Synthesis and cyclometalation of a pyrido[3,2-e]-2,10b-diaza-cyclopenta[c]fluorene-1,3-dione scaffold

Article abstract of DOI:10.1016/j.tetlet.2006.10.054

The synthesis of a pyrido[3,2-e]-2,10b-diaza-cyclopenta[c]fluorene-1,3-dione scaffold is disclosed, which was synthesized using a Suzuki cross-coupling reaction and an intramolecular Heck cyclization as the key steps. This heterocyclic system can serve as

Full text of DOI:10.1016/j.tetlet.2006.10.054

Tetrahedron Letters 47 (2006) 8877–8880
Synthesis and cyclometalation of a pyrido[3,2-e]-2,10b-
diaza-cyclopenta[c]fluorene-1,3-dione scaffold
Seann P. Mulcahy, Patrick J. Carroll and Eric Meggers*
Department of Chemistry, University of Pennsylvania, 231 S. 34th St., Philadelphia, PA 19104, United States
Received 22 September 2006; accepted 10 October 2006
Abstract—The synthesis of a pyrido[3,2-e]-2,10b-diaza-cyclopenta[c]fluorene-1,3-dione scaffold is disclosed, which was synthesized
using a Suzuki cross-coupling reaction and an intramolecular Heck cyclization as the key steps. This heterocyclic system can serve as
a bidentate ligand as demonstrated by the formation and structural analysis of a derived ruthenium complex. The new scaffold
constitutes an interesting candidate for the development of organometallic protein kinase inhibitors.
ꢀ 2006 Elsevier Ltd. All rights reserved.
We recently started a research program that aims in
Bn
N
H
N
R
N
exploring the scope of using substitutionally inert metal
complexes to design bioactive small molecules.1,2 In our
concept we make use of the distinctive structural fea-
tures of transition metals and thus the main purpose
of the metal is to organize the organic ligands in the
three-dimensional space. Following this strategy, we dis-
closed over the last two years a series of simple ruthe-
nium-based protein kinase inhibitors such as 1, which
mimic the overall shape of the family of indolocarbazole
alkaloids (e.g., staurosporine, see Fig. 1).3 Almost all
our compounds include the pyridocarbazole ligand 2
as a key pharmacophore, which substitutes for the indolo-
carbazole aglycone 3 of staurosporine. Heterocycle 2
serves as a very strong bidentate ligand in ruthenium
complexes. Additional ligands in the coordination
sphere of the metal substitute for the carbohydrate moi-
ety of staurosporine, with the metal center serving as a
‘glue’ to unite all of the parts. This approach has re-
sulted in the successful design of nanomolar and even
picomolar protein kinase inhibitors.1
O
O
O
O
O
N
N
N
N
N
N
O
Ru
Ru
C
C
O
O
O
NH
Staurosporine
5
1 (R = H), 1Bn (R = Bn)
H
Bn
N
H
N
N
O
O
O
O
O
N
N
N
H
N
H
N
N
H
3
2
4
Figure 1. Staurosporine as
ruthenium-based protein kinase inhibitors.
a lead structure for the design of
We became interested in designing ruthenium complexes
with similar overall structures but modulated electron
density at the metal center. This may allow us to design
kinase inhibitors with additional functions such as lumi-
nescence, reactivity, or catalytic properties, which gener-
ally depend on the electronic nature of all involved
ligands. Toward this goal we here disclose the synthesis
of N-benzyl pyrido[3,2-e]-2,10b-diaza-cyclopenta[c]fluo-
rene-1,3-dione 4, which differs from pyridocarbazole 2
scaffold by the connectivity of the indole moiety. This
heterocycle can serve as a bidentate ligand for ruthe-
nium as demonstrated for complex 5, forming a coordi-
native bond with the pyridine and a covalent bond with
a carbon of the indole moiety.
