Synthesis and evaluation of 5-phenyl- 1H-1,4-benzodiazepin-2 (3H) -one-based palladium complexes as precatalysts in C-C bond forming reactions

Article abstract of DOI:10.1021/om0506623

The C-H activation of C-3-unsubstituted 1,4-benzodiazepin-2(3H)-ones (LH = 2a-c) (2a = 1-methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one, 2b = 1-benzyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one, 2c = benzyl-2-(2,3-dihydro-2- oxo-5-phenyl-1,4-benzodiazepin-1-

Full text of DOI:10.1021/om0506623

Organometallics 2005, 24, 5665-5672
5665
Synthesis and Evaluation of
5-Phenyl-1H-1,4-benzodiazepin-2(3H)-one-Based
Palladium Complexes as Precatalysts in C-C Bond
Forming Reactions
John Spencer,*,† David P. Sharratt,† Jairton Dupont,‡ Adriano L. Monteiro,‡
Vinicius I. Reis,‡ Marcelo P. Stracke,‡ Frank Rominger,§ and Iain M. McDonald†
James Black Foundation, 68 Half Moon Lane, London, SE24 9JE, U.K., Laboratory of
Molecular Catalysis, IQ-UFRGS, Avenida Bento Gonc¸alves, 9500, Porto-Alegre 91501-970 RS,
Brazil, and Organisch-Chemishes Institut der Ruprecht-Karls-Universita¨t Heidelberg, Im
Neuenheimer Feld 270, D-69120 Heidelberg, Germany
Received August 1, 2005
The C-H activation of C-3-unsubstituted 1,4-benzodiazepin-2(3H)-ones (LH ) 2a-c) (2a
) 1-methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one, 2b ) 1-benzyl-5-phenyl-1H-1,4-ben-
zodiazepin-2(3H)-one, 2c ) benzyl-2-(2,3-dihydro-2-oxo-5-phenyl-1,4-benzodiazepin-1-yl)-
acetate) with Na2PdCl4 afforded the insoluble palladacycles [(L)PdCl]2 3a-c. Treatment of
the latter with triphenylphosphine afforded the soluble monomeric triphenylphosphine
analogues [(L)Pd(PPh3)Cl] 4a-c. 1-Methyl-3-(2-(methylthio)ethyl)-5-phenyl-1H-1,4-benzo-
diazepin-2(3H)-one (LH ) 2d) reacted with Na2PdCl4 or with PdCl2(MeCN)2 to afford the
monomeric cis-S-N-coordinated complex 5d of the type [(LH)PdCl2]. 3-((tert-Butylthio)-
methyl)-1-methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one, 2e, reacted with Pd(OAc)2 in
acetic acid and, following LiCl metathesis, yielded the monomeric cis-S-N-bound pincer
palladacycle 6f. X-ray structures of 5d and 4a have been determined. 3a and 6f were found
to be effective precatalysts for Suzuki coupling reactions, and 3a, 3c, and 4a were effective
precatalysts in Heck couplings across a range of substrates.
Introduction
important 1,4-benzodiazepine skeleton has been studied
in detail,5 and it has been shown to act as a bidentate
or monodentate ligand toward palladium. For example,
the palladacycle A resulted from the C-H activation of
the C(5) phenyl group in Valium using Na2PdCl4 as
metallating agent, whereas the coordination complex B
was synthesized using Prazepam as ligand and PdCl2-
(PhCN)2 as palladium source. Complex A was employed
in a carbonylation reaction yielding the novel hetero-
cycles C (Scheme 1).5a,b
Palladacycles are a fascinating family of organome-
tallic complexes with applications in many areas includ-
ing total synthesis, materials science, and biological and
supramolecular chemistry.1 Moreover, they are often air
stable, are readily synthesized, and possess a range of
structures, ring sizes, types of metalated carbon (sp2
aromatic or vinylic, sp3), and different types of donor
groups bound to palladium (P-, N-, S-, O-, Se-containing
groups) (Figure 1). The stoichiometric applications of
palladacycles in organic synthesis have been reviewed,2
and an increasing number of attractive high turnover
number (TON) catalytic applications are now known.3,4
The coordination chemistry of the pharmaceutically
We recently prepared a range of C-3-unsubstituted
1,4-benzodiazepine ligands as precursors to imine-bound
palladacycles related to A employing similar C-H
(4) (a) Xiong, Z.; Wang, N.; Dai, M.; Li, A.; Chen, J.; Yang, Z. Org.
Lett. 2004, 6, 3337. (b) Botella, L.; Najera, C. Tetrahedron 2004, 60,
5563. (c) Schnyder, A.; Indolese, A. F.; Studer, M.; Blaser, H. U. Angew.
Chim. Int. Ed. 2002, 41, 3668 (d) Yao, Q.; Kinney, E. P.; Zheng, C.
Org. Lett. 2004, 6, 2997. (e) Roca, F. X.; Richards, C. J. Chem. Commun.
2003, 3002. (f) Thakur, V. V.; Ramesh Kumar, N. S. C.; Sudalai, A.
Tetrahedron Lett. 2004, 45, 2915. (g) Chen, C.-L.; Liu, Y. H.; Peng, S.
M.; Liu, S.-T. Organometallics 2005, 24, 1075. (h) Eberhard, M. R. Org.
Lett. 2004, 6, 2125. (i) Bielsa, R.; Larrea, A.; Navarro, R.; Soler, T.;
Urriolabeitia, E. P. Eur. J. Inorg. Chem. 2005, 1724. (j) Rocaboy, C.;
Gladysz, J. A. New J. Chem. 2003, 27, 39.
(5) (a) Cinellu, M. A.; Gonadu, M. L.; Minghetti, G.; Cariati, F.;
Manasserro, M. Inorg. Chim. Acta 1988, 143, 197. (b) Cinellu, M. A.;
Gladiali, S.; Minghetti, G.; Stoccorro, S.; Demartin, F. J. Organomet.
Chem. 1991, 401, 371. (c) Perez, J.; Riera, V.; Rodriguez, A.; Miguel,
D. Organometallics 2002, 21, 5437. (d) Visnjevac, A.; Tusek,-Bozic, L.;
Majeric-Elenkov, M.; Hamersak, Z.; Kooijman, H.; De Clercq, E.; Kojic-
Prodic, B. Polyhedron 2002, 21, 2567. (e) Antolini, L.; Bruno, G.;
Cusumano, M.; Giannetto, A.; Ficarra, P.; Ficarra, R. Polyhedron 1992,
11, 2795. (f) Cusumano, M.; Giannetto, A.; Ficarra, P.; Ficarra, R. J.
