Rh(I)-catalyzed ring-closing reaction of allenynes: Selective construction of cycloheptene, bicyclo[5.3.0]decadienone, and bicyclo[5.2.0]nonene frameworks

Article abstract of DOI:10.1016/j.tetlet.2004.03.160

Highly selective formation of cycloheptene, bicyclo[5.3.0]decadienone, and bicyclo[5.2.0]nonene skeletons from tri- and tetrasubstituted allenynes has been achieved via a Rh(I)-catalyzed ring-closing reaction and proper choice of substrate and/or reaction

Full text of DOI:10.1016/j.tetlet.2004.03.160

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 4117–4121
Rh(I)-catalyzed ring-closing reaction of allenynes:
selective construction of cycloheptene, bicyclo[5.3.0]decadienone,
and bicyclo[5.2.0]nonene frameworks
*
Chisato Mukai, Fuyuhiko Inagaki, Tatsunori Yoshida and Shinji Kitagaki
Faculty of Pharmaceutical Sciences, Kanazawa University, Takara-machi, Kanazawa 920-0934, Japan
Received 19 February 2004; revised 19 March 2004; accepted 24 March 2004
Abstract—Highly selective formation of cycloheptene, bicyclo[5.3.0]decadienone, and bicyclo[5.2.0]nonene skeletons from tri- and
tetrasubstituted allenynes has been achieved via a Rh(I)-catalyzed ring-closing reaction and proper choice of substrate and/or
reaction conditions.
ꢀ
2004 Elsevier Ltd. All rights reserved.
The intramolecular Pauson–Khand reaction (PKR) of
enynes is one of the most powerful tools available for
the construction of bicyclo[3.3.0]octenones and bicy-
clo[4.3.0]nonenones. However, this attractive ring-clos-
ing method generally is not effective for the synthesis of
2.5 mol %
R3
R4
[RhCl(CO) ] or
PhO2S
R3
2 2
R4
[
RhCl(CO)dppp]2
·
toluene, CO
O
R2
PhO S
2
R2
1;2
R1
R1
bicyclo[5.3.0]decenones in large part due to entropic
as well as enthalpic factors, which could impede the
1
2
3
formation of larger-sized rings. Recent efforts from this
laboratory have led to the development of a new and
efficient procedure for the construction of the bicy-
Scheme 1.
3
4
clo[5.3.0]decadienone framework 2 (R ¼ R ¼ H) based
skeletons could be achieved. This letter describes our
preliminary results.
on the Rh(I)-catalyzed intramolecular PKR of allenynes
3
4
4
1
occurs between the distal double bond of the allenic
(R ¼ R ¼ H). This ring-closing reaction selectively
4
According to the previously reported procedures , the
7
allene 3a having a methyl group at the allenic terminus
was treated with 2.5 mol % of [RhCl(CO) ] in refluxing
2 2
toluene under a CO atm to give the desired bicyclic
compound 4a in 19% yield. However, the major product
isolated from the reaction mixture was the seven-mem-
3
4
moiety and the alkyne counterpart of 1 (R ¼ R ¼ H),
resulting in the formation of the bicyclo[5.3.0]decadie-
nones 2 (R ¼ R ¼ H) in moderate to high yields
3
4
5;6
(
Scheme 1).
We then applied this newly developed Rh(I)-catalyzed
ring-closing reaction to tri- and tetrasubstituted alleny-
nes. Depending on the substitution pattern of the allenic
bered compound 5a with the crossed-triene moiety in
8
6
8% yield. Changing the catalyst from [RhCl(CO) ] to
2
2
RhCl(CO)dppp]
2
[ under similar conditions produced 4a
and 5a in 37% and 47% yields, respectively (Scheme 2).
