Bulky trialkylsilyl acetylenes in the Cadiot-Chodkiewicz cross-coupling reaction

Article abstract of DOI:10.1021/jo025745x

Bulky trialkylsilyl-protected alkynes such as triethylsilyl (TES), tert-butyldimethylsilyl (TBS), and tri-isopropylsilyl (TIPS) acetylenes underwent the Cadiot-Chodkiewicz cross-coupling reaction with different bromoalkynes to form a variety of synthetically useful unsymmetrical diynes in good yields. The diyne alcohol 10 was transformed regio- and stereoselectively into enynes by hydrotelluration, carbometalation, and reduction reactions.

Full text of DOI:10.1021/jo025745x

SCHEME 1. Ap p r oa ch to In th om ycin C,
F r eelin gyn e, a n d E-En ed iyn e Alcoh ol Cor e
Bu lk y Tr ia lk ylsilyl Acetylen es in th e
Ca d iot-Ch od k iew icz Cr oss-Cou p lin g
Rea ction
J oseph P. Marino*,† and Hanh Nho Nguyen
Department of Chemistry, University of Michigan,
Ann Arbor, Michigan 48109
jmarino@nd.edu
Received March 21, 2002
Abstr a ct: Bulky trialkylsilyl-protected alkynes such as
triethylsilyl (TES), tert-butyldimethylsilyl (TBS), and tri-
isopropylsilyl (TIPS) acetylenes underwent the Cadiot-
Chodkiewicz cross-coupling reaction with different bro-
moalkynes to form a variety of synthetically useful unsym-
metrical diynes in good yields. The diyne alcohol 10 was
transformed regio- and stereoselectively into enynes by
hydrotelluration, carbometalation, and reduction reactions.
of Kedarcindin chromophore15 and C-1027 chromophore16
via a cross-coupling reaction of the vinylic telluride 2 with
dialkyl17 or dialkynyl18 zinc reagents, we decided to
employ the diyne alcohol 1 as a common precursor
(Scheme 1). This diyne alcohol 1 had been synthesized
in several steps with low overall yields by selective
protection of a carbon-carbon triple bond of penta-2,4-
diyn-1-ol19 or reacting the lithium anion of 1-trimethyl-
silyl-1,3-butadiyne with formaldehyde.20 However, both
penta-2,4-diyn-1-ol and 1-trimethylsilyl-1,3-butadiyne
intermediates were synthesized from the volatile and
explosive 1,3-butadiyne that rendered these synthetic
routes difficult. Conceivably, the diyne alcohol 1 could
be made by the acetylenic coupling21 with palladium-
copper catalyst systems22 or catalytic CuI/pyrrolidine23
conditions.
Unsymmetrical diynes are not only incorporated in
natural products (polyacetyelenes,1 epoxypolyynes,2 mon-
tipori acids,3 pellynols E-H,4 panaxydol,5 and (3R,8S)-
falcarindiol6) but they also provide important precursors
for the synthesis of enynes via regioselective hydrotel-
luration,7 hydroalumination with lithium aluminum hy-
dride,8 and carbometalation9 with alkyl10 and alkynyl11
Grignard reagents of the propargylic carbon-carbon
triple bond. In connection with our efforts to construct
the trisubstituted alkene 3 as a precursor of Inthomycin
C12 and Freelingyne,13 or the E-enediyne alcohol core14
4
† Current address: Department of Chemistry, University of Notre
Dame, Notre Dame, IN 46556-0069.
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2245. (c) Bohlmann, F.; Kleine, K. M.; Bornowski, H. Chem. Ber. 1965,
98, 369. (d) Bohlmann, F.; Hummel, H. C. Chem. Ber. 1970, 103, 3419.
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We envisioned that the diyne alcohol 1 could come from
the copper-catalyzed Cadiot-Chodkiewicz cross-coupling
reaction24-26 of a bromoalkyne 5 or 8 with a terminal
alkyne 6 or 7, respectively (Scheme 2). Walton27 and
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10.1021/jo025745x CCC: $22.00 © 2002 American Chemical Society
Published on Web 08/27/2002
J . Org. Chem. 2002, 67, 6841-6844
6841

TABLE 1. Un sym m etr ica l Diyn es Syn th esis
SCHEME 2. Differ en t Ap p r oa ch es to Diyn e
Alcoh ol
Vollhardt28 had performed the Cadiot-Chodkiewicz cross-
coupling reaction of the Type I using substrates similar
to 5 and 6. Encouraged by these results, we felt that a
trialkylsilyl acetylene 7 should undergo a similar cross-
coupling reaction with the 3-bromo-prop-2-yn-1-ol (8) to
afford the desired diyne alcohol 1 (Scheme 2, Type II)
under similar Cadiot-Chodkiewicz cross-coupling condi-
tions.
