Synthesis of spiro-pyridopyridine analogues by Grubbs' catalyst mediated alkene and enyne metathesis reaction

Article abstract of DOI:10.1039/b603125k

A practical synthesis of spiro-naphthyridinone derivatives is described by the combination of the Claisen rearrangement and ring-closing metathesis/ring-closing enyne metathesis process. The RCM or RCEM proceeded smoothly in the presence of Grubbs' first

Full text of DOI:10.1039/b603125k

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Synthesis of spiro-pyridopyridine analogues by Grubbs’ catalyst mediated
alkene and enyne metathesis reaction†
K. C. Majumdar,* R. Islam, H. Rahaman and B. Roy
Received 1st March 2006, Accepted 19th April 2006
First published as an Advance Article on the web 10th May 2006
DOI: 10.1039/b603125k
A practical synthesis of spiro-naphthyridinone derivatives is described by the combination of the
Claisen rearrangement and ring-closing metathesis/ring-closing enyne metathesis process. The RCM or
RCEM proceeded smoothly in the presence of Grubbs’ first generation catalyst at room temperature
under a nitrogen atmosphere.
Of the six isomeric pyridopyridines, 1,8-naphthyridine derivatives
have received considerable attention in the last 15 years. This
class of compounds has attracted considerable attention primarily
due to the presence of a 1,8-naphthyridine skeleton in many
compounds which have been isolated from natural substances and
exhibit various biological activities. Substituted naphthyridines
are used for combating exo- and endo-parasites in agriculture
and in cattle breeding, as preservatives and ingredients of cutting
fluids, and also as ligands in analytical chemistry.1 Compounds in
these classes exhibit fungicidal activity against phytopathogenic
fungi and some of these patent drugs are used for the treat-
ment of memory loss, aging and Alzheimer’s disease and also
as antiallergic agents.2 In particular, naphthyridines and spiro-
naphthyridinones are useful for suppressing the immune response
and in the treatment of autoimmune and other immune disorders.3
Compound 1a had an ED50 of 0.13 mg topically in the arachidonic
acid mouse ear test, a measure of its utility in the treatment
of hyperproliferative skin diseases.4 Compound 1b was used to
treat arachidonic acid induced edema by 82% in comparison to a
non-treated control. An ointment was prepared for these diseases,
which contained compound 1 with benzyl alcohol, mineral oil and
white petroleum base.5
carboxylate, c-valerolactone, and KOCMe3 was heated at 110 ◦C
for 5 h to afford substituted hydroxynaphthyridinone. Finally the
hydroxynaphthyridin-2(1H)-one was heated with Eaton’s reagent
to give the corresponding spiro-naphthyridinone 1.4
Our strategy is based on the tandem Claisen rearrangement and
RCM/RCEM protocol. Recently ring closing metathesis6 and ring
closing enyne metathesis7 has been proved to be highly effective
for the synthesis of different ring compounds from acyclic diene or
dienyne precursors. RCM is very high yielding, easier to perform
and tolerant of a wide variety of functional groups. In the RCM
process, the ring-closed products lack the number of carbon atoms
but the RCEM has its advantage in that it is an atom economical
reaction. This success hinges on the development of a well-defined
catalyst such as Grubbs’ catalyst A8 and its functional group
tolerance. Hence it appeared to us that the combination of a
Claisen rearrangement and RCM/RCEM could be a synthetic
strategy to prepare various spiro-naphthyridinone analogues.
Herein we wish to report our results. The retro-synthetic analysis
of the title compound 1 is summarized in Scheme 1.
Compounds 2, 3, 4 and 5 were prepared according to our
previously published procedure.9 The O,C-dialkylated products
5 in refluxing chlorobenzene for 3 h afforded the corresponding
C,C-dialkylated product 6 in 90% yield (Scheme 2). Also a simple
alkylation of compound 2 with allyl bromide (2 equivalents) in
refluxing dry acetone in the presence of anhydrous K2CO3 for
about 40 h afforded C,C-diallylated product (20–22%) (6) along
with the O,C-diallylated product (5) (Scheme 3).
