Reaction of trisubstituted alkenes with iron porphyrin carbenes: Facile synthesis of tetrasubstituted dienes and cyclopentadienes

Article abstract of DOI:10.1039/c3cc44092c

The unprecedented reaction of trisubstituted alkenes with iron porphyrin carbenes has been successfully developed. Both multiply substituted 1,3-butadiene and cyclopentadiene products are readily accessible with high efficiency and selectivity in good yields.

Full text of DOI:10.1039/c3cc44092c

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Reaction of trisubstituted alkenes with iron porphyrin
carbenes: facile synthesis of tetrasubstituted dienes
and cyclopentadienes†
Cite this: Chem. Commun., 2013,
49, 7436
Received 31st May 2013,
Accepted 22nd June 2013
Peng Wang, Saihu Liao, Sunewang R. Wang, Run-Duo Gao and Yong Tang*
DOI: 10.1039/c3cc44092c
www.rsc.org/chemcomm
The unprecedented reaction of trisubstituted alkenes with iron
porphyrin carbenes has been successfully developed. Both multiply
substituted 1,3-butadiene and cyclopentadiene products are readily
accessible with high efficiency and selectivity in good yields.
Scheme 1 Iron mediated reactions of ylide-activated trisubstituted alkenes.
Table 1 Substituted group effects on the cyclopropanation/ring-opening reaction
Reactions of metal carbenes/carbenoids with alkenes are a type of
fundamental transformation in organic chemistry.1,2 However, the
reaction type, reactivity and selectivity of these transformations
strongly depend on the properties of the metal carbenes (carbenoids)
and the alkenes.1,2 Accordingly, in contrast to the great success
achieved with terminal olefins,1–3 the reactions of electron-deficient
alkenes and sterically hindered olefins are far less reported.4 For
example, iron-porphyrins have proved to be a type of powerful
catalysts for the cyclopropanation of terminal alkenes, but they are
inactive toward a,b-unsaturated carbonyl compounds and tri- or
tetra-substituted alkenes.5 This could be ascribed to the electrophilic
nature of iron carbenes and their strict shape selectivity. Recently, we
realized a formal sp2 C–H insertion reaction of crotonate-derived
a,b-unsaturated esters with Fe-carbenes via cyclopropanation/ring-
opening by introducing an ylide group to improve the electron
density of the double bond.6,7 This result suggests that the electronic
nature of the substrates might be the main cause of their low
Entrya
R
Yieldb (%)
(3E, 5E)/(3E, 5Z)c
1
2
MeO2C-(1a)
Ph-(1b)
ND
ND
—
—
3
Me-(1c)
MeO-(1d)
MeO-(1d)
13 (3a)
49 (4a)
NR
69/31
83/17
—
4
5d
a
Phosphonium salt 1 (0.5 mmol), LiHMDS (0.6 mL, 1.0 M in THF,
0.6 mmol), MDA (50 mL, 0.6 mmol), PCBA (56 mg, 0.4 mmol), Fe(TCP)Cl
b
c
(1.7 mg, 0.002 mmol), PhCH3 (4.0 mL). Isolated yield. Determined
by 1H NMR. Without LiHMDS.
d
reactivity in the case of a,b-unsaturated esters.7 Inspired by this methyl diazo acetate (MDA) in the presence of a catalytic amount of
success, we became curious about whether this strategy could also tetra(4-chlorophenyl)porphyrin iron chloride (Fe(TCP)Cl) only led to
be employed for the reaction of ‘‘dead’’ trisubstituted alkenes with dimerization of MDA and the direct Wittig reaction of 1a–b with
iron carbenes. Herein, we wish to report our effort toward this goal p-chlorobenzaldehyde (entries 1 and 2, Table 1). Increasing the
and the realization of the reactions of trisubstituted alkenes with electron density of the CQC double bond by installing a methyl
iron porphyrin carbenes where both multiply substituted 1,3-buta- group, to our delight, delivered a 13% yield of desired 1,3-butadiene
diene and cyclopentadiene products are accessible with high effi- products with a selectivity of 69 to 31, (3E, 5E)/(3E, 5Z). Upon
ciency and selectivity by using different carbene sources (Scheme 1). replacing the methyl group with a methoxy group, the yield of
Initially, the substituent effect on trisubstituted allylic phospho- 1,3-butadiene derivative 4a was improved to 49% with a better
nium salts 1 was first investigated with LiHMDS as a base. As shown selectivity of 83 to 17 (entry 3 vs. entry 4, Table 1). As expected, this
in Table 1, the reactions of phosphonium salts 1a and 1b with reaction did not work at all in the absence of the base (entry 5, Table 1).
