Zheng et al.
CHART 1. 9,10-Dioxabimanes (Bimanes)
SCHEME 1. Synthesis of Complexes 3-5
novel Fischer carbene complexes or formation of novel organic
products.6
1
,5-Diazabicyclo[3.3.0]octadienediones (briefly, 9,10-diox-
abimanes or “bimanes”) are a class of bicyclic N-heterocyclic
compounds, as described in Chart 1. The syn compounds are
usually strongly fluorescent, but the anti isomers are normally
leading the mixed bimane products to be prepared in rather low
yields, and isolation/purification of the desired products to be
7
nonfluoroscent and possibly phosphorescent. Bimane deriva-
tives are important labeling agents and have been successfully
7
c
handled with much difficulty. We recently found that NH-
containing pyrazoles and CdN-containing substituted oxazolines
react with 1-alkynyl Fischer carbene complexes (OC)5Md
C(OEt)CtCPh (1) (M ) Cr, W) to afford Michael addition
and consecutive cycloaddition/cyclization products, respectively.6
Encouraged by these results, the multiple tautomerism of
substituted pyrazolinones, and the multiple reactivities of
8
used as fluorescent probes for protein structural analysis. A
four-step synthesis starting from alkylation of a â-ketoester, and
then via pyrazolinone, chloropyrazolinone, and dechlorination
affords symmetrical bimanes, i.e., the syn-bimane (A) and its
anti isomer (B) (Chart 1). However, symmetrical bimanes are
usually prepared in low to moderate yields, strongly depending
on the properties of the employed â-ketoesters and reaction
a,b
1
-alkynyl Fischer carbene complexes (1), we investigated the
7
conditions. Thus, seven steps are necessary for synthesis of
reactions of 1 and substituted pyrazolinones (2) and oxidative
demetalation of the newly formed carbene complexes. Herein,
we report our findings in this area, which constitutes a new
method to synthesize mixed bimanes and construct novel
N-heterocyclic ring systems.
mixed (unsymmetrical) bimanes. That is, two different chloro-
pyrazolinones are reacted to give mixed bimanes of types C
and D as well as up to five other possible bimane products,
(3) For selected recent reviews, see: (a) Barluenga, J.; Fern a´ ndez-
Rodr ´ı guez, M. A.; Aguilar, E. J. Organomet. Chem. 2005, 690, 539. (b)
Barluenga, J.; Santamaria, J.; Tom a´ s, M. Chem. ReV. 2004, 104, 2259. (c)
Herndon, J. W. Coord. Chem. ReV. 2003, 243, 3. (d) Sierra, M. A. Chem.
ReV. 2000, 100, 3591. (e) D o¨ tz, K. H.; J a¨ kel, C.; Haase, W. C. J. Organomet.
Chem. 2001, 617/618, 119. (f) Barluenga, J.; Flor e´ z, J.; Fa n˜ an a´ s, F. J. J.
Organomet. Chem. 2001, 624, 5. (g) de Meijere, A.; Schirmer, H.; Duetsch,
M. Angew. Chem., Int. Ed. 2000, 39, 3964. (h) Herndon, J. W. Tetrahedron
Results and Discussion
Reactions of 1 with Alkyl-Substituted Pyrazolinones (2a-
e). The reactions of 1-alkynyl Fischer carbene complexes
(OC)5MdC(OEt)CtCPh (M ) Cr (1a), W (1b)) with substi-
tuted pyrazolinones, i.e., 3-methyl-2-pyrazolin-5-one (2a), 3-n-
propyl-2-pyrazolin-5-one (2b), 3,4-dimethyl-2-pyrazolin-5-one
(2c), 3,4-trimethylene-2- pyrazolin-5-one (2d), and 3,4-tetram-
ethylene-2-pyrazolin-5-one (2e), were carried out in THF at 50
2
000, 56, 1257. (i) Barluenga, J.; Fa n˜ an a´ s, F. J. Tetrahedron 2000, 56,
4
597. (j) Aumann, R. Eur. J. Org. Chem. 2000, 17.
(4) (a) Capriati, V.; Florio, S.; Luisi, R.; Perna, F. M.; Barluenga, J. J.
Org. Chem. 2005, 70, 5852. (b) Florio, S.; Perna, F. M.; Luisi, R.; Barluenga,
J.; Rodr ´ı guez, F.; Fa n˜ an a´ s, F. J. J. Org. Chem. 2004, 69, 5480.
(
5) (a) Hegedus, L. S. Tetrahedron 1997, 53, 4105. (b) Hegedus, L. S.
Top. Organomet. Chem. 2004, 13, 157.
