Rh2(OAc)4-catalyzed 2,3-migration of β-ferrocenecarboxyl α-diazocarbonyl compounds: An efficient synthesis of ferrocene-containing α,β-unsaturated esters

Article abstract of DOI:10.1039/c3ra48071b

A series of β-ferrocenecarboxyl α-diazocarbonyl compounds were prepared by the reaction of ferrocenoyl chloride with β-hydroxyl α-diazocarbonyl compounds in the presence of pyridine. The diazo decomposition of these ferrocene-containing diazocarbonyl compounds with Rh ₂(OAc)₄ resulted in 2,3-ferrocenecarboxyl migration to give ferrocene-containing α,β-unsaturated esters in high yields.

Full text of DOI:10.1039/c3ra48071b

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COMMUNICATION
Rh2(OAc)4-catalyzed 2,3-migration of
b-ferrocenecarboxyl a-diazocarbonyl compounds:
an efficient synthesis of ferrocene-containing
a,b-unsaturated esters†
Cite this: RSC Adv., 2014, 4, 12482
Received 31st December 2013
Accepted 17th February 2014
*
*
Shufeng Chen, Yan Du, Haiying Zhao and Baoguo Li
DOI: 10.1039/c3ra48071b
www.rsc.org/advances
A series of b-ferrocenecarboxyl a-diazocarbonyl compounds were 1,2-migration is sometimes the dominating pathway, which can
prepared by the reaction of ferrocenoyl chloride with b-hydroxyl compete with the typical reactions of diazo compounds, such as
a-diazocarbonyl compounds in the presence of pyridine. The diazo cyclopropanations, X–H (X ¼ C, O, S, N, etc.) insertions and ylide
decomposition of these ferrocene-containing diazocarbonyl formations.6 Among the transition-metal-catalyzed 1,2-migra-
compounds with Rh2(OAc)4 resulted in 2,3-ferrocenecarboxyl migra- tion reactions of a-diazo carbonyl compounds, the 1,2-hydride
tion to give ferrocene-containing a,b-unsaturated esters in high yields. migration is usually predominant,7 but 1,2-aryl, 1,2-alkyl, 1,2-
vinyl, 1,2-acetylenyl and 1,2-thio group migrations are also
reported.8 Besides, 1,2-acetoxy group migration of Rh(II)–car-
bene was also described by Ganem and co-workers in 1981;9 it is
conceived that the 1,2-migration of acetoxy group may proceed
Introduction
through a three-centered or ve-centered transition state, where
the lone pair electrons of the alkoxy or carbonyl oxygen of the
acetoxy group interacts with the electron-decient Rh(II)–car-
bene center (Scheme 1). It should be noted that it is actually a
2,3-migration reaction if 1,2-acetoxy group migration proceeds
through a ve-centered transition state. Wang and co-workers
have demonstrated a 2,3-migration reaction of Rh(II)–carbene
subtly through installation of an amido group onto the b-posi-
tion of the a-diazo carbonyl compounds.10 Inspired by this
report, and also as an extension of our interest in the ferrocene
and diazo chemistry,11 we conceived that an a-diazo carbonyl
compound bearing a ferrocenecarboxyl group on the b-position
may also undergo a similar acyloxy migration in a Rh(II)-cata-
lyzed reaction to give a ferrocene-containing a,b-unsaturated
ester. Moreover, if the reaction occurs as predicted, the
Since its discovery more than sixty years ago, ferrocene has
acquired signicant attention1 as a consequence of its unique
physical and chemical properties which allow for its application
in many areas such as asymmetric catalysis,2 materials science,3
and bioorganometallic chemistry.4 Among these, the eld
where ferrocene importance is continuously increasing is bio-
organometallic chemistry.5 Although ferrocene itself is usually
considered to be a nontoxic, biologically inert compound, many
novel ferrocene derivatives exhibit signicant anticancer, anti-
parasitic, antibacterial, antifungal, and other biological activi-
ties.4,5 Undoubtedly, the design motif and synthesis strategy in
ferrocene-based architectures play the most important role to
deliver the targeted property. Due to their increasing applica-
tions in biology, materials science, and chemistry, there has
been an ever increasing demand for the synthesis of novel
ferrocenes bearing various functional groups through simple
and efficient approaches.
