Synthesis and reactivity of acyclic (pentadienyl)iron(1+) cations: Model studies for the preparation of the 8E,10Z,16E,18E-tetraene segment of macrolactin A

Article abstract of DOI:10.1016/S0020-1693(99)00368-0

The dicarbonyl(1,2-dimethylpentadienyl)triphenylphosphineiron(1+) cation (11) has been prepared from methyl 4-methyl-2E,4E-hexadienoate in four steps. The cation (11) reacts with hydride and carbon nucleophiles in a regiospecific fashion to afford (3-methyl-2E,4Z-diene)iron complexes. Dicarbonyl(3-methyl-7-nitro-2E,4Z-heptadiene)triphenylphosphineiron (15), the product from the reaction of 11 with nitromethane anion, has been utilized as a precursor for nitrile oxide-olefin cyclocondensations.

Full text of DOI:10.1016/S0020-1693(99)00368-0

www.elsevier.nl/locate/ica
Inorganica Chimica Acta 296 (1999) 261–266
Note
Synthesis and reactivity of acyclic (pentadienyl)iron(1+) cations:
model studies for the preparation of the 8E,10Z,16E,18E-tetraene
segment of macrolactin A
Abdel-Aziz S. El-Ahl 1, Young K. Yun 2, William A. Donaldson *
Department of Chemistry, Marquette Uni6ersity, P.O. Box 1881, Milwaukee, WI 53201-1881, USA
Received 9 June 1999; accepted 16 August 1999
Abstract
The dicarbonyl(1,2-dimethylpentadienyl)triphenylphosphineiron(1+) cation (11) has been prepared from methyl 4-methyl-
2E,4E-hexadienoate in four steps. The cation (11) reacts with hydride and carbon nucleophiles in a regiospecific fashion to afford
(3-methyl-2E,4Z-diene)iron complexes. Dicarbonyl(3-methyl-7-nitro-2E,4Z-heptadiene)triphenylphosphineiron (15), the product
from the reaction of 11 with nitromethane anion, has been utilized as a precursor for nitrile oxide–olefin cyclocondensations.
© 1999 Elsevier Science S.A. All rights reserved.
Keywords: (1,3-Diene)iron complexes; Bis-iron tetraene complexes; Nitrile oxide–olefin cycloadditions; Isoxazolines
reported on a fundamentally different strategy for the
preparation of the C11ꢀC24 segment of 1 which relies
on the ability of an Fe(CO)3 adjunct to control the
introduction of the remote asymmetric centers at C15
and C23 [3]. We [3,4] and others [5] have demonstrated
that intermolecular nitrile oxide–(triene)Fe(CO)3 cyclo-
condensation methodology can be utilized for the
diastereoselective introduction of an asymmetric center
adjacent to a complexed diene. In conformity to this
strategy, disconnection of 1 at the anti-1,3-diol func-
tionality generates a nitro-diene fragment 2 and a triene
fragment 3 (Scheme 1). Furthermore, the 8E,10Z-diene
1. Introduction
Macrolactin A (1) is a 24-membered polyene macro-
lide isolated from a taxonomically-undefined deep sea
bacterium [1a]. This compound exhibits antiviral activ-
ity against Herpes Simplex I and II and against HIV.
Unfortunately, the culturing of this bacterium has been
‘unreliable’ [1b]. The structure of 1 was assigned on the
basis of NMR spectroscopy [1a], and by chemical
degradation and synthesis of the fragments [1b]. Re-
cently total syntheses by Smith and Ott [2a] and by
Carreira’s group [2b] have corroborated the structural
assignment. These syntheses, as well as work by Boyce
and Pattenden [2c] and by Rychnovsky and Pickering
[2d] have utilized Pd-coupling methodology for con-
struction of the diene linkages. We have previously
* Corresponding author. Tel.: +414-288 7374; fax: +414-288
7066.
E-mail address: donaldsonw@mu.edu (W.A. Donaldson)
1 Present address: Chemistry Department, Faculty of Science, Man-
soura University, Mansoura, Egypt.
2 Present address: Argonaut Technologies, 887 Industrial Road,
Suite G, San Carlos, CA 94070, USA.
