Immobilization of diphenylamine-linked bis(oxazoline) ligands and their application in the asymmetric friedel-crafts alkylation of indole derivatives with nitroalkenes

Article abstract of DOI:10.1002/ejoc.200901434

A diphenylamine-linked bis(oxazoline) ligand with trans-diphenyl substitution on the oxazoline rings has been immobilized onto one- to three-generation Frechet-type dendrimers and a C₃-symmetric core structure. The catalytic activities and enantioselectivities of these new ligands were tested in the asymmetric Friedel-Crafts alkylation reactions of indole derivatives with, nitroalkenes. The two types of immobilized ligands exhibited similar enantioselectivities and substrate compatibilities to the free ligand trans-DPBO we reported previously. No dendrimer effect was observed in the kinetic investigation of the Frechet-type dendrimer-immobilized ligands. The in situ recycling of the catalysts was also tested to illustrate the effect of reducing catalyst loading and the efficiency of our system.

Full text of DOI:10.1002/ejoc.200901434

FULL PAPER
DOI: 10.1002/ejoc.200901434
Immobilization of Diphenylamine-Linked Bis(oxazoline) Ligands and Their
Application in the Asymmetric Friedel–Crafts Alkylation of Indole Derivatives
with Nitroalkenes
Han Liu[a] and Da-Ming Du*[a,b]
Keywords: Immobilization / Dendrimers / Heterocycles / Friedel–Crafts reaction / Alkylation
A diphenylamine-linked bis(oxazoline) ligand with trans-di-
ligands exhibited similar enantioselectivities and substrate
phenyl substitution on the oxazoline rings has been immobi- compatibilities to the free ligand trans-DPBO we reported
lized onto one- to three-generation Fréchet-type dendrimers
and a C3-symmetric core structure. The catalytic activities
and enantioselectivities of these new ligands were tested in
the asymmetric Friedel–Crafts alkylation reactions of indole
derivatives with nitroalkenes. The two types of immobilized
previously. No dendrimer effect was observed in the kinetic
investigation of the Fréchet-type dendrimer-immobilized li-
gands. The in situ recycling of the catalysts was also tested
to illustrate the effect of reducing catalyst loading and the
efficiency of our system.
insoluble materials used can be polymers functionalized
with active groups for the ligation of catalysts[2] or inor-
ganic materials such as zeolites and molecular sieves.[3] The
recently developed catalyst immobilization by the self-as-
sembly of ligands, which have been defined as self-sup-
ported catalysts, can also be classified into this category.[4,5]
Compared with the original homogeneous systems, the
heterogeneous systems often show lower reactivity and
sometimes lower selectivity as a result of the slow diffusion
of substrates to the interface to which the catalysts are
linked and unfavourable interactions between the support-
ing materials and the active catalytic centres.
The second category is the immobilization of catalysts
onto soluble macromolecules to maintain the homogeneous
system. This strategy has all the advantages of homogen-
eous systems and the recovery can be facilitated by the ad-
dition of another solvent for the catalysts or by using a
membrane reactor (also known as nanofiltration technol-
ogy).[6] The soluble macromolecules used can be poly(ethyl-
ene glycols) (PEGs) of different molecular weights and
highly branched dendrimer molecules of different sizes. In
contrast to PEGs, which are a mixture of polymers of dif-
ferent chain lengths,[7] dendrimers have well-defined struc-
tures as well as accurate molecular weights. As one impor-
tant type of macromolecules, the application of dendrimers
in catalyst immobilization has been developed by scientists
all over the world.[8] The catalytic centres can be located at
the core of the dendrimer (type I) or on the shell (type II),
as illustrated in Figure 1. The effects of dendrimer structure
(chemical constitution and mode of linking), generation
and the position of the active catalytic centres have been
investigated and summarized. In some homogeneous cata-
lytic systems, especially the core-modified dendrimers, an
Introduction
During the past few decades, the progress in homogen-
eous asymmetric catalysis has changed the state-of-the-art
of organic chemistry.[1] More and more chiral products such
as drug intermediates and materials can be obtained with
high efficiency through the use of chiral coordination cata-
lysts or organocatalysts. However, the wide-spread applica-
tion of asymmetric catalysis on an industrial scale is still
limited due to the relatively high cost of the chiral sources
used in ligand preparation, high catalyst loading (1–10 mol-
% in most cases) and contamination of the products with
heavy metal elements leached from the catalysts. To over-
come the drawbacks of homogeneous asymmetric catalytic
processes, the development of recovery technology for
homogeneous catalysts, which includes the synthesis of re-
coverable catalysts immobilized on suitable supporting ma-
terials and the design of reactors, has attracted the attention
of chemists both in academia and in industry laboratories.[2]
On the basis of the number of phases involved in the
system, the recovery strategies can be classified into two
categories. The first one is the immobilization of catalysts
onto insoluble materials to generate a heterogeneous system
and the use of simple filtration for catalyst recovery. The
[a] Beijing National Laboratory for Molecular Sciences (BNLMS),
College of Chemistry and Molecular Engineering, Peking Uni-
versity,
Beijing 100871, People’s Republic of China
[b] School of Chemical Engineering and Environment, Beijing In-
stitute of Technology,
Beijing 100081, People’s Republic of China
Fax: +86-10-68914985
E-mail: dudm@bit.edu.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200901434.
Eur. J. Org. Chem. 2010, 2121–2131
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2121

H. Liu, D.-M. Du
FULL PAPER
Figure 1. Type I and II dendrimer-immobilized catalysts.
improvement in reactivity can be observed with increasing propriate linkers, such as an alkyne-based structure, triazole
size and generation of the dendritic catalysts. Such a phe- from a click cycloaddition and ether. All the designed link-
nomenon, known as the “positive dendrimer effect”, can be ers were tested in the synthesis of the ligands (Figure 3).
attributed to the formation of a microenvironment, which
improves the substrate concentration surrounding the cata-
lytic centre (concentrator effect), prevents product inhibi-
tion (catalytic pump) and provides better stabilization of
the transition state.[9,10]
The diphenylamine-linked bis(oxazoline) ligands re-
ported by Guiry and co-workers[11] and ourselves[12] have
been successfully applied in the asymmetric Henry reaction
of α-keto esters,[12a,12b] the asymmetric Nozaki–Hiyama–
Kishi reaction of aldehydes,[11b,11d] the asymmetric Michael
addition of nitroethane to nitroalkenes,[12c] the asymmetric
Friedel–Crafts alkylation of different electron-rich heteroar-
omatics with nitroalkenes[11c,12d–12f] and the asymmetric
Figure 2. Design of type I immobilized catalysts.
hydrosilylation of prochiral ketones.[13] Some investigations
have focused on the modification of the electronic effect,[12g]
the rigidity of the ligand skeleton[12g] and the effect of the
ligands without C2 symmetry.[11c] As a rational extension of
our project on the application and modification of diphe-
nylamine-derived chiral ligands, we hoped to facilitate the
immobilization of ligands onto dendritic macromolecules in
both type I and II fashions and to investigate the effect of
the dendrimer structure on the catalytic activity and
enantioselectivity, which is important for the further investi-
gation of catalyst recovery in the membrane reactor system.
Herein, we would like to document our recent research re-
sults.
Results and Discussion
Figure 3. Diphenylamine-linked bis(oxazoline) ligands immobilized
on the Fréchet-type dendrimers and the free ligand trans-DPBO
(2).
At the beginning of the type I ligand immobilization, we
had to choose an appropriate dendrimer system. Because
our ligands are usually used in non-polar solvents such as
The desired G1–3 alcohols 4a–c and benzyl bromides 5a–
toluene (optimized solvent for asymmetric Friedel–Crafts c were synthesized easily from 3,5-dihydroxybenzoic acid
alkylation), the Fréchet-type dendrimer composed of a (3) in three to ten steps in high yields following literature
phenyl benzyl ether substructure, which was first reported procedures (Scheme 1).[16] To facilitate the ligation between
by Fréchet and co-workers in 1990,[14,15] becomes the the ligand part and the dendrimer, a ligation site has to be
proper choice because of its good solubility in toluene and introduced onto the diphenylamine skeleton. Because of the
inert nature. On the basis of this choice, we designed the potential versatile transformations of aryl bromides and io-
ligand structure illustrated in Figure 2. The diphenylamine dides, we tested the monohalogenation reaction. To avoid
skeleton was linked to the dendrimer fragment through ap- the possible oxidation of the oxazoline segment and the
2122
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 2121–2131

Immobilization of Diphenylamine-Linked Bis(oxazoline) Ligands
halogenation of the phenyl groups on the oxazoline ring,
the halogenation was conducted before the oxazoline for-
mation. After several attempts, the monobromination and
-iodination products of dimethyl diphenylamine-2,2Ј-di-
carboxylate (7) were obtained in acceptable yields. The se-
lection of the proper halogenation reagent was critical for
the successful transformation.[17] Other reagents such as
bromine, iodine, NBS, KBr/(NH)2MoO4·H2O did not give
any desired product. From the monosubstituted esters, the
ligands 11a/b with trans-diphenyl substitution on the ox-
azoline rings (the optimized ligand structure in asymmetric
Friedel–Crafts reaction[12e,12f]) were synthesized by saponi-
fication of the ester, acyl chloride formation, β-hydroxy-
amide formation and MeSO2Cl-mediated oxazoline ring-
closure (Scheme 2).
Scheme 2. Synthesis of the Br/I-substituted bis(oxazoline) ligands.
Scheme 1. Synthesis of the dendrimer segments.
