Regioselective synthesis of 3-heteroarylpiperidin-2-ones and diazacyclopenta[a]phenalenone via carbenoid reactions

Article abstract of DOI:10.1016/j.tet.2008.12.070

Rhodium(II) catalyzed carbenoid reactions of 3-diazopiperidin-2-ones were carried out with indoles and pyrroles to afford the respective (3-indol-3-yl)- and (3-pyrrol-2-yl)piperidones with regioselectivity. Interestingly, the reaction of bis-diazoimide in

Full text of DOI:10.1016/j.tet.2008.12.070

Tetrahedron 65 (2009) 1567–1573
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Tetrahedron
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Regioselective synthesis of 3-heteroarylpiperidin-2-ones and
diazacyclopenta[a]phenalenone via carbenoid reactions
*
Sengodagounder Muthusamy , Pandurangan Srinivasan
School of Chemistry, Bharathidasan University, Tiruchirappalli 620 024, Tamil Nadu, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 25 October 2008
Received in revised form 22 December 2008
Accepted 23 December 2008
Available online 27 December 2008
Rhodium(II) catalyzed carbenoid reactions of 3-diazopiperidin-2-ones were carried out with indoles and
pyrroles to afford the respective (3-indol-3-yl)- and (3-pyrrol-2-yl)piperidones with regioselectivity.
Interestingly, the reaction of bis-diazoimide in the presence of Rh2(OAc)4 catalyst furnished di-
azacyclopenta[a]phenalenone in a tandem manner.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Diazocarbonyl compounds
Diazoimides
3-Heteroarylpiperidin-2-ones
Indoles
Pyrroles
Rhodium(II) acetate
1. Introduction
intermolecular carbenoid reactions of various N-alkylated 3-diazo-
piperidin-2-ones.
Diazocarbonyl compounds have been used for important
structural and functional group transformations in various reports.
The synthetic utilization of rhodium(II) acetate dimer catalyzed
2. Results and discussion
reactions of a-diazocarbonyl compounds to synthesize a variety of
The starting material diazo amide 4a was synthesized5 from
-ornithine monohydrochloride by alumina catalyzed cyclization
and then diazotization. N-Alkylation reactions of 3-diazopiperidin-
2-ones were performed to yield various substituted 3-hetero-
arylpiperidin-2-one systems. Towards this, 3-diazopiperidin-2-one
was treated with sodium hydride in DMF at 0 ꢀC and then various
alkyl halides such as methyl iodide, allyl bromide or benzyl
molecular architectures and biologically interesting molecules is
well documented.1 Besides, the ever-growing synthetic applica-
tions of this protocol to synthesize biologically important mole-
cules make the immense involvement into this methodology.
L
Transition metal catalyzed carbenoid insertion reactions of
a-
diazocarbonyl compounds are one of the most important tools in
synthetic organic chemistry.2 Generally, these metallo-carbenoid
methodologies are known to provide various functionalized mole-
cules via C–C bond formation with selectivity.
Br
O
H
N
3-Aryl/heteroaryl substituted N-containing heterocycles and
their derivatives have been thoroughly investigated in the last two
decades in view of their important biological properties,3 for
example, bis-indole alkaloid 1,3a,b 3-arylpiperidine derivatives
23c,d and preclamol 33e (Fig. 1). In continuation of our ongoing
Br
NH
HN
HN
1; Bis-indole alkaloid
OH
research work4 on
a-diazocarbonyl compounds, we herein report
the synthesis of (3-indol-3-yl-) or (3-pyrrol-2-yl)piperidones
Aryl
and diazacyclopenta[a]phenalenone via Rh2(OAc)4 catalyzed
N
R
N
R
2; 3-Arylpiperidines
3; Preclamol
* Corresponding author. Tel.: þ91 431 2407053; fax: þ91 431 2407045.
E-mail address: muthu@bdu.ac.in (S. Muthusamy).
Figure 1.
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.12.070

1568
S. Muthusamy, P. Srinivasan / Tetrahedron 65 (2009) 1567–1573
bromide to give the corresponding N-alkylated diazo derivatives
4b–d (Scheme 1).
These regioselective C-alkylation reactions of diazoamides 4
were further demonstrated by performing the reactions with
substituted or unsubstituted pyrroles. Towards this, reaction of
diazo amide 4a and unsubstituted pyrrole 7a with a catalytic
amount of rhodium(II) acetate was resulted the C-alkylation at the
electron rich 2-position of pyrrole to afford product 8a (Scheme 3,
Table 2, entry a) with complete regio- and chemoselectivity.
Similar C-alkylation reaction was further extended with various
substituted pyrroles and 3-diazopiperidin-2-ones to furnish several
3-pyrrolylpiperidin-2-ones 8b–g. We did not observe the corre-
sponding N–H insertion product even in the absence of substitution
on pyrrole N-atom. This is in contrary to our previous report,6
where the rhodium catalyzed reaction of diazo amide 4 is known to
furnish N–H insertion product with indoles.
N2
O
N2
O
NaH/DMF
0 °C
R1X
+
N
H
N
R1
4b-d
4a
4b; R1 = Me; 94%
4c; R1 = allyl; 85%
4d; R1 = benzyl; 87%
Scheme 1. Synthesis of N-alkylated 3-diazopiperidin-2-ones.
Initially, we investigated the carbenoid reaction of 3-diazo-
piperidin-2-one 4a with N-methylindole 5a using Rh2(OAc)4 cata-
lyst in dichloromethane at room temperature furnishing 6a in 80%
yield (Table 1, entry a) via C-alkylation at 3-position of indole.
R3
R2
N
N2
Rh2(OAc)4
CH2Cl2, rt
+
R3
N
N
R1
4
O
R2
N
O
Table 1
R1
7
8
Synthesis of 3-indolylpiperidin-2-ones 6
Scheme 3. Reaction of 3-diazopiperidin-2-ones with pyrroles.
Entry
R1
R2
R3
Product
Time (min)
Yielda (%)
a
b
c
d
e
f
g
h
i
H
H
Me
Allyl
Me
H
H
H
H
H
H
H
H
H
Br
6a
6b
6c
6d
6e
6f
6g
d
d
d
20
15
15
15
15
25
30
240
240
240
80
81
78
85
89
72
75
d
d
d
Diazo amide 4a was treated under similar reaction condition
with 2-allylpyrrole where the 2-position of pyrrole is blocked. Here,
the carbenoid has underwent C-alkylation to 5-position of pyrrole
(but not to the 3-position) when 2-position is blocked by the allyl
group (entry 8d).
Me
Allyl
Allyl
Me
Me
Me
Allyl
H
Me
Allyl
Benzyl
Allyl
COMe
Ts
j
Allyl
Table 2
a
Yields (unoptimized) refer to isolated pure compounds 6.
Synthesis of 3-pyrrolylpiperidin-2-ones 8
Entry
R1
R2
R3
Product
Time (min)
Yielda (%)
a
b
c
d
e
f
H
H
H
H
H
H
Allyl
H
H
H
H
8a
8b
8c
8d
8e
8f
20
15
15
15
25
15
240
240
85
79
88
75
75
85
d
Further, we elaborated this carbenoid reaction with different N-
substituted indoles 5 and -diazoamides 4 to afford the corre-
sponding 3-indolylpiperidin-2-ones 6b–h (Scheme 2, Table 1) in
good yields with regioselectivity. All these rhodium carbenoid re-
actions proceeded readily at room temperature only with 0.5 mol %
of the rhodium(II) acetate catalyst.