Scheme 1.
0020-1693/99/$ - see front matter © 1999 Elsevier Science S.A. All rights reserved.
PII: S0020-1693(99)00368-0

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A.-A.S. El-Ahl et al. / Inorganica Chimica Acta 296 (1999) 261–266
shifts for H-4 and H-5exo may be attributed to the
anisotropic effect of the aryl groups of the
triphenylphosphine ligand.
The reaction of 11 with sodium cyanoborohydride
gave the E,Z-diene complex 12 resulting from nucleo-
philic attack at C5 (Scheme 3). The structure of 12 was
1
assigned on the basis of its H NMR spectral data. In
1
particular, the H NMR spectrum of 12 exhibits three
Scheme 2.
signals at l 2.02 (s), 1.45 (d) and 1.06 (d) ppm corre-
sponding to the three methyl groups. The doublet at l
3.68, corresponding to H-4, is shifted considerably up-
field as compared to the corresponding signal for the
Fe(CO)3 ligated complex (l 5.09 ppm) [6b]. This upfield
shift may be attributed to the anisotropic effects of the
triphenylphosphine ligand situated in the basal position
of complex 12.
segment 2 might be generated via nucleophilic addition
to a (pentadienyl)iron cation.
We have previously prepared the substituted (penta-
dienyl)iron cations 4–7 [6]. Nucleophilic attack on
these cations, at the terminal positions, occurs with
regioselectivity as indicated by the arrows. In these
studies, we found that substitution of a carbonyl ligand
by triphenylphosphine resulted in improved regioselec-
tivity (cf. 4 versus 7). Herein, we report on the prepara-
tion and reactivity of dicarbonyl(1,2-dimethylpenta-
dienyl)triphenylphosphineiron(1+) cation (11) (the
Fe(CO)2PPh3 ligated analog of 6) and the application
of products from these reactions in the model studies
for the preparation of the 8E,10Z,16E,18E-tetraene
segment of macrolactin A.
Reaction of 11 with lithium dimethyl malonate or
lithium ethyl nitroacetate gave the E,Z-diene complexes
13 or 14, respectively. The structures of 13 and 14 were
1
assigned by comparison of their H NMR spectral data
with that of 12. Complex 14 is produced as a 1:1
mixture of diastereomers at C2. Finally, reaction of 11
with the anion derived from the deprotonation of ni-
tromethane with n-butyl lithium gave the 1° nitro diene
complex 15. The structure of 15 was assigned on the
1
basis of its H NMR spectral data. In particular, the
appearance of the signal for H-4 as a doublet at l 3.82
was indicative of the 3-methyl-2E,4Z-pentadienyl frag-
ment, while coupling between the H-7 and H-6 protons
indicated the formation of the CꢀC bond between
carbons 6 and 7. While O-alkylation is frequently en-
countered for nitroalkane monoanions [8], C-alkylation
has been previously demonstrated using tricarbonyl(cy-
clohexadienyl)iron(1+) cations as the electrophile [9].
From these results, cation 11 was found to react with
nucleophiles in a regioselective fashion and the regiose-
lectivity is the same as that observed for cation 6.
Generation of the nitrile oxide derived from the 1°
nitro complex 15 (PhNCO/NEt3) [10] in the presence of
allylbenzene gave the isoxazoline 16 (Scheme 4). The
2. Results and discussion3
Ligand substitution [7] of (methyl 4-methyl-2,4-hexa-
dienoate)Fe(CO)3 (8) gave the Fe(CO)2PPh3 ligated
complex 9 in good isolated yield (Scheme 2). Reduction
of 9 gave the dienol complex 10. Protic dehydration of
10 gave the (1,2-dimethylpentadienyl)Fe(CO)2PPh3
cation (11) in excellent yield (Scheme 2). Cation 11 was
+
1
signals for H-4 appear as two doublets in the H NMR
spectrum of 16 (l 3.78 and 3.75 ppm), indicating the
1
assigned a cisoid geometry on the basis of its H NMR
spectral data. In particular, the coupling between H-3
and H-4 (7.2 Hz) is characteristic of a cisoid relation-
ship between these two protons. We [6a] and others [7]
