Gold-catalyzed regioselective hydration of propargyl acetates assisted by a neighboring carbonyl group: Access to α-acyloxy methyl ketones and synthesis of (±)-actinopolymorphol B

Article abstract of DOI:10.1021/jo101995g

A general atom-economical approach for the synthesis of α-acyloxy methyl ketone is demonstrated through regioselective hydration of a wide range of propargyl acetates. Readily available catalyst comprising of 1% Ph ₃PAuCl and 1% AgSbF₆ in dioxane-H₂O efficiently hydrolyzes the terminal alkynes of the propargyl acetate in the absence of acid promoters at ambient temperature within a short time. Effective regioselective hydration is facilitated by the neighboring carbonyl group as demonstrated through ¹⁸O-labeling study. Compatibility of functional moieties and tolerance to various acid-labile protecting groups are observed. The catalytic condition is also suitable to perform hydration of TMS-substituted propargyl acetates, even though it requires prolonged reaction time for completion. Stereointegrity of the propargylic acetate is preserved during the hydration. The robustness of the system is successfully demonstrated through gram scale preparation of the product in nearly quantitative yield. The common α-acyloxy methyl ketone is transformed to 1,2-diol and 1,2-amino alcohol derivatives. Synthesis of actinopolymorphol B is achieved for the first time involving hydration of the propargyl acetate as the key step.

Full text of DOI:10.1021/jo101995g

pubs.acs.org/joc
Gold-Catalyzed Regioselective Hydration of Propargyl Acetates Assisted
by a Neighboring Carbonyl Group: Access to r-Acyloxy Methyl Ketones
and Synthesis of (()-Actinopolymorphol B†
Nayan Ghosh, Sanatan Nayak, and Akhila K. Sahoo*
School of Chemistry, University of Hyderabad, Hyderabad 500046, India
akssc@uohyd.ernet.in
Received October 8, 2010
A general atom-economical approach for the synthesis of R-acyloxy methyl ketone is demonstrated through
regioselective hydration of a wide range of propargyl acetates. Readily available catalyst comprising of 1%
Ph3PAuCl and 1% AgSbF6 in dioxane-H2O efficiently hydrolyzes the terminal alkynes of the propargyl
acetate in the absence of acid promoters at ambient temperature within a short time. Effective regioselective
hydration is facilitated by the neighboring carbonyl group as demonstrated through 18O-labeling study.
Compatibility of functional moieties and tolerance to various acid-labile protecting groups are observed.
The catalytic condition is also suitable to perform hydration of TMS-substituted propargyl acetates, even
though it requires prolonged reaction time for completion. Stereointegrity of the propargylic acetate is
preserved during the hydration. The robustness of the system is successfully demonstrated through gram
scale preparation of the product in nearly quantitative yield. The common R-acyloxy methyl ketone is
transformed to 1,2-diol and 1,2-amino alcohol derivatives. Synthesis of actinopolymorphol B is achieved for
the first time involving hydration of the propargyl acetate as the key step.
Introduction
alkyne is expected to assist in the generation of either R- or β-
substituted carbonyls through hydration.3 A propargylic ester
moiety would trigger regioselective Markovnikov’s hydration of
terminal alkynes with ease, and the hydration product would
transform to R-hydroxy methyl ketones in a straightforward
manner.4 The R-hydroxy methyl ketone moieties are found in
many natural products of pharmacological significance, and
some representative molecules are shown in Figure 1.5
A straightforward and atom-economical approach to the
formation of carbonyl derivatives through alkyne hydration is
not only environmentally benign, but also cost-effective.1,2 There-
fore, hydrocarbon alkynes can be considered as pro-ketones.2 A
functional group having a directing unit adjacent to terminal
† Dedicated to Professor Tamejiro Hiyama on the occasion of his retirement
from Kyoto University, Japan.
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Dixneuf, P. H. Chem. Commun. 1997, 507.
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Published on Web 12/27/2010
DOI: 10.1021/jo101995g
r
2010 American Chemical Society

Ghosh et al.
JOCArticle
alkynes through active alkynophilic gold complexes has been
extensively investigated.10,11 Utility of cationic gold com-
plexes in alkyne hydrations has also been reported.12 For
example, terminal and internal alkynes undergo hydration in
acid-free condition when refluxed in aqueous methanol with
NaAuCl4.12o Teles,12n Hayashi and Tanaka,12m Laguna,12l
and others12a,b,e,g-k,p,q have reported the addition of metha-
nol and water to alkynes in the presence of gold catalysts and
acid promoters. Nonregioselective Au(I)-catalyzed hydra-
tion of propargylic alcohols resulted in mixtures of methyl
ketones and R,β-unsaturated aldehydes.12d,m A highly effi-
cient [(NHC)AuI]-catalyzed hydration of nonactivated alkynes
at 120 °C was demonstrated by Nolan and co-workers.12c
Survey of the gold-catalyzed hydration of alkynes reveals that
the reactions invariably require mineral acid as promoters,
higher temperature, or both.12 As these harsh conditions are
detrimental to the survival of acid-labile protecting groups, the
utility of these catalytic systems in the synthesis of complex
molecules would be limited.12 Recently, Leyva and Corma have
demonstrated the hydration of terminal alkynes at room
temperature in the presence of air-stable AuSPhosNTf2; the
reaction required 24 h for completion.12f
FIGURE 1. Examples of natural products containing R-hydroxy
methyl ketones.
Combinations of toxic mercury salts (HgO) with Brønsted
or Lewis acids (H2SO4 or BF3-OEt2 etc.) are the reagents
commonly used to perform hydration of alkynes.6 Addition
of water and oxygen-bearing nucleophiles to activated as
well as nonactivated alkynes has been carried out with use of
transition metal catalysts and acid promoters.7,8 Alkyne
hydrations in the absence of metals generally require harsh
conditions.9 Addition of oxygen-bearing nucleophiles to
This scenario has prompted us to envisage an alternative
strategy for the efficient hydration of alkynes keeping in view
the following significant aspects: (1) use of commercially
available and air stable gold catalysts, (2) elimination of acid
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TABLE 1. Optimization of Reaction Conditionsa
entry
catalyst (mol %)
cocatalyst (mol %)
solvent (0.5 mL)
water (equiv)
time (h)
yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
5% AuCI3
5% AuCI3
5% AuBr3
5% AuCI
5% AgOAc
5% AgSbF6
5% AgSbF6
5% AgSbF6
5% AgSbF6
5% AgSbF6
5% AgSbF6
1% AgSbF6
0.1% AgSbF6
2% AgOTf
2% AgBF4
2% AgOOCCF3
Nil
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
CH2CI2
MeOH
3
3
3
3
3
5
2
3
3
3
3
3
3
3
3
3
3
36
36
36
36
3
4
7
8
70
28
22
36
36
36
24
36
36
<5b
60b
30b
10b
97c
93c
92c
97c
89c
90b
85b
15b
NR
NR
63b
37b
NR
5% Ph3PAuCI
5% Ph3PAuCI
5% Ph3PAuCI
1% Ph3PAuCI
0.1% Ph3PAuCI
2% Ph3PAuCI
2% Ph3PAuCI
2% Ph3PAuCI
5% Ph3PAuCI
Nil
5% AgSbF6
1% AgSbF6
1% AgSbF6
1% AgSbF6
1% Ph3PAuCI
1% Ph3PAuCI
1% Ph3PAuCI
DMF/DMSO
aReactions were carried out with 1a (0.3 mmol) in solvent (0.5 mL) at rt. bNMR yield. cIsolated yield.
of acid-labile protecting units with broad functional group
compatibility,13 (5) short reaction time leading to overall
efficiency, (6) incorporation of multireactive functionalities
in the products, and (7) development of precursor molecules
for further complex synthesis. In the context of our wider
interest in discovering new gold-catalyzed transformations
of synthetic utility,11a we envisioned that a neighboring car-
bonyl group such as acetate would assist in effective and
regioselective alkyne hydrations under gold-catalysis condi-
tions. Activation of the terminal alkyne of the propargylic
acetate by gold catalysts would preferentially generate
5-membered electrophilic vinyl-gold species involving
5-exo-dig attack of the carbonyl oxygen.14 Finally, regio-
selective hydration would exclusively provide R-acyloxy methyl
ketone, creating a carbonyl group adjacent to the acetate
moiety; both functionalities would be available for further
synthetic explorations. A recent report from Xu and Hammond
describes the synthesis of γ-keto esters through regioselective
hydration of 3-alkynoates involving neighboring carbonyl
group participation.12b Moreover, gold-catalyzed transforma-
tion of propargylic acetates resulting in new and diverse
molecular entities has been investigated extensively.15 Herein
we report an operationally simple strategy for the synthesis
of a wide range of R-acyloxy methyl ketones through regio-
selective hydration of propargyl acetates using commer-
cially available Ph3PAuCl and AgSbF6 in dioxane-H2O at
ambient temperature. Furthermore, this transformation is
successfully employed to accomplish the first total synthesis of
actinopolymorphol B.
Results and Discussion
We first investigated the hydration of 1-phenylprop-2-ynyl
acetate (1a) (see Table 1). Precursor 1a was prepared in a straight-
forward three-step synthetic protocol, reacting trimethylsilyl acet-
ylide with benzaldehyde followed by desilylation and acetylation of
the -OH group, in overall 52% yield; isolation of respective
intermediates was avoided (see the Supporting Information).
Following this procedure, other key synthetic precursors 1 are pre-
pared in gram quantities with appreciable yields (see the Support-
ing Information).
Reaction Optimization. To start with, hydration of 1a under
different catalytic conditions comprised of gold catalysts with
silver salts, water amounts, and solvents was explored. Table 1
summarizes the results of optimization studies. Solvents dioxane
and water (3.0 equiv) are employed in this optimization study.12g
A trace amount of the desired hydration product R-acyloxy
methyl ketone (2a) was noticed when a mixture of AuCl3 and
AgOAc was used (entry 1). Interestingly, AgSbF6 salt in con-
junction with AuCl3 enhanced the product yield to 60% by
NMR (entry 2). Other silver salts, such as AgOTf, AgBF4, and
AgNO3, in combination with AuCl3 were ineffective. It appears
that the weakly coordinating SbF6- counteranion generates the
active gold-cationic species with ease and activates the alkyne
efficiently.10d,j Therefore, exploration of various combinations of
gold catalysts with AgSbF6 were surveyed: AuBr3 and AuCl were
not effective (entries 3 and 4), whereas Ph3PAuCl was found to be
the best (entry 5). With selective catalysts [Ph3PAuCl (5 mol %) and
AgSbF6 (5 mol %)] in hand, the amount of water required in this
hydration reaction was then pursued. Whereas 3 equiv of water
appeared adequate and furnished the desired product in 97%
isolated yield within 3 h (entry 5), use of smaller or larger amounts
(13) (a) Green, T. W.; Wuts, P. G. M. Protective Groups in Organic
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S. P. Angew. Chem., Int. Ed. 2006, 45, 3647. (f) Wang, S.; Zhang, L. J. Am.
Chem. Soc. 2006, 128, 8414. (g) Buzas, A.; Gagosz, F. J. Am. Chem. Soc.
