3554 J . Org. Chem., Vol. 65, No. 11, 2000
Notes
mg (74% yield) of (+)-4 and epi-4 as a 93:7 mixture in favor of
(+)-4. Flash chromatography of the crude mixture afforded 330
mg (64%) of pure (+)-4 as crystalline material and 20 mg (4%)
of epi-4.
THF (8 mL) was cooled to 0 °C, and tetra-n-butylammonium
fluoride (1.0 M in THF, 1.4 mL, 1.4 mmol) was added dropwise.
The reaction mixture was warmed to room temperature and
stirred for 4 h. Cold water was added, and the resultant mixture
was extracted with CH2Cl2. The combined organic extracts were
washed with brine, dried, filtered, and concentrated. The
residual oil was chromatographed to afford 112 mg (94%) of the
alcohol (+)-7. Mp: 38-39 °C. [R]25D: +38.7 (c 1.0, CHCl3). IR
(neat): ν 3650, 3020, 1640, 1040, 900 cm-1. 1H NMR (200 MHz,
CDCl3): δ 0.54 (s, 3H), 0.80 (d, 3H, J ) 6.7 Hz), 1.00 (s, 3H),
1.26 (m, 1H), 1.35-1.63 (m, 3H), 2.00 (m, 2H), 2.30 (ddd, J )
12.7, 4.4, 2.9 Hz, 1H), 3.80 (m, 2H), 4.63 (br. s, 1H), 4.92 (br. s,
1H). 13C NMR (50 MHz, CDCl3): δ 14.9, 15.7, 26.5, 32.9, 37.0,
38.1, 42.0, 56.4, 59.5, 106.5, 148.0. Anal. Calcd for C11H20O: C,
78.51; H, 11.98. Found: C, 78.13; H, 12.01.
(+)-4. Mp: 57-59 °C. [R]25
: +6.1 (c 1.0, CHCl3). IR
D
1
(CDCl3): ν 3584, 1699, 1041 cm-1. H NMR (400 MHz, CDCl3):
δ 0.62 (s, 3H), 0.90 (d, J ) 6.6 Hz, 3H), 1.06 (s, 3H), 1.50-1.63
(m, 1H), 1.75-1.90 (m, 2H), 2.38 (m, 3H), 2.48 (dd, J ) 10.3, 4.2
Hz, OH), 3.67 (ddd, J ) 11.5, 10.3, 3.2 Hz, 1H), 3.99 (ddd, J )
11.5, 9.1, 4.2 Hz, 1H). 13C NMR (50 MHz, CDCl3): δ 14.9, 15.3,
26.4, 31.1, 40.9, 41.3, 41.9, 58.5, 62.3, 214.9. Anal. Calcd for
C10H18O2: C, 70.55; H, 10.66. Found: C, 70.38; H, 10.64.
epi-4. IR (CDCl3): ν 3583, 1697, 1035 cm-1 1H NMR (400
.
MHz, CDCl3): δ 0.88 (s, 3H), 0.99 (s, 3H), 1.13 (d, J ) 6.9 Hz,
3H), 1.57-1.67 (m, 1H), 1.66 (partially overlaped ddt, J ) 13.6,
6.5, 4.4 Hz, 1H), 2.05 (m, 1H), 2.28 (br. dt, J ) 14.6, 4.9 Hz,
1H), 2.42 (dddd, J ) 14.5, 11.4, 6.1, 1.1 Hz, 1H), 2.52 (ddd, J )
(-)-(1S,3R)-2,2,3-Tr im eth yl-6-m eth ylid en ecycloh exa n e-
1-ca r ba ld eh yd e ((-)-8). A solution of oxalyl chloride (159 mg,
1.25 mmol) in CH2Cl2 (10 mL) was cooled to -70 °C, and a
solution of dry DMSO (195 mg, 2.50 mmol) in CH2Cl2 (5 mL)
was added dropwise. The reaction mixture was stirred at -70
°C for 15 min, and a solution of alcohol (+)-7 (140 mg, 0.83 mmol)
in CH2Cl2 (5 mL) was added dropwise. After 30 min at -70 °C,
Et3N (0.70 mL, 5 mmol) was added, and the reaction mixture
was allowed to warm to room temperature over a period of 3 h.
