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F. A. Davis, J. Deng / Tetrahedron 60 (2004) 5111–5115
one-necked, round-bottomed flask equipped with a mag-
netic stirring bar, rubber septum, and argon-filled balloon
was placed (RS,5S)-(2)-5 (0.170 g, 0.40 mmol) in MeOH
(8 mL). The reaction mixture was cooled to 0 8C, TFA
(0.156 mL, 2.0 mmol) was added, and the reaction mixture
was stirred at rt for 2 h. At this time the solution was
concentrated, the residue was dissolved in THF (8 mL),
cooled to 0 8C, and Et3N (0.330 mL, 2.4 mmol), DMAP (ca.
0.005 g), and di-tert-butyldicarbonate (0.132 g (0.60 mmol)
were added. The reaction mixture was stirred for 2 h at 0 8C
and quenched by the addition of sat. NH4Cl (3.0 mL). The
aqueous phase was extracted with EtOAc (2£8 mL), and the
combined organic phases were washed with H2O (8 mL),
brine (8 mL), dried (Na2SO4), and concentrated. Chroma-
tography (5–30% EtOAc/hexanes) gave 0.130 g (86%) of a
yellow solid; mp 57.0–58.0 8C; [a]2D0¼þ3.60 (c 0.7,
1H NMR (CHCl3) d 0.87 (t, J¼7.0 Hz, 3H), 1.24 (m, 4H),
1.38 (m, 2H), 1.43 (s, 9H), 2.05 (dd, J¼7.5, 15.0 Hz, 2H),
2.86 (d, J¼5.0 Hz, 2H), 3.46 (dd, J¼20.0, 16.0 Hz, 2H),
3.73 (s, 3H), 4.50 (m, 1H), 5.01 (bs, 1H), 5.53 (dd, J¼8.0,
16.5 Hz, 1H), 5.69 (m, 1H), 5.98 (m, 1H), 6.12 (dd, J¼10.5,
15.0 Hz, 1H); 13C NMR d 14.4, 23.0, 29.0, 29.4, 32.0, 33.0,
48.4, 49.5, 50.0, 52.8, 80.2, 91.7, 129.8, 129.9, 132.2, 136.5,
155.7, 167.8, 201.1. Anal calcd for C21H37NO5: C, 65.77; H,
9.72; N, 3.65. Found: C, 65.55; H, 9.29; N, 3.72.
52.6, 76.9, 79.6, 156.0, 162.3, 191.3. HR-MS calcd for
C20H35NO5Na (MþNa): 420.2474. Found: 420.2468.
2.1.7. Methyl-N-(tert-butyloxycarbonyl)-3-oxo-5-nonyl-
pyrrolidine-2-carboxylate (9). In a 50-mL, one-necked,
round-bottomed flask equipped with a magnetic stirring bar
and argon-filled balloon was placed (S)-(þ)-8 (0.250 g,
0.63 mmol) in DCM (20 mL). To the solution was added
Rh2(OAc)4 (0.028, 5 mol%) and the reaction mixture was
stirred for 2 h at rt. At this time, the solution was
1
concentrated. The H NMR spectra indicated the presence
of a single isomer as a mixture of rotomers suggested by
1
peak broadening; major rotomer: H NMR (CHCl3) d 0.87
(t, J¼7.0 Hz, 3H), 1.29 (m, 24H), 1.95 (b, 1H), 2.40 (b, 1H),
2.80 (b, 1H), 3.80 (s, 3H), 4.28 (b, 1H), 4.60 (b, 1H); minor
rotomer: d 0.87 (t, J¼7.0 Hz, 3H), 1.29 (m, 24H), 1.95 (b,
1H), 2.38 (b, 1H), 2.82 (b, 1H), 3.80 (s, 3H), 4.28 (b, 1H),
4.68 (b, 1H). Chromatography (10% EtOAc/hexanes)
resulted in a 6:1 mixture of isomers; major isomer: 1H
NMR (CHCl3) d 0.87 (t, J¼7.0 Hz, 3H), 1.29 (m, 24H), 1.95
(b, 1H), 2.40 (b, 1H), 2.80 (b, 1H), 3.80 (s, 3H), 4.28 (b, 1H),
4.60 (b, 1H); minor isomer: d 0.87 (t, J¼7.0 Hz, 3H), 1.29
(m, 24H), 1.82 (b, 1H), 2.38 (b, 1H), 2.90 (b, 1H), 3.76 (s,
3H), 4.40 (b, 1H), 4.60 (b, 1H).
