Domino-Hydroformylation/Aldol Condensation Catalysis: Highly Selective Synthesis of α,β-Unsaturated Aldehydes from Olefins

Article abstract of DOI:10.1002/chem.201403302

A general and highly chemo-, regio-, and stereoselective synthesis of α,β-unsaturated aldehydes by a domino hydroformylation/aldol condensation reaction has been developed. A variety of olefins and aromatic aldehydes were efficiently converted into various substituted α,β-unsaturated aldehydes in good to excellent yields in the presence of a rhodium phosphine/acid-base catalyst system. In view of the easy availability of the substrates, the high atom-efficiency, the excellent selectivity, and the mild conditions, this method is expected to complement current methodologies for the preparation of α,β-unsaturated aldehydes.

Full text of DOI:10.1002/chem.201403302

DOI: 10.1002/chem.201403302
Full Paper
&
Organic Synthesis
Domino-Hydroformylation/Aldol Condensation Catalysis: Highly
Selective Synthesis of a,b-Unsaturated Aldehydes from Olefins
Xianjie Fang,[a] Ralf Jackstell,[a] Robert Franke,[b, c] and Matthias Beller*[a]
Abstract: A general and highly chemo-, regio-, and stereo-
selective synthesis of a,b-unsaturated aldehydes by
a domino hydroformylation/aldol condensation reaction has
been developed. A variety of olefins and aromatic aldehydes
were efficiently converted into various substituted a,b-unsa-
turated aldehydes in good to excellent yields in the pres-
ence of a rhodium phosphine/acid–base catalyst system. In
view of the easy availability of the substrates, the high
atom-efficiency, the excellent selectivity, and the mild condi-
tions, this method is expected to complement current meth-
odologies for the preparation of a,b-unsaturated aldehydes.
Introduction
a,b-Unsaturated aldehydes represent an important class of fine
chemicals possessing a broad spectrum of applications in food,
cosmetic, agrochemical, and pharmaceutical industries.[1] Addi-
tionally, they also serve as valuable intermediates in numerous
organic syntheses.[2] Therefore, many practical methods, includ-
ing oxidations of allylic alcohols,[3] Peterson olefinations,[4] for-
mylations,[5] Heck reactions,[6] Aldol condensations,[7] Saegusa
oxidations,[8] and hydroformylation of alkynes[9] have been de-
veloped in this regard. Nevertheless, many of these protocols
suffer from drawbacks that include relatively harsh reaction
conditions, the use of prefunctionalized substrates, high cata-
lyst loading, generation of halogenated wastes, and limited se-
lectivity (chemo-, regio-, and stereoselectivity). In this respect,
the development of more efficient and atom-economic meth-
odologies is of high importance. Obviously, the selective
domino-hydroformylation/aldol condensation reaction pro-
vides an ideal and straightforward pathway to overcome the
above-mentioned difficulties/limitations (Scheme 1).
Scheme 1. Efficient synthesis of a,b-unsaturated aldehydes by a domino-
hydroformylation/aldol condensation reaction.
tions of this transformation are used for the production of bulk
chemicals.[12] Due to the versatile chemistry of the aldehyde
group,[13] the resulting products are further converted by re-
duction, oxidation, or other reactions to give alcohols, amines,
carboxylic acid derivatives, aldol condensation products, and
many others. Following a general trend in organic chemistry,[14]
hydroformylation can also be integrated in tandem or domino
reaction sequences. Thus, many reactions of the metal–acyl in-
termediates or the final aldehydes can be achieved directly
under hydroformylation conditions as collected in Scheme 2.[15]
However, the additional reagents, products or variations of re-
action conditions optimized for the hydroformylation step,
may suppress or hinder the initial hydroformylation step which
is not trivial in all cases.
