196
A. Noole et al. / Tetrahedron: Asymmetry 23 (2012) 188–198
For 4d0: 1H NMR (400 MHz, CDCl3) d 7.63 (d, J = 8.3 Hz, 2H), 7.37 (d,
J = 8.6 Hz, 2H), 7.27 (d, J = 8.5 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 5.18
(s, 1H), 4.82 (d, J = 5.8 Hz, 1H), 4.08–3.95 (m, 3H), 3.14 (dd, J = 11.4,
8.8 Hz, 1H), 3.08–2.97 (m, 1H), 2.39 (s, 3H), 2.32–2.18 (m, 2H), 1.14
(t, J = 7.1, 3H). 13C NMR (101 MHz, CDCl3) d 170.18, 149.35, 144.53,
137.49, 133.36, 129.92 (2), 127.96 (2), 127.88 (2), 121.62 (2),
119.22, 93.61, 66.78, 61.50, 51.32, 36.75, 31.55, 21.74, 14.17. HRMS
(ESI): calcd for [M+H]+ (C22H24F3N2O7S)+ requires m/z 517.1256,
found 517.1257.
(101 MHz, CDCl3) d 170.21, 144.27, 136.02, 133.74, 133.33,
133.26, 129.83 (2), 129.22, 128.30, 127.95, 127.80 (2), 126.82,
126.69, 125.74, 123.56, 93.70, 67.71, 61.39, 51.46, 36.73, 31.65,
21.74, 14.15. HRMS (ESI): calcd for [M+H]+ (C25H27N2O6S)+ requires
m/z 483.1590, found 483.1590.
4.4.8. Ethyl-2-(5-cyclohexyl-4-nitro-1-tosylpyrrolidin-3-yl)-
acetate 4g/4g0
Compounds 4g/4g0 (Table 3, entry 7) were synthesized accord-
ing to the general procedure from (E)-(2-nitrovinyl)cyclohexane
2g (47 mg) and (E)-ethyl 4-(4-methylphenylsulfonamido)but-2-
enoate 1b (28 mg, 0.1 mmol) to yield 42 mg of product (96% yield)
as a mixture of diastereoisomers (isomers were later separated via
silica gel column chromatography to obtain analytical data). The
diastereomeric ratio was determined by 1H NMR (dr 68/32), and
the enantiomeric excess by chiral HPLC (Chiralpak AD-H column,
1 mL/min, 15% iPrOH in hexane, 230 nm). For 4g 92% ee:
4.4.6. Ethyl-2-(4-nitro-5-(thiophen-2-yl)-1-tosylpyrrolidin-3-yl)-
acetates 4e/4e0
Compounds 4e/4e0 (Table 3, entry 5) were synthesized accord-
ing to the general procedure from (E)-2-(2-nitrovinyl)thiophene
2e (47 mg) and (E)-ethyl 4-(4-methylphenylsulfonamido)but-2-
enoate 1b (28 mg, 0.1 mmol) to yield 35 mg of product (80% yield)
as a mixture of diastereoisomers. The diastereomeric ratio was
determined by 1H NMR (dr 52/48), and the enantiomeric excess
by chiral HPLC (Chiralpak AD-H column, 1 mL/min, 20% iPrOH in
hexane, 230 nm). For 4e 97% ee: tR = 20.27 (major) and tR = 26.16
(minor). For 4e0 57% ee: tR = 27.66 (minor) and tR = 43.01 (major).
