2230 J . Org. Chem., Vol. 63, No. 7, 1998
Takahata et al.
126.66, 128.28, 128.33; HRMS calcd for C25H47NO2Si2 449.3145,
found 449.3119.
isolated in 69.6% yield: [R]26D +4.13° (c 2.6, EtOH) [lit.15 [R]24
D
+4.5° (c 4.0, EtOH)]; IR (neat) 3346, 2932, 2823, 1215, 1151,
1110, 1044, 918 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.53 (2 H,
m), 1.97 (2 H, br s), 3.33-3.38 (6 H, m), 3.48-3.60 (4 H, m),
4.59-4.67 (4 H, m); 13C NMR (75 MHz, CDCl3) δ 28.12, 55.47,
57.15, 71.37, 96.81; HRMS C10H21NO4 (M+ - 1) 218.1392,
found 218.1397.
18: IR (neat) 2955, 2928, 2884, 2856, 1255, 1091, 836 cm-1
;
1H NMR (500 MHz, CDCl3) δ -0.041 (6H, s), -0.040 (6H, s),
0.85 (18 H, s), 1.60-1.61 (2 H, m), 1.83-1.86 (2 H, m), 2.87-
2.88 (2 H, br d), 3.24 (2 H, t, J ) 8.8 Hz), 3.37 (2 H, dd, J )
9.8, 4.7 Hz), 3.85 (2 H, s), 7.22-7.24 (1 H, m), 7.28-7.29 (2 H,
m), 7.31-7.34 (2 H, m); 13C NMR (125 MHz, CDCl3) δ -5.22,
-5.18, 18.45, 25.99, 26.12, 26.23, 27.63, 60.16, 67.12, 67.34,
126.94, 128.20, 129.29; HRMS calcd for C25H47NO2Si2 449.3145,
found 449.3113.
(2S,5S)-1c. The hydrogenolysis of (2S,5S)-20 was per-
formed on a 0.068 mmol scale as described in the typical
procedure (vide supra). The pyrrolidine (2S,5S)-1c was iso-
lated in 81% yield: [R]25 -4.2° (c 0.72, EtOH) [lit.15 [R]24
D
D
(2S,6S)-17 a n d (2S*,5R*)-18. The AD reaction was per-
formed on diene 4 (33.7 mmol) as described in the typical
-4.7° (c 4.1, EtOH)].
(2R,5R)- a n d (2R*,5S*)-N-Ben zyl-2,5-bis[[(ter t-bu tyl-
d ip h en ylsilyl)oxy]m eth yl]p yr r olid in es [(2R,5R)-17d ] a n d
[(2R*,5S*)-18d ]. To a solution of (2R,5R)-15d (1.16 g, 7.43
mmol) in DMF (12.3 mL) were added imidazole (1.14 g, 16.63
mmol) and tert-butyldiphenysilyl chloride (TBDPSCl). After
the mixture was stirred for 12 h, excess water and CH2Cl2 were
added. The organic layer was separated, and the aqueous
layer was extracted with CH2Cl2 three times. The combined
organic layers were successively washed with 20% KHSO4,
saturated NaHCO3, and brine. The organic layer was dried
and evaporated. The residue was chromatographed using
hexanes-ethyl acetate (5:1) as eluent to give a diastereomeric
mixture of (2R,5R)-16d (2.23 g, 47.9%) as an oil. By a
procedure similar to that for the preparation of 9 and 10,
(2R,5R)-16d (2.23 g, 3.56 mmol) was converted in a two-step
sequence [(1) p-toluenesulfonyl chloride (1.59 g, 8.9 mmol),
triethylamine (1.20 mL, 8.9 mmol), DMAP (84.5 mg, 0.71
mmol) in CH2Cl2 (4.6 mL); (2) benzylamine (9.1 mL, 1.68
mmol)] to (2R,5R)-17d (1.15 g, 59.4%) and (2R*,5S*)-18d
(0.584 g, 30.1%) as an oils. (2R,5R)-17d : [R]25D +36.8 (c 1.035,
CHCl3); IR (neat) 3071, 2930, 1472, 1428, 1112, 823, 738, 699
procedure (vide supra) using (DHQD)2-PYR as ligand.
A
diastereomeric mixture of tetra-15 was isolated in 63.6% yield.
By a procedure similar to that for the preparation of (2R,5R)-
17 and (2R*,5S*)-18, (2S,6S)-17 and (2S*,5R*)-18 were ob-
tained in 25% and 5.3% yields, respectively. (2S,6S)-17: [R]25
D
-48.1° (c 1.78, CHCl3).