Based on these results, an extensive screening of the reaction
conditions was conducted next by using phosphonium bromide 1d,
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
MDA and 4-chlorobenzaldehyde (PCBA) in the presence of a
Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China.
catalytic amount of [Fe(TCP)Cl].8 To our delight, the 1,3-butadiene
E-mail: tangy@sioc.ac.cn
products could be obtained in 89% yield with an excellent selec-
tivity (99/1) finally, when using t-BuOK as a base in CH3CN media
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c3cc44092c
c
7436 Chem. Commun., 2013, 49, 7436--7438
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Table 2 Synthesis of tetrasubstituted dienes
Table 3 Synthesis of cyclopentadiene derivatives
Entrya
R1
R2
R3
Yieldb (%)
Entrya
R
t (h)
3E, 5E-4b (%)
3E, 5E/3E, 5Zc
1
2
3
4
5
6
7
8
Me
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Me
Me
Et
t-Bu
Ph
Ph
Ph
Ph
65 (5a)
74 (5b)
76 (5c)
50 (5d)
40 (5e)
45 (5f)
50 (5g)
57 (5h)
48 (5i)
48 (5j)
70 (5k)
1
2
3
4
5
6
7
8
4-ClC6H4–
4-BrC6H4–
6
9
6
6
6
36
31
31
31
32
8
15
24
24
36
89 (4a)
86 (4b)
78 (4c)
83 (4d)
90 (4e)
90 (4f)
71 (4g)
77 (4h)
77 (4i)
55 (4j)
95 (4k)
86 (4l)
64 (4m)
72 (4n)
49 (4o)
99/1
96/4
97/3
97/3
97/3
95/5
99/1
97/3
97/3
98/2
97/3
96/4
97/3
92/8
95/5
2-NO2C6H4–
3-NO2C6H4–
4-NO2C6H4–
C6H5–
2-CH3C6H4–
3-CH3C6H4–
4-CH3C6H4–
4-CH3OC6H4–
2,4-Cl2C6H3–
1-Naphthyl–
E-PhCHQCH–
PhC2H4–
CH2QCHCH2CH2
Ph
Et
Et
Et
Et
Et
Et
Et
Et
p-CH3OC6H4
p-CH3C6H4
p-FC6H4
p-ClC6H4
p-BrC6H4
m-BrC6H4
9
9
10
11
12
13
10
11
12
13
14
15
E-PhCHQCH
2-Furyl
46 (5l)
73 (5m)
a
Conditions: ylide 2 (0.4 mmol), R3COCHN2 (0.56 mmol), Fe(TCP)Cl
n-Octyl–
b
(1.7 mg, 0.002 mmol), DCE (4.0 mL), 20 1C. Isolated yield.
a
Phosphonium salt 1d (235.5 mg, 0.5 mmol), tBuOK (67.2 mg,
0.6 mmol), MDA (50 mL, 0.6 mmol), aldehyde (0.4 mmol), Fe(TCP)Cl
b
(1.7 mg, 0.002 mmol), CH3CN (4.0 mL). Isolated yield of the single
conditions, and the results are presented in Table 3. Replacement of
the ethoxy group with a methoxy group decreased the yield to 65%
(entry 1, Table 3). On the other hand, bulky tert-butyl ester gave a
lower yield than methyl and ethyl esters (entry 4, Table 3). The
electronic nature of the substituents on diazo arylethanone slightly
influenced the yield (entries 6–10), while the meta bromo-substituted
diazo compound gave a much better yield than the para-substituted
one (entries 10 and 11). However, no desired product was observed
when 1-(2-bromophenyl)-2-diazoethanone was employed. When
(E)-1-diazo-4-phenylbut-3-en-2-one and 2-diazo-1-(furan-2-yl) ethanone
were employed, the desired products were obtained in 46% and 73%
yield respectively (entries 12 and 13, Table 3).
isomer. Determined by 1H NMR.
c
(entry 1, Table 2). Notably, the catalyst loading can be further
lowered to 0.1 mol% without apparent reduction of the catalytic
efficiency (Table S1 in the ESI†). The successful activation of the
trisubstituted CQC double bond by introducing two electron-
donating groups (the ylidic and methoxy groups) suggests that the
steric factor in the metal carbene-involved reactions could be over-
come, at least partially, by increasing the electron density of the
CQC double bond.
