Palladium-Catalyzed Carbonylative Synthesis of 2,3-Disubstituted Chromones

Article abstract of DOI:10.1002/adsc.201500858

An unexpected palladium-catalyzed carbonylative synthesis of 2,3-disubstituted chromones has been developed. Starting from 2-bromofluorobenzenes and ketones, the corresponding chromones were produced in good yields. By control experiments, this transformation was found to proceed through a sequential carbonylation/Claisen-Hasse rearrangement/intramolecular nucleophilic aromatic substitution approach (S_NAr). More specifically, the reaction sequence started with a palladium-catalyzed carbonylation of the ketone with o-bromofluorobenzene to give the vinyl benzoates, which subsequently transformed into 1,3-diketones via a Claisen-Hasse rearrangement. The final products were produced after an intramolecular S_NAr reaction of the in situ formed 1,3-diketone.

Full text of DOI:10.1002/adsc.201500858

UPDATES
DOI: 10.1002/adsc.201500858
Palladium-Catalyzed Carbonylative Synthesis of 2,3-Disubstituted
Chromones
Chaoren Shen,a Wanfang Li,a Hongfei Yin,b Anke Spannenberg,a
Troels Skrydstrup,b and Xiao-Feng Wua,*
a
Leibniz-Institut für Katalyse an der Universität Rostock e.V. , Albert-Einstein-Str. 29a, 18059 Rostock, Germany
E-mail: xiao-feng.wu@catalysis.de
Center for Insoluble Protein Structures (inSPIN), Interdisciplinary Nanoscience Center (iNANO), Department of
b
Chemistry, Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark
Received: September 14, 2015; Revised: October 30, 2015; Published online: January 21, 2016
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500858.
Abstract: An unexpected palladium-catalyzed car-
bonylative synthesis of 2,3-disubstituted chromones
has been developed. Starting from 2-bromofluoro-
benzenes and ketones, the corresponding chro-
mones were produced in good yields. By control ex-
periments, this transformation was found to proceed
through a sequential carbonylation/Claisen–Hasse
rearrangement/intramolecular nucleophilic aromatic
substitution approach (SNAr). More specifically, the
reaction sequence started with a palladium-cata-
lyzed carbonylation of the ketone with o-bromo-
fluorobenzene to give the vinyl benzoates, which
subsequently transformed into 1,3-diketones via
a Claisen–Hasse rearrangement. The final products
were produced after an intramolecular SNAr reac-
tion of the in situ formed 1,3-diketone.
harsh reaction conditions (for example, typical reac-
tion temperature of Kostanecki–Robinson reaction
often exceeds 1608C) with poor functional group tol-
erance and formation of undesired side-products such
as coumarins.[1,5a] Besides these name reactions, a two-
step electrophilic cyclization/Suzuki cross-coupling
strategy[8] (Scheme 1, d) and the Rh-catalyzed oxida-
tive coupling of salicylaldehydes with internal sym-
metrical alkynes[9] (Scheme 1, e) have also been de-
veloped and provided alternative accesses to 2,3-di-
substituted chromones. Although cyclocarbonylation
has been applied in the synthesis of chromones, only
3-substituted chromones can be obtained with termi-
nal acetylenes.[10] The above approaches have more or
less limitations in the procedure or the scope of sub-
strates and products. So it is still necessary to diversify
pathways for efficiently preparing functionalized 2,3-
disubstituted chromones from commercially available
starting materials under mild reaction conditions.
As a versatile reaction with more than a thirty-year
history,[11] palladium-catalyzed carbonylation displays
power in preparing various kinds of heterocyclic com-
pounds with carbonyl groups.[12] Our group has fo-
cused on the carbonylative synthesis of heterocycles
during the last few years[13] and recently found that
fusing carbonylation and nucleophilic aromatic substi-
Keywords: carbonylation; chromones; Claisen–
Hasse rearrangement; nucleophilic aromatic substi-
tution; palladium catalysts
Introduction
The chromone moiety is ubiquitous in naturally occur- tution (SNAr) can provide a new pathway for hetero-
ring compounds.[1] Its derivatives exhibit diverse bio- cycles synthesis.[14] In 2014, three examples of chro-
logical[2] and pharmaceutical activities[3] and interest- mones (3a, 3c, and 3i) instead of the expected isochro-
ing fluorescence characteristics.[4] Therefore enriching menones were obtained by us from 2-fluorobromo-
the methods for their preparation is an important benzenes and 2-phenylacetophenone using a palladium
issue in organic synthesis. The Claisen condensation[5] catalyst (Scheme 1, f).[14b] In 2009, Willis and co-work-
(Scheme 1, a), Kostanecki–Robinson reaction[5a,6] ers have reported the palladium-catalyzed carbonyla-
(Scheme 1, b) and Baker–Venkatamaran rearrange- tive cyclization of a-(o-haloaryl)-substituted ke-
ment[7] (Scheme 1, c) are three classical non-catalytic tones,[15] which led to our original proposal of the
pathways for preparing 2,3-disubstituted chromones. products as isochromenones (Scheme 2, a). During
Utilizing these pathways to obtain 2,3-disubstituted our further studies, we found that a Claisen–Hasse re-
chromones inevitably involves a multistep process, arrangement occurred in advance of the nucleophilic
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Palladium-Catalyzed Carbonylative Synthesis of 2,3-Disubstituted Chromones
Scheme 1. Pathways to 2,3-disubstituted chromones.
