Towards asymmetric Au-catalyzed hydroxy- and alkoxycyclization of 1,6-enynes

Article abstract of DOI:10.1016/j.jorganchem.2008.08.008

The efficiency of a Au(III)/chiral ligand system has been studied. The association of several chiral mono- and bidentate phosphanes with gold has been tested in the formal addition of an oxygen nucleophile to an alkene followed by a cyclization process, n

Full text of DOI:10.1016/j.jorganchem.2008.08.008

Journal of Organometallic Chemistry 694 (2009) 538–545
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Towards asymmetric Au-catalyzed hydroxy- and alkoxycyclization of 1,6-enynes
*
Chung-Meng Chao, Emilie Genin, Patrick Y. Toullec, Jean-Pierre Genêt, Véronique Michelet
Laboratoire de Synthèse Sélective Organique et Produits Naturels, E.N.S.C.P., UMR 7573, 11 rue P. et M. Curie, F-75231 Paris Cedex 05, France
a r t i c l e i n f o
a b s t r a c t
Article history:
The efficiency of a Au(III)/chiral ligand system has been studied. The association of several chiral mono-
and bidentate phosphanes with gold has been tested in the formal addition of an oxygen nucleophile to
an alkene followed by a cyclization process, namely the hydroxycyclization reaction of 1,6-enynes. The
use of (R)-4-MeO-3,5-(t-Bu)2-MeOBIPHEP ligand led to clean cycloisomerizations and afforded the high-
est enantiomeric excesses. The enantiomeric excesses were highly dependant on the substrate/nucleo-
phile combination. A 31P NMR study of the catalytic species tends to prove that Au(III) catalyst may be
reduced to Au(I) intermediate in the presence of phosphanes.
Received 10 July 2008
Accepted 4 August 2008
Available online 11 August 2008
Keywords:
Gold
Enynes
Asymmetric catalysis
Cycloisomerization
Tandem reactions
Ó 2008 Elsevier B.V. All rights reserved.
1. Introduction
(Scheme 2) [7]. These reactions offer the unique opportunity to
create two bonds in a diastereoselective manner. They are based
Recent years have witnessed a substantial growth in the num-
ber of gold-catalyzed reactions implying C–C, C–O or C–N bond for-
mation processes [1]. Despite the rapid development of several
synthetic applications, the stereoselective aspects still require
investigations and have been scarcely studied [2]. The first report
of a gold-catalyzed enantioselective transformation dates from
1986 when Hayashi and Ito described the aldol condensation be-
tween isocyanates and aldehydes in the presence of a chiral ferr-
ocenyl-based diphosphane–Au(I) complex [3]. In line with the
increasing interest associated with the carbophilic Lewis acid prop-
erties of gold complexes, a number of publications describing the
asymmetric hydroalkoxylation, hydroamination and hydroaryla-
tion of allenes, [2+2] cycloaddition and cycloisomerization of enal-
lenes [2] have recently appeared. Whereas most of these studies
deal with the activation of allenes towards nucleophilic attack,
only two reports addressed the asymmetric activation of sub-
strates containing an alkyne function (Scheme 1). In 2005, Echavar-
ren et al. synthesized a variety of Au(I)–phosphanes complexes and
applied those catalyst to the alkoxycyclization of 1,6-enynes [4a].
The same year, the group of Toste reported the gold-catalyzed
cyclopropanation of styrenes with enantioselectivities up to 94%
ee [4b].
on the hypothesis of a common cyclopropylcarbene intermediate
[7m,8], which would be attacked by a nucleophile to give the de-
sired alcohol or ether after rearrangement. To the best of our
knowledge, there is only a unique report concerning the asymmet-
ric alkoxycyclization (5 examples) and leading to moderate
(ee = 2–53%) and excellent (ee = 94% in a single case, Scheme 1)
enantioselection [4a]. In pursuit of the investigation on atom-eco-
nomical metal-catalyzed cycloisomerization reactions, [9] we have
envisaged to study the asymmetric gold-catalyzed tandem C–C/C–
O bond process. We wish therefore to present in this paper our pre-
liminary results leading to enantiomerically enriched functional-
ized cyclic alkenes starting from 1,6-enynes.
2. Results and discussion
2.1. Optimization of the catalyst system
Initial efforts have focused on the optimization of an efficient
system starting from enyne 1a as a model substrate. We investi-
gated Au(I) and Au(III) catalysts associated with the atropisomeric
ligand (R)-MeOBIPHEP [10] and first studied the influence of silver
salts (Table 1). The absolute configuration of the resulting alcohol
was determined based on our studies in the presence of chiral plat-
inum complexes [7b]. The use of AuCl or AuCl3 showed an evident
higher efficiency of Au(III) catalyst. The desired alcohol was ob-
tained in a better yield and enantiomeric excess (Table 1, entries
1–2). The influence of silver salts (Table 1, entries 3–5) did not lead
to significant modifications as the enantiomeric excesses were
determined around 50%. Lowering the catalytic loading of silver
In the course of our ongoing research on metal-catalyzed cyclo-
isomerization reactions of enynes, which are one of the best atom-
economical ways for sustainability [5,6], we and others have
described novel rearrangements in the presence of external nucle-
ophiles such as alcohols, electron-rich aromatic rings and amines
* Corresponding author. Tel.: +33 144276742; fax: +33 144071062.
