A Light/Ketone/Copper System for Carboxylation of Allylic C-H Bonds of Alkenes with CO2

Article abstract of DOI:10.1002/chem.201600682

A photo-induced carboxylation reaction of allylic C-H bonds of simple alkenes with CO₂ is prompted by means of a ketone and a copper complex. The unique carboxylation reaction proceeds through a sequence of an endergonic photoreaction of ketones with alkenes forming homoallyl alcohol intermediates and a thermal copper-catalyzed allyl transfer reaction from the homoallyl alcohols to CO₂ through C-C bond cleavage. An allylic C-H bond of simple alkenes is carboxylated with CO₂ in the presence of a substoichiometric amount of a ketone and a catalytic amount of a copper complex under UV irradiation (see scheme).

Full text of DOI:10.1002/chem.201600682

DOI: 10.1002/chem.201600682
Communication
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Carboxylation |Hot Paper|
A Light/Ketone/Copper System for Carboxylation of Allylic CÀH
Bonds of Alkenes with CO2
Naoki Ishida, Yusuke Masuda, Sho Uemoto, and Masahiro Murakami*[a]
Abstract: A photo-induced carboxylation reaction of allylic
CÀH bonds of simple alkenes with CO2 is prompted by
means of a ketone and a copper complex. The unique car-
boxylation reaction proceeds through a sequence of an
endergonic photoreaction of ketones with alkenes form-
ing homoallyl alcohol intermediates and
a thermal
copper-catalyzed allyl transfer reaction from the homoallyl
alcohols to CO2 through CÀC bond cleavage.
Scheme 1. Carboxylation of cyclohexene (1a).
The CÀC bond-forming carboxylation reactions of CÀH bonds
with carbon dioxide (CO2) have gained considerable attention
because of its challenging character as well as potential impor-
tance of CO2 as a chemical feedstock.[1,2] Recently, intriguing
approaches to catalytic carboxylation of CÀH bonds have been
developed on the basis of thermal reactivities of transition-
metal complexes. For example, a CÀH bond of ethylene is car-
boxylated with pressurized CO2 in the presence of a nickel cat-
alyst and a base to produce acrylic acid.[2j,l] A CÀH bond of
benzene is carboxylated with an atmospheric pressure of CO2
with the aid of a rhodium catalyst and a stoichiometric
amount of an alkylaluminum reagent.[2m] These methods have
demonstrated the potential of CÀC bond-forming carboxyla-
tion reactions of C(sp2)ÀH bonds with CO2. On the other hand,
it still remains difficult to carboxylate C(sp3)ÀH bonds, includ-
ing relatively reactive allylic and benzylic ones. Here we report
an allylic CÀH bond of simple alkenes is carboxylated with CO2
in the presence of a substoichiometric amount of a ketone
and a catalytic amount of a copper complex under UV irradia-
tion.[3]
2.0 mL, 20 mmol), ketone 2a (0.05 mmol), copper complex 3
(0.01 mmol),[5] and t-BuOK (1.0 mmol) was prepared in a Pyrexꢀ
flask equipped with a screw cap under a nitrogen atmosphere.
The atmosphere was replaced with CO2 using a balloon, and
then the flask was closed with the screw cap. The reaction
vessel was heated at 110 8C and was irradiated with an LED
lamp (365 nm). After 12 h, the reaction mixture was subjected
to the conventional acid–base extraction to afford 0.45 mmol
of b,g-unsaturated carboxylic acid 4a.[6,7] This result indicates
that the amount of the carboxylated product was more than
the amount of both the ketone 2a (turnover number, TON=9)
and the copper complex 3 (TON=45). Although the yield
based on cyclohexene was approximately 2.3%, other cyclo-
hexene mostly remained intact (97% according to GC analysis).
Only small amounts of byproducts, including 3,3’-bicyclohexen-
yl, were detected. Several control experiments were carried
out for comparison.[8] The use of 1.0 mmol of cyclohexene
under the otherwise same reaction conditions resulted in no
carboxylation, indicating high concentration of cyclohexene is
required. No carboxylation took place in the absence of either
the ketone 2a, copper complex 3 or UV light. The use of other
ketones, like simple xanthone (2b), thioxanthone, benzophe-
none, and acetophenone, gave 4a albeit in lower yield.
Copper–phosphine complexes, like [(binap)CuCl] and [(xant-
phos)CuCl], failed to afford the carboxylated product.
