Platinum(II)-catalyzed reaction of γ,δ-ynones with alkenes for the construction of 8-oxabicyclo[3.2.1]octane skeletons: Generation of platinum-containing carbonyl ylides from acyclic precursors

Article abstract of DOI:10.1002/anie.200705129

(Chemical Equation Presented) Two types of bicycles can be prepared selectively by the title reaction, depending on whether or not a substituent is present at the propargylic position of the ynone substrate (see scheme). The cycloaddition of carbonyl ylid

Full text of DOI:10.1002/anie.200705129

Angewandte
Chemie
DOI: 10.1002/anie.200705129
Cycloaddition
Platinum(II)-Catalyzed Reaction of g,d-Ynones with Alkenes for the
Construction of 8-Oxabicyclo[3.2.1]octane Skeletons: Generation of
Platinum-Containing Carbonyl Ylides from Acyclic Precursors**
Hiroyuki Kusama, Kento Ishida, Hideaki Funami, and Nobuharu Iwasawa*
Transition-metal-containing zwitterionic intermediates gen-
erated through the electrophilic activation of alkynes toward
nucleophilic attack by a carbonyl oxygen atom or imino
nitrogen atom can be used in addition reactions with
nucleophiles or cycloaddition reactions with alkenes or
alkynes to prepare synthetically useful heterocyclic com-
pounds.[1–5] However, in almost all cases, it is necessary to
employ rigid aromatic substrates for the effective generation
of the zwitterionic species. Herein, we report a catalytic
method for the generation of nonconjugated platinum(II)-
containing carbonyl ylides from acyclic g,d-ynones and the
Scheme 1. Generation and reaction of the platinum-containing
carbonyl ylide 3a derived from the acyclic g,d-ynone 1a.
[3+2]cycloaddition of such ylides with electron-rich alkenes
to give synthetically useful 8-oxabicyclo[3.2.1]octane deriva-
tives in good yield.
First, we examined the reaction of the acyclic g,d-ynone
1a, which contains a methyl substituent at the propargylic
position, with n-butyl vinyl ether in the presence of a catalytic
amount of various electrophilic transition-metal complexes.
Although several typical complexes, such as [W(CO)5(thf)],
[ReCl(CO)5]/hn, [{IrCl(cod)}2], AuCl3, and [AuClPPh3]/
AgSbF6, caused either no reaction or hydration of the
Examination of the reaction with several electron-rich
alkenes revealed that unsubstituted vinyl ethers, such as
p-methoxybenzyl vinyl ether, could be used as cycloaddition
partners (Table 1, entry 1). Furthermore, the desired product
Table 1: Reaction of various acyclic g,d-ynones that contain a substituent
at the propargylic position.
[6]
alkyne moiety, PtCl2 was found to be very effective. Thus,
the treatment of 1a with platinum(II) chloride (10 mol%) in
the presence of n-butyl vinyl ether at room temperature gave
the 8-oxabicyclo[3.2.1]octane derivative 2a in 78% yield as a
single diastereoisomer with the butoxy substituent in an exo
orientation.
1
EntryR
R2
R3
R4
t
Yield [%]
We propose the following mechanism for the formation of
2a: The electrophilic activation of the alkyne moiety in 1a by
platinum(II) chloride induces the attack of the carbonyl
oxygen atom onto the alkyne in a 6-endo manner to generate
the platinum-containing carbonyl ylide 3a, which then under-
goes a [3+2]cycloaddition reaction with n-butyl vinyl ether to
give the nonstabilized carbene complex 4a. Finally, a
1,2-hydrogen-atom shift to the carbene carbon atom gives
the product 2a with regeneration of the catalyst (Scheme 1).
1
2
3
4
Ph
Ph
Ph
Et
Me
Me
EtO
Me
Me
Me
Me
n-pentyl
OPMB
Ph
nBuO
nBuO
27 h
5 days
8 h
76
43
84
77
5 days
was formed in moderate yield when styrene was used
(Table 1, entry 2). Acyclic g,d-ynones with an alkyl or
alkoxy group at the propargylic position were used success-
fully as substrates to give synthetically useful 8-oxabicyclo-
[3.2.1]octane derivatives in good yield (Table 1, entries 3 and
4). The cyclohexane derivative 5 also underwent the desired
transformation with n-butyl vinyl ether to give the tricyclic
compound 6 in 76% yield (Scheme 2). In all cases, the
reaction afforded the corresponding exo product stereoselec-
tively.
The use of g,d-ynone substrates 7 with no substituent at
the propargylic position led to interesting results. The
reaction of 7a with n-butyl vinyl ether under the reaction
conditions used for the transformation of ynones 1 proceeded
smoothly at room temperature. However, careful analysis of
[*] Dr. H. Kusama, K. Ishida, Dr. H. Funami, Prof. Dr. N. Iwasawa
Department of Chemistry
Tokyo Institute of Technology
O-okayama, Meguro-ku, Tokyo 152-8551 (Japan)
