One-pot, two-step desymmetrization of symmetrical benzils catalyzed by the methylsulfinyl (dimsyl) anion

Article abstract of DOI:10.1039/c4ob00759j

An operationally simple one-pot, two-step procedure for the desymmetrization of benzils is herein described. This consists in the chemoselective cross-benzoin reaction of symmetrical benzils with aromatic aldehydes catalyzed by the methyl sulfinyl (dimsyl) anion, followed by microwave-assisted oxidation of the resulting benzoylated benzoins with nitrate, avoiding the costly isolation procedure. Both electron-withdrawing and electron-donating substituents may be accommodated on the aromatic rings of the final unsymmetrical benzil. the Partner Organisations 2014.

Full text of DOI:10.1039/c4ob00759j

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Journal Name
RSCPublishing
ARTICLE
One-pot, two-step desymmetrization of symmetrical
benzils catalyzed by the methylsulfinyl (Dimsyl) anion
Cite this: DOI:
10.1039/x0xx00000x
Daniele Ragno, Olga Bortolini,* Pier Paolo Giovannini, Alessandro Massi,*
Salvatore Pacifico, and Anna Zaghi
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
An operationally simple oneꢀpot, twoꢀstep procedure for the desymmetrization of benzyls is
herein described. This consists in the chemoselective crossꢀbenzoin reaction of symmetrical
benzils with aromatic aldehydes catalyzed by the methyl sulfinyl (dimsyl) anion, followed by
microwaveꢀassisted oxidation of the resulting benzoylated benzoins with nitrate, avoiding the
costly isolation procedure. Both electronꢀwithdrawing and electronꢀdonating substituents may
be accommodated on the aromatic rings of the final unsymmetrical benzil.
www.rsc.org/
benzils. While such a strategy is highly effective for the
preparation of symmetrically substituted benzils, its extension
Introduction
to the synthesis of unsymmetrical benzils is complicated by the
lack of regiochemical control in the crossꢀbenzoin reaction of
two different aldehydes.
Unsymmetrical benzils are attractive intermediates in organic
synthesis and structural motifs of considerable importance in
biologically active compounds.1 They represent a direct access
to valuable heterocyclic compounds such as quinoxalines,
pyrazines, imidazoles,1b,2 and exhibit potential as inhibitors of
mammalian carboxylesterases (CE) involved in the metabolism
of esterified drugs including cocaine, heroin, and xenobiotics.3
In addition, they display photoresponsive activity in
photoisomerization processes4 and free radical photoinduced
polymerizations.5 Effective methods for the preparation of
unsymmetrically substituted benzils are based on the oxidation
O
O
Ph
N
Ar
Ar
'
Ar'
Ar
O
h
O
O
i
Ar
Ar'
[O]
[O]
Ar
Ar
'
a
of various precursors as alkynes,6 alkenes,7
methylene aryl ketones,9 benzotriazolyl ketones10 (paths a-e
Scheme 1), on the oxidative coupling of acetophenones with
unactivated arenes (path
),11 on the oxidative CꢀC bond
cleavage of 1,3ꢀdiketones12 (path
), or on nonꢀoxidative
procedures from iminoethanones2a,13 and ꢀketoaldehydes14
α
ꢀhydroxyketones,8
g
O
Ar
X
X
[O]
Ar'
,
[O]
O
Ar
Ar
'
b
+
Ar
H
O
f
Ar
'
f
[O]
O
[O]
g
c
Ar
'
e
[O]
Ar
β
O
d
OH
Ar
'
(paths h-i). Although some of the reported synthetic protocols
are quite effective, the access to the above precursors is not
without associate efficiency consideration as the need of
multiple nonꢀtrivial steps in their synthesis,15 the use of
expensive starting materials, and/or metal catalysts.16
Therefore, a simple, straightforward, and chemoselective
general method to access unsymmetrically substituted benzils is
highly desirable. Such a method should employ commercial or
readily available starting materials, avoid the use of toxic
reagents, and be easily adaptable to the preparation of a
diversified library of benzils. Undoubtedly, the most direct and
atomꢀefficient preparation of benzils is through the benzoin
Ar
O
Bt
Ar
'
Ar
Bt = benzotriazolyl
Scheme 1. Existing synthetic strategies to unsymmetrically substituted benzils
As previously pointed out, two crucial elements exercise
control on the chemoselectivity of the process: the preference
of the dimsyl anion for
the aptitude of the generated acyl anion equivalent III to
intercept the aldehyde (crossꢀcoupling) rather than a second
molecule of (homoꢀcoupling). By this strategy, the
benzoylated benzoin products are obtained with high
αꢀdiketone over aldehyde addition, and
2
1
3
condensation of aromatic aldehydes under cyanide or
Nꢀ
efficiency in a fully atomꢀeconomic manner. Noteworthy, the
heterocyclic carbene (NHC) catalysis to obtain
αꢀ
hydroxyketones,17 which in turn are conveniently oxidized to
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DOI: 10.1039/C4OB00759J
dimsyl anion belongs to the restricted class of organocatalysts benzil 1a in 70% isolated yield (entry 8). Aiming at decreasing
capable of promoting umpolung transformations.17
the reaction time, it was next evaluated the use of microwave
With a ready access to benzoylated benzoins in hand, we (MW) dielectric heating (entries 9ꢀ13).24 With a temperature
envisaged the possibility of a direct elaboration of these control of 150 °C, the complete conversion of 3a was achieved
after 2 hours and benzil 1a could be recovered in gratifying
88% yield (entry 9).
compounds getting back to the
sequence is none other than the desymmetrization of a
symmetrical benzil , with the advantage that the aryl
substituents of the final benzil
αꢀdiketone stage. Overall, the
1
Table 1. Optimization of the oxidation reaction of the benzoylated benzoin
3a.a
4
may be chosen independently.
O
Ar
O
O
Ar
'
O
O
Ar
O
Ar
CH3
O
promoter (2 equiv.)
O
oxidant
H2C
S
Ar
O
O
1
O
3
solvent, temp., time
I
3a
1a
CH3
O
O
Ar
'
O
CH3
S
CH2
Ar
Entry
Prom.
Oxidant
Solv.
Temp.
(°C)
25
25
25
25
70
70
70
125
150
150
150
150
150
Time
Yield
(%)b
28
Ar
CH2
S
O
O
(h)
16
16
16
16
24
24
24
24
2
O
O
1
2
3
4
5
NaOHc
NaOHc
NaH
DBU
DBU
DBU
TFA
ꢀ
aird
aird
aird
aird
aird
DMSO
MeOH
THFe
Ar
Ar
IV
II
41
20
DMSO
EtOAc
EtOAc
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
<5
51
50
22
70
CH3
O
CH2
S
O
O
Ar
'
CHO
f
6
O2
2
aird
Ar
Ar
7
8g
NH4NO3
NH4NO3
NH4NO3
NH4NO3
NH4NO3
NH4NO3
III
9g,h
10g,h
11h,i
12h,j
13h,j,k
ꢀ
ꢀ
ꢀ
88
52
53
95
1. cross-benzoin
2. oxidation
O
1
2
2
2
O
Ar
'
Ar
Ar
'
CHO
+
Ar
Ar
one-pot
desymmetrization
TFA
TFA
2
O
O
92
1
4
c
aReactions performed with 0.50 mmol of 3a. bIsolated yield. 1 N aqueous
Scheme 2. Proposed mechanism for the cross-coupling of symmetrical benzils
I
1
with aromatic aldehydes mediated by the dimsyl anion and the designed two-
solution. dAirꢀfilled balloon. eAnhydrous solvent. fOxygenꢀfilled balloon.
2
step sequence towards unsymmetrical benzils
gNH4NO3: 10 equiv. Microwaveꢀassisted reaction performed with a singleꢀ
h
4
mode cavity dedicated reactor (Biotage Initiator). iNH4NO3: 5 equiv.
jNH4NO3: 3 equiv. kDegassed and performed under argon.
Results and discussion
These conditions represented the better compromise between
reaction time (entry 10) and oxidant loading (entry 11).
Following the observation that a small excess of NH4NO3 (2
equiv.) was sufficient for the oxidation of a genuine sample of
benzoin, benzil formation from benzoylated benzoin 3a was
finally optimized with three equivalents of oxidant in a more
acidic reaction medium (2:1 AcOHꢀTFA), obtaining 1a in 95%
isolated yield (entry 12). The implication of NH4NO3 in 3a
oxidation, either or not in the presence of oxygen, was evident
from an experiment performed under an argon atmosphere
(entry 13). Two major reacting species have been proposed to
form from ammonium nitrate in strong acidic media, that are
The planned strategy towards unsymmetrical benzils
a preliminary study to find out the most suitable conditions for
an efficient benzoylated benzoinꢀtoꢀbenzil conversion via initial
4 required
benzoyl (Bz) group removal from
3 and subsequent in situ
oxidation of the resulting benzoin intermediate. Aerobic basic
conditions were first investigated due to their successful
utilization in the oxidation of genuine benzoins to benzils and
their suitability for the Bz deprotection step.8,20 Hence,
exposure of the model benzoylated benzoin 3a to either
NaOH,20 NaH,8b or DBU,8a in different base/solvent
combinations at different temperatures and in the presence of
air led to a maximum 51% yield of isolated benzil 1a (Table 1,
entries 1ꢀ5; selected experiments). Also, no improvements were
observed by replacing air with pure oxygen as the terminal
oxidant (entry 6).8b,c,20,21 Poor results were obtained under the
above conditions mainly because of the instability of the
intermediate benzoin in basic aqueous media (entries 1ꢀ2)
and/or the only partial hydrolysis of the benzoate functionality
in organic solvents (entries 3ꢀ6). Therefore, aerobic acidic
conditions were next examined by treating 3a with a 2:1 acetic
acid (AcOH)ꢀtrifluoroacetic acid (TFA) mixture at 125 °C
under air. Again, benzil 1a was recovered in modest yield
(22%, entry 7), but a good level of conversion of 3a into
benzoin was observed. This result and literature reports22,23
prompted us to consider the utilization of the ammonium
nitrate/acetic acid couple in virtue of its stronger oxidation
ability. Accordingly, a solution of 3a and NH4NO3 (10 equiv.)
in acetic acid was warmed at 125 °C for 24 hours furnishing
+
nitronium (NO2 ) and nitrosonium (NO+) ions, both active in
the oxidation of alcohols to carbonyl compounds.25 It seems
reasonable, therefore, to predict a mechanism that involves
hydrolysis of the benzoyl group of 3a, followed by addition of
+
NO2 and/or NO+ to form the benzoin nitrate and/or benzoin
nitrite esters, next converted into benzil. The recovery of
equimolar benzoic acid, eventually containing the
corresponding benzamide, further supported this hypothesis.
