A new strategy for construction of eight-membered carbocycles by Brook rearrangement mediated [6 + 2] annulation

Article abstract of DOI:10.1021/ol0353767

(Matrix presented) A newly developed strategy for construction of eight-membered carbocycles via [6 + 2] annulation that involves the combination of β-alkenoyl acylsilanes and a vinyllithium derivative is described. A unique feature of this annulative approach is that it enables in one operation and a stereoselective manner construction of eight-membered ring systems containing useful functionalities for further synthetic elaboration from readily available six- and two-carbon components.

Full text of DOI:10.1021/ol0353767

ORGANIC
LETTERS
2003
Vol. 5, No. 20
3705-3707
A New Strategy for Construction of
Eight-Membered Carbocycles by Brook
Rearrangement Mediated [6
Annulation
+ 2]
Kei Takeda,*,†,‡ Hidekazu Haraguchi,† and Yasushi Okamoto‡
Department of Synthetic Organic Chemistry, Graduate School of Medical Sciences,
Hiroshima UniVersity, 1-2-3 Kasumi, Minami-Ku, Hiroshima 734-8551, Japan, and
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical UniVersity,
2630 Sugitani, Toyama 930-0139, Japan
takedak@hiroshima-u.ac.jp
Received July 23, 2003
ABSTRACT
A newly developed strategy for construction of eight-membered carbocycles via [6
+ 2] annulation that involves the combination of â-alkenoyl
acylsilanes and a vinyllithium derivative is described. A unique feature of this annulative approach is that it enables in one operation and a
stereoselective manner construction of eight-membered ring systems containing useful functionalities for further synthetic elaboration from
readily available six- and two-carbon components.
The construction of eight-membered carbocycles remains a
significant synthetic challenge because they constitute com-
mon structural cores of a large number of biologically
important natural and nonnatural products.1 Recently, we
reported a novel and efficient method for constructing seven-2
and eight-membered carbocycles3 using Brook rearrangement
mediated [3 + 4] annulation. In this letter, we describe our
preliminary results for formation of eight-membered car-
bocycles by the unprecedented [6 + 2] annulation. Our basic
strategy, shown in Scheme 1, is the formation of an eight-
Scheme 1
† Hiroshima University.
‡ Toyama Medical and Pharmaceutical University.
(1) (a) Mehta, G.; Singh, V. Chem. ReV. 1999, 99, 881-930. (b)
Molander, G. A. Acc. Chem. Res. 1998, 31, 603-609. (c) Sieburth, S. McN.;
Cunard, N. T. Tetrahedron 1996, 52, 6251-6282. (d) Petasis, N. A.; Patane,
M. A. Tetrahedron 1992, 48, 5757-5821.
(2) (a) Takeda, K.; Takeda, M.; Nakajima, A.; Yoshii, E. J. Am. Chem.
Soc. 1995, 117, 6400-6401. (b) Takeda, K.; Nakajima, A.; Yoshii, E. Synlett
1996, 753-754. (c) Takeda, K.; Nakane, D.; Takeda, M. Org. Lett. 2000,
2, 1903-1905. (d) Takeda, K.; Nakajima, A.; Takeda, M.; Okamoto, Y.;
Sato, T.; Yoshii, E.; Koizumi, T.; Shiro, M. J. Am. Chem. Soc. 1998, 120,
4947-4959. (e) Takeda, K.; Nakajima, A.; Takeda, M.; Yoshii, E.; Zhang,
J.; Boeckman, R. K., Jr. Org. Synth. 1999, 76, 199-213. (f) Takeda, K.;
Ohtani, Y. Org. Lett. 1999, 1, 677-679.
membered ring by oxyanion-accelerated Cope rearrangement4
(2 f 1) of 1,2-divinyl cyclobutanolate, which can be
generated by a tandem sequence involving an internal
(3) Takeda, K.; Sawada, Y.; Sumi K. Org. Lett. 2002, 4, 1031-1033.
10.1021/ol0353767 CCC: $25.00
© 2003 American Chemical Society
Published on Web 09/03/2003