3
4
moiety of 1 (R and/or R ¼ substituent) and/or reaction
8
conditions, the selective construction of (i) 3-alkylidene-
2
9
-vinylcyclohept-1-ene, (ii) bicyclo[5.3.0]deca-1,7-dien-
-one, and (iii) 2-alkylidenebicyclo[5.2.0]non-1(9)-ene
9
;10
The Rh(I)-catalyzed PKR
of allenynes would be
tentatively rationalized in terms of the intermediacy of
the metallacyclopentene intermediate A, which would
collapse to the bicyclo[5.3.0] ring system via insertion of
CO (path a, Scheme 3), followed by reductive elimina-
tion. Alternatively, the methyl hydrogen at the allenic
terminus of the intermediate A would be abstracted via
b-hydride elimination (path b), leading to the formation
Keywords: Pauson–Khand reaction; Cycloisomerization; Bicyclo-
5.3.0]decane; Bicyclo[5.2.0]nonane; Allenyne; Electrocyclic reaction.
9
[
*
Corresponding author. Tel.: +81-76-234-4411; fax: +81-76-234-4410;
e-mail: cmukai@kenroku.kanazawa-u.ac.jp
0
040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.03.160

4118
C. Mukai et al. / Tetrahedron Letters 45 (2004) 4117–4121
PhO S
eliminated path b and made path a exclusively the fa-
vored one.
PhO S
2
2
H
Me
H
Me
H
+
·
TMS
a or b
O
With these considerations in mind, we envisioned that
increasing the CO pressure in the ring-closing reaction
of 3a would facilitate the CO insertion process (path a)
resulting in the preferential formation of the bicy-
clo[5.3.0]decadienone 4a over b-hydride elimination
PhO S
( )4
2
TMS
TMS
3
a
4a
5a
Scheme 2. Reaction conditions: (a) 2.5 mol % [RhCl(CO)
2 2
] , toluene,
(
path b), whereas the ring-closing reaction under a N2
reflux, 1 atm CO, 2.5 h, 4a (19%), 5a (68%); (b) 2.5 mol %
[
RhCl(CO)dppp]
2
, toluene, reflux, 1 atm CO, 6 h, 4a (37%), 5a (47%).
atm (absence of external CO) must produce exclusively
14;15
the triene derivative 5a.
tion of 3a was carried out in the presence of
RhCl(CO) ] at 120 ꢁC under 10 atm of CO (conditions
Thus, the ring-closing reac-
[
PhO S
H
Me
PhO S
2
2 2
2
Me
A) to furnish the desired bicyclic compound 4a in 79%
yield along with a small amount of 5a (8%). It should be
noted that for the preparation of the 10-substituted-bi-
cyclo[5.3.0]decadienone skeleton under conditions A,
·
TMS
O
PhO S
( )4
2
TMS
3a
TMS
[RhCl(CO)dppp] was found to be ineffective. Several
2
allenynes having the RCH functionality at the allenic
4
a
5a
2
PhO S
terminus were submitted to conditions A. The results are
summarized in Table 1, together with those obtained
from the reaction under CO pressure (conditions B) as a
control experiment. The ring-closing reaction of 3a–d
under conditions A consistently produced the corre-
sponding bicyclic compounds 4a–d in a highly selective
manner in acceptable yields. However, conditions A
were shown to be no longer effective for the ring-closing
reaction of tetrasubstituted allenynes, such as 1
PhO S Me
2
2
Rh(I)
Rh
PhO S
H
2
Rh
H C
2
O
H
path a
path b
TMS
TMS
Rh
TMS
B
C
CO insertion
β-elimination
A
3
4
(
R ¼ R ¼ Me in Scheme 1, e.g.), resulting in an
Scheme 3.
intractable mixture, from which only a small amount of
the 3-alkylidene-2-vinylcyclohept-1-ene derivative could
be isolated.
11–13
of the triene derivative (Scheme 3). The latter pro-
cess (path b) was not observed in the case of the Rh(I)-
3
4
catalyzed PKR of 1 (R ¼ R ¼ H), where the lack of a
We next turned our attention to the development of the
selective formation of the cycloheptene derivatives from
methyl group (or its equivalent) at the allenic terminus
Table 1. Rh(I)-catalyzed PKR of 3
R1
PhO2S
PhO2S
H
H
R1
R1
.
