Metal-Free Iodine-Catalyzed Oxidation of Ynamides and Diaryl Acetylenes into 1,2-Diketo Compounds

Article abstract of DOI:10.1021/acs.joc.8b00484

Metal-free oxidation of ynamides is described, employing pyridine-N-oxides as oxidants under molecular iodine catalysis. In stark contrast to Br?nsted acid catalysis, iodophilic activation of ynamides diverts the reaction manifold into a dioxygenation pathway. This oxidation is very rapid at room temperature with only 2.5 mol % I₂. Furthermore, this protocol could be extended to nonactivated alkynes, such as diarylacetylenes, to deliver various benzil derivatives.

Full text of DOI:10.1021/acs.joc.8b00484

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Metal-Free Iodine-Catalyzed Oxidation of Ynamides
and Diaryl Acetylenes into 1,2-Diketo Compounds
Seung Woo Kim, Tae-woong Um, and Seunghoon Shin
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00484 • Publication Date (Web): 01 Apr 2018
Downloaded from http://pubs.acs.org on April 1, 2018
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Page 1 of 26
The Journal of Organic Chemistry
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MetalꢀFree IodineꢀCatalyzed Oxidation of Ynamides
and Diaryl Acetylenes into 1,2ꢀDiketo Compounds
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Seung Woo Kim, TaeꢀWoong Um, and Seunghoon Shin*
Department of Chemistry, Center for New Directions in Organic Synthesis (CNOS) and Research
Institute for Natural Sciences, Hanyang University, 222ꢀWangsimniꢀro, Seongdongꢀgu, Seoul 04763,
Korea, sshin@hanyang.ac.kr
ABSTRACT Metalꢀfree oxidation of ynamides is described, employing pyridineꢀNꢀoxides as oxidants
under molecular iodine catalysis. In stark contrast to Brønsted acid catalysis, iodophilic activation of
ynamides diverts the reaction manifold into a dioxygenation pathway. This oxidation is very rapid at
room temperature with only 2.5 mol% of I2. Furthermore, this protocol could be extended to nonꢀ
activated alkynes, such as diarylacetylenes, to deliver various benzil derivatives.
KEYWORDS iodine catalysis; 1,2ꢀdiketo compound; pyridineꢀNꢀoxide; alkyne oxidation; halogen
bonding.
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INTRODUCTION
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Molecular iodine, being inexpensive and easy to handle, has been widely used in organic synthesis.1
Besides stoichiometric iodofunctionalizations that incorporate an iodine atom in the product, a wide
variety of iodineꢀcatalyzed transformations have been developed as promising alternatives to the metal
catalysis, including dehydration, condensation, conjugate addition, esterification, acetalization and
glycosylation.2 However, some of these transformations are suspected to involve trace amount of HI
formed inꢀsitu as the true catalyst.3 In principle, I2 interacts with Lewis basic heteroatoms through
halogen bonding induced by the positive polarization (σꢀhole).4 Considering the softness of such
bonding, the activation by I2 could be extended to CꢀC πꢀbonds in an analogous fashion to electrophilic
metal catalysis5 and indeed iodofunctionalizations of alkynes have provided versatile synthetic
methods.6 However, alkyne activation that is catalytic in I2 is surprisingly rare,7 presumably due to the
highly endergonic IꢀY (Y= Lewis base) bond formation during the catalyst turnover (for example, BDE
(IꢀI) = 36 kcal/mol). In the course of our recent investigation on the Brønsted acidꢀcatalyzed oxidation
of ynamides (Scheme 1A),8 we thus initiated a study directed toward I2ꢀcatalyzed activation of alkynes.
Catalytic oxidation by iodous species have typically employed superꢀstoichiometric end oxidants,
such as H2O2,9a TBHP,9b mCPBA,9c DMSO,9d chloramines,9e and hypochlorite.9f These oxidants
generate catalytically active iodine species with higher oxidation states, such as hypoiodites (IOꢀ) and
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ꢀ
iodites (IO2 ), reminiscent of innerꢀsphere oxidation in transition metal catalysis. However, use of less
reactive oxidants, such as pyridineꢀNꢀoxides or DMSO, have required transition metal10,11 or Brønsted
acid catalysis.12 Furthermore, the mechanism of molecular iodine catalysis is not understood well and
some of the iodoniumꢀmediated reactions were proposed to involve radical mechanisms.13 Herein, we
report an I2ꢀ or IPy2BF4/2HBF4ꢀcatalyzed oxidation of ynamides and diaryl alkynes into αꢀketoamides
and benzil derivatives, respectively. This metalꢀfree protocol obviates the use of toxic or expensive
transition metal catalysts, and provides an efficient route to 1,2ꢀdiketo compounds.14
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RESULTS AND DISCUSSION
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Comparison of Brønsted acid vs. Iodophilic Activation.
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-
R2
NTf2
NH
O
HNTf2 (cat.)
indole
O
our previous
report (ref. 8a)
Pyr
H
R2N
(R1 = NR2)
R1
R2
(-pyr)
path A
R2
NR2
I
1 or 3
+
pyridine-
N-oxide
I-Y
(-pyr)
R2
pyridine-
N-oxide
(-pyr)
path B
O
Y-
R2
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Y-
Pyr
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I-Y (cat.)
R2
O
O
R1
(Y = I or pyr+)
Pyr
I
O
R1
R1
O
II
III
2 or 4
Scheme 1. Iodineꢀcatalyzed oxidation of alkynes with pyridineꢀNꢀoxides
Table 1. PyridineꢀNꢀoxideꢀmediated oxidation of ynamide 1aa
entry
1
conditions
2a (%)b
5a (%)b
HNTf2 (10 mol%), NꢀMeꢀindole (3 equiv), 2 h
0
5aꢀH, 70
I2 (100 mol%), NꢀMeꢀindole (3 equiv), 30min
I2 (2.5 mol%), 10 min
HI (10 mol%),c NꢀMeꢀindole (3 equiv), 80 oC, 3 h
HI (10 mol%),c 1 h
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0
5aꢀH, 22
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5a-H, 34
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0d
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HNTf2 (10 mol%), 6 h
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a[1a] = 0.5 M in DCE (1,2ꢀdichloroethane). Yields after chromatography. Hydriodic acid was
b
c
generated in situ from nBu4NI and TfOH. dUnreacted 1a was recovered.
Initially, we set out to examine the feasibility of I2 to activate ynamide 1a in a similar manner to our
previous HNTf2ꢀcatalyzed oxidative coupling protocol (path A, Scheme 1). While the oxidative
coupling of 1a with NꢀMeꢀindole in the presence of 10 mol% of HNTf2 delivered indole adduct 5aꢀH
uneventfully as in our previous report (entry 1, Table 1),8a a similar reaction with I2 (1.0 equiv.) gave a
messy mixture from which the desired adduct 5a-I could not be observed and instead 5aꢀH (22 %) and
unexpected ketoamide 2a (14 %) were identified (entry 2). Presumably, the formation of 5aꢀH could be
due to action of HI generated from the reaction of I2 and NꢀMeꢀindole. Surprisingly, use of a catalytic
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amount of I2 (2.5 mol%) gave ketoamide 2a in 86 % yield with remarkable efficiency (entry 3).
