SmI2/water/amine mediates cleavage of allyl ether protected alcohols: application in carbohydrate synthesis and mechanistic considerations.

Article abstract of DOI:10.1021/ol0354831

[reaction: see text]. SmI2/H2O/amine provides selective cleavage of unsubstituted allyl ethers in good to excellent yields. This method is therefore useful in deprotection of alcohols and carbohydrates.

Full text of DOI:10.1021/ol0354831

ORGANIC
LETTERS
2003
Vol. 5, No. 22
4085-4088
SmI2/Water/Amine Mediates Cleavage of
Allyl Ether Protected Alcohols:
Application in Carbohydrate Synthesis
and Mechanistic Considerations
Anders Dahle´n,† Andreas Sundgren,† Martina Lahmann,† Stefan Oscarson,‡ and
,†
Go1ran Hilmersson*
Department of Chemistry, Go¨teborg UniVersity, SE-412 96 Go¨teborg, Sweden,
and Department of Organic Chemistry, Stockholm UniVersity,
SE-106 91 Stockholm, Sweden
hilmers@organic.gu.se
Received August 6, 2003
ABSTRACT
SmI2/H O/amine provides selective cleavage of unsubstituted allyl ethers in good to excellent yields. This method is therefore useful in deprotection
2
of alcohols and carbohydrates.
7
The protection and deprotection of alcohols is a central topic
in organic synthesis, in particular in carbohydrate synthesis.
A valuable protecting group is the allyl group, due to the
high stability of allyl ethers under a wide range of reaction
conditions.1 It is therefore not surprising that a large number
of deallylation methods have been developed. The conven-
tional methods of deprotection combine a transition-metal-
catalyzed isomerization (Pd, Rh, or Ir) of the double bond
to the enol ether and subsequent hydrolysis of the latter to
furnish the corresponding alcohol.2
NaI/Me3SiCl,6 Pd(PPh3)4 with NaBH4 or Bu3SnH8 as re-
ducing agent, and NiCl2(dppp)/DIBALH9 have been reported.
The single electron-transfer agent SmI2 has received much
interest for its reducing properties both in selective reductions
and reductive couplings.10
Previously, we have shown that the combination of amine
and water in the SmI2/water/amine reagent mixture mediates
fast reductions of ketones, R,â-unsaturated esters, alkyl and
aryl halides, and conjugated alkenes.11 We now report on
the use of the SmI2/water/amine reagent system, rendering
Recently, some one-step procedures for the cleavage
of allyl ethers, e.g., PdCl2/CuCl/O2,3 PdCl2,4 SmCl3,5
(3) Mereyala, H. B.; Guntha, S. Tetrahedron Lett. 1993, 34, 6929-6930.
(4) Ogawa, T.; Nakabayashi, S.; Kitajima, T. Carbohydr. Res. 1983, 114,
225-236.
† Go¨teborg University.
‡ Stockholm University.
(5) Espanet, B.; Dun˜ach, E.; Pe´richon, J. Tetrahedron Lett. 1992, 33,
2485-2488.
(1) (a) Gigg, R.; Conant, R. Carbohydr. Res. 1982, 100, C5-C9. (b)
Guibe, F. Tetrahedron 1997, 40, 13509-13556.
(6) Kamal, A.; Laxman, E.; Rao, N. V. Tetrahedron Lett. 1999, 40, 371-
(2) (a) Gent P. A.; Gigg, R. J. Chem. Soc., Chem. Commun. 1974, 277-
278. (b) Gigg, R. Conant, R. J. Chem. Soc., Perkin Trans. 1 1973, 17,
1858-1863. (c) Bieg, T.; Szeja, W. J. Carbohydr. Chem. 1985, 140, C7-
C8. (d) Chandreskhar, S.; Reddy, C. R.; Rao, R. J. Tetrahedron 2001, 44,
3435-3438. Boullanger, P.; Chatelard, P.; Descotes, G.; Kloosterman, M.;
Van Boom, J. H. J. Carbohydr. Chem. 1986, 5, 541-559. (e) Oltvoort, J.
J.; van Boeckel, C. A. A.; de Koning, J. H.; van Boom, J. H. Synthesis
1981, 305-308.
374.
(7) Beugelmans, R.; Bourdet, S.; Bigot, A.; Zhu, J. Tetrahedron Lett.
1994, 35, 4349-4350.
(8) Zang, H. X.; Guibe´, F.; Balavoine, G. Tetrahedron Lett. 1988, 29,
619-622.
(9) (a) Taniguchi, T.; Ogasawara, K. Angew. Chem., Int. Ed. 1998, 37,
1136-1137. (b) Taniguchi, T.; Ogasawara, K. J. Chem. Soc., Chem.
Commun. 1998, 1531-1532.
10.1021/ol0354831 CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/01/2003