*
Corresponding author. Tel.: +1 215 573 1953; fax: +1 215 746
0348; e-mail: meggers@sas.upenn.edu
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.10.054

8878
S. P. Mulcahy et al. / Tetrahedron Letters 47 (2006) 8877–8880
Bn
N
Bn
(HO)2B
Bn
N
O
O
N
O
O
9
H
N
2 steps
(ref. 4)
O
O
O
N
N
+
N
Br
a
O
Br
Br
N
6
7
8
10
b
Bn
N
Bn
Bn
N
Bn
N
O
O
N
O
O
O
O
O
O
N
e
d
c
N
N
N
N
O
O
N
N
HN
Tf
12
Ru
4
11
C
O
5
Scheme 1. Reagents and conditions: (a) Pd(dba)2 (10%), PPh3 (20%), Na2CO3 (3.1 equiv), THF/H2O (5:1), 75 ꢁC, 7 h (70%); (b) TBDMSCl
(3 equiv), NaI (4 equiv), MeCN, 0 ꢁC to rt, 12 h (95%); (c) Tf2O (2 equiv), pyridine, 0 ꢁC to rt, 1 h (75%); (d) Pd(PPh3)4 (20%), Et3N (3.1 equiv),
DMF, 85 ꢁC, 15 h (100%); (e) ½CpRuðCOÞðMeCNÞ2ꢀþPF6ꢁ (1.5 equiv), Et3N (1.2 equiv), DMF, 55 ꢁC, 2 h (61%).
The synthesis of heterocycle 4 is an overall six step route
(Scheme 1). Michael addition/elimination of indoline 6
with N-benzyl dibromomaleimide 7 followed by DDQ
oxidation afforded cross-coupling partner 8 according
to a published procedure.4 A Pd-mediated Suzuki
cross-coupling6 reaction in THF/H2O (5:1) with com-
mercially-available boronic acid 95 (1.5 equiv) afforded
the disubstituted maleimide 10 in a 70% yield.7 It was
important in this reaction to first reflux a solution of
the substrates/reagents in THF prior to addition of
H2O, otherwise intractable precipitation of the catalyst
occurred upon heating. The reaction did not proceed,
however, without H2O which is necessary to dissolve
the base. The removal of the methyl group of 10 with
BBr3 resulted in decomposition of the starting material,
but instead demethylation under milder conditions with
NaI/TBDMSCl in MeCN gave pyridone 11 in a high
yield of 95%.8 Formation of triflate 12 was achieved
with 2.0 equiv of Tf2O in pyridine.9 This choice of sol-
vent is necessary to avoid formation of low-yielding
mixtures of O- and N-triflates. An intramolecular Pd-
catalyzed Heck reaction6 was the final key step in the
synthesis of ligand 4.10 Table 1 outlines a variety of con-
ditions used to optimize this intramolecular cyclization.
An initial stoichiometric C–C bond formation with
Pd(OAc)2 led only to decomposition of the starting
material (entry 1). Subsequent catalytic couplings with
Pd(dba)2 or PdCl2(PPh3)2 gave no cyclization product
either (entries 2 and 3). Further couplings with
Pd(PPh3)4 plus KOAc as a base (entry 4) and Pd2(dba)3
plus Et3N (entry 5) gave the desired cyclization product
in modest yields of 23% and 44%, respectively. We final-
ly found that the combination of the electron-rich Pd(0)
catalyst Pd(PPh3)4 in combination with 3.1 equiv Et3N
affords quantitative yields of the Heck coupling product
4 (entry 6). Thus, the right reaction conditions are highly
critical for this intramolecular Heck coupling to occur in
high yields. Ligand 4 is a deep purple solid and has a
limited solubility profile due to its planarity and thus
recrystallization from refluxing ethanol was used to
purify this compound.10
