Asymmetric cycloetherification based on a chiral auxiliary for 4-acyloxy-1-butene substrates during oxidation with iodosylbenzene via a 1,3-dioxan-2-yl cation

Article abstract of DOI:10.1016/j.tetlet.2009.01.012

Reaction of but-3-enyl camphanate and its derivatives with iodosylbenzene yielded tetrahydrofuran-3-yl camphanate with high diastereomeric ratio via a 1,3-dioxan-2-yl cation intermediate. The reaction using (1S)-camphanate as a chiral auxiliary preferentially gave (S)-3-acyloxytetrahydrofuran and (2S,3S)-3-acyloxy-2-silyltetrahydrofuran.

Full text of DOI:10.1016/j.tetlet.2009.01.012

Tetrahedron Letters 50 (2009) 1298–1300
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Asymmetric cycloetherification based on a chiral auxiliary
for 4-acyloxy-1-butene substrates during oxidation with iodosylbenzene
via a 1,3-dioxan-2-yl cation
*
Morifumi Fujita , Yuuya Ookubo, Takashi Sugimura
Graduate School of Material Science, Himeji Institute of Technology, University of Hyogo, Kohto, Kamigori, Hyogo 678-1297, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Reaction of but-3-enyl camphanate and its derivatives with iodosylbenzene yielded tetrahydrofuran-3-yl
camphanate with high diastereomeric ratio via a 1,3-dioxan-2-yl cation intermediate. The reaction using
(1S)-camphanate as a chiral auxiliary preferentially gave (S)-3-acyloxytetrahydrofuran and (2S,3S)-3-
acyloxy-2-silyltetrahydrofuran.
Received 4 December 2008
Revised 20 December 2008
Accepted 8 January 2009
Available online 10 January 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Tetrahydrofuran
Neighboring group participation
Iodosylbenzene
Hypervalent iodine
Chiral auxiliary
Development of highly stereoselective construction of substi-
tuted tetrahydrofurans as enantiomerically pure form is of great
interest because many biologically active compounds have such
oxygen heterocycles.1,2 Enantiomerically pure tetrahydrofurans
were prepared by a combination of stereoselective reaction steps
in many cases, for example, asymmetric epoxidation followed by
diastereoselective cycloetherification.1 In this Letter, we describe
asymmetric synthesis of optically active tetrahydrofuran during
oxidation of acyloxybutenes with hypervalent iodine(III).3,4 The
reaction has an advantage of stereoselectively forming two stereo-
genic centers at the 2,3-position of tetrahydrofuran in a single step
from alkene substrates.5
the stereoselectivity in the cycloetherification described in this
Letter.
A series of chiral but-3-enyl carboxylates 1a–e were prepared
and subjected to reaction with iodosylbenzene in the presence of
BF3ÁOEt2 in dichloromethane (Table 1). The reaction gave a diaste-
reomeric mixture of 3-acyloxytetrahydrofuran, R-2 and S-2. The
diastereomeric ratio of the product 2 was determined by GLC or
1H NMR (600 MHz).6,7 The camphanate of 1e induced highest dia-
stereoselectivity among the chiral auxiliaries employed.
In order to examine further improvement of the stereoselectiv-
ity, derivative substrates 1e–g with the camphanate auxiliary were
subjected to the diastereo-differentiating tetrahydrofuranylation
We recently found that the tetrahydrofuranylation with hyper-
valent iodine(III) proceeded via a 1,3-dioxan-2-yl cation intermedi-
ate. The intermediate was generated by nucleophilic participation
of the internal acyloxy group of acyloxyalkene substrates during
electrophilic attack of hypervalent iodine(III) toward the substrate
(Scheme 1).5 The cyclic structure of the intermediate cation con-
tributed to the stereoselective preparation of 2,3,5-trisubstituted
tetrahydrofurans.5a An enantio-differentiating variant of the reac-
tion using a lactate-derived hypervalent iodine(III) resulted in
moderate enantioselectivity (up to 64% ee).5b A chiral auxiliary
was introduced as the acyloxy group of the substrate to improve
I+Ph
PhIO
BF3·OEt2
X
R
O
X
O
O
O
R
X = H, SiEt3
O
H
H
O
X
O
O
R
* Corresponding author. Tel.: +81 791 58 0170; fax: +81 791 58 0115.
