4768 J . Org. Chem., Vol. 62, No. 14, 1997
Vedejs and Monahan
Rochelle’s salt. The aqueous layer was extracted with Et2O
(40 mL). The combined organic layer was dried (MgSO4) and
filtered. After removal of solvent, the residue (1.71 g) of yellow
oil was purified by flash chromatography on silica gel (5 × 5
cm) 1:1.5 EtOAc/hexane eluent, fractions of 5 mL after an
initial fraction of 100 mL. Fractions 2-5 contained 163 mg
of recovered ester 16. Fractions 14-28 contained 1.47 g (6.82
mmol, 86%) of 3-(2′-phenyloxazol-5-yl)but-2-enol (18) (6.1:1,
Z:E), sufficiently pure for the next step. For analytical
purposes, 64 mg of the product was repurified by preparative
layer chromatography on silica gel (20 × 20 × 0.1 cm), 1:4
THF/hexane eluent; to afford 42 mg of the Z isomer as the
leading zone. (Z)-3-(2′-phenyloxazol-5′-yl)but-2-enol (18): ana-
lytical TLC on silica gel, 1:4 THF/hexane, Rf ) 0.13; molecular
ion calcd for C13H13NO2 215.094 64, found m/ e 215.0945, error
) 1 ppm; base peak ) 172 amu; IR (CCl4, cm-1) 3347, OH;
300 MHz NMR (CDCl3, ppm) δ 8.04-8.00 (2H, m) 7.49-7.44
(3H, m) 7.10 (1H, s) 5.76-5.72 (1H, m) 4.65-4.61 (2H, m)
2.10-2.09 (3H, m) 1.91 (1H, t, J ) 5.8 Hz). 13C NMR (75.4
MHz, CDCl3, ppm) δ 161.2, 150.9, 130.5, 129.6, 128.8, 127.0,
126.5, 126.2, 122.6, 60.3, 20.6.
tions 15-30 contained 1.29 g of the Z enynol 21 contaminated
by another substance, tentatively believed to result from
conjugate addition of propiolate to 21 (10:1 by 1H NMR, 88%
combined yield). This material was sufficiently pure for the
next step. An analytical sample was obtained from a 38 mg
of the sample by preparative layer chromatography on silica
gel (20 × 20 × 0.1 cm), 1:4 THF/hexane eluent, to yield 32 mg
of pure Z enynol 21: analytical TLC on silica gel, 1:4 THF/
hexane, Rf ) 0.15; molecular ion calcd for C18H17NO4:
311.115 72, found m/ e 311.1143, error ) 5 ppm; base peak )
105 amu; IR (CCl4, cm-1) 1718, CdO; 300 MHz NMR (CDCl3,
ppm) δ 8.04-8.01 (2H, m) 7.47-7.43 (3H, m) 7.22 (1H, s) 5.74
(1H, d, J ) 8.2 Hz) 5.56 (1H, dq, J ) 8.2, 1.2 Hz) 4.20 (2H, q,
J ) 7.0 Hz) 3.0-2.6 (1H, br) 2.09 (3H, d, J ) 1.2 Hz) 1.26 (3H,
t, J ) 7.0 Hz); 13C NMR (75.4 MHz, CDCl3, ppm) δ 161.9, 153.2,
149.7, 130.8, 128.9, 128.0, 126.8, 126.5, 126.0, 125.6, 86.0, 76.4,
62.2, 59.3, 20.7, 14.0.
