Chiral carbene approach to gold-catalyzed asymmetric cyclization of 1,6-enynes

Article abstract of DOI:10.1016/j.tetlet.2009.11.039

Chiral C₂-symmetric N-heterocyclic carbenes (NHCs) were tested for their stereocontrolling abilities in gold(I)-catalyzed asymmetric cyclization of 1,6-enynes giving the corresponding cyclopentane derivatives with moderate enantioselectivity of

Full text of DOI:10.1016/j.tetlet.2009.11.039

Tetrahedron Letters 51 (2010) 404–406
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Tetrahedron Letters
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Chiral carbene approach to gold-catalyzed asymmetric cyclization of 1,6-enynes
Yasumasa Matsumoto, Khalid B. Selim, Hirotsugu Nakanishi, Ken-ichi Yamada, Yasutomo Yamamoto,
Kiyoshi Tomioka *
Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo, Kyoto 606-8501, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Chiral C -symmetric N-heterocyclic carbenes (NHCs) were tested for their stereocontrolling abilities in
2
Received 13 October 2009
Revised 6 November 2009
Accepted 10 November 2009
Available online 13 November 2009
gold(I)-catalyzed asymmetric cyclization of 1,6-enynes giving the corresponding cyclopentane deriva-
tives with moderate enantioselectivity of up to 59%.
Ó 2009 Elsevier Ltd. All rights reserved.
Gold(I) complexes with phosphanes or N-heterocyclic carbenes
The extremely poor enantioselectivity exhibited by gold com-
plexes 1a and 1b was likely due to the absence of a stereocontrol-
ling group around the Au coordination site. In fact, previously
1
(
NHCs) have emerged as attractive homogeneous catalysts that
2
activate C–C multiple bonds. Several chiral phosphane–Au(I) com-
plexes have been reported to enantioselectively catalyze coupling
1
0a
described X-ray structures
nitrogen of 1a and 1b was fixed to the direction against the Au–
Cl bond, probably due to a interaction between the phenyl
indicated that the aryl group on the
3
4
of aldehydes with isocyanoacetates, cyclization of 1,6-enynes,
5
nucleophilic addition to allenes, and cyclopropanation of alke-
p–p
2
b,6
nes.
To date, however, there are no reports of a chiral NHC–
group on the chiral carbon and the aryl group on the nitrogen. Fur-
thermore, the relatively long bond length between the carbene car-
bon and Au, 1.967 and 1.968 Å as well as 2.286 and 2.268 Å for Au–
Cl of 1a and 1b, respectively, indicated the need for a mechanism to
enable the substituents on the NHC nitrogen to overlay the Au–Cl
bond.
7
Au(I) complex acting as a chiral catalyst. The scarcity of enantio-
selective Au(I)-catalyzed transformations is probably due to the
linear coordination geometry of Au(I),8 in which a reacting multi-
ple bond coordinates at the side of Au(I) opposite to a chiral ligand;
thus, the reaction site is far away from the chiral environment
,9
(
Fig. 1).
We developed a chiral C
Based on the expectation that one of the two aryl groups of a
diarylmethyl group on the NHC nitrogen should be fixed by the
2
-symmetric NHC for asymmetric Cu(I)-
catalyzed conjugate addition of Grignard reagents to 3-substituted
cyclohexenones, where high enantioselectivity and the sense of
asymmetric induction were correlated with the X-ray structures
Chiral
Au
10–12
of NHC–AuCl complexes 1a and 1b (Fig. 2).
The most recent
Ligand
successful Cu(I)-catalyzed asymmetric arylation of allylic bromides
with aryl-Grignard reagents was also indebted to the copper coun-
terparts of 1c and 1d. As part of our continuing studies, we ap-
plied 1a–d to Au(I)-catalyzed asymmetric cyclization of 1,6-
Figure 1. Linear coordination of triple bond–gold–chiral ligand.
1
3
2
enynes. We describe herein a chiral C -symmetric NHC–Au(I)-cat-
alyzed asymmetric cyclization of 1,6-enynes to give the corre-
Ph
Ph
R2
R2
4
,14
sponding cyclopentane products with moderate ee of up to 59%.
4
Ph
Ph
Asymmetric cyclization of enyne 2a in methanol was success-
fully catalyzed by 6 mol % each of N-aryl-NHC–AuCl 1a1 and sil-
ver hexafluoroantimonate at room temperature for 1 h to give
N
N
0a
Au
Cl
N
N
MeO
OMe
1
R1
1
R
R
1
1
5
3
a
in 94% isolated yield (Table 1, entry 1). The enantioselectivity,
R
1a
Au
Cl
however, was poor; only 5% ee by chiral HPLC (DAICEL ChiralPack
Me
Me
Ph
Me
Ph
Me
4a
AD, 2-propanol/hexane = 1/19).
The N-mesitylmethyl version
gave 3a in 93% yield, but also with poor enantioselectivity
of 4% (entry 2).
R2 R2
1
0a
1
b
N
N
1
2
1
1
1
c R = R = H
d R = Me, R = H
e R = R = Me
Me
Me
1
2
Au
Cl
1
2
1b
*
Corresponding author.
E-mail address: tomioka@pharm.kyoto-u.ac.jp (K. Tomioka).
Figure 2. Chiral NHC–AuCl catalyst precursors 1.
0
040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.11.039

