Metal complexes of biologically important ligands, Part CXVIII. Metathesis of dehydro amino acids with Fischer carbene complexes: Synthesis of complexes of amino acid- and peptide-α-carbenes and of isoindoles

Article abstract of DOI:10.1016/S0022-328X(99)00296-X

Metathesis of N-protected dehydro alanine esters with Fischer carbene complexes affords α-amino acid metal carbenes O(CH₂CH₂)₂N-C[=M(CO)₅](CO ₂Me) (3) and Ph₂C=N-C[=M(CO)₅](CO

Full text of DOI:10.1016/S0022-328X(99)00296-X

www.elsevier.nl/locate/jorganchem
Journal of Organometallic Chemistry 589 (1999) 21–28
Metal complexes of biologically important ligands, Part CXVIII.
Metathesis of dehydro amino acids with Fischer carbene
complexes: synthesis of complexes of amino acid- and
peptide-a-carbenes and of isoindolesꢀ
Harald Dialer, Kurt Polborn 1, Wolfgang Beck *
Institut fu¨r Anorganische Chemie der Ludwig-Maximilians-Uni6ersita¨t Mu¨nchen, Butenandtstraße 5-13, 81377 Munich, Germany
Received 31 March 1999
Dedicated to Professor Wolf Peter Fehlhammer on the occasion of his 60th birthday as a mark of friendship.
Abstract
Metathesis of N-protected dehydro alanine esters with Fischer carbene complexes affords a-amino acid metal carbenes
O(CH2CH2)2NꢀC[ꢁM(CO)5](CO2Me) (3) and Ph2CꢁNꢀC[ꢁM(CO)5](CO2Et) (6) (M=Cr, Mo, W). The X-ray structural analysis
of 6c shows the dominance of the zwitterionic form Ph2CꢁNꢁC[M(CO)5](CO2Et) in these complexes. Labeling of peptides by the
M(CO)5 fragment is demonstrated by the synthesis of Ph2CꢁNꢀC[ꢁCr(CO)5]CONHCH(CH2Ph)CO2Me (9). The strongly
fluorescent isoindole 7 was obtained from the carbene complexes 6 and was characterized by X-ray diffraction. © 1999 Elsevier
Science S.A. All rights reserved.
Keywords: Carbene; Amino acid; Peptide; Isoindole; Group 16 metals
1. Introduction
The application of amino acid carbenes could open
the access to new types of compounds and natural
products. Only recently one example of this type of
compound having a dimethylamino- and a carboxyl-
function directly attached to the carbene carbon atom
was published [9]. The method used [10] for generating
these metal carbenes via a tertiary amide of oxalic acid
and a carbonylmetallate is not suited for naturally
occurring amino acids and peptides due to the nucleo-
philicity and the basicity of the carbonylmetallate.
Since the classical Fischer route is not suited for the
synthesis of a-carbenes of amino acids, our approach
was based on an alkene metathesis [8,11] of derivatives
of a,b-didehydro amino acids with classic Fischer metal
carbenes.
Didehydro amino acids [12] are found in a number of
biologically active peptides, e.g. in antibiotics [13],
atrimycin [14], cirratiomycin [15] or in the celenamides
A–C [16]. The CꢁC double bond leads to a modifica-
tion in the peptide backbone due to the sp2-hybridiza-
tion of the a-carbon and can further be subject to
addition of amines or thiols.
The broad scope of the chemistry and application of
organometallic complexes of transition metals with a-
amino acids and peptides was recently reviewed [2].
Various a-metallated amino acids [3] may be useful for
the labeling of peptides [4] and are models for interme-
diates in the asymmetric hydrogenation of dehydro
amino acids [5].
Fischer metal carbenes are widely used reagents in
organic synthesis [6]. In the field of bioorganometallic
chemistry, the synthesis of amino acids starting from
amino carbene complexes [7] and the synthesis of car-
bohydrate-modified Fischer metal carbenes [8] are im-
portant examples. Metalla dehydro amino acids,
bearing a double bond between the a-carbon of the
amino acid and a metal, would represent amino acid
carbenes of Fischer type.
ꢀ For Part CXVII, see Ref. [1].
* Corresponding author.
1 X-ray structure determination.
0022-328X/99/$ - see front matter © 1999 Elsevier Science S.A. All rights reserved.
