A one-step synthesis of enantiopure 2-substituted 4,5-dihydro-1,4-benzodiazepine-3-ones via intramolecular azide cycloaddition

Article abstract of DOI:10.1016/j.tetasy.2007.05.015

Starting from the appropriate azides bearing the (S)-1-phenylethylamine and the l-alanine benzylester as chiral pendants, a facile and effective synthetic route to the title compounds in their enantiopure form was developed with excellent product yields o

Full text of DOI:10.1016/j.tetasy.2007.05.015

Tetrahedron: Asymmetry 18 (2007) 1197–1201
A one-step synthesis of enantiopure 2-substituted 4,5-dihydro-1,4-
benzodiazepine-3-ones via intramolecular azide cycloaddition
Giorgio Molteni* and Paola Del Buttero
`
Universita degli Studi di Milano, Dipartimento di Chimica Organica e Industriale, via Golgi 19, 20133 Milano, Italy
Received 3 April 2007; accepted 16 May 2007
Abstract—Starting from the appropriate azides bearing the (S)-1-phenylethylamine and the L-alanine benzylester as chiral pendants, a
facile and effective synthetic route to the title compounds in their enantiopure form was developed with excellent product yields obtained.
Basic hydrolysis of the ester group of the title compounds 3a–c gave the corresponding, readily functionalisable carboxylic acids. Catalytic
reduction of 2-benzyl derivatives 3c and 3f gave 4-functionalised 1,2,4,5-tetrahydro-1,4-benzodiazepin-3-ones in enantiopure forms.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Intramolecular 1,3-dipolar cycloadditions have been recog-
nised as a powerful tool, leading to a large variety of both
cyclic and open-chain molecules.1 In recent years, the ste-
reoselective version of these reactions have constituted as
a key step in a number of syntheses of enantiopure mole-
cules, which would be difficult to obtain by different
routes.2 Among the variety of available 1,3-dipolar species,
stereoselective intramolecular azide cycloadditions play a
key role in the construction of a number of valuable
synthetic targets.1c,2 Some examples of great interest are
pyrrolizidine and indolizidine alkaloids,3 clavicipitic acids4
and biotin.5 All of these synthetic approaches rely on the
thermal degradation of the first-formed azide-alkene cyc-
loadduct, namely the 4,5-dihydro-1,2,3-triazole ring, which
usually shows low stability under the cycloaddition condi-
tions.6 This behaviour was herein investigated further with
the aim of realizing an efficient, single-step synthesis of
enantiopure 2-substituted 4,5-dihydro-1,4-benzodiazepine-
3-ones starting from the appropriate homochiral azides.
These heterocycles were further reacted to give readily
functionalisable hydroxycarbonyl derivatives, as well as
tetrahydro-1,4-benzodiazepine-3-ones. It should be noted
that the latter compounds are of biological interest because
they can act as fibrinogen receptor antagonists,7 angio-
tensin analogues8 and protein kinase C activators.9
Homochiral azides 1a, 1c, 1d and 1f (Scheme 1) were read-
ily obtained through literature procedures10 from the corre-
sponding anilines by diazotisation of the latter, followed by
treatment with sodium azide. The novel N-alkenoyl arylaz-
ides 1b and 1e were obtained in the same way with almost
quantitative yields (see Section 4). Thermal treatment of
1a–f in dry toluene and in the presence of a catalytic
amount of PTSA (0.02 mol equiv) gave pure 3 with very
good yields (92–98%) after crystallisation with diisopropyl
ether. Structures 3 were deduced unambiguously from the
analytical and spectral data. In particular, all the spectral
data of the novel 2-substituted 4,5-dihydro-1,4-benzo dia-
zepine-3-ones 3b, 3c, 3e and 3f agrees perfectly with those
reported for the known 3a, 3d10 and other closely related
achiral compounds.11
These results deserves some comments in order to account
for the exclusive formation of compounds 3. It should be
noted that the intramolecular cycloaddition of the azido
group onto the ethylenic bond form a tricyclic structure
containing a 4,5-dihydro-1,2,3-triazole ring.1,2 Further-
more, it has been well documented that, due to their ther-
mal lability, 4,5-dihydro-1,2,3-triazoles undergo facile loss
of nitrogen.6a,b On the basis of a number of previous
studies dealing with the mechanistic aspects of nitrogen
extrusion from 4,5-dihydro-1,2,3-triazoles, it is reasonable
to assume the occurrence of the 1,3-dipolar intermediate
A as a transient species (Scheme 2).6 To this point, the
fate of intermediate A follows two different pathways: (i)
*
Corresponding author. Tel.: +39 02 51314141; fax: +39 02 50314139;
e-mail: giorgio.molteni@unimi.it
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.05.015

1198
G. Molteni, P. Del Buttero / Tetrahedron: Asymmetry 18 (2007) 1197–1201
N
N
N
1
1
R
R
N3
N
1
PTSA (2% mol)
R
O
R
O
R
toluene, Δ
(-N2)
N
N
N
O
Me
Me
Me
R
1
2
3
Entry
R
a
b
c
d
e
f
COOBn
H
COOBn
Me
COOBn
Ph
Ph
H
Ph
Me
Ph
Ph
1
R
Scheme 1.
