Palladium-catalyzed carboxylative coupling of benzyl chlorides with allyltributylstannane: Remarkable effect of palladium nanoparticles

Article abstract of DOI:10.1021/ol303135e

Palladium-catalyzed carboxylative coupling of benzyl chlorides with allyltributylstannane was successfully conducted to produce benzyl but-3-enoates in satisfactory to good yields. The carboxylative coupling reaction occurred smoothly under mild conditions in the presence of palladium nanoparticles in tetrahydrofuran.

Full text of DOI:10.1021/ol303135e

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Palladium-Catalyzed Carboxylative
Coupling of Benzyl Chlorides with
Allyltributylstannane: Remarkable Effect
of Palladium Nanoparticles
Xiujuan Feng,* Anle Sun, Sheng Zhang, Xiaoqiang Yu, and Ming Bao*
State Key Laboratory of Fine Chemicals, Dalian University of Technology,
Dalian 116023, China
fengxiujuan@dlut.edu.cn; mingbao@dlut.edu.cn
Received November 14, 2012
ABSTRACT
Palladium-catalyzed carboxylative coupling of benzyl chlorides with allyltributylstannane was successfully conducted to produce benzyl but-3-
enoates in satisfactory to good yields. The carboxylative coupling reaction occurred smoothly under mild conditions in the presence of palladium
nanoparticles in tetrahydrofuran.
The use of carbon dioxide (CO2) as a nontoxic, renew-
able, and low-cost carbon source to synthesize commodity
chemicals and complex organic molecules has attracted
considerable attention. Numerous methods have been
developed for CO2 fixation over the past decades.1 Among
these methods, the transition-metal-catalyzed activation
and conversion of CO2 into valuable chemicals that in-
volve new carbonÀcarbon bond formation have recently
emerged as extremely powerful tools because of their high
chemoselectivity, good functional group tolerance, and
mild reaction conditions.2 Palladium catalysts have been
successfully utilized in the carboxylation of allylstan-
nanes,3 allenes,4 and aryl halides,5 as well as in the
carboxylative coupling of allylstannanes with allyl halides,6
since the pioneering example of palladium-catalyzed cou-
pling of CO2 with 1,3-butadiene to form lactones was
reported by Inoue et al. in 1976.7,8 The key to the success
of these reactions was the use of appropriate phosphine
ligands. The carboxylative coupling of benzyl chlorides
with allylstannanes could not occur in the presence of
Pd(PPh3)4 as a catalyst.6
We have reported the facile palladium-catalyzed allyla-
tive dearomatization and carbonylative coupling reactions
of benzyl chlorides 1 with allyltributylstannane.9,10 These
(6) Franks, R. J.; Nicholas, K. M. Organometallics 2000, 19, 1458.
(7) The pioneering example of palladium-catalyzed coupling of CO2
with 1,3-butadiene was reported by the Inoue group: Sasaki, Y.; Inoue,
Y.; Hashimoto, H. J. Chem. Soc., Chem. Commun. 1976, 605.
(8) The examples of palladium-catalyzed coupling of CO2 with 1,3-
butadiene were reported by other groups: (a) Dai, Y.; Feng, X.; Wang,
B.; He, R.; Bao, M. J. Organomet. Chem. 2012, 696, 4309. (b) Buchemuller,
K.; Dahmen, N.; Dinjus, E.; Neumann, D.; Powietzka, B.; Pitter, S.;
(1) For a book, see: (a) Carbon Dioxide as a Chemical Feedstock;
Aresta, M.; Wiley-VHC: Weinheim, 2010. For a review, see: (b) Sakakura, T.;
Choi, J.-C.; Yasuda, H. Chem. Rev. 2007, 107, 2365.
(2) For reviews, see: (a) Tsuji, Y.; Fujihara, T. Chem. Commun. 2012,
48, 9956. (b) Ackermann, L. Angew. Chem., Int. Ed. 2011, 50, 3842. (c)
Correa, A.; Martın, R. Angew. Chem., Int. Ed. 2009, 48, 6201.
(3) (a) Hruszkewycz, D. P.; Wu, J.; Hazari, N.; Incarvito, C. D.
J. Am. Chem. Soc. 2011, 133, 3280. (b) Wu, J.; Hazari, N. Chem. Commun.
2011, 47, 1069 and references therein. (c) Hazari, N.; Hruszkewycz, D. P.;
Wu, J. Synlett 2011, 13, 1793.
(4) (a) Takaya, J.; Iwasawa, N. Organometallics 2009, 28, 6636. (b)
Takaya, J.; Iwasawa, N. J. Am. Chem. Soc. 2008, 130, 15254.
(5) (a) Fujihara, T.; Nogi, K.; Xu, T.; Terao, J.; Tsuji, Y. J. Am.
Chem. Soc. 2012, 134, 9106. (b) Correa, A.; Martın, R. J. Am. Chem. Soc.
2009, 131, 15794.
€
Schon, J. Green Chem. 2003, 5, 218. (c) Pitter, S.; Dinjus, E. J. Mol.
Catal. A: Chem. 1997, 125, 39. (d) Behr, A.; He, J.; Jusyak, K. D. Chem.
Ber 1986, 119, 991. (e) Behr, A.; Juszak, K. D.; Keim, W. Synthesis 1983,
7, 574. (f) Behr, A.; Juszak, K. D. J. Organomet. Chem. 1983, 255, 263.
(g) Musco, A.; Perego, C.; Tartiari, V. Inorg. Chim. Acta 1978, 28, L147.
(9) (a) Lu, S.; Xu, Z.; Bao, M.; Yamamoto, Y. Angew. Chem., Int. Ed.
2008, 47, 4366. (b) Bao, M.; Nakamura, H.; Yamamoto, Y. J. Am.
Chem. Soc. 2001, 123, 759.
(10) Dai, Y.; Feng, X.; Liu, H.; Jiang, H.; Bao, M. J. Org. Chem.
2011, 76, 10068.
r
10.1021/ol303135e
XXXX American Chemical Society

