Gold(III)-catalyzed direct nucleophilic substitution of propargylic alcohols

Article abstract of DOI:10.1016/j.tet.2008.12.051

Gold-catalyzed nucleophilic substitution of propargylic alcohols with various nucleophiles (allylsilane, electron-rich aromatics, alcohols, thiols, hydrides, 1,3-dicarbonyl derivatives, sulfonamides) is described under very mild conditions (room temperatu

Full text of DOI:10.1016/j.tet.2008.12.051

Tetrahedron 65 (2009) 1758–1766
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Gold(III)-catalyzed direct nucleophilic substitution of propargylic alcohols
a
a
b
b
b,
*
´
Marie Georgy , Valerie Boucard , Olivier Debleds , Christophe Dal Zotto , Jean-Marc Campagne
a Institut de Chimie des Substances Naturelles, UPR 2301, Avenue de la Terrasse, 91198 Gif sur Yvette, France
b Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-UM2-UM1-ENSCM, 8 rue de l’Ecole Normale, 34296 Montpellier, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 June 2008
Received in revised form 24 October 2008
Accepted 26 October 2008
Available online 24 December 2008
Gold-catalyzed nucleophilic substitution of propargylic alcohols with various nucleophiles (allylsilane,
electron-rich aromatics, alcohols, thiols, hydrides, 1,3-dicarbonyl derivatives, sulfonamides) is described
under very mild conditions (room temperature in dichloromethane). Preliminary mechanistic in-
vestigations suggest a mechanism through a carbocation intermediate. Nucleophilic substitutions on
allylic and benzylic alcohols are also described.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
using acetone, hydrides, and electron-rich aromatic nucleophiles.5
The use of monoruthenium complexes was then described by
The direct (i.e., with non-pre-activated good leaving groups)
substitution of propargylic alcohols (Scheme 1) has been for years
a relatively unexplored reaction compared to reactions on allylic
and benzylic substrates. These reactions are particularly interesting
in the current context of the development of greener and atom-
economic reactions because water is thus generated as the only by-
product. These reactions have been traditionally carried under
Nicholas conditions, using cobalt stabilized carbocations. However,
the so-called Nicholas reaction requires a multi-step sequence and
a stoichiometric amount of [Co2(CO)8].1 The development of
greener catalytic reactions was thus highly desirable.
Cadierno and Dixneuf.6
In 2003, oxo-rhenium catalysts have been described by Toste et
al.7–10 Substitution products are obtained in high yields with
alcohols, allylsilanes, aromatics, and nitrogen nucleophiles. In-
terestingly, these reactions were not limited to ‘true’ propargylic
alcohols. This methodology has been further used in a formal
synthesis of podophyllotoxin.10 The use of [ReBr(CO)3(THF)]2 was
more recently described (in 2007) by Takai et al.11
In 2005, we described the direct Au(III)-catalyzed substitution of
propargylic alcohols in the presence of various nucleophiles (allylsi-
lanes, alcohols, thiols, electron-rich aromatics), and showed that gold
probably acts as a Lewis acid to promote the formation of a stabilized
propargylic carbocation intermediate.12 A related reaction was sub-
sequently reported by Dyker et al. in 2006, using azulene and 1,3-
dimethoxybenzene in Friedel–Crafts type reactions with benzylic
and propargylic alcohols.13 Shortly after, Sanz and Zhan described
that these reactions could also be carried out under Brønsted acid and
FeCl3 catalysis, respectively.14–17 Later on, the use of copper, indium,
bismuth, scandium, ytterbium, phosphomolybdic acid, and iodine
catalysts has been reported by several groups.18 These aspects have
been recently reviewed by Kabalka et al.19 A conceptually different
approach, through the reaction of a propargylic alkoxide with allyl-
silane or organoboron dihalides, was also reported by Kabalka et al.20
We would like to give herein a full account on our work related to
gold(III)-catalyzed direct propargylic substitution.
OH
Nu
R1
R2
cat.
R1
R2
+
H2O
Nu-H
R3
R3
Scheme 1.
In 1994, Murahashi et al.2 described, in a seminal paper, the
propargylic substitution of monosubstituted (R3¼H) alkynes bear-
ing a good leaving group on the propargylic alcohol moiety, where
a mechanism through a copper–allenylidene intermediate was
postulated.3 Hidai et al. have there after developed a diruthenium
complex catalyst for the direct substitution of ‘true’ (R3¼H) prop-
argylic alcohols, in the presence of a large number of heteroatomic
(alcohols, hydrides, amines, thiols, nitrogen, phosphorus,.) and
carbon-centered nucleophiles.4 Using enantiomerically pure cata-
lysts, asymmetric propargylic substitutions were next developed
2. Results
The initial starting point of this work is connected to early at-
tempts to develop a strategy for the construction of the C13–C19
fragment of macrolactine A.21 We initially planned to construct this
fragment by applying an enantioselective alkynylation,22 followed
* Corresponding author.
E-mail address: jean-marc.campagne@enscm.fr (J.-M. Campagne).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.12.051

M. Georgy et al. / Tetrahedron 65 (2009) 1758–1766
1759
OH
13
13
O
O
HO
19
13
O
19
HO
Evans'
HO
19
PO
Hydride
HO
B
C
Macrolactine A
triple bond
hydration
19
13
+
OHC
A
Enantioselective
alkynylation
19
PO
+ alcohol protection
Scheme 2.
by a regioselective triple bond hydration to give the aldol surrogate
B.23 Finally, the
-keto alcohol could be reduced under Evans
Table 1
b
conditions24 to give the C13–C15 1,3-anti diol C (Scheme 2).
We initially tested the triple bond hydration on model substrate
1, obtained from the reaction between sorbaldehyde and heptyne,
where the propargylic alcohol was further protected as a TIPS ether.
When the hydration reaction was carried out in the presence of
Au(III) catalyst, under Utimoto conditions,23 the expected ketone 2
could not be isolated. The only, rather unexpected, isolated (in 72%
yield) product was 3 resulting from the formal SN0 substitution of
the OTIPS functional group by methanol (Scheme 3). We thus an-
ticipated that gold(III) might be an interesting catalyst in the direct
nucleophilic substitution of propargylic alcohols (Scheme 1).
Entry
Gold cat (%)
Time (H)
Isolated yield
of 5 (%)
1
2
3
4
5
6
7
8
9
NaAuCl4$2H2O (5)
AuBr3 (5)
AuCl3 (5)
HAuCl4$3H2O (5)
AuCl
Ph3PAuCl
PdCl2(PhCN)2 (5)
PtCl2 (5)
NaAuCl4$2H2O (1)
12
12
12
12
12
12
12
12
2
82
68
65
60þ6 (11%)
30
NR
NR
NR
71
furnish 6 as the major product. After some experimentation, we
ended up with two different sets of conditions: (i) in the presence
of both AuCl3 (5 mol %) and Ph3PAuSbF6 (5 mol %) catalysts, a 30:70
mixture of compounds 5 and 6 was obtained; (ii) a selective for-
mation of 6, isolated in 71% yield, was only achieved when the
reaction mixture was first treated by AuCl3 (5 mol %) to complete
(TLC monitoring) the substitution reaction, and then by Ph3PAuSbF6
(5 mol %) to promote the cycloisomerization (Scheme 5). Similar
experiments have been reported by Toste et al.25 and more recently
by Sanz et al.16
TIPSO
O
n-pent
2 (not isolated)
OTIPS
NaAuCl4.2H2O 5 mol%
MeOH/H2O 10:1, t. a. 1h
n-pent
OMe
1
n-pent
72%
3
Scheme 3.
The proof of concept was thus tested in the model reaction of 4
with allyltrimethylsilane in the presence of various gold(III) and
gold(I) sources (Scheme 4, Table 1).
SiMe3
cat.
Ph
+
4
n-pent
Ph
CH2Cl2, rt
n-pent
6
5
Au cat.
OH
AuCl3 5%
+
+
Allyl-TMS
30
70
64% (5+6)
4
Ph
Ph
Ph
CH2Cl2, rt
Ph3PAuSbF6 5%
6
4
4
4
5
AuCl3 5%, 5h
then
--
100
71%
Scheme 4.
Ph3PAuOTf 5%
Gratifyingly, the expected product 5 could be isolated in good
yields using various Au(III) catalysts (Table 1, entries 1–4), whereas
more disappointing results have been obtained in the presence of
Au(I) catalysts (Table 1, entries 5 and 6) and no reaction observed
with PtCl2 and PdCl2(PhCN)2 catalysts (Table 1, entries 7 and 8).
After a short optimization, in the presence of NaAuCl4$2H2O
(1 mol %) and after 2 h at room temperature, compound 5 was
isolated in 71% yield (Table 1, entry 9). In the presence of
HAuCl4$3H2O (Table 1, entry 4), the bicyclic compound 6, probably
resulting from the cycloisomerization of the 1,5-ene-yne 5,25,26 was
also isolated as a minor product (11% yield). We thus next focused
our efforts toward the development of reaction conditions able to
Scheme 5.
Starting from the model reaction with 4 and allyltrimethyl-
silane, we set out to define the scope of the Au(III)-catalyzed
propargylic substitutions. Variations on the aromatic group were
first examined. Various substituents (naphthyl, OMe, Br, F, Cl, Me,
Ph,.) are well tolerated (see compounds 5–16) to the exception of
the electron withdrawing nitro and CF3 groups (compounds 17 and
18) where no reaction could be observed (Scheme 6). These 1,5-
ene-ynes have then been further transformed into cyclobutenes
using an RCM reaction in the presence of the Grubbs–Hoveyda II
catalyst.27

1760
M. Georgy et al. / Tetrahedron 65 (2009) 1758–1766
NaAuCl4 5%
Allyl-TMS
CH2Cl2, rt
OH
Ar
Ar
2
2
n
n
4
NaAuCl4, 2H2O 5%
Allyl-TMS
OH
4
4
OCH3
4
CH2Cl2, rt
OCH3
4
4
21
8 85%
5 82%
7 83%
4
1
4
3
3
Br
10 81%
9 72%
11 87%
66%
(as a 2,2,1 inseparable mixture)
Scheme 8.
F
3
Cl
3
3
Ph
13 88%
12 70%
14 92%
isolated in 59% and 33%, respectively.28 However, using secondary
propargyl alcohols bearing an alkyl group at the propargyl position
(R1¼alkyl, R2¼H), no reaction is observed (see compound 29)
(Scheme 10).
3
4
HO
MeO
3
15 91%
16 90%
OH
Allyl-TMS 1.2 Eq.
Ph
Ph
NaAuCl4, 2H2O 5%
DCM, rt, 4 H
X
X
3
F3C
O2N
17 no reaction
18 no reaction
Scheme 6.
Ph
4
A double allylation reaction was also attempted on symmetrical
bis-propargylic alcohol 19, and the corresponding bis-allylated
compound 20 was obtained in 69% yield (Scheme 7).
4 82%
22 75%
Starting from a cinnamyl derivative 21 (Scheme 8), an in-
separable 2:2:1 mixture of
66% yield.
a, g(E), and g(Z) isomers was obtained in
SiMe3
CO2Et
Ph
23 71%
24 97%
Substitutions at the alkyne position were next investigated.
Starting from alkyl, aromatic, and silyl substituents on the alkyne
position (R3¼alkyl, Ph, SiMe3), the corresponding allylated com-
pounds 4, 22–24 were isolated in 71–97% yield. Limitations of this
methodology were found with carboxylic esters substituents and
‘true’ alkynes where no reaction and a poor 9% yield were observed
(compounds 25 and 26) (Scheme 9).
H
25 no reaction
Scheme 9.
26 9%
Finally, tertiary benzylic and non-benzylic (in the propargylic
position) substrates were investigated. Compounds 27 and 28 were
NaAuCl4 5%
Allyl-TMS
CH2Cl2, rt
OH
R2
R1
R2
R1
3
3
HO
R3
R3
Alk
H3C
OH
CH3
CH3
27 59%
R3
n-pent
Ph
3
3
28 33%
29 no reaction
19
20
Scheme 10.
Scheme 7.

M. Georgy et al. / Tetrahedron 65 (2009) 1758–1766
1761
Ar-H
R-X-H
NaAuCl4, 2H2O 5%
CH2Cl2, rt, 24h
OH
Nu
R2
Ar
NaAuCl4, 2H2O 5%
CH2Cl2, rt., 24h
R1
R2
R1
R1
R1
R2
R2
R3
R3
R3
R3
OCH3
OCH3
O
O
O
Cl
O
Ph
H3C
Ph
CH3
OCH3
SiMe3
Ph
4
37 75%
38 79%
Ph
36 88%
SiMe3
Ph
BocNH
COOEt
CO2Et
31 75%
32 46%
30 65%
Ph
p/o,m 10:1
S
S
S
Scheme 11.
Ph
39 50%
Ph
Ph
Ph
Ph
4
41 35%
40 66%
The Au(III)-catalyzed reaction was next tested for a diverse
collection of nucleophiles. Carbon-centered nucleophiles were first
examined: electron-rich aromatics, including the acid-sensitive
furan, can be introduced in moderate to good yields and selectiv-
ities, at room temperature (Scheme 11).
The introduction of 1,3-dicarbonyl derivatives required harsher
reaction conditions. Whereas no reaction occurs at room temper-
ature, in refluxing dichloroethane, the expected product 33 could
not be isolated and a mixture of the triple bond hydration product
34 and furan 35 were isolated in 69% and 26% yields, respectively.
This result is in sharp contrast with results obtained by Sanz et al.
using PTSA catalyst where substitution products, such as 33, are
obtained selectively (Scheme 12).15
Moving to heteroatomic (O–, N–, and S–) nucleophiles, alcohols,
thiols, and sulfonamides could be successfully introduced and
compounds 36–42 were isolated in moderate to good yields. In the
presence of Boc-Cys-OEt, a 1:1 inseparable mixture of the two
possible diastereoisomers was obtained (Scheme 13).
Reactions with ethanol are more tricky, since unwanted Meyer–
Schuster29 rearranged by-products 44 and 45 are isolated as the
sole isolated products from alcohols 43 and 4, in 72% and 58%, re-
spectively. However, by decreasing the catalyst amount to 1%, the
expected ether 46 could be obtained in 60% yield, along with the
Meyer–Schuster product (35% yield) (Scheme 14).
SO2Ph
HN
Ph
42 58%
Scheme 13.
a mechanism through the formation of stabilized propargylic
carbocation (Scheme 17, Eq. b).
In order to test this hypothesis, the known30 enantiomerically
enriched (96% ee) propargylic alcohol (R)-50 was engaged in a re-
action in the presence of allyltrimethylsilane and Au(III) catalyst.
The corresponding allylated product was obtained in a racemic
form, thus suggesting a mechanism through the formation of
a carbocation intermediate (Scheme 18).
Ethanol
OH
O
NaAuCl4, 2H2O 5%
DCM, rt overnight
44 72%
Ph
Ph
Ph
Finally, reduction of the propargylic alcohols in the presence of
a hydride source was attempted. Indeed, in the presence of tri-
ethylsilane and NaAuCl4$2H2O 5 mol %, the corresponding re-
duction products were isolated in a 69–75% yield range (Scheme
15). Gratifyingly, polymethylhydrosiloxane (PMHS), a cheap and
stable polymeric by-product of the silicone industry, could also be
used in these reactions (Scheme 16).
43
OH
OEt
O
Ethanol
NaAuCl4, 2H2O
+
Ph
Ph
4
DCM, rt overnight
4
4
4
46
--
60%
45
The lack of reactivity in some examples prompts us to re-
consider our initial mechanistic proposal. In our initial thoughts, we
5% cat
1% cat
58%
35%
believed that gold may act, trough coordination to the
p-bond, as
a propargylic alcohol activating agent (Scheme 17, Eq. a). However,
Scheme 14.
the lack of reactions in compounds 17, 18, 25, and 29 suggested
O
O
O
O
O
O
O
OH
+
O
NaAuCl4, 2H2O 5%
DCE, reflux
O
33
not isolated
35
34
69 %
26%
Scheme 12.

1762
M. Georgy et al. / Tetrahedron 65 (2009) 1758–1766
H
OH
OH
PhSO2NH2
NaAuCl4, 2H2O 5%
NHSO2Ph
Et3Si-H 1.2 Eq.
NaAuCl4, 2H2O 5%
DCE, rt, 4 H
Ph
Ph
R'
R'
CH2Cl2, rt
58%
R
R
4
4
4
42
H
H
H
TsNH2
NaAuCl4, 2H2O 5%
OH
NHTs
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
n-Bu
n-Bu
CH2Cl2, rt
95%
51
47 69%
48 70%
49 75%
Scheme 15.
TsNH2
NaAuCl4, 2H2O 5%
OH
NHTs
Ph
Ph
CH2Cl2, rt
87%
52
53
TsNH2
NaAuCl4, 2H2O 5% Ph
OH
H
PMHS 1.2 Eq.
Ph
Ph
Ph
Ph
47 82%
NaAuCl4, 2H2O
DCE, t.a., 4 H
CH2Cl2, rt
83 %
OH
NHTs
Ph
Ph
55
54
Scheme 19.
Scheme 16.
3. Conclusion
In conclusion, we developed efficient gold(III)-catalyzed sub-
stitutions on propargylic, benzylic, and allylic alcohols. Similar re-
actions have also been recently reported to be catalyzed by simpler,
less expensive, catalysts such as FeCl3 or PTSA.14–16,34 Gold, how-
ever, allows reactions at room temperature and, due to the nature
of the metal, different selectivities can be expected as illustrated,
for example, by Dyker et al.13 These aspects are currently under
development in our laboratories. Another point of our current in-
terest in these reactions is the development of direct propargylic
substitutions, where the carbocation intermediate is not stabilized,
with, for example, secondary propargyl alcohols bearing an alkyl
group at the propargyl position (29). To the best of our knowledge,
only one example of these reactions has been reported to date.11
OH
HO
R1
Nu
NaAuCl4
R2
[Au]
R2
SN2 type ?
R1
(a)
(b)
R1
R2
Nu
R1
Nu
R3
SN1 type ?
R1
and / or
[Au]-
R2
R1
4. Experimental
R3
4.1. General information
Scheme 17.
Unless otherwise stated all commercial materials were used
without further purification. Reactions were carried out in round
bottom flasks equipped with a magnetic stirring bar and capped
with a septum. Dichloromethane was distilled over CaH2 and run
over neutral alumina to remove any residual ethanol. TLC analysis
of all reactions was performed on Merck silica gel 60 F254 TLC
plates. Chromatography was carried out on Merck 60 silica gel (35–
OH
SiMe3
NaAuCl4, 2H2O 5 mol%
CH2Cl2, t. a. 24h
Ph
Ph
(R)-50
24
70 mm). FTIR spectra were recorded with a Perkin Elmer Spectrum
BX spectrometer and Perkin Elmer Spectrum 1000. 1H and 13C NMR
spectra were recorded with Bruker Avance-300, Avance-500
spectrometers and Bruker Ultra shield 400 plus and referenced to
CDCl3 unless otherwise noted. Mass spectra, elemental, and chiral
HPLC analyses were obtained from the mass spectrometry, ele-
mental analysis and HPLC facilities operated by the Institut de
Chimie des Substances Naturelles and by the Centre Commun de
ee 96%
ee 0%
Scheme 18.
It thus appears that Au(III) catalyst may act as a Lewis Acid in
these reactions. Consequently, the presence of a triple bond in the
substrate is thus probably not necessary. Indeed, in collaboration
with the group of Prim et al.,31 the reactivity of benzylic alcohols
was also investigated and various nitrogen nucleophiles could be
introduced in these benzylic positions (Scheme 19).32 The reaction
of allylic alcohols was finally attempted. Starting from allylic
alcohol 54 and tosylamide, the corresponding substitution product
was isolated in 83% yield (Scheme 19).33
´
Spectrometrie de Masse of University Claude Bernard Lyon 1.
4.2. General procedure for gold-catalyzed nucleophilic
substitutions of propargylic alcohols
To a solution of propargylic alcohol (1 equiv) in dichloro-
methane or dichloroethane (0.2 M) was added the nucleophile

M. Georgy et al. / Tetrahedron 65 (2009) 1758–1766
1763
(1.5–5 equiv) followed by the catalyst (5 mol %). The reaction mix-
ture was stirred at room temperature and monitored periodically
by TLC. Upon completion, the mixture was concentrated in vacuo
and loaded on to a silica gel column and chromatographed with an
appropriate mixture of pentane and diethyl ether to give the sub-
stitution products described below.
4.2.6. 1-(Dec-1-en-5-yn-4-yl)-3-methylbenzene (10)
Prepared with 3 equiv of allyltrimethylsilane and isolated as
a colorless oil.
1H NMR (CDCl3, 400 MHz)
d
ppm 0.92 (t, J¼7.2 Hz, 3H),1.39–1.55
(m, 4H), 2.24 (dt, J¼2.1, 6.9 Hz, 2H), 2.35 (s, 3H), 2.45 (t, J¼7.2 Hz,
2H), 3.62 (tt, J¼2.2, 7.3 Hz, 1H), 5.03 (d, J¼9.9 Hz, 1H), 5.05 (d,
J¼17.0 Hz, 1H), 5.87 (tdd, J¼7, 10.2, 17.1 Hz, 1H), 7.03 (d, J¼7.1 Hz,
1H), 7.15 (t, J¼7.1 Hz,1H), 7.16 (s,1H), 7.21 (d, J¼7.3 Hz,1H); 13C NMR
4.2.1. Oct-1-en-5-yn-4-ylbenzene (5)12
Prepared with 1.5 equiv of allyltrimethylsilane and isolated as
a clear oil.
(CDCl3, 100 MHz)
d ppm 13.6, 18.5, 21.4, 21.9, 31.1, 37.9, 43.0, 81.1,
83.6, 116.5, 124.4, 127.2, 128.1 (2C), 135.9, 137.8, 142.1; HREIMS m/z
226.1720, calcd for C17H22 226.1722; IR (film) cmꢀ1 3077, 2952,
2228, 1689, 1642, 702.
1H NMR (CDCl3, 300 MHz)
d
ppm 0.92 (t, J¼7 Hz, 3H), 1.38 (m,
4H), 1.55 (m, 2H), 2.23 (td, J¼2.2, 7 Hz, 2H), 2.47 (t, J¼7 Hz, 2H), 3.68
(tt, J¼2.2, 7 Hz, 1H), 5.04 (d, J¼10.5 Hz, 1H), 5.05 (d, J¼16.8 Hz, 1H),
5.87 (ddt, J¼7, 10.4, 16.9 Hz, 1H), 7.20–7.39 (m, 5H); 13C NMR (CDCl3,
4.2.7. 1-(Dec-1-en-5-yn-4-yl)-2-methylbenzene (11)
Prepared with 3 equiv of allyltrimethylsilane and isolated as
a colorless oil.
75 MHz)
d ppm 14.2, 19.0, 22.4, 28.9, 31.2, 38.2, 43.2, 81.2, 84.0,
116.8,126.7,127.6, 128.5, 136.0, 142.3; MS (EI) m/z 185 (34), 91 (100),
77 (73), 41 (39). Anal. Calcd for C17H22: C, 90.20; H, 9.80. Found: C,
90.31; H, 10.15. IR (film) cmꢀ1 2955, 2929, 2357. Data are in accor-
dance with previously reported results.12
1H NMR (CDCl3, 400 MHz)
d
ppm 0.93 (t, J¼7.2 Hz, 3H),1.40–1.51
(m, 4H), 2.21 (dt, J¼2.2, 6.9 Hz, 2H), 2.34 (s, 3H), 2.41 (t, J¼7.1 Hz,
2H), 3.84 (tt, J¼2.2, 7.3 Hz, 1H, H7), 5.05 (d, J¼10.1 Hz, 1H), 5.08 (d,
J¼16.8 Hz, 1H), 5.91 (tdd, J¼7, 10.2, 17.1 Hz, 1H), 7.13 (m, 2H), 7.20
4.2.2. 1-Pentyl-3-phenylbicyclo[3.1.0]hex-2-ene (6)12
Prepared with 1.5 equiv of allyltrimethylsilane, 0.05 equiv
HAuCl4$3H2O and isolated as a colorless oil.
(m, 1H), 7.51 (d, J¼7.5 Hz, 1H); 13C NMR (CDCl3, 100 MHz)
d ppm
13.6, 18.5, 19.2, 21.9, 31.1, 34.4, 41.5, 81.3, 82.9, 116.4, 126.1, 126.4,
127.4, 130.2, 134.7, 136.0, 140.3; HREIMS m/z 226.1720, calcd for
C17H22 226.1722; IR (film) cmꢀ1 3075, 2956, 1684, 1640, 1605, 754.
1H NMR (CDCl3, 300 MHz)
d
ppm 0.26 (t, J¼3.8 Hz, 1H), 0.8 (dd,
J¼3.7, 8 Hz, 1H), 0.91 (t, J¼7 Hz, 3H), 1.32 (m, 4H), 1.46 (m, 3H), 1.67
(m, 1H), 2.70 (d, J¼17 Hz, 1H), 3.05 (ddd, J¼1.6, 7, 17 Hz, 1H), 6.32 (s,
4.2.8. 1-Chloro-4-(dec-1-en-5-yn-4-yl)benzene (12)
Prepared with 3 equiv of allyltrimethylsilane and isolated as
a colorless oil.
1H), 7.26–7.39 (m, 5H); 13C NMR (CDCl3, 75 MHz)
d ppm 14.1, 21.3,
22.7, 23.19, 28.2, 32.0, 33.4, 36.6, 36.9,125.1,126.6,128.3,132.3,136.8,
138.6. The compound decomposes rapidly at room temperature.
1H NMR (CDCl3, 400 MHz)
d
ppm 0.92 (t, J¼7.2 Hz, 3H), 1.37–1.54
(m, 4H), 2.23 (dt, J¼2.2, 6.9 Hz, 2H), 2.45 (t, J¼7.2 Hz, 2H), 3.64 (tt,
J¼2.2, 7.0 Hz, 1H), 5.02 (d, J¼16.8 Hz, 1H), 5.03 (d, J¼10.6 Hz, 1H),
5.81 (tdd, J¼7, 10.3, 17.0 Hz, 1H), 7.27 (s, 4H); 13C NMR (CDCl3,
4.2.3. 2-(Oct-1-en-5-yn-4-yl)naphthalene (7)12
Prepared with 1.5 equiv of allyltrimethylsilane and isolated as
a clear oil.
100 MHz)
d ppm 13.6, 18.4, 21.9, 31.0, 37.4, 42.9, 80.5, 84.1, 116.9,
1H NMR (CDCl3, 300 MHz)
d
ppm 0.93 (t, J¼7 Hz, 3H), 1.41 (m,
128.3 (2C), 128.8 (2C), 132.2, 135.3, 140.6; HREIMS m/z 246.1176,
calcd for C16H19Cl 246.1175; IR (film) cmꢀ1 3078, 2961, 1686, 1641,
1609, 810.
4H), 1.56 (m, 2H), 2.27 (td, J¼2.2, 7 Hz, 2H), 2.60 (t, J¼7 Hz, 2H), 3.85
(m, 1H), 5.05 (d, J¼10 Hz, 1H), 5.06 (d, J¼17 Hz, 1H), 5.90 (m, 1H),
7.47 (m, 3H), 7.8 (m, 4H); 13C NMR (CDCl3, 75 MHz)
d ppm 14.0,18.9,
22.2, 28.8, 31.1, 38.2, 42.9, 81.1, 84.1, 116.8, 125.5, 125.9, 126.0, 126.0,
4.2.9. 1-(Dec-1-en-5-yn-4-yl)-4-fluorobenzene (13)
Prepared with 3 equiv of allyltrimethylsilane and isolated as
a colorless oil.
127.6, 127.8, 128.0, 132.4, 133.5, 135.8, 139.6. Anal. Calcd for C21H24
:
C, 91.25; H, 8.75. Found: C, 91.17; H, 8.57. IR (film) cmꢀ1 3055, 2929.
Data are in accordance with previously reported results.12
1H NMR (CDCl3, 400 MHz)
d
ppm 0.92 (t, J¼7.2 Hz, 3H),1.38–1.55
(m, 4H), 2.23 (dt, J¼2.2, 7.0 Hz, 2H), 2.44 (t, J¼7.0 Hz, 2H), 3.65 (tt,
J¼2.1, 7.0 Hz, 1H), 5.03 (d, J¼11.2 Hz, 1H), 5.02 (d, J¼15.8 Hz, 1H),
5.89 (tdd, J¼7, 10.4 Hz, J¼16.6 Hz, 1H), 6.99 (m, 2H), 7.3 (m, 2H); 13C
4.2.4. 1,2-Dimethoxy-3-(oct-1-en-5-yn-4-yl)benzene (8)12
Prepared with 1.5 equiv of allyltrimethylsilane and isolated as
a clear oil.
NMR (CDCl3, 100 MHz)
d ppm 13.6, 18.4, 21.9, 31.1, 37.2, 43.1, 80.8,
1H NMR (CDCl3, 300 MHz)
d
ppm 0.92 (t, J¼7 Hz, 3H), 1.37 (m,
83.9,115.0 (d),116.7,128.9 (d),135.4,137.7,160.3,162.7; HREIMS m/z
230.1472, calcd for C16H19F 230.1471; IR (film) cmꢀ1 3077, 2958,
1641, 1602, 834.
4H), 1.54 (m, 2H), 2.22 (td, J¼2.2, 7 Hz, 2H), 2.45 (m, 2H), 3.86 (s,
3H), 3.87 (s, 3H), 4.10 (m,1H), 5.04 (d, J¼10 Hz,1H), 5.05 (d, J¼17 Hz,
1H), 5.90 (m, 1H), 6.80 (d, J¼1.5, 8 Hz, 1H), 7.05 (t, J¼8 Hz, 1H), 7.13
(dd, J¼1.6, 7.8 Hz, 1H); 13C NMR (CDCl3, 75 MHz)
d
ppm 14.0, 18.8,
4.2.10. 1-(Biphenyl-4-yl)hept-2-yn-1-ol (14)
Prepared with 3 equiv of allyltrimethylsilane and isolated as
a colorless oil.
22.2, 28.8, 31.1, 31.4, 41.8, 55.7, 60.8, 81.5, 82.8, 110.8, 116.4, 120.5,
123.8, 136.0, 136.2, 146.1, 152.5. Anal. Calcd for C19H26O2: C, 79.68;
H, 9.15. Found: C, 79.63; H, 9.28. IR (film) cmꢀ1 2929, 2359. Data are
in accordance with previously reported results.12
1H NMR (CDCl3, 400 MHz)
d
ppm 0.93 (t, J¼7.2 Hz, 3H),1.42–1.55
(m, 4H), 2.26 (dt, J¼2.2, 7.0 Hz, 2H), 2.51 (t, J¼7.2 Hz, 2H), 3.72 (tt,
J¼2.1, 7.1 Hz, 1H), 5.06 (d, J¼10.2 Hz, 1H), 5.08 (d, J¼17.1 Hz, 1H),
5.89 (tdd, J¼7, 10.2, 17.2 Hz, 1H), 7.33 (m, 1H), 7.43 (m, 4H), 7.56 (m,
4.2.5. 1-Bromo-3-(oct-1-en-5-yn-4-yl)benzene (9)12
Prepared with 1.5 equiv of allyltrimethylsilane and isolated as
a colorless oil.
4H); 13C NMR (CDCl3, 100 MHz)
d ppm 13.6, 18.5, 21.9, 31.1, 37.7,
43.0, 80.9, 83.8, 116.7, 127.0 (2C), 127.0 (3C), 127.8 (2C), 128.6 (2C),
135.7, 139.4, 140.9, 141.2; HREIMS m/z 288.1877, calcd for C22H24
288.1878; IR (film) cmꢀ1 3062, 2932, 1683, 1635, 1601, 735.
1H NMR (CDCl3, 300 MHz)
4H), 1.50 (m, 2H), 2.23 (td, J¼2.2, 7 Hz, 2H), 2.46 (t, J¼7 Hz, 2H), 3.64
(td, J¼2.1, 7 Hz, 2H), 5.04 (d, J¼10 Hz, 1H), 5.05 (d, J¼17 Hz, 1H), 5.84
(m, 1H), 7.23 (m, 1H), 7.37 (m, 2H), 7.52 (m, 1H); 13C NMR (CDCl3,
d
ppm 0.92 (t, J¼7 Hz, 3H), 1.37 (m,
4.2.11. 1-(Dec-1-en-5-yn-4-yl)-4-methoxybenzene (15)
Prepared with 3 equiv of allyltrimethylsilane and isolated as
a colorless oil.
75 MHz) d ppm 14.1, 18.9, 22.3, 28.8, 31.2, 37.8, 43.0, 80.4, 84.6, 117.2,
122.5, 126.3, 129.8, 130.0, 130.8, 135.4, 144.6. Anal. Calcd for
C17H21Br: C, 66.89; H, 6.93. Found: C, 66.68; H, 7.17. IR (film) cmꢀ1
2928, 670. Data are in accordance with previously reported results.12
1H NMR (CDCl3, 400 MHz)
(m, 4H), 2.23 (dt, J¼2.2, 6.9 Hz, 2H), 2.44 (t, J¼7.0 Hz, 2H), 3.62 (tt,
d
ppm 0.92 (t, J¼7.2 Hz, 3H),1.40–1.56

1764
M. Georgy et al. / Tetrahedron 65 (2009) 1758–1766
J¼2.2, 7.0 Hz, 1H), 3.79 (s, 3H), 5.02 (d, J¼10.2 Hz, 1H), 5.03 (d,
J¼17.1 Hz, 1H), 5.85 (tdd, J¼7, 10.4, 17.3 Hz, 1H), 6.85 (m, 2H), 7.27
1H), 5.86 (m, 1H), 7.23–7.37 (m, 5H); 13C NMR (CDCl3, 100 MHz)
ppm 31.8, 38.7, 69.7, 85.5, 116.4, 125.9, 126.51 (2C), 128.42 (2C),
134.27, 140.02. Data are in accordance with previously reported
results.36
d
(m, 2H); 13C NMR (CDCl3, 100 MHz)
d
ppm 13.6, 18.5, 21.9, 31.1, 37.1,
43.1, 55.2, 81.3, 83.5, 113.0, 116.5, 128.3, 134.2, 135.9, 158.5; HREIMS
m/z 242.1670, calcd for C17H22O 242.1671; IR (film) cmꢀ1 3075,
2957, 1640, 1610, 828.
4.2.18. (3,3-Dimethylhex-5-en-1-ynyl)benzene (27)7
Prepared with 1.5 equiv of allyltrimethylsilane and isolated as
a clear oil.
4.2.12. 4-(Dec-1-en-5-yn-4-yl)phenol (16)
Prepared with 3 equiv of allyltrimethylsilane and isolated as
a colorless oil.
1H NMR (CDCl3, 300 MHz)
d
ppm 1.31 (s, 6H), 2.29 (d, J¼7.2 Hz,
2H), 5.14 (d, J¼8.8 Hz, 1H), 5.14 (d, J¼16.8 Hz, 1H), 6.04 (m, 1H), 7.29
(m, 3H), 7.42 (m, 2H); 13C NMR (CDCl3, 75 MHz)
ppm 29.0, 31.5,
1H NMR (CDCl3, 400 MHz)
d
ppm 0.91 (t, J¼7.2 Hz, 3H), 1.37–1.54
d
(m, 4H), 2.22 (dt, J¼2.2, 6.9 Hz, 2H), 2.42 (t, J¼7.1 Hz, 2H), 3.60 (tt,
J¼2.2, 7.0 Hz, 1H), 4.66 (s, 3H), 5.01 (d, J¼10.2 Hz, 1H), 5.02 (d,
J¼16.32 Hz, 1H), 5.83 (tdd, J¼7, 10.4, 16.4 Hz, 1H), 6.77 (d, J¼8.51 Hz,
47.9, 80.7, 97.1, 117.5, 124.2, 127.5, 128.5, 131.8, 135.5. Data are in
accordance with previously reported results.7
2H), 7.24 (d, J¼8.5 Hz, 2H); 13C NMR (CDCl3, 100 MHz)
d
ppm 13.6,
4.2.19. (4-Methyloct-1-en-5-yn-4-yl)benzene (28)12
Prepared with 1.5 equiv of allyltrimethylsilane and isolated as
a clear oil.
18.4, 21.9, 31.1, 37.1, 43.1, 81.3, 83.5, 115.0, 116.6, 128.6, 134.4, 135.8,
154.0; HREIMS m/z 229.1591, calcd for C16H20O 229.1592; IR (film)
cmꢀ1 3321, 3055, 2929, 1638, 1613.
1H NMR (CDCl3, 300 MHz)
d
ppm 0.93 (t, J¼7 Hz, 3H), 1.40 (m,
4H), 1.54 (s, 3H), 1.55 (m, 2H), 2.27 (t, J¼6.9 Hz, 2H), 2.52 (m, 2H),
5.00 (d, J¼15.5 Hz, 1H), 5.01 (d, J¼12 Hz, 1H), 5.80 (m, 1H), 7.23 (m,
4.2.13. 1,4-Di(dec-1-en-5-yn-4-yl)benzene (20)
Prepared with 6 equiv of allyltrimethylsilane and isolated as
a colorless oil.
3H), 7.54 (d, J¼7.8 Hz, 2H); 13C NMR (CDCl3, 75 MHz)
d ppm 14.0,
18.8, 22.2, 28.8, 29.5, 29.7, 31.1, 40.0, 48.9, 84.0, 84.9, 117.2, 126.2,
128.0, 135.2, 146.0. Data are in accordance with previously reported
results.12
1H NMR (CDCl3, 400 MHz)
d
ppm 0.92 (t, J¼7.2 Hz, 6H),1.40–1.53
(m, 8H), 2.23 (dt, J¼2.0, 6.9 Hz, 4H), 2.44 (t, J¼6.9 Hz, 4H), 3.64 (tt,
J¼2.2, 7.1 Hz, 2H), 5.03 (d, J¼9.9 Hz, 2H), 5.04 (d, J¼18.5 Hz, 2H),
5.85 (tdd, J¼7, 10.1, 17.3 Hz, 2H), 7.29 (s, 4H); 13C NMR (CDCl3,
4.2.20. (3-(4-Methoxyphenyl)-3-phenylprop-1-ynyl)-
trimethylsilane (30)37
100 MHz)
d ppm 13.6 (2C), 18.5 (2C), 21.9 (2C), 31.1 (2C), 37.6 (2C),
43.0 (2C), 81.1 (2C), 83.6 (2C), 116.5 (2C), 127.4 (4C),135.8 (2C),140.3
(2C); HREIMS m/z 346.2659, calcd for C26H34 346.2661; IR (film)
cmꢀ1 3076, 2930, 1640, 728.
Prepared with 1.1 equiv of anisole and isolated as a clear oil.
1H NMR (CDCl3, 300 MHz)
d ppm 0.27 (s, 9H), 2.96 (s, 3H), 5.00
(s, 1H), 6.86 (d, J¼8.6 Hz, 2H), 7.20–7.33 (m, 5H), 7.38 (m, 2H); 13C
NMR (CDCl3, 75 MHz)
d ppm 0.1, 43.3, 55.3, 88.9, 107.1, 114.1, 126.7,
4.2.14. Oct-7-en-3-yne-1,5-diyldibenzene (22)
Prepared with 6 equiv of allyltrimethylsilane and isolated as
a colorless oil.
127.8, 128.5, 128.8, 133.8, 141.9, 158.5. Data are in accordance with
previously reported results.37
1H NMR (CDCl3, 400 MHz)
d
ppm 2.44 (t, J¼7.0 Hz, 2H), 2.54 (dt,
4.2.21. (3-(2,4-Dimethoxyphenyl)prop-1-yne-1,3-diyl)-
dibenzene (31)10
J¼2.2, 7.4 Hz, 2H), 2.85 (t, J¼7.4 Hz, 2H), 3.64 (tt, J¼2.2, 7.2 Hz, 1H),
5.01 (d, J¼11.2 Hz, 1H), 5.02 (d, J¼16 Hz, 1H), 5.86 (tdd, J¼7, 11,
Prepared with 5 equiv of 1,3-dimethoxybenzene and isolated as
a white solid.
16.5 Hz, 1H), 7.20–7.31 (m, 10H); 13C NMR (CDCl3, 100 MHz)
d ppm
21.0, 35.4, 37.9, 42.8, 81.9, 82.8, 116.6, 126.1, 126.5, 127.4 (3C), 128.2
(3C), 128.5 (2C), 135.7, 140.8, 141.8; HREIMS m/z 260.1561, calcd for
C20H20 260.1565; IR (film) cmꢀ1 3062, 2929, 1641, 1602, 739.
1H NMR (CDCl3, 300 MHz)
d ppm 3.82 (s, 3H), 3.83 (s, 3H),
5.63 (s, 1H), 6.48 (d, J¼2.4 Hz, 1H), 6.53 (dd, J¼2.4, 8.4 Hz, 1H),
7.22 (m, 1H), 7.31 (m, 5H), 7.49 (m, 4H), 7.52 (d, J¼8.3 Hz, 1H); 13C
NMR (CDCl3, 75 MHz)
d ppm 36.3, 55.6, 55.8, 83.6, 91.4, 98.8,
4.2.15. Trimethyl(3-phenylhex-5-en-1-ynyl)silane (23)7
Prepared with 1.5 equiv of allyltrimethylsilane and isolated as
a clear oil.
104.8, 123.1, 124.0, 126.6, 128.0, 128.4, 128.5, 129.7, 131.9, 142.3,
157.3, 160.1. Data are in accordance with previously reported
results.10
1H NMR (CDCl3, 300 MHz)
d
ppm 0.23 (s, 9H), 2.55 (t, J¼7.1 Hz,
2H), 3.72 (t, J¼7.1 Hz, 1H), 5.04 (d, J¼11 Hz, 1H), 5.07 (d, J¼15.5 Hz,
4.2.22. 2-(1,3-Diphenylprop-2-ynyl)furan (32)10
1H), 5.85 (m, 1H), 7.24 (m, 1H), 7.34 (m, 4H); 13C NMR (CDCl3,
Prepared with 1.5 equiv of furan and isolated as a yellow oil.
75 MHz)
d
ppm 0.2, 38.8, 42.7, 87.7, 107.5, 116.8, 126.6, 127.4, 128.2,
1H NMR (CDCl3, 300 MHz)
d
ppm 5.29 (s, 1H), 6.30 (d, J¼3.2 Hz,
135.1, 140.9. Data are in accordance with previously reported
results.7
1H), 6.34 (dd, J¼1.9, 3.2 Hz, 1H), 7.32 (m, 7H), 7.50 (m, 4H); 13C NMR
(CDCl3, 75 MHz)
d ppm 38.0, 84.1, 87.6, 106.8, 110.5, 123.3, 127.5,
128.0, 128.4, 128.8, 131.9, 139.0, 142.4, 153.9. Data are in accordance
4.2.16. Hex-5-en-1-yne-1,3-diyldibenzene (24)35
Prepared with 1.5 equiv of allyltrimethylsilane and isolated as
a clear oil.
with previously reported results.10
4.2.23. 3-Acetyl-4-phenyldecane-2,6-dione (34)
Prepared with 5 equiv of acetylacetone and isolated as a clear
oil.
1H NMR (CDCl3, 300 MHz)
d
ppm 2.62 (t, J¼7 Hz, 2H), 3.94 (t,
J¼7 Hz, 1H), 5.13 (m, 2H), 5.96 (ddt, J¼7, 10.1, 17.1 Hz, 1H), 7.30–7.49
(m, 10H); 13C NMR (CDCl3, 75 MHz)
ppm 38.6, 42.8, 83.8, 90.9,
d
1H NMR (CDCl3, 400 MHz)
d
ppm 0.79 (t, J¼7.3 Hz, 3H), 1.08–
117.1, 123.7, 125.9, 126.3, 126.8, 127.3, 127.6, 127.8, 131.7, 131.9, 135.5,
141.4. Data are in accordance with previously reported results.35
1.18 (m, 2H), 1.32–1.40 (m, 2H), 1.86 (s, 3H), 2.06–2.25 (m, 2H),
2.24 (s, 3H), 2.59 (dd, J¼4.3, 16.1 Hz, 1H), 2.74 (dd, J¼9.0,
16.1 Hz, 1H), 4.02 (ddd, J¼4.3, 9.0, 11.1 Hz, 1H), 4.21 (d,
J¼11.1 Hz, 1H), 7.17–7.28 (m, 5H); 13C NMR (CDCl3, 100 MHz)
4.2.17. Hex-5-en-1-yn-3-ylbenzene (26)36
Prepared with 1.5 equiv of allyltrimethylsilane and isolated as
a clear oil.
d
ppm 13.7, 22.0, 25.4, 29.7, 29.9, 40.8, 43.2, 46.7, 74.7, 127.2,
128.0 (2C), 128.8 (2C), 140.3, 203.3, 203.3, 208.7; HREIMS m/z
2889.1793, calcd for C18H24O3 289.1804; IR (film) cmꢀ1 2957,
1704, 1682, 701.
1H NMR (CDCl3, 400 MHz)
2H), 3.71 (t, J¼7.0 Hz,1H), 5.06 (d, J¼10.4 Hz,1H), 5.08 (d, J¼15.8 Hz,
d
ppm 2.30 (s, 1H), 2.52 (t, J¼7.1 Hz,

M. Georgy et al. / Tetrahedron 65 (2009) 1758–1766
1765
4.2.24. 1-(2-Methyl-5-pentyl-4-phenylfuran-3-yl)ethanone (35)
J¼3.9, 13.9 Hz, 1H), 4.23 (q, J¼7.1 Hz, 2H), 4.65 (br s, 1H), 5.21 (s,
1H), 5.35 (t, J¼7.7 Hz, 1H), 7.31–7.40 (m, 6H), 7.50–7.60 (m, 4H);
second diastereoisomer 1.27 (t, J¼7.3 Hz, 3H), 1.45 (s, 9H), 3.07
(dd, J¼7, 13.9 Hz, 1H), 3.31 (dd, J¼5.1, 14 Hz, 1H), 4.20 (q, J¼7.1 Hz,
2H), 4.60 (br s, 1H), 5.21 (s, 1H), 5.35 (t, J¼7.7 Hz, 1H), 7.31–7.40
Prepared with 5 equiv of acetylacetone and isolated as a clear
oil.
1H NMR (CDCl3, 400 MHz)
d
ppm 0.82 (t, J¼7.1 Hz, 3H), 1.19–1.25
(m, 4H), 1.56 (m, 2H), 1.90 (s, 3H), 2.44 (t, J¼7.7 Hz, 2H), 2.54 (s, 3H),
7.22–7.39 (m, 5H); 13C NMR (CDCl3, 100 MHz)
ppm 13.9, 14.3, 25.7,
d
(m, 6H), 7.50–7.60 (m, 4H); 13C NMR (CDCl3, 75 MHz)
d ppm first
28.1, 30.7, 30.7, 31.1, 120.5, 122.9, 127.3, 128.3 (2C), 129.9 (2C), 138.8,
151.1, 156.2, 196.2; HREIMS m/z 271.1698, calcd for C18H22O2
271.1699; IR (film) cmꢀ1 2955, 1670, 1612, 1557.
diastereoisomer 14.3, 28.5, 34.8, 39.6, 53.1, 61.9, 80.2, 86.7, 86.9,
122.7, 128.1, 128.1, 128.4, 128.5, 128.8, 131.9, 137.8, 155.3, 171.1;
second diastereoisomer 14.3, 28.5, 34.5, 39.9, 53.2, 61.9, 80.2,
86.5, 86.6, 122.8, 128.1, 128.2, 128.4, 128.6, 128.8, 131.9, 137.9,
155.4, 171.2.
4.2.25. (1-Butoxypent-2-ynyl)benzene (36)12
Prepared with 1.5 equiv of 1-butanol and isolated as a clear oil.
1H NMR (CDCl3, 300 MHz)
d
ppm 0.91 (t, J¼7 Hz, 3H), 0.92 (t,
4.2.31. (1-Phenyloct-2-ynyl)benzenesulfonamide (42)40
Prepared with 1.2 equiv of benzenesulfonamide and isolated as
a clear oil.
J¼7.3 Hz, 3H), 1.37 (m, 6H), 1.59 (m, 4H), 2.28 (td, J¼2.2, 7 Hz, 2H),
3.48 (dt, J¼6.7, 9 Hz, 1H), 3.64 (dt, J¼6.7, 8.9 Hz, 1H), 5.15 (s, 1H),
7.34 (m, 3H), 7.52 (d, J¼7.2 Hz, 2H); 13C NMR (CDCl3, 75 MHz)
d
ppm
1H NMR (CDCl3, 400 MHz)
d
ppm 0.88 (t, J¼7.3 Hz, 3H), 1.19–
14.0, 14.1, 19.0, 19.5, 22.3, 28.5, 31.2, 31.9, 68.0, 71.8, 78.3, 88.3, 127.5,
128.2, 128.5, 139.8. Data are in accordance with previously reported
results.12
1.34 (m, 6H), 1.94–1.98 (m, 2H), 4.78 (d, J¼8.8 Hz, 1H), 5.30 (d,
J¼8.8 Hz, 1H), 7.27–7.33 (m, 5H), 7.46–7.48 (m, 3H), 7.77 (d,
J¼8.3 Hz, 2H); 13C NMR (CDCl3, 100 MHz)
d ppm 13.9, 18.5, 22.1,
27.9, 31.0, 49.4, 76.6, 87.5, 127.2, 127.5, 128.1, 128.5, 129.3, 137.6,
138.2, 143.2. Data are in accordance with previously reported
results.40
4.2.26. (3-(But-3-enyloxy)-3-phenylprop-1-ynyl)trimethyl-
silane (37)9
Prepared with 1.5 equiv of 3-buten-1-ol and isolated as a clear
oil.
4.2.32. 3-Methyl-1-phenylbut-2-en-1-one (44)39
1H NMR (CDCl3, 300 MHz)
d
ppm 0.22 (s, 9H), 2.40 (q, J¼6.8 Hz,
Prepared with 1.5 equiv of ethanol and isolated as a clear oil.
2H), 3.57 (dt, J¼7.1, 8.5 Hz, 1H), 3.71 (dt, J¼6.9, 8.8 Hz, 1H), 5.05 (d,
J¼10.2 Hz, 1H), 5.12 (d, J¼17.3 Hz, 1H), 5.21 (s, 1H), 5.85 (ddt, J¼6.7,
10.3,17 Hz,1H), 7.36 (m, 3H), 7.52 (d, J¼7.6 Hz, 2H); 13C NMR (CDCl3,
1H NMR (CDCl3, 300 MHz)
d
ppm 2.03 (s, 3H), 2.22 (s, 3H), 6.75
(s, 1H), 7.43 (t, J¼7.2 Hz, 2H), 7.52 (t, J¼7.2 Hz, 1H), 7.93 (d, J¼7.2 Hz,
2H); 13C NMR (CDCl3, 75 MHz)
ppm 20.8, 27.6, 120.7, 127.7, 128.0,
d
75 MHz)
d
ppm 0.06, 34.2, 67.6, 72.0, 92.7, 103.3, 116.5, 127.6, 128.4,
131.8, 138.8, 156.4, 190.7. Data are in accordance with previously
reported results.39
128.5, 135.4, 138.6. Data are in accordance with previously reported
results.9
4.2.33. (E)-1-Phenyloct-1-en-3-one (45)41
4.2.27. (3-(3-Chloropropoxy)-3-methylbut-1-ynyl)benzene (38)9
Prepared with 1.5 equiv of 3-chloropropan-1-ol and isolated as
a clear oil.
Prepared with 1.5 equiv of ethanol and isolated as a clear oil.
1H NMR (CDCl3, 300 MHz)
d
ppm 0.93 (t, J¼7 Hz, 3H), 1.37 (m,
4H), 1.70 (m, 2H), 2.67 (t, J¼7 Hz, 2H), 6.70 (d, J¼16 Hz, 1H), 7.30–
1H NMR (CDCl3, 300 MHz)
d
ppm 1.56 (s, 6H), 2.07 (m, 2H), 3.70
(t, J¼6.4 Hz, 2H), 3.78 (t, J¼5.8 Hz, 2H), 7.32 (m, 3H), 7.44 (m, 2H);
13C NMR (CDCl3, 75 MHz)
ppm 28.6, 33.3, 42.2, 60.6, 70.5, 84.0,
7.40 (m, 3H), 7.53 (m, 2H), 7.56 (d, J¼16 Hz, 1H); 13C NMR (CDCl3,
75 MHz)
d ppm 13.9, 22.5, 24.1, 29.7, 40.9, 126.7, 128.2 (2C), 128.9
d
(2C), 130.4, 134.6, 142.3, 200.7. Data are in accordance with pre-
91.6, 122.9, 128.2, 128.3, 131.7. Data are in accordance with pre-
viously reported results.9
viously reported results.41
4.2.34. (1-Ethoxyoct-2-ynyl)benzene (46)12
4.2.28. (1,3-Diphenylprop-2-ynyl)(phenyl)sulfane (39)38
Prepared with 1.5 equiv of ethanol and isolated as a clear oil.
Prepared with 1.5 equiv of thiophenol and isolated as a clear oil.
1H NMR (CDCl3, 300 MHz)
d
ppm 0.91 (t, J¼7 Hz, 3H), 1.2 (t,
1H NMR (CDCl3, 300 MHz)
d
ppm 5.24 (s, 1H), 7.32 (m, 9H), 7.40
J¼7 Hz, 3H), 1.37 (m, 4H), 1.57 (m, 2H), 2.29 (dt, J¼1.9, 7 Hz, 2H), 3.5
(m, 2H), 7.48 (m, 4H); 13C NMR (CDCl3, 75 MHz)
d
ppm 44.4, 87.0,
(m, 1H), 3.70 (m, 1H), 5.1 (s, 1H), 7.30–7.40 (m, 3H), 7.53 (m, 2H); 13C
87.5, 123.1, 128.0, 128.2, 128.4, 128.4, 128.6, 128.6, 128.8, 131.8, 133.5,
134.6, 138.2. Data are in accordance with previously reported
results.38
NMR (CDCl3, 75 MHz) d ppm 14.1, 15.2, 18.8, 22.2, 28.3, 31.1, 63.5,
71.6, 78.2, 88.2, 127.4 (2C), 128.1, 128.4 (2C), 139.6. Data are in ac-
cordance with previously reported results.12
4.2.29. Ethyl 2-(1-phenylpent-2-ynylthio)acetate (40)12
Prepared with 1.5 equiv of ethylmercaptoacetate and isolated as
a clear oil.
4.2.35. 1,3-Diphenylpropyne (47)42
Prepared with 1.2 equiv of triethylsilane and isolated as a clear
oil.
1H NMR (CDCl3, 300 MHz)
d
ppm 0.92 (t, J¼7 Hz, 3H), 1.24–1.44
1H NMR (CDCl3, 400 MHz)
d
ppm 3.83 (s, 2H), 7.23–7.46 (m,
(m, 4H), 1.30 (t, J¼7 Hz, 3H), 1.60 (m, 2H), 2.30 (td, J¼2.2, 7 Hz, 2H),
3.23 (d, J¼15 Hz, 1H), 3.50 (d, J¼15 Hz,1H), 4.19 (q, J¼7 Hz, 2H), 5.01
(s, 1H), 7.30 (d, J¼7.3 Hz, 1H), 7.52 (t, J¼7.3 Hz, 2H), 7.53 (d, J¼7.3 Hz,
10H); 13C NMR (CDCl3,100 MHz)
d ppm 25.7, 82.6, 84.5,123.6,126.6,
127.8 (2C), 127.9 (2C), 128.2, 128.5 (2C), 131.6 (2C), 136.7. Data are in
accordance with previously reported results.42
2H); 13C NMR (CDCl3, 75 MHz)
d ppm 14.1,14.3,19.0, 22.3, 28.6, 31.2,
33.8, 39.7, 61.5, 77.0, 87.6,127.5,128.2,128.7,138.2, 170.4. Data are in
4.2.36. Hept-2-ynylbenzene (48)
accordance with previously reported results.12
Prepared with 1.2 equiv of triethylsilane and isolated as a clear
oil.
4.2.30. (2R)-Ethyl 2-(tert-butoxycarbonylamino)-3-(1,3-
1H NMR (CDCl3, 400 MHz)
d
ppm 0.84 (t, J¼7.2 Hz, 3H),1.30–1.47
(m, 4H), 2.12–2.16 (m, 2H), 3.49 (m, 2H), 7.11–7.27 (m, 5H); 13C NMR
(CDCl3, 100 MHz) ppm 13.6, 18.5, 22.0, 25.1, 31.1, 77.4, 82.6, 126.3,
diphenylprop-2-ynylthio)propanoate (41)12
Prepared with 1.5 equiv of Boc(
mixture of two diastereoisomers (clear oil).
1H NMR (CDCl3, 300 MHz)
ppm first diastereoisomer 1.25 (t,
J¼7.3 Hz, 3H), 1.46 (s, 9H), 2.93 (dd, J¼7, 13.9 Hz, 1H), 3.43 (dd,
L)-Cys-OEt and isolated as a 1:1
d
127.8 (2C), 128.4 (2C), 137.6; HREIMS m/z 172.1253, calcd for C13H16
172.1252; IR (film) cmꢀ1 3086, 3064, 3029, 2931, 2872, 2204, 1707,
1605.
d

1766
M. Georgy et al. / Tetrahedron 65 (2009) 1758–1766
M. Angew. Chem., Int. Ed. 2006, 45, 4835–4839; (c) Inada, Y.; Nishibayashi, Y.;
4.2.37. 1-(Hept-2-ynyl)-2-methylbenzene (49)
Uemura, S. Angew. Chem., Int. Ed. 2005, 44, 7715–7717.
Prepared with 1.2 equiv of triethylsilane and isolated as a clear
oil.
6. (a) Bustelo, E.; Dixneuf, P. H. Adv. Synth. Catal. 2007, 349, 933–942; (b) Bustelo,
E.; Dixneuf, P. H. Adv. Synth. Catal. 2005, 347, 393–397; (c) Cadierno, V.; Diez, J.;
Garcia-Garrido, S. E.; Gimeno, J. Chem. Commun. 2004, 2716–2717.
7. Luzung, M. R.; Toste, F. D. J. Am. Chem. Soc. 2003, 125, 15760–15761.
8. Ohri, R. V.; Radosevich, A. T.; Hrovat, K. J.; Musich, C.; Huang, D.; Holman, T. R.;
Toste, F. D. Org. Lett. 2005, 7, 2501–2504.
1H NMR (CDCl3, 400 MHz)
d
ppm 0.92 (t, 3H, J¼7.2 Hz),1.38–1.55
(m, 4H), 2.22 (tt, J¼2.0, 7.1 Hz, 2H), 2.31 (s, 3H), 3.50 (t, J¼2.3 Hz,
2H), 7.15–7.21 (m, 3H), 7.45 (d, J¼6.9 Hz, 1H); 13C NMR (CDCl3,
9. Sherry, B. D.; Radosevich, A. T.; Toste, F. D. J. Am. Chem. Soc. 2003, 125,
6076–6077.
100 MHz)
d ppm 13.6, 18.5, 19.2, 22.0, 23.3, 31.1, 77.0, 82.8, 126.0,
126.6, 128.1, 130.0, 135.8, 135.9; HREIMS m/z 186.1404, calcd for
10. Kennedy-Smith, J. J.; Young, L. A.; Toste, F. D. Org. Lett. 2004, 6, 1325–1327.
11. Kuninobu, Y.; Ishii, E.; Takai, K. Angew. Chem., Int. Ed. 2007, 46, 3296–
3299.
C14H18 186.1409; IR (film) cmꢀ1 2960, 2931, 2873, 2199, 1707, 1602.
4.2.38. N-Tosyl-1,10-diphenylmethylamine (51)31
Prepared with 3 equiv of tosylamine and isolated as a white
solid.
12. For a preliminary communication, see: Georgy, M.; Boucard, V.; Campagne, J. M.
J. Am. Chem. Soc. 2005, 127, 14180–14181.
13. Liu, J.; Muth, E.; Floerke, U.; Henkel, G.; Merz, K.; Sauvageau, J.; Schwake, E.;
Dyker, G. Adv. Synth. Catal. 2006, 348, 456–462.
14. (a) Sanz, R.; Martinez, A.; Alvarez-Gutierrez, J. M.; Rodriguez, F. Eur. J. Org. Chem.
2006, 1383–1386; (b) Zhan, Z.-P.; Yu, J.-L.; Liu, H.-J.; Cui, Y.-Y.; Yang, R.-F.; Yang,
W.-Z.; Li, J.-P. J. Org. Chem. 2006, 71, 8298–8301.
15. Sanz, R.; Miguel, D.; Martinez, A.; Alvarez-Gutierrez, J. M.; Rodriguez, F. Org.
Lett. 2007, 9, 727–730.
1H NMR (CDCl3, 300 MHz)
d
ppm 2.38 (s, 3H), 5.24 (d, J¼7.1 Hz,
1H), 5.58 (d, J¼7.1 Hz, 1H), 7.09–7.23 (m, 12H), 7.57 (d, J¼8.3 Hz,
2H); 13C NMR (CDCl3, 75 MHz)
ppm 21.4, 61.3, 127.2 (2C), 127.3
d
(4C), 127.5 (2C), 128.5 (4C), 129.3 (2C), 137.3, 140.5 (2C), 143.2. Data
are in accordance with previously reported results.31
16. Sanz, R.; Martinez, A.; Miguel, D.; Alvarez-Gutierrez, J. M.; Rodriguez, F.
Synthesis 2007, 3252–3256.
17. Huang, W.; Shen, Q.; Wang, J.; Zhou, X. J. Org. Chem. 2008, 73, 1586–1589.
18. (a) Yadav, J. S.; Reddy, B. V. S.; Rao, T. S.; Rao, K. V. R. Tetrahedron Lett. 2008, 49,
614–618; (b) Hui, H.-h.; Zhao, Q.; Yang, M.-y.; She, D.-b.; Chen, M.; Huang, G.-s.
Synthesis 2008, 191–196; (c) Lee, K.; Lee, P. H. Org. Lett. 2008, 10, 2441–2444; (d)
Yadav, J. S.; Reddy, B. V. S.; Rao, K. V. R.; Kumar, G. G. K. S. N. Synthesis 2007,
3205–3210; (e) Zhan, Z.-P.; Yang, W.-Z.; Yang, R.-F.; Yu, J.-L.; Li, J.-P.; Liu, H.-J.
Chem. Commun. 2006, 3352–3354; (f) Qin, H.; Yamagiwa, N.; Matsunaga, S.;
Shibasaki, M. Angew. Chem., Int. Ed. 2007, 46, 409–413; (g) Yadav, J. S.; Reddy, B.
V. S.; Rao, K. V. R.; Kumar, G. G. K. S. N. Tetrahedron Lett. 2007, 48, 5573–5576;
(h) Huang, W.; Wang, J.; Shen, Q.; Zhou, X. Tetrahedron 2007, 63, 11636–11643;
(i) Srihari, P.; Reddy, J. S. S.; Bhunia, D. C.; Mandal, S. S.; Yadav, J. S. Synth.
Commun. 2008, 38, 1448–1455; (j) Srihari, P.; Bhunia, D. C.; Sreedhar, P.;
Mandal, S. S.; Reddy, J. S. S.; Yadav, J. S. Tetrahedron Lett. 2007, 48, 8120–8124.
19. Kabalka, G. W.; Yao, M.-L. Curr. Org. Synth. 2008, 5, 28–32.
20. (a) Kabalka, G. W.; Yao, M.-L.; Borella, S. J. Am. Chem. Soc. 2006, 128, 11320–
11321; (b) Kabalka, G. W.; Wu, Z.; Ju, Y. Org. Lett. 2004, 6, 3929–3931.
21. Georgy, M.; Lesot, P.; Campagne, J.-M. J. Org. Chem. 2007, 72, 3543–3549 and
refs. cited.
4.2.39. N-Tosyl-1-phenylethylamine (53)31
Prepared with 3 equiv of tosylamine and isolated as a white
solid.
1H NMR (CDCl3, 300 MHz)
d
ppm 1.42 (d, J¼6.9 Hz, 3H), 2.39 (s,
3H), 4.47 (quint, J¼6.9 Hz, 1H), 5.23 (d, J¼7.1 Hz, 1H), 7.10–7.13 (m,
2H), 7.16–7.19 (m, 5H), 7.63 (d, J¼8.1 Hz, 2H); 13C NMR (CDCl3,
75 MHz)
d ppm 21.4, 23.5, 53.6, 126.1 (2C), 127.0 (2C), 127.3, 128.4
(2C), 129.4 (2C), 137.6, 142.0, 143.0. Data are in accordance with
previously reported results.31
4.2.40. N-(1,3-Diphenyl-2(E)-propenyl)-4-methyl-
benzenesulfonamide (55)43
Prepared with 1.1 equiv of tosylamine and isolated as a white
solid.
22. Lu, G.; Li, Y.-M.; Li, X.-S.; Chan, A. S. C. Coord. Chem. Rev. 2005, 249, 1736–1744.
23. Fukuda, Y.; Utimoto, K. J. Org. Chem. 1991, 56, 3729–3731.
24. Evans, D. A.; Chapman, K. T.; Carreira, E. M. J. Am. Chem. Soc. 1988, 110,
3560–3578.
25. Luzung, M. R.; Markham, J. P.; Toste, F. D. J. Am. Chem. Soc. 2004, 126,
10858–10859.
1H NMR (CDCl3, 400 MHz)
d
ppm 2.16 (s, 3H), 4.97 (dd, J¼6.7,
6.9 Hz, 1H), 5.38 (d, J¼7.5 Hz, 1H), 5.93 (dd, J¼6.8, 15.8 Hz, 1H), 6.19
(d, J¼15.7 Hz,1H), 6.96–7.13 (m,12H), 7.52 (m, 2H); 13C NMR (CDCl3,
100 MHz)
d ppm 21.3, 59.7, 126.5 (2C), 127.0 (2C), 127.2 (2C), 127.7,
26. Michelet, V.; Toullec, P. Y.; Geneˆt, J.-P. Angew. Chem., Int. Ed. 2008, 47,
4268–4315.
127.8, 128.1, 128.4 (2C), 128.6 (2C), 129.4 (2C), 131.9, 136.0, 137.6,
139.6, 143.2. Data are in accordance with previously reported
results.43
27. Debleds, O.; Campagne, J.-M. J. Am. Chem. Soc. 2008, 130,
1562–1563.
28. The low yield observed in the formation of 26 is mainly due to the instability of
the compound, which rapidly decomposes at rt.
29. For recent accounts dealing with gold-catalyzed Meyer–Schuster rearrange-
ment, see: (a) Engel, D. A.; Dudley, G. B. Org. Lett. 2006, 8, 4027–4029; (b) Egi,
M.; Yamaguchi, Y.; Fujiwara, N.; Akai, S. Org. Lett. 2008, 10, 1867–1870; (c)
Lopez, S. S.; Engel, D. A.; Dudley, G. B. Synlett 2007, 949–953; (d) Marion, N.;
Carlqvist, P.; Maseras, F.; Nolan, S. P. Chem.dEur. J. 2007, 13, 6437–6451.
30. Midland, M.; Tramontano, A.; Kazubski, A.; Graham, R. S.; Tsai, D. J. S.; Cardin,
D. B. Tetrahedron 1984, 40, 1371–1380.
Acknowledgements
We are grateful to the CNRS for financial support (ATIPE jeune
´
equipe), the Institut de Chime des Substances Naturelles (Gif-sur-
Yvette) and MENRT for Ph.D. grants (OD, CDZ, MG). We also thank
Prof. Damien Prim for helpful discussions.
31. Terrasson, V.; Marque, S.; Georgy, M.; Campagne, J.-M.; Prim, D. Adv. Synth.
Catal. 2006, 348, 2063–2067.
32. For related Au-catalyzed substitutions on benzylic positions, see: (a) Ref. 13; (b)
Mertins, K.; Iovel, I.; Kischel, J.; Zapf, A.; Beller, M. Adv. Synth. Catal. 2006, 348,
691–695.
References and notes
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