On the other hand, transition-metal-catalyzed diazo
decomposition
of
various
substituted
diazocarbonyl
compounds is a class of important transformation in organic
chemistry that has been widely investigated for its intriguing
mechanistic features and extensive applications in natural
products synthesis.6 In these diazo decomposition reactions,
College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot
010021, China. E-mail: shufengchen@imu.edu.cn; baoguol@sohu.com
† Electronic supplementary information (ESI) available. CCDC 883909. For ESI
and crystallographic data in CIF or other electronic format see DOI:
10.1039/c3ra48071b
Scheme 1 Possible transition state of 1,2-acetoxy migration.
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Table
1
Reaction of b-hydroxy a-diazo esters with ferrocenoyl
migration should proceed through a ve-centered transition
state because of the steric effect of the bulky ferrocene group. In
this paper, we wish to report the Rh2(OAc)4 catalyzed decom-
position of b-ferrocenecarboxyl a-diazocarbonyl compounds.
The results show an efficient 2,3-ferrocenecarboxyl migration
leading to the formation of ferrocene-containing a,b-unsatu-
rated esters.
chloridea
Results and discussion
At the outset of this investigation, we rst converted the
b-hydroxyl group in diazo compound 2 into b-ferrocenecarboxyl
group to afford b-ferrocenecarboxyl substituted diazo
compounds 3a–j (Scheme 2). The b-hydroxy a-diazo esters 2
were prepared by tert-BuOK-catalyzed condensation of ethyl
diazoacetate (EDA) with aldehyde under solvent-free conditions
recently developed by our group with the yields ranging from
69% to 92%.12 Then ferrocenoyl chloride in anhydrous CH2Cl2
was added dropwise to a solution of b-hydroxy a-diazo ester 2
Entry
R
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
2a, C6H5
2
2
2
2.5
1
3
3
1.5
1.5
1.5
3
3a, 56
3b, 55
3c, 57
3d, 70
3e, 65
3f, 66
3g, 61
3h, 70
3i, 60
3j, 50
ndc
2b, p-ClC6H4
2c, p-BrC6H4
2d, o-ClC6H4
2e, p-CH3C6H4
2f, p-NO2C6H4
2g, o-NO2C6H4
2h, H
ꢀ
with pyridine in anhydrous CH2Cl2 at 0 C. The esterication
9
2i, CH3
10
11
12
2j, CH3CH2CH2
2k, p-CH3OC6H4
2l, 2-furyl
reaction was completed within 3 h, and the b-ferrocenecarboxyl
substituted a-diazo carbonyl compounds 3a–j were obtained in
moderate to good yields (Table 1).
3
ndc
a
Reactions were carried out with 1.0 mmol of 2, 1.1 mmol of ferrocenoyl
It is worthwhile to note that the reaction should be quenched
with saturated NaHCO3 at 0 ꢀC in order to avoid the oxidation of
ferrocene as well as the decomposition of the diazo compound
under acidic conditions. Most aromatic or aliphatic substitu-
ents could be tolerated, and the reaction gave moderate to good
yields of the products 3a–j (Table 1, entries 1–10). However,
when R was a p-methoxyphenyl or 2-furyl group, we were
disappointed to nd that the reaction gave a complex mixture
and no desired b-ferrocenecarboxyl substituted a-diazo ester
product was detected (Table 1, entries 11 and 12). Moreover, the
pure ferrocene-containing diazo compounds 3a–j obtained
b
chloride, and 2.0 mmol of pyridine at 0 ꢀC. Yield of isolated product
c
aer chromatography. No b-ferrocenecarboxyl substituted a-diazo
ester product was detected.
substrates with a phenyl ring bearing a strong electron-with-
drawing group generally gave slightly higher stereoselectivities
(Table 2, entries 6 and 7). More interestingly, when R was an
aliphatic group, the reaction gave only one isomer whose
absolute conguration was not identied from the 1H NMR
ꢀ
above are relatively stable and can be kept at 0 C for several
days without any change.
