Transition metal-free oxidation of ynamides for synthesis of α-keto-imides

Article abstract of DOI:10.1016/j.tet.2014.04.080

Transition metal-free double oxidation of triple bonds in ynamides for synthesis of α-keto-imides is described. The successful key was combination of NIS and DMSO under atmospheric air in CPME solvent, and the reaction quickly proceeds at 0 °C within 1 h.

Full text of DOI:10.1016/j.tet.2014.04.080

Tetrahedron 70 (2014) 3988e3993
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journal homepage: www.elsevier.com/locate/tet
Transition metal-free oxidation of ynamides for synthesis of
imides
a-keto-
*
Takuya Chikugo, Yuta Yauchi, Masataka Ide, Tetsuo Iwasawa
Department of Materials Chemistry, Faculty of Science and Technology, Ryukoku University, Otsu, Shiga 520-2194, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Transition metal-free double oxidation of triple bonds in ynamides for synthesis of
a-keto-imides is
Received 13 March 2014
Received in revised form 25 April 2014
Accepted 26 April 2014
described. The successful key was combination of NIS and DMSO under atmospheric air in CPME solvent,
and the reaction quickly proceeds at 0 ꢀC within 1 h. Although the yields and substrate generality are
moderate, yet the prototype protocol avoids the use of expensive, moisture-sensitive, toxic, and explosive
additives, which make it potentially and significantly greener than current alternatives.
Ó 2014 Elsevier Ltd. All rights reserved.
Available online 2 May 2014
Keywords:
Oxidation
a
-Keto-imide
1,2-Diketone
Ynamide
Transition metal-free reaction
1. Introduction
both RuO2eNaIO4 and DMDO (dimethyldioxirane) oxidations, that
is, the each procedure also consists of the transition metal approach
One significant goal in modern synthetic organic chemistry is
the development of efficient and sustainable processes capable or
replacing hazardous classical reactions.1e3 The oxidation of organic
molecules is a traditional and fundamental reaction that depends
on harmful metals and dangerous oxidants.4 Although transition
metal-protocols and exquisitely elaborated oxidants are successful
for oxidation reaction,5 they usually have inherent limitations, such
as moisture sensitivity, environmentally toxicity, costly materials,
and potentially explosive.6 Moreover, separation of metals from
polar products, which is of particular importance for the synthesis
of pharmaceutical fine chemicals because of their residual toxicity
in the target drugs, is a critical issue to consider.7 Hence, it is pur-
poseful to exploit transition metal-free approach and handling-
easy oxidant invention.
Recently we have developed the regio- and stereoselective
iodobromination and hydrohalogenation of ynamides to synthesize
varied haloenamides on diverse scaffolds.8 In the course of our
study, we encountered the unforeseen oxidation reaction (Eq. 1):
ynamide 1 was transformed into a-keto-imides 2 in 70% yield un-
der just NIS (N-iodosuccinimide)/DMSO (dimethyl sulfoxide) con-
and the labile oxidant system.9 As a consequence, we immediately
began exploring the scope and limitation of this transformation.
Although the
the limited protocol, its significance lies in the close analogy to
keto-amide and -keto-ester. The -keto-imide has at least one
a-keto-imide is underrepresented so far owing to
a
-
a
a
electron-withdrawing group (EWG) on the nitrogen atom, which
makes it more thermodynamically stable than the corresponding
a-keto-amide: still, the a-keto-imide is well reactive. Actually,
some successful transformations have been achieved on hetero-
DielseAlder reactions,10a and diastereoselective allylation,10b and
Grignard-addition reaction.10c As the
a-keto-amide and ester are
capable of participating a wide range of complexity-generating
transformations (e.g., stereochemical-controlled addition of
nucleophiles,10d and pinacol-type couplings,10e and photo-
dition. So far only Hsung and co-workers elegantly achieved the
direct oxidation of ynamides to a-keto-imides, and they employed
cyclization to
tially work as a diverse synton. In addition, from the biological
point of view, the -keto-amide is responsible for several enzy-
matic reactions11 and pharmaceutical function as an enzymatic
b a-keto-imide also would poten-
-lactams10f), the
a
* Corresponding author. Tel.: þ81 77 543 7461; fax: þ81 77 543 7483; e-mail
address: iwasawa@rins.ryukoku.ac.jp (T. Iwasawa).
