1,2-Silyl-migrative cyclization of vinylsilanes bearing a hydroxy group: Stereoselective synthesis of multisubstituted tetrahydropyrans and tetrahydrofurans

Article abstract of DOI:10.1021/jo026006j

Acid-catalyzed intramolecular addition of a hydroxy group to α-alkylated vinylsilanes has been studied. Treatment of (Z)-5-alkyl-5-silyl-4-penten-1-ols 1 (R = alkyl) with 5 mol % TiCl₄ in CHCl₃ gave trans-2-alkyl-3-silyltetrahydropyrans 2 exclusively (trans/cis = > 99/1 to 97/3). The cyclization efficiency and rate strongly depended on the geometry of the C-C double bond and the silyl group. The use of (E)-vinylsilanes resulted in lower yields with poor cis-selectivity. In the cyclization of (Z)-1 (R = Bu), the silyl group used, the reaction time, and the yield of 2 were as follows: SiMe₂Ph, 9.5 h, 75%; SiMe₃, 7.5 h, 66%; SiMePh₂, 24 h, 58%; SiMe₂-t-Bu, 0.75 h, 85%; SiMe₂Bn, 1.5 h, 78%. This 1,2-silyl-migrative cyclization could be applied to stereoselective synthesis of trisubstituted tetrahydropyrans. The acid-catalyzed reaction of 1-, 2-, or 3-substituted (Z)-5-silyl-4-nonen-1-ols 8 gave r-2,t-3,c-6-, r-2,t-3,t-5-, or r-2,t-3,c-4-trisubstituted tetrahydropyrans with high diastereo-selectivity, respectively. (Z)-4-Alkyl-4-silyl-3-buten-1-ols 5 as well as 1 underwent the 1,2-silylmigrative cyclization to give 2-alkyl-3-silyltetrahydrofurans 6 with high trans-selectivity. This silicon-directed cyclization was also available for the stereoselective synthesis of tri- and tetrasubstituted tetrahydrofurans.

Full text of DOI:10.1021/jo026006j

1,2-Silyl-Migr a tive Cycliza tion of Vin ylsila n es Bea r in g a Hyd r oxy
Gr ou p : Ster eoselective Syn th esis of Mu ltisu bstitu ted
Tetr a h yd r op yr a n s a n d Tetr a h yd r ofu r a n s1
Katsukiyo Miura, Takeshi Hondo, Shigeo Okajima, Takahiro Nakagawa,
Tatsuyuki Takahashi, and Akira Hosomi*
Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba,
Tsukuba, Ibaraki 305-8571, J apan
hosomi@chem.tsukuba.ac.jp
Received J une 3, 2002
Acid-catalyzed intramolecular addition of a hydroxy group to R-alkylated vinylsilanes has been
studied. Treatment of (Z)-5-alkyl-5-silyl-4-penten-1-ols 1 (R ) alkyl) with 5 mol % TiCl4 in CHCl3
gave trans-2-alkyl-3-silyltetrahydropyrans 2 exclusively (trans/ cis ) >99/1 to 97/3). The cyclization
efficiency and rate strongly depended on the geometry of the C-C double bond and the silyl group.
The use of (E)-vinylsilanes resulted in lower yields with poor cis-selectivity. In the cyclization of
(Z)-1 (R ) Bu), the silyl group used, the reaction time, and the yield of 2 were as follows: SiMe2Ph,
9.5 h, 75%; SiMe3, 7.5 h, 66%; SiMePh2, 24 h, 58%; SiMe2-t-Bu, 0.75 h, 85%; SiMe2Bn, 1.5 h, 78%.
This 1,2-silyl-migrative cyclization could be applied to stereoselective synthesis of trisubstituted
tetrahydropyrans. The acid-catalyzed reaction of 1-, 2-, or 3-substituted (Z)-5-silyl-4-nonen-1-ols 8
gave r-2,t-3,c-6-, r-2,t-3,t-5-, or r-2,t-3,c-4-trisubstituted tetrahydropyrans with high diastereo-
selectivity, respectively. (Z)-4-Alkyl-4-silyl-3-buten-1-ols 5 as well as 1 underwent the 1,2-silyl-
migrative cyclization to give 2-alkyl-3-silyltetrahydrofurans 6 with high trans-selectivity. This
silicon-directed cyclization was also available for the stereoselective synthesis of tri- and tetrasub-
stituted tetrahydrofurans.
In tr od u ction
to be useful for C-X bond formation, with some excep-
tions.4-6
It is well recognized that triorganosilyl groups strongly
stabilize â-carbenium ions by σ-π orbital interaction.2
The â-effect is considerably valuable for regio- and
stereocontrolled C-X (X ) C, H, or heteroatom) bond
formation. In particular, electrophilic substitution reac-
tions with allylsilanes and vinylsilanes have been exten-
sively utilized as highly selective allylation and vinylation
methods.3 Because of the â-effect, electrophiles react with
the γ-carbon in allylsilanes or the R-carbon in vinylsilanes
so as to form saturated â-silylcarbenium ions (e.g., R3-
Si-CHR1-C+HR2) in both cases. The cationic intermedi-
ates, which are thermodynamically stable, rapidly un-
dergo â-elimination of the silyl group by nucleophilic
attack of a counteranion or a solvent molecule to afford
allylation and vinylation products. On the basis of this
fact, the active carbon species had been considered not
In the past decade, however, it has turned out that
internal carbon and heteroatom nucleophiles add to
saturated â-silylcarbenium ions efficiently, and this
process serves for the stereoselective construction of
carbocycles and heterocycles.7-9 In the reactions involving
such a bond-forming process, the Lewis acid promoted
[2 + 2] and [3 + 2] cycloadditions of allylsilanes to
electron-deficient unsaturated bonds (CdY) have been
intensively studied by several research groups because
they provide powerful methods for highly stereoselective
(4) The use of unsaturated â-silylcarbenium ions (e.g., R3Si-CR1d
C+R2 or R1CHdC+-CHR2(SiR3)) arising from allenylsilanes and pro-
pargylsilanes for C-C, C.-O, or C-N bond formation was reported in
the 1980s. (a) Danheiser, R. L.; Carini, D. J .; Basak, A. J . Am. Chem.
Soc. 1981, 103, 1604. (b) Pornet, J .; Miginiac, L.; J aworski, K.;
Randrianoelina, B. Organometallics 1985, 4, 333. See also ref 3b.
(5) Nucleophilic addition of halide ions to â-silylcarbenium ions
generated from allylsilanes and vinylsilanes: (a) Sommer, L. H.; Tyler,
L. J .; Whitmore, F. C. J . Am. Chem. Soc. 1948, 70, 2872. (b) 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. (c) Koenig, K.
E.; Weber, W. P. Tetrahedron Lett. 1973, 2533. (d) Miller, R. B.;
McGarvey, G. J . Org. Chem. 1978, 43, 4424.
(6) [2 + 2] Cycloadditions of allylsilanes to highly activated unsatur-
ated bonds was reported in the 1970s. These reactions may proceed
via saturated â-silylcarbenium ions. (a) Au-Yeung, B. W.; Fleming, I.
J . Chem. Soc., Chem. Commun. 1977, 81. (b) Abel, E. W.; Rowley, R.
J . J . Organomet. Chem. 1975, 84, 199. (c) De´le´ris, G.; Dunogun˜`ı, J .;
Calas, R. J . Organomet. Chem. 1976, 116, C45.
(1) Organosilicon Chemistry. 157. For part 156, see: Miura, K.;
Ootsuka, K.; Suda, S.; Nishikori, H.; Hosomi, A. Synlett 2002, 313.
