Formation of the 1H-pyrrolo[3,4-c]pyridin-1-one skeleton via intramolecular diels-alder reaction of oxazoles

Article abstract of DOI:10.3987/COM-11-12197

The 1H-pyrrolo[3,4-c]pyridin-1-one derivatives (4a-c) were prepared through a route employing the intramolecular Diels-Alder reaction of the oxazole-olefins (3a-c). Conversion of the crotonamide (3a) into 4a was effectively promoted by the addition of Cu(OTf)₂ as a catalyst.

Full text of DOI:10.3987/COM-11-12197

HETEROCYCLES, Vol. 83, No. 6, 2011
1395
HETEROCYCLES, Vol. 83, No. 6, 2011, pp. 1395 - 1403. © The Japan Institute of Heterocyclic Chemistry
Received, 2nd March, 2011, Accepted, 30th March, 2011, Published online, 18th April, 2011
DOI: 10.3987/COM-11-12197
FORMATION
OF
THE
1H-PYRROLO[3,4-c]PYRIDIN-1-ONE
SKELETON VIA INTRAMOLECULAR DIELS–ALDER REACTION OF
OXAZOLES
a,
a
b
b
Masashi Ohba, * Kei Fukuyama, Yuko Izumi, and Masaki Inaki
a
Yokohama College of Pharmacy, Matano-cho, Totsuka-ku, Yokohama 245-0066,
Japan; E-mail: m.ohba@hamayaku.ac.jp
b
Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi,
Kanazawa 920-1192, Japan
Abstract – The 1H-pyrrolo[3,4-c]pyridin-1-one derivatives (4a–c) were prepared
through a route employing the intramolecular Diels–Alder reaction of the
oxazole–olefins (3a–c). Conversion of the crotonamide (3a) into 4a was
effectively promoted by the addition of Cu(OTf)2 as a catalyst.
The intramolecular Diels–Alder reaction of oxazoles with olefinic dienophiles has become a useful tool to
produce annulated pyridines,1 since the first reports by two groups in 1983.2 This procedure has been
applied to the preparation of several pyridine-containing natural products, such as eupolauramine,2a,3
normalindine,4 suaveolines,5 and two monoterpene alkaloids.6 In connection with our ongoing synthetic
studies on two naphthyridine alkaloids, jasminine (1)7,8 and jasminidine (2),7c the formation of the
1H-pyrrolo[3,4-c]pyridin-1-one derivatives (4a–c) via the intramolecular Diels–Alder reaction of the
oxazole–olefins (3a–c) was investigated.
R1
N
R1
H
N
Me
N
Me
N
O
Me
N
N
O
O
O
R2
R2
R
1
2
: R = CO2Me
: R = H
3a
–
c
4a–c
a
b
: R1 = PhCH2, R2 = Me
: R1 = PhCH2, R2 = H
c
: R1 = Ph2CH, R2 = H

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HETEROCYCLES, Vol. 83, No. 6, 2011
We first envisioned the 3-butenamide (7) as a very attractive precursor for the synthesis of 2 by exploiting
the intramolecular oxazole cycloaddition. However, the initial attempt to heat 7, derived from the
oxazole amine (6),4 in o-dichlorobenzene (o-DCB) at 150 °C failed to give the expected pyridine
derivative, probably due to the internal hydrogen bonding of the amide NH with the oxazole oxygen as
shown in 7A, which prevents access of the dienophile to the oxazole ring.9 Therefore, we planned to
employ the N-benzylamide (8) obtained from 54 through benzylation followed by deprotection of 9 and
condensation of the N-benzylamine (10) with 3-butenoic acid. Treatment of 8 in o-DCB containing
DBN (0.8 equiv)3 at 150 °C for 8 h provided (±)-4a possessing the 1H-pyrrolo[3,4-c]pyridin-1-one
skeleton in 62% yield, whereas the yield of the pyridine (4a) was quite low in the absence of DBN. The
formation of (±)-4a under the former conditions would be considered to take place via the isomerization
of 8 to the !,"-unsaturated isomer (11), as depicted in Scheme 2. These results led us to investigate the
intramolecular Diels–Alder reaction of the !,"-unsaturated amides (3a–c) tethered to an oxazole ring.
