Synthesis of annulated pyrroles: Condensation of aldose sugars, arylamines, and 1,3-diones using TBAB

Article abstract of DOI:10.1055/s-0030-1257973

Readily available tetrabutylammonium bromide (TBAB, 10 mol%), in the molten state, efficiently catalyzes the reaction of a variety of in situ generated enamines, from arylamines and 1,3-ketones, with aldose sugars under solvent-free conditions. The reaction proceeds rapidly and affords the corresponding protected annulated pyrrole derivatives in good to high yields (55-78%) after acetylation. The present methodology offers advantages such as excellent yields, a simple procedure, shorter reaction times, and milder conditions. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0030-1257973

3374
PAPER
Synthesis of Annulated Pyrroles: Condensation of Aldose Sugars, Arylamines,
and 1,3-Diones Using TBAB
Synthesisof
A
n
i
nulated
n
Pyrrole
s
gaiah Nagarapu,* Venkata Narasimhaji Cheemalapati, Shuklachary Karnakanti, Rajashaker Bantu
Organic Chemistry Division-II, Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, India
Fax +91(40)27193382; E-mail: nagarapu2@yahoo.co.in; E-mail: nagarapu@iict.res.in
Received 15 May 2010; revised 21 May 2010
Tetrabutylammonium bromide is an inexpensive and
Abstract: Readily available tetrabutylammonium bromide (TBAB,
10 mol%), in the molten state, efficiently catalyzes the reaction of a
variety of in situ generated enamines, from arylamines and 1,3-ke-
tones, with aldose sugars under solvent-free conditions. The reac-
readily available ionic liquid with inherent properties like
environmental compatibility, high selectivity, operational
simplicity, noncorrosive nature, and ease of reuse. It is,
tion proceeds rapidly and affords the corresponding protected therefore, of interest to examine the behavior of tetrabutyl-
annulated pyrrole derivatives in good to high yields (55–78%) after
ammonium bromide as a catalyst in the synthesis of annu-
acetylation. The present methodology offers advantages such as ex-
lated pyrrole derivatives. To the best of our knowledge,
cellent yields, a simple procedure, shorter reaction times, and mild-
the generality and applicability of tetrabutylammonium
er conditions.
bromide in the preparation of annulated pyrroles is not
Key words: aldose sugars, 1,3-diones, tetrabutylammonium bro-
mide, one-pot synthesis, shorter reaction times
known. In continuation of our program on the develop-
ment of novel methodologies in organic synthesis,10
a
general and practical method for the one-pot synthesis of
annulated pyrrole derivatives from unprotected sugar al-
doses and enamines catalyzed by molten tetrabutylammo-
nium bromide under solvent-free conditions has been
developed and is reported herein (Schemes 1 and 2).
Glycosylation of heterocyclic compounds that are rich in
biological activity is a field of increasing interest, for ex-
ample, the synthesis of various guanidine glycosides that
display improved biological properties (anti-inflammato-
ry and anti-HIV activity) with respect to the non-glycosy-
lated guanidine derivatives.1 In addition, the synthesis of
C-glycoconjugates is a current topic of research in medic-
inal chemistry due to the potent activity of various mole-
cules, such as anticancer and antiviral agents. In organic
synthesis, generally, carbohydrates are recognized as at-
tractive starting materials due to their easy availability,
multichirality, and well-defined stereochemistry.2
OH
O
ArNH2
2
O
O
OH
OH
O
TBAB
HO
HO
R
+
O
HO
N
R
OH
Ar
4
1
3a: R = Me
3b: R = OEt
Ac2O, DMAP
In the literature only one report3 for the synthesis of sugar-
annulated pyrrole derivatives using indium chloride is
available. The main disadvantage of this method is the
cost and toxicity of the catalyst. Therefore, the develop-
ment of a more practical and economical method for the
one-pot synthesis of annulated pyrroles is highly desir-
able.
