T. Kiguchi et al. / Tetrahedron 56 (2000) 5819±5833
5831
cis-4-(Methoxyamino)-3-methyl-1-[(4-methylphenyl)sul-
fonyl]pyrrolidin-3-ol (20a). 14% Yield in two steps from
18a; a colorless oil; IR 3700±3350 (OH, NH), 1346, 1160
(NSOO) cm21;1H NMR (300 MHz) d 7.71 (2H, br d,
J8 Hz, ArH), 7.33 (2H, br d, J8 Hz, ArH), 5.50 (1H,
br s, NH), 3.59 (1H, dd, J10, 7.5 Hz, 5-H), 3.40 (3H, s,
OMe), 3.36±3.20 (3H, m, 2-H2, 4-H), 3.04 (1H, dd, J10,
8 Hz, 5-H), 2.43 (3H, s, ArMe), 1.31 (3H, s, Me); HRMS
(EI, m/z) calcd for C13H20N2O4S (M1) 300.1143, found
300.1169.
3-Methoxyamino-3-methyl-1-[(4-methylphenyl)sulfonyl]-
pyrrolidine (21). 53% yield from 18d; pale yellow crystals
from Et2O; mp 92±938C; IR 1343, 1160 (NSOO) cm21; 1H
NMR (300 MHz) d 7.72 (2H, br d, J8 Hz, ArH), 7.33 (2H,
br d, J8 Hz, ArH), 5.20 (1H, br s, NH), 3.40±3.20 (2H, m,
5-H2), 3.37 (3H, s, OMe), 3.32 and 2.94 (2H, ABq,
J10 Hz, 2-H2), 2.44 (3H, s, ArMe), 1.86 (1H, br ddd,
J12, 8, 5 Hz, 4-H), 1.63 (1H, dt, J13, 8 Hz, 4-H), 1.15
(3H, s, Me); HRMS (EI, m/z) calcd for C13H20N2O3S (M1)
284.1194, found 284.1175. Anal. Calcd for C13H20N2O3S:
C, 54.91; H, 7.09; N, 9.85. Found: C, 54.80; H, 7.37; N,
9.83.
trans-4-(Methoxyamino)-4-methyl-1-[(4-methylphenyl)-
sulfonyl]pyrrolidin-3-ol (19b). 29% Yield in two steps
from 17b; colorless crystals from AcOEt; mp 118±1208C;
[1R-(1a,2b,3a,4b,5a)]-1-Methoxyamino-2,3,4-tris(phenyl-
methoxy)-5-[(phenylmethoxy)methyl]cyclopentane (22).
1
IR 3630±3370 (OH, NH), 1346, 1161 (NSOO) cm21; H
1
46% Yield from 18e; a colorless oil; H NMR (500 MHz)
NMR (300 MHz) d 7.72 (2H, br d, J8 Hz, ArH), 7.33
(2H, br d, J8 Hz, ArH), 5.10 (1H, br s, NH), 4.08 (1H,
br t, J6 Hz, 3-H), 3.68 (1H, dd, J10.5, 6 Hz, 2-H), 3.39
(3H, s, OMe), 3.12 (1H, dd, J10.5, 5 Hz, 2-H), 3.27 and
3.09 (2H, ABq, J10 Hz, 5-H2), 2.44 (3H, s, ArMe), 1.98
(1H, br s, OH), 1.09 (3H, s, Me); HRMS (EI, m/z) calcd for
C13H20N2O4S (M1) 300.1142, found 300.1158. Anal. Calcd
for C13H20N2O4S: C, 51.98; H, 6.71; N, 9.33. Found: C,
51.97; H, 6.89; N, 9.29.
d 7.39±7.23 (20H, m, ArH), 5.97 (1H, br s, OH), 4.70±4.44
(8H, m, CH2Ph£4), 4.00 (1H, br t, J6 Hz, 3-H), 3.96 (1H,
br dd, J8, 5.5 Hz, 4-H), 3.86 (1H, br t, J5 Hz, 2-H),
3.66±3.60 (2H, m, 6-H2), 3.59 (1H, m, 1-H), 3.47(3H, s,
OMe), 2.54 (1H, br quint., J7 Hz, 5-H); HRMS (EI, m/z)
calcd for C35H39NO5 (M1) 553.2826, found 553.2816.
[1R-(1a,2b,3a,4b,5b)-1-Methoxyamino-2,3,4-tris(phenyl-
methoxy)-5-[(phenylmethoxy)methyl]cyclopentanamine
(23). 23% Yield from 18e; a colorless oil; 1H NMR
(500 MHz) d 7.36±7.23 (20H, m, ArH), 5.78 (1H, br s,
NH), 4.67±4.48 (8H, m, CH2Ph£4), 3.99±3.92 (3H, m,
2±4-H), 3.79 (1H, dd, J9.5, 7 Hz, 6-H), 3.68 (1H, dd,
J9.5, 7 Hz, 6-H), 3.48 (3H, s, OMe), 3.39 (1H, m, 5-H),
2.49 (1H, m, 1-H); HRMS (EI, m/z) calcd for C35H39NO5
(M1) 553.2826, found 553.2804.
