The first organo-tungsten pyrylium salt and structural characterization of its pseudobase

Article abstract of DOI:10.1039/b104419m

The first example of an organo-tungsten pyrylium complex (4-cyclopentadienyl-2,6-diphenylpyrylium)W(CO)₃CH₃ has been prepared, fully characterized and transformed in an aqueous basic medium to the corresponding pseudobase (3-cyclopen

Full text of DOI:10.1039/b104419m

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The first organo-tungsten pyrylium salt and structural
characterization of its pseudobase
Pierre Haquette,a Michèle Salmain,a Yann Marchal,a Yoann Marsac,a Gérard Jaouen,*a Desmond
Cunningham,b Darren P. Eganb and Patrick McArdle*b
a Laboratoire de Chimie Organométallique, UMR CNRS 7576, Ecole Nationale Supérieure de Chimie de
Paris, 11, rue Pierre et Marie Curie F-75231. Paris cedex 05, France. E-mail: jaouen@ext.jussieu.fr
b Department of Chemistry, National University of Ireland, Galway, Ireland
Received (in Cambridge, UK) 18th May 2001, Accepted 28th June 2001
First published as an Advance Article on the web 18th July 2001
The first example of an organo-tungsten pyrylium complex
(4-cyclopentadienyl-2,6-diphenylpyrylium)W(CO)3CH3 has
been prepared, fully characterized and transformed in an
aqueous basic medium to the corresponding pseudobase
(3-cyclopentadienyl-1,5-diphenylpent-2-ene-1,5-dione)W-
(CO)3CH3 which is the first X-ray structure analysed
organometallic pseudobase.
Complex 3 was isolated as a deep purple air stable solid in
30% overall yield and characterized by elemental analysis, IR
and H and 13C{1H} NMR spectroscopies. In the H NMR
spectrum, a characteristic resonance at 8.79 (s) ppm was
assigned to the two pyrylium protons. The 13C{1H} NMR
spectrum exhibited three signals at 113.5, 164.1 and 171.2 ppm
assignable to Cb, Cg and Ca, respectively, of the heterocycle.
These data are very similar to those of 2,4,6-triphenylpyrylium
salt9 and show no significant influence of the organometallic
fragment on the heterocycle carbon chemical shifts.
1
1
It has been shown recently1–3 that pyrylium salts bearing an
organometallic fragment are very promising candidates for the
labeling of biological molecules. Due to their electrophilicity,
this family of compounds could be attractive for the selective
introduction of heavy atoms into protein crystals by means of
covalent bond formation with protein side chains carrying a
primary amine. Since such heavy metal protein derivatives are
required for crystallographic phase determination when using,
for example, the multiple isomorphous replacement method
(MIR),4 organometallic pyrylium salts could potentially be of
great use for three-dimensional protein structure determination
by X-ray crystallography. Several synthetic approaches have
been suggested for the preparation of organometallic pyrylium
salts bearing benchrotrenyl,1,5 ferrocenyl,6 cyclopentadienyl-
tricarbonyl-manganese1,7 or -rhenium1 fragments at the 4-posi-
tion of the heterocyclic ring. Reactivity studies using bench-
rotrenyl pyrylium salts with primary amines, amino acids or
proteins have shown that labeling was observed even using
crystalline protein.8 Nevertheless, X-ray diffraction experi-
ments indicated the need for heavier atoms with larger
electronic densities. We therefore sought to develop derivatives
of the CpW(CO)3CH3 system which are both air and light stable
and provide a heavy metal in a suitable organometallic
environment.
The mechanism of pyrylium to pyridinium conversion has
been thoroughly studied.10 Kinetic measurements using UV–
visible spectroscopy performed on a series of 4-benchrotrenyl
pyrylium salts indicated that in aqueous media, and especially at
basic pH, the hydrolysis of the pyrylium salt is very fast and that
the pseudobase form (open chain diketone form) resulting from
the addition of OH2 to the pyrylium salt is in fact the reactive
species that undergoes the nucleophilic addition by the protein
amino group (Scheme 2).3 Thus, knowledge of the structure and
reactivity of the pseudobase form of pyrylium complex 3 is
important for the understanding of the mechanism of protein
labelling by these species.
