Iodotrimethylsilane-induced cyclization of 6-alkynal acetals

Article abstract of DOI:10.1055/s-2001-10792

Treatment of 7-phenyl-6-heptynal dimethyl acetal with iodotrimethylsilane afforded 2-(1-iodobenzylidene)cyclohexyl methyl ether via the intramolecular nucleophilic attack of the carbon-carbon triple bond to the oxonium ion generated by the action of iodotrimethylsilane.

Full text of DOI:10.1055/s-2001-10792

LETTER
293
Iodotrimethylsilane-induced Cyclization of 6-Alkynal Acetals
Kazuaki Takami, Hideki Yorimitsu, Hiroshi Shinokubo, Seijiro Matsubara, Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
Fax +81-75-753-4863; E-mail: oshima@fm1.kuic.kyoto-u.ac.jp
Received 29 November 2000
A series of acetals having acetylenic moieties reacted with
iodotrimethylsilane as summarized in the Table. Several
comments are worth noting. (1) 7-Phenyl-6-heptynal di-
alkyl acetals afforded the mixture of stereoisomers (ca. 1/
4). Stereoselectivity was improved when the substrates
prepared by acetalization with unsaturated alcohols were
used. In particular, treatment of bispropargyl acetal 1g
gave 2g as a single isomer. (2) The formation of a cyclo-
pentane ring was less favorable. Furthermore, stereoselec-
tivity was marginal. (3) 7-Phenyl-6-heptynal acetals gave
the better results compared with 6-tridecynal acetals in re-
gard to yield and stereoselectivity. (4) Treatment of 1a
and 1h with iodotriethylsilane, instead of iodotrimethylsi-
lane, afforded the corresponding products in good yield.
However, stereoselectivity was miserable. The reaction of
1a with iododiethylaluminum gave 2a with the same se-
lectivity as the reaction with iodotrimethylsilane. On the
other hand, chlorotrimethylsilane was not effective at all
to give the chlorinated cyclized product. A mixture of 7-
phenyl-6-heptynal and 1a (ca. 1/1) was obtained.
Abstract: Treatment of 7-phenyl-6-heptynal dimethyl acetal with
iodotrimethylsilane afforded 2-(1-iodobenzylidene)cyclohexyl me-
thyl ether via the intramolecular nucleophilic attack of the carbon-
carbon triple bond to the oxonium ion generated by the action of io-
dotrimethylsilane.
Key words: iodotrimethylsilane, cyclization, 6-alkynal acetal, oxo-
nium ion, vinyl iodide
Iodotrimethylsilane is a useful reagent for ether and ester
bonds cleavage utilizing silicon as the hard acid site and
iodine as the soft basic site.1,2 In the last two decades, io-
dotrimethylsilane-mediated carbon-carbon bond forming
reactions have been developed. The Mukaiyama cross-al-
dol reaction of silyl enolates with acetals proceeds under
iodotrimethylsilane catalysis.3 The Hosomi-Sakurai reac-
tion of acetals with allylsilanes is also carried out in the
presence of a catalytic amount of iodotrimethylsilane.4 In
each case, reactive nucleophiles are used and iodotrimeth-
ylsilane simply acts as a Lewis acidic catalyst. Here we
describe the iodotrimethylsilane-mediated cyclization of
6-alkynal acetals. In the present case, the carbon-carbon
triple bond is the nucleophile that attacks the oxonium ion
generated from acetal by the action of iodotrimethylsi-
lane. Iodotrimethylsilane serves as the source of iodine
that is introduced to the product. While the Prins cycliza-
tion induced by TiCl4 in the literature5 involved a 6-endo-
dig mode to provide dihydropyran derivatives, 6-alkynal
acetal underwent 6-exo-dig cyclization to give methyl-
enecyclohexanes.
Table Iodotrimethylsilane-induced Cyclization of Alkynal
Acetals
I
R1
R1
I
R1
R2O
OR2
OR2
OR2
Me3SiI
+
toluene
n
n
–50 °C→10 °C
n
1
2-(E)
2-(Z)
R2
R1
Entry
n
Yield (%)
E/Z
1
An equimolar amount of iodotrimethylsilane was added to
a solution of 7-phenyl-6-heptynal dimethyl acetal6 (1a) in
toluene at 50 °C. Then, the mixture was allowed to warm
to 10 °C over 2 h. Usual workup and silica gel column pu-
rification afforded the cyclized product 2a in 84% yield as
a mixture of stereoisomers (E/Z = 18/82).7
1
2
3
4
5
6
7
1a
1b
1c
1d
1e
1f
84
100
99
18/82
20/80
20/80
14/86
10/90
9/91
1
1
1
1
1
1
1
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
i-Pr
CH2-c-C6H11
CH2CH=CH2
77
75
CH2Ph
74
CH2CH2Ph
CH2C≡CH
1g
41
<1/99
I
Ph
8
9
1h
1i
0
1
66
33/67
25/75
Ph
Me
Me
n-C6H13
n-C6H13
n-C6H13
46
2a-(E)
OMe
OMe
Ph
1j
10
1
1
1
61
34
81
20/80
50/50
38/62
i-Pr
MeO
OMe
Me3SiI
CH2Ph
11
1k
1a
1h
18
..
+
121)
131)
142)
toluene
–50 °C→10 °C
84%
Ph
Me
82
Ph
I
0
1
61
70
39/61
18/82
Ph
Ph
Me
Me
1a
2a-(Z)
1a
1) Iodotriethylsilane was used instead of iodotrimethylsilane.
2) Iododiethylaluminum was used.
Scheme 1
Synlett 2001 No. 2, 293–295 ISSN 0936-5214 © Thieme Stuttgart · New York

