Metal-Dependent Reaction Tuning
FULL PAPER
139.0 ppm; IR (film): n˜ =3365 cmÀ1; elemental analysis calcd (%) for
C13H18O: C 82.06, H 9.53; found: C 81.93, H 9.68.
3.78 (m, 2H), 3.82–3.95 and 4.16–4.31 (two m, 1H), 4.50 and 4.93 ppm
(2ꢁd, 72:28, J=7.2 and 4.2 Hz, 1H); 13C NMR (50 MHz, CDCl3): d=
23.7, 24.0, 25.1, 34.7, 34.9, 36.1, 36.5, 64.4, 65.5, 72.9, 75.9, 79.1, 79.8,
110.1, 110.6, 126.1, 127.0, 127.6, 128.2, 128.5, 139.8, 140.1 ppm; IR (film):
n˜ =3625, 1589 cmÀ1; elemental analysis calcd (%) for C16H22O2 (246.16):
C 78.01, H 9.00; found: C 77.79, H 8.88.
3-Phenylprop-2E-en-1-ol (7l): colourless oil; 1H NMR (200 MHz, CDCl3,
TMS): d=1.76 (broad, 1H), 4.32 (d, J=5.6 Hz, 1H), 6.23 (dt, J=16.0,
5.6 Hz, 1H), 6.61 (d, J=16.0 Hz, 1H), 7.23–7.40 ppm (m, 5H); 13C NMR
(50 MHz, CDCl3, TMS): d=63.6, 126.5, 127.7, 128.6, 131.0, 136.7 ppm;
IR (film): n˜ =3356, 1603, 971 cmÀ1
.
AHCTUNGTERG(NNUN 2R,3R)-3-Benzyloxy-1,2-cyclohexylidenedioxypentane (12): To a stirred
1-Cyclopentyl-3-phenylprop-2E-en-1-ol (7l’): colourless oil; 1H NMR
(200 MHz, CDCl3, TMS): d=1.25–1.88 (m, 8H), 2.00–2.12 (m, 1H), 4.07
(t, J=6.8 Hz, 1H), 6.23 (dd, J=15.8, 6.8 Hz, 1H), 6.57 (d, J=15.8 Hz,
1H), 7.23–7.40 ppm (m, 5H); 13C NMR (50 MHz, CDCl3, TMS): d=25.6,
26.1, 28.9, 29.8, 43.2, 71.7, 125.6, 126.3, 128.1, 128.4, 129.6, 130.4,
136.8 ppm; IR (film): n˜ =3360, 1598, 967 cmÀ1; elemental analysis calcd
(%) for C14H18O: C 83.12, H 8.97; found: C 83.27, H 8.81.
Octadecan-7-ol (7m): colourless oil; 1H NMR (200 MHz, CDCl3, TMS):
d=0.87 (dist. t, J=7.0 Hz, 6H), 1.25 (s, 26H), 1.41–1.50 (m, 4H), 3.52–
3.59 ppm (m, 1H); 13C NMR (50 MHz, CDCl3, TMS): d=13.9, 22.5, 25.5,
29.3, 29.5, 31.8, 37.3, 71.7 ppm; IR (film): n˜ =3595 cmÀ1; elemental analy-
sis calcd (%) for C18H38O: C 79.92, H 14.16; found: C 80.08, H 14.15.
7-Cyclopentyloctadecan-7-ol (7m’): colourless oil; 1H NMR (200 MHz,
CDCl3, TMS): d=0.85 (dist. t, J=6.8 Hz, 6H), 1.25 (brs, 30H), 1.37–1.55
(m, 9H), 1.88–1.94 ppm (m, 1H); 13C NMR (50 MHz, CDCl3, TMS): d=
14.1, 22.7, 23.7, 25.6, 26.1, 29.3, 29.6, 30.0, 30.4, 31.9, 37.7, 47.5, 75.2 ppm;
IR (film): n˜ =3445 cmÀ1; elemental analysis calcd (%) for C23H46O: C
81.58, H 16.79; found: C 81.42, H 13.89.