Benzyl
H
H
Allyl
H
Benzyl
Allyl
H
a
H
Benzyl
COPh
COMe
g
h
8g
8h
Me
d
a
Yields (unoptimized) refer to isolated pure compounds 8.
N2
+
R3
N
N
O
R2
R1
Rh(II)-catalyzed carbenoid reactions of diazoamides were per-
formed at room temperature and no significant improvement in
yield observed by elevating the temperature of the reaction me-
dium. When the reaction was conducted at 0 ꢀC, diazo amide 4
remained unaffected and the decomposition of diazo group was
observed with evolution of nitrogen bubbles only at the tempera-
ture of the reaction reaches 13 ꢀC. Diazoamides 4 remained un-
affected or unreacted when the above experiments were carried
out in the presence of copper(II) acetoacetonate or copper(II) ace-
toacetate as the catalyst for diazo decomposition. No carbenoid
reactions were observed when diazoamides 4 treated with indoles
having electron withdrawing substituents such as N-acetylindole
5h, N-tosylindole 5i, 5-bromo-1-allyl-1H-indole 5j. These obser-
vations could support the anticipated mechanism for the formation
of alkylation products, which will proceed through the formation of
the zwitterionic intermediate 9. The intermediate 9 carries positive
charge on the indole ring, which could likely be stabilized by the
electron rich substituent on N-atom of indole or pyrrole (Fig. 2).4a
The zwitterion can be anticipated to be formed from the direct
nucleophilic substitution or the cleavage of the initially formed
cyclopropane products derived from diazo amide 4 and indole or
5
4
Rh2(OAc)4
CH2Cl2, rt
R2
N
R3
O
N
R1
6
Scheme 2. Reaction of 3-diazopiperidin-2-ones with N-alkylated indoles.
The reaction of diazoamides 4a/4c with 2-methylindole or 1,2-
dimethyl- or 1-allyl-2-methylindoles did not furnish any expected
alkylation products. In our previous report,6 we have described the
N–H insertion reactions of 3-diazopiperidin-2-ones with various
aromatic amines and indoles with chemoselectivity and observed
the exceptional reactivity of the diazo amide 4 towards the N–H
bonds. Whereas the Rh(II)-catalyzed reactions of diazoamides 4
with N-protected indoles gave the C-alkylation products at 3-
position.

S. Muthusamy, P. Srinivasan / Tetrahedron 65 (2009) 1567–1573
1569
R2
N
N2
+
N
Rh2(OAc)4
N
N
O
N2
CH2Cl2, rt
90%
N
O
N2
O
N
O
9
O
Ac
11
R1
15
Ac
14
Rh2(OAc)4
PhH,
Figure 2. The possible formation of the zwitterionic intermediates.
90%
Rh2(OAc)4
H
N
CH2Cl2, PhH
, 85%
pyrrole in the presence of Rh(II) catalyst. Finally, the proton transfer
of the zwitterion intermediate forms the C-alkylation product.
Next, we planned to utilize this rhodium carbenoid reaction to
synthesize some interesting fused heterocyclic system. Thus, we
aimed to employ the combination of carbenoid reaction and ylide
formation methodologies in a tandem manner. For this purpose,
the substitution on diazo amide 4a was extended to derive another
diazo functional group using diketene acetone adduct and meth-
anesulfonyl azide to afford the bis-diazoimide 11 (Scheme 4).
N
N
O
N
O
O
H
O
Ac
Ac
17
16
H
N
N
O
O
N2
O
N2
18; allomatridine
Scheme 6. Rh(II)-catalyzed C-alkylation and cycloaddition reactions.
O
MsN3, NEt3
5a
N
O
N
O
O
N2
toluene or
xylene,
reflux
CH2Cl2, 0 °C
group has got decomposed to give undetected junk products
(Scheme 5). When bis-diazoimide 11 was treated with N-allylpyr-
role 14 in dichloromethane at room temperature, the cyclic diazo
group got selectively decomposed in the presence of Rh2(OAc)4 at
room temperature to furnish the corresponding C-alkylation
product 15 at 2-position of pyrrole as described in Scheme 6. The IR
O
O
10
11
Scheme 4. Synthesis of bis-diazoimide.
The IR spectrum of diazoimide 11 showed two diazo functional
groups at 2114 and 2099 cmꢁ1. We have planned Rh-catalyzed re-
action of the bis-diazoimide 11 to perform the alkylation as well as
cycloaddition reactions to get rather interesting polycyclic com-
pound. Thus, Rh2(OAc)4 catalyzed reaction of bis-diazoimide 11 and
N-allylindole gave the carbenoid C-alkylation product to yield the
interesting diazoimide 13 in 88% yield. Similarly, diazoimide 10 was
treated with N-allylindole to furnish the alkylated product 12,
which can, in turn, be converted into the corresponding diazoimide
13 upon carrying out diazotization of the active methylene group
using standard literature procedure. This diazoimide 13 was
allowed to react with rhodium(II) acetate using benzene as the
solvent under reflux. This gives no cycloaddition product; the diazo
spectrum of compound 13 showed a strong peak at 2102 cmꢁ1
,
which is characteristic of the presence of diazo functional group.
Even though the starting material has two diazo groups, successful
selective decomposition of the cyclic diazo group was performed.
The acyclic diazo functional group remain unaffected despite the
presence of rhodium(II) acetate catalyst. No cyclopropanation
products were obtained via the diazo group and olefin present on
allyl group. Diazoimide 15 was further treated with Rh(II)-catalyst
in benzene under reflux to afford the corresponding interesting
polycyclic system 16 with 90% yield in a diastereoselective manner
(Scheme 6). 1H and 13C NMR spectral analyses confirmed the for-
mation of a single isomer. The energy minimization calculations
were performed at MM2 level and the stereochemistry was ten-
tatively assigned based on these calculations. The skeletal structure
of the cycloadduct 16 is closely related to an alkaloid,
allomatridine.7
Mechanistically, the rhodium(II)-carbenoid derived from diazo-
imide 11 furnished isomu¨nchnone 17 as an intermediate, which
subsequently underwent the intramolecular 1,3-dipolar cycload-
dition to the olefin functionality. These reaction steps could also be
performed in a one pot manner. Thus, diazoimide 11 was allowed to
react with N-allylpyrrole in the presence of rhodium(II) acetate
catalyst in dichloromethane and then evaporated the solvent
yielding the crude reaction mixture under nitrogen atmosphere. To
the above crude reaction mixture, benzene was added and refluxed
for 30 min to afford product 16 in a single step via tandem in-
sertion–cyclization–cycloaddition methodology. These reactions
represent an important methodology to generate complex poly-
cyclic systems from simple starting materials.
N
Rh2(OAc)4
CH2Cl2, rt
90%
10 N-allylindole
+
N
O
O
12
Ac
CH2Cl2, NEt3,
0 °C
MsN3
N
Rh2(OAc)4
11 N-allylindole
+
CH2Cl2, rt
88%
N
O
N2
O
13
Ac
3. Conclusion
PhH, reflux
Rh2(OAc)4
no cycloaddition
Scheme 5. Reactions of diazoimides with N-allylindole.