294
K. Takami et al.
LETTER
The plausible mechanism is shown in Scheme 2. Iodotri-
methylsilane abstracts the alkoxy moiety to give the oxo-
nium ion 3 and then intramolecular nucleophilic attack by
the acetylenic moiety would occur. The resulting interme-
diary vinyl cation 4 would be trapped by iodide to afford
2 mainly consisting of the Z isomer. The reason for the
high Z selectivity is still unclear. The bulkiness of two
alkoxy groups seems to be unrelated to the selectivity. We
assume that the cyclization step might be so rapid that
both alkoxytrimethylsilane and iodide might stay near the
alkoxy group during the cyclization. The iodide would
immediately approach to the cationic carbon from the
same side of the alkoxy group to form the Z isomer.
Acknowledgement
This work was supported by Grants-in-Aid for Scientific Research
(Nos. 12305058 and 10208208) from the Ministry of Education,
Science, Sports, and Culture, Government of Japan. H. Y. acknow-
ledges JSPS for financial support. We thank Mr. Hirotaka Kitagawa
for NOE experiment.
References and Notes
(1) a) Olah, G. A.; Prakash, G. K. S.; Krishnamurti, R. In
Advances in Silicon Chemistry: Larson, G. L. Ed., JAI Press:
Greenwich, 1991, Vol.1, pp.1-64. b) Hosomi, A.; Miura, K. In
Lewis Acid Reagents: Yamamoto, H. Ed., Oxford University
Press: New York, 1999, Chap. 8.
(2) a) Ho, T. L.; Olah, G. A. Angew. Chem., Int. Ed. Engl. 1976,
15, 774. b) Jung, M. E.; Lyster, M. A. J. Am. Chem. Soc. 1977,
99, 968.
Me3SiOR2
(3) a) Sakurai, H.; Sasaki, K.; Hosomi, A. Bull. Chem. Soc. Jpn.
1983, 56, 3195.
R1
Me3SiI
+ I
R1
OR2
R2O
OR2
(4) a) Sakurai, H.; Sasaki, K.; Hayashi, J.; Hosomi, A. J. Org.
Chem. 1984, 49, 2808. b) Hosomi, A.; Sakata, Y.; Sakurai, H.
Tetrahedron Lett. 1984, 25, 2383. c) Hosomi, A.; Sakata, Y.;
Sakurai, H. Carbohydr. Res. 1987, 171, 223.
(5) Melany, M. L.; Lock, G. A.; Thomspon, D. W. J. Org. Chem.
1985, 50, 3925.
3
n
1
n
R1
Me3SiOR2
+ I
R1
I
(6) The starting material 1a was prepared according to the
following scheme:
OR2
OR2
1) PhC≡CLi
THF, HMPA
1) Me3SiCl, NaI
2) aqueous HI
I
OTHP
O
4
2
n
n
2) p-TsOH, MeOH
3) Dihydropyran
p-TsOH, ether
76%
(Based on Me3SiCl)
Scheme 2
Ph
1) PCC, CH2Cl2
OH
95%
1a
2) HC(OMe)3
p-TsOH, MeOH
The product 2a was subjected to further transformation
(Scheme 3). Treatment of 2a with butyllithium in hexane8
followed by quenching with water afforded 6 quantita-
tively as a single product,9 probably derived from the vi-
nyllithium intermediate 5 stereochemically defined by the
chelation.10 Quenching 5 with iodine gave 2a-(Z)
selectively11 with contamination by 6 (24%). Reaction of
5 with benzaldehyde followed by Jones oxidation treat-
ment provided 8 in 40% overall yield. Compound 8 was
also obtained by the reaction of 5 with benzoyl chloride.
62%
IR (neat): 2932, 1599, 1490, 1460, 1441, 1376, 1365, 1126,
1071, 1050, 952, 914, 754, 690 cm−1; 1H NMR (CDCl3):
= 1.46 1.57 (m, 2H), 1.58 1.70 (m, 4H), 2.42 (t, J = 6.9
Hz, 2H), 3.32 (s, 6H), 4.39 (t, J = 5.4 Hz, 1H), 7.24 7.29 (m,
