Zirconocene-catalyzed sequential ethylcarboxylation of alkenes using ethylmagnesium chloride and carbon dioxide

Article abstract of DOI:10.1039/c5cc01153a

The zirconocene-catalyzed sequential ethylcarboxylation of alkenes using ethylmagnesium chloride and carbon dioxide has been developed. A range of alkenes were transformed into the corresponding carboxylic acids in high yields.

Full text of DOI:10.1039/c5cc01153a

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Zirconocene-catalyzed sequential ethylcarboxylation of
alkenes using ethylmagnesium chloride and carbon
dioxide†
Cite this: DOI: 10.1039/x0xx00000x
b*
Peng Shao,a Sheng Wang,a Chao Chen,a and Chanjuan Xia,
Received 00th January 2015,
Accepted 00th January 2015
DOI: 10.1039/x0xx00000x
www.rsc.org/
The zirconocene-catalyzed sequential ethylcarboxylation of
alkenes using ethylmagnesium chloride and carbon dioxide
has been developed. A range of alkenes were transformed to
the corresponding carboxylic acids in high yields.
Carbon dioxide is an extremely attractive carbon source that is
readily available, inexpensive, nonflammable, and inherently
renewable. Its utilization as a C1 feedstock has seen considerable
growth in recent years.1 Among them, its utilization in carboxylation
of carbon nucleophiles is a straightforward method for the synthesis
of carboxylic acids. Grignard and organolithium reagents are strong
nucleophiles which react with CO2 directly to form valuable
carboxylic acids; however, their sensitivity to moisture and poor
functional group compatibility ultimately limits their use.2 Less
reactive organoboranes,3 organozincs4 and organotin5 were found to
react with CO2 with good functional group tolerance in the presence
of a transition-metal catalyst. However, all these carboxylation
reaction required preformed organometallic reagents to react with
CO2. Thus, catalytic generation of nucleophilic organometallic
species in situ from easily available unsaturated hydrocarbons would
be highly desirable from the point of view of the atom economical
synthetic methodology. Carboxylation of styrenes6 and allenes7 with
CO2 in the presence of transition metal catalysts such as Ni, Fe, Pd
and Cu have been reported. The carboxylation of styrenes with CO2
proceeded with good selectivity to afford phenylacetic acids. The
catalytic carboxylation of allenes with CO2 provided a method for
the synthesis of allyl carboxylic acids. All these reactions proceeded
in hydrocarboxylation of unsaturated substrates. Very recently, Tsuji
Scheme 1 Zr-catalyzed ethylcarboxylation of alkenes with
ethylmagnesium chloride and carbon dioxide
Zirconocene complexes have been found extensive application as
stoichiometric reagents in organic synthesis.9 Needless to say,
catalytic process is much more expected. Cp2ZrCl2-catalyzed
addition of ethylmagnesium halides to alkenes has been reported.10
This reaction accomplishes a formation of carbon-carbon bond by
addition of an alkyl Grignard reagent to an alkene with high
regioselectivity. Furthermore, the resulting product would be
employed in further bond-forming processes. Herein we report
details of Cp2ZrCl2-catalyzed ethylcarboxylation of alkenes with
ethylmagnesium chloride and CO2.
A typical procedure is as follows (Scheme 2). To a solution of
zirconocene dichloride (0.1 mmol) in THF (2 mL) was added
EtMgCl (3 mmol) at -78 oC. The solution was stirred at room
temperature for 1 h, followed by the addition of alkene 1a (1 mmol)
o
at -78 C and stirred for 1 h. Then the reaction mixture was warmed
to room temperature and stirred for 24 h.10c Subsequently, the
reaction mixture was bubbled with CO2 for 0.5 h at room
temperature. Hydrolytic workup afforded carboxylic acid 2a in 70%
isolated yield (based on 1a) with high regioselectivity. When
EtMgCl employed in 1.5 mmol and 2.0 mmol and the product 2a
was obtained in 50% and 57% yields, respectively.
reported
a regiodivergent silacarboxylation of allenes with
silylborane and CO2 in the presence of a copper catalyst and the
regioselectivity can be highly controlled.8 As part of an ongoing
program in our laboratory to study zirconocene chemistry, we herein
describe a zirconocene-catalyzed ethylcarboxylation of alkenes with
ethylmagnesium chloride and carbon dioxide (Scheme 1). When
styrene derivatives were used and α-aryl carboxylic acids were
