G
P. Pomarański, Z. Czarnocki
Paper
Synthesis
(S)-2-[(R)-2-Nitro-1-phenylethyl]cyclopentanone (6a)
13C NMR (75 MHz, CDCl3): = 20.2, 28.0, 38.6, 43.7, 50.7, 55.8, 55.9,
78.3, 111.2, 111.3, 119.9, 130.0, 148.5, 149.0, 218.5.
HRMS (ESI+): m/z [M + H]+ calcd for C15H20NO5: 294.1341; found:
294.1345.
[]D25 –25.1 (c = 1 g/100 mL, CHCl3) for an enantiomerically enriched
sample of 99:1 dr (>98% ee). Enantiomeric purity was determined by
HPLC analysis in comparison with authentic racemic material [OD-H
column, n-hexanes/i-PrOH (80:20), 1.0 mL/min, 254 nm]; tR (major
enantiomer) = 14.8 min, tR (minor enantiomer) = 20.1 min.
Yield: 49 mg, 0.21 mmol (69%); brown oil.
1H NMR (300 MHz, CDCl3): = 7.36–7.24 (m, 3 H), 7.20–7.13 (m, 2 H),
5.33 (dd, J = 12.8, 5.5 Hz, 1 H), 4.71 (dd, J = 12.8, 9.9 Hz, 1 H), 3.75–
3.62 (m, 1 H), 2.44–2.29 (m, 2 H), 2.19–2.06 (m, 1 H), 1.97–1.82 (m, 2
H), 1.77–1.65 (m, 1 H), 1.55–1.41 (m, 1 H).
13C NMR (75 MHz, CDCl3): = 20.2, 28.3, 38.6, 44.1, 50.4, 78.2, 127.8,
128.0, 128.9, 137.7, 218.5.
HRMS (ESI+): m/z [M + H]+ calcd for C13H16NO3: 234.1130; found:
234.1128.
(S)-2-[(R)-2-Nitro-1-phenylethyl]cyclohexanone (6e)
[]D20 –22.5 (c = 1 g/100 mL, CHCl3) for an enantiomerically enriched
sample of 91:9 dr (>98% ee). Enantiomeric purity was determined by
HPLC analysis in comparison with authentic racemic material [OD-H
column, n-hexanes/i-PrOH (90:10), 1.0 mL/min, 254 nm]; tR (major
enantiomer) = 24.8 min, tR (minor enantiomer) = 33.7 min.
Yield: 69 mg, 0.28 mmol (93%); white solid; mp 129–130 °C.
1H NMR (300 MHz, CDCl3): = 7.36–7.25 (m, 3 H), 7.20–7.14 (m, 2 H),
4.94 (dd, J = 12.5, 4.5 Hz, 1 H), 4.63 (dd, J = 12.5, 9.9 Hz, 1 H), 3.76 (td,
J = 9.9, 4.5 Hz, 1 H), 2.75–2.63 (m, 1 H), 2.54–2.32 (m, 2 H), 2.14–2.02
(m, 1 H), 1.84–1.49 (m, 4 H), 1.32–1.14 (m, 1 H).
(S)-2-[(R)-2-Nitro-1-p-tolylethyl]cyclopentanone (6b)
13C NMR (75 MHz, CDCl3): = 25.0, 28.5, 33.2, 42.7, 43.9, 52.5, 78.9,
127.8, 128.2, 128.9, 137.8, 211.9.
Yield: 44 mg, 0.18 mmol (60%); brown oil.
HRMS (ESI+): m/z [M + H]+ calcd for C14H18NO3: 248.1287; found:
248.1280.
[]D25 –21.1 (c = 1 g/100 mL, CHCl3) for an enantiomerically enriched
sample of >99:1 dr (>98% ee). Enantiomeric purity was determined by
HPLC analysis in comparison with authentic racemic material [OD-H
column, n-hexanes/i-PrOH (90:10), 1.0 mL/min, 254 nm]; tR (major
enantiomer) = 11.4 min, tR (minor enantiomer) = 17.2 min.
1H NMR (300 MHz, CDCl3): = 7.13–7.03 (m, 4 H), 5.29 (dd, J = 12.7,
5.6 Hz, 1 H), 4.68 (dd, J = 12.8, 9.9 Hz, 1 H), 3.72–3.62 (m, 1 H), 2.28–
2.24 (m, 2 H), 2.31 (s, 3 H), 2.18–2.05 (m, 1 H), 1.96–1.83 (m, 2 H),
1.77–1.62 (m 1 H), 1.55–1.41 (m, 1 H).
13C NMR (75 MHz, CDCl3): = 20.2, 21.0, 28.2, 38.6, 43.8, 50.5, 78.4,
127.8, 128.3, 129.5, 129.6, 134.6, 137.5, 218.6.
HRMS (ESI+): m/z [M + H]+ calcd for C14H18NO3: 248.1287; found:
248.1280.
(S)-2-[(R)-2-Nitro-1-p-tolylethyl]cyclohexanone (6f)
[]D21 –20.1 (c = 1 g/100 mL, CHCl3) for an enantiomerically enriched
sample of >99:1 dr (>98% ee). Enantiomeric purity was determined by
HPLC analysis in comparison with authentic racemic material [OD-H
column, n-hexanes/i-PrOH (80:20), 1.0 mL/min, 254 nm]; tR (major
enantiomer) = 8.2 min, tR (minor enantiomer) = 10.8 min.
Yield: 78 mg, 0.297 mmol (99%); white solid; mp 124–126 °C.
1H NMR (300 MHz, CDCl3): = 7.15–7.09 (m, 2 H), 7.07–7.02 (m, 2 H),
4.92 (dd, J = 12.4, 4.6 Hz, 1 H), 4.60 (dd, J = 12.4, 9.9 Hz, 1 H), 3.72 (td,
J = 10.0, 4.6 Hz, 1 H), 2.73–2.61 (m, 1 H), 2.51–2.34 (m, 2 H), 2.31 (s, 3
H), 2.12–2.01 (m, 1 H), 1.83–1.47 (m, 4 H), 1.30–1.14 (m, 1 H).
(S)-2-[(R)-1-(2-Chlorophenyl)-2-nitroethyl]cyclopentanone (6c)
13C NMR (75 MHz, CDCl3): = 21.0, 25.0, 28.5, 33.1, 42.7, 43.5, 52.5,
79.0, 128.0, 129.6, 134.5, 137.4, 212.0.
Yield: 58 mg, 0.22 mmol (73%); glassy solid.
HRMS (ESI+): m/z [M + H]+ calcd for C15H20NO3: 262.1443; found:
262.1447.
[]D25 –30.3 (c = 1 g/100 mL, CHCl3) for an enantiomerically enriched
sample >99:1 dr (>98% ee). Enantiomeric purity was determined by
HPLC analysis in comparison with authentic racemic material [OD-H
column, n-hexanes/i-PrOH (90:10), 1.0 mL/min, 254 nm]; tR (major
enantiomer) = 8.84 min, tR (minor enantiomer) = 15.1 min.
1H NMR (300 MHz, CDCl3): = 7.25–7.10 (m, 4 H), 5.38 (dd, J = 9.5, 5.9
Hz, 1 H), 4.67 (dd, J = 13.0, 5.9 Hz, 1 H), 3.52–3.46 (m, 1 H), 2.31–2.19
(m, 2 H), 2.15–2.04 (m, 1 H), 1.95–1.81 (m, 2 H), 1.78–1.67 (m, 1 H),
1.62–1.56 (m, 1 H).
13C NMR (75 MHz, CDCl3): = 25.0, 30.4, 39.4, 47.9, 50.8, 77.3, 128.4,
128.6, 129.6, 130.0, 136.2, 143.0, 218.8.
HRMS (ESI+): m/z [M + H]+ calcd for C13H15ClNO3: 268.0740; found:
268.0738.
(S)-2-[(R)-1-(2-Chlorophenyl)-2-nitroethyl]cyclohexanone (6g)
[]D25 –27.1 (c = 1 g/100 mL, CHCl3) for an enantiomerically enriched
sample of 98:2 dr (98% ee). Enantiomeric purity was determined by
HPLC analysis in comparison with authentic racemic material [OD-H
column, n-hexanes/i-PrOH (80:20), 1.0 mL/min, 254 nm]; tR (major
enantiomer) = 14.2 min, tR (minor enantiomer) = 20.4 min.
Yield: 82 mg, 0.29 mmol (98%); yellow oil.
1H NMR (300 MHz, CDCl3): = 7.40–7.35 (m, 1 H), 7.27–7.17 (m, 3 H),
4.90 (d, J = 6.9 Hz, 2 H), 4.30 (dt, J = 10.1, 6.9 Hz, 1 H), 2.99–2.84 (m, 1
H), 2.54–2.29 (m, 2 H), 2.18–2.03 (m, 1 H), 1.87–1.52 (m, 4 H), 1.43–
1.23 (m, 1 H).
(S)-2-[(R)-1-(3,4-Dimethoxyphenyl)-2-nitroethyl]cyclopentanone
13C NMR (75 MHz, CDCl3): = 25.2, 28.5, 33.0, 42.8, 51.7, 77.2, 127.4,
(6d)
128.9, 130.3, 134.5, 135.4, 211.6.
HRMS (ESI+): m/z [M + H]+ calcd for C14H17ClNO3: 282.0897; found:
Yield: 76 mg, 0.26 mmol (85%); brown oil.
1H NMR (300 MHz, CDCl3): = 6.82–6.78 (m, 1 H), 6.75–6.67 (m, 2 H),
5.26 (dd, J = 12.7, 5.7 Hz, 1 H), 4.69 (dd, J = 12.7, 9.9 Hz, 1 H), 3.86 (s, 3
H), 3.85 (s, 3 H), 3.71–3.63 (m, 1 H), 2.41–2.29 (m, 2 H), 2.17–2.04 (m,
1 H), 1.97–1.87 (m, 2 H), 1.79–1.64 (m, 1 H), 1.59–1.45 (m, 1 H).
282.0890.
[]D25 –45.5 (c = 1 g/100 mL, CHCl3) for an enantiomerically enriched
sample of >99:1 dr (>98% ee). Enantiomeric purity was determined by
HPLC analysis in comparison with authentic racemic material [OD-H
column, n-hexanes/i-PrOH (90:10), 1.0 mL/min, 254 nm]; tR (major
enantiomer) = 10.3 min, tR (minor enantiomer) = 18.2 min.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–M