E-mail address: fuji@sci.u-hyogo.ac.jp (M. Fujita).
Scheme 1. Cycloetherification via a 1,3-dioxan-2-yl cation.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.01.012

M. Fujita et al. / Tetrahedron Letters 50 (2009) 1298–1300
1299
Table 1
Table 2
Chiral auxiliary screening for tetrahydrofuranylationa
Camphanate as a chiral auxiliary in tetrahydrofuranylationa
PhIO
R
R
O
R
R
O
O
BF3·OEt2
O
O
R
S
O
O
+
+
S
R*
O
O
R
O
R*
O
R*
O
PhIO
CH2Cl2
R*
O
R*
O
O
1
R-2
BF3·OEt2
S-2
X
X
X
R-2
R*
O
S-2
CH2Cl2
O
O
Ph
R
1
R
O
Ph
R* =
R* =
R* =
R* =
O
R* =
O
X
R*
O
O
OMe
Me
O
R
3
R
a
c
e : R = H, X = H
f : R = Me, X = H
b
d
e
R* =
O
Entry
Subst.
Temp (°C)
Yield (%)
R-2:S-2
g : R = H, X = SiEt3
1
2
3
1ab
1bb
1c
1d
1d
1e
À30
À40
À40
À40
À40
0
55
57
40
23
46
39
37
55
9:11c,d
1:1c,d
OMe
O
44:56e
60:40e
54:46e
29:71e
23:77e
23:77e
O
4
5f
6
I(OAc)2
4
7
1e
1e
À40
R-2:S-2b
8f
À40
Entry
Subst.
Yield (%)
a
2
3
The reaction was typically carried out in dichloromethane (8 mL) containing a
9c
1e
1e
1f
51
0
0
0
0
77
0
4:96
5:95
substrate (0.4 mmol), PhIO (0.8 mmol), and BF3ÁOEt2 (1.6 mmol) for 1–2 h.
b
10c,d
11
55
81
60f
3
40
49
Racemic 1 was employed for the reaction.
c
The diastereomeric ratio was determined by 1H NMR.
Stereochemistry of 2 was not determined.
The diastereomeric ratio was determined by GLC equipped with a TC-1 column.
47:53e
27:73e
8:92g
<3:97g
<3:97g
d
12c
13
1f
e
1g
1g
1g
f
14d
15c,d
(Hydroxy(tosyloxy)iodo)benzene was employed in place of iodosylbenzene.
0
a
The reaction was typically carried out in dichloromethane (8 mL) containing
substrate (0.4 mmol), PhIO (0.8 mmol), and BF3ÁOEt2 (1.6 mmol) at À40 °C for 1-2 h.
(Table 2). Reaction conditions were also optimized for enhance-
ment of stereoselectivity; optically active (R)-methyl 2-(2-(diacet-
oxyiodo)phenoxy)propanoate 45b was employed for the reaction of
1e (entries 9 and 10). The double asymmetric induction resulted in
higher stereoselectivity (92% de of S-2e). The (R)-reagent 4 prefer-
entially gave (S)-3-benzoyloxytetrahydrofuran with 46% ee in the
reaction of achiral but-3-enyl benzoate.5b Enantioface-differentia-
tion in the simple asymmetric cycloetherification similarly works
for preferential formation of S-2e in the double asymmetric
induction.
b
The diastereomeric ratio was determined by GLC equipped with a TC-1 column
unless otherwise noted.
c
An optically active reagent 4 was employed in place of iodosylbenzene.
A hypervalent iodine reagent was treated with p-toluenesulfonic acid, and the
d
(hydroxy(tosyloxy)iodo)arene obtained was employed for the reaction instead of
iodosylbenzene.
e
Stereochemistry of 2 was not determined.
f
Substrate 1f was recovered in 13% yield.
g
The diastereomeric ratio was determined by 1H NMR.
ethylsilyl)tetrahydrofuran was obtained as enantiomerically pure
form in 77% yield.11
The reaction of dimethyl-substituted substrate 1f gave high
yield of tetrahydrofuran product 2f (entry 11), but the diastereose-
lectivity was poor (53:47). Introduction of the dimethyl group may
accelerate the cyclization by the Trope–Ingold effect to give the
product in high yield.8 Double asymmetric induction in the tetra-
hydrofuranylation of 1f using 4 improved the diastereoselectivity
(entry 12).
