Ionic Liquid (IL) as an effective medium for the highly efficient hydroacylation reaction of aldehydes with azodicarboxylates

Article abstract of DOI:10.1002/adsc.200800808

The highly efficient hydroacylation reaction of aldehydes with azodicarboxylates has been carried out in the ionic liquid,1-n-butyl-3- methylimi-dazolium bis(trifluoromethanesulfonyl)imide, [BMIM] [NTf₂]. The products were readily separated by

Full text of DOI:10.1002/adsc.200800808

FULL PAPERS
DOI: 10.1002/adsc.200800808
Ionic Liquid (IL) as an Effective Medium for the Highly Efficient
Hydroacylation Reaction of Aldehydes with Azodicarboxylates
Bukuo Ni,a,* Qianying Zhang,a Satish Garre,a and Allan D. Headleya,*
a
Department of Chemistry, Texas A&M University – Commerce, Commerce, TX 75429-3011, USA
Fax : (+1)-903-468-6020; e-mail: bukuo_ni@tamu-commerce.edu or allan_headley@tamu-commerce.edu
Received: December 23, 2008; Published online: April 6, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200800808.
Abstract: The highly efficient hydroacylation reac- to conventional solvents, high yields were achieved
tion of aldehydes with azodicarboxylates has been with aliphatic saturated aldehydes, and the reaction
carried out in the ionic liquid,1-n-butyl-3-methylimi- can be conducted under normal to mild conditions
dazolium
bis(trifluoromethanesulfonyl)imide, without the use of a catalyst.
[BMIM] [NTf2]. The products were readily separated
by extraction from the reaction medium and the
ionic liquid could be recycled up to 8 times and the Keywords: aldehydes; azo compounds; green
yields of the reactions were not affected. Compared chemistry; ionic liquids
Introduction
Carbon-nitrogen bond-forming reactions are without
a doubt one of the most important categories of reac-
tions in organic synthesis.[1] Efforts have been made
to construct such bonds by using polar, radical, and
transition metal-catalyzed reactions.[1] Over the last
few decades, a very efficient reaction, which involves
the use of azodicarboxylates as electrophiles, for the
Figure 1. Hydroacylation strategy for hydrazine imides 3.
formation of carbon-nitrogen bonds, has been success-
fully used for such bond formation reactions. The effi- two conditions are limited in that they often result in
ciency of this reaction is due to the strong electron- low yields and only a narrow scope of the substrates
withdrawing azodicarboxylates, which possess
a
can be used. Recently, Lee et al. reported that a tran-
vacant orbital and also serve as good nucleophilic ac- sition metal catalyst, rhodium acetate, efficiently cata-
ceptors.[1a,b] Although various types of reactions, such lyzed the hydroacylation between aliphatic saturated
as the zwitterion intermediate reactions,[2] the electro- and unsaturated aldehydes with azodicarboxylates
philic a-amination of carbonyl compounds,[3] the C H under mild conditions to provide the hydrazine
À
activation at the a-position of amines and ethers,[4] imides 3 (Figure 1, method C).[7] For this method
and the ene-type reaction with olefins[5] in the pres- however, relatively low yields resulted when aromatic
ence of azodicarboxylates, have been extensively stud- aldehydes were used as the substrates. As a result, the
ied, the hydroacylation reaction with aldehydes has development of simple and efficient reaction condi-
been exploited far less.[6] From the standpoint of atom tions while concomitantly increasing the scope of the
economy, the hydroacylation reaction with direct substrates is desirable.
À
functionalization of aldehydic C H bonds to form a
One aspect of our research involves the use of
variety of hydrazine imides is a highly efficient syn- room temperature ionic liquids (RTILs) for novel re-
thetic methodology (Figure 1). To this end, photolytic actions, without metal catalysts; and we recently de-
conditions (Figure 1, method A) and thermal condi- scribed that the aminohalogenation reaction of a,b-
tions (Figure 1, method B) have been utilized to unsaturated ketones proceeded smoothly in modest to
achieve the formation of product 3.[6] However, these good yields and excellent regio- and stereoselectivity
Adv. Synth. Catal. 2009, 351, 875 – 880
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875

Bukuo Ni et al.