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502 J. Org. Chem. Vol. 76, No. 2, 2011

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TABLE 3. Effect of Electronic Substitution on Aryl Derivatives in
Propargylic Positiona,b
TABLE 2. Effect of Directing Groupa
entry
3/1a
R
time (h)
4/2a
yield (%)
1
2
3
4
5
6
7
8
9
10
3a
3b
3c
1a
3d
3e
3f
3g
3h
3i
H
24
10
8
4a
4b
4c
2a
4d
4e
4f
4g
4h
4i
NR
70b
pivaloyl
benzoyl
acetyl
Boc
Cbz
tosyl
MOM
Me
SiMe3
78b
8
97b
24
24
10
8
24
24
NR
NR
NR
NR
NR
NRc
aReactions were carried out with 3 (1.0 mmol), Ph3PAuCl (1 mol %),
AgSbF6 (1 mol %), and water (3.0 mmol) in 1,4-dioxane (1.5 mL) at
room temperature. bIsolated yield. cCleavage of O-TMS protecting
group was observed.
of water (2 and 5 equiv) did not affect the product yield even though
slightly longer reaction time was required for completion (entries 6
and 7). We next evaluate the amount of catalyst needed in this
reaction. Lower amounts of the catalysts loading from 5 to 1 mol %
of Ph3PAuCl and AgSbF6 did not affect the reaction efficiency
(entry 8) and resulted in the hydration product 2a exclusively in 97%
isolated yield. Extended reaction time (∼3 days) was necessary to
obtain a satisfactory yield of 2a when Ph3PAuCl (0.1 mol %) and
AgSbF6 (0.1 mol %) were used (entry 9). Even though the com-
bination of Ph3PAuCl with AgOTf or AgBF4 provided the desired
hydration product in good yield (by NMR), the reaction required
∼24 h for completion (entries 10 and 11). A mixture of Ph3PAuCl
with AgOOCCF3 appeared ineffective (entry 12); AgOAc and
AgNO3 were poor. The absence of either Ph3PAuCl or AgSbF6
did not produce 2a (entries 13 and 14). Exploration of other solvents
such as CH2Cl2 and MeOH resulted in lower amounts of 2a (entries
15 and 16), whereas DMF and DMSO completely failed the
reaction (entry 17). Dioxane appears effective among other solvents
screened. The interesting disclosure from Nolan’s group describes
the synthesis of R,β-unsaturated aldehyde through regioselective
hydration of phenyl-substituted propargyl acetate 1a with [(NHC)-
AuCl], AgSbF6 in THF-H2O at 60 °C.12j In contrast, alkyne
hydration of 1a under our optimized condition exclusively delivers
R-acyloxy methyl ketone 2a (see the Supporting Information for the
spectral data). Not even a trace of R,β-unsaturated aldehyde pro-
duct was detected by the 1H NMR spectrum of the crude reaction
mixture. These results show that hydration of 1a under different
reaction conditions provides two distinct products.
Directing Group. Optimization studies reveal that hydration
of 1a effectively proceeds at ambient temperature. Presumably,
the acetyl group in 1a plays a crucial role in this hydration reaction.
The effect of another directing group on the O-propargyl alcohol
was then surveyed (Table 2). As shown in entry 1, terminal alkyne
did not undergo hydration in the absence of directing group under
the optimized catalytic condition [Ph3PAuCl (1 mol %), AgSbF6
(1 mol %), water (3.0 equiv) in 1,4-dioxane]. Pivaloyl- and benzoyl-
protected propargylic esters (3b and 3c) furnished the corresponding
products 4b and 4c, respectively, in moderate yields (entries 2 and 3),
whereas the O-protected propargyl acetate afforded the desired
hydration product 2a in 97% isolated yield (entry 4). We assume
that the bulky group hinders the attack of H2O to the reactive
intermediate participating in the reaction. Protecting groups such as
Boc, Cbz, and Ts on the -OH failed to provide the correspond-
ing hydration products (entries 5-7) even with prolonged reaction
time. Fortunately, the catalytic conditions did not cleave these
aReactions were carried out with 1 (1.0 mmol), Ph3PAuCl (1 mol %),
AgSbF6 (1 mol %), and water (3.0 mmol) in 1,4-dioxane (1.5 mL) at
room temperature. bIsolated yields.
O-protecting moieties. MOM- and methyl-protected propargyl
ethers are inert to the present catalytic system; formation of keto-
compounds through alkyne hydration was ineffective (entries 8
and 9). Survival of Boc and MOM protecting groups testifies to
the mildness of the reaction condition. However, this catalytic system
cleaved the O-TMS protecting group of 3i and afforded 3a instead
of the desired hydration product 4i (entry 10).
Reaction Scope. The optimal reaction condition [Ph3PAuCl
(1 mol %), AgSbF6 (1 mol %), water (3.0 equiv) in 1,4-dioxane]
is surveyed to investigate the generality of the hydration of the
terminal alkyne of the propargyl acetates at ambient tempera-
ture. The effect of the electronic groups on the aryl moiety of
1-phenylprop-2-ynyl acetate (1a) to the hydration reaction was
explored at first (Table 3). As observed in the optimization
reaction, the electronically neutral species reacted efficiently to
provide the hydrated product 2a in 97% isolated yield. Electron-
withdrawing groups on the aryl moiety did not affect the
product yields (2b-d); halo groups are inert to the reaction
conditions. The reaction proceeded effectively in the presence of
two chloro groups on the aromatic ring (2e). These halo groups
are the useful entities amenable to further manipulations by the
transition metal-catalyzed cross-coupling strategies. Generally,
formyl group actively participated in the gold-catalyzed trans-
formations.16 Under this catalytic condition, formyl function-
ality was well-tolerated and the desired product 2f was obtained
in 88% yield. Methyl, methoxy, and phenoxy groups at the
4- and/or 3-positions on the electron-rich aromatic ring gave
the desired products in excellent yields (2g-i). The presence of
the free -OH group on the aromatic ring did not affect the
alkyne hydration (2j).
(16) (a) Skouta, R.; Li, C. Synlett 2007, 1759. (b) Yao, X.; Li, C.-J. Org.
Lett. 2006, 8, 1953.
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TABLE 4. Effect of Ortho-Substituted and Heteroaryls in the
Propargylic Positiona,b
TABLE 5. Gold-Catalyzed Hydration of Hindered 1-Ethynyl-10,
100-alkyl/aryl/H-Substituted Acetatesa,b
aReactions were carried out with 1 (1.0 mmol), Ph3PAuCl (1 mol %),
AgSbF6 (1 mol %), and water (3.0 mmol) in 1,4-dioxane (1.5 mL) at
room temperature. bIsolated yields.
unambiguously elucidated the structure of 2w (see the Support-
ing Information). Our experimental results reveal that electronic
and steric effect on the aromatic ring did not impart the
pronounced effect to alkyne hydrations. Next, the effect of
heteroaryls in the hydration of terminal alkynes of propargyl
acetate was investigated. Intramolecular coordination of the
heteroatom to the gold-alkyne-activated species is a well-
known phenomenon.17 Therefore, we speculate that the hetero-
aryls in the propargyl acetate may hinder the hydration of the
triple bond. To probe our assumption, hydration of thienyl-2-
substituted propargyl acetate (1x) was performed under the
optimized condition and the corresponding hydration product
2x resulted in 75% yield in 2 h. Unfortunately, furyl-2-substi-
tuted propargyl acetate failed to provide the desired ketone; a
complex reaction profile was observed with the consumption of
starting propargyl acetate. In the case of N-methyl indole
derivative, the hydration reaction did not proceed, whereas
N-benzoyl-protected indole-2-susbtituted propargyl acetate (1y)
provided the corresponding hydration product 2y in 78% yield.
We believe that the lone pair electron on nitrogen in N-methyl
indole inhibits the activity of the cationic gold species through
coordination; in contrast, the stabilization of the lone pair
electron on nitrogen in 2y led to the hydration product.
Formation of R-acyloxy methyl ketones through regioselec-
tive hydration of the terminal alkynes of the aryl- and hetero-
aryl-substituted propargyl acetates has been successfully demon-
strated. Next, we turned our attention to assess the effect of alkyl,
dialkyl, and aryl-alkyl groups at the propargylic position to the
alkyne hydration and the results are detailed in Table 5. When
n-hexyl- and benzyl-substituted propargyl acetates are subjected to
the optimized condition, the corresponding hydration products 2z
and 2aa are obtained in excellent yields. Although Nolan observed
the formation of R,β-unsaturated aldehyde through regioselective
hydration of benzyl-substituted propargyl acetate 1aa under
[(NHC)AuCl], AgSbF6 in THF-H2O at 60 °C,12j our optimized
condition exclusively delivered R-acyloxy methyl ketone 2aa from
1aa. The bromo group on the alkyl chain survived under the
catalytic system and the product 2ab resulted in 86% yield;
further manipulation of the bromo group would deliver valuable
building blocks. Deprotection of acid-labile -OTHP ethers gene-
rally occurs under aqueous Lewis acids at ambient temperature.13
aReactions were carried out with 1 (1.0 mmol), Ph3PAuCl (1 mol %),
AgSbF6 (1 mol %), and water (3.0 mmol) in 1,4-dioxane (1.5 mL) at
room temperature. bIsolated yields.
Functional group manipulations are the tools used in the
fabrication of a complex molecular framework. It is therefore
important to examine the relative stability of the protecting
groups under this catalytic condition. Protecting groups of the
hydroxyl moiety are generally sensitive to the mild acidic and
basic reagents. Thus, investigation of the acid labile silyl ethers
to the optimized catalytic condition pursued. As observed pre-
viously, the reaction condition cleaved the mildest -OTMS group
(Table 2, entry 9). Gratifyingly, the bulkier silyl protecting groups
such as -TBDPS (tert-butyldiphenylsilyl) and -OTBS (t-butyl-
dimethylsilyl) survived and the desired keto compounds 2k, and
2l were isolated in 81% and 80% yields, respectively. In con-
trast, gold catalyst (AuSPhosNTf2) used in the hydration of the
triple bond showed partial stability to the robust TBDPS group,
reported by Leyva and Corma.12f It appears that the present cata-
lytic condition is milder than the previously reported systems.12
Furthermore, more electron-rich substrate 1m undergoes hydration
efficiently within 2 h to afford 2m in 91% yield.
The effect of ortho-substitution on the aryl moiety was next
examined, and the results are shown in Table 4. Hydration of the
terminal triple bond proceeded smoothly in the presence of
electron-poor ortho substituent, such as chloro and bromo
groups, on the aromatic ring of propargyl acetates (1n-q)
producing the corresponding ketones (2n-q) in excellent yields.
