1572 J . Org. Chem., Vol. 67, No. 5, 2002
Bertilsson et al.
25
[R]D +55.4 (c 0.48, CH2Cl2); IR (neat) 2976, 1688, and 1649
m), 1.66-1.40 (2H, m), 1.44 and 1.43 (9H, each s), 1.23 (3H,
d, J ) 6.5 Hz), 1.18 (3H, d, J ) 6.5 Hz), and 1.16 (1H, t, J )
6.0 Hz); 13C NMR (mixture of rotamers) δ 172.1, 172.0, 154.3,
153.4, 79.3, 79.1, 57.1, 57.0, 54.0, 53.8, 53.1, 52.7, 47.1, 47.0,
31.9, 30.9, 30.4, 28.9, 28.8, 28.3, 28.2, 24.5, 23.4, 23.0, 22.7,
18.9, and 18.2; MS (EI) m/z (rel intensity) 296 (M+, 7),
223 (15), 114 (100), 98 (54), and 70 (87). Anal. Calcd for
cm-1; H NMR (mixture of rotamers) δ 4.41-4.38 and 4.26-
1
4.22 (1H, each m), 4.22 (1H, sept, J ) 6.3 Hz), 4.00 and 3.95
(1H each t, J ) 6.5 Hz), 3.92 and 3.83 (1H, each s), 2.43-2.38
(1H, m), 2.21-2.02 (3H, m), 1.79-1.67 (2H, m), 1.66-1.54 (2H,
m), 1.54-1.36 (2H, m), 1.44 and 1.37 (9H, each s), 1.34 and
1.24 (3H, each d, J ) 6.5 Hz), 1.17-1.12 (1H, m), 1.11 and
1.09 (3H, each d, J ) 6.3 Hz); 13C NMR (mixture of rotamers)
δ 168.2, 168.1, 154.1, 153.1, 79.3, 78.9, 63.65, 63.60, 57.2, 56.0,
52.8, 52.54, 52.47, 52.4, 42.9, 42.2, 34.3, 33.6, 30.8, 30.7, 30.6,
30.4, 28.43, 28.38, 28.3, 28.22, 28.20, 28.1, 21.84, 21.81 18.8,
and 18.7; GC-MS (EI) m/z (rel intensity) 323 (M+ + 1, 11), 249
(18), 196 (30), 140 (100), and 98 (30). Anal. Calcd for
C
16H28N2O3: C, 64.83; H, 9.52; N, 9.45. Found: C, 64.64; H,
9.50; N, 9.50.
(2S)-2-[N-(tr a n s-(2S,5S)-2,5-Dim et h yl)p yr r olid in yl]-
m eth ylp yr r olid in e (7). The procedure described for 4 was
followed using 13 (0.53 g, 1.78 mmol), which gave 7 (0.32 g,
1.76 mmol) in quantitative yield: [R]25 + 66.8 (c 1.25, CH2-
D
Cl2); IR (neat) 3406, and 1632 cm-1; 1H NMR δ 3.17-3.35 (1H,
m), 3.10-3.00 (2H, m), 2.94 (1H, dt, J ) 13.4, 9.9 Hz), 2.83
(1H, dt, J ) 13.4, 9.4 Hz), 2.42 (1H, dd, J ) 12.2, 4.0 Hz), 2.33
(1H, dd, J ) 12.2, 10.3 Hz), 2.03-1.80 (3H, m), 1.73 (2H, pent,
J ) 7.2 Hz), 1.43-1.22 (3H, m), and 0.93 (6H, d, J ) 6.3 Hz);
13C NMR δ 55.8, 54.6, 51.8, 45.3, 30.8, 29.6, 24.7, and 17.0;
GC-MS (EI) m/z (rel intensity) 183 (M+ + 1, 1), 112 (100), 98
(90), and 70 (32). Anal. Calcd for C11H22N2‚H2O: C, 65.95; H,
12.08; N, 13.98. Found: C, 65.76; H, 11.88; N, 13.34.
Ca ta lytic Rea r r a n gem en t of Ep oxid es: Gen er a l P r o-
ced u r e. n-BuLi (0.30 mL, 0.48 mmol, 1.6 M in hexane) was
added dropwise over 5 min to a solution of diamine 1 or 3-7
(15 µmol), diisopropylamine (0.64 mL, 0.46 mmol), and DBU
(5 equiv for the substrate screening, otherwise as indicated in
the tables) in THF (1.5 mL) at 0 °C. The resulting solution
was stirred at 0 °C for 30 min, and the epoxide (0.3 mmol) in
THF (1.0 mL) containing n-dodecane (ca. 10 mg, as the internal
standard for GC analysis) was then added dropwise over a
period of 5 min. The reaction mixture was stirred at the
temperature indicated until the reaction ceased (according to
GC analysis, which was also used for determining the ee of
the formed allylic alcohol). The reaction mixture was then
diluted with Et2O (15 mL) and washed with 10% aqueous citric
acid (2 × 5 mL), water (5 mL), and brine (5 mL) and dried
(MgSO4). The crude alcohol was purified by column chroma-
tography.
