Reactivity of ferrocenylalkyl isocyanides. Formation of potential antibiotics and of gold(I) complexes

Article abstract of DOI:10.1016/S0022-328X(97)00468-3

Reactions of the ferrocenylalkyl isocyanides CNCH(R)Fc (Fc=Fe(η⁵-C₅H₅)(η⁵-C ₅H₄), R=cHex, tBu) with imines and carboxylic acids lead to derivatives of valine or of antibiotics (β-lactams and penicillins) containing the ferrocenyl group which could not be cleaved from the molecules under acidic conditions. The formation of the penicillin derivatives is stereoselective. The isocyanides CNCH(R)Fc (R=H, iPr, cHex) and CN(EtO₂C)C=CHFc react with [AuCl(PPh₃)] to give the corresponding gold(I) complexes [AuL(PPh₃)]A (L=ferrocenyl alkyl isocyanide, A=Cl or BPh₄ when the reaction is carried out in the presence of Na[BPh₄]). Cyclic voltammetry in aprotic medium shows that these complexes undergo a reversible single electron oxidation at the iron(II) site at a platinum electrode at a potential which is similar to that observed for the corresponding uncoordinated isocyanides.

Full text of DOI:10.1016/S0022-328X(97)00468-3

Ž
.
Journal of Organometallic Chemistry 552 1998 17–21
Reactivity of ferrocenylalkyl isocyanides. Formation of potential
ž /
antibiotics and of gold I complexes
a
a
b
Yu-Ying Tong , Joao J.R. Frausto da Silva , Armando J.L. Pombeiro a,), Gabriele Wagner ,
˜
´
b,1
Rudolf Herrmann
a
Centro de Quımica Estrutural, Complexo I, Instituto Superior Tecnico, AÕ. RoÕisco Pais, P-1096 Lisboa Codex, Portugal
Institut fur Organische Chemie und Biochemie der Technischen UniÕersitat Munchen, Lichtenbergstr. 4, Garching D-85747, Germany
´
´
b
¨
¨
¨
Received 16 May 1997
Abstract
5
5
Ž .
Ž
Ž
Ž
.Ž
.
.
.
Reactions of the ferrocenylalkyl isocyanides C[NCH R Fc FcsFe h -C5H5 h -C5H4 , RscHex, tBu with imines and
carboxylic acids lead to derivatives of valine or of antibiotics b-lactams and penicillins containing the ferrocenyl group which could not
be cleaved from the molecules under acidic conditions. The formation of the penicillin derivatives is stereoselective. The isocyanides
Ž .
Ž
Ž
.
Ž
.
w
Ž
.x
Ž .
C[NCH R Fc RsH, iPr, cHex and C[N EtO2C C5CHFc react with AuCl PPh3 to give the corresponding gold I complexes
w
Ž
.x
w
x.
AuL PPh3 A Lsferrocenyl alkyl isocyanide, AsCl or BPh4 when the reaction is carried out in the presence of Na BPh4 . Cyclic
Ž .
voltammetry in aprotic medium shows that these complexes undergo a reversible single electron oxidation at the iron II site at a platinum
electrode at a potential which is similar to that observed for the corresponding uncoordinated isocyanides. q 1998 Elsevier Science S.A.
Ž .
Keywords: Ferrocenylalkyl isocyanides; Gold I complexes; Electrochemistry; Four-component reactions; b-Lactams
1. Introduction
2. Results and discussion
The combination of ferrocene with an isocyanide
functional group in one molecule is of potential interest
for the construction of bimetallic compounds with the
possibility of electronic communication between the
two metal centres, since the isocyanide group is known
as a good ligand for transition metals. We have pre-
pared such compounds and tested their reactivity in the
(
2.1. Reactions with imines and carboxylic acids four-
component reactions
)
A typical organic reaction of isocyanides is the four-
component reaction, consisting in the combination of an
isocyanide, an amine, a carbonyl compound, and an
acid to form a single product possibly as a mixture of
diastereoisomers 3 . Interesting compounds thus ob-
tained are peptide derivatives 4,5 and antibiotics 6 .
The four-component reactions performed in this study
with ferrocenylalkyl isocyanides are shown in Fig. 1.
w x
formation of chromium carbonyl complexes 1 and
Ž
w x
studied their electrochemistry 2 . We found that reac-
.
w x
tions involving the isocyanide group performed well,
while reactions based on the formation of carbanions by
deprotonation of the position a to the isocyanide were
not successful. We now wish to report on the reactivity
of ferrocenylalkyl isocyanides in typical inorganic and
w
x
w x
Ž . Ž .