PII: S0022-328X(99)00296-X

22
H. Dialer et al. / Journal of Organometallic Chemistry 589 (1999) 21–28
Schiff base-protected serine esters [19] or alternatively
2. Results and discussion
by Hofmann elimination from ethyl-N-(diphenyl-
methylene-3-trimethylammonioalaninate iodide [20]. In
an analogous procedure 5 and one equivalent of the
appropriate Fischer carbene 2a–c were reacted in
toluene or THF in a sealed tube to give the red to
yellow carbene complexes 6a–c together with variable
amounts (dependent on the reaction conditions) of the
isoindole 7 (Scheme 2).
As the substrate for metathesis we first applied the
dehydro amino acid 1, which is easily available from
morpholine and methyl pyruvate [17]. Heating 1 in a
sealed tube with one equivalent of the appropriate
Fischer carbene complexes 2a–c [18] in toluene or THF
leads to the formation of the metal carbenes 3a–c. The
yield is strongly dependent on the metal used (Scheme
1). In the case of the less reactive molybdenum and
tungsten carbenes, higher temperatures or longer reac-
tion times do not afford any increase in yield due to the
thermal instability of 1. In the 13C-NMR spectra the
carbene resonance of the chromium complex 3a ap-
pears at 258.7 ppm, which compares with that of the
dimethylamino derivative [9] mentioned above. The
13C-NMR shifts for molybdenum compound 3b and
tungsten compound 3c are 249.4 and 239.2 ppm, re-
spectively. These complexes represent the first amino
acid a-carbenes of molybdenum and tungsten. The
1H-NMR spectra of 3a–c show the nonequivalence of
the methylene signals of the morpholine moiety arising
from the mesomeric form NꢁC(CO2Me)ꢀM which is
isolobal to a peptide bond.
The 13C-NMR spectra of the carbene compounds
6a–c clearly exhibit the enhanced donor function of the
diphenylmethyleneamino group compared with an
amino group, resulting in a high-field shift of the car-
bene signal. The carbene 13C-NMR shift for the com-
plexes 6a–c ranges from 201.7 ppm (for the chromium
compound 6a) to 183.3 ppm for the tungsten complex
6c. Considering the proposed mechanism for the forma-
tion of the isoindole 7 (Scheme 3), this observation is
not surprising as the major mesomeric contribution can
be assigned to structure A.
The nitrile ylide structure A is in accordance with the
spectroscopic results and was proved by X-ray analysis
of the tungsten complex 6c (Fig. 1; Tables 1 and 2).
As shown in Fig. 1, the distance N(1)ꢀC(6) of 1.253
,
In the IR spectra the three intensive carbonyl absorp-
tions can be observed at about 2060, 1980 and 1926
cm−1 (in accordance with local C46 symmetry), along
A is even shorter than the double bond of the Schiff
,
base N(1)ꢀC(7) at 1.283 A, the angle C(6)ꢀN(1)ꢀC(7)
being 167.3°. The negative partial charge at the metal,
on the other hand, results in an elongated carbene bond
with weaker ester bands at 1711 cm−1
.
,
In the search for dehydro amino acids suited for
metathesis we also concentrated on Schiff base-pro-
tected dehydro amino acids. These compounds are used
for the synthesis of amino acids via nucleophilic attack
at the methylene carbon atom [19,20]. In addition they
occur in the form of N-(pyridoxylidene)dehydroalanine
in the biosynthesis of some amino acids e.g. of tryp-
tophane [21].
W(1)ꢀC(6) of 2.208 A. A high contribution of a zwitter-
ionic form was also found in amino carbene complexes
LnMꢀC(R)ꢁNR2 [22].
Carbene complexes 6a–c (and also 3a–c) exhibit a
very high stability even in air and in aqueous solution.
The ester function in these complexes can be cleaved to
give the free carboxylic acids [9], bearing the possibility
of a subsequent peptide synthesis. The formation of
isoindole 7 involves the cleavage of the metal carbene
bond to yield the free nitrile ylide B, ring closure (C)
N-(Diphenylmethylene)-a,b-dehydroalanine ethyl es-
ter 5 can be synthesized by b-elimination of water from
Scheme 1.

