6904 J . Org. Chem., Vol. 61, No. 20, 1996
Pilcher and DeShong
(s), 3067 (m), 3035 (m), 2233 (w), 2204 (w), 1031 (vs); 1H NMR
(CDCl3) 7.40 (10H, m), 5.69 (1H, d, 6), 2.41 (1H, d, 6); 13C NMR
(CDCl3) 140.6, 133.1, 131.7, 128.7, 128.6, 128.4, 128.3, 126.7,
88.7, 86.7, 65.1.
r-(2-(1,3-D i t h i a n y l))-r-(t r i m e t h y ls i lo x y )m e t h y l-
ben zen e (6). This reaction was done on a 2.00 mmol scale,
and the crude product was purified by flash column chroma-
tography (hexanes/Et2O gradient) to give 576 mg of the
trimethylsilyl ether as a clear, colorless oil (>99% pure by GC,
96% yield): IR (CCl4) 3090 (w), 2958 (s), 2900 (s), 1425 (m),
1252 (vs), 1088 (vs), 1072 (vs), 890 (vs), 845 (vs); 1H NMR
(CDCl3) 7.34 (5H, m), 4.76 (1H, d, 7), 4.28 (1H, d, 7), 2.80 (4H,
m), 2.03 (1H, m), 1.86 (1H, m); 13C NMR (CDCl3) 141.3, 128.0,
127.9, 126.6, 77.6, 54.7, 30.0, 29.8, 25.7, 0.2.
â-P h en yl-r-(tr im eth ylsiloxy)eth ylben zen e (8) [18044-
11-6]. This reaction was done on a 5.00 mmol scale, and the
crude product was purified by flash column chromatography
(hexanes) to give 1.33 g of the trimethylsilyl ether as a clear,
colorless oil (95% pure by GC, 93% yield): IR (CCl4) 3030 (s),
2957 (s), 1604 (m), 1251 (vs), 1094 (vs), 1069 (vs), 943 (s), 842
(vs); 1H NMR (CDCl3) 7.31-7.14 (10H, m), 4.77 (1H, t, 6), 2.91
(2H, d, 6), -0.16 (9H, s); 13C NMR (CDCl3) 144.9, 139.1, 136.0,
129.8, 128.0, 127.0, 126.1, 125.8, 76.4, 47.5, -0.3.
4-Hyd r oxy-1-n on en e (14) [35192-73-5]. This reaction was
done on a 1.00 mmol scale, and the crude product was purified
by flash column chromatography (hexanes/Et2O gradient) to
give 33 mg of the homoallylic alcohol as a clear, colorless oil
(>99% pure by GC, 23% yield): IR (CCl4) 3629 (b, m) 3592 (b,
m), 3080 (m), 2957 (vs), 2862 (vs), 1642 (s), 1069 (s), 1024 (s),
995 (vs), 918 (vs); 1H NMR (CDCl3) 5.84 (1H, m), 5.15 (2H,
m), 3.65 (1H, m), 2.32 (1H, m), 2.13 (1H, m), 1.59 (1H, d, 4),
1.34 (8H, m), 0.89 (3H, t, 6); 13C NMR (CDCl3) 134.9, 118.0,
70.7, 41.9, 36.7, 31.8, 25.3, 22.6, 14.0.
4-Hyd r oxy-5-p h en yl-1-h exen e (16) [77383-06-3]. This
reaction was done on a 5.00 mmol scale, and the crude product
was purified by flash column chromatography (hexanes/Et2O
gradient) to give 935 mg of the benzyl alcohol as a clear,
colorless oil in 73% yield (97% pure by GC, 85:15 erythro:threo
as determined by GC and 1H NMR). Data given for erythro:
IR (CCl4) 3685 (b, w), 3589 (b, m), 3082 (m), 2978 (s), 1690
(vs), 1640 (m), 1265 (vs), 1012 (vs), 997 (vs), 992 (s); 1H NMR
(CDCl3) 7.34-7.20 (5H, m), 5.80 (1H, m), 5.11 (2H, m), 3.71
(1H, dt, 5 and 4), 2.77 (1H, dt, 7 and 7), 2.18 (1H, m), 2.03
(1H, m), 1.72 (1H, bs), 1.34 (3H, d, 7); 13C NMR (CDCl3) 144.4,
135.0, 128.4, 127.7, 126.4, 118.0, 75.0, 45.3, 39.5, 16.3.
1-Allyl-1-(tr im eth ylsiloxy)cycloh exa n e (20). This reac-
tion was done on a 2.00 mmol scale, and the crude product
was purified by flash column chromatography (hexanes/Et2O
gradient) to give 120 mg of the homoallylic trimethylsilyl ether
as a clear, colorless oil (98% pure by GC, 28% yield): IR (CCl4)
3076 (m), 2939 (vs), 1639 (m), 1249 (vs), 1065 (vs), 897 (m),
843 (m); 1H NMR (CDCl3) 5.86 (1H, m), 5.03 (2H, m), 2.26 (2H,
d, 6), 1.62-1.26 (10H, m), 0.12 (9H, s); 13C NMR (CDCl3) 135.0,
116.8, 46.3, 38.0, 25.8, 22.5, 2.7.
with aldehydes, ketones, imines, and alkyl halides in good
yields. Further applications of this technology to syn-
thesis of biologically active substances will be reported
in due course.
Exp er im en ta l Section
Gen er a l Exp er im en ta l. Flash column chromatography
was performed using thick-walled glass columns and “medium-
pressure” silica (230-400 mesh, Merck). All solvents were
distilled from calcium chloride prior to use unless noted
otherwise. Tetrahydrofuran (THF) was distilled from sodium/
benzophenone ketyl. All reagents were distilled, recrystallized,
or chromatographed prior to use unless otherwise noted.
Gas chromatography was performed using a gas chromato-
graph equipped with a flame ionization detector and a 25-m
capillary column coated with cross-linked methyl silicone. All
compounds for which elemental analysis was not obtained
were >95% pure as judged by gas chromatographic and NMR
spectral analysis. 1H and/or 13C NMR spectra of these
substances are included in the supporting information.
Ca r ba n ion Ad d ition to Ald eh yd es a n d Keton es. For
nonenolizable substrates, 0.1 equiv of TBAT and 2 equiv of
the TMS reagent were used. For enolizable substrates, 1 equiv
of TBAT and 10 equiv of the reagent were used to promote
the carbanion addition pathway over the aldol condensation
pathway. Reactions were followed by GC, and the following
two examples are illustrative.
Syn t h esis of 4-P h en yl-4-h yd r oxy-1-bu t en e (10) [936-
58-3]. (All Registry numbers supplied by authors.) Benzal-
dehyde (102 µL, 1.00 mmol), allyltrimethylsilane (318 µL, 2.00
mmol), and tetrabutylammonium triphenyldifluorosilicate
(TBAT, 54 mg, 0.10 mmol) were dissolved in THF (5 mL). The
clear, colorless solution was heated in a 70 °C oil bath under
N2. After 5 min, the solution had changed to yellow, and after
10 min, the reaction was complete. The THF and excess
allyltrimethylsilane were removed at reduced pressure. The
concentrate was redissolved in 30 mL of Et2O and washed with
1 M HCl (30 mL, stirred until the TMS group was completely
hydrolyzed as determined by GC), water (30 mL), and 5%
NaHCO3 (30 mL), then dried (MgSO4), and concentrated at
reduced pressure. The crude alcohol was flash column chro-
matographed (hexanes/Et2O) to give 139 mg (93%) of homo-
allylic alcohol 10 as a clear, colorless oil (99% pure by GC):
1
IR (CCl4) 3619 (s), 3067 (m), 2913 (m), 1639 (m), 1042 (s); H
NMR (CDCl3) 7.34 (5H, m), 5.82 (1H, m), 5.16 (2H, m), 4.72
(1H, t, 7), 2.50 (2H, m), 2.15 (1H, bs); 13C NMR (CDCl3) 143.8,
134.4, 128.3, 127.4, 125.8, 118.2, 73.3, 43.7.
Syn th esis of 4-P h en yl-4-h yd r oxy-1-p en ten e (18) [4743-
74-2]. Acetophenone (238 mL, 2.00 mmol), allyltrimethyl-
silane (3.18 mL, 20 mmol), and TBAT (1.08 g, 2.00 mmol) were
dissolved in THF (10 mL). The clear, colorless solution was
heated in a 70 °C oil bath under N2. After 4 min, the solution
turned orange, and after 40 min, the reaction was complete.
The THF and excess allyltrimethylsilane were removed at
reduced pressure. The concentrate was redissolved in 50 mL
of 50/50 Et2O/EtOAc, then chilled to 5 °C, and filtered to
remove any excess TBAT. The filtrate was washed with 1 M
HCl (50 mL, stirred until the TMS group was completely
hydrolyzed as determined by GC), water (2 × 50 mL), and 5%
NaHCO3 (50 mL), then dried (MgSO4), and concentrated at
reduced pressure. The crude alcohol was flash column chro-
matographed (hexanes/Et2O gradient) to give 293 mg (88%)
of homoallylic alcohol 18 as a clear, colorless oil (98% pure by
GC): IR (CCl4) 3606 (m), 3568 (m), 3082 (m), 2982 (vs), 1641
(m), 1602 (m), 1448 (vs), 1071 (vs), 1001 (vs), 928 (vs), 916
(vs), 866 (m); 1H NMR (CDCl3) 7.43 (2H, m), 7.34 (2H, m), 7.23
(1H, m), 5.62 (1H, m), 5.12 (2H, m), 2.68 (1H, dd, 14 and 6),
2.50 (1H, dd, 14 and 8), 2.08 (1H, s), 1.55 (3H, s); 13C NMR
(CDCl3) 147.6, 133.6, 128.1, 126.6, 124.7, 119.3, 73.6, 48.4, 29.8.
r-Hyd r oxy-1-ben zyl-2-p h en yla cetylen e (4) [1817-49-8].
This reaction was done on a 2.00 mmol scale and the crude
product was purified by flash column chromatography (hex-
anes/CH2Cl2 gradient) to give 338 mg of the propargyl alcohol
as a yellow oil (98% pure by GC, 81% yield): IR (CCl4) 3603
1-Allyl-1-(tr im eth ylsiloxy)cyclop en ta n e (22). This reac-
tion was done on a 2.00 mmol scale, and the crude product
was purified by flash column chromatography (hexanes/Et2O
gradient) to give 38 mg of the homoallylic trimethylsilyl ether
as a clear, colorless oil (89% pure by GC, 9% yield): IR (CCl4)
3077 (m), 2961 (vs), 1639 (m), 1262 (vs), 1250 (vs), 1070 (vs),
1
1056 (vs), 861 (vs), 843 (vs); H NMR (CDCl3) 5.89 (1H, m),
5.04 (2H, m), 2.31 (2H, dt, 7 and 2), 1.78-1.50 (8H, m), 0.11
(9H, s).
Syn th esis of 4-(N-P h en ylam in o)-4-ph en yl-1-bu ten e (24).
Benzylideneaniline (905 mg, 5 mmol), allyltrimethylsilane
(7.95 mL, 50 mmol), and TBAT (5.40 g, 10 mmol) were
dissolved in THF (25 mL). The reaction mixture was heated
at 70 °C and monitored by GC. After 30 h, the reaction had
stopped at 89% completion. The THF and excess allyltri-
methylsilane were evaporated at reduced pressure. The
concentrate was then redissolved in 100 mL of 50/50 Et2O/
EtOAc, chilled to 5 °C for 2 h, and filtered to remove any excess
TBAT. The filtrate was washed with water (2 × 50 mL) and
brine (50 mL) and then concentrated to a red oil at reduced
pressure. The red oil was purified by flash column chroma-
tography (hexanes/CH2Cl2 gradient) to give 824 mg (95% pure