Acid-catalyzed cyclization of vinylsilanes bearing a hydroxy group: A new method for stereoselective synthesis of disubstituted tetrahydrofurans

Article abstract of DOI:10.1021/ja002496q

In the presence of a catalytic amount of TsOH or TiCl₄, (Z)-5-silyl-4-penten-1-ols ((Z)-1) are smoothly cyclized to 2-silylmethyl-substituted tetrahydrofurans. This cyclization is applicable to the construction of a tetrahydropyran ring. The silyl group and the geometry of the C-C double bond strongly influence the cychzation rate. TBDMS and benzyldimethylsilyl groups considerably accelerate the cyclization in comparison with a dimethylphenylsilyl group, and (E)-vinylsilanes show much lower reactivity than the corresponding (Z)-isomers. The cyclization proceeds by stereospecific syn addition of the hydroxy group. Vinylsilanes 17, 19, and 21, (Z)-5-silyl-4-penten-1-ols bearing a substituent on the methylene tether, smoothly undergo the acid-catalyzed cyclization to give trans-2,5-, cis-2,4-, and trans-2,3-disubstituted tetrahydrofurans, respectively, with moderate to high stereoselectivity. The silyl group of some cychzed products can be easily converted into a hydroxy group with stereochemical retention.

Full text of DOI:10.1021/ja002496q

11348
J. Am. Chem. Soc. 2000, 122, 11348-11357
Acid-Catalyzed Cyclization of Vinylsilanes Bearing a Hydroxy
Group: A New Method for Stereoselective Synthesis of Disubstituted
Tetrahydrofurans1
Katsukiyo Miura, Shigeo Okajima, Takeshi Hondo, Takahiro Nakagawa,
Tatsuyuki Takahashi, and Akira Hosomi*
Contribution from the Department of Chemistry, Graduate School of Pure and Applied Sciences,
UniVersity of Tsukuba, Tsukuba, Ibaraki 305-8571, Japan
ReceiVed July 10, 2000
Abstract: In the presence of a catalytic amount of TsOH or TiCl4, (Z)-5-silyl-4-penten-1-ols ((Z)-1) are smoothly
cyclized to 2-silylmethyl-substituted tetrahydrofurans. This cyclization is applicable to the construction of a
tetrahydropyran ring. The silyl group and the geometry of the C-C double bond strongly influence the cyclization
rate. TBDMS and benzyldimethylsilyl groups considerably accelerate the cyclization in comparison with a
dimethylphenylsilyl group, and (E)-vinylsilanes show much lower reactivity than the corresponding (Z)-isomers.
The cyclization proceeds by stereospecific syn addition of the hydroxy group. Vinylsilanes 17, 19, and 21,
(Z)-5-silyl-4-penten-1-ols bearing a substituent on the methylene tether, smoothly undergo the acid-catalyzed
cyclization to give trans-2,5-, cis-2,4-, and trans-2,3-disubstituted tetrahydrofurans, respectively, with moderate
to high stereoselectivity. The silyl group of some cyclized products can be easily converted into a hydroxy
group with stereochemical retention.
Introduction
electrophilic unsaturated bonds are highly efficient in the
stereoselective synthesis of carbocycles and heterocycles.5,6 On
the other hand, vinylsilanes have been rarely used as precursors
of â-silylcarbenium ions for C-C and C-heteroatom bond
(6) Recent papers on [3 + 2] cycloadditions of allylsilanes: (a) Peng
Z.-H.; Woerpel, K. A. Org. Lett. 2000, 2, 1379. (b) Roberson, C. W.;
Woerpel, K. A. J. Org. Chem. 1999, 64, 1434. (c) Kno¨lker, H.-J.; Jones, P.
G.; Wanzl, G. Synlett 1998, 613. (d) Akiyama, T.; Hoshi, E.; Fujiyoshi, S.
J. Chem. Soc., Perkin Trans. 1 1998, 2121. (e) Akiyama, T.; Yamanaka,
M. Tetrahedron Lett. 1998, 39, 7885. (f) Groaning, M. D.; Brengel, G. P.;
Meyers, A. I. J. Org. Chem. 1998, 63, 5517.
(7) Other reactions via â-silylcarbenium ions generated from allyl-
silanes: (a) Sugimura, H. Tetrahedron Lett. 1990, 31, 5909. (b) Kiyooka,
S.; Shiomi, Y.; Kira, H.; Kaneko, Y.; Tanimori, S. J. Org. Chem. 1994,
59, 1958. (c) Akiyama, T.; Nakano, M.; Kanatani, J.; Ozaki, S. Chem. Lett.
1997, 385. (d) Brocherieux-Lanoy, S.; Dhimane, H.; Poupon, J.-C.; Vanucci,
C.; Lhommet, G. J. Chem. Soc., Perkin Trans. 1 1997, 2163. (e) Monti,
H.; Rizzotto, D.; Le´andri, G. Tetrahedron 1998, 54, 6725. (f) Akiyama,
T.; Ishida, Y.; Kagoshima, H. Tetrahedron Lett. 1999, 40, 4219. (g) Sugita,
Y.; Kimura, Y.; Yokoe, I. Tetrahedron Lett. 1999, 40, 5877. (h) Angle, S.
R.; El-Said, N. A. J. Am. Chem. Soc. 1999, 121, 10211.
The stereoselective synthesis of substituted cyclic ethers is
an important and attractive subject in organic synthesis since
cyclic ether units are frequently found in polyether antibiotics
and other biologically active natural products.2 Cyclization of
alkenyl alcohols is a straightforward route to the cyclic skeletons.
In general, a Brønsted acid or an electrophilic heteroatom
reagent (e.g., Br2, I2, Pd(II) salts, etc.) is known to promote the
process when the C-C double bond is not activated by an
electron-withdrawing group.3 The acid-catalyzed cyclization is
rather limited in its applicability.4 In contrast, the electrophile-
initiated reaction provides a powerful method for the synthesis
of highly functionalized cyclic ethers, although it is not
necessarily effective for highly stereoselective synthesis. There
is still a need for a new method realizing high levels of
efficiency and stereoselectivity in the synthetic route to cyclic
ethers from alkenyl alcohols.
(8) (a) Brook, M. A.; Sebastian, T.; Jueschke, R.; Dallaire, C. J. Org.
Chem. 1991, 56, 2273. (b) Brook, M. A.; Henry, C.; Jueschke, R.; Modi,
P. Synlett 1993, 97. (c) Yamazaki, S.; Tanaka, M.; Yamaguchi, A.; Yamabe,
S. J. Am. Chem. Soc. 1994, 116, 2356. (d) Yamazaki, S.; Tanaka, M.;
Yamabe, S. J. Org. Chem. 1996, 61, 4046.
The development of new synthetic methods utilizing nucleo-
philic addition to â-silylcarbenium ions is of considerable current
interest.5-14 Particularly, the Lewis acid-promoted [3 + 2]
cycloadditions of allylsilanes and the related compounds to
(9) It is known that â-silylcarbenium ions generated from vinylsilanes
react with a halide ion to form a carbon-halogen bond. (a) Sommer, L.
H.; Bailey, D. L.; Goldberg, G. M.; Buck, C. E.; Bye, T. S.; Evans, F. J.;
Whitmore, F. C. J. Am. Chem. Soc. 1954, 76, 1613. (b) Koenig, K. E.;
Weber, W. P. Tetrahedron Lett. 1973, 2533. (c) Miller, R. B.; McGarvey,
G. J. Org. Chem. 1978, 43, 4424.
(10) (a) Hosomi, A. Acc. Chem. Res. 1988, 21, 200. (b) Hojo, M.; Tomita,
K.; Hirohara, Y.; Hosomi, A. Tetrahedron Lett. 1993, 34, 8123. (c) Hojo,
M.; Ishibashi, N.; Ohsumi, K.; Miura, K.; Hosomi, A. J. Organomet. Chem.
1994, 473, C1. (d) Hojo, M.; Murakami, C.; Aihara, H.; Tomita, K.; Miura,
K.; Hosomi, A. J. Organomet. Chem. 1995, 499, 155.
(11) For preliminary papers on this work, see: (a) Miura, K.; Okajima,
S.; Hondo, T.; Hosomi, A. Tetrahedron Lett. 1995, 36, 1483. (b) Miura,
K.; Hondo, T.; Okajima, S.; Hosomi, A. Tetrahedron Lett. 1996, 37, 487.
(12) Related work: (a) Miura, K.; Hondo, T.; Saito, H.; Ito, H.; Hosomi,
A. J. Org. Chem. 1997, 62, 8292. (b) Miura, K.; Hondo, T.; Nakagawa, T.;
Takahashi, T.; Hosomi, A. Org. Lett. 2000, 2, 385. (c) Miura, K.; Hondo,
T.; Takahashi, T.; Hosomi, A. Tetrahedron Lett. 2000, 41, 2129.
(1) Organosilicon Chemistry. 153. For part 152, see: Ito, H.; Yajima,
T.; Tateiwa, J.; Hosomi, A. Chem. Commun. 2000, 981.
(2) Reviews: (a) Boivin T. L. B. Tetrahedron 1987, 43, 3309. (b)
Kotsuki, H. Synlett 1992, 97. (c) Harmange, J.-C.; Figade`re, B. Tetra-
hedron: Asymmetry 1993, 4, 1711. (d) Koert, U. Synthesis 1995, 115.
(3) (a) Larock, R. C.; Leong, W. W. In ComprehensiVe Organic
Synthesis; Trost, B. M., Ed.; Pergamon Press: Oxford, 1991; Vol. 4, p 269.
(b) Harding, K. E.; Tiner, T. H. In ComprehensiVe Organic Synthesis; Trost,
B. M., Ed.; Pergamon Press: Oxford, 1991; Vol. 4, p 363 and references
therein. (c) Cardillo, G.; Orena, M. Tetrahedron 1990, 46, 3321.
(4) (a) Watanabe, S.; Suga, K.; Fujita, T.; Takahashi, Y. Synthesis 1972,
422. (b) Pellicciari, R.; Castagnino, E.; Fringuelli, R.; Corsano, S.
Tetrahedron Lett. 1979, 20, 481.
(5) For reviews: (a) Panek, J. S. In ComprehensiVe Organic Synthesis;
Trost, B. M., Ed.; Pergamon Press: Oxford, 1991; Vol. 1, p 579. (b) Masse,
C. E.; Panek, J. S. Chem. ReV. 1995, 95, 1293. (c) Kno¨lker, H.-J. J. Prakt.
Chem. 1997, 339, 304.
10.1021/ja002496q CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/03/2000

Cyclization of Vinylsilanes Bearing a Hydroxy Group
J. Am. Chem. Soc., Vol. 122, No. 46, 2000 11349
Scheme 1
tetrahydrofuran 2b and hardly suffered desilylation to 4 (entry
2). Thus, the present cyclization does not require a bulky silyl
group to achieve high efficiency, in contrast with the Lewis
acid-promoted cycloaddition of allylsilanes.14
TiCl4 served as an effective catalyst for this cyclization, even
at 25 °C (entry 3). Other Lewis acids such as SnCl4 and BF3‚
OEt2 showed little catalytic ability because of fast desilylation
to 4. AcCl also induced the cyclization of (Z)-1a at 25 °C (entry
4). In this case, HCl generated by the reaction of AcCl with the
hydroxy group would be the actual catalyst.15 There is a
possibility that TiCl4 also works as a HCl source. However,
TiCl4 has a higher catalytic activity than AcCl. In addition, the
TiCl4-catalyzed cyclization in the presence of di-tert-butyl-
pyridine (5 mol %) as a proton scavenger gave 2a in 88% yield,
although the reaction took a prolonged time (18 h) to reach
completion. From these observations, it is probable that TiCl4
itself is the actual catalyst.
