Efficient control of π-alkyne and vinylidene complex pathways for the W(CO)5(L)-catalyzed synthesis of two types of nitrogen-containing bicyclic compounds

Article abstract of DOI:10.1021/ja0782605

When ω-acetylenic dienol silyl ethers containing NMs part in the tether were treated with a catalytic amount of W(CO)₆ under photoirradiation, 2-azabicyclo[3.3.0]octanes were obtained in good yield via π-alkyne complexes. On the other hand, treatment of the same substrates with a catalytic amount of W(CO)₆ in the presence of n-Bu₃N under the same reaction conditions gave 3-azabicyclo[3.3.0]octanes in good yield exclusively via vinylidene complexes. Thus, the π-alkyne and vinylidene complex pathways are easily controlled by using a catalytic amount of W(CO)₅(L) and an amine. Copyright

Full text of DOI:10.1021/ja0782605

Published on Web 12/22/2007
Efficient Control of π-Alkyne and Vinylidene Complex Pathways for the
W(CO)5(L)-Catalyzed Synthesis of Two Types of Nitrogen-Containing Bicyclic
Compounds
Yuji Onizawa, Hiroyuki Kusama, and Nobuharu Iwasawa*
Department of Chemistry, Tokyo Institute of Technology, O-okayama, Meguro-ku, Tokyo 152-8551, Japan
Received October 29, 2007; E-mail: niwasawa@chem.titech.ac.jp
Table 1. W(CO)5(L)-Catalyzed Reaction of Dienol Silyl Ethers
Recently, electrophilic activation of alkynes through π-complex
1a,b
formation has extensively been studied for the construction of useful
cyclic carbon skeletons using a variety of transition-metal complexes
1d,e
1e
such as Au(I),1a-e Au(III),1a,c,e Pt(II),1a,b,
Ru(II),1a,b, and so
on.2 Utilization of vinylidene complexes generated from terminal
alkynes has also emerged as an attractive method for the unique
transformations of terminal alkynes,3 however, a limited number
of examples have been reported of their use for catalytic C-C bond
formations.4,5 Moreover, control of these two reaction pathways of
terminal alkynes simply by slightly changing the reaction conditions
has rarely been achieved, in particular, for the catalytic construction
of carbon skeletons (eq 1).6 In this paper is described successful
control of π-alkyne- and vinylidene-complex pathways in the
W(CO)5(L)-catalyzed cyclization of terminal alkynes bearing the
siloxy diene moiety for the construction of synthetically useful
2-aza- and 3-azabicyclo[3.3.0]octane skeletons, respectively.
yield (%)
W(CO)6
(mol %)
additive
2
entry
X
(100 mol %)
time
(
R
-Ph/
â
-Ph)
3
1
2
3
Ts
1a
10
100
100
-
Et3N
n-Bu3N
1.5 h
68 (67:33)
0
15 min
1 h
(15 min)a (4)a
0
0
80
57
(73)a
81
0
32
0
61
93
92
4
5
6
7
8
100
10
10
10
10
10
3
DABCOb 40 min
Et3N
n-Bu3N
-
Et3N
0
0
0
2 h
2 h
1.5 h
2 h
2 h
Ms 1b
85 (60:40)
0
0
0
9
10
n-Bu3N
n-Bu3Nc
3.5 h
a Dilution conditions (0.01 M). b Run using 50 mol %. c Run using 30
mol %.
According to the previously established protocol for the W(CO)5-
(L)-catalyzed geminal carbofunctionalization,7 we first examined
the reaction of ω-acetylenic dienol silyl ether 1a containing NTs
part in the tether. When the reaction was carried out with 10 mol
% of W(CO)6 in toluene in the presence of MS 4A under photo-
irradiation, the desired 2-azabicyclo[3.3.0]octane 2a was obtained
in 68% yield as a mixture of diastereomers (Table 1, entry 1). Quite
interestingly, treatment of 1a with 100 mol % of W(CO)6 in the
presence of 100 mol % of NEt3 under the same reaction conditions
gave another bicyclic compound 3a, which was found to have
3-azabicyclo[3.3.0]octane skeleton, in 80% yield without formation
of 2a (entry 2). Other amines such as n-Bu3N and DABCO were
also effective for this reaction (entries 3, 4). However, when the
amount of W(CO)6 was reduced to 10 mol %, the yield of the 3-aza
derivative 3a became considerably lower (entries 5, 6). Further
examination of several reaction parameters revealed that use of
N-Ms derivative 1b instead of N-Ts derivative 1a improved the
yield of the products considerably. Thus, either reaction in the
absence or presence of n-Bu3N proceeded efficiently even with 10
mol % of W(CO)6 to give 2-aza- or 3-azabicyclo[3.3.0]octane in
high yield (entries 7, 9). The latter reaction proceeded even with 3
mol % of W(CO)6 without significantly decreasing the yield (entry
10). The structure of 3b was confirmed by X-ray analysis after
hydrolysis of the silyl enol ether moiety.
Scheme 1. Proposed Reaction Mechanism
[3.3.0]octane 2. On the other hand, formation of 3-azabicyclo[3.3.0]-
octane derivative 3 by the reaction in the presence of the amine is
more complex and could be explained as follows: the amine
facilitated isomerization of π-alkyne complex A to their vinylidene
complex C,8 and then, nucleophilic attack of the enol silyl ether
part to the vinylidene carbon occurred to afford zwitterionic
intermediate D. Then, the resulting alkenyl metallic species reacted
with the R,â-unsaturated silyloxonium moiety at the position â to
the metal to generate the bridged-carbene complex intermediate
E, which further underwent 1,2-alkyl migration assisted by electron
donation from the nitrogen atom to give 3-azabicyclo[3.3.0]octane
The proposed reaction mechanism is shown in Scheme 1. The
reaction in the absence of the amine is thought to proceed in a
similar manner as previously proposed.7 Thus, the alkenyl metallic
moiety in the zwitterionic intermediate B, produced by 5-endo
nucleophilic cyclization of the enol silyl ether part to the π-alkyne
complex A, attacked the R,â-unsaturated silyloxonium moiety at
the position â to the metal to generate bicyclic unstabilized carbene
complex, which underwent a 1,2-hydrogen shift to give 2-azabicyclo-
9
802
J. AM. CHEM. SOC. 2008, 130, 802-803
10.1021/ja0782605 CCC: $40.75 © 2008 American Chemical Society