Eth yl (Z)-4-(ter t-Bu tyld im eth ylsiloxy)-6-(2′-p h en ylox-
a zol-5′-yl)h ep t-5-en -3-yn oa te (8). To 260 mg (0. 830 mmol)
of the contaminated alcohol 21 from above in 4 mL of CH2Cl2
was added tert-butyldimethylchlorosilane (163 mg, 1.09 mmol,
Aldrich) followed immediately by imidazole (73 mg, 1.09 mmol,
Aldrich). Within 1 min, the reaction had turned cloudy in
appearance. After 12 h, the mixture was filtered through a 1
in. plug of Celite. After removal of solvent (aspirator), the
residue was purified by flash chromatography on silica gel (12
× 2 cm), 1:2:17 EtOAc/dichloromethane/hexane eluent, frac-
tions of 5 mL after an initial fraction of 75 mL. Fractions 5-25
contained 241 mg (68%) of the (Z)-tert-butyldimethylsilyl-
protected alkynyl alcohol 8. The contaminants (tentatively,
derived from the conjugate addition product from the propi-
olate step and from the E-isomer of 8) eluted in later fractions,
but were not obtained pure . Analytical data for 8: TLC on
silica gel, 1:9 EtOAc/hexane, Rf ) 0.17; molecular ion calcd
for C24H31NO4Si 425.202 21, found m/ e 425.2016, error ) 1
ppm; base peak ) 105 amu; IR(CCl4, cm-1) 1709, CdO; 300
MHz NMR (CD2Cl2, ppm) δ 8.09-8.05 (2H, m) 7.51-7.48 (3H,
m) 7.22 (1H, s) 5.80 (1H, d, J ) 7.9 Hz) 5.60 (1H, dq, J ) 7.9,
1.1 Hz) 4.18 (2H, q, J ) 7.2 Hz) 2.13-2.12 (3H, m) 1.25 (3H,
t, J ) 7.2 Hz) 0.91 (9H, s) 0.14 (3H, s) 0.12 (3H, s); 13C NMR
(75.4 MHz, CD2Cl2, ppm) δ 162.1, 153.7, 150.4, 131.0, 129.3,
128.3, 128.2, 127.6, 126.8, 123.9, 86.8, 76.2, 62.4, 60.9, 25.8,
20.8, 18/5, 14.2, -4.5, -4.6.
(Z)-3-(2′-P h en yloxa zol-5′-yl)bu t-2-en a l (20). To a mix-
ture of butenols 18 (6.1:1, Z:E; 1.41 g, 6.54 mmol) in 20 mL of
CH2Cl2 was added 3.72 g of 4 Å powdered molecular sieves
and N-methylmorpholine N-oxide (1.15 g, 9.81 mmol, Aldrich).
The mixture was cooled to 0 °C, and tetrapropylammonium
perruthenate12 (TPAP, 103 mg, 0.327 mmol, Aldrich) was
added in portions. TLC analysis after 2 h showed that starting
material was still present. An additional portion of TPAP (20
mg, 0.0634 mmol) was added, and the reaction was stirred for
an additional 30 min. The solution was filtered through a 2
in. plug of celite and a 0.5 in. layer of silica gel with CH2Cl2.
After removal of solvent (aspirator), the residue (1.37 g) was
purified by flash chromatography on silica gel (7.5 × 5 cm),
1:2:7 EtOAc/dichloromethane/hexane eluent, fractions of 5 mL
after an initial fraction of 50 mL. Fractions 22-35 contained
1.03 g (73%) of an 8:1 Z:E mixture of aldehyde 20. Fractions
36-42 contained an additional 47 mg of the E aldehyde. A
27 mg portion of material was repurified by preparative layer
chromatography on silica gel (20 × 20 × 0.1 cm), 1:4 THF/
hexane eluent to yield 22 mg of Z aldehyde 20: analytical TLC
on silica gel, 1:4 THF/hexane, Rf ) 0.32. Pure material was
obtained by crystallization from hexane: mp 114.5-115.5 °C;
white needles; molecular ion calcd for C13H11NO2 213.078 98,
found m/ e 213.0767, error ) 10 ppm; base peak ) 110 amu;
IR (CCl4, cm-1) 1670, CdO; 300 MHz NMR (CDCl3, ppm) δ
10.52 (1H, d, J ) 8.3 Hz) 8.06-8.02 (2H, m) 7.51-7.45 (4H,
Ben zyltr im eth yla m m on iu m Cya n id e.17 A small varia-
tion of the literature method was used as follows. Benzyltri-
methylammonium methoxide (17.9 g, 40 wt %, Aldrich) was
diluted with 25 mL of methanol. Gaseous HCl was added to
the solution at 0 °C. After 30 min the solution was concen-
trated and the resulting residue crystallized twice from
acetonitrile. The resulting white plates were collected by
removing the solvent by cannula and dried in the presence of
P2O5 under vacuum for 3 days to afford 5.33 g (73%) of the
chloride salt as a hygroscopic white solid. Benzyltrimethyl-
ammonium chloride (2.75 g, 14.8 mmol) was dissolved in 25
mL of methanol. The solution was added to a solution of
NaCN in 80 mL of methanol via cannula and rinsed with an
additional 8 mL portion of methanol. The resulting mixture
turned cloudy rapidly. After 1.5 h, the solution was filtered
through a 10 cm plug of Celite and concentrated. The residue
was crystallized from acetonitrile and the solvent removed by
cannula. The resulting white plates were dried with a N2
stream and then in a vacuum desiccator over P2O5 for 3 d to
afford 1.71 g (66%) of benzyltrimethylammonium cyanide as
a hygroscopic white solid.
