Expeditious synthesis of functionalized piperidines by regioselective ring opening of aziridines by enals catalyzed by an N-heterocyclic carbene

Article abstract of DOI:10.1055/s-0030-1258161

A novel, expeditious, and diastereoselective synthesis of 2,6-disubstituted piperidin-4-ones is reported. Regioselective ring opening catalyzed by an N-heterocyclic carbene (NHC) of terminal aziridines by enals affords β′-amino α,β-unsaturated ketones, which on intramolecular aza-Michael addition in the presence of potassium carbonate furnish 2,6-disubstituted piperidin-4-ones cis-selectively, in excellent yields (83-95%). The protocol involves carbonyl umpolung reactivity of enals, in which the carbonyl carbon nucleophilically attacks the electrophilic terminal aziridines. The absence of byproduct formation, operational simplicity, the use of ambient temperature, high yields, and regio- and diastereoselectivity are the salient features of this procedure.

Full text of DOI:10.1055/s-0030-1258161

PAPER
2957
Expeditious Synthesis of Functionalized Piperidines by Regioselective Ring
Opening of Aziridines by Enals Catalyzed by an N-Heterocyclic Carbene
Synthesis of
P
a
iperidin-4-o
n
nes from
A
z
t
iridinesosh Singh,a Vijai K. Rai,a,b Pankaj Singh,a Lal Dhar S. Yadav*a
a
Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211 002, India
Fax +91(532)2460533; E-mail: ldsyadav@hotmail.com
b
College of Science, Shri Mata Vaishno Devi University, Katra, Jammu & Kashmir 182 320, India
Received 19 April 2010; revised 28 April 2010
The inversion of standard functional group polarity, or
umpolung, is a powerful strategy in chemistry, and facili-
tates the construction of organic molecules in unusual
ways.10,11 Over the last decade, there has been a continu-
Abstract: A novel, expeditious, and diastereoselective synthesis of
2,6-disubstituted piperidin-4-ones is reported. Regioselective ring
opening catalyzed by an N-heterocyclic carbene (NHC) of terminal
aziridines by enals affords b¢-amino a,b-unsaturated ketones, which
on intramolecular aza-Michael addition in the presence of potassi- ously growing number of successful and novel applica-
um carbonate furnish 2,6-disubstituted piperidin-4-ones cis-selec-
tions of N-heterocyclic carbenes (NHCs) as
tively, in excellent yields (83–95%). The protocol involves
organocatalysts and reagents for an expanding set of reac-
carbonyl umpolung reactivity of enals, in which the carbonyl car-
tions.11 NHC-catalyzed umpolung reactivity of a,b- unsat-
bon nucleophilically attacks the electrophilic terminal aziridines.
urated aldehydes (enals) via the Breslow or homoenolate
The absence of byproduct formation, operational simplicity, the use
intermediate and its synthetic utilization has been well
documented,12–14 where addition of an appropriate NHC
to an enal renders it a d3 nucleophile. Stetter and cowork-
ers published as early as 1979 a few examples of the
Michael addition of enals as acyl anions.15 Since then,
there have been only two reports on NHC-catalyzed um-
polung reactivity of enals rendering them acyl anion
equivalents (d1 nucleophiles), although it would be of
considerable synthetic utility.16a,b
of ambient temperature, high yields, and regio- and diastereoselec-
tivity are the salient features of this procedure.
Key words: N-heterocyclic carbenes, aziridines, umpolung, enals,
aza-Michael addition, piperidines
The piperidine ring is an essential building block for nu-
merous bioactive alkaloids, natural products, and synthet-
ic pharmaceuticals.1 Several 2,6-disubstituted piperidine
derivatives have been found to possess useful biological
activities.2 The biological activities of piperidones were
found to be excellent if 2- and/or 6-positions are occupied
by aryl groups.2a,b,3 Accordingly, antibacterial and anti-
fungal activities of 2,6-diarylpiperidin-4-ones and their
derivatives have been well explored.2b,4 Modular con-
structions of functionalized piperidines such as substitut-
ed piperidin-4-ones are important synthetic targets
because these are intermediates for the preparation of var-
ious alkaloids and pharmaceuticals. Especially 2,6-disub-
stituted piperidin-4-ones are regarded as important
frameworks, and serve as precursors for chiral biological-
ly active natural alkaloids.1h,5 As a consequence, the de-
velopment of general methods for the synthesis of
piperidine derivatives has been the subject of considerable
synthetic effort and still requires attention.6 Moreover, b-
amino carbonyl compounds are ubiquitous in the natural
product arena and have been used as building blocks for
many N-containing biologically important compounds7
such as 1,2-diamines and b-lactams.8,9 We envisioned that
intramolecular aza-Michael addition of b¢-amino a,b- un-
saturated ketones would be an expeditious method for di-
rect access to the 2,6-disubstituted piperidine framework.
In view of filling this remarkable gap in the literature on
the synthetic utility of NHC-catalyzed acyl anion equiva-
lent reactivity of enals, and in continuation of our ongoing
efforts to develop synthetically useful processes,16 we re-
port herein a novel methodology developed for an effi-
cient construction of chemically and pharmaceutically
potent 2,6-disubstituted piperidin-4-ones 5. The protocol
involves intramolecular aza-Michael addition of b¢-amino
a,b-unsaturated ketones 4 generated by NHC-catalyzed
regioselective ring opening of terminal aziridines 2 by
enals 1 (Scheme 1). Recently, various NHC-catalyzed re-
Ph
Cl–
N+
N
Ts
N
O
3
DBU
Ph
+
Ar1
H
THF–t-BuOH, r.t.
80–94%
Ar2
1
2
O
N
O
NHTs
Ar2
K2CO3 (10 mol%)
Ar1
DMSO, 2–3 h
83–95%
Ar1
Ar2
4
Ts
5
SYNTHESIS 2010, No. 17, pp 2957–2964
x
x.
x
x
.
