Synthesis of 5-(tert-Butyldimethylsiloxy)-2-cyclohexenone
J. Am. Chem. Soc., Vol. 121, No. 15, 1999 3647
1331, 1255, 1178, 1084, 1003, 937, 912, 837, 812, 775, 721, 665 cm-1
.
(m, 1H), 2.49-2.32 (m, 3H), 2.32-2.15 (m, 1H), 2.00-1.85 (m, 2H),
1.90 (br d, J ) 13.5 Hz, 1H), 1.47 (ddd, J ) 13.5, 11.4 and 2.1 Hz,
1H), 1.37-1.24 (m, 6H), 0.90 (t, J ) 7.2 Hz, 3H), 0.86 (s, 9H), 0.04
(s, 3H), 0.03 (s, 3H). 13C NMR: δ 210.4, 68.9, 49.5, 47.9, 38.9, 36.0,
32.2, 28.7, 25.5, 22.5, 17.8, 13.9, -5.1. IR (neat): 2929, 1718, 1464,
1253, 1101, 1045, 891, 837, 777 cm-1. Anal. Calcd for C16H32O2Si:
C, 67.55; H, 11.34. Found: C, 67.81; H, 11.38.
Anal. Calcd for C15H30O3Si: C, 62.89; H, 10.55. Found: C, 62.58; H,
1
10.50. Minor diastereoisomer: H NMR: δ 1.12 (d, 7.5 Hz, 3H).
(2S,3S)-Ethyl 2-Benzyl-3-(tert-butyldimethylsiloxy)-5-hexenoate
1
(11b). H NMR: δ 7.28-7.11 (m, 5H), 5.99-5.82 (m, 1H), 5.18-
5.08 (m, 2H), 4.10-3.88 (m, 3H), 2.90-2.77 (m, 3H), 2.48-2.24 (m,
2H), 1.02 (t, J ) 7.5 Hz, 3H), 0.87 (s, 9H), 0.07 (s, 3H), 0.04 (s, 3H).
13C NMR: δ 173.7, 139.6, 134.1, 129.0, 128.3, 126.2, 117.8, 72.6,
60.0, 53.6, 38.6, 33.7, 25.6, 17.9, 13.9, -4.4, -5.1. IR (neat): 2929,
(3S,5S)-3-(tert-Butyldimethylsiloxy)-5-methylcyclohexanone (Table
1
1, Entry 1). H NMR: δ 4.43-4.37 (m, 1H), 2.46-2.31 (m, 4H),
2856, 1733, 912. Anal. Calcd for C21H34O3Si: C, 69.56; H, 9.45 cm-1
Found: C, 69.64; H, 9.57.
.
2.00-1.80 (m, 2H), 1.48 (ddd, J ) 13.5, 11.4 and 2.1 Hz, 1H), 1.02
(d, J ) 6.6 Hz, 3H), 0.85 (s, 9H), 0.04 (s, 3H), 0.03 (s, 3H). 13C NMR:
δ 210.4, 69.0, 49.7, 49.1, 40.9, 27.6, 25.6, 21.8, 17.8, -5.1. IR (neat):
(1RS,2S,3S)-1-Hydroxy-2-methyl-3-(tert-butyldimethylsiloxy)-
bicyclo[3.1.0]hexane (12a). Obtained as a complex mixture of dias-
tereoisomers, the characterization of which was difficult. Following
are some characteristic signals: 1H NMR: δ 4.03 (ddd, J ) 6.0, 6.0
and 1.5 Hz, 1H), 3.86 (m, 1H), 2.38 (dqd, J ) 6.9, 6.9 and 2.4 Hz,
1H), ..., 1.52 (d, J ) 13.8 Hz, 1H), ..., 1.04 (d, J ) 6.9 Hz, 3H), ...,
0.86 (s, 9H), ..., 0.71-0.64 (m, 1H), 0.58-0.53 (m, 1H). 13C NMR: δ
73.2, 67.8, 45.4, 37.2, 31.5, 25.7, 23.3, 22.6, 17.9, 16.4, 14.0, 9.6, -4.8,
-5.3. IR (neat): 3309, 2956, 2929, 2858, 1471, 1361, 1255, 1049,
1020, 837, 775 cm-1. Anal. Calcd for C13H26O2Si: C, 64.41; H, 10.81.
