Synthesis of α-acyloxyketone derivatives via the platinum-catalyzed migration of propargylic esters

Article abstract of DOI:10.1248/cpb.c15-00417

The synthesis of α-acyloxyketones via the migration of a propargylic ester followed by the intramolecular nucleophilic addition of the resulting allene was achieved using a cationic platinum catalyst. The optimized conditions for this transformation were

Full text of DOI:10.1248/cpb.c15-00417

710
Chem. Pharm. Bull. 63, 710–719 (2015)
Vol. 63, No. 9
Regular Article
Synthesis of α-Acyloxyketone Derivatives via the Platinum-Catalyzed
Migration of Propargylic Esters
Chihiro Tsukano, Sho Yamamoto, and Yoshiji Takemoto*
Graduate School of Pharmaceutical Sciences, Kyoto University; Yoshida, Sakyo-ku, Kyoto 606–8501, Japan.
Received May 15, 2015; accepted June 8, 2015
The synthesis of α-acyloxyketones via the migration of a propargylic ester followed by the intramolecular
nucleophilic addition of the resulting allene was achieved using a cationic platinum catalyst. The optimized
conditions for this transformation were determined to be 3mol% of Pt(cod)Cl2, 3mol% of AgNTf2, and 3eq
of water in toluene at 100°C, and these conditions were successfully applied to the synthesis of a wide variety
of α-aryl-α-acyloxyketones. The mechanism of this reaction was evaluated in detail based on the results of
isotope labeling experiments using H218O.
Key words platinum; propargylic ester migration; α-acyloxyketone
α-Acyloxyketone, which is a protected form of α-hydroxyketone, propargyl acetate 1 with PdCl2(MeCN)2 gave a 1:1 mixture
is a fundamental structure that can be found in a broad range of α-acyloxyketone 2 and α,β-unsaturated ketone 3 via the
of natural products and bioactive compounds, including hain- rearrangement of the acetyl group (Chart 2(a)). Ohfune et al.24)
anmurpanin,1) paniculatin2) and murpaniculol senecioate3) (Fig. also reported the synthesis of α-acyloxy-α′-siloxyketone 4
1). α-Acyloxyketone has also been used as a simple starting using a gold catalyst (Chart 2(b)). Under Ohfune’s conditions,
material for the stereoselective synthesis of a variety of differ- it was observed that substrates without a silyl group did not
ent structures, including numerous 1,2-diols4–8) and heterocy- undergo the reaction, and it was therefore assumed that the
clic systems.9–11) Based on the importance of α-acyloxyketones silyl group was essential for stabilizing the β cation of reac-
to chemistry, the development of a concise synthetic method tion intermediate 5 (or 6). Although these reactions provided
for the preparation of α-acyloxyketone derivatives is im- facile access to the α-acyloxyketones 2 and 4 from the readily
portant. Although a wide variety of synthetic methods have accessible propargyl esters 1 and 3, several opportunities still
been investigated to date,12,13) reports pertaining to the direct remained to improve on this reaction in terms of the selectiv-
synthesis of α-acyloxyketone III by the oxidation of alkyne I ity and substrate scope.
are rare, most likely because of the difficulties associated with
For improving the scope of this reaction, we focused on
suppressing the over-oxidation of the product and controlling enhancing the π-acidity of the transition metal catalyst (i.e.,
the regioselectivity of the reaction14–16) (Chart 1). To allow palladium, gold or platinum catalyst) by decreasing its elec-
for the direct synthesis of α-acyloxyketone III from alkyne I, tron density.17–20) If allene 9, which was derived from 7, could
several researchers directed their attention towards the transi- be strongly activated by a π-acidic transition metal catalyst,
tion metal-catalyzed migration of propargylic esters17–20) to then the addition of the internal ester or a water molecule to
affect a facile oxidative transformation.21–30) For example, in the allene would give α-acyloxyketone 8 without the require-
1991, Schick and Mahrwald21) reported that the treatment of ment for a neighboring group to stabilize the transition state
(Chart 3). Given that propargyl ester 7 can be readily prepared
by the Sonogashira coupling of an alkyne bearing a propargyl
ester to an aryl halide or the nucleophilic addition of a suitable
acetylide to an aldehyde followed by acylation, this transfor-
mation could be used as a concise method for a preparation
of α-acyloxyketones. In this paper, we describe our recent ef-
forts towards the synthesis of α-acyloxyketones based on the
platinum-catalyzed migration of propargylic esters.
Results and Discussion
Pivaloyl ester 11a was selected as a model substrate to
investigate the synthesis of α-acyloxyketone 12a because it
would avoid the undesired hydrolysis of the ester (Table 1).
Several gold and platinum catalysts were initially screened
against the model substrate in toluene at 60°C (Table 1, en-
tries 1–7). Cationic gold catalysts derived from the reaction of
AuCl or AuCl3 with AgNTf2 did not give the desired product
12a (Table 1, entries 1, 2). To reduce the cationic property
of the catalyst, we investigated the use of Au(PPh3)Cl and
Pt(PPh3)2Cl2 with AgNTf2. However, these two systems also
Fig. 1. Selected Natural Products Containing an α-Acyloxyketone
Moiety
Chart 1. Concept for the Synthesis of α-Acyloxyketones by the Oxida-
tion of an Alkyne
*To whom correspondence should be addressed. e-mail: takemoto@pharm.kyoto-u.ac.jp
© 2015 The Pharmaceutical Society of Japan

Vol. 63, No. 9 (2015)
Chem. Pharm. Bull.
711
Chart 2. Synthesis of α-Acyloxyketones from Propargyl Esters Using a Metal Catalyst
Chart 3. Synthetic Strategy for α-Acyloxyketone
failed to provide any of the desired product 12a, presumably hydrolysis of the reaction intermediate, and we subsequently
because the phosphine ligand was strongly coordinated to the investigated the addition of three equivalents of water to the
metal for decreasing its cationic character (Table 1, entries 3, reaction mixture. As anticipated, the yield of the reaction was
4). Based on this result, we proceeded to investigate the use improved to 63% following the addition of 3eq, with the reac-
of a CO atmosphere and cyclooctadiene, which have been tion reaching completion within 2h (Table 1, entry 13). The
reported to weakly coordinate to metals.31–35) While the reac- impact of raising the reaction temperature to 100°C was also
tion using 10mol% of PtCl2 under an atmosphere of CO gave investigated and led to a decrease in the reaction time (Table
the desired product 12a in 14% yield, the use of 10mol% of 1, entry 14). Based on these results, the optimized conditions
Pt(cod)Cl2/AgNTf2 provided 12a in a much greater yield of were set as follows: 3mol% of Pt(cod)Cl2, 3mol% of AgNTf2
75% within 1h (Table 1, entries 5, 6).36) Interestingly, reac- and 3eq of water in toluene at 100°C. To the best of our
tions using only Pt(cod)Cl2 or AgNTf2 did not provide any knowledge, this work represents the first reported example
of the desired product (Table 1, entries 7, 8). Taken together, of the migration of a propargylic ester catalyzed by a mono-
these results indicated that the use of a cationic platinum cata- cationic Pt catalyst, which was generated in situ from neutral
lyst with a weakly coordinating ligand would be important for Pt(cod)Cl2 and AgNTf2.
