Polyethyleneimine-Supported Triphenylphosphine and Its Use as a Highly Loaded Bifunctional Polymeric Reagent in Chromatography-Free One-Pot Wittig Reactions

Article abstract of DOI:10.1055/s-0034-1380810

A polyethyleneimine-supported triphenylphosphine reagent has been synthesized and used as a highly loaded bifunctional homogeneous reagent in a range of one-pot Wittig reactions that afforded high yields of the desired products after simple purification procedures. The approach also served efficiently in tandem reaction sequences involving a one-pot Wittig reaction followed by conjugate reduction of the newly formed alkene product in situ. In these transformations, the phosphine oxide groups generated in the Wittig reaction served as the catalyst for activating trichlorosilane in the subsequent reduction reaction.

Full text of DOI:10.1055/s-0034-1380810

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
© Georg Thieme Verlag Stuttgart · New York
2015, 26, 1737–1743
letter
1737
X. Xia, P. H. Toy
Letter
Synlett
Polyethyleneimine-Supported Triphenylphosphine and Its Use as
a Highly Loaded Bifunctional Polymeric Reagent in Chromatogra-
phy-Free One-Pot Wittig Reactions
Ph2P
Xuanshu Xia
Patrick H. Toy*
PPh2
PPh2
N
Department of Chemistry, The University of Hong Kong,
Pokfulam Road, Hong Kong, P. R. of China
phtoy@hku.hk
N
N
O
+
O
N
N
N
R1
H
N
N
N
N
R1
R3
R2
O
N
n
X
N
N
41 examples
85–100% yield
R3
R2
Ph2P
PPh2
PEI-TPP
Received: 25.03.2015
Accepted after revision: 20.04.2015
Published online: 18.06.2015
ture. Therefore, the development of an easily synthesized
polymer-supported phosphine reagent that is highly loaded
and very reactive and that can be easily removed from the
desired product after the reaction could be of significant
general interest.
DOI: 10.1055/s-0034-1380810; Art ID: st-2015-w0209-l
Abstract A polyethyleneimine-supported triphenylphosphine reagent
has been synthesized and used as a highly loaded bifunctional homoge-
neous reagent in a range of one-pot Wittig reactions that afforded high
yields of the desired products after simple purification procedures. The
approach also served efficiently in tandem reaction sequences involv-
ing a one-pot Wittig reaction followed by conjugate reduction of the
newly formed alkene product in situ. In these transformations, the
phosphine oxide groups generated in the Wittig reaction served as the
catalyst for activating trichlorosilane in the subsequent reduction reac-
tion.
We have been developing new organic polymers for use
as reagents and catalyst supports,8,9 and we recently report-
ed the synthesis and application of several rasta resin triph-
enylphosphines in various Wittig reactions from which the
desired products did not require chromatographic purifica-
tion. Our initial polymer-supported reagent 1 was mono-
functional, and only bore phosphine groups (Figure 1).10 We
were interested in performing one-pot Wittig reactions11 in
which the required phosphorane reagent was formed in
situ by deprotonation of a phosphonium salt; therefore, a
separate amine base had to be added to the reactions when
1 was used. Thus, we later developed bifunctional rasta res-
ins 2 and 3, which were functionalized with tertiary amine
groups in addition to the phosphine groups.12,13 Although
these polymer-supported reagents were easily synthesized
and more reactive than traditional heterogeneous polymer-
supported phosphines, they suffered from low loading lev-
els (ca. 1 mmol/g amine and phosphine) because of the
polystyrene platform on which they were based.