tR = 14.15 (major) and tR = 20.52 (minor); ½a D25
¼ ꢀ62 (c 0.10,
ꢂ
CHCl3). For 4g0 36% ee: tR = 15.17 (minor) and tR = 31.59 (major);
½
a 2D5
ꢂ
¼ ꢀ40 (c 0.07, CHCl3). IR
m = 2931, 2857, 1734, 1554, 1346,
1163, 1096, 1025, 818, 759, 668 cmꢀ1. For 4g: 1H NMR (400 MHz,
CDCl3) d 7.79 (d, J = 8.3 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 4.59 (dd,
J = 8.4, 5.1 Hz, 1H), 4.27 (t, J = 5.6 Hz, 1H), 4.10 (q, J = 7.2 Hz, 2H),
4.02 (dd, J = 12.8, 7.4 Hz, 1H), 3.04 (dd, J = 12.9, 11.0 Hz, 1H),
2.56–2.49 (m, 1H), 2.45 (s, 3H), 2.39–2.32 (m, 1H), 2.32–2.18 (m,
1H), 1.88–1.67 (m, 6H), 1.34–1.26 (m, 2H), 1.23 (t, J = 7.1 Hz, 3H),
1.19–1.13 (m, 1H), 1.10–0.97 (m, 2H). 13C NMR (101 MHz, CDCl3)
d 170.20, 144.43, 134.92, 130.16 (2), 127.83 (2), 91.23, 68.76,
61.27, 52.90, 42.83, 41.29, 34.55, 29.42, 27.95, 26.25, 26.02,
25.94, 21.77, 14.22. For 4g0: 1H NMR (400 MHz, CDCl3) d 7.72 (d,
J = 8.3 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 4.94 (d, J = 5.8 Hz, 1H),
4.14 (qt, J = 6.9, 3.6 Hz, 2H), 3.82 (d, J = 4.0 Hz, 1H), 3.81–3.77 (m,
1H), 3.01 (dd, J = 11.6, 8.1 Hz, 1H), 2.98–2.89 (m, 1H), 2.46 (s,
3H), 2.32 (dd, J = 17.4, 5.9 Hz, 1H), 2.20 (d, J = 8.2 Hz, 1H), 2.18–
2.12 (m, 1H), 1.96 (d, J = 12.0 Hz, 1H), 1.86–1.77 (m, 1H), 1.71 (t,
J = 13.9 Hz, 2H), 1.43–1.28 (m, 2H), 1.24 (t, J = 7.1 Hz, 3H), 1.16
(m, 1H), 1.02 (m, 1H), 0.76 (m, 1H). 13C NMR (101 MHz, CDCl3) d
170.47, 144.22, 132.68, 129.84 (2), 128.17 (2), 88.60, 69.99,
61.43, 51.73, 41.96, 38.05, 31.81, 30.54, 27.02, 26.43, 26.20,
26.06, 21.78, 14.23. HRMS (ESI): calcd for [M+H]+ (C21H31N2O6S)+
requires m/z 439.1903, found 439.1897.
IR
m ;
= 1732, 1555, 1354, 1165, 1098, 1028, 817, 711, 668 cmꢀ1
For 4e: 1H NMR (400 MHz, CDCl3) d 7.69 (m, 2H), 7.35–7.30 (m,
2H), 7.29–7.24 (m, 1H), 7.09 (m, 1H), 6.98 (m, 1H), 5.61 (d,
J = 4.7 Hz, 1H), 4.85 (dd, J = 7.0, 4.8 Hz, 1H), 4.20–4.07 (m, 2H),
4.05 (dd, J = 11.6, 7.8 Hz, 1H), 3.42 (dd, J = 11.6, 8.3 Hz, 1H), 2.88
(dq, J = 15.1, 8.0 Hz, 1H), 2.62–2.46 (m, 2H), 2.44 (s, 3H), 1.23 (t,
J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) d 170.20, 144.58,
142.98, 134.00, 130.06 (2), 127.96 (2), 127.43, 126.27, 126.21,
95.89, 63.38, 61.38, 52.50, 40.26, 35.30, 21.77, 14.20. For 4e0: 1H
NMR (400 MHz, CDCl3) d 7.69 (m, 2H), 7.35–7.30 (m, 2H), 7.29–
7.24 (m, 1H), 7.09 (m, 1H), 6.98 (m, 1H), 5.51 (s, 1H), 5.02 (d,
J = 5.9 Hz, 1H), 4.20–4.07 (m, 2H), 3.97 (dd, J = 8.6, 7.4 Hz, 1H),
3.30 (tt, J = 14.1, 7.6 Hz, 1H), 3.17 (dd, J = 11.3, 8.9 Hz, 1H), 2.45
(s, 3H), 2.34 (dd, J = 7.3, 5.5 Hz, 2H), 1.23 (t, J = 7.1 Hz, 3H). 13C
NMR (101 MHz, CDCl3) d 170.15, 144.32, 142.39, 133.74, 129.83
(2), 127.81 (2), 127.50, 126.07, 125.65, 93.47, 63.32, 61.45, 50.91,
37.28, 31.66, 21.77, 14.20. HRMS (ESI): calcd for [M+H]+
(C19H23N2O6S2)+ requires m/z 439.0998, found 439.0996.
4.4.7. Ethyl 2-(5-(naphthalen-2-yl)-4-nitro-1-tosylpyrrolidin-3-
yl)acetates 4f/4f0
Compounds 4f/4f0 (Table 3, entry 6) were synthesized according
to the general procedure from (E)-2-(2-nitrovinyl)naphthalene 2f
(60 mg) and (E)-ethyl 4-(4-methylphenylsulfonamido)but-2-eno-
ate 1b (28 mg, 0.1 mmol) to yield 45 mg of product (93% yield)
as a mixture of diastereoisomers. The diastereomeric ratio was
determined by 1H NMR (dr 58/42), and the enantiomeric excess
by chiral HPLC (Chiralpak AD-H column, 1 mL/min, 30% EtOH in
hexane, 230 nm). For 4f 95% ee: tR = 19.50 (major) and tR = 24.20
(minor). For 4f0 44% ee: tR = 30.53 (minor) and tR = 42.01 (major).
4.4.9. (Ethyl-2-((3S,4R,5S)-4-methyl-4-nitro-5-phenyl-1-tosyl-
pyrrolidin-3-yl)acetate 4h and ethyl-2-((3R,4R,5S)-4-methyl-
4-nitro-5-phenyl-1-tosylpyrrolidin-3-yl)acetate 4h0
At first, (E)-(2-nitroprop-1-en-1-yl)benzene 2h (49 mg, 0.3
mmol) and (E)-ethyl-4-(4-methylphenylsulfonamido)but-2-enoate
1b (28 g, 0.1 mmol) were dissolved in toluene (0.5 mL). Next, 1-
(3,5-bis(trifluoromethyl)phenyl)-3-((1S)-((2S,4S,5R)-5-ethylquinu-
clidin-2-yl)(6-methoxyquinolin-4-yl)methyl)thiourea II (12 mg,
20 mol %) was added and the mixture was stirred at 60 °C for
3 days. The mixture was purified directly by silica gel column chro-
matography using a mixture of heptane and EtOAc as eluent to
yield 33 mg (74%) of product as a mixture of diastereoisomers.
The diastereomeric ratio was determined by 1H NMR (dr 70/30),
and the enantiomeric excess by chiral HPLC (Chiralpak AD-H col-
umn, 1 mL/min, 30% EtOH in hexane, 230 nm). For 4h 63% ee:
IR
m = 1732, 1555, 1352, 1165, 1098, 1025, 910, 819, 735,
666 cmꢀ1. For 4f: 1H NMR (400 MHz, CDCl3) d 7.89–7.80 (m, 4H),
7.67 (d, J = 8.3 Hz, 2H), 7.54–7.47 (m, 2H), 7.43 (dd, J = 3.6,
1.7 Hz, 1H), 7.27 (d, J = 8.0 Hz, 2H), 5.44 (d, J = 5.2 Hz, 1H), 4.85
(dd, J = 7.0, 5.3 Hz, 1H), 4.17–4.04 (m, 3H), 3.55 (dd, J = 11.5,
8.0 Hz, 1H), 2.92 (dq, J = 15.0, 7.9 Hz, 1H), 2.49–2.44 (m, 2H), 2.41
(s, 3H), 1.20 (t, J = 7.1, 3H). 13C NMR (101 MHz, CDCl3) d 170.19,
144.51, 135.62, 133.93, 133.32, 133.21, 130.00 (2), 129.32,
128.28, 127.95, 127.80 (2), 126.75, 126.69, 125.87, 123.56, 95.81,
67.44, 61.33, 53.02, 39.99, 35.22, 21.71, 14.15. For 4f0: 1H NMR
(400 MHz, CDCl3) d 7.89–7.80 (m, 4H), 7.73 (d, J = 8.2 Hz, 2H),
7.53–7.49 (m, 2H), 7.42 (dd, J = 8.5, 1.8 Hz, 1H), 7.32 (d,
J = 8.1 Hz, 2H), 5.42 (s, 1H), 4.98 (d, J = 5.8 Hz, 1H), 4.16–4.05 (m,
3H), 3.30 (dd, J = 11.3, 8.9 Hz, 1H), 3.24–3.11 (m, 1H), 2.44 (s,
3H), 2.33 (dd, J = 7.4, 3.5 Hz, 2H), 1.20 (t, J = 7.1 Hz, 3H). 13C NMR
tR = 10.45 (major) and tR = 20.14 (minor); IR
m = 1732, 1599, 1555,
1351, 1161, 1097, 815 cmꢀ1. For 4h0 67% ee: tR = 14.95 (major)
and tR = 51.24 (minor). For 4h: 1H NMR (400 MHz, CDCl3) d 7.73
(d, J = 8.3 Hz, 2H), 7.41–7.23 (m, 7H), 5.35 (s, 1H), 4.19–4.08 (m,
3H), 3.33 (dd, J = 11.9, 10.3 Hz, 1H), 2.92 (tdd, J = 10.1, 8.0, 4.7 Hz,
1H), 2.47 (s, 3H), 2.38 (dd, J = 16.5, 4.7 Hz, 1H), 2.26 (dd, J = 16.5,
10.0 Hz, 1H), 1.24 (t, J = 7.1 Hz, 3H), 1.12 (s, 3H). 13C NMR
(101 MHz, CDCl3) d 170.24, 144.65, 136.09, 133.00, 130.15 (2),
128.80, 128.59 (2), 128.07 (2), 127.56 (2), 96.50, 70.97, 61.36,