The first mineral-catalyzed one-pot [3+1+2] coupling protocol for multifunctionalized fused-ring pyrimidines

Article abstract of DOI:10.1055/s-0029-1216874

This is the first report on montmorillonite K-10 clay(nanoclay)-catalyzed, domino reactions of unprotected D-glucose/D-xylose with amidines/guanidine and an activated natural amino acid 2-phenyl-1,3-oxazol-5-one. The procedure results in an efficient annu

Full text of DOI:10.1055/s-0029-1216874

2802
PAPER
The First Mineral-Catalyzed One-Pot [3+1+2] Coupling Protocol for
Multifunctionalized Fused-Ring Pyrimidines
S
ynthesis of Mu
a
ltifunction
l
alized
Fused-
D
Ring Pyrimidines har S. Yadav,* Ankita Rai
Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211002, India
Fax +91(532)2460533; E-mail: ldsyadav@hotmail.com
Received 14 April 2009; revised 21 April 2009
NH2
H
N
H
N
Abstract: This is the first report on montmorillonite K-10 clay
HO
(nanoclay)-catalyzed, domino reactions of unprotected D-glucose/
D-xylose with amidines/guanidine and an activated natural amino
acid 2-phenyl-1,3-oxazol-5-one. The procedure results in an effi-
cient annulation of the iminosugar moiety with functionalized
pyrimidines in excellent yields (79–92%) with high trans-diaste-
reoselectivity (>94%). The reaction is effected under solvent-free
microwave irradiation conditions via amidine/guanidine-driven
coupling and ring-transformation reactions in a one-pot procedure.
N
N
CO2H
NH2
HO
OH
HO
OH
OH
OH
deoxynojirimycin
isofagomine
L-lathyrine
Figure 1 Synthetic and naturally occurring iminosugars and pyri-
midines
Key words: carbohydrates, mineral-catalyzed, amidines/guani-
dine, microwaves, ring transformation, pyrimidines
Although a number of pyrimidine syntheses have been
known for a long time, the development of more efficient
alternative strategies is of considerable relevance. In most
of the cases, construction of the pyrimidine ring is based
on the bis-nucleophile plus bis-electrophile methods14 or
on cross-coupling reactions15 and is restricted to methods
involving Pinner synthesis via 3,4- and 1,6- (I);14 1,2- and
2,3- (II);16 1,2- and 3,4- (III);17 4,5- and 1,6- (IV);18 2,3-
and 4,5- (V);19 3,4- and 4,5- (VI)20 bond-forming original
reactions (Scheme 1). Recently, we have disclosed a syn-
thesis of pyrimidine via novel 1,2- and 1,6- bond-forming
reactions (VII, Scheme 1).21 In light of this scenario, it ap-
peared interesting to annulate the pharmaceutically im-
portant iminosugars with a pyrimidine system. This
would not only afford an attractive scaffold for exploiting
chemical diversity but the presence of free polyhydroxy
groups would also render the target molecules water-
soluble and biodegradable.
Iminosugars are arousing great interest as potential thera-
peutic agents against HIV infection,1 cancer,2 diabetes,3
and other genetic and metabolic disorders4 due to their
powerful interference with glycosydases as well as gly-
cotransferases. Particularly, iminosugars are of great in-
terest as inhibitors of carbohydrate possessing enzymes.5
For example, inhibitory activities have been reported for
many naturally occurring iminosugars (deoxynojirimycin,
isofagomine;6 Figure 1), whereas migitol,7 a synthetic
glucose-mimic piperidine, is commercially available in
several countries for the treatment of diabetes. This inter-
est has generated a multitude of publications on the syn-
thesis of new iminosugars.5
The pyrimidine moiety is one of the most widespread het-
erocycles in naturally occurring compounds, such as
nucleic acids and vitamin B1,8 and is an important constit-
uent of numerous drug molecules in many therapeutic ar-
eas. Furthermore, functionalized pyrimidines9 play an
important role as analgesic,9b antihypertensive,9c anti-
pyretic,9d and anti-inflammatory drugs,9e as well as in pes-
ticides,9f herbicides,9g and as plant growth regulators.9h
For example, L-lathyrine (Figure 1), a naturally occurring
pyrimidine, shows a wide range of biological activity,
such as pollen growth inhibition, antitumor, and hypogly-
cemic activity.10 Owing to their strong deactivation to-
wards electrophilic substitution and greater reactivity in
nucleophilic additions and substitutions,11 pyrimidines
may become increasingly important as interesting struc-
tural coordinating substituted ligands for pyridyl units in
supramolecular metallo-grid-like architectures12 and in
novel inorganic/organic hybrid type molecular wires.13
N
C
C
N
C
N
C
I
N
4
C
C
II
N
N
III
C
N
C
C
C
N
5
6
N
3
N
VIII
IV
C
2
N
N
1
this work
C
N
C
V
VII
C
N
VI
N
C
C
C
C
N
N
N
Scheme 1
Herein, we report a conceptually new route for the synthe-
sis of multifunctionalized pyrimidines via 4 and 5 through
3,4-, 4,5- and 1,6 bond-forming reactions (VIII,
Scheme 1). The strategy involves using a [3+1+2] cou-
SYNTHESIS 2009, No. 16, pp 2802–2808
x
x.
x
x
.
2
0
0
9
Advanced online publication: 26.06.2009
DOI: 10.1055/s-0029-1216874; Art ID: Z07109SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of Multifunctionalized Fused-Ring Pyrimidines
2803
H
OH
H
H2N
OH
H
N
PhCOHN
O
H
N
OH
OH
OH
OH
O
H3O+
n = 3
N
N
CHO
NH
R
MW
N
R
H
6
4
O
(CHOH)n
OH
H
OH
H2N
R
NH2
K-10 clay
O
H
PhCOHN
O
H
Ph
H3O+
OH
CH2OH
OH
O
2
3
n = 4
1
N
N
N
N
OH
OH
D-xylose; n = 3
D-glucose; n = 4
R
7
R
OH
5
OH
Scheme 2 Synthesis of fused-ring pyrimidines 4–7
pling protocol starting from unprotected aldoses 1, cation. On debenzoylation, compounds 4 and 5 afforded 6
amidines/guanidine 2 and the activated natural amino acid and 7, respectively, in quantitative yields (Scheme 2).