Considering the similarity of the postulated intermediates I and II (Scheme 1) except the presence of
iodine at C2 and the counterꢀanion, this sharp change of chemoselectivity (path A vs. B) depending on
the activator was remarkable. We interpreted that iodoꢀadduct II, formed from 1a and I2, was
preferentially attacked by another molecule of 2ꢀClꢀpyridineꢀNꢀoxide instead of indole nucleophile into
III. Subsequent attack of Iꢀ would deliver αꢀketoamide 2a via a Kornblumꢀtype oxidation, liberating I2
for the next catalytic cycle.15
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We next checked whether the formation of 2a can be catalyzed by Brønsted acid. The reaction with
HI as a catalyst in the presence of NꢀMeꢀindole did not proceed at RT, but upon heating, only indole
adduct 5aꢀH could be isolated, albeit with much less efficiency than HNTf2 (entries 4 vs. 1).
Surprisingly, with HI as a catalyst in the absence of an indole nucleophile, a highly efficient formation
of ketoamide 2a was still observed (entry 5). In this case, a facile oxidation of HI by 2ꢀClꢀpyridineꢀNꢀ
oxide generated I2 which then catalyzed oxidation into 2a, because we confirmed that treating 2ꢀClꢀ
pyridineꢀNꢀoxide with 2 equiv. of HI immediately generated 2ꢀClꢀpyridine, presumably in a reversible
manner (Eq. 1).16 Therefore, the formation of 2a is most likely from the action of I2, not HI. This was
corroborated by the observation that redoxꢀinactive Brønsted acid, HNTf2, failed to produce 2a (entry 6).
These experiments suggested that protioꢀintermediate I formed reversibly in the mixture in entries 1, 2,
4 and 6, but could not be oxidized into 2a, in contrast to the iodoꢀintermediate II.
The Scope of Ynamide Oxidation.
Encouraged by the efficiency of this Nꢀoxide mediated oxidation of ynamides, we examined the scope
of this iodine catalysis (Scheme 2). Ynamides having various Nꢀsulfonyl groups (Ms, pꢀTs, and oꢀNs)
were excellent substrates in the current conditions (2a-d). NꢀAlkyl, allyl, aryl as well as benzyl groups
were well accommodated with excellent chemoselectivity. Generally, electronꢀrich Ar group led to a
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faster and more selective oxidation than electronꢀpoor Ar substrates (2k-m vs. 2n). Sterically hindered
aryl group (2m) or heteroaryl group (2p) did not have any deleterious effect. However, the reaction of a
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carbamate substrate led to a poorer result even with higher I2 loading (40 mol%) and at 80 C (2j).
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Unfortunately, replacing Ar group with alkyl (nꢀhexyl) or CO2Et or terminal ynamides led to no
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Scheme 2. Scope of iodine catalyzed oxidation of ynamides 1a
a1 (0.2 mmol) in DCE (0.5 M); Yields after chromatography; abbreviations: PMP (pꢀMeOꢀC6H4), Ns
b
o
(2ꢀnitrobenzenesulfonyl). The reaction was conducted at 80 C for 19 h in the presence of 40 mol% of
I2. c20 mol% of I2 was used (RT, 4 h).
Examination of Conditions for Diaryl Acetylenes.
Next, we turned our attention to extending the ynamide oxidation into unactivated alkynes such as
diphenylacetylene. However, the reaction 3a with 5 mol% of I2 did not proceed at RT and the
o
conversion of 3a required heating (80 C) and extended reaction time (72 h) (entries 1ꢀ2, Table 2). In
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terms of solvent, the reaction was substantially accelerated in CH3CN, with a complete conversion being
observed in 24 h (entries 3ꢀ6). Increasing the amount of I2 (20 mol%) led to 95 % of 3a in 13 h at 80 oC
(entry 7). Notably, the iodonium sources had a profound effect on the reaction (entries 8ꢀ11). Among
them, ICl (5 mol%) and Barluenga reagent IPy2BF4 (5 mol%) stood out in promoting this oxidation.
Gratifyingly, the catalytic activity of IPy2BF4 was further boosted with 10 mol% of HBF4 as a coꢀ
catalyst,7c delivering 4a even at RT in 4 hours (entries 12ꢀ13). Most likely, HBF4 help dissociate the
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+
pyridinium from IPy2 , generating coordinatively unsaturated IPy+ which activates alkynes as a true
catalyst. Other oxidants were also examined along with I2 (20 mol%): the reaction with mCPBA and
tBuOOH as oxidants gave the product in 90 % and 16 % yield, respectively, although the reaction took a
longer time and was slightly messier (entries 14ꢀ15). However, all other oxidants, including H2O2,
oxone, Ph3P=O, trimethylamineꢀNꢀoxide, DMSO and O2, did not produce 4a.
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Table 2. 2ꢀClꢀPyridineꢀNꢀoxideꢀmediated oxidation of diphenylacetylene 3a
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entry
1
Catalyst (mol %)
conditions
RT, 72 h
Solvent
DCE
4a (%)a,b
trace
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I2 (5)
2
I2 (5)
I2 (5)
80 oC, 60 h
80 oC, 72 h
80 oC, 72 h
80 oC, 72 h
80 oC, 24 h
80 oC, 13 h
80 oC, 7 h
80 oC, 6 h
80 oC, 4 h
80 oC, 6 h
80 oC, 10 min
RT, 4 h
DCE
83 %
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DMSO
Dioxane
DMF
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I2 (5)
80 %
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I2 (5)
81 %
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I2 (5)
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
84 %
7
I2 (20)
(95 %)
(70 %)
(86 %)
(97 %)
(76 %)
(96 %)
(95 %)
90 %
8
IBr (5)
9
ICl (5)
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14c
15d
ICl (10)
IPy2BF4 (5)
IPy2BF4 (5)+HBF4 (10)
IPy2BF4 (5)+HBF4 (10)
I2 (20)
80 oC, 13 h
80 oC, 48 h
I2 (20)
16 %
aDetermined by GC with 1,2ꢀdiethyl phthalate as an internal reference; isolated yields in parenthesis.
bThe remaining mass balance was unreacted starting 3a. cmCPBA was used instead of 2ꢀClꢀpyrꢀNꢀoxide.
dtꢀBuOOH (5.5 M in nꢀdecane) was used instead of 2ꢀClꢀpyrꢀNꢀoxide.
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The Scope of Diaryl Acetylene Oxidation.
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We set out to examine the scope of unactivated alkynes employing three different catalytic systems,
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i.e. condition A: 5 mol% of IPy2BF4/2HBF4 at RT; condition B: 10 mol% of ICl at 80 C; condition C:
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20 mol% of I2 at 80 C (Scheme 3). IPy2BF4/2HBF4 (5 mol%, condition A) performed well with 3a-d
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and those bearing electronꢀwithdrawing groups, such as 3e-g, delivering respective products (4a-g) at
room temperature in good yields. However, substrates bearing electronꢀrich aryl ring (3h and 3l) and
Lewis basic atoms, such as free phenol, aniline and acid (3i-k), failed with IPy2BF4/2HBF4, presumably
because of facile deactivation of the catalyst. In these cases, ICl (10 mol%, condition B) produced
respective products smoothly (4h-l). Presence of Lewis basic atoms in ketone (3m), ester (3n) and
pyridyl rings (3o-p) as well as orthoꢀsubstituents (3q-r) seemed to interfere with both IPy2BF4/2HBF4
or ICl catalyst systems. In these cases (3m-r), I2 (20 mol%, condition C) was found to be the most
robust and resistant to deactivation, although it took higher catalyst loading and longer time than
conditions A and B. Surprisingly, substrate 3s bearing styryl group also delivered 4s with ICl, albeit
lower yield. Unfortunately, however, phenylacetylene readily decomposed and 1ꢀphenylꢀ1ꢀheptyne as
well as 1,4ꢀdiphenylꢀ1,3ꢀdiynes was unreactive under conditions A~C.
