EnantioselectiVe Synthesis of Tetraponerines
J. Am. Chem. Soc., Vol. 122, No. 40, 2000 9589
THF (10 mL) was added dropwise to the reaction mixture over 15
min. After stirring for 1 h, the solvent was removed under vacuum
and the residue was chromatographed on silica gel using MTBE/hexane
(4:1) to yield 2.9 (4.35 mmol, 87%) of 14 (yellow oil). 1H NMR (400
MHz, CDCl3): δ ) 8.00 (m, 2 H, nosyl), 7.67 (m, 4 H, nosyl), 7.59
(d, 2 H, J ) 8 Hz, nosyl), 5.87 (m, 2 H, H2, H3), 5.64 (ddt, 1 H, J )
17 Hz, 11 Hz, 7 Hz, H8), 5.19 (m, 2 H, H1, H4), 5.01 (d, 1 H, J ) 11
Hz, H9), 5.00 (d, 1 H, J ) 17 Hz, H9), 4.40 (t, 1 H, J ) 7 Hz, H13),
3.59 (m, 2 H, OCH2CH3), 3.44 (m, 2 H, OCH2CH3), 3.22 (m, 2 H,
H6), 2.90 (m, 2 H, H10), 2.27 (m, 2 H, H7), 1.96 (t, 2 H, J ) 7 Hz,
H5), 1.56-1.47 (m, 4 H, H11, H12), 1.16 (t, 6 H, J ) 7 Hz, OCH2CH3).
13C NMR (CDCl3): δ ) 148.0 (Cq, nosyl), 135.4 (CH, C2), 135.1
(CH, C3), 134.1 (CH, nosyl), 133.7 (CH, nosyl), 133.6 (CH, nosyl),
133.4 (Cq, nosyl), 133.3 (Cq, nosyl), 131.7 (CH, nosyl), 130.8 (CH,
nosyl), 124.1 (CH, C8), 117.4 (CH2, C9), 102.3 (CH, C13), 63.8 (CH,
C1), 63.7 (CH, C4), 61.3 (CH2, OCH2CH3), 44.5 (CH2, C6), 44.0 (CH2,
C10), 35.3 (CH2, C7), 33.1 (CH2, C11), 31.0 (CH2, C5), 26.3 (CH2,
C12), 15.3 (CH3, OCH2CH3). IR (film): 3074, 2975, 2929, 1734, 1543,
1439, 1372, 1352, 1163, 1121, 1059, 852, 776, 742, 652 cm-1. LRMS
m/z (%): 435 (100) [M-C3H5-nosyl+], 366 (38), 321 (98)
[M-C8H17O2N-nosyl+], 186 (84) [nosyl+], 179 (50), 103 (49), 94 (75),
85 (51). HRMS Calcd for C29H38N4O10S2 [M+]: 666.2029. Found:
666.2037. Anal. Calcd for C29H38N4O10S2: C, 52.24%; N, 8.41%; H,
(2S,8R)-N-Benzyloxycarbonyl-2-[2-N-benzyloxycarbonyl-(4,4-di-
ethoxybutyl)amino]-but-3-enyl-1,2,5,6-tetrahydropyridine (19). 1.6
g (2.84 mmol) of 18 was dissolved in dry CH2Cl2 (100 mL), and C2H4
(50 mL) was bubbled slowly through the solution. 117 mg (0.142 mmol)
of [Ru] was then added, and the mixture was stirred for 12 h at room
temperature. The solvent was removed under vacuum, and the residue
was chromatographed on silica gel using MTBE/hexane (3:7) to yield
1.55 g (2.75 mmol, 97%) of 19 (clear oil). 1H NMR (500 MHz, C6D6):