With the optimal conditions identified, the scope of the
oxidation step was next explored. Accordingly, a set of
benzoylated benzoins
3 (Table 2, entries 1ꢀ8) was initially
prepared through crossꢀbenzoin reactions (anhydrous DMSO,
tꢀ
BuOK 10 mol%) of benzil 1a and aryl aldehydes 2b-i
displaying halogen electron withdrawing groups, electron
neutral, and electron donating substituents (ꢀMe, ꢀOMe).19 In
agreement with our previous findings, a moderate propensity of
compounds
3
to rearrange into the isomeric benzoylated
2 | J. Name., 2012, 00, 1-3
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Table 2. Substrate scope for the desymmetrization of symmetrical benzils 1.
O
O
t-BuOK
(10 mol %)
O
O
NH4NO3
(3 equiv.)
Ar
Ar
'
Ar
Ar
H
O
Ar
Ar
'
Ar
Ar
'
+
+
Ar
Ar
O
O
O
O
Ar
'
DMSO, RT
AcOH-TFA (2:1)
MW 150 °C, 2 h
O
O
1a-e
2b-m
3
7
4
Entry
1
2
3
(%)a
7
(%)a
4
Entry
1
2
3
(%)a
7
(%)a
4
(%,b %c)
(%,b %c)
Br
O
O
2b
2f
1a
(Ar = Ph)
3ab
(95 %)
7ab
(0 %)
1b
3bf
(86 %)
7bf
(5 %)
1
9
(Ar =4-BrC6H4)
(Ar
'
= 2-ClC6H4)
(Ar
'
=3-BrC6H4)
Cl
O
O
Br
4ab
4bf
(85%, 78%)
(87%, 73%)
O
O
2c
2h
1a
(Ar = Ph)
3ac
(87 %)
7ac
(0 %)
1b
3bh
(71 %)
7bh
(0 %)
10d
2
(Ar =4-BrC6H4)
(Ar
'
= 2-BrC6H4)
(Ar
'
=2-MeC6H4)
Br
O
Me
Br
O
Br
4ac
(74%, 65%)
4bh
(61%, 36%)
Cl
O
O
2d
2f
1a
(Ar = Ph)
3ad
(76 %)
7ad
(19 %)
1c
3cf
(86 %)
7cf
(5 %)
11e
3
(Ar =4-MeC6H4)
(Ar
'
'
= 4-ClC6H4)
(Ar
'
=3-BrC6H4)
O
O
4cf
Me
4ad
(84%, 76%)
(75%, 62%)
Br
O
O
2e
2h
1a
(Ar = Ph)
3ae
(46 %)
7ae
(27 %)
1c
3ch
(52 %)
7ch
(0 %)
12d
4
(Ar =4-MeC6H4)
(Ar
= 4-BrC6H4)
(Ar
'
=2-MeC6H4)
O
Me
O
4ch
Me
4ae
(79%, 61%)
(73%, 35%)
Br
O
O
2f
2j
1a
(Ar = Ph)
3af
(88 %)
7af
(5 %)
1a
(Ar =Ph)
3aj
(78 %)
7aj
(0 %)
5
13
CF3
O
(Ar
'
=3-BrC6H4)
(Ar
'
=2-CF3C6H4)
O
4af
4aj
(85%, 71%)
(82%, 60%)
O
O
2g
2c
1a
(Ar = Ph)
3ag
(58 %)
7ag
(0 %)
1d
3dc
(79%)
7dc
(0 %)
14f
6d
(Ar
'
=1-naphthyl)
(Ar =4-CF3C6H4) (Ar
'
= 2-BrC6H4)
O
Br
O
F3C
4ag
4dc
(73%, 40%)
(77%, 51%)
O
O
2h
2m
=2-furyl)
1a
(Ar = Ph)
3ah
(90 %)
7ah
(0 %)
1a
(Ar =Ph)
3am
(8 %)
7am
(84 %)
7d
15
O
(Ar
'
=2-MeC6H4)
(Ar
'
Me
O
O
4ah
4am
(85%, 73%)
(17%, 11%)
O
O
N
2i
2b
1a
(Ar = Ph)
3ai
(71 %)
7ai
(0 %)
1e
3eb
(95 %)
7eb
(0 %)
16g
(Ar = 2-pyridyl)
(Ar
'
=2-OMeC6H4)
(Ar' = 2-ClC6H4)
8d
Cl
OMe
O
O
4ai
(70%, 45%)
4eb
(25%, 21%)
aIsolated yield. b Yield of 4 starting from isolated 3 + 7. c Yield of 4 strating from 1 by the oneꢀpot twoꢀstep procedure. dFirst step performed at 50 °C with 3
equiv. of 2. eFirst step performed with 2 equiv. of 1c. fFirst step performed with 3 equiv. of 2. gFirst step performed with Cs2CO3 (20 mol%) as the catalyst
.
benzoins
(entries 3 and 4) and, to a much lower extent, from meta
substituted aldehydes (entry 5).18f,26 The isomerization is (Scheme 3). While this side reaction can be almost suppressed
7
was observed when starting from paraꢀsubstituted supposed to proceed through intramolecular transesterification
ꢀ
of the enolate intermediate formed from by deprotonation
5
3
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by lowering the base loading (5 mol%) and the reaction turned out to be unsuitable coupling partners because only trace
temperature (0 °C) at the expense, however, of the reaction time amounts of the corresponding benzoylated benzoins 3/7 were
and benzil conversion,19 in this study it did not represent a limit obtained. Nevertheless, the low reactivity of nitro and cyano
of the whole procedure since both
formation of
over selectivity in the formation of benzoylated benzoins
3 and 7 concur to the substituted aromatic aldehydes in benzoin condensations has
4
. Therefore, conversion efficiency was privileged been previously observed even using cyanide and NHCs
3
catalysts.18f,20
when staring from metaꢀ and paraꢀsubstituted aldehydes
2
.
Overall, a good tolerance to the quite harsh oxidation
conditions was detected for the majority of functional groups
investigated in this study (entries 1ꢀ14). Exceptions were the
furyl and pyridyl substituents as reflected by the low yields of
isolated unsymmetrical benzils 4am and 4eb, respectively
(entries 15ꢀ16). While degradation to several byꢀproducts was
O
O
B
Ar
'
Ar'
Ar
Ar
O
O
O
O
BH
5
3
Ar
observed in the oxidation of furfuralꢀderived benzoin 7am,
conversion of pyridyl intermediate 3eb into the target benzil
4eb (25%) was accompanied by the formation of a major byꢀ
Ar
O
Ar
'
Ar
O
product tentatively assigned as the corresponding pyridyl
Nꢀ
oxide derivative.28
4
O
O
BH
O
Ar
Ar'
O
Ar
Ar'
Conclusion
Ar
Ar
B
6
O
7
O
In summary, we have demonstrated that a practical twoꢀstep
procedure for the desymmetrization of symmetrical benzils can
be pursued using environmental benign conditions and lowꢀcost
reactants and catalyst. Indeed, the synthetic sequence relied on
the chemoselective crossꢀbenzoin reaction of symmetrical
benzils with aromatic aldehydes catalyzed by the methyl
sulfinyl (dimsyl) anion, and the subsequent microwaveꢀassisted
oxidation of the benzoylated benzoin intermediates with
NH4NO3. The optimization of a oneꢀpot procedure for the
above sequence further increased the level of efficiency of the
disclosed strategy by minimization of timeꢀconsuming and
expensive isolation steps. Given the wide availability of
symmetrical benzils and aromatic aldehydes, this methodology
should permit access to a large number of unsymmetrical
benzils with a broad range of structural elements of diversity
for an extensive exploration of their properties in medicinal1a,29
and synthetic chemistry.30
Scheme 3. Rearrangement of benzoylated benzoins
3 into the isomers 7.
In a first protocol towards benzils
4
, intermediates
3
7
were
, and
isolated, eventually with the corresponding isomers
subjected to the optimized oxidation procedure using the
NH4NO3/AcOHꢀTFA/MW system. Yields of unsymmetrical
benzils
4 (entries 1ꢀ8) scored from acceptable to very good (70ꢀ
85%, first yield value in bracket) irrespective of 3/7 isomeric
composition, as proved by control experiments.27 This
promising result was the prerequisite for the development of a
reliable oneꢀpot process by simply interlocking the two
reactivity steps. Accordingly, the symmetrical benzil 1a and
aryl aldehyde
2 were dissolved in DMSO and then t-BuOK (10
mol%) was added in one portion under an argon atmosphere.
