Unexpected dimerization during hydrogenation of 2-(2-pyridylmethylene)-3(2H)-benzofuran-3-ones

Article abstract of DOI:10.1016/j.tet.2006.06.016

Palladium catalyzed hydrogenation of 2-(2-pyridylmethylene)-3(2H)-benzofuran-3-ones (1-3) gave besides the expected 2,α-dihydro products 8-10 pentacyclic dimers formed by an attack of a semihydrogenated species on the substrate.

Full text of DOI:10.1016/j.tet.2006.06.016

Tetrahedron 62 (2006) 8425–8429
Unexpected dimerization during hydrogenation of
2-(2-pyridylmethylene)-3(2H)-benzofuran-3-ones
a
b,
c
ꢀ
*
ꢀ
ꢀ
ꢀ ꢀ
€
Marianna Mak, Mihaly Nogradi and Aron SzollTsy
aDepartment of Structural Research, Gedeon Richter Ltd, PO Box 27, H-1475 Budapest, Hungary
bInstitute for Organic Chemistry, Budapest University of Technology and Economics, PO Box 91, H-1521 Budapest, Hungary
cInstitute for General and Analytical Chemistry, Budapest University of Technology and Economics,
PO Box 91, H-1521 Budapest, Hungary
Received 9 March 2006; revised 18 May 2006; accepted 1 June 2006
Available online 7 July 2006
Abstract—Palladium catalyzed hydrogenation of 2-(2-pyridylmethylene)-3(2H)-benzofuran-3-ones (1–3) gave besides the expected 2,a-di-
hydro products 8–10 pentacyclic dimers formed by an attack of a semihydrogenated species on the substrate.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
uptake completely stopped after the absorption of approxi-
mately 60% of the theoretically calculated volume. Chro-
matography of the product gave, apart from the expected
6-methoxy-2-(2-pyridylmethyl)-3(2H)-benzofuran-3-one (9),
a substance with a mp 180 ꢀC that even after several recrys-
tallizations showed two complete sets of 1H NMR signals in
a 1:1 intensity ratio for the aromatic protons of the benzo-
furan and pyridine rings, as well as signals for a contiguous
set of three aliphatic protons.
For testing purposes a series of 2-(2-pyridylmethylene)-
3(2H)-benzofuran-3-ones (4–6) were prepared by condensa-
tion of 3(2H)-benzofuran-3-ones (1–3) with pyridine-2-
aldehyde in the presence of morpholine acetate (Scheme 1).1
R1
R1
O
O
CHO
H2
N
N
N
Pd/C, EtOH
R2O
O
R2O
O
.
AcOH
O
1
2
2. Results and discussion
2.1. Structural studies
1
2
4: R = H, R = H
1: R = H, R = H
2: R = H, R = Me
3: R = Me, R = H
1
2
1
2
5: R = H, R = Me
1
2
1
2
6: R = Me, R = H
7: R = R = Me
1
2
8
R1O
4"
N
8a
7
H
H
O
Detailed spectroscopic studies summarized in Table 1
showed that the by-product of the hydrogenation of com-
pound 5 was a dimer of structure 12 (see Scheme 1) in which
one of the carbonyl groups was transformed into an alcohol.
1H–1H connectivities and the presence of five different spin
systems were observed in the 1H–1H COSY spectrum, which
also permitted complete 1H signal assignment. The position
of the H-5 signal (d 6.57 ppm) indicated that, when compared
to that of H-40 (d 7.50 ppm), H-5 was not peri to a carbonyl
group. Furthermore, there was only one signal in the 13C
NMR spectrum, which could be assigned to a ketone.
Long-range 1H–13C connectivities (HMBC spectrum) of the
quaternary 13C signals at 97.3 and 92.5 ppm (assigned to C-3
and C-4) gave further evidence for the postulated structure
(12). The NOESY spectrum suggested that there was no
steric proximity neither between H-1 and H-2 nor between
H-1 and H-10. This indicated a trans–trans disposition, which
was in agreement with the measured 3J coupling constants.