R 2
+
H
O
2
.5 mol %
PhO2S
( )4
[RhCl(CO) ]
2
2
R2
R2
3a-d
4a-d
5a-d
Conditions A: 10 atm CO, toluene, 120 °C (bath temperature)
Conditions B: 1 atm CO, toluene, reflux
1
2
1
2
1
n
2
a: R =H, R =TMS; b: R =H, R =Ph; c: R = Pr, R =TMS; d:
1
2
R =Ph, R =TMS
Entry
SM
Conditions
Bicyclo[5.3.0]
Yield (%)
Triene
4:5
4
5
Yield (%)
1
2
3a
3b
3c
3d
A
A
A
A
4a
4b
4c
4d
79
80
67
86
5a
5b
5c
5d
8
8
91:9
91:9
100:0
100:0
a
3
a
––
––
4
5
6
3a
3b
3c
3d
B
B
B
B
4a
4b
4c
4d
19
14
24
79
5a
5b
5c
5d
68
62
22:78
18:82
26:74
92:8
a
b
7
a
70
7
c
8
a
b
c
5
2 2
mol % of [RhCl(CO) ] was used.
1
E/Z ratio (81:19) was determined by H NMR spectrum.
1
E/Z ratio (72:28) was determined by H NMR spectrum.

C. Mukai et al. / Tetrahedron Letters 45 (2004) 4117–4121
4119
3. The ring-closing reaction of the trisubstituted
allenynes 3a–d was carried out in refluxing toluene in the
2
Since the C -vinyl group of 5a could rotate freely
without any serious nonbonding repulsion, the preferred
conformer of 5a is not necessarily the one depicted in
Scheme 2. This is not the case for 5e, where the non-
bonding interaction between the phenylsulfonyl group
and the methyl moiety on the C -vinyl group would
2
2
prevent free rotation of the C -propylene group as well
as make the conformer depicted in Scheme 4 the pre-
ferred one. Thus, 5e could be transformed easily into 6e
via the 4p-electrocyclic reaction.
presence of [RhCl(CO) ] under a N atm (conditions C)
2
2
2
to furnish the corresponding 3-alkylidene-2-vinylcyclo-
hept-1-ene derivatives 5a–d (Table 2). As expected, the
bicyclo[5.3.0]decadienones 4a–c could never be detected
in the reaction mixture (entries 1–3). In the ring-closing
reaction of 3d, the corresponding CO-inserted product
16
4
d (12%) was detected. Thus, we could now develop
the complementary procedure for the construction of
the bicyclo[5.3.0]deca-1,7-dien-9-one and 3-alkylidene-
2-vinylcyclohept-1-ene frameworks, starting from the
same trisubstituted allenynes 3, by changing the reaction
conditions (conditions A and C).
Several tetrasubstituted allenynes were then submitted
to conditions C to confirm the applicability of this novel
tandem cyclization. The results are summarized in Table
3. The terminal alkyne derivative 3f afforded exclusively
In the next phase of this investigation, which involved
the ring-closing reaction of tetrasubstituted allenynes
under conditions C, the tetrasubstituted allenyne 3e
having two methyl groups at the allenic terminus pro-
vided the corresponding cycloheptene 5e in 62% yield
the bicyclo[5.2.0] derivative 6f in refluxing toluene with a
lower yield (58%) compared to 6e, presumably due to its
20;21
instability (entry 1)
. Allenynes 3g,h having methyl
and phenyl groups at the allenic terminus provided 6g,h
in high yields (entries 2 and 3). In the case of 3i, the
triene compound 5i was obtained as a major product
(56%) along with the desired 6i in 12% yield (entry 4).
