An Intramolecular Allenic [2 + 2 + 1] Cycloaddition

Article abstract of DOI:10.1021/jo980548c

A new stereo- and regioselective method for the preparation of α-methylene and 4-alkylidene cyclopentenones is described. These substructures were achieved by an intramolecular [2 + 2 + 1] cycloaddition of an allene, alkyne, and carbon monoxide moieties to afford the target compounds stereoselectively and in good yields. In some cases, the target compounds were obtained as mixtures, but it is demonstrated that the formation of either the α-methylene or 4-alkylidene cyclopentenone can be controlled by the allene structure or reaction conditions. Monosubstituted allenes afford α-methylene cyclopentenones as the only cycloadduct. Disubstitution on the allene alters the course of the allenic [2 + 2 + 1] reaction. 3,3-Disubstituted allenes undergo cycloaddition with the least substituted π-bond of the allene. This affords the bicyclo[4.3.0]nonane ring system. Cycloaddition of 1,3-disubstituted allenes afford mixtures of several possible cycloadducts. However, it has been shown that good control over the product ratio can be obtained by altering the cycloaddition conditions and that the regiochemistry can be directed depending upon the metal used.

Full text of DOI:10.1021/jo980548c

J . Org. Chem. 1998, 63, 6535-6545
6535
An In tr a m olecu la r Allen ic [2 + 2 + 1] Cycloa d d ition
Kay M. Brummond,* Honghe Wan, and J oseph L. Kent†
Department of Chemistry, West Virginia University, Morgantown, West Virginia 26506
Received March 24, 1998
A new stereo- and regioselective method for the preparation of R-methylene and 4-alkylidene
cyclopentenones is described. These substructures were achieved by an intramolecular [2 + 2 +
1] cycloaddition of an allene, alkyne, and carbon monoxide moieties to afford the target compounds
stereoselectively and in good yields. In some cases, the target compounds were obtained as mixtures,
but it is demonstrated that the formation of either the R-methylene or 4-alkylidene cyclopentenone
can be controlled by the allene structure or reaction conditions. Monosubstituted allenes afford
R-methylene cyclopentenones as the only cycloadduct. Disubstitution on the allene alters the course
of the allenic [2 + 2 + 1] reaction. 3,3-Disubstituted allenes undergo cycloaddition with the least
substituted π-bond of the allene. This affords the bicyclo[4.3.0]nonane ring system. Cycloaddition
of 1,3-disubstituted allenes afford mixtures of several possible cycloadducts. However, it has been
shown that good control over the product ratio can be obtained by altering the cycloaddition
conditions and that the regiochemistry can be directed depending upon the metal used.
Sch em e 1
In tr od u ction
Since the discovery of the Pauson-Khand (P-K)
reaction (formally a [2 + 2 + 1] cycloaddition) in the early
1970’s,1 a great deal of work has transpired to increase
the synthetic value of this method and is now regarded
as a method of choice when preparing cyclopentenones.2
Curiously at the initiation of this research, no successful
examples of using allenes in place of the olefin component
in this [2 + 2 + 1] cycloaddition had been reported.3 We
felt this would be an interesting process to investigate
since there are two π-bonds with which the cyclization
process can occur (Scheme 1). If this reaction occurs with
the internal π-bond (reaction pathway A), the resulting
cycloadduct will be an R-methylene cyclopentenone. If
the reaction occurs with the external π-bond of the allene
(reaction pathway B), the resulting adduct will be a
4-alkylidene cyclopentenone. Either cyclization pathway
gives interesting substructures which are present in a
variety of biologically important compounds such as the
illudins4 and the prostaglandins.5
shown in Scheme 2. Addition of lithium (trimethylsilyl)-
acetylide to 1,3-dibromopropane followed by treatment
of the resulting bromoalkyne with magnesium, copper
bromide, and propargyl methyl ether afforded the desired
alkynyl allene 1. All attempts to effect a Pauson-Khand
type cycloaddition of compound 1 using dicobalt octac-
arbonyl [Co2(CO)8] were unsuccessful.6 However, use of
conditions reported by J eong and co-workers7 proved to
be quite successful in the formation of R-methylene
cyclopentenone 2. Treatment of alkynyl allene 1 with
molybdenum hexacarbonyl [Mo(CO)6] and dimethyl sul-
foxide at 100 °C gave compound 2 in a 68% yield. The
1H NMR spectrum showed new resonances at δ 5.92 and
5.27 characteristic of the exocyclic methylene protons and
a new absorption appeared at 1692 cm-1 in the IR
inferring an unsaturated cyclic ketone. The reaction can
be monitored reliably by GC-MS, and the color of the
reaction media has also proven to be diagnostic of the
progress of the reaction. As the reaction temperature
approaches 100 °C the molybdenum dissolves and the
clear heterogeneous mixture turns bright yellow and
Resu lts a n d Discu ssion
Mon osu bstitu ted Allen es. The feasibility of this
allenic [2 + 2 + 1] cycloaddition was initially established
by preparing alkynyl allene 1 according to the sequence
* To whom correspondence should be addressed: Tel: (304) 293-
3435 ext 4445. FAX: (304) 293-4904. e-mail: kbrummon@wvu.edu.
† Davis & Elkins College, Department of Chemistry, Elkins, WV
26241.
(1) Khand, I. U.; Knox, G. R.; Pauson, P. L.; Watts, W. E. J . Chem.
Soc., Chem. Commun. 1971, 36.
(2) Schore, N. E. In Comprehensive Organic Synthesis; Trost, B. M.,
Ed.; Pergamon: Oxford, 1991; Vol. 5, p 1037.
(3) Kent, J . L.; Wan, H.; Brummond, K. M. Tetrahedron Lett. 1995,
36, 2407. Brummond, K. M.; Wan, H. Tetrahedron Lett. 1998, 39, 931.
Since the initial report by ourselves other groups have reported [2 +
2 + 1] cycloadditions with alkynyl allenes. (a) Ahmar, M.; Antras, F.;
Cazes, B. Tetrahedron Lett. 1995, 36, 4417-4420. (b) Ahmar, M.;
Locatelli, C.; Colombier, D.; Cazes, B. Tetrahedron Lett. 1997, 38,
5281-5284. (c) Hicks, F. A.; Kablaoui, N. M.; Buchwald, S. L. J . Am.
Chem. Soc. 1996, 118, 9450-9451.
(5) Forman, B. M.; Tontonoz, P.; Chen, J .; Brun, R. P.; Spiegelman,
B. M.; Evans, R. M. Cell, 1995, 83, 803-812. Wahli, W.; Braissant,
O.; Desvergne, B. Chem. Biol. 1995, 2, 261. Turner, N. C. Drug
Discovery Today 1996, 1, 109.
(6) For the monosubstituted allenes complexation of the alkynes
with dicobalt octacarbonyl could be effected, but attempts to promote
cyclization resulted in decompostion or recovery of starting material.
(7) J eong, N.; Lee, S. J .; Lee, B. Y.; Chung, K. Y. Tetrahedron Lett.
1993, 34, 4027.
(4) McMorris, T. C.; Kelner, M. J .; Wang, W.; Estes, L. A.; Montoya,
M. A.; Taetle, R. J . Org. Chem. 1992, 57, 6876-6883.
S0022-3263(98)00548-9 CCC: $15.00 © 1998 American Chemical Society
Published on Web 09/01/1998

6536 J . Org. Chem., Vol. 63, No. 19, 1998
Brummond et al.
Sch em e 2
Ta ble 1. Mon osu bstitu ted Allen es
8 in 30% yield based upon recovered starting material.
The incorporation of a four-carbon tether in this P-K
cycloaddition gives very low yields and is thought to be
a result of the sensitivity of the cycloaddition to entropic
effects and competing polymerization of the allene moi-
ety. In all these examples using monosubstituted allenes,
cycloaddition occurred exclusively with the internal
π-bond of the allene (pathway A, Scheme 1).
1,3-Disu bstitu ted Allen es. Next, substitution pat-
terns on the allenes were varied in order to examine its
effect on the regiochemical outcome of the cycloaddition.
There are numerous natural products possessing substi-
tution at the terminus of the exocyclic olefin moiety of
the R-methylene cyclopentenone, and the allenic [2 + 2
+ 1] cycloaddition provides a direct route to this struc-
ture. Initially, the cyclizations of 1,3-disubstituted al-
lenes possessing a seven-carbon chain appended to the
terminus of the allene were examined. The long alkyl
chain was selected so that volatility of the starting
materials and the products would not affect the observed
yields. When 1,3-disubstituted alkynyl allene 9 was
treated with molybdenum hexacarbonyl/DMSO, cycload-
dition occurred exclusively via pathway A to give the
bicyclo[3.3.0]octane ring system 10 as a mixture of E:Z
isomers (2:1 ratio) in a 75% yield (entry 1, Table 2).8 To
determine if the E/Z ratio was an artifact of the cycliza-
tion conditions, an isomerization study was done by
submitting both pure 10-E and pure 10-Z to the molyb-
denum cyclization conditions. The isomers 10-E and
10-Z were separated using column chromatography (3%
ether/hexanes). When 10-E was submitted to the reac-
tion conditions, no isomerization was observed after 3
days, but small amounts of an isomeric dienone began
forming after 24 h. Alternatively, 10-Z showed some
isomerization to 10-E after 24 h with concomitant forma-
tion of the same dienone isomer seen in the E system.
However, we feel that isomerization of the product was
not a significant factor in the E:Z ratio since the duration
of the original cycloaddition (9 f 10) was only 10 h.
homogeneous. At this point no product is observed by
GC-MS. Soon afterward the solution turns to a greenish-
gray, and GC-MS shows that product formation is occur-
ring. Eventually a blue precipitate is formed on the walls
of the flask, and the starting material is no longer being
consumed. It is assumed that these color changes are
associated with the varying degrees of complexation of
the molybdenum, with the final blue precipitate being a
molybdenum carbonyl species that is no longer useful in
the reaction sequence.
Other monosubstituted allenes were also submitted to
the cyclization conditions and are depicted in Table 1.
Alkynyl allenes 3 and 5 were prepared possessing sub-
stituents on C-4 and C-5 of the tether. When R ) H
(compound 3, Table 1), the cyclization occurred in 47%
yield to give R-methylene cyclopentenone 4 as a 3:1
mixture of diastereomers. These diastereomers were
separated by flash column chromatography and it was
determined that the major isomer possesses an anti
relationship between the proton at the ring fusion and
the proton geminal to the hydroxyl moiety. This conclu-
sion is based upon the observed coupling constant for
these vicinal protons (10.1 Hz) which is in agreement
with the calculated coupling constant from the geometry
minimized structure using Macromodel (10.2 Hz). The
minor isomer possessing the syn relationship between
these protons shows no coupling which is in close agree-
ment with the calculated coupling (3.2 Hz). Protection
of the hydroxyl moiety as the MOM ether (compound 5,
Table 1) did not produce significant changes in the yield
(54%) and gave compound 6 in a 1:1 diastereomeric ratio
of products. Lengthening the tether was examined next.
Alkynyl allene 7 cyclized to give the bicyclo[4.3.0]nonane
(8) Reaction conditions were systematically varied in the conversion
of alkynyl allene 9 to dienone 10 in an effort to increase the overall
efficiency of this cycloaddition process. The efficiency of these reactions
were estimated by injecting aliquots of reaction mixtures on the GC-
MS and by using tridecane as an internal standard. Initially the
amount of dimethyl sulfoxide (DMSO) was varied from 5 to 10 to 15
equiv, and the amount of molybdenum hexacarbonyl (1.2 equiv) and
the temperature of the reaction (100 °C) were held constant. It was
found that the best product/internal standard ratios were obtained
when 10 equiv of DMSO were used. Next the optimal amount of
molybdenum hexacarbonyl was checked while holding the amount of
DMSO (10 equiv) and reaction temperature (100 °C) constant. The
amount of molybdenum hexacarbonyl was varied by 0.1 equiv from
1.2 to 1.8 equiv, and it was found that 1.5 equiv gave the best product/
internal standard ratios. Finally reaction temperatures were varied
by 10° increments from 90 to 130°, while keeping the amount of
molybdenum hexacarbonyl (1.5 equiv) and DMSO (10 equiv) constant.
