Palladium-Catalyzed Oxidative Carbonylation of Aromatic C?H Bonds with Alcohols using Molybdenum Hexacarbonyl as the Carbon Monoxide Source

Article abstract of DOI:10.1002/adsc.201600395

With molybdenum hexacarbonyl as the carbon monoxide source, a general palladium-catalyzed carbonylative transformation of the C?H bond on aromatic rings to produce esters has been developed. Good yields of the corresponding products have been obtained with wide functional group tolerance and excellent regioselectivity. A variety of aliphatic alcohols are suitable reactants here. (Figure presented.).

Full text of DOI:10.1002/adsc.201600395

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DOI: 10.1002/adsc.201600395
À
Palladium-Catalyzed Oxidative Carbonylation of Aromatic C H
Bonds with Alcohols using Molybdenum Hexacarbonyl as the
Carbon Monoxide Source
Zechao Wang,a Yahui Li,a Fengxiang Zhu,a and Xiao-Feng Wua,*
a
Leibniz-Institut fꢀr Katalyse e.V. an der Universitꢁt Rostock, Albert-Einstein-Strasse 29a, 18059 Rostock, Germany
E-mail: xiao-feng.wu@catalysis.de
Received: April 13, 2016; Revised: April 29, 2016; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201600395.
Abstract: With molybdenum hexacarbonyl as the
duce esters was reported.[5] By using Oxone as the ox-
idant under a carbon monoxide (2 bar) atmosphere,
the desired esters were formed in good to excellent
yields with primary alcohols. Compared with expen-
sive rhodium catalysts, palladium catalysts were ex-
plored in this topic as well. In 2010, Z. J. Shi and co-
workers reported a novel palladium-catalyzed ortho-
carbonylation of N,N-dimethylbenzylamines to pro-
duce the corresponding ortho-methyl benzoates.[6]
With Cu(OAc)2 as the oxidant, moderate to good
yields of the desired products were isolated. LiCl was
found to play an important role here. In 2013, B. F.
Shi and co-workers reported an interesting palladium-
catalyzed alkoxycarbonylation procedure for the syn-
carbon monoxide source, a general palladium-cata-
À
lyzed carbonylative transformation of the C H
bond on aromatic rings to produce esters has been
developed. Good yields of the corresponding prod-
ucts have been obtained with wide functional group
tolerance and excellent regioselectivity. A variety of
aliphatic alcohols are suitable reactants here.
À
Keywords: carbonylation; C H activation; molyb-
denum hexacarbonyl; palladium catalyst; 2-phenyl-
pyridines
À
thesis of aryl carboxylic esters via C H activation
under an atmospheric pressure of carbon monoxide.[7]
Carboxylic esters are important chemicals with wide With oxygen as the co-oxidant, good yields of the de-
applications in fine chemicals, natural products, and sired products can be achieved with 2-arylpyridines
polymers.[1] Traditionally, esters are mainly prepared and primary alcohols as the reactants. More recently,
from the corresponding carboxylic acids or their de- Lei[8] and Guan[9] reported their achievements on pal-
rivatives and alcohols. Alternatively, direct oxidative ladium-catalyzed carbonylative syntheses of o-amino-
À
esterifications of aldehydes, alcohols and arenes with benzoates from N-alkylanilines via C >H activation.
alcohols have been investigated as well.[2]
With a copper(II) salt, KI and oxygen as the oxida-
On the other hand, transition metal-catalyzed car- tion system, good yields of o-aminobenzoates can be
bonylation reactions have already become a powerful isolated in both cases.
tool in modern organic synthesis.[3] By incorporating
However, the above discussed procedures all re-
carbon monoxide as an inexpensive and abundant C1 quire carbon monoxide gas as the CO source and pri-
source, numerous carbonyl-containing compounds can mary or secondary alcohols as the reaction partner.
be easily prepared. Depending on the nucleophiles, Although carbon monoxide, as one of the cheapest C1
esters can be effectively produced when alcohols are sources, does hold a non-replaceable position in in-
added (called alkoxycarbonylation). However, most dustrial scale applications, its high toxicity and odour-
of the known alkoxycarbonylation procedures need less character limit its usage in laboratories. Hence,
aryl halides or analogues as the starting materials the development of new procedure based on CO sur-
which require pre-activation steps.