In conclusion, we have described a mild and convenient
regioselective method to synthesize indol-3-yl- or pyrrol-3-ylpi-
peridones in good yield in the presence of Rh2(OAc)4 catalyst.

1570
S. Muthusamy, P. Srinivasan / Tetrahedron 65 (2009) 1567–1573
This protocol is
a
versatile method for various hetero-
2086, 1609, 1483, 1461, 1438, 1356, 1216, 927, 755 cmꢁ1 1H
;
arylpiperidines. The carbenoid reaction with pyrrole afforded 2-
pyrrolylpiperidones with chemoselectivity. The Rh2(OAc)4
catalyzed reaction of bis-diazoimide furnished the dia-
zacyclopenta[a]phenalenone ring system in a tandem manner
with diastereoselectivity.
(200 MHz, CDCl3) 5.86–5.66 (1H, m), 5.17 (2H, d, J¼11.5 Hz), 4.06–
3.88 (2H, m), 3.54–3.20 (2H, m), 2.96–2.76 (2H, m), 1.78–1.64 (2H,
m); 13C (50.3 MHz, CDCl3) 163.1 (C]O), 133.8 (CH), 117.9 (CH2), 50.1
(CH2), 46.9 (CH2), 22.6 (CH2), 22.2 (CH2). HRMS (ESI): MNaþ, found
188.0793; C8H11N3O requires 188.0800.
4. Experimental section
4.1. General
4.2.2. 1-Benzyl-3-diazopiperidin-2-one (4d)
Sodium hydride, 60% in wax (770 mg, 19.2 mmol), was taken in
positive nitrogen flow and washed with 20 mL of dry hexane for
three times. To this 50 mL of dry DMF was added. Diazo amide 4a
(2 g, 16 mmol) dissolved in 10 mL of DMF was added to the stirred
suspension of sodium hydride at 0 ꢀC. After 15 min benzyl bromide
(2.3 mL, 19.2 mmol) was added. Further workup as described in the
previous steps gave the title compound 4d (2.9 g, 87%) as a yellow
liquid. Rf (55% EtOAc/hexane) 0.55; nmax (Neat) 3323, 3261, 2890,
All reactions were carried out in oven-dried glassware under an
atmosphere of argon. All solvents were freshly purified by distil-
lation. All the starting materials used are purchased from Aldrich. IR
spectra were recorded using KBr or CH2Cl2 on a Perkin–Elmer
Spectrum GX FT-IR spectrometer. 1H NMR and 13C NMR spectra
were recorded (200 and 50.3 MHz, respectively) on a Bruker
Avance DPX 200 spectrometer using CDCl3. Chemical shifts for
2092, 1617, 1479, 1400, 1339, 792, 639 cmꢁ1 1H (200 MHz, CDCl3)
;
7.27 (5H, s), 4.60 (2H, s), 3.15 (2H, t, J¼5.2 Hz), 2.74–2.68 (2H, m),
1.87–1.78 (2H, m); 13C (50.3 MHz, CDCl3) 164.9 (C]O), 137.7 (quat-
C), 128.9 (CH), 128.3 (CH), 127.7 (CH), 50.7 (CH2), 46.7 (CH2), 22.3
(CH2), 21.8 (CH2). HRMS (ESI): MNaþ, found 238.0962; C12H13N3O
requires 238.0956.
proton and carbon resonances are reported in parts per million (
relative to tetramethylsilane ( 0.00) and chloroform ( 77), re-
d)
d
d
spectively. Multiplicities are indicated by singlet (s), doublet (d),
triplet (t), quartet (q), multiplet (m) and br s (broad singlet). Cou-
pling constants (J) were reported in hertz (Hz). Carbon types were
determined from 13C NMR and DEPT-135 experiments. High reso-
lution mass analyses were performed using electrospray ionization
(ESI) technique on a Waters QTof-micro mass spectrometer. Mi-
croanalysis (C, H, N) was performed using a Perkin–Elmer 4100
elemental analyzer. Analytical thin layer chromatography (TLC) was
performed on silica and components were visualized by observa-
tion under iodine, UV-light or sulfuric acid charring. Column
chromatography was performed on a silica gel (100–200 mesh)
column.
4.3. General experimental procedure for the synthesis
of compounds (6 and 8)
3-(1-Alkyl-1H-indol-3-yl)piperidin-2-one (6): a 50 mL two-
necked round bottomed flask was charged with diazo amide 4
(2 mmol) and N-alkylindole or pyrrole (2.2 mmol) and the flask
fluxed with argon using vacuum. Under argon positive flow, 50 mL
of freshly distilled dichloromethane and stirred well. Rhodium(II)
acetate dimer (0.5 mol %) was added and shortly after, rapid evo-
lution of N2 was observed. Argon atmosphere has been maintained
throughout the course of the reaction. The progress of the reaction
mixture was monitored by using TLC. The solvent was removed
under reduced pressure. The crude reaction mixture was subjected
to column chromatography using silica gel to furnish the C-alky-
lated products.
4.2. General experimental procedure for the synthesis
of 3-diazomethylpiperidin-2-one (4b)
Sodium hydride, 60% in wax (770 mg, 19.2 mmol), was taken in
positive nitrogen flow and washed with 20 mL of dry hexane for
three times. To this 50 mL of dry DMF was added. 3-Diazopiper-
idin-2-one (4a) (2 g, 16 mmol) dissolved in 10 mL of DMF was
added to the stirred suspension of sodium hydride at 0 ꢀC. After
15 min iodomethane (1.2 mL, 19.2 mmol) was added in drops. The
temperature was maintained for 20 min at 0 ꢀC. The progress of
the reaction mixture was monitored using TLC. Then the reaction
mixture was poured into 200 mL of ice-cold water and extracted
with dichloromethane (3ꢂ25 mL). The combined organic layers
were washed thoroughly with water and stored over dry sodium
sulfate. The DCM layer was evaporated and the flash column
chromatography of the reaction mixture over alumina furnished
the title compound 4b (2.1 g, 94%) as a yellow liquid. Rf (70%
EtOAc/hexane) 0.58; nmax (Neat) 3311, 3258, 2898, 2089, 1640,
4.3.1. 3-(1-Methyl-1H-indol-3-yl)piperidin-2-one (6a)
Diazo amide 4a (250 mg, 2 mmol) was allowed to react with
N-methylindole (290 mg, 2.2 mmol) in 50 mL of freshly distilled
dichloromethane in the presence of 0.5 mol % Rh2(OAc)4 as de-
scribed in the general procedure to afford the title compound 6a
(80%) as a brownish solid. [Found: C, 73.51; H, 7.23; N, 12.38.
