Regioselective aryl radical cyclization: Access to pyrimidine-annelated Spiro heterocycles through 5-exo ring closure

Article abstract of DOI:10.1055/s-2004-829133

Aryl radical cyclization of a range of 6-(2^′- bromophenoxymethyl)-1,3-dimethyluracils 4a-g was carried out with tributyltin chloride and sodium cyanoborohydride in the presence of AIBN for four hours to give exclusively the '5-exo' cyclization products, 1,3-dimethylspiro[pyrimidine- 6,3′-2′,3′-tetrahydrobenzofuran]-2,4-diones 5a-g in 92-95% yield. The starting materials were in turn prepared in 90-92% yield by refluxing 6-chloro methyl-1,3-dimethyl uracil with various 2-bromophenols or 2-bromonaphthol in acetone in the presence of anhydrous potassium carbonate for eight hours.

Full text of DOI:10.1055/s-2004-829133

1864
PAPER
Regioselective Aryl Radical Cyclization: Access to Pyrimidine-Annelated
Spiro Heterocycles Through 5-exo Ring Closure
Regioselective
A
ry
.
l
Radical Cy
C
clization . Majumdar,* P. P. Mukhopadhyay
Department of Chemistry, University of Kalyani, Kalyani 741 235, West Bengal, India
Fax +91(33)25828282; E-mail: kcm@klyuniv.ernet.in
Received 20 February 2004; revised 26 April 2004
ical to an unfunctionalized double bond may be from
Abstract: Aryl radical cyclization of a range of 6-(2¢-bromophen-
oxymethyl)-1,3-dimethyluracils 4a–g was carried out with tributyl-
tin chloride and sodium cyanoborohydride in the presence of AIBN
for four hours to give exclusively the ‘5-exo’ cyclization products,
1,3-dimethylspiro[pyrimidine-6,3¢-2¢,3¢-tetrahydrobenzofuran]-
2,4-diones 5a–g in 92–95% yield. The starting materials were in
turn prepared in 90–92% yield by refluxing 6-chloro methyl-1,3-
dimethyl uracil with various 2-bromophenols or 2-bromonaphthol
in acetone in the presence of anhydrous potassium carbonate for
eight hours.
above and directly behind the p-orbitals,9b,c causing more
angle strain for the ‘5-exo’ transition state. The presence
of a carbonyl group may change this required trajectory in
accordance with Baldwin’s approach vector analysis,13 so
that the radical now approaches the double bond more
easily at the above stated direction. Many examples have
been reported of a useful ‘6-endo’ cyclization where the
carbonyl substituent12a,c or the nitrogen substituent14 is re-
garded as strongly activating towards ‘6-endo’ cycliza-
tion. Our present investigation on the regioselective
radical cyclization is solely controlled by the FMO inter-
actions.
Key words: heterocyclic compounds, spiro heterocycles, organotin
reagent, 6-chloromethyl-1,3-dimethyl uracil, radical cyclization, 5-
exo-trig
Recently we reported15 the ‘6-endo’ cyclization of 5-(2¢-
bromobenzyloxy)pyrimidine-2,4-dione with tri-n-butyl-
tin chloride and sodium cyanoborohydride in the presence
of azobisisobutyronitrile (AIBN). As part of our ongoing
work, we became interested in the synthesis of pyrimidine
derivatives due to their proven biological activity and me-
dicinal utility. Recently, a 6-substituted uracil derivative,
Introduction
Intramolecular radical cyclizations to an unsaturated dou-
ble bond are extremely useful for the construction of five-
and six-membered carbo- and heterocyclic rings.1 In par-
ticular, the intramolecular addition of aryl radicals to dou-
ble bonds is well documented in the literature2 for the
synthesis of spiro heterocycles.3 In contrast, for the addi-
tion to carbocycles there are relatively few reports dealing
with the intramolecular addition of aryl radicals to hetero-
cyclic rings.4–7 It was observed that the parent 5-hexenyl
radical cyclized preferentially to the cyclopentyl methyl
radical via ‘5-exo’ cyclization and not to the more stable
cyclohexyl radical via ‘6-endo’ cyclization.8 This is gen-
erally predicted by using the Beckwith9 transition state
model. Beckwith10 rationalized this regiochemical prefer-
ence by postulating that the bond formation between a
radical and a p-system stereoelectronically required an ap-
proach angle of about 110° between the free radical centre
and the olefinic plane. This transition state geometry is
less constrained in ‘5-exo’ ring closure, a fact later elabo-
rated by Baldwin.11 Recent theoretical calculations have
also supported the Beckwith transition state model.12b,c
The regiochemical outcome of a radical cyclization may
be changed by the presence of radical stabilizing groups to
the acceptor double bond.12 It was also suggested that this
effect may be partly due to a change in the required ap-
proach trajectory for radical additions to the substituted
acceptor double bond. The direction of approach of a rad-
1-(2-hydroxyethoxymethyl)-6-phenylthio
thymine
(HEPT)16–18 has attained considerable significance as a
specific inhibitor for HIV-1,19 a causative agent of AIDS.
