Au(I)-catalyzed efficient synthesis of α-acyloxy-α′-silyl ketones from α-acyloxy-α-alkynylsilanes

Article abstract of DOI:10.1016/j.tetlet.2007.11.023

The Au(I)-catalyzed novel conversion of α-acyloxy-α-alkynylsilanes to α-acyloxy-α′-silyl ketones is reported. Ph₃PAuOTf in dioxane in the presence of 1 equiv of H₂O efficiently catalyzed both the [3,3] sigmatropic rearrangement and a

Full text of DOI:10.1016/j.tetlet.2007.11.023

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 25–28
Au(I)-catalyzed efficient synthesis of a-acyloxy-a0-silyl
ketones from a-acyloxy-a-alkynylsilanes
Kazuhiko Sakaguchi,* Takuya Okada, Tetsuro Shinada and Yasufumi Ohfune*
Graduate School of Science, Osaka City University, Sugimoto, Osaka 558-8585, Japan
Received 13 October 2007; revised 2 November 2007; accepted 5 November 2007
Available online 7 November 2007
Dedicated to the late Professor Yoshihiko Ito
Abstract—The Au(I)-catalyzed novel conversion of a-acyloxy-a-alkynylsilanes to a-acyloxy-a0-silyl ketones is reported. Ph3PAuOTf
in dioxane in the presence of 1 equiv of H2O efficiently catalyzed both the [3,3] sigmatropic rearrangement and allenic transforma-
tion of the resulting ester to give the a-acyloxy-a0-silyl ketones in a one-pot procedure.
Ó 2007 Elsevier Ltd. All rights reserved.
OCOR1
OCOR1
R2
The a-acyloxy ketone is not only a significant synthetic
building block,1 but also a possible precursor of a-
hydroxy ketone which is present in substantial numbers
of both biologically active natural and synthetic mole-
cules.2 On the other hand, a-silyl ketones can be used
for the regioselective generation of an enolate equiva-
lent.3 Furthermore, oxidative cleavage of a carbon–
silicon bond with an electron-withdrawing silicon
substituent allows the conversion of the silyl group to
a hydroxy group.4 Therefore, the regioselective prepara-
tion of an a-acyloxy ketone with an additional function-
ality would expand its utility in organic synthesis. In this
Letter, we describe a novel method to access the titled
a-acyloxy ketone bearing a synthetically useful a-silyl
ketone by the Au(I)-catalyzed reaction of a-acyloxy-a-
alkynylsilanes.
cascade reaction
products
OCOR1
Alk
Si
cat. Au
X
1
α'
X = Alkyl
R2
α
Au
R2
Si
cat. Au
or oxocarbenium ion
O
3
H2O
Au
X
•
OCOR1
cat. Au
X = Si
OCOR1
and/or
Si
OCOR1
Au
2
R2
R2
R2
Si = TBDMS or Me2PhSi
Scheme 1.
at the allenic center stabilized by the silyl group.8–10
The unprecedented generation of the cation and its trap-
ping with H2O would give rise to an a-acyloxy-a0-silyl
ketone 3 (Scheme 1).
To examine this hypothesis, the readily available a-acet-
oxy-a-alkynylsilane 1a7 was treated with 3 mol % of
[(Ph3PAu)3O]BF4, used for the Claisen rearrangement
of a propargyl vinyl ether11 in CH2Cl2. To our delight,
the reaction produced a mixture of an allene 2a (10%)
and a-acetoxy-a0-silyl ketone 3a (47%). Apparently, 2a
is a product of the Au(I)-catalyzed [3,3] rearrangement.
Au salts are powerful soft Lewis acids and readily acti-
vate alkynes and allenes toward attacks by a variety of
nucleophiles.5 The catalyst plays a dual role for the
[3,3] sigmatropic rearrangement of a propargyl ester
and activation of the resulting allene to give a series of
cascade reaction products via a cationic vinyl-Au species
(putatively, an allyl cation) at the allenic terminus
(Scheme 1).6 We hypothesized that a propargyl ester 1
attached to an a-silyl group7 would undergo the Au-cata-
lyzed rearrangement to give allene 2 whose successive
activation by the Au salt would generate a vinyl cation
OAc
OAc
[(Ph3PAu)3O]BF4
TBDMS
•
OAc
TBDMS
TBDMS
CH2Cl2, rt, 20 h
O
1a
2a
10%
0%*
3a
47%
60%*
*in the presence of 1 equiv H2O
*
Corresponding authors. Tel.: +81 6 6605 2570; fax: +81 6 6605 3153
(Y.O.); e-mail: ohfune@sci.osaka-cu.ac.jp
Scheme 2.
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.11.023

