Palladium-catalyzed formal cycloaddition of silacyclobutanes with enones: Synthesis of eight-membered cyclic silyl enolates

Article abstract of DOI:10.1021/ol800603z

(Chemical Equation Presented) Treatment of silacyclobutanes with enones under palladium catalysis resulted in formal cycloaddition to yield the corresponding eight-membered ring. The reaction provides a facile and convergent access to synthetically useful eight-membered cyclic silyl enolates.

Full text of DOI:10.1021/ol800603z

ORGANIC
LETTERS
2008
Vol. 10, No. 11
2199-2201
Palladium-Catalyzed Formal
Cycloaddition of Silacyclobutanes with
Enones: Synthesis of Eight-Membered
Cyclic Silyl Enolates
Koji Hirano, Hideki Yorimitsu,* and Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto UniVersity,
Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
oshima@orgrxn.mbox.media.kyoto-u.ac.jp; yori@orgrxn.mbox.media.kyoto-u.ac.jp
Received March 15, 2008
ABSTRACT
Treatment of silacyclobutanes with enones under palladium catalysis resulted in formal cycloaddition to yield the corresponding eight-membered
ring. The reaction provides a facile and convergent access to synthetically useful eight-membered cyclic silyl enolates.
Metal-mediated cycloaddition reactions provide powerful and
convergent approaches to cyclic skeletons from relatively
simple organic molecules.1 Among them, the cycloaddition
of two four-atom fragments ranks as the most attractive route
to eight-membered ring systems.2 Wender has developed
nickel-catalyzed intramolecular cycloaddition of bis(1,3-
diene)s and realized efficient construction of eight-membered
carbocycles.3 On the other hand, the intermolecular variants
have still been challenging. Although highly selective
dimerization reactions of 1,3-dienes have been well estab-
lished,4 only a few examples of intermolecular cross cy-
cloaddition of two different four-atom components have been
reported to date5 except for the photochemical processes.2
During our studies on metal-catalyzed reactions of silacy-
clobutanes, we have found palladium- and nickel-catalyzed
formal intermolecular cycloaddition of silacyclobutanes with
alkynes and aldehydes providing the corresponding six-
membered rings.6,7 In this communication, we report fully
intermolecular palladium-catalyzed formal cycloaddition of
silacyclobutanes with enones leading to eight-membered
rings,8 synthetically useful silyl enolates.9
Treatment of 1,1-dimethylsilacyclobutane (1a) with 1-phen-
yl-2-hexen-1-one (2a) in the presence of 7.5 mol % of
Pd(OAc)2 and 15 mol % of P(c-C6H11)3 in refluxing THF
(5) (a) Carbonaro, A.; Cambisi, F.; Dall’Asta, G. J. Org. Chem. 1971,
36, 1443–1445. (b) Baldenius, K.-U.; tom Dieck, H.; Ko¨nig, W. A.; Icheln,
D.; Runge, T. Angew. Chem., Int. Ed. Engl. 1992, 31, 305–307. (c) Lautens,
M.; Tam, W.; Lautens, J. C.; Edwards, L. G.; Crudden, C. M.; Smith, A. C.
J. Am. Chem. Soc. 1995, 117, 6863–6879.
(1) (a) Lautens, M.; Klute, W.; Tam, W. Chem. ReV. 1996, 96, 49–92.
(b) Fru¨hauf, H.-W. Chem. ReV. 1997, 97, 523–596. (c) Kotha, S.;
Brahmachary, E.; Lahiri, K. Eur. J. Org. Chem. 2005, 4741-4767.
(2) Sieburth, S. M.; Cunard, N. T. Tetrahedron 1996, 52, 6251–6282.
(3) (a) Wender, P. A.; Ihle, N. C. J. Am. Chem. Soc. 1986, 108, 4678–
4679. (b) Wender, P. A.; Ihle, N. C.; Correia, C. R. D. J. Am. Chem. Soc.
1988, 110, 5904–5906. (c) Wender, P. A.; Croatt, M. P.; Witulski, B.