After completion of the reaction (TLC analysis), the resulting
solution containing the benzoylated benzoin
3 (or the 3/7
mixture) was neutralized with a small amount of AcOH and
freezeꢀdried. Subsequently, the residue was reꢀdissolved in
AcOHꢀTFA and, after addition of NH4NO3, heated by MW
Experimental section
Potassium tertꢀbutoxide was purified by sublimation (200ꢀ220
°C at 5 mmHg) using a Büchi glass oven B580 in the
sublimation mode. Liquid aldehydes were freshly distilled
before their utilization. Reactions were monitored by TLC on
silica gel 60 F254 with detection by charring with
phosphomolybdic acid. Flash column chromatography was
irradiation. Finally, the unsymmetrical benzil
4 was recovered
by aqueous workꢀup and chromatography. It is important to
stress that quenching the first condensation reaction with acidic
aqueous solutions promoted extensive decomposition of 3.
The scope and limitations of the disclosed oneꢀpot, twoꢀstep
procedure were finally investigated by also considering the
utilization of substituted benzils 1b-d (Ar = 4ꢀBrPh, 4ꢀMePh, 4ꢀ
CF3Ph), 2,2’ꢀpyridyl 1e, and (hetero)aromatic aldehydes 2j-m
displaying common electron withdrawing substituents (ꢀCF3, ꢀ
NO2, ꢀCN) and the electron rich furyl group. As far as the
efficiency of the crossꢀbenzoin is concerned, it resulted that the
electronic feature of the aryl substituent on the acceptor
1
performed on silica gel 60 (230ꢀ400 mesh). H (400 MHz) and
13C (75 MHz) NMR spectra were recorded in CDCl3 solutions
at room temperature. Peaks assignments were aided by Hꢀ1H
1
COSY and gradientꢀHMQC/HMBC experiments. ESIꢀMS
analyses were performed in positive ion mode with samples
dissolved in 10 mM solution of ammonium formate in 1:1
MeCN/H2O. For accurate mass measurements, the compounds
were analyzed in positive ion mode by Agilent 6520 HPLCꢀ
Chip Q/TOFꢀMS (nanospray) using a quadrupole, a hexapole,
and a timeꢀofꢀflight unit to produce spectra. The capillary
source voltage was set at 1700V; the gas temperature and
drying gas were kept at 350°C and 5 L/min, respectively. MS
analyzer was externally calibrated with ESIꢀL low
concentration tuning mix from m/z 118 to 2700 to yield
accuracy below 5 ppm. Accurate mass data were collected by
directly infusing samples in 40/60 H2O/ACN 0.1% TFA into
the system at a flow rate of 0.4 L/min. Elemental analyses
were performed with FLASH 2000 Series CHNS/O analyzer
(ThermoFisher Scientific). Microwaveꢀassisted reactions were
aldehyde
yield of
2
was the most important factor determining the final
4
(second value in bracket). More precisely, electronꢀ
deficient aromatic aldehydes afforded the best reaction
outcomes (entries 1ꢀ5, 9, 13, and 16), whereas electronꢀ
donating groups on either αꢀdiketone 1 or aldehyde 2 produced
less remarkable results (entries 8, 10, and 12). Some particular
comments have to be made about 4ꢀnitro and 4ꢀcyano
benzaldehydes 2k,l (not shown), and 2ꢀfurfuraldehyde 2m as
acceptors. The latter was highly reactive in the crossꢀbenzoin
reaction with benzil 1a affording, however, the rearranged
benzoylated benzoin 7am as the major coupling product. By
contrast, 4ꢀnitrobenzaldehyde 2k and 4ꢀcyanobenzaldehyde 2l
4 | J. Name., 2012, 00, 1-3
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carried out using a singleꢀmode cavity dedicated reactor
(Biotage InitiatorTM). Reactions were performed with
temperatureꢀcontrolled programs in glass vials (0.5ꢀ2 or 2ꢀ5 mL
depending on the scale) sealed with a Teflon septum.
Temperatures were measured externally by an IR sensor. The
reaction time was counted when the reaction mixture reached
the stated temperature. Pressure was measured by a nonꢀ
invasive sensor integrated into the cavity lid. Residual water (%
w/w) of commercially available (SigmaꢀAldrich) anhydrous
DMSO (0.016%) was determined by Fisher analysis with the
AcOEt (3
×
15 mL). The combined organic phases were dried
(Na2SO4), concentrated, and eluted from a column of silica gel
with 30:1 cyclohexaneꢀAcOEt to give 1a
.
Entry 7. A vigorously stirred mixture of 3a (158 mg, 0.50
mmol), AcOH (1 mL), and trifluoroacetic acid (TFA, 2 mL)
was saturated with air (by an airꢀfilled balloon) and refluxed for
24 h. Then, the mixture was cooled to room temperature,
diluted with AcOEt (20 mL), and washed with cold (0 °C)
saturated Na2CO3 solution (2
dried (Na2SO4), concentrated, and eluted from a column of
silica gel with 30:1 cyclohexaneꢀAcOEt to give 1a
Entry 8. A vigorously stirred mixture of 3a (158 mg, 0.50
ꢀDiketone 1d was synthesized as described.31 Benzoylated mmol), AcOH (1 mL), and NH4NO3 (400 mg, 5.00 mmol) was
benzoins 3ab 19 3ac 17f 3ad 19 7ad 19 3ah,19 3am 18f 7am 18f
and refluxed for 24 h. Then, the mixture was cooled to room
3ae19 are known compounds. Benzils 4ab 7c 4ac 9a 4ad 7b,c,9a
temperature, diluted with AcOEt (20 mL), and washed with
4ae 7b,c,9a 4af 7b,12c 4ag 6i,12c 4ah 6e 4ai 7c 4cf 8d 4aj 6j and 4am10
× 5 mL). The organic
× 5 mL). The organic phase was
756 KF Coulometer (Metrohm).
aldehydes 2a-m are commercially available (SigmaꢀAldrich).
αꢀDiketones 1a-c,e and
.
α
,
,
,
,
,
,
,
,
,
,
,
,
,
,
,
,
,
cold (0 °C) saturated Na2CO3 solution (2
are known compounds.
phase was dried (Na2SO4), concentrated, and eluted from a
column of silica gel with 30:1 cyclohexaneꢀAcOEt to give 1a
.
Optimization Study of the oxidation reaction of benzoylated
benzoin 3a (Table 1).
Entries 1-2. A mixture of 3a (158 mg, 0.50 mmol), 1 N NaOH
(1 mL, 1 mmol), and the stated solvent (1 mL) was saturated
with air (by an airꢀfilled balloon) and stirred at room
temperature for 16 hours. Then, the mixture was diluted with
Entries 9-11. A 0.5ꢀ2.0 mL process vial was filled with 3a (158
mg, 0.5 mmol), AcOH (1 mL), and the stated amount of
NH4NO3 (5.00 or 2.50 mmol). The vial was sealed with the
Teflon septum and aluminium crimp by using an appropriate
crimping tool. The vial was then placed in its correct position in
the Biotage Initiator cavity where irradiation was performed at
H2O (5 mL) and extracted with Et2O (2
× 15 mL). The 150 °C for the stated reaction time. After the full irradiation
combined organic phases were dried (Na2SO4), concentrated, sequence was completed, the vial was cooled to room
and eluted from a column of silica gel with 30:1 cyclohexaneꢀ temperature and then opened. The mixture was diluted with
AcOEt to give 1a as a yellow solid.
AcOEt (20 mL), and washed with cold (0 °C) saturated Na2CO3
solution (2 5 mL). The organic phase was dried (Na2SO4),
concentrated, and eluted from a column of silica gel with 30:1
cyclohexaneꢀAcOEt to give 1a
Entries 12-13. A 0.5ꢀ2.0 mL process vial was filled with 3a
(158 mg, 0.5 mmol), AcOH (0.66 mL), TFA (0.33 mL) and
NH4NO3 (120 mg, 1.50 mmol). The vial was sealed with the
Entry 3. To a cooled (0°C), stirred solution of 3a (158 mg, 0.50
mmol) in anhydrous THF (5 mL), was added NaH (60%
dispersion in mineral oil, 40 mg, 1.00 mmol) in one portion.
After the addition, the mixture was allowed to warm to room
temperature, saturated with air (by an airꢀfilled balloon), and
stirred for 16 hours. Then, the mixture was diluted with 0.1 M
×
.
NaHCO3 (10 mL) and extracted with AcOEt (2
× 15 mL). The Teflon septum and aluminium crimp by using an appropriate
combined organic phases were dried (Na2SO4), concentrated, crimping tool. The vial was then placed in its correct position in
and eluted from a column of silica gel with 30:1 cyclohexaneꢀ the Biotage Initiator cavity where irradiation was performed at
AcOEt to give 1a
.
150 °C for the stated reaction time. After the full irradiation
Entry 4. To a vigorously stirred solution of 3a (158 mg, 0.50 sequence was completed, the vial was cooled to room
mmol)
in
DMSO
(1
mL)
was
added
1,8ꢀ temperature and then opened. The mixture was diluted with
AcOEt (20 mL), and washed with cold (0 °C) saturated Na2CO3
diazabicyclo[5.4.0]undecꢀ7ꢀene (DBU, 149
ꢀ
L, 1.00 mmol) in
one portion. The mixture was saturated with air (by an airꢀfilled solution (2
×
5 mL). The organic phase was dried (Na2SO4),
balloon) and stirred at room temperature for 16 hours. Then, the concentrated, and eluted from a column of silica gel with 30:1
mixture was diluted with H2O (5 mL) and extracted with Et2O cyclohexaneꢀAcOEt to give 1a. In entry 13, the mixture was
degassed under vacuum and saturated with argon (by an argonꢀ
filled balloon) three times before irradiation.