Water was added, and the resultant mixture was extracted with
CH2Cl2. The combined organic extracts were washed with water
until neutral, dried, filtered, and concentrated. A column chro-
matography of the residue yielded 125 mg (90%) of aldehyde
(-)-8 as a colorless oil. [R]25D: -62.2 (c 1.0, CCl4). IR (neat): ν
3100, 1735, 1650, 900 cm-1. 1H NMR (200 MHz, CDCl3): δ 0.83
(d, J ) 5.7 Hz, 3H), 0.95 (s, 3H), 0.97 (s, 3H), 1.17-1.60 (m,
3H), 2.07 (br.t, J ) 12.7 Hz, 1H), 2.29 (br. dt, J ) 12.7, 3.3 Hz,
1H), 2.51 (br. d, J ) 4.8 Hz, 1H), 4.49 (br. s, 1H), 4.91 (br. s,
1H), 9.89 (d, J ) 4.8 Hz, 1H). 13C NMR (50 MHz, CDCl3): δ
14.8, 15.2, 27.0, 31.4, 35.9, 37.9, 41.6, 65.1, 109.3, 145.1, 205.2.
Anal. Calcd for C11H18O: C, 79.46; H, 10.91. Found: C, 79.34;
H, 10.95.
9.4, 3.6, 0.8 Hz, OH), 3.63 (m, 1H), 3.99 (t, J ) 10.3 Hz, 1H). 13
C
NMR (50 MHz, CDCl3): δ 14.5, 25.3, 25.6, 29.3, 37.4, 39.1, 40.6,
58.2, 59.2, 214.3. Anal. Calcd for C10H18O2: C, 70.55; H, 10.66.
Found: C, 70.39; H, 10.61.
(-)-(2S,4R)-2-(ter t-Bu t yld im et h ylsilyloxy)m et h yl-3,3,4-
tr im eth ylcycloh exa n -1-on e ((-)-5). The keto alcohol (+)-4
(600 mg, 3.54 mmol) was dissolved in DMF (20 mL), imidazole
(843 mg, 12.4 mmol) and tert-butyldimethylsilyl chloride (723
mg, 4.80 mmol) were added, and the mixture was stirred for 3
h at room temperature. The reaction was poured into water and
extracted with ether. The combined organic extracts were
washed with small portions of water and brine, dried, filtered,
and concentrated. Column chromatography gave 881 mg (87%)
of (-)-5. [R]25D: -24.9 (c 1.0, CHCl3). IR (neat): ν 1720, 1256,
1087, 838 cm-1. 1H NMR (200 MHz, CDCl3): δ 0.02 (s, 3H), 0.05
(s, 3H), 0.55 (s, 3H), 0.85 (s, 9H), 0.88 (d, J ) 6.7 Hz, 3H), 1.10
(s, 3H), 1.40-1.65 (m, 1H), 1.69-1.92 (m, 2H), 2.21-2.50 (m,
3H), 3.62 and 4.07 (ABX, J ) 10.2, 6.3, 4.1 Hz, 2H). 13C NMR
(50 MHz, CDCl3): δ -5.5, -5.4, 14.9, 15.1, 18.2, 25.9, 27.0, 32.0,
41.7, 41.8, 42.3, 57.9, 63.3, 211.2. Anal. Calcd for C16H32O2Si:
C, 67.55; H, 11.34. Found: C, 67.85; H, 11.29.
(+)-[(1S,3R)-2,2,3-Tr im eth yl-6-m eth ylid en ecycloh exyl]-
m eth yl-ter t-bu tyld im eth ylsilyl Oxid e (+)-6. P r ep a r a tion of
Lom ba r d o’s Rea gen t. To a suspension of Zn dust (2.87 g, 44
mmol) and CH2Br2 (1.01 mL, 14.4 mmol) in THF (25 mL), stirred
under an argon atmosphere at -40 °C was added dropwise neat
TiCl4 (1.13 mL, 10.3 mmol). The mixture was then allowed to
warm to 5 °C and was stirred for 3 days at this temperature to
produce a thick gray slurry of the active reagent.