Treatment of the tungsten pyrylium salt 3 with Na2CO3 in an
acetone–water mixture and subsequent extraction with diethyl
ether led to the corresponding pseudobase ((3-cyclopentadie-
nyl-1,5-diphenylpent-2-ene-1,5-dione)W(CO)3CH3) 4 in 92%
yield (Scheme 1) as a moderately air stable yellow solid.†
The structure of 4 was established by 1H NMR analysis
which revealed the presence of methylenic and vinylic protons
at 4.51 and 7.24 ppm, respectively. The carbon atoms of the
pent-2-ene-1,5-dione chain gave signals at 195.7 (CNO), 190.3
(conjugated CNO), 144.4 and 121.2 (CNC) and 41.7 (CH2) ppm
We now report the synthesis of the first pyrylium salt
containing a tungsten organometallic moiety and the X-ray
structural analysis of the pseudobase obtained from its hydroly-
sis under basic conditions.
The tungsten pyrylium complex 3 was obtained by reaction
of deprotonated starting material 1 with preformed 2,6-di-
phenylpyrylium salt followed by hydride abstraction from the
resulting pyran derivative with trityl cation (Scheme 1).†
Scheme
1
Reagents and conditions: i, BunLi, THF, 278 °C; ii,
2,6-diphenylpyrylium salt, THF, 278 °C to RT; iii, Ph3C+BF42, CH3CN,
Scheme 2 Reaction of a protein with a pyrylium salt in basic aqueous
medium.
RT; iv, Na2CO3, acetone/H2O/ether, RT.
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Chem. Commun., 2001, 1504–1505
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b104419m

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mixture was stirred for 10 min at RT during while the organic phase turned
orange. After extraction with diethyl ether (10 ml), evaporation and addition
of pentane to the resulting oil, the pseudobase 4 was obtained as a yellow
powder (110 mg, 0.184 mmol, 92%). Selected data for 4: n(CH2Cl2)/
cm21 1922, 2017 (C·O); dH(200 MHz, CDCl3): 0.51 (s, 3H, CH3), 4.51 (s,
2H, CH2), 5.49 (t, 2H, J = 2.4 Hz, Cp), 5.59 (t, 2H, J = 2.4 Hz, Cp), 7.24
(s, 1H, –CHN), 7.67–7.43 (m, 6H, Ph), 7.91 (d, 2H, J = 8.5 Hz, Ph), 8.09
(d, 2H, J = 8.5 Hz, Ph); dC(100 MHz, CDCl3): 230.9 (CH3), 41.7 (C4),
90.1 (C2,2A-Cp), 92.5 (C3,3A-Cp), 109.4 (C1-Cp), 121.2 (C2), 128.3, 128.4,
128.7, 128.9 (Cortho,meta-Ph), 133.0, 133.6 (Cpara-Ph), 136.5 (Cipso-Ph),
138.8 (Cipso-Ph), 144.4 (C3), 190.3 (C1), 195.7 (C5), 215.1 (C·O), 227.6
(C·O); Elemental anal. Calc. for C26H20O5W: C, 52.36; H, 3.36. Found: C,
52.84; H, 3.54%.
‡ Crystal data for C26H20O5W (4): The compound crystallises in the
¯
triclinic space group P1; Mr = 596.27, a = 9.952(2), b = 10.753(3), c =
Fig. 1 The molecular structure of 4. Selected bond lengths (Å) and angles
(°); C(5)–C(10) 1.424(9), C(10)–C(19) 1.325(10), C(19)–C(20) 1.473(9),
C(20)–O(5) 1.227(9), C(20)–C(21) 1.484(10); C(6)–C(5)–C(10) 126.5(7),
C(5)–C(10)–C(19) 119.3(6), C(10)–C(19)–C(20) 124.7(6), C(19)–C(20)–
O(5) 122.4(7), C(19)–C(20)–C(21) 118.1(6), C(5)–C(10)–C(11) 117.0(6),
C(10)–C(11)–C(12) 112.6(6), C(11)–C(12)–O(4) 120.8(8), C(11)–C(12)–
C(13) 118.4(6).
