Mu¨nchnone-Alkene Cycloadditions
J . Org. Chem., Vol. 61, No. 21, 1996 7297
angles, and dihedral angles). Stationary points on the poten-
tial energy surfaces were characterized according to the
number of negative vibrational frequencies.34 With the opti-
mized geometries at the PM3 level, the energy determination
was made using a single point restricted second-order Møller-
Plesset (RMP2) perturbation calculation with frozen core (FC)
approximation using the 6-31G basis set of Pople.30 The ab
initio calculations were performed using the GAUSSIAN 92
system of programs.36
portions of methanol, which was evaporated under reduced
pressure, and the aqueous solution was extracted with 1:1
ethyl acetate-diethyl ether (3 × 50 mL). The organic extracts
were dried and evaporated to give a residue that crystallized
from ethyl acetate (0.35 g, 66%): mp 168-170 °C; [R]D -67°
(c 0.5, C5H5N); λmax (96% EtOH) 276, 397 nm (ꢀmM 15.3, 10.9);
1
νmax 3360 (OH), 1590, 1510 (CdC) cm-1; H NMR (DMSO-d6/
D2O) δ 8.31 (d, 2H, 4-nitrophenyl), 7.80 (d, 2H, 4-nitrophenyl),
7.51 (m, 5H, phenyl), 6.67 (s, 1H, H-4), 4.76 (s, 1H, J 1′,2′ ) 0
Hz, H-1′), 3.77-3.41 (m, 5H, H-2′, H-3′, H-4′, H-5′, H-5′′), 3.50
(s, 3H, NCH3): 13C NMR (DMSO-d6/D2O) δ 145.6, 138.7, 136.4,
132.7, 131.1, 130.8, 128.6, 128.2, 127.0, 132.4 (aryl), 109.6 (C-
4), 73.9 (C-2′), 70.1 (C-4′), 69.8 (C-3′), 64.5 (C-1′), 63.1 (C-5′),
34.1 (NCH3). Anal. Calcd for C22H24N2O7: C, 61.67; H, 5.65;
N, 6.54. Found: C, 61.50; H, 5.72; N, 6.29.
3-(P en ta -O-a cetyl-D-ga la cto-p en titol-1-yl)-1-m eth yl-2-
(4-n itr op h en yl)-5-p h en ylp yr r ole (5). P r oced u r e A.
A
suspension of 1 (1.18 g, 4.0 mmol) and 2 (0.87 g, 2.0 mmol) in
toluene (50 mL) was refluxed for 3 h. The solvent was
evaporated under reduced pressure to give an oily residue that
crystallized from ethanol (0.89 g, 69%): mp 150-152 °C; [R]D
-78° (c 0.5, CHCl3); λmax (96% EtOH) 227, 269, 382 nm (ꢀmM
1
10.2, 14.1, 8.1); νmax 1740 (CdO), 1590, 1510 (CdC) cm-1; H
1-Meth yl-2-(4-n itr op h en yl)-3-(D-m a n n o-p en titol-1-yl)-
5-p h en ylp yr r ole (8). A solution of 6 (0.45 g, 0.7 mmol) in
methanol (5 mL) was treated with 1 M sodium methoxide
solution (2 mL). After 15 min at room temperature, water (5
mL) and Amberlite IR-120 were added until neutral pH. The
Amberlite was filtered off and washed with methanol. The
solution was evaporated to dryness and the resulting oil
crystallized from diethyl ether (0.22 g, 73%): mp 98-100 °C
dec; [R]D -53° (c 0.5, C5H5N); λmax (96% EtOH) 232, 278, 399
nm (ꢀmM 11.4, 15.0, 11.2); νmax 3360 (OH), 1595, 1510 (CdC)