H. Dialer et al. / Journal of Organometallic Chemistry 589 (1999) 21–28
23
Scheme 2.
and finally a sigmatropic 1,3-H shift. Some nitrile ylides
generated from 2-azirines by irradiation are known to
give isoindoles [23]. Fig. 2 shows the ORTEP projection
of isoindole 7, while important bond lengths and angles
are gathered in Table 3. The yield of 7 can be increased
by longer reaction times and higher temperatures. An
almost quantitative synthesis of 7 can be performed by
oxidation of the carbene complexes 6a–c with
Na2PdCl4 in methanol. Interestingly, derivatives of
isoindole, usually synthesized by a multistep reaction
via ring contraction from 1,4-benzodiazepines [24], are
applied as appetite suppressants [25].
of peptides by the easily detected metal pentacarbonyl
fragment is clearly demonstrated by the synthesis of a
N-protected, Cr(CO)5-containing dipeptide Ph2CꢁNꢀC-
[ꢁCr(CO)5]CONHCH(CH2Ph)CO2CH3 and a straight-
forward synthesis of isoindoles from the carbene com-
plexes 6 is presented.
4. Experimental
THF and toluene were distilled from sodium ben-
zophenone ketyl under argon. Chromatographic purifi-
cation of the metal carbenes was performed under
argon on previously degassed silica gel 60, 230–400
mesh (Merck). Chromatographic solvents were distilled
and degassed by bubbling argon through them for 10
min prior to use. NMR measurements were recorded
on Jeol GSX 270 or Jeol EX 400 spectrometers. IR
analyses were obtained on a Nicolet 520 FT-IR spec-
trometer. Mass spectra were recorded on a Finnigan
MAT 90 spectrometer.
Pentacarbonyl [(methoxy) phenylcarbene] chromium-
(0), -molybdenum(0) and -tungsten(0) (2a–c) [18], dehy-
dro amino acids 1 [17] and 5 [19,20] and N-diphenyl-
methylene-L-seryl-L-phenylalanine methylester [26] were
prepared according to literature procedures.
The described metathesis can also be performed us-
ing dehydropeptides. Reaction of the unsaturated
dipeptide
8
(available from
L-seryl-L-phenylala-
ninemethylester) with the Fischer carbene 2a in toluene
at 80°C leads to the formation of the pentacarbonyl
chromium-labeled dipeptide 9 (Scheme 4).
In the 13C-NMR spectra, the carbene resonance of
the peptide complex 9 appears at 202.0 ppm, which is in
accordance with the 13C shift of the amino acid carbene
6a (201.7 ppm). The CO-carbon signals appear at 217.8
ppm for cis-CO and at 224.7 ppm for trans-CO, respec-
tively. In the IR spectra the CꢂO absorptions at 2061
and 1941 cm−1 dominate the spectra compared with
the amide and ester absorptions, which proves peptide
metal carbenes like 9 to be very well suited as biomark-
ers. In addition, the corresponding isoindole 10 (iden-
tified by its typical fluorescence and its FAB mass
spectrum (m/z=398)) is formed along with a red com-
pound not yet identified.
4.1. General procedure for the synthesis of complexes
3a–c
To a 0.1 M solution of the dehydro amino acid 1 in
the solvent indicated one equivalent of the appropriate
Fischer carbene 2a–c is added under argon, and the
solution is heated (temperature see Scheme 1) in an
ace® pressure tube until TLC (silica gel, 3:1 hexane–
ethyl acetate) shows the consumption of 1. The solvent
is removed at reduced pressure and the crude reaction
mixture chromatographed on silica gel with 3:1 hex-
3. Conclusions
Using metathesis reactions the pentacarbonyl metal
fragment (metal=Cr, Mo, W) can be attached to the
a-carbon atom of N-protected a-amino acids. Labeling

24
H. Dialer et al. / Journal of Organometallic Chemistry 589 (1999) 21–28
Scheme 3.
ane–ethyl acetate. Typically, the red first-eluted frac-
tion contains the starting metal carbene and a-
methoxystyrene 4, while the yellow second one contains
the amino acid carbenes 3a–c.
222.3 (CꢁOtrans), 249.4 (CꢁMo). IR (KBr cm−1): 2060.7
(s), 1990.7 (m), 1958.5 (vs), 1921.9 (vs) [w(CꢂO)], 1710.9
(m) [w(CꢁO)]. C12H11MoNO8 (393.16) Calc.: C 36.66, H
2.82, N 3.56; Found: C 36.40, H 3.60, N 3.89%.
4.1.1. Pentacarbonyl[(methoxycarbonyl)(morpholino)-
methylene]chromium(0) (3a)
4.1.3. Pentacarbonyl[(methoxycarbonyl)(morpholino)-
methylene]tungsten(0) (3c)
To 257 mg (1.50 mmol) of 1 in 15 ml of toluene 468
mg (1.50 mmol) of pentacarbonyl(methoxyphenyl-
methylene)chromium(0) (2a) are added and the mixture
is heated to 90°C under argon for 5 h. Column chro-
matography (3:1 hexane–ethyl acetate) yields 456 mg
(87%) of the carbene 3a, which was recrystallized from
hexane at −30°C (yellow needles).
