Rhodium-catalyzed intramolecular alkyne-carbodiimide Pauson-Khand-type reaction

Article abstract of DOI:10.1021/ol063123i

Figure presented An efficient, Rh-catalyzed intramolecular Pauson-Khand-type carbonylation of alkyne-carbodiimides leading to 4,5-dihydro-1H-pyrrolo[2,3-b]pyrrolin-2-ones and 1H-pyrrolo[2,3-b]indol-2-ones is described.

Full text of DOI:10.1021/ol063123i

ORGANIC
LETTERS
2007
Vol. 9, No. 7
1239-1241
Rhodium-Catalyzed Intramolecular
Alkyne-carbodiimide
Pauson−Khand-Type Reaction
Takao Saito,* Katsuya Sugizaki, Takashi Otani, and Toshiyuki Suyama
Department of Chemistry, Faculty of Science, Tokyo UniVersity of Science,
Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
tsaito@rs.kagu.tus.ac.jp
Received December 26, 2006
ABSTRACT
An efficient, Rh-catalyzed intramolecular Pauson−Khand-type carbonylation of alkyne-carbodiimides leading to 4,5-dihydro-1H-pyrrolo[2,3-
b]pyrrolin-2-ones and 1H-pyrrolo[2,3-b]indol-2-ones is described.
As part of our ongoing interest in designing new synthetic
strategies for nitrogen heterocycles, we have developed facile
and efficient methods involving ring-forming reactions such
as electrocyclizations, intramolecular hetero Diels-Alder
reactions, hetero Michael additions, etc., of functionalized
carbodiimides and ketenimines as the key synthetic step.1 It
is well documented that [2+2+1]-cocyclization of an alkyne,
an alkene, and carbon monoxide promoted by transition
metals, which is known as the Pauson-Khand reaction (when
Co2(CO)8 is used) or the Pauson-Khand-type reaction (when
other metal complexes are used), is a powerful and elegant
synthetic method for cyclopentenones and their derivatives.2
The hetero Pauson-Khand reaction has also been developed
in which a carbonyl or imine functionality instead of an
alkene or alkyne π-component is incorporated as a hetero-
alkene counterpart.3 Allenes are versatile building blocks in
organic synthesis,4 and recently, the synthetic utility of such
cyclocarbonylation reactions has been greatly enhanced
through the use of an allene functionality instead of alkenes.5
However, there had been no reports on Pauson-Khand-type
(2) For reviews on the Pauson-Khand reaction: (a) Gibson, S. E.;
Stevenazzi, A. Angew. Chem., Int. Ed. 2003, 42, 1800. (catalytic) (b) Blanco-
Urgoiti, J.; Anorbe, L.; Perez-Serrano, L.; Dominguez, G.; Perez-Castells,
J. Chem. Soc. ReV. 2004, 33, 32. (c) Rivero, M. R.; Adrio, J.; Carretero, J.
C. Eur. J. Chem. 2002, 2881. (d) Sugihara, T.; Yamaguchi, M.; Nishizawa,
M. Chem.-Eur. J. 2001, 7, 1589. (e) Brummond, K. M.; Kent, J. L.
Tetrahedron 2000, 56, 3263. (f) Jeong, N. In Transition Metals in Organic
Synthesis; Beller, M., Bolm, C., Eds; Wiley-VCH: Weinheim, 1998; Vol.
1, pp 560-577. (g) Schore, N. E. Org. React. 1991, 40, 1. (h) Geis, O.;
Schmalz, H.-G. Angew. Chem., Int. Ed. 1998, 37, 911. (i) Fru¨hauf, H.-W.
Chem. ReV. 1997, 97, 523. (j) Fletcher, A. J.; Christie, S. D. R. J. Chem.
Soc., Perkin Trans. 1 2000, 1657. (k) Hanson, B. E. Comments Inorg. Chem.
2002, 23, 289.
(3) For carbonyl Pauson-Khand, see: (a) Kablaouli, N. M.; Buchwald,
S. L. J. Am. Chem. Soc. 1996, 118, 3182. (b) Kablaouli, N. M.; Hick, F.
A.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118, 5818. (c) Cowe, W. E.;
Vu, A. T. J. Am. Chem. Soc. 1996, 118, 1557. (d) Mandal, S. K.; Amin, S.
