3650
S. M. Clark, H. M. I. Osborn / Tetrahedron: Asymmetry 15 (2004) 3643–3652
20
Compound 5e: ½a ¼ þ72:0 (c 1.0, CHCl3); mmax (NaCl
4.14. (2R)-[(2S,6S)-2-(tertButyldiphenylsilanyloxy-
methyl)-6-methoxy-morpholin-4-yl]-3-phenyl-propionic
acid methyl ester 5f and (2R)-[(2S,6R,7S)-2-(tertbutyldi-
phenylsilanyloxymethyl)-6-hydroxy-7-methoxy-[1,4]-oxa-
zepan-4-yl]-3-phenyl-propionic acid methyl ester 6f
D
disc)/cmꢀ1 2924 (s, CH), 1611 (w, C@C), 1114 (s, C–O),
1
1047 (s, C–O); H NMR (400MHz;CDCl ) 7.59–7.54
3
(5H, m, Ph), 7.37–7.16 (10H, m, Ph), 4.65–4.64 (1H,
m, C(6)H), 4.12–4.09 (1H, m, C(2)H), 3.70 (1H, dd,
0
0
0
J2,7 5.0 J7,7 10.0, C(7)H), 3.58 (1H, dd, J2,7 5.0 J7,7
10.0, C(70)H), 3.53 (2H, s, PhCH2N), 3.38 (3H, s,
By following the general procedure above, sodium cya-
noborohydride (1.6g, 1.7mmol) was added to a stirred
solution of L-phenylalanine methyl ester (73mg,
0.34mmol), the dialdehydes (0.44g, 1.02mmol) and
0
OCH3), 2.89–2.83 (2H, m, C(3,5)H), 2.20 (1H, dd, J5,5
0
11.0 J5 ,6 3.0, C(50)H), 1.93 (1H, app. t, J2,3 J3,3 11.0,
0
0
C(30)H), 1.02 (9H, s, C(CH3)3); 13C NMR (101
MHz;CDCl ) 136.7 (ArC), 135.8 (ArC), 134.3 (ArC),
˚
10A molecular sieves in methanol (40mL). Work-up
3
129.7 (ArC), 129.1 (ArC), 128.7 (ArC), 128.2 (ArC),
127.9 (ArC), 127.7 (ArC), 127.2 (ArC), 97.2 (C6), 69.1
(C2), 65.2 (C7), 63.4 (PhCH2N), 55.7 (C5), 55.0 (C3),
54.8 (OCH3), 26.8 (C(CH3)3), 19.2 (C(CH3)3); m/z (CI)
476 (65%, [M+H]+), 446 (42%, [MꢀOCH3]+), 220
and purification of the residue by flash column chroma-
tography (8:2 Et2O–hexane) afforded morpholine 5f
(2mg, 0.0036mmol, 1%) and [1,4]-oxazepane 6f (39mg,
0.068mmol, 20%) as clear oils.
(41%,
[MꢀOSi(Ph2)C(CH3)3]+),
found
[M+H]+
20
476.2633, C29H38NO3Si requires 476.2621.