suspension of pentane-washed NaH (0.864 g, 18.00 mmol, 50% suspen-
sion in oil) in THF (30 mL) was added 11b (3.0 g, 15.00 mmol) in THF
(20 mL) at room temperature over a period of 30 min. After reflux of the
mixture for 1 h, BnBr (3.70 g, 21.64 mol) in THF (20 mL) was added, and
the mixture was heated at reflux for an additional 1 h, then brought to
room temperature. The mixture was poured into ice-cold water, the or-
ganic layer was separated, and the aqueous portion was extracted with di-
ethyl ether. The combined organic extracts were washed with water and
brine and dried. Solvent removal in vacuo gave a residue, which was puri-
fied by column chromatography (silica gel, 0–10% EtOAc/hexane) to
afford 12 (3.74 g, 86%): colourless oil; [a]2D2 =+29.52 (c=1.03, CHCl3);
1H NMR (200 MHz, CDCl3, TMS): d=0.95 (t, J=6.8 Hz, 3H), 1.26–1.48
(m, 4H), 1.53–1.76 (m, 8H), 3.27–3.40 (m, 1H), 3.56–3.69 (m, 1H), 3.82–
3.98 (m, 1H), 4.15–4.22 (m, 1H), 4.56–4.85 (m, 2H), 7.17–7.40 ppm (m,
5H); 13C NMR (50 MHz, CDCl3): d=9.3, 23.9, 24.0, 25.2, 35.0, 36.3, 66.1,
72.6, 77.7, 80.3, 109.5, 127.6, 127.8, 128.3, 138.7 ppm; IR (film): n˜ =3088,
1102 cmÀ1; elemental analysis calcd (%) for C18H26O3 (290.19): C 74.45,
H 9.02; found: C 74.63, H 8.86.
AHCTUNGRETG(NNUN 2R,3R)-3-Benzyloxypentan-1,2-diol (13): A mixture of 13 (3.70 g,
2-Methylcyclohexanol (9a): colourless oil; 1H NMR (200 MHz, CDCl3,
TMS): d=0.92 (d, J=6.8 Hz, 3H), 0.99 (d, J=6.4 Hz, 3H), 1.19–1.41 (m,
4H), 1.58–1.70 (m, 5H), 1.93 (brs, 1H), 3.06–3.11 and 3.73–3.80 ppm (2ꢁ
m, 1H); 13C NMR (50 MHz, CDCl3, TMS): d=16.8, 18.5, 20.6, 24.4, 25.1,
25.6, 28.7, 32.4, 33.6, 35.4, 35.8, 40.2, 71.1, 76.4 ppm; IR (film): n˜ =
12.76 mmol) and CuCl2·H2O (20 mol%) in MeOH (30 mL) was stirred at
approximately 508C until 12 disappeared (as monitored by TLC, ca. 4 h).
The mixture was concentrated in vacuo, treated with water (25 mL) and
extracted with EtOAc (3ꢁ25 mL). The combined organic extracts were
washed with water (2ꢁ10 mL) and brine (1ꢁ5 mL), dried and concen-
trated in vacuo. The residue was subjected to column chromatography
(silica gel, 0–5% MeOH/CHCl3) to obtain pure 13 (2.46 g, 92%): colour-
less oil; [a]2D2 =+29.12 (c=1.36, CHCl3); 1H NMR (200 MHz, CDCl3,
TMS): d=0.95 (t, J=6.8 Hz, 3H), 1.49–1.68 (m, 2H), 1.71–1.94 (brs,
2H), 3.42–3.52 (m, 1H), 3.67–3.80 (m, 3H), 4.58 (q, J=11.6 Hz, 2H),
7.33 ppm (m, 5H); 13C NMR (50 MHz, CDCl3): d=10.2, 21.6, 65.6, 70.9,
3431 cmÀ1
.