12.567(3) Å, a = 66.63(2), b = 71.183(19), g = 63.35(2)°, U = 1086.2(4)
Å3, Z = 2, T = 293(2) K, m = 5.353 mm21, Dc = 1.823 Mg m23, F(000)
= 580, Of a total of 6921 collected reflections, 6315 were unique (R(int) =
0.0325) and used in all calculations. The final wR2 = 0.1622 (all data),
R1 [I > 2s(I)] = 0.0755. The structure was solved by direct methods,
SHELXS-97,14 and refined by full matrix least squares using SHELXL-
97.15 SHELX operations were automated using ORTEX which was also
used to obtain the drawings.16 Data were corrected for Lorentz, polarization
effects and for absorption by the method of Y scans. The minimum
transmission was 74%.17 Hydrogen atoms were included in calculated
positions with thermal parameters 30% larger than the atom to which they
are attached. The non-hydrogen atoms were refined anisotropically. All
calculations were performed on a Pentium PC. CCDC reference number
number 166487. See http://www.rsc.org/suppdata/cc/b1/b104419m/ for
crystallographic data in CIF or other electronic format.
in the 13C{1H} NMR spectrum. These spectroscopic data are
very similar to those of the corresponding compound bearing a
phenyl group instead of the organo-tungsten fragment11 except
for the carbon C3 signal which is shifted 8 ppm upfield.
The structure of pseudobase 4 was confirmed by X-ray
crystallography (Fig. 1).‡ The complex exhibits a four-legged
piano stool geometry with the methyl group on tungsten and the
substituent on the Cp in perpendicular vertical planes. Bond
distances within the diketone chain are in agreement with those
reported for the only structurally characterized pseudobase
PhC(O)CHNC(CF3)CH2C(O)Ph12 which bears a CF3 sub-
stituent in place of the Cp-tungsten fragment. The dihedral
angles along the conjugated chain (C(6)–C(5)–C(10)–C(19)
18.6°; C(10)–C(19)–C(20)–O(5) 21.2°; O(5)–C(20)–C(21)–
C(26) 18.7°) show significant deviation from planarity and the
two phenyl end groups are almost perpendicular to each
other.
1 K. L. Malisza, S. Top, J. Vaissermann, B. Caro, M.-C. Sénéchal-
Tocquer, D. Sénéchal, J.-Y. Saillard, S. Triki, S. Kahlal, J. F. Britten, M.
J. McGlinchey and G. Jaouen, Organometallics, 1995, 14, 5273.
2 M. Salmain, K. L. Malisza, S. Top, G. Jaouen, M.-C. Sénéchal Tocquer,
D. Sénéchal and B. Caro, Bioconjugate Chem., 1994, 5, 655.
3 B. Caro, F. Le Guen-Robin, M. Salmain and G. Jaouen, Tetrahedron,
2000, 56, 257.
4 T. L. Blundell and L. N. Johnson, Protein Crystallography, Academic
Press, New York, 1976, pp. 173–259.
5 B. Caro, M.-C. Sénéchal-Tocquer, D. Sénéchal and P. Marrec,
Tetrahedron Lett., 1993, 34, 7259.
6 (a) G. N. Dorofeenko, V. V. Krasnikov and A. I. Pyshchev, Khim.
Geterotskl. Soedin., 1977, 599; Chem. Abstr., 1977, 87, 85121; L. Yu.
Ukhin, A. I. Pyshchev, V. V. Krasnikov, Zh. I. Orlova and G. N.
Dorofeenko, Dokl. Akad. Nauk SSSR, 1977, 234, 1351; Chem. Abstr.,
1977, 87, 168162; (c) V. V. Krasnikov, Yu. P. Andreichikov, N. V.
Kholodova and G. N. Dorofeenko, Zh. Org. Khim., 1977, 13, 1566;
Chem. Abstr., 1977, 87, 152357.
7 (a) V. V. Krasnikov and G. N. Dorofeenko, Khim. Geterotsikl. Soedin.,
1979, 21; Chem. Abstr., 1979, 80, 168702 (b) G. N. Dorofeenko and V.