Scheme 2. The chemoselectivity on carbonylation of the deoxybenzoin substrate.
substitution, which then gave chromones as the prod- Results and Discussion
ucts (Scheme 2, b). Here we wish to report our de-
tailed results on the palladium-catalyzed carbonyla- Initially, commercially obtainable 1-bromo-2-fluoro-
tive synthesis of 2,3-disubstituted chromones from 2- benzene and deoxybenzoin were employed as model
fluoroaryl bromides and ketones (Scheme 1, f). In ad- substrates for the screening of reaction conditions
dition, 13C-labelled experiments were performed using (Table 1). The research was started by investigating
a two-chamber reactor (COware) and 13C-labelled de- the effect of different phosphine ligands on the reac-
oxybenzoin, mono or double labelled 2,3-diphenyl- tion in combination with Pd(OAc)2 as the Pd source
4H-chromen-4-ones were produced in good yields.
and Cs2CO3 as the base in N,N-dimethylacetamide
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Chaoren Shen et al.
Table 1. Optimization of the rfeaction conditions.[a]
enol (O-benzoylation, Scheme 2, a)[14b] or the a-
carbon of the ketone (carbonylative a-arylation,
Scheme 2, b). Hence the chemoselectivity between
forming 1,3-diketone or generating vinyl benzoate is
always taken into account in the carbonylation of
ketone substrates. In order to confirm the chemical
structure of our product, a crystal of the model prod-
uct was prepared and analyzed by X-ray crystallogra-
phy (Figure 1)[17] The confirmation of chromone as
Entry
[Pd]/Ligand
CO pres-
sure [bar]
Yield[b]
1
2
3
4
5
6
7
8
Pd(OAc)2/dppm
Pd(OAc)2/dppe
Pd(OAc)2/dppp
Pd(OAc)2/dppb
Pd(OAc)2/dppb
Pd(OAc)2/dppf
Pd(OAc)2/DPE
Pd(OAc)2/xanthphos
Pd(OAc)2/(t-Bu)3P·HBF4
Pd(OAc)2/BuPAd2
Pd(OAc)2/dppp
Pd(OAc)2/dppp
Pd(OAc)2/dppp
Pd(OAc)2/dppp
35
35
35
35
35
35
35
35
35
35
35
35
35
10
<10%
38%
71%
60%
47%
55%
48%
61%
38%
9
10
11
12
13
14
27%
<10%[c]
21%[d]
77%[e]
76%[e]
[a]
Unless otherwise stated, the reaction was conducted on
a 0.50 mmol scale [2 mol% Pd(OAc)2, 3 mol% ligand for
diphosphine ligand and 6 mol ligand for monophosphine
ligand, 0.50 mmol 1a, 0.50 mmol 2a, 1.5 mmol base] with
2.0 mL DMAc. Reaction temperature was 1208C. Reac-
tion time was 20 h.
Isolated yield.
Na2CO3 instead of Cs2CO3.
K2CO3 instead of Cs2CO3.
Figure 1. X-ray crystallography of product 3a.[16] Displace-
ment ellipsoids correspond to 30% probability.
the product was surprising, as it requires that the 1,3-
diketones are the key intermediates. In literature, Ta-
naka,[18a] and Beller,[18b] respectively, reported two
protocols for synthesizing enol esters from aryl ke-
[b]
[c]
[d]
[e]
tones
via
palladium-catalyzed
O-benzoylation
0.60 mmol 2a instead of 0.50 mmol 2a. Ad=adamantly,
dppm=1,1-bis(diphenylphosphino)methane, dppe=1,2-
bis(diphenylphosphino)ethane, dppp=1,3-bis(diphenyl-
(Scheme 3, a). Also, Beller[19b] and Skrydstrup[19a,c] in-
dependently reported two methods for accessing 1,3-
phosphino)propane, dppb=1,4-bis(diphenylphosphino)- diketones by palladium-catalyzed carbonylative a-ary-
butane,
dppf=1,1’-bis(diphenylphosphino)ferrocene,
lation of ketones (Scheme 3, b and c). However, the
carbonylative a-arylation of deoxybenzoin to give the
corresponding 1,3-diketones is still challenging and
has not been explored.
DPE=bis[(2-diphenylphosphino)phenyl] ether, xanth-
phos=4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene,
t-Bu=tert-butyl, DMAc=N,N-dimethylacetamide.
For the sake of clarifying the reaction intermediate
(DMAc) under CO pressure (Table 1, entries 1–10). and having a deeper insight into the reaction mecha-
Among the tested phosphine ligands, the best results nism, a set of control experiments was conducted.
