268 JOURNAL OF CHEMICAL RESEARCH 2008
23.9, 22.7. MS–ESI (m/z): 212.1 (M+ + 2), 211.1 (M+ + 1), 210.2
(M+), 150.1. Anal. Calcd. for C11H18N2O2: C, 62.8; H, 8.6; N, 13.3.
Found: C, 62.9; H, 8.5; N, 13.2%.
J = 6.78 Hz, 1H), 4.46–4.42 (m, 1H), 4.36–4.27 (m, 1H), 4.21–4.04
(m, 2H), 3.62–3.48 (m, 2H), 2.46–2.16 (m, 1H), 2.07–1.84 (m, 6H),
1.17 (m, 3H). 13C NMR (75 MHz, CDCl3) G: 171.2, 169.9, 162.2,
66.7, 57.8, 46.9, 44.5, 27.1, 24.1, 20.8, 17.1. MS–ESI (m/z, relative
LQWHQVLW\ꢄꢇꢌꢒꢀꢋꢆꢐꢁꢈꢀꢂ0+ + 1), 225.1, 215.1 (20), 201.0, 184.1, 183.1
(100), 165.3, 153.9. Anal. Calcd. for C11H18N2O4: C, 54.5; H, 7.5; N,
11.6. Found: C, 54.8; H, 7.4; N, 11.6%.
(S)-1-formyl-N-(furan-2-ylmethyl)pyrrolidine-2-carboxamide
(6bꢌꢒꢀ&RORXUOHVVꢀOLTXLGꢀꢂꢆꢊꢇꢀ\LHOGꢌꢄꢀ>Į@D = – 87.4° (c 0.123, EtOAc).
1H NMR (300 MHz, CDCl3, 25°C, TMS) G: 8.25 (s, 1 H), 7.33 (m,
2H), 6.28 (t, J = 1.4 Hz, 1H), 6.18 (d, J = 3.1 Hz, 1H), 4.50–4.36
(m, 3H), 3.58–3.51 (m, 2H), 2.50–1.84 (m, 4H). 13C NMR (75 MHz,
CDCl3) G: 170.2, 162.2, 151.2, 142.0, 110.3, 107.1, 57.8, 46.9, 36.6,
27.1, 24.1. MS–ESI (m/z): 224.1 (M+ + 2), 223.2 (M+ + 1), 217.4,
211.2, 204.5, 195.1, 190.2, 174.0. Anal. Calcd. for C11H14N2O3: C,
59.45; H, 6.35; N, 12.6. Found: C, 59.6; H, 6.2; N, 12.8%.
(S)-methyl-2-((S)-1-formylpyrrolidine-2-carbonyl-amino)
propanoate (6kꢌꢒꢀ &RORXUOHVVꢀ OLTXLGꢀ ꢂꢆꢅꢇꢀ \LHOGꢌꢄꢀ >Į@D = –97.8° (c
0.100, EtOAc). 1H NMR (300 MHz, CDCl3, 25°C, TMS) G: 8.30 (s,
1H), 7.40 (s, 1H), 4.62–4.37 (m, 1H), 4.19–4.11 (m, 1H), 3.74 (s,
3H), 3.64–3.50 (m, 2H), 2.38–1.82 (m, 4H), 1.43 (m, 3H). 13C NMR
(75 MHz, CDCl3) G: 170.4, 166.4, 162.0, 59.2, 51.1, 46.8, 45.4, 28.1,
22.7, 17.8. MS–ESI (m/zꢄꢀUHODWLYHꢀLQWHQVLW\ꢄꢇꢌꢒꢀꢋꢋꢑꢁꢋꢀꢂ0+ + 1, 100),
228.1 (M+), 197.2, 183.2, 169.9, 154.1. Anal. Calcd. for C10H16N2O4:
C, 52.6; H, 7.1; N, 12.3. Found: C, 52.5; H, 7.2; N, 12.2%.