3
1
R
N
H
1
1
R
R
2
O
H
(-
N2)
N
N
N
H
H
O
R
+
H
+
H
-
3
O
Me
N
N
A
R
R
Me
Me
4
Scheme 2.
prototropic migration to give the final product 3, and (ii)
ring closure to the aziridino[2,1-c][1,4]benzo diazepinones
4. As a matter of fact, thermal decomposition of primary
cycloadducts 2a and 2d carried out in a previous work,10
gave mixtures of the corresponding products 3 and 4. To
address the above azide-alkene cycloaddition protocol to
a more preparative target, it was argued that the presence
of a catalytic amount of PTSA could be effective in order
to promote the transformation 4!3 through the mechanis-
tic pathway outlined in Scheme 2.
As a further step of this work, 2-benzyl derivatives 3c and
3f were submitted to catalytic hydrogenation giving 4-func-
tionalised 1,2,4,5-tetrahydro-1,4-benzodiazepin-3-ones 6
and 7 in the enantiopure forms. It should be noted that
upon hydrogenation in methanol in the presence of 10%
Pd/C at room temperature and 15 psi of pressure, cleavage
of the benzylester group was paralleled by the unexpected
loss of the benzyl substituent at the 2-position of the 1,4-
benzo diazepine-3-one ring (Scheme 4).
To provide the 4,5-dihydro-1,4-benzodiazepine-3-one scaf-
fold with a readily functionalisable functional group, com-
pounds 3a–c were submitted to a basic hydrolysis of the
benzylester group under mild conditions (1:1 aqueous so-
dium hydroxide–tetrahydrofuran at room temperature) to
give the corresponding carboxylic acids 5a–c (Scheme 3).
H
N
H2, 10%Pd(OH)2/C
3c,f
O
R
MeOH
N
Me
6: R = COOH
7: R = Ph
1
R
N
1M aq. NaOH/THF
3a-c
O
Scheme 4.
N
COOH
Me
3. Conclusion
a: R = H, b: R = Me, c: R = Ph
5a-c
The intramolecular cycloadditions of homochiral N-
alkenoyl-aryl azides 1 gave enantiopure 2-substituted
Scheme 3.

G. Molteni, P. Del Buttero / Tetrahedron: Asymmetry 18 (2007) 1197–1201
1199
4,5-dihydro-1,4-benzodiazepin-3-ones 3 by in situ thermal
decomposition of 3,3a,5,6-tetrahydro[1,2,3]triazolo[1,5-a]-
[1,4]benzodiazepin-4-ones 2 as the primary cycloadducts.
Further transformations of target products 3 provided a
clean synthetic entry to enantiopure compounds 5–7 of
potential pharmacological interest.
Calcd for C19H20N4O: C, 71.23; H, 6.29; N, 17.49. Found:
C, 71.27; H, 6.33; N, 17.53.
4.2. Thermal behaviour of N-alkenoyl aryl azides 1a–e in the
presence of catalytic amounts of PTSA
A solution of N-alkenoyl aryl azides 1a–e (5.0 mmol) and
PTSA (17 mg, 0.1 mmol) in dry toluene (250 mL) was
refluxed under a nitrogen atmosphere for 4 h. Evaporation
of the solvent gave a residue that was crystallised with
diisopropylether to give pure 3a–e.
4. Experimental
Melting points were determined with a Buchi apparatus in
¨
open tubes and are uncorrected. IR spectra were recorded
with a Perkin–Elmer 1725 X spectrophotometer. Mass
4.2.1.
