an
alkylsulfonate and an arylsulfonate group only the ali-
phatic alcohol was regenerated (entries 4, 9 and 10). Sul-
fonamide remained untouched (entry 12) while the
mesyl group was also deprotected (entry 11) probably
due to the well-known difference of strength between
the N–SO2 and the O–SO2 bonds. In the case of com-
pound depicted in entry 3, Sharpless AD-mix system
was also tested leading to the triol. In view of under-
standing the mechanism, we performed several experi-
ments: first, NMO alone was tried on product 1, but
no reaction occurred, the starting material was totally
recovered. We also performed the reaction with N-methyl-
morpholine, the reduction product of NMO during
the osmium oxidation catalytic cycle, without success.
Intermolecular experiments, using 1-hexene and product
7 also failed. At this stage of our study, we assume that
the formation of the generally admitted intermediate in
OsO4 catalytic dihydroxylation, the osmate ester C,
close to the tosyl group is necessary to allow its depro-
tection (Fig. 2). This cyclic species C should be attacked
by water, leading to the open hemi osmate ester D which
thereafter should undergo a nucleophilic substitution by
Results are collected in Table 1.
This process has been applied to various substrates and
under the aforementioned conditions either a triol, when
2 or 3 carbons are present between the tosyl group and
the double bond (entries 1–4) or a diol, when the dis-
tance is higher (entries 5 and 6) or in the absence of a
double bond (entry 7) was obtained. In the case of aryl-
Keywords: Dihydroxylation; Tosyl group deprotection; Osmium
tetroxide; Triol synthesis.
*
Corresponding author. Tel.: +33 047 244 8521; fax: +33 047 244
8136; e-mail: fache@univ-lyon1.fr
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.11.058

F. Batt et al. / Tetrahedron Letters 49 (2008) 566–568
567
Table 1. Results of oxidation with OsO4
Entry
Substrate
Product
Conversion, %
(isolated yield, %)
HO
OH
OH
OTs
1
100 (83)
100
1
OH
OTs
OH
2
3
HO
HO
2
HO
HO
O
TsO
92a (90) 60b
O
O
O
3
OTs
OH
4
5
100 (70)
100
HO
HO
OH
4
OTs
OTs
5
OH
OH
OTs
OTs
OH
OTs
6
7
100
0
6
7
—
OTs
OTs
OTs
OH
8
9
100
100
8
OH
OTs
OH
OH
OH
9
OTs
OTs
OH
OTs
A
OH
10
100 (A: 43) (B: 27)
OTs
OH
10
OTs
OH
B
OH
HO
OH
OMes
11
12
100 (80)
100c
11
Ts
N
OH
Ts
N
HO
H
H
12
Conditions: see typical procedure.
a After 4 h, using 10% OsO4, NMO.
b After 60 h using AD-mixb, 0.2% OsO4.
c 1% of OsO4 was added after 4 h of reaction.

568
F. Batt et al. / Tetrahedron Letters 49 (2008) 566–568
(OsO4/NMO system), so long as the C@C bond is close
enough to the sulfonate function, leading to a triol.
O
Ar
O
O
S
O
Os
O
O
O
In a typical procedure, 0.16 mmol of a substrate bear-
ing both a tosyl group and a double bond was dissolved
in a volume/volume mixture of acetone/water (0.8 mL
of each). N-Methyl morpholine-N-oxide (NMO,
0.16 mmol) and 1% of OsO4 in water (4 wt %) were
added and the reaction mixture allowed to stir at room
temperature for 20 h. After extraction with AcOEt and
drying with MgSO4, the crude mixture was analysed
O
S
OsO
4
R
O
Ar
n
R
NMO
O
C
n = 1 or 2
H O
2
1
by H NMR, to control the presence or not of the tosyl
H
O
Ar
O
group. Column chromatography on silica (AcOEt/
petroleum ether: 50/50) could be performed to isolate
the reaction product with good yield.
O
S
O
O
Os
H
O
O
O
R
OH
n
2
References and notes
n = 1 or 2
D
1. Greene, T. W.; Wuts, P. G. M. Protecting Groups in
Organic Synthesis, 3rd ed.; Wiley: New York, 1999.
2. Ranganathan, R.; Larwood, D. Tetrahedron Lett. 1978, 19,
4341.
Figure 2.
a second molecule of water, thus liberating the tosyl
group. Assistance of the osmium part of D via hydrogen
bond should also be considered to explain the necessity
of proximity between the tosyl group and the double
bond to ensure the deprotection. This proposed mecha-
nism is consequent with experimental results obtained
with arylsulfonates which were totally recovered, nucle-
ophilic substitution being impossible on aryl sp2 carbons
(entries 8–10).
3. Nayak, S. K. Synthesis 2000, 575.
4. Suzuki, H.; Unemoto, M.; Hagiwara, M.; Ohyama, T.;
Yokoyama, Y.; Murakami, Y. J. Chem. Soc., Perkin Trans.
1 1999, 1717.
5. Sridhar, M.; Kumar, B. A.; Narender, R. Tetrahedron Lett.
1998, 39, 2847.
6. Sabitha, G.; Abraham, S.; Subba Reddy, B. V.; Yadav, J. S.
Synlett 1999, 1745.
7. Pete, J. P.; Portella, C. Bull. Soc. Chim. Fr. 1980, 5–6, 275;
Nishida, A.; Hamada, T.; Yonemitsu, O. J. Org. Chem.
1988, 53, 3387.
In conclusion, we have shown here that the tosyl group
can be cleaved during a dihydroxylation procedure