Selective palladium-catalyzed aminocarbonylation of olefins with aromatic amines and nitroarenes

Article abstract of DOI:10.1002/anie.201308455

Various olefins can be smoothly transformed in the presence of a Pd-based catalyst system and (hetero)aromatic amines or nitroarenes to synthetically interesting amides in good yields and often with high regioselectivity (see scheme). Combining this atom-efficient procedure with established functionalizations of the resulting products allows the efficient preparation of quinolines. Copyright

Full text of DOI:10.1002/anie.201308455

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DOI: 10.1002/anie.201308455
Carbonylation
Hot Paper
Selective Palladium-Catalyzed Aminocarbonylation of Olefins with
Aromatic Amines and Nitroarenes**
Xianjie Fang, Ralf Jackstell, and Matthias Beller*
Molecular-defined catalysts allow for the refinement of
readily available feedstocks to more complex functionalized
products. Prime examples for such transformations are
carbonylation processes, which make use of carbon mon-
oxide—currently the most important C1 building block.[1] In
fact, carbonylations represent industrial core reactions for
converting various bulk chemicals into a diverse set of useful
products for our daily life. More specifically, the transition-
metal-catalyzed addition of carbon monoxide to olefins or
alkynes in the presence of a suitable nucleophile, such as
water, alcohols, and amines, leads to the formation of
saturated or unsaturated carboxylic acid derivatives.[2] Nowa-
days, palladium is one of the most commonly employed
metals in these transformations. Compared with the reaction
of olefins, carbon monoxide, and alcohols (hydroesterifica-
tion) or water (hydrocarboxylation),[3] related aminocarbo-
nylations leading to amides have received much less atten-
tion. The same is also true compared to the well-studied
aminocarbonylation of alkynes,[4] intramolecular aminocar-
bonylation of alkenes,[5] and aminocarbonylation of aryl and
vinyl halides.[6] This is somewhat surprising as the amino-
carbonylation of olefins provides a 100% atom-efficient route
for producing carboxamides, which represent versatile build-
ing blocks and intermediates for the chemical, pharmaceut-
ical, and agrochemical industries.[7]
In early studies of aminocarbonylations, cobalt-carbonyl
complexes[8] or nickel cyanide[9] were used as catalysts. Iron-
carbonyl complexes[10] and ruthenium chloride[11] also showed
some catalytic activity. However, all these reactions were
carried out under very severe conditions (> 2008C;
> 150 atm). Since the 1980s, more effective catalysts, such as
ruthenium-carbonyl complexes[12] and cobalt on charcoal,[13]
have been developed. Nevertheless, the substrate scope was
limited and the reaction conditions were still harsh (1508C;
70 atm). Notably, the formation of the corresponding form-
amide by-products was hardly suppressed. Hence, so far there
exists no general and selective intermolecular aminocarbo-
nylation of different olefins under mild conditions.
Herein, we present an efficient homogeneous palladium-
based catalyst system for the aminocarbonylation of olefins
with a variety of (hetero)aromatic amines or nitro compounds
under relatively mild conditions. Notably, the corresponding
products were obtained in high yield with good regioselec-
tivity, and unwanted formamides were not observed.
In our initial investigations we examined the effect of
a series of phosphine ligands on the model reaction of 1-
octene (1a) with aniline (2a) and carbon monoxide. When
monodentate ligands were used, no conversion or just trace
amounts of the desired products were observed (Table 1,
entries 1–4). Commercially available bidentate ligands (e.g.
BINAP, Dppp, L2, and L4) showed low activity in the
formation of the desired product (Table 1, entries 5–14).
