3-Silyloxytetrahydrofurans via sulfoxonium ylide reactions with α-silyloxyepoxides

Article abstract of DOI:10.1016/j.tetlet.2007.09.113

α-Silyloxyepoxides were found to undergo sulfoxonium ylide induced ring-opening, followed by silyl-migration and intramolecular S_N2 reaction, resulting in 3-silyloxytetrahydrofurans. Studies on the scope and utility of this transformation are d

Full text of DOI:10.1016/j.tetlet.2007.09.113

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Tetrahedron Letters 48 (2007) 8356–8359
3-Silyloxytetrahydrofurans via sulfoxonium ylide reactions
with a-silyloxyepoxides
Paul S. Sabila, Yanke Liang and Amy R. Howell*
Department of Chemistry, University of Connecticut, Storrs, CT 06269-3060, United States
Received 4 July 2007; revised 7 September 2007; accepted 18 September 2007
Available online 21 September 2007
Abstract—a-Silyloxyepoxides were found to undergo sulfoxonium ylide induced ring-opening, followed by silyl-migration and intra-
molecular SN2 reaction, resulting in 3-silyloxytetrahydrofurans. Studies on the scope and utility of this transformation are described.
Ó 2007 Elsevier Ltd. All rights reserved.
In the accompanying paper we describe the conversion
of a-mesyloxyoxetanes to 2-alkylidene oxetanes by a
base promoted 1,2-elimination.1 The alkylidene oxetane
precursors were prepared by sulfoxonium ylide medi-
ated ring expansion of protected a-hydroxyepoxides.
During that investigation it became apparent that the
success of this expansion for accessing a-hydroxyoxe-
tanes was dependent on the presence and nature of the
protecting group on the OH moiety. With benzyl protec-
tion, as described in the accompanying paper, hydroxy-
oxetane 4a was obtained in good yield after cleavage of
the benzyl group. In the absence of a protecting group
or with a silyl group a different outcome was observed,
as is described here.
Initially, ring expansion with unprotected a-hydroxy-
epoxide 1a was attempted (Scheme 1). The major prod-
uct was the corresponding tetrahydrofuran (THF) 3a,
rather than oxetane 4a. In retrospect, the outcome was
not surprising, as under the strongly basic conditions
dialkoxide 2a would be an intermediate, and cyclization
to the 5-membered THF ring would be favored over
oxetane formation. Consequently, the a-hydroxy moiety
was protected with a TBDMS group to give 1b. When
OR
O
O-
S
I
S(O)(CH3)2
Ph
Ph
Ph
O
O-
t
-BuOK,
t
-BuOH
1a R = H
1b R = TBDMS
(R = H)
2a
not
O
OR
O
S
I
Ph
4a R = H
4b R = TBDMS
t
-BuOK,
t
-BuOH
OR
O
3a R = H
3b R = TBDMS
(R = TBDMS)
O-
OTBDMS
S(O)(CH3)2
S(O)(CH3)2
Ph
Ph
O-
OTBDMS
2b
2b
Scheme 1.
*
Corresponding author. E-mail: amy.howell@uconn.edu
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.09.113