3, followed by cyclodehydration in a one-pot procedure
Table 1 Optimization of Reaction Conditions for Compound 4a
(R = Me)
(Scheme 2 and Scheme 3). The present, unprecedented
synthesis of functionalized pyrimidines is an outcome of
our quest for novel solvent-free heterocyclization strate-
Entry Catalyst system
MW
Oil bath
gies,22 especially using carbohydrates as raw materials.23
Furthermore, the present synthetic protocol is in accord
with ‘renewable resources’ – a new and rapidly develop-
ing concept in environmental and chemical sciences that
concerns the wide use of bio-renewable materials for in-
dustry.24
Time
Yield
(%)b
Time (h)a Yield
(%)b
(min)a
1
2
3
4
5
6
K-10 clay
10
13
89
54
61
29
16
19
8
59
31
29
18
10
11
CeCl3·7H2O
8
CeCl3·7H2O/NaI 12
9
In our initial experiments, we optimized the catalyst for
the present reaction. We examined various mineral cata-
lysts for the formation of 4a (R = Me). Among the cata-
lysts tested, K-10 clay gave the best result (Table 1, entry
1). Using a CeCl3·7H2O/NaI-system and CeCl3·7H2O af-
forded the product 4a in moderate to good yields, while
poor yields of product 4a were obtained using silica gel
and neutral or acidic alumina (Table 1). Moreover, the re-
action did not take place when basic alumina was used as
the catalyst. It was also observed that significantly lower
yields of 4a were obtained using oil bath heating rather
than the microwave (MW)-activated method with all the
catalyst systems (Table 1).
silica gel
14
16
16
10
9
neutral alumina
acidic alumina
9
a Time for completion of the reaction at 85 °C as indicated by TLC.
b Yield of isolated and purified product 4a.
The chiral carbons of the precursor carbohydrates retain
their configuration in the product if they are not involved
in any bond breaking or bond formation. This fact is sup-
ported by the observation that there was no change in the
absolute configuration of any chiral carbon of D-xylose or
D-glucose when an intimate solvent-free mixture of D-xy-
lose or D-glucose (2.0 mmol) and K-10 clay (0.20 g) was
subjected to MW irradiation at 85 °C for 15 minutes, that
is, under the present reaction conditions.
The present optimized synthesis was accomplished using
MW irradiation of an equimolar intimate solvent-free
mixture of D-xylose/D-glucose 1, amidines/guanidine 2,
and 2-phenyl-1,3-oxazol-5-one (3) with K-10 clay (parti-
cle size: 32.7 nm), at 85 °C for 10–12 minutes in a Chem-
ical Laboratory Microwave Oven (Scheme 2).
The formation of 4 and 5 may be tentatively rationalized
by intramolecular attack of the nitrogen atom of the ami-
dine/guanidine moiety at the carbonyl carbon (C-5) of the
oxazol-5-one nucleus in 9 to yield the target compounds 4
and 5 (Scheme 3). This conclusion is based on the obser-
vation that the representative intermediates 9a (R = Me;
n = 3) and 9g (R = Me; n = 4) could be isolated in 45–
52% yield and that these could be converted into the cor-
responding annulated products 4a and 5a quantitatively.
Isolation and purification by recrystallization from etha-
nol afforded multifunctionalized pyrimidine analogues 4
and 5 in 79–92% yields with >94% diastereoselectivity
(Table 2) in favor of the trans-isomer as determined by 1H
NMR spectroscopy. For the trans-isomers 4 and 5, all the
OH and CH2OH groups are equatorial as shown by JH,H
values. Protons 4-H and 4a-H are axial as indicated by
their coupling constants (J4,4a = 9.6 Hz, Jtrans and
J4a,5 = 9.5 Hz, Jtrans). The diastereomeric ratios in the
crude isolates were checked by 1H NMR to note any inad-
vertent alteration of these ratios during subsequent purifi-
In summary, we have developed an unprecedented three-
component [3+2+1] coupling protocol for an expeditious
synthesis of pharmaceutically relevant multifunctional-
ized fused pyrimidines using unprotected aldoses as a bio-
Synthesis 2009, No. 16, 2802–2808 © Thieme Stuttgart · New York

2804
L. D. S. Yadav, A. Rai
PAPER
Table 2 Microwave-Activated Synthesis of 4, 5 and 9
N
H
CH2OH
O
O
C
Ph
Time (min)a Yield (%)b,c trans/cis
O
Entry Product
R
3
NH
MW
(CHOH)n
ratiod
+
(CHOH)n
CH2OH
K-10
clay
R
NH2
N
1
2
4a
4b
4c
4d
4e
4f
Me
NH2
H
10
10
12
10
89
79
88
92
90
83
86
89
91
89
82
90
45
52
98:2
95:5
97:3
96:4
96:4
98:2
96:4
95:5
97:3
95:5
98:2
96:4
95:5
95:5
2
n = 3,4
R
NH
1
8
3
CH2OH
H
R
PhCOHN
O
CH2OH
4
Ph
H
(CHOH)n
(CHOH)n
H
5
4-O2NC6H4 11
4-H2NC6H4 10
NH
H
R
NH
N
N
6
:
NH
O
Ph
O
7
5a
5b
5c
5d
5e
5f
Me
NH2
H
11
12
10
12
10 n = 3,4
9
8
H
OH
H
OH
OH
PhCOHN
O
H
PhCOHN
O
H
OH
OH
9
OH
OH
4
5
4a
3
6
7
N2
N
10
11
12
13
14
Ph
1
8
– H2O
N
NH
9
4-O2NC6H4 10
4-H2NC6H4 10
R
R
10, n = 3
4
9a
9g
Me
Me
4
6
H
OH
H
OH
PhCOHN
PhCOHN
O
H
H
OH
OH
OH
O
5
4
1
3
4a
6
N2
N
9
7
8
a Microwave irradiation time at 85 °C.
b Yield of isolated and purified products.
N
NH
HO
OH
– H2O
1'
R
R
OH
c All compounds gave C, H and N analyses within 0.34% and satis-
factory spectral data (IR, 1H NMR, 13C NMR and FAB MS).
d As determined by 1H NMR of the crude products.
OH
5
10, n = 4
Scheme 3 Plausible mechanism for the formation of fused-ring py-
rimidines 4 and 5
renewable aldehyde component, an active methylene
building block 2-phenyl-1,3-oxazol-5-one (3), and
EtOH to afford a diastereomeric mixture (>94:<6); in the crude
amidines/guanidine. The reaction is nanoclay-catalyzed products the ratio was >91:<9, as determined by 1H NMR spectros-
copy. A second recrystallization from EtOH furnished an analyti-
and effected under solvent-free MW irradiation condi-
tions in a one-pot procedure.
cally pure sample of a single diastereomer 4 or 5 (Table 1). On the
basis of comparison of J values to those in the literature,26–32 the
trans-stereochemistry was assigned to 4 and 5, as the coupling con-
Melting points were determined by an open glass capillary method
and are uncorrected. IR spectra in KBr were recorded on a Perkin–
Elmer 993 IR spectrophotometer. H NMR spectra were recorded
stant of the major trans-isomer (J4,4a = 9.6 Hz) was higher than for
those of the minor cis-diastereomer (J4,4a = 4.8 Hz).