Table 2 Rh(II)-catalyzed reaction of diazo compounds 3a–j
With the b-ferrocenecarboxyl substituted a-diazo esters in
hand, we then proceeded to investigate their diazo decompo-
sition behavior using Rh2(OAc)4 as catalyst. First, diazo
compounds 3a–g with an aromatic ring on the b-position were
investigated. The diazo decomposition proceeded smoothly in
the presence of 0.1 mol% of Rh2(OAc)4 in anhydrous CH2Cl2 at
room temperature to afford the stereoisomeric mixture of
products 4a–g in excellent total yields (Table 2, entries 1–7). It
was found that substrates with a halogen or electron-donating
substituent on the phenyl ring, such as methyl group, gave
slightly lower stereoselectivities (Table 2, entries 1–5), while
Diazo
compounds 3
Time
(min)
Yield of
Ratio
Entry
4 (E + Z)a (%)
(E : Z)b
1
2
3
4
5
6
7
8
9
10
3a
3b
3c
3d
3e
3f
3g
3h
3i
40
40
40
40
40
60
60
40
40
40
95
94
93
94
94
96
94
92
90
92
66 : 34
68 : 32
65 : 35
65 : 35
57 : 43
73 : 27
81 : 19
—
c
—
c
3j
—
a
Yields aer column chromatographic purication with silica gel.
Ratio determined by 1H NMR (500 MHz) of the crude product.
Only one isomer was obtained.
b
c
Scheme
2 Synthesis of b-ferrocenecarboxyl a-diazocarbonyl
compounds.
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Experimental
General procedure for the preparation of b-ferrocenecarboxyl
substituted diazo compounds 3
In a dried three-necked round-bottom ask, ferrocenoyl chlo-
ride (1.1 mmol) in 2 mL of anhydrous CH2Cl2 was added
dropwise to a solution of b-hydroxy a-diazo ester 2 (1.0 mmol)
ꢀ
with pyridine (2.0 mmol) in 5 mL of anhydrous CH2Cl2 at 0 C
under N2. The resulting mixture was stirred at 0 ꢀC and the
progress of the reaction was monitored by TLC. Aer comple-
tion of the esterication reaction, saturated NaHCO3 was added
at 0 ꢀC. the organic phase was dried using Na2SO4, and solvent
was removed under reduced pressure. Next, the residue was
subjected to chromatography on silica gel to afford the
products 3a–j.
Fig. 1 X-ray structure of 4Eb.
General procedure for the Rh2(OAc)4-catalyzed reaction of 3a–j
In
a dried three-necked round-bottom ask, Rh2(OAc)4
(0.1 mol%) was dissolved into 5 mL of anhydrous CH2Cl2. A
solution of diazo substrates 3a–j in anhydrous CH2Cl2 was
added dropwise at 0 ꢀC over the course of 30 min. The reaction
mixture was stirred until TLC analysis indicated the complete
disappearance of the diazo compound. The solvent was then
removed under reduced pressure, and the crude residue was
puried by column chromatography to give the corresponding
2,3-migration products.
Scheme
3 Possible pathway for Rh2(OAc)4-catalyzed migration
reaction of b-ferrocenecarboxyl a-diazocarbonyl compound.
Acknowledgements
spectra (Table 2, entries 9 and 10). Moreover, the stereochem-
istry of the E product was further conrmed by X-ray structure of
4Eb (Fig. 1).13
Based on the experimental results above and the X-ray
structure of 4Eb as well as previous understanding of
this type of reactions,9,10 we conceived that this reaction
This project is generously supported by National Natural
Science Foundation of China (no. 21262023, 21102068 and
20902044) and the Program for Young Talents of Science and
Technology in Universities of Inner Mongolia Autonomous
Region (NJYT-12-B03).
was performed through
a facile 2,3-ferrocenecarboxyl
migration of the Rh(II)–carbene. Considering the steric
effect of the bulky ferrocene group, the 2,3-migration in this Notes and references
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