By controlling the reaction conditions, selective desilylation can
be accomplished in the presence of bulkier silyl groups and other
acid-sensitive protecting groups. Nonetheless, the facile condi-
tions, high yields, and demonstrated applicability to complex,
highly functionalized molecules suggest that this protocol will find
widespread utility in synthesis.
2-[4ꢀ-(tert-Butyldimethylsilyloxy)phenyl]ethanol. See Table 3,
entry 1a, ref. 21.
2-[4ꢀ-(Tri-isopropylsilyloxy)phenyl]ethanol. Table 3, entry 1b.
1H NMR (400 MHz, CDCl3) d 7.07 (2H, d, J = 8.4 Hz), 6.83 (2H,
d, J = 8.4 Hz), 3.82 (2H, t, J = 6.5 Hz), 2.80 (2H, t, J = 6.5 Hz),
1.59 (1H, brs), 1.20–1.29 (18H, m), 1.05–1.10 (3H, m); 13C NMR
(100 MHz, CDCl3) d 154.6, 130.5, 129.8, 119.9, 63.8, 38.3, 17.9,
12.6.
Experimental
2-[4ꢀ-(tert-Butyldiphenylsilyloxy)phenyl]ethanol. Table 3, entry
General
1
1c. Eluted with diethylether–pentane = 3 : 1, colorless oil; H
1H NMR (300 or 400 MHz) and 13C NMR (75 or 100 MHz)
were recorded at room temperature in CDCl3 with Varian-Unity
spectrometers. Chemical shifts (d) are in parts per million relative
NMR (400 MHz, CDCl3) d 7.33–7.71 (10H, m), 6.93 (2H, d, J =
8.4 Hz), 6.70 (2H, d, J = 8.4 Hz), 3.74 (2H, t, J = 6.5 Hz), 2.71 (2H,
t, J = 6.5 Hz), 1.53 (1H, brs), 1.09 (9H, s); 13C NMR (100 MHz,
CDCl3) d 154.1, 135.4, 132.9, 130.6, 129.8, 129.6, 127.7, 119.7,
63.6, 38.2, 26.5, 19.4.
to CHCl3 (7.26, H), CDCl3 (77.0, 13C). Coupling constants are
1
given as absolute values expressed in Hz. High resolution mass
spectra were measured on a Waters/Micromass instrument. Thin
layer chromatography was carried out using Merck Kieselgel 60
F254 silica gel plates. Column chromatography separations were
performed using Merck Kieselgel 60 (Art. 7734). Dried solvents
were purchased from Sigma-Aldrich.
2 - [3ꢀ - Methoxy - 4ꢀ - (tert - butyldimethylsilyloxy)phenyl]ethanol.
Table 3, entry 2a. 1H NMR (400 MHz, CDCl3) d 6.65–6.79 (3H,
m), 3.82 (2H, t, J = 6.4 Hz), 3.79 (3H, s), 2.79 (2H, t, J = 6.4 Hz),
1.59 (1H, brs), 0.98 (9H, s), 0.14 (6H, s); 13C NMR (100 MHz,
CDCl3) d 150.9, 143.6, 131.6, 121.0, 120.8, 112.9, 63.7, 55.4, 38.8,
25.7, 18.4, −4.6.
2-[3ꢀ-Methoxy-4ꢀ-(tri-isopropylsilyloxy)phenyl]ethanol. Table 3,
entry 2b. 1H NMR (400 MHz, CDCl3) d 6.65–6.82 (3H, m), 3.82
(2H, t, J = 6.5 Hz), 3.80 (3H, s), 2.80 (2H, t, J = 6.5 Hz), 1.42 (1H,
brs), 1.21–1.30 (3H, m), 1.09–1.10 (18H, m); 13C NMR (100 MHz,
CDCl3) d 151.0, 144.4, 131.5, 121.2, 120.6, 113.3, 63.9, 55.7, 39.0,
18.1, 18.0, 17.9, 13.1.
General procedure for the preparation of silyl ethers1
To a magnetically stirred solution of the alcohol (1.0 mmol), in
dry CH2Cl2 or DMF (3.0 ml), imidazole (1.5 or 3.0 mmol) and
trialkylsilyl chloride (1.5 or 3.0 mmol) were added sequentially.
