A convenient trans diastereoselective synthesis of 3-butadienylazetidinones and their Diels-Alder cycloaddition reactions

Article abstract of DOI:10.1021/jo952249i

An efficient trans diastereoselective synthesis for azetidinones 3 having 3-dienyl functionalities was developed. The method first involved the [2 + 2] cycloaddition of butadienylketene with various imines 1. The 3-dienyl functionality of the resulting azetidinones 3 was then exploited in Diels-Alder cycloaddition reactions with dienophiles, viz. dimethyl acetylenedicarboxylate (DMAD), maleic anhydride (MA), N-phenylmaleimide (NPM), and 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD). The reactions of 3 with DMAD and PTAD resulted in the diastereoselective synthesis of the corresponding Diels-Alder adducts 5a,b and 6. However, the reactions with MA and NPM yielded a mixture (2:1) of diastereoisomers 7/7' and 8/8'.

Full text of DOI:10.1021/jo952249i

5
506
J . Org. Chem. 1996, 61, 5506-5509
A Con ven ien t Tr a n s Dia ster eoselective Syn th esis of
-Bu ta d ien yla zetid in on es a n d Th eir Diels-Ald er Cycloa d d ition
Rea ction s
3
Arun K. Sharma, Sujit N. Mazumdar, and Mohinder P. Mahajan*
Department of Chemistry, North-Eastern Hill University, Shillong-793 003, Meghalaya, India
Received December 20, 1995X
An efficient trans diastereoselective synthesis for azetidinones 3 having 3-dienyl functionalities
was developed. The method first involved the [2 + 2] cycloaddition of butadienylketene with various
imines 1. The 3-dienyl functionality of the resulting azetidinones 3 was then exploited in Diels-
Alder cycloaddition reactions with dienophiles, viz. dimethyl acetylenedicarboxylate (DMAD), maleic
anhydride (MA), N-phenylmaleimide (NPM), and 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD). The
reactions of 3 with DMAD and PTAD resulted in the diastereoselective synthesis of the
corresponding Diels-Alder adducts 5a ,b and 6. However, the reactions with MA and NPM yielded
a mixture (2:1) of diastereoisomers 7/7′ and 8/8′.
The importance and structural diversity of biologically
course of ongoing investigations concerning azadiene-
9
active â-lactam antibiotics led to the development of
many novel methods for the construction of appropriately
substituted azetidin-2-ones with attendent control of
ketene cycloadditions in our laboratory, we have discov-
ered that the use of butadienylketene in such cycloaddi-
tions is an efficient route to the synthesis of dienyl-
substituted heterocycles. Given the synthetic possibilities
offered by functionalized 1,3-butadienes and the biologi-
cal importance of â-lactams in general and R-substituted
â-lactams in particular, we were prompted to initiate a
study of reactions of Schiff bases with butadienylketene.
As an entry into this area we describe here the diaste-
reoselective synthesis of R-butadienyl â-lactams which
served as versatile synthetic intermediates for further
elaboration to a variety of targeted R-substituted â-lac-
tam derivatives.
1
functional groups and stereochemistry. In recent years
several natural monocyclic â-lactams were shown to
exhibit high activity against Gram negative organisms,1
suggesting that a suitably substituted monocyclic â-lac-
tam ring might perhaps be the minimum requirement
for biological activity.2 In view of the reported impor-
a,c
3
4
tance of 3-alkyl/3-acetyl â-lactams and 4-vinyl â-lactams
as intermediates in the synthesis of â-lactam antibiotics,
efforts to devise/improve synthesis of suitably substituted
â-lactams is an ongoing challenge and continues to
attract the attention of the synthetic community.
Ketene-imine cycloadditions are a well-documented,6
route to the synthesis of various â-lactam derivatives.5
Although there are numerous reports concerning [2 + 2]
It was reported that reactions of various Schiff bases
with vinyl/isopropenylketenes resulted in trans, cis, or a
mixture of trans and cis â-lactams.3
b,7,8
We observed that
reactions of Schiff bases 1 with butadienylketene, gener-
ated in situ from sorbyl chloride (2) in the presence of
triethylamine in methylene chloride at room tempera-
ture, resulted in stereoselective formation of previously
unknown 3-butadienyl â-lactams 3 in good yields (48-
cycloadditions of imines to ketenes, extended recently to
vinyl- and isopropenylketenes,3
b,7,8
to our knowledge there
is no such report involving butadienylketene. During the
X
Abstract published in Advance ACS Abstracts, J uly 1, 1996.
