Gold-catalyzed tandem cyclization of dienol silyl ethers for the preparation of bicyclo[4.3.0]nonane derivatives

Article abstract of DOI:10.1002/anie.201001061

[Figure Presented] Tandem bicycle: A gold-catalyzed geminal carbo-functionalization reaction of 3-siloxy-1,3-dien-8-ynes proceeded smoothly to give bicyclo[4.3.0]nonanes stereoselectively through ring expansion of the bicyclic carbene complex intermediates. The product configuration was different from that of the thermal Diels-Alder adduct.

Full text of DOI:10.1002/anie.201001061

Angewandte
Chemie
DOI: 10.1002/anie.201001061
Cyclization Reactions
Gold-Catalyzed Tandem Cyclization of Dienol Silyl Ethers for the
Preparation of Bicyclo[4.3.0]nonane Derivatives**
Hiroyuki Kusama, Yusuke Karibe, Yuji Onizawa, and Nobuharu Iwasawa*
We previously reported the geminal carbo-functionalization
reaction of alkynes on treatment of 3-siloxy-1,3-dien-7-ynes 1
with [W(CO)6] or [ReCl(CO)5] under photoirradiation to give
bicyclo[3.3.0]octane derivatives 2 in good yield (Scheme 1).[1]
this intermediate is intriguing (Scheme 1). We now report that
1,2-alkyl migration[3] occurred at the generated carbene
moiety to give ring-expanded products by employing 3-
siloxy-1,3-dien-8-yne derivatives as substrates, to stereoselec-
tively obtain synthetically useful bicyclo[4.3.0]nonane deriv-
atives, whose configuration was different from that of the
Diels–Alder adduct.
We first examined the reaction of 3-siloxy-1,3-dien-8-yne
3a with the geometry of the silyl enol ether moiety as (Z)[4] by
using various electrophilic transition-metal catalysts.
Although [W(CO)5(thf)] or [ReCl(CO)5] gave the products
in reasonable yield (45% and 78%, respectively),[5] the
cationic gold catalyst gave the best result. Thus, treatment of
3a with 10 mol% of [AuClPPh3]/AgSbF6[6] in the presence of
molecular sieves (4 ꢀ) gave bicyclo[4.3.0]nonane derivative
4a, a formal [4+2] cycloadduct, as a single stereoisomer in
92% yield (Scheme 2).[7,8] Interestingly, the configuration of
the product was different from that of the thermal Diels–
Alder adduct 5 obtained stereoselectively by heating a
solution of (Z)-3a in toluene for 1.5 h.[9] Thus, two diastereo-
isomers[10] of the same bicyclo[4.3.0]nonane derivative were
obtained selectively by choosing AuI-catalyzed or thermal
conditions.
Scheme 1. Tandem cyclization of dienol silyl ethers.
The reaction was thought to proceed through nucleophilic
attack of the silyl enol ether moiety to the electrophilically
activated alkyne followed by attack of the generated alkenyl
metallic species A to the a,b-unsaturated silyloxonium moiety
at the position b to the metal to give bicyclic carbene complex
intermediate B, which gave the product through 1,2-hydrogen
shift with regeneration of the catalyst.[2] We then thought of
the possibility of carrying out a similar geminal carbo-
functionalization reaction by employing one-carbon-atom
elongated substrates (3-siloxy-1,3-dien-8-ynes 3) with the
expectation that 5-exo attack of the silyl enol ether moiety
followed by ring closure (geminal carbo-functionalization)
would give bicyclo[3.3.0]octane derivative D having a carbene
complex moiety as a substituent on the bridgehead carbon
atom. As there is no a-hydrogen atom at the carbene complex
moiety, 1,2-hydrogen shift is not possible and the behavior of
Next, we examined the reaction of 3-siloxy-1,3-dien-8-yne
derivative 3a with the geometry of the silyl enol ether moiety
as (E)[4] under thermal and AuI-catalyzed conditions
(Scheme 2). In this case, (E)-3a did not undergo thermal
[*] Dr. H. Kusama, Y. Karibe, Dr. Y. Onizawa, Prof. Dr. N. Iwasawa
Department of Chemistry, Tokyo Institute of Technology
2-12-1, O-okayama, Meguro-ku, Tokyo 152-8551 (Japan)
Fax: (+81)3-5734-2931
E-mail: niwasawa@chem.titech.ac.jp
[**] This research was supported in part by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science,
and Technology of Japan. Y.O. was granted a Research Fellowship of
the Japan Society for the Promotion of Science for Young Scientists.