a simple method for the selective cleavage of allyl ethers.
The cleavage reaction is clean and proceeds in almost
quantitative yield at room temperature.
During our course of exploring the SmI2/water/amine-
mediated intramolecular coupling reactions with aryl bro-
mides, we observed that unsubstituted allyl ethers as sub-
strates were cleaved rather than converted into their expected
coupling products.12
substrates were rapidly and cleanly deprotected. To inves-
tigate the scope of the SmI2/water/amine system for the de-
allylation of carbohydrates, some different protected deriva-
tives bearing one or more allyl groups were employed (entries
7-12).
The cleavage of allyl groups from carbohydrate derivatives
turned out to be more delicate than for the less functionalized
alcohols. A major drawback is the reduction of ester groups,
but benzyl, benzylidene, and silyl ether groups (not shown)
withstand the reaction conditions (entries 7-11). Further-
more, the thioethyl group, valuable for consecutive glyco-
sylation, does not interfere with the SmI2 mixture (entries 9
and 10). An unexpected result is the resistance of the
anomeric allyl group. Different allyl glycosides tested (e.g.,
entry 11) remained unchanged after elongated reaction times
(>1 d). It is even possible to remove primary and secondary
allyl ethers without destroying the anomeric allyl group (entry
12). An advantage of this new method is the simple removal
of multiple allyl groups in one step (entry 12), which can be
difficult to accomplish by standard methods.
After 5 min at ambient temperature, allyloxybenzene was
converted to the corresponding phenol using a mixture of
SmI2, water, and triethylamine (Scheme 1).13 Extended
Scheme 1. Cleavage of Allyloxybenzene Using SmI2/H2O/
Aminea
a Key: (i) SmI2/H2O/Et3N, rt, 5 min, >90%.
Since it is known that the relative rate of isomerization
versus the rate of cleavage depends on the promoting system,
the effect of alkyl substitution at different carbons of the
allyl group was also investigated (Table 2).16 Slow cleavage
(5 h) was observed with an R-methylated allyl group (entry
1), while no deprotection occurred with substrates bearing a
branching (entry 2) or elongating (entry 3) methyl substituent
directly on the double bond. Thus, the alkyl substituent
stabilizes the allyl group to an extent that reductive cleavage
cannot proceed. The corresponding allylamine (entry 4) or
sulfide (entry 5) proved to be completely inert to the reaction
conditions.
reaction times with excess SmI2 also produced a second
product, 3-cyclohexene-1-ol.14
The aliphatic analogue, allyloxycyclohexane, was also
converted to the corresponding alcohol although the reaction
was considerably slower (Scheme 2). Using a primary amine
Scheme 2. Cleavage of Allyloxycyclohexane Using SmI2/
H2O/Aminea
Initially, we anticipated that the SmI2/water/amine mixture
promoted the isomerization of the allyl ether to the corre-
sponding enol ether, followed by hydrolysis of the latter
either directly or during acidic workup. However, a vinyl
ether, i.e., an isomerized allyl ether, stayed unchanged after
treatment with SmI2/water/amine (entry 6). Obviously, the
SmI2/water/amine system mediates direct cleavage of the
allyl ether. Furthermore, the carbon connected to the oxygen
bridge, originating from the alcohol, is left unchanged.
Consequently, a chiral allyl ether, prepared from an enan-
tiomeric pure alcohol, gave no racemisation at the stereogenic
carbon (entry 7).
Details about the byproducts formed in the reaction were
necessary in order to clarify the reaction pathway. Un-
fortunately, we were unable to detect any traces or remains
of the allyl group in the reactions summarized in Tables 1
and 2.
a Key: (i) SmI2/H2O,Et3N, rt, 2 h, >99%; (ii) SmI2/H2O/i-
OPrNH2, rt, 1 min, >99%.
as base, e.g., isopropylamine, instead of triethylamine
accelerated the deprotection step remarkably (approximately
75-100 times).15
Several different primary and secondary aliphatic allylic
alcohols were synthesized and subjected to the SmI2/water/
isopropylamine reaction conditions in order to explore the
versatility of this method (Table 1, entries 1-6). All these
(10) (a) Molander, G. A. Organic Reactions; Paquette, L. A., Ed.; John
Wiley & Sons: New York, 1994; Vol. 46, pp 211-367. (b) Molander, G.
A. Radicals in Organic Synthesis; Renand, P., Sibi, M. P., Ed.; Wiley-
VCH: Weinheim, 2001; Vol. 1, pp 153-182. (c) Taniguchi, N.; Uemura,
M. J. Am. Chem. Soc. 2000,122, 8301-8302. (d) Lodberg, H.; Christensen,
T. B.; Enemaerke, R. J.; Daasbjerg, K.; Skrydstrup, T. Eur. J. Org. Chem.
1999, 565-572. (e) Rivkin, A.; Nagashima T.; Curran, D. P. Org. Lett.
2003, 5, 419-422. (f) Keck, G. E.; Truong, A. P. Org Lett. 2002, 4, 3131-
3134. (g) Annunziata, R.; Benaglia, M.; Caproale, M.; Raimondi, L.
Tetrahedron: Asymmetry 2002, 13, 2727-2734. (h) Dinesh, C. U.; Reissig,
H.-U. Angew. Chem., Int. Ed. 1999, 38, 789-791.
(11) (a) Dahle´n, A.; Hilmersson, G. Tetrahedron Lett. 2002, 43, 7197-
7200. (b) Dahle´n, A.; Hilmersson, G. Chem. Eur. J. 2003, 9, 1123-1127.
(c) Dahle´n, A.; Hilmersson, G.; Knettle, B. W.; Flowers, R. A., II. J. Org.
Chem. 2003, 68, 4870-4875. (d) Dahle´n, A.; Hilmersson, G. Tetrahedron
Lett. 2003, 44, 2661-2664.
(12) Dahle´n, A.; Peterson, A.; Hilmersson, G. Org. Biomol. Chem. 2003,
1, 2423-2426.
Assuming that an allyl radical is the intermediate that is
formed first, there are several possibilities to continue. The
(13) SmI2 is commercially available but it is also easily prepared in good
yields and at low cost from powder of samarium and iodine in THF in an
ultrasonic bath (see the Supporting Information).
(14) Kamochi, Y.; Kudo, T. Tetrahedron Lett. 1994, 35, 4169-4172.
(15) Employing n-butylamine, another primary amine, we observed
similar rates as with isopropylamine for the deallylation reaction.
(16) Kocien´ski, P. J. In Protecting Groups: Thieme foundations of
organic chemistry series; Enders, D., Noyori, R., Trost, B. M., Eds.;
Thieme: Stuttgart, New York, 1994; p 62.
4086
Org. Lett., Vol. 5, No. 22, 2003