0040-4020/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2014.04.080

T. Chikugo et al. / Tetrahedron 70 (2014) 3988e3993
3989
inhibitor.12 Thus, the similarity strongly implies how valuable role
a facile route to -keto-imide performs. On the other hand, unlike
-keto-imide, the importance of diarylalkynes (benzils) is well
known to underlie the many research fields of science. For example,
such benzils are employed as the critical synthetic intermediates in
material science13 and medicinal chemistry;14 however, synthetic
availability of unsymmetrical benzils remains a challenge. The
Next we examined the effect of iodine sources and other halo-
gens on the oxidation as shown in Table 2. When the employment
of NIS decreased to 0.6 equiv, the yield reduced to 63% (entry 2); the
oxidation required stoichiometric amount of NIS (entry 1). For
entries 3e5, actions of I2 were attempted18 and nearly complete
consumption of the starting ynamide 1 was observed; however, the
high yielding transformations were not achieved. For entries 6 and
7, the additives of KI and NH4I did not work at all. For entries 8 and
9, NBS afforded in only 20%, and NCS resulted in no reaction. Thus,
NIS and I2 would work as Iþ sources,19,20 and the Iþ performs
electrophilic attack to a triple bond of ynamide. Although the NIS
might generate a molecular I2 in situ, there would be difference
between I2 and NIS in the efficacy of each Iþ, that is, NIS is a better
source of Iþ than neat and bulk I2. Actually, the experiments at
entries 3e5 gave dark brown solution and multi spots on TLC
monitoring, which imply that the I2 induce many unknown side-
products.
a
a
structural resemblance between
composed of -diketone moiety, anticipates the expansion of the
possibilities and importance of unexplored -keto-imide.
Herein we report a transition metal-free synthesis of
imides from ynamides. The combination of NIS, and DMSO, and
atmospheric air was useful for one-step construction of -keto-
a-keto-imide and benzil, which is
a
a
a-keto-
a
imides skeleton from ynamide substrates. The reaction proceeds
within 1 h at 0 ꢀC, giving moderate yields. The method was also
applicable to the double oxidation of diarylalkynes. Our synthetic
protocol does not require pesky metals and scary oxidants, which is
advantageous as compared to the conventional heavy metal and
sensitive-, and expensive-oxidant approaches. Thus, the protocol
provides contribution to an alternative oxidation method and
greener reaction process.
Table 2
Halogen sources for the formation of a-keto-imides
2. Results and discussion
First, we evaluated the outcome of the NIS/DMSO-controlled
oxidation of the ynamide 1 by varying two elements, solvent and
temperature (Table 1). The larger amount of DMSO as a solvent than
as a stoichiometric reagent is prone to be not generally accepted,
particularly by process chemists, because DMSO and its resultant
dimethyl sulfide have malodorous nature.15 This oxidation was
observed as an exothermic reaction,16 and so the reaction tem-
perature was initially conducted at 0 ꢀC. Treatment of 1 with
1.2 equiv of NIS and 2.8 equiv of DMSO for 1 h in cyclopentyl methyl
ether (CPME) provided the desired 2 in 83% yield, consuming all of
the starting material 1 (entry 1). Although various solvents, such as
THF17 (entry 2), DMSO (entry 3), DMF (entry 4), acetone (entry 5),
2-propanol (entry 6), and toluene (entry 7) were applicable for the
present transformation, the most effective solvent in terms of the
yield was found to be CPME at entry 1. Presumably the tolerance to
acidity inherent in CPME is effective in yielding 2 under the current
NIS/DMSO system. When the reactions under CPME solvent were
performed at room temperature (entry 8) and ꢁ20 ꢀC (entry 9), the
yields decreased in 61% and <33%, respectively. Through all entries,
generation of succinimides was confirmed in the crude products.
