The Journal of Organic Chemistry
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2,5-Dimethoxyphenol (3h).37 Using general procedure A, silane 5h
(109 mg, 0.48 mmol) afforded 58 mg (78%); using general procedure
B, silane 5h (105 mg, 0.46 mmol) afforded 65 mg (91%); using
general procedure C, silane 2h (98 mg, 0.50 mmol) afforded 60 mg
(79%). Purification by column chromatography (petroleum ether →
petroleum ether/Et2O (4:1)) produced a colorless oil; Rf 0.36
4-(Methoxydimethylsilyl)benzonitrile (5a). Using general proce-
dure E, silane 2a (50 mg, 0.310 mmol) afforded a colorless oil (56 mg,
95%); Rf 0.34 (petroleum ether/Et2O (9:1)); IR (thin film, νmax
/
1
cm−1) 2960w, 2229m, 1386w, 1255m, 1083s, 823s; H NMR (400
MHz, CDCl3) δH 0.40 (6H, s), 3.46 (3H, s), 7.66 (4H, d, J 1.5); 13C
NMR (100 MHz, CDCl3) δC −2.43, 50.8, 113.2, 118.9, 131.2, 133.9,
144.2; HRMS (ES+) calc. for C10H13NNaOSi [M + Na]+ 214.0659,
found 214.0656.
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(petroleum ether/Et2O (9:1)); H NMR (400 MHz, CDCl3) δH 3.76
(3H, s), 3.86 (3H, s), 5.73 (1H, br s), 6.39 (1H, dd, J 9.0, 3.0), 6.57
(1H, d, J 3.0), 6.79 (1H, d, J 9.0); 13C NMR (100 MHz, CDCl3) δC
55.6, 56.6, 101.7, 104.2, 111.5, 140.9, 146.4, 154.6.
1-(4-(Methoxydimethylsilyl)phenyl)ethanone (5b). Using general
procedure E, silane 2b (286 mg, 1.60 mmol) afforded a colorless oil
(320 mg, 96%); Rf 0.49 (petroleum ether); IR (thin film, νmax/cm−1)
1684s, 1388 m, 1243s, 1081s, 820s, 785s; 1H NMR (400 MHz,
CDCl3) δH 0.41 (6H, s), 2.62 (3H, s), 3.46 (3H, s), 7.68 (2H, d, J 8.0),
7.95 (2H, d, J 8.0); 13C NMR (100 MHz, CDCl3) δC −2.36, 26.7, 50.8,
127.4, 133.7, 137.8, 143.9, 198.5; HRMS (ES+) calc. for C11H16NaO2Si
[M + Na]+ 231.0812, found 231.0812.
Pyridin-3-ol (3i).4f Using general procedure A, silane 2i (150 mg,
1.09 mmol) afforded 81 mg (78%); using general procedure B, silane
2i (69 mg, 0.50 mmol) afforded 33 mg (71%). Purification by column
chromatography (CHCl3 → CHCl3/MeOH (9:1)) produced a white
solid; Rf 0.25 (CHCl3/MeOH (9:1)); mp 123−125 °C (Lit. 127−129
°C); 1H NMR (500 MHz, DMSO−d6) 7.14−7.16 (1H, m), 7.20 (1H,
dd, J 8.0, 4.5), 8.03 (1H, dd, J 4.5, 1.5), 8.13 (1H, d, J 2.5), 9.86 (1H,
br s); 13C NMR (125 MHz, DMSO−d6)) δC 122.0, 124.1, 138.0,
140.2, 153.6.
Methoxydimethyl(4-(trifluoromethyl)phenyl)silane (5c). Using
general procedure E, silane 2c (250 mg, 1.22 mmol) afforded a
colorless oil (254 mg, 89%); Rf 0.51 (petroleum ether/Et2O (9:1)); IR
4-(((tert-Butyldimethylsilyl)oxy)methyl)phenol (3j).12a Using gen-
eral procedure C (although oxidation quenched with NH4Cl (1 mL,
sat., aq.) instead of 1N HCl), silane 2j (140 mg, 0.50 mmol) afforded
88 mg (74%). Purification by column chromatography (petroleum
ether +1% Et3N → petroleum ether/Et2O (1:1) + 1% Et3N) produced
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(thin film, νmax/cm−1) 1324s, 1256w, 1164m, 1124s, 1059s, 822s; H
NMR (400 MHz, CDCl3) δH 0.46 (6H, s), 3.51 (3H, s), 7.69 (2H, d, J
8.0), 7.75 (2H, d, J 8.0); 13C NMR (100 MHz, CDCl3) δC −1.92, 51.2,
124.6 (q, J 272.5), 124.9 (q, J 3.5), 132.0 (q, J 32.0), 134.2, 142.8;
HRMS (FI+) calc. for C10H13F3OSi [M]+ 234.0688, found 234.0687.
(4-Bromophenyl)(methoxy)dimethylsilane (5d). Using general
procedure E, silane 2d (160 mg, 0.653 mmol) afforded a colorless
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a colorless oil; Rf 0.45 (petroleum ether/Et2O (9:1)); H NMR (400
MHz, CDCl3) δH 0.94 (6H, s), 0.94 (9H, s), 4.66 (2H, s), 5.26 (1H, br
s), 6.81 (2H, d, J 7.5), 7.18 (2H, d, J 7.5); 13C NMR (100 MHz,
CDCl3) δC −5.17, 18.44, 26.0, 64.8, 115.2, 127.8, 133.1, 155.1.
2,6-Dimethylphenol (3k).4f Using general procedure C, silane 2k
(82 mg, 0.50 mmol) afforded 54 mg (88%). Purification by column
chromatography (petroleum ether → petroleum ether/Et2O (95:5))
oil (155 mg, 85%); Rf 0.49 (petroleum ether); IR (thin film, νmax
/
cm−1) 2958w, 1575w, 1479w, 1376w, 1255m, 1066s, 1009m; 1H NMR
(500 MHz, CDCl3) δH 0.42 (6H, s), 3.49 (3H, s), 7.49 (2H, t, J 8.0),
7.58 (2H, d, J 8.0); 13C NMR (100 MHz, CDCl3) δC −1.19, 51.1,
125.0, 131.5, 135.5, 136.7; HRMS (FI+) calc. for C9H13BrOSi [M]+
245.9899, found 245.9918.
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produced a waxy solid; Rf 0.21 (petroleum ether/Et2O (9:1)); H
(4-Fluorophenyl)(methoxy)dimethylsilane (5e).31 Using general
procedure E, silane 2e (400 mg, 2.66 mmol) afforded a colorless oil
(423 mg, 86%); Rf 0.56 (petroleum ether; IR (thin film, νmax/cm−1)
NMR (500 MHz, CDCl3) δH 2.32 (6H, s), 4.67 (1H, br s), 6.83 (1H,
t, J 7.5), 7.05 (2H, d, J 7.5); 13C NMR (125 MHz, CDCl3) δC 16.3,
120.7, 123.4, 129.0, 152.6.
1,2,4-Trimethoxy-5-(1-methoxyethyl)benzene (3l).26 Using gen-
eral procedure C (although oxidation quenched with Na2S2O3 (1 mL,
sat., aq.) instead of 1N HCl), silane 2l (120 mg, 0.50 mmol) was
converted to a crude phenolic product which was immediately
dissolved in anhydrous THF (5 mL) and cooled to 0 °C. NaH (80 mg,
2.00 mmol, 4 equiv) was added and the reaction was stirred at 0 °C for
1 h before the addition of iodomethane (186 μL, 3.00 mmol, 6.0
equiv). After stirring overnight, the reaction was quenched with
MeOH (1 mL) and concentrated in vacuo. The concentrate was
dissolved in EtOAc (5 mL) and washed with water (3 × 5 mL). The
organic phase was dried (MgSO4) and concentrated in vacuo to afford
a yellow oil which was purified by column chromatography (petroleum
ether → petroleum ether/Et2O (9:1)) to afford a colorless oil (45 mg,
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1589m, 1450w, 1252w, 1231w, 1082s; H NMR (500 MHz, CDCl3)
δH 0.38 (6H, s), 3.44 (3H, s), 7.09 (2H, t, J 9.0), 7.56 (2H, dd, J 9.0,
6.5); 13C NMR (100 MHz, CDCl3) δC −2.27, 50.6, 115.0 (d, J 19.5),
133.0 (d, J 4.0), 135.5 (d, J 7.5), 164.0 (d, J 248.5); HRMS (FI+) calc.
for C9H13FOSi [M]+ 184.0720, found 184.0719.
Methoxydimethyl(p-tolyl)silane (5f).39 Using general procedure E,
silane 2f (150 mg, 1.00 mmol) afforded a colorless oil (160 mg, 89%);
Rf 0.53 (petroleum ether); IR (thin film, νmax/cm−1) 1604w, 1250m,
1083s, 828s, 777s; 1H NMR (400 MHz, CDCl3) δH 0.39 (6H, s), 2.39
(3H, s), 3.46 (3H, s), 7.24 (2H, d, J 7.5), 7.50 (2H, d, J 7.5); 13C NMR
(100 MHz, CDCl3) δC −2.29, 21.5, 50.6, 128.7, 133.5, 133.8, 139.6;
HRMS (FI+) calc. for C10H16OSi [M]+ 180.0970, found 180.0969.
Methoxy(4-methoxyphenyl)dimethylsilane (5g).40 Using general
procedure E, silane 2g (100 mg, 0.66 mmol) afforded a colorless oil
(122 mg, 99%); Rf 0.33 (petroleum ether); 1H NMR (400 MHz,
CDCl3) δH 0.38 (6H, s), 3.44 (3H, s), 3.84 (3H, s), 6.95 (2H, d, J 8.5),
7.53 (2H, d, J 8.5); 13C NMR (100 MHz, CDCl3) δC −1.84, 51.0, 55.5,
114, 128.8, 135, 161.3.
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40%); Rf 0.19 (petroleum ether/Et2O (9:1)); H NMR (400 MHz,
CDCl3) δH 1.38 (3H, d, J 6.5), 3.25 (3H, s), 3.81 (3H, s), 3.86 (3H, s),
3.90 (3H, s), 4.72 (1H, q, J 6.5), 6.52 (1H, s), 6.93 (1H, s); 13C NMR
(100 MHz, CDCl3) δC 22.7, 56.1, 56.4, 56.5, 56.5, 72.7, 97.5, 109.5,
123.3, 143.5, 148.4, 150.8.
(4-Methoxyphenyl)dimethylsilanol (4).38 To a solution of silane 2g
(250 mg, 1.50 mmol, 1.0 equiv) and water (500 μL, 30 mmol, 20
equiv) in MeCN (5 mL), under air, was added [RuCl2(p-cymene)]2
(18 mg, 0.03 mmol, 2 mol %). After 2/3 s of effervescence, the
reaction was seen to be complete by TLC. The reaction was diluted
with petrol (2 mL) and eluted through a silica plug (petroleum ether/
Et2O (9:1)) to afford the title compound as a colorless liquid (270 mg,
(2,5-Dimethoxyphenyl)(methoxy)dimethylsilane (5h). Using gen-
eral procedure E, silane 2h (209 mg, 1.06 mmol) afforded a colorless
oil (214 mg, 89%); Rf 0.55 (petroleum ether/Et2O (9:1)); IR (thin
1
film, νmax/cm−1) 2955m, 2832m, 1158w, 1481s, 1272s, 1147m; H
NMR (400 MHz, CDCl3) δH 0.38 (6H, s), 3.53 (3H, s), 3.78 (3H, s),
3.80 (3H, s), 6.80 (1H, d, J 9.0), 6.90 (1H, dd, J 9.0, 3.0), 7.05 (1H, d,
J 3.0); 13C NMR (100 MHz, CDCl3) δC −1.66, 50.9, 55.7, 55.8, 110.7,
115.7, 120.9, 126.8, 153.5, 158.3; HRMS (ES+) calc. for C11H18NaO3Si
[M + Na]+ 249.0917, found 249.0920.
Preparation of Celite/Pd/C Column. A glass chromatography
column (12.5 mm internal diameter) was packed with 1.5 g Celite (40
mm height). Pd/C (10 mg, 10 wt % loading, 0.010 mmol) was mixed
with Celite (1.0 g), loaded onto the column above the Celite and
packed down (25 mm height). The column was wetted with MeOH (5
mL) under a positive pressure of N2.
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92%); Rf 0.21 (petroleum ether/Et2O (85:15)); H NMR (400 MHz,
CDCl3) δH 0.39 (6H, s), 2.10 (1H, s), 3.83 (3H, s), 6.94 (2H, m), 7.53
(2H, m); 13C NMR (100 MHz, CDCl3) δC 0.08, 55.1, 113.6, 130.2,
134.6, 160.8.
Synthesis of Methoxysilanes via Ruthenium catalysis,
General Procedure E. [RuCl2(p-cymene)]2 (0.5 mol %) was
added to the hydrosilane in MeOH (5 M), under air. After 2/3 s of
effervescence the reaction was seen to be complete by TLC. The
reaction mixture was diluted in Et2O and eluted through a silica plug
(Et2O) to afford methoxy silane.
Large Scale Preparation of 2,5-Dimethoxyphenol (3h). A solution
of silane 2h (1.96 g, 10.0 mmol, 1.0 equiv) in MeOH/THF (1:1, 20
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dx.doi.org/10.1021/jo301363h | J. Org. Chem. 2012, 77, 7052−7060