have reported that for (1-substituted pentadienyl)-
+
Fe(CO)2PPh3 cations, the bulky triphenylphosphine
ligand occupies the basal site opposite to the C1 sub-
stituent. This also appears to be the case for 11; nota-
bly, the chemical shifts for H-4 and H-5exo of 11 are
approximately 1.0 and 1.3 ppm upfield of those for the
corresponding Fe(CO)3 ligated cation 6 [6b] while the
signal for H-1 of 11 is shifted upfield only 0.2 ppm
compared to the same signal for 6. The greater upfield
3 All compounds prepared are racemic mixtures of enantiomers.
Only one enantiomer has been diagrammed for clarity.
Scheme 3.

A.-A.S. El-Ahl et al. / Inorganica Chimica Acta 296 (1999) 261–266
263
oxidative decomplexation of 19 afforded the bis-dienyl
isoxazoline 22 (Scheme 4). The stereochemical assign-
ment for 22 was based upon the magnitude of olefinic
vicinal proton coupling constants observed.
In summary, a methodology for the preparation of
the 8E,10Z,16E,18E tetraene segment of macrolactin A
has been developed. Application of this methodology to
the asymmetric synthesis of 1 is in progress.
3. Experimental
3.1. General data
All reactions were performed in flame-dried glass-
ware under a nitrogen atmosphere. All melting point
measurements were carried out on a Mel-Temp appara-
1
tus and are uncorrected. All H and 13C NMR spectra
were recorded at 300 and 75 MHz, respectively using a
GE Omega GN-300 spectrometer. Elemental analyses
were performed by Midwest Microlabs, Indianapolis,
IN. High resolution mass spectra were performed at
Washington University Resource for Biomedical and
Bio-organic Mass Spectrometry. Dry tetrahydrofuran
(THF) and dry ether were distilled from potassium and
sodium benzophenone ketyl, respectively. Anhydrous
hexanes were purchased from Aldrich Chemical. All
other solvents were spectral grade and were used with-
out further purification. Tricarbonyl(1,3E,5E-hepta-
triene)iron (18) was prepared by the literature
procedure [4b].
Scheme 4.
formation of a 1:1 mixture of diastereomers at C-9.
Thus the diene–iron functionality present in 15 does
not exert any facial preference for 1,3-dipolar cycload-
dition to allylbenzene. This is not surprising since the
diastereoselectivity of nitrile oxide–olefin cycloaddi-
tions are little influenced by the presence of an a-asym-
metric center in the nitrile oxide component [11].
Oxidative decomplexation of 16 gave the dienyl isoxa-
zoline 17.
Similarly, reaction of the nitrile oxide derived from
rac-15 under Mukaiyama conditions with the triene–
iron complex rac-18 gave the bimetallic tetraene isoxa-
zoline 19 (Scheme 4). While four sets of racemic
diastereomers are possible, examination of the NMR
spectra of 19 indicated the presence of only two
diastereomers. The „-exo relative stereochemistry of
the C8–C14 segment was assigned by comparison of
the 13C NMR chemical shifts for C-8, C-9, and C-10
with those of the known „-exo and „-endo dienylisoxa-
zoline complexes 20 and 21 [4a]. In particular, the
diastereomeric signals for 19 (approximately l 44, 84
and 60 ppm) more closely match those of 20 (l 45.0,
83.6 and 59.4 ppm) than those of 21 (l 48.0, 85.5 and
63.1 ppm). Thus, the (tricarbonyl)iron adjunct of 18
controls the diastereoselectivity of the cyclocondensa-
tion as has been observed in other cases [4,5]. Finally,
3.2. Tricarbonyl(methyl
4-methyl-2E,4E-hexadienoate)iron (8)
To
a solution of methyl 4-methyl-2E,4E-hexa-
dienoate (3.00 g, 21.4 mmol) in benzene (120 ml) was
added solid Fe2(CO)9 (11.7 g, 32.1 mmol). The mixture
was stirred at r.t. for 1 h, and then heated at reflux for
10 h. The reaction mixture was cooled, additional
Fe2(CO)9 (3.9 g, 10.7 mmol) was added, and the mix-
ture was heated at reflux for an additional 5 h. The
mixture was cooled, filtered through filter-aid, and the
filter bed was washed with CH2Cl2. The combined
organic phases were concentrated and the residue
purified by column chromatography (SiO2, hexanes–
ethyl acetate (10:1)) to afford 8 as a yellow solid (4.43
g, 74%). Anal. Calc. for C11H12O5Fe: C, 47.35; H, 3.97.