2
0
1
0
Advanced online publication: 07.07.2010
DOI: 10.1055/s-0030-1258161; Art ID: Z10010SS
Scheme 1 Synthesis of 2,6-disubstituted piperidin-4-ones 5
© Georg Thieme Verlag Stuttgart · New York

2958
S. Singh et al.
PAPER
gioselective ring-opening reactions of aziridines with al- basic alumina. The effect of the solvent on the formation
dehydes, acid anhydrides, and silylated nucleophiles have of 5a (Ar1 = Ar2 = Ph; Table 1) was also examined and it
been reported.17 Several examples of intramolecular cy- was noted that dimethyl sulfoxide was the best solvent in
clization by the aza-Michael reaction have also been re- terms of yield among the tested solvents tetrahydrofuran,
ported for the synthesis of substituted piperidines.18 dichloromethane, methanol, and dimethyl sulfoxide. The
Interestingly, in the present study the key intermediates reaction was performed at room temperature. On stirring
b¢-amino ketones 4 are obtained by the carbonyl umpol- ketone 4a (Ar1 = Ar2 = Ph) in dimethyl sulfoxide with
ung reaction of enals with terminal aziridines,16b which on five mol% of potassium carbonate at room temperature
further treatment with potassium carbonate afford 2,6-dis- for 15 hours, the corresponding piperidin-4-one 5a was
ubstituted piperidin-4-ones 5.
obtained only in moderate yield (51%). When the catalyst
loading was increased to ten mol%, we found that the re-
action conversion was completed within three hours to
give an excellent yield (91%) of 5a. However, on further
increasing the catalyst loading to 15 mol%, no improve-
ment in the yield was noticed. Therefore, ten mol% of po-
tassium carbonate in dimethyl sulfoxide was used for the
intramolecular aza-Michael addition step.
To begin with, the requisite b¢-amino ketones were conve-
niently prepared by recently reported NHC-catalyzed ring
opening of aziridines16b (Scheme 1). Then we optimized
the catalyst for the intramolecular aza-Michael addition,
and found that potassium carbonate was the best among
1,8-diazabicyclo[5.4.0]undec-7-ene,
lo[2.2.2]octane, potassium carbonate, triethylamine, and
1,4-diazabicyc-
Table 1 Intramolecular Aza-Michael Addition of b¢-Amino Ketones 4 Leading to 2,6-Disubstituted Piperidin-4-ones 5
O
O
NHTs
Ar2
K2CO3 (10 mol%)
DMSO, r.t.
Ar1
Ar1
N
Ar2
4
Ts
5
Entry
1
b¢-Amino ketone 4
Timea (h)
Piperidin-4-one 5
Yieldb,c (%)
O
O
NHTs
3
2
91
Ph
N
Ph
Ts
4a
5a
O
O
NHTs
2
3
4
91
88
90
N
Ph
MeO
Ts
MeO
4b
5b
O
O
NHTs
2
3
N
Ph
O2N
Ts
O2N
4c
5c
O
N
O
NHTs
Ph
Cl
Ts
Cl
4d
5d
Synthesis 2010, No. 17, 2957–2964 © Thieme Stuttgart · New York

PAPER
Synthesis of Piperidin-4-ones from Aziridines
2959
Table 1 Intramolecular Aza-Michael Addition of b¢-Amino Ketones 4 Leading to 2,6-Disubstituted Piperidin-4-ones 5 (continued)
O
O
NHTs
Ar2
K2CO3 (10 mol%)
DMSO, r.t.
Ar1
Ar1
N
Ar2
4
Ts
5
Entry
b¢-Amino ketone 4
Timea (h)
Piperidin-4-one 5
Yieldb,c (%)
O
O
NHTs
2
5
83
N
Ph
Ts
OMe
OMe
4e
5e
O
O
NHTs
Cl
6
7
3
3
92
88
Cl
Ph
N
Ts
4f
5f
O
O
NHTs
N
OMe
MeO
Ts
MeO
OMe
4g
5g
O
O
NHTs
8
9
2
2
95
94
N
OMe
O2N
Ts
O2N
OMe
4h
5h
O
O
NHTs
N
OMe
Cl
Ts
Cl
OMe
4i
5i
O
O
NHTs
10
11
2
3
90
93
N
OMe
Ts
OMe
OMe
OMe
4j
5j
O
O
NHTs
Cl
Cl
N
O2N
Ts
O2N
4k
5k
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S. Singh et al.
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Table 1 Intramolecular Aza-Michael Addition of b¢-Amino Ketones 4 Leading to 2,6-Disubstituted Piperidin-4-ones 5 (continued)
O
O
NHTs
Ar2
K2CO3 (10 mol%)
DMSO, r.t.
Ar1
Ar1
N
Ar2
4
Ts
5
Entry
12
b¢-Amino ketone 4
Timea (h)
Piperidin-4-one 5
Yieldb,c (%)
O
O
NHTs
Cl
2
2
2
93
Cl
N
MeO
Ts
MeO
4l
5l
O
O
NHTs
13
14
92
90
N
NO2
O2N
Ts
O2N
NO2
4m
5m
O
N
O
NHTs
NO2
Cl
Ts
Cl
NO2
4n
5n
O
O
NHTs
15
3
89
N
NO2
Ts
NO2
OMe
OMe
4o
5o
a Stirring time at r.t.
b Yield of isolated and purified product.
c All compounds gave satisfactory elemental analysis (C, H, and N; 0.38%) and spectral (IR, 1H NMR, 13C NMR, and EIMS) data.
Next, we probed the scope of this reaction by using the op- the existing procedures for the synthesis of this kind of
timized reaction conditions with a variety of intermediate fine chemicals.
ketones 4 (Table 1). We were successful at preparing a li-
brary of 15 piperidin-4-ones in excellent yields (83–95%),
with 5h obtained in the highest yield of 95% (Table 1, en-
try 8). It was gratifying to find that the formation of the
2,6-disubstituted piperidin-4-ones 5 was entirely diaste-
reoselective in favor of the cis isomer. The relative stereo-
chemistry of 5 was established by NOE experiments
(Figure 1). Strong NOE (5.6–6.1%) was observed be-
tween H-2 and H-6 of products 5, which conclusively
demonstrates their cis stereochemistry.
5.6–6.1%
NOE
H
O
H
Ar2
N-Ts
Ar1
5
Figure 1
Melting points were determined by the open glass capillary method
and are uncorrected. IR spectra of samples prepared in KBr were re-
corded on a Perkin-Elmer 993 IR spectrophotometer. 1H NMR (400
MHz) and 13C NMR (100 MHz) spectra were recorded on a Bruker
WM-40 C FT spectrometer, with TMS as internal reference. Mass
spectra were recorded on a JEOL D-300 mass spectrometer. Ele-
mental analyses were carried out in a Coleman automatic carbon,
In summary, we have developed a convenient and effi-
cient synthetic route to piperidin-4-ones from aziridines.
