Reactions of iron carbenes with α,β-unsaturated esters by using an umpolung approach: Mechanism and applications

Article abstract of DOI:10.1002/chem.201204182

An Umpolung approach, in which a phosphorus ylide moiety was introduced to increase the electron density of the double bond, was developed to activate electron-deficient alkenes for reaction with electrophilic iron carbenes. In tandem with the Wittig reaction, the reactions of α,β-unsaturated esters with in situ generated Fe-carbene complexes delivered formal C-H insertion products through cyclopropanation/ring-opening reactions. DFT calculations and cross-experiments indicate that, in this process, the ring opening of the cyclopropylmethyl ylide intermediate is rapid and reversible and the subsequent proton transfer is the rate-determining step. Further studies revealed that, based on the choice of the ylide and ester groups, as well as the base, the reaction could be steered towards either the ring-opening pathway or to the production of vinyl cyclopropanes. Copyright

Full text of DOI:10.1002/chem.201204182

DOI: 10.1002/chem.201204182
Reactions of Iron Carbenes with a,b-Unsaturated Esters by Using an
Umpolung Approach: Mechanism and Applications
Peng Wang, Lin Ling, Sai-Hu Liao, Jian-Bo Zhu, Sunewang R. Wang, Yu-Xue Li,* and
Yong Tang*[a]
À
Abstract: An Umpolung approach, in
which a phosphorus ylide moiety was
introduced to increase the electron
density of the double bond, was devel-
oped to activate electron-deficient al-
kenes for reaction with electrophilic
iron carbenes. In tandem with the
Wittig reaction, the reactions of a,b-
unsaturated esters with in situ generat-
formal C H insertion products through
methyl ylide intermediate is rapid and
reversible and the subsequent proton
transfer is the rate-determining step.
Further studies revealed that, based on
the choice of the ylide and ester
groups, as well as the base, the reaction
could be steered towards either the
ring-opening pathway or to the produc-
tion of vinyl cyclopropanes.
cyclopropanation/ring-opening
reac-
tions. DFT calculations and cross-ex-
periments indicate that, in this process,
the ring opening of the cyclopropyl-
Keywords: carbenes · cyclopropa-
nation · iron · Umpolung reaction ·
ylides
À
ed Fe carbene complexes delivered
Introduction
successful example[5] reported so far is probably the radical
À
cobalt porphyrin system reported by Zhang and co-work-
Transition-metal-catalyzed carbene transfer from diazo com-
pounds to olefins is a useful and important type of transfor-
mation in organic synthesis.[1,2] However, aside from the
properties of the metal carbenes or carbenoids, the reaction
type, reactivity, and the regio- and stereoselectivity of the
transfer are usually heavily influenced by the electronic
nature of the alkene, steric hindrance, and the adjacent
functionality.[1–3] For example, in the cyclopropanation reac-
tion, great success has been achieved with electron-rich and
terminal olefins.[1,4] However, electron-deficient alkenes,
such as a,b-unsaturated carbonyl compounds, and sterically
hindered olefins, such as 1,2-disubstituted, trisubstituted,
and tetrasubstituted olefins, are far less reported, owing to
the electrophilic nature and structural sensitivity of most
ers.[6] We recently introduced an Umpolung activation ap-
À
proach for electron-deficient alkenes, in which the iron por-
phyrin complex catalyzed carbene transfer to a,b-unsaturat-
À
ed esters and produced unusual formal Csp2 H insertion
products through a cyclopropanation/ring-opening process.[7]
Herein, we report this reaction and a mechanistic study in
detail, together with an extension of this Umpolung method
to a tandem cyclopropanation/Wittig reaction.