1
on a Bruker WM-40 C (400 MHz) FT spectrometer in DMSO-d6 us-
ing TMS as internal reference. 13C NMR spectra were recorded on
the same instrument at 100 MHz in DMSO-d6 and TMS was used
as internal reference. Mass (EI) spectra were recorded on a JEOL D-
300 mass spectrometer. Elemental analyses were carried out in a
Coleman automatic carbon, hydrogen and nitrogen analyzer. A
Chemical Laboratory Microwave Oven (Model; BP-310/50, 230 V,
50 Hz power input) was used for all experiments. All chemicals
used were reagent grade and were used as received without further
purification. Silica gel-G was used for TLC.
N-(4,4a,5,6,7,8-Hexahydro-5,6,7-trihydroxy-1-methyl-3-oxo-
3H-pyrido[1,2-f]pyrimidin-4-yl)benzamide (4a)
Pale-yellow powder; mp 119–121 °C.
IR (KBr): 3342, 3315, 3007, 2955, 2890, 1684, 1680, 1675, 1603,
1580, 1456, 739, 695 cm–1.
1H NMR (400 MHz, DMSO-d6 + D2O): d = 1.1 (s, 3 H, Me), 2.67
(dd, J8ax,eq = 12.9 Hz, J7,8ax = 9.8 Hz, 1 H, H-8ax), 3.31 (ddd,
J7,6 = 9.1 Hz, J8ax,7 = 9.8 Hz, J7,8eq = 3.5 Hz, 1 H, H-7), 3.73 (dd,
J6,7 = 9.1 Hz, J5,6 = 8.9 Hz, 1 H, H-6), 3.92 (dd, J8ax,eq = 12.9 Hz,
J7,8eq = 3.5 Hz, 1 H, H-8eq), 4.12 (dd, J5,6 = 8.9 Hz, J4a,5 = 9.5 Hz,
1 H, H-5), 5.05 (dd, J4,4a = 9.6 Hz, J4a,5 = 9.5 Hz, 1 H, H-4a), 6.17
(d, J4,4a = 9.6 Hz, 1 H, H-4), 7.20–7.79 (m, 5 H, ArH).
13C NMR (DMSO-d6): d = 23.5, 41.0, 43.9, 54.7, 70.3, 71.4, 75.5,
126.9, 128.7, 132.6, 134.5, 163.9, 167.8, 201.
MS (FAB): m/z = 334 [MH+].
Fused-Ring Pyrimidines 4 and 5; General Procedure
An intimate, solvent-free mixture of aldose 1 (2.0 mmol), amidine/
guanidine 2 (2.0 mmol), oxazolone 3 (2.0 mmol) and Montmorillo-
nite K-10 clay (0.20 g, particle size 32.7 nm) was taken in a 20 mL
vial and subjected to MW irradiation at 85 °C for 10–12 min
(Table 2). After completion of the reaction as indicated by TLC,
H2O (10 mL) was added and the reaction mixture was stirred for 10
min. The yellowish precipitate thus obtained was washed with H2O
(2 × 5 mL) to give the crude product which was recrystallized from
Anal. Calcd for C16H19N3O5: C, 57.65; H, 5.75; N, 12.61. Found: C,
57.96; H, 5.46; N, 12.81.
Synthesis 2009, No. 16, 2802–2808 © Thieme Stuttgart · New York

PAPER
Synthesis of Multifunctionalized Fused-Ring Pyrimidines
2805
N-(1-Amino-4,4a,5,6,7,8-hexahydro-5,6,7-trihydroxy-3-oxo-
3H-pyrido[1,2-f]pyrimidin-4-yl)benzamide (4b)
Pale-yellow powder; mp 115–118 °C.
Hz, J7,8eq = 3.6 Hz, 1 H, H-7), 3.74 (dd, J6,7 = 9.0 Hz, J5,6 = 8.9 Hz,
1 H, H-6), 3.90 (dd, J8ax,eq = 12.7 Hz, J7,8eq = 3.6 Hz, 1 H, H-8eq),
4.16 (dd, J5,6 = 8.9 Hz, J4a,5 = 9.4 Hz, 1 H, H-5), 5.09 (dd, J4,4a = 9.5
Hz, J4a,5 = 9.4 Hz, 1 H, H-4a), 6.13 (d, J4,4a = 9.5 Hz, 1 H, H-4),
7.06–7.81 (m, 9 H, ArH).
13C NMR (DMSO-d6): d = 44.0, 45.1, 54.6, 63.8, 66.1, 74.7, 122.7,
126.9, 128.2, 129.3, 130.6, 136.9, 138.4, 149.9, 164.0, 200.8.
IR (KBr): 3344, 3317, 3254, 3004, 2956, 1682, 1679, 1672, 1602,
1581, 1457, 732, 693 cm–1.
1H NMR (400 MHz, DMSO-d6 + D2O): d = 2.65 (dd, J8ax,eq = 12.8
Hz, J7,8ax = 9.9 Hz, 1 H, H-8ax), 3.33 (ddd, J6,7 = 9.3 Hz, J7,8ax = 9.9
Hz, J7,8eq = 3.3 Hz, 1 H, H-7), 3.76 (dd, J6,7 = 9.3 Hz, J5,6 = 8.7 Hz,
1 H, H-6), 3.91 (dd, J8ax,eq = 12.8 Hz, J7,8eq = 3.3 Hz, 1 H, H-8eq),
4.15 (dd, J5,6 = 8.7 Hz, J4a,5 = 9.4 Hz, 1 H, H-5), 5.07 (dd, J4,4a = 9.6
Hz, J4a,5 = 9.4 Hz, 1 H, H-4a), 6.18 (d, J4,4a = 9.6 Hz, 1 H, H-4),
7.19–7.75 (m, 5 H, ArH).
MS (FAB): m/z = 441 [MH+].
Anal. Calcd for C21H20N4O7: C, 57.27; H, 4.58; N, 12.72. Found: C,
57.03; H, 4.92; N, 12.84.