(2R ,5R )-N -B e n zy l-2,5-b is (h y d r o x y m e t h y l)p y r r o li-
d in es [(2R,5R)-19]. The de-tert-butyldimethylsilylation of
(2R,5R)-17 was performed on a 0.283 mmol scale as described
in the typical procedure (vide supra). Diol (2R,5R)-19 was
isolated in 92.9% yield: [R]25 +56.6° (c 1.69, MeOH) [lit.16
D
[R]25 +49.2° (c 0.5, MeOH)]; IR (neat) cm-1
;
1H NMR (500
D
MHz, CDCl3) δ 1.79-1.84 (2 H, m), 1.98-2.06 (4 H, m), 3.18-
3.21 (2 H, m), 3.55 (2 H, dd, J ) 10.9, 2.8 Hz), 3.63 (2 H, dd,
J ) 10.9, 4.7 Hz), 3.88 (2 H, s), 7.25-7.27 (1 H, m), 7.27-7.28
(2 H, m), 7.32-7.37 (2 H, m); 13C NMR (125 MHz, CDCl3) δ
21.17, 51.71, 61.95, 62.17, 76.94, 77.20, 77.45, 127.21, 128.29,
128.64, 139.66. The ee of (2R,5R)-19 was determined by HPLC
analysis (Daicel Chiralpak AD, 10% i-PrOH/hexane, 0.7 mL/
min) to be 82%.
1
(2S,5S)-19. By a procedure similar to that for the prepara-
tion of (2R,5R)-19, the hydrolysis of (2S,5S)-17 was performed
on a 0.156 mmol scale. The pyrrolidine (2S,5S)-19 was
cm-1; H NMR (500 MHz, CDCl3) δ 1.10 (18 H, s), 1.83-1.87
(2 H, m), 2.08-2.13 (2 H, m), 3.22-3.23 (2 H, d, J ) 4.9 Hz),
3.58-3.62 (4 H, m), 3.77, 3.97 (each 1 H, ABq, J ) 14.5 Hz),
7.16-7.23 (8 H, m), 7.38-7.49 (12 H, m), 7.66-7.73 (5 H, m);
13C NMR (125 MHz, CDCl3) δ 19.37, 27.08, 27.40, 52.70, 62.65,
65.76, 126.47, 127.78, 127.80, 128.14, 128.21, 129.75, 133.95,
134.00, 135.80, 135.88, 140.94; HRMS calcd for C45H55NO2Si2
(M+) 698.1082, found 698.1063.
obtained in 67% yield: [R]25D -62.3° (c 0.8, MeOH) [lit.17 [R]25
D
-70.3° (c 0.5, MeOH)]; 88% ee.
(2R,5R)-N-Ben zyl-2,5-bis[(m eth oxym eth oxy)m eth yl]pyr -
r olid in es [(2R,5R)-20]. The methoxymethylation of (2R,5R)-
19 was performed on a 0.648 mmol scale by a procedure similar
to that for the preparation of (2R,6R)-14. Compound (2R,5R)-
18d : IR (neat) 3070, 2930, 2857, 1472, 1428, 1389, 1112,
1
20 was isolated in 57.0% yield: [R]25 +42.8° (c 5.19, CHCl3);
824, 739, 700 cm-1; H NMR (500 MHz, CDCl3) δ 1.00 (18 H,
D
IR (neat) cm-1; 1H NMR (500 MHz, CDCl3) δ 1.70-1.76 (2 H,
m), 2.03-2.08 (2 H, m), 3.20-3.29 (2 H, m), 3.35 (6 H, s), 3.45
(2 H, dd, J ) 9.8, 6.1 Hz), 3.51 (2 H, dd, J ) 9.8, 4.3 Hz), 3.89,
4.05 (each 1 H, ABq, J ) 14.3 Hz), 4.59 (4 H, s), 7.23 (1 H, t,
s), 1.65-1.70 (2 H, m), 1.86-1.90 (2 H, m), 2.98-3.01 (2 H,
m), 3.31-3.34 (2 H, dd, J ) 9.8, 7.7 Hz), 3.45-3.48 (2 H, m),
3.78 (2 H, s), 7.16 (5 H, s), 7.28-7.43 (12 H, m), 7.58-7.62 (8
H, m); 13C NMR (125 MHz, CDCl3) δ 19.39, 27.02, 27.78, 59.57,
66.60, 67.97, 126.77, 127.71, 128.09, 129.24, 129.59, 134.11,
135.72, 135.74, 140.36; HRMS calcd for C45H55NO2Si2 (M+)
698.1082, found 698.1111.
J ) 7.3 Hz), 7.28-7.32 (2 H, m), 7.38 (2 H, d, J ) 7.3 Hz); 13
C
NMR (125 MHz, CDCl3) δ 27.61, 52.83, 55.44, 60.60, 69.55,
96.82, 16.69, 128.22, 128.27, 140.62. Anal. Calcd for C17H27
NO4: C, 65.99; H, 8.80; N, 4.53. C, 66.08; H, 8.99; N, 4.31.
