Diastereoselective Synthesis of syn- and cis-1,2-Diols
syn- and anti-1,2-Diphenyl-2-[(2,2,6,6-tetramethylpiperidin-1-yl)- 1.71 (dquint, J = 3.3, 13.4 Hz, 1 H), 1.86 (s, 1 H), 1.87–1.94 (m, 1
oxy]ethanols (7j): Yield, Method A: 49 mg (70%) as an inseparable
23:1 syn/anti mixture; Method B2: 63 mg (89%) as an inseparable
1:3 syn/anti mixture as a colorless solid. Rf = 0.3 (hexane/EtOAc,
H), 3.61 (ddd, J = 2.5, 4.5, 12.0 Hz, 1 H), 3.99 (t, J = 3.0 Hz, 1
H) ppm. 13C NMR (100 MHz): δ = 17.4 (t), 18.4 (q), 20.4 (q), 24.4
(t), 25.9 (t), 27.9 (t), 34.4 (q), 36.1 (d), 40.7 (t), 60.1 (s), 72.3 (d),
84.7 (d) ppm.
10:1). IR (film): ν = 3600, 2981, 1456, 1382, 1366, 1262, 1244, 1186,
˜
1136, 1066, 1030, 990, 960, 921, 882, 837, 765, 734, 654 cm–1. MS
(1S*,2R*,6R*)-6-Methyl-2-[(2,2,6,6-tetramethylpiperidin-1-yl)-
oxy]cyclohexanol [(1S*,2R*,6R*)-7l]: Yield, Method A: 52 mg
(+ESI): m/z (%) = 354 (100). HRMS (+ESI): m/z calcd. for
+
C23H32NO2 354.2428; found 354.2427.
(97%); colorless oil; R = 0.4 (hexane/EtOAc, 10:1). IR (film): ν =
˜
f
1
Compound syn-7j: M.p. 117 °C. H NMR (400 MHz): δ = 1.17 (s,
3610, 3508, 2940, 2881, 1428, 1379, 1365, 1261, 1235, 1212, 1182,
3 H), 1.26 (s, 3 H), 1.36–1.45 (m, 2 H), 1.50 (s, 3 H), 1.55–1.70 (m, 1136, 1101, 976, 937, 848, 801, 667 cm–1. MS (+ESI): m/z (%) =
+
4 H), 1.71 (s, 3 H), 4.99 (d, J = 8.9 Hz, 1 H), 5.18 (d, J = 8.9 Hz,
270 (100). HRMS (+ESI): m/z calcd. for C16H32NO2 270.2428;
1
1 H), 6.94–7.00 (m, 4 H), 7.06–7.11 (m, 3 H), 7.12–7.17 (m, 3 H),
found 270.2428. H NMR (400 MHz): δ = 0.96 (d, J = 7.2 Hz, 3
8.22 (s, 1 H) ppm. 13C NMR (100 MHz): δ = 17.4 (t), 20.7 (q), 21.0 H), 1.05–1.13 (m, 1 H), 1.17 (s, 12 H), 1.33–1.44 (m, 2 H), 1.44–
(q), 32.4 (q), 34.8 (q), 40.6 (t), 61.0 (s), 62.2 (s), 81.0 (d), 88.8 (d),
127.4 (d), 127.69 (d), 127.74 (d), 127.9 (d), 128.0 (d), 128.2 (d),
138.3 (s), 140.9 (s) ppm.
1.51 (m, 4 H), 1.51–1.60 (m, 2 H), 1.70–1.84 (m, 3 H), 1.92–2.00
(m, 1 H), 2.26 (s, 1 H), 3.68 (dd, J = 3.0, 5.1 Hz, 1 H), 3.91–3.97
(m, 1 H) ppm. 13C NMR (100 MHz): δ = 17.1 (q), 17.3 (t), 20.1
(t), 20.5 (q), 27.6 (t), 28.1 (t), 34.4 (q), 34.7 (d), 40.8 (t), 60.1 (s),
75.0 (d), 80.4 (d) ppm.
1
Compound anti-7j: H NMR (400 MHz): δ = 0.72 (s, 3 H), 1.05 (s,
3 H), 1.21 (s, 3 H), 1.42 (m, 1 H), 1.43 (s, 3 H), 1.45–1.61 (m, 5
H), 2.40 (d, J = 2.5 Hz, 1 H), 4.84 (d, J = 3.6 Hz, 1 H), 5.57 (br.
