2998 J. Am. Chem. Soc., Vol. 122, No. 13, 2000
Takahashi et al.
4.62-4.52 (m, 4 H), 4.51 (d, J ) 10.0 Hz, 1 H), 4.48 (d, J ) 11.9 Hz,
1 H), 4.33 (d, J ) 3.66 Hz, 1 H), 4.07 (dd, J ) 3.66 Hz, J ) 2.14 Hz,
1 H), 3.94-3.89 (m, 1 H), 3.85 (dd, J ) 5.80 Hz, J ) 5.49 Hz, 1 H),
3.66-3.62 (m, 1 H), 3.63 (s, 3 H), 3.57 (dd, J ) 5.19 Hz, J ) 4.58
Hz, 1 H), 2.83 (d, J ) 4.27 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ
168.65, 138.03, 137.95, 137.50, 136.59, 128.62, 128.40, 128.36, 128.32,
128.29, 127.99, 127.85, 127.82, 127.69, 127.65, 80.44, 79.45, 77.41,
75.30, 74.11, 73.96, 73.37, 71.25, 70.98, 64.27; IR (neat, cm-1) 1736,
1686; HRMS (EI) exact mass calcd for C35H39NO7 (M+) 585.2726,
1N-Benzyloxy-3-phenylpropanamide (8): 1H NMR (400 MHz,
CDCl3) δ 7.70 (brs, 1 H), 7.35-7.14 (m, 10 H), 4.79 (brs, 2 H), 2.96
(m, 2 H), 2.34 (brs, 2 H); 13C NMR (100 MHz, CDCl3) δ 169.66,
140.30, 135.24, 129.21, 128.55, 128.38(m), 128.71, 126.34, 78.14,
35.03, 31.23; IR (KBr, cm-1) 1651; HRMS (EI) exact mass calcd for
C16H17NO2 (M+) 255.1259, found 255.1255; mp 81 °C.
General Procedure for Cyclization of δ-Hydroxyalkoxamates.
A mixture of 4a (504 mg, 0.76 mmol), triphenylphosphine (594 mg,
2.27 mmol), and DEAD (0.36 mL, 2.27 mmol) in 7.6 mL of THF was
stirred at room temperature for 10 min. The solvent was removed in
vacuo. The residue was chromatographed on silica gel (hexane/AcOEt
) 7:1) to give 346 mg (71%) of 11a and 63 mg (13%) of 14a.
2N-Benzyloxy-3,4,5-tris(benzyloxy)-6-benzyloxymethyl-(3R,4S,
5R,6S)-tetrahydro-2H-pyran-2-imine (11a): 1H NMR (400 MHz,
CDCl3) δ 7.40 (m, 2 H), 7.30-7.20 (m, 23 H), 5.08 (s, 2 H), 4.71 (d,
J ) 11.60 Hz, 1 H), 4.59 (d, J ) 11.60 Hz, 1 H), 4.58 (d, J ) 11.60
Hz, 1 H), 4.54 (d, J ) 11.90 Hz, 1 H), 4.50-4.45 (m, 3 H), 4.40 (d,
J ) 11.90 Hz, 1 H), 4.38 (d, J ) 11.90 Hz, 1 H), 4.08 (d, J ) 5.19 Hz,
1 H), 3.88-3.82 (m, 2 H), 3.76 (dd, J ) 5.80 Hz, J ) 4.28 Hz, 1 H),
3.72 (dd, J ) 3.36 Hz, J ) 2.75 Hz, 1 H); 13C NMR (100 MHz, CDCl3)
δ 149.98, 138.46, 137.94, 137.64, 137.60, 137.53, 128.41, 128.35,
128.33, 128.28, 128.18, 127.99, 127.85, 127.79, 127.71, 127.65, 127.58,
78.16, 76.24, 76.06, 75.20, 74.92, 73.44, 72.48, 71.91, 71.86, 68.11;
IR (KBr, cm-1) 1657; HRMS (FAB) exact mass calcd for C41H42NO6
found 585.2727; [R]24 +28.3° (c 0.74, CHCl3).