Recently, we have developed synthetic transformations ex-
ploiting light as the energy source.[4] The fundamental mecha-
nism consists of two stages; 1) an endergonic photoreaction
forming highly energetic intermediates, and 2) a subsequent
transition-metal-catalyzed reaction of the resulting energetic
intermediates. In the course of our studies, we discovered that
cyclohexene (1a) underwent a carboxylation reaction at the al-
lylic position with the aid of catalytic amounts of ketone 2a
and copper complex 3 under UV irradiation (Scheme 1). Initial-
ly, a solution containing benzene (8.0 mL), cyclohexene (1a;
A proposed mechanism for the carboxylation reaction is de-
picted in Scheme 2. Initially, the ketone 2 is excited by photoir-
radiation. The carbonyl oxygen of excited ketone 2 abstracts
hydrogen of the allylic CÀH bond of 1a, which has a smaller
bond dissociation energy than other CÀH bonds. The geminate
radical pair 5 is generated, and a radical–radical coupling reac-
tion follows to give tertiary homoallyl alcohol 6.[9] It should be
noted that the formation of 6 from 1a and 2 is endergonic.
According to DFT calculations at B3LYP/6-31G(d) level, a reac-
[a] Dr. N. Ishida, Y. Masuda, S. Uemoto, Prof. Dr. M. Murakami
Department of Synthetic Chemistry and Biological Chemistry
Kyoto University, Katsura, Kyoto 615-8510 (Japan)
E-mail: murakami@sbchem.kyoto-u.ac.jp
Supporting information for this article can be found under
http://dx.doi.org/10.1002/chem.201600682.
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Communication
been previously reported by Oshima and cowor-
kers.[11b] Carboxylic acid 4a was obtained in 52%
yield, and xanthone (2b) was regenerated in 59%
yield. These results are consistent with the proposed
mechanism in which both the xanthone 2a and the
copper complex 3 operate for carboxylation of cyclo-
hexene (1a) in a catalytic manner.
It is worth noting that the photoreaction of the
ketone and the copper-catalyzed carboxylation reac-
tion are successfully operative in the single flask, be-
cause transition-metal complexes usually absorb light
more efficiently than ketones to cause decomposition
Scheme 2. Proposed mechanism.
of the complex and/or suppression of photoreactions
of ketones. One of the key factors for success of the
tion of 1a and simple xanthone (2b) giving 6a is DH= +17.4,
present carboxylation reaction is that the copper complex 3
barely absorbs the light of wavelength employed (365 nm).[8]
Next examined was the carboxylation reaction of other
simple alkenes (Table 1).[16] Cycloalkenes like cyclopentene (1b)
and cycloheptene (1c) were carboxylated to give the corre-
sponding carboxylic acids 4b and 4c (entries 1 and 2). 1,1-Di-
substituted alkene 1d underwent site-selective carboxylation
to furnish 4d (entry 3). In case of monosubstituted alkene 1e,
decomposition of the ketone catalyst is faster than the case of
other alkenes, decreasing the TON of the ketone to 1.3
(entry 4). On the other hand, the copper complex 3 kept its ac-
tivity during the present reaction conditions (TON=33). The
isomeric mixture of alkenylacetic acids was produced in a ratio
of 91:9. The major isomer has the carboxyl group at the inter-
nal position. The carboxylation reaction of tetrasubstituted
alkene 1g selectively took place in a carbonyl-ene-type
manner, affording carboxylic acid 4g (entry 6). We assume the
site-selectivity observed with 1d–1g is attributable to the
copper-catalyzed carboxylation step on the basis of the follow-
ing facts; the photoreaction of 1g with xanthone (2b) afforded
the isomeric mixture of homoallyl alcohols 6g and 6g’, and
the mixture was transformed into the product 4g in a conver-
gent manner (Scheme 4). A probable scenario for the site-se-
lectivity of the carboxylation step is shown in Scheme 4c. The
allylcopper intermediate 9g is in equilibrium with 9g’ through
1,3-copper migration. The sterically less congested 9g’ is ther-
modynamically more stable than the more congested 9g. The
more stable isomer 9g’ selectively undergoes an addition reac-
tion onto CO2 via the six-membered transition state with mi-
gration of the double bond. As a result, the carboxyl group is
introduced at the sterically more crowded position. Asymmetri-
cally substituted alkenes 1h and 1i, which have two distinctly
different CÀH bonds at the allylic position, afforded mixtures
of isomers, indicating unselective hydrogen abstraction by the
excited xanthone 2a (entries 7 and 8). b-Pinene, a naturally oc-
curring monoterpene, potentially causes an issue of diastereo-
selectivity as well as site-selectivity. Nonetheless, the carboxyla-
tion reaction took place selectively at the methylene carbon
from the sterically less hindered face to furnish the b-pinene
carboxylic acid 4j, although the TON of xanthone (2b) was de-
creased to 1.3 (entry 9).