C14H16N2O requires: C, 73.66; H, 7.06; N, 12.27.] Rf (50% EtOAc/
hexane) 0.6; mp 75–76 ꢀC; nmax (KBr) 3313, 3211, 2940, 1656, 1495,
1428, 1319, 1097, 824, 651 cmꢁ1 1H (200 MHz, CDCl3) 7.55 (1H, d,
;
J¼7.8 Hz, arom-H), 7.29–7.04 (4H, m), 6.96 (1H, s, arom-H), 4.08–
3.92 (1H, m), 3.73 (3H, s, CH3), 3.46–3.24 (2H, m), 2.29–2.01 (1H, m),
1.99–1.67 (3H, m); 13C (50.3 MHz, CDCl3) 175.4 (C]O), 136.8 (quat-
C), 127.7 (CH), 127.2 (quat-C), 122.1 (CH), 119.6 (CH), 119.4 (CH),
109.6 (CH), 43.1 (CH2), 40.2 (CH), 33.2 (CH3), 29.7 (CH2), 21.4 (CH2);
MS (EI) m/z 228 (Mþ, 20%), 1205 (8), 119 (20), 115 (33), 87 (48), 70
(14), 59 (62), 44 (100).
1482, 1411, 1348, 794, 638 cmꢁ1 1H (200 MHz, CDCl3) 3.12 (2H, t,
;
J¼5.2 Hz), 2.84–2.57 (5H, m), 1.78–1.75 (2H, m); 13C (50.3 MHz,
CDCl3) 162.2 (C]O), 48.8 (CH2), 34.7 (CH3), 21.8 (CH2), 21.3
(CH2). HRMS (ESI): MNaþ, found 162.0651; C6H9N3O requires
162.0643.
4.3.2. 3-(1-Allyl-1H-indol-3-yl)piperidin-2-one (6b)
4.2.1. 1-Allyl-3-diazopiperidin-2-one (4c)
Diazo amide 4a (250 mg, 2 mmol) was allowed to react with
N-allylindole (345 mg, 2.2 mmol) in 50 mL of dichloromethane at
room temperature in the presence of 0.5 mol % Rh2(OAc)4 as de-
scribed in the above procedure to afford the title compound 6b
(81%) as a yellow solid. [Found: C, 75.80; H, 7.10; N,11.07. C16H18N2O
requires: C, 75.56; H, 7.13; N, 11.01%.] Rf (50% EtOAc/hexane) 0.58;
mp 74–75 ꢀC; nmax (KBr) 3413, 3061, 1637, 1496, 1451, 1265, 1169,
Sodium hydride, 60% in wax (770 mg, 19.2 mmol), was taken in
positive nitrogen flow and washed with 20 mL of dry hexane for
three times. To this 50 mL of dry DMF was added. Diazo amide 4a
(2 g, 16 mmol) dissolved in 10 mL of DMF was added to the stirred
suspension of sodium hydride at 0 ꢀC. After 15 min allyl bromide
(1.7 mL, 19.2 mmol) was added. Further workup as described in the
previous steps gave the title compound 4c (2.2 g, 85%) as a yellow
liquid. Rf (60% EtOAc/hexane) 0.6; nmax (Neat) 3005, 2962, 2863,
1121, 734 cmꢁ1
;
1H (200 MHz, CDCl3) 7.56 (1H, d, J¼7.3 Hz, arom-
H), 7.26–7.08 (3H, m, arom-H), 6.99 (1H, s, arom-H), 6.8 (1H, br s,

S. Muthusamy, P. Srinivasan / Tetrahedron 65 (2009) 1567–1573
1571
NH), 5.98–5.92 (1H, m, CH), 5.22–5.16 (2H, m, CH2), 4.69–4.65 (2H,
m, CH2), 3.98 (1H, t, J¼3.2 Hz, CH2), 3.46–3.32 (2H, m, NCH2), 2.27–
2.20 (1H, m), 1.94–1.78 (3H, m); 13C (50.3 MHz, CDCl3) 171.6 (C]O),
136.5 (quat-C), 134.2 (CH), 127.8 (quat-C), 126.7 (CH), 120.3 (CH),
119.9 (CH), 119.8 (CH), 118.1 (CH2), 115.4 (quat-C), 110.4 (CH), 49.5
(CH2), 43.4 (CH2), 40.4 (CH), 29.6 (CH2), 21.4 (CH2). MS (EI) m/z 255
(Mþ1)þ.
C
21H22N2O requires: C, 79.21; H, 6.96; N, 8.80%.] Rf (50% EtOAc/
hexane) 0.55; mp 95–96 ꢀC; nmax (KBr) 3334, 3269, 2893, 2718,
1625, 1480, 1407, 1344, 790, 639 cmꢁ1 1H (200 MHz, CDCl3) 7.51
;
(1H, d, J¼8.4 Hz, arom-H), 7.31–7.04 (8H, m, arom-H), 6.95 (1H, s,
arom-H), 5.25 (2H, s), 4.01 (1H, t, J¼6.4 Hz), 3.44–3.27 (2H, m, CH2),
3.04 (3H, s), 2.21–1.72 (4H, m); 13C (50.3 MHz, CDCl3) 171.7 (C]O),
137.7 (quat-C), 137.5 (quat-C), 128.8 (CH), 128.5 (CH), 127.3 (CH),
127.6 (CH), 122.3 (CH), 119.4 (CH), 119.2 (CH), 115.0 (quat-C), 109.9
(CH), 50.4 (CH2), 40.7 (CH), 34.4 (CH3), 29.8 (CH2), 21.5 (CH2). MS
(EI) m/z 318.
4.3.3. 1-Methyl-3-(1-methyl-1H-indol-3-yl)piperidin-2-one (6c)
Diazo amide 4b (280 mg, 2 mmol) was allowed to react with
N-methylindole (290 mg, 2.2 mmol) in 50 mL of freshly distilled
dichloromethane in the presence of 0.5 mol % Rh2(OAc)4 as de-
scribed in the general procedure to furnish the title compound 6c
(78%) as a brownish solid. [Found: C, 74.44; H, 7.52; N, 11.54.
C15H18N2O requires: C, 74.35; H, 7.49; N, 11.56%.] Rf (50% EtOAc/
hexane) 0.6; mp 88–89 ꢀC; nmax (KBr) 3052, 2932, 1636, 1500, 1469,
4.3.7. 1-Methyl-3-(1-allyl-1H-indol-3-yl)piperidin-2-one (6g)
Diazo amide 4b (280 mg, 2 mmol) was allowed to react with
N-allylindole (345 mg, 2.2 mmol) in 50 mL of freshly distilled
dichloromethane in the presence of 0.5 mol % Rh2(OAc)4 as de-
scribed in the general procedure to furnish the title compound 6g
(75%) as a thick brownish oil. [Found: C, 75.95; H, 7.51; N, 10.38.
C17H20N2O requires: C, 76.09; H, 7.51; N, 10.44%.] Rf (50% EtOAc/
hexane) 0.57; nmax (film) 3388, 3054, 1639, 1496, 1244, 1131, 1116,
1325, 735 cmꢁ1
;
1H (200 MHz, CDCl3) 7.52 (1H, d, J¼7.6 Hz, arom-
H), 7.44–7.03 (3H, m, arom-H), 6.85 (1H, s, arom-H), 3.97 (1H, t,
J¼5.9 Hz, CH), 3.68 (3H, s, CH3), 3.48–3.20 (2H, m, NCH2), 3.03 (3H,
s, CH3), 2.13–2.08 (1H, m), 1.928–1.73 (3H, m); 13C (50.3 MHz,
CDCl3) 171.8 (C]O), 137.6 (quat-C), 127.4 (CH), 122.0 (CH), 119.6
(CH), 119.3 (CH), 115.1 (quat-C), 109.8 (CH), 50.8 (CH2), 40.5 (CH),
35.6 (CH3), 33.1 (CH3), 29.6 (CH2), 21.4 (CH2). MS (EI) m/z 242.
738 cmꢁ1
;
1H (200 MHz, CDCl3) 7.53 (1H, d, J¼3.5 Hz, arom-H),
7.29–7.04 (3H, m, arom-H), 6.90 (1H, s, arom-H), 5.98–5.91 (1H, m,
CH), 5.19–5.15 (2H, m, CH2), 4.66 (2H, d, J¼5.4 Hz, CH2), 3.98 (2H, d,
J¼3.1 Hz, CH2), 3.44–3.28 (2H, m, NCH2), 2.98 (3H, s, CH3), 2.19–1.55
(4H, m); 13C (50.3 MHz, CDCl3) 171.0 (C]O), 136.5 (quat-C), 133.5
(CH), 127.2 (quat-C), 125.8 (CH), 121.4 (CH), 119.2 (CH), 118.9 (CH),
117.1 (CH2), 114.9 (quat-C), 109.6 (CH), 50.2 (CH2), 48.7 (CH2), 39.9
(CH), 35.0 (CH3), 28.9 (CH2), 20.8 (CH2). MS (EI) m/z 268.
4.3.4. 1-Allyl-3-(1-methyl-1H-indol-3-yl)piperidin-2-one (6d)
Diazo amide 4c (330 mg, 2 mmol) was allowed to react with
N-methylindole (290 mg, 2.2 mmol) in 50 mL of dichloromethane
at room temperature in the presence of 0.5 mol % of Rh2(OAc)4 as
described in the above procedure to afford the title compound 6d
(85%) as a brownish thick oil. [Found: C, 75.89; H, 7.47; N, 10.34.
C17H20N2O requires: C, 76.09; H, 7.51; N, 10.44%.] Rf (45% EtOAc/
hexane) 0.6; nmax (film) 3394, 3055, 1641, 1486, 1264, 1172, 1120,
739 cmꢁ1; 1H (200 MHz, CDCl3) 7.51 (1H, t, J¼7.4 Hz, arom-H), 7.48–
7.02 (3H, m, arom-H), 6.83 (1H, d, J¼5.7 Hz, arom-H), 5.81–5.74 (1H,
m), 5.23–5.08 (2H, m), 4.1–3.91 (3H, m), 3.64 (3H, s, CH3), 3.36–3.23
(2H, m), 2.11–2.06 (1H, m), 1.92–1.62 (3H, m); 13C (50.3 MHz, CDCl3)
170.3 (C]O), 136.7 (quat-C), 132.7 (CH), 127.2 (quat-C), 126.5 (CH),
121.1 (CH), 118.7 (CH), 118.4 (CH), 117.0 (CH2), 114.9 (quat-C), 109.6
(CH), 48.9 (CH2), 46.6 (CH2), 39.7 (CH), 32.1 (CH3), 28.6 (CH2), 20.6
(CH2). MS (EI) m/z 268 (M,100),183 (50),170 (85),151 (75),144 (60),
109 (70), 77 (28), 41 (88).
4.3.8. 3-(1H-Pyrrol-2-yl)piperidin-2-one (8a)
Diazo amide 4a (250 mg, 2 mmol) was allowed to react with
pyrrole (150 mg, 2.2 mmol) in 50 mL of dichloromethane at room
temperature in the presence of 0.5 mol % of Rh2(OAc)4 as described
in the above procedure to afford the title compound 8a (85%) as
a thick brownish liquid. [Found: C, 65.95; H, 7.30; N, 17.27.
C9H12N2O requires: C, 65.83; H, 7.37; N, 17.06%.] Rf (85% EtOAc/
hexane) 0.62; nmax (film) 3394, 3302, 1654, 1491, 1355, 1325, 1267,
1100, 734 cmꢁ1; 1H (200 MHz, CDCl3) 9.60 (1H, br s, NH), 6.78 (1H,
br s, NH), 6.72 (1H, s, arom-H), 6.13 (1H, d, J¼2.5 Hz, arom-H), 5.99
(1H, s, CH), 3.61 (1H, t, J¼7.0 Hz), 3.30–3.24 (2H, m), 2.32–1.64 (4H,
m); 13C (50.3 MHz, CDCl3) 173.7 (C]O), 129.9 (quat-C), 117.9 (CH),
108.2 (CH), 104.9 (CH), 43.1 (CH2), 39.9 (CH), 26.3 (CH2), 19.8 (CH2).
MS (EI) m/z 164 (Mþ, 43), 149 (12), 133 (25), 119 (15), 106 (8), 99
(100), 91 (14), 70 (28), 55 (38), 43 (42).
4.3.5. 1-Allyl-3-(1-allyl-1H-indol-3-yl)piperidin-2-one (6e)
Diazo amide 4c (330 mg, 2 mmol) was allowed to react with
N-allylindole (345 mg, 2.2 mmol) in 50 mL of dichloromethane at
room temperature in the presence of 0.5 mol % of Rh2(OAc)4 as
described in the above procedure to afford the title compound 6e
(89%) yield as a brownish solid. [Found: C, 77.63; H, 7.59; N, 9.40.
C19H22N2O requires: C, 77.52; H, 7.53; N, 9.52%.] Rf (45% EtOAc/
hexane) 0.55; mp 65–66 ꢀC; nmax (KBr) 3341, 3291, 2944, 1662,
4.3.9. 3-(1-Benzyl-1H-pyrrol-2-yl)piperidin-2-one (8b)
Diazo amide 4a (250 mg, 2 mmol) was allowed to react with
N-benzylpyrrole (475 mg, 2.2 mmol) in 50 mL of dichloromethane
at room temperature in the presence of 0.5 mol % Rh2(OAc)4 as
described in the general procedure to afford the title compound 8b
(79%) as a thick brownish liquid. [Found: C, 75.70; H, 7.02; N, 11.21.
C16H18N2O requires: C, 75.56; H, 7.13; N, 11.01%.] Rf (50% EtOAc/
hexane) 0.60; nmax (film) 3339, 3298, 3055, 2931, 1642, 1495, 1453,
1265, 737 cmꢁ1; 1H (200 MHz, CDCl3) 7.34–7.30 (3H, m), 7.03–6.99
(2H, m), 6.62 (1H, d, J¼1.5 Hz), 6.30 (1H, br s), 6.15 (1H, t, J¼1 Hz),
6.06 (1H, s), 5.36 (1H, d, J¼16.4 Hz, benzylic H), 5.11 (1H, d,
J¼16.4 Hz, benzylic H), 3.47 (1H, t, J¼8.3 Hz, CH), 3.42–3.31 (2H, m),
1.95–1.27 (4H, m); 13C (50.3 MHz, CDCl3) 172.8 (C]O), 139.4 (quat-
C), 132.0 (quat-C), 129.3 (CH), 127.9 (CH), 127.2 (CH), 122.6 (CH),
107.9 (CH), 107.3 (CH), 51.4 (CH2), 43.2 (CH2), 40.3 (CH), 28.3 (CH2),
22.2 (CH2). MS (EI) m/z 254 (Mþ, 45),170 (20), 156 (45), 135 (12),115
(30), 91 (90), 87 (28), 59 (88), 44 (100).
1495, 1429, 1212, 739 cmꢁ1 1H (200 MHz, CDCl3) 7.55 (1H, d,
;
J¼1.3 Hz, arom-H), 7.29–7.04 (3H, m, arom-H), 6.91 (1H, s, arom-H),
5.95–5.90 (2H, m), 5.26–5.14 (4H, m), 4.67–4.63 (2H, m), 4.12–3.95
(3H, m), 3.40–3.31 (2H, m), 2.18–1.81 (4H, m); 13C (50.3 MHz,
CDCl3) 170.5 (C]O), 136.4 (quat-C), 133.4 (CH), 132.9 (CH), 127.1
(quat-C), 125.6 (CH), 121.3 (CH), 119.1 (CH), 118.8 (CH), 117.2 (CH2),
117.1 (CH2), 114.8 (quat-C), 109.5 (CH), 49.6 (CH2), 48.6 (CH2), 47.4
(CH2), 40.1 (CH), 28.8 (CH2), 20.9 (CH2); MS (EI) m/z 294 (Mþ, 80),
196 (20), 168 (40), 154 (35), 109 (45), 55 (28), 44 (100), 42 (80).
4.3.6. 1-Methyl-3-(1-benzyl-1H-indol-3-yl)piperidin-2-one (6f)
Diazo amide 4b (280 mg, 2 mmol) was allowed to react with
N-benzylindole (290 mg, 2.2 mmol) in 50 mL of freshly distilled
dichloromethane in the presence of 0.5 mol % Rh2(OAc)4 as de-
scribed in the general procedure to furnish the title compound 6f
(72%) as a brownish solid. [Found: C, 78.99; H, 7.00; N, 8.84.
4.3.10. 1-Allyl-3-(1H-pyrrol-2-yl)piperidin-2-one (8c)
Diazo amide 4c (330 mg, 2 mmol) was allowed to react with
pyrrole (150 mg, 2.2 mmol) in 50 mL of dichloromethane at room
temperature in the presence of 0.5 mol % of Rh2(OAc)4 as described

1572
S. Muthusamy, P. Srinivasan / Tetrahedron 65 (2009) 1567–1573
in the above procedure to afford the title compound 8c (88%) as
a thick brownish liquid. [Found: C, 70.49; H, 7.92; N, 13.80.
C12H16N2O requires: C, 70.56; H, 7.90; N, 13.71%.] Rf (55% EtOAc/
hexane) 0.62; nmax (film) 3076, 3055, 2939, 2867, 1634, 1489, 1349,
mixture refluxed at 130 ꢀC for 2 h. The progress of the reaction was
monitored using TLC and after the completion of the reaction the
solvent evaporated using vacuum. The resulting solid was subjected
to flash column chromatography over silica using N2 to give the title
compound 10 (125 mg, 80%) as a yellow liquid. [Found: C, 51.75; H,
5.28; N, 20.04. C9H11N3O3 requires: C, 51.67; H, 5.30; N, 20.09%.] Rf
(65% EtOAc/hexane) 0.61; nmax (Neat) 3339, 2940, 2100, 1653, 1648,
1275, 1194, 926, 741 cmꢁ1 1H (200 MHz, CDCl3) 9.45 (1H, br s,
;
pyrrole-NH), 6.73 (1H, s, arom-H), 6.13 (1H, d, J¼2.8 Hz, arom-H),
5.98 (1H, s, CH), 5.77–5.68 (1H, m, allylic), 5.18–5.08 (2H, m, CH2),
4.06–3.94 (2H, m, NCH2), 3.67 (1H, t, J¼6.7 Hz, CH2), 3.31–3.25 (2H,
m, NCH2), 2.31–1.55 (4H, m); 13C (50.3 MHz, CDCl3) 170.9 (C]O),
133.1 (CH), 130.2 (quat-C), 118.1 (CH2), 117.9 (CH), 108.2 (CH), 104.6
(CH), 50.5 (CH2), 48.4 (CH2), 40.4 (CH), 26.5 (CH2), 22.1 (CH2). MS
(EI) m/z 204.
1460, 1172, 739 cmꢁ1 1H (200 MHz, CDCl3) 4.02 (s, 2H), 3.8–3.77
;
(2H, m, NCH2), 2.78 (2H, t, J¼6.2 Hz, NCH2), 2.25 (3H, s, CH3), 1.95–
1.87 (2H, m); 13C (50.3 MHz, CDCl3) 201.1 (C]O),167.2 (C]O),166.2
(C]O), 58.1 (quat-C), 53.9 (CH2), 44.9 (CH2), 29.7 (CH3), 21.0 (CH2),
20.9 (CH2); MS (EI) m/z 209 (Mþ, 209).
4.3.11. 3-(5-Allyl-1H-Pyrrol-2-yl)piperidin-2-one (8d)
4.3.15. 2-Diazo-1-(3-diazo-2-oxopiperidin-1-yl)butane-
Diazo amide 4a (250 mg, 2 mmol) was allowed to react with
3-allylpyrrole (150 mg, 2.2 mmol) in 50 mL of dichloromethane at
room temperature in the presence of 0.5 mol % of Rh2(OAc)4 as
described in the above procedure to afford the title compound 8d
(75%) as a thick brownish liquid. [Found: C, 70.61; H, 7.85; N, 13.47.
C12H16N2O requires C, 70.56; H, 7.90; N, 13.71%.] Rf (50% EtOAc/
hexane) 0.55; nmax (film) 3339, 3292, 2951, 1656, 1490, 1419, 1323,
1,3-dione (11)
1-(3-Diazo-2-oxopiperidin-1-yl)butane-1,3-dione
(10 mmol)
obtained in the previous step was allowed to react with triethyl-
amine (12 mmol) and methanesulfonyl azide (11 mmol) at ice-cold
condition for 10 min. The reaction mixture was allowed to stir at
room temperature for 4 h. After the completion of the reaction by
TLC, the reaction mixture was washed with water, evaporated using
vacuum and the resulting solid was subjected to flash column
chromatography over silica to give the title compound 11 (75%) as
a yellow solid. [Found: C, 45.77; H, 3.99; N, 29.70. C9H9N5O3 re-
quires: C, 45.96; H, 3.86; N, 29.78%.] Rf (65% EtOAc/hexane) 0.52;
mp 52–53 ꢀC; nmax (KBr) 3339, 2940, 2357, 2114, 2099, 1654, 1647,
1266, 737 cmꢁ1 1H (200 MHz, CDCl3) 9.20 (1H, br s, pyrrole–NH),
;
6.55 (1H, s), 5.92–5.72 (3H, m, allylic, arom-H), 5.15–4.92 (2H, m,
CH2), 3.57–3.14 (5H, m), 2.20–1.74 (4H, m); 13C (50.3 MHz, CDCl3)
173.6 (C]O), 139.3 (quat-C), 136.6 (CH), 116.7 (CH2), 114.6 (quat-C),
105.6 (CH), 104.9 (CH), 43.2 (CH2), 40.0 (CH), 33.1 (CH2), 26.1 (CH2),
21.6 (CH2). MS (EI) m/z 204 (Mþ, 48).
1458, 1404, 1257, 1171, 738 cmꢁ1 1H (200 MHz, CDCl3) 3.54 (2H, t,
;
J¼5.4 Hz, NCH2), 2.68 (2H, t, J¼6.4 Hz, NCH2), 2.32 (3H, s, CH3),1.99–
1.86 (2H, m); 13C (50.3 MHz, CDCl3) 189.6 (C]O), 165.0 (C]O),
162.2 (C]O), 65.6 (quat-C), 44.3 (CH2), 28.1 (CH3), 21.3 (CH2), 20.5
(CH2); MS (EI) m/z 235 (Mþ, 235).
4.3.12. 1-Benzyl-3-(1H-pyrrol-2-yl)piperidin-2-one (8e)
Diazo amide 4d (430 mg, 2 mmol) was allowed to react with
pyrrole (150 mg, 2.2 mmol) in 50 mL of dichloromethane at room
temperature in the presence of 0.5 mol % of Rh2(OAc)4 as described
in the above procedure to afford the title compound 8e (75%) yield
as a thick brownish liquid. [Found: C, 75.46; H, 7.19; N, 11.08.
C16H18N2O requires: C, 75.56; H, 7.13; N, 11.01%.] Rf (55% EtOAc/
hexane) 0.58; nmax (film) 3391, 2942, 2915, 2856, 1623, 1552, 1485,
1450, 1346, 1247, 1095, 775 cmꢁ1; 1H (200 MHz, CDCl3) 9.69 (1H, br
s, NH), 7.30–7.19 (5H, m), 6.73 (1H, s), 6.14 (1H, d, J¼2.7 Hz), 5.99
(1H, s), 4.69 (1H, d, J¼14.6 Hz), 4.47 (1H, d, J¼14.6 Hz), 3.72 (1H, t,
J¼6.7 Hz), 3.22–3.16 (2H, m), 2.29–1.69 (4H, m); 13C (50.3 MHz,
CDCl3) 171.1 (C]O), 137.5 (quat-C), 130.2 (quat-C), 129.2 (CH), 128.5
(CH), 128.0 (CH), 117.9 (CH), 108.2 (CH), 104.6 (CH), 51.1 (CH2), 48.4
(CH2), 40.5 (CH), 26.5 (CH2), 22.0 (CH2); MS (EI) m/z 254 (Mþ, 40),
92 (20), 84 (100), 54 (15), 49 (94).
4.3.16. 1-[3-(1-Allyl-1H-indol-2-yl)-2-oxopiperidin-1-yl]-butane-
1,3-dione (12)
Diazo amide 10 (210 mg, 1 mmol) was allowed to react with
N-allylindole (190 mg, 1.2 mmol) in 50 mL of dichloromethane at
room temperature in the presence of 0.5 mol % of Rh2(OAc)4 as
described in the above procedure to afford the title compound 12
(90%) as a yellow solid. Rf (65% EtOAc/hexane) 0.60; mp 104–105 ꢀC;
nmax (KBr) 3424, 2935, 1736, 1651, 1450, 1269, 1075, 738 cmꢁ1 1H
;
(200 MHz, CDCl3) 7.46 (1H, d, J¼7.6 Hz), 7.31–7.06 (3H, m), 6.96 (1H,
s), 5.99–5.91 (1H, m), 5.21–5.06 (2H, m), 4.66 (2H, d, J¼4.2 Hz),
4.10–3.81 (5H, m), 2.26–1.84 (7H, m); 13C (50.3 MHz, CDCl3) 201.5
(C]O), 174.6 (C]O), 169.4 (C]O), 136.3 (quat-C), 133.2 (CH), 126.9
(quat-C), 125.7 (CH), 121.7 (CH), 119.2 (CH), 119.0 (CH), 117.3 (CH2),
112.8 (quat-C), 109.7 (CH), 54.4 (CH2), 48.6 (CH2), 43.5 (CH2), 42.1
(CH), 29.9 (CH3), 27.6 (CH2), 20.9 (CH2). HRMS (ESI): MNaþ, found
361.1511; C20H22N2O3 requires 361.1528.
4.3.13. 1-Allyl-3-(1-benzyl-1H-pyrrol-2-yl)piperidin-2-one (8f)
Diazo amide 4c (330 mg, 2 mmol) was allowed to react with
N-benzylpyrrole (475 mg, 2.2 mmol) in 50 mL of dichloromethane
at room temperature in the presence of 0.5 mol % of Rh2(OAc)4 as
described in the above procedure to afford the title compound 8f
(85%) as a thick brownish liquid. [Found: C, 77.58; H, 7.55; N, 9.61.
C19H22N2O requires: C, 77.52; H, 7.53; N, 9.52%.] Rf (50% EtOAc/
hexane) 0.55; nmax (film) 3342, 3290, 2888, 1637, 1490, 1352, 1421,
1322, 1260, 739 cmꢁ1; 1H (200 MHz, CDCl3) 7.32–7.22 (3H, m), 7.00
(2H, d, J¼6.7 Hz), 6.62 (1H, t, J¼2.2 Hz), 6.15–5.73 (3H, m), 5.48–
5.08 (4H, m), 4.02–3.84 (3H, m), 3.51–3.21 (2H, m), 2.02–1.66 (4H,
m); 13C (50.3 MHz, CDCl3) 169.5 (C]O), 138.9 (quat-C), 132.8 (CH),
131.8 (quat-C), 128.6 (CH), 127.2 (CH), 126.3 (CH), 121.2 (CH2), 117.3
(CH), 107.1 (CH), 106.3 (CH), 50.7 (CH2), 49.7 (CH2), 47.3 (CH2), 39.9
(CH), 21.9 (CH2), 19.3 (CH2). MS (EI) m/z 294 (Mþ, 52).
4.3.17. 1-[3-(1-Allyl-1H-indol-2-yl)-2-oxopiperidin-1-yl]-2-
diazobutane-1,3-dione (13)
Diazo amide 11 (235 mg, 1 mmol) was allowed to react with
N-allylpyrrole (130 mg, 1.2 mmol) in 50 mL of dichloromethane at
room temperature in the presence of 0.5 mol % of Rh2(OAc)4 as
described in the above procedure to afford the title compound 13
(88%) as a yellow solid. Rf (60% EtOAc/hexane) 0.62; mp 107–108 ꢀC;
nmax (KBr) 3433, 2938, 2101, 1738, 1652, 1460, 1401, 1271, 1079,
740 cmꢁ1
;
1H NMR (200 MHz, CDCl3) 7.53 (1H, d, J¼7.4 Hz), 7.32–
7.08 (3H, m), 6.99 (1H, s), 6.01–5.90 (1H, m), 5.22–5.06 (2H, m), 4.67
(2H, d, J¼5.4 Hz), 4.10 (2H, t, J¼6.6 Hz), 3.85 (1H, t, J¼6.0 Hz), 2.45
(3H, s), 2.42–1.79 (4H, m); 13C (50.3 MHz, CDCl3) 189.5 (C]O), 173.5
(C]O), 164.89 (C]O), 136.4 (quat-C), 133.2 (CH), 127.06 (quat-C),
125.5 (CH), 121.9 (CH), 119.4 (CH), 119.1 (CH2), 117.4 (CH), 112.4
(quat-C), 109.8 (CH), 48.7 (CH2), 46.3 (CH2), 41.2 (CH), 28.5 (CH3),
28.3 (CH2), 21.7 (CH2). HRMS (ESI): MNaþ, found 387.1451;
C20H20N4O3 requires 387.1433.
4.3.14. 1-(3-Diazo-2-oxopiperidin-1-yl)butane-1,3-dione (10)
Diazo amide 4a (1 g, 8 mmol) and 2,2,6-trimethyl-[1,3]dioxin-4-
one (1.3 mL, 9 mmol) were taken in a round bottom flask fitted with
a condenser circulating with water at 10 ꢀC under nitrogen atmo-
sphere. To this 50 mL of toluene was added and the reaction

S. Muthusamy, P. Srinivasan / Tetrahedron 65 (2009) 1567–1573
1573
4.3.18. 1-[3-(1-Allyl-1H-pyrrol-2-yl)-2-oxopiperidin-1-yl]-2-
diazobutane-1,3-dione (15)
21.9 (CH2). HRMS (ESI): MNaþ, found 309.1128; C16H18N2O3 re-
quires 309.1215.
Diazo amide 11 (235 mg, 1 mmol) was allowed to react with
N-allylpyrrole (130 mg, 1.2 mmol) in 50 mL of dichloromethane at
room temperature in the presence of 0.5 mol % of Rh2(OAc)4 as
described in the above procedure to afford the title compound 15
(90%) as a yellow solid. Rf (55% EtOAc/hexane) 0.60; mp 72–73 ꢀC;
nmax (KBr) 3434, 2939, 2102, 1734, 1649, 1458, 1404, 1270, 1081,
Acknowledgements
This research was supported by the Ministry of Environment
and Forests, New Delhi. P.S. thanks CSIR, New Delhi for the award of
a research Fellowship.
737 cmꢁ1
;
1H (200 MHz, CDCl3) 6.56 (1H, d, J¼5.8 Hz, arom-H),
6.06–5.86 (3H, m), 5.13–4.86 (2H, m), 4.53–4.36 (2H, m), 3.78–3.73
(3H, m), 2.37 (3H, s), 2.20–1.83 (4H, m); 13C (50.3 MHz, CDCl3) 188.8
(C]O), 172.4 (C]O), 164.2 (C]O), 134.5 (CH), 128.6 (quat-C), 121.3
(CH), 116.0 (CH), 106.8 (CH), 106.5 (CH), 48.9 (CH2), 46.0 (CH2), 41.2
(CH), 28.0 (CH3), 26.9 (CH2), 21.4 (CH2). HRMS (ESI): MNaþ, found
337.1303; C16H18N4O3 requires 337.1277.
References and notes
1. (a) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for Organic
Synthesis with Diazo Compounds. From Cyclopropanes to Ylides; Wiley-Inter-
science: New York, NY, 1998; (b) Davies, H. M. L.; Walji, A. M.; Doyle, M. P. In
Modern Rhodium-Catalyzed Organic Reactions; Evans, P. A., Ed.; Wiley-VCH:
Weinheim, 2005.
2. (a) Gois, P. M. P.; Afonoso, C. M. Eur. J. Org. Chem. 2004, 3773; (b) Muthusamy, S.;
Gunanathan, C.; Babu, S. A.; Suresh, E.; Dastidar, P. Chem. Commun. 2002, 824; (c)
Ye, T.; McKervey, M. A. Chem. Rev. 1994, 94, 1091.
3. (a) Bao, B.; Sun, Q.; Yao, X.; Hong, J.; Chong, O.; Lee, C.-O.; Sim, C. J.; Im, K. S.;
Jung, J. H. J. Nat. Prod. 2005, 68, 711; (b) Gheorghe, A.; Sire, B. Q.; Vila, X.; Zard, S.
Z. Org. Lett. 2005, 7, 1653; (c) Hansson, L. O.; Waters, N.; Holm, S.; Sonesson, C.
J. Med. Chem. 1995, 38, 3121; (d) Macchia, M.; Cervetto, L.; Demontis, G. C.;
Longoni, B.; Minutolo, F.; Orlandini, E.; Ortoce, G.; Papi, C.; Sbrana, A.; Macchia,
B. J. Med. Chem. 2003, 46, 161; (e) Guinchard, X.; Valle´e, Y.; Denis, J.-N. Org. Lett.
2007, 9, 3761; (f) Comins, D. L.; Smith, E. D. Tetrahedron Lett. 2006, 47, 449.
4. (a) Muthusamy, S.; Gunanathan, C. Synlett 2003, 1599; (b) Muthusamy, S.;
Gnanaprakasam, B. Tetrahedron Lett. 2008, 49, 475; (c) Muthusamy, S.; Gna-
naprakasam, B. Tetrahedron Lett. 2007, 48, 6821; (d) Muthusamy, S.; Krishna-
murthi, J. Tetrahedron Lett. 2007, 48, 6692.
5. Hutchinson, I. S.; Matlin, S. A.; Mete, A. Tetrahedron 2002, 58, 3137.
6. Muthusamy, S.; Srinivasan, P. Tetrahedron Lett. 2005, 46, 1063.
7. Fraley, M. E.; Hoffman, W. F.; Arrington, K. L.; Hungate, R. W.; Hartman, G. D.;
MacFall, R. C.; Coll, K. E.; Rickert, K.; Thomas, K. A.; McGaughey, G. B. Curr. Med.
Chem. 2004, 11, 709.
4.3.19. Compound 16
1-(3-Allyl-(1H-pyrrol-2-yl)-2-oxopiperidin-1-yl)-2-diazo-
butane-1,3-dione (100 mg, 3.2 mmol) was refluxed with argon us-
ing vacuum. Under argon positive flow, 40 mL of freshly distilled
benzene was added and stirred well. Rh2(OAc)4 (0.5 mol%) was
added and the mixture refluxed for 1 h to afford the title compound
16 as a colourless solid (90%). Rf (50% EtOAc/hexane) 0.58; mp 85–
86 ꢀC; nmax (KBr) 3427, 3057, 2953, 2864, 1731, 1709, 1455, 1404,
1362, 1270, 1080, 736 cmꢁ1 1H (200 MHz, CDCl3) 6.49 (1H, d,
;
J¼1.6 Hz, arom-H), 6.14 (1H, t, J¼3.2 Hz, arom-H), 6.01 (1H, s, arom-
H), 4.28–4.19 (1H, m), 3.91–3.85 (1H, m), 3.62–3.47 (2H, m), 2.85–
2.71 (2H, m), 2.37 (3H, s), 2.31–2.21 (3H, m), 1.81–1.26 (3H, m); 13C
(50.3 MHz, CDCl3) 200.1 (C]O), 169.7 (C]O), 129.3 (quat-C), 118.5
(CH), 109.1 (CH), 105.1 (CH), 93.0 (quat-C), 89.8 (quat-C), 48.9 (CH2),
38.9 (CH2), 37.3 (CH), 34.2 (CH), 33.6 (CH2), 32.0 (CH2), 27.2 (CH3),