Nitrogen nucleophiles in au-catalyzed dehydrative cyclization reactions

Article abstract of DOI:10.1002/ijch.201300041

Mild conditions for the gold-catalyzed dehydrative cyclization of carbamate-protected azaallylic alcohols to form saturated nitrogen heterocycles are reported. The cyclization reactions are high-yielding, operationally easy to perform, and provide heterocycles with a synthetically useful vinyl group, strategically located on the ring system, which can facilitate further transformations for target oriented synthesis. It is also demonstrated through chirality transfer experiments that the mechanism can be either cationic in nature or a Au-catalyzed addition/elimination sequence. The diverging mechanistic scenario is dependent on the nature of the substituents on the allylic alcohol and necessitates judicious substrate design.

Full text of DOI:10.1002/ijch.201300041

Full Paper
DOI: 10.1002/ijch.201300041
Nitrogen Nucleophiles in Au-Catalyzed Dehydrative
Cyclization Reactions
John M. Ketcham,[a] Flavio S. P. Cardoso,[a] Berenger Biannic,[a] Henri Piras,[a] and Aaron Aponick*[a]
Abstract: Mild conditions for the gold-catalyzed dehydrative
cyclization of carbamate-protected azaallylic alcohols to
form saturated nitrogen heterocycles are reported. The cycli-
zation reactions are high-yielding, operationally easy to per-
form, and provide heterocycles with a synthetically useful
vinyl group, strategically located on the ring system, which
can facilitate further transformations for target oriented syn-
thesis. It is also demonstrated through chirality transfer ex-
periments that the mechanism can be either cationic in
nature or a Au-catalyzed addition/elimination sequence. The
diverging mechanistic scenario is dependent on the nature
of the substituents on the allylic alcohol and necessitates ju-
dicious substrate design.
Keywords: azacycles · dehydrative cyclizations · gold catalysis · heterocycles · SN2’
ic alcohols cyclize more readily than the corresponding
E-allylic alcohols.[3e] Given these difficulties, we focused
our efforts on finding conditions for the formation of pi-
peridines 2 from the challenging carbamate-protected E-
allylic alcohol substrate 1. As was expected, treatment of
1 under our previously reported conditions for tetrahy-
dropyran synthesis resulted in limited conversion to the
desired product (Table 1, entry 1). Use of AuCl, or other
phosphine supported catalysts, was met with similar re-
sults (entries 2–4). Much to our delight, switching to the
catalyst system generated in situ from (IPr)AuCl and
AgBF4 gave the product 2 in 93% yield, after 20 hr at
room temperature, in CH2Cl2, in the presence of molecu-
lar sieves (Table 1, entry 5). Removal of the molecular
sieves from the reaction had little effect on the cycliza-
tion, giving the desired product in 87% yield, and a con-
trol experiment with AgBF4 demonstrated that the cat-
ionic gold complex is indeed needed for the desired reac-
tion (Table 1, entry 8).
Recently, there has been an influx of publications focused
on transition metal-catalyzed allylic alkylation reactions
using unactivated allylic electrophiles.[1] In 2008, our
group reported the first intramolecular gold-catalyzed de-
hydrative cyclization of monoallylic diols, whereby a hy-
droxyl group acts as the formal leaving group.[2] Since
that report, many extensions have been reported by our
group,[3] as well as by many others.[4] With low catalyst
loadings, facile substrate syntheses, and water as the only
by-product, these methods have become powerful tools
for the synthesis of complex heterocycles.
As an extension of our previously reported cyclization
of monoallylic diols, we were interested in utilizing these
cyclization reactions in the formation of nitrogen hetero-
cycles. Recent work from Widenhoefer and co-workers
has established conditions for a gold-catalyzed dehydra-
tive cyclization, using basic nitrogen nucleophiles with
chirality transfer, but these highly coordinating substrates
usually required heating the reaction mixture to 1008C.[4e]
These pivotal reports prompted us to disclose our studies
in this area. At the outset, the goal was to find general
conditions for protected amine substrates, using a simple
Au catalyst, at low temperature, and to study these condi-
tions in chirality transfer reactions of non-racemic azaal-
lylic alcohols. Herein, we report further development of
our previously reported methodology,[2] to include the for-
mation of nitrogen heterocycles, and discuss a surprising
finding regarding the dichotomous nature of the mecha-
nism with different substrates.
It should be noted that no gem-disubstitution is needed
for the reaction to proceed under these conditions. Inter-
estingly, shortening the tether by one methylene unit ap-
pears to influence the reactivity, as revealed by compari-
son of entries 1 in Tables 1 and 2. As can be seen in
Table 2, formation of pyrrolidine 4 from 3 proceeds both
under our previously reported conditions (entry 1) and
[a] J. M. Ketcham, F. S. P. Cardoso, B. Biannic, H. Piras, A. Aponick
Department of Chemistry
University of Florida
Gainesville, FL 32611 (USA)
phone: (+1) 352-392-3484
fax: (+1) 352-846-0296
Although it is preferential to use the more synthetically
versatile carbamate-protected amine substrates, initial ex-
periments from our laboratory demonstrated that sulfona-
mides undergo cyclization much more readily than carba-
mates 1. Furthermore, we have demonstrated that Z-allyl-
e-mail: aponick@chem.ufl.edu
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/ijch.201300041.
Isr. J. Chem. 2013, 53, 923 – 931
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
923

Full Paper
A. Aponick et al.
Table 1. Piperidine optimization studies
Given the ease of hetero-
cycle formation under these
conditions, we set out to
study chirality transfer reac-
tions using the synthesis of
the relatively simple natural Figure 1. Caulophyllumine B
product caulophyllumine B
(Figure 1) as a platform for
entry Au complex
Ag salt solvent yield[a]
1
2
3
4
5
6
7
8
Ph3PAuCl
AuCl
AgOTf
AgOTf
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
<5[b]
9
our initial inquiries. Obtained from the blue cohosh plant,
caulophyllumine B is a small alkaloid that piqued our in-
terested because of its potential biological activity.[5] Al-
though two total syntheses have been reported to date,[6]
the substrate required for piperidine formation using this
method should be readily available and also a good candi-
date for chirality transfer studies.
In a retrosynthetic sense, caulophyllumine B (7) should
easily be prepared from the product of the gold-catalyzed
cyclization of 8 (Scheme 1). We envisioned that 8 could
be easily produced in a few simple steps, starting from
commercially available 5-hexyn-1-ol, and would provide
a short and direct stereoselective synthesis of the precur-
sor to the natural product, using the present methodolo-
gy..