(2) (a) Lambert, J . B. Tetrahedron 1990, 46, 2677. (b) Bassindale,
A. R.; Taylor, P. G. In The Chemistry of Organic Silicon Compounds;
Patai, S., Rappoport, Z., Ed.; Wiley: Chichester, 1989; Part 2, p 893.
(3) (a) Fleming, I.; Barbero, A.; Walter, D. Chem. Rev. 1997, 97,
2063. (b) Panek, J . S. In Comprehensive Organic Synthesis; Trost, B.
M., Ed.; Pergamon Press: Oxford, 1991; Vol. 1, p 579. (c) Fleming, I.
In Comprehensive Organic Synthesis; Trost, B. M., Ed.; Pergamon
Press: Oxford, 1991; Vol. 2, p 563. (d) Fleming, I.; Dunogun˜`ı, J .;
Smithers, R. Org. React. 1989, 37, 57. (e) Hosomi, A. Acc. Chem. Res.
1988, 21, 200. (f) Colvin, E. W. Silicon in Organic Synthesis; Butter-
worth: London, 1981.
(7) Reviews: (a) Kno¨lker, H.-J . J . Prakt. Chem. 1997, 339, 304. (b)
Masse, C. E.; Panek, J . S. Chem. Rev. 1995, 95, 1293.
10.1021/jo026006j CCC: $22.00 © 2002 American Chemical Society
Published on Web 07/25/2002
6082
J . Org. Chem. 2002, 67, 6082-6090

1,2-Silyl-Migrative Cylization
SCHEME 1
SCHEME 2
construction of four- and five-membered rings. The
silicon-directed cycloadditions are believed to proceed via
a stepwise mechanism shown in Scheme 1. The first step
is nucleophilic addition of an allylsilane to an electron-
deficient unsaturated bond activated by a Lewis acid. The
â-silylcarbenium ion intermediate formed is directly
cyclized to a four-membered ring by intramolecular
nucleophilic addition; otherwise, it is converted to another
â-silylcarbenium ion by 1,2-silyl migration, then cyclized
to a five-membered ring.
A number of the bond-forming reactions of â-silylcar-
benium ions arising from allylsilanes have been re-
ported,5-9 while similar reactions utilizing the reactivity
of vinylsilanes remain to be unexplored.5,10 Previously,
we have reported that, in the presence of an acid catalyst,
vinylsilanes 1 (R ) H) bearing a hydroxy group are
smoothly converted into tetrahydrofurans 3 via â-silyl-
carbenium ions generated by protonation of the R-carbon
(path a in Scheme 2).11,12 The silicon-directed cyclization
can be successfully utilized for the stereoselective syn-
thesis of disubstituted tetrahydrofurans. The intra-
TABLE 1. Scr een in g of Acid Ca ta lysts Usin g (Z)-1a a
yield (%)
trans-2a (E)-4a b 1a b
temp
(°C)
time
(h)
entry
catalyst
TiCl4
TiCl2(O-i-Pr)2
TsOH‚H2O
HCl gas
1
2
3
4
5
25
25
60
25
25
9.5
50
24
24
75
48
30
67
15
3
61
10
6
32
0
14
AcCl
30 (4.5)c 67 (83)
5 (5) 25 (6)
a
All reactions were performed with 1a (0.50 mmol), an acid
b
(0.025 mmol), and CHCl3 (2.5 mL) unless otherwise noted. Desi-
lylated product and unreacted substrate were obtained as a
mixture. Their yields were estimated by 1H NMR analysis. The
recovered substrate included its E-isomer as a minor component.
c
The values in parentheses are the results using 20 mol % AcCl.
molecular addition of a hydroxy group to vinylsilanes
proceeds in a stereospecific syn mode. Thus, we next
directed our efforts to the stereocontrolled introduction
of a side chain into the 2-position of the tetrahydrofuran
ring with R-alkylated vinylsilanes 1. Unexpectedly, the
acid-catalyzed cyclization of 1 (R ) alkyl) exclusively
formed tetrahydropyrans 2 without 3. Similar to the
Lewis acid promoted [3 + 2] cycloaddition of allylsilanes,
the formation of 2 would proceed via 1,2-silyl migration
of the initially formed â-silylcarbenium ion intermediate
(path b). We herein report the scope and mechanistic
aspects of this 1,2-silyl-migrative cyclization and its
application to the stereoselective synthesis of multi-
substituted tetrahydropyrans and tetrahydrofurans.13,14
(8) [3 + 2] and [2 + 2] cycloadditions of allylsilanes to unsaturated
bonds: (a) Kno¨lker, H.-J .; J ones, P. G.; Pannek, J .-B. Synlett 1990,
429. (b) Panek, J . S.; Yang, M. J . Am. Chem. Soc. 1991, 113, 9868. (c)
Danheiser, R. L.; Dixon, B. R.; Gleason, R. W. J . Org. Chem. 1992, 57,
6094. (d) Audran, G.; Monti, H.; Le´andri, G.; Monti, J .-P. Tetrahedron
Lett. 1993, 34, 3417. More recent reports: (e) Peng, Z.-H.; Woerpel K.
A. Org. Lett. 2001, 3, 675. (f) Akiyama, T.; Sugano, M.; Kagoshima, H.
Tetrahedron Lett. 2001, 42, 3889. (g) Panek, J . S.; Liu, P. J . Am. Chem.
Soc. 2000, 122, 11090. (h) Peng, Z.-H.; Woerpel K. A. Org. Lett. 2000,
2, 1379. (i) Roberson, C. W.; Woerpel, K. A. J . Org. Chem. 1999, 64,
1434. (j) Isaka, M.; Williard, P. G.; Nakamura, E. Bull. Chem. Soc.
J pn. 1999, 72, 2115. (k) Kno¨lker, H.-J .; J ones, P. G.; Wanzl, G. Synlett
1998, 613. (l) Akiyama, T.; Hoshi, E.; Fujiyoshi, S. J . Chem. Soc., Perkin
Trans 1 1998, 2121. (m) Akiyama, T.; Yamanaka, M. Tetrahedron Lett.
1998, 39, 7885. (n) Groaning, M. D.; Brengel, G. P.; Meyers, A. I. J .
Org. Chem. 1998, 63, 5517.
(9) Other types of nucleophilic addition to â-silylcarbenium ions
generated from allylsilanes: (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) Adiwidjaja, G.; Flo¨rke, H.;
Kirschning, A.; Schaumann, E. Liebigs Ann. 1995, 501. (d) Akiyama,
T.; Nakano, M.; Kanatani, J .; Ozaki, S. Chem. Lett. 1997, 385. (e)
Brocherieux-Lanoy, S.; Dhimane, H.; Poupon, J .-C.; Vanucci, C.;
Lhommet, G. J . Chem. Soc., Perkin Trans. 1 1997, 2163. (f) Monti, H.;
Rizzotto, D.; Le´andri, G. Tetrahedron 1998, 54, 6725. (g) Akiyama, T.;
Asayama, K.; Fujiyoshi, S. J . Chem. Soc., Perkin Trans 1 1998, 3655.
(h) Akiyama, T.; Ishida, Y. Synlett 1998, 1150. 1999, 160. (i) Akiyama,
T.; Ishida, Y.; Kagoshima, H. Tetrahedron Lett. 1999, 40, 4219. (j)
Sugita, Y.; Kimura, Y.; Yokoe, I. Tetrahedron Lett. 1999, 40, 5877. (k)
Angle, S. R.; El-Said, N. A. J . Am. Chem. Soc. 1999, 121, 10211.