The protocol also fills a remarkable gap in the literature on
the synthetic utility of NHC-catalyzed acyl anion equiva-
lent reactivity of enals. The present atom-economic and
workable methodology would be a practical alternative to hydrogen, and nitrogen analyzer. All chemicals used were reagent
Synthesis 2010, No. 17, 2957–2964 © Thieme Stuttgart · New York

PAPER
Synthesis of Piperidin-4-ones from Aziridines
2961
grade and were used as received without further purification. Silica
gel-G was used for TLC.
Anal. Calcd for C24H22N2O5S: C, 63.98; H, 4.92; N, 6.22. Found: C,
64.33; H, 4.79; N, 6.39.
2,6-Disubstituted Piperidin-4-ones 5; General Procedure
A mixture of b¢-amino-a,b-unsaturated ketone 4 (0.5 mmol) and
K2CO3 (0.05 mmol) in DMSO (1 mL) was stirred at r.t. for 2–3 h.
After completion of the reaction as indicated by TLC, the reaction
mixture was diluted with EtOAc (3 mL) and washed with H2O
(3 × 5 mL). The volatiles were evaporated under reduced pressure
to leave a crude product, which was purified by flash column chro-
matography (silica gel, hexane–EtOAc, 10:1); this afforded analyt-
ically pure piperidinones 5.
2-(4-Chlorophenyl)-6-phenyl-1-tosylpiperidin-4-one (5d)
Colorless solid; yield: 0.197 g (90%); mp 139–141 °C.
IR (KBr): 3017 (C–Harom), 2923 (C–Haliphatic), 1708 (C=O), 1599,
1585, 1457 (C=Carom), 1322, 1156 (SO2) cm–1.
1H NMR (400 MHz, CDCl3): d = 2.37 (s, 3 H, Me), 2.09–2.95 (m,
4 H, 2 × CH2), 3.95 (dd, J = 12.5, 2.8 Hz, 1 H, H-6), 4.11 (dd,
J = 11.5, 3.9 Hz, 1 H, H-2), 6.96 (d, J = 8.5 Hz, 2 H, ArH, 4-
ClC6H4), 7.05–7.21 (m, 5 H, ArH, Ph), 7.25 (d, J = 8.5 Hz, 2 H,
ArH, 4-ClC6H4), 7.32 (d, J = 8.7 Hz, 2 H, ArH, 4-MeC6H4), 7.70 (d,
J = 8.7 Hz, 2 H, ArH, 4-MeC6H4).
2,6-Diphenyl-1-tosylpiperidin-4-one (5a)
13C NMR (100 MHz, CDCl3): d = 25.9 (Me), 44.8 (C-5), 46.9 (C-
3), 51.5 (C-6), 60.4 (C-2), 125.8, 126.5, 127.1, 127.7, 128.5, 129.2,
130.6, 132.1, 134.8, 135.7, 139.1, 139.9 (Ph, 4-MeC6H4, 4-ClC6H4),
205.5 (C=O).
Colorless solid; yield: 0.184 g (91%); mp 109–110 °C.
IR (KBr): 3021 (C–Harom), 2920 (C–Haliphatic), 1705 (C=O), 1605,
1581, 1455 (C=Carom), 1321, 1155 (SO2) cm–1.
1H NMR (400 MHz, CDCl3): d = 2.38 (s, 3 H, Me), 2.85–2.91 (m,
4 H, 2 × CH2), 4.24 (dd, J = 11.6, 3.8 Hz, 2 H, H-2, H-6), 7.07–7.27
(m, 10 H, ArH), 7.33 (d, J = 8.5 Hz, 2 H, ArH, 4-MeC6H4), 7.69 (d,
J = 8.5 Hz, 2 H, ArH, 4-MeC6H4).
MS (EI): m/z = 439 [M+], 441 [M+ + 2].
Anal. Calcd for C24H22ClNO3S: C, 65.52; H, 5.04; N, 3.18. Found:
C, 65.39; H, 5.31; N, 3.01.
13C NMR (100 MHz, CDCl3): d = 25.8 (Me), 44.2 (C-5), 45.1 (C-
3), 51.8 (C-6), 52.5 (C-2), 126.5, 127.2, 127.9, 128.6, 129.1, 129.7,
130.5, 131.2, 135.7, 136.5, 137.2, 139.3 (2 × Ph, 4-MeC6H4), 205.5
(C=O).
2-(3-Methoxyphenyl)-6-phenyl-1-tosylpiperidin-4-one (5e)
Colorless solid; yield: 0.180 g (83%); mp 151–153 °C.
IR (KBr): 3025 (C–Harom), 2931 (C–Haliphatic), 1703 (C=O), 1605,
1585, 1449 (C=Carom), 1321, 1151 (SO2) cm–1.
MS (EI): m/z = 405 [M+].
1H NMR (400 MHz, CDCl3): d = 2.39 (s, 3 H, Me), 2.80–2.89 (m,
4 H, 2 × CH2), 3.79 (s, 3 H, OMe), 3.99 (dd, 1 H, J = 12.5, 2.6 Hz,
H-6), 4.11 (dd, J = 11.5, 3.2 Hz, 1 H, H-2), 6.98–7.31 (m, 9 H, ArH,
Ph, 3-MeOC6H4), 7.31 (d, J = 8.5 Hz, 2 H, ArH, 4-MeC6H4), 7.72
(d, J = 8.5 Hz, 2 H, ArH, 4-MeC6H4).
Anal. Calcd for C24H23NO3S: C, 71.09; H, 5.72; N, 3.45. Found: C,
71.31; H, 5.91; N, 3.28.
2-(4-Methoxyphenyl)-6-phenyl-1-tosylpiperidin-4-one (5b)
Colorless solid; yield: 0.197 g (91%); mp 147–149 °C.
13C NMR (100 MHz, CDCl3): d = 25.5 (Me), 45.1 (C-5), 47.2 (C-
3), 52.0 (C-6), 55.3 (OMe), 59.3 (C-2), 117.3, 126.2, 126.9, 127.5,
128.4, 129.2, 129.9, 130.5, 131.2, 135.9, 137.5, 139.1, 140.4, 157.1
(Ph, 4-MeC6H4, 3-MeOC6H4), 206.2 (C=O).
IR (KBr): 3027 (C–Harom), 2928 (C–Haliphatic), 1695 (C=O), 1608,
1585, 1451 (C=Carom), 1325, 1159 (SO2) cm–1.