δ ) 7.30-7.00 (m, 10 H, phenyl), 6.01-5.88 (m, 1 H), 5.57 (dm, 2
H, J ) 6 Hz), 5.52 (dm, 2 H, J ) 6 Hz), 5.13 (m, 5 H), 4.97 (d, 1 H,
J ) 11 Hz), 4.72-4.61 (m, 1 H), 4.54 (m, 1 H), 4.41 (t, 1 H, J ) 7
Hz), 4.18-4.00 (m, 1 H), 3.51 (m, 2 H), 3.35 (m, 2 H), 3.33-3.16 (m,
1 H), 2.69 (ddd, 1 H, J ) 15 Hz, 6 Hz, 4 Hz), 1.99 (m, 3 H), 1.74 (m,
2 H), 1.60 (m, 2 H), 1.49 (dm, 1 H, J ) 17 Hz), 1.10 (t, 6 H, J ) 7
Hz). 13C NMR (C6D6): δ ) 155.7 (Cq), 155.0 (Cq), 137.7 (CH), 137.6
(Cq), 137.4 (Cq), 128.3-127.5 (9 C), 116.2 (CH2), 102.7 (CH), 66.9
(CH2), 66.8 (CH2), 60.8 (CH2), 60.7 (CH2), 57.5 (CH), 50.3 (CH), 45.8
(CH2), 37.2 (CH2), 37.1 (CH2), 31.4 (CH2), 25.3 (CH2), 24.7 (CH2),
15.2 (CH3). IR (film): 3065, 3033, 2974, 2943, 2896, 1695, 1455, 1415,
1287, 1138, 1069, 994, 770, 698 cm-1. LRMS m/z (%): 518 (14)
[M-C2H6O+], 427 (18) [M-Z+], 383 (22), 270 (53), 224 (18), 134
(16), 91 (100) [C7H7+]. HRMS Calcd for C33H44N2O6 [M+]: 564.3199.
Found: 564.3202. Anal. Calcd for C33H44N2O6: C, 70.19%; N, 4.96%;
20
20
5.75%. Found: C, 52.03%; N, 8.17%; H, 5.97%. [R]D ) -36.0° (c
) 1, CHCl3).
H, 7.85%. Found: C, 70.49%; N, 5.20%; H, 7.63%. [R]D ) +82.4°
(c ) 1, CHCl3).
(1S,4S)-N′-(4,4-Diethoxybutyl)-N,N′-dinosyl-N-prop-2-enylcyclo-
pent-4-ene-1,3-diamine (15). This compound was prepared from 625
mg (0.185 mmol) of 13 in 81% yield (978 mg, 0.15 mmol, yellow oil)
by a procedure similar to that employed in the synthesis of 14. (For
data, see Supporting Information.)
(2S,7R)-2-[2-(4,4-Diethoxybutyl)-N-nosylamino]but-3-enyl-N-
nosyl-2,5-dihydropyrrole (20). This compound was prepared from 1.3
g (1.98 mmol) of 11 in 89% yield (1.15 g, 1.95 mmol) by a procedure
1
similar to that employed in the synthesis of 19. H NMR (400 MHz,
CDCl3): δ ) 8.02 (m, 1 H, nosyl), 7.85 (m, 1 H, nosyl), 7.74-7.55
(m, 6 H, nosyl), 5.96 (dd, 1 H, J ) 6 Hz, 2 Hz, H3), 5.77 (d, 1 H, J
) 6 Hz, H4), 5.96 (ddd, 1 H, J ) 17 Hz, 10 Hz, 6 Hz, H8), 5.15 (d,
1 H, J ) 10 Hz, H5), 5.11 (d, 1 H, J ) 17 Hz, H5), 4.82 (m, 1 H, H7),
4.54 (m, 1 H, H2), 4.46 (t, 1 H, J ) 7 Hz, H13), 4.29 (dd, 1 H, J )
