Cyclooctanone synthesis via a formal [6+2] cycloaddition reaction of a dicobalt acetylene complex

Article abstract of DOI:10.1016/j.tetlet.2010.05.120

An efficient formal [6+2] cycloaddition reaction of a new six-carbon unit with enol silyl ether was developed on the basis of a dicobalt hexacarbonyl propargyl cation species. Under the influence of EtAlCl₂, 6-benzoyloxy-2-(triisopropylsilyloxy)-1-hexen-4-yne-dicobalthexacarbonyl reacted with enol triisopropylsilyl ethers to yield 7-(triisopropylsilyloxy)-3-cyclooctyn-1-one-dicobalthexacarbonyl derivatives in good yield. The reactions with cyclic enol silyl ethers as well as acyclic enol silyl ethers exhibited remarkably high diastereoselectivity.

Full text of DOI:10.1016/j.tetlet.2010.05.120

Tetrahedron Letters 51 (2010) 3983–3986
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Tetrahedron Letters
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Cyclooctanone synthesis via a formal [6+2] cycloaddition reaction
of a dicobalt acetylene complex
Katsuhiko Mitachi a, Tadashi Shimizu a, Masaaki Miyashita b, Keiji Tanino a,
*
a Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan
b Department of Applied Chemistry, Faculty of Engineering, Kogakuin University, Hachioji 192-0015, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient formal [6+2] cycloaddition reaction of a new six-carbon unit with enol silyl ether was
developed on the basis of a dicobalt hexacarbonyl propargyl cation species. Under the influence of EtAl-
Cl2, 6-benzoyloxy-2-(triisopropylsilyloxy)-1-hexen-4-yne-dicobalthexacarbonyl reacted with enol triiso-
propylsilyl ethers to yield 7-(triisopropylsilyloxy)-3-cyclooctyn-1-one-dicobalthexacarbonyl derivatives
in good yield. The reactions with cyclic enol silyl ethers as well as acyclic enol silyl ethers exhibited
remarkably high diastereoselectivity.
Received 6 May 2010
Revised 20 May 2010
Accepted 26 May 2010
Available online 1 June 2010
Ó 2010 Elsevier Ltd. All rights reserved.
The development of an efficient synthetic method for medium-
sized alicyclic compounds has been one of the most challenging
subjects in organic chemistry. It has been well recognized that con-
struction of eight-membered rings,1 which are found as the core
skeleton of many biologically active compounds, is much more dif-
ficult than that of five-, six-, or seven-membered rings. Thus, both
nonbonding interactions and the entropic effects impede closure of
an eight-membered ring and promote intermolecular reactions.
On the other hand, we reported a novel method for the stereose-
lective synthesis of cycloheptanones via a formal [5+2] cycloaddi-
tion reaction using dicobalt acetylene complex2 1 as a five-carbon
unit (Scheme 1).3 The reaction proceeds through intermolecular
addition of enol triisopropylsilyl (TIPS) ether with the dicobalt
propargyl cation A (Nicholas reaction)4 giving rise to the silyloxoni-
um ion B which in turn undergoes an intramolecular addition reac-
tion. In this transformation, the large bond angles5 of the dicobalt
acetylene complex moiety were essential to avoid the formation
of a five-membered ring via an intramolecular cyclization reaction
of the cation intermediate A. In addition, the rigid conformation of
the dicobalt acetylene complex moiety may play an important role
to control the stereochemistry in the cyclization step of the inter-
mediate B.
as a six-carbon unit of an intramolecular formal [6+2] cycloaddi-
tion reaction promoted by a Rh(I) catalyst,7 the intermolecular
version of the cycloaddition reaction has not been reported. On
the other hand, 1,3,5-cycloheptatriene,8 tropone,9 and 1,3,5-cyclo-
octatriene10 serve as a useful six-carbon unit of intermolecular
cycloaddition reactions, but the products arising from the [6+2]
cycloaddition reaction with an olefin or an acetylene always pos-
sess
a
bicyclo[4.2.1]nonane or
a
bicyclo[4.2.2]decane carbon
framework.