The reaction rate is strongly dependent on the silyl group
and the geometry of the C-C double bond. Introduction of a
TBDMS or benzyldimethylsilyl (BnDMS) group effectively
increased the cyclization rate (entries 5-7). The Z-isomer of
1a is more reactive than its E-isomer in both catalyst systems
with TsOH and TiCl4 (entries 1, 3 vs 8, 9). In the initial period
(within 3 h) of the TsOH-catalyzed cyclization, the yield of 2a
was directly proportional to the reaction time, and (Z)-1a was
cyclized 2.7 times (k ) slope, kZ/kE ) 2.7) faster than (E)-1a.
The rate difference with the TiCl4 catalyst was remarkable
compared to that with the TsOH catalyst, although the relation-
ship between the yield and the reaction time was not in direct
proportion (see Supporting Information).
Both isomers of vinylsilane 6 bearing a longer methylene
tether by one carbon also underwent the acid-catalyzed cycliza-
tion to afford the corresponding tetrahydropyran 7, although
they showed lower reactivity than 1a (entries 10-13). TsOH
was superior to TiCl4 in catalytic activity, which is quite
different from the observation with 1a. We also attempted to
apply the present method to the construction of seven-membered
cyclic ethers. However, the TsOH-catalyzed cyclization of
vinylsilane 8 was rather slow and afforded oxepane 9 in poor
yield (entry 14).
To confirm that the acid-catalyzed cyclization is directed by
the silyl group, control experiments using alkenols 10 were
carried out under the same conditions. As a result, no cyclized
products were obtained, and the substrates were recovered intact.
Stereochemical Aspect. The stereochemistry of the present
intramolecular addition of a hydroxy group was investigated
with deuterium-labeled (Z)- and (E)-vinylsilanes 11 and 14 (98%
D, Z:E or E:Z ) >98:2, Table 2). Cyclization of (Z)- and (E)-
11 afforded diastereomeric mixtures of tetrahydrofurans 12 and
13 with inverse stereochemistry (entries 1-4).16 This result
indicates that syn addition of the hydroxy group to the C-C
double bond is favored over anti addition. Both isomers of
vinylsilane 14 were also cyclized to tetrahydropyrans 15 and
16 with high levels of syn addition (entries 5-8). The observed
stereochemistry stands in sharp contrast to the stereospecific
anti addition in electrophile-initiated cyclofunctionalization.3b
A plausible mechanism for the stereospecific syn addition is
as follows (Scheme 2, X ) D): (1) attachment of a proton or
TiCl4 to the hydroxy group of (Z)-11 or (Z)-14 forms oxonium
Table 1. Acid-Catalyzed Cyclization of Vinylsilanes 1, 6, and 8a
entry substrate catalyst temp/°C time/h product yield/%
1
2
(Z)-1a
(Z)-1b
(Z)-1a
(Z)-1a
(Z)-1c
(Z)-1d
(Z)-1d
(E)-1a
(E)-1a
(Z)-6
TsOH
TsOH
TiCl4
AcCl
TiCl4
TsOH
TiCl4
TsOH
TiCl4
TsOH
TiCl4
TsOH
TiCl4
TsOH
60
60
25
25
25
60
25
60
25
60
60
60
60
60
10
5
2a
2b
2a
2a
2c
2d
2d
2a
2a
7
94
64b (92)c
92
3
3
4
12
1.2
2.75
0.75
25
25
96
96
96
96
85
86
5
85b
97
6
7
96
8
91
9
61
10
11
12
13
14
86
(Z)-6
7
71
(E)-6
7
64
(E)-6
7
29
(Z)-8
9
17
a All reactions were carried out with a substrate (1.0 mmol) and a
catalyst (0.05 mmol) in CHCl3 (5 mL). b The lower yield is due to
volatility of the product. c The yield in parentheses was determined by
1H NMR analysis of a crude product.
formation.8,9 In the course of our studies on silicon-directed
synthetic reactions,10 we have found that vinylsilanes bearing a
hydroxy group are easily cyclized to tetrahydrofurans and
tetrahydropyrans in the presence of an acid catalyst.11-13
A
plausible mechanism for this cyclization involves the formation
of a â-silylcarbenium ion intermediate by protonation of the
sp2 carbon R to the silyl group and the subsequent intramolecular
attack of the hydroxy oxygen to the carbenium ion center. We
report herein the scope and mechanistic aspects of the silicon-
directed cyclization and its application to the stereoselective
synthesis of disubstituted tetrahydrofurans.11
Results and Discussion
Acid-Catalyzed Cyclization of Vinylsilanes 1, 6, and 8.
Treatment of dimethylphenylvinylsilane (Z)-1a (Z:E ) >98:2)
with a catalytic amount of TsOH‚H2O in CHCl3 at 60 °C gave
tetrahydrofuran 2a in 94% yield, along with a mixture of (Z)-
1a (3%), (E)-1a (0.3%), allylsilane 3 (0.9%), and 4-penten-1-
ol (4, 0.3%) (Scheme 1 and entry 1 in Table 1). The formation
of these products indicates that the acid-catalyzed reaction
proceeds via â-silylcarbenium ion intermediate 5 generated by
protonation of the C-C double bond. Trimethylvinylsilane (Z)-
1b as well was efficiently cyclized to the corresponding
(15) We have reported that HCl gas as well as AcCl catalyzes the 1,2-
silyl-migrative cyclization of vinylsilanes bearing a hydroxy group. See
ref 12a.
(16) The relative configurations of 12, 13, 15, and 16 were determined
by comparison of their 1H NMR spectra with the spectra of their authentic
samples which were prepared by the stereodefined methods. See Supporting
Information.
(13) Related work by other groups: (a) Akiyama, T.; Ishida, Y. Synlett
1998, 1150; 1999, 160 (Errata). (b) Adiwidjaja, G.; Flo¨rke, H.; Kirschning,
A.; Schaumann, E. Liebigs Ann. 1995, 501.
(14) Kno¨lker, H.-J.; Foitzik, N.; Goesmann, H.; Graf, R. Angew. Chem.,
Int. Ed. Engl. 1993, 32, 1081.

11350 J. Am. Chem. Soc., Vol. 122, No. 46, 2000
Table 2. Cyclization of Deuterated Vinylsilanes 11 and 14a
Miura et al.
Scheme 3
entry substrate catalyst temp/°C time/h yield/% 12:13 or 15:16b
1
2
3
4
5
6
7
8
(Z)-11
(Z)-11
(E)-11
(E)-11
(Z)-14
(Z)-14
(E)-14
(E)-14
TsOH
TiCl4
TsOH
TiCl4
TsOH
TiCl4
TsOH
TiCl4
60
25
60
25
60
60
60
60
10
4
94
94
92
60
81
68
69
30
83:17
91:9
13:87
12:88
94:6
92:8
12:88
16:84
25
25
96
96
96
96
a See footnote a in Table 1. b The ratio was determined by 1H NMR
analysis. See ref 16 for the stereochemical assignment.
rotamers C1 and C2 are enantiomers of C2′ and C1′, respec-
tively, the rotation of C1′ to C2′ (C1 to C2) is equivalent to
that of C2 to C1 (C2′ to C1′). Accordingly, the formation of
anti adducts from Z- and E-substrates suggests the presence of
the rotation interconverting C1 and C2 (C1′ and C2′) as a minor
reaction path. Intermolecular protonation (path b) directly
forming B (B′) is also possible. However, the path including
steps 1 and 2 (path a) provides a reasonable explanation for the
low reactivity of 6 and the stereochemical outcomes in the
diastereoselective cyclization (vide infra).
Scheme 2
To obtain an insight into the reversibility of the protonation
step (from A to C1), the TsOH-catalyzed cyclization of (Z)-11
(98% D) was stopped before it reached completion (2 h, 67%
conversion of (Z)-11, 61% yield of 12 and 13, 12:13 ) 85:15).
The recovered substrate retained almost all the deuterium label
as well as the (Z)-configuration (97% D, Z:E ) >98:2). This
observation shows that â-silylcarbenium ion C2 is hardly
converted into dedeuterated (Z)-vinylsilane; therefore, the rever-
sion of C1 to (Z)-11 is also unlikely. The configurational
retention discloses that the formation of anti adduct 13 is not
due to the cyclization of (E)-11 generated by the acid-catalyzed
isomerization of (Z)-11.
The rate difference between Z- and E-isomers suggests that
step 2 is the rate-determining step,12 because steps 1 and 4
should not be influenced by the geometry of substrates, and
step 3 would be much faster than the other steps. The enhanced
cyclization rate with 1c and 1d is probably a result of the fact
that the electron-donating ability of the TBDMS and BnDMS
groups facilitates step 2 by raising the HOMO level of the C-C
double bond.18 The high reactivity of the Z-isomer is attributable
to steric repulsion between the silyl group and the methylene
tether, which would also accelerate step 2. Another possible
explanation, particularly in the cyclization of (Z)-1, is that allylic
1,3-strain caused by the silyl group induces A (n ) 1) to take
chairlike conformation D that is requisite for step 2.19 The lower
reactivity of 6 compared with that of 1 would arise from the
difficulty of intramolecular protonation of A (n ) 2) with a
longer methylene tether.
ion A; (2) the proton on the oxygen atom shifts to the R-carbon;
(3) the resultant â-silylcarbenium ion B immediately turns to
its rotamer C1, stabilized by σ-π conjugation at the least
motion;17 (4) intramolecular attack of the hydroxy oxygen from
the side opposite to the silyl group gives syn adduct 12 or 15
and regenerates the acid catalyst. Similarly, the reaction of (E)-
11 or (E)-14 proceeds through A′, B′, and C1′ to give syn adduct
13 or 16. Minor anti adduct would be formed by cyclization of
another stabilized rotamer C2 (C2′) arising from C1 (C1′). Since
Stereoselective Synthesis of Disubstituted Tetrahydro-
furans. The present silicon-directed cyclization is considerably
efficient in the construction of tetrahydrofurans. Therefore, our
efforts were directed toward the stereoselective synthesis of
disubstituted tetrahydrofurans using (Z)-vinylsilanes 17, 19, and
21 (Scheme 3).
(17) There is a long-standing dispute over the structure of â-silyl
carbenium ions, which can take a hyperconjugatively stabilized open form
or a bridged form. Although the open forms (C1, C2, C1′, and C2′) are
employed in Scheme 2, they can be easily displaced to the bridged forms.
Lambert, J. B.; Zhao, Y. J. Am. Chem. Soc. 1996, 118, 7867 and references
cited therein.
(18) For the difference between TBDMS and phenyldimethylsilyl
(PDMS) groups in electronic effect, see: Mayr, H.; Patz, M. Angew. Chem.,
Int. Ed. Engl. 1994, 33, 938.
(19) For acceleration of an intramolecular reaction by the increase of
strain energy, see: Beckwith, A. L. J.; Zimmermann, J. J. Org. Chem. 1991,
56, 5791 and references therein.

Cyclization of Vinylsilanes Bearing a Hydroxy Group
J. Am. Chem. Soc., Vol. 122, No. 46, 2000 11351
Table 3. Cyclization of (Z)-1-Substituted 5-Silyl-4-penten-1-ols 17a
substrate
TsOH at 60 °C
TiCl4 at room temperature
entry
R
R1
time/h
yield/%
trans:cisb
time/h
yield/%
trans:cisb
1
2
Ph
Ph
n-C6H13
i-Pr
Ph
Ph
n-C6H13
i-Pr
Ph
n-C6H13
i-Pr
i-Pr
Ph
Ph
17a
17b
17c
8
7
92
95
95
90
90
93
89
76
66
66
93
94
83:17
83:17
89:11
83:17
60:40
81:19
85:15
90:10
89:11
91:9
7
7
89
89
92
88
82
86
73
84
82
68
98
89
89
90:10
86:14
92:8
86:14
66:34
82:18
87:13
96:4
91:9
93:7
88:12
88:12
95:5
Ph
Ph
Me
Me
Me
Me
H
3
6
6
4
17d
(E)-17d
17e
7
7
5
16
8
25
7
6
7
17f
7
7
8
17g
17h
17i
9
7
9
H
H
t-Bu
Bn
Bn
6
7
10
11
12
13
11
2
7
17j
17k
17k
83:17
85:15
0.3
0.7
23c
1.3
a All reactions were carried out with a vinylsilane (1.00 mmol) and TsOH‚H2O (10 mg, 0.05 mmol) or TiCl4 (1.0 M in CH2Cl2, 50 µL, 0.05
1
mmol) in CHCl3 (5 mL). b Determined by H NMR analysis. c At -20 °C.