To identify a more useful and practical bifunctional
polymer-supported reagent for Wittig reactions, we sought
to prepare a polymer based on commercially available poly-
ethylene imine (PEI, 4; Figure 2)14 that is highly loaded with
both amine and phosphine groups. In fact, because of its
high density of amine groups, 4 has previously been used as
a platform in various forms for polymer-supported synthe-
sis and reagents.15 For example, both Ultraresin (5)16 and
ULTRAMINE (6)17 have been described in the literature, and,
Key words conjugate reduction, polyethyleneimine, polymer sup-
ported reagents, triphenylphosphine, Wittig reactions
The classic Wittig reaction is one of the most versatile
and widely used methods for converting the carbon–oxy-
gen double bond of an aldehyde or ketone into a carbon–
carbon double bond.1,2 While they are generally very effi-
cient and can be highly stereoselective, Wittig reactions
suffer from the drawback that an equivalent of a phosphine
oxide byproduct is formed in conjunction with the desired
product. Thus, even in high-yielding reactions, the desired
product generally requires extensive purification, and
therefore, Wittig reactions are not considered to be envi-
ronmentally sound.3 To address this issue, much research
has been directed towards developing solutions to the
problem of byproduct separation, including the use of poly-
mer-supported phosphines4 that allow the waste to be re-
moved simply by filtration.5–7 However, the polymer-sup-
ported phosphine reagents reported to date have limita-
tions such as low phosphorous loading levels (typically
1 mmol/g), or low reactivity due to their heterogeneous na-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1737–1743

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X. Xia, P. H. Toy
Letter
Synlett
The synthesis of 8 started with 4-bromobenzaldehyde
living radical polymerization
initiation groups
(9), which was protected with ethylene glycol to form 10
(Scheme 1). This, in turn, was treated with n-BuLi followed
by ClP(Ph)2 to form triarylphosphine 11. Acid-catalyzed hy-
drolytic deprotection of the aldehyde group of 11 generated
12, which was reacted with 4 (MW = ca. 25,000) together
with acetaldehyde and NaBH3CN to afford 8. At this stage, IR
spectroscopy was used to verify that the original primary
and secondary amine groups of 4 (3277 cm–1) were convert-
ed into tertiary amine groups in 8.19 Additionally, 8 exhibited
only a single resonance in its 31P NMR spectrum at δ = –6.1
ppm, representing the triarylphosphine moieties. Polymer 8
in diethyl ether, MeOH, and hexanes. The loading levels of
the amine and phosphine groups of 8 were determined by
elemental analysis to be 7.5 and 1.9 mmol/g, respectively.
With 8 in hand, we next examined its use as a bifunc-
tional reagent in one-pot Wittig reactions. As illustrated in
Scheme 1, in these reactions the phosphine moieties of 8
react with activated alkyl halides 13 to form phosphonium
salt 14. The amine groups then deprotonate the phosphoni-
um salt groups to form the ylide groups of 15. Finally these
phosphorane groups react with the aldehyde substrate 16
to form polymeric byproduct 17 and the desired alkene
flexible functionalized grafts
heterogeneous
core
O
N
n
n
5n
R
rasta resin
PPh2
1: R = H
2: R = CH2NEt2
3: R = CH2N(i-Pr)2
Figure 1 Phosphine functionalized rasta resins 1–3
most recently, 7 has been prepared and used as a catalyst
for Henry reactions.18 Herein, we report the synthesis of bi-
functional PEI-supported triphenylphosphine (PEI-TPP, 8;
Scheme 1), and its use in a wide range of one-pot Wittig re-
actions that afforded high yields of the pure products after
simple separation of the polymeric byproduct.
NH2
O
NH2
HN
N
NH
N
N
H
NH2
H
H
N
N
N
n
n
O
H2N
N
N
NH2
H
H
NH2
N
NH
n
NH
NH
N
H
O
N
n
H2N
NH2
n
O
O
polyethyleneimine (4)
ULTRAMINE (6): scavenger reagent
H
H
H
N
N
N
HN
N
H
N
H
H
N
Ph
HN
Ph
HN
H
H
N
N
N
Ph
Ph
N
H
N
H
N
H
H
N
N
N
N
N
H
N
N
H
H
N
H
N
H
n
Ph
N
NH
N
HN
H
N
H
N
N
H
Ph
polyamine (7): catalyst for Henry reaction
Ultraresin (5): carrier for peptide synthesis, reagents and catalysts
Figure 2 PEI and various derivatives
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1737–1743

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X. Xia, P. H. Toy
Letter
Synlett
products 18–20. It is noteworthy that the byproduct am-
monium salt and phosphine oxide groups are both immobi-
lized on the polymer support, and thus should be separable
from the desired alkene product by a simple filtration oper-
ation, eliminating the need for an aqueous workup and
chromatographic purification.