(2
(Na2SO4), concentrated, and eluted from a column of silica gel
with 30:1 cyclohexaneꢀAcOEt to give 1a
Entry 5. To a vigorously stirred solution of 3a (158 mg, 0.50 General Procedure for the Cross-Benzoin Reactions of
× 15 mL). The combined organic phases were dried
.
α
-
mmol)
in
AcOEt
(1
mL)
was
added
1,8ꢀ
Diketones 1 with Aldehydes 2 (Table 2, columns 4-5 and 10-
11).
diazabicyclo[5.4.0]undecꢀ7ꢀene (DBU, 149
ꢀL, 1.00 mmol) in
one portion. The mixture was saturated with air (by an airꢀfilled To a vigorously stirred mixture of
balloon), warmed to 70°C, and stirred at that temperature for 24 aldehyde (1.00 mmol), and anhydrous DMSO (2 mL),
hours. Then, the mixture was cooled to room temperature, potassium tertꢀbutoxide (11 mg, 0.10 mmol) was added in one
αꢀdiketone 1 (1.00 mmol),
2
portion. Then, the mixture was degassed under vacuum and
saturated with argon (by an argonꢀfilled balloon) three times.
The mixture was stirred at the stated temperature (Table 2) until
complete disappearance or best conversion of the starting
diketone was detected (TLC analysis, ca. 1ꢀ16 h). Then, the
mixture was diluted with H2O (5 mL) and extracted with Et2O
diluted with H2O (5 mL) and extracted with AcOEt (3
mL). The combined organic phases were dried (Na2SO4),
concentrated, and eluted from a column of silica gel with 30:1
× 15
cyclohexaneꢀAcOEt to give 1a
Entry 6. To a vigorously stirred solution of 3a (158 mg, 0.50
mmol) in AcOEt (1 mL) was added 1,8ꢀ
diazabicyclo[5.4.0]undecꢀ7ꢀene (DBU, 149 L, 1.00 mmol) in
.
(2
× 25 mL). The combined organic phases were dried
ꢀ
(Na2SO4), concentrated, and eluted from a column of silica gel
with the suitable elution system to give the benzoylated
one portion. The mixture was saturated with oxygen (by an
oxygenꢀfilled balloon), warmed to 70°C, and stirred at that
temperature for 24 hours. Then, the mixture was cooled to room
temperature, diluted with H2O (5 mL) and extracted with
benzoins
3 eventually containing isomers 7.
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 5

Organic & Biomolecular Chemistry
Page 6 of 11
VJieowuArrtnicalelONnlainme e
ARTICLE
DOI: 10.1039/C4OB00759J
(395.2): 396.5 [M + H]+. HRMS (ESI) m/z calcd for
1-(2-Chlorophenyl)-2-oxo-2-phenylethyl benzoate (3ab):
Column chromatography with 20:1 cyclohexaneꢀAcOEt C21H15BrO3 [M]+ 394.0205, found 394.0219. Found: C, 63.58;
afforded 3ab19 (332 mg, 95%) as a white foam. H NMR: δ = H, 3.61. C21H15BrO3 requires C, 63.81; H, 3.83%.
1
8.12ꢀ8.07 (m, 2 H, Ar), 8.02ꢀ7.98 (m, 2 H, Ar), 7.60ꢀ7.40 (m, 8
H, Ar), 7.44 (s, 1 H, Hꢀ1), 7.36ꢀ7.24 (m, 2 H, Ar); 13C NMR: δ
1-(Naphthalen-1-yl)-2-oxo-2-phenylethyl benzoate (3ag):
= 193.3, 165.8, 134.9, 134.4, 134.2, 133.8, 133.4,131.8, 130.8, For the synthesis of 3ag three equiv. of aldehyde 2g were used
130.4, 130.2, 130.1, 130.0, 129.9, 129.5, 129.2,129.0, 128.8, and the reaction was performed at 50 °C. Column
128.4, 127.6, 74.0.
chromatography with 20:1 cyclohexaneꢀAcOEt afforded 3ag
1
(212 mg, 58%) as a yellow amorphous solid. H: δ = 8.34 (d,
J
= 8.5 Hz, 1 H, Ar), 8.13ꢀ8.07 (m, 1 H, Ar), 7.96ꢀ7.90 (m, 3 H,
1-(2-Bromophenyl)-2-oxo-2-phenylethyl benzoate (3ac):
Column chromatography with 25:1 cyclohexaneꢀAcOEt Ar), 7.85 (s, 1 H, Hꢀ1), 7.67ꢀ7.51 (m, 4 H, Ar), 7.50ꢀ7.39 (m, 4
1
afforded 3ac17f (344 mg, 87%) as a white amorphous solid. H H, Ar), 7.39ꢀ7.29 (m, 3 H, Ar); 13C NMR: δ = 194.0, 166.1,
NMR: δ = 8.13ꢀ8.05 (m, 2 H, Ar), 8.05ꢀ7.96 (m, 2 H, Ar), 7.67 134.7, 134.2, 133.5, 133.4, 131.5, 130.4, 130.1, 129.9, 129.3,
(dd,
J = 7.9, 1.4 Hz, 1 H, Ar), 7.61ꢀ7.52 (m, 1 H, Ar), 7.54 (s, 1 129.1, 128.7, 128.6, 128.4, 127.4, 126.3, 125.4, 123.3, 75.6.
H, Hꢀ1), 7.53ꢀ7.50 (m, 1 H, Ar), 7.49ꢀ7.39 (m, 5 H, Ar), 7.36ꢀ ESIꢀMS (366.4): 367.7 [M + H]+. HRMS (ESI) m/z calcd for
7.20 (m, 2 H, Ar); 13C NMR δ = 193.4, 165.7, 133.8, 133.6, C25H19O3 [M]+ 366.1256, found 366.1281. Found: C, 81.88; H,
133.5, 133.4, 131.0, 130.6, 130.6, 130.1, 129.1, 128.8, 128.7, 4.68. C25H18O3 requires C, 81.95; H, 4.95%.
128.4, 128.2, 124.7, 76.6. Found: C, 63.71; H, 3.69.
C21H15BrO3 requires C, 63.81; H, 3.83%.
2-Oxo-2-phenyl-1-(o-tolyl)ethyl benzoate (3ah): For the
synthesis of 3ah three equiv. of aldehyde 2h were used and the
reaction was performed at 50 °C. Column chromatography with
2-(4-Chlorophenyl)-2-oxo-1-phenylethyl benzoate (7ad):
Column chromatography with 20:1 cyclohexaneꢀAcOEt gave 12:1 cyclohexaneꢀAcOEt afforded 3ah19 (297 mg, 90%) as a
1
1
7ad19 (66 mg, 19%) as first eluted compound. H NMR: δ = white amorphous solid. H NMR: δ = 8.14ꢀ8.08 (m, 2 H, Ar),
8.14ꢀ8.08 (m, 2 H, Ar), 7.94ꢀ7.90 (m, 2 H, Ar), 7.60ꢀ7.50 (m, 2 7.92ꢀ7.86 (m, 2 H, Ar), 7.60ꢀ7.37 (m, 8 H, Ar), 7.32ꢀ7.14 (m, 2
H, Ar), 7.48ꢀ7.32 (m, 8 H, Ar), 7.03 (s, 1 H, Hꢀ1); 13C NMR: δ H, Ar), 7.29 (s, 1 H, Hꢀ1), 2.50 (s, 3 H, CH3); 13C NMR: δ =
= 192.6, 166.0, 133.5, 130.2ꢀ128.5 (17 C), 77.9.
194.2, 166.1, 137.3, 135.0, 133.4, 133.3, 132.3, 131.3, 130.0ꢀ
128.4 (11 C), 126.7, 75.6, 19.5. ESIꢀMS (330.4): 353.7 [M +
Na]+. HRMS (ESI) m/z calcd for C22H19O3 [M + H]+ 331.1334,
1-(4-Chlorophenyl)-2-oxo-2-phenylethyl benzoate (3ad):
Column chromatography with 20:1 cyclohexaneꢀAcOEt gave found 331.1358. Found: C, 79.65; H, 5.68. C22H18O3 requires
3ad19 (266 mg, 76%) as second eluted compound. 1H NMR: δ = C, 79.98; H, 5.49%.
8.14ꢀ8.06 (m, 2 H, Ar), 8.00ꢀ7.94 (m, 2 H, Ar), 7.60ꢀ7.32 (m,
10 H, Ar), 7.06 (s, 1 H, Hꢀ1); 13C NMR: δ = 193.4, 165.9,
1-(2-Methoxyphenyl)-2-oxo-2-phenylethyl benzoate (3ai):
135.4, 134.5, 133.7, 133.5, 130.0ꢀ128.4 (14 C), 77.3.
For the synthesis of 3ai three equiv. of aldehyde 2i were used
and the reaction was performed at 50 °C. Column
chromatography with 20:1 cyclohexaneꢀAcOEt afforded 3ai
2-(4-Bromophenyl)-2-oxo-1-phenylethyl benzoate (7ae):
Column chromatography with 20:1 cyclohexaneꢀAcOEt gave (246 mg, 71%) as a white amorphous solid. 1H NMR: δ = 8.15ꢀ
1
7ae (106 mg, 27%) as first eluted compound. H NMR: δ = 8.07 (m, 2 H, Ar), 8.08ꢀ7.99 (m, 2 H, Ar), 7.59 (s, 1 H, Hꢀ1),
8.15ꢀ8.06 (m, 2 H, Ar), 7.89ꢀ7.82 (m, 2 H, Ar), 7.60ꢀ7.50 (m, 5 7.58ꢀ7.49 (m, 2 H, Ar), 7.49ꢀ7.38 (m, 5 H, Ar), 7.38ꢀ7.30 (m, 1
H, Ar), 7.48ꢀ7.34 (m, 5 H, Ar), 7.01 (s, 1 H, Hꢀ1); 13C NMR: δ H, Ar), 7.01ꢀ6.90 (m, 2 H, Ar), 3.92 (s, 3 H, CH3); 13C NMR: δ
= 192.9, 166.1, 134.8, 133.5, 133.4, 132.1, 130.4, 130.0, 129.5, = 194.0, 166.2, 156.7, 134.7, 133.4, 133.2, 130.8, 130.0, 129.9,
129.3, 129.1, 128.8, 128.6, 128.5, 77.9. ESIꢀMS (395.2): 434.8 129.7, 128.7, 128.5, 128.35, 122.3, 121.2, 111.3, 71.6, 55.8.