Increasing the reaction temperature shortened the reaction time and
gave better product/internal standard ratios, but as the temperature
was raised higher than 110 °C the product/internal standard ratio
dropped. Thus the optimal reaction conditions as evidenced by this
study are Mo(CO)6 (1.5 equiv) and DMSO (10 equiv) in toluene at 110
°C.

An Intramolecular Allenic [2 + 2 + 1] Cycloaddition
J . Org. Chem., Vol. 63, No. 19, 1998 6537
Ta ble 2. 1,3-Disu bstitu ted Allen es
F igu r e 1.
Sch em e 3
rapidly when trimethylamine N-oxide was used as a
promoter10 instead of DMSO; however, the observed facial
selectivity was lower (compare entries 3 and 4, Table 2).
The separation of compounds 14,15-E and 15-Z was
effected by HPLC (silica column) eluting with 0.75%
EtOAc/hexanes, and the assignment of the cycloadduct
structures was based upon the 1H NMR spectra and NOE
studies (Figure 1). In particular, the most diagnostic
resonances appear as triplets at δ 5.86, 6.40, and 5.97
corresponding to the olefin protons He of 15-Z and 15-E
and Ha of the bicyclo[4.3.0]nonane ring system 14,
respectively. In the 15-Z isomer, an NOE (3.2%) was
observed between the olefin proton resonance and the
allylic methine proton resonance (He and Ha). There was
no observable NOE for these same proton resonances in
the 15-E isomer. This assignment is also in agreement
with the chemical shifts observed for the vinyl protons
where He of 15-E is shifted 0.51 ppm further downfield
than the same proton of 15-Z. Decoupling and correla-
tion experiments helped to characterize the bicyclo[4.3.0]-
nonane structure 14. In particular, irradiation of the
allylic protons (Hb) resulted in a singlet for vinylic proton
Ha showing them to be vicinal. Additionally, irradiation
of Hc simplifies Hb to a doublet and Hd to a singlet.
Finally, when the cyclization was effected in the
presence of Cp2Zr(n-Bu)2,11 the bicyclo[3.3.0]octane 15-E
was isolated as the major product in good yields (entry
6, Table 2). We have subsequently determined that this
notable facial selectivity is an artifact of the workup
conditions which involve the addition of 3 M HCl to the
reaction media. Treatment of the bicyclo[3.3.0]octane
15-Z (independently synthesized) to these workup condi-
tions resulted in the complete isomerization of the 15-Z
to 15-E in less than 15 min. In an effort to determine
the true stereochemical outcome of the zirconium-medi-
ated cyclization, we hydrolyzed zirconacycle intermediate
Phenyl-substituted allene 11 cyclized with slightly higher
stereoselectivity (5:1, E:Z) to form cyclopentanone 12.
This modest increase in stereoselectivity may be at-
tributed to a stereoelectronic effect caused by hindered
rotation around the allene phenyl bond.
Since we are interested in using this [2 + 2 + 1]
cycloaddition to prepare chiral R-methylene cyclopenten-
ones this apparent lack of facial selectivity resulting in
E and Z isomers concerned us. The Z-isomer results from
the addition of the metal-alkyne complex from the same
face of the allene as the R group and the E-isomer results
from the addition of the alkyne-metal complex form the
opposite face of the R group (Scheme 3). Thus, in an
effort to increase the facial selectivity, we turned to
dicobalt octacarbonyl [Co2(CO)8] as a metal promoter,
since dicobalt octacarbonyl has been used successfully in
the selective formation of diastereomers.9 Complexation
of the alkynyl allene 9 with Co2(CO)8 under standard
conditions affords metal complex 13. Subjection of 13
to a variety of cycloaddition conditions indeed resulted
in reactions that proceeded with much higher facial
selectivity; however, π-bond selectivity eroded resulting
in nearly 1:1 mixtures of bicyclo[4.3.0]nonane 14 and the
bicyclo[3.3.0]octane ring systems 15 (entries 3-5, Table
2). In the cobalt-mediated cyclizations, the highest yields
were obtained when the alkynes were precomplexed with
the cobalt and purified before being subjected to cycliza-
tion conditions. The reaction proceeded much more
(10) Shambayati, S.; Crowe, W. E.; Schreiber, S. L. Tetrahedron Lett.
1990, 31, 5289.
(9) Magnus, P.; Principe, L. M.; Slater, M. J . J . Org. Chem. 1987,
52, 1483-1486.
(11) Negishi, E. I.; Holmes, S. J .; Tour, J . M.; Miller, J . A. J . Am.
Chem. Soc. 1985, 107, 2568.

6538 J . Org. Chem., Vol. 63, No. 19, 1998
Brummond et al.
Ta ble 3. 3,3-Disu bstitu ted Allen es
Sch em e 4
17 affording dienes 18 and 19 in a 10:1 ratio (eq 1). This
selectivity remains synthetically appealing and can be
rationalized on the basis of the steric bulk of the
cyclopentadienyl ligands as shown in the two extreme
precyclization conformers A and B (Scheme 4). Con-
former B is predicted to be disfavored due to a severe
steric interaction between the alkyl group on the termi-
nus of the allene and the cyclopentadienyl rings. The
observed π-bond selectivity can be rationalized as follows.
The internal π-bond orbitals of conformer C are projected
toward the reactive zirconium-carbon bond. Whereas
the external π-bond orbitals are perpendicular to the
zirconium-carbon bond. Thus, we have shown that the
allenic [2 + 2 + 1] cycloaddition of 1,3-disubstituted
allenes could be directed to react with the internal π-bond
of the allene to afford R-methylene cyclopentenones
stereoselectively by simply changing the metal catalyst.
3,3-Disu bstitu ted Allen es. Next the cyclizations of
3,3-disubstituted allenes were investigated. The inef-
ficient processing of 2,2-disubstituted olefins appears to
be a weakness in many Pauson-Khand (P-K) systems,12
and the analogous 3,3-disubstituted allenes were pre-
dicted to be affected similarly. However, unlike the
olefinic P-K reaction, in the allenic variant cycloaddition
can occur with an alternate π-bond. The alkynyl allenes
utilized in this study were prepared via the addition of
the requisite alkynylmagnesium bromide to the ap-
propriate propargylic mesylate in the presence CuBr‚
LiBr.13 Treatment of 3-n-butyl-1,2-octadien-7-yne (20) to
molybdenum conditions resulted in the formation of the
bicyclo[4.3.0]nonane ring system 21 as the only product
in a 60% yield (entry 1, Table 3). This product arises
from cyclization with the external π-bond of the allene
(pathway B, Scheme 1). This result demonstrates a
dependence of the π-bond selectivity of the allenic [2 + 2
+ 1] reaction upon the substrate structure. Mono- and
1,3-disubstituted allenes undergo cyclization with the
internal π-bond whereas 3,3-disubstituted allenes utilize
the external π-bond. To date, there are only a few
examples of this type of substrate dependence in the [2
+ 2 + 1] reaction.14 Attempts to effect the cyclization of
an analogue of 20 (possessing a TMS moiety on the
terminus of the alkyne) using dicobalt octacarbonyl
resulted in the immediate decomposition of the starting
material. Likewise the zirconium-promoted cyclization
(13) Westmijze, H.; Vermeer, P. Synthesis 1979, 390.
(14) Borodkin, V. S.; Shapiro, N. A.; Azov, V. A.; Kochetkov, N. K.
Tetrahedron Lett. 1996, 37, 1489-1492; Ahmar, M.; Locatelli, C.;
Colombier, D.; Cazes, B. Tetrahedron Lett. 1997, 38, 5281.
(12) Knudson, M. J .; Schore, N. E. J . Org. Chem. 1984, 49, 5025.

An Intramolecular Allenic [2 + 2 + 1] Cycloaddition
J . Org. Chem., Vol. 63, No. 19, 1998 6539
Ta ble 4. Tr isu bstitu ted Allen es
Sch em e 5
gave very low conversions (0-16%) to the cycloadduct.
In an attempt to sterically direct the cyclization reac-
tion toward the internal double bond of the allene, a
silicon moiety was placed at the terminus of the allene
to give 22. Treatment of trisubstituted alkynyl allene
22 to molybdenum conditions gave the desilylated bicyclo-
[4.3.0]nonane ring system 21 in 59% yield (entry 2, Table
3). On the basis of GC-MS data, the desilylation occurred
prior to cyclization. Attempts to prepare the less labile
TBS-substituted allene in a manner similar to that used
for the preparation of 22 (n-BuLi, TBSCl or TBSOTf)
resulted in recovery of starting material. Cyclization of
a more functionalized precursor 23 occurred to give the
[5.6.5] ring system 24 in 42% yield (entry 3, Table 3).
The [2 + 2 + 1] cycloaddition of 3,3-disubstituted
allenes has also been used to prepare some interesting
carbocyclic skeletons possessing functionality that can
easily be manipulated to other substrates. Alkynyl
allenes 25, 28, and 31 were prepared using a method
developed in our laboratories for the direct conversion of
ketones to allenes.15 The conjugate addition of organo-
magnesium reagent 36 to 1-acetyl-1-cyclopentene16 and
1-acetyl-1-cyclohexene was effected using catalytic man-
ganese(II) chloride (30%) and copper(I) chloride (3%)17
followed by an in situ trap of the enolate with diethyl
chlorophosphate to afford the desired enol phosphates
(Scheme 5). Elimination of the phosphate to give the
allene is then carried out by the addition of LDA at low
temperature. The trimethylsilyl moiety can be removed
from the alkyne terminus with tetra-n-butylammonium
fluoride. Exposure of the alkynyl allenes to molybdenum
hexacarbonyl/DMSO affords the cycloadducts 26, 29, and
32 (entries 4-6, Table 3). The subjection of the alkynyl
allene 34 to molybdenum [2 + 2 + 1] cycloaddition
conditions gave only the linear [5.5.5] ring system 35 in
a 66% yield with no evidence of the angular [5.4.5] ring
system. The rapid assembly of these ring systems
demonstrates the applicability of these two methods and
provides skeletons visible in naturally occurring com-
pounds.18
allenic [2 + 2 + 1] reaction. Cycloaddition of 1,3-
disubstituted allenes afford mixtures of several possible
cycloadducts. However, we have shown that good control
over the product ratio can be obtained by altering the
cycloaddition conditions and that the regiochemistry can
be directed to the internal π-bond depending upon the
metal used. 3,3-Disubstituted and trisubstituted allenes
undergo cycloaddition with the least substituted π-bond
of the allene. This affords the bicyclo[4.3.0]nonane ring
system selectively. We are continuing to explore the
scope and limitations of the allenic variant of the [2 + 2
+ 1] cycloaddition and its application to synthesis.
Exp er im en ta l Section
Gen er a l Meth od s. Unless otherwise noted, all reactions
were carried out under Ar in flame-dried glassware using
standard syringe, cannula, and septa techniques. Tetrahy-
drofuran and diethyl ether were freshly distilled from sodium
benzophenone ketyl. Dimethyl sulfoxide and toluene were
distilled from calcium hydride and stored over molecular sieves
4 Å. Dichloromethane and benzene were freshly distilled from
calcium hydride. Thin-layer chromatography was performed
using precoated Kieselgel 60 F-254 plates. Flash chromatog-
raphy was performed using Baker flash silica gel 60 (40 µm).
Molybdenum hexacarbonyl, dicobalt octacarbonyl, and biscy-
clopentadienyl zirconium dichloride were all purchased from
Strem chemicals, used as purchased and stored under Ar.
5-(Trimethylsilyl)-1-chloro-4-pentyne was purchased from Farch-
an. NMR spectra were obtained on a 270 MHz NMR. 1H
NMR shifts were obtained in CDCl3 and reported in ppm
relative to the solvent shift of residual chloroform of δ 7.26.
13C NMR shifts were obtained in CDCl3 and reported in ppm
relative to CDCl3 77.0. GC mass spectra were obtained at an
ionization potential of 70 eV on a GC/MSD. IR spectra were
obtained on a 1600 FT-IR spectrometer. High-resolution MS
were obtained from the Department of Chemistry, University
of California at Riverside.