1
Found: C, 47.56; H, 4.13%. H NMR (CDCl3): l 5.68
(d, J=7.8 Hz, H-3), 3.64 (s, OMe), 2.16 (s, Me-4), 1.47
(d, J=6.3 Hz, Me-6), 1.29 (q, J=6.3 Hz, H-5), 0.85 (d,
J=7.8 Hz, H-2). 13C{1H} (CDCl3): l 173.3 (C-1), 102.7
(C-4), 83.5 (C-3), 59.3 (C-5), 51.4 (OMe), 42.7 (C-2),
17.8 (Me-4), 15.8 (Me-6).

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3.3. Dicarbonyl(methyl 4-methyl-2E,4E-hexadienoate)-
triphenylphosphineiron (9)
the precipitate dissolved in a minimal amount of
CH3NO2 (1.5 ml). This concentrated solution was
added dropwise to a large excess of Et2O (700 ml). The
resultant precipitate was collected by vacuum filtration
and dried in vacuo to afford 11 as a bright-yellow
powder (2.29 g, 77%). Anal. Calc. for C27H26O2P2F6Fe·
1/2H2O: C, 52.03; H, 4.36. Found: C, 51.77; H, 4.23%.
1H NMR (CD3NO2): l 7.73–7.55 (m, ArH), 6.63 (d,
J=7.2 Hz, H-3), 5.08 (br m, H-4), 2.48 (q, J=6.0 Hz,
H-1), 2.44 (s, Me-2), 2.32 (dt, J=10.3, 4.8 Hz, H-5exo),
1.88 (m, H-5endo), 1.83 (d, J=6.1, Me-1). Peak assign-
ments are made on the basis of 2D COSY-NMR
spectra.
A mixture of tricarbonyl(methyl 4-methyl-2E,4E-
hexadienoate)iron (4.43 g, 15.8 mmol) and
triphenylphosphine (4.91 g, 17.4 mmol) in acetone (75
ml) was heated at reflux for 2 h. Solid trimethylamine
N-oxide (3.52 g, 31.7 mmol) was added and the mixture
was heated at reflux for an additional 1 h. The reaction
mixture was cooled and extracted with ether. The com-
bined extracts were dried and concentrated. The residue
was purified by column chromatography (SiO2, 3:1
hexanes–ethyl acetate) to afford 9 as a yellow solid
(5.46 g, 67%). Anal. Calc. for C28H27O4PFe: C, 65.39;
H, 5.29. Found: C, 65.34; H, 5.34%. M.p. 156–158°C.
1H NMR (CDCl3): l 7.6–7.4 (m, ArH), 5.64 (br m,
H-3), 3.24 (s, OMe), 2.09 (s, Me-4), 1.12 (d, J=6.3 Hz,
Me-6), −0.30 (br m, H-2 and H-5). 13C{1H} (CDCl3):
l 174.6 (C-1), 135.7 (d, JPꢀC=38.8 Hz, ArC), 132.8 (d,
3.6. Dicarbonyl(3-methyl-2E,4Z-hexadiene)-
triphenylphosphineiron (12)
To a solution/suspension of cation 11 (200 mg, 0.325
mmol) in THF (15 ml) at 0°C was added solid
NaBH3CN (22 mg, 0.35 mmol) in one portion. The
mixture was stirred at 0°C for 1 h, warmed to r.t. and
stirred at 23°C for 1 h. Water (15 ml) was added and
the mixture was extracted with Et2O (3×20 ml). The
combined organic extracts were dried (MgSO4) and
concentrated. The residue was purified by column chro-
matography (SiO2, 10:1 hexanes–ethyl acetate) to af-
ford 12 as a yellow solid (80 mg, 52%). 1H NMR
(CDCl3): l 7.60–7.32 (m, ArH), 3.68 (d, J=6.6 Hz,
H-4), 2.02 (s, Me-3), 1.97–1.94 (m, H-2), 1.62–1.50 (m,
H-5), 1.45 (dd, J=1.8, 6.5 Hz, Me-1), 1.06 (dd, J=1.8,
7.2, Me-6). 13C{1H} (CDCl3): l 136.5 (d, JPꢀC=37.6
Hz, ArC), 133.1 (d, JPꢀC=9.7 Hz, ArC), 129.3 (ArC),
128.0 (d, JPꢀC=8.5, ArC), 105.1 (C-3), 89.2 (C-4), 50.1
(d, JPꢀC=6.1 Hz) and 48.5 (d, JPꢀC=7.3 Hz, C-2 and
C-5), 18.1 (Me-3), 16.4 (Me-1), 14.2 (Me-6).