(2R,3R,6R)-6-Isopropyl-3-methyl-2-[(2,2,6,6-tetramethylpiperidin-1-
dd, J = 3.1, 3.5 Hz, 1 H), 6.89–6.93 (m, 2 H), 6.99–7.03 (m, 2 H), yl)oxy]cyclohexan-1-one [(2R,3R,6R)-6m]: Yield, Method A: 67 mg
7.12–7.17 (m, 6 H) ppm. 13C NMR (100 MHz): δ = 17.3 (t), 20.7 (72 %); colorless solid; m.p. 113 °C; Rf = 0.85 (hexane/EtOAc,
(q), 20.9 (q), 32.5 (q), 34.8 (q), 40.8 (t), 60.6 (s), 62.1 (s), 74.6 (d), 10:1). IR (film): ν = 2943, 2878, 1715, 1473, 1385, 1363, 1263, 1236,
˜
91.0 (d), 126.5 (d), 127.2 (d), 127.3 (d), 127.9 (d), 128.9 (d), 137.4
(s), 140.7 (s) ppm. One p-Ph signal of anti-7j is not distinguishable
in the spectra of the 3:1 anti/syn mixture.
1212, 1176, 1135, 1088, 1032, 1020, 989, 962, 949, 928, 882, 831,
731, 719, 669 cm–1. MS (+ESI): m/z (%) = 332 (100), 310 (38).
+
HRMS (+ESI): m/z calcd. for C19H36NO2 310.2741; found
310.2741. 1H NMR (400 MHz): δ = 0.83 (d, J = 7.1 Hz, 3 H), 0.87
(d, J = 6.7 Hz, 3 H), 0.88 (d, J = 6.7 Hz, 3 H), 0.97 (s, 3 H), 1.14
(s, 3 H), 1.15 (s, 3 H), 1.27 (s, 3 H), 1.28–1.34 (m, 1 H), 1.36–1.48
(m, 4 H), 1.48–1.64 (m, 2 H), 1.64–1.72 (m, 1 H), 1.82–1.94 (m, 2
H), 1.98 (dtd, J = 1.1, 6.6, 12.8 Hz, 1 H), 2.04 (oct, J = 6.6 Hz, 1
H), 2.85–2.92 (m, 1 H), 4.51 (dd, J = 1.1, 5.7 Hz, 1 H) ppm. 13C
NMR (100 MHz): δ = 12.0 (q), 17.3 (t), 20.2 (q), 20.7 (q), 21.7 (q),
26.0 (t), 26.1 (d), 30.4 (t), 32.6 (q), 34.7 (q), 38.0 (d), 40.6 (t), 40.7
(t), 57.7 (d), 59.2 (s), 61.0 (s), 93.5 (d), 210.7 (s) ppm.
(1R*,2S*,4S*)-4-tert-Butyl-2-[(2,2,6,6-tetramethylpiperidin-1-yl)-
oxy]cyclohexanol [(1R*,2S*,4S*)-7k]: Yield, Method A: 41 mg
(66%); colorless solid; m.p. 71 °C; Rf = 0.3 (hexane/EtOAc, 10:1).
IR (film): ν = 3605, 3500, 2943, 2879, 1378, 1367, 1263, 1242, 1214,
˜
1185, 1135, 1107, 1047, 1002, 993, 959, 948, 936, 883, 850, 791,
721, 680 cm–1. MS (+ESI): m/z (%) = 312 (100). HRMS (+ESI):
m/z calcd. for C19H38NO2 312.2897; found 312.2897. 1H NMR
+
(400 MHz): δ = 0.88 (s, 9 H), 0.94–1.01 (m, 1 H), 1.15 (br. s, 12
H), 1.27–1.36 (m, 4 H), 1.38–1.42 (m, 1 H), 1.43–1.57 (m, 5 H),
1.92–2.02 (m, 2 H), 2.01 (s, 1 H), 3.63 (ddd, J = 12.2, 4.3, 2.7 Hz, (1S,2R,3R,6S)-6-Isopropyl-3-methyl-2-[(2,2,6,6-tetramethylpiper-
1 H), 4.17–4.20 (m, 1 H) ppm. 13C NMR (126 MHz, 0 °C): δ = idin-1-yl)oxy]cyclohexan-1-ol [(1S,2R,3R,6S)-7m] and
17.2 (t), 20.2 (t), 20.3 (q), 20.6 (q), 27.1 (t), 27.8 (q), 30.6 (t), 32.7
(s), 34.2 (q), 40.4 (t), 47.0 (d), 59.8 (s), 60.3 (s), 67.2 (d), 84.8
(d) ppm.
(1R,2S,3R,6S)-6-Isopropyl-3-methyl-2-[(2,2,6,6-tetramethylpiper-
idin-1-yl)oxy]cyclohexan-1-ol [(1R,2S,3R,6S)-7m]: Yield, Method
B2: 86 mg (92%) of (1S,2R,3R,6S)-7m starting from (2R,3R,6S)-
6m and 77 mg (82 %) as a separable 1.1:1 (1R,2S,3R,6S)-7m/
(1S,2R,3R,6S)-7m mixture starting from a 1.1:1 mixture of the cor-
responding 6m isomers.