3-Methylcyclohexanol (9b): colourless oil; 1H NMR (200 MHz, CDCl3,
TMS): d=0.88 (d, J=7.2 Hz, 3H), 1.10–1.41 (m, 4H), 1.54–1.71 (m, 3H),
1.89–1.94 (m, 2H), 3.54 ppm (m, 1H); 13C NMR (50 MHz, CDCl3, TMS):
d=22.2, 24.1, 31.3, 33.9, 35.1, 44.4, 70.4 ppm; IR (film): n˜ =3356 cmÀ1
.
4-Methylcyclohexanol (9c): colourless oil; 1H NMR (200 MHz, CDCl3,
TMS): d=0.89 (d, J=6.4 Hz, 3H), 1.13–1.40 (m, 4H), 1.64–1.71 (m, 3H),
1.87–1.93 (m, 2H), 3.51 ppm (m, 1H); 13C NMR (50 MHz, CDCl3, TMS):
75.7, 81.2, 127.6, 128.0, 128.3, 138.9 ppm; IR (film): n˜ =3406, 1067 cmÀ1
;
elemental analysis calcd (%) for C12H18O3 (210.13): C 68.54, H 8.63;
found: C 68.48, H 8.48.
d=21.8, 31.7, 33.3, 35.5, 70.8 ppm; IR (film): n˜ =3349 cmÀ1
.
1
4-tert-Butylcyclohexanol (9d): colourless oil; H NMR (200 MHz, CDCl3,
TMS): d=0.82 (s, 9H), 0.87–1.22 (m, 5H), 1.73–1.78 (m, 2H), 1.95–2.01
(m, 2H), 2.19 (brs, 1H), 3.49 ppm (m, 1H); 13C NMR (50 MHz, CDCl3,
(2R,3R)-3-Benzyloxy1-1,2-epoxypentane (14): To a cooled (À58C) and
stirred solution of 13 (2.4 g, 11.43 mmol) and pyridine (1.1 mL,
13.71 mmol) in CH2Cl2 (20 mL) was added p-toluenesulfonyl chloride
(TsCl, 2.18 g, 11.43 mmol). The mixture was stirred at À58C for 3.5 h and
at 08C overnight, then poured into water and extracted with CHCl3. The
organic extract was washed with water and brine, dried and concentrated
in vacuo. The crude product was purified by column chromatography
(silica gel, 0–10% EtOAc/hexane) to afford the pure monotosylate
(3.72 g, 89%): colourless oil; [a]2D2 =+2.64 (c=1.06, CHCl3); 1H NMR
(200 MHz, CDCl3, TMS): d=0.85 (t, J=6.4 Hz, 3H), 1.47–1.74 (m, 2H),
1.80 (broad, 1H), 2.41 (s, 3H), 3.39–3.51 (m, 1H), 3.72–3.85 (m, 2H),
3.98–4.12 (m, 1H), 4.15–4.22 (m, 1H), 4.36–4.68 (m, 1H), 7.24–7.32 (m,
7H), 7.78 ppm (d, J=8.2 Hz, 2H); 13C NMR (50 MHz, CDCl3): d=9.8,
21.6, 22.6, 69.6, 70.9, 72.3, 79.4, 127.9, 128.4, 129.8, 129.9, 132.6, 138.0,
TMS): d=25.5, 27.5, 32.1, 35.7, 47.0, 70.8 ppm; IR (film): n˜ =3413 cmÀ1
.
5a-Cholestan-3-ol (9e): white solid; m.p. 1408C (lit.[10b] 141–1478C);
1H NMR (200 MHz, CDCl3, TMS): d=0.63 (s, 3H), 0.85 (d, J=6.8 Hz,
3H), 0.93 (d, J=6.8 Hz, 6H), 1.07–1.45 (m containing a s at d 1.42, 24H),
1.50–1.92 (m, 10H), 2.26 (s, 1H), 3.42–3.63 ppm (m, 1H); 13C NMR
(50 MHz, CDCl3, TMS): d=11.8, 12.0, 18.4, 20.9, 22.3, 22.5, 23.6, 23.9,
27.7, 27.9, 28.4, 29.4, 31.1, 31.8, 35.2, 35.5, 35.9, 36.7, 37.8, 39.2, 39.7, 42.3,
44.6, 54.1, 55.9, 56.2, 71.0 ppm; IR (film): n˜ =3607 cmÀ1
.