JPꢀC=10.9 Hz, ArC), 129.4 (ArC), 128.1 (d, JPꢀC=9.7,
ArC), 101.7 (C-4), 84.5 (C-3), 61.8 (C-5), 50.6 (OMe),
45.7 (C-2), 18.4 (Me-4), 15.0 (Me-6).
3.4. Dicarbonyl(4-methyl-2E,4E-hexadien-1-ol)-
triphenylphosphineiron (10)
To a solution of 9 (3.79 g, 7.37 mmol) in anhydrous
hexanes (45 ml), cooled to −30°C, was added a solu-
tion of DIBAL in hexanes (15 ml, 1.0 M, 15 mmol).
The reaction mixture was stirred at this temperature for
90 min, and then methanol (20 ml) was cautiously
added. The mixture was diluted with saturated aqueous
NH4Cl and extracted with ethyl acetate. The combined
extracts were washed with brine, dried and the solvent
evaporated. The residue was purified by column chro-
matography (SiO2, 3:1 hexanes–ethyl acetate) to afford
10 as a yellow solid (1.96 g, 56%). Anal. Calc. for
C27H27O3PFe: C, 66.68; H, 5.60. Found: C, 66.30; H,
3.7. Dicarbonyl [dimethyl (4%-methyl-2%Z,4%E-
hexadienyl)propandioate]triphenylphosphineiron (13)
1
5.41%. M.p. 128–130°C. H NMR (CDCl3): l 7.56–
7.36 (m, ArH), 4.99 (d, J=6.9 Hz, H-3), 3.38 (br t,
H-1), 3.26 (dd, J=4.3, 11.5 Hz, H-1%), 2.10 (s, Me-4),
1.03 (d, J=6.3 Hz, Me-6), 1.00 (br s, OH), −0.38 (m,
H-2 and H-5). 13C{1H} (CDCl3): l 136.4 (JPꢀC=37.5
Hz, ArC), 132.6 (JPꢀC=10.9 Hz, ArC), 129.3 (ArC),
128.2 (JPꢀC=8.5 Hz, ArC), 101.1(C-4), 85.4 (C-3), 65.9
(C-1), 60.5 (C-5), 58.4 (C-2), 18.4 (Me-4), 15.2 (Me-6).
To a solution of lithium dimethyl malonate (0.68
mmol, freshly prepared from dimethylmalonate and
n-butyl lithium) in THF (10 ml) at 0°C was added solid
cation 11 (300 mg, 0.489 mmol) in one portion. The
mixture was stirred at 0°C for 1 h and at 23°C for 18 h.
