A R T I C L E S
Lautens and Hiebert
MHz, CDCl3) δ 5.72 (ddd, J ) 11.5, 7.5, 2.0 Hz, 1H), 5.36 (dd, J )
11.5, 5.0 Hz, 1H), 4.18 (dd, J ) 4.9, 3.8 Hz, 1H), 3.68 (t, J ) 6.9 Hz,
1H), 2.52 (m, 2H), 2.27 (m, 1H), 1.63 (m, 2H), 1.47 (m, 1H), 1.15 (d,
J ) 7.1 Hz, 3H), 1.13 (d, J ) 7.1 Hz, 3H), 1.08 (m, 21H), 0.97 (t, J
) 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 134.3, 130.7, 76.1,
71.1, 46.0, 42.8, 42.3, 25.7, 18.2, 15.7, 14.3, 12.7, 12.5; HRMS m/z
calcd for C17H33O2Si (M - C3H7)+ 297.2250, found 297.2242.
product. The crude product was purified by flash chromatography on
silica gel (5% Et2O in hexanes) to give the product 30 (57 mg, 84%)
as an oil. The ee was determined to be 98% by HPLC analysis on a
CHIRACEL OD column, λ ) 254 nm, flow rate 0.5 mL/min. Retention
times in 0.2% i-PrOH in hexanes were 11.8 and 12.2 (major) min. IR
(neat) 2942, 2868, 1718, 1459, 1272, 1095, 1066 cm-1; 1H NMR (400
MHz, CDCl3) δ 8.03 (d, J ) 7.0 Hz, 2H), 7.55 (t, J ) 7.4 Hz, 1H),
7.43 (d, J ) 7.6 Hz, 2H), 5.67 (ddd, J ) 11.7, 7.1, 1.5 Hz, 1H), 5.51
(dd, J ) 11.7, 5.5 Hz, 1H), 5.28 (dd, J ) 7.5, 2.2 Hz, 1H), 4.25 (dd,
J ) 4.8, 3.3 Hz, 1H), 2.59 (m, 2H), 2.50 (m, 1H), 1.64 (m, 1H), 1.48
(m, 1H), 1.20 (d, J ) 7.1 Hz, 3H), 1.18 (d, J ) 7.0 Hz, 3H), 1.04 (m,
21H), 0.97 (t, J ) 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 133.2,
132.7, 130.8, 130.3, 129.6, 128.3, 78.1, 72.2, 42.7, 42.2, 41.9, 25.1,
18.2, 16.5, 14.3, 12.8, 12.6; HRMS m/z calcd for C24H37O3Si (M -
C3H7)+ 401.2512, found 401.2508.
(1S,2R,3R,4R,5R,6R,7R)-6-Ethyl-7-iodo-2,4-dimethyl-3-(triiso-
propylsilyl)oxy-8-oxabicyclo[3.2.1]octane (28). A solution of substrate
23 (60 mg, 0.2 mmol), Pd((R)-Tol-BINAP)Cl2 (8.6 mg, 0.01 mmol),
and Zn(OTf)2 (7.2 mg, 0.02 mmol) in CH2Cl2 (4 mL) was stirred at
room temperature for 1 h. To this solution was added Et2Zn (300 µL,
1.0 M in toluene, 0.3 mmol). The resulting mixture was stirred for 4 h
at room temperature. To the reaction was added iodine (126 mg, 0.5
mmol). This was stirred for 6 h at room temperature. The reaction was
then quenched with water. The aqueous layer was extracted with ether
two times. The combined organics were washed with Na2S2O3 solution,
dried with MgSO4, filtered, and evaporated to give crude product. The
crude product was purified by flash chromatography on silica gel (15%
Et2O in hexanes) to give the product 28 (52 mg, 58%) as a white solid.