The products 1 – 3 have been fully characterised by
1H and 13C NMR spectroscopy, chromatography, and
Ž .
organic reactions, namely with a gold I phosphine cen-
Ž
.
elemental analysis see Section 4 .
In the reaction leading to the valine derivative 1 ,
tre or with imines and carboxylic acids, to form prod-
ucts with potential biological activity.
Ž .
the carbonyl compound 2-methylpropanal and the
Ž
.
Ž
.
amine benzylamine were precondensed to the imine
prior to treatment with the isocyanide and benzoic acid.
A mixture of two diastereoisomers each as a racemic
mixture in the ratio 1:1 was obtained, showing that the
stereogenic centre present in the ferrocene derivative
Ž
)
.
Corresponding author.
1 Also corresponding author.
0022-328Xr98r$19.00 q 1998 Elsevier Science S.A. All rights reserved.

(
)
18
Y.-Y. Tong et al.rJournal of Organometallic Chemistry 552 1998 17–21
Fig. 1.
( )
does not have sufficient chiral-inducing capability to
influence the stereochemistry at the newly-formed stere-
ogenic centre in the valine moiety of 1 . The total lack
2.2. Reactions with the gold I centre
Ž .
The isocyanide group is able to coordinate to a
variety of transition metal sites for reviews, see Refs.
9–11 , and we have reported previously the coordina-
tion to the chromium pentacarbonyl centre to form the
corresponding dinuclear complexes
Ž
of stereocontrol contrasts sharply with the well-known
w x
w
x.
high-inducing ability of ferrocenylalkylamines 7 . A
rationale for the difference is that the stereogenic centre
in an isocyanide does not come as close to the imine
carbon in the transition state and in the intermediates of
the reaction as the stereogenic centre in the amine does.
A better result, however, was obtained in the formation
w
Ž
.
CO 5 Cr
Ä
Ž .
4
x
Ž
.
w
x
CNCH R Fc RsH or organic substituent 1,2 . We
Ž .
w
Ž
.x
have now chosen the gold I centre of AuCl PPh3 as
Ž .
target since gold I phosphine complexes are known to
catalyse aldol type reactions of isocyanides with poten-
Ž .
of the b-lactam
2 from 2-methylpropanal and b-
w
x
alanine. Here, the diastereoisomers formed in a 3:1
ratio. In 2,5,5-trimethyl-2,5-dihydrothiazole-2-acetic
acid, finally, three of the four functional groups are
preorganised, and the stereogenic centre present in this
starting material should lead to four diastereomeric
tial industrial applications 12 . Such complexes are also
known to act as chemotherapeutic agents with antitumor
w
x
and antiarthritic activities 13 . For this purpose, we
Ž .
have already prepared a few gold I complexes with
w
Ž
bulky thiolates, in particular Au SC 6 H 2 R 3-
Ž . Ž .
3 each as racemic mixture .
.Ž
.
x
Ž
.
.
penicillin derivatives
2,4,6 PPh3 RsMe, iPr , either by addition of PPh3
w
Ž
x6
Interestingly, only two of them are formed. This selec-
tivity can be explained by the mechanism of the four-
component reaction which starts with a nucleophilic
attack of the carboxylate to the isocyanide group. This
enforces a cis-arrangement of the amido substituent
to Au SC 6 H 2 R 3-2,4,6
or by reaction of
AuCl PPh3 in THF with the appropriate thiol in the
w
Ž
.x
w
x
presence of KOHrEtOH 14 . Such thiolate complexes
and their crystal structure analysis have been obtained
w
x
earlier also by Schmidbaur et al. 15 by the reaction of
AuCl PPh3 with the corresponding thiols in the pres-
Ž
w
Ž
.x
formed by the reaction of this intermediate with the
.
protonated imine and the b-lactam ring. The configura-
ence of triethylamine.
tions of the two diastereoisomers are therefore
RF)c ,R),R) and RF)c ,S),S), where the subscript Fc
denotes the stereogenic centre in the position a to
ferrocene.
For practical applications, it would be necessary to
cleave the ferrocenylalkyl substituent from the potential
antibiotic under mild conditions. From the products of
four-component reactions with ferrocenylalkyl amines,
this can be achieved with trifluoroacetic acid which
leads to the formation of highly stable a-ferrocenylalkyl
In the present study, we have observed that refluxing
w
Ž
.x
a THF solution of AuCl PPh3 with CNCH2 Fc for
two days leads to the formation of the expected com-
w
Ž
.Ž
.
x
Ž .
plex Au CNCH2 Fc PPh3 Cl 4 . When the reaction
w
x
is carried out in the presence of Na BPh4 , heating is
n o t r e q u ir e d
a n d
th e
Ž
c o m p le x e s
w
Ä
Ž .