the success of this reaction. Further screening experiments
With the optimized conditions in hand, we proceeded to
confirmed that the previously reported conditions21,24) were not investigate the scope of the reaction using a variety of differ-
effective for this transformation (Table 1, entries 9–11). We ent substrates (Table 2). Substrates 11b–g bearing an electron-
then proceeded to investigate the possibility of reducing the withdrawing group at the para-position of the phenyl ring
amount of catalyst added to the reaction using the Pt(cod)Cl2/ (i.e., halogen, ester, nitrile, nitro or trifluoromethyl group)
AgNTf2 catalytic system (Table 1, entry 6).37) A reduction gave the corresponding α-alkoxyketones 12b–g in 69–89%
in the amount of catalyst to 3mol% led to a decrease in the yields (Table 2, entries 1–6). In contrast, substrates bearing an
yield to 44%, despite the reaction time being extended to 12h electron-donating group at the para position, such as a methyl
(Table 1, entry 12). Consideration of the reaction mechanism or methoxy group, gave much lower yields of the correspond-
(vide infra) revealed that water would be required for the ing α-alkoxyketone products, with the para-methoxy substrate

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Chem. Pharm. Bull.
Vol. 63, No. 9 (2015)
Table 1. Investigation of the Reaction Conditionsa)
Entry
Catalyst
Solvent
x
y
Time
Yieldb)
1
2
AuCl/AgNTf2
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
THF
10
10
10
10
10
10
10
10
20
10
10
3
None
None
None
None
None
None
None
None
None
None
1.0
24h
24h
24h
24h
24h
1h
N.D.c)
N.D.c)
N.D.c)
N.R.
AuCl3/AgNTf2
3
Au(PPh3)Cl/AgNTf2
Pt(PPh3)2Cl2/AgNTf2
PtCl2/CO
4
5
14%d)
6
Pt(cod)Cl2/AgNTf2
Pt(cod)Cl2
75%
7
24h
24h
18h
24h
6h
N.R.
8
AgNTf2
N.R.
9
PdCl2(MeCN)2
Trace
N.D.
Trace
44%
10
11
12
13
14e)
PdCl2(MeCN)2/AgNTf
Au(PPh3)Cl/AgSbF6
Pt(cod)Cl2/AgNTf2
Pt(cod)Cl2/AgNTf2
Pt(cod)Cl2/AgNTf2
Toluene
1,4-Dioxane
Toluene
Toluene
Toluene
None
3.0
12h
2h
3
63%
3
3.0
30min
67%
a) Reactions were carried out using 11a (0.3mmol), platinum catalyst (x mol%) and silver additive (x mol%) in solvent (6mL) with or without H2O (3.0eq) at 60°C.
b) Isolated yield. c) Complex mixture containing starting material 11a. d) NMR yield. e) The reaction was conducted at 100°C.
Table 2. Substrate Scopea)
Entry
Substrate
R1
R2
R3
R4
Product
Yieldb)
1
2
11b
11c
11d
11e
11f
Cl
Br
H
H
H
H
Piv
Piv
12b
12c
12d
12e
12f
77%
69%
82%
81%
84%
89%
47%
Trace
58%
84%
0%e)
0%e)
35%
48%
32%
14%
64%
3
CO2Me
CN
NO2
CF3
Me
OMe
H
H
H
Piv
4
H
H
Piv
5
H
H
Piv
6
11g
11h
11i
H
H
Piv
12g
12h
12i
7
8c)
H
H
Piv
H
H
Piv
9
11j
OMe
NO2
H
H
Piv
12j
10
11d)
12d)
13f)
14g)
15g)
16h)
17
11k
11l
H
H
Piv
12k
12l
H
OMe
NO2
H
Piv
11m
11n
11o
11p
11q
11r
H
H
Piv
12m
12n
12o
12p
12q
12r
H
H
Ac
H
H
H
Isobutyryl
Bz
H
H
H
H
H
H
(p-MeO)Bz
(p-NO2)Bz
H
H
H
a) Reactions were carried out using 11 (1.0eq), Pt(cod)Cl2 (3mol%), AgNTf2 (3mol%), H2O (3.0eq) and toluene at 100°C. b) Isolated yield. c) The reaction was performed
for 7h. d) No reaction. e) The reaction was performed for 24h. f) The reaction was performed for 10h. g) The reaction was performed for 2h. h) The reaction was performed
for 32h.
providing only a trace amount of the product (Table 2, entries ring failed to provide any of the desired products (Table 2, en-
7, 8). Substrates bearing a methoxy or nitro group at the tries 11, 12). The failure of these substrates can be rationalized
meta-position reacted smoothly to afford the desired products by the chelation of the functional groups to the cationic plati-
12j and 12k, with the electron-withdrawing group providing num catalyst, which would result in a decrease in the ability
a better yield (84%) than the electron-donating group (58%) of the catalyst to activate the alkyne, as shown in Fig. 2. Sev-
(Table 2, entries 9, 10). In sharp contrast, substrates 11l and eral acyl groups were examined instead of the pivaloyl group,
11m bearing a substituent at the ortho-position of their phenyl and the results revealed that the use of a smaller ester such

Vol. 63, No. 9 (2015)
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713
as acetyl or isobutyryl group resulted in lower yields of 35 H2O (path b). In this case, H2O would directly attack the
and 48%, respectively (Table 2, entries 13, 14). To determine central carbon of the allene intermediate to give intermedi-
the effect of the electronic state of the ester of the outcome ate I, which would be converted to α-acyloxyketone H via
of the reaction, we also investigated several non- and mono- sequential protodemetallation and tautomerization reactions.
substituted benzoyl groups. The results of these reactions It is noteworthy, however, that this route makes it difficult to
revealed that the use of an aromatic ring bearing an electron- explain the differences observed in the reactions of substrates
withdrawing group gave a better yield than an aromatic ring 11r and 11q.
bearing an electron-donating group or no substituent at all
(Table 2, entries 15–17).