Next we tried to introduce a hydroxy group (alcohol or
phenol) onto the ligand by the appropriate transformation
of the bromine or iodine atom (Scheme 3). To our disap-
pointment, the n-BuLi/paraformaldehyde process did not
give the hydroxymethyl-derived ligand and neither did the
Ullmann-type coupling of either of the Br/I-substituted es-
ters and ligands with benzyl alcohol or 4-benzyloxyphenol
show significant conversion at high temperature even after
a long reaction time. Such low reactivity may be attributed
to the coordination of the ester group or oxazoline to the
Cu centre, which deactivates the catalyst.
Scheme 3. Attempts to introduce the hydroxy group onto diphenyl-
amine skeleton.
to the Pd centre as a ligand.[19] Because of the easy prepara-
tion and good reactivity of the Br-substituted ligand 11a in
the coupling reaction, the reaction of the I-substituted li-
gand 11b was not examined (Scheme 4).
A similar phenomenon was also observed in our second
attempt to introduce the alkynyl group by Sonogashira cou-
pling of the Br/I-substituted ligands. When the reaction was
conducted under common conditions using [Pd(PPh3)2Cl2]/
CuI as catalyst, no conversion was observed because of the
deactivation of CuI by the oxazoline fragment. The desired
product 13 was obtained in high yield only when the cop-
per-free Sonogashira coupling condition reported by Yi and
Hua[18] was used. The application of piperidine as base was
Scheme 4. Copper-free Sonogashira coupling of the Br-substituted
critical for the successful coupling reaction as it coordinates ligand 11a with alkyne 12.
Eur. J. Org. Chem. 2010, 2121–2131
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2123

H. Liu, D.-M. Du
FULL PAPER
With the alkynyl-substituted ligand 13 in hand, we tested Table 1. Catalytic activities of immobilized ligands in asymmetric
Friedel–Crafts alkylation of indole with nitrostyrene.[a]
the click [3+2] cycloaddition with the known azide 14[20]
derived from the G1 bromide (Scheme 5). Both the CuI and
RuII catalysts[21] gave very low conversions of the alkyne at
both high and low temperatures, whereas heating the alkyne
and azide in toluene without a catalyst led to an inseparable
mixture.
Entry Catalyst Loading [mol-%] Time [h] Yield[b] [%]
ee[c] [%]
1
2
3
4
5
6
7
8
1a
1b
1c
1c
1c
2
5
5
5
2.5
1
5
24
24
24
48
48
24
48
48
99
95
93
98
71
96
99
96
94
93
93
93
93
95
95
95
Scheme 5. Attempts at the click [3+2] cycloaddition of ligand 13
and azide 14.
2
2
2.5
1
As a result of the success we achieved in the copper-free
Sonogashira coupling reaction in the presence of the bis-
(oxazoline) segment, we turned to the last alkyne-based
linker structure (Scheme 6). The G1–3 bromides 5a–c were
derivatized to the corresponding aryl iodides 6a–c by SN2
reaction with 4-iodophenol in the presence of K2CO3 and
crown ether (Scheme 1). Fortunately, the dendrimer-derived
aryl iodides coupled with alkyne 13 smoothly under the
same reaction conditions used for the synthesis of 13
(Scheme 4). The desired ligands 1a–c (Figure 3) were ob-
tained in moderate-to-good yields after purification by sil-
ica gel column chromatography.
[a] The reactions were conducted on a 0.5 mmol scale when 5 or
2.5 mol-% catalyst loading was used and on a 1.25 mmol scale
when 1 mol-% catalyst loading was used. [b] Isolated yield. [c] De-
termined by HPLC on a Chiralcel OD-H column using n-hexane/
2-propanol (70:30) as eluent.
To gain further information on the catalytic activity, the
rates of reaction under catalysis with 5 mol-% ligands 1a–c
and 2 were measured. The conversion of indole was moni-
tored by HPLC on a C18 column using MeOH/H2O (60:40)
as eluent. The results are summarized in Figure 4. In all
cases, the reaction proceeded rapidly and Ͼ98% conversion
was achieved within 4 h at ambient temperature. The differ-
ences in the reaction rates are negligible. When the loading
of the G3 ligand 1c was decreased to 2.5 and 1 mol-%, the
reaction rates dropped significantly compared with the case
of 5 mol-% loading, as illustrated in Figure 5. Only 96.6
and 92.4% conversions were achieved after 6 h, respectively.
No positive dendrimer effect (enhancement of reaction rate
or enantioselectivity) was observed in our system.
Scheme 6. Synthesis of immobilized ligands by copper-free Sonoga-
shira coupling.
With the desired ligands in hand, their catalytic activities
were investigated by using the asymmetric Friedel–Crafts
alkylation of indole 15a with β-nitrostyrene (16a) as a
model system.[22] The G1–3 catalysts were generated in situ
from 1a–c and Zn(OTf)2 in toluene, as we reported be-
fore.[12d–12f] The catalytic reaction was conducted at –20 °C
for 24–72 h, corresponding to different catalyst loading. As
shown in Table 1, the dendrimer immobilized ligands 1a–c
gave excellent yields and enantioselectivities when 5 mol-%
catalysts were used (entries 1–3). When the loading of G3
Figure 4. Reaction rates of the Friedel–Crafts reaction of indole
and nitrostyrene using G1–3 and free ligands.
The G3 ligand 1c (2.5 mol-%) was also tested in the Frie-
ligand 3c was reduced to 2.5 or 1 mol-% (entries 4 and 5), del–Crafts alkylation of some representative substrates, as
the enantioselectivity was not affected but the reaction rate shown in Table 2. Excellent yields and enantioselectivities
decreased significantly. For comparison, the free optimized were achieved in the reactions of aromatic nitroalkenes with
ligand trans-DPBO (2) was also tested at 1–5 mol-% load- both electron-donating and -withdrawing groups at the 4-
ing (entries 6–8). No significant variation in enantio- position (entries 1–3). In the case of the cyclohexyl-contain-
selectivity was observed with increasing dendrimer genera- ing nitroalkene, only a 36% yield was obtained, much lower
tion and lower reaction rates were observed in the immobi- than the yield obtained with the trans-DPBO (2) system
lized catalyst system.
reported previously.[12f] Such a phenomenon indicates that
2124
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 2121–2131

Immobilization of Diphenylamine-Linked Bis(oxazoline) Ligands
Table 3. In situ recycling of the catalyst in the asymmetric Friedel–
Crafts alkyaltion of indole with β-nitrostyrene.[a]
Entry β-Nitrostyrene [mmol]
Indole [mmol] Yield [%][b] ee [%][c]
1
2
3
4
5
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
93
93
93
92
92
92
99[d]
97[e]
98[f]
92[g]
[a] The reactions were conducted in 3 mL of toluene at –20 °C un-
der the catalysis of 5 mol-% catalyst. [b] Isolated yield. [c] Deter-
mined by chiral HPLC on a Daicel Chiralcel OD-H column using
n-hexane/2-propanol (70:30) as eluent. [d] Accumulative yield for
two cycles. [e] Accumulative yield for three cycles. [f] Accumulative
yield for four cycles. [g] Accumulative yield for five cycles.
Figure 5. Reaction rates of the Friedel–Crafts reaction of indole
and nitrostyrene using the G3 ligand with different catalyst loading.
the dendrimer-immobilized ligand is more sensitive towards
the steric effects of the nitroalkene than the free ligand.
When the substituents at the 1- and 5-positions of indole
were Me or MeO, good results were also achieved. The
moderate yield of 17g indicates the lower reactivity of the
N-substituted indole in the nucleophilic reaction. In most
cases, the enantioselectivities decreased by only 3–5% com-
pared with the free ligand system.[12f]
For type II ligand immobilization, we designed the C3-
symmetric G0 dendrimer structure 18 (three-centre cata-
lyst), which can be synthesized from alkynyl-substituted li-
gand 13 and iodide compound 19[24] by copper-free Sono-
gashira coupling, as illustrated in Scheme 7. No desired
product was obtained when the bromide analogue of 19 was
used. The Suzuki–Miyaura coupling of 13 with tris(borate)
or tris(boronic acid) analogues of 19 were also tested, but
no conversion was observed.
Table 2. Application of the G3 ligand in the asymmetric Friedel–
Crafts reaction of indole derivatives with nitroalkenes.[a]
Entry R1
R2
R3
Product Yield [%][b] ee [%][c,d]
1
2
3
4
5
6
7
H
H
H
H
H
MeO
H
H
H
H
H
H
H
Me
Ph
17a
17b
17c
17d
17e
17f
98
99
99
36
93
93
78
93 (R)
92 (R)
93 (R)
87 (R)
86 (R)
94 (R)
92 (R)
4-MeC6H4
4-ClC6H4
Cyclohexyl
PhCH2CH2
Ph
Ph
17g
[a] All the reactions were conducted on a 0.5 mmol scale in 3 mL
of toluene. [b] Isolated yield. [c] Determined by HPLC on Chiracel
OD-H and IA columns using a mixture of hexane and 2-propanol
as eluent (for details see the Supporting Information). [d] The abso-
lute configurations were determined by comparison of the optical
rotations and the retention times on the chiral HPLC columns with
reported results.
To enhance the efficiency with further reduced catalyst
loading, the G3 ligand 1c was tested in the in situ recycling
process.[23] As shown in Table 3, the asymmetric Friedel–
Crafts alkylation of indole 15a with β-nitrostyrene (16a)
was performed with 5 mol-% catalyst. After being stirred
for 24 h at –20 °C, another portion of each of the two sub-
strates was added without isolation of the product. An ex-
cellent accumulative yield and unaffected enantioselectivity
Scheme 7. Synthesis of the designed C3-symmetric three-centre cat-
alyst by a double copper-free Sonogashira coupling reaction.