Similarly, 1-(naphthalen-1-yl)prop-2-ynyl acetate (1r) under-
went hydration efficiently, affording 95% yield of 2r. The
methyl group at the 2-position did not inhibit hydration and
delivered 2s in 92% yield. The o-O-allyl group did not partici-
pate in the hydration and the desired product 2t was isolated in
96% yield; the allyl functionality could be useful for further
synthetic elaboration. The required ketone 2u was successfully
obtained from the anthracene-based propargyl acetate. More
sterically demanding substrates having two ortho-substitutions
on the aryl moiety underwent efficient hydration under the
optimized condition and the desired products 2v and 2w are
obtained in excellent yields. X-ray crystallographic analysis
(17) (a) Hashmi, A. S. K.; Rudolph, M.; Bats, J. W.; Frey, W.; Rominger, F.;
Oeser, T. Chem.—Eur. J. 2008, 14, 6672. (b) Hashmi, A. S. K.; Kurpejojovic, E.;
€
Frey, W.; Bats, J. W. Tetrahedron 2007, 63, 5879. (c) Hashmi, A. S. K.; Wolfle,
M.; Ata, F.; M, H.; Sꢀalate, R.; Frew, W. Adv. Synth. Catal. 2006, 348, 2501.
504 J. Org. Chem. Vol. 76, No. 2, 2011

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TABLE 7. Hydration of TMS-Substituted Propargyl Acetatea
TABLE 6. Gold-Catalyzed Hydration of 1-Ethynylcycloalkyl Acetatesa,b
aReactions were carried out with 1 (1.0 mmol), Ph3PAuCl (1 mol %),
AgSbF6 (1 mol %), and water (3.0 mmol) in 1,4-dioxane (1.5 mL) at
room temperature. bIsolated yields.
Surprisingly, the -OTHP protecting group was well-tolerated
in this gold-catalyzed hydration protocol, and the product 2ac
was isolated in 78% yield; this observation demonstrates the mild
nature of the catalytic conditions. Unactivated sterically hindered
propargyl acetate such as 1ad having a quaternary R-carbon center
with two alkyl substituents did not affect the reaction efficiency and
delivered the product 2ad in 94% yield under the optimized
condition. Similarly, both methyl- and aryl-substituted propargyl
acetates 1ae and 1af effectively underwent hydration to furnish the
desired R-acyloxy-R0,R00-disubstituted methyl ketones 2ae and 2af
in good yields.
aReactions were carried out with 5 (1.0 mmol), Ph3PAuCl (1 mol %),
AgSbF6 (1 mol %), and water (5.0 mmol) in 1,4-dioxane (1.5 mL) at
room temperature. bIsolated yields. c1H NMR yields.
SCHEME 1. Hydration of Chiral Propargyl Acetate
To further expand the scope of the reaction, exploration of
hindered 1-ethynylcycloalkyl acetates to the alkyne hydrations was
pursued and the results are shown in Table 6. Excellent yields of the
desired R-acyloxy methyl ketones (2ag-2ai) were attained in the
hydration of sterically demanding cyclic-substituted propargyl
acetates under the optimized condition; different rings (5-, 6-, or
7-membered) did not interfere in the reaction efficiency. The 1,3-
dioxolane is the most widely carbonyl protective moiety used in
organic synthesis.13 Acid-catalyzed hydrolysis and oxidation easily
cleaves the 1,3-dioxolanes.13 Gold-catalyzed hydration of com-
pound 1aj having both the propargyl acetate and the acid-sensitive
1,3-dioxolane moieties affords the product 2aj in 80% yield.
Gratifyingly, the ketal protecting moiety survived under this
catalytic condition; this observation once again proved the mildest
nature of the catalysts.
Deprotection of trimethylsilyl ether under the optimized
catalytic condition was previously observed (Table 2, entry 9).
Leyva and Corma have shown the cleavage of the alkynyl
C-TMS group by AuSPhosNTf2.12f Unfortunately, TMS-
containing alkyne failed to react with the Nolan’s condition at
an elevated temperature.12j These observations motivated us to
investigate the hydration of alkynyl-TMS-protected propargyl
acetates under the optimized catalytic condition and the results
are summarized in Table 7. Thus, the gold-catalyzed hydration
of alkynyl-TMS-protected phenyl propargyl acetates 5a pro-
vided R-acyloxy methyl ketone 2a in 82% yield, even though
it requires prolonged reaction time (∼20 h) for completion
(Table 7, entry 1). It appears that the catalytic conditions cleave
the alkyne C-TMS bond at first followed by the hydration of
the terminal alkyne of the propargyl acetate. Similar results
are also obtained in the case of 4-bromophenyl- and benzyl-
substituted TMS-containing propargyl acetates 5d and 5aa
(Table 7, entries 2 and 6). In a few other cases, a mixture of
desilylated as well as the hydration products is observed even
though the reaction continued for 24 h (entries 3, 4, and 7).
Reaction of thienyl-2-substituted TMS-containing propargyl
acetates 5x under the catalytic conditions resulted in desilylated
product 1x in 59% yield by NMR without producing the
required R-acyloxy methyl ketone 2x; incomplete conversion
of 5x was noticed even with the extended reaction time. These
observations reveal that TMS-containing propargyl acetates are
not effective in this hydration reaction.
Next, we examined the effect of the catalytic conditions on the
hydration of the chiral propargylic acetate (Scheme 1). Follow-
ing the reported procedure,18a the optically active (R)-1-phenyl-
prop-2-ynyl acetate (7) was prepared with 76% ee (determined by
chiral HPLC; see the SI). The optical rotation of (R)-7 agrees with
the literature value.18b Hydration of (R)-7 was carried out by using
the optimized catalytic condition, and the product (S)-8 was
obtained in 92% yield with 76% ee (determined by chiral HPLC,
Scheme 1; see the SI). Optical rotation analysis confirms that the
chiral center of the acetate moiety did not racemize during the gold-
catalyzed hydration of the triple bond (Scheme 1; see the SI).
Therefore, we believe that this protocol would allow the synthesis
of optically active R-acyloxy methyl ketones that would finally lead
to enantio-enriched R-hydroxy methyl ketones in simple synthetic
operations.
The robustness of the catalytic conditions is demonstrated
through gram scale synthesis of the hydration products. Screen-
ing of different amounts of catalyst mixtures containing Ph3-
PAuCl and AgSbF6 (0.1 or 0.3 mol %) to the hydration of 1a
(10 mmol) was performed. A sluggish reaction profile was ob-
served when 0.1 mol % of gold and silver catalysts is employed.
However, hydration of 1a successfully completed within appre-
ciable time (∼20 h) in the presence of 0.3 mol % of gold and
silver catalysts. Under this modified catalytic condition, pro-
ducts 2a and 2c are obtained directly by filtering the crude
reaction mixtures through a small pad of Celite, in 94% and
95% yields, respectively (Scheme 2).
Reduction of both the keto and acetate moieties of R-acyloxy
methyl ketones would furnish 1,2-disubstituted glycol derivatives,
(18) (a) Yang, F.; Xi, P.; Yang, L.; Lan, J.; Xie, R.; You, J. J. Org. Chem.
2007, 72, 5457. (b) Waldinger, C.; Schneider, M.; Botta, M.; Corelli, F.;
Summa, V. Tetrahedron: Asymmetry 1996, 7, 1485.
J. Org. Chem. Vol. 76, No. 2, 2011 505

Ghosh et al.
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SCHEME 2. Gram Scale Synthesis of R-Acyloxy Methyl
Ketones
FIGURE 2. Kurasoin B, sattazoline, and actinopolymorphol B
classes of natural products having similar structural morphology.
our synthetic approach provides a simple route to access R-acyloxy
methyl ketone moiety with broad substrate scope under mild
reaction conditions, we aimed for the synthesis of actinopolymor-
phol B involving the efficient gold-catalyzed intermolecular hydra-
tion of propargyl acetate at room temperature.
SCHEME 3. Synthesis of 1,2-Glycol and 1,2-Amino Alcohol
The campaign for the synthesis of actinopolymorphol B
(Scheme 4) was initiated from commercially available indole-
3-acetic acid (11). Esterification followed by N-Boc protection f 11
provided 12 in 86% overall yield. Access to preparing a large
quantity of the known aldehyde 14 was found to be critical since
DIBAL-H reduction of ester 12 produced 14 in only 37% yield.25
Therefore, a two-step synthetic protocol involving reduction and
oxidation sequences was considered. To reduce 12 effectively,
various reducing agents were surveyed under different reaction
conditions. Gratifyingly, reduction of ester with LiAlH4 at -78 °C
was found productive and resulted in 13 in 92% isolated yield.
Formation of unwanted side products are observed during the
oxidation of 13 under Dess-Martin and Swern conditions. Oxida-
tion of 13 with [bis(acetoxy)iodo]benzene (BAIB) in the presence of
TEMPO led to aldehyde 14 in only 57% yield. Addition of TMS-
acetylide to the carbonyl moiety of 14 was effectively carried out at
-78 °C and furnished 15 in 89% yield. Acetate formation (Ac2O,
DMAP, Et3N) and subsequent desilylation (TBAF) delivered the
desired propargyl acetate 16 in 83% overall yield. The starting
precursor 16 was exposed to the optimized catalytic condition
[Ph3PAuCl (1 mol %) and AgSbF6 (1 mol %)] in the presence of
H2O in 1,4-dioxane at room temperature for 7 h, and the desired
R-acyloxy methyl ketone 17 was isolated in 83% yield.26 Finally,
cleavage of N-Boc and O-acetyl of 17 would give actinopolymor-
phol B (18). At first, we investigated the deprotection of the N-Boc
of 17 while keeping the acetate moiety intact. Exploration of
established conditions involving (i) trifluoro acetic acid (TFA) in
CH2Cl2,13a (ii) TBAF refluxed in THF,13a and (iii) TMSCl in
phenol to the deprotection of the N-Boc moiety of indole 17
failed,13a whereas TMSOTf in the presence of DBU cleaved the
Boc-group successfully.27 Subsequently, base-induced deacetylation
of the crude mixture of 17-NH led to complex mixtures. Gratify-
ingly, Sc(OTf)3-catalyzed saponification of the acetate moiety
furnished 18 in 56% yield over the two-step sequence.13,28
which are useful building blocks.19 For example, lithium aluminum
hydride (LiAlH4) reduces 2a to afford 9 (dr 1.8:1) in 82% yield at
0 °C (Scheme 3, eq 1). 1,2-Amino alcohols are also valuable pre-
cursors to the chiral auxiliaries.20 Imination of 2-oxo-1-phenylpro-
pyl acetate (2a) followed by reduction with H2 in 10% Pd/C
resulted in racemic 1,2-amino alcohol 10 (dr 3:2) in overall 36%
yield (Scheme 3, eq 2).21
This methodology attests to the broad substrate scope in
tolerating functionalities and acid-sensitive protecting groups.
To prove the synthetic potential of this strategy, we embarked
on the synthesis of a natural product involving hydration of the
propargylic acetate as a key step. Recently, a series of a new class of
natural products actinopolymorphol A, B, and C were isolated
from Actinopolymorpha rutilus (YIM45725).22a Moreover, the
structural morphology of actinopolymorphol B resembles closely
that of kurasoin B and sattazolin derivatives (Figure 2).22a Kurasoin
B and its derivatives are known protein farnesyltransferase
(PFTase) inhibitors; and therefore these compounds have the
potential to show anticancer properties.22b,c Moreover, sat-
tazoline and its derivatives expressed their antiviral activity
against the Herpes simplex viruses type 1 and 2 and inhibit the
protein synthesis in Herpesvirus-infected cells selectively.23
The central core R-hydroxy ketone unit is present in the
natural products depicted in Figures 1 and 2. The potency
of the compounds (Figure 2) is believed to rely primarily in the
presence of R-hydroxy ketone core and the indole substitu-
tion; moreover, the stereochemistry of the hydroxyl functional
group also plays a critical role in exhibiting PFTase inhibition.24
We anticipate that actinopolymorphol B would be a potentially
important drug candidate such as kurasoin B and sattazoline. As
Mechanistic Studies
Experimental results show that the hydration of propargyl
acetate in dioxane and water with gold catalyst proceeds effi-
ciently at room temperature in the absence of acid promoters.