Several isotope experiments were performed using H218O
to develop deeper insights into the reaction mechanism. For
A plausible mechanism for this reaction was proposed based path (a), it was envisaged that the carbonyl oxygen of the
on the results provided above (Chart 4). The initially coordi- ester would be labeled with 18O. In contrast, if the reaction
nation of the cationic platinum catalyst to the alkyne would proceeded through path (b), then it was envisaged that the 18O
give the activated alkyne A, which would undergo an intramo- atom would be captured as a ketone oxygen. In practice, when
lecular nucleophilic addition reaction with the ester to give B. H218O was added to the reaction mixture instead of H216O
If the R2 substituent was an aryl group, it would stabilize the under the optimal conditions, the reaction gave a mixture of
transition state for the 6-endo cyclization. The ring opening mono-labeled products 13 and 14 along with unlabeled 12a
of cyclic intermediate B would give the allene intermediate C. and di-labeled 15 as a 3:1:3 mixture40,41) (Chart 5, eq. 1). The
The ester would then attacked the central carbon of the allene, treatment of unlabeled 12a with H218O under the optimized
which would be activated by the platinum catalyst, to give
the five membered cyclic intermediates D and E (path a).38)
Intermediates D and E would then be converted to α-acyloxy
ketone H via sequential proto-demetallation39) and hydrolysis
reactions. Substrate 11r reacted much more effectively than
11q (Table 2, entries 16, 17). It would be rationalized that
intermediate F would be readily hydrolyzed by water, because
the presence of an electron withdrawing group on the R1 sub-
stituent would lead to a reduction in the electron density of
the carbonyl carbon. However, an alternative pathway could
occur involving the intermolecular nucleophilic addition of
Fig. 2. Proposed Chelation of the Catalyst to the ortho-Substituent in
Substrates 11l and 11m
Chart 4. Plausible Mechanism with Internal Alkynes
Chart 5. Isotope Labeling Experiments Using H218O

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conditions gave mono-labeled 13 without the hydrolysis of desired α-alkoxyketone 12s albeit in a low yield. This result
the ester (12a:13=7:3, eq. 2). This result indicated that the indicated that the initial 6-exo-dig cyclization could occur to
ketone carbonyl oxygen could be interconverted with water give the product 12s, although the alkyl substituent did not ad-
under the reaction conditions and that di-labeled 15 was most equately stabilize the transition state. Unexpectedly, the reac-
likely produced by addition of H218O to 14 with the elimina- tion of substrate 11t bearing a phenyl group at the propargylic
tion of H216O. The production of 14 therefore suggested that position gave a complex mixture. In contrast, substrate 11u
path (a) was likely to be mechanism for the reaction, however bearing a terminal alkyne and phenyl group at its propargylic
path (b) cannot be ruled out.
position was converted to compound 12u along with a small
To determine the effect of the other substituents on the out- amount of the regioisomer 12u′. Interestingly, the reaction of
come of the reaction, we proceeded to investigate substrates substrate 11v bearing a terminal alkyne and an alkyl group
bearing an alkyl or aryl group on the propargylic position of at its propargylic position gave regioisomer 12v′ as the major
the alkyne (Chart 6). In the case of substrate 11s bearing an product.
alkyl group instead of the aryl group, the reaction gave the
The differences observed in the regioselectivity of these
Chart 6. Switch in the Regioselectivity of the Reaction
Chart 7. Plausible Mechanism with Terminal Alkynes

Vol. 63, No. 9 (2015)
Chem. Pharm. Bull.
715
reactions can be rationalized as follows (Chart 7). Substrates (DMAP) (127.5mg, 1.05mmol) in methylene chloride
containing a terminal alkyne would undergo a 5-exo-dig cy- (CH2Cl2) (50mL) at 0°C was added pivaloyl chloride (1.35mL,
clization rather than a 6-endo-dig cyclization in the absence of 11.0mmol) slowly under Ar and the mixure was warmed to
a cation-stabilizing substituent to give intermediate J. It was room temperature. After stirring for 2h, the mixture was
assumed that the use of a phenyl group as the R1 substituent quenched with water and extracted with chloroform (CHCl3).
would stabilize the partial cation in transition state K to pro- The combined extracts were washed with 1.0M aqueous
duce the platinum carbene L. The subsequent intramolecular solution of HCl and 3.0M aqueous solution of NaOH, dried
addition of the ester to the carbene would give intermedi- over Na2SO4 and concentrated under reduced pressure. The
ate M, which would be converted to α-acyloxyketone 12u obtained residue was purified by silica gel column chroma-
via sequential protodemetallation and hydrolysis reactions. tography (hexane/CH2Cl2=75/25) to give 11a (1.89g, 88%) as
1
In contrast, the use of an alkyl group as the R1 substituent a colorless oil: H-NMR (500MHz, CDCl3) δ: 7.47–7.44 (m,
instead of an aryl group would lead to a reduction in the sta- 2H), 7.35–7.29 (m, 3H), 4.89 (s, 2H), 1.25 (s, 9H); 13C-NMR
bilizing effect of transition state K. Thus, the subsequent pro- (126MHz, CDCl3) δ: 177.9, 131.9, 128.7, 128.3, 122.3, 86.1,
todemetallation and hydrolysis via intermediate O would be 83.3, 52.8, 38.8, 27.1; IR (attenuated total reflectance (ATR))
preferable to give regioisomer 12v′ as the major product rather 2974, 2236, 1279, 1136cm−1; MS (FAB+) m/z=217 ([M+H]+);
than the formation of the carbene intermediate L.
high resolution (HR)-MS (FAB+) Calcd for C14H17O2 [M+H]+:
217.1229. Found: 217.1238.
3-(4-Chlorophenyl)prop-2-yn-1-yl Pivalate (11b)
The reaction was performed according to the proce-
Conclusion
The Pt-catalyzed facial oxidation of alkynes for the synthe-
sis of α-acyloxyketones has been investigated in detail. The dure for 11a. A white solid; 1H-NMR (500MHz, CDCl3)
cationic nature of the platinum catalyst [Pt(cod)Cl2/AgNTf2] δ: 7.39–7.36 (m, 2H), 7.31–7.27 (m, 2H), 4.87 (s, 2H), 1.25
was found to be particularly important for this transforma- (s, 9H); 13C-NMR (126MHz, CDCl3) δ: 177.8, 134.7, 133.1,
tion. The substrate scope of the optimized reaction was 128.6, 120.8, 85.0, 84.3, 52.7, 38.8, 27.1; IR (ATR) 2972, 2234,
investigated as well as the reaction mechanism using H218O. 1726, 1277, 1142, 828cm−1; MS (FAB+) m/z=250 ([M]+);
Taken together, the results of these experiments suggested that HR-MS (FAB+) Calcd for C14H15ClO2 [M]+: 250.0761. Found:
the α-acyloxyketone products were being formed via the Pt- 250.0755.
catalyzed migration of the propargylic ester moiety followed
by the intramolecular nucleophilic addition of the ester to the
allene in intermediate C. This reaction could also be used for dure for 11a. A white solid; H-NMR (500MHz, CDCl3) δ:
3-(4-Bromophenyl)prop-2-yn-1-yl Pivalate (11c)
The reaction was performed according to the proce-
1
the regioselective synthesis of α-aryl-α-acyloxyketones.