4
Ž
Ž
.
xw
x
Ž .
Au CNCH R Fc PPh3 BPh4 RsiPr 5 or cHex
Ž ..
w
Ä
.
4
Ž
.
xw
x
Ž .
6
and Au CN EtO2C C5CHFc PPh3 BPh4
7
are isolated from the reaction with the appropriate ferro-
cenyl isocyanide at room temperature.
w x
carbocations 8 . Surprisingly, this failed completely in
the case of the products 1 – 3 obtained from ferro-
These reactions involve the displacement of the chlo-
ride ligand by the isocyanide and lead to ionic species.
Ž . Ž .
w
x
cenylalkyl isocyanides. No reaction occurred. The only
obvious difference is that the ferrocenylalkyl moiety is
bound to a secondary nitrogen atom in the compounds
This is clearly different from the reported 16 formation
w
Ž
of neutral isocyanide complexes AuCl CNC6 H4 F-3 or
.
x
by displacement of dimethylsulfide from
-4
w
Ž . Ž .
Ž
.x
1 – 3 while it is bound to a tertiary nitrogen atom in
AuCl SMe2 by the isocyanide. As no further nucle-
ophiles are present in the reaction mixture, the iso-
cyanide complexes do not react further to form imino
derivatives, as was observed in the reaction of
the products from ferrocenylalkyl amines. This differ-
ence prevents the use of the ferrocenylalkyl isocyanides
as reagents for the synthesis of b-lactam antibiotics.

(
)
Y.-Y. Tong et al.rJournal of Organometallic Chemistry 552 1998 17–21
19
w
Ž
.x
AuCl PPh3
with aromatic isocyanides in
x
case, a fact which prevents the use of the ferroceny-
lalkyl isocyanides as auxiliaries for the synthesis of
antibiotics.
w
KOHrmethanol 17 . Here, chloride is displaced by the
isocyanide first, and the coordinated isocyanide is then
attacked nucleophilically by the methoxide ion to form,
The coordination ability of the isocyano group to-
wards a transition metal can be used for the preparation
of bimetallic complexes with potential use as
w
Ä
Ž
.
4
Ž
.x
e.g., Au C OMe 5NC6 H5 PPh3 .
Ž . Ž .
The complexes 5 – 7 were isolated as yellow solids
and characterised by IR, H NMR and 31 P NMR spec-
1
Ž .
chemotherapeutics, such as the gold I complexes de-
troscopy, cyclic voltammetry and elemental analysis.
Their IR spectra exhibit bands typical for triphenylphos-
phine and the n CN vibration of the isocyanide ligands
scribed here. Electronic effects of such a coordination
on the redox properties of the iron II site are not
Ž .
Ž
.
sufficiently intense to allow for a definite interpretation,
y1
Ž
Ž
.
the latter falling in the range of 2100–2180 cm
in
nor does the shift of the n CN vibration upon coordina-
tion. The attenuation of the electronic effects by satu-
rated carbon bridges between the two metal centres may
account for the lack of electronic communication be-
tween iron and gold.
.
Ž
.
KBr discs , whereas the strong n Au–Cl band at 325
cmy1 18,19 of the parent complex AuCl PPh3 is not
observed, confirming the replacement of chloride by the
w
x
w
Ž
.x
Ž
.
isocyanide ligand. The shift of the n CN vibration
upon coordination to the gold I centre is quite low
Ž .
y1
Ž
<
<
.
Dn F40 cm , indicating that only a modest activa-
tion of the isocyanide group can be expected. By cyclic
4. Experimental
w
xw
x
voltammetry in 0.2 M NBu4 BF4 in CH2Cl2 , THF or
acetonitrile, the ferrocenylalkyl isocyanide complexes
exhibit a single-electron reversible anodic wave at a
half-wave oxidation potential which is very close to that
4.1. General
The ferrocenylisocyanides were prepared as de-
w
x
Ž
<
<
.
w
x
w
Ž
.x
of the free ligands 1,2,20 D E1r2 F0.06 V . This
scribed 1,21 . AuCl PPh3 was obtained from
Ž .