To 257 mg (1.50 mmol) of 1 in 15 ml of THF 666 mg
(1.50
mmol)
of
pentacarbonyl(methoxyphenyl-
methylene)tungsten(0) 2c are added and the mixture is
heated to 80°C under argon for 18 h. Column chro-
matography (3:1 hexane–ethyl acetate) yields 354 mg
3
1H-NMR (CDCl3, 270 MHz): l=3.63 (t, 2H, J=
3
4.7 Hz, CH2
3H, OꢀCH
2H, 3J=4.8 Hz, CH2
(OꢀCH3), 58.7 (CH2), 59.0 (C
(C
6
), 3.78 (t, 2H, J=4.7 Hz, CH2
6
), 3.87 (s,
3
6
3), 4.00 (t, 2H, J=4.8 Hz, CH2
6
), 4.32 (t,
6
). 13C-NMR (CDCl3): l=52.0
6
6
6 H2), 67.4 (C6 H2), 67.6
6
H2), 170.0 (CꢁOester), 216.2 (CꢁOcis), 222.3 (CꢁOtrans),
258.7 (CꢁCr). IR (KBr cm−1): 2061.2 (s), 1988.9 (m),
1957.0 (vs), 1926.9 (vs) [w(CꢂO)], 1711.0 (m) [w(CꢁO)].
C12H11CrNO8 (349.22) Calc.: C 41.27, H 3.17, N 4.01;
Found: C 41.31, H 3.13, N 3.90%.
4.1.2. Pentacarbonyl[(methoxycarbonyl)(morpholino)-
methylene]molybdenum(0) (3b)
To 257 mg (1.50 mmol) of 1 in 15 ml of THF 534 mg
(1.50
mmol)
of
pentacarbonyl(methoxyphenyl-
methylene)molybdenum(0) 2b are added and the mix-
ture is heated to 66°C under argon for 4 h. Column
chromatography (3:1 hexane–ethyl acetate) yields 336
mg (57%) of the carbene 3b, which was recrystallized
from hexane at −30°C (yellow needles).
1H-NMR (CDCl3, 270 MHz): l=3.51 (s, br, 2H,
CH2
(s br, 2H, CH2
(CDCl3): l=51.9 (OꢀC
67.5 (CH2), 67.6 (CH2), 170.0 (CꢁOester), 216.1 (CꢁOcis),
6
), 3.68 (s, br, 2H, CH2
), 3.51 (s br, 2H, CH2
H3), 58.7 (CH2), 59.0 (C
6
), 3.79 (s, 3H, OꢀCH3
). 13C-NMR
H2),
6 ), 3.91
6
6
6
6
6
Fig. 1. ORTEP projection of the tungsten complex 6c with the atom
numbering scheme.
6
6

H. Dialer et al. / Journal of Organometallic Chemistry 589 (1999) 21–28
25
Table 1
4.2. General procedure for the synthesis of complexes
6a–c and isoindole 7
Crystallographic data for 6a and 7 a
6a
7
To a 0.1 M solution of the dehydro amino acid 5 in
the solvent indicated one equivalent of the appropriate
Fischer carbene 2a–c is added under argon, and the
solution is heated (for the corresponding temperature
see Scheme 2) in an ace® pressure tube until TLC (silica
gel, 3:1 hexane–ethyl acetate) shows the consumption
of 5. The solvent is removed at reduced pressure and
the crude reaction mixture is chromatographed on silica
gel with 4:1 hexane–ethyl acetate. The red, first eluted
fraction contains the starting carbene complex and
a-methoxystyrene, the orange, second one contains the
amino acid metal carbenes 6a–c followed by a strongly
fluorescent fraction, which contains the isoindole 7.
