Copper-catalyzed domino homologation and cycloisomerization reactions for 3-pyrroline synthesis

Article abstract of DOI:10.1002/ejoc.201301621

Copper bromide was found to be an efficient catalyst for a domino reaction sequence leading to 3-pyrrolines. The Cu(I)-catalyzed Crabbe reaction of propargyl sulfonamide and selective cycloisomerization of the allene intermediate were carried out using microwave irradiation conditions affording a wide range of 2-substituted- and 2,5-disubstituted-3-pyrrolines. Mechanistic studies of the reaction intermediates revealed two possible reaction pathways; both invoke the importance of vinyl copper intermediates.

Full text of DOI:10.1002/ejoc.201301621

FULL PAPER
DOI: 10.1002/ejoc.201301621
Copper-Catalyzed Domino Homologation and Cycloisomerization Reactions
for 3-Pyrroline Synthesis
Ye Ho Shin,[a][‡] Muchchintala Maheswara,[a][‡] Joon Young Hwang,[a] and Eun Joo Kang*[a]
Keywords: Synthetic methods / Domino reactions / Cyclization / Nitrogen heterocycles / Copper / Allenes
Copper bromide was found to be an efficient catalyst for a
domino reaction sequence leading to 3-pyrrolines. The Cu(I)-
catalyzed Crabbé reaction of propargyl sulfonamide and se-
lective cycloisomerization of the allene intermediate were
carried out using microwave irradiation conditions affording
a wide range of 2-substituted- and 2,5-disubstituted-3-
pyrrolines. Mechanistic studies of the reaction intermediates
revealed two possible reaction pathways; both invoke the im-
portance of vinyl copper intermediates.
α-amino allenes; potassium carbonate was found to mediate
5-endo cycloisomerization under refluxing DMF condi-
tions.[9] As part of our ongoing interest in economical dom-
ino reactions, we predicted that, as a general precursor of
allene,[10] terminal alkynes might be transformed to 3-
pyrrolines by the dual process of allene formation and sub-
sequent cycloisomerization.
Introduction
Nitrogen heterocycles, such as pyrroles, pyrrolines, and
pyrrolidines, are important structural elements in a large
number of natural products and pharmaceutical molecules;
many synthetic routes have been developed for their ef-
ficient preparation.[1] Among these nitrogen heterocycles,
pyrrolines have found outstanding utility in enabling syn-
thetic applications such as; (i) generation of pyrroles by oxi-
dation, (ii) conversion to pyrrolidines by reductive reac-
tions, and (iii) further olefin functionalizations by addition
reactions, to name just a few.[2] Substantial effort has been
invested to develop synthetic approaches to 3-pyrrolines,
rather than 1- or 2-pyrrolines. Olefin metathesis emerged
early on as one of the most powerful reactions for preparing
cycloalkenes. Initial ring-closing metathesis of diallylamine
was used to generate 3-pyrrolines by Grubbs in 1992,[3] and
chiral allylamine prepared by enantioselective allylic amin-
ation afforded substituted chiral pyrrolines.[4] Phosphine-
catalyzed [3 + 2] cycloadditions of 2,3-butadienoates and
imines were developed to afford corresponding 3-pyrroline-
3-carboxylate cycloadducts.[5] Other cyclization approaches
using a nitrogen nucleophile in α-amino allenes were re-
ported starting in 1999, and selective 5-endo cyclizations
were performed in silver- and gold-catalyzed intramolecular
hydroamination reactions (Scheme 1).[6,7] Palladium-cata-
lyzed cyclization reactions were found to become cascade
reactions introducing concurrent aryl, acyl, or allyl substit-
uents at the C-3 position of pyrrolines through the agency
of π-allyl palladium intermediates.[6a,6b,8] In the absence of
transition metal catalysts, 3-pyrrolines were produced from
Scheme 1. 5-endo cyclization of α-amino allenes for 3-pyrroline syn-
thesis.
For allene synthesis from terminal alkynes, copper salts
have been broadly used in the Crabbé reaction.[10a,10b]
Furthermore, copper-catalyzed cycloisomerization reac-
tions of allenes have been reported to yield various hetero-
cycles, such as butenolides and dihydrofurans.[11] In connec-
tion with copper dual catalysis, Tanaka and co-workers ob-
served that propargyl tosylamide, under Crabbé conditions,
afforded an intractable mixture of allene and pyrroline in
35% yield.[12] Although they did not place much emphasis
on this in their report, the choice of tertiary amine (diiso-
propylethylamine) appears to have an impact on conversion
yields. In this paper, we present a full account of our investi-
[a] Department of Applied Chemistry, Kyung Hee University,
Yongin, Gyeonggi, 446-701, Korea
E-mail: ejkang24@khu.ac.kr
http://orgchem.khu.ac.kr
[‡] These authors contributed equally to this work.
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301621.
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Y. H. Shin, M. Maheswara, J. Y. Hwang, E. J. Kang
FULL PAPER
gations into the one-pot synthesis of 3-pyrrolines from alk-
ynes using copper catalysis.
Results and Discussion
To examine the prospect of using propargylamines as po-
tential substrates, propargyl sulfonamide (1a) and formal-
dehyde were used, in the presence of CuI to create 3-pyrro-
line heterocycles; dialkylamine served as the H source.[10b]
As described in Table 1, the copper iodide and diisopropyl-
amine system smoothly promoted allene formation at
100 °C, a lower temperature than typically called for by ge-
neral Crabbé conditions for allene synthesis (130–150 °C).
Mild heating afforded allene 2a in 56% yield, accompanied
by remaining sulfonamide. When the reaction was carried
out at higher reaction temperatures using microwave irradi-
ation,[10c] a dramatic change occurred leading to allene for-
mation followed by selective 5-endo cyclization of allene 2a
within 3 h. The halide effects of copper salts were next ex-
amined and copper bromide was found to be the most ef-
ficient catalyst when considering conversion yields and
product ratios for desired adduct 3a. The purity of copper
salts also affected conversion yields (10–20% lower). Conse-
quently, commercial catalysts were dried before use. Treat-
ment with dicyclohexylamine instead of diisopropylamine
gave higher yields for conversion of 1a and consecutive cy-
clization of 2a.[10b] Copper bromide proved to be superior
to other copper and zinc catalysts (Table 1, Entries 6–12).
