pure spirocyclic diol ligands can be readily obtained, if the
established chiral resolution procedures are put in use.12,14
In conclusion, we have developed a facile and efficient
method for the construction of chiral quaternary carbon
through the ZnBr2-catalyzed semipinacol rearrangement of
α-hydroxy epoxides. This method is expected to find more
applications in organic synthesis.
δH 0.84 (d, J 6.6, 3H), 0.90 (d, J 6.6, 3H), 1.03 (s, 3H), 1.04
(s, 3H), 1.05–2.08 (m, 12H), 2.45–2.46 (m, 1H), 2.67–2.75 (m,
1H), 3.73 (d, J 7.6, 1H), 3.93 (br s, 1H); δC 19.6, 21.7, 22.2, 22.7,
24.0, 25.1, 25.5, 27.6, 28.1, 29.4, 32.3, 36.9, 40.1, 40.3, 51.0,
52.1, 71.4, 74.2, 215.7, 215.7; m/z (GC-MS) 4b: 170 (Mϩ, 5%),
152 (5), 109 (68), 95 (49), 85 (97), 68 (51), 43 (100); 4c: 170
(Mϩ, 10%), 152 (2), 123 (11), 109 (13), 84 (52), 68 (88), 43 (100);
HRMS (EI): found 170.1326; calc. for C10H18O2: 170.1307.
Experimental
2-Acetyl-2-phenylcyclohexan-1-ol 5b. Following the typical
procedure above (rt, 1 h), the epoxide 5a (200 mg, 0.92 mmol)
was treated with ZnBr2 (6.2 mg, 0.028 mmol) to afford the
product 5b (188 mg) in 94% yield. δH 1.31–1.70 (m, 6H), 1.86
(s, 3H), 2.15–2.19 (m, 2H), 3.22 (br, 1H), 4.20 (br s, 1H), 7.18–
7.29 (m, 5H); δC 21.4, 21.9, 26.1, 28.2, 29.9, 60.2, 72.7, 127.2,
127.5, 127.5, 128.8, 128.8, 138.8, 212.9; m/z (GC-MS) 218 (Mϩ,
4%), 175 (18), 158 (72), 147 (24), 143 (25), 129 (35), 115 (22), 91
(100), 77 (25); HRMS (EI): found 218.1291; calc. for C14H18O2:
218.1307.
1
The H NMR and 13C NMR data in CDCl3 solution were
recorded on a Bruker AM-400 MHz spectrometer. The
chemical shifts are reported in ppm relative to TMS. J Values
are given in Hz. The GC-MS, MS and HRMS data were
obtained with EI (70 eV). Column chromatographies were
generally performed on silica gel (200–300 meshes) eluting
with petroleum ether–EtOAc (20:1→50:1). Unless otherwise
noted, TLC inspections on silica gel F254 plates were performed
with petroleum ether–EtOAc (10:2.5). All starting α-hydroxy
epoxides were prepared by literature procedures12 and were
characterized by NMR and mass spectroscopy.
2-Propionyl-2-phenylcyclohexan-1-ol 6b. Following the
typical procedure above (rt, 0.5 h), the epoxide 6a (200 mg, 0.86
mmol) was treated with ZnBr2 (5.8 mg, 0.026 mmol) to afford
the product 6b (178 mg) in 89% yield. δH 0.80 (t, J 7, 3H),
1.29–1.69 (m, 6H), 2.15–2.20 (m, 4H), 3.33 (br, 1H), 4.20 (br s,
1H), 7.15–7.29 (m, 5H); δC 8.0, 21.4, 21.9, 28.0, 29.9, 30.9,
60.0, 72.8, 127.0, 127.4, 127.4, 128.6, 128.6, 139.1, 215.6; m/z
(GC-MS) 232 (Mϩ, 2%), 175 (10), 158 (100), 130 (42), 91
(84), 77 (27), 57 (37); HRMS (EI): 232.1442; calc. for C15H20O2:
232.1463.
