Optically Active Axially Chiral Anilide and Maleimide Derivatives
J . Org. Chem., Vol. 63, No. 8, 1998 2639
5.47 (1H, dd, J ) 2.1, 10.3 Hz), 5.90 (1H, dd, J ) 10.3, 16.8
Hz), 6.03 (1H, dddd, J ) 5.1, 8.1, 9.9, 17.1 Hz), 6.37 (1H, dd,
J ) 2.1, 16.8 Hz), 6.94 (1H, dd, J ) 1.5, 7.8 Hz), 7.18 (1H, dt,
J ) 1.5, 7.4 Hz), 7.33 (1H, dt, J ) 1.5, 7.3 Hz), 7.57 (1H, dd,
J ) 1.5, 8.1 Hz); 13C NMR (CDCl3) δ: 31.9, 35.7, 54.0, 118.5,
126.6, 127.2, 128.4, 128.7, 129.4, 131.9, 132.2, 139.0, 146.5,
165.3; MS (m/z) 243 (M+), 228. Anal. Calcd for C16H21NO:
C, 78.97; H, 8.70; N, 5.76. Found: C, 79.06; H, 8.55; N, 5.61.
(R)-N-(2-ter t-Bu tylph en yl)-2-m eth ylsu ccin im ide (5a an d
5b). To a solution of (R)-methylsuccinic acid (1.59 g, 12 mmol)
and o-tert-butylaniline (1.56 mL, 10 mmol) in CH2Cl2 (4 mL)
was added 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide
hydrochloride (EDC) (2.3 g, 12 mmol) under argon atmosphere
at room temperature. After being stirred for 15 h, the mixture
was poured into 2% HCl and extracted with Et2O. The Et2O
extracts were washed with brine, dried over MgSO4, and
evaporated to dryness. Purification of the residue by column
chromatography (hexane/AcOEt ) 7) gave 5b (less polar, 810
mg, 33%) and 5a (more polar, 1.03 g, 42%). The optical purity
of 5a (89% ee, 1.03 g) was improved to 96% ee (0.453 g, 44%
yield) by recrystallization from hexane-AcOEt (30 mL-3 mL).
solution and extracted with AcOEt. The AcOEt extracts were
washed with 2% HCl and brine, dried over MgSO4, and
evaporated to dryness. The residue was purified by column
chromatography (hexane/AcOEt ) 20) to give a mixture of
major-endo-6, minor-endo-6, and exo-6 (285 mg, 92%, major-
endo-6/minor-endo-6/exo-6 ) 29/1/1). Further purification by
MPLC (hexane/AcOEt ) 12) gave major-endo-6 (263 mg, 85%),
minor-endo-6 (3 mg, 1%), and exo-6 (2 mg, 0.7%).
(3R,4R,6R), (3R,4S,6R), a n d (3S,4S,6S)-N-Allyl-N-(2-
ter t-b u t ylp h en yl)b icyclo[2.2.1]h ep t en e-4-ca r b oxa m id e
[en d o-6 (m a jor ), exo-6, en d o-6 (m in or )]. Major-endo-6:
colorless solid; mp 65-66 °C; [R]22D ) +243.9 (96% ee, c ) 1.0,
CHCl3); IR (KBr) 2980, 1646 cm-1 1H NMR (CDCl3) δ 0.94