1. TBAB
2. Ac2O, DMAP
O
(with no isolation of 4)
O
AcO
AcO
R
N
Ar
5
In recent years, tetrabutylammonium bromide has
emerged as a powerful Lewis acid catalyst, and allows
many useful organic transformations to be performed un-
der mild reaction conditions. Moreover, tetrabutylammo-
nium bromide is inexpensive, easy-to-handle, and is an
extremely useful homogeneous catalyst in various organic
transformations,4 such as conjugate addition of thiols to
electron-deficient alkenes,5 transthioacetalization of ace-
tals,6 synthesis of 2,4,5-trisubstituted imidazoles,7 tri-
methylsilylation of alcohols8 and the synthesis of aryl-
14H-dibenzo[a,j]xanthenes.9
Scheme 1
Initially, a pilot reaction was attempted using D-glucose
(1), aniline 2, and acetylacetone (3a) in the presence of
tetrabutylammonium bromide (10 mol%) without any sol-
vent. After 8 hours, the dihydroxy pyrrole derivative 4a
was isolated and converted into its acetyl derivative 5a in
75% overall yield (Table 1, entry 3) using acetic anhy-
dride with a catalytic amount of 4-(dimethylamino)pyri-
dine (DMAP). Increasing the amount of tetra-
butylammonium bromide (10–20 mol%) did not improve
the product yield to a considerable extent. Subsequently,
we also investigated the effect of various solvents on the
reaction rate as well as the yield of the products. Thus, 5a
was obtained in 39% yield in water, ~71% in ethanol, and
SYNTHESIS 2010, No. 19, pp 3374–3378
x
x.
x
x
.
2
0
1
0
Advanced online publication: 13.08.2010
DOI: 10.1055/s-0030-1257973; Art ID: Z12510SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Annulated Pyrroles
3375
Table 2 Tetrabutylammonium Bromide Catalyzed Synthesis of An-
nulated Pyrroles 5, 8, and 9 from Sugars and Enamines Followed by
Acetylationa
65% in ethanol–water (entries 1, 2, and 4). The reaction
was also studied with various catalysts such as tetrabuty-
lammonium iodide (entries 5–8), tetrabutylammonium
fluoride (entries 6–12), and tin(II) chloride (entries 13–
16) which resulted in 5a in lower yield. The formation of
compound 5a was evident from the appearance in its mass
spectrum of a peak at m/z 386 ([M + H]+), carbonyl
Entry Aldose ArNH2 2
1,3-Dione Productb Time Yieldc
(h)
(%)
75
78
70
65
71
60
69
75
69
64
63
58
56
68
1
2
1
1
1
1
1
1
1
1
1
1
1
1
6
7
Ph
3a
3a
3a
3a
3a
3a
3b
3b
3b
3b
3b
3b
3a
3a
5a
5b
5c
5d
5e
5f
5g
5h
5i
8
1
stretching in its IR spectrum at 1741 cm–1, and in its H
4-i-PrC6H4
4-F3COC6H4
2-MeC6H4
4-FC6H4
2,6-Me2C6H3
Ph
6
NMR spectrum the appearance of acetyl protons as a sin-
glet at d = 2.31 ppm.
3
8
4
12
8
Table 1 Effect of Various Catalysts, and Solvents in the Condensa-
tion of D-Glucose and Acetylation To Give 5aa
5
Entry Catalyst (10 mol%) Solvent
Temp Time Yieldb
6
12
8
(°C)
80
80
80
80
85
85
90
90
80
80
80
80
80
80
80
80
(h)
(%)
7
1
2
TBAB
H2O
6
39
8
4-i-PrC6H4
4-F3COC6H4
2-MeC6H4
4-FC6H4
2,6-Me2C6H3
Ph
6
TBAB
EtOH
8
71
9
8
3
TBAB
neat
8
75
10
11
12
13
14
5j
5k
5l
12
8
4
TBAB
EtOH–H2O
H2O
8
65
5
TBAI
12
12
12
12
12
24
24
24
6
40
12
8
6
TBAI
EtOH
37
8
7
TBAI
neat
30
Ph
9
6
8
TBAI
EtOH–H2O
H2O
35
a See Schemes 1 and 2.
b Products were characterized by IR, 1H and 13C NMR, and MS.
c Yields refer to pure products after chromatography.
9
TBAF
37
10
11
12
13
14
15
16
TBAF
EtOH
trace
trace
trace
37
TBAF
neat
Also we have examined the generality of the reaction by
reacting sugars such as xylose (6) and mannose (7) with
aniline and acetylacetone (3a) in the presence of tetrabu-
tylammonium bromide (10 mol%). The reaction proceed-
ed under solvent-free conditions at 80 °C to give the
corresponding products 8 and 9 in 56% and 68% yield, re-
spectively (Scheme 2).
