The Journal of Organic Chemistry
Article
Daicel CHIRALPAK IG, 25 cm × 4.6 mm i.d., mobile phase 5% IPA/
95% heptane, flow rate 1 mL/min, detector UV 210 nm, tR = 4.2 min,
major; 4.7 min, minor.
(1R)-1-(2-Methylphenyl)ethyl 2-Methylpropanoate ((R)-5j). The
title compound was obtained as a colorless oil (28 mg, 30%) by
following the general procedure from 1-(o-tolyl)ethan-1-ol (4j) (55
μL, 0.4 mmol, 1.0 equiv), 4-nitrophenyl isobutyrate (2b) (84 mg, 0.4
stereochemistry was confirmed by comparison of the optical rotation
data with that from the literature.13c
(1R)-1-(5-Fluoro-2-iodophenyl)ethyl 2-Methylpropanoate ((R)-
5n). The title compound was obtained as a colorless oil (85 mg,
63%) by following the general procedure from 1-(5-fluoro-2-
iodophenyl)ethan-1-ol (4n) (106 μL, 0.4 mmol, 1.0 equiv), 4-
̈
nitrophenyl isobutyrate (2b) (84 mg, 0.4 mmol, 1.0 equiv), Backvall
catalyst 1 (12.8 mg, 0.02 mmol, 0.05 equiv), t-BuOK (2.2 mg, 0.02
mmol, 0.05 equiv), HyperBTM catalyst 3 (6.2 mg, 0.02 mmol, 0.05
̈
mmol, 1.0 equiv), Backvall catalyst 1 (12.8 mg, 0.02 mmol, 0.05
equiv), t-BuOK (2.2 mg, 0.02 mmol, 0.05 equiv), HyperBTM catalyst
3 (6.2 mg, 0.02 mmol, 0.05 equiv), and K2CO3 (82 mg, 0.6 mmol, 1.5
1
equiv), and K2CO3 (82 mg, 0.6 mmol, 1.5 equiv). H NMR (300
1
MHz, CDCl3, ppm) δ 7.75 (1H, dd, J = 8.7, 5.6 Hz), 7.11 (1H, dd, J =
9.8, 3.0 Hz), 6.75 (1H, ddd, J = 8.7, 8.0, 3.0 Hz), 5.90 (1H, q, J = 6.6
Hz), 2.61 (1H, hept, J = 7.0 Hz), 1.47 (3H, d, J = 6.6 Hz), 1.20 (3H,
d, J = 7.0 Hz), 1.19 (3H, d, J = 7.0 Hz); 13C{1H} NMR (75 MHz,
CDCl3, ppm) δ176.0, 163.5 (d, J = 247.6 Hz), 147.1 (d, J = 7.0 Hz),
140.8 (d, J = 7.5 Hz), 116.8 (d, J = 22.0 Hz), 113.8 (d, J = 23.5 Hz),
89.6 (d, J = 3.0 Hz), 75.4, 34.1, 21.3, 19.1, 19.0; 19F NMR (376 MHz,
CDCl3, ppm) δ 112.92−113.11 (m); HRMS-APCI (m/z) calcd for
C12H18NO2FI [M + NH4]+ 354.03608, found 354.03626; [α]2D0 +6.1
(c 2.5, CH2Cl2); HPLC/csp assay (77:23 er): Daicel CHIRALPAK
IG, 25 cm × 4.6 mm i.d., mobile phase 0.5% IPA/99.5% heptane, flow
rate 1 mL/min, detector UV 210 nm, tR = 5.4 min, major; 6.2 min,
minor.
equiv). H NMR (300 MHz, CDCl3, ppm) δ 7.44−7.35 (1H, m),
7.28−7.10 (3H, m), 6.07 (1H, q, J = 6.6 Hz), 2.58 (1H, hept, J = 7.0
Hz), 2.39 (3H, s), 1.50 (3H, d, J = 6.6 Hz), 1.22−1.14 (6H, m);
13C{1H} NMR (75 MHz, CDCl3, ppm) δ 176.4, 140.5, 134.8, 130.5,
127.6, 126.4, 125.3, 69.1, 34.3, 21.5, 19.2, 19.1; HRMS-APCI (m/z)
calcd for C13H22NO2 [M + NH4]+ 224.16451, found 224.16451; [α]2D0
+31.7 (c 0.6, CH2Cl2); HPLC/csp assay (94:6 er): Daicel
CHIRALPAK IC, 25 cm × 4.6 mm i.d., mobile phase 10% MTBE/
90% heptane, flow rate 1 mL/min, detector UV 210 nm, tR = 9.8 min,
major; 10.8 min, minor.