The critical role of the acetate group located adjacent to the
(19) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev.
1994, 94, 2483.
(20) (a) Airiau, E.; Girard, N.; Mann, N.; Salvadori, J.; Taddel, M. Org.
Lett. 2009, 11, 5314 and references cited therein. (b) Ager, D. J.; Prakash, I.;
Schaad, D. R. Chem. Rev. 1996, 96, 835.
(25) Ferrer, C.; Escribano-Cuesta, A.; Echavarren, A. M. Tetrahedron
2009, 65, 9015.
(21) (a) Barrett, A. G. M.; Spilling, C. D. Tetrahedron Lett. 1988, 29,
5733. (b) Neufeldt, S. R.; Sanford, M. S. Org. Lett. 2010, 12, 532. (c) Patil,
M. N.; Bhowmick, K. C.; Joshi, N. N. Tetrahedron Lett. 2010, 51, 5927.
(22) (a) Huang, S.-X.; Powel, E.; Rajski, S. R.; Zhao, L.-X.; Jiang, C.-L.;
Duan, Y.; Xu, W.; Shen, B. Org. Lett. 2010, 12, 3525 and references cited
therein. (b) Fernandes, R. A. Tetrahedron: Asymmetry 2008, 19, 15. (c)
Andrus, M. B.; Hicken, E. J.; Stephens, J. C.; Bedke, D. K. J. Org. Chem.
2006, 71, 8651.
(26) Hydration of TMS-substituted propargylic acetate of 15 was per-
formed under the optimized catalytic condition [Ph3PAuCl (1 mol %) and
AgSbF6 (1 mol %)] in the presence of H2O in 1,4-dioxane for 24 h. The
reaction did not undergo completion; the 1H NMR spectrum of the crude
reaction mixture showed the formation of 20% of hydration product 17,
24% of desilylated 16, and 51% of unreacted TMS-substituted propargylic
acetate of 15.
(23) Lampis, G.; Deidda, D.; Maullu, C.; Madeddu, M. A.; Pompei, R.;
Monache, R. D.; Satta, G. J. Antibiot. 1995, 48, 967.
(27) Bastiaans, H. M. M.; van derBaan, J. L.; Ottenheijm, H. C. J. J. Org.
Chem. 1997, 62, 3880.
(24) Sunazuka, T.; Hirose, T.; Zhi-Ming, T.; Uchida, R.; Shiomi, K.;
Harigaya, Y.; Omura, S. J. Antibiot. 1997, 50, 453.
(28) Kajihiro, H.; Mitamura, S.; Mori, A.; Hiyama, T. Tetrahedron Lett.
1999, 40, 1689.
506 J. Org. Chem. Vol. 76, No. 2, 2011

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SCHEME 4. Synthesis of Actinopolymorphol B via Hydration of Propargyl Acetatea
aReagents and conditions: (i) (a) SOCl2, MeOH, 0 to 25 °C, 4 h, (b) Boc2O, DMAP, CH2Cl2, rt, 8 h, 86% (over two steps); (ii) LiAlH4, THF, -78 °C,
45 min, 92%; (iii) BAIB, TEMPO, 0 to 25 °C, 2 h, 57%; (iv) TMS-acetylene, n-BuLi (1.6 M solution in THF), THF, -78 °C, 3 h, 89%; (v) (a) Ac2O,
DMAP, Et3N, CH2Cl2, rt, 1 h, (b) TBAF (1.0 M solution in THF), THF, 0 °C, 1 h, 83% (over two steps); (vi) Ph3PAuCl (1 mol %), AgSbF6 (1 mol %),
H2O (3.0 equiv), 1,4-dioxane, rt, 7 h, 83%; (vii) (a) TMSOTf, DBU, CH2Cl2, 0 °C to rt, 8 h, (b) Sc(OTf)3 (20 mol %), MeOH/H2O (4:1), rt, 12 h, 56%
(over two steps).
SCHEME 5. Proposed Catalytic Cycle
terminal alkyne in the regioselective hydration warrants careful
investigation.12b To probe the reaction pathway and to validate
the mode of water attack to the unsaturated bonds, oxygen-18-
enriched water is employed.29 The affinity of alkyne to cationic
gold(I) species such as [Me3PAu]þ over methanol and water
is well established.12 Thus, the reactive intermediate gold-
alkyne-π complex 19, resulting from the activation of the
alkyne 1ah by cationic gold(I)phosphine, is believed to take part
in the first step of the transformation (Scheme 5). Experimental
and theoretical studies reveal that enol ethers and ketals are the
plausible intermediates involved in the hydration of alkynes in
alcoholic solvents.11b,12 Therefore, participation of enol ether
intermediates seems unlikely as the reactions are performed in
dioxane. Hayashi, Tanaka, and the Laguna group have inde-
pendently demonstrated that the direct attack of water on the
gold-alkyne-π complex in nonalcoholic medium provides the
desired hydration product.12l,m Pathway A is proposed based on
the direct SN20 attack of H2O18 on 19 followed by protodeaura-
tion of 20 and isomerization of enol 21 leading to the ketone
22.12j,l,m Base-induced deacetylation of 22 would then generate
the desired R-hydroxy methyl ketone 23 with 18O insertion.
However, the mass spectrum of the isolated product shows no
sign of 18O insertion. On the basis of this evidence, route A
appears unlikely. The alternate route involves the stabilization
of the electrophilic gold-alkyne-π complex intermediate 19
through neighboring nucleophilic carbonyl group participation
(paths B and C, Scheme 5). The 5-exo-dig attack of carbonyl
oxygen on the γ-carbon would generate the 5-membered elec-
trophilic vinyl-gold species 24 (path B),14 whereas the 6-endo-dig
attack would provide the 6-membered intermediate 29 (path C).14
Although as per the Baldwin’s rule,2 attack of the carbonyl
oxygen on the activated alkyne is possible in both ways, the
former is preferred in the case of gold-activated terminal
alkynes.14 Involvement of such reactive intermediates in various
gold-catalyzed organic transformations is well explored.15 The
nucleophilic addition of H2O18 to 24 produces the intermediate
25 as illustrated in path B. Protodemetalation of 25 followed by
isomerization of 26 furnishes R-acyloxy methyl ketone 27 with
18O in the ester carbonyl group. Molecular mass of 27 [187
(Mþ þ 1)] confirms this; see the Supporting Information. Base-
catalyzed deacetylation of 27 produces the corresponding
R-hydroxy methyl ketone 28 [143 (Mþ þ 1)] with the loss of 18O.
This observation clearly demonstrates that the rupture of the
unsaturated bond leading to C-O bond formation is possible
(29) Li, Y.; Song, D.; Dong, V. J. Am. Chem. Soc. 2008, 130, 2962.
J. Org. Chem. Vol. 76, No. 2, 2011 507

Ghosh et al.
JOCArticle
only through the intramolecular assistance of the carbonyl
oxygen of the acetate moiety. The acetate moiety is regained
through the subsequent attack of a water molecule. Attack of
H218O on 29 would generate aldehyde products (30 or 31) as
depicted in path C; however, such products were never observed.
This proves unambiguously that the regioselective hydration
product resulted exclusively from the 5-exo-dig cyclized reactive
intermediate 24 under the optimal conditions shown in path B,
Scheme 5.
165 (12), 147 (10), 133 (100), 105 (10), 74 (6). Anal. Calcd for
C11H12O3: C, 68.74; H, 6.29. Found: C, 68.85; H, 6.19.
1-(4-Fluorophenyl)-2-oxopropyl acetate (2b): 193 mg, 92%
yield; colorless oil; Rf 0.31 (6:1 hexane/EtOAc); 1H NMR (400
MHz, CDCl3) δ 7.44-7.34 (m, 2H), 7.15-7.04 (m, 2H), 5.95 (s,
1H), 2.19 (s, 3H), 2.11 (s, 3H); 13C NMR (101 MHz, CDCl3) δ
201.6, 170.2, 164.5, 162.0, 129.97, 129.89, 129.0, 116.2, 116.0,
80.0, 26.1, 20.6; 19F NMR (376 MHz, CDCl3) δ -111.70; IR
(neat) νmax 2937, 1743, 1732, 1606, 1510, 1373, 1228, 1051 cm-1
;
MS (EI) m/z (%) 211 (Mþ þ 1, 100), 197 (5), 167 (10). Anal.
Calcd for C11H11FO3: C, 62.85; H, 5.27. Found: C, 62.78;
H, 5.31.
Conclusion
We have shown that the commercially available catalyst
[Ph3PAuCl and AgSbF6] in dioxane-H2O efficiently hy-
drates a wide range of readily accessible propargyl acetates
under ambient temperature. This strategy allows the efficient
synthesis of an array of R-acyloxy methyl ketones in good to
excellent yields. The highlights of this strategy are as follows:
(a) the mild reaction conditions, (b) operationally simple and
easy to handle reagents, (c) absence of acidic promoters,
(d) broad functional group compatibility and tolerance to acid-
labile protecting groups, (e) short reaction times, (f) gram
scale synthesis, (g) isolation of products through simple
filtration and easy purification, and (h) retention of chirality
of the acetate moiety. The method developed is useful in the
conversion of directed monofunctionality to reactive bifunc-
tionality that finally leads to the generation of R-hydroxy
ketones,4 which are indeed synthetically versatile intermedi-
ates for various biologically active compounds.5 This proto-
col also allows the introduction of the key R-hydroxy methyl
ketone group in actinopolymorphol B (18).22a The first total
synthesis of 18 is accomplished through a 7-step route, in
16% overall yield, starting from commercially available
indole-3-acetic acid. On the basis of an 18O-labeling study,
the reaction is proposed to proceed through the addition of
water to the favored 5-exo-dig cyclized intermediate. On-
going research activities in our group are directed toward
discovering the asymmetric variant of this reaction, finding
efficient strategy to the regioselective hydration of internal
alkynes, and exploring the total synthesis of natural products
of pharmaceutical interest.
1-(4-Chlorophenyl)-2-oxopropyl acetate (2c): 213 mg, 94%
yield; colorless oil; Rf 0.50 (10:1 hexane/EtOAc); 1H NMR
(400 MHz, CDCl3) δ 7.59-7.52 (m, 2H), 7.35-7.27 (m, 2H),
5.94 (s, 1H), 2.21 (s, 3H), 2.14 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 201.3, 170.1, 132.29, 132.25, 129.6, 123.7, 80.2, 26.1,
20.7; IR (neat) νmax 2930, 1736, 1731, 1371, 1232, 1053 cm-1
;
MS (EI) m/z (%) 229 (Mþ þ 2, 37), 227 (Mþ, 100), 213 (18), 209
(45), 185 (11), 167 (66), 139 (18). Anal. Calcd for C11H11ClO3: C,
58.29; H, 4.89. Found: C, 58.41; H, 4.85.