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Scheme 3. Scope of 2ꢀClꢀpyridineꢀNꢀoxideꢀmediated oxidation of diarylacetylenesa
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a3 (0.2 mmol) in CH3CN (0.5 M); Condition A: IPy2BF4 (5 mol%)/HBF4 (10 mol%), RT, 2~5 h;
Condition B: ICl (10 %), 80 C, 6~12 h; Condition C: I2 (20 %), 80 C, 12~36 h; Yields after
chromatography.
o
o
Mechanistic Discussion
In order to shed light on the mechanism of this iodonium catalysis, we obtained time profile for the
conversions of 1a and 3a using different iodonium sources (Figure 1). The reaction of 1a was followed
by GC with 1 mol% of iodonium loadings. Typically, the reaction proceeded very fast initially (<5 min),
and this is followed by a mild plateau in the conversion. The observed conversion was in the order of I2
>> IPy2BF4 > ICl > IBr (Figure 1a). The order of reactivity was significantly changed in nonꢀpolarized
alkyne 3a: ICl > IPy2BF4 > IBr >> I2 (10 mol% loading, Figure 1b). For ynamide 1a, use of IPy2BF4 (1
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mol%) along with HBF4 coꢀcatalyst (2 mol%) did not make any difference in the conversion. In sharp
contrast, the reaction of diphenylacetylene 3a was dramatically improved with the use of coꢀcatalyst
HBF4, allowing a fast reaction even at RT: with 5 mol% of IPy2BF4 and 10 mol% of HBF4 at RT, >90 %
conversion into 4a was achieved in 2 h.17
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(a)
(b)
Figure 1. Time course for the oxidation of 1a and 3a by using gas chromatography: (a) Conversion of
1a in the presence of 1 mol% of iodonium sources in DCE (RT); (b) Conversion of 3a in the presence of
10 mol% of iodonium sources in CH3CN (80oC).
Evaluation of various iodonium salts in Figure 1(a) indicated I2 had the fastest conversion among I2,
IBr and ICl, which suggested the strongest nucleophile Iꢀ (as Yꢀ in III, Scheme 1) presumably led to the
fastest conversion. Therefore, in the reaction of electronꢀrich alkynes such as ynamide 1a, our data are
consistent with a rateꢀlimiting catalyst turnover step (III to 2a). We also considered the possible
involvement of 2ꢀClꢀpyridine, liberated from 2ꢀClꢀpyridineꢀNꢀoxide, acting in the catalyst turnover step
as nucleophile Yꢀ (in III) to generate I(2ꢀClꢀPy)+ as an active catalyst. However, as in Figure 1(a), the
conversion with IPy2BF4 (with or without HBF4 coꢀcatalyst) was much slower than that with I2 and
furthermore, less basic 2ꢀClꢀpyridine would be less likely to participate as a nucleophile than pyridine in
the catalyst turnover.18 In addition, we attempted to generate putative I(2ꢀClꢀPy)+ by mixing I2, 2ꢀClꢀ
pyridine and AgBF4 in 1:1:3 ratio19 in an effort to quantify the conversion due to I(2ꢀClꢀPy)+. The
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filtrate of this mixture was tested as a potential catalyst (2.5 mol% loading, Eq. 2): in this experiment,
only 25 % of 2a was obtained after a longer time (2 h), suggesting that 1 mol% of I2 is a superior
catalyst to 2.5 mol% of “I(2ꢀClꢀPy)+”. This suggest that involvement of 2ꢀClꢀpyridine in the catalyst
turnover step is much less likely.
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In the case of nonꢀactivated alkynes, such as diphenylacetylene 3a, a more polarized ICl performs the
o
best overall oxidation among I2, ICl and IBr at 80 C (Figure 1(b)). In addition, the observed rateꢀ
enhancement with the coꢀcatalytic system (i.e. IPy2BF4/2HBF4 vs. IPy2BF4 alone) was much more
dramatic than ynamide 1a. This suggests that polarization of iodonium species is critical with 3a and is
consistent with rateꢀdetermining activation of the alkyne 3a to form II (Scheme 1). Based on the
different overall efficiency depending on the iodonium sources (Figure 1(b)), catalyst turnover in the
reaction 3a may also be achieved through the attack of Yꢀ on III (Yꢀ = Clꢀ, Pyr, Brꢀ or Iꢀ, respectively for
ICl, IPyr2BF4, IBr and I2).20 Finally, the oxidation of 1a was not affected when run in the presence of
radical inhibitors (2,6ꢀdiꢀtBuꢀphenol) and the oxidation of 1a performed inside Arꢀatmosphere glove box
proceeded in an essentially the same manner. These experiments excluded the possible involvement of
radical species or oxygenꢀdependent pathways.13
CONCLUSION
In conclusion, we presented herein a novel molecular iodineꢀcatalyzed oxidation of alkynes, using
pyridineꢀNꢀoxides as terminal oxidants. Ynamides can be efficiently oxidized into αꢀketoamides with
only 2.5 mol% of I2 and diaryl alkynes can also be oxidized into benzil derivatives with IPy2BF4/2HBF4,
ICl, or I2. This nonꢀmetal oxidation by pyridineꢀNꢀoxides was proposed to follow a closed shell
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mechanism, with iodonium species function as πꢀactivators5 and the catalyst turnover is achieved
through IꢀY (Y = respective Lewis bases in IꢀY reagents) bond formation.
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Experimental Section
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General Information: All materials were obtained from commercial suppliers and were used without
1
further purification. H, protonꢀdecoupled 13C{1H}, and 19F NMR spectra were recorded on a Bruker
(400 MHz) spectrometer with TMS as an internal standard. Gas chromatographic analysis was
conducted on Agilent Technology 7890B GC system with nꢀdodecane or oꢀdiethyl phthalate as internal
standards. LCMS analysis was conducted on Agilent 6150 Quadrupole LC/MS with ESI or APCI
ionization sources. High resolution mass spectra (HRMS) were obtained from Korea Basic Science
Institute (KBSI, Daegu) on a magnetic sectorꢀelectric sector double focusing mass analyzer.
Representative formation of ketoamides 2a from ynamides 1a: Ynamide 1a (41.9 mg, 0.2 mmol) and
2ꢀchloroꢀpyridine Nꢀoxide (77.7 mg, 0.6 mmol) was dissolved in 1,2ꢀdichloroethane (0.4 ml) in a 4 ml
screwꢀcapped vial. Iodine (1.3 mg, 2.5 mol%) as a stock solution was added and the reaction mixture
was stirred at RT for 30 min. The residue was directed loaded onto SiO2 column and was purified by
flash chromatography (EtOAc:nHex = 1:10~1:4).
