Notes
J . Org. Chem., Vol. 61, No. 14, 1996 4819
evaporated to give colorless oil which solidified upon standing
to give palasonin (3,96 g, 21.8 mmol) in 99% yield. The solid
obtained was recrystallized from CH2Cl2/n-pentane to give
colorless crystals of palasonin (3.59 g, 19.7 mmol) in 90% yield:
mp 85-86 °C; IR νmax 1791, 1850, 2885, 2941, 2979, 3000, 3021
2H), 6.66 (s, 2H); 13C NMR δ 38.3, 74.9, 83.6, 137.0, 170.3]. 1H
NMR values of 9 and 10 are in agreement with those reported.13b
Solvolysis of 7 in 5.0 M LiClO4/Et2O a n d 4.4 M F u r a n .
A solution of 7 (0.1076 g, 0.6 mmol, 0.3 M), furan (0.6 g, 8.8
mmol), LiClO4 (1.1 g, 5.0 M), and Et2O (2 mL) was stirred at 20
°C for 48 h. The reaction was quenched with water. and the
mixture was extracted with chloroform. The organic extract was
dried (MgSO4) and evaporated to give a brown oil (0.04 g, 60%
yield): 1H NMR (6, δ 2.19; 7, δ 1.33) showed 6:7 in a ratio of
97:3.
1
cm-1; H NMR5,6,9 δ 1.44 (s, 3H), 1.55-1.63 (m, 1H), 1.73-1.83
(m, 1H), 1.87-1.98 (m, 2H), 2.66 (s, 3H), 4.79 (d, J ) 5.1 Hz,
1H), 4.92 (d, J ) 5.3 Hz, 1H); 13C NMR δ 16.2, 23.7, 28.2, 54.9,
56.4, 81.4, 83.3, 171.0, 175.6; exact mass calcd for C9H10O4
182.0591, found 182.0576. Anal. Calcd for C9H10O4: C, 59.34;
H, 5.53. Found: C, 59.22; H, 5.74.
(-)-P a la son in a n d (+)-P a la son in . 1,3-Dicyclohexylcarbo-
diimide (DCC) (3.62 g, 17.6 mmol) in THF (10 mL) was added,
dropwise, to a stirred solution of (()-palasonin (3.2 g, 17.6 mmol),
(S)-(-)-R-methylbenzylamine (2.2 g, 18.0 mmol), Et3N (1.8 g, 18.0
mmol), and THF (200 mL), and the solution was stirred for 18
h. A second equiv of (S)-(-)-R-methylbenzylamine (2.2 g, 18
mmol) was added to the solution. The reaction mixture was
filtered, and the filtrate was concentrated to a small volume (20
mL) and stirred at rt for 48 h. Hexane/EtOAc (7/3) was added
to the reaction mixture, and the mixture was filtered. The
crystals collected were (S)-(-)-R-methylbenzyl-2-methylendo-
Solvolysis of 9 in 5.0 M LiClO4/Et2O a n d 2.2 M F u r a n .
A solution of 9 (0.0521 g, 0.33 mmol, 0.17 M), furan (0.3 g, 4.4
mmol), LiClO4 (1.1 g, 5.0 M), and Et2O (2 mL) was stirred at 20
°C for 15 h. The reaction was quenched with water, and the
mixture was extracted with chloroform. The organic extract was
dried (MgSO4) and evaporated to give a pale yellow solid: 1H
NMR (8, δ 4.00; 9, δ 5.20) showed 8:9 in a ratio of 47:3.
Gen er a l P r oced u r es for Kin etics. At Nor m a l P r essu r e.
A solution of reactants was stirred at the specified temperature
with the reaction followed by taking an aliquot at time T for 1H
NMR analysis. The relative quantities of [7] and [6] were
determined by 1H NMR intergrals: 7, δ 1.32; 6, δ 2.18. With
Gr ieco Rea gen t. A solution of reactants was stirred in 2 mL
of 5.0 M LiClO4 in Et2O at 20 °C. The reaction was quenched
at time T with water, and the solution was extracted with CHCl3.
