Bulky thioureas as new ligands for gold(I)-catalyzed cyclization of acetylenic 1,3-dicarbonyl compounds

Article abstract of DOI:10.1055/s-2007-983804

We illustrate the first use of bulky N,N′-disubstituted cyclic thioureas as ligands for gold(I) catalysis. X-ray crystal structures of the thiourea-gold(I) complexes presented important information about the nature of the complexation. These complexes wer

Full text of DOI:10.1055/s-2007-983804

SPECIAL TOPIC
2539
Bulky Thioureas as New Ligands for Gold(I)-Catalyzed Cyclization of
Acetylenic 1,3-Dicarbonyl Compounds
B
J
ulkyThi
i
oureas
e
as
N
ewLig
-
andsfor
H
Gold(I)-Catalyze
d
u
Cyclizatio ni Pan, Min Yang, Qiang Gao, Nian-Yong Zhu, Dan Yang*
Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. of China
E-mail: yangdan@hku.hk
Received 5 May 2007
S
S
S
Abstract: We illustrate the first use of bulky N,N¢-disubstituted cy-
R
R
clic thioureas as ligands for gold(I) catalysis. X-ray crystal struc-
tures of the thiourea–gold(I) complexes presented important
information about the nature of the complexation. These complexes
were found to be active catalysts for the cyclization of 1,3-dicarbo-
nyl compounds with alkynes (Conia-ene reaction). Various acety-
lenic 1,3-dicarbonyl compounds underwent cycloisomerization to
give mono- and bicyclic olefinic cyclopentanes in the presence of
one mol% of a thiourea–gold(I) chloride complex and silver triflate.
N
N
N
N
HN
NH
H
H
1
1
a: R = Me
b: R = Ph
1c
1d
S
S
N
N
N
N
Key words: alkynes, catalysis, cyclizations, 1,3-dicarbonyl com-
pounds, ligands
1
e
1f
Figure 1 Structures of thiourea ligands
The use of phosphine ligands for transition metals in orga-
nometallic chemistry and catalysis is widespread. Howev-
er, the air- and moisture-sensitivity of many phosphine
ligands place significant limits on their synthetic applica-
tions. New types of phosphine-free ligands have become
a popular challenge for chemists. Thioureas have attracted
considerable attention as a new type of possible alterna-
tive to the widely used phosphine ligands in ruthenium-,
in gold(I) catalysis, in particular in the cycloisomerization
of 1,3-dicarbonyl compounds with alkynes.
We synthesized cyclic thioureas 1e–h (Figure 1) accord-
3
ing to our previous reports, as well as thiourea–gold(I)
complexes 2d and 2g (Scheme 1). We chose the Conia-
ene reaction to examine the catalytic efficiency of various
thiourea ligand–gold(I) complexes (Table 1). Only 1
mol% of thiourea–gold(I) chloride species and silver tri-
flate was employed to catalyze the reaction at room tem-
perature from alkynic b-keto ester 3a to the desired
cyclopentane derivative 4a. Based on the results shown in
Table 1, the following observations were made: (a) The
preformed gold(I)–thiourea complexes (Table 1, entries 1
and 2) exhibited higher activity than those generated in
situ (entries 3–9), even though the latter is more conve-
nient to use in practice. (b) Gold(I) catalysts complexed
palladium-, and cobalt-catalyzed reactions.1–3 Therefore,
transition-metal-catalyzed reactions using thiourea
ligands are worthy of further investigation.
Gold was considered to be a metal with low catalytic ac-
tivity until, in 1972, Hüttel et al. found that gold(III) chlo-
ride or gold(I) cyanide catalyzed the ring-opening
reaction of bicyclo[1.1.0]butane, a symmetric strained
4
compound. It is now recognized that gold has unique
5
properties as a catalyst for many reactions. Gold(I) cata-
lysts have been found to activate alkynes for nucleophilic
attack and have been widely investigated since the first re-
tBu
6
port in 1985 by Hutchings et al. Recently, Toste and co-
tBu
7
workers applied phosphine–gold(I) complexes in the car-
tBu
tBu
S
bocyclization of b-keto esters with alkynes (also called
the Conia-ene reaction) under mild and neutral conditions.