R
N
O
H
Me
N
Me
N
BocHN
H2N
Me
N
O
Me
N
O
CH2=CHCH2CO2H
DCC, CH2Cl2
ref. 4
O
O
O
N
7
: R = H
: R = PhCH2
5
6
7A
8
PhCH2Br
CH2=CHCH2CO2H
DEPC, Et3N
NaH, DMF
DMF
Ph
Ph
HN
Ph
Ph
Me
N
N
R2CH=CHCOCl
Me
N
BocN
CF3CO2H
CH2Cl2
Me
N
Me
N
O
N
!
O
additive
Na2CO3
benzene–H2O
O
O
O
R2
R2
9
10
3a,b
4a,b
Scheme 1
Ph
Ph
Ph
Ph
Me
N
Me
Me
N
N
N
Me
O
N
+
+
!
–H
H
–
O
O
O
8
DBN
O
N
N
N
Me
Me
Me
Me
11
(±)-4a
Scheme 2

HETEROCYCLES, Vol. 83, No. 6, 2011
1397
We initially examined the cycloaddition of the crotonamide (3a) derived from acylation of the amine (10)
with crotonoyl chloride using the Schotten–Baumann conditions (Table 1). When a 0.05 M solution of
3a in o-DCB was heated with DBN at 180 °C for 8 h under the conditions similar to those applied to 8,
the bicyclic pyridine (4a) was again obtained as a racemate in 83% yield (Entry 1). In the absence of
DBN, the reaction was slow, giving 4a in 40% yield after 24 h (Entry 2). The conversion of the
oxazole–olefins (12) into the cyclopenta[c]pyridines (13) is known to be effectively promoted by the
addition of a catalytic amount of Cu(OTf)2.10 The cycloaddition of 3a also smoothly proceeded at
120 °C in the presence of Cu(OTf)2 (10 mol %) to afford 4a in 94% yield (Entry 3). The enantiomeric
1
purity of the obtained 4a was estimated to be 98% ee by a H-NMR analysis using a chiral shift reagent.
Treatment of 4a with DBN in o-DCB at 180 °C for 8 h provided (±)-4a quantitatively, supporting the
mechanism shown in Scheme 2.
Me
Me
Me
O
R
Me
N
!
O
Cu(OTf)2
O
N
R
12
R = CO2Me (95%)
R = H (55%)
13
Scheme 3
a)
Table 1. Intramolecular Diels–Alder Reactions of the Oxazole–Olefins (3a–c) in o-DCB
Entry Substrate Additive (mol %) Temp. (°C) Time (h)
Product
Yield (%) % ee
1
2
3
4
5
6
7
8
9
3a
3a
3a
3a
3b
3b
3b
3c
3c
DBN (80)
––––
180
180
120
150
180
180
150
180
180
8
24
3
(±)-4a
4a
83
40
94
90
56
8
0
92
98
98
0
Cu(OTf)2 (10)
Cu(OTf)2 (2)
DBN (80)
––––
4a
0.75
4a
24
24
5
(±)-4b
4b
70
98
––
––
Cu(OTf)2 (2)
––––
4b
7
b)
b)
1.5
1.5
4c
25
25
Cu(OTf)2 (10)
4c
a)
All reactions were carried out in a 0.05 M solution.
Not determined.