Diminished amounts of catalyst proved insufficient for ef-
fecting cycloisomerization of 2a to give 3a. Increasing cata-
lyst concentrations reduced reaction times but also led to
slight decreases in isolated yield.
Scheme 2. Synthesis of 3-pyrroline; substrate scope; reactions and
conditions: propargyl amide (1, 0.33 mmol), (CH2O)n (2.0 equiv.),
CuBr (0.4 equiv.), cHex2NH (2.0 equiv.), dioxane (0.15 m) under
microwave irradiation conditions, unless otherwise specified. [a] Re-
action with CuI and iPr2NH. [b] Reaction with CuI.
required propargylamines was straightforward and per-
formed by alkynylation of aldehydes followed by either Mit-
sunobu-type amidation with TsNHBoc or Fe-catalyzed am-
ination with TsNH2. Various N-nucleophiles were investi-
gated with sulfonamide, carbamate, and benzylamine func-
tional groups. Substituted benzenesulfonamides reacted to
afford the corresponding 3-pyrrolines without any prob-
lems, whereas benzenesulfonamides with sterically hindered
trimethyl substituents and electron-withdrawing nitro
groups were generated in moderate yields. Unfortunately,
carbamate substrates gave intractable product mixture that
failed to contain allenes or pyrrolines. The benzylamine
substrate directly afforded N-benzyl pyrrole in low yield
(6%). Alkyl-substituted secondary amides were also tested
in the 2-alkyl-3-pyrroline yielding procedures. Methyl-, iso-
propyl-, and cyclopropyl-substituted propargyl sulfon-
amides were subjected to domino allene formation and se-
lective hydroamination under the above conditions, produc-
ing 3i–k in 72–99% yields. The optically pure secondary
amide was also transformed into (R)-2-methyl-3-pyrroline
(3i) without depleting its chiral purity (99% ee). 2-Phenyl-
3-pyrroline (3l) was obtained from 1-phenyl-2-propynyl
sulfonamide and copper catalyst in 95% yield. The presence
Table 1. Optimization of conditions for 3-pyrroline synthesis.[a]
Entry Catalyst
Amine
Temp. [°C] Yield [%]
2a/3a
1
2
3
4
5
6
7
8
CuI
CuI
CuI
iPr2NH
iPr2NH
iPr2NH
iPr2NH
100[b]
130
180
180
180
180
180
180
180
180
180
180
180
180
56
91
84
85
68
95
95
91
57
60
60
29
90
84
2a only
4.5:1
1.3:1
0.8:1
0.1:1
0.2:1
3a only
0.1:1
0.7:1
2.0:1
1.3:1
33:1
0.6:1
3a only
CuBr
CuCl
CuI
CuBr
CuCl
CuBr2
Cu(OAc)2 cHex2NH
Cu(OTf)2 cHex2NH
ZnBr2
CuBr
CuBr
iPr2NH
cHex2NH
cHex2NH
cHex2NH
cHex2NH
9
10
11
12
13[c]
14[d]
cHex2NH
cHex2NH
cHex2NH
[a] Reactions and conditions: propargyl amide (1a, 0.33 mmol),
(CH2O)n (2.0 equiv.), catalyst (0.4 equiv.), amine (2.0 equiv.), diox- of electron-donating groups on the phenyl group led to
ane (0.15 m) under microwave irradiation conditions for 3 h, unless
lower yields of the 3-pyrroline products, and substrates with
otherwise specified. [b] Reaction under reflux. [c] Reaction with
biphenyl and m-iodophenyl groups required modified con-
0.2 equiv. of CuBr. [d] Reaction under 0.25 m of solution.
ditions exploiting copper iodide (instead of CuBr) for ef-
Encouraged by these initial results, the generality of this ficient conversion. Compounds containing the haloarene
process was further explored (Scheme 2). Preparation of the moiety, such as 2-(3-iodophenyl)- and 2-(4-bromophenyl)-
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3-Pyrroline Synthesis by Copper-Catalyzed Domino Reactions
3-pyrroline (3p and 3q), are well-known in assorted Pd- or
Ir-catalyzed coupling reactions.[13] One substrate bearing
the conjugated alkene functional group was recalcitrant to
participation in the desired cyclization reaction. For this re-
action, as represented by generation of 3r (Scheme 2),
longer reaction time was needed (10 h) to achieve complete
conversion although the isolated yield was only 19%.[14]
Previous efforts aimed at disubstituted allene synthesis
used treatment of alkyl aldehydes, instead of formaldehyde,
as a way to introduce various substituents onto the 3-pyrro-
line scaffold. Sulfonamide 1a was subjected, under Ma’s
modified procedure, to nPrCHO and nBu2NH. Ma had de-
veloped a Cu-catalyzed 1,3-disubstituted allene synthesis
and established a dialkylamine effect.[10e] Consequently, the
reaction containing 1a, nPrCHO and nBu2NH afforded n-
propyl-substituted allene after which subsequent 5-endo cy-
clization furnished 2-propyl-3-pyrroline 4 (Table 2). These
conditions were then applied to methyl-substituted propar-
gyl sulfonamide 1i, and 2,5-dialkyl-substituted 3-pyrroline
5 was obtained as a diastereomeric mixture (cis/trans =
1.3:1) in good yield. Several 2,5-(alkyl/aryl)-disubstituted 3-
pyrrolines 6a–c were produced from phenyl-substituted pro-
pargyl sulfonamide 1l subjected to nPrCHO, iPrCHO and
EtCHO in moderate yields and diastereomeric ratios.
Scheme 3. Oxidative conversion of pyrrolines to pyrroles.