Initially we have focused our attention on the synthesis of spiro-
annulated heterocyclic products via the ring closing metathesis
process. To test this premise, a dichloromethane solution of the
compound 6a and Grubbs’ catalysts A (10 mol %) was stirred at
room temperature under a nitrogen atmosphere for 7 h. Usual
workup of the reaction mixture afforded the corresponding spiro-
derivative 7a in 92% yield (Scheme 4). Similarly 7b was obtained
from 6b in 90% yield.
The synthetic procedure for the patent compound 1 is quite
complicated. They were synthesized from a complex starting ma-
terial, ethyl 2-[(3,4-dichlorophenyl)amino]-3-pyridinecarboxylate.
A mixture of ethyl 2-[(3,4-dichlorophenyl)amino]-3-pyridine-
Department of Chemistry, University of Kalyani, Kalyani, 741235, West
Bengal, India. E-mail: kcm_ku@yahoo.co.in
† Electronic supplementary information (ESI) available: Mass spectrum of
7a and 1H NMR of 7a and 10a. See DOI: 10.1039/b603125k
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The spiroheterocycles 7a,b were characterized from their ele-
mental analyses and spectroscopic data. Compound 7a showed a
two-proton singlet at d5.64 indicating the presence of two olefinic
protons and two non-equivalent doublets at d3.08–3.12 (two
protons) and d3.16–3.20 (two protons) indicating the methylene
protons in the five-membered ring. Encouraged by the results of
the RCM of dienes 6a,b, we undertook a study of the synthesis of
substituted spiro-derivatives via the ring closing enyne metathesis.
Synthesis of the RCEM precursors is depicted in Scheme 5.
Straightforward alkylation of compound 4 with 2 equivalents of
propargyl bromide/1-aryloxy-4-chlorobut-2-yne 8a–d in reflux-
ing acetone for 7–8 h afforded the corresponding C,C-dienyne
derivatives 9a–d in 30–40% yield along with O,C-dialkylated
products. The desired dienynes 9a–d were easily separated by
column chromatography over silica gel using 9 : 1 petroleum ether–
ethyl acetate as eluant.
The analogous substituted spiro-naphthyridinone derivatives
10a–d were prepared by conventional RCEM procedure. When
a dichloromethane solution of 9a and the Grubbs’ catalyst A was
stirred at room temperature for 4 h under a nitrogen atmosphere,
the desired vinyl substituted 10a was obtained in 85% yield.
Scheme 1
Scheme 2
Scheme 3 Reagents and reaction conditions: (i) Dry acetone, K2CO3, allyl bromide (2 equiv.), reflux, 40 h.
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Scheme 4
Scheme 5
Scheme 6
Similarly other spiroheterocycles 10b–d were obtained in 92–96%
yield from 9b–d (Scheme 6).
Thus we have demonstrated a synthetic strategy for the prepara-
tion of spiro-naphthyridinone derivatives via the RCM and RCEM
protocol. The biological activity of the compound 1 is well known
and recently, it has been used as a drug for hyperproliferative
skin diseases. Hence its analogous derivatives (substituted or
unsubstituted) may be potentially bioactive compounds. Our
RCM/RCEM protocol for the synthesis of target molecules is
facile and the yield of the products is excellent. Therefore, we
believe that our procedure is superior to the previously reported
one.
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gel. Elution of the column with petroleum ether–ethyl acetate (9 :
1) furnished compounds 9a–d.