formed. When alkyl-substituted alkenes were used and alkanoic
acids were formed.
Scheme 2 Typical procedure of ethyl carboxylated styrene.
The scope of the reaction was investigated and the representative
results are summarized in Table 1. Pleasingly, it was found that
styrene derivatives bearing electron-donating groups worked well to
afford α-carboxylic acids. Alkyl substitution in all positions on the
aromatic ring was well tolerated (entries 2-5), giving the α-
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carboxylic acids 2b-2e in high yields. The electron-rich para-, meta-
and ortho-methoxystyrene derivatives gave the α-carboxylic acids 2f,
Notably, under this catalytic system, alkyl alkenes could also
2g and 2h in satisfied yields, respectively. 2,5-Bismethoxystyrene 1i work smoothly and the corresponding aliphatic carboxylic acids
gave α-carboxylic acid 2i in 59% yield (entry 9). However, 3,4- were produced in high efficiency. The examples are shown in Table
bismethoxystyrene 1j gave a reduced yield (entry 10), possibly due 2. The terminal alkene could bear different alkyl substituents with
to Grignard-mediated demethylation which was enhanced by functional groups. In all cases, the products are formed in high yields.
coordination to the adjacent methoxy group. In addition, when para- In contrast to Ni- and Fe-catalyzed carboxylation of alkenes,6 this
fluorostyrene, para-chlorostyrene, ortho-methylstyrene, and 2- approach enables carboxylation of compatible aliphatic alkenes.
vinylpyridine were used and carboxylic acids formed in trace. As Again, esterification of the reaction mixture by allylic bromide
example, the reaction mixture was treated with allylic bromide afforded allyl 3-ethyl-5-(4-fluorophenyl)pentanoate 3n in 62%
instead of hydrolysis to afford allyl 2-(4-isopropylphenyl)pentanoate isolated yield (entry 10).
3d in 67% isolated yield (entry 11).
aReaction conditions: Cp2ZrCl2 (0.1 mmol, 10 mol%), EtMgCl (3.0 mmol, 3
b
equiv), alkene (1, 1.0 mmol) in THF (2 mL), CO2 (1 atm). Isolated yield
c
based on alkene. The reaction mixture was treated with allylic bromide (4
mmol) at room temperature for 3 h in the presence of CuCl.
The zirconocene-catalyzed ethylmagnesation reaction of simple
monosubstituted alkenes by ethylmagnesium chloride has been
reported.10a-c In combination with known facts,
a plausible
mechanism is shown in Scheme 3. The reaction of Cp2ZrCl2 with
two molar amounts of EtMgCl and one equimolar amount of alkene
(RCH=CH2) produces zirconacyclopentane 4. The third molar
amount of EtMgCl reacts with zirconacyclopentane 4 to undergo
transmetallation followed by β-H abstraction to afford
ethylmagnesiated product 5 and regenerated Cp2Zr(ethylene). The
resulting intermediate 5 reacts with CO2 to afford magnesium acetate
66a which undergoes hydrolysis or esterification to form carboxylic
acid 2 or ester 3. To further confirm the reaction mechanism, we
aReaction conditions: Cp2ZrCl2 (0.1 mmol, 10 mol%), EtMgCl (3.0 mmol, 3
b
equiv), styrene 1 (1.0 mmol) in THF (2 mL), CO2 (1 atm). Isolated yield
c
based on alkene. The reaction mixture was treated with allylic bromide (4
mmol) at room temperature for 3 h in the presence of CuCl.
2 | Chem. Commun., 2015, 00, 1-3
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monitored the reaction by IR. For example, the IR spectra absorption
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4
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In summary, we have developed a zirconocene-catalyzed
sequential ethylcarboxylation of alkenes using ethylmagnesium
chloride and carbon dioxide. The reaction proceeds under mild
conditions in high yields with a wide range of alkenes. Styrene
and its derivatives were used to afford α-aryl carboxylic acids
and aliphatic alkenes were used to form alkanoic acids.
This work was supported by the National Natural Science
Foundation of China (21272132 and 21472106) and the
National Key Basic Research Program of China (973 program)
(2012CB933402).
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E-mail: cjxi@tsinghua.edu.cn
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† Electronic Supplementary Information (ESI) available: Experimental
procedures, full characterization including 1H NMR and 13C NMR data
and spectra for all compounds. See DOI: 10.1039/c000000x/
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