rogates will be interesting for the synthetic communi-
Based on the achievements in transition metal-cata- ty.[10] Among all the candidates, Mo(CO)6 as a non-
[4]
lyzed C H activation reactions, the merging of car- toxic solid is an attractive CO source.[11] Against this
À
À
bonylation and C H bond activation in ester synthesis background, we wish to report herein a general palla-
will be attractive. Indeed, some interesting transfor- dium-catalyzed oxidative carbonylation of aromatic
À
mations have been achieved recently. In 2009, a gener- C H bonds with Mo(CO)6 as the CO source. In the
al rhodium-catalyzed carbonylation of arenes to pro- presence of only 0.4 equivalent of Mo(CO)6, various
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kinds of alcohols were carbonylated in moderate to yield of the desired carbonylation product 3a was
good yields. In addition to 2-arylpyridine derivatives, formed after 18 h at 1308C (Table 1, entry 1). In our
1,2-diphenyldiazene, 1-phenyl-1H-pyrazole and 2-phe- further optimization studies, we found that the use of
nylpyrimidine are all suitable substrates here. Not BQ was essential for the formation of the carbonyla-
only primary alcohols, but also secondary and tertiary tion products 3. Presumably, BQ can facilitate the re-
alcohols are applicable as reaction partners.
ductive elimination step.[12] The yield of product 3a
Our initial investigation was started with 2-phenyl- was decreased when we changed the amounts of
pyridine (1a, 1 equiv.) and methanol (2a, 15 equiv.), NaOAc or Ag2CO3 used (Table 1, entries 2–5). Vari-
Pd(OAc)2,(10 mol%), [Mo(CO)6] (1 equiv.), BQ (ben- ous other oxidants such as Ag2O, AgNO3, Cu(OAc)2,
zoquinone, 2 equiv.), NaOAc (2 equiv.) and Ag2CO3 CuCl2, CuO, K2S2O8, and Oxone were tested in this
(3 equiv.) in chlorobenzene and, to our delight, a 45% reaction as well (Table 1, entries 6–12). However,
none of them could give improved results.
Table 1. Optimization of the reaction conditions.[a]
Then the effects of other bases and acids were in-
vestigated (Table 1, entries 13–19). NaOAc was found
to be the best base here, whereas Na2CO3, NaHCO3,
Table 2. Carbonylation of 2-phenylpyridine with different al-
cohols.[a]
[a]
Reaction conditions: 1a (0.5 mmol, 1 equiv.), 2a
(7.5 mmol, 15 equiv.), [Mo(CO)6] (0.5 mmol, 1 equiv.),
Pd(OAc)2 (0.05 mmol, 10 mol%), BQ (1 mmol, 2 equiv.),
base or acid (1 mmol, 2 equiv.) and oxidant (1.5 mmol,
3 equiv.), solvent (2 mL) for 18 h in a sealed tube.
[b]
Yields were determined by GC-MS. Isolated yield is
given in parenthesis.
[Mo(CO)6] (0.1 mmol, 0.2 equiv.).
[Mo(CO)6] (0.15 mmol, 0.3 equiv.).
[Mo(CO)6] (0.2 mmol, 0.4 equiv.).
[c]
[a]
2-Phenylpyridine 1a (0.5 mmol), alcohol 2 (7.5 mmol),
[d]
[Mo(CO)6] (0.2 mmol), Pd(OAc)2 (0.05 mmol), BQ
(1 mmol), NaOAc (1 mmol) and Ag2CO3 (1.5 mmol) in
DCE (2 mL) at 808C for 18 h, isolated yields.
[e]
[f]
[Mo(CO)6] (0.25 mmol, 0.5 equiv.).
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KOAc, K2CO3, Cs2CO3, and Li2CO3 were all found to
With the optimized conditions in hand (Table 1,
be inferior. DBU inhibited the reaction completely entry 27), a screening of different alcohols was per-
(Table 1, entry 19). No carbonylation product could formed subsequently. As shown in Table 2, various
be detected when AcOH was added (Table 1, primary, secondary and tertiary alcohols worked well
entry 20). The solvent was found to function critically under our reaction conditions and gave the corre-
in this reaction. The yield decreased to 43% when sponding esters in moderate to good yields. Neverthe-
MeOH was applied as the solvent (Table 1, entry 21) less, no desired product could be detected when
and no desired product can be observed when DMSO phenol, benzyl alcohol or amines was applied instead
(dimethyl sulfoxide) or AcOH was used (Table 1, en- of aliphatic alcohols.