Resu lts a n d Discu ssion
We set out to synthesize 5-trialkylsilylpenta-2,4-diyn-
1-ol (1) by the Cadiot-Chodkiewicz cross-coupling reac-
tion catalyzed by CuCl and NH2OH‚HCl in a 30%
n-butylamine in water solvent (v/v; less basic compared
to the commonly used 70% ethylamine in water) between
3-bromo-prop-2-yn-1-ol (8), which is a known cross-
coupling partner,24,29,30 and a trialkylsilyl acetylene.
When trimethylsilyl acetylene was used, it decomposed
possibly via a desilylation path under the conditions
studied and no diyne product was obtained (Table 1,
entry 1), a result that had been observed by others when
using the standard solvent conditions.27,31 We switched
to triethylsilyl acetylene because it was more stable
toward hydrolysis (its hydrolysis rate in aqueous metha-
nolic alkali is 277 times slower).31 We anticipated that
the cross-coupling reaction would be much faster than
the competing desilylation reaction. As a matter of fact,
triethylsilyl acetylene underwent the cross-coupling reac-
tion cleanly with 3-bromoprop-2-yn-1-ol to afford the
diyne alcohol 10 in good yield (Table 1, entry 2). It was
necessary to maintain a sufficient amount of Cu(I) in the
aqueous amine solution.24,26 If the reaction turned blue
or green, immediate addition of hydroxylamine hydro-
chloride crystals during the reaction was necessary to
reduce Cu(II) to Cu(I) to avoid the homocoupling product
of the bromoalkyne.
With these results, other bromoalkynes in different
combinations with bulky trialkylsilyl-protected alkynes
were tested to determine the scope of this cross-coupling
reaction. Other bromoalkynes derived from 1,1-dimeth-
ylpropargyl alcohol (entry 3), N,N-dimethylpropargyl-
amine (entry 4), 1-hexyne (entry 5), and enynes (entries
6 and 7) underwent the cross-coupling reaction with
triethylsilyl acetylene in good yields. The reactions were
completed within 5 min for bromoalkynes containing
polar functional groups such as alcohols and amines
(entries 2-4 and 6). The insolubility of nonpolar bro-
moalkynes (entries 5 and 7) in the 30% aqueous n-
butylamine solution could be the reason the reaction
times were longer (20-30 min). A homocoupling product
was observed as a minor byproduct (entry 7).26 Under the
condition studied, the cross-coupling reaction between
triethylsilyl acetylene and a bromoalkyne derived from
ethyl propiolate gave a complex mixture of products.
Instead of TES, TBS (entries 8-12) and TIPS (entries
13-14) protecting groups were equally successful in the
cross-coupling reaction. Analogous to entry 7, homocou-
pling products were formed in 14% and 11% yields when
we used bromoalkynes derived from phenyl acetylene
(entry 11) and cyclohexenyl acetylene (entry 14), respec-
tively. It was advantageous to use tert-butyldimethylsilyl
acetylene (bp 49-51 °C at 55 mmHg)32 and triethylsilyl
acetylene (bp 136-138 °C at 760 mmHg,33 51-52 °C at
22 mmHg34) over triisopropylsilyl acetylene (bp 100 °C
at 20 mmHg)35 because excess amounts could be removed
under a reduced pressure. These high-yielding reactions
confirmed that both TBS and TIPS groups were stable
during the cross-coupling reaction. In addition to these
results, we also found that a thioacetylene, 1-ethylsul-
fanyl-4-methylbenzene also underwent the cross-coupling
reaction with bromoalkynes such as 3-bromoprop-2-yn-
1-ol (entry 15) and N,N-dimethyl(3-bromoprop-2-ynyl)-
amine (entry 16) in good yields.
The unsymmetrical diyne alcohol 10 could be selec-
tively functionalized at the propargylic carbon-carbon
(32) Schaumann, E.; Lindstaedt, J . Chem. Ber. 1983, 116, 1728-
1738 (in German).
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A.; Sverdlova, O. V.; Gindin, V. A. J . Gen. Chem. USSR (Engl. Transl.)
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Spyroudis, S.; Vollhardt, K. P. C. Angew. Chem., Int. Ed. Engl. 1987,
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2411.
6842 J . Org. Chem., Vol. 67, No. 19, 2002

TABLE 2. Ster eo- a n d Regioselective F u n ction a liza tion
of Diyn e Alcoh ol 10
were inert toward a variety of organometallic and reduc-
ing reagents that were very synthetically useful. These
silyl groups could be removed with fluoride sources at
-80 °C,39 0 °C,40 or room temperature41 and alkoxide at
room temperature.42
Exp er im en ta l Section
Gen er a l In for m a tion . All needles and syringes were oven-
dried and cooled to room temperature in a desiccator prior to
use. All reactions were carried out under a nitrogen (or argon)
atmosphere. Unless otherwise indicated, all starting materials
were used as received. n-Butyllithium, methylmagnesium bro-
mide, ethylmagnesium bromide, and vinylmagnesium bromide
came as a 2.5 M solution in tetrahydrofuran, a 3.0 M solution
in diethyl ether, a 3.0 M solution in diethyl ether, and a 1.0 M
solution in THF, respectively, and were titrated prior to use.1
Diethyl ether was dried over 4 Å molecular sieves and distilled
over Na/benzophenone. Silica gel, 40 µm, was purchased from
Scientific Absorbents Incorporated. TLC monitoring was best
with Hex:EtOAc solvent systems. The vinylic tellurides were
detected with a UV light, iodine, and a vanillin solution (27 mL
of H2O, 6 mL of concentrated H2SO4, 27 mL of MeOH and 1.2 g
of vanillin). Alcohols were best observed in a KMnO4 solution
(1.5 g of KMnO4, 10 g of K2CO3, 2.5 mL of 5% NaOH and 150
mL of water).
Infrared spectra (IR) were recorded on a FT-IR spectropho-
tometer with internal calibrations. Spectra were recorded either
from a neat oil between sodium chloride salt plates or from a
potassium bromide pellet. IR data were reported in wavenum-
bers (cm-1).
Proton nuclear magnetic resonance spectra (1H NMR) were
obtained on 300-, 400-, or 500-MHz FT NMR spectrometers.
Spectra were recorded in deuteriochloroform (CDCl3) with
residual proteo form as an internal reference or tetramethylsi-
lane (TMS) as the external reference. Data were reported as
follows: chemical shift (δ) in ppm (multiplicity, integrated
intensity, and coupling constant (J ) in hertz (Hz)). Abbreviations
to denote the multiplicity of a particular signal were s (singlet),
d (doublet), t (triplet), q (quartet), quint (quintet), sext (sextet),
m (multiplet), and br (broad).
triple bond. For instance, hydrotelluration of the diyne
alcohol 10 with (BuTe)2, and NaBH4 in ethanol afforded
three products such as the desired product 25 (7%), the
desilylated product of 25 (25%, desilylation of 25 occurred
most likely after the hydrotelluration reaction), and the
ditellurated product 26 (56%). After several attempts, we
found that the desired vinylic telluride 25 could be
obtained in high yield if the reaction was stopped after
20 min of reflux (Table 2, entry 1). When excess amounts
of (BuTe)2 and NaBH4 were used and with longer reaction
times, the ditellurated product 26 was formed predomi-
nantly (entry 2). In addition, we were also able to perform
the regio- and stereoselective carbometalation10,36 of the
diyne alcohol 10 with 2.5 equiv of methyl-, ethyl-, and
vinylmagnesium bromides in the presence of a catalytic
amount of CuI to afford enynes 27, 28, and 29, respec-
tively, in good yields (entries 3-5). Furthermore, lithium
aluminum hydride reduced the diyne alcohol 10 to enyne
30 regio- and stereoselectively in excellent yield (entry
6).8
In summary, our diyne approach utilizing bulky tri-
alkylsilyl protecting groups was very advantageous. First,
bulky trialkylsilyl acetylenes were stable under the
Cadiot-Chodkiewicz cross-coupling reaction. Second,
because of their much higher boiling points, these bulky
trialkylsilyl acetylenes were easier to synthesize and
handle than the commercially available but expensive
and volatile trimethylsilyl acetylene. In addition, both
the polar and nonpolar bromoalkynes were readily syn-
thesized from the corresponding alkynes via hypobromide
(Strauss method)24,29,37 or NBS/AgNO3(cat.)38 conditions.
