Preparation of substituted cyclopentadienes through platinum(II)-catalyzed cyclization of 1,2,4-trienes

Article abstract of DOI:10.1002/anie.200603986

(Chemical Equation Presented) A pinch of platinum... Platinum(II)-catalyzed cyclization of 1,2,4-trienes proceeds under mild conditions to give well-defined, highly substituted cyclopentadienes in good yield. The reaction was confirmed to proceed through

Full text of DOI:10.1002/anie.200603986

Angewandte
Chemie
DOI: 10.1002/anie.200603986
Cyclopentadiene Synthesis
Preparation of Substituted Cyclopentadienes through Platinum(II)-
Catalyzed Cyclization of 1,2,4-Trienes**
Hideaki Funami, Hiroyuki Kusama, and Nobuharu Iwasawa*
Table 1: Cyclization of 1,2,4-triene 1a to give cyclopentadiene 2a.
Cyclopentadienes (Cps) are highly useful synthetic inter-
mediates in the field of organic and organometallic chemistry.
They are useful not only as a reactive diene component in the
Diels–Alder reaction[1] but also as a precursor for the
preparation of transition-metal complexes with Cp-type
ligands.[2] However, the preparation of well-defined, highly
substituted cyclopentadienes is not necessarily easy owing to
the absence of general methods[3] and also to the facile
migration of the endocyclic double bonds.[4] Herein we
describe a novel method for the preparation of highly
substituted cyclopentadiene derivatives based on the PtII-
catalyzed cyclization of 1,2,4-trienes in which platinum–
carbene intermediates play an important role in determining
the reaction pathways.
We expected that treatment of 1,2,4-trienes with appro-
priate electrophilic transition-metal complexes[5] would gen-
erate a,b-unsaturated carbene complexes III through cycliza-
tion of p complex I[6] and/or pentadienyl cationic complex II,
and that the produced carbene complex III would further
undergo useful transformations to give cyclopentadienes or
their derivatives [Eq. (1)].
Entry
Catalyst
Solvent
t [h]
Yield [%][a]
1[b]
2
3
4
5
[W(CO)6]
PtCl2
PtCl2
PtCl2
PtCl2
PtCl4
AuCl3
PdCl2
[IrCl(cod)]2
CF3SO3H
THF
toluene
THF
CH3CN
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
10
24
48
48
19
20
20
48
48
48
0
66
0
0
86
43[c]
60[c]
0
0
0
6
7
8
9[d]
10
[a] Yield of the isolated product. [b] The reaction was performed in the
presence of 0.1 equivalents of [W(CO)6] under direct photoirradiation.
[c] The yields were determined by NMR spectroscopy by comparison
with an internal standard (dibromomethane). [d] The reaction was
performed in the presence of 0.025 equivalents of [IrCl(cod)]2 (cod=
cycloocta-1,5-diene).
also showed considerable catalytic activity (Table 1, entries 6
and 7), whereas PdCl2 and [IrCl(cod)]2 did not (Table 1,
entries 8 and 9). It was also noted that the reaction with protic
acids such as CF3SO3H did not yield any cyclopentadiene 2a
(Table 1, entry 10).
On the basis of these considerations, we initiated our
study to find optimal conditions for this reaction using 5-
(cyclohex-1-enyl)-1-phenylhepta-3,4-diene (1a) as a sub-
strate, with a catalytic amount of various electrophilic
transition-metal complexes. The expected cyclization of 1a
We then investigated the generality of the reaction using
various 1,2,4-trienes (Table 2).[9] Various alkyl groups were
used as R2 in triene 1, and the corresponding cyclopenta-
Table 2: Platinum(II)-catalyzed cyclization of 1,2,4-trienes 1 to afford
cyclopentadienes 2.
[7,8]
proceeded most effectively with 0.05 equivalents of PtCl2
in dichloroethane at room temperature, and the correspond-
ing cyclopentadiene 2a was obtained in 86% yield with about
95% regioisomeric purity concerning the double bonds
(Table 1, entry 5). Other catalysts such as PtCl4 and AuCl3
Entry
R1
R2
R3
R4
t [h] Yield [%][a]
[*] H. Funami, Dr. H. Kusama, Prof. Dr. N. Iwasawa
Department of Chemistry
(product)
1
2
3
4
5
6
7
8
9
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
Ph(CH2)2
iPr
Et
nBu
Bn
CH2 CH(CH2)2
AcO(CH2)5
-(CH2)4-
19
24
64
54
48
44
48
23
60
86 (2a)
80 (2b)
81 (2c)
54 (2d)
88 (2e)
85 (2 f)
77 (2g)
77 (2h)
86 (2i)
Tokyo Institute of Technology
2-12-1-E1-2, O-okayama
Meguro-ku, Tokyo 152-8551 (Japan)
Fax: (+81)3-5734-2931
E-mail: niwasawa@chem.titech.ac.jp
-(CH2)4-
-(CH2)4-
-(CH2)4-
-(CH2)4-
=
Et
Me
Me
H
H
[**] This research was partly supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science,
and Technology of Japan. H.F. was granted a Research Fellowship of
the Japan Society for the Promotion of Science for Young Scientists.
Bn
nBu
Bn
-(CH2)4-
Me
iPr
H
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
[a] Yield of the isolated product. Note that a small amount of double-
bond regioisomers (ꢀ5%) was found in most cases. Bn=benzyl.
Angew. Chem. Int. Ed. 2007, 46, 909 –911
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909