The domino reaction of 1a in dioxane and D2O gave rise
to corresponding deuterated product 3a in 86% yield with
45% d-incorporation, indicating that a vinyl copper inter-
mediate might be involved (Scheme 4). Time-dependent
TLC analysis and NMR experiments showed that the reac-
tion first generates 2a, which then disappears with concur-
rent formation of 3a.[17] The copper catalyst was presumed
to promote allene formation as well as cyclization. To deter-
mine if active catalyst was required in the cyclization reac-
tion of allene 2a, 5-endo cyclization of α-amino allene 2a
was conducted as a test case. Treatment of allene 2a with
CuBr led to smooth formation of 3-pyrroline 3a in quanti-
tative yield, except for when using Cy2NH. However, the
isolated yield of 3a did not exceed 50% even under lower
temperatures. We postulate, sased on these results, that 2a
acts as a substrate in the CuBr-catalyzed cyclization, and
that an alternative route for direct transformation of 1a to
3a is also possible under microwave irradiation conditions.
Table 2. 2,5-Disubstituted 3-pyrroline synthesis.[a]
Entry R1
R2
Amine
Product Yield [%][b]
1
2
3
4
5
6
H (1a)
nPr
nPr
nPr
nPr
iPr
Et
nBu2NH
nBu2NH
nBu2NH (2R)-5
nBu2NH 6a
iBu2NH 6b
nPr2NH 6c
4
5
95
Me (1i)
Me [(R)-1i]
Ph (1l)
68 (1.3:1)
58 (1.1:1)[c]
60 (1.6:1)
40 (3.3:1)
34 (1.3:1)
Ph (1l)
Ph (1l)
[a] Reactions and conditions: propargyl amide (0.33 mmol),
R2CHO (2.0 equiv.), CuBr (0.4 equiv.), amine (2.0 equiv.), dioxane
(0.15 m) under microwave irradiation. [b] Ratio of diastereoisomers
in parenthesis (cis/trans). [c] cis isomer with 98% ee; trans isomer
with 98% ee.
Subsequent studies on the aromatization of 3-pyrroline
compounds were undertaken to synthesize pyrrole deriva-
tives. Results shown in Scheme 3 suggest that product 3 can
be efficiently converted into pyrrole 7 by treatment with the
oxidant DDQ.[2a,5] In addition to simple pyrrole 7a, alkyl-
substituted pyrroles (7i and 7j) and aryl-substituted pyrroles
(7m and 7q) were obtained in good to excellent yields. It
is noteworthy that general pyrrole synthesis from pyrroline
Scheme 4. Mechanistic investigation of 3-pyrroline formation.
Figure 1 shows the proposed overall mechanism for
involved elimination of MeOH or H2O from either the CuBr-catalyzed reaction of propargyl sulfonamides. Inter-
methoxy- or alcohol-containing pyrrolines precursors.[15] action of the terminal alkyne with CuBr in the presence of
Our strategy proceeded in an outstanding atom-economic base forms alkynyl copper intermediate I, which then reacts
and redox-economic way. Although one report has been with in situ-generated iminium II to yield propargyl diamine
found regarding the Suzuki reaction affording 2-phenyl- III. Intramolecular hydride transfer yields vinyl copper in-
pyrrole,[16] alkyl substituents could not be introduced from termediate IV, and subsequent demetallation affords allene
2-bromopyrrole using cross-coupling reactions. Our strat- 2a with regeneration of CuBr. Cu(I)-catalyzed 5-endo cyclo-
egy offers an efficient two-step route to 2-alkyl-substituted isomerization of allene is initiated by Cu coordination to
pyrrole.
the less substituted allene terminus forming pyrrolidinyl
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Y. H. Shin, M. Maheswara, J. Y. Hwang, E. J. Kang
FULL PAPER
Figure 1. Proposed mechanism of Cu(I)-catalyzed 3-pyrroline synthesis.
forded 3a (71 mg, 95%), after column chromatography (hexane/
EtOAc, 10:1), m.p. 131 °C. H NMR (300 MHz, CDCl3): δ = 7.72
(d, J = 8.0 Hz, 2 H), 7.32 (d, J = 8.0 Hz, 2 H), 5.65 (s, 2 H), 4.12
(4 H, S), 2.43 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 143.4,
134.3, 129.8, 127.4, 125.4, 54.8, 21.5 ppm. HRMS (EI): calcd. for
C11H13NO2S [M]+ 223.0667, found 223.0666.
copper intermediate VI. Demetallation of IV affords 3-
pyrroline 3a. Alternative routes are also possible in which
vinyl copper isomerization from IV to IVЈ is followed by
cyclization to copper intermediate VI with a liberated imine
group.[18]
1
1-(Mesitylsulfonyl)-3-pyrroline (3b): The reaction of 1b (70 mg,
0.27 mmol), CuBr (16 mg, 0.12 mmol), p-formaldehyde (17 mg,
0.58 mmol), and dicyclohexylamine (0.10 mL, 0.58 mmol) in diox-
Conclusions
The CuBr-catalyzed domino reaction of propargyl ane (2 mL) afforded 3b (33 mg, 45%), after column chromatog-
raphy (hexane/EtOAc, 10:1). 1H NMR (300 MHz, CDCl3): δ = 6.95
sulfonamide was developed to afford a range of 2-substi-
tuted and 2,5-disubstituted-3-pyrrolines under microwave
conditions. Of particular significance, this is the first report
of a copper catalyst that ties in the Crabbé reaction with
further transformations. Furthermore, this domino chemis-
try highlights the significant utility of allenes in Cu(I)-cata-
(s, 2 H), 5.74 (s, 2 H), 4.09 (s, 4 H), 2.63 (s, 6 H), 2.30 (s, 3 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 142.4, 140.1, 132.8, 131.8, 125.3,
53.6, 22.8, 20.9 ppm. HRMS (EI): calcd. for C13H17NO2S [M]+
251.0980, found 251.0986.