Isoborneol/borneol (9 f): white solid; m.p. 1958C; 1H NMR (200 MHz,
CDCl3, TMS): d=0.80 and 0.84 (2ꢁs, 3H), 0.88 (s, 3H), 0.92 (s, 3H),
1.28–1.39 (m, 3H), 1.60–1.76 (m, 2H), 1.86 (s, 1H), 2.03–2.08 (m, 1H),
2.27–2.36 (m, 1H), 3.43–3.61 (isoborneol) and 3.95–3.97 ppm (borneol)
(two m, 1H); 13C NMR (50 MHz, CDCl3, TMS): d=11.3, 13.3, 18.6, 20.0,
20.4, 25.8, 27.2, 28.2, 29.6, 33.8, 38.9, 40.3, 45.0, 46.3, 48.9, 49.4, 77.3,
145.0 ppm; IR (film): n˜ =3454, 1599, 1372, 1178 cmÀ1
.
To a stirred suspension of anhydrous K2CO3 (2.11 g, 15.29 mmol) in
MeOH (30 mL) was added the above tosylate (3.72 g, 10.22 mmol). The
mixture was stirred for 2 h and then filtered. The residue was washed
with diethyl ether (2ꢁ10 mL), and the combined filtrates were concen-
trated in vacuo. The residue was taken up in Et2O (40 mL) and washed
with water and brine, dried and concentrated in vacuo to obtain the
crude product, which was purified by column chromatography (silica gel,
0–5% Et2O/hexane) to furnish 14 (1.64 g, 75% from 13): colourless oil;
[a]2D2 =+12.04 (c=1.16, CHCl3); 1H NMR (200 MHz, CDCl3, TMS): d=
0.97 (t, J=7.2 Hz, 3H), 1.54–1.73 (m, 2H), 2.72–2.77 (m, 2H), 2.80–2.94
(m, 1H), 3.15–3.23 (m, 1H), 4.62 (q, J=12.0 Hz, 2H), 7.32 ppm (m, 5H);
13C NMR (50 MHz, CDCl3): d=10.2, 21.8, 41.7, 57.7, 65.4, 80.4, 127.6,
79.8 ppm; IR (film): n˜ =3466 cmÀ1
.
Flavan-4-ol (9g): white solid; m.p. 1028C (lit.[11g] 998C); 1H NMR
(300 MHz, CDCl3, TMS): d=1.67 (s, 1H), 2.15–2.23 (m, 1H), 2.51- 2.62
(m, 1H), 5.08–5.16 (m, 1H), 5.20 (dd, J=11.4, 1.4 Hz, 1H), 6.88–7.03 (m,
2H), 7.18–7.25 (m, 1H), 7.35–7.53 ppm (m, 6H); 13C NMR (50 MHz,
CDCl3, TMS): d=39.9, 65.7, 77.1, 116.7, 121.0, 125.7, 126.1, 127.0, 128.2,
128.7, 129.1, 140.5, 154.5 ppm; IR (film): n˜ =3299 cmÀ1
.
ACHTUNGTRENNUNG(1S/R,2R)-2,3-Cyclohexylidenedioxy-1-phenylpropan-1-ol (10h/11h): col-
1
ourless oil; [a]2D2 =+11.00 (c=0.604, CHCl3); H NMR (200 MHz, CDCl3,
TMS): d=1.22–1.30 (m, 4H), 1.52–1.69 (m, 6H), 2.06 (brs, 1H), 3.67–
Chem. Eur. J. 2009, 15, 1713 – 1722
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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