Next, we investigated the ability of 4 to serve as a biden-
tate ligand for ruthenium. Cyclometalation þwith the
ruthenium precursor ½CpRuðCOÞðMeCNÞ2ꢀ PFꢁ6 in
DMF at 55 ꢁC afforded the coordinatively saturated
complex 5 as a green solid.11 A crystal structure of com-
plex 5 is shown in Figure 2.12 The structure demon-
strates that the pyridoazafluorene heterocycle 4 can
indeed serve as a bidentate ligand for ruthenium, having
one classical coordination bond with the pyridine (Ru1–
˚
N19 = 2.15 A) in addition to one covalent r-bond with
Table 1. Optimization of the intramolecular Heck coupling with 12
Entry
Catalyst (equiv)
Base (equiv)
Ligandb (equiv)
Solvent
Temperature (ꢁC)
Yields (%)
1
2
3
4
5
6
Pd(OAc)2 (1.0)
Pd(dba)2 (0.05)
NaOAc (2.0)
Et3N (3.0)
Et3N (1.1)
KOAc (1.1)
Et3N (2.1)
Et3N (3.1)
PPh3 (2.0) Bu4NI (1.0)
dppp (0.06)
None
None
PPh3 (0.2)
None
Dioxane
DMF
DMF
DMF
DMF
DMF
85
85
85
130
85
85
0
0
0
23
44
100
a
PdCl2(PPh3)2 (0.1)
Pd(PPh3)4 (0.05)
a
Pd2(dba)3 (0.1)
Pd(PPh3)4 (0.2)
a dba = dibenzylideneacetone.
b dppp = 1,3-bis(diphenylphosphino)propane.

S. P. Mulcahy et al. / Tetrahedron Letters 47 (2006) 8877–8880
8879
evaluate the effect of this increased electron density for
the design of organoruthenium kinase inhibitors with
modulated physicochemical and reactive properties.
C24
C22
C25
C27
C23
C21
C26
N12
O2
O1
C13
C11
C10
N9
C1
C2
Acknowledgments
C14
C15
We thank the National Institutes of Health for a Grant
(1 R01 GM071695-01A1) and a Chemistry–Biology
Interface Training Grant Fellowship for S.P.M. (T32
GM 071339).
C7
C8
C16
C6
C5
C20
C17
C3
N19
C33
C4
C18
C29
References and notes
Ru1
C28
1. Ruthenium complexes as protein kinase inhibitors:
(a) Zhang, L.; Carroll, P. J.; Meggers, E. Org. Lett.
2004, 6, 521–523; (b) Bregman, H.; Williams, D. S.; Atilla,
G. E.; Carroll, P. J.; Meggers, E. J. Am. Chem. Soc. 2004,
126, 13594–13595; (c) Bregman, H.; Williams, D. S.;
Meggers, E. Synthesis 2005, 1521–1527; (d) Williams, D.
S.; Atilla, G. E.; Bregman, H.; Arzoumanian, A.; Klein, P.
S.; Meggers, E. Angew. Chem., Int. Ed. 2005, 117, 1984–
1987; (e) Bregman, H.; Carroll, P. J.; Meggers, E. J. Am.
O3
C32
C30
C31
Figure 2. Crystal structure of the N-benzylated derivative of ruthe-
nium complex 5. ORTEP drawing with 30% probability thermal
ellipsoids.
´
Chem. Soc. 2006, 128, 877–884; (f) Debreczeni, J. E.;
Bullock, A. N.; Atilla, G. E.; Williams, D. S.; Bregman,
H.; Knapp, S.; Meggers, E. Angew. Chem., Int. Ed. 2006,
45, 1580–1585; (g) Atilla, G. E.; Williams, D. S.; Bregman,
H.; Pagano, N.; Meggers, E. ChemBioChem 2006, 7, 1443–
1450.
˚
the indole moiety (Ru1–C2 = 2.08 A). The coordination
sphere is further filled up with an g5-cyclopentadienyl
and a CO group. With this, the structure is almost
superimposable to the crystal structure of the analogous
isomer 1Bn (Fig. 1).1b Notably, the Ru–C bond with 5
and the Ru–N bond with 1Bn of the indole moieties
2. For bioorganometallic and medicinal organometallic
chemistry, see: (a) Severin, K.; Bergs, R.; Beck, W. Angew.
