Stereoselective Synthesis of Cyclic Ethers
A mixture of the allylic alcohol (5.5 g, 20.2 mmol) and PtO2
(20 mg) in MeOH (125 mL) was placed under a H2 atmosphere.
The reaction mixture was vigorously stirred until TLC showed
complete conversion. The mixture was filtered through What-
man paper no. 4. The solvent was removed under reduced
pressure and the residue was purified by silica gel column
NMR (CDCl3) δ 0.06 (s, 12H), 0.88 (s, 18H), 1.43 (m, 2H), 1.61
(m, 8H), 1.82 (m, 2H), 2.02 (m, 4H), 3.08 (m, 2H), 3.34 (m,
4H), 3.74 (m, 1H), 3.79 (m, 1H), 3.89 (d, J ) 11.1 Hz, 2H),
4.05 (m, 1H), 4.09 (m, 3H), 4.17 (m, 1H), 4.24 (dd, J ) 6.0, 6.0
Hz, 1H), 5.80 (s, 1H), 5.94 (s, 1H), 7.37 (m, 6H), 7.48 (m, 4H);
13C NMR (CDCl3) δ -4.7 (q), -3.9 (q), 17.9 (s), 25.5 (t), 25.7
(q), 27.6 (t), 27.6 (t), 29.4 (t), 29.5 (t), 33.5 (t), 67.3 (t), 67.6 (t),
67.8 (t), 70.4 (d), 70.5 (d), 71.8 (d), 71.9 (d), 78.7 (d), 79.2 (d),
82.8 (d), 82.9 (d), 103.9 (d), 104.1 (d), 126.4 (d), 126.6 (d), 128.3
(d), 128.4 (d), 129.1 (d), 129.3 (d), 137.4 (s), 138.2 (s); IR (CHCl3)
(cm-1) 3364, 2930, 1461, 1255, 1094; MS m/z (rel intensity)
422 (M)+ (4), 273 (28), 259 (17), 167 (40), 149 (21), 141 (55),
105 (77), 97 (100). Anal. Calcd for C23H38O5Si: C, 65.36; H,
9.06. Found: C, 65.34; H, 9.18.
To a stirred suspension of NaH (60% in mineral oil, 63 mg,
1.56 mmol) in dry THF (10 mL) at 0 °C were sequentially and
slowly added a solution of the alcohol benzylidene (550 mg,
1.3 mmol) in THF (3 mL), a catalytic amount of Bu4NI, and
benzyl bromide (0.22 mL, 1.82 mmol). The reaction mixture
was stirred at room temperature for 24 h. Then, the mixture
was diluted with Et2O, washed with brine, dried, and concen-
trated.
To a stirred mixture of the crude product in MeOH (13 mL)
was added concentrated HCl until pH ∼1 at room temperature.
The reaction mixture was stirred at room temperature until
TLC showed completion of the reaction (ca. 5 min), whereupon
it was quenched with Et3N until pH ∼7. The reaction mixture
was stirred for 5 min and concentrated under reduced pres-
sure, and the crude residue obtained was purified by silica gel
column chromatography to yield 28 (442 mg, 80% overall yield)
as a colorless oil: [R]25D +53.9 (c 0.6, CHCl3); 1H NMR (CDCl3)
δ 0.05 (s, 3H), 0.06 (s, 3H), 0.87 (s, 9H), 1.37 (m, 1H), 1.45 (m,
1H), 1.64 (m, 2H), 1.69 (m, 1H), 1.76 (m,1H), 1.99 (dd, J )
12.2, 2.5 Hz, 1H), 2.07 (m, 1H), 2.46 (br s, 1H), 2.88 (br s, 1H),
3.01 (ddd, J ) 8.8, 8.8, 1.7 Hz, 1H), 3.28 (m, 2H), 3.56 (m,
1H), 3.73 (m, 3H), 3.87 (dd, J ) 10.1, 1.6 Hz, 1H), 4.54 (d, J )