Under the optimized conditions, a series of aldehydes bearing
aryl and aliphatic groups was examined. As shown in Table 2, the
corresponding 1,3-butadienes (3E, 5E)-4 can be obtained generally
in high yields with excellent selectivities (entries 1–10). Different
substituted aryl aldehydes provided the desired products with a
similar selectivity (entries 3–6, and entries 7–9, Table 2). Compared
with the sterically hindered ortho-substituted aryl aldehydes, an
apparent increase in yield was observed in the reactions of para-
or meta-substituted aryl aldehydes (entry 3 vs. entries 4 and 5, entry 7
vs. entries 8 and 9, Table 2). On the other hand, electron-rich aryl
aldehydes were converted generally in lower yields, compared with
the electron-deficient ones. To our delight, aliphatic aldehydes are
also suitable substrates, although the selectivity and yield were
slightly lower under the same conditions (entries 14 and 15,
Table 2). Notably, in all cases excellent (E,E)-selectivities were
observed (up to 99 : 1) and only (3E, 5E)-4 was isolated using column
chromatography. The configuration of the product (3E, 5E)-4e was
further confirmed by X-ray analysis (for details, see the ESI†).8
Interestingly, when using 2-diazo-1-phenylethanone in place of
methyl diazoacetate in DCM, cyclopentadiene derivative 5a9 was
isolated in 9% yield. After further optimization of the reaction
parameters such as reaction time, base, solvent etc., we were pleased
to find that the yield of the desired cyclopentadiene derivative 5c can
be improved to 76% in the reaction of ethyl ester 2c with 1.4
equivalents of 2-diazo-1-phenylethanone and 1,1-dichloroethane
(DCE) as the solvent.8 The generality of this formal C–H insertion–
Wittig cascade reaction was further investigated under the optimized
The cyclopentadiene derivatives are valuable intermediates in
organic synthesis,10 and by treatment with hydrochloric acid cyclo-
pentadienes can be readily transformed to cyclopentenones which
are also a useful type of synthetic intermediate as exemplified with
5c (Scheme 2).
A plausible mechanism for the formal sp2 C–H insertion of
trisubstituted allylic phosphorus ylide is proposed in Scheme 3. Cyclo-
propanation of trisubstituted allylic phosphorus ylide affords highly
active cyclopropylmethyl ylide intermediate 7. The ylide- or MeO-group
triggered ring-opening reaction affords a Z–E mixture of 8, which can be
further transformed to tetrasubstituted dienes by trapping with alde-
hydes. According to the configuration of 1,3-butadienes, E-8 should be
the major isomer in this process, but can isomerise to Z-8, which then
undergoes an intramolecular Wittig reaction to afford cyclopentadienes
5 when diazo arylethanones are employed.
Unfortunately, many efforts to trap the cyclopropanation inter-
mediates ended with a failure. Using deuterium labelled diazo
methyl acetate (d3-MDA), deuterium was detected in both methoxy-
carbonyl groups (Scheme 4), which indicates that cyclopropanation
should occur. The different contributions of deuterium in different
Scheme 2 Transformation of cyclopentadiene 5c to cyclopentenone 6.
Chem. Commun., 2013, 49, 7436--7438 7437
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methoxycarbonyl groups may be caused by the diastereoselectivity in
the cyclopropanation step or the different trigger group governed
ring-opening (MeO– vs. Ph3PQCH–), but further mechanistic studies
are needed to draw an explicit rationalization for the current reaction.
In summary, a carbene transfer reaction of tri-substituted
alkenes mediated by iron-porphyrin catalysis has been successfully
realized based on an ylidic activation approach. The reaction with
diazo acetate proceeded via a formal sp2 C–H insertion to the
double bond and delivered multiply substituted 1,3-butadiene
derivatives in moderate to excellent yields with excellent Z–E
selectivity, while utilization of diazo arylethanone as the substrate
allows an efficient construction of cyclopentadiene derivatives. To
our knowledge, this reaction represents the first example of the
reactions of trisubstituted a,b-unsaturated carbonyl esters with iron
carbenes. The current reaction further demonstrated that the low
reactivity or inactivity of di- and tri-substituted alkenes toward
electrophilic iron carbenes could be partially overcome by increasing
the electron density of the double bond.
We are grateful for the financial support from the Natural
Science Foundation of China (No. 20932008, 21121062, 21272248),
the Major State Basic Research Development Program (Grant No.
2009CB825300) and Chinese Academy of Sciences.
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c
7438 Chem. Commun., 2013, 49, 7436--7438
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