Formal [4+2] cycloaddition of cyclobutanones bearing alkyne-cobalt complex at their 3-positions

Article abstract of DOI:10.1016/j.tetlet.2011.11.067

Cyclobutanones bearing an alkyne-cobalt complex at their 3-positions reacted with aldehydes to give formal [4+2] cycloadducts by using tin(IV) chloride as a Lewis acid. Highly substituted tetrahydropyrone derivatives were stereoselectively prepared by thi

Full text of DOI:10.1016/j.tetlet.2011.11.067

Tetrahedron Letters 53 (2012) 432–434
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Tetrahedron Letters
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Formal [4+2] cycloaddition of cyclobutanones bearing alkyne–cobalt complex
at their 3-positions
⇑
Mizuki Kawano, Takaaki Kiuchi, Jun-ichi Matsuo , Hiroyuki Ishibashi
School of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Cyclobutanones bearing an alkyne–cobalt complex at their 3-positions reacted with aldehydes to give
formal [4+2] cycloadducts by using tin(IV) chloride as a Lewis acid. Highly substituted tetrahydropyrone
derivatives were stereoselectively prepared by this method.
Received 18 October 2011
Revised 11 November 2011
Accepted 14 November 2011
Available online 19 November 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
[4+2] Cycloaddition
Alkyne–cobalt complex
Cyclobutanone
Lewis acid
Tetrahydropyrone
Cyclobutanones are important synthetic intermediates in or-
ganic synthesis.1 We have recently reported that zwitterionic
intermediate 2, which was generated by Lewis acid-catalyzed ring
cleavage of 3-ethoxycyclobutanone 1, reacted with various alde-
hydes,2a allylsilanes,2b silyl enol ethers,2c and imines2d to afford
the corresponding formal [4+2] cycloadducts (Eq. 1). We have also
reported diastereoselective asymmetric [4+2] cycloaddition by
Cyclobutanones 11aꢀc were prepared from amides 7aꢀc by se-
ven steps (Scheme 1). 3-Benzyloxymethylcyclobutanones 8aꢀc
were prepared by [2+2] cycloaddition with ketene iminium ions,5
which were generated from amides 7aꢀc, and allyl benzyl ether.
Protection of the carbonyl group of 8aꢀc with ethylene acetal,
deprotection of the benzyl group of 9aꢀc, and Swern oxidation6
of the resulting primary alcohols gave aldehydes 10aꢀc. Reaction
of aldehydes 10aꢀc with Bestmann–Ohira reagent7 followed by
the deprotection of acetal and complexation with Co2(CO)8 gave
the desired cyclobutanones 11aꢀc.
using 3-alkoxycyclobutanone bearing L-ethyl lactate as a chiral
auxiliary.3 The generation of zwitterionic intermediate 2 was pro-
moted by the alkoxy group at the 3-position of 1. It was then
thought that an alkyne–cobalt complex at the 3-position of cyclo-
butanone 4 would also promote the generation of zwitterionic
First, we explored a suitable Lewis acid for formal [4+2] cycload-
dition between cyclobutanone 11a and benzaldehyde 12 (Table 1).
The desired product 13 was obtained in a 38% yield by using boron
trifluoride etherate (entry 1). Catalysis with titanium(IV) chloride
gave enone 14 in a 32% yield as the major product along with cyc-
loadduct 13 (13%). Tin(IV) chloride was found to catalyze the de-
sired [4+2] cycloaddition most effectively among the Lewis acids
we tested, and 13 was obtained in an 82% yield with high cis-selec-
tivity (cis/trans = 98:2) (entry 3). When ethylaluminum dichloride
was employed, enone 14 was obtained in a 79% yield (entry 4).
Next, the scope and limitations of tin(IV) chloride-catalyzed
[4+2] cycloaddition of cyclobutanone 11a were investigated by
using various aldehydes 15aꢀl (Table 2). 4-Methyl and 4-methoxy-
benzaldehydes reacted with 11a to give the corresponding [4+2]
cycloadducts in 57% and 31% yields, respectively (entries 1 and
2). The use of halogen-substituted benzaldehydes 15cꢀe afforded
the desired products 16cꢀe in high yields (entries 3ꢀ5). These
results suggest that electrophilic aldehydes reacted smoothly. In
comparison with 2-naphtaldehyde 15g, which gave cycloadduct
16g in a 45% yield (entry 7), the reaction with 1-naphtaldehyde
intermediate 5 since an alkyne–cobalt complex stabilizes the
a-
cation (Eq. 2).4 We report herein the formal [4+2] cycloaddition
of cyclobutanones bearing an alkyne–cobalt complex at their
3-positions to afford tetrahydropyrones.
O
LAO
O
O
LA
RCHO
ð1Þ
ð2Þ
OEt
OEt
EtO
R
O
3
1
4
2
O
LAO
LA
RCHO
(CO)3
Co
(CO)3
(CO)3
Co
Co
Co(CO)3
(OC)3Co
Co(CO)3
O
R
5
6
⇑
Corresponding author.
E-mail address: jimatsuo@p.kanazawa-u.ac.jp (J. Matsuo).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.11.067