(1S*,2R*,4S*)-4-tert-Butyl-2-[(2,2,6,6-tetramethylpiperidin-1-yl)-
oxy]cyclohexanol [(1S*,2R*,4S*)-7k]: Yield, Method A: 45 mg
(73%); colorless oil; R = 0.3 (hexane/EtOAc, 10:1). IR (film): ν =
˜
f
3601, 3467, 2939, 2878, 1473, 1380, 1367, 1259, 1245, 1212, 1185,
Compound (1S,2R,3R,6S)-7m: Pale-yellow oil; Rf = 0.6 (hexane/
1136, 1109, 1066, 1017, 984, 926, 823, 709 cm–1. MS (+ESI): m/z
EtOAc, 10:1). IR (film): ν = 3294, 2937, 2879, 1465, 1371, 1261,
˜
+
(%) = 312 (100). HRMS (+ESI): m/z calcd. for C19H38NO2
1241, 1178, 1135, 1111, 1064, 1050, 1029, 964, 926, 902, 886, 848,
1
312.2897; found 312.2897. H NMR (400 MHz): δ = 0.84 (s, 9 H), 791, 720, 689 cm–1. MS (+ESI): m/z (%) = 312 (100). HRMS
+
1
0.96–1.04 (m, 2 H), 1.24 (br. s, 12 H), 1.38–1.47 (m, 2 H), 1.45–
1.54 (m, 5 H), 1.52–1.60 (m, 1 H), 1.70–1.84 (m, 2 H), 2.27 (ddd,
J = 2.9, 11.6, 15.3 Hz, 1 H), 2.66 (s, 1 H), 3.52 (dt, J = 4.0, 12.2 Hz,
1 H), 4.35 (dt, J = 3.0, 3.2 Hz, 1 H) ppm. 13C NMR (126 MHz,
0 °C): δ = 17.1 (t), 20.6 (q), 20.7 (q), 25.5 (t), 27.6 (q), 30.0 (t), 31.3
(t), 32.7 (s), 34.5 (q), 35.2 (q), 40.5 (d), 40.8 (t), 41.3 (t), 59.6 (br.
s), 61.2 (br. s), 73.2 (d), 80.5 (d) ppm.
(+ESI): m/z calcd. for C19H38NO2 312.2897; found 312.2897. H
NMR (400 MHz): δ = 0.79 (d, J = 6.9 Hz, 3 H), 0.83–0.95 (m, 1
H), 0.91 (d, J = 7.1 Hz, 3 H), 1.10 (d, J = 7.0 Hz, 3 H), 1.15 (s, 3
H), 1.24 (s, 3 H), 1.27–1.34 (m, 3 H), 1.38 (s, 3 H), 1.40–1.50 (m,
2 H), 1.44 (s, 3 H), 1.50–1.62 (m, 5 H), 2.04 (tt, J = 3.7, 11.0 Hz,
1 H), 2.17 (dsept, J = 3.7, 6.9 Hz, 1 H), 3.55 (dd, J = 3.2, 11.0 Hz,
1 H), 4.64 (t, J = 3.3 Hz, 1 H), 6.23 (s, 1 H) ppm. 13C NMR
(100 MHz): δ = 16.4 (q), 17.2 (t), 18.5 (q), 20.6 (q), 20.8 (q), 21.3
(q), 23.3 (t), 25.7 (d), 28.4 (t), 35.4 (q), 36.6 (d), 36.7 (q), 40.8 (t),
41.9 (t), 43.2 (d), 61.2 (s), 62.4 (s), 77.2 (d), 79.4 (d) ppm.
(1R*,2S*,6R*)-6-Methyl-2-[(2,2,6,6-tetramethylpiperidin-1-yl)-
oxy]cyclohexanol [(1R*,2S*,6R*)-7l]: Yield, Method A: 40 mg
(74%); colorless solid; m.p. 38 °C; Rf = 0.6 (hexane/EtOAc, 10:1).
IR (film): ν = 3597, 3508, 2938, 2879, 1461, 1379, 1365, 1261, 1236,
Compound (1R,2S,3R,6S)-7m: Pale-yellow oil; Rf = 0.8 (hexane/
˜
1212, 1186, 1135, 1084, 1058, 1047, 1014, 990, 961, 949, 913, 883,
EtOAc, 10:1). IR (film): ν = 3607, 2936, 2879, 1468, 1380, 1367,
˜
836, 795, 719, 664 cm–1. MS (+ESI): m/z (%) = 270 (100). HRMS
1261, 1244, 1180, 1136, 1087, 1064, 1021, 980, 946, 916, 879, 855,
+
1
(+ESI): m/z calcd. for C16H32NO2 270.2428; found 270.2428. H
NMR (400 MHz): δ = 1.02 (d, J = 6.8 Hz, 3 H), 1.05–1.22 (m, 13
H), 1.33–1.44 (m, 2 H), 1.40–1.52 (m, 7 H), 1.49–1.60 (m, 1 H),
809, 693 cm–1. MS (+ESI): m/z (%) = 334 (10), 312 (100). HRMS
+
1
(+ESI): m/z calcd. for C19H38NO2 312.2897; found 312.2898. H
NMR (400 MHz): δ = 0.84–0.90 (m, 1 H), 0.91 (d, J = 6.7 Hz, 3
Eur. J. Org. Chem. 2015, 7785–7798
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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