The Journal of Organic Chemistry
Article
7.18−7.40 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 12.5, 23.1, 28.4,
29.6, 44.3, 55.8, 118.5, 127.5, 127.6 (2C), 128.6 (2C), 136.1, 174.7; MS
(ESI, m/z) 229 (M + H+, 100%). Anal. Calcd for C14H16N2O: C, 73.66;
H, 7.06; N, 12.27. Found: C, 73.59; H, 7.10; N, 12.48.
1-Benzyl-5-[2-(ethyloxycarbonyl)propyl]-pyrrolidin-2-one
(10d). Following the general protocol A, the SmI2 mediated cross-
coupling of hemiaminal 9 with ethyl methacrylate afforded 10d-H (less
polar diastereomer) in 27% yield and 10d-L (more polar diastereomer)
in 46% yield.
(4S,5R)-1-Benzyl-4-benzyloxy-5-[2-(ethyloxycarbonyl)ethyl]-
pyrrolidin-2-one (15a). Following the general protocol B, the SmI2-
mediated cross-coupling of sulfone 18 with ethyl acrylate afforded 15a in
90% yield as a colorless oil: [α]20D +41.3 (c 1.2, CHCl3); IR (film) 3022,
2931, 1733, 1695, 1456, 1091 cm−1; 1H NMR (400 MHz, CDCl3) δ 1.21
(t, J = 7.2 Hz, 3H), 1.59−1.70 (m, 1H), 1.95−2.05 (m, 1H), 2.15−2.31
(m, 2H), 2.54 (dd, J = 2.4, 17.6 Hz, 1H), 2.74 (ddd, J = 0.8, 6.4, 17.6 Hz,
1H), 3.49 (ddd, J = 2.0, 3.2, 8.8 Hz, 1H), 3.86 (ddd, J = 2.0, 2.4, 6.4 Hz,
1H), 3.98 (d, J = 15.2 Hz, 1H), 4.09 (q, J = 7.2 Hz, 2H), 4.39 (d, J = 12.0
Hz, 1H), 4.46 (d, J = 12.0 Hz, 1H), 5.05 (d, J = 15.2 Hz, 1H), 7.19−7.39
(m, 10H); 13C NMR (100 MHz, CDCl3) δ 14.0, 25.7, 29.5, 37.1, 43.9,
60.6, 62.1, 70.5, 75.4, 127.4, 127.5 (2C), 127.8 (2C), 127.9 (2C), 128.4
(2C), 128.6, 136.0, 137.2, 172.3, 172.4; MS (ESI m/z) 382 (M + H+).
Anal. Calcd for C23H27NO4: C, 72.42; H, 7.13; N, 3.67. Found: C, 72.38;
H, 7.30; N, 3.58.
10d-H. Colorless oil: 1H NMR (400 MHz, CDCl3) δ 1.08 (d, J = 6.9
Hz, 3H), 1.25 (t, J = 7.1 Hz, 3H), 1.64−1.85 (m, 3H), 2.03−2.15 (m,
1H), 2.33−2.46 (m, 2H), 2.47−2.58 (m, 1H), 3.38−3.49 (m, 1H), 3.92
(d, J = 15.1 Hz, 1H), 4.05−4.18 (m, 2H), 5.02 (d, J = 15.1 Hz, 1H),
7.18−7.38 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 14.1, 17.2, 23.9,
30.0, 35.8, 36.5, 44.0, 55.0, 60.7, 127.5 (2C), 128.0 (2C), 128.6, 136.5,
174.9, 176.0.