General procedure for rearrangement reaction
To a solution of α-hydroxy epoxide (~1 mmol) in dry CH2Cl2
(~10 ml) was added ZnBr2 (2–8 mol%) under argon. The
mixture was stirred at rt and monitored with TLC until the
starting material disappeared. The reaction mixture was
partitioned with water, the organic phase dried over MgSO4
and concentrated in vacuo. The residue was purified by column
chromatography on silica gel to give the β-hydroxy ketone.
2-(2Ј-Methylpropionyl)-2-phenylcyclohexan-1-ol 7b. Follow-
ing the typical procedure above (rt, 4 h), the epoxide 7a (200
mg, 0.81 mmol) was treated with ZnBr2 (5.5 mg, 0.024 mmol) to
afford the product 7b (190 mg) in 95% yield. δH 0.61 (d, J 6.6,
3H), 0.92 (d, J 6.7, 3H), 1.36–1.40 (m, 2H), 1.64–1.76 (m, 5H),
2.25 (m, 1H), 2.37 (m, 1H), 2.73 (m, 1H), 4.54 (br s, 1H), 7.25–
7.42 (m, 5H); δC 20.2, 20.4, 20.9, 21.6, 25.6, 28.8, 35.5, 60.4,
71.4, 127.2, 128.3, 128.3, 128.7, 128.7, 137.6, 219.4; m/z (GC-
MS) 246 (Mϩ, <1%), 158 (100), 143 (36), 130 (39), 115 (16), 105
(14), 91 (57), 77 (19); HRMS (EI): found 246.1678; calc. for
C16H22O2: 246.1620.
1-Hydroxyspiro[5,5]undecan-7-one 1b. Following the typical
procedure above (rt, 8 h), the epoxide 1a (200 mg, 1.10 mmol)
was treated with ZnBr2 (9.9 mg, 0.044 mmol) to afford the
product 1b (182 mg) in 91% yield. δH 1.19 (m, 1H), 1.25–1.37
(m, 2H), 1.47 (m, 1H), 1.61–1.83 (m, 7H), 1.92–1.98 (m, 2H),
2.16–2.21 (m, 2H), 2.52 (m, 1H), 3.22 (br, 1H), 3.39 (br s, 1H);
δC 20.2, 21.1, 22.4, 28.1, 29.9, 30.8, 36.0, 39.3, 53.5, 74.1, 219.0;
m/z (GC-MS) 182 (Mϩ, 14%), 164 (41), 135 (18), 111 (100), 98
(44), 81 (32), 67 (33), 55 (48); HRMS (EI): found 182.1307; calc.
for C11H18O2: 182.1306.
1-Hydroxyspiro[5,6]dodecan-7-one 2b/c. Following the
typical procedure above (rt, 14 h), the epoxide 2a (200 mg,
1.02 mmol) was treated with ZnBr2 (11.5 mg, 0.05 mmol) to
afford the product 2b/c (82 mg, 77:23) in 41% total yield.
δH 1.14–2.61 (m, 16H), 3.59 (t, J 4.9, 1H), 3.92 (dd, J 4.1, 11.3,
1H); δC 20.5, 21.5, 21.5, 24.1, 24.7, 25.5, 26.4, 26.5, 27.3, 29.4,
30.1, 30.1, 30.2, 30.7, 33.0, 34.6, 39.9, 41.2, 55.0, 55.6, 73.2,
74.6, 219.0, 219.4; m/z (GC-MS) 2b: 196 (Mϩ, 7%), 178 (15),
149 (11), 125 (89), 111 (53), 81 (72), 67 (52), 55 (100); 2c: 196
(Mϩ, 8%), 178 (22), 149 (15), 125 (87), 111 (59), 81 (44), 67 (47),
55 (100); HRMS (EI): found 196.1469; calc. for C12H20O2:
196.1463.