Table 4. Cyclization of (Z)-2-Substituted 5-Silyl-4-penten-1-ols 19a
substrate
R2
TsOH at 60 °C
TiCl4 at room temperature
entry
R
time/h
yield/%
trans:cisb
time/h
yield/%
trans:cisb
1
2
Ph
Ph
Ph
Me
Me
Me
H
Ph
n-C6H13
i-Pr
19a
19b
19c
19d
19e
19f
19g
19h
19i
11
8
80
97
96
95
96
83
84
78
79
90
18:82
21:79
17:83
18:82
23:77
16:84
16:84
19:81
14:86
17:83
11
9
97
98
97
94
93
82
85
82
72
94
93
14:86
15:85
10:90
13:87
16:84
12:88
9:91
12:88
9:91
16:84
10:90
3
8
9
4
Ph
n-C6H13
i-Pr
Ph
n-C6H13
i-Pr
Ph
Ph
11
10
10
11
7
7
1.5
8
5
7
6
7
7
14
7
8
H
9
H
Bn
Bn
8
10
11
19j
19j
0.7
10c
a,b,c See footnotes a, b, and c in Table 3, respectively.
Table 5. Cyclization of (Z)-3-Substituted 5-Silyl-4-penten-1-ols 21a
substrate
R3
TsOH at 60 °C
TiCl4 at room temperature
entry
R
time/h
yield/%
trans:cisb
time/h
yield/%
trans:cisb
1
2
3
4
5
6
7
Ph
Ph
Me
Me
H
Ph
n-C5H11
Ph
n-C5H11
Ph
n-C5H11
Ph
21a
21b
21c
21d
21e
21f
20
14
8
80
87
79
89
47
34
96
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1d
20
5
70
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
98:2d
93
8
86
90
9
5
14
6
8.5
12
5
65 (84)c
81
H
Bn
21g
7
93
a See footnote a in Table 3. b Determined by 1H NMR analysis. The ratio >99:1 means that no cis isomer is detected by 1H NMR analysis. c The
yield with 10 mol % of TiCl4. d Determined by GC analysis.
As shown in Table 3, cyclization of 17 afforded 2,5-
disubstituted tetrahydrofurans in good to high yields with
moderate to high trans selectivity. The TiCl4-catalyzed system
at room temperature exhibited slightly higher diastereoselectivity
than the TsOH-catalyzed system at 60 °C. The higher selectivity
is probably due to the lower reaction temperature because the
TsOH-catalyzed cyclization of 17d at room temperature for 114
h achieved higher selectivity (88%, trans:cis ) 85:15) than that
at 60 °C (entry 4). The use of (E)-17d revealed that the
E-configuration markedly diminished not only reactivity but also
trans selectivity (entry 5). Introduction of a bulky substituent
(Ph or i-Pr) as R1 is effective in improving the proportion of
the trans isomer. The silyl group also affected the stereoselec-
tivity to some extent. Vinylsilanes 17g-i bearing a dimethylsilyl
group gave the best results in stereoselectivity under the same
reaction conditions (entries 8-10). Unfortunately, the cyclization
of 17g-i resulted in lower yields than that of 17a-c because
of competitive desilylation and Si-H bond cleavage of the
product. The TBDMS and BnDMS groups strongly accelerated
the cyclization, in accordance with the results of (Z)-1c and (Z)-
1d, while they were not effective in improving the diastereo-
selectivity (entries 11, 12). However, the high reactivity of 17k
enabled the cyclization at -20 °C to effect high trans selectivity
(entry 13).
Vinylsilanes 19 bearing a homoallylic substituent (R2) were
cyclized to 2,4-disubstituted tetrahydrofurans 20 with moderate
to high cis selectivity (Table 4). The influence of the reaction
conditions and the substituents R and R2 on the stereoselectivity
is similar to that observed with 17. The TiCl4-catalyzed
cyclization at 25 °C exhibited better syn selectivity than the
TsOH-catalyzed cyclization at 60 °C. The use of hydrogen as
R or a bulky group as R2 slightly improved the syn selectivity.
In this case also, a BnDMS group effectively raised the
cyclization rate, and the cyclization of 19j at -20 °C achieved
high efficiency and stereoselectivity (entries 10, 11).
In most cases, vinylsilanes 21 formed only trans-22 irrespec-
tive of the reaction conditions and the substituents R and R3
unlike 17 and 19 (Table 5). When R3 was a phenyl group, the
yield of 22 was not so high under both reaction conditions except
for the case with 21g (entries 1, 3, 5, and 7). Thus, the BnDMS
group proved to be an effective promoter for the cyclization of
21 as well.

11352 J. Am. Chem. Soc., Vol. 122, No. 46, 2000
Miura et al.
Table 6. Oxidative Cleavage of the Silicon-Carbon Bond of 2-(Silylmethyl)Tetrahydrofuransa
substrate
product
yield/%
entry
R
R1
R2
R3
trans:cisb
method
trans:cisb
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
Ph
Bn
Bn
Bn
Ph
n-C6H13
i-Pr
H
H
H
H
H
Ph
H
H
H
H
Ph
H
H
H
H
H
Ph
n-C5H11
H
H
H
Ph
18g
18h
18i
20g
22e
22f
18a
18k
20j
22g
96:4
86:14
93:7
12:88
>99:1
>99:1
92:8
88:12
15:85
98:2d
A
A
A
A
A
A
B
C
C
C
23a
23b
23c
24
25a
25b
23a
23a
24
93
85
83
90
91
89
59
93
96
55
96:4
87:13c
93:7c
13:87
>99:1
>99:1
90:10
88:12
15:85
95:5d
H
Ph
Ph
H
10
H
25a
a For methods A-C, see the text and the Experimental Section. b Determined by 1H NMR analysis. c Determined by 1H NMR analysis of iodides
26 derived from 23. See Table 7. d Determined by GC analysis.
Table 7. Derivatization of 23 and Iodocyclization of 27 and 28
Oxidative Cleavage of the Silicon-Carbon Bond. It is well
known that some silyl groups are useful as hydroxy surrogates.20
To enhance the synthetic utility of the present cyclization,
oxidative cleavage of the silicon-carbon bond of the cyclized
products was next attempted. As shown in Table 6, each
dimethylsilyl group of 18g-i, 20g, and 22e,f could be easily
converted to a hydroxy group by treatment of H2O2-KHCO3/
THF-MeOH (method A, Tamao’s method)21 with retention of
the stereochemistry (entries 1-6). The conversion of 18a,
bearing a dimethylphenylsilyl group, to alcohol 23a was
achieved by a two-step procedure including pretreatment with
yield of 26/% (trans:cis)a
R1
a: Ph
b: n-C6H13
c: i-Pr
from 23b
from 27
from 28
t-BuOK/DMSO and subsequent oxidation with TBAF-H2O2-
KHCO3/MeOH-THF (method B, entry 7).22 In contrast, the
cyclized products 18k, 20j, and 22g bearing a BnDMS group
were smoothly oxidized to the corresponding alcohols by a one-
step procedure using only the latter set of reagents without the
pretreatment (method C, entries 8-10).12b,c Accordingly, the
BnDMS group is considerably valuable as not only a promoter
of the present cyclization but also a latent hydroxy group.
89 (96:4)
79 (87:13)
82 (93:7)
61 (74:26)
68 (69:31)
66 (81:19)
c
83 (<5:95)
90 (5:95)
a Determined by H NMR analysis. b Derived from 18h (trans:cis
) 96:4), 18i (trans:cis ) 86:14), and 18j (trans:cis ) 93:7). See entries
1-3 in Table 6. c The reaction resulted in a complex mixture of
products, including a small amount of 26a.
1
Stereochemical Assignment. The relative configuration of
2,5-disubstituted tetrahydrofurans can be determined on the basis
of the chemical shifts for the protons at the 2- and 5-positions.23
Due to a 1,3-deshielding effect of an alkyl substituent on the
γ-proton, the signals of H-2 and H-5 of the trans isomers appear
at lower fields than those of the corresponding cis isomers.24
On the basis of this criterion, the major isomers of 18 were
assigned to the trans configuration. This assignment was
ascertained by derivatization of 18. Namely, 18g-i were
converted to iodides 26 with stereochemical retention by
oxidative cleavage of the Si-C bond, tosylation of the resulting
alcohols 23, and subsequent iodination with NaI (Table 7).
Bartlett et al. have reported that iodocyclization of 4-alkenyl
alcohols 27 gives 26 with moderate trans selectivity, while the
reaction of 4-alkenyl 2,6-dichlorobenzyl ethers 28 shows high
cis selectivity.25 The major isomers of iodides 26 derived from
18g-i were identical with those from 27. The observation
proves the major isomers of 18g-i to be trans.
According to Eliel et al., ring carbon atoms C-2, C-3, and
C-4 of the cis isomers of 2,4-disubstituted tetrahydrofurans show
a downfield shift, while the signal of C-5 appears at higher field
compared to that of the trans isomer.26 On the basis of these
criteria, the major isomers of 20 were determined to possess a
cis configuration. This assignment was ascertained by NOE
experiments of the major isomer of 20j. Irradiation of one proton
on C-3 showed considerable enhancements of protons on C-2
(7.3%) and C-4 (7.9%). In contrast, these protons were not so
enhanced upon irradiation of another proton on C-3 (1.8% in
both cases). These observations clearly support the above
assignment. In addition, alcohol 24 derived from 20j was
converted into the deoxygenated form 29 (eq 1), whose major
(20) Reviews: (a) Colvin, E. W. In ComprehensiVe Organic Synthesis;
Trost, B. M., Ed.; Pergamon Press: Oxford, 1991; Vol. 7, p 641. (b) Jones,
G. R.; Landais, Y. Tetrahedron 1996, 52, 7599.
(21) Tamao, K.; Ishida, N. J. Organomet. Chem. 1984, 269, C 37.
(22) Murakami, M.; Suginome, M.; Fujimoto, K.; Nakamura, H.;
Andersson, P. G.; Ito, Y. J. Am. Chem. Soc. 1993, 115, 6487.
(23) Schmitt, A.; Reissig, H.-U. Chem. Ber. 1995, 128, 871.
(24) Anteunis, M.; Danneels, D. Org. Magn. Reson. 1975, 7, 345.
(25) Rychnovsky, S. D.; Bartlett, P. A. J. Am. Chem. Soc. 1981, 103,
3963.
isomer was found to be identical with the authentic sample of
(26) Eliel, E. L.; Rao, V. S.; Pietrusiewicz, K. M. Org. Magn. Reson.
1979, 12, 461.

Cyclization of Vinylsilanes Bearing a Hydroxy Group
J. Am. Chem. Soc., Vol. 122, No. 46, 2000 11353
Table 8. Derivatization of 25 and Iodocyclization of 31
Scheme 4
yield of 30/% (trans:cis)a
R3
a: Ph
b: n-C5H11
from trans-25
from 31
82 (>99:1)
63 (>99:1)
77 (64:36)
90 (57:43)
1
a Determined by H NMR analysis.
cis-29 prepared from methyl phenylacetate (see Supporting
Information).
Scheme 5
For configurational assignment of 22, derivatization of
alcohols 25 to the corresponding iodides 30 and the preparation
of both isomers of 30 from alkenyl alcohols 31 were performed
as described in Table 8. In trans-2,3-disubstituted tetrahydro-
furans, H-2 and H-3 on the ring are shielded by the vicinal C-C
bond, and their signals are observed at higher field than those
of the cis isomers. For the same reason, the 2,3-cis configuration
induces an upfield shift of the alkyl protons of the substitu-
ents.23,24 Additionally, nonbonding interaction arising from the
cis configuration brings C-2, C-3, and R-carbons of the
substituents to higher field.27 Judging from these criteria, the
1H and 13C NMR data for 30 prepared from 25 and 31 show
that the major isomers of 22 have the trans configuration.
