The Journal of Organic Chemistry
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reported.39 HPLC (OD-H, 1% i-PrOH/hexane): 54.7 min (S), 58.4
min (R). Propionate ester: H NMR (300 MHz, CDCl3): δ 8.22 (s,
2986, 1758, 1271, 1178, 1086, 730. MS HR-ESI: calcd for
+
C19H15F3NaO2 (M + Na+) 355.0916, found 355.0917.
1
3-Chloro-1-phenylpropan-1-ol (28). Alcohol: Synthesized by
borohydride reduction of the corresponding ketone. H NMR data
1H), 8.14 (d, J = 7.8 Hz, 1H), 7.66 (d, J = 7.5 Hz, 1H), 7.52 (t, J =
7.8 Hz, 1H), 5.93 (q, J = 6.6 Hz, 1H), 2.43−2.34(m, 1H). 13C NMR
(75 MHz, CDCl3): δ 173.8, 148.7, 144.3, 132.5, 129.8, 123.0, 121.2,
71.1, 28.0, 9.2; IR: 2983, 2941, 1739, 1532, 1351, 1182, 1082, 1065,
738, 688. MS HR-ESI: calcd for C11H13NNaO4+ (M + Na+) 246.0737,
found 246.0736.
1
(see the Supporting Information) are in agreement with those
previously reported.42 HPLC (AS-H, 1% i-PrOH/hexane): 22.5 min
1
(R), 26.0 min (S). Propionate ester: H NMR (300 MHz, CDCl3): δ
7.36−7.26 (m, 5H), 5.95 (dd, J1 = 8.4 Hz, J2 = 5.4 Hz, 1H), 3.61−3.41
(m, 2H), 2.45−2.16 (m, 4H), 1.14 (t, J = 7.5 Hz, 3H). 13C NMR (75
MHz, CDCl3): δ 173.6, 139.9, 128.9, 128.4, 126.6, 73.2, 40.9, 39.4,
27.9, 9.3. IR (KBr, cm−1): 3033, 2979, 1740, 1183, 699. MS HR-ESI:
1-[3,5-Bis(trifluoromethyl)phenyl]ethan-1-ol (21). Alcohol: Com-
mercially available. HPLC (OD-H, 2% i-PrOH/hexane): 9.2 min (R);
1
10.4 min (S). Propionate ester: H NMR (300 MHz, CDCl3): δ 7.81
+
calcd for C12H15ClNaO2 (M + Na+) 249.0653, found 249.0652.
(s, 1H), 7.79 (s, 2H), 5.96 (q, J = 6.6 Hz, 1H), 2.41 (q, J = 7.8 Hz,
2H), 1.57 (d, J = 6.6 Hz, 3H), 1.15 (t, J = 7.2 Hz, 3H). 13C NMR (75
MHz, CDCl3): δ 173.6, 144.8, 132.4, 131.9, 126.4, 122.0, 70.9, 27.9,
22.5, 9.2. IR (KBr, cm−1) 2988, 1745, 1280, 1175, 1134, 899, 683; MS
1-Phenyl-2-(pyridin-2-yl)ethan-1-ol (32). Alcohol: Synthesized
from 2-picoline and benzaldehyde as previously described.6g,43 1H
NMR data (see the Supporting Information) are in agreement with
those previously reported.43 HPLC (OD-H, 10% i-PrOH/hexane): 9.0
min (R), 15.4 min (S). Propionate ester: 1H NMR (300 MHz, CDCl3):
δ 8.54 (m, 1H), 7.56 (td, J1 = 7.8 Hz, J2 = 1.8 Hz, 1H), 7.38−7.26 (m,
5H), 7.14−7.09 (m, 2H), 6.20 (dd, J1 = 9.0 Hz, J2 = 5.4 Hz, 1H),
3.41−3.20 (m, 2H), 2.25 (q, J = 7.8 Hz, 2H), 1.02 (t, J = 7.2 Hz, 3H).
13C NMR (75 MHz, CDCl3): δ 173.5, 157.7, 149.6, 140.6, 136.4,
128.7, 128.2, 126.7, 124.1, 121.9, 75.5, 45.6, 27.9, 9.2. IR (KBr, cm−1)
3033, 2980, 2941, 1737, 1182, 763, 700. MS HR-ESI: calcd for
+
HR-ESI: calcd for C13H12F6NaO2 (M + Na+) 337.0633, found
337.0649.
1-(2-Methoxyphenyl)ethan-1-ol (23). Alcohol: Synthesized by
1
borohydride reduction of the corresponding ketone. H NMR data
(see the Supporting Information) are in agreement with those pre-
viously reported.40 (+)-(R) enantiomer37 recovered after KR using
(S)-2 and -3. HPLC (OD-H, 2% i-PrOH/hexane): 18.3 min (S),
19.8 min (R).