ꢀ6ꢁꢂ1ꢂꢀꢃꢂÀXRUREHQ]\OꢁꢂꢄꢂIRUP\OS\UUROLGLQHꢂꢅꢂFDUER[DPLGH (6c):
/LJKWꢀ \HOORZꢀ VROLGꢀ ꢂꢊꢊꢇꢀ \LHOGꢌꢄꢀ PꢁSꢁꢀ ꢈꢐꢉ±ꢈꢐꢑ°&ꢁꢀ >Į@D = –73.8°
(c 0.106, EtOAc). 1H NMR (300 MHz, CDCl3, 25°C, TMS)
G: 8.25 (s, 1H), 7.44 (s, 1H), 7.28–7.20 (m, 2H), 7.01–6.95 (m, 2H),
4.51–4.35 (m, 3H), 3.59–3.52 (m, 2H), 2.45–1.85 (m, 4H). 13C NMR
(75 MHz, CDCl3) G: 170.4, 162.2, 160.4, 133.9, 129.2, 115.5, 57.8,
46.9, 42.8, 27.3, 24.1. MS–ESI (m/z): 251.2 (M+ + 1), 246.5, 235.0,
217.1, 212.2, 204.6. Anal. Calcd. for C13H15FN2O2: C, 62.4; H, 6.0;
N, 11.2. Found: C, 62.6; H, 5.9; N, 11.1%.
(S)-dimethyl-2-((S)-1-formylpyrrolidine-2-carbonyl-amino)
succinate (6lꢌꢒꢀ:KLWHꢀVROLGꢀꢂꢊꢐꢇꢀ\LHOGꢌꢄꢀPꢁSꢁꢀꢉꢑ±ꢅꢈ°&ꢁꢀ>Į@D = –60.2°
1
(c 0.156, EtOAc). H NMR (300 MHz, CDCl3, 25°C, TMS) G: 8.30
(s, 1H), 7.49 (d, J = 7.80 Hz, 1H), 4.85 (m, 1H), 4.47 (m, 1H), 3.77
(s, 3H), 3.71 (s, 3H), 6.60 (m, 2H), 2.92 (m, 2H), 2.40–1.82 (m, 4H).
13C NMR (75 MHz, CDCl3) G: 171.2, 170.9, 170.5, 161.8, 57.8, 52.8,
52.1, 48.7, 46.8, 34.0, 27.8, 24.1. MS–ESI (m/zꢄꢀUHODWLYHꢀLQWHQVLW\ꢄꢇꢌꢒꢀ
288.0 (M+ + 2, 14), 287.0 (M+ + 1, 100), 259.0, 255.0 (19), 243.0,
227.0, 183.1, 160.1. Anal. Calcd. for C12H18N2O6: C, 50.35; H, 6.3;
N, 9.8. Found: C, 50.6; H, 6.2; N, 9.7%.
(S)-N-(4-chlorobenzyl)-1-formylpyrrolidine-2-carboxamide (6d):
:KLWHꢀVROLGꢀꢂꢊꢈꢇꢀ\LHOGꢌꢄꢀPꢁSꢁꢀꢈꢈꢆ±ꢈꢈꢍ°&ꢁꢀ>Į@D = –66.4° (c 0.106,
1
EtOAc). H NMR (300 MHz, CDCl3, 25°C, TMS) G: 8.27 (s, 1H),
7.42 (s, 1H), 7.33–7.24 (m, 2H), 7.19–7.15 (m, 2H), 4.59–4.36 (m,
3H), 3.60–3.53 (m, 2H), 2.50–1.86 (m, 4H). 13C NMR (75 MHz,
CDCl3) G: 170.3, 162.2, 136.7, 133.0, 128.7, 127.4, 57.9, 46.9, 42.9,
27.0, 24.1. MS–ESI (m/z): 267.2 (M+ + 1), 246.3, 239.1, 233.3, 231.1,
211.0, 198.1, 150.4. Anal. Calcd. for C13H15ClN2O2: C, 58.5; H, 5.7;
N, 10.5. Found: C, 58.6; H, 5.5; N, 10.6%.
(S)-dimethyl-2-((S)-1-formylpyrrolidine-2-carbonyl-amino)
pentanedioate (6mꢌꢒꢀ:KLWHꢀVROLGꢀꢂꢐꢉꢇꢀ\LHOGꢌꢄꢀPꢁSꢁꢀꢍꢑ±ꢉꢈ°&ꢁꢀ>Į@D
=
1
–44.4° (c 0.120, EtOAc). H NMR (300 MHz, CDCl3, 25°C, TMS)
G: 8.29 (s, 1H), 7.39 (d, J = 7.47 Hz, 1H), 4.55–4.45 (m, 2H), 3.72
(s, 3H), 3.64 (s, 3H), 3.58 (m, 2H), 2.40–1.87 (m, 8H). 13C NMR
(75 MHz, CDCl3) G: 173.0, 171.8, 170.4, 161.9, 57.7, 52.4, 51.9,
51.6, 46.8, 29.7, 27.4, 27.0, 24.1. MS–ESI (m/zꢄꢀUHODWLYHꢀLQWHQVLW\ꢄꢇꢌꢒꢀ
302.1 (M+ + 2, 27), 301.1 (M+ + 1, 100), 279.1 (21), 258.4, 242.4
(31), 194.9, 169.0, 150.3. Anal. Calcd. for C13H20N2O6: C, 52.0; H,
6.7; N, 9.3. Found: C, 52.1; H, 6.6; N, 9.2%.
(S)-1-formyl-N-phenethylpyrrolidine-2-carboxamide
(6e):
&RORXUOHVVꢀ OLTXLGꢀ ꢂꢊꢆꢇꢀ \LHOGꢌꢄꢀ >Į@D = –75.2° (c 0.104, EtOAc).
1H NMR (300 MHz, CDCl3, 25°C, TMS) G: 8.21 (s, 1H), 7.34–
7.15 (m, 5H), 6.94 (s, 1H), 4.53–4.42 (m, 1H), 3.58–3.43 (m, 4H),
2.86–2.78 (m, 2H), 2.51–1.86 (m, 4H). 13C NMR (75 MHz, CDCl3)
G: 170.4, 162.1, 139.9, 128.7, 128.4, 126.3, 57.8, 46.7, 40.7, 35.5,
26.9, 24.0. MS–ESI (m/z): 245.2 (M+ –1), 235.1, 221.1, 217.1, 200.3,
185.3, 169.2, 157.3. Anal. Calcd. for C14H18N2O2: C, 68.3; H, 7.4; N,
11.4. Found: C, 68.5; H, 7.2; N, 11.25%.
(S)-methyl-2-((S)-1-formylpyrrolidine-2-carbonyl-amino)-2-
phenylacetate (6nꢌꢒꢀ :KLWHꢀ VROLGꢀ ꢂꢆꢋꢇꢀ \LHOGꢌꢄꢀ PꢁSꢁꢀ ꢍꢍ±ꢍꢅ°&ꢁꢀ >Į@D
=
1
+ 40.1° (c 0.156, EtOAc). H NMR (300 MHz, CDCl3, 25°C, TMS)
G: 8.29 (s, 1H), 8.01 (d, J = 5.91 Hz, 1H), 7.35 (m, 5H), 5.49 (d,
J = 6.93 Hz, 1H), 4.63–4.60 (m, 1H), 3.73 (s, 3H), 3.60–3.48 (m, 2H),
2.48–1.86 (m, 4H). 13C NMR (75 MHz, CDCl3) G: 170.9, 169.8, 162.2,
140.0, 128.9, 128.5, 127.1, 57.7, 56.9, 52.8, 46.9, 27.0, 24.1. MS–ESI
(m/zꢄꢀUHODWLYHꢀLQWHQVLW\ꢄꢇꢌꢒꢀꢋꢑꢋꢁꢎꢀꢂ0+ + 2, 14), 291.0 (M+ + 1, 100),
259.0 (18), 243.0 (85), 231.0 (38), 183.1 (100), 180.9, 160.1. Anal.
Calcd. for C15H18N2O4: C, 62.1; H, 6.25; N, 9.65. Found: C, 62.3; H,
6.1; N, 9.6%.
(S)-1-formyl-N-p-tolylpyrrolidine-2-carboxamide (6f): White solid
ꢂꢍꢍꢇꢀ \LHOGꢌꢄꢀ PꢁSꢁꢀ ꢈꢊꢎ±ꢈꢊꢋ°&ꢁꢀ >Į@D = –128.4° (c 0.102, EtOAc).
1H NMR (300 MHz, CDCl3, 25°C, TMS) G: 9.28 (s, 1H), 8.33 (s, 1H),
7.38 (d, J = 8.40 Hz, 2H), 7.07 (d, J = 8.13 Hz, 2H), 4.76–4.65 (m,
1H), 3.64–3.56 (m, 2H), 2.62–2.58 (m, 1H), 2.28 (s, 3H), 2.13–1.82
(m, 3H). 13C NMR (75 MHz, CDCl3) G: 167.9, 162.6, 135.5, 133.6,
129.3, 119.7, 60.3, 47.0, 26.5, 24.1, 20.7. MS–ESI (m/z): 233.0 (M+
+ 1), 230.2, 212.2, 197.2, 187.2, 174.3. Anal. Calcd. for C13H16N2O2:
C, 67.2; H, 6.9; N, 12.1. Found: C, 67.3; H, 6.9; N, 12.1%.
(S)-N-(4-chlorophenyl)-1-formylpyrrolidine-2-carboxamide (6g):
&RORXUOHVVꢀ OLTXLGꢀ ꢂꢐꢍꢇꢀ \LHOGꢌꢄꢀ >Į@D = –105.6° (c 0.10, EtOAc).
1H NMR (300 MHz, CDCl3, 25°C, TMS) G: 9.56 (s, 1H), 8.34 (s, 1H),
7.41 (d, J = 8.82 Hz, 2H), 7.18 (d, J = 8.82 Hz, 2H), 4.69–4.65 (m, 1H),
3.65–3.60 (m, 2H), 2.56–1.76 (m, 4H). 13C NMR (75 MHz, CDCl3) G:
168.2, 162.6, 136.7, 129.0, 128.7, 120.8, 58.8, 47.2, 26.8, 24.2. MS–
ESI (m/zꢄꢀUHODWLYHꢀLQWHQVLW\ꢄꢇꢌꢒꢀꢋꢊꢐꢁꢐꢀꢂ0+ + 1, 29), 251.2 (M+ –1, 100),
227.0 (10), 223.3, 220.1, 195.3, 167.1. Anal. Calcd. for C12H13ClN2O2:
C, 57.0; H, 5.2; N, 11.1. Found: C, 57.25; H, 5.25; N, 11.0%.
(S)-methyl-2-((S)-1-formylpyrrolidine-2-carbonyl-amino)-3-
phenylpropanoate (6oꢌꢒꢀ&RORXUOHVVꢀOLTXLGꢀꢂꢐꢑꢇꢀ\LHOGꢌꢄꢀ>Į@D = –37.3°
1
(c 0.126, EtOAc). H NMR (300 MHz, CDCl3, 25°C, TMS) G: 8.10
(s, 1H), 7.31–6.99 (m, 6H), 4.80 (m, 1H), 4.41 (m, 1H), 3.67 (s, 3H),
3.46–2.96 (m, 4H), 2.26–1.76 (m, 4H). 13C NMR (75 MHz, CDCl3)
G: 171.7, 170.2, 162.0, 136.0, 129.3, 129.0, 128.6, 128.2, 126.9, 57.5,
53.3, 52.3, 46.6, 37.8, 27.1, 23.9. MS–ESI (m/zꢄꢀUHODWLYHꢀLQWHQVLW\ꢄꢇꢌꢒꢀ
306.0 (M+ + 2, 7), 305.0 (M+ + 1, 42), 289.1, 277.1 (100), 257.3, 227.2
(10), 211.3, 199.3 (17). Anal. Calcd. for C16H20N2O4: C, 63.1; H, 6.6;
N, 9.2. Found: C, 63.3; H, 6.6; N, 9.2%.
(S)-2-((S)-1-formylpyrrolidine-2-carbonyl-amino)-3-methylbutyl
acetate (6hꢌꢒꢀ&RORXUOHVVꢀOLTXLGꢀꢂꢋꢉꢇꢀ\LHOGꢌꢄꢀ>Į@D = –101.5° (c 0.104,
EtOAc). 1H NMR (300 MHz, CDCl3, 25°C, TMS) G: 8.28 (s, 1H), 7.05
(d, J = 8.61 Hz, 1H), 4.46 (m, 1H), 4.11 (m, 2H), 4.08 (m, 1H), 3.55
(m, 2H), 2.50–1.81 (m, 8H), 0.89 (m, 6H). 13C NMR (75 MHz, CDCl3)
G: 172.0, 171.1, 163.0, 65.2, 58.8, 54.4, 47.8, 30.3, 27.9, 25.1, 23.8,
21.7, 19.6. MS–ESI (m/z): 272.0 (M+ + 2), 271.1 (M+ + 1), 267.3,
242.9, 225.4, 212.1, 211.2, 194.0. Anal. Calcd. for C13H22N2O4: C,
57.8; H, 8.2; N, 10.4. Found: C, 57.6; H, 8.35; N, 10.4%.
(S)-methyl-3-(4-acetoxyphenyl)-2-((S)-1-formylpyrrolidine-2-
carbonyl-amino) propanoate (6pꢌꢒꢀ&RORXUOHVVꢀOLTXLGꢀꢂꢆꢈꢇꢀ\LHOGꢌꢄꢀ>Į@D
= –37.4° (c 0.324, EtOAc). 1H NMR (300 MHz, CDCl3, 25°C, TMS)
G: 8.13 (s, 1H), 7.75 (s, 1H), 6.93 (m, 2H), 6.72 (m, 2H), 4.78 (m, 1H),
4.45 (m, 1H), 3.73 (m, 3H), 3.50–2.91 (m, 4H), 2.26–1.82 (m, 7H). 13
C
NMR (75 MHz, CDCl3) G: 172.8, 172.2, 171.3, 163.1, 156.6, 131.3,
127.8, 116.3, 58.6, 54.5, 53.2, 47.8, 37.9, 28.6, 24.9, 23.1. MS–ESI
(m/zꢄꢀUHODWLYHꢀLQWHQVLW\ꢄꢇꢌꢒꢀꢐꢍꢆꢁꢋꢀꢂ0+ + 2, 100), 355.1 (10), 333.2 (35),
319.2 (55), 279.9, 227.0, 185.2. Anal. Calcd. for C18H22N2O6: C, 59.7;
H, 6.1; N, 7.7. Found: C, 59.5; H, 6.2; N, 7.6%.
(S)-2-((1-formyl-pyrrolidine-2-carboyl)-amino)-propane-1,3-diyl
diacetate (6iꢌꢒꢀ&RORXUOHVVꢀOLTXLGꢀꢂꢈꢊꢇꢀ\LHOGꢌꢄꢀ>Į@D = –63.4° (c 0.142,
(S)-methyl-2-((S)-1-formylpyrrolidine-2-carbonyl-amino)-3-(1H-
indol-2-yl) propanoate (6qꢌꢒꢀ <HOORZꢀ VROLGꢀ ꢂꢆꢍꢇꢀ \LHOGꢌꢄꢀ PꢁSꢁꢀ ꢈꢋꢎ±
122°&ꢁꢀ>Į@D = –0° (c 0.156, EtOAc). 1H NMR (300 MHz, CDCl3,
25°C, TMS) G: 10.80 (s, 1H), 8.46 (s, 1H), 7.99 (s, 1H), 7.53 (d,
J = 7.74 Hz, 1H), 7.35 (m, 1H), 7.21–7.08 (m, 3H), 4.93–4.89 (m,
1H), 4.43 (m, 1H), 3.71 (s, 3H), 3.45–3.26 (m, 4H), 2.35–1.75 (m,
4H). 13C NMR (75 MHz, CDCl3) G: 172.2, 172.0, 161.8, 136.0,
127.6, 123.7, 121.7, 119.1, 118.4, 111.3, 109.5, 57.6, 53.1, 52.4, 46.6,
31.7, 29.2, 23.9. MS–ESI (m/zꢄꢀUHODWLYHꢀLQWHQVLW\ꢄꢇꢌꢒꢀꢐꢆꢊꢁꢈꢀꢂ0+ + 2,
5), 344.1 (M+ + 1, 35), 328.1 (16), 317.1 (24), 316.1 (100), 266.2,
219.0, 196.2. Anal. Calcd. for C18H21N3O4: C, 63.0; H, 6.2; N, 12.2.
Found: C, 62.9; H, 6.2; N, 12.4%.
1
EtOAc). H NMR (300 MHz, CDCl3, 25°C, TMS) G: 8.29 (s, 1H),
7.44 (d, J = 7.80 Hz, 1H), 4.51–4.47 (m, 1H), 4.43–4.36 (m, 1H),
4.24–4.13 (m, 4H), 3.58 (m, 2H), 2.52–2.47 (m, 1H), 2.10 (s, 6H),
2.06–1.86 (m, 3H). 13C NMR (75 MHz, CDCl3) G: 170.8, 170.2,
162.3, 62.7, 57.8, 47.5, 46.8, 26.8, 24.1, 20.7. MS–ESI (m/z, relative
LQWHQVLW\ꢄꢇꢌꢒꢀꢐꢎꢋꢁꢈꢀꢂ0+ + 2, 19), 301.1 (M+ + 1, 100), 279.0 (24),
259.0, 241.1, 216.1, 198.1, 157.8. Anal. Calcd. for C13H20N2O6: C,
52.0; H, 6.7; N, 9.3. Found: C, 51.8; H, 6.9; N, 9.25%.
(S)-2-((S)-1-formylpyrrolidine-2-carbonyl-amino)propyl acetate
(6jꢌꢒꢀ&RORXUOHVVꢀOLTXLGꢀꢂꢆꢊꢇꢀ\LHOGꢌꢄꢀ>Į@D = –85.6° (c 0.128, EtOAc).
1H NMR (300 MHz, CDCl3, 25°C, TMS) G: 8.29 (s, 1H), 7.09 (d,