7.47–7.43 (m, 2H), 7.33–7.29 (m, 2H), 4.87 (s, 2H), 1.25 (s,
9H); 13C-NMR (126MHz, CDCl3) δ: 177.8, 133.3, 131.6, 123.0,
121.2, 85.0, 84.5, 52.7, 38.8, 27.1; IR (ATR) 2974, 2236, 1733,
Experimental
General Experimental Details Unless otherwise noted, 1486, 1278, 1140, 842cm−1; MS (FAB+) m/z=294 ([M]+);
all reactions were performed under argon. Pt(cod)Cl2 and HR-MS (FAB+) Calcd for C14H1579BrO2 [M]+: 294.0255.
AgNTf2 were purchased from Sigma-Aldrich. Toluene was Found: 294.0265.
purchased from Wako Pure Chemical Industries, Ltd. Un-
less otherwise noted, all other reagents were purchased from
commercial suppliers and used as received. Propargyl alco- for 11a. A white solid: mp 58.1–58.9°C; H-NMR (500MHz,
hols were prepared according to the known procedures using CDCl3) δ: 7.99 (d, 2H, J=8.0Hz), 7.51 (d, 2H, J=8.0Hz), 4.90
Sonogashira coupling with 2-propyn-1-ol and aryl iodides or (s, 2H), 3.92 (s, 3H), 1.25 (s, 9H); 13C-NMR (126MHz, CDCl3)
Methyl 4-(3-(Pivaloyloxy)prop-1-yn-1-yl)benzoate (11d)
The reaction was performed according to the procedure
1
nucleophilic addition of terminal alkynes to aldehydes.
δ: 177.8, 166.4, 131.8, 129.9, 129.4, 126.9, 86.3, 85.3, 52.6, 52.3,
Analytical thin-layer chromatography was performed with 38.8, 27.1; IR (ATR) 2969, 2240, 1720, 1273, 1144, 862cm−1;
Merck Silica gel 60. Silica gel column chromatography was MS (FAB+) m/z=275 ([M+H]+); HR-MS (FAB+) Calcd for
performed with Kanto silica gel 60 (particle size, 63–210µm) C16H19O4 [M+H]+: 275.1283. Found: 275.1284.
or Fuji Silysia BW-300. All melting points (mp) were deter-
mined on BÜCHI Melting Point M-565. Proton nuclear mag-
3-(4-Cyanophenyl)prop-2-yn-1-yl Pivalate (11e)
The reaction was performed according to the procedure
netic resonance (1H-NMR) spectra were recorded on a JEOL for 11a. An orange oil; 1H-NMR (500MHz, CDCl3) δ:
JNM-LA 500 at 500MHz. Chemical shifts are reported rela- 7.63–7.60 (m, 2H), 7.54–7.52 (m, 2H), 4.90 (s, 2H), 1.25 (s,
tive to Me4Si (δ 0.00). Multiplicity is indicated by one or more 9H); 13C-NMR (126MHz, CDCl3) δ: 177.7, 132.4, 132.0, 127.2,
of the following: s (singlet); d (doublet); t (triplet); q (quartet); 118.3, 112.1, 87.8, 84.3, 52.4, 38.8, 27.1; IR (ATR) 2974, 2229,
sep (septet); m (multiplet); br (broad). Carbon nuclear mag- 1732, 1278, 1134, 840cm−1; MS (FAB+) m/z=242 ([M+H]+);
netic resonance (13C-NMR) spectra were recorded on a JEOL HR-MS (FAB+) Calcd for C15H16NO2 [M+H]+: 242.1181.
JNM-LA 500 at 126MHz. Chemical shifts are reported rela- Found: 242.1178.
tive to chloroform-d3 (CDCl3) (δ 77.0). Infrared spectra were
3-(4-Nitrophenyl)prop-2-yn-1-yl Pivalate (11f)
recorded on a Fourier transform (FT)/IR-4100 (JASCO). Low
The reaction was performed according to the proce-
and high resolution mass spectra were recorded on JEOL dure for 11a. A yellow oil; 1H-NMR (500MHz, CDCl3) δ:
JMS-HX/HX 110A.
8.21–8.17 (m, 2H), 7.61–7.58 (m, 2H), 4.92 (s, 2H), 1.26 (s,
9H); 13C-NMR (126MHz, CDCl3) δ: 177.7, 147.3, 132.6, 129.1,
123.5, 88.7, 84.1, 52.4, 38.8, 27.1; IR (ATR) 2975, 1734, 1520,
Preperation of Propargyl Esters
3-Phenylprop-2-yn-1-yl Pivalate (11a)42)
To the solution of 3-phenyl-2-propyn-1-ol (1.32g, 10.0mmol), 1343, 1278, 1136, 854cm−1; MS (FAB+) m/z=262 ([M+H]+);
NEt3 (7.0mL, 50.0mmol) and 4-(dimethylamino)pyridine HR-MS (FAB+) Calcd for C14H16NO4 [M+H]+: 262.1079.

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Found: 262.1082.
177.8, 149.7, 134.9, 132.8, 129.0, 124.6, 117.7, 91.4, 81.3, 52.6,
38.8, 27.1; IR (ATR) 2975, 1735, 1529, 1345, 1280, 1141cm−1;
3-(4-(Trifluoromethyl)phenyl)prop-2-yn-1-yl Pivalate (11g)
The reaction was performed according to the procedure for MS (FAB+) m/z=262 ([M+H]+); HR-MS (FAB+) Calcd for
11a. A colorless oil; H-NMR (500MHz, CDCl3) δ: 7.59–7.53 C14H16NO4 [M+H]+: 262.1079. Found: 262.1078.
1
(m, 4H), 4.90 (s, 2H), 1.25 (s, 9H); 13C-NMR (126MHz,
3-Phenylprop-2-yn-1-yl Acetate (11n)43)
CDCl3) δ: 177.8, 132.1, 130.4 (q, J=32.4Hz), 126.1, 125.2 (q,
The reaction was performed according to the procedure
J=3.6Hz), 123.8 (q, J=272.3Hz), 85.8, 84.7, 52.5, 38.8, 27.1; for 11a. A colorless oil; 1H-NMR (500MHz, CDCl3) δ:
IR (ATR) 2977, 1734, 1321, 1278, 1125, 842cm−1; MS (FAB+) 7.47–7.44 (m, 2H), 7.36–7.29 (m, 3H), 4.91 (s, 2H), 2.14 (s,
m/z=284 ([M]+); HR-MS (FAB+) Calcd for C15H15F3O2 [M]+: 3H); 13C-NMR (126MHz, CDCl3) δ: 170.3, 131.9, 128.8, 128.3,
284.1024. Found: 284.1017.
122.1, 86.4, 82.9, 52.8, 20.8; IR (ATR) 2939, 2240, 1747, 1225,
3-(p-Tolyl)prop-2-yn-1-yl Pivalate (11h)
1034 cm−1; MS (FAB+) m/z=174 ([M]+); HR-MS (FAB+) Calcd
The reaction was performed according to the procedure for for C11H10O2 [M]+: 174.0681. Found: 174.0682.