N-{1-(4-Aminophenyl)-5,6,7-trihydroxy-3-oxo-4,4a,5,6,7,8-
hexahydro-3H-pyrido[1,2-c]pyrimidin-4-yl}benzamide (4f)
Pale-yellow powder; mp 117–120 °C.
13C NMR (DMSO-d6): d = 41.5, 42.7, 52.4, 63.9, 65.9, 75.3, 128.4,
129.6, 131.2, 137.9, 163.3, 164.7, 200.7.
MS (FAB): m/z = 335 [MH+].
IR (KBr): 3346, 3319, 3007, 2952, 1682, 1678, 1674, 1602, 1581,
1456, 739, 690 cm–1.
Anal. Calcd for C15H18N4O5: C, 53.89; H, 5.43; N, 16.76. Found: C,
53.64; H, 5.62; N, 16.88.
1H NMR (400 MHz, DMSO-d6 + D2O): d = 2.64 (dd, J8ax,eq = 12.8
Hz, J7,8ax = 9.9 Hz, 1 H, H-8ax), 3.35 (ddd, J6,7 = 9.4 Hz, J7,8ax = 9.6
Hz, J7,8eq = 3.8 Hz, 1 H, H-7), 3.73 (dd, J6,7 = 9.4 Hz, J5,6 = 8.7 Hz,
1 H, H-6), 3.92 (dd, J8ax,eq = 12.8 Hz, J7,8eq = 3.8 Hz, 1 H, H-8eq),
4.14 (dd, J5,6 = 8.7 Hz, J4a,5 = 9.2 Hz, 1 H, H-5), 5.07 (dd, J4,4a = 9.5
Hz, J4a,5 = 9.2 Hz, 1 H, H-4a), 6.15 (d, J4,4a = 9.5 Hz, 1 H, H-1),
7.07–7.84 (m, 9 H, ArH).
13C NMR (DMSO-d6): d = 43.9, 45.5, 54.7, 62.6, 66.9, 74.5, 114.7,
122.1, 127.3, 129.4, 130.6, 131.9, 136.6, 148.1, 163.9, 200.9.
MS (FAB): m/z = 411 [MH+].
N-(4,4a,5,6,7,8-Hexahydro-5,6,7-trihydroxy-3-oxo-3H-pyri-
do[1,2-f]pyrimidin-4-yl)benzamide (4c)
Pale-yellow powder; mp 109–112 °C.
IR (KBr): 3345, 3319, 3002, 2952, 1685, 1676, 1670, 1604, 1584,
1455, 736, 691 cm–1.
1H NMR (400 MHz, DMSO-d6 + D2O): d = 1.3 (s, 1 H, CH), 2.69
(dd, J8ax,eq = 12.6 Hz, J7,8ax = 9.8 Hz, 1 H, H-8ax), 3.34 (ddd,
J6,7 = 9.4 Hz, J7,8ax = 9.8 Hz, J7,8eq = 3.6 Hz, 1 H, H-7), 3.72 (dd,
J6,7 = 9.4 Hz, J5,6 = 8.6 Hz, 1 H, H-6), 3.94 (dd, J8ax,eq = 12.6 Hz,
J7,8eq = 3.6 Hz, 1 H, H-8eq), 4.11 (dd, J5,6 = 8.6 Hz, J4a,5 = 9.6 Hz,
1 H, H-5), 5.04 (dd, J4,4a = 9.7 Hz, J4a,5 = 9.6 Hz, 1 H, H-4a), 6.97
(d, J4,4a = 9.7 Hz, 1 H, H-4), 7.21–7.80 (m, 5 H, ArH).
Anal. Calcd for C21H22N4O5: C, 61.45; H, 5.40; N, 13.65. Found: C,
61.33; H, 5.64; N, 13.35.
N-{4,4a,5,6,7,8-Hexahydro-5,6,7-trihydroxy-8-(hydroxymeth-
yl)-1-methyl-3-oxo-3H-pyrido[1,2-f]pyrimidin-4-yl}benzamide
(5a)
13C NMR (DMSO-d6): d = 45.9, 47.2, 53.4, 62.8, 66.5, 74.9, 128.9,
130.1, 131.6, 137.7, 162.9, 164, 200.9.
Pale-yellow powder; mp 129–131 °C.
MS (FAB): m/z = 320 [MH+].
IR (KBr): 3341, 3317, 3005, 2962, 2894, 1685, 1675, 1667, 1585,
1455, 735, 692 cm–1.
Anal. Calcd for C15H17N3O5: C, 56.42; H, 5.37; N, 13.16. Found: C,
56.60; H, 5.26; N, 13.47.
1H NMR (400 MHz, DMSO-d6 + D2O): d = 1.2 (s, 3 H, Me), 3.16
(ddd, J7,8 = 9.6 Hz, J1¢a,8 = 5.9 Hz, J1¢b,8 = 2.7 Hz, 1 H, H-8), 3.31
(dd, J6,7 = 9.4 Hz, J7,8 = 9.6 Hz, 1 H, H-7), 3.53 (dd, J1¢a,1¢b = 12.3
Hz, J1¢a,8 = 5.9 Hz, 1 H, H-1¢a), 3.65 (dd, J6,7 = 9.4 Hz, J5,6 = 9.1 Hz,
1 H, H-6), 3.83 (dd, J1¢a,1¢b = 12.3 Hz, J1¢b,8 = 2.7 Hz, 1 H, H-1¢b),
4.17 (dd, J5,6 = 9.1 Hz, J4a,5 = 9.3 Hz, 1 H, H-5), 4.97 (dd, J4,4a = 9.5
Hz, J4a,5 = 9.3 Hz, 1 H, H-4a), 6.23 (d, J4,4a = 9.5 Hz, 1 H, H-4),
7.08–7.87 (m, 5 H, ArH).
13C NMR (DMSO-d6): d = 23.7, 42.1, 53.5, 54.9, 58.9, 69.2, 71.6,
74.5, 127.1, 128.8, 132.3, 134.0, 164.2, 167.5, 200.8.
MS (FAB): m/z = 363 [MH+].
N-(4,4a,5,6,7,8-Hexahydro-5,6,7-trihydroxy-3-oxo-1-phenyl-
3H-pyrido[1,2-f]pyrimidin-4-yl)benzamide (4d)
Pale-yellow powder; mp 106–108 °C.
IR (KBr): 3343, 3314, 3006, 2954, 1687, 1678, 1674, 1605, 1582,
1457, 735, 692 cm–1.