Hence, some of our own developed N-phenylpyrrole-based
bisphosphine ligands[14] with different steric properties were
tested (Table 1, entries 15–17). To our delight, L10 was
identified as the most promising ligand and the reaction
afforded the desired product 3aa with moderate conversion,
albeit with good selectivity. To improve the reaction further,
we evaluated the influence of reaction parameters such as the
molar ratio of 1a to 2a, acid co-catalyst, and solvent in the
presence of L10 as the ligand. As shown in Table 1, the yield
of 3aa was strongly affected by the molar ratio of 1a to 2a as
a consequence of some isomerization of the olefin. Con-
sequently, as the molar ratio of 1a to 2a increased to 2:1, the
yield of 3aa increased to 86% (Table 1, entry 18). Moreover,
no reaction occurred in the absence of para-toluenesulfonic
acid monohydrate (p-TsOH), thus indicating the importance
of the acid for the generation of the catalytically active
palladium hydride species (Table 1, entry 19).[15] Interestingly,
changing the THF solvent to toluene resulted in full
conversion of 2a and gave nearly quantitative yields of the
corresponding amides, as determined by GC (Table 1,
entry 20). No conversion was observed and the starting
materials were recovered in the absence of [Pd(acac)2]
(acac = acetylacetonate) or when using other catalysts such
as [Rh(CO)2(acac)], [Co2(CO)8], [Ir(cod)(acac)] (cod = 1,5-
cyclooctadiene), [Ru3(CO)12], [Fe3(CO)12], and [Ni(acac)2]
(Table 1, entry 21).
[*] X. Fang, Dr. R. Jackstell, Prof. Dr. M. Beller
Leibniz-Institut fꢀr Katalyse e. V. an der Universitꢁt Rostock
Albert-Einstein-Strasse 29a, 18059 Rostock (Germany)
E-mail: matthias.beller@catalysis.de
With the optimized reaction conditions established
(Table 1, entry 20), we examined the scope and limitations
of this aminocarbonylation process with respect to various
olefins (Table 2). Both short- and long-chain terminal olefins
1a–1e provided the corresponding amides in good to
excellent yields and with good regioselectivities (Table 2,
entries 1–4). The more challenging internal olefin 1e was
transformed to C9-amides in 53% yield. The linear amide is
still formed preferentially because of isomerization of the
olefin (66:34 n/i selectivity; Table 2, entry 5). Lower linear
Homepage: http://www.catalysis.de
[**] This research was funded by Evonik Industries, Advanced Inter-
mediates, Performance Intermediates, and the Deutsche For-
schungsgemeinschaft (Leibniz Prize to M.B.). We thank Dr. C.
Fischer, S. Buchholz, and S. Schareina for their excellent technical
and analytical support.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201308455.
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Table 2: Palladium-catalyzed aminocarbonylation of olefins (1) with
aniline (2a).[a]
Table 1: Palladium-catalyzed aminocarbonylation of 1-octene (1a) with
aniline (2a): Variation of reaction conditions.[a]
Entry
Ligand
Conversion [%][b]
Yield [%][c]
n/iso[d]
1
2
3
4
5
6
7
8
PPh3
PCy3
BuPAd2
L1
Xantphos
Naphos
BINAP
Dppp
L2
NR
trace
trace
trace
trace
trace
3
8
38
32
77:23
81:19
87:13
34
28
9
10
11
12
13
14
15
16
17
18[e]
19[f]
20[g]
21
L3
L4
L5
L6
L7
L8
L9
L10
L10
L10
L10
L10
trace
18
trace
1
trace
3
NR
46
22
5
82:18
–
7
86:14
50
89
88:12
88:12
86
NR
97
100
88:12
NR
[a] Reaction conditions: 1a (1 mmol), 2a (1 mmol), [Pd(acac)2]
(0.5 mol%), monodentate ligand (2 mol%) or bidentate ligand
(1 mol%), p-TsOH (2.5 mol%), THF (2 mL); NR=no reaction.
[b,c] Conversion and yield (based on 2a) determined by GC analysis
using isooctane as the internal standard. [d] The ratios of linear to
branched isomers were determined by GC-MS analysis. [e] 1a (2 mmol).