TBAF
EtOH–H2O
H2O
SnCl2·2H2O
SnCl2·2H2O
SnCl2·2H2O
SnCl2·2H2O
EtOH
8
43
neat
8
34
In conclusion, this paper describes a convenient and effi-
cient process for the synthesis of annulated pyrrole deriv-
atives through the coupling of various in situ generated
enamines (derived from arylamines and 1,3-ketones) with
aldose sugars in the presence of 10 mol% of TBAB under
solvent free-conditions at 80 °C. This methodology offers
very attractive features, such as a simple experimental
procedure, reduced reaction times, higher yields, and eco-
nomic viability, when compared with conventional meth-
ods as well as with other catalysts, and it will have wide
scope in organic synthesis. We believe that this procedure
is a convenient and user-friendly alternative process for
the synthesis of annulated pyrrole derivatives.
EtOH–H2O
8
30
a Conditions: D-glucose (1, 5.5 mmol), aniline (5.5 mmol), and acetyl-
acetone (3a, 6.11 mmol).
b Isolated yield of 5a.
In order to extend the scope of this catalytic transforma-
tion, the general applicability of this method was verified
by reacting various anilines 2 with D-glucose (1) and
acetylacetone (3a) or ethyl acetoacetate (3b) (Table 2). D-
Glucose (1) on reaction with 4-isopropylaniline in the
presence of tetrabutylammonium bromide at 80 °C in
acetylacetone (3a) for six hours rapidly produced the cor-
responding annulated pyrrole derivative 4b, which was
acetylated to give 5b (entry 2). The results were excellent
in terms of yields and product purity of 5a–l in the pres-
ence of tetrabutylammonium bromide and the character-
All the commercial reagents and solvents were used without further
purification unless otherwise stated. Melting points were recorded
on a Buchi 535 melting point apparatus and are uncorrected. All the
reactions were monitored by TLC (pre-coated silica gel 60F254
plates, Merck). Compounds were visualized with UV light at 254
nm and 365 nm, I2, and heating plates after dipping in 2% phospho-
molybdic acid in 15% aq H2SO4 soln. IR spectra were recorded on
1
ization of products was fully supported by IR, H NMR,
and mass spectrometry and comparison of known com-
pounds with authentic samples.4
Synthesis 2010, No. 19, 3374–3378 © Thieme Stuttgart · New York

3376
L. Nagarapu et al.
PAPER
O
PhNH2
R1
O
OH
OH
2
R1
O
+
O
O
1. TBAB, 80 °C
2. Ac2O, DMAP
HO
AcO
N
OH
Ph
6 R1 = H (xylose)
7 R1 = CH2OH (mannose)
8 R1 = H
3a
9 R1 = CH2OAc
Scheme 2
Perkin-Elmer 683 or 1310 FT-IR spectrophotometers as KBr pel-
lets. NMR spectra were recorded on Varian Unity-400 and Bruker
AMX 300 spectrometers at 400 and 300 MHz, respectively, using
TMS as an internal standard. 13C NMR was recorded on a Varian
Unity-400 at 100 MHz using CDCl3 as internal standard. Mass
spectra were recorded on a VG Micromass 7070H and a Finnigan
Mat 1020B mass spectrometers operating at 70 eV.
13C NMR (50 MHz, CDCl3): d = 194.3 (COCH3), 170.7, 169.9,
149.3, 139.6, 133.8, 127.4, 127.1, 110.9, 107.8, 75.3, 65.8, 62.2,
33.8, 30.5, 29.6, 25.5, 23.8, 21.0, 20.7, 12.7.
MS (ESI): m/z = 428 [M + 1], 450 [M + Na].
(5R,6S)-6-Acetoxy-5-(acetoxymethyl)-3-acetyl-2-methyl-1-[4-
(trifluoromethoxy)phenyl]-1,4,5,6-tetrahydropyrano[3,2-
b]pyrrole (5c)
Annulated Pyrrole Derivatives 5a–n; General Procedure
D-Glucose (1; 1.0 g, 5.5 mmol), aniline 2 (6.11 mmol, 1.1 equiv),
2,4-dione 3 (6.11 mmol, 1.l equiv), and TBAB (10 mol%) were
stirred at 80 °C for 8 h (see Table 2). When the reaction was com-
plete (TLC), the mixture was extracted with CHCl3 (2 × 15 mL).