D
1N-Ethoxy-2,3,4,6-tetrakis(benzyloxy)-5-hydroxy-(2R,3S,4R,5R)-
hexanamide (4c): 1H NMR (400 MHz, CDCl3) δ 8.93 (s, 1 H), 7.35-
7.21 (m, 20 H), 4.70 (d, J ) 11.30 Hz, 1 H), 4.69 (d, J ) 11.00 Hz,
1 H), 4.60-4.48 (m, 6 H), 4.32 (d, J ) 3.66 Hz, 1 H), 4.07 (dd, J )
3.66 Hz, J ) 1.83 Hz, 1 H), 3.95-3.89 (m, 1 H), 3.87-3.79 (m, 3 H),
3.65 (dd, J ) 6.71 Hz, J ) 3.05 Hz, 1 H), 3.58 (dd, J ) 6.71 Hz, J )
3.05 Hz, 1 H), 2.80 (d, J ) 4.27 Hz, 1 H), 1.19 (dd, J ) 7.02 Hz, J )
7.01 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 168.70, 138.06, 137.99,
137.55, 136.64, 128.65, 128.45, 128.39, 128.33, 128.05, 127.99, 127.95,
127.86, 127.80, 127.72, 127.69, 80.45, 79.49, 77.43, 75.33, 74.11, 73.96,
73.42, 72.18, 71.24, 71.02, 13.39; IR (neat, cm-1) 1684; HRMS (EI)
exact mass calcd for C36H41NO7 (M+) 599.2883, found 599.2886; [R]24
D
+33.0° (c 1.54, CHCl3).
1N-tert-Butoxy-2,3,4,6-tetrakis(benzyloxy)-5-hydroxy-(2R,3S,4R,5R)-
hexanamide (4d): 1H NMR (400 MHz, CDCl3) δ 8.56 (s, 1 H), 7.32-
7.23 (m, 20 H), 4.71 (d, J ) 10.90 Hz, 1 H), 4.68 (d, J ) 10.90 Hz,
1 H), 4.65 (d, J ) 11.20 Hz, 1 H), 4.58 (d, J ) 11.20 Hz, 1 H), 4.57
(d, J ) 11.20 Hz, 1 H), 4.54 (d, J ) 11.90 Hz, 1 H), 4.52 (d, J )
11.20 Hz, 1 H), 4.48 (d, J ) 11.90 Hz, 1 H), 4.34 (d, J ) 3.66 Hz, 1
H), 4.07 (dd, J ) 3.66 Hz, J ) 2.14 Hz, 1 H), 3.93-3.88 (m, 1 H),
3.86 (dd, J ) 5.49 Hz, J ) 2.14 Hz, 1 H), 3.64 (dd, J ) 6.14 Hz, J )
3.05 Hz, 1 H), 3.58 (dd, J ) 6.14 Hz, J ) 3.05 Hz, 1 H), 2.82 (d, J )
3.66 Hz, 1 H), 1.24 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 169.76,
138.03, 137.94, 137.50, 136.57, 128.56, 128.50, 128.29, 128.25, 128.23,
127.95, 127.79, 127.76, 127.61, 127.57, 81.70, 80.59, 79.68, 77.47,
75.39, 74.02, 73.82, 73.29, 71.10, 70.91, 26.23; IR (neat, cm-1) 1699;
HRMS (EI) exact mass calcd for C38H45NO7 (M+) 627.3196, found
(M + H)+ 644.3012, found 644.3011; mp 65 °C; [R]24 +30.6° (c
D
1.03, CHCl3). Anal. Calcd for C41H41NO6: C, 76.49; H, 6.42; N, 2.18.
Found: C, 76.29; H, 6.54; N, 2.16.
2N-Methoxy-3,4,5-tris(benzyloxy)-6-benzyloxymethyl-(3R,4S,
5R,6S)-tetrahydro-2H-pyran-2-imine (11b): 1H NMR (400 MHz,
CDCl3) δ 7.39-7.20 (m, 20 H), 4.92 (d, J ) 11.90 Hz, 1 H), 4.57 (m,
2 H), 4.54 (d, J ) 11.90 Hz, 1 H), 4.50 (d, J ) 11.90 Hz, 1 H), 4.48-
4.45 (m, 3 H), 4.40 (d, J ) 11.90 Hz, 1 H), 4.16 (d, J ) 5.49 Hz, 1 H),
3.89-3.86 (m, 4 H), 3.83 (dd, J ) 6.11 Hz, J ) 3.66 Hz, 1 H), 3.77-
3.72 (m, 2 H); 13C NMR (100 MHz, CDCl3) δ 149.61, 137.86, 137.63,
137.59, 137.48, 128.40, 128.32, 128.30, 127.98, 127.85, 127.81, 127.77,
127.67, 78.29, 75.85, 75.11, 73.44, 72.42, 72.22, 71.74, 67.95, 62.59;
IR (neat, cm-1) 1657; HRMS (EI) exact mass calcd for C35H37NO6
(M+) 567.2621, found 567.2617; [R]24D +33.8° (c 1.11, CHCl3). Anal.