With the desired ligand 18 in hand, the catalytic activity
were achieved after five cycles. Although the catalytic ac- of its complex with Zn(OTf)2 was investigated in the asym-
tivity of the catalyst was not inhibited by the product, fur- metric Friedel–Crafts alkylation of indole 15a with β-nitro-
ther recycles were not tested owing to the precipitation of styrene (16a) under the optimized conditions we reported
the product from the solution at low temperature.
before.[12f] Because there are three bis(oxazoline) moieties
Eur. J. Org. Chem. 2010, 2121–2131
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2125

H. Liu, D.-M. Du
FULL PAPER
in 18, 1 and 2 mol-% catalyst loadings were tested, and 3 the ee values were not affected significantly. All the results
and 6 mol-% of the free ligand 2 were also tested for com- are similar to those published previously using 5 mol-% of
parison. As shown in Table 4, the immobilized ligand gave the free ligand 2. The slightly lower yields can be attributed
similar catalytic activity and enantioselectivity to the free to the partial precipitation of the complex in toluene at the
ligand.
low temperature. The absolute configurations of the prod-
ucts were determined by comparison of optical rotation val-
ues with the literature.[12d,12f]
Table 4. Catalytic activity of the three-centre catalyst and free li-
gand in the Friedel–Crafts alkylation of indole with nitrostyrene.[a]
To further reduce the catalyst loading, the three-centre
bis(oxazoline) ligand 18 was evaluated in the in situ recycl-
ing process. As shown in Table 6, the asymmetric Friedel–
Crafts alkylation of indole 15a with β-nitrostyrene (16a)
was performed with 2 mol-% catalyst. After being stirred
for 24 h at –20 °C, another portion of each of the two sub-
strates was added without isolation of the product. An ex-
cellent accumulative yield and unaffected enantioselectivity
was achieved after four cycles. Although the catalytic ac-
tivity of the catalyst was not inhibited by the product, fur-
ther recycles were not tested owing to the precipitation of
the product from the solution at low temperature.
Entry
Ligand
Loading [mol-%] Yield [%][b]
ee [%][c]
1
2
3
4
18
18
2
2
1
6
3
96[d]
89[e]
96[d]
88[e]
92
93
95
95
2
[a] The reactions were conducted in 3 mL of toluene at –20 °C. [b]
Isolated yield. [c] Determined by chiral HPLC on a Daicel Chi-
ralcel OD-H column using n-hexane/2-propanol (70:30) as eluent.
[d] The reaction time was 24 h. [e] The reaction time was 48 h.
Table 6. In situ recycling of catalyst in asymmetric Friedel–Crafts
alkylation of indole with β-nitrostyrene.[a]
Run β-Nitrostyrene [mmol]
Indole [mmol] Yield [%][b] ee [%][c]
1
2
3
4
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
96
93
93
92
93
When other indole derivatives and nitroalkenes were
used in our system, good yields and enantioselectivities
were also achieved in most cases, as shown in Table 5. The
yields and enantioselectivities were not sensitive to para and
meta substitutions on the phenyl ring in the aromatic nitro-
alkenes (entries 1–5). Thiophene-containing and aliphatic
nitroalkenes gave lower enantioselectivities than aromatic
ones (entries 6 and 7). The 5-chloroindole with an electron-
withdrawing group (entry 10) and N-methylindole (entry
11) gave low yields because of their low reactivities, whereas
93[d]
92[e]
98[f]
[a] The reactions were conducted in 3 mL of toluene at –20 °C with
2 mol-% catalyst. [b] Isolated yield. [c] Determined by chiral HPLC
on a Daicel Chiralcel OD-H column using n-hexane/2-propanol
(70:30) as eluent. [d] Accumulative yield for two cycles. [e] Accumu-
lative yield for three cycles. [f] Accumulative yield for four cycles.
Table 5. Asymmetric Friedel–Crafts alkyaltion of indole derivatives
with nitroalkenes.[a]
Conclusions
A diphenylamine-linked bis(oxazoline) ligand with trans-
diphenyl substitution on the oxazoline rings was immobi-
lized onto Fréchet-type dendrimers (generations one to
three) and a C3-symmetric core structure by copper-free
Sonogashira coupling. In the asymmetric Friedel–Crafts
alkylation of indole derivatives with nitroalkenes, good
yields and enantioselectivities were achieved in most cases
with values similar to those obtained with the free ligand
system reported previously. The in situ recycling of the cata-
lyst was tested in the asymmetric Friedel–Crafts alkylation
reaction. Excellent accumulative yields and enantio-
selectivities were achieved after four or five cycles. No den-
drimer effect was observed in the kinetic investigation of
the Fréchet-type dendrimer-immobilized ligands. Although
the in situ recycling of the catalyst can be recognized as a
method for reducing the effective catalyst loading of the
reaction, it also provides a potential method for the one-
pot large-scale asymmetric catalytic synthesis of chiral com-
pounds. Further application of the catalyst in a membrane
reactor system is underway in our laboratory.
Entry R1
R2
R3
Product Yield [%][b] ee [%][c,d]
1
H
H
H
H
H
H
H
H
H
H
H
Me
C6H5
17a
17b
17c
17h
17i
89
95
93
85
89
79
86
89
97
41
54
93 (R)
92 (R)
93 (R)
91 (R)
93 (R)
81 (R)
85 (R)
93 (R)
89 (R)
88 (R)
87 (R)
2
H
4-CH3C6H4
4-ClC6H4
4-FC6H4
3-BrC6H4
2-thienyl
PhCH2CH2
C6H5
C6H5
C6H5
C6H5
3
H
4
H
5
H
6
H
17j
7
H
17e
17k
17f
17l
8
9
10
11
Me
MeO
Cl
H
17g
[a] The reactions were conducted in 3 mL of toluene at –20 °C for
48 h. [b] Isolated yield. [c] Determined by chiral HPLC (for details,
see the Supporting Information). [d] The absolute configurations
were determined by comparison of the optical rotations and reten-
tion times on a chiral HPLC column with reported results.
2126
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 2121–2131

Immobilization of Diphenylamine-Linked Bis(oxazoline) Ligands
2-[(2-Carboxyphenyl)amino]-5-iodobenzoic Acid (9b): The desired
product was prepared from 8b following the same procedure as
used for 9a on a 4 mmol scale. The product was obtained by fil-
tration as a yellowish powder (1.530 g, 100% yield); m.p. Ͼ260 °C
(dec). 1H NMR (200 MHz, [D6]DMSO): δ = 13.30 (br., 2 H,
CO2H), 10.92 (s, 1 H, NH), 8.17 (d, J = 2.2 Hz, 1 H, ArH), 7.93
(d, J = 7.6 Hz, 1 H, ArH), 7.71 (dd, J1 = 9.0, J2 = 2.2 Hz, 1 H,
ArH), 7.48 (d, J = 3.6 Hz, 2 H, ArH), 7.30 (d, J = 8.8 Hz, 1 H,
ArH), 6.97–7.05 (m, 1 H, ArH) ppm. 13C NMR (50 MHz, [D6]-
DMSO): δ = 168.1, 167.0, 143.5, 142.5, 141.3, 139.5, 133.2, 131.7,
Experimental Section
Methyl 5-Bromo-2-[(2-methoxycarbonylphenyl)amino]benzoate (8a):
NaHCO3 (0.84 g, 10 mmol) was added to a solution of dimethyl
1,1Ј-diphenylamine-2,2Ј-dicarboxylate (7; 1.425 g, 5 mmol) in
dichloromethane (DCM, 10 mL) and MeOH (5 mL). The mixture
was cooled to 0 °C and pyridinium hydroperbromide (PHPB,
1.60 g, 5 mmol) was added in portions. After the addition, the mix-
ture was warmed to room temperature and stirred overnight. After
being quenched with water, the organic phase was separated and
the water phase extracted with DCM (50 mL). The combined or-
ganic phases were dried with anhydrous Na2SO4. The solvent was
removed under vacuum and the crude product was purified by
recrystallization in toluene. The product 8a was obtained as a
bright greenish solid (1.420 g, 76% yield); m.p. 139–140 °C. 1H
NMR (300 MHz, CDCl3): δ = 11.03 (s, 1 H, NH), 8.10 (s, 1 H,
ArH), 7.99 (d, J = 7.8 Hz, 1 H, ArH), 7.35–7.50 (m, 4 H, ArH),
6.94 (t, J = 7.5 Hz, 1 H, ArH), 3.95 (s, 6 H, CH3) ppm. 13C NMR
(75 MHz, CDCl3): δ = 167.5, 166.5, 143.44, 143.39, 136.0, 134.2,
133.2, 131.8, 120.4, 119.0, 118.2, 117.8, 117.6, 111.1, 52.3,
120.6, 119.3, 119.2, 118.3, 118.2, 80.9 ppm. IR (neat): ν = 2969,
˜
1672, 1586, 1514, 1452, 1316, 1249, 1221, 1168, 912, 835, 743 cm–1.
MS (ESI): m/z = 382 [M – H]+. C14H10INO4 (383.14): calcd. C
43.89, H 2.63, N 3.66; found C 43.94, H 2.77, N 3.70.
