[2+2+1] Cycloadditions of ynol ethers. The synthesis of iron complexes of 3-alkoxycyclopentadienones

Article abstract of DOI:10.1016/S0040-4039(01)01473-3

This Letter reports the synthesis of iron complexes of 3-oxocyclopentadienones from ynol ether-alkyne [2+2+1] cycloaddition reactions as well as the use of 3-alkoxycyclopentadienones in subsequent cycloaddition reactions.

Full text of DOI:10.1016/S0040-4039(01)01473-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 6987–6990
[2+2+1] Cycloadditions of ynol ethers. The synthesis of iron
complexes of 3-alkoxycyclopentadienones
Jason E. Imbriglio and Jon D. Rainier*
Department of Chemistry, The University of Arizona, Tucson, AZ 85721, USA
Received 27 July 2001; revised 8 August 2001; accepted 9 August 2001
Abstract—This Letter reports the synthesis of iron complexes of 3-oxocyclopentadienones from ynol ether–alkyne [2+2+1]
cycloaddition reactions as well as the use of 3-alkoxycyclopentadienones in subsequent cycloaddition reactions. © 2001 Elsevier
Science Ltd. All rights reserved.
In spite of their vast synthetic potential, cyclopenta-
dienones have not been widely utilized in organic syn-
thesis. This has been due, in part, to the lack of
synthetically useful cyclopentadienones that are avail-
able and to the enhanced reactivity of cyclopenta-
dienones lacking substitution.1
nificant potential in organic synthesis. Outlined herein
are our preliminary results in this area.
Our initial investigations explored unsubstituted ynol
ethers 2, 5, and 8 having 2-, 3-, and 4-carbon tethers
between the alkyne and the ynol ether, respectively.
These were synthesized in two steps from the corre-
sponding alkynols (Table 1, entries 1–3). Namely, expo-
sure of the alkynols to KH and trichloroethylene
resulted in the formation of the corresponding
dichlorovinyl ethers (e.g. 1, 4, and 7). Upon treatment
with BuLi, vinyl ethers 1, 4, and 7 were converted into
ynol ethers 2, 5, and 8, respectively, after trapping of
the intermediate dianion with TMSCl.7,8 With 2, 5, and
8 in hand, we exposed them to thermal cycloaddition
conditions in the presence of Fe(CO)5. This protocol
resulted in the isolation of tricarbonyliron cyclopenta-
dienone complexes 3, 6, and 9 in relatively low yield.9
One solution to the reactivity problem has involved the
protection of the dienone as the corresponding transi-
tion metal complex.2–4 While not proven in a general
sense, metal coordination also presents one with the
possibility of carrying out stereoselective reactions on
functionality pendant to the cyclopentadienone
complex.5
From an interest in the use of cyclopentadienones in
the synthesis of heterocyclic natural products, we have
become fascinated with cyclopentadienone metal com-
plexes that have heteroatom substitution at the 3-posi-
tion. As an illustration of this, we recently
demonstrated that cobalt and iron complexes of 3-
aminocyclopentadienones could be generated from
ynamine–alkyne [2+2+1] cycloaddition reactions.6 Fol-
lowing oxidative decomplexation of the metal, we also
demonstrated that the free cyclopentadienones could be
induced to undergo chemo- and stereoselective cycload-
dition reactions with dienophiles.
While pleased that we were able to generate 3-alkoxy-
cyclopentadienones 3, 6, and 9, we were not satisfied with
the efficiency of the [2+2+1] cycloaddition reaction.
From the hypothesis that the ground state conforma-
tion of 3, 6, and 9 was responsible for the low cycload-
dition yields,10 we turned to the cycloaddition of the
conformationally restricted aryl ynol ether 11 (Table 1,
entry 4). To our delight, the cycloaddition of 11 pro-
vided iron cyclopentadienone complex 1215 in 67% yield
in two steps from dichlorovinyl ether 10.
As a continuation of these studies, we have recently
become interested in the analogous [2+2+1] cycloaddi-
tion reactions of ynol ethers with pendant alkynes. If
successful, we believed that the 3-alkoxycyclopenta-
dienone products from these reactions would have sig-
To further demonstrate the importance of ynol ether
conformation on the cycloaddition reaction, we exam-
ined gem-dimethyl substituted ynol ether 14 (Table 1,
entries 5 and 6). When 14 was subjected to the same
conditions that we had used for the other substrates
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01473-3

6988
J. E. Imbriglio, J. D. Rainier / Tetrahedron Letters 42 (2001) 6987–6990
Table 1.
