Tin(II) trifluoromethanesulfonate-catalyzed highly selective synthesis of 2-substituted 4-methylenetetrahydropyrans from trimethyl{2-[2-(trimethylsiloxy)ethyl]allyl}silane and acetals

Article abstract of DOI:10.1246/bcsj.74.569

A variety of 2-substituted 4-methylenetetrahydropyrans are easily produced by the reaction of acetals with trimethyl{2-[2-(trimethylsiloxy)ethyl]allyl}silane under the influence of a catalytic amount of tin(II) trifluoromethanesulfonate.

Full text of DOI:10.1246/bcsj.74.569

Short Articles
Bull. Chem. Soc. Jpn., 74, 569–570 (2001) 569
lar to that for the synthesis of the silane 2.4
First, we undertook to examine the reaction of p-anisalde-
hyde dimethyl acetal (5) with trimethyl{2-[2-(trimethyl-
siloxy)ethyl]allyl}silane (4) according to the procedure of 2-
aryl-4-methylenetetrahydrofuran synthesis previously reported
by us.1 The desired product, 2-(4-methoxyphenyl)-4-methyl-
enetetrahydropyran (6), was obtained in 53% yield (Table 1,
Run 2). After a preliminary investigation in search of the opti-
mum catalyst and its molar ratio to the substrates, we have
found that tin(II) trifluoromethanesulfonate in a molar ratio be-
tween 0.05 to 0.1 to the acetal 5 gave the highest yield of the
product 6. However, a double bond isomer 7 was also obtained
in 3/97 to 12/88 molar ratio to 6 (Table 1, Runs 5–8).
The reaction was conducted at room temperature with vari-
ous dimethyl acetals including those of aromatic aldehydes, ar-
omatic ketones, aliphatic aldehydes, and aliphatic ketones.
Representative results are summarized in Table 2. As can be
seen, the reaction is successful for all of the acetals of both al-
dehydes and ketones. The cyclization products are mixtures of
double bond positional isomers 9, 10, and 11 with a consistent
preponderance of exocyclic isomers 9. Although these exocy-
clic double bond isomers could not be separated by silica gel
chromatography, we have found that this complexity of the
product can be conveniently evaded by lowering the reaction
temperature. Thus, the reaction performed at –78 °C (Table 2)
afforded exclusively the single cyclization products,5 exocyclic
isomers 9, in good yields without the appearance of double
bond isomers.6
Tin(II) Trifluoromethanesulfonate-
Catalyzed Highly Selective Synthesis
of 2-Substituted 4-Methylenetetra-
hydropyrans from Trimethyl{2-[2-
(trimethylsiloxy)ethyl]allyl}silane
and Acetals
Takeshi Oriyama,* Akihiro Ishiwata, and
Takeshi Suzuki
Faculty of Science, Ibaraki University, Bunkyo, Mito 310-
8512
(Received September 18, 2000)
A variety of 2-substituted 4-methylenetetrahydropyrans
are easily produced by the reaction of acetals with trimeth-
yl{2-[2-(trimethylsiloxy)ethyl]allyl}silane under the influ-
ence of a catalytic amount of tin(II) trifluoromethane-
sulfonate.
Our previous investigation1 documented the novel and con-
venient synthesis of 2-aryl-4-methylenetetrahydrofurans from
acetals and trimethyl[2-(trimethylsiloxymethyl)allyl]silane. In
In conclusion, the present one-step synthesis of 2-substitut-
ed 4-methylenetetrahydropyrans from acetals has these advan-
tageous features: 1) experimental convenience, 2) mild reac-
tion conditions, 3) single cyclization product, and 4) starting
from acetals, not from carbonyl compounds. Further work on
broadening the scope and synthetic applications of this novel
methodology is now in progress.
this reaction, the acetals 1 and the silane 2 act as geminal dica
-
tion equivalent and dianion equivalent of 4-atom unit, respec-
tively, to give directly the tetrahydrofurans 32 by a simple one-
pot procedure (Scheme 1). As a logical extension, we have en-
visioned a way to extend our new methodology to the synthesis
of 4-methylenetetrahydropyrans by the use of homologous si-
lane, trimethyl{2-[2-(trimethylsiloxy)ethyl]allyl}silane (4), in
place of trimethyl[2-(trimethylsiloxymethyl)allyl]silane (2).
On the other hand, Markó et al. reported a trimethylsilyl triflu-
oromethanesulfonate (TMSOTf)-catalyzed condensation of
bis-silylated reagent 4 with carbonyl compounds to give regio-
isomeric mixtures of dihydropyrans.3
Table 1. The Effect of Catalyst on the Reaction between
p-Anisaldehyde Dimethyl Acetal and Trimethyl{2-[2-
(trimethylsiloxy)ethyl]allyl}silanea)
Our expectation has been successfully realized, and in this
communication, we wish to describe an expedient method for
the highly selective synthesis of 2-substituted 4-methylene-
tetrahydropyrans from various acetals under mild conditions.
The starting homologous silane, trimethyl{2-[2-(trimethyl-
siloxy)ethyl]allyl}silane (4), was prepared from commercially
available alcohol, 3-methyl-3-buten-1-ol, by a procedure simi-
Run Catalyst (molar amounts) Time/h Yield/%
6 : 7b)
1
2
3
4
5
6
7
8
SnCl2 (0.05)
SnCl2 (0.1) AcCl (0.1)
SnBr2 (0.05)
1
4
1
1
0.5
4
0.5
0.5
0
53
0
—
100 : 0
—
ZnCl2 (0.05)
0
—
Sn(OTf)2 (0.05)
Sn(OTf)2 (0.05)
Sn(OTf)2 (0.1)
Sn(OTf)2 (0.01)
74
71
73
67
96 : 4
93 : 7
88 : 12
97 : 3
a) Molar ratio of acetal 5 : allylsilane 4 = 1 : 1.2. b) Determined by
Scheme 1.
1H NMR.