tries 23 and 24). However, 81% of the desired product
Successively, various directed arenes (1b–j) were
3a can be formed when DCE (1,2-dichloroethane) screened with methanol (Table 3). Delightfully,
was applied as the reaction medium (Table 1, a series of functional groups, such as Me, OMe, CF3
entry 22). To our surprise, the yield can even be fur- and Br were compatible under our conditions, and
ther improved by using 0.4 equiv. of Mo(CO)6 gave the desired carbonylation products 4 in moder-
(Table 1, entry 27).
ate to good isolated yields (Table 3, entries 1–4). In
Table 3. Carbonylation of arenes with methanol.[a]
[a]
Reaction conditions: 1 (0.5 mmol), methanol 2a (7.5 mmol), BQ (1 mmol), [Mo(CO)6] (0.2 mmol), Pd(OAc)2
(0.05 mmol), NaOAc (1 mmol) and Ag2CO3 (1.5 mmol) in DCE (2 mL) at 808C for 18 h.
Isolated yields.
[b]
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the case of the analogues 1f and 1g, the reaction variety of primary, secondary and tertiary alcohols
worked efficiently and gave the corresponding car- can be applied as substrates here. Additionally, only
bonylation product 4f and 4g in 61% and 64% yields, 0.4 equivalent of Mo(CO)6 as a solid and safe CO
respectively. Interestingly, 1,2-diphenyldiazene, 1- source is required for this new procedure. High regio-
phenyl-1H-pyrazole and 2-phenylpyrimidine as exam- selectivity and good functional group tolerance can be
ples of substrates with easily removable directing demonstrated, the desired carbonylation products
groups were found to be suitable substrates here as were isolated in moderate to good yields.
well (Table 3, entries 7–9).[13] Nitrogen heterocycles,
such as pyrazole and pyrimidine, served as efficient
directing groups and generated the carbonylation Experimental Section
products in good yields under the optimal conditions
(Table 3, entries 7 and 8). Good yields of the desired General Procedure for Palladium-Catalyzed
products were isolated (4i–4j; 40–63%). Itꢃs important Oxidative Carbonylation
to mention that 2-ethylpyridine, aniline, acetanilide,
In a 25-mL sealed tube, a mixture of 2-substituted pyridine
N,N-dimethylbenzylamine, and N,N-dimethylbenza-
1 (0.5 mmol, 1.0 equiv.), alcohol 2 (7.5 mmol, 15 equiv.),
mide were all tested under our standard conditions,
Pd(OAc)2 (11.2 mg, 0.05 mmol, 10 mol%), Ag2CO3 (414 mg,
but no carbonylation products could be observed.
A plausible reaction pathway is proposed on the
basis of the above results and previous studies
1.5 mmol, 3.0 equiv.), Mo(CO)6 (52.8 mg, 0.2 mmol,
0.4 equiv.), BQ (108 mg, 1.0 mmol, 2 equiv.) and NaOAc
(82 mg, 1.0 mmol, 2 equiv.) in DCE (2.0 mL) was stirred at
808C under air. After 18 h, the mixture was cooled to room
temperature. The residue was diluted with H2O (10 mL) and
extracted with EtOAc (3ꢄ10 mL). The organic solvent was
then evaporated under vacuum. The crude products were
purified by using column chromatography on silica gel (pen-
tane/ethyl acetate) to give the pure products.
(Scheme 1).[14] The reaction started with C H bond
À
activation of 2-phenylpyridine 1a which generates di-
meric palladium intermediate A, that undergoes
ligand exchange to provide intermediate B. Subse-
quently, a six-membered cyclic intermediate C is gen-
erated through the coordination and insertion of CO
À
into the Pd C bond. The final product will be elimi-
nated after reductive elimination of intermediate C
promoted by BQ which could also acts as a co-oxi-
dant. The meanwhile formed Pd(0) will be re-oxidized
to Pd(II) to complete the catalytic cycle.
Acknowledgements
We thank the Chinese Scholarship Council for financial sup-
port. We appreciate the general support from Professor Mat-
thias Beller in LIKAT. We thank the analytical department of
Leibniz-Institute for Catalysis at the University of Rostock
for their excellent analytical service.
In conclusion, we have developed a mild and gener-
al procedure for palladium-catalyzed alkoxycarbony-
lation of arenes with Mo(CO)6 as the CO source. A
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6 Palladium-Catalyzed Oxidative Carbonylation of Aromatic
À
C H Bonds with Alcohols using Molybdenum
Hexacarbonyl as the Carbon Monoxide Source
Adv. Synth. Catal. 2016, 358, 1 – 6
Zechao Wang, Yahui Li, Fengxiang Zhu, Xiao-Feng Wu*
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