Water (10 ml) was added and the mixture was extracted
with Et2O (3×20 ml). The combined organic extracts
were dried (MgSO4) and concentrated. The residue was
purified by column chromatography (SiO2, 3:1 hex-
anes–ethyl acetate) to afford 13 as a yellow oil (250 mg,
3.5. Dicarbonyl(1,2-dimethylpentadienyl)-
triphenylphosphineiron(1+) hexafluorophosphate (11)
1
To a solution of 10 (2.35 g, 4.85 mmol) in Ac2O (6.5
ml) at 0°C was added dropwise a cold solution of HPF6
(4 ml, 60% solution) in Ac2O (2.5 ml). The mixture was
stirred for 30 min, during which time a bright-yellow
precipitate formed. The mixture was added to a large
excess of Et2O (600 ml). The ether was decanted and
87%). H NMR (CDCl3): l 7.52–7.33 (m, ArH), 3.66–
3.57, 3.60 and 3.55 (m and 2×s, H-3% and 2×OMe),
2.96 (t, J=7.5 Hz, H-1), 2.29 (m, H-1%), 2.00 (s, Me-4%),
1.93 (m, H-5%), 1.69 (m, H-1% and H-2%), 1.44 (dd,
J=1.8, 6.3 Hz, Me-6%). 13C{1H} (CDCl3): l 214.0 and
213.7 (MꢀCO), 169.0 (CO2Me), 135.8 (d, JPꢀC=37.8

A.-A.S. El-Ahl et al. / Inorganica Chimica Acta 296 (1999) 261–266
265
Hz, ArC), 132.8 (d, JPꢀC=9.7 Hz, ArC), 129.3 (ArC),
127.9 (d, JPꢀC=9.7 Hz, ArC), 105.9 (C-4%), 86.7 (C-3%),
55.0 (CHE2), 52.0 (OMe), 50.2 (d, JPꢀC=8.5 Hz) and
49.9 (d, JPꢀC=6.0 Hz, C-2% and C-5%), 29.3 (C-1%), 17.9
(Me-4%), 16.2 (Me-6%).
130.5 (ArC), 130.0 (d, JPꢀC=7.9 Hz, ArC), 106.9 (C-3),
87.0 (C-4), 78.5 (CH2NO2), 50.1 (d, JPꢀC=7.8 Hz) and
49.2 (d, JPꢀC=8.2 Hz) (C-2 and C-5), 28.7 (C-6), 18.9
(Me-3), 17.2 (Me-1).
3.10. Preparation of 16 6ia nitrile oxide–allylbenzene
cyclocondensation
3.8. Dicarbonyl (ethyl 6-methyl-2-nitro-4Z,6E-
octadienoate)triphenylphosphineiron (14)
To a solution of iron complex 15 (115 mg, 0.218
mmol), allylbenzene (31 mg, 0.26 mmol) and phenyl
isocyanate (35 ml, 0.33 mmol) in benzene (10 ml) was
added triethylamine (15 ml). The reaction mixture was
stirred for 48 h, diluted with water (10 ml) and ex-
tracted several times with ether. The combined organic
extracts were washed with H2O, followed by brine,
dried (MgSO4) and concentrated. The product was
extracted from the residue by dissolving in hexanes (in
which the white crystalline by-product is not soluble).
The combined hexane extracts were purified by column
chromatography (SiO2, 9:1 hexane–ethyl acetate to give
16 as a yellow oil (39.5 mg, 29%). This was determined
to be an equimolar mixture of diastereomers by 1H
NMR spectroscopy. FAB-HRMS. Found: 573.1884.
To a solution of lithium ethyl nitroacetate (0.34
mmol, freshly prepared from ethyl nitroacetate and
n-butyl lithium) in THF (10 ml) at 0°C was added solid
cation 11 (150 mg, 0.245 mmol) in one portion. The
mixture was stirred at 0°C for 1 h and at 23°C for 18 h.
Water (10 ml) was added and the mixture was extracted
with Et2O (3×20 ml). The combined organic extracts
were dried (MgSO4) and concentrated. The residue was
purified by column chromatography (SiO2, 3:1 hex-
anes–ethyl acetate) to afford 14 as a yellow oil (140 mg,
95%). This was determined to be an equimolar mixture
1
1
of diastereomers by H NMR spectroscopy. H NMR
(CDCl3): l 7.54–7.34 (m, ArH), 4.69 and 4.59 (2×dd,
J=5.1, 9.6 Hz, CH(NO2)CO2Et), 4.23–4.09 (m,
OCH2CH3), 3.78 and 3.71 (2×d, J=7.2 Hz, H-5), 2.61
and 2.40 (2×m, H-3), 2.03 and 2.02 (2×s, Me-6), 1.85
(m, H-7), 1.62–1.38 (m, H-3%, H-4, Me-8%), 1.24 and
1.21 (2×t, J=7 Hz, CH2CH3). 13C{1H} (CDCl3,
diastereomeric signals in square brackets): l 214.8 and
214.6 (MꢀCO), 164.9 [164.8] (C1), 136.4 [136.3] (d,
1
Calc. for C35H36NOPFe (M-2CO): 573.1884. H NMR
(CDCl3): l 7.58–7.2 (m, ArH), 4.61 (m, H-9), 3.78 and
3.75 (2×d, J=8.8 Hz, H-4), 2.94 and 2.92 (2×dd,
J=5.8, 13.5 Hz, H-10), 2.7–2.2 (m, H-6, 2×H-8,
2×H-10), 2.04 and 2.03 (2×s, Me-3), 1.85 (m, H-2),
1.60 (br m, H6%), 1.45 (br d, J=5.5 Hz, Me-1).