Communications
dienes were obtained in high yield (Table 2, entries 1–3).
Even 1,2,4-trienes containing a vinyl group (1d) or an ester
moiety (1e) could be employed to give the corresponding
We next applied this cyclization reaction to 1,1-disubsti-
tuted 1,2,4-trienes. When 1,2,4-triene 3 was treated with
0.1 equivalents of PtCl2 in dichloroethane at room temper-
ature, a ring-enlargement reaction proceeded smoothly to
give the pentasubstituted cyclopentadiene 4 in 79% yield
(Scheme 3).[12] The platinum–carbene intermediate C was
thought to undergo 1,2-alkyl migration[13] to give 4, and
tetrasubstituted cyclopentadienes
2 in reasonable yield
(Table 2, entries 4 and 5). Furthermore, trisubstituted cyclo-
pentadienes 2 f, 2g, and 2i with R4 = H could be obtained
from 1,2,4-trienes 1 f, 1g, and 1i, respectively, in high yields
(Table 2, entries 6, 7, and 9). Note that in all cases the
cyclopentadienes 2 were mostly obtained as a single regio-
isomer about the double bonds owing to the mildness of the
reaction conditions.
A plausible mechanism for this PtCl2-catalyzed cyclization
of 1,2,4-trienes is shown in Scheme 1. Intermediates A,
generated by complexation of 1,2,4-triene 1 with platinu-
Scheme 3. Platinum(II)-catalyzed tandem cyclization/ring-expansion
reaction of 1,2,4-triene 3 to give pentasubstituted cyclopentadiene 4.
almost no double-bond isomerization was observed in this
case also.
Direct evidence of the presence of the carbene inter-
mediate was obtained by the reaction of 1,1-dimethyl-1,2,4-
triene 5. Treatment of this substrate with 0.1 equivalents of
PtCl2 at 508C gave a tricyclic cyclopropane 6 in 72% yield
(Scheme 4). The cyclized product 6 was obtained as a mixture
of two stereoisomers (6a/6b = 3:1), the structures of which
Scheme 1. Proposed reaction mechanism of the platinum(II)-catalyzed
cyclization of 1,2,4-trienes.
m(II), are converted into a,b-unsaturated car-
bene complexes
B through intramolecular
nucleophilic attack of the olefinic double bond
on the PtCl2-p-complexed allenic double
bond[10] and/or Nazarov-type 4p electrocycliza-
tion of pentadienyl cationic complexes.[11] The
platinum–carbene intermediate B then under-
À
Scheme 4. Platinum(II)-catalyzed tandem cyclization/C H insertion reaction of 1,2,4-
goes a 1,2-hydrogen shift to give the product 2 triene 5 to give cyclopropane 6.
with regeneration of the platinum catalyst.
To examine this proposed reaction mecha-
nism, we carried out
(Scheme 2). When deuterated substrate [D]-1j was subjected
to the same reaction conditions, cyclopentadiene [D]-2j with
a
deuterium-labeling experiment
were confirmed by measurement of various 1D and 2D NMR
spectra (Scheme 4).[14] In this case, the platinum–carbene
intermediate D inserted into the neighboring carbon–hydro-
gen bond of the methyl group[15] rather than undergoing 1,2-
methyl migration. Formation of the cyclopropane 6 clearly
proved the presence of the platinum–carbene intermediate
D.[13,16]
In conclusion, we have developed a PtCl2-catalyzed
preparation of highly substituted cyclopentadiene derivatives
from 1,2,4-trienes. This reaction proceeds under mild con-
ditions to afford a variety of well-defined, highly substituted
cyclopentadienes, which are key intermediates in organic
synthesis and useful ligands in organometallic chemistry.
Furthermore, we have succeeded in confirming the presence
of a,b-unsaturated platinum–carbene complexes as inter-
mediates by applying this protocol to the tandem cyclization/
Scheme 2. Deuterium-labeling experiment.
the deuterium label at the vinylic position (> 95% D
incorporation) was obtained in 92% yield. This result is
consistent with the 1,2-hydrogen migration of the carbene
complex intermediate.
À
ring expansion reaction and the tandem cyclization/C H
insertion reaction.
910
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[8] For recent reviews on platinum(II)-catalyzed reactions, see:
Experimental Section
a) M. MØndez, V. Mamane, A. Fürstner, Chemtracts 2003, 16,
397 – 425; b) A. M. Echavarren, C. Nevado, Chem. Soc. Rev.
2004, 33, 431 – 436.
Typical procedure: Platinum(II) chloride (2.7 mg, 0.01 mmol) was
added to a mixture of 1,2,4-triene 1a (50.5 mg, 0.2 mmol) and 4-Š
molecular sieves (200 mg) in 1,2-dichloroethane (2.0 mL) at room
temperature. After disappearance of the starting material was
confirmed by TLC, the reaction mixture was filtered through Celite
using diethyl ether as eluent. The filtrate was washed with an aqueous
saturated solution of NaHCO3 and then brine, dried over MgSO4, and
filtered. The resulting filtrate was concentrated under reduced
pressure, and the residue was purified by preparative TLC (hexane)
to give the cyclopentadiene 2a (43.3 mg, 0.17 mmol) in 86% yield as a
colorless oil.
[9] 1,2,4-Trienes 1 were readily prepared in three steps [Eq. (2);
Ms = methanesulfonyl]. See Supporting Information for details.
Received: September 28, 2006
Published online: December 19, 2006
Keywords: allenes · carbenes · cyclopentadienes · platinum ·
synthetic methods
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[14] The presence of the cyclopropane ring was confirmed mainly on
the basis of the presence of geminal protons in a highfield region
(d = À0.1–0.6 ppm) with a small geminal coupling constant (J =
3.2 Hz), features that are characteristic of cyclopropane deriv-
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differential NOE spectra. See Supporting Information for details
of the assignment.
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