Scheme 2. AuI-catalyzed and thermal cyclization of dienynes 3a.
E=CO2Me; TIPS=triisopropylsilyl; M.S.=molecular sieves; DCE=di-
chloroethane.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201001061.
Angew. Chem. Int. Ed. 2010, 49, 4269 –4272
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4269

Communications
Diels–Alder reaction; however, treatment of (E)-3a with
The stereoselectivity of the reaction could be explained as
follows. Concerning the first cyclization, H was thought to be
more favorable than I because of steric repulsion between the
TIPS group and the phenyl substituent, and the second
cyclization proceeded preferentially via transition state TS-1,
because the phenyl group in another possible transition state
TS-2 is oriented toward the concave position (Scheme 4).[15]
10 mol% AuI catalyst at room temperature afforded a good
yield of the same product as obtained in the AuI-catalyzed
reaction of (Z)-3a.
The proposed mechanism of the reaction is shown at the
bottom of Scheme 2. First, zwitterionic intermediate E was
generated by 5-exo nucleophilic attack of the silyl enol ether
moiety to the electrophilically activated p-alkyne complex.[11]
The alkenyl metallic species underwent intramolecular attack
at the b position of the metal to the a,b-unsaturated silyl
oxonium moiety to generate bicyclic unstable carbene com-
plex F. Finally, the carbene moiety underwent 1,2-alkyl
migration of the benzylic carbon atom, the electron density
of which was higher than the other neighboring methylene
carbon atom, to give the product with regeneration of the
catalyst.
Support for the mechanism of the reaction was obtained
by the following experiments (Scheme 3). Treatment of (Z)-
3a with 25 mol% of [AuClPPh3]/AgSbF6 in the presence of
Scheme 4. Transition states of gold-catalyzed tandem cyclization.
We next examined the generality of this AuI-catalyzed
stereoselective cyclization reaction (Table 1). The substrates 3
with phenyl or alkyl groups for R1 and R3 were cyclized to
afford the corresponding bicyclic enol silyl ethers in good
Table 1: Tandem cyclization of E- or Z-dienynes 3a–i.
Entry
Substrate
R1, R2, R3
X
Product (yield [%])
1
2
3
4
5
6
7
8
9
(E)-3a
(E)-3b
(E)-3c
(Z)-3d
(Z)-3e
Ph, H, Ph
Ph, H, Me
Me, H, Ph
Ph, H, H
Ph, Me, H
Ph, H, Ph
Ph, H, Me
Me, H, Me
Ph, H, Me
C(CO2Me)2
C(CO2Me)2
C(CO2Me)2
CH2
4a (75)
4b (82)
4c (88)
4d (45)
4e (76)
4 f (72)
4g (77)
4h (68)
4i (66)
Scheme 3. Trapping of intermediates. E=CO2Me; Ts=p-toluenesul-
fonyl.
CH2
(E)-3 f[a,b]
(E)-3g[a,c]
(E)-3h[a,c]
(Z)-3i
N Ms
À
À
N Ts
À
N Ts
O
7.5 equivalents of CD3OD gave monocyclic ketone 6,[12] the
hydrolyzed product of the exo-cyclized zwitterionic inter-
mediate E, in which most of the deuterium was observed at
the one side of the alkene. Furthermore, treatment of an
internal alkyne derivative 7 with 10 mol% of cationic AuI
catalyst gave bicyclo[3.3.0]octane derivative 8, geminal carbo-
functionalization product, which was produced by 1,2-hydro-
gen shift at the carbene complex moiety. In addition, although
the type of the metal catalyst is different, treatment of (E)-3h
with 10 mol% [ReCl(CO)5] gave tricyclic compounds 9 and
10, which were produced by insertion of the carbene complex
[a] Reaction temperature was 808C. [b] Ms=methanesulfonyl. [c] Ts=p-
toluenesulfonyl.
yield (Table 1, entries 1–3). Even the reaction of substrates
without the geminal-diester moiety (3d and 3e) also pro-
ceeded to afford the corresponding bicyclic enol silyl ethers
albeit in somewhat lower yields (Table 1, entries 4 and 5). The
substrates containing nitrogen or oxygen atoms in the tether
were also cyclized to afford the corresponding bicyclic enol
silyl ethers in good yield (Table 1, entries 6–9). All these
products were obtained as a single diastereomer, whose
configuration was different from that of the thermal Diels–
Alder reaction.[16]
À
moiety into the neighboring C H bonds in the carbene
complex intermediate related to F.[13,14] These results sup-
ported the proposal that the reaction proceeded through exo-
cyclization and 1,2-alkyl or 1,2-hydrogen shift occurred from
the carbene complex intermediate containing a bicyclo-
[3.3.0]octane skeleton.