1-[(4-Methoxyphenyl)sulfonyl]-3-pyrroline (3c):[20] The reaction of
1c (70 mg, 0.31 mmol), CuBr (18 mg, 0.12 mmol), p-formaldehyde
(19 mg, 0.62 mmol), and dicyclohexylamine (0.12 mL, 0.62 mmol)
in dioxane (2 mL) afforded 3c (68 mg, 92%), after column
chromatography (hexane/EtOAc, 10:1), m.p. 105 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.78 (d, J = 8.8 Hz, 2 H), 6.99 (d, 2 H,
8.8 Hz), 5.65 (s, 2 H), 4.11 (s, 4 H) 3.87 (s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 162.9, 129.5, 129.0, 125.4, 114.3, 55.6,
54.8 ppm. HRMS (EI): calcd. for C11H13NO3S [M]+ 239.0616,
found 239.0613.
lyzed heterocycle synthesis. The alkyl and aryl-substituted
pyrrolines are versatile synthetic intermediates and can be
easily transformed into pyrrole derivatives in a highly atom-
economical way. Owing to the usefulness of the products
and the easy availability of various propargylamines, this
reaction has the potential to be tremendously useful in N-
heterocyclic chemistry.
1-([1,1Ј-Biphenyl]-4-ylsulfonyl)-3-pyrroline (3d): The reaction of 1d
(70 mg, 0.26 mmol), CuBr (15 mg, 0.10 mmol), p-formaldehyde
(15 mg, 0.52 mmol), and dicyclohexylamine (0.10 mL, 0.52 mmol)
in dioxane (1.7 mL) afforded 3d (56 mg, 75%), after column
chromatography (hexane/EtOAc, 10:1), m.p. 144 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.90 (d, J = 8.0 Hz, 2 H), 7.73 (d, J =
8.4 Hz, 2 H) 7.60 (d, J = 7.6 Hz, 2 H), 7.51–7.41 (m, 3 H), 5.68 (s,
2 H), 4.17 (s, 4 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 145.5,
139.2, 135.7, 129.0, 128.4, 127.8, 127.7, 127.2, 125.4, 54.8 ppm.
HRMS (EI): calcd. for C16H15NO2S [M]+ 285.0823, found
285.0824.
Experimental Section
General Procedure for CuBr-Catalyzed Domino Reaction for 3-
Pyrroline Synthesis: To a solution of 4-methyl-N-(prop-2-yn-1-yl)-
benzenesulfonamide (70 mg, 0.33 mmol) in dioxane (2 mL) was
added p-formaldehyde (20 mg, 0.66 mmol), copper bromide
(19 mg, 0.13 mmol) and dicyclohexylamine (0.1 mL, 0.66 mmol).
After being stirred for 3 h under microwave irradiation (CEM Dis-
cover-908005 microwave reactor, 100 W, 175–180 °C measured by
external IR sensor), silica gel column chromatography provided 3-
pyrroline.
1-Tosyl-3-pyrroline (3a):[19] The reaction of 1a (70 mg, 0.33 mmol), 1-[(2-Nitrophenyl)sulfonyl]-3-pyrroline (3e):[20] The reaction of 1e
CuBr (19 mg, 0.13 mmol), p-formaldehyde (20 mg, 0.66 mmol),
(70 mg, 0.29 mmol), CuBr (16 mg, 0.12 mmol), p-formaldehyde
and dicyclohexylamine (0.09 mL, 0.66 mmol) in dioxane (2 mL) af-
(17 mg, 0.58 mmol), and dicyclohexylamine (0.12 mL, 0.58 mmol)
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3-Pyrroline Synthesis by Copper-Catalyzed Domino Reactions
in dioxane (2 mL) afforded 3e (44 mg, 59%), after column
chromatography (hexane/EtOAc, 7:1), m.p. 125 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.99–7.96 (m, 1 H) 7.74–7.68 (m, 2 H),
7.67–7.61 (m, 1 H) 5.78 (s, 2 H), 4.29 (d, 4 H) ppm. 13C NMR
0.62 mmol), and dicyclohexylamine (0.12 mL, 0.62 mmol) in diox-
ane (2 mL) afforded 3m (59 mg, 60%), after column chromatog-
raphy (hexane/EtOAc, 10:1). 1H NMR (300 MHz, CDCl3): δ = 7.52
(d, J = 8.1 Hz, 2 H), 7.19 (d, J = 8.4 Hz, 2 H), 7.14 (d, J = 8.1 Hz,
(75 MHz, CDCl3): δ = 133.5, 132.0, 131.7, 130.2, 125.2, 124.1, 2 H), 7.09 (d, J = 8.0 Hz, 2 H), 5.70 (dq, J = 6.1, 2.0 Hz, 1 H),
55.0 ppm. HRMS (EI): calcd. for C10H10N2O2S [M]+ 254.0361,
found 254.0365.
2-Methyl-1-tosyl-3-pyrroline (3i):[4a] The reaction of 1i (71 mg,
0.32 mmol), CuBr (18 mg, 0.13 mmol), p-formaldehyde (19 mg,
0.64 mmol), and dicyclohexylamine (0.13 mL, 0.64 mmol) in diox-
ane (2 mL) afforded 3i (58 mg, 72%), after column chromatography
(hexane/EtOAc, 10:1). 1H NMR (300 MHz, CDCl3): δ = 7.72 (d,
5.63 (dq, J = 6.3, 2.1 Hz, 1 H), 5.49–5.45 (m, 1 H), 4.36–4.21 (m,
2 H), 2.39 (s, 3 H), 2.33 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 143.1, 137.5, 135.4, 130.7, 129.4, 129.1, 127.3, 127.2, 124.3,
70.0, 55.4, 21.5, 21.1 ppm. HRMS (EI): calcd. for C18H19NO2S
[M]+ 313.1136, found 313.1139.