Origin of Stereoselectivity. The present cyclization proceeds
by stereospecific syn addition of a hydroxy group, as mentioned
above. This result means that proton transfer (step 2) and
nucleophilic attack of the hydroxy oxygen (step 4) take place
on the same side of the π-face, as shown in Scheme 2.
Accordingly, the relative configuration of products would
depend mainly on diastereoface selection of the proton transfer.
In other words, the observed diastereoselectivity would be
attributed to diastereoface-selective protonation. Considering that
the protonation site is away from the stereogenic center in
vinylsilanes 17 and 19, it is difficult to explain the diastereoface-
selective protonation through intermolecular path b (Scheme
2). Conversely, intramolecular path a, via an oxonium ion
intermediate such as A, can easily rationalize the diastereoface-
selection.
In intramolecular protonation of 17, two transition states
arising from chairlike conformers Ech-eq and Ech-ax are plau-
sible, while boatlike conformers Eb-eq and Eb-ax are strictly
inhibited by an allylic 1,3-strain between the methylene tether
and the silyl group (Scheme 4).28,29 Conformer Ech-ax has a
repulsive nonbonding interaction between R1 and the silyl group,
which makes Ech-ax an energetically unfavorable conformer.
Consequently, the proton transfer would proceed exclusively
via conformer Ech-eq to achieve high levels of diastereoface
selection. The subsequent nucleophilic attack of the hydroxy
oxygen on the same side as the protonation gives trans-18, in
agreement with the present observation.
Scheme 6
the energy difference between Fch-eq and Fb-eq is much smaller
than that between Ech-eq and Eb-eq. In addition, the energy
difference between Fch-eq and Fch-ax is not as large as that
between Ech-eq and Ech-ax because of the absence of a steric
repulsion between R1 and the silyl group. These decreases in
energy difference would cause low diastereoselectivity to (E)-
17d (entry 5 in Table 3).
The stereochemical outcome with 19 can be explained by
considering two conformers, Gch-eq and Gch-ax, in the proto-
nation step (Scheme 6). Since Gch-ax exhibits nonbonding
interactions of R2 with the olefinic hydrogen and lone electron
pair of the hydroxy oxygen, the cyclization of 19 would proceed
mainly via the energetically more favored conformer Gch-eq to
afford cis-20 selectively. Similarly, the high trans selectivity
with 21 is probably due to a large energy difference between
Hch-eq and Hch-ax. The latter conformer has a severe allylic 1,3-
strain between R3 and the silyl group, which would strictly
In the cyclization of (E)-17, four conformers leading to
transition states of intramolecular protonation are conceivable
(Scheme 5). Boatlike conformers Fb-eq and Fb-ax do not have
a severe allylic 1,3-strain as shown in Eb-eq and Eb-ax; therefore,
suppress the cyclization to cis-22 via Hch-ax
.
(27) (a) Accary, A.; Huet, J.; Infarnet, Y.; Duplan, J. C. Org. Magn.
Reson. 1978, 11, 287. (b) Kalinowski, H.-O.; Berger, S.; Braun, S. Carbon-
13 NMR Spectroscopy; Wiley: Chichester, 1988.
As shown in Table 2, the present cyclization includes anti
addition of a hydroxy group as a minor path. The formation of
a minor diastereomer in the cyclization of 17, 19, and 21 is
attributable to anti addition via the chair-equatorial conformer
of an oxonium ion intermediate as well as syn addition via the
(28) Hoffmann, R. W. Chem. ReV. 1989, 89, 1841.
(29) (a) McCormick, M.; Monahan, R., III; Soria, J.; Goldsmith, D.;
Liotta, D. J. Org. Chem. 1989, 54, 4485. (b) Semmelhack, M. F.; Zhang,
N. J. Org. Chem. 1989, 54, 4483.

11354 J. Am. Chem. Soc., Vol. 122, No. 46, 2000
Miura et al.
Scheme 7
promoter. In conclusion, we have demonstrated that the present
cyclization followed by oxidative cleavage of the Si-C bond
is effective for the stereoselective synthesis of a variety of
disubstituted tetrahydrofurans.
Experimental Section
General Method. Unless otherwise noted, all reactions and the
following distillations were carried out under N2. Solvents were dried
by distillation from sodium metal/benzophenone ketyl (THF, Et2O),
CaCl2-NaHCO3 (CHCl3), and CaH2 (DMSO, CH2Cl2). AcCl was
distilled from N,N-dimethylaniline. TiCl4, BF3‚OEt2, and SnCl4 were
simply distilled and stored as a CH2Cl2 solution (1.0 M). All other
commercial reagents were used as received. Na2SO4 was used as the
drying agent for aqueous workup. Boiling points (air-bath temperature)
were determined with Kugelrohr distillation apparatus. 1H and 13C NMR
spectra were recorded in CDCl3 at 270 and 67.7 MHz, respectively.
The chemical shifts (δ) are referenced to 0.00 ppm (Me4Si) or 7.26
ppm (CHCl3) for the proton and to 77.00 ppm (centered on the signal
of CDCl3) for the carbon. 13C NMR data of minor isomers are shown
only for well-resolved signals.
other conformers. The selectivities of (Z)-11 toward syn addition
are 83% with TsOH at 60 °C and 91% with TiCl4 at room
temperature (entries 1 and 2 in Table 2). On the assumption
that the substituent on the methylene tether (R1, R2, or R3)
has no influence on the selectivities, 17a-c, 19a-c, and 21a,b
are expected to show less than 83% (TsOH, 60 °C) or 91%
(TiCl4, room temperature) diastereoselectivity. However, some
observed stereoselectivities are higher than these values (entry
3 in Table 3; entries 1 and 2 in Table 5). This inconsistency
indicates that the above assumption is not reasonable and there
is a secondary factor controlling the diastereoselectivity, other
than the diastereoface-selective intramolecular proton transfer.
Based on the mechanism shown in Scheme 2, the reaction
path from 21 to trans- and cis-22 would include oxonium ion
H, â-silylcarbenium ion I, and its rotamer J as intermediates
(Scheme 7). An equilibrium between I and J is also conceivable,
although it is not as fast as the ring closure of I. The
intermediates I and J should take chairlike conformations Ich-eq
and Jch-ax for the ring closure, forming trans- and cis-22,
respectively. In this situation, the ring closure of J is expected
to be much slower than that of I because of the pseudoaxial
substituent R3 in Jch-ax. The decreased cyclization rate, which
can cause isomerization of J to I and desilylation of J, would
be a secondary reason for the high trans selectivity with 21. A
similar explanation is applicable for the stereochemical outcomes
with 17 and 19.
Acid-Catalyzed Cyclization of Vinylsilanes (Typical Procedure).
Vinylsilane (Z)-1a (220 mg, 1.00 mmol) was added to TsOH‚H2O (10
mg, 0.05 mmol) in CHCl3 (5 mL), and then the mixture was heated to
60 °C. After being stirred for 10 h, the resultant solution was poured
into saturated aqueous NaHCO3 (20 mL). The extract with CH2Cl2
(2 × 20 mL) was dried and evaporated. Purification by column
chromatography (SiO2, hexane-AcOEt 10:1) gave 2-(dimethylphenyl-
silylmethyl)tetrahydrofuran (2a, 208 mg, 94%) along with a mixture
of (E)-5-dimethylphenylsilyl-3-penten-1-ol (3, 0.9%), 4 (0.3%), and
both isomers of 1a (3.3%, Z:E ) 10:1). In the TiCl4-catalyzed
cyclization, a CH2Cl2 solution of TiCl4 (0.05 mL, 0.05 mmol) was added
to 1a (220 mg, 1.00 mmol) in CHCl3 (5 mL). After completion of the
reaction, the same workup and purification gave 2a (202 mg, 92%).
2a: bp 90 °C (1.0 Torr); IR (neat) 2960, 1249, 1112, 1077, 832,
700 cm-1; 1H NMR δ 0.316 (s, 3H), 0.322 (s, 3H), 1.06 (dd, J ) 14.2,
8.6 Hz, 1H), 1.23-1.38 (m, 2H), 1.74-1.94 (m, 3H), 3.58-3.67 (m,
1H), 3.80-3.93 (m, 2H), 7.32-7.36 (m, 3H), 7.49-7.54 (m, 2H); 13
C
NMR δ -2.46 (CH3), -2.19 (CH3), 23.41 (CH2), 25.88 (CH2), 33.81
(CH2), 66.86 (CH2), 77.05 (CH), 127.66 (CH × 2), 128.79 (CH), 133.45
(CH × 2), 139.07 (C); MS m/z (relative intensity) 220 (M+, 0.3), 137
(100). Anal. Calcd for C13H20OSi: C, 70.68; H, 8.72. Found: C, 70.68;
H, 9.08.
1
3: IR (neat) 3394 (br), 2922, 1427, 1257, 1049 cm-1; H NMR δ
0.28 (s, 6H), 1.25 (br s, 1H), 1.71 (d, J ) 7.9 Hz, 2H), 2.21 (dt, J )
7.3, 6.6 Hz, 2H), 3.52 (br s, 2H), 5.18 (dt, J ) 15.2, 7.3 Hz, 1H), 5.50
(dt, J ) 15.2, 7.9 Hz, 1H), 7.30-7.37 (m, 3H), 7.47-7.54 (m, 2H);
13C NMR δ -3.39 (CH3 × 2), 22.07 (CH2), 36.17 (CH2), 62.16 (CH2),
124.98 (CH), 127.78 (CH × 2), 129.04 (CH), 129.60 (CH), 133.59
(CH × 2), 138.54 (C); MS m/z (relative intensity) 205 (M+ - Me,
0.9), 135 (100); HRMS calcd for C13H20OSi 220.1283, found 220.1279.
2-(Trimethylsilylmethyl)tetrahydrofuran (2b): bp 75 °C (84 Torr);
Conclusion
We have found that vinylsilanes 1 and 6 smoothly undergo
acid-catalyzed cyclization by stereospecific syn addition of the
hydroxy group to give 2-silylmethyl-substituted cyclic ethers.
This silicon-directed reaction proceeds with a catalytic amount
of an acid in high efficiency, even when the substrate has a
relatively small silyl group such as a TMS group. A plausible
mechanism for the present cyclization includes intramolecular
protonation, forming a â-silylcarbenium ion intermediate, and
the subsequent nucleophilic attack of the hydroxy oxygen to
the carbenium ion center. The â-effect of the silyl group not
only accelerates the protonation step but also holds the
conformation of the carbenium ion intermediate to realize the
stereospecific syn addition. The cyclization rate, enhanced by
an electron-donating silyl group and the (Z)-geometry of the
C-C double bond, shows that the intramolecular protonation
is the rate-determining step. Vinylsilanes 17, 19, and 21 are
cyclized to trans-2,5-, cis-2,4-, and trans-2,3-disubstituted
tetrahydrofurans, respectively, with moderate to high levels of
stereoselectivity. The stereochemical outcomes are rationalized
by diastereoface-selective intramolecular proton transfer via a
chairlike conformation bearing an equatorial substituent. The
cyclized products can be converted to the corresponding alcohols
by oxidative cleavage of the Si-C bond. In particular, a BnDMS
group works as a good hydroxy surrogate as well as an effective
1
IR (neat) 2935, 1248, 1112, 860, 835 cm-1; H NMR δ 0.03 (s, 9H),
0.81 (dd, J ) 14.3, 8.9 Hz, 1H), 1.09 (dd, J ) 14.3, 5.6 Hz, 1H),
1.29-1.43 (m, 1H), 1.83-2.02 (m, 3H), 3.65 (ddd, J ) 8.0, 8.0,
6.2 Hz, 1H), 3.82-3.94 (m, 2H); 13C NMR δ -0.914 (CH3 × 3),
24.28 (CH2), 26.04 (CH2), 33.82 (CH2), 66.92 (CH2), 77.49 (CH); MS
m/z (relative intensity) 157 (M+ - H, 1.9), 175 (100). Anal. Calcd for
C8H18OSi: C, 60.69; H, 11.46. Found: C, 60.57; H, 11.17.