R2O
5"
10
O
4
6
5
R2H
1
6"
N
H
4a
N
3"'
3
O
2
+
4"'
1
O
2
O
R
1
3a'
O
7a'
7'
6"'
5"'
3b'
4'
5'
8: R = H, R = H
R2
1
2
1
2
9: R = H, R = Me
11: R = H, R = H
1
2
1
2
10: R = Me, R = Me
6'
12: R = Me, R = H
OR1
1
2
13: R = Me, R = Me
Scheme 1.
Alkene 5 was subjected to catalytic hydrogenation over pal-
ladium-on-charcoal in ethanol. Owing to its poor solubility
the substrate was added as a solid to the ethanolic suspension
of the prehydrogenated catalyst. Unexpectedly hydrogen
Keywords: 2-Pyridylmethylene-3(2H)-benzofuran-3-ones; Hydrogenation;
Dimerization.
* Corresponding author. E-mail: nogradi@mail.bme.hu
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.06.016

8426
M. Maꢀk et al. / Tetrahedron 62 (2006) 8425–8429
Table 1. NMR data for compound 12
Position
dH, Multiplicities, intensities,
and coupling constants
1H–1H COSY cross-peaks
dC
Significant HMBC correlations
of the 13C signal
1
2
3
4
4a
5
6
7
8
4.63, dd, (1H), 12.8, 6.5 Hz
4.88, d, (1H), 12.8 Hz
2-H, 10-H
1-H
54.2
58.0
97.3
2-H, 600-H
1-H, 6000-H
2-H, 10-H
5-H, 10-H
6-H, 8-H
92.5
117.9
124.1
107.6
162.2
96.4
6.56, d, (1H), 8.3 Hz
6.26, dd, (1H), 8.3, 2.0 Hz
6-H
5-H, 8-H
8-H
5-H, 6-H, 8-H
5-H, 6-H
6.42, d, (1H), 2 Hz
5.35, d, (1H), 6.5 Hz
6-H
1-H
8a
10
3a0
3b0
40
162.5
99.2
5-H, 6-H, 8-H, 10-H
1-H, 2-H
198.0
114.8
125.1
112.4
168.8
95.5
174.1
158.7
149.8
122.1
136.4
124.3
153.4
148.8
122.3
136.0
123.8
2-H, 50-H
40-H, 50-H, 70-H
7.49, d, (1H), 8.8 Hz
6.52, dd, (1H), 8.8, 2.0 Hz
50-H
40-H, 70-H
50
40-H, 70-H
60
40-H, 70-H, OCH3
40-H
70
6.10, d, (1H), 2.0 Hz
50-H
70a00
100
300
400
500
6000
1
40-H, 70-H
1-H, 2-H, 10-H, 400-H
400-H, 500-H
8.59, dd, (1H), 4.9, 1.9 Hz
7.10, dd, (1H), 7.5, 4.9 Hz
7.55, ddd, (1H), 7.5, 7.5, 1.9 Hz
7.39, d, (1H), 7.5 Hz
7.10
8.59, 7.55
7.10, 7.39
7.55
300-H
1-H, 2-H, 4000-H
4000-H, 5000-H
3000
4000
5000
6000
OH
OCH3
8.33, dd, (1H), 5.2, 1.5 Hz
6.91, dd, (1H), 7.5, 5.2 Hz
7.32, ddd, (1H), 7.5, 7.5, 1.5 Hz
7.06, d, (1H), 7.5 Hz
5.15, br s, (1H)
6.91
8.33, 7.32
6.91, 7.06
7.32
3000-H
3.74, s, (3H)
3.71, s, (3H)
55.7
56.1
0
OCH3
A total of 32 13C signals was observed, that confirmed the di-
meric structure of 12. Total signal assignment was possible
on the basis of HMBC connectivities.
O
O
O
H
H
H
.
H
.
H
H
Py
O
O
Py
O
Py
MeO
Py
O
O
MeO
MeO
H
H
+
5 (Py = 2-pyridyl)
.
Py
Chelation between the carbonyl and hydroxyl groups was in-
dicated by a slowly developing color reaction with iron(III)
O
O
chloride2 and a bathochromic shift (nCO 1704/1672 cmꢁ1
)
MeO
MeO
MeO
of the carbonyl absorption3 relative to that in the parent com-
pound (2) enabling the assignment of the disposition of the
spiro system.