6
3%) (Scheme 1). The products were assigned the
(1) For reviews on â-lactam antibiotics, see: (a) Chemistry and
Biology of â-Lactam Antibiotics; Morin, R. B., Gorman, M., Eds.;
Academic Press: New York, 1982-1983; Vols. 1-3. (b) Recent
Advances in the Chemistry of â-Lactam Antibiotics; Brown, A. G.,
Roberts, S. M., Eds.; The Royal Society of Chemistry: Burlington
House; London, 1984. (c) Topics in Antibiotic Chemistry; Sammes, P.
G., Ed.; Ellis Horwood: New York, 1980; Vols. 3-4. (d) Southgate,
R.; Elson, S. In Progress in the Chemistry of Organic Natural Products;
Herz, W., Grisebach, H., Kirby, G. W., Tamm, Ch., Eds.; Springer-
Verlag: New York, 1985; Vol. 47, pp 1-106. (e) Durckheimer, W.;
Blumbach, J .; Lattrell, R.; Sheunemann, K. H. Angew. Chem., Int. Ed.
Engl. 1985, 24, 180. (f) Koppel, G. A. In Small Ring Heterocycles;
Hassner, A. Ed.; J ohn Wiley: New York, 1983; Part 2, pp 248-301.
Brown, A. G. Pure Appl. Chem. 1987, 59, 475.
azetidinone structure 3 on the basis of analytical and
spectral data. Their IR spectra exhibited a strong
-
1
absorption around 1735 cm characteristic of the â-lac-
1
tam ring. Their H NMR spectra showed, in addition to
aromatic protons, the presence of two methine protons
and olefinic protons. The assignment of trans stereo-
chemistry to the â-lactams 3 was based on the observed
coupling constant of about 2.4 Hz for methine protons
H-3 and H-4.8
,10
In order to establish the synthetic potential of the
R-dienylazetidinones 3, we initiated Diels-Alder cycload-
dition reactions of 3 with dienophiles, viz. dimethylacety-
lene dicarboxylate (DMAD), maleic anhydride (MA),
N-phenylmaleimide (NPM), and 4-phenyl-1,2,4-triazo-
line-3,5-dione (PTAD). All these reactions resulted in
very good yields (92-97%) of the corresponding adducts
(
2) Page, M. I. Acc. Chem. Res. 1984, 17, 144.
(3) (a) Palomo, C.; Aizpurua, J . M.; Urchegui, R.; Iturburu, M.; de
Retana, A. O.; Cuevas, C. J . Org. Chem. 1991, 56, 2244. (b) Manhas,
M. S.; Ghosh, M.; Bose, A. K. J . Org. Chem. 1990, 55, 575. (c) van der
Veen, J . M.; Bari, S. S.; Krishnan, L.; Manhas, M. S.; Bose, A. K. J .
Org. Chem. 1989, 54, 5758. (d) Palomo, C.; Cossio, F. P.; Arrieta, A.;
Odriozola, J . M.; Oiarbide, M.; Ontoria, J . M. J . Org. Chem. 1989, 54,
5
736.
4) Arrastia, I.; Arrieta, A.; Ugalde, J . M.; Cossio, F. P.; Lecea, B.
Tetrahedron Lett. 1994, 35, 7825.
5) Bose, A. K.; Banik, B. K.; Manhas, M. S. Tetrahedron Lett. 1995,
6, 213 and references cited therein.
6) Georg, G. I., Ed. The Organic Chemistry of â-Lactams; VCH:
New York, 1992; Chapter 6 and references cited therein.
7) Bose, A. K.; Spiegelman, G.; Manhas, M. S. Tetrahedron Lett.
971, 3167.
8) Zamboni, R.; J ust, G. Can. J . Chem. 1979, 57, 1945.
(
(
3
(9) (a) Sharma, A. K.; Mahajan, M. P. Heterocycles 1995, 40. 787.
(b) Dey, P. D.; Sharma, A. K.; Rai, S. N.; Mahajan, M. P. Tetrahedron
1995, 51, 7459 and references cited therein.