[f] 1a (2 mmol) and without p-TsOH. [g] 1a (2 mmol) and toluene as
solvent. BuPAd2 =n-butyldiadamantylphosphine; Xantphos=4,5-bis(di-
phenylphosphino)-9,9-dimethylxanthene; Naphos=2,2’-bis[(diphenyl-
phosphino)methyl]-1,1’-binaphthalene; BINAP=rac-(Æ)-2,2’-bis(diphe-
nylphosphino)-1,1’-binaphthyl; Dppp=1,3-bis(diphenylphosphino)pro-
pane; Ts=toluene-4-sulfanyl.
regioselectivity was observed when styrene 1 f was employed
as a substrate because of stabilization of the benzylic
palladium complex generated in situ (Table 2, entry 6). Inter-
estingly, allylbenzene and different substituted allylbenzene
derivatives were converted into the corresponding desired
products in excellent yields and high regioselectivities
(Table 2, entries 7–11). Selective aminocarbonylation reac-
tions of functionalized olefins are known to be difficult.
Gratifyingly, substrates having different functional groups
such as phthalimide, nitrile, tri-substituted olefin, and ester
[a] Reaction conditions: 1 (2 mmol), 2a (1 mmol), [Pd(acac)2]
(0.5 mol%), L10 (1 mol%), p-TsOH (2.5 mol%), toluene (2 mL).
[b] Yield of isolated linear product based on 2a; the regioselectivity was
determined by GC-MS analysis. [c] 1 (20 mmol). [d] [Pd(acac)2]
(1 mol%), [Pd]/L10/p-TsOH=1:2:5; yield determined by GC analysis
using isooctane as the internal standard. [e] [Pd(acac)2] (1 mol%), [Pd]/
L10/p-TsOH=1:2:5.
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were well-tolerated, and smoothly transformed to the corre-
sponding functionalized amides in good yields and high
selectivities for the linear product (Table 2, entries 12–15). It
is noteworthy that the corresponding formamides were not
observed in any of these cases.
Next, we varied the amine substrate and using 1-octene
(1a) as a standard coupling partner (Scheme 1). In general,
the aminocarbonylation reaction was sensitive to steric and
electronic effects of the substituent(s) on the aniline. Aniline
regioselectivities (Scheme 1, 3ae–3aj). Higher linear regio-
selectivity is observed when ortho-substituted anilines were
employed as substrates, probably because of steric effects
(Scheme 1, 3ad, 3ak, and 3al). Moreover, heteroaromatic
amines proved to be efficient coupling partners and gave the
corresponding products in good yields with high regioselec-
tivities (Scheme 1, 3am–3ao). No conversion was observed
when aliphatic amines such as butyl- or cyclohexylamine were
used. Apparently, the active Pd-H species is not formed in the
presence of the more basic aliphatic amines, as indicated by
the absence of any isomerization side reaction.
Subsequently, we became interested in the aminocarbo-
nylation of olefins by utilizing inexpensive nitroarenes. Of
course, most of the anilines are prepared from the corre-
sponding nitroarenes. Hence, this transformation would allow
the elimination of at least one process step and makes use of
less-expensive starting materials. Gratifyingly, all the individ-
ual reaction steps proceeded smoothly when molecular
hydrogen was used as the reducing agent and afforded the
desired product in acceptable to good yields (Scheme 2).
Substrates having functional groups such as nitrile and even
Scheme 2. Palladium-catalyzed aminocarbonylation of olefins (1) with
nitroarenes (4). [a] Reaction conditions: 1 (2 mmol), 4 (1 mmol),
[Pd(acac)2] (1 mol%), L10 (2 mol%), p-TsOH (5 mol%), toluene
(2 mL); yield of isolated linear product based on 4.
Scheme 1. Palladium-catalyzed aminocarbonylation of 1-octene (1a)
with aniline derivatives 2. [a] Reaction conditions: 1a (2 mmol), 2
(1 mmol), [Pd(acac)2] (0.5 mol%), L10 (1 mol%), p-TsOH (2.5 mol%),
toluene (2 mL); yield of isolated linear product based on 2; the
regioselectivity was determined by GC-MS analysis. [b] [Pd(acac)2]
(1 mol%), L10 (2 mol%), p-TsOH (5 mol%).
ketone (Scheme 2, 5d and 5 f) were well-tolerated under
these reducing conditions. In general, this latter protocol
provides a useful and benign alternative for the synthesis of
N-aryl carboxamides. To the best of our knowledge such
aminocarbonylations of olefin with nitroarenes has not been
explored before.