Functionalization of uracils at C-5 and C-6 leads to bio-
logically interesting molecules but it is not a simple task,
requiring rather sophisticated and tedious reaction condi-
tions.20,21 We have recently reported the synthesis of a
number of pyrimidine-annelated heterocycles fused at the
C-5 and C-6 positions of uracil.15,22 Herein we report the
regioselective formation of spiro pyrimidine heterocycles.
Results and Discussion
We started our investigation by examining the cyclization
of several 6-(2¢-bromophenoxymethyl)-1,3-dimethyl-
uracils (4a–g) which were readily prepared in 90–92%
yields from various o-bromophenols or 2-bromonaphthol
3a–g and 6-chloromethyl-1,3-dimethylpyrimidine-2,4-di-
one (2) in eight hours in the presence of anhydrous K2CO3
(Scheme 1).
The ethers were treated with n-Bu3SnH–AIBN to induce
radical cyclization. Compound 4a, when heated with n-
Bu3SnCl in the presence of Na(CN)BH3 and small
amounts of AIBN in refluxing degassed benzene under ni-
trogen for four hours afforded exclusively 5a in excellent
yield (95%) (Scheme 2).
SYNTHESIS 2004, No. 11, pp 1864–1868
Advanced online publication: 05.07.2004
DOI: 10.1055/s-2004-829133; Art ID: Z04304SS
© Georg Thieme Verlag Stuttgart · New York
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Regioselective Aryl Radical Cyclization
1865
with carbon resonance at d = 42.77 and 78.90, respective-
ly. Methine protons (ArH) resonance at d = 6.77, 6.94 and
7.09 are related with protonated carbon resonance at d =
110.96, 123.98 and 132, respectively. Encouraged by this
result, other substrates 4b–g were similarly treated to give
spiro heterocycles 5b–g in 92–95% yield. Our attempt to
extend this reaction to 6-(2¢-bromoanilinomethyl)-1,3-
dimethyl uracil and 6-(2¢-bromo-N-methylanilinometh-
yl)-1,3-dimethyl uracil afforded a complex mixture of
products, which could not be separated.
The regioselective formation of 5-membered heterocyclic
ring can be explained by the application of the FMO the-
ory. Aryl radicals are high-energy species and hence are
nucleophilic in character. The presence of highly electron-
withdrawing carbonyl group confers considerable electro-
philic character to the C-6 position of the uracil moiety.
Thus in the case of nucleophilic radical 6, FMO theory
suggests that the mode of ring closure is largely deter-
mined by the interaction between the radical SOMO
(≡ HOMO) and the alkene LUMO of the acceptor (elec-
tron deficient centre) and accordingly more favorable
bond formation occurs between the radical centre (nucleo-
philic) and C6 of the uracil ring for ‘5-exo’ product 5a–g
(Scheme 3). The same explanation may be extended to
our earlier results15,22a for the formation of ‘6-endo’ prod-
ucts from uracil substrates.
Scheme 1 Reagents and conditions: i) (CH3)2SO4, aq NaOH, reflux,
1.5 h; ii) Acetone, K2CO3, reflux, 8 h.
Scheme
2
Reagents and conditions: AIBN, n-Bu3SnCl,
Na(CN)BH3, benzene, reflux under N2 atmosphere for 4 h.