1H NMR (400 MHz, DMSO-d6 + D2O): d = 2.66 (dd, J8ax,eq = 12.9
Hz, J7,8ax = 9.7 Hz, 1 H, H-8ax), 3.32 (ddd, J6,7 = 9.2 Hz, J7,8ax = 9.7
Hz, J7,8eq = 3.5 Hz, 1 H, H-7), 3.75 (dd, J6,7 = 9.2 Hz, J5,6 = 8.8 Hz,
1 H, H-6), 3.93 (dd, J8ax,eq = 12.9 Hz, J7,8eq = 3.5 Hz, 1 H, H-8eq),
4.13 (dd, J5,6 = 8.8 Hz, J4a,5 = 9.3 Hz, 1 H, H-5), 5.03 (dd, J4,4a = 9.5
Hz, J4a,5 = 9.3 Hz, 1 H, H-4a), 6.18 (d, J4,4a = 9.5 Hz, 1 H, H-4),
7.07–7.79 (m, 10 H, ArH).
Anal. Calcd for C17H21N3O6: C, 56.19; H, 5.83; N, 11.56. Found: C,
55.98; H, 5.60; N, 11.75.
13C NMR (DMSO-d6): d = 44.6, 45.8, 53.7, 62.8, 65.9, 75.7, 124.9,
127.9, 128.8, 130.2, 131.7, 132.6, 137.4, 164.2, 201.
MS (FAB): m/z = 396 [MH+].
N-{1-Amino-4,4a,5,6,7,8-hexahydro-5,6,7-trihydroxy-8-(hy-
droxymethyl)-3-oxo-3H-pyrido[1,2-f]pyrimidin-4-yl}benz-
amide (5b)
Anal. Calcd for C21H21N3O5: C, 63.79; H, 5.35; N, 10.63. Found: C,
64.00; H, 5.64; N, 10.96.
Pale-yellow powder; mp 116–119 °C.
IR (KBr): 3343, 3314, 3259, 3007, 2961, 1687, 1674, 1669, 1587,
1456, 741, 696 cm–1.
N-{4,4a,5,6,7,8-Hexahydro-5,6,7-trihydroxy-1-(4-nitrophenyl)-
3-oxo-3H-pyrido[1,2-f]pyrimidin-4-yl}benzamide (4e)
Pale-yellow powder; mp 110–112 °C.
1H NMR (400 MHz, DMSO-d6 + D2O): d = 3.18 (ddd, J7,8 = 9.6 Hz,
J1¢a,8 = 5.7 Hz, J1¢b,8 = 2.9 Hz, 1 H, H-8), 3.34 (dd, J6,7 = 9.3 Hz,
J7,8 = 9.6 Hz, 1 H, H-7), 3.51 (dd, J1¢a,1¢b = 12.4 Hz, J1¢a,8 = 5.7 Hz,
1 H, H-1¢a), 3.63 (dd, J6,7 = 9.3 Hz, J8,9 = 9.1 Hz, 1 H, H-6), 3.84
(dd, J1¢a,1¢b = 12.4 Hz, J1¢b,8 = 2.9 Hz, 1 H, H-1¢b), 4.19 (dd, J5,6 = 9.1
Hz, J4a,5 = 9.2 Hz, 1 H, H-5), 4.95 (dd, J4,4a = 9.4 Hz, J4a,5 = 9.2 Hz,
IR (KBr): 3347, 3317, 3004, 2955, 1682, 1676, 1672, 1603, 1581,
1455, 737, 696 cm–1.
1H NMR (400 MHz, DMSO-d6 + D2O): d = 2.65 (dd, J8ax,eq = 12.7
Hz, J7,8ax = 9.7 Hz, 1 H, H-8ax), 3.34 (ddd, J6,7 = 9.0 Hz, J7,8ax = 9.7
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L. D. S. Yadav, A. Rai
PAPER
1 H, H-4a), 6.26 (d, J4,4a = 9.4 Hz, 1 H, H-4), 7.09–7.89 (m, 5 H,
13C NMR (DMSO-d6): d = 42.2, 48.4, 53.7, 60.6, 64.2, 65.8, 72.7,
ArH).
121.4, 125.6, 127.4, 128.9, 130.2, 136.7, 138.8, 149.8, 164.2, 201.
13C NMR (DMSO-d6): d = 39.4, 46.1, 53.5, 60.6, 62.9, 64.1, 72.7,
MS (FAB): m/z = 371 [MH+].
127.9, 129.1, 130.6, 136.2, 162.6, 164, 200.7.
MS (FAB): m/z = 365 [MH+].
Anal. Calcd for C22H22N4O8: C, 56.17; H, 4.71; N, 11.91. Found: C,
56.42; H, 4.42; N, 12.13.
Anal. Calcd for C16H20N4O6: C, 52.74; H, 5.53; N, 15.38. Found: C,
52.55; H, 5.84; N, 15.12.
N-{1-(4-Aminophenyl)-5,6,7-trihydroxy-8-hydroxymethyl-3-
oxo-4,4a,5,6,7,8-hexahydro-3H-pyrido[1,2-c]pyrimidin-4-
yl}benzamide (5f)
N-{4,4a,5,6,7,8-Hexahydro-5,6,7-trihydroxy-8-(hydroxymeth-
yl)-3-oxo-3H-pyrido[1,2-f]pyrimidin-4-yl}benzamide (5c)
Pale-yellow powder; mp 121–123 °C.
Pale-yellow powder; mp 124–127 °C.
IR (KBr): 3344, 3317, 3004, 2962, 1687, 1674, 1667, 1587, 1455,
737, 691 cm–1.
IR (KBr): 3347, 3319, 3004, 2964, 1684, 1672, 1669, 1586, 1459,
739, 693 cm–1.