Y. Matsumoto et al. / Tetrahedron Letters 51 (2010) 404–406
405
Table 1
a
Chiral NHC–Au(I) 1-catalyzed cyclization of enyne 2a
Ph
Ph
N Au N
R
N
N R
AgSbF6
MeO C
MeO C
2
2
1
AuCl
MeO C
MeO C
2
2
MeOH
rt, time
OMe
2a
3a
MeO C CO Me
MeO C CO Me
2
2
2
2
MeO C
2
Entry
NHC–AuCl 1
Time (h)
Yield (%)
ee (%)
5b
NHC
Au
MeO C
H
1
2
3
4
5
1a
1b
1c
1d
1e
1
2.5
1
1
1
94
93
95
95
95
2
b
4
MeO
8
32
56
+
2
a-Au -NHC(1e)
H
(S)-3a
Observed
a
Figure 3. Perspective view of 1e and stereochemical model for cyclization.
The reaction was conducted with 6 mol % each of
1
and silver
hexafluoroantimonate.
b
The antipode was obtained.
a
p–p interaction with the phenyl group on the chiral carbon.
Looking through the structure of 1e from the chlorine to the Au,
the appearance of the aryl rings on the right-upside and left-down-
side shows the presence of a steric barrier there. The coordination
of the C–C triple bond of 2a to the Au(I) triggers the cyclization by
placing residues in the vacant space as shown to give (S)-3a18 with
the observed absolute configuration.
p–p interaction and hence a free aryl group overlays the Au–Cl
1
3
bond, 1c and 1d bearing a diarylmethyl group on nitrogen were
tested. Although the improvement was very slight (8% ee) with 1c
bearing a diphenylmethyl substituent (entry 3), this substituent
became the basis for further improvement. Attaching one methyl
group on the phenyl ring of 1c would bring a methyl group to
the direction of Au–Cl bond realizing more steric control. In fact,
2
In summary, we developed a chiral C -symmetric NHC–Au(I)
catalyst based on the use of an N-bis(2,5-dimethylphenyl)methyl
substituent endowing a chiral environment around Au(I). The
validity of the concept was evidenced by the moderate enantiose-
lectivity and predictable absolute configuration in the first chiral
NHC–Au(I)-catalyzed asymmetric cyclization of 1,6-enynes. The
results described here provide a basis for the design of much more
efficient chiral NHC–Au(I) catalysts.
1
d with the ortho-methyl group on the phenyl group significantly
improved the enantioselectivity to 32% ee (entry 4). Further intro-
duction of a second methyl group on the 5-position of the phenyl
group was then examined as shown in 1e with expectation of
much more efficient steric bulk.
The new NHC–AuCl complex 1e bearing bis(2,5-dimethyl-
phenyl)methyl substituents was synthesized as an air-stable color-
2
D
5
Acknowledgments
less amorphous of mp 135–138 °C and ½
a
ꢀ
ꢁ236 (c 0.96, CHCl
3
)
starting from (1S,2S)-1,2-diphenylethane-1,2-diamine via bis(2,5-
dimethylphenyl)methylation with the corresponding bromide in
the presence of sodium carbonate in N,N-dimethylpropylene urea
at 120 °C, imidazolium salt formation with orthoformate and
ammonium tetrafluoroborate, and finally, treatment with so-
This research was partially supported by a Grant-in-Aid for Sci-
entific Research in Priority Areas ‘Advanced Molecular Transforma-
tions of Carbon Resources’, a Grant-in-Aid for Scientific Research
1
6
(
A), and the Targeted Proteins Research Program of the Ministry
17
of Education, Culture, Sports, Science, and Technology, Japan.
1
0a
dium t-butoxide and a gold chloride–SMe
2
complex in THF.
To
K.B.S. thanks the Egyptian Government for
fellowship.
a predoctoral
our delight 1e gave the best enantioselectivity of 56% among
examined (entry 5).
The obtained NHC–AuCl 1e could generally be applied to a cat-
alytic asymmetric enyne cyclization of enynes 2b and 2c in meth-
anol at room temperature for 11 h and 1 h to give the
corresponding cyclopentanes 3b with 59% ee and 3c with 52% ee,
respectively, in high chemical yields (Scheme 1).
The sense of the asymmetric induction by 1e–AgSbF catalyst is
6
predictable based on a model structure (Fig. 3). One aryl group of
the bis(2,5-dimethylphenyl)methyl substituent would be fixed by
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