+
C16H17NNaO2 (M + Na+) 278.1151, found 278.1152. Isobutyrate
1
Propionate Ester. H NMR (300 MHz, CDCl3): δ 7.36 (dd; J1 =
ester: 1H NMR (300 MHz, CDCl3): δ 8.45 (m, 1H), 7.56 (td, J1 = 7.8
Hz, J2 = 1.8 Hz, 1H), 7.38−7.24 (m, 5H), 7.14−7.10 (m, 2H), 6.19
(dd, J1 = 9.0 Hz, J2 = 5.4 Hz, 1H), 3.40−3.21 (m, 2H), 2.51−2.42
(m, 1H), 1.03 (t, J = 7.2 Hz, 3H), 1.01 (t, J = 7.2 Hz, 3H). 13C NMR
(75 MHz, CDCl3): δ 176.1, 157.7, 149.6, 140.7, 136.4, 128.7, 128.1,
126.6, 124.1, 121.9, 75.4, 45.7, 34.2, 19.1, 18.9. IR (KBr, cm−1): 3033,
2973, 1734, 1190, 1153, 762, 699. MS HR-ESI: calcd for
7.4 Hz, J2 = 1.6 Hz; 1H), 7.26 (td; J1 = 7.4 Hz, J2 = 1.6 Hz; 1H), 6.96
(td; J1 = 7.4 Hz, J2 = 0.8 Hz; 1H), 6.87 (dd; J1 = 7.4 Hz, J2 = 0.8 Hz;
1H), 6.26 (q; J = 6.5 Hz; 1H), 3.84 (s; 3H), 2.37 (q; J = 7.7 Hz; 2H),
1.48 (d; J = 6.5 Hz; 3H), 1.16 (t; J = 7.7 Hz; 3H). 13C NMR (75 MHz,
CDCl3) δ 173.5, 156.0, 130.6, 128.5, 125.7, 120.6, 110.5, 66.9, 55.4,
27.9, 21.2, 9.2. IR (KBr, cm−1): 2981.8, 2940.5, 1737.9, 1187.3. MS
HR-ESI: calcd for C12H16O3Na (M + Na+) m/z 231.0997, found
231.0986;
+
C17H19NNaO2 (M + Na+) 292.1308, found 292.1308.
1-(2,6-Dimethoxyphenyl)ethan-1-ol (25). Previously reported41
without characterization. Synthesized as described below.
tert-Butyl (2R)-2-[(2R)-2-Hydroxy-2-phenylethyl]piperidine-1-
carboxylate (33). Alcohol: Synthesized from 1-phenyl-2-(pyridin-2-
yl)ethan-1-ol 32 (see above) as previously described.6g 1H NMR data
(see the Supporting Information) are in agreement with those
previously reported.44 HPLC (OD-H, 2% i-PrOH/hexane): 12.6 min
1
(R); 26.2 min (S). Propionate ester: H NMR (300 MHz, CDCl3): δ
7.35−7.24 (m, 5H), 5.72 (dd, J1 = 8.4 Hz, J2 = 5.7 Hz, 1H), 4.26 (br,
1H), 3.99 (d, J = 12.6 Hz, 1H), 2.85 (t, J = 12.6 Hz, 1H), 2.41−2.24
(m, 3H), 1.97−1.88 (m, 1H), 1.60−1.49 (m, 5H), 1.43−1.33 (m,
10H), 1.11 (t, J = 7.5 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ 173.9,
155.0, 140.9, 128.7, 128.2, 126.9, 79.5, 74.1, 36.4, 28.7, 28.1, 27.9, 25.7,
19.2, 9.2. IR (KBr, cm−1) 2975, 2935, 1739, 1689, 1164, 699; MS HR-
A solution of 1,3-dimethoxybenzene (786 mg, 5.69 mmol) in 20 mL
of THF was cooled to −78 °C and treated with 1.96 M n-BuLi in
hexanes (3.8 mL, 7.5 mmol). The reaction mixture was allowed to
warm to rt, stirred for 2 h, and then cooled to −78 °C and treated with
acetaldehyde (0.5 mL, 9 mmol). The mixture was allowed to warm to
rt and worked up as usual with water and Et2O. The organic phase was
dried over MgSO4, concentrated, and subjected to flash chromatog-
raphy (15→20% EtOAc/hexanes) to afford a pale-yellow solid (608 mg,
59% yield). Mp: 54−55 °C (from hexanes). 1H NMR (300 MHz,
CDCl3): δ 7.26 (t, J = 8.1 Hz, 1H), 6.56 (d, J = 8.1 Hz, 2H), 5.38−5.27
(m, 1H), 3.88 (br, 1H), 3.84 (s, 3H), 1.49 (d, J = 6.6 Hz, 3H). 13C NMR
(75 MHz, CDCl3) δ 157.4, 128.1, 120.9, 104.3, 64.0, 55.7, 23.6. IR: 2967,
1596, 1477, 1234, 1108. MS HR-ESI: calcd for C10H14O3Na+ (M + Na+)
205.0835, found 205.0844.