Table 1. Deallylation of Various Alcohols Using SmI2/H2O/i-PrNH2
a Isolated yields are based on a 100 mg scale of substrate (1 equiv) using SmI2 in THF (5 equiv/allyl group), i-PrNH2 (20 equiv), and H2O (15 equiv) as
reagents. b The product allyl mannoside was isolated as a tetraacetate in order to simplify the workup.
radical can either dimerize, polymerize, or be quenched
directly by receiving another electron and a proton to yield
Table 2. Exploring the Scope of the Cleavage Reaction Using
propene, which we cannot detect. Therefore, a substituted
allyl ether with a pentyl group on the allylic carbon was
prepared and subjected to SmI2/water/i-PrNH2 to elucidate
the remainder of the allyl group after the cleavage reaction
(Scheme 3). After workup, only n-decanol and octene, but
no traces of any reduced or dimerized octane, were observed.
Interestingly, besides 1-octene, a mixture of cis- and trans-
2-octene was detected by GC-MS, which shows a 1,3-
isomerization to some extent.11d
SmI2/H2O/i-PrNH2
Based on this result, we suggest the following mechanism
for the SmI2/water/amine-mediated cleavage of allyl ethers
(Scheme 3). Samarium(II) is oxidized to Sm(III), while the
electron is received by the carbon-oxygen bond, which is
then cleaved. The alkoxide anion becomes an additional
ligand to Sm(III). This strong Lewis acid readily attracts two
hydroxides from the water. The two released iodides (I-)
and the two remaining protons precipitate as a quarternary
iodine salt (R3N×HI). An additional water molecule is
needed to regenerate the unprotected alcohol and insoluble
Sm(OH)3. The unpaired electron of the resonance stabilized
allyl radical reacts immediately with another set of SmI2/
water/amine to give the alkene, Sm(OH)3 and R3N×HI. The
order and details of the electron and the proton transfers may
be more complicated.
Org. Lett., Vol. 5, No. 22, 2003
4087