1H NMR (400 MHz, CDCl3): d = 2.41 (s, 3 H, Me), 2.81–2.92 (m,
4 H, 2 × CH2), 3.81 (s, 3 H, OMe), 3.98 (dd, J = 12.5, 2.8 Hz, 1 H,
H-6), 4.15 (dd, J = 11.5, 3.4 Hz, 1 H, H-2), 6.98 (d, J = 8.7 Hz, 2 H,
ArH, 4-MeOC6H4), 7.06–7.22 (m, 5 H, ArH, Ph), 7.26 (d, J = 8.7
Hz, 2 H, ArH, 4-MeOC6H4), 7.34 (d, J = 8.4 Hz, 2 H, ArH, 4-
MeC6H4), 7.71 (d, J = 8.4 Hz, 2 H, ArH, 4-MeC6H4).
MS (EI): m/z = 435 [M+].
Anal. Calcd for C25H25NO4S: C, 68.94; H, 5.79; N, 3.22. Found: C,
69.13; H, 5.65; N, 3.57.
13C NMR (100 MHz, CDCl3): d = 25.5 (Me), 44.7 (C-5), 46.5 (C-
3), 51.2 (C-6), 53.9 (OMe), 58.7 (C-2), 121.2, 126.6, 127.3, 127.9,
128.5, 129.3, 130.0, 130.8, 135.5, 139.1, 140.1, 156.5 (Ph, 4-
MeC6H4, 4-MeOC6H4), 205.5 (C=O).
2-(3-Chlorophenyl)-6-phenyl-1-tosylpiperidin-4-one (5f)
Colorless solid; yield: 0.201 g (92%); mp 103–105 °C.
IR (KBr): 3019 (C–Harom), 2928 (C–Haliphatic), 1702 (C=O), 1608,
1581, 1455 (C=Carom), 1320, 1155 (SO2) cm–1.
MS (EI): m/z = 435 [M+].
1H NMR (400 MHz, CDCl3): d = 2.43 (s, 3 H, Me), 2.81–2.94 (m,
4 H, 2 × CH2), 4.01 (dd, J = 12.4, 2.8 Hz, 1 H, H-6), 4.23 (dd,
J = 11.9, 3.5 Hz, 1 H, H-2), 7.01–7.31 (m, 9 H, ArH, Ph, 3-ClC6H4),
7.34 (d, J = 8.4 Hz, 2 H, ArH, 4-MeC6H4), 7.74 (d, J = 8.4 Hz, 2 H,
ArH, 4-MeC6H4).
Anal. Calcd for C25H25NO4S: C, 68.94; H, 5.79; N, 3.22. Found: C,
68.59; H, 5.58; N, 3.13.
2-(4-Nitrophenyl)-6-phenyl-1-tosylpiperidin-4-one (5c)
13C NMR (100 MHz, CDCl3): d = 25.3 (Me), 44.5 (C-5), 46.5 (C-
3), 51.6 (C-6), 58.8 (C-2), 121.2, 124.8, 125.9, 126.5, 127.1, 128.5,
129.4, 130.2, 131.3, 135.7, 136.4, 138.1, 139.2, 140.4 (Ph, 4-
MeC6H4, 3-ClC6H4), 206.8 (C=O).
Colorless solid; yield: 0.198 g (88%); mp 160–162 °C.
IR (KBr): 3022 (C–Harom), 2921 (C–Haliphatic), 1706 (C=O), 1603,
1579, 1458 (C=Carom), 1320, 1153 (SO2) cm–1.
1H NMR (400 MHz, CDCl3): d = 2.40 (s, 3 H, Me), 2.88–2.91 (m,
4 H, 2 × CH2), 4.02 (dd, J = 12.0, 2.6 Hz, 1 H, H-6), 4.19 (dd,
J = 11.3, 3.9 Hz, 1 H, H-2), 7.03–7.27 (m, 5 H, ArH, Ph), 7.35 (d,
J = 8.5 Hz, 2 H, ArH, 4-MeC6H4), 7.61 (d, J = 8.7 Hz, 2 H, ArH, 4-
O2NC6H4), 7.71 (d, J = 8.5 Hz, 2 H, ArH, 4-MeC6H4), 8.19 (d,
J = 8.7 Hz, 2 H, ArH, 4-O2NC6H4).
MS (EI): m/z = 439 [M+].
Anal. Calcd for C24H22ClNO3S: C, 65.52; H, 5.04; N, 3.18. Found:
C, 65.19; H, 5.28; N, 3.39.
2,6-Bis(4-methoxyphenyl)-1-tosylpiperidin-4-one (5g)
13C NMR (100 MHz, CDCl3): d = 25.3 (Me), 44.5 (C-5), 48.3 (C-
3), 51.5 (C-6), 58.9 (C-2), 126.2, 126.8, 127.4, 128.1, 128.8, 129.4,
130.5, 131.2, 135.5, 139.1, 140.8, 145.2 (Ph, 4-MeC6H4, 4-
O2NC6H4), 205.9 (C=O).
Colorless solid; yield: 0.204 g (88%); mp 119–121 °C.
IR (KBr): 3011 (C–Harom), 2925 (C–Haliphatic), 1699 (C=O), 1603,
1585, 1459 (C=Carom), 1326, 1154 (SO2) cm–1.
1H NMR (400 MHz, CDCl3): d = 2.40 (s, 3 H, Me), 2.79–2.90 (m,
4 H, 2 × CH2), 3.81 (s, 3 H, OMe), 3.85 (s, 3 H, OMe), 4.19 (dd,
MS (EI): m/z = 450 [M+].
Synthesis 2010, No. 17, 2957–2964 © Thieme Stuttgart · New York

2962
S. Singh et al.
PAPER
J = 11.2, 3.5 Hz, 2 H, H-2, H-6), 7.02 (d, J = 8.6 Hz, 4 H, ArH,
2 × 4-MeOC6H4), 7.21 (d, J = 8.6 Hz, 4 H, ArH, 2 × 4-MeOC6H4),
7.33 (d, J = 8.5 Hz, 2 H, ArH, 4-MeC6H4), 7.72 (d, J = 8.5 Hz, 2 H,
ArH, 4-MeC6H4).
7.31 (d, J = 8.5 Hz, 2 H, ArH, 4-MeC6H4), 7.69 (d, J = 8.5 Hz, 2 H,
ArH, 4-MeC6H4).