were achieved with the bidentate phosphine dppp as Firstly no conversion of the substrate was found in
the ligand (Table 1, entry 3). When we attempted to the blank reaction without the palladium catalyst
replace cesium carbonate with cheaper and more (Scheme 4, a). Then in order to exclude the possibility
atom-economical alkali metal carbonates (Table 1, en- of Pd-catalyzed chlorocarbonylation of aryl bromide,
tries 11 and 12), no better yield was acquired. This 2-fluorobenzoyl chloride was employed to react with
effect may be due to the stronger basicity resulting deoxybenzoin under the optimized conditions
from the higher solubility of Cs2CO3 in DMAc,[16] (Scheme 4, b). Only a trace amount of the desired
which would thereby facilitate the transformation of product was observed on GC and no expected 1-(2-
deoxybenzoin to the nucleophilic enol species. An fluorophenyl)-2,3-diphenylpropane-1,3-dione was de-
excess amount of deoxybenzoin can further improve tected. For observing the reaction intermediate, some
the product yield (Table 1, entry 13). Remarkably, the measures were taken including reducing the base and
CO pressure can be reduced to 10 bar without any temperature to hinder the reaction process. When 1-
impact on the yield (Table 1, entry 14).
bromo-2-fluorobenzene was replaced with 1-fluoro-2-
Due to the equilibrium of deoxybenzoin between iodobenzene, a molecular ion peak at m/z=318.2 was
the enol and the ketone forms, palladium-catalyzed observed on GC-MS (Scheme 4, c). When the reac-
carbonylation can occur on either the oxygen of the tion temperature was further decreased to 608C, un-
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Palladium-Catalyzed Carbonylative Synthesis of 2,3-Disubstituted Chromones
Scheme 3. The synthesis of vinyl benzoates and 1,3-diketones via Pd-catalyzed carbonylations.
expectedly (Z)-1,2-diphenylvinyl 2-fluorobenzoate
With the help of the above discussed control ex-
was isolated in a 22% yield (Scheme 4, d). Moreover periment results, a plausible reaction mechanism was
3a was isolated in a 53% yield. Similar to the protocol proposed (Scheme 5). First 1a undergoes the oxida-
developed by Beller et al., the target product 3a and tive addition of Pd(0) to form an aryl-Pd(II) complex.
vinyl benzoate 9 can be obtained simultaneously in Then the aryl-Pd(II) complex goes through the CO
yields of 27% and 42%, respectively (Scheme 4, e). insertion and transmetallation with the Cs enolate of
At the same time, the other molecular ion peak at deoxybenzoin to generate the complex A.[20] After re-
m/z=318.2 was detected by GC-MS. This indicates ductive elimination of complex A, intermediate 9 is
the existence of a trace amount of diketone 8, which produced. With the promotion of base under heating
probably originates from 9. Vinyl benzoate 9 is able conditions, 9 is transformed to the 1,3-diketone inter-
to rearrange into the desired molecule 3a, as well as mediate 10 by a base-promoted Claisen–Hasse rear-
providing
a
small amount of deoxybenzoin rangement.[21] Through enolization and intramolecular
(Scheme 4, f). Without the presence of base, the ar- SNAr reaction under the basic condition,[22] 1,3-dike-
rangement of 9 did not proceed (Scheme 4, g). Be- tone 10 can be rapidly turned into 3a. Notably, the
cause the oxidative addition of aryl bromide to temperature required for the Claisen–Hasse rear-
a Pd(0) complex usually requires a much higher tem- rangement is between the temperature needed for the
perature than the oxidative addition of aryl iodide, activation of aryl iodides and aryl bromides.
the enol ester 9 generated from 1-bromo-2-fluoroben-
With the optimized conditions in hand, we focused
zene cannot be retained and it can further rearrange on evaluating the substrate scope of our method.
to the chromone 3a. That makes it impossible to ob- From the results of reactions between commercially
serve or isolate the enol ester intermediate from the available substituted 1-bromo-2-fluorobenzenes and
reaction of 1-bromo-2-fluorobenzene with deoxyben- deoxybenzoin (Table 2), our protocol is able to toler-
zoin by reducing the reaction temperature. However, ate the introduction of methyl groups (3b–d), a di-
in the reaction between 1-bromo-2-(trifluoromethyl)- fluoromethyl group (3i), fluorine atoms (3f–h) and
benzene and deoxybenzoin, we observed two molecu- chlorine atoms (3e) as substitutents on the benzene
lar ion peaks of m/z=368.1 by GC-MS, which proba- ring of 1-bromo-2-fluorobenzene. All of them can
bly are the vinyl benzoate 11 and 1,3-diketone 12 achieve moderate to good yields. Compared to 1-
(Scheme 4, h). This helps to indirectly prove that the bromo-2-fluorobenzenes with substituent groups at
reaction intermediate of 1-bromo-2-fluorobenzene is the 4- or 5-position, the substituent group at 3-posi-
also the enol ester 9.
tion has no significant impact on the yields (3d and
3h).
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Chaoren Shen et al.
Scheme 4. The control experiments.
The investigation of substituent effects on the 1-(4-chlorophenyl)-2-(pyridin-2-yl)ethan-1-one
may
deoxybenzoin (Table 3) reveals that the reaction also have formed a chelate structure with Pd.[23] The
is compatible to various substituent groups at differ- method is also not applicable to 1-(4-nitrophenyl)-2-
ent positions on both phenyl rings of deoxybenzoin. phenylethan-1-one (3x), which may be attributed to
For most of the substituted deoxybenzoins, moderate the complicated reactivity of the nitro group in Pd-
to good yields can be obtained (3j–v). However, no catalyzed carbonylations.
desired product was formed when deoxybenzoin was
Applying this methodology with substituted 1-
replaced with 1-(4-chlorophenyl)-2-(pyridin-2-yl)- bromo-2-fluorobenzenes and substituted 1,2-diaryl-
ethan-1-one (3w). It is inferred that the Cs enolate of ethan-1-ones, we can prepare 2,3-diphenylchromones
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Palladium-Catalyzed Carbonylative Synthesis of 2,3-Disubstituted Chromones
Table 3. Scope of substituted 1,2-diarylethan-1-ones.[a]
Product, Yield
3j, 63%
3k, 53%
3l, 55%
Scheme 5. A plausible reaction mechanism.