The organic extract was dried (MgSO4) and evaporated. The
reaction was followed until the equilibrium state was attained.
The relative quantities of [7] and [6] were determined by 1H
NMR intergrals: 7, δ 1.32; 6, δ 2.18.
thalldiamide (2.86 g, 40%): mp 195 °C; [R]20 -83.9° (c 0.6,
D
CHCl3). The filtrate was concentrated and was chromato-
graphed with EtOAc to give the other isomer (S)-(-)-R-methyl-
benzyl-2-methylendothalldiamide (3.10 g, 43%): [R]20 -78.5°
D
(c 0.7, CHCl3). Each diamide (2.5 g, 6.2 mmol) was saponified
in refluxing aqueous NaOH/EtOH (50 mL, 2.5 M) for 18 h and
the solution was neutralized by adding hydrochloric acid. The
solution was evaporated, and the residue was chromatographed
through a cation exchange resin column with MeOH/H2O (1:1).
The elutant was evaporated, MeOH was added to the residue,
and the mixture was filtered. The filtrate was evaporated to
give the diacid which was refluxed in SOCl2 for 1.5 h. Unreacted
SOCl2 was removed under reduced pressure. Hexane/EtOAc (3/
2) was added to the brown residue, and the solution was filtered.
The filtrate was concentrated to give the corresponding palaso-
The amount of 7 left unreacted was calculated by the equation
[7]/{[7] + [6]} × 100%. A plot of ln [7] versus time (up to 75%
conversion of 7) gave a straight line. The slope obtained gave
the first-order rate constant k-1
. The half-life was calculated
from the equation, t1/2 ) ln 2/k-1
.
1
nin (0.73 g, 65%) and H NMR showed greater than 95% purity.
Kin etics. Retr o Diels-Ald er Rea ction s u n d er Nor m a l
Con d ition . The initial concentration of 7 was 5.1 × 10-1 M at
both 20 and 40 °C in THF (0.5 mL) and furan (1.6 mL). Diels-
Ald er Rea ction s u n d er Nor m a l Con d ition . The initial
concentration of 6 was 6.9 × 10-1 M in furan (10.7 mL) at 20 °C
and 6 was 1.4 M in furan (5.3 mL) at 40 °C. The equilibrium
constant K (k1/k-1) was calculated from the equation k1[6][furan]
) k-1[7] where [furan] ) 13.75 M. At 20 °C, [7]/[6] ) 0.015 and
K ) 1.1 × 10-3 M-1; at 40 °C, [7]/[6] ) 0.011 and K ) 8 × 10-4
M-1. Retr o Diels-Ald er Rea ction s in Gr ieco Rea gen t. The
initial concentration of 7 was 2.8 × 10-1 M. Diels-Ald er
Rea ction s in Gr ieco Rea gen t. (a) The initial concentration
of 6 was 4.5 × 10-1 M and furan was 4.41 M. The equilibrium
constant K (k1/k-1) was calculated from the equation k1[6][furan]
) k-1[7]: at equilibrium, [7]/[6] ) 0.044 and [furan] > [6] > [7],
i.e., k1/k-1 ) 1.0 × 10-2 M-1 and k1 ) 4.4 × 10-7 M-1 s-1 (see
Figure 1). (b) The initial concentration of 2,5-dihydrothiophene-
3,4-dicarboxylic acid anhydride (8) was 2.0 × 10-1 M and furan
was 2.2 M in 2 mL of 5.0 M LiClO4 at 20 °C. At equilibrium,
A sample was chromatographed with hexane/EtOAc (3/2) and
crystallized out in cold ether/hexane. (-)-Palasonin [mp 104-
105 °C; [R]20D -2.3° (c 0.2, CHCl3)] and (+)-palasonin [mp 105-
106 °C; [R]20 +2.2° (c 0.3, CHCl3)]. Their spectral data were
D
identical to those of (()-palasonin.