Experimental
Melting points were determined in an open capillary and are
uncorrected. IR spectra were recorded on a Perkin-Elmer L 120-
000A spectrometer (mmax in cm−1) on KBr disks. UV absorption
spectra were recorded in EtOH on a Shimadzu UV-2401PC spec-
trophotometer (kmax in nm). 1H NMR (400 MHz) and 13C NMR
(125.7 MHz) spectra were recorded on AVANCE-400 and Bruker
DPX-500 spectrometers in CDCl3 (chemical shifts in d) with TMS
as internal standard. Elemental analyses and mass spectra were
recorded on a Leco 932 CHNS analyzer and on a JEOL JMS-
600 instrument respectively. 1H NMR and 13C NMR spectra were
recorded at the Indian Institute of Chemical Biology, Kolkata,
Bose Institute, Kolkata and Chembiotek Research International,
Kolkata. Silica gel [(60–120 mesh), Spectrochem, India] was used
for chromatographic separation. Silica gel G [E-Merck (India)]
was used for TLC. Petroleum ether refers to the fraction boiling
between 60–80 ◦C. The 1-aryloxy-4-chlorobut-2-ynes 8a–d were
prepared according to the published procedure.10
Compound 9a. Yield: 30%; white crystalline solid; mp 135–
137 ◦C; IR (KBr) mmax: 3285, 3267, 2921, 1702, 1668, 1586,
1
1435, 1358 cm−1; UV (EtOH) kmax: 333, 263, 227 nm; H NMR
(400 MHz, CDCl3): dH 1.91–1.92 (t, J = 2.3 Hz, 1H), 2.76–2.78 (d,
J = 7.3 Hz, 2H, –CH2), 2.93 (d, J = 1.9 Hz, 2H, –CH2), 5.05–5.08
=
=
(d, J = 10.1 Hz, 1H, CH2), 5.12–5.17 (d, J = 16.6 Hz, 1H, CH2),
=
5.60–5.66 (m, 1H, –CH ), 7.09–7.13 (dd, J = 4.7 Hz, 7.5 Hz, 1H,
ArH), 7.21–7.25 (m, 2H, ArH), 7.45–7.48 (t, J = 7.2 Hz, 1H, ArH),
7.52–7.56 (t, J = 7.2 Hz, 2H, ArH), 8.31–8.33 (dd, J = 1.6 Hz,
7.6 Hz, 1H, ArH), 8.43–8.45 (dd, J = 1.6 Hz, 4.5 Hz, 1H, ArH);
MS: m/z = 316 (M+); Anal. Calcd for C20H16N2O2: C, 75.95; H,
5.06; N, 8.86%. Found: C, 75.76; H, 4.85; N, 9.09%.
Compound 9b. Yield: 32%; white crystalline solid; mp 94–
◦
96 C; IR (KBr) mmax: 2922, 1698, 1668, 1586 cm−1; UV (EtOH)
1
kmax: 335, 264, 225 nm; H NMR (400 MHz, CDCl3): dH 2.19 (s,
3H, –CH3), 2.73–2.75 (d, J = 7.3 Hz, 2H, –CH2), 2.95 (s, 2H,
–CH2), 4.37–4.41 (d, J = 15.6 Hz, 1H), 4.45–4.49 (d, J = 15.6 Hz,
General procedure for the preparation of compounds 6a,b
=
1H), 5.03–5.05 (d, J = 10 Hz, 1H, CH2), 5.10–5.14 (d, J = 17 Hz,
=
=
1H, CH2), 5.55–5.63 (m, 1H, CH–), 6.60–6.62 (d, J = 8.4 Hz,
2H, ArH), 6.86–6.88 (d, J = 8.2 Hz, 2H, ArH), 7.04–7.07 (m, 3H,
ArH), 7.42–7.48 (m, 3H, ArH), 8.23–8.25 (dd, J = 1.6 Hz, 7.6 Hz,
1H, ArH), 8.38–8.40 (dd, J = 1.6 Hz, 4.5 Hz, 1H, ArH); MS: m/z =
436 (M+); Anal. Calcd for C28H24N2O3: C, 77.06; H, 5.50; N, 6.42%.
Found: C, 77.26; H, 5.69; N, 6.20%.
Compounds 5a,b (300 mg) were refluxed in chlorobenzene (4 ml)
for 3 h. The reaction mixture was then cooled and directly sub-
jected to column chromatography over silica gel. Chlorobenzene
was eluted out with petroleum ether. When the column was eluted
with 10% ethyl acetate–petroleum ether, compounds 6a,b were
obtained in 90–93% yield.