R.; Crowe, W. E. J. Am. Chem. Soc. 2001, 123, 6457. (e) Yu, C.-M.; Hong,
Y.-T.; Lee, J.-H. J. Org. Chem. 2004, 69,8506. (f) Chatani, N.; Morimoto,
T.; Fukumoto, Y.; Murai, S. J. Am. Chem. Soc. 1998, 120, 5335. (g) Fuji,
K.; Morimoto, T.; Tsutsumi, K.; Kakiuchi, K. Chem. Commun. 2005, 3295.
(h) Kang, S.-K.; Kim, K.-J.; Hong, Y.-T. Angew. Chem. 2002, 114, 1654.
For imine Pauson-Khand, see: (i) Imhof, W.; Anders, E.; Go¨bel, A.; Go¨rls,
H. Chem.-Eur. J. 2003, 9, 1166. (j) Go¨bel, A.; Imhof, W. Chem. Commun.
2001, 593.
(1) (a) Saito, T.; Ohkubo, T.; Kuboki, H.; Maeda, M.; Tsuda, K.;
Karakasa, T.; Satsumabayashi, S. J. Chem. Soc., Perkin Trans. 1 1998, 3065.
(b) Saito, T.; Tsuda, K. Tetrahedron Lett. 1996, 37, 9071. (c) Saito, T.;
Tsuda, K.; Saito, Y. Tetrahedron Lett. 1996, 37, 209. (d) Saito, T.; Ohmori,
H.; Ohkubo, T.; Motoki, S. Chem. Commun. 1993, 1802. (e) Saito, T.;
Ohkubo, T.; Maruyama, K.; Kuboki, H.; Motoki, S. Chem. Lett. 1993, 1127.
(f) Saito, T.; Ohmori, H.; Furuno, E.; Motoki, S. Chem. Commun. 1992,
22. (g) Saito, T.; Nakane, M.; Miyazaki, T.; Motoki, S. J. Chem. Soc., Perkin
Trans. 1 1989, 2140. (h) Saito, T.; Nakane, M.; Endo, M.; Yamashita, H.;
Oyamada, Y.; Motoki, S. Chem. Lett. 1986, 135.
(4) (a) Zimmer, R.; Dinesh, C. U.; Nandanan, E.; Khan, F. A. Chem.
ReV. 2000, 100, 3067. (b) The Chemistry of Ketenes, Allenes, and Related
Compounds; Patai, S., Ed.; John Wiley & Sons: New York, 1980; Part 1
& 2. (c) Modern Allene Chemistry; Krause, N., Hashmi, A. S. K., Eds.;
Wiley-VCH: Weinheim, 2004. (d) Bates, R. W.; Satcharoen, V. Chem.
Soc. ReV. 2002, 31, 12.
10.1021/ol063123i CCC: $37.00
© 2007 American Chemical Society
Published on Web 03/10/2007

reactions involving heterocumulene as a 2π-component,6
until our recent report of the heterocumulenic Pauson-
Khand-type reaction appeared.7 The reaction involved alkyne-
carbodiimides as both 2π-components in the intramolecular
[2+2+1]-cyclocarbonylation. Unfortunately, however, it
required stoichiometric amounts of Mo(CO)6 in the presence
of DMSO as a promoter upon heating in toluene to obtain
good to fair yields of the Pauson-Khand products, pyrrolo-
[2,3-b]pyrrolinones and pyrrolo[2,3-b]indolones.7 Our atten-
tion has now focused on the development of a catalytic
version of the heterocumulenic Pauson-Khand-type reaction.