(10) (a) Ren, X.-F.; Turos, E. J . Org. Chem. 1994, 59, 5858. (b) Ren,
X.-F.; Turos, E.; Lake, C. H.; Churchill, M. R. J . Org. Chem. 1995, 60,
6468.
(
(
1
(
S0022-3263(95)02249-3 CCC: $12.00 © 1996 American Chemical Society

Diastereoselective Synthesis of 3-Butadienylazetidinones
J . Org. Chem., Vol. 61, No. 16, 1996 5507
Sch em e 1
NPM in refluxing toluene yielded a mixture (2:1), as
1
13
evidenced by H and C NMR spectra, of diastereoiso-
mers 7/7′ and 8/8′, respectively (Scheme 3). Several
attempts at chromatographic separations of the two
diastereoisomers 7/7′ and 8/8′ failed because of the
similar R
these adducts by NMR is complicated. Although 7/7′ and
/8′ displayed spectroscopic parameters fully compatible
f
values. The assignment of stereochemistry of
8
with the gross structural features, NOE experiments
were inconclusive and their specific relative stereochem-
istry was not assigned.
In summary, the use of butadienylketene resulted in
a convenient method for the synthesis of 3-butadienyl
â-lactams and various R-substituted â-lactams. The
cycloadditions of butadienylketene with various imines
and heterodienes could, in fact, prove to be a general
method for the synthesis of various 1,3-butadiene-
substituted heterocyclic systems. The scope and utility
of these reactions are under active investigation in our
laboratories, and results will be reported in due course.
Sch em e 2
Exp er im en ta l Section
All melting points are uncorrected. 1H NMR (300 MHz) and
proton-decoupled 13C NMR (75.4 MHz) spectra were recorded
in CDCl solutions using TMS as internal standard. Mass
3
spectra were obtained by electron impact at 70 eV.
P r ep a r a tion of Sor byl Ch lor id e (2). Equivalent amounts
of sorbic acid (45 mmol, 5.0 g) and thionyl chloride (45 mmol,
5
.3 g, 3.3 mL) were refluxed in dry toluene (20 mL) for 2.5-3
h. The solvent was removed under reduced pressure, and the
sorbyl chloride thus obtained was further purified by distil-
lation under reduced pressure: yield 4.90 g (84%); bp (ob-
served 75 °C, 20 mm; lit.11 75 °C, 20 mm).
Gen er a l P r oced u r e for Azetid in on es 3. A solution of
sorbyl chloride (2) (3 mmol) in dry CH
dropwise to a solution of Schiff base 1 (2 mmol) and triethyl-
amine (6 mmol) in CH Cl under stirring at rt. After the
2 2
Cl (30 mL) was added
2
2
addition was complete (ca. 1.5 h), the solution was stirred for
an additional 15 min, washed with water (5 × 50 mL), and
dried over anhydrous sodium sulfate. The solvent was re-
moved under reduced pressure, and the crude product thus
obtained was further purified by column chromatography
(silica gel) using a solution of ethyl acetate and hexane (1:9)
as eluent.
t r a n s-3-(1′,3′-B u t a d ie n y l)-1,4-d ip h e n y la ze t id in -2-
on e (3a ): yield 59%; mp 118-119 °C; IR (KBr) ν 1734, 1596,
which were well characterized (elemental analysis, IR,
H NMR, C NMR, and mass spectral data). The
1
13
1496 cm-1
; H NMR δ 3.77 (dd, J ) 8.1 and 2.5 Hz, 1H), 4.80
1
(
1
)
7
6
d, J ) 2.5 Hz, 1H), 5.14 (d, J ) 9.8 Hz, with fine splitting,
reactions of 3 with DMAD in refluxing toluene resulted
in the exclusive isolation of the conjugated cyclohexadi-
enyl adducts 5 (Scheme 2). The products could be
assigned either structure 4 and 5 on the basis of IR, mass
spectra, and 13C and simple H NMR spectra. However,
the products were assigned structure 5 on the basis of a
H), 5.24 (d, J ) 16.2 Hz, with fine splitting, 1H), 5.88 (dd, J
14.3 and 8.1 Hz, with fine splitting, 1H), 6.30-6.39 (m, 2H),
13
.02-7.07 (m, 1H), and 7.21-7.38 (m, 9H); C NMR δ 61.7,
3.3, 117.1, 118.5, 124.0, 125.5, 125.8, 128.6, 129.1, 129.2,
1
+
135.5, 135.9, 137.2, 137.5, and 165.4; ms m/z 275 (M
(M - PhsNdCdO). Anal. Calcd for C19
), 156
+
H17NO: C, 82.88;
1
1
{
(
H}-{ H} NMR homonuclear spin correlation spectrum
H, 6.22; N, 5.08. Found: C, 82.83; H, 6.25; N, 5.15.