The combined organic extracts were washed with H2O and dried
(anhyd Na2SO4). Removal of solvent followed by purification by
column chromatography (silica gel, EtOAc–n-hexane, 4:6) afforded
pure dihydroxy product, which was acetylated using Ac2O (7.3
mmol), pyridine (7.3 mmol), and DMAP (catalytic amount) in
CH2Cl2 (5 mL). The reaction mixture was stirred at r.t. for 30 min,
then poured into ice-water (50 mL) and extracted with CH2Cl2 (2 ×
25 mL). The combined organic layer was washed with H2O (2 × 25
mL), dried (anhyd Na2SO4) and evaporated to yield pure acetylated
products in 55–78% yields.
Brown syrupy solid; yield: 1.82 g (70%).
IR: 2924, 2854, 1744, 1652, 1610, 1506, 1373, 1256, 1168, 1045,
852, 765, 605 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.06 (s, 3 H, OAc), 2.09 (s, 3 H,
OAc), 2.31 (s, 3 H, CH3), 2.43 (s, 3 H, COCH3), 2.43 (dd, J = 6.98,
9.42 Hz, 1 H, Ha2), 2.78 (dd, J = 6.22, 9.52 Hz, 1 H, Ha1), 4.26–4.31
(m, 2 H, Hd2, Hc), 4.44 (q, J = 6.59, 6.95 Hz, 1 H, Hd1), 5.15 (q,
J = 6.59 Hz, 1 H, Hb), 7.24 (d, J = 8.79 Hz, 2 H, Ar), 7.34 (d,
J = 8.42 Hz, 2 H, Ar).
MS (ESI): m/z = 470 [M + 1], 492 [M + Na].
(5R,6S)-6-Acetoxy-5-(acetoxymethyl)-3-acetyl-2-methyl-1-(2-
methylphenyl)-1,4,5,6-tetrahydropyrano[3,2-b]pyrrole (5d)
Brown syrupy solid; yield: 1.45 g (65%).
IR: 2926, 2857, 1744, 1652, 1607, 1497, 1457, 1401, 1371, 1234,
1144, 1044, 972, 853, 759, 664, 605 cm–1.
(5R,6S)-6-Acetoxy-5-(acetoxymethyl)-3-acetyl-2-methyl-1-phe-
nyl-1,4,5,6-tetrahydropyrano[3,2-b]pyrrole (5a)
Brown syrupy solid; yield: 1.60 g (75%).
1H NMR (300 MHz, CDCl3): d = 2.00 (s, 3 H, CH3), 2.04 (s, 3 H,
CH3), 2.10 (s, 3 H, OAc), 2.19 (s, 3 H, OAc), 2.44 (s, 3 H, COCH3),
2.28–2.40 (m, 1 H, Ha2), 2.52–2.76 (m, 1 H, Ha1), 4.22–4.31 (m, 2
H, Hd2, Hc), 4.43 (q, J = 5.28 Hz, 1 H, Hd1), 5.16 (q, J = 6.42 Hz, 1
H, Hb), 7.10 (d, J = 7.55 Hz, 1 H, Ar), 7.24–7.36 (m, 3 H).
13C NMR (75 MHz, CDCl3): d = 194.3, 170.6, 169.8, 139.5, 136.2,
135.0, 133.6, 131.0, 129.2, 128.1, 126.9, 110.7, 107.5, 75.4, 65.7,
62.0, 30.4, 29.5, 25.1, 20.9, 17.0, 12.2.
IR: 2927, 1741, 1646, 1604, 1497, 1372, 1232, 1142, 1042, 970,
758, 701, 605 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.05 (s, 3 H, OAc), 2.09 (s, 3 H,
OAc), 2.31 (s, 3 H, CH3), 2.44 (s, 3 H, COCH3), 2.42 (dd, J = 6.79,
9.42 Hz, 1 H, Ha2), 2.78 (dd, J = 6.04, 9.44 Hz, 1 H, Ha1), 4.28 (m,
2 H, Hd2, Hc), 4.43 (dd, J = 6.42, 6.04 Hz, 1 H, Hd1), 5.15 (q,
J = 6.79 Hz, 1 H, Hb), 7.18 (d, J = 6.79 Hz, 2 H, Ar), 7.38–7.51 (m,
3 H, Ar).
13C NMR (75 MHz, CDCl3): d = 194.4 (COCH3), 170.6, 169.9,
136.0, 133.7, 129.4, 128.5, 127.4, 111.0, 107.8, 75.3, 65.7, 62.2,
30.5, 25.4, 20.9, 12.7.