Found: C, 64.49; H, 10.92.
2954, 2929, 2856, 1718, 1251, 1116, 1088, 1043, 887, 837, 777 cm-1
.
Anal. Calcd for C13H26O2Si: C, 64.41; H, 10.81. Found: C, 64.51; H,
10.35.
(3S,5S)-3-(tert-Butyldimethylsiloxy)-5-{1-[(3S)-3,7-dimethyl-6-
octenyl]}cyclohexanone (Table 1, Entry 3). To a freshly prepared
THF solution of (2-thienyl)cyanocuprate19 was added at -78 °C a THF
(1 mL) solution of (S)-1, and the resulting mixture was stirred for 1 h
at -78 °C. The reaction was quenched and the product extracted and
1
purified (60%, not optimized) in the usual way. H NMR: δ 5.08 (br
t, J ) 7.2 Hz, 1H), 4.41-4.35 (m, 1H), 2.47-2.30 (m, 3H), 2.27-
2.10 (m, 1H), 2.06-1.83 (m, 4H), 1.67 (s, 3H), 1.58 (s, 3H), 1.45 (br
t, J ) 13.5 Hz, 1H), 1.44-1.20 (m, 5H), 1.20-1.03 (m, 2H), 0.90-
0.78 (m, 12H), 0.03 (s, 3H), 0.02 (s, 3H). 13C NMR: δ 210.4, 131.2,
124.9, 68.9, 49.5, 48.1, 38.8, 36.9, 33.7, 33.6, 32.6, 32.3, 25.6, 25.55,
25.4, 19.3, 17.8, 17.5, -5.1. IR (neat): 2927, 1718, 1459, 1373, 1253,
1091, 1035, 892, 837, 804, 777, 692 cm-1. Anal. Calcd for
C22H42O2Si: C, 72.07; H, 11.55. Found: C, 71.94; H, 11.55.
(3S,5S)-3-(tert-Butyldimethylsiloxy)-5-(2-butyl)cyclohexanone (Table
1, Entry 4). Mixture of two diastereoisomers at CH-CH3. 1H NMR: δ
4.48-4.39 (m, 2H), 2.44-2.20 (m, 8H), 2.16-1.94 (m, 2H), 1.84-
1.72 (m, 2H), 1.62-1.08 (m, 8H), 0.91-0.81 (m, 30H), 0.02 (s, 6H),
0.01 (s, 6H). 13C NMR: δ 211.0, 68.9, 49.4, 49.3, 46.0, 44.1, 38.5,
38.4, 36.5, 36.0, 34.2, 26.5, 26.2, 25.6, 17.8, 15.2, 15.1, 11.5, 11.4,
-5.1, -5.1. IR (neat): 2958, 2858, 1718, 1461, 1251, 1103, 1076,
1047, 893, 837, 775 cm-1. Anal. Calcd for C16H32O2Si: C, 67.55; H,
11.34. Found: C, 67.56; H, 11.23.
(1RS,2S,3S)-1-Hydroxy-2-benzyl-3-(tert-butyldimethylsiloxy)-
bicyclo[3.1.0]hexane (12b). Obtained as a 7:3 mixture of diastereoi-
1
somers. H NMR: δ 7.40-7.15 (m, 5H), 4.20 (ddd, J ) 6.0, 6.0 and
1.2 Hz, 1H), 4.02-3.88 (m, 1H), 3.23 (dd, J ) 14.4 and 4.0 Hz, 1H),
2.97-2.81 (m, 2H), 2.81-2.68 (m, 2H), 2.22 (ddd, J ) 13.5, 5.0 and
5.0 Hz, 1H), 1.90-1.63 (m, 2H), 1.58 (d, J ) 13.5 Hz, 1H), 1.46-
1.38 (m, 1H), 1.36-1.25 (m, 2H), 1.19 (dd, J ) 4.8 and 4.8 Hz, 1H),
0.92 (s, 9H), 0.89 (s, 9H), 0.81-0.74 (m, 1H), 0.57 (dd, J ) 5.5 and
4.5 Hz, 1H), 0.06-0.15 (m, 12H). IR (neat): 3359, 2954, 2929, 2856,
1716, 1471, 1255, 1103, 1057, 837, 775, 734, 698 cm-1. Anal. Calcd
for C19H30O2Si: C, 71.64; H, 9.49. Found: C, 71.80; H, 9.61.