Results and Discussion
À
Fe porphyrin complexes have shown excellent stability and
efficiency in the cyclopropanation reactions of alkenes[8] and
they have even been employed under aqueous and strongly
basic conditions,[8a–d] thus suggesting their high potential for
metal carbene intermediates.[1–3]To realize the reaction of
À
electron-deficient alkenes with metal carbenes (carbenoids),
extensive studies have been performed, but with quite limit-
ed success. To the best of our knowledge, only a few direct
catalytic carbene-transfer reactions for the cyclopropanation
of electron-poor alkenes have been reported and large
amounts of excess olefin are always employed.[4] The most
À
practical use. However, Fe porphyrin-derived carbenes are
strongly electrophilic and inactive toward electron-deficient
olefins, such as methyl crotonate.[9] Although both steric hin-
drance and electron deficiency are possible reasons for this
inactivity, we hypothesized that, in the cases of inactive 1,2-
disubstituted alkenes, such as a,b-unsaturated carbonyl
esters, their electronic nature might be the main cause.[10]
Considering that electron-deficient olefins usually contain
an acidic allylic proton, we conceived that deprotonation
with an appropriate base would produce an allylic carbanion
and probably reverse its polarity, thus making the double
bond electron-rich enough to react with electrophilic metal
carbenes (Scheme 1). However, in our initial study, subject-
ing methyl crotonate to basic conditions (with lithium bis-
[a] P. Wang, Dr. L. Ling, Dr. S.-H. Liao, J.-B. Zhu, S. R. Wang,
Prof. Dr. Y.-X. Li, Prof. Dr. Y. Tang
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences
345 Lingling Lu, Shanghai 200032 (P.R. China)
E-mail: liyuxue@sioc.ac.cn
tangy@sioc.ac.cn
AHCTUNGTREG(NNNU trimethylsilyl)amide (LiHMDS) as a base) in the presence
of methyl diazo acetate (MDA) and a catalytic amount of
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201204182.
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FULL PAPER
Scheme 1. Umpolung strategy for the activation of electron-deficient
alkenes.
Scheme 3. Proposed mechanism for the diene formation.
tetra(4-chlorophenyl)porphyrin iron chloride [FeACTHNUGRTNEUNG(TCP)Cl]
led to a dirty reaction, probably owing to the instability or
basicity of the carbanion and to side reactions, such as Mi-
chael reactions, the oligomerization of methyl crotonate, etc.
Thus, we envisioned that the introduction of an electron-ac-
cepting group to stabilize the carbanion could be a potential
solution to our original proposal (Scheme 1).
To further verify this proposed mechanism, cross-experi-
ments by using ylides 2a and 2c with MDA and tert-butyl
diazo acetate (BDA) were performed (Scheme 4, Equa-
During the course of our studies on ylide chemistry,[11] we
+
À
À
recognized that a classical ylide (LnM C RR’) could be re-
garded as a carbanion that contains a unique leaving group.
Thus, the neighboring positively charged group (LnM+)
could be employed as an “electron controller” to stabilize
the carbanion (Scheme 1). Inspired by these structural fea-
tures, we designed crotonate-derived allylic phosphorus
ylide 2a as a model substrate for our investigation. Interest-
ingly, attempts to generate ylide 4a and subsequently trap it
À
with aldehydes delivered the formal Csp2 H insertion prod-
ucts, namely 1,1,4-trisubstituted 1,3-butadienes (5), rather
than their corresponding vinyl cyclopropanes (6;
Scheme 2).[7]
Scheme 4. Cross-experiments.
tions (1) and (2)). In each case, both products 8 and 9 were
obtained in a 1:8.6 ratio (8/9). Similar results were also ob-
served in the corresponding cross-experiments with isoprop-
yl diazo acetate and ylide 2b (Scheme 4, Equations (3) and
(4)). These results indicated that the reaction most likely
proceeded through a tandem cyclopropanation/ring-open-
ing/Wittig process, as proposed in Scheme 3, rather than
Scheme 2. Reaction of ylide 2a with iron carbenoid 3a.
À
through a direct Csp2 H insertion, which should exclusively
lead to compound 8 (10) or 9 (11).[12] Moreover, different
ester groups lead to different product distributions in the
cross-experiments (Scheme 4), thus suggesting that the rela-
tive configurations and/or steric hindrance of the substitu-
ents in the cyclopropylmethyl ylide intermediates might
However, in this reaction, cross-experiments and the suc-
cessful trapping of intermediate 4a suggested that the cyclo-
propanation of crotonate-derived phosphorus ylides did
occur;[7] thus, we proposed a plausible mechanism, as shown
in Scheme 3: The cyclopropanation of ylide 2a by an iron
carbene gives cyclopropylmethyl ylide intermediate 4a,
which then rapidly undergoes an ylide-triggered ring-open-
ing reaction and subsequent proton transfer to afford ylide
7a. Finally, treatment with aldehydes gives the ring-opened
1,3-butadiene products (5).