2-(tert-Butyldimethylsilylmethyl)tetrahydrofuran (2c): IR (neat)
1
2935, 1462, 1360, 1249, 1078, 827 cm-1; H NMR δ -0.02 (s, 3H),
-0.01 (s, 3H), 0.79 (dd, J ) 14.0, 9.1 Hz, 1H), 0.86 (s, 9H), 1.12 (dd,
J ) 14.0, 4.4 Hz, 1H), 1.23-1.43 (m, 1H), 1.79-2.06 (m, 3H), 3.65
(dt, J ) 6.6, 6.3 Hz, 1H), 3.82-3.95 (m, 2H); 13C NMR δ -5.70 (CH3),
-5.34 (CH3), 16.42 (C), 19.91 (CH2), 26.08 (CH2), 26.37 (CH3 × 3),
33.95 (CH2), 66.90 (CH2), 77.61 (CH); MS m/z (relative intensity) 200
(M+, 0.1), 185 (0.2), 75 (100). Anal. Calcd for C11H24OSi: C, 65.92;
H, 12.07. Found: C, 65.74; H, 12.16.
2-(Benzyldimethylsilylmethyl)tetrahydrofuran (2d): bp 70 °C
(0.17 Torr); IR (neat) 2955, 1591, 1491, 1249 cm-1; 1H NMR δ 0.004
(s, 3H), 0.02 (s, 3H), 0.82 (dd, J ) 14.2, 7.9 Hz, 1H), 1.08 (dd, J )
14.2, 5.9 Hz, 1H), 1.26-1.43 (m, 1H), 1.78-2.03 (m, 3H), 2.12 (s,

Cyclization of Vinylsilanes Bearing a Hydroxy Group
J. Am. Chem. Soc., Vol. 122, No. 46, 2000 11355
1
2H), 3.66 (td, J ) 7.9, 6.6 Hz, 1H), 3.82-3.95 (m, 2H), 6.98-7.09
(m, 3H), 7.17-7.24 (m, 2H);13C NMR δ -2.91 (CH3), -2.82 (CH3),
22.43 (CH2), 25.97 (CH2), 26.13 (CH2), 34.07 (CH2), 67.03 (CH2), 77.14
(CH), 123.94 (CH), 128.14 (CH × 4), 140.09 (C); MS m/z (relative
intensity) 219 (M+ - Me, 0.1), 75 (100). Anal. Calcd for C14H22OSi:
C, 71.73; H, 9.46. Found: C, 71.82; H, 9.19.
2-(Dimethylphenylsilylmethyl)tetrahydropyran (7): bp 95 °C
(0.30 Torr); IR (neat) 2960, 1246, 1112, 1086, 820, 700 cm-1; 1H NMR
δ 0.30 (s, 3H), 0.32 (s, 3H), 0.99 (dd, J ) 14.4, 6.3 Hz, 1H), 1.14 (dd,
J ) 14.5, 7.6 Hz, 1H), 1.22-1.57 (m, 5H), 1.70-1.78 (m, 1H), 3.28-
3.40 (m, 2H), 3.90-3.96 (m, 1H), 7.32-7.36 (m, 3H), 7.49-7.55 (m,
2H); 13C NMR δ -2.36 (CH3), -1.78 (CH3), 23.78 (CH2), 24.61 (CH2),
25.79 (CH2), 35.05 (CH2), 68.29 (CH2), 75.88 (CH), 127.63 (CH ×
2), 128.69 (CH), 133.55 (CH × 2), 139.60 (C); MS m/z (relative
intensity) 234 (M+, 0.4), 219 (M+ - Me, 58), 137 (100), 135 (100).
Anal. Calcd for C14H22OSi: C, 71.73; H, 9.46. Found: C, 71.53; H,
9.48.
824, 697 cm-1; H NMR δ 0.32-0.33 (s × 3, 6H), 1.09-1.22 (m,
1H) including 1.13 (dd, J ) 14.2, 8.3 Hz), 1.35-1.58 (m, 2H), 1.70-
1.84 (m, 1H), 1.88-2.07 (m, 1H), 2.17-2.38 (m, 1H), 4.02-4.12 (m,
0.15H), 4.27 (tt, J ) 8.3, 5.9 Hz, 0.85H), 4.77 (dd, J ) 7.3, 6.9 Hz,
0.15H), 4.96 (dd, J ) 8.4, 6.4 Hz, 0.85H), 7.15-7.37 (m, 8H), 7.49-
7.55 (m, 2H); 13C NMR for major isomer δ -2.35 (CH3), -2.01 (CH3),
24.12 (CH2), 35.35 (CH2), 35.71 (CH2), 77.74 (CH), 79.46 (CH), 125.43
(CH × 2), 126.83 (CH), 127.73 (CH × 2), 128.19 (CH × 2), 128.88
(CH), 133.57 (CH × 2), 139.12 (C), 144.29 (C), for minor isomer δ
-2.01 (CH3), 23.91 (CH2), 33.77 (CH2), 34.76 (CH2), 77.20 (CH), 77.81
(CH), 125.71 (CH × 2), 128.00 (CH), 128.12 (CH × 2), 128.57 (CH),
143.68 (C); MS m/z (relative intensity) 296 (M+, 0.8), 281 (M+ - Me,
4), 135 (100). Anal. Calcd for C19H24OSi: C, 76.97; H, 8.16. Found:
C, 77.13; H, 8.20.
2-Dimethylphenylsilylmethyl-5-hexyltetrahydrofuran
(18b,
trans:cis ) 86:14): IR (neat) 2920, 1248, 1109, 838, 822, 727, 699
cm-1; H NMR δ 0.307 (s, 3H), 0.314 (s, 3H), 0.88 (t, J ) 6.6 Hz,
1
2-(Dimethylphenylsilylmethyl)oxepane (9): IR (neat) 2925, 1247,
1116, 836, 699 cm-1; 1H NMR δ 0.30 (s, 3H), 0.32 (s, 3H), 0.99 (dd,
J ) 14.8, 5.6 Hz, 1H), 1.17 (dd, J ) 14.8, 8.6 Hz, 1H), 1.40-1.82 (m,
8H), 3.38 (ddd, J ) 12.2, 7.6, 4.0 Hz, 1H), 3.60 (dddd, J ) 9.2, 8.6,
5.6, 3.6 Hz, 1H), 3.76 (ddd, J ) 12.2, 5.6, 5.0 Hz, 1H), 7.32-7.37 (m,
3H), 7.50-7.55 (m, 2H); 13C NMR δ -2.46 (CH3), -1.82 (CH3), 25.15
(CH2), 25.81 (CH2), 26.64 (CH2), 30.94 (CH2), 39.69 (CH2), 67.84
(CH2), 77.67 (CH), 127.65 (CH × 2), 128.67 (CH), 133.57 (CH × 2),
139.80 (C); MS m/z (relative intensity) 248 (M+, 0.1), 233 (M+ - Me,
50), 135 (100). Anal. Calcd for C15H24OSi: C, 72.52; H, 9.74. Found:
C, 72.25; H, 9.91.
3H), 1.00-1.10 (m, 1H) including 1.04 (dd, J ) 14.2, 8.6 Hz), 1.25-
1.57 (m, 13H), 1.80-2.05 (m, 2H), 3.63-3.73 (m, 0.14H), 3.82-3.95
(m, 1H), 4.05 (tt, J ) 8.3, 5.9 Hz, 0.86H), 7.32-7.36 (m, 3H), 7.49-
7.56 (m, 2H); 13C NMR for major isomer δ -2.39 (CH3), -2.12 (CH3),
14.09 (CH3), 22.61 (CH2), 23.94 (CH2), 26.29 (CH2), 29.40 (CH2), 31.84
(CH2), 32.62 (CH2), 34.88 (CH2), 36.32 (CH2), 76.10 (CH), 77.99 (CH),
127.69 (CH × 2), 128.82 (CH), 133.55 (CH × 2), 139.26 (C), for minor
isomer δ -2.32 (CH3), -1.99 (CH3), 31.52 (CH2), 31.57 (CH2), 76.91
(CH), 78.76 (CH); MS m/z (relative intensity) 304 (M+, 0.2), 289 (M+
- Me, 8.7), 135 (100). Anal. Calcd for C19H32OSi: C, 74.93; H, 10.59.
Found: C, 74.89; H, 10.55.
(2R*,1′S*)-2-[Deuterio(dimethylphenylsilyl)methyl]tetrahydro-
furan (12): bp 70 °C (0.30 Torr); IR (neat) 2960, 1249, 1112, 1077,
2-Dimethylphenylsilylmethyl-5-isopropyltetrahydrofuran (18c,
trans:cis ) 89:11): bp 100 °C (0.30 Torr); IR (neat) 2920, 1248,
1
832, 700 cm-1; H NMR δ 0.317 (s, 3H), 0.321 (s, 3H), 1.04 (d, J )
1109, 838, 822, 727, 699 cm-1 1H NMR δ 0.31 (s, 3H), 0.32
;
8.6 Hz, 1H), 1.21-1.40 (m, 1H), 1.75-1.94 (m, 3H), 3.59-3.67 (m,
(s, 3H), 0.81-0.86 (m, 3H) including 0.82 (d, J ) 6.6 Hz), 0.92-0.96
(m, 3H) including 0.93 (d, J ) 6.6 Hz), 1.00-1.09 (m, 1H), 1.25-
1.67 (m, 4H), 1.75-1.96 (m, 2H), 3.40 (q, J ) 6.9 Hz, 0.11H), 3.59
(ddd, J ) 8.3, 7.3, 5.6 Hz, 0.89H), 3.82-3.93 (m, 0.11H), 4.00 (tdd,
J ) 7.9, 6.6, 5.0 Hz, 0.89H), 7.32-7.36 (m, 3H), 7.50-7.54 (m, 2H);
13C NMR for major isomer δ -2.39 (CH3), -2.03 (CH3), 18.40 (CH3),
19.42 (CH3), 23.94 (CH2), 30.24 (CH2), 33.52 (CH), 35.42 (CH2), 76.53
(CH), 83.62 (CH), 127.68 (CH × 2), 128.78 (CH), 133.59 (CH × 2),
139.44 (C), for minor isomer δ -2.32 (CH3), 18.61 (CH3), 29.03 (CH2),
33.32 (CH), 33.93 (CH2), 76.80 (CH), 84.27 (CH); MS m/z (relative
intensity) 262 (M+, 0.2), 247 (M+ - Me, 6), 75 (100). Anal. Calcd for
C16H26OSi: C, 73.22; H, 9.98. Found: C, 73.24; H, 9.77.
1H), 3.80-3.92 (m, 2H), 7.33-7.36 (m, 3H), 7.50-7.55 (m, 2H); 13
C
NMR δ -2.39 (CH3), -2.14 (CH3), 23.08 (CHD, t, JC-D ) 18.0 Hz),
25.97 (CH2), 33.79 (CH2), 66.96 (CH2), 77.11 (CH), 127.74 (CH ×
2), 128.89 (CH), 133.55 (CH × 2), 139.17 (C); MS m/z (relative
intensity) 206 (M+ - Me, 26), 43 (100). Anal. Calcd for C13H19DOSi:
C, 70.53; H, 8.65; D, 0.91. Found: C, 70.68; H, 8.72; D, 0.92.
(2R*,1′R*)-2-[Deuterio(dimethylphenylsilyl)methyl]tetrahydro-
1
furan (13): IR (neat) 2935, 1250, 1106, 831 cm-1; H NMR δ 0.317
(s, 3H), 0.321 (s, 3H), 1.22-1.39 (m, 2H), 1.71-1.94 (m, 3H), 3.58-
3.67 (m, 1H), 3.81-3.92 (m, 2H), 7.33-7.37 (m, 3H), 7.50-7.55 (m,
2H); 13C NMR δ -2.53 (CH3), -2.24 (CH3), 22.93 (CHD, t, JC-D
)
18.3 Hz), 25.81 (CH2), 33.69 (CH2), 66.78 (CH2), 76.93 (CH), 127.58
(CH × 2), 128.72 (CH), 133.39 (CH × 2), 138.96 (C); MS m/z (relative
intensity) 206 (M+ - Me, 32), 135 (100). Anal. Calcd for C13H19-
DOSi: C, 70.53; H, 8.65; D, 0.91. Found: C, 70.46; H, 8.90; D, 0.94.