Representative formation of benzil 4a from diarylacetylene 3a: Diphenylacetylene (35.6 mg, 0.2
mmol) and 2ꢀchloroꢀpyridine Nꢀoxide (77.7mg, 0.6mmol) was dissolved in CH3CN (0.4 ml) in a 4 ml
screwꢀcapped vial. To this was added IPy2BF4 (3.7 mg, 5 mol%) and HBF4·etherate (4.7mg, 10 mol%)
in a freshly made, premixed stock solution and the mixture was stirred at RT for the indicated time. The
residue was directed loaded onto SiO2 column and was purified by flash chromatography (EtOAc:nHex
= 1:10~1:4).
NꢀMethylꢀNꢀ(methanesulfonyl)ꢀ2ꢀoxoꢀ2ꢀphenylacetamide (2a).10b yellow solid (91%, 44.0 mg); mp
76ꢀ77 oC; 1H NMR (400 MHz, CDCl3): δ 7.91 (d, J = 7.8 Hz, 2H), 7.64 (t, J = 7.2 Hz, 1H), 7.51 (t, J =
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7.5 Hz, 2H), 3.38 (s, 3H), 3.28 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 188.5, 167.2, 134.8, 132.3,
130.0, 128.9, 40.8, 31.3; HRMS (FAB) Calcd for C10H12NO4S+ [M+H]+ 242.0482; found 242.0484.
NꢀBenzylꢀNꢀ(methanesulfonyl)ꢀ2ꢀoxoꢀ2ꢀphenylacetamide (2b).10d yellow sticky oil (94%, 59.5 mg); 1H
NMR (400 MHz, CDCl3): δ 7.90 (d, J = 7.1 Hz, 2H), 7.63 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.9 Hz, 2H),
7.45ꢀ7.35 (m, 5H), 5.16 (s, 2H), 2.90 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 188.5, 167.2, 134.80,
134.78, 132.3, 130.0, 129.1, 128.9, 128.7, 128.6, 47.5, 43.1; HRMS (FAB) Calcd for C16H16NO4S+
[M+H]+ 318.0795; found 318.0798.
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NꢀBenzylꢀNꢀ((2ꢀnitrophenyl)sulfonyl)ꢀ2ꢀoxoꢀ2ꢀphenylacetamide (2c). yellow solid (85%, 72.0 mg);
mp 90ꢀ92 oC ; 1H NMR (400 MHz, CDCl3): δ 8.31ꢀ8.14 (m, 1H), 7.79ꢀ7.66 (m, 5H), 7.57 (t, J = 7.4 Hz,
13
1H), 7.40 (t, J = 7.6 Hz, 2H), 7.32 (d, J = 7.0 Hz, 2H), 7.23ꢀ7.17 (m, 3H), 5.16 (s, 2H); C{1H} NMR
(100 MHz, CDCl3): δ 187.3, 166.9, 148.3, 135.1, 134.9, 134.8, 132.3, 132.1, 131.7, 129.8, 128.8, 128.7,
128.6, 128.2, 124.7, 49.9; HRMS (FAB) Calcd for C21H17N2O6S+ [M+H]+ 425.0802; found 425.0804.
o
1
NꢀBenzylꢀ2ꢀoxoꢀ2ꢀphenylꢀNꢀtosylacetamide (2d).13b white solid (95%, 75.7 mg); mp 89ꢀ91 C; H
NMR (400 MHz, CDCl3): δ 7.88 (d, J = 8.6 Hz, 2H), 7.75 (d, J = 8.4 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H),
7.49 (t, J = 7.9 Hz, 2H), 7.26ꢀ7.22 (m, 7H), 4.98 (s, 2H), 2.40 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3): δ 187.8, 167.6, 145.6, 134.7, 134.5, 134.4, 132.9, 129.8, 129.7, 129.3, 128.7, 128.5, 128.1,
127.8, 48.3, 21.7; HRMS (FAB) Calcd for C22H20NO4S+ [M+H]+ 394.1108; found 394.1109.
2ꢀOxoꢀN,2ꢀdiphenylꢀNꢀtosylacetamide (2e).10f yellow solid (78%, 58.9 mg); mp 152ꢀ154 oC; 1H NMR
(400 MHz, CDCl3): δ 7.93 (d, J = 7.3 Hz, 2H), 7.75 (d, J = 8.3 Hz, 2H), 7.65 (t, J = 7.4 Hz, H), 7.52 (t,
13
J = 7.9 Hz, 2H), 7.33ꢀ7.45 (m, 5H), 7.13 (d, J = 7.3 Hz, 2H), 2.48 (s, 3H); C{1H} NMR (100 MHz,
CDCl3): δ 187.6, 166.7, 146.0, 134.7, 134.1, 133.5, 132.7, 130.6, 130.2, 129.8, 129.6, 129.5, 129.1,
129.0, 21.8; HRMS (FAB) Calcd for C21H18NO4S+ [M+H]+ 380.0951; found 380.0952.
o
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NꢀMethylꢀ2ꢀoxoꢀ2ꢀphenylꢀNꢀtosylacetamide (2f).10f white solid (96%, 61.0 mg); mp 113ꢀ114 C; H
NMR (400 MHz, CDCl3): δ 7.94 (d, J = 7.1 Hz, 2H), 7.89 (d, J = 8.4 Hz, 2H), 7.64 (t, J = 7.4 Hz, 1H),
13
7.53 (t, J = 7.9 Hz, 2H), 7.39 (d, J = 8.1 Hz, 2H), 3.24 (s, 3H), 2.46 (s, 3H); C{1H} NMR (100 MHz,
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CDCl3): δ 188.1, 167.3, 145.9, 134.5, 133.5, 132.8, 130.2, 129.7, 128.9, 128.4, 30.7, 21.7; HRMS
(FAB) Calcd for C16H16NO4S+ [M+H]+ 318.0795; found 318.0797.
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NꢀAllylꢀ2ꢀoxoꢀ2ꢀphenylꢀNꢀtosylacetamide (2g).10f pale yellow oil (92%, 63.1 mg); H NMR (400
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MHz, CDCl3): δ 7.94ꢀ7.89 (m, 4H), 7.66 (t, J = 7.4 Hz, 1H), 7.53 (t, J = 7.9 Hz, 2H), 7.38 (d, J = 8.1
Hz, 2H), 5.75 (ddt, J = 17.1, 10.2, 6.0 Hz, 1H), 5.25 (dd, J = 17.2, 1.1 Hz, 1H), 5.16 (dd, J = 10.2, 1.1
Hz, 1H), 4.35 (d, J = 5.9 Hz, 2H), 2.46 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 187.8, 167.0,
145.8, 134.5, 134.4, 132.8, 130.7, 130.0, 129.7, 128.9, 128.6, 119.5, 47.3, 21.8; HRMS (FAB) Calcd for
C18H18NO4S+ [M+H]+ 344.0951; found 344.0953.