V. Krasnikov, Zh. Org. Khim., 1972, 8, 2620; Chem. Abstr., 1973, 78,
97785; A. G. Milaev and O. Yu. Okhlobystin, Khim. Geterotsikl.
Soedin., 1985, 593; Chem. Abstr., 1986, 104, 68978.
8 D. P. Egan, P. McArdle, M. Salmain and G. Jaouen, unpublished
work.
The kinetics of reaction of complex 3 with n-butylamine in
acetonitrile was studied spectrophotometrically. Conversion to
the N-butylpyridinium salt followed a pseudo-first order
reaction rate with kobs = 5.4 3 1024 s21. The structure of the
1
final product was confirmed by H NMR. For comparison, in
the same experimental conditions, a kobs of 0.58 3 1024 s21 and
0.32 3 1024 s21 was measured for 4-benchrotrenyl-2,6-di-
phenylpyrylium tetrafluoroborate and 2,4,6-triphenylpyrylium
tetrafluoroborate, respectively.3,13
This synthesis may help provide a new approach in X-ray
structural determination of proteins.
This work was supported by the European COST D8/0016
action.
9 A. R. Katritzky, R. T. C. Brownlee and G. Musumarra, Heterocycles,
1979, 12, 775.
Notes and references
10 A. T. Balaban, G. W. Fischer, A. Dinulescu, A. V. Koblik, G. N.
Dorofeenko, V. V. Mezhritski and W. Schroth, Adv. Heterocycl. Chem.,
Suppl. II, ed. A. R. Katritzky, Academic Press, New York, 1982.
11 A. R. Katritzky, R. T. C. Brownlee and G. Musumarra, Tetrahedron
Lett., 1980, 1643.
12 R. G. Pritchard, S. Tajammal and A. E. Tipping, Acta Crystallogr., Sect.
C , 1994, 50, 294.
13 A. R. Katritzky and R. H. Manzo, J. Chem. Soc., Perkin Trans., 1981,
2, 571.
14 G. M. Sheldrick, Acta Crystallogr., Sect. A, 1990, 46, 467.
15 G. M. Sheldrick, SHELXL-97: a computer program for crystal structure
determination, University of Göttingen, 1997.
† Synthetic procedure for 3: to a solution of the pyran complex 2 (232 mg,
–
0.4 mmol) in acetonitrile (10 mL) was added Ph3C+BF4 (170 mg, 0.45
mmol). The solution was stirred for 0.5 h at RT. On addition of diethyl ether
(30 ml), complex 3 precipitated as a deep purple solid (205 mg, 0.29 mmol,
72%). Selected data for 3: n(CH2Cl2)/cm21 1936, 2026 (C·O); dH(200
MHz, d6-acetone): 0.54 (s, 3H, CH3), 6.28 (t, 2H, J = 2.4 Hz, Cp), 6.93 (t,
2H, J = 2.4 Hz, Cp), 7.93–7.75 (m, 6H, Ph), 8.54 (m, 4H, Ph), 8.79 (s, 2H,
H3,5-pyr); dC(100 MHz, d6-acetone) 230.8 (CH3), 93.8 (C2,2A-Cp), 98.3
(C1-Cp), 99.6 (C3,3A-Cp), 113.50 (C3,5-pyr), 129.3 (Cortho-Ph), 130.1 (Cipso
-
Ph), 130.8 (Cmeta-Ph), 135.9 (Cpara-Ph), 164.1 (C4-pyr), 171.2 (C2,6-pyr),
214.5 (C·O), 226.1 (C·O); Elemental anal. Calc. for C26H19BF4O4W: C,
46.87; H, 2.85. Found: C, 46.76; H, 2.91%. Synthetic procedure for 4: to a
solution of the pyrylium complex 3 (143 mg, 0.2 mmol) in acetone (5 ml)
and ether (5 ml) was added K2CO3 (70 mg, 2 mmol) in water (3 ml). The
16 P. McArdle, J. Appl. Crystallogr., 1995, 28, 65.
17 A. C. T. North, D. C. Phillips and F. S. Mathews, Acta Crystallogr.,
Sect. A, 1968, 24, 351.
Chem. Commun., 2001, 1504–1505
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