OTIPS
O
TIPSO
Me
TIPSO
EtAlCl2
CH2Cl2
+
Co(CO)3
Co(CO)3
Co(CO)3
Me
Co(CO)3
BzO
1
2
84% (cis:trans = 93:7)
OTIPS
OTIPS
TIPSO
TIPSO
Co
Co
Co
R
R
Co
While cycloheptanone 2 could be transformed into cycloocta-
none 3 via the one-carbon ring expansion protocol of Shioiri,6 we
became intrigued with the possibility of a formal [6+2] cycloaddi-
tion reaction for the direct synthesis of cyclooctanone derivatives
(Scheme 2).
A
B
O
TMSCHN2 TIPSO
EtAlCl2
O
TIPSO
+
There has been few examples of [6+2] cycloaddition reactions
which are applicable for the synthesis of a monocyclic eight-
2
(cis)
Co(CO)3
Co(CO)3
76% (94:6)
Me
Me
Co(CO)3
Co(CO)3
then CSA
membered compound. While an
a-vinylcyclobutanone was used
4
3
* Corresponding author. Tel.: +81 11 706 2705; fax: +81 11 706 4920.
E-mail address: ktanino@sci.hokudai.ac.jp (K. Tanino).
Scheme 1. Synthesis of cyclooctanone derivatives via a formal [5+2] cycloaddition
reaction and one-carbon ring expansion.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.05.120

3984
K. Mitachi et al. / Tetrahedron Letters 51 (2010) 3983–3986
Table 1
OTIPS
OTIPS
Stereoselective synthesis of cyclooctanone derivatives by formal [6+2] cycloaddition
reactionsa
TIPSO
R
TIPSO
MXn
Entry Enol silyl ether Productb
Yieldc
(cis:trans)
+
Co(CO)3
Co(CO)3
Co(CO)3
R
BzO
Co(CO)3
TIPSO
TIPSO
O
C
5
9a
91% (ꢀ)
Me
Me
1
2
3
4
5
6
O
OTIPS
Me
Me
Co(CO)3
TIPSO
R
TIPSO
R
Co(CO)3
TIPSO
O
Co(CO)3
Co(CO)3
Co(CO)3
Co(CO)3
TIPSO
D
9b
96% (ꢀ)
Co(CO)3
Scheme 2. The formal [6+2] cycloaddition reaction of enol silyl ether and dicobalt
acetylene complex 5.
Co(CO)3
TIPSO
Me
O
TIPSO
Me
We herein report that the use of the hexacarbonyl dicobalt acet-
ylene complex 5 as a six-carbon unit opens the door to the stereo-
selective synthesis of both mono- and bicyclic cyclooctanone
derivatives via an intermolecular formal [6+2] cycloaddition reac-
tion. The six-carbon unit 5 was prepared as shown in Scheme
3.11 Treatment of enol silyl ether 6 with NBS afforded an insepara-
ble mixture of allyl bromide 7a and vinyl bromide 7b in a 3:2 ratio.
The mixture was subjected to the copper-catalyzed cross-coupling
reaction12 with propargyl benzoate, resulting in the selective con-
sumption of 7a. The six-carbon unit 5 was obtained in quantitative
yield by the reaction of the coupling product 8 with Co2(CO)8.
The formal [6+2] cycloaddition reactions of 5 with several enol
silyl ethers were examined under the influence of EtAlCl2, and the
desired cycloadducts were obtained in good to high yields (Table
1).13 It is noteworthy that no by-product arising from intramolecu-
lar cyclization or homo-coupling of the cobalt complex was de-
tected, which allowed us to perform the reaction with 1.1 equiv
of the six-carbon unit. In addition, the present reactions afforded
satisfactory results without using a high dilution technique, which
is often employed to decrease the probability of an encounter
between the reactive centers of two different molecules.
Stereochemical features of the formal [6+2] cycloaddition reac-
tions are similar to those of the previously described formal [5+2]
cycloaddition reactions.3,14 Thus, acyclic enol silyl ethers mainly
afforded the products 9c, 9d, and 9e in which the silyloxy group
and the alkyl substituent on the neighboring carbon atom are ar-
ranged cis to each other (entries 3–5). On the other hand, trans-
fused bicyclic compound 9f was obtained from a cyclic enol silyl
ether as a single isomer (entry 6).
