6
M. Durmaz et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
NaBH3CN (49.0 mg, 0.78 mmol) was added, followed 15 min later
by AcOH (0.144 mL, 2.52 mmol). After stirring for 4 h at room tem-
perature, the reaction mixture was diluted with 2% CHCl3–CH3OH
(30 mL), and washed with 1 M NaOH (4 Â 25 mL). The aqueous
layer was re-extracted with CHCl3 (3 Â 20 mL), the combined
organic layer was dried over MgSO4 and the solvent was removed
under reduced pressure. The residue was purified by flash chro-
matography on silica gel eluting with CHCl3–MeOH mixtures. Pale
1.0 mL/min, wavelength = 210 nm: tR (major) = 18.4 min, tR
(minor) = 37.3 min]. [
25 = +132.6 (c 1.0, CHCl3).
a]
D
4.3.4. (S)-3-[1-(4-Bromophenyl)-2-nitroethyl)]-pentane-2,4-dione
11d17c
White solid; yield 78%; 78% ee; mp 71 °C; IR (cmÀ1): 1729,
1699, 1547, 1490, 1431, 1362, 1264, 1140, 818. 1H NMR
(400 MHz, CDCl3): d = 7.46 (d, J = 8.5 Hz, 2H), 7.07 (d, J = 8.4 Hz,
2H), 4.61–4.59 (m, 2H), 4.33 (d, J = 10.8 Hz, 1H), 4.24–4.18 (m,
1H), 2.30 (s, 3H), 1.98 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3):
d = 201.4, 200.6, 135.0, 132.5, 129.6, 122.7, 77.8, 70.4, 42.2, 30.5,
29.7 ppm. HPLC analysis [Chiralpak AS-H column, hexane–2-pro-
panol = 85:15, flow rate: 1.0 mL/min, wavelength = 210 nm: tR
yellow oil; 85% yield; [
a
]
D
25 = À3.2 (c 1.2, CHCl3); IR (cmÀ1): 3218,
2933, 2862, 1608, 1512, 1362, 1240, 1060, 734. 1H NMR
(400 MHz, CDCl3): d = 7.26–7.24 (m, 2H), 6.80–6.78 (m, 2H), 6.60
(br s, 2H), 4.09–3.97 (m, 3H), 3.69–3.48 (m, 3H), 2.41–2.28 (m,
2H), 2.18 (s, 6H), 2.00–1.58 (m, 5H), 1.25 (s, 9H), 1.16–0.98 (m,
3H) ppm; 13C NMR (100 MHz, CDCl3): d = 182.1, 156.2, 143.6,
126.2, 113.9, 66.8, 65.4, 55.7, 40.2, 34.0, 33.0, 31.5, 29.0, 25.0,
24.6, 21.6 ppm. Anal. Calcd for: C22H37N3OS (391.61): C, 67.47, H,
9.52, N, 10.73. Found: C, 67.24, H, 9.88, N, 10.71.
(major) = 17.7 min, tR (minor) = 32.5 min]. [a]
25 = +137.1 (c 1.0,
D
CHCl3).
4.3.5. (S)-3-[1-(2-Methoxyphenyl)-2-nitroethyl]-pentane-2,4-dione
11e17c
4.3. Representative procedure for the asymmetric addition of
2,4–pentanedione to nitroalkenes
Colorless oil; yield 97%; 72% ee; IR (cmÀ1): 1727, 1702, 1596,
1552, 1494, 1359, 1247, 1159, 1024, 758. 1H NMR (400 MHz,
CDCl3): d = 7.29–7.24 (m, 1H), 7.09–7.07 (m, 1H), 6.91–6.87 (m,
2H), 4.86–4.75 (m, 1H), 4.61–4.56 (m, 2H), 4.51–4.45 (m, 1H),
3.88 (s, 3H), 2.28 (s, 3H), 1.93 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3): d = 202.3, 201.5, 130.2, 129.7, 123.5, 121.2, 111.2, 69.1,
55.4, 38.9, 30.4, 29.7, 28.7 ppm. HPLC analysis [Chiralpak AD-H col-
umn, hexane–2-propanol = 97:3, flow rate: 0.5 mL/min, wave-
length = 210 nm: tR (major) = 38.4 min, tR (minor) = 40.6 min].