MeO
H
O
O
H
H
H
Py
H
Py
.
O
Py
.
H
O
H
13
O
O
O
Finally mass spectrometry indicated for 12 a molecular mass
of 508 corresponding to 2ꢂ5+2ꢂH.
.
Py
O
OMe
2.2. Investigations on other systems
MeO
Scheme 2. Tentative mechanism for the formation of dimer 8.
Hydrogenation of compounds 4 and 7 proceeded similarly
and provided along with the normal products (i.e., 8 and
10) the dimers 11 and 13 both showing in their H NMR
spectra the duplication of the aromatic and pyridine signals,
as well as signals for H-1, H-2, and H-10.
1
This mechanism is in conflict with the still widely accepted
classical concept proposed more than 70 years ago by Hori-
4,5
ꢀ
uti and Polanyi. This postulates that the olefin adsorbed
with its p-bond to the catalyst surface assumes, after the
addition of one hydrogen atom a half-hydrogenated state,
followed by the uptake of the second hydrogen atom. Even
if the nature of the interaction of the olefin and the catalyst
surface is disputed (dissociative or associative adsorption)
it is supposed that the half-hydrogenated species remains
on the catalyst until complete saturation.
Although reactions other than p-bond saturation, such as
hydrogen exchange, double bond migration, and cis–trans
isomerization have been reported,4 to our knowledge no
intermolecular reactions accompanying catalytic hydro-
genation have been observed.
A tentative mechanism shown in Scheme 2 is proposed for
the formation of the dimers as exemplified by the transfor-
mation of 5/11.
Our results suggest that there exists a usually latent path-
way along with the classical mechanism through which

M. Maꢀk et al. / Tetrahedron 62 (2006) 8425–8429
8427
a half-hydrogenated radical species can attack the olefin pre-
cursor. The question whether this occurs in solution or on the
surface of the catalyst and how is the second hydrogen atom
transferred to the dimeric radical remains open.
and morpholine acetate (0.6 g) was boiled with stirring in
methanol (20 mL) for 2 h. The product was filtered off hot
and washed with methanol to give pure 4 as yellow needles
(3.5 g, 74%), mp 278–280 ꢀC. nmax 3440, 2352, 1704,
1600, 1564, 1456, 1424, 1400, 1344, 1304, 1252, 1224,
1216, 1152, 1104, 1008, 960, 944, 872, 832, 776, 680, 628,
496, 456 cmꢁ1; dH (DMSO-d6) 6.68 (s, 1H, a-H), 6.74 (dd,
J 8.2, 1.9 Hz, 1H, 5-H), 6.80 (d, J 1.9 Hz, 1H, 7-H), 7.39
(dd, J 7.5, 4.5 Hz, 1H, 40-H), 7.65 (d, J 7.5 Hz, 1H, 60-H),
7.92 (ddd, J 7.5, 7.5, 1.5 Hz, 1H, 50-H), 8.15 (d, J 8.2 Hz,
1H, 4-H), 8.68 (dd, J 4.5, 1.5 Hz, 1H, 30-H). Anal. Calcd
for C14H9NO3: C, 70.29; H, 3.79; N, 5.86. Found: C, 70.08;
H, 3.86; N, 5.70.
The scope of the above dimerization seems to be very
narrow. Hydrogenation of 6-hydroxy-2-(3-pyridylmethyl-
ene)-3(2H)-benzofuran-3-one (14), 6-methoxy-2-(4-pyri-
dylmethylene)-3(2H)-benzofuran-3-one (15), 6-hydroxy-
2-(4-hydroxybenzylidene)-3(2H)-benzofuran-3-one6 (16),
and even of 2-(2-pyridylmethylene)-1-tetralone (17) (Fig. 1)
only gave the regular dihydro products.
