Synthesis and Chemoselective Reactivity of 3-aminocyclopentadienones

Article abstract of DOI:10.1021/ol9912128

(Matrix Presented) This Letter describes the synthesis and chemoselective cycloaddition chemistry of 3-aminocyclopentadienones.

Full text of DOI:10.1021/ol9912128

ORGANIC
LETTERS
1999
Vol. 1, No. 12
2037-2039
Synthesis and Chemoselective
Reactivity of
3-Aminocyclopentadienones
Jon D. Rainier* and Jason E. Imbriglio
Department of Chemistry, The UniVersity of Arizona, Tucson, Arizona 85721
rainier@u.arizona.edu
Received November 2, 1999
ABSTRACT
This Letter describes the synthesis and chemoselective cycloaddition chemistry of 3-aminocyclopentadienones.
Cyclopentadienones have been widely recognized as having
a high degree of synthetic potential.1-3 Unfortunately, their
propensity to dimerize1,2 has limited their use in synthesis
to masked cyclopentadienones3 or to those containing
multiple aromatic rings.4 As part of our program targeting
the use of cyclopentadienones in the synthesis of complex
molecules, we became interested in 3-aminocyclopentadi-
enones5 since the divergent electronic properties present in
the two enone double bonds would provide us with the
opportunity to carry out chemoselective manipulations.
Outlined herein are our preliminary results that not only
describe the synthesis of 3-aminocyclopentadienones but also
their unique properties in cycloaddition chemistry.
We envisioned 3-aminocyclopentadienones as arising from
cobalt-mediated [2 + 2 + 1] cycloaddition reactions between
nitrogen acetylenes (ynamines) and alkynes.6,7 We were
hopeful that any dimerization problems could be avoided
through the judicious choice of the nitrogen protecting group
as well as through trimethylsilyl substitution on the cyclo-
pentadienone.8
We initially targeted aminocyclopentadienone complex 4
from a cobalt-induced intramolecular cycloaddition reaction
(Scheme 1).9 The requisite yne-ynamine cyclization precur-
Scheme 1 Generation of Aminocyclopentadienone Complex 4
(1) For a discussion of the properties and reactivity of cyclopentadienones,
see: Ogliaruso, M. A.; Romanelli, M. G.; Becker, E. I. Chem. ReV. 1965,
65, 261.
(2) For a recent example of the dimerization of a non-aryl-substituted
cyclopentadienone, see: West, F. G.; Gunawardena, G. U. J. Org. Chem.
1993, 58, 5043.
(3) (a) For oxime-protected cyclopentadienones, see: Mackay, D.;
Papadopoulos, D.; Taylor, N. J. J. Chem. Soc., Chem. Commun. 1992, 325.
(b) For cyclopentadiene-protected cyclopentadienones, see: Dols, P. P. M.
A.; Klunder, A. J. H.; Zwanenburg, B. Tetrahedron 1994, 50, 8515 and
references therein. (c) For a review discussing cyclopentadienones masked
as 4-acetoxycyclopentenones, see: Harre, M. Raddatz, P.; Walenta, R.;
Winterfeldt, E. Angew. Chem., Int. Ed. Engl. 1982, 21, 480.
(4) See ref 1 and (a) Yamashita, Y.; Miyauchi, Y.; Masumura, M. Chem.
Lett. 1983, 489. (b) Yamashita, Y.; Masumura, M. Tetrahedron Lett. 1979,
1765.
sor 3 was synthesized in two steps from tosylaziridine (1).
Namely, ring opening of 1 with trimethysilylacetylide
(5) For an example of a tetraamine-substituted cyclopentadienone, see:
Lepage, T.; Nakasuji, K.; Breslow, R. Tetrahedron Lett. 1985, 26, 5919.
10.1021/ol9912128 CCC: $18.00 © 1999 American Chemical Society
Published on Web 11/17/1999