2-(4-Methoxyphenyl)-1-tosyl-3-pyrroline (3n):[22] The reaction of 1n
(70 mg, 0.22 mmol), CuBr (13 mg, 0.09 mmol), p-formaldehyde
J = 8.4 Hz, 2 H), 7.30 (d, J = 8.1 Hz, 2 H), 5.58–5.51 (m, 2 H), (13 mg, 0.44 mmol), and dicyclohexylamine (0.9 mL, 0.44 mmol) in
4.51–4.45 (m, 1 H), 4.21–4.04 (m, 2 H), 2.42 (s, 3 H) 1.41 (d, J = dioxane (1.5 mL) afforded 3n (24 mg, 33%), after column
6.2 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 143.3, 134.8,
131.5, 129.7, 127.4, 123.8, 63.1, 55.3, 22.9, 21.5 ppm. HRMS (EI):
calcd. for C12H15NO2S [M]+ 237.0823, found 237.0824. For (R)-3i,
the reaction of (R)-1i (48 mg, 0.21 mmol), CuBr (13 mg,
0.09 mmol), p-formaldehyde (13 mg, 0.43 mmol), and dicyclohex-
ylamine (0.08 mL, 0.43 mmol) in dioxane (1.4 mL) afforded (R)-
3i (35.2 mg, 71%), after column chromatography (hexane/EtOAc,
20:1). [α]D = –81.7 (c = 0.24, CHCl3); HPLC Chiralcel OJ-H col-
umn (99:1 hexanes/2-propanol, 1 mL/min) tR 43.9 min (minor),
46.7 min (major): 99% ee.
chromatography (hexane/EtOAc, 10:1), m.p. 119 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.48 (d, J = 8.4 Hz, 2 H), 7.16 (d, J =
7.0 Hz, 2 H), 7.14 (d, J = 8.4 Hz, 2 H), 6.78 (d, J = 8.4 Hz, 2 H),
5.76 (dq, J = 6.2, 2.2 Hz, 1 H), 5.61 (dq, J = 6.0, 2.0 Hz, 1 H),
5.48–5.45 (m, 1 H), 4.30 (dq, J = 14.5, 2.4 Hz, 1 H), 4.21 (ddt, J
= 14.6, 5.5, 2.0 Hz, 1 H), 3.77 (s, 3 H), 2.36 (s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 159.3, 143.0, 135.7, 132.6, 130.7, 129.4,
128.6, 127.2, 124.3, 113.8, 69.7, 55.3, 55.2, 21.5 ppm. HRMS (EI):
calcd. for C18H19NO3S [M]+ 329.1086, found 329.1085.
2-([1,1Ј-Biphenyl]-4-yl)-1-tosyl-3-pyrroline (3o): The reaction of 1o
(70 mg, 0.19 mmol), CuI (11 mg, 0.08 mmol), p-formaldehyde
(12 mg, 0.38 mmol), and diisopropylamine (0.08 mL, 0.38 mmol) in
dioxane (1.3 mL) afforded 3o (45 mg, 62%), after column
chromatography (hexane/EtOAc, 10:1), m.p. 143 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.51–7.35 (m, 8 H), 7.30–7.19 (m, 3 H),
7.11 (d, J = 8.4 Hz, 2 H), 5.77–5.73 (m, 1 H), 5.62 (dq, J = 6.2,
2.1 Hz, 1 H), 5.51–5.48 (m, 1 H), 4.35–4.18 (m, 2 H), 2.30 (s, 3
2-Isopropyl-1-tosyl-3-pyrroline (3j): The reaction of 1j (60 mg,
0.23 mmol), CuBr (14 mg, 0.09 mmol), p-formaldehyde (14 mg,
0.46 mmol), and dicyclohexylamine (0.09 mL, 0.46 mmol) in diox-
ane (1.5 mL) afforded 3j (60 mg, 99%), after column chromatog-
raphy (hexane/EtOAc, 10:1). 1H NMR (300 MHz, CDCl3): δ = 7.70
(d, J = 8.1 Hz, 2 H), 7. 29 (d, J = 8.4 Hz, 2 H), 5.67–5.63 (m, 1
H), 5.57–5.52 (m, 1 H), 4.41–4.36 (m, 1 H), 4.16–4.03 (m, 2 H),
2.41 (s, 3 H), 2.30–2.19 (m, 1 H), 0.94 (d, J = 7.0 Hz, 3 H), 0.84 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 143.1, 140.9, 140.8,
(d, J = 7.0 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 143.2,
134.9, 129.6, 127.3, 126.7, 125.9, 72.7, 56.1, 33.2, 21.5, 19.0,
16.0 ppm. HRMS (EI): calcd. for C14H19NO2S [M]+ 265.1136,
found 265.1141.
139.4, 135.6, 130.5, 129.4, 128.8, 127.8, 127.3, 127.3, 127.2, 127.1,
124.7, 69.9, 55.4, 21.5 ppm. HRMS (EI): calcd. for C23H21NO2S
[M]+ 375.1293, found 375.1293.
2-(3-Iodophenyl)-1-tosyl-3-pyrroline (3p): The reaction of 1p (64 mg,
0.15 mmol), CuI (9 mg, 0.06 mmol), p-formaldehyde (9 mg,
0.30 mmol), and dicyclohexylamine (0.06 mL, 0.30 mmol) in diox-
ane (1 mL) afforded 3p (49 mg, 76%), after column chromatog-
raphy (hexane/EtOAc, 10:1), m.p. 110 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.57–7.40 (m, 4 H), 7.26–7.18 (m, 3 H), 7.04–6.99 (m,
1 H), 5.84–5.79 (m, 1 H), 5.63–5.60 (m, 1 H), 5.45–5.42 (m, 1 H),
4.41–4.23 (m, 2 H), 2.40 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 143.4, 142.6, 136.8, 136.1, 135.5, 130.2, 130.1, 129.6, 127.1,
2-Cyclopropyl-1-tosyl-3-pyrroline (3k): The reaction of 1k (50 mg,
0.20 mmol), CuBr (11 mg, 0.08 mmol), p-formaldehyde (12 mg,
0.40 mmol), and dicyclohexylamine (0.08 mL, 0.40 mmol) in diox-
ane (1.3 mL) afforded 3k (33 mg, 84%), after column chromatog-
raphy (hexane/EtOAc, 10:1), m.p. 91 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.71 (d, J = 8.0 Hz, 2 H), 7.28 (d, J = 8.0 Hz, 2 H),
5.63 (dd, J = 6.2, 1.5 Hz, 1 H), 5.53 (dd, J = 6.2, 2.2 Hz, 1 H),
4.17–4.10 (m, 3 H), 2.41 (s, 3 H), 1.09–0.98 (m, 1 H), 0.57–0.42 (m,
3 H), 0.33–0.25 (m, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 126.8, 125.1, 94.4, 69.5, 55.4, 21.6 ppm. HRMS (EI): calcd. for
143.2, 135.6, 129.5, 128.9, 127.3, 125.2, 70.5, 55.6, 21.5, 16.3, 4.0,
1.6 ppm. HRMS (EI): calcd. for C14H17NO2S [M]+ 263.0980,
found 263.0964.