2-Benzoyl-2-phenylcyclohexan-1-ol 8b. Following the typical
procedure above (rt, 0.5 h), the epoxide 8a (200 mg, 0.71 mmol)
was treated with ZnBr2
(3.2 mg, 0.014 mmol) to afford the
product 8b (180 mg) in 90% yield. δH 1.11 (m, 1H), 1.31
(m, 1H), 1.48 (m, 1H), 1.71 (m, 1H), 1.77–1.82 (m, 2H),
2.08 (m, 1H), 2.33 (m, 1H), 3.52 (br, 1H), 3.64 (br s, 1H), 7.09–
7.41 (m, 10H); δC 22.2, 23.5, 31.5, 32.1, 59.4, 76.8, 127.2, 127.7,
127.7, 127.8, 127.8, 128.6, 128.6, 128.8, 128.8, 131.6, 137.7,
140.0, 207.3; m/z (GC-MS) 280 (Mϩ, 2%), 262 (1), 158 (56), 130
(19), 115 (9), 105 (100), 91 (38), 77 (54); HRMS (EI): found
280.1447; calc. for C19
H20O2: 280.1463.
1-Hydroxyspiro[4.4]nonan-6-one 9b/c. Following the typical
procedure above (rt, 1.5 h), the epoxide 9a (200 mg, 1.30 mmol)
was treated with ZnBr2 (14.6 mg, 0.062 mmol) to afford the
product 9b (107 mg) and 9c (81 mg) in 94% total yield. δH 9b:
1.48–1.96 (10H), 2.25 (t, J 7.1, 2H), 3.52 (s, 1H), 3.94 (br s, 1H);
9c: 1.49–2.24 (m, 12H), 4.14 (t, J 6.9, 1H); δC 9b: 19.1, 21.2,
33.7, 34.3, 35.6, 38.8, 58.7, 80.3, 224.8; 9c: 19.5, 20.7, 30.2, 33.6,
34.4, 38.3, 60.2, 76.6, 223.6; m/z (GC-MS) 9b: 154 (Mϩ, 12%),
136 (29), 97 (100), 94 (29), 67 (54), 55 (38), 41 (32); 9c: 154 (Mϩ,
4%), 136 (4), 110 (26), 97 (100), 79 (29), 55 (51), 41 (57); HRMS
(EI): found 154.0982; calc. for C9H14O2: 154.0993.
1-Hydroxyspiro[5.7]tridecan-7-one 3b. Following the typical
procedure above (rt, 5 h), the epoxide 3a (200 mg, 0.95 mmol)
was treated with ZnBr2 (10.7 mg, 0.048 mmol) to afford the
product 3b (166 mg) in 83% yield. δH 1.18–2.04 (m, 18H), 2.32
(m, 1H), 2.49 (m, 1H), 3.27 (br, 1H), 3.74 (dd, J 3.4, 5.6, 1H);
δC 20.9, 21.0, 24.1, 24.7, 26.0, 28.1, 29.6, 29.7, 30.9, 37.0, 53.6,
72.2, 222.9; m/z (GC-MS) 210 (Mϩ, 35%), 182 (8), 149 (14), 139
(45), 111 (78), 98 (72), 81 (100), 55 (88); HRMS (EI): found
210.1624; calc. for C13H22O2: 210.1620.
(1S,5R)-2-Acetyl-2,5-dimethylcyclohexan-1-ol 4b/c. Follow-
ing the typical procedure above (rt, 95 h), the epoxide 4a (200
mg, 1.18 mmol) was treated with ZnBr2 (21.2 mg, 0.094 mmol)
to afford the product 4b/c (128 mg, 78:22) in 64% total yield.
1-Hydroxyspiro[4.5]decan-6-one 10b/c. Following the typical
procedure above (rt, 7 h), the epoxide 10a (200 mg, 1.19 mmol)
was treated with ZnBr2 (18.8 mg, 0.083 mmol) to afford the
J. Chem. Soc., Perkin Trans. 1, 2000, 3791–3794
3793