FULL PAPERS
in the ionic liquid [BMIM] [NTf2].[8] During the past
decade, RTILs have received considerable attention
due to their ability to serve as effective reaction
media for a wide variety of organic reactions and also
for their use in other applications in chemistry.[9]
Compared to typical organic solvents, RTILs have
several intriguing properties, including their lack of
measurable vapor pressure, high chemical and ther-
mal stability, non-flammability, and high ionic conduc-
tivity;[10] these properties all serve to facilitate various
chemical transformations when RTILs are used as the
reaction media. Also, the high solubility of many or-
ganic and inorganic compounds in RTILs can in prin-
ciple lead to enhanced rates and improved yields for
reactions.[11] Furthermore, RTILs can be easily recy-
cled, and therefore, they are recognized as potentially
environmentally benign reaction media. In this paper,
we wish to report the hydroacylation reaction of alde-
hydes and azodicarboxylates using the ionic liquid,
[BMIM] [NTf2], as solvent which resulted in high
yields of product 3 (Figure 1, method D). Most impor-
tantly, this transformation is carried out without the
use of a catalyst and is conducted under mild reaction
conditions and the IL is recyclable.
Table 1. Optimization reaction of propionaldehyde 1a with
diisopropyl azodicarboxylate 2a.[a]
Entry Solvent
T [8C] t [h] Yield [%][b]
1
2
3
N
r.t.
r.t.
r.t.
124 40
124
23
<10
90
4
G
18
22
32
96
92
91
92
70
5[c]
6[d]
7[e]
8
3
95
9
10
11
MeOH
MeCN
EtOAc
r.t.
r.t.
r.t.
124
124
124
<10
<10
<10
[a]
Reactions were performed with a 2:1 ratio of 1a and 2a
on a 0.5-mmol scale in 0.5 mL of ionic liquid. [BMIM]=
butylmethylimidazolium.
Isolated yields of pure product.
[BDMIM]=1-butyl-2,3-dimethylimidazolium.
Ratio of 1a/2a=1.5:1.
The ratio of 1a/2a=1:1.
[b]
[c]
[d]
[e]
Results and Discussion
the
reaction
using
ionic
liquid
[BMIM]
[(CF3CF2SO2)2N] as solvent,[14] which has a similar
The hydroacylation reaction of propionaldehyde and molecular composition but a larger anion comparing
diisopropyl azodicarboxylate was selected as the to [BMIM] [(CF3SO2)2N] (Table 1, entry 4 vs. 3). As
model for subsequent screening. As can be seen from expected, the reaction proceeded smoothly to afford
the results summarized in Table 1, the reaction effi- the hydroacylation product 3a in 92% yield at room
ciency was significantly influenced by fine tuning the temperature for 18 h.
anion moiety of the ionic liquids, the ratio of alde-
Recently, the effects that the cation of [BMIM]-
hyde/azodicarboxylate, and the temperature. Among based ionic liquids have on the electron transfer have
the RTILs examined as solvents, 1-n-butyl-3-methyl- been investigated, and it has been suggested that the
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
tionÀ efficiencÀy, compared to the ionic liquids with anion.[15] The question of whether the C-2 proton of
BF4 and PF6 as anions; [BMIM] [NTf2] afforded the the imidazolium cation also affects the hydroacylation
corresponding addition product 3a in 90% yield at reaction for the possible activation of the carbonyl
room temperature after 23 h, compared to lower group via hydrogen bonding with the C-2 proton of
yields and longer reaction times for the other ionic the imidazolium cation and thus plays a role in the re-
liquids (Table 1, entries 1–3).[12] These results indicate action is a good one; but, we found that when 1-
that the nature of the anion plays an important role butyl-2,3-dimethylimidazolium bis(trifluoromethane-
in reactivity and efficiency; this could be attributed to sulfonyl)imide [BDMIM] [NTf2] was used as solvent,
the larger anion [NTf2], which would result in a great- in which the C-2 position of the imidazolium cation
er cation/anion separation, compared to other ILs was substituted with a methyl group, the reaction pro-
with harder anions [BF4] and [PF6].[13] These different ceeded smoothly and afforded comparable results as
properties allow for a more effective interaction be- when [BMIM] [NTf2] was used (Table 1, entry 3 vs.
tween the negative charge of the carbonyl oxygen and entry 5). This indicates that the C-2 proton of the imi-
the cationic portion of the ionic liquid, compared to dazolium cation does not affect the reaction rate.
