M. Kordes, M. Brands, M. Es-Sayed, A. de Meijere
FULL PAPER
of two diastereoisomers as a slightly yellow oil. IR (film): ν =
1 H, 1ЈЈ-H), 2.30 (d, 2J = 15 Hz, 1 H, 2-H), 2.93 (d, 2J = 15 Hz,
1 H, 2-H), 3.25 (t, 3J = 7 Hz, 2 H, 2ЈЈ-H), 3.71 (d, 2J = 14 Hz, 2 H,
NCH2Ph), 3.77 (s, 3 H, OCH3), 3.85 (d, 2J = 14 Hz, 2 H,
NCH2Ph), 4.44 (s, 2 H, OCH2Ph), 7.15–7.58 (m, 15 H, Ph-H) ppm.
˜
3029 cm–1, 2926, 2850, 1758 (C=O), 1732 (C=O), 745, 698. 1H
NMR (250 MHz, CDCl3), isomer 1: δ = 0.49 (dd, 2J = 6, 3J =
6 Hz, 1 H, cPr-H), 1.05–2.35 (m, 4 H, cPr-H, 1ЈЈ-H), 3.44–3.63 (m,
2 H, 2ЈЈ-H), 3.75 (s, 3 H, OCH3), 3.91 (s, 4 H, NCH2Ph), 4.21 (s, 13C NMR (62.6 MHz, CDCl3, DEPT): δ = 20.0 (–, cPr-C), 25.4 (+,
1 H, 2-H), 4.49 (s, 2 H, OCH2Ph), 7.08–7.43 (m, 15 H, Ph-H). Iso-
mer 2: δ = 0.88 (dd, J = 5, J = 5 Hz, 1 H, cPr-H), 1.05–2.35 (m,
cPr-C), 29.8 (–, C-1ЈЈ), 32.9 (–, C-2), 44.8 (Cquat, cPr-C), 51.5 (+,
OCH3), 56.2 (–, NCH2Ph), 69.8 (–, C-2ЈЈ), 72.7 (–, OCH2Ph), 126.6
2
3
4 H, cPr-H, 1ЈЈ-H), 3.44–3.63 (m, 2 H, 2ЈЈ-H), 3.74 (s, 3 H, OCH3), (+, Ph-C), 127.4 (+, Ph-C), 127.5 (+, Ph-C), 127.9 (+, Ph-C), 128.2
3.96 (s, 4 H, NCH2Ph), 4.50 (s, 2 H, OCH2Ph), 4.71 (s, 1 H, 2-H), (+, Ph-C), 128.9 (+, Ph-C), 138.5 (Cquat, Ph-C), 140.1 (Cquat, Ph-
7.08–7.43 (m, 15 H, Ph-H) ppm. 13C NMR (62.9 MHz, CDCl3, C), 173.7 (Cquat, COO) ppm. MS (70 eV): m/z (%) = 352 (Ͻ1)
DEPT), isomer 1: δ = 23.6 (–, cPr-C), 29.2 (+, cPr-C), 29.4 (–, C- [M+ – CH2 Ph], 107 (9) [OCH2 Ph+ ], 91 (100) [CH2 Ph+ ].
1ЈЈ), 51.1 (Cquat, cPr-C), 52.8 (+, OCH3), 56.6 (–, NCH2Ph), 62.1
(+, C-2), 69.8 (–, C-2ЈЈ), 72.8 (–, OCH2Ph), 126.5 (+, Ph-C), 126.6
(+, Ph-C), 127.6 (+, Ph-C), 128.3 (+, Ph-C), 128.7 (+, Ph-C), 128.8
C29H33NO3: calcd. 443.2460 (correct mass).
Compound 12b: A solution of 11b (10.10 g, 21.77 mmol) in THF
(500 mL) was treated with water (8 mL) and freshly prepared zinc/
copper couple[19] (25 g). The reaction mixture was stirred for 12 h,
filtered through Celite, and the solvent evaporated under reduced
pressure. The residue was taken up in Et2O (250 mL), the solution
washed with saturated NaCl solution (150 mL) and dried with
MgSO4. Purification by column chromatography on silica gel
(200 g), eluting with light petroleum/Et2O/NEt3, 9:1:0.01, yielded
(+, Ph-C), 138.4 (Cquat, Ph-C), 139.7 (Cquat, Ph-C), 169.1 (Cquat
,
COO). Isomer 2: δ = 23.2 (–, cPr-C), 26.0 (+, cPr-C), 29.5 (–, C-
1ЈЈ), 50.4 (Cquat, cPr-C), 52.9 (+, OCH3), 56.6 (–, NCH2Ph), 64.3
(+, C-2), 69.8 (–, C-2ЈЈ), 72.9 (–, OCH2Ph), 126.5 (+, Ph-C), 126.6
(+, Ph-C), 127.6 (+, Ph-C), 128.3 (+, Ph-C), 128.7 (+, Ph-C), 128.8
(+, Ph-C), 138.4 (Cquat, Ph-C), 139.0 (Cquat, Ph-C), 169.5 (Cquat
,
COO) ppm. MS (70 eV): m/z (%) = 442 (Ͻ1) [M+ – Cl], 386 (Ͻ1)
[M+ – CH2Ph], 91 (100) [CH2Ph+]. C29H32ClNO3 (478.0): calcd.