Mp 91-94 °C; [R]D ) -15.3° (c ) 1.3, CHCl3); IR (neat) 2880, 1460,
(1S,2S,3S,4S,7S)-4-Ethyl-1-(triisopropylsilyl)oxy-2,7-dimethyl-3-
(trimethylsilyl)oxycyclohept-5-ene (31). A solution of substrate 23
(60 mg, 0.2 mmol), Pd((R)-Tol-BINAP)Cl2 (8.6 mg, 0.01 mmol), and
Zn(OTf)2 (7.2 mg, 0.02 mmol) in CH2Cl2 (4 mL) was stirred at room
temperature for 1 h. To this solution was added Et2Zn (300 µL, 1.0 M
in toluene, 0.3 mmol). The resulting mixture was stirred for 4 h at
room temperature. To the reaction was then added (TMS)Cl (64 µL, 1
mmol) at -20 °C, and stirring was continued for 30 min. The reaction
was quenched by addition of water. The aqueous layer was extracted
with ether two times, and the combined organics were dried with
MgSO4, filtered, and evaporated to give crude product. The crude
product was purified by flash chromatography on silica gel (2.5% Et2O
1
1379, 1255, 1020 cm-1; H NMR (400 MHz, CDCl3) δ 5.11 (d, J )
7.9 Hz, 1H), 4.46 (d, J ) 3.5 Hz, 1H), 4.04 (t, J ) 3.8 Hz, 1H), 3.66
(d, J ) 2.8 Hz, 1H), 2.39 (m, 1H), 2.01 (m, 2H), 1.52 (m, 1H), 1.35
(m, 1H), 1.19-1.10 (m, 21H), 1.07 (d, J ) 7.3 Hz, 3H), 0.96 (d, J )
7.3 Hz, 3H), 0.90 (t, J ) 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
91.7, 82.8, 73.9, 42.9, 41.5, 39.5, 35.6, 35.5, 18.6, 18.5, 14.2, 13.8,
13.7, 13.4; HRMS m/z calcd for C17H32O2SiI (M - C3H7)+ 423.1216,
found 423.1214.
in hexanes) to give the product 31 (52 mg, 65%) as an oil. [R]D
)
+110.1° (c ) 0.8, CHCl3); IR (neat) 2944, 1463, 1380, 1253, 1061
cm-1; 1H NMR (400 MHz, CDCl3) δ 5.56 (dd, J ) 11.6, 6.7 Hz, 1H),
5.48 (dd, J ) 11.6, 6.6 Hz, 1H), 4.19 (dd, J ) 5.3, 3.1 Hz, 1H), 3.75
(dd, J ) 7.8, 2.5 Hz, 1H), 2.48 (m, 1H), 2.23 (m, 1H), 2.15 (m, 1H),
1.71 (m, 1H), 1.37 (m, 1H), 1.12 (d, J ) 7.9 Hz, 3H), 1.10 (d, J ) 7.5
Hz, 3H), 1.07 (m, 21H), 0.96 (t, J ) 7.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 133.1, 130.9, 76.3, 72.2, 46.0, 45.2, 42.5, 24.1, 18.3, 18.2,
16.6, 14.9, 13.1, 12.8, 0.4; HRMS m/z calcd for C22H45O2Si2 (M -
CH3)+ 397.2958, found 397.2962.
(1R,2S,3R,4R,5S,6S,7R)-7-Allyl-6-ethyl-2,4-dimethyl-3-(triiso-
propylsilyl)oxy-8-oxabicyclo[3.2.1]octane (29). A solution of substrate
23 (60 mg, 0.2 mmol), Pd((R)-Tol-BINAP)Cl2 (8.6 mg, 0.01 mmol),
and Zn(OTf)2 (7.2 mg, 0.02 mmol) in CH2Cl2 (4 mL) was stirred at
room temperature for 1 h. To this solution was added Et2Zn (300 µL,
1.0 M in toluene, 0.3 mmol). The resulting mixture was stirred for 4 h
at room temperature. The reaction was cooled to -10 °C and a solution
of CuCN‚2LiCl in THF added [made from addition of CuCN (54 mg,
0.6 mmol) to a THF (1 mL) solution of LiCl (50 mg, 1.2 mmol), which
had been dried in vacuo for 2 h at 150 °C]. This was stirred for 10 min
at -10 °C and then allyl bromide (85 µL, 1 mmol) added. This was
stirred at 0 °C for 2 h. The reaction was then quenched with saturated
NH4Cl solution. The aqueous layer was extracted with ether two times.
