A-Ring Functionalization of AdVanced Taxol Precursors
oil: IR (neat, cm-1) 3425, 1732, 1718, 1652; 1H NMR (500 MHz,
C6D6) δ 8.20 (d, J ) 7.6 Hz, 2H), 7.57 (d, J ) 8.4 Hz, 2H), 7.04
(t, J ) 7.2 Hz, 1H), 6.95 (t, J ) 7.8 Hz, 2H), 6.86 (d, J ) 8.5 Hz,
2H), 5.92 (d, J ) 2.1 Hz, 1H), 5.19 (d, J ) 12.8 Hz, 1H), 4.99 (s,
1H), 4.95 (d, J ) 10.5 Hz, 1H), 4.59 (d, J ) 4.4 Hz, 1H), 4.56 (s,
1H), 4.41 (d, J ) 12.6 Hz, 1H), 4.36 (d, J ) 10.5 Hz, 1H), 4.14
(dd, J ) 10.5, 4.5 Hz, 1H), 3.30 (s, 3H), 3.26 (s, 3H), 3.19-3.15
(m, 2H), 2.76 (s, 1H), 1.93 (d, J ) 4.5 Hz, 1H), 1.78-1.73 (m,
1H), 1.65-1.63 (m, 1H), 1.57 (s, 3H), 1.43 (s, 3H), 1.40-1.34
(m, 1H), 1.12 (s, 3H), 0.91 (s, 9H), 0.89-0.86 (m, 1H), 0.02 (s,
3H), 0.00 (s, 3H); 13C NMR (125 MHz, C6D6) δ 208.0, 164.6,
159.9, 158.0, 133.4, 131.3 (2C), 130.4, 130.1 (2C), 129.4 (2C),
129.1 (2C), 128.6, 114.3, 98.9, 86.4, 77.4, 76.5, 74.5, 73.7, 73.1,
60.7, 60.5, 54.9, 54.8, 54.3, 53.8, 40.6, 36.5, 30.7, 29.9, 26.2 (3C),
20.2, 18.6, 11.0, -2.1, -3.6; ES HRMS m/z C41H56O10SiNa (M +
Na)+ calcd 759.3535, obsd 759.3507; [R]20D -43.6 (c 0.32, CHCl3).
Reduction of 23. A solution of 23 (9 mg, 0.01 mmol) and CeCl3‚
H2O (20 mg, 0.054 mmol) in 2 mL of ethanol at 0 °C was treated
with NaBH4 (4 mg, 0.11 mmol), stirred for 3 h, quenched with
saturated NH4Cl solution, diluted with CH2Cl2, and transferred to
a separatory funnel. The aqueous layer was extracted with CH2Cl2
(3 × 10 mL), and the combined organic extracts were washed with
brine, dried, and concentrated under reduced pressure. The resulting
oil was purified by column chromatography on silica gel (5-20%
ethyl acetate/hexanes) to yield 4 mg (50%) of 25 as a clear oil: IR
(film, cm-1) 3378, 1728, 1511; 1H NMR (500 MHz, CDCl3) δ 8.05
(dd, J ) 8.0, 0.91 Hz, 2H), 7.62 (d, J ) 7.5 Hz, 1H), 7.49 (dd, J
) 7.8, 7.5 Hz, 1H), 7.39 (d, J ) 8.6 Hz, 2H), 6.91 (d, J ) 8.6 Hz,
2H), 6.16-6.09 (m, 1H), 5.48-5.41 (m, 3H), 5.30 (dd, J ) 10.4,
1.1 Hz, 1H), 5.03 (d, J ) 1.0 Hz, 1H), 4.81-4.75 (m, 1H), 4.62
(d, J ) 10.6 Hz, 1H), 4.46 (d, J ) 2.1 Hz, 1H), 4.35-4.24 (m,
2H), 4.20 (dd, J ) 7.7, 3.2 Hz, 1H), 3.84 (s, 3H), 3.30 (dd, J )
4.1, 1.8 Hz, 1H), 3.17 (s, 1H), 2.59 (s, 1H), 2.54 (d, J ) 4.3 Hz,
1H), 2.12-1.98 (m, 2H), 1.76-1.64 (m, 1H), 1.28 (s, 3H), 1.26
(s, 3H), 1.21 (s, 3H), 0.91-0.87 (m, 1H), 0.85 (s, 9H), 0.09 (s,
6H); 13C NMR (125 MHz, CDC13) δ 207.8, 164.5, 159.1, 156.3,
152.3, 143.7, 134.2, 133.7, 130.6 (2C), 130.1 (2C), 129.1 (2C),
128.9 (2C), 118.7, 113.9, 113.7, 108.8, 75.5, 72.8, 72.4, 71.3, 68.7,
60.8, 59.3, 55.3, 54.2, 41.6, 36.2, 31.0, 29.7, 25.9 (3C), 22.7, 19.4,
18.2, 14.1, 10.2, -2.5, -4.2; ES HRMS m/z C43H57BrO10SiNa (M
Bromodiosphenol 15. A solution of 4 (107 mg, 0.148 mmol)
and pyridine (24 µL, 0.297 mmol) in 10 mL of CH2Cl2 was cooled
to 0 °C. To the solution was added solid pyr‚HBr3 (47 mg, 0.148
mmol), and the solution was stirred for 1 h, quenched with saturated
NaHCO3 solution, and diluted with CH2Cl2 and H2O. The solution
was transferred to a separatory funnel, and the aqueous layer was
extracted with 3 × 25 mL of CH2Cl2. The combined organic
fractions were washed with brine, dried, and concentrated under
reduced pressure and high vacuum. The resulting yellow oil was
purified by column chromatography on silica gel (5:1 hexanes/ethyl
+ Na)+ calcd 863.2797, obsd 863.2833; [R]21 -9.52 (c 0.42,
D
CHCl3).