In the presence of a low catalyst loading (1 mol%) of cat-
S
N
N
N
N
ionic gold complexes generated from [AuCl(PPh )] and
3
tBu
tBu
silver triflate, a series of alkynic b-keto esters gave the cy-
cloisomerization products in high yield. However, the
chemistry of gold(I) catalysts has been mainly focused on
the use of phosphine ligands. Here we report that bulky
N,N¢-disubstituted cyclic thiourea ligands can be applied
tBu
1
g
tBu
1h
TU
+
KAuCl4
Au(TU)Cl
1
1
d
g
2d
2g
SYNTHESIS 2007, No. 16, pp 2539–2544
x
x.
x
x
.
2
0
0
7
Scheme 1 Synthesis of thiourea–gold(I) complexes. Reagents and
conditions: thiourea (TU) (1 equiv), S(CH CH CO H) , CH Cl –
Advanced online publication: 24.07.2007
DOI: 10.1055/s-2007-983804; Art ID: C03207SS
Georg Thieme Verlag Stuttgart · New York
2
2
2
2
2
2
H O, 0 °C to r.t., 2 h.
2
©

2
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J.-H. Pan et al.
SPECIAL TOPIC
Table 1 Screening of Thiourea Ligands for the Gold(I)-Catalyzed
a
Conia-Ene Reaction
O
O
O
O
OMe
OMe
3a
4a
b
Entry
1c
Thiourea
1d
Time
16 h
2.5 h
3 d
Yield (%)
88
96
57
63
70
90
94
93
90
2c
1g
3d
1a
4d
1b
3 d
5d
1c
1 d
6d
1e
8 h
7d
1f
6 h
8d
Figure 2
1g
4.5 h
12 h
9d
1h
Table 2 Selected Data from the X-ray Crystal Structures of 1g and
2g
a
Reaction conditions: 3a (0.3 mmol), Au catalyst (1 mol%), AgOTf
(
1 mol%), CH Cl (1 mL), air, r.t.
Isolated yield.
Au catalyst: Au(TU)Cl (1 mol%).
Au catalyst: AuCl (1 mol%), TU (1 mol%).
2
2
b
1g
2g
[AuCl(PPh )]a
3
c
d
Bond lengths (Å) Au–S(or P)
Au–Cl
2.2541
2.2718
1.69
2.235
2.279
with tetrasubstituted thioureas 1c and 1e–h (Table 1, en-
tries 2 and 5–9) gave higher yields of the cyclization prod-
uct in shorter reaction times than with complexes with
disubstituted thioureas 1a, 1b, and 1d (entries 1, 3 and 4).
S(1)–C(1)
1.657
1.37
N(1)–C(1)
1.346
(
c) High yields were obtained when cyclic thioureas 1e–h
Bond angles (°) Cl–Au–S(or P)
Au(1)–S(1)–C(1)
171.07
111.70
179.63
were employed. The most bulky cyclic thiourea 1g pro-
vided the highest yield and rate of the cyclization reaction
(
Table 1, entries 2 and 8).
a
Data from ref. 8.
X-ray crystal structures of complex 2g and ligand 1g gave
us important information on the nature of N,N¢-diaryl cy- of a wide range of a-alkynic b-keto ester substrates
clic thiourea–gold(I) complexes (Figure 2 and Table 2). (Table 3). With increasing steric size of either the ester
Upon coordination to the gold(I) ion, the S(1)–C(1) bond (Table 3, entry 2) or the ketone moiety (entries 3 and 4),
became longer, whereas the N(1)–C(1) bond was short- slightly longer reaction times are needed. For substrates
ened; this indicates that the interaction of the sulfur atom containing both olefinic and alkynic groups, only the
with gold(I) mainly involves the lone-pair electrons in the alkyne group participates in the cyclization (Table 3, en-
2
sp orbital of the sulfur atom. Distinct from that of tries 5 and 6). The cyclization is applicable not only to b-
8
[
AuCl(PPh )], the X-ray crystal structure of complex 2g keto esters, but also 1,3-diketones and N-monosubstituted
3
revealed that the gold ion lay in the plane of the thiourea b-keto amides (Table 3, entries 7 and 8).