followed by ynamine formation using Stang’s protocol gave
yne-ynamine 3 in synthetically useful yields.7,10 To our
delight, when 3 was subjected to CpCo(CO)2 and photolysis
at low temperature we were able to isolate complexed
cyclopentadienone 4 in 57% yield (Scheme 1).
ketones.15,16 We were gratified to isolate adduct 8 in 82%
yield when cyclopentadienone 5 was condensed with acrolein
(eq 1). This experiment represents one of the very few
examples of the chemoselective functionalization of a non-
aryl-substituted cyclopentadienone.1,17
With ready access to 4, we set out to explore its reactivity.
Oxidative decomplexation with ceric ammonium nitrate
(CAN)9 at 0 °C provided a bright yellow solution of 5 after
aqueous workup. Interestingly, CAN had not only decom-
plexed the cobalt but it had also chemoselectively protode-
silylated the vinylogous amide.11
Although 5 was reasonably stable in solution, it decom-
posed upon concentration.12 For this reason 5 was character-
ized via its reactivity with dienophiles.13 Exposure of a
solution of 5, CH3CN, and benzene to dimethyl acetylene-
dicarboxylate (DMAD) at 80 °C for 12 h resulted in the
formation of indolene 7 in 78% yield (from cobalt complex
4). Likewise, addition of methyl acrylate to 5 resulted in
diene 6 in 67% yield after decarbonylation.
The structure of 8 was determined both spectroscopically
as well as through X-ray crystallography (Figure 1).
While pleased with our ability to use 5 as the 4π
component in cycloadditions,14 the experiments outlined in
Scheme 2 do not demonstrate the chemoselectivity of interest
Scheme 2. 3-Aminocyclopentadienone 5 in Diels-Alder
Reactions with Dienophiles
Figure 1. X-ray crystal structure of 8.
The reaction appears to be general as 5 also reacted with
methyl vinyl ketone, crotonaldehyde, and methacrolein to
give adducts 9, 10, and 11, respectively (Table 1).
Table 1. Hetero Diels-Alder Cycloaddition of 5
to us. With this in mind, we turned to the use of 5 in hetero-
Diels-Alder cycloadditions with unsaturated aldehydes and
(6) For reviews discussing the chemistry of ynamines, see: (a) Ficini, J.
Tetrahedron 1976, 32, 1449. (b) Himbert, G. Methoden der Organischen
Chemie (Houben-Weyl); Kropf, H., Schaumann, E., Eds.; Georg Thieme
Verlag: Stuttgart, 1993; p 3267.
(7) For recent ynamine cycloaddition reactions, see: (a) Witulski, B.;
Stengel, T. Angew. Chem., Int. Ed. 1998, 37, 489. (b) Witulski, B.; Stengel,
T. Angew. Chem., Int. Ed. 1999, 38, 2426. (c) Witulski, B.; Stengel, T. J.
Chem. Soc., Chem. Commun. 1999, 1879. (d) Hsung, R. P.; Zificsak, C.
A.; Wei, L.-L.; Douglas, C. J.; Xiong, H.; Mulder, J. A. Org. Lett. 1999, 1,
1237.
Having successfully demonstrated the enhanced reactivity
of the vinylogous amide with unsaturated aldehydes and
(8) Both 2,3,5- and 2,3,4-tris(trimethylsilyl)cyclopentadienones are rea-
sonably stable at room temperature. See: Maier, G.; Lage, H. W.;
Reisenauer, H. P. Angew. Chem., Int. Ed. Engl. 1981, 20, 976.
(9) Vollhardt has synthesized the corresponding all-carbon cyclopenta-
dienone. See: Gesing, E. R. F.; Tane, J. P.; Vollhardt, K. P. C. Angew.
Chem., Int. Ed. Engl. 1980, 19, 1023.
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Org. Lett., Vol. 1, No. 12, 1999

ketones, we set out to selectively functionalize the isolated
enone in the presence of the vinylogous amide. Once again
we were interested in taking advantage of the divergent
properties of the two alkenes in 5 and examined the reaction
of 5 with cyclopentadiene.16b To our delight, enone adduct
12 was isolated in 57% yield when 5 was exposed to
cyclopentadiene (eq 2).
have demonstrated that 5 can serve as both the 4π and 2π
component in cycloaddition reactions. We are currently
focused on the optimization of the reactions that have been
discovered, the use of other 3-aminocyclopentadienones in
cycloaddition chemistry, and the use of the substrates from
these reactions in the synthesis of interesting targets.
Acknowledgment. We gratefully acknowledge the Ameri-
can Cancer Society (IRG-110T) and the University of
Arizona for support of this work. We would like to thank
Professor James W. Herndon (New Mexico State University)
for helpful discussions. We would also like to thank Mr.
Jeff Bilsky for bringing forward quantities of 3. We are
grateful to Dr. Arpad Somogyi for help with mass spectra
analysis, Dr. Neil Jacobsen and Mr. Shawn P. Allwein for
help with NMR experiments, and Dr. Mike Carducci for
obtaining the X-ray crystal structure of 8.
To conclude, 3-aminocyclopentadienone 5 can be ef-
ficiently synthesized from a cobalt mediated yne-ynamine
cycloaddition reaction. By varying its coupling partner, we
Supporting Information Available: Experimental pro-
cedures and spectroscopic data for compounds 4 and 6-12.
This material is free of charge via the Internet at http://
pubs.acs.org.
(10) Modern Acetylene Chemistry; Stang, P. J., Diederich, F., Eds;
VCH: Weinheim, 1995.
(11) The position of the remaining trimethylsilyl group in 5 was initially
determined spectroscopically (NOE experiments) on indolene 7. A subse-
quent X-ray structure of 8 confirmed this assignment.
(12) Cyclopentadienone 5 was stable at 80 °C for up to 24 h in a 1:1
acetonitrile-benzene solution but decomposed to unrecognizable products
upon concentration.
(13) For the use of cyclopentadienones as dienes in Diels-Alder
cycloadditions, see ref 1 and Baraldi, P. G.; Barco, A.; Benetti, S.; Pollini,
G. P.; Polo, E.; Simoni, D. J. Chem. Soc., Chem. Commun. 1984, 1049.
(14) A similar vinylogous ester was unreactive in analogous cycloaddition
reactions. See: Herndon, J. W.; Patel, P. P. Tetrahedron Lett. 1997, 38,
59.
OL9912128
(15) For an example of the use of an enamine in a hetero-Diels-Alder
cycloaddition reaction, see: Stork, G.; Landesman, H. K. J. Am. Chem.
Soc. 1956, 78, 5129.
(16) For the use of cyclopentadienones as 2π components in cycloaddition
chemistry, see ref 1 and (a) Gavina, F.; Costero, A. M.; Gil, P.; Palazon,
B.; Luis, S. V. J. Am. Chem. Soc. 1981, 103, 1797. (b) Depuy, C. H.; Isaks,
M.; Eilers, K. L.; Morris, G. F. J. Org. Chem. 1964, 29, 3503.
(17) Herndon has been able to carry out the in situ protonation of the
corresponding reduced vinylogous esters, see: Herndon, J. W.; Zhu, J. Org.
Lett. 1999, 1, 15 and references contained therein.
Org. Lett., Vol. 1, No. 12, 1999
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