O-Acylation of 4 with Allyl Chloroformate. A 10 mL conical
flask was charged with 1 mL of CH2Cl2, allyl chloroformate (10
µL, 0.083 mmol), and DMAP (20 mg, 0.167 mmol). To the cloudy
white solution was added 4 (6 mg, 0.008 mmol) dissolved in 500
µL of CH2Cl2 via cannula, and the reaction mixture was stirred at
room temperature for 2 h, then quenched with saturated NH4Cl
solution. The aqueous layer was extracted with CH2Cl2 (3 × 25
mL), and the combined organic extracts were washed with brine,
dried, and concentrated under reduced pressure to give a yellow
residue that was purified by column chromatography on silica gel
(10:1 to 2:1 hexanes/ethyl acetate) to give 5.3 mg (80%) of 29 as
a colorless oil: IR (neat, cm-1) 3507, 1769, 1727, 1616; 1H NMR
(500 MHz, C6D6) δ 8.20 (d, J ) 7.1 Hz, 2H), 7.46 (d, J ) 8.6 Hz,
2H), 7.10-6.98 (m, 3H), 6.85 (d, J ) 8.7 Hz, 2H), 6.37 (d, J )
6.4 Hz, 1H), 5.92 (d, J ) 5.0 Hz, 1H), 5.67-5.60 (m, 2H), 5.10
(dd, J ) 10.5, 1.1 Hz, 1H), 4.93 (dd, J ) 10.4, 1.1 Hz, 1H), 4.74
(d, J ) 10.2 Hz, 1H), 4.45-4.35 (m, 3H), 4.06 (d, J ) 10.2 Hz,
1H), 3.78 (s, 1H), 3.34 (d, J ) 4.9 Hz, 1H), 3.29 (s, 3H), 3.11 (d,
J ) 1.5 Hz, 1H), 2.92 (d, J ) 4.1 Hz, 1H), 2.17 (d, J ) 4.1 Hz,
1H), 1.91-1.85 (m, 1H), 1.74 (s, 3H), 1.55-1.45 (m, 1H), 1.40-
1.28 (m, 4H), 1.15-1.05 (m, 4H), 0.93 (s, 9H), -0.02 (s, 3H),
-0.03 (s, 3H); 13C NMR (125 MHz, C6D6) δ 207.0, 192.9, 165.1,
160.1, 153.0, 146.1, 139.6, 133.5, 130.4, 130.1, 130.0 (2C), 130.0
(2C), 129.0 (2C), 128.6 (2C), 119.3, 114.3, 83.1, 82.0, 73.8, 73.2,
72.8, 69.7, 65.5, 57.3, 57.0, 54.8, 53.1, 41.5, 41.3, 30.2, 30.0, 29.0,
26.2 (3C), 21.2, 18.5, 1.4, -2.0, -4.0; ES HRMS m/z C44H56O12-
SiNa (M + Na)+ calcd 827.3433, obsd 827.3436; [R]D20 +25.2 (c
0.08, CHCl3).
Phenylselenation of 4. A solution of 4 (200 mg, 0.277 mmol)
in 28 mL of THF was cooled to -78 °C in a 50 mL conical flask.
Lithium hexamethyldisilazide (416 µL of 1.0 M in THF, 0.416
mmol) was added, and the reaction mixture was stirred for 15 min.
Neat phenylselenenyl chloride (79 mg, 0.416 mmol) was added,
and the reaction mixture was stirred for 30 min, quenched with
saturated NH4Cl solution, and transferred to a separatory funnel.