functional group, yet above one of the two phenyl rings
The cyclization catalyzed by the bulky thiourea–gold(I)
bearing two tert-butyl groups. Interestingly, the S–Au–Cl
bond angle is 171° instead of 180°, as expected, with the
Au–Cl bond slightly bent away from the phenyl ring, and
with a distance between Au(1) and the nearest carbon
C(18) of 3.1019 Å, a little longer than that of the calculat-
complex 2g was further applied to the synthesis of bicy-
clic compounds. Conia-ene reactions of cyclopentanone-
and cyclohexanone-bearing substrates afforded the corre-
sponding cis-fused 6,5- and 5,5-bicylic products in high
yields (Table 3, entries 9 and 10). Notably, for starting
materials 3k and 3l with a lactone and a lactam ring, re-
spectively, heterobicyclic products were prepared in ex-
cellent yield (Table 3, entries 11 and 12). Even a-3¢-
alkynyl b-keto ester 3m underwent 5-endo-dig cyclization
+
ed gold–phenyl coordination bond [Au(C H ) , 2.19 Å;
6
6
+
9
Au(C H ) , 2.30 Å; Au(C H ), 2.77 Å]. It is possible that
6
6 2
6
6
the weak interaction between gold(I) and the phenyl ring
may contribute to the high activity of complex 2g.
We then examined the application of bulky thiourea– and produced the corresponding cyclopentene product 4m
gold(I) complex 2g in catalyzing the cycloisomerization in 93% yield (Table 3, entry 13).
Synthesis 2007, No. 16, 2539–2544 © Thieme Stuttgart · New York

SPECIAL TOPIC
Bulky Thioureas as New Ligands for Gold(I)-Catalyzed Cyclization
2541
Table 3 Conia-Ene Reactions Catalyzed by Gold(I)–Thiourea Complex 2g with Silver Triflatea
b
Entry
1
Starting material
Time (h)
2.5
Product
Yield (%)
O
O
O
O
O
O
OMe
3a
3b
3c
3d
3e
4a
4b
4c
4d
4e
96
91
88
85
94
OMe
O
O
t
2
3
4
5
O Bu
3.5
4
t
O Bu
O
O
O
O
iPr
OMe
i
Pr
OMe
O
O
O
O
Ph
OEt
6
Ph
OEt
O
O
O
O
O
3.5
O
O
O
O
O
6
OMe
3f
4
OMe
4f
89
O
O
O
O
7
8
Ph
3g
3h
3
4g
4h
90
93
Ph
O
O
O
O
O
Ph
Ph
H
N
4.5
N
H
COOEt
O
O
9
OEt
3i
3.5
4i
90
H
O
COOMe
O
O
1
1
0
1
OMe
3j
3
4
4j
91
87
H
O
COMe
O
O
3k
4k
O
O
H
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J.-H. Pan et al.
SPECIAL TOPIC
Table 3 Conia-Ene Reactions Catalyzed by Gold(I)–Thiourea Complex 2g with Silver Triflatea (continued)
b
Entry
Starting material
Time (h)
6
Product
Yield (%)
O
O
COMe
O
1
1
2
3
3l
4l
83
93
tBu
N
tBu
N
H
O
O
O
O
3m
2
t
4m
t
O Bu
O Bu
a
Reaction conditions: 3 (0.3 mmol), 2g (1 mol%), AgOTf (1 mol%), CH Cl (1 mL), air, r.t.
Isolated yield.
2
2
b
We next chose to study the carbocyclization of e-acety- spectively (Figure 3). The b¢-substituent is equatorial in
lenic b¢-substituted b-keto esters to examine the stereo- transition state A, whereas it is axial in transition state B.