Stoich iom etr ic Rea r r a n gem en t of Ep oxid es: Gen er a l
P r oced u r e. This procedure was performed as described for
the catalytic reaction but with the following modifications in
amounts of reagents: diamine, 0.60 mmol; n-BuLi, 0.41 mL
(0.65 mmol, 1.6 M in hexane); and epoxide, 0.5 mmol.
(1R)-Cyclop en t-2-en -1-ol (14). Cyclopentene oxide (26 mg,
0.31 mmol) was transformed at room temperature to the
corresponding allylic alcohol (R)-14. The reaction was judged
to have ceased after 14 h (90% conversion, 96% ee). After
workup, the crude allylic alcohol was benzoylated9a and
purified by column chromatography (silica, pentane/EtOAc 90:
10) to give the benzoate ester of 14 (47 mg, 81%). (R)-14:
colorless oil; GC (68 °C isotherm): tR (S) ) 18.17 min, tR (R) )
18.64 min.
(1R)-Cycloh ex-2-en -1-ol (15). Cyclohexene oxide (30 mg,
0.31 mmol) was rearranged at 0 °C to the allylic alcohol (R)-
15, using diamines 1 and 4-7. The conversion was determined
after 2 h (on the basis of epoxide consumption relative to the
internal standard, n-dodecane). When the reactions were
complete, workup and column chromatography (silica, pen-
tane/Et2O from 90:10 to 60:40) gave 15 in the yield and with
the ee indicated in the Table 1. The spectroscopic properties
of the isolated allylic alcohol were identical to those reported.19
(R)-15: GC (100 °C isotherm): tR (S) ) 11.50 min, tR (R) )
11.98 min.
(1R,4S,5S)-4,5-Dim et h yl-cycloh ex-2-en -1-ol (16) a n d
(1R,4S,5R)-4,5-Dim eth yl-cycloh ex-2-en -1-ol (17). A 90:10
mixture of (1R*,2S*,4R*,5S*)-(1,4-syn,4,5-syn)-4,5-dimethyl-
1-oxabicyclo[4.1.0]heptane and (1R*,2S*,4S*,5R*)-(1,4-anti,4,5-
syn)-4,5-dimethyl-1-oxabicyclo[4.1.0]heptane (39 mg, 0.31 mmol)
was transformed into the allylic alcohols 16 and 17. The
reaction was judged to have ceased after 6 h at 0 °C (at >95%
C
18H30N2O3: C, 67.05; H, 9.38; N, 8.69. Found: C, 66.87; H,
9.48; N, 8.59.
(1S,3R,4R)-3-[N-(tr a n s-(2S,5S)-2,5-Dim eth yl)p yr r olid i-
n yl]m eth yl-2-a za bicyclo[2.2.1]h ep ta n e (5). The procedure
described for 4 was followed using 11 (0.37 g, 1.15 mmol),
25
which gave 5 (0.22 g, 91%): [R]D + 49.9 (c 3.30, CHCl3); IR
(neat) 3436, and 1639 cm-1 1H NMR δ 3.36-3.38 (1H, m),
.
3.01-2.93 (2H, m), 2.75 (1H, dd, J ) 9.5, 4.8 Hz), 2.33-2.37
(1H, m), 2.28 (1H, dd, J ) 12.5, 9.5 Hz), 2.21 (1H, dd, J )
12.5, 4.8 Hz), 1.98-1.85 (2H, m), 1.70 (1H, br s), 1.64-1.51
(2H, m), 1.47 (1H, dpent, J ) 9.8, 2.0 Hz), 1.36-1.23 (4H, m),
1.10 (1H, dt, J ) 9.8, 1.3 Hz), and 0.90 (6H, d, J ) 6.3 Hz);
13C NMR δ 59.9, 55.7, 55.0, 53.4, 39.1, 34.2, 32.7, 30.7, 28.9,
and 17.0; GC-MS (EI) m/z (rel intensity) 208 (M+, <1), 112
(100), 98 (92), and 96 (12). Anal. Calcd for C13H24N2‚0.2H2O:
C, 73.67; H, 11.60; N, 13.22. Found: C, 73.81; H, 11.65; N,
13.07.