Compound 9c. Yield: 38%; white crystalline solid; mp 90–
Compound 6a. Yield: 90%; white crystalline solid; mp 108–
110 ◦C; IR (KBr) mmax: 2923, 1698, 1668, 1585 cm−1; UV (EtOH)
kmax: 333, 262, 224 nm; 1H NMR (400 MHz, CDCl3): dH 2.82–2.83
◦
92 C; IR (KBr) mmax: 2921, 1698, 1668, 1585 cm−1; UV (EtOH)
1
kmax: 335, 264, 223 nm; H NMR (400 MHz, CDCl3): dH 2.71–
2.73 (d, J = 7.3 Hz, 2H, –CH2), 2.96 (s, 2H, –CH2), 4.39–4.43 (d,
=
(d, J = 6.4 Hz, 4H, –CH2–), 5.01–5.03 (d, J = 9.6 Hz, 2H, CH2),
J = 15.8 Hz, 1H), 4.50–4.54 (d, J = 15.8 Hz, 1H), 5.03–5.05 (d,
=
=
5.09–5.14 (d, J = 17.2 Hz, 2H, CH2), 5.59–5.70 (m, 2H, –CH ),
7.05–7.23 (m, 3H, ArH), 7.42–7.45 (t, J = 7.6 Hz, 1H, ArH), 7.49–
7.52 (t, J = 7.6 Hz, 2H, ArH), 8.25–8.27 (dd, J = 1.6 Hz, 7.6 Hz,
1H, ArH), 8.38–8.40 (dd, J = 1.6 Hz, 4.8 Hz, 1H, ArH), MS: m/z =
318 (M+); Anal. Calcd for C20H18N2O2: C, 75.47; H, 5.66; N, 8.80%.
Found: C, 75.68; H, 5.84; N, 8.66%.
=
=
J = 10.1 Hz, 1H, CH2), 5.10–5.14 (d, J = 16.8 Hz, 1H, CH2),
=
5.55–5.62 (m, 1H, CH–), 6.63–6.65 (d, J = 8.8 Hz, 2H, ArH),
6.98–7.01 (d, J = 8.8 Hz, 2H, ArH), 7.05–7.09 (m, 3H, ArH),
7.44–7.52 (m, 3H, ArH), 8.29–8.32 (dd, J = 1.2 Hz, 7.4 Hz, 1H,
ArH), 8.44–8.45 (d, J = 2.9 Hz, 1H, ArH) MS: m/z = 458, 456
(M+); Anal. Calcd for C27H21ClN2O3: C, 70.97; H, 4.60; N, 6.13%.
Found: C, 70.73; H, 4.76; N, 6.34%.
Compound 6b. Yield: 93%; white crystalline solid; mp 108–
110 ◦C; IR (KBr) mmax: 2923, 1698, 1668, 1585 cm−1; UV (EtOH)
kmax: 333, 262, 224 nm; 1H NMR (400 MHz, CDCl3): dH 2.83–2.84
Compound 9d. Yield: 40%; colorless solid; mp 101–103 ◦C; IR
(KBr) mmax: 2921, 1696, 1668, 1584 cm−1; UV (EtOH) kmax: 333, 264,
221 nm; 1H NMR (400 MHz, CDCl3): dH 2.71–2.73 (d, J = 7.3 Hz,
2H, –CH2), 2.94 (s, 2H, –CH2), 4.38–4.42 (d, J = 15.8 Hz, 1H),
4.52–4.56 (d, J = 15.8 Hz, 1H), 5.01–5.03 (d, J = 10.1 Hz, 1H,
=
(d, J = 6.4 Hz, 4H, –CH2–), 5.01–5.03 (d, J = 9.6 Hz, 2H, CH2),
=
=
5.11–5.15 (d, J = 17.2 Hz, 2H, CH2), 5.59–5.71 (m, 2H, –CH ),
7.07–7.25 (m, 2H, ArH), 7.43–7.47 (t, J = 7.6 Hz, 1H, ArH), 7.49–
7.52 (t, J = 7.6 Hz, 2H, ArH), 8.26–8.28 (dd, J = 1.6 Hz, 7.6 Hz,
1H, ArH), 8.38–8.40 (dd, J = 1.6 Hz, 4.8 Hz, 1H, ArH), MS: m/z =
354, 352 (M+); Anal. Calcd for C20H17ClN2O2: C, 68.08; H, 4.82;
N, 7.94%. Found: C, 68.30; H, 4.96; N, 8.11%.