2-Methyl-4-[1-(S)-(1-benzyloxycarbonyl)ethyl]-4,5-
1
spectra were determined with a VG-70EQ apparatus. H
dihydro-1,4-benzodiazepine-3-one 3a. 1.51 g, 95%.10
NMR (300 MHz) and 13C NMR (75 MHz) spectra were
taken with a Bruker AMX 300 instrument (in CDCl3 solu-
tions at room temperature). Chemical shifts are given as
4.2.2.
2-Ethyl-4-[1-(S)-(1-benzyloxycarbonyl)ethyl]-4,5-
dihydro-1,4-benzodiazepine-3-one 3b. 1.68 g, 96%. White
parts per million from tetramethylsilane and J values are
powder, mp 76–78 ꢁC (from diisopropyl ether).
25
25
given in Hertz. Optical rotations, ½aꢀD , were recorded on
½aꢀD ¼ þ241:0 (c 0.22, CHCl3); IR (Nujol) 1740,
a Perkin–Elmer 241 polarimeter at the sodium D-line.
1650 cmꢁ1 1H NMR d: 1.21 (3H, t, J 8.1, CH3CH2–),
;
1.44 (3H, d, J 7.7, CH3–CH—), 2.90 (2H, t, J 8.1,
CH3CH2–), 4.10 (2H, s, –CH2–), 5.15 (2H, s, –OCH2Ph),
5.36 (1H, q, J 7.7, CH3–CH—), 6.8–7.4 (9H, m, aromatics);
13C NMR d: 19.80 (q), 20.48 (q), 22.55 (t), 49.80 (q), 51.28
(t), 52.20 (d), 126.0–130.0, 136.50 (s), 137.88 (s), 140.21 (s),
148.18 (s), 169.70 (s), 173.44 (s). MS m/z: 350 (M+). Anal.
Calcd for C21H22N2O3: C, 71.98; H, 6.33; N, 7.99. Found:
C, 72.03; H, 6.34; N, 8.06.
Compounds 1a, 1c, 1d and 1f10 and 3a and 3d10 are already
known in the literature.
4.1. Synthesis of N-alkenoyl aryl azides 1b and 1e
A
solution of 2-[N-(1-(S)-phenylethyl)-N-(1-oxo-2-(E)-
butenyl)]aminomethyl aniline12 or 2-{N-[1-(S)-(1-benzyl-
oxycarbonyl)ethyl]-N-(1-oxo-2-(E)-butenyl)}aminomethyl
aniline12 (10.0 mmol) in aqueous hydrochloric acid (6 M,
8.0 mL) and acetic acid (4.0 mL) was treated with sodium
nitrite (1.04 g, 15.0 mmol) under stirring and cooling at
0–5 ꢁC. After 30 min, the mixture was treated with cold
diethyl ether (25 mL) and sodium azide (3.22 g, 0.05 mol)
was added portionwise under vigorous stirring and ice-
cooling. After 1 h, the organic layer was separated, washed
with 5% aqueous sodium hydrogen carbonate (30 mL),
then with water (50 mL) and dried over sodium sulfate.
Evaporation of the solvent gave crude products 1b and
1e. The residue was chromatographed on a silica gel col-
umn with hexane–AcOEt (2:1) to give pure 1b and 1e.
4.2.3.
2-Benzyl-4-[1-(S)-(1-benzyloxycarbonyl)ethyl]-4,5-
dihydro-1,4-benzodiazepine-3-one 3c. 1.90 g, 92%. White
powder, mp 64–65 ꢁC (from diisopropyl ether).
25
½aꢀD ¼ þ135:1 (c 0.20, CHCl3); IR (Nujol) 1735,
1
1660 cmꢁ1; H NMR d: 1.40 (3H, d, J 7.8, CH3–CH—),
2.87 (2H, s, –CH2–Ph), 4.25 (2H, s, –CH2–), 5.10 (2H, s,
–OCH2Ph), 5.44 (1H, q, J 7.8, CH3–CH—), 6.1–7.4 (14H,
m, aromatics); 13C NMR d: 21.16 (q), 27.98 (t), 51.11 (q),
54.55 (t), 57.12 (d), 125.0–132.0, 135.66 (s), 137.00 (s),
142.23 (s), 147.62 (s), 170.80 (s), 176.23 (s). MS m/z: 412
(M+). Anal. Calcd for C26H24N2O3: C, 75.71; H, 5.86; N,
6.79. Found: C, 77.76; H, 5.90; N, 7.84.
4.1.1. 2-{N-[1-(S)-(1-Benzyloxycarbonyl)ethyl]-N-(1-oxo-2-
(E)-butenyl)}methylamino phenylazide 1b. 3.40 g, 90%.