Entry
Iodine sources
Yield%
Recovered 1, %
1
2
3
4
5
6
7b
8
9
NIS (1.2 equiv)
NIS (0.6 equiv)
83
63
49
31
72
25
<22
20
Trace
0
14
5
0
0
0
0
5
I
I
2 (1.2 equiv)
2 (1.0 equiv)a
NIS (1.2 equiv), I2 (1.2 equiv)
NIS (1.2 equiv), KI (1.2 equiv)
NIS (1.2 equiv), NH4I (1.2 equiv)
NBS (1.2 equiv)
NCS (1.2 equiv)
w100
a
The reaction was performed under DMSO solvent at 150 ꢀC for 1 h.
Many unknown byproducts were observed on TLC and NMR analyses.
b
Table 3 illustrates different sulfoxide patterns tested. While the
comparable yields between DMSO (entries 1 and 2), diphenyl
sulfoxide (entry 3), and methyl phenyl sulfoxide (entry 4) were
observed, longer alkyl-chained dibutyl sulfoxide (entry 5) and
didodecyl sulfoxide (entry 6) lowered yields, and dimethyl sulfite
(entry 7) gave the miserable yields. For entry 8, no use of sulfoxide
afforded any target 2. For entry 9, addition of diphenyl sulfide21
instead of sulfoxide didn’t work at all. Noteworthy is that all
through entries 1e7 the starting 1 disappeared in appreciably
shorter time: the reactions would end up in only 5 min on TLC
monitoring. In addition, the NMR spectra in the crude states
showed unknown byproduct peaks even in entries 1e4, and the
terrible messy peaks appeared in the entries 5e7, that is, the NIS/
sulfoxide system proves to be rather reactive toward ynamide
substrates, and among them DMSO happens to be a most oppor-
tune reagent for the substrate.
Table 1
Screening of conditionsa
Entry
Solvent
Temp/ꢀC
Yield%
1
2
3
4
5
6
7
8
9c
CPMEb
THF
DMSO
0
0
0
0
0
0
0
rt
ꢁ20
83
51
74
63
68
39
58
61
<33
As shown in Scheme 1, the oxidation of 1 (0.5 mmol) employing
diphenyl sulfoxide (1.4 mmol) gave 0.64 mmol of diphenylsulfane. If
the sulfoxide would work as an oxygen source, the resultant amount
of diphenylsulfane should be 0.76 mmol, that is, twice of the keto-
DMF
Acetone
2-Propanol
Toluene
CPMEb
CPMEb
imide
2 (0.38 mmol): however, the observed amount was
0.64 mmol, that is, 84% of stoichiometric 0.76 mmol. Is the oxygen
atom in atmospheric air involved in this reaction system? Then, the
effect of atmosphere on the oxidation was examined, and the results
were summarized in Table 4. For entry 1, to our surprise, an argon
atmosphere didn’t enable to control the reaction at all, and the crude
a
Reactions were performed under atmospheric air.
Cyclopentyl methyl ether.
b
c
CPME (10 mL) was needed for dissolving 1.

3990
T. Chikugo et al. / Tetrahedron 70 (2014) 3988e3993
Table 3
Table 4
Sulfoxide-mediated formation of
a
-keto-imides
Effect of atmosphere on the oxidation
Entry
Sulfoxides
Yield%
Entry
Atmosphere
Ara
Atmospheric air
O2
Yield%
0b,c
83
1
2
3
4
5
6
7
8
9
DMSO
83
67
75
77
DMSOa
1
2
3
Diphenyl sulfoxide
Methyl phenyl sulfoxide
Dibutyl sulfoxide
Didodecyl sulfoxide
Dimethyl sulfite
dd
85
62
a
Balloon was used.
<44b
Tracec
0
b
Multi spots on TLC and terribly messy spectrum were observed in the crude
state.
c
The reproducibility was confirmed.
de
0
a
DMSO (1.4 equiv) was used, and 7% of 1 remained.
Messy spectrum in the crude state.
The starting 1 was disappeared on TLC.