1
The H NMR spectrum of the product 5a revealed one
proton doublet at d = 2.93 (J = 16.5 Hz) and another one
proton doublet at d = 3.07 (J = 16.5 Hz) due to COCH2 and
another OCH2 protons appear as two one proton doublet
each at d = 4.34 and 4.45 (J = 10 Hz). Final confirmation
for structure 5a came from its COSY, HETCOR and 13C
NMR spectrum. COSY spectrum of compound 5a shows
that COCH2 protons at d = 2.93 and 3.07 correlate with
each other and OCH2 protons at d = 4.34 and 4.45 corre-
late with each other. The 13C NMR chemical shifts of the
compound 5a are assigned by DEPT and HETCOR exper-
iments. DEPT shows eight protonated carbons, three CH3,
three >CH, and two >CH2 groups. Protonated carbon res-
onances are established by direct correlation with proton
resonance by HETCOR experiment (normal one bond C-
H coupling). Methyl protons (ArCH3) resonance at d =
2.32 is related with protonated carbon resonance at d =
21.06 whereas another methyl protons at d = 2.80 and 3.26
(NCH3) are related with protonated carbon resonance at
d = 28.19 and 31.08, respectively. Methylene protons res-
onance at d = 2.93 (CH2CO) and 4.34 (OCH2) are related
Scheme 3
Previously we reported15 the synthesis of 1H,3H,6H-
[2]benzopyrano[4,3-d]pyrimidine-2,4-diones where regio-
selective ‘6-endo’ cyclization had occurred whereas in
our present investigation we find that the regioselective
‘5-exo’ cyclization has taken place. As this reaction is ir-
Synthesis 2004, No. 11, 1864–1868 © Thieme Stuttgart · New York

1866
K. C. Majumdar, P. P. Mukhopadhyay
PAPER
6-(2¢-Bromo-2¢-methylphenoxymethyl)-1,3-dimethyl-1H-pyri-
midine-2,4-dione (4c)
Yield: 90%; white solid; mp 160–162 °C.
IR (KBr): 1452, 1660, 1709, 2920 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.28 (s, 3 H, ArCH3), 3.39 (s, 3 H,
NCH3), 3.56 (s, 3 H, NCH3), 4.70 (s, 2 H, OCH2), 5.94 (s, 1 H,
=CH), 6.95 (m, 1 H, ArH), 7.40 (m, 2 H, ArH).
reversible and hence kinetically controlled, the outcome
of these radical cyclization cannot be explained by the sta-
bility of the intermediate product radical 7. The result can
only be explained by FMO interactions. This is a simple
and facile method for the synthesis of spiroheterocycles.
Melting points were determined in an open capillary and are uncor-
rected. IR spectra were recorded on a Perkin-Elmer L 120-000A
spectrometer (nmax in cm–1) on KBr disks. UV absorption spectra
were recorded in EtOH on a Shimadzu UV-2401PC spectrophoto-
meter (lmax in nm). 1H NMR (300 MHz, 500 MHz) and 13C NMR
(75.5 MHz, 125.7 MHz) spectra were recorded on a Bruker DPX-
300 and Bruker DPX-500 spectrometer in CDCl3 (chemical shift in
d) with TMS as internal standard. Elemental analyses and mass
MS: m/z = 338, 340 [M+].
UV (EtOH): lmax = 231, 267 nm.
Anal. Calcd for C14H15N2O3Br: C, 49.57; H, 4.45; N, 8.25. Found:
C, 49.38; H, 4.67; N, 8.33.
6-(2¢-Bromo-5¢-methoxyphenoxymethyl)-1,3-dimethyl-1H-py-
rimidine-2,4-dione(4d)
Yield: 92%; white solid; mp 180–182 °C.
IR (KBr): 1442, 1657, 1696, 2928 cm–1.
1H NMR (500 MHz, CDCl3): d = 3.37 (s, 3 H, NCH3), 3.54 (s, 3 H,
NCH3), 3.78 (s, 3 H, OCH3), 4.79 (s, 2 H, OCH2), 5.93 (s, 1 H,
=CH), 6.82 (d, J = 8 Hz, 1 H, ArH), 6.87 (d, J = 8 Hz, 1 H, ArH),
7.13 (s, 1 H, ArH).
1
spectra were recorded on a JEOL JMS-600 instrument. H NMR
and 13C NMR spectra were recorded at the Indian Institute of Chem-
ical Biology, Kolkata and Bose Institute, Kolkata. Silica gel (60–
120 mesh, Spectrochem, India) was used for chromatographic sep-
aration. Silica gel G (E-Merck, India] was used for TLC. Petroleum
ether refers to the fraction boiling between 60 °C and 80 °C.
Preparation of 6-(2¢-Bromophenoxymethyl)pyrimidine-2,4-di-
ones (4a–g), General Procedure
MS: m/z = 354, 356 [M+].