3m, 56%
3p, 56%
3n, 61%
3q, 57%
3o, 72%
3r, 67%
Table 2. Scope of substituted 1-bromo-2-fluorobenzenes.[a]
3s, 72%
3v, 51%
3t, 68%
3w, 0%
3u, 72%
3x, 0%
Product, Yield
3a, 74% (71%[b])
3b, 74%
3e, 64%
3h, 64%
3c, 76%
3f, 83%
3i, 61%
[a]
Unless otherwise stated, the reaction was conducted on
a 0.50 mmol scale [2 mol% Pd(OAc)2, 3 mol% dppp,
0.50 mmol 1a, 0.60 mmol 2, 1.5 mmol Cs2CO3] with
2.0 mL DMAc. Reaction temperature was 1208C. Reac-
tion time was 20 h. Yield of the isolated product.
3d, 69%
with substituted groups on both the backbone of the
chromone and the two benzene rings in moderate to
good yields as well (Table 4). It can efficiently broad-
en the access to chromones with more than one sub-
stituent group from readily available chemicals.
The methodology is also suitable for the reaction of
1,3-diphenylacetone with substituted 1-bromo-2-fluo-
robenzenes (Table 5).
3g, 79%
[a]
Unless otherwise stated, the reaction was conducted on
a 0.50 mmol scale [2 mol% Pd(OAc)2, 3 mol% dppp,
0.50 mmol 1, 0.60 mmol 2a, 1.5 mmol Cs2CO3] with
2.0 mL DMAc. Reaction temperature was 1208C. Reac-
tion time was 20 h. Yield of the isolated product.
0.50 mmol 1-fluoro-2-iodobenzene instead of 0.50 mmol
1a.
[b]
Furthermore, employing the methodology for the
controlled liberation of stoichiometric carbon monox-
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Chaoren Shen et al.
Table 4. Reaction of substituted 1-bromo-2-fluorobenzenes with Table 5. Reaction of substituted 1-bromo-2-fluorobenzenes
substituted 1,2-diarylethan-1-ones.[a] with 1,3-diphenylpropan-2-one.[a]
Product, Yield
Product, Yield
3y, 68%
3z, 58%
3aa, 60%
3ad, 63%
5a, 61%
5d, 52%
5b, 67%
5c, 63%
3ab, 58%
3ac, 74%
5e, 69%
[a]
Unless otherwise stated, the reaction was conducted on
a 0.50 mmol scale [2 mol% Pd(OAc)2, 3 mol% dppp,
0.50 mmol 1, 0.60 mmol 4, 1.5 mmol Cs2CO3] with 2.0 mL
DMAc. Reaction temperature was 1208C. Reaction time
was 20 h. Yield of the isolated product.
3ae, 77%
3af, 75%
[a]
Unless otherwise stated, the reaction was conducted on
0.50 mmol scale [2 mol% Pd(OAc)2, 3 mol% dppp,
a
0.50 mmol 1, 0.60 mmol 2, 1.5 mmol Cs2CO3] with 2.0 mL
DMAc. Reaction temperature was 1208C. Reaction time
was 20 h. Yield of the isolated product.
Conclusions
An unexpected and efficient palladium-catalyzed car-
bonylation/intramolecular SNAr reaction has been de-
ide generated from 13C-labelled 9-methylfluorene-9- veloped for accessing 2,3-disubstituted chromones. In
carbonyl chloride (13COgen) in a two-chamber reactor contrast to what was expected, our control experi-
(COware) and 13C-labelled deoxybenzoin, singly or ments revealed that the Pd-catalyzed carbonylative
doubly 13C-labelled 2,3-diphenyl-4H-chromen-4-ones arylation of deoxybenzoin generated an enol ester in-
are able to be readily prepared (Scheme 6).
stead of a 1,3-diketone. Then this carbonylation event
For further expanding the substrate scope, we at- was followed by the Claisen–Hasse rearrangement of
tempted to apply this protocol for the preparation of the enol ester and an intramolecular SNAr,reaction to
flavone with acetophenone and 1-bromo-2-fluoroben- generate the chromones. The reaction displays good
zene (for more details see: the Supporting Informa- tolerance to various substituent groups at different
tion, Table S1). However, the best result with only positons on the starting materials. With the method of
a 40% yield can be obtained when the solvent is stoichiometric carbon monoxide, this protocol also
switched from DMAc to acetophenone (Scheme 7). provides a simple pathway to obtain singly and
Similarly, no desired product was generated when di- doubly 13C-labelled 2,3-disubstituted chromones.
hydrochalcone instead of deoxybenzoin was employed
(Supporting Information, Table S2). This phenomen-
on can be rationalized by the pKa difference between
deoxybenzoin,[24b] 1,3-diphenylacetone,[24b] acetophe-
none,[24a] and dihydrochalcone. It affects the keto-enol
tautomerism of acetophenone and dihydrochalcone,
which makes the formation of the enol ester more
sluggish.