(4S,5R)-1-Benzyl-4-Benzyloxy-5-[2-(tert-butyloxycarbonyl)-
ethyl]-pyrrolidin-2-one (15b). Following the general protocol B, the
SmI2-mediated cross-coupling of sulfone 18 with tert-butyl acrylate
afforded 15b in 75% yield as a colorless oil: [α]20D +34.7 (c 1.2, CHCl3);
10d-L. Colorless oil: 1H NMR (400 MHz, CDCl3) δ 1.11 (d, J = 7.1
Hz, 3H), 1.16 (t, J = 7.2 Hz, 3H), 1.23−1.32 (m, 1H), 1.61−1.70 (m,
1H), 2.07−2.25 (m, 2H), 2.32−2.54 (m, 3H), 3.32−3.41 (m, 1H),
3.95−4.08 (m, 2H), 4.02 (d, J = 15.0 Hz, 1H), 4.95 (d, J = 15.0 Hz, 1H),
7.22−7.35 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 14.1, 18.5, 24.2,
29.9, 36.2, 37.2, 44.1, 55.4, 60.5, 127.4 (2C), 128.1 (2C), 128.6, 136.7,
174.8, 175.5.
10d. Data: IR (film) 3028, 2982, 2921, 1729, 1688, 1417, 1255, 1188
cm−1; MS (ESI, m/z) 290 (M + H+). Anal. Calcd for C17H23NO3: C,
70.56; H, 8.01; N, 4.84. Found: C, 70.24; H, 7.66; N, 5.08.
(E) and (Z)-1-Benzyl-5-[2-(ethyloxycarbonyl)ethenyl]-pyrroli-
din-2-one (10e). Following the general protocol A, the SmI2 mediated
cross-coupling of hemiaminal 9 with ethyl propiolate afforded 10e as an
inseparable diastereomeric mixture (E:Z = 1.6:1) in a combined yield of
49% as a colorless oil: IR (film) 3020, 2983, 2927, 1718, 1693, 1414,
1190, 1037 cm−1; MS (ESI, m/z) 274 (M + H+). Anal. Calcd for
C16H19NO3: C, 70.31; H, 7.01; N, 5.12. Found: C, 70.04; H, 6.89; N,
5.48.
(Z)-10e-H. Less polar diastereomer, data read from spectrum of the
diastereomeric mixture: 1H NMR (400 MHz, CDCl3) δ 1.23 (t, J = 7.1
Hz, 3H), 1.67−1.79 (m, 1H), 2.30−2.58 (m, 3H), 4.05 (d, J = 14.8 Hz,
1H), 4.10 (q, J = 7.1 Hz, 2H), 4.79 (d, J = 14.8 Hz, 1H), 5.14−5.22 (m,
1H), 5.83 (dd, J = 1.0, 11.5 Hz, 1H), 6.02 (dd, J = 9.1, 11.5 Hz, 1H),
7.18−7.34 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 14.0, 24.8, 30.0,
45.2, 55.2, 60.4, 122.2, 127.4, 128.3, 128.4, 136.5, 148.0, 165.2, 175.0.
(E)-10e-L. More polar diastereomer, data read from spectrum of the
diastereomeric mixture: 1H NMR (400 MHz, CDCl3) δ 1.31 (t, J = 7.1
Hz, 3H), 1.79−1.88 (m, 1H), 2.16−2.27 (m, 1H), 2.42−2.58 (m, 2H),
3.82 (d, J = 14.8 Hz, 1H), 4.00−4.15 (m, 1H), 4.22 (q, J = 7.1 Hz, 2H),
5.03 (d, J = 14.8 Hz, 1H), 5.86 (dd, J = 0.8, 15.6 Hz, 1H), 6.72 (dd, J =
8.2, 15.6 Hz, 1H) 7.18−7.34 (m, 5H); 13C NMR (100 MHz, CDCl3) δ
14.1, 24.6, 29.5, 44.6, 57.9, 60.7, 123.4, 127.6, 128.3, 128.7, 136.1, 145.8,
165.5, 174.7.
1
IR (film) 3125, 3030, 1725, 1693, 1406, 1148 cm−1; H NMR (400
MHz, CDCl3) δ 1.39 (s, 9H), 1.53−1.65 (m, 1H), 1.90−2.01 (m, 1H),
2.06−2.23 (m, 2H), 2.52 (dd, J = 2.0, 17.5 Hz, 1H), 2.73 (dd, J = 6.5,
17.5 Hz, 1H), 3.49 (ddd, J = 1.8, 3.0, 9.2 Hz, 1H), 3.85 (ddd, J = 1.8, 2.0,
6.5 Hz, 1H), 3.98 (d, J = 15.2 Hz, 1H), 4.38 (d, J = 12.0 Hz, 1H), 4.44 (d,
J = 12.0 Hz, 1H), 5.04 (d, J = 15.2 Hz, 1H), 7.18−7.34 (m, 10H); 13C
NMR (100 MHz, CDCl3) δ 25.6, 27.8 (3C), 30.6, 37.1, 43.8, 62.1, 70.3,
75.3, 80.7, 127.3 (2C), 127.4 (2C), 127.7 (2C), 128.3 (2C), 128.5 (2C),
136.0, 137.2, 171.5, 172.3; MS (ESI, m/z) 410 (M + H+). Anal. Calcd for
C25H31NO4: C, 73.32; H, 7.63; N, 3.42. Found: C, 73.48; H, 7.92; N,
3.58.
(4S,5R)-1-Benzyl-4-benzyloxy-5-(2-cyanoethyl)-pyrrolidin-2-
one (15c). Following the general protocol B, the SmI2-mediated cross-
coupling of sulfone 18 with acrylonitrile afforded (4S, 5S)-15c (less
polar diastereomer) in 6% yield and (4S,5R)-15c (more polar
diastereomer) in 69% yield.
(4S,5R)-15c-L. Colorless oil: [α]20D +45.9 (c 1.0, CHCl3); IR (film)
3031, 2930, 2250, 1692, 1448, 1356, 1091 cm−1; 1H NMR (400 MHz,
CDCl3) δ 1.58−1.68 (m, 1H), 1.94−2.03 (m, 1H), 2.11−2.28 (m, 2H),
2.55 (dd, J = 3.4, 17.4 Hz, 1H), 2.77 (dd, J = 6.8, 17.4 Hz, 1H), 3.52 (ddd,
J = 3.0, 3.0, 9.4 Hz, 1H), 3.91 (ddd, J = 3.0, 3.4, 6.8 Hz, 1H), 4.06 (d, J =
15.3 Hz, 1H), 4.42 (d, J = 11.7 Hz, 1H), 4.52 (d, J = 11.7 Hz, 1H), 4.93
(d, J = 15.3 Hz, 1H), 7.20−7.50 (m, 10H); 13C NMR (100 MHz,
CDCl3) δ 13.0, 26.9, 37.0, 44.4, 62.0, 70.9, 75.2, 118.5, 127.7 (2C), 127.8
(2C), 128.1 (2C), 128.6 (2C), 128.9 (2C), 135.7, 136.9, 172.2; MS
(ESI, m/z) 335 (M + H+). Anal. Calcd for C21H22N2O2: C, 75.42; H,
6.63; N, 8.38. Found: C, 75.04; H, 6.85; N, 8.22.
(4S,5R)-1-Benzyl-4-benzyloxy-5-[2-(ethyloxycarbonyl)-
propyl]pyrrolidin-2-one (15d). Following the general protocol B,
the SmI2-mediated cross-coupling of sulfone 18 with ethyl methacrylate
afforded 15d-H (less polar diastereomer) in 31% yield and 15d-L (more
1,1′-Dibenzyl-2,2′-bipyrrolidine-5,5′-dione (10f). Following
the general protocol A (in the absence of an α,β-unsaturated
compound), the SmI2-mediated homocoupling of hemiaminal 9
afforded 10f-H (less polar diastereomer) in 16.5% yield and 10f-L
(more polar diastereomer) in 16.5% yield, along with the reduced
product 11 in 65% yield.
polar diastereomer) in 46% yield.
1
15d-H. Colorless oil: [α]20 +65.2 (c 0.8, CHCl3); H NMR (400
D
MHz, CDCl3) δ 1.08 (d, J = 7.0 Hz, 3H), 1.22 (t, J = 7.1 Hz, 3H), 1.62
(ddd, J = 3.7, 7.0, 14.2 Hz, 1H), 1.83 (ddd, J = 7.0, 8.9, 14.2 Hz, 1H),
2.33−2.43 (m, 1H), 2.54 (dd, J = 2.1, 17.5 Hz, 1H), 2.78 (dd, J = 6.4,
17.5 Hz, 1H), 3.48 (ddd, J = 1.6, 3.7, 8.9 Hz, 1H), 3.89 (d, J = 15.4 Hz,
1H), 3.89 (ddd, J = 1.6, 2.1, 6.4 Hz, 1H), 4.02−4.15 (m, 2H), 4.37 (d, J =
11.7 Hz, 1H), 4.45 (d, J = 11.7 Hz, 1H), 5.09 (d, J = 15.4 Hz, 1H), 7.12−
7.40 (m, 10H); 13C NMR (100 MHz, CDCl3) δ 14.1, 17.6, 34.6, 36.0,
37.2, 43.9, 60.8, 61.1, 70.5, 76.2, 127.5 (2C), 127.8 (3C), 128.4 (3C),
10f-H. Colorless oil: 1H NMR (400 MHz, CDCl3) δ 1.61−1.73 (m,
2H), 2.00−2.12 (m, 2H), 2.42−2.54 (m, 4H), 3.50 (d, J = 15.3 Hz, 2H),
3.73 (dd, J = 4.9, 8.5 Hz, 2H), 5.19 (d, J = 15.3 Hz, 2H), 7.05−7.11 (m,
4H), 7.24−7.36 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 19.0 (2C),
29.8 (2C), 44.9 (2C), 57.1 (2C), 127.7 (3C), 127.8 (4C), 128.8 (3C),
135.7 (2C), 175.8 (2C).
1
128.6 (2C), 136.0, 137.3, 172.5, 175.7.
10f-L. White solid: mp 133.4−134.4 °C (EtOAc); H NMR (400
1
15d-L. Colorless oil: [α]20 +21.0 (c 1.2, CHCl3); H NMR (400
MHz, CDCl3) δ 1.56−1.78 (m, 4H), 2.35−2.53 (m, 4H), 3.72−3.80 (m,
2H), 3.78 (d, J = 14.8 Hz, 2H), 4.81 (d, J = 14.8 Hz, 2H), 6.93−7.06 (m,
4H), 7.23−7.33 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 17.0 (2C),
30.0 (2C), 44.9 (2C), 56.0 (2C), 127.7 (3C), 128.1 (4C), 128.7 (3C),
135.7 (2C), 175.1 (2C).
D
MHz, CDCl3) δ 1.09 (t, J = 7.1 Hz, 3H), 1.14 (d, J = 7.0 Hz, 3H), 1.22
(ddd, J = 3.4, 11.0, 14.0 Hz, 1H), 2.09 (ddd, J = 2.8, 11.2, 14.0 Hz, 1H),
2.38−2.48 (m, 1H), 2.51 (dd, J = 1.7, 17.5 Hz, 1H), 2.73 (ddd, J = 6.2,
17.4 Hz, 1H), 3.44 (ddd, J = 1.1, 2.8, 11.0 Hz, 1H), 3.83 (ddd, J = 1.1, 1.7,
6.2 Hz, 1H), 3.97 (d, J = 15.2 Hz, 1H), 3.99 (q, J = 7.1 Hz, 2H), 4.38 (d, J
= 12.4 Hz, 1H), 4.42 (d, J = 12.4 Hz, 1H), 5.04 (d, J = 15.2 Hz, 1H),
7.19−7.35 (m, 10H); 13C NMR (100 MHz, CDCl3) δ 14.0, 18.5, 34.6,
10f. Data: IR (KBr) 3018, 2921, 1686, 1408, 1250 cm−1; MS (ESI, m/
z) 349 (M + H+). Anal. Calcd for C22H24N2O2: C, 75.83; H, 6.94; N,
8.04. Found: C, 76.14; H, 7.28; N, 8.27.
G
dx.doi.org/10.1021/jo301277n | J. Org. Chem. XXXX, XXX, XXX−XXX