(10) (a) Brook, M. A.; Sebastian, T.; J ueschke, R.; Dallaire, C. J .
Org. Chem. 1991, 56, 2273. (b) Brook, M. A.; Henry, C.; J ueschke, R.;
Modi, P. Synlett 1993, 97. (c) Yamazaki, S.; Tanaka, M.; Yamabe, S.
J . Org. Chem. 1996, 61, 4046.
Resu lts a n d Discu ssion
Cycliza tion of Vin ylsila n es 1 a n d 5. For the screen-
ing of acid catalysts, (Z)-1a was initially selected as a
substrate (Table 1). Treatment of (Z)-1a with 5 mol %
TiCl4 in CHCl3 at room temperature gave trans-2,3-
disubstituted tetrahydropyran 2a in 75% yield along with
desilylated product (E)-4a (entry 1). The cis-isomer of 2a
(13) For 1,2-silyl-migrative cycloadditions forming tetrahydrofurans,
see: (a) Panek, J . S.; Beresis, R. J . Org. Chem. 1993, 58, 809. (b)
Akiyama, T.; Ishikawa, K.; Ozaki, S. Chem. Lett. 1994, 627. (c)
Schinzer, D.; Panke, G. J . Org. Chem. 1996, 61, 4496. See also ref
8b,g,h.
(14) For preliminary papers on this work, see: (a) Miura, K.; Hondo,
T.; Saito, H.; Ito, H.; Hosomi, A. J . Org. Chem. 1997, 62, 8292. (b)
Miura, K.; Hondo, T.; Takahashi, T.; Hosomi, A. Tetrahedron Lett.
2000, 41, 2129.
(11) (a) Miura, K.; Okajima, S.; Hondo, T.; Nakagawa, T.; Takahashi,
T.; Hosomi, A. J . Am. Chem. Soc. 2000, 122, 11348. (b) Miura, K.;
Okajima, S.; Hondo, T.; Hosomi, A. Tetrahedron Lett. 1995, 36, 1483.
(c) Miura, K.; Hondo, T.; Okajima, S.; Hosomi, A. Tetrahedron Lett.
1996, 37, 487.
(12) Schaumann et al. also reported a similar type of cyclization in
1995. See ref 9c.
J . Org. Chem, Vol. 67, No. 17, 2002 6083

Miura et al.
TABLE 2. Effects of Silyl Gr ou p on Rea ctivitya
desilylation and exhibited much lower reactivity than (Z)-
1a (entry 3). On the other hand, the cyclization of (Z)-1d
(Si ) TBDMS) effected not only high yield of 2d but also
fast reaction rate (entry 4). A similar high reactivity was
observed in the case with (Z)-1e (Si ) SiMe2Bn (BnDMS),
entry 5). However, these substrates led to lower trans-
selectivity of 2 (trans/cis ) 95/5) in addition to the
formation of tetrahydrofurans (2R*,1′S*)-3. As shown in
eq 1, lowering the reaction temperature to 0 °C improved
vinylsilane 1
yield (%)
(E)-4a b 1b,c
time
(h) trans-2
entry
R1
R2
3
1
2
3
4
5
6
7
8
Ph
Me
Ph
t-Bu
Bn
Me (Z)-1a
Me (Z)-1b
Ph (Z)-1c 24
Me (Z)-1d
Me (Z)-1e
Me (Z)-1f
9.5
7.5
75
66
58
85d
78d
57
53
39
0
0
0
15
26
13
8
17
20
28
6
6
0
25
0
0.8
5e,f
1e,f
0
1.5
9.5
9.5
9.5
4
p-MeC6H4
p-MeOC6H4 Me (Z)-1g
p-CF3C6H4 Me (Z)-1h
12
15
49
0
0
the yield and trans-selectivity of 2d (90%, trans/cis ) 97/
3) with the inhibition of direct cyclization to 3d and
protiodesilylation to (E)-4a . The use of TiCl2(O-i-Pr)2 as
catalyst completely suppressed the formation of 3d to
bring about a better yield of trans-2d . The TiCl2(O-i-Pr)2-
catalyzed system at 0 °C was also effective in the
stereoselective cyclization of (Z)-1e, although it could not
suppress the formation of 3e.
a
All reactions were performed with a vinylsilane (0.50 mmol),
TiCl4 (0.025 mmol), and CHCl3 (2.5 mL) at room temperature
b
(method A). Desilylated product and unreacted substrate were
obtained as a mixture. Their yields were estimated by 1H NMR
analysis. c Z/E ratios of 1: 83/17 (entry 1), 92/8 (entry 3), 61/39
d
(entry 5), >99/1 (entries 6-8). The formation of cis-2 was
observed. The trans/cis ratios were 95/5 in both cases. e The
cyclized products 2 and 3 were obtained as a mixture. The yields
and isomeric ratio were determined by GC analysis. f (2R*,1′S*)-
Isomer was formed predominantly.
The electronic effect of substituent R1 on the reactivity
was investigated by the cyclization of (Z)-1f-h (Table 2).
As a result, it turned out that electron-donating p-tolyl
and p-anisyl groups accelerated the protiodesilylation to
(E)-4a (entries 6 and 7), while the electron-withdrawing
p-trifluoromethylphenyl group considerably diminished
the reactivity of the C-C double bond to prevent the
conversion of (Z)-1h (entry 8). The latter result implies
that protonation of the sp2 carbon R to the silyl group is
the rate-determining step of the present cyclization (vide
infra).
1
was not detected by H NMR (270 Hz) analysis. TiCl2-
(O-i-Pr)2 also promoted the cyclization with less catalytic
activity (entry 2). The use of TsOH‚H2O at 60 °C, which
was effective in the cyclization of R-unsubstituted (Z)-
vinylsilanes 1 (R ) H) (path a in Scheme 2),11 markedly
reduced the yield of trans-2a , and a considerable amount
of (E)-4a was formed (entry 3). Acetic acid, SnCl4, BF3‚
OEt2, Sc(OTf)3, and Sn(OTf)2 hardly induced the cycliza-
tion. HCl gas and AcCl as well as TiCl4 were good
catalysts for this cyclization (entries 4 and 5). An
increased amount of AcCl (20 mol %) provided trans-2a
in 83% yield. AcCl would serve as a source of HCl by the
reaction with the hydroxy group of (Z)-1a or EtOH
included in the solvent as a stabilizer (0.4-0.8% EtOH
in CHCl3), because 2,6-di-tert-butylpyridine (DTBP, 5 mol
%), a proton scavenger,15 prevented the AcCl-catalyzed
cyclization. Similarly, in the TiCl4-catalyzed system,
there is a possibility that HCl generated from TiCl4 is
the actual catalyst. As shown in Table 1, TiCl4 exhibited
higher catalytic activity than HCl gas and AcCl; however,
addition of DTBP (5 mol %) decelerated the TiCl4-
catalyzed cyclization of (Z)-1a although the yield of trans-
2a was still good (5 mol % TiCl4, 72 h, 80%). A part of
TiCl4 may work as a source of HCl.
The change in the geometry of 1 resulted in a marked
decrease in both the reactivity and stereoselectivity (eq
2). Under the standard reaction conditions (method A)
shown in Table 2, (E)-1a was converted into 2a in only
17% yield with low cis-selectivity. Similarly, the reaction
of (E)-1e gave a disappointing result. The cyclization of
(E)-1d was much faster than that of (E)-1a , affording 2d
in a good yield with higher cis-selectivity. In this case,
(2R*,1′R*)-3d was obtained as a byproduct in 8% yield.