reactions proceeded smoothly via π-benzylpalladium chlo-
ride intermediates in the presence of a PPh3 ligand to pro-
duce products 2 and 3 (Scheme 1). The success in achieving
carbonylative coupling of benzyl chlorides 1 with allyltri-
butylstannane encouraged us to consider whether carbox-
ylative coupling could also occur in the presence of a novel
palladium catalyst system to offer esters.
Table 1. Reaction Condition Screeninga
entry
catalyst
additive
solvent
yield (%)b
1
Pd2(dba)3
PdCl2
TBAB
TBAB
TBAB
TBAB
none
THF
48
65
69
86
NRc
17
25
22
78
70
73
44
60
49
83
78
24
70
2
THF
Scheme 1. Coupling Reactions via π-Benzylpalladium Chloride
Intermediates
3
Pd(OAc)2
Pd(acac)2
Pd(acac)2
Pd(acac)2
Pd(acac)2
Pd(acac)2
Pd(acac)2
Pd(acac)2
Pd(acac)2
Pd(acac)2
Pd(acac)2
Pd(acac)2
Pd(acac)2
Pd(acac)2
Pd(acac)2
Pd(acac)2
THF
4
THF
5
THF
6
TBAF
TBAC
TBAI
THF
7
THF
8
THF
9d
10e
11
12
13
14
15f
16g
17h
18i
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
THF
THF
toluene
hexane
dioxane
DMF
THF
THF
As illustrated in Scheme 2, we hypothesized that the
π-benzyl π-allylpalladium intermediate B derived from
π-benzylpalladium chloride intermediate A could not un-
dergo allylative dearomatization in the absence of the PPh3
ligand. The π-benzyl and π-allyl carbon-based ligands in
intermediate B would cause the palladium center to exhibit
high basicity, which would facilitate the coordination of
CO2 to form intermediate C. The nucleophilicity of the
σ-allyl group in intermediateC would be enhanced because
ofthe π-benzyl carbon-basedligand, whichwouldfunction
like an N-heterocyclic carbene ligand.11 The nucleophi-
lic addition of the σ-allyl group to CO2 would take place
to afford π-benzylpalladium carboxylate intermediate
D,12 which would undergo reductive elimination of
the β,γ-unsaturated ester 4 (regenerating the Pd(0)
species).
THF
THF
a Reaction conditions: benzyl chloride (1a, 0.5 mmol), allytributyl-
stannane (0.6 mmol), CO2 (2 MPa), Pd catalyst (5 mol %), additive
(1.4 equiv), and solvent (5 mL) at 70 °C for 24 h. b Isolated yield. c No
reaction. d 1.2 equiv of TBAB was used. e 1.6 equiv of TBAB was used.
f The reaction was conducted under 1 MPa of CO2. g The reaction was
performed under 0.5 MPa of CO2. h The reaction was performed under
0.1 MPa of CO2. i The reaction was conducted for 12 h.
tetrabutylammonium bromide (TBAB). A relatively high
yield was obtained using Pd(II) salts as precatalysts, and
Pd(acac)2 proved to be the best precatalyst (entries 2À4 vs
entry 1). These results indicated that a Pd(0) species
generated in situ possessed higher catalytic activity than
Pd2(dba)3. The formation of the Stille coupling and ally-
lative dearomatization products was not observed. No
reaction was observed in the absence of TBAB (entry 5).
The use of a quaternary ammonium salt as an additive was
necessary to avoid palladium black generation. Thus, the
quaternary ammonium salts were screened usingPd(acac)2
as the precatalyst in THF (entries 4 and 6À8). Among the
tested quaternary ammonium salts [TBAB, tetrabutylam-
monium fluoride (TBAF), tetrabutylammonium chloride
(TBAC), and tetrabutylammonium iodide (TBAI)], the
use of TBAB as an additive produced the highest yield of
desired product 4a (entry 4, 86%). The reaction yield was
also influenced by the amount of TBAB utilized. A de-
creased yield of 4a was obtained when 1.2 or 1.6 equiv of
TBAB was employed (entry 9, 78%; entry 10, 70%). The
solvents were finally screened using Pd(acac)2 and TBAB
as the precatalyst and additive, respectively. Nonpolar
Several palladium catalystsystems were examinedtotest
this hypothesis. Benzyl chloride (1a) was used as starting
material, and the results are shown in Table 1. Precatalysts
Pd2(dba)3, PdCl2, Pd(OAc)2, and Pd(acac)2 were initially
tested in tetrahydrofuran (THF) at 70 °C in the presence of
Scheme 2. Palladium-Catalyzed Carboxylative Coupling of
Benzyl Chlorides with Allylstannane under Phosphine Ligand-
Free Conditions
(11) For a book, see: (a) N-Heterocyclic Carbenes in Synthesis; Nolan,
S. P., Ed.; Wiley-VCH: Weinheim, 2006. For a review, see: (b) Kantchev,
E. A. B.; O'Brien, C. J.; Organ, M. G. Angew. Chem., Int. Ed. 2007, 46,
2768.
(12) Wu, J.; Green, J. C.; Hazari, N.; Hruszkewycz, D. P.; Incarvito,
C. D.; Schmeier, T. J. Organometallics 2010, 29, 6369.
B
Org. Lett., Vol. XX, No. XX, XXXX