(5S,6S)-5-(tert-Butyldimethylsiloxy)-6-methyl-2-cyclohexenone (2a).
Obtained as a 9:1 mixture of diastereoisomers: [R]23 ) - 28.98 (c
D
1
0.25, CHCl3). Major diastereoisomer: H NMR: δ 6.75 (dddd, J )
10.2, 3.9, 3.9 and 0.6 Hz, 1H), 6.01 (ddd, J ) 10.2, 2.1 and 2.1 Hz,
1H), 4.21 (ddd, J ) 6.0, 4.2 and 0.9 Hz, 1H), 2.60-2.37 (m, 3H), 1.13
(d, J ) 6.9 Hz, 3H), 0.84 (s, 9H), 0.07 (s, 6H). 13C NMR: δ 201.8,
145.1, 129.3, 71.0, 48.3, 33.5, 25.5, 17.8, 10.5, -4.9, -5.0. IR (neat)
2929, 1682, 1462, 1390, 1255, 1207, 1109, 1063, 1020, 883, 837, 775,
665. Anal. Calcd for C13H24O2Si: C, 64.95; H, 10.06. Found: C, 64.93;
H, 9.99. Minor diastereoisomer: 1H NMR: δ 6.85-6.78 (m, 1H), 3.77
(ddd, J ) 9.9, 8.4 and 4.8 Hz, 1H), 1.16 (d, J ) 6.9 Hz, 3H). 13C
NMR: δ 145.8, 129.6, 72.6, 51.1, 35.4, 11.2.
(3S,5S)-3-(tert-Butyldimethylsiloxy)-5-tert-butylcyclohexanone
1
(Table 1, Entry 5). Mp ) 46-47 °C. H NMR: δ 4.49-4.43 (m,
1H), 2.49-2.40 (br d, J ) 10.5 Hz, 1H), 2.40-2.34 (m, 2H), 2.12-
1.88 (m, 3H), 1.46 (ddd, J ) 13.5, 12.0 and 1.8 Hz 1H), 0.89 (s, 9H),
0.85 (s, 9H), 0.04 (s, 3H), 0.03 (s, 3H). 13C NMR: δ 211.6, 68.8, 49.1,
43.4, 41.8, 33.5, 32.0, 27.1, 25.5, 17.8, -5.1, -5.2. IR (neat): 2954,
2856, 1701, 1471, 1365, 1253, 1095, 1034, 893, 837, 777 cm-1. Anal.
Calcd for C16H32O2Si: C, 67.55; H, 11.34. Found: C, 67.45; H, 11.15.
(3S,5S)-3-(tert-Butyldimethylsiloxy)-5-phenylcyclohexanone (Table
1, Entry 6). 1H NMR: δ 7.39-7.30 (m, 2H), 7.29-7.14 (m, 3H),
4.55-4.48 (m, 1H), 3.55 (dddd, J ) 12.6, 12.6, 4.5 and 4.5 Hz, 1H),
2.67-2.43 (m, 4H), 2.14-1.93 (m, 2H), 0.89 (s, 9H), 0,07 (s, 3H),
0.06 (s, 3H). 13C NMR: δ 209.5, 144.2, 128.8, 126.8, 126.7, 68.8,
49.0, 48.7, 40.1, 38.0, 25.6, 17.9, -5.10, -5.13. IR (neat): 2954, 2856,
1718, 1251, 1095, 1037, 837, 777, 698 cm-1. Anal. Calcd for C18H28O2-
Si: C, 71.00; H, 9.27. Found: C, 70.95; H, 8.94.
(5S,6S)-5-(tert-Butyldimethylsiloxy)-6-benzyl-2-cyclohexenone (2b).
Obtained as a single diastereoisomer. [R]23D ) + 69.5 (c 1.11 CHCl3).