C 72.87, H 6.75; found C 72.53, H 6.84.
12b (5.88 g, 63%) as a colorless oil. IR (film): ν = 3028 cm–1, 2851,
˜
1739 (ester), 1453, 1209 (OCH2Ph), 1075 (OCH2Ph), 699. 1H NMR
2
3
(250 MHz, CDCl3): δ = 0.58 (dd, J = 5, J = 6 Hz, 1 H, cPr-H),
2
3
Compound 11b: Compound 7b (5.88 g, 22.0 mmol) was converted
by the same method as described above for 7a to yield 11b (8.07 g,
79%, light petroleum/Et2O, 10:1, Rf = 0.18) in a 1:2.3 mixture of
0.91 (dd, J = 5, J = 10 Hz, 1 H, cPr-H), 1.32 (mc, 1 H, cPr-H),
2.39 (d, 2J = 15 Hz, 1 H, 2-H), 2.91 (d, 2J = 15 Hz, 1 H, 2-H), 3.36
(mc, 2 H, 1ЈЈ-H), 3.74 (s, 3 H, OCH3), 3.77 (d, 2J = 13 Hz, 2 H,
NCH2Ph), 3.87 (d, 2J = 13 Hz, 2 H, NCH2Ph), 4.46 (s, 2 H,
OCH2Ph), 7.12–7.45 (m, 15 H, Ph-H) ppm. 13C NMR (62.9 MHz,
CDCl3, DEPT): δ = 19.5 (–, cPr-C), 26.9 (+, cPr-C), 33.2 (–, C-2),
45.1 (Cquat, cPr-C), 51.7 (+, OCH3), 56.1 (–, NCH2Ph), 69.8 (–, C-
1ЈЈ), 72.5 (–, OCH2Ph), 126.7 (+, Ph-C), 127.4 (+, Ph-C), 127.5 (+,
Ph-C), 127.9 (+, Ph-C), 128.3 (+, Ph-C), 128.9 (+, Ph-C), 138.5
(Cquat, Ph-C), 140.0 (Cquat, Ph-C), 173.6 (Cquat, COO) ppm.
MS (70 eV): m/z (%) = 429 (3) [M+], 398 (4) [M+ – OCH3], 356 (2)
[M+ – CH2COOCH3], 338 (94) [M+ – CH2Ph], 91 (100) [CH2Ph+].
C28H31NO3 (429.6): calcd. C 78.29, H 7.27, N 3.26; found C 78.32,
H 7.35, N 3.23.