JPꢀC=38.7 Hz, ArC), 133.7 (d, JPꢀC=9.7 Hz, ArC),
130.4 (ArC), 129.0 (d, JPꢀC=9.6 Hz, ArC), 107.3
[107.0] (C-6), 91.7 [91.0] (C-2), 86.7 (C-5), 63.5
(OCH2CH3), 50.9 and 47.9 (C-4 and C-7), 31.7 [31.5]
(C-3), 18.8 (Me-6), 17.2 (Me-8), 14.6 (OCH2CH3).
3.11. Isoxazoline (17)
To a solution of iron complex 16 (11 mg, 0.017
mmol) in methanol (5 ml) was added ammonium
cerium nitrate (10 mg, 0.018 mmol) and the mixture
was stirred for 2 h at 23°C. The mixture was poured
into water and this was extracted several times with
ether. The combined ether extracts were dried (MgSO4)
and concentrated. The residue was purified by column
chromatography (SiO2, 10:1 hexanes–ethyl acetate) to
afford 17 as a colorless oil (4 mg, 94%). 1H NMR
(CDCl3): l 7.35–7.15 (ArH), 5.97 (d, J=11.3 Hz,
H-4), 5.43 (br q, J=6.8 Hz, H-2), 5.26 (td, 7.6, 11.7,
H-5), 4.81 (m, H-9), 3.25 (d, J=7.4 Hz, H-6, H-6%),
3.05 (dd, J=5.8, 13.8 Hz, H-10), 2.91 (dd, J=10.0,
17.1 Hz, H-8), 2.81 (dd, J=7.0, 13.8 Hz, H-10%), 2.64
(dd, J=7.4, 17.1 Hz, H-8%), 1.74 (s, Me-3), 1.68 (d,
J=6.8 Hz, Me-1).
3.9. Dicarbonyl (3-methyl-7-nitro-2E,4Z-
heptadiene)triphenylphosphineiron (15)
To a solution of lithium nitromethane (1.22 mmol,
freshly prepared from nitromethane and n-butyl
lithium) in THF (10 ml) at 0°C was added solid cation
11 (500 mg, 0.814 mmol) in one portion. The mixture
was stirred at 0°C for 1 h and at 23°C for 18 h. The
reaction mixture was diluted with water and extracted
with Et2O (3×20 ml). The combined organic extracts
were dried (MgSO4) and concentrated. The residue was
purified by column chromatography (SiO2, 3:1 hex-
anes–ethyl acetate) to afford 15 as a yellow oil (256 mg,
59%). FAB-HRMS. Found: 473.1210. Calc. for
1
C26H28NO2PFe (M-2CO): 473.1207. H NMR (CDCl3):
l 7.58–7.30 (m, ArH), 4.09 (td, J=7.1, 12.3 Hz, H-7),
4.00 (td, J=7.1, 12.3, H-7%), 3.82 (br d, J=7.0 Hz,
H-4), 2.26 (m, H-6), 2.06 (s, Me-3), 1.92–1.72 (m, H-2
and H-5), 1.49 (dd, J=2.0, 6.2, Me-1), 1.20 (m, H-6%).