Higher reaction temperatures did not improve the
chemical yield of 6i. In addition, interconversion
(
80 ꢁC instead of refluxing temperature). This result was
similar to those observed in the cases of the trisubsti-
tuted allenynes 3a–d. Interestingly, and unexpectedly,
17;18
the bicyclo[5.2.0]nonene derivative 6e
the major product (80%), along with a small amount of
e (10%), when a similar ring-closing reaction was per-
was isolated as
between 5i and 6i in the presence of [RhCl(CO)
2
]
2
was
5
formed in refluxing xylene. The formation of 6e could be
interpreted tentatively as occurring via the reversible
thermal 4p-electrocyclic reaction of 5e. In fact, com-
pounds 5e and 6e were heated separately in refluxing
xylene to afford a mixture of 6e and 5e in a ratio of 4–
PhO2S
PhO S
Me
Me
2
Me
Me
+
Ph
5
:1. In addition, transformation of 5e to 6e was found to
19
PhO2S
( )4
2.5 mol %
RhCl(CO) ]
2 2
be accelerated by a catalytic amount of [RhCl(CO) ] ,
Ph
Ph
[
2
2
2 2
although the role of [RhCl(CO) ] in this acceleration is
still uncertain. It should be noted that the triene deriv-
atives 5a–d, obtained from the trisubstituted allenynes
3e
5e
6e
Conditions
Yield
3
a–d, could never be converted into the corresponding
bicyclo[5.2.0]nonene skeleton even in refluxing xylene
for a prolonged period. The difference in reactivity
between 5a and 5e, for example, would be interpreted
provisionally by considering each preferred conformer.
toluene, 80 °C, 20 h
xylene, reflux, 13 h
62%
10%
–
80%
Scheme 4.
Table 2. Rh(I)-catalyzed ring-closing reaction under N
2
R1
PhO2S
H
2.5 mol %
RhCl(CO) ]
R1
[
2
2
R2
H
·
toluene, reflux
PhO2S
( )4
under N
2
R2
(
Conditions C)
3
a-d
5a-d
1
2
Entry
Allenyne 3
R
R
Triene 5
Yield (%)
1
2
3a
3b
3c
3d
H
TMS
Ph
5a
5b
5c
5d
59
65
H
a
n
b
3
c
Pr
Ph
TMS
TMS
66
d;e
57
4
a
b
c
5
mol % of [RhCl(CO)
E/Z ratio (79:21) was determined by H NMR spectrum.
0 mol % of [RhCl(CO) was used.
A small amount of 4d (12%) was obtained.
2 2
] was used.
1
1
2 2
]
d
e
In this case, a mixture of two stereoisomers (E/Z ¼ 39:61), due to the geometry of the C
3
-TMSmethylene group of 2-(E-phenylethenyl)cycloheptene
derivative, was obtained.

4120
C. Mukai et al. / Tetrahedron Letters 45 (2004) 4117–4121
a
Table 3. Rh(I)-catalyzed tandem cycloisomerization–electrocyclization of 3
Entry
Allenyne
Products (yield)
Me
Me
PhO S
2
PhO2S
Me
R
·
·
Me
R
b
1
PhO2S
( )4
R
3
f
5f (––)
6f (58%)
PhO2S
PhO S
2
Me
Ph
PhO2S
( )4
Ph
Ph
2
3
4
3g: R ¼ Ph
5g (––)
5h (––)
5i (56%)
6g (88%)
6h (78%)
6i (12%)
3h: R ¼ 4-NO
2 6 4
C H
3i: R ¼ CO
2
Et
PhO2S
PhO2S
5
·
Ph
PhO2S
( )4
Ph
5
j (91%)
6j (––)
Ph
3
j
a
Reaction was carried out in refluxing xylene under the influence of 2.5 mol % [RhCl(CO
The reaction was carried out in refluxing toluene.
2 2
)] .
b
unsuccessful, presumably due to the weak coordinating
ability of the a,b-unsaturated ester functionality with
the rhodium catalyst. The ring-closing reaction of 3j
having a cyclohexylidene moiety provided the triene 5j,
and not 6j, in high yield (entry 5). The exclusive for-
mation of 5j might reflect the steric repulsion between a
cyclohexene ring and the phenylsulfonyl group, which
would interfere with the transformation of 5j into 6j.