Chem., Int. Ed. 1998, 37, 1634–1654; (b) Grotjahn, D. B.
Coord. Chem. Rev. 1999, 190, 1125–1141; (c) Jaouen, G.,
Ed. J. Organomet. Chem. 1999, 589, 1–126; (d) Metzler-
Nolte, N. Angew. Chem., Int. Ed. 2001, 40, 1040–1043;
(e) Fish, R. H.; Jaouen, G. Organometallics 2003, 22,
˚
are virtually equidistant (D = 0.03 A).
Complex 5 is stable under neutral and slightly basic con-
dition but decomposes under acidic and Lewis-acidic
conditions with demetalation and recovery of the free
ligand. For example, this has the consequence that puri-
fication by silica gel chromatography must be performed
in presence of a base such as Et3N.11 This is in contrast
to the isomeric pyridocarbazole complexes 1 and 1Bn,
which do not show this acid sensitivity.
2166–2177; (f) Stodt, R.; Gencaslan, S.; Muller, I. M.;
¨
Sheldrick, W. S. Eur. J. Inorg. Chem. 2003, 1873–1882;
(g) Schlawe, D.; Majdalani, A.; Velcicky, J.; Heßler, E.;
Wieder, T.; Prokop, A.; Schmalz, H.-G. Angew. Chem.,
Int. Ed. 2004, 43, 1731–1734; (h) Staveren, Van D. R.;
Metzler-Nolte, N. Chem. Rev. 2004, 104, 5931–5985;
(i) Yan, Y.; Melchart, K.; Habtemariam, M. A.; Sadler,
P. J. Chem. Commun. 2005, 4764–4776; (j) Dyson, P. J.;
Sava, G. Dalton Trans. 2006, 1929–1933; (k) Schatzschne-
ider, U.; Metzler-Nolte, N. Angew. Chem., Int. Ed. 2006,
45, 1504–1507; (l) Stockland, R. A., Jr.; Kohler, M. C.;
Guzei, I. A.; Kastner, M. E.; Bawiec, J. A., III; Labaree,
D. C.; Hochberg, R. B. Organometallics 2006, 25, 2475–
2485.
Compared to complex 1Bn, the isomeric scaffold 5 pro-
vides a significant change in the electronic nature of the
resulting metal complex. A substantial decrease of
22 cmꢁ1 (1927 vs 1949 cmꢁ1) was observed for the CO
stretch vibration in the infrared spectrum between 1Bn
and 5, indicating an increase in electron density at the
metal center of 5. This is presumably due to the stronger
r-donating nature of the indole–carbon ligand of 5 com-
pared to the analogous indole–nitrogen ligand in 1Bn.
The high electron density at this carbon may be also
responsible for the acid sensitivity of 5.
3. For indolocarbazole protein kinase inhibitors, see:
(a) Kase, H.; Iwahashi, K.; Nakanishi, S.; Matsuda, Y.;
Yamada, K.; Takahashi, M.; Murakata, C.; Sato, A.;
Kaneko, M. Biochem. Biophys. Res. Commun. 1987, 142,
436–440; (b) Ruegg, U. T.; Burgess, G. M. Trends
Pharmacol. Sci. 1989, 10, 218–220; (c) Martiny-Baron,
G.; Kazanietz, M. G.; Mischak, H.; Blumberg, P. M.;
Kochs, G.; Hug, H.; Marme, D.; Schachtele, C. J. Biol.
Chem. 1993, 268, 9194–9197; (d) Caravatti, G.; Meyer, T.;
Fredenhagen, A.; Trinks, U.; Mett, H.; Fabbro, D.
Bioorg. Med. Chem. Lett. 1994, 4, 399–404; (e) Prud-
homme, M. Curr. Pharm. Des. 1997, 3, 265–290;
(f) Jackson, J. R.; Gilmartin, A.; Imburgia, C.; Winkler,
J. D.; Marshall, L. A.; Roshak, A. Cancer Res. 2000, 60,
566.