Calcd for C35H37NO6: C, 74.05; H, 6.57; N, 2.47. Found: C, 74.30;
H, 6.34; N, 2.36.
627.3194; [R]24 +30.6° (c 1.00, CHCl3).
D
1N-Benzyloxy-2,3,4,6-tetrakis(benzyloxy)-5-hydroxy-(2R,3S,4S,5R)-
hexanamide (5): 1H NMR (400 MHz, CDCl3) δ 8.89 (br, 1 H), 7.33-
7.20 (m, 21 H), 7.16 (m, 2 H), 7.03 (m, 2 H), 4.90 (m, 2 H), 4.67 (d,
J ) 10.68 Hz, 1 H), 4.56 (d, J ) 10.68 Hz, 1 H), 4.53 (d, J ) 12.21
Hz, 1 H), 4.45 (d, J ) 12.21 Hz, 1 H), 4.43 (d, J ) 11.60 Hz, 1 H),
4.35 (d, J ) 10.99 Hz, 1 H), 4.33 (d, J ) 11.60 Hz, 1 H), 4.24 (d, J
) 2.14 Hz, 1 H), 4.22 (d, J ) 10.99 Hz, 1 H), 4.15 (dd, J ) 8.24 Hz,
J ) 2.14 Hz, 1 H), 4.09 (ddd, J ) 6.41 Hz, J ) 6.41 Hz, J ) 1.46 Hz,
1 H), 3.82 (dd, J ) 8.24 Hz, J ) 1.46 Hz, 1 H), 3.57 (dd, J ) 9.46 Hz,
J ) 6.41 Hz, 1 H), 3.49 (dd, J ) 9.46 Hz, J ) 6.41 Hz, 1 H), 2.45 (d.
J ) 8.24 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 168.91, 137.92,
137.84, 137.49, 136.36, 135.24, 128.85, 128.74, 128.67, 128.52, 128.40,
128.22, 128.18, 127.91, 127.81, 127.72, 127.34, 79.85, 79.19, 78.27,
77.04, 75.24, 73.69, 73.36, 73.28, 71.28, 69.21; IR (neat, cm-1) 1748,
1698; HRMS (FAB) exact mass calcd for C41H43NO7Na 684.2975 (M
2N-Ethoxy-3,4,5-tris(benzyloxy)-6-benzyloxymethyl-(3R,4S,5R,6S)-
1
tetrahydro-2H-pyran-2-imine (11c): H NMR (400 MHz, CDCl3) δ
7.40-7.21 (m, 20 H), 4.90 (d, J ) 11.60 Hz, 1 H), 4.60 (d, J ) 11.90
Hz, 1 H), 4.59 (d, J ) 11.60 Hz, 1 H), 4.55 (d, J ) 12.21 Hz, 1 H),
4.52-4.46 (m, 4 H), 4.42 (d, J ) 11.9 Hz, 1 H), 4.15-4.09 (m, 3 H),
3.89 (dd, J ) 5.18 Hz, J ) 3.66 Hz, 1 H), 3.85 (dd, J ) 5.80 Hz, J )
3.97 Hz, 1 H), 3.78 (dd, J ) 5.80 Hz, J ) 4.27 Hz, 1 H), 3.74 (dd, J
) 3.66 Hz, J ) 3.05 Hz, 1 H), 1.31 (dd, J ) 7.02 Hz, J ) 7.02 Hz,
3 H); 13C NMR (100 MHz, CDCl3) δ 149.34, 137.93, 137.70, 137.64,
137.55, 128.37, 128.29, 128.26, 127.91, 127.81, 127.76, 127.73, 127.61,
78.23, 75.87, 75.17, 75.12, 73.39, 72.45, 72.08, 71.82, 69.98, 68.00,
14.64; IR (neat, cm-1) 1657; HRMS (EI) exact mass calcd for C36H39-
NO6 (M+) 581.2777, found 581.2775; [R]24D +35.5° (c 1.00, CHCl3).