Ž
.
w
x
w x
wave is assigned to the Fe II rFe III transition. There-
H AuCl4 by a published method 22 . The reactions
were carried out in the absence of air using standard
inert-gas flow and vacuum techniques. Solvents were
purified by standard procedures. NMR spectra were
fore, the coordination of the isocyano group to the
Ž .
gold I centre does not have an appreciable effect on the
energy of the HOMO as compared to the free ligand. A
similar behaviour was observed upon coordination of
recorded in CDCl3 with Bruker AM 360 and Varian
13
Unity 300 instruments. Internal SiMe4 1H and C and
external 85% H3PO4
Ž
.
w
x
Ž
.
ferrocenylalkyl isocyanides to the Cr CO centre 1,2 .
5
Ž31
.
The main reason for this observation is probably the
separation of the isocyanide from the ferrocene moiety
by a tetracoordinated carbon atom in 4 – 6 or two
P were used as standards; d
values are quoted. IR measurements were carried out
with a Perkin-Elmer 683 spectrophotometer. Microanal-
Ž . Ž .
Ž .
Ž
.
carbon atoms although unsaturated in 7 which leads
yses were performed at Centro de Quımica Estrutural,
´
to an attenuation of the electronic effects.
Lisboa, and Institut fur Organische Chemie der TU
¨
¨
Munchen, Garching. The electrochemical experiments
were performed on an EG&G PARC 173 potentiostat
and an EG&G PARC 175 universal programmer. A
two-compartment three-electrode cell, with a platinum-
wire working electrode, probed by a Luggin capillary
connected to a silver wire pseudoreference electrode
and a platinum auxiliary electrode, was employed. The
3. Conclusion
In this study, the potential of ferrocenylalkyl iso-
cyanides to the synthesis of compounds with pharma-
ceutical applications was explored. They undergo read-
ily four-component reactions to form peptide and antibi-
otic derivatives. The chiral inducing power of ferro-
cenylalkyl isocyanides with a stereogenic centre a to
the isocyanide group is, however, not very high, and
mixtures of diastereoisomers are always obtained. To
achieve stereoselectivity requires a suitable preorganiza-
tion of the other functional groups prior to reaction with
the isocyanide, as is the case with the dihydrothiazole
derivative which leads to only four of the expected eight
w
xw
x
potentials were measured in 0.2 M NBu4 BF4 in
CH2Cl2 , acetonitrile, or THF, using the trans-
0rq
w
Ž
.Ž .2 x
ReCl N2 Ph2 PCH2CH2 PPh2
redox couple
ox
Ž
.
E1r2 s0.28 V vs. SCE as internal reference.
4.2. Four-component reactions
( )
4.2.1. Compound 1
Ž
.
To a solution of N- 2-methylpropylidene benzyl-
Ž .
Ž
.
stereoisomers of the penicillin derivative 3 . From the
amine 10 mmol, 1.61 g in 35 ml of dry methanol was
Ž
.
experience with ferrocenylalkyl amines as chiral induc-
ing agents in four-component reactions, it was expected
that the ferrocenylalkyl group should be easily cleaved
from the reaction products under acidic conditions to
leave the active antibiotic. However, this was not the
added under nitrogen benzoic acid 10 mmol, 1.22 g
Ž
and 1-cyclohexyl-1-isocyano-methylferrocene 10
.
mmol, 3.05 g . The mixture was stirred for 20 h at room
temperature. Volatile components were stripped off in
vacuum, and the residue was treated with diethyl ether

(
)
20
Y.-Y. Tong et al.rJournal of Organometallic Chemistry 552 1998 17–21
Ž
.
Ž
Ž
.
..
Ž
200 ml . The ethereal solution was washed succes-
4.10 m, 5H, cp subst. qFc–C H , 4.68 d, 1H, Js
13
Ž
.
Ž
.
Ž
.
sively with water 50 ml , 2% aqueous tartaric acid 100
10.3 Hz, CO–C H–N . C NMR CDCl3, 90.55 MHz :
.
Ž
.
Ž
.
Ž
.
Ž
.
Ž
.
ml , 1 N aqueous NaOH 100 ml and water 50 ml .
After drying with Na2 SO4 and evaporation of the sol-
vent, the residue was recrystallised from hexane to give
a 1:1 mixture of diastereoisomers 4.10 g, 70% . They
could be separated by chromatography silica gel, hex-
19.4 Me2CH , 26.6 Me3C , 28.2 Me2CH , 35.9, 38.7
Ž
.
Ž
.
Ž
.
Ž
2=CH2 , 36.1 Me3C , 56.9 Fc–CH , 62.8 CO–
..
.
Ž
Ž
Ž
Ž
CH–N , 68.6 cp unsubst. , 65.7, 66.7, 67.4, 69.7 CH,
Ž
.
Ž
.
Ž
..
Ž
.
cp subst. , 87.8 Cq, cp subst. , 167.8, 168.0 C5O .