ILs that contain harder anions; such an interaction as- Noteworthy, when the ratio of aldehyde to azodicar-
À
sists in activating the C H bond of the aldehyde and boxylate (1a/2a) was decreased from 2:1 to 1.5:1 and
a more effective solvent activation of the carbonyl 1:1, the reaction proceeded slower and resulted in a
oxygen. In order to get further insight into the role of lower yield with azodicarboxylate (1a/2a) decreasing
the anion in promoting the reaction, we conducted from 2:1 to 1.5:1 and 1:1 (Table 1, entries 3, 6, and 7).
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Ionic Liquid (IL) as an Effective Medium for the Highly Efficient Hydroacylation
FULL PAPERS
Upon raising the temperature from room temperature tries 6 and 7). In these two examples, the low yields
to 408C, the reaction rate was dramatically increased might be due to an ene-type reaction to generate the
with slightly improved yield, which gave the best opti- bisazodicarboxylates;[16] the same phenomenon was
mal performance for the hydroacylation reaction also observed by Leeꢁs research group using the cata-
(Table 1, entry 8). Conventional organic solvents, such lyst, rhodium acetate.[7a] Those aromatic aldehydes,
as MeOH, CH3CN, and EtOAc, which do not exhibit which contain H and Cl were also good substrates for
similar properties as IL, resulted in poor yields this reaction and afforded the hydroacylation prod-
(Table 1, entries 9–11).
ucts in good yield, although the reaction rate was rel-
Encouraged by these results, we next probed the atively slower (Table 2, entries 8 and 9). On the other
scope of this hydroacylation reaction with a variety of hand, aromatic aldehydes with electron-donoting
aldehydes and azodicarboxylates (Table 2). All reac- OMe and electron-withdrawing NO2 groups gave
tions were carried out simply by mixing the reactants poor yields (Table 2, entries 10 and 11). To broaden
in a one-pot operation system in the ionic liquid, the scope of the reaction, a wide range of azodicar-
[BMIM] [NTf2] at 408C affording the corresponding boxylates 2b–f, including azodicarboxylates containing
hydroacylation products 3b–3r. Typically, different phenyl groups substituted with electron-withdrawing
substituents on the aliphatic aldehydes significantly and electron-donating groups were used in the reac-
influence the reaction rates and chemical yields. For tion with propionaldehyde (Table 2, entries 12–16). In
example, the aliphatic saturated aldehydes 1b–e, with general, hydrogen and other substituents on the
either linear or branched substituents when used in phenyl ring influenced the reaction rate and yield. For
the reaction with diisopropyl azodicarboxylate, afford- example, substrates with the phenyl ring substituted
ed the desired products 3b–e in excellent chemical with H, Cl, and NO2 groups gave the desired products
yields (Table 2, etries 1–4). It was also observed that 3n–p in 85–94% yields (Table 2, entries 13–15);
the substitution pattern of aliphatic saturated alde- whereas, when the phenyl ring contains the electron-
hyde influences the reaction rate. For example, in the donating group OMe, a very poor yield with long re-
case of 3-phenylpropionaldehyde, when a phenyl action time resulted (Table 2, entry 16). In order to
group is present at the g-position of propionaldehyde, further confirm the structure of the hydroacylation
relatively low reaction rate and chemical yield were product, the reaction of cyclopentanecarbaldehyde
observed (Table 2, entry 5). The aliphatic aldehydes 1m and 2d was investigated and gave the hydroacyla-
1g and h with unsaturation either at the terminal or tion product 3r (Table 2, entry 17). The structure of 3r
internal position also provided the desired products was unambiguously determined by an X-ray diffrac-
3g and 3h, respectively, but in low yields (Table 2, en- tion study (Figure 2).[17]
Table 2. Hydroacylation reaction of aldehydes with azobicarboxylates.
