silica gel column chromatography (hexanes) to afford 637 mg of
the aryl bromide as a colorless oil (94% yield): IR (neat) νmax 2968,
2930, 2869, 1554 cm-1; 1H NMR (500 MHz, CDCl3) δ 7.40 (s, 1
H), 2.57 (t, J ) 6.5 Hz, 2 H), 2.36 (s, 3 H), 2.18 (s, 3 H), 1.83-1.78
(m, 2 H), 1.59-1.53 (m, 2 H), 1.25 (s, 6 H); 13C NMR (100 MHz,
CDCl3) δ 145.3 (C), 136.6 (C), 133.9 (C), 132.6 (C), 128.2 (CH),
123.1 (C), 38.4 (CH2), 33.9 (C), 31.9 (2xCH3), 28.5 (CH2), 19.935
(CH3), 19.5 (CH2), 16.6 (CH3); HRMS m/z calcd for C14H19Br
266.0670 (M+), found 266.0680. Step 2: A stirred solution of the
bromide (283 mg, 1.064 mmol), tributylvinyltin (560 µL, 1.916
mmol), Pd(PPh3)4 (98 mg, 0.085 mmol), and toluene (7 mL) in a
microwave cell was deoxygenated by bubbling argon through it
for 15 min. The reaction mixture was heated at 150 °C in the
microwave oven for 2 h. After cooling to room temperature, the
mixture was diluted with hexanes (25 mL) and washed with H2O
(20 mL), 10% aqueous NH4OH (20 mL), and saturated aqueous
NaCl (20 mL). The organic layer was dried and concentrated. The
residue was purified by silica gel column chromatography (hexanes)
to afford 211 mg of 26 as a pale yellow oil (93% yield): IR (neat)
method to the synthesis of other rearranged labdanes is
underway and will be reported in due course.
Experimental Section
5,6-Dimethyl-1,2,3,4-tetrahydronaphthalene (23). AgOTf (388
mg, 1.51 mmol) and Au(PPh3)Cl (747 mg, 1.51 mmol) were
transferred to a flame-dried flask containing CH2Cl2 (230 mL).
Then, a solution of 22 (4.48 g, 25.15 mmol) in CH2Cl2 (20 mL)
was added via cannula. After stirring at room temperature for 21 h,
the reaction mixture was filtered through Celite. The fritted glass
funnel was rinsed with Et2O (50 mL), and the filtrate was
concentrated. The residue was purified by silica gel column
chromatography (hexanes) to afford 2.76 g of 23 as a colorless oil
(69% yield): IR (neat) νmax 2945, 2918, 2861 cm-1; 1H NMR (400
MHz, CDCl3) δ 6.93 (d, J ) 7.7 Hz, 1 H), 6.85 (d, J ) 7.7 Hz, 1
H), 2.75 (t, J ) 6.2 Hz, 2 H), 2.66 (t, J ) 6.4 Hz, 2 H), 2.26 (s, 3
H), 2.13 (s, 3 H), 1.86-1.78 (m, 2 H), 1.77-1.71 (m, 2 H); 13C
NMR (100 MHz, CDCl3) δ 135.3 (C), 134.9 (C), 134.8 (C), 133.5
(C), 127.0 (CH), 126.5 (CH), 30.1 (CH2), 27.3 (CH2), 23.7 (CH2),
22.8 (CH2), 20.4 (CH3), 14.8 (CH3); HRMS m/z calcd for C12H16
160.1252 (M+), found 160.1267.
1
νmax 3085, 2960, 2926, 2865, 1622 cm-1; H NMR (400 MHz,
CDCl3) δ 7.32 (s, 1 H), 7.01 (dd, J ) 17.3, 10.9 Hz, 1 H), 5.51
(dd, J ) 17.3, 1.7 Hz, 1 H), 5.24 (dd, J ) 10.9, 1.7 Hz, 1 H), 2.65
(t, J ) 6.5 Hz, 2 H), 2.24 (s, 3 H), 2.15 (s, 3 H), 1.86-1.80 (m, 2
H), 1.64-1.61 (m, 2 H), 1.31 (s, 6 H); 13C NMR (100 MHz, CDCl3)
δ 143.3 (C), 136.8 (CH), 135.2 (C), 134.7 (C), 134.5 (C), 130.9
(C), 122.1 (CH), 114.9 (CH2), 38.7 (CH2), 33.9 (C), 32.0 (2xCH3),
28.7 (CH2), 16.7 (CH2), 15.8 (CH3), 15.6 (CH3); HRMS m/z calcd
for C16H22 214.1721 (M+), found 214.1730.