5-Bromo-2-[(2-{N-[(1S,2R)-2-hydroxy-1,2-diphenylethyl]carb-
amoyl}phenyl)amino]-N-[(1S,2R)-2-hydroxy-1,2-diphenylethyl]benz-
amide (10a): Compound 9a (2.352 g, 7 mmol) and SOCl2 (10 mL)
were added to a 50 mL round-bottomed flask. The mixture was
heated at reflux for 4 h and excess SOCl2 was removed under vac-
uum. The crude diacyl chloride was dissolved in CH2Cl2 (60 mL)
and added dropwise through a dropping funnel to a mixture of
(1R,2S)-2-amino-1,2-diphenylethanol (2.982 g, 14 mmol) and Et3N
(5.0 mL, 35 mmol) in CH2Cl2 (30 mL) at 0 °C. The mixture was
stirred at room temperature for another 20 h after completion of
the addition. After being quenched with saturated NH4Cl (aq.) and
washed with water, the organic phase was dried with anhydrous
Na2SO4. The bis(β-hydroxyamide) 10a was isolated by silica gel
column chromatography using petroleum ether/ethyl acetate (2:1)
as eluent and obtained as a colourless solid (3.663 g, 72% yield);
m.p. 127–129 °C. [α]2D0 = –54.0 (c = 0.57 g/100 mL, CH2Cl2). 1H
NMR (300 MHz, CDCl3): δ = 9.40 (s, 1 H, NH), 7.73 (d, J =
8.1 Hz, 1 H, ArH), 7.65 (d, J = 2.1 Hz, 1 H, ArH), 7.56 (d, J =
7.8 Hz, 1 H, ArH), 7.48 (d, J = 7.5 Hz, 1 H, ArH), 7.23–7.36 (m,
3 H, ArH), 6.97–7.10 (m, 12 H, ArH), 6.85–6.94 (m, 10 H, ArH),
5.23–5.32 (m, 2 H, CH), 4.97 (dd, J1 = 18.0, J2 = 3.3 Hz, 2 H,
CH), 3.32 (br., 2 H, OH) ppm. 13C NMR (75 MHz, CDCl3): δ =
167.9, 166.2, 142.1, 141.0, 139.8, 139.7, 136.8, 136.7, 134.8, 132.3,
131.8, 128.9, 128.0, 127.8, 127.5, 126.3, 125.8, 123.3, 121.73,
121.68, 121.62, 121.59, 121.5, 119.3, 119.2, 113.9, 75.9, 75.8,
52.1 ppm. IR (neat): ν = 3315, 1698, 1581, 1515, 1431, 1316, 1254,
˜
1211, 1082, 967 cm–1. MS (ESI): m/z
= 364 [M +
H]+.
C16H14BrNO4 (364.19): calcd. C 52.77, H 3.87, N 3.85; found C
52.37, H 3.88, N 3.90.
Methyl 5-Iodo-2-[(2-methoxycarbonylphenyl)amino]benzoate (8b):
NaHCO3 (3.36 g, 40 mmol) was added to a solution of dimethyl
1,1Ј-diphenylamine-2,2Ј-dicarboxylate (7; 5.70 g, 20 mmol) in
DCM (40 mL) and MeOH (20 mL). The mixture was cooled to
0 °C and BnN(CH3)3ICl2 (6.96 g, 20 mmol) was added in portions.
The mixture was warmed to room temperature after the completion
of the addition and stirred overnight. The reaction was quenched
with water and the organic phase was separated. The water phase
was extracted with DCM (100 mL) and the combined organic
phases were dried with anhydrous Na2SO4. The solvent was re-
moved under vacuum to afford the crude product, which was fur-
ther purified by recrystallization in toluene. The product 8b was
obtained as a yellowish solid (4.483 g, 55% yield); m.p. 153–155 °C.
1H NMR (300 MHz, CDCl3): δ = 11.04 (s, 1 H, NH), 8.27 (d, J =
1.8 Hz, 1 H, ArH), 7.99 (d, J = 7.8 Hz, 1 H, ArH), 7.58 (dd, J1 =
8.7, J2 = 2.1 Hz, 1 H, ArH), 7.49 (d, J = 8.1 Hz, 1 H, ArH), 7.29–
7.40 (m, 2 H, ArH), 6.94 (t, J = 7.5 Hz, 1 H, ArH), 3.94 (s, 6 H,
CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 167.5, 166.4, 144.0,
143.2, 141.6, 140.1, 133.2, 131.8, 120.5, 119.2, 118.6, 118.0, 117.7,
59.4 ppm. IR (neat): ν = 3310, 3060, 1636, 1579, 1497, 1313, 1265,
˜
1093, 1060, 739, 701 cm–1. MS (ESI): m/z = 726 [M + H]+.
C42H36BrN3O4 (726.66): calcd. C 69.42, H 4.99, N 5.78; found C
69.12, H 5.03, N 5.81.
80.3, 52.3, 52.1 ppm. IR (neat): ν = 3300, 2944, 1697, 1579, 1512,
˜
1451, 1432, 1313, 1252, 1207, 1079, 750 cm–1. MS (ESI): m/z = 412
[M + H]+. C16H14INO4 (411.19): calcd. C 46.74, H 3.43, N 3.41;
found C 47.50, H 3.54, N 3.50.
2-[(2-{N-[(1S,2R)-2-Hydroxy-1,2-diphenylethyl]carbamoyl}phenyl)-
amino]-N-[(1S,2R)-2-hydroxy-1,2-diphenylethyl]-5-iodobenzamide
(10b): The iodine-substituted bis(β-hydroxyamide) 10b was pre-
pared similarly to 10a on 4 mmol scale. The desired product was
obtained as a colourless solid (2.000 g, 65 % yield); m.p. 137–
139 °C. [α]2D0 = –61.2 (c = 0.94 g/100 mL, CH2Cl2). 1H NMR
(300 MHz, CDCl3): δ = 9.43 (s, 1 H, NH), 7.80 (s, 1 H, ArH), 7.59
(dd, J1 = 11.4, J2 = 8.7 Hz, 2 H, ArH), 7.50 (d, J = 7.2 Hz, 2 H,
ArH), 7.23–7.31 (m, 2 H, ArH), 7.10 (br., 12 H, ArH), 6.82–6.94
(m, 10 H, ArH), 5.25–5.30 (m, 2 H, CH), 4.97 (dd, J1 = 9.9, J2 =
3.0 Hz, 2 H, CH), 3.22 (br., 2 H, OH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 167.7, 166.2, 141.9, 141.7, 140.6, 139.8, 139.7, 137.5,
136.8, 136.7, 132.2, 129.0, 128.0, 127.9, 127.5, 126.3, 125.8, 123.9,
5-Bromo-2-[(2-carboxyphenyl)amino]benzoic Acid (9a): A solution
of NaOH (1.0 g, 25 mmol) in water (10 mL) was added to a solu-
tion of 8a (1.407 g, 3.87 mmol) in MeOH (10 mL). The mixture
was heated at reflux for 3 h and then cooled to room temperature.
After being acidified to pH 1.0 with concentrated HCl (aq.), the
product was obtained by filtration as a greenish powder (1.295 g,
100% yield); m.p. Ͼ260 °C (dec). 1H NMR (200 MHz, [D6]-
DMSO): δ = 13.29 (br., 2 H, CO2H), 11.02 (s, 1 H, NH), 7.98–7.99
(m, 1 H, ArH), 7.96 (d, J = 10.2 Hz, 1 H, ArH), 7.53–7.63 (m, 2
H, ArH), 7.39–7.48 (m, 2 H, ArH), 6.97–7.05 (m, 1 H, ArH) ppm.
13C NMR (50 MHz, [D6]DMSO): δ = 168.1, 167.0, 143.0, 142.6,
135.7, 133.6, 133.2, 131.6, 120.6, 119.2, 118.8, 118.3, 118.0,
122.0, 121.2, 119.7, 83.3, 75.9, 59.4 ppm. IR (neat): ν = 3413, 3062,
˜
1636, 1577, 1497, 1314, 1265, 1091, 1060, 1029, 908, 738, 702 cm–1.
MS (ESI): m/z = 774 [M + H]+. C42H36IN3O4 (773.66): calcd. C
65.20, H 4.69, N 5.43; found C 64.80, H 4.72, N 5.47.
110.1 ppm. IR (neat): ν = 2985, 1676, 1592, 1517, 1456, 1315, 1250,
˜
1218, 1167, 1084, 908 cm–1. MS (ESI): m/z = 334 [M – H]+.
C14H10BrNO4·0.5H2O (345.15): calcd. C 48.72, H 3.21, N 4.06; 4-Bromo-2-[(4S,5S)-4,5-diphenyloxazolin-2-yl]-N-{2-[(4S,5S)-4,5-di-
found C 48.21, H 2.91, N 4.11.
phenyloxazolin-2-yl]phenyl}aniline (11a): MeSO2Cl (0.61 mL,
Eur. J. Org. Chem. 2010, 2121–2131
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2127

H. Liu, D.-M. Du
FULL PAPER
7.8 mmol) and Et3N (2.3 mL, 16 mmol) were added successively to
kyne (427 mg, 90% yield). The TIPS protecting group was removed
a solution of 10a (2.562 g, 3.53 mmol) in CH2Cl2 (20 mL) at 0 °C. by addition of a 1  solution of TBAF in THF (3.0 mL, 3 mmol).
After the addition, the mixture was stirred at room temperature for
10 h. The reaction was quenched with saturated NH4Cl (aq.),
washed with brine and dried with anhydrous Na2SO4. After con-
centration, the residue was dissolved in methanol (10 mL) and
After being stirred at room temperature until full conversion of the
material, the mixture was concentrated, dissolved in DCM
(10 mL), washed with water and dried with anhydrous Na2SO4.