1H NMR (400 MHz, DMSO-d6 + D2O): d = 3.17 (ddd, J7,8 = 9.8 Hz,
J1¢a,8 = 5.6 Hz, J1¢b,8 = 2.7 Hz, 1 H, H-8), 3.31 (dd, J6,7 = 9.3 Hz,
J7,8 = 9.8 Hz, 1 H, H-7), 3.54 (dd, J1¢a,1¢b = 12.3 Hz, J1¢a,8 = 5.6 Hz,
1 H, H-1¢a), 3.68 (dd, J6,7 = 9.3 Hz, J5,6 = 9.1 Hz, 1 H, H-6), 3.83
(dd, J1¢a,1¢b = 12.3 Hz, J1¢b,8 = 2.7 Hz, 1 H, H-1¢b), 4.14 (dd, J5,6 = 9.1
Hz, J4a,5 = 9.3 Hz, 1 H, H-5), 4.94 (dd, J4,4a = 9.54 Hz, J4a,5 = 9.3
Hz, 1 H, H-4a), 6.23 (d, J4,4a = 9.4 Hz, 1 H, H-4), 7.06–7.79 (m,
9 H, ArH).
1H NMR (400 MHz, DMSO-d6 + D2O): d = 1.2 (s, 1 H, CH), 3.15
(ddd, J7,8 = 9.8 Hz, J1¢a,8 = 5.6 Hz, J1¢b,8 = 2.5 Hz, 1 H, H-8), 3.37
(dd, J6,7 = 9.5 Hz, J7,8 = 9.8 Hz, 1 H, H-7), 3.52 (dd, J1¢a,1¢b = 12.6
Hz, J1¢a,8 = 5.6 Hz, 1 H, Ha-1¢), 3.61 (dd, J6,7 = 9.5 Hz, J5,6 = 9.3 Hz,
1 H, H-6), 3.82 (dd, J1¢a,1¢b = 12.6 Hz, J1¢b,8 = 2.5 Hz, 1 H, H-1¢b),
4.16 (dd, J5,6 = 9.3 Hz, J4a,5 = 9.4 Hz, 1 H, H-5), 4.94 (dd, J4,4a = 9.6
Hz, J4a,5 = 9.4 Hz, 1 H, H-4a), 6.23 (d, J4,4a = 9.6 Hz, 1 H, H-4),
7.08–7.85 (m, 5 H, ArH).
13C NMR (DMSO-d6): d = 42.9, 48.2, 53.9, 61.1, 64.7, 65.9, 73.1,
114.7, 122.9, 125.8, 127.7, 128.6, 130.5, 137.4, 148.3, 163.9, 200.2.
MS (FAB): m/z = 441 [MH+].
13C NMR (DMSO-d6): d = 43.8, 50.6, 53.7, 60.2, 62.1, 64.5, 74.2,
128.6, 129.9, 131.4, 136.9, 163, 164.8, 201.
MS (FAB): m/z = 350 [MH+].
Anal. Calcd for C22H24N4O6: C, 59.99; H, 5.49; N, 12.72. Found: C,
60.18; H, 5.16; N, 12.94.
Anal. Calcd for C16H19N3O6: C, 55.01; H, 5.48; N, 12.03. Found: C,
55.31; H, 5.59; N, 11.80.
4-Aminopyrimidine Analogues 6 and 7; General Procedure
Compound 4 or 5 (2.0 mmol) was refluxed in H2SO4–H2O (15 mL,
4:3, v/v) for 45 min in an oil bath. The reaction mixture was cooled
and the desired products 6 or 7 were precipitated by adding concen-
trated NH4OH (specific gravity: 0.88) under ice cooling. The prod-
ucts were recrystallized from EtOH to obtain analytically pure
samples of 6 and 7.
N-{4,4a,5,6,7,8-Hexahydro-5,6,7-trihydroxy-8-(hydroxymeth-
yl)-3-oxo-1-phenyl-3H-pyrido[1,2-f]pyrimidin-4-yl}benzamide
(5d)
Pale-yellow powder; mp 127–129 °C.
IR (KBr): 3345, 3314, 3006, 2965, 1685, 1671, 1668, 1588, 1457,
738, 694 cm–1.
1H NMR (400 MHz, DMSO-d6 + D2O): d = 3.13 (ddd, J7,8 = 9.7 Hz,
J1¢a,8 = 5.9 Hz, J1¢b,8 = 2.4 Hz, 1 H, H-8), 3.35 (dd, J6,7 = 9.5 Hz,
J7,8 = 9.7 Hz, 1 H, H-7), 3.53 (dd, J1¢a,1¢b = 12.2 Hz, J1¢a,8 = 5.9 Hz,
1 H, H-1¢a), 3.67 (dd, J6,7 = 9.5 Hz, J5,6 = 9.3 Hz, 1 H, H-6), 3.81
(dd, J1¢a,1¢b = 12.2 Hz, J1¢b,8 = 2.4 Hz, 1 H, H-1¢b), 4.15 (dd, J5,6 = 9.3
Hz, J4a,5 = 9.4 Hz, 1 H, H-5), 4.98 (dd, J4,4a = 9.6 Hz, J4a,5 = 9.4 Hz,
1 H, H-4a), 6.22 (d, J4,4a = 9.5 Hz, 1 H, H-4), 7.08–7.85 (m, 10 H,
ArH).
13C NMR (DMSO-d6): d = 42.3, 53.6, 54.9, 60.2, 70.9, 72.3, 74.1,
125.7, 127.9, 129.0, 130.5, 131.9, 133.4, 135.8, 164.0, 200.9.
MS (FAB): m/z = 426 [MH+].
4-Amino-4,4a,5,6,7,8-hexahydro-5,6,7-trihydroxy-1-methyl-
pyrido[1,2-f]pyrimidin-3-one (6a)
Pale-yellow powder; mp 131–134 °C.
IR (KBr): 3343, 3011, 2895, 1683, 1670, 1604, 1581, 1451 cm–1.
1H NMR (400 MHz, DMSO-d6 + D2O): d = 0.8 (s, 3 H, Me), 2.63
(dd, J8ax,eq = 13.3 Hz, J7H,8ax = 9.7 Hz, 1 H, H-8ax), 3.34 (ddd,
J6,7 = 9.3 Hz, J8ax,7H = 9.7 Hz, J7H,8eq = 3.9 Hz, 1 H, H-7), 3.79 (dd,
J6,7 = 9.3 Hz, J5,6 = 9.1 Hz, 1 H, H-6), 3.94 (dd, J8ax,eq = 13.3 Hz,
J7H,8eq = 3.9 Hz, 1 H, H-8eq), 4.10 (dd, J5,6 = 9.1 Hz, J4a,5 = 9.4 Hz,
1 H, H-5), 5.03 (dd, J4,4a = 9.9 Hz, J4a,5 = 9.4 Hz, 1 H, H-4a), 6.16
(d, J4,4a = 9.9 Hz, 1 H, H-4).
13C NMR (DMSO-d6): d = 23.4, 41.6, 46.9, 57.1, 69.0, 71.2, 76.1,
164.4, 201.
Anal. Calcd for C22H23N3O6: C, 62.11; H, 5.45; N, 9.88. Found: C,
62.44; H, 5.71; N, 9.67.
MS (FAB): m/z = 230 [MH+].