13C NMR (100 MHz, CDCl3): d = 25.7 (Me), 45.0 (C-5), 46.6 (C-
3), 51.7 (C-6), 54.1 (OMe), 54.9 (OMe), 60.3 (C-2), 115.8, 117.7,
118.9, 126.5, 127.3, 127.9, 128.6, 129.7, 130.4, 135.9, 138.3, 140.5,
155.1, 156.8 (4-MeOC6H4, 3-MeOC6H4, 4-MeC6H4), 207.5 (C=O).
13C NMR (100 MHz, CDCl3): d = 26.1 (Me), 44.7 (C-5), 45.5 (C-
6), 46.6 (C-3), 54.2 (OMe), 55.0 (OMe), 58.9 (C-2), 117.3, 118.5,
126.2, 127.1, 128.6, 129.4, 131.2, 135.6, 140.3, 130.5, 156.3, 157.1
(4-MeC6H4, 2 × 4-MeOC6H4), 207.7 (C=O).
MS (EI): m/z = 465 [M+].
Anal. Calcd for C26H27NO5S: C, 67.08; H, 5.85; N, 3.01. Found: C,
66.91; H, 5.63; N, 3.36.
MS (EI): m/z = 465 [M+].
Anal. Calcd for C26H27NO5S: C, 67.08; H, 5.85; N, 3.01. Found: C,
66.79; H, 5.96; N, 2.88.
2-(3-Chlorophenyl)-6-(4-nitrophenyl)-1-tosylpiperidin-4-one
(5k)
2-(4-Methoxyphenyl)-6-(4-nitrophenyl)-1-tosylpiperidin-4-one
(5h)
Colorless solid; yield: 0.228 g (95%); mp 143–145 °C.
Colorless solid; yield: 0.225 g (93%); mp 125–127 °C.
IR (KBr): 3021 (C–Harom), 2928 (C–Haliphatic), 1703 (C=O), 1598,
1581, 1451 (C=Carom), 1325, 1151 (SO2) cm–1.
IR (KBr): 3021 (C–Harom), 2920 (C–Haliphatic), 1705 (C=O), 1608,
1587, 1456 (C=Carom), 1319, 1152 (SO2) cm–1.
1H NMR (400 MHz; CDCl3): d = 2.35 (s, 3 H, Me), 2.80–2.97 (m,
4 H, 2 × CH2), 4.07 (dd, J = 12.4, 2.5 Hz, 1 H, H-6), 4.25 (dd,
J = 11.6, 3.8 Hz, 1 H, H-2), 7.03–7.26 (m, 4 H, ArH, 3-ClC6H4),
7.33 (d, J = 8.5 Hz, 2 H, ArH, 4-MeC6H4), 7.58 (d, J = 8.8 Hz, 2 H,
ArH, 4-O2NC6H4), 7.72 (d, J = 8.5 Hz, 2 H, ArH, 4-MeC6H4), 8.18
(d, J = 8.8 Hz, 2 H, ArH, 4-O2NC6H4).
13C NMR (100 MHz, CDCl3): d = 25.5 (Me), 45.8 (C-5), 47.5 (C-
3), 52.5 (C-6), 60.1 (C-2), 122.5, 126.2, 127.5 128.1, 128.8, 129.7,
130.6, 131.4 133.6, 135.6, 136.4, 140.9, 143.5, 145.2 (3-ClC6H4, 4-
O2NC6H4, 4-MeC6H4), 205.4 (C=O).
1H NMR (400 MHz, CDCl3): d = 2.38 (s, 3 H, Me), 2.68–2.92 (m,
4 H, 2 × CH2), 3.78 (s, 3 H, OMe), 3.93 (dd, J = 12.3, 2.9 Hz, 1 H,
H-6), 4.21 (dd, J = 11.4, 3.8 Hz, 1 H, H-2), 7.04 (d, J = 8.7 Hz, 2 H,
ArH, 4-MeOC6H4), 7.23 (d, J = 8.7 Hz, 2 H, ArH, 4-MeOC6H4),
7.32 (d, J = 8.6 Hz, 2 H, ArH, 4-MeC6H4), 7.59 (d, J = 8.9 Hz, 2 H,
ArH, 4-O2NC6H4), 7.74 (d, J = 8.6 Hz, 2 H, ArH, 4-MeC6H4), 8.20
(d, J = 8.9 Hz, 2 H, ArH, 4-O2NC6H4).
13C NMR (100 MHz, CDCl3): d = 25.8 (Me), 45.5 (C-5), 46.9 (C-
3), 52.8 (C-6), 54.9 (OMe), 60.3 (C-2), 118.2, 125.6, 126.4, 127.1,
128.7, 129.4, 130.3, 135.7, 140.5, 143.6, 145.5, 155.5 (4-MeC6H4,
4-MeOC6H4, 4-O2NC6H4), 207.1 (C=O).
MS (EI): m/z = 484 [M+].
Anal. Calcd for C24H21ClN2O5S: C, 59.44; H, 4.36; N, 5.78. Found:
C, 59.78; H, 4.53; N, 5.59.
MS (EI): m/z = 480 [M+].
Anal. Calcd for C25H24N2O6S: C, 62.49; H, 5.03; N, 5.83. Found: C,
62.31; H, 4.31; N, 5.59.
2-(3-Chlorophenyl)-6-(4-methoxyphenyl)-1-tosylpiperidin-4-
one (5l)
Colorless solid; yield: 0.218 g (93%); mp 122–124 °C.
2-(4-Chlorophenyl)-6-(4-methoxyphenyl)-1-tosylpiperidin-4-
one (5i)
Colorless solid; yield: 0.220 g (94%); mp 136–138 °C.
IR (KBr): 3019 (C–Harom), 2921 (C–Haliphatic), 1702 (C=O), 1601,
1589, 1455 (C=Carom), 1324, 1151 (SO2) cm–1.
1H NMR (400 MHz, CDCl3): d = 2.39 (s, 3 H, Me), 2.79–2.94 (m,
4 H, 2 × CH2), 3.85 (s, 3 H, OMe), 3.95 (dd, J = 12.8, 2.9 Hz, 1 H,
H-6), 4.19 (dd, J = 11.5, 3.6 Hz, 1 H, H-2), 6.98 (d, J = 8.7 Hz, 2 H,
ArH, 4-MeOC6H4), 7.02–7.21 (m, 4 H, ArH, 3-ClC6H4), 7.25 (d,
J = 8.7 Hz, 2 H, ArH, 4-MeOC6H4), 7.32 (d, J = 8.5 Hz, 2 H, ArH,
4-MeC6H4), 7.68 (d, J = 8.5 Hz, 2 H, ArH, 4-MeC6H4).