Chem. Soc., Dalton Trans. 1991, 1581. (g) Stoccoro, S.; Cinellu, M. A.;
Zucca, A.; Minghetti, Demartin, F. Inorg. Chim. Acta 1994, 215, 17.
* Corresponding author. Fax
john.spencer@kcl.ac.uk.
+
44-207-2749687. E-mail:
† James Black Foundation.
‡ Laboratory of Molecular Catalysis, IQ-UFRGS.
§ Organisch-Chemishes Institut der Ruprecht-Karls-Universita¨t
Heidelberg.
(1) Dupont, J.; Consorti, C. S.; Spencer, J. Chem. Rev. 2005, 105,
2527.
(2) (a) Ryabov, A. D. Synthesis 1985, 233. (b) Spencer, J.; Pfeffer,
M. Adv. Met. Org. Chem. 1998, 6, 103. (c) Omae, I. Coord. Chem. Rev.
2004, 248, 995.
(3) Reviews: (a) Herrmann, W. A.; Bohm, V. P. W.; Reisinger, C. P.
J. Organomet. Chem. 1999, 576, 23. (b) Bedford, R. B. Chem Commun.
2003, 1787. (c) Dupont, J.; Pfeffer, M.; Spencer, J. Eur. J. Inorg. Chem.
2001, 1917. (d) van der Boom, M. E.; Milstein, D. Chem. Rev. 2003,
103, 1759. (e) Beletskaya, I. P.; Cheprakov, A. V. J. Organomet. Chem.
2004, 689, 4055. (f) Farina, V. Adv. Synth. Catal. 2004, 346, 1553. (g)
Bellina, F.; Carpita, A.; Rossi, R. Synthesis 2004, 15, 2419. (h) Zapf,
A.; Beller, M. Chem. Commun. 2005, 431. (i) Bedford R. B.; Cazin, C.
S. J.; Holder, D. Coord. Chem. Rev. 2004, 248, 2283.
10.1021/om0506623 CCC: $30.25 © 2005 American Chemical Society
Publication on Web 10/05/2005

5666 Organometallics, Vol. 24, No. 23, 2005
Spencer et al.
Figure 1. Examples of palladacycles employed in catalysis.
Scheme 1. Palladium-Containing 1,4-Benzodiazepine Complexes and a Carbonylation Reaction
activation reactions. Intrigued by the possibility of a
tridentate binding mode to palladium, C-3-substituted
1,4-benzodiazepine ligands were synthesized by intro-
ducing a side chain containing a thioether group,
derived from either cysteine or methionine. Herein we
present results pertaining to the synthesis of 1,4-
benzodiazepine-containing palladium complexes, their
structural characterization in both solution and the solid
state, and their application in catalysis.
hydride and reaction with the requisite alkyl halides,
1
affording 2a-e, which were characterized by H, 13C
NMR and LCMS (Scheme 2).
Palladium Complexes. Treatment of 2a-c with
Na2PdCl4 in ethanol resulted in the formation of yellow
or beige precipitates. Due to their low solubility, it was
not possible to satisfactorily characterize these products
by 1H NMR spectroscopy. However, their treatment
with triphenylphosphine afforded soluble products,
whose spectral properties, particularly the shielded
1
aromatic protons in their H NMR spectra, character-
Results and Discussion
istic of a metalated phenyl group cis to PPh3, and a 31
P
1,4-Benzodiazepine Synthesis. The 1,4-benzodi-
azepines 1a-e were made by a modification of the
reported methods (EEDQ ) 2-ethoxy-1-ethoxycarbonyl-
1,2-dihydroquinoline).6 Alkyl substituents at the N-1
position were introduced by treatment with sodium
NMR singlet at ca. 41 ppm, were consistent with the
monomeric structures 4a-c.7 By inference, the original
precipitates were assigned the dimeric structures 3a-
c, which were, moreover, consistent with the combustion
data obtained (Scheme 3).
The solid-state structure of the palladacycle 4a was
determined by an X-ray study of crystals obtained
from a dichloromethane/hexane mixture. The pallada-
cycle was found to have a distorted square planar
configuration, probably as a result of steric encumbrance
from the triphenylphosphine ligand, resulting in a
C1-Pd-Cl1 bond angle of 171.84(7)° and a N1-Pd-
P1 angle of 174.92(6)° (Table 1, Figure 2). Bond lengths
in 4a were found to be similar to those in related
(6) (a) Stafford, J. A.; Pacofsky, G. J.; Cox, R. F.; Cowan, J. R.;
Dorsey, G. F.; Gonzales, S. S.; Jung, D. K.; Koszalka, G. W.; McIntyre,
M. S.; Tidwell, J. H.; Wiard, R. P.; Feldman, P. L. Bioorg. Med. Chem.
Lett. 2002, 12, 3215. (b) Clarke, G. M.; Lee, G. M.; Swinbourne, F. J.;
Williamson, B. J. Chem. Res. 1980, 12, 4777. (c) Carpino, L. A.; Cohen,
B. J.; Stephens, K. E., Jr.; Sadat-Aalaee, S. Y.; Tien, J. H.; Langridge,
D. C. J. Org. Chem. 1986, 51, 3732. (d) Marc, G.; Pecar, S. Synth.
Commun. 1998, 28, 1143, and references therein.
(7) Dunina, V. V.; Kuz’mina, L. G.; Rubina, M. Y.; Grishin, Y. K.;
Veits, Y. A.; Kazakova, E. I. Tetrahedron: Asymmetry 1999, 10, 1483,
and references therein.

