Complexation-initiated intramolecular [4+2] cycloaddition: Construction of bridged-type cycloadducts

Article abstract of DOI:10.1002/anie.200502313

(Chemical Equation Presented) The characteristic structural features of [(alkyne)Co₂(CO)₆] complexes were used to achieve bridged-type intramolecular [4 + 2] cycloaddition reactions. The reaction of such complexes bearing a siloxydie

Full text of DOI:10.1002/anie.200502313

Angewandte
Chemie
Cycloadditions
DOI: 10.1002/anie.200502313
Complexation-Initiated Intramolecular
[4+2] Cycloaddition: Construction of
Bridged-Type Cycloadducts**
Nobuharu Iwasawa,* Kennichi Inaba,
Satoko Nakayama, and Masao Aoki
Intramolecular cycloaddition reactions of linear substrates
generally give fused-type adducts selectively, owing to the
favorable straight alignment of the two reacting sites
(Scheme 1). There have been many examples of fused-type
Scheme 1. The regioselectivity in the intramolecular [4+2] cycloaddi-
tion reaction.
intramolecular Diels–Alder reactions, but very few are known
for the corresponding bridged-type Diels–Alder reaction.[1,2]
Even in these cases, the bridged-type adducts were obtained
as minor products along with the major fused-type prod-
ucts.[3,4]
We previously reported that alkynes bearing a furan diene
and a dienophile unit on opposite ends, when complexed with
[Co2(CO)8], shift from a straight structure to a bent one (that
is, the angle changes from 1808 to around 1408). A subsequent
intramolecular Diels–Alder reaction provides a mixture of
the starting alkyne–Co2(CO)6 complex and the desired
cyclized alkyne–Co2(CO)6 complex in equilibrium.[5] The
important feature of this reaction is the ready formation of
a seven-membered ring by the carbon tether. This is probably
due to the rigid and planar structure of the alkyne–Co2(CO)6
moiety, compelling the two substituents at the alkyne to form
an angle of about 1408,[6] which facilitates formation of the
seven-membered ring.[7] We expected that this structural
[*] Prof. Dr. N. Iwasawa, K. Inaba, S. Nakayama, Dr. M. Aoki
Department of Chemistry
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
[**] This research was partly supportedby a Grant-in-Aidfor Scientific
Research from the Ministry of Education, Culture, Sports, Science,
andTechnology of Japan. We are grateful to the Tosoh Finechem
Corporation for a generous gift of MeAlCl2.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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feature of the alkyne–Co2(CO)6 moiety—namely, the wider
adduct was confirmed by X-ray crystal structure analysis of
the corresponding hydrolyzed ketone.[10] This result proves
that the cycloaddition is not a concerted Diels–Alder
angle of alkyne substituents compared to alkene substitu-
ents—might lessen the steric congestion in the transition state
and allow formation of the bridged-type adduct. Thus, by the
appropriate design of substrates in which orbital or electronic
control favors the formation of bridged-type products, we
could carry out a bridged-type cycloaddition reaction selec-
tively, even with simple linear substrates. Here we describe
the successful development of this novel bridged-type [4+2]
cycloaddition reaction of silyloxydiene derivatives[8] utilizing
alkyne–Co2(CO)6 complex formation.
reaction, but
a stepwise, double-Michael-type reaction
giving the bridged-type [4+2]-cycloadduct.[11]
To prevent hydrolysis, we further examined the reaction in
the presence of 2,6-di-tert-butylpyridine (DTBP), which is a
well-known proton scavenger.[12] When the reaction was
carried out employing 2 equivalents of MeAlCl2 in the
presence of 0.1 equivalents of DTBP in CH2Cl2 at À788C,
formation of the hydrolyzed products was efficiently sup-
pressed and the desired product 2 was obtained in 75% yield
(Table 1, entry 5).