Here, we present the rhodium-catalyzed heterocumulenic
Pauson-Khand-type reaction of alkyne-carbodiimides for the
first time.8
First, screening of metal catalysts2 in combination with
an additive (ligand) was performed in the Pauson-Khand-
type reaction of N-[(o-phenylethynyl)]phenyl-N′-propyl-
carbodiimide (1a) under an atmospheric pressure of carbon
monoxide in toluene at ca. 120 °C. Selected results are listed
in Table 1. The use of a stoichiometric amount of Mo(CO)6
(100 mol %)3d,7 in the presence of 5 equiv of DMSO afforded
Pauson-Khand product 2a in 55% yield (entry 1). However,
catalytic use (5 mol %) of the same Mo complex and DMSO
(25 mol %) under the same conditions required a longer
reaction time (8 h) and was less effective, as it gave 16%
Table 1. Screening of Catalysts and Additives in
Pauson-Khand-Type Reactions of 1a to Give 2a
time yield
entry
catalyst
(mol %) additive (mol %) (h)
(%)a
1
2
3
4
5
6b
7b
8c
9c
10c
11c
12c
Mo(CO)6
Mo(CO)6
Cr(CO)6
W(CO)6
Ru3(CO)12
Co2(CO)8
Co2(CO)8
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
(100)
(5)
(5)
(5)
(5)
(5)
(5)
(5)
(5)
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
P(OPh)3
PPh3
(500)
(25)
(25)
(25)
(25)
(25)
(20)
(22)
(11)
(11)
(5.5)
(11)
1
8
7
55
16
0
13
7
0
0
8
10
7
12
28
6
dpped
6
1.5
2
4
17
77
58
29
(5)
(2.5)
(5)
dpppe
dpppe
dppbf
a
Yield of isolated product 2a. b Dimethoxyethane was used as solvent.
c
d
e
cod ) 1,5-cyclooctadiene. 1,2-Bis(diphenylphosphino)ethane. 1,3-
Bis(diphenylphosphino)propane. 1,4-Bis(diphenylphosphino)butane.
f
(5) For a review on allenic Pauson-Khand reactions, see: Alcaide, B.;
Almendros, P. Eur. J. Org. Chem. 2004, 3377. For selected recent reports
on allenic Pauson-Khand reactions, see (allene-ene): (a) Wender, P. A.;
Croatt, M. P.; Deschamps, N. M. Angew. Chem., Int. Ed. 2006, 45, 2459.
(allene-yne): (b) Mukai, C.; Hirose, T.; Teramoto, S.; Kitagaki, S.
Tetrahedron 2005, 61, 10983. (c) Mukai, C.; Inagaki, F.; Yoshida, T.;
Yoshitani, K.; Hara, Y.; Kitagaki, S. J. Org. Chem. 2005, 70, 7159. (d)
Mukai, C.; Inagaki, F.; Yoshida, T.; Kitagaki, S. Tetrahedron Lett. 2004,
45, 4117. (e) Shibata, T.; Kadowaki, S.; Hirase M.; Takagi, K. Synlett 2003,
573. (f) Narasaka, K.; Shibata, T. Chem. Lett. 1994, 315. (allenic, first
report): (g) Shibata, T.; Koga, Y.; Narasaka, K. Bull. Chem. Soc. Jpn. 1994,
68, 911. (h) Brummond, K. M.; Chen, H.; Fisher, K. D.; Kerekes, A. D.;
Rickards, B.; Still, P. C.; Geib, S. J. Org. Lett. 2002, 4, 1931. (i) Brummond,
K. M.; Kerekes, A. D.; Wan, H. J. Org. Chem. 2002, 67, 5156. (j) Anorbe,
L.; Poblador, A.; Dominguez, G.; Perez-Castells, J. Tetrahedron Lett. 2004,
45, 4441. (k) Alcaide, B.; Almendros, P.; Allagoncillo, C. Chem.-Eur. J.
2002, 8, 1719. (l) Cao, H.; Flippen-Anderson, J.; Cook, J. M. J. Am. Chem.