cis-4-(Methoxyamino)-4-methyl-1-[(4-methylphenyl)sul-
fonyl]pyrrolidin-3-ol (20b). 7% Yield in two steps from
17b; a colorless oil; IR 3600±3340 (OH, NH), 1346, 1160
1
(NSOO) cm21; H NMR (200 MHz) d 7.71 (2H, br d,
J8 Hz, ArH), 7.32 (2H, br d, J8 Hz, ArH), 5.82 (1H,
br s, NH), 3.89 (1H, m, 3-H), 3.58 (1H, m, 2-H), 3.40
(3H, s, OMe), 3.26 (1H, br dd, J11, 3 Hz, 2-H), 3.19
and 3.07 (2H, ABq, J10 Hz, 5-H2), 2.43 (3H, s, ArMe),
1.11 (3H, br s, Me); HRMS (EI, m/z) calcd for C13H20N2O4S
(M1) 300.1142, found 300.1138.
General method for reaction of methoxyamines 19±23
with Red-Alw
trans-4-(Methoxyamino)-1-[(4-methylphenyl)sulfonyl]-
pyrrolidin-3-ol (19c). 23% yield in two steps from 17c;
colorless needless from AcOEt-Et2O; mp 111±1138C; IR
To solution of the methoxyamine 19±23 (0.17 mmol) in
benzene (2 ml) was added Red-Alw (70% in toluene)
(112 mg, 0.5 mmol) at room temperature. After being
re¯uxed for 1±2 h, 20% NaOH solution was added to the
reaction mixture and the mixture was diluted with AcOEt.
The precipitate was ®ltered through a pad of Celite and the
®ltrate was concentrated at reduced pressure. Puri®cation of
the residue by short column chromatography (CHCl3±
MeOH 9:1) afforded the corresponding demethoxylated
amines and/or the ring expansion product 25. Yields were
shown in Table 4. The spectral data of 25 were found to be
identical with those of the authentic sample.16
3680±3300 (NH, OH), 1345, 1160 (NSOO) cm21 1H
;
NMR (300 MHz) d 7.72 (2H, br d, J8.5 Hz, ArH), 7.34
(2H, br d, J8.5 Hz, ArH), 5.39 (1H, br s, NH), 4.18 (1H, m,
3-H), 3.66 (1H, dd, J10.5, 5 Hz, 2-H), 3.50 (1H, dd,
J10.5, 6.5 Hz, 5-H), 3.45 (1H, m, 4-H), 3.41 (3H, s,
OMe), 3.18 (1H, dd, J10.5, 3.5 Hz, 2-H), 3.13 (1H, dd,
J10.5, 4 Hz, 5-H), 2.44 (3H, s, ArMe), 2.07 (1H, br s,
OH); HRMS (EI, m/z) calcd for C12H18N2O4S (M1)
286.0986, found 286.098. Anal. Calcd for C12H18N2O4S:
C, 50.34; H, 6.34; N, 9.78. Found: C, 50.26; H, 6.30; N,
9.74.
trans-4-Amino-3-methyl-1-[(4-methylphenyl)sulfonyl]-
pyrrolidin-3-ol (24a). Colorless crystals from CHCl3±
Et2O; mp 144±1468C; IR 3650±3400 (OH, NH), 1347,
cis-4-(Methoxyamino)-1-[(4-methylphenyl)sulfonyl]pyrro-
lidin-3-ol (20c). 12% Yield in two steps from 17c; colorless
needless from Et2O; mp 89±908C; IR 3600±3350 (OH,
1
1160 (NSOO) cm21; H NMR (300 MHz) d 7.72 (2H, br
d, J8 Hz, ArH), 7.34 (2H, br d, J8 Hz, ArH), 3.64 (1H,
br dd, J10, 7 Hz, 5-H), 3.34 and 3.22 (2H, ABq, J10 Hz,
2-H2), 3.12 (1H, br t, J6 Hz, 4-H), 2.99 (1H, br dd, J10,
7 Hz, 5-H), 2.42 (3H, s, ArMe), 1.19 (3H, s, Me); HRMS
(EI, m/z) calcd for C12H18N2O3S (M1) 270.1037, found
270.1048. Anal. Calcd for C12H18N2O3S: C, 53.31; H,
6.71; N, 10.36. Found: C, 53.04; H, 6.55; N, 10.34.
1
NH), 1347, 1163 (NSOO) cm21; H NMR (300 MHz) d:
7.71 (2H, br d, J8 Hz, ArH), 7.33 (2H, br d, J8 Hz,
ArH), 5.77 (1H, br s, NH), 4.25 (1H, br s, 3-H), 3.60±
3.50 (2H, m, 4, 5-H), 3.49 (1H, dd, J11, 4.5 Hz, 2-H),
3.45 (3H, s, OMe), 3.35 (1H, br dd, J11, 2.5 Hz, 2-H),
2.96 (1H, m, 5-H), 2.58 (1H, br s, OH), 2.43 (3H, s, ArMe);
HRMS (EI, m/z) calcd for C12H18N2O4S (M1) 286.0986,
found 286.0995. Anal. Calcd for C12H18N2O4S: C, 50.34;
H, 6.34; N, 9.78. Found: C, 50.33; H, 6.30; N, 9.73.
trans-4-Amino-1-[(4-methylphenyl)sulfonyl]pyrrolidin-
3-ol (24b). Colorless crystals from CHCl3; mp 115±1168C;