À
À
affect the relative fission of the C1 C2 versus C1 C3 bonds
in compound 4a (Scheme 3).
To determine the influence of the configuration of the cy-
clopropylmethyl ylide on the product distribution, we pre-
pared salts 12a and 12b with a defined relative configura-
tion that could afford cyclopropylmethyl ylide intermediates
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Y.-X. Li, Y. Tang et al.
upon treatment with a base (Scheme 5). Although diaste-
ACHTUNGTRENNUNGreoisomers 12a and 12b had a different relative configura-
tion, when treated with LiHMDS, 1,3-butadiene 11 was ob-
Theoretical study: DFT calculations were performed with
the Gaussian 03[14] program. The geometries were fully opti-
mized at the B3LYP[15]/6-31G* level of theory; harmonic vi-
bration frequency calculations confirmed that the optimized
structures were either minima (with no imaginary vibra-
tions) or transition states (with one imaginary vibration). To
determine more-accurate energies, single-point energies and
solvent effects were calculated by using the IEFPCM[16]
model (UAHF radii) in THF (e=7.59) at the B3LYP/6-
311+G** level of theory. The final relative free energies
(DGsol, in kcalmolÀ1) were obtained by adding the single-
point energies and the solvent-effect corrections, as well as
the thermal corrections at the B3LYP/6-31G* level. The
phosphinyl PMe3 group was used in the models to accelerate
the calculations. Reaction pathways that proceeded from cy-
clopropylmethyl ylide 4a to intermediate 7a (Scheme 3)
have been studied in detail.[17] These results showed that the
direct intramolecular 1,2-proton transfer was unlikely, owing
to the high energy barrier (30.1 kcalmolÀ1).[17] The most fa-
vorable mechanism was the ylide-self-assisted ring-opening
and intermolecular proton transfer, in which the assisting
ylide acted as a proton shuttle.
Scheme 5. Compounds 12a and 12b as probes to study the selectivity in
the ring-opening step.
tained as the major isomer in both cases and with the same
ratio of compounds 10/11 (Scheme 5), thus indicating that
the configuration of compound 4a had a negligible effect on
the product distribution, whereas the steric hindrance of the
substituents on the cyclopropylmethyl ylide could be the
cause. To further understand the reaction mechanism and, in
particular, to gain insight into the selectivity of the ring-
opening step and the factors that influence the product dis-
tribution, density functional theory (DFT)[13] calculations
were performed.
As shown in Scheme 6, structure 4a-Y contains two mole-
cules of ylide 4a. Surprisingly, the ring-opening step occurs
very easily, with a small barrier of 0.8 kcalmolÀ1, thus lead-
ing to a relatively stable intermediate, Int1-Y (À1.3 kcal
molÀ1). After a conformational change with rotation of the
À1
À
C1 C2 bond (TS-Rot-Y, 9.0 kcalmol ), proton abstraction
from the C2 position in Int2-Y occurs via transition state
Scheme 6. Calculated reaction pathways in the self-assisted mechanism for ylide 4a (in some structures, the assisting ylide is omitted for clarity).
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Reactions of Iron Carbenes with a,b-Unsaturated Esters
FULL PAPER
TS-PT1-Y (13.8 kcalmolÀ1), thus leading to intermediate
Int3-Y. Subsequently, protonation at the C3 position in Int3-
Y (TS-PT2-Y, À6.7 kcalmolÀ1) fulfills a formal 1,2 proton
transfer and leads to intermediate 7a-Y, which can be trap-
ped by aldehydes to give 1,3-butadiene derivatives. Direct
proton abstraction from the C2 position in Int1-Y by the
cyclopropylmethyl ylide is less favorable (TS-PT1’-Y,
17.4 kcalmolÀ1).
1.0 kcalmolÀ1 more favorable than TS-PT-Y-tBu, thus sug-
gesting that the abstraction of a proton from TS-PT-Y-Me is
much easier than from TS-PT-Y-tBu, owing to the steric hin-
drance of the phosphonium moiety and the tert-butyl group.
