Pearson et al.
2.03 (m, 1 H), 1.83-1.50 (m, 7 H); 13C NMR (100 MHz, CDCl3)
δ 177.44, 177.09, 131.75, 129.07, 128.53, 126.43, 68.84, 57.26,
53.52, 52.83, 43.82, 33.22, 27.05, 26.22, 25.33; MS (EI, 70 eV)
m/z (rel intensity) 284 (M+, 100), 269 ([M - CH3]+, 10), 255
([M - C2H5]+, 58), 242 ([M - C3H7]+, 94), 111 ([M - N-
phenylmaleimide]+, 78); HRMS (EI, 70 eV) calcd for C17H20N2O2
(M+) 284.1525, found 284.1518.
were heated in toluene (1.5 mL) at reflux for 1.5 h. The reaction
was concentrated and the residue chromatographed (20% ethyl
acetate/hexanes) to afford 32 mg (63%) of the title compounds
as an inseparable mixture of two diastereomers (3:2), both as
clear oils. Data for the mixture: Rf ) 0.51 (30% ethyl acetate/
1
hexanes); H NMR (300 MHz, CDCl3) δ 7.45-7.20 (m, 5 H),
5.05 (dd, J ) 9.2, 6.2 Hz, 1 H × 0.60, H-2), 4.94 (dd, J ) 8.8,
2.4 Hz, 1 H × 0.40, H-2), 3.70 (s, 1 H × 0.60, H-8a), 3.50 (dd,
J ) 9.7, 3.5 Hz, 1 H × 0.60), 3.36 (s, 1 H × 0.40, H-8a), 3.08
(dd, J ) 8.7, 6.3 Hz, 1 H × 0.40), 3.02-2.88 (m, 1 H), 2.78 (t,
J ) 8.8 Hz, 1 H × 0.40), 2.48 (t, J ) 9.5 Hz, 1 H × 0.60), 2.32
(td, J ) 9.9, 3.3 Hz, 1 H × 0.60), 2.08 (td, J ) 11.1, 3.1 Hz, 1
H × 0.40), 1.84-1.62 (m, 2 H × 0.60), 1.62-1.42 (m, 2 H),
1.30-1.18 (m, 2 H × 0.40), 1.17 (s, 3 H × 0.40), 1.07 (s, 3 H ×
0.60), 1.06 (s, 3 H × 0.60), 1.03 (s, 3 H × 0.40); 13C NMR (90
MHz, CDCl3) δ 128.4, 128.2, 127.3, 126.5, 125.7, 101.4, 101.3,
76.6, 76.3, 62.2, 60.3, 50.8, 50.0, 37.1, 35.7, 34.0, 33.4, 27.3,
27.1, 21.9, 21.7, 20.9, 19.7; MS (EI, 70 eV) m/z (rel intensity)
231 (M+, 16), 230 ([M - H]+, 14), 216 ([M - CH3]+, 3), 125 ([M
- PhCHO]+, 100), 104 (PhCHO+, 69), 91 (PhCH2+, 11); HRMS
(EI, 70 eV) calcd for C15H21NO (M+) 231.1623, found 231.1615.
Octa h yd r o-8,8-d im eth yl-1-in d olizid in eca r boxylic Acid
Meth yl Ester a n d Octa h yd r o-8,8-d im eth yl-2-in d olizid i-
n eca r boxylic Acid Meth yl Ester (26). Imine 1 (130 mg, 0.29
mmol) and methyl acrylate (47 mg, 0.54 mmol) were heated
at reflux in toluene (0.5 mL) for 3 h. The reaction was
concentrated and the residue chromatographed (40% ethyl
acetate/hexanes) to give 48 mg (79%) of the title compound as
a clear oil containing three inseparable isomers (1:1:1.8 by GC).
Both the regio- and stereochemistry could not be determined.
Data for the mixture: Rf ) 0.23 (40% ethyl acetate/hexanes);
IR (CHCl3) 1738 (s) cm-1; 1H NMR (400 MHz, CDCl3) δ 3.692
(s, 3 H), 3.688 (s, 3 H), 3.678 (s, 3 H), 3.38-3.26 (m, 2 H), 3.10-
2.90 (m, 4 H), 2.90-2.64 (m, 2 H), 2.30-2.16 (m, 3 H), 2.10-
1.56 (m, 15 H), 1.56-1.35 (m, 6 H), 1.20-1.10 (m, 3 H), 0.97
(s, 3 H), 0.94 (s, 3 H), 0.92 (s, 3 H), 0.87 (s, 3 H), 0.86 (s, 3 H),
0.81 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ 177.0, 175.75,
175.72, 76.0, 72.9, 72.1, 58.3, 57.5, 54.4, 53.54, 53.47, 53.43,
51.8, 51.7, 51.6, 43.2, 39.6, 39.33, 39.26, 39.23, 39.1, 32.65,
32.24, 32.17, 29.0, 28.9, 28.8, 28.7, 28.3, 27.7, 22.2, 22.1, 22.0,
19.3, 19.1, 18.9; MS (EI, 70 eV) m/z (rel intensity) 211 (M+,
30), 210 ([M - H]+, 17), 196 ([M - CH3]+, 40), 180 ([M -
OCH3]+, 26), 152 ([M - CO2CH3]+, 34), 142 (100), 125 ([M -
CH2CHCO2CH3]+, 19); HRMS (EI, 70 eV) calcd for C12H21NO2
(M+) 211.1572, found 211.1565.