Soc. 2003, 125, 3230. (m) Pagenkopf, B. L.; Belanger, D. B.; O’Mahony,
D. J. R.; Livinghouse, T. Synthesis 2000, 1009. (inter allene-yne): (n)
Antras, F.; Ahmar, M.; Cazes, B. Tetrahedron Lett. 2001, 42, 8153. (o)
Antras, F.; Ahmar, M.; Cazes, B. Tetrahedron Lett. 2001, 42, 8157. (allene-
carbonyl): (p) Yu, C.-M.; Hong, Y.-T. J. Org. Chem. 2004, 69, 8506.3e (q)
Kang, S.-K.; Kim, K.-J.; Hong, Y.-T. Angew. Chem. 2002, 114, 1654.3h
(6) To our knowledge, there are only three reports. (a) One is as early
as 1970 of the cocycloaddition reaction of diphenylcarbodiimide or phenyl
isocyanate, diphenylacetylene, and Fe(CO)5, which afforded indeed a
Pauson-Khand-type product in a reasonable yield: Ohshiro, Y.; Kinugasa,
K.; Minami, T.; Agawa, T. J. Org. Chem. 1970, 35, 2136. (b) Hoberg, H.;
Oster, B. W. J. Organomet. Chem. 1982, 234, C35. (c) Very recently, Ru-
catalyzed intermolecular Pauson-Khand-type cocyclization of isocyanates
has been reported. Kondo, T.; Nomura, M.; Ura, Y.; Wada, K.; Mitsudo,
T. J. Am. Chem. Soc. 2006, 128, 14816.
yield of 2a (entry 2). The reactions employing 5 mol % of
Cr(CO)6, W(CO)6, Ru3(CO)12,3e,g and Co2(CO)8 resulted in
much lower or no yield of 2a (entries 3-6), whereas
Co2(CO)8 (5 mol %) combined with P(OPh)3 (20 mol %)
provided 2a in somewhat better yield (entry 7). When
[RhCl(CO)dppp]2 (5 mol %) (generated in situ by mixing
[RhCl(cod)]2 and 1,3-bis(diphenylphosphino)propane (dppp,
11 mol %) as the ligand) was used,9 the best results were
obtained, with 77% yield of 2a (entry 10). The efficiency of
the catalytic system was found to be largely dependent on
the combination of the complex with its ligand. It is clear
that dppp is superior to the other phosphine ligands, P(OPh)3,
1,2-bis(diphenylphosphino)ethane (dppe), and 1,4-bis(di-
phenylphosphino)butane (dppb) for this substrate (entry 10
vs entries 8, 9, and 12).10 The amount of the catalyst,
[RhCl(CO)dppp]2, could be reduced to 2.5 mol %, while
maintaining a fairly good yield (58%) of 2a (entry 11).
Given the best result (entry 10, Table 1) in the model
reaction of 1a, we thus applied this catalytic system under
the optimized conditions to substrates 1 bearing a variety of
substituents (R1, R2) on the terminal alkyne and the nitrogen
atom. The results are shown in Table 2. The alkyl- and aryl-
substituted carbodiimides 1 produced moderate to good yields
of 2, whereas in the cases of carbodiimides 1b,g having a
substituent of R2 ) cyclohexyl, Pauson-Khand products
2b,g were obtained in lower yields. This is probably due to
(7) Saito, T.; Shiotani, M.; Otani, T.; Hasaba, S. Heterocycles 2003, 60,
1045. The catalytic version of this research was presented at: 85th Annual
Meeting of the Chemical Society of Japan, Yokohama, March, 2005;
Abstract 1B2-25. 35th Congress of Heterocyclic Chemistry, Osaka,
October, 2005; Abstract 2C-08. The International Chemical Congress of
Pacific Basin Societies, Honolulu, Hawaii, December, 2005; Abstract ORGN
1696.
(8) Very recently, Mukai et al. reported a synthesis of the indole alkaloid,
(()-physostigmine, through the first catalytic heterocumulenic Pauson-
Khand reaction of alkynylcarbodiimides for the construction of a pyrrolo-
[2,3-b]indol-2-one skeleton as the key step, where 10-20 mol % of
Co2(CO)8 and a tetramethylthiourea promoter (60-120 mol %) were
successfully applied. Mukai, C.; Yoshida, T.; Sorimachi, M.; Odani, A.
Org. Lett. 2006, 8, 83.
(9) (a) Jeong, N.; Lee, S.; Sung, B.-K. Organometallics 1998, 17, 3642.
