Chiral Polyamino Alcohols via Hydroaminomethylation
FULL PAPERS
56.5, 60.4, 67.1, 69.8, 127.0, 129.2, 138.0, 158.7; IR (film,
1.08 mmol) and (S)-4-benzyl-3-(2-methylallyl)oxazolidin-2-
one 1a (500 mg, 2.16 mmol). The crude product was purified
by flash chromatography on alumina activity III to get chiral
polyamine 6a as an oil; yield: 519 mg (84%). 1H NMR
(400 MHz, CDCl3): d=0.86–0.90 (6H, m), 1.24 and 1.52
(4H, m), 1.84 (2H, m), 2.52–2.63 (8H, m), 2.88–2.90 (2H,
m), 3.31–3.36 (2H, m), 3.05–3.08 (4H, m), 3.97 (4H, m),
˜
KBr): n=701, 759, 867, 1118, 1454, 1625, 1751, 2809, 2854,
2954, 3390 cmÀ1; ESI-MS: m/z=319.1 [M+H]+; HR-MS
(FAB): m/z=319.1860, calcd. for C18H26N2O3 [M+H]+:
319.1943.
(S)-4-Isopropyl-3-(2-methyl-4-morpholinobutyl)oxazoli-
din-2-one (3c): The general procedure A for hydroaminome-
thylation was followed with (S)-4-isopropyl-3-(2-methyl-
4.13
CDCl3): d=17.7, 30.1, 38.3, 47.8, 48.3, 52.8, 53.2, 56.0, 56.5,
(2H, m), 7.14–7.25 (10H, m); 13C NMR (400 MHz,
ACHTUNGTRENNUNG
ACHTUNGTRENNUNGallyl)oxazolidin-2-one 1c (213 mg, 1.163 mmol) and morpho-
˜
line (104 mg, 1.163 mmol). The crude product was purified
by flash chromatography on alumina activity III to give
chiral amine 3c as an oil; yield: 265 mg (79%, 0.91 mmol).
1H NMR (400 MHz, CDCl3): d=0.79–1.01 (9H, m), 1.14–
1.43 (2H, m), 1.69–1.94 (H, m), 2.02–2.16 (1H, m), 2.29–2.55
(4H, m), 2.78–2.94 (1H, m), 3.31–3.34 (1H, m), 3.62–3.77
(4H, m), 4.07–4.24 (3H, m); 13C NMR (100 MHz, CDCl3):
d=17.5, 18.1, 27.3, 29.5, 30.6, 53.8, 56.7, 58.3, 62.6, 67.1,
66.8, 128.6, 130.3, 130.5, 137.0, 159.7; IR (film, KBr): n=702,
743, 762, 1006, 1059, 1175, 1259, 1380, 1454, 1496, 1603,
1747, 2810, 2926, 3026, 3500 cmÀ1; LR-MS (FAB): m/z=
577.7 [M+H]+; HR-MS (FAB): m/z=576.3734, calcd. for
C34H48N4O4 [M+H]+: 576.3676.
Chiral polyamine (6b): The general procedure A for hy-
droaminomethylation was followed with piperazine (158 mg,
1.84 mmol) and (S)-4-phenyloxazolidin-2-one 1b (800 mg,
3:68 mmol). The crude product was purified by flash chro-
matography on alumina activity III to get chiral polyamine
6b as an oil; yield: 898 mg (91%). 1H NMR (400 MHz,
CDCl3): d=0.80–0.96 (6H, m), 1.21–1.34 (2H, m), 1.64–1.78
(2H, m), 1.36–1.34 (1H, m), 1.50–1.63 (2H, m), 2.13–2.56
(8H, m), 2.56–2.77 (2H, m), 3.20–3.37 (4H, m), 4.11–4.22
(2H, m), 4.59–4.71 (2H, m), 4.73–4.86 (2H, m), 7.25–7.48
(10H, m); 13C NMR (100 MHz, CDCl3): d=17.3, 29.8, 36.0,
47.8, 52.9, 56.1, 59.7, 69.7, 127.0,129.0, 129.2, 137.8; IR (film,
˜
68.6, 159. 8. IR (film, KBr): n=867, 914, 1118, 1286, 1373,
1461, 1621, 1741, 2884, 2956 cmÀ1; ESI-MS: m/z=285.3
[M+H]+ HR-MS (FAB): m/z=285.2025, calcd. for
C15H25N3O2 [M+H]+: 285.21.
