Synthesis of 3-Acylpyrroles, 3-(Alkoxycarbonyl)pyrroles, 1,5,6,7-Tetrahydro-4H-indol-4-ones and 3-Benzoylpyridines Based on Staudinger-Aza-Wittig Reactions of 1,3-Dicarbonyl Compounds with 2- and 3-Azido-1,1-dialkoxy- alkanes

Article abstract of DOI:10.1055/s-0028-1083285

The Staudinger-aza-Wittig reaction of 1,3-dicarbonyl compounds with 2-azido-1,1-diethoxyethane and subsequent cy- clization allowed an efficient synthesis of a variety of pyrroles, 1,5,6,7-tetrahydro-4H-indol-4-ones, and of a pyridine. Georg Thieme Verlag

Full text of DOI:10.1055/s-0028-1083285

PAPER
227
Synthesis of 3-Acylpyrroles, 3-(Alkoxycarbonyl)pyrroles, 1,5,6,7-Tetrahydro-
4H-indol-4-ones and 3-Benzoylpyridines Based on Staudinger–Aza-Wittig
Reactions of 1,3-Dicarbonyl Compounds with 2- and 3-Azido-1,1-dialkoxy-
alkanes
S
taudinger–Aza
s
-Wittig R
e
eactions of
n
1,3-Dicarbonyl Co
B
mpounds ellur,a Mirza A. Yawer,a Ibrar Hussain,a Abdolmajid Riahi,a Olumide Fatunsin,a Christine Fischer,b
Peter Langer*a,b
a
Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
Fax +49(381)4986412; E-mail: peter.langer@uni-rostock.de
Leibniz-Institut für Katalyse e. V. , Universität Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
b
Received 31 July 2008; revised 26 September 2008
intermolecular Staudinger–aza-Wittig reaction of 2-azi-
Abstract: The Staudinger–aza-Wittig reaction of 1,3-dicarbonyl
compounds with 2-azido-1,1-diethoxyethane and subsequent cy-
clization allowed an efficient synthesis of a variety of pyrroles,
1,5,6,7-tetrahydro-4H-indol-4-ones, and of a pyridine.
do-1,1-diethoxyethane with 1,3-dicarbonyl compounds
and subsequent cyclization.9 Herein, we report full details
related to the scope of this method. With regard to our pre-
liminary communication,9 the scope was considerably ex-
tended. In addition, the strategy could be successfully
applied to the synthesis of a functionalized pyridine. All
reactions proceed with very good chemo- and regioselec-
tivity under mild conditions and complement known reac-
tions of 2-amino-1,1-dialkoxyethanes.10
Key words: cyclization, N-heterocycles, pyrroles, azides
Pyrroles, indoles and pyridines are present in many phar-
macologically active natural products. This includes, for
example, the antibiotic pyrrolnitrin, the pyrrolomycins,
various tetrapyrrole pigments (e.g., bilirubin), and various
other natural products and their analogues.1,2 Pentasubsti-
tuted pyrroles are potent hypocholesterolemic agents
which act by inhibition of HMG-CoA reductase – a key
enzyme in the biosynthesis of cholesterol.1i For example,
atorvastatin is used today in the clinic for the treatment of
hyperlipidemias.1i Pyrroles have also found many other
applications in medicinal chemistry. For example, the
synthetic pyrrole zomepirac has been used in the clinic as
an analgetic and antiphlogistic agent.1
2-Azido-1,1-diethoxyethane (2a) and 2-azido-1,1-di-
methoxyethane (2b) were prepared by reaction of sodium
azide with 2-bromo-1,1-diethoxyethane and 2-bromo-1,1-
dimethoxyethane, respectively.8,11 The aza-Wittig reac-
tion of 2a with methyl acetoacetate (1a) afforded enamine
3a (Scheme 1, Tables 1 and 2). Related enamines, pre-
pared from 2-amino-1,1-dimethoxyethane, have been
used for the synthesis of isoquinolines.10b
Optimal results were obtained when the reaction was car-
ried out using a small excess of 2 (1.2 equiv) and of Ph3P
(1.3 equiv) (THF, reflux, 8 h). The transformation of 3a
into the desired pyrrole 4a required a thorough optimiza-
tion of the conditions (Table 1).Treatment of a CH2Cl2 so-
lution of 3a, prepared from methyl acetoacetate (1a), with
TFA at 0–20 °C afforded 4a in 22% yield (method A). The
yield was increased to 35% by treatment of 3a in CH2Cl2
with Me3SiOTf at –78 to 20 °C (method B). Heating of 3a
in DMSO at 150 °C for 24 h afforded 4a in 40% yield
(method C); pyrrole 4a¢ was isolated as a side-product in
19% yield (Figure 1). The use of other solvents than
DMSO (e.g., THF, MeCN or 1,4-dioxane) proved to be
unsuccessful.
Most pyrrole syntheses rely on classical condensation re-
actions, such as the Hantzsch reaction (condensation of a-
haloketones with 1,3-dicarbonyl compounds and amines),
the Paal–Knorr reaction (cyclocondensation of 1,4-dike-
tones with amines) or the Knorr reaction (cyclocondensa-
tion of a-aminoketones with b-keto esters). In addition,
various other synthetic approaches have been devel-
oped.3,4 Intramolecular aza-Wittig reactions5 provide a
versatile approach to pyrroles under mild conditions.6 Re-
cently, we have reported that functionalized pyrroles can
be prepared by reaction of a-azidoketones with 1,3-dicar-
bonyl dianions and subsequent intramolecular
Staudinger–aza-Wittig reaction.7 Pyrroles are also avail-
able by Lewis acid catalyzed condensation of 2-azido-1,1-
dimethoxyethane with silyl enol ethers or 1,3-bis(silyl-
oxy)-1,3-butadienes and subsequent intramolecular
Staudinger–aza-Wittig reaction.8 Recently, we have re-
ported a convenient and versatile approach to pyrroles by
Products 3a–z were prepared by reaction of 1a–w with 2-
azido-1,1-diethoxyethane (2a) and 2-azido-1,1-dimeth-
oxyethane (2b) in 50–98% yields (Table 2). Most yields
were above 80%. Pyrroles 4a–t were successfully pre-
pared from 3a–z using methods A, B, or C in 22–82% op-
timized yields. Methods B and C were successfully
employed for the synthesis of ester-substituted pyrroles
(4a–n). It is worth to be mentioned that pyrroles 4i and 4k
were independently prepared from 2a and 2b. The yields
of the condensation steps (to give enamines 3k,l and 3o,p)
SYNTHESIS 2009, No. 2, pp 0227–0242
x
x
.
x
x
.2
0
0
8
Advanced online publication: 19.12.2008
DOI: 10.1055/s-0028-1083285; Art ID: T12808SS
© Georg Thieme Verlag Stuttgart · New York

228
E. Bellur et al.
PAPER
were quite similar. Likewise, the yields of the cyclization Table 2 Yields of Condensation Products (3) and Pyrroles (4)
steps (to give pyrroles 4i and 4k) were again in the same
1
3
4
R1
R2
R3 Yield
Yield Cond.e
range (method B). These experiments show that equally
successful results are obtained starting with azides 2a and
2b. The reaction of 2a with acetylacetone (1s) afforded 4-
(2,2-diethoxyethylamino)pent-3-en-2-one (3v) which was
transformed into pyrrole 4o (68%) by method A. It is
noteworthy that the Staudinger–aza-Wittig reaction of un-
symmetrical 1,3-diketones 1u–w proceeded with very
good regioselectivity. The cyclization generally occurred
via the central carbon atom of the 1,3-dicarbonyl unit.
(%) (3)a (%) (4)a
a
a
a
OMe
H
Et 86
22
A
B
C
35
40b
b
c
b
c
d
e
f
b
c
d
–
e
f
OEt
H
H
H
H
Et 89
Et 87
Et 88
Et 62
Et 89
Et 90
Et 82
Et 75
Et 78
58
50
42
C
B
B
–
Oi-Pr
Oi-Bu
Ot-Bu
d
e
d
–
OR3
OR3
OR3
N3
f
O(CH2)2OMe H
51
37
39
55
C
B
B
B
–
O
O
O
HN
OR3
2a,b
R1
R1
g
h
i
g
h
i
OAllyl
OMe
OEt
H
R2
R2
i
g
h
–
i
Me
Et
Pr
3a–z
1a–w
R2
H
ii
N
d
j
j
Ot-Bu
OEt
–
R1
k
k
l
k
l
n-C6H13 Me 89
n-C6H13 Et 84
n-C8H17 Et 86
n-C8H17 Et 88
n-C9H19 Me 86b
n-C9H19 Et 91
n-C10H21 Me 90b
n-C10H21 Et 91
(CH2)3Cl Et 83
(CH2)5Cl Et 81
(CH2)6Cl Et 83
60
58
57
B
B
B
–
O
i
OEt
4a–t
m
n
o
p
q
r
s
j
OEt
Scheme 1 Synthesis of 3a–z and 4a–t; Reagents and conditions: i:
Ph3P, THF, reflux, 8 h; ii: see Table 1 and 2. Method A: TFA (10
equiv), CH2Cl2, 0–20 °C, 12 h; method B: Me3SiOTf (1 equiv),
CH2Cl2, –78 to 20 °C (for b-keto esters) or 0–20 °C (for 1,3-di-
ketones), 12 h; method C: DMSO, 150 °C, 24 h.
d
m
n
n
o
o
p
q
r
–
k
k
l
Ot-Bu
OEt
–
57
54
57
56
B
B
B
B
–
OEt
OEt
Table 1 Optimization for the Synthesis of Pyrroles 4a and 4r
l
OEt
3
4
Solvent
Time Conditions
(h)
Yield
(%)a
d
–
m
n
o
OEt
–
a
a
a
a
x
x
x
a
a
a
a
r
r
r
CH2Cl2
CH2Cl2
CH2Cl2
DMSO
CH2Cl2
CH2Cl2
DMSO
12
12
12
24
12
12
24
TFA, 20 °C
0
22
35
40b
82
79
72
t
OEt
41
47
B
B
TFA, 0–20 °C
Me3SiOTf, –78 to 20 °C
150 °C
u
v
OEt
s
Me
H
Et 98
68
A
C
60c
t
w
x
p
r
Et
Me
H
Et 98
Et 97
70
A
TFA, 0–20 °C
Me3SiOTf, 0–20 °C
150 °C
u
Ph
82
79
72
A
B
C
a Yields of isolated products.
b Besides, 4a¢ was formed, see footnote in Table 2.
v
y
z
s
t
2-MeOC6H4
2-ClC6H4
H
H
Me 50
Me 53
79
63
B
B
w
a Yields of isolated products.
The application of method C gave 4o in 60% yield; be-
sides, a small amount of pyrrole 4o¢ was isolated (5%).
The cyclization of 3w, derived from heptane-3,5-dione
(1t), gave 4p in good yield when method A was applied.
The TFA-mediated cyclization of 3x, prepared from ben-
zoylacetone (1u), afforded the 3-benzoylpyrrole 4r in
82% yield (method A). The use of Me3SiOTf (0–20 °C,
method B) and heating of 3m in DMSO (method C) also
proved to be successful (Table 2, footnote e). However,
b Besides, 4a¢ was isolated in 19% yield (Figure 1).
c Besides, 4o¢ was isolated in 5% yield (Figure 1).
d Failed.
e Conditions: method A: TFA (10 equiv), CH2Cl2, 0–20 °C, 12 h;
method B: Me3SiOTf (1 equiv), CH2Cl2, –78 to 20 °C (for b-keto
esters) or 0–20 °C (for 1,3-diketones), 12 h; method C: DMSO,
150 °C, 24 h.
Synthesis 2009, No. 2, 227–242 © Thieme Stuttgart · New York

PAPER
Staudinger–Aza-Wittig Reactions of 1,3-Dicarbonyl Compounds
229
slightly lower yields were obtained. Pyrroles 4s and 4t
were prepared in good yields starting from substituted
benzophenones 1v and 1w, respectively. Method B seems
to be the most general procedure to induce the cyclization
step. For aliphatic 1,3-diketones (1s,t) the application of
method A gave best results. For benzoylacetone deriva-
tives (1u–w) all three methods gave satisfactory results.
OEt
OEt
O
2a
Ph3P, THF
N
reflux, 8 h
O
8
9 (93%)
Scheme 3 Synthesis of 1-(2,2-diethoxyethyl)-2,5-dimethyl-1H-
pyrrole (9)
O
O
The Ph3P-mediated reaction of benzoylacetone (1u) with
1,1-diethoxy-3-azido-propane (10), available by reaction
of 1-chloro-3,3-diethoxypropane with sodium azide, gave
product 11. The TFA-mediated cyclization of the latter af-
forded pyridine 12 in excellent yield (Scheme 4).
EtO
EtO
N
N
OEt
OMe
OEt
4a'
4o'
Figure 1 Structures of 4a¢ and 4o¢
O
O
OEt
OEt
Enamines 6a–d were prepared by reaction of 2a with cy-
clohexane-1,3-diones 5a–d (Scheme 2, Table 3). Treat-
ment of 6a–d with TFA afforded 6,7-dihydro-1H-indol-
4(5H)-ones 7a–d in very good yields (method A). Com-
pound 7a12 was also successfully prepared, albeit in lower
yield, by application of method C.
Ph
O
HN
1u
i
Ph
+
OEt
11 (95%)
N3
OEt
10
ii
OEt
OEt
OEt
N
O
HN
N3
OEt
Ph
2a
R1
R2
R1
R2
O
O
i
O
12 (96%)
5a–d
6a–d
Scheme 4 Synthesis of 12; Reagents and conditions: i: Ph3P, THF,
reflux, 8 h; ii: TFA (10 equiv), CH2Cl2, 0–20 °C, 12 h.
HN
ii
In conclusion, a variety of pyrroles and 1,5,6,7-tetrahy-
dro-4H-indol-4-ones were prepared by condensation of
1,3-dicarbonyl compounds with 2-azido-1,1-diethoxy-
ethane and subsequent cyclization. The best conditions for
the cyclization step (acid, Lewis acid or heating) depend
on the substitution pattern of the intermediate. The strate-
gy could be successfully applied to the synthesis of a func-
tionalized pyridine.
R1
R2
O
7a–d
Scheme 2 Synthesis of 1,5,6,7-tetrahydro-4H-indol-4-ones 7a–d;
Reagents and conditions: i: Ph3P, THF, reflux, 8 h; ii: method A: TFA
(10 equiv), CH2Cl2, 0–20 °C, 12 h; method C: DMSO, 150 °C, 24 h.
Table 3 Yields of Enamines 6 and 1,5,6,7-Tetrahydro-4H-indol-4-
ones 7
All moisture-free solvents (>99.9 grade) were used as purchased
and all reactions were carried out under Argon atmosphere. For 1H
and 13C NMR spectra the deuterated solvents indicated were used.
Mass spectrometric data (MS) were obtained by electron ionization
(EI, 70 eV), chemical ionization (CI, H2O) or electrospray ioniza-
tion (ESI). For preparative scale chromatography, silica gel (60–
200 mesh) was used. Melting points are uncorrected.
6, 7
R1
R2
Yield (%) Yield (%) Method
(6)a
(7)a
a
H
H
97
95
71
A
C
b
c
Me
Me
Ph
Me
H
92
94
92
60
75
73
A
A
A
CAUTION: The handling of low-molecular weight azides is dan-
gerous due to their potentially explosive character. Although, in our
hands, neat 2a,b and 8 did not appear to be shock-sensitive, the
compounds should be handled with great care. Neat azides must not
be heated or distilled and all reactions should be carried out on small
scale. The use of a safety shield is highly recommended.
d
H
a Yields of isolated products.
2-Azido-1,1-diethoxyethane (2a)
The Ph3P-mediated reaction of hexane-2,5-dione (8) with
2a afforded pyrrole 9 in excellent yield by Staudinger–
aza-Wittig reaction and subsequent cyclization
(Scheme 3).
Starting with 2-bromo-1,1-diethoxyethane (31 mL, 200 mmol), so-
dium azide (19.50 g, 300 mmol) and potassium iodide (3.32 g, 20
mmol) in DMSO (150 mL), 2b was isolated without further purifi-
cation as a colorless oil (30.629 g, 96%).
Synthesis 2009, No. 2, 227–242 © Thieme Stuttgart · New York