A mixture of 6-chloromethyl-1,3-dimethyl uracil (2, 5 mmol), and
either 2-bromophenols 3a–f or 2-bromonaphthol (3g, 5 mmol) and
anhyd K2CO3 (5 g) was heated at reflux in anhyd acetone (125 mL)
in a water bath for 8 h. The reaction mixture was then cooled, fil-
tered and the solvent was removed. The residual mass was extracted
with CH2Cl2 (3 × 50 mL). The CH2Cl2 extract was washed with 10%
Na2CO3 solution (2 × 25 mL) to remove unreacted 6-chloromethyl-
1,3-dimethyl uracil and then with brine (3 × 50 mL) and dried
(Na2SO4). The residual mass after removal of the solvent (CH2Cl2)
was subjected to column chromatography over silica gel using pe-
troleum ether–EtOAc (4:1) as eluant to give compounds 4a–g
which were then recrystallized from CHCl3–petroleum ether.
UV (EtOH): lmax = 230, 267 nm.
Anal. Calcd for C14H15N2O4Br: C, 47.34; H, 4.25; N, 7.88. Found:
C, 47.48; H, 3.98; N, 8.05.
6-(2¢-Bromo-3¢,5¢-dimethylphenoxymethyl)-1,3-dimethyl-1H-
pyrimidine-2,4-dione (4e)
Yield: 92%; white solid; mp 170–172 °C.
IR (KBr): 1452, 1660, 1709, 2923 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.38 (s, 3 H, ArCH3), 2.39 (s, 3 H,
ArCH3), 3.39 (s, 3 H, NCH3), 3.56 (s, 3 H, NCH3), 4.68 (s, 2 H,
OCH2), 5.96 (s, 1 H, =CH), 7.28 (s, 1 H, ArH), 7.35 (s, 1 H, ArH).
MS: m/z = 352, 354 [M+].
6-(2¢-Bromo-5¢-methylphenoxymethyl)-1,3-dimethyl-1H-pyri-
midine-2,4-dione (4a)
Yield: 90%; white solid; mp 178–180 °C.
IR (KBr): 1444, 1655, 1698, 2922 cm–1.
UV (EtOH): lmax = 230, 266 nm.
Anal. Calcd for C15H17N2O3Br: C, 51.00; H, 4.85; N, 7.93. Found:
C, 51.13; H, 4.98; N, 8.15.
1H NMR (300 MHz, CDCl3): d = 2.29 (s, 3 H, ArCH3), 3.36 (s, 3 H,
NCH3), 3.53 (s, 3 H, NCH3), 4.83 (s, 2 H, OCH2), 5.97 (s, 1 H,
=CH), 6.80 (d, J = 8 Hz, 1 H, ArH), 7.06 (d, J = 8 Hz, 1 H, ArH),
7.40 (s, 1 H, ArH).
6-(2¢-Bromophenoxymethyl)-1,3-dimethyl-1H-pyrimidine-2,4-
dione (4f)
Yield: 90%; white solid; mp 165–167 °C.
IR (KBr): 1442, 1662, 1697, 2925 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.37 (s, 3 H, NCH3), 3.53 (s, 3 H,
NCH3), 4.87 (s, 2 H, OCH2), 5.99 (s, 1 H, =CH), 6.97 (m, 2 H, ArH),
7.57 (m, 2 H, ArH).
MS: m/z = 338, 340 [M+].
UV (EtOH): lmax = 230, 266 nm.
Anal. Calcd for C14H15N2O3Br: C, 49.57; H, 4.45; N, 8.25. Found:
C, 49.31; H, 4.69; N, 8.43.
MS: m/z = 324, 326 [M+].
6-(2¢-Bromo-4¢-methylphenoxymethyl)-1,3-dimethyl-1H-pyri-
midine-2,4-dione (4b)
Yield: 90%; white solid; mp 198–200 °C.
IR (KBr): 1440, 1661, 1709, 2923 cm–1.
UV (EtOH): lmax = 230, 265 nm.
Anal. Calcd for C13H13N2O3Br: C, 48.02; H, 4.02; N, 8.62. Found:
C, 47.76; H, 4.18; N, 8.90.
6-(2¢-Bromopheneoxymethyl)-1,3-dimethyl-1H-pyrimidine-2,4-
dione (4g)
Yield: 90%; white solid; mp 160–162 °C.