Thus, the results of Table 2 and eq 2 indicate that both
the 1,2-silyl-migrative and direct cyclizations proceed in
a stereospecific manner.
The silyl group of (Z)-1 strongly affected the cyclization
efficiency and rate (Table 2). The TiCl4-catalyzed reaction
of vinylsilane (Z)-1b (Si ) TMS) resulted in slightly lower
yield of 2b because (Z)-1b was more sensitive to pro-
tiodesilylation than (Z)-1a (entries 1 and 2). To suppress
the desilylation, a more bulky silyl group such as Si-
MePh2 and TBDMS was employed.16 Contrary to our
expectation, (Z)-1c (Si ) SiMePh2) suffered considerable
To examine the applicability in terms of the R-sub-
stituent R, the TiCl4-catalyzed reactions of vinylsilanes
(16) It is well-known that the use of a sterically demanding silyl
group suppresses desilylation of â-silylcarbenium ion intermediates.
Kno¨lker, H.-J .; Foitzik, N.; Goesmann, H.; Graf, R. Angew. Chem., Int.
Ed. Engl. 1993, 32, 1081.
(15) Kostikov, R. R. In Encyclopedia of Reagents for Organic
Synthesis; Paquette, S. Ed.; Wiley: Chichester, 1995; Vol. 3, p 1623.
6084 J . Org. Chem., Vol. 67, No. 17, 2002

1,2-Silyl-Migrative Cylization
TABLE 3. Effects of r-Su bstitu en t on Rea ctivity
TABLE 4. Cycliza tion of (Z)- a n d (E)-Vin ylsila n es 5a
vinylsilane 1
yield (%)
entry
R
time (h)
trans-2
3
1
2
3
4
5
6
7
Bu
Me
(CH2)3OBn
(CH2)3OAc
Ph
(Z)-1a
9.5
15
15
47
24
75
76
72
72
0a
0b
0
0
0
0
0
0
0
(Z)-1i
(Z)-1j
(Z)-1k
(Z)-1l
(E)-1m
(Z)-1n
vinylsilane 5
yield (%)
6 (t/c)b 7c 5c,d
46 (>99/1) 37
63 (>99/1) 16 16
entry R1 config
methoda time (h)
1
2
3
4
5
6
7
8
9
Ph
Ph
t-Bu
t-Bu
Bn
Bn
Ph
Ph
Z
Z
Z
Z
Z
Z
E
E
E
E
E
E
5a
5a
5b
5b
5c
5c
5a
5a
5b
5b
5c
5c
A
B
A
B
A
B
A
B
A
B
A
B
49
36
4
8
Br
SiMe3
24
13
67 (1/1)c
89 (96/4)
95 (>99/1)
90 (99/1)
91 (99/1)
15 (9/91)
0
0
e
e
6
4
e
e
a
14
13
19
50
50
98
41
22
13
Desilylated product 4l was obtained in 29% yield. The sub-
strate was recovered in 30% yield. See the text. c Isomeric ratio
of 3n .
b
11 66
14 (21/79) 20
6
45
2
t-Bu
t-Bu
Bn
27 (9/91)
88 (4/96)
33 (5/95)
66 (2/98)
9
4
9
1i-m were carried out (Table 3). The present cyclization
tolerated polar functionalities such as ether and ester
groups (entries 3 and 4). Vinylsilane (Z)-1l (R ) Ph) was
not cyclized at all because of fast desilylation (entry 5).
In the case where R is a bromine atom, the substrate
(E)-1m was recovered quantitatively (entry 6). The
insensitivity of (E)-1m is presumably a result of the
inductive effect of the electron-negative bromine atom,
which would lower electron density of the C-C double
bond to prevent the initial protonation step of the present
cyclization. Interestingly, the use of (Z)-1n (R ) SiMe3)
gave only the direct cyclization product 3n as a 1:1
diastereomeric mixture (entry 7).
10
11
12
52
Bn
13 14
a
Method B: TsOH‚H2O (5 mol %) was used as catalyst at 60
b
°C. Other conditions are similar to those in method A. The
isomeric ratio was determined by GC analysis. c Byproduct 7 and
substrate 5 were obtained as a mixture. The yields were estimated
1
by H NMR analysis. The recovered 5 included another isomer as
d
a minor component. Desilylation of (Z)-5 and (E)-5 gave (E)-7
and (Z)-7, respectively. e Not determined.
SCHEME 3
Vinylsilanes 5, whose methylene tether is shorter than
that of 1 by one carbon, also underwent the acid-
catalyzed 1,2-silyl-migrative cyclization to afford 2,3-
disubstituted tetrahydrofurans 6 (Table 4). Treatment of
(Z)-5a with 5 mol % TiCl4 at room temperature for 49 h
gave trans-6a in a moderate yield (entry 1). Thus, (Z)-
5a was much less reactive than (Z)-1a . AcCl was not
suitable for this cyclization (102 h, 37%). However, the
use of TsOH‚H2O at 60 °C (method B) improved the yield
of 6a to some extent (entry 2). Similar to the case with
(Z)-1, the introduction of TBDMS or BnDMS as a silyl
group remarkably increased both the cyclization ef-
ficiency and rate (entries 3-6). Vinylsilane (Z)-5d , bear-
ing an ether functionality, also could be converted into
trans-6d in 64% yield, although it took prolonged reaction
time (eq 3). In both catalytic systems, the cyclization of
group of (Z)-1 or (Z)-5 forms oxonium ion A. (2) The
proton on the oxygen atom adds to the R-carbon. (3) The
resultant â-silyl carbenium ion B, which may be a
transition state, turns to its conformer C stabilized by
σ-π conjugation at the least motion.17 (4) C is converted
into another â-silyl carbenium ion D by 1,2-silyl migra-
tion.18 (5) Intramolecular attack of the oxygen from the
opposite side to the silyl group gives trans-2 or trans-6
and regenerates the proton or the Lewis acid. The direct
(E)-5a resulted in low efficiency, but it exhibited cis-
selectivity higher than that of (E)-1a (entries 7 and 8).
The TsOH-catalyzed cyclization of (E)-5b,c brought about
much better yield and cis-selectivity (entries 10 and 12).
Mech a n istic Asp ect of Cycliza tion of Vin ylsila n es
1 a n d 5. On the basis of the previous and present
results,11 a plausible mechanism for the trans-selective
cyclization of (Z)-1 and (Z)-5 is shown in Scheme 3. The
mechanism consists of the following five steps: (1) The
attachment of a proton or a Lewis acid to the hydroxy
(17) As mentioned by Koenig and Weber, simultaneously with
protonation to the double bond, rotation would occur about the
developing carbon-carbon single bond in the direction to permit the
silyl group to continuously stabilize the incipient â-silylcarbenium ion
B by hyperconjugation of the Si-C bond. Koenig, K. E.; Weber, W. P.
J . Am. Chem. Soc. 1973, 95, 3416.
J . Org. Chem, Vol. 67, No. 17, 2002 6085

Miura et al.
SCHEME 4
double bond and an electron-donative silyl group such
as TBDMS. Similar rate-accelerating effects have been
observed in the cyclization of R-unsubstituted vinylsi-
lanes 1 (R ) H) to tetrahydrofurans 3.11 These observa-
tions can be properly rationalized by the rate-determining
protonation of A (A′) to C (C′). The high reactivity of (Z)-
isomers probably originates from the steric repulsion
between the methylene tether and the silyl group in A
and B, which would promote the protonation process from
A to C. In contrast, the torsional interaction between the
methylene tether and R would decelerate the process
from A′ to C′, resulting in the low cyclization rate of (E)-
vinylsilanes. The rate-acceleration by a TBDMS group
is attributable to its relatively electron-donative charac-
ter,20 which would facilitate the protonation process by
enhancing the HOMO level of the C-C double bond.