MS (ESI): m/z = 400 [M + 1], 422 [M + Na].
(5R,6S)-6-Acetoxy-5-(acetoxymethyl)-3-acetyl-1-(4-fluorophe-
nyl)-2-methyl-1,4,5,6-tetrahydropyrano[3,2-b]pyrrole (5e)
Brown syrupy solid; yield: 1.59 g (71%).
MS (ESI): m/z = 385 [M + 1], 408 [M + Na].
IR: 2928, 2857, 1744, 1652, 1609, 1507, 1373, 1227, 1146, 1044,
971, 844, 757, 664, 605 cm–1.
(5R,6S)-6-Acetoxy-5-(acetoxymethyl)-3-acetyl-1-(4-isopropyl-
phenyl)-2-methyl-1,4,5,6-tetrahydropyrano[3,2-b]pyrrole (5b)
Brown syrupy solid; yield: 1.86 g (78%).
1H NMR (300 MHz, CDCl3): d = 2.06 (s, 3 H, OAc), 2.09 (s, 3 H,
OAc), 2.30 (s, 3 H, CH3), 2.43 (s, 3 H, COCH3), 2.36 (dd, J = 6.79,
8.87 Hz, 1 H, Ha2), 2.76 (dd, J = 6.04, 9.44 Hz, 1 H, Ha1), 4.24–4.30
(m, 2 H, Hd2, Hc), 4.43 (q, J = 6.42 Hz, 1 H, Hd1), 5.13 (q, J = 6.61
Hz, 1 H, Hb), 7.17 (d, J = 6.42 Hz, 4 H, Ar).
13C NMR (75 MHz, CDCl3): d = 194.4, 170.6, 169.9, 163.9, 139.8,
133.8, 129.3, 116.7, 116.4, 111.2, 107.9, 75.4, 65.7, 62.1, 30.6,
29.6, 25.4, 20.9, 12.6.
IR: 2961, 2926, 1744, 1649, 1607, 1503, 1372, 1233, 1142, 1048,
965, 840, 756, 603 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.25 [m, 1 H, CH(CH3)2], 1.29 (s,
3 H, CH3), 1.31 (s, 3 H, CH3), 2.05 (s, 3 H, OAc), 2.09 (s, 3 H, OAc),
2.3 (s, 3 H, CH3), 2.44 (s, 3 H, COCH3), 2.78 (dd, J = 6.79, 9.42 Hz,
1 H, Ha2), 2.97 (dd, J = 6.04, 9.63 Hz, 1 H, Ha1), 4.24–4.30 (m, 2 H,
Hd2, Hc), 4.44 (dd, J = 6.61, 6.04 Hz, 1 H, Hd1), 5.15 (q, J = 6.79 Hz,
1 H, Hb), 7.08 (d, J = 7.93 Hz, 2 H, Ar), 7.30 (d, J = 8.30 Hz, 2 H,
Ar).
MS (ESI): m/z = 404 [M + 1], 426 [M + Na].
Synthesis 2010, No. 19, 3374–3378 © Thieme Stuttgart · New York

PAPER
Synthesis of Annulated Pyrroles
3377
(5R,6S)-6-Acetoxy-5-(acetoxymethyl)-3-acetyl-1-(2,6-dimeth-
ylphenyl)-2-methyl-1,4,5,6-tetrahydropyrano[3,2-b]pyrrole (5f)
Brown syrupy solid; yield: 1.38 g (60%).
2.17 (s, 3 H, CH3), 2.33 (dd, J = 7.02, 8.68 Hz, 1 H, Ha2), 2.55 (dd,
J = 6.04, 9.25 Hz, 1 H, Ha1), 4.21–4.32 (m, 4 H, Hd2, Hc, CH2CH3),
4.45 (q, J = 6.70 Hz, 1 H, Hd1), 5.16 (q, J = 6.70 Hz, 1 H, Hb), 7.12
(d, J = 7.34 Hz, 1 H, Ar), 7.25–7.36 (d, J = 8.30 Hz, 3 H, Ar).