We first used ethyl bromoacetate (13a) and ethyl 2-bro-
mopropionate (13b) as the activated alkyl halides in one-
pot Wittig reactions with aldehydes 16A–Q. These reac-
tions were performed homogeneously using conditions
similar to those we have used before12 (CHCl3 at 65 °C; Table
1).20 At the end of each reaction, the cooled reaction mix-
ture was poured into a mixture of diethyl ether and hexane
to induce precipitation of 17. After filtration and solvent
evaporation, the desired product was obtained as the ex-
pected mixture of E and Z isomers. When 13a was used,
18Aa–Qa were all obtained in excellent yields with typical
E/Z ratios. Importantly, all products were found to be essen-
1
tially pure diastereomeric mixtures according to H NMR
analysis, and did not require any additional purification. As
can be seen in Table 1, unsubstituted aromatic aldehydes
(entries 1 and 2), electron-rich aromatic aldehydes (entries
3 and 4), electron-poor aromatic aldehydes (entries 5–12),
heteroaromatic aldehydes (entries 13 and 14), alkyl alde-
hydes (entries 15 and 16), and even cinnamaldehyde (entry
17) all worked very well in these reactions. Similarly, ester
13b was used to synthesize trisubstituted alkenes 18Cb,
18Fb, and 18Ob, and these products were also highly pure
after precipitation of 17, filtration, and solvent removal.
O
O
p-TsOH
HOCH2CH2OH
1. n-BuLi
2. ClPPh2
1. 4, NaBH3CN, HCl
2.MeCHO, NaBH3CN
CHO
CHO
O
O
p-TsOH
PhMe, reflux
88%
THF, –78 °C
75%
THF–H O, reflux
2
MeOH
88%
Ph2P
Br
Br
Ph2P
70%
12
9
10
11
O
R2
R3
Ph2P
O
O
XPh2P
R2
XPh2P
R2
PPh2X
R3
R3
Ph2P
PPh2
N
N
N
N
O
N
N
X
R3
N
N
N
R2
13a–e
H+
N
N
N
N
N
N
N
N
N
N
N
transfer
N
n
N
N
N
N
N
n
Ph2P
PPh2
8
XPh2P
PPh2X
R2
14
R3
R3
R2
O
O
O
R2
R3
O
O
O
Ph2P
R2
Ph2P
R2
Ph2P
R3
R3
O
Ph2P
O
PPh2
PPh2
H
N
N
H
N
N
X
N
N
O
X
R1
16
H
O
H
N
N
N
H
N
H
N
N
N
H
H
H
N
N
N
+
X
X
X
N
N
N
N
N
R1
R3
X
X
X
R2
H
H
N
N
N
n
18–20
X
n
N
N
X
Ph2P
R2
PPh2
R2
Ph2P
O
PPh2
15
R3
R3
17
O
O
O
Scheme 1 Synthesis of 8 and its application in one-pot Wittig reactions
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1737–1743

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X. Xia, P. H. Toy
Letter
Synlett
Table 1 One-Pot Wittig Reactions Using α-Bromoestersa
Table 1 (continued)
Entry Product
Yield (%) E/Zb
O
Br
O
OEt
Cl
O
O
10
18Ja
18Ka
18La
92
91:9
93:7
92:8
OEt
13a
8
+
or
R1
H
R1
OEt
CHCl3, 65 °C
Cl
R2
O
O
Br
16
OEt
18
O2N
11
100
98
OEt
OEt
13b
R2 = H, Me
Yield (%) E/Zb
Cl
Entry Product
O
O2N
O
12
1
18Aa
94
92
89:11
OEt
O
Cl
O
13
18Ma
18Na
97
95
92:8
OEt
OEt
2
18Ba
18Ca
95:5
OEt
N
O
O
O
O
14
90:10
3
92
86
80:20
OEt
OEt
O
MeO
15
16
17
18Oa
18Pa
18Qa
98
97
95
91:9
91:9
87:13
OEt
MeO
4
18Da
91:9
O
MeO
n-C7H15
OEt
O
OMe
O
O
5
18Ea
18Fa
18Ga
18Ha
18Ia
95
95
93:7
OEt
OEt
OEt
Cl
O
18
18Cb
98
93:7
6
87:13
74:26
96:4
OEt
MeO
Br
O
O
19
20
18Fb
99
95
95:5
OEt
7
8
97
OEt
Br
Br
O
O
18Ob
>99:1
OEt
100
97
OEt
O2N
a Reaction conditions: 16 (0.2 mmol), 13a or 13b (0.3 mmol), 8 (0.4 mmol),
CHCl3 (1 mL), 65 °C.
Cl
O
b Determined by 1H NMR spectroscopic analysis.