3H), 7.36 7.41 (m, 2H); 13C NMR (CDCl3): = 19.20, 23.81,
28.44, 31.93, 52.59, 80.74, 89.97, 104.44, 124.05, 127.55,
128.22, 131.59. Found: C, 77.26; H, 8.81%. Calcd. for
C15H20O2: C, 77.55; H, 8.68%.
(7) Experimental Procedure: A 1.0 M solution of
iodotrimethylsilane in hexane (0.80 mmol, 0.80 mL) was
added dropwise to a stirred solution of 1a (0.19 g, 0.80 mmol)
in anhydrous toluene (2.4 mL) at 50 °C under argon. The
resulting mixture was warmed to 10 °C over 2 h. The reaction
was then quenched with saturated NaHCO3 (10 mL) and was
decolorized with saturated Na2S2O3. The mixture was
extracted with hexane (3 10 mL). The combined organic
layer was dried over anhydrous sodium sulfate and was
concentrated in vacuo to furnish yellow oil. The oil was
chromatographed on a silca gel column (hexane/ethyl
acetate = 20/1) to afford 2a (0.22 g, 0.67 mmol, E/Z = 18/82)
in 84% yield as colorless oil: IR (neat): 2928, 2848, 2814,
1459, 1442, 1227, 1143, 1132, 1095, 1066, 1028, 990, 942,
747, 695 cm−1; 1H NMR (CDCl3): = 1.10 1.28 (m, 1H),
1.33 1.67 (m, 3H), 1.69 1.90 (m, 1H), 1.94 2.11 (m,
1.82H), 2.34 (d, J = 12.9 Hz, 0.82H), 2.49 (dt, J = 4.5 Hz, 13.2
Hz, 0.18H), 2.70 (d, J = 13.2 Hz, 0.18H), 3.08 (s, 0.18H 3),
3.39 (s, 0.82 3H), 3.94 (s, 0.18H), 4.47 (s, 0.82H), 7.19
7.26 (m, 3H), 7.28 7.35 (m, 2H); 13C NMR (CDCl3) For
major isomer: = 20.04, 27.72, 27.95, 32.65, 55.36, 84.58,
96.15, 127.72, 128.28, 128.47, 144.14, 145.31. For minor
Ph
I
Ph
Li
Ph
H
OMe
OMe
OMe
H2O
n-BuLi
hexane
6
5
100%
2a (E/Z = 18/82)
I2
PhCHO
Ph
PhCOCl
56%
Ph
Ph
I
Ph
Ph
O
OH
OMe
75%
OMe
OMe
CrO3
acetone
40% (2 steps)
7 (51/49)
2a-(Z) (E/Z =<5/95)
8
Scheme 3
Synlett 2001, No. 2, 293–295 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Iodotrimethylsilane-induced Cyclization of 6-Alkynal Acetals
295
isomer: = 20.22, 27.21, 27.73, 36.34, 55.36, 74.68, 96.96,
127.72, 128.28, 128.48, 143.86, 146.57. Found: C, 51.42; H,
5.20%. Calcd. for C14H17IO: C, 51.24; H, 5.22%.
(10) Treatment of 2i (E/Z = 19/81) with butyllithium followed by
quenching with water furnished the corresponding reduced
product as a mixture of stereoisomers (E/Z = 78/22). The
stereochemical difference in lithiation of vinylic iodide 2a and
2i may be attributed to the mechanism of iodine-lithium
exchange. The vinylic radical intermediate might exist in the
case of 2a, leading to the loss of the starting stereochemistry.
For the mechanistic diversity of halogen-lithium exchange,
see: Bailey, W. F.; Carson, M. W. J. Org. Chem. 1998, 63,
9960 and cited therein.
(8) Shinokubo, H.; Miki, H.; Yokoo, T.; Oshima, K.; Utimoto, K.
Tetrahedron 1995, 51, 11681.
(9) The stereochemistry of 6 was determined by NOE experiment.
Ph
H
12%
H
OMe
(11) The stereochemistry of 2a was determined by combining this
fact with the exclusive formation of 6 in the reaction of 5 with
water.
Article Identifier:
1437-2096,E;2001,0,02,0293,0295,ftx,en;Y19100ST.pdf
Synlett 2001, No. 2, 293–295 ISSN 0936-5214 © Thieme Stuttgart · New York