4.2.4. 2-Methyl-4-(1-(S)-phenylethyl)-4,5-dihydro-1,4-benzo-
diazepine-3-one 3d. 1.32 g, 95%.10
25
Yellow oil. ½aꢀD ¼ ꢁ15:2 (c 0.21, CHCl3); IR (neat) 2130,
1
1740 cmꢁ1; H NMR d: 1.41 (3H, d, J 7.1, CH3–CH—), 1.82
4.2.5. 2-Ethyl-4-(1-(S)-phenylethyl)-4,5-dihydro-1,4-benzo-
diazepine-3-one 3e. 1.43 g, 98%. White powder, mp 91–
(3H, d, J 7.2, CH3–CH@), 4.40 (1H, d, J 17.5, –CH2–),
4.58 (1H, d, J 17.5, –CH2–), 5.11 (1H, q, J 7.1,
CH3–CH—), 5.18 (2H, s, –OCH2Ph), 6.17 (1H, dd, J 15.4,
7.1, –CH@), 6.8–7.4 (9H, m, aromatics), 7.70 (1H, d, J
15.4, –CO–CH@). MS m/z: 378 (M+). Anal. Calcd for
C21H22N4O3: C, 66.65; H, 5.86; N, 14.81. Found: C,
66.69; H, 5.90; N, 14.88.
25
93 ꢁC (from diisopropyl ether). ½aꢀD ¼ þ54:6 (c 0.24,
1
CHCl3); IR (neat) 1630 cmꢁ1; H NMR d: 1.22 (3H, d, J
8.0, CH3CH2–), 1.72 (3H, d, J 7.7, CH3–CH—), 2.76 (2H,
t, J 8.0, CH3CH2–), 4.24 (1H, d, J 16.8, –CH2–), 4.38
(1H, d, J 16.8, –CH2–), 5.66 (1H, q, J 7.7, CH3–CH—),
7.0-7.5 (9H, m, aromatics); 13C NMR d: 18.87 (q), 20.56
(q), 23.37 (t), 50.85 (t), 52.45 (d), 123.0–130.0, 136.60 (s),
137.90 (s), 140.10 (s), 148.23 (s), 168.85 (s). MS m/z: 292
(M+). Anal. Calcd for C19H20N2O: C, 78.05; H, 6.89; N,
9.58. Found: C, 78.09; H, 6.92; N, 9.64.
4.1.2.
2-[N-(1-(S)-Phenylethyl)-N-(1-oxo-2-(E)-butenyl)]-
methylamino phenylazide 1e. 2.88 g, 92%. Orange oil.
25
½aꢀD ¼ ꢁ66:0 (c 0.24, CHCl3); IR (neat) 2130, 1660 cmꢁ1
;
1H NMR d: 1.38 (3H, d, J 7.7, CH3–CH—), 1.80 (3H, d,
J 7.0, CH3–CH@), 4.20 (1H, d, J 17.9, –CH2–), 4.32 (1H,
d, J 17.9, –CH2–), 5.84 (1H, q, J 7.7, CH3–CH—), 6.50
(1H, dd, J 15.3, 7.0, –CH@), 6.8–7.4 (9H, m, aromatics),
7.75 (1H, d, J 15.3, –CO–CH@). MS m/z: 320 (M+). Anal.