To a stirred solution of nitroalkene (0.05 mmol) and chiral
catalyst (0.005 mmol, 10 mol %) in 0.125 mL of solvent was added
2,4-pentanedione (0.1 mmol). After the reaction was complete
(monitored by TLC), the resulting mixture was concentrated and
the residue was purified through column chromatography on silica
gel (eluent, ethyl acetate/hexane 1:4 to 1:1) to afford product
11a–11l. The enantiomeric purity of the product was determined
by using chiral HPLC analysis. Racemic samples of the Michael
adducts were prepared using a racemic catalyst.
[a]
25 = +186.1 (c 0.5, CHCl3).
D
4.3.6. (S)-3-[1-(3-Methoxyphenyl)-2-nitroethyl]-pentane-2,4-
dione 11f17c
4.3.1. (S)-3-(2-Nitro-1-phenylethyl)-pentane-2,4-dione 11a17a
White solid; yield 99%; 94% ee; mp 112–113 °C; IR (cmÀ1):
1732, 1703, 1550, 1496, 1433, 1361, 1272, 1140, 702. 1H NMR
(400 MHz, CDCl3): d = 7.26–7.19 (m, 3H), 7.12–7.10 (m, 2H),
4.58–4.55 (m, 2H), 4.30 (d, J = 10.5 Hz, 1H), 4.21–4.17 (m, 1H),
2.23 (s, 3H), 1.87 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): d
201.8, 201.0, 135.9, 129.3, 128.6, 127.9, 78.2, 70.7, 42.7, 30.5,
29.6 ppm. HPLC analysis [Chiralpak AS-H column, hexane–2-
propanol = 85:15, flow rate: 1.0 mL/min, wavelength = 210 nm: tR
White solid; yield 98%; 84% ee; mp 95 °C; IR (cmÀ1): 1732,
1703, 1600, 1554, 1543, 1495, 1437, 1361, 1262, 1141, 1040,
793, 704. 1H NMR (400 MHz, CDCl3): d = 7.24 (s, 1H), 6.82–6.70
(m, 3H), 4.64–4.57 (m, 2H), 4.36 (d, J = 10.8 Hz, 1H), 4.23–4.18
(m, 1H), 3.77 (s, 3H), 2.29 (s, 3H), 1.96 (s, 3H) ppm; 13C NMR
(100 MHz, CDCl3): d = 201.8, 201.0, 160.0, 137.5, 130.4, 119.9,
114.1, 113.6, 78.1, 70.6, 55.2, 42.7, 30.4, 29.6 ppm. HPLC analysis
[Chiralpak AD-H column, hexane–2-propanol = 85:15, flow rate:
1.0 mL/min, wavelength = 210 nm: tR (major) = 9.7 min, tR
(major) = 15.1 min, tR (minor) = 24.1 min]. [
a
]
D
25 = +196.2 (c 1.0,
(minor) = 12.4 min]. [a]
25 = +207.3 (c 0.25, CHCl3).
D
CHCl3).
4.3.7. (S)-3-[1-(4-Methoxyphenyl)-2-nitroethyl]-pentane-2,4-
dione 11g17a
4.3.2. (S)-3-[1-(2-Bromophenyl)-2-nitroethyl]-pentane-2,4-dione
11b17b
White solid; yield 97%; 81% ee; mp 116–118 °C; IR (cmÀ1):
1733, 1705, 1614, 1549, 1515, 1438, 1363, 1261, 1171, 1141,
812. 1H NMR (400 MHz, CDCl3) d = 7.09 (d, J = 8.7 Hz, 2H), 6.83
(d, J = 8.8 Hz, 2H), 4.58–4.55 (m, 2H), 4.32 (d, J = 10.9 Hz, 1H),
4.21–4.15 (m,1H), 3.76 (s, 3H), 2.28 (s, 3H), 1.93 (s, 3H) ppm; 13C
NMR (100 MHz, CDCl3): d = 201.9, 201.2, 159.4, 129.0, 127.6,
114.6, 78.4, 70.8, 55.2, 42.1, 30.4, 29.5 ppm. HPLC analysis [Chiral-
pak AD-H column, hexane–2-propanol = 90:10, flow rate: 1.0 mL/
min, wavelength = 210 nm: tR (major) = 15.4 min, tR (minor)
Orange solid; yield 61%, 89% ee; mp 87 °C; IR (cmÀ1): 1727,
1702, 1553, 1472, 1433, 1359, 1259, 1154, 762. 1H NMR
(400 MHz, CDCl3): d = 7.63 (d, J = 7.9 Hz, 1H), 7.30–7.26 (m, 1H),
7.19–7.12 (m, 2H), 4.85–4.71 (m, 2H), 4.68–4.64 (m, 1H), 4.59 (d,
J = 9.4 Hz, 1H), 2.29 (s, 3H), 2.04 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3): d = 201.9, 200.8, 135.0, 134.0, 129.9, 128.3, 76.2, 69.1,
41.0, 30.9, 28.3 ppm. HPLC analysis [Chiralpak AD-H column,
hexane–2-propanol = 97:3, flow rate: 0.5 mL/min, wave-
length = 210 nm: tR (major) = 21.8 min, tR (minor) = 27.3 min].
= 24.0 min]. [a]
25 = +119.7 (c 2.5, CHCl3).
D
[a]
25 = +209.3 (c 1.0, CHCl3).
D
4.3.8. (S)-3-[1-(2-Fluorophenyl)-2-nitroethyl]-pentane-2,4-dione
11h17b
4.3.3. (S)-3-[1-(3-Bromophenyl)-2-nitroethyl]-pentane-2,4-dione
11c17b
White solid; yield 59%; 48% ee; mp 57–58 °C; IR (cmÀ1): 1730,
1704, 1554, 1494, 1426, 1361, 1267, 1234, 1178, 1144, 767. 1H
NMR (400 MHz, CDCl3): d = 7.32–7.27 (m, 1H), 7.20–7.03 (m, 3H),
4.75–4.60 (m, 2H), 4.49–4.47 (m, 2H), 2.29 (s, 3H), 2.01 (s, 3H)
ppm; 13C NMR (100 MHz, CDCl3): d = 201.3, 200.7, 130.5, 124.9,
116.4, 76.6, 69.0, 37.9, 30.4, 29.2 ppm. HPLC analysis [Chiralpak
AD-H column, hexane–2-propanol = 90:10, flow rate: 1.0 mL/min,
White solid; yield 86%; 77% ee; mp 102–103 °C; IR (cmÀ1):
1727, 1703, 1550, 1477, 1433, 1383, 1367, 1252, 1141, 790, 699.
1H NMR (400 MHz, CDCl3): d = 7.43 (d, J = 8.9 Hz, 1H), 7.35 (s,
1H), 7.26–7.11 (m, 2H), 4.63–4.61 (m, 2H), 4.33 (d, J = 10.6 Hz,
1H), 4.23–4.18 (m, 1H), 2.29 (s, 3H), 2.00 (s, 3H) ppm; 13C NMR
(100 MHz, CDCl3): d = 201.3, 200.4, 138.5, 131.8, 131.0, 130.8,
126.6, 123.3, 77.7, 70.3, 42.3, 30.5, 29.8 ppm. HPLC analysis
[Chiralpak AS-H column, hexane–2-propanol = 85:15, flow rate:
wavelength = 210 nm:
tR
(major) = 10.4 min,
tR
(minor)
= 11.8 min]. [
a]
D
25 = +186.8 (c 0.4, CHCl3).