1
11a. A white solid; H-NMR (500MHz, CDCl3) δ: 7.35 (d,
2H, J=8.0Hz), 7.12 (d, 2H, J=8.0Hz), 4.88 (s, 2H), 2.40 (s,
3-Phenylprop-2-yn-1-yl Isobutyrate (11o)
The reaction was performed according to the procedure for
3H), 1.24 (s, 9H); 13C-NMR (126MHz, CDCl3) δ: 177.9, 138.8, 11a. A colorless oil; H-NMR (500MHz, CDCl3) δ: 7.47–7.44
131.8, 129.0, 119.2, 86.3, 82.6, 52.9, 38.8, 27.1, 21.5; IR (ATR) (m, 2H), 7.36–7.29 (m, 3H), 4.91 (s, 2H), 2.67–2.59 (m, 1H),
2978, 2235, 1721, 1278, 1148, 822cm−1; MS (FAB+) m/z=231 1.21 (d, 6H, J=7.2Hz); 13C-NMR (126MHz, CDCl3) δ: 176.5,
([M+H]+); HR-MS (FAB+) Calcd for C15H19O2 [M+H]+: 131.9, 128.7, 128.3, 122.2, 86.3, 83.1, 52.7, 33.9, 18.9; IR (ATR)
1
231.1385. Found: 231.1385.
3-(4-Methoxyphenyl)prop-2-yn-1-yl Pivalate (11i)
2976, 2238, 1740, 1148cm−1; MS (FAB+) m/z=202 ([M]+);
HR-MS (FAB+) Calcd for C13H14O2 [M]+: 202.0994. Found:
The reaction was performed according to the procedure for 202.0997.
1
11a. A colorless oil; H-NMR (500MHz, CDCl3) δ: 7.41–7.38
3-Phenylprop-2-yn-1-yl Benzoate (11p)44)
The reaction was performed according to the procedure for
(m, 2H), 6.85–6.82 (m, 2H), 4.88 (s, 2H), 3.81 (s, 3H), 1.24 (s,
9H); 13C-NMR (126MHz, CDCl3) δ: 177.9, 159.8, 133.4, 114.3, 11a. A colorless oil; H-NMR (500MHz, CDCl3) δ: 8.13–8.08
113.9, 86.1, 81.2, 55.2, 53.0, 38.8, 27.1; IR (ATR) 2972, 2231, (m, 2H), 7.60–7.56 (m, 1H), 7.50–7.43 (m, 4H), 7.36–7.29 (m,
1732, 1510, 1249, 1140, 1034, 833cm−1; MS (FAB+) m/z=247 3H), 5.16 (s, 2H); 13C-NMR (126MHz, CDCl3) δ: 165.9, 133.2,
([M+H]+); HR-MS (FAB+) Calcd for C15H19O3 [M+H]+: 131.9, 129.8, 129.6, 128.7, 128.4, 128.3, 122.2, 86.6, 83.0,
1
247.1334. Found: 247.1328.
53.3; IR (ATR) 3064, 2944, 2232, 1727, 1271, 1108cm−1; MS
3-(3-Methoxyphenyl)prop-2-yn-1-yl Pivalate (11j)
(FAB+) m/z=236 ([M]+); HR-MS (FAB+) Calcd for C16H12O2
The reaction was performed according to the procedure for [M]+: 236.0837. Found: 236.0841.
1
11a. A colorless oil; H-NMR (500MHz, CDCl3) δ: 7.22 (dd,
1H, J=8.0Hz), 7.05 (d, 1H, J=8.0Hz), 6.89 (d, 1H, J=8.0Hz),
3-Phenylprop-2-yn-1-yl 4-Methoxybenzoate (11q)
The reaction was performed according to the procedure for
4.89 (s, 2H), 3.80 (s, 3H), 1.25 (s, 9H); 13C-NMR (126MHz, 11a. A colorless oil; H-NMR (500MHz, CDCl3) δ: 8.08–8.04
CDCl3) δ: 177.8, 159.2, 129.3, 124.4, 123.2, 116.6, 115.3, 86.0, (m, 2H), 7.50–7.46 (m, 2H), 7.36–7.29 (m, 3H), 6.95–6.91 (m,
83.1, 55.3, 52.8, 38.8, 27.1; IR (ATR) 2973, 2240, 1735, 1481, 2H), 5.13 (s, 2H), 3.87 (s, 3H); 13C-NMR (126MHz, CDCl3) δ:
1292, 1144, 1048, 787cm−1; MS (FAB+) m/z=246 ([M]+); 165.7, 163.6, 131.9, 128.7, 128.3, 122.2, 122.0, 113.6, 86.4, 83.3,
HR-MS (FAB+) Calcd for C15H18O3 [M]+: 246.1256. Found: 55.4, 53.0 (one carbon is missing); IR (ATR) 3057, 2936, 2229,
1
246.1260.
3-(3-Nitrophenyl)prop-2-yn-1-yl Pivalate (11k)
1716, 1605, 1257, 1168, 1098, 1030cm−1; MS (FAB+) m/z=266
([M]+); HR-MS (FAB+) Calcd for C17H14O3 [M]+: 266.0943.
The reaction was performed according to the procedure for Found: 266.0948.
1
11a. A colorless oil; H-NMR (500MHz, CDCl3) δ: 8.30 (s,
1H), 8.19 (d, 1H, J=8.1Hz), 7.75 (d, 1H, J=8.1Hz), 7.51 (dd,
3-Phenylprop-2-yn-1-yl 4-Nitrobenzoate (11r)
The reaction was performed according to the procedure
1H, J=8.1Hz), 4.91 (s, 2H), 1.26 (s, 9H); 13C-NMR (126MHz, for 11a. A yellow solid: mp 59.0–60.1°C; H-NMR (500MHz,
CDCl3) δ: 177.8, 148.0, 137.5, 129.3, 126.7, 124.1, 123.4, 86.1, CDCl3) δ: 8.34–8.26 (m, 4H), 7.51–7.46 (m, 2H), 7.38–7.31 (m,
83.6, 52.4, 38.8, 27.1; IR (ATR) 2973, 1733, 1532, 1350, 1279, 3H), 5.21 (s, 2H); 13C-NMR (126MHz, CDCl3) δ: 164.1, 150.7,
1138 cm−1; MS (FAB+) m/z=261 ([M]+); HR-MS (FAB+) Calcd 135.0, 131.9, 131.0, 129.0, 128.4, 123.6, 121.8, 87.2, 82.2, 54.2;
1
for C14H15NO4 [M]+: 261.1001. Found: 261.0994.
IR (ATR) 3112, 2955, 2230, 1719, 1526, 1347, 1263, 1097cm−1;
3-(2-Methoxyphenyl)prop-2-yn-1-yl Pivalate (11l)
MS (FAB+) m/z=281 ([M]+); HR-MS (FAB+) Calcd for
The reaction was performed according to the procedure for C16H11NO4 [M]+: 281.0688. Found: 281.0692.