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NꢀDodecylꢀ2ꢀoxoꢀ2ꢀphenylꢀNꢀtosylacetamide (2h). white sticky oil (99%, 62.6 mg); H NMR (400
MHz, CDCl3): δ 7.94ꢀ7.90 (m, 4H), 7.63 (t, J = 7.4 Hz, 1H), 7.52 (t, J = 7.8 Hz, 2H), 7.38 (d, J = 8.1
Hz, 2H), 3.64 (t, J = 7.8 Hz, 2H), 2.45 (s, 3H), 1.66ꢀ1.61 (m, 2H), 1.32ꢀ1.26 (m, 18H), 0.88 (t, J = 7.0
13
Hz, 3H); C{1H} NMR (100 MHz, CDCl3): δ 187.9, 167.3, 145.7, 134.5, 134.4, 133.0, 130.1, 129.7,
128.9, 128.4, 45.8, 31.9, 29.6, 29.5, 29.45, 29.37, 29.0, 28.2, 26.8, 22.7, 21.7, 14.1; HRMS (FAB) Calcd
for C27H38NO4S+ [M+H]+ 472.2516; found 472.2518.
o
NꢀCyclohexylꢀ2ꢀoxoꢀ2ꢀphenylꢀNꢀtosylacetamide (2i). white solid (93%, 71.61 mg); mp 124ꢀ126 C ;
1H NMR (400 MHz, CDCl3): δ 7.94 (d, J = 8.2 Hz, 4H), 7.62 (t, J = 7.4 Hz, 1H), 7.52 (t, J = 7.4 Hz,
2H), 7.38 (d, J = 8.1 Hz, 2H), 3.78 (tt, J = 12.2, 3.6 Hz, 1H), 2.46 (s, 3H), 2.38ꢀ2.21 (m, 2H), 1.87ꢀ1.72
(m, 2H), 1.72ꢀ1.50 (m, 2H), 1.26ꢀ1.17 (m, 4H); 13C{1H} NMR (100 MHz, CDCl3): δ 186.8, 167.9,
145.5, 134.9, 134.1, 133.0, 130.1, 129.7, 128.8, 128.3, 61.0, 29.1, 26.4, 24.9, 21.8; HRMS (FAB) Calcd
for C21H24NO4S+ [M+H]+ 386.1421, found 386.1423.
1
1ꢀ(2ꢀOxooxazolidinꢀ3ꢀyl)ꢀ2ꢀphenylethaneꢀ1,2ꢀdione (2j).10f brown oil (37%, 16.2 mg); H NMR (400
MHz, CDCl3): δ 7.89 (d, J = 7.0 Hz, 2H), 7.65 (tt, J = 7.4, 1.2 Hz, 1H), 7.52 (t, J = 7.9 Hz, 2H), 4.60 (t,
J = 7.7 Hz, 2H), 4.17 (t, J = 8.3 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3): δ 187.8, 166.5, 153.1,
+
134.8, 132.4, 129.4, 129.1, 64.0, 41.0; HRMS (FAB) Calcd for C11H10NO4 [M+H]+ 220.0604, found
220.0607.
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o
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NꢀBenzylꢀ2ꢀoxoꢀ2ꢀ(pꢀtolyl)ꢀNꢀtosylacetamide (2k). yellow solid (96%, 78.8 mg); mp 120ꢀ122 C ; H
1
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NMR (400 MHz, CDCl3): δ 7.76 (t, J = 8.7 Hz, 4H), 7.21ꢀ7.30 (m, 9H), 4.97 (s, 2H), 2.41 (s, 3H), 2.39
(s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 187.5, 167.7, 145.7, 145.6, 134.8, 134.6, 130.5, 129.8,
129.6, 129.1, 128.52, 128.49, 128.1, 127.8, 48.3, 21.9, 21.7; HRMS (FAB) Calcd for C23H22NO4S+
[M+H]+ 408.1264, found 408.1265.
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NꢀBenzylꢀ2ꢀ(4ꢀmethoxyphenyl)ꢀ2ꢀoxoꢀNꢀtosylacetamide (2l). yellow solid (97%, 76.0 mg); mp 152ꢀ
155 oC ; 1H NMR (400 MHz, CDCl3): δ 7.84 (d, J = 8.7 Hz, 2H), 7.76 (d, J = 6.1 Hz, 2H), 7.26ꢀ7.21 (m,
7H), 6.95 (d, J = 8.7 Hz, 2H), 4.97 (s, 2H), 3.85 (s, 3H), 2.38 (s, 3H); 13C{1H} NMR (100 MHz,
CDCl3): δ 186.6, 167.7, 164.7, 145.5, 134.9, 134.6, 132.1, 129.8, 128.54, 128.49, 128.0, 127.8, 125.9,
114.3, 55.6, 48.3, 21.7; HRMS (FAB) Calcd for C23H22NO5S+ [M+H]+ 424.1213, found 424.1216.
o
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NꢀBenzylꢀ2ꢀmesitylꢀ2ꢀoxoꢀNꢀtosylacetamide (2m). white solid (82%, 72.2 mg); mp 59ꢀ60 C ; H
NMR (400 MHz, CDCl3): δ 7.85 (d, J = 8.4 Hz, 2H), 7.26ꢀ7.18 (m, 7H), 6.88 (s, 2H), 4.99 (s, 2H), 2.44
(s, 6H), 2.39 (s, 3H), 2.28 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 188.9, 167.6, 145.4, 143.3,
140.1, 135.1, 134.7, 130.8, 129.6, 129.5, 128.9, 128.34, 128.32, 127.7, 48.9, 22.0, 21.7, 21.3; HRMS
(FAB) Calcd for C25H26NO4S+ [M+H]+ 436.1577, found 436.1579.
NꢀBenzylꢀ2ꢀoxoꢀNꢀtosylꢀ2ꢀ(4ꢀ(trifluoromethyl)phenyl)acetamide (2n). white solid (64%, 59.0 mg); mp
140ꢀ142 oC; 1H NMR (400 MHz, CDCl3): δ 7.99 (d, J = 8.1 Hz, 2H), 7.78ꢀ7.72 (m, 4H), 7.27ꢀ7.24 (m,
13
7H), 4.99 (s, 2H), 2.42 (s, 3H); C{1H} NMR (100 MHz, CDCl3): δ 186.5, 167.0, 145.9, 135.9, 135.4
(q, J = 32.7, 65.4 Hz), 134.4, 134.2, 129.92, 129.90, 128.6, 128.5, 128.1, 128.0, 125.9 (q, J = 3.7, 3.5
Hz), 123.4 (q, J = 271.5, 271.5 Hz), 48.3, 21.7; 19F NMR (376 MHz, CDCl3): δ ꢀ63.3 HRMS (FAB)
Calcd for C23H19F3NO4S+ [M+H]+ 462.0981, found 462.0984.
NꢀBenzylꢀ2ꢀ(4ꢀbromophenyl)ꢀ2ꢀoxoꢀNꢀtosylacetamide (2o). yellow solid (93%, 88.0 mg); mp 120ꢀ121
oC; 1H NMR (400 MHz, CDCl3): δ 7.74ꢀ7.72 (m, 4H), 7.63 (d, J = 8.7 Hz, 2H), 7.25ꢀ7.22 (m, 7H), 4.97
(s, 2H), 2.39 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 186.8, 167.2, 145.8, 134.5, 134.4, 132.3,
131.7, 131.0, 129.9, 128.55, 128.48, 128.1, 127.9, 48.3, 21.7; HRMS (FAB) Calcd for C22H19BrNO4S+
[M+H]+ 472.0213, found 472.0216.