t r a n s-3-(1′,3′-B u t a d ie n y l)-4-(p -m e t h o x y p h e n y l)-1-
p h en yla zetid in -2-on e (3b): yield 63%; mp 104-105 °C; IR
Figure 1) which indicated that both methylene protons
were coupled to 1′H, which in turn was coupled with only
one of the olefinic protons. Further, the coupling con-
stants observed in the 300 MHZ 1H NMR spectrum
between the 1′H and the two methylene protons were ca.
-
1
1
(
4
CCl ) ν 1726, 1591, 1492 cm ; H NMR δ 3.71 (dd, J ) 8.0
and 1.7 Hz, 1H), 3.78 (s, 3H), 4.75 (d, J ) 1.7 Hz, 1H), 5.12 (d,
J ) 9.5 Hz, with fine splitting, 1H), 5.22 (d, J ) 16.0 Hz, with
fine splitting, 1H), 5.86 (dd, J ) 14.0 and 8.0 Hz, with fine
splitting, 1H), 6.25-6.41 (m, 2H), 6.90 (d, J ) 8.5 Hz, 2H),
7.00-7.05 (m, 1H), 7.17-7.35 (m, 6H); 13C NMR (one C
7
.0 and 5.0 Hz. Values such as these are only possible
when 1′H is adjacant to the methylene protons; such
large coupling constants between the two cannot be
anticipated on the basis of structure 4. The adducts 5
presumably arise from the rearrangement of the initially
formed nonconjugated 2′,5′-cyclohexadienyl Diels-Alder
adducts 4. The reaction of 3b with PTAD, in methylene
chloride at 0 °C, also resulted in the diastereoselective
synthesis of the corresponding Diels-Alder adduct 6
missing) δ 55.3, 61.3, 63.4, 114.5, 117.0, 118.4, 123.9, 125.6,
+
1
1
7
27.1, 129.0, 135.4, 135.9, 137.5, 159.7, 165.5; ms m/z 305 (M ),
+
2
86 (M - PhsNdCdO). Anal. Calcd for C20H19NO : C,
8.66; H, 6.27; N, 4.59. Found: C, 78.72; H, 6.23; N, 4.49.
t r a n s -3-(1′,3′-B u t a d i e n y l)-1-(p -m e t h y lp h e n y l)-4-
p h en yla zetid in -2-on e (3c): yield 59%; viscous oil; IR (KBr)
(11) MacMillan, J . H.; Washburne, S. S. J . Org. Chem. 1973, 38,
(Scheme 2). However, the reactions of 3a with MA and
2982.

5
508 J . Org. Chem., Vol. 61, No. 16, 1996
Sharma et al.
1
1
3
F igu r e 1. 300 MHz { H}-{ H} NMR homonuclear spin correlation (COSY) spectrum for 5a in CDCl .
+
+
Sch em e 3
ms m/z 289 (M ), 170 (M - PhsNdCdO). Anal. Calcd for
19NO: C, 83.01; H, 6.62; N, 4.84. Found: C, 83.12; H,
20
C H
6
.61; N, 4.76.
tr a n s-3-(1′,3′-Bu t a d ien yl)-4-(p -m et h oxyp h en yl)-1-(p -
m eth ylp h en yl)a zetid in -2-on e (3d ): yield 48%; viscous oil;
-
1
1
IR (CCl ) ν 1751, 1583, 1511 cm ; H NMR δ 2.22 (s, 3H),
4
3
.70 (dd, J ) 8.2 and 2.4 Hz, 1H), 3.74 (s, 3H), 4.71 (d, J ) 2.4
Hz, 1H), 5.10 (d, J ) 9.3 Hz, with fine splitting, 1H), 5.20 (d,
J ) 16.4 Hz, with fine splitting, 1H), 5.84 (dd, J ) 14.1 and
8
)
7
.2 Hz, with fine splitting, 1H), 6.23-6.40 (m, 2H), 6.87 (d, J
8.7 Hz, with fine splitting, 2H), 7.01 (d, J ) 8.3 Hz, 2H),
.19 (d, J ) 8.3 Hz, with fine splitting, 2H), 7.24 (d, J ) 8.7
1
3
Hz, with fine splitting, 2H); C NMR δ 20.8, 55.2, 61.2, 63.3,
1
1
3
NO
4
14.5, 117.0, 118.3, 124.2, 125.8, 127.1, 128.2, 129.1, 129.4,
29.6, 133.4, 135.2, 135.8, 135.9, 136.1, 159.7, 165.2; ms m/z
+
+
19 (M ), 200 (M - PhsNdCdO). Anal. Calcd for C21
: C, 78.97; H, 6.63; N, 4.39. Found: C, 78.93; H, 6.59; N,
.31.