13C NMR (100 MHz, CDCl3): d = 25.4 (Me), 44.5 (C-5), 47.2 (C-
3), 51.2 (C-6), 54.3 (OMe), 60.8 (C-2), 117.2, 124.9, 125.6, 126.4,
127.2, 127.9, 128.8, 129.9, 130.7, 131.5, 135.5, 138.7, 140.2, 155.4
(4-MeOC6H4, 3-ClC6H4, 4-MeC6H4), 207.1 (C=O).
IR (KBr): 3023 (C–Harom), 2919 (C–Haliphatic), 1705 (C=O), 1605,
1585, 1455 (C=Carom), 1322, 1157 (SO2) cm–1.
1H NMR (400 MHz, CDCl3): d = 2.42 (s, 3 H, Me), 2.79–2.90 (m,
4 H, 2 × CH2), 3.80 (s, 3 H, OMe), 3.96 (dd, J = 12.5, 2.6 Hz, 1 H,
H-6), 4.18 (dd, J = 11.7, 3.9 Hz, 1 H, H-2), 6.95 (d, J = 8.8 Hz, 2 H,
ArH, 4-ClC6H4), 7.02 (d, J = 8.7 Hz, 2 H, ArH, 4-MeOC6H4), 7.21
(d, J = 8.7 Hz, 2 H, ArH, 4-MeOC6H4), 7.25 (d, J = 8.8 Hz, 2 H,
ArH, 4-ClC6H4), 7.36 (d, J = 8.5 Hz, 2 H, ArH, 4-MeC6H4), 7.71 (d,
J = 8.5 Hz, 2 H, ArH, 4-MeC6H4).
13C NMR (100 MHz, CDCl3): d = 26.0 (Me), 45.3 (C-5), 47.8 (C-
3), 51.3 (C-6), 54.5 (OMe), 59.1 (C-2), 117.8, 126.5, 127.2, 127.9,
130.5, 131.1, 131.9, 132.9, 135.1, 136.4, 139.7, 156.2 (4-MeC6H4,
4-MeOC6H4, 4-ClC6H4), 205.9 (C=O).
MS (EI): m/z = 469 [M+].
Anal. Calcd for C25H24ClNO4S: C, 63.89; H, 5.51; N, 2.98. Found:
C, 63.13; H, 5.21; N, 3.19.
MS (EI): m/z = 469 [M+], 471 [M+ + 2].
2,6-Bis(4-nitrophenyl)-1-tosylpiperidin-4-one (5m)
Anal. Calcd for C25H24ClNO4S: C, 63.89; H, 5.15; N, 2.98. Found:
C, 63.61; H, 5.01; N, 3.36.
Colorless solid; yield: 0.227 g (92%); mp 123–125 °C.
IR (KBr): 3021 (C–Harom), 2925 (C–Haliphatic), 1706 (C=O), 1605,
1585, 1459 (C=Carom), 1322, 1157 (SO2) cm–1.
2-(3-Methoxyphenyl)-6-(4-methoxyphenyl)-1-tosylpiperidin-4-
one (5j)
Colorless solid; yield: 0.209 g (90%); mp 149–151 °C.
1H NMR (400 MHz, CDCl3): d = 2.44 (s, 3 H, Me), 2.82–2.93 (m,
4 H, 2 × CH2), 4.27 (dd, J = 11.5, 3.8 Hz, 2 H, H-2, H-6), 7.32 (d,
J = 8.7 Hz, 2 H, ArH, 4-MeC6H4), 7.56 (d, J = 8.8 Hz, 4 H, ArH,
2 × 4-O2NC6H4), 7.71 (d, J = 8.7 Hz, 2 H, ArH, 4-MeC6H4), 8.21 (d,
J = 8.8 Hz, 4 H, ArH, 2 × 4-O2NC6H4).
13C NMR (100 MHz, CDCl3): d = 26.2 (Me), 44.3 (C-5), 45.0 (C-
6), 47.3 (C-3), 58.7 (C-2), 121.7, 122.3, 127.9, 128.6, 129.3, 130.5,
135.7, 139.8, 143.1, 143.9, 144.7, 145.8 (2 × 4-O2NC6H4, 4-
MeC6H4), 206.2 (C=O).
IR (KBr): 3025 (C–Harom), 2923 (C–Haliphatic), 1707 (C=O), 1603,
1588, 1452 (C=Carom), 1321, 1155 (SO2) cm–1.
1H NMR (400 MHz, CDCl3): d = 2.41 (s, 3 H, Me), 2.81–2.95 (m,
4 H, 2 × CH2), 3.79 (s, 3 H, OMe), 3.91 (s, 3 H, OMe), 4.03 (dd,
J = 12.5, 2.3 Hz, 1 H, H-6), 4.27 (dd, J = 11.5, 3.4 Hz, 1 H, H-2),
6.97 (d, J = 8.7 Hz, 2 H, ArH, 4-MeOC6H4), 7.02–7.21 (m, 4 H,
ArH, 3-MeOC6H4), 7.24 (d, J = 8.7 Hz, 2 H, ArH, 4-MeOC6H4),
Synthesis 2010, No. 17, 2957–2964 © Thieme Stuttgart · New York

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Synthesis of Piperidin-4-ones from Aziridines
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MS (EI): m/z = 495 [M+].
3679. (j) Michael, J. P. Nat. Prod. Rep. 2008, 25, 139; and
references cited therein.
Anal. Calcd for C24H21N3O7S: C, 58.17; H, 4.27; N, 8.48. Found: C,
57.79; H, 4.11; N, 8.72.
(2) (a) Ganellin, C. R.; Spickett, R. G. W. J. Med. Chem. 1965,
8, 619. (b) IsKarev, N. A.; Shadurshkii, K. S. Farmakol.
Toksikol. 1965, 28, 184. (c) Walter, S.; Kinnard, B.;
William, J.; Joseph, B. P. J. Pharm. Sci. 1965, 54, 1025.
(d) Georgiev, V.; Petkova, B. Acta Physiol. Pharmacol.
Bulg. 1974, 2, 76. (e) Vankov, S.; Nachnoizsled, J. Khim.
Farm. Inst. 1974, 9, 231. (f) Ileana, B.; Dobre, V.; Duaz, N.
J. J. Prakt. Chem. 1985, 327, 667. (g) Mobia, I. G.;
Soldatendkov, A. T.; Fedorov, V. O.; Ageev, E. A.;
Sergeeva, N. D.; Lin, S.; Stashenko, E. E.; Prostakov, N. S.;
Andreeva, E. I. Khim. Farm. Zh. 1989, 23, 421.