Wender, P. A.; McDonald, F. E. Tetrahedron Lett. 1990,
1, 3691–3694; (b) Mukai, C.; Sonobe, H.; Kim, J. S.;
Hanaoka, M. J. Org. Chem. 2000, 65, 6654–6659.
. For construction of seven- and larger-membered rings via
PKR of enynes with an aromatic ring as a template, see:
3
2
(
a) P ꢀe rez-Serrano, L.; Casarrubios, L.; Dom ꢀı nguez, G.;
P ꢀe rez-Castells, J. Chem. Commun. 2001, 2602–2603; (b)
Krafft, M. E.; Fu, Z.; Bo n~ aga, L. V. R. Tetrahedron Lett.
2
001, 42, 1427–1431; (c) Lovely, C. J.; Seshadri, H.;
Wayland, B. R.; Cordes, A. W. Org. Lett. 2001, 3, 2607–
2610; (d) Barluenga, J.; Sanz, R.; Fa n~ an ꢀa s, F. J. Chem.
Eur. J. 1997, 3, 1324–1336.
In summary, a reliable procedure for not only the con-
struction of the 10-substituted-bicyclo[5.3.0]decadienone
ring system, but also for the preparation of the 3-alkyl-
idene-2-vinylcyclohept-1-ene framework has been
developed by selecting appropriate reaction conditions,
starting from the same trisubstituted allenynes. We have
3
4
. Illuminati, G.; Mandolini, L. Acc. Chem. Res. 1981, 14,
9
5–102.
. (a) Mukai, C.; Nomura, I.; Yamanishi, K.; Hanaoka, M.
Org. Lett. 2002, 4, 1755–1758; (b) Mukai, C.; Nomura, I.;
Kitagaki, S. J. Org. Chem. 2003, 68, 1376–1385.
also succeeded in constructing
[
a novel bicyclo-
5.2.0]nonene framework by the Rh(I)-catalyzed con-
5
2 2
. Brummond et al. have reported the [RhCl(CO) ] -cata-
lyzed PKR of allenynes, which involves four successful
examples of the formation of the bicyclo[5.3.0]decadi-
enone skeleton: Brummond, K. M.; Chen, H.; Fisher, K.
D.; Kerekes, A. D.; Rickards, B.; Sill, P. C.; Geib, S. J.
Org. Lett. 2002, 4, 1931–1934; Brummond, K. M.; Gao,
D. Org. Lett. 2003, 5, 3491–3494.
secutive cycloisomerization and electrocyclic reaction of
tetrasubstituted allenynes. Application of these newly
developed cyclization methods to the synthesis of nat-
ural products is now in progress.
6
7
. For other examples of the formation of the bicy-
clo[5.3.0]decane skeleton via transition metal-catalyzed
PKR of allenynes, see: (a) Shibata, T.; Koga, Y.; Nara-
saka, K. Bull. Chem. Soc. Jpn. 1995, 68, 911–919; (b)
Ahmar, M.; Locatelli, C.; Colombier, D.; Cazes, B.
Tetrahedron Lett. 1997, 38, 5281–5284.
Acknowledgement
This work was supported in part by a Grant-in-Aid for
Scientific Research from the Ministry of Education,
Culture, Sports, Science and Technology, Japan, to
which the authors’ thanks are due.
. The allenynes 3 were prepared from commercially avail-
able 1,7-octadiyne in three or four steps as follows: (i)
EtMgBr, THF, 0 fi 40 ꢁC, then aldehyde or ketone, 0 ꢁC;
n
(
ii) BuLi, TMSCl, THF, )78 ꢁC, then 10% aq HCl (for
i
3
a,c, and d), or PhI, PdCl
2 3 2 2
(PPh ) , CuI, Pr NH, THF (for
References and notes
3b,e,g–j); (iii) PhSCl, Et N, THF, )78 ꢁC; (iv) mCPBA,
3
CH
2
Cl
2
, 0 ꢁC.
