Fluoride ion-mediated intramolecular aldol cyclization of 7-(t-butyldimethylsiloxy)-7-octenal

Article abstract of DOI:10.1246/cl.2000.932

Polyoxy 8-membered ring compound was synthesized in moderate to good yields by intramolecular aldol cyclization of 7-(t-butyldimethylsiloxy)-7-octenal using tetrabutylammonium fluoride (TBAF).

Full text of DOI:10.1246/cl.2000.932

932
Chemistry Letters 2000
Fluoride Ion-Mediated Intramolecular Aldol Cyclization of 7-(t-Butyldimethylsiloxy)-7-octenal
Iwao Hachiya, Nobutaka Kobayashi, Hiroyuki Kijima, Khanitha Pudhom, and Teruaki Mukaiyama
Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601
(Received May 8, 2000; CL-000439)
Polyoxy 8-membered ring compound was synthesized in
moderate to good yields by intramolecular aldol cyclization of
7-(t-butyldimethylsiloxy)-7-octenal using tetrabutylammonium
fluoride (TBAF).
considered: that is, 1) transformation of an alcohol or an ester
group to the corresponding aldehyde after its ketone part was
converted to silyl enol ether; 2) protection of the aldehyde
group before the silyl enol ether was formed and then to regen-
erate the aldehyde group by deprotection. It was already shown
that transformation of the ketoaldehyde to ω-(α-bromoketo)-
aldehyde via a silyl enol ether proceeded smoothly after protec-
tion of the aldehyde as its O,S-acetal.8,11 Based on these
results, silyl enol ether, a precursor of cyclization, was regio-
selectively formed by treating O,S-acetal with a base and a tri-
alkylsilyl trifluoromethanesulfonate. In this communication,
we would like to report a successful method for the preparation
of 8-membered ring compounds by fluoride ion-mediated
intramolecular aldol cyclization of 7-(t-butyldimethylsiloxy)-7-
octenal under mild conditions.12
O-Trimethylsilyl monothiophenyl acetal 3a was prepared by
treating ketoaldehyde 2a with phenylthiosilane in the presence of
a catalytic amount of trimethylsilyl perchlorate. The acetal 3a
was transformed to the corresponding silyl enol ether 4a by using
lithium hexamethyldisilazide and t-butyldimethylsilyl trifluoro-
methanesulfonate (TBSOTf). Although the deprotection of 4a in
1 M citric acid methanol solution gave the desired aldehyde 5a in
83% yield, it still needed a long reaction time before completing
the deprotection in a large scale experiment. It is probably due to
low solubility of 4a in methanol. The desired deprotection pro-
ceeded to afford 5a in 95% yield when anhydrous TBAF was
used in THF solution at –78 °C for 2 h. The effect of Lewis acids
such as SnCl2, Sn(OTf)2, FeCl3, MgBr2·OEt2, InCl3,
InCl3–TBSCl, TrCl–SnCl2, and ZnI2 was examined in the
intramolecular aldol cyclization of 5a; however, no desired aldol
adducts were obtained and several side reactions such as decom-
position of 5a including deprotection of TBS and PMB groups
took place and a small amount of 5a was recovered. Then, the
synthetic plan was changed to generating a reactive enolate anion
by treating 5a with fluoride ion. When the TBAF-mediated
intramolecular aldol cyclization of 5a was tried in THF at –45 °C
for 1 h, a mixture of 6a-α and 6a-β was obtained together with
6a-β’. Acetylation of these aldol adducts gave 7a-α (6.7%), 7a-β
(33.4%), and 7a-β’ (38.6%), respectively, in two steps from 5a.13
Configurations of 6a-β’ and 7a-β’ were determined by the trans-
formation to the corresponding enone 1.9 This transformation
shows 7a-β’ to be a new diastereomer which had not been
obtained by SmI2-mediated intramolecular aldol reaction.9 Next,
the present method was applied to the synthesis of other 8-
membered ring compound, a precursor of the synthesis of Taxol
derivatives. The aldehydes 5b and 5c were also prepared
according to the procedure depicted in Scheme 2.