IR: 2924, 2856, 1744, 1607, 1497, 1372, 1234, 1140, 1041, 969,
774, 652, 605 cm–1.
MS (ESI): m/z = 430 [M + 1], 452 [M + Na].
1H NMR (300 MHz, CDCl3): d = 1.95 (s, 6 H, CH3), 2.04 (s, 3 H,
CH3), 2.10 (s, 3 H, OAc), 2.15 (s, 3 H, OAc), 2.44 (s, 3 H, COCH3),
2.18–2.42 (m, 1 H, Ha2), 2.52–2.66 (m, 1 H, Ha1), 4.23–4.32 (m, 2
H, Hd2, Hc), 4.43 (q, J = 6.23 Hz, 1 H, Hd1), 5.16 (q, J = 6.61 Hz, 1
H, Hb), 7.16 (m, 3 H, Ar).
Ethyl (5R,6S)-6-Acetoxy-5-(acetoxymethyl)-2-methyl-1-(4-fluo-
rophenyl)-1,4,5,6-tetrahydropyrano[3,2-b]pyrrole-3-carboxy-
late (5k)
Brown syrupy solid; yield: 1.51 g (63%).
IR: 2925, 2854, 1743, 1694, 1614, 1511, 1373, 1226, 1145, 1047,
844, 764, 604 cm–1.
MS (ESI): m/z = 414 [M + 1], 436 [M + Na].
Ethyl (5R,6S)-6-Acetoxy-5-(acetoxymethyl)-2-methyl-1-phenyl-
1,4,5,6-tetrahydropyrano[3,2-b]pyrrole-3-carboxylate (5g)
Brown syrupy solid; yield: 1.68 g (69%).
1H NMR (300 MHz, CDCl3): d = 1.36 (t, J = 7.17 Hz, 3 H,
CH2CH3), 2.04 (s, 3 H, OAc), 2.09 (s, 3 H, OAc), 2.28 (s, 3 H, CH3),
2.38 (dd, J = 6.79, 8.68 Hz, 1 H, Ha2), 2.75 (dd, J = 5.85, 9.25 Hz, 1
H, Ha1), 4.22–4.33 (m, 4 H, Hd2, Hc, CH2CH3), 4.45 (q, J = 6.61 Hz,
1 H, Hd1), 5.13 (q, J = 6.61 Hz, 1 H, Hb), 7.17 (d, J = 6.04 Hz, 4 H,
Ar).
IR: 2930, 1743, 1609, 1503, 1444, 1376, 1236, 1140, 1047, 917,
764, 699, 656 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.37 (t, J = 7.17 Hz, 3 H,
CH2CH3), 2.03 (s, 3 H, OAc), 2.09 (s, 3 H, OAc), 2.30 (s, 3 H, CH3),
2.40 (dd, J = 6.42, 9.06 Hz, 1 H, Ha2), 2.75 (dd, J = 6.04, 9.44 Hz, 1
H, Ha1), 4.23–4.32 (m, 4 H, Hd2, Hc, CH2CH3), 4.45 (q, J = 6.42,
6.79 Hz, 1 H, Hd1), 5.14 (q, J = 6.79 Hz, 1 H, Hb), 7.18 (d, J = 7.17
Hz, 2 H, Ar), 7.39–7.49 (m, 3 H, Ar).
MS (ESI): m/z = 434 [M + 1], 456 [M + Na].
Ethyl (5R,6S)-6-Acetoxy-5-(acetoxymethyl)-1-(2,6-dimethyl-
phenyl)-2-methyl-1,4,5,6-tetrahydropyrano[3,2-b]pyrrole-3-
carboxylate (5l)
Brown syrupy solid; yield: 1.43 g (58%).
MS (ESI): m/z = 416 [M + 1], 438 [M + Na].
IR: 2926, 2856, 1748, 1700, 1604, 1531, 1445, 1371, 1221, 1131,
1099, 1046, 952, 777, 665 cm–1.