Benzodiazepine-Based Palladium Complexes
Organometallics, Vol. 24, No. 23, 2005 5667
Scheme 2. 1,4-Benzodiazepine Synthesis
Scheme 3. 1,4-Benzodiazepine Palladation
Scheme 4. Synthesis of the Coordination
Complex 5d
Table 1. Selected Bond Lengths (Å) and Angles
(deg) for 4a
Treatment of the sulfur-containing 1,4-benzodiazepine
2d with Na2PdCl4, according to the same conditions
used to obtain 3a-c, afforded a precipitate, which was
sufficiently soluble for 1H NMR characterization. In the
product, S-Pd coordination was evidenced by a signifi-
Bond Lengths
Pd1-C1
Pd1-N1
Pd1-P1
Pd1-Cl1
2.015(2)
P1-C11
N1-C7
N1-C8
N2-C9
1.835(3)
1.297(3)
1.464(3)
1.362(3)
2.0816(19)
2.2653(6)
2.3602(7)
1
cant H NMR downfield shift of the SMe signal (δ )
2.76 ppm) compared with the free ligand (δ ) 2.06
ppm).8 An identical product was obtained after treat-
ment of 2d with PdCl2(MeCN)2, suggesting the chelated-
monomeric structure 5d, which was unequivocally
determined by a single-crystal X-ray structure measure-
ment (Scheme 4, Figure 3).
Crystals of 5d were grown from a chloroform/hexane
mixture and were found to be racemic and to contain a
molecule of chloroform in the asymmetric unit. The unit
cell contains eight molecules of CHCl3. There is no Pd-C
bond, and the metal is part of a six-membered boat-
shaped ring with a cis-S,N arrangement (Figure 3 and
Table 2). The Pd-Cl bond lengths of around 2.33 Å are
as expected. In the absence of a bulky phosphine ligand,
the anticipated square planar arrangement is less
distorted than in 4a, with bond angles including N1-
Pd-S1 of 90.95(9)° and S1-Pd-Cl2 of 176.33(4)°.
Bond Angles
C1-Pd1-N1
C1-Pd1-P1
N1-Pd1-P1
C1-Pd1-Cl1
N1-Pd1-Cl1
C31-P1-C21
C31-P1-Pd1
80.20(9)
94.81(7)
C11-P1-Pd1
C2-C1-Pd1
C7-N1-Pd1
C8-N1-Pd1
P1-Pd1-Cl1
C6-C1-Pd1
C21-P1-Pd1
111.12(8)
130.57(19)
115.76(16)
124.92(16)
92.19(3)
112.72(17)
118.48(9)
174.92(6)
171.84(7)
92.86(6)
100.53(12)
113.02(8)
In an attempt to form a palladacycle analogue by
C-H activation chemistry, 2d was reacted with Pd-
(OAc)2 in acetic acid followed by LiCl metathesis.
However, 1H NMR analysis of the crude reaction
mixture revealed the presence of more than one species
in solution. Hence, we concentrated our efforts on the
corresponding reaction of the cysteine-derived 1,4-
benzodiazepine 2e. Reaction of the latter with Pd(OAc)2
afforded the acetate analogue 6e, evidenced by the
presence of only eight aromatic protons, a singlet for a
single acetate group, and a downfield shift of 0.3 ppm
Figure 2. ORTEP diagram of 4a (hydrogen atoms omitted
for clarity).
palladacycles,5b,9a and the Pd-Cl bond length of 2.3602-
(7) Å reflects the high trans influence of the metalated
carbon atom.
(9) (a) Bedford, R. B.; Cazin, C. S. J.; Hursthouse, M. B.; Light, M.
E.; Pike, K. J.; Wimperis S. J. Organomet. Chem. 2001, 633, 173. (b)
Bedford, R. B.; Cazin, C. S. J.; Hursthouse, M. B.; Light, M. E.; Scordia,
V. J. M. J. Chem. Soc., Dalton Trans. 2004, 3864. (c) Louie, J.; Hartwig,
J. F. Angew. Chim. Int. Ed. 1996, 35, 2359. (d) Nowotny, M.; Hanefeld,
U.; van Koningsveld, H.; Maschmeyer, T. Chem. Commun. 2000, 1877.
(8) (a) Ebeling, G.; Meneghetti, M. R.; Rominger, F.; Dupont, J.
Organometallics 2000, 21, 3221. (b) Dupont, J.; Gruber, A. S.; Fonseca,
G. S.; Monteiro, A. L.; Ebeling, G.; Burrow, R. A. Organometallics 2001,
20, 171. (c) Spencer, J.; Pfeffer, M.; Kyritsakas, N.; Fischer, J.
Organometallics 1995, 14, 2214.

5668 Organometallics, Vol. 24, No. 23, 2005
Spencer et al.
partner) 4-bromoanisole, affording 4-methoxybiphenyl
in 90% yield (100% consumption of 4-bromoanisole,
entry 1, Table 3). Building on the promising activity of
3a we tested other derivatives for catalytic activity in
the same reaction, which is often used as a benchmark
for catalytic performance.1 Palladacycle 6f had a cata-
lytic performance similar to 3a (87% yield of 4-meth-
oxybiphenyl, entry 7), and the coordination complex 5d
had good activity (81% yield of 4-methoxybiphenyl, entry
5). The latter result is not surprising, as the related
10a
Pd(II) coordination complexes PdCl2(SEt2)2
Pd(OAc)2
and
10a-c
as well as other complexes,3f including
[Pd(NCOC2H4CO)(PPh3)2Br],10d are also effective pre-
catalysts for this type of transformation.
The reaction was also carried out over shorter reaction
times (2 h), and complex 6f was the most effective
precatalyst, with a high yield of 4-methoxybiphenyl
(92%) observed (entry 8). Attempts to use lower catalyst
loadings of 3a and 6f, over 27 h, led to moderate TONs,
1620 with 3a (entry 4) and 1440 with 6f (entry 9), which
are far inferior to many of the known palladacycle
systems.1,3
Figure 3. ORTEP diagram of 5d (hydrogen atoms, with
the exception of (H2), omitted for clarity).
Table 2. Selected Bond Lengths (Å) and Angles
(deg) for 5d
3a (0.5 mol % Pd) was tested in Suzuki coupling
reactions of aryl chlorides with phenylboronic acid under
the same conditions. Using the deactivated substrate,
4-chloroanisole, only a 4% yield of 4-methoxybiphenyl
was obtained, and with a more activated halide, 4-chlo-
roacetophenone, a modest conversion (56%) and yield
(34%) of 4-phenylacetophenone were observed. Chang-
ing the base (K2CO3, K3PO4, n-Bu4NBr) and/or solvent
(DMA, DMF, o-xylene) did not improve the coupling of
PhB(OH)2 with 4-chloroacetophenone. The use of a
phosphine as a co-ligand in palladacycle-mediated cou-
pling reactions has been described.4c,11 Hence, when we
combined PCy3 with 3a (0.5 mol % Pd) for the coupling
of PhB(OH)2 with 4-chloroacetophenone, quantitative
consumption of 4-chloroacetophenone was observed and
an 81% isolated yield of 4-phenylacetophenone was
found. Under identical conditions, with the deactivated
substrate, 4-chloroanisole, a 41% conversion of the
starting chloride was observed, along with a 38% yield
of 4-methoxybiphenyl (Scheme 7).