Hydroformylation of olefins to give aldehydes as predomi-
nant products, discovered by Otto Roelen in 1938, is an in-
triguing and extensively studied reaction.[10,11] Owing to its in-
herent industrial importance, the hydroformylation of aliphatic
olefins has been widely explored. Nowadays, major applica-
[a] X. Fang, Dr. R. Jackstell, Prof. Dr. M. Beller
Leibniz-Institut fꢀr Katalyse e.V. an der Universitꢁt Rostock
Albert-Einstein-Str. 29a, 18059 Rostock (Germany)
E-mail: Matthias.Beller@catalysis.de
[b] Prof. Dr. R. Franke
Evonik Industries AG
Paul-Baumann-Str. 1, 45772 Marl (Germany)
[c] Prof. Dr. R. Franke
Lehrstuhl fꢀr Theoretische Chemie
Ruhr-Universitꢁt Bochum
44780 Bochum (Germany)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201403302.
Scheme 2. Selected examples of domino and tandem reactions including
hydroformylation reactions.
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In general, aldol products are only observed as unwanted
side products in olefin conversions under hydroformylation
conditions. However, for a successful domino hydroformylation
aldol condensation sequence efficient and aldol addition of
the enolized aldehyde to another aldehyde product has to
occur. Even more challenging is the selective cross-aldol reac-
tion of two different aldehydes present under hydroformyla-
tion conditions due to the usual problems of chemo- and re-
gioselectivity. Compared to the well-studied domino hydrofor-
mylation/reductive amination reactions (the so-called hydro-
aminomethylation)[16] and hydroformylation/hydrogenation re-
actions (the so-called hydroxymethylation),[17] the related
domino-hydroformylation/aldol condensation reaction of ole-
fins to give a,b-unsaturated aldehydes has received only
scarce attention. In early studies, it has been found that hydro-
formylation/aldol condensation reaction sequences usually
suffer from low chemoselectivity and/or low yield of the de-
sired unsaturated aldehyde, primarily because the formation of
the corresponding saturated aldehydes and alcohols can be
hardly suppressed under the harsh conditions.[18] However, Eil-
bracht and co-workers reported
Results and Discussion
To develop the catalytic system for a general synthesis of a,b-
unsaturated aldehydes from olefins, the reaction of 1-octene
1a to give 2-heptylundec-2-enal 3a was chosen as a model
system. Initial attempts were carried out in the presence of
[Rh(acac)(CO)2] (acac=acetylacetone) and Naphos (L6). This
ligand was previously applied by us and allows for highly re-
gioselective rhodium-catalyzed hydroformylation reactions.[22]
In general, catalytic experiments were performed at 658C in
the presence of 0.1 mol% of [Rh(acac)(CO)2] and 0.2 mol% of
L6 under 10 bar of syngas. To control the aldol condensation
step appropriately, several bases and acids were tested under
the established hydroformylation conditions. When simple
NaOH was used as catalyst for the aldol condensation step,
nonanal 2a was obtained smoothly from 1-octene 1a but to
our surprise no condensation product 3a was formed (Table 1,
entry 1). Unfortunately unlike previous reports,[19–21] the conver-
sion was slightly decreased and only a trace amount of con-
densation product 3a was formed using the standard catalyst
intramolecular hydroformylation/
Table 1. Domino hydroformylation/homoaldol condensation of 1-octene 1a: Cocatalyst effect.[a]
aldol reactions to synthesize car-
bocyclic ring products for which
unsaturated silyl enol ethers
were utilized as substrates to
avoid the problems of chemo-
and regioselectivity.[19] Further-
more, the same group described
a strategy of combining metal
catalysis and organocatalysis to