+
ESI: calcd for C21H31NNaO4 (M + Na+) 384.2145, found 384.2143.
Isobutyrate ester: 1H NMR (300 MHz, CDCl3): δ 7.34−7.24 (m, 5H),
5.69 (dd, J1 = 8.4 Hz, J2 = 6.0 Hz, 1H), 4.27 (br, 1H), 3.99 (d, J = 12.6
Hz, 1H), 2.85 (t, J = 12.6 Hz, 1H), 2.61−2.51 (m, 1H), 2.32−2.22 (m,
1H), 1.98−1.90 (m, 1H), 1.60−1.49 (m, 5H), 1.43−1.33 (m, 10H),
1.16 (d, J = 7.2 Hz, 3H), 1.13 (d, J = 6.9 Hz, 3H). 13C NMR (75 MHz,
CDCl3): δ 176.4, 155.0, 141.0, 128.7, 128.1, 126.7, 79.5, 74.0, 36.4,
34.3, 28.7, 27.9, 25.7, 19.2, 19.1, 19.0. IR (KBr, cm−1) 2973, 2933,
+
1734, 1689, 1162, 761, 699. MS HR-ESI: calcd for C22H33NNaO4
(M + Na+) 398.2302, found 398.2297.
1-(Anthracen-9-yl)ethan-1-ol (26). Alcohol: Commercially avail-
able. HPLC (OD-H, 10% i-PrOH/hexane): 10.4 min (S), 21.5 min
(R). Propionate ester: 1H NMR (300 MHz, CDCl3): δ 8.63 (d, J = 8.7 Hz,
2H), 8.43 (s, 1H), 8.01 (d, J = 7.8 Hz, 2H), 7.57−7.44 (m, 5H), 2.49−2.29
(m, 2H), 1.95 (d, J = 6.6 Hz, 3H), 1.11 (t, J = 7.5 Hz, 3H). 13C NMR (75
MHz, CDCl3): δ 174.1, 132.6, 131.9, 129.6, 129.6, 128.7, 126.1, 125.0, 69.0,
28.0, 21.8, 9.2. IR: 3052, 2981, 1939, 1736, 1670, 1183, 732, 698. MS HR-
ESI:: calcd for C19H18NaO2+ (M + Na+) 301.1199, found 301.1195.
1-(Anthracen-9-yl)-2,2,2-trifluoroethan-1-ol (27). Alcohol: Com-
mercially available. HPLC (OD-H, 10% i-PrOH/hexane): 12.1 min
tert-Butyl (2S)-2-[(2R)-2-Hydroxy-2-phenylethyl]piperidine-1-car-
boxylate (34). Alcohol: Synthesized from 1-phenyl-2-(pyridin-2-
yl)ethan-1-ol 32 (see above) as previously described.6g 1H NMR
data (see the Supporting Information) are in agreement with those
previously reported.44 HPLC (AD-H, 8% i-PrOH/hexane): 9.4 min
1
(R); 19.9 min (S). Propionate ester: H NMR (300 MHz, CDCl3): δ
7.33−7.24 (m, 5H), 5.58(t, J = 6.9 Hz, 1H), 5.60−3.98 (br, 2H), 2.73
(t, J = 12.6 Hz, 1H), 2.42−2.04 (m, 4H), 1.58−1.41 (m, 16H), 1.01
(t, J = 7.5 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ 173.7, 155.0,
141.3, 128.7, 128.1, 126.6, 79.5, 73.2, 39.1, 36.8, 28.9, 28.6, 27.9, 25.8,
19.3, 9.1. IR (KBr, cm−1) 2977, 2936, 1743, 1689, 1166, 699. MS HR-
1
(S), 29.2 min (R). Propionate ester: H NMR (300 MHz, CDCl3): δ
+
ESI: calcd for C21H31NNaO4 (M + Na+) 384.2145, found 384.2146.
8.79 (d, J = 9.07 Hz, 1H), 8.57 (s, 1H), 8.39 (d, J = 9.3 Hz, 1H), 8.04
(d, J = 8.4 Hz, 2H), 7.89 (q, J = 8.1 Hz, 1H), 7.68−7.51 (m, 4H),
2.63−2.43 (m, 2H), 1.16 (t, J = 7.5 Hz, 3H). 13C NMR (75 MHz,
CDCl3): δ 172.6, 132.0, 131.7, 131.5, 131.3, 131.1, 129.8, 129.5, 127.9,
126.6, 125.2, 122.8, 121.6, 69.0(q, J = 137.7 Hz), 27.5, 9.0; IR: 3055,
1-(Pyridin-2-yl)ethan-1-ol (35). Alcohol: Synthesized by borohy-
1
dride reduction of the corresponding ketone. H NMR data (see the
Supporting Information) are in agreement with those previously
reported.40 (+)-(R)-Enantiomer45 recovered after KR using (S)-2 and
1733
dx.doi.org/10.1021/jo202220x | J. Org. Chem. 2012, 77, 1722−1737