IR (KBr): 1449, 1663, 1709, 2955 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.57 (s, 3 H, ArCH3), 3.38 (s, 3 H,
NCH3), 3.61 (s, 3 H, NCH3), 4.78 (s, 2 H, OCH2), 5.96 (s, 1 H,
=CH), 6.94 (d, J = 8 Hz, 1 H, ArH), 7.42 (d, J = 8 Hz, 1 H, ArH),
7.78 (s, 1 H, ArH).
MS: m/z = 338, 340 [M+].
1H NMR (500 MHz, CDCl3): d = 3.41 (s, 3 H, NCH3), 3.64 (s, 3 H,
NCH3), 4.91 (s, 2 H, OCH2), 6.06 (s, 1 H, =CH), 7.55 (m, 4 H, ArH),
7.86 (m, 1 H, ArH), 7.96 (m, 1 H, ArH).
UV (EtOH): lmax = 229, 268 nm.
Anal. Calcd for C14H15N2O3Br: C, 49.57; H, 4.45; N, 8.25. Found:
C, 49.78; H, 4.26; N, 8.40.
MS: m/z = 374, 376 [M+].
UV (EtOH): lmax = 233, 273 nm.
Synthesis 2004, No. 11, 1864–1868 © Thieme Stuttgart · New York

PAPER
Regioselective Aryl Radical Cyclization
UV (EtOH): lmax = 231, 289 nm.
1867
Anal. Calcd for C17H15N2O3Br: C, 54.41; H, 4.02; N, 7.46. Found:
C, 54.58; H, 3.88; N, 7.25.
Anal. Calcd for C14H16N2O3: C, 64.60; H, 6.19; N, 10.76. Found: C,
64.86; H, 5.98; N, 10.53.
Preparation of 1,3-Dimethylspiro[pyrimidine-6,3¢-2¢,3¢-tetrahy-
drobenzofuran]-2,4-dione 5a–g; General Procedure
Compound 5d
The compounds 4a–g (0.5 mmol), n-Bu3SnCl (0.08 mL, 0.296
mmol), Na(CN)BH3 (250 mg, 3.98 mmol) and AIBN (15 mg) were
dissolved in degassed anhyd benzene (8 mL) and the mixture was
heated at reflux for 4 h under N2 atmosphere. Solvent was evaporat-
ed under reduced pressure and the residue was taken up in water (10
mL) and was extracted with CH2Cl2 (3 × 10 mL). The combined or-
ganic extract was washed with 1% aq NH4OH (2 × 10 mL) and
brine, and dried (Na2SO4). Evaporation of the solvent furnished the
residual mass, which was then stirred with sat. solution of KF for 24
h. It was then extracted with CH2Cl2 (3 × 10 mL) and was washed
several times with water and dried (Na2SO4). The residual mass af-
ter removal of the solvent (CH2Cl2), was subjected to column chro-
matography using petroleum ether–EtOAc (19:1) as eluant to give
cyclized products 5a–g which were then recrystallized from
CHCl3–petroleum ether.
Yield: 94%; white solid; mp 120–122 °C.
IR (KBr): 1493, 1670, 1709, 2944 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.83 (s, 3 H, NCH3), 2.96 (d, J =
16.5 Hz, 1 H, COCH), 3.08 (d, J = 16.5 Hz, 1 H, COCH), 3.25 (s, 3
H, NCH3), 3.78 (s, 3 H, OCH3), 4.36 (d, J = 10 Hz, 1 H, OCH), 4.45
(d, J = 10 Hz, 1 H, OCH), 6.69 (s, 1 H, ArH), 6.81 (d, J = 8 Hz, 1
H, ArH), 6.86 (d, J = 8 Hz, 1 H, ArH).
MS: m/z = 276 [M+].
UV (EtOH): lmax = 232, 305 nm.
Anal. Calcd for C14H16N2O4: C, 60.86; H, 5.83; N, 10.13. Found; C,
61.01; H, 5.95; N, 10.30.
Compound 5e
Yield: 92%; white solid; mp 162–164 °C.
IR (KBr): 1473, 1668, 1718, 2928 cm–1.
Compound 5a
Yield: 95%; white solid; mp 120–122 °C.
1H NMR (300 MHz, CDCl3): d = 2.29 (s, 3 H, ArCH3), 2.38 (s, 3 H,
ArCH3), 2.81 (s, 3 H, NCH3), 2.92 (d, J = 16.5 Hz, 1 H, COCH),
3.04 (d, J = 16.5 Hz, 1 H, COCH), 3.26 (s, 3 H, NCH3), 4.36 (d, J =
10 Hz, 1 H, OCH), 4.46 (d, J = 10 Hz, 1 H, OCH), 6.87 (s, 1 H,
ArH), 7.36 (s, 1 H, ArH).