DG= +30.3 kcalmolÀ1 [8]
Thus, this photochemical process
.
charges energy into cyclohexene (1a) to furnish the more en-
ergetic tertiary homoallyl alcohol intermediate 6. Then, alcohol
6 is deprotonated by copper tert-butoxide 7 arising from 3
and tBuOK. The resulting copper alkoxide 8 undergoes a CÀC
bond-cleaving reaction[10] through b-carbon elimination[11] to
furnish ketone 2 and allylcopper species 9. Ketone 2 goes back
to the next photoreaction cycle, and the allylcopper species 9
enters the carboxylation cycle.[12] The nucleophilic addition re-
action of 9 to CO2 produces the copper carboxylate 10. Subse-
quent ligand exchange with tBuOK affords the carboxylate salt
11, and simultaneously, regenerates the copper tert-butoxide
catalyst 7.[13]
Following control experiments were carried out to support
the proposed reaction pathway (Scheme 3). When a mixture of
cyclohexene (1a; 2.0 mL) and xanthone (2b; 1.0 mmol) in ben-
Scheme 3. Control experiments.
zene (8.0 mL) was irradiated with UV light, the homoallyl alco-
hol 6a was produced as the major product (70% isolated yield
based on 2b). Although the excited carbonyl group can under-
go a [2+2] cycloaddition reaction with alkenes (Paterno–Büchi
reaction),[14] such a reaction was a minor pathway under the
present reaction conditions.[15] Next, the resulting alcohol 6a
was treated with a catalytic amount of copper catalyst 3
(5 mol%) and 2 equiv of tBuOK under an atmospheric pressure
of CO2 in the absence of light. The allyl group of homoallyl al-
cohol 6a was transferred onto CO2 in a manner analogous to
the reaction of homoallyl alcohols with aldehydes, which has
In conclusion, we have described that an allylic CÀH bond of
simple alkenes is carboxylated with CO2 in the presence of
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Table 1. Carboxylation of various alkenes.[a]
Entry
1
Alkene 1
Product 4[b]
TON[c]
11
53
3.4
17
2
3
3
15
1.3
33
4[d]
4.2
21
5
11
53
6
7
6
30
Scheme 4. Carboxylation of 1g in sequence.
2.2
11
ness: 1.2 mm). The Schlenk tube was taken out of the glovebox
and filled with CO2 by vacuum-refill cycles at À788C. After heating
to 110 8C, the Schlenk tube was irradiated with an LED lamp
(365 nm) for 12 h. (CAUTION: The internal pressure estimated on the
basis of the ideal gas law is approximately 2 atm under the present
reaction conditions. A pressure-proof vessel must be used for safety.)
The reaction mixture was quenched with 2N HCl aq., and the
aqueous layer was extracted with Et2O (3 times). The combined or-
ganic layer was washed with water (3 times) and extracted with 2N
NaOH aq. (3 times). The combined aqueous layer was acidified
with 2N HCl aq., then extracted with Et2O (3 times), washed with
sat. NaCl aq. and dried over Na2SO4. The solvent was removed
under reduced pressure to afford the carboxylic acid 4.
8
1.3
33
9[d]
[a] Reaction conditions: 1 (2.0 mL), 2a (0.05 mmol), 3 (0.01 mmol), tBuOK
(1.0 mmol), CO2, benzene (8.0 mL), 110 8C in a sealed tube, 12 h. [b] Isolat-
ed yields. [c] Turnover numbers (TON) of ketone 2 (upper) and copper
complex 3 (lower). [d] 1 (2.0 mL), 2b (0.10 mmol), 3 (0.004 mmol) were
used.
a substoichiometric amount of a ketone and a catalytic
amount of a copper complex under UV irradiation. Mechanisti-
cally, a sequence of 1) a photochemical endergonic reaction of
the ketone and alkenes forming homoallyl alcohol intermedi-
ates and 2) a copper-catalyzed allyl transfer reaction from ho-
moallyl alcohols to CO2 through a CÀC bond cleavage is opera-
tive in the carboxylation reaction.
Acknowledgements
This work was supported in part by Grants-in-Aid for Scientific
Research on Innovative Areas “Molecular Activation Directed
toward Straightforward Synthesis” (22105005), Grants-in-Aid
for Scientific Research (S) (15H05756) from MEXT, the ACT-C
Program of the JST, and Yazaki Memorial Foundation for Sci-
ence and Technology. Y.M. acknowledged JSPS fellowship for
young scientists.
Experimental Section
Keywords: carbon dioxide · CÀC activation · CÀH activation ·
copper · synthetic method
A general procedure for carboxylation of alkenes
Inside a glovebox, [(IPr)CuCl] (3; 4.9 mg, 0.01 mmol), 3,6-diphenyl-
xanthone (2a; 17.4 mg, 0.05 mmol), KOtBu (112 mg, 1.0 mmol),
alkene 1 (2.0 mL), and benzene (8.0 mL) were placed in a J-Young
type Schlenk tube (volume: 18 mL, diameter: 20 mm, glass thick-
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the carbonyl group of 2b with cyclo-
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Received: February 14, 2016
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Published online on March 21, 2016
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