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N. Graf 6. Keyserlingk, J. Martens / Tetrahedron: Asymmetry 12 (2001) 2213–2222
2.74 (1H, dd, J 13.7 and J 8.8, H1%), 2.98 (1H, m, H3),
3.08 (1H, m, H3), 3.31 (1H, dd, J 13.7 and J 5.5, H1%),
4.55 (1H, m, H5), 7.18–7.33 (6H, m, arom.-H, pyridyl-
H), 7.74 (1H, dt, J 7.7 and J 1.6; pyridyl.-H), 8.15 (1H,
d, J 7.7, pyridyl-H), 8.63 (1H, d, J 4.9, pyridyl-H); 13C
NMR (CDCl3): l (ppm)=27.82 (C4), 34.68 (C3), 42.34
(C1%), 74.80 (C5), 122.02, 124.57, 126.07, 128.23, 129.36,
136.23, 149.06 (arom.-C, pyridyl-C), 139.34 (q.-arom.-
C), 153.26 (q.-pyridyl-C), 174.29 (C2); MS (CI, i-
butane): m/z (%)=237 (100) [MH+]. Anal. calcd for
C16H16N2 (236.1): C, 81.32; H, 6.82; N, 11.85. Found:
C, 81.12; H, 6.73; N, 11.81%.
4.17. (all-R)-(N-tert-Butyloxycarbonyl)-2%-aminocyclo-
pent-1%-yl-(2-N-methylpyrrolyl)-ethanone (all-R)-24
Reaction of 2-N-methylpyrrolyllithium (from N-
methylpyrrole (0.98 g, 12.1 mmol) and n-butyllithium
(11 mmol) according to Ref. 12) with N-Boc-lactam
(all-R)-16 (2.25 g (10 mmol) as described in general
procedure 1; column chromatography with n-hex-
ane:ethyl acetate:triethylamine 4:1:0.01, Rf value 0.36;
yield: 1.56 g (51%) colourless oil which solidified on
standing; mp 98°C; [h]2D0=+33.3 (c=1.10, CH2Cl2); IR
(KBr): w (cm−1)=3290 (N-H), 2950 (CH3, CH2), 1690
1
(CꢀO); H NMR (CDCl3): l (ppm)=1.17–2.06 (6H, m,
2×H3%, 2×H4%, 2×H5%), 1.42 (9H, s, C(CH3)3), 2.52 (2H,
m, H1, H2%), 3.02 (1H, d, J 10.9, H1), 3.93 (3H, s,
N-CH3), 4.08 (1H, m, H1%), 4.52 (1H, s, N-H), 6.10
(1H, m, pyrrolyl-H), 6.78 (1H, m, pyrrolyl.-H), 6.94
(1H, d, J 3.0, pyrrolyl-H); 13C NMR (CDCl3): l
(ppm)=21.60, 29.26, 32.10 (C3%, C4%, C5%), 28.35
(C(CH3)3), 37.61 (N-CH3), 39.27 (C2%), 39.84 (C1),
54.52 (C1%), 79.15 (C(CH3)3), 107.77, 119.01, 130.76
(pyrrolyl-C), 130.96 (q.-pyrrolyl-C), 155.58 (CꢀO),
190.82 (C1); MS (CI, i-butane): m/z (%)=307 (100)
[MH+]. Anal. calcd for C17H26N2O3 (306.2): C, 66.64;
H, 8.55; N, 9.14. Found: C, 66.50; H, 8.61; N, 8.99%.
4.15. (S)-2-(5-Phenylsulfanylmethyl-4,5-dihydro-3H-
pyrrol-2-yl)-pyridine (S)-22
Synthesised using general procedure 2 from crude (S)-
19 (8.47 g, 21.94 mmol); column chromatography with
n-hexane:ethyl acetate:triethylamine 4:1:0.02, Rf value
0.24; yield: 2.60 g (44%) yellow oil which solidified on
standing; mp 35–36°C; [h]2D0=+44.1 (c=1.89, CH2Cl2);
IR (KBr): w (cm−1)=2920 (CH2), 1610 CꢀN), 1565, 780,
1
730, 680 (C-H); H NMR (CDCl3): l (ppm)=1.85 (1H,
m, H4), 2.28 (1H, m, H4), 3.05 (1H, dd, J 13.2 and J
8.3, H1%), 3.08 (1H, m, H3), 3.24 (1H, m, H3), 3.52 (1H,
dd, J 13.2 and J 4.9, H1%), 4.51 (1H, m, H5), 7.10–7.47
(6H, m, arom.-H, pyridyl-H), 7.70 (1H, dt, J 7.9 and J
1.9, pyridyl-H), 8.05 (1H, d, J 7.9, pyridyl-H), 8.63 (1H,
d, J 4.1, pyridyl-H); 13C NMR (CDCl3): l (ppm)=
27.87 (C4), 35.11 (C3), 39.66 (C1%), 72.96 (C5), 122.15,
124.68, 136.20, 149.06 (pyridyl-C), 125.89, 128.80,
129.30 (arom.-C), 136.57 (q.-arom.-C), 152.96 (q.-
arom.-C), 175.14 (C2); MS (CI, i-butane): m/z (%)=
269 (100) [MH+]. Anal. calcd for C16H16N2S (268.1): C,
71.61; H, 6.01; N, 10.44; S, 11.95. Found: C, 71.51; H,
5.95; N, 10.33; S, 11.91%.
4.18. (all-R)-(N-tert-Butyloxycarbonyl)-2%-aminocyclo-
pent-1%-yl-(2-methylsulfanylphenyl)-ethanone (all-R)-25
2-Lithiumphenyllithiumthiolate was generated from
thiophenol (1.82 g, 16.5 mmol) and n-butyllithium (36
mmol) in anhydrous cyclohexane (25 mL) according to
Ref. 12. After adding anhydrous THF (25 mL) at 0°C
the solution was cooled to −78°C. At this temperature
lactam (all-R)-16 (3.38 g, 15 mmol) in anhydrous THF
(20 mL) was added. Stirring was continued for 4 h, then
the reaction mixture was allowed to warm up to −40°C
and stirred for 1 h at this temperature. The flask was
cooled again to −78°C and dimethylsulphate (2.08 g,
16.5 mmol) were added via syringe. Within 12 h the
reaction was warmed to room temperature. Work-up
was performed according to general procedure 1;
column chromatography with n-hexane:ethyl ace-
tate:triethylamine 4:1:0.02, Rf value 0.67; yield: 3.10 g
(59%) colourless oil; [h]2D0=+4.2 (c=1.15); IR (NaCl): w
(cm−1)=3300 (N-H), 2950 (CH3, CH2), 1680 (CꢀO),
750 (C-H); 1H NMR (CDCl3): l (ppm)=1.15–2.07 (6H,
m, 2×H3%, 2×H4%, 2×H5%), 1.43 (9H, s, C(CH3)3), 2.42
(3H, s, SCH3), 2.51 (1H, m, H2%), 2.76 (1H, m, H1),
3.30 (1H, d, J 15.5, H1), 4.16 (1H, m, H1%), 4.46 (1H, s,
N-H), 7.15 (1H, t, J 7.5, arom.-H), 7.30 (1H, m,
arom.-H), 7.47 (1H, m, arom.-H), 7.79 (1H, d, J 7.9,
arom.-H); 13C NMR (CDCl3): l (ppm)=16.00 (SCH3),
20.97, 29.22, 32.08 (C3%, C4%, C5%), 28.32 (C(CH3)3),
39.49 (C2%), 40.57 (C2), 54.43 (C1%), 79.10 (C(CH3)3),
123.47, 125.20, 130.03, 131.87 (arom.-C), 135.01, 141.93
(q.-arom.-H), 155.60 (CꢀO), 201.22 (C1); MS (CI, i-
butane): m/z=250 (100) [MH+−C4H8−CO2]. Anal.
calcd for C19H27NO3S (349.2): C, 65.30; H, 7.79; N,
4.01; S, 9.18. Found: C, 65.08; H, 7.80; N, 4.12; S,
9.15%.
4.16. (all-R)-(N-tert-Butyloxycarbonyl)-2%-aminocyclo-
pent-1%-yl-(2-thienyl)-ethanone (all-R)-23
Reaction of 2-thienyllithium (from thiophene (6.05 g,
72 mmol) and n-butyllithium (60 mmol) according to
Ref. 12) with N-Boc-lactam (all-R)-16 (11.25 g, 50
mmol) as described in general procedure 1; column
chromatography
with
n-hexane:ethyl
ace-
tate:triethylamine 4:1:0.01, Rf value 0.38; yield: 10.04 g
(65%) colourless oil which solidified on standing; mp
64°C; [h]2D0=+24.0 (c=1.065, CH2Cl2); IR (KBr): w
(cm−1)=3350 (N-H), 2950 (CH3, CH2), 1660 (C2O); H
1
NMR (CDCl3): l (ppm)=1.22–2.07 (6H, m, 2×H3%,
2×H4%, 2×H5%), 1.41 (9H, s, C(CH3)3), 2.54 (1H, m,
H1%), 2.67 (1H, m, H2), 3.18 (1H, m, H2), 4.09 (1H, m,
H2%), 4.52 (1H, s, N-H), 7.10 (1H, t, J 4.9, thienyl-H),
7.59 (1H, d, J 3.1, thienyl-H), 7.69 (1H, d, J 4.9,
thienyl-H); 13C NMR (CDCl3): l (ppm)=21.66, 29.14,
31.96 (C3%, C4%, C5%), 39.63 (C1%), 39.65 (C2), 54.29
(C2%), 79.09 (C(CH3)3), 127.95, 131.73, 133.23 (thienyl-
C), 144.50 (q.-thienyl-C), 155.55 (CꢀO), 192.77 (C1);
MS (CI, i-butane): m/z (%)=253 (100) [MH+−C4H8),
310 (40) [MH+]. Anal. calcd for C16H23NO3S (309.1): C,
62.11; H, 7.49; N, 4.53; S, 10.36. Found: C, 62.01; H,
7.60; N, 4.50; S, 10.12%.