Norstatines by Organocatalytic α-Amination and Passerini Reaction
NMR (CDCl3, 300 MHz): δ = 8.00 (br. s, 1 H), 6.78 (br. s, 1 H),
FULL PAPER
1 H), 2.31 (t, J = 7.0 Hz, 2 H), 1.40 (s, 9 H), 1.39 (s, 9 H), 1.01
(d, 3J = 6.8 Hz, 6 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 172.4,
156.4, 79.5, 79.4, 66.8, 61.3, 60.3, 53.6, 51.2, 28.5, 21.6, 17.6 ppm.
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4.85 (d, J = 6.3 Hz, 1 H), 4.59–4.30 (m, 2 H), 4.05–3.93 (m, 1 H),
3.71–3.56 (m, 1 H), 1.90–1.64 (m, 4 H), 1.60–1.56 (m, 6 H), 1.27
(d, 3J = 6.3 Hz, 15 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = MS (EI): m/z = 475 (M+).
172.7, 156.6, 66.9, 66.5, 51.4, 47.7, 33.8, 28.2, 23.6, 22.5, 12.0 ppm.
Diisopropyl 1-[(1R,2R)-3-(Cyclohexylamino)-2-hydroxy-3-oxo-1-(2-
propyl)propyl]hydrazine-1,2-dicarboxylate (48a): Yield 0.116 g
MS (EI): m/z = 387 (M+).
(R)-Diisopropyl
1-[2-Hydroxy-1-methyl-3-(2-morpholinoethyl- (40%). 1H NMR (CDCl3, 300 MHz): δ = 7.40 (br. s, 1 H), 6.36 (br.
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amino)-3-oxopropyl]hydrazine-1,2-dicarboxylate (39a): Yield 0.167 g
s, 1 H), 4.98–4.80 (m, 2 H), 4.35 (d, J = 6.3 Hz, 1 H), 4.19–4.10
(80%). 1H NMR (CDCl3, 300 MHz): δ = 7.26 (br. s, 1 H), 6.55 (br. (m, 1 H), 3.75–3.60 (m, 1 H), 2.32–2.22 (m, 1 H), 1.85–1.75 (m, 4
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s, 1 H), 4.78 (d, J = 6.8 Hz, 1 H), 4.15–4.07 (m, 1 H), 3.63 (t, J
H), 1.68–1.56 (m, 6 H), 1.24 (d, J = 6.3 Hz, 12 H), 0.89 (d, J =
= 7.0 Hz, 2 H), 3.34 (t, J = 7.0 Hz, 2 H), 2.42 (t, 3J = 7.0 Hz, 2 6.3 Hz, 6 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 170.9, 156.5,
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H), 2.33 (t, J = 7.0 Hz, 2 H), 1.35 (d, J = 6.8 Hz, 6 H) ppm. 13C 65.7, 64.4, 48.2, 48.0, 32.8, 27.6, 25.6, 24.9, 22.0, 19.3 ppm. MS
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NMR (CDCl3, 75 MHz): δ = 171.8, 156.6, 156.1, 71.2, 71.0, 66.9,
(EI): m/z = 415 (M+).
54.3, 51.2, 37.8, 23.7, 8.9 ppm. MS (EI): m/z = 418 (M+).
Diisopropyl 1-[(1R,2S)-3-(Cyclohexylamino)-2-hydroxy-3-oxo-1-(2-
(R)-Di-tert-butyl 1-[3-(Cyclohexylamino)-1-ethyl-2-hydroxy-3-oxo- propyl)propyl]hydrazine-1,2-dicarboxylate (48b): Yield 0.174 g
propyl]hydrazine-1,2-dicarboxylate (41a): Yield 0.274 g (80%). 1H
NMR (CDCl3, 300 MHz): δ = 7.99 (br. s, 1 H), 6.20 (br. s, 1 H),
4.78 (d, J = 6.3 Hz, 1 H), 4.15–4.00 (m, 1 H), 3.72–3.60 (m, 1 H),
1.70–1.53 (m, 4 H), 1.55–1.52 (m, 2 H), 1.46–1.43 (m, 6 H), 1.40
(s, 18 H), 0.96 (t, 3J = 6.3 Hz, 3 H) ppm. 13C NMR (CDCl3,
75 MHz): δ = 171.9, 156.6, 79.5, 63.0, 56.7, 47.6, 33.8, 33.6, 28.2,
28.1, 23.6, 22.9, 15.7, 9.9 ppm. MS (EI): m/z = 429 (M+).
(60%). 1H NMR (CDCl3, 300 MHz): δ = 7.20 (br. s, 1 H), 6.67 (br.
s, 1 H), 4.95–4.75 (m, 2 H), 4.25 (d, J = 6.3 Hz, 1 H), 3.78–3.61
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(m, 2 H), 2.40–2.29 (m, 1 H), 1.88–1.72 (m, 4 H), 1.68–1.52 (m, 6
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H), 1.15 (d, 3J = 6.3 Hz, 12 H), 0.98 (d, J = 6.3 Hz, 6 H) ppm.