Found: C, 64.9; H, 7.79; N, 6.88%; C23 H32 FeN2O2
requires C, 65.09; H, 7.60; N, 6.60%.
Ž
.
anerethyl acetate 2:1 .
1
Ž
.
Ž
Isomer I Rf 0.60 , m.p. 1958C. H NMR CDCl3,
.
Ž
.
( )
360 MHz : 0.80–1.80 m, 11 H, cyclohexane , 1.08 and
4.2.3. Compound 3
2,5,5-Trimethyl-2,5-dihydrothiazole-2-acetic acid
1.87 g, 10 mmol and 1-isocyano-2,2-dimethyl-pro-
pylferrocene 2.81 g, 10 mmol were dissolved in 20 ml
of dry methanol and stirred for 24 h at room tempera-
ture. After removal of the solvent, the residue was
Ž
.
Ž
1.04 2=d, 3H each, Js6.4 Hz, Me2CH , 2.88 m,
.
Ž
.
Ž
.
1H, Me2C H , 4.10 d, 1H, Js10.3 Hz, iPrC H , 4.18
Ž
Ž
.
Ž
Ž
..
Ž
.
s, 5H, cp , 4.13 m, 4H, cp subst. , 4.58 and 4.69
2=d, 1H each, Js15.5 Hz, C H2 Ph , 4.85 dd, 1H,
.
Ž
.
Ž
J1 s2.3 Hz, J2 s9.0 Hz, Fc–C H , 7.90 d, br, 1H,
.
Ž
.
Ž
.
Ž
.
Js9.0 Hz, NH , 6.96 m, 2H, Ph , 7.13 m, 3H, Ph ,
dissolved in cyclohexanerethyl acetate 5:1 80 ml and
13
Ž
Ž
.
Ž
.
Ž
.
7.40 m, 5H, Ph . C NMR CDCl3, 90.55 MHz : 19.9,
the solution filtered over silicagel 20 g . After evapora-
.
Ž
.
Ž
.
20.3 Me2CH , 28.9 Me2CH , 26.2, 26.4, 27.9, 28.4
Ž
tion of the solvent, the product 3.77 g, 82% consisted
of a 1:1 mixture of diastereoisomers which were sepa-
.
Ž
.
Ž
CH2 , cyclohexane , 43.6 CH, cyclohexane , 53.4
Ž
.
Ž
.
Ž
.
Ž
Ž
Ž
CH2 Ph , 56.0 Fc–CH , 73.5 CH–iPr , 68.7 cp un-
.. ..
rated by chromatography silica gel, hexanerdiethyl
Ž
.
subst. , 66.0, 67.0, 67.2, 67.4 CH, cp subst. , 88.0
..
ether 3:1 .
Isomer I Rf 0.39 , m.p. 145–1508C. 1H NMR
Ž
Ž
Ž
.
Ž
.
Cq, cp subst. , 126.3–136.7 8 signals, Ph , 169.8,
Ž
.
Ž
.
Ž
.
173.7 C5O . Found: C, 73.0; H, 7.4; N,4.6%;
C36 H42 FeN2O2 requires C, 73.2; H, 7.2; N, 4.7%.
CDCl3, 360 MHz : 0.86 s, 9H, Me3C , 1.58, 1.81,
Ž
.
Ž
Ž
1.83 3=s, 3H each, CH3 , 3.39, 3.53 2=d, 1H each,
1
Ž
.
Ž
.
.
Ž
.
Isomer II Rf 0.48 , m.p. 2088C. H NMR CDCl3,
Js16.0 Hz, CH2 , 4.09 s, 1H, CH , 4.14 s, 5H, cp ,
.
Ž
.
Ž
Ž
.. ..
Ž
Ž
360 MHz : 0.80–1.75 m, 11H, cyclohexane , 1.08 and
4.12 m, 2H, cp subst. , 4.19 m, 2H, cp subst. , 4.69
Ž
.
Ž
Ž
.
Ž
1.14 2=d, 3H each, Js6.4 Hz, Me2CH , 3.15 m,
d, 1H, Js9.6 Hz, Fc–C H , 9.48 m, br, 1H, Js9.6
13
.
Ž
.
Ž
.
Ž
.
Ž
.
1H, Me2C H , 3.67 d, 1H, Js11.1 Hz, iPrC H , 4.19
Hz, NH . C NMR CDCl3, 90.55 MHz : 26.7 Me3C ,
Ž
.
Ž
Ž
..
Ž
.
Ž
.