Two possibilities can be considered for the origin of the
preferred formation of 2 to 3. One is the isomerization of
3 to 2 (thermodynamic control), and the other is that the
cyclization of D or D′ is faster than that of C or C′ (kinetic
control). To ascertain the former possibility, (2R*, 1′S*)-
3d and its diastereomer were prepared from 4-pentyn-
1-ol (see Supporting Information) and subjected to a
catalytic amount of TiCl4. Indeed, their isomerization to
2d rapidly proceeded with inverse stereoselectivity (eq
4).21 The stereospecific conversion agrees well with the
cyclization of C (n ) 1) without 1,2-silyl migration and
the desilylation of C and D give (2R*,1′S*)-3 and (E)-4
or (E)-7, respectively. The route to trans-2 may involve
initial formation of (2R*,1′S*)-3 followed by acid-cata-
lyzed isomerization via C and D (vide infra).
Intermolecular direct protonation of the substrate (step
1′) also is a possible process. However, the reaction path
via A provides a reasonable explanation for the stereo-
chemical outcomes in the stereoselective synthesis of
trisubstituted tetrahydropyrans and tetrahydrofurans
(vide infra). In our previous study on the cyclization of
R-unsubstituted vinylsilanes 1 (R ) H), we have proposed
the intramolecular protonation via A to rationalize the
observed asymmetric induction.11
The presence of an alkyl group as the R-substituent R
is essential to the present 1,2-silyl-migrative cyclization.
This fact suggests that the stabilization of carbenium ion
D by the alkyl group induces the 1,2-silyl migration (step
4) as mentioned by Danheiser et al.19 In the cyclization
of 1n , the lower stabilizing ability of the TMS group to
R-carbenium ions would inhibit the 1,2-silyl migration
of C.2 The nonstereoselective formation of 3n implies a
rapid equilibrium between C (R ) SiMe3) and C′′.
The cis-selective cyclization of (E)-1 and (E)-5 can be
rationalized by a similar mechanism (Scheme 4), in which
intramolecular protonation of oxonium ion A′ forms
â-silyl carbenium ion intermediate C′ via B′ and then C′
undergoes 1,2-silyl migration and intramolecular addi-
tion of the oxygen nucleophile to give cis-2 or cis-6. As
shown above, the stereoselectivity with (E)-vinylsilanes
is lower than that with the corresponding (Z)-isomers.
This result may be due to the fast rotation of â-silylcar-
benium ion D′ to D assisted by the steric interaction
between R and the methylene tether.
mechanism shown in Schemes 3 and 4. This result
discloses that 2d is a thermodynamically favored product.
In addition, MM2 calculation of the steric energy indi-
cates that trans-2d is more stable than (2R*,1′S*)-3d by
3.5 kcal/mol in their optimized structures.22
To examine which product (2 or 3) is kinetically
favored, the TiCl4- or TiCl2(Oi-Pr)2-catalyzed cyclization
of (Z)-1d was carried out at 0 °C. As a result, the major
product was trans-2d even at low conversion. However,
this observation does not necessarily prove that trans-
2d is kinetically favored because of the fast isomerization
of (2R*,1′S*)-3d to trans-2d . Electrophilic heteroatom
cyclization of 5-alkyl-4-penten-1-ols, which appears to
proceed via a transition state similar to that proposed
in the present cyclization, usually provides tetrahydro-
furans (5-exo products) rather than tetrahydropyrans (6-
endo products).23 This fact implies that tetrahydrofurans
3 are kinetic products. As described below, we found an
example that a tetrahydrofuran product was formed
The cyclization rate of vinylsilanes 1 and 5 (R ) alkyl)
was effectively enhanced by the (Z)-geometry of the C-C
(20) (a) Mayr, H.; Patz, M. Angew. Chem., Int. Ed. Engl. 1994, 33,
938. (b) Brengel, G. P.; Meyers, A. I. J . Org. Chem. 1996, 61, 3230.
(21) Ring contraction and enlargement via 1,2-silyl migration: (a)
Hudrlik, P. F.; Hudrlik, A. M.; Nagendrappa, G.; Yimenu, T.; Zellers,
E. T.; Chin, E. J . Am. Chem. Soc. 1980, 102, 6896; correction J . Am.
Chem. Soc. 1982, 104, 1157. (b) Tanino, K.; Yoshitani, N.; Moriyama,
F.; Kuwajima, I. J . Org. Chem. 1997, 62, 4206.
(22) The strain energy of tetrahydrofuran is higher than that of
tetrahydropyran by 5.4 kcal/mol and lower than that of oxetane by
19.8 kcal/mol. Isaacs, N. S. Physical Organic Chemistry; Wiley: New
York, 1987.
(18) There is a long-standing dispute on the structure of â-silylcar-
benium ions, which can take a hyperconjugatively stabilized open form
or a bridged form. Although the open forms C and D are employed in
Scheme 3, they can be displaced to one bridged form without any
problems. (a) Lambert, J . B.; Zhao, Y. J . Am. Chem. Soc. 1996, 118,
7867. (b) Ibrahim, M. R.; J orgensen, W. L. J . Am. Chem. Soc. 1989,
111, 819. See also ref 2.
(19) Danheiser, R. L.; Takahashi. T.; Berto´k, B.; Dixon, B. R.
Tetrahedron Lett. 1993, 34, 3845.
(23) Harding, K. E.; Tiner, T. H. In Comprehensive Organic Syn-
thesis; Trost, B. M., Ed.; Pergamon Press: Oxford, 1991; Vol. 4, p 363.
6086 J . Org. Chem., Vol. 67, No. 17, 2002

1,2-Silyl-Migrative Cylization
TABLE 5. Cycliza tion of (Z)-Vin ylsila n es 8
(Z)-vinylsilane 8
yield (%)
entry
R
R1
R2
R3
methoda
time (h)
9 (t/c)b,c
10 (t/c)b,d
1
2
3
Ph
t-Bu
Bn
Ph
Ph
Ph
Ph
Bn
Bn
Ph
Ph
Ph
Ph
Ph
Ph
Bn
Bn
Ph
Ph
Ph
Ph
Ph
Me
Me
i-Pr
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Ph
Ph
Ph
Me
Me
i-Pr
i-Pr
i-Pr
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
8a
8b
8c
8d
8d
8e
8f
8g
8g
8h
8h
8i
8i
8i
8j
8k
8k
8l
A
A
A
A
Cf
A
A
A
C
A
C
A
C
C
A
A
C
A
Cf
28
2
2
24
24
11
24
2
7.5
9
27
3
2.5
0.5
34
23
72
96
76
59 (<1/99)
91 (29/71)
78 (9/91)
71 (16/84)
52 (3/97)
0
0
0
0
0
0
0
0
4
5e
6e
7
76 (7/93)
70 (93/7)
8
9
74 (85/15)g
19 (>99/1)g
66 (88/12)
90 (89/11)
76 (96/4)
73 (19/81)g
0
0
3 (<1/99)
72 (8/92)
41 (6/94)
12 (>99/1)
18 (>99/1)g,h
14 (>99/1)g,h
42 (>99/1)
68 (>99/1)
10
11
12
13
14e
15e
16e
17e
18
19
22 (>99/1)
2 (>99/1)
16 (<1/99)
33 (<1/99)g
2 (<1/99)g
18 (<1/99)
2 (<1/99)
Ph
Ph
Ph
Peni
Peni
8l
a
b
Method C: AcCl was used as catalyst. Other conditions were identical with those in method A. The isomeric ratio was determined
by 270 MHz 1H NMR analysis. The ratios >99/1 and <1/99 mean that no isomer is detected by 1H NMR analysis. In entries 9, 12-15,
and 17-19, 9 and 10 were obtained as a mixture. Their yields were estimated by 1H NMR analysis. c The ratio is concerned with the
relative configuration between the butyl and R1 (entries 1-6), R2 (entries 7-14), or R3 groups (entries 15-19). The ratio is concerned
d
with the relative configuration between the 1-silylpentyl and R2 (entries 9 and 12-14) or R3 groups (entries 15-19). e Recovery of the
substrate (%): 20 (entry 5), 10 (entry 6), 55 (entry 14), 47 (entry 15), 17 (entry 16), 83 (entry 17). The recovered substrate included the
E-isomer as a minor component. f With 20 mol % AcCl. The ratio was determined by GC analysis. (2R*,3S*,1′S*)-10k /(2R*,3S*,1′R*)-
g
h
i
10k ) 93/7 (entry 16) and 97/3 (entry 17). Pen ) pentyl.