1
. For attempts at constructing the bicyclo[5.3.0]decenone
skeleton via the intramolecular PKR of enynes, see: (a)
8. The bicyclo[4.3.0]nonenone derivative could never be
detected in the reaction mixture.

C. Mukai et al. / Tetrahedron Letters 45 (2004) 4117–4121
4121
9
. (a) Jeong, N.; Lee, S.; Sung, B. K. Organometallics 1998,
7, 3642–3644; (b) Jeong, N.; Sung, B. K.; Choi, Y. K. J.
Am. Chem. Soc. 2000, 122, 6771–6772.
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998, 249–250; (b) Kobayashi, T.; Koga, Y.; Narasaka, K.
15. For other examples of transition metal-catalyzed allenyne
cycloisomerizations, see: (a) Pagenkopf, B. L.; Belanger,
D. B.; O’Mahony, D. J. R.; Livinghouse, T. Synthesis
2000, 1009–1019; (b) Oh, C. H.; Jung, S. H.; Rhim, C. Y.
Tetrahedron Lett. 2001, 42, 8669–8671.
1
1
1
J. Organomet. Chem. 2001, 624, 73–87.
2
16. [RhCl(CO)dppp] was shown to be fruitless in the trans-
1
1. For reviews on cycloisomerization of enynes, see: (a)
Trost, B. M. Acc. Chem. Res. 1990, 23, 34–42; (b) Aubert,
C.; Buisine, O.; Malacria, M. Chem. Rev. 2002, 102, 813–
formation of 3d into 5d.
17. Formation of fused cyclobutenes from allenynes has been
reported. For transition metal-mediated cycloadditions,
see: Shen, Q.; Hammond, G. B. J. Am. Chem. Soc. 2002,
124, 6534–6535; For thermal cyclizations, see: Cao, H.;
Flippen-Anderson, J.; Cook, J. M. J. Am. Chem. Soc.
2003, 125, 3230–3231.
8
2. For Rh(I)-catalyzed enyne cycloisomerization, see: Cao,
34.
1
P.; Wang, B.; Zhang, X. J. Am. Chem. Soc. 2000, 122,
490–6491.
6
1
3. For Rh(I)-catalyzed allenene cycloisomerization, see: Mak-
ino, T.; Itoh, K. Tetrahedron Lett. 2003, 44, 6335–6338.
4. During this on-going study, a similar Rh(I)-catalyzed
allenyne cycloisomerization has been reported indepen-
dently by two groups. Brummond et al. have reported the
18. Formation of the bicyclo[5.2.0]nonene skeleton via ther-
molysis of 2-azetidinone-tethered enallenes has been
reported: Alcaide, B.; Almendros, P.; Aragoncillo, C.
Org. Lett. 2003, 5, 3795–3798.
1
2 2
19. Reaction of 5e in the presence of [RhCl(CO) ] for 9 h
[
RhCl(CO)
2
]
2
-catalyzed construction of six-membered tri-
provided 6e in 60% yield, along with recovered 5e (11%),
whereas only 42% yield of 6e and 10% of the recovered
5e were obtained in the absence of Rh(I) catalyst for
9 h.
ene derivatives: Brummond, K. M.; Chen, H.; Sill, P.;
You, L. J. Am. Chem. Soc. 2002, 124, 15186–15187; An
example of the preparation of seven-membered oxacycle
with triene moiety using a RhCl(PPh
3
)
3
-catalyzed reac-
20. Refluxing 3f in xylene resulted in decomposition.
21. Allenyne having TMS group at the alkyne terminus
afforded the corresponding bicyclo[5.2.0]nonene derivative
in 34% yield.
tion, developed by Shibata et al., has also been reported.
Shibata, T.; Takesue, Y.; Kadowaki, S.; Takagi, K.
Synlett 2003, 268–270.