26
K. Sakaguchi et al. / Tetrahedron Letters 49 (2008) 25–28
Table 1. Catalyst optimization using 1aa
Entry
Catalyst
mol %
Temperature (°C)
Time (h)
2ab (%)
3ab (%)
1
2
3
4
5
6
7
8
9
[(Ph3PAu)3O]BF4
Ph3PAuCl/AgBF4
Ph3PAuCl/AgSbF6
Ph3PAuCl/AgOTf
AuCl
AuCl3
AgSbF6
AgBF4
AgOTf
3
3
5
3
5
2
5
5
5
3
5
rt
rt
rt
rt
rt
rt
100
100
100
80
rt
24
2
4
4
1
0.25
22
22
6
3
12
0
0
0
74
41
74
91
0
0
0
0
0
0
45
40
0
66
0
10
11
PtCl2
Hg(OAc)2
35
0
0
0
a All the reactions were carried out using dioxane in the presence of 1 equiv of H2O.
b Isolated yield (%) after column chromatography.
We considered that ketone 3a was produced from the
Au-catalyzed allenic transformation of 2a via the initial
formation of the putative vinyl cation species and subse-
quent trapping with contaminated water in the solvent.
In fact, the addition of 1 equiv of H2O to the reaction
resulted in the exclusive formation of 3a (60%, Scheme
2).12 It was found that dioxane in the presence of 1 equiv
of H2O was an appropriate solvent system for this trans-
formation (74%; CH3CN, 19%; DMF, 29%; THF, 50%).
mediate as proposed by Zhang et al. (Schemes 1 and
3).6a,b,d,i
To gain mechanistic insights into the transformation of
1 to 3, the optically active (R)-1a (>95% ee) was treated
with the optimized reaction conditions. The reaction
gave 3a with complete loss of the starting optical purity.
The use of D2O gave deuterated 3a in which the D
atoms were incorporated into both the a- and a0-posi-
tions (a, 70% D; a0, 58% D). The excess incorporation
of the D atom would be due to the Au-catalyzed epimer-
ization of 2.17 The reaction of the diastereomerically
The catalyst screening indicated that Ph3PAuOTf
(3 mol %), prepared in situ from Ph3PAuCl and AgOTf,
in dioxane–H2O (1 equiv) was found to be superior to
the other Au catalysts (Table 1).13 The reaction was
completed within 4 h at room temperature to give 3a
(91%, entry 4). Au salts, such as AuCl and AuCl3,
catalyzed the [3,3] rearrangement to give 2a, but did
not catalyze any further reactions (entries 5 and 6).
Among other catalysts, AgBF4 and PtCl2 catalyzed the
rearrangement (entries 8 and 10). These results indicated
that more electrophilic Au catalyst plays a dual role for
activation of both the propargyl ester 1a and resulting
allenol ester 2a.
Table 2. Au-Catalyzed formation of a-acyloxy-a0-silyl ketones
OR1
OR1
Ph3PAuOTf (3 mol%)
in dioxane
OR1
α
α'
TBDMS
R2
R2
TBDMS
or
TBDMS
H2O (1 equiv)
O
R2
O
4a,b
1a-k
3a-i
Entry R1
R2
Time Product Yielda
(h)
(%)
1
2
3
4
5
6
7
8
9
Ac (1a)
Piv (1b)
Bz (1c)
p-OMeBz (1d) Me
Boc-Gly (1e) Me
Boc-L-Phe (1f) Me
Ac (1g)
Ac (1h)
Ac (1i)
Ac (1j)
Ac (1k)
Me
Me
Me
4
4
14
5
6
7
4
22
5
10
8
3a
3b
3c
3d
3e
3f
91
89
0b
We next applied the optimized reaction conditions to
other substrates possessing various acyl groups and
alkyne substituents (Table 2). The reaction tolerates
sterically bulky pivaloyl and electron-donating
p-methoxybenzoyl esters to give the corresponding
products 3b,d in good yields, respectively (entries 2
and 4). An alkyl, phenyl, or p-methoxyphenyl alkyne
substituent also gave 3g–i in good to excellent yields
(entries 7–9). It is noteworthy that N-Boc amino acid
esters 1e,f also rearranged into the corresponding a-
acyloxy ketones 3e,f (entries 5, 6, vide infra). On the
other hand, the p-nitrophenyl substituted and unsubsti-
tuted alkynes 1j,k gave a-acyloxy-a-silyl ketones 4a,b
(entries 10 and 11).5j In these cases, the generation of
a b-silylvinyl cation or 5-exo-dig cyclization would take
place over the [3,3] rearrangement (Scheme 3).14 The
regioselectivity upon generation of either the vinyl or
allyl cation species apparently depends on the a-substi-
tuent of the propargyl esters. Treatment of t-butyl
propargyl acetate 5 under the same reaction conditions
gave the a,b-unsaturated ketone 6 (92%).15,16 This result
is in good agreement with the cationic vinyl gold inter-
68
85
74c
91
65d
95
83
79
n-Bu
Ph
p-MeOPh
p-NO2Ph
H
3g
3h
3i
10
11
4a
4b
a Isolated yield after column chromatography.
b Recovery of 1c.
c A mixture of 1:1 diastereomers.
d With 5 mol % catalyst employed and 22% recovery of 1h.
OAc
OAc
Au (I)
H2O
4a R =
p
-NO2Ph
1j,k
TBDMS
Au
TBDMS
R
t
4b R = H
O
R
OAc
OAc
O
3 mol% Ph3PAuOTf
dioxane, H2O (1 equiv)
t
-Bu
-Bu
t
-Bu
n
-Bu
n-Bu
5
n-Bu
rt, 24 h
92%
Au
6
Scheme 3.