Gen er al P r ocedu r e for Diels-Alder Addu cts 5. Equiva-
21
H -
2
ν 1739, 1493, 1498 cm-1; 1H NMR δ 2.25 (s, 3H), 3.72 (dd, J )
8
.1 and 2.4 Hz, 1H), 4.76 (d, J ) 2.4 Hz, 1H), 5.11 (d, J ) 10.0
lent amounts of â-lactam 3 and DMAD were refluxed in dry
toluene for 6-7 h. The solvent was removed under reduced
pressure, and the crude product was purified by recrystalli-
zation from a benzene:hexane (3:1) mixture.
tr a n s-3-[2′,3′-Bis(m eth oxyca r bon yl)-2′,4′-cycloh exa d i-
en yl]-4-(p-m eth oxyp h en yl)-1-p h en yla zetid in -2-on e (5a ):
yield 95%; mp 178-179 °C; IR (KBr) ν 1733, 1715, 1597, 1497
Hz, with fine splitting, 1H), 5.22 (d, J ) 16.3 Hz, with fine
splitting, 1H), 5.84 (dd, J ) 14.2 and 8.1 Hz, with fine splitting,
1
2
H), 6.23-6.39 (m, 2H), 7.01 (d, J ) 8.2 Hz, with fine splitting,
H), 7.19 (d, J ) 8.2 Hz, with fine splitting, 2H), 7.27-7.39
1
3
(m, 5H); C NMR δ 20.9, 61.6, 63.2, 117.0, 118.5, 125.8, 126.9,
1
28.8, 129.3, 129.7, 133.6, 135.0, 135.5, 135.9, 137.2, 165.2;

Diastereoselective Synthesis of 3-Butadienylazetidinones
J . Org. Chem., Vol. 61, No. 16, 1996 5509
cm- ; H NMR δ 2.98 (ddd, J ) 23.3, 4.9, and 4.9 Hz, 1H),
1
1
1596, 1497 cm-1; 1H NMR (mixture of diastereoisomers is 2:1
ratio) δ 2.21-2.30 (m, 2H, both isomers), 2.70-2.90 (m, 4H,
both isomers), 3.45-3.57 (m, 3H, two for minor isomer and
one for major isomer), 3.84 (dd, J ) 11.4 and 2.4 Hz, 1H, minor
isomer), 3.92 (dd, J ) 12.0 and 2.4 Hz, 1H, major isomer), 4.01
(dd, J ) 9.8 and 5.8 Hz, 1H, major isomer), 4.72 (d, J ) 2.4
Hz, 1H, major isomer), 4.83 (d, J ) 2.4 Hz, 1H, minor isomer),
5.85 (ddd, J ) 9.3, 3.2 and 3.2 Hz, 1H, major isomer), 6.03-
6.13 (m, 2H, both isomers), 6.29 (ddd, J ) 9.4, 3.2, and 3.2
Hz, 1H, minor isomer), 7.01-7.07 (m, 2H, both isomers) 7.22-
7.28 (m, 8H, both isomers), 7.34-7.40 (m, 10H, both isomers);
3
4
3
1
.19 (dddd, J ) 23.3, 6.9, 4.6, and 2.2 Hz, 1H), 3.26 (dd, J )
.7 and 2.6 Hz, 1H), 3.63 (s, 3H), 3.75 (s, 3H), 3.77 (s, 3H),
.87 (m, 1H), 4.81 (d, J ) 2.3 Hz, 1H), 5.82 (m, 1H), 5.91 (m,
H), 6.86 (d, J ) 8.4 Hz, 2H), 6.98-7.03 (m, 1H), 7.18-7.26
m, 6H); C NMR δ 27.8, 36.4, 52.3, 52.4, 55.2, 57.6, 63.6,
14.5, 117.0, 123.8, 124.3, 125.1, 127.3, 128.9, 129.4, 134.2,
34.7, 137.4, 159.7, 164.9, 167.4, 168.2; ms m/z 447 (M ), 328
M - PhsNdCdO). Anal. Calcd for C26
.63; N, 3.13. Found: C, 69.65; H, 5.64; N, 3.19.