In summary, we have developed a straightforward syn-
thetic strategy to the unique heterocycle 4 and we dem-
onstrated its ability to serve as a chelating ligand in a
ruthenium complex. Compared to the regioisomeric
pyridocarbazole 2, ligand 4 increases the electron den-
sity of the ruthenium center as demonstrated by probing
the vibrational stretch frequency of a CO group in the
coordination sphere of the ruthenium. Future work will

8880
S. P. Mulcahy et al. / Tetrahedron Letters 47 (2006) 8877–8880
4. Lakatosh, S. A.; Luzikov, Y. N.; Preobrazhenskaya, M.
N. Org. Biomol. Chem. 2003, 1, 826–833.
HRMS calcd for C24H17N3O3 (M+Na)+ 418.1167, found
418.1183 (M+Na)+.
5. 2-Methoxy-3-pyridyl boronic acid was either purchased
commercially or synthesized from 2-methoxypyridine:
Thompson, A. E.; Hughes, G.; Batsanov, A. S.; Bryce,
M. R.; Parry, P. R.; Tarbit, B. J. Org. Chem. 2005, 70,
388–390.
9. Synthesis of compound 12: A solution of compound 11
(1.05 g, 2.65 mmol) in pyridine (26.5 mL) was cooled to
0 ꢁC and stirred under Ar. Tf2O (898 lL, 5.31 mmol) was
added dropwise over 30 min, then warmed to rt, and
stirred for another 30 min. The orange mixture was diluted
to 250 mL with H2O and extracted with EtOAc
(3 · 200 mL). The organic layer was washed with aq 10%
HCl (50 mL), brine (50 mL), dried over MgSO4, and
concentrated. The crude residue was dry-loaded onto silica
gel and purified by column chromatography with 4:1
hexanes/EtOAc as the eluent to provide 12 as an orange
foam (1.05 g, 75%): IR (thin film, cmꢁ1) m 3041, 2933,
1710, 1651, 1597, 1464, 1420, 1395, 1356, 1214, 1130, 1076,
894, 855, 747, 599. 1H NMR (DMSO-d6) d (ppm) 8.47
(dd, J = 1.9, 8.5 Hz, 1H), 8.29 (dd, J = 1.9, 7.7 Hz, 1H),
7.75 (dd, J = 4.8, 7.7 Hz, 1H), 7.62 (d, J = 7.8 Hz, 1H),
7.60 (d, J = 3.6 Hz, 1H), 7.43 (d, J = 7.4 Hz, 2H), 7.36
(t, J = 7.7 Hz, 2H), 7.30 (t, J = 7.2 Hz, 1H), 7.10 (t,
J = 7.4 Hz, 1H), 6.88 (d, J = 3.7 Hz, 1H), 6.88 (t, J =
8.4 Hz, 1H), 6.69 (d, J = 8.3 Hz, 1H), 4.86 (s, 2H). 13C
NMR (DMSO-d6) d (ppm) 168.0, 166.0, 152.5, 149.3,
143.2, 136.1, 135.8, 133.9, 129.7, 128.5, 127.9, 127.5, 127.5,
125.0, 122.5, 122.4, 121.2, 119.0, 116.7, 115.6, 112.2, 108.1,
41.6. HRMS calcd for C25H16N3O5SF3 (M+Na)+
550.0660, found 550.0651 (M+Na)+.
´
6. (a) Routier, S.; Coudert, G.; Merour, J.-Y. Tetrahedron
Lett. 2001, 42, 7025–7028; (b) Wang, J.; Soundarajan, N.;
Liu, N.; Zimmermann, K.; Naidu, B. N. Tetrahedron Lett.