C17H16INO2S [M]+ 424.9946, found 424.9948.
2-(4-Bromophenyl)-1-tosyl-3-pyrroline (3q): The reaction of 1q
(50 mg, 0.14 mmol), CuBr (8 mg, 0.06 mmol), p-formaldehyde
(8 mg, 0.27 mmol), and dicyclohexylamine (0.05 mL, 0.27 mmol) in
dioxane (1 mL) afforded 3q (43 mg, 80%), after column
chromatography (hexane/EtOAc, 10:1), m.p. 143 °C. 1H NMR
(300 MHz, CDCl3): δ = 7.54 (d, J = 8.4 Hz, 2 H), 7.39 (d, J =
8.1 Hz, 2 H), 7.20 (d, J = 8.4 Hz, 2 H), 7.12 (d, J = 8.4 Hz, 2 H),
5.80 (dq, J = 6.1, 2.1 Hz, 1 H), 5.61 (dq, J = 6.3, 2.1 Hz, 1 H),
5.48–5.44 (s, 1 H), 4.34 (dq, J = 14.5, 2.4 Hz, 1 H), 4.25 (ddt, J =
2-Phenyl-1-tosyl-3-pyrroline (3l):[21] The reaction of 1l (43 mg,
0.15 mmol), CuBr (9 mg, 0.06 mmol), p-formaldehyde (9 mg,
0.30 mmol), and dicyclohexylamine (0.06 mL, 0.30 mmol) in diox-
ane (1 mL) afforded 3l (24 mg, 95%), after column chromatography
1
(hexane/EtOAc, 10:1), m.p. 131 °C. H NMR (300 MHz, CDCl3):
δ = 7.51 (d, J = 8.1 Hz, 2 H), 7.32–7.21 (m, 5 H), 7.19 (d, J =
8.4 Hz, 2 H) 5.79 (dq, J = 6.2, 1.8 Hz, 1 H), 5.65 (dq, J = 6.0,
2.0 Hz, 1 H), 5.54–5.50 (m, 1 H), 4.35 (dq, J = 14.6, 2.3 Hz, 1 H), 14.5, 5.3, 2.0 Hz, 1 H), 2.40 (s, 3 H) ppm. 13C NMR (75 MHz,
4.35 (ddt, J = 14.3, 5.5, 2.0 Hz, 1 H), 2.39 (s, 1 H) ppm. 13C NMR
CDCl3): δ = 143.4, 139.6, 135.4, 131.5, 130.1, 129.5, 129.0, 127.2,
(75 MHz, CDCl3): δ = 143.1, 140.4, 135.5, 130.6, 129.4, 128.4, 125.0, 121.8, 69.6, 55.4, 21.5 ppm. HRMS (EI): calcd. for
127.7, 127.24, 127.21, 124.5, 70.2, 55.4, 21.5 ppm. HRMS (EI):
C17H16BrNO2S [M]+ 377.0085, found 377.0083.
calcd. for C17H17NO2S [M]+ 299.0980, found 299.0981.
(E)-2-Styryl-1-tosyl-3-pyrroline (3r): The reaction of 1r (70 mg,
2-(p-Tolyl)-1-tosyl-3-pyrroline (3m): The reaction of 1m (70 mg, 0.22 mmol), CuBr (13 mg, 0.09 mmol), p-formaldehyde (14 mg,
0.31 mmol), CuBr (18 mg, 0.12 mmol), p-formaldehyde (18 mg, 0.45 mmol), and dicyclohexylamine (0.09 mL, 0.45 mmol) in diox-
Eur. J. Org. Chem. 2014, 2305–2311
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2309

Y. H. Shin, M. Maheswara, J. Y. Hwang, E. J. Kang
FULL PAPER
ane (1.5 mL) afforded 3r (14 mg, 19%), after column chromatog-
raphy (hexane/EtOAc, 10:1). 1H NMR (300 MHz, CDCl3): δ = 7.71
(d, J = 8.4 Hz, 2 H), 7.31–7.17 (m, 7 H), 6.56 (d, J = 15.8 Hz, 2
H), 5.98 (dd, J = 15.9, 7.5 Hz, 2 H), 5.75–5.72 (m, 1 H), 5.63–5.58
(m, 1 H), 5.14–5.11 (m, 1 H), 4.30–4.23 (m, 1 H), 4.22–4.12 (m, 1
H), 2.38 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 143.3,
136.3, 131.5, 129.6, 129.0, 128.5, 127.8, 127.5, 126.6, 125.3, 68.6,
55.0, 21.5 ppm. HRMS (EI): calcd. for C19H19NO2S [M]+
325.1136, found 325.1139.
(s, 2 H), 5.50 (s, 1 H), 4.39 (dd, J = 5.3, 2.4 Hz, 1 H), 2.41 (s, 3 H),
2.09–2.05 (m, 1 H), 1.03 (d, J = 6.9 Hz, 3 H), 0.83 (d, J = 7.0 Hz,
3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 143.4, 140.6, 134.8,
129.5, 129.3, 128.2, 127.7, 127.5, 127.1, 73.4, 70.3, 33.0, 21.5, 20.2,
17.5 ppm. HRMS (EI): calcd. for C20H23NO2S [M]+ 341.1449,
found 341.1444.