[M + K]+. HRMS (ESI) m/z calcd for C21H16BrO3 [M + H]+ ESIꢀMS (346.4): 347.7 [M + H]+. HRMS (ESI) m/z calcd for
395.0283, found 395.0240. Found: C, 63.55; H, 4.62. C22H19O4 [M + H]+ 347.1283, found 347.1298. Found: C,
C21H15BrO3 requires C, 63.81; H, 3.83%.
76.44; H, 5.12. C22H18O4 requires C, 76.29; H, 5.24%.
1-(4-Bromophenyl)-2-oxo-2-phenylethyl benzoate (3ae): 1-(3-Bromophenyl)-2-(4-bromophenyl)-2-oxoethyl
4-
Column chromatography with 20:1 cyclohexaneꢀAcOEt gave bromobenzoate (3bf): For the synthesis of 3bf 6 mL of solvent
1
3ae (182 mg, 46%) as second eluted compound. H NMR: δ = were used. Column chromatography with 30:1 cyclohexaneꢀ
1
8.15ꢀ8.06 (m, 2 H, Ar), 8.02ꢀ7.93 (m, 2 H, Ar), 7.63ꢀ7.49 (m, 4 AcOEt afforded 3bf (475 mg, 86%) as a white foam. H NMR:
H, Ar), 7.49ꢀ7.35 (m, 6 H, Ar), 7.04 (s, 1 H, Hꢀ1); 13C NMR: δ δ 7.98ꢀ7.92 (m, 2 H, Ar), 7.85ꢀ7.80 (m, 2 H, Ar), 7.71ꢀ7.66 (m,
= 193.4, 165.9, 134.5, 133.8, 133.6, 132.8, 132.4, 130.3, 130.0, 1 H, Ar), 7.63ꢀ7.55 (m, 4 H, Ar), 7.55ꢀ7.48 (m, 1 H, Ar), 7.49ꢀ
129.7, 129.2, 128.8, 128.5, 123.7, 77.4. ESIꢀMS (395.2): 418.3 7.43 (m, 1 H, Ar), 7.31ꢀ7.26 (m, 1 H, Ar), 6.94 (s, 1 H, Hꢀ1);
[M + Na]+. HRMS (ESI) m/z calcd for C21H15BrO3 [M]+ 13C NMR: δ = 191.8, 164.9, 135.0, 132.7, 132.6, 132.37, 132.0,
394.0205, found 394.0227. Found: C, 63.99; H, 4.01. 131.7, 131.3, 130.6, 130.0, 129.0, 128.7, 127.6, 127.0, 123.1,
C21H15BrO3 requires C, 63.81; H, 3.83%.
76.8. ESIꢀMS (553.0): 576.5 [M + Na]+. HRMS (ESI) m/z calcd
for C21H14Br3O3 [M + H]+ 550.8493, found 550.8478. Found:
C, 45.48; H, 2.50. C21H13Br3O3 requires C, 45.61; H, 2.37%.
1-(3-Bromophenyl)-2-oxo-2-phenylethyl benzoate (3af):
Column chromatography with 20:1 cyclohexaneꢀAcOEt
afforded 3af (347 mg, 88%) as a white amorphous solid. H
1
2-(4-Bromophenyl)-2-oxo-1-(o-tolyl)ethyl 4-bromobenzoate
NMR: δ = 8.16ꢀ8.07 (m, 2 H, Ar), 8.03ꢀ7.94 (m, 2 H, Ar), 7.76ꢀ (3bh): For the synthesis of 3bh 6 mL of solvent and three
7.69 (m, 1 H, Ar), 7.62ꢀ7.52 (m, 2 H, Ar), 7.51ꢀ7.38 (m, 6 H, equiv. of aldehyde 2h were used; the reaction was performed at
Ar), 7.30ꢀ7.24 (m, 1 H, Ar), 7.04 (s, 1 H, Hꢀ1); 13C NMR: δ 50 °C. Column chromatography with 30:1 cyclohexaneꢀAcOEt
1
=193.2, 165.8, 135.89, 134.4, 133.8, 133.5, 132.5, 131.5, 130.6, afforded 3bh (341 mg, 71%) as a white amorphous solid. H
130.0, 129.3, 129.1, 128.8, 128.5, 127.2, 123.1, 76.9. ESIꢀMS NMR: δ = 7.97ꢀ7.92 (m, 2 H, Ar), 7.75ꢀ7.69 (m, 2 H, Ar), 7.61ꢀ
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

Page 7 of 11
Journal Name
Organic & Biomolecular Chemistry
View Article Online
ARTICLE
DOI: 10.1039/C4OB00759J
7.50 (m, 4 H, Ar), 7.33ꢀ7.24 (m, 4 H, Ar), 7.19 (s, 1 H, Hꢀ1), C23H13BrF6NaO3 [M+ Na]+ 552.9850, found 552.9821. Found:
2.51 (s, 3 H, CH3); 13C NMR: δ = 193.1, 165.3, 137.2, 134.6, C, 52.67; H, 2.11. C23H13BrF6O3 requires C, 52.00; H, 2.47%.
133.5, 132.0, 131.8, 131.7, 131.5, 130.1, 129.8, 129.5, 128.8,
128.65, 128.1, 126.8, 75.7, 19.4. ESIꢀMS (488.2): 489.6 [M + 1-(Furan-2-yl)-2-oxo-2-phenylethyl benzoate (3am): Column
H]+. HRMS (ESI) m/z calcd for C22H17Br2O3 [M + H]+ chromatography with 10:1 cyclohexaneꢀAcOEt gave 3am18f (25
1
486.9544, found 486.9531. Found: C, 54.29; H, 3.45. mg, 8%) as first eluted compound. H NMR: δ = 8.15ꢀ8.10 (m,
C22H16Br2O3 requires C, 54.13; H, 3.30%.
2 H, Ar), 8.02ꢀ7.96 (m, 2 H, Ar), 7.60ꢀ7.50 (m, 2 H, Ar), 7.48ꢀ
7.40 (m, 5 H, Ar), 7.19 (s, 1 H, Hꢀ1), 6.55ꢀ6.50 (m, 1 H, Ar),
6.42ꢀ6.35 (m, 1 H, Ar); 13C NMR: δ = 190.9, 165.9, 147.0,
144.4, 134.4, 133.8, 133.6, 130.2, 129.2, 128.8, 128.5, 112.2,
111.3, 71.3. ESIꢀMS (306.3): 399.2 [M + K]+. HRMS (ESI) m/z
calcd for C19H14O4 [M]+ 306.0892, found 306.0855. Found: C,
74.12; H, 4.87. C19H14O4 requires C, 74.50; H, 4.61%.
1-(3-Bromophenyl)-2-oxo-2-(
p-tolyl)ethyl 4-methylbenzoate
(3cf): For the synthesis of 3cf two equiv. of
used. Column chromatography with 20:1 cyclohexaneꢀAcOEt
afforded 3cf (364 mg, 86%) as a white amorphous solid. H
NMR: δ = 8.04ꢀ7.94 (m, 2 H, Ar), 7.95ꢀ7.85 (m, 2 H, Ar), 7.72
α
ꢀdiketone 1c were
1
(t,
J = 1.8 Hz, 1 H, Ar), 7.53ꢀ7.43 (m, 2 H, Ar), 7.29ꢀ7.18 (m, 5
2-(Furan-2-yl)-2-oxo-1-phenylethyl benzoate (7am): Column
chromatography with 20:1 cyclohexaneꢀAcOEt gave 7am18f
(257 mg, 84%) as second eluted compound. 1H NMR: δ = 8.16ꢀ
8.10 (m, 2 H, Ar), 7.66ꢀ7.52 (m, 4 H, Ar), 7.48ꢀ7.34 (m, 5 H,
Ar), 7.32ꢀ7.28 (m, 1 H, Ar), 6.90 (s, 1 H, Hꢀ1), 6.48ꢀ6.40 (m, 1
H, Ar); 13C NMR: δ = 182.6, 166.0, 150.7, 147.1, 133.6, 133.5,
130.1, 129.4, 129.4, 129.1, 128.7, 128.5, 119.1, 112.7, 77.4.
ESIꢀMS (306.3): 418.3 [M + Na]+. HRMS (ESI) m/z calcd for
C19H14O4 [M]+ 306.0892, found 306.0840. Found: C, 74.08; H,
4.20. C19H14O4 requires C, 74.50; H, 4.61%.
H, Ar), 7.00 (s, 1 H, Hꢀ1), 2.41 (s, 3 H, CH3), 2.38 (s, 3 H,
CH3); 13C NMR: δ = 192.7, 165.6, 144.5, 144.1, 136.1, 132.1,
131.7, 131.2, 130.3, 129.8, 129.3, 128.9, 128.8, 126.9, 126.2,
122.8, 76.8, 26.7, 21.5. ESIꢀMS (423.3): 446.5 [M + Na]+.
