Cyclohexanone Oxocarbenium Ions
1
(500 MHz, CDCl3) δ 7.38-7.25 (m, 7.39H), 4.52 (s, 1.15H), 4.50
(s, 1.74H), 3.60-3.54 (m, 1H), 3.54-3.48 (m, 0.48H), 3.44
(s, 3.12H), 3.43 (s, 1.17H), 2.25-2.17 (m, 0.92H), 2.09-1.98
(m, 2.10H), 1.98-1.85 (m, 5.01H), 1.83-1.71 (m, 3.9H); 13C NMR
(125 MHz, CDCl3) δ 138.57, 138.55, 128.4, 128.4, 127.5, 127.5,
127.4, 127.3, 119.7, 119.6, 74.7, 74.2, 73.0, 72.2, 70.1, 69.9, 52.8,
and its minor diastereomer (0.03 g, 33%) H NMR (500 MHz,
CDCl3) δ 3.98-3.91 (m, 2H), 3.18 (s, 3H), 3.13 (s, 0.58H), 3.09
(ddd, J ) 10.4, 10.3, 3.9, 1H), 3.04-3.98 (m, 0.23H), 2.13-1.86
(m, 4.83H), 1.84-1.74 (m, 0.44H), 1.66 (q, J ) 7.4, 2H), 1.61-
1.34 (m, 5.01H), 1.25 (t, J ) 12.5, 1H), 1.21-1.14 (m, 0.41H),
1.03-0.98 (m, 0.23H), 0.87-0.84 (m, 3.54H); 13C NMR (125 MHz,
CDCl3) δ 83.38, 83.36, 77.2, 75.7, 67.7, 67.2, 48.5, 47.9, 41.7,
39.8, 36.2, 36.1, 32.3, 31.6, 30.8, 30.5, 29.1, 27.2, 26.5, 7.3, 6.8;
IR (thin film) 2937, 1461, 1357, 1128 cm-1; HRMS (EI) m/z calcd
for C10H17O (M - MeO)+ 153.1279, found 153.1279. Anal. Calcd
for C11H20O2: C, 71.70; H, 10.94. Found: C, 71.75; H, 10.73.
Benzyl Ether 24. To a cooled (-78 °C) solution of 23 (0.076
g, 0.248 mmol) in CH2Cl2 (2 mL) was added allyltributyltin (0.3
mL, 0.8 mmol), and the mixture was allowed to stir for 2 min,
then TMSOTf (0.05 mL, 0.4 mmol) was added. The solution was
warmed (0 °C), and NaHCO3 (2 mL saturated, aqueous) was added.
The layers were separated, and the aqueous layer was extracted
with CH2Cl2 (5 × 2 mL). The organic layers were combined,
filtered through Na2SO4, and concentrated in vacuo. A selectivity
of 82:18 was determined by subjecting the unpurified oil to GC:
tR (major) 18.1 min, tR (minor) 17.7 min. The resulting oil was
purified by flash chromatography (99:1 to 98:2 hexanes/EtOAc)
to afford the products 24 and a mixture of 24 and its minor
diastereomer (as a 3.7:1 mixture as determined by NMR) separately
as colorless oils. 24 (0.051 g, 65%): 1H NMR (500 MHz, CDCl3)
δ 7.36-7.30 (m, 4H), 7.25-7.22 (m, 1H), 5.74 (ddt, J ) 16.9,
10.4, 7.3, 1H), 5.03-4.99 (m, 2H), 4.61 (s, 2H), 3.17 (s, 3H), 2.16-
2.14 (m, 2H), 1.79-1.60 (m, 6H), 1.53 (ddd, J ) 13.8, 13.6, 4.6,
2H), 1.02 (s, 9H); 13C NMR (125 MHz, CDCl3) δ 140.4, 133.9,
128.2, 126.8, 126.7, 117.2, 79.7, 73.9, 65.7, 48.4, 41.7, 38.7, 29.3,
52.4, 30.5, 26.6, 26.0; IR (thin film) 2941, 2866, 1495, 1028 cm-1
;
HRMS (EI) m/z calcd for C15H20O2N (M + H)+ 246.1494, found
246.1503. Anal. Calcd for C15H19O2N: C, 73.44; H, 7.81; N, 5.71.
Found: C, 73.58; H, 7.88; N, 5.76.