E-mail address: veronique-michelet@enscp.fr (V. Michelet).
0022-328X/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2008.08.008

C.-M. Chao et al. / Journal of Organometallic Chemistry 694 (2009) 538–545
539
1.6 mol%
OMe
(R)-TolBINAP(AuCl)
2
PhO S
PhO S
2
*
2
2 mol% AgSbF
6
Ph
Ph
PhO S
PhO S
2
2
MeOH (10 equiv.), 168 h
CH Cl 24°C
2
2,
(-)
52%, 94% ee
2.5 mol%
(R)-DTBM-SEGPHOS(AuCl)
2
OPiv
5 mol% AgSbF
6
+
OPiv
MeNO rt, > 20:1 cis:trans
2,
71%, 94% ee
Scheme 1. Asymmetric gold-catalyzed reactions.
the hydroxycyclization reaction but did not dramatically modify
the enantiomeric excesses (Table 1, entries 7–8). A better repro-
ducibility was obtained in the presence of a Au/Ag ratio of 1/3.
The use of a higher Au/ligand catalyst ratio (1:1) was also investi-
gated without further improvement (Table 1, entry 9). Further
studies implying a different cosolvent or various concentrations
did not give better results.
We further pursued our study under the following conditions:
10 mol% of AuCl3, 30 mol% AgSbF6 and 5 mol% ligand at room tem-
perature. We next studied the influence of the chiral ligand on the
enantiodiscrimination of the reaction. Few reports were published
when we started this work and no enantioselective systems were
based on Au(III) precursor. The use of TolBINAP [4a,11] afforded
the desired alcohol in a moderate 22% enantiomeric excess (Table
2, entry 1). We investigated the influence of other bidentate phos-
phorus-based architectures such as the C2-symmetric (+)-BIPNOR
[12] (Table 2, entry 2) or planar chiral diphosphanes ((R,S)-Josiphos
and (R)-(S)-PPF-PtBu2 [13], (Table 2, entries 3–4), the latter one
showing an interesting activity. The use of atropisomeric mono-
phosphanes such as (S)-MeO-MOP [14], (R)-BINAPO [15] did not
give better results (Table 2, entries 5–6).
OR
H
R2
R1
Z
ROH
H
NHR
R2
H
R2
R1
R2
[Au]
RNH2
Z
Z
R1
R1
Z
[Au]
Ar
H
R2
ArH
R1
Z
Scheme 2. Cycloisomerization reactions of enynes in the presence of various
nucleophiles.
salts to 5 mol% considerably diminished the kinetic of the reaction
(168 h instead of 1 h) and induced a large decrease in enantiomeric
excess (Table 1, entry 6). Increasing the [Ag]/[Au] ratio accelerated
Table 1
Optimization of the gold catalytic system
[Au] (10 mol%)
[Ag] (x mol%)
OH
MeO
MeO
PPh
PPh
H
2
2
(R)-MeOBIPHEP
MeO C
MeO C
2
2
(5 mol%)
Ph
Ph
dioxane/H O (6/1)
2
MeO C
2
MeO C
2
rt, 1-168 h
(-)-2a
1a
(R)-MeOBIPHEP
Entry
[Au] catalyst
[Ag] salts (mol%)
Yielda (%)
ee (%)b
1
2
3
4
5
6
7
8
9d
AuCl
AgSbF6 (10)
AgSbF6 (30)
AgBF4 (30)
AgPF6 (30)
AgAsF6 (30)
AgSbF6 (5)
AgSbF6 (10)
AgSbF6 (15)
AgSbF6 (30)
44c
83
92
99
94
29
59
54
51
53
12
53
55
51
AuCl3
AuCl3
AuCl3
AuCl3
AuCl3
AuCl3
AuCl3
AuCl3
57c
100c
100c
95
a
Isolated yield.
Measured by HPLC.
Conversion.
b
c
d
10 mol% (R)-MeOBIPHEP.