Compound 5f: ½a ¼ þ18:8 (c 0.4, CHCl3); mmax (NaCl
D
disc)/cmꢀ1 2926 (s, CH), 2854 (s, CH), 1732 (s, C@O),
1113 (s, C–O), 1058 (s, C–O); 1H NMR (400MHz;
CDCl3) 7.74–7.18 (15H, m, Ph), 4.71–4.70 (1H, m,
C(6)H), 4.17–4.11 (1H, m, C(2)H), 3.70 (1H, dd,
20
Compound 6e: ½a ¼ þ71:0 (c 1.0, CHCl3); mmax (NaCl
D
disc)/cmꢀ1 3325 (br s, OH), 2930 (s, CH), 1173 (s, C–O),
1063 (s, C–O); H NMR (250MHz;CDCl ) 7.53–7.17
1
0
0
0
J2,7 5.0 J7,7 11.0, C(7)H), 3.59 (1H, dd, J2,7 5.0 J7,7
3
11.0, C(70)H), 3.54 (3H, s, OCH3), 3.49 (1H, dd, J 3.0
J 11.0, PhCH2CH), 3.41 (3H, s, OCH3), 3.11 (2H, m,
(15H, m, Ph), 4.37 (1H, d, J6,7 4.0, C(7)H), 4.15–4.05
(1H, m, C(2)H), 3.88 (1H, app. dd, J6,7 4.0 J5,6 7.0,
C(6)H), 3.69 (1H, d, J 13.0, PhCH2N), 3.60 (1H, d, J
0
PhCH2CH), 2.99 (1H, dd, J2,3 18.0 J3,3 12.0, C(3)H),
0
0
2.95 (1H, app. d, J5,5 11.0, C(5)H), 2.61 (1H, dd, J2,3
0
0
13.0, PhCH2N), 4.52 (1H, dd, J2,8 5.0 J8,8 10.0,
0
2.5 J3,3 12.0, C(30)H), 2.29 (1H, app. t, J5 ,6 J5,5 11.0,
C(8)H), 3.31 (1H, dd, J2,8 7.0 J8,8 10.0, C(80)H), 3.29
0
0
0
C(50)H), 1.06 (9H, s, C(CH3)3); 13C NMR (101
MHz;CDCl ) 171.2 (CO), 137.6 (ArC), 136.6 (ArC),
0
(3H, s, OCH3), 3.01 (1H, dd, J2,3 5.0 J3,3 12.0,
0
C(3)H), 2.96 (1H, dd, J5,6 7.0 J5,5 12.0, C(5)H), 2.62
0
3
(1H, app. d, J5,5 12.0, C(50)H), 2.12 (1H, dd, J2,3 10.0
136.2 (ArC), 129.8 (ArC), 129.2 (ArC), 128.8 (ArC),
128.2 (ArC), 127.8 (ArC), 127.1 (ArC), 126.6
(ArC), 97.1 (C6), 69.8 (PhCH2CH), 69.3 (C2), 65.1
(C7), 55.1 (OCH3), 54.2 (C5), 51.0 (OCH3), 50.3 (C3),
36.0 (PhCH2CH), 26.8 (C(CH3)3), 19.2 (C(CH3)3); m/z
(EI) 547 (13%, [M]+), 488 (82%, [MꢀCO2CH3]+),
456 (100%, [MꢀPhCH2]+), found [M]+ 547.2742,
C32H41NO5Si requires 547.2754.
0
J3,3 12.0, C(30)H), 0.87 (9H, s, C(CH3)3); 13C NMR
0
(63MHz;CDCl 3) 138.2 (ArC), 137.7 (ArC), 135.9
(ArC), 130.1 (ArC), 129.7 (ArC), 128.9 (ArC), 128.2
(ArC), 128.0 (ArC), 127.9 (ArC), 102.3 (C7), 72.2
(C2), 69.6 (C6), 65.7 (C8), 63.8 (PhCH2N), 58.9 (C3),
55.5 (OCH3), 53.8 (C5), 27.1 (C(CH3)3), 19.5
(C(CH3)3); m/z (CI) 506 (10%, [M+H]+), 218 (12%,
[MꢀOCH3–OSi(Ph2)C(CH3)3]+), 120 (37%, [PhCH2N-
CH2]+), found [M+H]+ 506.2713, C30H40NO4Si
requires 506.2727.