1
11a. A brown oil; H-NMR (500MHz, CDCl3) δ: 7.44–7.41
5-Phenylpent-2-yn-1-yl Pivalate (11s)
(m, 1H), 7.33–7.28 (m, 1H), 6.93–6.86 (m, 2H), 4.94 (s, 2H),
The reaction was performed according to the procedure
3.88 (s, 3H), 1.25 (s, 9H); 13C-NMR (126MHz, CDCl3) δ: for 11a. A colorless oil; 1H-NMR (500MHz, CDCl3) δ:
177.9, 160.1, 134.0, 130.1, 120.4, 111.4, 110.6, 87.3, 82.5, 55.8, 7.32–7.27 (m, 2H), 7.24–7.20 (m, 3H), 4.65–4.63 (m, 2H), 2.83
53.1, 38.8, 27.1; IR (ATR) 2972, 2237, 1732, 1494, 1266, 1143, (t, 2H, J=7.6Hz), 2.53–2.49 (m, 2H), 1.22 (s, 9H); 13C-NMR
1026 cm−1; MS (FAB+) m/z=247 ([M+H]+); HR-MS (FAB+) (126MHz, CDCl3) δ: 177.9, 140.4, 128.4, 128.4, 126.3, 86.3,
Calcd for C15H19O3 [M+H]+: 247.1334. Found: 247.1336.
3-(2-Nitrophenyl)prop-2-yn-1-yl Pivalate (11m)
75.0, 52.7, 38.7, 34.8, 27.1, 21.0; IR (ATR) 2974, 2235, 1735,
1280, 1146cm−1; MS (FAB+) m/z=245 ([M+H]+); HR-MS
The reaction was performed according to the procedure for (FAB+) Calcd for C16H21O2 [M+H]+: 245.1542. Found:
1
11a. A yellow oil; H-NMR (500MHz, CDCl3) δ: 8.07–8.04 245.1542.
(m, 1H), 7.65–7.62 (m, 1H), 7.60–7.56 (m, 1H), 7.50–7.46 (m,
1,3-Diphenylprop-2-yn-1-yl Pivalate (11t)42)
The reaction was performed according to the procedure for
1H), 4.95 (s, 2H), 1.27 (s, 9H); 13C-NMR (126MHz, CDCl3) δ:

Vol. 63, No. 9 (2015)
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717
1
11a. A colorless oil; H-NMR (500MHz, CDCl3) δ: 7.59–7.55 CDCl3) δ: 201.6, 177.6, 132.5, 132.1, 129.2, 123.4, 79.9, 38.7,
(m, 2H), 7.48–7.45 (m, 2H), 7.42–7.28 (m, 6H), 6.67 (s, 1H), 27.0, 25.9; IR (ATR) 2974, 1725, 1487, 1140cm−1; MS (FAB+)
1.24 (s, 9H); 13C-NMR (126MHz, CDCl3) δ: 177.2, 137.5, m/z=313 ([M+H]+); HR-MS (FAB+) Calcd for C14H1879BrO3
131.9, 128.7, 128.7, 128.6, 128.2, 127.4, 122.2, 86.7, 85.8, 65.8, [M+H]+: 313.0439. Found: 313.0432.
38.8, 27.0 ; IR (ATR) 2972, 2231, 1733, 1273, 1138cm−1; MS
(FAB+) m/z=292 ([M]+); HR-MS (FAB+) Calcd for C20H20O2
[M]+: 292.1463. Found: 292.1462.
Methyl 4-(2-Oxo-1-(pivaloyloxy)propyl)benzoate (12d)
The reaction was performed according to the procedure for
1
12a and gave 12d in 82% yield as a colorless oil; H-NMR
1-Phenylprop-2-yn-1-yl Pivalate (11u)45)
(500MHz, CDCl3) δ: 8.08 (d, 2H, J=8.6Hz), 7.51 (d, 2H,
The reaction was performed according to the procedure for J=8.6Hz), 5.98 (s, 1H), 3.93 (s, 3H), 2.14 (s, 3H), 1.30 (s, 9H);
1
11a. A colorless oil; H-NMR (500MHz, CDCl3) δ: 7.53–7.49 13C-NMR (126MHz, CDCl3) δ: 201.5, 177.5, 166.4, 138.3,
(m, 2H), 7.41–7.34 (m, 3H), 6.42 (d, 1H, J=2.3Hz), 2.62 (d, 130.8, 130.1, 127.4, 80.1, 52.2, 38.7, 27.0, 25.9; IR (ATR)
1H, J=2.3Hz), 1.22 (s, 9H); 13C-NMR (126MHz, CDCl3) δ: 2975, 1726, 1281, 1146cm−1; MS (FAB+) m/z=293 ([M+H]+);
177.1, 136.8, 128.8, 128.6, 127.2, 80.4, 75.1, 65.0, 38.7, 26.9; IR HR-MS (FAB+) Calcd for C16H21O5 [M+H]+: 293.1389. Found:
(ATR) 3290, 2974, 1736, 1270, 1141cm−1; MS (FAB+) m/z=216 293.1389.
([M+]); HR-MS (FAB+) Calcd for C14H16O2 [M]+: 216.1150.
Found: 216.1149.
5-Phenylpent-1-yn-3-yl Pivalate (11v)
1-(4-Cyanophenyl)-2-oxopropyl Pivalate (12e)
The reaction was performed according to the procedure for
12a and gave 12e in 81% yield as a colorless oil; H-NMR
1
The reaction was performed according to the procedure (500MHz, CDCl3) δ: 7.73–7.70 (m, 2H), 7.58–7.54 (m, 2H),
for 11a. A colorless oil; 1H-NMR (500MHz, CDCl3) δ: 5.97 (s, 1H), 2.17 (s, 3H), 1.31 (s, 9H); 13C-NMR (126MHz,
7.31–7.27 (m, 2H), 7.23–7.17 (m, 3H), 5.33 (td, 1H, J1=2.0Hz, CDCl3) δ: 201.3, 177.3, 138.6, 132.6, 128.0, 118.1, 113.0,
J2=6.6Hz), 2.83–2.73 (m, 2H), 2.47 (d, 1H, J=2.0Hz), 79.7, 38.7, 27.0, 26.0; IR (ATR) 2975, 2230, 1728, 1140cm−1;
2.17–2.04 (m, 2H), 1.23 (s, 9H); 13C-NMR (126MHz, CDCl3) MS (FAB+) m/z=260 ([M+H]+); HR-MS (FAB+) Calcd for
δ: 177.3, 140.7, 128.5, 128.4, 126.2, 81.1, 73.5, 63.0, 38.7, 36.2, C15H18NO3 [M+H]+: 260.1287. Found: 260.1289.
31.1, 27.0; IR (ATR) 3293, 2974, 1735, 1279, 1146cm−1; MS
(FAB+) m/z=245 ([M+]); HR-MS (FAB+) Calcd for C16H21O2
[M]+: 245.1542. Found: 245.1547.