Tetrahedron 2006, 62, 7505–7511.
(6) (a) Takeyama, Y.; Nozaki, K.; Matsumoto, K.; Oshima, K.; Utimoto,
K. Bull. Chem. Soc. Jpn. 1991, 64, 1461–1466. (b) Hirano, K.; Yorimitsu,
H.; Oshima, K Org. Lett. 2006, 8, 483–485. Also see: (c) Hirano, K.;
Yorimitsu, H.; Oshima, K. J. Am. Chem. Soc. 2007, 129, 6094–6095
.
(4) (a) Keim, W.; Behr, A.; Ro¨per, M. In ComprehensiVe Organometallic
Chemistry; Wilkinson, G., Stone, F. G. A., Abel, E. W., Ed.; Pergamon:
New York, 1982; Vol. 8; pp 371-462. (b) Tenaglia, A.; Brum, P.; Waegell,
B. J. Organomet. Chem. 1985, 285, 343–357. (c) Murakami, M.; Itami,
K.; Ito, Y. Synlett 1999, 951-953.
(7) Other groups have also focused on the synthesis of six-membered
rings through metal-mediated formal cycloaddition of silacyclobutanes. (a)
Sakurai, H.; Imai, T. Chem. Lett. 1975, 891-894. (b) Agenet, N.; Mirebeau,
J.-H.; Petit, M.; Thouvenot, R.; Gandon, V.; Malacria, M.; Aubert, C.
Organometallics 2007, 26, 819–830
.
10.1021/ol800603z CCC: $40.75
Published on Web 05/06/2008
2008 American Chemical Society

afforded cycloadduct 3a in 80% yield with a trace amount
(less than 3%) of the ring opening product 4a (Table 1, entry
was converted to 3n in low yield (entry 14). It is noteworthy
that the benzyl ether and terminal olefin moieties were
compatible under the reaction conditions (entries 15 and 16).
However, the reaction with chalcone (2q) resulted in no
formation of the cycloadduct 3q, and two different kinds of
the ring-opening products 4q and 4q′ were obtained (entry
17).
Table 1. Formal Cycloaddition of Silacyclobutane 1a with
Enonesa
Based on the results of Table 1, we are tempted to assume
the reaction mechanism for the formal cycloaddition of the
silacyclobutane 1a with enones 2 as follows (Scheme 1).
entry
2
3, yield (%)b
Scheme 1
1
2a (R1 ) n-Pr, R2 ) Ph)
3a, 80
3b, 67
3c, 89
3d, trace
3e, 82
2c
3c
4
2b (R1 ) n-Pr, R2 ) 4-MeC6H4)
2c (R1 ) n-Pr, R2 ) 4-PhC6H4)
2d (R1 ) n-Pr, R2 ) 4-MeOC6H4)
2e (R1 ) n-Pr, R2 ) 4-FC6H4)
2f (R1 ) n-Pr, R2 ) 4-CF3C6H4)
2g (R1 ) n-Pr, R2 ) 4-MeOCOC6H4)
2h (R1 ) n-Pr, R2 ) 2-Naphthyl)
2i (R1 ) n-Pr, R2 ) 2-Furyl)
2j (R1 ) n-Pr, R2 ) 2-Thienyl)
2k (R1 ) n-Pr, R2 ) 3-Pyridyl)
2l (R1 ) Me, R2 ) Ph)
5
6d
7
3f, 90
3g, 53 (68)e
3h, 78
3i, 76
8
9
10
11
12d
13
14
15
16
17
3j, 62
3k, 44f
3l, 75
2m (R1 ) Ph(CH2)2, R2 ) Ph)
2n (R1 ) i-Pr, R2 ) Ph)
2o (R1 ) CH2dCH(CH2)8, R2 ) Ph)
2p (R1 ) PhCH2O(CH2)9, R2 ) Ph)
2q (R1 ) Ph, R2 ) Ph)
3m, (79)g
3n, (32)
3o, 64
3p, 76
3q, 0h
a A mixture of Pd(OAc)2 (0.038 mmol), P(c-C6H11)3 (0.075 mmol), 1a
(1.5 mmol), and 2 (0.50 mmol) was boiled in THF (5.0 mL) for 20-24 h.