´
2005, 46, 907–910; (c) Routier, S.; Peixoto, P.; Merour,
´
´
J.-Y.; Coudert, G.; Dias, N.; Bailly, C.; Pierre, A.; Leonce,
S.; Caignard, D.-H. J. Med. Chem. 2005, 48, 1401–1413;
´
(d) Routier, S.; Merour, J.-Y.; Dias, N.; Lansiaux, A.;
Bailly, C.; Lozach, O.; Meijer, L. J. Med. Chem. 2006, 49,
789–799.
7. Synthesis of compound 10: To a solution of compound 8
(1.58 g, 4.15 mmol) in THF (125 mL) were added
compound
9 (0.95 g, 6.22 mmol), Na2CO3 (1.21 g,
11.40 mmol), PPh3 (220 mg, 0.83 mmol), and Pd(dba)2
(238 mg, 0.42 mmol), and the resulting solution was purged
with Ar for 10 min and then refluxed. After 1 h, H2O was
added and heated to 75 ꢁC for an additional 6 h and then
cooled to rt. The mixture was poured into 250 mL of H2O
and extracted with EtOAc (3 · 200 mL), washed with brine
(100 mL), and dried over MgSO4. Purification by column
chromatography was performed on silica gel with 20:1
hexanes/EtOAc as the eluent to give disubstituted male-
imide 10 as a viscous orange oil (1.2 g, 70%): IR (thin film,
cmꢁ1) m 3031, 2929, 1705, 1644, 1573, 1457, 1396, 1351,
1204, 1118, 1011, 743. 1H NMR (DMSO-d6) d (ppm) 8.15
(dd, J = 1.8, 4.9 Hz, 1H), 8.07 (dd, J = 1.8, 7.5 Hz, 1H),
7.61 (d, J = 3.6 Hz, 1H), 7.60 (d, J = 8.3 Hz, 1H), 7.40
(d, J = 7.1 Hz, 2H), 7.36 (t, J = 7.8 Hz, 2H), 7.30 (t,
J = 7.1 Hz, 1H), 7.17 (dd, J = 4.9, 7.5 Hz, 1H), 7.05
(t, J = 7.3 Hz, 1H), 6.82 (d, J = 3.6 Hz, 1H), 6.82 (t,
J = 7.3 Hz, 1H), 6.59 (d, J = 8.3 Hz, 1H), 4.79 (s, 2H), 2.89
(s, 3H). 13C NMR (DMSO-d6) d (ppm) 169.1, 166.9, 160.3,
148.4, 140.3, 136.5, 134.6, 133.3, 129.1, 128.6, 128.4, 127.7,
127.5, 122.1, 121.6, 120.8, 119.2, 116.9, 111.9, 111.7, 106.6,
52.9, 41.5. HRMS (CI) calcd for C25H19N3O3 (M)+
409.1426, found (M)+ 409.1426.
10. Synthesis of compound 4: A solution of compound 12
(150 mg, 0.3 mmol) in dry DMF (3.7 mL) was treated with
Et3N (123 lL, 0.9 mmol). After the addition of Pd(PPh3)4
(60 mg, 0.06 mmol), the solution was purged with Ar
10 min, and then heated to 85 ꢁC for 15 h. The purplish-
red mixture was cooled to rt and diluted with 100 mL
CH2Cl2. The organic extract was washed with brine
(2 · 20 mL), dried over MgSO4, and concentrated. Recrys-
tallization from refluxing EtOH gave 4 as a purple solid
(160 mg, 100%): IR (thin film, cmꢁ1) m 1688, 1624, 1583,
1556, 1478, 1446, 1396, 1341, 1322, 1222, 1131, 953, 815,
1
779, 742. H NMR (CDCl3) d (ppm) 9.41 (m, 1H), 8.89
(dd, J = 1.7, 8.1 Hz, 1H), 8.84 (dd, J = 1.7, 4.6 Hz, 1H),
7.89 (m, 1H), 7.87 (s, 1H), 7.71 (m, 2H), 7.46 (dd, J = 4.6,
8.1 Hz, 1H), 7.34–7.52 (m, 5H), 4.92 (s, 2H). HRMS (ESI)
calcd for C24H15N3O2 378.1242 (M+H)+, found (M+H)+
378.1250.