Interestingly, when the reaction of internal alkyne 7,
which gave 1,2-hydrogen shift product 8 on treatment with
4270 www.angewandte.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2010, 49, 4269 –4272

Angewandte
Chemie
cationic AuI catalyst, was carried out with 10 mol% of AuCl3/
AgSbF6,[17] 1,2-alkyl migration occurred to give bicyclo-
[4.3.0]nonane derivative 11 in 70% yield (Scheme 5) .[18] It
is thought that, in case of the highly electron-deficient cationic
3519; Angew. Chem. Int. Ed. 2007, 46, 3410 – 3449; b) C.
Bruneau, Angew. Chem. 2005, 117, 2380 – 2386; Angew. Chem.
Int. Ed. 2005, 44, 2328 – 2334; c) E. Jimꢂnez-Nfflæez, A. M.
Echavarren, Chem. Commun. 2007, 333 – 346; d) V. Michelet,
P. Y. Toullec, J.-P. GenÞt, Angew. Chem. 2008, 120, 4338 – 4386;
Angew. Chem. Int. Ed. 2008, 47, 4268 – 4315; e) A. M. Echavar-
ren, C. Nevado, Chem. Soc. Rev. 2004, 33, 431 – 436; f) J. Marco-
Contelles, E. Soriano, Chem. Eur. J. 2007, 13, 1350 – 1357; g) F.
Alonso, I. P. Beletskaya, M. Yus, Chem. Rev. 2004, 104, 3079 –
3159; h) G. Zeni, R. C. Larock, Chem. Rev. 2004, 104, 2285 –
2309; i) M. lvarez-Corral, M. Muæoz-Dorado, I Rodríguez-
García, Chem. Rev. 2008, 108, 3174 – 3198; j) N. T. Patil, Y.
Yamamoto, Chem. Rev. 2008, 108, 3395 – 3442.
[3] For recent reviews of 1,2-alkyl migration of carbene intermedi-
ates, see: B. Crone, S. F. Kirsch, Chem. Eur. J. 2008, 14, 3514 –
3522.
[4] See the Supporting Information for preparative methods.
[5] The reaction of 3a with [W(CO)5(thf)] proceeded to give the
products as a mixture of diastereoisomers (4a 22% + 23%). The
reaction of 3a with [ReCl(CO)5] proceeded to give the products
as a mixture of silyl enol ether 4a and its hydrolyzed product
(9% + 69%).
Scheme 5. 1,2-Hydrogen shift or 1,2-alkyl migration of the carbene
intermediate. E=CO2Me. Conditions: A) 10 mol% [AuClPPh3]/AgSbF6,
4 ꢀ M.S., DCE, 808C, 0.25 h; B) 10 mol% AuCl3/AgSbF6, 4 ꢀ M.S.,
DCE, RT, 0.3 h.
[6] For recent reviews on gold-mediated homogeneous catalysis,
see: a) A. Fꢁrstner, Chem. Soc. Rev. 2009, 38, 3208 – 3221; b) P.
Belmont, E. Parker, Eur. J. Org. Chem. 2009, 6075 – 6089; c) Z.
Li, C. Brouwer, C. He, Chem. Rev. 2008, 108, 3239 – 3265; d) A.
Arcadi, Chem. Rev. 2008, 108, 3266 – 3325; e) E. Jimꢂnez-Nfflæez,
A. M. Echavarren, Chem. Rev. 2008, 108, 3326 – 3350; f) D. J.
Gorin, B. D. Sherry, F. D. Toste, Chem. Rev. 2008, 108, 3351 –
3378; g) J. Muzart, Tetrahedron 2008, 64, 5815 – 5849; h) R.
Skouta, C.-J. Li, Tetrahedron 2008, 64, 4917 – 4938; i) H. C. Shen,
Tetrahedron 2008, 64, 7847 – 7870; j) A. S. K. Hashmi, Chem.