=
=
CH2), 5.10–5.14 (d, J = 16.8 Hz, 1H, CH2), 5.55–5.63 (m, 1H,
=
–CH ), 6.66–6.68 (d, J = 8.8 Hz, 2H, ArH), 6.98–7.01 (d, J =
8.8 Hz, 2H, ArH), 7.05–7.11 (m, 3H, ArH), 7.44–7.57 (m, 2H,
ArH), 8.24–8.26 (dd, J = 1.2 Hz, 7.4 Hz, 1H, ArH), 8.41–8.43
(d, J = 2.9 Hz, 1H, ArH); MS: m/z = 494, 492, 490 (M+); Anal.
Calcd for C27H20Cl2N2O3: C, 65.98; H, 4.07; N, 5.70%. Found: C,
66.18; H, 4.28; N, 5.93%.
General procedure for the preparation of compounds 9a–d
A mixture of 3-allyl-4-hydroxy-1-phenyl-1,8-naphthyridin-2(1H)-
one (4) (2 mmol), 2 equivalents of propargyl bromide/1-aryloxy-
4-chlorobut-2-yne 8a–d and anhydrous K2CO3 (2 g) was refluxed
in dry acetone (60 ml) for 7–8 h. The reaction mixture was cooled
and filtered. Removal of solvent from the filtrate gave a gummy
mass. This was subjected to column chromatography over silica
Typical procedure for ring closing metathesis reaction for the
preparation of compounds 7 and 10
To a solution of substrate 6a (50 mg, 0.158 mmol) in dry degassed
CH2Cl2 (8 ml) under N2 was added catalyst A (10 mol%, 13 mg)
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and the reaction was stirred at room temperature for 4 h. After the
removal of the solvent, the residue was purified by flash column
chromatography on silica gel (petroleum ether–ethyl acetate, 4 :
1) to give 7a in 92% yield. The diene 6b and dienynes 9a–d were
treated in a similar manner to give the corresponding cyclized
products 7b and 10a–d in excellent yield.
225 nm; 1H NMR (400 MHz, CDCl3): dH 3.21–3.39 (m, 4H, –CH2),
=
=
4.68 (s, 2H, –OCH2), 5.15 (s, 1H, CH2), 5.32 (s, 1H, CH2), 5.70
=
(s, 1H, CH–), 6.83–6.85 (d, J = 8.8 Hz, 2H, ArH), 7.11–7.14 (dd,
J = 4.8 Hz, 7.5 Hz, 1H, ArH), 7.20–7.25 (m, 4H, ArH), 7.44–7.47
(t, J = 7.3 Hz, 1H, ArH), 7.52–7.56 (t, J = 7.3 Hz, 2H, ArH),
8.29–8.32 (dd, J = 1.5 Hz, 7.6 Hz, 1H, ArH), 8.44–8.45 (dd, J =
1.5 Hz, 4.5 Hz, 1H, ArH); MS: m/z = 458, 456 (M+); Anal. Calcd
for C27H21ClN2O3: C, 70.97; H, 4.60; N, 6.13%. Found: C, 71.15;
H, 4.81; N, 5.89%.