570 Bull. Chem. Soc. Jpn., 74, No. 3 (2001)
© 2001 The Chemical Society of Japan
Table 2. Synthesis of Various 4-Methylenetetrahydropyrans from Acetalsa)
Yield of
Run
R1R2C(OMe)2
Temp
Time/h
9 : 10 : 11b)
9 + 10 + 11/%
1
2
3
4
5
6
7
8
9
4-MeOC6H4CH(OMe)2
(E)-PhCH CHCH(OMe)2
Ph(CH2)2CH(OMe)2
PhC(OMe)2CH3
rt
−78 ◦C
rt
0.5
4
1
4
1
4
1
4
1
74c)
80
65
65
21
0
85
87
83
71
86
71
96 : 4 : 0
100 : 0 : 0
88 : 3 : 9
100 : 0 : 0
63 : 37 : 0
—
94 : 3 : 3
100 : 0 : 0
91 : 5 : 4
100 : 0 : 0
92 : 8 : 0
100 : 0 : 0
−78 ◦C
rt
−78 ◦C
rt
−78 ◦C
(n-Pr)2C(OMe)2
rt
10
11
12
−78 ◦C
rt
4
1
4
[-(CH2)5-]C(OMe)2
−78 ◦C
a) Molar ratio of acetal 8 : allylsilane 4 = 1 : 1.2. b) Determined by 1H NMR. c) Reaction was carried out for
0.5 h.
References
ture was stirred for 4 h at –78 °C and quenched with a saturated
aqueous sodium hydrogencarbonate. The organic materials were
extracted with dichloromethane and combined extracts were
washed with brine and dried over anhydrous sodium sulfate. The
solvent was evaporated and 2-(4-methoxyphenyl)-4-methylenetet-
rahydropyran (39.9 mg, 80%) was isolated by thin-layer chroma-
tography on silica gel. 1H NMR (400 MHz, CDCl3) δ 7.29 (d, J =
8.8 Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H), 4.79 (dd, J = 6.6, 1.8 Hz, 2H),
4.25–4.18 (m, 2H), 3.79 (s, 3H), 3.54 (td, J = 11.0, 2.6 Hz, 1H),
2.44–2.20 (m, 4H). 13C NMR (100 MHz, CDCl3) δ 159.0, 134.8,
132.1, 127.2, 119.8, 113.8, 75.4, 66.5, 55.3, 37.6, 22.9.
1
T. Oriyama, A. Ishiwata, T. Sano, T. Matsuda, M.
Takahashi, and G. Koga, Tetrahedron Lett., 36, 5581 (1995).
2
Markó et al. reported that none of the tetrahydrofuran was
formed by the silyl-modified Sakurai reaction of the silane 2 with
aldehydes but the exo-methylenetetrahydropyran was obtained: I.
E. Markó and D. J. Bayston, Tetrahedron Lett., 34, 6595 (1993).
3
A. Mekhalfia, I. E. Markó, and H. Adams, Tetrahedron
Lett., 32, 4783 (1991).
4
Trimethyl{2-[2-(trimethylsiloxy)ethyl]allyl}silane was ob-
tained in 65% yield from 3-methyl-3-buten-1-ol: B. M. Trost, D.
M. T. Chan, and T. N. Nanninga, Org. Synth., 62, 58 (1984).
6
Markó et al. also reported that the TMSOTf-catalyzed con-
densation of reagent 4 with carbonyl compounds could give the
exocyclic isomers selectively by using excess amounts of alkoxy-
trimethylsilane, such as C2H5OTMS: I. E. Markó and A.
Mekhalfia, Tetrahedron Lett., 33, 1799 (1992). I. E. Markó, A.
Mekhalfia, D. J. Bayston, and H. Adams, J. Org. Chem., 57, 2211
(1992).
5
Typical experimental procedure is as follows: To a suspen-
sion of anhydrous tin(II) trifluoromethanesulfonate (5.2 mg, 0.012
mmol) and p-anisaldehyde dimethyl acetal (44.5 mg, 0.24 mmol)
in dichloromethane (2.0 ml) were added trimethyl{2-[2-(trimethyl-
siloxy)ethyl]allyl}silane (68.4 mg, 0.30 mmol) in dichloromethane
(1.5 ml) at –78 °C under an argon atmosphere. The reaction mix-