(b) Jeong, N.; Seo, S. D.; Shin, J. Y. J. Am. Chem. Soc. 2000, 122, 10220.
(10) For a Pauson-Khand reaction using a Rh(I) complex catalyst, see:
Koga, Y.; Kobayashi, T.; Narasaka, K. Chem. Lett. 1998, 249. Mukai, C.;
Nomura, I.; Yamanishi, K.; Hanaoka, M. Org. Lett. 2002, 4, 1755. Refs
5b-d.
1240
Org. Lett., Vol. 9, No. 7, 2007

Table 2. Catalytic Pauson-Khand-Type Reaction of 1 to
Give 2a
Table 3. Catalytic Pauson-Khand-Type Reaction of 3 to
Give 4a
yield
time
(h)
yield
(%)b
R1
Ph
Ph
Ph
Ph
Ph
Me3Si
Me3Si
Me3Si
Me3Si
Me3Si
R2
n-Pr
c-Hex
Ph
p-MeC6H4
p-ClC6H4
n-Pr
c-Hex
Ph
2
entry
3
R1
R2
n-Pr
4
(%)b
entry
1
1
2
3
4
5
6
7
3a
3b
3c
3d
3e
3f
Me
Me
Me
Me
Et
4a
4b
4c
4d
4e
4f
0
43
44
47
46
46
47
1
2
3
4
5
1a
1b
1c
1d
1e
1f
1.5
1.5
1.5
1.5
1.5
2.0
2.5
1.5
1.5
1.5
2a
2b
2c
2d
2e
2f
2g
2h
2i
77
27
50
50
57
60
20
85
77
77
Ph
p-MeC6H4
p-ClC6H4
Ph
p-MeC6H4
p-ClC6H4
Et
Et
6
3g
4g
7
8
9
1g
1h
1i
3 (0.53 mmol), 0.15 M, at 120 °C of bath temp. b Yield of isolated 4.
a
p-MeC6H4
p-ClC6H4
10
1j
2j
In conclusion, the first examples of Rh-catalyzed Pauson-
Khand-type reactions of alkyne-carbodiimides are reported,
thus providing a facile and efficient route to the Pauson-
Khand products, pyrrolo-indolones and pyrrolo-pyrrolinones.
a
1 (0.23 mmol), 0.16 M, at 120 °C of bath temp. b Yield of isolated 2.
steric hindrance caused by the bulky cyclohexyl group in
the cyclization process.
Acknowledgment. Partial financial support by a Grant-
in-Aid for Scientific Research from the Ministry of Educa-
tion, Culture, Sport, Science and Technology, Japan, is
gratefully acknowledged.
To study the generality of the catalytic carbodiimide
Pauson-Khand reaction, this Rh catalyst was next applied
to the reaction of ethylene-tethered alkyne-carbodiimides 3
(Table 3). The use of 5 mol % of [RhCl(CO)dppp]2 catalyst
generated in situ also proved to be effective for the Pauson-
Khand-type reaction of N-(3-alkynyl)-N′-arylcarbodiimides
3b-g to furnish 4,5-dihydro-1H-pyrrolo[2,3-b]pyrrolin-2-
ones (4b-g) in acceptable yields, whereas the reaction of
N-(3-pentynyl)-N′-propylcarbodiimide 3a did not give any
cyclized products. The reason for the latter results can be
ascribed to the fact that dialkylcarbodiimides bearing less
bulky substituents (as in 3a) are apt to dimerize or deteriorate
under such harsh reaction conditions.11
Supporting Information Available: A typical experi-
mental procedure for synthesis of 2a and characterization
data of new compounds 1a,b, 1d-g, 1i,j, 2a-j, 3a-g, and
1
4b-g, and H NMR and 13C NMR spectra of compounds
1a,b, 1d-g, 1i,j, 2a-j, 3a-g, and 4b-g. This material is
available free of charge via the Internet at http://pubs.acs.org.
OL063123I
(11) Kurzer, F.; Douraghi-Zadeh, K. Chem. ReV. 1967, 67, 107.
Org. Lett., Vol. 9, No. 7, 2007
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