HRMS (ESI) m/z calcd for C23H19BrO3 [M]+ 422.0518, found
422.0535. Found: C, 65.38; H, 4.41. C23H19BrO3 requires C,
65.26; H, 4.52%.
2-Oxo-1-(o-tolyl)-2-(p-tolyl)ethyl 4-methylbenzoate (3ch):
For the synthesis of 3ch three equiv. of aldehyde 2h were used
and the reaction was performed at 50 °C. Column
chromatography with 20:1 cyclohexaneꢀAcOEt afforded 3ch
(186 mg, 52%) as a white amorphous solid. 1H NMR: δ = 8.02ꢀ
1-(2-Chlorophenyl)-2-oxo-2-(pyridin-2-yl)ethyl
picolinate
(3eb): For the synthesis of 3eb Cs2CO3 (20 mol%) was used as
the catalyst. Column chromatography with 2:1 cyclohexaneꢀ
7.95 (m, 2 H, Ar), 7.82ꢀ7.76 (m, 2 H, Ar), 7.36 (d,
J = 7.4 Hz, 1
1
AcOEt afforded 3eb19 (335 mg , 95%) as a white foam; H
H, Ar), 7.26ꢀ7.24 (m, 3 H, Ar), 7.23 (s, 1 H, Hꢀ1), 7.22ꢀ7.15
(m, 4 H, Ar), 2.52 (s, 3 H, CH3), 2.40 (s, 3 H, CH3), 2.35 (s, 3
H, CH3); 13C NMR: δ = 193.7, 165.9, 144.1, 143.8, 137.0,
132.4, 132.2, 131.0, 129.8, 129.4, 129.3, 129.1, 128.6, 126.4,
126.4, 75.1, 21.5, 21.5, 19.3. ESIꢀMS (358.5): 397.8 [M + K]+.
HRMS (ESI) m/z calcd for C24H23O3 [M + H]+ 359.1647, found
359.1628. Found: C, 76.44; H, 5.12. C24H22O3 requires C,
80.42; H, 6.19%.
NMR: δ = 8.79ꢀ8.74 (m, 1 H, Ar), 8.62ꢀ8.56 (m, 1 H, Ar), 8.20ꢀ
8.14 (m, 1 H, Ar), 8.09ꢀ8.03 (m, 1 H, Ar), 8.08 (s, 1 H, Hꢀ1),
7.86ꢀ7.74 (m, 2 H, Ar), 7.49ꢀ7.36 (m, 4 H, Ar), 7.30ꢀ7.26 (m, 2
H, Ar); 13C NMR: δ = 193.9, 164.3, 151.3, 150.1, 149.1, 147.5,
136.9, 136.8, 135.2, 131.9, 130.4, 130.3, 130.2, 127.6, 127.1,
127.0, 125.7, 122.8, 75.5.
General Procedure for the oxidation of benzoylated
benzoins 3/7 to asymmetrical benzils 4 (Table 2). Method A.
A 0.5ꢀ2.0 mL process vial was filled with the benzoylated
2-Oxo-2-phenyl-1-(2-(trifluoromethyl)phenyl)ethyl benzoate
(3aj): Column chromatography with 20:1 cyclohexaneꢀAcOEt
1
benzoin
3 or 3/7 isomers mixture (0.5 mmol), AcOH (0.66 mL),
afforded 3aj (299 mg, 78%) as a white amorphous solid. H
TFA (0.33 mL), and NH4NO3 (120 mg, 1.50 mmol). The vial
was sealed with the Teflon septum and aluminium crimp by
using an appropriate crimping tool. The vial was then placed in
its correct position in the Biotage Initiator cavity where
irradiation was performed at 150 °C for 2 h. After the full
irradiation sequence was completed, the vial was cooled to
room temperature and then opened. The mixture was diluted
with AcOEt (20 mL), and washed with cold (0 °C) saturated
NMR: δ = 8.08ꢀ8.04 (m, 2 H, Ar), 7.96ꢀ7.92 (m, 2 H, Ar), 7.82ꢀ
7.77 (m, 1 H, Ar), 7.60ꢀ7.52 (m, 4 H, Ar), 7. 52 (s, 1 H, Hꢀ1),
7.46ꢀ7. 38 (m, 4 H, Ar); 13C NMR: δ = 193.4, 165.6, 134.5,
133.8, 133.5, 132.7, 132.2, 130.9, 130.1, 129.7, 129.5, 129.2,
128.9, 128.8, 128.5, 126.9, 126.8, 125.5, 73.1; 19F NMR (376
MHz: δ = ꢀ58.6 (s, 3 F, CF3). ESIꢀMS (384.3): 407.2 [M +
Na]+. HRMS (ESI) m/z calcd for C22H15F3O3 [M]+ 384.0973,
found 384.0912. Found: C, 68.41; H, 3.70. C22H15F3O3 requires
C, 68.75; H, 3.93%.
Na2CO3 solution (2
(Na2SO4), concentrated, and eluted from a column of silica gel
with the suitable elution system to give the benzil . Final
elution with 10:1 AcOEtꢀMeOH afforded the corresponding
× 5 mL). The organic phase was dried
4
1-(2-Bromophenyl)-2-oxo-2-(4-
(trifluoromethyl)phenyl)ethyl 4-(trifluoromethyl)benzoate
(3dc): For the synthesis of 3dc three equiv. of aldehyde 2c were benzoic acid/benzamide mixture.
used. Column chromatography with 30:1 cyclohexaneꢀAcOEt
1
afforded 3dc (419 mg, 79%) as a white foam. H NMR: δ =
8.24ꢀ8.18 (m, 2 H, Ar), 8.12ꢀ8.06 (m, 2 H, Ar), 7.74ꢀ7.68 (m, 5
H, Ar), 7.53 (s, 1 H, Ar), 7.46ꢀ7.41 (m, 1 H, Ar), 7.39ꢀ7.22 (m,
2 H, Ar); 13C NMR: δ = 192.4, 164.7, 137.0, 135.7, 135.3,
135.2, 135.0, 134.9, 134.7, 134.0, 132.5, 132.3, 131.7, 130.7,
130.6, 129.2, 128.6, 127.5, 126.1, 126.0, 125.9, 125.8, 125.7,
General Procedure for the one-pot, two step synthesis of
benzils 4 (Table 2). Method B.
To a vigorously stirred mixture of
αꢀdiketone 1 (1.00 mmol),
aldehyde (1.00 mmol), and anhydrous DMSO (2 mL) in a
2
0.5ꢀ2.0 mL process vial, potassium tertꢀbutoxide (11 mg, 0.10
mmol) was added in one portion. Then, the mixture was
degassed under vacuum and saturated with argon (by an argonꢀ
filled balloon) three times. The mixture was stirred at the stated
temperature (Table 2) until complete disappearance or best
conversion of the starting diketone was detected (TLC analysis,
125.6, 125.6, 125.4, 124.9, 124.8, 124.8, 122.3, 122.1, 76.8; 19
F
NMR (376 MHz: δ = ꢀ63,2 (s, 3 F, CF3), ꢀ63.3 (s, 3 F, CF3).
ESIꢀMS (531.2): 554.8 [M + Na]+. HRMS (ESI) m/z calcd for
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 7

Organic & Biomolecular Chemistry
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VJieowuArrtnicalelONnlainme e
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DOI: 10.1039/C4OB00759J
ca. 1ꢀ16 h). Then, the mixture was neutralized with AcOH and C14H10BrO2 [M + H]+ 288.9864, found 288.9811. Found: C,
freezeꢀdried. The resulting residue containing the benzoylated 58.45; H, 3.60. C14H9BrO2 requires C, 58.16; H, 3.14%.
benzoin
3 or 3/7 isomers mixture was dissolved in AcOH (1.3
mL mL) and TFA (0.7 mL), then NH4NO3 (240 mg, 3.00 1-(3-bromophenyl)-2-phenylethane-1,2-dione (4af): Method
mmol) was added in one portion. The vial was sealed with the A. Column chromatography with 1.5:1 cyclohexaneꢀCH2Cl2
Teflon septum and aluminium crimp by using an appropriate afforded 4af7b,12c (123 mg, 85%) as a yellow amorphous solid.
1
crimping tool. The vial was then placed in its correct position in Method B: 4af7b,12c (205 mg, 71%). H NMR: δ = 8.12 (t,
J =
the Biotage Initiator cavity where irradiation was performed at 1.7 Hz, 1 H, Ar), 8.00ꢀ7.92 (m, 2 H, Ar), 7.92ꢀ7.84 (m, 1 H,
150 °C for 2 h. After the full irradiation sequence was Ar), 7.82ꢀ7.74 (m, 1 H, Ar), 7.74ꢀ7.63 (m, 1 H, Ar), 7.59ꢀ7.46
completed, the vial was cooled to room temperature and then (m, 2 H, Ar), 7.39 (t, J
= 7.9 Hz, 1 H, Ar); 13C NMR: δ = 193.5,
opened. The mixture was diluted with AcOEt (40 mL), and 192.9, 137.7, 135.2, 134.6, 132.6, 132.5, 130.6, 130.0, 129.1,
128.6, 123.3. ESIꢀMS (289.1): 312.5 [M + Na]+. HRMS (ESI)
washed with cold (0 °C) saturated Na2CO3 solution (2
mL). The organic phase was dried (Na2SO4), concentrated, and
eluted from a column of silica gel with the suitable elution
× 10
m/z calcd for C14H10BrO2 [M + H]+ 288.9864, found 288.9824.
Found: C, 58.01; H, 3.75. C14H9BrO2 requires C, 58.16; H,
3.14%.
system to give the benzil 4. Final elution with 10:1 AcOEtꢀ
MeOH afforded the corresponding benzoic acid/benzamide
mixture.