b)

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HETEROCYCLES, Vol. 83, No. 6, 2011
The intramolecular Diels–Alder reaction of the acrylamide (3b) was next examined. On heating 3b,
prepared from 10 and acryloyl chloride, in o-DCB containing DBN at 180 °C for 24 h, the pyridine
[(±)-4b] was obtained in 56% yield (Entry 5), whereas the yield of 4b (70% ee) was very low without
DBN (Entry 6). The desired cycloaddition of 3b was only slightly promoted by the addition of
Cu(OTf)2, although 4b obtained in low yield revealed a high enantiomeric purity (Entry 7). The
differences in the reactivity between the crotonamide (3a) and the acrylamide (3b) are in general
agreement with our observation that the intramolecular oxazole cycloaddition of a terminal olefin is
difficult compared with that of an internal olefin possessing the ethyl group at the terminal position,
probably due to the rapid decomposition of the former at elevated temperature.11
Sammes and co-workers have described that a bulky protecting group, such as the diphenylmethyl and
trityl groups, accelerates the intramolecular Diels–Alder reaction between an olefin and a furan ring in
comparison with the benzyl group.12 The use of such steric buttresses could restrict conformational
freedom and have an effect on increasing the proximity of the diene and dienophile moieties. The
diphenylmethyl derivative (3c) was therefore prepared from the oxazole amine (6) through transimination
with benzophenone imine,13 followed by reduction of the imine (14) with sodium cyanoborohydride14 and
finally acylation of the resultant amine (15) with acryloyl chloride. However, the effect of the
diphenylmethyl group was slight. Thus, the pyridine (4c) was obtained in 25% yield, regardless of the
addition of Cu(OTf)2, on heating 3c at 180 °C for 1.5 h (Entries 8 and 9).
Ph
N
Ph
Ph
Ph
Ph
Ph
HN
Ph
Ph
Ph
Ph
NH
Me
N
Me
Me
Me
CH2=CHCOCl
N
O
N
NaBH3CN
!
6
MeOH–AcOH
Et3N, DMAP
benzene
O
O
O
O
N
N
N
14
15
3c
4c
Scheme 4
In conclusion, a new access to the 1H-pyrrolo[3,4-c]pyridin-1-one skeleton has now become possible via
the intramolecular Diels–Alder reaction of the oxazole–olefins (3a–c). The utility of the Cu(OTf)2
catalyst in this reaction was exemplified by the effective conversion of the crotonamide (3a) into the
pyridine (4a) accompanied by no racemization.
EXPERIMENTAL
General Notes. All melting points were determined on a Yamato MP-1 capillary melting point

HETEROCYCLES, Vol. 83, No. 6, 2011
1399
apparatus. Flash chromatography15 was carried out by using Merck silica gel 60 (No. 9385). The
organic solutions obtained after extraction were dried over anhydrous MgSO4 and concentrated under
reduced pressure. The ratios of solvents in mixtures are shown in v/v. Spectra reported herein were
recorded on a JEOL JMS-SX102A mass spectrometer, a Shimadzu FTIR-8400 IR spectrophotometer, or a
JEOL JNM-GSX-500 (1H 500 MHz) NMR spectrometer. Chemical shifts are reported in ! values
relative to internal Me4Si. Optical rotations were measured with a Horiba SEPA-300 polarimeter using a
1-dm sample tube.
(S)-N-[1-(5-Oxazolyl)ethyl]-3-butenamide (7). A mixture of 64 (726 mg, 6.5 mmol), 3-butenoic acid
(672 mg, 7.8 mmol), DCC (1.64 g, 7.9 mmol), and CH2Cl2 (30 mL) was stirred at rt for 70 min. The
precipitate was removed by filtration, and the filtrate was washed successively with saturated aqueous
NaHCO3 and brine, dried over anhydrous MgSO4, and concentrated in vacuo. Purification by flash
chromatography (AcOEt) provided 7 (1.01 g, 87%) as a colorless solid, which was recrystallized from
26
AcOEt–hexane (1 : 2) to give an analytical sample as colorless needles, mp 80–81 °C; ["]
–122° (c
D
1.00, MeOH); MS m/z: 180 (M+); IR (Nujol) #, cm-1: 3350 (NH), 1680 (amide CO); 1H-NMR (CDCl3) !:
1.51 (3H, d, J = 6.9 Hz, Me), 3.03 (2H, ddd, J = 7.2, 1.2, 1.2 Hz, COCH2), 5.24 (1H, ddt, J = 16.8, 1.2,
1.2 Hz) and 5.26 (1H, ddt, J = 10.2, 1.2, 1.2 Hz) (CH=CH2), 5.32 (1H, dq, J = 7, 6.9 Hz, CHMe), 5.81
(1H, br, NH), 5.92 (1H, ddt, J = 16.8, 10.2, 7.2 Hz, CH=CH2), 6.93 [1H, s, C(4)-H], 7.81 [1H, s, C(2)-H].