Thus, the ring opening mainly proceeds on the side of the
À
methyl ester (fission of the C1 C2 bond), rather than on the
side of the tert-butyl ester. This result is consistent with the
experimental observations, thus explaining the steric effect
of the ester on the product distribution.
The calculated results given in Scheme 6 show that the
ring-opening process is very fast and reversible. In structure
À
À
4a-Y, the C1 C2 and C1 C3 bond lengths are 1.536 ꢁ and
Construction of vinylcyclopropanes through the catalytic cy-
clopropanation of allylic phosphonium compounds: In light
of the calculated mechanism that the cyclopropylmethyl
ylide intermediate itself can act as a base to promote the
proton transfer and accelerate the ring-opening reaction, we
envisioned that the best way to efficiently trap intermediate
4a for the formation of the cyclopropane might be to keep
it at a lower concentration than the trapping aldehyde.
Taking notice of the stability of phosphonium salt 13a,[7] we
proposed that salt 13a could be employed as a “reservoir”
of the corresponding ylide (4a). Based on this concept, a
new strategy is shown in Scheme 7. In this strategy, the ylide
À
1.546 ꢁ, respectively, longer than the C2 C3 bond
(1.523 ꢁ). Clearly, it is the electron-donating ylidic carban-
ion and the electron-withdrawing ester groups that make
the cyclopropane highly polarized, thus facilitating the ring-
opening step. Based on the calculated results, proton trans-
fer from Int2-Y to Int3-Y is the rate-determining step and is
irreversible under the reaction conditions. Therefore, the
distribution of the ring-opened products in cross-experi-
ments is governed by transition state TS-PT1-Y.
To gain more insight into the ester effect, by which the cy-
clopropane always opens from the side of the less-hindered
ester group (Scheme 4 and Scheme 5), calculations were per-
formed for the self-assisted proton-transfer reaction of ylide
4b. Considering the orientation of the phosphorus group
and the ester groups, a conformational search was per-
formed for transition states that corresponded to ring open-
ing from the MeO (TS-PT-Y-Me) and tBuO sides (TS-PT-Y-
tBu) and eight structures were calculated.[14] As shown in
Figure 1, the most-stable transition state, TS-PT-Y-Me, was
Scheme 7. Strategy for the cyclopropanation of allylide.
that is formed (4a) in situ through cyclopropanation will be
quickly protonated by allylic phosphonium bromide 1aa and
is “stored” in the form of salt 13a because compound 4a is
a stronger base than compound 2a. Therefore, the ring
opening of ylide 4a would be effectively suppressed, where-
as it can be released in a steerable way through an acid/base
equilibrium reaction by a suitable base and, thus, maintain
the relative concentration of compound 4a to the aldehyde
at a low (but productive) level.
To test this hypothesis, the cyclopropanation of allylic
phosphonium salt 1aa with methyl diazo acetate was per-
formed in the presence of a catalytic amount of [FeACTHNUGRTNEUNG(TCP)Cl]
and ylide 2a as an initiator. Gratifyingly, phosphonium salts
13a and 14a were obtained in 35% yield, in a ratio of 81:19,
as determined by 31P NMR spectroscopy in CDCl3 (Table 1,
entry 2). Ylide 7a could also initiate this reaction, thus
giving similar results (Table 1, entry 3). In a control experi-
Figure 1. Ester effect in the self-assisted proton-transfer reaction of ylide
4b.
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Y.-X. Li, Y. Tang et al.
Table 1. Iron-catalyzed cyclopropanation of phosphonium salt 1aa.
impede the proton transfer and, thus, afford a more-efficient
trapping of the cyclopropylmethyl ylide.
Based on these findings, further optimization of the one-
pot reaction conditions was conducted by using tert-butyl-
crotonate-derived phosphonium salt 1ca, tert-butyl diazo
acetate (BDA), and 4-chlorobenzaldehyde (PCBA) in the
presence of a catalytic amount of [FeACTHNUTRGNEUNG(TCP)Cl]. Finally, the
Entry
Initiator [mol%]
Solvent
Yield [%][a]
13a/14a[a,b]
ratio of compounds 17a/18a was improved to 94:6, with an
88% yield of compound 17a when mixed solvent system
1,2-dimethoxyethane (DME)/PhCl (1:4, v/v) was used
(Table 2, entry 1),[17] and the reaction scope was examined.
