Nakai et al.
tography (silica gel, 50 g, elution with hexane/Et2O ) 50:1) to give
28 (107 mg, 27%). Colorless oil. Rf ) 0.22 (hexane/CH2Cl2 ) 3:1).
IR (film) 1645, 1621, 1564, 1465, 1254 cm-1. 1H NMR (500 MHz)
δ 0.10 (6H, s, SiMe2), 0.90 (9H, s, t-Bu), 1.08 (3H, d, J ) 6.6 Hz,
H-9), 2.49 (1H, dd-sep, d, J ) 6.9, 6.6, 1.4 Hz, H-8), 5.67 (1H, s,
H-4), 5.95 (1H, dd, J ) 15.8, 1.4 Hz, H-6), 6.38 (1H, d, J ) 18.8
Hz, H-2), 6.88 (1H, dd, J ) 15.8, 6.9 Hz, H-7), 7.14 (1H, d, J )
18.8 Hz, H-1). 13C NMR (125 MHz) δ -6.2 (SiMe2), 16.9 (CMe3),
21.6 (C-9), 26.6 (CMe3), 31.5 (C-8), 99. 7 (C-4), 125.1 (C-6),-
141.0 (C-2), 142.1 (C-1), 152.2 (C-7), 180.5, and 186.7 (C-3 and
C-5). HRMS calcd for C16H28O2Si 280.1859, found 280.1857.
General Procedure B for [3 + 4] Annulation Using 23 and
44: Reaction of 23f with Sodium Enolate of 44. To a cooled
(-80 °C) solution of NaHMDS (1.06 M in THF, 422 µL, 0.448
mmol) in THF (473 µL) was added dropwise a solution of 44 (101
mg, 0.448 mmol) in THF (895 µL), and then the solution was stirred
at the same temperature for 25 min. To this solution was added
dropwise a cooled (-80 °C) solution of 23f (80 mg, 0.344 mmol)
in THF (5.1 mL) over a period of 5 min, and the solution was
stirred at the same temperature for 7 min before addition of AcOH
(1 M in THF, 448 µL). The resulting mixture was diluted with
10% aqueous NH4Cl solution (20 mL), phases were separated, and
the aqueous phase was extracted with Et2O (5 mL × 2). Combined
organic phases were washed with saturated brine (30 mL), dried,
and concentrated. The residual oil was subjected to column
chromatography (florisil, 4 g, elution with hexane/Et2O ) 4:1) to
give a mixture of 20f and 43f. This mixture was separated by MPLC
(elution with hexane/Et2O/CH2Cl2 ) 20:1:1) to give 20f (102 mg,
65%) and 43f (16 mg, 11%). 20f: Colorless oil. Rf ) 0.42 (hexane/
(30 mL). The reaction mixture was allowed to warm to -30 °C
over a period of 15 min and then quenched with 10% aqueous NH4-
Cl solution (30 mL). The mixture was separated, and the aqueous
phase was extracted with Et2O (10 mL × 2). Combined organic
phases were washed with saturated brine (40 mL), dried, and
concentrated. The residual oil was subjected to column chroma-
tography (silica gel, 15 g; elution with hexane/Et2O ) 30:1) to
give 45 (88 mg, 42%) and an inseparable mixture of (E)- and (Z)-
46 (22 mg, 10%, E/Z ) 3.0). Compound 45 was determined to be
racemic using a Daicel Chiralcel OD-H column (4.6 mm × 250
mm): flow rate 0.5 mL/min, 254 nm, eluent hexane, tR ) 7.7 min,
8.2 min. 45: Colorless oil. Rf ) 0.52 (hexane/Et2O ) 5:1). IR (film)
3519, 1706, 1654, 1620, 1469, 1256 cm-1. 1H NMR (500 MHz) δ
0.09 and 0.11 (each 3H, s, SiMe2), 0.16 (6H, s, SiMe2), 0.67 (1H,
d, J ) 7.1 Hz, H-3), 0.85-0.95 (4H, m, H-3 and CHMe2), 0.88
and 0.92 (each 9H, s, t-Bu), 1.06 (3H, d, J ) 6.9 Hz, CHMe2),
1.18 (1H, sep, J ) 6.9 Hz, CHMe2), 2.90 (1H, s, OH), 5.55 (1H,
d, J ) 15.1 Hz, H-1′), 5.72 (1H, dd, J ) 11.7, 11.0 Hz, H-3′), 5.93
(1H, dd, J ) 15.1, 11.0 Hz, H-2′), 6.52 (1H, d, J ) 11.7 Hz, H-4′).