;
(1H, d, J ) 8.1 Hz), 1.21 (1H, ddd, J ) 1.9, 4.3, 8.1 Hz), 1.36
(9H, s), 1.48 (1H, ddd, J ) 2.5, 4.7, 11.3 Hz), 1.56-1.65 (1H,
m), 2.61 (1H, ddd, J ) 3.5, 4.7, 8.2 Hz), 2.77 (1H, brs), 2.83
(1H, brs), 3.26 (1H, dd, J ) 8.2, 14.2 Hz), 4.90 (1H, tdd, J )
1.4, 4.8, 14.2 Hz), 5.06 (1H, qd, J ) 1.1, 17.1 Hz), 5.14 (1H, d,
J ) 9.6 Hz), 5.89 (1H, dd, J ) 3.0, 5.5 Hz), 5.97 (1H, dddd, J
) 4.8, 8.2, 9.6, 17.1 Hz), 6.28 (1H, dd, J ) 3.0, 5.5 Hz), 7.12
(1H, dd, J ) 1.6, 7.7 Hz), 7.23 (1H, dt, J ) 1.6, 7.2 Hz), 7.34
(1H, dt, J ) 1.6, 7.2 Hz), 7.57 (1H, dd, J ) 1.6, 8.1 Hz); 13C
NMR (CDCl3) δ: 30.2, 32.2, 36.0, 42.0, 43.0, 46.8, 50.3, 54.2,
117.9, 126.4, 128.4, 129.6, 130.7, 132.1, 133.2, 137.2, 140.0,
5a : colorless solid; mp 103-106 °C; [R]26 ) +9.9 (96% ee, c
D
1
) 1.0, CHCl3); IR (KBr) 2968, 1710 cm-1; H NMR (CDCl3) δ
1.31 (9H, s), 1.47 (3H, d, J ) 7.2 Hz), 2.50 (1H, dd, J ) 4.2,
17.3 Hz), 3.02 (1H, m), 3.09 (1H, dd, J ) 9.2, 17.3 Hz), 6.84
(1H, dd, J ) 1.5, 7.8 Hz), 7.29 (1H, dt, J ) 1.4, 7.6 Hz), 7.39
(1H, dt, J ) 1.5, 7.9 Hz), 7.58 (1H, dd, J ) 1.4, 8.0 Hz); 13C
NMR (CDCl3) δ: 16.6, 31.6, 35.2, 35.6, 37.0, 127.3, 128.7, 129.6,
130.5, 130.6, 147.9, 176.7, 180.3; MS (m/z) 245 (M+), 230. Anal.
Calcd for C15H19NO2: C, 73.44; H, 7.81; N, 5.71. Found: C,
146.2, 174.1; MS (m/z) 309 (M+), 294. Anal. Calcd for C21H27
-
NO: C, 81.51; H, 8.79; N, 4.53. Found: C, 81.41; H, 8.75; N,
4.41. Minor-endo-6: colorless oil; 1H NMR (CDCl3) δ 0.95 (1H,
d, J ) 8.2 Hz), 1.04 (1H, ddd, J ) 2.4, 5.7, 11.2 Hz), 1.27 (1H,
m), 1.41 (9H, s), 1.56 (1H, m), 2.59 (1H, ddd, J ) 3.0, 5.6, 9.2
Hz), 2.71 (1H, brs), 2.92 (1H, brs), 3.27 (1H, dd, J ) 8.2, 14.2
Hz), 4.91 (1H, tdd, J ) 1.3, 5.0, 14.2 Hz), 5.01 (1H, dd, J )
1.1, 17.2 Hz), 5.09 (1H, d, J ) 10.1 Hz), 5.92 (1H, dddd, J )
5.0, 8.2, 10.1, 17.2 Hz), 6.14 (1H, dd, J ) 3.0, 5.5 Hz), 6.36
(1H, dd, J ) 3.0, 5.5 Hz), 6.86 (1H, dd, J ) 1.6, 7.6 Hz), 7.17
(1H, dt, J ) 1.6, 7.6 Hz), 7.32 (1H, dt, J ) 1.6, 7.2 Hz), 7.58
(1H, dd, J ) 1.6, 7.2 Hz); MS (m/z) 309 (M+), 294. exo-6:
73.64; H, 7.76; N, 5.56. 5b: colorless oil; [R]26 ) +5.3 (90%
D
ee, c ) 1.05, CHCl3); IR (KBr) 2986, 1713 cm-1
;