Entry
R1
R2
t [h]
Product
Yield [%][a]
1
2
3
4
5
6
7
8
1b n-C4H9
1c (CH3)2CHCH2
1d (CH3)2CH
1e Cyclohexyl
1f PhCH2CH2
1g (cis) n-C5H11-CH=CHCH2CH2
1h CH2=CHCH
1i Ph
1j 4-Cl-C6H4
1k 4-MeO-C6H4
1l 4-NO2-C6H4
1a CH3CH2
1a CH3CH2
1a CH3CH2
1a CH3CH2
1a CH3CH2
1m Cyclopentyl
2a i-Pr
2a i-Pr
2a i-Pr
2a i-Pr
2a i-Pr
2a i-Pr
2a i-Pr
2a i-Pr
2a i-Pr
2a i-Pr
2a i-Pr
2b Et
6
5
1
9
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
98
98
99
99
88
43
40
80
48
48
48
120
168
168
168
1.5
20
20
24
168
2
(CH3)2C
9
69
10
11
12
13
14
15
16
17
<10
<10
94
89
94
85
<10
98
2c Bn
2d 4-ClC6H4CH2
2e 4-NO2C6H4CH2
2f 4-MeOC6H4CH2
2d 4-ClC6H4CH2
[a]
Isolated yields of pure product after column chromatography.
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Conclusions
In conclusion, we have developed an efficient hydroa-
cylation reaction of aldehydes with azodicarboxylates
in the ionic liquid [BMIM] [NTf2], the reaction can
be conducted under convenient and mild conditions
without the special protection of inert gases as well as
in the absence of metal catalysts. The products can be
readily separated by extraction due to the solubility
characteristics of the ionic liquid, and the ionic liquid
can be efficiently recycled 8 times without any signifi-
cant loss of the chemical yield.
Experimental Section
Figure 2. X-ray crystal structure of 3r.
General Remarks
We chose the hydroacylation reaction of isobutyral-
dehyde 1d and diisopropyl azodicarboxylate 2a under
optimized reaction conditions to examine the recycla-
bility of ionic liquid [BMIM] [NTf2]. When the first
cycle of the reaction was completed, the reaction mix-
ture was extracted with ether four times. The ether
solution was combined, concentrated, and purified by
flash chromatography to afford the product 3d. The
ether insoluble ionic liquid [BMIM] [NTf2] was recov-
All reactions were performed in oven-dried vials. All com-
mercially available reagents were purchased from Aldrich
and used without further purification. Flash chromatography
was performed using silica gel (Merck 60, 230–400 mesh).
Typical Procedure for the Hydroacylation Reaction in
Ionic Liquid [BMIM] [NTf2]
ered and dried under vacuum for 1 h and reused for To a stirred solution of aldehyde 1 (1.0 mmol) in ionic liquid
[BMIM] [NTf2] (0.5 mL) was added azodicarboxylate 2
(0.5 mmol). The reaction was stirred at 408C for the time as
indicated in Table 1 and Table 2. The reaction mixture was
extracted with ether for four times (5 mLꢂ4). The ether so-
lution was combined, concentrated, and purified by flash
chromatography on silica gel (hexane:ethyl acetate=4:1) to
afford the product diisopropyl 1-acylhydrazine-1,2-dicarbox-
ylate 3. The ether insoluble ionic liquid [BMIM] [NTf2] was
recovered and dried under vacuum for 1 h and reused for
the next cycle of reaction.
the next cycle of the reaction. The ionic liquid can be
recycled for another 7 times without significant loss of
chemical yield and the ionic liquid (Table 3).
It was described in previous studies that the hydro-
acylation of aldehydes with azodicarboxylate consid-
ered to proceed by a radical intermediate mechan-
ACHTUNGTRENNUNG
ism.[6,7a] We assume that the hydroacylation reaction
in an ionic liquid may still proceed via a radical mech-
anism, and that the ionic liquid plays an important
role in stabilizing the radical transition intermediate
through an ionic solvation effect and facilitating the
addition of the acyl radical intermediate to azodicar-
boxylate to form the hydroacylation product.
Hydroacylation Product 3a:[7a] 1H NMR (400 MHz,
CDCl3): d=6.70 (br, 1H, NH), 5.10–4.92 [m, 2H,
(CH3)2CHO], 2.98–2.87 (m, 2H, CH3CH2), 1.32 [d, J=
7.2 Hz, 6H, (CH3)2CHO], 1.27 [br, 6H, (CH3)2CHO], 1.17
(t, J=7.2 Hz, 3H, CH3CH2); 13C NMR (100 MHz, CDCl3):
d=174.6, 155.1, 152.6, 72.1, 70.3, 30.5, 21.8, 21.7, 8.8.
1
Table 3. Recycling studies of hydroacylation reaction of iso-
butyraldehyde 1d and diisopropyl azodicarboxylate 2a in the
ionic liquid [BMIM] [NTf2].
Hydroacylation Product 3b: H NMR (400 MHz, CDCl3):
d=6.72 (br, 1H, NH), 5.10–4.92 [m, 2H, (CH3)2CH], 2.86–
2.85 (m, 2H, CH3CH2CH2CH2), 1.65 (m, 2H,
CH3CH2CH2CH2), 1.43–1.34 (m, 2H, CH3CH2CH2CH2),
1.32 [d, J=7.2 Hz, 6H, (CH3)2CH], 1.28 [br, 6H,
(CH3)2CH], 0.93 (t, J=7.2 Hz, 3H, CH3CH2CH2CH2);
13C NMR (100 MHz, CDCl3): d=173.9, 155.1, 152.6, 72.0,
70.3, 36.7, 26.8, 26.7, 22.2, 21.8, 21.6, 13.8, 13.6; HR-MS:
m/z=289.1769, calcd. for C13H214N2O5 (M+H)+: 289.1763.
Hydroacylation Product 3c: H NMR (400 MHz, CDCl3):
d=6.72 (br, 1H, NH), 5.09–4.92 [m, 2H, (CH3)2CHO], 2.80
[br, 2H, (CH3)2CHCH2], 2.25–2.13 [m, 1H, (CH3)2CHCH2],
1.32 [d, J=6.0 Hz, 6H, (CH3)2CHO], 1.28 [br, 6H,
(CH3)2CHO], 0.98 [d, J=6.8 Hz, 6H, (CH3)2CHCH2];
13C NMR (100 MHz, CDCl3): d=173.1, 155.1, 152.6, 72.0,
70.3, 45.5, 25.4, 25.2, 22.4, 22.3, 21.8, 21.6; HR-MS: m/z=
311.1590, calcd. for C13H24N2O5 (M+Na)+: 311.1577.
Cycle
Yield [%][a]
Cycle
Yield [%][a]
1
2
3
4
99
95
97
96
5
6
7
8
98
96
96
97
[a]
Isolated yields of pure product after column chromatog-
raphy.
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Ionic Liquid (IL) as an Effective Medium for the Highly Efficient Hydroacylation
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1
Hydroacylation Product 3d: H NMR (400 MHz, CDCl3):
d=6.77 (br, 1H, NH), 5.10–4.92 [m, 2H, (CH3)2CHO],
3.70–3.57 [m, 1H, (CH3)2CH], 1.32 [d, J=6.4 Hz, 6H,
(CH3)2CHO], 1.28 [br, 6H, (CH3)2CHO], 1.20 [d, J=6.4 Hz,
6H, (CH3)2CH]; 13C NMR (100 MHz, CDCl3): d=178.2,
155.2, 152.5, 72.0, 70.2, 34.2, 21.8, 21.6, 19.2, 18.8; HR-MS:
m/z=297.1436, calcd. for C13H24N2O5 (M+Na)+: 297.1421.
Hydroacylation Product 3e:[7a] 1H NMR (400 MHz,
CDCl3): d=6.75 (br, 1H, NH), 5.06–4.86 [m, 2H,
(CH3)2CHO], 3.37–3.27 (m, 1H, cyclohexyl-CH), 1.97–1.82
(m, 2H, cyclohexyl-CH2), 1.80–1.57 (m, 3H, cyclohexyl-
CH2), 1.48–1.35 (m, 2H, cyclohexyl-CH2), 1.27 [d, J=6.4 Hz,
6H, (CH3)2CHO], 1.25–1.10 [m, 9H, (CH3)2CHO and cyclo-
hexyl-CH2]; 13C NMR (100 MHz, CDCl3): d=181.1, 152.6,
72.0, 70.2, 44.0, 42.8, 29.4, 28.8, 25.8, 25.7, 25.6, 25.3, 21.8,
21.6.
Hydroacylation Product 3n: White solid, mp 110–1128C
(ethyl acetate-hexane); 1H NMR (400 MHz, CDCl3): d=
7.34 (br, 10H, ArH), 6.86 (br, 1H, NH), 5.23 (s, 2H,
PhCH2), 5.17 (s, 2H, PhCH2), 2.29 (br, 2H, CH3CH2), 1.16
(t, J=7.2 Hz, 3H, CH3CH2); 13C NMR (100 MHz, CDCl3):
d=174.4, 155.4, 153.0, 135.4, 134.7, 128.8, 128.6, 128.4, 128.1,
69.1, 68.1, 30.5, 8.7; anal. calcd. for C19H20N2O5: C 64.04, H
5.66, N 7.86; found: C 64.22, H 5.68, N 7.72.
Hydroacylation Product 3o: White solid, mp 100–1018C
(ethyl acetate-hexane); 1H NMR (400 MHz, CDCl3): d=
7.20–7.05 (m, 8H, ArH), 6.91 (br, 1H, NH), 5.16 (s, 2H, 4-
ClPhCH2), 5.10 (s, 2H, 4-ClPhCH2), 2.89 (br, 2H, CH3CH2),
1.13 (t, J=7.2 Hz, 3H, CH3CH2); 13C NMR (100 MHz,
CDCl3): d=174.3, 155.2, 152.9, 134.6, 134.4, 133.8, 133.1,
129.5, 128.4, 128.8, 128.6, 68.3, 67.2, 30.5, 8.7; anal. calcd. for
C19H18Cl2N2O5: C 53.66, H 4.27, N 6.59; found: C 53.74, H
4.25, N 6.57.
Hydroacylation Product 3f:[7a] 1H NMR (400 MHz,
CDCl3): d=7.30–7.13 (m, 5H, ArH), 6.71 (br, 1H, NH),
5.06–4.88 [m, 2H, (CH3)2CHO], 3.21 (t, J=8.0 Hz, 2H,
PhCH2CH2), 2.97 (t, J=8.0 Hz, 2H, PhCH2CH2), 1.28 [d,
J=6.0 Hz, 6H, (CH3)2CHO], 1.25 [br, 6H, (CH3)2CHO];
13C NMR (100 MHz, CDCl3): d=172.9, 155.0, 152.5, 140.6,
128.4, 126.1, 72.1, 70.3, 38.6, 30.6, 21.8, 21.6.
1
Hydroacylation Product 3q: H NMR (400 MHz, CDCl3):
d=8.21 (d, J=8.4 Hz, 4H, ArH), 7.51 (d, J=8.4 Hz, 4H,
ArH), 7.02 (br, 1H, NH), 5.35 (s, 2H, 4-NO2PhCH2), 5.31 (s,
2H, 4-NO2PhCH2), 2.94 (br, 2H, CH3CH2), 1.18 (t, J=
7.2 Hz, 3H, CH3CH2); 13C NMR (100 MHz, CDCl3): d=
174.2, 155.2, 152.8, 147.9, 147.8, 142.5, 141.9, 128.2, 128.1,
127.0, 123.9, 123.8, 123.7, 67.5, 66.6, 30.5, 8.7; anal. calcd. for
C19H18N4O9: C 51.12, H 4.06, N 12.55; found: C 51.34, H
4.14, N 12.34.
Hydroacylation Product 3r: White solid, mp 97–988C
(ethyl acetate-hexane); 1H NMR (400 MHz, CDCl3): d=
7.40–7.18 (m, 8H, ArH), 6.83 (br, 1H, NH), 5.17 (s, 2H, 4-
ClPhCH2), 5.11 (s, 2H, 4-ClPhCH2), 3.76–3.60 (m, 1H, cy-
clopentyl-CH), 2.00–1.50 (m, 8H, cyclopentyl-CH2);
13C NMR (100 MHz, CDCl3): d=176.9, 155.3, 152.8, 134.6,
134.4, 133.8, 133.2, 129.5, 128.9, 128.8, 68.3, 67.2, 44.6, 30.2,
25.9; anal. calcd. for C22H22Cl2N2O5: C 56.78, H 4.77, N 6.02;
found: C 56.85, H 4.75, N 5.99.
Hydroacylation Product 3g:[7a] 1H NMR (400 MHz,
CDCl3): d=6.68 (br, 1H, NH), 5.44–5.27 (m, 2H, CH2CH=
CHCH2), 5.06–4.87 [m, 2H, (CH3)2CHO], 2.90 (br, 2H,
CHCH2CH2CO), 2.35 (q, J=7.2 Hz, 2H, CHCH2CH2CO),
2.00 (q, J=6.8 Hz, 2H, n-C4H9CH2CH), 1.36–1.10 [m, 18H,
(CH3)2CHO and CH
3ACTHUGNTREN(NNUG CH2)3CH2], 0.84 [t, J=6.4 Hz, 3H,
CH3A
CHTUNGTRENNUNG
155.0, 152.6, 131.4, 127.4, 72.0, 70.3, 37.0, 31.4, 29.2, 27.1,
22.5, 22.4, 21.8, 21.6, 14.0.
Hydroacylation Product 3h:[7a] 1H NMR (400 MHz,
CDCl3): d=6.58 (br, 1H, NH), 5.80–5.66 (m, 1H, CH2 =
CH), 5.08–4.90 [m, 4H, CH2 =CH and (CH3)2CHO], 2.42
(d, J=7.2 Hz, 2H, CH2 =CHCH2), 1.32–1.16 8 [m, 18H,
(CH3)2C and (CH3)2CHO]; 13C NMR (100 MHz, CDCl3):
d=178.6, 155.6, 153.2, 134.2, 117.9, 72.2, 70.6, 45.5, 44.7,
25.2, 22.0, 21.9, 21.8, 21.7.
Acknowledgements
Hydroacylation Product 3i:[7a] 1H NMR (400 MHz,
CDCl3): d=7.65 (br, 2H, ArH), 7.48 (t, J=7.2 Hz, 1H,
ArH), 7.38 (t, J=7.6 Hz, 2H, ArH), 7.03 (br, 1H, NH),
5.04–4.93 [m, 1H, (CH3)2CHO], 4.90–4.80 [m, 1H,
(CH3)2CHO], 1.26 [t, J=6.4 Hz, 6H, (CH3)2CHO], 1.03 [t,
J=6.4 Hz, 6H, (CH3)2CHO]; 13C NMR (100 MHz, CDCl3):
d=171.2, 155.2, 152.8, 135.2, 131.8, 128.0, 72.4, 70.8, 70.6,
70.4, 22.0, 21.8, 21.6, 21.2.
We are grateful to the Robert A. Welch Foundation (T-1460)
for financial support of this research.
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Hydroacylation Product 3j:[7a] 1H NMR (400 MHz,
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1
Hydroacylation Product 3m: H NMR (400 MHz, CDCl3):
d=6.89 (br, 1H, NH), 4.25 (q, J=7.2 Hz, 2H, CH3CH2O),
4.17 (q, J=7.2 Hz, 2H, CH3CH2O), 2.87 (q, J=6.8 Hz, 2H,
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C13H24N2O5 (M+Na)+: 255.0951.
Adv. Synth. Catal. 2009, 351, 875 – 880
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
879

Bukuo Ni et al.
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AHCTUNGTRENNUNG
lated.[7a]
[17] Crystal data for 3r: C22H22Cl2N2O5, M=465.32, triclinic,
a=5.9282(3), b=13.3115(8), c=15.2091(9) Š, a=1088,
b=938, g=1028, V=1103.87(11) Š3, T=227(2) K,
space group P-1, Z=2, reflections collected/independ-
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681474 contains the supplementary crystallographic
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880
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