predominantly and gradually isomerized to the corre-
sponding tetrahydropyran by the action of an acid
catalyst.
In the cyclization of 5, oxetane products were not
formed at all. This observation is attributable to their
intrinsic angle strain, which would retard the cyclization
of â-silylcarbenium ion intermediates C (C′) (n ) 0) to
oxetanes or strongly accelerate the isomerization of
oxetanes to tetrahydrofurans 6.24
pyrans 9a -e as major diastereomers along with their
r-2,t-3,t-6-isomers (entries 1-6 in Table 5). Vinylsilane
8a exhibited high 2,6-cis-selectivity, although the yield
of 9a was not so good as a result of protiodesilylation
(entry 1). As expected, the introduction of a TBDMS or
BnDMS group raised the cyclization rate and the yield
of 9, but the stereoselectivity dropped (entries 2 and 3).
The use of AcCl as catalyst was effective in improving
the 2,6-cis-selectivity with 8d (entry 5).
Ster eoselective Syn th esis of High ly Su bstitu ted
Tetr a h yd r op yr a n s a n d Tetr a h yd r ofu r a n s. Recently,
much attention has been paid to the stereoselective
synthesis of substituted oxygen-containing heterocycles
since tetrahydropyran and tetrahydrofuran units are
frequently found in polyether antibiotics and other
biologically active natural products.25 Therefore, we at-
tempted to apply the present 1,2-silyl-migrative cycliza-
tion to the stereoselective synthesis of trisubstituted
tetrahydropyrans and tetrahydrofurans using (Z)-5-silyl-
4-nonen-1-ols and (Z)-4-silyl-3-octen-1-ols with a sub-
stituent on the methylene tether (8 and 11).
The TiCl4-catalyzed reaction of 8f-i formed 2,3,5-
trisubstituted tetrahydropyrans 9f-i with good to high
2,5-trans-selectivity (entries 7, 8, 10, and 12). Vinylsilane
8i, bearing an isopropyl group as R2, showed reactivity
much higher than that of 8f and 8h (entry 12). The bulky
substituent would accelerate the rate-determining pro-
tonation by raising the energy of the ground state relative
to the transition state as in the gem-dimethyl effect.26
The cyclization of 8i also gave tetrahydrofuran 10i as a
byproduct. The AcCl-catalyzed system prevented pro-
tiodesilylation of 8h to achieve a high yield of 9h (entry
11). Interestingly, the AcCl-catalyzed reactions of 8g,i
gave 10g,i in preference to 9g,i (entries 9 and 13). The
ratio of 10i to 9i at 45% conversion of 8i (0.5 h) was
higher than that at the complete conversion (entry 14).
This fact indicates that 10i is isomerized to 9i under the
reaction conditions. To confirm the isomerization, a
mixture of 10i (major component) and 9i was treated with
The cyclization of 8a -e with a catalytic amount of
TiCl4 or AcCl gave r-2,t-3,c-6-trisubstituted tetrahydro-
(24) Akiyama et al. have reported that, in the cycloaddition of
allylsilanes to ketones, the formation of oxetanes is a kinetically
favored path. Akiyama, T.; Kirino, M. Chem. Lett. 1995, 723.
(25) Reviews: (a) Boivin T. L. B. Tetrahedron 1987, 43, 3309. (b)
Cardillo, G.; Orena, M. Tetrahedron 1990, 46, 3321. (c) Kotsuki, H.
Synlett 1992, 97. (d) Harmange, J . C.; Figade´re, B. Tetrahedron:
Asymmetry 1993, 4, 1711. (e) Koert, U. Synthesis 1995, 115.
(26) (a) Allinger, N. L.; Zalkow, V. J . Org. Chem. 1960, 25, 701. (b)
Beckwith, A. L. J .; Zimmerman, J . J . Org. Chem. 1991, 56, 5791.
J . Org. Chem, Vol. 67, No. 17, 2002 6087

Miura et al.
TABLE 6. Acid -Ca ta lyzed Isom er iza tion of
Tetr a h yd r ofu r a n 10i
TABLE 7. Cycliza tion of (Z)-Vin ylsila n es 11
vinylsilane 11
R1 R2
yield (%)
method time (h) 12 (dr)a
2,5-t-9i/2,5-c-9i/t-10i/c-10i
entry
R
11b
catalyst
substratea
producta
yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Ph Ph
Ph Ph
Bn Ph
Bn Ph
Ph Hex
Ph i-Pr
Ph i-Pr
Ph i-Pr
H
H
H
H
H
H
H
H
Ph
Ph
Ph
Ph
11a
11a
11b
11b
11c
11d
11d
11d
11e
11e
11f
11f
11g
11g
A
B
A
B
B
A
B
48
55
37 (53/47) 55
AcCl
20/0/4/76
9/0/6/85
24/0/6/70
22/0/5/73
37/0/5/58
93/7/<1/<1
96
99
84
77 (51/49)
2
AcCl/1-hexanol (1:20)
TiCl4
6.5 78 (58/42) 13
6.5 91 (55/45)
58 87 (68/32)
35
22
168
82
124
21
76
38
115
72
4
4
a
Determined by 1H NMR analysis.
46 (74/26) 18
93 (69/31)
25 (77/23) 75
0
AcCl (Table 6). As a result, AcCl itself hardly induced
the isomerization; however, the combination of AcCl and
1-hexanol effected the partial conversion of 10i into 9i.
This observation suggests that HCl generated from AcCl
catalyzes not only the cyclization of 8i but also the
isomerization of 10i. The slow isomerization with AcCl
and 1-hexanol is consistent with the selective formation
of 10i in entry 13. As predicted from the result in entry
12, TiCl4 smoothly isomerized 10i to 9i (the last line of
Table 6). Thus, it is apparent that 9i and 10i are
thermodynamic and kinetic products, respectively, in the
AcCl-catalyzed system.