carbonyl attack by the siloxy carbanion (3 f 2) and Brook
rearrangment5 (4 f 3) from â-alkenoyl acylsilane 6 and
vinyllithium derivative 5.
The 1,2-cis stereochemistry, indicated by the presence of
cross-peaks between a proton on the phenyl group and a
methyne proton of the isopropyl group in NOESY experi-
ments, is interpreted as the result of the internally O-Si
coordinated structure 15.7 The generality of this tandem
process has been demonstrated by the formation of five- to
seven-membered carbocycles, although the yield decreased
with increase in ring sizes.8 This trend regarding yield and
ring sizes is in sharp contrast to the corresponding tandem
Brook rearrangement/intramolecular Michael reaction,9 in
which similar yields were obtained with four- to six-
membered carbocylces. The fact that the best yield (86%
total yield) was obtained with a four-membered ring can be
explained by invoking an attractive interaction between the
silyl group and carbonyl oxygen in the six-membered
transition state 16 and/or by assuming a reactantlike structure
for an early transition state originating from the unstable
siloxy carbanion. Encouraged by the above results, we
Since the formation of eight-membered carbocycles using
the oxyanion-accelerated Cope rearrangement of 1,2-divin-
ylcyclobutanes has been well-documented,4 it seemed to us
that the formation of a four-membered ring by the internal
carbonyl attack by the siloxy carbanion (3 f 2) seemed to
be the key element for realization of the above process. First,
we decided to carry out a model experiment on the reaction
of γ-keto acylsilane 11a, which was prepared by a route
starting from 1,3-dithiane derivative 76 as shown in Scheme
2, with phenyllithium to test the feasibility of this approach.
Scheme 2
Scheme 3
When 11a in THF was treated with phenyllithium at -80
°C and allowed to warm to -30 °C, cis-1,2-cyclobutanediol
derivative 12a, Brook rearrangement/cyclization product of
the adduct, was obtained in 67% yield along with silyl-
rearranged products of 12a, 13a (10%), and its dehydration
product 14a (9%). The structural assignment of 12a was
based on the appearance and disappearance of the 13C NMR
signals at δ 82.7 and 83.0 for the quaternary carbons and at
δ 213.4 and 245.0 for the carbonyl carbons, respectively.
proceeded to investigate the possibility of formation of eight-
membered carbocycles by [6 + 2] annulation. The requisite
six-carbon unit 20 was prepared by the route shown in
Scheme 4, which involves addition of cyanohydrins 1710 to
acryloylsilane 1811 followed by hydrolysis of the cyanohydrin
moiety into ketone.
When â-alkenoylsilanes 20 in THF were treated with
â-(trimethylsilyl)vinyllithium 21, generated from â-(tri-
methylsilyl)vinyl bromide with tert-butyllithium, and then
allowed to warm to -10 °C, the desired eight-membered
carbocycles 22 were obtained as a single diasteromer in
acceptable yields and as the only identifiable product.12 The
(4) (a) Paquette, L. A. Tetrahedron 1997, 53, 13971-14020. (b) Wilson,
S. R. Org. React. 1993, 43, 93-250. (c) Bronson, J. J.; Danheiser, R. L. In
ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon: Oxford, 1991; Vol. 5, pp 999-1036. (d) Hill, R. K. In
ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon: Oxford, 1991; Vol. 5, pp 785-826. (e) Paquette, L. A. Angew.
Chem., Int. Ed. Engl. 1990, 29, 609-626. Also, see: (f) Gadwood, R. C.;
Lett, R. M. J. Org. Chem. 1982, 47, 2268-2275.
(5) For reviews on the Brook rearrangement, see: (a) Brook, M. A.
Silicon in Organic, Organometallic, and Polymer Chemistry; John Wiley
& Sons: New York, 2000. (b) Brook, A. G.; Bassindale, A. R. In
Rearrangements in Ground and Excited States; de Mayo, P., Ed.; Academic
Press: New York, 1980; pp 149-221. (c) Brook, A. G. Acc. Chem. Res.
1974, 7, 77-84. For the use of the Brook rearrangement in tandem bond
formation strategies, see: (d) Moser, W. H. Tetrahedron 2001, 57, 2065-
2084. Also, see: (e) Ricci, A.; Degl’Innocenti, A. Synthesis 1989, 647-
660. (f) Bulman Page, P. C.; Klair, S. S.; Rosenthal, S. Chem. Soc. ReV.
1990, 19, 147-195. (g) Qi, H.; Curran, D. P. In ComprehensiVe Organic
Functional Group Transformations; Katritzky, A. R., Meth-Cohn, O., Rees,
C. W., Moody, C. J., Eds.; Pergamon: Oxford, 1995; pp 409-431. (h)
Cirillo, P. F.; Panek, J. S. Org. Prep. Proc. Int. 1992, 24, 553-582. (i)
Patrocinio, A. F.; Moran, P. J. S. J. Braz. Chem. Soc. 2001, 12, 7-31.
(6) Scheller, M. E.; Frei, B. HelV. Chim. Acta 1984, 67, 1734-1747.
(7) For intramolecular chelation involving pentacoordinate silicon spe-
cies: (a) see ref 2d. (b) Takeda, K.; Yamawaki, K.; Hatakeyama, N. J.
Org. Chem. 2002, 67, 1786-1794. (c) Takeda, K.; Nakatani, J.; Nakamura,
H.; Sako, K.; Yoshii, E.; Yamaguchi, K. Synlett 1993, 841-843.
(8) In the reactions of 11b-d, 12b-d were the only identifiable products.
(9) Takeda, K.; Tanaka, T. Synlett 1999, 705-708.
(10) Jacobson, R. M.; Lahm, G. P.; Clader, J. W. J. Org. Chem. 1980,
45, 395-405.
(11) Reich, H. J.; Kelly, M. J.; Olson, R. E.; Holtan, R. C. Tetrahedron
1983, 39, 949-960.
3706
Org. Lett., Vol. 5, No. 20, 2003

