Stereoinduced cyclization of acyloxyalkenes using iodosylbenzene via a 1,3-dioxan-2-yl cation

Article abstract of DOI:10.1016/j.tetlet.2008.03.010

Reactions of pent-4-en-2-yl carboxylates and their derivatives with iodosylbenzene gave 2,4-disubstituted and 2,3,5-trisubstituted tetrahydrofurans with high diastereomeric ratio. The tetrahydrofuranylation may proceed via a 1,3-dioxan-2-yl cation intermediate generated by the participation of the internal acyloxy group in electrophilic attack of hypervalent iodine(III) toward acyloxyalkenes. Steric regulation owing to the cyclic structure of the cation accounts for the high stereoselectivity of the tetrahydrofuranylation.

Full text of DOI:10.1016/j.tetlet.2008.03.010

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Tetrahedron Letters 49 (2008) 3326–3329
Stereoinduced cyclization of acyloxyalkenes using
iodosylbenzene via a 1,3-dioxan-2-yl cation
Morifumi Fujita *, Hiroshi Suzawa, Takashi Sugimura, Tadashi Okuyama
Graduate School of Material Science, Himeji Institute of Technology, University of Hyogo, Kohto, Kamigori, Hyogo 678-1297, Japan
Received 8 February 2008; revised 4 March 2008; accepted 5 March 2008
Available online 8 March 2008
Abstract
Reactions of pent-4-en-2-yl carboxylates and their derivatives with iodosylbenzene gave 2,4-disubstituted and 2,3,5-trisubstituted
tetrahydrofurans with high diastereomeric ratio. The tetrahydrofuranylation may proceed via a 1,3-dioxan-2-yl cation intermediate
generated by the participation of the internal acyloxy group in electrophilic attack of hypervalent iodine(III) toward acyloxyalkenes.
Steric regulation owing to the cyclic structure of the cation accounts for the high stereoselectivity of the tetrahydrofuranylation.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Tetrahydrofuran; Neighboring group participation; Iodosylbenzene; Hypervalent iodine
(Diacetoxyiodo)benzene and its derivatives are practi-
cally useful organohypervalent iodine(III) reagents for
oxidation of various functionalities owing to their
environmentally friendly nature and high selectivity.1,2
They undergo oxidative O-3 and N-cyclizations4 of p-elec-
tron donors to yield heterocyclic products through radical
and polar mechanisms. Stereoselective cyclization has been
achieved through a radical mechanism by the reactions
with organohypervalent iodine(V) reagents,5 while there
are few examples of diastereoselective O- and N-cycli-
zations using organoiodine(III) in a polar mechanism;
Spirocyclization of arenes proceeded with high diastereo-
selectivity,3e,4g and intramolecular ene reaction of hydrazide
giving d-lactam resulted in a diastereomeric ratio of 3:1.4a
We have recently found that the reaction of but-3-enyl
carboxylates with iodosylbenzene in the presence of
BF3ÁOEt2 gave 3-acyloxytetrahydrofurans.6 The internal
acyloxy group may participate in the electrophilic addition
of iodine(III) to the C–C double bond in an anti fashion to
give a 1,3-dioxan-2-yl cation intermediate. We envisaged
that the stereoface-selectivity of the electrophilic addition
of iodine(III) would be controlled by the stereogenic center
at the remote 3-position owing to the intermediary forma-
tion of the six-membered ring as illustrated in Scheme 1.
On this stage of tetrahydrofuranylation, 1,3- and 1,4-stereo-
induction (Tables 1 and 2) would be achieved to provide
2,3,5-trisubstituted tetrahydrofurans in a diastereoselective
manner.
Pent-4-en-2-yl carboxylates 1 were subjected to the reac-
tion with iodosylbenzene in the presence of BF3ÁOEt2 in
dichloromethane (Table 1). The reaction gave 4-acyloxy-
2-methyltetrahydrofuran 2 as a diastereomeric mixture.
1,4-induction
PhIO
O
X
O
BF3·OEt2
X
O
I+Ph
R
O
R
X = H, SiEt3
1,3-induction
O
RCOO
X
*
Corresponding author. Tel.: +81 791 58 0170; fax: +81 791 58 0115.
Scheme 1. Stereocontrol via a 1,3-dioxan-2-yl cation.
E-mail address: fuji@sci.u-hyogo.ac.jp (M. Fujita).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.03.010