K. Sakaguchi et al. / Tetrahedron Letters 49 (2008) 25–28
27
pure (R,S)-1f also afforded a 1:1 mixture of diasteromers
Acknowledgment
3f, which were obtained from 1f (entry 6), whose meth-
anolysis gave an optically pure Boc-L-Phe (Supplemen-
tary data). These results suggested that the allene
epimerization and/or non-stereoselective protonation
occurred at the ester counterparts during the Au-cata-
lyzed allenic transformations (Scheme 1). The removal
of the silyl group from 3f afforded a-acyloxy ketone 7,
a precursor for the asymmetric Strecker synthesis of a-
methylthreonines (Scheme 4).18
This study was supported by a Grant-in-Aid (16201045)
for Scientific Research from the Japan Society for the
Promotion of Science (JSPS).
Supplementary data
Experimental and spectral data of all new compounds.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2007.11.023.
Next, we examined the present reaction using other silyl
groups. An intriguing entry is the use of the dimethyl-
phenylsilyl group, which can be viewed as a masked
hydroxy group.4 However, the Au-catalyzed reaction
of 8 under the optimized conditions resulted in almost
the recovery of 8 even after 15 h. We considered that
the highly electrophilic Au catalyst was inactivated for
the [3,3] rearrangement by interacting with the phenyl
group attached to the silicon. Thus, switching the cata-
lyst and solvent systems to a less electron deficient
[(Ph3PAu)3O]BF4 in CH2Cl2–H2O (1 equiv), which was
very effective for this transformation, gave 9 in 86%
yield (Scheme 5). The silicon–carbon bond was cleaved
after converting 9 to 10 to give alcohol 11 (88%,
dr = 2:1). As an attempt for the regioselective aldol
condensation of 9, treatment with benzaldehyde in the
presence of BF3–OEt2 gave a mixture of the aldol
diastereomers 12 (87%, dr = 7:1).3a
References and notes
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In summary, various a-acyloxy-a0-silyl ketones were
synthesized by the Au(I)-catalyzed reactions of a-acyl-
oxy-a-alkynylsilanes. The reaction proceeded in a mild
and regioselective manner via the putative vinyl cation
stabilized by the silyl group. The rearranged product
possessing an amino acid ester group adds a new and
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Strecker precursor, which leads to various a,a-disubsti-
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O
O
NHBoc
NHBoc
TBAF, AcOH
THF. rt, 1 h
O
O
(
R,S)-1f
Bn
Bn
dr = 1:1
TBDMS
82%
O
O
7
3f
(Strecker precursor)
Scheme 4.
OAc
OAc
OAc
3 mol% [(Ph3PAu)3O]BF4
CH2Cl2, H2O (1 equiv)
1. DIBAL
Si
Si
10
Si
rt, 17 h
86%
2. AcOH, EDCI,
DMAP
9
OAc
O
8
PhCHO
BF3-OEt2
52% (dr = 2:1)
KBr,AcO2H,
Si = Me2PhSi
87%
NaOAc, AcOH
OAc
OAc
dr = 7:1
rt, 16 h
88%
Ph
12
HO
11
OAc
OH
O
Scheme 5.

28
K. Sakaguchi et al. / Tetrahedron Letters 49 (2008) 25–28
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