Rev. 2007, 107, 3180 – 3211; k) D. J. Gorin, F. D. Toste, Nature
2007, 446, 395 – 403; l) L. Zhang, J. Sun, S. A. Kozmin, Adv.
Synth. Catal. 2006, 348, 2271 – 2296; m) A. S. K. Hashmi, G. J.
Hutchings, Angew. Chem. 2006, 118, 8064 – 8105; Angew. Chem.
Int. Ed. 2006, 45, 7896 – 7936; n) R. A. Widenhoefer, X. Han,
Eur. J. Org. Chem. 2006, 4555 – 4563.
AuIII carbene complex intermediate, 1,2-alkyl migration is
accelerated by the highly electrophilic character of the
carbene carbon atom, whereas in the moderately electron-
deficient AuI carbene complex, 1,2-hydrogen shift became the
favorable reaction pathway.[19] Thus, two types of product
could be obtained selectively by the appropriate choice of the
AuI or AuIII catalyst.
In summary, we have developed gold-catalyzed geminal
carbo-functionalization of 3-siloxy-1,3-dien-8-ynes 3 to give
bicyclo[4.3.0]nonanes 4 stereoselectively through a ring-
expansion reaction of the bicyclic carbene complex inter-
mediates. The reaction gave synthetically useful bicyclo-
[4.3.0]nonane derivatives 4 whose configuration is different
from that of the thermal Diels–Alder adduct.
[7] AgSbF6 alone failed to catalyze the reaction of 3a. Starting
material 3a was mostly recovered.
[8] For examples of transition-metal-catalyzed [4+2] cycloaddition
of 1,3-dien-8-yne derivatives, see: a) P. A. Wender, T. E. Smith, J.
Org. Chem. 1995, 60, 2962 – 2963; b) R. Shintani, Y. Sannohe, T.
Tsuji, T. Hayashi, Angew. Chem. 2007, 119, 7415 – 7418; Angew.
Chem. Int. Ed. 2007, 46, 7277 – 7280; c) D. Motoda, H. Kinoshita,
H. Shinokubo, K. Oshima, Angew. Chem. 2004, 116, 1896 – 1898;
Angew. Chem. Int. Ed. 2004, 43, 1860 – 1862; d) B. Wang, P. Cao,
X. Zhang, Tetrahedron Lett. 2000, 41, 8041 – 8044; e) S. R.
Gilbertson, G. S. Hoge, D. G. Genov, J. Org. Chem. 1998, 63,
10077 – 10080; f) K. Kumar, R. S. Jolly, Tetrahedron Lett. 1998,
39, 3047 – 3048; g) A. Fꢁrstner, K. Majima, R. Martín, H.
Krause, E. Kattnig, R. Goddard, C. W. Lehmann, J. Am.
Chem. Soc. 2008, 130, 1992 – 2004; h) A. Fꢁrstner, C. C. Stimson,
Angew. Chem. 2007, 119, 9001 – 9005; Angew. Chem. Int. Ed.
2007, 46, 8845 – 8849.
Experimental Section
General procedure: 3-Siloxy-1,3-diene-8-yne (0.1 mmol) in degassed
dichloroethane (1 mL) was added to a mixture of [AuClPPh3]
(0.01 mmol), AgSbF6 (0.01 mmol), and activated 4 ꢀ molecular
sieves (100 mg). After the mixture was stirred for 1 h at room
temperature, the reaction mixture was filtered through a short pad of
silica gel, and the filtrate was concentrated under reduced pressure.
The residue was purified by preparative thin layer chromatography
(PTLC) to give the bicyclic compound.
Received: February 21, 2010
Published online: May 5, 2010
[9] For an example of Diels–Alder reaction of 1,3-dien-8-yne
derivatives, see: T. Stellfeld, U. Bhatt, M. Kalesse, Org. Lett.
2004, 6, 3889 – 3892.
[10] The relative configuration of 4a and 5 was determined by
observation of NOE spectra. For details, see the Supporting
Information.
[11] a) K. Maeyama, N. Iwasawa, J. Am. Chem. Soc. 1998, 120, 1928 –
1929; b) N. Iwasawa, K. Maeyama, H. Kusama, Org. Lett. 2001,
3, 3871 – 3873; c) H. Kusama, H. Yamabe, N. Iwasawa, Org. Lett.