Bond Lengths
Pd1-N1
Pd1-Cl1
S1-C9
2.055(3)
2.3301(9)
1.815(4)
1.297(5)
Pd1-S1
Pd1-Cl2
S1-C10
N1-C2
2.2858(10)
2.3445(8)
1.820(5)
N1-C7
1.489(5)
Bond Angles
N1-Pd1-S1
N1-Pd1-Cl1
S1-Pd1-Cl1
N1-Pd1-Cl2
S1-Pd1-Cl2
Cl1-Pd1-Cl2
90.95(9)
177.77(9)
88.48(4)
89.24(9)
176.33(4)
91.47(3)
C9-S1-C10
C9-S1-Pd1
C10-S1-Pd1
C7-N1-C2
C7-N1-Pd1
C2-N1-Pd1
99.0(2)
103.73(15)
106.24(18)
116.7(3)
123.7(2)
119.1(2)
Scheme 5. Synthesis of the Palladacycles 6e and
6f
In line with our earlier studies, we have also probed
the catalytic activity of some of the above complexes in
the Heck reaction of various aryl halides and alkenes.12
The soluble and well-defined monomeric complex 4a was
selected and compared with the dimeric, less soluble,
phosphine-free precursors 3a and 3c.
As an initial point of comparison, the three selected
palladacycles were tested as precatalysts for the cou-
pling of olefins with the, less-reactive, electron-rich aryl
halides and in particular aryl bromides. As can be seen
from Table 4, good activity was observed, and as
expected, aryl iodides were more reactive than their
bromo congeners.4a,12 For example, a 97% yield of (E)-
butyl 3-p-tolylacrylate was observed with 4-iodotoluene
of the St-Bu group compared with 2e, attributed to an
S-Pd bond, in its 1H NMR spectrum.8 The chloro
analogue 6f was formed by a metathesis reaction with
excess LiCl in acetone.
Carbon-Carbon Bond Forming Reactions Me-
diated by 3-6. Palladacycles are well-established
precatalysts in Suzuki and Heck reactions, acting, after
activation, as a source of catalytically active Pd(0).1,3
As a preliminary assessment of the use of palladacycles
3, 4, and 6 in C-C bond forming reactions, we found
that the reaction of 3a with excess 3-tolylboronic acid
afforded the ortho-arylated benzodiazepine 7a as the
main product (Scheme 6).9
(10) (a) Gruber, A. S.; Pozebon, D.; Monteiro, A. L.; Dupont, J.
Tetrahedron Lett. 2001, 42, 7345. (b) Yao, Q.; Kinney, E. P.; Yang, Z.
J. Org. Chem. 2003, 68, 7528. (c) de Vries, A. H. M.; Mulders, J. M. C.
A.; Mommers, J. H. M.; Henderickx, H. J. W.; de Vries, J. G. Org. Lett.
2003, 5, 3285. (d) Fairlamb, I. J. S.; Kapdi, A. R.; Lynam, J. M.; Taylor,
R. J. K.; Whitwood, A. C. Tetrahedron 2004, 60, 5711.
(11) Bedford, R. B.; Cazin, C. S. J.; Hazelwood (ne´e Welsh), S. L.
Chem. Commun. 2002, 2608.
This result suggested that 3a could act as a source of
Pd(0), and accordingly, it was found to be an effective
precatalyst (0.5 mol % Pd) for the Suzuki coupling of
phenylboronic acid with the electron-rich (poor coupling
(12) Gruber, A. S.; Zim, D.; Ebeling, G.; Monteiro, A. L.; Dupont, J.
Org. Lett. 2000, 2, 1287.

Benzodiazepine-Based Palladium Complexes
Organometallics, Vol. 24, No. 23, 2005 5669
Scheme 6. Ortho-Functionalization of 3a
Table 3. Suzuki Coupling of 4-Bromoanisole and
PhB(OH)2 with Palladacycles 3a and 6f or
Complex 5d
Table 4. Heck Coupling Reactions of
Electron-Rich Aryl Halides and Olefins
entry 3 (mol % [Pd]) yielda (conversion)b reaction time (h)
conversionc
1
2
3
4
5
6
7
8
9
10
3a (0.5)
3a (0.5)
3a (0.2)
3a (0.05)
5d (0.5)
5d (0.5)
6f (0.5)
90 (100)
71 (94)
86 (100)
81 (100)
81 (100)
59 (74)
87 (98)
92 (100)
72 (92)
15 (43)
27
2
27
27
27
2
27
2
27
27
entrya [Pd]
ArX
R1
yield (%)b
(%)
1
3a
3c
4a
3a
3c
3a
3c
4a
3a
3a
3a
4-MeC6H4I
4-MeC6H4I
4-MeC6H4I
4-MeC6H4Br
4-MeC6H4Br
C6H4Br
CO2n-Bu 97 (84%)d
CO2n-Bu 91
CO2n-Bu 90
CO2n-Bu 74
CO2n-Bu 57
CO2n-Bu 96
CO2n-Bu 95
CO2n-Bu 78
98
91
95
75
63
96
95
78
88
89
91
2
3
4
5
6
6f (0.5)
7
C6H4Br
C6H4Br
6f (0.05)
6f (0.005)
8
9
4-MeOC6H4Br CO2n-Bu 70
a GC yield of 4-methoxybiphenyl (using undecane as an internal
standard). b GC conversion of 4-bromoanisole (using undecane as
an internal standard).
10
11
4-MeC6H4Br
C6H5Br
Ph
Ph
86
85
a Reaction conditions: 0.1 mol % [Pd], DMA (5 mL), NaOAc (1.4
mmol), alkene (1.2 mmol), ArX (1 mmol), and n-Bu4NBr (0.2
mmol), 120 °C, 24 h (time after which the reaction was analyzed).
b GC yield in (E)-butyl 3-arylacrylate or (E)-stilbenes (using un-
decane as an internal standard). c GC conversion. d Isolated yield.