(+)-(1′S,3′R,3E)-4-(2′,2′,3′-Tr im eth yl-6′-m eth ylid en ecyclo-
h ex-1′-yl)bu t-3-en -2-on e ((+)-(2R,6S)-cis-γ-Ir on e, (+)-1). A
mixture of diethyl (2-oxopropyl)phosphonate (352 mg, 1.81 mmol)
and Ba(OH)2‚8H2O (62 mg, 0.36 mmol, heated to 100-140 °C
for 2 h under a flux of argon before use) in THF (4 mL) was
stirred at room temperature for 30 min under an argon atmo-
sphere. A solution of aldehyde (-)-8 (100 mg, 0.60 mmol) in wet
THF (4 mL, 40:1 THF/H2O) was then added. After being stirred
for 18 h, the reaction mixture was diluted with CH2Cl2 and
washed with a saturated NaHCO3 aqueous solution and then
brine. The organic extracts were dried, filtered, and concen-
trated. Purification by column chromatography yielded 84 mg
(68%) of (+)-(2R,6S)-cis-γ-irone, (+)-1, as a colorless violet-like
scented oil, with diastereomeric excess (de) and enantiomeric
excess (ee) > 99% as determined by GC analyses. [R]25D: +0.4
To a CH2Cl2 (6 mL) solution of ketone (-)-5 (300 mg, 1.05
mmol), stirred at 5 °C under an argon atmosphere, was added
the Zn-CH2Br2-TiCl4 mixed methylenation reagent (2.5 equiv).
After being stirred for 4 h at this temperature, the reaction
mixture was diluted with CH2Cl2 and then poured into a cold
saturated NaHCO3 aqueous solution. The mixture was extracted
with ether. The combined extracts were washed with brine,
dried, filtered, and concentrated. The residue was subjected to
column chromatography to afford 270 mg (91%) of pure (+)-6
as an oil. [R]25D: +30.8 (c 1.0, CHCl3). IR (neat): ν 3088, 1648,
(c 3.0, CHCl3).22 IR (neat): ν 3055, 1675, 1650, 1635, 890 cm-1
.
1H NMR (400 MHz, CDCl3): δ 0.69 (s, 3H), 0.83 (d, J ) 6.5 Hz,
3H), 0.84 (s, 3H), 1.31 (m, 1H), 1.41 (m, 1H), 1.53 (m, 1H), 2.07
(br. td, J ) 13.4, 5.0 Hz, 1H), 2.26 (s, 3H), 2.31 (ddd, J ) 13.4,
4.4, 2.4 Hz, 1H), 2.52 (br. d, J ) 10.3 Hz, 1H), 4.40 (br. d, J )
1.3 Hz, 1H), 4.76 (br. d, J ) 1.3 Hz, 1H), 6.06 (d, J ) 15.9 Hz,
1H), 6.90 (dd, J ) 15.9, 10.3 Hz, 1H). 13C NMR (100 MHz,
CDCl3): δ 14.42, 15.92, 27.31, 27.76, 31.95, 36.33, 38.86, 42.03,
57.88, 108.76, 133.67, 147.18, 148.89, 198.18. Anal. Calcd for
1256, 1089, 836 cm-1 1H NMR (200 MHz, CDCl3): δ 0.03 (s,
.
6H), 0.57 (s, 3H), 0.79 (d, J ) 6.4 Hz, 3H), 0.86 (s, 9H), 1.02 (s,
3H), 1.24 (m, 1H), 1.38 (m, 1H), 1.50 (m, 1H), 1.87 (br. t, J ) 4
Hz, 1H), 2.02 (br. td, J ) 13.0, 5.4 Hz, 1H), 2.25 (ddd, J ) 12.6,
4.0, 2.0 Hz, 1H), 3.78 and 3.87 (ABX, J ) 10.5, 7.3, 4.1 Hz, 2H),
4.62 (br. s, 1H), 4.80 (br. s, 1H). 13C NMR (50 MHz, CDCl3): δ
-5.4, 14.8, 15.8, 18.2, 25.9, 26.7, 32.8, 37.3, 38.2, 42.4, 55.5, 60.8,
107.2, 148.0. Anal. Calcd for C17H34OSi: C, 72.27; H, 12.13.
Found: C, 72.46; H, 12.16.
C
14H22O: C, 81.50; H, 10.75. Found: C, 81.37; H, 10.74.
(+)-(1S,3R)-2,2,3-Tr im eth yl-6-m eth ylid en ecycloh exa n e-
1-m eth a n ol ((+)-7). A solution of (+)-6 (200 mg, 0.71 mmol) in
J O991903H