3.1.3. 6-Methoxy-2-(2-pyridylmethylene)-3(2H)-benzo-
furan-3-one (5). Condensation of 6-methoxy-3(2H)-benzo-
furan-3-one8 (2) with pyridine-2-aldehyde as described
under 4 gave the title compound as yellow needles in 70%
yield, mp 155–157 ꢀC (from EtOH); nmax 3432, 1704,
1616, 1504, 1440, 1328, 1280, 1196, 1152, 1128, 1104,
1016, 960, 888, 816, 776, 760, 544 cmꢁ1; dH (CDCl3) 3.93
(s, 3H, OMe), 6.75 (dd, J 8.2, 1.5 Hz, 1H, 5-H), 6.78 (s,
1H, a-H), 6.95 (d, J 1.5 Hz, 1H, 7-H), 7.25 (m, 1H, 40-H),
7.72 (d, J 7.5 Hz, 1H, 60-H), 7.78 (ddd, J 7.5, 7.5, 1.5 Hz,
1H, 50-H), 8.09 (d, J 8.2 Hz, 1H, 4-H), 8.73 (dd, J 4.5,
1.5 Hz, 1H, 30-H); d13 56.3, 76.8, 77.2, 77.4, 77.6, 97.2,
111.5, 112.6, 114.7, 123.3, 126.2, 126.7, 136.7, 149.4, 150.4,
152.4, 167.9, 169.5, 183.1; FABMS (NBA): MH+ 254,
daughter ions: m/z 239, 226. Anal. Calcd for C15H11NO3:
C, 71.14; H, 4.38; N, 5.53. Found: C, 71.28; H, 4.42; N, 5.61.
O
O
N
O
15
O
14
MeO
HO
N
O
O
N
O
16
HO
17
OH
Figure 1.
3. Experimental
3.1. General
Infrared spectra were recorded on a Zeiss Specord IR 74
spectrometer as KBr pellets, 1H (500 MHz) and 13C
(125 MHz) spectra were recorded on a Bruker DRX/Avance
spectrometer. Fast atom bombardment (FAB/LSIMS) and
daughter ion spectra were performed on a Finnigan MAT
95SQ hybrid tandem mass spectrometer. The Cs+ gun was
used at 20 kVand the matrix applied was 3-nitrobenzyl alco-
hol (NBA). For chromatography silica gel 60 (Merck) was
used.
3.1.4. 6-Hydroxy-4-methyl-2-(2-pyridylmethylene)-
3(2H)-benzofuran-3-one (6). Condensation of 6-hydroxy-
4-methyl-3(2H)-benzofuran-3-one (3) with pyridine-2-alde-
hyde as described for 4 gave the title compound as small
yellow needles in 43% yield, mp 294–296 ꢀC. nmax 3440,
1696, 1664, 1616, 1580, 1472, 1352, 1288, 1184, 1152,
1052, 1008, 840, 784, 688, 628, 544 cmꢁ1; dH (DMSO-d6)
2.48 (s, 3H, Me), 6.47 and 6.53 (2ꢂd, J 2.0 Hz, 2H, 5- and
7-H), 6.60 (s, 1H, a-H), 7.31 (dd, J 7.5, 4.5 Hz, 1H, 40-H),
7.80 (ddd, J 7.5, 7.5, 1.0 Hz, 1H, 50-H), 8.15 (d, J 7.5 Hz,
1H, 60-H), 8.86 (dd, J 4.5, 1.0 Hz, 1H, 30-H). Anal. Calcd
for C15H11NO3: C, 71.14; H, 4.38; N, 5.53. Found: C,
71.06; H, 4.42; N, 5.62.
3.1.1. 6-Hydroxy-4-methyl-3(2H)-benzofuran-3-one (3).
To a solution of orcinol (7.44 g, 60 mmol) and chloroaceto-
nitrile (3.7 mL, 58 mmol) in dry diethyl ether (40 mL) was
added powdered anhydrous zinc chloride (5 g). The mixture
was cooled to 0 ꢀC and saturated with hydrogen chloride gas.
The next day the ether was decanted from the precipitated
gummy imine hydrochloride. The rest of the solvent was re-
moved in vacuo and the salt treated boiling water (300 mL).