The reaction with a silyl-substituted substrate 1g gave a small
amount of tetrahydrofuran product 2g together with a consider-
able amount of a-silyl ketone 3g (entry 13). The yield of 2g was in-
To obtain further insight into the diastereo-differentiating
mechanism, some experiments were carried out. Does diastereose-
lective decomposition of the tetrahydrofuran product affect the
product distribution? Treatment of a 50:50 mixture of R-2e and
S-2e with BF3ÁOEt2 (23 mmol dmÀ3) in dichloromethane at 0 °C
for 4 h resulted in slight change in the diastereomeric ratio of the
recovered 2 (R-2e:S-2e = 48:52). When the reaction of 1e was
quenched at the point when half of substrate 1e remained, the dia-
stereomeric ratio was 25:75 (=R-2e:S-2e). The ratio was similar to
that of the completed reaction (R-2e:S-2e = 23:77 in entry 7).
These results suggest that diastereo-differentiating decomposition
of the tetrahydrofuran products is not a major factor of the diaste-
reomeric ratio of the stereoselective tetrahydrofuranylation of 1e.
The diastereo-differentiation caused by the camphanate moiety
is discussed using theoretical calculations. For the stereo-induced
cycloetherification of pent-4-enyl carboxylates, the stereoselectiv-
ity is rationalized by thermodynamic stability of a 1,3-dioxan-2-yl
cation intermediate.5a Theoretical calculations were carried out for
discussing thermodynamic stability between diastereomers of a
camphanate-derived dioxanyl cation intermediate. 4-Methyl-1,3-
dioxan-2-yl cations were calculated as a model intermediate in
place of 4-(phenyliodonio)methyl-1,3-dioxan-2-yl cations (see
Supplementary data). Diastereomeric difference in energy of the
creased by using a (hydroxyl(tosyloxy)iodo)arene reagent (entries
14 and 15). Under these conditions, a 1,3-dioxan-2-yl cation inter-
mediate may effectively be trapped with water to prevent the 1,2-
elimination pathway giving the
a
-silyl ketone 3g.5a–c Diastereo-
meric ratio of the tetrahydrofuran product 2g was high even in
the reaction with an achiral reagent; only the (3S)-isomer S-2g
was obtained (entry 14).9 The preferential formation of (3S)-con-
figuration agrees with the stereoselectivity in the reaction of a sim-
ple butenyl camphanate 1e. Stereodifferentiation by the
camphanate auxiliary may sterically be enhanced by the silyl sub-
stituent. The silyl-substituted tetrahydrofuran products R-2g and
S-2g have a 2,3-cis configuration, and no 2,3-trans-product was ob-
served.10 The stereospecific formation of the 2,3-cis-product from
the (E)-substrate was observed in the reaction of achiral acyloxy
substrates5c as well, and was rationalized by anti-participation of
the acyloxy group and ensuing SN2 in the departure of the phenyli-
odonio group.5c The chiral auxiliary of S-2g was readily removed by
hydrolysis under basic conditions, and (2S,3S)-3-hydroxy-2-(tri-
camphanate-derived dioxanyl cation was small (0.11 kcal molÀ1
)
at the level of B3LYP/6-31G(d), and was not consistent with the
diastereoselectivity of the tetrahydrofuranylation. Thus, it is neces-

1300
M. Fujita et al. / Tetrahedron Letters 50 (2009) 1298–1300
2003, 125, 11472–11473; (d) Akindele, T.; Marsden, S. P.; Cumming, J. G. Org.
Lett. 2005, 7, 3685–3688; (e) Mertz, E.; Tinsley, J. M.; Roush, W. R. J. Org. Chem.
2005, 70, 8035–8046; (f) Wysocki, L. M.; Dodge, M. W.; Voight, E. A.; Burke, S.