Molecular formula
Formula weight
C22H15NO7W
589.20
C17H15NO2
265.30
,
a (A)
9.8195(11)
22.021(5)
10.866(2)
90.00(2)
108.456(14)
90.00(2)
2228.7(7)
4
26.403(2)
7.281(3)
14.857(3)
90.00(2)
95.429(14)
90.00(2)
2843.4(12)
8
,
b (A)
,
c (A)
h (°)
i (°)
k (°)
3
,
V (A )
Z
Crystal system
Space group
Absorption coefficient v
Monoclinic
P21/n
5.225
Monoclinic
C2/c
0.081
(mm−1
)
Density z (g cm−3
Crystal size (mm)
Diffractometer
)
1.756
1.239
0.40×0.33×0.27 0.53×0.43×0.27
Enraf Nonius
CAD 4
Mo–Ka
Enraf Nonius
CAD 4
Mo–Ka
4.2.1. Pentacarbonyl[(ethoxycarbonyl)(N-diphenyl-
methylenamino)methylene]chromium(0) (6a)
Radiation
To 419 mg (1.50 mmol) of 5 in 15 ml of toluene 468
mg (1.50 mmol) of pentacarbonyl(methoxyphenyl-
methylene)chromium(0) 2a are added and the mixture
is heated to 80°C under argon for 5 h. Column chro-
matography (4:1 hexane–ethyl acetate) yields 336 mg
(49%) of the carbene 6a, which was recrystallized from
hexane at +4°C (red plates).
,
,
(u=0.71073 A)
293(2)
(u=0.71073 A)
293(2)
Temperature (K)
Scan range (°)
q Limits (°)
Reflections collected
Independent reflections
0.90+0.45 tgq
2.18–23.97
3712
0.69+0.51 tgq
2.75–23.96
2324
3492
2218
(Rint=0.0509)
Semi-empirical
from C-scans
1.000 and 0.6264 0.9991 and
0.9761
(Rint=0.0078)
Semi-empirical
from C-scans
Absorption correction
1H-NMR (CDCl3, 400 MHz): l=1.41 (t, 3H,
Max. and min. transmis-
sion
Refinement method
CH2CH3
Ph). 13C-NMR (CDCl3): l=14.3 (C
129.3 (Car), 129.4 (Car), 129.9 (Car), 132.1 (Car), 165.6
6
), 4.38 (q, 2H, OꢀCH2
6
), 7.52–7.66 (m, 10H,
Full-matrix least- Full-matrix least-
6
H3), 63.2 (CH2),
6
squares on F2
squares on F2
2218/0/183
1.135
Data/restraints/parameters 3492/0/281
(C6 =N), 201.7 (CꢁCr), n.o.(CꢁOester), 216.2 (CꢁOcis),
Goodness-of-fit on F2
1.143
223.2 (CꢁOtrans). IR (KBr cm−1): 2060.3 (s), 1983.1 (m),
1931.2 (vs) [w(CꢂO)], 1720.0 (m) [w(CꢁO)].
C22H15CrNO7 (457.36) Calc.: C 57.78, H 3.31, N 3.06;
Found: C 57.88, H 3.36, N 2.99%.
Final R indices (I\2|(I)) R1=0.0324,
wR2=0.0770
R1=0.0405,
wR2=0.0982
R1=0.0573,
wR2=0.1093
R indices (all data)
R1=0.0429,
wR2=0.0837
0.875 and
Largest difference peak
and hole
Computations IBM PC/
Digital-ALPHA
Refinement
0.118 and
−3
−3
,
,
−1.069 e A
−0.121 e A
SHELXS-86 [27]
SHELXS-86 [27]
Table 2
SHELXL-93 [28]
SHELXL-93 [28]
,
Selected bond lenghts (A) and bond angles (°) for 6a
a For supplementary material, see Section 5.
,
Bond lengths (A)
W(1)ꢀC(1)
W(1)ꢀC(4)
W(1)ꢀC(5)
W(1)ꢀC(2)
W(1)ꢀC(3)
W(1)ꢀC(6)
O(1)ꢀC(1)
2.017(7)
2.023(7)
2.036(7)
2.036(7)
2.050(7)
2.208(6)
1.120(8)
O(2)ꢀC(2)
O(3)ꢀC(3)
O(4)ꢀC(4)
O(5)ꢀC(5)
N(1)ꢀC(6)
N(1)ꢀC(7)
C(6)ꢀC(20)
1.135(8)
1.119(8)
1.153(8)
1.118(8)
1.253(7)
1.283(7)
1.507(8)
(49%) of the carbene 3c, which was recrystallized from
hexane at −30°C (yellow needles).