(toluene and hexane) and polar [THF, dioxane, and N,N-
dimethyl formamide (DMF)] solvents were examined
(entries 4 and 11À14). THF proved to be the best solvent
(entry 4). Further studies revealed that the yield of product
4a decreased with a decrease in CO2 pressure (entry 15:
1 MPa CO2, 83%; entry 16: 0.5 MPa CO2, 78%; entry
17: 0.1 MPa CO2, 24%). The yield of product 4a
decreased (70%) when the reaction time was shortened
(12 h, entry 18). Therefore, the subsequent palladium-
catalyzed carboxylative couplings of various benzyl
chlorides with allyltributylstannane were performed
in the presence of Pd(acac)2 as the precatalyst and using
TBAB (1.4 equiv) as the additive under 2 MPa of CO2
pressure in THF for 24 h.
Table 2. Palladium-Catalyzed Carboxylative Coupling of Ben-
zyl Chlorides with Allyltributylstannanea
Table 2 shows the results of palladium-catalyzed car-
boxylative coupling of various benzyl chlorides with allyl-
tributylstannane. Good yields similar to that of 4a were
observed when 4-fluorobenzyl chloride (1b), 4-chloroben-
zyl chloride (1c), and 4-bromobenzyl chloride (1d) were
examined under optimized reaction conditions (entries
2À4 vs entry 1, 80%À84%). Notably, the Cl and Br atoms
linked to the benzene ring were maintained in the struc-
tures of products 4c and 4d under the carboxylative
coupling reaction conditions, which suggests that further
manipulation may produce useful compounds. The reac-
tion of the 2,4-dichlorobenzyl chloride (1e) with allyltri-
butylstannane also proceeded smoothly to furnish the
desired product 4e in 80% yield (entry 5). Products 4f
and 4g were obtained in the same moderate yield (64%)
from the reactions of benzyl chlorides 1f and 1g bearing
strong electron-withdrawing groups nitro (NO2) and acet-
oxy (AcO) on the para position, respectively (entries 6 and
7). The electron density of the π-benzyl carbon-based
ligand was strongly decreased by the strong electron-with-
drawing groups NO2 and AcO that were linked to a
benzene ring. Thus, the nucleophilic reactivity of the
σ-allyl group in intermediate C was reduced (Scheme 2).
As expected, the reaction of benzyl chloride 1h that bears
an electron-donating group methyl (Me) on the para
position provided a good yield of product 4h (entry 8,
82%). Reactions of benzyl chlorides 1i to 1k that bear a
methoxy (MeO) group on the ortho, meta, or para posi-
tion provided good yields for products 4i to 4k (entries
9À11, 77%À83%). These results indicate that the reac-
tivities of the benzyl chlorides were not influenced by
substituent steric effects. Finally, chloromethyl naphtha-
lene substrates 1lÀ1n were utilized in this type of carbox-
ylative coupling reaction. Products 4lÀ4n were obtained
in 74%À86% yields (entries 12À14).
Carboxylative coupling product 4awas obtained in 70%
yield when benzyl bromide was used as a substrate (eq 1).
The β,γ-unsaturated ester products 4 obtained from the
palladium-catalyzed carboxylative coupling reaction
of benzyl chlorides with allyltributylstannane were very
stableunderthermal and acidicconditions. However, these
products could be easily transformed into the R,β-unsatu-
rated esters 5aÀ5f and 5hÀ5n under basic conditions.
Equation 2 shows that when the β,γ-unsaturated esters
4 isolated with silica gel column chromatography were
a Reaction conditions: benzyl chloride (1, 0.5 mmol), allyltributyl-
stanane (0.6 mmol), CO2 (2 MPa), Pd(acac)2 (5 mol %), TBAB (1.4 equiv),
and THF (5 mL) at 70 °C for 24 h. b Isolated yield.
passed through a short basic alumina column, the isomer-
1
ization of 4 easily occurred to provide 5. The H NMR
spectra of 5 clearly showed that the trans-isomer of 5 was
exclusively obtained in almost all cases (for details, see
Supporting Information).
Org. Lett., Vol. XX, No. XX, XXXX
C