Without any sulfoxide.
b
c
d
e
Diphenyl sulfide was added instead of the sulfoxide.
was terribly complicated with unidentified byproducts. For entries 2
and 3, an oxygen atmosphere did not improve the yield that an at-
mospheric air furnished. These revealed that the reaction system
needs a certain quantity of gaseous oxygen, and impelled us to add
an antioxidant on this oxidation reaction (Scheme 2). In the presence
of 2,6-di-tert-butyl-4-methyl phenol, the oxidation under atmo-
spheric air was found to occur in 80% yield, which was nearly
comparable yield to entry 2 in Table 4. Considering the antioxidant
effect of 2,6-di-tert-butyl-4-methyl phenol, the mechanism of our
oxidation system would be similar in radical processes of Matsu-
moto’s report.19 Actually, as shown in Scheme 3, an attempt to oxi-
Scheme 2. The oxidation in the presence of 2,6-di-tert-butyl-4-methyl phenol.
dize ynamide 1 under Matsumoto’s condition provided a-keto-imide
Scheme 3. Oxidation of 1 under Matsumoto’s condition.
2 in acceptable 32% yield. Furthermore, indeed, the reaction condi-
tions employing I2 at entries 3 and 4 in Table 2, which yielded 49%
and 31%, are close to Matsumoto’s radical protocol. Thus, the nec-
essary O2 in atmospheric air might be somewhat involved and take
a critical part of the present oxidation system.
corresponding 1,2-diketones are created.25e28 Compared to ynamide
inTable 5, the oxidation required higher reaction temperature (100 ꢀC)
and prolonged reaction time (overnight stirring). For entries 1e3,
diphenyl acetylenewas oxidized to give10 in 70%, and no reactionwas
ensured in the absence of NIS or DMSO. For entries 4 and 5, the 3-
methoxy 11 was obtained in 73% yield, although the sterically hin-
dered 2-methoxy 12 around the triple bond resulted in only 10% yield.
For entries 6e8, the phenol 13, and naphtyl 14, and 3-chlorophenyl 15
were provided in acceptable yield with complete consumption of the
starting alkynes. For entry 9,4-(phenylethynyl)benzonitrile had the
reaction time lengthened to 30 h, and barely reached to 56% yield of 16
along with 22% of unreacted starting alkyne.29
The mechanism in this oxidation is not yet fully known; how-
ever, some points of reaction process would be estimated as
a working hypothesis, which was depicted in Fig. 1 on the basis of
the reaction in Scheme 1. Initially, NIS works as an Iþ source to
activate ynamide 1, providing oxysulfonium 17. The intermediate
1726 could then undergo an addition of molecular oxygen, O2, to
form peroxide 18 and thiyl radical cation. The radical cation could
receive one electron from succinimide anion to bring the diphenyl
sulfide. Finally, the intermediate 18 is engaged by the resultant
succinimide radical to create 19, which can access to the desired 2.
Every step in the route includes quite labile species, and this ex-
plains the oxidation was observed as a fast but an unregulated re-
action. Presumably, argon atmosphere did not enable to advance
from 17 to 18, and the labile 17 totally decomposed to give com-
plicated crude products (Table 4, entry 1).
Scheme 1. A byproduct of diphenylsulfane.
The carbonecarbon triple bonds of various ynamides were con-
verted to the corresponding diketones 3e9 (Table 5), giving mod-
erate and acceptable yields.22,23 The starting ynamides were totally
and quickly consumed through entries; however, several spots on
1
TLC monitoring and unidentified peaks on H NMR were observed,
and so the loss of the yields necessarily accompanied the oxidations.
For Evans auxiliary 4, the reaction at gram-scale successfully pro-
ceeded to afford 1.23 g in 70% yields. The methyl carbamate 3, and N-
methyl tosylamide 5 were isolated in moderate 54% and 65% yields,
respectively. The nitrile 6, methoxy 7, and cyclohexyl 8 required la-
borious purification with column chromatography, yet each was
given in 65%, 48%, and 41% yield. The 2-substituted indole 9 was
barely isolable24 although the 3-substituted indoles with acetyl and
methyl ester didn’t undergo the oxidation cleanly.
The reaction system also proved to be applicable to symmetrical
and unsymmetrical diarylalkynes14 (Table 6), where the

T. Chikugo et al. / Tetrahedron 70 (2014) 3988e3993
3991
Table 5
Substrate scope
Fig. 1. Plausible reaction path to 2 via 17, 18, and 19.