As shown in Table 2, good-to-excellent yields of the desired
vinylcyclopropanes (17) were obtained with moderate-to-
good Z selectivities in the reactions of aromatic aldehydes.
Notably, the selectivity (17 versus 18) was strongly depend-
ent on the reactivity of the aldehyde, as well as on the sub-
stituents on the aromatic ring. In general, vinylcyclopro-
panes 17 were obtained with good-to-excellent selectivities
when activated benzaldehydes that contained electron-with-
drawing groups, such as halo, nitro, trifluoromethyl, and
cyano group on the benzene ring, were used (Table 2, en-
tries 1–10). This trend correlated well with the efficiency of
trapping the cyclopropylmethyl ylide intermediate in the
Wittig step, which heavily relied on the reactivity of the al-
dehyde. Lower selectivities for compound 17 were obtained
with benzaldehyde and electron-rich benzaldehydes
1
2
–
THF
THF
THF
CH2Cl2
CH2Cl2
CH2Cl2
n.d.
35
48
99
99
–
2a (10)
7a (10)
2a (10)
2a (2)
81:19
78:22
67:33
59:41
59:41
3[c]
4
5
6[d]
K2CO3 (10)
99
[a] Determined by 31P NMR spectroscopy; n.d.=not determined. [b] The
E/Z ratio of compound 14a was 85:15, as determined by 31P NMR spec-
troscopy. [c] Compound 7a was synthesized in situ according to the pro-
cedure in Ref. [5]. [d] [FeACHTUNTGRNEUNG(TCP)Cl] and MDA were added after the mix-
ture of compound 1aa and K2CO3 had been stirred for 10 min at room
temperature.
ment without any basic initiator, no reaction was observed
(Table 1, entry 1).
Salt 1aa was poorly soluble in THF and low conversion
was observed (Table 1, entry 2), whereas phosphonium salt
1aa was completely consumed in CH2Cl2, albeit with slightly
lower selectivity (Table 1, entry 4). Further studies demon-
strated that this strategy was still efficient with 2 mol% of
compound 2a or 10 mol% of K2CO3 (Table 1, entries 5 and
6). Encouraged by these results, a one-pot procedure for the
synthesis of vinylcyclopropanes was attempted by employing
K2CO3 as the base and 4-chlorobenzaldehyde (PCBA) as
the trapping agent (Scheme 8). With compound 1aa, cinna-
mylcyclopropanes 6a was isolated in 22% yield with a selec-
tivity of 30:70 (6a/5a). To our delight, replacement of
methyl groups by tert-butyl groups on both the crotonate
and the diazo acetate improved the yield of cinnamylcyclo-
propane (17a) to 65%, together with much higher selectivi-
ty (17a/18a, 74:26). These results are consistent with the cal-
culations, which showed that a bulky ester group could
Table 2. Synthesis of vinylcyclopropanes through the catalytic cyclopro-
panation of crotonate-derived phosphonium salts.[a]
Entry
R
t [h]
17/18[b]
17 [%][c]
Z/E (17)[b]
1
2
3
4
5
6
7
8
4-ClC6H4
3-ClC6H4
2-ClC6H4
7
7
7
7
7
7
10
7
10
7
7
18
36
22
24
7
94:6
90:10
90:10
95:5
95:5
87:13
94:6
93:7
94:6
94:6
71:29
58:42
–
88 (17a)
87 (17b)
76 (17c)
79 (17d)
87 (17e)
73 (17 f)
94 (17g)
90 (17h)
93 (17i)
88 (17j)
57 (17k)
57 (17l)
82:18
82:18
66:34
75:25
79:21
55:45
79:21
81:19
79:21
46:54
86:14
88:12
–
4-NO2C6H4
3-NO2C6H4
2-NO2C6H4
4-CNC6H4
4-BrC6H4
4-CF3C6H4
2,4-Cl2C6H3
C6H5
4-CH3C6H4
4-CH3OC6H4
(E)-PhCH=CH
CO2Et
9
10
11
12
13[d]
14
15
16[e]
[f]
–
65:35
–
<1:99
63 (17m)
81 (17n)
– (17o)
77:23
48:52
–
2-HOC6H4
[a] Reaction conditions: Phosphonium salt 1ca (289.8 mg, 0.60 mmol),
K2CO3 (99.4 mg, 0.72 mmol), [Fe(TCP)Cl] (1.7 mg, 0.002 mmol), BDA
AHCTUNGTRENNUNG
(152 mL, 1.2 mmol), aldehyde (0.4 mmol), DME/PhCl (1:4 v/v, 4.0 mL),
208C. For detailed procedures, see the Supporting Information. [b] Deter-
1
mined by H NMR spectroscopy. [c] Yield of isolated product. [d] A com-
plicated mixture was obtained and the yield of the cyclopropane was less
than 17% by 1H NMR analysis of the mixture after isolation. [e] Under
the general cyclopropanation conditions: 91% yield (18o), 18o/17o>
99:1. [f] A complicated mixture of products was obtained.