[(o-biphenyl)-di-t-butyl-P]AuCl AgOTf
<5[b]
N.R.
93
(Ph3PAu)3O+BF4
(IPr)AuCl
(IPr)AuCl
(IPr)AuCl
–
–
ꢀ
AgBF4
AgBF4
AgBF4
AgBF4
87[c]
<5[b]
N.R.
CH2Cl2
[a] Purified yields; [b] Conversion determined by 1H NMR
(300 MHz); [c] Molecular sieves omitted.
Table 2. Pyrrolidine optimization studies
The synthesis of the dehydrative cyclization precursor 8
commenced with the preparation of the protected prop-
argyl alcohol 11 (Scheme 2). Treating 9 under the stan-
dard Carreira asymmetric alkynylation conditions,[7] with
the pivaloyl protected 4-hydroxybenzaldehyde, gave the
desired propargyl alcohol 11 in a reasonable yield and
high enantiomeric excess (92% ee). Surprisingly, after
partial hydrogenation under Lindlar conditions and de-
protection of a single Boc group with LiBr, epimerization
of the allylic alcohol stereocenter in 8 was observed.
Since the enantiomeric excess of 8 was already relatively
low, it was essential to find a new substrate that could be
furnished in higher optical purity before cyclization.
To accomplish this goal we turned to a more deactivat-
ing 4-bromo substituent, in hopes of circumventing the
undesired epimerization of the allylic alcohol. Treatment
of alkyne 9 under the standard Carreira alkynylation con-
ditions with 4-bromobenzaldehyde gave the desired prop-
argyl alcohol, 12, in high yield, with 97% ee. Reduction
of the alkyne, followed by partial deprotection of the bis-
carbamate, occurred with only minor epimerization of the
desired substrate 13 and provided a substrate for our chir-
ality transfer studies.[3d,g] Surprisingly, upon treatment of
substrate 13 with the optimized conditions, the product 14
was formed in only one hour, but in an unanticipated
30% ee (Scheme 3). This result was somewhat contrary
to the high chirality transfer observed in the formation of
tetrahydropyrans.[3d,g] It is possible that carbamate-pro-
tected nitrogen nucleophiles function differently than hy-
droxyl groups and basic amines, which have been shown
to transfer the allylic alcohol chirality.[3d,g,4e,k] At the
outset, it was expected that they would behave similarly
and that amine nucleophiles would access a pathway anal-
entry
Au complex
Ag salt
yield[a]
1
2
3
Ph3PAuCl
(IPr)AuCl
[(o-biphenyl)-di-t-butyl-P]AuCl
AgOTf
AgBF4
AgOTf
62
71
<5[b]
[a] Purified yields; [b] Conversion determined by 1H NMR
(300 MHz).
using (IPr)AuCl as the gold salt (entry 2). Since forma-
tion of both pyrrolidines and piperidines proceeded
smoothly using the gold complex formed in situ from
(IPr)AuCl/AgBF4, these conditions were adopted as our
standard conditions.
With the optimized conditions established, the sub-
strate scope was then explored. In order to examine the
role of nitrogen protecting groups, sulfonamides 5a and
5b were employed. These compounds readily cyclized,
with catalyst loadings as low as 1 mol% at room tempera-
ture (Table 3, entries 1–3). When treated under the stan-
dard conditions, E-allylic alcohol 5c gave little conversion
to the desired piperazine 6c; however, Z-allylic alcohol
5d underwent smooth cyclization to give 89% of the
product 6c, after 16 hr at room temperature (Table 3, en-
tries 4 and 5). The method also allows easy access to mor-
pholines, such as 6d, although the cyclization was again
more facile when the Z-allylic alcohol isomer was used
(Table 3, entries 6–8). Lastly, it was found that, while car-
bamates and sulfonamides readily undergo cyclization,
substrates leading to lactams (i.e., 5g!6e) were unreac-
tive, even when higher temperatures and various substitu-
ents in the allylic position were employed.
924
www.ijc.wiley-vch.de
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Isr. J. Chem. 2013, 53, 923 – 931

Au-Catalyzed Cyclization Reactions
Table 3. Scope and limitations
entry
1
substrate
mol (%)
1
time (h)
20
product
yield[a] (%)
71
2
3
2.5
5
6
1
88
92
4
5
16
<20[b]
5
6
5
5
16
24
89
30
7
8
5
5
7
24
51
81
9
5
24
n.r.[b,c]
1
[a] Purified yields; [b] Conversion by H NMR (300 MHz); [c] No reaction.
Scheme 1. Retrosynthetic analysis of caulophyllumine B
ogous to our previously reported transfer of chirality for
monoallylic diols.[3g] In this mechanism (Scheme 4), the
cationic Au catalyst coordinates to the double bond of 13,
forming a p-complex, thereby activating the olefin for nu-
cleophilic attack. This then leads to transition state 15, in
which the hydrogen bonding interaction between the
Scheme 2. Synthesis of substrate 8
Isr. J. Chem. 2013, 53, 923 – 931
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.ijc.wiley-vch.de
925

Full Paper
A. Aponick et al.
would involve ionization of 13 to form the resonance-sta-
bilized cation 17/18 and, after cyclization, 14 with reduced
optical purity (Scheme 5). It is possible that the catalyst
Scheme 3. Chirality transfer with aryl substituents
Scheme 5. Plausible cationic pathway
either directly ionizes the allylic alcohol and is turned
over by loss of water or, alternatively, coordinates to the
carbamate oxygen and acidifies the NH. The fact that 14
is obtained in 30% ee may suggest either that the two
mechanisms are competing or that there is some memory
of chirality with the counterion of 17/18 not being com-
pletely dissociated prior to cyclization.[10]
If electron rich aromatics are required for ionization to
proceed via highly stabilized cations, it may follow that
“non-stabilized” systems would indeed transfer chirality.
To test this theory, we prepared a similar cyclization pre-
cursor, 19, with an alkyl substituent in the allylic position.
Gratifyingly, after treating carbamate 19 with the stan-
dard gold catalysis conditions, chirality transfer was ach-
ieved with only a small loss of enantiomeric excess
(Scheme 6). This result demonstrates the first gold-cata-
Scheme 4. Mechanism of chirality transfer
proton of the carbamate and the oxygen of the allylic al-
cohol should template the reaction, placing the aromatic
group in a pseudo-equatorial position, thereby dictating
the p-facial selectivity. After formation of the s-complex,
the hydroxyl group in 16 is activated by the formation of
an O-H bond and the breaking the N-H bond, but hydro-
gen bonding is likely maintained. The oxonium leaving
group, now perfectly aligned in an anti-periplanar fashion,
allows for the facile dehydration of the allylic system in
16, leading to 14, after loss of water and catalyst turn-
over.