10
control over two contiguous stereogenic centers. The b- The strong allylic 1,3-strain encountered in transition state
keto ester moiety, through its enol tautomer, should be the B disfavors the formation of products 5, especially those
reactive intermediate in the cyclization reaction and the with large b¢-substituents such as the tert-butyl group.
presence of b¢-substituents could control the transforma-
tion of the keto–enol prochiral group into a new stereo-
genic center. Under the standard conditions of the Conia-
ene cyclization, 3n–q were converted into cycloadducts
AuL
O
O
MeO
AuL
OH
MeO
R
OH
A
B
H
4
n–q and 5n–q with a high level of diastereoselectivity
Me
H H
(
Table 4). Products 4n–q were favored with increasing
H
O
R
size of the b¢-substituents. b¢-Alkyl-substituted com-
pounds gave the cyclization products in higher diastereo-
meric ratios (Table 4, entries 1–3), whereas the compound
with a b¢-phenyl group gave a lower diastereomeric ratio
1,3-strain
O
O
O
(
entry 4). tert-Butyl-substituted substrate 3n gave the
OMe
OMe
R
R
highest diastereoselectivity (Table 4, entry 1).
If it is assumed that the cycloisomerization catalyzed by
the thiourea–gold(I) complex follows a mechanism simi-
4
5
lar to that of [Au(OTf)(PPh )], the diastereoselectivities
3
Figure 3
observed in our study could be explained reasonably by
conformational control. There are two transition states A
and B, leading to the formation of products 4 and 5, re-
In conclusion, we have demonstrated the first use of bulky
N,N¢-disubstituted cyclic thioureas as ligands for gold(I)
catalysis. Some important information about the complex-
ation has been obtained from the X-ray crystal structure of
2g. The combination of 2g with silver triflate has been
found to be an excellent catalyst for the Conia-ene cy-
clization of 1,3-dicarbonyl compounds with alkynes. The
reactions can be readily conducted in high yield under
mild and neutral conditions with a low catalytic loading in
an ‘open flask’ system, and holds high promise in natural
product synthesis.
Table 4 Diastereoselectivity of the Cycloisomerization of Com-
pounds 3n–qa
O
O
O
O
O
O
OMe
OMe
OMe
+
R
R
R
3n–q
4n–q
5n–q
Entry
Starting material
Yield (%)
drb
1
2
3
3n (R = t-Bu)
3o (R = n-Bu)
3p (R = Me)
3q (R = Ph)
96
97
96
88
24.4:1
16.2:1
16.5:1
5.0:1
All reagents and solvents for reactions were used as received. Flash
column chromatography was performed using the indicated sol-
vents on E. Merck silica gel 60 (230–400 mesh ASTM). NMR spec-
tra were recorded in CDCl with TMS as an internal standard at
3
ambient temperature on a Bruker Avance DPX 300 Fourier Trans-
4
1
form Spectrometer operating at 300 MHz for H and 75.47 MHz for
1
3
a
Reaction conditions: 3 (0.3 mmol), 2g (1 mol%), AgOTf (1 mol%),
C, or a Bruker Avance DPX 400 Fourier Transform Spectrometer
1
13
CH Cl (1 mL), air, r.t.
operating at 400 MHz for H and 100 MHz for C. Mass spectra
were recorded on a Finnigan MAT 95 mass spectrometer for both
low-resolution and high-resolution mass spectra. IR absorption
2
2
b
1
The dr was determined by use of the H NMR integration of the
methyl ester groups.
Synthesis 2007, No. 16, 2539–2544 © Thieme Stuttgart · New York

SPECIAL TOPIC
Bulky Thioureas as New Ligands for Gold(I)-Catalyzed Cyclization
2543
spectra were recorded as a solution in CH Cl on a Bio-Rad FTS
J = 2.0 Hz, 1 H), 5.21 (t, J = 2.0 Hz, 1 H), 4.18–4.07 (m, 2 H), 2.85
2
2
1
65 Fourier Transform Spectrophotometer. X-ray crystallographic
(dt, J = 13.6, 7.0 Hz, 1 H), 2.51 (tt, J = 7.4, 2.0 Hz, 2 H), 2.18 (dt,
J = 13.6, 7.0 Hz, 1 H), 1.92–1.81 (m, 1 H), 1.74–1.63 (m, 1 H), 1.05
(t, J = 7.1 Hz, 3 H).
data collection was performed on an Enraf-Nonius CAD4 single
crystal diffractometer or a Rigaku AFC 7R rotating anode X-ray
single crystal diffractometer.
Compound 4e
Yield: 94%.
Thiourea–Gold(I) Chloride Complex 2g; Typical Procedure
S(CH CH CO H) (53 mg, 0.3 mmol) was added slowly to a soln of
2
2
2
2
1
H NMR (300 MHz, CDCl ): d = 5.97–5.84 (m, 1 H), 5.36–5.22 (m,
3
KAuCl (37.8 mg, 0.1 mmol) in H O (2 mL) at 0 °C. After the mix-
4
2
2
H), 5.29 (t, J = 2.0 Hz, 1 H), 5.24 (t, J = 2.0 Hz, 1 H), 4.65 (t,
J = 1.3 Hz, 1 H), 4.63 (t, J = 1.3 Hz, 1 H), 2.49–2.37 (m, 3 H), 2.22
s, 3 H), 2.24–2.15 (m, 1 H), 1.80–1.65 (m, 2 H).
ture had stirred for 10 min, a soln of thiourea ligand 1g (48 mg, 0.1
mmol) in CH Cl (3 mL) was added dropwise over 20 min while
2
2
(
stirring of the mixture continued. After stirring had continued at r.t.
for 1.5 h, the organic layer was separated and washed with brine (2
mL). The organic layer was dried (Na SO ) and concentrated. The
Compound 4f
Yield: 89%.
2
4
residue was purified by recrystallization (CH Cl –MeOH); this af-
2
2
1
H NMR (300 MHz, CDCl ): d = 5.82–5.73 (m, 1 H), 5.29 (t, J = 2.0
forded complex 2g.
3
Hz, 1 H), 5.22 (t, J = 2.0 Hz, 1 H), 5.06–4.95 (m, 2 H), 3.74 (s, 3 H),
Yield: 66 mg (93%).
2
.74–2.51 (m, 2 H), 2.48–2.29 (m, 5 H), 2.31–2.15 (m, 1 H), 1.81–
–
1
IR (CH Cl ): 1422, 1254 cm .
1.60 (m, 2 H).
2
2
1
H NMR (300 MHz, CDCl ): d = 7.55–7.46 (m, 4 H), 6.86 (s, 2 H),
3
Compound 4g
Yield: 90%.
4
.26–4.23 (m, 2 H), 4.07–4.04 (m, 2 H), 1.53 (s, 18 H), 1.33 (s, 18 H).
1
3
C NMR (75.5 MHz, CDCl ): d = 182.0, 151.5, 144.5, 136.8,
3
1
H NMR (400 MHz, CDCl ): d = 7.78 (app d, J = 7.9 Hz, 2 H), 7.52
3
1
29.6, 127.2, 126.6, 54.3, 35.7, 34.3, 32.1, 31.0.
(
app t, J = 8.0 Hz, 1 H), 7.41 (app t, J = 6.0 Hz, 2 H), 5.41 (t, J = 2.0
Hz, 1 H), 5.12 (t, J = 2.0 Hz, 1 H), 2.77–2.70 (m, 1 H), 2.59–2.45
m, 2 H), 2.29–2.18 (m, 1 H), 2.24 (s, 3 H), 1.86–1.72 (m, 2 H).
+
ESI-MS: m/z (%) = 1153 (100) [L Au ].
2
(
2
d
Yield: 93%.
Compound 4h
Yield: 93%.
1
H NMR (300 MHz, CD OD ): d = 4.86 (s, 4 H), 3.32–3.30 (m, 1 H).
3
1
1
3
H NMR (400 MHz, CDCl ): d = 8.50 (br s, 1 H), 7.52 (app d,
C NMR (75.5 MHz, CD OD): d = 181.7, 44.5.
3
3
J = 7.9 Hz, 2 H), 7.32 (app t, J = 8.0 Hz, 1 H), 7.12 (app t, J = 6.0
Hz, 2 H), 5.42 (t, J = 2.0 Hz, 1 H), 5.32 (t, J = 2.0 Hz, 1 H), 2.67–
+
10
ESI-MS: m/z (%) = 401 (100) [L Au ].
2
2
.52 (m, 3 H), 2.50–2.37 (m, 1 H), 2.29 (s, 3 H), 1.87–1.75 (m, 2 H).
Compound 4a by a Conia-Ene Reaction Catalyzed by a Thio-
urea–Gold(I) Chloride Complex; Typical Procedure
Compound 4i
Yield: 90%.
To a small screw-cap sample vial equipped with a magnetic stir bar
and charged with a soln of 3a (91 mg, 0.5 mmol) in CH Cl (1 mL)
2
2
1
H NMR (400 MHz, CDCl ): d = 5.22 (t, J = 2.4 Hz, 1 H), 4.98 (t,
was added 2g (1 mol%) followed by AgOTf (1 mol%). The cloudy
white reaction mixture was then stirred at r.t. and monitored period-
ically by TLC. Upon completion, the solvent was removed and the
residue was purified by flash column chromatography (n-hexane–
EtOAc, 9:1); this gave 4a.
3
J = 2.4 Hz, 1 H), 4.28–4.18 (m, 2 H), 3.04 (app quin, J = 7.2 Hz, 1
H), 2.51–2.46 (m, 2 H), 2.43–2.36 (m, 2 H), 1.97–1.84 (m, 3 H),
1
.71–1.64 (m, 1 H), 1.58–1.50 (m, 2 H), 1.26 (t, J = 7.0 Hz, 3 H).
Compound 4j
Yield: 91%.
Yield: 87 mg (96%).
1
H NMR (300 MHz, CDCl ): d = 5.30 (t, J = 2.0 Hz, 1 H), 5.23 (t,
1
3
H NMR (400 MHz, CDCl ): d = 5.36 (t, J = 2.4 Hz, 1 H), 5.21 (t,
3
J = 2.0 Hz, 1 H), 3.75 (s, 3 H), 2.48–2.36 (m, 3 H), 2.22 (s, 3 H),
J = 2.0 Hz, 1 H), 3.71 (s, 3 H), 3.25–3.18 (m, 1 H), 2.52–2.48 (m, 2
H), 2.45–2.40 (m, 2 H), 2.19–2.10 (m, 1 H), 2.06–1.97 (m, 1 H),
2
.24–2.15 (m, 1 H), 1.76–1.64 (m, 2 H).
1
.67–1.56 (m, 2 H).
Compound 4b
Yield: 91%.
Compound 4k
Yield: 87%.
1
H NMR (400 MHz, CDCl ): d = 5.28 (t, J = 2.0 Hz, 1 H), 5.23 (t,
3
J = 2.0 Hz, 1 H), 2.43–2.33 (m, 3 H), 2.21 (s, 3 H), 2.15–2.10 (m, 1
H), 1.73–1.59 (m, 2 H), 1.47 (s, 9 H).
1
H NMR (400 MHz, CDCl ): d = 5.58 (t, J = 2.0 Hz, 1 H), 5.33 (t,
3
J = 1.9 Hz, 1 H), 4.37 (dd, J = 9.3, 7.9 Hz, 1 H), 3.98 (dd, J = 9.3,
4
2
.9 Hz, 1 H), 3.53–3.49 (m, 1 H), 2.54–2.47 (m, 2 H), 2.44 (s, 3 H),
.20–2.11 (m, 1 H), 1.67–1.58 (m, 1 H).
Compound 4c
Yield: 88%.
1
H NMR (400 MHz, CDCl ): d = 5.30 (t, J = 2.0 Hz, 1 H), 5.23 (t,
Compound 4l
Yield: 83%.
3
J = 2.0 Hz, 1 H), 3.74 (s, 3 H), 2.98 (sept, J = 6.7 Hz, 1 H), 2.48–
2
.42 (m, 2 H), 2.40–2.35 (m, 1 H), 2.30–2.23 (m, 1 H), 1.76–1.63
1
H NMR (300 MHz, CDCl ): d = 5.53 (t, J = 2.2 Hz, 1 H), 5.21 (t,
3
(
m, 2 H), 1.10 (d, J = 6.6 Hz, 3 H), 1.07 (d, J = 6.6 Hz, 3 H).
J = 2.2 Hz, 1 H), 3.53 (dd, J = 8.3, 10.6 Hz, 1 H), 3.14–3.05 (m, 2
H), 2.44–2.31 (m, 2 H), 2.37 (s, 3 H), 2.12–2.01 (m, 1 H), 1.50–1.39
Compound 4d
Yield: 85%.
(m, 1 H), 1.37 (s, 9 H).