MLn
TMS
TMS
R
R
R'
O
Fe(CO)5
Cond's
1. KH, TCE
O
OH
O
2. BuLi; TMSCl
n
R
n
R'
TMS
R'
n
TMS
Enol ether
Yield
59%a
Ynol ether
Yield
Cyclopentadienone Cond'sc Yield
Entry
1
Fe(CO)3
TMS
O
Cl
O
TMS
O
37%d
24%d
O
-----
-----
-----
A
A
Cl
TMS
1
2
3
TMS
Fe(CO)3
TMS
Cl
O
O
TMS
TMS
O
2
3
54%a
47%a
O
Cl
TMS
4
7
5
6
Fe(CO)3
TMS
Cl
O
O
TMS
O
21%d
A
A
O
Cl
TMS
TMS
TMS
8
9
Fe(CO)3
TMS
Cl
O
O
O
4
57%a
67%d
-----
Cl
Cl
O
TMS
10
11
12
TMS
Fe(CO)3
TMS
Cl
O
O
TMS
O
83%b
83%b
-----
-----
48%
71%
5
6
A
B
O
TMS
TMS
13
13
14
14
15
15
ayield from the corresponding alkynol
byield is for two steps from 2,2-dimethyl-pent-4-yn-1-ol
cconditions: A: Fe(CO)5, PhCH3, 130 °C; B Fe(CO)5, PhCH3, 130 °C, alumina
dyield is for two steps from the corresponding dichloroenol ether
(i.e. Fe(CO)5, PhCH3, and 130°C), we isolated 1515 in a
disappointing 48% yield. In related Pauson Khand
cycloadditions of heteroatom bearing substrates, Smit
and Caple had found that alumina had dramatic effects
on the efficiency of the reaction.11 With the hope of
obtaining similar results, we included alumina in the
reaction of 14 with Fe(CO)5. We were pleased to isolate
cyclopentadienone complex 15 in 71% yield.12
decomplexation of 3, 6, 12, and 15 using trimethyl-
amine-N-oxide (TMANO) and the use of the resulting
3-alkoxycyclopentadienones in cycloaddition reactions
with alkynes is depicted in Table 2.15 In contrast to the
cycloadditions of 3-aminocyclopentadienones, the
cycloadditions of 3-alkoxycyclopentadienone with ethyl
propiolate gave mixtures of isomeric aromatic products
(entries 2–4). As expected, the major product had the
ester and ether substituents para to one another.13 As
had been our experience with the 3-aminocyclopenta-
dienone cycloadditions, the initial bicyclo[2.2.1]-
heptenone adducts were not observed. To the best of
our knowledge, these experiments represent the first
successful examples of the use of 3-alkoxycyclopenta-
dienones in cycloaddition reactions.14
Having established that ynol ether [2+2+1] cycloaddi-
tion reactions in the presence of Fe(CO)5 lead to the
generation of iron complexes of 3-alkoxycyclopenta-
dienones, we set out to demonstrate the utility of
metal-free 3-alkoxycyclopentadienones through their
use in cycloaddition reactions with dienophiles. The

J. E. Imbriglio, J. D. Rainier / Tetrahedron Letters 42 (2001) 6987–6990
6989
Table 2.
O
TMS
TMS
R"
R
O
R
TMANO
Dienophile
O
Metal
Cycloadduct
O
Complex
R'
PhH, 80°C
n
TMS
R'
R'"
TMS
n
Entry Complex Dienophile
Cycloadduct(s)
TMS
Ratiob
Yield
42%
CO2Me
O
-----
3:1
1
2
3
6
DMAD
16
CO2Me
TMS
TMS
TMS
TMS
TMS
O
H
O
CO2Et
17a
18
60%
ethyl propiolate
CO2Et
H H
TMS
TMS
O
O
CO2Et
19
20
12
3:1
3:1
70%
63%
3
4
ethyl propiolate
ethyl propiolate
CO2Et
TMS
TMS
TMS
TMS
O
CO2Et
O
21
22
15
CO2Et
TMS
TMS
aarrows depict observed nOe enhancements that were used to assign regioselectivity
bratio of para product to meta product as determined by 1H NMR
In summary, we have found that ynol ethers undergo
[2+2+1] cycloaddition reactions with pendant alkynes
when subjected to Fe(CO)5. We have also found that
3-alkoxycyclopentadienones undergo cycloaddition
reactions with ethyl propiolate. Our current efforts in
this area are focused on the optimization of the reac-
tions that we have discovered, the use of 3-heterosubsti-
tuted iron cyclopentadienones in stereoselective
reactions and the use of 3-heterocyclopentadienones in
the synthesis of biologically active heterocycles.