2-Ethyl-5-phenyl-1-tosyl-3-pyrroline (6c):[23] The reaction of 1l
(50 mg, 0.18 mmol), CuBr (10 mg, 0.07 mmol), propanaldehyde
(0.03 mL, 0.36 mmol), and di-n-propylamine (0.05 mL, 0.36 mmol)
in dioxane (1.2 mL) afforded 6c (15 mg, 34%) as a mixture of cis-6c
and trans-6c (1.3:1), after column chromatography (hexane/EtOAc,
20:1). For cis-6c, 1H NMR (300 MHz, CDCl3): δ = 7.64 (d, J =
8.4 Hz, 2 H), 7.33 (d, J = 8 Hz, 2 H), 5.76 (dq, J = 5.2, 1.3 Hz, 1
H), 5.64 (dq, J = 5.2, 1.3 Hz, 1 H), 5.47 (d, J = 2.2 Hz, 1 H), 4.49–
4.45 (m, 1 H), 2.40 (s, 3 H), 2.04–1.98 (m, 1 H), 1.73–1.63 (m, 1
H), 0.97 (t, J = 7.5 Hz, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 143.3, 140.9, 129.5, 129.2, 128.6, 127.60, 127.57, 127.2, 70.6, 69.4,
30.4, 21.5, 10.2 ppm. HRMS (EI): calcd. for C19H21NO2S [M]+
2-Propyl-1-tosyl-3-pyrroline (4):[22] The reaction of 1a (70 mg,
0.33 mmol), CuBr (19 mg, 0.13 mmol), n-butylaldehyde (0.06 mL,
0.66 mmol), and di-n-butylamine (0.11 mL, 0.66 mmol) in dioxane
(2 mL) afforded 4 (84 mg, 95%), after column chromatography
1
(hexane/EtOAc, 20:1), m.p. 85 °C. H NMR (300 MHz, CDCl3): δ
= 7.70 (d, J = 8.4 Hz, 2 H), 7.29 (d, J = 8.1 Hz, 2 H), 5.61–5.55
(m, 2 H), 4.50–4.43 (m, 1 H), 4.10 (d, J = 3.3 Hz, 2 H), 2.42 (s, 3
H), 1.82–1.65 (m, 2 H), 1.60–1.20 (m, 2 H), 0.93 (t, J = 7.3 Hz, 3
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 143.3, 129.8, 129.6,
127.4, 124.5, 67.3, 55.6, 38.3, 21.5 17.8, 14.1 ppm. HRMS (EI): 327.1293, found 327.1288.
calcd. for C14H19NO2S [M]+ 265.1136, found 265.1139.
General Procedure for Pyrrole Generation Using DDQ: A mixture
2-Methyl-5-propyl-1-tosyl-3-pyrroline (5): The reaction of 1i (70 mg,
0.31 mmol), CuBr (18 mg, 0.12 mmol), n-butylaldehyde (0.06 mL,
0.62 mmol), and di-n-butylamine (0.11 mL, 0.62 mmol) in dioxane
(2 mL) afforded 5 (59 mg, 68%) as a mixture of cis-5 and trans-5
(1.3:1), after column chromatography (hexane/EtOAc, 20:1). For
of pyrroline 3a (100 mg, 0.45 mmol) and DDQ (305 mg,
1.34 mmol) in benzene (4.5 mL) was heated at 110 °C under nitro-
gen for 5 h. The progress of the reaction was followed by TLC.
After the reaction was complete, the reaction mixture was concen-
trated under reduced pressure and the resulting residue purified by
column chromatography.
1
cis-5, H NMR (300 MHz, CDCl3): δ = 7.70 (d, J = 8.4 Hz, 2 H),
7.28 (d, J = 8.4 Hz, 2 H), 5.54–5.47 (m, 2 H), 4.42–4.34 (m, 2 H),
2.41 (s, 3 H), 1.86–1.74 (m, 1 H), 1.69–1.59 (m, 1 H), 1.48–1.26 (m,
2 H), 1.38 (d, J = 6.2 Hz, 3 H), 0.94 (t, J = 7.3 Hz, 3 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 143.2, 130.4, 129.6, 128.4, 127.5, 67.9,
63.6, 39.8, 23.7, 21.5, 18.4, 14.1 ppm. HRMS (EI): calcd. for
C15H21NO2S [M]+ 279.1293, found 279.1292. For (2R)-5, the reac-
tion of (R)-1i (45 mg, 0.20 mmol), CuBr (11 mg, 0.08 mmol), n-
butylaldehyde (0.04 mL, 0.40 mmol), and di-n-butylamine
(0.07 mL, 0.40 mmol) in dioxane (1.3 mL) afforded (2R)-5 (27 mg,
58%) as a mixture of cis-(2R,5S)-5 and trans-(2R,5R)-5 (1.1:1), af-
ter column chromatography (hexane/EtOAc, 20:1). (2R,5S)-5;
HPLC Chiral OJ-H column (99:1 hexanes/2-propanol, 1 mL/min)
tR 13.1 min (major), 16.3 min (minor): 99% ee. For (2R,5R)-5;
HPLC Chiral OJ-H column (99:1 hexanes/2-propanol, 1 mL/min)
tR 16.3 min (minor), 22.1 min (major): 98% ee.
Tosyl-1H-pyrrole (7a):[24] The reaction of 3a (100 mg, 0.45 mmol)
and DDQ (305 mg, 1.34 mmol) in benzene (4.5 mL) afforded 7a
(99 mg, 99%), after column chromatography (hexane/EtOAc, 10:1),
1
m.p. 99 °C. H NMR (300 MHz, CDCl3): δ = 7.74 (d, J = 8.4 Hz,
2 H), 7.28 (d, J = 8.3 Hz, 2 H), 7.15 (t, J = 2.2 Hz, 2 H), 6.28 (t,
J = 2.2 Hz, 2 H), 2.40 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 144.9, 130.0, 126.8, 120.7, 113.5, 21.6 ppm. HRMS (EI): calcd.
for C11H11NO2S [M]+ 221.0510, found 221.0504.
2-Methyl-1-tosyl-1H-pyrrole (7i):[15a] The reaction of 3i (52 mg,
0.22 mmol) and DDQ (150 mg, 0.66 mmol) in benzene (2.2 mL)
afforded 7i (26 mg, 50%), after column chromatography (hexane/
EtOAc, 10:1). 1H NMR (300 MHz, CDCl3): δ = 7.66 (d, J =
8.4 Hz, 2 H), 7.30–7.26 (m, 3 H), 6.15 (t, J = 3.7 Hz, 1 H), 5.94 (s,
1 H), 2.40 (s, 3 H), 2.29 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 144.7, 129.9, 126.8, 122.0, 113.0, 111.1, 21.6, 13.5 ppm. HRMS
(EI): calcd. for C12H13NO2S [M]+ 235.0667, found 235.0667.
