A new and efficient method for the selective olefination of aldehydes with ethyl diazoacetate catalyzed by an iron(II) porphyrin complex

Article abstract of DOI:10.1021/ja016721v

Olefination of aromatic and aliphatic aldehydes with ethyl diazoacetate was achieved in excellent yields with triphenylphosphine and catalytic amounts of iron(II) meso-tetra(p-tolyl)porphyrin. The reaction conditions are mild and the process is efficient and highly selective (>90%) for the synthesis of the trans-olefin isomer. Results of mechanistic studies are discussed. Copyright

Full text of DOI:10.1021/ja016721v

Published on Web 12/14/2001
A New and Efficient Method for the Selective Olefination of Aldehydes with
Ethyl Diazoacetate Catalyzed by an Iron(II) Porphyrin Complex
Gholam A. Mirafzal,‡ Guilong Cheng, and L. Keith Woo*
Department of Chemistry, Iowa State UniVersity, Gilman Hall, Ames, Iowa 50011-3111
Received July 27, 2001; Revised Manuscript Received October 30, 2001
Table 1. Olefination of Aldehydes with EDA/Ph3P/FeII(TTP)a
Transition metal complexes based on porphyrins and on a variety
of ancillary ligands have been used extensively by this group1 and
alde- reaction yield turnover trans/cis alde- reaction yield turnover trans/cis
others2 to catalyze the cyclopropanation of alkenes with ethyl
diazoacetate and other suitable diazo reagents. In this communica-
tion, we describe a novel extension of the catalytic activity of
metalloporphyrins with the first use of an iron(II) porphyrin complex
as a catalyst for the efficient and selective olefination of aldehydes.
The generation of a carbon-carbon double bond is one of the
important synthetic transformations in organic chemistry, especially
in the areas of natural products and polymer synthesis. Although
other metal complexes can catalyze this reaction,3 the iron system
is especially proficient and cost-effective.
Olefination of aromatic and aliphatic aldehydes (Table 1) was
achieved in excellent yield at ambient temperature using 2 equiv
of ethyl diazoacetate, N2CHCO2Et (EDA), and 1.1 equiv of
triphenylphosphine, Ph3P, in the presence of catalytic amounts of
iron(II) meso-tetra(p-tolyl)porphyrin, FeII(TTP) (1-2 mol %), in
toluene (eq 1). Ratios of reagents were selected for convenient
reaction times, high yields, and ease of purification. Ethyl maleate
and fumarate were also observed as side products, but were readily
hyde time (h) (%)b
no.
selectivityc hyde time (h) (%)b
no.
selectivityc
1
2
3
6
12
3
94
99
95
128
119
98
24:1
24:1
13:1
4
5
6
2
23
12
90
85
93
80
95
64
24:1
10:1
49:1
a Typical procedure: To a stirred solution of 1-2 mol % FeII(TTP),
0.94 mmol (1 equiv) aldehyde, and 1.04 mmol (1.1 equiv) of Ph3P in 10
mL of toluene at ambient temperature under an inert atmosphere was added
dropwise a solution of 1.88 mmol (2 equiv) of EDA in 3 mL of toluene.
The progress of reaction was monitored by GC. b Isolated yield. c Trans/
cis selectivity was determined by GC and 1H NMR. In our GC analysis,
the cis isomer appeared at a shorter retention time versus the trans isomer.
3
1H NMR analysis showed a JHH of 15.9 Hz for trans-hydrogens and a
3JHH of 12.6 Hz for cis-hydrogens.