4.2.6. 2-Benzyl-4-(1-(S)-phenylethyl)-4,5-dihydro-1,4-benzo-
diazepine-3-one 3f. 1.72 g, 97%. White powder, mp 73–
25
75 ꢁC (from diisopropyl ether). ½aꢀD ¼ þ107:1 (c 0.14,
1
CHCl3); IR (neat) 1650 cmꢁ1; H NMR d: 1.83 (3H, d,

1200
G. Molteni, P. Del Buttero / Tetrahedron: Asymmetry 18 (2007) 1197–1201
J 7.6, CH3–CH—), 2.85 (2H, s, –CH2–Ph), 4.20 (1H, d, J
17.9, –CH2–), 4.35 (1H, d, J 17.9, –CH2–), 5.42 (1H, q, J
7.6, CH3–CH—), 6.7–7.6 (14H, m, aromatics); 13C NMR
d: 21.67 (q), 27.17 (t), 51.36 (t), 52.80 (d), 122.0–129.0,
136.34 (s), 137.88 (s), 138.12 (s), 139.20 (s), 148.76 (s),
169.85 (s). MS m/z: 354 (M+). Anal. Calcd for
C24H22N2O: C, 81.33; H, 6.26; N, 7.90. Found: C, 81.37;
H, 6.29; N, 7.98.
4.4. Catalytic hydrogenation of 2-substituted-4,5-dihydro-
1,4-benzodiazepine-3-ones 3c and 3f
A solution of 3c or 3f (0.5 mmol) in MeOH (20 mL) was
treated with 10% Pd(OH)2/C (0.14 g) and stirred under a
hydrogen atmosphere (15 psi) for 24 h. The mixture was fil-
tered through a Celite pad, and the solvent was removed
under reduced pressure and the residue chromatographed
on silica gel column with hexane–AcOEt (2:1) to afford
1,2,4,5-tetrahydro-1,4-benzodiazepin-3-ones 6 and 7.
4.3. Basic hydrolysis of 2-substituted-4,5-dihydro-1,4-benzo-
diazepine-3-ones 3a–c
4.4.1. 4-[1-(S)-(1-Hydroxycarbonyl)ethyl]-1,2,4,5-tetrahy-
dro-1,4-benzodiazepine-3-one 6. 50 mg, 43%. Pale yellow
A solution of 3a–c (1.2 mmol) in tetrahydrofuran (25 mL)
and 1 M aqueous sodium hydroxide (25 mL) was stirred
at room temperature for 5 h. Aqueous hydrochloric acid
(1 M) was added to pH 3 and the mixture was extracted
with ethyl acetate (3 · 50 mL). The organic layer was
washed with water (50 mL), dried over sodium sulfate
and evaporated. Crystallisation from isopropanol gave
pure 5a–c.
powder,
mp
116–118 ꢁC
(from
diisopropanol).
25
½aꢀD ¼ ꢁ35:1 (c 0.77, CHCl3); IR (Nujol) 3240, 1710,
1645 cmꢁ1; H NMR d: 1.43 (3H, d, J 8.1, CH3–CH—),
1
3.95 (1H, d, J 14.6, –HN–CH2–), 4.12 (1H, br s, –NH),
4.27 (1H, d, J 16.6, –CH2–), 4.38 (1H, d, J 14.6, –HN–
CH2–), 4.86 (1H, d, J 16.6, –CH2–), 5.36 (1H, q, J 8.1,
CH3–CH—), 6.5–7.1 (4H, m, aromatics), 10.40 (1H, br s,
–COOH); 13C NMR d: 21.93 (q), 27.19 (t), 38.16 (t),
56.37 (d), 125.0–131.0, 136.45 (s), 137.81 (s), 168.10 (s),
179.22 (s). MS m/z: 234 (M+). Anal. Calcd for
C12H14N2O3: C, 61.53; H, 6.02; N, 11.96. Found: C,
61.57; H, 5.98; N, 12.02.
4.3.1.
dihydro-1,4-benzodiazepine-3-one 5a. 0.22 g, 75%. White
powder, mp (from diisopropanol).
2-Methyl-4-[1-(S)-(1-hydroxycarbonyl)ethyl]-4,5-
112–114 ꢁC
25
½aꢀD ¼ þ76:0 (c 0.17, CHCl3); IR (Nujol) 3340, 1700,
1660 cmꢁ1; H NMR d: 1.36 (3H, d, J = 7.9, CH3–CH—),
1
4.4.2. 4-[(1-(S)-(1-Phenylethyl)]-1,2,4,5-tetrahydro-1,4-ben-
zodiazepine-3-one 7. 52 mg, 39%. Pale yellow powder,
2.59 (3H, s, CH3–), 4.16 (2H, s, –CH2–), 5.33 (1H, q, J
7.9, CH3–CH—), 7.1–7.4 (4H, m, aromatics), 10.80 (1H,
br s, –COOH); 13C NMR d: 20.31 (q), 23.12 (q), 48.87
(t), 51.82 (d), 127.0–131.0, 136.22 (s), 140.88 (s), 148.36
(s), 168.37 (s), 180.20 (s). MS m/z: 246 (M+). Anal. Calcd
for C13H14N2O3: C, 63.40; H, 5.73; N, 11.38. Found: C,
63.44; H, 5.76; N, 11.43.
