distilled over KOH. CuI12 was purified by known methods.
Phosgene was purchased as a 1.93 M solution in toluene from
Fluka Chemical Corp. and used as supplied. Pd(PPh3)4 was
synthesized13 by a known method. Peroxotungstophosphate
(PCWP) was freshly prepared according to the known proce-
dure.14 All other reagents were used as supplied. All reactions
were carried out in oven-dried glassware under argon pressure
unless otherwise specified. Analytical thin-layer chromatography
was performed on Sorbent Technologies 0.20 mm silica gel 60 Å
plates. Flash chromatography was performed on Sorbent Tech-
nologies 32-63 µm 60 Å silica gel.15
ter t-Bu tylp en t-4-en yloxyd ip h en ylsila n e. An oven-dried
100 mL flask was charged with 4-penten-1-ol (6) (1.00 g, 11.61
mmol) and a magnetic stir bar. The alcohol was dissolved in 30
mL of DMF. To the reaction mixture were then added imidazole
(1.58 g, 23.22 mmol) and TBDPSCl (3.09 g, 11.26 mmol). The
reaction mixture was stirred at rt for 12 h, diluted with water
(50 mL), and extracted with Et2O (3 × 50 mL). The combined
organic extracts were washed with water (100 mL) and brine
(100 mL), dried with MgSO4, filtered, and concentrated in vacuo.
The residue was purified on SiO2 (2% EtOAc/hexanes) to give
3.76 g (99%) of silyl ether as a colorless oil: 1H NMR (400 MHz,
CDCl3) δ 7.66-7.63 (m, 4H), 7.42-7.32 (m, 6H), 5.78 (ddt, 1H,
J ) 7.2, 10.2, 15.6 Hz), 4.98 (dd, 1H, J ) 1.4, 15.6 Hz), 4.90 (dd,
1H, J ) 1.4, 10.2 Hz), 3.65 (t, 2H, J ) 6.4 Hz), 2.13 (dt, 2H, J )
7.2, 7.6 Hz), 1.64 (tt, 2H, J ) 6.4, 7.6 Hz), 1.03 (s, 9H); 13C NMR
(75 MHz, CDCl3) δ 138.5, 135.6, 134.1, 129.5, 127.6, 114.5, 63.3,
31.8, 30.0, 26.9, 19.2; IR (neat) νmax 3071, 2956, 2932, 2858, 2361,
2383, 1640, 1472, 1428, 1109, 703; HRMS (CI, CH4) m/z calcd
for C21H29OSi [M + H]+ 325.1987, found 325.1968.
5-(ter t-Bu tyld ip h en ylsila n yloxy)p en ta n e-1,2-d iol (7). A
250 mL round-bottom flask was charged with the silyl ether of
6 and a stir bar and diluted with 60 mL of acetone/water (10:1).
Trimethylamine N-oxide (1.93 g, 17.42 mmol) was then added
to the reaction mixture. A 0.2 M solution of OsO4 in toluene was
added (1.16 mL, 0.232 mmol), and the reaction mixture was
stirred overnight at rt. The reaction was quenched by the
addition of saturated sodium sulfite (100 mL) and extracted with
EtOAc (3 × 150 mL). The combined organic layers were washed
with brine, dried with MgSO4, filtered, and concentrated in
vacuo. The residue was purified on SiO2 (50% EtOAc/Hexanes)
to give 3.86 g of 7 (95%) as a colorless oil: 1H NMR (400 MHz,
CDCl3) δ 7.66-7.63 (m, 4H), 7.42-7.32 (m, 6H), 3.77-3.71 (m,
1H), 3.68 (t, 2H, J ) 5.6 Hz); 3.64 (dd, 1H, J ) 3.2, 8.0 Hz); 3.45
(dd, 1H, J ) 3.2, 7.6 Hz); 1.67-1.46 (m, 4H), 1.03 (s, 9H); 13C
NMR (75 MHz, CDCl3) δ 135.5, 133.5, 129.6, 127.6, 71.9, 66.7,
63.9, 29.9, 28.6, 26.8, 19.1; IR (neat) νmax 3398, 3071, 2932, 2859,
1710, 1427, 1109, 735; HRMS(CI, NH3) m/z calcd for C22H31O3-
Si [M + H]+ 359.2042, found 359.2072.
