2244 J . Org. Chem., Vol. 65, No. 7, 2000
Notes
Sch em e 1. F or m a tion of Mon op r otected Bisa cetylen es by th e Br om o-Iod o Str a tegy
[(3-Cya n op r op yl)d im eth ylsilyl]a cetylen e (1). Ethynyl-
magnesium bromide (800 mL, 0.5 M in THF; 0.40 mol, precooled
to 5-8 °C) was added to a solution of (3-cyanopropyl)dimethyl-
silyl chloride (64.7 g, 0.40 mol) in THF (200 mL) at -20 °C over
1 h. The cooling bath was removed, and the dark mixture was
allowed to stir overnight. After reduction of the solution volume
to about 200 mL, ether (500 mL) and water (100 mL) were slowly
added. The organic layer was separated and extracted with
water and brine and dried over MgSO4. Evaporation of the
solvent gave a black oil which was purified by vacuum distilla-
tion to give 1 (49.3 g, 81%) as a colorless oil (bp: 62 °C, 1 mbar).
1H NMR (CDCl3) 2.41 (s, 1 H), 2.40 (t, J ) 7.1 Hz, 2 H), 1.82-
1.70 (m, 2 H), 0.81-0.75 (m, 2 H), 0.19 (s, 6 H); 13C NMR (CDCl3)
Sch em e 2
acetylene. Coupling of 3 with TIPS-acetylene, purification
of 5 and subsequent treatment with potassium carbonate
in MeOH/THF (1:1) overnight gives the mono-TIPS-
protected bisacetylene 6 in nearly quantitative yield. This
result clearly shows that 1 can be used in the desired
way, although 6 is also readily available by the use of
the bromo-iodo strategy mentioned above.11 However, the
protocol described here works also in cases where the
bromo position of the bromo-iodo compounds is not
reactive enough for a subsequent second acetylene cou-
pling. Treatment of 7 with 1.1 equiv of 1, and then with
a small excess of TIPS acetylene in a one-pot reaction
gives the CPDMS-TIPS-protected bisacetylene 8 in 33%
isolated yield (Scheme 4). Again, all side products have
significantly different Rf values enabling the easy separa-
tion of 8. Potassium carbonate-induced deprotection of
the CPDMS group gives the mono-TIPS-protected bisacet-
ylene 9 in nearly quantitative yield. As already men-
tioned, 9 is not available by the bromo-iodo protocol
because the intermediate aryl bromide does not undergo
a clean Hagihara coupling under the typical conditions.12
In summary, we have shown that CPDMS-acetylene
can be easily prepared from commercially available
starting materials, can be coupled with aryl iodides under
palladium/copper catalysis, and can be easily deprotected
under the mild conditions used for the deprotection of
the well-established TMS acetylene. In addition, its high
polarity allows for the simple and high yield chromato-
graphic separation of its palladium-catalyzed coupling
products with aryl iodides. Applications of this new
protective group in the synthesis of shape-persistent
macrocycles are in progress and will be published else-
where.
119.7, 94.7, 88.3, 20.6, 20.5, 15.5, -2.0. Anal. Calcd for C8H13
-
NSi: C, 63.51; H, 8.66; N, 9.26. Found: C, 63.49; H, 8.77; N,
9.19.
1-[2-[(3-Cya n op r op yl)d im eth ylsilyl]eth yn yl]-4-iod oben -
zen e (3). To a solution of 1,4-diiodobenzene (2) (2.00 g, 6.06
mmol) and 1 (0.91 g, 6.06 mmol) in piperidine (20 mL) were
added Pd(PPh3)2Cl2 (40 mg), PPh3 (40 mg), and CuI (20 mg) at
room temperature. After stirring for 3 h, dichloromethane and
water were added. The organic phase was separated, extracted
with water, 10% acetic acid, water, 10% aqueous NaOH, and
brine, and dried over MgSO4. Evaporation of the solvent yielded
a brownish residue, which was chromatographed over silica gel
using petroleum ether/dichloromethane (1:1; Rf ) 0.52) as the
eluent to afford 3 (830 mg, 39%) as a yellow oil which solidifies
at room temperature. 1H NMR (CDCl3) 7.66-7.60 (m, 2 H),
7.18-7.12 (m, 2 H), 2.44 (t, J ) 6.9 Hz, 2 H), 1.87-1.77 (m, 2
H), 0.88-0.82 (m, 2 H), 0.26 (s, 6 H); 13C NMR (CDCl3) 133.6,
122.5, 119.8, 105.6, 95.0, 94.0, 20.8, 20.7, 15.9, -1.7. Anal. Calcd
for C14H16INSi: C, 47.60; H, 4.57; N, 3.96. Found: C, 47.69; H,
4.58; N, 3.87.
1-[2-[(3-Cya n op r op yl)d im eth ylsilyl]eth yn yl]-4-[2-(tr iiso-
p r op ylsilyl)eth yn yl]ben zen e (5). Pd(PPh3)2Cl2 (15 mg), PPh3
(15 mg), and CuI (10 mg) were added to a solution of 3 (291 mg,
0.82 mmol) and (triisopropylsilyl)acetylene (300 mg, 1.65 mmol)
in piperidine (25 mL) at room temperature, and the mixture was
then stirred for 3 h at 40 °C. After the reaction was cooled to
room temperature, ether and water were added. The organic
phase was separated and extracted with water, 10% acetic acid,
water, 10% aqueous NaOH, and brine, and dried over MgSO4.
Evaporation of the solvent yielded an yellowish residue, which
was chromatographed over silica gel using petroleum ether/
dichloromethane (1:1; Rf ) 0.70) as the eluent to afford 5 (315
1
mg, 94%) as a colorless oil. H NMR (CDCl3) δ 7.50-7.30 (m, 4
H), 2.44 (t, J ) 6.9 Hz, 2 H), 1.88-1.78 (m, 2 H), 1.13 (s, 21 H),
0.95-0.80 (m, 2 H), 0.26 (s, 6 H). 13C NMR (CDCl3) 131.9, 131.8,
123.9, 122.5, 119.6, 106.5, 106.0, 94.0, 93.1, 20.7, 20.5, 18.7, 15.7,
11.3, -1.9. Anal. Calcd for C25H37NSi2: C, 73.64; H, 9.15; N,
3.44. Found: C, 73.36; H, 9.18; N 3.95.
Exp er im en ta l Section
Gen er a l. Commercially available chemicals were used as
received. 2,6-Diiodo-4-methylanisole was prepared according to
the literature procedure.13 THF was distilled from potassium
prior to use. Piperidine was distilled from CaH2 and stored under
argon. 1H and 13C NMR spectra were recorded in CDCl3 or CD2-
Cl2 at 300 K (300 MHz for proton and 75.5 MHz for carbon),
and chemical shifts are given relative to solvent signals or to
TMS. Thin-layer chromatography was performed on aluminum
plates precoated with Merck 5735 silica gel 60 F254. Column
chromatography was performed with Merck silica gel 60 (230-
400 mesh). Microanalysis were performed by the University of
Mainz. WARNING: (3-Cyanopropyl)dimethylsilyl chloride is a
hazardous (toxic) compound. The synthesis of 1 as well as all
subsequent applications should be carried out with care.
1-Eth yn yl-4-[2-(tr iisop r op ylsilyl)eth yn yl]ben zen e (6). K2-
CO3 (280 mg, 2.03 mmol) was added to a solution of 5 (300 mg,
0.74 mmol) in THF/MeOH (1:1; 10 mL), and the mixture was
stirred overnight at room temperature. The mixture was poured
into ether and water, and the organic layer was extracted with
water and brine and dried over MgSO4. Evaporation of the
solvent yielded an yellowish residue, which was chromato-
graphed over silica gel using petrolether/dichloromethane (2:1;
Rf ) 0.72) as the eluent to afford 6 (185 mg, 89%) as a slightly
yellow oil which slowly solidified. 1H NMR (CD2Cl2) 7.43 (s, 4
H), 3.23 (s, 1 H), 1.14 (s, 21 H). 13C NMR (CD2Cl2) 132.3, 132.2,
124.4, 122.4, 106.7, 93.5, 83.4, 79.2, 18.8, 11.7. Anal. Calcd for
C19H26Si: C, 80.78; H, 9.28. Found: C, 80.47; H, 9.35.
1-[2-[(3-Cya n op r op yl)d im eth ylsilyl]eth yn yl]-4-m eth yl-6-
[2-(tr iisop r op ylsilyl)eth yn yl]a n isole (8). Pd(PPh3)2Cl2 (40
mg), PPh3 (40 mg), and CuI (20 mg) were added to a solution of
2,6-diiodo-4-methylanisole (7) (1.00 g, 2.67 mmol) and 1 (409 mg,
(11) (a) Lavastre, O.; Ollivier, L.; Dixnuef, P. H.; Sibandhit, S.
Tetrahedron 1996, 52, 5495. (b) Godt, A. J . Org. Chem. 1997, 62, 7471.
(12) Ho¨ger, S.; Kukula, H. Unpublished.
(13) Wilkinson, J . H. J . Chem. Soc. 1951, 626.