After cooling the precipitate was collected by filtration and
dried to give the chloroketone (8.5 g). Without purification
the latter was boiled for 15 min with potassium acetate
(10 g) in methanol (75 mL). On cooling the product crystal-
lized as needles (5.4 g, 77%), mp 245 ꢀC. nmax 3064, 1664,
1616, 1468, 1388, 1328, 1280, 1264, 1252, 1152, 1116,
1060, 1020, 856, 820, 768, 616, 528, 488 cmꢁ1; dH
(DMSO-d6) 2.41 (s, 3H, Me), (4.63, s, 2H, 2-H), 6.30 and
6.32 (2ꢂs, 2H, 4,6-H), 10.77 (br s, 1H, OH). Anal. Calcd
for C9H8O3: C, 65.85; H, 4.91. Found: C, 65.72; H, 4.96.
3.1.5. 6-Methoxy-4-methyl-2-(2-pyridylmethylene)-
3(2H)-benzofuran-3-one (7). 6-Hydroxy-4-methyl-2-(2-
pyridylmethylene)-3(2H)-benzofuran-3-one (6) (0.97 g,
3.8 mmol) was stirred in dry acetone (50 mL) in the pres-
ence of dry sodium hydrogen carbonate (2.4 g, 28 mmol)
and dimethyl sulfate (0.4 mL, 4.3 mmol) for 24 h. Filtration
and evaporation of the filtrate, and recrystallization of the
residue from EtOH (14 mL) gave 7 as pale yellow needles
(0.51 g, 50%), mp 168–169 ꢀC. nmax 2328, 1704, 1616,
1484, 1460, 1352, 1304, 1264, 1216, 1208, 1196, 1148,
1076, 1060, 1008, 832, 788, 768, 608, 544, 408 cmꢁ1; dH
(CDCl3) 2.62 (s, 3H, Me), 3.86 (s, 3H, OMe), 6.48 and
6.60 (2ꢂd, J 2.0 Hz, 1H, 5- and 7-H), 6.90 (s, 1H, a-H),
7.19 (dd, J 7.5, 4.5 Hz, 1H, 40-H), 7.73 (ddd, J 7.5, 7.5,
1.0 Hz, 1H, 50-H), 8.08 (d, J 7.5 Hz, 1H, 60-H), 8.70 (dd,
J 4.5, 1.0 Hz, 1H, 30-H). Anal. Calcd for C16H13NO3:
C, 71.90; H, 4.90; N, 5.24. Found: C, 71.93; H, 4.82;
N, 5.30.
3.1.2. 6-Hydroxy-2-(2-pyridylmethylene)-3(2H)-benzo-
furan-3-one (4). 6-Hydroxy-3(2H)-benzofuran-3-one7 (1)
(3.3 g, 22 mmol), pyridine-2-aldehyde (2.4 g 22 mmol),

8428
M. Maꢀk et al. / Tetrahedron 62 (2006) 8425–8429
3.1.6. 6-Hydroxy-2-(2-pyridylmethyl)-3(2H)-benzo-
furan-3-one (8) and rel-1S,2S,3S,4S,10R-spiro[4,7-
dihydroxy-1,2-bis-2-pyridyl-1,2,3,4-tetrahydro-1H-9-oxa-
cyclopenta[a]indene-20-(6-hydroxy-3(2H)-benzofuran-
3-one)] (11). Hydrogenation of 4 (1.08 g, 5 mmol) was
performed as described below (compound 9). Extraction of
the crude product with hot acetone (20 mL) gave 8 as color-
less plates (0.35 g, 33%), mp 205–208 ꢀC. Evaporation of
the mother liquor yielded the dimer 11 as an amorphous
powder (0.23 g, 21%), mp 203–204 ꢀC.