3
1H-NMR (CDCl3, 270 MHz): l=3.64 (t, 2H, J=
3
4.9 Hz, CH2
3H, OꢀCH3
2H, 3J=4.8 Hz, CH2
(OꢀCH3), 57.8 (CH2), 57.9 (C
(C
6
), 3.83 (t, 2H, J=4.9 Hz, CH2
6
), 3.91 (s,
3
6
), 4.00 (t, 2H, J=4.8 Hz, CH2
6
), 4.27 (t,
Bond angles (°)
C(1)ꢀW(1)ꢀC(4)
C(1)ꢀW(1)ꢀC(5)
C(1)ꢀW(1)ꢀC(2)
C(1)ꢀW(1)ꢀC(6)
C(1)ꢀW(1)ꢀC(3)
C(4)ꢀW(1)ꢀC(6)
C(5)ꢀW(1)ꢀC(6)
6
). 13C-NMR (CDCl3): l=52.1
92.0(3)
90.7(3)
89.2(3)
178.4(3)
89.7(3)
88.8(2)
87.9(3)
C(6)ꢀN(1)ꢀC(7)
O(1)ꢀC(1)ꢀW(1)
O(3)ꢀC(3)ꢀW(1)
N(1)ꢀC(6)ꢀC(20)
N(1)ꢀC(6)ꢀW(1)
C(20)ꢀC(6)ꢀW(1)
N(1)ꢀC(7)ꢀC(8)
167.3(6)
179.7(6)
176.8(7)
113.2(5)
125.4(4)
121.3(4)
119.1(5)
6
6
6 H2), 67.3 (C6 H2), 67.5
6
H2), 170.7 (CꢁOester), 196.9 (CꢁOcis), 202.2 (CꢁOtrans),
239.2 (CꢁCr). IR (KBr cm−1): 2069.7 (s), 1980.6 (m),
1926.1 (vs) [w(CꢂO)], 1713.8 (m) [w(CꢁO)].
C12H11NO8W (481.07) Calc.: C 29.96, H 2.30, N 2.91;
Found: C 29.96, H 2.33, N 2.89%.

26
H. Dialer et al. / Journal of Organometallic Chemistry 589 (1999) 21–28
Fig. 2. ORTEP projection of isoindole 7 with the atom numbering scheme.
4.2.4. 3-Phenylisoindole-1-carboxylicacid ethylester (7)
As an example the isolation of 7 is described for the
reaction yielding 6a. After chromatographic separation
(4:1 hexane–ethyl acetate) of 6a a strongly fluorescent
fraction is collected, which contains impure 7. A second
column chromatography with 7:3 chloroform–hexane
as eluent yields 92 mg (23%) of 7. Slow crystallization
from chloroform–hexane gives analytically pure light
yellow crystals of 7.
4.2.2. Pentacarbonyl[(ethoxycarbonyl)(N-diphenyl-
methylenamino)methylene]molybdenum(0) (6b)
To 419 mg (1.50 mmol) of 5 in 15 ml of THF 534 mg
(1.50 mmol) of pentacarbonyl(methoxyphenylmethyl-
ene)molybdenum(0) 2b are added and the mixture is
heated to 66°C under argon for 4 h. Column chro-
matography (4:1 hexane–ethyl acetate) yields 158 mg
(21%) of the carbene 6b, which was recrystallized twice
from hexane–benzene at −30°C (orange plates).
1H-NMR (CDCl3, 400 MHz): l=1.41 (t, 3H,
1H-NMR (CDCl3, 300 MHz): l=1.43 (t, 3H,
3
CH2CH3
6
), 4.39 (q, 2H, OꢀCH2
6
), 7.17 (t, 1H, J=7.5
CH2CH3
Ph). 13C-NMR (CDCl3): l=14.2 (C
129.2 (Car), 129.3 (Car), 129.8 (Car), 132.1 (Car), 165.5
(CꢁN), 197.4 (CꢁMo), n.o. (CꢁOester), 216.1 (CꢁOcis),
223.1 (CꢁOtrans). IR (CH2Cl2 cm−1): 2062.4 (s), 1940.0
(vs) [w(CꢂO)], 1721.0 (w) [w(CꢁO)].
6
), 4.38 (q, 2H, OꢀCH2
6
), 7.53–7.67 (m, 10H,
3
Hz, Har), 7.32 (t, 1H, J=7.5 Hz, Har), 7.40 (t, 1H,
6
H3), 63.1 (CH2),
6
3J=7.1 Hz, p-Harom.), 7.51 (t, 2H, 3J=7.8 Hz, m-
3
Harom.), 7.78 (d, 2H, J=7.8 Hz, o-Harom.), 7.95 (d, 1H,
6
3J=8.2 Hz, Har), 8.12 (d, 1H, J=8.2 Hz, Har), 11.15
3
(s, broad, 1H, NH). 13C-NMR (CDCl3): l=14.7
(C6 H3), 60.3 (C6 H2), 111.6 (Car), 120.8 (Car), 120.9 (Car),
C22H15MoNO7·C6H6 (579.41) Calc.: C 58.04, H 3.66, N
2.42; Found: C 57.56, H 3.52, N 2.79%.