16 Hz, 1 Hz, H6), 4.12 (ddd, 1 H, J ) 6 Hz, 2 Hz, 1 Hz, H6), 3.60 (m,
2 H, OCH2CH3), 3.46 (m, 2 H, OCH2CH3), 3.29 (dd, 2 H, J ) 10 Hz,
7 Hz, H6), 2.37 (ddd, 1 H, J ) 15 Hz, 9 Hz, 4 Hz, H10), 1.98 (ddd,
1 H, J ) 15 Hz, 9 Hz, 6 Hz, H10), 1.77 (m, 2 H, H11), 1.68 (m, 2 H,
H12), 1.16 (t, 6 H, J ) 7 Hz, OCH2CH3). 13C NMR (CDCl3): δ )
148.8 (Cq, nosyl), 148.1 (Cq, nosyl), 135.8 (CH, C3), 133.7 (Cq, nosyl),
133.6 (Cq, nosyl), 133.5 (CH, nosyl), 131.8 (CH, nosyl), 131.7 (CH,
nosyl), 130.8 (CH, C4), 129.6 (CH, nosyl), 129.4 (CH, nosyl), 125.4
(CH, C8), 124.2 (CH, nosyl), 124.0 (CH, nosyl), 118.5 (CH2, C3), 102.5
(CH, C13), 65.1 (CH, C2), 61.5 (CH2, OCH2CH3), 61.3 (CH2, OCH2-
CH3), 56.6 (CH, C7), 55.2 (CH2, C5), 44.9 (CH2, C6), 39.0 (CH2, C10),
31.1 (CH2, C11), 26.2 (CH2, C12), 15.3 (CH3, OCH2CH3). IR (film):
3093, 2975, 2930, 2881, 1544, 1439, 1373, 1354, 1167, 1127, 1060,
1000, 852, 779, 742, 655 cm-1. LRMS m/z (%): 420 (36) [M-C3H9N-
nosyl+], 253 (100), 186 (92) [nosyl+], 70 (56). HRMS Calcd for
C28H35N4O10S2 [M-H+]: 651.1795. Found: 651.1797. Anal. Calcd for
C28H36N4O10S2: C, 51.25%; N, 8.58%; H, 5.56%. Found: C, 51.77%;
(2S,8S)-2-[2-(4,4-Diethoxybutyl)-N-nosylamino]but-3-enyl-N-nosyl-
1,2,5,6 -tetrahydropyridine (16). 1.4 g (2.102 mmol) of 10 was
dissolved in dry CH2Cl2 (100 mL), and C2H4 (50 mL) was slowly
bubbled through the solution. 87 mg (0.105 mmol) of [Ru] was then
added, and the mixture was stirred at 35 °C for 48 h. The solvent was
removed under vacuum, and the residue was chromatographed on silica
gel using MTBE/hexane (7:3) to yield 1.105 g (1.66 mmol, 79%) of
1
16 (yellow oil) and 225 mg (0.338 mmol, 15%) of 10. H NMR (400
MHz, CDCl3): δ ) 8.16 (d, 2 H, J ) 8 Hz, nosyl), 7.92 (d, 2 H, J )
8 Hz, nosyl), 7.74-7.56 (m, 5 H, nosyl), 7.52 (d, 2 H, J ) 8 Hz, nosyl),
5.84-5.59 (m, 3 H, H3, H4, H9), 5.22 (d, 1 H, J ) 11 Hz, H10), 5.15
(d, 1 H, J ) 17 Hz, H10), 4.45 (t, 1 H, J ) 7 Hz, H14), 4.40 (m, 1 H,
H12), 4.31 (m, 1 H, H18), 3.94 (dd, 1 H, J ) 15 Hz, 7 Hz, H7), 3.60
(m, 2 H, OCH2CH3), 3.45 (m, 2 H, OCH2CH3), 3.40-3.20 (m, 3 H,
H6, H7), 2.22-2.00 (m, 3 H, H5, H11), 1.82 (dm, 1 H, J ) 15 Hz.