realize intermolecular hydrofor-
mylation/aldol reactions. In this
case cyclic olefins or styrene
were used as substrates to avoid
regioselectivity problems of the
hydroformylation step. More-
over, only acetone and cyclopen-
tanone were used as C-nucleo-
philes in this case.[20] Interesting-
ly, recently the first enantioselec-
tive intermolecular sequential
hydroformylation/cross-aldol
Entry
Cocatalyst
Conversion
[%][b]
Yield [%] 2a
(n/iso)[c]
Yield [%] 3a
(E/Z)[d]
1
2
3
4
5
6
7
8
NaOH
l-proline
pyrrolidine
benzoic acid
pyrrolidine and benzoic acid
piperidine and benzoic acid
morpholine and benzoic acid
thiomorpholine and benzoic acid
diethylamine and benzoic acid
n-butylamine and benzoic acid
pyridine and benzoic acid
triethylamine and benzoic acid
pyrrolidine and AcOH
99
87
97
98
100
98
98
98
98
89
99
98
100
100
100
96 (76:24)
76 (93:7)
79 (98:2)
95 (95:5)
3 (66:34)
27 (63:37)
46 (82:18)
52 (82:18)
27 (93:7)
26 (65:35)
95 (90:10)
95 (92:8)
14 (88:12)
91 (76:24)
91 (73:27)
0
3 (89:11)
4 (99:1)
0
90 (96:4)
62 (96:4)
30 (92:8)
25 (91:9)
68 (94:6)
40 (95:5)
0
9
10
11
12
13
14
15
0
81 (97:3)
0
0
pyrrolidine and methylsulfonic acid (MSA)
pyrrolidine and p-toluenesulfonic acid (PTSA)
[a] Reaction conditions: 1a (1.5 mmol), [Rh(acac)(CO)2] (0.1 mol%), Naphos (0.2 mol%), cocatalyst (10 mol%),
CO/H2 (10 bar), EtOAc (2 mL), 658C, 24 h. [b] Conversion determined by GC analysis using isooctane as the in-
ternal standard. [c] Yield and the ratios of linear to branch isomers determined by GC analysis using isooctane
as the internal standard. [d] Yield determined by GC analysis using isooctane as the internal standard; the
ratios of E to Z isomers were determined by GCMS analysis.
process has been reported by
Breit et al.[21] but this process re-
quires a large excess of olefin or
aldehydes and its substrate
scope is still limited. In summary,
until today there exists no gen-
eral methodology for intermolecular hydroformylation/aldol
condensation reactions to give a,b-unsaturated aldehydes.
Herein, we present the combination of a specific rhodium(I)
phosphine complex and pyrrolidinium benzoate as an efficient
catalyst system for practical intermolecular domino-hydrofor-
mylation/aldol condensation reactions. Both industrially and
synthetically important olefins are selectively transformed into
the desired products under mild conditions.
for aldol reactions, l-proline (entry 2). Changing the co-catalyst
to organic base, the addition of pyrrolidine resulted in good
yield of nonanal 2a, but still a very low yield of the desired
enal product 3a was observed (entry 3). Moreover, we investi-
gated the influence of several acids in this reaction step. As an
example, benzoic acid showed no activity for the aldol con-
densation step (entry 4). Since the formation of more reactive
enamines is catalyzed by acids,[23] next we applied a combina-
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tion of pyrrolidine and benzoic acid as a co-catalyst system.
Gratifyingly, the desired enal product 3a was obtained in high
yield and with high stereoselectivity (90% yield, E/Z=96/4;
entry 5). As shown in Table 1, the desired condensation prod-
uct 3a was also obtained in the presence of benzoic acid and
other amines (entries 6–10). However, the combination of ben-
zoic acid with pyridine and triethylamine did not result in any
condensation product (entries 11 and 12). Next, the combina-
tion of pyrrolidine with different acids was investigated. While
methanesulfonic acid and p-toluenesulfonic acid monohydrate
provided no condensation product, the use of a weaker acid
(i.e. acetic acid) resulted in condensation product 3a in 81%
yield along with 14% of nonanal (entries 13–15).