Stoich iom etr ic Stu d ies of Cycloa d d ition of Citr a con ic
An h yd r id e (6) w ith F u r a n . (a) A solution of 6 (0.22 g, 1.9
mmol), and furan (1.31g, 19 mmol) was pressurized to 8 kbar
for 64 h. The reaction mixture was evaporated under reduced
pressure to give a white solid, and the 1H NMR spectrum
indicated the presence of 7:4:5 in a ratio of 16:57:27. The
mixture was chromatographed (EtOAc/hexane: 3/2) to give (i)
4 [mp 205-206 °C (EtOAc/hexane); IR νmax 1799, 1858, 2979,
1
3016 cm-1; H NMR δ 1.49 (s, 3H), 2.58 (dd, 1H), 2.61 (s, 3H),
2.83 (dd, 1H), 4.38 (s, 1H), 4.47 (s, 1H), 4.96 (s, 1H), 4.98 (s,
1H), 6.29 (dd, 1H); 13C NMR δ 15.1, 42.9, 47.6, 57.2, 79.1, 79.3,
79.5, 80.5, 133.4, 134.1, 170.2, 174.8; exact mass calcd for
C
13H12O5 248.0685, found 248.0680] and (ii) 5 [1H NMR δ 1.46
(s, 3H), 2.01 (d, 1H), 2.20 (d, 1H), 2.66 (s, 1H), 4.76 (s, 1H), 4.88
(s, 1H), 4.98 (s, 1H), 6.41 (dd, 1H), 6.44 (dd, 1H); 13C NMR δ
15.6, 42.4, 47.9, 56.5, 56.6, 80.5, 80.6, 83.1, 84.3, 137.0, 137.6,
170.4, 174.8; exact mass calcd for C13H12O5 248.0685, found
248.0680]. (b) A solution of 6 (1.17g, 10.5 mmol) and furan (0.75
g, 11.0 mmol) was pressurized to 8 kbar for 138 h. The reaction
mixture was evaporated under reduced pressure to give a white
solid, and the 1H NMR spectrum showed a 99% conversion of
the substrates to 7:4:5 in a ratio of 98:1:1.
{[9] + [10]}/[8] ) 7.1, i.e., k1/k-1 ) 3.0 M-1
.
Ack n ow led gm en t. This research was supported by
National Science Foundation Grant 8618303. We thank
Professor J . E. Casida and Dr. N. Kawamura for their
advice and encouragement.
Cycloa d d ition of 2,5-Dih yd r oth iop h en e-3,4-d ica r boxylic
Acid An h yd r id e (8) w ith F u r a n . A solution of 8 (0.12 g, 0.79
mmol), furan (0.17 g, 2.5 mmol), and CH2Cl2 (0.5 mL) was
pressurized to 7.5 kbar for 24 h. The reaction mixture was
extracted with CHCl3 and evaporated in vacuo to give a pale
brown solid: 1H NMR showed 8:9:10 in a ratio of 2:6:1. The
mixture was chromatographed (EtOAc/hexane: 2/3) to give (i)
the exo isomer 9 (0.09 g, 0.4 mmol) in 50% yield [Rf 0.43; 1H
NMR δ 2.69, 3.14 (AB quartet, J ) 12.6 Hz, 4H), 5.18, (s, 2H),
6.74 (s, 2H); 13C NMR δ 35.6, 76.6, 83.7, 138.0, 173.0] and (ii)
the endo isomer 10 (0.0127g, 0.06 mmol) in 7% yield [Rf 0.57;
1H NMR δ 3.11, 3.48 (AB quartet, J ) 12.7 Hz, 4H), 5.03 (s,
Su p p or t in g In for m a t ion Ava ila b le: 1H NMR and 13C
NMR spectra of two diastereomeric (S)-(-)-R-methylbenzyl-
2-methylendothalldiamides and a table of the correlation of
molar equiv of furan and the yield of compounds 7, 4, and 5
(5 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.
J O960210N