There are a number of possible reasons for such low
optical purity in the recovered product 14, but it would
seem that the most plausible explanation for such a low
transfer of chirality is that inclusion of an aromatic sub-
stituent facilitates a competing pathway involving a Au-
catalyzed ionization of the allylic system and cyclization
of the resulting achiral allylic cation. In this mechanistic
scenario, the Au complex would need to act as a tradition-
al oxophilic Lewis acid,[8] contrary to the now well docu-
mented carbophilic characteristic of Au catalysis.[9] This
Scheme 6. Chirality transfer with alkyl substrates
lyzed transfer of chirality using carbamate-protected ni-
trogen nucleophiles and should be a synthetically useful
tool for the facile synthesis of heterocycles, without the
complications of using a chiral gold complex with
matched and mismatched substrate/catalyst pairs.[11]
Summary and Outlook
The preceding studies with nitrogen nucleophiles have
given valuable insight into the delicate nature of the
926
www.ijc.wiley-vch.de
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Isr. J. Chem. 2013, 53, 923 – 931

Au-Catalyzed Cyclization Reactions
mechanism for gold-catalyzed dehydrative cyclization re-
actions. Substrates with electron rich substituents in the
allylic position can follow a cationic pathway that pro-
vides the product with little transfer of chirality. This
pathway becomes less competitive with substrates bearing
substituents that have reduced electron donating capabili-
ty, thereby giving rise to products with high enantiomeric
excess by an olefin addition/elimination mechanism. Het-
erocycle formation under these conditions presents a mild
and efficient route for the transfer of chirality without the
need for a chiral metal complex and tolerates a broad
range of functional groups. Furthermore, access to carba-
mate synthons via gold catalysis presents a versatile syn-
thetic approach. Use of this method in the synthesis of
complex natural products is underway in our laboratory
and will be reported in due course.
ed as m/e (relative ratio). Accurate masses are reported
for the molecular ion (M+) or a suitable fragment ion.
Example procedure for the optimized gold-catalyzed
dehydrative cyclizations: A test tube with a septum on
top, containing 1,3-bis(2,6-diisopropylphenyl-imidazol-2-
ylidene)gold(I) chloride (6.2 mg, 0.01 mmol, 5 mol%),
silver tetrafluoroborate (1.9 mg, 0.01 mmol, 5 mol%), 4 ꢀ
molecular sieves (MS; previously activated by flame-
drying under vacuum), and a stir bar, was taken from the
glove box wrapped in aluminum foil and placed directly
under dry nitrogen. A small portion of CH2Cl2 (0.2 mL)
was added to the solid catalysts, and the mixture was left
to stir at room temperature for 10 min, after which time
a solution of the substrate (0.2 mmol) in CH2Cl2 (0.8 mL)
was added to the mixture, all at once. The vessel was left
to stir at room temperature. After TLC analysis had
shown complete conversion, the reaction mixture was fil-
tered through a short plug of silica with EtOAc, placed
under vacuum to remove the solvents, and purified by
flash column chromatography.
Selected Experimental Data
General: All reactions were carried out under an atmos-
phere of dry nitrogen, unless otherwise specified. Anhy-
drous solvents were transferred via syringe to flame-dried
glassware, which had been cooled under a stream of dry
nitrogen. Anhydrous tetrahydrofuran (THF) and di-
chloromethane (CH2Cl2) were dried using an MBRAUN
solvent purification system. 5-hexyn-1-ol, 6-chloro-1-
hexyne, and N-(5-hexynyl)phthalimide were graciously
donated to us by Petra Research, Inc. All other reagents
were ordered from Sigma-Aldrich and used without any
further purification. All Au and Ag catalysts were stored
in and transferred to the reaction vessel in a glove box
under a dry argon atmosphere.
Analytical thin layer chromatography (TLC) was per-
formed using 250 mm silica gel 60 ꢀ pre-coated plates
(Whatman Inc.). Flash column chromatography was per-
formed using 230–400 mesh 60 ꢀ silica gel (Whatman
Inc.). The eluents employed are reported as volume:vo-
lume percentages. Proton nuclear magnetic resonance (1H
NMR) spectra were recorded using Varian Unity Inova
500 MHz and Varian Mercury 300 MHz spectrometers.
Chemical shift (d) is reported in parts per million (ppm)
downfield relative to tetramethylsilane (TMS, 0.0 ppm) or
CDCl3 (7.26 ppm). Coupling constants (J) are reported
in Hz. Multiplicities are reported using the following ab-
breviations: s, singlet; d, doublet; t, triplet; q, quartet; m,
multiplet; br, broad. Carbon-13 nuclear magnetic reso-
nance (13C NMR) spectra were recorded using Varian
Unity Mercury 300 and 500 spectrometers at 75 MHz and
125 MHz, respectively. Chemical shift is reported in ppm
relative to the carbon resonance of CDCl3 (77.23 ppm).
Infrared spectra were obtained on a PerkinElmer Spec-
trum RX1 FTIR spectrometer at 1.0 cmꢀ1 resolution and
are reported in wavenumbers. High resolution mass spec-
tra (HRMS) were obtained by the Mass Spectrometry
Core Laboratory of University of Florida, and are report-
(E)-tert-butyl-(7-hydroxy-8-methylnon-5-en-1-yl)carba-
mate (2): Compound 2 was made under the optimized
gold-catalyzed
dehydrative
cyclization
conditions
(Table 1, entry 5), with 1 (39.4 mg, 0.14 mmol), 1,3-
bis(2,6-diisopropylphenyl-imidazol-2-ylidene)gold(I) chlo-
ride (4.7 mg, 0.008 mmol, 5 mol%), silver tetrafluorobo-
rate (1.4 mg, 0.007 mmol, 5 mol%), 4 ꢀ MS, and 1.0 mL
of CH2Cl2. The crude product was purified by flash
column chromatography, using a solvent gradient (5%
EtOAc/hexanes), to yield the product as a clear oil
(34.2 mg, 93%). Rf =0.47 (10% EtOAc/hexanes). IR
1
(neat) 2934, 2862, 1690, 1403, 1363, 1161 cmꢀ1. H NMR
(300 MHz, CDCl3): d 5.48–5.28 (m, 2H), 4.72–4.71 (m,
1H), 3.96–3.84 (m, 1H), 2.81 (td, J=12.8, 3.0 Hz, 1H),
2.28 (dq, J=13.1, 6.6 Hz, 1H), 1.73–1.29 (m, 13H), 0.98
(d, J=6.8, 6H). 13C NMR (75 MHz, CDCl3): d 155.7,
139.1, 125.1, 79.3, 52.2, 39.8, 31.2, 29.7, 28.7, 25.9, 22.8,
22.7, 19.7.