enol silyl ether moiety, and of comparison of their spectral
data with those of the corresponding seven-membered
carbocycles.2 The relative stereochemistry was assigned on
the basis of J6,7 (3.6 Hz) and of the presence of cross-peaks
between H-6 and H-7 protons in NOESY experiments.
The selective addition of vinyllithium to the acylsilane
moiety in the presence of ketones observed in both reactions
with 11 and 20 can be attributed to the less encumbered
nature of acylsilanes arising from the abnormally long
Si-CO bond relative to the analogous bond length in
C-CO.13
Scheme 4
In conclusion, we have developed a novel strategy for the
construction of functionalized eight-membered carbocycles
in a stereodefined manner featuring a Brook rearrangement
mediated tandem process. Further expansion and applications
of this methodology are in progress and will be reported in
a forthcoming paper.
1
structure of 22a was assigned on the basis of 13C and H
NMR spectra, which show the carbonyl signal at δ 214.7
and a proton signal at δ 4.64 (d, J ) 11.5 Hz, H-5) and
carbon signals at δ 102.7 and 153.4 corresponding to the
Acknowledgment. Acknowledgment is made to a grant-
in-aid for Scientific Research from the Japanese Ministry of
Education, Sciences, Sports and Culture, the Uehara Memo-
rial Foundation, and the Naito Foundation for partial support
of this research.
Scheme 5
Supporting Information Available: Full experimental
details and characterization data for all new compounds
described. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL0353767
(12) For conversion of the γ-silyl enol silyl ethers into enones, see ref
2d.
(13) Chich, P. C.; Trotter, J. J. Chem. Soc. A 1969, 1778-1783.
Org. Lett., Vol. 5, No. 20, 2003
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