b Isolated yields. 1H NMR yields are in parentheses. Unless otherwise noted,
4 was detected in <3% yield in the crude mixture. c Reaction time was
40 h. d In the presence of 5 mol % of Pd(OAc)2 and 10 mol % of
P(c-C6H11)3. e Ring-opening product 4g was detected in 26% yield.
f Ring-opening product 4k was detected in 15% yield. g Contaminated with
7% of 4m. h Two ring-opening products 4q and 4q′ were detected in 60%
and 13% yields, respectively.
Initial oxidative addition of silacyclobutane 1a to zerovalent
palladium species 5 provides palladasilacyclopentane 6.11
Subsequent coordination of enones 2 to 6, in which the olefin
and carbonyl moieties of enones are coordinated to the
palladium and silicon centers, respectively,12 followed by
insertion to the Si-Pd bond of 6 gives nine-membered
palladacycle 7. Strong π back-donation from the palladium
center of 6 to the olefin moiety would increase the electron
(8) Transition-metal-catalyzed formal cycloaddition of 1,2-disilacy-
clobutenes with 1,3-dienes under thermal- or photochemical conditions was
known to give 1,4-disila-2,6-cyclooctadienes. (a) Sakurai, H.; Kobayashi,
T.; Nakadaira, Y. J. Organomet. Chem. 1978, 162, C43–C47. (b) Jzang,
T. T.; Lee, C. Y.; Liu, C. S. Organometallics 1988, 7, 1265–1270. (c) Jzang,
T. T.; Liu, C. S. Organometallics 1988, 7, 1271–1277. (d) Huang, C. Y.;
Liu, C. S. J. Organomet. Chem. 1989, 373, 353–364. (e) Chiang, H.-J.;
Liu, C. S. J. Organomet. Chem. 1992, 438, C9–C12.
1).10 The reaction is a straightforward way to synthesize
eight-membered cyclic silyl enolates. Electron-neutral and
electron-withdrawing groups on the benzene ring were
tolerant toward the reaction (entries 2, 3, 5, and 6) while
electron-donating group suppressed the formation of the
desired product (entry 4). The reaction with 2g also provided
the cycloadduct 3g, leaving the ester functionality untouched,
although the yield was moderate due to the formation of the
ring-opening product 4g (entry 7). Naphthyl-, furyl-, thienyl-,
and pyridyl-substituted enones also participated in the
reaction to give the corresponding cyclic silyl enolates in
moderate to good yields (entries 8-11). The cycloaddition
with enones bearing substituents other than the n-propyl
group at the ꢀ-position was also conducted. Enones having
a smaller methyl and larger phenylethyl group 2l and 2m
smoothly reacted with 1a to furnish the eight-membered rings
3l and 3m in 75% and 79% yields, respectively (entries 12
and 13). Unfortunately, much more sterically demanding 2n
(9) Synthesis of five-membered cyclic silyl enolates via silylene transfer
from silacyclopropane and hydrodisilane to enones was reported. (a) Calad,
S. A.; Woerpel, K. A. J. Am. Chem. Soc. 2005, 127, 2046-2047. (b)
Okamoto, K.; Hayashi, T. Chem. Lett. 2008, 108-109. Unexpected reactions
of enones with the silylene source affording six-membered cyclic silyl
enolates. (c) Okamoto, K.; Hayashi, T. Org. Lett. 2007, 9, 5067–5069.
Tanaka reported palladium-catalyzed coupling reaction of silacyclobutanes
with acid halides in the presence of a suitable base yielding six-membered
cyclic silyl enolates. (d) Tanaka, Y.; Yamashita, H.; Tanaka, M. Organo-
metallics 1996, 15, 1524–1526. (e) Chauhan, B. P. S.; Tanaka, Y.;
Yamashita, H.; Tanaka, M. Chem. Commun. 1996, 1207-1208. (f) Tanaka,
Y.; Yamashita, M. Appl. Organomet. Chem. 2002, 16, 51–54.