(3) Perumal, R. V.; Adiraj, M.; Shanmugapandiyan, P. Indian
Drugs 2001, 38, 156.
(4) (a) Srinivasan, M.; Perumal, S.; Selvaraj, S. Chem. Pharm.
Bull. 2006, 54, 795. (b) Rameshkumar, N.; Veena, A.;
Ilavarasan, R.; Adiraj, M.; Shanmugapandiyan, P.; Sridhar,
S. K. Biol. Pharm. Bull. 2003, 26, 188.
(5) (a) Numata, A.; Ibuka, T. In The Alkaloids, Vol. 31; Brossi,
A., Ed.; Academic Press: New York, 1987, 193.
(b) Edwards, M. W.; Daly, J. W.; Myers, C. W. J. Nat. Prod.
1988, 51, 1188. (c) Grishina, G. V.; Gaidorova, E. L.;
Zefirov, N. S. Chem. Heterocycl. Compd. 1994, 30, 1401.
(d) Wang, C.-L.; Wuorola, M. A. Org. Prep. Proced. Int.
1992, 24, 585.
2-(4-Chlorophenyl)-6-(4-nitrophenyl)-1-tosylpiperidin-4-one
(5n)
Colorless solid; yield: 0.217 g (90%); mp 155–157 °C.
IR (KBr): 3025 (C–Harom), 2932 (C–Haliphatic), 1706 (C=O), 1608,
1588, 1450 (C=Carom), 1321, 1152 (SO2) cm–1.
1H NMR (400 MHz, CDCl3): d = 2.41 (s, 3 H, Me), 2.70–2.88 (m,
4 H, 2 × CH2), 3.99 (dd, J = 12.5, 2.6 Hz, 1 H, H-6), 4.25 (dd,
J = 11.7, 3.5 Hz, 1 H, H-2), 7.03 (d, J = 8.7 Hz, 2 H, ArH, 4-
ClC6H4), 7.23 (d, J = 8.7 Hz, 2 H, ArH, 4-ClC6H4), 7.34 (d, J = 8.5
Hz, 2 H, ArH, 4-MeC6H4), 7.58 (d, J = 8.8 Hz, 2 H, ArH, 4-
O2NC6H4), 7.68 (d, J = 8.5 Hz, 2 H, ArH, 4-MeC6H4), 8.18 (d
J = 8.8 Hz, 2 H, ArH, 4-O2NC6H4).
13C NMR (100 MHz, CDCl3): d = 26.1 (Me), 45.2 (C-5), 46.8 (C-
3), 52.5 (C-6), 60.4 (C-2), 122.2, 126.8, 128.5, 129.1, 130.8, 131.5,
133.5, 135.8, 136.5, 140.1, 143.4, 146.2 (4-ClC6H4, 4-O2NC6H4, 4-
MeC6H4), 205.9 (C=O).
MS (EI): m/z = 484 [M+], 486 [M+ + 2].
Anal. Calcd for C24H21ClN2O3S: C, 59.44; H, 4.36; N, 5.78. Found:
C, 59.71; H, 4.22; N, 5.56.
(6) (a) Kuethe, J. T.; Comins, D. L. Org. Lett. 1999, 1, 1031.
(b) Souers, A. J.; Ellman, J. A. J. Org. Chem. 2000, 65,
1222. (c) Amat, M.; Perez, M.; Llor, N.; Bosch, J.; Lago, E.;
Molins, E. Org. Lett. 2001, 3, 611. (d) Harris, J. M.; Padwa,
A. Org. Lett. 2002, 4, 2029. (e) Hu, X. E.; Kim, N. K.;
Ledoussal, B. Org. Lett. 2002, 4, 4499. (f) Shu, C.;
Liebeskind, L. S. J. Am. Chem. Soc. 2003, 125, 2878.
(g) Legault, C.; Charette, A. B. J. Am. Chem. Soc. 2003, 125,
6360. (h) Bahia, P. S.; Snaith, J. S. J. Org. Chem. 2004, 69,
3226. (i) Kim, C.; Bae, H. J.; Lee, J. H.; Jeong, W.; Kim, H.;
Sampath, V.; Rhee, Y. H. J. Am. Chem. Soc. 2009, 131,
14660. (j) Cui, L.; Peng, Y.; Zhang, L. J. Am. Chem. Soc.
2009, 131, 8394.
(7) (a) Misra, M.; Luthra, R.; Singh, K. L.; Sushil, K.
Comprehensive Natural Products Chemistry, Vol. 4; Barton,
D. H. R.; Nakanishi, K.; Meth-Cohn, O., Eds.; Pergamon:
Oxford, 1999, 25. (b) Enantioselective Synthesis of b-Amino
Acids; Juaristi, E., Ed.; Wiley-VCH: Weinheim, 1997.
(c) Liu, M.; Sibi, M. P. Tetrahedron 2002, 58, 7991.
(d) Cardillo, G.; Tomasini, C. Chem. Soc. Rev. 1996, 25,
117.
2-(3-Methoxyphenyl)-6-(4-nitrophenyl)-1-tosylpiperidin-4-one
(5o)
Colorless solid; yield: 0.213 g (89%); mp 131–133 °C.
IR (KBr): 3022 (C–Harom), 2941 (C–Haliphatic), 1705 (C=O), 1603,
1585, 1455 (C=Carom), 1323, 1155 (SO2) cm–1.
1H NMR (400 MHz, CDCl3): d = 2.39 (s, 3 H, Me), 2.81–2.90 (m,
4 H, 2 × CH2), 3.81 (s, 3 H, OMe), 4.01 (dd, J = 12.3, 2.8 Hz, 1 H,
H-6), 4.22 (dd, J = 11.5, 3.9 Hz, 1 H, H-2), 6.98–7.26 (m, 4 H, ArH,
3-MeOC6H4), 7.31 (d, J = 8.5 Hz, 2 H, ArH, 4-MeC6H4), 7.56 (d,
J = 8.8 Hz, 2 H, ArH, 4-O2NC6H4), 7.71 (d, J = 8.5 Hz, 2 H, ArH,
4-MeC6H4), 8.17 (d, J = 8.8 Hz, 2 H, ArH, 4-O2NC6H4).