1
3
(
1
1
(
+
+
H
25NO
6
: C, 69.79; H,
5
tr a n s-3-[2′,3′-Bis(m eth oxyca r bon yl)-2′,4′-cycloh exa d i-
1
3
en yl]-1-(p -m et h ylp h en yl)-4-p h en yla zet id in -2-on e (5b ):
yield 97%; mp 182-182.5 °C; IR (KBr) ν 1719, 1506, 1431,
C NMR (mixture of diastereoisomers in 2:1 ratio) δ 24.2, 35.6,
40.2, 42.7, 59.3, 60.1 (minor isomer); 24.7, 36.4, 40.5, 42.9, 59.1,
61.1 (major isomer); 117.0, 124.1, 124.2, 126.1, 126.2, 128.6,
128.8, 128.9, 129.1, 129.2, 129.4, 129.8, 130.4, 130.6, 136.7,
137.0, 137.2, 137.3, 165.9 (both isomers), 171.1, 173.7 (minor
-
1 1
1
5
383, 1253 cm ; H NMR δ 2.25 (s, 3H), 2.98 (ddd, J ) 23.3,
.3, and 4.6 Hz, 1H), 3.21 (dddd, J ) 23.3, 7.0, 5.0, and 2.5
Hz, 1H), 3.27 (dd, J ) 4.6 and 2.6 Hz, 1H), 3.64 (s, 3H), 3.76
+
(
s, 3H), 3.85-3.91 (m, 1H), 4.83 (d, J ) 2.3 Hz, 1H), 5.81 (m,
isomers); 171.7, 174.0 (major isomer); ms m/z 373 (M ), 254
+
1
H), 5.91 (m, 1H), 7.02 (d, J ) 8.3, 2H), 7.20 (d, J ) 8.4, with
(M - PhsNdCdO).
1
3
fine splitting, 2H), 7.25-7.36 (m, 5H); C NMR (two C
missing) δ 20.8, 27.8, 36.4, 52.3, 52.4, 57.8, 63.5, 116.9, 124.3,
Diels-Ald er Ad d u ct of 3a a n d N-P h en ylm a leim id e (8/
8′). A solution of 3a (0.30 g, 1.10 mmol) and N-phenylmale-
imide (0.19 g, 1.12 mmol) in toluene (4 mL) was refluxed for
2h. The reaction mixture was then purified by chromatogra-
phy on 60-120 mesh silica gel column (eluent: mixture of
AcOEt/hexane in 1:3 ratio), affording a colorless solid consist-
ing in a mixutre of diastereoisomers in a 2:1 ratio (0.45 g,
92%): IR (KBr, mixture of diastereoisomers in a 2:1 ratio) ν
1
25.2, 126.0, 128.4, 129.0, 129.5, 133.4, 134.9, 137.6, 164.5;
ms m/z 431 (M ), 312 (M - PhsNdCdO). Anal. Calcd for
26 5
C H25NO
+
+
: C, 72.38; H, 5.84, N, 3.25. Found: C, 72.30, H,
5
.91; N, 3.29.