Scheme 7. Suzuki Coupling of 4-Chloroarenes
with PhB(OH)2 Catalyzed by 3a
Table 5. Heck Coupling Reactions of
Electron-Poor Aryl Halides with n-Butyl Acrylate
as substrate, using 3a as precatalyst (entry 1, Table 4),
whereas with its bromo analogue a lower yield of
product (74%) was observed (entry 4). A similar trend
was observed when employing 3c as precatalyst, where
a 91% yield of coupled product was observed using
4-iodotoluene as aryl halide (entry 2) versus a 57% yield
with 4-bromotoluene (entry 5). The palladacycles 3c and
4a gave lower yields of coupling product than 3a; for
example, the yield of (E)-butyl 3-p-tolylacrylate was 91%
(3c, entry 2) and 90% (4a, entry 3) compared with 97%
(3a, entry 1), and this trend was repeated for the
formation of (E)-butyl cinnamate from bromobenzene
(compare entries 6-8). Gratifyingly, (E)-stilbene ana-
logues were formed in good yields from the coupling of
styrene with aryl bromides mediated by 3a (entries 10
and 11).
entrya [Pd]
ArX
yield (%)b conversion (%)c
1
3a
3c
4a
3a
3c
4a
3a
3c
4a
3a
3c
4a
3a
3a
4-MeCOC6H4Br 71
91
91
90
85
90
90
99
86
91
98
98
90
45
12
2
4-MeCOC6H4Br 89 (89%)d
4-MeCOC6H4Br 64
3
4
4-CNC6H4Br
4-CNC6H4Br
4-CNC6H4Br
4-NO2C6H4Br
4-NO2C6H4Br
4-NO2C6H4Br
4-CF3C6H4Br
4-CF3C6H4Br
4-CF3C6H4Br
4-MeCOC6H4Cl
4-MeCOC6H4Cl
70
82
90
96
83
70
98
94
69
31
8
5
6
7
8
9
10
11
12
13
14e
Electron-poor (activated) aryl bromides readily coupled
with n-butylacrylate in the presence of 3a, 3c, or 4a
(Table 5). The palladacycle 3c afforded better yields for
the coupling of n-butylacrylate with 4-acetobromoben-
zene (89%, entry 2) and 4-cyanobromobenzene (82%,
entry 5) than 3a (71%, entry 1, 70%, entry 4, respec-
tively). With the palladacycle 4a, for the coupling of
n-butylacrylate with 4-acetobromobenzene, a 64% yield
was observed (entry 3), whereas with 4-cyanobromoben-
zene, a 90% yield was observed (entry 6). In the case of
a Reaction conditions: 0.1 mol % [Pd], DMA (5 mL), NaOAc (1.4
mmol), alkene (1.2 mmol), ArX (1 mmol), and n-Bu4NBr (0.2
mmol), 120 °C, 24 h (time after which the reaction was analyzed).
b GC yield in (E)-butyl 3-arylacrylate or (E)-stilbenes (using
undecane as an internal standard). c GC conversion. d Isolated
yield. e At 150 °C.
4-nitrobromobenzene, yields of coupling product with
n-butylacrylate were higher with 3a (96%, entry 7) than
with 3c (83%, entry 8) or 4a (70%, entry 9). A similar

5670 Organometallics, Vol. 24, No. 23, 2005
Spencer et al.
(CDCl3): δ 172.9, 171.6, 139.9, 139.3, 132.1, 131.7, 130.7, 130.1,
128.5, 127.6, 123.6, 121.7, 57.1. (C15H12N2O); m/z 237 (MH+,
100%). Alternatively, the method of Stafford et al. was used.6a
1-Methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one, 2a.6b
The product from the previous step (0.50 g, 2.12 mmol) was
stirred with sodium hydride (60% suspension in paraffin oil,
0.12 g, 3.00 mmol) in DMF (10 mL) for 0.5 h under Ar.
Thereafter, iodomethane (264 µL, 4.24 mmol) was added and
the reaction was monitored by TLC until complete. After
dilution with ethyl acetate (30 mL), the organic layer was
washed with brine (2 × 30 mL) and water (20 mL), dried
(MgSO4), filtered, and concentrated in vacuo. The product was
obtained as a solid after column chromatography (7:3 ethyl
acetate/pentane) (0.47 g, 48%). 1H NMR (CDCl3): δ 7.63-7.16
(9H, m), 4.83 (1H, d), 3.81 (1H, d), 3.41 (3H, s). 13C NMR
(CDCl3): δ 170.8, 170.5, 144.5, 139.2, 131.7, 130.9, 130.7, 129.9,
128.6, 124.1, 121.4, 57.4, 35.2 (C16H14N2O); m/z 251 (MH+,
100%).
1-Benzyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one, 2b.
This was made on a 0.5 mmol scale (0.163 g, 55%) according
to the method used for the synthesis of 2a except that benzyl
bromide was used instead of methyl iodide. 1H NMR (CDCl3):
δ 7.47-7.06 (14H, m), 5.63 (1H, d, J(HH) ) 15.3 Hz), 4.89 (1H,
d, J(HH) ) 10.2 Hz), 4.79 (1H, d, J(HH) )15.3 Hz), 3.90 (1H,
d, J(HH) ) 10.2 Hz). 13C NMR (CDCl3): δ 171.0, 169.8, 142.6,
139.2, 137.2, 131.6, 130.9, 130.7, 130.6, 129.9, 129.0, 128.5,
127.8, 127.6, 124.8, 122.7, 57.4, 50.0 (C22H18N2O); m/z 327
(MH+, 100%).
trend was observed for the coupling of n-butylacrylate
with 4-trifluoromethylbromobenzene (98%, 3a; 94%, 3b;
69%, 4a, respectively, entries 10-12). As with the
Suzuki coupling reactions (Table 3), activated chlorides
were poor coupling partners and yields were worse at
elevated temperatures (entries 13 and 14, Table 5). In
a few cases isolated yields were obtained and were in
agreement with those determined by GC (entry 1, Table
4, and entry 2, Table 5).