1-(4-Nitrophenyl)-2-oxopropyl Pivalate (12f)
The reaction was performed according to the procedure
for 12a and gave 12f in 84% yield as a yellow oil; H-NMR
1
General Procedure for the Synthesis of α-Acyloxyketone (500MHz, CDCl3) δ: 8.27 (d, 2H, J=8.6Hz), 7.63 (d, 2H,
2-Oxo-1-phenylpropyl Pivalate (12a)
J=8.6Hz), 6.02 (s, 1H), 2.19 (s, 3H), 1.32 (s, 9H); 13C-NMR
To the solution of Pt(cod)Cl2 (3.4mg, 0.009mmol), AgNTf2 (126MHz, CDCl3) δ: 201.2, 177.3, 148.2, 140.5, 128.2, 124.1,
(3.5mg, 0.009mmol) and H2O (16µL, 0.9mmol) in toluene 79.5, 38.8, 27.0, 26.0; IR (ATR) 2976, 1729, 1524, 1348,
(4mL) at 0°C was added 3-phenylprop-2-yn-1-yl pivalate 1a 1140 cm−1; MS (FAB+) m/z=280 ([M+H]+); HR-MS (FAB+)
(64.9mg, 0.3mmol) dissolved in toluene (0.5mL) using sy- Calcd for C14H18NO5 [M+H]+: 280.1185. Found: 280.1180.
ringe. After three repeats of rinsing the syringe with toluene
(0.5mL) and addition of the rinsed solution to the reaction
2-Oxo-1-(4-(trifluoromethyl)phenyl)propyl Pivalate (12g)
The reaction was performed according to the procedure for
1
mixture, the mixture was warmed to room temperature. After 12a and gave 12g in 89% yield as a colorless oil; H-NMR
stirring for 30min at the same temperature, the mixture was (500MHz, CDCl3) δ: 7.67 (d, 2H, J=8.0Hz), 7.57 (d, 2H,
warmed to 100°C. When the starting material disappeared J=8.0Hz), 5.98 (s, 1H), 2.16 (s, 3H), 1.31 (s, 9H); 13C-NMR
(checked by TLC), the reaction mixture was cooled to room (126MHz, CDCl3) δ: 201.5, 177.5, 137.5, 131.2 (q, J=32.8Hz),
temperature and concentrated under reduced pressure. The 127.0, 125.9 (q, J=4.0Hz), 123.8 (q, J=272.3Hz), 79.9, 38.8,
obtained residue was purified by silica gel column chroma- 27.0, 25.9; IR (ATR) 2979, 1733, 1326, 1137cm−1; MS (FAB+)
tography (hexane/EtOAc=97.5/2.5) to give 12a (46.8mg, 67%) m/z=303 ([M+H]+); HR-MS (FAB+) Calcd for C15H18F3O3
1
as a colorless oil.: H-NMR (500MHz, CDCl3) δ: 7.45–7.36 [M+H]+: 303.1208. Found: 303.1196.
(m, 5H), 5.92 (s, 1H), 2.12 (s, 3H), 1.29 (s, 9H); 13C-NMR
2-Oxo-1-(p-tolyl)propyl Pivalate (12h)
(126MHz, CDCl3) δ: 202.0, 177.8, 133.5, 129.1, 129.0, 127.6,
The reaction was performed according to the procedure
1
80.7, 38.7, 27.1, 25.9; IR (ATR) 2974, 1725, 1146cm−1; MS for 12a and gave 12h in 47% yield as a yellow oil: H-NMR
(FAB+) m/z=235 ([M+H]+); HR-MS (FAB+) Calcd for (500MHz, CDCl3) δ: 7.30 (d, 2H, J=8.0Hz), 7.21 (d, 2H,
C14H18O3 [M+H]+: 235.1334. Found: 235.1337.
1-(4-Chlorophenyl)-2-oxopropyl Pivalate (12b)
J=8.0Hz), 5.88 (s, 1H), 2.36 (s, 3H), 2.11 (s, 9H); 13C-NMR
(126MHz, CDCl3) δ: 202.1, 177.9, 139.1, 130.5, 129.6, 127.6,
The reaction was performed according to the procedure for 80.5, 38.7, 27.1, 25.9, 21.2; IR (ATR) 2975, 1729, 1146cm−1;
1
12a and gave 12b in 77% yield as a colorless oil; H-NMR MS (FAB+) m/z=249 ([M+H]+); HR-MS (FAB+) Calcd for
(500MHz, CDCl3) δ: 7.40–7.34 (m, 4H), 5.89 (s, 1H), 2.12 (s, C15H21O3 [M+H]+: 249.1491. Found: 249.1494.
3H), 1.29 (s, 9H); 13C-NMR (126MHz, CDCl3) δ: 201.7, 177.6,
1-(3-Methoxyphenyl)-2-oxopropyl Pivalate (12j)
135.2, 132.0, 129.2, 128.9, 79.8, 38.7, 27.0, 25.9; IR (ATR)
The reaction was performed according to the procedure for
1
2975, 1728, 1491, 1147cm−1; MS (FAB+) m/z=269 ([M+H]+); 12a and gave 12j in 58% yield as a colorless oil; H-NMR
HR-MS (FAB+) Calcd for C14H18ClO3 [M+H]+: 269.0944. (500MHz, CDCl3) δ: 7.31 (dd, 1H, J=7.9Hz), 7.01 (d, 1H,
Found: 269.0940.
1-(4-Bromophenyl)-2-oxopropyl Pivalate (12c)
J=7.9Hz), 6.96–6.90 (m, 2H), 5.89 (s, 1H), 3.82 (s, 3H),
2.12 (s, 3H), 1.29 (s, 9H); 13C-NMR (126MHz, CDCl3) δ:
The reaction was performed according to the procedure for 201.9, 177.7, 159.9, 134.9, 130.0, 119.9, 114.5, 113.1, 80.5, 55.2,
1
12a and gave 12c in 69% yield as a colorless oil; H-NMR 38.7, 27.1, 25.8; IR (ATR) 2973, 1727, 1277, 1147, 1042cm−1;
(500MHz, CDCl3) δ: 7.56–7.50 (m, 2H), 7.32–7.28 (m, 2H), MS (FAB+) m/z=265 ([M+H]+); HR-MS (FAB+) Calcd for
5.87 (s, 1H), 2.13 (s, 3H), 1.28 (s, 9H); 13C-NMR (126MHz, C15H21O4 [M+H]+: 265.1440. Found: 265.1436.

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Vol. 63, No. 9 (2015)
1-(3-Nitrophenyl)-2-oxopropyl Pivalate (12k)
(m, 3H), 4.95 (dd, 1H, J1=8.6Hz, J2=4.3Hz), 2.78–2.64 (m,
The reaction was performed according to the proce- 2H), 2.15–2.02 (m, 5H), 1.29 (s, 9H); 13C-NMR (126MHz,
dure for 12a and gave 12k in 84% yield as a colorless oil; CDCl3) δ: 205.5, 177.9, 140.4, 128.6, 128.4, 126.3, 77.7,
1H-NMR (500MHz, CDCl3) δ: 8.32–8.23 (m, 2H), 7.78 (d, 38.8, 32.0, 31.4, 27.1, 26.0; IR (ATR) 2972, 1729, 1151cm−1;
1H, J=8.0Hz), 7.62 (dd, 1H, J=8.0Hz), 6.03 (s, 1H), 2.21 MS (FAB+) m/z=263 ([M+H]+); HR-MS (FAB+) Calcd for
(s, 3H), 1.32 (s, 9H); 13C-NMR (126MHz, CDCl3) δ: 201.5, C16H23O3 [M+H]+: 263.1647. Found: 263.1656.