Experimental Section
General Information and Materials
Nuclear magnetic resonance spectra were recorded on
Bruker Avance 300, Bruker ARX 400 and Varian Mercury
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Scheme 6. Preparation of 13C-labelled 2,3-diphenyl-4H-chromen-4-one.
mercially available and were used without further purifica-
tion. Substituted deoxybenzoins were prepared from the cor-
responding 2-arylacetic acid and arene via Friedel–Crafts
acylation according to the literature method.[25]
Scheme 7. Synthesis of flavone from acetophenone and 1-
bromo-2-fluorobenzene.
Representative Procedure for the Synthesis of 2,3-
Diaryl-4H-chromen-4-ones
1
A glass vial (4 mL) equipped with a septum and a small can-
nula was charged with Pd(OAc)2 (2.0 mol%), dppp
(3.0 mol%), 1-bromo-2-fluorobenzene or 1-fluoro-2-iodo-
benzene (0.50 mmol), deoxybenzoin or 1,3-diphenylacetone
(0.60 mmol), Cs2CO3 (1.5 mmol) and a magnetic stirring bar.
The vial was purged with argon before DMAc (2.0 mL) was
injected using a syringe. The vial (or several vials) was
placed in an alloy plate, which was transferred into
a 300 mL autoclave of the 4560 series from Parr Instruments
under an argon atmosphere. After flushing the autoclave
three times with CO, a CO pressure of 10 bar was reached
at ambient temperature. Afterwards, the reaction was per-
formed for 20 h at 1208C. After the reaction was complete,
the autoclave was cooled with an ice-water mixture to room
temperature and the pressure was released carefully. The so-
lution was diluted with acetone and then silica gel was
added into the solution. After evaporation of the organic
solvent, the crude product was purified by column chroma-
tography using ethyl acetate/n-pentane.
400 spectrometers. All H NMR experiments are reported in
d units, parts per million (ppm), and were measured relative
to residual chloroform (7.26 ppm) in the deuterated solvent.
All 13C NMR spectra are reported in ppm relative to
deuterochloroform (77.0 ppm) and all were obtained with
1H decoupling. All coupling constants J are reported in Hz.
The following abbreviations are used to describe peak split-
ting patterns when appropriate: s=singlet, d=doublet, t=
triplet, dd=doublet of doublets, sext=sextet, spt=septet,
m=multiplet and br s=broad singlet. All measurements
were carried out at room temperature unless otherwise
stated. Electron impact (EI) mass spectra were recorded on
an AMD 402 mass spectrometer (70 eV). High resolution
mass spectra (HR-MS) were recorded on an Agilent 6210 or
an LC TOF (ES) apparatus. The data are given as mass
units per charge (m/z). Gas chromatography analysis was
performed on an Agilent HP-5890 instrument with an FID
detector and HP-5 capillary column (polydimethylsiloxane
with 5% phenyl groups, 30 m, 0.32 mm i.d., 0.25 mm film
thickness) using argon as carrier gas. The products were iso-
lated from the reaction mixture by column chromatography
on silica gel 60, 0.063–0.2 mm, 70–230 mesh (Merck).
DMAc (anhydrous, 99.8%) was purchased from Fluka and
used as received. 1-Bromo-2-fluorobenzene, 1-fluoro-2-iodo-
benzene, all of the substituted 1-fluoro-2-iodobenzenes, de-
oxybenzoin, 1,3-diphenylacetone, acetophenone were com-
2,3-Diphenyl-4H-chromen-4-one[26] (3a): white solid;
1H NMR (300 MHz, CDCl3): d=8.23 (dd, J=1.8, 8.0 Hz,
1H), 7.66–7.60 (m, 1H), 7.47 (dd, J=0.9, 8.4 Hz, 1H), 7.38–
7.13 (m, 11H); 13C NMR (75 MHz, CDCl3): d=177.4, 161.5,
156.1, 133.7, 133.3, 132.9, 131.2, 130.1, 129.6, 128.3, 128.1,
127.6, 126.4, 125.1, 123.5, 123.0, 118.0; IR (ATR): n=1634,
1559, 1464, 1375, 1294, 1224, 1144, 1049, 921, 871, 756, 695,
640, 575, 549, 507, 482 cmÀ1.
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Chaoren Shen et al.
7-Methyl-2,3-diphenyl-4H-chromen-4-one (3b): white
solid; 1H NMR (300 MHz, CDCl3): d=8.10 (d, J=8.1 Hz,
1H), 7.33–7.13 (m, 12H), 2.45 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=177.3, 161.2, 156.2, 145.0, 133.4, 133.0, 131.3,
130.0, 129.6, 128.2, 128.1, 127.6, 126.6, 126.2, 125.0, 122.9,
121.3, 117.7, 21.9; GC-MS (EI, 70 eV): m/z (%)=312 (39),
311 (100), 178 (24), 176 (18), 152 (12), 77 (16); HR-MS
(ESI): m/z=313.12268, calcd. for C22H17O2 [M+H]+:
313.12231; m/z=335.10479, calcd. for C22H16O2Na [M+H]+:
335.10425.