Anal. Calcd for C9H12N2O2: C, 59.99; H, 6.71; N, 15.55. Found: C, 59.85; H, 6.69; N, 15.48.
(S)-N-Benzyl-[1-(5-oxazolyl)ethyl]carbamic acid tert-butyl ester (9). A mixture of 54 (3.18 g, 15
mmol) and 60% NaH (647 mg, 16 mmol) in DMF (40 mL) was stirred at 0 °C in an atmosphere of N2,
and a solution of benzyl bromide (2.91 g, 17 mmol) in DMF (10 mL) was added dropwise over 15 min.
After stirring at rt for 1.5 h, the reaction mixture was concentrated in vacuo. The residue was partitioned
between ether and H2O, and the ethereal extracts were washed with brine, dried, and concentrated to leave
a colorless solid. Recrystallization of the solid from AcOEt–hexane (1 : 6) gave 9 (2.73 g). The
mother liquor of this recrystallization was concentrated and the residual oil was purified by flash
chromatography [AcOEt–hexane (1 : 3)] to furnish a second crop of 9 (1.45 g). The total yield of 9 was
4.18 g (92%). Further recrystallization from hexane afforded an analytical sample as colorless scales,
mp 86.5–87.5 °C; ["] 28 –43.0° (c 0.99, MeOH); MS m/z: 302 (M+); IR (Nujol) #, cm–1: 1675 (carbamate
D
CO); 1H-NMR (CDCl3) !: 1.42 (9H, s, CMe3), 1.45 (3H, d, J = 7.3 Hz, CHMe), 4.2 and 4.35 (2H, br each,
CH2Ph), 5.64 (1H, br, CHMe), 6.88 [1H, s, C(4)-H], 7.1–7.3 (5H, m, Ph), 7.70 [1H, s,
C(2)-H]. Anal. Calcd for C17H22N2O3: C, 67.53; H, 7.33; N, 9.26. Found: C, 67.55; H, 7.34; N, 9.29.

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HETEROCYCLES, Vol. 83, No. 6, 2011
(S)-N-Benzyl-"-methyl-5-oxazolemethanamine (10).
A mixture of 9 (986 mg, 3.3 mmol),
trifluoroacetic acid (9 mL), and CH2Cl2 (9 mL) was stirred at 0 °C for 1.5 h. The reaction mixture was
concentrated in vacuo, and the residue was dissolved in H2O. The aqueous solution was made basic with
K2CO3 and extracted with CHCl2. The CHCl3 extracts were dried and concentrated to leave 10 (635 mg,
27
96%) as a pale yellow oil, ["]
–73.9° (c 1.00, MeOH); MS m/z: 202 (M+); IR (film) #, cm–1: 3300
D
(NH); 1H-NMR (CDCl3) !: 1.45 (3H, d, J = 6.8 Hz, Me), 1.85 (1H, br, NH), 3.68 and 3.76 (2H, d each, J
= 13.2 Hz, CH2Ph), 3.97 (1H, q, J = 6.8 Hz, CHMe), 6.93 [1H, s, C(4)-H], 7.2–7.35 (5H, m, Ph), 7.83
[1H, s, C(2)-H]; HRMS calcd for C12H14N2O: 202.1106, found: 202.1105.
