Stereoselective synthesis of 2,3,5-substituted tetrahydrofurans by silicon-directed cyclization of allylsilanes bearing a hydroxy moiety

Article abstract of DOI:10.1055/s-1998-1888

Acid promoted cyclization of bishomoallylic alcohols bearing allylsilanes proceeded smoothly by way of β-silyl carbocation intermediate to furnish tetrahydrofurans highly stereoselectively.

Full text of DOI:10.1055/s-1998-1888

1150
LETTERS
SYNLETT
Stereoselective Synthesis of 2,3,5-Substituted Tetrahydrofurans by Silicon-Directed
Cyclization of Allylsilanes Bearing a Hydroxy Moiety
*
Takahiko Akiyama and Yuhsuke Ishida
Department of Chemistry, Faculty of Science, Gakushuin University, 1-5-1, Mejiro, Toshima-ku, Tokyo 171-8588, Japan
Fax +81-3-5992-1029; E-mail: takahiko.akiyama@gakushuin.ac.jp
Received 23 June 1998
Acid promoted cyclization of bishomoallylic alcohols
bearing allylsilanes proceeded smoothly by way of β-silyl carbocation
experiments as shown in Figure 1. The corresponding cis isomer was
not detected by 400 MHz H NMR analysis.
Abstract:
1
intermediate to furnish tetrahydrofurans highly stereoselectively.
It is well recognized that a silyl group stabilizes β-silyl carbocation by
1
σ-π conjugation, and numerous kinds of synthetic reactions, which
2
take advantage of the effect, have been developed. Although these
reactions usually proceed by way of desilylation of the β-silyl cationic
intermediate, nucleophilic attack onto the β-silyl carbocation has
recently attracted attention as a novel method for the formation of
3,4
5,6
carbon-carbon bond as well as carbon-hetero atom bond.
Figure 1
There is currently widespread interest in the stereoselective synthesis of
substituted tetrahydrofurans since tetrahydrofuran units are frequently
7
found in polyether antibiotics. Cyclization of alkenyl alcohols
8
promoted by acid or electrophiles furnished tetrahydrofurans. Silicon-
directed formation of tetrahydrofuran from vinylsilane mediated by
9
10
acid, and those from allylsilane promoted via epoxidation have been
reported recently. As part of our continued interest in the development
of novel synthetic methods utilizing the β-silyl carbenium ion
4p,6,11
species,
we wish to report herein highly stereoselective synthesis
of tetrahydrofurans by internal attack of the hydroxyl moiety to the β-
silyl carbenium ion generated from allylsilane by means of proton acid.
Formation of various tetrahydrofurans was studied by use of 20 mol%
13,14
of p-TsOH in CH Cl and the results are shown in Table 2.
2
2
Scheme 1
Introduction of alkyl group on the carbon bearing hydroxy group
facilitated the cyclization (Entry 1). This result indicates that the
nucleophilicity of the hydroxy group was increased by the presence of
the methyl group. Spirocycles were also obtained smoothly (Entries 5
1
and 8). Furthermore, methallylsilane (R =CH ) underwent cyclization
2
3
much faster than (R=H), which was accounted for by the higher
1
stability of the β-silyl carbocation intermediate derived from
in
2
comparison to that from .
1
Stereochemical outcome of the present cyclization can be rationalized
by considering the stability of the β-silyl carbocation intermediate
(Scheme 2). Thus, 2,3-trans isomer was obtained via β-silyl carbocation
( ) which is more favorable than . To confirm that the present
A
B
cyclization is directed by the silyl group, the cyclization reaction of
5
with p-TsOH was attempted under the same conditions. No cyclization
product was obtained under the identical reaction conditions and the
starting material was recovered quantitatively. It is noted that
1
At the outset, an allylsilane bearing homoallylic alcohol (1a; R =H,
2
3
12
R =R =CH ) was treated with several acids in CH Cl and the results
3
2
2
9
cyclization of present allylsilane is much faster than that of vinylsilane.
are shown in Table 1. p-TsOH was found to be the most effective for the
present cyclization. Although 5 mol% of the acid sufficed for the
smooth cyclization, the desired cyclization product (3a) was
instantaneously obtained in an excellent yield as well as highly
stereoselectively under the influence of 20 mol% of p-TsOH (Entry 1).
Methyl group and silyl moiety turned out to be trans by multiple NOE
Next, oxidative cleavage of the carbon-silicon bond was investigated
15
6b,16
(Scheme 3). Treatment of 3a with t-BuOK in DMSO
at room
17
temperature for 1 h followed by H O in the presence of n-Bu NF at
2
2
4
room temperature for 15 min furnished the corresponding alcohol (6) in
a high yield with retention of the stereochemistry.