13C NMR (100 MHz, CDCl3): d = 25.9 (Me), 45.8 (C-5), 47.1 (C-
3), 51.9 (C-6), 55.2 (OMe), 59.8 (C-2), 118.5, 122.2, 125.9, 126.5,
127.3, 128.7, 129.6, 130.8, 135.1, 149.8, 140.7, 143.9, 145.5, 156.8
(3-MeOC6H4, 4-O2NC6H4, 4-MeC6H4), 207.3 (C=O).
MS (EI): m/z = 480 [M+].
Anal. Calcd for C25H24N2O6S: C, 62.49; H, 5.03; N, 5.83. Found: C,
62.71; H, 4.88; N, 5.69.
(8) (a) Kleinmann, E. F. Comprehensive Organic Synthesis,
Vol. 2; Trost, B. M., Ed.; Pergamon: New York, 1991, 893.
(b) The Organic Chemistry of b-Lactams; Georg, G. I., Ed.;
VCH: Weinheim, 1993.
(9) (a) Abele, S.; Seebach, D. Eur. J. Org. Chem. 2000, 1.
(b) Sewald, N. Amino Acids 1996, 11, 397.
(10) (a) Seebach, D. Angew. Chem. Int. Ed. 1979, 18, 239.
(b) Enders, D.; Balensiefer, T. Acc. Chem. Res. 2004, 37,
534.
(11) (a) Maki, B. E.; Chan, A.; Scheidt, K. A. Synthesis 2008,
1306. (b) Enders, D.; Niemeier, O.; Henseler, A. Chem. Rev.
2007, 107, 5606. (c) Marion, N.; Díez-González, S.; Nolan,
I. P. Angew. Chem. Int. Ed. 2007, 46, 2988. (d) Zeitler, K.
Angew. Chem. Int. Ed. 2005, 44, 7506. (e) Johnson, J. S.
Angew. Chem. Int. Ed. 2004, 43, 1326.
Acknowledgment
We sincerely thank SAIF, Punjab University, Chandigarh, for pro-
viding microanalyses and spectra. S.S. and P.S. are grateful to the
CSIR, New Delhi, for the award of a Junior Research Fellowship
(JRF).
References
(1) (a) Baliah, V. Chem. Rev. 1983, 83, 379. (b) Findlay, J. A.
In The Alkaloids, Vol. 26; Brossi, A., Ed.; Academic Press:
London, 1985, 89. (c) Pinder, A. R. Nat. Prod. Rep. 1986, 3,
171. (d) Pinder, A. R. Nat. Prod. Rep. 1987, 4, 527.
(e) Pinder, A. R. Nat. Prod. Rep. 1989, 6, 67. (f) Pinder, A.
R. Nat. Prod. Rep. 1990, 7, 447. (g) Pinder, A. R. Nat. Prod.
Rep. 1992, 9, 491. (h) Angle, S. R.; Breitenbucher, J. G. In
Natural Products Chemistry: Stereoselective Synthesis, Part
J; Rahman, A. R., Ed.; Elsevier: New York, 1995, 453.
(i) Watson, P. S.; Jiang, B.; Scott, B. Org. Lett. 2000, 2,
(12) Sohn, S. S.; Rosen, E. L.; Bode, J. W. J. Am. Chem. Soc.
2004, 126, 14370.
(13) Burstein, C.; Glorius, F. Angew. Chem. Int. Ed. 2004, 43,
6205.
Synthesis 2010, No. 17, 2957–2964 © Thieme Stuttgart · New York

2964
S. Singh et al.
PAPER
(14) (a) Chan, A.; Scheidt, K. A. Org. Lett. 2005, 7, 905. (b) He,
M.; Bode, J. W. Org. Lett. 2005, 7, 3131. (c) He, M.;
Struble, J. R.; Bode, J. W. J. Am. Chem. Soc. 2006, 128,
8418. (d) Nair, V.; Vellalath, S.; Poonoth, M.; Suresh, E.
J. Am. Chem. Soc. 2006, 128, 8736. (e) Burstein, C.;
Tschan, S.; Xie, X.; Glorius, F. Synthesis 2006, 2418.
(f) Chiang, P.-C.; Kaeobamrung, J.; Bode, J. W. J. Am.
Chem. Soc. 2007, 129, 3520. (g) Chan, A.; Scheidt, K. A.
J. Am. Chem. Soc. 2008, 130, 2740.
(15) Stetter, H.; Hilboll, G.; Kuhlmann, H. Chem. Ber. 1979, 112,
84.
(16) (a) Yadav, L. D. S.; Singh, S.; Rai, V. K. Synlett 2010, 240.
(b) Yadav, L. D. S.; Rai, V. K.; Singh, S.; Singh, P.
Tetrahedron Lett. 2010, 51, 1657. (c) Yadav, L. D. S.; Rai,
V. K.; Singh, S. Synlett 2009, 1423. (d) Yadav, L. D. S.;
Singh, S.; Rai, V. K. Green Chem. 2009, 11, 878.
(e) Yadav, L. D. S.; Yadav, S.; Rai, A.; Rai, V. K.; Awasthi,
C. Tetrahedron 2008, 64, 1420. (f) Yadav, L. D. S.; Rai, V.
K. Tetrahedron Lett. 2008, 49, 5553. (g) Yadav, L. D. S.;
Rai, V. K. Synlett 2007, 1227. (h) Yadav, L. D. S.; Rai, V.
K. Tetrahedron Lett. 2006, 47, 395.
(17) (a) Liu, Y.-K.; Li, R.; Yue, L.; Li, B.-J.; Chen, Y.-C.; Wu,
Y.; Ding, L.-S. Org. Lett. 2006, 8, 1521. (b) Sun, X.; Ye, S.;
Wu, J. Eur. J. Org. Chem. 2006, 4787. (c) Wu, J.; Sun, X.;
Ye, S.; Sun, W. Tetrahedron Lett. 2006, 47, 4813.
(18) (a) Chandrasekhar, S.; Babu, G. S. K.; Reddy, Ch. R.
Tetrahedron: Asymmetry 2009, 20, 2216. (b) Chen, L.-J.;
Hou, D.-R. Tetrahedron: Asymmetry 2008, 19, 715.
(c) Davis, F. A.; Xu, H.; Zhang, J. J. Org. Chem. 2007, 72,
2046. (d) Fustero, S.; Jimenez, D.; Moscardo, J.; Catalan, S.;
Pozo, C. D. Org. Lett. 2007, 9, 5283.
Synthesis 2010, No. 17, 2957–2964 © Thieme Stuttgart · New York