N-{4,4a,5,6,7,8-Hexahydro-5,6,7-trihydroxy-8-(hydroxymeth-
yl)-1-(4-nitrophenyl)-3-oxo-3H-pyrido[1,2-f]pyrimidin-4-
yl}benzamide (5e)
Anal. Calcd for C9H15N3O4: C, 47.16; H, 6.60; N, 18.33. Found: C,
46.95; H, 6.91; N, 18.60.
Pale-yellow powder; mp 120–123 °C.
4-Amino-4,4a,5,6,7,8-hexahydro-5,6,7-trihydroxy-8-(hydroxy-
methyl)-1-methylpyrido[1,2-f]pyrimidin-3-one (7a)
Pale-yellow powder; mp 152–155 °C.
IR (KBr): 3342, 3319, 3008, 2963, 1684, 1675, 1669, 1588, 1457,
740, 692 cm–1.
1H NMR (400 MHz, DMSO-d6 + D2O): d = 3.16 (ddd, J7,8 = 9.9 Hz,
J1¢a,8 = 5.8 Hz, J1¢b,8 = 2.5 Hz, 1 H, H-8), 3.31 (dd, J6,7 = 9.4 Hz,
J7,8 = 9.9 Hz, 1 H, H-7), 3.56 (dd, J1¢a,1¢b = 12.5 Hz, J1¢a,8 = 5.8 Hz,
1 H, H-1¢a), 3.69 (dd, J6,7 = 9.4 Hz, J5,6 = 9.2 Hz, 1 H, H-6), 3.80
(dd, J1¢a,1¢b = 12.5 Hz, J1¢b,8 = 2.5 Hz, 1 H, H-1¢b), 4.12 (dd, J5,6 = 9.2
Hz, J4a,5 = 9.5 Hz, 1 H, H-5), 4.99 (dd, J4,4a = 9.7 Hz, J4a,5 = 9.5 Hz,
1 H, H-4a), 6.24 (d, J4,4a = 9.7 Hz, 1 H, H-4), 7.05–7.84 (m, 9 H,
ArH).
IR (KBr): 3345, 3014, 2952, 1681, 1673, 1579, 1449 cm–1.
1H NMR (400 MHz, DMSO-d6 + D2O): d = 0.9 (s, 3 H, Me), 3.15
(ddd, J7,8 = 9.8 Hz, J1¢a,8 = 6.1 Hz, J1¢b,8 = 2.3 Hz, 1 H, H-8), 3.37
(dd, J6,7 = 9.5 Hz, J7,8 = 9.8 Hz, 1 H, H-7), 3.55 (dd, J1¢a,1¢b = 12.2
Hz, J1¢a,8 = 5.7 Hz, 1 H, H-1¢a), 3.73 (dd, J6,7 = 9.5 Hz, J5,6 = 9.4 Hz,
1 H, H-6), 3.75 (dd, J1¢a,1¢b = 12.2 Hz, J1¢b,8 = 2.3 Hz, 1 H, H-1¢b),
4.10 (dd, J5,6 = 9.4 Hz, J4a,5 = 9.3 Hz, 1 H, H-5), 5.01 (dd, J4,4a = 9.5
Hz, J4a,5 = 9.3 Hz, 1 H, H-4a), 6.25 (d, J4,4a = 9.5 Hz, 1 H, H-4).
Synthesis 2009, No. 16, 2802–2808 © Thieme Stuttgart · New York

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Synthesis of Multifunctionalized Fused-Ring Pyrimidines
2807
13C NMR (DMSO-d6): d = 23.6, 44.9, 53.8, 57.1, 58.4, 68.6, 71.6,
74.2, 163.6, 201.
(3) (a) Horii, S.; Fukase, H.; Matsuo, T.; Kameda, Y.; Asano,
N.; Matsui, K. J. Med. Chem. 1986, 29, 1038.
(b) Robinson, K. M.; Begovic, M. E.; Reinhart, B. L.;
Heineke, E. W.; Ducep, J.-B.; Kastner, P. R.; Marshall, F.
N.; Danzin, C. Diabetes 1991, 40, 825.
MS (FAB): m/z = 260 [MH+].
Anal. Calcd for C10H17N3O5: C, 46.33; H, 6.61; N, 16.21. Found: C,
46.58; H, 7.90; N, 16.02.
(4) For a review, see: Asano, N. Glycobiology 2003, 13, 93R.
(5) Cipolla, L.; La Ferla, B.; Nicotra, F. Curr. Top. Med. Chem.
2003, 3, 485.
(6) (a) Nash, R. J.; Watson, A. A.; Asano, N. In Alkaloids:
Chemical and Biological Perspectives, Vol. 11; Pelletier, S.
W., Ed.; Elsevier: Oxford, 1996, 345–376. (b) Elbein, A.
D.; Molyneux, R. J. In Comprehensive Natural Products,
Vol. 3; Barton, D.; Nakanishi, K., Eds.; Elsevier: New York,
1999, 129–160.
(7) (a) Horii, S.; Fukase, H.; Mastsuo, T.; Kameda, Y.; Asano,
N.; Mastusi, K. Drugs Future 1986, 11, 1039. (b) Horii, S.;
Fukase, H.; Mastsuo, T.; Kameda, Y.; Asano, N.; Mastusi,
K. Drugs Future 1987, 12, 1157.
Isolation of Michael Adducts 9a (n = 3, R = Me) and 9g (n = 4,
R = Me) and Their Conversion into the Corresponding Sugar-
Annulated Pyrimidines 4a and 5a; General Procedure
The procedure followed was the same as described above for the
synthesis of 4 and 5, except that the time of MW irradiation in this
case was 4–6 min instead of 10–12 min for 4 and 5 (Table 2). The
adducts 9a and 9g were recrystallized from EtOH to give a diaste-
reomeric mixture (>98:<2); in the crude products the ratio was
>95:<5, as determined by 1H NMR spectroscopy. The mixture was
again recrystallized from EtOH to obtain analytically pure samples
of 9a and 9g. The adducts 9a and 9g were assigned the anti-stereo-
1
chemistry as their H NMR spectra exhibited larger coupling con-
(8) Cesar, J. J. Comb. Chem. 2005, 7, 517.
stants (JcyclicNCH,acyclicNCH = 9.9 Hz) than those of the very minor
(<6%) syn-diastereomer (JcyclicNCH,acyclicNCH = 4.4 Hz).25–31 An inti-
mate solvent-free mixture of 9a or 9g (2.0 mmol) and Montmorillo-
nite K-10 clay (0.20 g, particle size 32.7 nm) was taken in a 20 mL
vial and subjected to MW irradiation at 85 °C for 5–7 min to afford
the corresponding products 4a or 5a quantitatively, which were iso-
lated and purified as described above.