H5), 1.69 (m, 2 H, H12), 1.58 (m, 2 H, H13), 1.16 (t, 6 H, J ) 7 Hz,
OCH2CH3). 13C NMR (CDCl3): δ ) 148.0 (Cq, nosyl), 147.8 (Cq,
nosyl), 134.2 (CH, nosyl), 133.7 (Cq, nosyl), 133.5 (CH, nosyl), 133.4
(CH, nosyl), 133.1 (Cq, nosyl), 132.0 (CH, nosyl), 131.6 (CH, nosyl),
130.2 (CH, nosyl), 126.9 (CH, nosyl), 125.4 (CH, C9), 124.0 (CH,
C3), 123.8 (CH, C4), 119.2 (CH2, C10), 102.4 (CH, C14), 61.4 (CH2,
OCH2CH3), 61.2 (CH2, OCH2CH3), 56.1 (CH, C2), 51.6 (CH, C8), 45.0
(CH2, C6), 38.2 (CH2, C11), 37.8 (CH2, C12), 31.0 (CH2, C7), 26.3
(CH2, C5), 23.0 (CH2, C13), 15.3 (CH3, OCH2CH3). IR (film): 3095,
3074, 2930, 2878, 1543, 1439, 1373, 1351, 1163, 1125, 1059, 999,
852, 779, 729, 678 cm-1. LRMS m/z (%): 434 (10), 267 (100) [C5H7N-
nosyl+], 186 (35) [nosyl+]. HRMS Calcd for C29H37N4O10S2 [M-H+]:
665.1951. Found: 665.1955. Anal. Calcd for C29H38N4O10S2: C,
52.24%; N, 8.41%; H, 5.75%. Found: C, 52.59%; N, 8.29%; H, 5.86%.
20
N, 8.24%; H, 5.80%. [R]D ) +86.5° (c ) 1, CHCl3).
(1S,4S)-N,N′-Dibenzyloxycarbonyl-N′-(4,4-diethoxybutyl)-N-prop-
2-enyl-cyclopent-4-ene-1,3-diamine (22). This compound was prepared
from 170 mg (0.261 mmol) of 15 in 94% yield (135 mg, 0.245 mmol,
clear oil) by a procedure similar to that employed in the synthesis of
18. (For data, see Supporting Information.)
(2S,7S)-N-Benzyloxycarbonyl-2-[2-N-benzyloxycarbonyl-(4,4-di-
ethoxybutyl)amino]-but-3-enyl-2,5-dihydro-1H-pyrrole (23). This
compound was prepared from 100 mg (0.182 mmol) of 22 in 99%
yield (99 mg, 0.18 mmol) by a procedure similar to that employed in
20
[R]D ) +82.3° (c ) 1, CHCl3).
(1S,4S)-N-But-3-enyl-N,N′-dibenzyloxycarbonyl-N′-(4,4-diethoxy-
butyl)cyclopent-4-ene-1,3-diamine (18). 1.6 g (2.4 mmol) of 14 and
3.3 g (24 mmol) of K2CO3 were dissolved in dry DMF (30 mL) and
heated to 70 °C. 660 mg (6.0 mmol) of thiophenol was then added and
the solution stirred for 30 min. The mixture was cooled to room
temperature, and 1.0 g (6.0 mmol) of benzylchloroformiate, dissolved
in dry DMF (3 mL), was added. After an additional 10 min of stirring,
MTBE (100 mL) was added. The mixture was filtered, and the solvent
was removed under vacuum. The residue was chromatographed on silica
gel using MTBE/hexane (3:7) to yield 1.29 g (2.29 mmol, 95%) of 18
(clear oil). (For data, see Supporting Information.)
1
the synthesis of 19. H NMR (500 MHz, C6D6): δ ) 7.30-7.00 (m,
10 H, phenyl), 5.98-5.81 (m, 1 H), 5.60-5.50 (m, 1 H), 5.27 (m, 1
H), 5.20-5.05 (m, 5 H), 5.03-4.91 (m, 1 H), 4.72-4.53 (m, 1 H),
4.40 (t, 1 H, J ) 7 Hz), 4.03-3.86 (m, 1 H), 3.51 (m, 2 H), 3.35 (m,
2 H), 3.26-3.10 (m, 1 H), 2.04-1.88 (m, 1 H), 1.80-1.66 (m, 2 H),
1.58 (m, 2 H), 1.09 (t, 6 H, J ) 7 Hz). 13C NMR (C6D6): δ ) 155.6
(Cq, carbonyl), 154.2 (Cq, carbonyl), 137.7 (Cq, phenyl), 137.5 (Cq,
phenyl), 129.7 (CH), 128.3-127.5 (8 C), 125.1 (CH), 116.3 (CH2),
102.7 (CH), 66.8 (CH2), 60.7 (CH2), 56.9 (CH), 48.7 (CH), 45.3 (CH2),
31.4 (CH2), 26.8 (CH2), 25.3 (CH2), 15.2 (CH3). IR (film): 3065, 3032,