These results can be rationalized by the transition state models
which correspond to the intramolecular cyclization step of a sily-
loxonium ion intermediate D in Scheme 2. Taking into account
the rigidity as well as the bulkiness of the dicobalt hexacarbonyl
9c
73% (88:12)
Co(CO)3
Co(CO)3
TIPSO
Br
O
TIPSO
9d
68% (singled)
Co(CO)3
Co(CO)3
Br
TIPSO
Ph
O
TIPSO
Ph
9e
83% (86:14)
Co(CO)3
Co(CO)3
OTIPS
O
TIPSO
H
9f
81% (singled)
Co(CO)3
Co(CO)3
a
b
c
The typical procedure is described in Ref. 13.
Structures of major diastereomers are depicted.
Diastereomeric ratio determined by proton NMR spectra.
d
Minor diastereomers were not detected by proton NMR spectra.
(CO)3Co
(CO)3Co
OTIPS
(CO)3Co
(CO)3Co
OTIPS
R'
H
H
+
O
SiiPr3
R
R
+
R'
O
SiiPr3
TS-1
TS-2
Figure 1. Transition state models of the cyclization reactions.
OTIPS
OTIPS
Br
OTIPS
Br
NBS
acetylene moiety, two transition state models in which the R group
occupies an equatorial position can be depicted (Fig. 1). In these
models, the antiperiplanar transition state TS-1 may be favored
+
hexane
6
7a
7b
(3 : 2)
over the synclinal transition state TS-2 because of the greater
*
OTIPS
p
–
p
orbital overlap between the oxonium ion and the enol silyl
OTIPS
ether moiety.15
OBz
CuI
Bu4NI
K2CO3
The configurations of the cyclooctanones were determined as
follows. Since the major diastereomer of adduct 9c was identical
with cyclooctanone 43 in Scheme 1, the cis relationship between
the methyl group and the silyloxy group was confirmed, which also
suggested the preferential formation of the cis isomer of 9d and 9e.
The stereostructure of bicyclic product 9f was unambiguously
established by X-ray crystallographic analysis after transformation
Co2(CO)8
CH2Cl2
Co(CO)3
Co(CO)3
DMF
BzO
BzO
8
5
99%
42% from 6
Scheme 3. Preparation of the six-carbon unit.

K. Mitachi et al. / Tetrahedron Letters 51 (2010) 3983–3986
3985
In conclusion, a new method for the stereoselective synthesis of
cyclooctanone derivatives was developed on the basis of a formal
[6+2] cycloaddition reaction using a dicobalt acetylene complex
5. The cobalt complex moiety of the products can be transformed
into a maleic anhydride by treating with CAN (Scheme 4), while
the corresponding olefin is obtained by the decomplexation proto-
col of Isobe18 (Eq. 1). Synthetic studies on natural products having
an eight-membered ring are under progress in our laboratory.
OCOAr
TIPSO
H
(NH4)2Ce(NO3)6
CaCO3
1) DIBAL, CH2Cl2
85%
9f
2) p-Br-C6H4COCl
DMAP, CH 2Cl2
69%
acetone-H2O
Co(CO)3
Co(CO)3
10
O
O
O
O
TIPSO
TIPSO
Me
TIPSO
Me
Bu3SnH
Br
ð1Þ
O
toluene
100 °C
Co(CO)3
Co(CO)3
H
Me
Me
O
9a
78%
11
O
88%
Acknowledgments
This work was partially supported by the Global COE Program
(Project No. B01: Catalysis as the Basis for Innovation in Materials
Science) and Grant-in-Aid for Scientific Research on Innovative
Areas (Project No. 2105: Organic Synthesis Based on Reaction Inte-
gration) from the Ministry of Education, Culture, Sports, Science
and Technology, Japan.