6-Methyl-2,3-diphenyl-4H-chromen-4-one (3c): white
solid, 1H NMR (300 MHz, CDCl3): d=8.0 (d, J=1.5 Hz,
1H), 7.46–7.13 (m, 12H), 2.42 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=177.4, 161.4, 154.4, 135.0, 135.0, 133.5, 133.1,
131.3, 130.0, 129.6, 128.3, 128.1, 127.6, 125.7, 123.2, 122.8,
117.8, 21.1; GC-MS (EI, 70 eV): m/z (%)=312 (41), 311
(100), 178 (27), 176 (17), 152 (9), 105 (11), 78 (15), 77 (14);
HR-MS (ESI): m/z=313.12258, calcd. for C22H17O2 [M+
H]+: 313.12231; m/z=335.10465, calcd. for C22H16O2Na [M+
Na]+: 335.10425.
8-Methyl-2,3-diphenyl-4H-chromen-4-one (3d): white
solid; 1H NMR (300 MHz, CDCl3): d=8.06 (dt, J=0.9,
8.1 Hz, 1H), 7.47 (d, J=7.2 Hz, 1H), 7.56–7.14 (m, 11H),
2.49 (s, 3H); 13C NMR (75 MHz, CDCl3): d=177.7, 161.0,
154.6, 134.5, 133.5, 133.0, 131.3, 130.1, 129.6, 128.3, 128.2,
127.6, 127.4, 124.7, 124.0, 123.4, 122.7, 15.7; GC-MS (EI,
70 eV): m/z (%)=312 (46), 311 (100), 178 (27); HRMS
(ESI): calcd for C22H17O2 [M+H]+ 313.12231, found
313.1229; calcd for C22H16NaO2 [M+Na]+ 335.10425, found
335.1043.
10.5 Hz), 128.25 (d, J=13.5 Hz), 127.78, 123.03, 120.41 (d,
J=3.0 Hz), 113.95 (d, J=22.5 Hz), 104.59 (d, J=25.5 Hz);
19F NMR (282 MHz, CDCl3): d=À102.68 (m); GC-MS (EI,
70 eV): m/z (%)=316 (47), 315 (100), 178 (22), 152 (6);
HR-MS (ESI): m/z=317.09741, calcd. for C21H14FO2 [M+
H]+: 317.09723; m/z=339.07948, calcd. for C21H13FO2Na
[M+Na]+: 339.07918.
8-Fluoro-2,3-diphenyl-4H-chromen-4-one
(3h):
white
solid; 1H NMR (300 MHz, CDCl3): d=7.97 (dt, J=8.0,
1.4 Hz, 1H), 7.44–7.10 (m, 12H); 13C NMR (75 MHz,
CDCl3): d=176.54 (d, J=3.0 Hz), 161.14, 152.92 (d, J=
251.3 Hz), 144.88 (d, J=11.3 Hz), 134.58, 131.14, 130.39,
129.70, 128.30 (d, J=16.5 Hz), 127.88, 125.44, 124.83, 124.77,
124.6 (d, J=6.0 Hz), 123.19, 121.37 (d, J=4.5 Hz), 119.32 (d,
J=16.5 Hz); 19F NMR (282 MHz, CDCl3): d=À133.5 (m);
GC-MS (EI, 70 eV): m/z (%)=316 (49), 315 (100), 178 (34),
152 (7); HR-MS (ESI): m/z=317.09791, calcd. for
C21H14FO2 [M+H]+: 317.09723; m/z=339.07963, calcd. for
C21H13NaFO2 [M+Na]+: 339.07918.
6-(Difluoromethyl)-2,3-diphenyl-4H-chromen-4-one (3i):
1
pale yellow solid; H NMR (300 MHz, CDCl3): d=8.34 (m,
1H), 7.81 (dd, J=8.9, 2.1 Hz, 1H), 7.57 (d, J=8.7 Hz, 1H),
7.35–7.13 (m, 10H), 6.70 (t, J=56.1 Hz, 1H); 13C NMR
(75 MHz, CDCl3): d=176.74, 161.83, 157.12, 132.87, 132.38,
131.35 (t, J=23.3 Hz), 131.13, 130.37 (d, J=4.5 Hz), 129.60,
128.41, 128.19, 127.89, 124.78 (t, J=6.8 Hz), 123.34, 119.11,
114.01 (t, J=237.8 Hz); 19F NMR (282 MHz, CDCl3): d=
À109.42 (d, J=84.6 Hz); GC-MS (EI, 70 eV): m/z (%)=348
(54.5), 347 (100), 178 (27), 152 (7); HR-MS (ESI): m/z=
349.10386, calcd. for C22H15F2O2 [M+H]+: 349.10346; m/z=
371.08616, calcd. for C22H14NaF2O2 [M+Na]+: 371.08541.