(2R*,1′S*)-2-[Deuterio(dimethylphenylsilyl)methyl]tetrahydro-
pyran (15): IR (neat) 2930, 1246, 1109, 1083, 838, 698 cm-1; 1H NMR
δ 0.30 (s, 3H), 0.31 (s, 3H), 0.97 (dt, J ) 6.3, 2.0 Hz, 1H), 1.17-1.60
(m, 5H), 1.70-1.77 (m, 1H), 3.30-3.39 (m, 2H), 3.89-3.96 (m, 1H),
7.32-7.37 (m, 3H), 7.49-7.55 (m, 2H); 13C NMR δ -2.37 (CH3),
-1.80 (CH3), 23.78 (CH2), 24.21 (CHD, t, JC-D ) 18.3 Hz),
25.79 (CH2), 34.97 (CH2), 68.32 (CH2), 75.85 (CH), 127.64 (CH ×
2), 128.72 (CH), 133.57 (CH × 2), 139.59 (C); MS m/z (relative
intensity) 235 (M+, 0.1), 220 (M+ - Me, 43), 135 (100). Anal. Calcd
for C14H21DOSi: C, 71.43; H, 8.99; D, 0.86. Found: C, 71.32; H, 8.99;
D, 0.86.
2-Dimethylphenylsilylmethyl-4-phenyltetrahydrofuran (20a,
trans:cis ) 11:89): bp 150 °C (0.30 Torr); IR (neat) 1250, 1110, 836,
698 cm-1; 1H NMR δ 0.34 (s, 6H), 1.09-1.24 (m, 1H) including 1.20
(dd, J ) 14.2, 8.7 Hz), 1.35-1.59 (m, 1.89H) including 1.46 (dd, J )
14.2, 5.8 Hz), 1.83-2.10 (m, 0.22H), 2.35 (ddd, J ) 12.2, 7.9, 5.3 Hz,
0.89H), 3.33-3.46 (m, 1H), 3.60 (dd, J ) 8.5, 8.2, 0.11H), 3.79 (dd,
J ) 8.3, 7.9 Hz, 0.89H), 4.03-4.14 (m, 1.78H), 4.18-4.28 (m, 0.22H),
7.17-7.38 (m, 8H), 7.51-7.55 (m, 2H); 13C NMR for major isomer δ
-2.28 (CH3), -2.17 (CH3), 23.54 (CH2), 43.76 (CH2), 46.00 (CH),
73.73 (CH2), 78.15 (CH), 126.29 (CH), 127.08 (CH × 2), 127.73 (CH
× 2), 128.43 (CH × 2), 128.90 (CH), 133.48 (CH × 2), 138.81 (C),
143.11 (C), for minor isomer δ 24.14 (CH2), 42.37 (CH2), 44.85 (CH),
74.25 (CH2), 77.47 (CH), 127.19 (CH × 2), 138.92 (C), 142.93 (C);
MS m/z (relative intensity) 296 (M+, 0.1), 281 (M+ - Me, 8.0), 135
(100). Anal. Calcd for C19H24OSi: C, 76.97; H, 8.16. Found: C, 77.02;
H, 8.17.
(2R*,1′R*)-2-[Deuterio(dimethylphenylsilyl)methyl]tetrahydro-
1
pyran (16): IR (neat) 2930, 1246, 1110, 1084, 837, 698 cm-1; H
2-Dimethylphenylsilylmethyl-4-hexyltetrahydrofuran
(20b,
NMR δ 0.30 (s, 3H), 0.32 (s, 3H), 1.11 (dt, J ) 7.6, 2.0 Hz, 1 H),
1.18-1.56 (m, 5H), 1.70-1.79 (m, 1H), 3.30-3.40 (m, 2H), 3.90-
3.96 (m, 1H), 7.32-7.37 (m, 3H), 7.49-7.55 (m, 2H); 13C NMR δ
-2.37 (CH3), -1.80 (CH3), 23.76 (CH2), 24.20 (CHD, t, JC-D ) 17.7
Hz), 25.79 (CH2), 34.99 (CH2), 68.30 (CH2), 75.83 (CH), 127.62 (CH
× 2), 128.70 (CH), 133.55 (CH × 2), 139.57 (C); MS m/z (relative
intensity) 235 (M+, 0.1), 220 (M+ - Me, 45), 135 (99), 43 (100). Anal.
Calcd for C14H21DOSi: C, 71.43; H, 8.99; D, 0.86. Found: C, 71.23;
H, 9.00; D, 0.86.
trans:cis ) 15:85): bp 160 °C (0.30 Torr); IR (neat) 2920, 1248, 1113,
1
835, 727, 698 cm-1; H NMR δ 0.31 (s, 6H), 0.85-1.56 (m, 16H),
1.97-2.24 (m, 2H), 3.20 (dd, J ) 8.3, 7.9 Hz, 0.15H), 3.41 (dd, J )
7.9, 7.6 Hz, 0.85H), 3.79 (t, J ) 7.9 Hz, 0.85H), 3.86-4.04 (m, 1.15H),
7.32-7.37 (m, 3H), 7.48-7.54 (m, 2H); 13C NMR for major isomer δ
-2.28 (CH3), -2.17 (CH3), 14.07 (CH3), 22.59 (CH2), 23.79 (CH2),
28.48 (CH2), 29.38 (CH2), 31.75 (CH2), 34.11 (CH2), 40.47 (CH), 41.62
(CH2), 72.47 (CH2), 77.65 (CH), 127.73 (CH × 2), 128.88 (CH), 133.53
(CH × 2), 139.08 (C), for minor isomer δ 23.97 (CH2), 28.36 (CH2),
33.75 (CH2), 39.18 (CH), 40.38 (CH2), 72.99 (CH2), 77.20 (CH); MS
2-Dimethylphenylsilylmethyl-5-phenyltetrahydrofuran (18a,
trans:cis ) 85:15): bp 180 °C (0.50 Torr); IR (neat) 1248, 1112, 836,

11356 J. Am. Chem. Soc., Vol. 122, No. 46, 2000
Miura et al.
m/z (relative intensity) 289 (M+ - Me, 11), 135 (100). Anal. Calcd
for C19H32OSi: C, 74.93; H, 10.59. Found: C, 75.06; H, 10.59.
Purification by column chromatography (SiO2, hexane-AcOEt 1:1)
gave 23a (30.1 mg, 59%, trans:cis ) 90:10).
Method C. TBAF (1.0 M in THF, 1.5 mL, 1.5 mmol), MeOH (1.5
mL), KHCO3 (83 mg, 0.83 mmol), and H2O2 (30% in water, 0.45 mL,
4.0 mmol) were added to 18k (126 mg, 0.406 mmol, trans:cis ) 88:
12). The mixture was stirred for 11 h at 40 °C. The same workup and
purification as described for method B gave 23a (67 mg, 93%, trans:
cis ) 88:12).
2-Dimethylphenylsilylmethyl-4-isopropyltetrahydrofuran (20c,
trans:cis ) 10:90): bp 90 °C (0.30 Torr); IR (neat) 2955, 1248, 1113,
836, 728, 698 cm-1 1H NMR δ 0.31 (s, 6H), 0.81-0.87 (m, 6H)
;
including 0.83 (d, J ) 5.9 Hz) and 0.85 (d, J ) 5.9 Hz), 0.95-1.12
(m, 2H) including 1.07 (dd, J ) 14.2, 8.9 Hz), 1.24-1.65 (m, 2.1H)
including 1.35 (dd, J ) 14.2, 5.4 Hz), 1.82-2.01 (m, 1.9H), 3.25 (t, J
) 8.9 Hz, 0.1H), 3.48 (dd, J ) 8.2, 7.6 Hz, 0.9H), 3.81 (t, J ) 8.2 Hz,
0.9H), 3.87-4.01 (m, 1.1H), 7.32-7.37 (m, 3H), 7.48-7.54 (m, 2H);
13C NMR for major isomer δ -2.30 (CH3), -2.16 (CH3), 21.33 (CH3),
21.46 (CH3), 23.67 (CH2), 32.27 (CH), 40.05 (CH2), 48.09 (CH), 71.13
(CH2), 77.86 (CH), 127.70 (CH × 2), 128.85 (CH), 133.52 (CH × 2),
139.11 (C), for minor isomer δ 21.21 (CH3), 24.19 (CH2), 31.72 (CH),
38.56 (CH2), 46.64 (CH), 71.65 (CH2), 77.00 (CH); MS m/z (relative
intensity) 262 (M+, 0.3) 247 (M+ - Me, 11), 75 (100). Anal. Calcd
for C16H26OSi: C, 73.22; H, 9.98. Found: C, 73.22; H, 10.03.
2-Hydroxymethyl-5-hexyltetrahydrofuran (23b, trans:cis
)
;
87:13): bp 110 °C (0.31 Torr); IR (neat) 3430 (br), 2930, 1044 cm-1
1H NMR δ 0.88 (t, J ) 6.8 Hz, 3H), 1.28-1.73 (m, 12H), 1.83-2.08
(m, 3H), 3.43-3.53 (m, 1H), 3.59-3.74 (m, 1H) including 3.63 (ddd,
J ) 11.6, 6.9, 3.3 Hz), 3.82-4.15 (m, 2H); 13C NMR for major isomer
δ 14.04 (CH3), 22.57 (CH2), 26.13 (CH2), 27.53 (CH2), 29.36 (CH2),
31.79 (CH2), 32.02 (CH2), 35.73 (CH2), 65.03 (CH2), 78.83 (CH), 79.50
(CH), for minor isomer δ 27.03 (CH2), 31.38 (CH2), 35.90 (CH2), 65.28
(CH2), 79.16 (CH), 80.20 (CH); MS m/z (relative intensity) 155 (M+
- CH2OH, 45), 41 (100). Anal. Calcd for C11H22O2: C, 70.92; H, 11.90.
Found: C, 70.59; H, 11.90.
trans-2-Dimethylphenylsilylmethyl-3-phenyltetrahydrofuran
(trans-22a): bp 180 °C (0.50 Torr); IR (neat) 1247, 1112, 836, 819,
2-Hydroxymethyl-5-isopropyltetrahydrofuran (23c, trans:cis )
93:7): bp 160 °C (38 Torr); IR (neat) 3425 (br), 2965, 1045 cm-1; 1H
NMR δ 0.85-0.89 (m, 3H) including 0.87 (d, J ) 6.9 Hz), 0.95-0.99
(m, 3H) including 0.96 (d, J ) 6.6 Hz), 1.52-1.75 (m, 3H), 1.87-
2.02 (m, 3H), 3.44-3.67 (m, 3H), 3.98-4.12 (m, 1H); 13C NMR for
major isomer δ 18.09 (CH3), 19.19 (CH3), 27.68 (CH2), 29.20 (CH2),
32.89 (CH), 64.82 (CH2), 79.32 (CH), 84.76 (CH), for minor isomer δ
18.27 (CH3), 27.13 (CH2), 28.46 (CH2), 65.16 (CH2), 79.18 (CH), 85.42
(CH); MS m/z (relative intensity) 113 (M+ - CH2OH, 23), 57 (100).
Anal. Calcd for C8H16O2: C, 66.63; H, 11.18. Found: C, 66.70; H,
11.03.