1-(4-Bromophenyl)-2-oxopropyl acetate (2d): 241 mg, 89%
yield; pale yellow oil; Rf 0.55 (10:1 hexane/EtOAc); H NMR
1
(400 MHz, CDCl3) δ 7.54 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.0
Hz, 2H), 5.92 (s, 1H), 2.19 (s, 3H), 2.11 (s, 3H); 13C NMR (101
MHz, CDCl3) δ 201.3, 170.1, 132.3, 129.6, 123.7, 80.2, 26.1,
20.7; IR (neat) νmax 2930, 1749, 1732, 1371, 1487, 1371, 1232,
1053 cm-1; MS (EI) m/z (%) 273 (Mþ þ 2, 100), 272 (Mþ þ 1, 8),
271 (Mþ, 97), 253 (41), 231 (11), 211 (38), 183 (5), 146 (13), 132
(19). Anal. Calcd for C11H11BrO3: C, 48.73; H, 4.09. Found: C,
48.65; H, 4.13.
1-(3,4-Dichlorophenyl)-2-oxopropyl acetate (2e): 250 mg, 96%
yield; pale yellow oil; Rf 0.31 (8:1 hexane/EtOAc); 1H NMR (400
MHz, CDCl3) δ 7.52 (s, 1H), 7.48 (d, J = 8.4 Hz, 1H), 7.25 (d,
J = 8.0 Hz, 1H), 5.89 (s, 1H), 2.20 (s, 3H), 2.14 (s, 3H); 13C
NMR (101 MHz, CDCl3) δ 201.1, 169.9, 133.7, 133.4, 131.0,
129.8, 127.1, 79.4, 26.1, 20.6; IR (neat) νmax 2930, 1749, 1732,
1487, 1371, 1236, 1062 cm-1; MS (EI) m/z (%) 263 (Mþ þ 2, 60),
261 (Mþ, 100), 215 (39), 201 (37), 181 (79), 149 (21). Anal. Calcd
for C11H10Cl2O3: C, 50.60; H, 3.86. Found: C, 50.66; H, 3.90.
1-(4-Formylphenyl)-2-oxopropyl acetate (2f): 193 mg, 88%
yield; colorless oil; Rf 0.33 (4:1 hexane/EtOAc); 1H NMR (400
MHz, CDCl3) δ 10.03 (s, 1H), 7.92 (d, J = 8.0 Hz, 2H), 7.61 (d,
J = 8.0 Hz, 2H), 6.03 (s, 1H), 2.22 (s, 3H), 2.15 (s, 3H); 13C
NMR (101 MHz, CDCl3) δ 201.1, 191.5, 169.9, 139.5, 136.8,
130.2, 128.3, 80.3, 26.1, 20.6; IR (neat) νmax 3011, 1745, 1730,
1695, 1425, 1371, 1234, 1053 cm-1; MS(EI) m/z (%) 223(Mþ þ 2,
18), 193 (46), 161 (100), 105 (11). Anal. Calcd for C12H12O4: C,
65.45; H, 5.49. Found: C, 65.32; H, 5.41.
Experimental Section
General Procedure for the Gold-Catalyzed Hydration of Pro-
pargyl Acetates (1). A mixture of Ph3PAuCl (4.9 mg, 0.01 mmol)
and AgSbF6 (3.4 mg, 0.01 mmol) in dioxane (1.5 mL) was stirred
in a Schlenk flask under an argon atmosphere for 30 min at
ambient temperature. This freshly prepared light pink gold-
silver complex mixture was introduced to the Schlenk flask
having 1 (1.0 mmol) followed by the addition of deionized water
(54 μL, 3.0 mmol) at ambient temperature. The resulting reac-
tion mixture was stirred for the time shown in the respective
tables at ambient temperature. Upon complete consumption
of starting precursor, the reaction mixture was diluted with
dichloromethane (10 mL) and filtered over a small pad of Celite.
The solvent was evaporated under reduced pressure and the
crude reaction mixture was purified by using column chroma-
tography on silica gel.
2-Oxo-1-phenylpropyl acetate (2a): 186 mg, 97% yield; color-
less oil; Rf 0.38 (10:1 hexane/EtOAc); 1H NMR (400 MHz,
CDCl3) δ 7.42 (br s, 5H), 5.99 (s, 1H), 2.21 (s, 3H), 2.13 (s, 3H);
13C NMR (101 MHz, CDCl3) δ 201.7, 170.3, 133.2, 129.4, 129.1,
128.1, 80.9, 26.1, 20.7; IR (neat) νmax 2601, 1745, 1730, 1372,
1232, 1049 cm-1; MS (EI) m/z (%) 193 (Mþ þ 1, 70), 179 (16),
2-Oxo-1-p-tolylpropyl acetate (2g): 196 mg, 95% yield; color-
less oil; Rf 0.54 (10:1 hexane/EtOAc); 1H NMR (400 MHz,
CDCl3) δ 7.29 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 5.95
(s, 1H), 2.37 (s, 3H), 2.18 (s, 3H), 2.10 (s, 3H); 13C NMR (101
MHz, CDCl3) δ 201.8, 170.4, 139.5, 130.2, 129.8, 128.1, 80.8,
26.1, 21.2, 20.7; IR (neat) νmax 3028, 1745, 1732, 1429, 1371,
1235, 1049 cm-1; MS (EI) m/z (%) 207 (Mþ þ 1, 32), 188 (14),
177 (22), 161 (14), 147 (100), 135 (12), 119 (14). Anal. Calcd for
C12H14O3: C, 69.88; H, 6.84. Found: C, 69.75; H, 6.92.
1-(3-Methoxyphenyl)-2-oxopropyl acetate (2h): 202 mg, 91%
yield; pale yellow oil; Rf 0.29 (10:1 hexane/EtOAc); H NMR
1
(400 MHz, CDCl3) δ 7.35-7.27 (m, 1H), 7.00 (d, J = 7.6 Hz,
1H), 6.96-6.88 (m, 2H), 5.94 (s, 1H), 3.81 (s, 3H), 2.19 (s, 3H),
2.11 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 201.5, 170.2, 159.9,
134.4, 130.1, 120.3, 114.9, 113.3, 80.8, 55.3, 26.0, 20.6; IR (neat)
ν
max 2941, 1747, 1732, 1602, 1489, 1373, 1236, 1045 cm-1; MS
(EI) m/z (%) 223 (Mþ þ 1, 22), 209 (13), 195 (9), 177 (11), 163
(100), 135 (13). Anal. Calcd for C12H14O4: C, 64.85; H, 6.35.
Found: C, 64.91; H, 6.41.
508 J. Org. Chem. Vol. 76, No. 2, 2011

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2-Oxo-1-(3-phenoxyphenyl)propyl acetate (2i): 247 mg, 87%
yield; pale yellow oil; Rf 0.35 (6:1 hexane/EtOAc); 1H NMR (400
MHz, CDCl3) δ 7.36 (br t, J = 7.2 Hz, 3H), 7.15 (br t, J = 7.2
Hz, 2H), 7.09 (s, 1H), 7.05-6.97 (m, 3H), 5.93 (s, 1H), 2.19 (s,
3H), 2.13 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 201.4, 170.1,
157.9, 156.4, 134.9, 130.3, 129.9, 123.8, 122.4, 119.1, 118.1, 80.5,
26.1, 20.7; IR (neat) νmax 3065, 1747, 1730, 1585, 1444, 1373,
1238, 1053 cm-1; MS (EI) m/z (%) 285 (Mþ þ 1, 100), 243 (13).
Anal. Calcd for C17H16O4: C, 71.82; H, 5.67. Found: C, 71.92;
H, 5.59.
129.8, 128.1, 124.3, 79.2, 26.8, 20.6; IR (neat) νmax 2926, 1749,
1732, 1568, 1471, 1371, 1228, 1028 cm-1; MS (EI) m/z (%) 294
(Mþ þ Na, 64), 273 (Mþ þ 2, 17), 271 (Mþ, 19), 245 (13), 211
(21), 181 (10), 149 (100), 131 (23), 103 (3). Anal. Calcd for
C11H11BrO3: C, 48.73; H, 4.09. Found: C, 48.81; H, 4.13.
1-(2,4-Dichlorophenyl)-2-oxopropyl acetate (2p): 245 mg,
94% yield; pale yellow oil; Rf 0.48 (8:1 hexane/EtOAc); 1H
NMR (400 MHz, CDCl3) δ 7.48 (s, 1H), 7.37-7.25 (m, 2H), 6.44
(s, 1H), 2.18 (s, 3H), 2.17 (s, 3H); 13C NMR (101 MHz, CDCl3) δ
200.4, 169.8, 133.9, 133.8, 132.4, 131.3, 127.9, 77.2, 26.8, 20.5;
IR (neat) νmax 3080, 2924, 1757, 1738, 1566, 1475, 1371, 1228,
1043 cm-1; MS (EI) m/z (%) 263 (Mþ þ 2, 3), 262 (Mþ þ 1, 13),
261 (Mþ, 100), 259 (16), 247 (25). Anal. Calcd for C11H10Cl2O3:
C, 50.60; H, 3.86. Found: C, 50.65; H, 3.82.
1-(2,3-Dichlorophenyl)-2-oxopropyl acetate (2q): 246 mg,
94% yield; colorless oil; Rf 0.35 (10:1 hexane/EtOAc); 1H
NMR (400 MHz, CDCl3) δ 7.53 (dd, J=2.0, 8.0 Hz, 1H),
7.33 (dd, J = 2.0, 8.0 Hz, 1H), 7.31-7.25 (m, 1H), 6.56 (s, 1H),
2.21 (s, 3H), 2.20 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 200.4,
169.8, 133.9, 133.9, 132.4, 131.3, 127.9, 127.8, 77.2, 26.8, 20.5;
IR (neat) νmax 2926, 1747, 1732, 1566, 1454, 1371, 1228, 1060
cm-1; MS (EI) m/z (%) 265 (Mþ þ 4, 38), 263 (Mþ þ 2, 40), 261
(Mþ, 48), 235 (19), 201 (61), 183 (100), 181 (21), 147 (19), 81 (6).
Anal. Calcd for C11H10Cl2O3: C, 50.60; H, 3.86. Found: C,
50.51; H, 3.92.
1-(3-Hydroxyphenyl)-2-oxopropyl acetate (2j): 176 mg, 85%
yield; colorless oil; Rf 0.40 (3:1 hexane/EtOAc); 1H NMR (400
MHz, CDCl3) δ 7.32-7.24 (m, 1H), 6.97 (d, J = 7.6 Hz, 1H),
6.89 (br s, 2H), 6.42-6.23 (br s, 1H, for -OH), 5.95 (s, 1H), 2.18
(s, 3H), 2.14 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 202.9,
170.7, 156.7, 134.3, 130.5, 120.2, 116.8, 114.7, 80.8, 26.2, 20.7;
IR (neat) νmax 3412, 1749, 1728, 1456, 1373, 1240, 1051 cm-1
;
MS (EI) m/z (%) 209 (Mþ þ 1, 78), 181 (11), 149 (100), 121 (9),
79 (9). Anal. Calcd for C11H12O4: C, 63.45; H, 5.81. Found: C,
63.32; H, 5.86.