3-Phenyl-2-(p-tolyl)-4H-chromen-4-one (3j): white solid;
1H NMR (300 MHz, CDCl3): d=8.22 (ddd, J=0.6, 1.8,
8.0 Hz, 1H), 7.65–7.59 (m, 1H), 7.49 (dd, J=0.9, 8.3 Hz,
1H), 7.37–7.34 (m, 1H), 7.25–7.14 (m, 7H), 7.00 (d, J=
8.1 Hz, 1H), 2.25 (s, 3H); 13C NMR (75 MHz, CDCl3): d=
177.4, 161.6, 156.1, 140.5, 133.6, 133.1, 131.2, 130.4, 129.5,
128.8, 128.3, 127.6, 126.4, 125.0, 123.5, 122.6, 118.0, 21.5;
GC-MS (EI, 70 eV): m/z (%)=312 (48), 311 (86), 297 (100),
192 (29), 191 (29), 155 (15); HR-MS (ESI): m/z=313.1229,
calcd. for C22H17O2 [M+H]+: 313.12231; m/z=335.10419,
calcd. for C22H16NaO2 [M+Na]+: 335.10425; IR (ATR): n=
2914, 1631, 1607, 1563, 1459, 1376, 1295, 1217, 1182, 1145,
1109, 1048, 922, 872, 822, 760, 696, 615, 554, 500 cmÀ1.
6-Chloro-2,3-diphenyl-4H-chromen-4-one (3e): white
solid; 1H NMR (300 MHz, CDCl3): d=8.18 (dd, J=0.6,
1.2 Hz, 1H), 7.58 (dd, J=3.0, 4.5 Hz, 1H), 7.43 (dd, J=0.3,
4.5 Hz, 1H), 7.32–7.12 (m, 10H); 13C NMR (75 MHz,
CDCl3): d=176.2, 161.7, 154.4, 133.9, 132.9, 132.4, 131.1,
131.0, 130.3, 129.6, 128.4, 128.1, 127.8, 125.8, 124.5, 123.0,
119.8; GC-MS (EI, 70 eV): m/z (%)=334 (14), 333 (45), 332
(46), 331 (100), 178 (36), 176 (30), 163 (10), 152 (24), 126
(27), 98 (14), 77 (16), 63 (32); HR-MS (ESI): m/z=
333.0681, calcd. C21H1435ClO2 [M+H]+: 333.06768; m/z=
335.06592, calcd. for C21H1437ClO2 [M+H]+: 335.06552;
m/z=355.04996,
calcd
.C21H1335ClO2Na
[M+Na]+:
355.04963, m/z=357.04731, calcd. C21H1337ClO2Na [M+
Na]+: 357.04746.
6-Fluoro-2,3-diphenyl-4H-chromen-4-one
(3f):
white
2-(2,5-Dimethylphenyl)-3-phenyl-4H-chromen-4-one (3k):
light yellow solid; H NMR (300 MHz, CDCl3): d=8.25 (dd,
solid; 1H NMR (300 MHz, CDCl3): d=7.86 (dd, J=3.0,
4.1 Hz, 1H), 7.48 (dd, J=4.2, 4.5 Hz, 1H), 7.39–7.12 (m,
11H); 13C NMR (75 MHz, CDCl3): d=176.66 (d, J=
2.0 Hz), 161.81, 159.61 (d, J=245.0 Hz), 152.32 (d, J=
2.0 Hz), 133.06, 132.56, 131.20, 130.26, 129.58, 128.35, 128.16,
127.78, 124.70 (d, J=7.0 Hz), 122.37, 121.97 (d, J=26.0 Hz),
120.13 (d, J=8.0 Hz), 111.17 (d, J=23.0 Hz); 19F NMR
(282 MHz, CDCl3): d=À115.0 (m); GC-MS (EI, 70 eV):
m/z (%)=316 (42), 315 (100), 178 (28), 177 (11), 176 (20),
152 (11), 110 (17), 82 (16); HR-MS (ESI): m/z=317.09752,
calcd. for C21H14FO2 [M+H]+: 317.09723; m/z=339.07968,
calcd. for C21H13FO2Na [M+Na]+: 339.07918.
1
J=8.0, 1.7 Hz, 1H), 7.62 (ddd, J=8.6, 7.1, 1.7 Hz, 1H),
7.43–7.32 (m, 2H), 7.15–7.06 (m, 5H), 6.99–6.93 (m, 3H),
2.14 (s, 3H), 2.10 (s, 3H); 13C NMR (75 MHz, CDCl3): d=
177.1, 163.4, 156.2, 135.1, 133.6, 133.5, 132.9, 132.3, 130.8,
130.7, 130.5, 130.3, 127.8, 127.3, 126.4, 125.1, 124.3, 123.8,
118.0, 20.8, 19.3; GC-MS (EI, 70 eV): m/z (%)=326 (20),
325 (15), 312 (26), 311 (100), 206 (7), 191 (12); HR-MS
(EI): m/z=326.12995, calcd. for C23H18O2 [M]+: 326.13013.