2-Phenyl-5-propyl-1-tosyl-3-pyrroline (6a): The reaction of 1l
(50 mg, 0.18 mmol), CuBr (10 mg, 0.07 mmol), n-butylaldehyde
(0.03 mL, 0.35 mmol), and di-n-butylamine (0.06 mL, 0.35 mmol)
in dioxane (1.2 mL) afforded 6a (37 mg, 60%) as a mixture of cis-6a
and trans-6a (1.6:1), after column chromatography (hexane/EtOAc,
20:1). For cis-6a, 1H NMR (300 MHz, CDCl3): δ = 7.62 (d, J =
8.4 Hz, 2 H), 7.34 (d, J = 8.8 Hz, 2 H), 7.37–7.23 (m, 5 H), 5.75
(dq, J = 5.1, 1.3 Hz, 1 H), 5.62 (dq, J = 5.1, 1.3 Hz, 1 H), 5.46 (d,
J = 1.8 Hz, 1 H), 4.54–4.48 (m, 1 H), 2.40 (s, 3 H), 2.01–1.92 (m,
1 H), 1.67–1.58 (m, 1 H), 1.48–1.35 (m, 2 H), 0.95 (t, J = 7.3 Hz,
3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 143.3, 140.9, 135.2,
129.5, 129.1, 129.0, 128.4, 127.6, 127.1, 70.5, 68.0, 39.8, 21.5, 19.2,
14.1 ppm. HRMS (EI): calcd. for C20H23NO2S [M]+ 341.1449,
found 341.1447.
2-Isopropyl-1-tosyl-1H-pyrrole (7j):[25] The reaction of 3j (45 mg,
0.17 mmol) and DDQ (58 mg, 0.25 mmol) in benzene (1.7 mL) af-
forded 7j (25 mg, 57%), after column chromatography (hexane/
EtOAc, 10:1). 1H NMR (300 MHz, CDCl3): δ = 7.52 (d, J =
8.1 Hz, 2 H), 7.20–7.16 (m, 3 H), 6.14–6.12 (m, 1 H), 5.97–5.95 (m,
1 H), 3.26–3.15 (m, 1 H), 2.32 (s, 3 H), 1.04 (d, J = 7.4 Hz, 6
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 144.6, 143.0, 136.8,
129.9, 126.4, 122.2, 111.4, 109.8, 26.2, 23.8, 21.6 ppm. HRMS (EI):
calcd. for C14H17NO2S [M]+ 263.0980, found 263.0968.
2-(p-Tolyl)-1-tosyl-1H-pyrrole (7m):[16,26] The reaction of 3m
(46 mg, 0.15 mmol) and DDQ (100 mg, 0.44 mmol) in benzene
(1.5 mL) afforded 7m (32 mg, 68%), after column chromatography
1
2-Isopropyl-5-phenyl-1-tosyl-3-pyrroline (6b): The reaction of 1l
(50 mg, 0.18 mmol), CuBr (10 mg, 0.07 mmol), isobutyraldehyde
(0.03 mL, 0.36 mmol), and diisobutylamine (0.06 mL, 0.36 mmol)
in dioxane (1.2 mL) afforded 6b (24 mg, 40%) as a mixture of cis-6b
and trans-6b (3.3:1), after column chromatography (hexane/EtOAc,
20:1). For cis-6b, 1H NMR (300 MHz, CDCl3): δ = 7.63 (d, J =
8.4 Hz, 2 H), 7.44 (d, J = 7.0 Hz, 2 H), 7.36–7.24 (m, 5 H), 5.73
(hexane/EtOAc, 10:1), m.p. 107 °C. H NMR (300 MHz, CDCl3):
δ = 7.42–7.40 (m, 1 H), 7.26–7.24 (m, 3 H), 7.12–7.09 (m, 5 H),
6.30–6.28 (m, 1 H), 6.13–6.11 (m, 1 H), 2.40 (s, 3 H), 2.36 (s, 3
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 144.6, 138.1, 136.1,
135.7, 130.7, 129.3, 128.5, 128.1, 127.1, 123.9, 113.6, 112.1, 21.6,
21.3 ppm. HRMS (EI): calcd. for C18H17NO2S [M]+ 311.0980,
found 311.0981.
2310
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 2305–2311

3-Pyrroline Synthesis by Copper-Catalyzed Domino Reactions
[8] a) S.-K. Kang, K.-J. Kim, Org. Lett. 2001, 3, 511; b) S. Ma, F.
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2-(4-Bromophenyl)-1-tosyl-1H-pyrrole (7q): The reaction of 3q
(41 mg, 0.11 mmol) and DDQ (75 mg, 0.33 mmol) in benzene
(1.1 mL) afforded 7q (28 mg, 69%), after column chromatography
1
(hexane/EtOAc, 10:1), m.p. 114 °C. H NMR (300 MHz, CDCl3):
[10]
a) S. Searles, Y. Li, B. Nassim, M.-T. R. Lopes, P. T. Tran, P.
Crabbé, J. Chem. Soc. Perkin Trans. 1 1984, 747; b) J. Kuang,
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δ = 7.45–7.42 (m, 3 H), 7.26–7.24 (m, 2 H), 7.14–7.10 (m, 4 H),
6.31–6.29 (m, 1 H), 6.16–6.14 (m, 1 H), 2.36 (s, 3 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 144.8, 135.4, 134.7, 132.3, 130.5,
129.4, 127, 124.5, 122.6, 116.2, 112.2, 49.4, 21.6 ppm. HRMS (EI):
calcd. for C17H14BrNO2S [M]+ 374.9929, found 374.9924.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental details, characterization data, and copies of the
1H NMR and 13C NMR spectra of the products.
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amines were ineffective.
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Acknowledgments
This study was supported by a post-doctoral fellowship grant from
the Kyung Hee University in 2011 (KHU-20110218).
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Received: October 29, 2013
Published Online: February 13, 2014
Eur. J. Org. Chem. 2014, 2305–2311
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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