C O M M U N I C A T I O N S
Table 2. W(CO)5(L)-Catalyzed Reaction of Dienol Silyl Ethers
(1b-g)
of tricyclic product were obtained in reasonable yield without
problem (eq 4).
W(CO)6
(mol %)
n-Bu3N
(mol %)
yield (%)
-R/ -R)
entry
R
R
′
(
R
â
In summary, we have succeeded in controlling the π-alkyne and
vinylidene complex pathways by using a catalytic amount of
W(CO)5(L) and an amine. Very rare control of these two catalytic
reaction pathways simply by slightly changing the reaction condi-
tions was achieved. Control of π-alkyne and vinylidene complex
pathways can be a new method for the catalytic transformation of
alkyne to afford two types of products starting from the same
terminal alkynes.
1
Ph
H
1b
1c
1d
10
3
5
-
30
-
2b: 85 (60:40)
3b: 92
2c: 70 (60:40)
3c: 82
2d: 64 (40:60)
3d: 74
2e: 65 (47:53)
3e: 80
2
3
4
5
6
2-furyl
1-naphthyl
Ph
H
H
5
50
-
30
10
30
5
10
10
10
10
100
-
Me 1e
50
-
i-Pr
H
H
1f
2f: 67 (60:40)a
3f: 50 (2f: 10%)b
2g: 74 (60:40)a
3g: 59 (2g: 11%)b
10
-
Acknowledgment. This research was partly supported by a
Grant-in-Aid for Scientific Research from Ministry of Education,
Culture, Sports, Science and Technology of Japan. Y.O. has been
granted a Research Fellowship of the Japan Society for the
Promotion of Science for Young Scientists. We thank Central Glass
Co., Ltd. for generous gift of trifluoromethanesulfonic acid. We
also thank Ms. Sachiyo Kubo for performing X-ray analysis.
c-hexyl
1g
10
a Dilution conditions (0.01 M). b Dilution conditions (0.01 M) in hexane.
derivative 3. W(CO)5(L) was regenerated at the last step, and thus
the reaction proceeded catalytically.
To support this proposed mechanism in the presence of the
amine, we carried out deuterium- and 13C-labeling experiments.
When the deuterated substrate 1a-d was subjected to the same
reaction conditions, 3-azabicyclo[3.3.0]octane derivative 3a-d with
the deuterium at the 5-position (46% D incorporation) was obtained
in 82% yield (other positions were not deuterated). The reaction in
the presence of 10 equiv of D2O was also examined to prevent
H-D exchange of the terminal alkyne proton, and the degree of
deuterium incorporation increased to >95% (80% yield) (eq 2).
More significantly, when the reaction of 13C-labeled substrate 1b-
13C was examined, 3-azabicyclo[3.3.0]octane derivative 3b-13C with
the 13C at the 2-position was obtained in 86% yield (eq 3). These
results are consistent with the proposed mechanism; that is, the
reaction proceeded via vinylidene complex formation and 1,2-alkyl
migration from intermediate E.
Supporting Information Available: Preparative methods and
spectral and analytical data of compounds 1-3 (PDF) and X-ray data
for the derivatives of 2a and 3b (CIF). This material is available free
of charge via the Internet at http://pubs.acs.org.
References
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(6) We have already succeeded in controlling π-alkyne- and vinylidene-
complex pathways in the W(CO)5(L)-promoted reaction of o-ethynylphenyl
ketone derivatives, but the reaction via vinylidene complex was stoichio-
metric: from π-alkyne complex, see: (a) Iwasawa, N.; Shido, M.; Kusama,
H. J. Am. Chem. Soc. 2001, 123, 5814. (b) Kusama, H.; Funami, H.; Shido,
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K.; Kusama, H. J. Am. Chem. Soc. 2000, 122, 10226. Ohe and Uemura
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Next, generality of this control of π-alkyne and vinylidene
complex pathways was examined with several substrates, with the
results being summarized in Table 2. When substrates having an
aryl group at the diene terminus were employed, the corresponding
2-azabicyclo[3.3.0]octanes 2 and 3-azabicyclo-[3.3.0]octanes 3 were
obtained in good yield by carrying out the reaction in the absence
or presence of n-Bu3N, respectively (entries 1-3). Even the reaction
of a tetrasubstituted diene 1e proceeded smoothly to afford the
corresponding substituted 2- and 3-azabicyclo[3.3.0]octane in good
yield (entry 4). Alkyl-substituted dienes could also be employed
to give the corresponding bicyclic compounds in reasonable yield
(entries 5 and 6). In these cases, small amounts of 2-aza derivatives
were obtained in the amine-promoted reaction.
Additionally, the reaction could be applied to a dienol silyl ether
1h having a cyclohexenyl group at the diene moiety, and two types
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