9
>99:1
OEt
Cl
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1737–1743

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X. Xia, P. H. Toy
Letter
Synlett
We then used α-bromo amide 13c12a (Table 2) and α-
bromo ketones 13d and 13e (Table 3) as the alkyl halide to
perform the one-pot Wittig reactions. For the reactions us-
ing 13c–e, we chose a random sample from the aldehydes
used in Table 1. Additionally, for reactions with 13c we also
used aldehydes 16R and 16S (Table 2, entries 10 and 11).
Regardless of which alkyl halide and aldehyde combination
we studied, in all cases, excellent yield of highly pure prod-
uct was obtained after only precipitation of 17, filtration,
and solvent removal.
Table 2 (continued)
Entry Product
Yield (%) E/Zb
O
8
9
19Pc
19Qc
19Rc
19Sc
95
96
87
95
84:16
92:8
95:5
96:4
n-C7H15
N
O
N
Table 2 One-Pot Wittig Reactions Using an α-Halo Amidea
O
O
O
10
11
O
O
O
N
8
Br
+
R1
H
N
R1
N
CHCl3, 65 °C
O
16
13c
19
Br
N
Entry Product
Yield (%) E/Zb
a Reaction conditions: 16 (0.2 mmol), 13c (0.3 mmol), 8 (0.4 mmol), CHCl3
(1 mL), 65 °C.
O
O
b Determined by 1H NMR spectroscopic analysis.
1
N
N
19Cc
19Dc
93
98
96:4
MeO
Finally, since our group has an interest in studying tan-
dem reactions in which the waste of an initial reaction cata-
lyzes a subsequent transformation, we were also interested
in evaluating the reactivity of 8 in one-pot Wittig reactions
that were followed immediately by conjugate reduction re-
actions catalyzed by the phosphine oxide waste.21–23 In
these reactions, 13d was used as the substrate to react with
16A and 16F (Table 4).24 The α,β-unsaturated alkenes gen-
erated in the Wittig reactions (20Ad and 20Fd, respectively)
were treated with SiCl3 in situ. Activation of this reductant
by the phosphine oxide groups of 17 effected conjugate re-
duction to afford the final ketone products 21Ad and 21Fd.
Gratifyingly, excellent yield was obtained in both cases and
the product that was obtained directly from the reaction
mixture was essentially pure.
In conclusion, we have used commercially available
polymer 4 to prepare bifunctional reagent 8 bearing both
phosphine and tertiary amine groups, and successfully ap-
plied this material in a wide range of one-pot Wittig reac-
tions from which the desired product could be obtained in
high yield and purity after only precipitation of the waste,
filtration, and solvent removal. Reagent 8 has an advantage
compared to our previously reported bifunctional polymer-
ic reagents 2 and 3 because it is much more densely func-
tionalized, and thus reactions involving it require less re-
agent and solvent. We are currently studying the applica-
tion of 8 in other reactions, and the possibility of preparing
a cross-linked version of it that can function as a heteroge-
MeO
2
94:6
MeO
OMe
O
3
19Fc
19Hc
19Jc
94
96:4
94:6
97:3
N
Br
O
4
100
94
N
O2N
O
Cl
5
N
Cl
O
6
19Mc
19Oc
98
95
97:3
N
N
O
7
81:19
N
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1737–1743

1742
X. Xia, P. H. Toy
Letter
Synlett
neous reagent so the precipitation step can be eliminated
and recycling might be possible. The results of these studies
will be reported shortly.
Table 4 Tandem One-Pot Wittig/Conjugate Reduction Reactionsa
CHO
R
Table 3 One-Pot Wittig Reactions Using α-Halo Ketonesa
O
1. 8, 65 °C
2. HSiCl3, 0 °C to r.t.
16
O
+
R
CHCl3
Br
O
Br
Br
O
O
21
Br
13d
8
+
R1
H
R1
R2
or
Br
CHCl3, 65 °C
20
13d
O
Cl
16
Entry
1
Product
Yield (%)
13e
O
Entry Product
Yield E/Zb
(%)
21Ad
21Fd
85
90
Br
O
O
1
20Ad
95
93
>99:1
>99:1
2
Br
Br
Br
O
a Reaction conditions: 16 (0.2 mmol), 13d (0.3 mmol), 8 (0.4 mmol), CHCl3
(1 mL), 65 °C, followed by HSiCl3 (0.4 mmol), 0 °C to r.t.