2N-tert-Butoxy-3,4,5-tris(benzyloxy)-6-benzyloxymethyl-(3R,
+ Na)+, found 684.2956; [R]24 +45.6° (c 1.29, CHCl3).
1
D
4S,5R,6S)-tetrahydro-2H-pyran-2-imine (11d): H NMR (400 MHz,
1N-Benzyloxy-2,3,4,6-tetrakis(benzyloxy)-5-hydroxy-(2S,3S,4R,5R)-
hexanamide (6): 1H NMR (400 MHz, CDCl3) δ 8.89 (s, 1 H), 7.35-
7.15 (m, 25 H), 4.85 (d, J ) 11.30 Hz, 1 H), 4.79 (d, J ) 11.60 Hz,
1 H), 4.66 (s, 2 H), 4.54 (d, J ) 11.30 Hz, 1 H), 4.52 (d, J ) 11.60
Hz, 1 H), 4.51-4.46 (m, 2 H), 4.45 (d, J ) 11.00 Hz, 1 H), 4.36 (d,
J ) 11.60 Hz, 1 H), 4.25 (d, J ) 3.30 Hz, 1 H), 4.10 (dd, J ) 4.28 Hz,
J ) 4.27 Hz, 1 H), 3.97 (m, 1 H), 3.82 (dd, J ) 5.18 Hz, J ) 2.14 Hz,
1 H), 3.61 (m, 2 H), 2.94 (d, J ) 6.10 Hz, 1 H); 13C NMR (100 MHz,
CDCl3) δ 168.00, 138.03, 137.95, 137.88, 136.85, 135.26, 128.99,
128.59, 128.49, 128.44, 128.38, 128.34, 128.30, 128.26, 128.19, 128.08,
128.02, 127.98, 127.83, 127.79, 127.71, 127.64, 80.85, 79.48, 78.71,
78.18, 74.75, 74.26, 73.40, 72.53, 71.04, 70.72; IR (KBr, cm-1) 1698;
HRMS (FAB) exact mass calcd for C41H43NO7Na (M + Na)+ 684.2937,
found 684.2936; mp 79 °C; [R]22D +5.83° (c 1.10, CHCl3). Anal. Calcd
for C41H43NO7: C, 74.41; H, 6.55; N, 2.12. Found: C, 74.34; H, 6.58;
N, 2.05.
CDCl3) δ 7.40-7.22 (m, 20 H), 4.90 (d, J ) 11.60 Hz, 1 H), 4.65-
4.57 (m, 3 H), 4.56-4.46 (m, 5 H), 4.12 (d, J ) 5.19 Hz, 1 H), 3.91
(dd, J ) 5.19 Hz, J ) 4.27 Hz, 1 H), 3.87 (dd, J ) 6.10 Hz, J ) 3.97
Hz, 1 H), 3.80 (dd, J ) 5.49 Hz, J ) 5.19 Hz, 1 H), 3.75 (dd, J ) 4.27
Hz, J ) 3.35 Hz, 1 H), 1.33 (s, 9 H); 13C NMR (100 MHz, CDCl3) δ
148.22, 138.11, 137.93, 137.80, 137.71, 128.33, 128.26, 128.24, 127.78,
127.75, 127.72, 127.68, 127.65, 78.30, 78.27, 75.88, 75.38, 75.23, 73.36,
72.60, 71.95, 71.84, 68.25, 27.44; IR (neat, cm-1) 1665; HRMS (EI)
exact mass calcd for C38H43NO6 (M+) 609.3090, found 609.3092; [R]24
D
+28.6° (c 0.99, CHCl3).
2N-Benzyloxy-3,4,5-tris(benzyloxy)-6-benzyloxymethyl-(3R,4S,
5S,6S)-tetrahydro-2H-pyran-2-imine (12): 1H NMR (400 MHz,
CDCl3) δ 7.40-7.38 (m, 2 H), 7.32-7.19 (m, 21 H), 7.14-7.11 (m,
2 H), 5.12 (d, J ) 12.80 Hz, 1 H), 5.07 (d, J ) 12.80 Hz, 1 H), 4.68
(d, J ) 11.90 Hz, 1 H), 4.63 (d, J ) 12.20 Hz, 1 H), 4.56 (d, J )
12.20 Hz, 1 H), 4.54 (d, J ) 12.20 Hz, 1 H), 4.52-4.47 (m, 3 H), 4.44