1-(3-(tert-Butyldiphenylsilyloxy)phenyl)-2-oxopropyl acetate
(2k): 362 mg, 81% yield; pale brown oil; Rf 0.56 (10:1 hexane/
EtOAc); 1H NMR (400 MHz, CDCl3) δ 7.70 (br t, J = 7.2 Hz,
4H), 7.47-7.33 (m, 6H), 7.13 (t, J = 7.6 Hz, 1H), 6.91 (d, J = 7.6
Hz, 1H), 6.79 (d, J = 7.6 Hz, 1H), 6.77 (s, 1H), 5.74 (s, 1H), 2.12
(s, 3H), 1.88 (s, 3H), 1.13 (s, 9H); 13C NMR (101 MHz, CDCl3) δ
201.4, 170.2, 156.0, 135.5, 134.2, 132.5, 130.1, 129.9, 127.9,
120.7, 120.6, 119.4, 80.7, 26.5, 25.8, 20.7, 19.5; IR (neat) νmax
3414, 2962, 1749, 1732, 1602, 1429, 1259, 1107, 1016 cm-1; MS
(EI) m/z (%) 445 (Mþ - 1, 5) 432 (39), 431 (100), 347 (23), 323
(50), 203 (13). Anal. Calcd for C27H30O4Si: C, 72.61; H, 6.77.
Found: C, 72.45; H, 6.81.
1-(3-(tert-Butyldimethylsilyloxy)phenyl)-2-oxopropyl acetate
(2l): 257 mg, 80% yield; pale brown oil; Rf 0.47 (10:1 hexane/
EtOAc); 1H NMR (400 MHz, CDCl3) δ 7.32-7.22 (m, 1H), 7.00
(d, J = 8.0 Hz, 1H), 6.87 (br s, 2H), 5.91 (s, 1H), 2.19 (s, 3H),
2.10 (s, 3H), 0.98 (s, 9H), 0.20 (s, 6H); 13C NMR (101 MHz,
CDCl3) δ 201.5, 170.2, 156.2, 134.5, 130.1, 121.0, 120.9, 119.7,
80.7, 26.1, 25.6, 20.7, 18.2, -4.4; IR (neat) νmax 2955, 2932, 1745,
1732, 1602, 1446, 1371, 1238, 1051 cm-1; MS (EI) m/z (%) 321
(Mþ - 1, 17), 303 (8), 289 (52), 279 (11), 230 (16), 207 (100), 165
(6). Anal. Calcd for C17H26O4Si: C, 63.32; H, 8.13. Found: C,
63.51; H, 8.22.
1-(Naphthalen-1-yl)-2-oxopropyl acetate (2r): 230 mg, 95%
yield; pale yellow thick oil; Rf 0.34 (10:1 hexane/EtOAc); H
1
NMR (400 MHz, CDCl3) δ 8.13 (d, J = 8.0 Hz, 1H), 7.91 (br t,
J = 8.0 Hz, 2H), 7.59 (t, J = 8.0 Hz, 2H), 7.51 (dd, J = 8.0, 16
Hz, 2H), 6.68 (s, 1H), 2.22 (s, 3H), 2.07 (s, 3H); 13C NMR (101
MHz, CDCl3) δ 201.8, 170.2, 134.1, 131.2, 130.3, 129.4, 128.9,
128.3, 127.2, 126.3, 125.3, 123.8, 79.4, 26.3, 20.8; IR (neat) νmax
3053, 2926, 1743, 1730, 1512, 1427, 1371, 1229, 1045 cm-1; MS
(EI) m/z (%) 243 (Mþ þ 1, 100), 217 (6), 185 (31). Anal. Calcd
for C15H14O3: C, 74.36; H, 5.82. Found: C, 74.46; H, 5.78.
2-Oxo-1-o-tolylpropyl acetate (2s): 189 mg, 92% yield; color-
less oil; Rf 0.33 (10:1 hexane/EtOAc); 1H NMR (400 MHz,
CDCl3) δ 7.31-7.21 (m, 4H), 6.25 (s, 1H), 2.45 (s, 3H), 2.18 (s,
3H), 2.09 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 201.7, 170.3,
137.2, 131.8, 131.3, 129.4, 128.7, 126.7, 78.3, 26.3, 20.8, 19.5; IR
(neat) νmax 2930, 1747, 1732, 1566, 1429, 1373, 1234, 1045 cm-1
;
MS (EI) m/z (%) 205 (Mþ - 1, 100), 161 (76), 135 (36). Anal.
Calcd for C12H14O3: C, 69.88; H, 6.84. Found: C, 69.95; H, 6.78.
1-(2-(Allyloxy)phenyl)-2-oxopropyl acetate (2t): 238 mg, 96%
yield; colorless oil; Rf 0.34 (10:1 hexane/EtOAc); 1H NMR (400
MHz, CDCl3) δ 7.38-7.29 (m, 2H), 6.99 (t, J = 8.0 Hz, 1H),
6.94 (d, J = 8.0 Hz, 1H), 6.51 (s, 1H), 6.12-5.98 (m, 1H), 5.43
(d, J = 16 Hz, 1H), 5.31 (d, J = 8.0 Hz, 1H), 4.66-4.53 (m, 2H),
2.17 (s, 3H), 2.12 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 201.9,
170.3, 155.8, 132.6, 130.5, 129.4, 122.2, 121.2, 117.8, 112.3, 74.9,
69.1, 26.3, 20.7; IR (neat) νmax 3447, 3080, 2928, 1728, 1732,
1601, 1493, 1454, 1371, 1230, 1047 cm-1; MS (EI) m/z (%) 247
(Mþ - 1, 100), 207 (52), 187 (31), 163 (65), 121 (13). Anal. Calcd
for C14H16O4: C, 67.73; H, 6.50. Found: C, 67.85; H, 6.44.
1-(Anthracen-9-yl)-2-oxopropyl acetate (2u): 248 mg, 85%
yield; pale brown solid; mp 113-114 °C; Rf 0.38 (6:1 hexane/
EtOAc); 1H NMR (400 MHz, CDCl3) δ 8.58 (s, 1H), 8.39 (br d,
J = 7.6 Hz, 2H), 8.07 (d, J = 8.4 Hz, 2H), 7.66 (s, 1H), 7.61 (t,
J = 8.0 Hz, 2H), 7.53 (t, J = 8.0 Hz, 2H), 2.24 (s, 3H), 1.88 (s, 3H);
13C NMR (101 MHz, CDCl3) δ 202.2, 170.3, 131.6, 130.9, 130.3,
129.4, 127.4, 125.3, 124.4, 124.0, 75.6, 26.3, 20.8; IR (KBr) νmax
2935, 1738, 1722, 1523, 1371, 1240, 1074 cm-1; MS (EI) m/z (%)
292 (Mþ, 16), 291 (Mþ - 1, 49), 279 (20), 263 (73), 249 (24), 223
(45), 208 (100). Anal. Calcd for C19H16O3: C, 78.06; H, 5.52.
Found: C, 78.12; H, 5.47.
1-(Benzo[d][1,3]dioxol-5-yl)-2-oxopropyl acetate (2m): 214 mg,
91% yield; pale yellow thick oil; Rf 0.35 (6:1 hexane/EtOAc);
1H NMR (400 MHz, CDCl3) δ 6.89 (d, J = 8.0 Hz, 1H),
6.85-6.81 (m, 2H), 5.99 (s, 2H), 5.88 (s, 1H), 2.18 (s, 3H), 2.11
(s, 3H); 13C NMR (101 MHz, CDCl3) δ 201.6, 170.3, 148.6,
148.2, 126.6, 122.4, 108.7, 108.2, 101.4, 80.5, 26.1, 20.7; IR (neat)
ν
max 2961, 2885, 1732, 1711, 1442, 1369, 1232, 1101, 1033 cm-1
;
MS (EI) m/z (%) 237 (Mþ þ 1, 100), 229 (10), 217 (5), 151 (8).
Anal. Calcd for C12H12O5: C, 61.01; H, 5.12. Found: C, 61.25;
H, 5.08.
1-(2-Chlorophenyl)-2-oxopropyl acetate (2n): 211 mg, 93%
yield; pale yellow oil; Rf 0.44 (10:1 hexane/EtOAc); H NMR
1
(400 MHz, CDCl3) δ 7.46 (d, J = 7.6 Hz, 1H), 7.38 (d, J = 7.2
Hz, 1H), 7.36-7.28 (m, 2H), 6.52 (s, 1H), 2.18 (s, 3H), 2.16
(s, 3H); 13C NMR (101 MHz, CDCl3) δ 200.8, 169.9, 133.9,
131.5, 130.6. 130.1, 129.7, 127.5, 76.9, 26.6, 20.6; IR (neat) νmax
2930, 1749, 1738, 1442, 1371, 1230, 1043 cm-1; MS (EI) m/z (%)
229 (Mþ þ 2, 27), 228 (Mþ þ 1, 10), 227 (Mþ, 100), 191 (16), 151
(13), 135 (8), 91 (8). Anal. Calcd for C11H11ClO3: C, 58.29; H,
4.89. Found: C, 58.41; H, 4.82.
1-(2-Bromophenyl)-2-oxopropyl acetate (2o): 236 mg, 87%
yield; colorless oil; Rf 0.47 (10:1 hexane/EtOAc); 1H NMR
(400 MHz, CDCl3) δ 7.64 (d, J = 8.0 Hz, 1H), 7.39-7.31 (m,
2H), 7.29-7.22 (m, 1H), 6.51 (s, 1H), 2.18 (s, 3H), 2.16 (s, 3H);
13C NMR (101 MHz, CDCl3) δ 200.8, 169.9, 133.3, 133.1, 130.8,
1-(2,6-Dichlorophenyl)-2-oxopropyl acetate (2v): 237 mg, 91%
yield; colorless thick oil; Rf 0.41 (8:1 hexane/EtOAc); H NMR
1
(400 MHz, CDCl3) δ 7.37 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.0 Hz,
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Ghosh et al.
JOCArticle
1H), 6.88 (s, 1H), 2.20 (s, 3H), 2.18 (s, 3H); 13C NMR (101 MHz,
1H), 3.83-3.66 (m, 2H), 3.48-3.33 (m, 2H), 2.12 (s, 3H), 2.11 (s,
3H), 1.92-1.84 (m, 1H), 1.84-1.72 (m, 2H), 1.72-1.58 (m, 3H),
1.58-1.42 (m, 4H); 13C NMR (101 MHz, CDCl3) δ 205.1, 170.5,
98.9, 78.4, 66.6, 62.4, 30.6, 27.2, 26.0, 25.4, 20.6, 19.6; IR (neat)
CDCl3) δ 200.7, 169.6, 136.6, 131.5, 130.9, 129.0, 76.2, 26.3, 20.6;
IR (neat) νmax 2930, 1768, 1730, 1562, 1435, 1373, 1229, 1047 cm-1
;
MS (EI) m/z (%) 263 (Mþ þ 2, 24), 261 (Mþ, 25), 241 (32), 233
(67), 201 (45), 183 (100), 169 (40), 135 (32). Anal. Calcd for
C11H10Cl2O3: C, 50.60; H, 3.86. Found: C, 50.71; H, 3.90.