Conclusion
We have demonstrated that the 1,4-benzodiazepine
system is a modular and versatile ligand for the
preparation of palladium complexes. Air-stable palla-
dacycles 3a-c and the “SCN pincer”13 palladacycle 6f
were prepared by C-H activation reactions, and the
reaction of 3a-c with PPh3 led to the monomeric 4a-
c. The novel monomeric coordination complex 5d was
formed from the reaction of 2d with Na2PdCl4 or PdCl2-
(MeCN)2.14 Complexes 3a and 6f displayed moderate
activity in Suzuki coupling reactions, whereas 3a, 3c,
and 4a had moderate activity in Heck couplings, which
may be due to poor catalyst longevity.3b Future studies
will be aimed at preparing 1,4-benzodiazepine-contain-
ing complexes to address this issue.
Benzyl 2-(2,3-dihydro-2-oxo-5-phenyl-1,4-benzodiazepin-
1-yl)acetate, 2c. This was made on a 1.9 mmol scale (0.364
g, 50%) according to the method used for the synthesis of 2a
except that benzyl bromoacetate was used instead of methyl
Experimental Section
General Procedures. All procedures were carried out in
air using commercial high-grade solvents (Fluka & Aldrich
Sureseal). Palladium salts were purchased from Aldrich and
used without further purification. Amino acids and coupling
1
iodide. H NMR (CDCl3): δ 7.61-7.20 (14H, m), 5.28 (2H, s),
4.85 (1H, d), 4.69 (1H, d), 4.53 (1H, d), 3.88 (1H, d). 13C NMR
(CDCl3): δ 171.0, 170.0, 169.2, 143.1, 135.6, 132.0, 131.0, 130.8,
130.0, 129.7, 128.9, 128.8, 128.6, 124.9, 121.5, 67.6, 56.8, 49.9
(C24H20N2O3); m/z 385 (MH+, 20%).
1
agents were purchased from Novabiochem. H, 13C{1H}, and
31P{1H} NMR spectra were recorded on a Bruker AC 300
spectrometer at 300, 75, and 120 MHz, respectively. Mass
spectra were carried out on a Waters ZQ spectrometer. Optical
activity measurements were recorded with a sodium lamp at
589 nM at 20 °C on an Optical Activity A10 polarimeter.
Elemental analyses were carried out by the Cambridge
University Microanalysis Service. Flash chromatography was
carried out on silica gel (Merck silica 60 (0.040-0.064 mm
grade)). Catalytic test reactions were performed as described
previously.12,15
3-(S)-(2-(Methylthio)ethyl)-5-phenyl-1H-1,4-benzodi-
azepin-2(3H)-one, 1d. 1d was made on a 6 mmol scale
according to the method used for 1a (0.99 g, 54%) except that
(L)-FMOC-Met-OH was used instead of FMOC-Gly-OH. 1H
NMR (CDCl3): δ 8.05 (1H, s), 7.53 (3H, m), 7.42 (4H, m), 7.15
(2H, m), 3.81 (1H, dd, J(HH) ) 5.4 Hz), 2.84 (1H, m), 2.53
(2H, m), 2.13 (3H, s).
3-(S)-1-Methyl-3-(2-(methylthio)ethyl)-5-phenyl-1H-1,4-
benzodiazepin-2(3H)-one, 2d. 1d was treated with sodium
hydride followed by iodomethane, on a 0.62 mmol scale, as for
the synthesis of 2b. The product was obtained as an oil (0.17
g, 85%) after flash chromatography (3:1 dichloromethane/ethyl
acetate): RD293 (+93.8°, CH2Cl2, c 1). 1H NMR (CDCl3): δ 7.61-
7.29 (8H, m), 7.17 (1H, m), 3.76 (1H, m), 3.40 (3H, s), 2.76-
2.43 (4H, m), 2.06 (3H, s). 13C NMR (CDCl3): δ 169.5, 167.6,
142.6, 137.7, 130.4, 129.3, 129.2, 128.6, 128.1, 127.2, 122.8,
120.2, 60.8, 34.1, 30.1, 29.7, 14.5 (C19H20N2OS); m/z 325 (MH+,
100%).
Synthesis. 5-Phenyl-1H-1,4-benzodiazepin-2(3H)-one,
1a. 2-Aminobenzophenone (1.18 g, 6.00 mmol), EEDQ (1.48
g, 6.00 mmol), and FMOC-Gly-OH (1.78 g, 6.00 mmol) were
combined in anhydrous THF (25 mL) and left to stir at room
temperature overnight. After dilution with ethyl acetate (40
mL) and successive washings with potassium hydrogen sulfate
solution (10%, 20 mL), saturated sodium hydrogen carbonate
(20 mL), and brine, the organic layer was dried (MgSO4),
filtered, and concentrated. The crude product was treated with
a 20% solution of diethylamine in acetonitrile (30 mL) at room
temperature for 2 h. After evaporation of the volatiles followed
by flash chromatography (70:30 ethyl acetate/hexane) an oil
3-(S)-(tert-Butylthio)methyl)-5-phenyl-1H-1,4-benzodi-
azepin-2(3H)-one, 1e. 1e was made on a 5.4 mmol scale
according to the method used for 1a (1.0 g, 60%) except that
(L)-FMOC-Cys(t-Bu)-OH was used instead of FMOC-Gly-OH.
1H NMR (CDCl3): δ 10.36 (1H, s), 7.53-7.00 (9H, m), 3.72 (1H,
t, J(HH) ) 6.6 Hz), 3.43 (2H, m), 1.34 (9H, s).
1
was obtained (0.99 g, 70%). H NMR (CDCl3): δ 8.65 (1H, s),
7.56-7.35 (7H, m), 7.19 (2H, m), 4.34 (2H, s). 13C NMR
3-(S)-(tert-Butylthio)methyl)-1-methyl-5-phenyl-1H-
1,4-benzodiazepin-2(3H)-one, 2e. 2e was made from 1e on
a 2.96 mmol scale according to the method used for 2a (0.40
g, 40%): RD293 (+93.0°, CH2Cl2, c 1). 1H NMR (CDCl3): δ 7.53-
7.02 (9H, m), 3.61 (1H, t, J(HH) ) 5.1 Hz), 3.33 (2H, m), 3.29
(3H, s), 1.23 (9H, s). 13C NMR (CDCl3): δ 170.3, 168.8, 144.0,
139.0, 131.8, 130.7, 130.1, 129.5, 128.6, 124.2, 121.7, 64.8, 42.7,
35.5, 31.4 (C21H24N2OS); m/z 353 (MH+, 25%).