3. Conclusion
In conclusion, we have developed a transition metal-free ap-
proach for double oxidation of ynamide triple bonds as a synthetic
method to prepare a-keto-imide. The reaction employs the quite
conventional reagents of NIS and DMSO as oxidants, and quickly
proceeds under atmospheric air within 1 h at 0 ꢀC. The molecular
oxygen is indispensable, and would play crucial role as a radical
source. The radical based oxidation would get ahead by way of
oxysulfonium intermediate and peroxide species, resulting in in-
stallation of two oxygen units. The method also proved to be ap-
plicable to diarylalkynes for preparation of 1,2-diketones. The
process is still prototype protocol, yet this avoids the use of ex-
pensive, moisture-sensitive, and explosive additives, which make it
potentially greener than current alternatives. Application and
mechanistic elucidation are ongoing for further development of the
related reactions and will be reported in due course.
4. Experimental section
4.1. General
All reactions sensitive to air or moisture were carried out under
an argon atmosphere and anhydrous conditions unless otherwise
noted. Dry solvents were purchased and used without further pu-
rification and dehydration. All reagents were purchased and used
without further purification. Column chromatography was carried
out with silica gel. HRMS were reported on the basis of TOF (time of
flight)-MS, and EB (double-focusing)-MS. Mass spectra were re-
ported on the basis of FAB-MS. 1H and 13C NMR spectra were
recorded with a 5 mm QNP probe at 400 MHz and 100 MHz, re-
spectively. Chemical shifts are reported in d (parts per million) with
reference to residual solvent signals [1H NMR: CHCl3 (7.26); 13C
NMR: CDCl3 (77.0)]. Signal patterns are indicated as s, singlet; d,
doublet; t, triplet; q, quartet; m, multiplet; br, broad.
Table 6
Oxidation of diarylalkynes for preparation of 1,2-diketones
Entry
R
Products
Time/
h
Yield
%
Recovered
alkyne/%
1
Phenyl
Phenyl
Phenyl
3-MeOPh
2-MeOPh
4-OHPh
1-
Naphtyl
3-ClPh
4-CNPh
10
10
10
11
12
13
14
26
12
12
21
21
15
11
70
0
0
73
10
46
81
0
>99
>99
7
16
0
4.2. General procedure for the oxidation
2a
3b
4
For preparation of N-benzyl-2-oxo-2-phenyl-N-tosylacetamide
2 (Table 1, entry 1): to a solution of 1 (181 mg, 0.5 mmol) in CPME
(1.4 mL) and DMSO (0.1 mL, 1.4 mmol) at 0 ꢀC was added NIS
(135 mg, 0.6 mmol) in 1 mL of acetonitrile drop-wise over 5 min.
After stirring for 1 h at 0 ꢀC, the reaction was quenched with 8 mL of
saturated aqueous Na2S2O3, and the mixture was transferred into
a separatory funnel. The aqueous phase was extracted with ethyl
acetate (10 mLꢂ3), and the combined organic phases were washed
5
6
7
0
8
9
15
16
11
30
68
56
0
22
a
Without NIS.
Without DMSO.
b

3992
T. Chikugo et al. / Tetrahedron 70 (2014) 3988e3993
with brine (10 mL), and dried over Na2SO4, and concentrated in
vacuo to give a crude product of 241 mg as brown viscous materials.
Purification by column chromatography (eluent; hexane/
dichloromethane¼1/1) afforded 164 mg of 2 in 83% yield as yellow
viscous materials. Analytical data are identical to the previously
reported.9a 1H NMR (400 MHz, CDCl3) 7.89 (d, J¼7.4 Hz, 2H), 7.75 (d,
J¼8.4 Hz, 2H), 7.65e7.61 (m, 1H), 7.50 (dd, J¼7.4, 7.4 Hz, 2H),
7.27e7.22 (m, 7H), 4.99 (s, 2H), 2.42 (s, 3H) ppm; 13C NMR
(100 MHz, CDCl3) 185.0, 167.8, 145.9, 134.9, 134.72, 134.70, 133.1,
130.1, 129,9, 129.1, 128.75, 128.73, 128.3, 128.1, 48.5, 21.9 ppm.