540
C.-M. Chao et al. / Journal of Organometallic Chemistry 694 (2009) 538–545
Table 2
Ligand screening for the asymmetric hydroxycyclization reaction
AuCl3 (10 mol%)
AgSbF6 (30 mol%)
chiral ligand (5 mol%)
OH
OH
H
H
MeO2C
MeO2C
MeO2C
MeO2C
MeO2C
MeO2C
Ph
Ph
Ph
or
dioxane/H2O (6/1)
rt
(+)-2a
(-)-2a
1a
Entry
Chiral ligand
t (h)
Yielda (%)
ee (%) (config.)b
1
2
3
(R)-TolBINAP
(+)-BIPNOR
(R,S)-Josiphos
(R)-(S)-PPF-PtBu2
(S)-MeO-MOP
(R)-BINAPO
(R)-Ph-BINEPINE
(R)-(2-furyl)-MeOBIPHEP
(S)-p-Tol-MeOBIPHEP
(S)-(4-NMe2)-MeOBIPHEP
(R)-3,5-Me-MeOBIPHEP
(R)-3,5-iPr-MeOBIPHEP
(R)-3,5-tBu-4-MeO-MeOBIPHEP
(R)-Cy-MeOBIPHEP
72
21
36
19
20
20
20
17
156
60
19
19
17
18
18
17
86
99
90
96
99
99
0
86
22 (ꢀ)
9 (+)
26 (ꢀ)
49 (ꢀ)
4 (ꢀ)
38 (ꢀ)
/
4
5c
6
7c,d
8
0
9
31e
100e
89
14 (+)
41 (+)
22 (ꢀ)
33 (ꢀ)
72 (ꢀ)
4 (ꢀ)
8 (+)
10
11
12
13
14
15
16
96
98
100e
100e
99
(S)-iPr-MeOBIPHEP
(R)-3,5-tBu-4-MeO-SEGPHOS
63 (ꢀ)
a
Isolated yield.
Measured by HPLC.
10 mol%.
60 °C.
Conversion.
b
c
d
e
Ph
Ph
MeO
MeO
PPh2
PPh2
PAr2
PAr2
P
Ph
P
P
Ph
Ph
(+)-BIPNOR
Ar = p-Me-C6H4, (R)-TolBINAP
(R)-MeOBIPHEP
(R)-Ph-BINEPINE
O
PR'2
PPh2
O
PPh2
PPh2
PR2
Fe
R = C6H5, R' = C6H11, (R,S)-Josiphos
R = C6H5, R' = C(CH3)3, (R,S)-PPF-PtBu2
(S)-MeO-MOP
(R)-BINAPO
MeO
MeO
PAr2
PAr2
MeO
MeO
PAr2
PAr2
Ar = 4-Me2N-C6H4
Ar = phenyl, (R)-MeOBIPHEP
(S)-(4-NMe2)-MeOBIPHEP
Ar = 4-Me-C6H4
(S)-p-Tol-MeOBIPHEP
Ar = furyl, (R)-(2-furyl)-MeOBIPHEP
Ar = 3,5-t-Bu-4-MeO-C6H2, (R)-(3,5-t-Bu-4-MeO)-MeOBIPHEP
Ar = 3,5-Me-C6H3, (R)-(3,5-Me)-MeOBIPHEP
Ar = 3,5-iPr-C6H3, (R)-(3,5-i-Pr)-MeOBIPHEP
O
O
O
PAr2
PAr2
MeO
MeO
PR2
PR2
O
Ar = 3,5-t-Bu-4-MeO-C6H2,
(R)-(3,5-t-Bu-4-MeO)-SEGPHOS
R = Cy, (R)-Cy-MeOBIPHEP
R = iPr, (R)-i-Pr-MeOBIPHEP

C.-M. Chao et al. / Journal of Organometallic Chemistry 694 (2009) 538–545
541
Table 3
Asymmetric gold-catalyzed hydroxy- and alkoxycyclization reactions of 1,6-enynes
10 mol% AuCl
30 mol% AgSbF
5 mol% L*
3
1
MeO
MeO
PAr2
PAr2
OR
R
6
H
1
R
2
R
2
R
Z
Z
solvent
rt - 40°C
Ar = 3,5-t-Bu-4-MeO-C H
6
2
(R)-(3,5-t-Bu-4-MeO)-MeOBIPHEP
Entry
1
1,6-Enyne
MeO2C
Solvent
MeOH
t (h)
Product
Yielda (%)
99
ee (%) (config.)b
30 (ꢀ)
48
OMe
H
Ph
MeO2C
Ph
MeO2C
1a
1a
1a
MeO2C
2b
MeO2C
MeO2C
OEt
H
Ph
Ph
2
3
EtOH
18
18
88
89
55 (ꢀ)
62 (ꢀ)
MeO2C
Ph
MeO2C
2c
MeO2C
MeO2C
O
H
C3H5OH
MeO2C
Ph
MeO2C
2d
OH
H
4
5
Dioxane/eau (6/1)
MeOH
96
19
66
99
24 (ꢀ)
30 (ꢀ)
MeO2C
MeO2C
MeO2C
MeO2C
3a
1b
OMe
H
MeO2C
MeO2C
MeO2C
MeO2C
3b
1b
PhO S
2
OMe
H
Ph
6c
7c
8
MeOH
72
72
24
24
99
82
99
99
53 (ꢀ)
71 (ꢀ)
72 (ꢀ)
78 (ꢀ)
PhO2S
Ph
PhO S
2
4a
4a
PhO2S
5b
PhO S
2
OEt
H
Ph
EtOH
PhO2S
Ph
PhO S
2
PhO2S
5c
OH
H
PhO S
2
Dioxane/eau (6/1)
PhO S
2
PhO S
2
4b
4b
PhO S
2
6a
OEt
H
PhO S
2
9
EtOH
PhO2S
PhO2S
PhO S
2
6c
OH
O
H
O
10
Dioxane/eau (6/1)
MeOH
22
26
72
65
56
99
37 (ꢀ)
33 (ꢀ)
32 (ꢀ)
O
O 7a
O
O
O
8a
8b
OMe
O
H
O
11
12c
O
O
O 7a
OH
Ph
H
TsN
Dioxane/eau (6/1)
Ph
9a
TsN
10a
a
Isolated yield.
