C. Miniejew et al. / Tetrahedron 62 (2006) 2657–2670
2665
C21H27NO2: C, 77.50; H, 8.36; N, 4.30. Found: C, 77.72; H,
8.56; N, 4.61. [a]2D5 C4.9 (c 1.0 in CHCl3).
141.3, 143.2 (Ph), 172.6 (C-1). Anal. Calcd for C27H31NO2:
C, 80.76; H, 7.78; N, 3.49. Found: C, 81.02; H, 8.04; N,
3.76. [a]2D5 C3.9 (c 1.0 in CHCl3).
3.5.2. (R)-Ethyl 3-(N-benzyl-N-((R)-1-phenylethyl)-
amino)pentanoate 11b. Oil, yieldZ75%. 1H NMR d:
0.93 (t, 3H, JZ7.2 Hz, H-5), 1.11 (t, 3H, JZ7.2 Hz,
OCH2CH3), 1.28 (d, 3H, JZ6.9 Hz, CH(Ph)CH3), 1.40–
1.50 (m, 2H, H-4), 1.92 (d, 2H, JZ6.4 Hz, H-2), 3.12–3.21
(m, 1H, H-3), 3.46 (d, 1H, JZ14.9 Hz, CH2Ph), 3.71 (d, 1H,
JZ14.9 Hz, CH2Ph), 3.76 (q, 1H, JZ6.9 Hz, CH(Ph)CH3),
3.5.6. (R)-Ethyl 3-(N-benzyl-N-((R)-1-phenylethyl)-
amino)-3-phenylpropanoate 11g. Oil, yieldZ89%. 1H
NMR d: 0.96 (t, 3H, JZ6.9 Hz, OCH2CH3), 1.15 (d, 3H,
JZ6.7 Hz, CH(Ph)CH3), 2.47 (dd, 1H, JZ9.4, 14.6 Hz,
H-2), 2.58 (dd, 1H, JZ5.6, 14.6 Hz, H-2), 3.58 (d, 1H, JZ
14.6 Hz, CH2Ph), 3.66 (d, 1H, JZ14.6 Hz, CH2Ph), 3.65 (q,
2H, JZ6.9 Hz, OCH2CH3), 3.93 (q, 1H, JZ6.7 Hz,
CH(Ph)CH3), 4.36 (dd, 1H, JZ5.6, 9.4 Hz, H-3), 7.17–
7.33 (m, 15H, Ph). 13C NMR d: 14.1 (OCH2CH3), 16.0
(CH(Ph)CH3), 37.9 (C-2), 51.0 (CH2Ph), 57.0
(CH(Ph)CH3), 59.6 (C-3), 60.4 (OCH2CH3), 126.7, 126.9,
127.3, 127.9, 128.2, 128.3, 141.6, 141.9, 144.2 (Ph), 171.9
(C-1). Anal. Calcd for C29H25NO2: C, 80.59; H, 7.54; N,
3.61. Found: C, 80.94; H, 7.69; N, 3.87. [a]2D5 C6.8 (c 1.0 in
CHCl3).
3.87–4.00 (m, 2H, OCH2CH3), 7.15–7.40 (m, 10H, Ph). 13
C
NMR d: 12.1, 14.3 (C-5, OCH2CH3), 19.7 (CH(Ph)CH3),
26.4 (C-4), 36.9 (C-2), 50.1 (CH2Ph), 55.8 (C-3), 57.8
(CH(Ph)CH3), 60.2 (OCH2CH3), 126.7, 127.0, 128.1, 128.2,
128.4, 141.8, 143.2 (Ph), 173.1 (C-1). Anal. Calcd for
C22H29NO2: C, 77.83; H, 8.61; N, 4.12. Found: C, 77.52; H,
8.46; N, 3.87. [a]2D5 C4.3 (c 1.0 in CHCl3).