13C NMR (100 MHz) δ -5.1, -5.1, -3.8, and -3.0 (SiMe2), 18.0
and 18.3 (CHMe2), 18.1 and 18.4 (CMe3), 24.5 (C-3), 25.8 and
26.0 (CMe3), 31.6 (CHMe2), 62.7 and 64.4 (C-1, C-2), 112.9 (C-
3′), 126.5 (C-1′), 127.3 (C-2′), 144.8 (C-4′). HRMS calcd for
C22H43O3Si2 (M+ - H) 411.2751, found 411.2750. The relative
stereochemistry at C-1 and C-2 was assigned on the basis of the
observed correlation between the hydrogens at C-1′ and CHMe2 in
NOESY experiments. 46: (E/Z mixture) Colorless oil. Rf ) 0.48
(hexane/Et2O ) 5:1). IR (film) 1717, 1658, 1586, 1468, 1255 cm-1
.
HRMS calcd for C22H44O3Si2 412.2829, found 412.2823. 1H NMR
(500 MHz) signals assigned to (E)-46 in the mixture of (E)- and
(Z)-46. δ 0.12 and 0.14 (each 6H, s, SiMe2), 0.88 and 0.91 (each
9H, s, t-Bu), 1.08 (6H, d, J ) 7.1 Hz, H-1), 2.55 (2H, dd, J ) 7.6,
6.6 Hz, H-7), 2.78 (1H, sep, J ) 7.1 Hz, H-2), 3.19 (2H, s, H-4),
4.72 (1H, t, J ) 7.6 Hz, H-6), 4.95 (1H, dt, J ) 11.9, 6.6 Hz,
H-8), 6.24 (1H, d, J ) 11.9 Hz, H-9). 13C NMR (125 MHz) signals
assigned to (E)-46 in the mixture of (E)- and (Z)-46. δ -5.1, -4.4
(SiMe2), 18.1 and 18.7 (CMe3), 18.5 (C-1), 25.5 (C-7), 25.8 and
25.9 (CMe3), 39.5 (C-2), 44.6 (C-4), 108.7 (C-6), 110.2 (C-8), 140.9
(C-9), 146.1 (C-5), 211.1 (C-3). 1H NMR (500 MHz) signals
assigned to (Z)-46 in the mixture of (E)- and (Z)-46. δ 0.12 and
0.14 (each 6H, s, SiMe2), 0.91 and 0.92 (each 9H, s, t-Bu), 1.35
(6H, d, J ) 6.9 Hz, H-1), 2.64 (2H, dd, J ) 7.1, 6.6 Hz, H-7), 2.86
(1H, sep, J ) 6.9 Hz, H-2), 3.10 (2H, s, H-4), 4.53 (1H, t, J ) 7.1
Hz, H-6), 4.95 (1H, dt, J ) 11.9, 6.6 Hz, H-8), 6.24 (1H, d, J )
11.9 Hz, H-9). 13C NMR (125 MHz) signals assigned to (Z)-46 in
the mixture of (E)- and (Z)-46. δ -5.1, -3.8 (SiMe2), 18.4 and
18.7 (CMe3), 18.5 (C-1), 23.8 (C-7), 25.8 and 25.9 (CMe3), 38.9
(C-2), 49.8 (C-4), 110.0 (C-8), 112.0 (C-6), 140.8 (C-9), 144.5 (C-
5), 211.9 (C-3). The enol silyl ether geometries were determined
on the basis of NOESY experiments.
(1S,4S,5S)-2-(tert-Butyldimethylsilyloxy)-4-((E)-2-(tert-
butyldimethylsilyloxy)vinyl)bicyclo[3.3.2]dec-2-en-9-one (48). To
a cooled (-80 °C) solution of KHMDS (0.51 M in toluene, 1.44
mL, 0.735 mmol) in THF (397 µL) was added dropwise a solution
of 2-cycloheptenone (81 mg, 0.735 mmol) in THF (735 µL) over
a period of 2 min, and then the solution was stirred at the same
temperature for 30 min. To this solution was added dropwise a
cooled (-80 °C) solution of (-)-trans-18 (200 mg, 0.612 mmol)
in THF (10.8 mL) over a period of 12 min. After stirring at -80
°C for 5 min, the reaction mixture was quenched by addition of
AcOH (1 M in THF, 735 µL). The resulting mixture was diluted
with 10% aqueous NH4Cl solution (20 mL), phases were separated,
and the aqueous phase was extracted with Et2O (5 mL × 2).