Table 2. Domino-hydroformylation/homoaldol condensation of 1-octene
1a: Variation of reaction conditions.[a]
With a suitable catalyst system for the aldol condensation
step in hand, we elaborated the influence of different ligands
on this domino reaction under the established aldol condensa-
tion conditions. Low conversion and no corresponding alde-
hydes were observed in the absence of phosphine ligands
(Table 2, entry 1). When standard monodentate phosphines or
phosphites were used, low yields of the desired enal products
were obtained, primarily because of the low n-regioselectivity
of the hydroformylation step (entries 2 and 3). DPEphos L3
showed low activity for the hydroformylation reaction
(entry 4). Moderate yields of enal products were obtained
using highly active bidentate phosphite ligands for the hydro-
formylation reaction (i.e. L4 and L5), which might be explained
due to their instability under acidic conditions (entries 5 and
6). Furthermore, the yield of 3a slightly decreased when
a Naphos derivative (Iphos) L7 was employed (entry 7). Finally,
we evaluated the influence of critical reaction parameters,
such as the concentration of the organocatalyst, syngas pres-
sure, and reaction temperature, in the presence of L6 as
ligand. As shown in Table 2, using 5 mol% of acid/base catalyst
resulted in the same yield of 3a; however, at lower loading of
the co-catalysts the yield of 3a decreased significantly (en-
tries 8 and 9). Lowering the syngas pressure resulted in nearly
full conversion of 1a, but just a moderate yield of the desired
product 3a was obtained (entry 10). Low conversion was ob-
served when lowering the reaction temperature (entry 11).
The progress of the hydroformylation/homoaldol condensa-
tion sequence of 1-octene 1a was examined under the opti-
mized reaction conditions (Figure 1). Notably throughout the
course of the reaction, the initial hydroformylation product 2a
is present as a minor component (<5%). A simultaneous de-
crease of 1a and increase of the condensation product, respec-
tively, over the period of 10 h is observed. Apparently, the hy-
droformylation of 1-octene is the rate-determining step in this
hydroformylation/homoaldol condensation reaction.
Entry Ligand Conversion [%][b] Yield [%] 2a (n/iso)[c] Yield [%] 3a (E/Z)[d]
1
2
3
4
5
6
7
–
12
100
99
36
86
99
99
98
100
98
0
0
L1
L2
L3
L4
L5
L7
L6
L6
25 (1:99)
31 (1:99)
10 (62:38)
17 (50:50)
4 (1:99)
0
3 (66:34)
14 (88:12)
0
15 (>99:1)
20 (>99:1)
17 (>99:1)
39 (94:6)
58 (96:4)
80 (96:4)
90 (96:4)
70 (95:5)
68 (96:4)
7 (>99:1)
8[e]
9[f]
10[g] L6
11[h] L6
16
8 (50:50)
[a] Reaction conditions: 1a (1.5 mmol), [Rh(acac)(CO)2] (0.1 mol%), mono-
dentate ligand (1.0 mol%), bidentate ligand (0.2 mol%), pyrrolidine
(10 mol%), benzoic acid (10 mol%), CO/H2 (10 bar), EtOAc (2 mL), 658C,
24 h. [b] Conversion determined by GC analysis using isooctane as the in-
ternal standard. [c] Yield and the ratios of linear to branch isomers deter-
mined by GC analysis using isooctane as the internal standard. [d] Yield de-
termined by GC analysis using isooctane as the internal standard; the
ratios of E to Z isomers were determined by GCMS analysis. [e] Pyrrolidine
(5 mol%), benzoic acid (5 mol%). [f] Pyrrolidine (2.5 mol%), benzoic acid
(2.5 mol%). [g] CO/H2 (5 bar). [h] Reaction temperature: 508C.
and with high stereoselectivities (Table 3, entries 8 and 9). Grat-
ifyingly, substrates containing different functional groups, such
as amine, olefin, halide, and ether were well tolerated and
smoothly transformed to the corresponding functionalized
a,b-unsaturated aldehydes in good yields with high stereo-
selectivities (entries 9–12).