Ethyl (5R,6S)-6-Acetoxy-5-(acetoxymethyl)-1-(4-isopropylphe-
nyl)-2-methyl-1,4,5,6-tetrahydropyrano[3,2-b]pyrrole-3-car-
boxylate (5h)
1H NMR (300 MHz, CDCl3): d = 1.34 (t, J = 7.17 Hz, 3 H,
CH2CH3), 1.92 (s, 3 H, CH3), 1.96 (d, 3 H, CH3), 1.98 (s, 3 H, CH3),
2.03 (s, 3 H, OAc), 2.14 (s, 3 H, OAc), 2.23 (dd, J = 11.70, 3.77 Hz,
1 H, Ha2), 2.52 (dd, J = 5.66, 9.82 Hz, 1 H, Ha1), 3.88 (dd, 2 H, Hd2,
Hc), 4.23 (q, 2 H, CH2CH3), 4.79 (m, 1 H, Hd1), 4.92 (q, J = 5.4 Hz,
1 H, Hb), 7.14–7.32 (m, 3 H, Ar).
Brown syrupy solid; yield: 1.90 g (75%).
IR: 2961, 2927, 1742, 1692, 1613, 1515, 1373, 1230, 1142, 1050,
838, 769, 604 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.25 [m, 1 H, CH(CH3)2], 1.29 (s,
3 H, CH3), 1.31 (s, 3 H, CH3), 1.35 (t, J = 7.17 Hz, 3 H, CH2CH3),
2.03 (s, 3 H, OAc), 2.08 (s, 3 H, OAc), 2.30 (s, 3 H, CH3), 2.76 (dd,
J = 6.42, 8.87 Hz, 1 H, Ha2), 2.96 (dd, J = 6.04, 9.44 Hz, 1 H, Ha1),
4.23–4.32 (m, 4 H, Hd2, Hc, CH2CH3), 4.46 (q, J = 6.61 Hz, 1 H,
Hd1), 5.15 (q, J = 6.61 Hz, 1 H, Hb), 7.08 (d, J = 8.30 Hz, 2 H, Ar),
7.29 (d, J = 8.12 Hz, 2 H, Ar).
MS (ESI): m/z = 444 [M + 1], 466 [M + Na].
(6S)-3-Acetyl-6-acetoxy-2-methyl-1-phenyl-1,4,5,6-tetrahydro-
pyrano[3,2-b]pyrrole (8)
Brown syrupy solid; yield: 0.96 g (56%).
IR: 2924, 1737, 1649, 1603, 1497, 1404, 1238, 1141, 1099, 1055,
963, 835, 759, 701, 664, 606 cm–1.
MS (ESI): m/z = 457 [M + 1], 480 [M + Na].
1H NMR (300 MHz, CDCl3): d = 2.07 (s, 3 H, OAc), 2.31 (s, 3 H,
CH3), 2.45 (s, 3 H, COCH3), 2.38 (dd, J = 12.46, 3.77 Hz, 1 H, Ha2),
2.80 (dd, J = 10.57, 5.47 Hz, 1 H, Ha1), 4.06 (d, J = 11.89 Hz, 1 H,
Hc2), 4.21 (d, J = 5.66, 4.91 Hz, 1 H, Hc1), 5.18 (q, J = 5.09 Hz, 1 H,
Hb), 7.19 (d, J = 6.79 Hz, 2 H, Ar), 7.40–7.50 (m, 3 H, Ar).
Ethyl (5R,6S)-6-Acetoxy-5-(acetoxymethyl)-2-methyl-1-[4-(tri-
fluoromethoxy)phenyl]-1,4,5,6-tetrahydropyrano[3,2-b]pyr-
role-3-carboxylate (5i)
Brown syrupy solid; yield: 1.93 g (69%).
IR: 2925, 2855, 1745, 1697, 1613, 1511, 1373, 1257, 1166, 1046,
852, 768, 669, 605 cm–1.
13C NMR (75 MHz, CDCl3): d = 194.6, 170.2, 140.6, 135.7, 133.0,
129.1, 128.2, 127.1, 119.5, 108.1, 67.4, 65.1, 30.1, 25.6, 20.8, 12.4.
1H NMR (300 MHz, CDCl3): d = 1.36 (t, J = 7.02 Hz, 3 H,
CH2CH3), 2.04 (s, 3 H, OAc), 2.09 (s, 3 H, OAc), 2.31 (s, 3 H, CH3),
2.40 (dd, J = 6.79, 8.68 Hz, 1 H, Ha2), 2.77 (dd, J = 6.04, 9.44 Hz, 1
H, Ha1), 4.22–4.32 (m, 4 H, Hd2, Hc, CH2CH3), 4.45 (q, J = 6.79 Hz,
1 H, Hd1), 5.14 (q, J = 6.79 Hz, 1 H, Hb), 7.29 (d, J = 9.06 Hz, 2 H,
Ar), 7.33 (d, J = 8.68 Hz, 2 H, Ar).