2
20Fd
Br
Br
O
Acknowledgment
3
20Hd
96
95
99
99
92:8
95:5
98:2
92:8
This research was supported financially by the University of Hong
Kong and the Research Grants Council of the Hong Kong S. A. R, P. R. of
China (Project No. HKU 705510P).
O2N
Br
O
Supporting Information
4
5
6
20Pd
20Fe
20Me
n-C7H15
Supporting information for this article is available online at
Br
http://dx.doi.org/10.1055/s-0034-1380810.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
o
nrtogI
f
rmoaitn
O
References and Notes
Br
(1) Wittig, G.; Geissler, G. Justus Liebigs Ann. Chem. 1953, 580, 44.
(2) For selected recent reviews regarding the Wittig reaction, see:
(a) Parvatkar, P. T.; Torney, P. S.; Tilve, S. G. Curr. Org. Synth.
2013, 10, 288. (b) Byrne, P. A.; Gilheany, D. G. Chem. Soc. Rev.
2013, 42, 6670.
(3) Constable, D. J. C.; Dunn, P. J.; Hayler, J. D.; Humphrey, G. R.;
Leazer, J. L. Jr.; Linderman, R. J.; Lorenz, K.; Manley, J.; Pearlman,
B. A.; Wells, A.; Zaks, A.; Zhang, T. Y. Green Chem. 2007, 9, 411.
(4) For reviews of polymer-supported phosphines and their uses,
see: (a) Guino, M.; Hii, K. K. Chem. Soc. Rev. 2007, 36, 608.
(b) Bergbreiter, D. E.; Yang, Y.-C.; Hobbs, C. E. J. Org. Chem. 2011,
76, 6912.
(5) (a) Camps, F.; Castells, J.; Font, J.; Vela, F. Tetrahedron Lett. 1971,
1715. (b) McKinley, S. V.; Rakshys, J. W. J. Chem. Soc., Chem.
Commun. 1972, 134. (c) Heitz, W.; Michels, R. Angew. Chem., Int.
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Tetrahedron Lett. 1980, 21, 1375. (e) Akelah, A. Eur. Polym. J.
1982, 18, 559. (f) Bernard, M.; Ford, W. T. J. Org. Chem. 1983, 48,
O
N
O
7
8
20Oe
20Pe
94
97
92:8
97:3
O
n-C7H15
a Reaction conditions: 16 (0.2 mmol), 13d or 13e (0.3 mmol), 8 (0.4 mmol),
CHCl3 (1 mL), 65 °C.
b Determined by 1H NMR spectroscopic analysis.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1737–1743

1743
X. Xia, P. H. Toy
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Synlett
326. (g) Bernard, M.; Ford, W. T.; Nelson, E. C. J. Org. Chem. 1983,
48, 3164. (h) Sieber, F.; Wentworth, P. Jr.; Toker, J. D.;
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reactions, see: (a) Shimojuh, N.; Imura, Y.; Moriyama, K.; Togo,
H. Tetrahedron 2011, 67, 951. (b) Lebel, H.; Davi, M.; Roy, M.-N.;
Zeghida, W.; Charette, A. B. Synthesis 2011, 2275.
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(19) See the Supporting Information.
(20) General Procedure for One-Pot Wittig Reactions: Polymer 8
(0.2 g, 0.4 mmol phosphine) was dissolved in CHCl3 (1 mL) in a
10-mL round-bottomed flask equipped with a magnetic stirrer
and a reflux condenser, and 13 (0.3 mmol) and 16 (0.2 mmol)
were added. The mixture was stirred at 65 °C until the reaction
was determined to be complete by TLC or 1H NMR analysis. The
reaction mixture was then cooled to r.t. and poured into a
mixture of Et2O (10 mL) and hexane (30 mL) in a beaker. The
flask was rinsed with additional Et2O (10 mL), and the com-
bined organic solution was allowed to stand for 10 min before it
was filtered through a short pad of diatomaceous earth, using
additional Et2O (2 × 10 mL) for rinsing. The filtrate was concen-
trated under reduced pressure to afford the desired product in
an essentially pure state based on 1H NMR analysis.
(8) For a review on organic polymer supports for organic chemis-
try, see: Lu, J.; Toy, P. H. Chem. Rev. 2009, 109, 815.
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2011, 551. (b) Lu, J.; Toy, P. H. Synlett 2011, 659. (c) Lu, J.; Toy, P.
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(b) Teng, Y.; Lu, J.; Toy, P. H. Chem. Asian J. 2012, 7, 351.