1H NMR
(CDCl3) δ 1.30 (9H, s), 1.46 (3H, d, J ) 7.1 Hz), 2.51 (1H, dd,
J ) 4.3, 17.7 Hz), 3.02 (1H, m), 3.11 (1H, dd, J ) 9.3, 17.7
Hz), 6.83 (1H, dd, J ) 1.5, 7.8 Hz), 7.28 (1H, dt, J ) 1.5, 7.6
Hz), 7.38 (1H, dt, J ) 1.5, 7.6 Hz), 7.58 (1H, dd, J ) 1.4, 8.1
Hz); 13C NMR (CDCl3) δ: 16.5, 31.5, 35.1, 35.5, 36.9, 127.3,
128.7, 129.7, 130.3, 130.6, 147.9, 176.5, 180.6; MS (m/z) 245
(M+), 230. Anal. Calcd for C15H19NO2: C, 73.44; H, 7.81; N,
5.71. Found: C, 73.50; H, 7.79; N, 5.47.
1
colorless oil; H NMR (CDCl3) δ 1.01 (1H, ddd, J ) 2.3, 8.3,
11.0 Hz), 1.24 (1H, d, J ) 8.0 Hz), 1.33 (9H, s), 1.89 (1H, ddd,
J ) 1.0, 4.4, 8.1 Hz), 1.98-2.06 (2H, m), 2.74 (1H, brs), 2.89
(1H, brs), 3.34 (1H, dd, J ) 8.2, 14.2 Hz), 4.96 (1H, tdd, J )
1.4, 4.8, 14.2 Hz), 5.08 (1H, qd, J ) 1.6, 17.1 Hz), 5.16 (1H, d,
J ) 10.2 Hz), 5.70 (1H, dd, J ) 3.0, 5.6 Hz), 5.96 (1H, dd, J )
3.0, 5.6 Hz), 6.03 (1H, dddd, J ) 4.8, 8.2, 10.2, 17.1 Hz), 7.07
(1H, dd, J ) 1.7, 7.6 Hz), 7.21 (1H, dt, J ) 1.6, 7.6 Hz), 7.30
(1H, dt, J ) 1.6, 7.2 Hz), 7.53 (1H, dd, J ) 1.6, 7.2 Hz); MS
(m/z) 309 (M+), 294.
N-(2-ter t-Bu t ylp h en yl)-2-m et h ylm a lein im id e [(+)-2].
To a solution of 5a (313 mg, 1.28 mmol) in toluene (13 mL)
was added TMS2NNa (1 M THF solution, 1.28 mL, 1.28 mmol)
at -78 °C. After being stirred for 10 min at -78 °C, PhSeCl
(245 mg, 1.28 mmol) was added to the reaction mixture, and
then the mixture was stirred for 1.5 h at -78 °C. The mixture
was poured into 2% HCl and extracted with AcOEt. The
AcOEt extracts were washed with brine, dried over MgSO4,
and evaporated to dryness. To the residue were added THF
(5 mL) and 30% H2O2 (2 mL) at 0 °C, and then the mixture
was stirred for 1.5 h at room temperature. The mixture was
poured into aqueous Na2S2O3 solution and extracted with
AcOEt. The AcOEt extracts were washed with brine, dried
over MgSO4, and evaporated to dryness. Purification of the
residue by column chromatography (hexane/AcOEt ) 12) gave
(+)-2 (133 mg, 43%). The ee of (+)-2 (96% ee) was determined
by HPLC analysis using a CHIRALPAK AD column [25 cm ×
0.46 cm i.d.; 1% i-PrOH in hexane; flow rate, 1.0 mL/min; (-)-
2; tR ) 10.5 min, (+)-2; tR ) 11.9 min]. (+)-2: colorless oil;
(4R)-Bicyclo[2.2.1]h ep ten e-4-m eth a n ol (9). To a solu-
tion of endo-6 (257 mg, 0.83 mmol) in THF (5 mL) was added
LiAlH4 (31.5 mg, 0.83 mmol) at 0 °C. After being stirred for
5 h at room temperature, the mixture was successively treated
with AcOEt, H2O, and 2% HCl and then extracted with Et2O.