The regiochemistry was determined based on the splitting
pattern of the bridgehead hydrogen H-8a. The stereochemistry
of the major isomer could not be determined.
Hexa h yd r o-8,8-d im eth yl-2,2-d ip h en yl-5H-oxa zolo[3,2-
a ]p yr id in e (29). Imine 1 (100 mg, 0.43 mmol) and benzophe-
none (75 mg, 0.43 mmol) were heated to reflux in toluene (2
mL) for 1.5 h. The reaction was concentrated and the residue
chromatographed (10% ethyl acetate/hexanes) to afford 87 mg
(66%) of the title compound as a colorless oil: Rf ) 0.20 (10%
ethyl acetate/hexanes); 1H NMR (300 MHz, CDCl3) δ 7.50-
7.10 (m, 10 H), 3.89 (d, J ) 9.1 Hz, 1 H), 3.53 (s, 1 H), 3.02 (d,
J ) 9.1 Hz, 1 H), 2.95-2.87 (m, 1 H), 2.12 (td, J ) 10.6, 3.1
Hz, 1 H), 1.75-1.60 (m, 1 H), 1.54-1.40 (m, 1 H), 1.23-1.14
(m, 1 H), 1.10 (s, 3 H), 1.08 (s, 3 H); 13C NMR (90 MHz, CDCl3)
δ 128.2, 127.9, 126.7, 126.6, 126.3, 125.9, 100.7, 83.7, 67.2, 50.4,
36.5, 33.6, 27.1, 21.7, 20.4; MS (EI, 70 eV) m/z (rel intensity)
307 (M+, 9), 180 (Ph2CO+, 51), 125 ([M - Ph2CO]+, 100), 77
(Ph+, 22); HRMS (EI, 70 eV) calcd for C21H25NO (M+) 307.1936,
found 307.1924.
(1S*,2R*,8a R*)-Octa h yd r o-8,8-d im eth yl-2-p h en yl-1-in -
d olizin eca r boxylic Acid Meth yl Ester (30a ), (1S*,2R*,
8a R*)-Octa h yd r o-8,8-d im eth yl-1-p h en yl-2-in d olizin eca r -
boxylic Acid Meth yl Ester (30b), a n d (1R*,2S*,8a R*)-
Octa h yd r o-8,8-d im eth yl-1-p h en yl-2-in d olizin eca r boxyl-
ic Acid Meth yl Ester (30c). Imine 1 (300 mg, 0.66 mmol)
and trans-methyl cinnamate (161 mg, 1.0 mmol) were heated
to reflux in toluene (4 mL) for 6 h. The reaction was
concentrated and the residue chromatographed (15% to 25%
ethyl acetate/hexanes, gradient) to afford 81 mg (42%) of 30a ,
8 mg (4%) of 30b, and 40 mg (22%) of 30c, all as light yellow
oils.
(1S*,2R*,8a R*)- (27a ) a n d (1R*,2S*,8a R*)-Octa h yd r o-
8,8-d im eth yl-1,2-in d olizin ed ica r boxylic Acid Dim eth yl
Ester (27b). Imine 11 (490 mg, 1.09 mmol) and dimethyl
maleate (160 mg, 1.11 mmol) were heated to reflux in toluene
(2 mL) for 5 h. The reaction was concentrated and the residue
chromatographed (20% to 40% ethyl acetate/hexanes, gradient)
to provide 119 mg (41%) of 27a and 92 mg (31%) of 27b, both
as yellow oils.
27a (exo): Rf ) 0.23 (20% ethyl acetate/hexanes); IR (CHCl3)
1736 (s) cm-1; 1H NMR (300 MHz, CDCl3) δ 3.66 (s, 3 H), 3.64
(s, 3 H), 3.21-3.01 (m, 4 H, H-1, H-2, H-3, and H-5), 2.70-
2.62 (m, 1 H), 2.17 (d, J ) 8.4 Hz, 1 H, H-8a), 2.04 (dt, J )
10.0, 3.0 Hz, 1 H), 1.72-1.61 (m, 1 H), 1.50-1.40 (m, 2 H),
1.14 (dt, J ) 11.1, 4.7 Hz, 1 H), 0.95 (s, 3 H), 0.81 (s, 3 H); 13
C
NMR (75 MHz, CDCl3) δ 174.6, 172.1, 76.4, 56.4, 53.1, 51.8,
46.5, 44.8, 39.5, 32.9, 28.1, 22.0, 19.3; MS (EI, 70 eV) m/z (rel
int) 269 (M+, 49), 254 ([M - CH3]+, 47), 238 ([M - OCH3]+,
35), 210 ([M - CO2CH3]+, 42), 200 (100), 125 ([M - MeO2-
CCHdCHCO2Me]+, 31); HRMS (EI, 70 eV) calcd for C14H23
-
NO4 (M+) 269.1627, found 269.1640.