3.5.3. (R)-Ethyl 3-(N-benzyl-N-((R)-1-phenylethyl)-
1
amino)hexanoate 11c.24,25 Oil, yieldZ72%. H NMR d:
0.79 (t, 3H, JZ7.2 Hz, H-6), 1.11 (t, 3H, JZ7.2 Hz,
OCH2CH3), 1.15–1.21 (m, 1H, H-5), 1.26 (d, 3H, JZ
6.9 Hz, CH(Ph)CH3), 1.47–1.53 (m, 3H, H-4, H-5), 1.90
(dd, 1H, JZ8.2, 14.6 Hz, H-2), 1.97 (dd, 1H, JZ4.9,
14.6 Hz, H-2), 3.18–3.31 (m, 1H, H-3), 3.46 (d, 1H, JZ
14.9 Hz, CH2Ph), 3.71 (d, 1H, JZ14.9 Hz, CH2Ph), 3.75 (q,
1H, JZ6.9 Hz, CH(Ph)CH3), 3.89 (dq, 1H, JZ7.2, 10.7 Hz,
OCH2CH3), 3.94 (dq, 1H, JZ7.2, 10.7 Hz, OCH2CH3),
7.15–7.37 (m, 10H, Ph). 13C NMR d: 14.2, 14.3 (C-6,
OCH2CH3), 19.9 (CH(Ph)CH3), 20.3 (C-5), 36.0 (C-4), 37.0
(C-2), 50.2 (CH2Ph), 54.0 (C-3), 58.1 (CH(Ph)CH3), 60.2
(OCH2CH3), 126.7, 127.0, 127.4, 128.1, 128.2, 128.4,
142.0, 143.4 (Ph), 173.1 (C-1). [a]2D5 C4.1 (c 1.0 in CHCl3).
3.6. Synthesis of b-aminoesters 12
Cerium and ammonium nitrate (5.74 g, 10.5 mmol,
2.1 equiv) was added to b-amino ester 11 (5 mmol,
1 equiv) in a mixture of acetonitrile/water: 5:1 (50 mL) at
0 8C. After 1 h of stirring at room temperature, a saturated
aqueous solution of sodium carbonate (40 mL) was
introduced. The solid was filtered and washed with ether
(2!25 mL). The aqueous phase was separated and
extracted with ether (2!40 mL). The combined organic
phases were dried over MgSO4 and concentrated. The crude
product was purified by silica gel chromatography (cyclo-
hexane/ether: 70:30).
3.6.1. (R)-Ethyl 3-(N-((R)-1-phenylethyl)amino)butanoate
12a.26 Oil, yieldZ68%. 1H NMR d: 0.97 (d, 3H, JZ6.6 Hz,
H-4), 1.17 (t, 3H, JZ7.2 Hz, OCH2CH3), 1.24 (d, 3H, JZ
6.4 Hz, CH(Ph)CH3), 2.30 (dd, 1H, JZ6.4, 14.6 Hz, H2),
2.35 (dd, 1H, JZ5.6, 14.6 Hz, H-2), 2.86–2.94 (m, 1H,
H-3), 3.80 (q, 1H, JZ6.4 Hz, CH(Ph)CH3), 4.05 (q, 2H, JZ
7.2 Hz, OCH2CH3), 7.17–7.25 (m, 5H, Ph). 13C NMR d:
14.4 (OCH2CH3), 21.6 (C-4), 24.7 (CH(Ph)CH3), 41.0
(C-2), 47.9 (C-3), 55.1 (CH(Ph)CH3), 60.3 (OCH2CH3),
126.6, 127.0, 128.5, 146.2 (Ph), 172.4 (C-1). [a]2D5 C31.1
(c 1.0, CHCl3).