In contrast, the preparation of bromotriethylsilyl acety-
lene could be difficult because it involved alkyllithium
reagents in the deprotonation step. Furthermore, in these
diynes having bulky trialkylsilyl protecting groups, the
more sterically hindered carbon-carbon triple bonds
Difference nuclear Overhauser effect (NOE) experiments were
performed on the 400- and 500-MHz FT NMR spectrometers
with automated programs.
Carbon-13 nuclear magnetic resonance spectra (13C NMR)
were obtained on 75-, 100-, or 125-MHz FT NMR spectrometers.
Spectra were recorded in deuteriochloroform with 77.0 ppm
resonance of deuteriochloroform as the internal reference.
High-resolution mass spectra (HRMS) were determined on a
VG 70-250S instrument by the University of Michigan, Depart-
ment of Chemistry Instrument Services Branch. Sample intro-
duction was via direct probe, and ionization was accomplished
by electron impact (EI) at 70 eV, by chemical ionization (CI) with
methane or ammonia, or by fast atom bombardment (FAB) with
sodium. Masses were reported in units of mass over charge (m/
z) to four decimal places in conjunction with the relative intensity
normalized to 100.
Gen er a l P r oced u r e for th e Diyn e Syn th esis. CuCl (0.06
mmol, 0.02 equiv) was added to a 30% n-BuNH2 (2.5 mL)
aqueous solution at room temperature that resulted in the
formation of a blue solution immediately. A few crystals of
hydroxylamine hydrochloride were added to discharge the blue
(39) Zapata, A. J .; Gu, Y.; Hammond, G. B. J . Org. Chem. 2000, 65,
227-234.
(36) Henaff, N.; Whiting, A. Tetrahedron 2000, 56, 5193-5204.
(37) (a) Volkov, A. N.; Skvortsov, Y. M.; Danda, I. I.; Shostakovskii,
M. F. J . Org. Chem. USSR (Engl. Transl.) 1970, 6, 903-907. (b)
Brandsma, L. In Preparative Acetylenic Chemistry, 2nd ed.; Elsevier:
Amsterdam, The Netherlands, 1988; pp 150-151. (c) Saalfrank, R. W.;
Welch, A.; Haubner, M.; Bauer, U. Liebigs Ann. 1996, 171-181. (d)
Strauss, F.; Follek, L.; Heyn, W. Berichte 1930, 63, 1868-1885.
(38) (a) Hofmeister, H.; Annen, K.; Laurent, H.; Wiechert, H. Angew.
Chem., Int. Ed. Engl. 1984, 23, 727-729. (b) Basak, S.; Srivastava,
S.; le Noble, W. J . J . J . Org. Chem. 1987, 52, 5095-5099.
(40) (a) Churcher, I.; Hallett, D.; Magnus, P. Tetrahedron 1999, 55,
1597-1606. (b) Choy, N.; Russell, K. C.; Alvarez, J . C.; Fider, A.
Tetrahedron Lett. 2000, 41, 1515-1518.
(41) (a) Kamikawa, T.; Hayashi, T. J . Org. Chem. 1998, 63, 8922-
8925. (b) Ma, C.; Yu, S.; Liu, X.; Cook, J . M. Tetrahedron Lett. 2000,
41, 2781-2785.
(42) (a) Nicolaou, K. C.; Murphy, F.; Barluenga, S.; Ohshima, T.;
Wei, H.; Xu, J .; Gray, D. L. F.; Baudoin, O. J . Am. Chem. Soc. 2000,
122, 3830-3838. (b) Raeppel, S.; Raeppel, F.; Suffert, J . Synlett 1998,
794-796.
J . Org. Chem, Vol. 67, No. 19, 2002 6843

color. The resulting colorless solution indicated the present of
Cu(I) salt. The alkyne (3.6 mmol, 1.2 equiv) was added to the
solution at room temperature forming a yellow acetylide suspen-
sion that was immediately cooled with an ice-water mixture.
The bromoalkyne (3 mmol, 1 equiv) was added at once and the
ice bath was removed (a small amount of diethyl ether could be
used in the transfer). More crystals of hydroxylamine hydro-
chloride were added throughout the reaction as necessary to
prevent the solution from turning blue or green. After several
additions of hydroxylamine hydrochloride crystals, the reaction
mixture had a rusty color (normally after 7 to 30 min, depending
on alkynyl substrates). At this point, the reaction was complete
according to TLC. The product was repeatedly extracted with
diethyl ether (3 × 20 mL), dried over MgSO4, and concentrated
under reduced pressure. The crude product could be purified
further by flash column chromatography on silica gel.
tography (90:10 Hex:EtOAc) afforded a yellow oil that was stored
in the freezer; yield 84%. 1H NMR (500 MHz, CDCl3 with 0.05%
v/v TMS) δ 5.63 (s, 1H), 4.11 (d, 2H, J ) 5.1 Hz), 1.92 (s, 3H),
1.51 (distorted t, 1H), 1.01 (t, 9H, J ) 7.8 Hz), 0.62 (q, 6H, J )
8.0 Hz); NOE (500 MHz, CDCl3 with 0.05% v/v TMS), the
carbinol hydrogens enhanced (0.6%) when the vinylic hydrogen
was irradiated; 13C NMR (100 MHz, CDCl3 with 0.05% v/v TMS)
δ 151.6, 105.2, 103.7, 96.1, 67.0, 16.8, 7.7, 4.7; IR (neat) 3340
(br), 2955, 2913, 2875, 2133, 1635, 1457, 1415, 1377, 1235, 1099,
1017, 723 cm-1; HRMS (EI, 70 eV) for C12H22O2Si [M+] calcd
210.1440, found 210.1444; m/z (rel intensity) 25 (33.6), 153 (57.2),
181 (100), 205 (21.6).
(E)-2-Eth yl-5-tr ieth ylsilylp en t-2-en -4-yn -1-ol (28): C13H24
-
OSi; FW ) 224; Rf ) 0.33 (80:20 Hex:EtOAc); a yellow oil, yield
80%; 1H NMR (300 MHz, CDCl3 with 0.05% v/v TMS) δ 5.58 (s,
1H), 4.15 (d, 2H, J ) 4.9 Hz), 2.38 (q, 2H, J ) 7.7 Hz), 1.82 (br
s, 1H), 1.06 (t, 3H, J ) 7.7 Hz), 1.00 (t, 9H, J ) 8.0 Hz), 0.62 (q,
6H, J ) 8.0 Hz); NOE (500 MHz, CDCl3 with 0.05% v/v TMS),
the carbinol hydrogens enhanced (0.2%) when the vinylic
hydrogen was irradiated; 13C NMR (125 MHz, CDCl3 with 0.05%
v/v TMS) δ 157.3, 104.6, 103.5, 96.1, 65.1, 24.3, 12.6, 7.6, 4.7;
IR (neat) 3327 (br), 2957, 2913, 2876, 2137, 1634, 1458, 1102,
1017, 724 cm-1; HRMS (DCI with ammonia) for C13H24OSi [M
+ H]+ calcd 225.1674, found 225.1669; CI with ammonia, m/z
(rel intensity) 132 (100), 225 (43.2).
5-Tr ieth ylsilylp en ta -2,4-d iyn -1-ol (10): C11H18OSi; FW )
194; Rf ) 0.32 (90:10 Hex:EtOAc). Column chromatography (90:
10 Hex:EtOAc) afforded a light yellow oil that was stored in the
freezer; yield 95%. 1H NMR (400 MHz, CDCl3 with 0.05% v/v
TMS) δ 4.30 (d, 2H, J ) 6.2 Hz), 1.75 (t, 1H, J ) 6.2 Hz), 0.95
(t, 9H, J ) 8.1 Hz), 0.58 (q, 6H, J ) 8.1 Hz); 13C NMR (100 MHz,
CDCl3 with 0.05% v/v TMS) δ 88.3, 86.1, 75.2, 71.1, 51.6, 7.5,
4.3; IR (neat) 3326 (br), 2957, 2937, 2877, 2224, 2107, 1458, 1414,
1236, 1018, 974, 798, 728 cm-1; HRMS (CI with NH3) for C11H18
-
OSi [M + NH4]+ cacld 212.1471, found 212.1460; CI with NH3,
m/z (rel intensity) 120 (40.3), 132 (100), 182 (71.3), 212 (74.5).
Hyd r otellu r a tion of Diyn e -Alcoh ol 10. To a solution of
(BuTe)2 (185 mg, 0.5 mmol, 0.5 equiv) in EtOH (30 mL) was
added solid NaBH4 (95 mg, 2.5 mmol, 2.5 equiv) portionwise
under nitrogen. The orange solution became light yellow. Diyne
alcohol (194 mg, 1 mmol, 1 equiv) was added to the reaction flask
under a nitrogen atmosphere. The reaction mixture was refluxed
for 30 min. Careful monitoring of the disappearance of the diyne
alcohol and the appearance of the monotelluration product (Rf
) 0.13 in 90:10 Hex:EtOAc, iodine detection) was required to
avoid the formations of the desilylated monotelluration and the
ditelluration products. The reaction was cooled to room temper-
ature and quenched with saturated aqueous NH4Cl. The product
was extracted with EtOAc, washed with brine, and dried over
MgSO4. The filtrate was concentrated under reduced pressure
and the residue was subjected to flash column chromatography
on silica gel (90:10 Hex:EtOAc). Yield 84%.
(Z)-2-(Bu t ylt e llu r o)-5-t r ie t h ylsilylp e n t -2-e n -4-yn -1-ol
(25): C15H28OSiTe; FW ) 382; Rf ) 0.13 (90:10 Hex:EtOAc).
Column chromatography (90:10 Hex:EtOAc) afforded a yellow
oil that was stored in the freezer; yield 84%. 1H NMR (400 MHz,
CDCl3 with 0.05% v/v TMS) δ 6.33 (t, 1H, J ) 1.8 Hz), 4.26 (dd,
2H, J ) 6.2, 1.5 Hz), 2.86 (t, 2H, J ) 7.7 Hz), 1.80-1.69 (m,
3H), 2.34 (sext, 2H, J ) 7.3 Hz), 0.97 (t, 9H, J ) 7.7 Hz), 0.86 (t,
3H, J ) 7.3 Hz), 0.60 (t, 6H, J ) 7.7 Hz); NOE (500 MHz, CDCl3
with 0.05% v/v TMS), the carbinol hydrogens enhanced (2.1%)
when the vinylic hydrogen was irradiated; 13C NMR (100 MHz,
CDCl3 with 0.05% v/v TMS) δ 136.3, 115.2, 105.1, 100.0, 69.1,
34.4, 25.3, 13.6, 7.8, 5.5, 4.5; IR (neat) 3350 (br), 2956, 2932,
2874, 2181, 2127, 1560, 1457, 1414, 1378, 1237, 1087, 1017, 726
cm-1; HRMS (CI with methane) for C15H28OSiTe [M + H]+ calcd
383.1050, found 383.1062; CI with ammonia, m/z (rel intensity)
132.1 (100), 197.1 (32.4), 381.1 (16.7).
(E)-5-Tr ieth ylsilyl-2-vin ylp en t-2-en -4-yn -1-ol (29): C13H22-
OSi; FW ) 222; Rf ) 0.15 (90:10 Hex:EtOAc); a yellow oil, yield
89%; 1H NMR (300 MHz, CDCl3 with 0.05% v/v TMS) δ 6.97
(dd, 1H, J ) 18.1, 11.3 Hz), 5.78 (m, 1H), 5.38 (d, 1H, J ) 17.9
Hz), 5.30 (dm, 1H, J ) 11.0 Hz), 4.35 (m, 2H), 2.16 (br s, 1H),
1.00 (t, 9H, J ) 7.7 Hz), 0.64 (q, 6H, J ) 7.7 Hz); NOE (500
MHz, CDCl3 with 0.05% v/v TMS), the carbinol hydrogens
enhanced (0.8%) when the vinylic hydrogen was irradiated; 13
C
NMR (125 MHz, CDCl3 with 0.05% v/v TMS) δ 148.7, 133.0,
116.9, 109.1, 103.1, 100.1, 62.6, 7.7, 4.6; IR (neat) 3336 (br), 3091,
2956, 2912, 2875, 2127, 1458, 1415, 1236, 1094, 1005, 911, 724
cm-1; HRMS (DCI with ammonia) for C13H22OSi [M + H]+ calcd
223.1518, found 223.1509; CI with ammonia, m/z (rel intensity)
120 (100), 223 (25.2); EI 70 eV, m/z (rel intensity) 45 (38.4), 75
(55.3), 103 (60.3), 137 (68.4), 165 (100), 193 (60.0), 251 (19.3).