1-(Naphthalen-1-yl)-2-phenylethane-1,2-dione
(4ag):
Method A. Column chromatography with 32:1 cyclohexaneꢀ
AcOEt afforded 4ag6i,12c (95 mg, 73%) slightly contaminated
by uncharacterized byꢀproducts. Method B. For the synthesis of
4ag three equiv. of aldehyde 2g were used and the benzoin
reaction was performed at 50 °C. Column chromatography with
1.7:1 cyclohexaneꢀCH2Cl2 afforded 4ag6i,12c (104 mg, 40%)
slightly contaminated by uncharacterized byꢀproducts. 1H
1-(2-Chlorophenyl)-2-phenylethane-1,2-dione (4ab): Method
A. Column chromatography with 25:1 cyclohexaneꢀAcOEt
afforded 4ab7c (103 mg, 85%) as a yellow amorphous solid.
Method B: 4ab7c (190 mg, 78%). 1H NMR: δ = 8.07ꢀ8.00 (m, 2
H, Ar), 7.94ꢀ7.88 (m, 1 H, Ar), 7.70ꢀ7.63 (m, 1 H, Ar), 7.58ꢀ
7.49 (m, 3 H, Ar), 7.47ꢀ7.40 (m, 2 H, Ar); 13C NMR: δ = 193.7,
192.0, 134.6, 134.5, 134.0, 133.8, 132.4, 132.1, 130.5, 130.2,
128.9, 127.4. ESIꢀMS (244.0): 245.6 [M + H]+. HRMS (ESI)
m/z calcd for C14H10ClO2 [M + H]+ 245.0369, found 245.0355.
Found: C, 68.90; H, 3.48. C14H9ClO2 requires C, 68.72; H,
3.71%.
NMR: δ = 9.30 (d,
J = 8.5 Hz, 1 H, Ar), 8.13 (d, J = 8.5 Hz, 1
H, Ar), 8.07ꢀ7.98 (m, 2 H, Ar), 7.98ꢀ7.85 (m, 2 H, Ar), 7.81ꢀ
7.70 (m, 1 H, Ar), 7.70ꢀ7.57 (m, 2 H, Ar), 7.57ꢀ7.47 (m, 3 H,
Ar); 13C NMR: δ = 197.2, 194.6, 136.0, 135.1, 134.7, 134.1,
133.3, 130.9, 130.0, 129.5, 129.0, 128.8, 127.2, 127.1, 125.9,
124.4. ESIꢀMS (260.3): 312.5 [M + K]+.
1-(2-Bromophenyl)-2-phenylethane-1,2-dione (4ac): Method
A. Column chromatography with 40:1 cyclohexaneꢀAcOEt
afforded 4ac9a (106 mg, 74%) as a yellow amorphous solid.
Method B: column chromatography with 1.8:1 cyclohexaneꢀ
1-Phenyl-2-(o-tolyl)ethane-1,2-dione (4ah): Method A.
Column chromatography with 40:1 cyclohexaneꢀAcOEt
afforded 4ah6e (95 mg, 85%) as a yellow solid (mp 56ꢀ57 °C).
Method B. For the synthesis of 4ah three equiv. of aldehyde 2h
were used and the benzoin reaction was performed at 50 °C.
1
CH2Cl2 afforded 4ac9a (187 mg, 65%). H NMR: δ = 8.10ꢀ8.03
(m, 2 H, Ar), 7.84ꢀ7.79 (m, 1 H, Ar), 7.70ꢀ7.61 (m, 2 H, Ar),
7.58ꢀ7.49 (m, 2 H, Ar), 7.49ꢀ7.43 (m, 2 H, Ar); 13C: δ = 194.2,
191.5, 136.1, 134.5, 134.4, 133.8, 132.7, 132.6, 130.4, 128.9,
127.9, 121.8. ESIꢀMS (289.1): 312.4 [M + Na]+. HRMS (ESI)
m/z calcd for C14H10BrO2 [M + H]+ 288.9864, found 288.9835.
Found: C, 58.28; H, 3.25. C14H9BrO2 requires C, 58.16; H,
3.14%.
1
4ah6e (163 mg, 73%). H NMR: δ = 8.01ꢀ7.93 (m, 2 H, Ar),
7.70ꢀ7.59 (m, 2 H, Ar), 7.55ꢀ7.45 (m, 3 H, Ar), 7.37ꢀ7.25 (m, 2
H, Ar), 2.70 (s, 3 H, CH3); 13C NMR: δ = 196.8, 194.9, 141.4,
134.7, 133.8, 133.12, 132.6, 131.8, 130.0, 129.1, 126.1, 22.0.
ESIꢀMS (224.2): 225.6 [M + H]+. HRMS (ESI) m/z calcd for
C15H13O2 [M + H]+ 225.0916, found 225.0948. Found: C,
80.61; H, 5.90. C15H12O2 requires C, 80.34; H, 5.39%.
1-(4-Chlorophenyl)-2-phenylethane-1,2-dione (4ad): Method
A. Column chromatography with 30:1 cyclohexaneꢀAcOEt
afforded 4ad9a (102 mg, 84%) as a pale yellow solid (mp 71ꢀ73
1-(2-Methoxyphenyl)-2-phenylethane-1,2-dione
(4ai):
Method A. Column chromatography with 15:1 cyclohexaneꢀ
AcOEt afforded 4ai7c (84 mg, 70%) as a white amorphous
solid. Method B. For the synthesis of 4ai three equiv. of
aldehyde 2i were used and the benzoin reaction was performed
at 50 °C. Column chromatography with 1.6:1 cyclohexaneꢀ
1
°C). Method B: 4ad7b,c,9a (185 mg, 76%). H NMR: δ = 7.98ꢀ
7.87 (m, 4 H, Ar), 7.71ꢀ7.62 (m, 1 H, Ar), 7.56ꢀ7.44 (m, 4 H,
Ar); 13C NMR: δ = 194.1, 193.3, 141.8, 135.3, 133.0, 131.5,
131.4, 130.2, 129.7, 129.3. ESIꢀMS (244.0): 267.3 [M + Na]+.
HRMS (ESI) m/z calcd for C14H9ClO2 [M]+ 244.0291, found
244.0270. Found: C, 70.01; H, 3.45. C14H9ClO2 requires C,
68.72; H, 3.71%.
1
CH2Cl2 afforded 4ai7c (108 mg, 45%). H NMR: δ = 8.06ꢀ7.99
(m, 1 H, Ar), 7.96ꢀ7.89 (m, 2 H, Ar), 7.65ꢀ7.54 (m, 2 H, Ar),
7.54ꢀ7.44 (m, 2 H, Ar), 7.16ꢀ7.08 (m, 1 H, Ar), 6.93 (d,
J = 8.5
Hz, 1 H, Ar), 3.56 (s, 3 H, CH3); 13C NMR: δ = 194.6, 193.5,
160.4, 136.5, 133.8, 132.9, 130.5, 129.3, 128.7, 123.8, 121.5,
112.3, 55.7. ESIꢀMS (240.2): 263.8 [M + Na]+. HRMS (ESI)
m/z calcd for C15H12O3 [M]+ 240.0786, found 240.0711. Found:
C, 74.77; H, 5.27. C15H12O3 requires C, 74.99; H, 5.03%.
1-(4-Bromophenyl)-2-phenylethane-1,2-dione (4ae): Method
A. Column chromatography with 40:1 cyclohexaneꢀAcOEt
afforded 4ae7b,c,9a (114 mg, 79%) as a pale yellow solid (mp 81ꢀ
83 °C). Method B. Column chromatography with 1.3:1
cyclohexaneꢀCH2Cl2 afforded 4ae7b,c,9a (176 mg, 61%). 1H
NMR: δ = 7.99ꢀ7.92 (m, 2 H, Ar), 7.87ꢀ7.81 (m, 2 H, Ar), 7.71ꢀ
7.62 (m, 3 H, Ar), 7.56ꢀ7.47 (m, 2 H, Ar); 13C NMR: δ = 193.9,
193.3, 135.1, 132.8, 132.5, 131.8, 131.3, 130.6, 123.0, 129.1.
ESIꢀMS (289.1): 290.1 [M + H]+. HRMS (ESI) m/z calcd for
1-(3-Bromophenyl)-2-(4-bromophenyl)ethane-1,2-dione
(4bf): Method A. Column chromatography with 1:1
cyclohexaneꢀCH2Cl2 afforded 4bf (158 mg, 87%) as a yellow
amorphous solid. Method B. For the synthesis of 4bf 6 mL of
solvent were used in the benzoin reaction: 4bf (269 mg, 73%).
8 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

Page 9 of 11
Journal Name
Organic & Biomolecular Chemistry
View Article Online
ARTICLE
DOI: 10.1039/C4OB00759J
1H NMR: δ = 8.11 (t,
Ar), 7.71ꢀ7.63 (m, 2 H, Ar), 7.40 (t,
J = 1.8 Hz, 1 H, Ar), 7.90ꢀ7.76 (m, 4 H,
1-(2-Bromophenyl)-2-(4-(trifluoromethyl)phenyl)ethane-
J
= 7.9 Hz, 1 H, Ar); 13C 1,2-dione (4dc): Method A. Column chromatography with 35:1
NMR: δ = 192.1, 191.9, 137.7, 134.2, 132.31, 131.1, 130.6, cyclohexaneꢀAcOEt afforded 4dc (179 mg, 77%) as a yellow
130.5, 130.4, 128.4, 123.2. ESIꢀMS (368.0): 391.5 [M + Na]+. foam. Method B. For the synthesis of 4dc three equiv. of
HRMS (ESI) m/z calcd for C14H9Br2O2 [M + H]+ 366.8969, aldehyde 2c were used in the benzoin reaction. Column
found 366.8911. Found: C, 45.90; H, 2.55. C14H8Br2O2 requires chromatography with 1.3:1 cyclohexaneꢀCH2Cl2 afforded 4dc
C, 45.69; H, 2.19%.