5-(ter t-Bu t yld ip h en ylsila n yloxy)-1-h yd r oxyp en t a n -2-
on e (8). A 100 mL round-bottom flask was charged with diol 7,
a stir bar, and diluted with 15 mL of CHCl3. PCWP (0.111 g,
0.053 mmol) and 30% H2O2 (1.64 mL, 16.02 mmol) were added
to the reaction mixture. The flask was fitted with a reflux
condenser and refluxed for 16 h with stirring before heating was
discontinued. The reaction was quenched by the addition of
saturated sodium sulfite (15 mL) and water (30 mL). The organic
layer was separated, and the remaining aqueous layer was
extracted with EtOAc (2 × 50 mL). The combined organic layers
were dried with MgSO4, filtered, and concentrated in vacuo. The
residue was purified on SiO2 (30% EtOAc/hexanes) to give 0.903
g of 8 (95%) as a pale yellow oil: 1H NMR (400 MHz, CDCl3) δ
7.63-7.60 (m, 4H), 7.43-7.35 (m, 6H), 4.22 (d, 2H, J ) 4.8 Hz),
3.66 (t, 2H, J ) 6.0 Hz), 3.04 (t, 1H, J ) 4.8 Hz), 2.51 (t, 2H, J
) 7.6 Hz), 1.86 (tt, 2H, J ) 6.0, 7.6), 1.02 (s, 9H); 13C NMR (75
MHz, CDCl3) δ 209.4, 135.5, 133.4, 129.6, 127.6, 67.9, 62.7, 34.7,
26.7, 26.2, 19.0; IR (neat) νmax 3485, 3072, 2932, 2859, 2252,
1719, 1428, 1109, 909; HRMS(CI, CH4) m/z calcd for C21H29O3-
Si [M + H]+ 357.1886, found 357.1930.
4-[3-(ter t-Bu tyld ip h en ylsila n yloxy)p r op yl]-3H-oxa zol-2-
on e (9). A 100 mL round-bottom flask was charged with ketone
8 (0.570 g, 1.60 mmol) and a stir bar. Benzene (3 mL) and N,N-
dimethylaniline (0.50 mL) were added, and the reaction mixture
was cooled to 0 °C. Phosgene (0.950 mL, 1.93 M in toluene, 1.83
mmol) was added, and the reaction mixture was stirred for 30
min. Concentrated NH4OH (10 mL) was added carefully with a
pipet, and the reaction mixture was stirred for an additional 30
min before concd H2SO4 was added to bring the reaction pH to
approximately 3. The reaction mixture was diluted with water
(100 mL) and extracted with EtOAc (3 × 50 mL). The combined
organic layers were washed with brine, dried with MgSO4,
filtered, and concentrated in vacuo. The residue was purified
on SiO2 (40% EtOAc/hexanes) to give 0.519 g of 9 (85%) as a
yellow oil: 1H NMR (400 MHz, CDCl3) δ 8.54 (bs, 1H), 7.64-
7.61 (m, 4H), 7.43-7.37 (m, 6H), 6.42 (s, 1H), 3.69 (t, 2H, J )
5.6 Hz), 2.45 (t, 2H, J ) 7.6 Hz), 1.74 (tt, 2H, J ) 5.6, 7.6 Hz),
1.05 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 158.1, 135.4, 133.5,
129.6, 127.6, 127.1, 124.1, 62.3, 29.5, 26.8, 20.4, 19.1; IR (neat)
νmax 3163, 3071, 2932, 2858, 1746, 1472, 1109, 704; HRMS(CI,
NH3) m/z calcd for C23H28NO3Si [M + H]+ 382.1838, found
382.1840.
Tr iflu or om eth a n esu lfon ic Acid 4-[3-(ter t-Bu tyld ip h en -
ylsila n yloxy)p r op yl]oxa zol-2-yl Ester (4). A 100 mL round-
bottom flask was charged with oxazolone 9 (0.250 g, 0.655 mmol)
and a stir bar. CH2Cl2 (3.5 mL) was added, and the reaction
mixture was cooled to -78 °C. 2,6-Lutidine (0.140 g, 1.31 mmol)
was then added via syringe followed by the addition of Tf2O
(0.277 g, 0.983 mmol). The reaction mixture was then allowed
to warm to rt with stirring for 30 min. The reaction was diluted
with water (50 mL) and extracted with CH2Cl2 (3 × 50 mL).