5,6-Dimethyl-3,4-dihydro-2H-naphthalenone (24). A 10% aque-
ous CrO3 acetic solution (23.42 mmol, 22.2 mL in AcOH/H2O)
was added to a solution of 23 (750 mg, 4.68 mmol) in glacial AcOH
(120 mL). The resulting dark brown reaction mixture was stirred
at room temperature for 2.5 h. H2O (200 mL) was added, and the
aqueous layer was extracted with Et2O (4 × 100 mL). Combined
organic phases were washed with H2O and NaHCO3 (saturated),
dried, and concentrated. The residue was purified by silica gel
column chromatography (5% EtOAc/hexanes) to afford 370 mg of
24 as a pale yellow solid (45% yield): mp 67-68.5 °C; IR (neat)
Ethyl (E)-3-methyl-5-(3,4,8,8-tetramethyl-5,6,7,8-tetrahydronaph-
thalen-2-yl)-pent-2-enoate (28). To 9-BBN (2.12 mL of a 0.5 M
solution in THF, 1.06 mmol) was added a solution of 26 (75.6 mg,
0.35 mmol) in THF (750 µL) over 2 min. The mixture was heated
under reflux for 1 h. In a separate flask, a solution of 27 (85 mg,
0.35 mmol) in DMF (500 µL) was added to a stirred mixture of
Cs2CO3 (230 mg, 0.71 mmol), PdCl2(dppf) ·CH2Cl2 (29 mg, 10 mol
%), Ph3As (11 mg, 10 mol %), DMF (1 mL), and H2O (230 µL,
36 molar equiv). The resulting mixture was stirred for 5 min. After
addition of the above THF solution, the reaction mixture was heated
at 80 °C for 2 h. After cooling down to room temperature, water
was added (3 mL) and the mixture was extracted with Et2O (3 ×
5 mL). Combined organic layers were washed with NaCl (satu-
rated), dried, and concentrated. The residue was purified by silica
gel column chromatography (10 f 50% benzene/hexanes) to afford
86 mg of 28 as a white solid (74% yield): mp 73-76 °C; IR (neat)
ν
max 2933, 2860, 1682, 1594 cm-1; 1H NMR (500 MHz, CDCl3) δ
7.83 (d, J ) 8.0 Hz, 1 H), 7.08 (d, J ) 8.0 Hz, 1 H), 2.87 (t, J )
6.2 Hz, 2 H), 2.60-2.57 (m, 2 H), 2.32 (s, 3 H), 2.20 (s, 3 H),
2.15-2.09 (m, 2 H); 13C NMR (125 MHz, CDCl3) δ 198.7 (C),
142.5 (C), 142.4 (C), 134.4 (C), 130.9 (C), 128.0 (CH), 124.5 (CH),
38.3 (CH2), 26.9 (CH2), 22.6 (CH2), 21.1 (CH3), 14.9 (CH3); HRMS
m/z calcd for C12H14O 174.1045 (M+), found 174.1044.
1,1,5,6-Tetramethyl-1,2,3,4-tetrahydronaphthalene (25). To a
solution of freshly distilled TiCl4 (625 L, 5.70 mmol) in CH2Cl2
(5 mL) at -30 °C was added Me2Zn (5.7 mL of a 1.0 M solution
in toluene, 5.70 mmol). The resulting orange mixture was stirred
at that temperature for 10 min. A solution of 24 (450 mg, 2.58
mmol) in CH2Cl2 (2.2 mL) was then added dropwise via cannula.
The dark red reaction mixture was slowly allowed to warm up to
0 °C over a period of about 2 h and was then poured onto ice water.