IR (KBr): 1494, 1672, 1713, 2918 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.32 (s, 3 H, ArCH3), 2.80 (s, 3 H,
NCH3), 2.93 (d, J = 16.5 Hz, COCH, 1 H), 3.07 (d, J = 16.5 Hz, 1
H, COCH), 3.27 (s, 3 H, NCH3), 4.34 (d, J = 10 Hz, 1 H, OCH), 4.45
(d, J = 10 Hz, 1 H, OCH), 6.77 (d, J = 8 Hz, 1 H, ArH), 6.95 (s, 1
H, ArH), 7.09 (d, J = 8 Hz, 1 H, ArH).
MS: m/z = 274 [M+].
13C NMR (CDCl3, 75.5 MHz): d = 21.06 (CH3), 28.19 (NCH3),
31.08 (NCH3), 42.77 (COCH2), 64.56 (NC), 78.90 (OCH2), 110.97,
123.98, 125.87, 131.67, 132.00, 153.84 (ArC), 157.90, 167.32
(NCO).
UV (EtOH): lmax = 231, 297 nm.
Anal. Calcd for C15H18N2O3: C, 65.67; H, 6.61; N, 10.21. Found: C,
65.81; H, 6.35; N, 10.39.
MS: m/z = 260 [M+].
Compound 5f
Yield: 94%; white solid; mp 110–112 °C.
IR (KBr): 1480, 1671, 1723, 2956 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.79 (s, 3 H, NCH3), 2.97 (d, J =
16.5 Hz, 1 H, COCH), 3.08 (d, J = 16.5 Hz, 1 H, COCH), 3.26 (s, 3
H, NCH3), 4.37 (d, J = 10 Hz, 1 H, OCH), 4.47 (d, J = 10 Hz, 1 H,
OCH), 6.88 (m, 2 H, ArH), 6.16 (m, 2 H, ArH).
UV (EtOH): lmax = 230, 289 nm.
Anal. Calcd for C14H16N2O3: C, 64.60; H, 6.19; N, 10.76. Found: C,
64.81; H, 5.95; N, 10.59.
Compound 5b
Yield: 92%; white solid; mp 138–140 °C.
IR (KBr): 1464, 1660, 1710, 2952 cm–1.
MS: m/z = 246 [M+].
1H NMR (500 MHz, CDCl3): d = 2.42 (s, 3 H, ArCH3), 2.81 (s, 3 H,
NCH3), 2.96 (d, J = 16.5 Hz, 1 H, COCH), 3.07 (d, J = 16.5 Hz, 1
H, COCH), 3.26 (s, 3 H, NCH3), 4.48 (d, J = 10 Hz, 1 H, OCH), 4.57
(d, J = 10 Hz, 1 H, OCH), 6.90 (d, J = 8 Hz, 1 H, ArH), 6.99 (d, J =
8 Hz, 1 H, ArH), 7.38 (s, 1 H, ArH).
UV (EtOH): lmax = 231, 281 nm.
Anal. Calcd for C13H14N2O3: C, 63.40; H, 5.73; N, 11.37. Found: C,
63.56; H, 5.45; N, 11.50.
Compound 5g
MS: m/z = 260 [M+].
Yield: 95%; white solid; mp 168–170 °C.
IR (KBr): 1444, 1662, 1718, 2957 cm–1.
UV (EtOH): lmax = 230, 288 nm.
1H NMR (500 MHz, CDCl3): d = 2.81 (s, 3 H, NCH3), 3.00 (d, J =
16.5 Hz, 1 H, COCH), 3.20 (d, J = 16.5 Hz, 1 H, COCH), 3.29 (s, 3
H, NCH3), 4.59 (d, J = 10 Hz, 1 H, OCH), 4.68 (d, J = 10 Hz, 1 H,
OCH), 7.22 (m, 4 H, ArH), 7.85 (m, 2 H, ArH).
Anal. Calcd for C14H16N2O3: C, 64.60; H, 6.19; N, 10.76. Found: C,
64.38; H, 6.37; N, 10.56.
Compound 5c
13C NMR (125.7 MHz, CDCl3): d = 28.47 (NCH3), 31.40 (NCH3),
43.33 (COCH2), 65.91 (NC), 79.91 (OCH2), 118.91, 120.29,
121.28, 122.19, 122.71, 126.79, 127.90, 128.49, 135.75, 154.13
(ArC), 156.47, 167.58 (NCO).