1-(2,6-Dimethoxyphenyl)-2-oxopropyl acetate (2w): 235 mg,
93% yield; colorless solid; mp 122-123 °C; Rf 0.32 (10:1 hexane/
EtOAc); 1H NMR (400 MHz, CDCl3) δ 7.32 (br t, J = 8.0 Hz,
1H), 6.67 (s, 1H), 6.58 (d, J = 8.0 Hz, 2H), 3.80 (s, 6H), 2.15 (s,
3H), 2.04 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 202.6, 170.4,
158.9, 131.3, 111.7, 104.1, 71.6, 55.9, 25.4, 20.9; IR (KBr) νmax
2943, 1747, 1728, 1595, 1479, 1369, 1190, 1111, 1039 cm-1; MS
(EI) m/z (%) 275 (Mþ þ Na, 38), 253 (Mþ þ 1, 6), 247 (10), 223
(4), 193 (100), 181 (2), 165 (60). Anal. Calcd for C13H16O5: C,
61.90; H, 6.39. Found: C, 61.85; H, 6.43.
ν
max 2941, 1741, 1726, 1491, 1372, 1253, 1097 cm-1; MS (EI) m/z
(%) 242 (Mþ þ 1, 16), 241 (Mþ, 100), 140 (10), 108 (8). Anal.
Calcd for C13H22O5: C, 60.45; H, 8.58. Found: C, 60.32; H, 8.49.
3,5-Dimethyl-2-oxohexan-3-yl acetate (2ad): 174 mg, 94%
yield; colorless oil; Rf 0.60 (19:1 hexane/EtOAc); 1H NMR
(400 MHz, CDCl3) δ 2.11 (s, 3H), 2.07 (s, 3H), 1.81-1.59 (m,
3H), 1.50 (s, 3H), 0.93 (s, 6H); 13C NMR (101 MHz, CDCl3) δ
206.2, 169.7, 86.2, 44.1, 24.2, 23.6, 23.4, 23.5, 20.8, 20.1; IR
(neat) νmax 2959, 1738, 1718, 1469, 1371, 1253, 1130 cm-1; MS
(EI) m/z (%) 187 (100), 159 (32), 127 (78), 109 (13). Anal. Calcd
for C10H18O3: C, 64.49; H, 9.74. Found: C, 64.55; H, 9.69.
3-Oxo-2-phenylbutan-2-yl acetate (2ae): 156 mg, 76% yield;
1
2-Oxo-1-(thiophen-2-yl)propyl acetate (2x): 149 mg, 75%
yield; thick pale brown oil; Rf 0.30 (6:1 hexane/EtOAc); 1H
NMR (400 MHz, CDCl3) δ 7.40 (br d, J = 4.8 Hz, 1H), 7.15 (s,
pale yellow oil; Rf 0.41 (10:1 hexane/EtOAc); H NMR (400
MHz, CDCl3) δ 7.46 (d, J = 8.0 Hz, 2H), 7.38 (t, J = 8.0 Hz,
2H), 7.33 (d, J = 8.0 Hz, 1H), 2.26 (s, 3H), 1.95 (s, 3H), 1.85 (s,
3H); 13C NMR (101 MHz, CDCl3) δ 203.6, 169.9, 138.5, 128.7,
128.1, 124.7, 87.4, 23.5, 22.8, 21.3; IR (neat) νmax 3007, 2941,
1739, 1724, 1494, 1448, 1255, 1105, 1018 cm-1; MS (EI) m/z (%)
205 (Mþ - 1, 100), 181 (5), 108 (10). Anal. Calcd for C12H14O3:
C, 69.88; H, 6.84. Found: C, 69.95; H, 6.81.
2-(4-Chlorophenyl)-3-oxobutan-2-yl acetate (2af): 197 mg,
82% yield; pale yellow oil; Rf 0.39 (6:1 hexane/EtOAc); 1H
NMR (400 MHz, CDCl3) δ 7.36 (q, J = 8.8 Hz, 4H), 2.25 (s,
3H), 1.94 (s, 3H), 1.82 (s, 3H); 13C NMR (101 MHz, CDCl3) δ
203.3, 169.9, 137.1, 134.2, 128.9, 126.3, 87.1, 23.6, 22.9, 21.3; IR
(neat) νmax 2941, 1741, 1726, 1491, 1372, 1253, 1097 cm-1; MS (EI)
m/z (%) 242 (Mþ þ 1, 16), 241 (Mþ, 100), 140 (10), 108 (8). Anal.
Calcd for C12H13ClO3: C, 59.88; H, 5.44. Found: C, 59.76; H, 5.41.
1-Acetylcyclopentyl acetate (2ag): 163 mg, 96% yield; color-
less oil; Rf 0.45 (10:1 hexane/EtOAc); 1H NMR (400 MHz,
CDCl3) δ 2.22-2.13 (m, 2H), 2.12 (s, 3H), 2.10 (s, 3H),
1.93-1.83 (m, 2H), 1.82-1.59 (m, 4H); 13C NMR (101 MHz,
CDCl3) δ 205.7, 170.8, 93.8, 35.5, 24.8, 24.3, 21.0; IR (neat) νmax
2962, 1738, 1716, 1435, 1371, 1257, 1176, 1020 cm-1; MS (EI)
m/z (%) 185 (Mþ þ 14, 100), 171 (Mþ þ 1, 93), 167 (16), 153 (52),
135 (40), 111 (20), 91 (6). Anal. Calcd for C9H14O3: C, 63.51; H,
8.29. Found: C, 63.45; H, 8.32.
1H), 7.05 (br d, J = 3.6 Hz, 1H), 6.24 (s, 1H), 2.19 (s, 6H); 13
C
NMR (101 MHz, CDCl3) δ 200.5, 170.1, 134.5, 128.4, 127.7,
127.3, 75.8, 26.0, 20.6; IR (neat) νmax 3277, 3109, 2930, 1747,
1732, 1435, 1373, 1232, 1039 cm-1; MS (EI) m/z (%) 198 (Mþ,
10), 197 (Mþ - 1, 100), 185 (5), 155 (10), 153 (8). Anal. Calcd for
C9H10O3S: C, 54.53; H, 5.08. Found: C, 54.68; H, 5.15.
1-(1-Benzoyl-1H-indol-3-yl)-2-oxopropyl acetate (2y): 261 mg,
78% yield; thick yellow oil; Rf 0.37 (5:1 hexane/EtOAc); 1H
NMR (400 MHz, CDCl3) δ 8.37 (d, J = 8.0 Hz, 1H), 7.74 (d,
J = 7.2 Hz, 2H), 7.66 (t, J = 8.4 Hz, 2H), 7.56 (t, J = 7.6 Hz,
2H), 7.46 (s, 1H), 7.43 (d, J = 8.0 Hz, 1H), 7.37 (t, J = 7.2 Hz,
1H), 6.25 (s, 1H), 2.19 (s, 3H), 2.17 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 200.9, 170.3, 168.4, 136.5, 133.9, 132.4, 129.2, 128.9,
128.3, 127.6, 125.9, 124.5, 119.9, 116.6, 114.3, 74.1, 26.2, 20.7;
IR (neat) νmax 3449, 2926, 1743, 1730, 1695, 1454, 1359, 1222,
1053 cm-1; MS (EI) m/z (%) 335 (Mþ, 28), 334 (Mþ - 1, 100),
292 (8), 229 (5), 121 (5). Anal. Calcd for C20H17NO4: C, 71.63;
H, 5.11; N, 4.18. Found: C, 71.48; H, 5.25; N, 4.22.
2-Oxononan-3-yl acetate (2z): 188 mg, 94% yield; colorless
oil; Rf 0.39 (7:1 hexane/EtOAc); 1H NMR (400 MHz, CDCl3) δ
4.96 (dd, J = 4.0, 8.0 Hz, 1H), 2.14 (s, 6H), 1.77-1.70 (m, 2H),
1.40-1.25 (m, 8H), 0.87 (br t, J = 8.0 Hz, 3H); 13C NMR (101
MHz, CDCl3) δ 205.4, 170.6, 78.8, 31.5, 30.3, 28.9, 26.1, 25.1,
22.5, 20.7, 14.0; IR (neat) νmax 2926, 1745, 1728, 1564, 1429,
1373, 1238, 1043 cm-1; MS (EI) m/z (%) 201 (Mþ þ 1, 100), 183
(13), 181 (10), 141 (29), 123 (8). Anal. Calcd for C11H20O3: C,
65.97; H, 10.07. Found: C, 65.85; H, 10.15.
1-Acetylcyclohexyl acetate (2ah): 156 mg, 85% yield; colorless
oil; Rf 0.48 (10:1 hexane/EtOAc); 1H NMR (400 MHz, CDCl3) δ
2.11 (s, 3H), 2.07 (s, 3H), 2.02 (d, J = 12.0 Hz, 2H), 1.62 (bt, J =
12.0 Hz, 5H), 1.53 (q, J = 12 Hz, 2H), 1.25 (br q, J = 12.0 Hz,
1H); 13C NMR (101 MHz, CDCl3) δ 207.3, 170.2, 85.2, 30.7,
25.0, 23.6, 21.1, 21.0; IR (neat) νmax 2941, 1738, 1716, 1452,
1371, 1240, 1140, 1018 cm-1; MS (EI) m/z (%) 185 (Mþ þ 1, 68),
168 (4), 167 (47), 149 (4), 126 (8), 125 (100). Anal. Calcd for
C10H16O3: C, 65.19; H, 8.75. Found: C, 65.35; H, 8.71.
3-Oxo-1-phenylbutan-2-yl acetate (2aa): 175 mg, 85% yield;
colorless oil; Rf 0.36 (10:1 hexane/EtOAc); H NMR (400 MHz,
1
CDCl3) δ 7.31 (br q, J = 7.2 Hz, 2H), 7.25 (d, J = 6.0 Hz, 1H), 7.21
(d, J = 7.2 Hz, 2H), 5.21 (dd, J = 4.8, 8.0 Hz, 1H), 3.11 (dd, J =
4.8, 14.4 Hz, 1H), 3.01 (dd, J = 8.4, 14 Hz, 1H), 2.08 (s, 3H), 2.07 (s,
3H); 13C NMR (101 MHz, CDCl3) δ 205.3, 170.4, 135.9, 129.3,
128.6, 127.1, 79.1, 36.7, 26.9, 20.6; IR (neat) νmax 3460, 2928, 1745,
1730, 1496, 1433, 1373, 1238, 1070 cm-1; MS (EI) m/z (%) 207
(Mþ þ 1, 86), 187 (43), 179 (41), 161 (13), 147 (100), 129 (25). Anal.