MS (ESI): m/z = 314 [M + 1], 336 [M + Na].
(5R,6S)-6-Acetoxy-5-(acetoxymethyl)-3-acetyl-2-methyl-1-phe-
nyl-1,4,5,6-tetrahydropyrano[3,2-b]pyrrole (9)
Brown syrupy solid; yield: 1.45 g (68%).
IR: 2924, 2854, 1742, 1650, 1606, 1498, 1399, 1233, 1141, 1042,
971, 764, 702, 664 cm–1.
MS (ESI): 500 [M + 1], 522 [M + Na].
1H NMR (300 MHz, CDCl3): d = 2.06 (s, 3 H, OAc), 2.09 (s, 3 H,
OAc), 2.32 (s, 3 H, CH3), 2.44 (s, 3 H, COCH3), 2.42 (dd, J = 6.79,
9.42 Hz, 1 H, Ha2), 2.78 (dd, J = 6.04, 9.44 Hz, 1 H, Ha1), 4.24–4.31
(m, 2 H, Hd2, Hc), 4.44 (dd, J = 6.42, 6.04 Hz, 1 H, Hd1), 5.15 (q,
J = 6.79 Hz, 1 H, Hb), 7.18 (d, J = 6.79 Hz, 2 H, Ar), 7.40–7.51 (m,
3 H, Ar).
Ethyl (5R,6S)-6-Acetoxy-5-(acetoxymethyl)-2-methyl-1-(2-
methylphenyl)-1,4,5,6-tetrahydropyrano[3,2-b]pyrrole-3-car-
boxylate (5j)
Brown syrupy solid; yield: 1.54 g (64%).
IR: 2925, 2854, 1743, 1694, 1498, 1450, 1373, 1231, 1147, 1118,
1045, 764, 607 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.37 (t, J = 7.02 Hz, 3 H,
CH2CH3), 1.99 (s, 3 H, CH3), 2.02 (d, 3 H, CH3), 2.08 (s, 3 H, OAc),
MS (ESI): m/z = 386 [M + 1], 408 [M + Na].
Synthesis 2010, No. 19, 3374–3378 © Thieme Stuttgart · New York

3378
L. Nagarapu et al.
PAPER
(4) (a) Smietana, M.; Mioskowski, C. Org. Lett. 2001, 3, 1037.
(b) Amantini, C.; Fringuelli, F.; Pizzo, F.; Vaccaro, L.
J. Org. Chem. 2001, 66, 6734. (c) Selvakumar, K.; Zapt, A.;
Beller, M. Org. Lett. 2002, 4, 3031.
(5) Ranu, B. C.; Dey, S. S.; Hajra, A. Tetrahedron 2003, 59,
2417.
Acknowledgment
The authors are thankful to Dr. J. S. Yadav, Director IICT–Hydera-
bad and Dr. V. V. Narayana Reddy, Head, Organic Chemistry Divi-
sion-II, IICT for their constant encouragement and support. V.N.C.
and S.K. thank CSIR, New Delhi for the award of fellowships.
(6) Ranu, B. C.; Das, A.; Samanta, S. J. Chem. Soc., Perkin
Trans. 1 2002, 1520.
(7) Kantevari, S.; Chary, M. V.; Das, A. P. R.; Srinivas, V. N.
V.; Lingaiah, N. Catal. Commun. 2008, 9, 2013.
(8) Amantini, D.; Fringuelli, F.; Pizzo, F.; Vaccaro, L. J. Org.
Chem. 2001, 66, 6734.
(9) Kantevari, S.; Chary, M. V.; Das, A. P. R.; Srinivas, V. N.
V.; Lingaiah, N. Catal. Commun. 2008, 9, 1575.
(10) (a) Nagarapu, L.; Chary, M. V.; Supriya, B.; Satyender, A.;
Rajashaker, B. Synthesis 2009, 2279. (b) Nagarapu, L.;
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Synthesis 2010, No. 19, 3374–3378 © Thieme Stuttgart · New York