1057 cmꢁ1; Anal. Calcd for C16H19NO4: C, 66.42; H, 6.62; N, 4.84.
Found: C, 66.13; H, 6.57; N, 4.84.
4.2.7. Ethyl 1-(2-oxo-2-phenylacetyl)-1H-indole-2-carboxylate
(9). Yield 34%, pale green viscous materials; 1H NMR (400 MHz,
CDCl3) 8.38 (d, J¼8.4 Hz, 1H), 8.16 (d, J¼8.4 Hz, 2H), 7.70e7.66 (m,
2H), 7.58e7.51 (m, 3H), 7.44 (s, 1H), 7.38 (t, J¼8.4 Hz, 2H), 4.14 (q,
J¼7.16 Hz, 2H), 1.23 (t, J¼7.16 Hz, 3H) ppm; 13C NMR (100 MHz,
CDCl3) 185.5, 165.6, 161.9, 139.0, 134.5, 133.6, 130.9, 129.9, 128.9,
128.9, 128.3, 125.2, 123.0, 118.7, 116.3, 62.1, 14.4 ppm; MS (EI) m/z:
321 (Mþ); IR (neat): 3058, 2979, 1680, 1445, 1336, 1203, 1173 cmꢁ1
HRMS (DI) calcd for C19H15NO4: 321.1001, found 321.1016.
;
4.2.1. Methyl (2-oxo-2-phenylacetyl)(phenyl)carbamate (3). Yield
54%, colorless viscous materials; 1H NMR (400 MHz, CDCl3) 7.98 (d,
J¼7.3 Hz, 2H), 7.66 (t, J¼7.3 Hz, 1H), 7.57e7.46 (m, 5H), 7.34e7.31 (m,
2H), 3.71 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) 187.7, 169.7, 154.5,
135.2, 134.5, 133.0, 129.8, 129.5 (two peaks are overlapped), 129.2,
128.5, 54.8 ppm; FAB-MS m/z: 283 (Mþ); IR (neat): 3064, 2958, 1739,
1681, 1439, 1281, 1243, 1094 cmꢁ1; Anal. Calcd for C16H13NO4: C,
67.84; H, 4.63; N, 4.94. Found: C, 67.85; H, 4.63; N, 4.80.
4.2.8. 1-Methoxy-3-(phenylethynyl)benzene (10).10 Yield 70%; yel-
low solid materials; 1H NMR (400 MHz, CDCl3) 7.98 (d, J¼8.4 Hz,
4H), 7.67 (t, J¼5.7 Hz, 2H), 7.52 (dd, J¼8.4, 5.7 Hz, 4H) ppm; 13C NMR
(100 MHz, CDCl3) 194.9, 135.2, 133.3, 130.2, 129.3 ppm.
4.2.9. 1-(3-Methoxyphenyl)-2-phenylethane-1,2-dione (11).10 Yield
73%; yellow solid materials; 1H NMR (400 MHz, CDCl3) 7.98 (d,
J¼7.1 Hz, 2H), 7.68e7.64 (m,1H), 7.55e7.47 (m,1H), 7.40 (t, J¼7.8 Hz,
2H), 7.22e7.19 (m, 2H), 3.87 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3)
194.80, 194.78, 160.4, 135.2, 134.5, 133.3, 130.4, 130.2, 129.3, 123.5,
122.2, 113.2, 55.8 ppm.
4.2.2. (S)-1-(2-Oxo-4-phenyloxazolidin-3-yl)-2-phenylethane-1,2-
dione (4). Yield 70%, pale yellow solid; 1H NMR (400 MHz, CDCl3)
7.78 (d, J¼7.2 Hz, 2H), 7.63 (t, J¼7.4 Hz, 1H), 7.50e7.41 (m, 7H), 5.54
(dd, J¼8.7, 4.0 Hz, 1H), 4.89 (dd, J¼8.7, 8.7 Hz, 1H), 4.45 (dd, J¼8.7,
4.0 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3) 187.9, 166.3, 153.7,
137.8, 135.1, 132.7, 129.8, 129.6, 129.5, 129.3, 126.4, 72.3, 57.0 ppm;
FAB-MS m/z: 296 ([MH]þ); IR (neat): 1795, 1705, 1596, 1389, 1336,
1224 cmꢁ1; Anal. Calcd for C17H13NO4: C, 69.15; H, 4.44; N, 4.74.