2. Co–cyclopentadienone complexes: (a) McDonnell Bush-
nell, L. P.; Evitt, E. R.; Bergman, R. G. J. Organomet.
Chem. 1978, 157, 445; (b) Gesing, E. R. F.; Tane, J. P.;
Vollhardt, K. P. C. Angew. Chem., Int. Ed. 1980, 19,
1023.
3. Fe–cyclopentadienone complexes: (a) Pearson, A. J.;
Dubbert, R. A. J. Chem. Soc., Chem. Commun. 1991,
371; (b) Kno¨lker, H.-J.; Heber, J.; Mahler, C. H. Synlett
1992, 1002; (c) Pearson, A. J.; Shively, R. J., Jr.; Dub-
bert, R. A. Organometallics 1992, 11, 4096; (d) Pearson,
A. J.; Shively, R. J., Jr. Organometallics 1994, 13, 578; (e)
Brookhart, M.; Chandler, W. A.; Pfister, A. C.; Santini,
C. C.; White, P. S. Organometallics 1992, 11, 1263.
4. Ru–cyclopentadienone complexes: (a) Mauthner, K.;
Mereiter, K.; Schmid, R.; Kirchner, K. Organometallics
1994, 13, 5054. Mo– and W–cyclopentadienone com-
plexes: (b) Slugovc, C.; Mauthner, K.; Mereiter, K.;
Schmid, R.; Kirchner, K. Organometallics 1996, 15, 2954.
Os–cyclopentadienone complexes: (c) Washington, J.;
McDonald, R.; Takats, J.; Menashe, N.; Reshef, D.;
Shvo, Y. Organometallics 1995, 14, 3996. Ni–cyclopenta-
dienone complexes: (d) Tamao, K.; Kobayashi, K.; Ito,
Y. Synlett 1992, 539.
Acknowledgements
We are grateful to the National Institutes of Health,
General Medical Sciences (GM56677) and Gencorp for
support of this work.
References
5. Pearson has carried out stereoselective additions to
ketones pendant to iron cyclopentadienone complexes.
See Ref. 3c.
1. Ogliaruso, M. A.; Romanelli, M. G.; Becker, E. I. Chem.
Rev. 1965, 65, 261.

6990
J. E. Imbriglio, J. D. Rainier / Tetrahedron Letters 42 (2001) 6987–6990
6. (a) Rainier, J. D.; Imbriglio, J. E. J. Org. Chem. 2000, 65,
12: Viscous oil; 1H NMR (500 MHz, C6D6) l 7.68 (d,
J=8.0 Hz, 1H), 6.99 (d, J=8.5 Hz, 1H), 6.93 (t, J=7.5 Hz,
7272; (b) Rainier, J. D.; Imbriglio, J. E. Org. Lett. 1999,
1, 2037.
1H), 6.87 (t, J=7.5 Hz, 1H), 0.54 (s, 9H), 0.49 (s, 9H); 13
C
7. Moyano, A.; Charbonnier, F.; Greene, A. E. J. Org. Chem.
NMR (125 MHz, C6D6) l 208.4, 177.2, 161.3, 147.1, 128.9,
124.6, 123.9, 123.6 113.1, 93.9, 62.3, 61.7, 0.21, −0.78; IR
(CH2Cl2) 3056, 2978, 2303, 2062, 2009, 1620 (cm−1); MS
(FAB+) 455 (MH+), 398, 307, 289, 154 m/z; HRMS calcd
for C20H23O5Si2Fe (MH+) 455.0434, found 455.0440.