tr a n s-4-(p -Met h oxyp h en yl)-1-p h en yl-7′,9′-d ioxo-3-[8′-
p h en yl-1′,6′,8′-t r ia za [4.3.0]b icyclon on -3′-en -yl]a zet id in -
-on e (6). To a stirred solution of PTAD (0.58 g, 3.3 mmol)
-
1
1
2
1727, 1702, 1591, 1492, 1379 cm ; H NMR (mixture of
in methylene chloride (25 mL) at 0 °C was added 3b (1 g, 3.3
mmol) in portions over a period of 5 min. The solution was
stirred at 0 °C for an additional 10 min. The crude product
obtained after removal of the solvent was purified by column
chromatography (silica gel, 60-120 mesh) using a solution of
ethyl acetate and hexane (1:3) to yield 1.46 g (92%) of adduct
diastereoisomers in 2:1 ratio) δ 2.25-2.31 (m, 2H, both
isomers); 2.83-2.94 (m, 4H, both isomers); 3.30-3.41 (m, 3H,
two for minor isomer and one for major isomer); 3.91 (dd, J )
8.9 and 5.6 Hz, 1H, major isomer); 4.07 (dd, J ) 10.9 and 2.1
Hz, 1H, minor isomer); 4.17 (dd, J ) 12.1 and 2.1 Hz, 1H,
major isomer), 4.72 (d, J ) 2.1 Hz, 1H, major isomer); 4.86 (d,
J ) 2.1 Hz, 1H, minor isomer), 5.85 (ddd, J ) 9.1, 3.2, and 3.2
Hz, 1H, major isomer), 6.06-6.12 (m, 2H, both isomers), 6.30
(ddd, J ) 9.3, 3.2 and 3.2 Hz, 1H, minor isomer), 7.01-7.05
(m, 2H, both isomers); 7.16 (d, J ) 7.3 Hz, with fine splitting,
-
1
6
: mp 200-202 °C; IR (KBr) ν 1744, 1708, 1595, 1493 cm
;
1
H NMR δ 3.47 (dd, J ) 10.3 and 2.3 Hz, 1H), 3.76 (s, 3H),
3
1
6
.97 (dq, J ) 16.7 and 2.4 Hz, 1H), 4.30 (dddd, J ) 16.7, 4.2,
.9, and 0.8 Hz, 1H) 5.11 (m, 1H), 5.46 (d, J ) 2.3 Hz, 1H),
.04 (dddd, J ) 10.3, 4.0, 2.0, and 2.0 Hz, 1H), 6.42 (dddd, J
1
3
4H, both isomers), 7.19-7.41 (m, 24H, both isomers); C NMR
(mixture of diastereoisomers in a 2:1 ratio) δ 24.5, 36.8, 39.8,
42.0, 59.6, 60.6 (minor isomer); 25.1, 37.3, 40.0, 42.0, 59.7, 61.4,
(major isomer); 117.0, 124.0, 126.1, 126.3, 126.4, 126.5, 128.6,
128.7, 129.0, 129.1, 129.3, 129.5, 130.0, 130.5, 131.7, 137.4,
137.5 (both isomers); 166.5, 176.0, 178.4 (minor isomer); 166.6,
)
10.3, 4.8, 2.4, and 2.4 Hz, 1H), 6.74 (d, J ) 8.7 Hz, with fine
splitting, 2H), 7.00-7.06 (m, 1H), 7.18-7.31 (m, 8H), 7.39-
1
3
7
1
1
.52 (m, 3H); C NMR δ 44.5, 52.9, 55.3, 58.7, 63.7, 114.5,
17.2, 121.7, 123.6, 124.2, 125.9, 127.6, 128.5, 129.1, 129.2,
+
30.7, 137.1, 151.6, 153.6, 159.8, 163.2; ms m/z 480 (M ), 361
+
+
+
(M
- PhsNdCdO). Anal. Calcd for C28
H
24
N
4
O
4
: C, 69.99;
176.7, 178.6 (major isomer); ms m/z 448 (M ), 329 (M
PhsNdCdO).
-
H, 5.03; N, 11.66. Found: C, 70.11; H, 5.09; N, 11.59.
Diels-Ald er Ad d u ct of 3a a n d Ma leic An h yd r id e (7/
7
(
′). A solution of 3a (0.30 g, 1.10 mmol) and maleic anhydride
Ackn owledgm en t. The authors thank RSIC, NEHU,
Shillong, for analytical and spectral data and UGC New
Delhi for financial assistance under a Special Assistance
Program. A.K.S. thanks CSIR, New Delhi, for a Senior
Research Fellowship.
0.11 g, 1.11 mmol) in toluene (4 mL) was refluxed for 1 h.
The reaction mixture was then purified by chromatography
on a 60-120 mesh silica gel column (eluent: mixture of AcOEt/
hexane in a 1:4 ratio), affording a colorless solid consisting in
a mixture of diastereoisomers in 2:1 ratio (0.38 g, 93%): IR
(KBr, mixture of diastereoisomers in 2:1 ratio) ν 1770, 1739,
J O952249I