Scheme 1
FeII
RCHO + N2CHCO2Et + Ph3P (TTP)8 RCHdCHCO2Et + Ph3PdO (1)
for the analogous methyltrioxorhenium (MTO) catalyzed reaction3e,5
involves oxygen atom abstraction from MTO by phosphine. The
resultant Re(V) dioxo complex reacts with a diazo reagent to
produce a carbene complex that subsequently forms a metalla-
oxetane species in the presence of aldehydes. Fragmentation of the
metallaoxetane produces the new olefin and regenerates MTO. We
presume that the active species in the iron porphyrin catalyzed
reactions is an iron-carbene complex formed by reaction of the
iron(II) porphyrin with EDA. Related complexes prepared from
mesityl diazomethane and trimethylsilyl diazomethane are readily
observed by 1H NMR spectroscopy.1c,d However, (TTP)Fed
CHCO2Et is too reactive to isolate or detect spectroscopically. The
more electron rich osmium analogue, (TTP)OsdCHCO2Et, has been
isolated and is well characterized.1a,b If a metallaoxetane intermedi-
ate is involved, the iron-carbene complex may serve as a
nucleophile6 that attacks the carbonyl functional group of aldehydes.
This is consistent with the higher reactivity of electron poor
aldehydes (vide infra). Subsequent ring opening of the metalla-
oxetane would produce an olefin and an oxoiron porphyrin complex.
Regeneration of Fe(TTP) would occur by oxidation of phosphine
to phosphine oxide.
-N2
R ) Ph-, p-CH3C6H4-, p-NO2C6H4-, p-ClC6H4-, PhCH2-, (Ph)2CH-
removed by chromatography. Treatment of benzaldehyde, 1, with
EDA/Ph3P/FeII(TTP) in toluene at ambient temperature resulted in
98% conversion to ethyl cinnamate after 6 h of reaction time. Both
GC and 1H NMR analysis confirmed a high selectivity for trans to
cis olefin products (24:1).4 Purification of the trans-olefin product
by silica gel column chromatography with hexane:ethyl acetate
(20:1 v/v) afforded a 94% yield for olefination of 1 (Table 1). The
reaction is catalytic as no olefination products were formed without
FeII(TTP). In the absence of the catalyst, the azine, PhCHdN-
NdCHCO2Et (m/z 204, 131(base), 104, 77), was produced when
the reaction mixture was allowed to stir for a period of 2 days.
The reaction in the absence of Ph3P also produced no olefination
product. We found that this reaction requires a stoichiometric
amount of Ph3P to that of the aldehydes to give a high conversion
to olefination products. The aldehyde oxygen is transferred to Ph3P,
producing 1 equiv of phosphine oxide. GC and GC-MS analysis
confirmed formation of Ph3PdO (m/z 278).
For this mechanism to be viable, the inner sphere reaction
between unencumbered oxoiron(IV) and iron(II) porphyrins, pro-
ducing a µ-oxo Fe(III) dimer,7 must be minimal. Formation of the
Fe(III) dimer would serve to quickly inactivate the catalyst.
However, rapid deactivation was not observed8 and attempts were
made to test for the presence of the iron(IV) oxo complex with
other oxygen atom acceptors. Olefins were chosen since oxoiron(IV)
porphyrin complexes effectively epoxidize the double bond.9 When
an Fe(TTP)-catalyzed reaction of benzaldehyde and EDA was run
Preliminary studies were undertaken to probe the mechanism
for this olefination process. A catalytic cycle (Scheme 1) proposed
‡ Associate Professor of Chemistry, Drake University, Des Moines, Iowa.
9
176 VOL. 124, NO. 2, 2002 J. AM. CHEM. SOC.
10.1021/ja016721v CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
with styrene substituted as the reductant in place of Ph3P, no ethyl
cinnamate was observed. The only product was ethyl 2-phenyl-
cyclopropylcarboxylate (100%), indicating that styrene was much
more efficient in reacting with the carbene complex than was the
aldehyde. An alternative oxygen atom acceptor, cyclohexene, was
subsequently employed. 1,2-Substituted olefins are poor cyclopro-
panation substrates,1c but readily undergo epoxidation.9 However,
using cyclohexene in place of Ph3P under catalytic conditions
resulted in neither olefination of the aldehyde nor epoxidation of
the alkene. The organic products were ethyl maleate and fumarate
produced by carbene dimerization. These studies indicated that an
iron-carbene complex was involved but that the oxoiron(IV)
species was an unlikely intermediate.