With the optimized reaction conditions established (Table 2,
entry 8), we examined the generality of this process with re-
spect to various olefins (Table 3). Both short- and long-chained
terminal olefins 1a--g provided the corresponding a,b-unsatu-
rated aldehydes in good to excellent yields and with high ste-
reoselectivity (E/Z ratios: >95/5; entries 1–7). When the orga-
nocatalyst loading was increased to 20 mol%, also sterically
crowded olefins 1h and 1i were smoothly transformed into
the corresponding a,b-unsaturated aldehydes in good yields
Next, we turned our attention to the challenging hydrofor-
mylation/cross-aldol reaction of 1-octene 1a with benzalde-
hyde 4a. In general, the difficult task in this reaction is to
avoid the formation of the homoaldol product 3a. Indeed, the
developed reaction protocol provided almost equimolar
amounts of 5aa and 3a (Table 4, entry 1), which prompted us
to further control the chemoselectivity. To our delight, chang-
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Table 3. Domino-hydroformylation/homoaldol reaction of various olefins 1.[a]
Entry
1
3
Yield
[%]
(E/Z)[b]
89
(96:4)
1
96
(>99:1)
2[c]
Figure 1. Compound distribution of the domino-hydroformylation/homoal-
dol condensation sequence. Reaction conditions: 1-octene (7.5 mmol), [Rh-
(acac)(CO)2] (0.1 mol%), L6 (0.2 mol%), pyrrolidine (5 mol%), and benzoic
~
69
(96:5)
3
&
*
acid (5 mol%), CO/H2 (10 bar), EtOAc (10 mL), 658C, 10 h. : 1a; : 2a;
3a.
:
81
(97:3)
4
5
ing the solvent from EtOAc to N-methyl-2-pyrrolidone (NMP)
led to only traces of homoaldol product 3a and a high yield of
the desired crossaldol product 5aa was observed (entry 2).
Notably, directly using nonanal 2a with benzaldehyde 4a as
a control experiment in the presence of the acid/base co-cata-
lyst revealed the formation of two equivalents of the homoal-
dol products compared to the cross-aldol product with moder-
ate conversion (based on nonanal) [Eq. (1)]. In essence, such
a general problem of chemoselectivity can easily be resolved
by our domino-hydroformylation/cross-aldol protocol, presum-
ably attributed to the low concentration of nonanal 2a com-
pared to benzaldehyde 4a during the course of the reaction.
Indeed, the kinetic examination of the domino-hydroformyla-
tion/cross-aldol condensation of 1-octene 1a with benzalde-
hyde 4a under the optimal reaction conditions revealed in the
first 7 h of the reaction a very small concentration of nonanal
(<1%). As shown in Figure 2, parallel to the decrease of the
concentration of the starting materials (1-octene 1a and ben-
zaldehyde 4a) an increase of the desired condensation prod-
85
(>99:1)
91
(97:3)
6
7
89
(97:3)
86
(99:1)
8[d]
75
(97:3)
9[d]
78
(>99:1)
10[d]
69
(97:3)
11[d]
92
(95:5)
12
Figure 2. Compound distribution of domino-hydroformylation/cross-aldol
condensation. Reaction conditions: 1-octene (7.5 mmol), benzaldehyde
(7.5 mmol), [Rh(acac)(CO)2] (0.1 mol%), L6 (0.2 mol%), pyrrolidine (5 mol%),
[a] Reaction conditions: 1 (15 mmol), [Rh(acac)(CO)2] (0.1 mol%), L6 (0.2 mol%),
pyrrolidine (5 mol%), and benzoic acid (5 mol%), CO/H2 (10 bar), EtOAc (20 mL),
658C, 16 h. [b] Isolated yield; the ratios of E to Z isomers were determined by
GCMS analysis. [c] [Rh(acac)(CO)2] (0.01 mol%), L6 (0.02 mol%), yield determined
by GC analysis. [d] Pyrrolidine (20 mol%) and benzoic acid (20 mol%).
&
and benzoic acid (5 mol%), CO/H2 (10 bar), NMP (10 mL), 658C, 10 h. : 4a;
~
!