October 1998
SYNLETT
1151
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Scheme 2
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Scheme 3
In summary, hydroxy-substituted tetrahydrofurans were prepared highly
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References and Notes
(12) Requisite allylsilanes were readily prepared by the reaction of α-
silyl allyl anion and oxiranes (Scheme 4). A representative result
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Scheme 4
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1
(13) Data for selected compounds follow:
:
H NMR (400 MHz,
3a
CDCl ) δ =7.51-7.48 (m, 2H), 7.37-7.34 (m, 3H), 3.91 (dq, 1H, J=
10.6, 6.0 Hz), 1.82 (dd, 1H, J= 12.3, 7.8 Hz), 1.65 (dd, 1H, J=
12.8, 12.3 Hz), 1.39 (ddd, 1H, J= 12.8, 10.6, 7.8 Hz), 1.19 (s, 3H),
1.18 (s, 3H), 1.13 (d, 3H, J=6.0 Hz), 0.32 (s, 3H), 0.31 (s, 3H).
C NMR (100 MHz, CDCl ) δ = 137.72 (C), 133.75 (CH),
3
13
3
129.12 (CH), 127.81 (CH), 79.45 (C), 77.18 (CH), 43.26 (CH ),
34.90 (CH), 29.40 (CH ), 28.81 (CH ), 22.32 (CH ), 4.20 (CH ),
2
3
3
3
3
4.12 (CH ).
3
1
: H NMR (400 MHz, CDCl ) δ = 7.45-7.42 (m, 2H), 7.31-7.27
(m, 3H), 3.83-3.71 (m, 2H), 3.59 (ddd, 1H, J= 8.1, 8.0, 4.0 Hz),
1.96 (dddd, 1H, J= 12.0, 8.8, 6.8, 4.0 Hz), 1.71 (dddd, 1H, J=
12.0, 11.2, 8.1, 8.1 Hz), 1.07 (d, 3H, J= 6.0 Hz), 1.06-1.01 (m,
1H), 0.26 (s, 3H), 0.25 (s, 3H). C NMR (100 MHz, CDCl ) δ =
3d
3
13
3
137.55 (C), 133.75 (CH), 129.15 (CH), 127.81 (CH), 77.73 (CH),
67.18 (CH ), 33.91 (CH), 30.16 (CH ), 21.69 (CH ), 4.28 (CH ),
2
2
3
3
4.16 (CH ).
3
1
: H NMR (400 MHz, CDCl ) δ = 3.95 (ddd, 1H, J= 7.3, 6.0, 5.9
6
3
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Hz), 3.85 (dq, 1H, J= 6.0, 6.0 Hz), 2.12 (dd, 1H, J= 12.8, 7.3 Hz),
1.76 (dd, 1H, J= 12.8, 5.9 Hz), 1.68 (brs, 1H), 1.35 (s, 3H), 1.27
13
(s, 3H), 1.26 (d, 3H, J= 6.0 Hz). C NMR (100 MHz, CDCl ) δ =
3

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SYNLETT
80.10 (CH), 79.88 (C), 77.94 (CH), 47.08 (CH ), 30.30 (CH ),
the crude mixture by column chromatography (SiO , hexane:
2
3
2
28.88 (CH ), 19.24 (CH ).
ethyl acetate = 12:1, v/v) gave 3a (57.9 mg, 89%).
3
3
(14) A typical experimental procedure for the preparation of 3a is
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Fleming, I. Eds.; Pergamon Press: Oxford, 1991; Vol. 7; p 641.
Jones, G. R.; Landais, Y. Tetrahedron 1996, 52, 7599. Fleming, I.
Chemtracts-Org. Chem. 1996, 9, 1. Tamao, K. Adv. Silicon Chem.
1996, 3, 1.
described (entry 1, Table 2). To predried p-TsOH•H O (11 mg,
2
0.052 mmol) was added a solution of 1a (65 mg, 0.26 mmol) in
CH Cl (0.7 ml) at room temperature. After being stirred at the
2
2
temperature for 20 min, the reaction was quenched by addition of
water. The aqueous layer was extracted with ethyl acetate and the
combined organic layers were washed with brine, dried over
(16) Murakami, M.; Suginome, M.; Fujimoto, K.; Nakamura, H.;
Andersson, P. G.; Ito, Y. J. Am. Chem. Soc. 1993, 115, 6487.
anhydrous Na SO , and concentrated to dryness. Purification of
2
4
(17) Tamao, K.; Ishida, N.; Kumada, M. J. Org. Chem. 1983, 48, 2120.
Tamao, K.; Ishida, N. J. Organomet. Chem. 1984, 269, C37.