122.9 (Car), 123.2 (Car), 125.8 (Car), 127.3 (Car), 128.0
(Car), 128.3 (Car), 129.0 (Car), 129.2 (Car), 131.5 (Car),
162.5 (CꢁOester). IR (CH2Cl2 cm−1): 3686.0 (m), 2944.0
4.2.3. Pentacarbonyl[(ethoxycarbonyl)(N-diphenyl-
methylenamino)methylene]tungsten(0) (6c)
To 419 mg (1.50 mmol) of 5 in 15 ml of THF 666 mg
Table 3
(1.50
mmol)
of
pentacarbonyl(methoxyphenyl-
,
Selected bond lenghts (A) and bond angles (°) for 7
methylene)tungsten(0) 2c are added and the mixture is
heated to 66°C under argon for 18 h. Column chro-
matography (4:1 hexane–ethyl acetate) yields 239 mg
(27%) of the carbene 6c, which was recrystallized from
hexane at +4°C (orange plates).
,
Bond lengths (A)
N(1)ꢀC(1)
N(1)ꢀC(8)
C(1)ꢀC(2)
C(1)ꢀC(9)
C(2)ꢀC(3)
C(2)ꢀC(7)
1.353(2)
1.371(2)
1.413(2)
1.465(2)
1.418(2)
1.423(2)
C(3)ꢀC(4)
C(4)ꢀC(5)
C(5)ꢀC(6)
C(6)ꢀC(7)
C(7)ꢀC(8)
C(8)ꢀC(15)
1.356(3)
1.407(3)
1.355(3)
1.417(2)
1.406(2)
1.436(2)
1H-NMR (CDCl3, 270 MHz): l=1.39 (t, 3H,
CH2CH3
6
), 4.38 (q, 2H, OꢀCH2
6
), 7.51–7.67 (m, 10H,
H3), 63.3 (CH2),
Ph). 13C-NMR (CDCl3): l=14.2 (C
6
6
Bond angles (°)
128.9 (Car), 129.4 (Car), 129.9 (Car), 132.2 (Car), 166.1
(CꢁN), 183.3 (CꢁW), n.o.(CꢁOester), 197.4 (CꢁOcis),
202.7 (CꢁOtrans). IR (KBr cm−1): 2066.8 (s), 1975.9 (m),
1925.4 (vs) [w(CꢂO)], 1720.3 (m) [w(CꢁO)].
C22H15NO7W (589.21) Calc.: C 44.85, H 2.57, N 2.38;
Found: C 44.76, H 2.52, N 2.32%.
C(1)ꢀN(1)ꢀC(8) 112.24(13)
N(1)ꢀC(1)ꢀC(2) 106.49(14)
N(1)ꢀC(1)ꢀC(9) 123.65(14)
C(2)ꢀC(1)ꢀC(9) 129.8(2)
C(1)ꢀC(2)ꢀC(3) 132.6(2)
C(1)ꢀC(2)ꢀC(7) 107.55(14)
C(3)ꢀC(2)ꢀC(7)
C(4)ꢀC(3)ꢀC(2)
C(3)ꢀC(4)ꢀC(5)
N(1)ꢀC(8)ꢀC(15)
C(7)ꢀC(8)ꢀC(15)
O(1)ꢀC(15)ꢀC(8)
119.8(2)
118.5(2)
121.6(2)
120.73(14)
132.6(2)
125.3(2)

H. Dialer et al. / Journal of Organometallic Chemistry 589 (1999) 21–28
27
Scheme 4.
4.4. Peptide chromium carbene (9)
(vs), 2401.2 (s), 1736.3 (m), 1718.1 (m), 1521.1 (s),
1466.7 (vs). MS (EI) m/z (%)=265.3 (100); MS (ESI)
m/z (%)=287.2 (100), 265.2 (24), 219.2 (10), 191.2 (20).
UV (CHCl3): umax=369.4 nm. C17H15NO2 (265.31)
Calc.: C 76.96, H 5.69, N 5.28; Found: C 76.34, H 5.75,
N 5.11%.
To 79 mg (0.19 mmol) of 8 in 15 ml of toluene 60 mg
(0.19 mmol) of pentacarbonyl(methoxyphenyl-
methylene)chromium(0) 2a are added and the mixture
is heated to 80°C under argon for 4 h. Repeated
column chromatography (3:1 hexane–ethyl acetate)
yields 26 mg (23%) of the carbene complex 9 (orange
powder).