Scheme 8. Effect of the ester groups on the reaction selectivity.
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Reactions of Iron Carbenes with a,b-Unsaturated Esters
FULL PAPER
(Table 2, entries 11–13), whereas highly reactive ethyl glyox-
alate afforded the desired product (17n) in excellent yield
(Table 2, entry 14). On the other hand, steric effects were
also found to play an important role in determining the
Z selectivity of the vinylcyclopropanes (17). In comparison
with the meta- or para-substituted substrates, a dramatic
drop in the Z selectivity was observed in the reactions of
ortho-substituted compounds (Table 2, entries 3, 6, and 10).
As revealed by the calculations, proton transfer was the
rate-limiting step in the cyclopropane ring-opening process
and the presence of an active hydrogen source would proba-
bly accelerate the proton transfer and increase the diene for-
mation. The case of salicylaldehyde provides a good support
to this fact: Diene 18o was obtained as the sole product in
this reaction and no cyclopropane (17o) was detected by
1H NMR analysis (Table 2, entry 16). The exclusive forma-
tion of diene 18o could be ascribed to the presence of the
ortho-acidic phenolic proton, which may have sped up the
proton transfer and, thus, switch the reaction to the ring-
opening/Wittig pathway to afford the diene products. In
fact, protic solvents, such as tBuOH and iPrOH, were also
found to favor the diene-formation process.
Scheme 10. Cross-experiments under the cyclopropanation conditions.
tron-accepting ability of the phosphonium group should also
affect the proton-transfer step and vary the selectivity be-
tween the cyclopropanation products and the diene prod-
ucts. As shown in Scheme 11, a dramatic change in the reac-
Because the 1H NMR spectra of the obtained cyclopro-
panes indicated the presence of two isomers, oxidative
cleavage and hydrogenation of the double bond were sepa-
rately performed on vinylcyclopropane 17j to determine the
reason for the isomerization (Scheme 9). In both transfor-
Scheme 11. Selectivity for vinylcyclopropanes and 1,3-butadienes with
different phosphines.
tion selectivity (17a versus 18a) was found when the tri-
phenyl phosphine was replaced by tricyclohexyl phosphine
or tri-n-butyl phosphine. In the cases of trialkyl-phosphine-
derived phosphonium salts (1cb and 1cc), only 1,1,4-trisub-
stituted 1,3-butadiene 18a was observed, in stark contrast to
the predominant formation of vinylcyclopropanes in the re-
action of salt 1ca. These results also demonstrated the high
tunability of this reaction, which provides a simple way to
selectively synthesize disubstituted vinylcyclopropanes and
1,3-butadienes. Upon further optimization, the yield of
1,1,4-trisubstituted 1,3-butadiene 18a was improved to 96%,
together with high selectivity, by using tricyclohexyl-phos-
phine-derived phosphonium salt 1cb and tBuOK as a base
(Table 3, entry 1). As shown in Table 3, various aromatic
and aliphatic aldehydes worked well under these conditions,
thus providing the desired butadienes in excellent yields and
high selectivities.