The crude product was purified by silica gel column chromatograph
mixed with NaOH (1.0 g) in water (10 mL). The mixture was using petroleum ether/ethyl acetate (10:1) as eluent and 13 was ob-
heated at reflux for 2 h and then methanol was removed under
vacuum. The residue was extracted with CH2Cl2, washed with brine
and dried with anhydrous Na2SO4. The desired product 11a was
purified by silica gel column chromatography using petroleum
ether/ethyl acetate (10:1) as eluent to give a colourless solid
tained as a colourless solid (316 mg, 92% yield); m.p. 104–106 °C.
[α]2D0 = 76.9 (c = 0.64 g/100 mL, CH2Cl2). 1H NMR (300 MHz,
CDCl3): δ = 11.49 (s, 1 H, NH), 8.14 (s, 1 H, ArH), 7.98 (d, J =
7.8 Hz, 1 H, ArH), 7.62 (d, J = 8.4 Hz, 1 H, ArH), 7.46 (s, 2 H,
ArH), 7.41 (d, J = 8.1 Hz, 1 H, ArH), 7.30 (br., 7 H, ArH), 7.17
(br., 9 H, ArH), 7.04 (br., 5 H, ArH), 5.08–5.12 (m, 2 H, CH), 4.91
(2.041 g, 84% yield); m.p. 108–110 °C. [α]2D0 = 78.0 (c = 0.60 g/
1
100 mL, CH2Cl2). H NMR (300 MHz, CDCl3): δ = 11.32 (s, 1 H, (dd, J1 = 13.2, J2 = 7.5 Hz, 2 H, CH), 3.00 (s, 1 H, CϵCH) ppm.
NH), 8.07 (s, 1 H, ArH), 7.97 (d, J = 7.8 Hz, 1 H, ArH), 7.57 (d,
J = 8.1 Hz, 1 H, ArH), 7.44 (s, 2 H, ArH), 7.38 (d, J = 8.1 Hz, 1 141.77, 140.3, 140.1, 135.2, 134.6, 131.6, 130.8, 128.73, 128.70,
H, ArH), 7.29 (br., 6 H, ArH), 7.16 (br., 10 H, ArH), 6.99–7.04 128.5, 128.3, 128.2, 127.3, 126.4, 126.3, 125.8, 125.7, 121.7, 120.7,
(m, 5 H, ArH), 5.09 (d, J = 7.5 Hz, 2 H, CH), 4.90–4.94 (m, 2 H, 118.1, 116.3, 113.6, 112.0, 88.1, 87.6, 83.5, 78.7, 75.9 ppm. IR
13C NMR (75 MHz, CDCl3): δ = 163.1, 162.5, 144.7, 141.9, 141.82,
CH) ppm. 13C NMR (75 MHz, CDCl3): δ = 163.1, 162.1, 143.0, (neat): ν = 3293, 3032, 2102, 1640, 1579, 1508, 1454, 1319, 1268,
˜
142.6, 142.0, 141.7, 140.4, 140.0, 134.4, 132.9, 131.7, 130.8, 128.8,
128.7, 128.5, 128.3, 128.2, 127.4, 126.4, 126.3, 125.8, 125.7, 120.9,
1050, 973, 758, 697 cm–1. MS (ESI): m/z = 636 [M + H]+.
C44H33N3O2 (635.75): calcd. C 83.13, H 5.23, N 6.61; found C
82.68, H 5.27, N 6.56.
119.3, 116.8, 116.5, 111.0, 87.9, 78.7 ppm. IR (neat): ν = 3031,
˜
1639, 1577, 1508, 1454, 1310, 1257, 1050, 971, 759, 696 cm–1. MS
(ESI): m/z = 690 [M + H]+. C42H32BrN3O2 (690.63): calcd. C 73.04,
H 4.67, N 6.08; found C 73.67, H 4.84, N 6.09.
G1-Derived Iodobenzene 6a: K2CO3 (1.24 g, 9 mmol) and KI
(498 mg, 3 mmol) were added to a solution of 4-iodophenol
(660 mg, 3 mmol) in acetone (25 mL). The mixture was then heated
at reflux for 0.5 h under argon. Then G1-derived bromide 5a
(1.149 g, 3 mmol) and 18-crown-6 (40 mg, 0.15 mmol) were added
and the mixture was heated at reflux for another 8 h. The solvent
was removed under vacuum and the residue was dissolved in water
and extracted with DCM (50 mL). After being dried with anhy-
drous Na2SO4, the solvent was removed under vacuum and the
product 6a was obtained by crystallization in diethyl ether as a
white solid (1.298 g, 83% yield); m.p. 85–87 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.50 (d, J = 8.7 Hz, 2 H, ArH), 7.29–7.39
(m, 10 H, ArH), 6.68 (d, J = 8.7 Hz, 2 H, ArH), 6.62 (s, 2 H, ArH),
6.56 (s, 1 H, ArH), 4.99 (s, 4 H, OCH2), 4.91 (s, 2 H, OCH2) ppm.
13C NMR (75 MHz, CDCl3): δ = 160.1, 158.4, 138.9, 138.2, 136.7,
128.5, 128.0, 127.5, 117.2, 106.2, 101.6, 83.1, 70.0, 69.8 ppm. IR
2-[(4S,5S)-4,5-Diphenyloxazolin-2-yl]-N-{2-[(4S,5S)-4,5-diphenylox-
azolin-2-yl]phenyl}-4-iodoaniline (11b): MeSO2Cl (0.37 mL,
4.7 mmol) and Et3N (1.3 mL, 9.4 mmol) were added successively
to a solution of 10b (1.622 g, 2.1 mmol) in CH2Cl2 (20 mL) at 0 °C.
After the addition, the mixture was stirred at room temperature for
10 h. The reaction was quenched with saturated NH4Cl (aq.),
washed with brine and dried with anhydrous Na2SO4. After con-
centration, the residue was dissolved in methanol (5 mL) and mixed
with NaOH (0.5 g) in water (5 mL). The mixture was heated at
reflux for 2 h and methanol was removed under vacuum. The resi-
due was extracted with CH2Cl2, washed with brine and dried with
anhydrous Na2SO4. The desired product 11b was purified by silica
gel column chromatography using petroleum ether/ethyl acetate
(10:1) as eluent to give a yellowish solid (1.289 g, 83% yield); m.p.
110–112 °C. [α]2D0 = 70.1 (c = 1.2 g/100 mL, CH2Cl2). 1H NMR
(300 MHz, CDCl3): δ = 11.33 (s, 1 H, NH), 8.23 (s, 1 H, ArH),
7.97 (d, J = 7.5 Hz, 1 H, ArH), 7.56–7.61 (m, 2 H, ArH), 7.34–
7.42 (m, 8 H, ArH), 7.16 (br., 9 H, ArH), 7.02 (br., 6 H, ArH),
5.09 (d, J = 7.5 Hz, 2 H, CH), 4.91 (t, J = 7.2 Hz, 2 H, CH) ppm.
13C NMR (75 MHz, CDCl3): δ = 163.1, 162.0, 143.7, 142.3, 141.9,
141.7, 140.3, 140.1, 140.0, 138.8, 138.7, 131.6, 130.8, 128.7, 128.54,
128.52, 128.3, 128.2, 127.4, 126.4, 125.8, 125.7, 121.1, 119.6, 119.3,
(neat): ν = 3032, 2869, 1595, 1484, 1452, 1376, 1283, 1239, 1156,
˜
1059, 1027, 819, 737, 696 cm–1. MS (ESI): m/z = 523 [M + H]+.
C27H23IO3 (522.37): calcd. C 62.08, H 4.44; found C 62.56, H 4.48.
G2-Derived Iodobenzene 6b: K2CO3 (414 mg, 3 mmol) and KI
(166 mg, 3 mmol) were added to a solution of 4-iodophenol
(220 mg, 1 mmol) in acetone (15 mL). The mixture was then heated
at reflux for 0.5 h under argon. Then G2-derived bromide 5b
(807 mg, 1 mmol) and 18-crown-6 (20 mg, 0.075 mmol) were added
and the mixture was heated at reflux for another 12 h. The solvent
was removed under vacuum and the residue was dissolved in water
and extracted with DCM (20 mL). After being dried with anhy-
drous Na2SO4, the solvent was removed under vacuum and the
product 6b was obtained by crystallization in diethyl ether as a
white solid (913 mg, 97% yield); m.p. 105–106 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.49 (d, J = 8.4 Hz, 2 H, Ar), 7.29–7.37
(m, 20 H, ArH), 6.52–6.69 (m, 11 H, ArH), 4.99 (s, 8 H, OCH2),
4.93 (s, 4 H, OCH2), 4.90 (s, 2 H, OCH2) ppm. 13C NMR (75 MHz,
CDCl3): δ = 160.1, 160.0, 158.4, 139.1, 138.9, 138.2, 136.7, 128.5,
127.9, 127.5, 117.3, 117.2, 106.4, 106.3, 101.6, 83.1, 70.0, 69.93,
117.1, 116.7, 87.9, 80.1, 78.6 ppm. IR (neat): ν = 3031, 1638, 1575,
˜
1507, 1454, 1310, 1264, 1050, 970, 814, 737, 696 cm–1. MS (ESI):
m/z = 738 [M + H]+. C42H32IN3O2 (737.63): calcd. C 68.39, H 4.37,
N 5.70; found C 69.04, H 4.63, N 5.70.