The aqueous layer was extracted with 3 × 25 mL of CH2Cl2, and
the combined organic extracts were dried and concentrated under
reduced pressure. The resulting dark orange residue was purified
by chromatography on silica gel (neat hexanes, then 5:1 hexanes/
ethyl acetate) to give 200 mg (82%) of 33 as a pale orange oil: IR
(film, cm-1) 3420, 1734, 1669; 1H NMR (500 MHz, C6D6) δ 8.15
(d, J ) 7.6 Hz, 2H), 7.49 (dd, J ) 7.6, 1.9 Hz, 2H), 7.32 (d, J )
8.6 Hz, 2H), 7.06 (d, J ) 7.4 Hz, 1H), 7.00 (t, J ) 7.4 Hz, 1H),
acetate) to yield 84 mg (71%) of 15 as a clear oil: IR (neat, cm-1
)
3405, 1731, 1613; 1H NMR (500 MHz, CDCl3) δ 8.08 (d, J ) 7.2
Hz, 2H), 6.95 (d, J ) 8.6 Hz, 2H), 6.75 (s, 1H), 5.49 (d, J ) 2.9
Hz, 1H), 5.02 (d, J ) 0.9 Hz, 1H), 4.68 (d, J ) 7.1 Hz, 1H), 3.87
(s, 3H), 3.72 (d, J ) 4.8 Hz, 1H), 3.41 (s, 1H), 3.58 (s, 1H), 3.00
(d, J ) 4.4 Hz, 1H), 2.37 (d, J ) 4.8 Hz, 1H), 2.12-2.09 (m, 1H),
1.85-1.70 (m, 2H), 1.37 (s, 3H), 1.29 (s, 3H), 1.16 (s, 3H), 0.88
(s, 9H), 0.15 (s, 3H), 0.14 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
207.3, 192.3, 164.7, 148.5, 133.6, 130.1 (2C), 129.8, 129.4 (2C),
129.0, 128.8 (2C), 128.6, 121.3, 113.7 (2C), 82.6, 80.1, 75.3, 72.7,
72.0, 62.7, 58.0, 55.3, 52.7, 42.5, 38.1, 35.0, 30.0, 29.1, 26.0 (3C),
19.6, 18.2, 10.5, -2.4, -4.2; ES HRMS m/z C40H51BrO10SiNa (M
+ Na)+ calcd 821.2327, obsd 821.2376; [R]20 -41.3 (c 0.12,
D
CHCl3).
O-Allylation of 4. A solution of 4 (100 mg, 0.14 mmol) and
K2CO3 (95 mg, 0.69 mmol) in 20 mL of dry DMF was cooled to
0 °C, treated with neat allyl iodide (40 µL, 0.416 mmol), warmed
to room temperature, stirred for 1 h, and treated with 10% aqueous
NaHSO3 solution (∼5 mL) until the solution was clear. The reaction
mixture was diluted with ethyl acetate, transferred to a separatory
funnel, and extracted with the same solvent (3 × 25 mL). The
organic fractions were combined, washed with brine, dried, and
concentrated under reduced pressure, and the resulting oil was
purified by column chromatography on silica gel (5-20% ethyl
acetate in hexanes) to give 80 mg (76%) of 22 as a colorless oil:
IR (neat, cm-1) 1724, 1510, 1248; 1H NMR (500 MHz, CDCl3) δ
8.02 (d, J ) 7.2 Hz, 2H), 7.61 (t, J ) 7.4 Hz, 1H), 7.49 (dd, J )
7.8, 7.7 Hz, 1H), 7.39 (d, J ) 8.5 Hz, 2H), 6.95 (d, J ) 8.6 Hz,
2H), 6.09-6.03 (m, 1H), 5.82 (d, J ) 6.2 Hz, 1H), 5.62 (d, J )
5.4 Hz, 1H), 5.43 (dd, J ) 17.2, 1.2 Hz, 1H), 5.36 (dd, J ) 10.5,
1.0 Hz, 1H), 4.69 (d, J ) 11.0 Hz, 1H), 4.41-4.29 (m, 2H), 4.19-
4.08 (m, 1H), 3.87 (s, 1H), 3.84 (s, 3H), 3.17 (d, J ) 5.3 Hz, 1H),
3.14 (d, J ) 5.7 Hz, 1H), 2.74 (d, J ) 5.7 Hz, 1H), 2.51 (d, J )
3.6 Hz, 1H), 2.20-2.05 (m, 1H), 1.91-1.81 (m, 1H), 1.75-1.70
(m, 1H), 1.64 (s, 3H), 1.13 (s, 3H), 1.09 (s, 3H), 1.08-1.03 (m,
1H), 0.91 (s, 3H), 0.11 (s, 3H), 0.09 (s, 9H), 0.06 (s, 3H); 13C
NMR (125 MHz, CDCl3) δ 208.2, 194.1, 165.1, 159.5, 156.3, 150.5,
143.7, 133.5, 132.1, 129.9 (2C), 129.8 (2C), 129.1 (2C), 128.7 (2C),
120.6, 119.0, 113.9, 84.6, 81.4, 73.5, 72.3, 71.7, 69.6, 57.0, 55.3,
41.7, 41.5, 40.3, 31.9, 31.0, 27.7, 25.9 (3C), 22.7, 21.6, 18.2, 14.1,
12.3, -2.1, -4.1; ES HRMS m/z C43H56O10SiNa (M + Na)+ calcd
783.3535, obsd 783.3517.
J. Org. Chem, Vol. 71, No. 19, 2006 7335