Scheme 4. Determination of the configuration of 9f.
into maleic anhydride 11 (Scheme 4). Reduction of ketone 9f with
DIBAL afforded a secondary alcohol as a single isomer which in
turn was acylated with p-bromobenzoyl chloride. Maleic anhy-
dride 11 was obtained by treating dicobalt acetylene complex 10
with an excess amount of ceric ammonium nitrate (CAN).3,14,16
In connection with application to the total synthesis of natural
products having an eight-membered ring, we next explored the
cycloaddition reaction using six-carbon unit 12 which was pre-
pared in a similar manner from 3,3-diethoxy-1-propyne. Surpris-
ingly, the reaction of 12 with enol silyl ether failed to give
cyclooctanone 13, and cyclohexanone 14 was obtained through
intramolecular cyclization of the cationic intermediate E (Scheme
5). The result indicates that the bond angles of the dicobalt acety-
lene complex moiety are not large enough to prevent the formation
of a six-membered ring.17 On the other hand, six-carbon unit 5 did
not give the corresponding product 15 even in the absence of enol
silyl ether. Although the origin of the different behavior between
12 and 5 is not clear at this point, it is important to design a six-
carbon unit which does not undergo intramolecular cyclization.
References and notes
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2. For reviews of cyclic dicobalt acetylene complexes, see: (a) Green, J. R. Eur. J.
Org. Chem. 2008, 6053–6062; (b) Hess, W.; Treutwein, J.; Hilt, G. Synthesis 2008,
1, 3537–3562; see also, Nagumo, S.; Ishii, Y.; Sato, G.; Mizukami, M.; Imai, M.;
Kawahara, N.; Akita, H. Tetrahedron Lett. 2009, 50, 26–28. and references
therein.
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702; (c) Green, J. R. Curr. Org. Chem. 2001, 5, 809–826; (d) Fryatt, R.; Christie, D.
R. J. Chem. Soc., Perkin Trans. 1 2002, 447–458; (e) Teobald, B. J. Tetrahedron
2002, 58, 4133–4170. and references therein.
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7816; see also: Montero-Campillo, M.; Rodriguez-Otero, J.; Cabaleiro-Lago, E.
Tetrahedron 2008, 64, 6215–6220.
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Achard, M.; Tenaglia, A.; Buono, G. Org. Lett. 2005, 7, 2353–2356; (c) Ura, Y.;
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and references therein.
OTIPS
OTIPS
TIPSO
Me
EtAlCl2
CH2Cl2
+
EtO
EtO
Co(CO)3
Co(CO)3
Co(CO)3
Co(CO)3
Me
10. Achard, M.; Mosrin, M.; Tenaglia, A.; Buono, G. J. Org. Chem. 2006, 71, 2907–
2910.
EtO
11. Preparation of six-carbon unit 5: A mixture of enol silyl ether 6 (1.5 g, 7.2 mmol)
and powdered NBS (1.5 g, 8.6 mmol) in hexane (7.2 mL) was stirred at 60 °C for
40 min. Filtration of the reaction mixture followed by evaporation gave a
mixture of bromides 7a and 7b. After purification by passing through a short
column of silica gel, which was pretreated with N,N-dimethylaniline, the
product was stirred with propargyl benzoate (0.53 g, 3.3 mmol), CuI (30 mg,
0.16 mmol), Bu4NI (0.12 g, 0.32 mmol), and K2CO3 (1.1 g, 8.3 mmol) in DMF
(18.4 mL) at rt for 13 h. A saturated aq NH4Cl was added, and the mixture was
vigorously stirred for 1.5 h. Usual workup followed by purification by silica gel
column chromatography (hexane/ether = 9:1) afforded 1.04 g (42% from enol
silyl ether 6) of propargyl ester 8. To a solution of Co2(CO)8 (1.1 g, 3.4 mmol) in
CH2Cl2 (3 mL) was added a solution of 8 (1.0 g, 2.8 mmol) in CH2Cl2 (2.5 mL) at
rt. After stirring for 1 h, the mixture was filtered through a plug of cotton.