8. Synthesis of compound 11: A solution of compound 10
(250 mg, 0.61 mmol) in MeCN (73 mL) was cooled to
0 ꢁC, purged with Ar, then treated with anhydrous NaI
(366 mg, 2.45 mmol) and TBDMSCl (276 mg, 1.83 mmol)
sequentially, and subsequently slowly warmed to rt. An
orange suspension slowly evolved and the mixture was
stirred for 12 h. The mixture was quenched with H2O and
extracted into 200 mL EtOAc. The organic layer was
washed with aq 5% NaHCO3 (2 · 75 mL), brine
(2 · 75 mL), dried over MgSO4, and concentrated. The
crude residue was purified by column chromatography on
silica gel with 200:1 CH2Cl2/MeOH as the eluent to afford
11 as an orange foam (230 mg, 95%): IR (thin film, cmꢁ1) m
3037 (br), 2857, 1701, 1633, 1552, 1454, 1431, 1395, 1355,
1242, 1206, 1118, 1053, 742. 1H NMR (DMSO-d6) d (ppm)
7.89 (dd, J = 1.0, 7.0 Hz, 1H), 7.63 (d, J = 3.5 Hz, 1H),
7.57 (d, J = 8.1 Hz, 1H), 7.47 (dd, J = 1.0, 6.1 Hz, 1H),
7.39 (d, J = 5.7 Hz, 2H), 7.36 (t, J = 7.7 Hz, 2H), 7.29
(t, J = 6.8 Hz, 1H), 7.08 (t, J = 6.8 Hz, 1H), 6.96 (m,
J = 6.8, 7.5 Hz, 1H), 6.94 (d, J = 8.1 Hz, 1H), 6.74 (d,
11. Synthesis of complex 5: A solution of compound 4 (10 mg,
0.027 mmol) in dry DMF (1.8 mL) was treated with Et3N
(4.4 lL, 0.032 mmol) and ½CpRuðCOÞðMeCNÞ2ꢀþPF6ꢁ
(17 mg, 0.04 mmol) and heated to 55 ꢁC for 2 h. The
resulting greenish-brown mixture was diluted with 20 mL
EtOAc, washed with brine (20 mL), dried over MgSO4,
and concentrated. Purification by column chromatogra-
phy on silica gel with 50:1:0.01 hexanes/EtOAc/Et3N as
the eluent afforded 5 as a green solid (9 mg, 61%): IR (thin
film, cmꢁ1) m 3078, 2930, 1927, 1706, 1564, 1540, 1466,
1432, 1393, 1123, 805, 743. 1H NMR (DMSO-d6) d (ppm)
9.04 (m, 1H), 8.89 (dd, J = 1.1, 5.6 Hz, 1H), 8.28 (dd,
J = 1.1, 7.7 Hz, 1H), 7.99 (m, 1H), 7.53 (m, 2H), 7.27–7.41
(m, 5H), 7.19 (dd, J = 5.6, 7.7 Hz, 1H), 5.31 (s, 5H), 4.92
(s, 2H).
12. Crystals were grown by the slow evaporation of a solution
of 5 in MeCN to give an opaque green solid suitable for X-
ray crystallographic analysis. CCDC 621757 contains the
supplementary crystallographic data for this paper. These
data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
J = 3.5 Hz, 1H), 6.37 (t, J = 6.8 Hz, 1H), 4.73 (s, 2H). 13
C
NMR (DMSO-d6) d (ppm) 169.2, 167.1, 158.8, 143.3,
137.6, 136.6, 135.2, 133.0, 128.9, 128.6, 128.5, 127.6, 127.5,
122.0, 121.3, 120.8, 120.2, 119.8, 111.8, 106.3, 104.9, 41.4.