(10) Other ligands such as P(t-Bu)3, P(n-Bu)3, and PPh3 were ineffective.
A Ni(cod)2/2P(c-C6H11)3 catalyst system did not catalyze the reaction.
(11) Silacyclobutanes were found to undergo oxidative addition to
platinum, palladium, and cobalt complexes. (a) Yamashita, H.; Tanaka, M.;
Honda, K. J. Am. Chem. Soc. 1995, 117, 8873–8874. (b) Tanaka, Y.;
Yamashita, H.; Shimada, S.; Tanaka, M. Organometallics 1997, 16,
3246–3248, and ref 7b.
2200
Org. Lett., Vol. 10, No. 11, 2008

density of the carbonyl oxygen because a supported ligand
is strongly σ-donating P(c-C6H11)3 and enables the type of
complexation despite that the Lewis acidity of the silicon of
6 would not appear to be very high. In the case of the ꢀ-alkyl-
substituted enones, rapid reductive elimination generally
takes place to afford the cycloadduct 3 along with the starting
zerovalent palladium complex to complete the catalytic cycle.
However, in the reaction with 2q (R1 ) Ph), palladacycle
intermediate 7 is a σ-benzylpalladium so that the isomer-
ization to the more stable π-benzylpalladium 8 preferably
occurs to delay the reductive elimination. Consequently,
ꢀ-hydride elimination proceeds to give palladium hydride 9
and its isomers 10 and 12, which are in equilibrium through
π-allylpalladium intermediate 11, en route to 4q and 4q′.13
With the reaction conditions described above, formal
cycloaddition of benzene-fused silacyclobutane 1b was also
carried out (Scheme 2). The reaction with 2a led to expected
Scheme 3
Scheme 2
followed by oxidation afforded 17 with excellent diastereo-
selectivity. Aldol reactions of 3a with dimethylacetals also
provided the corresponding highly functionalized ketones 18
stereoselectively (see Supporting Information for the stere-
ochemical assignment).
In conclusion, we have found palladium-catalyzed formal
cycloaddition of silacyclobutanes with enones that efficiently
provides eight-membered cyclic silyl enolates of synthetic
value.
benzene-fused eight-membered cyclic product 13a in 46%
yield with contamination by 4% of six-membered cyclic silyl
ether 14a. Interestingly, chalcone (2q), the reaction of which
with 1,1-dimethylsilacyclobutane (1a) did not provide the
cyclic product (Table 1, entry 17), also underwent the formal
cycloaddition, although the product comprised a 1:1 mixture
of the silyl enolate 13q and the silyl ether 14q (see
Supporting Information for the detailed reaction mechanism).
Finally, to establish the synthetic utility of the catalytic
reaction, we attempted to explore the transformation of the
cycloadducts (Scheme 3). Tamao-Fleming oxidation of the
product 3a led to the corresponding alcohol 15 in 86% yield
(eq 1). The overall transformation is regarded as a conjugate
addition of the hydroxypropyl group to enones. Moreover,
the products were silyl enolates so that they took part in
Mukaiyama aldol-type reaction (eqs 2 and 3). The reaction
of 3l with cyclic acetal 16 in the presence of BF3·OEt2
Acknowledgment. This work was supported by Grants-
in-Aid for Scientific Research and Global COE Research
from MEXT, Japan. K.H. acknowledges JSPS for financial
support.
Supporting Information Available: Detailed experimen-
tal procedures and characterization data of compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL800603Z
(12) The reaction of 1,1-diphenylsilacyclobutane resulted in the recovery
of the starting materials. The fact suggests that the coordination of the
carbonyl moiety of enones to the silicon atom of the palladasilacyclopentane
would be crucial for the reaction. The bulky substituents on the silicon
atom would block out the coordination.
(13) The ring-opening byproducts resulting from the reactions with alkyl-
substituted enones would be formed through a similar reaction pathway.
Org. Lett., Vol. 10, No. 11, 2008
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