(1R)-1-(3-Methylphenyl)ethyl 2-Methylpropanoate ((R)-5k). The
title compound was obtained as a colorless oil (65 mg, 79%) by
following the general procedure from 1-(m-tolyl)ethyl isobutyrate
(4k) (55 μL, 0.4 mmol, 1.0 equiv), 4-nitrophenyl isobutyrate (2b)
(1R)-1-(4-Methoxyphenyl)-2-methylpropyl 2-Methylpropanoate
((R)-5o). The title compound was obtained as a colorless oil (87 mg,
87%) by following the general procedure from 1-(4-methoxyphenyl)-
2-methylpropan-1-ol (4o) (63 μL, 0.4 mmol, 1.0 equiv), 4-
̈
(84 mg, 0.4 mmol, 1.0 equiv), Backvall catalyst 1 (12.8 mg, 0.02
mmol, 0.05 equiv), t-BuOK (2.2 mg, 0.02 mmol, 0.05 equiv),
HyperBTM catalyst 3 (6.2 mg, 0.02 mmol, 0.05 equiv), and K2CO3
1
̈
nitrophenyl isobutyrate (2b) (84 mg, 0.4 mmol, 1.0 equiv), Backvall
(82 mg, 0.6 mmol, 1.5 equiv). H NMR (300 MHz, CDCl3, ppm) δ
catalyst 1 (12.8 mg, 0.02 mmol, 0.05 equiv), t-BuOK (2.2 mg, 0.02
mmol, 0.05 equiv), HyperBTM catalyst 3 (6.2 mg, 0.02 mmol, 0.05
7.34−7.24 (1H, m), 7.23−7.10 (3H, m), 5.89 (1H, q, J = 6.6 Hz),
2.62 (1H, hept, J = 7.0 Hz), 2.40 (3H, s), 1.56 (3H, d, J = 6.6 Hz),
1.26−1.19 (6H, m); 13C{1H} NMR (75 MHz, CDCl3, ppm) δ 176.5,
142.1, 128.6, 128.5, 126.8, 123.1, 72.1, 34.3, 22.5, 21.6, 19.1, 19.0;
HRMS-APCI (m/z) calcd for C13H22NO2 [M + NH4]+ 224.16451,
found 224.16453; [α]2D0 +68.0 (c 1.0, CH2Cl2); HPLC/csp assay
(96:4 er): Daicel CHIRALPAK IC, 25 cm × 4.6 mm i.d., mobile
phase 10% MTBE/90% heptane, flow rate 1 mL/min, detector UV
210 nm, tR = 5.9 min, major; 6.7 min, minor.
(1R)-1-(Naphthalen-1-yl)ethyl 2-Methylpropanoate ((R)-5l). The
title compound was obtained as a white amorphous solid (92 mg,
95%) by following the general procedure from 1-(naphthalen-1-
yl)ethan-1-ol (4l) (69 mg, 0.4 mmol, 1.0 equiv), 4-nitrophenyl
1
equiv), and K2CO3 (82 mg, 0.6 mmol, 1.5 equiv). H NMR (300
MHz, CDCl3, ppm) δ 7.25−7.16 (2H, m), 6.91−6.80 (2H, m), 5.40
(1H, d, J = 7.7 Hz), 3.79 (3H, s), 2.56 (1H, hept, J = 7.0 Hz), 2.18−
1.96 (1H, m), 1.18 (3H, d, J = 7.0 Hz), 1.14 (3H, d, J = 7.0 Hz), 0.97
(3H, d, J = 6.7 Hz), 0.79 (3H, d, J = 6.7 Hz); 13C{1H} NMR (75
MHz, CDCl3, ppm) δ 176.3, 159.1, 132.3, 128.3, 113.6, 80.5, 55.3,
34.4, 33.7, 19.1, 19.0, 18.9, 18.7; HRMS-APCI (m/z) calcd for
C15H26NO3 [M + NH4]+ 268.19072, found 268.19054; [α]2D0 +87.0 (c
1.5, CH2Cl2); HPLC/csp assay (99:1 er): Daicel CHIRALPAK IG, 25
cm × 4.6 mm i.d., mobile phase 5% IPA/95% heptane, flow rate 1
mL/min, detector UV 210 nm, tR = 5.0 min, major; 6.3 min, minor.
(1R)-1-(4-Chlorophenyl)-2-methylpropyl 2-Methylpropanoate
((R)-5p). The title compound was obtained as a colorless oil (83
mg, 81%) by following the general procedure from 1-(4-
chlorophenyl)-2-methylpropan-1-ol (4p) (74 mg, 0.4 mmol, 1.0
equiv), 4-nitrophenyl isobutyrate (2b) (84 mg, 0.4 mmol, 1.0 equiv),
̈
isobutyrate (2b) (84 mg, 0.4 mmol, 1.0 equiv), Backvall catalyst 1
(12.8 mg, 0.02 mmol, 0.05 equiv), t-BuOK (2.2 mg, 0.02 mmol, 0.05
equiv), HyperBTM catalyst 3 (6.2 mg, 0.02 mmol, 0.05 equiv), and
1
K2CO3 (82 mg, 0.6 mmol, 1.5 equiv). H NMR (300 MHz, CDCl3,
ppm) δ 8.14−8.04 (1H, m), 7.91−7.83 (1H, m), 7.83−7.73 (1H, m),
7.66−7.59 (1H, m), 7.58−7.42 (3H, m), 6.65 (1H, q, J = 6.6 Hz),
2.64 (1H, hept, J = 7.0 Hz), 1.71 (3H, d, J = 6.6 Hz), 1.23 (3H, d, J =
7.0 Hz), 1.19 (3H, d, J = 7.0 Hz). The 1H NMR spectrum was
identical to that from the literature.13d [α]D20 +36.3 (c 0.8, CH2Cl2);
HPLC/csp assay (96:4 er): Daicel CHIRALPAK IC, 25 cm × 4.6 mm
i.d., mobile phase 5% IPA/95% heptane, flow rate 1 mL/min, detector
UV 210 nm, tR = 5.2 min, major; 6.9 min, minor. The absolute
stereochemistry was confirmed by comparison of the optical rotation
data with that from the literature.13c
(1R)-1-(Naphthalen-2-yl)ethyl 2-Methylpropanoate ((R)-5m).