25
mp 85–87 ꢁC (from diisopropyl ether). ½aꢀD ¼ ꢁ107:1 (c
0.14, CHCl3); IR (Nujol) 3230, 1715, 1655 cmꢁ1 1H
;
NMR d: 1.49 (3H, d, J 7.9, CH3–CH—), 4.03 (1H, d, J
14.6, –HN–CH2–), 4.10 (1H, br s, –NH), 4.22 (1H, d, J
16.7, –CH2–), 4.35 (1H, d, J 14.6, –HN–CH2–), 4.44 (1H,
d, J 16.7, –CH2–), 6.02 (1H, q, J 7.9, CH3–CH—), 6.5–7.4
(9H, m, aromatics); 13C NMR d: 20.16 (q), 30.15 (t),
41.12 (t), 53.87 (d), 126.0–132.0, 135.22 (s), 138.11 (s),
171.36 (s), 180.98 (s). MS m/z: 266 (M+). Anal. Calcd for
C17H18N2O: C, 76.66; H, 6.81; N, 10.52. Found: C,
76.80; H, 6.78; N, 10.57.
4.3.2. 2-Ethyl-4-[1-(S)-(1-hydroxycarbonyl)ethyl]-4,5-dihy-
dro-1,4-benzodiazepine-3-one 5b. 0.27 g, 87%. White pow-
25
der, mp 93–94 ꢁC (from diisopropanol). ½aꢀD ¼ þ129:6 (c
0.23, CHCl3); IR (Nujol) 3350, 1710, 1660 cmꢁ1 1H
;
NMR d: 1.16 (3H, t, J 8.0, CH3–CH—), 1.48 (3H, d, J
7.8, CH3CH2–), 2.46 (2H, q, J 8.0, CH3–CH2–), 4.33
(2H, s, –CH2–), 5.21 (1H, q, J 7.8, CH3–CH—), 7.0–7.4
(4H, m, aromatics), 10.50 (1H, br s, –COOH); 13C NMR
d: 21.33 (q), 20.67 (q), 22.40 (t), 51.16 (t), 53.24 (d),
125.0–131.0, 136.43 (s), 140.70 (s), 148.94 (s), 168.89 (s),
182.34 (s). MS m/z: 260 (M+). Anal. Calcd for
C14H16N2O3: C, 64.60; H, 6.20; N, 10.76. Found: C,
64.64; H, 6.23; N, 10.83.
Acknowledgment
Thanks are due to MURST (PRIN funding) for financial
support.
References
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Dipolar Cycloaddition Chemistry Toward Heterocycles and
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2. (a) Gothelf, K. V.; Jørgensen, K. A. Chem. Rev. 1998, 98,
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4.3.3. 2-Benzyl-4-[1-(S)-(1-hydroxycarbonyl)ethyl]-4,5-dihy-
dro-1,4-benzodiazepine-3-one 5c. 0.30 g, 78%. White pow-
der having mp 163–165 ꢁC (from diisopropanol).
25
½aꢀD ¼ þ289:6 (c 0.38, CHCl3); IR (Nujol) 3340, 1710,
1
1650 cmꢁ1; H NMR d: 1.76 (3H, d, J 7.9, CH3–CH—),
2.75 (2H, s, –CH2–Ph), 4.28 (2H, s, –CH2–), 5.20 (1H, q,
J 7.9, CH3–CH—), 7.1–7.4 (9H, m, aromatics), 10.55 (1H,
br s, –COOH); 13C NMR d: 20.85 (q), 25.95 (t), 50.55 (t),
53.67 (d), 125.0–131.0, 136.20 (s), 137.90 (s), 140.38 (s),
148.76 (s), 167.58 (s), 181.10 (s). MS m/z: 322 (M+). Anal.
Calcd for C19H18N2O3: C, 70.79; H, 5.63; N, 8.69. Found:
C, 70.83; H, 5.60; N, 8.75.

G. Molteni, P. Del Buttero / Tetrahedron: Asymmetry 18 (2007) 1197–1201
1201
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