The reactivity profile of the Fe(TTP)-catalyzed olefination
reaction differs significantly from the MoO(S2CNEt2)2-mediated
process.3h The catalytic cycle for the Mo system purportedly
involves metalloazines,10 (Et2NCS2)2OModN-NdCHCO2Et, and
phosphazines, Ph3PdN-NdCHCO2Et.3h The phosphazine is pre-
sumably responsible for the formation of large amounts of azines
with electron-poor aldehydes in this system.
We also examined two aliphatic aldehyde substrates, phenyl-
acetaldehyde, 5, and diphenylacetaldehyde, 6. Olefination of 5 was
slow and required 23 h of reaction time for a 91% conversion and
85% isolated yield after purification. A high trans to cis selectivity
(10:1) was also achieved for olefination of 5. Olefination of aliphatic
aldehyde, 6, resulted in 95% conversion after 12 h and produced a
trans to cis selectivity of 49:1. Purification of the reaction mixture
from substrate 6 with column chromatography afforded a 93%
isolated yield of the trans-olefin product.
We have reported here the first application of an Fe(II)
metalloporphyrin catalyst for the olefination of carbonyl compounds
with EDA and Ph3P. Both aromatic and aliphatic aldehydes were
efficiently converted to olefin products in excellent yields (>85%)
with high selectivity for the trans-olefin isomer (>90%). Further
mechanistic studies, application of Fe(II) porphyrin complexes as
a catalyst for the olefination of ketones, and the use of other diazo
reagents in this system are currently under investigation.
Acknowledgment. This research was supported by the Research
Corporation and Iowa State University (SPRIG Award). G.A.M.
appreciates support from Drake University for a sabbatical leave.
On the basis of the above data, the most likely mechanism for
the Fe(TTP) olefination reaction is shown in Scheme 2. In this proc-
ess, the Fe complex serves to catalytically convert the diazo reagent
and phosphine to phosphorane. The phosphorane in turn produces
a new olefin and phosphine oxide on reaction with the aldehyde.
Evidence for this mechanism is derived from two key control
experiments. The production of phosphorane, Ph3PdCHCO2Et, was
independently established in a reaction of Ph3P, EDA, and Fe(TTP)
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1
(1 mol %). The phosphorane was clearly identified by H and 31P
NMR spectroscopy.11,12 Particularly diagnostic is the coupling
constant J ) 21 Hz between the phosphorus and the methine pro-
ton.12a In addition, the stoichiometric reaction of Ph3PdCHCO2Et
and benzaldehyde produced ethyl cinnamate in high yields and high
stereoselectivity.
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observed. Qualitatively, the rate of reaction with 2 equiv of Ph3P
was faster than when 1 equiv was used, with no noticeable change
in yields. Above 2 equiv of Ph3P, the rate appeared to saturate.
Scheme 2
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product by silica gel column chromatography gave 99% of the
trans-olefin product (Table 1). The reaction is slower for substrate
2 compared to benzaldehyde due to the presence of the electron-
donating methyl group.
Olefination of p-Cl and p-NO2 substrates, 3 and 4, both
containing electron-withdrawing groups, produced 100% conversion
to olefin in much shorter reaction times. Olefination of 3 was
complete after 3 h and resulted in a trans:cis ratio of 13:1 in 95%
isolated yield after purification. Furthermore, the olefination of 4
was complete after 2 h, producing a high selectivity of trans- to
cis-olefins (24:1) with an isolated yield of 90% after purification.
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Hz, PdCH), 1.19 (3H, t, J ) 7.1 Hz, CH3); transoid isomer: δ 7.47 (m,
C6H5), 7.38 (m, C6H5), 3.78 (2H, q, J ) 7.1 Hz, CH2), 2.76 (1H, d, JP-H
) 21.9 Hz, PdCH), 0.60 (3H, t, J ) 7.1 Hz, CH3). 31P NMR (162 MHz,
CDCl3) cisoid isomer: δ 18.0; transoid isomer: δ 16.6.
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