(13) (a) Holton, R. A.; Nelson, R. V. J. Organomet. Chem. 1980, 201,
C35. (b) Ebeling, G.; Meneghetti, M. R.; Rominger, F.; Dupont, J.
Organometallics 2002, 21, 3221. (c) Dangel, B. D.; Godula, K.; Youn,
S. W.; Sezen, B.; Sames, D. J. Am. Chem. Soc. 2002, 124, 11856.
(14) For the formation of coordination complexes rather than
palladacycles when employing Na2PdCl4 as metallating agent, see (a)
Dunina, V. V.; Gorunova, O.; Kuz’mina, L. G.; Livantsov, M. V.;
Grishin, Y. K. Tetrahedron: Asymmetry 1999, 10, 3951. (b) Zhao, Y.;
Helliwell, M.; Joule, J. A. Arkivoc 2000, 1, 360.
(15) (a) Rosa, G. R.; Ebeling, G.; Dupont, J.; Monteiro, A. L. Synthesis
2003, 18, 2894. (b) Zim, D.; Gruber, A. S.; Ebeling, G.; Dupont, J.;
Monteiro, A. L. Org. Lett. 2000, 2, 2881.
Palladacycles [(L)PdCl]2 3a-c. Typically the ligand
2a-c was stirred with 0.9 equiv of Na2PdCl4 in EtOH (20 mL)

Benzodiazepine-Based Palladium Complexes
Organometallics, Vol. 24, No. 23, 2005 5671
Table 6. Crystal Data and Structure Refinement
for 4a
Table 7. Crystal Data and Structure Refinement
for 5d
empirical formula
fw
C
34H28ClN2OPPd
empirical formula
fw
C19H20Cl2N2OPdS‚CHCl3
653.40
621.10
cryst syst
space group
Z
tetragonal
P42/n
8
cryst syst
space group
Z
orthorhombic
Pbca
8
unit cell dimens
a ) 25.6119(4) Å
b ) 25.6119(4) Å
c ) 9.6401(2) Å
6323.61(19) Å3
1.37 g/cm3
R ) 90°
â ) 90°
γ ) 90°
unit cell dimens
a ) 12.4292(2) Å
b ) 15.3175(3) Å
c ) 25.2577(5) Å
4808.67(15) Å3
1.72 g/cm3
R ) 90°
â ) 90°
γ ) 90°
volume
density (calcd)
absorp coeff
max. and min. transmn
cryst shape
cryst size
cryst color
θ range for data collection
index ranges
volume
density (calcd)
absorp coeff
max. and min. transmn
cryst shape
0.75 mm-1
1.43 mm-1
0.93 and 0.77
polyhedron
0.92 and 0.61
polyhedron
0.38 × 0.37 × 0.06 mm3
orange
0.36 × 0.10 × 0.10 mm3
cryst size
cryst color
θ range for data collection 2.3 to 27.5°
index ranges
yellow
1.1 to 27.5°
-33 e h e 33,
-33 e k e 32,
-12 e l e 12
64 421
-16 e h e 16,
-19 e k e 19,
-32 e l e 32
47 344
5500 (R(int) ) 0.0332)
4619 (I > 2σ(I))
5500/0/277
no. of reflns collected
no. of indep reflns
no. of obsd reflns
no. of reflns collected
no. of indep reflns
no. of obsd reflns
7274 (R(int) ) 0.0437)
5776 (I > 2σ(I))
no. of data/restraints/params 7274/0/362
no. of data/restraints/
params
goodness-of-fit on F2
1.11
final R indices (I > 2σ(I))
largest diff peak and hole
R1 ) 0.030, wR2 ) 0.081
goodness-of-fit on F2
final R indices (I > 2σ(I))
1.04
0.79 and -0.56 e Å-3
R1 ) 0.040, wR2 ) 0.114
largest diff peak and hole 1.90 and -1.08 e Å-3
for 48 h at room temperature. The precipitate was isolated by
filtration, washed with further EtOH and then chloroform (10
mL each), and dried in vacuo. The complexes 3a-c were
obtained in 70% yield and were too insoluble for NMR
determinations.
7.17 (2H, m), 6.99 (2H, m), 4.27 (1H, d, J(HH) ) 6.6 Hz), 3.38
(4H, m), 3.00 (1H, m), 2.05 (3H, brs), 1.51 (9H, s). Anal. Calcd
for C23H26N2O3PdS: C, 53.44; H, 5.07; N, 5.42. Found: C,
53.04; H, 5.06; N, 5.23.
3a: Anal. Calcd for (C16H13ClN2OPd)2‚CHCl3: C, 43.96; H,
3.02; N, 6.21. Found: C, 44.16; H, 3.12; N, 6.26. 3b: Anal.
Calcd for (C22H17ClN2OPd)2‚0.5CHCl3: C, 51.28; H, 3.30; N,
5.30. Found: C, 51.21; H, 3.30; N, 5.30. 3c: Anal. Calcd for
(C24H19ClN2O3Pd)2: C, 54.88; H, 3.65; N, 5.35. Found: C, 54.30;
H, 3.61; N, 5.28 (too insoluble for purification).
Reaction of 3a-c with Triphenylphosphine. Equimolar
quantities of PPh3 and 3 were stirred in dichloromethane (10
mL) overnight. After filtration through Celite, the filtrate was
concentrated in vacuo and hexane added to afford a precipitate.
The latter was collected by filtration and dried in vacuo.
4a: 1H NMR (CDCl3): δ 7.72-7.27 (19H, m), 7.09 (1H, m),
6.85 (1H, m), 6.58 (2H, m), 6.12 (1H, d, J(HH) ) 12.3 Hz),
3.75 (1H, d, J(HH) ) 12.3 Hz), 3.41 (3H, s). 31P (CDCl3): δ 41
(s).
Palladacycle 6f. 6e (0.15 g, 0.29 mmol) was stirred with
LiCl (0.085 g, 2.00 mmol) in acetone for 30 min. After
evaporation of the volatiles, the resulting solid was extracted
with dichloromethane (3 × 20 mL) and filtered over Celite.