Compound 7a. Yield: 92%; white solid; mp 230–232 ◦C; IR
(KBr) mmax: 2925, 1708, 1671, 1584 cm−1; UV (EtOH) kmax: 326,
261, 219 nm; 1H NMR (400 MHz, CDCl3): dH 3.08–3.12 (d, J =
15.5 Hz, 2H, –CH2), 3.16–3.20 (d, J = 15.5 Hz, 2H, –CH2), 5.64
Compound 10d. Yield: 93%; white crystalline solid; mp 162–
164 ◦C; IR (KBr) mmax: 2921, 1713, 1683, 1585 cm−1; UV (EtOH)
kmax: 322, 261, 221 nm; 1H NMR (400 MHz, CDCl3): dH 3.21–3.38
=
(s, 2H, –CH CH–), 7.09–7.12 (m, 1H, ArH), 7.21–7.24 (m, 2H,
ArH), 7.43–7.47 (t, J = 7.3 Hz, 1H, ArH), 7.51–7.55 (t, J = 7.3 Hz,
2H, ArH), 8.28–8.31 (dd, J = 1.3 Hz, 7.6 Hz, 1H, ArH), 8.43–8.44
(dd, J = 1.3 Hz, 4.3 Hz, 1H, ArH); MS: m/z = 290 (M+); Anal.
Calcd for C18H14N2O2: C, 74.48; H, 4.82; N, 9.65%. Found: C,
74.67; H, 5.05; N, 9.82%.
=
(m, 4H, –CH2), 4.68 (s, 2H, –OCH2), 5.14 (s, 1H, CH2), 5.30 (s,
=
=
1H, CH2), 5.70 (s, 1H, CH–), 6.82–6.84 (d, J = 8.8 Hz, 2H,
ArH), 7.10–7.13 (dd, J = 4.8 Hz, 7.5 Hz, 1H, ArH), 7.22–7.27 (m,
4H, ArH), 7.40–7.46 (t, J = 7.3 Hz, 1H, ArH), 7.51–7.55 (t, J =
7.3 Hz, 2H, ArH), 8.29–8.31 (dd, J = 1.5 Hz, 7.6 Hz, 1H, ArH),
8.44–8.46 (dd, J = 1.5 Hz, 4.5 Hz, 1H, ArH); MS: m/z = 494,
492, 490 (M+); Anal. Calcd for C27H20Cl2N2O3: C, 65.98; H, 4.07;
N, 5.70%. Found: C, 65.75; H, 4.25; N, 5.91%.
Compound 7b. Yield: 90%; white solid; mp 221–223 ◦C; IR
(KBr) mmax: 2923, 1706, 1674, 1583 cm−1; UV (EtOH) kmax: 325,
261, 217 nm; 1H NMR (400 MHz, CDCl3): dH 3.08–3.12 (d, J =
15.4 Hz, 2H, –CH2), 3.15–3.19 (d, J = 15.5 Hz, 2H, –CH2), 5.65
=
(s, 2H, –CH CH–), 7.12–7.15 (m, 2H, ArH), 7.23 (s, 1H, ArH),
7.42–7.48 (m, 2H, ArH), 8.29–8.31 (dd, J = 1.5 Hz, 7.6 Hz, 1H,
ArH), 8.43–8.44 (dd, J = 1.5 Hz, 4.5 Hz, 1H, ArH); MS: m/z =
326, 324 (M+); Anal. Calcd for C18H13ClN2O2: C, 66.56; H, 4.00;
N, 8.62%. Found: C, 66.75; H, 4.21; N, 8.87%.
Acknowledgements
This work was financially supported by the CSIR (New Delhi). Mr
R. I. is grateful to the CSIR (New Delhi) for providing the Senior
Research Fellowship and Mr H. R. is grateful to the University of
Kalyani for providing a Senior Research Fellowship.