Methyl Ether 21. To a cooled (-78 °C) solution of 20 (0.10 g,
0.50 mmol) in CH2Cl2 (2 mL) was added allyltrimethylsilane (0.35
mL, 2.1 mmol), the mixture was allowed to stir for 2 min, and
then TMSOTf (0.12 mL, 0.64 mmol) was added. The solution was
allowed to warm (0 °C), and NaHCO3 (2 mL saturated, aqueous)
was added. The layers were separated, and the aqueous layer was
extracted with CH2Cl2 (5 × 2 mL). The organic layers were
combined, filtered through Na2SO4, and concentrated in vacuo. A
selectivity of 90:10 was determined by 1H NMR spectroscopy. The
resulting oil was purified by flash chromatography (99:1 hexanes/
EtOAc) to afford the products 21 and a mixture of 21 and its minor
diastereomer (as a 5:1 mixture as determined by 1H NMR
spectroscopy) separately as colorless oils. 21 (0.03 g, 26%): 1H
NMR (500 MHz, CDCl3) δ 5.81 (ddt, J ) 17.4, 10.3, 7.3, 1H),
5.10-5.04 (m, 2H), 3.94-3.89 (m, 2H), 3.19 (s, 3H), 2.99 (ddd, J
) 11.2, 10.2, 3.9, 1H), 2.28 (ddt, J ) 14.4, 7.2, 1.3, 1H), 2.20
(ddt, J ) 14.4, 7.2, 1.3, 1H), 2.10 (dt, J ) 13.6, 3.1, 1H), 1.99-
1.88 (m, 3H), 1.83-1.74 (m, 1H), 1.63-1.48 (m, 2H), 1.24 (ddd,
J ) 14.4, 13.3, 4.0, 1H), 1.08 (dd, J ) 13.5, 12.6, 1H); 13C NMR
(125 MHz, CDCl3) δ 133.6, 117.6, 83.1, 75.5, 67.3, 48.1, 41.3,
39.8, 36.5, 31.7, 30.5, 26.4; IR (thin film) 3074, 2936, 1639, 1456,
1358, 1076 cm-1; HRMS (EI) m/z calcd for C12H21O2 (M + H)+
197.1542, found 197.1549. Anal. Calcd for C12H20O2: C, 73.43;
H, 10.27. Found: C, 73.72; H, 10.28. 21 and its minor diastere-
omer (0.06 g, 54%): 1H NMR (500 MHz, CDCl3) δ 5.87-5.76
(m, 1.18H), 5.14-5.04 (m, 2.43H), 3.98-3.81 (m, 2.44H), 3.24
(s, 0.54H), 3.19 (s, 3H), 3.09 (ddd, J ) 10.7, 9.9, 3.9, 0.20H), 2.99
(ddd, J ) 11.1, 10.3, 3.9, 1H), 2.43-2.42 (m, 0.34H), 2.28 (ddt, J
) 14.6, 7.2, 1.2, 1H), 2.20 (ddt, J ) 14.2, 7.3, 1.2, 1H), 2.12-
2.00 (m, 1.49H), 1.99-1.88 (m, 3.67H), 1.79 (tddd, J ) 12.4, 10.0,
6.6, 3.3, 1H), 1.63-1.36 (m, 2.96H), 1.32-1.21 (m, 1.63H), 1.08
(t, J ) 13.4, 12.6, 1H); 13C NMR (125 MHz, CDCl3) δ 133.6,
133.4, 117.6, 117.5, 83.1, 83.1, 75.5, 67.7, 67.2, 48.8, 48.1, 41.6,
41.3, 39.7, 37.1, 36.4, 36.4, 32.4, 31.7, 30.7, 30.4, 27.0, 26.4; IR
(thin film) 3074, 2938, 1640, 1358, 1075 cm-1; HRMS (EI) m/z
calcd for C12H21O2 (M + H)+ 197.1542, found 197.1549. Anal.
Calcd for C12H20O2: C, 73.43; H, 10.27. Found: C, 73.68; H, 10.55.
Methyl Ether 22. To a cooled (-78 °C) solution of 20 (0.10 g,
0.50 mmol) in CH2Cl2 (2 mL) was added a solution of Et2Zn (1 M
in hexanes, 0.64 mL, 0.64 mmol), the mixture was allowed to stir
for 10 s, and then TMSOTf (0.12 mL, 0.64 mmol) was added. The
solution was allowed to warm (0 °C), and NaHCO3 (2 mL saturated,
aqueous) was added. The layers were separated, and the aqueous
layer was extracted with CH2Cl2 (5 × 2 mL). The organic layers
were combined, filtered through Na2SO4, and concentrated in vacuo.
A selectivity of 88:12 was determined by subjecting the unpurified
oil to GC: tR (major) 9.3 min, tR (minor) 9.1 min. The resulting
oil was purified by flash chromatography (99:1 hexanes/EtOAc)
to afford the products 22 and a mixture of 22 and its minor
diastereomer (as a 5:1 mixture as determined by NMR) separately
as colorless oils. 22 (0.05 g, 45%): 1H NMR (500 MHz, CDCl3),
δ 3.98-3.91 (m, 2H), 3.18 (s, 3H), 3.09 (ddd, J ) 10.5, 10.0, 3.9,
1H), 2.06 (dt, J ) 12.4, 2.8, 1H), 2.04-1.93 (m, 2H), 1.89 (dtd, J
) 12.2, 2.8, 2.5, 1H), 1.66 (q, J ) 7.4, 2H), 1.61-1.34 (m, 4H),
1.25 (t, J ) 12.5, 1H), 0.85 (t, J ) 7.4, 3H); 13C NMR (125 MHz,
CDCl3) δ 83.4, 77.2, 67.7, 48.5, 41.7, 36.2, 32.3, 30.8, 27.2, 24.6,
6.8; IR (thin film) 2937, 1460, 1357, 1257 cm-1; HRMS (EI) m/z
calcd for C9H15O2 (M - C2H5)+ 155.1072, found 155.1078. 22
27.1, 24.0; IR (thin film) 3071, 2957, 1639, 1496, 1368, 1082 cm-1
Anal. Calcd for C21H32O2: C, 79.70; H, 10.19. Found: C, 79.54;
H, 10.33. Mixture of 24 and its minor diastereomer (0.020 g,
15%): H NMR (500 MHz, CDCl3) δ 7.40-7.31 (m, 5.25H), 7.27-
.
1
7.22 (m, 3.53H), 5.87 (ddt, J ) 17.2, 10.2, 7.1, 1H), 5.74 (ddt, J
) 17.6, 10.4, 7.3, 0.27H), 5.12-5.06 (m, 2H), 5.04-4.98 (m,
0.57H), 4.65 (s, 2H), 4.62 (s, 0.54H), 3.18-3.17 (m, 3.91H), 2.34-
2.33 (m, 2H), 2.16-2.15 (m, 0.55H), 1.99-1.94 (m, 2H), 1.80-
1.66 (m, 3.5H), 1.66-1.48 (m, 6.29H) 1.03-1.02 (m, 11.88H); 13
C
NMR (125 MHz, CDCl3) δ 140.2, 140.1, 134.2, 133.9, 128.3, 128.2,
126.94, 126.91, 126.86, 126.7, 117.2, 117.0, 79.7, 79.1, 76.8, 75.4,
65.7, 65.7, 48.4, 48.3, 41.8, 41.7, 38.7, 36.1, 29.7, 29.4, 27.1, 26.0,
24.0; IR (thin film) 3070, 3029, 2957, 1638, 1496, 1454 cm-1. Anal.
Calcd for C21H32O2: C, 79.70; H, 10.19. Found: C, 79.47; H, 10.40.
Benzyl Ether 25. To a cooled (-78 °C) solution of 23 (0.100
g, 0.33 mmol) in CH2Cl2 (2 mL) was added a solution of Et2Zn (1
M in hexanes, 0.39 mL, 0.39 mmol), the mixture was allowed to
stir for 10 s, and then TMSOTf (0.09 mL, 0.39 mmol) was added.
The solution was allowed to warm (0 °C), and NaHCO3 (2 mL,
saturated, aqueous) was added. The layers were separated, and the
aqueous layer was extracted with CH2Cl2 (5 × 2 mL). The organic
layers were combined, filtered through Na2SO4, and concentrated
in vacuo. A selectivity of 97:3 was determined by subjecting the
unpurified oil to GCMS: tR (major) 19.4 min, tR (minor) 19.0 min.
The resulting oil was purified by flash chromatography (98:2 to
97:3 hexanes/EtOAc) to afford the product as a colorless oil (0.078
g, 79%): 1H NMR (500 MHz, CDCl3) δ 7.41-7.39 (m, 2H), 7.34-
7.31 (m, 2H), 7.26-7.22 (m, 1H), 4.66 (s, 2H), 3.13 (s, 3H), 1.98-
1.92 (m, 2H), 1.72 (ddd, J ) 13.6, 13.5, 3.9, 2H), 1.62-1.55 (m,
4H), 1.48 (td, J ) 14.3, 4.0, 2H), 1.01 (s, 9H), 0.85 (t, J ) 7.4,
3H); 13C NMR (125 MHz, CDCl3) δ 140.1, 128.2, 126.9, 79.3,
75.4, 65.6, 48.0, 38.7, 29.6, 27.2, 26.1, 23.2, 6.9; IR (thin film)
2963, 2875, 1120, 1070 cm-1. Anal. Calcd for C20H32O2: C, 78.90;
H, 10.59. Found: C, 79.00; H, 10.56.
Acknowledgment. This research was supported by the
National Institutes of Health, National Institute of General
Medical Sciences (GM-61066). K.A.W. thanks Amgen, Johnson
J. Org. Chem, Vol. 71, No. 18, 2006 6857