Concentration under reduced pressure followed by purification by silica gel
column chromatography (hexane/ether = 9:1) afforded 1.8 g (99%) of dicobalt
acetylene complex 5. 1H NMR (CDCl3, 270 MHz) d 1.00–1.38 (m, 21H), 3.62 (s,
2H), 4.25 (s, 1H), 4.27 (s, 1H), 5.56 (s, 2H), 7.44 (t, J = 7.6 Hz, 2H), 7.57 (t,
J = 7.6 Hz, 1H), 8.12 (d, J = 7.6 Hz, 2 H); 13C NMR (CDCl3, 67.8 MHz) d 12.59 (3C),
18.07 (6C), 42.35, 65.98, 90.91, 93.04, 94.98, 128.27 (3C), 129.59, 132.97,
156.72, 166.28, 199.20 (6C).
12
E
O
O
TIPSO
Me
Me
EtO
Co(CO)3
Co(CO)3
Co(CO)3
Co(CO)3
14
60% (NMR yield)
EtO
13
O
EtAlCl2
CH2Cl2
complex mixture
5
Co(CO)3
Co(CO)3
15
12. Jeffery, T. Tetrahedron Lett. 1989, 30, 2225–2228.
13. Typical procedure for the formal [6+2] cycloaddition reaction: To a solution of 2-
methyl-1-(triisopropylsilyloxy)propene (0.13 mL, 0.48 mmol) and six-carbon
Scheme 5. The different behavior of cobalt complexes 12 and 5.

3986
K. Mitachi et al. / Tetrahedron Letters 51 (2010) 3983–3986
unit 5 (0.33 g, 0.50 mmol) in CH2Cl2 (0.50 mL) was added a 0.96 M hexane
13.03 (3C), 18.31 (3C), 18.35 (3C), 23.73, 27.31, 42.10, 45.32, 48.03, 49.27,
75.61, 87.53, 93.67, 112.07, 199.17 (6C), 202.98; HRMS (EI) calcd for
solution of EtAlCl2 (1.2 mL, 1.1 mmol) at ꢀ78 °C. After stirring the reaction
mixture at ꢀ23 °C for 20 min, a saturated aq. potassium sodium tartrate was
added. The mixture was stirred vigorously at rt under argon atmosphere for
30 min and separated. The aqueous layer was extracted with ether, and the
combined organic layer was dried over MgSO4. Concentration under reduced
pressure followed by purification by silica gel column chromatography
(hexane then hexane/ether = 20:1) afforded 0.26 g (91%) of cycloadduct 9a.
IR (neat) 3076, 2947, 2892, 2868, 2091, 2050, 2016, 1971, 1713, 1464, 1387,
C
25H34O8SiCo2: 608.0687, found: 608.0710.
14. Tanino, K.; Shimizu, T.; Miyama, M.; Kuwajima, I. J. Am. Chem. Soc. 2000, 124,
6116–6117.
15. This type of antiperiplanar model was originally suggested for an
intermolecular addition reaction of enol silyl ethers and acetals: Murata, S.;
Suzuki, M.; Noyori, R. J. Am. Chem. Soc. 1980, 102, 3248–3249.
16. Schottelius, M. J.; Chen, P. Helv. Chim. Acta 1998, 81, 2341–2347.
1217, 1195, 1110, 1088, 1067, 1015, 883 cmꢀ1
;
1H NMR (CDCl3, 270 MHz) d
17. Example of a six-membered dicobalt acetylene complex: Schreiber, S. L.;
1.06 (s, 3H), 1.08 (br s, 21H), 1.17 (s, 3H), 2.63 (dd, J = 3.0 and 16.2 Hz, 1H), 2.96
(dd, J = 8.9 and 16.2 Hz, 1H), 3.02 (s, 2H), 3.87 (d J = 16.5 Hz, 1H), 4.04 (d,
J = 16.5 Hz, 1H), 4.19 (dd, J = 3.0 and 8.9 Hz, 1H); 13C NMR (CDCl3, 67.5 MHz) d
Sammakia, T.; Crowe, W. E. J. Am. Chem. Soc. 1986, 108, 3128–3130.
18. Hosokawa, S.; Isobe, M. Teterahedron Lett. 1998, 39, 2609–2612.