diastereoisomers as a slightly yellow oil. IR (film): ν = 3028 cm–1,
˜
2951, 2855, 1756 (C=O), 1734 (C=O), 1454, 1272, 746 (C–Harom.),
1
698 (C–Harom.). H NMR (250 MHz, CDCl3), isomer 1: δ = 1.24
(dd, 2J = 5.7, 3J = 5.7 Hz, 1 H, cPr-H), 1.45 (dd, 2J = 5.7, 3J =
9.7 Hz, 1 H, cPr-H), 1.59–1.80 (m, 1 H, cPr-H), 3.51–3.85 (m, 2 H,
1ЈЈ-H), 3.75 (s, 3 H, OCH3), 3.94 (br. s, 4 H, NCH2Ph), 4.41 (s,
1 H, 2-H), 4.51 (s, 2 H, OCH2Ph), 7.10–7.48 (m, 15 H, Ph-H) ppm.
Isomer 2: δ = 0.79 (dd, 2J = 5.7, 3J = 5.7 Hz, 1 H, cPr-H), 1.20
3
(dd, 2J = 5.7, J = 9.7 Hz, 1 H, cPr-H), 1.59–1.80 (m, 1 H, cPr-H),
3.51–3.85 (m, 2 H, 1ЈЈ-H), 3.73 (s, 3 H, OCH3), 3.99 (br. s, 4 H,
NCH2Ph), 4.49 (s, 2 H, OCH2Ph), 4.86 (s, 1 H, 2-H), 7.10–7.48 (m,
15 H, Ph-H) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT), isomer
1: δ = 21.4 (–, cPr-C), 27.6 (+, cPr-C), 50.1 (Cquat, cPr-C), 52.8 (+,
OCH3), 56.6 (–, NCH2Ph), 63.9 (+, C-2), 68.0 (–, C-1ЈЈ), 72.8 (–,
OCH2Ph), 126.5 (+, Ph-C), 127.5 (+, Ph-C), 127.8 (+, Ph-C), 128.2
(+, Ph-C), 128.4 (+, Ph-C), 128.7 (+, Ph-C), 138.0 (Cquat, Ph-C),
139.7 (Cquat, Ph-C), 169.2 (Cquat, COO). Isomer 2: δ = 22.3 (–, cPr-
C), 30.9 (+, cPr-C), 51.1 (Cquat, cPr-C), 52.8 (+, OCH3), 56.5 (–,
NCH2Ph), 61.3 (+, C-2), 68.3 (–, C-1ЈЈ), 72.6 (–, OCH2Ph), 126.5
(+, Ph-C), 127.5 (+, Ph-C), 127.8 (+, Ph-C), 128.2 (+, Ph-C), 128.4
(+, Ph-C), 128.7 (+, Ph-C), 138.2 (Cquat, Ph-C), 139.5 (Cquat, Ph-
C), 169.0 (Cquat, COO) ppm. MS (70 eV): m/z (%) = 428 (9)
[M+ – Cl], 372 (Ͻ1) [M+ – CH2 Ph], 91 (100) [CH2 Ph+ ].
C28H30ClNO3 (464.0): calcd. C 72.48, H 6.52; found C 72.58,
H 6.57.
Compound 13a. From 12a: Hydrogen was purged through a solu-
tion of 12a (3.53 g, 7.96 mmol) and palladium on charcoal (10%,
600 mg) in MeOH (50 mL). The solution was stirred under hydro-
gen at ambient pressure for 3 d. The catalyst was filtered off
through a plug of Celite, and the filtrate concentrated under re-
duced pressure. Minor impurities were removed by a second fil-
tration through a short layer of silica gel eluting with methanol.
Evaporation of the solvent yielded 13a (1.11 g, 81%) as a colorless
oil. IR (film): ν = 3365 cm–1 (N–H), 1744 (C=O), 1001 (C–OH).
˜
2
3
1H NMR (250 MHz, D2O): δ = 0.33 (dd, J = 6, J = 6 Hz, 1 H,
cPr-H), 0.86 (dd, 2J = 6, 3J = 10 Hz, 1 H, cPr-H), 0.93–1.09 (m,
1 H, cPr-H), 1.20–1.37 (m, 1 H, 1Ј-H), 1.50–1.70 (m, 1 H, 1ЈЈ-H),
2.56 (mc, 2 H, 2-H), 3.52 (t, 3J = 7 Hz, 2 H, 2ЈЈ-H), 3.63 (s, 3 H,
OCH3) ppm. 13C NMR (125.7 MHz, D2O): δ = 17.1 (–, cPr-C),
20.8 (+, cPr-C), 31.1 (–), 34.1 (–), 37.7 (Cquat, cPr-C), 52.6 (+,
OCH3), 61.5 (–, C-2ЈЈ), 174.7 (Cquat, COO) ppm. MS (70 eV):
m/z (%) = 172 (4) [M+ – H], 142 (82) [M+ – OCH3], 128 (100) [M+ –
EtO]. C8H15NO3: calcd. 173.1051 (correct mass).
Compound 12a: A solution of 11a (13.31 g, 27.84 mmol) in THF
(400 mL) was treated with water (10 mL) and freshly prepared zinc/
copper couple[19] (30 g). The reaction mixture was stirred for 12 h,
filtered through Celite, and the solvent evaporated under reduced
pressure. The residue was dissolved in Et2O (300 mL), the solution
washed with saturated Na2CO3 solution (200 mL) and dried with
MgSO4. Purification by column chromatography on silica gel
(250 g), eluting with light petroleum/Et2O/NEt3, 9:1:0.01, yielded
Compound 13b. From 12b: Hydrogen was purged through a solution
of 12b (4.81 g, 11.2 mmol) and palladium on charcoal (10%, 2.0 g)
in MeOH (80 mL). The solution was stirred under hydrogen at am-
12a (7.64 g, 62%) as a slightly yellow oil. IR (film): ν = 3029 cm–1, bient pressure for 4 d. The catalyst was filtered off through a plug
˜
2850, 1736 (C=O), 1267, 734, 697. 1H NMR (250 MHz, CDCl3): δ
of Celite, and the filtrate concentrated under reduced pressure.
= 0.38 (dd, J = 4, J = 5 Hz, 1 H, cPr-H), 0.85 (mc, 1 H, cPr-H), Minor impurities were removed by a second filtration through a
0.78–0.97 (m, 1 H, cPr-H), 1.21–1.42 (m, 1 H, 1ЈЈ-H), 1.42–1.60 (m, short layer of silica gel eluting with methanol. Evaporation of the
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 3008–3016