(E)-tert-butyl-(6-hydroxy-7-methyloct-4-en-1-yl)carba-
mate (4): Compound 4 was made under the optimized
gold-catalyzed
(Table 2, entry 2), with 3 (76.8 mg, 0.3 mmol), 1,3-bis(2,6-
diisopropylphenyl-imidazol-2-ylidene)gold(I) chloride
dehydrative
cyclization
conditions
(9.3 mg, 0.015 mmol, 5 mol%), silver tetrafluoroborate
(2.9 mg, 0.015 mmol, 5 mol%), 4 ꢀ MS, and 1.5 mL of
CH2Cl2. The crude product was purified by flash column
chromatography, using a solvent gradient (5% EtOAc/
hexanes), to yield the product as a clear oil (50.6 mg,
71%). Rf =0.70 (20% EtOAc/hexanes). IR (neat) 2958,
2870, 1693, 1390, 1363, 1164, 1115 cmꢀ1. 1H NMR
(300 MHz, CDCl3): d 5.46–5.36 (m, 1H), 5.29–5.20 (m,
1H), 4.16 (br s, 1H), 3.44–3.27 (m, 2H), 2.29–2.20 (m,
1H), 1.96 (br s, 1H), 1.87–1.73 (m, 2H), 1.67–160 (m, 1H),
1.42 (s, 10H), 0.96 (d, J=6.7 Hz, 6H). 13C NMR
(125 MHz, CDCl3): d 154.8, 137.5, 127.7, 79.0, 58.8, 46.3,
32.7, 30.9, 29.9, 28.7, 28.6, 22.8.
Isr. J. Chem. 2013, 53, 923 – 931
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.ijc.wiley-vch.de
927

Full Paper
A. Aponick et al.
(E)-2-(3-methylbut-1-en-1-yl)-1-tosylpyrrolidine (6a)[12]
:
(10.0 mg, 0.016 mmol, 5 mol%), silver tetrafluoroborate
(3.1 mg, 0.016 mmol, 5 mol%), 4 ꢀ MS, and 1.6 mL of
CH2Cl2. The crude product was purified by flash column
Compound 6a was made under the optimized gold-cata-
lyzed dehydrative cyclization conditions (Table 3,
entry 1), with 5a (159.6 mg, 0.5 mmol), 1,3-bis(2,6-diiso-
propylphenyl-imidazol-2-ylidene)gold(I) chloride (3.1 mg,
0.005 mmol, 1 mol%), silver tetrafluoroborate (1.0 mg,
0.005 mmol, 1 mol%), 4 ꢀ MS, and 2.5 mL of CH2Cl2.
The crude product was purified by flash column chroma-
tography, using a solvent gradient (20–50% EtOAc/hex-
anes), to yield the product as a pale yellow oil (106.8 mg,
71%). All data matched that of the previously reported
data.[12]
E)-2-(2-cyclohexylvinyl)-1-tosylpyrrolidine (6b): Com-
pound 6b was made under the optimized gold-catalyzed
dehydrative cyclization conditions (Table 3, entry 2), with
5b (72.8 mg, 0.21 mmol), 1,3-bis(2,6-diisopropylphenyl-
imidazol-2-ylidene)gold(I) chloride (6.4 mg, 0.01 mmol,
5 mol%), silver tetrafluoroborate (2.0 mg, 0.01 mmol,
5 mol%), 4 ꢀ MS, and 1.5 mL of CH2Cl2. The crude
product was purified by flash column chromatography
with a 20% EtOAc/hexanes solution, to yield the product
as a clear oil (64.0 mg, 92%). Rf =0.60 (20% EtOAc/hex-
anes). IR (neat) 3046, 2923, 2850, 1447, 1342, 1156 cmꢀ1.
1H NMR (500 MHz, CDCl3): d 7.70 (d, J=8.2 Hz, 2H),
7.28 (d, J=8.1 Hz, 2H), 5.56 (ddd, J=15.4, 6.4, 1.1 Hz,
1H), 5.27 (ddd, J=15.4, 6.8, 1.4 Hz, 1H), 4.10 (td, J=7.1,
3.9 Hz, 1H), 3.41 (ddd, J=9.7, 7.3, 4.6 Hz, 1H), 3.29 (dt,
J=9.9, 7.1 Hz, 1H), 2.42 (s, 3H), 1.97–1.87 (m, 1H), 1.85–
1.57 (m, 5H), 1.30–1.19 (m, 2H), 1.14 (qt, J=12.6, 3.1 Hz,
1H), 1.08–0.96 (m, 2H). 13C NMR (125 MHz, CDCl3): d
143.2, 137.7, 136.0, 129.6, 127.8, 127.7, 61.9, 48.7, 40.2,
33.0, 32.8, 26.4, 26.2, 26.1, 24.0, 21.7.
chromatography, using
a solvent gradient (10–30%
EtOAc/hexanes), with a 20% EtOAc/hexanes solution, to
yield the product as an off-white solid (75.0 mg, 81%).
Rf =0.85 (60% EtOAc/hexanes). IR (neat) 2975, 2922,
2857, 1699, 1683, 1394, 1168 cmꢀ1. H NMR (500 MHz,
1
CDCl3): d 7.43–7.26 (m, 5H), 5.96–5.90 (m, 1H), 5.87–5.81
(m, 1H), 5.23 (d, J=6.1 Hz, 1H), 4.90 (s, 1H), 4.00 (dt,
J=5.0, 0.9 Hz, 2H), 3.48 (t, J=5.2 Hz, 2H), 3.35–3.19 (m,
2H), 2.25 (s, 1H), 1.44 (s, 10H). 13C NMR (125 MHz,
CDCl3): d 156.2, 142.9, 135.4, 128.8, 128.0, 127.6, 126.5,
79.6, 74.7, 71.1, 69.6, 40.7, 28.7.
N,N-di-tert-butyloxycarbonyl-6-amino-1-hexyne (9): To
a flask containing di-(tert-butyl)-imidodicarbonate (3.1 g,
14.3 mmol, 1.2 eq.), a stir bar, and DMF (25 mL),NaH
(60% in mineral oil, 0.399 g, 14.26 mmol, 1.4 eq.) was
added, portion-wise, at room temperature. The solution
was placed at 608C for 1 hr, then allowed to cool back to
room temperature. The reaction mixture was then added
to a solution of hex-5-yn-1-yl 4-methylbenzenesulfonate[13]
(3.0 g, 11.9 mmol, 1.0 eq.) in DMF (10 mL), at room tem-
perature. After stirring overnight, the reaction was placed
at 08C, quenched with deionized water (100 mL), and ex-
tracted with CH2Cl2 (3ꢁ50 mL). The organic phase was
then dried over MgSO4, filtered, and the solvents were
evaporated under vacuum. The crude product was puri-
fied by flash column chromatography, using a solvent gra-
dient (5–10% EtOAc/hexanes), to yield the product as an
off-white solid (1.41 g, 40%). Rf =0.70 (20% EtOAc/hex-
anes). IR (neat) 2980, 2935, 1744, 1696, 1368, 1139,
1114 cmꢀ1. 1H NMR (300 MHz, CDCl3): d 3.58 (t, J=
6.9 Hz, 2H), 2.22 (dt, J=7.6, 2.7 Hz, 2H), 1.94 (t, J=
2.6 Hz, 1H), 1.75–1.64 (m, 2H), 1.62–1.45 (m, 20H). 13C
NMR (75 MHz, CDCl3): d 152.8, 84.3, 82.3, 68.7, 46.0,
28.4, 28.3, 25.9, 18.4. HRMS (APCI) Calcd for C16H28NO4
(M+H)+: 298.2013; found 298.2000.
(S)-4-7-(N,N-di-tert-butyloxycarbonyl)-1-hydroxyhept-
2-yn-1-yl)phenyl pivalate (11): The following compound
was made using conditions similar to the standard Car-
reira asymmetric alkynylation conditions.[7] To a solution
of Zn(OTf)2 (1.2 g, 3.3 mmol, 1.1 eq.) and (ꢀ)-N-methyle-
phedrine (0.54 g, 3.0 mmol, 1.0 eq.), in toluene (10 mL),
Et3N (0.46 mL, 3.3 mmol, 1.1 eq.) was added, and the so-
lution was left to stir at room temperature for 2 hr, at
which point 9 (892.2 mg, 3.0 mmol, 1.0 eq.), in toluene,
(1 mL) was added to the mixture. The solution was left to
stir for 20 min, and a solution of 4-(pivaloyloxy)benzalde-
hyde[14] (618.7 mg, 3.0 mmol, 1.0 eq.), in toluene, (1.0 mL)
was added. The reaction mixture was left to stir at room
temperature overnight, then quenched with NH4Cl
(30 mL) and extracted with CH2Cl2 (3ꢁ30 mL). The or-
ganic phase was then dried over MgSO4, filtered, and the
solvents were evaporated under vacuum. The crude prod-
uct was purified by flash column chromatography, using
tert-butyl 4-tosyl-2-vinylpiperazine-1-carboxylate (6c):
Compound 6c was made under the optimized gold-cata-
lyzed dehydrative cyclization conditions (Table 3,
entry 5), with 5d (150.3 mg, 0.39 mmol), 1,3-bis(2,6-diiso-
propylphenyl-imidazol-2-ylidene)gold(I)
chloride
(12.1 mg, 0.02 mmol, 5 mol%), silver tetrafluoroborate
(3.8 mg, 0.02 mmol, 5 mol%), 4 ꢀ MS, and 2.0 mL of
CH2Cl2. The crude product was purified by flash column
chromatography, using
a solvent gradient (10–30%
EtOAc/hexanes), with a 20% EtOAc/hexanes solution, to
yield the product as a white solid (127.2 mg, 89%). Rf =
0.80 (60% EtOAc/hexanes). IR (neat) 2976, 2930, 1702,
1455, 1415, 1342, 1159 cmꢀ1. H NMR (500 MHz, CDCl3):
1
d 7.69 (d, J=8.2 Hz, 2H), 7.34–7.26 (m, 2H), 5.70–5.55
(m, 1H), 5.23–5.10 (m, 2H), 4.79–4.68 (m, 2H), 3.81 (s,
2H), 3.47 (s, 2H), 3.32–3.19 (m, 2H), 2.42 (s, 3H), 1.47 (s,
9H). 13C NMR (125 MHz, CDCl3): d 155.4, 154.9, 143.6,
136.8, 133.2, 130.0, 127.5, 119.6, 80.9, 51.9, 46.4, 45.8, 28.6,
21.8.
(E)-tert-butyl 3-styrylmorpholine-4-carboxylate (6d):
Compound 6d was made under the optimized gold-cata-
lyzed dehydrative cyclization conditions (Table 3,
entry 8), with 5f (100.0 mg, 0.32 mmol), 1,3-bis(2,6-diiso-
propylphenyl-imidazol-2-ylidene)gold(I)
chloride
928
www.ijc.wiley-vch.de
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Isr. J. Chem. 2013, 53, 923 – 931

Au-Catalyzed Cyclization Reactions
a solvent gradient (10–25% EtOAc/hexanes), to yield the
product as a translucent pale yellow oil (876.1 mg, 58%).
Rf =0.64 (30% EtOAc/hexanes). IR (neat) 3478, 2978,
2935, 1749, 1694, 1368, 1138, 1116 cmꢀ1. 1H NMR
(300 MHz, CDCl3): d 7.47 (d, J=8.5 Hz, 2H), 6.99 (d, J=
8.5 Hz, 2H), 5.37 (s, 1H), 3.54 (t, 2H), 2.25 (dt, J=7.0,
2.0 Hz, 2H), 1.72–1.57 (m, 2H), 1.57–1.37 (m, 20H), 1.31
(s, 9H). 13C NMR (75 MHz, CDCl3): d 177.1, 152.9, 151.0,
138.9, 127.8, 121.6, 87.0, 82.4, 80.7, 77.43, 64.2, 46.0, 39.2,
28.2, 27.3, 25.7, 18.6. HRMS (ESI) Calcd for
C28H41NNaO7 (M+Na)+: 526.2775; found 526.2792. The
enantiomeric excess (92%) was determined by HPLC
analysis (Chiralpak IB, 5% i-PrOH in hexanes, 1.0 mL/
min, 254 nm), tr 7.7 (minor), 9.2 (major).
Zn(OTf)2 (400.0 mg, 1.1 mmol, 1.1 eq.) and (ꢀ)-N-meth-
ylephedrine (180.0 mg, 1.0 mmol, 1.0 eq.), in toluene
(4 mL), Et3N (0.16 mL, 1.1 mmol, 1.1 eq.) was added, and
the solution as left to stir at room temperature for 2 hr, at
which point 9 (297.4 mg, 1.0 mmol, 1.0 eq.), in toluene
(1 mL), was added to the mixture. The solution was left
to stir for 20 min, and a solution of 4-bromobenzaldehyde
(182.0 mg, 1.0 mmol, 1.0 eq.), in toluene (1.0 mL), was
added. The reaction mixture was left to stir at room tem-
perature overnight, then quenched with NH4Cl (10 mL)
and extracted with CH2Cl2 (3ꢁ10 mL). The organic phase
was then dried over MgSO4, filtered, and the solvents
were evaporated under vacuum. The crude product was
purified by flash column chromatography, using a solvent
gradient (10–25% EtOAc/hexanes), to yield the product
as a colorless oil (366.6 mg, 76%). Rf =0.32 (20%
EtOAc/hexanes). IR (neat) 3464, 2979, 2931, 1729, 1691,
1366, 1134, 1112 cmꢀ1. 1H NMR (300 MHz, CDCl3): d
7.47–7.43 (m, 2H), 7.39–7.35 (m, 2H), 5.38–5.31 (m, 1H),
3.59–3.52 (m, 2H), 2.74–2.70 (m, 1H), 2.29–2.22 (m, 2H),
1.73–1.61 (m, 2H), 1.57–1.41 (m, 20H). 13C NMR
(75 MHz, CDCl3): d 153.0, 140.5, 131.7, 128.5, 122.2, 87.3,
82.5, 80.5, 64.2, 46.0, 28.3, 28.1, 25.6, 18.6. HRMS (APCI)
Calcd for C23H32BrNNaO5 (M+Na)+: 504.1379; found
504.1356. The enantiomeric excess (97%) was determined
by HPLC analysis (Chiralpak IB, 5% i-PrOH in hexanes,
0.8 mL/min, 254 nm), tr 16.4 (major), 17.5 (minor).
(R,Z)-4-(7-((tert-butoxycarbonyl)amino)-1-hydroxy-
hept-2-en-1-yl)phenyl pivalate (8): A two-necked flask
containing 11 (503.6 mg, 1.0 mmol, 1.0 eq.), Lindlarꢂs cat-
alyst (100.0 mg, 20% by wt.), quinoline (100.0 mg, 20%
by wt.), pentane:EtOAc (4.2 mL: 0.42 mL), and a stir bar
was evacuated and backfilled with H2 (g). The solution
was stirred vigorously at room temperature, under the H2
1
(g) atmosphere. The reaction was monitored by H NMR
of small aliquots of the reaction mixture. When the reac-
tion was complete the mixture was filtered through a plug
of cotton with EtOAc to remove the palladium, and the
volatiles were removed under vacuum. The crude materi-
al was sufficient to use in the next step. To a flask con-
taining the crude alkene (from reduction of 11), acetoni-
trile (5 mL), and a stir bar, LiBr (260.5 mg, 3.0 mmol,
3.0 eq.) was added at room temperature. The reaction
mixture was then placed at 658C and left to stir at this
temperature overnight. The reaction mixture was cooled
to room temperature, diluted with EtOAc (30 mL), and
washed with 0.01 M HCl (3ꢁ20 mL). The organic phase
was then dried over MgSO4, filtered, and the solvents
were evaporated under vacuum. The crude product was
purified by flash column chromatography, using a solvent
gradient (5–40% EtOAc/hexanes), to yield the product as
a translucent pale yellow oil (315.9 mg, 78% over 2
steps). Rf =0.15 (30% EtOAc/hexanes). [a]D =ꢀ16.2 (c
1.00, CH2Cl2). IR (neat) 3355, 2931, 1709, 1691, 1681,
1514, 1278, 1172 cmꢀ1. 1H NMR (300 MHz, CDCl3): d
7.38 (d, J=8.5 Hz, 2H), 7.02 (d, J=8.6 Hz, 2H), 5.71–5.45
(m, 3H), 4.66–4.49 (m, 1H), 3.25–2.98 (m, 1H), 2.57–2.45
(m, 1H), 2.40–2.25 (m, 1H), 2.22–2.06 (m, 1H), 1.56–1.37
(m, 14H), 1.35 (s, 9H). 13C NMR (75 MHz, CDCl3): d
177.3, 156.3, 150.4, 141.3, 132.8, 131.6, 127.2, 121.6, 79.4,
69.1, 40.4, 39.2, 29.6, 28.6, 27.3, 27.1, 26.4. HRMS (ESI)
Calcd for C46H70N2NaO10 (2M+Na)+: 833.4923; found
833.4944. The enantiomeric excess (42%) was determined
by HPLC analysis (Chiralpak IB, 10% i-PrOH in hex-
anes, 1.0 mL/min, 254 nm), tr 7.8 (minor), 8.5 (major).
(S)-7-(N,N-di-tert-butyloxycarbonyl)-1-(4-bromophen-
yl)-hept-2-yn-1-ol (12): The following compound was
made using conditions similar to the standard Carreira
asymmetric alkynylation conditions.[7] To a solution of
(R,Z)-tert-butyl (7-(4-bromophenyl)-7-hydroxyhept-5-
en-1-yl)carbamate (13): A two-necked flask containing 12
(366.6 mg, 0.76 mmol, 1.0 eq.), Lindlarꢂs catalyst (73.3 mg,
20% by wt.), quinoline (73.3 mg, 20% by wt.), MeOH
(4 mL), and a stir bar was evacuated and backfilled with
H2 (g). The solution was stirred vigorously at room tem-
perature, under the H2 (g) atmosphere. The reaction was
1
monitored by H NMR of small aliquots of the reaction
mixture. When the reaction was complete, the mixture
was filtered through a plug of cotton with EtOAc to
remove the palladium, and the volatiles were removed
under vacuum. The crude material was sufficient to use in
the next step. To a flask containing the crude alkene
(from reduction of 12), MeOH (5 mL), and a stir bar,
K2CO3 (525.2 mg, 3.8 mmol, 5.0 eq.) was added at room
temperature. The reaction mixture was then placed at
reflux and left to stir overnight. The reaction mixture was
cooled to room temperature, the excess K2CO3 was fil-
tered off, and the solution was placed under vacuum to
remove the MeOH. The crude product was then diluted
with EtOAc (30 mL) and washed with brine (2ꢁ10 mL).
The organic phase was then dried over MgSO4, filtered,
and the solvents were evaporated under vacuum. The
crude product was purified by flash column chromatogra-
phy, using a solvent gradient (0–30% EtOAc/hexanes), to
yield the product as a translucent pale yellow oil
(245.9 mg, 81% over 2 steps). Rf =0.22 (20% EtOAc/hex-
anes). [a]D =ꢀ100.3 (c 1.00, CH2Cl2). IR (neat) 3339,
1
2930, 1687, 1516, 1486, 1169 cmꢀ1. H NMR (300 MHz,
Isr. J. Chem. 2013, 53, 923 – 931
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.ijc.wiley-vch.de
929

Full Paper
A. Aponick et al.
CDCl3): d 7.47–7.41 (m, 2H), 7.28–7.22 (m, 2H), 5.61–5.44
(m, 3H), 4.65–4.45 (m, 1H), 3.24–3.10 (m, 1H), 3.10–2.97
(m, 1H), 2.76 (s, 1H), 2.42–2.23 (m, 1H), 2.20–2.04 (m,
1H), 1.58–1.31 (m, 12H). 13C NMR (75 MHz, CDCl3): d
156.3, 142.9, 132.7, 131.8, 131.7, 127.9, 126.1, 121.3, 79.6,
68.9, 40.3, 29.5, 28.7, 27.0, 26.3. The enantiomeric excess
(91%) was determined by HPLC analysis (Chiralpak IB,
5% i-PrOH in hexanes, 0.8 mL/min, 254 nm), tr 15.9
(major), 20.3 (minor).
(S,E)-tert-butyl-2-(4-bromostyryl)piperidine-1-carboxyl-
ate (14): Compound 14 was made under the optimized
gold-catalyzed dehydrative cyclization conditions with 13
(20.0 mg, 0.05 mmol), 1,3-bis(2,6-diisopropylphenyl-imida-
zol-2-ylidene)gold(I) chloride (1.6 mg, 0.0026 mmol,
5 mol%), silver tetrafluoroborate (0.5 mg, 0.0026 mmol,
5 mol%), 4 ꢀ MS , and 1.0 mL of CH2Cl2. The crude
product was purified by flash column chromatography,
using a solvent gradient (0–5% EtOAc/hexanes), to yield
the product as a clear, colorless oil (16.8 mg, 92%). Rf =
0.56 (20% EtOAc/hexanes). [a]D =ꢀ8.5 (c 1.00, CH2Cl2).
IR (neat) 2935, 2857, 1684, 1486, 1399, 1159 cmꢀ1. 1H
NMR (500 MHz, CDCl3): d 7.45 (d, J=8.5 Hz, 2H), 7.24
(d, J=8.4 Hz, 2H), 6.34 (dd, J=16.2, 1.9 Hz, 1H), 6.20
(dd, J=16.1, 4.8 Hz, 1H), 4.97 (s, 1H), 4.02 (d, J=
13.9 Hz, 2H), 2.91 (td, J=13.0, 2.8 Hz, 1H), 1.88–1.74 (m,
2H), 1.72–1.61 (m, 2H), 1.61–1.37 (m, 9H). 13C NMR
(125 MHz, CDCl3): d 155.6, 136.2, 131.8, 129.9, 129.8,
128.0, 121.3, 79.8, 52.4, 40.2, 29.7, 28.7, 25.7, 19.9. The
enantiomeric excess (30%) was determined by HPLC
analysis (Chiralpak IB, 0.5% i-PrOH in hexanes, 0.8 mL/
min, 254 nm), tr 18.1 (minor), 20.3 (major).
Acknowledgements
We gratefully acknowledge the Herman Frasch Founda-
tion (647-HF07), the donors of the Petroleum Research
Fund (47539-G1), and the James and Esther King Bio-
medical Research Program (09KN-01) for their generous
support of our programs. F.S.P.C. thanks the NSF/
FAPESP US/South America REU program for summer
support. We thank Petra Research, Inc. for the gifts of 5-
hexyn-1-ol, 5-chloro-1-hexyne, N-(5-hexynyl)phthalimide,
and an unrestricted research award.
References
[1] For a recent review on the formation of heterocycles via
metal-catalyzed allylic alkylation reactions see: J. M. Ket-
cham, A. Aponick, Top. Heterocycl. Chem. 2013, 32, 157-
186.
[2] a) A. Aponick, C.-Y. Li, B. Biannic, Org. Lett. 2008, 10,
669–671; b) A. Aponick, B. Biannic, Synthesis 2008, 3356–
3359.
[3] a) A. Aponick, C.-Y. Li, J. A. Palmes, Org. Lett. 2009, 11,
121–124; b) A. Aponick, C.-Y. Li, J. Malinge, E. F. Mar-
ques, Org. Lett. 2009, 11, 4624–4627; c) A. Aponick, B.
Biannic, M. R. Jong, Chem. Commun. 2010, 46, 6849–6851;
d) A. Aponick, B. Biannic, Org. Lett. 2011, 13, 1330–1333;
e) B. Biannic, T. Ghebreghiorgis, A. Aponick, Beilstein J.
Org. Chem. 2011, 7, 802–807; f) B. Biannic, A. Aponick,
Eur. J. Org. Chem. 2011, 6605–6617; g) T. Ghebreghiorgis,
B. Biannic, B. H. Kirk, D. H. Ess, A. Aponick, J. Am. Chem.
Soc. 2012, 134, 16307–16318; h) N. V. Borrero, A. Aponick,
J. Org. Chem. 2012, 77, 8410.
[4] For selected examples see: a) Y. Lu, X. Du, X. Jia, Y. Liu,
Adv. Synth. Catal. 2009, 351, 1517–1522; b) M. Bandini, M.
Monari, A. Romaniello, M. Tragni, Chem. Eur. J. 2010, 16,
14272–14277; c) W. P. Unsworth, K. Stevens, S. G. Lamont,
J. Robertson, Chem. Commun. 2011, 47, 7659–7661; d) M.
Chiarucci, M. Lorcritani, G. Cera, M. Bandini, Beilstein J.
Org. Chem. 2011, 7, 1198–1204; e) P. Mukherjee, R. A. Wi-
denhoefer, Org. Lett. 2011, 13, 1334–1337; f) P. Mukherjee,
R. A. Widenhoefer, Angew. Chem. Int. Ed. 2012, 51, 1405–
1407; g) M. Chiarucci, M. di Lillo, A. Romaniello, P. G.
Cozzi, G. Cera, M. Bandini, Chem. Sci. 2012, 3, 2859–2863;
h) M. Bandini, A. Bottoni, M. Chiarucci, G. Cera, G. P. Mis-
cione, J. Am. Chem. Soc. 2012, 134, 20690–20700; i) C. F.
Xu, M. Xu, L.-Q. Yang, C.-Y. Li, J. Org. Chem. 2012, 77,
3010; j) P. C. Young, N. A. Schopf, A.-L. Lee, Chem
Commun. 2013, 49, 4262–4264; k) P. Mukherjee, R. A. Wi-
denhoefer, Chem. Eur. J. 2013, 19, 3437–3444.
[5] a) Z. Ali, Z. A. Khan, Phytochemistry 2008, 69, 1037–1042;
b) V. L. M. Madgula, Z. Ali, T. Smillie, I. A. Khan, L. A.
Walker, S. I. Khan, Planta Med. 2009, 75, 329–332; c) Y.
Hu, I. A. Khan, A. K. Dasmahapatra, Planta Med. 2009, 75,
399–457.
[6] a) P. R. Krishna, B. K. Reddy, Tetrahedron Lett. 2010, 51,
6262–6264; b) A. Khanna, C. Maung, K. R. Johnson, T. T.
Luong, D. L. Van Vranken, Org. Lett. 2012, 14, 3233–3235.
[7] D. E. Frantz, R. Fassler, E. M. Carreira, J. Am. Chem. Soc.
1999, 121, 11245–11246.
(R,E)-tert-butyl 2-(4-phenylbut-1-en-1-yl)piperidine-1-
carboxylate (20): The following compound was made
under the optimized gold-catalyzed dehydrative cycliza-
tion conditions with 19 (13.0 mg, 0.04 mmol), 1,3-bis(2,6-
diisopropylphenyl-imidazol-2-ylidene)gold(I)
chloride
(2.4 mg, 0.004 mmol, 10 mol%), silver tetrafluoroborate
(0.8 mg, 0.004 mmol, 10 mol%), 4 ꢀ MS, and 1.0 mL of
CH2Cl2, at 408C. The crude product was purified by flash
column chromatography, using a solvent gradient (0–5%
EtOAc/hexanes), to yield the product as a white solid
(10.4 mg, 87%). Rf =0.62 (20% EtOAc/hexanes). [a]D =
30.1 (c=0.70, CH2Cl2). IR (neat) 2931, 2857, 1687, 1407,
1
1363, 1159 cmꢀ1. H NMR (300 MHz, CDCl3): d 7.29–7.25
(m, 2H), 7.20–7.15 (m, 3H), 5.48 (dtd, J=15.1, 6.6, 1.7 Hz,
1H), 5.41–5.35 (m, 1H), 4.72 (s, 1H), 3.88 (d, J=13.5 Hz,
1H), 2.78–2.66 (m, 3H), 2.39–2.33 (m, 2H), 1.66–1.61 (m,
2H), 1.58–1.50 (m, 3H), 1.45 (s, 9H), 1.42- 1.33 (m, 1H).
13C NMR (125 MHz, CDCl3): d 155.6, 142.0, 130.9, 129.4,
128.7, 128.5, 126.0, 79.4, 52.0, 39.8, 36.0, 34.5, 29.6, 28.7,
25.8, 19.6. The enantiomeric excess (92%) was deter-
mined by HPLC analysis (Chiralcel OJ-H, 1.0% i-PrOH
in hexanes, 1.0 mL/min, 215 nm), tr 8.8 (major), 13.2
(minor).
[8] For selected recent reports on the oxophilic nature of gold
complexes, see: a) H.-Q. Xiao, X.-Z. Shu, K.-G. Ji, C.-Z. Qi,
930
www.ijc.wiley-vch.de
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Isr. J. Chem. 2013, 53, 923 – 931

Au-Catalyzed Cyclization Reactions
Y.-M. Liang, Catal. Commun. 2009, 10, 1824; b) A. R. Jag-
dale, S. W. Youn, Eur. J. Org. Chem. 2011, 3904–3910;
c) D. V. Vidhani, J. W. Cran, M. E. Krafft, M. Manoharan,
I. V. Alabugin, J. Org. Chem. 2013, 78, 2059–2073.
Fuji, Top. Stereochem. 2003, 23, 175; c) H. Zhao, D. C. Hsu,
P. R. Carlier, Synthesis 2005, 1.
[11] Gold-catalyzed transfer of chirality with a carbamate has
been previously reported using a chiral gold complex. See
reference [4f].
[12] Q. Shuifa, L. Guosheng, W. Yunyang, Chem. Eur. J. 2009,
15, 2751–2754.
[13] O. A. Battenberg, M. B. Nodwell, S. A. Sieber, J. Org.
[9] The carbophilic nature of gold complexes is well accepted
and has been exploited in various methods. For reviews see:
a) A. S. K. Hashmi, Chem. Rev. 2007, 107, 3180–3211;
b) D. J. Gorin, B. D. Sherry, F. D. Toste, Chem. Rev. 2008,
108, 3351–3378; c) F. Dꢃnꢄs, A. Pꢃrez-Luna, F. Chemla,
Chem. Rev. 2010, 110, 2366–2447; d) A. Corma, A. Leyva-
Perez, M. J. Sabater, Chem. Rev. 2011, 111, 1657.
Chem. 2009, 74, 4143–4148.
[14] C. S. Stauffer, P. Bhaket, A. W. Fothergill, M. G. Rinaldi, A.
Datta, J. Org. Chem. 2007, 72, 9991–9997.
[10] For a recent review on the memory of chirality in gold-cata-
lyzed transformations, see: a) N. T. Patil, Chem. Asian. J.
2012, 7, 2186–2194. For selected reviews on the memory of
chirality in asymmetric synthesis, see: b) T. Kawabata, K.
Received: April 13, 2013
Accepted: June 13, 2013
Published online: August 23, 2013
Isr. J. Chem. 2013, 53, 923 – 931
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.ijc.wiley-vch.de
931