M. Fujita et al. / Tetrahedron Letters 49 (2008) 3326–3329
3327
The high selectivity7 of the 1,3-stereoinduction suggests
that the nucleophilic addition of the internal acyloxy group
takes place synchronously with the electrophilic addition of
iodine(III) to the double bond. The cyclic structure of the
1,3-dioxan-2-yl cation may make the 1,3-stereoinduction
effective. If the electrophilic addition of iodine(III) pro-
ceeded independently of the nucleophilic participation of
the internal acyloxy group, the iodine reagent should differ-
entiate the diastereoface of the acyclic alkene.
Table 1
Reaction of pent-4-en-2-yl carboxylates
PhIO
BF3·OEt2
O
O
O
+
+
R
O
1
CH2Cl2
RCOO
trans-2
RCOO
1a : R = Ph
cis-2
b : R = CH2Ph
O
O
c : R = 3,5-(CF3)2C6H3
R
O
d : R = 4-MeOC6H4
3
In order to demonstrate advantages of the 1,3-stereoin-
duction due to the cyclic cation intermediate, oxidation of
1a with m-chloroperbenzoic acid (mcpba) was carried out
in the presence of BF3ÁOEt2 at 0 °C (Scheme 3). The reac-
tion with mcpba also gave the tetrahydrofuran product 2a,
but the diastereomeric ratio was 1:1 of trans-2a and cis-2a.
The reaction with mcpba proceeds via epoxides, and the
diastereomeric outcome must be fated before the participa-
tion of the acyloxy group. The stepwise reaction of 1a to 2a
via the epoxide also resulted in a low selectivity; Epoxida-
tion of 1a gave a 4:6 diastereomeric mixture of epoxides,
which was treated with BF3ÁOEt2 to give trans-2a and
cis-2a in a ratio of 4:6. The rearrangement of the epoxide
may stereospecifically proceed via a bicyclic ortho ester
as reported previously.8 Thus, the high stereoselectivity of
the electrophilic attack of iodine(III) toward 1 may be
attributed to the cyclic cation intermediate generated by
the participation of the acyloxy group.9
The diastereoselectivities observed for the substrates
with different acyloxy groups are also consistent with the
participation mechanism of the internal acyloxy group in
the stereo-determining step. Nucleophilicity of the acyloxy
moiety of 1b and 1c is lower than that of 1a and 1d. The
decrease in the nucleophilicity should increase the activa-
tion energy for the formation of the 1,3-dioxan-2-yl cation,
and thus, enhance the difference in energy of the transition
states leading to the cis- and trans-1,3-dioxan-2-yl cations.
In our previous reports,6b the tetrahydrofuranylations
of (E)- and (Z)-4-(triethylsilyl)but-3-enyl carboxylates
stereospecifically gave cis- and trans-3-acyloxy-2-(triethyl-
silyl)tetrahydrofurans, respectively. Thus, introduction
of a silyl group at the terminal vinylic position of
substrate 1 would provide the route to the corresponding
Subst.
Temp. (°C)
trans-2/cis-2/3a
Yieldb (%)
2 (trans/cis)c
3
1a
1a
1b
1b
1c
1c
1d
1d
a
0
À78
0
58:22:20
90:9:1
61:31:8
95:2:3
60:20:20
90:0:10
65:17:18
85:10:5
49 (73:27)
72 (90:10)
52 (64:36)
61 (97:3)
44 (75:25)
69 (>98:2)
48 (79:21)
71 (89:11)
8
2
8
3
À78
0
À78
0
À78
Product distribution of the crude products.
Isolated yield.
Values in parentheses are the ratio of trans-2/cis-2.
b
c
The diastereoselectivity depends on the reaction tempera-
ture and also on the structure of the acyloxy group. The
reaction of the benzoyloxy substrate 1a gave a mixture of
trans-2a/cis-2a with the ratio of 7:3 at the reaction temper-
ature of 0 °C, and the diastereoselectivity improved at
À78 °C to be 9:1. The phenylacetoxy (1b) and bis(trifluoro-
methyl)benzoyloxy (1c) substrates gave higher diastereo-
meric ratios at À78 °C.
Preferential formation of the trans-tetrahydrofuran is
compatible with stability of the 1,3-dioxan-2-yl cation
intermediate (Scheme 2). The trans product is generated
from the cis isomer of the 1,3-dioxan-2-yl cation, in which
the substituents at the 4- and 6-positions mainly take an
equatorial orientation. One of the two substituents at the
4- and 6-positions is forced to an axial orientation in
the case of the trans-1,3-dioxan-2-yl cation that provides
the minor cis-2.
PhIO
BF3·OEt2
O
O
mcpba
O
R
H2O
I+Ph
O
O
I+Ph
BF3·OEt2
O
R
O
1
O
O
+
O
Ph
O
R
H
CH2Cl2
0 ºC
1a
PhCOO
trans-2a
PhCOO
cis-2a
R
OH
O
O
CH2Cl2
0 C
51 : 49
mcpba
O
O
O
º
O
R
I+Ph
I+Ph
I+Ph
R
BF3·OEt2
CH2Cl2
O
43 : 57
77% yield
O
R
O
41% yield
4 : 6
º
0 C
cis-2
trans-2
Scheme 2. Stereochemical outcome of tetrahydrofuranylation.
Scheme 3. Tetrahydrofuranylation via epoxides.