*
: 1a; : 2a; : 5aa.
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cross-aldol condensation sequence with respect to aro-
matic aldehydes and olefins (Table 5). Generally, vari-
ous benzaldehydes with electron-neutral, -deficient,
and -rich substituents underwent efficient transforma-
tion to afford the corresponding a,b-unsaturated alde-
hydes in good to excellent yields with high E stereose-
lectivities (5aa–ai; Table 5). Meanwhile, aldehydes con-
taining different functional groups such as halide, ni-
trile, and nitro, were well tolerated, too (5ab–ad and
5ag–ah). Moreover, heterocyclic aldehydes proved
also to be efficient coupling partners to generate the
corresponding products in good yields (5aj–al). From
a synthetic point of view, the synthesis of functional-
ized a,b-unsaturated aldehydes from functionalized
olefins and aromatic aldehydes is important, which is
reflected in products 5ka and 5ia, which are obtained
in good yield when using our protocol. A point to
note is that all the yields of the corresponding homo-
Table 4. Domino hydroformylation/cross-aldol reaction of 1a with 4a: Solvent ef-
fect.[a]
Entry
Solvent Conversion [%][b] Yield [%] 5aa (E/Z)[c] Yield [%] 3a (E/Z)[c]
1
2
EtOAc
NMP
98
94
42 (95:5)
90 (96:4)
36 (97:3)
trace
[a] Reaction conditions: 1a (1.5 mmol), 4a (1.5 mmol), [Rh(acac)(CO)2] (0.1 mol%),
L6 (0.2 mol%), pyrrolidine (5 mol%), and benzoic acid (5 mol%), CO/H2 (10 bar), sol-
vent (2 mL), 658C, 24 h. [b] Conversion based on 1a and determined by GC analy-
sis. [c] Yield determined by GC analysis; the ratios of E to Z isomers were deter-
mined by GCMS analysis.
uct 5aa is observed over the period of 10 h. In agreement
with domino-hydroformylation/homoaldol condensation reac-
tion vide supra (Figure 1), hydroformylation of 1-octene 1a is
also established as a rate-determining step in this domino-hy-
droformylation/cross-aldol condensation reaction.
aldol byproducts are less than 5% according to GC analysis.
Finally, we were interested in demonstrating the usefulness
of our procedure for the synthesis of industrially relevant fine
chemicals. Hence, the synthesis of 6 was performed, which is
a very popular fragrance sub-
stance for creating jasmine
notes in the fragrance indus-
try.[24] The product is stable to
alkali and long-lasting and large
quantities are used, particularly
in soap perfumes. To our delight,
our domino sequence is conven-
iently scaled up to a 50 mmol
scale resulting in a 94% yield of
Notably, directly using nonanal 2a with benzaldehyde 4a as
a control experiment in the presence of the acid/base
co-catalyst revealed the formation of two equivalents
of the homoaldol products compared to the cross-
aldol product with moderate conversion (based on
nonanal) [Eq. (1)]. In essence, such a general problem
of chemoselectivity can easily be resolved by our
domino-hydroformylation/cross-aldol protocol, pre-
sumably attributed to the low concentration of nona-
nal 2a compared to benzaldehyde 4a during the
course of the reaction. Indeed, the kinetic examina-
tion of the domino-hydroformylation/cross-aldol condensation
of 1-octene 1a with benzaldehyde 4a under the optimal reac-
tion conditions revealed in the first 7 h of the reaction a very
small concentration of nonanal (<1%). As shown in Figure 2,
parallel to the decrease of the concentration of the starting
materials (1-octene 1a and benzaldehyde 4a) an increase of
the desired condensation product 5aa is observed over the
period of 10 h. In agreement with domino hydroformylation/
homoaldol condensation reaction vide supra (Figure 1), hydro-
formylation of 1-octene 1a is also established as the rate-de-
termining step in this domino-hydroformylation/cross-aldol
condensation reaction.
the desired a-amylcinnamaldehyde [Eq. (2)].