(9) (a) Hassan, N. A. Molecules 2000, 5, 827; and references
cited therein. (b) Pemmsin, M.; Lnu-Due, C.; Hoguet, F.;
Gaultier, C.; Narcisse, J. Eur. J. Med. Chem. 1988, 23, 453.
(c) Cannito, A.; Pemmsin, M.; Lnu-Due, C.; Hoguet, F.;
Gaultier, C.; Narcisse, J. Eur. J. Med. Chem. 1990, 25, 635.
(d) Smith, P. A. S.; Kan, R. O. J. Org. Chem. 1964, 29,
2261. (e) Nega, S.; Aionso, J.; Diazj, A.; Junquere, F. J.
Heterocycl. Chem. 1990, 27, 269. (f) Tetsuo, S.; Mikio, T.;
Hidetoshi, H.; Daijiro, H.; Akira, I. Jpn. Kokai Tokyo Koho
JP 62,132,884, 1987 Chem. Abstr. 1987, 107, 198350h.
(g) Chakaravorty, P. K.; Grelnlee, W. J.; Dooseap, K.;
Mantlo, N. B.; Patchett, A. A. A.P.C.T. Int. Appl.
WO9220687156, 1992; Chem. Abstr. 1993, 118, 213104d.
(h) Shishoo, C. J.; Jain, K. S. J. Heterocycl. Chem. 1992, 29,
883. (i) Jauk, B.; Belaj, F.; Kappe, C. O. J. Chem. Soc.,
Perkin Trans. 1 1999, 307.
(10) (a) Adlington, R. M.; Baldwin, J. A.; Catterick, D.;
Pritchard, G. J. J. Chem. Soc., Perkin Trans. 1 1999, 855;
references cited therein. (b) Rosenthal, G. A. Plant
Nonprotein Amino and Imino Acids Biological, Biochemical
and Toxicological Properties; Academic Press: New York,
NY, 1982, 117. (c) Bell, E. A. Biochim. Biophys. Acta 1961,
47, 602.
Characterization Data of Representative Compound 9a
Pale-yellow powder; mp 98–101 °C.
IR (KBr): 3145, 3015, 2892, 1772, 1678, 1601, 1583, 1456 cm–1.
1H NMR (400 MHz, DMSO-d6 + D2O): d = 1.4 (s, 3 H, Me), 4.09
(dd, J1¢,2¢ = 6.8 Hz, J1¢,acyclicNCH = 5.5 Hz, 1 H, H-1¢), 4.17 (dd,
J4¢Ha,Hb = 10.7 Hz, J4¢Hb,3¢ = 5.6 Hz, 1 H, Hb-4¢), 4.36 (dd, J1¢,2¢ = 6.8
Hz, J2¢,3¢ = 4.3 Hz, 1 H, H-2¢), 4.69 (ddd, J3,4¢Hb = 5.6 Hz, J3,4¢Ha = 5.2
Hz, J2¢,3¢ = 4.3 Hz, 1 H, H-3¢), 4.81 (dd, J4¢Ha,Hb = 10.7 Hz,
J3,4¢Ha = 5.2 Hz, 1 H, Ha-4¢), 5.01 (dd, J1¢,acyclicNCH = 5.5 Hz,
JcyclicNCH,acyclicNCH = 10.1 Hz, 1 H, NCHacyclic), 6.77 (d,
JcyclicNCH,acyclicNCH = 10.1 Hz, 1 H, NCHcyclic), 7.10–7.67 (m, 5 H
ArH).
13C NMR (DMSO-d6): d = 26.1, 44.9, 58.9, 64.7, 70.7, 72.1, 73.5,
127.5, 128.8, 131.2, 136.4, 164.5, 167.6, 175.1.
(11) (a) Brown, D. J. In The Chemistry of Heterocyclic
Compounds: The Pyrimidines, Vol. 16; Weissberger, A.,
Ed.; Wiley-Interscience: New York, 1970. (b) Brown, D. J.
In Comprehensive Heterocyclic Chemistry, Vol. 3;
Katritzky, A. R.; Rees, C. W., Eds.; Pergamon Press:
Oxford, 1984, Chap. 2.13. (c) Eicher, T.; Hauptmann, S.
Chemie der Heterocyclen; Georg Thieme Verlag: Stuttgart,
New York, 1994, 398. (d) Gilchrist, T. L.
MS (FAB): m/z = 352 [MH+].
Anal. Calcd for C16H21N3O6: C, 54.69; H, 6.02; N, 11.96. Found: C,
54.52; H, 6.23; N, 12.25.
Acknowledgment
We sincerely thank DST, Govt. of India, for financial support (DST
File No. SR/S1/OC-65/2006), and SAIF, Punjab University, Chan-
digarh, for providing microanalyses and spectra.
Heterocyclenchemie; Neunhoeffer, H., Ed.; Wiley-VCH:
New York, 1995, 270.
(12) (a) Lehn, J.-M. Supramolecular Chemistry-Concepts and
Perspectives; VCH: Weinheim, 1995, Chap. 9. (b) Hanan,
G. S.; Volkmer, D.; Schubert, U. S.; Lehn, J.-M.; Baum, G.;
Fenske, D. Angew. Chem. Int. Ed. 1997, 36, 1842.
(c) Semenov, A.; Spatz, J. P.; Möller, M.; Lehn, J.-M.; Sell,
B.; Schubert, D.; Weidl, C. H.; Schubert, U. S. Angew.
Chem. Int. Ed. 1999, 38, 2547.
(13) (a) Harriman, A.; Ziessel, R. Coord. Chem. Rev. 1998, 171,
331. (b) Harriman, A.; Ziessel, R. Chem. Commun. 1996,
1707.
(14) (a) Taylor, E. C.; Knoff, R. J.; Meyer, R. F.; Holmes, A.;
Hoefle, M. L. J. Am. Chem. Soc. 1960, 82, 5711. (b) Inoue,
S.; Saggiomo, A. J.; Nodiff, E. A. J. Org. Chem. 1961, 26,
4504. (c) Bredereck, H.; Effenberger, F.; Botsch, H.; Rehn,
H. Chem. Ber. 1965, 98, 1081. (d) Chauhan, S. M. S.;
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Synthesis 2009, No. 16, 2802–2808 © Thieme Stuttgart · New York

2808
L. D. S. Yadav, A. Rai
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Synthesis 2009, No. 16, 2802–2808 © Thieme Stuttgart · New York