Transmission electron microscopy (TEM) was per-
formed to investigate the reason for the high activity of
the palladium catalyst system (Pd/TBAB) in this type of
carboxylative coupling. The results are shown in Figure 1.
As expected, the TEM image shows the presence of (3.3 (1.3)-
nm-sized palladium nanoparticles in the reaction mixture.
These results reveal that the additive TBAB acted as a
stabilizer to disperse the palladium nanoparticles gener-
ated in situ by reducing Pd(acac)2 with allyltributylst-
annane.13 The palladium nanoparticles generated in situ
is known to exhibit higher catalytic activity than a relative
molecular catalyst.14 Therefore, the high activity of the
palladium catalyst system employed can be ascribed to the
formation of palladium nanoparticles.
In summary, we have developed a new type of palladium-
catalyzed carboxylative coupling reaction by utilizing
palladium nanoparticles as the catalyst. The mild reaction
conditions (low CO2 pressure and temperature), experi-
mental simplicity, and broad substrate scope are features
of the novel and general catalytic method proposed in this
paper. To the best of our knowledge, the use of metal
nanoparticles as a catalyst is the first example reported on
Figure 1. TEM image and size distribution of palladium
nanoparticles.
the catalytic CO2-fixation reaction. Further studies focusing
on the theoretical explanation of the reaction mechanism
and the extension of the reaction scope using substituted
allyltin reagents are currently underway.
Acknowledgment. We are grateful to the National Nat-
ural Science Foundation of China (Nos. 21002010 and
21073025) for their financial support. This work was also
supported by the Fundamental Research Funds for the
Central Universities [DUT12LK44, DUT13LK03, and
DUT11ZD106].
Supporting Information Available. Experimental pro-
cedures and characterization data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(13) For a review, see: (a) Astruc, D.; Lu, F.; Aranzaes, J. R. Angew.
Chem., Int. Ed. 2005, 44, 7852. For a selected reference, see: (b) Adak, L.;
Chattopadhyay, K.; Ranu, B. C. J. Org. Chem. 2009, 74, 3982.
(14) See: Reference 13a.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX