Palladium-catalyzed silastannation of secondary propargylic alcohols and their derivatives

Article abstract of DOI:10.1055/s-2004-822380

A series of terminal propargylic alcohols and their derivatives were subjected to Pd-catalyzed silastannation. In all reactions, complete regio- and stereoselectivities were observed with the tributyltin moiety exclusively adding to the internal carbon of the triple bond in a cis fashion, including the first example of a diyne bis-silastannation. Silastannation reaction products could sequentially be protiodesilylated or iododestannylated, thus providing synthetic routes to 1,1-gem-disubstituted alkenylstannanes and iodides, respectively.

Full text of DOI:10.1055/s-2004-822380

PAPER
1381
Palladium-Catalyzed Silastannation of Secondary Propargylic Alcohols and
their Derivatives
P
d-Catalyze
d
S
h
ilastannation
o
of Propargy
m
lic
A
lcohols as E. Nielsen, Sebastian Le Quement, David Tanner*
Department of Chemistry, Technical University of Denmark, Kemitorvet, Building 201, 2800 Kgs. Lyngby, Denmark
Fax +45(45)933968; E-mail: dt@kemi.dtu.dk
Received 12 December 2003
Dedicated to Prof. T. Mukaiyama on the occasion of his 77th birthday
cepted catalytic cycle (Scheme 1). The catalytic cycle is
Abstract: A series of terminal propargylic alcohols and their deriv-
atives were subjected to Pd-catalyzed silastannation. In all reac-
tions, complete regio- and stereoselectivities were observed with
the tributyltin moiety exclusively adding to the internal carbon of
believed to involve the following steps: (a) oxidative ad-
dition of R3SiSnR3 to a coordinately unsaturated Pd spe-
cies; (b) coordination of the alkyne; (c) insertion of the
the triple bond in a cis fashion, including the first example of a diyne alkyne into the Pd–Sn bond; and (d) reductive elimination
bis-silastannation. Silastannation reaction products could sequen-
to afford the silastannated product and complete the cata-
tially be protiodesilylated or iododestannylated, thus providing syn-
lytic cycle.
thetic routes to 1,1-gem-disubstituted alkenylstannanes and iodides,
respectively.
R
H
2 L
R3Si
SnR3
Key words: palladium, catalysis, propargylic alcohols, silastanna-
tion, iododestannylation, Stille reaction
Pd
L
L
L
(a)
(d)
(b)
R3SiSnR3
L
R3Si
H
R
Metal-catalyzed element–element addition to alkynes rep-
resents a unique route to bis-functionalized alkenes.1 Sev-
eral combinations of elements, such as B–B, Si–Si, Sn–
Sn, Ge–Ge, B–Si, Sn–B, Ge–Sn, and Si–Sn, may be added
to the triple bond via metal-catalysis, where the Group 10
metals Pd, Ni, and Pt, typically in combination with a
phosphine ligand, have been primary choices of catalysts.
The reaction products are valuable intermediates in the
synthesis of tri- and tetrasubstituted alkenes, e.g. via sub-
sequent metal-catalyzed cross-coupling reactions,2 such
as the Stille,3 or Suzuki reactions.4
PdL4
Pd
R3Sn
(c)
H
H
R
SiR3
R
SiR3
L
L
SnR3
Pd
L
2 L
R3Sn
Scheme 1 Catalytic cycle of the Pd-catalyzed silastannation of ter-
minal alkynes.
Bearing in mind the synthetic potential of vinyl silanes,13
and vinyl stannanes,14 surprisingly few research groups
have utilized the Pd-catalyzed silastannation for synthetic
purposes. Reported applications of the reaction products
comprise precursors of vinyllithium species via Li–Sn
transmetalation, followed by reaction with electro-
philes,7,15 Lewis-acid mediated acylation, replacing the
Si, or Sn moieties,15 Stille reactions with benzyl, allyl, ar-
yl, vinyl, and acyl halides,7,9,16 halodestannylation,7,9,15
halodealkylation at tin,7 and formation of 1-silacyclopen-
tadienes,17 allenes,7 and acyl silanes.9 In their original re-
ports, Chenard reported the failure of propargylic
substrates in Pd-catalyzed silastannation reactions,15
whereas Mitchell has demonstrated moderately successful
silastannation of some 1-methylpropargylic alcohols.7
The Pd-catalyzed silastannation of alkynes was first re-
ported by the groups of Mitchell,5 and Chenard.6 When
performed on terminal alkynes, the reaction proceeds in a
syn-fashion with excellent regio- and stereoselectivity, at-
taching the trialkyltin moiety to the internal carbon of the
triple bond. For nonterminal alkynes, the picture is more
complicated, as mixtures of regioisomers are generally
formed.7,8 Exceptions, however, have been observed in
the case of alkoxyalkynes, where the Si moiety may add
to the a-position of the alkoxy group using Ito’s catalyst
[Pd(OAc)2/tert-alkyl isocyanide],9or to the b-position via
Pd(Ph3P)4 catalysis.10 In Pd(Ph3P)4-catalyzed silastanna-
tion of N-substituted aminoalkynes, the Si moiety adds to
the a-position of the amino group with complete regiose-
lectivity.11
In connection with a research program dealing with the to-
tal synthesis of certain natural products, we have had oc-
casion to reinvestigate the silastannation of propargylic
alcohols, and we now wish to report the extension of the
reaction scope to a broader selection of these substrates,
and their derivatives, including the first bis-silastannation
of a diyne. In addition, applications of the reaction prod-
ucts for the synthesis of 1,1-gem-disubstituted alkenyl-
Concerning the reaction mechanism, Ito and Nakatsuji
have performed a theoretical study, including the issue of
regioselectivity,12 which gives support to the generally ac-
SYNTHESIS 2004, No. 9, pp 1381–1390
Advanced online publication: 18.05.2004
x
x
.
x
x
.2
0
0
4
DOI: 10.1055/s-2004-822380; Art ID: C11903SS
© Georg Thieme Verlag Stuttgart · New York

1382
T. E. Nielsen et al.
PAPER
stannanes and iodides, and as coupling partners in Stille
reactions, are also described.
Table 1 Pd-Catalyzed Silastannation of Propargylic Alcohols
Following a modified procedure of Midland,18 the termi-
nal propargylic alcohols 1d–i were readily obtained by
treating the parent aldehydes with lithium acetylide. Like-
wise, diyne 1j was obtained by treating ethyl benzoate
with a further equivalent of lithium acetylide. As illustrat-
ed for 1-phenylpropyn-1-ol (1d), further derivatizations
were accomplished via standard protective group methods
to give substrates 2a–f (Scheme 2).
Entry Alkyne
1
Product
Yield (%)a
83
95
85
85
SiMe3
SnBu3
HO
( )3
HO
( )3
1a
3a
2
SiMe3
SnBu3
HO
( )2
Ph
Ph
2b
2c
HO
( )2
O
OTBDMS
Ph
1b
(b)
(c)
3b
3
SiMe3
SnBu3
HO
(d)
(a)
Ph
HO
Ph
2a
1c
2d
OH
OAc
OMe
Ph
3c
(e)
(f)
1d
4
5
OH
OH
SnBu3
SiMe3
Ph
Ph
Ph
O
2f
2e
1d
OMEM
Br
3d
80
72
67
74
72
71
OH
OH
SnBu3
SiMe3
t-Bu
t-Bu
Scheme 2 Reagents and conditions: (a) Ac2O, 4-DMAP, Et3N,
CH2Cl2, r.t., 85%; (b) TBDMSCl, imidazole, DMF, r.t., 92%; (c)
NaH, CH2=CHCH2Br, KI, THF, r.t., 59%; (d) NaH, MeI, THF, r.t.,
56%; (e) NaH, 2-Br-C6H4CH2Br, TBAI, THF, r.t., 72%; (f) MEMCl,
DIPEA, CH2Cl2, 0 °C, 80%.
1e
3e
6
OH
OH
SnBu3
SiMe3
Cy
Cy
In a first round of silastannation experiments, a series of
unprotected propargylic alcohols 1c–j, together with ter-
minal alkynes 1a,b were tested. Initial studies on the
choice of catalyst revealed that Pd2(dba)3·CHCl3, in com-
bination with 1–2 equivalents of Ph3P per Pd, generally
gave the most satisfying results, when compared to
Pd(Ph3P)4 and other standard catalysts. As illustrated in
Table 1, good to excellent yields were obtained, with the
expected regio- and stereoselectivity. All silastannations
listed in Table 1 were carried out with catalyst loadings
corresponding to 5% Pd.19 Notably, the sterically congest-
ed diyne 1j was efficiently silastannated (entry 10), there-
by providing the first example of a bis-silastannation
(none of the mono-silastannated product was observed).
1f
3f
7
OH
OH
SnBu3
SiMe3
Ph
Ph
1g
3g
8
OH
OH
( )4
SnBu3
( )4
SiMe3
1h
3h
9
OH
OH
SnBu3
SiMe3
1-Np
1-Np
In general, the stereochemistry of the silastannation prod-
ucts 3a–j, 4b–d, and 4f–h was assigned by inspection of
the coupling constants from Sn to the vinyl proton, e.g.
J(119Sn,H) was found to be in the range of 165–182 Hz,
which is strongly evident of a trans-relationship between
Sn and the vinyl proton.
1i
3i
10b
SiMe3
HO
Ph
SnBu3
SnBu3
HO
Ph
1j
These promising results encouraged us to examine the im-
portance of the O-protecting group. For this purpose, pro-
pargylic alcohol derivatives 2a–h were subjected to the
silastannation protocol (Table 2).
SiMe3
3j
a Isolated yield after flash column chromatography.
b 2.10 equiv of Bu3SnSiMe3 were employed.
Synthesis 2004, No. 9, 1381–1390 © Thieme Stuttgart · New York

PAPER
Pd-Catalyzed Silastannation of Propargylic Alcohols
1383
Table 2 Pd-Catalyzed Silastannation of O-Protected Propargylic
Alcohols
Although the propargylic acetate 2a fails to produce any
of the desired product 4a under the reaction conditions
(entry 1),15 the silastannation products were formed in
good to excellent yields when other common protecting
groups, such as TBDMS, allyl, bromobenzyl, and MEM,
were employed (entries 2–4, 6–8). Notably, the methyl
ethers 2d and 2g were found to give the corresponding si-
lastannation products 4d and 4g in near quantitative yields
(entries 4 and 7). It is also noteworthy that, whereas the si-
lastannation of the 1-phenyl derivative 2e fails and results
in decomposition, the silastannation of the less substituted
2h was effected without any competing side-reactions or
cross-coupling of the aryl bromide (Entry 8).
Entry
1
Alkyne
Product
Yield (%)a
0
2a
OAc
Ph
SnBu3
SiMe3
4a
In Pd-catalyzed hydrostannation of terminal propargylic
alcohol derivatives,20 the steric bulk of the substrate and
the nature of the phosphine ligand are highly important for
the reaction regioselectivity, where main products nor-
mally are the trans-disubstituted alkenylstannanes result-
ing from the overall cis-addition of Bu3SnH, attaching the
Sn moiety with high b-selectivity to the triple bond.21 Al-
though some efforts have been aimed at higher a-selectiv-
ities, e.g. via Mo-catalysis,22 the direct access to 1,1-gem-
disubstituted alkenylstannanes from propargylic alcohol
derivatives is difficult. Pleasingly, selected O-protected
silastannation products 4f and 4g were smoothly desilylat-
ed using the conditions of Ritter,23 to provide the 1,1-gem-
disubstituted alkenylstannanes in high yields (Table 3).
Unexpectedly, total decomposition was observed when
attempts were made to desilylate the unprotected deriva-
tive 3d.
2
3
2b
2c
85
61
OTBDMS
SnBu3
Ph
SiMe3
4b
O
SnBu3
SiMe3
Ph
4c
4
5
2d
2e
>95
OMe
SnBu3
SiMe3
Ph
4d
0
Br
O
SnBu3
SiMe3
Table 3 Desilylation of Silastannation Products
Ph
4e
6
2f
88
>95
78
OMEM
SnBu3
Ph
Entry Substrate
Product
Yield (%)a
0
SiMe3
4f
1
2
3
3d
7b
OH
Ph
OMe
OMe
SnBu3
SnBu3
SiMe3
1-Np
1-Np
2g
5
4f
85
89
OMEM
SnBu3
4g
8c
Br
Ph
O
6
Br
O
SnBu3
SiMe3
4g
OMe
SnBu3
1-Np
4h
2h
7
a Isolated yield after flash column chromatography.
a Isolated yield after flash column chromatography.
b Substrate 2g was made from the corresponding alcohol 1i via the
NaH/MeI protocol (72%; see the experimental section for details).
c Substrate 2h was made from the corresponding alcohol 1c via the
NaH/2-BrC6H4CH2Br/TBAI protocol (79%; see the experimental sec-
tion for details).
When treated with a suitable source of electrophilic halo-
gen, vinyl stannanes may be converted to vinyl halides un-
der mild reaction conditions. By simple treatment with
iodine, the alkenylstannanes 6 and 7 were cleanly convert-
Synthesis 2004, No. 9, 1381–1390 © Thieme Stuttgart · New York

1384
T. E. Nielsen et al.
PAPER
ed into the corresponding 1,1-gem-disubstituted alkenyl TBDMS, and 2-bromobenzyl ethers. The reaction condi-
iodides, 8 and 9, respectively, thereby establishing a con- tions also apply for a diyne to give the corresponding bis-
venient regio- and stereoselective overall route to this silastannated product. The reaction products are valuable
compound class from terminal alkynes (Scheme 3).
precursors for 1,1-gem-disubstituted alkenylstannanes,
and iodides, which may be obtained by sequential treat-
ment with TBAF, and iodine. Problems with traditionally
sluggish Stille reactions of sterically hindered silastanna-
tion products, and 1,1-gem-disubstituted alkenylstan-
nanes in general, appear to be easily overcome using
Corey’s CuCl/LiCl-mediated Stille coupling protocol.
Thus, the combination of regioselective silastannation
with efficient cross-coupling reactions provides entry to
useful building blocks for further synthetic use.
OMEM
OMEM
(a)
I
SnBu3
Ph
Ph
8
6
OMe
(a)
OMe
SnBu3
I
1-Np
1-Np
7
9
Scheme 3 Reagents and conditions: (a) I2, CH2Cl2, 0 °C. Yields:
88% (8); 95% (9).
1H (300 MHz) and 13C (75 MHz) NMR spectra were recorded using
CDCl3 as the solvent, and signal positions (d values) were measured
relative to the signals for CHCl3 (7.27) and CDCl3 (77.0), respec-
tively. Tin–hydrogen coupling constants, J(Sn,H), are given as the
117Sn and 119Sn values, or average values. IR spectra were obtained
for thin films on AgCl plates, and only the strongest/structurally
most important peaks are listed. Microanalyses were performed by
the Microanalysis Laboratory, Department of Physical Chemistry,
University of Vienna, Austria, and at the Department of Chemistry,
University of Bath, England. HRMS was performed at the Depart-
ment of Chemistry, University of Copenhagen, Denmark, and the
Department of Chemistry, University of Bath, England. Molecular
mass determinations (high-resolution mass spectrometry) for sub-
stances containing Bu3Sn are based on 120Sn and typically made on
the [M – Bu]+, unless otherwise stated. All compounds on which
HRMS were performed exhibited clean 1H NMR spectra and
showed one spot on TLC analysis, using UV light, and a solution of
5–10% phosphomolybdic acid in ethanol for visualization.
Stille couplings of selected stannanes of the present study
were briefly examined. When stannanes 3d and 6 were
subjected to standard coupling procedures with iodoben-
zene, e.g. Pd2(dba)3·CHCl3, in combination with a phos-
phine ligand (a total of 15 phosphine ligands were tested),
in THF (reflux), or DMF (70 °C), with or without catalytic
amounts of Cu(I) sources,24 no general method could be
established to provide the desired coupling products 10
and 11 in good yields. The literature clearly indicates that
the Stille reaction of hindered stannanes with aryl halides
is difficult,3 often affording very low yields and mixtures
of isomeric coupling products. Most likely, this limitation
on the Stille reaction is associated with steric hindrance,
and alternative reaction modes, such as the cine substitu-
tion,25 have been reported to set in. Accordingly, our at-
tention turned to Corey’s improved procedure for Cu-
mediated Stille reactions.26 The procedure relies on the
use of a large excess of CuCl (5 equiv) and LiCl (6 equiv)
in DMSO, providing the coupling products in satisfying
yields (Scheme 4).
Column chromatography was performed using Amicron Matrex sil-
ica gel (35–70 mm). All solvents were distilled prior to use. THF
was distilled under nitrogen from Na-benzophenone. CH2Cl2 and
DMF were dried over calcium hydride and distilled under nitrogen.
DMSO was dried over 4Å MS, and degassed (4×) by the freeze-
pump-thaw process (–78 °C, r.t., argon). CuCl was prepared accord-
ing to Österlöf.27 CuCN and LiCl were oven-dried prior to use and
used without further purification. Commercially available com-
pounds were used as received unless otherwise indicated. All reac-
tions were carried out under dry argon using carefully flame-dried
glassware. Argon gas was dried by passage through P2O5 and silica
gel.
OH
(a)
OH
SnBu3
SiMe3
Ph
Ph
SiMe3
3d
10
Terminal Propargylic Alcohols 1d–j; General Procedure
A 250 mL round-bottomed flask containing THF (100 mL) was
cooled to –78 °C. A balloon filled with approximately 4 L of acety-
lene was attached to the system via a needle. The liquid was stirred
for 1 h in which time the balloon contracted corresponding to the
amount of absorbed acetylene.28 To the resultant solution was added
n-BuLi (1.6 M in hexanes, 37 mL 55 mmol) during 20 min via a sy-
ringe, and the solution was stirred for 10 min. To the reaction mix-
ture was dropwise added a solution of the appropriate aldehyde (50
mmol) in THF (15 mL) at –78 °C. The mixture was stirred for 1 h
at –78 °C, and then allowed to reach r.t. during which time the bal-
loon expanded to accommodate the excess of acetylene, and subse-
quently quenched with H2O (20 mL). To the mixture was added 2–
3 portions of K2CO3 until the aqueous phase looked pasty. The THF
was decanted off and the aqueous phase was extracted with Et2O (2
× 30 mL). The combined organic phases were dried (MgSO4), fil-
tered and rotary evaporated. This gave a thick, orange oil, which
was purified by flash column chromatography on silica gel (hex-
ane–EtOAc, 4:1) to afford the propargylic alcohol.
MEMO
Ph
OMEM
SnBu3
(a)
Ph
6
11
Scheme 4 Reagents and conditions: (a) PhI, Pd2(dba)3·CHCl3 (0.05
equiv, PPh3 (0.2 equiv), CuCl (5 equiv), LiCl (6 equiv), DMSO, 60
°C. Yields: 65% (10); 81% (11).
In summary, a series of terminal propargylic alcohols and
their O-protected derivatives were subjected to
Pd2(dba)3·CHCl3/PPh3-catalyzed silastannation with
Bu3SnSiMe3. A range of protecting groups for the propar-
gylic alcohol were found to be compatible with the reac-
tion, as illustrated by the tolerance of methyl, allyl, MEM,
Synthesis 2004, No. 9, 1381–1390 © Thieme Stuttgart · New York

PAPER
Pd-Catalyzed Silastannation of Propargylic Alcohols
1385
1-Phenylprop-2-yn-1-ol (1d)29
Yield: 81%; thick, clear yellow oil.
1H NMR (300 MHz, CDCl3): d = 7.58–7.49 (m, 2 H), 7.42–7.30 (m,
3 H), 6.45 (d, J = 2 Hz, 1 H), 2.64 (d, J = 2 Hz, 1 H), 2.12 (s, 3 H).
1H NMR (300 MHz, CDCl3): d = 7.55–7.25 (m, 5 H), 5.38 (d, J = 2
Hz, 1 H), 2.62 (d, J = 2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 169.6, 136.5, 129.0, 128.7, 127.6,
75.3, 65.3, 21.0.
13C NMR (75 MHz, CDCl3): d = 140.2, 128.7, 128.5, 126.8, 83.8,
(1-tert-Butyldimethylsilyloxyprop-2-ynyl)benzene (2b)38
The alcohol 1d (1.06 g, 8.0 mmol), tert-butyldimethylsilyl chloride
(1.45 g, 9.6 mmol), and imidazole (2.45 g, 36.0 mmol) was dis-
solved in DMF (10 mL) and stirred overnight. H2O (10 mL) and
pentane (50 mL) were added, and the organic phase was separated.
The aqueous phase was extracted with portions of pentane (2 × 25
mL). The combined organics were washed with H2O (5 × 10 mL),
and brine (5 mL), dried (MgSO4), filtered and rotary evaporated.
The residue was purified by flash column chromatography on silica
gel (hexane–EtOAc, 20:1) to give the crude title compound 2b (1.81
g, 92%) as a colorless oil.
75.0, 64.2.
4,4-Dimethylpent-1-yn-3-ol (1e)30
Yield: 68%, clear yellow oil.
1H NMR (300 MHz, CDCl3): d = 4.04 (d, J = 2 Hz, 1 H), 2.48 (d,
J = 2 Hz, 1 H), 1.03 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 83.6, 73.6, 70.9, 35.4, 25.0.
1-Cyclohexylprop-2-yn-1-ol (1f)31
Yield: 70%; clear colorless oil.
1H NMR (300 MHz, CDCl3): d = 7.46–7.39 (m, 2 H), 7.32–7.17 (m,
3 H), 5.41 (d, J = 2 Hz, 1 H), 2.48 (d, J = 2 Hz, 1 H), 0.87 (s, 9 H),
0.11 (s, 3 H), 0.07 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 141.1, 128.1, 127.6, 125.8, 84.6,
73.4, 64.4, 25.6, 18.1, –4.7, –5.1.
1H NMR (300 MHz, CDCl3): d = 4.23–4.10 (m, 1 H), 2.48 (d, J = 2
Hz, 1 H), 1.85–0.90 (m, 11 H).
13C NMR (75 MHz, CDCl3): d = 83.9, 73.6, 67.0, 43.9, 28.3, 27.9,
26.4, 25.8 (two signals).
1-Phenylpent-1-en-4-yn-3-ol (1g)32
Yield: 81%; yellow oil.
(1-Allyloxyprop-2-ynyl)benzene (2c)
A solution of the alcohol 1d (132 mg, 1.0 mmol) in THF (2 mL) was
added dropwise to a suspension of NaH (24 mg, 1.0 mmol) in THF
(2 mL). A crystal of KI was added, before the dropwise addition of
allyl bromide (182 mg, 1.5 mmol). The mixture was stirred until
TLC indicated a complete conversion, and H2O (2 mL) and Et2O
(30 mL) were added to the reaction mixture. The organic phase was
isolated, and the aqueous phase was extracted with Et2O (2 × 20
mL). The combined organic phases were washed with brine (2 × 5
mL), dried (MgSO4), filtered and rotary evaporated. The residue
was purified by flash column chromatography on silica gel (hex-
ane–EtOAc, 20:1) to give the title compound 2c (102 mg, 59%) as
a colorless oil.
1H NMR (300 MHz, CDCl3): d = 7.55–7.15 (m, 5 H), 6.80 (dd,
J = 16, 2 Hz, 1 H), 6.30 (dd, J = 16, 6 Hz, 1 H), 5.06 (m, 1 H), 2.63
(d, J = 2 Hz, 1 H), 2.02 (br s, 1 H).
13C NMR (75 MHz, CDCl3): d = 135.9, 132.4, 128.7, 128.3, 127.5,
126.9, 82.8, 74.7, 62.8.
Oct-1-yn-3-ol (1h)33
Yield: 70%; clear yellow oil.
1H NMR (300 MHz, CDCl3): d = 4.35–4.15 (m, 1 H), 2.33 (d, J = 2
Hz, 1 H), 1.85–0.75 (m, 11 H).
13C NMR (75 MHz, CDCl3): d = 84.6, 72.3, 61.3, 37.0, 29.9, 24.1,
22.0, 13.3.
IR (neat): 3032, 2860, 1647, 1452, 1060, 1009, 926, 759, 742, 699
cm–1.
1-Naphthylprop-2-yn-1-ol (1i)34
1H NMR (300 MHz, CDCl3): d = 7.56–7.49 (m, 2 H), 7.43–7.31 (m,
3 H), 6.04–5.90 (m, 1 H), 5.35 (ddd, J = 17, 3, 2 Hz, 1 H), 5.24 (ddd,
J = 10, 3, 2 Hz, 1 H), 5.22 (d, J = 2 Hz, 1 H), 4.22 (dddd,
J = 12, 5, 2, 1 Hz, 1 H), 4.13 (dddd, J = 13, 6, 2, 1 Hz, 1 H), 2.65 (d,
J = 2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 138.1, 134.1, 128.5, 128.4, 127.3,
117.7, 81.6, 75.5, 70.3, 69.1.
Yield: 70%; fluffy, white solid; mp 61–62 °C (Lit.35 mp 61–63 °C).
1H NMR (300 MHz, CDCl3): d = 8.29 (m, J = 8 Hz, 1 H), 7.92–7.83
(m, 3 H), 7.62–7.45 (m, 3 H), 6.14 (s, 1 H), 2.35 (br s, 1 H).
13C NMR (75 MHz, CDCl3): d = 135.0, 133.9, 130.3, 129.3, 128.6,
126.4, 125.8, 125.1, 124.5, 123.7, 83.2, 75.4, 62.5.
3-Phenylpenta-1,4-diyn-3-ol (1j)36
Yield: 74%; thick, clear yellow oil.
Anal. Calcd for C12H12O: C, 83.67; H, 7.04. Found: C, 83.39; H,
6.83.
1H NMR (300 MHz, CDCl3): d = 7.78–7.63 (m, 2 H), 7.37–7.10 (m,
3 H), 2.88 (br s, 1 H), 2.69 (s, 2 H)
(1-Methoxyprop-2-ynyl)benzene (2d)39
To a suspension of NaH (182 mg, 7.6 mmol) in THF (5 mL) at r.t.
was added dropwise a solution of propargyl alcohol 1d (1.00 g, 7.6
mmol) in THF (5 mL). The reaction mixture was stirred for 10 min,
before the dropwise addition of MeI (1.61 g, 11.4 mmol) dissolved
in THF (5 mL). The mixture was left stirring overnight, then diluted
with H2O (5 mL), and extracted with portions of CH2Cl2 (4 × 50
mL). The combined organic extracts were washed with brine (2 × 5
mL), then dried, filtered and concentrated by rotary evaporation.
The residue was purified by flash column chromatography on silica
gel (hexane–EtOAc, 5:1) to give the title compound 2d (624 mg,
56%) as a colorless oil (turning brown, if not stored in the dark).
1H NMR (300 MHz, CDCl3): d = 7.62–7.29 (m, 5 H), 5.10 (d, J = 2
Hz, 1 H), 3.46 (3 H, s), 2.66 (d, J = 2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 138.0, 128.5, 128.3, 127.3, 81.3,
75.7, 72.8, 55.9.
13C NMR (75 MHz, CDCl3): d = 140.7, 128.9, 128.4, 125.7, 83.3,
73.7, 64.6.
Acetic Acid 1-Phenylprop-2-ynyl Ester (2a)37
The alcohol 1d (524 mg, 4.0 mmol) was dissolved in CH2Cl2 (7
mL). To the mixture was added 4-dimethylaminopyridine (244 mg,
2.0 mmol) in one portion, followed by Et3N (567 mg, 5.6 mmol),
and Ac2O (490 mg, 4.8 mmol). After stirring for 2 h at r.t., TLC in-
dicated the complete conversion of the substrate. The reaction mix-
ture was poured into a separating funnel containing H2O (15 mL)
and CH2Cl2 (8 mL). The organic phase was isolated, and the aque-
ous phase was extracted with CH2Cl2 (2 × 8 mL). The combined or-
ganic layers were washed with brine (3 × 5 mL), dried (MgSO4),
filtered and rotary evaporated. The residue was purified by flash
column chromatography on silica gel (hexane–EtOAc, 10:1) to give
the crude title compound 2a (590 mg, 85%) as a colorless oil.
Synthesis 2004, No. 9, 1381–1390 © Thieme Stuttgart · New York

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T. E. Nielsen et al.
PAPER
1-Bromo-2-(1-phenylprop-2-ynyloxymethyl)benzene (2e)
To a suspension of NaH (120 mg, 5 mmol) in THF (5 mL) at r.t. was
added dropwise a solution of propargyl alcohol 1d (280 mg, 5
mmol) in THF (5 mL). The reaction mixture was stirred for 10 min,
before the addition of a crystal of Bu4NI, followed by dropwise ad-
dition of 2-bromobenzyl bromide (1.00 g, 4 mmol) dissolved in
THF (5 mL). The mixture was left stirring overnight, then diluted
with H2O (5 mL), and extracted with portions of CH2Cl2 (4 × 50
mL). The combined organic extracts were washed with brine (10
mL), then dried, filtered and concentrated by rotary evaporation.
The residue was purified by flash column chromatography on silica
gel (hexane–EtOAc, 30:1) to give the title compound 2e (867 mg,
72%) as a colorless oil.
after flash column chromatography on silica gel (hexane–EtOAc,
30:1) the title compound 2h (1.99 g, 79%) as a colorless oil.
1H NMR (300 MHz, CDCl3): d = 7.52–7.32 (m, 2 H), 7.32–6.99 (m,
2 H), 4.61 (s, 2 H), 4.11 (d, J = 2 Hz, 1 H), 2.42 (d, J = 2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 136.7, 132.4, 129.2, 129.0, 127.2,
122.8, 79.4, 74.8, 70.9, 57.7.
Silastannation of Terminal Propargylic Alcohols and their De-
rivatives; General Procedure
A solution of Ph3P (48 mg, 0.18 mmol), tris(dibenzylideneace-
tone)dipalladium(0)-CHCl3 complex (45 mg, 0.043 mmol) was
stirred for 10 min in THF (10 mL). To the mixture was added tri-
methyl(tributylstannyl)silane (3.81 g, 10.5 mmol) and the propar-
gylic alcohol (10 mmol) in THF (5 mL). The resulting solution was
refluxed overnight. The dark brown reaction mixture was cooled to
r.t. and diluted with Et2O (100 mL), filtered through a pad of Celite,
and concentrated by rotary evaporation. The residue was purified by
flash column chromatography on silica gel (hexane–EtOAc, 1:0–
10:1) to afford the silastannane.
IR (neat): 1717, 1599, 1495, 1240, 1095, 754, 692 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.62–7.24 (m, 8 H), 7.19–7.11 (m,
1 H), 5.31 (d, J = 2 Hz, 1 H), 4.82 (d, J = 13 Hz, 1 H), 4.72 (d, J = 13
Hz, 1 H), 2.71 (d, J = 2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 137.7, 136.9, 132.4, 129.6, 129.0,
128.5, 128.4, 127.3 (two peaks), 122.9, 81.1, 76.2, 71.0, 69.6.
Anal. Calcd for C16H13BrO: C, 63.81; H, 4.35. Found: C, 63.60; H,
4.22.
(Z)-4-Tributylstannyl-5-trimethylsilylpent-4-en-1-ol (3a)
Yield: 83%; colorless oil.
IR (neat): 3318, 2956, 1458, 1376, 1247, 1071, 837, 688 cm–1.
[1-(2-Methoxyethoxymethoxy)prop-2-ynyl]benzene (2f)
The propargyl alcohol 1d (1.32 g, 10.0 mmol) was dissolved in
CH2Cl2 (20 mL). The solution was cooled to 0 °C, before the addi-
tion of methoxyethoxymethyl chloride (1.87 g, 15 mmol), followed
by dropwise addition of i-Pr2EtN (1.94 g, 15 mmol). The reaction
mixture was stirred overnight at r.t., and then poured into a separat-
ing funnel containing H2O (5 mL). The organic phase was separat-
ed, and the aqueous phase was extracted with CH2Cl2 (2 × 10 mL).
The combined organic phases were washed with brine (5 mL), dried
(MgSO4), filtered, and rotary evaporated. The residue was purified
by flash column chromatography on silica gel (hexane–EtOAc, 5:1)
to give the title compound 2f (1.76 g, 80%) as a colorless oil.
1H NMR (300 MHz, CDCl3): d = 6.40 [t, J = 2 Hz, J(119Sn,H) = 179
Hz, J(117Sn,H) = 172 Hz, 1 H], 3.64 (t, J = 7 Hz, 2 H), 2.36 [dt,
J = 2, 8 Hz, J(Sn,H) = 43 Hz, 2 H], 1.68–1.24 (m, 14 H), 1.01–0.83
(m, 15 H), 0.11 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 164.9, 144.1, 62.5, 43.6, 32.8, 29.4,
27.5, 13.6, 11.3, 0.2.
Anal. Calcd for C20H44OSiSn: C, 53.70; H, 9.91. Found: C, 53.84;
H, 10.20.
(Z)-3-Tributylstannyl-4-trimethylsilylbut-3-en-1-ol (3b)
Yield: 95%; colorless oil.
IR (neat): 3348, 2956, 1461, 1247, 1044, 843 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.47 [s, J(119Sn,H) = 173 Hz,
J(117Sn,H) = 166 Hz, 1 H], 3.57 (q, J = 6 Hz, 2 H), 2.56 [t, J = 6 Hz,
J(Sn,H) = 44 Hz, 2 H], 1.58–1.21 (m, 13 H), 1.06–0.80 (m, 15 H),
0.11 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 161.3, 148.4, 60.8, 50.0, 29.1, 27.4,
13.4, 11.2, 0.1.
IR (neat): 3290, 1654, 1456, 1108, 1034, 908, 850, 750, 700 cm–1.
1H NMR (CDCl3, 300 MHz): d = 7.55–7.50 (m, 2 H), 7.42–7.30 (m,
3 H), 5.46 (d, J = 2 Hz, 1 H), 5.09 (d, J = 7 Hz, 1 H), 4.77 (d, J = 7
Hz, 1 H), 3.84–3.68 (m, 2 H), 3.60–3.54 (m, 2 H), 3.40 (s, 3 H), 2.60
(d, J = 2 Hz, 1 H).
13C NMR (CDCl3, 75 MHz): d = 138.3, 128.6, 127.5, 92.9, 81.5,
75.3, 71.7, 67.4, 67.2, 59.0.
Anal. Calcd for C13H16O3: C, 70.89; H, 7.32. Found: C, 70.88; H,
7.20.
HRMS (FAB): m/z calcd for C15H33OSiSn [M – C4H9]+: 377.1323;
found: 377.1335.
1-(1-Methoxyprop-2-ynyl)naphthalene (2g)
Anal. Calcd for C19H42OSiSn: C, 52.66; H, 9.77. Found: C, 52.93;
H, 9.88.
Following the procedure for the synthesis of 2d, the reaction of NaH
(182 mg, 7.6 mmol), propargyl alcohol 1i (1.39 g, 7.6 mmol), and
MeI (1.61 g, 11.4 mmol) gave, after flash column chromatography
on silica gel (hexane–EtOAc, 10:1), the title compound 2g (1.08 g,
72%) as a yellow oil (turning gradually darker).
(Z)-2-Tributylstannyl-3-trimethylsilylprop-2-en-1-ol (3c)7
Yield: 85%; colorless oil.
IR (neat): 3319, 2956, 1458, 1376, 1247, 1062, 1021, 839, 690 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.63 [t, J = 2 Hz, J(119Sn,H) = 169
Hz, J(117Sn,H) = 162 Hz, 1 H], 4.25 [dd, J = 2, 6 Hz, J(Sn,H) = 26
Hz, 2 H], 1.65–1.25 (m, 12 H), 1.12–0.87 (m, 15 H), 0.14 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 163.6, 140.5, 128.3, 73.6, 29.2,
27.4, 13.7, 11.0, 0.11.
IR (neat): 3050, 2935, 1598, 1510, 1462, 1300, 1188, 1165, 1071,
974, 802, 781, 650 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.28–8.20 (m, 1 H), 7.92–7.78 (m,
3 H), 7.62–7.40 (m, 3 H), 5.72 (d, J = 2 Hz, 1 H), 3.43 (s, 3 H), 2.71
(d, J = 2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 134.0, 133.1, 130.8, 129.5, 128.6,
126.3, 125.8, 125.0, 124.0, 81.1, 76.4, 71.3, 55.8.
Anal. Calcd for C18H40OSiSn: C, 51.56; H, 9.62. Found: C, 51.44;
H, 9.66.
No satisfactory elemental analysis could be obtained.
(Z)-1-Phenyl-2-tributylstannyl-3-trimethylsilylprop-2-en-1-ol
(3d)
1-Bromo-2-prop-2-ynyloxymethylbenzene (2h)40
Following the procedure for the synthesis of 2e, the reaction of pro-
pargyl alcohol 1c (840 mg, 15 mmol), NaH (360 mg, 15), 2-bro-
mobenzyl bromide (2.68 g, 11.2 mmol), and a crystal of Bu4NI gave
Yield: 85%; thick, slightly yellow oil.
Synthesis 2004, No. 9, 1381–1390 © Thieme Stuttgart · New York

PAPER
Pd-Catalyzed Silastannation of Propargylic Alcohols
1387
IR (neat): 3423, 2920, 1460, 1247, 1053, 960, 862, 836, 742, 699
cm–1.
Anal. Calcd for C23H50OSiSn: C, 56.55; H, 10.13. Found: C, 56.85;
H, 9.87.
1H NMR (300 MHz, CDCl3): d = 7.31–7.17 (m, 5 H), 6.66 [d, J = 2
Hz, J(119Sn,H) = 167 Hz, J(117Sn,H) = 159 Hz, 1 H], 5.20 [dd,
J = 2, 4 Hz, J(Sn,H) = 37 Hz, 1 H], 1.91 (d, J = 4 Hz, 1 H), 1.37–
1.04 (m, 12 H), 0.85–0.66 (m, 15 H), 0.13 (s, 9 H).
HRMS (FAB): m/z calcd for C19H39SiSn [M – C4H9 – H2O]+:
415.1851; found: 415.1851.
(Z)-1-(1-Naphthyl)-2-tributylstannyl-3-trimethylsilylprop-2-
en-1-ol (3i)
Yield: 72%; colorless oil.
IR (neat): 3364, 2955, 1458, 1246, 1048, 864, 780 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.25–8.19 (m, 1 H), 7.89–7.76 (m,
3 H), 7.57–7.39 (m, 3 H), 6.85 [d, J = 2 Hz, J(119Sn,H) = 171 Hz,
J(117Sn,H) = 163 Hz, 1 H], 6.07 [dd, J = 2, 6 Hz, J(Sn,H) = 23 Hz,
1 H], 1.97 (d, J = 6 Hz, 1 H), 1.41–1.08 (m, 12 H), 0.96–0.68 (m, 15
H), 0.18 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 166.4, 142.2, 141.9, 128.2, 127.4,
127.1, 83.8, 29.0, 27.4, 13.6, 11.6, 0.3.
Anal. Calcd for C24H44OSiSn: C, 58.19; H, 8.95. Found: C, 58.38;
H, 8.73.
(Z)-4,4-Dimethyl-2-tributylstannyl-1-trimethylsilylpent-1-en-3-
ol (3e)
Yield: 80%; colorless oil.
IR (neat): 3482, 2954, 1464, 1376, 1361, 1248, 1070, 1003, 860,
758, 690 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.55 [d, J = 1 Hz, J(119Sn,H) = 180
Hz, J(117Sn,H) = 173 Hz, 1 H], 3.91 [dd, J = 1, 2 Hz, J(Sn,H) = 42
Hz), 1 H], 1.61–1.25 (m, 12 H), 1.03–0.86 (m, 15 H), 0.89 (s, 9 H),
0.15 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 165.3, 140.7, 137.9, 134.1, 131.8,
128.7, 128.6, 126.1, 125.6, 125.6, 125.0, 124.2, 77.8, 29.1, 27.4,
13.6, 11.6, 0.3.
Anal. Calcd for C28H46OSiSn: C, 61.65; H, 8.50. Found: C, 61.57;
H, 8.83.
(Z,Z)-3-Phenyl-2,4-bis(tributylstannyl)-1,5-bis(trimethylsi-
lyl)penta-1,4-dien-3-ol (3j)
Yield: 71%; colorless oil.
IR (neat): 2954, 1464, 1376, 1247, 1072, 1004, 860, 701 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.32–7.12 (m, 5 H), 5.95 [s,
J(119Sn,H) = 182 Hz, J(117Sn,H) = 174 Hz, 2 H], 2.46 (s, 1 H), 1.55–
1.23 (m, 12 H), 0.98–0.72 (m, 15 H), 0.11 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 167.0, 144.6, 128.3, 88.3, 35.9,
29.3, 27.6, 26.5, 13.7, 12.8, 0.4.
Anal. Calcd for C22H48OSiSn: C, 55.58; H, 10.18. Found: C, 55.90;
H, 10.15.
(Z)-1-Cyclohexyl-2-tributylstannyl-3-trimethylsilylprop-2-en-
1-ol (3f)
Yield: 72%; colorless oil.
IR (neat): 2955, 2924, 1451, 1247, 1072, 1012, 862, 836 cm–1.
13C NMR (75 MHz, CDCl3): d = 173.2, 144.8, 143.9, 127.7, 127.6,
126.7, 92.6, 29.3, 27.6, 13.7, 13.3, 0.5.
1H NMR (300 MHz, CDCl3): d = 6.40 [d, J = 1 Hz, J(119Sn,H) = 176
Hz, J(117Sn,H) = 168 Hz, 1 H], 3.76 [d, J = 7 Hz, J(Sn,H) = 47 Hz),
1 H], 1.90–0.78 (m, 38 H), 0.12 (s, 9 H).
Anal. Calcd for C41H80OSi2Sn2: C, 55.79; H, 9.14. Found: C, 56.01;
H, 9.25.
(Z)-[1-(tert-Butyldimethylsilyloxy)-2-tributylstannyl-3-trimeth-
ylsilylallyl]benzene (4b)
Yield: 85%; colorless oil.
IR (neat): 2955, 2928, 1464, 1248, 1089, 1064, 884, 836, 777 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.35–7.25 (m, 5 H), 6.64 [d, J = 1
Hz, J(119Sn,H) = 165 Hz, J(117Sn,H) = 158 Hz, 1 H], 5.16 [s,
J(Sn,H) = 55 Hz, 1 H], 1.38–1.10 (m, 12 H), 1.05–0.68 (m, 15 H),
0.96 (s, 9 H), 0.19 (s, 9 H), 0.09 (s, 3 H), 0.08 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 167.7, 142.0, 88.0, 42.0, 30.5, 29.3,
27.5, 27.4, 26.5, 26.4, 26.2, 13.7, 11.9, 0.3.
Anal. Calcd for C24H50OSiSn: C, 57.48; H, 10.05. Found: C, 58.17;
H, 10.11.
(Z)-5-Phenyl-2-tributylstannyl-1-trimethylsilylpenta-1,4-dien-
3-ol (3g)
Yield: 67%; colorless oil.
IR (neat): 3427, 2954, 1603, 1460, 1376, 1247, 967, 859, 750, 692
cm–1.
13C NMR (75 MHz, CDCl3): d = 167.4, 143.2, 143.0, 127.8, 126.6,
126.5, 87.5, 29.1, 27.5, 26.2, 18.6, 13.6, 11.9, 0.2, –3.9, –4.7.
1H NMR (300 MHz, CDCl3): d = 7.42–7.19 (m, 5 H), 6.65 [d, J = 1
Hz, J(119Sn,H) = 168 Hz, J(117Sn,H) = 161 Hz, 1 H], 6.53 (d, J = 18
Hz, 1 H), 6.17 (d, J = 6 Hz, 1 H), 6.12 (d, J = 6 Hz, 1 H), 4.84–4.78
[m, J(Sn,H) = 40 Hz, 1 H], 1.78 (d, J = 4 Hz, 1 H), 1.59–1.21 (m,
12 H), 1.02–0.81 (m, 15 H), 0.15 (s, 9 H).
Anal. Calcd for C30H58OSiSn: C, 59.10; H, 9.59. Found: C, 59.35;
H, 9.41.
(Z)-(3-Allyloxy-3-phenyl-2-tributylstannylpropenyl)trimethyl-
silane (4c)
Yield: 61%; colorless oil.
IR (neat): 2955, 1448, 1247, 1069, 861, 837, 744, 698 cm–1.
13C NMR (75 MHz, CDCl3): d = 166.4, 142.4, 136.8, 131.2, 130.8,
128.5, 127.6, 126.5, 83.1, 29.2, 27.5, 13.6, 11.9, 0.3.
Anal. Calcd for C26H46OSiSn: C, 59.89; H, 8.89. Found: C, 60.01;
H, 9.14.
1H NMR (300 MHz, CDCl3): d = 7.35–7.19 (m, 5 H), 6.56 [d, J = 1
Hz, J(119Sn,H) = 168 Hz, J(117Sn,H) = 161 Hz, 1 H], 6.04–5.90 (m,
1 H), 5.30 (ddt [app. ddd], J = 17, 4, 2 Hz, 1 H), 5.17 (ddt, J = 11,
4, 2 Hz, 1 H), 4.81 [d, J = 2 Hz, J(Sn,H) = 46 Hz, 1 H], 4.07 (dddd,
J = 13, 5, 2, 2 Hz, 1 H), 3.92 (dddd, J = 13, 6, 2, 2 Hz, 1 H), 1.43–
1.15 (m, 12 H), 0.94–0.70 (m, 15 H), 0.18 (s, 9 H).
(Z)-2-Tributylstannyl-1-trimethylsilyloct-1-en-3-ol (3h)
Yield: 74%; colorless oil.
IR (neat): 3452, 2956, 2928, 1464, 1247, 1026, 860, 736 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.51 [d, J = 1 Hz, J(119Sn,H) = 174
Hz, J(117Sn,H) = 166 Hz, 1 H], 4.06 (m, 1 H), 1.58–1.25 (m, 20 H),
1.03–0.82 (m, 18 H), 0.13 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 168.8, 140.4, 83.0, 37.0, 31.8, 29.3,
27.5, 25.6, 22.6, 14.0, 13.7, 11.8, 0.3.
13C NMR (75 MHz, CDCl3): d = 165.8, 145.3, 141.0, 135.1, 127.9,
127.2, 127.1, 116.2, 92.0, 69.5, 29.1, 27.5, 13.7, 11.8, 0.4.
Anal. Calcd for C27H48OSiSn: C, 60.55; H, 9.05. Found: C, 60.61;
H, 8.76.
Synthesis 2004, No. 9, 1381–1390 © Thieme Stuttgart · New York

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T. E. Nielsen et al.
PAPER
(Z)-(3-Methoxy-3-phenyl-2-tributylstannylpropenyl)trimethyl-
silane (4d)
TBAF-Mediated Desilylation of Silastannation Products; Gen-
eral Procedure
Yield: >95%; colorless oil.
IR (neat): 2955, 1464, 1376, 1248, 1092, 839, 743, 699 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.35–7.20 (m, 5 H), 6.53 [d, J = 2
Hz, J(119Sn,H) = 170 Hz, J(117Sn,H) = 162 Hz], 4.64 [s,
J(Sn,H) = 42 Hz, 1 H], 1.45–1.17 (m, 12 H), 1.00–0.68 (m, 15 H),
0.17 (s, 9 H).
To a solution of the silastannane 4f,g (1.09 mmol) in THF (1 mL)
was added Bu4NF (1.0 M in THF, 3.3 mL, 3.3 mmol). The reaction
mixture was refluxed overnight, and partitioned between H2O (20
mL) and Et2O (20 mL). The organic phase was separated, and the
aqueous phase was extracted with Et2O (2 × 20 mL). The combined
organic phases were dried (MgSO4), filtered, and rotary evaporated.
The residue was purified by flash column chromatography on silica
gel (hexane–EtOAc–Et3N, 50:1:1–50:2:1) to give the desilylated
product.
13C NMR (75 MHz, CDCl3): d = 166.0, 144.7, 140.8, 127.9, 127.3,
127.1, 94.0, 56.5, 29.0, 27.5, 13.7, 11.8, 0.4.
Anal. Calcd for C25H46OSiSn: C, 58.94; H, 9.10; Found: C, 58.99;
H, 9.12.
Tributyl-{1-[(2-methoxyethoxymethoxy)phenylmethyl]vi-
nyl}stannane (6)
Yield: 85%; colorless oil.
IR (neat): 2955, 2926, 1457, 1110, 1038, 929, 699 cm–1.
(Z)-[3-(2-Methoxyethoxymethoxy)-3-phenyl-2-tributylstannyl-
propenyl]trimethylsilane (4f)
1H NMR (300 MHz, CDCl3): d = 7.35–7.19 (m, 5 H), 5.94 [dd,
J = 2, 2 Hz, J(Sn,H) = 126 Hz, 1 H], 5.38 [dd, J = 2, 1 Hz,
J(Sn,H) = 60 Hz, 1 H], 5.25 [br s, J(Sn,H) = 21 Hz, 1 H], 4.81 (d,
J = 7 Hz, 1 H), 4.72 (d, J = 7 Hz, 1 H), 3.72–3.66 (m, 2 H), 3.53–
3.46 (m, 2 H), 3.36 (s, 3 H), 1.45–1.15 (m, 12 H), 0.90–067 (m, 15
H).
Yield: 88%; colorless oil.
IR (neat): 2956, 1456, 1376, 1248, 1110, 1026, 839, 744, 700 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.37–7.20 (m, 5 H), 6.74 [d, J = 1
Hz, J(119Sn,H) = 167 Hz, J(117Sn,H) = 160 Hz, 1 H], 5.19 [s,
J(Sn,H) = 41 Hz, 1 H], 4.86 (d, J = 7 Hz, 1 H), 4.76 (d, J = 7 Hz, 1
H), 3.87–3.79 (m, 1 H), 3.73–3.64 (m, 1 H), 3.55 (t, J = 5 Hz, 2 H),
3.39 (s, 3 H), 1.38–1.15 (m, 12 H), 0.96–0.70 (m, 15 H), 0.19 (s, 9
H).
13C NMR (75 MHz, CDCl3): d = 155.7, 141.4, 128.1, 127.1, 126.9,
126.0, 92.7, 83.7, 71.7, 67.0, 58.9, 28.9, 27.3, 13.6, 9.9.
13C NMR (75 MHz, CDCl3): d = 163.9, 145.9, 140.7, 128.0, 127.1
(two signals), 92.7, 88.1, 71.8, 67.1, 59.0, 53.4, 28.9, 27.4, 13.6,
11.7, 0.3.
Anal. Calcd for C25H44O3Sn: C, 58.72; H, 8.67. Found: C, 58.89; H,
8.58.
Tributyl[1-(methoxynaphth-1-ylmethyl)vinyl]stannane (7)
Yield: 89%; colorless oil.
Anal. Calcd for C28H52O3SiSn: C, 57.63; H, 8.98. Found: C, 57.78;
H, 8.74.
IR (neat): 2954, 2925, 1464, 1376, 1101, 1094, 927, 801, 779, 699
cm–1.
1H NMR (300 MHz, CDCl3): d = 8.18–8.10 (m, 1 H), 7.89–7.77 (m,
2 H), 7.53–7.40 (m, 4 H), 5.58 [dd (app. t), J = 2, 3 Hz,
J(Sn,H) = 134 Hz, 1 H], 5.32 [m, J(Sn,H) = 64 Hz, J(Sn,H) = 26
Hz, 2 H], 3.31 (s, 3 H), 3.55–1.20 (m, 12 H), 0.95–0.67 (m, 15 H).
13C NMR (75 MHz, CDCl3): d = 157.4, 136.9, 134.1, 131.2, 128.5,
128.2, 125.8, 125.4, 125.2 (two signals), 125.1, 88.2, 56.4, 29.1,
27.0, 13.7, 10.1.
(Z)-[3-Methoxy-3-(naphth-1-yl)-2-tributylstannylpropenyl]tri-
methylsilane (4g)
Yield: >95%; colorless oil.
IR (neat): 2955, 2921, 1464, 1247, 1089, 862, 776, 674 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.09–8.01 (m, 1 H), 7.89–7.74 (m,
2 H), 7.53–7.38 (m, 4 H), 6.37 [d, J = 2 Hz, J(119Sn,H) = 176 Hz,
J(117Sn,H) = 168 Hz, 1 H], 5.38 [d, J = 2 Hz, J(Sn,H) = 19 Hz, 1 H],
3.33 (s, 3 H), 1.53–1.16 (m, 12 H), 1.05–0.75 (m, 15 H), 0.18 (s, 9
H).
13C NMR (75 MHz, CDCl3): d = 164.6, 143.4, 136.1, 134.1, 131.8,
131.8, 128.5, 128.5, 126.8, 125.5, 125.3, 125.1, 124.9, 89.7, 57.0,
29.2, 27.5, 13.7, 11.7, 0.2.
Anal. Calcd for C26H40OSn: C, 64.08; H, 8.27. Found: C, 64.08; H,
8.32.
Iododestannylation of Alkenylstannanes; General Procedure
A solution of the alkenylstannane 6, 7 (0.50 mmol) in CH2Cl2 (40
mL) was cooled to 0 °C, and a solution of I2 (ca. 130 mg, 0.5 mmol)
in CH2Cl2 (15 mL) was added dropwise until a permanent red col-
oration was observed. The reaction mixture was stirred for a further
30 min, before pouring the mixture into aq sat. Na2S2O3 (15 mL).
The red/pink organic phase became immediately colorless when
shaken with aq sat. Na2S2O3 in a separating funnel. The organic
phase was washed with further amounts of aq sat. Na2S2O3 (2 × 10
mL) and brine (5 mL), then separated, dried (MgSO4), and rotary
evaporated. The residue was purified by flash column chromatogra-
phy on silica gel (hexane–EtOAc, 30:1) to give the alkenyl iodide.
Anal. Calcd for C29H48OSiSn: C, 62.26; H, 8.65. Found: C, 62.69;
H, 8.43.
(Z)-[3-(2-Bromobenzyloxy)-2-tributylstannylpropenyl]trimeth-
ylsilane (4h)
Yield: 78%; colorless oil.
IR (neat): 2955, 1464, 1376, 1339, 1097, 1028, 847, 748, 691, 670
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.55–7.50 (m, 2 H), 7.34–7.28 (m,
1 H), 7.17–7.10 (m, 1 H), 6.69 [t, J = 1 Hz, J(119Sn,H) = 169 Hz,
J(117Sn,H) = 161 Hz, 1 H], 4.54 (s, 2 H), 4.21 [d, J = 1 Hz,
J(Sn,H) = 32 Hz, 2 H], 1.55–1.24 (m, 12 H), 1.10–0.84 (15 H, m),
0.15 (s, 9 H).
[2-Iodo-1-(2-methoxyethoxymethoxy)allyl]benzene (8)
Yield: 88%; colorless oil.
IR (neat): 2886, 1611, 1494, 1452, 1274, 1112, 1024, 912, 852, 760,
700 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.43–7.28 (m, 5 H), 6.54 (dd,
J = 1, 2 Hz, 1 H), 6.04 (dd, J = 1, 2 Hz, 1 H), 5.03 (s, 1 H), 4.86 (d,
J = 7 Hz, 1 H), 4.78 (d, J = 7 Hz, 1 H), 3.82–3.68 (m, 2 H), 3.60–
3.46 (m, 2 H), 3.36 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 161.2, 144.6, 138.0, 132.2, 128.8,
128.5, 127.2, 122.2, 82.8, 71.0, 29.2, 27.5, 13.7, 11.2, 0.1.
Anal. Calcd for C25H45BrOSiSn: C, 51.04; H, 7.71. Found: C,
51.30; H, 7.80.
Synthesis 2004, No. 9, 1381–1390 © Thieme Stuttgart · New York

PAPER
Pd-Catalyzed Silastannation of Propargylic Alcohols
1389
13C NMR (75 MHz, CHCl3): d = 138.5, 128.2, 128.0, 127.6, 127.1,
113.4, 92.9, 82.1, 71.6, 67.4, 58.9.
Acknowledgment
The Technical University of Denmark is gratefully acknowledged
for financial support. TEN thanks Jens M. J. Nolsøe and Jacob Ko-
foed for experimental assistance.
Anal. Calcd for C13H17IO3: C, 44.84; H, 4.92. Found: C, 44.91; H,
4.87.
1-(2-Iodo-1-methoxyallyl)naphthalene (9)
Yield: 95%; colorless oil.
References
IR (neat): 2925, 1606, 1511, 1460, 1396, 1190, 1095, 910, 802, 785,
733 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.08–8.00 (m, 1 H), 7.93–7.82 (m,
2 H), 7.73–7.66 (m, 1 H), 7.57–7.45 (m, 3 H), 6.46 (dd, J = 2, 2 Hz,
1 H), 6.09 (dd, J = 1, 2 Hz, 1 H), 5.25 (s, 1 H), 3.49 (s, 3 H).
(1) Review: Beletskaya, I.; Moberg, C. Chem. Rev. 1999, 99,
3435.
(2) For an overview, see: Metal-Catalyzed Cross-Coupling
Reactions; Diederich, F.; Stang, P. J., Eds.; Wiley-VCH:
New York, 1998, .
(3) For selected reviews on the Stille reaction, consult:
(a) Stille, J. K. Angew Chem., Int. Ed. Engl. 1986, 25, 508.
(b) Mitchell, T. N. Synthesis 1992, 803. (c) Farina, V.;
Krishnamurthy, V.; Scott, W. J. Org. React. 1998, 50, 1.
(d) Duncton, M. A. J.; Pattenden, G. J. Chem. Soc., Perkin
Trans. 1 1999, 1235.
(4) For selected reviews on the Suzuki reaction, consult:
(a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(b) Chemler, S. R.; Trauner, D.; Danishefsky, S. J. Angew.
Chem. Int. Ed. 2001, 40, 4544. (c) Kotha, S.; Lahiri, K.;
Kashinath, D. Tetrahedron 2002, 58, 9633.
(5) Mitchell, T. N.; Killing, H.; Dicke, R.; Wickenkamp, R. J.
Chem. Soc., Chem. Commun. 1985, 354.
(6) Chenard, B. L.; Laganis, E. D.; Davidson, F.; RajanBabu, T.
V. J. Org. Chem. 1985, 50, 3666.
(7) Mitchell, T. N.; Wickenkamp, R.; Amamria, A.; Dicke, R.;
Schneider, U. J. Org. Chem. 1987, 52, 4868.
(8) Murakami, M.; Morita, Y.; Ito, Y. J. Chem. Soc., Chem.
Commun. 1990, 428.
13C NMR (75 MHz, CHCl3): d = 134.1, 133.9, 131.2, 129.3, 129.2,
128.3, 126.4, 126.2, 125.8, 125.5, 123.7, 112.5, 86.6, 57.8.
Anal. Calcd for C14H13IO: C, 51.87; H, 4.04. Found: C, 51.62; H,
4.31.
Stille Reactions of Alkenylstannanes; General Procedure
A Schlenk tube was charged with LiCl (127 mg, 3.0 mmol) and
flame-dried under high vacuum. Upon cooling, Ph3P (52 mg, 0.20
mmol), tris(dibenzylideneacetone)dipalladium(0)-CHCl3 complex
(52 mg, 0.05 mmol), and CuCl (245 mg, 2.5 mmol) were added, and
the mixture was degassed (4 ×) under high vacuum with an argon
purge. A solution of iodobenzene (100 mg, 0.5 mmol), and the alk-
enylstannane 3d, 6 (0.6 mmol) in DMSO (5 mL) was introduced
with concomitant stirring. The reaction mixture was vigorously de-
gassed (4 ×) by the freeze-pump-thaw process (–78 °C to r.t., ar-
gon). The mixture was stirred at r..t for 1 h, and then heated to 60
°C overnight. Upon cooling, the mixture was diluted with Et2O (60
mL), and washed with a mixture of brine (80 mL) and 5% aq am-
monia (15 mL). The aqueous layer was further extracted with Et2O
(2 × 50 mL), and the combined organic layers were washed with
H2O (2 × 50 mL, brine (2 × 50 mL), then dried (MgSO4), filtered,
and concentrated by rotary evaporation. The residue was purified by
flash column chromatography on silica gel (hexane–EtOAc, 20:1)
to give the cross-coupling product.
(9) Murakami, M.; Amii, H.; Takizawa, N.; Ito, Y.
Organometallics 1993, 12, 4223.
(10) Casson, S.; Kocienski, P.; Reid, G.; Smith, N.; Street, J. M.;
Webster, M. Synthesis 1994, 1301.
(11) Minière, S.; Cintrat, J.-C. Synthesis 2001, 705.
(12) Hada, M.; Tanaka, Y.; Ito, M.; Murakami, M.; Amii, H.; Ito,
Y.; Nakatsuji, H. J. Am. Chem. Soc. 1994, 116, 8754.
(13) See for example: (a) Colvin, E. W. Silicon in Organic
Synthesis; Butterworths: London, 1981. (b) Weber, W. P.
Silicon Reagents for Organic Synthesis; Springer-Verlag:
New York, 1983. (c) The Chemistry of Silicon Compounds;
Patai, S.; Rappoport, Z., Eds.; Wiley: Chichester, 1989.
(14) See for example: (a) Pereyre, M.; Quintard, J.-P.; Rahm, A.
Tin in Organic Synthesis; Butterworths: London, 1987.
(b) Chemistry of Tin; Smith, P. J., Ed.; Blackie Academic &
Professional: New York, 1998. (c) Davies, A. G. Organotin
Chemistry; VCH: Weinheim, 1997.
(E)-1,2-Diphenyl-3-trimethylsilylprop-2-en-1-ol (10)
Yield: 67%; colorless oil.
IR (neat): 3375, 2954, 1595, 1490, 1246, 1061, 877, 838, 764, 700
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.68–7.50 (8 H, m), 7.30–7.21 (2
H, m), 6.47 (1 H, d, J = 2 Hz), 5.74 (1 H, dd, J = 4, 2 Hz), 2.47 (1
H, d, J = 4 Hz), 0.19 (9 H, s).
13C NMR (75 MHz, CDCl3): d = 159.3, 141.5, 140.5, 129.1, 128.2,
127.6 (two peaks), 127.2, 126.9, 126.4, 79.7, –0.1.
(15) Chenard, B. L.; Van Zyl, C. M. J. Org. Chem. 1986, 51,
3561.
Anal. Calcd for C18H22OSi: C, 76.54; H, 7.85. Found: C, 76.88; H,
7.99.
(16) For studies on Stille reactions of silastannation products,
see: (a) Chenard, B. L.; Van Zyl, C. M.; Sanderson, D. R.
Tetrahedron Lett. 1986, 27, 2801. (b) Lunot, S.; Thibonnet,
J.; Duchêne, A.; Parrain, J.-L.; Abarbri, M. Tetrahedron
Lett. 2000, 41, 8893. (c) Timbart, L.; Cintrant, J.-C. Chem.–
Eur. J. 2002, 8, 1637.
(17) Ikenaga, K.; Hiramatsu, K.; Nasaka, N.; Matsuto, S. J. Org.
Chem. 1993, 58, 5045.
(18) Midland, M. M. J. Org. Chem. 1975, 40, 2250.
(19) In subsequent experiments we noted that the catalyst loading
could generally be reduced to amounts as low as 0.1% Pd,
with only minor loss in product yield..
{1-[Phenyl(2-methoxyethoxymethoxy)methyl]vinyl}benzene
(11)41
Yield: 81%; yellow oil.
IR (neat): 2925, 1457, 1377, 1260, 1172, 1106, 1040, 909, 734, 698
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.48–7.10 (m, 10 H), 5.67 (br s, 1
H), 5.52 (d, J = 1 Hz, 1 H), 5.46 [dd (app. t), J = 1, 1 Hz, 1 H], 4.87
(d, J = 7 Hz, 1 H), 4.77 (d, J = 7 Hz, 1 H), 3.72–3.65 (m, 2 H), 3.55–
3.47 (m, 2 H), 3.39 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 148.1, 143.2, 128.2 (several sig-
nals), 127.4, 127.1, 115.3, 93.1, 79.0, 71.7, 67.2, 58.9.
(20) Review: Smith, N. D.; Mancuso, J.; Lautens, M. Chem. Rev.
2000, 100, 3257.
(21) (a) Greeves, N.; Torode, J. S. Synlett 1994, 537.
(b) Nielsen, T. E.; Tanner, D. J. Org. Chem. 2002, 67, 6366.
Synthesis 2004, No. 9, 1381–1390 © Thieme Stuttgart · New York

1390
T. E. Nielsen et al.
PAPER
(22) Kazmaier, U.; Schauss, D.; Pohlman, M. Org. Lett. 1999, 1,
1017.
(31) Feldman, K. S.; Bruendl, M. M.; Schildknegt, K.; Bohnstedt,
A. C. J. Org. Chem. 1996, 61, 5440.
(23) Ritter, K. Synthesis 1989, 218.
(32) Darcel, C.; Bruneau, C.; Dixneuf, P. H.; Roberts, S. M.
Tetrahedron 1997, 53, 9241.
(33) Bernassau, J. M.; Bertranne, M.; Collongues, C.; Fetizon, M.
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(34) Garratt, D. G.; Beaulieu, P. L.; Morisset, V. M. Can. J.
Chem. 1981, 59, 927.
(35) Nash, B. W.; Thomas, D. A.; Warburton, W. K.; Williams,
T. D. J. Chem. Soc. 1965, 2983.
(24) For the first reports on Cu(I)-mediated Stille reactions,
consult: (a) Marino, J. P.; Long, J. K. J. Am. Chem. Soc.
1988, 110, 7916. (b) Liebeskind, L. S.; Fengl, R. J. Org.
Chem. 1990, 55, 5359.
(25) (a) Quayle, P.; Wang, J.; Xu, J.; Urch, C. J. Tetrahedron Lett.
1998, 39, 489. (b) Flohr, A. Tetrahedron Lett. 1998, 39,
5177.
(26) Han, X.; Stoltz, B. M.; Corey, E. J. J. Am. Chem. Soc. 1999,
121, 7600.
(36) Diyne 1j was prepared according to the general procedure
with the modification that 25 mmol of ethyl benzoate was
treated with 55 mmol of lithium acetylide.
(37) Glaenzer, B. I.; Faber, K.; Griengl, H. Tetrahedron 1987, 43,
5791.
(38) Smulik, J. A.; Diver, S. T. Org. Lett. 2000, 2, 2271.
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(40) Moorthy, B. K. J. Indian Chem. Soc. 1990, 67, 909.
(41) A satisfactory elemental analysis could not be obtained due
to the presence of an inseparable amount (<5%) of
dibenzylideneacetone (dba).
(27) Österlöf, J. Acta Chim. Scand. 1950, 4, 374.
(28) At 1 atm, 1 mole of ideal gas has a volume of approximately
23 L. Therefore, considering acetylene as an ideal gas, 1 L of
acetylene should correspond to app. 43 mmol. This need not
to be more accurate, as long as an excess of acetylene
relative to BuLi is assured.
(29) Mortier, J.; Vaultier, M.; Carreaux, F.; Douin, J. J. Org.
Chem. 1998, 63, 3515.
(30) Henderson, M. A.; Heathcock, C. H. J. Org. Chem. 1988, 53,
4736.
Synthesis 2004, No. 9, 1381–1390 © Thieme Stuttgart · New York