Compound 12: nmax 3368, 3064, 3032, 3008, 1672, 1608,
1592, 1500, 1472, 1444, 1288, 1276, 1260, 1200, 1152,
1104, 1064, 1008, 760, 584 cmꢁ1; dH (CDCl3) 3.71 and
3.74 (2ꢂs, 2ꢂ3H, 2ꢂOMe), 4.63 (dd, J 12.8, 6.5 Hz, 1H,
1-H), 4.88 (d, J 12.8 Hz, 1H, 2-H), 5.15 (br s, 1H, OH),
5.35 (d, J 6.5 Hz, 1H, 10-H), 6.10 (d, J 2.0 Hz, 1H, 70-H),
6.26 (d, J 8.3, 2.0 Hz, 1H, 6-H), 6.42 (d, J 2.0 Hz, 1H, 8-
H), 6.52 (dd, J 8.8, 2.0 Hz, 1H, 50-H), 6.56 (d, J 8.3 Hz,
1H, 5-H), 6.91 (dd, J 7.5, 5.2 Hz, 1-H, 4000-H), 7.06 (d, J
7.5, 1H, 6000-H) 7.10 (dd, J 7.5, 4.9 Hz, 1H, 400-H), 7.32
(ddd, J 7.5, 7.5, 1.5 Hz, 1H, 5000-H), 7.39 (d, J 7.5, 1H, 600-
H), 7.49 (d, J 8.8 Hz, 1H, 40-H), 7.55 (ddd, J 7.5, 7.5,
1.5 Hz, 1H, 500-H), 8.33 (dd, J 5.2, 1.5 Hz, 1H, 3000-H), 8.59
(dd, J 4.9, 1.9 Hz, 1H, 300-H); d13 (CDCl3) 54.2 (C-1), 55.7
(OMe), 56.1 (OMe), 58.0 (C-2), 92.5 (C-4), 95.5 (C-70),
96.4 (C-7), 97.3 (C-3), 99.2 (C-9), 107.6 (C-5), 112.4 (C-
50), 114.8 (C-3b0), 117.9 (C-3b), 122.1 (C-400), 122.3 (C-
4000), 123.8 0(00C-6000), 124.1 0(0C-4), 124.3 (C-600), 125.1 (C-40),
136.0 (C-5 ), 136.4 (C-5 ), 148.77 (C-3000), 148.83 (C-300),
153.4 (C-1000), 158.7 (C-100), 162.2 and 162.5 (C-6 and C-
7a), 168.8 (C-60), 174.1 (C-7a0), 198.0 (C-3a0); FABMS
(NBA): MH+ 509, daughter ions: m/z 519, 268. Anal. Calcd
for C30H24N2O6: C, 70.86; H, 4.76; N, 5.51. Found: C,
70.90; H, 4.80; N, 5.55.
Compound 8: nmax 3424, 3248, 1700, 1612, 1484, 1416,
1328, 1320, 1312, 1264, 1152, 1104, 1072, 1012, 840,
808, 768, 648, 544 cmꢁ1; dH (DMSO-d6) 3.03 (dd, J 14.5,
9.5 Hz, 1H, a-H1), 3.22 (dd, J 14.5, 3.8 Hz, 1H, a-H2),
5.16 (dd, J 9.5, 3.8 Hz, 1H, 2-H), 6.42 (d, J 1.9 Hz, 1H,
7-H), 6.56 (dd, J 8.8, 1.9 Hz, 1H, 4-H), 7.24 (dd, J 7.5,
5.5 Hz, 1H, 40-H), 7.33 (d, J 7.5 Hz, 1H, 60-H), 7.46 (d,
J 8.8 Hz, 1H, 4-H), 7.72 (ddd, J 7.5, 7.5, 1.5 Hz, 1H, 50-
H), 8.48 (dd, J 5.5, 1.5 Hz, 1H, 30-H). Anal. Calcd for
C14H11NO3: C, 69.70; H, 4.60; N, 5.81. Found: C, 69.67;
H, 4.63; N, 5.86.
Compound 11: dH (DMSO-d6) 4.30 (dd, J 13.2, 6.9 Hz, 1H,
1-H), 4.65 (d, J 13.2 Hz, 1H, 2-H), 5.06 (d, J 6.9 Hz, 1H, 10-
H), 5.71 (br s, 1H, 70-H), 6.14 (dd, J 8.5, 1.9 Hz, 1H, 6-H),
6.24 (d, J 1.9 Hz, 1H, 8-H), 6.26 (dd, J 8.5, 1.9 Hz, 1H,
50-H), 6.42 (d, J 8.5 Hz, 1H, 5-H), 6.97 (dd, J 7.5, 4.5 Hz,
1H, 4000-H), 7.09 (dd, J 7.5 Hz, 1H, 6000-H), 7.19 (dd, J 7.5,
4.5 Hz, 1H, 400-H), 7.26 (d, J 7.5 Hz, 1H, 600-H), 7.37 (d,
J 8.5 Hz, 1H, 40-H), 7.43 (dd, J 7.5, 7.5 Hz, 1H, 5000-H),
7.65 (dd, J 7.5, 7.5 Hz, 1H, 500-H), 8.33 (d, J 4.5 Hz, 1H,
3000-H), 8.53 (d, J 4.5 Hz, 1H, 300-H). Anal. Calcd for
C28H20N2O6: C, 69.99; H, 4.20; N, 5.83. Found: C, 69.80;
H, 4.18; N, 5.80.
3.1.8. 6-Methoxy-4-methyl-2-(2-pyridylmethyl)-3(2H)-
benzofuran-3-one (10) and rel-1S,2S,3S,4S,10R-spiro[4-
hydroxy-7-methoxy-5-methyl-1,2-bis-2-pyridyl-1,2,3,3a-
tetrahydro-1H-8-oxacyclopenta[a]indene-20-(6-meth-
oxy-4-methyl-3(2H)-benzofuran-3-one)] (13). Hydroge-
nation of 7 (396 mg, 1.48 mmol) was performed as
described for 5. Chromatography of the crude product (elu-
ant: PhMe–EtOAc, 2:1) gave 10 as colorless needles
(119 mg, 30%), mp 76–78 ꢀC and (13) as an amorphous
powder (83 mg, 21%), mp 247–248 ꢀC.
3.1.7. Hydrogenation of 6-methoxy-2-(2-pyridylmethy-
lene)-3(2H)-benzofuran-3-one (5): 6-methoxy-2-(2-pyri-
dylmethyl)-3(2H)-benzofuran-3-one (9) and rel-1S,
2S,3S,4S,10R-spiro[4-hydroxy-7-methoxy-1,2-bis-2-pyr-
idyl-1,2,3,4-tetrahydro-1H-9-oxacyclopenta[a]indene-20-
(6-methoxy-3(2H)-benzofuran-3-one)] (12). Palladium-
on-carbon, (10%, 0.5 g) was prehydrogenated in ethanol
(100 mL). The apparatus was opened, 5 (3.0 g, 11.8 mmol)
was added as a solid and flushed with hydrogen. After rapid
initial absorption hydrogen uptake stopped at about 60% of
the theoretical amount (283 mL). After filtration and evapo-
ration of the filtrate the residue was chromatographed
(eluant: benzene–ethyl acetate, 2:1) to give 6-methoxy-2-
(2-pyridylmethyl)-3(2H)-benzofuran-3-one (9) as colorless
plates (0.7 g, 23%), mp 103–105 ꢀC (from Et2O) and the di-
mer 12 as colorless plates (0.31 g, 10%), mp 180–182 ꢀC.
Compound 10: nmax 3384, 3024, 1656, 1616, 1456, 1440,
1352, 1344, 1332, 1316, 1272, 1200, 1148, 1052, 1040,
944, 808, 752, 696, 544, 496 cmꢁ1; dH (CDCl3) 2.52 (s,
3H, CH3), 3.08 (dd, J 15.5, 9.5 Hz, 1H, a-H1), 3.53 (dd, J
15.5, 3.5 Hz, 1H, a-H2), 3.81 (s, 3H, OCH3), 5.09 (dd, J 9.5,
3.5 Hz, 1H, 2-H), 6.34 (d, J 2.0 Hz, 1H, 6-H), 6.37 (m, 1H,
4-H), 7.16 (dd, J 7.5, 5.5 Hz, 1H, 40-H), 7.25 (d, J 7.5 Hz,
1H, 60-H), 7.63 (ddd, J 7.5, 7.5, 1.5 Hz, 1H, 50-H), 8.57
(dd, J 5.5, 1.5 Hz, 1H, 30-H). Anal. Calcd for C16H15NO3:
C, 71.36; H, 5.61; N, 5.20. Found: C, 71.24; H, 5.42; N, 5.41.
Compound 13: nmax 3424, 3240, 2592, 1960, 1700, 1648,
1616, 1516, 1484, 1428, 1416, 1356, 1312, 1288, 1168,
1152, 1124, 1104, 1084, 1072, 1028, 1012, 976, 904, 860,
840, 820, 808, 792, 768, 760, 752, 660, 648, 636, 624,
612, 596, 584, 576, 520, 504, 464, 440, 428 cmꢁ1; dH
(CDCl3) 2.15, 2.50 (2ꢂs, 2ꢂMe, 6H), 3.71, 3.73 (2ꢂs,
2ꢂOMe, 6H), 4.63 (dd, J 13.0, 6.5 Hz, 1H, 1-H), 4.81 (d,
J 13.0 Hz, 1H, 2-H), 5.31 (d, J 6.5 Hz, 1H, 10-H), 5.64
(br s, 1H, OH), 5.98 (d, J 2.0 Hz, 1H, 70-H), 6.09 (m, 1H,
6-H), 6.21 (m, 1H, 50-H), 6.24 (d, J 2.0 Hz, 1H, 8-H),
6.90 (ddd, J 7.5, 5.0, 1.5 Hz, 1H, 4000-H), 7.05–7.10 (m,
2H, 400- and 6000-H), 7.31 (ddd, J 7.5, 7.5, 1.5 Hz, 1H, 5000-
H), 7.36 (d, J 7.5 Hz, 1H, 600-H), 7.63 (ddd, J 7.5, 7.5,
2.0 Hz, 1H, 500-H), 8.32 (dd, J 5.0, 1.5 Hz, 1H, 300-H),
8.58 (dd, J 5.0, 1.5 Hz, 1H, 300-H); FABMS (NBA): MH+
537, daughter ions: m/z 519, 268. Anal. Calcd for
Compound 9: nmax 2928, 2384, 1620, 1508, 1444, 1376,
1252, 1156, 1028, 784, 616 cmꢁ1; dH (CDCl3) 3.11 (dd,
J 15.5, 9.5 Hz, 1H, a-H1), 3.14 (dd, J 15.5, 3.5 Hz, 1H,
a-H2), 3.84 (s, 3H, OMe), 5.16 (dd, J 9.5, 3.5 Hz, 1H, 2-H),
6.59 (d, J 1.5 Hz, 1H, 7-H), 6.63 (dd, J 8.5, 1.5 Hz, 1H,
5-H), 7.17 (dd, J 7.5, 5 Hz, 1H, 40-H), 7.24 (d, J 7.5 Hz,
1H, 60-H), 7.57 (d, J 8.5 Hz, 1H, 4-H), 7.62 (ddd, J 7.5,
7.5, 1.5 Hz, 1H, 50-H), 8.57 (dd, J 5, 1.5 Hz, 1H, 30-H).
Anal. Calcd for C15H13NO3: C, 70.58; H, 5.13; N, 5.49.
Found: C, 70.62; H, 5.02; N, 5.45.

M. Maꢀk et al. / Tetrahedron 62 (2006) 8425–8429
8429
2. Mabry, T. J.; Markham, K. R.; Thomas, M. B. The Systematic
Identification of Flavonoids; Springer: Berlin; Heidelberg;
New York, NY, 1970; p 52.
C32H28N2O6: C, 71.63; H, 5.26; N, 5.22. Found: C, 71.70;
H, 5.32; N, 5.18.
3. March, J. Advanced Organic Chemistry, 5th ed.; Wiley:
New York, NY, 2001; p 100.
Acknowledgements
4. Smith, G. V.; Notheisz, F. Heterogeneous Catalysis in Organic
Chemistry; Academic: San Diego, 1999; p 72.
Helpful discussions with Drs. J. Kuszmann and Gy.
}
M. Keseru are gratefully acknowledged. We thank OTKA
(Grant no. T046127) for financial support.
ꢀ
5. Horiuti, I.; Polanyi, M. Trans. Faraday Soc. 1934, 30, 1164.
6. Breitenbach, J. C.; Rall, G. J. H.; Roux, D.; Hall, W. E. J.
J. Chem. Soc., Perkin Trans. 1 1982, 1157.
References and notes
7. Slater, W. K.; Stephen, H. J. Chem. Soc. 1920, 117, 314.
8. Doifode, K. B.; Marathey, M. G. J. Org. Chem. 1964, 29,
2025.
1. Katritzky, A. R.; Kennewell, P. D.; Snarez, M. J. Chem. Soc. B
1968, 550.