The aqueous layer was separated from the organic layer and
extracted with Et2O (3 × 20 mL). Combined organic phases were
washed with NaHCO3 (saturated), dried, and concentrated. The
residue was purified by silica gel column chromatography (hexanes
then 10% EtOAc/hexanes) to afford 63 mg of 24 and 376 mg of
25 as a colorless oil (77% yield; 90% yield brsm): IR (neat) νmax
2930, 2869, 1485, 1455 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.15
(d, J ) 8.0 Hz, 1 H), 6.99 (d, J ) 8.0 Hz, 1 H), 2.65 (t, J ) 6.5
Hz, 2 H), 2.26 (s, 3 H), 2.14 (s, 3 H), 1.87-1.81 (m, 2 H),
1.64-1.61 (m, 2 H), 1.29 (s, 6 H); 13C NMR (100 MHz, CDCl3)
δ 143.6 (C), 134.6 (C), 134.5 (C), 133.3 (C), 127.4 (CH), 123.9
(CH), 38.6 (CH2), 33.9 (C), 32.1 (2 × CH3), 28.4 (CH2), 20.5 (CH3),
19.7 (CH2), 15.2 (CH3); HRMS m/z calcd for C14H20 188.1565
(M+), found 188.1563.
ν
max 2929, 2867, 1716, 1650 cm-1; 1H NMR (400 MHz, CDCl3) δ
6.98 (s, 1 H), 5.72 (d, J ) 1.0 Hz, 1 H), 4.14 (q, J ) 7.1 Hz, 2 H),
2.73-2.77 (m, 2 H), 2.61 (t, J ) 6.5 Hz, 2 H), 2.31-2.35 (m, 2
H), 2.22 (d, J ) 1.0 Hz, 3 H), 2.19 (s, 3 H), 2.13 (s, 3 H), 1.77-1.83
(m, 2 H), 1.53-1.60 (m, 2 H), 1.24-1.30 (m, 9 H); 13C NMR
(100 MHz, CDCl3) δ 166.9 (C), 159.6 (C), 143.3 (C), 136.5 (C),
135.1 (C), 132.8 (C), 131.3 (C), 125.0 (CH), 115.7 (CH), 59.5
(CH2), 42.3 (CH2), 38.7 (CH2), 33.8 (C), 32.8 (CH2), 32.0 (2 ×
CH3), 28.5 (CH2), 19.7 (CH2), 19.1 (CH3), 15.7 (CH3), 15.5 (CH3),
14.4 (CH3); HRMS m/z calcd for C22H32O2 328.2402 (M+), found
328.2407.
(E)-3-Methyl-5-(3,4,8,8-tetramethyl-5,6,7,8-tetrahydronaphtha-
len-2-yl)-pent-2-enol (29). A solution of 28 (320 mg, 0.98 mmol)
in CH2Cl2 (9.8 mL) was cooled to -78 °C, and DIBAH (3.0 mL
of a 1.0 M solution in CH2Cl2, 3.00 mmol) was added dropwise
over 5 min. After stirring at -78 °C for 1 h, a 5 M solution (4 mL)
of AcOH in CH2Cl2 was added at -78 °C. The resulting mixture
was then stirred at room temperature, and 25% aqueous sodium
tartrate (5 mL) and H2O (4 mL) were added. The mixture was
extracted with CH2Cl2 (3 × 10 mL). Combined organic phases were
washed with NaHCO3 (saturated) and NaCl (saturated). The organic
layer was dried and concentrated. The residue was purified by silica
gel column chromatography (20% EtOAc/hexanes) to afford 236
mg of 29 as a pale yellow oil (84% yield): IR (neat) νmax 3335
(br), 2927, 2866, 1668 cm-1; 1H NMR (500 MHz, CDCl3) δ 7.00
1,1,5,6-Tetramethyl-7-vinyl-1,2,3,4-tetrahydronaphthalene (26).
Step 1: To a mixture of 25 (479 mg, 2.54 mmol) and iron powder
(28 mg, 0.50 mmol) in 1,2-dichloroethane (20 mL) at 0 °C was
added Br2 (5.60 mL of a 0.50 M solution in CH2Cl2, 2.80 mmol)
dropwise. After stirring for 15 h at rt, cold water was added (10
mL). The aqueous mixture was extracted with Et2O (3 × 20 mL).
Combined organic phases were dried over anhydrous MgSO4. After
filtration and removal of the solvent, the residue was purified by
7438 J. Org. Chem. Vol. 73, No. 18, 2008