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NꢀMethylꢀ2ꢀoxoꢀ2ꢀ(thiophenꢀ3ꢀyl)ꢀNꢀtosylacetamide (2p). pale yellow solid (97%, 62.7 mg); mp 96ꢀ
98 oC; 1H NMR (400 MHz, CDCl3): δ 8.14 (dd, J = 2.8, 1.0 Hz, 1H), 7.91 (d, J = 8.3 Hz, 2H), 7.60 (dd,
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J = 5.1, 1.0 Hz, 2H), 7.42ꢀ7.39 (m, 3H), 3.23 (s, 3H), 2.47 (s, 3H); C{1H} NMR (100 MHz, CDCl3):
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7
8
δ181.6, 167.0, 146.0, 137.8, 135.7, 133.6, 130.1, 128.4, 127.2, 127.0, 30.9, 21.7; HRMS (FAB) Calcd
9
+
for C14H14NO4S2 [M+H]+ 324.0359; found 324.0356.
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o
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Benzil (4a).11b pale yellow solid (96%, 40.3 mg); mp 95ꢀ96 C; H NMR (400 MHz, CDCl3): δ 7.98
(dd, J = 8.1, 1.0 Hz, 4H), 7.66 (tt, J = 7.4, 1.2 Hz, 2H), 7.53 (d, J = 7.9 Hz, 4H), C{1H} NMR (100
13
MHz, CDCl3): δ 194.6, 134.9, 133.0, 129.9, 129.0; HRMS (FAB) Calcd for C14H11O2 [M+H]+
+
211.0754, found 211.0756.
1ꢀ(4ꢀMethoxyphenyl)ꢀ2ꢀphenylethaneꢀ1,2ꢀdione (4b).11b yellow sticky oil (80%, 38.4 mg); H NMR
1
(400 MHz, CDCl3): δ 7.98ꢀ7.92 (m, 4H), 7.64 (tt, J = 7.4, 1.7 Hz, 1H), 7.49 (t, J = 7.5 Hz, 2H), 6.97 (d,
J = 9.0 Hz, 2H), 3.87 (s, 3H); C{1H} NMR (100 MHz, CDCl3): δ 194.9, 193.2, 165.0, 134.8, 133.2,
13
132.4, 129.9, 129.0, 126.1, 114.4, 55.7; HRMS (FAB) Calcd for C15H13O3 [M+H]+ 241.0859, found
+
241.0862.
1ꢀPhenylꢀ2ꢀ(pꢀtolyl)ethaneꢀ1,2ꢀdione (4c).11b yellow sticky oil (88%, 39.5 mg); H NMR (400 MHz,
1
CDCl3): δ 7.96 (dd, J = 8.2, 1.0 Hz, 2H), 7.86(d, J = 8.3 Hz, 2H), 7.63 (tt, J = 1.2, 7.4 Hz, 1H), 7.49 (t, J
= 8.0 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 2.42 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 194.8, 194.4,
146.3, 134.8, 133.1, 130.6, 130.0, 129.9, 129.8, 129.0, 22.0; HRMS (FAB) Calcd for C15H13O2 [M+H]+
+
225.0910, found 225.0912.
1ꢀ(Naphthalenꢀ1ꢀyl)ꢀ2ꢀphenylethaneꢀ1,2ꢀdione (4d). yellow solid (88%, 45.8 mg); mp 101ꢀ102 C; 1H
o
NMR (400 MHz, CDCl3): δ 9.30 (d, J = 8.6 Hz, 1H), 8.09 (d, J = 8.2 Hz, 1H), 8.02 (d, J = 7.1 Hz, 2H),
7.91 (t, J = 8.0 Hz, 2H), 7.73 (t, J = 7.7 Hz, 1H), 7.65ꢀ7.58 (m, 2H), 7.51ꢀ7.44 (m, 3H); C{1H} NMR
13
(100 MHz, CDCl3): δ 197.2, 194.6, 136.0, 135.1, 134.8, 134.1, 133.4, 131.0, 130.0, 129.5, 129.1, 128.9,
128.6, 127.2, 126.0, 124.5; HRMS (FAB) Calcd for C18H13O2 [M+H]+ 261.0910, found 261.0912.
+
1ꢀ(4ꢀNitrophenyl)ꢀ2ꢀphenylethaneꢀ1,2ꢀdione (4e).11c yellow solid (92%, 46.9 mg); mp 140ꢀ143 C; 1H
o
NMR (400 MHz, CDCl3): δ 8.35 (d, J = 9.0 Hz, 2H), 8.17 (d, J = 9.0 Hz, 2H), 8.00ꢀ7.98 (m, 2H), 7.71
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(tt, J = 7.5, 1.3 Hz, 1H), 7.55 (t, J = 8.2 Hz, 2H); C{1H} NMR (100 MHz, CDCl3): δ 192.9, 192.1,
13
1
2
3
+
151.2, 137.3, 135.5, 132.4, 131.0, 130.1, 129.3, 124.1; HRMS (FAB) Calcd for C14H10NO4 [M+H]+
4
5
256.0604, found 256.0606.
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o
1ꢀ(3ꢀchlorophenyl)ꢀ2ꢀphenylethaneꢀ1,2ꢀdione (4f).11c pale yellow solid (96%, 47.0 mg); mp 90ꢀ92 C;
9
1H NMR (400 MHz, CDCl3): δ 7.98ꢀ7.96 (m, 3H), 7.84 (dt, J = 7.8, 1.2 Hz, 1H), 7.71ꢀ7.65 (m, 1H),
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7.63 (ddd, J = 8.0, 2.1, 1.0 Hz, 1H), 7.53 (t, J = 8.1 Hz, 2H), 7.46 (t, J = 7.9 Hz, 1H); C{1H} NMR
(100 MHz, CDCl3): δ 193.6, 193.0, 135.5, 135.2, 134.8, 134.5, 132.7, 130.4, 130.0, 129.6, 129.1, 128.1;
+
HRMS (FAB) Calcd for C14H10ClO2 [M+H]+ 245.0364, found 245.0366.
1ꢀ(4ꢀChlorophenyl)ꢀ2ꢀphenylethaneꢀ1,2ꢀdione (4g).11b yellow solid (87%, 42.6 mg); mp 76ꢀ77 C; H
NMR (400 MHz, CDCl3): δ 7.96 (d, J = 7.1 Hz, 2H), 7.92 (d, J = 8.7 Hz, 2H), 7.70ꢀ7.63 (m, 2H), 7.51
(t, J = 8.1 Hz, 2H), 7.48 (d, J = 8.7 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3): δ 194.0, 193.2, 141.7,
o
1
135.2, 132.9, 131.5, 131.3, 130.0, 129.6, 129.2; HRMS (FAB) Calcd for C14H10ClO2 [M+H]+
+
245.0364, found 245.0367.
1,2ꢀBis(4ꢀmethoxyphenyl)ethaneꢀ1,2ꢀdione (4h).11b yellow solid (92 %, 49.7 mg); mp 60ꢀ62 C; H
o
1
NMR (400 MHz, CDCl3): δ 7.94 (d, J = 9.0 Hz, 4H), 6.96 (d, J = 9.0 Hz, 4H), 3.87 (s, 6H); C{1H}
13
+
NMR (100 MHz, CDCl3): δ 193.5, 164.9, 132.4, 126.3, 114.3, 55.6; HRMS (FAB) Calcd for C16H15O4
[M+H]+ 271.0965, found 271.0967.