Scheme 3. Suggested Mechanism for the SmI2/Water/
Table 3. Subsequent Deoxygenation of Alcohols Containing a
Good Radical Stabilizing Group
Amine-Mediated Cleavage of Allyl Ethers
In addition, for substrates containing a good radical
stabilizing group, e.g., benzylic, to the allyloxy group, an
unexpected deoxygenation reaction was observed (Table 3).
First the allyl group is cleaved, followed by the deoxygen-
ation reaction.
In summary, it has been demonstrated that the SmI2/water/
amine reagent system is an attractive alternative to other
deallylation methods, exhibiting unique reactivity. The
deallylation reactions occurred with high yields and chemose-
lectivity. However, the presence of ketones, esters (in par-
ticular R,â-unsaturated esters) or conjugated dienes precludes
selective deallylation as reduction of these functional groups
is instantaneous under these conditions.
Kinetic experiments showed that the reaction between the
allyl ether allyloxy cyclohexane and SmI2/water/amine
proceeds with first-order kinetics in both SmI2 and amine
and zero order in water. Although the reaction order in water
is zero, the reaction still requires 2.5-3 equiv of water/SmI2
for completion. No more than 3 equiv of water per SmI2
should be used since excess water appeared to retard the
reaction, most likely due to unwanted breakdown of SmI2.
The reaction order of zero in water is not surprising since
the water molecules are already coordinated to samarium
in the initial state according to UV/vis studies.11c Further-
more, we observed no kinetic isotope effect, i.e., kH2O/kD2O
) 1.0.
Acknowledgment. We (G.H. and S.O.) thank the Swed-
ish Research Council (Vetenskapsrådet) for financial support.
Annika Petersson is also acknowledged for preliminary
results with allyloxy benzene.
Supporting Information Available: Experimental pro-
cedures and characterization of compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL0354831
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Org. Lett., Vol. 5, No. 22, 2003