Measured by HPLC.
Reaction at 40 °C.
b
c

542
C.-M. Chao et al. / Journal of Organometallic Chemistry 694 (2009) 538–545
The case of (R)-Ph-BINEPINE [16,17], known as an excellent chiral
promoter in the presence of platinum [7b], was particularly sur-
prising as the ligand completely inhibited the reaction (Table 2, en-
try 7) either at room temperature or at 60 °C. We therefore,
decided to screen a set of chiral atropisomeric ligands displaying
different stereoelectronic properties. A combination of gold and
electron-poor analogue of MeOBIPHEP ligand (Table 2, entry 8)
led to the desired alcohol in good yield but in a racemic form.
The use of electron-rich analogues of MeOBIPHEP such as (S)-p-
Tol-MeOBIPHEP and (S)-(4-NMe2)-MeOBIPHEP enhanced the
enantioselection of the reaction leading to 41% ee in the latter case
(Table 2, entries 9–10). The influence of steric factors was also ob-
served when performing the reaction in the presence of 3,5-disub-
stituted MeOBIPHEP analogues (Table 2, entries 11–12). When
combining both effects by using (R)-3,5-t-Bu-4-MeO-MeOBIPHEP
ligand, the enantiomeric excess reached 72% (Table 2, entry 13).
Further studies with alkyl-substituted ligands (Table 2, entries
14-15) or benzodioxolane-substituted ligand [18] (Table 2, entry
16) did not allow us to obtain better enantiomeric excesses. It is
noteworthy that the DTBM-SEGPHOS ligand, known as an excellent
chiral promoter in gold catalysis [2], unfortunately did not afford
higher enantiomeric excess than 63% (Table 2, entry 16).
surprised to obtain lower enantiomeric excesses. The hydroxy-
and methoxycyclization reactions of enynes 7a and 9a led to the
alcohols 8a, 10a and ether 8b in modest 32–37% enantiomeric
excesses.
2.3. Mechanistic considerations
An initial complexation of the carbophilic Lewis acid cationic
gold catalyst to the alkyne function allows the formation of tran-
sient unstable cyclopropylcarbenes [7m,8,20] B and B0 via stereose-
lective attack of the alkene function on the alkyne (Scheme 3).
These two intermediates are diastereomers and virtually in equi-
librium via the starting
g
2-complex A. We may postulate the exis-
tence of an equilibrium between complexes A and B to explain the
variation of enantioselectivity observed for a given enyne substrate
and different oxygen nucleophiles. Indeed, considering the anti
nucleophilic attack on the cyclopropylcarbene intermediates B/B0
as a stereospecific event, the external oxygen nucleophile does
not take part in the cyclopropylcarbene formation which therefore
represents the enantiodetermining step of this transformation. It is
noteworthy that a concerted mechanism based on the addition/
cyclization (direct transformation of intermediate A to C and C0)
cannot be ruled out and would explain also the influence of the
nucleophile on the observed enantioselectivities. Addition of the
external nucleophile releases two vinylaurate intermediates C
and C0. Protodemetalation completes the catalytic cycle and affords
2 as an enantiomeric mixture.
In order to get insight into the catalytically active species, we
got engaged in a 31P NMR study of the gold complexes formed un-
der our reaction conditions. As a model catalyst, we first investi-
gated the combination of AuCl3, PPh3 and 3 equiv. of AgSbF6. In a
first step, AuCl3 and PPh3 were mixed in CDCl3. Two phosphorus-
containing products were formed in a 1:1 ratio upon mixing for
30 min (Scheme 4, Fig. 1). On the basis of their 31P NMR shifts
[21,22], they were respectively, assigned as PPh3AuCl
(d = +33.3 ppm) and Ph3P(O) ꢁ HCl (d = +42.5 ppm) [23]. This reac-
tivity can be explained on the basis of an oxidoreduction process
involving PPh3 as a reducing agent. In an initial step, one equiva-
lent of AuCl3 and one equivalent of PPh3 are converted into AuCl
and Ph3PCl2. AuCl is then complexed by a second equivalent of
PPh3 to form PPh3AuCl, whereas Ph3PCl2 reacts with traces of water
to form PPh3P(O) and 2 equiv. of HCl. [24] This process is reminis-
cent to the synthesis of (tht)AuCl involving the reaction of HAuCl4
The best candidate was therefore the atropisomeric electron-
rich and sterically hindered (R)-3,5-t-Bu-4-MeO-MeOBIPHEP li-
gand. We performed several other modifications of the reaction
conditions (temperature, cosolvents) without success. Having in
hand an optimized Au(III)/Ag/chiral ligand system, we then
decided to evaluate the scope and limitations on various 1,6-eny-
nes and in the presence of alcohols such as methanol, ethanol
and allylic alcohol.
2.2. Scope and limitations
Several carbon-, oxygen- or nitrogen-tethered 1,6-enynes were
prepared according to classic and described alkylation reaction
procedures [7]. They were then subjected to the catalytic system
implying 10 mol% of AuCl3, 30 mol% of AgSbF6 and 5 mol% of (R)-
3,5-t-Bu-4-MeO-MeOBIPHEP ligand (Table 3).
The influence of the external oxygen nucleophile on the enan-
tiomeric excesses was readily observed. The addition of methanol,
leading to the ether 2b (Table 3, entry 1) induced a decrease of the
enantiomeric excess (30%), even though the reaction was extre-
mely performant. The use of ethanol and allylic alcohol gave better
enantiomeric excesses (Table 3, entries 2–3) as the corresponding
ethers were isolated in good yields and with respectively, 52%
and 62% enantiomeric excesses. The challenging case of 1,6-enyne
1b was then investigated. The addition of water afforded the alco-
hol 3a in a modest 24% ee (Table 3, entry 4), whereas the use of
methanol allowed the formation of the ether 3b with 30% enantio-
meric excess (Table 3, entry 5). It is noteworthy that the control of
a unique stereocenter had already been studied in the presence of a
Au(I) catalyst [4a] and led to the methyl ether in 2% enantiomeric
excess. Anticipating that the carbon-tethered link might also influ-
enced the enantioselection of the reaction, we then tested the
cycloisomerization of a bis-sulfonyl-substituted derivative 4a. In-
deed, we were pleased to find that the catalytic system was actu-
ally more efficient as the corresponding methyl and ethyl ethers
were respectively obtained in 53% and 71% enantiomeric excesses
(Table 3, entries 6–7). Changing the alkenyl side chain still allowed
the formation of the desired alcohol 6a and ether 6c in excellent
yields (Table 3, entries 8–9) and good enantiomeric excesses
(72% and 78%, respectively). In all carbon-tethered enynes, the
enantiomeric excesses increased going from methanol to ethanol
as a nucleophile. The unexplored case of oxygen- and nitrogen con-
taining enynes was also investigated. Considering the potential
weaker Thorpe-Ingold effect [19] of such substrates, we were not
R1
Nu
Nu
H
H
R1
R2
R1
R2
R2
+
Z
Z
[Au]+
Z
H
H+
R1
Nu
Nu
R2
H
H
R1
R2
R1
R2
H+
Nu-H
+
Z
Z
Z
H
[Au]
[Au]
C
C'
[Au]+
A
H
H+
R2
R1
Z
Nu-H
[Au]+
H
B
R1
R2
+
Z
[Au+]
B'
Scheme 3. Proposed mechanism for the hydroxy- and alkoxycyclization reactions.

C.-M. Chao et al. / Journal of Organometallic Chemistry 694 (2009) 538–545
543
Ph PCl
+
+
AuCl
PPh
AuCl
3
2
3
3
PPh
H O
- HCl
2
3
PPh AuCl
Ph P(O).HCl
3
3
31
31
(
P) = + 33.3 ppm
( P) = + 42.5 ppm
δ
δ
Scheme 4. Proposed catalytic gold species for a AuCl3/PPh3 mixture.
Fig. 2. 13P NMR spectrum for AuCl3/(R)-MeOBIPHEP (1/0.5) mixture.
nally, whereas the catalytic active species turned to be the same
with both systems, the superior activity observed with the Au(III)
precursors versus Au(I) (Table 1, entries 1 and 2) may probably
be explained on the basis of Brønsted acid cocatalysis [29], the cat-
alytic amount of HCl produced during the Au(III)/Au(I) reduction
process accounting for the difference of reactivity.
3. Conclusion
The use of AuCl3 associated with a chiral ligand in the presence
of silver salts was found to be efficient for the preparation of enan-
tiomerically enriched functionalized alcohols and ethers via hydro-
xy- and alkoxycyclization reactions. The reaction conditions were
optimized, the best chiral inductor being the (R)-4-MeO-3,5-(t-
Bu)2-MeOBIPHEP. The carbon-, oxygen- and nitrogen-tethered
enynes reacted smoothly and their cyclization led to various carbo-
cycles and heterocycles in good to excellent yield. The enantiose-
lectivity of the process still needs further optimization as
moderate to good enantiomeric excesses are obtained.
Fig. 1. 13P NMR spectrum for AuCl3/PPh3 (1/1) mixture.
with 2 equiv. of tetrahydrothiophene (tht) in an alcoholic solution
[22].
In a second set of experiments, we studied the nature of the
complex formed from the combination of AuCl3 and MeOBIPHEP.
Upon mixing a 2:1 ratio of AuCl3 and (R)-MeOBIPHEP in CD3CN,
we observed the formation of two products at +23 ppm and
+43 ppm after stirring for 30 min (Scheme 5, Fig. 2). The first signal
could been assigned to MeOBIPHEP(AuCl)2 complex by comparison
with a sample prepared from MeOBIPHEP and (tht)AuCl according
to the literature procedure [25]. On the basis of its chemical shift,
the second signal was assigned to the hydrochloride adduct of the
MeOBIPHEP oxide. Hence, we are assuming that the behavior of the
C2-symmetric chiral bidentate ligand parallels the one observed
with PPh3 and leads to the formation of well-defined Au(I) com-
plexes with a theoretical yield of 50%.
Half of the introduced phosphane playing the role of a sacrificial
reductant, it is remarkable to observe that a variation of the P/Au
ratio from 1 to 2 did not result in a change of the enantioselectivity
(Table 1, entry 9). Under the reaction conditions, we are assuming
that the excess AuCl3 may be reduced by a well-known photo-
chemical process to give inactive Au(0) [26,27], thus hampering
the possibility to observe a background racemic reaction [28]. Fi-
4. Experimental section
AuCl3, Ag salts and PPh3 were commercially available from Cor-
tecnet and Acros and used without further purification. All cata-
lytic manipulations involving air-sensitive reagents were carried
out under argon and Schlenk techniques for catalytic tests. Water,
dioxane, methanol, ethanol and allylic alcohol were degassed by
sparging with argon and/or exposure to vacuum. Column chroma-
tography was performed with 0.040–0.063 mm Art. 11567 silica
gel (E. Merck) or Florisil gel 100–200 mesh (Avocado). Optical-rota-
tion measurements were conducted on a Perkin–Elmer 241 polar-
imeter at 589 nm. High Pressure Liquid Chromatography analyses
(HPLC) were performed on Waters instruments (Waters 486 detec-
tor, 717 autosampler equipped with Daicel Chiralcel OD-H, OJ and
Chiralpak AS-H).
AuCl
O
MeO
MeO
PPh
PPh
MeO
MeO
PPh
PPh
O
MeO
MeO
PPh
PPh
2
2
2
2
2
2
+
.2 HCl
+
1/2
AuCl
1/2
3
AuCl
31
31
(
P) = + 23.1 ppm
δ( P) = + 43.3 ppm
δ
Scheme 5. Proposed catalytic gold species for a AuCl3/(R)-MeOBIPHEP mixture.

544
C.-M. Chao et al. / Journal of Organometallic Chemistry 694 (2009) 538–545
Enynes 1a–b, 4a–b, 7a and 9a were prepared according to pub-
4.1.6. Dimethyl-4-(1-methoxy-methylethyl)-3-methylene-
cyclopentane-1,1-dicarboxylate (3b)
lished procedures [7]. The spectral characterizations of alcohols 2a,
3a, 8a and 10a and ethers 2b, 5b and 6b are identical to those pub-
lished in the literature [7].
Starting from 50 mg of enyne 1b and following the typical pro-
cedure using 6.1 mg (10 mol%) of AuCl3, 11.6 mg of (R)-4-MeO-3,5-
(t-Bu)2-MeOBIPHEP and 20.7 mg of AgSbF6 in 0.36 ml of methanol
at room temperature in 19 h, compound 3b was obtained as a col-
4.1. Typical procedure for gold-catalyzed hydroxy- and
alkoxycyclisation reactions
orless oil (55 mg, 99%). ½a D22
= ꢀ2.0 (c = 0.65, CHCl3). HPLC (Chiracel
ꢂ
OJ, hexane/propan-2-ol (99/1), 1 ml/min, k = 215 nm): 803 and 904,
ee = 30%.
A mixture of AuCl3 (10 mol%, M = 303.32), (R)-4-MeO-3,5-(t-
Bu)2-MeOBIPHEP (5 mol%, M = 1151.6) and AgSbF6 (30 mol%,
M = 343.61), was degassed and stirred 30 min at room temperature
in alcohol or dioxane. The enyne was then added to the mixture
and water if necessary. The mixture was filtered through a short
pad of florisil or silica gel (cyclohexane/EtOAc, 50/50) and the sol-
vents were evaporated under reduced pressure. The crude product
was purified if necessary by silica gel flash chromatography (cyclo-
hexane/EtOAc, 90/10).
4.1.7. 1,1-Bis(phenylsulfonyl)-4-(1-hydroxy-methylethyl)-3-
methylene-cyclopentane (6a)
Starting from 70 mg of enyne 4b and following the typical pro-
cedure using 5.2 mg (10 mol%) of AuCl3, 9.8 mg of (R)-4-MeO-3,5-
(t-Bu)2-MeOBIPHEP and 17.5 mg of AgSbF6 in 0.30 ml of 14% aque-
ous dioxane at room temperature in 24 h, compound 6a was ob-
tained as a colorless oil (70.9 mg, 99%). ½a D22
= ꢀ30.8 (c = 0.81,
ꢂ
CHCl3). HPLC (Chiralpak AS-H, hexane/propan-2-ol (90/10), 1 ml/
min, k = 215 nm): 5107 and 6103, ee = 72%.
4.1.1. Dimethyl-4-(1-hydroxy-phenylmethyl)-3-methylene-
cyclopentane-1,1-dicarboxylate (2a)
Starting from 70 mg of enyne 1a and following the typical pro-
cedure using 1.9 mg (2.5 mol%) of AuCl3, 7.0 mg of (R)-4-MeO-3,5-
(t-Bu)2-MeOBIPHEP and 6.3 mg of AgSbF6 in 0.42 ml of 14% aque-
ous dioxane at room temperature in one day, compound 2a was
4.1.8. 1,1-Bis(phenylsulfonyl)-4-(1-ethoxy-methylethyl)-3-methylene-
cyclopentane (6c)
Starting from 60 mg of enyne 4b and following the typical pro-
cedure using 4.7 mg (10 mol%) of AuCl3, 8.8 mg of (R)-4-MeO-3,5-
(t-Bu)2-MeOBIPHEP and 15.8 mg of AgSbF6 in 0.26 ml of ethanol
at room temperature in 24 h, compound 6c was obtained as a yel-
obtained as a pale yellow oil (51 mg, 99%). ½a D22
= ꢀ54.0 (c = 1.14,
ꢂ
CHCl3). HPLC (Chiralcel OD-H, hexane/propan-2-ol (90/10), 1 ml/
min, k = 215 nm): 1408 and 1806, ee = 72%.
low oil (66 mg, 99%). ½a D22
= ꢀ25.5 (c = 0.51, CHCl3). HPLC (Chir-
ꢂ
alpak AS-H, hexane/propan-2-ol (90/10), 1 ml/min, k = 215 nm):
1708 and 1907, ee = 78%.
4.1.2. Dimethyl-4-(1-methoxy-phenylmethyl)-3-methylene-
cyclopentane-1,1-dicarboxylate (2b)
Starting from 50 mg of enyne 1a and following the typical pro-
cedure using 5.3 mg (10 mol%) of AuCl3, 10 mg of (R)-4-MeO-3,5-
(t-Bu)2-MeOBIPHEP and 17.9 mg of AgSbF6 in 0.30 ml of methanol
at room temperature in 2 days, compound 2b was obtained as a
4.1.9. 4-[1-Hydroxy-(3,4-methylenedioxy)phenylmethyl]-3-
methylene-tetrahydrofuran (8a)
Starting from 50 mg of enyne 7a and following the typical pro-
cedure using 5.8 mg (10 mol%) of AuCl3, 10.9 mg of (R)-4-MeO-3,5-
(t-Bu)2-MeOBIPHEP and 19.6 mg of AgSbF6 in 0.34 ml of 14% aque-
ous dioxane at room temperature in 3 days, compound 8a was ob-
pale yellow oil (57 mg, 99%). ½a D22
= ꢀ17.2 (c = 0.78, CHCl3). HPLC
ꢂ
(Chiracel OJ, hexane/propan-2-ol (99/1), 1 ml/min, k = 215 nm):
3607 and 3900, ee = 30%.
tained as a brown oil (35 mg, 65%). ½a D22
= ꢀ13.6 (c = 0.66, CHCl3).
ꢂ
HPLC (Chiralcel OD-H, hexane/propan-2-ol (98/2), 1 ml/min,
4.1.3. Dimethyl-4-(1-ethoxy-phenylmethyl)-3-methylene-
cyclopentane-1,1-dicarboxylate (2c)
k = 215 nm): 3907 and 4701, ee = 37%.
Starting from 50 mg of enyne 1a and following the typical pro-
cedure using 5.3 mg (10 mol%) of AuCl3, 10 mg of (R)-4-MeO-3,5-
(t-Bu)2-MeOBIPHEP and 17.9 mg of AgSbF6 in 0.30 ml of ethanol
at room temperature in 18 h, compound 2c was obtained as a pale
4.1.10. 4-[1-Methoxy-(3,4-methylenedioxy)phenylmethyl]-3-
methylene-tetrahydrofuran (8b)
Starting from 70 mg of enyne 7a and following the typical pro-
cedure using 9.7 mg (10 mol%) of AuCl3, 18.4 mg of (R)-4-MeO-3,5-
(t-Bu)2-MeOBIPHEP and 33 mg of AgSbF6 in 0.57 ml of methanol at
room temperature in 26 h, compound 8b was obtained as a color-
yellow oil (49 mg, 88%). ½a D22
= ꢀ42.8 (c = 0.60, CHCl3). HPLC (Chira-
ꢂ
cel OJ, hexane/propan-2-ol (99/1), 0.5 ml/min, k = 215 nm): 1700
and 1805, ee = 55%.
less oil (45 mg, 56%). ½a D22
= ꢀ10.1 (c = 0.53, CHCl3). HPLC (Chir-
ꢂ
4.1.4. Dimethyl-4-(1-allyloxy-phenylmethyl)-3-methylene-
cyclopentane-1,1-dicarboxylate (2d)
alpak AS-H, hexane/propan-2-ol (95/5), 1 ml/min, k = 215 nm):
902 and 1000, ee = 33%.
Starting from 50 mg of enyne 1a and following the typical pro-
cedure using 5.3 mg (10 mol%) of AuCl3, 10 mg of (R)-4-MeO-3,5-
(t-Bu)2-MeOBIPHEP and 17.9 mg of AgSbF6 in 0.30 ml of allylic
alcohol at room temperature in 18 h, compound 2d was obtained
4.1.11. 3-[(1-Hydroxy)phenylmethyl]-4-methylene-N-tosyl-
pyrrolidine 10a
Starting from 70 mg of enyne 9a and following the typical pro-
cedure using 6.3 mg (10 mol%) of AuCl3, 13 mg of (R)-4-MeO-3,5-
(t-Bu)2-MeOBIPHEP and 22.1 mg of AgSbF6 in 0.39 ml of 14% aque-
ous dioxane at room temperature in 3 days, compound 10a was ob-
as a pale yellow oil (52 mg, 89%). ½a D22
= ꢀ35.2 (c = 0.63, CHCl3).
ꢂ
HPLC (Chiracel OJ, hexane/propan-2-ol (99/1), 0.8 ml/min,
k = 215 nm): 1202 and 1308, ee = 62%.
tained as a pale yellow oil (75 mg, 99%). ½a D22
= ꢀ22.3 (c = 0.67,
ꢂ
4.1.5. Dimethyl-4-(1-hydroxy-methylethyl)-3-methylene-
cyclopentane-1,1-dicarboxylate (3a)
CHCl3). HPLC (Chiralpak AS-H, hexane/propan-2-ol (90/10), 1 ml/
min, k = 215 nm): 4100 and 4505, ee = 32%.
Starting from 50 mg of enyne 1b and following the typical pro-
cedure using 6.1 mg (10 mol%) of AuCl3, 11.6 mg of (R)-4-MeO-3,5-
(t-Bu)2-MeOBIPHEP and 20.7 mg of AgSbF6 in 0.36 ml of 14% aque-
ous dioxane at room temperature in 4 days, compound 3a was ob-
Acknowledgements
This work was financially supported by the Centre National de
la Recherche Scientifique (CNRS) and the Ministère de l0Education
et de la Recherche. C.-M. Chao and E. Genin thank the Ministère
de l0Education et de la Recherche for grants (2003–2006 and
tained as a colorless oil (36.1 mg, 66%). ½a D22
= ꢀ38 (c = 0.16, CHCl3).
ꢂ
HPLC (Chiralcel OD-H, hexane/propan-2-ol (98/2), 1 ml/min,
k = 215 nm): 1707 and 1906, ee = 24%.

C.-M. Chao et al. / Journal of Organometallic Chemistry 694 (2009) 538–545
(l) L. Zhang, S.A. Kozmin, J. Am. Chem. Soc. 127 (2005) 6962;
545
2006–2009). The authors thank Professor T. Hayashi and Professor
S. Gladiali for (S)-MeO-MOP, (R)-BINAPO and (R)-Ph-BINEPINE li-
gands. The authors are also grateful to Dr. T. Saito (Takasago Inter-
national Corporation) for DTBM-SEGPHOS ligand and highly thank
Dr. M. Scalone (Hoffmann-La Roche) for generous gift of MeOBIP-
HEP ligand and all the MeOBIPHEP analogues.
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