A R T I C L E S
Trost and Ball
ambient temperature and stirred for 30 min. The crude reaction mixture
was concentrated under reduced pressure and immediately applied to
a silica gel column (eluent with 20:1 petroleum ether:ether). After
purification, 78 mg (86%) of the desired 1,1-disubstituted silane was
isolated as a clear, colorless oil.
(benzyldimethylsilanyl)-7-(4-methoxy-benzyloxy)-1-phenyl-undec-4-en-
6-ol (53.6 mg, 78%) after purification on a silica gel column (eluent:
6:1, then 4:1 petroleum ether:ether).
1
Rf: 0.16 (4:1 petroleum ether:ether). H NMR (300 MHz, CDCl3):
δ 6.85-7.23 (m, 14H), 6.00 (d, J ) 9.5 Hz, 1H), 4.45-4.62 (m, 2H),
4.11-4.17 (m, 1H), 3.87 (s, 3H), 3.12-3.25 (m, 1H), 2.57 (t, J ) 8.1
Hz, 2H), 2.39 (d, J ) 3.2 Hz, 1H), 2.01-2.27 (m, 4H), 1.26-1.67 (m,
8H), 0.89 (t, J ) 6.8 Hz, 3H), 0.08-0.12 (m, 6H). 13C NMR (125
MHz, CDCl3): δ 159.7, 144.5, 142.6, 141.9, 140.0, 130.6, 129.9, 128.7,
128.61, 128.57, 128.42, 126.0, 124.5, 114.2, 83.2, 73.1, 72.7, 55.6,
38.2, 36.1, 32.3, 31.3, 28.2, 26.9, 23.2, 14.3, -1.1, -1.4. IR (thin
film): 3585 (br), 2931, 2361, 1612, 1514, 1249 (s), 1035, 828, 699
cm-1. Anal. Calcd for C34H46O3Si: C, 76.93; H, 8.73. Found: C, 77.04;
H, 8.83.
General Procedure for Ruthenium-Catalyzed Hydrosilylation of
r,â-Alkynyl Carbonyl Compounds: (Z)-5-(Benzyldimethylsilyl)-4-
hepten-3-one, 78. Neat 4-hepyn-3-one (4.14 g, 37.6 mmol) and
benzyldimethylsilane (7.79 mL, 45.1 mmol) were taken up in acetone
(60 mL) at 0 °C under Ar. Solid [Cp*Ru(MeCN)3]PF6 (95 mg, 0.188
mmol) was added, and the ice bath was removed to allow the solution
to reach room temperature. After 30 min, the acetone was removed
under reduced pressure, and the resulting residue was applied directly
to a silica gel plug (ca. 6 cm, eluent 40:1 petroleum ether:ether) to
provide the desired (Z)-vinylsilane (9.61 g, 98%) as a clear, colorless
oil.
Rf: 0.60 (10:1 petroleum ether:EtOAc). 1H NMR (300 MHz,
CDCl3): δ 5.65 (m, 1H), 5.33 (d, J ) 2.7 Hz, 1H), 4.07 (t, J ) 6.8
Hz, 2H), 2.14 (t, J ) 7.8 Hz, 2H), 2.05 (s, 3H), 1.75 (m, 2H), 0.93 (t,
J ) 7.8 Hz, 9H), 0.61 (q, J ) 7.8 Hz, 6H). 13C NMR (75 MHz,
CDCl3): δ 171.2, 147.7, 125.6, 64.2, 32.1, 27.6, 21.0, 7.3, 2.8. IR (thin
film): 2955, 2876, 1745 (s), 1239 (s), 720 cm-1. HRMS-EI (m/z): [M]+
calcd for C13H26O2Si, 242.1702; found, 213.1302 [M - Et].
10-(4-Acetylphenyl)-10-undecenoic Acid Methyl Ester, 35.
Vinylsilane 29 (69 mg, 0.20 mmol) and 4-iodoacetophenone (34 µL,
0.30 mmol) were taken up in THF under Ar at 0 °C. TBAF (0.40 mL,
0.40 mmol, 1.0 M in THF) was then added dropwise, and after 10
min, solid Pd2dba3 (4.5 mg, 0.0050 mmol) was added and the flask
allowed to warm to room temperature. After being stirred for 2 h, the
mixture was diluted with ether (10 mL) and filtered through a plug of
silica gel (ca. 2 cm), washing with additional ether (20 mL). The filtrate
was concentrated under reduced pressure, and the resulting residue was
applied to a silica gel column (eluent 100:8 petroleum ether:EtOAc)
to give 56 mg (89%) of the desired coupling product as a white
crystalline solid.
1
Rf: 0.46 (4:1 petroleum ether:EtOAc). Mp: 38-39 °C. H NMR
(300 MHz, CDCl3): δ 7.93 (d, J ) 8.5 Hz, 2H), 7.48 (d, J ) 8.5 Hz,
2H), 5.35 (d, J ) 1.0 Hz, 1H), 5.16 (d, J ) 1.0 Hz, 1H), 3.66 (s, 3H),
2.60 (s, 3H), 2.51 (t, J ) 7.3 Hz, 2H), 2.29 (d, J ) 7.5 Hz, 2H), 1.60
(m, 2H), 1.43 (m, 2H), 1.22-1.34 (m, 8H). 13C NMR (75 MHz,
CDCl3): δ 197.7, 174.3, 147.8, 146.2, 135.9, 128.4, 126.2, 114.1, 51.4,
35.1, 34.0, 29.1 (2C), 29.0 (2C), 28.1, 26.6, 24.9. IR (thin film): 2930,
2856, 1739 (s), 1683 (s), 1604, 1268, 847 cm-1. Anal. Calcd for
C20H28O3: C, 75.91; H, 8.92. Found: C, 76.12; H, 9.06.
1H NMR (300 MHz, CDCl3): δ 6.98-7.22 (m, 5H), 6.68 (t, J )
1.4 Hz, 1H), 2.55 (q, J ) 7.2 Hz, 2H), 2.37 (s, 2H), 2.15 (qd, J ) 7.3,
1.5 Hz, 2H), 1.13 (t, J ) 7.3 Hz, 1H), 0.89 (t, J ) 7.3 Hz, 1H), 0.10
(s, 6H). 13C NMR (75 MHz, CDCl3): δ 165.4, 140.6, 136.4, 128.4,
128.1, 127.9, 123.8, 36.5, 31.6, 24.8, 13.6, 8.1, -2.3. IR (thin film):
2969, 1690 (s), 1576, 1493, 1246, 1143, 828, 699 cm-1. Additional
characterization is to be provided elsewhere after additional synthetic
operations.
(2R,3S)-1,2,3-Trihydroxy-5-undecanone 1,2-Isopropylidene Ketal,
38. The alkyne 36 (120 mg, 0.50 mmol) and BDMS-H (104 µL, 0.60
mmol) in acetone (1.0 mL) were treated at 0 °C with complex 7 (7.8
mg, 0.015 mmol). The mixture was allowed to warm to room
temperature over 30 min. It was then re-cooled to 0 °C, diluted with
THF (1.5 mL), and TBAF (0.60 mL, 0.60 mmol, 1.0 M solution in
THF) was added dropwise. After 20 min, MeOH (1.0 mL) was
introduced, followed by solid potassium bicarbonate (150 mg, 1.5
mmol) and aqueous H2O2 (0.80 mL, 30% solution). The mixture was
then stirred for 36 h at room temperature, at which time it was diluted
with water (10 mL) and extracted with EtOAc (3 × 10 mL). The organic
extracts were washed with brine (10 mL), dried over Na2SO4, and
concentrated in vacuo. The residue was purified on a silica gel column
(eluent: 85:15:1 petroleum ether:EtOAc:MeOH) to give 99 mg (77%)
of the desired ketone as a single isomeric compound.
1H NMR (500 MHz, CDCl3): δ 4.08 (m, 1H), 3.92-3.95 (m, 3H),
3.27 (br OH, 1H), 2.82 (dd, J ) 7.5, 1.8 Hz, 1H), 2.57 (m, 1H), 2.45
(t, J ) 7.5 Hz, 2H), 1.57 (m, 2H), 1.39 (s, 3H), 1.34 (s, 3H), 1.26-
1.30 (m, 6H), 0.87 (t, J ) 7.0 Hz, 3H). 13C NMR (125 MHz, CDCl3):
δ 212.4, 109.4, 77.5, 69.1, 66.9, 45.1, 43.7, 31.5, 28.8, 26.7, 25.1, 23.5,
23.5, 22.4, 14.0. IR (thin film): 3472 (br, OH), 2932 (s), 1713, 1372,
1215, 1066 (s), 851 (w) cm-1. [R]26D: -21.3° (c 1.3, CHCl3). Anal.