1ꢀ(4ꢀHydroxyphenyl)ꢀ2ꢀphenylethaneꢀ1,2ꢀdione (4i).11c pale yellow solid (78%, 35.3 mg); mp 128ꢀ129
oC; 1H NMR (400 MHz, CDCl3): δ 7.97ꢀ7.95 (m, 2H), 7.87 (d, J = 8.8 Hz, 2H), 7.65 (tt, J = 7.4, 1.2 Hz,
1H), 7.50 (t, J = 8.0 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3): δ 195.3,
+
193.5, 162.2, 135.0, 133.0, 132.8, 130.0, 129.1, 125.9, 116.1; HRMS (FAB) Calcd for C14H11O3
[M+H]+ 227.0703, found 227.0706.
o
1
1ꢀ(4ꢀAminophenyl)ꢀ2ꢀphenylethaneꢀ1,2ꢀdione (4j). yellow solid (72%, 32.4 mg); mp 123ꢀ125 C; H
NMR (400 MHz, CDCl3): δ 7.96 (d, J = 7.3 Hz, 2H), 7.76 (3, J = 8.5 Hz, 2H), 7.62 (t, J = 7.5 Hz, 1H),
7.48 (t, J = 7.8 Hz, 2H), 6.62 (d, J = 8.4 Hz, 2H); C{1H} NMR (100 MHz, CDCl3): δ 195.6, 192.8,
13
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153.1, 134.6, 133.4, 132.7, 129.9, 128.9, 123.1, 114.0; HRMS (FAB) Calcd for C14H12NO2 [M+H]+
226.0863, found 226.0865.
+
1
2
3
4
5
6
7
8
9
o
1
4ꢀ(2ꢀOxoꢀ2ꢀphenylacetyl)benzoic acid (4k). pale yellow solid (89%, 45.2 mg); mp 219ꢀ221 C; H
NMR (400 MHz, acetoneꢀd6): δ 8.24 (d, J = 8.7 Hz, 2H), 8.11 (d, J = 8.7 Hz, 2H), 8.01(dd, J = 8.4, 1.2
Hz, 2H), 7.80 (tt, J = 7.4, 1.3 Hz, 1H), 7.64 (t, J = 8.2 Hz, 2H); 13C{1H} NMR (100 MHz, acetoneꢀd6): δ
195.01, 194.97, 166.6, 137.0, 136.8, 133.6, 131.1, 130.59, 130.58, 130.2; HRMS (FAB) Calcd for
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+
C15H11O4 [M+H]+ 255.0652, found 255.0655.
1ꢀPhenylꢀ2ꢀ(thiophenꢀ2ꢀyl)ethaneꢀ1,2ꢀdione (4l).11c yellow sticky oil (92%, 39.7 mg); H NMR (400
1
MHz, CDCl3): δ 8.04ꢀ8.02 (m, 2H), 7.83 (dd, J = 4.9, 1.1 Hz, 1H), 7.79 (dd, J = 3.9, 1.1 Hz, 1H), 7.64
(tt, J = 7.4, 1.2 Hz, 1H), 7.50 (t, J = 7.8 Hz, 2H), 7.17 (dd, J = 4.9, 3.9 Hz, 1H), 7.53ꢀ7.48 (m, 3H);
13C{1H} NMR (100 MHz, CDCl3): δ 192.1, 185.7, 139.9, 137.0, 136.8, 134.9, 132.6, 130.2, 129.0,
128.9; HRMS (FAB) Calcd for C12H9O2S+ [M+H]+ 217.0318, found 217.0320.
1ꢀ(4ꢀAcetylphenyl)ꢀ2ꢀ(4ꢀmethoxyphenyl)ethaneꢀ1,2ꢀdione (4m).11b yellow solid (99 %, 55.9 mg); mp
128ꢀ131oC; 1H NMR (400 MHz, CDCl3): δ 8.10ꢀ8.02 (m, 4H), 7.95 (d, J = 8.9 Hz, 2H), 6.99 (d, J = 8.9
Hz, 2H), 3.90 (s, 3H), 2.65 (s, 3H); C{1H} NMR (100 MHz, CDCl3): δ 197.3, 193.9, 192.3, 165.2,
13
141.2, 136.2, 132.5, 130.1, 128.7, 125.8, 114.5, 55.7, 27.0; HRMS (FAB) Calcd for C17H15O4 [M+H]+
+
283.0965, found 283.0968.
1
Ethyl 4ꢀ(2ꢀoxoꢀ2ꢀphenylacetyl)benzoate (4n). yellow sticky oil (90 %, 50.7 mg); H NMR (400 MHz,
CDCl3): δ 8.17 (d, J = 8.6 Hz, 2H), 8.04 (d, J = 8.6 Hz, 2H), 7.98 (d, J = 7.2 Hz, 2H), 7.68 (t, J = 7.4
Hz, 1H), 7.53 (t, J = 7.7 Hz, 2H), 4.41 (q, J = 7.1 Hz, 2H), 1.41 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (100
MHz, CDCl3): δ 193.8, 193.7, 165.4, 136.0, 135.7, 135.1, 132.7, 130.1, 130.0, 129.8, 129.1, 61.7, 14.3;
HRMS (FAB) Calcd for C17H15O4 [M+H]+ 283.0965, found 283.0968.
+
1
1ꢀPhenylꢀ2ꢀ(pyridinꢀ3ꢀyl)ethaneꢀ1,2ꢀdione (4o). dark purple sticky oil (70%, 29.6mg); H NMR (400
MHz, CDCl3): δ 9.18 (dd, J = 2.1, 0.6 Hz, 1H), 8.88 (dd, J = 4.9, 1.7 Hz, 1H), 8.33 (dt, J = 8.0, 2.1 Hz,
1H), 8.02ꢀ7.99 (m, 2H), 7.70 (tt, J = 5.9, 1.6 Hz, 1H), 7.57ꢀ7.49 (m, 3H); 13C{1H} NMR (100 MHz,
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CDCl3): δ 192.8, 192.5, 154.5, 151.1, 137.2, 135.3, 132.5, 130.1, 129.2, 128.8, 124.0; HRMS (FAB)
Calcd for C13H10NO2 [M+H]+ 212.0706, found 212.0708.
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3
4
5
o
1ꢀPhenylꢀ2ꢀ(pyridinꢀ2ꢀyl)ethaneꢀ1,2ꢀdione (4p). yellow solid (72%, 30.4 mg); mp 72ꢀ73 C; 1H NMR
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7
8
(400 MHz, CDCl3): δ 8.65 (d, J = 4.7 Hz, 1H), 8.20 (d, J = 7.8 Hz, 1H), 7.96ꢀ7.91 (m, 3H), 7.63 (tt, J =
9
7.4, 1.2 Hz, 1H), 7.53ꢀ7.48 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 196.2, 195.2 151.7 149.9,
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+
137.3, 134.7, 133.2, 129.6, 128.9, 128.2, 123.2; HRMS (FAB) Calcd for C13H10NO2 [M+H]+ 212.0706,
found 212.0708.