C
Ph
Ph
Bn
Bn
Ph
Ph
Ph
H
H
H
H
H
H
H
Ac
B
61 (4/96)
68 (<1/99)
62 (<1/99)
84 (<1/99)
65 (1/99)
55 (6/94)
34 (5/95)
20
9
0
5
8
Ac
B
Pen
Pen
c-Hex 11h
Ac
B
11
16
B
a
The isomeric ratio was determined by GC analysis. The
relative configurations of 12a -d were not determined. The major
b
isomers of 12e-h were 2,4-cis. Including E-isomer as a minor
component. c With 20 mol % TiCl4.
clearly show that the isomerization of (Z)-1a to (E)-1a is
much slower than the 1,2-silyl-migrative cyclization to
trans-2a and the protiodesilylation to (E)-4a . We have
also reported a similar observation in the cyclization of
R-unsubstituted (Z)-vinylsilane 1 (R ) H, Si ) SiMe2-
Ph).11 J udging from the slow isomerization and the strong
â-effect of silyl groups, the reversion of carbenium ion
intermediates C and D to A hardly occurs as a result of
the fast ring closure and desilylation. Accordingly, in the
cyclization of (Z)-vinylsilanes bearing a chiral center (8
and 11), the relative configurations of the newly formed
chiral centers should be determined in the protonation
step. In other words, the asymmetric induction observed
with 8 and 11 would originate from diastereoface-
selective protonation. It is very difficult to explain the
face-selective protonation with an intermolecular proto-
nation process such as step 1′ in Scheme 3, while
intramolecular protonation via an oxonium ion interme-
diate such as A easily rationalizes the origin of the
present asymmetric induction. For instance, in the cy-
clization of 8f-i, the intramolecular protonation would
proceed via Ech-eq, a chairlike conformation with a
pseudoequatorial substituent, because another chairlike
conformation Ech-ax is unfavored by the intrinsic non-
bonding interactions arising from the pseudoaxial sub-
stituent (Scheme 5). Then â-silylcarbenium ions F and
G formed from Ech-eq are cyclized to cis-10 and 2,5-t-9,
respectively. Similarly, the stereochemical outcomes with
8a -e and 8j-l are attributable to the intramolecular
protonation via chairlike conformations Hch-eq and Ich-eq
(Scheme 6). The high diastereoselectivity with 8j-l is
probably because the allylic 1,3-strain between the sub-
Vinylsilanes 8j-l, bearing a substituent at the allylic
position, were much less reactive toward the acid-
catalyzed cyclization than other vinylsilanes (entries 15-
19). The cyclization afforded a mixture of 9 and 10 in
low to moderate yield, and each cyclized product was a
single diastereomer with the exception of 10k . Indepen-
dently of the catalyst used, 8l underwent the direct
cyclization leading to 10l selectively (entries 18 and 19).
The TsOH-catalyzed cyclization of (Z)-vinylsilanes
11a -d gave tetrahydrofurans 12a -d in good to high
yields (entries 2, 4, 5, and 7 in Table 7). Unfortunately,
the diastereoselectivity with respect to the relative con-
figuration between the 2- and 5-positions was rather low.
Other acid catalysts, TiCl4 and AcCl, were not so effective
in improving the selectivity (entries 1, 3, 6, and 8). In
contrast, the cyclization of (Z)-vinylsilanes 11e-h , sub-
stituted at the allylic position, achieved high levels of 2,4-
cis-selectivity, although the substrates showed low reac-
tivity (entries 9-15). As shown in eqs 5 and 6, the present
stituent R3 and the silyl group strictly forbids the
cyclization was also applicable to the stereoselective
synthesis of tetrasubstituted tetrahydrofurans.
27
oxonium ion intermediate to take conformation Ich-ax
.
Or igin of Asym m etr ic In d u ction . In the TiCl4-
catalyzed reaction of (Z)-1a (entry 1 in Table 2), the yield
and Z/E ratio of the recovered 1a (6%, Z/E ) 83/17)
The origin of the low reactivity of 8j-l is not clear.
(27) Hoffmann, R. W. Chem. Rev. 1989, 89, 1841.
6088 J . Org. Chem., Vol. 67, No. 17, 2002

1,2-Silyl-Migrative Cylization
TABLE 8. Con ver sion of Silyl Gr ou p to Hyd r oxy
Gr ou p a
SCHEME 5
entry
substrate
trans-2a
trans-2e
trans-2j
9d (2,6-c/t ) 84/16)
2,5-t-9f
9i (2,5-t/c ) 96/4)
trans-6a
trans-6c
product
yield (%)
1
2b
3
4
5
13a
13a
13b
13c
13d
13e
14a
14a
14b
14c
88
82
84
57 (2,6-c) + 7 (2,6-t)
86
6
53 (2,5-t/c ) >95/5)
7
89
87
72
93
8b
9
2,4-c-12g
2,4-c-12j
10
a
Reagents and conditions: (1) t-BuOK (1.2 equiv), DMSO, rt,
7 h; (2) H2O2 (10 equiv), TBAF (3.6 equiv), KHCO3 (2 equiv),
b
MeOH, THF, 40 °C, 24 h. See ref 29b. The oxidation was
performed without pretreatment using t-BuOK and DMSO.
SCHEME 6
via L. Another conformer J ′ is energetically unfavorable
as a result of the 1,3-allylic strain between R2 and the
silyl group.27
Oxid a t ive Clea va ge of Silicon -Ca r b on Bon d .
Some silyl groups are known to be valuable as latent
hydroxy groups for the stereocontrolled synthesis of
alcohols.28,29 To enhance the synthetic utility of the
present cyclization, we examined oxidative cleavage of
the C-Si bond in the cyclized products (Table 8). Accord-
ing to the reported two-step procedure,29b a variety of
cyclic ethers having a dimethylphenylsilyl group could
be converted to the corresponding alcohols in moderate
to high yields. On the other hand, oxidative removal of a
BnDMS group could be performed in one step (entries 2
and 8). Thus, a BnDMS group not only effectively
accelerates the 1,2-silyl-migrative cyclization but also
works as an efficient hydroxy surrogate.14b
SCHEME 7
Con clu sion
We have found that the acid-catalyzed reaction of
R-alkylated (Z)-vinylsilanes 1 and 5 gives trans-2-alkyl-
3-silyl-disubstituted tetrahydropyrans 2 and tetrahydro-
furans 6, respectively, by intramolecular addition of the
hydroxy group. This observation stands in sharp contrast
to our previous observation that R-unsubstituted vinyl-
silanes 1 (R ) H) are cyclized to tetrahydrofurans 3.11
The present cyclization is a novel type of 1,2-silyl migra-
tion reaction via â-silylcarbenium ion intermediates; most
of the known 1,2-silyl migration reactions require more
than an equimolar amount of an acid promoter and are
usually utilized for the construction of five-membered
carbocycles and heterocycles.30 The 1,2-silyl-migrative
cyclization is applicable to the stereoselective synthesis
of highly substituted tetrahydropyrans and tetrahydro-
However, the low reactivity is likely to arise from the
nonbonding interaction between R3 and the silyl group
in the transition state of intramolecular protonation. The
repulsive interaction may also restrain the 1,2-silyl
migration leading to 2,4-c-9j-l.
The 2,4-cis-selectivity with 11e-h is explainable by
intramolecular protonation via J , a conformer of the
oxonium ion intermediate (Scheme 7). The protonation
forms â-silylcarbenium ion K, which turns to 2,4-c-12e-h
(28) Reviews: (a) Tamao K. In Advances in Silicon Chemistry;
Larson, G. L., Ed.; J AI Press Inc.: Greenwich, 1996; Vol. 3, p 1. (b)
J ones G. R.; Landais, Y. Tetrahedron 1996, 52, 7599. (c) Colvin, E. W.
In Comprehensive Organic Synthesis; Trost, B. M., Ed.; Pergamon
Press: Oxford, 1991; Vol. 7, p 641.