3.5.4. (R)-Ethyl 3-(N-benzyl-N-((R)-1-phenylethyl)-
amino)-4-methylpentanoate 11d. Oil, yieldZ82%. 1H
NMR d: 0.85 (d, 3H, JZ6.6 Hz, H-5), 1.08 (d, 3H, JZ
6.6 Hz, H-5), 1.20 (t, 3H, JZ7.2 Hz, OCH2CH3), 1.37 (d,
3H, JZ6.9 Hz, CH(Ph)CH3), 1.62–1.79 (m, 1H, H-4), 1.89
(dd, 1H, JZ2.3, 15.9 Hz, H-2), 2.06 (dd, 1H, JZ9.2,
15.9 Hz, H-2), 3.17–3.29 (m, 1H, H-3), 3.50 (d, 1H, JZ
14.8 Hz, CH2Ph), 3.75 (q, 1H, JZ6.9 Hz, CH(Ph)CH3),
3.78 (d, 1H, JZ14.8 Hz, CH2Ph), 4.04 (q, 2H, JZ7.2 Hz,
OCH2CH3), 7.18–7.50 (m, 10H, Ph). 13C NMR d: 14.3
(OCH2CH3), 19.7 (C-5), 20.3 (CH(Ph)CH3), 21.1 (C-5),
32.9 (C-4), 35.0 (C-2), 51.4 (CH2Ph), 58.1 (CH(Ph)CH3),
58.6 (C-3), 60.2 (OCH2CH3), 126.1, 126.7, 127.1, 128.7,
141.7, 142.4 (Ph), 173.4 (C-1). Anal. Calcd for C23H31NO2:
C, 78.15; H, 8.84; N, 3.96. Found: C, 78.42; H, 9.13; N,
4.22. [a]2D5 C5.3 (c 1.0 in CHCl3).
3.6.2. (R)-Ethyl 3-(N-((R)-1-phenylethyl)amino)-
pentanoate 12b. Oil, yieldZ66%. 1H NMR d: 0.78 (t,
3H, JZ7.4 Hz, H-5), 1.18 (t, 3H, JZ7.1 Hz, OCH2CH3),
1.24 (d, 3H, JZ6.4 Hz, CH(Ph)CH3), 1.31–1.38 (m, 2H, H-
4), 1.45 (s, 1H, NH), 2.28 (dd, 1H, JZ5.6, 14.6 Hz, H-2),
2.38 (dd, 1H, JZ5.9, 14.6 Hz, H-2), 2.60–2.69 (m, 1H, H-
3), 3.81 (q, 1H, JZ6.4 Hz, CH(Ph)CH3), 4.06 (q, 2H, JZ
7.1 Hz, OCH2CH3), 7.14–7.30 (m, 5H, Ph). 13C NMR d:
10.5 (C-5), 14.4 (OCH2CH3), 25.0 (CH(Ph)CH3), 28.1 (C-
4), 38.4 (C-2), 53.7 (C-3), 55.2 (CH(Ph)CH3), 60.3
(OCH2CH3), 126.8, 127.0, 128.5, 146.2 (Ph), 172.7 (C-1).
[a]2D5 C29.3 (c 1.0, CHCl3).
3.5.5. (R)-Ethyl 3-(N-benzyl-N-((R)-1-phenylethyl)-
amino)-4-phenylbutanoate 11e. Oil, yieldZ78%. 1H
NMR d: 1.09 (t, 3H, JZ7.2 Hz, OCH2CH3), 1.12 (d, 3H,
JZ6.9 Hz, CH(Ph)CH3), 2.03 (d, 2H, JZ6.9 Hz, H-4), 2.55
(dd, 1H, JZ6.9, 13.6 Hz, H-2), 2.79 (dd, 1H, JZ7.0,
13.6 Hz, H-2), 3.54–3.67 (m, 1H, H-3), 3.57 (d, 1H, JZ
14.8 Hz, CH2Ph), 3.76–3.98 (m, 3H, CH(Ph)CH3,
OCH2CH3), 3.82 (d, 1H, JZ14.8 Hz, CH2Ph), 7.09–7.32
(m, 15H, Ph). 13C NMR d: 14.2 (OCH2CH3), 19.0
(CH(Ph)CH3), 36.9 (C-4), 39.8 (C-2), 50.1 (CH2Ph), 56.6
(C-3), 57.8 (CH(Ph)CH3), 60.2 (OCH2CH3), 126.1, 126.8,
127.0, 128.0, 128.2, 128.3, 128.4, 128.6, 129.6, 140.1,
3.6.3. (R)-Ethyl 3-(N-((R)-1-phenylethyl)amino)-
1
hexanoate 12c.26b Oil, yieldZ63%. H NMR d: 0.72 (t,
3H, JZ6.9 Hz, H-6), 1.18 (t, 3H, JZ7.2 Hz, OCH2CH3),
1.11–1.29 (m, 10H, H-4, H-5), 1.24 (d, 3H, JZ6.4 Hz,