The combined organics were washed with Na2S2O3 solution, dried with
MgSO4, filtered, and evaporated to give crude product. The crude
product was purified by flash chromatography on silica gel (15% Et2O
2,5-Dimethyl-1,2-dihydronaphthalen-1-ol (33a) and 2,8-Dimethyl-
1,2-dihydronaphthalen-1-ol (33b).26 To a solution of 32 (50 mg, 0.31
mmol) and Pd((S)-t-Bu-POX)Cl2 (8.9 mg, 0.16 mmol) in CH2Cl2 (5
mL) was added Me2Zn (0.31 mL, 2.0 M in toluene). This was stirred
at room temperature for 16 h. The flask was then opened to air, and
several drops of water were added. This solution was stirred for 20
min, allowing for precipitation of zinc salts. MgSO4 was added as a
drying agent followed by filtration and concentration to give the crude
product. The crude product was purified by flash chromatography on
silica gel (15% EtOAc in hexanes) to give the products 33a and 33b
(45 mg, 81%) in a 1:1 ratio. The ee of both isomers was determined to
be 95% using HPLC analysis on a CHIRACEL AD column, λ ) 254
nm, flow rate 0.6 mL/min. Retention times in 2% i-PrOH in hexanes
were 19.3, 25.7 (major), 26.8, and 27.7 (major) min. IR (CHCl3) 3388,
in hexanes) to give the product 29 (49 mg, 64%) as an oil. [R]D
)
-34.4° (c ) 2.4, CHCl3); IR (neat) 2949, 1639, 1458, 1377, 1255,
1
1027 cm-1; H NMR (400 MHz, CDCl3) δ 5.70 (m, 1H), 4.98 (m,
2H), 4.05 (t, J ) 3.9 Hz, 1H), 3.64 (t, J ) 4.1 Hz, 1H), 2.68 (m, 1H),
2.53 (m, 1H), 2.23 (m, 1H), 2.01 (m, 2H), 1.89 (m, 1H), 1.59 (m, 1H),
1.19-1.10 (m, 22H), 0.95 (d, J ) 7.3 Hz, 3H), 0.90 (d, J ) 7.5 Hz,
3H), 0.88 (t, J ) 7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 139.2,
115.4, 84.1, 83.6, 74.2, 42.5, 40.1, 40.0, 39.9, 34.4, 22.5, 18.6, 14.0,
13.8, 13.7, 13.6; HRMS m/z calcd for C20H37O2Si (M - C3H7)+
337.2563, found 337.2568.
1
3022, 2960, 1580, 1471, 1351 cm-1; H NMR (400 MHz, CDCl3) δ
7.24-6.95 (m, 3H), 6.70 (dd, J ) 9.9, 2.6 Hz, 1H), 6.50 (dd, J ) 9.5,
3.1 Hz, 1H), 5.82 (dd, J ) 9.8, 2.9 Hz, 1H), 5.67 (d, J ) 9.5 Hz, 1H),
4.64 (dd, J ) 8.6, 4.4 Hz, 1H), 4.49 (dd, J ) 7.5, 4.8 Hz, 1H), 2.67-
2.53 (m, 2H), 2.43 (s, 3H), 2.34 (s, 3H), 1.64 (d, J ) 7.5 Hz, 1H),
1.40 (d, J ) 7.5 Hz, 1H), 1.37 (d, J ) 7.5 Hz, 3H), 1.23 (d, J ) 7.4
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 136.7, 135.9, 134.5, 133.6,
132.4, 132.1, 131.6, 130.3, 130.2, 129.8, 128.2, 127.2, 127.1, 125.1,
124.7, 123.3, 72.1, 67.1, 35.4, 34.8, 18.9, 18.3, 15.3, 14.1; HRMS m/z
calcd for C12H14O (M)+ 174.1044, found 174.1049.
(1S,2R,3S,4S,7S)-4-Ethyl-1-(triisopropylsilyl)oxy-2,7-dimethyl-
cyclohept-5-en-3-yl Benzoate (30). A solution of substrate 23 (60 mg,
0.2 mmol), Pd((R)-Tol-BINAP)Cl2 (8.6 mg, 0.01 mmol), and Zn(OTf)2
(7.2 mg, 0.02 mmol) in CH2Cl2 (4 mL) was stirred at room temperature
for 1 h. To this solution was added Et2Zn (300 µL, 1.0 M in toluene,
0.3 mmol). The resulting mixture was stirred for 4 h at room
temperature. To the reaction was then added PhCOCl (116 µL, 1 mmol),
and stirring was continued 30 min at room temperature. The reaction
was quenched by addition of DMAP (122 mg, 1 mmol) and then water.
The aqueous layer was extracted with ether two times, and the combined
organics were dried with MgSO4, filtered, and evaporated to give crude
1,3-Diphenylbut-1-enol Trimethylsilyl Ether (41). Dimethylzinc
(215 µL, 2.0 M in toluene, 0.43 mmol) was added to a solution of
substrate 40 (60 mg, 0.29 mmol) and Pd(dppf)Cl2 (11.7 mg, 0.014
(26) Spectral data reported for the mixture.
9
1446 J. AM. CHEM. SOC. VOL. 126, NO. 5, 2004