11.4 Hz, 1H), 4.64 (d, J ) 11.4 Hz, 1H), 7.29 (m, 1H), 7.32 (m,
4H); 13C NMR (CDCl3) δ -4.6 (q), -4.0 (q), 17.9 (s), 25.7 (t),
25.8 (q), 26.1 (t), 27.9 (t), 33.6 (t), 63.4 (t), 67.8 (t), 71.4 (d),
72.5 (d), 81.5 (d), 82.8 (d), 127.7 (d), 127.8 (d), 128.4 (d), 138.2
(s); IR (CHCl3) (cm-1) 3565, 3470, 2931, 2858, 1211, 1092; MS
m/z (rel intensity) 367 (M - 57)+ (1), 363 (3), 259 (4), 171 (3),
101 (10), 91 (100). Anal. Calcd for C23H40O5Si: C, 65.05; H,
9.49. Found: C, 65.05; H, 9.79.
P r ep a r a tion of ter t-Bu tyl(d im eth yl){[(2R,3S)-2-(4-p en -
ten -1-yn yl)tetr a h yd r o-2H-p yr a n -3-yl]oxy}sila n e (34). To
a stirred solution of the alkyne 3318 (1.3 g, 5.4 mmol) in dry
DMF (18 mL) under argon were sequentially added K2CO3
(1.06 g, 7.6 mmol), tetrabutylammonium bromide (227 mg, 0.7
mmol), and copper(I) iodine (52 mg, 0.27 mmol) at room
temperature. After 10 min, allyl bromide (0.61 mL, 7.04 mmol)
was added. The reaction mixture was stirred for 60 h. Then it
was poured into H2O and extracted with ether. The combined
organic phases were washed with brine, dried, and concen-
trated. The crude obtained was purified by silica gel flash
chromatography to afford quantitatively 26 (5.53 g) as an oil:
1
[R]25 + 51.0 (c 3.1, CHCl3); H NMR (CDCl3) δ 0.42 (s, 6H),
D
0.86 (s, 9H), 1.39 (m, 2H), 1.65 (m, 4H), 2.00 (m, 2H), 2.83 (br
s, 2H), 3.01 (ddd, J ) 8.7, 8.7, 2.2 Hz, 1H), 3.30 (m, 2H), 3.59
(m, 2H), 3.87 (m, 1H); 13C NMR (CDCl3) δ -4.8 (q), -4.1 (q),
17.8 (s), 25.5 (t), 25.7 (q), 29.0 (t), 29.1 (t), 33.5 (t), 62.9 (t),
67.7 (t), 70.9 (d), 82.8 (d); IR (CHCl3) (cm-1) 3398, 3006, 2955,
2858, 1463, 1257; MS m/z (rel intensity) 217 (M - 57)+ (3),
205 (10), 199 (100). Anal. Calcd for C14H30O3Si: C, 61.26; H,
11.02. Found: C, 61.27; H, 11.12.
P r ep a r a tion of Ben zoic Acid (1S,2R)-1-{2-[(2R,3S)-3-
(ter t-Bu tyld im eth ylsila n yloxy)tetr a h yd r op yr a n -2-yl]eth -
yl}-2,3-d ih yd r oxyp r op yl Ester (28). Crushed, activated 4
Å molecular sieves (20% w) were added to stirred CH2Cl2 (125
mL) under argon. The flask was cooled to -20 °C and Ti(OPr-
i)4 (0.4 mL, 1.3 mmol), (S,S)-(-)-diethyl tartrate (0.27 mL, 1.6
mmol), and the allylic alcohol 27 (4 g, 13.3 mmol) in CH2Cl2
(8 mL) were added sequentially with stirring. The mixture was
stirred for 15 min, and tert-butyl hydroperoxide (5.3 mL, 4.5
M in isooctane, 23.9 mmol) was added slowly. After the
addition, the reaction was maintained with stirring overnight.
