1148
Q. Liang et al. / Tetrahedron: Asymmetry 25 (2014) 1146–1149
NMR (400 MHz, CDCl3): d 7.32–7.26 (m, 2H), 7.10–7.04 (m, 2H),
4.68 (d, J = 6.4 Hz, 1H), 4.13 (d, J = 6.0 Hz, 1H), 3.22 (br, 1H),
2.78–2.76 (m, 1H), 2.45–2.28 (m, 2H), 2.16–2.04 (m, 1H),
2.03–1.84 (m, 2H), 1.78–1.70 (m, 1H); 13C NMR (100 MHz, CDCl3):
d 212.1, 140.7, 133.9, 129.6, 128.1, 93.4, 81.5, 51.5, 43.4, 39.8, 36.0,
17.9; HPLC (Chiralcel OJ-H, hexanes/i-PrOH, 95:5, flow
rate = 1.0 mL/min, k = 254 nm): tmajor = 18.1 min, tminor = 21.8 min.
4.4. (1S,5S,6R,7S)-6-(4-Fluorophenyl)-1-hydroxy-7-nitrobicyclo-
[3.2.1]octan-8-one 4d6
Following the general procedure described above, 4d was
obtained after purification by flash chromatography (hexane/ethyl
acetate = 5:1) as a colorless oil (90% yield, 99% ee, dr = 9:1); 1H
NMR (400 MHz, CDCl3): d 7.15–7.09 (m, 2H), 7.05–6.96 (m, 2H),
4.69 (d, J = 5.6 Hz, 1H), 4.15 (d, J = 5.6 Hz, 1H), 3.28 (br, 1H),
2.78–2.73 (m, 1H), 2.46–2.28 (m, 2H), 2.18–2.05 (m, 1H), 2.02–
1.85 (m, 2H), 1.78–1.70 (m, 1H); 13C NMR (100 MHz, CDCl3): d
212.3, 138.1 (JC–F = 3.0 Hz), 128.4 (JC–F = 7.6 Hz), 116.3
(JC–F = 21.3 Hz), 93.6, 81.6, 51.7, 43.2, 39.7, 36.0, 17.9; HPLC (Chiral-
cel OJ-H, hexanes/i-PrOH, 95:5, flow rate = 1.0 mL/min,
k = 254 nm): tmajor = 64.3 min, tminor = 61.1 min.
Figure 1. ORTEP representation of 4k.
to 3 mol % without significantly affecting the stereoselectivity. Fur-
ther investigations are currently underway to expand the scope and
application of this efficient domino process.
4. Experimental
General reaction procedure. To a solution of bisoxazolidine 1
(9.3 mg, 0.025 mmol) in i-PrOH (1 mL) were added Ni(acac)2
(6.4 mg, 0.025 mmol), 1,2-cyclohexadione (67.2 mg, 0.6 mmol)
and nitroolefin (0.5 mmol). The reaction mixture was stirred at
room temperature for the time indicated in Tables 1 and 2. The
reaction mixture was concentrated and the residue was purified
by flash chromatography (hexane/ethyl acetate = 5:1) to afford
the product 4.
4.5. (1S,5S,6R,7S)-6-(2-Bromophenyl)-1-hydroxy-7-nitrobicyclo-
[3.2.1]octan-8-one 4e5b
Following the general procedure described above, 4e was
obtained after purification by flash chromatography (hexane/ethyl
acetate = 8:1) as a colorless oil (90% yield, 98% ee, dr = 2:1); 1H
NMR (400 MHz, CDCl3): d 7.60–7.58 (m, 1H), 7.33–7.26 (m, 1H),
7.16–7.10 (m, 1H), 7.01–6.97 (m, 1H), 5.07 (d, J = 6.0 Hz, 1H),
4.78 (d, J = 6.4 Hz, 1H), 3.28 (br, 1H), 2.61 (d, J = 4.8 Hz, 1H),
2.50–2.39 (m, 2H), 2.20–1.93 (m, 3H), 1.82–1.74 (m, 1H); 13C
NMR (100 MHz, CDCl3): d 212.3, 140.7, 133.7, 129.3, 128.6, 128.2,
123.7, 91.8, 81.8, 52.5, 43.2, 40.2, 36.4, 17.9; HPLC (Chiralcel OJ-
H, hexanes/i-PrOH, 90:10, flow rate = 1.0 mL/min, k = 254 nm):
tmajor = 25.7 min, tminor = 31.1 min.
4.1. (1S,5S,6R,7S)-1-Hydroxy-7-nitro-6-phenylbicyclo[3.2.1]oc-
tan-8-one 4a6
Following the general procedure described above, 4a was
obtained after purification by flash chromatography (hexane/ethyl
acetate = 5:1) as a colorless oil (99% yield, 99% ee, dr = 7:1). 1H
NMR (400 MHz, CDCl3): d 7.35–7.22 (m, 3H), 7.17–7.10 (m, 2H),
4.76 (d, J = 6.0 Hz, 1H), 4.15 (d, J = 5.6 Hz, 1H), 3.42 (br, 1H),
2.80–2.74 (m, 1H), 2.44–2.18 (m, 2H), 2.14–1.90 (m, 3H), 1.80–
1.66 (m, 1H); 13C NMR (100 MHz, CDCl3): d 212.7, 142.3, 129.3,
127.8, 126.7, 93.5, 81.7, 51.6, 43.9, 39.7, 36.0, 17.9; HPLC (Chiralcel
OJ-H, hexanes/i-PrOH, 90:10, flow rate = 1.0 mL/min, k = 254 nm):
tmajor = 13.2 min, tminor = 16.1 min.
4.6. (1S,5S,6R,7S)-6-(4-Methylphenyl)-1-hydroxy-7-nitrobicy-
clo-[3.2.1]octan-8-one 4f5b
Following the general procedure described above, 4f was
obtained after purification by flash chromatography (hexane/ethyl
acetate = 5:1) as a yellow solid (98% yield, 91% ee, dr = 7:1); 1H
NMR (400 MHz, CDCl3): d 7.12 (d, J = 7.6 Hz, 2H), 7.04–6.99 (m,
2H), 4.73 (d, J = 6.0 Hz, 1H), 4.12 (d, J = 6.4 Hz, 1H), 3.31 (br, 1H),
2.78–2.76 (m, 1H), 2.42–2.36 (m, 2H), 2.30 (s, 3H), 2.14–1.92 (m,
3H), 1.78–1.70 (m, 1H); 13C NMR (100 MHz, CDCl3): d 212.6,
139.4, 137.6, 130.0, 126.6, 93.8, 81.6, 51.7, 43.5, 39.8, 36.0, 21.0,
17.9; HPLC (Chiralcel IA, hexanes/i-PrOH, 90:10, flow rate =
1.0 mL/min, k = 254 nm): tmajor = 23.4 min, tminor = 15.5 min.
4.2. (1S,5S,6R,7S)-6-(4-Bromophenyl)-1-hydroxy-7-nitrobicyclo-
[3.2.1]octan-8-one 4b6
Following the general procedure described above, 4b was
obtained after purification by flash chromatography (hexane/ethyl
acetate = 8:1) as a colorless oil (88% yield, 92% ee, dr = 4:1); 1H
NMR (400 MHz, CDCl3): d 7.48–7.44 (m, 2H), 7.04–6.98 (m, 2H),
4.67 (d, J = 6.4 Hz, 1H), 4.12 (d, J = 6.0 Hz, 1H), 3.22 (br, 1H),
2.78–2.74 (m, 1H), 2.44–2.26 (m, 2H), 2.16–2.06 (m, 1H),
2.04–1.84 (m, 2H), 1.78–1.68 (m, 1H); 13C NMR (100 MHz, CDCl3):
d 212.1, 141.2, 132.5, 128.5, 121.9, 93.3, 81.5, 51.4, 43.4, 39.8, 36.0,
17.9; HPLC (Chiralcel OJ-H, hexanes/i-PrOH, 90:10, flow
rate = 1.0 mL/min, k = 254 nm): tmajor = 44.1 min, tminor = 55.8 min.
4.7. (1S,5S,6R,7S)-6-(4-Methoxyphenyl)-1-hydroxy-7-nitrobicy-
clo-[3.2.1]octan-8-one 4g5b
Following the general procedure described above, 4g was
obtained after purification by flash chromatography (hexane/ethyl
acetate = 5:1) as a colorless oil (95% yield, 90% ee, dr = 7:1); 1H
NMR (400 MHz, CDCl3): d 7.05 (d, J = 8.8 Hz, 2H), 6.83 (d, J = 8.8 Hz,
2H), 4.72 (d, J = 6.4 Hz, 1H), 4.10 (d, J = 5.6 Hz, 1H), 3.76 (s, 3H),
3.38 (s, 1H), 2.73 (d, J = 2.4 Hz, 1H), 2.44–2.27 (m, 2H), 2.14–2.00
(m, 1H), 2.00–1.90 (m, 2H), 1.77–1.66 (m, 1H); 13C NMR (100 MHz,
CDCl3): d 212.7, 159.0, 134.4, 127.8, 114.6, 93.9, 81.6, 55.3, 51.8,
43.2, 39.7, 36.0, 17.9; HPLC (Chiralcel AD-H, hexanes/i-PrOH,
80/20, flow rate = 1.0 mL/min, k = 254 nm): tmajor = 22.7 min,
tminor = 12.8 min.
4.3. (1S,5S,6R,7S)-6-(4-Chlorophenyl)-1-hydroxy-7-nitrobicyclo-
[3.2.1]octan-8-one 4c5b
Following the general procedure described above, 4c was
obtained after purification by flash chromatography (hexane/ethyl
acetate = 8:1) as a colorless oil (80% yield, 96% ee, dr = 7:1); 1H