177.3, 148.5, 135.8, 133.4, 130.0, 123.9, 122.2, 79.3, 38.8, 27.0,
2-Oxo-3-phenylpropyl Pivalate (12u)
The reaction was performed according to the procedure for
26.1; IR (ATR) 2975, 1729, 1533, 1351, 1142cm−1; MS (FAB+)
m/z=280 ([M+H]+); HR-MS (FAB+) Calcd for C14H18NO5 12a and gave 12u in 41% NMR yield (containing 10% NMR
[M+H]+: 280.1185. Found: 280.1190.
2-Oxo-1-phenylpropyl Acetate (12n)46)
yield of 12u′) as a colorless oil; H-NMR (500MHz, CDCl3)
δ: 7.35–7.19 (m, 5H), 4.68 (s, 2H), 3.73 (s, 2H), 1.25 (s, 9H);
1
The reaction was performed according to the procedure for 13C-NMR (126MHz, CDCl3) δ: 201.2, 177.7, 132.8, 129.4,
1
12a and gave 12n in 35% yield as a colorless oil; H-NMR 128.7, 127.2, 67.4, 46.1, 38.6, 27.0; IR (ATR) 2975, 1732, 1285,
(500MHz, CDCl3) δ: 7.43–7.40 (m, 5H), 5.98 (s, 1H), 2.20 1158 cm−1; MS (FAB+) m/z=235 ([M+H]+); HR-MS (FAB+)
(s, 3H), 2.11 (s, 3H); 13C-NMR (126MHz, CDCl3) δ: 201.7, Calcd for C14H19O3 [M+H]+: 235.1334. Found: 235.1333.
170.3, 133.1, 129.4, 129.1, 128.1, 80.9, 26.1, 20.7; IR (ATR)
2-Oxo-5-phenylpentyl Pivalate (12v)
The reaction was performed according to the procedure for
2934, 1733, 1234cm−1; MS (FAB+) m/z=193 ([M+H]+);
HR-MS (FAB+) Calcd for C11H13O3 [M+H]+: 193.0865. Found: 12a and gave 12v in 8% NMR yield (containing 73% NMR
193.0865.
2-Oxo-1-phenylpropyl Isobutyrate (12o)
yield of 12v′) as a colorless oil. These products couldn’t
be isolated from each other, so 1H-NMR of the mixtures
The reaction was performed according to the proce- (in a ratio of 12v:12v′=0.11:1.00) was reported; 1H-NMR
dure for 12a and gave 12o in 48% yield as a colorless oil; (500MHz, CDCl3) δ: 7.27–7.31 (m, 2.22H, 12v+12v′),
1H-NMR (500MHz, CDCl3) δ: 7.44–7.38 (m, 5H), 5.95 (s, 7.23–7.15 (m, 3.33H, 12v+12v′), 4.95 (dd, 1H, J1=8.6Hz,
1H), 2.75–2.67 (m, 1H), 2.12 (s, 3H), 1.28 (d, 3H, J=7.2Hz), J2=4.3Hz, 12v′), 4.58 (s, 0.22H, 12v), 2.78–2.62 (m, 2.22H,
1.21 (d, 3H, J=7.2Hz); 13C-NMR (126MHz, CDCl3) δ: 201.9, 12v+12v′), 2.40 (t, 0.22H, J=7.3Hz, 12v), 2.15–2.02 (m, 5H,
176.4, 133.3, 129.2, 129.0, 127.9, 80.6, 33.8, 26.0, 19.0, 18.7; IR 12v′), 1.99–1.91 (m, 0.22H, 12v), 1.29 (s, 9H, 12v′), 1.25 (s,
(ATR) 2976, 1728, 1149cm−1; MS (FAB+) m/z=221 ([M+H]+); 0.99H, 12v′). Compound 12v′ is the same as compound 12s.
HR-MS (FAB+) Calcd for C13H17O3 [M+H]+: 221.1178. Found:
221.1181.
Acknowledgments This work was supported by a Grant-
in-Aid for Scientific Research on Innovative Areas “Mo-
2-Oxo-1-phenylpropyl Benzoate (12p)47)
The reaction was performed according to the procedure for lecular Activation Directed toward Straightforward Synthesis”
1
12a and gave 12p in 32% yield as a colorless oil: H-NMR (25105727) and Platform for Drug Discovery, Informatics, and
(500MHz, CDCl3) δ: 8.12 (d, 2H, J=8.0Hz), 7.61–7.40 (m, Structural Life Science from the Ministry of Education, Cul-
8H), 6.20 (s, 1H), 2.20 (s, 3H); 13C-NMR (126MHz, CDCl3) ture, Sports, Science and Technology (MEXT) of Japan.
δ: 201.8, 165.8, 133.5, 133.4, 129.9, 129.3, 129.2, 129.1, 128.5,
127.9, 81.3, 26.1; IR (ATR) 3064, 1721, 1277, 1110cm−1;
Conflict of Interest The authors declare no conflict of
MS (FAB+) m/z=255 ([M+H]+); HR-MS (FAB+) Calcd for interest.
C16H15O3 [M+H]+: 255.1021. Found: 255.1019.
2-Oxo-1-phenylpropyl 4-Methoxybenzoate (12q)
Supplementary Materials The online version of this ar-
The reaction was performed according to the procedure for ticle contains supplementary materials.
1
12a and gave 12q in 14% yield as a colorless oil: H-NMR
(500MHz, CDCl3) δ: 8.08 (d, 2H, J=8.6Hz), 7.55–7.38 (m,
5H), 6.94 (d, 2H, J=8.6Hz), 6.17 (s, 1H), 3.87 (s, 3H), 2.19
(s, 3H); 13C-NMR (126MHz, CDCl3) δ: 202.2, 165.5, 163.8,
133.6, 132.0, 129.2, 129.1, 127.9, 121.6, 113.7, 81.0, 55.5, 26.0;
IR (ATR) 3066, 2934, 1714, 1607, 1259, 1168, 1102, 1029cm−1;
MS (FAB+) m/z=285 ([M+H]+); HR-MS (FAB+) Calcd for
C17H16O4 [M+H]+: 285.1127. Found: 285.1121.
References and Notes
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1
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1
12a and gave 12s in 21% yield as a colorless oil; H-NMR
(500MHz, CDCl3) δ: 7.29 (dd, 2H, J1=J2=7.7 Hz), 7.23–7.15

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