The reaction was allowed to reach room temperature, and
benzoic acid (2.92 g, 23.9 mmol) was added. The mixture was
additionally stirred for 15 min, and Ti(OPr-i)4 (4.75 mL, 16
mmol) was added. Then, the mixture was allowed to warm to
room temperature and the solution was stirred for 2 h. Tartaric
acid aqueous solution (15% w/v, 125 mL) was added, and
stirring was continued until clear phases were reached (30
min). The layers were separated, and the aqueous phase was
extracted with CH2Cl2. The combined organic phases were
washed with a saturated aqueous solution of NaHCO3 and
brine, dried, concentrated, and purified by silica gel column
chromatography, to yield the diol benzoate (4.1 g, 71% overall
1
yield) as an oil: [R]25 +21.6 (c 2.1, CHCl3); H NMR (CDCl3)
D
δ -0.1 (s, 3H), -0.01 (3H), 0.73 (s, 9H), 1.37 (m, 2H), 1.62 (m,
2H), 1.79 (m, 1H), 1.96 (m, 1H), 2.04 (m, 1H), 2.16 (m, 1H),
2.6 (br s, 1H), 2.94 (br s, 1H), 2.91 (ddd, J ) 9.0, 9.0, 2.4 Hz,
1H), 3.26 (m, 1H), 3.62 (dd, J ) 11.8, 5.4 Hz, 1H), 3.72 (m,
1H), 3.86 (m, 1H), 5.1 (m, 1H), 7.43 (dd, J ) 8.0, 8.0 Hz, 2H),
7.56 (dd, J ) 7.6, 7.6 Hz, 1H), 8.03 (d, J ) 7.2 Hz, 2H); 13C
NMR (CDCl3) δ -4.9 (q), -4.0 (q), 17.8 (s), 25.6 (q), 25.8 (t),
27.0 (t), 28.3 (t), 33.6 (t), 62.6 (t), 67.8 (t), 71.2 (d), 73.3 (d),
75.4 (d), 82.7 (d), 128.4 (d), 129.7 (s), 129.8 (d), 133.3 (d), 167.1
(s); IR (CHCl3) (cm-1) 3459, 2930, 2857, 1713, 1211; MS m/z
(rel intensity) 381 (M - 57) (11), 259 (15), 199 (6), 122 (24),
105 (100). Anal. Calcd for C23H38O6Si: C, 62.98; H, 8.73.
Found: C, 62.66; H, 8.99.
To a stirred solution of diol benzoate (4 g, 9.1 mmol) in dry
CH2Cl2 (91 mL) were sequentially added a catalytic amount
of CSA (100 mg, 0.46 mmol) and benzaldehydedimethyl acetal
(2.05 mL, 13.7 mmol) at room temperature. The reaction
mixture was stirred for 2 h, after which time TLC showed
complete conversion to the benzylidene derivative. Then, Et3N
was added until pH ∼7, and the mixture was stirred for 5 min
and evaporated under reduced pressure.
To a suspension of NaH (546 mg, 60% in mineral oil, 13.7
mmol) in dry CH2Cl2 (80 mL) was slowly added dry MeOH
(0.74 mL, 20 mmol) at 0 °C. The mixture was stirred for 10
min, and a solution of the crude benzylidene derivative
dissolved in CH2Cl2 (10 mL) was added dropwise. The mixture
was allowed to warm to room temperature and stirred for 1
h. A saturated NH4Cl solution was added at 0 °C, and the
mixture was extracted with CH2Cl2. The combined extracts
were washed with brine, dried, filtered, concentrated, and
purified by silica gel column chromatography to yield alcohol
benzylidene (3.3 g, 85% overall yield) as a colorless oil: 1H
chromatography, yielding 34 (1.4 g, 93% yield) as a colorless
1
oil: [R]25 + 37.0 (c 2.0, CHCl3); H NMR (CDCl3) δ 0.07 (s,
D
3H), 0.08 (s, 3H), 0.88 (s, 9H), 1.35-1.75 (m, 3H), 2.02 (m, 1H),
2.99 (dd, J ) 5.5, 1.7 Hz, 2H), 3.37 (m, 1H), 3.56 (m, 1H), 3.87
(m, 2H), 5.08 (dd, J ) 10.1, 1.4 Hz, 1H), 5.27 (dd, J ) 16.9,
1.4 Hz, 1H), 5.79 (m, 1H); 13C NMR (CDCl3) δ -4.7 (q), -4.5
(q), 18.0 (s), 23.2 (t), 24.2 (t), 25.7 (q), 32.3 (t), 66.8 (t), 70.7
(d), 73.7 (d), 80.5 (s), 82.8 (s), 116.3 (t), 132.2 (d); IR (film)
(cm-1) 2931, 2872, 2858, 1463, 1252, 1101. Anal. Calcd for
C
16H28O2Si: C, 68.52; H, 10.06. Found: C, 68.54; H, 10.53.
P r ep a r a tion of (2R a n d 2S)-5-[(2R,3S)-3-(ter t-Bu tyld i-
methylsilyloxy)tetrahydro-2H-pyran-2-yl]-4-pentyne-1,2-diol
(35). To a stirred solution of 4-methylmorpholine N-oxide (0.85
g, 7.3 mmol) in H2O (14 mL) were added OsO4 (10 mg, 0.04
mmol) and the alkene 34 (1.2 g, 4.3 mmol) in THF/acetone
(1:1) (28 mL) at room temperature. The mixture was vigorously
stirred overnight. Then it was diluted with EtOAc and washed
J . Org. Chem, Vol. 68, No. 8, 2003 3223