Yellow Qu in on e 10: 1-Meth yl-2-p h en yl-3-ca r beth oxy-
6-m eth yl-4,7-in d oloqu in on e. Oxazole 8 (290 mg, 0.680
mmol) was dried by azeotropic distillation with benzene (1 ×
10 mL), and 150 mg of powdered 3Å molecular sieves was
added followed by 7 mL of acetonitrile. The mixture was
stirred for 10 min followed by the addition of methyl triflate
(96 µL, 0.849 mmol, Aldrich) and stirring for 10 h at room
temperature. TLC analysis indicated a small amount of
unreacted oxazole 8 present. An additional portion of methyl
triflate (20 µL, 0.177 mmol) was added and the reaction stirred
24 h more at room temperature. Stirring was discontinued,
and the solution was transferred by cannula away from the
m) 5.97 (1H, dd, J ) 8.3, 1.1 Hz) 2.29 (3H, d, J ) 1.1 Hz); 13
C
NMR (75.4 MHz, CDCl3, ppm) δ 192.2, 163.9, 149.6, 139.6,
131.9, 131.4, 129.0, 128.0, 126.9, 126.3, 21.6.
E t h yl (Z)-4-H yd r oxy-6-(2′-p h en yloxa zol-5′-yl)h ep t -5-
en -3-yn oa te (21). To CeCl3 (2.89 g, 11.7 mmol, Aldrich, dried
4 h at 135 °C/0.5 torr) was added 60 mL of THF, and the
mixture was stirred of 24 h. In a separate flask, HMDS (1.98
mL, 9.38 mmol, Aldrich, distilled) was added to 45 mL of THF.
The mixture was cooled to -78 °C. n-BuLi (5.90 mL, 1.63 M
in hexane, Aldrich) was added, and the solution was stirred
for 45 min and added via cannula (5 min) to the CeCl3 solution
to which ethyl propiolate (0.95 mL, 9.38 mmol, Lancaster
Synthesis, distilled) had been added. The resulting deep rust-
colored solution was stirred at -78 °C for 1.5 h. In a separate
flask, the aldehyde 20 (1.00 g, 4.69 mmol, 8:1 Z:E, azeotropi-
cally dried with 2 × 20 mL portions of benzene) was dissolved
in 5 mL of THF. The solution was cooled to -78 °C and added
dropwise via cannula to the CeCl3 solution. After 2 h, the
cooling bath was removed, and saturated NH4Cl (15 mL) was
added. The solution was extracted with Et2O (3 × 40 mL, with
additions of brine and hexane to break emulsions). The
combined organic layer was dried (MgSO4) and concentrated
to give 1.63 g of yellow oil. The residue was purified by flash
column chromatography on silica gel (15 × 4 cm) 1:2.3 EtOAc/
hexane eluent, fractions of 5 mL after an initial fraction of
150 mL. Fractions 1-4 contained 39 mg of the trimethylsilyl-
protected alkynyl alcohol. Fractions 7-12 contained 25 mg
of a mixture of compounds containing unreacted starting
material, oxazole alcohol 18, and unidentified products. Frac-