3328
M. Fujita et al. / Tetrahedron Letters 49 (2008) 3326–3329
2,3,5-trisubstituted tetrahydrofurans. The reaction of
(E)-5-(triethylsilyl)pent-4-en-2-yl carboxylates (4) with
iodosylbenzene gave two isomers out of the four possible
3-acyloxy-5-methyl-2-silyltetrahydrofurans, 5, 6, 7, and 8,
together with a-silyl ketone 9 (Table 2). The two tetra-
hydrofurans 5 and 6 obtained from (E)-4 have the 2,3-
cis-configuration. This stereochemistry is rationalized by
anti participation of the acyloxy group in the electrophilic
attack of iodine(III) and the ensuing SN2 in the departure
of the phenyliodonio group, and is in complete agreement
with the stereospecific reaction of (E)-4-(triethylsilyl)but-3-
enyl carboxylates. The major isomer 5 is derived from the
preferred 4,6-di-equatorial dioxanyl cation, and minor 6
is from the axial form. The sense of stereochemical out-
comes of the trisubstituted tetrahydrofurans is compatible
with that of 2.
The reaction of (Z)-4e preferentially gave diastereomer
7e of 3,5-trans- and 2,3-trans-configurations. The 3,5-
trans-configuration may be attributed to the preferential
formation of the di-equatorial dioxanyl cation, and the
2,3-trans-configuration results from the (Z)-configuration
of the substrate. Proton NMR (600 MHz) analyses of the
crude products provided no sign of the fourth diastereomer
8e, which is expected to be obtained as a minor isomer as
discussed above. The reaction of (Z)-4e gave an unexpected
isomer 5e, which is the major isomer obtained from the E
substrate. The formation of 5 from the Z substrate can
be explained by a slight loss of the stereoselectivity in the
last step forming the tetrahydrofuran ring of 7 owing to
partial contribution of SN1 to the departure of the phenyl-
iodonio group.10
In the reaction of silyl-substituted substrate 4, consider-
able amount of a-silyl ketone 9 was obtained as a side
product, which may form via 1,2-elimination of the 1,3-
dioxan-2-yl cation. The formation of 9 was reduced by
replacing the benzoyloxy group in 4a with an acetoxy
group (4e) and by the reaction in the presence of water
(TsOH). The acceleration of trapping of the dioxanyl
cation with water may suppress the 1,2-elimination to pro-
mote the formation of tetrahydrofuran products. Under
these optimized conditions, effective and stereoselective
formation of the silyl-substituted tetrahydrofurans11 was
achieved.
In summary, 1,3- and 1,4-stereoinduction have been
achieved in oxidative tetrahydrofuranylation of acyloxy-
alkenes with iodosylbenzene. The stereoselectivity is well
controlled by the stereochemistry of the 1,3-dioxan-2-yl
cation intermediate.
Acknowledgment
This work was partially supported by KAKENHI
(19550050) from Japan Society for the Promotion of
Science (JSPS).
Table 2
Reaction of 5-silylpent-4-en-2-yl carboxylates
O
O
+
O
O
Supplementary data
SiEt3
PhIO
RCOO
SiEt3
SiEt3
R
R
O
RCOO
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2008.03.010.
5
6
(E)-4
BF3·OEt2
CH2Cl2
O
O
+
O
RCOO
SiEt3
RCOO
SiEt3
References and notes
SiEt3
(Z)-4
8
7
a : R = Ph
e : R = Me
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47
34
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b
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was employed in place of iodosylbenzene.

M. Fujita et al. / Tetrahedron Letters 49 (2008) 3326–3329
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