After the starting material disappeared on TLC, brine was poured
into the reaction mixture. The organic layer was washed with
brine (10.0 ml) twice, separated, dried over MgSO4, filtered,
and concentrated. The resulting residue was purified by flash
chromatography. When DMF was used, the resulting reaction
mixture was directly purified by the flash chromatography elution
with diethylether–pentane (1 : 20).
2 - [3ꢀ - Methoxy - 4ꢀ - (tert - butyldiphenylsilyloxy)phenyl]ethanol.
Table 3, entry 2c. Eluted with diethylether–pentane = 3 : 1,
colorless oil); 1H NMR (400 MHz, CDCl3) d 7.31–7.71 (10H, m),
6.47–6.65 (3H, m), 3.76 (2H, t, J = 6.4 Hz), 3.55 (3H, s), 2.72 (2H,
t, J = 6.4 Hz), 1.57 (1H, brs), 1.10 (9H, s); 13C NMR (100 MHz,
CDCl3) d 150.4, 143.7, 135.3, 133.8, 131.4, 129.5, 127.4, 120.8,
120.1, 113.6, 63.6, 55.3, 38.7, 26.7, 19.7.
General procedure for the preparation of silyl esters1
To a magnetically stirred solution of the acids (1.0 mmol), in dry
DMF (3.0 ml), imidazole (1.5 mmol) and trialkylsilyl chloride
(1.5 mmol) were added sequentially. After the starting material
disappeared on TLC, the resulting reaction mixture was purified
by flash chromatography elution with diethylether–pentane (1 :
20).
2-[3ꢀ -Bromo-4ꢀ -(tert-butyldimethylsilyloxy)phenyl]ethanol.
Table 3, entry 3. 1H NMR (400 MHz, CDCl3) d 6.79–7.39 (3H, m),
3.82 (2H, t, J = 6.4 Hz), 2.77 (2H, t, J = 6.4 Hz), 1.57 (1H, brs),
1.03 (9H, s), 0.24 (6H, s); 13C NMR (100 MHz, CDCl3) d 151.1,
133.6, 132.6, 128.7, 120.1, 115.2, 63.5, 37.9, 25.7, 18.3, −4.2.
4-(tert-Butyldipheylsilyloxy)benzyl alcohol. Table 3, entry 4.
Eluted with diethylether–pentane = 3 : 1, colorless oil; 1H NMR
(400 MHz, CDCl3) d 7.33–7.71 (10H, m), 7.07 (2H, d, J = 8.4 Hz),
6.74 (2H, d, J = 8.4 Hz), 4.51 (2H, s), 1.63 (1H, brs), 1.09 (9H, s);
13C NMR (100 MHz, CDCl3) d 155.1, 135.4, 133.3, 132.8, 129.8,
128.3, 127.7, 119.6, 65.0, 26.4, 19.4.
General procedure for silyl ether and ester cleavage
To a stirred solution of bis-silyl ether, silyl ether or ester
(1.0 mmol) at 0 ◦C or room temperature in MeOH TMSBr (0.1–
0.2 mmol) was added. After stirring for the indicated time the
reaction was quenched by the addition of a saturated aqueous
sodium bicarbonate solution (1 ml) and diluted with water (10 ml).
The product was extracted with ethyl acetate (3 × 10 ml). The com-
bined organic extracts were washed with brine (20 ml) and
concentrated in vacuo. If necessary, the crude product was purified
on silica gel. Elution with diethylether–pentane (1 : 4) or ethyl
acetate–pentane (1 : 1) afforded the required products.
Acknowledgements
We express our gratitude to the Irish Research Council for Science,
Engineering and Technology (IRCSET) and Higher Education
Authority (HEA) for a post-doctoral fellowship, granted to Syed
T. A. Shah. We also acknowledge the facilities provided by the
Centre for Synthesis and Chemical Biology (CSCB), funded by
the Higher Education Authority’s Programme for Research in
Third-Level Institutions (PRTLI). We are grateful to Dr. Jimmy
(5S,6R)-5,6-Dihydroxy-oct-7-enoic acid methyl ester. Table 2,
entry 7, ref. 17.
This journal is
The Royal Society of Chemistry 2008
Org. Biomol. Chem., 2008, 6, 2168–2172 | 2171
©