NMR (CDCl3) δ 8.36 (d, 2H, 4-nitrophenyl), 7.60 (d, 2H,
4-nitrophenyl), 7.39 (m, 5H, phenyl), 6.31 (s, 1H, H-4), 5.91
(d, 1H, J 1′,2′ ) 4.2 Hz, H-1′), 5.39 (dd, 1H, J 3′,4′ ) 3.0 Hz, H-3′),
5.19 (dd, 1H, J 2′,3′ ) 8.2 Hz, H-2′), 5.10 (m, 1H, J 4′,5′ ) 4.5 Hz,
J 4′,5′′ ) 7.0 Hz, H-4′), 4.20 (dd, 1H, J 5′,5′′ ) 11.8 Hz, H-5′), 3.85
(dd, 1H, H-5′′), 3.43 (s, 3H, NCH3), 2.09, 1.99, 1.88 (s, 15H,
CH3CO); 13C NMR (CDCl3) δ 170.5, 170.3, 170.2, 169.5
(CH3CO), 147.1, 138.4, 137.5, 132.4, 131.2, 128.9, 128.6, 127.7,
123.8, 117.6 (aryl), 108.2 (C-4), 71.0 (C-2′), 68.7 (C-3′), 68.0
(C-4′), 67.5 (C-1′), 62.1 (C-5′), 21.0, 20.8, 20.7, 20.6, 20.3
(CH3CO). Anal. Calcd for C32H34N2O12: C, 60.18; H, 5.37; N,
4.39. Found: C, 60.06; H, 5.39; N, 4.12.
1
cm-1; H NMR (DMSO-d6/D2O) δ 8.30 (d, 2H, 4-nitrophenyl),
7.88 (d, 2H, 4-nitrophenyl), 7.45 (m, 5H, phenyl), 6.42 (s, 1H,
H-4), 4.84 (s, 1H, J 1′,2′ ) 5.3 Hz, H-1′), 3.91-3.31 (m, 5H, H-2′,
H-3′, H-4′, H-5′, H-5′′), 3.40 (s, 3H, NCH3); 13C NMR (DMSO-
d6/D2O) δ 145.6, 138.8, 136.6, 132.7, 132.3, 130.9, 128.6, 128.2,
127.6, 127.0, 123.2 (aryl), 108.0 (C-4), 72.2 (C-2′), 71.6 (C-4′),
69.8 (C-3′), 64.3 (C-1′), 63.8 (C-5′), 34.1 (NCH3). Anal. Calcd
for C22H24N2O7: C, 61.67; H, 5.65; N, 6.54. Found: C, 61.73;
H, 5.47; N, 6.43.
P r oced u r e B. A suspension of 1 (1.36 g, 4.6 mmol) and 2
(1.00 g, 2.3 mmol) in acetic anhydride (15 mL) was stirred at
room temperature for 7 days. The reaction mixture was
poured into ice-water, and the resulting oil was extracted with
dichloromethane (10 mL), washed successively with sodium
hydrogencarbonate saturated solution (3 × 5 mL) and water
(3 × 5 mL), and dried. The solvent was evaporated and the
residue crystallized from ethanol (1.02 g, 69%).
3-F o r m y l -1 -m e t h y l -2 -(4 -n i t r o p h e n y l )-5 -p h e n y l -
p yr r ole (9). To a suspension of 7 (0.1 g, 0.23 mmol) in water
(10 mL) was added a solution of sodium metaperiodate (0.43
g, 2.0 mmol) in water (2 mL), and the reaction mixture was
stirred vigorously at room temperature. Within a few minutes,
the title compound crystallized as a yellow solid (0.07 g,
99%): mp 148-149 °C; λmax (CHCl3) 264, 370 nm (ꢀmM 22.3,
3-(P en t a -O-a cet yl-D-m a n n o-p en t it ol-1-yl)-1-m et h yl-2-
(4-n itr op h en yl)-5-p h en ylp yr r ole (6). A suspension of 1
(1.36 g, 4.6 mmol) and 3 (1.00 g, 2.3 mmol) in acetic anhydride
(15 mL) was stirred at room temperature for 7 days. Then,
the reaction mixture was poured into ice-water to give a
yellow solid. The product was purified by flash chromatog-
raphy (benzene-hexane-ethyl acetate, 4:4:1) and crystallized
from ethanol (0.96 g, 65 %): mp 84-86 °C; [R]D +53° (c 0.5,
CHCl3); λmax (96% EtOH) 227, 270, 383 nm (ꢀmM 5.8, 8.4, 5.1);
8.9); νmax 1660 (CdO), 1595, 1510 (CdC) cm-1 1H NMR
;
(CDCl3) δ 9.62 (s, 1H, CHO), 8.38 (d, 2H, 4-nitrophenyl), 7.68
(d, 2H, 4-nitrophenyl), 7.46 (m, 5H, phenyl), 6.81 (s, 1H, H-4),
3.53 (s, 3H, NCH3); 13C NMR (CDCl3) δ 185.6 (CHO), 147.8,
140.5, 138.3, 138.1, 131.6, 131.3, 129.1, 128.7, 128.3, 128.2,
124.2, 123.7 (aryl), 108.0 (C-4), 33.8 (NCH3). Anal. Calcd for
C18H14N2O3: C, 70.58; H, 4.61; N, 9.15. Found: C, 70.21; H,
4.60; N, 8.87.