20
Compound 6f: ½a ¼ þ1:7 (c 1.9, CHCl3); mmax (NaCl
D
disc)/cmꢀ1 3382 (br s, OH), 2930 (s, CH), 1736 (s,
C@O), 1113 (s, C–O), 1069 (s, C–O); 1H NMR
(400MHz;CDCl 3) 7.60–7.54 (5H, m, Ph), 7.36–7.15
(10H, m, Ph), 4.43 (1H, d, J6,7 6.0, C(7)H), 4.12–4.05
(1H, m, C(2)H), 3.95–3.88 (1H, m, C(6)H), 3.68 (3H,
s, OCH3), 3.61 (1H, dd, J 10.0 J 5.0, PhCH2CH), 3.49
20
Compound 7e: ½a ¼ þ79:0 (c 1.0, CHCl3); mmax (NaCl
D
disc)/cmꢀ1 3357 (br s, OH), 2915 (s, CH), 1113 (s, C–O),
1040 (s, C–O); H NMR (250MHz;CDCl ) 7.76–7.28
1
3
0
(15H, m, Ph), 4.62 (1H, dd, J2,3 9.0 J2,3 5.0, C(2)H),
0
0
(1H, dd, J2,8 6.0 J8,8 10.0 C(8)H), 3.39 (1H, dd, J2,8
0
4.02–3.97 (1H, m, C(7)H), 3.91–3.89 (3H, m,
C(6,8,80)H), 3.84 (1H, d, J 13.5, PhCH2N), 3.74 (1H,
d, J 13.5, PhCH2N), 3.22 (3H, s, OCH3), 3.19 (1H,
6.0 J8,8 10.0 C(80)H), 3.35 (3H, s, OCH3), 3.16 (1H,
0
dd, J 14.0 J 5.0, PhCH2H), 3.13 (1H, dd, J5,6 7.0 J5,5
0
12.5 C(5)H), 2.99 (1H, app. d, J3,3 12.0 C(3)H), 2.90
0
0
0
app. d, J5,5 5.0, C(5)H), 2.94 (1H, dd, J3,3 14.5 J2,3
5.0, C(30)H), 2.59 (1H, dd, J3,3 ) 14.5 (J2,3 9.0, C(3)H),
2.56–2.54 (1H, m, C(50)H), 1.10 (9H, s, C(CH3)3); 13C
NMR (63MHz;CDCl 3) 139.1 (ArC), 136.0 (ArC),
135.4 (ArC), 129.90 (ArC), 128.7 (ArC), 128.5 (ArC),
127.9 (ArC), 127.6 (ArC), 100.7 (C2), 72.6 (C6), 71.7
(C7), 67.3 (C8), 63.1 (C5), 61.8 (PhCH2N), 58.8 (C3),
55.8 (OCH3), 27.2 (C(CH3)3), 19.6 (C(CH3)3); m/z (CI)
506 (16%, [M+H]+), 274 (14%, [MꢀOSi(Ph2)-
C(CH3)2]+), 218 (43%, [MꢀOCH3–OSi(Ph2)C(CH3)3]+),
found [M+H]+ 506.2727, C30H40NO4Si requires
506.2727.
(1H, dd, J 14.0 J 10.0, PhCH2CH), 2.76–2.69 (2H, m,
C(50,30)H), 1.03 (9H, s, C(CH3)3); 13C NMR (63MHz;
CDCl3) 172.7 (CO), 137.9 (ArC), 136.8 (ArC), 135.0
(ArC), 129.9 (ArC), 129.3 (ArC), 128.7 (ArC), 128.2
(ArC), 127.9 (ArC), 127.6 (ArC), 127.1 (ArC), 102.1
(C7), 72.5 (C2), 69.9 (PhCH2CH), 69.5 (C6), 65.6 (C8),
58.6 (C3), 56.3 (OCH3), 52.0 (OCH3), 51.0 (C5), 36.3
(PhCH2CH), 27.2 (C(CH3)3), 19.6 (C(CH3)3); m/z (CI)
578 (63%, [M+H]+), 486 (82%, [MꢀPhCH2]+), 454
(10%, [MꢀOCH3–PhCH2]+), found [M+H]+ 578.2939,
C33H44NO6Si requires 578.2938.
0