Fax: (+81)3-5734-2931
E-mail: niwasawa@chem.titech.ac.jp
[**] This research was partlysupported bya Grant-in-Aid for Scientific
Research from the Ministryof Education, Culture, Sports, Science,
and Technologyof Japan. H.F. was granted a Research Fellowship of
the Japan Societyfor the Promotion of Science for Young Scientists.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200705129.
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Communications
Table 2: Reaction of various acyclic g,d-ynones with no substituent at the
propargylic position.
Scheme 2. Reaction of the cyclohexane derivative 5.
1
EntryR
R2
R3
R4
R5
t
Yield [%]
the products obtained revealed that the major product was
the 8-oxabicyclo[3.2.1]octane derivative 8a, rather than 9a,
which might have been expected to form as the major product
on the basis of the results observed with ynones 1. Compound
9a was obtained as a minor product (Scheme 3).
1
2
3
Ph
Ph
Ph
Ph(CH2)2
Ph
H
H
H
H
Me
CO2Et
H
H
H
H
Me
Me
OEt
OPMB 31 h
39 h
68
84
nBu nBuO
Me
5 days 67
4[a]
5[b]
6[c]
nBuO
nBuO
nBuO
4 days 55
4 days 52
6 days 55
Me Me
Me
Ph
H
[a] [PtCl2(CH2CH2)]2 (5 mol%) was used as the catalyst. [b] The product
was obtained as a ketone. [c] PtCl2: 30 mol%.
Scheme 4. Intramolecular reaction.
Scheme 3. Platinum-catalyzed reaction of acyclic g,d-ynones with no
substituent at the propargylic position.
In conclusion, we have demonstrated the generation of
bifunctional reactive species, platinum(II)-containing
carbonyl ylides, from acyclic g,d-ynones and the reaction of
these intermediates with electron-rich olefins to give syntheti-
cally useful 8-oxabicyclo[3.2.1]octane derivatives.[10] The
presence or absence of a substituent at the propargylic
position of the ynone substrate determines the course of the
reaction after the formation of an intermediate carbene
complex, so that two types of 8-oxabicyclo[3.2.1]octane
derivatives can be formed selectively.
The formation of this new type of product 8a could be
explained as follows (Scheme 3): The nonstabilized inter-
mediate carbene complex 10a is produced from 7a in a
similar manner to the formation of 4a from 1a. Instead of the
1,2-hydrogen-atom shift observed for substrates with a
substituent at the propargylic position, 10a undergoes
1,2-alkyl migration[1c,f,h,2k,7] to generate the oxonium inter-
mediate 11a.[8] A further alkyl-group migration to the
oxonium moiety produces another nonstabilized carbene
intermediate 12a, which undergoes a 1,2-hydrogen-atom shift
to give product 8a.[9]
Experimental Section
General procedure: An alkene (0.5–1.0 mmol) was added to a
mixture of an acyclic g,d-ynone (0.1 mmol), PtCl2 (0.01 mmol), and
molecular sieves (4 Š; 100 mg) in toluene (1.0 mL) at room temper-
ature, and the resulting mixture was stirred at room temperature until
TLC showed the complete disappearance of the g,d-ynone. The
reaction was then quenched with saturated, aqueous NaHCO3, and
the reaction mixture was filtered through a short pad of celite. The
aqueous layer was extracted with ethyl acetate three times, and the
combined organic layers were washed with brine, then dried over
MgSO4. The solvent was removed under reduced pressure, and the
residue was purified by chromatography on silica gel to afford the
corresponding 8-oxabicyclo[3.2.1]octane derivative.
The generality of the reaction of this type of substrate is
summarized in Table 2. 8-Oxabicyclo[3.2.1]octane derivatives
8 were obtained as the major product in all reactions of acyclic
g,d-ynones with no substituent at the propargylic position.
Even an active-methyne compound underwent this reaction
to give the desired 8-oxabicyclo[3.2.1]octane derivative in
good yield (Table 2, entry 6).
Finally, we attempted an intramolecular version of this
reaction. Thus, treatment of the acyclic g,d-ynone 13, which
contains a styrene moiety, with a catalytic amount of
platinum(II) chloride gave the desired product of intra-
molecular cyclization, the useful polycyclic compound 14, in
good yield (Scheme 4).
Received: November 7, 2007
Published online: May 21, 2008
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Angewandte
Chemie
Chem. Lett. 2006, 35, 1082 – 1087; b) N. Asao, Synlett 2006,
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Keywords: carbene ligands · carbonyl ylides · cycloaddition ·
platinum · ynones
.
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a platinum-containing zwitterionic intermediate 3 with
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