P. S. Sabila et al. / Tetrahedron Letters 48 (2007) 8356–8359
8357
a. Borhan's approach to 2,3-disubstituted THF's from α-hydroxyepoxides
OH
O-
O
S
O-
,
n
-BuLi
I
O
O
S(O)(CH3)2
OH
R
R
THF, -78 oC - rt
3
R
R
O-
OH
5
6
7
O
R
R = Ph, vinyl
OH
b. 3,4-Disubstituted THF's from α-silyloxyepoxides
8
OH
CH2S(O)(CH3)2
CH2S(O)(CH3)2
O
S
O
I
R
O-
OTBDMS
R
OTBDMS
R
conditions
R
O-
OTBDMS
OTBDMS
9
8
Figure 1. Disubstituted THF’s from epoxides with vicinal oxygenation.
this was treated with dimethylsulfoxonium methylide,
silyl-protected THF 3b resulted (60% yield, 1:1 mixture
of diastereomers), rather than the desired oxetane.
Again, with hindsight the silyl migration was not sur-
Table 1. Reactions of a-silyloxyepoxides with dimethylsulfoxonium methylide
Epoxide
Condition
Product
Yield (%)
70
O
TBDMSO
TBDMSO
BnO
O
OTBDMS
1
TBDMSO
9
21
22
OTBDMS
OTBDMS
TBDMSO
TBDMSO
O
2
72
O
10
1 or 2
NR
O
11
OTBDMS
BnO
TBDMSO
O
2
44
O
12
23
OTBDMS
C4H9
TBDMSO
1 or 2
NR
O
13
OTBDMS
OTBDMS
O
2
50
O
14
TBDMSO
24
1 or 2
NR
O
15
I
I
OTBDMS
25
15
3
49
78
OH
OTBDMS
9
3
OH
26
Conditions: (1) (CH3)3SOI, t-BuOK, t-BuOH; (2) (CH3)3SOI, n-BuLi (6–10 equiv), 24–32 h; (3) (BF3ÆOEt2) + epoxide followed by addition of
preformed ylide.