Calcd for C12H14O3: C, 69.88; H, 6.84. Found: C, 69.75; H, 6.88.
8-Bromo-2-oxooctan-3-yl acetate (2ab): 228 mg, 86% yield;
colorless oil; Rf 0.62 (10:1 hexane/EtOAc); 1H NMR (400 MHz,
CDCl3) δ4.97 (q, J = 4.4 Hz, 1H), 3.93 (t, J = 6.4 Hz, 2H), 2.14 (s,
6H), 1.92-1.81 (m, 2H), 1.80-1.65 (m, 2H), 1.53-1.45 (m, 4H);
13C NMR (101 MHz, CDCl3) δ 205.3, 170.6, 78.5, 33.5, 32.4, 30.1,
27.7, 26.1, 24.3, 20.7; IR (neat) νmax 3456, 2947, 1743, 1730, 1433,
1373, 1240, 1047 cm-1; MS (EI) m/z (%) 267 (Mþ þ 2, 66), 265
(Mþ, 62), 245 (12), 199 (100), 167 (24), 107 (6). Anal. Calcd for
C10H17BrO3: C, 45.30; H, 6.46. Found: C, 45.21; H, 6.52.
1-Acetylcycloheptyl acetate (2ai): 180 mg, 91% yield; colorless
oil; Rf 0.42 (7:1 hexane/EtOAc); 1H NMR (400 MHz, CDCl3) δ
2.10 (s, 3H), 2.07 (s, 3H), 2.03-1.87 (m, 4H), 1.56 (br s, 8H); 13
C
NMR (101 MHz, CDCl3) δ 207.1, 170.4, 89.2, 34.4, 29.4, 23.6,
22.8, 21.1; IR (neat) νmax 2930, 1736, 1720, 1458, 1371, 1251,
1147, 1024 cm-1; MS (EI) m/z (%) 197 (Mþ - 1, 100), 185 (60),
181 (95), 141 (50), 125 (86), 93 (27). Anal. Calcd for C11H18O3:
C, 66.64; H, 9.15. Found: C, 66.71; H, 9.22.
8-Acetyl-1,4-dioxaspiro[4.5]decan-8-yl acetate (2aj): 194 mg,
80% yield; pale yellow oil; Rf 0.51 (6:1 hexane/EtOAc); 1H
NMR (400 MHz, CDCl3) δ 4.01-3.91 (m, 4H), 2.16 (s, 6H),
2.15-2.10 (m, 2H), 2.12-1.97 (m, 2H), 1.86-1.75 (m, 2H),
1.73-1.63 (m, 2H); 13C NMR (101 MHz, CDCl3) δ 206.4, 170.3,
107.5, 83.9, 64.4, 64.3, 30.0, 28.8, 24.0, 21.0 ; IR (neat) νmax 2959,
1732, 1714, 1444, 1371, 1230, 1107,1025 cm-1; MS (EI) m/z (%)
243 (Mþ þ 1, 38), 225 (20), 205 (2), 184 (22), 183 (100), 139 (6), 87
(16). Anal. Calcd for C12H18O5: C, 59.49; H, 7.49. Found: C,
59.71; H, 7.38.
2-Oxo-6-(tetrahydro-2H-pyran-2-yloxy)hexan-3-yl acetate
(2ac): 201 mg, 78% yield; colorless oil; Rf 0.47 (10:1 hexane/
EtOAc); 1H NMR (400 MHz, CDCl3) δ 4.99 (br s, 1H), 4.52 (s,
510 J. Org. Chem. Vol. 76, No. 2, 2011

Ghosh et al.
JOCArticle
Preparation of tert-butyl-3-(2-hydroxy-4-(trimethylsilyl)but-
3-ynyl)-1H-indole-1-carboxylate (15): 1.46 g, 89% yield; thick
yellow oil; Rf 0.4 (12:1 hexane/EtOAc); H NMR (400 MHz,
EtOAc); 1H NMR (400 MHz, CDCl3) δ 8.10 (br s, 1H), 7.64 (d,
J = 8.0 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.27 (s, 1H), 7.22 (t, J =
7.2 Hz, 1H), 7.15 (t, J = 7.2 Hz, 1H), 4.53 (d, J= 4.8 Hz, 1H), 3.47
(d, J = 4.0 Hz, 1H), 3.32 (dd, J = 4.4, 14.8 Hz, 1H), 3.14 (dd, J =
6.6, 15.2 Hz, 1H), 2.21 (s, 3H); 13C NMR (101 MHz, CDCl3) δ
209.8, 136.1, 127.5, 122.9, 122.2, 119.6, 118.7, 111.2, 110.4, 77.1,
29.6, 25.9; IR (neat) νmax 3546, 2959, 1732, 1444, 1371, 1230,
1107,1025 cm-1; MS (EI) m/z (%) 205 (Mþ þ 2, 38), 204 (Mþ þ 1,
100). Anal. Calcd for C12H13NO2: C, 70.92; H, 6.45; N, 6.89.
Found: C, 70.85; H, 6.39; N, 6.81.
1
CDCl3) δ 8.15 (br s, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.54 (s, 1H),
7.35-7.31 (m, 1H), 7.27-7.23 (m, 1H), 4.67 (d, J = 4.0 Hz, 1H),
3.13 (t, J = 4.0 Hz, 2H), 2.10 (s, 1H), 1.67 (s, 9H), 0.15 (s, 9H);
13C NMR (101 MHz, CDCl3) δ 149.6, 135.5, 130.7, 124.6, 124.4,
122.5, 119.3, 115.3, 115.2, 106.1, 90.2, 83.6, 62.5, 33.5, 28.2,
-0.2; IR (neat) νmax 2964, 2181, 1745, 1608, 1456, 1099 cm-1
;
MS (EI) m/z (%) 358 (Mþ þ 1, 100), 314 (13), 279 (13), 163 (11),
135 (11). Anal. Calcd for C20H27NO3Si: C, 67.19; H, 7.61; N,
3.92. Found: C, 67.25; H, 7.58; N, 3.88.
O18-Labeled 1-acetylcyclohexyl acetate (27): 152 mg, 82%
yield; colorless oil; Rf 0.44 (10:1 hexane/EtOAc); 1H NMR (400
MHz, CDCl3) δ 2.11 (s, 3H), 2.07 (s, 3H), 2.02 (d, J = 12 Hz,
2H), 1.62 (br t, J = 12 Hz, 5H), 1.53 (q, J = 12 Hz, 2H), 1.25
(br q, J = 12 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 207.3,
170.2, 85.2, 30.7, 25.0, 23.6, 21.1, 21.0; MS (EI) m/z (%) 187
(Mþ þ 1, 100), 169 (27), 157 (13), 125 (30).
tert-Butyl-3-(2-acetoxybut-3-ynyl)-1H-indole-1-carboxylate
(16): 532 mg, 83% yield; thick yellow oil; Rf 0.30 (19:1 hexane/
EtOAc); 1H NMR (400 MHz, CDCl3) δ 8.21-8.11 (br s, 1H), 7.61
(d, J = 8.0 Hz, 1H), 7.54 (s, 1H), 7.32 (t, J = 8.0 Hz, 1H), 7.26 (d,
J = 7.2 Hz, 1H), 5.64 (q, J = 6.8 Hz, 1H), 3.21 (q, J = 2.0 Hz, 2H),
2.48(s, 1H),2.07(s, 3H), 1.68(s, 9H);13C NMR (101 MHz, CDCl3)
δ 169.8, 149.7, 135.3, 130.5, 124.4, 122.5, 119.1, 115.3, 114.8, 83.7,
80.9, 74.3, 63.5, 30.6, 28.2, 21.0; IR (neat) νmax 2978, 1730, 1612,
1452, 1371, 1226, 1151, 1022 cm-1; MS (EI) m/z (%) 328 (Mþ þ 1,
100), 296 (43), 183 (14), 100 (8). Anal. Calcd for C19H21NO4: C,
69.71; H, 6.47; N, 4.28. Found: C, 69.75; H, 6.41; N, 4.34.
1-(1-Hydroxycyclohexyl)ethanone (28): 47 mg, 78%, colorless
oil; Rf 0.33 (8:1 hexane/EtOAc); 1H NMR (400 MHz, CDCl3) δ
3.57 (s, 1H), 2.24 (s, 3H), 1.81-1.59 (m, 6H), 1.48 (d, J = 4.8 Hz,
2H), 1.24 (br s, 2H); 13C NMR (101 MHz, CDCl3) δ 212.8, 78.0,
33.8, 29.7, 25.3, 23.7, 21.1; IR (neat) νmax 3260, 1730, 1425, 1367,
1234, 1026 cm-1; MS (EI) m/z (%) 143 (Mþ þ 1, 58), 129 (55),
125 (62), 99 (9), 81(11). Anal. Calcd for C8H14O2: C, 67.57; H,
9.92. Found: C, 67.45; H, 9.86.
tert-Butyl 3-(2-hydroxy-3-oxobutyl)-1H-indole-1-carboxylate
(17): 350 mg, 83% yield; thick yellow oil; Rf 0.32 (10:1 hexane/
1
EtOAc); H NMR (400 MHz, CDCl3) δ 8.22-8.13 (br s, 1H),
7.57 (d, J = 8.0 Hz, 1H), 7.46 (s, 1H), 7.33 (t, J = 8.4 Hz, 1H),
7.27 (d, J = 6.0 Hz, 1H), 5.28 (q, J = 5.2 Hz, 1H), 3.21 (dd, J =
4.8, 15.2 Hz, 1H), 3.13 (dd, J = 7.6, 15.2 Hz, 1H), 2.14 (s, 3H),
2.10 (s, 3H), 1.68 (s, 9H); 13C NMR (101 MHz, CDCl3) δ 205.3,
170.4, 149.6, 135.3, 130.3, 124.6, 124.3, 122.6, 118.9, 115.3,
114.9, 83.8, 78.2, 28.2, 26.9, 26.2, 20.7; IR (neat) νmax 2980,
1743,1732, 1606, 1454, 1371, 1255, 1157,1089 cm-1; MS (EI) m/z
(%) 344 (Mþ - 1, 15), 304 (34), 277 (25), 244 (100), 200 (12), 184
(64). Anal. Calcd for C19H23NO5: C, 66.07; H, 6.71; N, 4.06.
Found: C, 65.88; H, 6.78; N, 4.12.
Acknowledgment. We gratefully acknowledge the Univer-
sity of Hyderabad, ACRHEM, and the DST (Grant No. SR/
S1/OC-34/2009) for support. N.G. and S.N. thank CSIR,
India for a graduate fellowship. We are grateful to Mr. T.
Chatterjee for solving the X-ray crystallographic data for the
product 2w. We sincerely thank Professor T. P. Radhakrishnan
for proofreading the manuscript.
Supporting Information Available: Detailed experimental
procedures, spectra, and X-ray data. This material is available
free of charge via the Internet at http://pubs.acs.org.
3-Hydroxy-4-(1H-indol-3-yl)butan-2-one (actinopolymorphol
B; 18): 115 mg, 56% yield; thick yellow oil; Rf 0.18 (5:1 hexane/
J. Org. Chem. Vol. 76, No. 2, 2011 511