M. Kawano et al. / Tetrahedron Letters 53 (2012) 432–434
433
Table 2
OBn
(2.0 equiv)
Tin(IV) chloride-catalyzed formal [4+2] cycloaddition of cyclobutanone 11a to various
R
O
Tf2O (1.1 equiv)
O
aldehydes 15aꢀla
2,4,6-collidine (1.2 equiv)
R
R
N
1,2-DCE, reflux
R
then 15% aq. NaOH
OBn
O
7a
7b
: R = Me
8a
8b
: R = Me (93%)
O
: R = (CH2)4
: R = (CH2)4 (80%)
SnCl4
(CO)3
Co
7c: R = (CH2)5
(CO)3
Co
8c: R = (CH2)5 (81%)
R
15a-l
O
CH2Cl2, rt
(OC)3Co
O
R
Co(CO)3
OH
(1.2 equiv)
O R
HO
1) H2, Pd(OH)2
EtOH, rt
11a
16a-l
R
TsOH•H2O (5 mol%)
benzene, reflux
O
2) (COCl)2, DMSO
CH2Cl
;Et3N
OBn
2 , -78 °C
9a
9b
: R = Me (95%)
: R = (CH2)4 (100%)
Yieldb (%)
Cis/transc
9c: R = (CH2)5 (96%)
Entry
15 (R)
15a (4-MeC6H4)
Time (h)
1)
O
P
O
1
2
3
4
5
6
7
8
9
4
10
4
4
4
22
8
6
6
9
57
31
77
83
87
27
45
76
68
42
61
11
>99:1
>99:1
99:1
93:7
91:9
>99:1
>99:1
96:4
91:9
94:6
97:3
98:2
MeO
MeO
15b (4-MeOC6H4)
15c (4-FC6H4)
15d (4-ClC6H4)
15e (4-BrC6H4)
15f (1-naphthyl)
15g (2-naphthyl)
15h (PhCH2CH2)
15i (n-heptyl)
15j (i-Bu)
, K2CO3
R
R
N2
O R
O
MeOH, rt
R
(CO)3
O
Co
2) 1N HCl
Co(CO)3
O
EtOH, reflux
3) Co2(CO)8, CH2Cl2, rt
10a
11a
: R = Me (82%)
: R = Me (89%)
10b: R = (CH2)4 (74%)
10c: R = (CH2)5 (91%)
11b: R = (CH2)4 (82%)
11c: R = (CH2)5 (71%)
10
11
12
15k (i-Pr)
15l (t-Bu)
18
12
Scheme 1. Preparation of cyclobutanone 11aꢀc.
a
b
c
For reaction conditions, see Table 1.
Isolated yield (%).
15f gave the desired adduct 16f in a lower yield (entry 6). Aliphatic
aldehydes 15hꢀk gave the corresponding tetrahydropyrones
16hꢀk (entries 8ꢀ12). Longer reaction time was required for steri-
cally hindered aldehydes. In all of the examples described above,
cycloadducts 16aꢀl were obtained with high cis-selectivity.
Reactions of spirocyclobutanones 11b and 11c also gave the
corresponding cycloadducts 17b and 17c in 64% and 58% yields,
respectively, as a single diastereomer (Table 3).
Decomplexation of alkyne–cobalt complex 13 with cerium(IV)
diammonium nitrate afforded tetrahydropyrone 18 in a 75% yield
(Scheme 2). Reaction of cyclobutanone 19 with benzaldehyde cat-
alyzed by tin(IV) chloride did not proceed. Therefore, the stabiliza-
The stereochemistry was determined by 1H NMR spectra.
Table 3
Tin(IV) chloride-catalyzed formal [4+2] cycloaddition of 2,2-dialkylcyclobutanones
11b and 11c to benzaldehydea
O
R1
R1
R2
R2
(CO)3
Co
O
SnCl4
(CO)3
Co
Ph
O
CH2Cl2
rt, 4 h
(OC)3Co
12
O
Ph
Co(CO)3
11b–c
17b–c
Yieldb (%)
Cis/transc
tion of
a-cation by the alkyne–cobalt complex was important for
Entry
Cyclobutanone 11
these cycloaddition reactions.
In summary, we have developed tin(IV) chloride-mediated
intermolecular [4+2] cycloaddition of cyclobutanones bearing an
1
2
R1, R2 = (CH2)4 (11b)
R1, R2 = (CH2)5 (11c)
64
58
>99:1
>99:1
a
b
c
For reaction conditions, see Table 1.
Isolated yield (%).
The stereochemistry was determined by 1H NMR spectra.
Table 1
Effects of Lewis acidsa
O
O
O
PhCHO
SnCl4
O
CAN(4 equiv)
MeOH, 0 °C
O
(CO)3
Co
(CO)3
(OC)3Co
Ph
O
Ph
Co
(OC)3Co
O
Ph
Ph
13
18
19
cis-
cis-
75%
O
13
Lewis acid
CH2Cl2
(CO)3
Co
Ph
O
Scheme 2. Decomplexation of alkyne–cobalt complex 13.
O
Co(CO)3
12
11a
(CO)3
Co
(OC)3Co
HO
alkyne–cobalt complex at their 3-positions. This formal [4+2]
cycloaddition showed cis-stereoselectivity.
14
Entry
Lewis acid
Conditions
Yieldb (%)
Acknowledgment
13
14
1
2
3
4
BF3-OEt2
TiCl4
SnCl4
rt, 12 h
38
ndc
32
Trace
79
This work was supported by a Grant-in-Aid for Scientific Re-
search from the Ministry of Education, Culture, Sports, Science,
and Technology, Japan.
ꢀ20 °C, 15 min
13
rt, 4 h
82d
Trace
EtAlCl2
ꢀ20 °C to 0 °C, 1 h
a
PhCHO (12, 1.0 equiv), cyclobutanone 11a (1.5 equiv) and Lewis acid (2.0 equiv)
Supplementary data
were employed.
b
Isolated yield (%).
nd = Not detected.
c
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.11.067.
d
Cis/trans = 98:2. The stereochemistry was determined by 1H NMR spectra.

434
M. Kawano et al. / Tetrahedron Letters 53 (2012) 432–434
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