15: Pale yellow solid; mp 136–138°C; 1H NMR (500 MHz,
C6D6) l 3.18 (s, 2H), 2.21 (d, J=14.0 Hz, 1H), 1.99 (t,
J=13.5 Hz, 1H), 0.67 (s, 3H), 0.50 (s, 3H), 0.47 (s, 9H),
0.34 (s, 9H); 13C NMR (125 MHz, C6D6) l 209.4, 176.4,
145.2, 88.4, 76, 65.9, 64.9, 35.2, 29.2, 25.5, 23.8, −0.10,
−0.58; IR (CH2Cl2) 3048, 2978, 2061, 1992, 1975 cm−1; MS
(FAB+) 449 (MH+), 393, 392, 246, 185 m/z; HRMS calcd
for C29H29O5Si2Fe (MH+) 449.0903, found 449.0904.
1987, 52, 2919.
8. Because of their instability to chromatographic purifica-
tion, ynol ethers 2, 5, and 8 were used in the subsequent
cycloaddition chemistry without purification.
9. In comparison, the tosyl protected ynamines correspond-
ing to 2, 5, and 8 underwent [2+2+1] cycloaddition to give
cyclopentadienone–iron complexes in 84, 96, and 54%
yields, respectively.
10. As has been discussed by others, unsubstituted acyclic
ethers adopt a ground state conformation that orients the
alkyl substituents anti to one another, see: (a) Eliel, E. L.;
Wilen, S. H.; Mander, L. N. Stereochemistry of Organic
Compounds; Wiley: New York, 1994; p. 611; (b) Visser, M.
S.; Heron, N. M.; Didiuk, M. T.; Sagal, J. F.; Hoveyda,
A. H. J. Am. Chem. Soc. 1996, 118, 4291; (c) Crimmins,
M. T.; Choy, A. L. J. Am. Chem. Soc. 1999, 121, 5653.
11. Simonian, S. O.; Smit, W. A.; Gybin, A. S.; Shashkov, A.
S.; Mikaelian, G. S.; Tarasov, V. A.; Ibragimov, I. I.;
Caple, R.; Froen, D. E. Tetrahedron Lett. 1986, 27, 1245.
12. We saw little to no enhancement in yield when alumina was
included in the reaction for the other ynol ether substrates.
13. The regiochemistry of 18 was determined through NOE
experiments. The assignments for 19–22 were based upon
these experiments.
1
19: H NMR (500 MHz, C6D6) l 8.28 (s, 1H), 8.12 (d,
J=8.5 Hz, 1H), 7.35 (d, J=8.0 Hz, 1H), 7.11 (m, 2H), 4.18
(q, J=7.0 Hz, 2H), 1.08 (t, J=7.0 Hz, 3H), 0.74 (s, 9H),
0.42 (s, 9H); 13C NMR (125 MHz, C6D6) l 169.4, 161.3,
157.3, 136.4, 135.3, 133.4, 130.6, 125.6, 125.1, 124.3, 123.7,
122.6, 121.2, 61.2, 14.3, 1.85, −0.97; IR (CH2Cl2) 3048,
2987, 2295, 1706, 1455 (cm−1); MS (FAB+) 385 (MH+), 369,
307, 289, 154 m/z; HRMS calcd for C21H29O3Si2 (MH+)
385.1655, found 385.1641.
1
21: H NMR (500 MHz, C6D6) l 7.99 (s, 1H), 4.14 (q,
J=7.0 Hz, 2H), 3.37 (s, 2H), 2.52 (s, 2H), 1.05 (t, J=7.0
Hz, 3H), 0.68 (s, 6H), 0.50 (s, 9H), 0.39 (s, 9H);13C NMR
(125 MHz, C6D6) l 170.5, 160.0, 143.6, 137.9, 127.3, 126.9,
74.9, 60.9, 42.3, 28.5, 24.7, 14.3, 2.9, −1.1; IR (CH2Cl2)
3048, 2978, 2303, 1715, 1412 (cm−1); MS (FAB+) 379
(MH+), 363, 307, 289, 154 m/z; HRMS calcd for
C20H35O3Si2 (MH+) 379.2125, found 379.2129.
14. Herndon was unable to trap a 1,2-diphenyl-4-oxocyclopen-
tadienone either intramolecularly with an unactivated
alkene or intermolecularly with DMAD. See: Herndon, J.
W.; Patel, P. P. Tetrahedron Lett. 1997, 38, 59.
1
15. All new compounds were characterized by H, 13C NMR,
IR and HRMS. Selected examples: