Gold-catalyzed efficient preparation of linear α-haloenones from propargylic acetates

Article abstract of DOI:10.1016/j.tet.2008.11.107

Versatile linear α-iodo- and α-bromoenones are prepared efficiently from readily accessible propargylic acetates using 2 mol % of Au(PPh₃)NTf₂. This reaction is easy to execute and has broad substrate scope. Good to excellent Z-selectivities are observed in the cases of propargylic acetates derived from aliphatic aldehydes.

Full text of DOI:10.1016/j.tet.2008.11.107

Tetrahedron 65 (2009) 1846–1855
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Gold-catalyzed efficient preparation of linear
from propargylic acetates
a-haloenones
*
Meng Yu, Guozhu Zhang, Liming Zhang
Department of Chemistry/MS 216, University of Nevada, Reno, 1664 North Virginia Street, Reno, NV 89557, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 June 2008
Received in revised form 23 November 2008
Accepted 24 November 2008
Available online 24 December 2008
Versatile linear a-iodo- and a-bromoenones are prepared efficiently from readily accessible propargylic
acetates using 2 mol % of Au(PPh3)NTf2. This reaction is easy to execute and has broad substrate scope.
Good to excellent Z-selectivities are observed in the cases of propargylic acetates derived from aliphatic
aldehydes.
Ó 2008 Published by Elsevier Ltd.
1. Introduction
Propargylic acetates are readily available starting materials and
can be easily prepared from aldehydes/ketones, terminal alkynes,
a
-Haloenones, especially
a
-iodoenones, are important synthetic
and acetic anhydride. They are versatile substrates for Au catalysis9
and can undergo either 1,2-acetoxyl migration10 or 3,3-rearrang-
ment.11,12 We originated and have since continued studies on
Au-catalyzed tandem reactions of propargylic esters involving 3,3-
rearrangement. In our design, the in situ generated carboxyallenes
could be further activated by the very same Au catalyst to form Au-
containing oxocarbenium A (Scheme 1). Intermediate A contains
various functionalities including oxocarbenium, C–C double bond,
activated acyl group, and potentially nucleophilic Au–C(sp2) bond;
moreover, due to the ease of substrate preparation, various
functional groups can be easily incorporated into oxocarbenium
intermediates and can undergo transition metal-catalyzed cross-
coupling reactions following Negishi’s protocols,1 readily installing
various substituents including alkyl, alkenyl, alkynyl, and aryl
groups at the enone
A range of methods for the synthesis of
been developed. For -bromoenones, brominations of enones
using commercially available or in situ generated bromine are the
most studied and straightforward approach2 although the strong
reactivity of Br2 prevents the inclusion of delicate functional
a-position.
a
-haloenones have
a
groups.
a-Iodoenones are much better substrates for transition
metal-catalyzed cross-coupling reactions,1 and their synthesis can
be achieved from enones using a combination of I2 and a nucle-
ophilic base (e.g., pyridine,3 DMAP,4 and quinuclidine4). However,
this Michael addition-based method is limited with linear enone
substrates.5 Although iodination of C–Si6 bonds with ICl or C–Sn7
bonds with I2 can afford linear a-iodoenones, the need of more
functionalized starting materials can be undesirable. McNelis
reported that propargylic alcohols could be converted directly into
R3
R3
R3
O
O
Au catalyst
O
O
O
O
R1
R1
R1
R2
R2
R2
R3
[Au]
[Au]
O
O
linear
amount of hydroxy(tosyloxy)iodobenzene;8 unfortunately, this
potentially versatile method for -iodoenone synthesis is limited
a-iodoenones using NIS (N-iodosuccinimide) and a catalytic
O
O
R3
various
[Au]
R1
a
functional
product
R1
•
[Au]
R2
R2
to secondary alkynols; moreover, its scope was not well defined as
only a few special examples of this chemistry were reported.
We concluded that an efficient and general preparative method
X
A
for linear
a-haloenones is still much needed. Herein, we give
O
O
a full account of our effort in addressing this need using Au
catalysis.
O
X
R3
hydrolysis
X
R2
R2
R1
R1
* Corresponding author. Tel.: þ1 775 784 6688; fax: þ1 775 784 6804.
E-mail address: lzhang@unr.edu (L. Zhang).
Scheme 1. Au-catalyzed tandem reactions of propargylic esters and the design for
-haloenone formation.
a
0040-4020/$ – see front matter Ó 2008 Published by Elsevier Ltd.
doi:10.1016/j.tet.2008.11.107

M. Yu et al. / Tetrahedron 65 (2009) 1846–1855
1847
A (i.e., in R1, R2, and R3). As a result, A is expected to have rich
chemistry. Indeed, based on this design, we have developed several
useful methods for efficient synthesis of highly functionalized 2,3-
a-iodoenone 2 was improved to 95%, and the stereoselectivity (Z/
E¼45:1) remained high. Although previous studies6,7 showed that
the double bond of
a-iodoenones could isomerize under acidic
indoline-fused cyclobutanes,11 cyclopentenones,13a
a
-alkylidene-
b
-
conditions, 1H NMR experiments showed that under the optimized
reaction conditions (i.e., entry 7) the Z/E ratio of 2 was constant
throughout the reaction and did not noticeably change at 0 ꢀC after
extended time. Other Au catalysts (e.g., entries 8–10) and PtCl2
(entry 11) gave less desirable results, and no reaction was observed
with NIS alone (entry 12).
diketones,13b alkenyl enol esters/carbonates,13c and enones.13d,14
Several other research groups have also developed efficient syn-
thetic methods sharing the design.15 A notable observation in some
of these studies is that the Au–C(sp2) bond in A can react with
intramolecular electrophiles16,17 including iminiums11 and acti-
vated acyl groups.13b We surmise that this Au–C(sp2) bond could
react with electrophilic halogens intermolecularly, leading to effi-
With the optimized reaction conditions in hand, we first studied
propargylic acetates derived from various aldehydes, and the re-
sults are summarized in Table 2. For all the substrates studied, good
cient formation of a
-haloenones upon hydrolysis (Scheme 1).18 In
fact, iodinations of Au–C(sp2) bonds with NIS had been realized in
isolated examples.19
to excellent yields of a-iodoenones with b-monosubstitution were
obtained. When R1 and R2 were both alkyl groups, excellent stereo-
selectivities favoring the Z-isomer were observed (entries 1–3, 8,
and 9). In the case of 3c, the sterically demanding cyclohexyl group
at the propargylic position slowed the reaction, and the addition of
10 mol % of AgNTf2 helped to complete the reaction in 3 h (entry 3).
The role of AgNTf2 was likely to scavenge Iꢁ and thus prevent
Au(PPh3)NTf2 from being deactivated by the halide.21 Notably, in
the cases of aryl-containing substrates 3d–g, the Z/E selectivities
were marginal (entries 4–7), and in entry 5 E-4e was the major
isomer. Aryl groups of different electronic natures underwent this
reaction smoothly, affording 4f and 4g in 84% and 96% yields, re-
spectively. Particularly noteworthy is that no iodination of the
anisole ring in 4f was observed. To our surprise, ester 3h with a 2-
acetoxyethyl at the propargylic position underwent concurrent
2. Results and discussion
We chose oct-3-yn-2-yl acetate (1) as substrate and NIS18 as the
‘Iþ’ source to study the reaction (Table 1). Stable Au(PPh3)NTf2 was
first used for its ease of preparation and handling.20 To our delight,
the desired reaction did happen with 2 mol % of the catalyst, and a-
iodoenone 2 was formed in anhydrous acetone in 95% yield albeit
without much Z/E selectivity (entry 1).
To improve the stereoselectivity, we examined different sol-
vents (entries 2 and 3). However, the improvement was moderate
and, moreover, at the expense of the reaction yield. After some
experimentation, we found that a small amount of water in acetone
dramatically enhanced the Z/E selectivity, and only Z-2 was ob-
served when acetone/H2O (40:1) was used as solvent (entry 4). To
our delight, the low yield could be overcome by decreasing the
amount of H2O. Hence, 61% and 80% yields of 2 were obtained when
the ratios of acetone/H2O were 200:1 (entry 5) and 400:1 (entry 6),
respectively; importantly, the excellent Z/E selectivity (>99:1)
remained unchanged. Finally, when the ratio of H2O and acetone
is 1:800 (about 1.4 equiv of H2O to 1, entry 7), the yield of
HOAc elimination, yielding Z-
8). In contrast, ester 3i with a longer carbon tether expectedly
yielded -iodoenone 4i in an excellent yield. Interestingly, when
a-iododienone 4h in 80% yield (entry
a
the acetyl groups of 4h and 4i were replaced with TBS groups, the
corresponding substrates reacted to give complicated mixtures. 1H
NMRs indicated that desilylation happened during reaction. Al-
though the reaction conditions are normally considered mild,
Au(PPh3)NTf2 is acidic enough to promote facile desilylation and
HOAc elimination (entry 8).
The scope of this
a-iodoenone formation can be readily ex-
Table 1
tended to propargylic acetates derived from ketones. As shown in
Table 3, under the same reaction conditions, acetates prepared
from linear ketones such as acetone (i.e., 5a) and 3-methylbutan-2-
one (i.e., 5e) underwent smooth Au-catalyzed reactions, affording
Gold-catalyzed reactions of propargylic acetate 1 with NIS to form
a
-iodoenone 2
OAc
O
catalyst, NIS (1.2 eq)
solvent, 0 °C, 2 h
Me
Me
Me
Me
b,b-disubstituted a-iodoenones in excellent yields (entries 1 and 5).
I
In the latter case, the diastereoselectivity was expectedly low.22
Similarly, substrates derived from cyclic ketones including cyclo-
pentanone (entry 2), cyclohexanone (entries 3, 6, and 7), and
cycloheptanone (entry 4) reacted efficiently, and the corresponding
1
2
Entrya Catalyst
Solvent
Yieldb [%] Z/Ec
1
2
3
4
5
6
7
8
2 mol % Au(PPh3)NTf2
2 mol % Au(PPh3)NTf2
2 mol % Au(PPh3)NTf2
2 mol % Au(PPh3)NTf2
2 mol % Au(PPh3)NTf2
2 mol % Au(PPh3)NTf2
2 mol % Au(PPh3)NTf2
2 mol % Au(III)g
Anhyd. acetone
Wet CH2Cl2
95
85
78
35e
61
80
95f
95
40j
6k
3:2
6:1
3:1
>99:1
>99:1
>99:1
45:1
6:1
a
-iodoenones were all isolated in excellent yields. In addition, the
d
MeNO2
alkyne terminus allowed various substituents including primary
(entries 1–5) and secondary (entry 6) alkyl groups as well as phenyl
group (entry 7). Remarkably, under this reaction conditions, no
enynes13d formed via elimination of HOAc were observed, sug-
gesting that Au(PPh3)NTf2 activates the C–C triple bond selectively.
Acetone/H2O (40:1)
Acetone/H2O (200:1)
Acetone/H2O (400:1)
Acetone/H2O (800:1)
ClCH2CH2Clh
9
2 mol % Au(I)i
Acetone/2O (800:1)
>99:1
d
10
11
12
2 mol % [(PhP3Au)3O]þNTf2ꢁ Acetone/H2O (800:1)
Although a-bromoenones are less desirable than a-iodoenones
for cross-coupling reactions,1 they are useful in various synthetic
transformations, including exchanging the Br with a CF3 group,23
Stille coupling,24 and synthesizing allenes via 2-bromoallylic alco-
2 mol % PtCl2
No catalyst
Toluenel
Acetone/H2O (800:1)
12.5
0m
>99:1
d
a
Reaction concentration is 0.05 M.
hols.25 To our delight, the protocol for
a-iodoenone formation can
b
c
d
e
f
Estimated by 1H NMR using diethyl phthalate as internal reference.
The geometries of enone 2 were determined by NOESY1D experiments.
Regular, without drying.
Acetate 1 (17%) was left unreacted.
Isolated yield (89%).
Dichloro(2-pyridinecarboxylato)gold(III).
Heating at 80 ꢀC for 0.5 h.
(2-Biphenyl)Cy2PAuNTf2.
be readily applied for a-bromoenone synthesis. In this case, NBS
was used as the ‘Brþ’ source. As shown in Table 4, propargylic ac-
etates derived from acetaldehyde (e.g., entry 1) and benzaldehyde
g
h
i
(e.g., entry 5) served as excellent substrates, affording
enones 8a and 8e, respectively, in excellent yields. Moreover, the
E/Z selectivities paralleled to those observed with -iodoenones.
Hence, Z-8a with alkyl substituents was almost exclusively formed,
while -bromoenone 8e with a -phenyl group was isolated as
a mixture with the E-isomer slightly favored. Propargylic acetates
a-bromo-
a
j
Starting material (47%) left after 2 h.
Mostly starting material left after 4.5 h.
Heating at 80 ꢀC for 2 h.
k
l
a
b
m
No reaction.

1848
M. Yu et al. / Tetrahedron 65 (2009) 1846–1855
Table 2
Formation of b-monosubstituted a-iodoenones
O
OAc
Au(PPh3)NTf2 (2 mol %), NIS (1.2 eq)
acetone:H2O = 800:1, 0 °C, 2 h
R1
R2
R1
R2
I
3
4
Entrya
Propargylic acetate 3
OAc
a
-Iodoenone 4
Z/E
Yieldb [%]
O
Me
1
3a
3b
3c
3d
4a
12:1
82
Me
I
OAc
O
O
Me
Me
Me
2
3
4
4b
4c
4d
10:1
19:1
1.2:1
94
91c
75d
3
3
Me
Me
3
I
3
OAc
Me
3
I
3
OAc
O
Me
Me
I
OAc
O
5
6
7
8
3e
3f
4e
4f
1:2
1:1
97e
84
I
OAc
O
Me
3
Me
I
3
MeO
MeO
OAc
O
Me
3g
3h
4g
4h
5:1
96f
80g
3
Me
I
3
F3C
F3C
OAc
O
Me
3
Z only
AcO
Me
I
3
OAc
O
AcO
Me
3
AcO
9
3i
4i
>50:1
83
Me
I
3
a
Substrate concentration is 0.05 M.
Isolated yield.
AgNTf2 (10 mol %) was added, and the reaction time was 3 h.
The reaction took 3 h.
The reaction finished in 0.5 h.
AgNTf2 (10 mol %) was added.
b
c
d
e
f
g
Elimination of acetic acid happened during the reaction.
derived from ketones reacted smoothly as well, yielding
moenones 8b–8d all in close to quantitative yields.
a
-bro-
group in the final product. The resulting intermediate, carbo-
xyallene 7, can proceed to -haloenones via two different paths:
a
Further extension of this chemistry to
a
-fluoroenones using
(a) react directly with NXS (X¼I or Br); (b) be further activated by
the same AuI catalyst to generate Au-containing cation A (Scheme
1). Path a will lead to oxocarbenium B with the halo group trans
to R1 (i.e., E-isomer) selectively as NXS should approach the more
electron-rich enolic C–C double bond from the less hindered face
(i.e., synperiplanar to H), while path b would afford product 4
with the halo group cis to R1 (i.e., Z-isomer) as our previous
studies13 suggested repeatedly a cis relationship between Au(PPh3)
and R1 in intermediates A and C26 and iodination of Au–C(sp2)
various electrophilic fluorine reagents such as SelectfluorÒ and N-
fluorobenzenesulfonimide was not successful under the estab-
lished reaction conditions.
Scheme 2 shows the proposed reaction mechanism using
propargylic acetates derived from aldehydes as substrate. An ini-
tial Au-catalyzed 3,3-rearrangement of the substrate is well
documented and highly likely;13,14 moreover, this acetoxy migra-
tion is necessary for regioselective installation of the carbonyl

M. Yu et al. / Tetrahedron 65 (2009) 1846–1855
1849
Table 3
Formation of b,b-disubstituted a-iodoenones
R1
O
OAc
Au(PPh3)NTf2 (2 mol %), NIS (1.2 eq)
acetone:H2O = 800:1, 0 °C, 2 h
R1
R2
R3
R2
R3
I
6
5
Entrya
1
Propargylic acetate 5
a
-Iodoenone 6
Yieldb [%]
96
OAc
Me
O
O
O
Me
Me
Me
5a
5b
5c
5d
5e
5f
6a
6b
6c
6d
6e
6f
Me
Me
3
I
I
3
OAc
OAc
OAc
OAc
Me
Me
Me
2
3
4
5
6
87
91
3
3
Me
3
Me
I
3
O
99
Me
3
I
3
Me
O
Me
Me Me
OAc
88c
96
Me
Me
3
Me
Me
I
3
O
I
OAc
O
7
5g
6g
83
Ph
Ph
I
a
Substrate concentration is 0.05 M.
Isolated yield.
Z/E¼1:2.2.
b
c
bonds18 is stereospecific or highly stereoselective. These two
paths yield the same product but with opposite stereoselectivities.
To shed more light on the mechanism, reactions were run in NMR
tube and the Z/E ratios were monitored by 1H NMR. When
propargylic ester 3c with all alkyl substituents was treated with
NIS and Ph3PAuNTf2 (2 mol %), a constant Z/E ratio of 19:1 was
observed during the reaction while the intermediate carbo-
xyallene was not detected. Quite on the opposite, when ester 3e
with a phenyl group at the propargylic position was studied, an
H2O played a key role in controlling the stereoselectivity of the
reaction studied during reaction condition optimization. Our pro-
posed mechanism offers ready explanation: under anhydrous con-
ditions where only small amount of adventitious H2O was present,
hydrolysis of A is very slow and, therefore, A can equilibrate back to 7.
As discussed previously, accumulation of 7 would make path a sig-
nificant, leading to increased amount of the E-isomer and decreased
selectivity(Table 1,entry1).WhensufficientamountofH2Oispresent,
hydrolysis of A into C is fast, therefore affording Z-2 highly selective.
The potential influence of H2O on the Au(I) complex is worth
discussing. Cationic Ph3PAu(I) complexes are known to react with
H2O under basic conditions to form [(Ph3PAu)3O]þXꢁ.28 In our re-
action, it is unlikely that Ph3PAuNTf2 is converted into
[(Ph3PAu)3O]þNTf2ꢁ in the presence of H2O as the trisgold(I)oxonium
complex should not be formed in a significant amount under acidic
conditions. Moreover, this trigold(I)oxonium complex was not cata-
lytically active enough as only 6% of 2 was formed in 4.5 h (Table 1,
entry 10). Nolan and co-workers proposed ItBuAuOH as the catalyst
for their enone formation reaction from propargylic acetates involv-
ing gold–allenolate intermediates in THF/H2O.14 Although Ph3PAuOH
might be formed along with HNTf2 in equilibrium with Ph3PAuNTf2
and H2O, the formation of a similar Ph3PAu–allenolate intermediate
(i.e., D, Scheme 3) is less likely in our system: firstly, it cannot explain
the observed high Z-stereoselectivities with aliphatic substrates as
opposite stereoselectivity (Z/E¼1:2) with the E-
a-iodoenone
slightly favored was detected invariably throughout the reaction.
Interestingly, in this case, 90% of substrate 3e was converted into
carboxyallene 7 in 5 min while the completion of the reaction
took much longer (30 min). The accumulation of 7 in this case
allows path a to participate, which can explain the low and op-
posite stereoselectivity. Moreover, when a 1:1 mixture of 3e and
its corresponding carboxyallene27 was mixed with NIS without
the AuI catalyst, the carboxyallene reacted to yield E-4e pre-
dominantly (Z/E¼1:6 throughout the reaction) while 3e remained
unchanged. These studies suggest that substrates with all alkyl
substituents proceed predominantly along path b, where carbo-
xyallene 7 is a transient intermediate and is converted into A and
eventually C rapidly in the presence of the AuI catalyst and H2O;
on the contrary, aryl-containing esters such as 3d, 3e, 3f, and 3g
reacted via both paths a and b due to facile 3,3-rearrangement
and substantial accumulation of 7, thus leading to diminished or
even opposite stereoselectivities.
iodination of D should favor the formation of E-a-haloenones due to
sterics; secondly, this approach cannot explain the observed forma-
tion of acetoxyallenes during the reaction (e.g., in the case of 3e).

1850
M. Yu et al. / Tetrahedron 65 (2009) 1846–1855
Table 4
Reaction scope for the formation of
a
-bromoenones
OAc
R1
O
Au(PPh3)NTf2 (2 mol %), NBS (1.1 eq)
acetone:H2O = 800:1, 0 °C, 2 h
R1
R2
R3
R2
R3
Br
8
3 or 5
Entrya
1
Propargylic acetate
a
-Bromoenones 8
Z/E
Yieldb [%]
85
OAc
O
Me
1
8a
>99:1
Me
Me
Me
3
Br
Me
3
OAc
O
Me
Me Me
Me
Me
2
3
4
5e
5d
5f
8b
8c
8d
1:1.4
d
93
95
96
3
Me
Me Br
3
OAc
O
Me
Me
3
Br
3
OAc
O
d
Br
OAc
O
5
3e
8e
1:5
86c
Br
a
Substrate concentration is 0.05 M.
Isolated yield.
AgNTf2 (10 mol %) was added.
b
c
O
O
O
NTf2
O
Me
O
Me
O
Me
R2
Au(PPh3)NTf2
(Ph3P)Au
R1
R1
R2
3,3-rearrangement
R1
O
•
R2
7
A
H
path a
NTf2
path b
H
hydrolysis
HNTf2
N
X
O
O
O
N
X
O
O
O
Me
X
Ph3PAu
R1
hydrolysis
O
R2
R2
X
R2
R1
4
B
R1
C
path a: E-selective
Z-selective
E-selective
path b: Z-selective
Scheme 2. Proposed reaction mechanism.
In summary, we have developed an efficient synthesis of linear
-haloenones from readily accessible propargylic acetates. This
a
reaction not only has broad substrate scopes but also offers good to
excellent Z-selectivities in the case of aliphatic propargylic acetates
derived from aldehydes. The low catalyst loading (2 mol %), mostly
excellent yields (75–99%), and mild reaction conditions (0 ꢀC and
2 h) are additional features that promise this reaction as a highly
+
HNTf2
Ac
PPh3AuNTf2
AuPPh3
H2O
+
Ph3PAuOH
Ph3PAu
O
O
OAc
H
O
R1
•
R2
R1
useful method for practical a-haloenone preparation.
R1
R2
R2
HOAc
H
D
3. Experimental
AuPPh3
R2
O
O
NXS
X
X
R2
3.1. General information
R1
R1
Anhydrous acetone was purchased from Acros Organics and
used without further purification. Anhydrous tetrahydrofuran in
Scheme 3. Further mechanistic considerations.

M. Yu et al. / Tetrahedron 65 (2009) 1846–1855
1851
Pure-PacÔ from Aldrich was used directly without further purifi-
cation. Flash column chromatography was performed over silicycle
silica gel (230–400 mesh). 1H NMR and 13C NMR spectra were
recorded on a Varian 500 MHz Unity plus spectrometer and a Var-
ian 400 MHz spectrometer using residue solvent peaks as internal
standards. Infrared spectra were recorded with a Perkin Elmer FT-IR
spectrum 2000 spectrometer and are reported in reciprocal centi-
meter (cmꢁ1). Mass spectra were recorded with Waters micromass
ZQ detector using electron spray method.
1743, 1599, 1491, 1444, 1372; MS (ESþ) calculated for
[C12H12NaO2]þ: 211.1; found: 210.9.
3.2.6. 3-Cyclohexyl-1-phenylprop-2-ynyl acetate (3e)
Yield: 94%. 1H NMR (400 MHz, CDCl3)
d 7.55–7.51 (m, 2H), 7.39–
7.31 (m, 3H), 6.49 (d, 1H, J¼2.0 Hz), 2.49–2.44 (m, 1H), 2.09 (s, 3H),
1.82–1.79 (m, 2H), 1.73–1.66 (m, 2H), 1.54–1.43 (m, 3H), 1.36–1.26
(m, 3H); 13C NMR (100 MHz, CDCl3)
d 169.9, 137.8, 128.7, 128.5,
127.7, 92.3, 76.6, 66.0, 32.37, 32.35, 29.1, 25.8, 24.8, 21.2; IR (neat):
3090, 3066, 3035, 2932, 2855, 2236, 1742, 1604, 1588, 1495, 1450,
1369; MS (ESþ) calculated for [C17H20NaO2]þ: 279.1; found: 279.1.
3.2. General procedure A: preparation of propargylic acetates
To a solution of a terminal alkyne (11 mmol) in anhydrous THF
(42 mL) at ꢁ78 ꢀC under N2 was added n-BuLi (2.5 M solution in
hexanes, 4.2 mL, 10.5 mmol). The reaction mixture was stirred at
the same temperature for 15 min before the addition of a ketone/
aldehyde (10 mmol). The resulting mixture was allowed to warm to
0 ꢀC gradually and stirred for an additional hour. Upon the addition
of acetic anhydride (2.4 mL, 25 mmol), the reaction mixture was
warmed to room temperature and stirred for 2 h before quenched
with aqueous NaHCO3. The mixture was extracted with Et2O
(3ꢂ30 mL), and the combined organic phases were washed with
water and brine, dried with anhydrous MgSO4, and filtered. The
filtrate was concentrated, and the residue was purified through
silica gel flash column chromatography (hexanes/ethyl
acetate¼20:1) to yield the desired acetate.
3.2.7. 1-(4-Methoxyphenyl)hept-2-ynyl acetate (3f)
Yield: 87%. 1H NMR (500 MHz, CDCl3)
d
7.46 (d, 2H, J¼8.5 Hz),
6.89 (d, 2H, J¼8.5 Hz), 6.42 (s,1H), 3.81 (s, 3H), 2.27 (t, 2H, J¼7.0 Hz),
2.07 (s, 3H), 1.52 (quintet, 2H, J¼7.2 Hz), 1.41 (sextet, 2H, J¼7.2 Hz),
0.91 (t, 3H, J¼7.2 Hz); 13C NMR (125 MHz, CDCl3)
d 170.0, 159.9,
129.9, 129.3, 113.8, 88.1, 76.8, 65.8, 55.3, 30.5, 21.9, 21.2, 18.5, 13.6; IR
(neat): 3072, 3037, 3003, 2959, 2935, 2873, 2838, 2292, 2234, 1741,
1611, 1587, 1514, 1465, 1443, 1428, 1369, 1343, 1305, 1279, 1251,
1229, 1175, 1144, 1110, 1034, 1015, 952, 909, 832; MS (ESþ) calcu-
lated for [C16H20NaO3]þ: 283.3; found: 283.2.
3.2.8. 1-(4-Trifluoromethylphenyl)hept-2-ynyl acetate (3g)
Yield: 85%. 1H NMR (400 MHz, CDCl3)
d 7.63 (s, 1H), 6.48 (t, 1H,
J¼2.0 Hz), 2.27 (td, 2H, J¼7.2, 2.4 Hz), 2.11 (s, 3H), 1.52 (quintet, 2H,
J¼7.2 Hz), 1.40 (sextet, 2H, J¼7.2 Hz), 0.91 (t, 3H, J¼7.2 Hz); 13C NMR
3.2.1. 1-Methylhept-2-ynyl acetate (1)
(100 MHz, CDCl3)
d
169.7, 141.5, 130.8 (q, JC–F¼32 Hz), 127.9, 125.6
Yield: 86%. 1H NMR (400 MHz, CDCl3)
d
5.44 (qt, 1H, J¼6.8,
(q, JC–F¼3.7 Hz), 123.9 (q, JC–F¼270.0 Hz), 89.2, 76.0, 65.3, 30.4, 21.9,
21.0, 18.5, 13.5; IR (neat): 3067, 2962, 2935, 2876, 2295, 2236, 1928,
1746, 1622, 1590, 1468,1422,1371,1327, 1227, 1168,1129, 1109, 1068,
1018, 959, 922, 850, 836; MS (ESþ) calculated for [C16H17NaO2]þ:
321.3; found: 321.2.
2.0 Hz), 2.20 (td, 2H, J¼7.0, 2.0 Hz), 2.06 (s, 3H), 1.53–1.34 (m, 7H),
0.91 (t, 3H, J¼7.2 Hz); 13C NMR (100 MHz, CDCl3)
d 170.0, 85.6, 78.6,
60.9, 30.6, 21.9, 21.8, 21.2, 18.4, 13.6; IR (neat): 2989, 2960, 2937,
2874, 2249, 1744, 1467, 1453, 1371; MS (ESþ) calculated for
[C10H16NaO2]þ: 191.1; found: 191.0.
3.2.9. 1,1-Dimethylhept-2-ynyl acetate (5a)
3.2.2. 3-Cyclohexyl-1-methylprop-2-ynyl acetate (3a)
Yield: 74%. 1H NMR (500 MHz, CDCl3)
d
2.20 (t, 2H, J¼7.0 Hz),
Yield: 83%. 1H NMR (500 MHz, CDCl3)
d
5.47 (qt, 1H, J¼6.5,
2.0 Hz), 2.40–2.36 (m, 1H), 2.07 (s, 3H), 1.79–1.67 (m, 4H), 1.50–1.39
(m, 7H), 1.32–1.27 (m, 2H); 13C NMR (125 MHz, CDCl3)
170.0, 89.5,
2.01 (s, 3H), 1.64 (s, 6H), 1.48 (p, 2H, J¼7.6 Hz), 1.39 (sextet, 2H,
J¼7.6 Hz), 0.90 (t, 3H, J¼7.6 Hz); 13C NMR (125 MHz, CDCl3)
d 169.4,
d
84.6, 81.3, 72.6, 30.6, 29.3, 22.1, 21.9, 18.4, 13.6; IR (neat): 2987,
2960, 2936, 2875, 2245, 1747, 1586, 1468, 1434, 1368, 1329, 1266,
1245, 1196, 1016, 953, 822; MS (ESþ) calculated for [C11H18NaO2]þ:
205.1; found: 205.1.
78.5, 60.9, 32.4, 28.9, 25.8, 24.8, 21.9, 21.2; IR (neat): 2988, 2933,
2856, 2244, 1741, 1592, 1450, 1317, 1340, 1309, 1224, 1170, 1592,
1450; MS (ESþ) calculated for [C12H18NaO2]þ: 217.3; found: 217.2.