2-[(4S,5S)-4,5-Diphenyloxazolin-2-yl]-N-{2-[(4S,5S)-4,5-diphenylox-
azolin-2-yl]phenyl}-4-ethynylaniline (13): Compound 11a (414 mg,
0.60 mmol), [Pd(PPh3)2Cl2] (21 mg, 0.03 mmol), (triisopropylsilyl)
acetylene (12; 0.18 mL, 0.8 mmol) and DMF (1 mL) were added to
a Schlenk tube under argon. The mixture was heated to 80 °C and
the reaction was initiated by the addition of piperidine (90 µL,
0.92 mmol). After being stirred at 80 °C for 12 h, the mixture was
cooled and the reaction was quenched by the addition of water.
The mixture was extracted with DCM (10 mL). The organic phase
was dried with anhydrous Na2SO4, concentrated under vacuum
and purified by silica gel flash chromatography using petroleum
ether/ethyl acetate (15:1) as eluent to afford the TIPS-protected al-
69.85 ppm. IR (neat): ν = 3032, 1595, 1484, 1452, 1375, 1294, 1239,
˜
1153, 1055, 829, 735, 698 cm–1. MS (ESI): m/z = 947 [M + H]+.
C55H47IO7 (946.86): calcd. C 69.77, H 5.00; found C 69.52, H 4.96.
G3-Derived Iodobenzene 6c: K2CO3 (414 mg, 3 mmol) and KI
(166 mg, 3 mmol) were added to a solution of 4-iodophenol
2128
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 2121–2131

Immobilization of Diphenylamine-Linked Bis(oxazoline) Ligands
(220 mg, 1 mmol) in acetone (15 mL). The mixture was then heated
at reflux for 0.5 h under argon. Then G3-derived bromide 5c
(1.655 g, 1 mmol) and 18-crown-6 (20 mg, 0.075 mmol) were added
and the mixture was heated at reflux for another 24 h. The solvent
was removed under vacuum and the residue was dissolved in water
and extracted with DCM (30 mL). After being dried with anhy-
drous Na2SO4, the solvent was removed under vacuum and the
product 6c was obtained by crystallization in diethyl ether as a
white solid (1.673 g, 93% yield); m.p. 73–75 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.46 (d, J = 8.1 Hz, 2 H, ArH), 7.26–7.35
(m, 40 H, ArH), 6.64 (s, 15 H, ArH), 6.54 (s, 8 H, ArH), 4.96 (s,
(neat): ν = 3030, 2923, 1639, 1595, 1513, 1453, 1374, 1295, 1155,
˜
1050, 973, 830, 738, 696 cm–1. HRMS (ESI): calcd. for C99H80N3O9
[M + H]+ 1454.58946; found 1454.58207.
G3-Dendrimer Ligand 1c: Alkyne 13 (127 mg, 0.2 mmol), G3-de-
rived iodobenzene 6c (359 mg, 0.2 mmol), [Pd(PPh3)2Cl2] (7 mg,
0.01 mmol) and DMF (1 mL) were added to a Schlenk tube under
argon. The mixture was heated to 80 °C and the reaction was initi-
ated by the addition of piperidine (30 µL, 0.31 mmol). The mixture
was stirred at 80 °C for 24 h and the reaction was quenched by
the addition of water at room temperature. The mixture was then
extracted with DCM (20 mL). The organic phase was dried with
anhydrous Na2SO4, concentrated under vacuum and purified by
silica gel column chromatography using DCM as eluent. The de-
sired product 1c was obtained as a light-orange foam (378 mg, 82%
yield); m.p. 85–87 °C. [α]2D0 = –1.2 (c = 0.90 g/100 mL, CH2Cl2). 1H
NMR (300 MHz, CDCl3): δ = 11.49 (s, 1 H, NH), 8.16 (s, 1 H,
ArH), 7.98 (d, J = 7.5 Hz, 1 H, ArH), 7.30–7.64 (m, 54 H, ArH),
7.15–7.19 (m, 9 H, ArH), 7.04 (d, J = 4.2 Hz, 5 H, ArH), 6.87 (d,
J = 8.4 Hz, 1 H, ArH), 6.66 (s, 14 H, ArH), 6.55 (s, 7 H, ArH),
4.88–5.11 (m, 34 H, CH, OCH2) ppm. 13C NMR (75 MHz,
CDCl3): δ = 163.1, 162.6, 160.1, 160.0, 158.4, 143.8, 142.1, 141.94,
141.86, 140.3, 140.1, 139.2, 136.7, 134.5, 133.8, 132.8, 131.6, 130.8,
128.70, 128.68, 128.5, 128.24, 128.19, 127.9, 127.5, 127.3, 126.4,
126.3, 125.8, 125.7, 121.3, 120.2, 117.5, 116.7, 116.0, 114.8, 114.1,
113.9, 106.3, 101.6, 88.3, 88.01, 87.96, 87.6, 78.7, 70.0, 69.9,
69.8 ppm. IR (neat): ν˜ = 2922, 1639, 1595, 1513, 1452, 1374, 1296,
1153, 1051, 830, 735, 696 cm–1. HRMS (ESI): calcd. for
16 H, OCH2), 4.90 (s, 12 H, OCH2), 4.85 (s, 2 H, OCH2) ppm. 13
C
NMR (75 MHz, CDCl3): δ = 160.1, 160.0, 158.4, 139.15, 139.12,
139.0, 138.1, 136.7, 128.5, 127.9, 127.5, 117.3, 117.2, 106.4, 106.3,
101.6, 101.5, 83.1, 70.1, 70.0, 69.9, 69.8 ppm. IR (neat): ν = 3032,
˜
1594, 1452, 1374, 1295, 1153, 1054, 834, 737, 695 cm–1. MS (ESI):
m/z = 1796 [M + H]+. C111H95IO15 (1795.84): calcd. C 74.24, H
5.33; found C 74.48, H 5.31.
G1-Dendrimer Ligand 1a: Alkyne 13 (127 mg, 0.2 mmol), G1-de-
rived iodobenzene 6a (104 mg, 0.2 mmol), [Pd(PPh3)2Cl2] (7 mg,
0.01 mmol) and DMF (1 mL) were added to a Schlenk tube under
argon. The mixture was heated to 80 °C and the reaction was initi-
ated by the addition of piperidine (30 µL, 0.31 mmol). The mixture
was stirred at 80 °C for 24 h and the reaction was quenched by
the addition of water at room temperature. The mixture was then
extracted with DCM (20 mL). The organic phase was dried with
anhydrous Na2SO4, concentrated under vacuum and purified by
silica gel column chromatography using DCM as eluent. The de-
sired product 1a was obtained as a light-pink foam (132 mg, 64%
yield); m.p. 97–99 °C. [α]2D0 = –9.1 (c = 0.47 g/100 mL, CH2Cl2). 1H
NMR (300 MHz, CDCl3): δ = 11.47 (s, 1 H, NH), 8.16 (s, 1 H,
ArH), 7.97 (d, J = 6.9 Hz, 1 H, ArH),6.88–7.64 (m, 39 H, ArH),
6.66 (s 2 H, ArH), 6.57 (s, 1 H, ArH), 4.89–5.10 (m, 10 H, CH,
OCH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 163.2, 162.7, 160.1,
158.4, 143.8, 142.1, 141.9, 140.3, 140.1, 139.1, 136.7, 134.5, 133.9,
132.8, 131.6, 130.8, 128.7, 128.5, 128.3, 128.2, 128.0, 127.5, 127.3,
126.4, 125.8, 125.7, 121.3, 120.3, 117.6, 116.7, 116.0, 114.9, 114.1,
113.9, 106.3, 101.6, 88.2, 88.0, 87.6, 78.6, 70.1, 69.9 ppm. IR (neat):
C
155H128N3O17 [M + H]+ 2302.92437; found 2302.92691.
C3-Symmetric Dendrimer-Immobilized Ligand (18): Alkyne 13
(222 mg, 0.35 mmol), iodide compound 19 (68 mg, 0.1 mmol),
[Pd(PPh3)2Cl2] (11 mg, 0.015 mmol, 5 mol-% with respect to iodine
atom) and DMF (1 mL) were added to a Schlenk tube under argon.
The mixture was heated to 80 °C and the reaction was initiated by
the addition of piperidine (55 µL, 0.57 mmol). The mixture was
stirred at 80 °C for 48 h and the reaction was quenched by the
addition of water at room temperature. The mixture was then ex-
tracted with CH2Cl2 (20 mL). The organic phase was dried with
anhydrous Na2SO4, concentrated under vacuum and purified by
silica gel column chromatography using CH2Cl2 as eluent. The de-
sired product 18 was obtained as a light-pink solid (121 mg, 55%
yield); m.p. 165–167 °C. [α]2D0 = –86.5 (c = 0.52 g/100 mL, CH2Cl2).
1H NMR (300 MHz, CDCl3): δ = 11.53 (s, 3 H, NH), 8.21 (s, 3 H,
ArH), 7.99 (d, J = 7.5 Hz, 3 H, ArH), 7.79 (s, 3 H, ArH), 7.42–
7.66 (m, 25 H, ArH), 7.06–7.30 (m, 62 H, ArH), 5.12 (t, J = 6.9 Hz,
6 H, CH), 4.93 (t, J = 8.7 Hz, 1 H, CH) ppm. 13C NMR (75 MHz,
CDCl3): δ = 78.7, 87.6, 88.0, 88.2, 90.3, 113.3, 113.9, 116.6, 117.9,
120.6, 121.5, 121.6, 123.0, 124.97, 125.01, 125.7, 125.9, 126.4,
127.2, 127.3, 128.26, 128.29, 128.32, 128.5, 128.7, 130.9, 131.6,
131.9, 134.2, 134.7, 140.1, 140.2, 140.3, 141.7, 141.87, 141.93,
ν = 3033, 2921, 1638, 1597, 1513, 1454, 1305, 1256, 1156, 1051,
˜
971, 829, 747, 696 cm–1. HRMS (ESI): calcd. for C71H56N3O5 [M
+ H]+ 1030.42200; found 1030.41944.