Red u ction 3 of Diyn e Alcoh ol 10. Powdered LiAlH4 (35.6
mg, 0.9 mmol, 1.5 equiv) was added quickly to a solution of diyne
alcohol (121 mg, 0.6 mmol, 1 equiv) in 15 mL of diethyl ether at
0 °C. The reaction was warmed to room temperature and stirred
for 2 h. The reaction was cooled with an ice/water bath and
quenched with 2 N HCl until acidic. Saturated aqueous Na2-
SO4 was added and the reaction was stirred vigorously until a
bilayer was formed. The product was extracted with diethyl ether
several times, washed with brine, dried over MgSO4, and
concentrated under reduced pressure. The crude product (95%
yield) was pure enough to perform physical characterizations.
(E)-5-Tr ieth ylsilylp en t-2-en -4-yn -1-ol (30): C11H20OSi; FW
) 196; Rf ) 0.23 (80:20 Hex:EtOAc); a light yellow oil, 95% yield;
1H NMR (300 MHz, CDCl3 with 0.05% v/v TMS) δ 6.31 (dt, 1H,
J ) 15.9, 4.9 Hz), 5.79 (dm, 1H, J ) 15.9 Hz), 4.18 (dd, 2H, J )
5.2, 1.9 Hz), 1.83 (br s, 1H), 0.99 (t, 9H, J ) 8.0 Hz), 0.62 (q, 6H,
J ) 8.0 Hz); 13C NMR (125 MHz, CDCl3 with 0.05% v/v TMS) δ
143.1, 110.8, 104.4, 93.0, 63.1, 7.7, 4.6; IR (neat) 3326 (br), 2955,
2912, 2876, 2175, 2133, 1938, 1630, 1458, 1415, 1378, 1236,
1083, 1008, 954, 724 cm-1; HRMS (DCI with ammonia) for [M
+ H]+ for C11H20OSi calcd 197.1362, found 197.1355; CI with
ammonia, m/z (rel intensity) 132 (100), 186 (23.7), 197 (39.1);
EI 70 eV, m/z (rel intensity) 75 (44.2), 103 (62.8), 139 (85.7),
167 (100), 205 (26.1).
Gen er a l P r oced u r e for th e Ca r bom eta la tion s2 of Diyn e
Alcoh ol 10. Methyl-, ethyl-, or vinylmagnesium bromide (7.5
mmol, 2.5 equiv) was added to a suspension of CuI (0.3 mmol,
0.1 equiv) and Et2O (20 mL) at 0 °C. A dark brown solution
formed immediately. To this solution was added a solution of
diyne -alcohol 10 (3 mmol, 1 equiv) in 2 mL of Et2O at 0 °C. The
ice-bath was removed and the reaction was stirred overnight.
The reaction was quenched slowly at 0 °C with 2 N HCl under
nitrogen until the reaction mixture was acidic. The product was
extracted with diethyl ether, washed with brine, dried over
MgSO4, and concentrated under reduced pressure. The crude
product was pure enough for characterizations. Only the E-
isomer was detected in the crude 1H NMR.
Ack n ow led gm en t. This work was supported by the
University of Michigan.
Su p p or tin g In for m a tion Ava ila ble: Sample procedure
for the Cadiot-Chodkiewicz cross-coupling reaction, proce-
dures for regio- and stereoselective transformations of diyne
alcohol 10, and characterization data (1H NMR, 13C NMR,
FTIR, and HRMS) for all compounds. This material is avail-
able free of charge via the Internet at http://pubs.acs.org.
(E)-2-Meth yl-5-tr ieth ylsilylpen t-2-en -4-yn -1-ol (27): C12H22
-
OSi; FW ) 210; Rf ) 0.26 (85:15 Hex:EtOAc). Column chroma-
J O025745X
6844 J . Org. Chem., Vol. 67, No. 19, 2002