CHCl3); IR (KBr): 3349, 2924, 1751, 1684, 1525 cm21
;
2.1.8. (2S,3S,5R)-(2)-N-Methyl-2-hydroxymethyl-3-
hydroxy-5-nonylpyrrolidine (10). To crude 9 was added
THF (20 mL), the solution was cooled to 278 8C, LAH
(0.120 g, 3.15 mmol) was added, and the reaction mixture
was stirred for 4 h. At this time, the solution was slowly
warmed to 0 8C, stirred at this temperature for 2 h, cooled to
278 8C, and LAH (0.120 g, 3.15 mmol) was added. The
reaction mixture was heated at 70 8C for 72 h at which time
the reaction was quenched by the addition of H2O (0.24 mL)
and 10% NaOH (0.72 mL), and H2O (0.24 mL). The
solution was stirred for 1 h, passed through Celite, the
organic phase was washed with brine (5 mL), and (Na2SO4),
and concentrated. Chromatography (2% MeOH/EtOAc)
afforded 0.099 g (61%) of an oil [a]2D0¼237.8 (c 0.7,
CHCl3); IR (KBr): 3379, 2925, 2854, 2791, 1030 cm21; 1H
NMR (CHCl3) d 0.87 (t, J¼7.0 Hz, 3H), 1.29 (b, 16H), 1.41
(b, 9H), 1.70 (m, 1H), 2.25 (m, 1H), 2.27 (s, 3H), 2.39 (m,
1H), 2.44 (m, 1H), 3.11 (b, 2H), 3.73 (dd, J¼3.5, 11.5 Hz,
1H), 3.80 (dd, J¼2.0, 11.5 Hz, 1H), 4.29 (dd, J¼7.0,
14.0 Hz, 1H); 13C NMR d 14.5, 23.1, 26.5, 29.7, 29.98,
30.02, 30.4, 32.3, 34.1, 39.0, 42.3, 59.5, 64.4, 70.1, 72.3.
HR-MS calcd for C15H31NO2Na (MþNa): 280.2252.
Found: 280.2260.
2.1.5. (S)-(1)-Methyl-3-oxo-5-(tert-butyloxycarbonyl-
amino)-5-nonylpentanoate (7). In a 50-mL, one-necked,
round-bottomed flask equipped with a magnetic stirring bar
and rubber septum was placed (S)-(þ)-6 (0.40 g,
1.04 mmol) in MeOH (20 mL). To the solution was added
10% Pd/C and the reaction mixture was stirred under an H2
balloon for 2 h. At this time, the solution was filtered
through Celite and concentrated to give 0.404 g (100%) of a
white solid; mp 48.0–49.0 8C; [a]2D0¼þ27.2 (c 1.1, CHCl3);
IR (KBr): 3353, 2923, 1684 cm21; 1H NMR (CHCl3) d 0.87
(t, J¼7.0 Hz, 3H), 1.24 (b, 14H), 1.41 (b, 9H), 1.50 (b, 2H),
2.74 (m, 2H), 3.47 (m, 2H), 3.73 (s, 3H), 3.89 (m, 1H), 4.79
(d, J¼8.0 Hz, 1H); 13C NMR d 14.5, 23.1, 26.6, 28.8, 29.7,
29.9, 32.3, 35.0, 47.8, 48.0, 49.7, 52.8, 79.7, 91.4, 155.8,
167.9, 202.2. Anal calcd for C21H41NO5: C, 65.08; H,
10.66; N, 3.61. Found: C 64.83; H, 10.24; N, 4.01.
2.1.6. (S)-(1)-Methyl-2-diazo-3-oxo-5-(tert-butyloxy-
carbonylamino)-5-nonylpentanoate (8). In a 25-mL,
one-necked, round-bottomed flask equipped with a mag-
netic stirring bar, rubber septum, and argon balloon was
placed (S)-(þ)-7 (0.400 g, 1.08 mmol) and p-carboxy-
benzenesulfonyl azide (p-CBSA) (0.277 g, 1.18 mmol) in
acetonitrile (8 mL). The reaction mixture was cooled to 0 8C
and Et3N (0.44 mL, 3.24 mmol) was added and the reaction
mixture was stirred for 2 h. At this time, the white
precipitate was removed by filtration, the filtrate was
concentrated, and EtOAc (20 mL) was added to the residue.
The organic phase was washed with H2O (2£8 mL), 1 N
NaOH (2£8 mL), brine (10 mL), dried (Na2SO4), and
concentrated to give 0.400 g (94%) of a gel; [a]2D0¼þ26.4
(c 1.0, CHCl3); IR (KBr): 3376, 2928, 2855, 2135, 1718,
2.1.9. (2S,3S,5R)-(1)-Preussin (2). In a 10-mL, one-
necked, round-bottomed flask equipped with a magnetic
stirring bar, rubber septum, and argon balloon was placed
(2)-10 (0.031 g, 0.120 mmol) in DCM (5 mL), the solution
was cooled to 0 8C, Ph3P (0.160 g, 0.60 mmol), imidazole
(0.041 g, 0.60 mmol), and I2 (0.150 g, 0.60 mmol) were
added. The reaction mixture was stirred at this temperature
for 4 h and the solution was filtered. The filtrate was
concentrated, dissolved in THF (3 mL), and cooled to
278 8C. In a separate 10-mL, one-necked, round-bottomed
flask equipped with a magnetic stirring bar, rubber septum,
and argon balloon was placed CuI (0.230 g, 1.20 mmol) in
THF (2 mL). The solution was cooled to 0 8C, and PhLi
(1.5 mL, 2.40 mmol, 1.6 M in cyclohexane and ether) was
1
1172 cm21; H NMR (CHCl3) d 0.87 (t, J¼7.0 Hz, 3H),
1.24 (b, 14H), 1.41 (b, 9H), 1.50 (b, 2H), 3.00 (m, 2H), 3.73
(s, 3H), 3.89 (m, 1H), 4.79 (d, J¼8.0 Hz, 1H); 13C NMR d
14.5, 23.1, 26.6, 29.8, 29.9, 30.0, 32.4, 36.1, 45.7, 49.0,