First, the reaction was examined using the alkyne–
Co2(CO)6 complex 1, which contains a silyloxydiene and an
electron-deficient dienophile [Eq. (1); TBS = tert-butyldi-
We then extended the scope of the reaction using several
substrates. As shown in Equation (2), the same type of
methylsilyl]. When the reaction was carried out in the
presence of 2 equivalents of BF3·OEt2 in CH2Cl2 at À788C,
the desired [4+2]-cycloadduct was not obtained; instead 4,
the hydrolyzed product of the starting material, was isolated
in 34% yield (Table 1, entry 1). In contrast, when AlCl3 was
substrates 5 and 6 gave the corresponding bridged-type [4+2]
cycloadducts in good yield as a single stereoisomer when the
reaction was carried with 2 equivalents of MeAlCl2 in the
presence of 0.1–0.3 equivalents of DTBP in CH2Cl2 at À788C.
For the reaction with substrate 6, the [4+2]-cycloadduct 8 was
accompanied by a small amount of its hydrolyzed cycloadduct
9. The configuration of the products were determined based
on the analogy of the coupling pattern of their 1H NMR
spectra with that of 2.
The reaction of substrate 10, having an additional carbon
atom in the tether, also gave the desired bridged-type adduct
11 with a bicyclo[6.3.1]dodec-3-yn-2-one skeleton as a single
stereoisomer in reasonable yield [Eq. (3)]. The structure was
again confirmed by X-ray crystal structure analysis of the
corresponding hydrolyzed ketone.[10] Furthermore, the reac-
Table 1: Results of the intramolecular [4+2]-cycloaddition reaction in the
presence of a Lewis acid[see Eq. (1)].
Entry
Lewis acid
t [h]
2 [%]
3 [%]
4 [%]
1
BF3·OEt2
AlCl3
Et2AlCl
MeAlCl2
MeAlCl2
0.5
25
3.5
3.0
0
34
27
40
75
0
12
0
30
1
34
26
0
17
2
2[a]
3
4[a]
5[a,b]
0.33
[a] Products 3 and 4 were obtainedas an inseparable mixture. The yields
were determined by 1H NMR spectroscopy. [b] For this reaction
0.1 equivalent of DTBP was added.
employed as a Lewis acid, the starting material disappeared at
À788C, and the cycloadduct was isolated in 34% yield along
with the Michael-type adduct 3 and the hydrolyzed ketone 4
in 12% and 26% yields, respectively (entry 2). Among
several aluminum-containing Lewis acids examined,
MeAlCl2 gave the best results (entry 4).[9]
Analysis of the NMR spectra of the cycloadduct obtained
demonstrated that the product was not a normal fused-type
adduct, but rather the bridged-type adduct 2 having a
bicyclo[5.3.1]undec-3-yn-2-one skeleton. The product was
isolated as a single stereoisomer, and the structure of the
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Table 3: Results of the demetalation reaction of bridged-type alkyne–Co2(CO)6 cycloadducts.[a]
tion of substrate 12, which has one less
carbon atom in the tether than 1, also
proceeded albeit in moderate yield, prob-
ably due to the severe strain of the system.
The desired adduct 13, with the bicyclo-
Entry Substrate
Reaction conditions
Product
Yield [%]
68
1
Et3SiH, BTMSA, DCE, 658C, 6.5 h
[4.3.1]dec-3-yn-2-one
skeleton,
was
obtained in 39% yield by carrying out the
reaction with 5.25 equivalents of MeAlCl2
in CH2Cl2 at room temperature [Eq. (4)].[13]
Thus, this bridged-type [4 + 2] cycloaddition
reaction shows reasonable generality with
respect to the substituents and the number
of carbon atoms in the tether.
2
3
4
Et3SiH, BTMSA, DCE, 658C, 24 h
77
72
66
We then examined the reaction of the
NaH2PO2·H2O, 2-methoxyethanol,
658C, 2 h
corresponding olefinic substrate 14 to con-
firm the importance of the alkyne–
Co2(CO)6 moiety for the formation of the
bridged-type products. The vinylsilane sub-
strate 14 was obtained in 63% yield by
reduction of 5 with triethylsilane.[14] Treat-
ment of 14 under several typical cycloaddi-
tion reaction conditions did not give the
corresponding bridged-type cycloadduct,
but instead the monocyclic Michael addi-
tion products 15 and 16 in high yield
[Eq. (5), Table 2]. We believe that the wider bent angle of
the alkyne–Co2(CO)6 complexes releases the steric conges-
H2O, toluene, reflux, 2 h
[a] BTMSA=bis(trimethylsilyl)acetylene, DCE=1,2-dichloroethane.