1ꢀ(2ꢀMethoxyphenyl)ꢀ2ꢀphenylethaneꢀ1,2ꢀdione (4q).11b yellow sticky oil (85%, 40.8 mg); H NMR
1
(400 MHz, CDCl3): δ 8.01 (dd, J = 7.8, 1.7 Hz, 1H), 7.91 (d, J = 8.4 Hz, 2H), 7.62ꢀ7.56 (m, 2H), 7.48 (t,
13
J = 7.9 Hz, 2H), 7.11 (t, J = 7.6 Hz, 1H), 6.92 (d, J = 8.4 Hz, 1H), 3.54 (s, 3H); C{1H} NMR (100
MHz, CDCl3): δ 194.7, 193.6, 160.5, 136.6, 133.8, 132.9, 130.5, 129.3, 128.8, 123.8, 121.6, 112.4, 55.7;
HRMS (FAB) Calcd for C15H13O3 [M+H]+ 241.0859, found 241.0862.
+
o
1ꢀ(2ꢀFluorophenyl)ꢀ2ꢀphenylethaneꢀ1,2ꢀdione (4r). pale yellow solid (85%, 38.8 mg); mp 57ꢀ59 C;
1H NMR (400 MHz, CDCl3): δ 8.05 (td, J = 7.4, 1.8 Hz, 1H), 7.99ꢀ7.96 (m, 2H), 7.68ꢀ7.61 (m, 2H),
7.52 (t, J = 7.5 Hz, 2H), 7.34 (td, J = 7.6, 1.0 Hz, 1H), 7.12 (ddd, J = 10.5, 8.4, 0.9 Hz, 1H); C{1H}
13
NMR (100 MHz, CDCl3): δ 193.1, 191.9, 162.9 (d, J = 256.9 Hz), 136.9 (d, J = 9.0 Hz), 134.7, 132.1
(d, J = 2.0 Hz), 130.8 (d, J = 1.7 Hz), 129.9, 129.0, 125.0 (d, J = 3.3 Hz), 122.4 (d, J = 11.0 Hz), 116.7
(d, J = 21.6 Hz); F NMR (376 MHz, CDCl3): δ ꢀ107.3; HRMS (FAB) Calcd for C14H10FO2 [M+H]+
19
+
229.0659, found 229.0661.
1
(E)ꢀ1,4ꢀDiphenylbutꢀ3ꢀeneꢀ1,2ꢀdione (4s). yellow sticky oil (43%, 19.8 mg); H NMR (400 MHz,
CDCl3): δ 8.04 (d, J = 8.3 Hz, 2H), 7.71 (d, J = 16.4 Hz, 1H), 7.67ꢀ7.59 (m, 3H), 7.52 (t, J = 6.4 Hz,
2H), 7.47ꢀ7.39 (m, 3H), 7.14 (dd, J = 16.4, 1.1 Hz, 1H); C{1H} NMR (100 MHz, CDCl3): δ 193.3,
13
192.8, 148.9, 134.7, 134.0, 132.8, 131.6, 130.2, 131.6, 130.2, 129.1, 128.92, 128.89, 122.4; HRMS
+
(FAB) Calcd for C16H13O2 [M+H]+ 237.0910, found 237.0913.
ACKNOWLEDGMENT
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The authors thank the National Research Foundation of Korea (NRFꢀ2012M3A7B4049653, NRFꢀ
2014ꢀ011165 and NRFꢀ2017R1A2B4010888) for generous financial support.
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SUPPORTING INFORMATION
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Reaction conditions optimization; reaction summary (conditions A~C) for Table 3; details of
mechanistic experiments; copies of 1H and 13C NMR spectra of all new compounds.
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Angew. Chem., Int. Ed. 2014, 53, 8718ꢀ8721. (b) Stopka, T.; Niggemann, M.; Maulide, N. αꢀCarbonyl
Cations in SulfoxideꢀDriven Oxidative Cyclizations. Angew. Chem., Int. Ed. 2017, 56, 13270ꢀ13274. (c)
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Huang, H.; Fan, J.; He, G.; Yang, Z.; Jin, X.; Liu, Q.; Zhu, H. Generation of Oxazolidine 2,4 diones
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Chem. Eur. J. 2016, 22, 2532ꢀ2538. (d) Wan, Z.; Jones, C. D.; Mitchell, D.; Pu, J. Y.; Zhang, T. Y.
Practical Method for Transforming Alkynes into αꢀDiketones. J. Org. Chem. 2005, 71, 826ꢀ828. (e)
Chen, C. Y.; Hu, W.ꢀP.; Yan, P.ꢀC.; Senadi, G. C.; Wang, J.ꢀJ. MetalꢀFree, AcidꢀPromoted Synthesis of
Imidazole Derivatives via a Multicomponent Reaction. Org. Lett. 2013, 15, 6116ꢀ6119. (f) Chen, Z.ꢀS.;
Yang, F.; Ling, H.; Li, M.; Gao, J.ꢀM.; Ji, K. MetalꢀFree, SiteꢀSelective Addition to Ynones: An
Approach to Synthesize Substituted Quinoline Derivatives. Org. Lett. 2016, 18, 5828ꢀ5831 and ref. 8.
For related oxidations using Nꢀoxides oxidants via inꢀsitu generated keteniminium ions: (g) Kaiser, D.;
de la Torre, A.; Shaaban, S.; Maulide, N. MetalꢀFree Formal Oxidative CꢀC Coupling by In Situ
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Kaiser, D.; Maulide, N. Flexible and Chemoselective Oxidation of Amides to αꢀKeto Amides and αꢀ
Hydroxy Amides. J. Am. Chem. Soc. 2017, 139, 6578ꢀ6581. (i) Kaiser, D.; Teskey, C. J.; Adler, P.;
Maulide, N. Chemoselective Intermolecular CrossꢀEnolateꢀType Coupling of Amides. J. Am. Chem.
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13. In some oxidation of ynamides mediated by stoichiometric amount of iodonium sources, radical
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1650ꢀ1654.
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X.; Zhao, J. WackerꢀType Oxidation of Alkynes into 1,2ꢀDiketones Using Molecular Oxygen. Org. Lett.
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16. Experimental details can be found in Supporting Informations.
17. In contrast, the reaction of 3a with ICl (10 mol%) at RT, under otherwise the standard condition,
led to 4a only in ~30 % after 6 h.
18. In addition, the oxidation of 1a under the standard condition was significantly inhibited by 2,2’ꢀ
bipyridyl or 1,10ꢀphenanthroline, but not by 2ꢀClꢀpyridine at all (Figure S4 in Supporting Informations).
Therefore, liberated 2ꢀClꢀpyridine do not deactivate I2 catalyst and the formation of I(2ꢀClꢀPy)+ from I2
and 2ꢀClꢀpyridine as an active catalyst is not likely.
19. For a related synthesis of IPy2BF4: Chalker, J. M.; Thompson, A. L.; Davis, B. G. Org. Synth.
2010, 87, 288ꢀ298. We found that the formation of I(2ꢀClꢀpyridine)+ from this mixture is nearly
quantitative as judged from the gravimetric analysis of AgI (98%) formed (Eq. 2). In a control
experiment, we observed no reaction of 1a with 2ꢀClꢀpyridineꢀNꢀoxide (3 equiv.) and AgBF4 (5 %) as a
catalyst (see Supporting Information), supporting that presence of excess AgBF4 is not responsible for
the conversion of 1a.
20. If 2ꢀClꢀpyridine participates in the catalyst turnover, identical conversions should have been
observed after 10 % conversion in Figure 1(b).
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