1-(Tr im eth ysilyl)-6,7-octa d ien -1-yn e (1). 1-(Trimethyl-
silyl)-5-bromo-1-pentyne was prepared according to the pro-
cedure described by Bailey and Aspris.19 A solution of
1-(trimethylsilyl)-5-bromo-1-pentyne (3.14 g, 14.3 mmol) in
Et2O (65 mL) was added dropwise to a suspension of magne-
sium turnings (0.696 g, 28.6 mmol) in Et2O. The reaction was
initiated with slight heating and then allowed to stir at room
temperature for 2 h. The Grignard reagent was added to a
cooled (-5 °C) mixture of CuBr (20.5 mg, 0.143 mmol) and
methyl propargyl ether (1.51 g, 21.5 mmol) in Et2O (50 mL).
The reaction was stirred at -5 °C for 2 h and then diluted
with Et2O (50 mL) and poured into an ice-cold 1:1 mixture of
1 N HCl:saturated NH4Cl (100 mL). The aqueous layer was
separated and washed with Et2O (20 mL). The combined
Finally, we have shown that trisubstituted allenes
undergo cyclization exclusively with the less substituted
π-bond of the allene as evidenced by entries 1 and 2 in
Table 4. Treatment of alkynyl allene 37 and 39 to the
standard molybdenum cyclization conditions afforded
dienones 38 and 40.
These preliminary studies have demonstrated a sub-
strate structure dependence upon the course of the allenic
[2 + 2 + 1] reaction. Monosubstituted allenes afford
R-methylene cyclopentenones as the only cycloadduct.
Disubstitution on the allene alters the course of the
(15) Brummond, K. M.; Dingess, E. A.; Kent, J . L. J . Org. Chem.
1996, 61, 6096.
(16) House, H. O.; Phillips, W. V.; Sayer, T. S. B.; Yau, C. C.; J .
Org. Chem. 1978, 43, 700.
(17) Alami, M.; Marquais, S.; Cahiez, G. Org. Synth. 1995, 72, 135.
(18) Mehta, G.; Srikrishna, A. Chem. Rev. 1997, 97, 671.
(19) Bailey, W. F.; Aspris, P. H. J . Org. Chem. 1995, 60, 754.

6540 J . Org. Chem., Vol. 63, No. 19, 1998
Brummond et al.
organic extracts were dried over MgSO4 and concentrated in
vacuo. Chromatography (1% Et2O/pentane) afforded 1.54 g
(61%) of the alkynyl allene 1 as a colorless oil. 1H NMR (270
MHz, CDCl3) δ 5.08 (dt, J ) 13.3, 6.7 Hz, 1H), 4.66 (dt, J )
6.7, 3.2 Hz, 2H), 2.25 (t, J ) 7.2 Hz, 2H), 2.08 (m, 2H), 1.62
(quin, J ) 7.2 Hz, 2H), 0.12 (s, 9H); 13C NMR (67.9 MHz,
CDCl3) δ 208.7, 107.1, 89.2, 84.8, 75.1, 28.0, 27.3, 19.3, 0.2; IR
(neat) 2175, 1957, 1249, 842 cm-1; MS (GC/MS) m/z 163 (M+
- 15), 147, 135, 118, 109.
4,4-Dim eth yl-5-h ydr oxy-1-(tr im eth ylsilyl)-6,7-octadien -
1-yn e (3). To a solution of 4,4-dimethyl-5-hydroxy-1-(trim-
ethylsilyl)octa-1,6-diyne (66.5 mg, 0.32 mmol) in dioxane (3
mL) were added copper(I) iodide (23.0 mg, 0.16 mmol),
paraformaldehyde (24.0 mg, 0.80 mmol), and diisopropylamine
(90 µL, 0.64 mmol). The reaction mixture was refluxed for 3
h and cooled to room temperature, dioxane was evaporated in
vacuo, and the residue was dissolved in CH2Cl2 (10 mL) and
washed with 10% ammonia in brine (2 × 5 mL), HCl solution
(pH ) 2, 2 × 5 mL), and water (5 mL). The organic layer was
dried over MgSO4, removal of the solvent in vacuo and
purification by flash chromatography on silica gel (eluting with
5% EtOAc/hexane) furnished the title compound (23 mg, 32%).
1H NMR (270 MHz, CDCl3) δ 5.28 (q, J ) 6.6 Hz, 1H), 4.87
(dd, J ) 2.4, 6.7 Hz, 2H), 4.07-4.00 (m, 1H), 2.30 (d, J ) 16.8
Hz, 1H), 2.18 (d, J ) 16.8 Hz, 1H), 1.94 (d, J ) 5.3 Hz, 1H),
0.99 (s, 3H), 0.98 (s, 3H), 0.15 (s, 9H); 13C NMR (67.9 MHz,
CDCl3) δ 207.5, 105.1, 91.4, 87.0, 77.5, 75.6, 38.6, 29.9, 23.1,
22.2, 0.1; IR (neat) 3449, 2174, 1956, 1037, 842 cm-1; MS (GC/
MS) m/z 207, 191, 167, 154, 139, 110; HRMS m/z (M+) calcd
222.1440, obsd 222.1441.
4,4-Dim eth yl-5-[(m eth oxym eth yl)oxy]-1-(tr im eth ylsi-
lyl)-6,7-octa d ien -1-yn e (5). To a solution of 4,4-dimethyl-
5-hydroxy-1-(trimethylsilyl)-6,7-octadien-1-yne (46 mg, 0.21
mmol) and N,N-diisopropylethylamine (162 µL, 0.93 mmol) in
CH2Cl2 (2 mL) at 0 °C was added chloromethyl methyl ether
(47 µL, 0.62 mmol) dropwise. The cooling bath was removed,
and the reaction was stirred at room temperature for 24 h.
The reaction was diluted with CH2Cl2 (5 mL), washed with
NaHCO3, (2 × 5 mL) brine (5 mL), and dried over Na2SO4.
Removal of the solvent in vacuo and purification by flash
chromatography on silica gel (eluting with 3% EtOAc/hexane)
afforded 4,4-dimethyl-5-[(methoxymethyl)oxy]-1-(trimethylsi-
lyl)-6,7-octadien-1-yne (43.9 mg, 80%). 1H NMR (270 MHz,
CDCl3) δ 4.98 (dt, J ) 6.6, 8.8 Hz, 1H), 4.79 (d, J ) 6.6 Hz,
1H), 4.77-4.74 (m, 2H), 4.52 (d, J ) 6.6 Hz, 1H), 3.96 (d, J )
8.8 Hz, 1H), 3.38 (s, 3H), 2.32 (d, J ) 16.8 Hz, 1H), 2.21 (d, J
) 16.8 Hz, 1H), 1.00 (s, 3H), 0.98 (s, 3H), 0.14 (s, 9H); 13C NMR
(67.9 MHz, CDCl3) δ 209.8, 105.2, 94.0, 87.6, 86.6, 80.1, 75.1,
55.9, 38.3, 30.1, 23.2, 22.2, 0.11; IR (neat) 2174, 1955, 1151,
1039, 844 cm-1; MS (GC/MS) m/z 251, 221, 191, 189, 147, 113.
1-(Tr im eth ylsilyl)-1,2-n on a d ien -8-yn e (7). 6-Bromo-1-
(trimethylsilyl)-1-hexyne was prepared according to a proce-
dure described by Bailey and Aspris.19 A solution of 6-bromo-
1-(trimethylsilyl)-1-hexyne (1.05 g, 4.52 mmol) in Et2O (20 mL)
was added dropwise to a suspension of magnesium turnings
(220 mg, 9.04 mmol) in Et2O (20 mL). The reaction was
initiated with slight heating and then allowed to stir with
frequent warming for 1 h. The Grignard reagent was added
to a cooled (-5 °C) mixture of CuBr (7.0 mg, 0.05 mmol) and
methyl propargyl ether (475 mg, 678 mmol) in Et2O (15 mL).
The reaction was stirred at -5 °C for 2 h and then diluted
with Et2O (15 mL) and poured into an ice-cold 1:1 mixture of
1 N HCl:saturated NH4Cl (30 mL). The aqueous layer was
separated and washed with Et2O (10 mL). The combined
organic extracts were dried over MgSO4 and concentrated in
vacuo. Chromatography (hexanes) afforded 264 mg (30%) of
alkynyl allene 7 as a colorless oil.1H NMR (270 MHz, CDCl3)
δ 5.08 (quin, J ) 6.7 Hz, 1H), 4.65 (dt, J ) 6.7, 3.2 Hz, 2H),
2.21 (t, J ) 6.7 Hz, 2H), 2.00 (m, 2H), 1.61-1.44 (m, 4H), 0.13
(s, 9H); 13C NMR (67.9 MHz, CDCl3) δ 208.6, 107.5, 89.8, 84.5,
74.8, 28.2, 28.1, 27.7, 19.7, 0.21; IR (neat) 2175, 1957, 1249,
841 cm-1; MS (GC/MS) m/z 177.1 (M+ - 15), 149, 135, 117,
109.
nesium chloride (1.60 g, 16.8 mmol), THF (25 mL), and
potassium (1.25 g, 32.0 mmol). The mixture was heated to
reflux for 3 h and cooled to room temperature. 1-Chloro-5-
(trimethylsilyl)-4-pentyne (2.20 g, 12.6 mmol) in THF (10 mL)
was added slowly to the mixture, and the reaction was stirred
at room temperature for another 30 min. Into a 100 mL flask
were added copper(I)bromide (1.15 g, 8.0 mmol) and lithium
bromide (0.70 g, 8.1 mmol). The combined solids were dried
at 150-160 °C/10-20 mmHg for 45 min or 120 °C/0.06 mmHg
for 5 h and then cooled to room temperature under argon. THF
(8 mL) was then added. The resulting solution was cooled to
-50 °C, and the Grignard reagent prepared above was
cannulated into this flask slowly. The mixture was stirred at
-50 °C for another 30 min, and a solution of 3-(methylsulfo-
nyloxy)-1-decyne (1.86 g, 8.0 mmol) in THF (10 mL) was added
dropwise. After stirring for an additional 30 min at -50 °C,
the cooling bath was removed, and the reaction mixture was
stirred for 3 h at room temperature and then poured into a
solution of sodium cyanide (2 g) in a solution of saturated NH4-
Cl (50 mL). After vigorous shaking, the product was extracted
with pentane (3 × 50 mL), and the combined organic layers
were washed with water (50 mL) and dried over MgSO4. The
solvent was removed in vacuo, and purification of the residue
by flash chromatography on silica gel (eluting with pentane)
provided 1-(trimethylsilyl)-6,7-pentadecadien-1-yne (16) (2.1
g, 96%) as a colorless oil. 1H NMR (270 MHz, CDCl3) δ 5.13-
4.99 (m, 2H), 2.25 (t, J ) 7.2 Hz, 2H), 2.10-1.91 (m, 4H), 1.61
(quin, J ) 7.3 Hz, 2H), 1.40-1.25 (m, 10H), 0.87 (t, J ) 6.6
Hz, 3H), 0.13 (s, 9H); 13C NMR (67.9 MHz, CDCl3) δ 204.0,
107.2, 91.3, 89.9, 84.5, 31.9, 29.2, 29.2, 29.1, 28.9, 28.1, 28.0,
22.7, 19.2, 14.1, 0.14; IR (neat) 2176, 1962, 1458, 1249, 840
cm-1; MS (GC/MS) m/z 276 (M+), 261, 233, 219, 203, 159, 145,
131; HRMS m/z (M+ + 1) calcd 277.2352, obsd 277.2356.