Tetrabutylammonium fluoride-mediated intramolecular aldol
reaction of 5b proceeded smoothly to give 6b-α (8%) and 6b-β
(62%). In the case of 5c, a mixture of 6c-α and 6c-β was
obtained in 45% yield.14 Furthermore, the aldehyde 8 also
worked well to afford 9 in 85% yield (eq 1).
Several useful methods are known for the syntheses of
macrocyclic compounds: e.g., conventional macrolactonizations
of the corresponding active ω-hydroxyl carboxylic esters,1 and
carbon–carbon bond forming cyclizations using Heck2 and
Stille3 coupling reactions. Recently, a ring closure by olefin
metathesis using Grubbs’ catalyst is often employed as a pow-
erful method for carbon–carbon bond forming cyclization
because of its applicability to macrocyclic compounds of vari-
ous ring sizes.4 On the other hand, it is well-known that the
intramolecular aldol reactions are convenient tools for the syn-
theses of various cyclic compounds.5 Most of these reactions
were applied to the formations of five or six membered ring
compounds under thermodynamic conditions by using such
bases as alkali hydroxides and so on. Danishefsky demonstrated
a ring closure in the total syntheses of the 16-membered
macrolides, epothilones A and B, by macroaldolizations of
potassium enolates of the corresponding ω-formyl esters having
no α-proton in the aldehyde part under kinetic conditions.6
Further, the usefulness of SmI2-mediated intramolecular
Reformatsky reactions was shown in the syntheses of medium-
membered ring compounds by Yamaguchi and Inanaga.7 In our
total synthesis of Taxol, SmI2-mediated intramolecular aldol
reaction of ω-(α-bromoketo)aldehyde was successfully applied to
the synthesis of a key intermediate 1, polyoxy 8-membered ring
compound corresponding to the B ring of Taxol (Scheme 1).8–10
In the present experiment, the fluoride ion-mediated
intramolecular aldol-type cyclization of 7-(t-butyldimethyl-
siloxy)-7-octenal was investigated in order to develop an alter-
native method for the efficient preparation of the above key
intermediate 1 (Scheme 1). It is known that a silyl enol ether of
a ketone or an ester having an aldehyde group with α-proton in
the same molecule can hardly be prepared because the enolization
of aldehyde part takes place faster than those of ketones and
esters. Then, two possible ways for the preparation of silyl enol
ethers having an enolizable aldehyde in the same molecule were
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
933
This work was partially supported by a Grant-in-Aid for
Scientific Research from Ministry of Education, Science, Sports
and Culture, Japan.
References and Notes
1
2
J. Mulzer, in “Comprehensive Organic Synthesis,” ed. by B. M.
Trost, I. Fleming, and E. Winterfeldt, Pergamon Press, Oxford, U. K.
(1991), Vol. 6, p. 323; G. Rousseau, Tetrahedron, 51, 2777 (1995).
J. Tsuji, “Palladium Reagents and Catalysts. Innovations in Organic
Synthesis,” John Wiley, New York (1995); J. T. Link and L. E.
Overman, in “Metal-catalyzed Cross Coupling Reactions in Organic
Synthesis,” ed. by F. Diederich and P. J. Stang, Wiley–VCH,
Weinheim (1998), Chap. 6, p. 231.
3
T. N. Mittchell, in “Metal-catalyzed Cross Coupling Reactions in
Organic Synthesis,” ed. by F. Diederich and P. J. Stang,
Wiley–VCH, Weinheim (1998), Chap. 4, p. 167.
4
5
See review; R. H. Grubbs and S. Chang, Tetrahedron, 54, 4413
(1998).
C. H. Heathcock, in “Comprehensive Organic Synthesis,” ed. by B.
M. Trost, I. Fleming, and C. H. Heathcock, Pergamon Press, Oxford,
U. K. (1991), Vol. 2, p. 133;
6
A. Balong, D. Meng, T. Kamenecka, P. Bertinato, D.-S. Su, E. J.
Sorensen, and S. J. Danishefsky, Angew. Chem., Int. Ed. Engl., 35,
2801 (1996); D. Meng, P. Bertinato, A. Balong, D.-S. Su, T.
Kamenecka, E. J. Sorensen, and S. J. Danishefsky, J. Am. Chem.