(29) (a) Tamao, K.; Ishida, N. J . Organomet. Chem. 1984, 269, C37.
(b) Murakami, M.; Suginome, M.; Fujimoto, K.; Nakamura, H.;
Andersson, P. G.; Ito, Y. J . Am. Chem. Soc. 1993, 115, 6487.
J . Org. Chem, Vol. 67, No. 17, 2002 6089

Miura et al.
-3.29 (CH3), 13.98 (CH3), 22.57 (CH2), 25.93 (CH2), 27.41 (CH2
× 2), 30.05 (CH), 36.07 (CH2), 68.38 (CH2), 79.70 (CH), 127.71
(CH × 2), 128.84 (CH), 133.75 (CH × 2), 138.62 (C); MS m/z
(relative intensity) 276 (M+, 0.6), 135 (100). Anal. Calcd for
furans. The stereochemical outcomes can be well ratio-
nalized by the diastereoface-selective intramolecular
protonation of oxonium ion intermediates. The cyclized
products having a dimethylphenylsilyl or BnDMS group
are readily accessible to the corresponding alcohols by
oxidative removal of the silyl group. In conclusion, the
present cyclization, a novel type of 1,2-silyl-migrative
cyclization, provides a powerful method for the stereo-
controlled synthesis of various tetrahydropyran and
tetrahydrofuran derivatives.
C
17H28OSi: C, 73.85; H, 10.21. Found: C, 73.63; H, 10.11.
Meth od B. TsOH‚H2O (4.8 mg, 0.025 mmol) was charged to
a reaction flask, and the flask was filled with N2. CHCl3 (2.5
mL) and (Z)-5a (132 mg, 0.501 mmol) were introduced to the
flask, and then the mixture was heated to 60 °C. After being
stirred for 10 h, the resultant solution was subjected to the
same workup as in method A. The crude product was chro-
matographed on silica gel (hexane-AcOEt, 10:1) to give trans-
2-butyl-3-dimethylphenylsilyltetrahydrofuran (trans-6a , 83
mg, 63%) and a mixture of (E)-3-octen-1-ol (7, 16%)32 and (Z)-
5a (16%). trans-6a : bp 80 °C (0.20 Torr, bath temp); IR (neat)
2955, 1426, 1249, 1111, 830, 733, 697 cm-1; 1H NMR (CDCl3)
δ 0.32 (s, 3H), 0.33 (s, 3H), 0.83 (t, J ) 7.1 Hz, 3H), 1.13-1.43
(m, 7H), 1.74 (ddt, J ) 11.9, 10.6, 7.9 Hz, 1H), 1.93-2.06 (m,
1H), 3.64-3.75 (m, 3H), 7.30-7.40 (m, 3H), 7.47-7.52 (m, 2H);
13C NMR (CDCl3) δ -4.26 (CH3), -4.18 (CH3), 13.98 (CH3),
22.70 (CH2), 28.72 (CH2), 29.74 (CH2), 31.61 (CH), 36.05 (CH2),
67.32 (CH2), 81.62 (CH), 127.82 (CH × 2), 129.15 (CH), 133.78
(CH × 2), 137.75 (C); MS m/z (rel intensity) 205 (M+ - C4H9,
48), 135 (100). Anal. Calcd for C16H26OSi: C, 73.22; H, 9.98.
Found: C, 73.01; H, 10.02. Meth od C. AcCl was used as
catalyst, and other operations are identical with those of
method A.
Exp er im en ta l Section
Gen er a l Meth od . Unless otherwise noted, all reactions and
distillations of solvents were carried out under N2. Solvents
were dried by distillation from sodium/benzophenone ketyl
(THF, Et2O), CaCl2-NaHCO3 (CHCl3 containing 0.4-0.8% of
ethanol), and CaH2 (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). Boiling points
indicated by air-bath temperature (bath temp) were deter-
mined with Kugelrohr distillation apparatus. 1H and 13C NMR
were recorded in CDCl3 at 270 and 67.7 MHz, respectively.
The chemical shifts (δ) are reported with reference at 0.00 ppm
(Me4Si) or 7.26 ppm (CHCl3) for the proton and at 77.00 ppm
(centered on the signal of CDCl3) for the carbon. The number
of protons on each carbon atom was definitely determined by
DEPT experiments.
Acid -Ca ta lyzed Cycliza tion of Vin ylsila n es (Typ ica l
P r oced u r e). Meth od A. TiCl4 (1.0 M in CH2Cl2, 25 µL, 0.025
mmol) was added to a solution of (Z)-1a (138 mg, 0.500 mmol)
in CHCl3 (2.5 mL) at room temperature. After being stirred
for 9.5 h, the mixture was poured into saturated aqueous
NaHCO3 (20 mL) and extracted with CH2Cl2 (2 × 10 mL). The
combined organic layer was dried over Na2SO4 and evaporated.
The crude product was chromatographed on silica gel (hex-
ane-AcOEt, 10:1) to give trans-2-butyl-3-dimethylphenyl-
silyltetrahydropyran (trans-2a , 103 mg, 75%) and a mixture
of (E)-4-nonen-1-ol (4, 15%)31 and 1a (6%, Z/E ) 83/17). trans-
2a : bp 140 °C (0.30 Torr, bath temp); IR (neat) 2950, 1458,
1428, 1377, 1249, 1104, 731, 699 cm-1; 1H NMR (CDCl3) δ 0.28
(s, 3H), 0.31 (s, 3H), 0.78 (t, J ) 6.9 Hz, 3H), 1.03-1.59 (m,
10H), 1.70-1.79 (m, 1H), 3.20 (ddd, J ) 10.6, 7.9, 2.5 Hz, 1H),
3.36 (td, J ) 10.9, 3.6 Hz, 1H), 3.92-4.00 (m, 1H), 7.32-7.38
(m, 3H), 7.44-7.53 (m, 2H); 13C NMR (CDCl3) δ -3.66 (CH3),
Ack n ow led gm en t. The present work was partly
supported by Grants-in-Aid for Scientific Research,
Grants-in-Aid for Scientific Research on Priority Areas
(no. 706, Dynamic Control of Stereochemistry) from the
Ministry of Education, Science, Sports and Culture,
J apan. This work was also partly supported by CREST,
Science and Technology Corporation (J ST). We thank
Dow Corning Toray Silicone Co. Ltd. and Shin-Etsu
Chemical Co. Ltd. for a gift of organosilicon compounds.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures for the synthesis of vinylsilanes and authentic samples
(3d , 10i, and 10l), acid-catalyzed isomerization of 2-(silyl-
methyl)tetrahydrofurans, and oxidative cleavage of silicon-
carbon bond; spectral data for all substrates, their synthetic
intermediates, and products; stereochemical assignment of the
cyclized products. This material is available free of charge via
the Internet at http://pubs.acs.org.
(30) For the formation of six-membered rings via 1,2-silyl migration,
see: (a) Danheiser, R. L.; Fink, D. M. Tetrahedron Lett. 1985, 26, 2513.
(b) Angle, S. R.; Boyce, J . P. Tetrahedron Lett. 1994, 35, 6461. See
also ref 21.
(31) Matsumoto, K.; Aoki, Y.; Oshima, K.; Utimoto, K. Tetrahedron
1993, 49, 8487.
J O026006J
(32) Vasil’ev, A. A.; Cherkaev, G. V.; Nikitina, M. A. Zh. Org. Khim.
1994, 30, 816.
6090 J . Org. Chem., Vol. 67, No. 17, 2002