Yield: 92%; white solid; mp 96–98 °C.
IR (KBr): 1471, 1668, 1717, 2954 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.21 (s, 3 H, ArCH3), 2.82 (s, 3 H,
NCH3), 2.94 (d, J = 16.5 Hz, 1 H, COCH), 3.05 (d, J = 16.5 Hz, 1
H, COCH), 3.25 (s, 3 H, NCH3), 4.39 (d, J = 10 Hz, 1 H, OCH), 4.48
(d, J = 10 Hz, 1 H, OCH), 6.91 (m, 3 H, ArH).
MS: m/z = 296 [M+)].
UV (EtOH): lmax = 241, 300 nm.
MS: m/z = 260 [M+].
Anal. Calcd for C17H16N2O3: C, 68.90; H, 5.44; N, 9.45. Found: C,
68.81; H, 5.65; N, 9.59.
Synthesis 2004, No. 11, 1864–1868 © Thieme Stuttgart · New York

1868
K. C. Majumdar, P. P. Mukhopadhyay
PAPER
(7) (a) Tsuge, O.; Hatta, T.; Tsuchiyama, H. Chem. Lett. 1998,
155. (b) Fiumana, A.; Jones, K. Tetrahedron Lett. 2000, 41,
4209. (c) Sundberg, R. J.; Cherney, R. J. J. Org. Chem.
1990, 55, 6028.
(8) (a) Beckwith, A. L. J.; Ingold, K. U. In Rearrangement in
Ground and Excited States, Vol. 1; de Mayo, P., Ed.;
Academic Press: New York, 1980, 161. (b) Beckwith, A. L.
J. Tetrahedron 1981, 37, 3073.
Acknowledgment
We thank the CSIR (New Delhi) for financial assistance. P. P. Muk-
hopadhyay is grateful to CSIR (New Delhi) for a Senior Research
Fellowship. We also thank the DST (New Delhi) for providing the
UV-VIS spectrophotometer and FT-IR spectrometer under DST-
FIST.
(9) (a) Beckwith, A. L. J.; Easton, C. J.; Lawrence, T.; Serelis,
A. K. Aust. J. Chem. 1983, 36, 545. (b) Beckwith, A. L. J.;
Schiesser, C. H. Tetrahedron Lett. 1985, 26, 373.
(c) Beckwith, A. L. J.; Schiesser, C. H. Tetrahedron 1985,
41, 3925. (d) Spellmeyer, D. C.; Houk, K. N. J. Org. Chem.
1987, 52, 959.
References
(1) (a) Giese, B. Radicals in Organic Synthesis: Formation of
Carbon-Carbon Bonds; Pergamon: New York, 1986.
(b) Curran, D. P. Synthesis 1988, 417. (c) Curran, D. P.
Synthesis 1988, 489. (d) Jasperse, C. P.; Curran, D. P.;
Fevig, T. L. Chem. Rev. 1991, 91, 1237. (e) Radicals in
Organic Synthesis, Vol. 1; Renaud, P.; Sibi, M., Eds.; Wiley-
VCH: Weinheim, 2001. (f) Radicals in Organic Synthesis,
Vol. 2; Renaud, P.; Sibi, M., Eds.; Wiley-VCH: Weinheim,
2001. (g) Majumdar, K. C.; Basu, P. K. Heterocycles 2002,
57, 2413. (h) Bowman, W. R.; Fletcher, A. J.; Potts, G. B. S.
J. Chem. Soc., Perkin Trans. 1 2002, 2747.
(2) (a) Togo, H.; Kikuchi, O. Tetrahedron Lett. 1988, 29, 4133.
(b) Hart, D. J.; Wu, K. Tetrahedron Lett. 1991, 32, 4099.
(c) Clark, A. J.; Jones, K. Tetrahedron 1992, 48, 6875.
(d) Glover, S. A.; Warkentin, J. J. Org. Chem. 1993, 58,
2115. (e) Jones, K.; Brunton, S. A.; Gosain, R. Tetrahedron
Lett. 1999, 40, 8935. (f) Majumdar, K. C.; Mukhopadhyay,
P. P. Synthesis 2003, 99.
(3) (a) Flanagan, S. R.; Harrowven, D. C.; Bradley, M.