(S)-N-Benzyl-N-[1-(5-oxazolyl)ethyl]-3-butenamide (8). To a cooled solution of 10 (404 mg, 2.0
mmol) in DMF (6 mL) were added 3-butenoic acid (206 mg, 2.4 mmol), diethyl phosphorocyanidate (652
mg, 4.0 mmol), and Et3N (404 mg, 4.0 mmol). After stirring at 0 °C for 30 min, the reaction mixture
was partitioned between H2O and CHCl3. The CHCl3 extracts were washed successively with saturated
aqueous NaHCO3 and brine, dried, and concentrated. Purification of the residual oil by flash
21
chromatography [AcOEt–hexane (1 : 1)] gave 8 (414 mg, 77%) as a colorless oil, ["] –62.2° (c 1.01,
D
MeOH); MS m/z: 270 (M+); IR (film) #, cm–1: 1640 (amide CO); 1H-NMR (CDCl ) !: 1.44 and 1.50 (3H,
3
d each, J = 7.3 Hz, Me), 3.09 and 3.42 (2H, br d each, J = 6.3 Hz, COCH2), 4.27, 4.63 (d each, J = 15.6
Hz) and 4.35, 4.51 (d each, J = 17.8 Hz) (2H, CH2Ph), 5.04 (d, J = 17.6 Hz), 5.15 (d, J = 10.3 Hz), and
5.2–5.3 (m) (2H, CH=CH2), 5.98 (1H, m, CH=CH2), 6.15 (1H, q, J = 7.3 Hz, CHMe), 6.93 [1H, s,
C(4)-H], 7.05–7.35 (5H, m, Ph), 7.70 [1H, s, C(2)-H]; HRMS calcd for C16H18N2O2: 270.1368, found:
270.1366.
(S)-N-Benzyl-N-[1-(5-oxazolyl)ethyl]-2-butenamide (3a). A mixture of a solution of 10 (1.37 g, 6.8
mmol) in benzene (30 mL) and a solution of Na2CO3 (789 mg, 7.4 mmol) in H2O (30 mL) was stirred
under ice-cooling, and a solution of crotonoyl chloride (920 mg, 8.8 mmol) in benzene (10 mL) was
added dropwise over 15 min. After the mixture had been stirred for 30 min, the benzene layer was
separated from the aqueous layer, which was extracted with benzene. The combined benzene solutions
were washed successively with saturated aqueous NaHCO3 and brine, dried, and concentrated to leave a
yellow oil. Purification of the oil by flash chromatography [AcOEt–hexane (2 : 1)] provided 3a (1.51 g,
82%) as a colorless oil, ["] 24 –91.0° (c 1.02, MeOH); MS m/z: 270 (M+); IR (film) #, cm-1: 1660 (amide
D
CO); 1H-NMR (CDCl3) !: 1.44 (3H, d, J = 6.8 Hz, NCHMe), 1.81 (3H, d, J = 6.3 Hz, CH=CHMe), 4.39
and 4.55 (2H, AB type d’s, J = 18.1 Hz, CH2Ph), 6.09 (1H, d, J = 14.7 Hz, CH=CHMe), 6.17 (1H, q, J =
6.8 Hz, NCHMe), 6.92 [1H, s, C(4)-H], 7.08 (1H, dq, J = 14.7, 6.3 Hz, CH=CHMe), 7.1–7.3 (5H, m, Ph),
7.68 [1H, s, C(2)-H]; HRMS calcd for C16H18N2O2: 270.1368, found: 270.1371.

HETEROCYCLES, Vol. 83, No. 6, 2011
1401
(S)-N-Benzyl-N-[1-(5-oxazolyl)ethyl]-2-propenamide (3b). The Schotten–Baumann reaction of 10
(294 mg, 1.5 mmol) with acryloyl chloride (172 mg, 1.9 mmol) and work-up of the reaction mixture were
26
carried out as described above for 3a, giving 3b (316 mg, 85%) as a colorless oil, ["] –87.0° (c 1.12,
D
MeOH); MS m/z: 256 (M+); IR (film) #, cm-1: 1651 (amide CO); 1H-NMR (CDCl ) !: 1.47 (3H, d, J = 6.8
3
Hz, Me), 4.42 and 4.57 (2H, AB type d’s, J = 18.1 Hz, CH2Ph), 5.69 (1H, d, J = 10.0 Hz) and 6.50 (1H, d,
J = 16.1 Hz) (CH=CH2), 6.18 (1H, q, J = 6.8 Hz, CHMe), 6.39 (1H, dd, J = 16.1, 10.0 Hz, CH=CH2),
6.95 [1H, s, C(4)-H], 7.1–7.3 (5H, m, Ph), 7.69 [1H, s, C(2)-H]; HRMS calcd for C15H16N2O2: 256.1211,
found: 256.1210.