1
H NMR (300 MHz, CDCl ): d = 7.84 (app d, J = 7.4 Hz, 2 H), 7.52
td, J = 7.4, 1.2 Hz, 1 H), 7.42 (app t, J = 7.4 Hz, 2 H), 5.36 (t,
Compound 4m
Yield: 93%.
3
(
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J.-H. Pan et al.
SPECIAL TOPIC
1
H NMR (400 MHz, CDCl ): d = 5.66 (br s, 1 H), 2.58 (m, 1 H), References
3
2
3
.42–2.24 (m, 2 H), 2.16 (s, 3 H), 2.11 (m, 1 H), 1.81 (q, J = 2.4 Hz,
(
1) (a) Munno, G. D.; Gabriele, B.; Salerno, G. Inorg. Chim.
Acta 1995, 234, 181. (b) Gabriele, B.; Salerno, G.; Costa,
M.; Chiusoli, G. P. J. Organomet. Chem. 1995, 503, 21.
H), 1.47 (s, 9 H).
The complete spectroscopic and analytical data of known com-
pounds 4a–m have been published elsewhere.
7
(c) Touchard, F.; Fache, F.; Lemaire, M. Tetrahedron:
Asymmetry 1997, 8, 3319. (d) Touchard, F.; Gamez, P.;
Fache, F.; Lemaire, M. Tetrahedron Lett. 1997, 38, 2275.
Compounds 4n and 5n
Yield: 96%.
(
e) Touchard, F.; Bernard, M.; Fache, F.; Delbecq, F.;
1
H NMR (400 MHz, CDCl ): d = 5.03 (t, J = 2.3 Hz, 1 H), 4.92 (t,
Guiral, V.; Sautet, P.; Lemaire, M. J. Organomet. Chem.
1998, 567, 133. (f) Touchard, F.; Bernard, M.; Fache, F.;
Lemaire, M. J. Mol. Catal. A: Chem. 1999, 140, 1.
(g) Zhang, T. Y.; Allen, M. J. Tetrahedron Lett. 1999, 40,
3
J = 2.7 Hz, 1 H), 3.67 (s, 3 H), 2.64–2.60 (m, 1 H), 2.50–2.45 (m, 1
H), 2.39 (s, 3 H), 1.52–1.43 (m, 1 H), 1.30–1.25 (m, 2 H), 0.85 (s, 9
H).
5813. (h) Tommasino, M. L.; Casalta, M.; Breuzard, J. A. J.;
Compounds 4o and 5o
Yield: 97%.
Lemaire, M. Tetrahedron: Asymmetry 2000, 11, 4835.
(i) Breuzard, J. A. J.; Tommasino, M. L.; Touchard, F.;
Lemaire, M.; Bonnet, M. C. J. Mol. Catal. A: Chem. 2000,
1
H NMR (400 MHz, CDCl ): d = 5.23 (t, J = 2.2 Hz, 1 H), 5.17 (t,
3
156, 223.
J = 2.8 Hz, 1 H), 3.71 (s, 3 H), 2.73–2.70 (m, 1 H), 2.48–2.46 (m, 1
H), 2.35–2.29 (m, 1 H), 2.25 (s, 3 H), 1.96–1.89 (m, 1 H), 1.52–1.41
(
2) (a) Dai, M.; Wang, C.; Liang, B.; Chen, J.; Yang, Z. Eur. J.
Org. Chem. 2003, 4346. (b) Dai, M.; Liang, B.; Wang, C.;
Chen, J.; Yang, Z. Org. Lett. 2004, 6, 221. (c) Dai, M.;
Liang, B.; Wang, C.; You, J. Z.; Yang, Z. Adv. Synth. Catal.
(
m, 1 H), 1.40–1.10 (m, 6 H), 0.86 (t, J = 6.6 Hz, 3 H).
Compounds 4p and 5p
Yield: 96%.
2004, 346, 1669. (d) Xiong, Z.; Wang, N.; Dai, M.; Yang, Z.
Org. Lett. 2004, 6, 3337. (e) Tang, Y.; Deng, L.; Zhang, Y.;
Dong, G.; Chen, J.; Yang, Z. Org. Lett. 2005, 7, 593.
1
H NMR (400 MHz, CDCl ): d = 5.27 (t, J = 1.6 Hz, 1 H), 5.24 (t,
3
J = 2.2 Hz, 1 H), 3.71 (s, 3 H), 2.87–2.80 (m, 1 H), 2.58–2.50 (m, 1
H), 2.42–2.30 (m, 1 H), 2.22 (s, 3 H), 1.98–1.89 (m, 1 H), 1.49–1.40
(
f) Tang, Y.; Zhang, Y.; Dai, M.; Luo, T.; Deng, L.; Chen, J.;
Yang, Z. Org. Lett. 2005, 7, 885.
(
m, 1 H), 0.92 (d, J = 6.6 Hz, 3 H).
(
3) (a) Yang, D.; Chen, Y.-C.; Zhu, N.-Y. Org. Lett. 2004, 6,
1
577. (b) Yang, M.; Yip, K.-T.; Pan, J.-H.; Chen, Y.-C.;
Compounds 4q and 5q
Yield: 88%.
Zhu, N.-Y.; Yang, D. Synlett 2006, 3057.
(
(
4) Gassman, P. G.; Meyer, G. R.; Williams, F. J. J. Am. Chem.
Soc. 1972, 94, 7741.
5) For reviews of gold-catalyzed reactions, see: (a) Dyker, G.
Angew. Chem. Int. Ed. 2000, 39, 4237. (b) Hashmi, A. S. K.
Gold Bull. 2003, 23, 3. (c) Hashmi, A. S. K. Gold Bull.
Compound 4q
1
H NMR (400 MHz, CDCl ): d = 7.29–7.23 (m, 5 H), 5.40 (dd,
3
J = 2.7, 1.6 Hz, 1 H), 5.36 (dd, J = 2.7, 1.6 Hz, 1 H), 4.30 (dd,
J = 9.3, 7.1 Hz, 1 H), 3.21 (s, 3 H), 2.57–2.40 (m, 2 H), 2.29 (s, 3
H), 2.19–2.11 (m, 2 H).
2004, 24, 51. (d) Hashmi, A. S. K.; Hutchings, G. J. Angew.
Chem. Int. Ed. 2006, 45, 7896. (e) Gorin, D. J.; Toste, F. D.
Nature 2007, 446, 395.
Compound 5q
1
(
6) Hutchings, G. J. J. Catal. 1985, 96, 292.
H NMR (400 MHz, CDCl ): d = 7.21–7.14 (m, 5 H), 5.26 (dd,
3
(7) (a) Kennedy-Smith, J. J.; Staben, S. T.; Toste, F. D. J. Am.
Chem. Soc. 2004, 126, 4526. (b) Staben, S. T.; Kennedy-
Smith, J. J.; Toste, F. D. Angew. Chem. Int. Ed. 2004, 43,
J = 2.7, 1.6 Hz, 1 H), 5.18 (dd, J = 2.7, 1.6 Hz, 1 H), 4.20 (dd,
J = 6.6, 5.5 Hz, 1 H), 3.81 (s, 3 H), 2.76–2.63 (m, 2 H), 2.10–2.02
(
m, 2 H), 1.5 (s, 3 H).
5350. (c) For an enantioselective Conia-ene reaction, see:
Corkey, B. K.; Toste, F. D. J. Am. Chem. Soc. 2005, 127,
17168.
8) Baenziger, N. C.; Bennett, W. E.; Soboroff, D. M. Acta
Crystallogr., Sect. B 1976, 32, 962.
The complete spectroscopic and analytical data of known com-
pounds 4n–q and 5n–q have been published elsewhere.
1
1
(
Acknowledgment
(9) Schröder, D.; Brown, R.; Schwertfeger, P.; Schwarz, H. Int.
J. Mass Spectrom. 2000, 203, 155.
10) Ahmad, S.; Isab, A. A.; Perzanowski, H. P. Can. J. Chem.
This work was supported by the University of Hong Kong and the
Hong Kong Research Grants Council.
(
(
2002, 80, 1279.
11) Cruciani, P.; Stammler, R.; Aubert, C.; Malacria, M. J. Org.
Chem. 1996, 61, 2699.
Synthesis 2007, No. 16, 2539–2544 © Thieme Stuttgart · New York