(B) Rep r esen ta tive P r oced u r e for Desilyla tion of
Alk yn yl Allen es 6,7-P en ta d eca d ien -1-yn e (9). To a solu-
tion of 1-(trimethylsilyl)-6,7-pentadecadien-1-yne (98 mg, 0.36
mmol) in THF (4 mL) at 0 °C was added dropwise a solution
of 1.0 M tetra-n-butylammonium fluoride (TBAF) in THF (0.43
mL, 0.43 mmol). The resulting solution was stirred at room
temperature for 2 h, then water (30 mL) was added. The
mixture was extracted with pentane (3 × 30 mL), and the
combined extracts were washed with water (30 mL) and dried
over MgSO4. Removal of the solvent in vacuo and purification
of the residue by flash chromatography on silica gel (eluting
with pentane) afforded 6,7-pentadecadien-1-yne (9) (66 mg,
90%) as a colorless oil. 1H NMR (270 MHz, CDCl3) δ 5.13-
5.01 (m, 2H), 2.23 (dt, J ) 2.6, 7.1 Hz, 2H), 2.13-2.04 (m, 2H),
1.99-1.93 (m, 3H), 1.64 (quin, J ) 7.1 Hz, 2H), 1.40-1.27 (m,
10H), 0.88 (t, J ) 6.5 Hz, 3H); 13C NMR (67.9 MHz, CDCl3) δ
204.0, 91.4, 89.8, 84.3, 68.3, 31.9, 29.2, 29.1, 29.0, 28.9, 27.9,
22.7, 17.8, 14.1; IR (neat) 2120, 1962, 1457, 1252, 1070, 874
cm-1; MS (GC/MS) m/z 189 (M-15), 175, 147, 133, 119, 105;
HRMS m/z (M+) calcd 204.1878, obsd 204.1884.
8-P h en yl-6,7-octa d ien -1-yn e (11). Using the standard
procedure for the preparation of alkynyl allenes, method A, a
flask was charged with anhydrous magnesium chloride (1.4
g, 14.7 mmol), THF (25 mL), and potassium (1.1 g, 28 mmol).
The mixture was heated to reflux for 3 h, cooled to room
temperature, and 1-chloro-5-(trimethylsilyl)-4-pentyne (1.83 g,
10.5 mmol) in THF (10 mL) was added slowly. The mixture
was stirred at room temperature for another 30 min.
Into a 100 mL flask were added copper(I) bromide (1.0 g,
7.0 mmol) and lithium bromide (0.61 g, 7.0 mmol). The
combined solids were dried at 150-160 °C/10-20 mmHg for
45 min or 120 °C/0.06 mmHg for 5 h and then cooled to room
temperature under argon. (1-Phenyl-1-(methylsulfonyloxy)-
2-propyne can be prepared while drying the solids, vide infra.)
THF (15 mL) was then added, and the resulting solution was
cooled to -50 °C. The Grignard reagent prepared above was
cannulated into this flask over 20 min, and the mixture was
stirred at -50 °C for 30 min.
To a solution of 1-phenyl-2-propyn-1-ol (0.85 mL, 7.0 mmol)
and lithium bromide (0.61 g, 7.0 mmol) in THF (10 mL) was
added n-butyllithium (4.4 mL of a 1.6 M solution in hexane,
7.0 mmol) at -50 °C. After stirring for 30 min, the alkoxide
(A) Rep r esen ta tive P r oced u r e for th e P r ep a r a tion of
th e Alk yn yl Allen es. 1-(Tr im eth ylsilyl)-6,7-p en ta d eca -
d ien -1-yn e (16). A flask was charged with anhydrous mag-

An Intramolecular Allenic [2 + 2 + 1] Cycloaddition
J . Org. Chem., Vol. 63, No. 19, 1998 6541
solution was cannulated into a solution of methanesulfonyl
chloride (0.54 mL, 7.0 mmol) in THF (10 mL) at -50 °C over
10 min. The resulting solution was stirred for 1 h, and then
the organocopper reagent prepared above was cannulated into
this flask over 25 min. The reaction mixture was stirred for
an additional 30 min at -50 °C, the cooling bath was removed,
and the reaction was stirred for 3 h. The reaction mixture
was poured into a solution of sodium cyanide (2 g) and
saturated NH4Cl (50 mL). After vigorous shaking, the product
was extracted with pentane (3 × 50 mL), and the combined
organic layers were washed with water (50 mL) and dried over
MgSO4. The solvent was removed in vacuo, and purification
by flash chromatography on silica gel (eluting with pentane)
provided 8-ph en yl-1-(tr im eth ylsilyl)-6,7-octadien -1-yn e (1.48
g, 83%). 1H NMR (270 MHz, CDCl3) δ 7.37-7.20 (m, 5H), 6.20
(dt, J ) 3.1, 6.3 Hz, 1H), 5.62 (q, J ) 6.5 Hz, 1H), 2.36 (t, J )
7.0 Hz, 2H), 2.28 (dt, J ) 2.8, 7.1 Hz, 2H), 1.76 (quin, J ) 7.1
Hz, 2H), 0.21 (s, 9H); 13C NMR (67.9 MHz, CDCl3) δ 205.2,
134.8, 128.5, 126.7, 126.5, 106.8, 94.9, 94.1, 84.8, 27.8, 27.7,
19.3, 0.1; IR (neat) 2173, 1948, 1706, 1598, 1249, 1027; MS
(GC/MS) m/z 239, 223, 195, 180, 141, 129, 115, 73.
Following the representative procedure for desilylation of
alkynyl allenes, method B, 8-p h en yl-1-(tr im eth ylsilyl)-6,7-
octa d ien -1-yn e (329 mg, 1.30 mmol) was treated with TBAF
(1.55 mL, 1.55 mmol) to afford 8-p h en yl-6,7-octa d ien -1-yn e
(11) (170 mg, 72%) as an oil. 1H NMR (270 MHz, CDCl3) δ
7.36-7.18 (m, 5H), 6.18 (dt, J ) 3.2, 6.3 Hz, 1H), 5.60 (q, J )
6.5 Hz, 1H), 2.33-2.23 (m, 4H), 1.99 (t, J ) 2.6 Hz, 1H), 1.81
(m, 2H); 13C NMR (67.9 MHz, CDCl3) δ 205.2, 134.8, 128.5,
126.7, 126.6, 95.0, 94.0, 84.0, 68.6, 27.7, 27.6, 17.9; IR (neat)
2116, 1948, 1597, 1495, 1458, 879; MS (GC/MS) m/z 181, 167,
154, 128, 115, 102.
reaction was cooled to -78 °C, and TMSCl (45 µL, 0.35 mmol)
was added. The reaction solution was allowed to warm to room
temperature over 2 h and saturated NH4Cl was added. The
aqueous layer was extracted with pentane (3 × 10 mL), and
the combined extracts were washed with water (10 mL) and
then dried over MgSO4. After removal of the solvent in vacuo,
the residue was dissolved in CH3OH/THF (4:1, 2.5 mL), and
K2CO3 (72 mg, 0.52 mmol) was added. The reaction mixture
was stirred for 12 h and then diluted with water, and the
mixture was extracted with pentane (3 × 10 mL). The
combined extracts were washed with water (10 mL) and then
dried over MgSO4. Removal of the solvent in vacuo and
purification by flash chromatography (eluting with pentane)
furnished 3-n-butyl-1-(trimethylsilyl)-1,2-octadien-7-yne (22)
(44 mg, 67%) as a colorless oil. 1H NMR (270 MHz, C6D6) δ
5.03 (quin, J ) 3.8 Hz, 1H), 2.05 (dt, J ) 2.6, 7.1 Hz, 2H),
1.99-1.90 (m, 2H), 1.88-1.81 (m, 2H), 1.77 (t, J ) 2.7 Hz, 1H),
1.61 (quin, J ) 7.1 Hz, 2H), 1.45-1.22 (m, 4H), 0.88 (t, J )
7.1 Hz, 3H), 0.12 (s, 9H); 13C NMR (67.9 MHz, CDCl3) δ 208.1,
95.9, 84.5, 84.0, 68.3, 31.5, 30.7, 30.0, 26.7, 22.5, 18.2, 14.0,
-0.7; IR (neat) 1939, 1248, 840 cm-1; MS (GC/MS) m/z 219
(M+ - 15), 192, 177, 161, 131, 117, 105.
[1R*,2R*,3R*]-1-(ter t-Bu tyld im eth ylsilyloxy)-2-(1-m e-
th ylallen yl)-3-(2-pr opyn yl)-5,5-dim eth ylcyclopen tan e (23).
This procedure was performed according to that reported by
Inanaga.20 To a solution of [1R*,2S*,3R*]-1-(tert-butyldim-
ethylsilyloxy)-2-(1-methyl-1-(benzoyloxy)-2-propyne)-3-(2-pro-
pynyl)-5,5-dimethylcyclopentane (42.5 mg, 0.097 mmol), tetrakis-
(triphenylphosphine)palladium (5.6 mg), and 2,4-dimethyl-3-
pentanol (15 µL, 0.11 mmol) in THF (2 mL) at 40 °C was added
a 0.1 M solution of SmI2 in THF (7.2 mL, 0.72 mmol). After
stirring at this temperature for 3 h, the reaction mixture was
poured into saturated NH4Cl (30 mL) and filtered through a
pad of Celite and Florisil. The filtrate was extracted with Et2O
(3 × 20 mL). The combined organic layers were washed with
brine (30 mL) and dried over MgSO4. Removal of the solvent
in vacuo and purification by flash chromatography on silica
gel (eluting with hexane) furnished the compound 23 (19 mg,
62%) as a colorless oil. 1H NMR (270 MHz, CDCl3) δ 4.60 (q,
J ) 3.0 Hz, 2H), 3.5 (d, J ) 8.1 Hz, 1H), 2.35-2.27 (m, 1H),
2.14-2.03 (m, 2H), 1.93-1.80 (m, 2H), 1.73-1.63 (m, 4H), 1.45
(dd, J ) 9.2, 12.1 Hz, 1H), 0.96 (s, 3H), 0.91 (s, 3H), 0.87 (s,
9H), 0.14 (s, 3H), 0.00 (s, 3H); 13C NMR (67.9 MHz, CDCl3) δ
207.2, 98.5, 84.4, 83.2, 74.3, 68.9, 55.9, 43.7, 40.2, 37.2, 28.9,
26.0, 24.9, 23.1, 18.2, 17.3, -4.1, -4.4; IR (neat) 2107, 1956,
1-(Tr im eth ylsilyl)-6,7-p en ta d eca d ien -1-yn e-Hexa ca r -
bon yld icoba lt Com p lex (13). To a solution of 1-(trimeth-
ylsilyl)-6,7-pentadecadien-1-yne (16) (100 mg, 0.39 mmol) in
benzene (4 mL) was added dicobalt octacarbonyl (146 mg, 0.43
mmol) at room temperature. After stirring 2 h, the solvent
was removed in vacuo, and the residue was subjected to flash
chromatography using hexane as the eluent to give the title
complex 13 (137 mg, 75%). 1H NMR (270 MHz, CDCl3) δ 5.13
(quin, J ) 4.7 Hz, 2H), 3.14-2.86 (m, 2H), 2.18-2.08 (m, 2H),
2.01-1.92 (m, 2H), 1.74 (quin, J ) 7.6 Hz, 2H), 1.41-1.27 (m,
10 H), 0.88 (t, J ) 6.9 Hz, 3H), 0.30 (s, 9H); 13C NMR (67.9
MHz, CDCl3) δ 204.0, 200.5, 112.5, 91.9, 90.0, 78.9, 34.8, 31.9,
31.7, 29.1, 28.9, 28.6, 22.7, 14.1, 0.7; IR (neat) 2929, 2857, 2012,
1853, 1659, 1587, 1037 cm-1
.
1464, 1250, 1127, 875, 836 cm-1; MS (GC/MS) m/z 303 (M+
15), 261, 221, 187, 147, 129.
-
6-n -Bu t yl-1-(t r im et h ylsilyl)-6,7-oct a d ien -1-yn e. This
compound was prepared from 1-(methylsulfonyloxy)-2-heptyne
(1.5 g, 7.9 mmol) using representative procedure A to provide
6-n-butyl-1-(trimethylsilyl)-6,7-octadien-1-yne (1.84 g, 100%)
as a colorless oil: 1H NMR (270 MHz, CDCl3) δ 4.65 (quin, J
) 3.2 Hz, 2H), 2.23 (t, J ) 7.1 Hz), 2.05-1.96 (m, 2H), 1.95-
1.87 (m, 2H), 1.69-1.57 (m, 2H), 1.45-1.24 (m, 4H), 0.88 (t, J
) 6.8 Hz, 3H), 0.12 (s, 9H); 13C NMR (67.9 MHz, CDCl3) δ
205.6, 107.2, 102.3, 84.5, 75.6, 31.9, 30.9, 29.7, 26.5, 22.4, 19.4,
13.9, 0.13; IR (neat) 2957, 2860, 2175, 1957, 1456, 1249, 1035,
844 cm-1; MS (GC/MS) m/z 234, 219, 191, 163, 131, 109; HRMS
m/z (M+) calcd 234.1804, obsd 234.1805.