Found: C, 69.41; H, 4.59; N, 4.74.
4.2.10. 1-(2-Methoxyphenyl)-2-phenylethane-1,2-dione
(12).10 Yield 10%; yellow solid materials; 1H NMR (400 MHz,
CDCl3) 8.03 (dd, J¼7.8, 1.8 Hz, 1H), 7.94 (d, J¼7.8 Hz, 2H), 7.64e7.58
(m, 2H), 7.50 (dd, J¼8.0, 7.8 Hz, 2H), 7.14 (t, J¼8.0 Hz, 1H), 6.94 (d,
J¼8.4 Hz, 1H), 3.57 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) 195.0,
193.8, 160.8, 136.8, 134.1, 133.3, 130.9, 129.7, 129.0, 124.2, 121.9,
112.7, 56.0 ppm.
4.2.3. N-Methyl-2-oxo-2-phenyl-N-tosylacetamide (5). Yield 65%,
white solid; 1H NMR (400 MHz, CDCl3) 7.95 (d, J¼7.4 Hz, 2H), 7.89 (t,
J¼8.4 Hz, 2H), 7.65 (t, J¼7.4 Hz, 1H), 7.54 (dd, J¼7.4, 7.4 Hz, 2H), 7.40
(d, J¼8.4 Hz, 2H), 3.25 (s, 3H), 2.47 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3) 188.3, 167.6, 146.2, 134.8, 133.7, 133.1, 130.4, 130.0, 129.2,
128.7, 31.0, 22.0 ppm; MS (EI) m/z: 317 (Mþ); IR (neat): 1672, 1597,
1450, 1368, 1162, 948 cmꢁ1; Anal. Calcd for C17H13NO4: C, 60.55; H,
4.76; N, 4.41. Found: C, 60.56; H, 4.80; N, 4.29.
4.2.11. 1-(4-Hydroxyphenyl)-2-phenylethane-1,2-dione (13).10 Yield
46%; yellow solid materials; 1H NMR (400 MHz, CDCl3) 7.94 (d,
J¼8.4 Hz, 2H), 7.85 (d, J¼8.8 Hz, 2H), 7.65 (t, J¼7.5 Hz, 1H), 7.50 (dd,
J¼8.4, 7.5 Hz, 2H), 7.06 (br s, 1H), 6.89 (d, J¼8.4 Hz, 2H) ppm; 13C
NMR (100 MHz, CDCl3) 195.8, 194.1, 162.7, 135.5, 133.24, 133.18,
130.3, 129.4, 126.0, 116.5 ppm.
4.2.4. N-Benzyl-2-(4-cyanophenyl)-2-oxo-N-tosylacetamide
(6). Yield 65%, white solid; 1H NMR (400 MHz, CDCl3) 7.97 (d,
J¼8.1 Hz, 2H), 7.80 (d, J¼8.1 Hz, 2H), 7.72 (d, J¼8.4 Hz, 2H),
7.28e7.21 (m, 7H), 4.80 (s, 2H), 2.43 (s, 3H) ppm; 13C NMR
(100 MHz, CDCl3) 186.4,167.0,146.3,136.3,134.5,134.3,132.9,130.2,
130.1, 128.9, 128.7, 128.3, 123.2, 118.0, 117.7, 48.6, 22.0 ppm; FAB-MS
m/z: 419 ([MH]þ); IR (neat): 2233, 1697, 1661, 1363, 1202,
1160 cmꢁ1; Anal. Calcd for C23H18NO4S: C, 66.01; H, 4.34; N, 6.69.
Found: C, 65.70; H, 4.49; N, 6.57.