D. Org. Lett. 2006, 8, 5637–5640.
sary to estimate the steric effect of camphanate in the transition
state including the participation of the internal camphanate. Alter-
native explanation for the stereoselectivity is intramolecular inter-
action between the oxy group of camphanate and iodonio group of
the actual intermediate, but this seems unlikely because of high
strain of the interaction.
3. (a) Varvoglis, A. The Organic Chemistry of Polycoordinated Iodine; VCH: New
York, 1992; (b) Varvoglis, A. Hypervalent Iodine in Organic Synthesis; Academic
Press: San Diego, 1997; (c)Hypervalent Iodine Chemistry; Wirth, T., Ed.;
Springer: Berlin, 2003.
4. For recent reviews, see: (a) Varvoglis, A. Tetrahedron 1997, 53, 1179–1255; (b)
Wirth, T.; Hirt, U. H. Synthesis 1999, 1271–1287; (c) Zhdankin, V. V.; Stang, P. J.
Chem. Rev. 2002, 102, 2523–2584; (d) Moriarty, R. M. J. Org. Chem. 2005, 70,
2893–2903; (e) Wirth, T. Angew. Chem., Int. Ed. 2005, 44, 3656–3665; (f)
Richardson, R. D.; Wirth, T. Angew. Chem., Int. Ed. 2006, 45, 4402–4404; (g)
Ochiai, M. Chem. Record 2007, 7, 12–23.
5. (a) Fujita, M.; Suzawa, H.; Sugimura, T.; Okuyama, T. Tetrahedron Lett. 2008, 49,
3326–3329; (b) Fujita, M.; Okuno, S.; Lee, H. J.; Sugimura, T.; Okuyama, T.
Tetrahedron Lett. 2007, 48, 8691–8694; (c) Fujita, M.; Lee, H. J.; Sugimura, T.;
Okuyama, T. Chem. Commun. 2007, 1139–1141; For a related paper, see: (d)
Fujita, M.; Lee, H. J.; Okuyama, T. Org. Lett. 2006, 8, 1399–1401.
6. An authentic sample of S-2 was prepared by esterification of (S)-3-
hydroxytetrahydrofuran (TCI).
In summary, the (1S)-camphanate auxiliary promotes a highly
stereoselective cycloetherification giving (S)-3-acyloxytetrahydro-
furan and (2S,3S)-3-acyloxy-2-silyltetrahydrofuran.
Acknowledgment
This work was partially supported by KAKENHI (19550050)
from Japan Society for the Promotion of Science (JSPS).
Supplementary data
7. If epimerization at the
a-position of the carboxylate of 1a–c (2a–c) took place
during the reaction, diastereomeric ratio should be affected. No experimental
examination for the epimerization was carried out. The poor diastereomeric
ratio obtained is not suitable for asymmetric synthesis whether it takes place
or not.
Supplementary data associated with this Letter can be found, in
the online version, at doi:10.1016/j.tetlet.2009.01.012.
8. (a) Kirby, A. J. In Advances in Physical Organic Chemistry; Gold, V., Bethell, D.,
Eds.; Academic Press: London, 1980; Vol. 17, pp 183–278; (b) Jager, J.;
Graafland, T.; Schenk, H.; Kirby, A. J.; Engberts, J. B. F. N. J. Am. Chem. Soc. 1984,
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9. Absolute stereochemistry of 2g was determined by chiral HPLC analyses of the
benzoate given by transesterification of the 2g obtained from 1g; only (2S,3S)-
3-benzoyloxy-2-(triethylsilyl)tetrahydrofuran5b was detected by HPLC
equipped with a chiral column (Daicel chiralpak AD).
10. Relative stereochemistry of 2g was determined by 1H NMR (600 MHz) in
comparison with that of an authentic sample. The authentic sample was
prepared by transesterification of cis-3-benzoyloxy-2-(triethylsilyl)tetra-
hydrofuran, which was obtained by the reaction of (E)-4-(triethylsilyl)but-3-
enyl benzoate.5c
11. Enantiomeric purity of the hydroxytetrahydrofuran was determined by HPLC
analysis (Daicel chiralpak AD column) of cis-3-benzoyloxy-2-(triethylsilyl)
tetrahydrofuran derived from the hydroxytetrahydrofuran.