3-n -Bu tyl-1,2-octa d ien -7-yn e (20). Following the experi-
mental procedure for the desilylation of alkynyl allenes,
method B, 3-n-butyl-8-(trimethylsilyl)-1,2-octadien-7-yne (0.57
g, 2.4 mmol) afforded 3-n-butyl-1,2-octadien-7-yne 20 (0.32 g,
82%) as a colorless oil. 1H NMR (270 MHz, CDCl3) δ 4.65
(quin, J ) 3.2 Hz, 2H), 2.21 (dt, J ) 2.6, 7.1 Hz, 2H), 2.06-
1.99 (m, 2H), 1.94-1.90 (m, 3H), 1.71-1.60 (quin, J ) 7.3 Hz,
2H), 1.43-1.25 (m, 4H), 0.89 (t, J ) 6.9 Hz, 3H); 13C NMR
(67.9 MHz, CDCl3) δ 205.5, 102.4, 84.3, 75.5, 68.3, 31.9, 30.9,
29.6, 26.3, 22.4, 18.0, 13.9; IR (neat) 2119, 1957, 1456, 846
cm-1; MS (GC/MS) m/z 147 (M+ - 15), 133, 119, 117, 105;
HRMS m/z (M+) calcd 162.1409, obsd 162.1403.
Repr esen tative Exper im en tal P r ocedu r e for th e P r epa-
r a tion of Allen ylcycloa lk a n es 25, 28, a n d 31. A flask was
charged with anhydrous magnesium chloride (0.95 g, 10
mmol), THF (15 mL), and potassium (0.75 g, 19 mmol). The
mixture was heated to reflux for 3 h and cooled to room
temperature. 1-Bromo-4-(trimethylsilyl)-3-pentyne (1.64 g, 8.0
mmol) in THF (5 mL) was added over 15 min, and the resulting
mixture was stirred at room temperature for 30 min.
A 50 mL flask charged with MnCl2 (150 mg, 1.2 mmol) and
LiCl (102 mg, 2.4 mmol) was heated at 200 °C under vacuum
(0.1 mmHg) for 6 h and then cooled to room temperature under
argon. Copper(I) chloride (12 mg, 0.12 mmol), 1-acetyl-1-
cyclopentene (440 mg, 4.0 mmol), and THF (8 mL) were added.
The mixture was stirred at room temperature until dissolution
was complete and then cooled to 0 °C. The Grignard reagent
was cannulated to this solution over 25 min, and stirring was
continued for 1.5 h at 0 °C. Diethyl chlorophosphate (1.16 mL,
8.0 mmol) was added dropwise, and the resulting reaction
mixture was stirred at room temperature for 12 h. Saturated
NH4Cl was added, the mixture was extracted with Et2O (3 ×
50 mL), and the combined extracts were dried over MgSO4.
Removal of the solvent in vacuo and purification by flash
3-n -Bu tyl-1-(tr im eth ylsilyl)-1,2-octa d ien -7-yn e (22). To
a solution of 3-n-butyl-8-(trimethylsilyl)-1,2-octadien-7-yne (66
mg, 0.28 mmol) in THF (2 mL) at -30 °C was added
n-butyllithium (0.21 mL of a 1.6 M solution in hexane, 0.34
mmol) dropwise. After stirring at -30 °C for 30 min, the
(20) Mikami, K.; Yoshida, A.; Matsumoto, S.; Feng, F.; Matsumoto,
Y.; Sugino, A.; Hanamoto, T.; Inanaga, J . Tetrahedron Lett. 1995, 36,
907. Tabuchi, T.; Inanaga, J .; Yamaguchi, M. Tetrahedron Lett. 1986,
27, 5237.

6542 J . Org. Chem., Vol. 63, No. 19, 1998
Brummond et al.
chromatography on silica gel (eluting with 25% EtOAc/hexane)
afforded the enol phosphate (1.05 g, 70%) as a colorless oil.
To a solution of the enol phosphate (1.05 g, 2.82 mmol) in
THF (10 mL) at -78 °C was added freshly prepared LDA (9.0
mmol) in THF (15 mL) slowly. The resulting solution was
stirred at -78 °C for 3 h and then poured onto pentane (40
mL) and ice-water (20 mL). The aqueous layer was extracted
with pentane (3 × 20 mL), and the combined extracts were
washed successively with cold 1 M HCl, water, saturated
NaHCO3, water, and brine and then dried over MgSO4.
Removal of the solvent in vacuo and purification by flash
chromatography on silica gel (eluting with pentane) afforded
1-vinylidene-2-[4-(trimethylsilyl)-3-butynyl]-cyclopentane (28)
(0.39 g, 64%) as a colorless oil.
1-Vin ylid en e-2-[4-(tr im eth ylsilyl)-3-bu tyn yl]cyclop en -
ta n e (28). 1H NMR (270 MHz, CDCl3) δ 4.76-4.63 (m, 2H),
2.62-2.54 (m, 1H), 2.44-2.34 (m, 2H), 2.28 (t, J ) 7.5 Hz, 2H),
1.96-1.66 (m, 3H), 1.64-1.44 (m, 2H), 1.32-1.17 (m, 1H), 0.12
(s, 9H); 13C NMR (67.9 MHz, CDCl3) δ 202.2, 107.6, 106.7, 84.2,
76.7, 42.2, 34.4, 33.0, 30.8, 25.2, 18.5, 0.17; IR (neat) 2174,
1940, 1449, 1042, 842 cm-1; MS (GC/MS) m/z 218, 203, 175,
159, 144, 129.
8.1 mmol), 2-methyl-2-hydroxyl-1-butyne (0.78 mL, 8.0 mmol),
lithium bromide (0.7 g, 8.1 mmol), n-butyllithium (5.0 mL of
a 1.6 M solution in hexane, 8.0 mmol), and methanesulfonyl
chloride (0.62 mL, 8.0 mmol). Purification by flash chroma-
tography on silica gel (eluting with pentane) provided 8-meth-
yl-1-(trimethylsilyl)-6,7-nonadien-1-yne (1.44 g, 88%). 1H
NMR (270 MHz, CDCl3) δ 4.96-4.86 (m, 1H), 2.25 (t, J ) 7.2
Hz, 2H), 2.02 (dt, J ) 6.9, 7.1 Hz, 2H), 1.69-1.54 (m, 8H),
0.13 (s, 9H); 13C NMR (67.9 MHz, CDCl3) δ 201.9, 107.4, 95.1,
87.8, 84.4, 28.3, 28.0, 20.7, 19.1, 0.16; IR (neat) 2936, 2857,
2175, 1445, 1249, 1049, 841, 760 cm-1; MS (GC/MS) m/z 191,
173, 149, 132, 117, 109, 73, 67. Following the representative
procedure for desilylation of alkynyl allenes, method B,
8-methyl-1-(trimethylsilyl)-6,7-nonadien-1-yne (0.412 g, 2.0
mmol) was treated with TBAF to afford 8-methyl-6,7-nona-
1
dien-1-yne (0.18 g, 67%) as a colorless oil. 1H NMR H NMR
(270 MHz, CDCl3) δ 4.97-4.86 (m, 1H), 2.21 (dt, J ) 2.6, 7.2
Hz, 2H), 2.04 (dt, J ) 6.7, 7.1 Hz, 2H), 1.92 (t, J ) 2.7 Hz,
1H), 1.68-1.56 (m, 8H); 13C NMR (67.9 MHz, CDCl3) δ 201.9,
95.3, 87.7, 84.4, 68.2, 28.1, 27.9, 20.6, 17.7; IR (neat) 3303,
2118, 1967, 1362, 1233 cm-1; MS (GC/MS) m/z 133, 119, 105;
HRMS m/z (M+) calcd 134.1096 obsd 134.1087.
1-Vin ylid en e-2-(3-bu tyn yl)cyclop en ta n e (25). Follow-
ing the experimental procedure for desilylation of alkynyl
allenes, method B, 1-vinylidene-2-[4-(trimethylsilyl)-3-butynyl]-
cyclopentane (28) (0.39 g, 1.8 mmol) was treated with TBAF
to afford 1-vinylidene-2-(3-butynyl)cyclopentane (25) (0.14 g,
53%) as a colorless oil. 1H NMR (270 MHz, CDCl3) δ 4.77-
4.64 (m, 2H), 2.70-2.55 (m, 1H), 2.46-2.36 (m, 2H), 2.30-
2.22 (m, 2H), 1.98-1.68 (m, 4H), 1.65-1.46 (m, 2H), 1.32-
1.19 (m, 1H); 13C NMR (67.9 MHz, CDCl3) δ 202.2, 106.6, 84.6,
76.7, 68.1, 41.9, 33.2, 33.0, 30.8, 25.2, 16.9; IR (neat) 3299,
2117, 1957, 1715, 1434 cm-1; MS (GC/MS) m/z 145 (M+ - 1),
131, 117, 105.
1-Vin ylid en e-2-(3-bu tyn yl)cycloh exa n e (31). Following
the representative procedure for desilylation of alkynyl allenes,
method B, 1-vinylidene-2-[4-(trimethylsilyl)-3-butynyl]cyclo-
hexane (62 mg, 0.27 mmol) was treated with TBAF to give
1-vinylidene-2-(3-butynyl)cyclohexane (31) (34 mg, 80%) as a
colorless oil. 1H NMR (270 MHz, CDCl3) δ 4.64 (dt, J ) 0.8,
3.4 Hz, 2H), 2.29-2.12 (m, 3H), 2.07-1.95 (m, 2H), 1.91 (t, J
) 2.7 Hz, 1H), 1.84-1.69 (m, 4H), 1.54-1.32 (m, 3H), 1.18-
1.05 (m, 1H); 13C NMR (67.9 MHz, CDCl3) δ 202.7, 105.0, 84.8,
75.1, 68.0, 38.2, 33.3, 32.4, 31.4, 27.4, 25.5, 16.3; IR (neat) 3306,
2117, 1958, 1250, 844 cm-1; MS (GC/MS) m/z 159 (M+ - 1),
145, 131, 117.
1-Vin ylid en e-2-[3-(t r im et h ylsilyl)-2-p r op yn yl]cyclo-
p en ta n e (34). A procedure reported by Inanaga20 was fol-
lowed for the preparation of compound 34. To a solution of
1-ethynyl-1-acetoxy-2-[3-(trimethylsilyl)-2-propynyl]cyclopen-
tane (245 mg, 0.935 mmol), tetrakis(triphenylphosphine)-
palladium (54 mg, 0.05 µm), and 2,4-dimethylpentan-3-ol
(0.144 mL, 1.03 mmol) in THF (5 mL) at 40 °C was added SmI2
(23.4 mL of a 0.1 M solution in THF, 2.34 mmol). After stirring
at this temperature for 9 h, the reaction mixture was poured
into saturated NH4Cl (30 mL) and filtered through pads of
Celite-Florisil. The filtrate was extracted with Et2O (3 × 30
mL). The combined organic layers were washed with brine
(30 mL) and dried over MgSO4. Removal of the solvent in
vacuo and purification by flash chromatography on silica gel
(eluting with hexane) furnished the title compound (48 mg,
73% based on recovered starting material) as a colorless oil
and 160 mg of recovered starting material. 1H NMR (270
MHz, CDCl3) δ 4.83-4.60 (m, 2H), 2.80-2.64 (m, 1H), 2.51-
2.36 (m, 3H), 2.18 (dd, J ) 8.9, 17.0 Hz, 1H), 2.05-1.91 (m,
1H), 1.83-1.69 (m, 1H), 1.68-1,42 (m, 2H), 0.14 (s, 9H); 13C
NMR (67.9 MHz, CDCl3) δ 202.1, 106.3, 106.0, 84.7, 77.1, 41.9,
32.6, 30.9, 25.0, 24.5, 0.1; IR (neat) 2175, 1958, 1249, 1022,
842 cm-1; MS (GC/MS) m/z 204, 189, 176, 161, 145, 130, 109.