2002, 4, 2569 – 2571; d) N. Iwasawa, T. Miura, K. Kiyota, H.
Kusama, K. Lee, P. H. Lee, Org. Lett. 2002, 4, 4463 – 4466; for
important example, see also: e) S. T. Staben, J. J. Kennedy-
Keywords: alkynes · cycloaddition · gold ·
homogeneous catalysis · ring expansion
.
[1] a) H. Kusama, H. Yamabe, Y. Onizawa, T. Hoshino, N. Iwasawa,
Angew. Chem. 2005, 117, 472 – 474; Angew. Chem. Int. Ed. 2005,
44, 468 – 470; b) Y. Onizawa, H. Kusama, N. Iwasawa, J. Am.
Chem. Soc. 2008, 130, 802 – 803; c) H. Kusama, Y. Onizawa, N.
Iwasawa, J. Am. Chem. Soc. 2006, 128, 16500 – 16501.
[2] For recent reviews of electrophilic activation of alkynes, see:
a) A. Fꢁrstner, P. W. Davies, Angew. Chem. 2007, 119, 3478 –
Angew. Chem. Int. Ed. 2010, 49, 4269 –4272
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
4271

Communications
Smith, D. Huang, B. K. Corkey, R. L. LaLonde, F. D. Toste,
[17] For examples of difference of reactivity between AuI and AuIII
,
Angew. Chem. 2006, 118, 6137 – 6140; Angew. Chem. Int. Ed.
2006, 45, 5991 – 5994; f) C. Nevado, D. J. Cµrdenas, A. M.
Echavarren, Chem. Eur. J. 2003, 9, 2627 – 2635; g) K. C. Nic-
olaou, G. S. Tria, D. J. Edmonds, Angew. Chem. 2008, 120, 1804 –
1807; Angew. Chem. Int. Ed. 2008, 47, 1780 – 1783.
see: a) A. W. Sromek, M. Rubina, V. Gevorgyan, J. Am. Chem.
Soc. 2005, 127, 10500 – 10501; b) Y. Xia, A. S. Dudnik, V.
Gevorgyan, Y. Li, J. Am. Chem. Soc. 2008, 130, 6940 – 6941;
c) A. S. K. Hashmi, T. M. Frost, J. W. Bats, J. Am. Chem. Soc.
2000, 122, 11553 – 11554; d) H. Rabaâ, B. Engels, T. Hupp,
A. S. K. Hashmi, Int. J. Quantum Chem. 2007, 107, 359 – 365;
e) A. S. K. Hashmi, J. P. Weyrauch, W. Frey, J. W. Bats, Org. Lett.
2004, 6, 4391 – 4394; f) A. S. K. Hashmi, M. Rudolph, S. Schy-
mura, J. Visus, W. Frey, Eur. J. Org. Chem. 2006, 4905 – 4909.
[18] When the reaction of (Z)- or (E)-3a was carried out with
10 mol% of AuCl3/AgSbF6, the reaction proceeded faster
(10 min) than the reaction with [AuClPPh3]/AgSbF6 (1 h) to
give the product 4a in somewhat lower yield (32% from (Z)-3a,
59% from (E)-3a).
[12] The geometry of the deuterated double bond was confirmed by
NOE experiments.
[13] Insertion of the gold-stabilized cationic intermediates into sp3
À
C H bonds is rare, see: Y. Horino, T. Yamamoto, K. Ueda, S.
Kuroda, F. D. Toste, J. Am. Chem. Soc. 2009, 131, 2809 – 2811,
and references therein.
[14] We cannot completely rule out the possibility that in the gold-
catalyzed reaction the second cyclization occurred (intermediate
E in Scheme 2) at the a position of the metal followed by
elimination of the gold catalyst.
À
À
[19] For an example of ligand control of C H versus aliphatic C C
migration reaction of Rh carbenoids, see: M. Vitale, T. Lecourt,
C. G. Sheldon, V. K. Aggarwal, J. Am. Chem. Soc. 2006, 128,
2524 – 2525.
[15] The configuration of the Diels–Alder adduct
5 could be
explained by the consideration that the reaction proceeds
through s-cis conformation of the siloxy diene moiety in H.
[16] The Diels–Alder reactions of (Z)-3d, (Z)-3i, and (Z)-7 were
examined to give corresponding adducts in 51%, 99%, and 97%
yields, respectively.
4272
www.angewandte.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2010, 49, 4269 –4272