(1S,3R,4R)-N-ter t-Bu toxyca r bon yl-3-[N-(tr a n s-(2R,5R)-
2,5-d iet h yl)p yr r olid in yl]ca r b on yl-2-a za b icyclo[2.2.1]-
h ep ta n e (12). The procedure for 10 was followed using 9 (1.00
g, 4.14 mmol) and trans-(2R,5R)-diethylpyrrolidine‚HCl (1.02
g, 6.22 mmol) to obtain 12 (1.10 g, 76%): mp 134-135 °C; [R]25
D
-8.74 (c 1.0, CH2Cl2); IR (neat) 2969, 1695, and 1645 cm-1
;
1H NMR (mixture of rotamers) δ 4.32-4.30 and 4.21-4.19 (1H,
each m), 4.15-4.08 and 3.94-3.82 (2H, each m), 3.79 and 3.67
(1H, each s), 2.73 and 2.66 (1H, each dt, J ) 9.5, 2.0 Hz), 2.52-
2.47 (1H, m), 2.19-1.59 (8H, m), 1.53-1.23 (3H, m), 1.43 and
1.40 (9H, each s), 1.19-1.23 (1H, m), 1.13-1.01 (1H, m), 0.94
and 0.83 (6H, each t, J ) 7.3 Hz); 13C NMR (mixture of
rotamers) δ 170.0, 169.9, 153.9, 153.1, 79.4, 79.1, 62.6, 60.5,
60.3, 59.3, 58.9, 56.9, 55.9, 43.9, 43.0, 35.2, 34.4, 30.8, 30.3,
29.3, 28.9, 28.51, 28.45, 28.40, 28.3, 27.6, 27.4, 25.9, 25.7, 25.0,
24.5, 11.5, 10.9, 10.8, and 10.7; GC-MS (EI) m/z (rel intensity)
351 (M+ + 1, 10), 140 (100), and 126 (24). Anal. Calcd for
C
20H34N2O3: C, 68.54; H, 9.78; N, 7.99. Found: C, 68.28; H,
9.87; N, 8.00.
(1S,3R,4R)-3-[N-(tr a n s-(2R,5R)-2,5-Dieth yl)pyr r olidin yl]-
m eth yl-2-a za bicyclo[2.2.1]h ep ta n e (6). The procedure de-
scribed for 4 was followed using 12 (0.82 g, 2.34 mmol), which
gave 6 (0.52 g, 95%): [R]25 -63.9 (c 1.5, CH2Cl2); IR (neat)
D
3430, and 1637 cm-1
;
1H NMR δ 3.39-3.37 (1H, m), 2.83-
2.75 (2H, m), 2.76 (1H, dd, J ) 9.6, 5.7 Hz), 2.57 (1H, dd, J )
12.4, 5.7 Hz), 2.17 (1H, dd, J ) 12.4, 9.6 Hz), 2.12-2.09 (1H,
m), 2.04 (1H, br s), 1.60-1.48 (4H, m), 1.46-1.29 (7H, m),
1.21-1.17 (1H, m), 1.12-0.98 (2H, m), and 0.81 (6H, t, J )
7.3 Hz); 13C NMR δ 62.4, 61.9, 60.5, 55.7, 52.0, 40.2, 35.6, 34.9,
31.5, 28.7, 27.5, 23.1, 18.9, 13.9, and 10.6; GC-MS (EI) m/z
(rel intensity) 236 (M+, <1), 209 (11), 140 (91), and 112 (100).
Anal. Calcd for C15H28N2‚0.1H2O: C, 75.64; H, 11.93; N, 11.76.
Found: C, 75.73; H, 11.70; N, 11.59.
(2S)-N-ter t-Bu toxycar bon yl-2-[N-(tr a n s-(2S,5S)-2,5-dim -
eth yl)p yr r olid in yl]-ca r bon ylp yr r olid in e (13). Boc-amide
13 (0.53 g, 1.78 mmol) was prepared in 77% yield from N-Boc-
proline18 (0.50 g, 2.32 mmol) following the procedure described
for 10. 13: mp 128-130 °C; Rf 0.24 (silica, pentane/EtOAc 1:2);
[R]22 + 25.6 (c 0.9, CH2Cl2); 1H NMR (mixture of rotamers) δ
D
4.46 and 4.36 (1H, each m), 4.21 (2H, pent, J ) 6.5 Hz), 3.67
and 3.60 (1H, each ddd, J ) 9.5, 8.1, 4.3 Hz), 3.46 and 3.39
(1H, each dt, J ) 10.1, 7.2 Hz), 2.44-1.95 (4H, m), 1.84 (1H,
(19) Brown, H. C.; Bhat, K. S.; J adhav, P. K.; J . Chem. Soc., Perkin
Trans. 1 1991, 2633-2638.
(18) Einhorn, J .; Einhorn, C.; Luche, J .-L. Synlett 1991, 37-38.