(182 mg, 51%). 1H NMR: δ = 8.24ꢀ8.16 (m, 2 H, Ar), 7.84ꢀ7.76
(m, 3 H, Ar), 7.66ꢀ7.60 (m, 1 H, Ar), 7.55ꢀ7.44 (m, 1 H, Ar);
13C NMR: δ = 193.7, 190.0, 136.0, 135.7, 135.0, 135.4, 134.8,
1-(4-Bromophenyl)-2-(
o-tolyl)ethane-1,2-dione
(4bh):
Method A. Column chromatography with 1.5:1 cyclohexaneꢀ 133.7, 133.6, 132.6, 132.7, 131.7, 130.8, 130.5, 129.2, 128.1,
CH2Cl2 afforded 4bh (92 mg, 61%) as a yellow amorphous 128.0, 126.1, 126.0, 125.9, 125.8, 124.9, 122.2, 121.9 ; 19F
solid. Method B. For the synthesis of 4bh 6 mL of solvent and NMR (376 MHz): δ = ꢀ63.3 (s, 3 F, CF3). ESIꢀMS (357.1):
three equiv. of aldehyde 2h were used in the benzoin reaction 380.4 [M + Na]+. HRMS (ESI) m/z calcd for C15H8BrF3NaO2
that was performed at 50 °C: 4bh (109 mg, 36%). 1H NMR: δ = [M + Na]+ 378.9557, found 378.9511. Found: C, 50.12; H,
7.88ꢀ7.80 (m, 2 H, Ar), 7.70ꢀ7.63 (m, 2 H, Ar), 7.63ꢀ7.56 (m, 1 2.66. C15H8BrF3O2 requires C, 50.45; H, 2.26%.
H, Ar), 7.54ꢀ7.46 (m, 1 H, Ar), 7.37ꢀ7.26 (m, 2 H, Ar), 2.69 (s,
3 H, CH3); 13C NMR: δ = 196.1, 193.6, 141.5, 134.0, 133.0, 1-(Furan-2-yl)-2-phenylethane-1,2-dione (4am): Method A.
132.6, 132.4, 131.8, 131.5, 131.3, 130.3, 126.1, 21.9. ESIꢀMS Column chromatography with 12:1 cyclohexaneꢀAcOEt
(303.1): 326.8 [M + Na]+. HRMS (ESI) m/z calcd for afforded 4am10 (17 mg, 17%) as a yellow oil. Method B: 4am10
1
C15H11BrNaO2 [M + Na]+ 324.9840, found 324.9814. Found: (22 mg, 11%). H NMR: δ = 8.06ꢀ8.00 (m, 2 H, Ar), 7.78ꢀ7.75
C, 59.81; H, 3.12. C15H11BrO2 requires C, 59.43; H, 3.66%.
(m, 1 H, Ar), 7.70ꢀ7.62 (m, 1 H, Ar), 7.55ꢀ7.46 (m, 2 H, Ar),
7.42ꢀ7.38 (m, 1 H, Ar), 6.65ꢀ6.58 (m, 1 H, Ar); 13C NMR: δ =
191.7, 180.2, 149.8, 149.2, 134.5, 132.2, 130.0, 128.8, 123.1,
1-(3-Bromophenyl)-2-(
p
-tolyl)ethane-1,2-dione
(4cf):
Method A. Column chromatography with 25:1 cyclohexaneꢀ 112.7; ESIꢀMS (200.2): 201.5 [M]+. HRMS (ESI) m/z calcd for
AcOEt afforded 4cf8d (113 mg, 75%) as a yellow amorphous C12H8O3 [M]+ 200.0473, found 200.0412. Found: C, 69.78; H,
3.88. C12H8O3 requires C, 72.00; H, 4.03%.
solid. Method B. For the synthesis of 4cf two equiv. of
αꢀ
diketone 1c were used. Column chromatography with 1.6:1
cyclohexaneꢀCH2Cl2 afforded 4cf8d (188 mg, 62%). 1H NMR: δ
1-(2-Chlorophenyl)-2-(pyridin-2-yl)ethane-1,2-dione (4eb):
Method A. Column chromatography with 4:1 cyclohexaneꢀ
AcOEt afforded 4eb (31 mg, 25%) as a yellow amorphous
= 8.11 (t,
J = 1.7 Hz, 1 H, Ar), 7.90ꢀ7.82 (m, 3 H, Ar), 7.80ꢀ
7.73 (m, 1 H, Ar), 7.42ꢀ7.34 (m, 1 H, Ar), 7.34ꢀ7.28 (m, 2 H,
Ar), 2.44 (s, 3 H, CH3); 13C NMR: δ = 193.1, 192.8, 146.3,
137.4, 134.6, 132.3, 130.3, 130.0, 129.9, 129.6, 128.3, 123.1,
21.8. ESIꢀMS (303.1): 304.4 [M + H]+. HRMS (ESI) m/z calcd
for C15H11BrO2 [M]+ 301.9942, found 301.9976. Found: C,
59.21; H, 3.88. C15H11BrO2 requires C, 59.43; H, 3.66%.
1
solid. Method B: 4eb (51 mg, 21%). H NMR: δ = 8.74ꢀ8.68
(m, 1 H, Ar), 8.24ꢀ8.18 (m, 1 H, Ar), 8.14ꢀ8.06 (m, 1 H, Ar),
8.00ꢀ7.90 (m, 1 H, Ar), 7.60ꢀ7.30 (m, 4 H, Ar); 13C NMR: δ =
193.6, 191.7, 150.0, 149.3, 135.0, 132.6, 135.0, 130.3, 129.0,
123.5, 113.1 ESIꢀMS (245.7): 246.8 [M + H]+. HRMS (ESI)
m/z calcd for C13H8ClNO2 [M]+ 245.0244, found 245.0216.
Found: C, 63.70; N, 5.12; H, 3.41. C13H8ClNO2 requires C,
63.56; N, 5.70; H, 3.28%.
1-(o-Tolyl)-2-(p-tolyl)ethane-1,2-dione (4ch): Method A.
Column chromatography with 10:1 cyclohexaneꢀAcOEt
afforded 4ch (87 mg, 73%) as a white amorphous solid. Method
B. For the synthesis of 4ch three equiv. of aldehyde 2h were
used in the benzoin reaction that was performed at 50 °C.
Column chromatography with 1.3:1 cyclohexaneꢀCH2Cl2
Acknowledgements
afforded 4ch (83 mg, 35%). 1H NMR: δ = 7.86 (d,
J
= 8.2 Hz, 2
We gratefully acknowledge University of Ferrara (fondi FAR)
for financial support. Thanks are also given to Mr. P. Formaglio
for NMR spectroscopic experiments, to Mrs. E. Bianchini for
elemental analyses, and to Dr. T. Bernardi for highꢀresolution
mass spectrometric experiments.
H, Ar), 7.63 (dd,
J = 7.8, 1.1 Hz, 1 H,Ar), 7.48 (dt, J = 7.6, 1.3
Hz, 1 H, Ar), 7.36ꢀ7.26 (m, 4 H, Ar), 2.70 (s, 3 H, CH3), 2.44
(s, 3 H, CH3); 13C NMR: δ = 197.0, 194.7, 146.0, 141.4, 133.7,
133.1, 132.6, 131.9, 130.1, 129.8, 128.8, 126.0, 22.0. ESIꢀMS
(238.28): 239.5 [M + H]+. HRMS (ESI) m/z calcd for C16H15O2
[M + H]+ 239.1072, found 239.1080. Found: C, 80.41; H, 5.78.
C16H14O2 requires C, 80.65; H, 5.92%.
Notes and references
Dipartimento di Scienze Chimiche e Farmaceutiche, Laboratorio di Chimica
Organica, Via Fossato di Mortara 17, 44121 Ferrara, Italy
E-mail: olga.bortolini@unife.it - alessandro.massi@unife.it
1-Phenyl-2-(2-(trifluoromethyl)phenyl)ethane-1,2-dione
(4aj): Method A. Column chromatography with 12:1
cyclohexaneꢀAcOEt afforded 4aj6j (114 mg, 82%) as a yellow
†
Electronic Supplementary Information (ESI) available: [1H, 13C, and
19F spectra of compounds
3, 4, and 7]. See DOI: 10.1039/b000000x/
1
amorphous solid. Method B: 4aj6j (167 mg, 60%). H NMR: δ
= 8.12ꢀ8.06 (m, 2 H, Ar), 7.84ꢀ7.78 (m, 1 H, Ar), 7.76ꢀ7.62 (m,
4 H, Ar), 7.60ꢀ7.50 (m, 2 H, Ar); 13C NMR: δ = 193.1, 191.0,
134.9, 134.6, 132.5, 132.1, 131.4, 130.9, 129.0, 128.6, 127.2,
127.2, 124.9, 122.1; 19F NMR (376 MHz): δ = ꢀ57.9 (s, 3 F,
CF3). ESIꢀMS (278.2): 279.5 [M + H]+. HRMS (ESI) m/z calcd
for C15H9F3O2 [M]+ 278.0555, found 278.0511. Found: C,
64.98; H, 3.12. C15H9F3O2 requires C, 64.75; H, 3.26%.
1
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C. W. Lindsley, Org. Lett. 2004, , 1453; (d) A. J. Herrera, M.
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VJieowuArrtnicalelONnlainme e
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DOI: 10.1039/C4OB00759J
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DOI: 10.1039/C4OB00759J
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