The combined organic layers were washed with brine, dried with
MgSO4, filtered, and concentrated in vacuo. The residue was
purified on SiO2 (10% Et2O/pentane) to give 0.280 g of 4 (80%)
as a colorless oil. Triflate 4 is chemically unstable and used
immediately after preparation: 1H NMR (400 MHz, CDCl3) δ
7.64-7.60 (m, 4H), 7.41-7.34 (m, 6H), 7.12 (s, 1H), 3.67 (t, 2H,
J ) 6.0 Hz), 2.61 (t, 2H, J ) 7.6 Hz), 1.85 (tt, 2H, J ) 6.0, 7.6
Hz), 1.03 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 149.5, 142.1,
135.5, 133.9, 133.7, 129.6, 127.7, 118.4 (q, CF3, J ) 319.7 Hz),
62.5, 30.3, 26.8, 22.9, 19.2; IR (neat) νmax 2932, 2361, 1735, 1426,
1248, 1030, 702; HRMS (CI, CH4) m/z calcd for C23H26F3NO5-
SSi [M]+ 513.1253, found 513.1282.
[3-[4-[3-(ter t-Bu tyld ip h en ylsila n yloxy)p r op yl]oxa zol-2-
yl]p r op -2-yn yl]ca r ba m ic Acid Meth yl Ester (12). A 50 mL
round-bottom flask was charged with triflate 4 (0.130 g, 0.253
mmol) and a stir bar. 1,4-Dioxane (1.2 mL) and 2,6-lutidine
(0.136 g, 1.23 mmol) were added with stirring. Alkyne 11 (0.045
g, 0.405 mmol), Pd(PPh3)4 (30 mg, 0.025 mmol), and CuI (3 mg,
0.013 mmol) were added, and the reaction mixture was stirred
at rt for 4-5 h. The reaction mixture was then diluted with
EtOAc (∼10 mL) and filtered through a thin pad of SiO2 and
concd in vacuo. The residue was purified on SiO2 (30% EtOAc/
hexanes) to give 0.101 g of 12 (84%) as a colorless oil: 1H NMR
(400 MHz, CDCl3) δ 7.64-7.62 (m, 4H), 7.41-7.32 (m, 6H), 7.21
(s, 1H), 4.90 (bs, 1H), 4.22-4.19 (m, 2H), 3.69 (bs, 3H), 3.66 (t,
2H, J ) 6.4 Hz), 2.61 (t, 2H, J ) 7.6 Hz), 1.87 (tt, 2H, J ) 6.4,
7.6 Hz), 1.03 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 156.5, 145.5,
141.7, 135.5, 135.1, 133.7, 129.5, 127.6, 87.9, 71.3, 62.7, 52.5,
31.2, 30.8, 26.8, 22.4, 19.1; IR (neat) νmax 3542, 3072, 2956, 2931,
2859, 2252, 1724, 1515, 1253, 1110, 734; HRMS (CI, CH4) m/z
calcd for C28H33N2O4Si [M + H]+ 477.2209, found 477.2208.
[3-[4-[3-(ter t-Bu tyld ip h en ylsila n yloxy)p r op yl]oxa zol-2-
yl]p r op -2-yn yl]ca r ba m ic Acid Meth yl Ester (13). A 50 mL
round-bottom flask was charged with oxazole 12 (0.101 g, 0.210
mmol) and a stir bar. EtOAc (23.0 mL) and quinoline (0.043 g,
0.336 mmol) were added with stirring. Lindlar’s catalyst, 5 wt
% Pd on CaCO3 posioned w/lead (0.101 g, 100 wt %), was added,
and the reaction was placed under H2 and stirred for 3 h. The
reaction was filtered through a pad of Celite and concentrated
(12) Organocopper Reagents. A Practical Approach; Taylor, R. J . K.,
Ed.; Oxford University Press: Oxford, 1994; pp 39-41.
(13) Hegedus, L. S. In Organometallics in Synthesis: A Manual;
Schlosser, M., Ed.; J ohn Wiley & Sons Ltd.: New York, 1994; Chapter
5, p 448.
(14) Ishii, Y.; Yamawaki, K.; Ura, T.; Yamada, H.; Yoshida, T.;
Ogawa, M. J . Org. Chem. 1988, 53, 3587-3593.
(15) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923-
2925.
6814 J . Org. Chem., Vol. 67, No. 19, 2002