1H NMR: δ 7.35-7.15 (m, 5H), 6.71 (dddd, J ) 9.9, 3.9, 3.9 and 1.2
Hz, 1H), 6.07 (ddd, J ) 9.9, 1.8 and 1.8 Hz, 1H), 4.27-4.21 (m, 1H),
3.25 (dd, J ) 14.1 and 5.1 Hz, 1H), 2.84-2.75 (m, 1H), 2.70 (ddd, J
) 8.1, 5.4 and 2.7 Hz, 1H), 2.50 (ddd, J ) 3.9, 3.9 and 2.1 Hz 2H),
0.87 (s, 9H), 0.06 (s, 3H), 0.02 (s, 3H). 13C NMR: δ 199.7, 144.0,
140.3, 129.7, 129.2, 128.4, 126.1, 69.2, 55.9, 34.5, 30.6, 25.6, 17.9,
-4.6, -4.9. IR (neat) 2927, 1681, 1454, 1390, 1259, 1095, 835, 777,
698. Anal. Calcd for C19H28O2Si: C, 72.10; H, 8.92. Found: C, 72.28;
H, 8.79.
(3S,5S)-3-(tert-Butyldimethylsiloxy)-5-ethenylcyclohexanone (Table
1
1, Entry 7). H NMR: δ 5.81 (ddd, J ) 16.8, 10.5 and 6.5 Hz, 1H),
5.07-4.98 (m, 2H), 4.45-4.39 (m. 1H), 3.03-2.88 (m, 1H), 2.51-
2.38 (m, 3H), 2.15 (ddd, J ) 14.0, 11.5 and 0.9 Hz, 1H), 1.98-1.88
(m, 1H), 1.65 (ddd, J ) 13.5, 11.5 and 2.1 Hz, 1H), 0.86 (s, 9H), 0.05
(s, 3H), 0.04 (s, 3H). 13C NMR: δ 209.4, 141.4, 113.7, 68.6, 49.3,
46.5, 38.5, 36.0, 25.6, 17.8, -5.10, -5.13. IR (neat): 2929, 2856, 1718,
1641, 1471, 1417, 1361, 1253, 1086, 1041, 891, 837, 777 cm-1. Anal.
Calcd for C14H26O2Si: C, 66.09; H, 10.30. Found: C, 66.14; H, 10.80.
Reactions of Lower-Order Cyanocuprates onto 1. (3S,5R)-3-
(tert-Butyldimethylsiloxy)-5-butylcyclohexanone. Typical procedure
for the reaction of lower-order cyanocuprates on enones 1 and 2 (Table
2, entry 3): Into a flame-dried Schlenck tube flushed with argon were
introduced CuCN (107 mg, 1.2 mmol) and dry Et2O (20 mL). The
suspension was cooled to -78 °C under magnetic agitation, and BuLi
(0.75 mL, 1.59 M in n-hexane, 1.2 mmol) was slowly added. The
resulting mixture was stirred for 30 min at -78 °C (until complete
Reactions of Higher-Order Cyanocuprates onto 1. (3S,5S)-3-(tert-
Butyldimethylsiloxy)-5-butylcyclohexanone. Typical procedure for the
reaction of higher-order cyanocuprates on enones 1 and 2 (Table 1,
entry 2): Into a flame-dried Schlenck tube flushed with argon were
introduced CuCN (107 mg, 1.2 mmol) and distilled THF (20 mL). The
mixture was cooled to -78 °C under magnetic agitation, and BuLi
(1.51 mL, 1.59 M in n-hexane, 2.4 mmol) was slowly added. The
resulting mixture was stirred for 30 min at -78 °C, and the enone 1
(226 mg, 1 mmol) in a solution in THF (1 mL) was added dropwise at
-78 °C (addition time: about 5 min). Stirring was continued for 30
min before quenching with saturated NH4OH. Extraction with Et2O,
drying (MgSO4) and evaporation of the solvent gave a colorless oil,
cis:trans ) <2:>98 by GC measurement; purification by flash
chromatography (SiO2, hexane:Et2O ) 9:1) yielded the title product
as a colorless oil (261 mg, 0.92 mmol, 92%). 1H NMR: δ 4.43-4.37