-
(2S,5S)-17d a n d (2S*,5R*)-18d . By a procedure similar
to that for the preparation of (2R,5R)-17d and (2R*,5S*)-18d ,
the pyrrolidines (2S,5S)-17d and (2S*,5R*)-18d were obtained
in 19% and 6.9% yields, respectively, from (2S,5S)-15d (9.34
(2S,5S)-20. By a procedure similar to that for the prepara-
tion of (2R,5R)-20, the methoxymethylation of (2S,5S)-19 was
performed on a 0.150 mmol scale. The pyrrolidine (2S,5S)-20
was obtained in 49% yield: [R]25 -46.9° (c 1.13, CHCl3).
mmol). (2S,5S)-17d : [R]25 -40.1 (c 1.035, CHCl3).
D
D
(2R,5R)-2,5-Bis[[(ter t-bu tyld im eth ylsilyl)oxy]m eth yl]-
p yr r olid in es [(2R,5R)-1a ]. The hydrogenolysis of (2R,5R)-
17 was performed on a 0.218 mmol scale as described in the
typical procedure (vide supra). The pyrrolidine (2R,5R)-1a was
(2S,5S)-1d . The hydrogenolysis of (2S,5S)-17d was per-
formed on a 0.058 mmol scale as described in the typical
procedure (vide supra). The pyrrolidine (2S,5S)-1d was
isolated in 96% yield: [R]25 -6.8° (c 1.41, EtOH); IR (neat)
D
isolated in 54% yield: [R]25 +6.3° (c 2.3, CHCl3); IR (neat)
3342, 2930, 2857, 1427, 1111, 700 cm-1; H NMR (500 MHz,
1
D
3363, 2955, 2929, 2857, 1472, 1463, 1256, 1094, 837, 775 cm-1
;
CDCl3) δ 1.07 (18H, s), 1.47-1.48 (2 H, m), 1.84-1.86 (2 H,
m), 3.34-3.41 (1 H, m), 3.47-3.53 (2 H, m), 3.56 (2 H, d, J )
6.6 Hz), 3.64-3.70 (1 H, m), 7.39-7.49 (12 H, m), 7.67-7.71
(8 H, m); 13C NMR (125 MHz, CDCl3) δ 19.37, 19.45, 27.00,
27.05, 27.12, 27.36, 58.86, 60.62, 66.66, 67.37, 72.95, 127.84,
127.92, 127.93, 129.78, 129.95, 133.33, 133.87, 135.76, 135.82;
HRMS calcd for C38H49NO2Si2 (M+) 607.3302, found 607.3275.
(2R,6R)- a n d (2R*,6S*)-N-Ben zyl-2,6-bis[[(ter t-bu tyl-
d ip h en ylsilyl)oxy]m eth yl]-3-oxa p ip er id in es [(2R,6R)-22]
a n d [(2R*,6S*)-23]. The AD reaction was performed on the
allyl ether 6 (7 mmol) as described in the typical procedure
(vide supra) using (DHQ)2-AQN as ligand. By a procedure
similar to that for the preparation of 9 and 10, a diastereomeric
mixture of tetrol 21 (7 mmol) was converted in a three-step
sequence [(1) imidazole (1.05 g, 15.4 mmol), TBDPSCl (3.45
1H NMR (500 MHz, CDCl3) δ -0.03-0.05 (12 H, m), 0.78-
1.03 (18H, m), 1.48-1.55 (2 H, m), 1.87-1.95 (2 H, m), 2.20 (1
H, s), 3.36-3.42 (2 H, m), 3.46-3.63 (4 H, m); 13C NMR (125
MHz, CDCl3) δ -5.07, -4.98, 18.59, 26.21, 27.48, 27.62, 59.07,
65.06, 65.29, 66.68; HRMS calcd for C18H41NO2Si 359.2675,
found 359.2651.
(2S,5S)-1a . The hydrogenolysis of (2S,5S)-17 was per-
formed on a 0.124 mmol scale as described in the typical
procedure (vide supra). The pyrrolidine (2S,5S)-1a was iso-
lated in 95% yield: [R]25 -6.5° (c 1.8, CHCl3).
D
(2R ,5R )-2,5-Bis[(m e t h oxym e t h oxy)m e t h yl]p yr r oli-
d in es [(2R,5R)-1c]. The hydrogenolysis of (2R,5R)-20 was
performed on a 0.343 mmol scale as described in the typical
procedure (vide supra). The pyrrolidine (2R,5R)-1c was