27b (endo): Rf ) 0.19 (30% ethyl acetate/hexanes); IR
(CHCl3) 1733 (s) cm-1; 1H NMR (300 MHz, CDCl3) δ 3.81 (dd,
J ) 9.8, 6.3 Hz, 1 H), 3.65 (s, 3 H), 3.64 (s, 3 H), 3.33 (dd, J )
8.0, 5.4 Hz, 1 H, H-1), 3.20-3.08 (m, 2 H, H-2 and H-5), 2.47
(dd, J ) 11.1, 9.8 Hz, 1 H), 2.15 (d, J ) 5.4 Hz, 1 H, H-8a),
1.94 (td, J ) 11.5, 3.0 Hz, 1 H), 1.79-1.69 (m, 1 H), 1.44-1.32
(m, 1 H), 1.09-0.99 (m, 1 H), 1.02 (s, 3 H), 0.86 (s, 3 H); 13C
NMR (90 MHz, CDCl3) δ 173.1, 172.2, 76.5, 55.0, 51.9, 47.5,
44.0, 41.7, 33.0, 27.9, 21.9, 18.9; MS (EI, 70 eV) m/z (rel
intensity) 269 (M+, 34), 268 ([M - H]+, 55), 254 ([M - CH3]+,
38), 238 ([M - OCH3]+, 35), 210 ([M - CO2CH3]+, 48), 200
(100), 125 ([M - MeO2CCHdCHCO2Me]+, 35); HRMS (CI,
NH3) calcd for C14H24NO4 ([M + H]+) 270.1705, found 270.1695.
30a : Rf ) 0.36 (15% ethyl acetate/hexanes); IR (CHCl3) 1729
(s) cm-1 1H NMR (300 MHz, CDCl3) δ 7.24-7.15 (m, 5 H),
;
3.90-3.78 (m, 1 H, H-2), 3.69 (s, 3 H), 3.59 (t, J ) 8.5 Hz, 1
H), 3.30-3.22 (m, 1 H), 3.08 (dd, J ) 8.6, 5.4 Hz, 1 H, H-1),
2.19 (d, J ) 8.6 Hz, 1 H, H-8a), 2.14 (t, J ) 9.6 Hz, 1 H), 1.90-
1.70 (m, 2 H), 1.50-1.35 (m, 2 H), 1.20-1.00 (m, 1 H), 1.08 (s,
3 H), 0.90 (s, 3 H); 13C NMR (100 MHz, CDCl3) δ 175.4, 143.3,
128.5, 128.3, 127.5, 126.7, 64.1, 55.0, 53.5, 51.8, 45.7, 42.7, 33.1,
29.1, 28.0, 21.6, 19.8; MS (CI, NH3) m/z (rel intensity) 288 ([M
+ H]+, 100), 287 (M+, 4); HRMS (CI, NH3) calcd for C18H26
-
NO2 ([M + H]+) 288.1963, found 288.1965. The stereochemical
assignment was based on 2D NOESY experiments, which
showed a cross-peak between H-1 and H-8a, but none between
H-1 and H-2. Assignment of proton resonances was confirmed
by COSY experiments on derivative 32a .
The stereochemical assignment of 27a and 27b was made
by 2D COSY and NOESY experiments. For 27a , there was an
NOE cross-peak between the H-1 and H-2 resonances and no
cross-peak between H-8a and H-1. For 27b, there were NOE
cross-peaks between H-8a and H-1, and H-1 and H-2.
30b: Rf ) 0.26 (15% ethyl acetae/hexanes); IR (CHCl3) 1728
(s) cm-1 1H NMR (360 MHz, CDCl3) δ 7.50-7.05 (m, 5 H),
;
(2S*,8a R*)- (28a ) a n d (2R*,8a R*)-Hexa h yd r o-8,8-d i-
m eth yl-2-p h en yl-5H-oxa zolo[3,2-a ]p yr id in e (28b). Imine
1 (100 mg, 0.22 mmol) and benzaldehyde (49 mg, 0.46 mmol)
3.67 (s, 3 H), 3.65-3.55 (m, 2 H, H-1 and H-3), 3.25-3.18 (m,
1 H), 3.10 (td, J ) 8.4, 3.0 Hz, 1 H, H-2), 2.32 (dd, J ) 9.6, 7.9
Hz, 1 H), 2.06 (d, J ) 6.6 Hz, 1 H, H-8a), 1.92-1.85 (m, 1 H),
1934 J . Org. Chem., Vol. 69, No. 6, 2004