230
E. Bellur et al.
PAPER
IR (neat): 2980 (s), 2932 (m), 2884 (m), 2104 (s, N3), 1479 (w),
1446 (w), 1376 (w), 1348 (w), 1273 (s), 1233 (w), 1130 (s), 1067
(s), 946 (w), 921 (w), 844 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 1.25 (t, J = 7.2 Hz, 6 H, 2 × CH3),
3.25 (d, J = 5.4 Hz, 2 H, CH2N3), 3.54–3.64 (m, 2 H, OCH2), 3.68–
3.78 (m, 2 H, OCH2), 4.61 (t, J = 5.4 Hz, 1 H, OCH).
Ethyl 3-[(2,2-Diethoxyethyl)amino]but-2-enoate (3b)
Starting with ethyl acetoacetate (1b) (0.4 mL, 3.0 mmol), 2-azido-
1,1-diethoxyethane (2a) (0.573 g, 3.6 mmol) and Ph3P (1.180 g, 4.5
mmol) in THF (15 mL), 3b was isolated after chromatography (sil-
ica gel, n-hexane–EtOAc, 100:1 → 5:1) as a colorless oil (0.656 g,
89%).
IR (neat): 3289 (w), 2980 (s), 2932 (m), 2898 (m), 1741 (m), 1725
(m), 1656 (s), 1609 (s), 1502 (m), 1447 (s), 1381 (m), 1288 (s), 1240
(s), 1176 (s), 1136 (s), 1061 (s), 975 (w), 935 (w), 849 (w), 791 (s),
706 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 1.23 (t, J = 7.2 Hz, 6 H, 2 × CH3),
1.25 (t, J = 7.2 Hz, 3 H, CH3), 1.94 (s, 3 H, CH3), 3.33 (dd, J = 6.3,
5.4 Hz, 2 H, NCH2), 3.51–3.61 (m, 2 H, OCH2), 3.68–3.78 (m, 2 H,
OCH2), 4.09 (q, J = 7.2 Hz, 2 H, OCH2), 4.47 (s, 1 H, CH), 4.50 (t,
J = 5.4 Hz, 1 H, OCH), 8.61 (br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 13.9, 14.6 (2 C), 18.8 (CH3), 45.2
(NCH2), 57.3, 62.3 (2C, OCH), 82.4 (CH=C), 101.3 (OCH), 160.7
(N–C=CH), 169.5 (O=C–O).
MS (EI, 70 eV): m/z (%) = 245 (M+, 14), 200 (21), 154 (6), 126 (7),
103 (100), 96 (34), 88 (12), 75 (64).
13C NMR (CDCl3, 75 MHz): d = 15.0 (2 C, CH3), 52.2 (CH2N3),
62.7 (2 C, OCH2), 101.21 (OCH).
MS (EI, 70 eV): m/z (%) = 160 (M+, 100), 145 (31), 114 (17), 91
(24).
2-Azido-1,1-dimethoxyethane (2b)
Sodium azide (19.503 g, 300 mmol) and potassium iodide (3.32 g,
20 mmol) were added to 1-bromo-2,2-dimethoxyethane (824 mL,
200 mmol) in DMSO (140 mL) at r.t. The reaction mixture was
heated to 90 °C and stirred for 5 d at 90 °C. After cooling to r.t., H2O
(200 mL) and Et2O (200 mL) were added, the organic layer was sep-
arated and the aqueous layer was repeatedly extracted with Et2O
(4 × 200 mL). The combined organic extracts were dried over
Na2SO4, filtered, and the filtrate was concentrated to dryness in
vacuo. Product 2a was isolated without further purification as a
slightly yellow oil (22.31 g, 85%).
HRMS (ESI): m/z calcd for C12H23NO4 [M+]: 245.16271; found:
245.16282.
IR (neat): 2995 (w), 2939 (m), 2837 (w, C–H), 2102 (s, N3), 1444
(m), 1311 (w), 1275 (s), 1196 (m), 1129 (s), 1089 (s), 1064 (s), 1035
(m), 979 (w), 922 cm-1 (w).
1H NMR (CDCl3, 300 MHz): d = 3.27 (d, J = 5.3 Hz, 2 H, CH2N3),
3.43 (s, 6 H, 2 × OCH3), 4.48 (t, J = 5.3 Hz, 1 H, CH).
13C NMR (CDCl3, 75 MHz): d = 51.66 (CH2N3), 54.25 (2 C,
OCH3), 103.08 (CH).
Isopropyl 3-[(2,2-Diethoxyethyl)amino]but-2-enoate (3c)
Starting with isopropyl acetoacetate (1c) (0.44 mL, 3.0 mmol), 2-
azido-1,1-diethoxyethane (2a) (0.573 g, 3.6 mmol) and Ph3P (1.180
g, 4.5 mmol) in THF (15 mL), 3c was isolated after chromatography
(silica gel, n-hexane–EtOAc, 100:1 → 3:1) as a colorless oil (0.673
g, 87%).
IR (neat): 3288 (w), 2980 (s), 2932 (s), 2882 (m), 1651 (s), 1608 (s),
1502 (m), 1451 (s), 1377 (s), 1284 (s), 1241 (s), 1176 (s), 1140 (s),
1113 (s), 1067 (s), 993 (m), 948 (w), 790 (m), 705 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 1.21 (d, J = 6.0 Hz, 6 H, 2 × CH3),
1.25 (t, J = 7.2 Hz, 6 H, 2 × CH3), 1.93 (s, 3 H, CH3), 3.33 (dd,
J = 6.3, 5.7 Hz, 2 H, NCH2), 3.51–3.61 (m, 2 H, OCH2), 3.68–3.78
(m, 2 H, OCH2), 4.44 (s, 1 H, CH=C), 4.50 (t, J = 5.7 Hz, 1 H,
OCH), 4.99 (sept, J = 6.0 Hz, 1 H, OCH), 8.63 (br s, 1 H, NH).
MS (EI, 70 eV): m/z (%) = 75 ([M – CH2N3]+, 100).
Synthesis of Enamines 3; Typical Procedure
Synthesis of 3-[(2,2-Diethoxyethyl)amino]-1-phenylbut-2-en-1-
one (3x)
To benzoylacetone (0.200 g, 1.2 mmol) and 2-azido-1,1-diethoxy-
ethane (2) (0.236 g, 1.5 mmol) in THF (10 mL) was added Ph3P
(0.656 g, 2.5 mmol) at 20 °C. The reaction mixture was heated and
stirred for 8 h at reflux. After cooling to 20 °C, the solvent was re-
moved in vacuo and the residue was purified by column chromatog-
raphy (silica gel, n-hexane–EtOAc, 100:1 → 1:1) to give 3x as a
lightly yellow oil (0.322 g, 97%).
13C NMR (CDCl3, 75 MHz): d = 14.8 (2 C), 19.1, 21.7 (2 C, CH3),
45.5 (NCH2), 62.6 (2 C, OCH2), 64.3 (OCH), 83.2 (CH=C), 101.6
(OCH), 160.8 (N–C=CH), 169.4 (O=C–O).
MS (EI, 70 eV): m/z (%) = 259 (M+, 7), 214 (6), 200 (9), 172 (3),
154 (3), 126 (8), 113 (13), 103 (100), 96 (31), 85 (16), 75 (65).
HRMS (ESI): m/z calcd for C13H25NO4 [M+]: 259.17836; found:
259.17861.
Methyl 3-[(2,2-Diethoxyethyl)amino]but-2-enoate (3a)
Starting with methyl acetoacetate (1a) (0.19 mL, 1.72 mmol), 2-azi-
do-1,1-diethoxyethane (2a) (0.329 g, 2.1 mmol) and Ph3P (0.677 g,
2.6 mmol) in THF (10 mL), 3a was isolated after chromatography
(silica gel, n-hexane–EtOAc, 100:1 → 1:1) as a colorless oil (0.333
g, 86%).
Isobutyl 3-[(2,2-Diethoxyethyl)amino]but-2-enoate (3d)
Starting with isobutyl acetoacetate (1d) (0.48 mL, 3.0 mmol), 2-azi-
do-1,1-diethoxyethane (2a) (0.573 g, 3.6 mmol) and Ph3P (1.180 g,
4.5 mmol) in THF (15 mL), 3d was isolated after chromatography
(silica gel, n-hexane–EtOAc, 100:1 → 5:1) as a colorless oil (0.723
g, 88%).
IR (neat): 3291 (w), 2978 (m), 2884 (w), 1658 (s), 1608 (s), 1504
(m), 1443 (m), 1382 (m), 1352 (w), 1291 (s), 1239 (s), 1177 (s),
1136 (s), 1058 (s), 787 (m), 703 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 1.23 (t, J = 7.2 Hz, 6 H, 2 × CH3),
1.94 (s, 3 H, CH3), 3.33 (dd, J = 6.3, 5.4 Hz, 2 H, NCH2), 3.51–3.61
(m, 2 H, OCH2), 3.62 (s, 3 H, OCH3), 3.68–3.76 (m, 2 H, OCH2),
4.48 (d, J = 2.7 Hz, 1 H, CH=C), 4.51 (d, J = 5.4 Hz, 1 H, OCH),
8.61 (br s, 1 H, NH).
IR (neat): 3289 (w), 2970 (m), 2933 (m), 2880 (m), 1725 (m), 1655
(s), 1609 (s), 1542 (w), 1501 (m), 1449 (s), 1381 (m), 1285 (s), 1239
(s), 1173 (s), 1135 (s), 1057 (s), 967 (w), 937 (w), 790 (m), 704
cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 0.92 (d, J = 6.9 Hz, 6 H, 2 × CH3),
1.22 (t, J = 7.2 Hz, 6 H, 2 × CH3), 1.92 (m, J = 6.9 Hz, 1 H, CH),
1.94 (s, 3 H, CH3), 3.32 (dd, J = 6.0, 5.7 Hz, 2 H, NCH2), 3.50–3.60
(m, 2 H, OCH2), 3.70–3.79 (m, 2 H, OCH2), 3.80 (d, J = 6.9 Hz, 2
H, OCH2), 4.48 (s, 1 H, CH), 4.50 (t, J = 5.7 Hz, 1 H, OCH), 8.61
(br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 15.2 (2 C), 19.6 (CH3), 46.0
(NCH2), 49.8 (OCH3), 63.1 (2 C, OCH2), 82.6 (CH=C), 102.0
(OCH), 161.6 (N–C=CH), 170.6 (O=C–O).
MS (EI, 70 eV): m/z (%) = 231 (M+, 11), 200 (5), 186 (11), 140 (4),
128 (5), 103 (100), 96 (25), 84 (11), 75 (70).
Anal. Calcd for C11H21NO4 (231.292): C, 57.12; H, 9.15. Found: C,
56.94; H, 9.23.
Synthesis 2009, No. 2, 227–242 © Thieme Stuttgart · New York

PAPER
Staudinger–Aza-Wittig Reactions of 1,3-Dicarbonyl Compounds
231
13C NMR (CDCl3, 75 MHz): d = 14.9 (2 C), 18.8 (2 C), 19.1 (CH3),
27.6 (CH), 45.6 (NCH2), 62.7 (2C), 68.2 (OCH2), 82.7 (CH=C),
101.6 (OCH), 161.0 (N–C=CH), 170.0 (O=C–O).
MS (EI, 70 eV): m/z (%) = 273 (M+, 6), 228 (4), 200 (5), 126 (3),
113 (5), 103 (100), 96 (11), 85 (16), 75 (44).
HRMS (ESI): m/z calcd for C14H27NO4 [M+]: 273.19401; found:
273.19403.
1H NMR (CDCl3, 300 MHz): d = 1.23 (t, J = 7.2 Hz, 6 H, 2 × CH3),
1.95 (s, 3 H, CH3), 3.33 (dd, J = 6.3, 5.4 Hz, 2 H, NCH2), 3.50–3.60
(m, 2 H, OCH2), 3.68–3.78 (m, 2 H, OCH2), 4.50 (t, J = 5.4 Hz, 1
H, OCH), 4.52 (s, 1 H, CH=C), 4.55 (dt, J = 5.4, 1.5 Hz, 2 H,
OCH2), 5.18 (dq, J = 10.5, 1.5 Hz, 1 H, CH2=CH), 5.29 (dq,
J = 17.4, 1.5 Hz, 1 H, CH2=CH), 5.88–6.01 (m, 1 H, CH=CH2), 8.61
(br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 14.7 (2 C), 19.0 (CH3), 45.4
(NCH2), 62.46, 62.48 (2 C, OCH2), 82.2 (CH=C), 101.4 (OCH),
116.1 (CH2=CH), 133.2 (CH=CH2), 161.3 (N–C=CH), 169.2
(O=C–O).
MS (EI, 70 eV): m/z (%) = 257 (M+, 6), 212 (11), 200 (5), 154 (7),
126 (4), 111 (2), 103 (100), 96 (17), 84 (100), 75 (64).
tert-Butyl 3-[(2,2-Diethoxyethyl)amino]but-2-enoate (3e)
Starting with tert-butyl acetoacetate (1e) (0.33 mL, 2.0 mmol), 2-
azido-1,1-diethoxyethane (2a) (0.382 g, 2.4 mmol) and Ph3P (0.787
g, 3.0 mmol) in THF (10 mL), 3e was isolated after chromatography
(silica gel, n-hexane–EtOAc, 100:1 → 5:1) as a colorless oil (0.341
g, 62%).
HRMS (ESI): m/z calcd for C13H23NO4 [M+]: 257.16271; found:
IR (neat): 2976 (w), 2927 (w), 1722 (w), 1651 (s), 1610 (s), 1498
(w), 1449 (w), 1369 (w), 1292 (m), 1244 (m), 1141 (s), 1068 (m),
986 (w), 791 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 1.25 (t, J = 7.2 Hz, 6 H, 2 × CH3),
1.47 (s, 9 H, t-Bu), 1.91 (s, 3 H, CH3), 3.30 (dd, J = 6.6, 5.7 Hz, 2
H, NCH2), 3.50–3.60 (m, 2 H, OCH2), 3.68–3.78 (m, 2 H, OCH2),
4.40 (s, 1 H, CH), 4.49 (t, J = 5.7 Hz, 1 H, OCH), 8.59 (br s, 1 H,
NH).
257.16325.
Methyl 3-[(2,2-Diethoxyethyl)amino]pent-2-enoate (3h)
Starting with methyl propionylacetate (1h) (0.38 mL, 3.0 mmol), 2-
azido-1,1-diethoxyethane (2a) (0.573 g, 3.6 mmol) and Ph3P (1.180
g, 4.5 mmol) in THF (15 mL), 3h was isolated after chromatogra-
phy (silica gel, n-hexane–EtOAc, 100:1 → 5:1) as a slightly light
yellow oil (0.604 g, 82%).
IR (neat): 3288 (w), 2978 (w), 2932 (w), 1658 (s), 1606 (s), 1501
(m), 1444 (s), 1383 (m), 1324 (w), 1280 (m), 1236 (s), 1177 (s),
1136 (s), 1063 (s), 792 cm–1 (m).
1H NMR (CDCl3, 300 MHz): d = 1.15 (t, J = 7.5 Hz, 3 H, CH3),
1.23 (t, J = 7.2 Hz, 6 H, 2 × CH3), 2.25 (q, J = 7.5 Hz, 2 H, CH2),
3.33 (dd, J = 6.0, 5.7 Hz, 2 H, NCH2), 3.54–3.64 (m, 2 H, OCH2),
3.63 (s, 3 H, OCH3), 3.68–3.79 (m, 2 H, OCH2), 4.50 (s, 1 H,
CH=C), 4.52 (t, J = 5.7 Hz, 1 H, OCH), 8.61 (br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 15.0 (2 C), 19.2, 28.3 (3 C,
3 × CH3), 45.6 (NCH2), 62.9 (2 C, OCH2), 81.4 (C), 84.6 (CH=C),
101.9 (OCH), 160.4 (N–C=CH), 170.0 (O=C–O).
MS (EI, 70 eV): m/z (%) = 273 (M+, 100), 246 (1), 229 (5), 200 (96).
HRMS (EI, 70 eV): m/z calcd for C14H27NO4 [M+]: 273.19400;
found: 273.19415.
2-Methoxyethyl 3-[(2,2-Diethoxyethyl)amino]but-2-enoate (3f)
Starting with 2-methoxyethyl acetoacetate (1f) (0.495 g, 3.0 mmol),
2-azido-1,1-diethoxyethane (2a) (0.573 g, 3.6 mmol) and Ph3P
(1.180 g, 4.5 mmol) in THF (15 mL), 3f was isolated after chroma-
tography (silica gel, n-hexane–EtOAc, 100:1 → 3:1) as a colorless
oil (0.736 g, 89%).
13C NMR (CDCl3, 75 MHz): d = 11.7, 14.8 (2 C, CH3), 25.0 (CH2),
44.9 (NCH2), 49.3 (OCH3), 62.5 (2 × OCH2), 80.3 (CH=C), 101.4
(OCH), 166.1 (N–C=CH), 170.4 (O=C–O).
MS (EI, 70 eV): m/z (%) = 245 (M+, 13), 214 (5), 200 (12), 142 (7),
130 (6), 109 (32), 103 (100), 75 (68).
IR (neat): 3292 (w), 2978 (s), 2932 (s), 2885 (s), 1743 (m), 1722
(m), 1655 (s), 1603 (s), 1503 (s), 1448 (s), 1381 (s), 1290 (s), 1241
(s), 1169 (s), 1121 (s), 1064 (s), 978 (m), 938 (w), 849 (m), 787 (s),
705 (m), 554 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 1.24 (t, J = 7.2 Hz, 6 H, 2 × CH3),
1.93 (s, 3 H, CH3), 3.33 (dd, J = 6.6, 5.7 Hz, 2 H, NCH2), 3.39 (s, 3
H, OCH3), 3.50–3.63 (m, 4 H, 2 × OCH2), 3.68–3.78 (m, 2 H,
OCH2), 4.18–4.21 (m, 2 H, OCH2), 4.52 (t, J = 5.7 Hz, 1 H, OCH),
4.54 (s, 1 H, CH), 8.61 (br s, 1 H, NH).
Anal. Calcd for C12H23NO4 (245.315): C, 58.75; H, 9.45. Found: C,
58.37; H, 9.41.
Ethyl 3-[(2,2-Diethoxyethyl)amino]hex-2-enoate (3i)
Starting with ethyl 3-oxohexanoate (1i) (0.500 g, 3.2 mmol), 2-azi-
do-1,1-diethoxyethane (2a) (0.605 g, 3.8 mmol) and Ph3P (1.243 g,
4.7 mmol) in THF (17 mL), 3i was isolated after chromatography
(silica gel, n-hexane–EtOAc, 100:1 → 10:1) as a slightly light yel-
low oil (0.657 g, 75%).
IR (neat): 3283 (w), 2974 (m), 2932 (w), 2878 (w), 1654 (s), 1607
(s), 1501 (w), 1452 (m), 1378 (w), 1296 (m), 1264 (m), 1234 (s),
1175 (s), 1135 (s), 1061 (s), 792 cm–1 (m).
13C NMR (CDCl3, 75 MHz): d = 14.5 (2 C), 19.0 (CH3), 45.4
(NCH2), 58.3 (OCH3), 60.9, 62.5 (2 C), 70.5 (OCH2), 82.3 (CH=C),
101.4 (OCH), 161.3 (N–C=CH), 169.4 (O=C–O).
1H NMR (CDCl3, 300 MHz): d = 0.97 (t, J = 7.2 Hz, 3 H, CH3),
1.22 (t, J = 7.2 Hz, 6 H, 2 × CH3), 1.26 (t, J = 7.2 Hz, 3 H, CH3),
1.55 (sext, J = 7.8 Hz, 2 H, CH2), 2.17 (t, J = 7.8 Hz, 2 H, CH2),
3.32 (dd, J = 6.0, 5.7 Hz, 2 H, NCH2), 3.52–3.62 (m, 2 H, OCH2),
3.68–3.78 (m, 2 H, OCH2), 4.09 (q, J = 7.2 Hz, 2 H, OCH2), 4.47 (s,
1 H, CH), 4.51 (t, J = 5.7 Hz, 1 H, OCH), 8.62 (br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 13.4, 14.2, 14.9 (2 C, CH3), 20.8,
34.1 (CH2), 45.2 (NCH2), 57.8, 62.6 (2 C, OCH2), 81.9 (CH=C),
101.5 (OCH), 164.6 (N–C=CH), 170.1 (O=C–O).
MS (EI, 70 eV): m/z (%) = 275 (M+, 5), 259 (1), 230 (2), 200 (6),
154 (10), 126 (5), 103 (100), 96 (14), 75 (60).
Anal. Calcd for C13H25NO5 (275.341): C, 56.71; H, 9.15. Found: C,
56.53; H, 9.43.
Allyl 3-[(2,2-Diethoxyethyl)amino]but-2-enoate (3g)
Starting with allyl acetoacetate (1g) (0.41 mL, 3.0 mmol), 2-azido-
1,1-diethoxyethane (2a) (0.573 g, 3.6 mmol) and Ph3P (1.180 g, 4.5
mmol) in THF (15 mL), 3g was isolated after chromatography (sil-
ica gel, n-hexane–EtOAc, 100:1 → 3:1) as a colorless oil (0.695 g,
90%).
MS (EI, 70 eV): m/z (%) = 273 (M+, 5), 228 (10), 200 (1), 182 (3),
170 (2), 154 (5), 124 (11), 109 (3), 103 (100), 96 (6), 84 (6), 75 (61).
IR (neat): 3291 (w), 2978 (s), 2931 (m), 2884 (m), 1665 (s), 1606
(s), 1503 (m), 1446 (m), 1381 (m), 1359 (m), 1286 (s), 1238 (s),
1169 (s), 1130 (s), 1058 (s), 1000 (m), 931 (m), 787 (m), 705 cm–1
(w).
HRMS (ESI): m/z calcd for C14H27NO4 [M+]: 273.19400; found:
273.19426.
Synthesis 2009, No. 2, 227–242 © Thieme Stuttgart · New York

232
E. Bellur et al.
PAPER
tert-Butyl 3-[(2,2-Diethoxyethyl)amino]hept-2-enoate (3j)
Starting with tert-butyl 3-oxoheptanoate (1j) (0.401 g, 2.0 mmol),
2-azido-1,1-diethoxyethane (2a) (0.382 g, 2.4 mmol), and Ph3P
(0.787 g, 3.0 mmol) in THF (10 mL), 3j was isolated after chroma-
tography (silica gel, n-hexane–EtOAc, 100:1 → 5:1) as a colorless
oil (0.490 g, 78%).
J = 7.2 Hz, 2 H, OCH2), 4.47 (s, 1 H, CH), 4.51 (t, J = 5.7 Hz, 1 H,
OCH), 8.65 (br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 13.6, 14.2, 14.9 (2 C, CH3), 22.2,
27.6, 28.7, 29.0, 31.3, 32.2 (CH2), 45.3 (NCH2), 57.8, 62.6 (2 C,
OCH2), 81.9 (CH=C), 101.6 (OCH), 164.9 (N–C=CH), 170.1
(O=C–O).
IR (neat): 2970 (s), 2934 (s), 2874 (m), 1736 (s), 1719 (s), 1649 (s),
1608 (s), 1459 (m), 1370 (m), 1314 (m), 1285 (m), 1247 (s), 1147
(s), 1068 (m), 1014 (w), 844 (w), 793 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 0.91 (t, J = 7.2 Hz, 3 H, CH3),
1.23 (t, J = 7.2 Hz, 6 H, 2 × CH3), 1.29–1.36 (m, 2 H, CH2), 1.47 (s,
9 H, t-Bu), 1.58 (quint, J = 7.2 Hz, 2 H, CH2), 2.18 (t, J = 7.2 Hz, 2
H, CH2), 3.30 (dd, J = 6.1, 5.4 Hz, 2 H, NCH2), 3.51–3.61 (m, 2 H,
OCH2), 3.68–3.78 (m, 2 H, OCH2), 4.41 (s, 1 H, CH), 4.51 (t,
J = 5.4 Hz, 1 H, OCH), 8.61 (br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 13.3, 14.8 (2 C, CH3), 21.7, 25.1
(CH2), 28.1 (3 × CH3), 29.7 (CH2), 45.2 (NCH2), 62.6 (2 × OCH2),
81.0 (C), 83.6 (CH=C), 101.7 (OCH), 164.1 (N–C=CH), 170.1
(O=C–O).
MS (EI, 70 eV): m/z (%) = 329 (M+, 4), 284 (8), 226 (5), 143 (6),
130 (25), 103 (100), 75 (45).
Anal. Calcd for C18H35NO4 (329.475): C, 65.62; H, 10.71. Found:
C, 65.88; H, 10.42.
Ethyl 3-[(2,2-Diethoxyethyl)amino]dodec-2-enoate (3m)
Starting with ethyl 3-oxododecanoate (1l) (0,485 g, 2.0 mmol), 2-
azido-1,1-diethoxyethane (2a) (0.382 g, 2.4 mmol) and Ph3P (0.787
g, 3.0 mmol) in THF (10 mL), 3m was isolated after chromatogra-
phy (silica gel, n-hexane–EtOAc, 100:1 → 10:1) as a slightly light
yellow oil (0.612 g, 86%).
IR (neat): 3280 (w), 2970 (s), 2927 (s), 2860 (s), 1654 (s), 1607 (s),
1501 (m), 1458 (m), 1376 (m), 1284 (s), 1234 (s), 1173 (s), 1134 (s),
1060 (s), 790 (m), 713 cm–1 (w).
MS (EI, 70 eV): m/z (%) = 315 (M+, 4), 242 (4), 214 (4), 156 (4),
138 (4), 124 (4), 103 (100), 85 (11), 75 (41).
HRMS (ESI): m/z calcd for C17H33NO4 [M+]: 315.24097; found:
315.24059.
1H NMR (CDCl3, 300 MHz): d = 0.88 (t, J = 6.9 Hz, 3 H, CH3),
1.15–1.33 (m, 21 H, 3 × CH3, 6 × CH2), 1.50 (quint, J = 7.5 Hz, 2
H, CH2), 2.18 (t, J = 7.5 Hz, 2 H, CH2), 3.32 (dd, J = 6.0, 5.7 Hz, 2
H, NCH2), 3.52–3.62 (m, 2 H, OCH2), 3.68–3.78 (m, 2 H, OCH2),
4.09 (q, J = 7.2 Hz, 2 H, OCH2), 4.47 (s, 1 H, CH), 4.51 (t, J = 5.7
Hz, 1 H, OCH), 8.62 (br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 13.9, 14.4, 15.1 (2 C, CH3), 22.5,
27.8, 29.1, 29.2, 29.3, 29.4, 31.7, 32.4 (CH2), 45.5 (NCH2), 58.1,
62.9 (2 C, OCH2), 82.0 (CH=C), 101.8 (OCH), 165.2 (N–C=CH),
170.4 (O=C–O).
Ethyl 3-[(2,2-Dimethoxyethyl)amino]dec-2-enoate (3k)
Starting with ethyl 3-oxodecanoate (1k) (0.257 g, 1.2 mmol), 2-azi-
do-1,1-dimethoxyethane (2b) (0.189 g, 1.4 mmol) and Ph3P (0.472
g, 1.8 mmol) in THF (8 mL), 3k was isolated after chromatography
(silica gel, n-hexane–EtOAc, 100:1 → 3:1) as a slightly light yellow
oil (0.321 g, 89%).
IR (neat): 3282 (m), 2929 (s), 2861 (s), 1653 (s), 1605 (s), 1501 (s),
1456 (s), 1372 (s), 1290 (s), 1241 (s), 1182 (s), 1135 (s), 1079 (s),
1054 (s), 981 (s), 925 (w), 896 (w), 831 (w), 789 (s), 712 (m), 664
cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 0.88 (t, J = 6.9 Hz, 3 H, CH3),
1.25 (t, J = 7.2 Hz, 3 H, CH3), 1.26–1.34 (m, 8 H, 4 × CH2), 1.51
(quint, J = 7.5 Hz, 2 H, CH2), 2.17 (t, J = 7.8 Hz, 2 H, CH2), 3.32
(dd, J = 6.0, 5.4 Hz, 2 H, NCH2), 3.42 (s, 6 H, 2 × OCH3), 4.09 (q,
J = 7.2 Hz, 2 H, OCH2), 4.41 (t, J = 5.4 Hz, 1 H, OCH), 4.48 (s, 1
H, CH), 8.61 (br s, 1 H, NH).
MS (EI, 70 eV): m/z (%) = 357 (M+, 1), 312 (2), 254 (2), 212 (5),
200 (4), 154 (5), 126 (3), 103 (100), 96 (12), 75 (55).
Anal. Calcd for C20H39NO4 (357.528): C, 67.19; H, 10.99. Found:
C, 67.24; H, 10.98.
tert-Butyl 3-[(2,2-Diethoxyethyl)amino]dodec-2-enoate (3n)
Starting with tert-butyl 3-oxododecanoate (1m) (0.200 g, 0.7
mmol), 2-azido-1,1-diethoxyethane (2a) (0.142 g, 0.9 mmol) and
Ph3P (0.291 g, 1.1 mmol) in THF (10 mL), 3n was isolated after
chromatography (silica gel, n-hexane–EtOAc, 100:1 → 5:1) as a
slightly light yellow oil (0.250 g, 88%).
13C NMR (CDCl3, 75 MHz): d = 13.8, 14.3 (CH3), 22.3, 27.7, 28.8,
29.1, 31.4, 32.3 (CH2), 44.4 (CH2), 54.0 (2 C, OCH3), 58.0 (OCH2),
82.1 (CH=C), 103.2 (OCH), 165.0 (N–C=CH), 170.4 (O=C–O).
IR (neat): 3278 (w), 2970 (s), 2927 (s), 2859 (s), 1650 (s), 1607 (s),
1496 (m), 1458 (m), 1370 (m), 1288 (s), 1241 (s), 1140 (s), 1068 (s),
1013 (m), 949 (w), 848 (w), 791 (m), 714 cm–1 (w).
MS (EI, 70 eV): m/z (%) = 301 (M+, 8), 270 (5), 256 (4), 226 (20),
180 (13), 88 (28), 75 (100).
1H NMR (CDCl3, 300 MHz): d = 0.88 (t, J = 6.9 Hz, 3 H, CH3),
1.23 (t, J = 7.2 Hz, 6 H, 2 × CH3), 1.23–1.39 (m, 14 H, 7 × CH2),
1.46 (s, 9 H, 3 × CH3), 2.15 (t, J = 7.8 Hz, 2 H, CH2), 3.30 (dd,
J = 6.0, 5.7 Hz, 2 H, NCH2), 3.50–3.60 (m, 2 H, OCH2), 3.68–3.78
(m, 2 H, OCH2), 4.40 (s, 1 H, CH), 4.50 (t, J = 5.7 Hz, 1 H, OCH),
8.61 (br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 13.9, 15.1 (2 C, CH3), 22.5, 27.9
(CH2), 28.4 (3 × CH3), 29.1, 29.2, 29.3, 31.7, 32.4, 42.7 (CH2), 45.4
(NCH2), 62.9 (2 × OCH2), 81.5 (C), 83.8 (CH = C), 102.0 (OCH),
164.5 (N–C=CH), 170.5 (O=C–O).
Anal. Calcd for C16H31NO4 (301.426): C, 63.76; H, 10.37. Found:
C, 63.91; H, 9.95.
Ethyl 3-[(2,2-Diethoxyethyl)amino]dec-2-enoate (3l)
Starting with ethyl 3-oxodecanoate (1k) (0.429 g, 2.0 mmol), 2-azi-
do-1,1-diethoxyethane (2a) (0.382 g, 2.4 mmol) and Ph3P (0.787 g,
3.0 mmol) in THF (10 mL), 3l was isolated after chromatography
(silica gel, n-hexane–EtOAc, 100:1 → 10:1) as a slightly light yel-
low oil (0.555 g, 84%).
IR (neat): 3280 (w), 2973 (s), 2928 (s), 2863 (s), 1655 (s), 1606 (s),
1501 (m), 1457 (m), 1376 (m), 1283 (s), 1233 (s), 1173 (s), 1135 (s),
1059 (s), 789 (m), 712 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 0.88 (t, J = 7.2 Hz, 3 H, CH3),
1.24 (t, J = 7.2 Hz, 6 H, 2 × CH3), 1.26 (t, J = 7.2 Hz, 3 H, CH3),
1.20–1.33 (m, 8 H, 4 × CH2), 1.51 (quint, J = 7.8 Hz, 2 H, CH2),
2.19 (t, J = 7.8 Hz, 2 H, CH2), 3.32 (dd, J = 6.0, 5.7 Hz, 2 H, NCH2),
3.51–3.61 (m, 2 H, OCH2), 3.68–3.78 (m, 2 H, OCH2), 4.09 (q,
MS (EI, 70 eV): m/z (%) = 385 (M+, 4), 312 (1), 282 (2), 226 (8),
214 (31), 197 (27), 155 (60), 114 (12), 103 (100), 75 (31).
HRMS (ESI): m/z calcd for C22H43NO4 [M+]: 385.3187; found:
385.3178.
Ethyl 3-[(2,2-Dimethoxyethyl)amino]tridec-2-enoate (3o)
Starting with ethyl 3-oxotridecanoate (1n) (0.141 g, 0.6 mmol), 2-
azido-1,1-dimethoxyethane (2b) (0.087 g, 0.7 mmol) and Ph3P
Synthesis 2009, No. 2, 227–242 © Thieme Stuttgart · New York

PAPER
Staudinger–Aza-Wittig Reactions of 1,3-Dicarbonyl Compounds
233
(0.216 g, 0.8 mmol) in THF (5 mL), 3o was isolated after chroma-
tography (silica gel, n-hexane–EtOAc, 100:1 → 3:1) as a light yel-
low oil (0.163 g, 86%).
13C NMR (CDCl3, 75 MHz): d = 14.0, 14.5 (CH3), 22.6, 23.4, 27.9,
28.9, 29.2, 29.3, 29.4, 29.5, 31.8, 32.5 (CH2), 44.6 (NCH2), 54.3 (2
C, OCH3), 58.2 (OCH2), 82.2 (CH=C), 103.4 (OCH), 165.3 (N–
=CH), 170.6 (O=C–O).
MS (EI, 70 eV): m/z (%) = 357 (M+, 3), 343 (4), 326 (1), 312 (6),
282 (13), 268 (15), 222 (5), 88 (29), 75 (100).
IR (neat): 3282 (w), 2928 (s), 2857 (s), 1655 (s), 1608 (s), 1501 (m),
1458 (m), 1372 (m), 1287 (m), 1242 (s), 1179 (s), 1135 (s), 1080 (s),
1056 (s), 981 (w), 790 (m), 713 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 0.88 (t, J = 6.9 Hz, 3 H, CH3),
1.25 (t, J = 7.2 Hz, 3 H, CH3), 1.26–1.33 (m, 14 H, 7 × CH2), 1.51
(quint, J = 7.5 Hz, 2 H, CH2), 2.17 (t, J = 7.8 Hz, 2 H, CH2), 3.32
(dd, J = 6.0, 5.7 Hz, 2 H, NCH2), 3.42 (s, 6 H, 2 × OCH3), 4.09 (q,
J = 7.2 Hz, 2 H, OCH2), 4.41 (t, J = 5.7 Hz, 1 H, OCH), 4.48 (s, 1
H, CH), 8.60 (br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 14.0, 14.5 (CH3), 22.6, 27.9, 29.20,
29.23, 29.3, 29.4, 29.5, 31.8, 32.5 (CH2), 44.5 (NCH2), 54.3 (2 C,
OCH3), 58.2 (OCH2), 82.2 (CH=C), 103.4 (OCH), 165.2 (N–
C=CH), 170.6 (O=C–O).
Anal. Calcd for C20H39NO4 (357.533): C, 67.19; H, 10.99. Found:
C, 67.39; H, 11.19.
Ethyl 3-[(2,2-Diethoxyethyl)amino]tetradec-2-enoate (3r)
Starting with ethyl 3-oxotetradecanoate (1o) (0.541 g, 2.0 mmol), 2-
azido-1,1-diethoxyethane (2a) (0.382 g, 2.4 mmol) and Ph3P (0.787
g, 3.0 mmol) in THF (10 mL), 3r was isolated after chromatography
(silica gel, n-hexane–EtOAc, 100:1 → 3:1) as a slightly light yellow
oil (0.703 g, 91%).
IR (neat): 3280 (w), 2926 (s), 2859 (s), 1700 (m), 1653 (s), 1607 (s),
1501 (m), 1458 (m), 1377 (m), 1283 (m), 1233 (s), 1172 (s), 1133
(s), 1059 (s), 789 (m), 715 cm–1 (w).
MS (EI, 70 eV): m/z (%) = 343 (M+, 6), 312 (3), 298 (3), 268 (26),
222 (8), 130 (42), 88 (36), 75 (100).
1H NMR (CDCl3, 300 MHz): d = 0.88 (t, J = 7.5 Hz, 3 H, CH3),
1.20–1.33 (m, 25 H, 3 × CH3, 8 × CH2), 1.48–1.59 (m, 2 H, CH2),
2.18 (t, J = 7.5 Hz, 2 H, CH2), 3.32 (dd, J = 6.0, 5.7 Hz, 2 H, NCH2),
3.50–3.60 (m, 2 H, OCH2), 3.68–3.78 (m, 2 H, OCH2), 4.09 (q,
J = 7.2 Hz, 2 H, OCH2), 4.47 (s, 1 H, CH=C), 4.51 (t, J = 5.7 Hz, 1
H, OCH), 8.62 (br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 13.7, 14.2, 14.9 (2 C, CH3), 22.3,
27.7, 29.01 (2 C), 29.03, 29.16, 29.28 (2 C), 31.6, 32.2 (CH2), 45.3
(NCH2), 57.8, 62.6 (2 C, OCH2), 81.9 (CH=C), 101.6 (OCH), 164.9
(N–C=CH), 170.1 (O=C–O).
HRMS (ESI): m/z calcd for C19H37NO4 [M+]: 343.2717; found:
343.2716.
Ethyl 3-[(2,2-Diethoxyethyl)amino]tridec-2-enoate (3p)
Starting with ethyl 3-oxotridecanoate (1n) (0.513 g, 2.0 mmol), 2-
azido-1,1-diethoxyethane (2a) (0.382 g, 2.4 mmol) and Ph3P (0.787
g, 3.0 mmol) in THF (10 mL), 3p was isolated after chromatogra-
phy (silica gel, n-hexane–EtOAc, 100:1 → 3:1) as a slightly light
yellow oil (0.678 g, 91%).
IR (neat): 3281 (w), 2926 (s), 2858 (m), 1698 (m), 1654 (s), 1607
(s), 1499 (m), 1456 (s), 1378 (m), 1282 (m), 1233 (s), 1174 (s), 1133
(s), 1059 (s), 790 (m), 714 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 0.88 (t, J = 7.2 Hz, 3 H, CH3),
1.16–1.32 (m, 23 H, 3 × CH3, 7 × CH2), 1.50 (quint, J = 7.5 Hz, 2
H, CH2), 2.18 (t, J = 7.5 Hz, 2 H, CH2), 3.32 (dd, J = 6.0, 5.7 Hz, 2
H, NCH2), 3.51–3.62 (m, 2 H, OCH2), 3.68–3.78 (m, 2 H, OCH2),
4.09 (q, J = 7.2 Hz, 2 H, OCH2), 4.47 (s, 1 H, CH = C), 4.51 (t,
J = 5.7 Hz, 1 H, OCH), 8.62 (br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 13.8, 14.3, 15.0 (2 C, CH3), 22.4,
27.7, 29.04, 29.09, 29.11, 29.22, 29.30, 31.6, 32.3 (CH2), 45.4
(NCH2), 57.9, 62.7 (2 C, OCH2), 82.0 (CH=C), 101.7 (OCH), 165.1
(N–C=CH), 170.3 (O=C–O).
MS (EI, 70 eV): m/z (%) = 385 (M+, 1), 340 (6), 326 82), 295 (22),
282 (6), 267 (2), 252 (2), 223 (2), 199 (6), 186 (6), 154 (7), 130 (8),
125 (6), 116 (5), 103 (100).
Anal. Calcd for C22H43NO4 (385.581): C, 68.53; H, 11.24. Found:
C, 68.58; H, 10.88.
Ethyl 7-Chloro-3-[(2,2-diethoxyethyl)amino]hept-2-enoate (3s)
Starting with ethyl 7-chloro-3-oxoheptanoate (1p) (0.413 g, 2.0
mmol), 2-azido-1,1-diethoxyethane (2a) (0.382 g, 2.4 mmol) and
Ph3P (0.787 g, 3.0 mmol) in THF (10 mL), 3s was isolated after
chromatography (silica gel, n-hexane–EtOAc, 100:1 → 5:1) as a
light yellow oil (0.537 g, 83%).
IR (neat): 2976 (s), 2938 (s), 2876 (s), 1730 (w), 1682 (s), 1568 (s),
1449 (m), 1377 (m), 1354 (m), 1269 (s), 1139 (s), 1056 (s), 992 (m),
792 cm–1 (m).
MS (EI, 70 eV): m/z (%) = 371 (M+, 1), 326 (8), 281 (29), 268 (7),
199 (6), 186 (6), 167 (3), 154 (6), 125 (5), 116 (4), 103 (100), 75
(39).
1H NMR (CDCl3, 300 MHz): d = 1.21 (t, J = 7.2 Hz, 6 H, 2 × CH3),
1.24 (t, J = 7.2 Hz, 3 H, CH3), 1.63 (quint, J = 6.6 Hz, 2 H, CH2),
1.75 (quint, J = 6.6 Hz, 2 H, CH2), 3.12 (t, J = 6.6 Hz, 2 H, CH2),
3.30 (d, J = 5.4 Hz, 2 H, NCH2), 3.36 (t, J = 6.6 Hz, 2 H, CH2Cl),
3.50–3.60 (m, 2 H, OCH2), 3.68–3.78 (m, 2 H, OCH2), 4.07 (q,
J = 7.2 Hz, 2 H, OCH2), 4.61 (s, 1 H, CH), 4.77 (t, J = 5.4 Hz, 1 H,
OCH), 8.62 (br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 14.6, 15.3 (2 C, CH3), 19.1, 23.1,
26.2 (CH2), 51.2 (NCH2), 55.2 (CH2Cl), 57.9, 63.3 (2 C, OCH2),
81.3 (CH=C), 99.2 (OCH), 162.3 (N–C=CH), 168.8 (O=C–O).
HRMS (ESI): m/z calcd for C21H41NO4 [M+]: 371.3030; found:
371.3021.
Ethyl 3-[(2,2-Dimethoxyethyl)amino]tetradec-2-enoate (3q)
Starting with ethyl 3-oxotetradecanoate (1o) (0.135 g, 0.5 mmol), 2-
azido-1,1-dimethoxyethane (2b) (0.079 g, 0.6 mmol) and Ph3P
(0.197 g, 0.8 mmol) in THF (5 mL), 3q was isolated after chroma-
tography (silica gel, n-hexane–EtOAc, 100:1 → 3:1) as a light yel-
low oil (0.160 g, 90%).
IR (neat): 3282 (w), 2926 (s), 2856 (s), 1743 (w), 1718 (w), 1654
(s), 1604 (s), 1501 (s), 1459 (s), 1371 (s), 1288 (s), 1240 (s), 1178
(s), 1134 (s), 1083 (s), 1055 (s), 982 (m), 831 (w), 789 (m), 714 (m),
664 cm–1 (w).
MS (EI, 70 eV): m/z (%) = 285 ([M – Cl]+, 8), 256 (19), 240 (60),
212 (7), 194 (11), 182 (51), 166 (16), 154 (29), 138 (12), 124 (8),
122 (29), 116 (82), 103 (100), 89 (31), 75 (92).
1H NMR (CDCl3, 300 MHz): d = 0.88 (t, J = 6.9 Hz, 3 H, CH3),
1.25 (t, J = 7.2 Hz, 3 H, CH3), 1.26–1.34 (m, 16 H, 8 × CH2), 1.51
(quint, J = 7.5 Hz, 2 H, CH2), 2.17 (t, J = 7.8 Hz, 2 H, CH2), 3.32
(dd, J = 6.0, 5.7 Hz, 2 H, NCH2), 3.42 (s, 6 H, 2 × OCH3), 4.09 (q,
J = 7.2 Hz, 2 H, OCH2), 4.41 (t, J = 5.7 Hz, 1 H, OCH), 4.48 (s, 1
H, CH), 8.60 (br s, 1 H, NH).
HRMS (ESI): m/z calcd for C15H28ClNO4 [M+]: 321.1701; found:
321.1702.
Ethyl 9-Chloro-3-[(2,2-diethoxyethyl)amino]non-2-enoate (3t)
Starting with ethyl 9-chloro-3-oxononanoate (1q) (0.470 g, 2.0
mmol), 2-azido-1,1-diethoxyethane (2a) (0.382 g, 2.4 mmol) and
Ph3P (0.787 g, 3.0 mmol) in THF (10 mL), 3t was isolated after
Synthesis 2009, No. 2, 227–242 © Thieme Stuttgart · New York

234
E. Bellur et al.
PAPER
chromatography (silica gel, n-hexane–EtOAc, 100:1 → 5:1) as a
13C NMR (CDCl3, 75 MHz): d = 14.5 (2 C), 18.3, 28.0 (CH3), 45.3
(NCH2), 62.4 (2 × OCH2), 95.0 (CH=C), 101.0 (OCH), 162.0 (N–
C=CH), 193.9 (C=O).
MS (EI, 70 eV): m/z (%) = 215 (M+, 10), 170 (17), 140 (4), 126 (6),
111 (44), 103 (100), 96 (23), 82 (44), 75 (93).
slightly light yellow oil (0.569 g, 81%).
IR (neat): 2977 (s), 2935 (s), 2869 (s), 1741 (m), 1721 (m), 1652 (s),
1605 (s), 1501 (m), 1453 (m), 1347 (m), 1285 (s), 1235 (s), 1173 (s),
1132 (s), 1058 (s), 789 (m), 731 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 1.22 (t, J = 7.2 Hz, 6 H, 2 × CH3),
1.24 (t, J = 7.2 Hz, 3 H, CH3), 1.29–1.59 (m, 6 H, 3 × CH2), 1.77
(quint, J = 7.2 Hz, 2 H, CH2), 2.20 (t, J = 7.5 Hz, 2 H, CH2), 3.32
(dd, J = 6.3, 5.7 Hz, 2 H, NCH2), 3.53 (t, J = 6.6 Hz, 2 H, CHCl),
3.51–3.61 (m, 2 H, OCH2), 3.68–3.78 (m, 2 H, OCH2), 4.09 (q,
J = 7.2 Hz, 2 H, OCH2), 4.47 (s, 1 H, CH), 4.51 (t, J = 5.7 Hz, 1 H,
OCH), 8.61 (br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 14.1, 14.8 (2 C, CH3), 26.1, 27.3,
28.1, 31.9, 32.0 (CH2), 44.4 (CH2Cl), 45.1 (NCH2), 57.6 (OCH2),
62.5 (2 C, OCH2), 81.8 (CH=C), 101.4 (OCH), 164.4 (N–C=CH),
169.9 (O=C–O).
MS (EI, 70 eV): m/z (%) = 349 (M+, 2), 314 (1), 306 (2), 304 (7),
246 (1), 202 (1), 200 (3), 148 (1), 146 (4), 130 (13), 114 (2), 103
(100), 96 (2), 85 (3), 83 (6), 75 (40).
HRMS (ESI): m/z calcd for C17H32ClNO4 [M+]: 349.2014; found:
349.2007.
HRMS (ESI): m/z calcd for C11H21NO3 [M+]: 215.1516; found:
215.1511.
5-[(2,2-Diethoxyethyl)amino]hept-4-en-3-one (3w)
Starting with 3,5-heptanedione (1t) (0.41 mL, 3.0 mmol), 2-azido-
1,1-diethoxyethane (2a) (0.573 g, 3.6 mmol) and Ph3P (1.180 g, 4.5
mmol) in THF (15 mL), 3w was isolated after chromatography (sil-
ica gel, n-hexane–EtOAc, 100:1 → 3:1) as a slightly light yellow oil
(0.713 g, 98%).
IR (neat): 3409 (br, w), 3183 (br, w), 2976 (m), 2933 (m), 2883 (w),
1613 (s), 1577 (s), 1516 (w), 1455 (w), 1376 (w), 1349 (w), 1280
(w), 1237 (w), 1128 (m), 1067 (s), 810 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 1.10 (t, J = 7.6 Hz, 3 H, CH3),
1.14 (t, J = 7.6 Hz, 3 H, CH3), 1.23 (t, J = 7.2 Hz, 6 H, 2 × CH3),
2.22–2.31 (m, 4 H, 2 × CH2), 3.36 (dd, J = 6.0, 6.0 Hz, 2 H, NCH2),
3.52–3.61 (m, 2 H, OCH2), 3.69–3.78 (m, 2 H, OCH2), 4.54 (t,
J = 5.4 Hz, 1 H OCH), 5.00 (s, 1 H, CH=C), 10.84 (br s, 1 H, NH).
Ethyl 10-Chloro-3-[(2,2-diethoxyethyl)amino]dec-2-enoate (3u)
Starting with ethyl 10-chloro-3-oxodecanoate (1r) (0.600 g, 2.4
mmol), 2-azido-1,1-diethoxyethane (2a) (0.462 g, 2.9 mmol) and
Ph3P (0.949 g, 3.6 mmol) in THF (12 mL), 3u was isolated after
chromatography (silica gel, n-hexane–EtOAc, 100:1 → 3:1) as a
slightly light yellow oil (0.727 g, 83%).
13C NMR (CDCl3, 75 MHz): d = 10.3, 12.2, 15.4 (2C, CH3), 25.2,
35.1 (CH2), 45.7 (NCH2), 63.3 (2 × OCH2), 92.6 (CH=C), 101.9
(OCH), 168.1 (N–C=CH), 198.7 (C=O).
MS (EI, 70 eV): m/z (%) = 243 (M+, 7), 214 (2), 198 (7), 168 (3),
140 (15), 124 (7), 112 (9), 103 (100).
HRMS (ESI): m/z calcd for C13H25NO3 [M+]: 243.1829; found:
243.1833.
IR (neat): 3282 (w), 2978 (s), 2933 (s), 2864 (s), 1653 (s), 1603 (s),
1501 (s), 1452 (s), 1375 (s), 1282 (s), 1233 (s), 1174 (s), 1126 (s),
1059 (s), 939 (w), 850 (w),790 (s), 718 (m), 854 cm–1 (m).
1H NMR (CDCl3, 300 MHz): d = 1.24 (t, J = 7.2 Hz, 6 H, 2 × CH3),
1.26 (t, J = 7.2 Hz, 3 H, CH3), 1.31–1.52 (m, 8 H, 4 × CH2), 1.77
(quint, J = 7.5 Hz, 2 H, CH2), 2.19 (t, J = 7.5 Hz, 2H, CH2), 3.32
(dd, J = 6.0, 5.7 Hz, 2 H, NCH2), 3.53 (t, J = 6.9 Hz, 2 H, CH2Cl),
3.53–3.63 (m, 2 H, OCH2), 3.69–3.79 (m, 2 H, OCH2), 4.09 (q,
J = 7.2 Hz, 2 H, OCH2), 4.47 (s, 1 H, CH), 4.51 (t, J = 5.7 Hz, 1 H,
OCH), 8.63 (br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 14.3, 15.0 (2 C, CH3), 26.4, 27.5,
28.3, 28.9, 32.2, 32.3 (CH2), 44.7 (CH2Cl), 45.4 (NCH2), 58.0, 62.8
(2 C, OCH2), 82.0 (CH=C), 101.7 (OCH), 164.9 (N–C=CH), 170.2
(O=C–O).
MS (EI, 70 eV): m/z (%) = 363 (M+, 1), 320 (1), 318 (4), 260 (1),
214 (2), 200 (2), 161 (2), 143 (2), 130 (10), 115 (2), 103 (100), 75
(45).
Anal. Calcd for C13H25NO3 (243.342): C, 64.16; H, 10.36. Found:
C, 64.16; H, 10.42.
3-[(2,2-Diethoxyethyl)amino]-1-phenylbut-2-en-1-one (3x)
Starting with benzoylacetone 1u (0.200 g, 1.2 mmol), 2-azido-1,1-
diethoxyethane (2a) (0.236 g, 1.5 mmol) and Ph3P (0.656 g, 2.5
mmol) in THF (10 mL), 3x was isolated after chromatography (sil-
ica gel, n-hexane–EtOAc, 100:1 → 1:1) as a light yellow oil (0.322
g, 97%).
IR (neat): 3060 (w), 2977 (m), 2930 (w), 2830 (w), 2883 (w), 1606
(s), 1550 (s), 1525 (m), 1483 (w), 1444 (m), 1378 (m), 1327 (s),
1294 (s), 1245 (m), 1172 (w), 1127 (s), 1065 (s), 1031 (m), 818 (w),
793 (w), 740 (m), 714 (w), 684 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 1.25 (t, J = 7.1 Hz, 6 H, 2 × CH3),
2.10 (s, 3 H, CH3), 3.46 (dd, J = 6.4, 5.6 Hz, 2 H, NCH2), 3.59 (dq,
J = 9.3, 7.1 Hz, 2 H, OCH2), 3.76 (dq, J = 9.3, 7.1 Hz, 2 H, OCH2),
4.59 (t, J = 5.6 Hz, 1 H, OCH), 5.68 (s, 1 H, CH=C), 7.40 (m, 3 H,
3 × CH of Ph), 7.86 (m, 2 H, 2 × CH of Ph), 11.42 (br s, 1 H, NH).
Anal. Calcd for C18H34ClNO4 (363.920): C, 59.41; H, 9.42. Found:
C, 59.06; H, 9.44.
13C NMR (CDCl3, 75 MHz): d = 15.2 (2C), 19.5 (CH3), 46.3
(NCH2), 63.3 (2 C, OCH2), 92.5 (CH=C), 101.1 (OCH), 126.7 (2
C), 127.9 (2 C), 130.2 (CH of Ph), 140.3 (C of Ph), 164.7 (N–
C=CH), 187.8 (C=O).
MS (EI, 70 eV): m/z (%) = 277 (M+, 7), 232 (6), 199 (7), 174 (7),
160 (2), 158 (6), 144 (1), 117 (1), 103 (100), 91 (14), 77 (17).
4-[(2,2-Diethoxyethyl)amino]pent-3-en-2-one (3v)
Starting with acetyl acetone (1s) (0.300 g, 3.0 mmol), 2-azido-1,1-
diethoxyethane (2a) (0.573 g, 3.6 mmol) and Ph3P (1.180 g, 4.5
mmol) in THF (15 mL), 3v was isolated after chromatography (sil-
ica gel, n-hexane–EtOAc, 100:1 → 1:1) as a slightly light yellow oil
(0.635 g, 98%).
HRMS (ESI): m/z calcd for C16H23NO3 [M+]: 277.16779; found:
277.16803.
IR (neat): 2977 (s), 2928 (m), 2883 (m), 1616 (s), 1576 (s), 1514 (s),
1444 (s), 1375 (m), 1355 (s), 1293 (s), 1242 (m), 1127 (s), 1065 (s),
1024 (m), 979 (w), 797 (w), 741 cm–1 (m).
1H NMR (CDCl3, 300 MHz): d = 1.24 (t, J = 7.2 Hz, 6 H, 2 × CH3),
1.94 (s, 3 H, CH3), 2.01 (s, 3 H, CH3), 3.36 (dd, J = 6.3, 5.7 Hz, 2
H, NCH2), 3.52–3.62 (m, 2 H, OCH2), 3.69–3.79 (m, 2 H, OCH2),
4.53 (t, J = 5.7 Hz, 1 H OCH), 4.99 (s, 1 H, CH=C), 10.80 (br s, 1
H, NH).
Anal. Calcd for C16H23NO3 (277.363): C, 69.29; H, 8.36. Found: C,
69.61; H, 8.37.
3-[(2,2-Dimethoxyethyl)amino]-1-(2-methoxyphenyl)but-2-en-
1-one (3y)
Starting with benzoylacetone 1v (1.153 g, 6.0 mmol), 2-azido-1,1-
dimethoxyethane (2b) (0.983 g, 7.5 mmol) and Ph3P (3.934 g, 15.0
Synthesis 2009, No. 2, 227–242 © Thieme Stuttgart · New York

PAPER
Staudinger–Aza-Wittig Reactions of 1,3-Dicarbonyl Compounds
235
mmol) in THF (10 mL), 3y was isolated after chromatography (sil-
ica gel, n-hexane–EtOAc, 100:1 → 1:1) as a light yellow oil (0.800
g, 50%).
3-[(2,2-Diethoxyethyl)amino]-5,5-dimethylcyclohex-2-en-1-one
(6b)
Starting with dimedone (5b) (0.421 g, 3.0 mmol), 2-azido-1,1-di-
ethoxyethane (2a) (0.573 g, 3.6 mmol), and Ph3P (1.180 g, 4.5
mmol) in THF (15 mL), 6b was isolated after chromatography (sil-
ica gel, n-hexane–EtOAc, 50:1 → EtOAc → acetone) as a light yel-
low oil (0.703 g, 92%).
IR (neat): 3067 (w), 2991 (m), 2936 (w), 2833 (w), 1593 (s), 1580
(s), 1538 (m), 1434 (m), 1310 (m), 1070 (s), 1020 (m), 752 cm–1 (s).
1H NMR (CDCl3, 250 MHz): d = 1.96 (s, 3 H, CH3), 3.35 (m, 2 H,
CH2), 3.37 (s, 6 H, OCH3), 3.78 (s, 3 H, OCH3), 4.41 (t, 3J = 6.0 Hz,
1 H, CH), 5.53 (s, 1 H, CH), 6.83 (d, 3J = 8.2 Hz, 1 H, CHAr), 6.89
(d, 3J = 7.5 Hz, 1 H, CHAr), 7.25 (dd, 3J = 7.6 Hz, 4J = 2.0 Hz, 1 H,
CHAr), 7.51 (dd, 3J = 7.8 Hz, 4J = 2.0 Hz, 1 H, CHAr), 11.24 (br s, 1
H, NH).
13C NMR (CDCl3, 62 MHz): d = 15.5 (CH3), 45.4 (NCH2), 54.2
(2 OCH3), 55.6 (OCH3), 97.5 (CH=C), 103.4 (CH), 111.3, 120.4,
129.6. 130.6 (CHAr), 131.3, 156.8 (CAr), 163.9 (N–C=CH), 188.9
(C=O).
MS (EI, 70 eV): m/z (%) = 279 (M+, 17), 248 (9), 188 (15), 135 (27),
121 (38), 75 (100), 47 (7).
HRMS (ESI): m/z calcd for C15H21NO4 [M+]: 279.14651; found;
279.14672.
IR (neat): 3259 (m), 3069 (m), 2967 (s), 2935 (s), 2878 (s), 1738
(m), 1540 (s), 1452 (s), 1425 (m), 1410 (m), 1376 (s), 1271 (s), 1242
(s), 1131 (s), 1065 (s), 960 (w), 932 (w), 891 (w), 809 (m), 732 (m),
703 (w), 660 (w), 607 (m), 560 (m), 482 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 1.07 (s, 6 H, 2 × CH3), 1.22 (t,
J = 7.2 Hz, 6 H, 2 × CH3), 2.17 (s, 2 H, CH2), 2.27 (s, 2 H, CH2),
3.23 (dd, J = 5.4, 5.4 Hz, 2 H, NCH2), 3.50–3.60 (m, 2 H, OCH2),
3.65–3.75 (m, 2 H, OCH2), 4.67 (t, J = 5.4 Hz, 1 H, OCH), 5.12 (s,
1 H, CH=C), 5.89 (br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 14.9 (2 × CH3), 27.8 (2 × CH3),
32.3 (C), 42.8 (CH2), 44.9 (NCH2), 49.9 (CH2), 62.2 (2 × OCH2),
94.6 (CH=C), 99.1 (OCH), 163.2 (N–C=CH), 196.2 (C=O).
MS (EI, 70 eV): m/z (%) = 255 (M+, 8), 210 (2), 181 (2), 164 (6),
151 (2), 138 (2), 122 (1), 103 (77), 84 (100), 75 (47).
HRMS (ESI): m/z calcd for C14H25NO3 [M+]: 255.1829; found:
1-(2-Chlorophenyl)-3-[(2,2-dimethoxyethyl)amino]but-2-en-1-
one (3z)
Starting with benzoylacetone 1w (1.476 g, 7.5 mmol), 2-azido-1,1-
dimethoxyethane (2b) (1.493 g, 9.3 mmol) and Ph3P (4.921 g, 18.7
mmol) in THF (10 mL), 3z was isolated after chromatography (sil-
ica gel, n-hexane–EtOAc, 100:1 → 1:1) as a light yellow oil (1.000
g, 52%).
255.1824.
3-[(2,2-Diethoxyethyl)amino]-5-methylcyclohex-2-en-1-one (6c)
Starting with 5-methyl-1,3-cyclohexanedione (5c) (0.386 g, 3.0
mmol), 2-azido-1,1-diethoxyethane (2a) (0.573 g, 3.6 mmol) and
Ph3P (1.180, 4.5 mmol) in THF (15 mL), 6c was isolated after chro-
matography (silica gel, n-hexane–EtOAc, 50:1 → EtOAc → ace-
tone) as a light brown oil (0.724 g, 94%).
IR (neat): 3067 (w), 2991 (m), 2936 (w), 2833 (w), 1593 (s), 1580
(s), 1538 (m), 1434 (m), 1310 (m), 1070 (s), 1020 (m), 752 cm–1 (s).
1H NMR (CDCl3, 250 MHz): d = 1.97 (s, 3 H, CH3), 3.36 (m, 2 H,
CH2), 3.37 (s, 6 H, OCH3), 4.42 (t, 3J = 6.0 Hz, 1 H, CH), 5.25 (s, 1
H, CH), 7.14–7.17 (m, 1 H, CHAr), 7.25–7.29 (m, 1 H, CHAr), 7.34–
7.38 (m, 1 H, CHAr), 11.12 (br s, 1 H, NH).
13C NMR (CDCl3, 62 MHz): d = 19.4 (CH3), 45.5 (NCH2), 54.8
(2 OCH3), 96.8 (CH=C), 103.4 (CH), 112.4, 129.1, 129.7, 130.0
(CHAr), 130.8, 141.4 (CAr), 165.0 (N–C=CH), 188.9 (C=O).
MS (EI, 70 eV): m/z (%) = 285 (M+, 37Cl, 3), 283 (M+, 35Cl, 9), 252
(5), 208 (6), 188 (5), 125 (10), 111 (7), 75 (100), 47 (6).
HRMS (ESI): m/z calcd for C14H18ClNO3 [M+, 35Cl]: 283.09752;
found; 283.09752.
IR (neat): 3260 (m), 3070 (m), 2968 (s), 2933 (s), 2882 (m), 1547
(s), 1451 (s), 1427 (m), 1412 (m), 1373 (m), 1272 (s), 1245 (m),
1134 (m), 1067 (s), 808 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 1.03–1.13 (m, 3 H, CH3), 1.23 (dt,
J = 7.2, 1.2 Hz, 6 H, 2 × CH3), 2.00–2.34 (m, 5 H, 2 × CH2, CH),
3.22 (dd, J = 5.4, 5.4 Hz, 2 H, NCH2), 3.50–3.60 (m, 2 H, OCH2),
3.65–3.75 (m, 2 H, OCH2), 4.66 (t, J = 5.4 Hz, 1 H, OCH), 4.80 (br
s, 1 H, NH), 5.13 (s, 1 H, CH=C).
13C NMR (CDCl3, 75 MHz): d = 15.1 (2 × CH3), 20.3 (CH3), 27.5
(CH), 35.4, 42.1 (CH2), 44.8 (NCH2), 62.2 (2 × OCH2), 95.8
(CH=C), 99.8 (OCH), 163.4 (N–C=CH), 196.0 (C=O).
MS (EI, 70 eV): m/z (%) = 241 (M+, 5), 196 (1), 151 (5), 138 (3),
124 (2), 103 (100), 74 (38).
HRMS (ESI): m/z calcd for C13H23NO3 [M+]: 241.16779;
241.16770.
3-[(2,2-Diethoxyethyl)amino]cyclohex-2-en-1-one (6a)
Starting with 1,3-cyclohexanedione (5a) (0.336 g, 3.0 mmol), 2-azi-
do-1,1-diethoxyethane (2a) (0.573 g, 3.6 mmol) and Ph3P (1.180,
4.5 mmol) in THF (15 mL), 6a was isolated after chromatography
(silica gel, n-hexane–EtOAc, 50:1 → EtOAc → acetone) as a light
brown oil (0.664 g, 97%).
3-[(2,2-Diethoxyethyl)amino]-5-phenylcyclohex-2-en-1-one
(6d)
Starting with 5-phenyl-1,3-cyclohexanedione (5d) (0.588 g, 3.0
mmol), 2-azido-1,1-diethoxyethane (2a) (0.573 g, 3.6 mmol) and
Ph3P (1.180, 4.5 mmol) in THF (15 mL), 6d was isolated after chro-
matography (silica gel, n-hexane–EtOAc, 50:1 → EtOAc) as a light
brown solid (0.838 g, 92%).
IR (neat): 3260 (w), 3071 (w), 2976 (m), 2935 (m), 2880 (m), 1663
(w), 1551 (s), 1451 (m), 1372 (m), 1319 (w), 1290 (w), 1246 (m),
1190 (m), 1133 (s), 1065 cm–1 (s).
1H NMR (CDCl3, 300 MHz): d = 1.23 (t, J = 7.2 Hz, 6 H, 2 × CH3),
1.97 (t, J = 6.6 Hz, 2 H, CH2), 2.32 (t, J = 6.6 Hz, 2 H, CH2), 2.36
(t, J = 6.6 Hz, 2 H, CH2), 3.21 (dd, J = 5.2, 5.2 Hz, 2 H, NCH2),
3.50–3.60 (m, 2 H, OCH2), 3.66–3.76 (m, 2 H, OCH2), 4.64 (t,
J = 5.2 Hz, 1 H, OCH), 4.75 (br s, 1 H, NH), 5.13 (s, 1 H, CH=C).
13C NMR (CDCl3, 75 MHz): d = 14.2 (2 × CH3), 21.0, 28.2, 35.5
(CH2), 44.4 (NCH2), 61.3 (OCH2), 98.5 (CH=C), 101.9 (OCH),
164.8 (N–C=CH), 195.7 (C=O).
MS (EI, 70 eV): m/z (%) = 227 (M+, 4), 186 (1), 136 (6), 124 (4),
103 (100), 75 (67).
IR (KBr): 3243 (s), 3065 (s), 2975 (m), 2934 (m), 2888 (m), 1545
(s), 1441 (s), 1374 (m), 1274 (s), 1239 (s), 1133 (s), 1069 (s), 757
(w), 701 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 1.23 (dt, J = 7.2, 1.4 Hz, 6 H,
2 × CH3), 2.44–2.75 (m, 4 H, 2 × CH2), 3.24 (dd, J = 5.1, 5.1 Hz, 2
H, NCH2), 3.29–3.41 (m, 1 H, CHPh), 3.50–3.61 (m, 2 H, OCH2),
3.66–3.76 (m, 2 H, OCH2), 4.65 (t, J = 5.1 Hz, 1 H, OCH), 4.81 (br
s, 1 H, NH), 5.22 (s, 1 H, CH = C), 7.23–7.27 (m, 3 H, 3 × CH of
Ph), 7.31–7.34 (m, 2 H, 2 × CH of Ph).
Anal. Calcd for C12H21NO3 (227.303): C, 63.41; H, 9.31: Found: C,
63.09; H, 9.12.
Synthesis 2009, No. 2, 227–242 © Thieme Stuttgart · New York

236
E. Bellur et al.
PAPER
13C NMR (CDCl3, 75 MHz): d = 15.0 (2 × CH3), 36.8 (CH2), 39.6
(CHPh), 43.3 (NCH2), 45.1 (CH2), 62.4 (2 × OCH2), 96.1 (CH=C),
99.2 (OCH), 126.4 (2 C), 126.6, 128.4 (2 C, CH of Ph), 142.9 (C of
Ph), 163.6 (N–C=CH), 196.1 (C=O).
HRMS (ESI): m/z calcd for C13H21NO4 [M+]: 255.14706; found:
255.14772.
Methyl 2-Methyl-1H-pyrrole-3-carboxylate (4a)
IR (neat): 3312 (m), 2978 (s), 2952 (w), 2933 (w), 2867 (m), 1707
(s), 1680 (s), 1607 (w), 1580 (m), 1493 (w), 1452 (s), 1408 (w),
1381 (m), 1348 (w), 1329 (m), 1268 (m), 1226 (w), 1202 (m), 1177
(w), 1125 (s), 1076 (w), 1053 (w), 1026 (w), 900 (w), 844 (w), 790
(w), 726 cm–1 (w).
MS (EI, 70 eV): m/z (%) = 303 (M+, 8), 258 (3), 213 (7), 200 (4),
170 (5), 103 (100), 91 (46), 77 (32).
HRMS (ESI): m/z calcd for C18H25NO3 [M+]: 303.18344; found:
303.18338.
1H NMR (CDCl3, 300 MHz): d = 2.53 (s, 3 H, CH3), 3.80 (s, 3 H,
OCH3), 6.55 (d, J = 2.7 Hz, 1 H, CH), 6.56 (d, J = 2.7 Hz, 1 H, CH),
8.23 (br s, 1 H, NH).
UV/Vis (MeCN,): λmax (log ε) = 280 nm (4.29).
Synthesis of Pyrroles (4); Representative Procedures
Method A: To 3x (0.050 g, 0.18 mmol) in CH2Cl2 (3 mL) was add-
ed TFA (0.14 mL, 1.8 mmol) at 0 °C. The reaction mixture was al-
lowed to warm to 20 °C during 12 h and was stirred for 4 h at 20 °C.
The solvent was removed in vacuo and the residue was purified by
column chromatography (silica gel, n-hexane–EtOAc, 50:1 → 3:1)
to give 4r as a light yellow solid (0.027 g, 82%).
13C NMR (CDCl3, 75 MHz): d = 13.2 (CH3), 50.8 (OCH3), 110.4
(CH), 110.5 (C), 115.8 (CH), 135.3 (C), 166.1 (O=C–O).
MS (EI, 70 eV): m/z (%) = 139 (M+, 46), 124 (19), 107 (100), 80
(33).
HRMS (EI, 70 eV): m/z calcd for C7H9NO2: 139.0633 [M+]; found:
Method B: To 3x (0.050 g, 0.18 mmol) in CH2Cl2 (3 mL) was add-
ed Me3SiOTf (0.050 g, 0.18 mmol) at 0 °C. The reaction mixture
was allowed to warm to 20 °C during 12 h and was stirred for 4 h at
20 °C. The solvent was removed in vacuo and the residue was puri-
fied by column chromatography (silica gel, n-hexane–EtOAc, 50:1
→ 1:1) to give 4r as a light yellow solid (0.026 g, 79%).
139.0633 2 ppm.
Ethyl 2-Methyl-1H-pyrrole-3-carboxylate (4b)
Starting with 3b (0.100 g, 0.4 mmol) in DMSO (5 mL), 4b was iso-
lated after chromatography (silica gel, n-hexane–EtOAc, 100:1 →
1:1) as a light brown solid (0.036 g, 58%); mp 64 °C.
Method C: A DMSO solution (5 mL) of 3x (0.100 g, 0.36 mmol)
was stirred at 150 °C for 24 h. After cooling to 20 °C, H2O (10 mL)
was added and the mixture was extracted with Et2O (4 × 15 mL).
The combined organic extracts were dried (Na2SO4), filtered and
the filtrate was concentrated in vacuo. The residue was purified by
column chromatography (silica gel, n-hexane–EtOAc, 50:1 → 1:1)
to give 4r as a light yellow solid (0.048 g, 72%).
IR (KBr): 3294 (s), 2985 (m), 2938 (w), 2906 (w), 1697 (s), 1675
(s), 1578 (m), 1499 (m), 1447 (m), 1411 (m), 1369 (m), 1325 (s),
1267 (s), 1227 (w), 1201 (s), 1127 (s), 1095 (s), 1053 (s), 901 (m),
781 (m), 754 (m), 722 cm–1 (m).
1H NMR (CDCl3, 300 MHz): d = 1.34 (t, J = 7.2 Hz, 3 H,
OCH2CH3), 2.52 (s, 3 H, CH3), 4.27 (q, J = 7.2 Hz, 2 H, OCH2),
6.56 (d, J = 2.4 Hz, 2 H, 2 × CH), 8.51 (br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 13.2, 14.5 (CH3), 59.4 (OCH2),
Methyl 2-Methyl-1H-pyrrole-3-carboxylate (4a)
Method A: Starting with 3a (0.100 g, 0.4 mmol) and TFA (0.33
mL, 4.3 mmol) in CH2Cl2 (5 mL), 4a was isolated after chromatog-
raphy (silica gel, n-hexane–EtOAc, 50:1 → 3:1) as a light brown
solid (0.013 g, 22%).
110.4 (CH), 111.7 (C), 115.7 (CH), 135.2 (C), 165.8 (O=C–O).
MS (EI, 70 eV): m/z (%) = 153 (M+, 95), 124 (61), 108 (100).
HRMS (EI, 70 eV): m/z calcd for C8H11NO2: 153.0790 [M+]; found:
153.0790 2 ppm.
Method B: Starting with 3a (0.100 g, 0.43 mmol) and Me3SiOTf
(0.096 g, 0.43 mmol) in CH2Cl2 (5 mL) at 0 °C, 4a was isolated after
chromatography (silica gel, n-hexane–EtOAc, 50:1 → 1:1) as a
light brown solid (0.021 g, 35%).
Isopropyl 2-Methyl-1H-pyrrole-3-carboxylate (4c)
Starting with 3c (0.200 g, 0.8 mmol) and Me3SiOTf (0.172 g, 0.8
mmol) in CH2Cl2 (10 mL), 4c was isolated after chromatography
(silica gel, n-hexane–EtOAc, 50:1 → 3:1) as a light brown oil
(0.064 g, 50%).
Method C: Starting with 3a (0.100 g, 0.43 mmol) in DMSO (5 mL),
4a¢ (0.021 g, 19%) and 4a (0.024 g, 40%) were isolated after chro-
matography (silica gel, n-hexane–EtOAc, 100:1 → 1:1) as light
brown oil and solid, respectively.
IR (neat): 3318 (m), 2987 (s), 2936 (w), 2895 (w), 1707 (s), 1689
(s), 1672 (s), 1576 (m), 1495 (w), 1412 (w), 1373 (m), 1327 (m),
1268 (m), 1225 (w), 1202 (m), 1125 (s), 1086 (m), 1053 (m), 902
(w), 788 (w), 724 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 1.26 (d, J = 6.3 Hz, 6 H, 2 × CH3),
2.53 (s, 3 H, CH3), 5.04 (sept, J = 6.3 Hz, 1 H, OCH), 6.55 (d,
J = 2.7 Hz, 1 H, CH), 6.58 (d, J = 2.7 Hz, 1 H, CH), 8.55 (br s, 1 H,
NH).
13C NMR (CDCl3, 75 MHz): d = 13.2, 21.8 (2 C, CH3), 68.6 (OCH),
110.3 (CH), 111.9 (C), 115.8 (CH), 135.2 (C), 165.6 (O=C–O).
MS (EI, 70 eV): m/z (%) = 167 (M+, 67), 124 (42), 108 (100), 80
(37).
Methyl 1-(2,2-Diethoxyethyl)-2-methyl-1H-pyrrole-3-carboxy-
late (4a¢)
IR (neat): 3410 (br), 3367 (br), 2977 (w), 2953 (w), 2929 (w), 2857
(w), 1725 (s), 1704 (s), 1630 (w), 1601 (w), 1556 (w), 1525 (w),
1508 (w), 1439 (m), 1401 (w), 1376 (w), 1293 (m), 1257 (s), 1227
(s), 1195 (m), 1114 (s), 1063 (s), 776 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 1.16 (t, J = 7.2 Hz, 6 H, 2 × CH3),
2.55 (s, 3 H, CH3), 3.32–3.42 (m, 2 H, OCH2), 3.62–3.72 (m, 2 H,
OCH2), 3.79 (s, 3 H, OCH3), 3.93 (d, J = 5.4 Hz, 2 H, NCH2),
4.53,(t, J = 5.4 Hz, 1 H, OCH), 6.51 (d, J = 3.0 Hz, 1 H, CH), 6.55
(d, J = 3.0 Hz, 1 H, CH).
13C NMR (CDCl3, 75 MHz): d = 11.1, 15.2 (2 C, CH3), 50.0
(NCH2), 50.7 (OCH3), 63.9 (2 C, OCH2), 102.2 (OCH), 109.5 (CH),
111.9 (C), 120.9 (CH), 136.3 (C), 166.0 (O=C–O).
HRMS (EI, 70 eV): m/z calcd for C9H13NO2: 167.0946 [M+]; found:
167.0946 2 ppm.
Isobutyl 2-Methyl-1H-pyrrole-3-carboxylate (4d)
Starting with 3d (0.200 g, 0.7 mmol) and Me3SiOTf (0.163 g, 0.7
mmol) in CH2Cl2 (10 mL), 4d was isolated after chromatography
(silica gel, n-hexane–EtOAc, 50:1 → 3:1) as a light brown oil
(0.059 g, 42%).
MS (EI, 70 eV): m/z (%) = 255 (M+, 15), 223 (60), 210 (4), 192 (80),
182 (3), 178 (4), 166 (4), 164 (27), 151 (3), 132 (5), 120 (11), 103
(100), 76 (63).
Synthesis 2009, No. 2, 227–242 © Thieme Stuttgart · New York

PAPER
Staudinger–Aza-Wittig Reactions of 1,3-Dicarbonyl Compounds
Ethyl 2-Propyl-1H-pyrrole-3-carboxylate (4h)
237
IR (neat): 3321 (m), 2983 (s), 2941 (w), 2897 (w), 1705 (s), 1691
(s), 1673 (s), 1577 (m), 1491 (w), 1414 (w), 1371 (m), 1331 (m),
1272 (m), 1223 (w), 1200 (m), 1126 (s), 1087 (m), 1054 (m), 901
(w), 786 (w), 722 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 0.98 (d, J = 6.9 Hz, 6 H, 2 × CH3),
CH3), 1.98 (m, J = 6.9 Hz, 1 H, CH), 2.53 (s, 3 H, CH3), 3.87 (d,
J = 6.9 Hz, 2 H, OCH2), 6.54–6.58 (m, 2 H, 2 × CH), 8.53 (br s, 1
H, NH).
13C NMR (CDCl3, 75 MHz): d = 13.2, 19.1 (2 C, CH3), 27.8 (CH),
70.4 (OCH2), 110.5 (CH), 111.8 (C), 115.7 (CH), 135.2 (C), 165.4
(O=C–O).
MS (EI, 70 eV): m/z (%) = 181 (M+, 70), 124 (45), 108 (100), 80
(42).
Starting with 3i (0.200 g, 0.7 mmol) and Me3SiOTf (0.162 g, 0.7
mmol) in CH2Cl2 (10 mL) at 0 °C, 4h was isolated after chromatog-
raphy (silica gel, n-hexane–EtOAc, 50:1 → 3:1) as a light brown oil
(0.073 g, 55%).
IR (neat): 3345 (m), 2959 (m), 2873 (w), 1645 (s), 1582 (m), 1551
(m), 1491 (w), 1459 (m), 1448 (m), 1375 (m), 1305 (m), 1251 (s),
1174 (s), 1131 (s), 1103 (m), 1040 (m), 1019 (m), 843 (w), 759
cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 0.95 (t, J = 7.2 Hz, 3 H, CH3),
1.34 (t, J = 7.2 Hz, 3 H, CH3), 1.67 (sext, J = 7.5 Hz, 2 H, CH2),
2.92 (t, J = 7.5 Hz, 2 H, CH2), 4.27 (q, J = 7.2 Hz, 2 H, OCH2),
6.54–6.58 (m, J = 2.7 Hz, 2 H, 2 × CH), 8.31 (br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 13.7, 14.4 (CH3), 22.7, 29.2 (CH2),
59.3 (OCH2), 110.3 (CH), 111.1 (C), 115.8 (CH), 139.9 (C), 165.8
(O = C–O).
HRMS (ESI): m/z calcd for C10H15NO2 [M+]: 181.11028; found:
181.11042.
2-Methoxyethyl 2-Methyl-1H-pyrrole-3-carboxylate (4e)
Starting with 3f (0.100 g, 0.4 mmol) in DMSO (2 mL), 4e was iso-
lated after chromatography (silica gel, n-hexane–EtOAc, 100:1 →
1:1) as a light brown solid (0.034 g, 51%).
MS (EI, 70 eV): m/z (%) = 181 (M+, 62), 166 (2), 152 (100), 136
(45), 124 (87), 120 (11), 108 (49).
HRMS (EI, 70 eV): m/z calcd for C10H15NO2: 181.1103 [M+];
found: 181.1103 2 ppm.
IR (neat): 3319 (br), 2930 (w), 1684 (s), 1455 (m), 1322 (w), 1269
(m), 1231 (w), 1196 (w), 1126 (s), 1099 (m), 1060 cm–1 (w).
Ethyl 2-Heptyl-1H-pyrrole-3-carboxylate (4i)
Route 1: Starting with 3k (0.250 g, 0.8 mmol) and Me3SiOTf
(0.185 g, 0.8 mmol) in CH2Cl2 (10 mL), 4i was isolated after chro-
matography (silica gel, n-hexane–EtOAc, 50:1 → 3:1) as a light
brown oil (0.118 g, 60%).
1H NMR (CDCl3, 300 MHz): d = 2.52 (s, 3 H, CH3), 3.42 (s, 3 H,
OCH3), 3.68–3.71 (m, 2 H, OCH2), 4.36–4.39 (m, 2 H, OCH2),
6.54–6.58 (m, 2 H, 2 × CH), 8.53 (br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 13.2 (CH3), 58.9 (OCH3), 62.4,
70.8 (OCH2), 110.5 (CH), 111.3 (C), 115.8 (CH), 135.5 (C), 165.5
(O=C–O).
MS (EI, 70 eV): m/z (%) = 183 (M+, 9), 125 (23), 108 (100), 80 (14).
HRMS (EI, 70 eV): m/z calcd for C9H13NO3: 183.0895 [M+]; found:
Route 2: Starting with 3l (0.350 g, 1.06 mmol) and Me3SiOTf
(0.236 g, 1.06 mmol) in CH2Cl2 (15 mL), 4i was isolated after chro-
matography (silica gel, n-hexane–EtOAc, 50:1 → 3:1) as a light
brown oil (0.146 g, 58%).
IR (neat): 3324 (s), 2956 (s), 2928 (s), 2871 (m), 2857 (m), 1726
(m), 1702 (s), 1673 (s), 1574 (m), 1496 (m), 1466 (s), 1394 (m),
1370 (m), 1331 (m), 1297 (m), 1264 (m), 1197 (m), 1181 (m), 1128
(s), 1096 (w), 1077 (w), 1049 (m), 1028 (w), 902 (w), 790 (w), 724
cm–1 (m).
1H NMR (CDCl3, 300 MHz): d = 0.86 (t, J = 6.9 Hz, 3 H, CH3),
1.15–1.40 (m, 11 H, CH3, 4 × CH2), 1.50–1.64 (m, 2 H, CH2), 2.92
(t, J = 7.5 Hz, 2 H, CH2), 4.27 (q, J = 7.2 Hz, 2 H, OCH2), 6.56 (d,
J = 3.0 Hz, 1 H, CH), 6.58 (d, J = 3.3 Hz, 1 H, CH), 8.21 (br s, 1 H,
NH).
13C NMR (CDCl3, 75 MHz): d = 13.9, 14.3 (CH3), 22.5, 27.3, 29.0,
29.3, 29.5, 31.7 (CH2), 59.2 (OCH2), 110.5 (CH), 110.9 (C), 115.8
(CH), 140.1 (C), 165.8 (O=C–O).
MS (EI, 70 eV): m/z (%) = 237 (M+, 40), 208 (18), 192 (12), 164
(39), 151 (38), 138 (6), 124 (100).
183.0895 2 ppm.
Allyl 2-Methyl-1H-pyrrole-3-carboxylate (4f)
Starting with 3g (0.100 g, 0.4 mmol) and Me3SiOTf (0.087 g, 0.4
mmol) in CH2Cl2 (5 mL) at 0 °C, 4f was isolated after chromatog-
raphy (silica gel, n-hexane–EtOAc, 100:1 → 3:1) as a light brown
oil (0.024 g, 37%).
IR (neat): 3337 (br, m), 2976 (w), 2928 (m), 1703 (s), 1581 (w),
1538 (w), 1447 (m), 1411 (m), 1267 (m), 1222 (s), 1175 (m), 1109
(m), 1012 (w), 994 (w), 933 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 2.53 (s, 3 H, CH3), 4.62–4.74 (m,
2 H, OCH2), 5.20–5.39 (m, 2 H, CH2=CH), 5.91–6.09 (m, 1 H,
CH=CH2), 6.55–6.58 (m, 2 H, 2 × CH), 8.35 (br s, 1 H, NH).
Anal. Calcd for C11H15NO2 (139.24): C, 68.37; H, 7.82. Found: C,
68.55; H, 7.58.
Anal. Calcd for C14H23NO2 (237.342): C, 70.85; H, 9.77. Found: C,
70.47; H, 10.10.
Methyl 2-Ethyl-1H-pyrrole-3-carboxylate (4g)
Starting with 3h (0.100 g, 0.4 mmol) and Me3SiOTf (0.091 g, 0.4
mmol) in CH2Cl2 (5 mL) at 0 °C, 4g was isolated after chromatog-
raphy (silica gel, n-hexane–EtOAc, 100:1 → 3:1) as a light brown
solid (0.024 g, 39%).
Ethyl 2-Nonyl-1H-pyrrole-3-carboxylate (4j)
Starting with 3m (0.300 g, 0.8 mmol) and Me3SiOTf (0.187 g, 0.8
mmol) in CH2Cl2 (10 mL), 4j was isolated after chromatography
(silica gel, n-hexane–EtOAc, 50:1 → 3:1) as a light brown oil
(0.127 g, 57%).
IR (KBr): 3296 (br, w), 2954 (m), 2929 (m), 1715 (s), 1445 (m),
1371 (m), 1226 (s), 1102 cm–1 (m).
1H NMR (CDCl3, 300 MHz): d = 1.25 (t, J = 7.2 Hz, 3 H, CH3),
3.00 (q, J = 7.2 Hz, 2 H, CH2), 3.79 (s, 3 H, OCH3), 6.55–6.58 (m,
2 H, 2 × CH), 8.28 (br s, 1 H, NH).
IR (neat): 3332 (m), 2957 (m), 2926 (s), 2855 (m), 1675 (s), 1464
(m), 1371 (w), 1329 (w), 1263 (w), 1196 (w), 1182 (w), 1128 (s),
1043 (w), 723 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 0.88 (t, J = 6.9 Hz, 3 H, CH3),
1.19–1.39 (m, 12 H, 6 × CH2), 1.34 (t, J = 7.2 Hz, 3 H, CH3), 1.58–
1.68 (m, 2 H, CH2), 2.94 (t, J = 7.6 Hz, 2 H, CH2), 4.27 (q, J = 7.2
Hz, 2 H, OCH2), 6.57 (m, 2 H, 2 × CH), 8.20 (br s, 1 H, NH).
MS (EI, 70 eV): m/z (%) = 153 (M+, 49), 138 (1), 94 (100), 80 (2).
Anal. Calcd for C8H11NO2 (153.181): C, 62.73; H, 7.24. Found: C,
63.04; H, 7.82.
Synthesis 2009, No. 2, 227–242 © Thieme Stuttgart · New York

238
E. Bellur et al.
PAPER
13C NMR (CDCl3), 75 MHz): d = 14.1, 14.5 (CH3), 22.6, 27.3, 29.3,
29.4, 29.47, 29.51, 29.7, 31.8 (CH2), 59.3 (OCH2), 110.5 (CH),
111.1 (C), 115.7 (CH), 140.0 (C), 165.5 (O=C–O).
MS (EI, 70 eV): m/z (%) = 265 (M+, 64), 236 (8), 220 (5), 192 (52),
166 (98), 154 (22), 138 (6), 124 (37), 120 (17), 94 (100).
HRMS (EI, 70 eV): m/z calcd for C16H27NO2: 265.20422 [M+];
found: 265.2042 2 ppm.
(silica gel, n-hexane–EtOAc, 50:1 → 1:1) as a light brown oil
(0.091 g, 41%).
IR (neat): 3327 (s), 2962 (s), 2928 (s), 2875 (m), 2863 (w), 1727
(m), 1701 (s), 1672 (s), 1576 (m), 1501 (m), 1456 (m), 1438 (m),
1402 (w), 1371 (w), 1329 (w), 1299 (w), 1271 (m), 1198 (m), 1167
(s), 1122 (m), 1093 (m), 1028 (m), 889 (w), 733 cm–1 (m).
1H NMR (CDCl3, 300 MHz): d = 1.22–1.44 (m, 7 H, CH3, 2 × CH2),
1.55–1.80 (m, 4 H, 2 × CH2), 2.92 (t, J = 7.2 Hz, 2 H, CH2), 3.53 (t,
J = 6.6 Hz, 2 H, CH2Cl), 4.26 (q, J = 7.2 Hz, 2 H, OCH2), 6.56 (d,
J = 2.7 Hz, 1 H, CH), 6.58 (d, J = 2.7 Hz, 1 H, CH), 8.23 (br s, 1 H,
NH).
Anal. Calcd for C16H27NO2 (265.395): C, 72.41; H, 10.25. Found:
C, 72.59; H, 10.60.
Ethyl 2-Decyl-1H-pyrrole-3-carboxylate (4k)
Route 1: Starting with 3o (0.130 g, 0.4 mmol) and Me3SiOTf (0.085
g, 0.4 mmol) in CH2Cl2 (7 mL), 4k was isolated after chromatogra-
phy (silica gel, n-hexane–EtOAc, 50:1 → 3:1) as a light brown oil
(0.061 g, 57%).
13C NMR (CDCl3, 75 MHz): d = 14.2 (CH3), 26.5, 27.1, 28.5, 30.4,
31.6 (CH2), 44.4 (CH2Cl), 59.2 (OCH2), 110.5 (CH), 110.8 (C),
115.8 (CH), 140.1 (C), 165.7 (O=C–O).
MS (EI, 70 eV): m/z (%) = 257 (M+, 11), 228 (6), 222 (8), 212 (10),
Route 2: Starting with 3p (0.300 g, 0.81 mmol) and Me3SiOTf
(0.180 g, 0.81 mmol) in CH2Cl2 (15 mL), 4k was isolated after chro-
matography (silica gel, n-hexane–EtOAc, 50:1 → 3:1) as a light
brown oil (0.122 g, 54%).
184 (37), 149 (52), 135 (24), 121 (100).
Anal. Calcd for C13H20NO2Cl (257.75): C, 60.58; H, 7.82. Found:
C, 60.42; H, 7.96.
IR (neat): 3369 (s), 2946 (s), 2925 (s), 2854 (s), 1676 (s), 1574 (w),
1463 (s), 1396 (w), 1371 (m), 1330 (m), 1300 (m), 1258 (m), 1192
(s), 1183 (s), 1130 (s), 1034 (m), 721 cm–1 (m).
1H NMR (CDCl3, 300 MHz): d = 0.88 (t, J = 7.2 Hz, 3 H, CH3),
1.20–1.36 (m, 17 H, CH3, 7 × CH2), 1.50–1.66 (m, 2 H, CH2), 2.94
(t, J = 7.8 Hz, 2 H, CH2), 4.27 (q, J = 7.2 Hz, 2 H, OCH2), 6.57 (d,
J = 2.7 Hz, 2 H, 2 × CH), 8.16 (br s, 1 H, NH).
13C NMR (CDCl3), 75 MHz): d = 14.1, 14.5 (CH3), 22.6, 27.3, 29.3,
29.41, 29.46, 29.52, 29.61, 31.2, 31.8 (CH2), 59.3 (OCH2), 110.5
(CH), 111.2 (C), 115.6 (CH), 140.0 (C), 165.5 (O=C–O).
MS (EI, 70 eV): m/z (%) = 279 (M+, 55), 250 (5), 234 (3), 206 (42),
192 (7), 166 (100), 138 (6), 120 (12), 94 (98).
HRMS (EI, 70 eV): m/z calcd for C17H29NO2: 279.2198 [M+];
found: 279.2198 2 ppm.
Ethyl 2-(7-Chloroheptyl)-1H-pyrrole-3-carboxylate (4n)
Starting with 3u (0.300 g, 0.8 mmol) and Me3SiOTf (0.183 g, 0.8
mmol) in CH2Cl2 (15 mL), 4n was isolated after chromatography
(silica gel, n-hexane–EtOAc, 50:1 → 1:1) as a light brown oil
(0.105 g, 47%).
IR (neat): 3326 (s), 2958 (s), 2926 (s), 2872 (m), 2856 (w), 1726
(m), 1703 (s), 1675 (s), 1573 (m), 1497 (m), 1461 (m), 1444 (m),
1400 (w), 1369 (w), 1335 (w), 1303 (w), 1269 (m), 1204 (m), 1164
(s), 1118 (m), 1092 (m), 1031 (m), 894 (w), 736 cm–1 (m).
1H NMR (CDCl3, 300 MHz): d = 1.21–1.45 (m, 9 H, CH3, 3 × CH2),
1.50–1.73 (m, 4 H, 2 × CH2), 2.91 (t, J = 7.2 Hz, 2 H, CH2), 3.53 (t,
J = 6.6 Hz, 2 H, CH2Cl), 4.26 (q, J = 7.2 Hz, 2 H, OCH2), 6.56 (d,
J = 2.7 Hz, 1 H, CH), 6.58 (d, J = 2.7 Hz, 1 H, CH), 8.22 (br s, 1 H,
NH).
13C NMR (CDCl3, 75 MHz): d = 14.3 (CH3), 26.7, 27.2, 28.6, 29.2,
30.6, 31.8 (CH2), 44.6 (CH2Cl), 59.3 (OCH2), 110.5 (CH), 110.9
(C), 115.9 (CH), 140.2 (C), 165.9 (O=C–O).
MS (EI, 70 eV): m/z (%) = 271 (M+, 12), 242 (8), 236 (6), 226 (6),
198 (35), 163 (52), 149 (12), 135 (100).
Ethyl 2-Undecyl-1H-pyrrole-3-carboxylate (4l)
Route 1: Starting with 3q (0.130 g, 0.4 mmol) and Me3SiOTf
(0.081 g, 0.4 mmol) in CH2Cl2 (5 mL), 4l was isolated after chro-
matography (silica gel, n-hexane–EtOAc, 50:1 → 5:1) as a light
brown oil (0.060 g, 57%).
Anal. Calcd for C14H22NO2Cl (271.78): C, 61.87; H, 8.16. Found:
C, 61.68; H, 8.28.
Route 2: Starting with 3r (0.400 g, 1.04 mmol) and Me3SiOTf
(0.231 g, 1.04 mmol) in CH2Cl2 (15 mL), 4l was isolated after chro-
matography (silica gel, n-hexane–EtOAc, 50:1 → 5:1) as a light
brown oil (0.171 g, 56%).
1-(2-Methyl-1H-pyrrol-3-yl)ethanone (4o)
Method A: Starting with 3v (0.100 g, 0.5 mmol) and TFA (0.36
mL, 4.7 mmol) in CH2Cl2 (10 mL), 4o was isolated after chroma-
tography (silica gel, n-hexane–EtOAc, 50:1 → 1:1) as a light yel-
low solid (0.039 g, 68%).
IR (neat): 3377 (m), 2956 (s), 2926 (s), 2854 (s), 1676 (s), 1463 (s),
1371 (w), 1330 (w), 1300 (w), 1257 (m), 1185 (m), 1183 (m), 1131
(s), 1032 (m), 721 cm–1 (w).
Method C: Starting with 3v (0.400 g, 1.86 mmol) in DMSO (5 mL),
4o¢ (0.023 g, 5%) and 4o (0.137 g 60%) were isolated after chroma-
tography (silica gel, n-hexane–EtOAc, 100:1 → 1:1) as light brown
oil and solid, respectively.
1H NMR (CDCl3, 300 MHz): d = 0.88 (t, J = 7.2 Hz, 3 H, CH3),
1.21–1.36 (m, 19 H, CH3, 8 × CH2), 1.48–1.58 (m, 2 H, CH2), 2.94
(t, J = 7.8 Hz, 2 H, CH2), 4.27 (q, J = 7.2 Hz, 2 H, OCH2), 6.57 (d,
J = 2.7 Hz, 2 H, 2 × CH), 8.14 (br s, 1 H, NH).
13C NMR (CDCl3), 75 MHz): d = 14.1, 14.5 (CH3), 22.7, 27.3, 29.3,
29.43, 29.46, 29.57, 29.60 (2 C), 31.2, 31.9 (CH2), 59.3 (OCH2),
110.5 (CH), 111.3 (C), 115.6 (CH), 139.9 (C), 165.5 (O=C–O).
MS (EI, 70 eV): m/z (%) = 293 (M+, 71), 264 (2), 220 (4), 166 (100),
138 (4), 120 (15), 94 (97).
HRMS (EI, 70 eV): m/z calcd for C18H31NO2: 293.2355 [M+];
found: 293.2355 2 ppm.
1-(1-(2,2-Diethoxyethyl)-2-methyl-1H-pyrrol-3-yl)ethanone
(4o¢)
IR (neat): 2977 (m), 2928 (m), 2921 (m), 2903 (m), 2899 (m), 2883
(m), 2750 (m), 2744 (m), 1733 (m), 1652 (s), 1597 (w), 1575 (w),
1558 (w), 1539 (s), 1505 (m), 1455 (m), 1435 (s), 1417 (m), 1372
(s), 1310 (m), 1266 (s), 1241 (s), 1219 (m), 1177 (m), 1151 (s), 1126
(s), 1065 (s), 952 (w), 919 (w), 902 (w), 723 (w), 684 (w), 675
cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 1.16 (t, J = 7.2 Hz, 6 H, 2 × CH3),
2.39 (s, 3 H, CH3), 2.57 (s, 3 H, CH3), 3.34–3.44 (m, 2 H, OCH2),
3.63–3.73 (m, 2 H, OCH2), 3.93 (d, J = 5.4 Hz, 2 H, NCH2), 4.54 (t,
Ethyl 2-(6-Chlorohexyl)-1H-pyrrole-3-carboxylate (4m)
Starting with 3t (0.300 g, 0.9 mmol) and Me3SiOTf (0.191 g, 0.9
mmol) in CH2Cl2 (15 mL), 4m was isolated after chromatography
Synthesis 2009, No. 2, 227–242 © Thieme Stuttgart · New York

PAPER
Staudinger–Aza-Wittig Reactions of 1,3-Dicarbonyl Compounds
239
J = 5.4 Hz, 1 H, OCH), 6.47 (d, J = 3.3 Hz, 1 H, CH), 6.55 (d,
J = 3.3 Hz, 1 H, CH).
1075 (w), 1032 (w), 880 (m), 792 (m), 743 (w), 712 (s), 702 (s), 672
(w), 612 cm–1 (w).
13C NMR (CDCl3, 75 MHz): d = 11.6, 15.2 (2 C), 29.7 (CH3), 49.7
(NCH2), 63.9 (2 C, OCH2), 102.0 (OCH), 110.0, 120.8 (CH), 121.2,
135.6 (C), 195.1 (C=O).
MS (EI, 70 eV): m/z (%) = 239 (M+, 31), 224 (2), 194 (6), 178 (2),
165 (18), 149 (10), 136 (5), 123 (14), 107 (60), 103 (100), 94 (14),
75 (83).
1H NMR (CDCl3, 300 MHz): d = 2.54 (s, 3 H, CH3), 6.40 (dd,
J = 3.0, 2.7 Hz, 1 H, CH), 6.55 (dd, J = 3.0, 2.4 Hz, 1 H, CH), 7.41–
7.51 (m, 3 H, 3 × CH of Ph), 7.78–7.81 (m, 2 H, 2 × CH of Ph), 9.06
(br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 13.7 (CH3), 112.5, 115.6 (CH),
119.6 (C), 128.0 (2 C), 129.0 (2 C), 131.1 (CH of Ph), 136.7 (C of
Ph), 140.6 (C), 192.8 (C=O).
HRMS (ESI): m/z calcd for C13H21NO3 [M+]: 239.15214; found:
239.15119.
MS (EI, 70 eV): m/z (%) = 185 (M+, 73), 170 (3), 107 (100), 80 (13),
77 (24).
1-(2-Methyl-1H-pyrrol-3-yl)ethanone (4o)
Mp 75 °C.
HRMS (ESI): m/z calcd for C12H11NO [M+]: 185.08406; found:
185.08483.
IR (KBr): 3211 (s), 3110 (s), 3021 (m), 2981 (w), 2962 (m), 2926
(m), 2843 (w), 1636 (s), 1569 (s), 1491 (s), 1465 (s), 1402 (s), 1364
(s), 1333 (w), 1279 (m), 944 (m), 892 (m), 858 (w), 799 (w), 775
(w), 733 (m), 677 (w), 636 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 2.43 (s, 3 H, CH3), 2.55 (s, 3 H,
CH3), 6.52–6.54 (m, 1 H, CH), 6.57–6.59 (m, 1 H, CH), 8.52 (br s,
1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 13.8, 28.3 (CH3), 110.5, 115.9
(CH), 120.5, 135.4 (C), 195.8 (C=O).
MS (EI, 70 eV): m/z (%) = 123 (M+, 44), 107 (100), 94 (3), 80 (25),
66 (2), 43 (11).
(2-Methoxyphenyl)(2-methyl-1H-pyrrol-3-yl)methanone (4s)
Starting with 3y (0.120 g, 0.1 mmol) and TFA (0.32 mL, 4.3 mmol)
in CH2Cl2 (6.4 mL), 4s was isolated after chromatography (silica
gel, n-hexane–EtOAc, 50:1 → 1:1) as a light yellow oil (0.70 g,
79%).
IR (KBr): 3270 (w), 3054 (w), 2926 (w), 1598 (m), 1498 (s), 1283
(s), 1021 (w), 735 cm–1 (s).
1H NMR (CDCl3, 250 MHz): d = 2.43 (s, 3 H, CH3), 3.72 (s, 3 H,
OCH3), 6.17–6.19 (m, 1 H, CHpy), 6.43–6.45 (m, 1 H, CHpy), 6.88–
6.94 (m, 2 H, CHAr), 7.24 (dd, 3J = 7.7 Hz, 4J = 2.0 Hz, 1 H, CHAr),
8.35 (dd, 3J = 7.4 Hz, 4J = 2.0 Hz, 1 H, CHAr), 8.35 (br s, 1 H, NH).
13C NMR (CDCl3, 62 MHz): d = 13.8 (CH3), 55.7 (OCH3), 111.3
(CHpy), 112.5 (CHAr), 120.2 (CHAr), 121.1 (Cpy), 128.3, 128.7,
130.5 (CAr), 136.4 (CPy), 156.5 (CAr), 192.1 (C = O).
Anal. Calcd for C7H9NO (123.155): C, 68.27; H, 7.37. Found: C,
68.12; H, 7.15.
1-(2-Ethyl-1H-pyrrol-3-yl)propan-1-one (4p)
Starting with 3w (0.300 g, 1.2 mmol) and TFA (0.96 mL, 12.3
mmol) in CH2Cl2 (15 mL), 4p was isolated after chromatography
(silica gel, n-hexane–EtOAc, 50:1 → 1:1) as a light yellow solid
(0.130 g, 70%).
Anal. Calcd for C13H13NO2 (215.25): C, 72.54; H, 6.09. Found: C,
72.84; H, 6.22.
(2-Chlorophenyl)(2-methyl-1H-pyrrol-3-yl)methanone (4t)
Starting with 3w (0.216 g, 0.8 mmol) and TFA (0.57 mL, 7.7 mmol)
in CH2Cl2 (12 mL), 4t was isolated after chromatography (silica gel,
n-hexane–EtOAc, 50:1 → 1:1) as a light yellow oil (0.100 g, 63%).
IR (KBr): 3213 (s), 3112 (s), 3023 (m), 2978 (m), 2959 (m), 2927
(m), 2851 (w), 1646 (s), 1571 (m), 1493 (s), 1475 (s), 1412 (s), 1367
(s), 1331 (w), 1282 (m), 1220 (m), 1150 (w), 954 (m), 902 (w), 885
(m), 796 (m), 739 (m), 675 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 1.18 (t, J = 7.2 Hz, 3 H, CH3),
1.20 (t, J = 7.2 Hz, 3 H, CH3), 2.70 (q, J = 7.2 Hz, 2 H, CH2), 2.97
(q, J = 7.2 Hz, 2 H, CH2), 6.38–6.41 (m, 1 H, CH), 6.45–6.49 (m, 1
H, CH), 8.27 (br s, 1 H, NH).
IR (neat): 3350 (w), 2923 (w), 2826 (w), 1674 (m), 1642 (s), 1264
(s), 1072 (w), 749 cm–1 (s).
1H NMR (CDCl3, 250 MHz): d = 2.44 (s, 3 H, CH3), 6.15 (m, 1 H,
CHpy), 6.48 (m, 1 H, CHpy), 7.25–7.28 (m, 2 H, CHAr), 7.30–7.33
(m, 1 H, CHAr), 7.35 (br m, 2 H, CHAr), 8.28 (br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 10.1, 13.8, (CH3), 20.2, 35.4
13C NMR (CDCl3, 62 MHz): d = 13.8 (CH3), 112.4, 115.9 (CHpy),
120.4 (CPy), 126.4, 128.3, 129.8, 130.1 (CHAr), 137.6 (CAr), 139.2
(CAr), 140.9 (CAr), 190.6 (C=O).
(CH2), 110.7, 115.8 (CH), 119.8, 146.1 (C), 199.4 (C=O).
MS (EI, 70 eV): m/z (%) = 151 (M+, 51), 122 (3), 107 (100), 94 (16),
80 (17), 66 (5), 57 (7).
Anal. Calcd for C12H10NOCl (219.66): C, 65.62; H, 4.59. Found: C,
65.88; H, 4.76.
Anal. Calcd for C9H13NO (151.206): C, 71.49; H, 8.67. Found: C,
71.22; H, 8.35.
1,5,6,7-Tetrahydro-4H-indol-4-one (7a)
Method A: Starting with 6a (0.070 g, 0.3 mmol) and TFA (0.24
mL, 3.1 mmol) in CH2Cl2 (5 mL), 7a was isolated after chromatog-
raphy (silica gel, n-hexane–EtOAc, 50:1 → EtOAc) as a slightly
light yellow solid (0.040 g, 95%).
(2-Methyl-1H-pyrrol-3-yl)(phenyl)methanone (4r)
Method A: Starting with 3x (0.050 g, 0.2 mmol) and TFA (0.14
mL, 1.8 mmol) in CH2Cl2 (3 mL), 4r was isolated after chromatog-
raphy (silica gel, n-hexane–EtOAc, 50:1 → 1:1) as a slightly light
yellow solid (0.027 g, 82%).
Method C: Starting with 6a (0.300 g, 1.32 mmol) in DMSO (10
mL), 7a was isolated after chromatography (silica gel, n-hexane–
EtOAc, 50:1 → EtOAc) as a light brown oil (0.126 g, 71%).
Method B: Starting with 3x (0.050 g, 0.2 mmol) and Me3SiOTf
(0.040 g, 0.2 mmol) in CH2Cl2 (3 mL), 4r was isolated after chro-
matography (silica gel, n-hexane–EtOAc, 50:1 → 1:1) as a slightly
light yellow solid (0.026 g, 79%).
IR (KBr): 3183 (w), 3105 (s), 2949 (s), 2889 (w), 2846 (w), 1683
(w), 1622 (s), 1493 (s), 1477 (s), 1310 (w), 1197 (w), 1146 (w), 893
(w), 854 (w), 804 (w), 705 cm–1 (w).
1H NMR (CDCl3–DMSO-d6, 1:1, 300 MHz): d = 2.12 (quint,
J = 6.3 Hz, 2 H, CH2), 2.44 (t, J = 6.3 Hz, 2 H, CH2), 2.81 (t, J = 6.3
Hz, 2 H, CH2), 6.44 (m, 1 H, CH), 6.64 (m, 1 H, CH), 10.71 (br s, 1
H, NH).
Method C: Starting with 3x (0.100 g, 0.4 mmol) in DMSO (5 mL),
4r was isolated after chromatography (silica gel, n-hexane–
EtOAc, 50:1 → 1:1) as a light brown solid (0.048 g, 72%).
IR (KBr): 3232 (w), 2924 (w), 1608 (s), 1561 (m), 1446 (s), 1367
(m), 1340 (w), 1277 (m), 1212 (w), 1180 (w), 1148 (w), 1101 (w),
Synthesis 2009, No. 2, 227–242 © Thieme Stuttgart · New York

240
E. Bellur et al.
PAPER
13C NMR (CDCl3–DMSO-d6, 1:1, 75 MHz): d = 22.1, 23.5, 37.4
1-(2,2-Diethoxyethyl)-2,5-dimethyl-1H-pyrrole (9)
(CH2), 104.4, 118.2 (CH), 119.4, 143.5 (C), 194.0 (C=O).
Starting with acetonylacetone (8) (0.21 mL, 1.8 mmol), 2-azido-
1,1-diethoxyethane (2a) (0.335 g, 2.1 mmol) and Ph3P (0.708 g, 2.7
mmol) in THF (10 mL), 9 was isolated after chromatography (silica
gel, n-hexane–EtOAc, 100:1 → 10:1) as a slightly light yellow oil
(0.353 g, 93%).
MS (EI, 70 eV): m/z (%) = 135 (M+, 29), 106 (29), 103 (100), 79
(30).
HRMS (ESI): m/z calcd for C8H9NO [M+]: 135.06841; found:
135.06852.
IR (neat): 2976 (s), 2925 (s), 2901 (s), 1521 (w), 1447 (m), 1409 (s),
1383 (m), 1303 (m), 1130 (s), 1067 (s), 1019 (m), 752 cm–1 (s).
1H NMR (CDCl3, 300 MHz): d = 1.16 (t, J = 7.2 Hz, 6 H, 2 × CH3),
2.24 (s, 6 H, 2 × CH3), 3.29–3.39 (m, 2 H, OCH2), 3.61–3.71 (m, 2
H, OCH2), 3.87 (d, J = 5.4 Hz, 2 H, NCH2), 4.49 (t, J = 5.4 Hz, 1 H,
OCH), 5.75 (s, 2 H, 2 × CH).
6,6-Dimethyl-1,5,6,7-tetrahydro-4H-indol-4-one (7b)
Starting with 6b (0.090 g, 0.4 mmol) and TFA (0.27 mL, 3.5 mmol)
in CH2Cl2 (7 mL), 7b was isolated after chromatography (silica gel,
n-hexane–EtOAc, 50:1 → EtOAc) as a slightly light yellow solid
(0.034 g, 60%).
IR (KBr): 3278 (w), 2962 (w), 1626 (s), 1472 (m), 1412 (m), 1203
(s), 1173 cm–1 (s).
1H NMR (CDCl3 + DMSO-d6, 300 MHz): d = 1.12 (s, 6 H,
2 × CH3), 2.37 (s, 2 H, CH2), 2.68 (s, 2 H, CH2), 6.56 (m, 1 H, CH),
6.68 (m, 1 H, CH), 8.50 (br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 11.7 (2 C), 14.2 (2 C, CH3), 46.4
(NCH2), 62.9 (2 × OCH2), 101.8 (OCH), 104.3 (2 × CH), 127.1
(2 × C).
MS (EI, 70 eV): m/z (%) = 211 (M+, 58), 166 (21), 138 (10), 122
(12), 107 (39), 103 (100), 76 (94).
13C NMR (CDCl3 + DMSO-d6, 75 MHz): d = 28.6 (2 × CH3), 35.9
(C), 36.9, 52.0 (CH2), 105.8, 118.7 (CH), 119.2, 142.5 (C), 194.1
(C=O).
MS (EI, 70 eV): m/z (%) = 163 (M+, 11), 106 (20), 95 (10), 83 (8),
79 (12), 70 (100).
HRMS (ESI): m/z calcd for C10H13NO [M+]: 163.09971; found:
163.09984.
3-Azido-1,1-diethoxypropane (10)
Sodium azide (9.752 g, 150 mmol) and potassium iodide (1.669 g,
10 mmol) were added to 3-chloropropionaldehyde diethyl acetal
(16.8 mL, 100 mmol) in DMSO (100 mL) at r.t. The reaction mix-
ture was heated to 90 °C and stirred for 72 h at 90 °C. After cooling
to r.t., H2O (200 mL) and Et2O (200 mL) were added, the organic
layer was separated and the aqueous layer was repeatedly extracted
with Et2O (3 × 200 mL). The combined organic extracts were dried
over Na2SO4, filtered, and the filtrate was concentrated to dryness
in vacuo. Product 10 was isolated without further purification as a
slightly light yellow oil (15.271 g, 88%).
6-Methyl-1,5,6,7-tetrahydro-4H-indol-4-one (7c)
Starting with 6c (0.300 g, 1.2 mmol) and TFA (0.96 mL, 12.4
mmol) in CH2Cl2 (15 mL), 7c was isolated after chromatography
(silica gel, n-hexane–EtOAc, 30:1 → EtOAc) as a slightly light yel-
low solid (0.139 g, 75%).
IR (neat): 3415 (br), 2998 (w), 2950 (w), 2099 (m), 1653 (m), 1441
(m), 1411 (m), 1130 (m), 1062 (s), 1021 (s), 953 (m), 709 (w), 669
cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 1.22 (t, J = 7.2 Hz, 6 H, 2 × CH3),
1.89 (dq, J = 5.7, 1.2 Hz, 2 H, CH2), 3.38 (t, J = 6.9 Hz, 2 H,
CH2N3), 3.47–3.57 (m, 2 H, OCH2), 3.62–3.73 (m, 2 H, OCH2),
4.60 (t, J = 5.7 Hz, 1 H, OCH).
IR (KBr): 3257 (w), 3070 (w), 2959 (m), 2879 (w), 1624 (s), 1475
(m), 1414 (m), 1204 (s), 1175 cm–1 (s).
1H NMR (CDCl3 + DMSO-d6, 300 MHz): d = 1.02–1.12 (m, 3 H,
CH3), 2.22–2.86 (m, 5 H, 2 × CH2, CH), 6.58 (m, 1 H, CH), 6.69 (m,
1 H, CH), 8.53 (br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 14.7 (2 C, CH3), 32.7 (CH2), 46.9
13C NMR (CDCl3 + DMSO-d6, 75 MHz): d = 20.8 (CH3), 30.6
(CH), 33.4, 47.2 (CH2), 106.1, 118.5 (CH), 119.3, 143.1 (C), 194.1
(C=O).
(CH2N3), 61.2 (2 C, OCH2), 99.9 (CH).
MS (EI, 70 eV): m/z (%) = 127 ([M – OEt]+, 29), 116 (11), 103 (81),
73 (59), 57 (13), 45 (93), 28 (100).
MS (EI, 70 eV): m/z (%) = 149 (M+, 15), 108 (24), 93 (7), 79 (22),
70 (100).
3-[(3,3-Diethoxypropyl)amino]-1-phenylbut-2-en-1-one (11)
The reaction was carried by application of the procedure given for
the synthesis of products 3. Starting with benzoylacetone (1u)
(0.487 g, 3.0 mmol), 10 (0.624 g, 3.6 mmol) and Ph3P (1.180 g, 4.5
mmol) in THF (15 mL), 11 was isolated after chromatography (sil-
ica gel, n-hexane–EtOAc, 50:1 → 3:1) as a light yellow oil (0.805
g, 95%).
Anal. Calcd for C9H11NO (149.190): C, 72.46; H, 7.43. Found: C,
72.02; H, 7.73.
6-Phenyl-1,5,6,7-tetrahydro-4H-indol-4-one (7d)
Starting with 6d (0.300 g, 1.0 mmol) and TFA (0.76 mL, 9.9 mmol)
in CH2Cl2 (15 mL), 7d was isolated after chromatography (silica
gel, n-hexane–EtOAc, 30:1 → EtOAc) as a light yellow solid (0.153
g, 73%).
IR (neat): 3463 (br), 3061 (w), 2974 (m), 2929 (m), 2882 (m), 1601
(s), 1547 (s), 1442 (m), 1379 (m), 1317 (s), 1299 (s), 1226 (w), 1127
(s), 1064 (s), 809 (w), 739 (m), 688 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 1.22 (t, J = 7.2 Hz, 6 H, 2 × CH3),
1.96 (dq, J = 5.7, 1.2 Hz, 2 H, CH2), 2.08 (s, 3 H, CH3), 4.43 (dt,
J = 6.9, 6.3 Hz, 2 H, NCH2), 3.47–3.58 (m, 2 H, OCH2), 3.63–3.73
(m, 2 H, OCH2), 4.62 (t, J = 5.4 Hz, 1 H, OCH), 5.66 (s, 1 H,
CH=C), 7.36–7.42 (m, 3 H, 3 × CH of Ph), 7.83–7.86 (m, 2 H,
2 × CH of Ph), 11.44 (br s, 1 H, NH).
13C NMR (CDCl3, 75 MHz): d = 14.6 (2 C), 18.4 (CH3), 33.5 (CH2),
38.3 (NCH2), 61.0 (2 C, OCH2), 91.2 (HC=C–N), 99.9 (OCH),
126.1 (2 C), 127.4 (2 C), 129.6 (CH of Ph), 139.8 (C of Ph), 164.1
(N–C=CH), 186.5 (C=O).
IR (KBr): 3285 (m), 3067 (m), 2971 (m), 2886 (m), 1625 (s), 1471
(m), 1410 (m), 1199 (w), 1171 (m), 759 (w), 705 cm–1 (w).
1H NMR (CDCl3– DMSO-d6, 1:1, 300 MHz): d = 2.65–3.15 (m, 4
H, 2 × CH2), 3.44–3.64 (m, 1 H, CHPh), 6.53 (m, 1 H, CH), 6.63 (m,
1 H, NCH), 7.21–7.38 (m, 5 H, 5 × CH of Ph), 8.76 (br s, 1 H, NH).
13C NMR (CDCl3– DMSO-d6, 1:1, 75 MHz): d = 35.1 (CH2), 42.3
(CHPh), 45.2 (CH2), 106.4, 118.3 (CH), 119.1, 143.0 (C), 126.3 (2
C), 126.8, 128.9 (2 C, CH of Ph), 143.9 (C of Ph), 194.0 (C=O).
MS (EI, 70 eV): m/z (%) = 211 (M+, 21), 170 (5), 132 (100), 107
(21), 93 (5), 91 (19), 79 (26), 77 (12).
Anal. Calcd for C14H13NO (211.259): C, 79.59; H, 6.20. Found: C,
79.17; H, 6.03.
Synthesis 2009, No. 2, 227–242 © Thieme Stuttgart · New York

PAPER
Staudinger–Aza-Wittig Reactions of 1,3-Dicarbonyl Compounds
241
MS (EI, 70eV): m/z (%) = 291 (M+, 60), 262 (10), 146 (10), 216
(32), 201 (8), 188 (42), 174 (83), 160 (4), 145 (12), 131 (15), 105
(100), 103 (17), 91 (38), 77 (37).
(3) For pyrrole syntheses: (a) Huisgen, R. Angew. Chem., Int.
Ed. Engl. 1967, 2, 565. (b) Huisgen, R.; Gotthard, H.;
Bayer, H. O.; Schäfer, F. C. Chem. Ber. 1970, 103, 2611.
(c) Barnard, G. F.; Itoh, R.; Hohberger, L.; Shemin, D.
J. Biol. Chem. 1977, 252, 8965. (d) Chiu, P.-K.; Lui, K.-H.;
Maini, P. N.; Sammes, M. P. J. Chem. Soc., Chem. Commun.
1987, 109. (e) Barton, D. H. R.; Kervagoret, J.; Zard, S. Z.
Tetrahedron 1990, 46, 7587. (f) Roskamp, E. J.; Dragovich,
P. S.; Hartung, J. B.; Pederson, S. F. J. Org. Chem. 1989, 54,
4736. (g) Tang, J.; Verkade, J. G. J. Org. Chem. 1994, 59,
7793. (h) De Kimpe, N.; Tehrani, K. A.; Stevens, C.; De
Cooman, P. Tetrahedron 1997, 53, 3693. (i) Alberala, A.;
Ortega, A. G.; Sádaba, M. L.; Snudo, C. Tetrahedron 1999,
55, 6555.
Anal. Calcd for C17H25NO3 (291.390): C, 70.07; H, 8.65. Found: C,
70.03; H, 8.73.
(2-Methylpyridin-3-yl)(phenyl)methanone (12)
The reaction was carried by application of the procedures given for
the synthesis of products 3 and 4 (method A). Starting with 11
(0.146 g, 0.5 mmol) and TFA (0.4 mL, 5.0 mmol) in CH2Cl2 (3 mL)
(0–20 °C), 12 was isolated after chromatography (silica gel, n-hex-
ane–EtOAc, 50:1 → EtOAc) as a light yellow solid (0.095 g, 96%).
IR (KBr): 3004 (w), 1721 (s), 1667 (s), 1616 (m), 1456 (m), 1414
(w), 1382 (w), 1283 (s), 1198 (s), 1131 (s), 1070 (m), 965 (m), 898
(w), 822 (s), 706 (m), 638 (m), 574 (w), 545 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 2.76 (s, 3 H, CH3), 7.55 (t, J = 7.5
Hz, 2 H, 2 × CH), 7.69–7.79 (m, 4 H, 4 × CH), 8.16 (d, J = 7.5 Hz,
1 H, CH), 8.96 (d, J = 4.8 Hz, 1 H, CH).
13C NMR (CDCl3, 75 MHz): d = 19.2 (CH3), 123.1, 129.2 (2 C),
130.0 (2 C), 134.8 (CH), 135.4, 136.7 (C), 141.7, 144.7 (CH), 154.1
(C), 193.0 (C=O).
MS (EI, 70 eV): m/z (%) = 197 (M+, 100), 182 (3), 120 (12), 105
(50), 92 (24), 77 (57).
HRMS (ESI): m/z calcd for C13H11NO [M+]: 197.0841; found:
197.0822.
(4) For other pyrrole syntheses: (a) Grigg, R.; Savic, V. Chem.
Commun. 2000, 873. (b) Trofimov, B. A.; Tarasova, O. A.;
Mikhaleva, A. I.; Kalinina, N. A.; Sinegovskaya, L. M.;
Henkelmann, J. Synthesis 2000, 1585. (c) Almerico, A. M.;
Montalbano, A.; Diana, P.; Barraja, P.; Lauria, A.;
Cirrincione, G.; Dattolo, G. ARKIVOC 2001, (vi), 129.
(d) Trofimov, B. A.; Markova, M. V.; Morozova, L. V.;
Mikhaleva, A. I. ARKIVOC 2001, (ix), 24. (e) Nair, V.;
Vinod, A. U.; Rajesh, C. J. Org. Chem. 2001, 66, 4427.
(f) Ranu, B. C.; Hajra, A. Tetrahedron 2001, 57, 4767.
(g) Lagu, B.; Pan, M.; Wachter, M. P. Tetrahedron Lett.
2001, 42, 6027. (h) Quiclet-Sire, B.; Wendeborn, F.; Zard,
S. Z. Chem. Commun. 2002, 2214. (i) Demir, A. S.;
Akhmedov, I. M.; Sesenoglu, Tetrahedron 2002, 58, 9793.
(j) Yoshida, M.; Kitamura, M.; Narasaka, K. Bull. Chem.
Soc. Jpn. 2003, 76, 2003. (k) Knight, D. W.; Sharland, C.
M. Synlett 2003, 2258. (l) Yu, M.; Pagenkopf, B. L. Org.
Lett. 2003, 5, 5099. (m) Dhawan, R.; Arndtsen, B. A. J. Am.
Chem. Soc. 2004, 126, 468. (n) Flögel, O.; Reissig, H.-U.
Synlett 2004, 895. (o) Song, Z.; Reiner, J.; Zhao, K.
Tetrahedron Lett. 2004, 45, 3953. (p) Chien, T.-C.; Meade,
E. A.; Hinkley, J. M.; Townsend, L. B. Org. Lett. 2004, 6,
2857. (q) Ramanathan, B.; Keith, A. J.; Armstrong, D.;
Odom, A. L. Org. Lett. 2004, 6, 2957. (r) Trofimov, B. A.;
Zaitsev, A. B.; Schmidt, E. Y.; Vasil’tsov, A. M.;
UV/Vis (MeCN): λmax (log ε) = 251 nm (3.90).
Acknowledgement
Financial support by the state of Pakistan (HEC scholarships for
I.H. and for M.A.Y.) and by the DAAD (scholarship for A.S.A.M.)
is gratefully acknowledged.
References
(1) For pyrrole natural products: (a) Falk, H. The Chemistry of
Linear Oligopyrroles and Bile Pigments; Springer-Verlag:
Wien, 1989, 355. (b) Montforts, F.-P.; Schwartz, U. M.
Angew. Chem., Int. Ed. Engl. 1985, 24, 775; Angew. Chem.
1985, 97, 767. (c) Dutton, C. J.; Fookes, C. J. R.; Battersby,
A. R. J. Chem. Soc., Chem. Commun. 1983, 1237.
Mikhaleva, A. I.; Ushakov, I. A.; Vashchenko, A. V.;
Zorina, N. V. Tetrahedron Lett. 2004, 45, 3789.
(s) Agarwal, S.; Knölker, H.-J. Org. Biomol. Chem. 2004, 2,
3060. (t) Dieltiens, N.; Stevens, C. V.; De Vos, D.; Allaert,
B.; Drozdzak, R.; Verpoort, F. Tetrahedron Lett. 2004, 45,
8995. (u) Dieltiens, N.; Stevens, C. V.; Allaert, B.; Verpoort,
F. ARKIVOC 2005, (i), 92. (v) Schmidt, E. Y.; Mikhaleva,
A. I.; Vasil’tsov, A. M.; Zaitsev Zorina, A. B. N. V.
ARKIVOC 2005, (vii), 11. (w) Tehrani, K. A.; Borremans,
D.; De Kimpe, N. Tetrahedron 1999, 55, 4133.
(d) Stork, G.; Nakahara, Y.; Nakahara, Y.; Greenlee, W. J.
J. Am. Chem. Soc. 1978, 100, 7775. (e) Stork, G.;
Nakamura, E. J. Am. Chem. Soc. 1983, 105, 5510.
(f) Bickmeyer, U.; Drechsler, C.; Köck, M.; Assmann, M.
Toxicon 2004, 44, 45. (g) Lindel, T.; Breckle, G.;
(x) Kesteleyn, B.; Alonso, E. R.; Stevens, C.; Dejaegher, Y.;
Peristeropoulou, M.; Tuyen, N. V.; Kulinkovich, O.; De
Kimpe, N. Tetrahedron 1999, 55, 4153.
Hochgürtel, M.; Volk, C.; Grube, A.; Köck, M. Tetrahedron
Lett. 2004, 45, 8149. (h) Feldman, K. S. ARKIVOC 2003,
(vi), 179. (i) Holub, J. M.; O’Toole-Colin, K.; Getzel, A.;
Argenti, A.; Evans, M. A.; Smith, D. C.; Dalglish, G. A.;
Rifat, S.; Wilson, D. L.; Taylor, B. M.; Miott, U.; Glersaye,
J.; Lam, K. S.; McCranor, B. J.; Berkowitz, J. D.; Miller, R.
B.; Lukens, J. R.; Krumpe, K.; Gupton, J. T.; Burnham, B. S.
Molecules 2004, 9, 135; and references cited therein.
(2) Books for pyrrole syntheses: (a) Eicher, T.; Hauptmann, S.
Chemie der Heterocyclen; Thieme Verlag: Stuttgart, 1994,
94. (b) Sundberg, R. J. In Comprehensive Heterocyclic
Chemistry, Vol. 4; Bird, C. W.; Cheeseman, G. W. H., Eds.;
Pergamon Press: Oxford, 1984, 331. (c) Gribble, G. W.
Comprehensive Heterocyclic Chemistry II, Vol. 2;
(5) Reviews of aza-Wittig reactions: (a) Eguchi, S.; Okano, T.;
Okawa, T. Recent Res. Dev. Org. Chem. 1997, 337; Chem.
Abstr. 1999, 130, 252510. (b) Fresneda, P. M.; Molina, P.
Synlett 2004, 1. (c) Eguchi, S. ARKIVOC 2005, (ii), 98.
(d) Palacios, F.; Alonso, C.; Aparicio, D.; Rubiales, G.;
de los Santos, J. M. Tetrahedron 2007, 63, 523.
(6) (a) Montforts, F.-P.; Schwartz, U. M.; Mai, G. Liebigs Ann.
Chem. 1990, 1037. (b) Gusar, N. I. Russ. Chem. Rev. 1991,
60, 146. (c) Eguchi, S.; Matsushita, Y.; Yamashita, K. Org.
Prep. Proced. Int. 1992, 24, 211. (d) Eguchi, S.; Okano, T.
J. Synth. Org. Chem. Jpn. 1993, 51, 203. (e) Molina, P.;
Viliplana, M. J. Synthesis 1994, 1197. (f) Wamhoff, H.;
Richard, G.; Stoelben, S. Adv. Heterocycl. Chem. 1995, 64,
159. (g) Ming-Wu, D.; Zhao-Jie, L. Chin. J. Org. Chem.
2001, 21, 1.
Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V., Eds.;
Elsevier: Oxford, 1996, 207. (d) Bean, G. P. Pyrroles;
Jones, R. A., Ed.; Wiley: New York, 1990, 105.
Synthesis 2009, No. 2, 227–242 © Thieme Stuttgart · New York

242
E. Bellur et al.
PAPER
(7) (a) Langer, P.; Freifeld, I. Chem. Commun. 2002, 2668.
(b) Freifeld, I.; Shojaei, H.; Langer, P. J. Org. Chem. 2006,
71, 4965.
(8) Bellur, E.; Görls, H.; Langer, P. J. Org. Chem. 2005, 70,
4751.
(11) (a) Bertschy, H.; Meunier, A.; Neier, R. Angew. Chem., Int.
Ed. Engl. 1990, 29, 777; Angew. Chem. 1990, 102, 828.
(b) Carboni, B.; Vaultier, M.; Carrie, R. Tetrahedron 1987,
43, 1799. (c) Chavan, S. P.; Subbarao, Y. T. Tetrahedron
Lett. 1999, 40, 5073.
(9) Bellur, E.; Langer, P. Tetrahedron Lett. 2006, 47, 2151.
(10) (a) Parr, R. W.; Reiss, J. A. Aust. J. Chem. 1984, 37, 389.
(b) Bridge, A. W.; Fenton, G.; Halley, F.; Hursthouse, M. B.;
Lehmann, C. W.; Lythgoe, D. J. J. Chem. Soc., Perkin Trans.
1 1993, 22, 2761. (c) Kascheres, A.; Schumacher, H. C.;
Rodrigues, R. A. F. J. Heterocycl. Chem. 1997, 34, 757.
(12) Bobbitt, J. M.; Kulkarni, C. L.; Dutta, C. P.; Kofod, H.;
Chiong, K. N. J. Org. Chem. 1978, 43, 3541.
Synthesis 2009, No. 2, 227–242 © Thieme Stuttgart · New York