8-Meth yl-6,7-n on a d ien -1-yn e (37). This compound was
prepared using the same procedure for the preparation of the
alkynyl allene 11. Magnesium chloride (1.9 g, 20 mmol), THF
(25 mL), and potassium (1.5 g, 38.4 mmol). 1-Chloro-5-
(trimethylsilyl)-4-pentyne (2.09 g, 12.0 mmol) in THF (10 mL),
copper(I) bromide (1.15 g, 8.02 mmol), lithium bromide (0.7 g,
7-(Cycloh exylid en e)-6-h ep t en -1-yn e (39). This com-
pound was prepared using the same procedure for the prepa-
ration of the alkynyl allene 11. Magnesium chloride (1.4 g,
14.7 mmol), THF (25 mL), and potassium (1.09 g, 27.9 mmol).
1-Chloro-5-(trimethylsilyl)-4-pentyne (1.95 g, 11.2 mmol) in
THF (10 mL), copper(I)bromide (1.0 g, 7.0 mmol), 1-ethynyl-
1-cyclohexanol (0.90 mL, 7.0 mmol), lithium bromide (0.61 g,
7.0 mmol), n-butyllithium (4.4 mL of a 1.6 M solution in
hexane, 7.0 mmol), and methanesulfonyl chloride (0.54 mL,
7.0 mmol). Purification by flash chromatography on silica gel
(eluting with pentane) provided 8-methyl-1-(trimethylsilyl)-
6,7-nonadien-1-yne (1.46 g, 85%). 1H NMR (270 MHz, CDCl3)
δ 4.97-4.88 (m, 1H), 2.25 (t, J ) 7.2, 2H), 2.16-1.98 (m, 6H),
1.67-1.46 (m, 8H), 0.13 (s, 9H); 13C NMR (67.9 MHz, CDCl3)
δ 198.5, 107.4, 102.7, 87.6, 84.3, 31.8, 28.3, 28.0, 27.5, 26.2,
19.1, 0.16; IR (neat) 2929, 2854, 2175, 1964, 1447, 1249, 840,
759 cm-1; MS (GC/MS) m/z 231, 203, 187, 173, 144, 131, 107,
79, 73; HRMS m/z (M+) calcd 246.1804, obsd 246.1810.
Following the representative procedure for desilylation of
alkynyl allenes, step B, 7-(cyclohexylidene)-1-(trimethylsilyl)-
6-hepten-1-yne (0.298 g, 1.21 mmol) was treated with TBAF
to afford 7-(cyclohexylidene)-6-hepten-1-yne (0.189 g, 90%)
as a colorless oil. 1H NMR (270 MHz, CDCl3) δ 4.97-4.89 (m,
1H), 2.21 (dt, J ) 2.6, 7.2, 2H), 2.12-1.99 (m, 6H), 1.92 (t, J
) 2.6 Hz, 1H), 1.68-1.43 (m, 8H); 13C NMR (67.9 MHz, CDCl3)
δ 198.4, 102.8, 87.5, 84.4, 68.2, 31.7, 28.1, 27.7, 27.5, 26.2, 17.6;
IR (neat) 3306, 2118, 1963, 1446, 1239 cm-1; MS (GC/MS) m/z
173, 159, 145, 131, 117, 105.
Rep r esen ta tive P r oced u r e for th e Allen ic [2 + 2 + 1]
Cycloa d d ition , Meth od A. 4-Meth ylid en e-2-(tr im eth yl-
silyl)bicyclo[3.3.0]oct-1-en -3-on e (2). To a solution of alky-
nyl allene 1 (150 mg, 0.84 mmol) in toluene (11 mL) and DMSO
(656 mg, 8.40 mmol) was added Mo(CO)6 (266 mg, 1.01 mmol).
The suspension was heated to 100 °C after which it became
homogeneous. The reaction was stirred at 100 °C for 3 h and
then cooled to room temperature and filtered through a pad
of silica gel, eluting with Et2O (50 mL). The Et2O was removed
in vacuo, and the crude reaction mixture was applied directly
to a chromatography column. Chromatography (hexanes then
5% Et2O/hex) gave 117 mg (68%) of cycloadduct 2 as a yellow
oil. 1H NMR (270 MHz, CDCl3) δ5.90 (dd, J ) 2.2, 1.8 Hz,
1H), 5.25 (br dd, J ) 1.5, 1.4 Hz, 1H), 3.31 (m, 1H), 2.64 (m,
1H), 2.58 (m, 1H), 2.29-2.14 (m, 1H), 2.11-2.01 (m, 2H), 1.23-
1.07 (m, 1H), 0.20 (s, 9H); 13C NMR (67.9 MHz, CDCl3) δ 201.7,
194.1, 147.5, 136.7, 113.6, 51.9, 28.8, 27.5, 26.1, -1.1; IR (neat)
2935, 1692, 1597, 1249 cm-1; MS (GC/MS) m/e 206 (M+), 191,
163, 135, 117.
7,7-Dim eth yl-6-h yd r oxyl-4-m eth ylid en e-2-(tr im eth yl-
silyl)bicyclo[3.3.0] oct-1-en -3-on e (4). Following the rep-
resentative procedure for the allenic [2 + 2 + 1] cycloaddition,
method A, after 20 h, cycloaddition of 4,4-dimethyl-5-hydroxy-
1-(trimethylsilyl)-6,7-octadien-1-yne (3) (60 mg, 0.27 mmol)
afforded the title compound (32 mg, 47%) as a colorless oil.

An Intramolecular Allenic [2 + 2 + 1] Cycloaddition
J . Org. Chem., Vol. 63, No. 19, 1998 6543
Min or isom er : 1H NMR (270 MHz, CDCl3) δ 6.09 (s, 1H), 5.34
(s, 1H), 3.89 (s, 2H), 2.54 (dd, J ) 23.0, 19.0 Hz, 2H), 1.62 (s,
1H), 1.21 (s, 6H), 0.2 (s, 9H); 13C NMR (67.9 MHz, CDCl3) δ
201.2, 191.4, 143.0, 139.0, 114.7, 77.2, 56.5, 45.9, 41.4, 29.2,
23.7, -1.3; IR (neat) 3431, 2174, 1682, 1647, 1591, 1092, 841
cm-1; MS (GC/MS) m/z 250, 235, 222, 207, 180, 160, 145, 117;
CI HRMS (M+ + 1) calcd: 251.1467, obsd: 251.1478. Ma jor
199.3, 183.9, 138.7, 138.3, 127.4, 51.1, 31.8, 29.5, 29.4, 29.2,
29.1, 27.0, 26.3, 26.1, 22.6, 14.1; IR (neat) 1695, 1654, 1623,
1458, 1325 cm-1; MS (GC/MS) m/z 232 (M+), 203, 189, 161,
147, 134; HRMS m/z (M+ + 1) calcd 233.1905, obsd 233.1906.
(E)-4-Octylid en ebicyclo[3.3.0]oct-1-en -3-on e (10): 1H
NMR (270 MHz, CDCl3) δ 6.49 (dt, J ) 1.8, 7.7 Hz, 1H), 6.03
(s, 1H), 3.35 (t, J ) 9.8 Hz, 1H), 2.70-2.46 (m, 2H), 2.33-2.04
(m, 5H), 1.50-1.10 (m, 11H), 0.86 (t, J ) 6.7, 3H); 13C NMR
(67.9 MHz, CDCl3) δ 198.2, 184.9, 139.2, 134.3, 126.0, 48.8,
31.7, 29.7, 29.4, 29.2, 29.1, 28.8, 25.9, 25.7, 22.6, 14.0; IR (neat)
1701, 1655, 1620, 1458 cm-1; MS (GC/MS) m/z 232 (M+), 203,
189, 161, 147, 134; HRMS m/z (M+ + 1) calcd 233.1905, obsd
233.1898.
1
isom er : H NMR (270 MHz, CDCl3) δ 5.94 (dd, J ) 1.7, 1.1
Hz, 1H), 5.51 (dd, J ) 1.2, 1.2 Hz, 1H), 3.58 (d, J ) 10.1 Hz,
1H), 3.41 (d, J ) 10.1 Hz, 1H), 2.72 (d, J ) 18.6 Hz, 1H), 2.47
(dd, J ) 1.5, 18.7 Hz, 1H), 2.17 (s, 1H), 1.19 (s, 3H), 1.11 (s,
3H), 0.20 (s, 9H); 13C NMR (67.9 MHz, CDCl3) δ 200.7, 185.7,
146.0, 139.2, 114.0, 82.0, 55.4, 43.4, 43.0, 28.2, 23.7, -1.2; IR
(neat) 3431, 2174, 1682, 1647, 1591, 1092 cm-1; MS (GC/MS)
m/z 250, 235, 222, 207, 180, 160, 145.
(Z)- a n d (E)-4-Ben zylid en ebicyclo[3.3.0]oct-1-en -3-on e
(12): Following the representative procedure for the allenic
[2 + 2 + 1] cycloaddition reaction Method A, after 11h,
cycloaddition of 8-phenyl-6,7-octadien-1-yne (11) (55 mg, 0.30
mmol) gave (Z)-4-benzylidenebicyclo[3.3.0]oct-1-en-3-one (7 mg,
12%) and (E)-4-benzylidenebicyclo[3.3.0]oct-1-en-3-one (37 mg,
58%). (Z)-4-Ben zylid en ebicyclo[3.3.0]oct-1-en -3-on e (12):
1H NMR (270 MHz, CDCl3) δ 7.98 (dd, J ) 1.7, 7.6 Hz, 2H),
7.41-7.18 (m, 3H), 6.66 (s, 1H), 6.07 (s, 1H), 3.59-3.48 (m,
1H), 2.76-2.48 (m, 2H), 2.32-2.06 (m, 3H), 1.40-1.23 (m, 1H);
13C NMR (67.9 MHz, CDCl3) δ 196.7, 183.3, 139.2, 134.8, 134.5,
130.7, 129.2, 128.0, 127.8, 52.8, 29.7, 26.3, 26.2; IR (neat) 1682,
1614, 1450, 1173 cm-1; MS (GC/MS) m/z 210, 181, 167, 154,
141; HRMS m/z (M+ + 1) calcd 211.1123, obsd 211.1123.
7,7-Dim eth yl-6-[(m eth oxym eth yl)oxy]-4-m eth ylid en e-
2-(tr im eth ylsilyl)bicyclo[3.3.0]oct-1-en -3-on e (6). Follow-
ing the representative procedures for the allenic [2 + 2 + 1]
cycloaddition reactions, method A, after 20 h, cycloaddition of
4,4-dimethyl-5-[(methoxymethyl)oxy]-1-(trimethylsilyl)-6,7-oc-
tadien-1-yne (32 mg, 0.12 mmol) gave 7,7-dimethyl-6-[(meth-
oxymethyl)oxy]-4-methylidene-2-(trimethylsilyl)bicyclo[3.3.0]-
oct-1-en-3-one as a mixture of two diastereomers (9.5 mg, 54%
based on recovered starting material) together with 16 mg of
starting material. Ma jor isom er : 1H NMR (270 MHz, CDCl3)
δ 5.97 (dd, J ) 1,2, 1.8 Hz, 1H), 5.47 (t, J ) 1.2 Hz, 1H), 4.74
(dd, J ) 6.7, 10.9 Hz, 2H), 5.65 (d, J ) 9.1 Hz, 1H), 3.42 (s,
3H), 3.35 (d, J ) 9.1 Hz, 1H), 2.70 (d, J ) 17.8, 1H), 2.46 (dd,
J ) 1.3, 17.7 Hz, 1H), 1.22 (s, 3H), 1.09 (s, 3H), 0.21 (s, 9H);
13C NMR (67.9 MHz, CDCl3) δ 200.6, 185.9, 145.9, 138.7, 114.5,
96.9, 87.4, 55.8, 55.2, 43.6, 43.5, 28.9, 24.6, -1.1; IR (neat)
1692 1599, 1149, 1040 cm-1; MS (GC/MS) m/z 294, 279, 249,
221, 219, 193, 147; HRMS (M+ + 1) calcd 295.1729 obsd
295.1740. Min or isom er : 1H NMR (270 MHz, CDCl3) δ 5.91
(d, J ) 3.8 Hz, 1H) 4.79 (d, J ) 6.9 Hz, 1H), 4.69 (d, J ) 6.7
Hz, 1H), 3.93 (d, J ) 3.6 Hz, 1H), 3.42 (s, 3H), 2.90 (s, 2H),
2.70 (d, J ) 16.8 Hz, 1H), 2.45 (d, J ) 16.4 Hz, 1H), 1.03 (s,
3H), 0.99 (s, 3H), 0.24 (s, 9H); 13C NMR (67.9 MHz, CDCl3) δ
209.0, 175.2, 141.6, 138.6, 123.6, 96.4, 78.9, 55.6, 39.0, 38.8,
1
(E)-4-Ben zylid en ebicyclo[3.3.0]oct-1-en -3-on e (12): H
NMR (270 MHz, CDCl3) δ 7.57-7.52 (m, 2H), 7.43-7.30 (m,
4H), 6.14 (s, 1H), 3.76 (t, J ) 9.7 Hz, 1H), 2.78-2.54 (m, 2H),
2.43-2.34 (m, 1H), 2.24-1.96 (m, 2H), 1.16-1.00 (m, 1H); 13
C
NMR (67.9 MHz, CDCl3) δ 198.8, 185.0, 137.7, 134.9, 130.5,
130.2, 129.0, 128.6, 125.7, 49.5, 28.0, 25.9, 24.9; IR (neat) 1694,
1614, 1449, 1181 cm-1; MS (GC/MS) m/z 210, 181, 167, 154,
141; HRMS m/z (M+ + 1) calcd 211.1123, obsd 211.1122.