13C NMR (CDCl3, 75 MHz): δ = 170.9, 156.5, 65.7, 64.4, 48.2,
48.0, 33.3, 27.4, 25.6, 24.9, 22.0, 17.9 ppm. MS (EI): m/z = 415
(M+).
(R)-Di-tert-butyl 1-[1-Ethyl-2-hydroxy-3-(2-morpholinoethylamino)-
3-oxopropyl]hydrazine-1,2-dicarboxylate (42a): Yield 0.356 g (80%).
(R)-Diisopropyl 1-[2-Hydroxy-3-(2-morpholinoethylamino)-3-oxo-1-
(2-propyl)propyl]hydrazine-1,2-dicarboxylate (49a): Yield 0.192 g
(60%). H NMR (CDCl3, 300 MHz): δ = 8.11 (br. s, 1 H), 4.95–
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1H NMR (CDCl3, 300 MHz): δ = 8.07 (br. s, 1 H), 4.75 (d, J =
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6.7 Hz, 1 H), 4.10–4.07 (m, 1 H), 3.67 (t, J = 7.0 Hz, 2 H), 3.33
4.70 (m, 3 H), 3.77–3.58 (m, 5 H), 3.40 (d, 3J = 7.0 Hz, 2 H), 2.68–
2.55 (m, 2 H), 2.50–2.37 (m, 5 H), 1.30–1.10 (m, 12 H), 0.90–0.77
(m, 6 H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 172.4, 156.4, 66.9,
66.8, 61.3, 60.3, 53.6, 51.2, 37.9, 23.5, 23.4, 21.6, 17.6 ppm. MS
(EI): m/z = 446 (M+).
(t, 3J = 7.0 Hz, 2 H), 2.59 (t, 3J = 7.0 Hz, 2 H), 2.31 (t, 3J = 7.0 Hz,
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2 H), 1.55–1.51 (m, 2 H), 1.40 (s, 18 H), 0.96 (t, J = 6.8 Hz, 2 H)
ppm. 13C NMR (CDCl3, 75 MHz): δ = 172.4, 156.4, 79.5, 79.4,
66.8, 53.7, 51.2, 28.5, 14.9, 8.9 ppm. MS (EI): m/z = 461 (M+).
(R)-Diisopropyl 1-[1-Ethyl-2-hydroxy-3-(2-morpholinoethylamino)- (R)-Di-tert-butyl 1-[3-(Cyclohexylamino)-2-hydroxy-3-oxo-1-phenyl-
3-oxopropyl]hydrazine-1,2-dicarboxylate (43a): Yield 0.189 g (60%).
1H NMR (CDCl3, 300 MHz): δ = 7.58 (br. s, 1 H), 7.43 (br. s, 1
H), 4.92 (d, 3J = 6.7 Hz, 1 H), 4.08–4.01 (m, 1 H), 3.65 (t, 3J =
propyl]hydrazine-1,2-dicarboxylate (51a): Yield 0.373 g (80%). 1H
NMR ([D6]DMSO, 300 MHz): δ = 8.60 (br. s, 1 H), 7.66 (br. s, 1
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H), 7.59–7.43 (m, 5 H), 5.17 (d, J = 6.3 Hz, 2 H) 3.54–3.40 (m, 1
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7.0 Hz, 2 H), 3.32 (t, J = 7.0 Hz, 2 H), 2.45 (t, J = 7.0 Hz, 2 H),
H), 1.93–1.45 (m, 10 H), 1.40 (s, 9 H), 1.26 (s, 9 H) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 170.3, 156.6, 141.6, 129.5, 128.5, 128.4,
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2.31 (t, J = 7.0 Hz, 2 H), 1.88–1.86 (m, 2 H), 1.20 (d, 3J = 6.8 Hz,
12 H), 0.89 (t, 3J = 6.8 Hz, 2 H) ppm. 13C NMR (CDCl3, 75 MHz): 128.2, 127.0, 82.5, 77.6, 77.1, 48.6, 47.6, 32.8, 32.6, 28.2, 25.7, 24.9,
δ = 172.3, 156.3, 77.5, 77.4, 66.6, 65.9, 57.1, 53.4, 51.2, 35.6, 21.9,
24.7 ppm. MS (EI): m/z = 478 (M+).
21.0, 14.2, 8.9 ppm. MS (EI): m/z = 432 (M+).
(R)-Di-tert-butyl 1-[2-Hydroxy-3-(2-morpholinoethylamino)-3-oxo-
(R)-Diisopropyl
1-[3-(Cyclohexylamino)-1-ethyl-2-hydroxy-3-oxo- 1-phenylpropyl]hydrazine-1,2-dicarboxylate (52a): Yield 0.292 g
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propyl]hydrazine-1,2-dicarboxylate (44a): Yield 0.234 g (80%). 1H
NMR (CDCl3, 300 MHz): δ = 8.01 (br. s, 1 H), 6.80 (br. s, 1 H),
(80%). H NMR (CDCl3, 300 MHz): δ = 8.05 (br. s, 1 H), 7.45–
7.12 (m, 5 H), 5.17 (d, 3J = 7.0 Hz, 2 H), 3.65–3.50 (m, 4 H), 3.33–
3.28 (m, 2 H), 2.60–2.44 (m, 2 H), 2.40–2.30 (m, 4 H), 1.40 (s, 18
H) ppm. 13C NMR (CDCl3, 75 MHz): δ = 172.4, 156.4, 143.5,
128.5, 128.4, 127.0, 126.8, 80.4, 79.5, 79.4, 66.8, 57.7, 53.6, 51.2,
37.7, 28.5 ppm. MS (EI): m/z = 508 (M+).