G2-Dendrimer Ligand 1b: Alkyne 13 (127 mg, 0.2 mmol), G2-de-
rived iodobenzene 6b (189 mg, 0.2 mmol), [Pd(PPh3)2Cl2] (7 mg,
0.01 mmol) and DMF (1 mL) were added to a Schlenk tube under
argon. The mixture was heated to 80 °C and the reaction was initi-
ated by the addition of piperidine (30 µL, 0.31 mmol). The mixture
was stirred at 80 °C for 24 h and the reaction was quenched by
the addition of water at room temperature. The mixture was then
extracted with DCM (20 mL). The organic phase was dried with
anhydrous Na2SO4, concentrated under vacuum and purified by
silica gel column chromatography using DCM as eluent. The de-
sired product 1b was obtained as a light-pink foam (155 mg, 53%
144.3, 162.6, 163.1 ppm. IR (neat): ν = 2923, 1637, 1580, 1515,
˜
1456, 1321, 1258, 1050, 977, 828, 752, 698 cm–1. HRMS (ESI):
calcd. for C156H112N9O6 [M + H]+ 2206.87301; found 2206.87217.
1
yield); m.p. 94–96 °C. [α]2D0 = 4.0 (c = 0.80 g/100 mL, CH2Cl2). H
Supporting Information (see also the footnote on the first page of
this article): Experimental protocols for the synthesis of all Friedel–
NMR (300 MHz, CDCl3): δ = 11.51 (s, 1 H, NH), 8.17 (s, 1 H,
ArH), 7.98 (d, J = 7.8 Hz, 1 H, ArH), 7.28–7.65 (m, 34 H, ArH),
7.17 (s, 9 H, ArH), 7.05 (s, 4 H, ArH), 6.88 (d, J = 7.8 Hz, 2 H,
ArH), 6.65 (s, 6 H, ArH), 6.56 (s, 2 H, ArH), 4.89–5.10 (m, 18 H,
CH, OCH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 163.1, 162.6,
160.1, 160.0, 158.4, 143.8, 142.1, 141.9, 141.8, 140.3, 140.1, 139.14,
139.07, 136.7, 134.5, 133.8, 132.8, 131.5, 130.7, 128.68, 128.66,
1
Crafts adducts, H and 13C NMR spectra of the new compounds
and HPLC spectra.
Acknowledgments
128.5, 128.22, 128.17, 127.9, 127.5, 127.3, 126.35, 126.32, 125.8, We thank the National Natural Science Foundation of China
125.7, 121.3, 120.2, 117.5, 116.7, 116.0, 114.8, 114.0, 113.8, 106.3, (Grant numbers 20772006 and 20572003), the Development Pro-
106.2, 101.5, 88.2, 88.0, 87.9, 87.6, 78.7, 70.0, 69.9, 69.8 ppm. IR gram for Distinguished Young and Middle-Aged Teachers of Beij-
Eur. J. Org. Chem. 2010, 2121–2131
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2129

H. Liu, D.-M. Du
FULL PAPER
2007, 18, 108; n) L. Gu, Y. Wu, Y. Zhang, G. Zhao, J. Mol.
Catal. A 2007, 263, 186.
ing Institute of Technology and the Program for New Century Ex-
cellent Talents in University (NCET-07-0011).
[8]
For selected reviews, see: a) G. E. Oosterom, J. N. H. Reek,
P. C. J. Kamer, P. W. N. M. van Leeuwen, Angew. Chem. 2001,
113, 1878; Angew. Chem. Int. Ed. 2001, 40, 1828; b) D. Astruc,
F. Chardac, Chem. Rev. 2001, 101, 2991; c) R. van Heerbeek,
P. C. J. Kamer, P. W. N. M. van Leeuwen, J. N. H. Reek, Chem.
Rev. 2002, 102, 3717; d) L. J. Twyman, A. S. H. King, I. K.
Martin, Chem. Soc. Rev. 2002, 31, 69; e) J. K. Kassube, L. H.
Gade, Top. Organomet. Chem. 2006, 20, 61.
[1]
[2]
a) E. N. Jacobsen, A. Pfaltz, H. Yamamoto (Eds.), Comprehen-
sive Asymmetric Catalysis I-III, Springer, Berlin, 2000; b) H. U.
Blaser, E. Schmidt (Eds.) Asymmetric Catalysis on Industrial
Scale: Challenges, Approaches, and Solutions, Wiley-VCH,
Weinheim, 2004.
For selected reviews, see: a) Q.-H. Fan, Y.-M. Li, A. S. C.
Chan, Chem. Rev. 2002, 102, 3385; b) D. Rechavi, M. Lemaire,
Chem. Rev. 2002, 102, 3467; c) M. Heitbaum, F. Glorius, I.
Escher, Angew. Chem. 2006, 118, 4850; Angew. Chem. Int. Ed.
2006, 45, 4732; d) A. F. Trindade, P. M. P. Gois, C. A. M.
Afonso, Chem. Rev. 2009, 109, 418; e) D. E. de Vos, I. F. Vanke-
lecom, P. A. Jacobs (Eds.), Chiral Catalyst Immobilization and
Recycling, Wiley-VCH, Weinheim, 2000; f) A. Kirschning
(Ed.), Immobilized Catalysts: Solid Phases, Immobilization and
Applications, in: Topics in Current Chemistry, Springer, Berlin,
2004, 242, p. 1; g) J. Cole-Hamilton, R. P. Tooze (Eds.), Cata-
lyst Separation, Recovery and Recycling: Chemistry and Process
Design, Springer, Berlin, 2006; h) D. R. Buchmeiser (Ed.), Poly-
meric Materials in Organic Synthesis and Catalysis, Wiley-
VCH, Weinheim, 2006; i) K. Ding, Y. Uozumi (Eds.), Hand-
book of Asymmetric Heterogeneous Catalysis, Wiley-VCH,
Weinheim, 2008.
[9]
For a review, see: B. Helms, J. M. J. Fréchet, Adv. Synth. Catal.
2006, 348, 1125.
[10]
For recent examples of positive effects in asymmetric catalysis,
see: a) Q.-S. Hu, V. Pugh, M. Sabat, L. Pu, J. Org. Chem. 1999,
64, 7528; b) R. Breinbauer, E. N. Jacobsen, Angew. Chem.
2000, 112, 3750; Angew. Chem. Int. Ed. 2000, 39, 3604; c) Q.-
H. Fan, Y.-M. Chen, X.-M. Chen, D.-Z. Jiang, F. Xi, A. S. C.
Chan, Chem. Commun. 2000, 789; d) Y. Ribourdouille, G. D.
Engel, M. Richard-Plouet, L. H. Gade, Chem. Commun. 2003,
1228; e) Y. Wu, Y. Zhang, M. Yu, G. Zhao, Org. Lett. 2006, 8,
4417; f) Z.-J. Wang, G.-J. Deng, Y. Li, Y.-M. He, W.-J. Tang,
Q.-H. Fan, Org. Lett. 2007, 9, 1243; g) J. K. Kassube, H. Wade-
pohl, L. H. Gade, Adv. Synth. Catal. 2009, 351, 607.
a) H. A. McManus, P. J. Guiry, J. Org. Chem. 2002, 67, 8566;
b) H. A. McManus, P. G. Cozzi, P. J. Guiry, Adv. Synth. Catal.
2006, 348, 551; c) S. C. McKeon, H. Müller-Bunz, P. J. Guiry,
Eur. J. Org. Chem. 2009, 4833; d) V. Coeffard, M. Aylward,
P. J. Guiry, Angew. Chem. 2009, 121, 9316; Angew. Chem. Int.
Ed. 2009, 48, 9152.
a) S.-F. Lu, D.-M. Du, S.-W. Zhang, J. Xu, Tetrahedron: Asym-
metry 2004, 15, 3433; b) D.-M. Du, S.-F. Lu, T. Fang, J. Xu, J.
Org. Chem. 2005, 70, 3712; c) S.-F. Lu, D.-M. Du, J. Xu, S.-W.
Zhang, J. Am. Chem. Soc. 2006, 128, 7418; d) S.-F. Lu, D.-M.
Du, J. Xu, Org. Lett. 2006, 8, 2115; e) H. Liu, J. Xu, D.-M.
Du, Org. Lett. 2007, 9, 4725; f) H. Liu, S.-F. Lu, J. Xu, D.-M.
Du, Chem. Asian J. 2008, 3, 1111; g) H. Liu, W. Li, D.-M. Du,
Sci. China, Ser. B 2009, 52, 1321.
[11]
[12]
[3]
For selected reviews, see: a) J. M. Fraile, J. I. Garcia, J. A.
Mayoral, Chem. Rev. 2009, 109, 360; b) M. Tada, Y. Iwasawa,
Chem. Commun. 2006, 2833; c) C. Li, Catal. Rev. 2004, 46, 419;
d) C. E. Song, S.-G. Li, Chem. Rev. 2002, 102, 3495.
[4]
[5]
For reviews, see: Z. Wang, G. Chen, K. Ding, Chem. Rev. 2009,
109, 322.