Rep r esen ta tive P r oced u r e for th e Allen ic [2 + 2 + 1]
Cycloa d d ition , Meth od B. 4-Hep tyl-2-(tr im eth ylsilyl)-
bicyclo[4.3.0]n on a -1,5-d ien -3-on e (14), (E)- a n d (Z)-4-
oct ylid e n e -2-(t r im e t h ylsilyl)b icyclo[3.3.0]oct -1-e n -3-
on e (15). To a solution of 1-(trimethylsilyl)-6,7-pentadecadien-
1-yne-hexacarbonyl dicobalt complex (13) (60 mg, 0.11 mmol)
in CH2Cl2 (5 mmol) under air at 40 °C was added DMSO (24
µL, 0.34 mmol). The reaction mixture was stirred at 40 °C
for 22 h and then passed through a small plug of silica gel,
eluting with EtOAc/hexane (1:1). The solution was concen-
trated in vacuo and the residue purified by flash chromatog-
raphy on silica gel by eluting with 2% EtOAc/hexane to furnish
the enone products (20 mg, 60%) as a mixture of three products
(ratios based upon 1H NMR). The separation of pure 14, 15-
E, and 15-Z was effected by HPLC using a silica column with
0.75 EtOAc/hexanes used as the eluent.
36.6, 26.9, 22.8, -0.6; IR (neat) 1694, 1556, 1149, 1038 cm-1
;
MS (GC/MS) m/z 294, 249, 233, 219, 190, 162, 134; HRMS m/z
(M+ + 1) calcd 295.1729 obsd 295.1722.
4-Met h ylid en e-2-(t r im et h ylsilyl)b icyclo[4.3.0]n on -1-
en -3-on e (8). To a solution of alkynyl allene 7 (76 mg, 0.4
mmol) in benzene (7 mL) and DMSO (310 mg, 4.0 mmol) was
added Mo(CO)6 (125 mg, 0.48 mmol). The suspension was
heated to 80 °C after which it became homogeneous. The
reaction was stirred at 80 °C for 18 h and then cooled to room
temperature and filtered through a pad of silica gel eluting
with Et2O (25 mL). The ether was removed in vacuo and the
crude reaction mixture applied directly to column chromatog-
raphy. Chromatography (5% EtOAc/hex) gave 38.4 mg recov-
ered alkynyl allene 7 and 13 mg (15%, 30% based upon
recovered starting material) of cycloadduct 8 as a yellow oil.
1H NMR (270 MHz, CDCl3) δ5.91 (dd, J ) 1.7, 1.0 Hz, 1H),
5.23 (t, J ) 1.2 Hz, 1H), 3.00 (m, 1H), 2.29-2.17 (m, 2H), 2.06-
1.98 (m, 1H), 1.89-1.83 (m, 1H), 1.62-1.48 (m, 1H), 1.41-
1.07 (m, 3H), 0.24 (s, 9H); 13C NMR (67.9 MHz, CDCl3) δ 200.0,
186.2, 147.5, 137.2, 113.7,46.8, 33.7, 31.3, 27.0, 25.0, -0.3; IR
(neat) 1690, 1647, 1579 cm-1; MS (GC/MS) m/e 220 (M+), 205,
189, 176, 161, 149.
(Z)- a n d (E)-4-Oct ylid en eb icyclo[3.3.0]oct -1-en -3-on e
(10). Following the representative procedure for the allenic
[2 + 2 + 1] cycloaddition, method A. A mixture of 6,7-
pentadecadien-1-yne (9) (63 mg, 0.31 mmol), molybdenum
carbonyl (122 mg, 0.46 mmol), and DMSO (219 µL, 3.1 mmol)
in toluene (3 mL) was heated at 110 °C for 18 h to furnish
(Z)-4-octylidenebicyclo[3.3.0]oct-1-en-3-one (18 mg, 25%) and
(E)-4-octylidenebicyclo[3.3.0]oct-1-en-3-one (36 mg, 50%). The
isomers 10-E and 10-Z were separated using column chroma-
tography(3%ether/hexanes). (Z)-4-Octylid en ebicyclo[3.3.0]-
oct-1-en -3-on e (10): 1H NMR (270 MHz, CDCl3) δ 5.98 (s, 1H),
5.90 (t, J ) 7.5 Hz, 1H), 3.33-3.23 (m, 1H), 2.74 (q, J ) 7.1
Hz, 2H), 2.67-2.43 (m, 2H), 2.18-2.01 (m, 3H), 1.41-1.10 (m,
11H), 0.86 (t, J ) 6.6 Hz, 3H); 13C NMR (67.9 MHz, CDCl3) δ
(Z)-4-Octylid en e-2-(tr im eth ylsilyl)bicyclo[3.3.0]oct-1-
en -3-on e (15): 1H NMR (270 MHz, CDCl3) δ 5.86 (dt, J ) 1.6,
7.5 Hz, 1H), 3.25 (dd, J ) 6.9, 11.7 Hz, 1H), 2.83-2.43 (m,
4H), 2.16-1.94 (m, 3H), 1.42-1.03 (m, 11H), 0.85 (t, J ) 6.9
Hz, 3H), 0.19 (s, 9H); 13C NMR (67.9 MHz, CDCl3) δ 203.2,
192.4, 138.9, 138.3, 137.5, 53.1, 31.9, 31.7, 29.7, 29.4, 29.3, 27.6,
27.1, 26.5, 22.7, 14.2, -0.97; IR (neat) 1685, 1646, 1600, 1218
cm-1; MS (GC/MS) m/z 304 (M+), 289, 233, 220, 178, 161;
HRMS m/z (M+ + 1) calcd 305.2301, obsd 305.2284.
4-Hep tyl-2-(tr im eth ylsilyl)bicyclo[4.3.0]n on a -1,5-d ien -
1
3-on e (14): H NMR (270 MHz, CDCl3) δ 5.97 (t, J ) 4.0 Hz,
1H), 2.80-2.63 (m, 3H), 2.25 (q, J ) 5.0 Hz, 2H), 1.87-1.72
(m, 2H), 1.70-1.56 (m, 2H), 1.15-1.23 (m, 10H), 0.84 (t, J )
6.9 Hz, 3H), 0.21 (s, 9H); 13C NMR (67.9 MHz, CDCl3) δ 212.6,
176.2, 142.7, 137.2, 125.1, 47.9, 31.9, 30.2, 29.9, 29.2, 27.5, 25.7,
25.2, 22.7, 22.6, 14.2, -0.4; IR (neat) 1687, 1553 cm-1; MS (GC/
MS) m/z 304 (M+), 289, 206, 190, 147, 129.
(E)-4-Octylid en e-2-(tr im eth ylsilyl)bicyclo[3.3.0]oct-1-
en -3-on e (15): 1H NMR (270 MHz, CDCl3) δ 6.42 (dt, J ) 2.0,
7.7 Hz, 1H), 3.28 (dd, J ) 7.5, 12.1 Hz, 1H), 2.72-2.46 (m,
2H), 2.31-2.00 (m, 5H), 1.49-1.38 (m, 2H), 1.31-1.07 (m, 9H),
0.86 (t, J ) 6.9 Hz, 3H), 0.20 (s, 9H); 13C NMR (67.9 MHz,
CDCl3) δ 201.9, 192.8, 139.7, 136.7, 133.3, 50.7, 31.9, 29.9, 29.5,
29.2, 29.2, 29.0, 27.0, 26.2, 22.7, 14.2, -1.0; IR (neat) 1694,

6544 J . Org. Chem., Vol. 63, No. 19, 1998
Brummond et al.
1657, 1600, 839 cm-1; MS (GC/MS) m/z 304 (M+), 289, 233,
220, 189, 161, 131.
127.4, 85.0, 52.5, 44.5, 42.0, 38.1, 33.6, 30.2, 29.5, 26.1, 25.8,
20.0, 18.2, -3.7, -4.4; IR (neat) 1704, 1580, 1462, 1199, 1100,
1007 cm-1; MS (GC/MS) m/z 346 (M+), 331, 289, 233, 214, 172,
158, 118.
Rep r esen ta tive P r oced u r e for th e Allen ic [2 + 2 + 1]
Cycloa d d ition , Meth od C. To a solution of 1-(trimethylsi-
lyl)-6,7-pentadecadien-1-yne-hexacarbonyldicobalt complex
(13) (69 mg, 0.12 mmol) in CH2Cl2 (0.5 mL) was added
trimethylamine N-oxide (56 mg, 0.75 mmol) at room temper-
ature. The reaction mixture was stirred for 80 min and then
passed through a small plug of silica gel, eluting with EtOAc/
hexane (1:1). The solution was concentrated in vacuo and the
residue purified by flash chromatography on silica gel, eluting
with 2% EtOAc/hexane to furnish the enone (23 mg, 62%) as
a mixture of isomers (see Table 2, entry 4).
Rep r esen ta tive P r oced u r e for th e Allen ic [2 + 2 + 1]
Cycloa d d ition , Meth od D. To a degassed solution of 1-(tri-
methylsilyl)-6,7-pentadecadien-1-yne (16) (30 mg, 0.11 mmol)
in benzene (2 mL) was added dicobaltoctacarbonyl (45 mg, 0.13
mmol) at room temperature. After stirring for 3 h, the TLC
showed complete complexation of the alkyne, DMSO (24 µL,
0.33 mmol) was then added, and the mixture was stirred in
air at 40 °C for 28 h. The reaction mixture was passed through
a small plug of silica gel, eluting with EtOAc/hexane (1:1). The
solution was concentrated in vacuo and flash chromatography
on silica gel, eluting with 2% EtOAc/hexane to furnish the
enone (11 mg, 33%) as a mixture of isomers (see Table 2, entry
5).
Rep r esen ta tive P r oced u r e for th e Allen ic [2 + 2 + 1]
Cycloa d d ition , Meth od E. To a solution of Cp2ZrCl2 (53 mg,
0.18 mmol) in THF (2 mL) at -78 °C under argon was added
n-butyllithium (0.23 mL of a 1.6 M solution in hexane, 0.37
mmol). Upon completion of addition, stirring was continued
at -78 °C for 1 h, and 1-(trimethylsilyl)-6,7-pentadecadien-1-
yne (16) (48 mg, 0.17 mmol) in THF (0.5 mL) was added. The
reaction mixture was warmed to room temperature over 2 h
and then stirred for an additional 4 h, whereupon it was
transferred to a sealed tube and cooled to 0 °C. The solution
was degassed and flushed with CO; this process was repeated
three times then the solution was placed under CO pressure
(20 psi). The reaction mixture was stirred at 0 °C for 2 h and
quenched with 3 M HCl (20 mL) and pentane (20 mL). The
aqueous layer was extracted with pentane (3 × 20 mL) and
the combined extracts were washed with NaHCO3 (20 mL) and
brine (20 mL) and then dried over MgSO4. Removal of the
solvent in vacuo and purification by flash chromatography on
silica gel (eluting with 2% EtOAc/hexane) afforded the enone
products 14 and 15-E (25 mg, 48%).
