Preparation of a cycloheptane ring from a 1,2-diketone with high stereoselectivity

Article abstract of DOI:10.1021/ol102237b

Treatment of 1,6-dialkylhexa-1,5-diene-3,4-diones with bis(iodozincio) methane gave zinc alkoxides of cis-5,6-dialkylcyclohepta-3,7-diene-1,3-diol in good yields at room temperature. The reaction proceeded with high stereospecificity. Bis(iodozincio)metha

Full text of DOI:10.1021/ol102237b

ORGANIC
LETTERS
2010
Vol. 12, No. 22
5204-5205
Preparation of a Cycloheptane Ring
from a 1,2-Diketone with High
Stereoselectivity
Yoshiaki Takada, Kenichi Nomura, and Seijiro Matsubara*
Department of Material Chemistry, Graduate School of Engineering, Kyoto UniVersity,
Kyoudai-Katsura, Nishikyo, Kyoto 615-8510, Japan
matsubar@orgrxn.mbox.media.kyoto-u.ac.jp
Received September 18, 2010
ABSTRACT
Treatment of 1,6-dialkylhexa-1,5-diene-3,4-diones with bis(iodozincio)methane gave zinc alkoxides of cis-5,6-dialkylcyclohepta-3,7-diene-1,3-
diol in good yields at room temperature. The reaction proceeded with high stereospecificity. Bis(iodozincio)methane converted the diketone
into the cis-divinylcyclopropane-1,2-diol stereoselectively; this diol transformed into the corresponding cycloheptane derivative stereospecifically
via Cope rearrangement.
The Cope rearrangement of cis-divinylcyclopropane has been
recognized as an efficient route to obtain a cycloheptane
skeleton.1,2 Despite its efficiency, the difficulty of the selective
preparation of the cis-isomer of the substrate often causes
the transformation to be less successful. Although some
practical methods for the preparation of the cis-isomer have
been shown,3 most methods yielded the trans-isomers that
require a temperature of over 100 °C to perform the Cope
rearrangement.4 During the course of our research concerning
bis(iodozincio)methane (1), we found the nucleophilic cyclo-
propanation of 1,2-diketone, which gave cis-cyclopropane-1,2-
diol stereoselectively.5 The selectivity was rationalized by a
computational method based on the face-to-face coordination
of 1 with the diketone.6 When the 1,6-dialkylhexa-1,5-diene-
3,4-diones 2 were treated with 1, the products would be zinc
alkoxides of cis-divinylcyclopropane-1,2-diols 3. The alkoxides
of cis-divinylcyclopropane derivatives 3 would undergo Cope
rearrangement more rapidly due to acceleration by the alkoxide
groups (Scheme 1).7 These two reactions can be performed
sequentially without isolation.
A simple treatment of (1E,5E)-1,6-diphenylhexa-1,5-diene-
3,4-dione (2a) at 0 °C with bis(iodozincio)methane (1) gave a
messy mixture. As the Cope-rearrangement product is a zinc
(4) (a) Wender, P. A.; Filosa, M. P. J. Org. Chem. 1976, 41, 3490. (b)
Thomas, E.; Kasatkin, A. N.; Whitby, R. J. Tetrahedron Lett. 2006, 41,
9181. (c) Wallock, N. J.; Donaldson, W. A. Org. Lett. 2005, 7, 2047. (d)
Davies, H. M. L.; Clark, T. J.; Smith, H. D. J. Org. Chem. 1991, 56, 3817.
(e) Davies, H. M.; Doan, D. B. J. Org. Chem. 1999, 64, 8501. (f) Baldwin,
J. E.; Gilbert, K. E. J. Am. Chem. Soc. 1976, 98, 8283.
(5) Ukai, K.; Oshima, K.; Matsubara, S. J. Am. Chem. Soc. 2000, 122
(48), 12047.
(1) (a) Davies, H. M. L. Tetrahedron 1993, 49, 5203. (b) Foley, D. A.;
Maguire, A. R. Tetrahedron 2010, 66, 1131
.
(2) (a) Molandar, G, A. Acc. Chem. Res. 1998, 31, 603. (b) Ni, Y.;
Montgomery, J. J. Am. Chem. Soc. 2004, 126, 11162
.
(3) (a) Lebel, H.; Marcoux, J. F.; Molinaro, C.; Charette, A. B. Chem.
ReV. 2003, 103, 977. (b) Takeda, K.; Takeda, M.; Nakajima, A.; Yoshii, E.
J. Am. Chem. Soc. 1995, 117, 6400. (c) Vuligonda, V.; Garst, M. E.;
Chandraratna, R. A. S. Bioorg. Med. Chem. Lett. 1999, 9, 589. (d) Wallock,
N. J.; Donaldson, W. A. Org. Lett. 2005, 7, 2047. (e) Pantke-Bdcker., A.;
Pohnert, G.; Fischer-Lui, I.; Boland, W. Tetrahedron 1991, 51, 7921. (f)
Olson, J. P.; Davies, H. M. L. Org. Lett. 2008, 10, 573.
(6) Matsubara, S.; Ukai, K.; Fushimi, H.; Yokota, Y.; Yoshino, H.;
Oshima, K.; Omoto, K.; Ogawa, A.; Hioki, Y.; Fujimoto, H. Tetrahedron
2002, 58, 8255.
(7) Evans, D. A.; Golob, A. M. J. Am. Chem. Soc. 1975, 97, 4765.
10.1021/ol102237b  2010 American Chemical Society
Published on Web 10/22/2010