6) For selected recent references on reactions of Fischer carbene
°
C or in dioxane at 65 °C. Diethyl ether, acetonitrile, toluene,
(
hexane, pentane, dichloromethane, and chloroform were tested
as the reaction media, but only THF and dioxane were found
to be the suitable reaction solvents in which N-heterocyclic
Fischer carbene complexes were formed in decent yields. The
reaction rates varied so much that the starting complexes were
completely consumed within 15-60 min by TLC monitoring
on silica gel. Three types of new N-heterocyclic Fischer carbene
complexes with different polarities and colors, i.e., complexes
of types 3, 4, and 5, were isolated as the products (Scheme 1).
The carbene complex products of tungsten were usually obtained
in yields higher than those of their chromium analogues (Table
1). Complexes 3a-j (5.5-21.5%) were formed as the minor
products, and 4a-j (15.1-43.7%) and their anti isomers 5a-j
complexes with NH/CdN bond-containing compounds, see: (a) Gu, K.
C.; Chen, J. Z.; Zheng, Z. Y.; Wu, S. Z.; Wu, X. W.; Han, X. W.; Yu, Z.
K. Polyhedron 2005, 24, 173, and references therein. (b) Chen, J. Z.; Yu,
Z. K.; Zheng, Z. Y.; Gu, K. C.; Wu, S. Z.; Zeng, F. L.; Tan, W. Q.; Wu,
X. W.; Xiao, W.-J. Organometallics 2005, 24, 302. (c) Llordes, A.; Sierra,
M. A.; Lopez-Alberca, M. P.; Molins, E.; Ricart, S. J. Organomet. Chem.
2
005, 690, 6096. (d) Barluenga, J.; Su a´ rez-Sobrino, A. L.; Tom a´ s, M.;
Garc ´ı a-Granda, S.; Santiago-Garc ´ı a, R. J. Am. Chem. Soc. 2001, 123, 10494.
e) Barluenga, J.; Tom a´ s, M.; Rubio, E.; L o´ pez-Pelegr ´ı n, J. A.; Garc ´ı a-
(
Granda, S.; Priede, M. P. J. Am. Chem. Soc. 1999, 121, 3065. (f) Aumann,
R.; Jasper, B.; Fr o¨ hlich, R. Organometallics 1995, 14, 2447.
(7) For selected leading references on preparation and properties of
bimanes, see: (a) Kosower, E. M.; Pazhenchevsky, B.; Hershkowitz, E. J.
Am. Chem. Soc. 1978, 100, 6516. (b) Kosower, E. M.; Bernstein, J.;
Goldberg, I.; Pazhenchevsky, B.; Goldstein, E. J. Am. Chem. Soc. 1979,
1
1
01, 1620. (c) Kosower, E. M.; Pazhenchevsky, B. J. Am. Chem. Soc. 1980,
02, 4983. (d) Kosower, E. M.; Pazhenchevsky, B.; Dodiuk, H.; Kanety,
(2.4-53.0%) were isolated as the major products. It is note-
H.; Faust, D. J. Org. Chem. 1981, 46, 1666. (e) Kosower, E. M.; Zbaida,
D.; Baud’huin, M.; Marciano, D.; Goldberg, I. J. Am. Chem. Soc. 1990,
worthy that complexes 5g,h were not isolated in measurable
yields in the cases of using the pyrazolinone 2d (entries 9 and
1
12, 7305. (f) Shalev, D. E.; Chiacchiera, S. M.; Radkowsky, A. E.;
1
0, Table 1). Yields of complexes 4e,f and 5e,f were obviously
Kosower, E. M. J. Org. Chem. 1996, 61, 1689. (g) Kosower, E. M.; Ben-
Shoshan, M. J. Org. Chem. 1996, 61, 5871.
improved when the reactions were carried out in dioxane at 65
°C in the cases of using 2c (entries 5-8, Table 1). For example,
the reaction of 1a with 2c in THF at 50 °C afforded 3e, 4e, and
(8) For selected recent references, see: (a) Sosa-Peinado, A.; Gonzalez-
Andrade, M. Biochemistry 2005, 44, 15083. (b) Mansoor, S. E.; Farrens,
D. L. Biochemistry 2004, 43, 9426. (c) Lee, S.; Rosazza, J. P. N. Org. Lett.
5
e in 5.5%, 15.1%, and 2.4% yields, respectively, and the
2
1
004, 6, 365. (d) Radkowsky, A. E.; Kosower, E. M. J. Am. Chem. Soc.
986, 108, 4527.
reaction in dioxane at 65 °C gave the same products in 7.4%,
9696 J. Org. Chem., Vol. 71, No. 26, 2006