13C{1H} (CDCl3): l 214.8 and 214.5 (MꢀCO), 136.6 (d,
3.12. Preparation of 19 6ia nitrile oxide–triene
cyclocondensation
To a solution of nitrodiene–iron complex 15 (388
mg, 0.733 mmol), triene–iron complex 18 (189 mg,
JPꢀC=38.9 Hz, ArC), 133.8 (d, JPꢀC=9.2 Hz, ArC),

266
A.-A.S. El-Ahl et al. / Inorganica Chimica Acta 296 (1999) 261–266
0.795 mmol) and phenyl isocyanate (120 ml, 1.1 mmol)
in benzene (7 ml) was added triethylamine (50 ml). The
reaction mixture was stirred for 36 h and then diluted
with water (5 ml) and extracted several times with
ether. The combined organic extracts were washed with
H2O, followed by brine, dried (MgSO4) and concen-
trated. The product was extracted from the residue by
dissolving in hexanes (in which the white crystalline
by-product is not soluble). The combined hexane ex-
tracts were purified by column chromatography (SiO2,
9:1 hexane–ethyl acetate) to give 19 as a golden-yellow
foam (119 mg, 56%). Anal. Calc. for C38H36NO6PFe2·
1/5C6H14: C, 61.74; H, 5.13. Found: C, 62.08; H,
Hz, Me-12) [assignments based on COSY]. 13C{1H}
(CDCl3): l 158.6, 136.8, 134.0, 133.2, 132.0, 131.0,
128.6, 126.3, 122.0, 81.6, 43.5, 28.1, 18.7, 17.0, 14.2.
Acknowledgements
This work was supported by the National Institutes
of Health (GM-42641). Dr El-Ahl thanks the US–
Egypt Binational Fulbright Commission for a Fellow-
ship during which this research was undertaken. Mass
spectrometry was provided by the Washington Univer-
sity Mass Spectrometry Resource, an NIH Research
Resource (Grant No. 1 P41RR0954).
1
5.18%. M.p. 52–53°C. H NMR (CDCl3): l 7.6–7.3
(m, ArH), 5.17 and 5.16 (2×dd, J=4.5, 8.2 Hz, H-11),
5.08 and 5.06 (2×dd, J=4.5, 8.6 Hz, H-12), 4.09 and
4.07 (2×q, J=9.4 Hz, H-9), 3.86 and 3.83 (2×d,
J=7.8 Hz, H-4), 2.8–2.2 (m, H-6, H-6%, H-8, H-8%),
2.06 (s, Me-3), 1.88 (m, H-2), 1.65 (m, H-5), 1.49–1.40
(m, Me-1, Me-14), 1.35 (m, H-10, H-13), additional
signals due to entrained hexanes were observed.
13C{1H} (CDCl3, diastereomeric signals in square
brackets): l 214.7, 214.4, 212.3 (M-CO), 160.7 (C-7),
136.6 (JCP=38 Hz, ArC), 133.7 (JCP=9 Hz, ArC),
130.3 (ArC), 128.8 (JCP=9 Hz, ArC), 106.8 (C-3), 88.0
and 87.1 [87.0] (C4 and C-12), 83.9 [83.8] and 83.6
[83.5] (C9 and C11), 60.3 [60.1] and 59.8 [59.7] (C10
and C-13), 51.4 [51.3] and 49.8 (JCP=9 Hz) [49.6
(JCP=8 Hz)] (C-2 and C-5), 44.3 (C-8), 28.1 (C-6),
19.8, 18.7, 17.0 (Me-1, Me-3, Me-14).
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1
afford 22 as a colorless oil (20.8 mg, 49%). H NMR
(CDCl3): l 6.24 (dd, J=10.4, 15.0 Hz, H-10), 6.00 (m,
H-11), 5.99 (d, J=11.0 Hz, H-3), 5.76 (dq, J=14.8, 6.8
Hz, H-12), 5.57 (dd, J=7.6, 14.9 Hz, H-9), 5.45 (br q,
J=6.7 Hz, H-1), 5.35 (td, 7.4, 11.2 Hz, H-4), 4.98 (br
q, J=9.0 Hz, H8), 3.29 (d, J=7.1 Hz, H5, H5%), 3.05
(dd, J=10.4, 16.9 Hz, H7), 2.69 (dd, J=8.9, 16.8 Hz,
H7%), 1.76 (d and s, Me-1 and Me-2), 1.68 (d, J=6.7
.