1
698 cm-1; H NMR δ 0.27 (s, 3H), 0.29 (s, 3H), 1.06 (dd, J ) 14.8,
8.6 Hz, 1H), 1.10 (dd, J ) 14.8, 5.0 Hz, 1H), 2.02 (dtd, J ) 12.5, 8.6,
7.3 Hz, 1H), 2.30-2.42 (m, 1H), 2.81 (dt, J ) 8.6, 8.3 Hz, 1H), 3.86-
4.05 (m, 3H), 7.13-7.33 (m, 8H), 7.43-7.49 (m, 2H); 13C NMR δ
-2.57 (CH3), -1.74 (CH3), 21.30 (CH2), 35.33 (CH2), 54.39 (CH),
66.99 (CH2), 83.98 (CH), 126.46 (CH), 127.65 (CH × 4), 128.53 (CH
× 2), 128.71 (CH), 133.62 (CH × 2), 139.62 (C), 142.14 (C); MS m/z
(relative intensity) 281 (M+ - Me, 2.1), 118 (100). Anal. Calcd for
C19H24OSi: C, 76.97; H, 8.16. Found: C, 77.17; H, 8.31.
trans-2-Dimethylphenylsilylmethyl-3-pentyltetrahydrofuran
(trans-22b): bp 135 °C (0.30 Torr); IR (neat) 2920, 1246, 1112, 837,
820, 698 cm-1; 1H NMR δ 0.33 (s, 3H), 0.34 (s, 3H), 0.87 (t, J ) 6.8
Hz, 3H), 0.98-1.65 (m, 12H) including 1.03 (dd, J ) 14.5, 8.6 Hz)
and 1.14 (dd, J ) 14.5, 4.6 Hz), 2.03 (dtd, J ) 11.9, 7.6, 5.3 Hz, 1H),
3.50 (ddd, J ) 8.6, 6.9, 4.6 Hz, 1H), 3.70 (td, J ) 8.3, 5.6 Hz, 1H),
3.81 (ddd, J ) 8.3, 7.5, 6.6 Hz, 1H), 7.31-7.36 (m, 3H), 7.51-7.57
(m, 2H); 13C NMR δ -2.48 (CH3), -1.70 (CH3), 14.05 (CH3), 22.21
(CH2), 22.57 (CH2), 28.09 (CH2), 32.01 (CH2), 32.29 (CH2), 32.74
(CH2), 47.78 (CH), 66.33 (CH2), 82.28 (CH), 127.66 (CH × 2),
128.70 (CH), 133.59 (CH × 2), 139.82 (C); MS m/z (relative intensity)
290 (M+, 0.2), 275 (M+ - Me, 6.7), 135 (100). Anal. Calcd for
C18H30OSi: C, 74.42; H, 10.41. Found: C, 74.50; H, 10.53.
2-Hydroxymethyl-4-phenyltetrahydrofuran (24, trans:cis
)
15:85): bp 120 °C (0.55 Torr); IR (neat) 3420 (br), 2925, 1602, 1495,
1454 cm-1; 1H NMR δ 1.82-1.95 (m, 0.85H), 2.05-2.24 (m, 1.30H),
2.35 (ddd, J ) 12.5, 7.6, 6.3 Hz, 0.85H), 3.41-3.83 (m, 4H), 4.18-
4.34 (m, 2H), 7.19-7.35 (m, 5H); 13C NMR for major isomer δ 35.73
(CH2), 45.49 (CH), 64.76 (CH2), 74.34 (CH2), 80.46 (CH), 126.69 (CH),
127.20 (CH × 2), 128.58 (CH × 2), 141.22 (C), for minor isomer δ
35.66 (CH2), 44.96 (CH), 65.16 (CH2), 74.77 (CH2), 79.50 (CH), 126.60
(CH), 141.96 (C); MS m/z (relative intensity) 178 (M+, 3.1), 41 (100).
Anal. Calcd for C11H14O2: C, 74.13; H, 7.92. Found: C, 74.02; H,
7.88.
trans-2-Hydroxymethyl-3-phenyltetrahydrofuran (trans-25a): bp
Oxidative Cleavage of Si-C Bond (Typical Procedure). Method
A.21 H2O2 (30% in water, 2.3 mL, 20 mmol) was added to a mixture
of 18g (352 mg, 1.60 mmol), KHCO3 (160 mg, 1.60 mmol), MeOH
(3.9 mL), and THF (3.9 mL), and then the mixture was stirred for 2 h
at 60 °C. The reaction mixture was poured into water (50 mL) and
extracted with Et2O (2 × 30 mL). The combined organic layer was
washed with 10% aqueous NaHSO3 (30 mL) and saturated aqueous
NaHCO3 (30 mL), dried, and evaporated. Purification by column
chromatography (SiO2, hexane-AcOEt 1:1) gave 2-hydroxymethyl-
5-phenyltetrahydrofuran (23a, 276 mg, 97%, trans:cis ) 96:4).
145 °C (0.59 Torr); IR (neat) 3415 (br), 3025, 1050, 756, 701 cm-1
;
1H NMR δ 1.87 (br s, 1H), 2.18 (ddt, J ) 12.5, 9.6, 8.3 Hz, 1H), 2.39
(dddd, J ) 12.5, 8.3, 6.9, 4.3 Hz, 1H), 3.20 (dt, J ) 9.6, 8.3 Hz, 1H),
3.54 (dd, J ) 11.6, 5.0 Hz, 1H), 3.75 (dd, J ) 11.6, 3.0 Hz, 1H), 3.94
(ddd, J ) 8.3, 5.0, 3.0 Hz, 1H), 4.01 (td, J ) 8.3, 6.9 Hz, 1H), 4.12
(td, J ) 8.3, 4.3 Hz, 1H), 7.20-7.36 (5H); 13C NMR δ 35.40 (CH2),
46.08 (CH), 62.77 (CH2), 68.25 (CH2), 86.29 (CH), 126.77 (CH), 127.60
(CH × 2), 128.70 (CH × 2), 141.15 (C); MS m/z (relative intensity)
178 (M+, 2.3), 147 (100). Anal. Calcd for C11H14O2: C, 74.13; H, 7.92.
Found: C, 73.74; H, 8.05.
23a: bp 145 °C (0.41 Torr); IR (neat) 3420 (br), 1044, 700 cm-1
;
trans-2-Hydroxymethyl-3-pentyltetrahydrofuran (trans-25b): IR
1H NMR δ 1.61 (br s, 1H), 1.76-1.96 (m, 2H), 2.03-2.16 (m, 2H),
2.28-2.43 (m, 1H), 3.55-3.85 (m, 2H) including 3.74 (ddd, J ) 11.5,
6.9, 3.3 Hz), 4.17-4.25 (m, 0.04H), 4.33-4.42 (m, 0.96H), 4.93 (dd,
J ) 7.8, 6.4 Hz, 0.04H), 5.01 (dd, J ) 7.9, 5.9 Hz, 0.96H), 7.23-7.36
(m, 5H); 13C NMR for major isomer δ 27.83 (CH2), 35.35 (CH2), 65.09
(CH2), 80.13 (CH), 80.87 (CH), 125.56 (CH × 2), 127.29 (CH), 128.33
(CH × 2), 142.86 (C); MS m/z (relative intensity) 178 (M+, 7.3), 91
(100). Anal. Calcd for C11H14O2: C, 74.13; H, 7.92%. Found: C, 74.22;
H, 8.04%.
1
(neat) 3400 (br), 2905, 1449, 1042 cm-1; H NMR δ 0.88 (t, J ) 6.8
Hz, 3H), 1.25-1.50 (m, 8H), 1.58 (dq, J ) 11.9, 7.9 Hz, 1H), 1.66-
2.00 (m, 2H), 2.09 (dddd, J ) 11.9, 7.6, 6.6, 4.6 Hz, 1H), 3.51 (dd, J
) 11.2, 5.9 Hz, 1H), 3.54-3.61 (m, 1H), 3.71 (dd, J ) 11.2, 2.6 Hz,
1H), 3.80 (td, J ) 8.3, 6.6 Hz, 1H), 3.88 (td, J ) 8.3, 4.6 Hz, 1H); 13
C
NMR δ 13.95 (CH3), 22.48 (CH2), 27.93 (CH2), 31.86 (CH2), 32.98
(CH2), 33.01 (CH2), 40.15 (CH), 63.99 (CH2), 67.46 (CH2), 85.05 (CH);
MS m/z (relative intensity) 141 (M+ - CH2OH, 65), 55 (100). HRMS
calcd for C9H17O (M+ - CH2OH): 141.1279. Found: 141.1277.
Conversion of Alcohols to Iodides (Typical Procedure). A solution
of 23a (178 mg, 1.00 mmol, trans:cis ) 96:4) in CH2Cl2 (2 mL) was
added to a mixture of TsCl (286 mg, 1.50 mmol), Et3N (0.42 mL, 3.0
mmol), and CH2Cl2 (1 mL) at room temperature. After 15 h the reaction
mixture was poured into saturated aqueous NaHCO3 (20 mL). The
extract with Et2O (3 × 20 mL) was dried and evaporated. The residual
oil was treated with NaI (900 mg, 6.00 mmol) in acetone (3 mL) at 60
°C for 23 h. The resultant mixture was subjected to the same workup
as described for the above tosylation. Purification by column chroma-
Method B.22 t-BuOK (40 mg, 0.32 mmol) was added to a solution
of 18a (85.0 mg, 0.287 mmol, trans:cis ) 92:8) in DMSO (0.7 mL).
The mixture was stirred for 6 h at room temperature and then diluted
with phosphate buffer solution (pH 7, 10 mL). The extract with ether
(2 × 10 mL) was evaporated. MeOH (1 mL), KHCO3 (63 mg, 0.63
mmol), TBAF (1M in THF, 1.1 mL, 1.1 mmol), and H2O2 (30% in
water, 0.40 mL, 3.5 mmol) were added to the residue. The mixture
was stirred for 14 h at 40 °C and then poured into 10% aqueous Na2S2O3
(20 mL). The extract with Et2O (2 × 10 mL) was dried and evaporated.

Cyclization of Vinylsilanes Bearing a Hydroxy Group
J. Am. Chem. Soc., Vol. 122, No. 46, 2000 11357
tography (SiO2, hexane-AcOEt 20:1) gave 2-iodomethyl-5-phenyl-
tetrahydrofuran (26a, 258 mg, 89%, trans:cis ) 96:4).
NMR δ 0.90 (t, J ) 6.5 Hz, 3H), 1.14-1.56 (m, 8H), 1.58-1.79 (m,
1H), 1.88-2.29 (m, 2H), 3.09-3.22 (m, 0.86H), 3.22 (dd, J ) 10.4,
5.6 Hz, 0.57H), 3.36 (dd, J ) 10.4, 4.8 Hz, 0.57H), 3.45-3.52 (m,
0.57H), 3.76-4.02 (m, 2H), 4.14 (ddd, J ) 8.0, 6.2, 5.6 Hz, 0.43H);
13C NMR (see trans-30b for trans isomer) for cis isomer δ 6.20 (CH2),
14.04 (CH3), 22.55 (CH2), 27.94 (CH2), 28.02 (CH2), 28.89 (CH2), 31.86
(CH2), 41.94 (CH), 66.99 (CH2), 81.28 (CH); MS m/z (relative intensity)
for cis isomer 282 (M+, 0.2), 55 (100). Anal. Calcd for C10H19IO: C,
42.57; H, 6.79. Found: C, 42.52; H, 7.00.
Iodocyclization of 2,6-Dichlorobenzyl Ethers (Typical Proce-
dure).25 A solution of 5-(2,6-dichlorobenzyloxy)-1-undecene (28b, 329
mg, 1.00 mmol) in CH3CN (5 mL) was treated with I2 (380 mg, 1.50
mmol) at 0 °C for 1 h. The reaction mixture was subjected to the same
workup as iodocyclization of alkenols. Purification by column chro-
matography (SiO2, hexane-AcOEt, 20:1) gave 26b (247 mg, 83%,
trans:cis ) <2:98).
cis-26b: bp 115 °C (0.53 Torr); IR (neat) 2910, 1451, 1085, 1040
cm-1; 1H NMR δ 0.88 (t, J ) 6.8 Hz, 3H), 1.19-1.79 (m, 12H), 1.91-
2.13 (m, 2H), 3.16 (dd, J ) 9.8, 6.8 Hz, 1H), 3.26 (dd, J ) 9.8, 4.5
Hz, 1H), 3.86-4.02 (m, 2H); 13C NMR δ 10.93 (CH2), 14.05 (CH3),
22.57 (CH2), 26.06 (CH2), 29.33 (CH2), 30.95 (CH2), 31.52 (CH2), 31.77
(CH2), 36.08 (CH2), 78.26 (CH), 80.95 (CH); MS m/z (relative intensity)
211 (M+ - C6H13, 0.2), 55 (100). Anal. Calcd for C11H21IO: C, 44.61;
H, 7.15. Found: C, 44.91; H, 7.38.