(S)-2-Benzyl-2,3-dihydro-3,7-dimethyl-1H-pyrrolo[3,4-c]pyridin-1-one (4a). Entry 3 in Table 1: A
mixture of 3a (113 mg, 0.42 mmol) and Cu(OTf)2 (15.2 mg, 10 mol %) in o-DCB (8.4 mL) was heated at
120 °C in an atmosphere of Ar for 3 h. The reaction mixture was concentrated in vacuo, and the residual
oil was purified by flash chromatography (AcOEt) to give 4a (99 mg, 94%) as a yellow solid. The
1
enantiomeric purity of this solid was shown to be 98% ee by means of H-NMR spectroscopy using the
chiral shift reagent tris[3-(heptafluoropropylhydroxymethylene)-(+)-camphorato]europium(III) [Eu(hfc)3]
in CDCl3. Recrystallization from AcOEt–hexane (1 : 1) furnished an analytical sample as colorless
prisms, mp 89.5–91.5 °C; ["] 23 –123° (c 0.70, MeOH); IR (Nujol) #, cm-1: 1672 (lactam CO); 1H-NMR
D
(CDCl3) !: 1.47 (3H, d, J = 6.8 Hz, CHMe), 2.74 [3H, s, C(7)-Me], 4.25 and 5.30 (2H, d each, J = 14.9
Hz, CH2Ph), 4.45 (1H, q, J = 6.8 Hz, CHMe), 7.25–7.35 (5H, m, Ph), 8.51 and 8.55 [1H each, s, C(4)-H
and C(6)-H]. Anal. Calcd for C16H16N2O: C, 76.17; H, 6.39; N, 11.10. Found: C, 76.07; H, 6.39; N,
11.10.
(S)-2-Benzyl-2,3-dihydro-3-methyl-1H-pyrrolo[3,4-c]pyridin-1-one (4b). Entry 7 in Table 1: A
mixture of 3b (143 mg, 0.56 mmol) and Cu(OTf)2 (4.1 mg, 2 mol %) in o-DCB (11.2 mL) was heated at
150 °C in an atmosphere of Ar for 5 h. The reaction mixture was concentrated in vacuo to leave a
brown oil. Purification of the oil by flash chromatography (AcOEt) afforded 4b (9.3 mg, 7%) as a pale
26
brown oil, ["]
–102.9° (c 0.24, MeOH); MS m/z: 238 (M+); IR (film) #, cm-1: 1685 (lactam CO);
D
1H-NMR (CDCl ) !: 1.50 (3H, d, J = 6.8 Hz, Me), 4.27 and 5.35 (2H, d each, J = 15.1 Hz, CH2Ph), 4.51
3
(1H, q, J = 6.8 Hz, CHMe), 7.25–7.35 (5H, m, Ph), 7.78 [1H, d, J = 4.9 Hz, C(7)-H], 8.76 [1H, s, C(4)-H],
8.78 [1H, d, J = 4.9 Hz, C(6)-H]; HRMS calcd for C15H14N2O: 238.1106, found: 238.1103. The
enantiomeric purity of this oil was estimated to be 98% ee in the same manner as described for 4a.
(S)-N-(Diphenylmethylene)-"-methyl-5-oxazolemethanamine (14). A mixture of 64 (114 mg, 1.0
mmol) and benzophenone imine (203 mg, 1.1 mmol) in CH2Cl2 (4 mL) was stirred at rt for 24 h. The

1402
HETEROCYCLES, Vol. 83, No. 6, 2011
reaction mixture was concentrated in vacuo to leave a yellow oil. Purification by flash chromatography
25
[AcOEt–hexane (1 : 2)] furnished 14 (270 mg, 96%) as a yellow oil, ["]
–186° (c 0.51, MeOH); MS
D
m/z: 276 (M+); IR (film) #, cm-1: 1620 (C=N); 1H-NMR (CDCl3) !: 1.51 (3H, d, J = 6.4 Hz, Me), 4.67 (1H,
q, J = 6.4 Hz, CHMe), 6.91 [1H, s, C(4)-H], 7.2–7.65 (10H, m, two Ph’s), 7.80 [1H, s, C(2)-H]; HRMS
calcd for C18H16N2O: 276.1263, found: 276.1262.