1
νmax 1740 (CdO), 1590, 1510 (CdC) cm-1; H NMR (CDCl3) δ
8.34 (d, 2H, 4-nitrophenyl), 7.69 (d, 2H, 4-nitrophenyl), 7.39
(m, 5H, phenyl), 6.41 (s, 1H, H-4), 5.69 (d, 1H, J 1′,2′ ) 9.0 Hz,
H-1′), 5.56 (dd, 1H, J 2′,3′ ) 2.0 Hz, H-2′), 5.53 (dd, 1H, J 3′,4′
)
9.0 Hz, H-3′), 5.08 (m, 1H, J 4′,5′ ) 3.5 Hz, J 4′,5′′ ) 5.0 Hz, H-4′),
4.23 (dd, 1H, J 5′,5′′ ) 12.0 Hz, H-5′), 4.02 (dd, 1H, H-5′′), 3.43
(s, 3H, N-CH3), 2.03, 2.00, 1.98, 1.96, 1.88 (s, 15H, CH3CO);
13C NMR (CDCl3) δ 170.4, 169.8, 169.7, 169.4, 168.9 (CH3CO),
146.9, 138.4, 137.4, 133.0, 132.3, 130.9, 128.8, 128.4, 127.4,
123.6, 118.0 (aryl), 108.7 (C-4), 70.3 (C-2′), 67.9 (C-4′), 67.6
(C-3′), 66.3 (C-1′), 61.8 (C-5′), 33.9 (NCH3) 20.9, 20.8, 20.5
(CH3CO). Anal. Calcd for C32H34N2O12: C, 60.18; H, 5.37; N,
4.39. Found: C, 60.26; H, 5.34; N, 4.69.
Ack n ow led gm en t. We wish to thank the Spanish
Direccio´n de Investigacio´n Cient´ıfica y Te´cnica for
support through Grant Nos. PB92-0525-C02-01 and
PB90-930. This work was also supported by the J unta
de Extremadura and the Fondo Social Europeo under
award No. EIA94-32. We thank Prof. D. G. Truhlar for
kindly providing us the MORATE program. One of us
(J .C.C.) thanks J unta de Extremadura for a scholarship.
1-Meth yl-2-(4-n itr op h en yl)-3-(D-ga la cto-p en titol-1-yl)-
5-p h en ylp yr r ole (7). A solution of 5 (1.5 g, 2.35 mmol) in
methanol (30 mL) was treated with 1 M sodium methoxide
solution (15 mL). After 15 min at room temperature, water
(50 mL) and Amberlite IR-120 were added until neutral pH.
The Amberlite was filtered off and washed with additional
Su p p or tin g In for m a tion Ava ila ble: Geometrical param-
eters, formal charge distributions, enthalpies of formation, and
the ionization potentials for reactants, cycloadducts, and
saddle points, as well as calculation of Coulombic contributions
and MP2 energies and coefficients (4 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
(35) According to the nonconventional theories of the transition
state, a saddle point may not be coincidental with the transition state
since the former concept constitutes a more precise refinement over
the conventional approach. In the context of this work, however, the
readership should consider the concepts of saddle point and transition
state as equivalents.
(36) Frisch, M. J .; Head-Gordon, M.; Trucks, G. W.; Foresman, J .
B.; Schlegel, H. B.; Raghavachari, K.; Robb, M. A.; Binkley, J . S.;
Gonza´lez, C.; DeFrees, D. J .; Fox, D. J .; Whiteside, R. A.; Seeger, R.;
Melius, C. F.; Baker, J .; Martin, R. L.; Kahn, L. R.; Stewart, J . J . P.;
Topiol, S.; Pople, J . A. GAUSSIAN 92, Gaussian, Inc., Pittsburgh, 1992.
J O960483I