Scheme 9. Oxidation and hydrogenation of vinylcyclopropane 17j.
mations, only a single product was obtained (compounds 19
and 20, respectively), thus suggesting that the two isomers
were the Z and E isomers of the double bond, rather than
the diastereoisomers of the cyclopropanes. These results
also indicate excellent diastereoselectivity in the cyclopropa-
nation step.
Because the ring opening of the cyclopropylmethyl ylide
intermediate is rapid and reversible, the cross-experiments
under standard cyclopropanation conditions should lead to
similar diastereoselectivities in the cyclopropanes. As shown
in Scheme 10, the expected ratios of compounds 21/22 were
observed in the two reactions. This result is also in agree-
ment with the calculated mechanistic data.
Conclusion
We have successfully applied an Umpolung approach to ac-
tivate electron-deficient alkenes (a,b-unsaturated esters) for
reaction with electrophilic iron carbenes, thus confirming
Further improvement of the ring-opening process: Accord-
ing to the ring-opening mechanism of this reaction, the elec-
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Y.-X. Li, Y. Tang et al.
Table 3. Synthesis of 1,3-butadienes through the catalytic cyclopropana-
tion/ring-opening reactions of allylic phosphonium salts.[a]
[3] For selected recent examples of the cyclopropanation of olefins, see:
a) J. Li, S.-H. Liao, H. Xiong, Y.-Y. Zhou, X.-L. Sun, Y. Zhang, X.-
G. Zhou, Y. Tang, Angew. Chem. Int. Ed. 2012, 51, 8838; b) R. Sam-
basivan, Z. T. Ball, Angew. Chem. Int. Ed. 2012, 51, 8568; c) J. F.
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Entry
R
t [h]
18 [%][b]
3E,5E/3E,5Z (other)[c]
1
2
3
4
5
6
7
8
4-ClC6H4
4-BrC6H4
4-NO2C6H4
C6H5
4-CH3C6H4
2-furyl
6
6
6
21
21
24
24
36
96 (18a)
92 (18b)
96 (18c)
97 (18d)
95 (18e)
86 (18 f)
97 (18g)
94 (18h)
92:8 (8)
91:9 (9)
95:5 (8)
92:8 (5)
91:9 (7)
86:14 (8)
97:3 (11)
86:14 (10)
(E)-PhCH=CH
n-octyl
[a] Reaction conditions: Phosphonium salt 1cb (300.6 mg, 0.60 mmol),
tBuOK (80.6 mg, 0.72 mmol), [Fe(TCP)Cl] (1.7 mg, 0.002 mmol), BDA
AHCTUNGTRENNUNG
(152 mL, 1.2 mmol), aldehyde (0.4 mmol), PhCH3 (4.0 mL), 208C. For de-
tailed procedures, see the Supporting Information. [b] Yield of isolated
1
product. [c] Determined by H NMR spectroscopy.
that their electronic nature is the main cause of their inactiv-
ity. Our calculations showed that the ring-opening step of
the intermediate cyclopropylmethyl ylide was rapid and re-
versible and that the subsequent proton-transfer step was
the rate-limiting step in the cyclopropane-ring-opening pro-
ACHTUNGTRENNUNGcess; these results were further experimentally supported by
cross-experiments. On the basis of these mechanistic in-
sights, by judicious choice of the carbanion-stabilizing
groups, the esters, and the base, this reaction could be
steered towards either the ring-opening reaction or along
the cyclopropanation reaction pathway. As has already been
demonstrated in the activation of crotonate-derived model
substrates, this Umpolung strategy represents a new ap-
proach to tune the reactivity of electron-deficient alkenes
with metal carbenes. Further extension of this strategy to
other types of substrates and reactions is currently underway
in our laboratory.
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Acknowledgements
We are grateful for the financial support from the National Natural Sci-
ence Foundation of China (21121062, 21272248, and 20932008) and from
the Major State Basic Research Development Program (2009CB825300).
À
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Chem. Eur. J. 2013, 19, 6766 – 6773

Reactions of Iron Carbenes with a,b-Unsaturated Esters
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Received: November 22, 2012
Revised: February 21, 2013
Published online: March 27, 2013
Chem. Eur. J. 2013, 19, 6766 – 6773
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6773