4.2.12. 1-(Naphthalen-1-yl)-2-phenylethane-1,2-dione (14).12 Yield
81%; yellow solid materials; 1H NMR (400 MHz, CDCl3) 9.33 (d,
J¼8.2 Hz, 1H), 8.11 (d, J¼8.2 Hz, 1H), 8.04 (d, J¼7.2 Hz, 2H), 7.93 (dd,
J¼8.4, 7.2 Hz, 2H), 7.75 (t, J¼8.4 Hz, 1H), 7.67e7.61 (m, 2H),
7.53e7.45 (m, 3H) ppm; 13C NMR (100 MHz, CDCl3) 197.5, 194.9,
136.3, 135.4, 135.0, 134.4, 133.6, 131.2, 130.3, 129.7, 129.3, 129.1,
128.9, 127.4, 126.2, 124.7 ppm.
4.2.13. 1-(Naphthalen-1-yl)-2-phenylethane-1,2-dione (15).10 Yield
68%; yellow oil; 1H NMR (400 MHz, CDCl3) 7.98e7.96 (m, 3H), 7.84
(d, J¼7.8 Hz, 1H), 7.70e7.62 (m, 2H), 7.55e7.44 (m, 3H) ppm; 13C
NMR (100 MHz, CDCl3) 193.9, 193.3, 135.7, 135.5, 135.1, 134.8, 133.0,
130.7, 130.3, 129.9, 129.4, 128.4 ppm.
4.2.5. Methyl (2-(4-methoxyphenyl)-2-oxoacetyl)(phenyl)carbamate
(7). Yield 48%, whitish green solid; 1H NMR (400 MHz, CDCl3) 7.94
(d, J¼9.0 Hz, 2H), 7.54e7.44 (m, 3H), 7.32e7.30 (m, 2H), 7.02 (d,
J¼9.0 Hz, 2H), 3.90 (s, 3H), 3.70 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3) 186.7, 169.9, 164.8, 154.5, 135.5, 132.0, 129.8, 129.5, 128.6,
126.0, 114.7, 56.0, 54.8 ppm; FAB-MS m/z: 313 ([MH]þ); IR (neat):
2958, 2844, 1740, 1670, 1596, 1285, 1245, 1162, 1092 cmꢁ1; Anal.
Calcd for C17H15NO5: C, 65.17; H, 4.83; N, 4.47. Found: C, 65.44; H,
4.90; N, 4.40.
4.2.14. 4-(2-Oxo-2-phenylacetyl)benzonitrile (16).10 Yield 56%; yel-
low solid materials; 1H NMR (400 MHz, CDCl3) 8.10 (d, J¼8.7 Hz,
2H), 7.98 (d, J¼8.4 Hz, 2H), 7.82 (d, J¼8.7 Hz, 2H), 7.71 (t, J¼7.4 Hz,
1H), 7.75 (dd, J¼8.4, 7.4 Hz, 2H) ppm; 13C NMR (100 MHz, CDCl3)
193.3, 192.7, 136.1, 135.7, 133.0, 132.7, 130.5, 130.3, 129.5, 118.1,
117.8 ppm.
4.2.6. Methyl (2-cyclohexyl-2-oxoacetyl)(phenyl)carbamate (8). Yield
41%, white solid; 1H NMR (400 MHz, CDCl3) 7.49e7.41 (m, 3H), 7.20
(dd, J¼8.1, 1.7 Hz, 2H), 3.77 (s, 3H), 2.80e2.73 (m, 1H), 2.15e2.11 (m,
2H), 1.87e1.84 (m, 2H), 1.73e1.70 (m, 1H), 1.57e1.48 (m, 2H),
1.38e1.23 (m, 3H) ppm; 13C NMR (100 MHz, CDCl3) 200.6, 170.3,
154.8, 135.2, 129.7, 129.4, 128.5, 54.8, 47.5, 28.1, 26.1, 25.9 ppm; FAB-
MS m/z: 290 ([MH]þ); IR (neat): 1740, 1692, 1492, 1440, 1283,
Acknowledgements
We are pleased to thank Dr. Toshiyuki Iwai at OMTRI for assis-
tance with HRMS. We are very grateful to Professor Michael P.
Schramm at CSULB for helpful discussion.

T. Chikugo et al. / Tetrahedron 70 (2014) 3988e3993
3993
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Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.04.080.
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