The Et2O extracts were washed with brine, dried over MgSO4,
and evaporated to dryness. Purification of the residue by
column chromatography (pentane/Et2O ) 5) gave 9 (53 mg,
51%). 9: [R]24D ) +79.3 (c ) 0.86, 95% EtOH) [lit. [R]D ) +61.9
1
(68% ee, c ) 0.6, 95% EtOH)]; H NMR data coincided with
that reported in the literature.13
Ca tion ic Iod ocycliza tion In ter m ed ia te (1A). To a solu-
tion of the anilide 1 (52 mg, 0.21 mmol) in CDCl3 (8 mL) was
added I2 (161 mg, 0.63 mmol) at room temperature. After
being stirred for 2 h, the 1H NMR spectrum of the reaction
[R]D ) +1.3 (96% ee, c) 1.1, CHCl3); IR (KBr) 2960, 1703 cm-1
;
1H NMR (CDCl3) δ 1.29 (9H, s), 2.18 (3H, d, J ) 1.9 Hz), 6.51
(1H, q, J ) 1.9 Hz), 6.89 (1H, dd, J ) 1.4, 7.7 Hz), 7.26 (1H,
dt, J ) 1.4, 7.7 Hz), 7.38 (1H, dt, J ) 1.6, 8.1 Hz), 7.57 (1H,
dd, J ) 1.6, 8.1 Hz); 13C NMR (CDCl3) δ: 11.1, 31.5, 35.3, 127.1,
128.2, 128.4, 129.6, 129.7, 131.3, 146.6, 149.4, 170.8, 171.8;
MS (m/z) 243 (M+), 228. Anal. Calcd for C15H17NO2: C, 74.05;
H, 7.04; N, 5.76. Found: C, 74.21; H, 6.89; N, 5.87.
1
mixture was measured. In H NMR of 1A, two sets of signals
which may be due to the diastereomer on the basis of axial
chirality and newly constructed asymmetric center were
observed in a ratio of 2.9:1. Major-1A: 1H NMR (CDCl3) δ
1.48 (9H, s), 4.02 (1H, dd, J ) 3.0, 11.9 Hz), 4.11 (1H, dd, J )
4.9, 11.9 Hz), 4.48 (1H, dd, J ) 9.1, 12.8 Hz), 5.14 (1H, dd, J
) 9.8, 12.8 Hz), 5.84 (1H, m), 6.13 (1H, dd, J ) 11.0, 17.2 Hz),
6.73 (1H, d, J ) 11.0 Hz), 7.19 (1H, d, J ) 17.2 Hz), 7.50-
7.87 (4H, m). Minor-1A: 1H NMR (CDCl3) δ 1.48 (9H, s), 3.81
(1H, dd, J ) 6.4, 11.7 Hz), 3.86 (1H, dd, J ) 4.6, 11.7 Hz),
4.58 (1H, dd, J ) 8.2, 12.6 Hz), 5.03 (1H, dd, J ) 10.5, 12.6
Hz), 5.84 (1H, m), 6.04-6.17 (2H, m), 6.73 (1H, d, J ) 11.0
Hz), 7.19 (1H, d, J ) 17.2 Hz), 7.50-7.87 (4H, m).
Gen er a l P r oced u r e of Iod in e-Med ia ted Diels-Ald er
Rea ction . To a solution of (+)-1 (96% ee, 243 mg, 1 mmol) in
AcOEt (5 mL) was added I2 (508 mg, 2 mmol) at room
temperature. After being stirred for 30 min, cyclopentadiene
(0.16 mL, 2 mmol) was added, and then the reaction mixture
was stirred for 15 h at -78 °C to room temperature. n-Bu4NI
(739 mg, 2 mmol) was added to the mixture, and after being
stirred for 2 h, the mixture was poured into aqueous Na2S2O3