Alternatively, 7 can be synthesized by stirring 100 mg
(0.22 mmol) of 6a and 65 mg (0.22 mmol) Na2PdCl4 in
7 ml of methanol for 1 h. The mixture is filtered on
Celite by suction to remove the precipitated palladium
and evaporated in vacuo. Column chromatography
with 7:3 chloroform–hexane as eluent yields 50 mg
1H-NMR (CD2Cl2, 300 MHz): l=3.35 (s, 3H,
OꢀCH3
1H, NH
(CD2Cl2): l=36.0 (C
6
), 3.72 (m, 2H, CH2
), 7.22–7.53 (m, 15H, Harom.). 13C-NMR
H2), 51.0 (OCH3), 60.0 (a-C),
6 ), 4.17 (m, 1H, a-H6 ), 6.78 (d,
6
6
6
6
1
(87%) of pure 7, identified by its H-NMR and mass
125.2 (C), 126.4 (C), 127.9 (C), 128.1 (C), 128.8 (C),
129.5 (C), 129.8 (C), 130.2 (C), 130.5 (C), 134.3 (C),
135.5 (C), 137.5 (C), 145.3 (C), 162.5 (CꢁN), 170.8
(CꢁOamide), 172.4 (CꢁOester), 202.0 (CꢁCr), 217.8
(CꢁOcis), 224.7 (CꢁOtrans). IR (CH2Cl2 cm−1): 2061.1
(s), 1941.3 (vs), 1751.1 (s), 1712.4 (vs). C30H22CrN2O8
(590.51). MS (FAB): m/z=591 [M+H+], 562 [M−
CO], 536 [M−2CO].
spectra.
4.3. N-Diphenylmethylene-h,i-didehydroalanyl-(
phenylalanine methylester (8)
L)-
To 160 mg (0.4 mmol) of N-diphenylmethylene-(
L)-
seryl-( )-phenylalanine methylester in 10 ml of dry
L
CH2Cl2, 124 ml (0.8 mmol) of 1,3-diisopropylcarbodi-
imide and 12 mg (0.4 mmol) of CuCl are added. The
mixture is stirred for 32 h at 40°C with exclusion of
moisture and light, filtered on Celite by suction, washed
with H2O (3×10 ml), dried (Na2SO4) and evaporated
in vacuo. Column chromatography (silica gel; 4:1 hex-
ane–ethyl acetate) is used to obtain 134 mg (81%) of
pure compound 8 as a foam.
5. Supplementary material
Crystallographic data (excluding structure factors)
for the structures reported in this paper have been
deposited with the Cambridge Crystallographic Data
Centre as supplementary publication nos. CCDC
118820 (6c) and CCDC 118819 (7). Copies of the data
can be obtained free of charge on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
[Fax: +44-1223-336033; e-mail: deposit@ccdc.cam.
ac.uk].
1H-NMR (CD2Cl2, 300 MHz): l=3.04 (m, 2H,
CH
(dd, 1H, a-H
6.91–7.59 (m, 15H, Harom.). 13C-NMR (CD2Cl2): l=
36.7 (CH2), 51.2 (OCH3), 60.1 (a-C), 104.3 (C), 125.6
6
2), 3.63 (s, 3H, OꢀCH3
6
), 4.12 (s, 1H, ꢁCH2
6
), 4.78
6
), 5.20 (s, 1H, ꢁCH2
6
), 6.85 (d, 1H, NH
6
),
6
6
6
(C), 126.0 (C), 127.3 (C), 127.4 (C), 127.6 (C), 127.9
(C), 128.2 (C), 128.4 (C), 130.3 (C), 134.1 (C), 135.2
(C), 137.6 (C), 147.2 (C), 165.6 (CꢁN), 169.4
(CꢁOamide), 170.8 (CꢁOester). IR (CH2Cl2 cm−1): 1746.0
(s), 1679.2 (vs), 1625.0 (s), 1598.1 (s), 1553.0 (vs).
C26H24N2O3 (412.48). MS (FAB): m/z=413 (68) [M+
H+], 435 (13) [M+Na+], 825 (55) [2M+H+].
Acknowledgements
We thank Deutsche Forschungsgemeinschaft, Fonds
der Chemischen Industrie and Wacker Chemie,
Mu¨nchen, for generous support and Professor W.

28
H. Dialer et al. / Journal of Organometallic Chemistry 589 (1999) 21–28
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