Co2(CO)6 moiety to give vinylsilanes 18a and 19a in good
yields upon heating of the complexes in the presence of
triethylsilane (entries 1 and 2).[15] Furthermore, the reaction
of 17 with sodium hypophosphite[16] proceeded smoothly to
give enone 19b (entry 3), while the same reaction using silyl
enol ether 2 resulted in a complex mixture of products. To our
surprise, simple heating of complex 2 in toluene/H2O (5/1)
with vigorous stirring gave the desired decomplexed enone
18b in good yield without hydrolyzing the silyl enol ether
moiety (entry 4). Although details of this demetalation
reaction remain to be explored, this method affords a
simple conversion of alkyne–Co2(CO)6 complexes into the
corresponding alkenes.[17]
In conclusion, we have developed a method for the
preparation of bridged-type [4+2]-cycloadducts utilizing
alkyne–Co2(CO)6 complex formation. Synthetically useful
bicyclo[n.3.1] skeletons with multiple functionalities could be
prepared stereoselectively by this procedure.
Table 2: Results of the reactions with the olefinic substrate 14 [see
Eq. (5)].
Entry
T
t [min]
15 [%]
16 [%]
1
À788C
À788C
RT
115
50
10
65
45
trace
33
44
80
2[a]
3
Experimental Section
Cyclization of 1: The alkyne–cobalt complex 1 was purified by PTLC
(hexane/CH2Cl2 1/1) just before use. 2,6-Di-tert-butylpyridine
[a] DTBP was not added.
(4.20 mL, 18.4 mmol) was added to
a solution of 1 (125 mg,
tion of the transition state and enables the smooth formation
of the bridged-type cycloadduct. However, further examina-
tion is necessary to clarify the exact role of the alkyne–
Co2(CO)6 moiety.
Finally, we investigated the decomplexation of the
alkyne–Co2(CO)6 moiety from the bridged-type cycloadducts
(Table 3). The cycloadduct 2 and its hydrolyzed ketone 17
both underwent smooth hydrosilylation of the alkyne–
0.187 mmol) in CH2Cl2 (19 mL) at À788C. After 5 min a solution of
MeAlCl2 (0.370 mL, 0.370 mmol) in hexane (1.0m) was added, and
the mixture was stirred for 20 min at À788C. Then the reaction was
quenched with saturate aqueous NaHCO3, and the product was
extracted with ethyl acetate three times. The combined organic
extracts were washed with brine, dried over anhydrous sodium
sulfate, filtered, and concentrated under reduced pressure. The
residue was purified by PTLC (hexane/CH2Cl2 1/1) to give 2
(93.0 mg, 0.140 mmol) in 75% yield as a dark red oil. Compounds 3
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and 4 were obtained as an inseparable mixture in a 1:2 ratio (3.10 mg,
5.60 mmol) in 3% yield as a dark red oil.
[17] This demetalation reaction is general for medium-sized cyclic
alkynone–Co2(CO)6 complexes. A [HCo(CO)3(L)] species, gen-
erated by decomposition of the alkyne–Co2(CO)6 complex,
might be acting as a reductant; see R. W. Goetz, M. Orchin, J.
Org. Chem. 1962, 27, 3698.
Received: July 2, 2005
Published online: October 20, 2005
Keywords: alkyne ligands · cobalt · cycloaddition ·
.
demetalation
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[8] A related intramolecular Diels–Alder reaction of a siloxydiene
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[10] CCDC-276360 (for adduct 2) and CCDC-276361 (for adduct 11)
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
[11] There have been no reports on bridged-type intramolecular
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[12] P. V. Bonnesen, C. L. Puckett, R. V. Honeychuck, W. H. Hersh,
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[13] Product 13 was obtained as a single stereoisomer; the relative
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[14] S. Hosokawa, M. Isobe, Tetrahedron Lett. 1998, 39, 2609 – 2612.
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