The title compound was obtained as a white amorphous solid (93
mg, 96%) by following the general procedure from 1-(naphthalen-2-
yl)ethan-1-ol (4m) (69 mg, 0.4 mmol, 1.0 equiv), 4-nitrophenyl
̈
Backvall catalyst 1 (12.8 mg, 0.02 mmol, 0.05 equiv), t-BuOK (2.2
mg, 0.02 mmol, 0.05 equiv), HyperBTM catalyst 3 (6.2 mg, 0.02
1
mmol, 0.05 equiv), and K2CO3 (82 mg, 0.6 mmol, 1.5 equiv). H
NMR (300 MHz, CDCl3, ppm) δ 7.33−7.27 (2H, m), 7.26−7.16
(2H, m), 5.41 (1H, d, J = 7.4 Hz), 2.58 (1H, hept, J = 7.0 Hz), 2.17−
1.95 (1H, m), 1.19 (3H, d, J = 7.0 Hz), 1.15 (3H, d, J = 7.0 Hz), 0.96
(3H, d, J = 6.8 Hz), 0.80 (3H, d, J = 6.8 Hz); 13C{1H} NMR (75
MHz, CDCl3, ppm) δ 176.3, 138.7, 133.5, 128.5, 128.4, 80.0, 34.3,
33.7, 19.1, 19.0, 18.8, 18.5; HRMS-APCI (m/z) calcd for C14H20O2Cl
[M + H]+ 255.11463, found 255.11446; [α]D20 +90.0 (c 0.27, CHCl3);
HPLC/csp assay (96:4 er): Daicel CHIRALPAK IC, 25 cm × 4.6 mm
i.d., mobile phase 5% IPA/95% heptane, flow rate 1 mL/min, detector
UV 210 nm, tR = 6.6 min, major; 7.3 min, minor.
(1R)-1-(4-Cyanophenyl)ethyl 2-Methylpropanoate ((R)-5q). The
title compound was obtained as a colorless oil (72 mg, 84%) by
following the general procedure from 4-(1-hydroxyethyl)benzonitrile
(4q) (59 mg, 0.4 mmol, 1.0 equiv), 4-nitrophenyl isobutyrate (2b)
̈
isobutyrate (2b) (84 mg, 0.4 mmol, 1.0 equiv), Backvall catalyst 1
(12.8 mg, 0.02 mmol, 0.05 equiv), t-BuOK (2.2 mg, 0.02 mmol, 0.05
equiv), HyperBTM catalyst 3 (6.2 mg, 0.02 mmol, 0.05 equiv), and
1
K2CO3 (82 mg, 0.6 mmol, 1.5 equiv). H NMR (300 MHz, CDCl3,
̈
(84 mg, 0.4 mmol, 1.0 equiv), Backvall catalyst 1 (12.8 mg, 0.02
ppm) δ7.89−7.77 (4H, m), 7.55−7.41 (3H, m), 6.05 (1H, q, J = 6.6
Hz), 2.61 (1H, hept, J = 7.0 Hz), 1.62 (3H, d, J = 6.6 Hz), 1.21 (3H,
d, J = 7.0 Hz), 1.18 (3H, d, J = 7.0 Hz). The 1H NMR spectrum was
identical to that from the literature.13d [α]D20 +100.5 (c 1.9, CH2Cl2);
HPLC/csp assay (97:3 er): Daicel CHIRALPAK IC, 25 cm × 4.6 mm
i.d., mobile phase 5% IPA/95% heptane, flow rate 1 mL/min, detector
UV 210 nm, tR = 5.3 min, major; 6.7 min, minor. The absolute
mmol, 0.05 equiv), t-BuOK (2.2 mg, 0.02 mmol, 0.05 equiv),
HyperBTM catalyst 3 (6.2 mg, 0.02 mmol, 0.05 equiv), and K2CO3
1
(82 mg, 0.6 mmol, 1.5 equiv). H NMR (300 MHz, CDCl3, ppm) δ
7.69−7.59 (2H, m), 7.49−7.38 (2H, m), 5.86 (1H, q, J = 6.6 Hz),
2.59 (1H, hept, J = 7.0 Hz), 1.52 (3H, d, J = 6.6 Hz), 1.22−1.10 (6H,
m); 13C{1H} NMR (75 MHz, CDCl3, ppm) δ 176.2, 147.4, 132.6,
7199
J. Org. Chem. 2021, 86, 7189−7202