Ž
Ž
.
s, 5H, cp , 4.12 m, 4H, cp subst. , 4.51, 4.69 2=d,
28.6, 28.7, 29.4 CH3 , 35.7 Me3C , 53.6 CH , 58.1
.
Ž
Ž
.
Ž
Ž
..
.
1H each, Js15.5 Hz, C H2 Ph , 4.79 dd, 1H, J1 s3.0
Fc–CH , 68.5 cp unsubst. , 66.3, 67.5 Cq , 66.3,
..
.
Ž
Ž
Ž
Ž
.
.
Ž
Hz, J2 s8.5 Hz, Fc–C H , 8.40 d, br, 1H, Js8.5 Hz,
70.1 CH, cp subst. , 76.4 CH–N , 89.0 Cq,
.
Ž
.
Ž
.
Ž
Ž
..
Ž
NH , 7.19 m, 2H, Ph , 7.30 m, 3H, Ph , 7.43 m, 5H,
cp subst. , 163.3, 173.6 C5O . Found: C, 61.3; H,
7.1; N, 5.8%; C24 H32 FeN2O2 S requires C, 61.5; H,
6.9; N, 6.0%.
Ph . 13C NMR CDCl3, 90.55 MHz : 19.2, 20.0
.
Ž
.
Ž
.
Ž
.
Ž
Me2CH , 28.5 Me2CH , 25.8, 25.9, 28.0, 28.1 CH2 ,
1
.
Ž
.
Ž
.
Ž
.
Ž
cyclohexane , 43.6 CH, cyclohexane , 52.6 CH2 Ph ,
..
Isomer II Rf 0.34 , oil. H NMR CDCl3, 360
Ž
.
Ž
.
Ž
Ž
.
Ž
.
Ž
54.4 Fc–CH , 76.8 CH–iPr , 68.4 cp unsubst. ,
MHz : 0.84 s, 9H, Me3C , 1.68, 1.83, 1.84 3=s, 3H
Ž
Ž
Ž
..
Ž
.
Ž
65.6, 66.6, 67.0, 67.2 CH, cp subst. , 88.3 Cq,
..
each, CH3 , 3.34, 3.52 2=d, 1H each, Js16.0 Hz,
Ž
.
.
Ž
Ž
.
Ž
Ž
..
Ž
cp subst. , 126.3–136.3 8 signals, Ph , 168.7, 173.7
CH2 , 4.14 s, 5H, cp , 4.13 m, 2H, cp subst. , 4.19
..
Ž
.
Ž
Ž
.
C5O . Found: C, 73.3; H, 7.0; N, 4.7%;
m, 2H, cp subst. , 4.24 s, 1H, CH , 4.84 d, 1H,
.
Ž
C36 H42 FeN2O2 requires C, 73.2; H, 7.2; N, 4.7%.
Js10.0 Hz, Fc–C H , 9.11 m, br, 1H, Js10.0 Hz,
13
.
Ž
.
Ž
.
NH . C-NMR CDCl3, 90.55 MHz : 26.5 Me3C ,
( )
Ž
.
Ž
..
.
Ž
.
4.2.2. Compound 2
28.5, 28.7, 29.2 CH3 , 36.9 Me3C , 53.6 CH2 , 58.1
Ž
.
Ž
Ž
.
Ž
Ž
Ž
.
2-Methylpropanal 0.72 g, 10 mmol , b-alanine 0.89
Fc–CH , 68.7 cp unsubst. , 66.7, 66.8 Cq , 66.2,
..
.
Ž
Ž
Ž
.
.
Ž
g, 10 mmol , and 1-isocyano-2,2-dimethyl-propylferro-
cene 2.81 g, 10 mmol were dissolved in dry methanol
66.9 CH, cp subst. , 75.9 CH–N , 87.3 Cq,
Ž
.
Ž
..
Ž
cp subst. , 164.0, 173.7 CsO . Found: C, 61.2; H,
7.0; N, 5.8%; C24 H32 FeN2O2 S requires C, 61.5; H,
6.9; N, 6.0%.
Ž
.
20 ml and stirred for 5 h at room temperature. The
Ž
.
precipitated product 3.71 g, 90% was dissolved in
Ž
.
Ž
.
chloroform 50 ml and filtered over silica gel 20 g .
After evaporation of the solvent, the residue consisted
of a 3:1 mixture of diastereoisomers. The main isomer
was isolated in pure form by recrystallization from
4.3. Gold complexes
[
(
)( )] ( )
4.3.1. Au CNCH2 Fc PPh3 Cl 4
acetone. Yield 2.26 g 60% , m.p. 2128C. 1H NMR
Ž
.
w
Ž
.
x
Ž
.