6-Bu tylbicyclo[4.3.0]n on a -1,5-d ien -3-on e (21). Follow-
ing the experimental procedure for the allenic [2 + 2 + 1]
cycloaddition reaction, method A, after 16 h, cycloaddition of
3-butyl-1,2-octadien-7-yne (20) (54 mg, 0.33 mmol) afforded
the title compound 21 (38 mg, 60%) as a colorless oil. 1H NMR
(270 MHz, CDCl3) δ 5.83 (s, 1H), 2.86 (s, 2H), 2.60 (t, J ) 6.3
Hz, 2H), 2.21-2.08 (m, 4H), 1.80 (quin, J ) 6.2 Hz, 2H) 1.47-
1.22 (m, 4H), 0.89 (t, J ) 7.2 Hz, 3H); 13C NMR (67.9 MHz,
CDCl3) δ 205.5, 172.3, 141.0, 131.1, 126.1, 37.6, 34.7, 29.6, 28.5,
26.1, 22.6, 22.4, 13.9; IR (neat) 2929, 2859, 1699, 1671, 1581,
1455, 1246, 841 cm-1; MS (GC/MS) m/z 190 (M+), 175, 161,
147, 119, 105, 91, 77, 65, 41; HRMS m/z (M+) calcd 190.1358,
obsd 190.1358.
Ta ble 3, En tr y 4. Following the experimental procedure
for the allenic [2 + 2 + 1] cycloaddition reaction, method A,
after 15 h, 1-vinylidene-2-(3-butynyl)cyclopentane (41 mg, 0.28
mmol) gave two isomeric products (major isomer 26: 31 mg,
64%; minor isomer 27: 4.6 mg, 9%). Major isomer 26: 1H
NMR (270 MHz, CDCl3) δ 5.78 (s, 1H), 2.83-2.72 (m, 3H),
2.47-2.23 (m, 4H), 2.18-2.09 (m, 1H), 2.07-1.98 (m, 1H),
1.91-1.81 (m, 1H), 1.72-1.53 (m, 1H), 1.37-1.03 (m, 2H); 13
C
NMR (67.9 MHz, CDCl3) δ 206.1, 172.8, 148.2, 128.4, 125.0,
42.7, 37.4, 33.7, 29.4, 29.3, 26.4, 24.1; IR (neat) 1689, 1654,
1574, 1167, 922, 832 cm-1; MS (GC/MS) m/z 174 (M+), 159,
146, 131, 117; HRMS m/z (M+) calcd 174.1045, obsd 174.1048.
Minor isomer 27: 1H NMR (270 MHz, CDCl3) δ 5.96 (s, 1H),
5.81 (s, 1H), 5.17 (s, 1H), 2.62-2.52 (m, 2H), 2.41-2.31 (m,
1H), 2.12-1.97 (m, 2H), 1.90-1.62 (m, 6H); 13C NMR (67.9
MHz, CDCl3) δ 198.5, 188.3, 154.4, 124.0, 111.4, 62.2, 46.2,
40.3, 36.2, 33.7, 27.5, 26.9; IR (neat) 1694, 1651, 1621, 1453,
1137 862 cm-1; MS (GC/MS) m/z 174 (M+), 159, 146, 131, 117;
HRMS m/z (M+) calcd 174.1045, obsd 174.1038.
Ta ble 3, En tr y 5. Following the experimental procedure
for the allenic [2 + 2 + 1] cycloaddition, Method A, after 12 h,
1-vinylidene-2-[4-(trimethylsilyl)-3-butynyl]cyclopentane (28)
(26 mg, 0.11 mmol) gave the enone 29 (15 mg, 50%); 1H NMR
(270 MHz, CDCl3) δ 2.96 (dt, J ) 17.0, 3.0 Hz, 1H), 2.77 (s,
2H), 2.50-2.25 (m, 4H), 2.22-2.01 (m, 2H), 1.94-1.80 (m, 1H),
1.74-1.56 (m, 1H), 1.41-1.06 (m, 2H), 0.22 (s, 9H); 13C NMR
(67.9 MHz, CDCl3) δ 210.1, 178.5, 147.2, 135.4, 130.0, 42.3,
38.0, 33.8, 29.7, 29.6, 27.4, 24.1, -0.4; IR (neat) 1957, 1889,
1664, 1542, 890 cm-1; MS (GC/MS) m/z 246 (M+), 231, 202,
187, 155, 129; HRMS m/z (M+) calcd 246.1440, obsd 246.1442.
Ta ble 3, En tr y 6. Following the experimental procedure
for the allenic [2 + 2 + 1] cycloaddition, Method A, after 15 h,
2-(3-butynyl)-1-vinylidene-cyclohexane (31) (34 mg, 0.21 mmol)
gave two isomeric products (major isomer 32: 20 mg, 50%;
minor isomer 33: 5 mg, 12%); major isomer: 1H NMR (270
MHz, CDCl3) δ 5.82 (s, 1H), 2.84 (s, 2H), 2.73 (dt, J ) 4.3,
17.0 Hz, 1H), 2.49-2.37 (m, 2H), 2.22-2.12 (m, 1H), 2.04-
1.74 (m, 5H), 1.48-1.20 (m, 3H), 1.05 (dq, J ) 3.1, 12.5 Hz,
1H); 13C NMR (67.9 MHz, CDCl3) δ 205.7, 172.4, 142.5, 129.6,
126.4, 37.8, 37.3, 34.6, 31.1, 29.5, 26.6, 25.6, 25.3; IR (neat)
1698, 1673, 1579, 1210, 841 cm-1; MS (GC/MS) m/z 188 (M+),
173, 160, 132, 117; HRMS m/z (M+ + 1) calcd 188.1201, obsd
188.1200. minor isomer: 1H NMR (270 MHz, CDCl3) δ 5.96
(s, 1H), 5.84 (s, 1H), 5.46 (s, 1H), 2.85-2.70 (m, 1H), 2.65-
2.50 (m, 1H), 2.30-2.11 (m, 1H), 1.98-1.83 (m, 2H), 1.77-
1.39 (m, 7H), 1.29-1.19 (m, 1H); 13C NMR (67.9 MHz, CDCl3)
δ 198.3, 191.2, 152.2, 124.5, 112.2, 53.5, 39.4, 30.8, 27.0, 24.8,
24.4, 22.1, 19.5; IR (neat) 1701, 1618, 1118 cm-1; MS (GC/MS)
m/z 188 (M+), 173, 160, 131, 117; HRMS m/z (M+ + 1) calcd
188.1201, obsd 188.1191.
Ta ble 3, En tr y 7 (35). Following the representative
procedures for the allenic [2 + 2 + 1] cycloaddition reactions,
method A, after 5 h, cycloaddition of 1-vinylidene-2-[3-(trim-
ethylsilyl)-2-propynyl]cyclopentane (34) (15.5 mg, 0.076 mmol)
afforded the title compound 35 as a colorless oil (11.7 mg, 66%).
1H NMR (270 MHz, CDCl3) δ 3.30-3.18 (m, 1H), 2.97 (dd, J
) 6.3, 18.8 Hz, 1H), 2.76 (s, 2H), 2.42-2.22 (m, 3H), 2.17-
1.99 (m, 3H), 1.25-1.07 (m, 1H), 0.2 (s, 9H); 13C NMR (67.9
MHz, CDCl3) δ 212.2, 199.3, 157.5, 135.7, 129.7, 55.7, 36.2,
32.8, 30.7, 27.7, 23.2, -1.1; IR (neat) 1697, 1676, 1559, 921
cm-1; MS (GC/MS) m/z 232, 217, 189, 161, 143, 128.
6-Bu tylbicyclo[4.3.0]n on a -1,5-d ien -3-on e (21). Follow-
ing the experimental procedure for the allenic Pauson-Khand
cycloaddition reaction, method A, after 24 h, cycloaddition of
3-butyl-1-(trimethylsilyl)-1,2-octadiene-7-yne (22) (23 mg, 0.098
mmol) afforded the title compound 21 (11 mg, 59%) as a
colorless oil.
En on e 24. Following the experimental procedure for the
allenic [2 + 2 + 1] cycloaddition, method A, after 19 h,
cycloaddition of [1R*,2R*,3R*]-1-(tert-butyldimethylsilyloxy)-
2-(1-methylallenyl)-3-(2-propynyl)-5,5-dimethylcyclopentane (23)
(19 mg, 0.06 mmol) gave the enone 24 (5 mg, 24%, 42% based
on recovered starting material). 1H NMR (270 MHz, CDCl3)
δ 5.86 (s, 1H), 3.83 (d, J ) 5.1 Hz, 1H), 2.86 (d, J ) 4.6 Hz,
2H), 2.76-2.52 (m, 3H), 1.87 (s, 3H), 1.76-1.60 (m, 2H), 1.28-
1.18 (m, 1H), 0.95 (s, 6H), 0.90 (s, 9H), 0.05 (s, 3H), 0.01 (s,
3H); 13C NMR (67.9 MHz, CDCl3) δ 205.5, 170.7, 135.8, 131.7,
4-(1,1-Dim et h ylm et h ylid en e)b icyclo[3.3.0]oct -1-en -3-
on e (38): Following the representative procedures for the
allenic [2 + 2 + 1] cycloaddition reaction, method A, after 10
h, cycloaddition of 8-methyl-6,7-nonadien-1-yne (37) (45 mg,
0.336 mmol) gave 4-(1,1-dimethylmethylidene)bicyclo[3.3.0]oct-
1-en-3-one (38) (32 mg, 59%). 1H NMR (270 MHz, CDCl3) δ
5.97(s, 1H), 3.33(t, J ) 9.6 Hz, 1H), 2.66-2.40 (m, 2H), 2.32-
2.20 (m, 4H), 2.12-2.01 (m, 2H), 1.89 (s, 3H), 1.24-1.06 (m,

An Intramolecular Allenic [2 + 2 + 1] Cycloaddition
J . Org. Chem., Vol. 63, No. 19, 1998 6545
1H); 13C NMR (67.9 MHz, CDCl3) δ 198.7, 181.3, 145.1, 133.8,
127.5, 50.4, 29.6, 25.7, 25.4, 24.4, 19.6; IR (neat) 1682, 1632,
1446, 1067 cm-1; MS (GC/MS) m/z 162, 147, 134, 119, 106;
HRMS m/z (M+) calcd 162.1045 obsd 162.1047.
202, 174, 160, 147, 131, 117; CI HRMS (M+ + 17) calcd:
219.1623 obsd: 219.1622.
Ack n ow led gm en t. We gratefully acknowledge the
financial support provided by the National Science
Foundation-EPSCoR and the National Institutes of
Health (GM54161).
4-Cycloh exa ylid en eb icyclo[3.3.0]oct -1-en -3-on e (40).
Following the representative procedures for the allenic [2 + 2
+ 1] cycloaddition reactions, method A, after 10 h, cycloaddi-
tion of 8-phenyl-6,7-octadien-1-yne (39) (46 mg, 0.264 mmol)
gave 4-cyclohexaylidenebicyclo[3.3.0]oct-1-en-3-one (40) (31
mg, 58% yield). 1H NMR (270 MHz, CDCl3) δ 5.98 (s, 1H),
3.34 (dd, J ) 7.9, 11.1 Hz, 1H), 3.10-2.90 (m, 2H), 2.65-2.40
(m, 2H), 2.32-2.18 (m, 3H), 2.14-1.99 (m, 2H), 1.78-1.50 (M,
6H), 1.25-1.09 (M, 1H); 13C NMR (67.9 MHz, CDCl3) δ 199.3,
181.4, 153.2, 130.8, 127.9, 50.0, 34.4, 30.1, 28.5, 28.4, 28.2, 26.4,
25.7, 25.4; IR (neat) 1680, 1620, 994 cm-1; MS (GC/MS) m/z
Su p p or t in g In for m a t ion Ava ila b le: 1H NMR and 13C
NMR of all alkynyl allenes and cycloadducts are available (90
pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
J O980548C