The filter cake was washed with acetone (30 mL), and the
combined filtrates were concentrated in vacuo to one-tenth
their volume. A beige solid was obtained by the addition of
hexane, collected by filtration, and dried in vacuo (0.144 g,
293
94%): RD (+488.2°, CH2Cl2, c 0.5). Anal. Calcd for C21H23-
ClN2OPdS‚0.5acetone: C, 51.73; H, 5.02; N, 5.36. Found: C,
51.61; H, 4.74; N, 5.63. 1H NMR (CDCl3): δ 7.99 (1H, d, J(HH)
) 7.8 Hz), 7.73 (2H, m), 7.40 (2H, m), 7.23 (1H, t, J(HH) ) 8.0
Hz), 7.05 (1H, m), 6.99 (1H, m), 4.39 (1H, d, J(HH) ) 6.3 Hz),
3.44 (1H, m), 3.43 (3H, s), 3.02 (1H, dd, J(HH) ) 6.3 Hz, J(HH)
) 5.1 Hz), 1.62 (9H, s). 13C NMR (CDCl3): δ 179.7, 168.6, 160.5,
143.0, 135.5, 133.4, 132.5, 130.6, 130.2, 125.8, 125.7, 124.9,
122.9, 64.0, 49.8, 36.1, 33.2, 30.2. 13C DEPT 135 NMR
(CDCl3): δ 135.5, 133.4, 132.5, 130.6, 130.2, 125.8, 124.9, 122.9,
64.0, 36.1, 30.2 (all CH), 33.2 (CH2).
4b: 1H NMR (CDCl3): δ 7.83-7.40 (19H, m), 7.07 (5H, m),
6.92 (2H, m), 6.56 (2H, m), 6.18 (1H, dd, J(HH) ) 15.3 Hz,
J(HH) ) 3 Hz), 5.38 (1H, d, J(HH) ) 12.0 Hz), 4.95 (1H, d,
J(HH) ) 15.3 Hz), 3.90 (1H, dd). 31P (CDCl3): δ 41 (s).
4c: 1H NMR (CDCl3): δ 7.83-7.32 (24H, m), 7.07 (1H, m),
6.85 (1H, m), 6.58 (2H, m), 6.18 (1H, dd, J(HH) ) 12.3 Hz),
5.17 (2H, dd, J(HH) ) 12.3 Hz), 4.73 (1H, d, J(HH) ) 15.3
Hz), 4.42 (1H, d, J(HH) ) 15.3 Hz), 3.86 (1H, d, J(HH) ) 12.3
Hz). 31P (CDCl3): δ 41 (s).
Coordination Complex [(LH)PdCl2] 5d. This complex
was made (0.080 g, 32%) by the method employed for 3, using
ligand 2d (0.17 g, 0.53 mmol) and Na2PdCl4 (0.147 g, 0.5
mmol): RD293 (+52.0°, CH2Cl2, c 1). Anal. Calcd for C19H20Cl2N2-
OPdS.CHCl3: C, 38.67; H, 3.41; N, 4.51. Found: C, 38.97; H,
3.60; N, 4.54. 1H NMR (300 MHz, CDCl3): δ 8.65 (5H, m), 7.45
(1H, d, J(HH) ) 8.4 Hz), 7.19 (3H, m), 3.97 (1H, m), 3.54 (1H,
m), 3.49 (3H, s), 2.76-2.39 (5H, m), 2.61 (1H, m).
Palladacycle 6e. 2e (0.12 g, 0.34 mmol) and palladium
acetate (0.070 g, 0.31 mmol) were stirred in acetic acid at 90
°C for 1 h. After cooling, the reaction mixture was filtered over
Celite, then concentrated in vacuo. The resulting oil was
washed with hexane and dried in vacuo. 6e was obtained as a
beige solid after crystallization from dichloromethane/hexane
(0.15 g, 94%). 1H NMR (CDCl3): δ 7.69 (2H, m), 7.38 (2H, m),
1-Methyl-5-(2-(3-tolyl)phenyl)-1H-1,4-benzodiazepin-
2(3H)-one, 7a. A toluene (15 mL) mixture of 3a (0.10 g, 0.25
mmol), 3-tolylboronic acid (0.17 g, 1.25 mmol), and potassium
carbonate (0.25 g, 1.81 mmol) was stirred under Ar at 110 °C
for 18 h. After cooling, the resulting black mixture was filtered
over Celite and the fitrate was concentrated in vacuo. The
residue was taken up in ethyl acetate (10 mL), washed with
brine, and dried (MgSO4). Filtration and evaporation of the
solvent gave the crude product, which after flash chromatog-
raphy (5:1 hexane/dichloromethane to 3:1 dichloromethane/
ethyl acetate) afforded an oil of limited purity (0.028 g, purity
1
1
ca. 80% by H NMR). H NMR (CDCl3): δ 7.49 (1H, m), 7.46
(2H, m), 7.23 (2H, m), 6.90 (5H, m), 6.70 (2H, m), 4.80 (1H, d,
J(HH) ) 8.4 Hz), 3.68 (1H, d, J(HH) ) 10.2 Hz), 3.10 (3H, s),
2.17 (3H, s) (C23H20N2O); m/z 341 (MH+, 100%).
X-ray Structure Determination. Data were collected on
a Bruker Smart CCD diffractometer at 200 K. Mo KR radiation
was used, and the intensities were corrected for Lorentz and
polarization effects. An empirical absorption correction was
applied using SADABS16 based on the Laue symmetry of the

5672 Organometallics, Vol. 24, No. 23, 2005
Spencer et al.
reciprocal space. Relevant crystal and data collection param-
eters are given in Tables 6 and 7. The structures were solved
by direct methods and refined against F2 with a full matrix
least-squares algorithm by using the SHELXTL software
package.16 Unless otherwise noted, hydrogen atoms were
considered at calculated positions and refined using appropri-
ate riding models. CCDC 281941 (5d) and 281942 (4a)
contain the supplementary crystallographic data for the
structures. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC,
12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223
336033; e-mail: deposit@ccdc.cam.ac.uk).
Acknowledgment. We thank CNPq for partial
financial support and for scholarships (M.P.S. and
V.I.R.).
Supporting Information Available: Tables of full crystal
data, atomic coordinates, calculated hydrogen coordinates,
anisotropic thermal parameters, and a complete list of bond
lengths and angles are available free of charge via the Internet
at http:/pubs.acs.org.
(16) Sheldrick, G. M. SHELXTL; Bruker Analytical X-ray-Divi-
sion: Madison, WI.
OM0506623