Although the detailed mechanism of the palladium-
catalyzed aminocarbonylation of olefins is still under inves-
tigation, we suggest the following catalytic cycle based on our
preliminary observations and the known work on carbon-
ylations of olefins and alkynes (Scheme 3).[16] Initially, the
active cationic palladium hydride species A should be formed
in situ from the reaction of [Pd(acac)2], L10, and p-TsOH.[15]
Next, p coordination of the olefin to the metal center,
followed by insertion into the hydrogen–palladium bond,
derivatives such as 2-naphthylamine, 4-chloroaniline, and 2-
fluoroaniline gave full conversion and around 80% yield of
the expected linear product in the presence of only 0.5 mol%
catalyst (Scheme 1, 3ab–3ad). Electron-rich substituted ani-
lines such as p-toluidine and p-anisidine are more sensitive
and led to lower conversion and yields of the corresponding
N-aryl C9-amides (Scheme 1, 3ae). However, when the
catalyst loading was increased to 1.0 mol%, all the reactions
of the anilines substituted with electron-rich or electron-
deficient groups proceeded smoothly and afforded the
desired products in moderate to good yields and high
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(4.75 mg, 2.5 mol%), and a stirring bar. Then, toluene (2 mL), olefin
1 (2 mmol), and aniline (2a, 1 mmol) were injected by syringe. The
vial was placed in an alloy plate, which was transferred into an
autoclave (300 mL) of the 4560 series from Parr Instruments under an
argon atmosphere. After flushing the autoclave three times with
nitrogen, the pressure of CO was increased to 40 bar CO at ambient
temperature. The reaction was performed for 20 h at 1008C. After the
reaction finished, the autoclave was cooled to room temperature and
the pressure was carefully released and isooctane (internal standard)
was added to the solution. The yield and regioselectivity were
measured by GC and GC-MS, respectively. After removing the
solvent by vacuum, the residue was directly purified by flash
chromatography on silica gel (eluent: n-heptane/ethyl acetate = 5:1)
to give the desired product 3.
Received: September 27, 2013
Published online: November 7, 2013
Scheme 3. Proposed catalytic cycle for this reaction.
Keywords: alkenes · amides · aminocarbonylation ·
.
aromatic amines · nitroarenes
should afford the alkyl-palladium intermediate C. Subsequent
insertion of CO into the palladium–alkyl bond leads to the
corresponding acyl palladium complex D. Finally, aminolysis
leads to the desired product and regenerates the palladium
hydride species A.
It should be noted that our new procedure for the
preparation of all kinds of N-aryl carboxamides also allows
for an efficient synthesis of important heterocycles. For
example, the aminocarbonylation of olefins followed by the
established Vilsmeier–Haack formylation should give rise to
a variety of bioactive quinolines. Indeed, the one-pot syn-
thesis of 6, which has been used as an intermediate for 5-
hydroxytryptamine antagonists, proceeded smoothly on
a gram scale. Starting from inexpensive 1a and aniline (2a),
6 was obtained in 66% yield after successive aminocarbony-
lation and cyclization with POCl3 and DMF [Eq. (1)].[17]
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In summary, we have developed a palladium-based
catalyst system for a general and selective aminocarbonyla-
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Notably, a wide range of olefins are efficiently transformed to
the corresponding N-(hetero)aryl amides in good yields and
often with high regioselectivity. Combining this procedure
with established functionalizations of the resulting products
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Typical procedure for the preparation of 3: Avial (4 mL) was charged
with [Pd(acac)2] (1.5 mg, 0.5 mol%), L10 (5.4 mg, 1 mol%), p-TsOH
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