For recent examples, see: a) X. Wang, K. Ding, J. Am. Chem.
Soc. 2004, 126, 10524; b) L. Shi, X. Wang, C. A. Sandoval, M.
Li, Q. Qi, Z. Li, K. Ding, Angew. Chem. 2006, 118, 4214; An-
gew. Chem. Int. Ed. 2006, 45, 4108; c) J. H. Yoon, Y. J. Park,
J. H. Lee, J. Yoo, C.-H. Jun, Org. Lett. 2005, 7, 2889; d) D.-W.
Kim, S.-G. Lim, C.-H. Jun, Org. Lett. 2006, 8, 2937.
[13]
[14]
H. Nishiyama, A. Furuta, Chem. Commun. 2007, 760.
C. J. Hawker, J. M. J. Fréchet, J. Am. Chem. Soc. 1990, 112,
7638.
[6]
For a review, see: a) C. Müller, M. G. Nijkamp, D. Vogt, Eur. J.
Inorg. Chem. 2005, 4011; for recent examples using membrane
reactors in catalysis, see: b) N. J. Hovestad, E. B. Eggeling, H. J.
Heidbuchel, J. T. B. H. Jastrzebski, U. Kragl, W. Keim, D.
Vogt, G. van Koten, Angew. Chem. 1999, 111, 1763; Angew.
Chem. Int. Ed. 1999, 38, 1655; c) E. B. Eggeling, N. J. Hoves-
tad, J. T. B. H. Jastrzebski, D. Vogt, G. van Koten, J. Org.
Chem. 2000, 65, 8857; d) R. Sablong, U. Schlotterbeck, D.
Vogt, S. Mecking, Adv. Synth. Catal. 2003, 345, 333; e) H. P.
Dijkstra, N. Ronde, G. P. M. van Klink, D. Vogt, G. van Koten,
Adv. Synth. Catal. 2003, 345, 364; f) M. Janssen, C. Müller, D.
Vogt, Adv. Synth. Catal. 2009, 351, 313; g) M. Gaab, S.
Bellemin-Laponnaz, L. H. Gade, Chem. Eur. J. 2009, 15, 5450.
For a review, see: a) Y.-D. Lu, Y.-H. Wang, Z.-L. Jin, Chin. J.
Org. Chem. 2006, 26, 181; for recent examples, see: b) Y. Wu,
C. Lu, W. Shan, X. Li, Tetrahedron: Asymmetry 2009, 20, 584;
c) Y. Uozumi, Y. Matsuura, T. Arakawa, Y. M. A. Yamada,
Angew. Chem. 2009, 121, 2746; Angew. Chem. Int. Ed. 2009,
48, 2708; d) R. Zimmer, V. Dekaris, M. Knauer, L. Schefzig,
H.-U. Reissig, Synth. Commun. 2009, 39, 1012; e) J. Liu, D.
Zhou, X. Jia, L. Huang, X. Li, A. S. C. Chan, Tetrahedron:
Asymmetry 2008, 19, 1824; f) Y. Uozumi, T. Suzuka, Synthesis
2008, 1960; g) J. Liu, Y. Zhou, Y. Wu, X. Li, A. S. C. Chan,
Tetrahedron: Asymmetry 2008, 19, 832; h) S. H. Chan, K. H.
Lam, Y.-M. Li, L. Xu, W. Tang, F. L. Lam, W. H. Lo, W. Y.
Yu, Q. Fan, A. S. C. Chan, Tetrahedron: Asymmetry 2007, 18,
2625; i) L.-T. Chai, Q.-R. Wang, F.-G. Tao, J. Mol. Catal. A
2007, 276, 137; j) Y. Uozumi, Pure Appl. Chem. 2007, 79, 1481;
k) M. Bandini, M. Benaglia, R. Sinisi, S. Tommasi, A. Umani-
Ronchi, Org. Lett. 2007, 9, 2151; l) L. T. Chai, W.-W. Wang,
Q.-R. Wang, F.-G. Tao, J. Mol. Catal. A 2007, 270, 83; m) X.
Wang, L. Yin, T. Yang, Y. Wang, Tetrahedron: Asymmetry
[15]
For recent applications of Fréchet-type dendrimers in catalysis,
see: a) Y. Li, Y.-M. He, Z.-W. Li, F. Zhang, Q.-H. Fan, Org.
Biomol. Chem. 2009, 7, 1890; b) W. Zhang, L. Li, Y. Du, X.
Wang, P. Yang, Catal. Lett. 2009, 127, 429; c) A. V. Gaikwad,
V. Boffa, J. E. Ten Elshof, G. Rothenberg, Angew. Chem. 2008,
120, 5487; Angew. Chem. Int. Ed. 2008, 47, 5407; d) T. Fujih-
ara, Y. Obora, M. Tokunaga, Y. Tsuji, Dalton Trans. 2007,
1567; e) U. Luening, T. Marquardt, Synthesis 2005, 1383; f) B.
Helms, C. O. Liang, C. J. Hawker, J. M. J. Fréchet, Macromole-
cules 2005, 38, 5411; g) X. Zhang, H. Xu, Z. Dong, Y. Wang,
J. Liu, J. Shen, J. Am. Chem. Soc. 2004, 126, 10556; h) M. D.
Drake, F. V. Bright, M. R. Detty, J. Am. Chem. Soc. 2003, 125,
12558; i) B.-Y. Yang, X.-M. Chen, G.-J. Deng, Y.-L. Zhang,
Q.-H. Fan, Tetrahedron Lett. 2003, 44, 3535; j) G.-J. Deng, Q.-
H. Fan, X.-M. Chen, Chin. J. Chem. 2002, 20, 1139; k) P. B.
Rheiner, D. Seebach, Chem. Eur. J. 1999, 5, 3221.
[7]
[16]
D. Xie, M. Jiang, G. Zhang, D. Chen, Chem. Eur. J. 2007, 13,
3346.
[17]
[18]
[19]
D. V. Kosynkin, J. M. Tour, Org. Lett. 2001, 3, 991.
C. Yi, R. Hua, Catal. Commun. 2006, 7, 377.
For a discussion of the mechanism, see: N. T. S. Phan, M.
van der Sluys, C. W. Jones, Adv. Synth. Catal. 2006, 348, 609.
I. M. Mahmud, N. Zhou, L. Wang, Y. Zhao, Tetrahedron 2008,
64, 11420.
For an example of Ru-catalyzed click [3+2] reactions, see: L.
Zhang, X. Chen, P. Xue, H. H. Y. Sun, I. D. Williams, K. B.
Sharpless, V. V. Fokin, G. Jia, J. Am. Chem. Soc. 2005, 127,
15998.
For a recent review, see: a) M. Bandini, A. Eichholzer, Angew.
Chem. 2009, 121, 9786; Angew. Chem. Int. Ed. 2009, 48, 9608;
[20]
[21]
[22]
2130
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 2121–2131

Immobilization of Diphenylamine-Linked Bis(oxazoline) Ligands
for recent examples of asymmetric Friedel–Crafts reactions
using nitroalkenes as acceptor, see: b) R. P. Herrera, V. Sgarz-
ani, L. Bernardi, A. Ricci, Angew. Chem. 2005, 117, 6734; An-
gew. Chem. Int. Ed. 2005, 44, 6576; c) W. Zhuang, R. G. Hazell,
K. A. Jørgensen, Org. Biomol. Chem. 2005, 3, 2566; d) Y.-X.
Jia, S.-F. Zhu, Y. Ying, Q.-L. Zhou, J. Org. Chem. 2006, 71,
75; e) M. Bandini, A. Garelli, M. Rovinetti, M. Tommasi, A.
Umani-Ronchi, Chirality 2005, 17, 522; f) E. M. Fleming, T.
McCabe, S. J. Connon, Tetrahedron Lett. 2006, 47, 7037; g)
P. K. Singh, A. Bisai, V. K. Singh, Tetrahedron Lett. 2007, 48,
1127; h) Y. Sui, L. Liu, J.-L. Zhao, D. Wang, Y.-J. Chen, Tetra-
hedron 2007, 63, 5173; i) J. Itoh, K. Fuchibe, T. Akiyama, An-
gew. Chem. 2008, 120, 4080; Angew. Chem. Int. Ed. 2008, 47,
4016; j) T. Arai, N. Yokoyama, A. Yanagisawa, Chem. Eur. J.
2008, 14, 2052; k) T. Arai, N. Yokoyama, Angew. Chem. 2008,
120, 5067; Angew. Chem. Int. Ed. 2008, 47, 4989; l) B. M. Trost,
C. Müller, J. Am. Chem. Soc. 2008, 130, 2438; m) S.-Z. Lin, T.-
P. You, Tetrahedron 2009, 65, 1010; n) Y.-F. Sheng, G.-Q. Li,
Q. Kang, A.-J. Zhang, S.-L. You, Chem. Eur. J. 2009, 15, 3351;
o) N. Yokoyama, T. Arai, Chem. Commun. 2009, 3285.
For examples, see: a) N. J. Gilmore, S. Jones, M. P. Muldowney,
Org. Lett. 2004, 6, 2805; b) D.-M. Du, T. Fang, J. Xu, S.-W.
Zhang, Org. Lett. 2006, 8, 1327.
[23]
[24] M. J. Plater, M. McKay, T. Jackson, J. Chem. Soc. Perkin
Trans. 1 2000, 2695.
Received: December 9, 2009
Published Online: March 4, 2010
Eur. J. Org. Chem. 2010, 2121–2131
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2131