Soc., 119, 10073 (1997). Macroaldolizations of titanium enolate in
the total synthesis of Rapamycin; C. M. Hayward, D. Yohannes, and
S. J. Danishefsky, J. Am. Chem. Soc., 115, 9345 (1993).
T. Tabuchi, K. Kawamura, J. Inanaga, and M. Yamaguchi,
Tetrahedron Lett., 27, 3889 (1986); E. Vedejs and S. Ahmad,
Tetrahedron Lett., 29, 2291 (1988); T. Moriya, Y. Hanada, J.
Inanaga, and M. Yamaguchi, Tetrahedron Lett., 29, 6947 (1988); J.
Inanaga, Y. Yokoyama, Y. Hanada, and M. Yamaguchi, Tetrahedron
Lett., 32, 6371 (1991); M. Inoue, M. Sasaki, and K. Tachibana,
Tetrahedron Lett., 38, 1611 (1997); F. Matsuda, T. Sakai, N. Okada,
and M. Miyashita, Tetrahedron Lett., 39, 863 (1998).
7
8
9
I. Shiina, K. Uoto, N. Mori, T. Kosugi, and T. Mukaiyama, Chem.
Lett., 1995, 181.
T. Mukaiyama, I. Shiina, H. Iwadare, H. Sakoh, Y. Tani, M.
Hasegawa, and K. Saitoh, Proc. Jpn. Acad., 73B, 95 (1997); T.
Mukaiyama, I. Shiina, H. Iwadare, M. Saitoh, T. Nishimura, N.
Ohkawa, H. Sakoh, K. Nishimura, Y. Tani, M. Hasegawa, K.
Yamada, and K. Saitoh, Chem. Eur. J., 5, 121 (1999).
10 For a review of the construction of cyclooctanoid systems, see G.
Mehta and V. Singh, Chem. Rev., 99, 881 (1999).
11 D. A. Evans, L. K. Truesdale, K. G. Grimm, and S. L. Nesbitt, J.
Am. Chem. Soc., 99, 5009 (1977); A. Kusche, R. Hoffmann, I.
Münster, P. Keiner, and R. Brückner, Tetrahedron Lett., 32, 467
(1991).
12 E. Nakamura, M. Shimizu, I. Kuwajima, J. Sakata, K. Yokoyama,
and R. Noyori, J. Org. Chem., 48, 932 (1983).
13 To a solution of 5a (206.7 mg, 0.2660 mmol) in THF (1.3 mL) was
added slowly anhydrous TBAF in THF (0.5 M, 0.54 mL, 0.27 mmol)
at –45 °C and then the mixture was stirred for 1 h. Aqueous saturat-
ed sodium hydrogencarbonate (2 mL) was added to quench the reac-
tion. The mixture was extracted with ethyl acetate (10 mL × 3). The
combined organic layer was washed with water (10 mL) and brine
(10 mL), dried over Na2SO4. The organic solvents were evaporated
under reduced pressure and the crude product was purified by thin-
layer chromatography on silica gel (hexane/ethyl acetate = 5/1) to
afford the mixture of 6a-α and 6a-β (73.1 mg) and 6a-β’ (78.9 mg),
respectively. To a solution of the mixture of 6a-α and 6a-β (73.1
mg) and DMAP (1.3 mg, 0.011 mmol) in pyridine (2.5 mL) was
added acetic anhydride (0.39 mL, 4.10 mmol) at 0 °C and then the
mixture was stirred for 1 h at rt. Phosphate buffer (3 mL, pH = 7)
was added to quench the reaction. The mixture was extracted with
ethyl acetate (10 mL × 3). The combined organic layer was washed
with saturated aqueous copper(II) sulfate (10 mL), saturated aqueous
sodium hydrogencarbonate (10 mL), water (10 mL) and brine (10
mL), dried over Na2SO4. The organic solvents were evaporated
under reduced pressure and the crude product was purified by thin-
layer chromatography on silica gel (hexane/ethyl acetate = 6/1) to
afford 7a-α (12.6 mg, 6.7%), 7a-β (62.7 mg, 33.4%) in two steps
from 5a. 6a-β’ was acetylated according to the above method to
afford 7a- β’ (72.4 mg, 38.6%) in two steps from 5a.
14 No attempts have been made to optimize this reaction.
Configuration assignment was not made.