Tetrahedron Lett. 2003, 44, 1795. (b) Escolano, C.; Jones,
K. Tetrahedron 2002, 58, 1453. (c) Zhang, W.; Pugh, G.
Tetrahedron 2003, 59, 3009. (d) Zhang, W.; Pugh, G.
Tetrahedron 2003, 59, 4237.
(4) (a) Da Mata, M. L. E. N.; Motherwell, W. B.; Ujjainwalla, F.
Tetrahedron Lett. 1997, 38, 141. (b) Harrowven, D. C.;
Hon, B. J. S.; Coulton, S. Tetrahedron Lett. 2001, 42, 9061.
(c) Bonfand, E.; Forslund, L.; Motherwell, W. B.; Vazquez,
S. Synlett 2000, 475.
(10) Struble, D. A.; Beckwith, A. L. J.; Gream, G. A.
Tetrahedron Lett. 1968, 9, 3701.
(11) Baldwin, J. E. J. Chem. Soc., Chem. Commun. 1976, 734.
(12) (a) Ahmad-Juhan, S. A.; Whiting, D. A. J. Chem. Soc.,
Perkin Trans. 1 1990, 418. (b) Beckwith, A. L. J.; Blair, I.
A.; Phillipou, G. Tetrahedron Lett. 1974, 15, 2251.
(c) Ponaras, A. A.; Zaim, O. Tetrahedron Lett. 1993, 34,
2879.
(13) Beckwith, A. L. J. J. Chem. Soc., Chem. Commun. 1976,
738.
(14) (a) Takano, S.; Suzuki, M.; Kijima, S.; Ogasawara, K.
Tetrahedron Lett. 1990, 31, 2315. (b) Ishibashi, H.; Kato, I.;
Takeda, Y.; Kogure, M.; Tamura, O. Chem. Commun. 2000,
1527. (c) Ishibashi, H.; Ohata, K.; Niihara, M.; Sato, T.;
Ikeda, M. J. Chem. Soc, Perkin Trans. 1 2000, 547.
(15) Majumdar, K. C.; Basu, P. K.; Mukhopadhyay, P. P.; Sarkar,
S.; Ghosh, S. K.; Biswas, P. Tetrahedron 2003, 59, 2151.
(16) Miyasaka, T.; Tanaka, H.; Baba, M.; Hayakawa, H.; Walker,
R. T.; Balzarini, J.; DeClercq, E. J. Med. Chem. 1989, 32,
2507.
(17) Baba, M.; Tanaka, H.; DeClercq, E.; Pauwels, R.; Balzarini,
J.; Schols, D.; Nakashima, H.; Perno, C. F.; Walker, R. T.;
Miyasaka, T. Biochem. Biophys. Res. Commun. 1989, 165,
1375.
(18) DeClercq, E. Med. Res. Rev. 1993, 13, 229.
(19) (a) Gallo, R. C. Sci. Am. 1986, 255, 78. (b) Gallo, R. C. Sci.
Am. 1987, 256, 38.
(20) Kundu, N. G.; Das, P. J. Chem. Soc., Chem. Commun. 1995,
99.
(21) Botta, M.; Saladino, R.; Lamba, D.; Nicoletti, R.
Tetrahedron 1993, 49, 6053.
(22) (a) Majumdar, K. C.; Mukhopadhyay, P. P. Synthesis 2003,
920. (b) Majumdar, K. C.; Das, U.; Jana, N. K. J. Org.
Chem. 1998, 63, 3550.
(5) (a) Shankaran, K.; Solan, C. P.; Snieckus, V. Tetrahedron
Lett. 1985, 26, 6001. (b) Solan, C. P.; Cuevas, J. C.;
Quesnelle, C.; Snieckus, V. Tetrahedron Lett. 1988, 29,
4685. (c) Zhang, W.; Pugh, G. Tetrahedron Lett. 1999, 40,
7591.
(6) (a) Du, W.; Curran, D. P. Org. Lett. 2003, 5, 1765.
(b) Harrowven, D. C.; Browne, R. Tetrahedron Lett. 1994,
35, 5301. (c) Harrowven, D. C.; Sutton, B. J.; Coulton, S.
Tetrahedron 2002, 58, 3387. (d) Harrowven, D. C.; Nunn,
M. I. T.; Blumire, N. J.; Fenwick, D. R. Tetrahedron 2001,
57, 4447.
Synthesis 2004, No. 11, 1864–1868 © Thieme Stuttgart · New York