26a (trans:cis ) 96:4): bp 140 °C (0.31 Torr); IR (neat) 1047, 697
cm-1; 1H NMR δ 1.77-2.00 (m, 2H), 2.25-2.47 (m, 2H), 3.25-3.41
(m, 2H) including 3.29 (dd, J ) 9.9, 7.3 Hz) and 3.37 (dd, J ) 9.9,
4.6 Hz), 4.12-4.21 (m, 0.04H), 4.28-4.37 (m, 0.96H), 4.96 (dd, J )
7.6, 6.6 Hz, 0.04H), 5.12 (dd, J ) 7.9, 6.3 Hz, 0.96H), 7.21-7.37 (m,
5H); 13C NMR for major isomer δ 10.95 (CH2), 32.78 (CH2), 35.35
(CH2), 78.85 (CH), 81.46 (CH), 125.43 (CH × 2), 127.23 (CH), 128.24
(CH × 2), 142.64 (C), for minor isomer δ 10.59 (CH2), 31.77 (CH2),
34.25 (CH2), 78.55 (CH), 82.09 (CH), 125.74 (CH); MS m/z (relative
intensity) 288 (M+, 43), 147 (M+ - CH2I, 78), 55 (100). Anal. Calcd
for C11H13IO: C, 45.85; H, 4.55. Found: C, 45.59; H, 4.40.
2-Iodomethyl-5-hexyltetrahydrofuran (26b, trans:cis ) 87:13):
bp 100 °C (0.20 Torr); IR (neat) 2935, 1045 cm-1; 1H NMR δ 0.88 (t,
J ) 6.8 Hz, 3H), 1.28-1.75 (m, 12H), 1.92-2.24 (m, 2H), 3.13-3.31
(m, 2H) including 3.17 (dd, J ) 9.6, 7.6 Hz) and 3.27 (dd, J ) 9.6,
4.6 Hz), 3.87-4.02 (m, 0.26H), 3.99-4.12 (m, 1.74H); 13C NMR for
major isomer δ 11.23 (CH2), 14.06 (CH3), 22.57 (CH2), 25.97 (CH2),
29.34 (CH2), 31.77 (CH2), 32.17 (CH2), 32.56 (CH2), 35.78 (CH2), 77.90
(CH), 80.31 (CH), for minor isomer δ 10.93 (CH2), 26.05 (CH2), 30.96
(CH2), 31.52 (CH2), 36.09 (CH2), 78.26 (CH), 80.96 (CH); MS m/z
(relative intensity) 296 (M+, 0.1), 55 (100). Anal. Calcd for C11H21IO:
C, 44.61; H, 7.15. Found: C, 44.80; H, 7.33.
2-Iodomethyl-5-isopropyltetrahydrofuran (26c, trans:cis
)
Deoxygenation of Alcohol 24. BuLi (1.69 M in hexane, 0.74 mL,
1.25 mmol) was added dropwise to a solution of 24 (cis:trans ) 85:
15, 203 mg, 1.14 mmol) in THF (4 mL) at -78 °C. After 10 min, a
THF (2 mL) solution of TsCl (238 mg, 1.25 mmol) was added to the
mixture. After additional 10 min, the mixture was warmed to room
temperature and stirred for 30 min. The resulting mixture was subjected
to a usual aqueous workup. The crude product obtained (a white solid)
was dissolved in THF (2 mL) and added to a suspension of LiAlH4
(50 mg, 1.3 mmol) in THF (3 mL) at 0 °C. After being stirred at room
temperature for 12 h, the resulting mixture was quenched with 20%
aqueous potassium sodium tartrate (15 mL). The extract with t-BuOMe
(2 × 20 mL) was dried and evaporated. Purification of the residual oil
by column chromatography (SiO2, hexane-AcOEt 10:1) gave 2-methyl-
4-phenyltetrahydrofuran (29, 124 mg, 67%, cis:trans ) 85:15).
93:7) (CAS Registry No. [78631-56-8] for trans isomer, [78631-52-
4] for cis isomer; registry numbers provided by the author):25 1H NMR
δ 0.84-0.98 (m, 6H) including 0.85 (d, J ) 6.6 Hz) and 0.95 (d, J )
6.6 Hz), 1.61-1.74 (m, 3H), 1.95-2.24 (m, 2H), 3.12-3.32 (m, 2H)
including 3.16 (dd, J ) 9.9, 7.6 Hz) and 3.28 (dd, J ) 9.6, 4.6 Hz),
3.59-3.68 (m, 0.07H), 3.72-3.80 (m, 0.93H), 3.94-4.10 (m, 1H).
trans-2-Iodomethyl-3-phenyltetrahydrofuran (trans-30a): bp 130
°C (0.60 Torr); IR (neat) 2873, 1601, 1493, 1047, 756 cm-1; 1H NMR
δ 2.26 (ddt, J ) 12.5, 9.5, 8.3 Hz, 1H), 2.40-2.53 (m, 1H), 3.07-
3.17 (m, 1H), 3.21 (dd, J ) 10.4, 5.4 Hz, 1H), 3.41 (dd, J ) 10.4, 3.9
Hz, 1H), 3.73 (ddd, J ) 9.2, 5.3, 3.9 Hz, 1H), 4.04-4.18 (m, 2H),
7.22-7.38 (m, 5H); 13C NMR δ 9.62 (CH2), 35.24 (CH2), 50.98 (CH),
68.11 (CH2), 84.28 (CH), 126.95 (CH), 127.44 (CH × 2), 128.73 (CH
× 2), 140.43 (C); MS m/z (relative intensity) 288 (M+, 6.0), 161 (100).
Anal. Calcd for C11H13IO: C, 45.86; H, 4.55. Found: C, 45.89; H, 4.55.
trans-2-Iodomethyl-3-pentyltetrahydrofuran (trans-30b): IR (neat)
1
29: bp 130 °C (26 Torr); IR (neat) 2968, 756, 700 cm-1; H NMR
δ 1.30 (d, J ) 6.1 Hz, 0.45H), 1.36 (d, J ) 6.1 Hz, 2.55H), 1.62 (dt,
J ) 12.2, 10.0 Hz, 0.85H), 1.97 (ddd, J ) 12.5, 9.1, 6.4 Hz, 0.15H),
2.15 (dt, J ) 12.5, 7.2 Hz, 0.15H), 2.45 (ddd, J ) 12.2, 7.6, 5.4 Hz,
0.85H), 3.40-3.53 (m, 1H), 3.70 (t, J ) 8.3 Hz, 0.15H), 3.83 (dd, J )
8.2, 7.9 Hz, 0.85H), 4.08-4.34 (m, 2H), 7.17-7.34 (m, 5H); 13C NMR
for cis isomer δ 20.86 (CH3), 42.86 (CH2), 45.94 (CH), 74.34 (CH2),
76.35 (CH), 126.44 (CH), 127.17 (CH × 2), 128.53 (CH × 2), 142.88
(C), for trans isomer δ 21.63 (CH3), 41.37 (CH2), 44.75 (CH), 74.74
(CH2), 75.48 (CH), the signals of the phenyl group overlapped those
of cis isomer; MS m/z (relative intensity) for cis isomer 162 (M+, 21),
117 (100), for trans isomer 162 (M+, 17), 117 (100).
1
2925, 1460, 1049 cm-1; H NMR δ 0.87-0.93 (m, 3H), 1.21-1.56
(m, 8H), 1.64 (dq, J ) 11.9, 7.7 Hz, 1H), 1.86-2.00 (m, 1H),
2.09-2.22 (m, 1H), 3.22 (dd, J ) 10.4, 5.6 Hz, 1H), 3.36 (dd,
J ) 10.4, 4.8 Hz, 1H), 3.45-3.52 (m, 1H), 3.82-3.96 (m, 2H);
13C NMR δ 10.51 (CH2), 13.98 (CH3), 22.50 (CH2), 27.78 (CH2),
31.83 (CH2), 32.89 (CH2), 33.10 (CH2), 44.94 (CH), 67.64 (CH2), 83.31
(CH); MS m/z (relative intensity) 282 (M+, 0.6), 55 (100). HRMS
calcd for C10H19IO: 282.0481. Found: 282.0470.
Iodocyclization of Alkenols (Typical Procedure).25 A mixture of
1-phenyl-4-penten-1-ol (27a, 324 mg, 2.00 mmol) and NaHCO3 (252
mg, 3.00 mmol) in CH3CN (5 mL) was treated with I2 (761 mg, 3.00
mmol) at 0 °C for 4.5 h. The reaction mixture was poured into 10%
aqueous Na2S2O3 (20 mL). The extract with Et2O (3 × 15 mL) was
dried and evaporated. Purification by column chromatography (SiO2,
hexane-AcOEt, 20:1) gave 26a (351 mg, 61%, trans:cis ) 74:26).
2-Iodomethyl-3-phenyltetrahydrofuran (30a, trans:cis ) 64:36):
Acknowledgment. This work was partly supported by
Grants-in-Aid for Scientific Research, Grants-in-Aid for
Scientific Research on Priority Areas (Dynamic Control of
Stereochemistry) from the Ministry of Education, Science,
Sports and Culture, Japan, Hitachi Chemical Industries,
Inc., and Pfizer Pharmaceuticals, Inc. We thank Dow Corning
Toray Silicone Co. Ltd. and Shin-Etsu Chemical Co. Ltd. for a
gift of organosilicon compounds.
bp 130 °C (0.60 Torr); IR (neat) 2970, 1601, 1493, 1047, 756 cm-1
;
1H NMR δ 2.16-2.33 (m, 1H), 2.40-2.55 (m, 1H), 2.70 (dd, J )
10.1, 5.6 Hz, 0.36H), 2.89 (dd, J ) 10.1, 8.0 Hz, 0.36H), 3.07-3.17
(m, 0.64H), 3.21 (dd, J ) 10.4, 5.4 Hz, 0.64H), 3.41 (dd, J ) 10.4,
3.9 Hz, 0.64H), 3.52 (ddd, J ) 8.3, 5.6, 5.6 Hz, 0.36H), 3.73 (ddd, J
) 9.2, 5.3, 3.9 Hz, 0.64H), 3.98 (ddd, J ) 8.6, 8.6, 7.1 Hz, 0.36H),
Supporting Information Available: Experimental proce-
dures for the syntheses of vinylsilanes 1, 6, 8, 11, 14, 17, 19,
and 21, alkenols 10, 27, and 31, authentic samples of 12, 13,
15, 16, and cis-29, and dichlorobenzyl ethers 28; spectral data
for all substrates, their synthetic intermediates, and cyclized
products 18d-k, 20d-j, and 22c-g; and yield at each reaction
time in the cyclization of (Z)-1a and (E)-1a (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
4.04-4.18 (m, 1.28H), 4.21-4.33 (m, 0.72H), 7.19-7.38 (m, 5H); 13
C
NMR (see trans-30a for trans isomer) for cis isomer δ 5.39 (CH2),
33.07 (CH2), 47.57 (CH), 67.26 (CH2), 82.50 (CH), 126.70 (CH), 128.23
(CH × 2), 128.30 (CH × 2), 139.82 (C); MS m/z (relative intensity)
for cis isomer 288 (M+, 6.1), 117 (100). Anal. Calcd for C11H13IO: C,
45.86; H, 4.55. Found: C, 45.97; H, 4.66.
2-Iodomethyl-3-pentyltetrahydrofuran (30b, trans:cis ) 57:43):
bp 115 °C (0.70 Torr); IR (neat) 2925, 1458, 1178, 1049 cm-1; H
JA002496Q
1