Compund 10a. Yield: 85%; white crystalline solid; mp 182–
184 ◦C; IR (KBr) mmax: 2918, 1709, 1675, 1583 cm−1; UV (EtOH)
kmax: 316, 263, 223 nm; 1H NMR (400 MHz, CDCl3): dH 3.14–3.28
References
=
=
(m, 4H, –CH2), 5.04–5.12 (m, 2H, CH2), 5.60 (s, 1H, CH),
=
6.48–6.55 (dd, J = 10.7 Hz, 17.4 Hz, 1H, CH–), 7.10–7.13 (dd,
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J = 4.8 Hz, 7.4 Hz, 1H, ArH), 7.21–7.24 (m, 2H, ArH), 7.44–7.47
(t, J = 7.3 Hz, 1H, ArH), 7.51–7.55 (t, J = 7.3 Hz, 2H, ArH),
8.28–8.31 (dd, J = 1.4 Hz, 7.6 Hz, 1H, ArH), 8.43–8.45 (dd, J =
1.4 Hz, 4.4 Hz, 1H, ArH); 13C NMR (CDCl3, 125.7 MHz): 40.6,
42.7, 62.9, 115.4, 115.7, 119.5, 126.3, 128.9, 129.2, 129.9, 132.5,
137.2, 137.4, 139.8, 154.6, 155.5, 174.0, 194.5, MS: m/z = 316
(M+); Anal. Calcd for C20H16N2O2: C, 75.95; H, 5.06; N, 8.86%.
Found: C, 76.16; H, 5.26; N, 8.62%.
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Dechert and F. Meyer, Organometallics, 2005, 24, 4049; (j) R. Pedrosa,
C. Andres, A. Gutierrez-Loriente and J. Nieto, Eur. J. Org. Chem.,
2005, 2449; (k) C. Bolm and H. Viller, Synthesis, 2005, 1345; (l) B. S.
Lee, S. K. Namgoong and S. Lee, Tetrahedron Lett., 2005, 46, 4501;
(m) B. Wels, J. A. W. Kruijtzer, K. Garner, W. A. J. Nijenhuis, W. H.
Gispen, R. A. H. Adan and R. M. Liskamp, Bioorg. Med. Chem.,
2005, 13, 4221; (n) S. Park, M. Kim and D. Lee, J. Am. Chem. Soc.,
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2965.
◦
Compound 10b. Yield: 92%; colorless solid; mp 152–154 C;
IR (KBr) mmax: 2921, 1714, 1678, 1582 cm−1; UV (EtOH) kmax: 356,
265, 224 nm; 1H NMR (400 MHz, CDCl3): dH 2.27 (s, 3H, –CH3),
3.20–3.39 (m, 4H, –CH2), 4.68 (s, 2H, –OCH2), 5.13 (s, 1H, CH),
=
=
=
5.34 (s, 1H, CH), 5.72 (s, 1H, CH), 6.80–6.83 (d, J = 8.4 Hz,
2H, ArH), 7.05–7.07 (d, J = 8.2 Hz, 2H, ArH), 7.11–7.14 (dd,
J = 4.8 Hz, 7.4 Hz, 1H, ArH), 7.22–7.25 (m, 2H, ArH), 7.44–7.48
(t, J = 7.2 Hz, 1H, ArH), 7.52–7.55 (t, J = 7.2 Hz, 2H, ArH), 8.29–
8.31 (dd, J = 1.4 Hz, 7.5 Hz, 1H, ArH), 8.44–8.45 (dd, J = 1.4 Hz,
4.4 Hz, 1H, ArH);13C NMR (CDCl3, 125.7 MHz): 20.8, 42.4, 43.3,
62.3, 69.4, 115.1, 115.2, 115.5, 119.6, 123.3, 129.0, 129.2, 130.0,
130.2, 130.6, 137.2, 137.4, 137.8, 138.6, 154.6, 155.5, 156.9, 173.9,
194.4; MS: m/z = 436 (M+); Anal. Calcd for C28H24N2O3: C, 77.06;
H, 5.50; N, 6.42%. Found: C, 77.31; H, 5.71; N, 6.28%.
7 (a) S. T. Diver and R. T. Giessert, Chem. Rev., 2004, 104, 1317;
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737; (c) S.-H. Kim, N. Bowden and R. H. Grubbs, J. Am. Chem. Soc.,
◦
Compound 10c. Yield: 96%; white solid; mp 146–148 C; IR
(KBr) mmax: 2917, 1715, 1680, 1582 cm−1; UV (EtOH) kmax: 320, 261,
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