(13) For the use of the oxides of 1 and 3 as reagent precursors in a
wide range of halogenation reactions, see: Xia, X.; Toy, P. H. Beil-
stein J. Org. Chem. 2014, 10, 1397.
(14) Various structures have been used to represent 4 in a range of
publications. Since we used 4 purchased from the Aldrich
Chemical Co., we use the structure shown in its catalogue.
(15) Haimov, A.; Cohen, H.; Neumann, R. J. Am. Chem. Soc. 2004, 126,
11762.
Ethyl Cinnamate (8Aa): 1H NMR (400 MHz, CDCl3): δ = 7.79 (d,
J = 16.0 Hz, 1 H), 7.53–7.51 (m, 2 H), 7.38–7.37 (m, 3 H), 6.44 (d,
J = 16.0 Hz, 1 H), 4.26 (q, J = 7.1 Hz, 2 H), 1.34 (t, J = 7.1 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 167.1, 144.7, 134.6, 130.3, 129.0,
128.2, 118.4, 60.6, 14.4. MS: m/z calcd for C11H12O2: 176.1;
found: 176.1.
(21) Lu, J.; Toy, P. H. Chem. Asian J. 2011, 6, 2251.
(22) For similar reactions studied by others and the inspiration for
our research in this area, see: (a) Sugiura, M.; Sato, N.; Kotani, S.;
Nakajima, M. Chem. Commun. 2008, 4309. (b) Cao, J.-J.; Zhou, F.;
Zhou, J. Angew. Chem. Int. Ed. 2010, 49, 5096. (c) Chen, L.; Shi, T.
D.; Zhou, J. Chem. Asian J. 2013, 8, 556. (d) Chen, L.; Du, Y.; Zeng,
X.-P.; Shi, T.-D.; Zhou, F.; Zhou, J. Org. Lett. 2015, 17, 1557.
(23) For a recent example of another reaction system in which a by-
product of one reaction catalyzes a subsequent transformation,
see: Zhu, F.; Xu, P.-W.; Zhou, F.; Wang, C.-H.; Zhou, J. Org. Lett.
2015, 17, 972.
(24) General Procedure for Tandem Wittig/Conjugate Reduction
Reactions: The Wittig reaction was conducted as before,[20] but
when it was determined to be complete, the mixture was
cooled to 0 °C in an ice-water bath, and HSiCl3 (0.4 mmol) was
added. The reaction mixture was stirred for 2 h at 0 °C and then
warmed to room temperature. When the reaction was deter-
mined to be complete by TLC analysis, the excess HSiCl3 and
solvent were evaporated under reduced pressure. The resulting
mixture was dissolved in CHCl3 (20 mL) and then added to sat.
aq Na2CO3 (20 mL). The mixture was stirred for 30 min, then the
aqueous phase was separated and washed with CH2Cl2 (3 × 15
mL). The combined organic layer was dried over MgSO4 and
concentrated under reduced pressure to afford the desired
product in an essentially pure state based on 1H NMR analysis.
1-(4-Bromophenyl)-3-phenylpropan-1-one (21Ad): 1H NMR
(400 MHz, CDCl3): δ = 7.82 (d, J = 8.6 Hz, 2 H), 7.59 (d, J = 8.6 Hz,
2 H), 7.30–7.21 (m, 5 H), 3.26 (t, J = 7.5 Hz, 2 H), 3.06 (t, J =
7.5 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ = 198.3, 141.1, 135.6,
132.0, 129.6, 128.7, 128.5, 128.3, 126.3, 40.5, 30.1. MS: m/z
calcd for C15H13BrO: 288.0; found 288.2.
(16) (a) Rademann, J.; Barth, M. Angew. Chem. Int. Ed. 2002, 41, 2975.
(b) Barth, M.; Rademann, J. J. Comb. Chem. 2004, 6, 340.
(c) Barth, M.; Tasadaque, S.; Shah, A.; Rademann, J. Tetrahedron
2004, 60, 8703. (d) Barth, M.; Fischer, R.; Brock, R.; Rademann, J.
Angew. Chem. Int. Ed. 2005, 44, 1560.
(17) Roice, M.; Christensen, S. F.; Meldal, M. Chem. Eur. J. 2004, 10,
4407.
(18) Ganesan, S. S.; Ganesan, A.; Kothandapani, J. Synlett 2014, 25,
1847.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1737–1743