(S)-N-(Diphenylmethyl)-"-methyl-5-oxazolemethanamine (15). A solution of 14 (780 mg, 2.8 mmol)
in MeOH (15 mL) was brought to pH 6 by the addition of AcOH, and NaCNBH3 (354 mg, 5.6 mmol) was
added in portions. The reaction mixture was then stirred at rt for 5 h, made basic with K2CO3 after the
addition of H2O (20 mL), and extracted with CHCl3. The CHCl3 extracts were dried and concentrated.
The residual oil was purified by flash chromatography [AcOEt–hexane (1 : 2)] to give 15 (611 mg, 78%)
as a colorless solid. Recrystallization from hexane afforded an analytical sample as colorless fluffy
24
1
needles, mp 39–41 °C; ["] –67.6° (c 0.49, MeOH); IR (Nujol) #, cm-1: 3280 (NH); H-NMR (CDCl3)
D
!: 1.45 (3H, d, J = 6.8 Hz, Me), 3.83 (1H, q, J = 6.8 Hz, CHMe), 4.75 (1H, s, CHPh ), 6.84 [1H, s,
2
C(4)-H], 7.15–7.4 (10H, m, two Ph’s), 7.82 [1H, s, C(2)-H]. Anal. Calcd for C18H18N2O: C, 77.67; H,
6.52; N, 10.06. Found: C, 77.68; H, 6.54; N, 10.03.
(S)-N-(Diphenylmethyl)-N-[1-(5-oxazolyl)ethyl]-2-propenamide (3c). A mixture of 15 (195 mg, 0.70
mmol), Et2N (119 mg, 1.2 mmol), DMAP (9 mg), acryloyl chloride (89 mg, 0.98 mmol), and benzene (10
mL) was stirred at rt for 1.5 h. The reaction mixture was then washed successively with saturated
aqueous NaHCO2 and brine, dried, and concentrated. Purification of the residual oil by flash
chromatography [AcOEt–hexane (1 : 1)] gave 3c (205 mg, 88%) as a colorless oil, ["] 24 –27.6° (c 0.62,
D
MeOH); MS m/z: 332 (M+); IR (film) #, cm-1: 1682 (amide CO); 1H-NMR (CDCl ) !: 1.53 (3H, d, J = 7.3
3
Hz, Me), 5.38 (1H, br, CHPh2), 6.05 (2H, br) and 6.26 (1H, d, J = 15.8 Hz) (CH=CH2), 6.1 (1H, br,
CHMe), 6.97 [1H, s, C(4)-H], 7.0–7.4 (10H, m, two Ph’s), 7.67 [1H, s, C(2)-H]; HRMS calcd for
C21H20N2O2: 332.1524, found: 332.1528.
(S)-2-(Diphenylmethyl)-2,3-dihydro-3-methyl-1H-pyrrolo[3,4-c]pyridin-1-one (4c). Entry 8 in Table
1: A solution of 3c (110 mg, 0.33 mmol) in o-DCB (6.6 mL) was heated at 180 °C in an atmosphere of Ar
for 1.5 h. The reaction mixture was concentrated in vacuo, and the residual oil was purified by flash
chromatography [AcOEt–hexane (6 : 1)] to provide 4c (26 mg, 25%) as a pale brown oil, ["] 24 +48.0° (c
D
0.13, MeOH); MS m/z: 314 (M+); IR (film) #, cm-1: 1685 (lactam CO); 1H-NMR (CDCl3) !: 1.37 (3H, d, J
= 6.7 Hz, Me), 4.57 (1H, q, J = 6.7 Hz, CHMe), 6.69 (1H, s, CHPh2), 7.2–7.4 (10H, m, two Ph’s), 7.75

HETEROCYCLES, Vol. 83, No. 6, 2011
1403
[1H, d, J = 4.9 Hz, C(7)-H], 8.73 [1H, s, C(4)-H], 8.77 [1H, d, J = 4.9 Hz, C(6)-H]; HRMS calcd for
C21H18N2O: 314.1419, found: 314.1416.
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