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4.90 (d, J = 6.3 Hz, 1 H), 4.15–4.00 (m, 2 H), 3.72–3.60 (m, 1 H),
3.54–3.50 (m, 1 H), 1.70–1.53 (m, 4 H), 1.55–1.52 (m, 2 H), 1.50–
1.43 (m, 6 H), 1.35 (d, 3J = 6.3 Hz, 12 H), 1.0 (t, 3J = 6.3 Hz, 3 H)
ppm. 13C NMR (CDCl3, 75 MHz): δ = 171.8, 156.6, 70.1, 66.9,
63.0, 56.7, 47.6, 32.8, 32.6, 28.2, 23.6, 22.9, 14.2, 10.9 ppm. MS
(EI): m/z = 401 (M+).
(R)-Di-tert-butyl 1-[1-Benzyl-3-(cyclohexylamino)-2-hydroxy-3-oxo-
propyl]hydrazine-1,2-dicarboxylate (56a): Yield 0.239 g (80%). 1H
(R)-Di-tert-butyl 1-[3-(Cyclohexylamino)-2-hydroxy-3-oxo-1-(2-pro- NMR (CDCl3, 300 MHz): δ = 7.99 (br. s, 1 H), 7.23–7.12 (m, 5
pyl)propyl]hydrazine-1,2-dicarboxylate (46a): Yield 0.286 g (80%).
H), 5.90 (br. s, 1 H), 4.60–4.45 (m, 1 H), 4.05 (d, 3J = 6.3 Hz, 1
H), 3.75–3.65 (m, 1 H), 3.15–3.00 (m, 1 H), 2.87–2.79 (m, 1 H),
1.90–1.45 (m, 10 H), 1.40 (s, 9 H), 1.26 (s, 9 H) ppm. 13C NMR
1H NMR (CDCl3, 300 MHz): δ = 7.39 (br. s, 1 H), 6.21 (br. s, 1
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H), 4.31 (d, J = 6.3 Hz, 1 H), 4.20–4.14 (m, 2 H), 3.68–3.63 (m, 1
H), 2.45–2.32 (m, 1 H), 1.85–1.75 (m, 4 H), 1.68–1.56 (m, 6 H), (CDCl3, 75 MHz): δ = 170.4, 155.6, 138.5, 128.9, 128.7, 126.7, 83.0,
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1.40 (s, 18 H), 0.89 (d, J = 6.3 Hz, 6 H) ppm. 13C NMR (CDCl3, 82.6, 71.4, 62.7, 56.6, 48.6, 33.2, 32.8, 32.6, 28.2, 28.0, 25.6, 24.9,
75 MHz): δ = 171.9, 156.1, 79.1, 61.5, 60.5, 47.7, 33.7, 22.9, 28.0,
24.6 ppm. MS (EI): m/z = 491 (M+).
27.9, 21.6, 17.3 ppm. MS (EI): m/z = 443 (M+).
(S)-Di-tert-butyl 1-[3-(Benzylamino)-2-hydroxy-1-methyl-3-oxoprop-
(R)-Di-tert-butyl 1-[2-Hydroxy-3-(2-morpholinoethylamino)-3-oxo- yl]hydrazine-1,2-dicarboxylate (59a): Yield 0.182 g (50%). 1H NMR
1-(2-propyl)propyl]hydrazine-1,2-dicarboxylate (47a): Yield 0.259 g
(CDCl3, 300 MHz): δ = 7.67 (br. s, 1 H), 7.27–7.18 (m, 5 H), 6.39
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(70%). 1H NMR (CDCl3, 300 MHz): δ = 7.91 (br. s, 1 H), 4.75 (d,
(br. s, 1 H), 4.75 (d, J = 6.8 Hz, 1 H), 4.45 (s, 2 H), 4.30–4.20 (m,
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3J = 6.7 Hz, 1 H), 4.90–4.05 (m, 1 H), 3.66 (t, J = 7.0 Hz, 2 H),
1 H), 1.40 (s, 18 H), 1.25 (d, 3J = 6.8 Hz, 3 H) ppm. 13C NMR
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3.33 (t, J = 7.0 Hz, 2 H), 2.59 (t, J = 7.0 Hz, 2 H), 2.45–2.42 (m, (CDCl3, 75 MHz): δ = 171.4, 156.6, 141.6, 128.7, 128.6, 127.8,
Eur. J. Org. Chem. 2006, 4585–4595
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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