To a solution of AuCl PPh3 0.15 g, 0.30 mmol in
Ž
.
Ž
.
Ž
.
Ž
CDCl3, 360 MHz : 0.82 s, 9H, Me3C , 1.06, 1.08
THF 30 ml under nitrogen was added isocyano-meth-
Ž
.
Ž
.
2=d, 3H each, Js6.6 Hz, Me2CH , 2.38 m, 1H,
ylferrocene 0.14 g, 0.60 mmol . The solution was
heated to reflux for two days. After cooling, the solution
was concentrated. Pentane was added dropwise until a
.
Ž
.
Me2C H , 2.92 t, 2H, Js4.0 Hz, C H2–N , 3.47, 3.59
Ž
.
Ž
Ž
..
2=m, 1H each, C H2–CO , 4.18 s, 5H, cp unsubst. ,

(
)
Y.-Y. Tong et al.rJournal of Organometallic Chemistry 552 1998 17–21
21
yellow precipitate appeared. It was filtered off and dried
Acknowledgements
in a vacuum. The analytical sample contains 1r2
The authors wish to thank Dr. Taha El-Shihi and Dr.
Roland Obrecht for performing some experiments, and
molecule of pentane per molecule of the complex. IR
1
y1
Ž
.
Ž
.
Ž
.
KBr 2140 cm , n CN . H NMR CDCl3, 300 MHz :
Prof. Ivar Ugi, TU Munchen, for general support. Fi-
Ž
Ž
..
Ž
¨
4.15 s, 5H, cp unsubst. , 3.98, 4.33 2=s, 2H each,
nancial support by Deutscher Akademischer Austausch-
dienst, JNICT and the PEDIP and PRAXIS XXI pro-
.
Ž
substituted cyclopentadienyl , 4.60, 4.68 broad, 2=d,
.
Ž
.
Ž
1H each, Js10 Hz, CH2 , 7.60 m, 6H, Ph , 7.73 m,
31
Ž
grammes Portugal, Y.-Y. Tong, PEDIP research fel-
.
Ž
.
Ž
6H, Ph , 7.85 m, 3H, Ph . P NMR CDCl3, 121.4
.
lowship is also gratefully acknowledged.
.
MHz : 16.4. Found: C, 52.4; H, 3.6; N, 2.3%;
C32.5H32 AuClFeNP requires C, 51.6; H, 4.3; N, 1.9%.
References
[
{
( )
a n d
}
(
)][
] (
( )
4.3.2. Au CNCH R Fc PPh3 BPh4
RsiPr 5 ,
2
( ))
6
[
{
(
)
c H e x
A u C N E tO C C s
w x
1
T. El-Shihi, F. Siglmuller, R. Herrmann, M.F.N.N. Carvalho,
¨
A.J.L. Pombeiro, J. Organomet. Chem. 335 1987 239.
}
(
)][
] ( )
CHFc PPh3 BPh
7
Ž
.
w4
Ž
.
x
Ž
.
w x
2
To a solution of AuCl PPh3 0.15 g, 0.30 mmol in
THF 30 ml under nitrogen was added the correspond-
ing isocyanide 0.60 mmol , followed by Na BPh4
0.42 g, 1.2 mmol . The mixture was stirred for 7 days
at room temperature. After concentration, the residue
was dissolved in dichloromethane. After filtering, di-
ethyl ether was added to the solution until a yellow
precipitate appeared. It was filtered off and dried in a
vacuum.
T. El-Shihi, F. Siglmuller, R. Herrmann, M.F.N.N. Carvalho,
A.J.L. Pombeiro, Port. Electrochim. Acta 5 1987 179.
¨
Ž
.
Ž
.
w x
3
Ž
.
I. Ugi Ed. , Isonitrile Chemistry, Academic Press, New York,
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Ž
.
w
x
Ž
.
w x
4
R. Urban, D. Marquarding, I. Ugi, Hoppe-Seyler’s Z. Physiol.
Chem. 359 1978 1541.
Ž
.
w x
Ž .
5
w x
6
R. Urban, Tetrahedron 35 1979 1841.
I. Ugi, Angew. Chem. 94 1982 826.
R. Urban, G. Eberle, D. Marquarding, D. Rehn, H. Rehn, I. Ugi,
Angew. Chem. 88 1976 644.
Ž
.
w x
7
Ž
.
w x
Ž .
8
w x
9
W.E. Watts, J. Organomet. Chem. Libr. 7 1979 399.
Ž .
P.M. Treichel, Adv. Organomet. Chem. 11 1973 21.
1
y1
Ž .