(S)-2-(2-Methyl-4-morpholinobutylamino)-3-phenylpro-
pan-1-ol (4a): The general procedure B for hydrolysis was
followed with 3a (300 mg, 0.902 mmol), to get chiral amino
alcohol 4a as an oil; yield: 224 mg (81%). 1H NMR
(400 MHz, CDCl3): d=0.84–0.99 (3H, m), 1.29–1.41 (2H,
˜
m), 1.84–1.87 (1H, m), 2.21–2.31
G
KBr): n=701, 761, 873, 1060, 1120, 1230, 1253, 1417, 1457,
m), 2.79–2.95 (1H, m), 3.21–3.32 (1H, m), 2.99–3.09 (2H,
m), 3.63–3.78 (4H, m), 3.82 (1H, m), 4.31–4.45 (2H, m),
7.11–7.27 (5H, m); 13C NMR (400 MHz, CDCl3): d=18.1,
30.1, 38.3, 50.8, 51.8, 53.5, 56.0, 57.5, 66.8, 128.6, 129.3, 131.5,
1751, 2809, 2925, 2952, 3488 cmÀ1; LR-MS (FAB): m/z=
549.0 [M+H]+; HR-MS (FAB): m/z=548.3390, calcd. for
C32H44N4O4 [M+H]+: 548.3363.
Chiral polyamine (6c): The general procedure A for hy-
droaminomethylation was followed with piperazine (117 mg,
1.36 mmol) and (S)-4-isopropyl-3-(2-methylallyl)oxazolidin-
2-one 1c (500 mg, 2.72 mmol). The crude product was puri-
fied by flash chromatography on alumina activity III to get
chiral polyamine 6c as an oil without any further purifica-
˜
137.0; IR (film, KBr): n=698, 743, 771, 1001, 1044, 1139,
1251, 1389, 1459, 1505, 1611, 2810, 2933, 3042, 3521 cmÀ1
LR-MS (FAB): m/z=307.2 [M+H]+; HR-MS (FAB): m/z=
307.2358, calcd. for C18H30N2O2 [M+H]+: 307.2307.
(S)-2-(2-Methyl-4-morpholinobutylamino)-2-phenyletha-
nol (4b): The general procedure B for hydrolysis was fol-
lowed with (S)-3-(2-methyl-4-morpholinobutyl)-4-phenylox-
azolidin-2-one (700 mg, 2.19 mmol) 3b to get chiral amino
alcohol 4b as an oil; yield: 603 mg (93%, 2.03 mmol).
1H NMR (400 MHz, CDCl3): d=0.90–0.95 (3H, m), 1.26–
1.30 (2H, m), 1.66–1.74 (1H, m), 2.35–2.51 (8H, m), 3.71–
3.75 (6H, m), 7.21–7.39 (5H, m); 13C NMR (100 MHz,
CDCl3): d=18.5, 31.1, 36.6, 53.7, 57.0, 62.1, 66.6, 68.9. 69.7,
1
tion; yield: 590 mg (90%). H NMR (400 MHz, CDCl3): d=
0.79–0.98 (18H, m), 1.20–1.32 (1H, m), 1.34–1.44 (2H, m),
1.46–1.62 (4H, m), 1.74–1.89 and 2.00–2.15 (4H, m), 2.26–
2.61 (8H, m), 2.74–2.94 and 3.26–3.41 (4H, m), 3.71–3.74
(2H, m), 4.05–4.24 (4H, m); 13C NMR (100 MHz, CDCl3):
d=14.0, 17.6, 27.1, 29.7, 31.3, 47.2, 58.6, 59.2, 62.4, 68.3,
˜
158.4; IR (film, KBr): n=769, 873, 1051, 1120, 1253, 1425,
1758, 2807, 2929, 2958, 3311 cmÀ1; HR-MS (ESI-FT-MS):
m/z=481.3735, calcd. for C26H48N4O4 [M+H]+: 481.3676.