Calcd for C14H26O4: C, 65.09; H, 10.14; Found: C, 64.84; H, 9.92.
(()-(S,S)-4-(Benzyldimethylsilyl)-7-(4-methoxy-benzyloxy)-1-
phenylundec-4-en-6-ol, 70. To a solution of (()-(S,S)-7-(4-methoxy-
benzyloxy)-1-phenylundec-4-yn-6-ol (50 mg, 0.13 mmol) and benzyl-
dimethylsilane (23.7 mg, 0.16 mmol) in CH2Cl2 (0.26 mL) was added
[Cp*Ru(MeCN)3]PF6 (7) (3.3 mg, 0.0065 mmol) at 0 °C. The solution
was allowed to warm to room temperature and stirred for 20 min, at
which time TLC analysis indicated incomplete consumption of the
alkyne. Another portion of complex 7 (3.3 mg, 0.0065 mmol) was
added. The solution was stirred for 20 min, filtered through a plug of
florisil, and concentrated under reduced pressure to yield (()-(S,S)-4-
(2Z,2′E,4′E)-3-(Hexa-2,4-dienyloxydimethysilyl)-2-pentenoic Acid
Ethyl Ester, 103. Ethyl 2-pentynoate (200 µL, 1.52 mmol) under Ar
at 0 °C was taken up in CH2Cl2 (3 mL). Dimethylchlorosilane (202
µL, 1.82 mmol, freshly distilled from CaH2) was added, followed by
solid complex 7 (7.0 mg, 0.015 mmol). The flask was allowed to warm
to room temperature and was stirred for 30 min. The flask was then
re-cooled to 0 °C and was treated sequentially with triethylamine (423
µL, 3.03 mmol) and (E,E)-hexadien-1-ol (sorbol) (290 µL, 2.58 mmol).
Additional CH2Cl2 (3 mL) was added to ensure solubility, and the flask
was warmed to room temperature and stirred for 30 min. The mixture
was diluted with benzene (15 mL) and filtered through Celite, washing
with additional benzene (15 mL). The filtrate was concentrated under
reduced pressure and purified by silica gel chromatography (eluent:
20:1 petroleum ether:ether) to afford 371 mg (87%) of the desired silyl
ether as a clear, colorless oil.
1
Rf: 0.26 (4:1 petroleum ether:ether). H NMR (300 MHz, CDCl3):
δ 7.25 (dd, J ) 8.0, 8.0 Hz, 1H), 6.99 (d, J ) 7.2 Hz, 1H), 6.93 (s,
1H), 6.82 (dd, J ) 8.0, 2.4 Hz, 1H), 5.30 (s, 1H), 5.08 (s, 1H), 4.08 (t,
J ) 7.0 Hz, 2H), 3.82 (s, 3H), 2.56 (t, J ) 7.0 Hz, 2H), 2.05 (s, 3H),
1.79 (tt, J ) 7.0, 7.0 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 171.1,
159.5, 147.1, 142.3, 129.2, 118.6, 113.0, 112.5, 112.1, 63.9, 55.2, 31.7,
27.1, 21.0. IR (thin film): 2956, 1739 (s), 1577, 1240 (s), 1041 cm-1
.
Further characterization will be reported after formation of 114.
(1R,2S,5R,6R)-6-Ethyl-5-hydroxymethyl-2-methylcyclohex-3-
enecarboxylic Acid Ethyl Ester, 105. The starting triene (102 mg,
0.361 mmol) was taken up in benzene-d6 (4 mL) in a Teflon-ringed
screw-top vial and placed in a 180 °C bath for 20 h. The solution was
then transferred to a round-bottomed flask and the solvent removed
under reduced pressure. The residue was taken up in DMF (1.5 mL)
and treated with TBAF (1.5 mL, 1.50 mmol, 1.0 M in THF). The
solution was brought to 75 °C and stirred for 4 h. The mixture was
cooled to room temperature, saturated aqueous NaHCO3 (15 mL) and
water (15 mL) were added, and the mixture was extracted with EtOAc
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17654 J. AM. CHEM. SOC. VOL. 127, NO. 50, 2005