Ž
.
.
Ž
.
RsiPr 5 : IR KBr 2180 cm , n CN . H NMR
Ž
Ž
w
w
x
Ž
.
CDCl3, 300 MHz : 0.80, 0.94, 0.99, 1.03 4=d, 1.5H
10 F. Bonati, G. Minghetti, Inorg. Chim. Acta 9 1974 .
x
11 E. Singleton, H.E. Oosthuizen, Adv. Organomet. Chem. 22
.
Ž
.
each, Js6.6 Hz, C H3 , 1.30 m, 1H, Me2C H , 4.85
Ž
.
1983 209.
Ž
.
Ž
Ž
..
Ž
m, 1H, CN–C H , 4.25 s, 5H, cp unsubst. , 4.17,
..
w
w
x
Ž
.
12 T. Hayashi, in: A. Togni, T. Hayashi Eds. , Ferrocenes, VCH
Ž
Ž
4.30 2=m, 2H each, cp subst. , 7.05–7.90 m, 35H,
Publ., Weinheim, 1995.
31
.
Ž
.
Ph . P NMR CDCl3, 121.4 MHz : 43.4. Found: C,
67.9; H, 5.5; N, 2.1%; C57 H52 AuBFeNP requires C,
65.5; H, 5.0; N, 1.3%.
x
13 N. Farrell, Transition Metal Complexes as Drugs and
Chemotherapeutic Agents, Chaps. 6 and 11, Kluwer Academic
Publ., Dordrecht, 1989.
RscHex 6 : IR KBr 2180 cmy1, n CN . 1H
w
w
w
w
w
x
14 Y.-Y. Tong, A.J.L. Pombeiro, D.L. Hughes, R.L. Richards,
Ž .
Ž
.
Ž
.
Ž
.
Transition Met. Chem. 20 1995 372.
Ž
.
Ž
.
NMR CDCl3, 300 MHz : 0.95 m, 4H, cHex ; 1.23
x
15 M. Nakamoto, W. Hiller, H. Schmidbaur, Chem. Ber. 126
Ž
.
Ž
Ž
.
Ž
m, 4H, cHex ; 1.70 m, 2H, cHex ; 5.80 m, 1H,
..
Ž
.
1993 605.
.
Ž
Ž
x
Ž
.
cHex ; 4.17 s, 5H, cp unsubst. ; 4.08 m, 4H,
16 L.G. Vaughan, W.A. Sheppard, J. Am. Chem. Soc. 91 1969
31
6151.
Ž
..
Ž
.
Ž
cp subst. ; 6.95–7.80 m, 35H, Ph . P NMR CDCl3,
121.4 MHz : 38.6. An analytically pure sample could
x
17 G. Minghetti, F. Bonati, Atti. Accad. Naz. Lincei, Cl. Sci. Fis.
.
Ž
.
Mat. Nat. Rend. 49 1970 287.
not be obtained.
x
18 C.A. McAuliffe, R.V. Parish, P.D. Randall, J. Chem. Soc.,
w
Ž
Ž
.
.Ž
.
xw
x
Ž .
7 : IR
Au CN EtO2C C s CHFc PPh3 BPh4
Ž
.
Dalton Trans. 1979 1730.
1
y1
Ž
.
Ž
Ž
.
Ž
.
w
w
x
Ž
.
KBr 2100 cm , n CN . H NMR CDCl3, 300 MHz :
19 G.E. Coates, C. Perkin, J. Chem. Soc. 1953 421.
x
20 M.E.N.P.R.A. Silva, A.J.L. Pombeiro, J.J.R. Frausto da Silva,
.
Ž
´
1.25 t, 3H, Js7.2 Hz, CH3 , 4.19 qua, 2H, Js7.2
R. Herrmann, N. Deus, T.J. Castilho, M.F.C.G. Silva, J.
.
Ž
Ž
..
Ž
Hz, CH2 , 4.17 s, 5H, cp unsubst. , 4.31, 4.47 2=t,
..
Ž
.
Organomet. Chem. 421 1991 75.
21 R. Obrecht, R. Herrmann, I. Ugi, Synthesis 1985 400.
22 A.K. Al-Sa’ady, C.A. McAuliffe, R.V. Parish, J.A. Sandbank,
Ž
Ž
2H each, Js1.8 Hz, cp subst. , 7.10–7.90 m, 36H,
w
w
x
x
Ž
.
31
.
Ž
.
PhqsCH . P-NMR CDCl3, 121.4 MHz : 43.9. An
Ž
.
analytically pure sample could not be obtained.
Inorg. Synth. 23 1985 191.