Chiral polyamino alcohol (7a):The general procedure B
for hydrolysis was followed with polyamine 6a (350 mg,
0.61 mmol), to get chiral polyamino alcohol 7a as an oil;
127.5, 129.7, 137.0; IR (film, KBr): n=701, 759, 867, 1118,
1454, 1625, 2809, 2854, 2954, 3390 cmÀ1; ESI-MS: m/z=
293.2 [M+H]+; HR-MS (FAB): m/z=292.2226, calcd. for
C17H28N2O2 [M+H]+: 292.2151.
1
(S)-2-(2-Methyl-4-morpholinobutylamino)-3-methylbutan-
1-ol (4c): The general procedure B for hydrolysis was fol-
lowed with (S)-4-isopropyl-3-(2-methyl-4-morpholinobutyl)-
oxazolidin-2-one 3c (200 mg, 0.703 mmol) to get chiral
amino alcohol 4c as an oil; yield: 163 mg (89%, 0.62 mmol).
1H NMR: (400 MHz, CDCl3): d=0.87–1.01 (9H, m), 1.21–
1.41 (2H, m), 1.56–1.73 (1H, m), 2.25.2.76 (8H, m),3.67–
3.78 (6H, m); 13C NMR: (100 MHz, CDCl3): d=18.7, 20.0,
29.2, 31.9, 33.0, 53.8, 54.2, 57.4, 60.7, 62.1, 67.3; IR: (film,
yield: 259 mg (80%). H NMR (400 MHz, CDCl3): d=0.88–
1.02 (6H, m), 1.31–1.49 (4H, m), 1.84 (2H, m), 2.52–2.63
(8H, m), 2.88–2.90 (2H, m), 3.31–3.36 (2H, m), 3.11–3.19
(4H, m), 3.86–4.01 (4H, m), 4.31ACTHUNTGRNEUNG(2H, m), 7.14–7.25 (10H,
m); 13C NMR (400 MHz, CDCl3): d=17.7, 29.1, 39.8, 50.0,
51.2, 52.6, 55.2, 56.0, 57.3, 69.1, 128.6, 130.3, 130.5, 135.0; IR
˜
(film, KBr): n=705, 743, 762, 1011, 1059, 1175, 1259, 1380,
1454, 1496, 1603, 2810, 2956, 3026, 3506 cmÀ1; LR-MS
(FAB): m/z=525.4 [M+H]+; HR-MS (FAB): m/z=525.415,
calcd. for C32H52N4O2 [M+H]+: 525.409.
˜
KBr): n=867, 914, 1118, 1286, 1373, 1461, 1621, 2884, 2956,
3380 cmÀ1; ESI-MS: m/z=259.3 [M+H]+; HR-MS (FAB):
m/z=258.2218, calcd. for C14H30N2O2 [M+H]+: 258.2307.
Chiral polyamine (6a): The general procedure A for hy-
droaminomethylation was followed with piperazine (93 mg,
2-(4-{4-[4-(2-Hydroxy-1-phenylethylamino)-3-methylbu-
tyl]-piperazin-1-yl}-2-methylbutylamino)-2-phenylethanol
(7b): The general procedure B for hydrolysis was followed
with polyamine 6b (347 mg, 0.265 mmol), to get chiral polya-
Adv. Synth. Catal. 2009, 351, 2113 – 2123
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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