Synthesis of skipped enynes via phosphine-promoted couplings of propargylcopper reagents

Article abstract of DOI:10.1016/j.tet.2003.04.002

An electron-rich phosphine additive is critical and sufficient for propargyl-selective couplings of propargylcopper reagents and alkenyl halides. This method is complementary to those previously described, in which high allenyl selectivity is observed in

Full text of DOI:10.1016/j.tet.2003.04.002

Tetrahedron 59 (2003) 8913–8917
Synthesis of skipped enynes via phosphine-promoted couplings of
propargylcopper reagents
*
Timothy P. Heffron, James D. Trenkle and Timothy F. Jamison
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139, USA
Received 31 March 2003; accepted 8 April 2003
Abstract—An electron-rich phosphine additive is critical and sufficient for propargyl-selective couplings of propargylcopper reagents and
alkenyl halides. This method is complementary to those previously described, in which high allenyl selectivity is observed in analogous
coupling reactions. While the basis of the phosphine effect requires further investigation, the information gained in these studies enables the
synthesis of complex molecules by way of skipped enyne intermediates.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
stannanes also undergo propargyl-selective carbonyl
addition. In related work, chiral allenylzinc species can be
prepared in high ee from chiral propargyl mesylates, and
subsequent 1,2-addition to achiral and chiral aldehydes can
be effected with high diastereoselectivity.3
We recently reported that the only carbon–carbon bond-
forming reaction required for the preparation of ladder
polyether subunits was a propargylcopper–alkenyl iodide
coupling process (Scheme 1).1 The selectivity for the
desired skipped enynes (e.g. A) over allenyl-coupled
products (B) was generally 85:15 when 4-DMAP was
used as an additive. Herein we report a full account of our
development of an improved process, in which Bu3P
provides maximum yield and selectivity (.95:5 propargyl/
allenyl).
Prior to these carbonyl addition processes, Corey pioneered
propargyl-selective alkylation and allylation of propargyl-
copper reagents,4 and Ganem later reported the first
propargyl-selective conjugate additions of these species.5
Danheiser’s allenylsilane reagents generally favor (tri-
methylsilyl)cyclopentene annulation in analogous
reactions,6 whereas Haruta showed that certain allenyl-
stannanes were selective for 1,4-SE20 addition, affording
4-alkynylcarbonyl compounds.7
The development of propargyl-selective cross-coupling
methods, however, is much less developed. In a series of
recent investigations, Ma observed that Pd-catalyzed cross-
coupling of allenylzinc reagents and alkenyl iodides favored
the allenyl regioisomer unless the electrophile contained an
electron-withdrawing group.8 Since allenyl coupling was
generally favored in cases closest to those for which we
required high propargyl selectivity, the starting point for
these investigations was a singular example of selective
propargyl-sp2 coupling described by Normant in 1975.9
Preparation of an organocopper reagent involved deproto-
nation of 1-(trimethylsilyl)-1-propyne with n-BuLi in
TMEDA/THF, addition of CuI, removal of the THF in
vacuo, and addition of pyridine. An explanation for the
solvent switch was not provided, but we reasoned that
modification of the organocopper species by interaction
with pyridine might be necessary for maximum yield of the
propargyl-coupled product. In this vein, we examined a
variety of additives with the aim of duplicating this high
Scheme 1.
The development of carbon–carbon bond forming reactions
that favor propargyl-coupled products where allenyl-
derived adducts are also possible has received much
attention. Danheiser demonstrated that high propargyl
selectivity is obtained in additions of allenylsilane reagents
to carbonyl groups and oxocarbenium ions,2 and Marshall
found that chiral, enantiomerically enriched allenyl-
Keywords: phosphine; enyne intermediates; organocopper; propargylation.
*
Corresponding author. Tel.: þ1-617-253-2135; fax: þ1-617-258-7500;
e-mail: tfj@mit.edu
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.04.002

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T. P. Heffron et al. / Tetrahedron 59 (2003) 8913–8917
propargyl selectivity while simultaneously obviating the
solvent exchange.