Combined organic phases were washed with saturated brine
(20 mL), dried, and concentrated. The residual oil was subjected
to column chromatography (silica gel, 11 g, elution with hexane/
Et2O ) 22:1) to give 48 (93 mg, 35%). Colorless oil. Rf ) 0.37
(hexane/Et2O ) 6:1). [R]28D +1.6 (c 1.0, CHCl3). The optical purity
was determined to be 62% ee using a Daicel Chiralcel OD-H
1
Et2O ) 5:1). IR (film) 1712, 1426, 1654, 1257 cm-1. H NMR
(500 MHz) δ 0.11 and 0.11 (each 3H, s, SiMe2But), 0.45 and 0.46
(each 3H, s, SiMe2Ph), 0.85 and 0.91 (each 3H, d, J ) 6.6 Hz,
CHMe2), 0.90 (9H, s, t-Bu), 1.63 (1H, d-sep, J ) 6.6, 6.6 Hz,
CHMe2), 1.91 (1H, dddd, J ) 11.7, 6.6, 4.8, 3.0 Hz, H-6), 2.37-
(1H, dd, J ) 14.7, 4.8 Hz, H-7), 2.44 (1H, dd, J ) 14.7 Hz, 11.7,
H-7), 2.84 (1H, d, J ) 16.3 Hz, H-2), 2.99 (1H, ddd, J ) 8.2, 6.9,
3.0 Hz, H-5), 3.58 (1H, ddd, J ) 16.3, 2.1, 2.1 Hz, H-2), 4.84
(1H, dd, J ) 6.9, 2.5 Hz, H-4), 4.86 (1H, dd, J ) 11.9, 8.2 Hz,
H-1′), 6.11 (1H, d, J ) 11.9 Hz, H-2′), 7.34-7.43 (3H, m, Ph),
7.55-7.59 (2H, m, Ph). 13C NMR (125 MHz) δ -5.0 (SiMe2But),
-1.0 and -1.0 (SiMe2Ph), 18.5 (CMe3), 20.1 and 21.5 (CHMe2),
25.9 (CMe3), 29.5 (CHMe2), 36.9 (C-5), 43.5 (C-7), 46.0 (C-6),
49.5 (C-2), 109.9 (C-1′), 112.8 (C-4), 128.1, 130.1, 133.5, 137.3
(Ph), 142.2 (C-2′), 144.5 (C-3), 208.6 (C-1). HRMS calcd for
C26H42O3Si2 458.2672, found 458.2682. 43f: Colorless oil. Rf )
1
0.42 (hexane/Et2O ) 5:1). IR (film) 1712, 1657, 1257 cm-1. H
NMR (500 MHz) δ 0.11 (6H, s, SiMe2But), 0.49 and 0.50 (each
3H, s, SiMe2Ph), 0.73 and 0.77 (each 3H, d, J ) 6.4 Hz, CHMe2),
0.91 (9H, s, t-Bu), 1.37 (1H, d-sep, J ) 10.3, 6.4 Hz, CHMe2),
1.67 (1H, ddd, J ) 10.3, 7.3, 4.4 Hz, H-5), 2.22 (1H, dd, J ) 10.3,
7.6 Hz, H-7), 2.60 (1H, dd, J ) 10.8, 10.3 Hz, H-7), 2.74 (1H,
dddd, J ) 10.8, 10.5, 7.3, 4.4 Hz, H-6), 2.77 (1H, d, J ) 19.7 Hz,
H-2), 3.30 (1H, d, J ) 19.7 Hz, H-2), 4.70 (1H, dd, J ) 7.3, 2.3
Hz, H-4), 4.73 (1H, dd, J ) 11.9, 10.5 Hz, H-1′), 6.23 (1H, d, J )
11.9 Hz, H-2′), 7.36-7.43 (3H, m, Ph), 7.57-7.62 (2H, m, Ph).
13C NMR (125 MHz) δ -5.1 (SiMe2But), -1.1 and -1.0 (SiMe2-
Ph), 18.5 (CMe), 20.0 and 21.9 (CHMe2), 25.9 (CMe3), 30.2
(CHMe2), 41.7 (C-6), 45.5 (C-5), 48.4 (C-7), 50.8 (C-2), 110.6 and
110.7 (C-4 and C-1′), 128.2, 130.2, 133.6, 137.0 (Ph), 141.6 (C-
2′), 147.6 (C-3), 210.1 (C-1). HRMS calcd for C26H42O3Si2
458.2672, found 458.2678.
Reaction of (-)-trans-18 with Lithium Enolate of 3-Methyl-
2-butanone. To a cooled (-80 °C) solution of lithium diisopro-
pylamide (LDA) prepared from diisopropylamine (82 µL, 0.584
mmol) and n-BuLi (2.25 M in hexane, 248 µL, 0.559 mmol) in
THF (0.3 mL) was added dropwise a solution of 3-methyl-2-
butanone (48 mg, 0.569 mmol) in THF (0.6 mL). After being stirred
at -80 °C for 15 min, the solution was added dropwise to a cooled
(-80 °C) solution of (-)-trans-18 (166 mg, 0.508 mmol) in THF
1386 J. Org. Chem., Vol. 72, No. 4, 2007