Scheme 1
.
Syntheses of Cycloheptane Derivatives
Table 1. Various Examples of Preparation of
Cycloheptane-1,3-dionesa
2
5 (yield %)b c
,
entry
R1
R2
R3
1
2a
2b
2c
2d
2e
2f
Ph
Ph
H
5a (84%)
5b (93%)
5c (98%)
5d (47%)
5e (41%)
5f (78%)
5g (96%)
5h (99%)
5i (65%)
5j (88%)
5k (86%)
2
p-Tol
p-Tol
H
3
p-Anisyl
4-F-C6H4
1-Naphtyl
2-Furyl
4-t-Bu-C6H4
Me
p-Anisyl
4-F-C6H4
1-Naphtyl
2-Furyl
4-t-Bu-C6H4
Me
H
4
H
enolate 4 which may attack nucleophilically the substrate 2,
the first reaction, that is, the cyclopropanation of 2 with 1, should
complete before the start of the Cope rearrangement to prevent
the side reactions. To realize this situation, we treated the
diketone 2 with 1 at a low temperature for an appropriate period
until the completion of cyclopropanation, and the resulting
mixture was warmed to promote the Cope rearrangement.
Actually, as shown in Scheme 2 (eq 1), (1E,5E)-1,6-diphenyl-
5
H
6
H
7
2g
2h
2i
H
8
H
9
Me
H
Me
H
10
11
2j
2k
Me
Ph
Me
Me
Me
a The reaction was performed with the following scale: 1 (1.2 mmol,
0.35 M THF solution), 2 (1.0 mmol in 5 mL of THF). After 3 h at -78 °C,
10 mL of THF (25 °C) was added in one portion. b Isolated yields. c The
diastereomer was not detected.
anhydride. As shown in Scheme 3, after treatment of 2h with
bis(iodozincio)methane (1) at -78 °C for 3 h and at 25 °C
Scheme 2. Preparation of
(5R,6S)-5,6-Diphenylcycloheptane-1,3-dione
Scheme 3. Trapping of Intermediary Zinc Enolates with
Chlorotrimethylsilane and Acetic Anhydride
for 1 h after an addition of THF, chlorotrimethylsilane was
added. The corresponding silyl enol ether 6 was isolated in
96% yield. Acetylation also worked efficiently to give the
corresponding enol acetate 7 in 82% yield.
Thus, we can show an efficient and facile route to
cyclopropane-1,3-dione derivative 5 starting from 2. The
preparation of 1,2-diketone 2 was accomplished easily by
the reported procedures.9 The further transformations of enol
derivatives 6 and 7 would give the more substituted cyclo-
heptane derivatives with high stereoselectivities.
hexa-1,5-diene-3,4-dione (2a) was treated with 1 for 3 h at -78
°C, and the resulting mixture was warmed to 25 °C gradually
to give the seven-membered ring 5a in 78% yield.8 Moreover,
a dilution procedure improved the yield of 5a up to 84% as
shown in Scheme 2 (eq 2). As the rearrangement is an
intramolecular reaction, the dilution did not affect the reaction
rate and would suppress the side reactions which proceed
intermolecularly.
Some examples of the preparation of cycloheptane-1,3-
diones are shown in Table 1. Various cycloheptane-1,3-
diones substituted with two aryl groups in cis-manner 5 were
prepared and isolated in good yields (Table 1, entries 1-7).
As substituents (R1, R2, R3), an alkyl group did not disturb
the reaction (Table 1, entries 8-11). These transformations
were stereospecific. As shown in entries 8 and 9, the cis-
and trans-isomers were obtained specifically depending on
the E,Z-configuration of the substrate.
Acknowledgment. This work was supported financially
by the Japanese Ministry of Education, Culture, Sports,
Science and Technology.
Supporting Information Available: Experimental pro-
cedures including spectroscopic and analytical data. This
material is available free of charge via the Internet at
http://pubs.acs.org.
The intermediary zinc enolate corresponding to 4 in
Scheme 1 was trapped with chlorotrimethylsilane and acetic
OL102237B
(9) (a) Wehmeier, M.; Wagner, M.; Mu¨llen, K. Chem.sEur. J. 2001,
7, 2197. (b) Mueller-Westerhoff, U. T.; Zhou, M. Tetrahedron Lett. 1993,
34, 571. (c) Constable, E. C.; Harverson, P.; Smith, D. R.; Whall, L. A.
Tetrahedron 1994, 50, 7799.
(8) The structure of 5a was determined by a single-crystal X-ray analysis
(see Supporting Information). The structure of the other products was
detemined by analogy of the structure of 5a.
Org. Lett., Vol. 12, No. 22, 2010
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