Conclusion
Here, we present an efficient and highly selective intermolecu-
lar domino-hydroformylation/aldol reaction sequence that
allows for the synthesis of a,b-unsaturated aldehydes. Various
olefins and aromatic aldehydes underwent efficient transforma-
tion in the presence of a cooperative rhodium/phosphine and
organocatalyst system to afford the corresponding a,b-unsatu-
rated aldehydes in good to excellent yields with high E stereo-
selectivities. For the first time also excellent chemoselectivity is
achieved in intermolecular hydroformylation/cross-aldol con-
densation reactions and the corresponding a,b-unsaturated al-
dehydes were obtained effectively by suppressing the unwant-
ed homoaldol condensation side reactions. Key to success is
With the optimal conditions in hand (Table 4, entry 2), we
examined the generality of the domino-hydroformylation/
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added under an argon atmosphere. The autoclave was pressurized
with 10 bar CO/H2 (1:1) and heated to 658C for 16 h. After the re-
action time, the autoclave was cooled with ice water and the pres-
sure was released. The stereoselectivity was measured by GC analy-
sis of the crude reaction mixture. After removing the solvent by
vacuum, the residue was directly purified by flash chromatography
on silica gel (eluent: heptane/ethyl acetate=30:1) to give the de-
sired product 3 (3j was purified by bulb-to-bulb distillation).
Table 5. Domino-hydroformylation/cross-aldol reaction of 1 with 4.
General procedure for the preparation of 5
A 25 mL Schlenk flask was charged with [Rh(acac)(CO)2] (3.1 mg,
0.1 mol%), Naphos L6 (15.62 mg, 0.2 mol%), pyrrolidine (50 mL,
5 mol%), benzoic acid (73.2 mg, 5 mol%), and NMP (16 mL). A
4 mL glass vial was charged with 4 (1.5 mmol) and a stirring bar
was added. Then, this clear light yellow solution (2 mL) and
1 (1.5 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 argon atmosphere.
After flushing the autoclave three times with nitrogen, the pressure
of CO/H2 (1:1) was increased to 10 bar. The reaction was performed
for 16 h at 658C. After the reaction finished, the autoclave was
cooled to room temperature and the pressure was carefully re-
leased. The stereoselectivity was measured by GC analysis of the
crude reaction mixture. The reaction mixture quenched by water
and extracted with ethyl acetate (3ꢁ15 mL). The combined organic
layer was washed with brine (1ꢁ45 mL) and dried over anhydrous
MgSO4. After the evaporation, the residue was purified by flash
chromatography on silica gel (eluent: heptane/ethyl acetate=30:1)
to give the desired product 5.
Acknowledgements
This work has been funded by Evonik Industries and the BMBF
(Germany). We thank Dr. C. Fischer, S. Buchholz, and S. Scharei-
na for their technical and analytical support. We are grateful to
Dr. A. D. Chowdhury for helpful discussions.
[a] Reaction conditions:
1 (1.5 mmol), 4 (1.5 mol), [Rh(acac)(CO)2]
(0.1 mol%), L6 (0.2 mol%), pyrrolidine (5 mol%), benzoic acid (5 mol%),
CO/H2 (10 bar), NMP (2 mL), 658C, 16 h; yield of isolated product; the
ratios of E to Z isomers were determined by GCMS analysis; cases of 5ad–
ia by using pyrrolidine (15 mol%) and benzoic acid (15 mol%).
Keywords: catalysis · domino reactions · hydroformylation ·
olefins · unsaturated aldehydes
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Our synthetic protocol is straightforward, atom-efficient, and
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A 100 mL steel autoclave was charged under an argon atmosphere
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Chem. Eur. J. 2014, 20, 13210 – 13216
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Full Paper
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Received: April 29, 2014
Published online on September 1, 2014
Chem. Eur. J. 2014, 20, 13210 – 13216
www.chemeurj.org
13216
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim