Regioselective synthesis of β-aryl- and β-amino-substituted aliphatic esters by rhodium-catalyzed tandem double-bond migration/conjugate addition

Article abstract of DOI:10.1002/chem.201100654

Rhodium-phosphite catalysts were found to effectively mediate double-bond migrations within unsaturated esters. Once the double-bond is in conjugation with the carboxylate group, they also catalyze the Michael addition of carbon and nitrogen nucleophiles.

Full text of DOI:10.1002/chem.201100654

DOI: 10.1002/chem.201100654
Regioselective Synthesis of b-Aryl- and b-Amino-Substituted Aliphatic
Esters by Rhodium-Catalyzed Tandem Double-Bond Migration/Conjugate
Addition
Dominik M. Ohlmann,[a] Lukas J. Gooßen,*[a] and Markus Dierker[b]
Abstract: Rhodium–phosphite catalysts
were found to effectively mediate
double-bond migrations within unsatu-
rated esters. Once the double-bond is
in conjugation with the carboxylate
group, they also catalyze the Michael
addition of carbon and nitrogen
nucleoACHTUNGTRENNUNGphiles. In the presence of these
catalysts, unsaturated carboxylates
enter a dynamic equilibrium of posi-
tional and geometrical double-bond
isomers. The conjugated species are
continuously removed through 1,4-ad-
ditions with formation of b-amino
esters or b-arylated products, depend-
ing on the nucleophile employed. The
applicability of both protocols to a
range of substrates, such as fatty esters
of different chain lengths and double-
bond positions, and several nucleo-
philes including arylborates and pri-
mary and secondary amines, is
demonstrated.
À
Keywords: amino acids · C C cou-
pling · conjugate addition · fatty
acids · isomerization
Introduction
In both reactions, inexpensive mixtures of double-bond
isomers are selectively converted into valuable, terminally
functionalized products.
Double-bond migration is often encountered as an unwant-
ed side reaction in metal-catalyzed transformations, for ex-
ample, hydrogenations, hydroformylations, olefin metathe-
ses, and Heck reactions.[1] However, a fast double-bond mi-
gration can also open up new synthetic opportunities when
combined with an irreversible reaction step that selectively
removes certain double-bond isomers from the equilibrium.
This concept of isomerizing functionalizations becomes par-
ticularly advantageous if the double-bond isomer required
for the desired functionalization step is hard to access,
whereas another isomer bearing the double-bond in a differ-
ent position is readily available.[2] It has previously been im-
plemented, for example, in hydroformylations[3] or hydro-
This reaction type has also been utilized for the valoriza-
tion of fatty acid derivatives, which are widely available at
low cost from renewable feedstocks. They can be selectively
functionalized at the terminal position through transition-
metal-catalyzed hydroboration, hydroformylation, or alk-
ACHUTNGRENoNUG xyACHUTNGTRENcNNGU arbonylation. Thus, Angelici et al. reported an isomeriz-
ing hydroboration of fatty esters selectively at the terminal
position in the presence of an iridium catalyst (A,
Scheme 2).[5] Behr et al. described the synthesis of linear al-
ACHTUNGTRENNUNG
aminomethylations[4] of internal olefins by Beller et al.
Scheme 1. Isomerizing hydroaminomethylation or hydroformylation of
internal olefins.
Scheme 2. Examples for isomerizing terminal functionalization reactions.
(Scheme 1).
dehydes from internally unsaturated fatty esters under hy-
droformylation conditions by using a rhodium catalyst bear-
ing a sterically demanding phosphite ligand (B).[6] A palladi-
um-based catalyst system was used to convert olefinic fatty
acids and alcohols into dialkyl dicarboxylates by isomerizing
alkoxycarbonylation (C).[7] The resulting products are of
great interest for bio-based polymers, which have been
named ꢀnatureꢁs polyethyleneꢁ.[8]
[a] D. M. Ohlmann, Prof. Dr. L. J. Gooßen
Fachbereich Chemie, Technische Universitꢂt Kaiserslautern
Erwin-Schrçdinger-Straße 54
67663 Kaiserslautern (Germany)
Fax : (+49)631-205-3921
E-mail: goossen@chemie.uni-kl.de
[b] Dr. M. Dierker
In all these cases, the functional group was introduced se-
lectively at the terminal position of the alkyl chain, taking
Care Chemicals Technology, Cognis GmbH
Henkelstraße 67, 40551 Dꢃsseldorf (Germany)
9508
ꢄ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 9508 – 9519

FULL PAPER
advantage of both the lower electron density and lower
steric hindrance of terminal olefins relative to all other iso-
mers.
We are aware of only one case of an isomerizing function-
alization of fatty acids that takes places selectively at other
chain positions than the w-carbon: In the presence of strong
Brønsted acids, unsaturated fatty acids react with formation
of five- or six-ring lactones.[9] We showed that this transfor-
mation leads exclusively to the five-ring lactones when per-
formed in the presence of a silver triflate catalyst, which
promotes both the double-bond isomerization and the cycli-
zation step (Scheme 3).[10]
Scheme 5. Direct synthesis of b-substituted esters from olefinic carboxyl-
AHCTUNGTERGaNNUN tes.
Table 1. Comparison of catalysts and reaction conditions for the isomeri-
zation of ethyl oleate (1 f).
Catalyst ([mol%])
Solvent
T
Isomerization
[8C] of 1 f
1
2
3
4
N
none
CHCl3
EtOH
n-
70
70
80
none[a]
G
moderate[b]
moderate[b]
Scheme 3. Catalytic isomerizing lactonization.
125 complete[c]
octane
EtOH
In all the above examples of isomerizing functionaliza-
tions, the reactions proceed through statistical mixtures of
double-bond isomers and a single product is obtained
through the capture of one specific double-bond isomer. In
a pure isomerization reaction, the isolation of a single
isomer can only be achieved if the mediator is added in stoi-
chiometric quantitites. Angelici and Shih demonstrated that
monounsaturated esters can be selectively converted into
the corresponding a,b-unsaturated isomers through a stoi-
chiometric formation of iron carbonyl complexes
(Scheme 4).[11]
5
6
7
8
RhCl3·3H2O (2)
80
complete[c]
complete[c]
complete[c]
complete[c]
[Rh
[Rh
[Rh
N
ACHTUNGTRENN(UNG cod)] (1.5)/biphephos (1.5) toluene 90
N
toluene 90
(1.5)
[RhCl
9
N
U
toluene 90
complete[c]
[a] No isomerization observed. [b] Up to five double-bond shifts. [c] Iso-
merization into equilibrium distribution.
double-bond migrations in the presence of ester groups, and
then probed which of the active catalysts also mediates the
addition of carbon nucleophiles to Michael systems.
For the isomerization experiments, ethyl oleate ((Z)-octa-
dec-9-enoate, 1 f) was chosen as the model compound be-
cause the equilibrium state of this process has thoroughly
been studied (Scheme 6).[12]
Scheme 4. Two-step synthesis of a,b-unsaturated esters (R=alkyl).
We herein present a process in which catalytic 1,4-addi-
tions are used to continuously capture isomers bearing the
double bond in conjugation with the carboxylate group from
a dynamic equilibrium of positional and geometrical double-
bond isomers. This reaction type allows the direct synthesis
of b-substituted aliphatic esters from unsaturated carboxylic
esters (Scheme 5).
Scheme 6. Catalytic isomerization equilibrium of ethyl oleate.
The reports include theoretical calculations[13] and chro-
matographic analyses of the double-bond distribution.[14] In
concurrence with these reports, the GC analysis of the equi-
librium mixtures of double-bond isomers obtained was com-
plicated by the almost identical polarities and boiling points
of the products. In the gas chromatogram (Figure 1b), most
of the isomers thus exhibit very similar retention times lead-
ing to a complex pattern of partially overlaid peaks. Howev-
er, the a,b-unsaturated isomer ethyl (E)-octadec-2-enoate
(1i) is detected at a distinctly higher retention time that
allows the quantification of this species relative to the sum
of all isomers.
Results and Discussion
Isomerization studies: In search of a catalyst system that is
capable of promoting both isomerizations and conjugate ad-
ditions, we investigated various homogeneous isomerization
catalysts including [PtCl6(H)2], [Ru(CO)ACHTNUGTRENUNG(PPh3)3]HCl,
[Fe(CO)5], RhCl3·3H2O, and several rhodium(I) complexes
(see Table 1). We first evaluated their activity in catalyzing
Chem. Eur. J. 2011, 17, 9508 – 9519
ꢄ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9509

L. J. Gooßen et al.
tions in the presence of catalytic amounts of a hydrobora-
tion agent,[22] and the isomerization–conjugation of
enones.[23] We were pleased to find that with this catalyst
and ethanol as the solvent, the equilibrium distribution of
ethyl oleate isomers was reached within 1 h at 808C
(Table 1, entry 5) or within 14 h at room temperature at
loadings as low as 0.5 mol%.
As a control experiment, we treated ethyl (Z)-octadec-9-
enoate (1 f) and ethyl (E)-octadec-2-enoate (1i) separately
with 2 mol% RhCl3·3H2O in EtOH at 808C for 30 min and
1
obtained identical gas chromatograms and identical H- and
13C NMR spectra by starting from either isomer. This con-
firms that the product distribution obtained indeed repre-
sents the thermodynamically favored equilibrium mixture.
Remaining drawbacks of the RhCl3·3H2O/EtOH system
are its low solubility in nonpolar solvents and, as we discov-
ered later on, its low functional-group tolerance. We thus
screened further rhodium complexes for isomerization activ-
ity and finally found that the rhodium(I) precursors [Rh-
ACHUTNGREN(NUG acac)CAHTUNGTRNE(NUGN cod)] (acac=acetylacetonate; cod=1,5-cycloocta-
Figure 1. Gas chromatograms of a) pure ethyl oleate and b) the equilibri-
um mixture after 5 min with RhCl3·3H2O (5 mol%) in ethanol.[15]
diene; Table 1, entry 6) and [Rh
showed similarly high isomeriza-
tion activity when combined with
the biphephos ligand,[24] whereas
ACHTUNGTREN(NUGN acac)(CO)2] (entry 7)
Once the equilibrium is reached, the isomer with the
double bond in the 2-position makes up 3.5% of the mix-
ture. This corresponds well with the findings of Angelici
et al.[5] In combination with the characteristic shape of the
chromatogram, the value of this integral was used to evalu-
ate whether equilibrium had been reached.
NMR spectroscopy was used as an independent quantita-
tive technique to analyze the product mixtures. In the
1H NMR spectra, many of the signals overlap, but a few
characteristic patterns can unambiguously be assigned to the
a,b-unsaturated isomer 1i. These include a multiplet at d=
6.93 ppm for the b-proton and doublet at d=5.77 ppm for
the a-proton. Similarly, the 13C NMR spectroscopic signals
the [Rh-
bridged
dimers
R
combined with this ligand re-
quired longer equilibration times
(entries 8 and 9).
The sterically demanding Rh/
biphephos system, which has pre-
viously been employed in isomer-
izing hydroformylations by Behr
et al.,[6] required a longer induc-
tion period than the RhCl3/ethanol system. However, it is
much more active in nonpolar organic solvents and tolerates
the presence of amines—an important feature for the con-
version of nitrogen nucleophiles discussed later. It can be
concluded from these results that among all isomerization
catalysts tested, solely the rhodium systems are potential
catalysts for the envisioned isomerizing functionalizations.
À
À
À
for the CH=CH COO motif of this isomer appear at d=
166.7, 149.4, and 121.1 ppm.
The isomerization studies revealed that [PtCl6(H)2] (Spei-
erꢁs catalyst) in combination with catalytic amounts of a hy-
drosilylation agent (HSiMe2Cl)[16] is not suitable for the iso-
merization of ethyl oleate (1 f) (Table 1, entry 1). The com-
plexes [Ru(CO)ACHTUNGTRENNUNG
(PPh3)3]HCl[17] and PdCl2/ROH[18] shifted
the double bond by up to five positions, but the final equili-
bration mixture was not reached within 16 h reaction time
(entries 2 and 3). Attempts to enhance the activity of either
catalyst by a broad screening of phosphine ligands were un-
successful.
Iron pentacarbonyl, which is known to isomerize function-
alized olefins including unsaturated ethers and esters[19,20] di-
rectly displayed activity for the isomerization of ethyl oleate
(1 f), and the thermodynamic equilibrium distribution of
double-bond isomers was reached within 20 h (Table 1,
entry 4). However, even under forcing conditions (20 mol%
Bifunctional catalysts: The next question we addressed was
whether one of these catalysts could also be used to selec-
tively convert the a,b-unsaturated double-bond isomer pres-
ent in the equilibrium mixture into the desired b-arylated
product. Several literature reports, in which rhodium cata-
lysts mediate the addition of arylboronic acids or aryltri-
fluoroborates to acrylates with formation of b-arylesters,
pointed to the feasibility of this arylation.[25c] However, the
substrate scope of most known catalysts is limited to unsub-
stituted acrylates and does not extend to a,b-unsaturated
esters with long alkyl chains. Tang et al. reported that boron-
ic acids can be added to a,b-unsaturated butenoates by
[Fe(CO)5], 1258C in octane)
a long induction period
(approx. 8 h) was observed.
using a RhCl3/2,2’-bis(diphenylphosphino)-1,1’-binaphthyl
Rhodium
A
(BINAP) system,[26] and Carreira et al. achieved the addition
of boronic acids to cinnamic acid esters with a [RhCl-
diate isomerization–aromatizations,[21] double-bond migra-
9510
www.chemeurj.org
ꢄ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 9508 – 9519

b-Aryl- and b-Amino-Substituted Aliphatic Esters
FULL PAPER
A
The best results were obtained with sodium tetraphenyl-
tivation of potassium aryltrifluoroborates as the aryl source
borate (2a) as the aryl source.[30] By using [Rh
ACTHNGUTRE(NNUG acac)ACHTUNGTRENNUNG(cod)]/
with a cationic rhodium/BINAP catalyst.[27b]
biphephos in a 20:1 toluene/water mixture, the desired prod-
uct 3a was formed in a 73% yield (entry 9). We further opti-
mized the conditions by using 1.5 equivalents of sodium tet-
raphenylborate 2a and finally observed the formation of 3a
in near quantitative yield (entry 10).
We chose the model substrate 1b, in which the conjugated
double bond is substituted with an n-propyl chain, to evalu-
ate the rhodium systems that had shown isomerization activ-
ity (see Table 1). We screened phenylboronic acid, potassi-
um phenyltrifluoroborate, phenylboronic acid MIDA ester
(6-methyl-2-phenyl-1,3,6,2-dioxazaborocane-4,8-dione),
4-
Isomerizing conjugate additions: With a catalyst system at
hand that effectively promotes double-bond isomerizations
and the conjugate addition of a carbon nucleophile to unsa-
turated alkyl carboxylates, the desired tandem double-bond
migration/conjugate addition reaction appeared to be in
close reach.
tolylboroxine, and sodium tetraphenylborate (2a) as aryl
sources under various conditions, including the use of hy-
droxide, fluoride, and phosphate bases. A selection of these
experiments is presented in Table 2.
Indeed, when treating ethyl 5-hexenoate (1a) rather than
1b with sodium tetraphenylborate (2a) under otherwise un-
changed conditions, the b-arylated product 3a was obtained
in reasonable yields along with remaining unsaturated ester
1a as an equilibrium mixture of double-bond isomers
(Table 3, entry 1). Hence, in the presence of this rhodium
catalyst, a dynamic equilibrium of double-bond isomers is
maintained out of which the isomers bearing the double
bond in conjugation with the carboxylate group are con-
stantly removed through conjugate addition.
Table 2. Evaluation of arylboron compounds as carbon nucleophiles.[a]
Cond. Yield [%][b]
À
Ar BX
G
1
2
1.2
1.5
RhCl3·3H2O
RhCl3·3H2O
A
B
1
0
3
4
5
6
7
2.4
2.4
1.2
1.2
1.2
[Rh
[Rh
A
N
R
C
C
C
D
D
8
0
ACHTUNGTRENNUNG
Subsequent systematic studies revealed that the [Rh-
ACHUTNGREN(NUG acac)CAHTUNGTRENN(UGN cod)]/biphephos system is the most effective catalyst
G
53
1
A
E
79[c]
Table 3. Development of the isomerizing conjugate addition reaction.[a]
8
0.7
G
(cod)]2
E
76
9
10
1.0
1.5
[Rh
[Rh
N
G
F
F
73
95
Rh source ([mol%])
2a [equiv] Additive ([equiv]) Yield [%][b]
1
2
3
4
5
6
7
8
9
[Rh
[Rh
A
N
G
–
–
–
–
–
–
–
–
–
–
–
–
65
57
40
18
23
38
0
[a] Reaction conditions: Enoate 1b (0.5 mmol), Rh source (3 mol% Rh),
biphephos ligand (3 mol%), argon atmosphere, conditions A: toluene/
water 1.5:0.5 mL, 808C, 16 h; B: 0.5 equiv KOH, methanol/water
1.8:0.2 mL, 608C, 16 h; C: toluene/water 1.9:0.1 mL, 1108C, 16 h; D:
5 equiv K3PO4, dioxane/water 1.7:0.3 mL, 608C, 16 h; E: 3 equiv KF, tolu-
ene/water 1.5:0.5 mL, 608C, 16 h; F: toluene/water 3.0:0.15 mL, 1008C,
16 h. [b] GC yields were determined by using n-dodecane as the internal
standard. [c] By using 4 mol% of Rh and 4 mol% of ligand.
G
N
R
U
A
1.5
1.5
–
[Rh
[Rh
0[c]
42[d]
10 [Rh
11 [Rh
12 [Rh
13 [Rh
14 [Rh
15 [Rh
16 [Rh
17 [Rh
18 [Rh
19 [Rh
37[e]
0[f]
0[g]
When employing phenylboronic acid as the aryl source in
the presence of hydroxide base, only traces of the desired b-
arylated product 3a were obtained (Table 2, entries 1 and
2). With potassium phenyltrifluoroborate, moderate yields
of up to 53% were obtained by using the [RhClACTHNURGTNEUNG(cod)]2/bi-
phephos system in a toluene/water mixture at 1108C (en-
K2CO3 (1.5)
NEt3 (1.5)
LiOH (1.5)
KF (1.5)
KHF2 (1.5)
TBAB (0.2)
–
7
69
75
39
48
34
95 (89)[h]
tries 3 to 5). The activation of phenylboronic acid MIDA
[a] Reaction conditions: Enoate 1a (0.5 mmol), biphephos ligand
(1.5 mol%) unless stated otherwise, toluene/water 3.0:0.15 mL, 1008C,
20 h, argon atmosphere unless stated otherwise. [b] GC yields were deter-
mined by using n-dodecane as the internal standard. [c] By using 3 mol%
ester[28] was unsuccessful with [Rh
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
biphephos, leading to a 79% yield (entries 6 and 7). A simi-
lar yield was achieved with 4-tolylboroxine[29] in the pres-
of PACHTNUTRGNE(UNG O-allyl)3 as the ligand. [d] By using 1.5 mol% of monophos as the
ligand. [e] By using 1.5 mol% of BINAP as the ligand. [f] Reaction with-
out ligand. [g] Reaction under air. [h] Isolated yield. 1,5-hex=1,5-hexa-
diene; TBAB=tetrabutylammonium bromide.
ence of [RhCl
(entry 8).
ACHTUNGTRENNUNG(cod)]2/biphephos by using a fluoride additive
Chem. Eur. J. 2011, 17, 9508 – 9519
ꢄ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9511

L. J. Gooßen et al.
for this isomerizing conjugate addition reaction (Table 3).
Other rhodium sources that had shown isomerization activi-
ty, including monomeric RhI precursors and bridged dimeric
species, were less effective (Table 3, entries 2 to 6). No con-
version was detected in the absence of rhodium (entry 7).
Among the phosphines tested, the biphephos ligand dis-
played a unique reactivity, whereas other ligands, such as
monophos (3,5-dioxa-4-phospha-cyclohepta[2,1-a:3,4-a’]di-
naphthalen-4-yl)dimethylamine) and BINAP only gave
moderate yields (entries 8 to 10). Further control experi-
ments confirmed the need for ligands (entry 11) and for
inert conditions (entry 12).
We next investigated the influence of bases on the reac-
tion outcome and found that inorganic bases, such as car-
bonate and hydroxide bases, had little effect on the yields
(Table 3, entries 13 to 15). The addition of fluoride salts led
to decreased yields (entries 16 and 17). This seems to indi-
cate that the aryl transfer proceeds smoothly even without a
base (see the mechanistic considerations). Phase-transfer re-
agents did not improve the yields, which indicated that
sodium tetraphenylborate is sufficiently soluble in the tolu-
ene/water mixture (entry 18). Other solvent mixtures, for ex-
ample, chlorobenzene/water or diphenyl ether/water gave
lower or no yields.
late the potassium cation and increase the solubility, we ach-
ieved an improved yield of the chloro-substituted ester 3j of
59%.
Further variations of the aryl group are possible, as shown
for the naphthylated coupling product 3k and the b-(4-tolyl)
ester 3l, which were obtained in yields of 44 and 92%, re-
spectively.
A good yield was achieved for the electron-poor trifluoro-
methyl-substituted tetraarylborate 2e, which gave 70% of
the corresponding b-aryl ester 3m. The methoxy-functional-
ized product 3o was obtained in a reasonable 50% isolated
yield, which showed the compatibility of our protocol with
ether groups.
We also employed heterocyclic aryl nucleophiles, such as
potassium tetrakis(2-thienyl)borate 2g. This substrate gave
only low yields of the desired b-thienyl ester 3m, even in
the presence of crown ether and with higher catalyst load-
ings. We see this as a current limitation of our protocol,
which could be addressed in subsequent studies.
The protocol is not only suitable for reactions on a small
scale, but can easily be scaled up. For example, compound
3a was isolated in 80% yield on a 1.5 g scale.
We also probed whether the relative stability of the
isomer employed as a starting material affects the yield of
the isomerizing conjugate addition. The reaction of ethyl 5-
methyl-5-hexenoate (1j), in which the terminal double bond
is stabilized by a methyl substituent, with 2a furnished the
The yields of the tandem reaction strongly depend on the
amount of sodium tetraphenylborate 2a employed. Best re-
sults were achieved with two equivalents of 2a (entry 19),
leading to the isolation of the b-arylated ester 3a in 89%
yield after purification by column chromatography.
corresponding b-phenyl ester 3o in
a yield of 11%
(Scheme 7). The leftover starting material was present as a
Having thus developed a method for the catalytic isomer-
izing conjugate addition of tetraarylborates to unsaturated
aliphatic esters, we set out to explore the scope of the new
protocol. We chose olefinic substrates of various chain
lengths and double-bond positions (Table 4).
Very good yields were obtained for the terminally unsatu-
rated C5- and C6-esters 1a and 1c. Even for the 10-undece-
noate 1d, in which the double bond has to migrate over
eight positions along the chain and 17 isomers are possible,
we obtained the corresponding product 3d in 63% yield. A
comparably high yield was achieved for the reaction of the
internally unsaturated ester 1e.
The longer the aliphatic chain, the more positional and
geometrical isomers are possible—more than 30 in the
rather extreme case of ethyl oleate (1 f). This substrate,
which is accessible from the renewable feedstock sunflower
oil, was converted to b-phenyloctadecanoate (3 f) in 30%
yield. We see this as a promising result on the way to new
processes that make use of plant oils instead of petrochemi-
cal resources.
Turning our attention to sterically demanding substrates,
such as the isopropyl ester 1g or the a-substituted ester 1h,
the corresponding products 3g and 3j were isolated in yields
of 62 and 45%, respectively.
Usually, the sodium tetraarylborates are more soluble
than the corresponding potassium salts. In the case of aryl-
borate 2b, only the potassium salt was available and gave a
moderate yield of 50%. By adding the [18]crown-6 to che-
Scheme 7. Isomerizing conjugate addition to substituted unsaturated
ester 1j.
mixture of double-bond isomers, which showed that the cat-
alyst, in principle, is able to migrate the double bond away
from the thermodynamically favored 5-position.
This preliminary result shows that such compounds can
also be converted, but further catalyst optimization would
be required to fully extend our concept to such particularly
challenging substrates.
Mechanistic considerations: A plausible mechanistic path-
way leading from the starting material to the arylated prod-
uct includes two cooperating catalytic cycles: one for the
double-bond isomerization (A), the other one for the conju-
gate addition (B). The catalytic double-bond migration
within the unsaturated ester 1 is initiated by coordination of
the C=C bond to the rhodium complex I, forming the
À
adduct II. This intermediate undergoes a C H insertion of
the metal center into the olefinic double bond and rear-
rangement to give a p-allyl rhodiumACTHNUTRGNEUNG(III) species III. This
9512
www.chemeurj.org
ꢄ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 9508 – 9519

b-Aryl- and b-Amino-Substituted Aliphatic Esters
FULL PAPER
Table 4. Scope of the isomerizing conjugate addition of tetraarylborates to olefinic esters.[a]
Ester
Borate
Product
Yield [%][b]
89 (91)
Ester
Borate
Product
Yield [%][b]
56 (59)[d]
NaBPh4
(2a)
KB
N
ACHTUNGTRENNUNG
NaB
(2c)
ACHTUNGTNER(NUNG 2-nap)4
2a
2a
81 (86)
63 (68)
44 (49)
92 (98)
AHCTUNGTRENNUNG
NaB
(2d)
ACHTUNGTRNEN(UNG 4-tolyl)4
AHCTUNGTRENNUNG
NaB(3-CF3C6H4)4
AHCTUNGTERG(NNUN 2e)
2a
2a
60 (68)
70 (94)[c]
KB(2-thienyl)4
AHCTUNGTERG(NNUN 2 f)
30 (31)[c]
(10)[c,d]
NaB(4-MeOC6H4)4
AHCTUNGTERG(NNUN 2g)
2a
2a
62 (65)
45 (51)
50 (56)[c]
[a] Reaction conditions: Enoate 1 (1.0 mmol), tetraarylborate 2 (2.0 mmol), [RhACHTUNTRGENN(UG acac)AHCTUNGTRNEN(UGN cod)] (1.5 mol%), biphephos (1.5 mol%), toluene/water 3.0/
0.15 mL, 1008C, 20 h, argon atmosphere. [b] Isolated yields (numbers in brackets indicate GC yields). [c] 3 mol% of catalyst. [d] With [18]crown-6
(2.0 equiv). 2-nap=2-naphthyl.
hydrido-complex rearranges to intermediate IV by b-hy-
dride elimination, with the double bond shifted by one posi-
tion. The isomerized ester VI is then released from this
complex, replenishing the active species I and closing the
catalytic cycle A.
Scheme 8 illustrates the double-bond migration towards
the carboxy group, which eventually leads to the formation
of the a,b-unsaturated ester VII.
vious from the experiment mentioned above, in which the
two octadecenoate isomers 1 f and 1i—bearing their double
bond in positions 9 or 2, respectively—led to the same equi-
librium distribution of isomers after catalytic double-bond
migration. However, only the isomer with the double bond
in conjugation with the carboxy group can enter the second
catalytic cycle, leading to irreversible functionalization.
Cycle B begins with an activation of the rhodium precur-
sor through ligand exchange of acac with water to form the
rhodium hydroxide IX.[31] The tetraarylborate 2 transfers an
aryl group onto the rhodium center, resulting in complex X
Due to the reversible nature of each step within the iso-
merization process, the double-bond could as well migrate
towards the methyl terminus of the chain. This becomes ob-
Chem. Eur. J. 2011, 17, 9508 – 9519
ꢄ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9513

L. J. Gooßen et al.
al rapidly entered a dynamic
equilibrium of isomers, from
which only the a,b-unsaturated
compounds, now present in
lower concentration, were able
to react with the amine. The
highest yields were achieved in
the
presence
of
[Rh-
AHCTUNGRTENN(GUN acac)(CO)2]/biphephos, which
indicated that this catalyst re-
establishes the equilibrium par-
ticularly fast (entry 10). The re-
action was pushed to comple-
tion when using a larger excess
of the amine to make up for
Scheme 8. Postulated mechanism of the isomerizing conjugate addition. [Rh]=LnRh, X=acac.
Table 5. Catalyst screening for the direct aza-Michael addition.[a]
and release of the corresponding metal hydroxide and triar-
ylborane as side products. The next step involves a conju-
gate addition of the aryl moiety from X to the previously
formed Michael system VII. The resulting rhodium-bound
ester enolate VIII is set free by a water molecule, yielding
the desired product 3 and regenerating the active species
IX.
Entry
Catalyst
–
G
Yield [%][b]
1
2
3
4
5
6
7
8
72
55
48
51
71
69
78
47
27
65
99[c]
Yb
A
Sc
Bi
U
Isomerizing aza-Michael addition: Encouraged by the suc-
cessful combination of isomerization and conjugate addition
of aryl nucleophiles, we investigated whether this concept
can be extended to other nucleophiles. Our first choice was
nitrogen nucleophiles, since an isomerizing aza-Michael ad-
dition would give access to valuable b-amino esters.[32] This
extension was not at all trivial, as both the nitrogen nucleo-
philes themselves and the Lewis acids, commonly used as
catalysts for the conjugate addition of amines to Michael
systems, were likely to interfere with the isomerization cata-
lyst.
Cu
N
AgOTf
RuCl3
RhCl3
9
10
11
[Rh
[Rh
[Rh
N
E
[a] Reaction conditions: Enoate 1j (0.5 mmol), amine 4c (2.0 equiv)
unless stated otherwise, toluene 2.0 mL, 1008C, 20 h, argon atmosphere.
[b] GC yields were determined by using n-dodecane as the internal stan-
dard. [c] 10 equiv of 4c were used.
We first sought for a reliable protocol for the (nonisome-
rizing) conjugate addition of amines to Michael systems. A
variety of Lewis acids, among them Yb
N
the low equilibrium concentration of the a,b-unsaturated
ester (entry 11).
Sc(OTf)3, and Bi(OTf)3, have been reported to catalyze the
A
ACHTUNGTRENNUNG
conjugate addition of primary and secondary amines to un-
substituted acrylates.[33] We used the reaction of the alkyl-
substituted a,b-unsaturated model substrate 1j and pyrroli-
dine (4c) to investigate several catalysts and conditions in
the conjugate addition step (see the scheme in Table 5).
Even in the absence of a catalyst, the desired amino ester
5c formed in 72% yield after 20 h at 1008C (Table 5,
entry 1). The addition of catalytic amounts of Lewis acids,
for example, ytterbium, scandium, bismuth, copper, and
Since the addition product appeared to be formed out of
a dynamic isomerization equilibrium, it should no longer
matter which double bond isomer is used as the starting ma-
terial. Indeed, when we performed the same reaction with
the terminally unsaturated ester 1c under otherwise un-
changed conditions, the desired amino ester 5c was also de-
tected in 99% GC yield. We re-evaluated the other isomeri-
zation catalysts (RhCl3, [Ru(CO)
this reaction, but observed only low yields, confirming that
[Rh(acac)(CO)2]/biphephos is an uniquely effective catalyst
ACHTUGNTRENUN(GN PPh3)3]HCl and PdCl2) for
silver triflates as well as ruthenium
G
ACHTUNGTRENNUNG
have the expected beneficial effect (entries 2 to 7).
for this transformation.
In none of these reactions we observed double-bond iso-
merization of 1j. However, when adding isomerization cata-
lyst to the reaction mixtures, the yields of the addition reac-
tion markedly decreased and a mixture of double-bond iso-
mers of the starting material 1j was detected (Table 5, en-
tries 8 to 10). An interpretation was that the starting materi-
We next set out to explore the scope of the new aza-Mi-
chael addition. As can be seen in Table 6, it extends to a
broad range of nitrogen nucleophiles and unsaturated esters.
Primary amines, such as cyclohexylamine (4a) and n-bu-
tylamine (4b), gave moderate to good yields, and the alicy-
clic amines 4c–e gave good to excellent yields. Functional-
9514
www.chemeurj.org
ꢄ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 9508 – 9519

b-Aryl- and b-Amino-Substituted Aliphatic Esters
FULL PAPER
Table 6. Scope of the isomerizing conjugate addition of nitrogen nucleo-
philes to olefinic esters.[a]
Further test reactions revealed that these addition reac-
tions are not limited to amines as nitrogen nucleophiles, but
can also be extended to lactams, if appropriate co-catalysts
are added. In the presence of cesium fluoride and Si-
AHCTUNGTRENNUNG
(OEt)4,[34] 2-piperidinone (4g) was added to 1c, furnishing
the corresponding b-amido ester 5i. This example suggests
that many extensions of this reaction concept to other nu-
ACHUTNGRENcNUG leoACHTUNGTRENNpUGN hile classes may be possible.
Ester
Product
Yield [%][b]
44 (46)
Conclusion
62 (70)
89 (99)
Overall, isomerizing conjugate additions reactions constitute
a promising concept for the functionalization of unsaturated
aliphatic compounds. In a systematic catalyst development,
effective isomerization catalysts were identified that are
able to establish a dynamic equilibrium of positional and
geometrical double-bond isomers of unsaturated carboxylic
esters. The isomers bearing the double bond in conjugation
with the carboxylate group can be continuously removed by
catalytic conjugate additions to give valuable b-functional-
ized compounds.
74 (82)
71 (86)
Thus, a catalyst system generated in situ from [Rh
ACHTUNGTRENNUNG(acac)-
AHCTUNGTREG(NNNU cod)] and the bulky bidentate phosphite biphephos effi-
ciently catalyzes both the double-bond migration and the
conjugate addition of tetraarylborates to a,b-unsaturated
carboxylic esters. In the presence of these catalysts, a broad
range of unsaturated carboxylic esters can efficiently be con-
verted into b-aryl-substituted aliphatic esters. The initial po-
sition of the double bond is of no relevance for the efficien-
cy of the transformation. However, as the number of possi-
ble double-bond isomers increases with growing chain
length, the concentration of the required a,b-unsaturated
isomer in the equilibrium mixture decreases. Nevertheless,
the desired b-functionalized product was obtained even in
the rather extreme case of ethyl oleate (1 f), which is an im-
portant milestone towards the utilization of this renewable
feedstock as a raw material for functional molecules.
47 (74)
25 (31)
17 (19)
The reaction concept of isomerizing conjugate additions is
not limited to aryl nucleophiles, but was also applied to ni-
trogen nucleophiles, such as primary, secondary aliphatic,
36[c] (40)
and functionalized amines. A [RhACHTNUGRTNE(NUG acac)(CO)2]/biphephos
catalyst proved to be the most efficient for isomerizing aza-
Michael additions of amines to unsaturated esters, giving
access to a broad range of valuable b-amino esters in moder-
ate to good yields. Preliminary tests revealed that the use of
[a] Reaction conditions: Enoate
1
(0.5–1.0 mmol), amines 4a–g
(10.0 equiv) or amide 4i (5.0 equiv), [RhACHTNUGRTNE(NUG acac)(CO)2] (1.5 mol%), biphe-
phos (1.5 mol%), toluene 2.0 mLmmolÀ1, 1008C, 20 h, argon atmosphere.
[b] Isolated yields (numbers in brackets indicate GC yields). [c] By using
CsF (0.15 equiv) and SiACHTUNGTRENNUNG(OEt)4 (1.0 equiv).
CsF/SiACHTUNTGRNE(UNG OEt)4 as a co-catalyst allows an extension of this re-
action to lactams as nucleophiles. We believe that the ap-
plicability of isomerizing conjugate additions is in no way
limited to the examples presented herein, but will soon be
extended to various other nucleophiles.
ized piperidine derivatives, such as 4 f, were also successfully
converted.
Even the terminally unsaturated ester 1d with its 17 possi-
ble double-bond isomers gave a remarkable yield of 25% of
the b-aminoester 5g. By starting from ethyl oleate (1 f) with
33 possible isomers, significant quantities of b-aminostearate
5h were generated.
Experimental Section
General methods: Reactions were performed under an argon atmosphere
in oven-dried glassware containing a Teflon-coated stirrer bar and dry
Chem. Eur. J. 2011, 17, 9508 – 9519
ꢄ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9515

L. J. Gooßen et al.
septum. For the exclusion of atmospheric oxygen from the reaction
media, solvents were degassed by 45 min argon sparging before the re-
agents were mixed. Solvents were purified by standard procedures prior
to use. All reactions were monitored by GC analysis by using n-dodecane
as an internal standard. Response factors of the products with regard to
n-dodecane were obtained experimentally by analyzing known quantities
of the substances. GC analyses were carried out by using an HP-5 capilla-
ry column (phenyl methyl siloxane 30 mꢅ320ꢅ0.25, 100/2.3–30–300/3)
matography (SiO2, diethyl ether/hexane 1:8) yielded 3g as a colorless
liquid (145 mg, 62%). 1H NMR (600 MHz, CDCl3): d=7.26–7.31 (m,
2H) 7.17–7.21 (m, 3H) 4.91 (dt, J=12.5, 6.2 Hz, 1H) 3.07–3.14 (m, 1H)
2.51–2.63 (m, 2H) 1.58–1.65 (m, 2H) 1.13–1.28 (m, 5H) 1.06 (d, J=
6.4 Hz, 3H) 0.87 ppm (t, J=7.3 Hz, 3H); 13C NMR (151 MHz, CDCl3):
d=171.9, 144.0, 128.2, 127.5, 126.2, 67.3, 42.1, 38.5, 21.6, 21.6, 20.4,
13.9 ppm; MS (Ion trap, EI): m/z (%): 235 [M+] (13), 191(16), 132 (94),
117 (32), 107 (58), 91 (100), 43 (33); HRMS (EI): m/z: calcd for
C15H22O2: 234.1620; found: 234.1609; IR (NaCl): n˜ =3083 (w), 2977 (s),
1729 (vs), 1493 (m), 1453 (s), 1260 (s), 1108 cmÀ1 (vs).
and
a time program beginning with 2 min at 608C, followed by
308CminÀ1 ramp to 3008C, then 3 min at this temp. Column chromatog-
raphy was performed by using a Combi Flash Companion-Chromatogra-
phy-System (Isco-Systems) and RediSep packed columns (12 g). TLC
analyses were performed on commercial 60 F254 silica gel plates. NMR
spectra were obtained on Bruker AMX 200, AMX 400 or on Bruker
Avance 600 systems by using CDCl3 as the solvent, with proton and
carbon resonances at 200, 400, or 600 MHz and 51, 101, or 151 MHz, re-
spectively. Mass spectral data were acquired on a GCMS Saturn 2100 T
(Varian). HRMS were taken on a GCT Premier (Waters). IR spectra
were measured on a Perkin–Elmer FTIR. Bands are given in cmÀ1 with
intensities (vs very strong, s strong, m medium, w weak). Commercial
substrates were used as received unless otherwise stated. Noncommercial
olefinic esters 1 were synthesized from the corresponding acids by using
standard esterification methods. Noncommercial arylborates 2 were syn-
thesized by following a literature procedure.[35]
Ethyl 3-(4-chlorophenyl)hexanoate (3j): Compound 3j was synthesized
by following the general procedure from ethyl 5-hexenoate (1a)
(75.0 mg, 1.0 mmol) and potassium tetrakis(4-chlorophenyl)borate (2b)
(1100 mg, 2.0 mmol) with addition of [18]crown-6 (529 mg, 2.0 equiv). Pu-
rification by flash column chromatography (SiO2, diethyl ether/hexane
1:9) yielded 3j as a colorless liquid (144 mg, 56%). 1H NMR (400 MHz,
CDCl3): d=7.28 (m, 2H) 7.15 (m, 2H) 4.05 (q, J=7.2 Hz, 2H) 3.07–3.16
(m, 1H) 2.50–2.67 (m, 2H) 1.51–1.70 (m, 2H) 1.13–1.23 (m, 5H)
0.88 ppm (t, J=7.3 Hz, 3H); 13C NMR (101 MHz, CDCl3): d=172.1,
142.6, 131.9, 128.8, 128.4, 60.2, 41.7, 41.4, 38.3, 20.3, 14.1, 13.9 ppm; MS
(Ion trap, EI): m/z (%): 254 [M+] (10), 208 (21), 169 (82), 166 (75), 145
(44), 125 (100), 103 (52); HRMS (EI): m/z: calcd for C14H19O2Cl:
254.1074; found: 254.1069; IR (NaCl): n˜ =2959 (s), 1733 (vs), 1491 (s),
1164 cmÀ1 (s).
General procedure for the isomerizing conjugate addition reaction of ar-
ylborates (Table 4): An oven-dried 20 mL crimp top vial was charged
with acetyl-acetonato(1,5-cyclooctadiene)rhodium(I) (1.5 mol%), biphe-
phos (1.5 mol%), tetraarylborate salt (2.0 equiv), and a stir bar, sealed
with a Teflon septum and evacuated-purged with argon three times. Sub-
sequently, toluene (3 mLmmolÀ1 ester), olefinic ester 1 (0.5–1.0 mmol),
and water (150 mLmmolÀ1 ester) were added by a hypodermic syringe,
and the reaction mixture was stirred for 20 h at 1008C. After cooling to
208C, the solvent was removed in vacuo and ester 3 was obtained after
flash column chromatography (SiO2, ethyl acetate/hexane or diethyl
ether/hexane).
Ethyl 3-(2-naphthyl)hexanoate (3k): Compound 3k was synthesized by
following the general procedure from ethyl 5-hexenoate (1a) (75.0 mg,
0.5 mmol) and sodium tetrakis(2-naphthyl)borate (2c) (541 mg,
1.0 mmol). Purification by flash column chromatography (SiO2, diethyl
1
ether/hexane 1:8) yielded 3k as a colorless liquid (59 mg, 44%). H NMR
(400 MHz, CDCl3): d=7.78–7.89 (m, 3H) 7.67 (s, 1H) 7.35–7.53 (m, 3H)
4.05 (qt, J=7.1, 3.5 Hz, 2H) 3.28–3.38 (m, 1H) 2.65–2.79 (m, 2H) 1.74
(q, J=7.8 Hz, 2H) 1.11–1.37 (m, 5H) 0.86–0.97 ppm (m, 3H); 13C NMR
(101 MHz, CDCl3): d=172.4, 141.6, 133.4, 132.3, 128.0, 127.6, 127.5,
126.1, 125.8, 125.7, 125.2, 60.2, 42.1, 41.8, 38.3, 20.5, 14.0, 13.9 ppm; MS
(Ion trap, EI): m/z (%): 270 [M+] (66), 196 (47), 185 (75), 168 (22), 154
(29), 141 (100), 115 (18); HRMS (EI): m/z: calcd for C18H22O2: 270.1620;
found: 270.1613; IR (NaCl): n˜ =2957 (s), 1731 (vs), 1369 (m), 1154 cmÀ1
(m).
Ethyl 3-phenyldecanoate (3e): Compound 3e was synthesized by follow-
ing the general procedure from ethyl trans-4-decenoate (1e) (204 mg,
1.0 mmol) and sodium tetraphenylborate (2a) (686 mg, 2.0 mmol). Purifi-
cation by flash column chromatography (SiO2, diethyl ether/hexane 1:9)
yielded 3e as a colorless liquid (166 mg, 60%). 1H NMR (400 MHz,
CDCl3): d=7.25–7.33 (m, 2H) 7.16–7.23 (m, 3H) 4.03 (q, J=7.0 Hz, 2H)
3.05–3.13 (m, 1H) 2.59 (qd, J=14.8, 7.6 Hz, 2H) 1.63 (ddd, J=14.8, 9.1,
5.9 Hz, 2H) 1.19–1.33 (m, 9H) 1.14 (t, J=7.0 Hz, 4H) 0.86 ppm (t, J=
6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3): d=172.4, 144.2, 128.3, 128.2,
127.6, 127.4, 126.3, 60.1, 42.2, 41.9, 36.2, 31.8, 29.4, 29.1, 27.3, 22.6, 14.1,
14.0 ppm; MS (Ion trap, EI): m/z (%): 277 [M+] (2), 230 (14), 188 (74),
135 (58), 118 (68), 104 (100), 91 (82); HRMS (EI): m/z: calcd for
C18H28O2: 276.2089; found: 276.2091; IR (NaCl): n˜ =3083 (w), 2925 (vs),
2855 (s), 1735 (s), 1453 (m), 1158 cmÀ1 (m).
Ethyl 3-(4-tolyl)hexanoate (3l): Compound 3l was synthesized by follow-
ing the general procedure from ethyl 5-hexenoate (1a) (75.0 mg,
0.5 mmol) and sodium tetrakisACTHUNRTGNEUNG(4-tolyl)borate (2d) (397 mg, 1.0 mmol).
Purification by flash column chromatography (SiO2, diethyl ether/hexane
1:8) yielded 3l as a colorless liquid (109 mg, 92%). 1H NMR (600 MHz,
CDCl3): d=7.09 (q, J=8.2 Hz, 4H) 4.01–4.08 (m, 2H) 3.05–3.10 (m, 1H)
2.52–2.63 (m, 2H) 2.32 (s, 3H) 1.54–1.66 (m, 2H) 1.13–1.24 (m, 5H)
0.86 ppm (t, J=7.3 Hz, 3H); 13C NMR (151 MHz, CDCl3): d=172.6,
141.1, 135.7, 129.0, 127.3, 60.1, 41.9, 41.5, 38.4, 21.0, 20.4, 14.1, 13.9 ppm;
MS (Ion trap, EI): m/z (%): 235 [M+] (22), 182 (100), 167 (49), 149 (76),
115 (25), 105 (95), 91 (23); HRMS (EI): m/z: calcd for C15H22O2:
234.1620; found: 234.1618; IR (NaCl): n˜ =2957 (s), 1735 (vs), 1256 (w),
1162 cmÀ1 (m).
Ethyl 3-phenyloctadecanoate (3 f): Compound 3 f was synthesized by fol-
lowing the general procedure from ethyl oleate (1 f) (98% purity,
158 mg, 0.5 mmol) and sodium tetraphenylborate (2a) (343 mg,
1.0 mmol). Combination of two identical reactions and purification by
flash column chromatography (SiO2, diethyl ether/hexane 1:9) yielded 3 f
as a colorless, low-melting solid (118 mg, 30%). M.p. <308C; 1H NMR
(400 MHz, CDCl3): d=7.26–7.33 (m, 2H) 7.16–7.23 (m, 3H) 4.03 (q, J=
7.2 Hz, 2H) 3.04–3.13 (m, 1H) 2.59 (qd, J=14.8, 7.7 Hz, 2H) 1.58–1.67
(m, 2H) 1.19–1.33 (m, 25H) 1.14 (t, J=7.2 Hz, 4H) 0.89 ppm (t, J=
6.6 Hz, 3H); 13C NMR (101 MHz, CDCl3): d=172.4, 144.2, 128.3, 127.4,
126.3, 60.1, 42.2, 41.9, 36.2, 31.9, 29.7, 29.7, 29.6, 29.6, 29.6, 29.5, 29.4,
29.3, 27.3, 22.7, 14.2, 14.1 ppm; MS (Ion trap, EI): m/z (%): 301 (58), 177
(21), 135 (43), 117 (35), 104 (100), 91 (68); HRMS (EI): m/z: calcd for
C26H44O2: 388.3341; found: 388.3349; IR (KBr): n˜ =3083 (w), 2923 (vs),
2851 (s), 1733 (s), 1457 (w), 1168 cmÀ1 (m).
Ethyl 3-(3-trifluoromethylphenyl)hexanoate (3m): Compound 3m was
synthesized by following the general procedure from ethyl 5-hexenoate
(1a) (75.0 mg, 0.5 mmol) and sodium tetraphenylborate (2a) (343 mg,
1.0 mmol). Purification by flash column chromatography (SiO2, ethyl ace-
tate/hexane 1:9) yielded 3m as
a colorless liquid (101 mg, 70%).
1H NMR (400 MHz, CDCl3): d=7.35–7.51 (m, 4H) 4.02 (q, J=7.15 Hz,
2H) 3.14–3.23 (m, 1H) 2.51–2.70 (m, 2H) 1.56–1.71 (m, 2H) 1.17–1.31
(m, 2H) 1.12 (t, J=7.15 Hz, 3H) 0.84–0.90 ppm (m, 3H); 19F NMR
(376 MHz, CDCl3): d=À62.55 ppm (s); 13C NMR (101 MHz, CDCl3):
d=171.9 (s, 1C), 145.1 (s, 1C), 130.9 (d, J=1.85 Hz, 1C), 130.1–131.1 (m,
1C), 128.8 (s, 1C), 124.2 (q, J=3.70 Hz, 1C), 123.2–123.4 (m, 1C), 124.2
(q, J=271.80 Hz, 1C), 60.3 (s, 1C), 41.9 (s, 1C), 41.5 (s, 1C), 38.3 (s, 1C),
20.4 (s, 1C), 14.0 (s, 1C), 13.8 ppm (s, 1C); MS (Ion trap, EI): m/z (%):
288 [M+] (4), 242 (14), 199 (53), 186 (48), 175 (38), 172 (41), 159 (100),
88 (61); IR (NaCl): n˜ =2960 (m), 1737 (s), 1327 (vs), 1126 cmÀ1 (vs).
Isopropyl 3-phenylhexanoate (3g): Compound 3g was synthesized by fol-
lowing the general procedure from isopropyl 5-hexenoate (1g) (82.2 mg,
0.5 mmol) and sodium tetraphenylborate (2a) (343 mg, 1.0 mmol). Com-
bination of two identical reactions and purification by flash column chro-
Ethyl 3-(4-methoxyphenyl)hexanoate (3o): Compound 3o was synthe-
sized by following the general procedure from ethyl 5-hexenoate (1a)
9516
www.chemeurj.org
ꢄ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 9508 – 9519

b-Aryl- and b-Amino-Substituted Aliphatic Esters
FULL PAPER
(75.0 mg, 0.5 mmol) and sodium tetrakis(4-methoxyphenyl)borate (2g)
(462 mg, 1.0 mmol). Purification by flash column chromatography (SiO2,
ethyl acetate/hexane 1:10) yielded 3m as a colorless liquid (56 mg, 50%).
1H NMR (400 MHz, CDCl3): d=7.10 (m, J=8.61 Hz, 2H) 6.83 (m, J=
8.61 Hz, 2H) 4.03 (q, J=7.04 Hz, 2H) 3.78 (s, 3H) 3.06 (t, J=6.65 Hz,
1H) 2.48–2.63 (m, 2H) 1.50–1.65 (m, 2H) 1.11–1.25 (m, 5H) 0.82–
0.91 ppm (m, 3H); 13C NMR (101 MHz, CDCl3): d=172.5, 157.9, 136.1,
128.3, 113.6, 60.1, 55.1, 42.0, 41.1, 38.5, 20.4, 14.1, 13.9 ppm; MS (Ion
trap, EI): m/z (%): 250 [M+] (26), 207 (43), 165 (85), 134 (19), 121 (100),
91 (16), 77 (9); IR (NaCl): n˜ =2956 (s), 1734 (s), 1513 (s), 1248 cmÀ1 (s).
(70), 184 (80), 156 (26), 126 (100), 110 (10), 96 (16), 42 (12); HRMS (EI):
m/z: calcd for C12H23NO2: 213.1729; found: 213.1742; IR (NaCl): n˜ =
2931 (vs), 1735 (vs), 1158 cmÀ1 (s).
Ethyl 3-(4-methylpiperidin-1-yl)pentanoate (5e): Compound 5e was syn-
thesized by following the general procedure from ethyl 4-pentenoate (1c)
(131 mg, 1.0 mmol) and 4-methylpiperidine (4e) (1012 mg, 1205 mL,
10.0 mmol). Purification by flash column chromatography (SiO2, diethyl
ether/hexane 1:1) yielded 5e as
a colorless liquid (162 mg, 71%).
1H NMR (400 MHz, CDCl3): d=4.10 (q, J=7.0 Hz, 2H) 2.88 (quin, J=
6.9 Hz, 1H) 2.68 (t, J=10.8 Hz, 2H) 2.47 (dd, J=14.1, 6.7 Hz, 1H) 2.08–
2.29 (m, 3H) 1.45–1.66 (m, 3H) 1.21–1.35 (m, 5H) 1.04–1.18 (m, 2H)
0.84–0.96 ppm (m, 6H); 13C NMR (101 MHz, CDCl3): d=173.4, 63.3,
60.1, 49.5, 47.9, 35.3, 34.9, 34.9, 31.3, 23.8, 22.0, 14.2, 11.4 ppm; MS (Ion
trap, EI): m/z (%): 228 [M+] (94), 198 (85), 170 (14), 140 (100), 110 (26),
42 (14); HRMS (EI): m/z: calcd for C13H26NO2: 227.1885; found:
227.1873; IR (NaCl): n˜ =2921 (vs), 1735 (vs), 1166 cmÀ1 (m).
General procedure for the isomerization–conjugate addition reaction of
amines (Table 6): An oven-dried 20 mL crimp top vial was charged with
(acetylacetonato)dicarbonylrhodium(I) (1.5 mol%), biphephos (1.5
mol%), and a stir bar, sealed with a Teflon septum and evacuated-
purged with argon three times. Subsequently, toluene (2 mLmmolÀ1
ester), olefinic ester 1 (0.5–1.0 mmol), and the amine (4) (10.0 equiv)
were added by hypodermic syringe, and the reaction mixture was stirred
for 20 h at 1008C. After cooling to RT, the solvent was removed in vacuo
and b-amino ester 5 was obtained after flash column chromatography
(SiO2, ethyl acetate/hexane or diethyl ether/hexane).
Ethyl 3-(4-carboxyethylpiperidin-1-yl)pentanoate (5 f): Compound 5 f
was synthesized by following the general procedure from ethyl 4-pente-
noate (1c) (131 mg, 1.0 mmol) and ethyl isonipecotate (4 f) (1604 mg,
1573 mL, 10.0 mmol). Purification by flash column chromatography (SiO2,
diethyl ether/hexane 1:1) yielded 5 f as a colorless liquid (135 mg, 47%).
1H NMR (400 MHz, CDCl3): d=4.04–4.14 (m, 4H) 2.88 (quin, J=
7.0 Hz, 1H) 2.68–2.78 (m, 2H) 2.42 (dd, J=14.1, 7.0 Hz, 1H) 2.14–2.29
(m, 4H) 1.76–1.87 (m, 2H) 1.46–1.68 (m, 3H) 1.17–1.34 (m, 7H)
0.86 ppm (t, J=7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3): d=175.2,
173.1, 63.3, 60.1, 48.3, 47.3, 41.6, 35.5, 28.8, 23.5, 14.2, 14.1, 11.4 ppm; MS
(Ion trap, EI): m/z (%): 286 [M+] (22), 257 (15), 256 (100), 210 (57), 199
(22), 170 (31), 55 (20); HRMS (EI): m/z: calcd for C15H27NO4: 285.1940;
found: 285.1952; IR (NaCl): n˜ =2935 (vs), 1733 (s), 1375 cmÀ1 (m).
Ethyl 3-(cyclohexylamino)pentanoate (5a): Compound 5a was synthe-
sized by following the general procedure from ethyl 4-pentenoate (1c)
(131 mg, 1.0 mmol) and cyclohexylamine (4a) (992 mg, 1145 mL,
10.0 mmol). Purification by flash column chromatography (SiO2, diethyl
ether/hexane 1:1) yielded 5a as
a colorless liquid (100 mg, 44%).
1H NMR (400 MHz, CDCl3): d=4.12 (q, J=7.0 Hz, 2H) 3.00 (quin, J=
6.1 Hz, 1H) 2.28–2.51 (m, 3H) 1.83 (d, J=11.0 Hz, 2H) 1.70 (d, J=
12.9 Hz, 2H) 1.58 (d, J=11.7 Hz, 1H) 1.44 (tq, J=14.2, 6.9 Hz, 2H)
1.14–1.30 (m, 6H) 0.97–1.09 (m, 2H) 0.89 ppm (t, J=7.4 Hz, 3H);
13C NMR (101 MHz, CDCl3): d=172.7, 60.2, 53.6, 52.8, 39.7, 34.1, 34.0,
27.7, 26.1, 25.1, 14.2, 10.0 ppm; MS (Ion trap, EI): m/z (%): 228 [M+]
(100), 198 (37), 184 (16), 140 (38), 110 (21), 96 (20), 55 (20); HRMS (EI):
m/z: C13H25NO2 requires 227.1885; found: 227.1869; IR (NaCl): n˜ =2927
(vs), 1731 (s), 1178 cmÀ1 (m).
Ethyl 3-(pyrrolidin-1-yl)undecanoate (5g): Compound 5g was synthe-
sized by following the general procedure from ethyl 10-undecenoate (1d)
(224 mg, 255 mL, 1.0 mmol) and pyrrolidine (4c) (718 mg, 830 mL,
10.0 mmol). Purification by flash column chromatography (SiO2, diethyl
ether/hexane 1:1) yielded 5g as a colorless, viscous liquid (72 mg, 25%).
1H NMR (600 MHz, CDCl3): d=4.12 (qd, J=7.1, 1.2 Hz, 2H) 2.90 (t, J=
5.6 Hz, 1H) 2.50–2.57 (m, 5H) 2.33 (dd, J=14.8, 7.1 Hz, 1H) 1.72 (dt,
J=6.4, 3.3 Hz, 4H) 1.49–1.55 (m, 1H) 1.40–1.46 (m, 1H) 1.30–1.33 (m,
2H) 1.22–1.29 (m, 13H) 0.86 ppm (t, J=7.0 Hz, 3H); 13C NMR
(151 MHz, CDCl3): d=173.1, 60.2, 59.1, 49.7, 36.9, 32.9, 31.9, 29.9, 29.5,
29.3, 25.6, 23.5, 22.7, 14.2, 14.1 ppm; MS (Ion trap, EI): m/z (%): 285
[M+] (100), 196 (73), 170 (100), 142 (31), 110 (46), 84 (16), 42 (32);
HRMS (EI): m/z: calcd for C17H33NO2: 283.2511; found: 283.2507; IR
(NaCl): n˜ =2955 (vs), 2853 (s), 1733 (s), 1162 cmÀ1 (m).
Ethyl 3-butylaminopentanoate (5b): Compound 5b was synthesized by
following the general procedure from ethyl 4-pentenoate (1c) (131 mg,
1.0 mmol) and n-butylamine (4b) (731 mg, 988 mL, 10.0 mmol). Purifica-
tion by flash column chromatography (SiO2, diethyl ether/hexane 1:1)
yielded 5b as a light-yellow liquid (122 mg, 62%). 1H NMR (400 MHz,
CDCl3): d=4.11 (qd, J=7.1, 1.8 Hz, 2H) 2.82–2.93 (m, 1H) 2.49–2.64 (m,
2H) 2.32–2.43 (m, 2H) 1.29–1.48 (m, 6H) 1.23 (td, J=7.2, 2.0 Hz, 3H)
0.83–0.98 ppm (m, 6H); 13C NMR (101 MHz, CDCl3): d=172.7, 60.2,
56.1, 46.5, 38.8, 32.4, 26.9, 20.4, 14.1, 13.9, 9.9 ppm; MS (Ion trap, EI):
m/z (%): 202 [M+] (100), 172 (29), 126 (13), 114 (39), 70 (20), 57 (22);
HRMS (EI): m/z: calcd for C11H23NO2: 201.1729; found: 201.1730; IR
(NaCl): n˜ =2929 (vs), 1735 (s), 1184 cmÀ1 (m).
Ethyl 3-(pyrrolidin-1-yl)octadecanoate (5h): Compound 5h was synthe-
sized by following the general procedure from ethyl oleate (1 f) (98%
purity, 317 mg, 368 mL, 1.0 mmol) and pyrrolidine (4c) (718 mg, 830 mL,
10.0 mmol). Purification by flash column chromatography (SiO2, diethyl
ether/hexane 1:1) yielded 5h as a colorless, viscous liquid (65 mg, 17%).
1H NMR (600 MHz, CDCl3): d=4.12 (qd, J=7.2, 1.1 Hz, 2H) 2.88–2.93
(m, 1H) 2.55 (s, 4H) 2.52 (d, J=5.7 Hz, 1H) 2.33 (dd, J=14.7, 7.0 Hz,
1H) 1.73 (s, 4H) 1.49–1.56 (m, 1H) 1.40–1.47 (m, 1H) 1.31–1.33 (m, 1H)
1.23–1.30 (m, 28H) 0.87 ppm (t, J=7.0 Hz, 3H); 13C NMR (151 MHz,
CDCl3): d=173.1, 60.2, 59.1, 49.8, 36.9, 32.9, 31.9, 29.9, 29.7, 29.7, 29.6,
29.4, 25.6, 23.5, 22.7, 14.2, 14.1 ppm; MS (Ion trap, EI): m/z (%): 381
[M+] (1), 295 (59), 171 (100), 142 (11), 70 (6), 41 (7); HRMS (EI): m/z:
calcd for C24H47NO2: 381.3607; found: 381.3602; IR (NaCl): n˜ =2923 (vs),
2851 (s), 1737 (m), 1238 (w), 1178 cmÀ1 (w).
Ethyl 3-(pyrrolidin-1-yl)pentanoate (5c): Compound 5c was synthesized
by following the general procedure from ethyl 4-pentenoate (1c)
(131 mg, 1.0 mmol) and pyrrolidine (4c) (718 mg, 830 mL, 10.0 mmol).
Purification by flash column chromatography (SiO2, diethyl ether/hexane
1:1) yielded 5c as a colorless liquid (178 mg, 89%). 1H NMR (600 MHz,
CDCl3): d=4.11 (q, J=7.2 Hz, 2H) 2.82 (ddd, J=12.2, 6.8, 5.4 Hz, 1H)
2.50–2.56 (m, 5H) 2.34 (dd, J=14.7, 7.2 Hz, 1H) 1.70–1.75 (m, 4H) 1.53–
1.59 (m, 1H) 1.50 (dt, J=14.3, 7.1 Hz, 1H) 1.24 (t, J=7.1 Hz, 3H)
0.91 ppm (t, J=7.5 Hz, 3H); 13C NMR (151 MHz, CDCl3): d=173.1,
60.5, 60.2, 50.0, 36.6, 25.5, 23.5, 14.2, 9.9 ppm; MS (Ion trap, EI): m/z
(%): 200 [M+] (33), 170 (59), 142 (39), 112 (100), 96 (14), 70 (14); ele-
mental analysis calcd C 66.2, N 7.03, H 10.62; found: C 66.12, N 6.99, H
10.50; IR (NaCl): n˜ =2965 (vs), 1735 (s), 1154 cmÀ1 (m).
Ethyl 3-(2-oxopiperidin-1-yl)pentanoate (5i): Compound 5i was synthe-
sized by following the general procedure from ethyl 4-pentenoate (1c)
(131 mg, 1.0 mmol) and 2-piperidinone (4g) (506 mg, 5.0 mmol). Purifica-
tion by flash column chromatography (SiO2, ethyl acetate/hexane 1:1)
Ethyl 3-(piperidin-1-yl)pentanoate (5d): Compound 5d was synthesized
by following the general procedure from ethyl 4-pentenoate (1c)
(131 mg, 1.0 mmol) and piperidine (4d) (851 mg, 988 mL, 10.0 mmol). Pu-
rification by flash column chromatography (SiO2, diethyl ether/hexane
1:1) yielded 5d as a colorless liquid (158 mg, 74%). 1H NMR (400 MHz,
CDCl3): d=4.05–4.16 (m, 2H) 2.79–2.89 (m, 1H) 2.34–2.55 (m, 5H)
2.13–2.23 (m, 1H) 1.44–1.57 (m, 5H) 1.19–1.40 (m, 6H) 0.82–0.95 ppm
(m, 3H); 13C NMR (101 MHz, CDCl3): d=173.4, 63.7, 60.0, 49.4, 35.3,
26.5, 24.9, 23.7, 14.2, 11.4 ppm; MS (Ion trap, EI): m/z (%): 214 [M+]
yielded 5i as
a
colorless liquid (82 mg, 36%). 1H NMR (400 MHz,
CDCl3): d=4.64–4.74 (m, 1H) 4.03 (qd, J=7.2, 2.3 Hz, 2H) 3.05–3.17 (m,
2H) 2.46–2.57 (m, 1H) 2.25–2.44 (m, 3H) 1.64–1.76 (m, 4H) 1.44–1.63
(m, 2H) 1.17 (td, J=7.1, 2.5 Hz, 3H) 0.80 ppm (td, J=7.3, 2.2 Hz, 3H);
13C NMR (101 MHz, CDCl3): d=171.2, 169.9, 60.3, 52.4, 42.6, 37.1, 32.4,
24.5, 23.0, 20.7, 14.0, 10.5 ppm; MS (Ion trap, EI): m/z (%): 228 [M+]
(52), 182 (41), 170 (55), 152 (100), 140 (79), 100 (74), 55 (53); HRMS
Chem. Eur. J. 2011, 17, 9508 – 9519
ꢄ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9517

L. J. Gooßen et al.
(EI): m/z: calcd for C12H21NO3: 227.1521; found: 227.1517; IR (NaCl):
n˜ =2959 (vs), 1729 (vs), 1637 (vs), 1294 (s), 1174 cmÀ1 (s).
[13] a) Y. Kubota, Fette Seifen Anstrichm. 1976, 78, 118–123; b) P. van
der Plank, Fette Seifen Anstrichm. 1978, 80, 386–388.
[14] a) R. Laꢇ, E. Ucciani, M. Naudet, Bull. Soc. Chim. Fr. 1969, 3, 793–
797; b) G. Cecchi, R. Cerrato, E. Ucciani, Rev. Fr. Corps Gras 1982,
437–443.
[15] GC analyses were performed on a Perkin–Elmer Autosystem XL
(column: Perkin–Elmer EliteWax crossbond PEG, 60 mꢅ320 mmꢅ
0.25 mm; split 10:1, injector 2508C, nitrogen carrier gas; temperature
Acknowledgements
We thank Cognis GmbH and Nanokat for financial support and Umicore
AG for the donation of chemicals. We wish to thank S. Baader for techni-
cal assistance. D.M.O. thanks the Stiftung der Deutschen Wirtschaft for a
scholarship.
program: starting from 408C, heating to 1808C at a rate of 68minÀ1
heating to 2508C at a rate of 158minÀ1, hold for 15 min).
,
[16] a) A. Behr, J. Pꢆrez Gomes, Eur. J. Lipid Sci. Technol. 2010, 112,
31–50; b) The Chemistry of Organic Silicon Compounds (Eds.: S.
Patai, Z. Rappoport), Wiley-VCH, Weinheim, 1998.
[17] H. Wakamatsu, M. Nishida, N. Adachi, M. Mori, J. Org. Chem.
2000, 65, 3966–3970, and references therein.
[1] For double-bond migrations during hydrogenation, see: a) W. D.
Huntsman, N. L. Madison, S. I. Schlesinger, J. Catal. 1963, 2, 498–
505; b) P. van der Plank, J. Am. Oil Chem. Soc. 1972, 49, 327–332;
for double-bond migrations during hydroformylation, see: c) E. N.
Frankel, S. Metlin, W. K. Rohwedder, I. Wender, J. Am. Oil Chem.
Soc. 1969, 46, 133–138; for double bond-migrations during metathe-
sis, see: d) V. Dragutan, I. Dragutan, J. Organomet. Chem. 2006,
691, 5129–5147; e) B. Alcaide, P. Almendros, A. Luna, Chem. Rev.
2009, 109, 3817–3858; for double-bond migrations during Heck re-
actions, see: f) N. Shezad, A. A. Clifford, C. M. Rayner, Tetrahedron
Lett. 2001, 42, 323–325; g) C. L. Kingsbury, S. J. Mehrman, J. M.
Takacs, Curr. Org. Chem. 1999, 3, 497–555.
[2] a) S. Otsuka, K. Tani in Transition Metals for Organic Synthesis:
Building Blocks and Fine Chemicals (Eds.: M. Beller, C. Bolm),
Wiley-VCH, Weinheim, 2004, pp. 199–209; b) H. M. Colquhoun, J.
Holton, D. J. Thompson, M. V. Twigg, New Pathways for Organic
Synthesis: Practical Applications of Transition Metals, Plenum, New
York, 1984, pp. 173–193; c) for reviews on double-bond migration,
see M. B. Smith, J. March, Marchꢀs Advanced Organic Chemistry,
6th ed., John Wiley & Sons, Hoboken, New Jersey, 2007, p. 767–
772, and references cited therein; d) for isomerization-conjugation
of unsaturated oils, see: J. C. Cowan, Ind. Eng. Chem. 1949, 41, 294–
304.
[3] a) I. Piras, R. Jennerjahn, R. Jackstell, W. Baumann, A. Spannen-
berg, R. Franke, K.-D. Wiese, M. Beller, J. Organomet. Chem. 2010,
695, 479–486, and references cited therein; b) M. Beller, B. Zimmer-
mann, H. Geissler, Chem. Eur. J. 1999, 5, 1301–1305.
[4] a) A. Seayad, M. Ahmed, H. Klein, R. Jackstell, T. Gross, M. Beller,
Science 2002, 297, 1676–1678; b) M. Ahmed, R. P. J. Bronger, R.
Jackstell, P. C. J. Kamer, P. W. N. M. van Leeuwen, M. Beller, Chem.
Eur. J. 2006, 12, 8979–8988.
[5] K. Y. Ghebreyessus, R. J. Angelici, Organometallics 2006, 25, 3040–
3044.
[6] A. Behr, D. Obst, A. Westfechtel, Eur. J. Lipid Sci. Technol. 2005,
107, 213–219.
[18] a) J. Tan, Z. Zhang, Z. Wang, Org. Biomol. Chem. 2008, 6, 1344–
1348; b) for recent applications of Pd hydrides, see D. Gauthier,
A. T. Lindhardt, E. P. K. Olsen, J. Overgaard, T. Skrydstrup, J. Am.
Chem. Soc. 2010, 132, 7998–8009, and references therein.
[19] a) Unsaturated esters and ethers: R. Damico, J. Org. Chem. 1968,
33, 1550–1556; b) Lower olefins: M. A. Schroeder, M. S. Wrighton,
J. Am. Chem. Soc. 1976, 98, 551–558; c) calculation of isomer distri-
butions: T. A. Manuel, J. Org. Chem. 1962, 27, 3941–3945.
[20] a) E. N. Frankel, E. A. Emken, V. L. Davison, J. Am. Oil Chem. Soc.
1966, 43, 307–311; b) for mechanistic investigations, see: K. R.
Sawyer, E. A. Glascoe, J. F. Cahoon, J. P. Schlegel, C. B. Harris, Or-
ganometallics 2008, 27, 4370–4379.
[21] a) P. A. Grieco, N. Marinovic, Tetrahedron Lett. 1978, 19, 2545–
2548; b) for details on the formation of Rh hydrides, see: M. J.
Zacuto, F. Xu, J. Org. Chem. 2007, 72, 6298–6300; c) A. Bakac,
Dalton Trans. 2006, 1589–1596.
[22] T. C. Morrill, C. A. D’Souza, Organometallics 2003, 22, 1626–1629.
[23] a) P. A. Grieco, M. Nishizawa, N. Marinovic, W. J. Ehmann, J. Am.
Chem. Soc. 1976, 98, 7102–7104; b) J. Andrieux, D. H. R. Barton,
H. Patin, J. Chem. Soc. Perkin Trans. 1 1977, 359–363.
[24] For the synthesis of biphephos, see: G. D. Cuny, S. L. Buchwald, J.
Am. Chem. Soc. 1993, 115, 2066–2068.
[25] a) J. Christoffers, G. Koripelly, A. Rosiak, M. Rçssle, Synthesis 2007,
1279–1300; b) T. Hayashi, Bull. Chem. Soc. Jpn. 2004, 77, 13–21;
c) J.-F. Paquin, C. R. J. Stephenson, C. Defieber, E. M. Carreira,
Org. Lett. 2005, 7, 3821–3824; d) K. Fagnou, M. Lautens, Chem.
Rev. 2003, 103, 169–196; e) C. Bolm, J. P. Hildebrand, K. MuÇiz, N.
Hermanns, Angew. Chem. 2001, 113, 3382–3407; Angew. Chem. Int.
Ed. 2001, 40, 3284–3308; f) T. Hayashi, K. Yamasaki, Chem. Rev.
2003, 103, 2829–2844.
[26] G. Zou, J. Guo, Z. Wang, W. Huang, J. Tang, Dalton Trans. 2007,
3055–3064.
[27] a) Review: S. Darses, J.-P. Genet, Eur. J. Org. Chem. 2003, 4313–
4327; b) L. Navarre, M. Pucheault, S. Darses, J.-P. Genet, Tetrahe-
dron Lett. 2005, 46, 4247–4250.
[7] a) C. Jimꢆnez-Rodriguez, G. R. Eastham, D. J. Cole-Hamilton,
Inorg. Chem. Commun. 2005, 8, 878–881; b) C. Jimꢆnez-Rodriguez,
G. R. Eastham, D. J. Cole-Hamilton, Chem. Commun. 2004, 1720–
1721; c) D. Quinzler, S. Mecking, Angew. Chem. 2010, 122, 4402–
4404; Angew. Chem. Int. Ed. 2010, 49, 4306–4308.
[28] D. M. Knapp, E. P. Gillis, M. D. Burke, J. Am. Chem. Soc. 2009, 131,
6961–6963.
[29] L. J. Gooßen, J. Paetzold, Adv. Synth. Catal. 2004, 346, 1665–1668.
[30] For examples of the use of tetraarylborates in rhodium-catalyzed ad-
dition reactions, see: a) M. Ueda, N. Miyaura, J. Organomet. Chem.
2000, 595, 31–35; b) K. Ueura, S. Miyamura, T. Satoh, M. Miura, J.
Organomet. Chem. 2006, 691, 2821–2826; c) J. Chen, J. Chen, F.
Lang, X. Zhang, L. Cun, J. Zhu, J. Deng, J. Liao, J. Am. Chem. Soc.
2010, 132, 4552–4553; d) R. Shintani, Y. Tsutsumi, M. Nagaosa, T.
Nishimura, T. Hayashi, J. Am. Chem. Soc. 2009, 131, 13588–13589.
[31] T. Hayashi, M. Takahashi, Y. Takaya, M. Ogasawara, J. Am. Chem.
Soc. 2002, 124, 5052–5058.
[32] a) T. Nishimura, J. Wang, M. Nagaosa, K. Okamoto, R. Shintani, F.-
Y. Kwong, W.-Y. Yu, A. S. C. Chan, T. Hayashi, J. Am. Chem. Soc.
2010, 132, 464–465, and references cited therein; b) T. N. Salzmann,
R. W. Ratcliffe, B. G. Christensen, F. A. J. Bouffard, J. Am. Chem.
Soc. 1980, 102, 6161–6163; c) M. Pfau, Bull. Soc. Chim. Fr. 1967,
1117–1125, and references therein.
[8] D. J. Cole-Hamilton, Angew. Chem. 2010, 122, 8744–8746; Angew.
Chem. Int. Ed. 2010, 49, 8564–8566.
[9] a) A. Granata, F. Sauriol, A. S. Perlin, Can. J. Chem. 1994, 72, 1684–
1690; b) S. C. Cermak, T. A. Isbell, J. Am. Oil Chem. Soc. 2000, 77,
243–248; c) R. Stern, G. Hillion, FR 1987/2623499, 1987; d) J. S.
Showell, D. Swern, W. R. Noble, J. Org. Chem. 1968, 33, 2697–2704.
[10] a) L. J. Gooßen, D. M. Ohlmann, M. Dierker, Green Chem. 2010,
12, 197–200; b) L. J. Gooßen, D. M. Ohlmann, M. Dierker, T. Lçhl,
EP 22411562, 2009.
[11] K.-C. Shih, R. J. Angelici, J. Org. Chem. 1996, 61, 7784–7792.
[12] a) R. H. Ewell, P. E. Hardy, J. Am. Chem. Soc. 1941, 63, 3460–3465;
b) S. J. Rhoads, J. K. Chattopadhyay, E. E. Waali, J. Org. Chem.
1970, 35, 3352–3358; c) S. J. Rhoads, E. E. Waali, J. Org. Chem.
1970, 35, 3358–3361; d) H. Singer, J. D. Umpleby, Tetrahedron 1972,
28, 5769–5777; e) P. van der Plank, H. J. van Oosten, J. Catal. 1975,
38, 223–230.
9518
www.chemeurj.org
ꢄ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 9508 – 9519

b-Aryl- and b-Amino-Substituted Aliphatic Esters
FULL PAPER
[33] a) Ytterbium triflate: S. Matsubara, M. Yoshioka, K. Utimoto,
Chem. Lett. 1994, 827–830; b) Indium trichloride: T. P. Loh, L.-L.
Wei, Synlett 1998, 975–976; c) Ruthenium trichloride: H. Zhang, Y.
Zhang, L. Liu, H. Xu, Y. Wang, Synthesis 2005, 13, 2129–2136;
d) Bismuth triflate: N. Srivastava, B. K. Banik, J. Org. Chem. 2003,
68, 2109–2114.
[35] T. Alaviuhkola, J. Bobacka, M. Nissinen, K. Rissanen, A. Ivaska, J.
Pursiainen, Chem. Eur. J. 2005, 11, 2071–2080.
Received: March 1, 2011
Revised: May 13, 2011
Published online: July 15, 2011
[34] For the Aza-Michael addition of amides to a,b-unsaturated systems,
see: K. Han Ahn, S. J. Lee, Tetrahedron Lett. 1994, 35, 1875–1878.
Chem. Eur. J. 2011, 17, 9508 – 9519
ꢄ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9519