Table 2. Propargyl-selective coupling of alkenyl iodides 1a–i
Entry
Iodide
R1
R2
R3
2:3a
Yield (%)
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
n-Bu
TBSOCH2
HO(CH2)3
(see below)
H
n-Pr
Ph
Me3Si
Me3Si
Me3Si
Me3Si
n-Pr
n-Pr
H
H
H
H
H
n-Pr
H
Me
H
.20:1
.20:1
.20:1
.20:1
n.d.
.20:1
.20:1
.20:1
.20:1
81
45
67
67
, 5
33b
80
38
52
2. Results and discussion
As summarized in Scheme 2 and Table 1, we found that
several additives had dramatically different effects upon
both yield and propargyl/allenyl selectivity in our initial
investigations with alkenyl iodide 1a, which was prepared by
hydroalumination/iodination (DIBAL-H; I2). Although
propargyl selectivity was high in reactions conducted in
THF, they were not of preparative utility (entry 2). Nitrogen-
and sulfur-containing additives were either efficacious or
selective, but not both(entries 3–6). Organophosphines onthe
other hand (entries 7–9) displayed very high levels of
propargyl selectivity, and of these, tributylphosphine (Bu3P)
also gave the desired product in good yield.
n-Bu
H
H
H
n-Bu
See Scheme 2 and Section 4 for details.
a
1
Determined by H NMR analysis of unpurified product mixture.
NMR analysis of the unpurified product mixture indicated a 2:1 mixture
of iodide 1f and product 2f, i.e. conversion was approximately 33%. The
yield reported (33%) is the isolated yield based on a theoretical 100% and
therefore is nearly quantitative based on conversion.
b
is observed in entry 4 with skipped diene 1d. A
trimethylsilyl group geminal to the iodine atom is not
required for efficacy or selectivity, as shown by entries 5–9.
In one case, subsitution cis to the iodide significantly
reduces the efficiency of coupling (entry 5). Nevertheless,
conjugated alkenyl iodides couple smoothly, as demon-
strated by (E)-1-iodo-2-phenylpropene (entry 7). Finally,
the coupling is stereospecific with respect to olefin geometry
(entries 8 and 9).
Scheme 2.
Table 1. Effects of additives upon yield and selectivity in coupling
reactions of alkenyl iodide 1a
Entry
Solvent
Additive
2a:3aa
Isolated yield of 2a (%)
3. Conclusions
1
2
3
4
5
6
7
8
9
Ether
THF
THF
THF
THF
THF
THF
THF
THF
None
None
Pyridine
4-DMAP
Et3N
Me2S
Ph3P
Bu3P
n.d.
,5
37
47
69
39
33
41
81
41
.20:1
10:1
7:1
10:1
20:1
.20:1
.20:1
.20:1
In summary, an electron-rich phosphine additive is critical
and sufficient for propargyl-selective couplings of pro-
pargylcopper reagents and alkenyl halides. This method is
complementary to that reported by Ma, who observed
propargyl selectivity in couplings with electron-deficient
alkenyl halides and high allenyl selectivity with electron-
rich coupling partners, the latter representing those in which
we observe high propargyl selectivity. Application of the
information gained in these studies to the synthesis of
complex molecules and further investigation of the basis of
propargyl selectivity are ongoing in our laboratories.
Cy3P
Perfomed on 2 g scale (7.1 mmol of iodide 1a). See Scheme 2 and Section 4
for details.
a
Determined by 1H NMR analysis of unpurified product mixture.
Several explanations for the higher yield and selectivity
imparted by Bu3P are possible, including increased
solubility and/or thermal stability of the organocopper
species, or a change in its aggregation state.10,11 Since
higher yields are observed with the more electron-rich Bu3P
than with Ph3P (entries 7 and 8), it is possible that oxidative
addition into the carbon–iodine bond is accelerated by the
former. Nevertheless, the results with Cy3P (entry 9) might
suggest otherwise, unless the increased steric demand of this
phosphine is responsible for the reduction in yield.
4. Experimental
4.1. General information
Unless otherwise noted, all reactions were performed under
an oxygen-free atmosphere of argon with rigid exclusion of
moisture from reagents and glassware. Tetrahydrofuran
(THF) and Et2O were distilled from a blue solution of
sodium benzophenone ketyl. Dimethylformamide (DMF)
was used as supplied by Aldrich (99.8% anhydrous; stored
over molecular sieves). Analytical thin layer chromato-
graphy (TLC) was performed using EM Science silica gel
60 F254 plates. The developed chromatogram was analyzed
by UV lamp (254 nm) and ethanolic phosphomolybdic acid
The scope of this transformation with respect to the
substitution pattern and nature of the alkenyl iodide was
also evaluated (Table 2). In all cases, the desired propargyl-
coupled product is formed exclusively (.20:1, H NMR).
Protected (entry 2) and free hydroxyl groups (entries 3 and
4) are tolerated, and significantly, no p-bond isomerization
1

T. P. Heffron et al. / Tetrahedron 59 (2003) 8913–8917
8915
(PMA) or aqueous potassium permanganate (KMnO4).
Liquid chromatography was performed using a forced
flow (flash chromatography) of the indicated solvent system
on Silicycle Silica Gel (230–400 mesh).12 1H and 13C NMR
spectra were recorded in CDCl3 on a Varian Inova 500 MHz
spectrometer. Chemical shifts in 1H NMR spectra are
reported in parts per million (ppm) on the d scale from an
internal standard of residual chloroform (7.27 ppm). Data
are reported as follows: chemical shift, multiplicity (s¼
singlet, d¼doublet, t¼triplet, q¼quartet, m¼multiplet,
app¼apparent, and br¼broad), coupling constant in hertz
(Hz), and integration. Chemical shifts of 13C NMR spectra
are reported in ppm from the central peak of CDCl3
(77.2 ppm) on the d scale. Infrared (IR) spectra were
recorded on a Perkin–Elmer 2000 FT-IR. High Resolution
mass spectra (HR-MS) were obtained on a Bruker
Daltonics APEXII 3 Tesla Fourier Transform Mass
Spectrometer by Dr Li Li of the Massachusetts Institute of
Technology Department of Chemistry Instrumentation
Facility.
(ESI) calcd for C12H27IOSi2 (MþNa)þ 393.0537, found
393.0534.
4.2.3. (4E)-5-Iodo-5-trimethylsilanyl-pent-4-en-1-ol (1c).
To a solution of 5-trimethylsilanyl-pent-4-yn-1-ol14 (12.2 g,
77.8 mmol) in Et2O (190 mL) at 08C was added a 1 M
solution of DIBAL-H in hexane (190 mL). The resulting
solution was heated 24 h at reflux. This solution was then
cooled to 2788C, diluted with Et2O (60 mL), and a solution
of I2 (79 g, 310 mmol) in Et2O (175 mL) was added. After
stirring for 2 h at 2788C, the reaction was quenched by
pouring into 1 M HCl (200 mL) and ice (40 g). The maroon
organic layer was separated, and the aqueous layer was
extracted with Et2O (3£200 mL). The combined organic
layers were washed with saturated Na2S2O3, brine, dried
over MgSO4, and concentrated in vacuo. The crude product
was purified by column chromatography (20% EtOAc in
hexane) to yield the vinyl iodide as a pale yellow oil (20.1 g,
91%, .95% E): Rf 0.20 (20% EtOAc in hexane); IR (thin
film, NaCl) 3335, 2952, 1588, 1407, 1249, 1059, 841 cm21
;
1H NMR (500 MHz, CDCl3) d 7.18 (t, J¼7.9 Hz, 1H), 3.66
(t, J¼6.4 Hz, 2H), 2.18 (dt, J¼7.7, 7.6 Hz, 2H), 1.67 (m,
2H), 0.28 (s, 9H); 13C NMR (125 MHz, CDCl3) d 155.7,
107.6, 62.2, 32.2, 31.7, 1.4; HR-MS (ESI) calcd for
C8H17IOSi (M)þ 284.0088, found 284.0091.
4.2. Synthesis of Vinyl Iodides 1a–1i
4.2.1. [(1E)1-Iodo-hex-1-enyl]-trimethyl-silane (1a).
Synthesized according to a reported procedure.13
4.2.2. (1E)-3-(tert-Butyl-dimethyl-silanyloxy)-1-iodo-1-
trimethylsilanyl-propene (1b). To a solution of 3-tri-
methylsilanyl-prop-2-yn-1-ol6b (8.0 g, 62.5 mmol) in Et2O
(160 mL) was added a 1 M solution of DIBAL-H in hexane
(156 mL). The resulting solution was heated 24 h at reflux.
This solution was then cooled to 2788C, diluted with Et2O
(60 mL), and a solution of I2 (63.5 g, 250 mmol) in Et2O
(200 mL) was added. After stirring for 2 h at 2788C, the
reaction was quenched by pouring into 1 M HCl (100 mL)
and ice (50 g). The maroon organic layer was separated, and
the aqueous layer was extracted with Et2O (3£150 mL). The
combined organic layers were washed with saturated
Na2S2O3, brine, dried over MgSO4, and concentrated in
vacuo. The crude product was purified by column
chromatography (20% EtOAc in hexane) to yield the
vinyl iodide as a pale yellow oil (10.7 g, 67%, .95% E):
Rf 0.35 (20% EtOAc in hexane); IR (thin film, NaCl) 3312,
2955, 1250, 1018, 842 cm21; 1H NMR (500 MHz, CDCl3) d
7.35 (t, J¼7.0 Hz, 1H), 4.09 (dd, J¼7.0, 6.1 Hz, 2H), 0.29
(s, 9H); 13C NMR (125 MHz, CDCl3) d 154.3, 111.6, 63.6,
1.2; HR-MS (ESI) calcd for C6H13IOSi (MþNa)þ
278.9673, found 278.9681.
4.2.4. (2Z, 5E)-6-Iodo-3,6-bis-trimethylsilanyl-hexa-2,5-
dien-1-ol (1d). To a solution of 2b (see below; 9.6 g,
24.6 mmol) in Et2O (60 mL) was added a 1 M solution of
DIBAL-H in hexane (60 mL). The resulting solution was
heated 24 h at reflux. This solution was then cooled to
2788C, diluted with Et2O (50 mL), and a solution of I2
(25 g, 98.4 mmol) in Et2O (150 mL) was added. After
stirring for 2 h at 2788C, the reaction mixture was warmed
to 08C and stirred 1 h, warmed to room temperature and
stirred 40 min, then quenched by pouring into 1 M HCl
(200 mL) and ice (70 g). The maroon organic layer was
separated, and the aqueous layer was extracted with Et2O
(3£250 mL). The combined organic layers were washed
with saturated Na2S2O3, brine, dried over MgSO4, and
concentrated in vacuo. The crude product was purified by
column chromatography (20% EtOAc in hexane) to yield
the vinyl iodide as a pale yellow oil (5.6 g, 55%, .95% E):
Rf 0.28 (20% EtOAc in hexane); IR (thin film, NaCl) 3324,
2954, 1250, 839 cm21; 1H NMR (500 MHz, CDCl3) d 7.10
(t, J¼7.6 Hz, 1H), 6.14 (tt, J¼7.0, 1.5 Hz, 1H), 4.23 (dd,
J¼6.7, 5.8 Hz, 2H), 2.87 (dd, J¼7.6, 1.5 Hz, 2H), 0.27 (s,
9H), 0.17 (s, 9H); 13C NMR (125 MHz, CDCl3) d 154.4,
141.5, 141.4, 108.0, 62.3, 41.9, 1.2, 0.3; HR-MS (ESI) calcd
for C12H29IOSi2 (MþNa)þ 391.0381, found 391.0394.
To a solution of this vinyl iodide (5.1 g, 20.0 mmol) in DMF
(20 mL) was added imidazole (1.9 g, 28.0 mmol), and
TBSCl (4.2 g, 28.0 mmol). The reaction mixture was
allowed to stir overnight at room temperature and
was quenched with water (100 mL). The aqueous layer
was extracted with Et2O (3£50 mL). The combined organic
layers were washed with brine, dried over MgSO4, and
concentrated in vacuo to yield the protected alcohol (6.8 g,
92%) without the need for further purification: Rf 0.45 (5%
EtOAc in hexane); IR (thin film, NaCl) 3853, 2955, 2929,
4.2.5. (4Z)-4-Iodo-oct-4-ene (1e). Synthesized according to
a reported procedure.15 NMR spectral data were consistent
with that reported.16
4.2.6. (4E)-4-Iodo-oct-4-ene (1f). To a solution of Cp2-
ZrHCl (22.0 g, 87.1 mmol) in CH2Cl2 (360 mL) was added
4-octyne (8.0 g, 72.6 mmol) and the reaction mixture stirred
overnight. The mixture was cooled to 08C, iodine (20.3 g,
80.0 mmol) was added and the reaction was warmed to
room temperature, stirred 1 h then quenched by pouring into
1 M HCl (200 mL) and ice (50 g). The organic layer was
separated, and the aqueous layer was extracted with CH2Cl2
1
2857, 1251, 1098, 838, 776 cm21; H NMR (500 MHz,
CDCl3) d 7.25 (t, J¼6.0 Hz, 1H), 4.11 (d, J¼6.5 Hz, 2H),
0.90 (s, 9H), 0.27 (s, 9H), 0.07 (s, 6H); 13C NMR (125 MHz,
CDCl3) d 156.2, 109.0, 64.6, 26.6, 19.0, 1.6, 24.4; HR-MS

8916
T. P. Heffron et al. / Tetrahedron 59 (2003) 8913–8917
1
(3£150 mL). The combined organic layers were washed
with saturated Na2S2O3, brine, dried over MgSO4, and
concentrated in vacuo. The crude product was purified by
column chromatography (hexane) to yield 1f as a pale
yellow oil (9.3 g, 54%, .95% E). NMR spectral data were
consistent with that reported.16
2873, 2176, 1250, 843, 760 cm21; H NMR (500 MHz,
CDCl3) d 5.46 (br t, J¼7.3 Hz, 1H), 2.94 (d, J¼1.2 Hz, 2H),
2.07 (t, J¼7.6 Hz, 2H), 2.01 (app q, J¼7.3 Hz, 2H), 1.45–
1.34 (m, 4H), 0.91 (app q, J¼7.6 Hz, 6H), 0.17 (s, 9H) 13C
NMR (125 MHz, CDCl3) d 133.7, 126.9, 105.3, 87.0, 32.6,
30.1, 27.9, 23.2, 21.6, 14.3, 14.1, 0.3; HR-MS (EI) calcd for
C14H26Si (M)þ 222.1798, found 222.1801.
4.2.7. [(1E)-2-Iodo-1-methyl-vinyl]-benzene (1g). Syn-
thesized according to a reported procedure.17
4.3.4. Trimethyl-[(4E)-5-phenyl-hex-4-en-1-ynyl]-silane
(2g). Rf 0.41 (5% EtOAc in hexane); IR (thin film, NaCl)
1
4.2.8. (1Z)-1-Iodo-hex-1-ene (1h). Synthesized according
to a reported procedure.18 NMR spectral data were
consistent with those reported.19
2960, 2931, 2873, 2176, 1249, 842, 759 cm21; H NMR
(500 MHz, CDCl3) d 7.41–7.24 (m, 5H), 5.80 (tq, J¼6.1,
1.2 Hz, 1H), 3.17 (d, J¼6.7 Hz, 2H), 2.05 (br s, 3H), 0.17 (s,
9H); 13C NMR (125 MHz, CDCl3) d 143.3, 136.9, 128.5,
127.2, 126.0, 122.5, 105.3, 84.7, 26.6, 20.1, 0.4; HR-MS
(ESI) calcd for C15H20Si (MþH)þ 229.1407, found
229.1407.
4.2.9. (1E)-1-Iodo-hex-1-ene (1i). Synthesized according to
a reported procedure.20
4.3. Representative procedure for the propargyl/allenyl
coupling of vinyl iodides 1a–b, 1e–i
4.3.5. (4Z)-Trimethyl-non-4-en-1-ynyl-silane (2h). Rf
0.32 (hexane); IR (thin film, NaCl) 2959, 2929, 2177,
1250, 842, 760 cm21; 1H NMR (500 MHz, CDCl3) d 5.51–
5.38 (m, 2H), 2.99 (d, J¼6.4 Hz, 2H), 2.05 (app q,
J¼6.4 Hz, 2H), 1.38–1.28 (m, 4H), 0.89 (t, J¼7.0 Hz,
3H), 0.16 (s, 9H); 13C NMR (125 MHz, CDCl3) d 132.2,
124.0, 105.7, 84.2, 31.7, 27.1, 22.6, 18.6, 14.2, 0.3; HR-MS
(EI) calcd for C12H22Si (M2CH3)þ 179.1251, found
179.1252.
A
solution of 1-trimethylsilyl-1-propyne (1.5 mL,
10.0 mmol) in THF (21.4 mL) was cooled to 2788C and
was treated with a 2.5 M solution of n-BuLi (4.6 mL) and
TMEDA (1.7 mL, 11.4 mmol). The solution was allowed to
warm to 08C and stirred 45 min. The solution was then
transferred via cannula to a 2788C slurry of CuI (2.3 g,
12.1 mmol) in THF (28.6 mL) and stirred at that tempera-
ture 30 min. Then the additive (10.0 mmol) was introduced
and the solution was allowed to warm to 2208C. At that
time the vinyl iodide (7.1 mmol) was added, the reaction
mixture was allowed to warm to room temperature
gradually and stirred overnight. The reaction was quenched
with 1 M HCl (50 mL), and the organic layer was separated.
The aqueous layer was extracted with Et2O (3£200 mL).
The combined organic layers were washed with water,
brine, dried over MgSO4, and concentrated in vacuo. The
allenyl/propargyl ratio of the coupled products was
determined by 1H NMR analysis of the crude material.
The crude product was then purified by column chroma-
tography (hexane).
4.3.6. (4E)-Trimethyl-non-4-en-1-ynyl-silane (2i). Rf 0.24
(hexane); IR (thin film, NaCl) 2959, 2927, 1250, 842,
760 cm21; 1H NMR (500 MHz, CDCl3) d 5.68 (dt, J¼15.3,
7.0 Hz, 1H), 5.39 (dt, J¼15.0, 5.5 Hz, 1H), 2.95 (d,
J¼5.5 Hz, 2H), 2.03 (app q, J¼6.1 Hz, 2H), 1.39–1.29
(m, 4H), 0.90 (t, J¼7.0 Hz, 3H), 0.17 (s, 9H); 13C NMR
(125 MHz, CDCl3) d 132.2, 124.0, 105.7, 84.2, 31.7, 27.1,
22.6, 18.6, 14.2, 0.3; HR-MS (EI) calcd for C12H22Si (M)þ
194.1485, found 194.1491.
4.4. Representative procedure for the propargyl/allenyl
coupling of vinyl iodides 1c–d
4.3.1. (4Z)-1,4-Bis-trimethylsilanyl-non-4-en-1-yne (2a).
Rf 0.31 (hexane); IR (thin film, NaCl) 2958, 2859, 2174,
1618, 1466, 1420, 1250, 1054, 1010, 841, 759, 695,
A solution of 1-trimethylsilyl-1-propyne (1.0 mL,
6.5 mmol) in THF (4.3 mL) was cooled to 2788C and was
treated with a 2.5 M solution of n-BuLi (2.7 mL) and
TMEDA (1.0 mL, 6.7 mmol). The solution was allowed to
warm to 08C and stirred 45 min. The solution was then
transferred via cannula to a 2788C slurry of CuI (1.4 g,
7.2 mmol) in THF (5.7 mL) and stirred at that temperature
30 min. Then PBu3 (1.6 mL, 6.5 mmol) was introduced and
the solution was allowed to warm to 2208C. At that time the
vinyl iodide (1.4 mmol) was added, the reaction mixture
was allowed to warm to room temperature gradually and
stirred overnight. The reaction was quenched with 1 M HCl
(20 mL), and the organic layer was separated. The aqueous
layer was extracted with Et2O (3£20 mL). The combined
organic layers were washed with water, brine, dried over
MgSO4, and concentrated in vacuo. The crude product was
purified by column chromatography (20% EtOAc in
hexane).
642 cm21
;
1H NMR (500 MHz, CDCl3) d 6.24 (t,
J¼7.6 Hz, 1H), 2.98 (s, 2H), 2.14 (app q, J¼13.7, 6.4 Hz,
2H), 1.36 (m, 4H), 0.92 (t, J¼6.7 Hz, 3H), 0.18 (s, 9H), 0.16
(s, 9H); 13C NMR (125 MHz, CDCl3) d 144.4, 132.7, 106.3,
87.6, 32.3, 31.8, 28.9, 22.7, 14.3, 0.4, 0.3; HR-MS (ESI)
calcd for C15H30Si2 (MþNa)þ 289.1778, found 289.1773.
4.3.2. (4Z)-6-(tert-Butyl-dimethyl-silanyloxy)-1,4-bis-tri-
methylsilanyl-hex-4-en-1-yne (2b). Rf 0.41 (5% EtOAc in
1
hexane); IR (thin film, NaCl) cm21; H NMR (500 MHz,
CDCl3) d 6.36 (tt, J¼6.4, 1.5 Hz, 1H), 4.27 (tt, J¼6.2,
1.2 Hz, 2H), 3.02 (br d, J¼1.5 Hz, 2H), 0.91 (s, 9H), 0.17 (s,
9H), 0.16 (s, 9H), 0.09 (s, 6H); 13C NMR (125 MHz,
CDCl3) d 143.8, 135.2, 105.7, 88.7, 63.3, 29.1, 26.7, 19.1,
0.8, 0.6, 24.3; HR-MS (ESI) calcd for C18H38OSi3
(MþNa)þ 377.2123, found 377.2124.
4.4.1. 5,8-Bis-trimethylsilanyl-oct-4-en-7-yn-1-ol (2c). Rf
0.41 (20% EtOAc in hexane); IR (thin film, NaCl) 3314,
4.3.3. Trimethyl-[(4E)-4-propyl-oct-4-en-1-ynyl]-silane
(2f). Rf 0.39 (hexane); IR (thin film, NaCl) 2960, 2932,
2956, 2898, 2173, 1618, 1420, 1249, 1053, 841, 759 cm21
;

T. P. Heffron et al. / Tetrahedron 59 (2003) 8913–8917
8917
1H NMR (500 MHz, CDCl3): d 6.24 (t, J¼7.6 Hz, 1H), 3.68
(t, J¼6.4 Hz, 2H), 2.99 (s, 2H), 2.24 (dt, J¼7.6, 7.3 Hz, 2H),
1.68 (m, 2H), 0.19 (s, 9H), 0.16 (s, 9H); 13C NMR
(125 MHz, CDCl3) d 143.6, 134.5, 106.5, 88.3, 63.3, 33.5,
29.4, 28.9, 0.8, 0.7; HR-MS (ESI) calcd for C14H28OSi2
(MþNa)þ 291.1571, found 291.1577.
3. (a) Marshall, J. A. Chem. Rev. 1996, 96, 31. (b) Marshall, J. A.
Chem. Rev. 2000, 100, 3163. see also (c) Tamaru, Y.; Goto, S.;
Tanaka, A.; Shimizu, M.; Kimura, M. Angew. Chem. Int. Ed.
1996, 35, 878.
4. Corey, E. J.; Kirst, H. A. Tetrahedron Lett. 1968, 5041.
5. Ganem, B. Tetrahedron Lett. 1974, 4467.
6. (a) Danheiser, R. L.; Carini, D. J.; Basak, A. J. Am. Chem. Soc.
1981, 103, 1604. (b) Danheiser, R. L.; Carini, D. J.; Fink,
D. M.; Basak, A. Tetrahedron 1983, 39, 935. see also
(c) Danheiser, R. L.; Dixon, B. R.; Gleason, R. W. J. Org.
Chem. 1992, 57, 6094.
4.4.2. (2Z, 5Z)-3,6,9-Tris-trimethylsilanyl-nona-2,5-dien-
8-yn-1-ol (2d). Rf 0.42 (20% EtOAc in hexane); IR (thin
film, NaCl) 3313, 2956, 2898, 2173, 1249, 839 758 cm21
;
1H NMR (500 MHz, CDCl3) d 6.23 (tt, J¼7.3, 1.5 Hz, 1H),
6.13 (tt, J¼7.0, 1.5 Hz, 1H), 4.22 (d, J¼7.0 Hz, 2H), 3.02
(d, J¼1.2 Hz, 2H), 2.96 (dd, J¼7.3, 1.2 Hz, 2H), 0.19 (s,
9H), 0.17 (s, 9H), 0.16 (s, 9H); 13C NMR (125 MHz,
CDCl3) d 143.1, 141.9, 140.9, 134.5, 105.8, 87.9, 62.4, 39.1,
28.8, 0.49, 0.43, 0.20; HR-MS (ESI) calcd for C18H36OSi3
(MþNa)þ 375.1966, found 375.1964.
7. (a) Haruta, J.; Nishi, K.; Matsuda, S.; Tamura, Y.; Kita, Y.
J. Chem. Soc., Chem. Commun. 1989, 1065. (b) Haruta, J.;
Nishi, K.; Matsuda, S.; Akai, S.; Tamura, Y.; Kita, Y. J. Org.
Chem. 1990, 55, 4853.
8. (a) Ma, S.; Zhang, A. J. Org. Chem. 1998, 63, 9601. (b) Ma, S.;
Zhang, A.; Yu, Y.; Xia, W. J. Org. Chem. 2000, 65, 2287.
(c) Ma, S.; Zhang, A. J. Org. Chem. 2002, 67, 2287.
9. Commercon, A.; Normant, J.; Villieras, J. J. Organomet.
Chem. 1975, 93, 415.
Acknowledgements
10. Whitesides, G. W.; Casey, C. P.; Krieger, J. K. J. Am. Chem.
Soc. 1971, 93, 1379.
We thank Johnson and Johnson for a research assistantship
to T. P. H. We also thank the National Institute of General
Medical Sciences (GM-063755), the NSF (CAREER CHE-
0134704), Merck Research Laboratories, Johnson and
Johnson, Boehringer-Ingelheim, Pfizer, 3M, The Donors
of the Petroleum Research Fund, and MIT for financial
support. The NSF (CHE-9809061 and DBI-9729592) and
NIH (1S10RR13886-01) provide partial support for the MIT
Department of Chemistry Instrumentation Facility.
11. Corey, E. J.; Beames, D. J. J. Am. Chem. Soc. 1972, 94, 7210.
12. Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923.
13. Zweifel, G.; Murray, R. E. J. Org. Chem. 1981, 46, 1292.
14. Cruciani, P.; Stammler, R.; Aubert, C.; Malacria, M. J. Org.
Chem. 1996, 61, 2699.
15. Ma, S.; Lu, X.; Li, Z. J. Org. Chem. 1992, 57, 709.
16. Kropp, P. J.; Crawford, S. D. J. Org. Chem. 1994, 59, 3102.
17. Negishi, E.; Van Horn, D. E.; Yoshida, T. J. Am. Chem. Soc.
1985, 107, 6639.
18. (a) Larock, R. C.; Varaprath, S.; Lau, H. H.; Fellows, C. A.
J. Am. Chem. Soc. 1984, 106, 5274. (b) Brown, H. C.; Blue,
C. D.; Nelson, D. J.; Bhat, N. G. J. Org. Chem. 1989, 54, 6064.
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