8358
P. S. Sabila et al. / Tetrahedron Letters 48 (2007) 8356–8359
prising2,3 However, we decided to explore the scope and
utility of this silyl-migratory entry to 3-silyloxy-THF’s.
1.
OTBDMS
n
-BuLi; CH3SO2Cl,
HO
OTBDMS
THF, -78 oC
2. LiAlH4, THF, -78 oC
(65%, two steps)
20
19
Subsequent to this initial observation of the conversion
of a-silyloxyepoxide 1b to 3-silyloxy-THF 3b, Borhan
and co-workers reported the conversion of epoxyalco-
hols 5 to 2,3-disubstituted THF’s 7 in the presence of
excess dimethylsulfoxonium methylide (Fig. 1a).4 This
process exploited the enhanced reactivity of epoxides
6, formed by Payne rearrangement of 5, and is attractive
because of the ease of asymmetric synthesis of the chiral
epoxides 5 and because of the stereoselectivity of the
transformation. Yields were best when the ‘R’ group
contained an a-oxygen; simple alkyl groups resulted in
more complex product mixtures and low yields of 7
because of competing reaction by the ylide at C3 of
epoxyalcohols 5. In fact, 3,4-disubstituted-THF’s 8 were
isolated as the major product, albeit in modest yields
(30–50%) when R was phenyl or vinyl. We recognized
that the conversion of 5 to 7 was similar to our initial
result, as the intermediates 6 correspond to our starting
epoxides 1, and the number of steps to access 3b is iden-
tical using the chemistry in Scheme 1 or following the
silylation of 7 (if R = PhC2H4). However, neither our
initial studies nor Borhan’s work provided an effective
synthesis of 3,4-disubstituted THF’s 8. Here we describe
our progress toward this goal (see Fig. 1b), which
requires regioselective attack of dimethylsulfoxonium
methylide on a 1,2-disubstituted epoxide.
DMDO
CH2Cl2, 95%
OTBDMS
O
14
Scheme 3.
THF (condition 2 in Table 1). As anticipated, the simple
model glycidol-derived epoxide 9 underwent smooth
conversion to 3-silyloxy-THF 21. The cis,bis-TBDMS
protected epoxide 10 reacted stereospecifically with
similar efficiency to provide 3,4-disubstituted THF 22,
while the corresponding trans-isomer 11 did not react.
Differentially protected epoxide 12 gave THF 23.
Although the yield was lower than for the formation
of 22, compound 23 was the major product, and no
other product was identifiable. The more sterically
encumbered cis,bis-silyl epoxide 13 did not undergo
reaction with the sulfoxonium ylide generated under
either condition 1 or 2. With cis-epoxide 14, having only
single a-oxygenation, ring expansion gave 24 in mode-
rate yield, with no readily identifiable by-products. As
with trans-epoxide 11 versus cis-isomer 10, the trans-dia-
stereomer 15 of 14 did not react with the sulfoxonium
ylide.
A series of epoxides, shown in Table 1, was prepared to
probe scope and utility of the silyl-migratory pathway to
the functionalized THF’s, especially 3,4-disubstituted-
THF’s. The epoxides were chosen to look at the effects
of both stereochemistry and substituents on reaction
outcome. Racemic epoxides 9,5 10,6,7 11,8 12,9,10 and
1511 are known compounds. Epoxide 13 was prepared
from known aldehyde 16,12 as shown in Scheme 2.
Nucleophilic addition of n-butyllithium provided allyl
alcohol 17. Epoxidation gave an approximately 1:1 mix-
ture of diastereomers 18, which was protected to provide
doubly silylated epoxide 13. cis-Epoxide 14 was pre-
pared by oxidation of TBDMS-protected alcohol 20,
available from the reduction13 of known,14 monopro-
tected diol 19 (Scheme 3).
Attempts to effect the desired reaction by Lewis acid
(BF3ÆOEt2) activation of the epoxide (15 or 9) gave
iodohydrins (25 or 26, respectively), rather than THF’s.
The outcome was the same whether the (BF3ÆOEt2) was
added to the epoxide prior to addition of the ylide or
added to the reaction mixture subsequent to combining
all the other reagents. Moreover, varying the number of
equivalents of (BF3ÆOEt2) did not substantially alter the
results. Attempts to scavenge the iodide counterion sub-
sequent to generating the ylide were unsuccessful. Use of
trimethysulfoxonium chloride, containing the less nucleo-
philic chloride counterion, as the source of the sulfoxo-
nium ylide, resulted in the corresponding chlorohydrin.
These results suggest that the Lewis basicity of the ylide
would complicate any efforts to use Lewis acids to acti-
vate the epoxides.
The epoxides were reacted with dimethylsulfoxonium
methylide, either generated in situ by reaction of tri-
methylsulfoxonium iodide with potassium t-butoxide
in t-butanol (condition 1 in Table 1) or preformed by
treatment of the sulfoxonium iodide with n-BuLi in
We also investigated the outcome with a silyloxy group
beta to the epoxide. Known b-hydroxyoxirane 2715 was
silylated (Scheme 4); the resultant b-silyloxyoxirane 28
HO
CH3CO3H
n
-BuLi, THF
89%
TBDMSO
TBDMSO
O
TBDMSO
C4H9
NaOAc, CHCl3
85%
16
17
OH
OTBDMS
C4H9
TBDMSCl, Imidazole
CH2Cl2, 92%
C4H9
TBDMSO
O
O
13
18
Scheme 2.

P. S. Sabila et al. / Tetrahedron Letters 48 (2007) 8356–8359
8359
O
TBDMSCl,
OTBDMS
Ph
OH
O
O
S
I
Imidazole, DMAP
t
-BuOK,
t-BuOH
Ph
CH2Cl2, 78%
28
27
91%
not seen
O
Ph
TBDMSO
O
Ph
OTBDMS
29
30
Scheme 4.
was then reacted with dimethylsulfoxonium methylide,
generated by treatment of trimethylsulfoxonium iodide
with potassium t-butoxide in t-butanol. Oxetane 29
was isolated in excellent yield, and no pyran formation
(30) was seen, indicating that 1,5-silyl-migration did
not compete with oxetane formation.
References and notes
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dimethylsulfoxonium methylide. trans-Epoxides fail to
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Acknowledgement
This manuscript is based upon work supported by the
National Science Foundation (NSF) under Grant No.
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Supplementary data
Full experimental procedures and characterization data
are provided as supplementary data. Supplementary
data associated with this article can be found, in the on-
line version, at doi:10.1016/j.tetlet.2007.09.113.
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