3.2.3. 1-Butylhept-2-ynyl acetate (3b)
3.2.10. 1-Hex-1-ynylcyclopentyl acetate (5b)
Yield: 80%. 1H NMR (500 MHz, CDCl3)
d
5.35 (t, 1H, J¼6.5 Hz),
Yield: 70%. 1H NMR (400 MHz, CDCl3)
d 2.22–2.15 (m, 4H), 2.12–
2.21 (td, 2H, J¼7.0, 1.7 Hz), 2.07 (s, 3H), 1.77–1.69 (m, 2H), 1.49
2.04 (m, 2H), 2.02 (s, 3H), 1.74–1.70 (m, 4H), 1.50–1.44 (m, 2H), 1.43–
(quintet, 2H, J¼7.2 Hz), 1.43–1.31 (m, 6H), 0.93–0.89 (m, 6H); 13C
1.35 (m, 2H), 0.90 (t, 3H, J¼7.6 Hz); 13C NMR (100 MHz, CDCl3)
d 169.7,
NMR (125 MHz, CDCl3)
d
170.1, 86.1, 77.6, 64.6, 34.8, 30.6, 27.2, 22.2,
85.3, 81.0, 80.5, 40.5, 30.7, 23.2, 21.9,18.5, 13.6; IR (neat): 2960, 2933,
2875, 2246, 1746, 1593, 1453, 1435, 1367, 1334, 1241, 1124, 1016, 970;
MS (ESþ) calculated for [C13H20NaO2]þ: 231.1; found: 231.1.
21.9, 21.2, 18.4, 13.9, 13.6; IR (neat): 2959, 2935, 2871, 2864, 2242,
1743, 1468, 1433, 1371, 1351, 1234, 1161, 1108, 1019, 959; MS (ESþ)
calculated for [C13H22NaO2]þ: 233.3; found: 233.3.
3.2.11. 1-Hex-1-ynylcyclohexyl acetate (5c)
3.2.4. 1-Cyclohexylhept-2-ynyl acetate (3c)
Yield: 84%. 1H NMR (400 MHz, CDCl3)
d
2.254 (t, 2H, J¼7.2 Hz),
Yield: 84%. 1H NMR (500 MHz, CDCl3)
d
5.20 (d, 1H, J¼6.0 Hz),
2.11–2.06 (m, 2H), 2.03 (s, 3H), 1.84–1.77 (m, 2H), 1.63–1.29 (m, 10H),
2.21 (t, 2H, J¼7.0 Hz), 2.07 (s, 3H), 1.84–1.58 (m, 5H), 1.49 (quintet,
2H, J¼7.2 Hz), 1.39 (sextet, 2H, J¼7.2 Hz), 1.27–1.03 (m, 6H), 0.90 (t,
0.91 (t, 3H, J¼7.2 Hz); 13C NMR (100 MHz, CDCl3)
d 169.3, 86.8, 80.0,
76.1, 37.4, 30.8, 25.3, 22.7, 22.1, 21.9, 18.5, 13.6; IR (neat): 2936, 2861,
2244, 1746, 1600, 1447, 1431, 1367, 1301, 1264, 1230, 1184, 1131, 1034,
1020, 965;MS (ESþ)calculatedfor[C14H22NaO2]þ: 245.2;found:245.1.
3H, J¼7.2 Hz); 13C NMR (125 MHz, CDCl3)
d 170.2, 86.8, 76.4, 68.8,
42.0, 30.6, 28.6, 28.0, 26.2, 25.8, 25.7, 21.9, 21.1, 18.4, 13.6; IR (neat):
2960, 2931, 2856, 2239,1742,1593,1452,1432,1370,1231,1119,1018,
977; MS (ESþ) calculated for [C15H24NaO2]þ: 259.4; found: 259.2.
3.2.12. 1-Hex-1-ynylcycloheptyl acetate (5d)
Yield: 70%. 1H NMR (400 MHz, CDCl3)
d
2.24–2.17 (m, 4H), 2.06–
2.04 (m, 2H), 2.01 (s, 3H), 1.57–1.37 (m, 12H), 0.90 (t, 3H, J¼7.2 Hz);
13C NMR (100 MHz, CDCl3)
169.4, 86.0, 81, 2, 79.5, 40.5, 30.7, 28.2,
3.2.5. 1-Methyl-3-phenylprop-2-ynyl acetate (3d)
Yield: 86%. 1H NMR (400 MHz, CDCl3)
d
7.45–7.43 (m, 2H), 7.33–
d
7.27 (m, 3H), 5.67 (q, 1H, J¼6.6 Hz), 2.11 (s, 3H), 1.58 (d, 3H,
22.2, 21.9, 18.5, 13.6; IR (neat): 2936, 2861, 2244, 1746, 1600, 1447,
1431, 1367, 1301, 1264, 1230, 1184, 1131, 1034, 1020, 965; MS (ESþ)
calculated for [C15H24NaO2]þ: 257.2; found: 259.2.
J¼6.6 Hz); 13C NMR (100 MHz, CDCl3)
d 169.9, 131.8, 128.6, 128.2,
122.2, 87.4, 84.5, 60.8, 21.5, 21.1; IR (neat): 3058, 2990, 2939, 2247,

1852
M. Yu et al. / Tetrahedron 65 (2009) 1846–1855
3.2.13. 1-Isopropyl-1-methylhept-2-ynyl acetate (5e)
3.3.2. 4-Acetoxydec-5-ynyl acetate (3i)
Yield: 80%. 1H NMR (400 MHz, CDCl3)
d 5.40–5.38 (m, 1H), 4.10
Yield: 80%. 1H NMR (400 MHz, CDCl3)
d
2.23 (t, 2H, J¼7.2 Hz),
2.16 (heptet, 1H, J¼6.6 Hz), 2.01 (s, 3H), 1.61 (s, 3H), 1.53–1.43 (m,
2H), 1.42–1.37 (m, 2H), 1.01 (d, 3H, J¼6.6 Hz), 0.97 (d, 3H, J¼6.6 Hz),
(t, 2H, J¼4.8 Hz), 2.21 (t, 2H, J¼6.8 Hz), 2.08 (s, 3H), 2.06 (s, 3H),
1.83–1.74 (m, 4H), 1.48 (sextet, 2H, J¼8 Hz), 1.39 (sextet, 2H,
0.90 (t, 3H, J¼7.2 Hz); 13C NMR
d
(100 MHz, CDCl3)
d
169.4, 86.2,
J¼8 Hz), 0.91 (t, 3H, J¼7.6 Hz); 13C NMR (100 MHz, CDCl3)
d 171.1,
79.6, 79.2, 37.4, 30.8, 23.5, 22.1, 21.9, 18.4, 17.5, 17.2, 13.6; IR (neat):
2965, 2936, 2876, 2244, 1746, 1559, 1458, 1436, 1371, 1336, 1243,
1129, 1060, 1014, 942; MS (ESþ) calculated for [C13H22NaO2]þ:
233.2; found: 233.2.
170.0, 86.7, 64.0, 63.9, 31.7, 30.5, 24.3, 21.9, 21.1, 21.0, 18.4, 13.6; IR
(neat): 3308, 2960, 2935, 2337, 1741, 1592, 1430, 1370, 1232, 1023;
MS (ESþ) calculated for [C14H22NaO4]þ: 277.1; found: 277.2.
3.4. Au(I)-catalyzed formation of a-haloenones
3.2.14. 1-Cyclohexylethynylcyclohexyl acetate (5f)
Yield: 91%. 1H NMR (400 MHz, CDCl3)
d
2.47–2.43 (m, 1H), 2.13–
2.08 (m, 2H), 2.02 (s, 3H), 1.82–1.24 (m, 18H); 13C NMR (100 MHz,
CDCl3) 169.2, 91.0, 80.2, 76.2, 37.5, 32.6, 28.9, 26.0, 25.3, 24.6, 22.9,
To a solution of propargylic acetate 3 or 5 (0.2 mmol) in anhy-
drous acetone (4 mL) cooled in ice-water bath were added H2O
(0.005 ml, 1.39 equiv) and Au(PPh3)NTf2 (0.05 M in acetone,
0.08 mL). The solution was treated with NIS (0.24 mmol, 1.2 equiv)
or NBS (0.22 mmol, 1.1 equiv). The reaction mixture was stirred for
2 h before quenched with NEt3 (one drop) and aqueous Na2S2O3
(5 mL). The mixture was extracted with Et2O (3ꢂ8 mL). The com-
bined organic phases were washed with H2O (10 mL) and brine
(10 mL), dried with anhydrous MgSO4, and filtered. The filtrate was
concentrated, and the residue was purified through silica gel flash
column chromatography (hexanes/ethyl acetate¼50:1) to yield the
d
22.2; IR (neat): 2933, 2857, 2663, 2237, 1746, 1615, 1447, 1367, 1229,
1184, 1022; MS (ESþ) calculated for [C16H24NaO2]þ: 271.2; found:
271.1.
3.2.15. 1-Phenylethynylcyclohexyl acetate (5g)
Yield: 88%. 1H NMR (500 MHz, CDCl3)
d 7.46–7.44 (m, 2H), 7.29–
7.28 (m, 3H), 2.24–2.19 (m, 2H), 2.07 (s, 3H),1.93–1.88 (m, 2H),1.70–
1.65 (m, 4H), 1.59–1.53 (m, 1H), 1.39–1.33 (m, 1H); 13C NMR
(125 MHz, CDCl3)
d
169.2, 131.8, 128.2, 128.1, 122.8, 89.1, 86.2, 75.9,
desired a-haloenone.
37.1, 25.2, 22.7, 22.0; IR (neat): 3082, 3057, 3035, 3023, 2937, 2861,
2667, 2229, 2203, 1743, 1675, 1599, 1573, 1491, 1444, 1367, 1346,
1312, 1264, 1229, 1163, 1138, 1071, 1041, 1022, 959; MS (ESþ) cal-
culated for [C16H18NaO2]þ: 265.3; found: 265.2.
3.4.1. 3-Iodooct-2-en-4-one (2)
Yield: 89%. Z/E¼45:1. 1H NMR (400 MHz, CDCl3) (major isomer)
d
7.11 (q, 1H, J¼6.8 Hz), 2.81 (t, 2H, J¼7.6 Hz), 2.07 (d, 3H, J¼6.8 Hz),
1.63 (quintet, 2H, J¼7.6 Hz), 1.34 (sextet, 2H, J¼7.6 Hz), 0.92 (t, 3H,
J¼7.6 Hz); 13C NMR (125 MHz, CDCl3) (major isomer)
d 194.9, 146.8,
3.3. General procedure for propargylic acetates 3h and 3i
114.3, 37.5, 30.3, 27.1, 23.9, 22.3,13.8;IR (neat):2958, 2932, 2871,1702,
1683, 1611, 1464, 1413, 1373, 1288, 1262, 1238, 1288, 1262, 1238, 1171,
1113, 1072; MS (ESþ) calculatedfor [C8H13NaIO]þ:275.0;found:275.0.
A solution of 1-hexyne (1.30 g, 15.8 mmol) in THF (50 ml) was
cooled to ꢁ78 ꢀC in a dry ice-acetone bath under nitrogen, and n-
BuLi (1.6 M in hexanes, 9.17 mL, 14.64 mmol) was added dropwise
in 15 min. After addition, a solution of 4-(tert-butyldimethylsilyl-
oxy)propionaldehyde (for 3h, 2.3 g, 12.2 mmol) or 4-(tert-butyldi-
methylsilyloxy)butyraldehyde (for 3i, 2.5 g, 12.2 mmol) in THF
(10 mL) was added dropwise, the resulting reaction mixture was
allowed to warm to room temperature gradually. The reaction was
quenched by the addition of saturated NH4Cl (30 mL). The aqueous
layer was extracted with Et2O (3ꢂ50 mL). The combined organic
layer was washed with brine (100 mL), dried with anhydrous
MgSO4, filtered, and concentrated to give an oil. The desired alcohol
was obtained as a clear liquid via bulb-to-bulb distillation (w50%
yield in two steps).
To a solution of the above alcohol (1 mmol) in THF (5 mL) was
added TBAF (1 M in THF, 1 mL). The resulting mixture was stirred at
room temperature for 2 h. The reaction mixture was cooled down
in an ice-water bath, and Et3N (0.3 mL, 3 mmol) and DMAP (cat.)
were added followed by dropwise addition of CH3COCl (0.18 mL,
2.5 mmol). The resulting mixture was allowed to rise to room
temperature and stirred for 4 h. The reaction was quenched by the
addition of water (20 mL). The organic layer was extracted with
Et2O (3ꢂ15 mL). The combined organic layer was washed with
brine (50 mL), dried with MgSO4, filtered, and concentrated to give
an oily residue, which was purified by flash column chromatogra-
phy to give diacetate 3h or 3i.
3.4.2. 1-Cyclohexyl-2-iodobut-2-en-1-one (4a)
Yield: 82%. Z/E¼12:1. 1H NMR (500 MHz, CDCl3) (major isomer)
d
7.08 (q, 1H, J¼7.0 Hz), 3.14 (q, 1H, J¼7.0 Hz), 2.08 (d, 3H,
J¼7.0 Hz), 1.80–1.78 (m, 4H), 1.48–1.22 (m, 6H); 13C NMR
(125 MHz, CDCl3) (major isomer)
d 198.2, 146.1, 113.9, 45.4, 29.9,
25.8, 25.7, 24.0; IR (neat): 3019, 2932, 2855, 2664, 1678, 1611,
1463, 1450, 1372, 1287, 1264, 1241, 1188, 1163, 1131, 1109, 1081,
1071, 1030, 974, 895, 884, 824; MS (ESþ) calculated for
[C10H15NaIO]þ: 301.0; found: 300.9.
3.4.3. 6-Iodoundec-6-en-5-one (4b)
Yield: 94%. Z/E¼10:1. 1H NMR (400 MHz, CDCl3)
d 6.99 (t, 1H,
J¼6.8 Hz), 2.82 (t, 2H, J¼7.2 Hz), 2.42 (q, 2H, J¼7.6 Hz),1.67–1.50 (m,
4H), 1.45–1.30 (m, 4H), 0.97–0.89 (m, 6H); 13C NMR (125 MHz,
CDCl3) d 195.0, 151.2, 112.4, 37.7, 37.6, 29.7, 27.1, 22.4, 22.3, 13.8, 13.8;
IR (neat): 3351, 2958, 2930, 2872, 2735, 1683, 1604, 1465, 1413,
1379, 1291, 1236, 1167, 1123, 1088, 934; MS (ESþ) calculated for
[C11H19INaO]þ: 317.0; found: 317.0.
3.4.4. 1-Cyclohexyl-2-iodohept-1-en-3-one (4c)
Yield: 91%. Z/E¼19:1. AgNTf2 (10 mol %) was added together
with Au(PPh3)NTf2 and a column basified with Et3N was used for
purification. 1H NMR (500 MHz, CDCl3)
d
6.74 (d, 1H, J¼9 Hz), 2.80
(t, 2H, J¼15 Hz), 2.60–2.52 (m, 1H), 1.82–1.68 (m, 5H), 1.60 (quintet,
2H, J¼7.5 Hz), 1.41–1.31 (m, 4H), 1.27–1.20 (m, 3H), 1.92 (t, 3H,
3.3.1. 3-Acetoxynon-4-ynyl acetate (3h)
J¼7.5 Hz); 13C NMR (125 MHz, CDCl3)
d 195.3, 155.7, 109.9, 46.8,
Yield: 67%. 1H NMR (400 MHz, CDCl3)
d
5.47 (tt, 1H, J¼6.8,
37.6, 30.7, 27.2, 25.7, 25.2, 22.3, 13.8; IR (neat): 3351, 2928, 2852,
2662, 2351, 1683, 1601, 1448, 1278, 1224, 1169, 1128, 1089, 968; MS
(ESþ) calculated for [C13H21INaO]þ: 343.1; found: 343.0.
2.0 Hz), 4.25–4.15 (m, 2H), 2.20 (td, 2H, J¼6.8, 2.0 Hz), 2.13–2.03 (m,
8H), 1.51–1.45 (m, 2H), 1.41–1.36 (m, 2H), 0.90 (t, 3H, J¼6.8 Hz); 13C
NMR (125 MHz, CDCl3)
d 170.9, 170.0, 87.0, 76.5, 61.5, 60.4, 34.1,
30.4, 21.9, 21.0, 20.9, 18.3, 13.5; IR (neat): 2960, 2936, 2874, 2247,
1744, 1592, 1459, 1432, 1370, 1232, 1159, 1045, 960; MS (ESþ) cal-
culated for [C13H20NaO4]þ: 263.1; found: 263.2.
3.4.5. 2-Iodo-1-phenylbut-2-en-1-one (4d)
Yield: 75%. Z/E¼1.2:1. Compound Z-4d: 1H NMR (400 MHz,
CDCl3)
d
7.69 (d, 2H, J¼8 Hz), 7.55 (t, 2H, J¼8 Hz), 7.44 (t, 2H,

M. Yu et al. / Tetrahedron 65 (2009) 1846–1855
1853
J¼8 Hz), 6.73 (q, 1H, J¼8 Hz), 2.09 (d, 3H, J¼8 Hz); 13C NMR
3.4.9. 4-Iodonona-1,3-dien-5-one (4h)
Yield: 80%. 1H NMR (500 MHz, CDCl3)
(125 MHz, CDCl3)
d
191.9, 149.7, 135.8, 132.4, 129.6, 128.4, 110.5,
d
7.37 (d, 1H, J¼10 Hz),
23.6; IR (neat): 3297, 3059, 2924, 2851, 2356,1993,1658, 1606,1577,
1446, 1371, 1314, 1260, 1179, 1120, 1060, 1025, 965; MS (ESþ) cal-
culated for [C10H9INaO]þ: 295.0; found: 295.0. Compound E-4d: 1H
6.78 (td, 1H, J¼16.5, 10 Hz), 5.88 (d, 1H, J¼17 Hz), 5.76 (d, 1H,
J¼10 Hz), 2.87 (t, 2H, J¼7.5 Hz), 1.65 (quintet, 2H, J¼7.5 Hz), 1.36
(sextet, 2H, J¼7.5 Hz), 0.93 (t, 3H, J¼7.5 Hz); 13C NMR (125 MHz,
NMR (400 MHz, CDCl3)
d
7.98 (d, 2H, J¼8 Hz), 7.61 (t, 2H, J¼8 Hz),
CDCl3) d 195.4, 146.2, 139.3, 128.9, 110.6, 37.7, 27.1 22.3, 13.9; IR
7.49 (t, 2H, J¼8 Hz), 6.67 (q, 1H, J¼8 Hz), 1.67 (d, 3H, J¼8 Hz); 13C
(neat): 3274, 2958, 2331, 1682, 1597, 1456, 1597, 1457, 1261, 1123,
NMR (125 MHz, CDCl3) d 192.7,140.8,134.0,133.6,129.9,128.9, 90.4,
1042. MS (ESþ) calculated for [C9H13INaO]þ: 286.9; found: 286.6.
18.7; IR (neat): 3053, 2916, 2850, 2347, 1666, 1596, 1448, 1329, 1227,
1174, 1115, 1012; MS (ESþ) calculated for [C10H9INaO]þ: 295.0;
found: 295.0.
3.4.10. 4-Iodo-5-oxonon-3-enyl acetate (4i)
Yield: 83%. 1H NMR (400 MHz, CDCl3)
d
7.00 (t, 1H, J¼6.8 Hz),
4.13 (t, 2H, J¼6.4 Hz), 2.82 (t, 2H, J¼7.2 Hz), 2.50 (q, 2H,
J¼7.2 Hz), 2.07 (s, 3H), 1.90 (quintet, 2H, J¼7.2 Hz), 1.63 (quintet, 2H,
J¼7.6 Hz),1.35 (sextet, 2H, J¼7.6 Hz), 0.93 (t, 3H, J¼6.8 Hz); 13C NMR
3.4.6. 1-Cyclohexyl-2-iodo-3-phenylpropenone (4e)
Yield: 97%. Z/E¼1:2. Compound Z-4e: 1H NMR (500 MHz,
CDCl3)
d
7.96 (s, 1H), 7.75–7.70 (m, 2H), 7.46–7.43 (m, 3H), 3.33 (tt,
(125 MHz, CDCl3) d 194.9, 171.0, 149.8, 113.0, 63.5, 37.7, 34.6, 27.1,
1H, J¼11.5, 3 Hz), 1.92–1.83 (m, 4H), 1.74–1.72 (m, 1H), 1.54–1.46
26.7, 22.3, 21.0, 13.8; IR (neat): 3271, 2958, 2872, 1738, 1683, 1604,
1456, 1366, 1241, 1159, 1118, 1044; MS (ESþ) calculated for
[C12H19INaO3]þ: 361.0; found: 360.9.
(m, 2H), 1.42–1.23 (m, 3H); 13C NMR (125 MHz, CDCl3)
d
199.5,
145.6, 135.9, 130.0, 129.5, 128.3, 107.2, 45.6, 30.0, 25.8; IR (neat):
3334, 3057, 3023, 2930, 2853, 2662, 1674, 1591, 1491, 1445, 1366,
1262, 1186, 1150, 1112, 1013, 925; MS (ESþ) calculated for
[C15H17INaO]þ: 363.0; found: 362.9. Compound E-4e: 1H NMR
3.4.11. 3-Iodo-2-methyloct-2-en-4-one (6a)
Yield: 96%. 1H NMR (400 MHz, CDCl3)
d
2.81 (t, 2H, J¼7.2 Hz),
(500 MHz, CDCl3)
d
7.46 (s, 1H), 7.32–7.31 (m, 3H), 7.19–7.17 (m,
2.03 (s, 3H),1.96 (s, 3H),1.61 (quintet, 2H, J¼7.2 Hz),1.35 (sextet, 2H,
2H), 2.47 (tt, 1H, J¼11, 3.5 Hz), 1.82 (d, 2H, J¼11.5 Hz), 1.68–1.54 (m,
J¼7.2 Hz), 0.93 (t, 3H, J¼7.2 Hz); 13C NMR (125 MHz, CDCl3)
d 202.3,
2H), 1.58–1.54 (m, 1H), 1.39–1.32 (m, 2H), 1.16–1.02 (m, 3H); 13C
144.3, 95.5, 40.5, 30.3, 26.4, 22.3, 21.9, 13.8; IR (neat): 2958, 2932,
2873, 1688, 1601, 1464, 1441, 1406, 1380, 1368, 1258, 1238, 1155,
1105, 1044, 910, 842; MS (ESþ) calculated for [C9H15NaIO]þ: 289.0;
found: 289.0.
NMR (125 MHz, CDCl3)
d 206.3, 143.0, 136.7, 129.0, 129.6, 128.1,
96.3, 49.5, 29.5, 25.6, 25.6; IR (neat): 3352, 3057, 3024, 2930, 2853,
2662, 1687, 1598, 1572, 1494, 1448, 1366, 1312, 1289, 1236, 1141,
1071, 1007, 926, 814; MS (ESþ) calculated for [C15H17INaO]þ: 363.0;
found: 362.9.
3.4.12. 1-Cyclopentylidene-1-iodohexan-2-one (6b)
Yield: 87%. 1H NMR (400 MHz, CDCl3)
d
2.85 (t, 2H, J¼7.2 Hz),
3.4.7. 2-Iodo-1-(4-methoxyphenyl)hept-1-en-3-one (4f)
2.70 (tt, 2H, J¼7.2, 1.2 Hz), 2.47 (tt, 2H, J¼7.2, 1.2 Hz), 1.89 (quintet,
2H, J¼7.2 Hz), 1.72 (quintet, 2H, J¼7.2 Hz), 1.58 (quintet, 2H,
J¼7.2 Hz), 1.34 (sextet, 2H, J¼7.2 Hz), 0.92 (t, 3H, J¼7.2 Hz); 13C NMR
Yield: 84%. Z/E¼1.05:1. Compound Z-4f: 1H NMR (400 MHz,
CDCl3)
d
8.02 (s, 1H), 7.90 (d, 2H, J¼8.8 Hz), 6.98 (d, 2H, J¼8.8 Hz),
3.87 (s, 3H), 2.97 (t, 2H, J¼8 Hz), 1.70 (quintet, 2H, J¼7.2 Hz), 1.39
(125 MHz, CDCl3) d 198.9, 166.4, 92.3, 44.4, 41.8, 36.1, 28.7, 26.9,
(sextet, 2H, J¼7.6 Hz), 0.95 (t, 3H, J¼7.2 Hz); 13C NMR (125 MHz,
24.9, 22.3, 13.9; IR (neat): 2959, 2936, 2872, 1674, 1573, 1466, 1452,
1413, 1379, 1306, 1289, 1264, 1172, 1158, 1137, 1088, 911; MS (ESþ)
calculated for [C11H17NaIO]þ: 315.0; found: 315.0.
CDCl3)
d 195.9, 161.4, 146.1, 132.0, 127.6, 113.8, 104.6, 55.4, 37.8,
27.4, 22.4, 13.9; IR (neat): 3003, 2957, 2932, 2871, 2838, 1674,
1604, 1587, 1568, 1509, 1463, 1255, 1148, 1029, 826; MS (ESþ)
calculated for [C14H17INaO2]þ: 367.0; found: 366.9. Compound E-
3.4.13. 1-Cyclohexylidene-1-iodohexan-2-one (6c)
4f: 1H NMR (400 MHz, CDCl3)
d
7.36 (s, 1H), 7.13 (d, 2H,
Yield: 91%. 1H NMR (400 MHz, CDCl3)
d
2.79 (t, 2H, J¼7.2 Hz),
J¼8.8 Hz), 6.84 (d, 2H, J¼8.8 Hz), 3.81 (s, 3H), 2.54 (t, 2H,
2.41 (t, 2H, J¼5.6 Hz), 2.33 (t, 2H, J¼5.6 Hz), 1.66–1.50 (m, 8H), 1.35
J¼7.6 Hz), 1.56 (quintet, 2H, J¼7.2 Hz), 1.24 (sextet, 2H, J¼7.6 Hz),
(sextet, 2H, J¼7.2 Hz), 0.93 (t, 3H, J¼7.2 Hz); 13C NMR (125 MHz,
0.83 (t, 3H, J¼7.2 Hz); 13C NMR (125 MHz, CDCl3)
d
203.9, 160.2,
CDCl3) d 202.5, 149.2, 92.4, 40.3, 39.6, 32.9, 28.0, 27.4, 26.3, 25.9,
142.6, 129.7, 129.2, 114.0, 94.7, 55.3, 40.2, 26.4, 22.1, 13.7; IR
(neat): 3271, 2957, 2930, 2870, 1685, 1604, 1509, 1456, 1293,
1255, 1178, 1122, 1032; MS (ESþ) calculated for [C14H17INaO2]þ:
267.0; found: 267.0.
22.3, 13.8; IR (neat): 2957, 2932, 2857, 1694, 1606, 1464, 1448, 1404,
1350, 1260, 1221, 1145, 1077, 1069, 984, 854; MS (ESþ) calculated for
[C12H19NaIO]þ: 329.0; found: 329.0.
3.4.14. 1-Cycloheptylidene-1-iodohexan-2-one (6d)
3.4.8. 2-Iodo-1-(4-trifluoromethylphenyl)hept-1-en-3-one (4g)
Yield: 96%. Z/E¼5:1. Compound Z-4g: 1H NMR (400 MHz, CDCl3)
Yield: 99%. 1H NMR (400 MHz, CDCl3)
d
2.80 (t, 2H, J¼7.2 Hz),
2.47–2.42 (m, 4H), 1.69–1.49 (m, 10H), 1.35 (sextet, 2H, J¼7.2 Hz),
d
8.00 (s, 1H), 7.81 (d, 2H, J¼8.4 Hz), 7.70 (d, 2H, J¼8.4 Hz), 2.99 (t,
0.93 (t, 3H, J¼7.2 Hz); 13C NMR (125 MHz, CDCl3)
d 202.4,151.4, 96.1,
2H, J¼7.2 Hz), 1.71 (quintet, 2H, J¼7.2 Hz), 1.40 (sextet, 2H,
41.5, 40.4, 33.5, 29.2, 28.5, 28.0, 26.4, 26.1, 22.3, 13.8; IR (neat):
2956, 2927, 2857, 1688, 1599, 1464, 1457, 1404, 1351, 1266, 1160,
1132, 1081, 957, 909; MS (ESþ) calculated for [C13H21NaIO]þ: 343.0;
found: 343.0.
J¼7.2 Hz), 0.96 (t, 3H, J¼7.2 Hz); 13C NMR (125 MHz, CDCl3)
d 196.2,
144.8, 139.8, 131.6 (q, JC–F¼32.4 Hz), 129.8, 125.6 (q, JC–F¼3.72 Hz),
124.0 (q, JC–F¼270.8 Hz), 110.2, 38.4, 27.3, 22.5, 14.1; IR (neat): 3070,
2960, 2934, 2874, 1681, 1598, 1466, 1412, 1324, 1168, 1128, 1068,
1017, 885, 827; MS (ESþ) calculated for [C14H14NaF3IO]þ: 405.0;
3.4.15. 4-Iodo-2,3-dimethylnon-3-en-5-one (6e)
found: 404.9. Compound E-4g: 1H NMR (400 MHz, CDCl3)
d
7.58 (d,
Yield: 88%. Z/E¼1:2.31. 1H NMR (500 MHz, CDCl3) (major iso-
2H, J¼8.4 Hz), 7.38 (s, 1H), 7.31 (d, 2H, J¼8.4 Hz), 2.55 (t, 2H,
mer)
d
2.83 (quintet, 1H, J¼7.0 Hz), 2.79 (t, 2H, J¼7.5 Hz), 1.88 (s,
J¼7.2 Hz), 1.56 (quintet, 2H, J¼7.2 Hz), 1.24 (sextet, 2H, J¼7.2 Hz),
3H), 1.61 (quintet, 2H, J¼7.5 Hz), 1.35 (quintet, 2H, J¼7.5 Hz), 1.02 (d,
0.83 (t, 3H, J¼7.2 Hz); 13C NMR (125 MHz, CDCl3)
d 203.0, 140.7,
6H, J¼7.0 Hz), 0.93 (t, 3H, J¼7.5 Hz); 1H NMR (500 MHz, CDCl3)
139.5, 130.7 (q, JC–F¼32.4 Hz), 128.2, 125.7 (q, JC–F¼3.75 Hz), 123.8
(q, JC–F¼270.6 Hz), 99.68, 40.0, 26.0, 22.0, 13.7; IR (neat): 3070,
2960, 2923, 2870, 1699, 1597, 1459, 1421, 1324, 1168, 1126, 1068,
1017, 874, 830; MS (ESþ) calculated for [C14H14NaF3IO]þ: 405.0;
found: 404.9.
(minor isomer)
d
2.94 (quintet, 1H, J¼7.0 Hz), 2.78 (t, 2H, J¼7.5 Hz),
1.77 (s, 3H), 1.61 (quintet, 2H, J¼7.5 Hz), 1.35 (quintet, 2H, J¼7.5 Hz),
1.02 (d, 6H, J¼7.0 Hz), 0.93 (t, 3H, J¼7.5 Hz); 13C NMR (125 MHz,
CDCl3) (major isomer)
d 202.5, 150.6, 95.9, 40.3, 39.8, 33.5, 26.3,
22.3, 21.0, 19.7, 13.8; 13C NMR (125 MHz, CDCl3) (minor isomer)

1854
M. Yu et al. / Tetrahedron 65 (2009) 1846–1855
d
202.7, 149.5, 93.9, 40.3, 39.8, 33.5, 26.3, 22.3, 21.6, 14.6, 13.8; IR
3.4.22. 2-Bromo-1-cyclohexyl-3-phenylpropenone (8e)
(neat): 2962, 2932, 2872, 1695, 1620, 1615, 1464, 1404, 1385, 1363,
1342, 1225, 1151, 1101, 1062, 983, 900; MS (ESþ) calculated for
[C11H19NaIO]þ: 317.1; found: 317.0.
Yield: 93%. Z/E¼1:6. Compound E-8e: 1H NMR (500 MHz, CDCl3)
d
7.26–7.25 (m, 3H), 7.19 (s, 1H), 7.14–7.13 (m, 2H), 2.45 (tt, 1H,
J¼11.5, 3.5 Hz), 1.77–1.75 (m, 2H), 1.64–1.61 (m, 2H), 1.31–1.22 (m,
4H), 1.08–0.98 (m, 2H); 13C NMR (125 MHz, CDCl3)
d
204.3, 138.8,
3.4.16. 1-Cyclohexyl-2-cyclohexylidene-2-iodoethanone (6f)
135.9,130.4,128.7,128.2,119.7, 49.4, 28.7, 25.7, 25.5; IR (neat): 3059,
3026, 2931, 2854, 1695, 1602, 1575, 1447, 1144, 928, 754, 697; MS
(ESþ) calculated for [C15H17NaBrO]þ: 315.1; found: 315.0.
Yield: 96%. 1H NMR (500 MHz, CDCl3)
d
3.03 (tt,1H, J¼11, 3.0 Hz),
2.42 (t, 2H, J¼7.5 Hz), 2.30 (t, 2H, J¼6 Hz), 1.92 (d, 2H, J¼12.5 Hz),
1.80–1.77 (m, 2H), 1.69–1.50 (m, 7H), 1.41–1.10 (m, 5H); 13C NMR
3.5. Preparation of [(Ph3PAu)3O]DNTf2L
(125 MHz, CDCl3)
d 204.9, 149.4, 91.8, 47.5, 39.6, 33.4, 28.8, 28.0,
27.4, 25.9, 25.8, 25.7; IR (neat): 3351, 2930, 2853, 2609, 1684, 1616,
1448, 1350, 1309, 1219, 1149, 1084, 982; MS (ESþ) calculated for
[C14H21INaO]þ: 355.0; found: 355.0.
To a solution of Ph3PAuNTf2 (74 mg, 0.1 mmol) in methanol
(10 mL) at room temperature under nitrogen was added KOH
(10 mg, 0.178 mol) and NaNTf2 (137 mg, 0.455 mmol). The resulting
mixture was stirred at room temperature for 1 h. The reaction
mixture was concentrated and the residue was extracted with
chloroform (3 mLꢂ2). After filtration, hexane (20 mL) was added to
the filtrate. The precipitation was collected by filtration, washed
with hexanes (10 mL), and dried under vacuum to afford the de-
sired Au complex (46 mg, yield 88%). 1H NMR (500 MHz, CDCl3)
3.4.17. 2-Cyclohexylidene-2-iodo-1-phenylethanone (6g)
Yield: 83%. 1H NMR (400 MHz, CDCl3)
d
7.98 (d, 2H, J¼8 Hz), 7.50
(t, 1H, J¼7.6 Hz), 7.48 (t, 2H, J¼7.6 Hz), 2.55 (t, 2H, J¼6 Hz), 2.22 (t,
2H, J¼6 Hz),1.75–1.69 (m, 2H), 1.60–1.54 (m, 2H),1.47–1.42 (m, 2H);
13C NMR (125 MHz, CDCl3)
d 193.1, 149.6, 134.0, 133.7, 130.0, 128.7,
87.7, 38.9, 33.2, 27.5, 27.4, 25.8; IR (neat): 3308, 3061, 2932, 2854,
2668, 2201, 1966, 1908, 1817, 1777, 1664, 1632, 1596, 1579, 1448,
1311, 1221, 1173, 1022, 982, 824; MS (ESþ) calculated for
[C14H15INaO]þ: 349.0; found: 349.0.
d
7.55–7.51 (m, 9H), 7.48–7.44 (m, 18H), 7.37–7.34 (m, 18H); 13C
NMR (100 MHz, CDCl3)
d
133.9 (d, 3J (13C–31P)¼13.4 Hz), 132.3 (d, 4J
(
(
13C–31P)¼2.9 Hz), 129.4 (d, 2J (13C– 31P)¼11.6 Hz), 128.3 (d, 1J
13C–31P)¼63.5 Hz), 120.3(q, J (13C–19F)¼319.8 Hz); IR (neat): 3055,
2988,
2306,
1422,
1265;
(ESþ)
calculated
for
3.4.18. 3-Bromooct-2-en-4-one (8a)
Yield: 85%. 1H NMR (500 MHz, CDCl3)
d
7.23 (q, 1H, J¼7.0 Hz),
[(Ph3PAu)3O]þ[C54H45Au3OP3]þ: 1393.2, found: 1392, 1409; 31P
NMR (161.9 MHz, CDCl3) d d 81.4.
24.5; 19F NMR (376.2 MHz, CDCl3)
2.77 (t, 2H, J¼7.5 Hz), 2.01 (d, 3H, J¼7.0 Hz), 1.62 (quintet, 2H,
J¼7.5 Hz), 1.35 (sextet, 2H, J¼7.5 Hz), 0.92 (t, 3H, J¼7.5 Hz); 13C NMR
(125 MHz, CDCl3) d 194.3, 139.5, 128.9, 38.4, 26.7, 22.3, 18.2, 13.8; IR
Acknowledgements
(neat): 3042, 2960, 2933, 2873, 1689, 1622, 1466, 1415, 1378, 1288,
1268, 1177, 1154, 1114, 1096, 1075, 972; MS (ESþ) calculated for
[C8H13NaBrO]þ: 227.1; found: 227.0.
This work is supported in part by NSF CAREER award (CHE-
0748484), ACS PRF (43905-G1), ORAU and Merck. The acquisition of
an NMR spectrometer and upgrade of an existing NMR spectro-
meter are funded by NSF CHE-0521191.
3.4.19. 4-Bromo-2,3-dimethylnon-3-en-5-one (8b)
Yield: 93%. E/Z¼1.4:1. 1H NMR (500 MHz, CDCl3) (major isomer):
d
2.99 (septet, 1H, J¼6.5 Hz), 2.75 (t, 2H, J¼7.5 Hz), 1.84 (s, 3H), 1.60
References and notes
(quintet, 2H, J¼7.5 Hz), 1.35 (sextet, 2H, J¼7.5 Hz), 1.03 (d, 6H,
J¼6.5 Hz), 0.92 (t, 3H, J¼7.5 Hz); 1H NMR (minor isomer):
d 3.16
1. For review, see: Negishi, E. J. Organomet. Chem. 1999, 576, 179–194.
2. Kim, K.-M.; Park, I.-H. Synthesis 2004, 2641–2644 and reference therein.
3. (a) Johnson, C. R.; Adams, J. P.; Braun, M. P.; Senanayake, C. B. W.; Wovkulich,
P. M.; Uskokovic, M. R. Tetrahedron Lett. 1992, 33, 917–918; (b) Sha, C. K.; Huang,
S. J. Tetrahedron Lett. 1995, 36, 6927–6928; (c) Djuardi, E.; Bovonsombat, P.;
Nelis, E. M. Synth. Commun. 1997, 27, 2497–2503.
(septet, 1H, J¼7.0 Hz), 2.77 (t, 2H, J¼7.5 Hz), 1.81 (s, 3H), 1.60
(quintet, 2H, J¼7.5 Hz), 1.35 (sextet, 2H, J¼7.5 Hz), 1.03 (d, 6H,
J¼7.0 Hz), 0.92 (t, 3H, J¼7.5 Hz); 13C NMR (mixture of two isomers)
(125 MHz, CDCl3)
d 200.6, 200.5, 148.6, 116.8, 115.3, 41.2, 41.1, 35.1,
4. Krafft, M. E.; Cran, J. W. Synlett 2005, 1263–1266.
32.7, 26.4, 26.3, 22.3, 20.8, 19.5, 17.2, 15.1, 13.9, 13.8; IR (neat): 2962,
2933, 2873, 1690, 1594, 1464, 1407, 1363, 1256, 1232, 1159, 1102,
1061, 987; MS (ESþ) calculated for [C11H19NaBrO]þ: 269.1; found:
269.0.
5. Ref. 4 examined cases of linear enones using a combination of I2 and DMAP.
However, only methyl group at the b-position was shown to lead to good re-
sults. Indeed, in our hands oct-6-en-5-one reacted very sluggishly with only
30% conversion in 2 days.
6. Alimardanov, A.; Negishi, E. Tetrahedron Lett. 1999, 40, 3839–3842.
7. Bellina, F.; Carpita, A.; Ciucci, D.; Desantis, M.; Rossi, R. Tetrahedron 1993, 49,
4677–4698.
3.4.20. 1-Bromo-1-cycloheptylidenehexan-2-one (8c)
8. (a) Bovonsombat, P.; McNelis, E. Tetrahedron Lett. 1993, 34, 8205–8208; (b)
Angara, G. J.; McNelis, E. Tetrahedron Lett. 1991, 32, 2099–2100.
Yield: 95%. 1H NMR (500 MHz, CDCl3)
d
2.77 (t, 2H, J¼7.5 Hz),
2.49 (q, 4H, J¼6.5 Hz), 1.70–1.65 (m, 4H), 1.60 (quintet, 2H,
J¼7.5 Hz), 1.56–1.51 (m, 4H), 1.35 (sextet, 2H, J¼7.5 Hz), 0.92 (t, 3H,
9. For selected reviews on Au/Pt catalysis, see: (a) Hashmi, A. S. K. Chem. Rev. 2007,
107, 3180–3211; (b) Fu¨ rstner, A.; Davis, P. W. Angew. Chem., Int. Ed. 2007, 46,
3410–3449; (c) Gorin, D. J.; Toste, F. D. Nature 2007, 446, 395–403; (d) Patil,
N. T.; Yamamoto, Y. Arkivoc 2007, v, 6–19; (e) Marion, N.; Nolan, S. P. Angew. Chem.,
Int. Ed. 2007, 46, 2750–2752; (f) Jimenez-Nunez, E.; Echavarren, A. M. Chem.
Commun. 2007, 333–346; (g) Zhang, L.; Sun, J.; Kozmin, S. A. Adv. Synth. Catal.
2006, 348, 2271–2296; (h) Ma, S.; Yu, S.; Gu, Z. Angew. Chem., Int. Ed. 2006, 45,
200–203; (i) Widenhoefer, R. A.; Han, X. Eur. J. Org. Chem. 2006, 4555–4563; (j)
Li, Z. G.; Brouwer, C.; He, C. Chem. Rev. 2008, 108, 3239–3265; (k) Arcadi, A.
Chem. Rev. 2008, 108, 3266–3325.
J¼7.5 Hz); 13C NMR (125 MHz, CDCl3)
d 200.1, 150.6, 117.4, 41.2, 37.4,
33.6, 29.1, 28.6, 27.8, 26.4, 25.7, 22.3, 13.9; IR (neat): 2928, 2953,
2858, 2678, 1703, 1688, 1683, 1584, 1464, 1455, 1405, 1379, 1350,
1267, 1244, 1163, 1134, 1084, 1049, 980, 958, 920; MS (ESþ) calcu-
lated for [C13H21NaBrO]þ: 295.1; found: 295.0.
10. For selected examples, see: (a) Miki, K.; Ohe, K.; Uemura, S. J. Org. Chem. 2003,
68, 8505–8513; (b) Mamane, V.; Gress, T.; Krause, H.; Fu¨stner, A. J. Am. Chem.
Soc. 2004, 126, 8654–8655; (c) Shi, X.; Gorin, D. J.; Toste, F. D. J. Am. Chem. Soc.
2005, 127, 5802–5803; (d) Johansson, M. J.; Gorin, D. J.; Staben, S. T.; Toste, F. D.
J. Am. Chem. Soc. 2005, 127, 18002–18003.
11. For the original study, see: Zhang, L. J. Am. Chem. Soc. 2005, 127, 16804–16805.
12. For a computation study on Au catalyzed-transformations of propargylic esters,
see: Correa, A.; Marion, N.; Fensterbank, L.; Malacria, M.; Nolan, S. P.; Cavallo, L.
Angew. Chem., Int. Ed. 2008, 47, 718–721.
3.4.21. 2-Bromo-1-cyclohexyl-2-cyclohexylideneethanone (8d)
Yield: 96%. 1H NMR (500 MHz, CDCl3)
d
3.00 (tt, 1H, J¼11.0,
3.5 Hz), 2.43 (t, 2H, J¼6.0 Hz), 2.28 (t, 2H, J¼5.5 Hz), 1.91–1.88 (m,
2H), 1.79–1.77 (m, 2H), 1.68–1.56 (m, 6H), 1.38–1.18 (m, 6H); 13C
NMR (100 MHz, CDCl3)
d 203.4, 145.9, 112.7, 47.5, 34.4, 32.7, 28.5,
27.9, 27.2, 26.0, 25.8, 25.7; IR (neat): 2931, 2854, 2667, 1689, 1608,
1449, 1365, 1310, 1269, 1242, 1225, 1151, 1120, 1087, 1070, 1045,
1016, 983; MS (ESþ) calculated for [C14H21NaBrO]þ: 307.1; found:
307.2.
13. (a) Zhang, L.; Wang, S. J. Am. Chem. Soc. 2006, 128, 1442–1443; (b) Wang, S. Z.;
Zhang, L. M. J. Am. Chem. Soc. 2006, 128, 8414–8415; (c) Wang, S. Z.; Zhang, L. M.
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1855
Catal. 2007, 349, 871–875; For a related study using PtCl2 as catalyst, see: (e)
Zhang, G.; Catalano, V. J.; Zhang, L. J. Am. Chem. Soc. 2007, 129, 11358–11359.
14. Nolan proposed a different mechanism in their study of enone formation
from propargylic acetates. For reference, see: Marion, N.; Carlqvist, P.; Gea-
lageas, R.; de Fremont, P.; Maseras, F.; Nolan, S. P. Chem.dEur. J. 2007, 13,
6437–6451.
15. For selected later studies from other groups involving Au-catalyzed 3,3-re-
arrangement and/or further activation of the carboxyallene intermediates,
see: (a) Zhao, J.; Hughes, C. O.; Toste, F. D. J. Am. Chem. Soc. 2006, 128, 7436–
7437; (b) Marion, N.; Diez-Gonzalez, S.; de Fremont, P.; Noble, A. R.; Nolan, S.
P. Angew. Chem., Int. Ed. 2006, 45, 3647–3650; (c) Buzas, A.; Gagosz, F. J. Am.
Chem. Soc. 2006, 128, 12614–12615; (d) Buzas, A.; Istrate, F. M.; Gagosz, F. Org.
Lett. 2006, 8, 1957–1959; (e) Oh, C. H.; Kim, A.; Park, W.; Park, D. I.; Kim, N.
Synlett 2006, 2781–2784; (f) Oh, C. H.; Kim, A. New J. Chem. 2007, 31, 1719–
1721; (g) Yeom, H. S.; Yoon, S. J.; Shin, S. Tetrahedron Lett. 2007, 48,
4817–4820; (h) Luo, T.; Schreiber, S. L. Angew. Chem., Int. Ed. 2007, 46,
8250–8253; (i) Sakaguchi, K.; Okada, T.; Shinada, T.; Ohfune, Y. Tetrahedron
Lett. 2008, 49, 25–28.
Sato, T.; Yamamoto, Y. Angew. Chem., Int. Ed. 2006, 45, 4473–4475. (b) Jimenez-
Nunez, E.; Claverie, C. K.; Nieto-Oberhuber, C.; Echavarren, A. M. Angew. Chem.,
Int. Ed. 2006, 45, 5452–5455.
18. A part of this work was previously communicated. For reference, see: Yu, M.;
Zhang, G.; Zhang, L. Org. Lett. 2007, 9, 2147–2150.
19. Iodination of Au–C(sp2) bond generated via other methods by NIS is known
although only a few examples have been reported. For selected references, see:
(a) Buzas, A.; Gagosz, F. Synlett 2006, 2727–2730; (b) Kirsch, S. F.; Binder, J. T.;
Crone, B.; Duschek, A.; Haug, T. T.; Litbert, C.; Menz, H. Angew. Chem., Int. Ed.
2007, 46, 2310–2313; (c) Crone, B.; Kirsch, S. F. J. Org. Chem. 2007, 72, 5435–5438.
20. Mezailles, N.; Ricard, L.; Gagosz, F. Org. Lett. 2005, 7, 4133–4136.
21. Indeed, precipitates, presumably AgI, were observed during the reaction.
Without the addition of AgNTf2, no precipitate forms.
22. The stereoisomers of 6e are inseparable, and the assignment of 1H NMR signals
to the stereoisomers is based on the observation that the Z-isomers in other
cases consistently have chemical shifts at lower fields and further supported by
the NOESY1D of its bromo analog 8b.
23. Nowak, I.; Robins, M. J. J. Org. Chem. 2007, 72, 2678–2681.
24. Greshock, T. J.; Funk, R. L. J. Am. Chem. Soc. 2006, 128, 4946–4947.
25. Ohno, H.; Miyamura, K.; Tanaka, T.; Oishi, S.; Toda, A.; Takemoto, Y.; Fujii, N.;
Ibuka, T. J. Org. Chem. 2002, 67, 1359–1367.
16. For selected examples of Au–C bond nucleophilicity, see: (a) Wei, L.; Li, C. J.
J. Am. Chem. Soc. 2003, 125, 9584–9585; (b) Hashmi, A. S. K.; Frost, T. M.; Bats,
J. W. J. Am. Chem. Soc. 2000, 122, 11553–11554; (c) Shi, Z.; He, C. J. Am. Chem. Soc.
2004, 126, 5964–5965; (d) Dube, P.; Toste, F. D. J. Am. Chem. Soc. 2006, 128,
12062–12063; (e) Wang, S.; Zhang, L. J. Am. Chem. Soc. 2006, 128, 14274–14275;
(f) Buzas, A.; Gagosz, F. Org. Lett. 2006, 8, 515–518; (g) Zhang, G.; Huang, X.; Li,
G.; Zhang, L. J. Am. Chem. Soc. 2008, 130, 1814–1815; (h) Zhang, G. Z.; Zhang, L.
M. J. Am. Chem. Soc. 2008, 130, 12598–12599.
26. Comparing to the average C(sp3)–C(sp2) bond length (1.50 Å), the AuI–C(sp2)
bond is much longer (2.04 Å by averaging eight hits from Cambridge Structural
Database), which may be the reason for the preference for the cis relationship
between Au(PPh3) and R1.
27. Prepared by heating acetate 3e with 10 mol % of AgClO4 in refluxing 2-butanone
for 2 h.
28. Nesmeyanov, A. N.; Perevalova, E. G.; Struchkov, Y. T.; Antipin, M. Y.; Grandberg,
K. I.; Dyadchenko, V. P. J. Organomet. Chem. 1980, 201, 343–349.
17. Alternative to the Au–C(sp2) bond attacking electrophiles directly, electrophilic
reaction with the C–C double bond followed by facile elimination of Au is
possible. For examples with such proposed mechanism, see: (a) Nakamura, I.;