2-Phenyl-3-(o-tolyl)-4H-chromen-4-one (3l): white solid;
1H NMR (300 MHz, CDCl3): d=8.22 (ddd, J=8.0, 1.7,
0.5 Hz, 1H), 7.65 (ddd, J=8.7, 7.1, 1.7 Hz, 1H), 7.49 (ddd,
J=8.4, 1.1, 0.5 Hz, 1H), 7.40–7.13 (m, 8H), 7.10–7.02 (m,
1H), 6.98–6.93 (m, 1H), 2.06 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=177.2, 161.1, 156.2, 137.7, 133.7, 133.2, 132.8,
131.2, 130.3, 130.2, 128.9, 128.2, 128.1, 126.4, 126.0, 125.1,
125.0, 123.4, 122.8, 118.0, 19.9; GC-MS (EI, 70 eV): m/z
7-Fluoro-2,3-diphenyl-4H-chromen-4-one
(3g):
white
solid; 1H NMR (300 MHz, CDCl3): d=8.23 (d, J=6.3,
9.0 Hz, 1H), 7.32–7.06 (m, 12H); 13C NMR (75 MHz,
CDCl3): d=176.52, 165.76 (d, J=252.8 Hz), 161.73, 157.12,
156.94, 132.93, 132.49, 131.16, 130.26, 129.54, 129.00 (d, J=
474
asc.wiley-vch.de
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2016, 358, 466 – 479

UPDATES
Palladium-Catalyzed Carbonylative Synthesis of 2,3-Disubstituted Chromones
(%)=313 (15), 312 (66), 311 (15), 295 (26), 235(50), 189
(20), 121 (100); HR-MS (ESI): m/z=313.12263, calcd. for
C22H17O2 [M+H]+: 313.12231; m/z=335.10464, calcd. for
C22H16O2Na [M+Na]+: 335.10425.
C21H1335Cl2O2
[M+H]+:
367.02871;
m/z=369.02649,
C21H1335Cl37ClO2 [M+H]+: 369.02617; m/z=371.02460,
calcd. for C21H1337Cl2O2 [M+H]+: 371.02428; m/z=
389.01107, calcd. for C21H1235Cl2O2Na [M+Na]+: 389.01066;
m/z=391.00845, calcd. for C21H1235Cl37ClO2Na [M+Na]+:
391.00811; m/z=393.00655, calcd. for C21H1237Cl2O2Na [M+
Na]+: 393.00622.
2-(4-Cyclohexylphenyl)-3-phenyl-4H-chromen-4-one
(3m): pale yellow solid; 1H NMR (300 MHz, CDCl3): d=
8.22 (dd, J=1.8, 8.0 Hz, 1H), 7.62 (ddd, J=8.7, 7.1, 1.7 Hz,
1H), 7.35 (ddd, J=8.1, 7.1, 1.1 Hz, 1H), 7.47–7.32 (m, 1H),
7.26–7.15 (m, 7H), 7.03 (d, J=8.3 Hz, 1H), 2.40 (tt, J=8.6,
3.4 Hz, 1H), 1.79–1.64 (m, 5H), 1.34–1.28 (5H); 13C NMR
(75 MHz, CDCl3): d=177.4, 161.6, 156.1, 150.5, 133.6, 133.1,
131.2, 130.6, 129.6, 128.3, 127.5, 126.6, 126.4, 125.0, 123.5,
122.6, 117.9, 44.4, 34.1, 26.7, 26.1; GC-MS (EI, 70 eV): m/z
(%)=380 (23), 297 (100), 202 (8); HR-MS (ESI): m/z=
381.18540, calcd. for C27H25O2 [M+H]+: 381.18491; m/z=
403.16735, calcd. for C27H24O2Na [M+Na]+: 403.16685.
2,3-Bis(4-chlorophenyl)-4H-chromen-4-one (3r): white
solid; 1H NMR (300 MHz, CDCl3): d=8.20 (dd, J=8.0,
1.7 Hz, 1H), 7.65 (ddd, J=8.7, 7.1, 1.7 Hz, 1H), 7.48–7.44
(m, 1H), 7.37 (ddd, J=8.1, 7.1, 1.1 Hz, 2H), 7.28–7.18 (m,
5H), 7.11–7.05 (m, 2H); 13C NMR (75 MHz, CDCl3): d=
177.0, 160.4, 156.0, 136.6, 134.0, 133.9, 132.6, 131.4, 131.1,
130.9, 128.8, 128.7, 126.4, 125.4, 123.3, 122.0, 118.0; GC-MS
(EI, 70 eV): m/z (%)=369 (18), 368 (36), 367 (75), 366 (53),
365 (100), 333 (15), 332 (14), 331 (47), 330 (11), 248 (23),
246 (37), 176 (39), 147 (13), 92 (12); HR-MS (ESI): m/z=
367.02877, calcd. for C12H1335Cl2O2 [M+H]+: 367.02871;
m/z=369.02642, calcd. for C12H1335Cl37ClO2 [M+H]+:
369.02617; m/z=389.01079, calcd. for C12H1235Cl2O2Na [M+
2-(4-Methoxyphenyl)-3-phenyl-4H-chromen-4-one
(3n):
1
white solid; H NMR (400 MHz, CDCl3): d=8.21 (dd, J=
2.0, 8.0 Hz, 1H), 7.64–7.60 (m, 1H), 7.47–7.45 (m, 1H),
7.36–7.32 (m, 1H), 7.30–7.16 (m, 7H), 6.72–6.69 (m, 2H),
3.72 (s, 3H); 13C NMR (100 MHz, CDCl3): d=177.4, 161.3,
160.9, 156.0, 133.5, 133.3, 131.3, 131.2, 128.4, 127.5, 126.4,
125.5, 125.0, 123.5, 122.1, 117.9, 113.5, 55.3; GC-MS (EI,
70 eV): m/z (%)=331 (100), 297 (42), 212 (36), 176 (31),
134 (14); HR-MS (ESI): m/z=329.11755, calcd. for
C22H17O3 [M+H]+: 329.11722; m/z=351.09928, calcd. for
C22H16O3 [M+Na]+: 351.09917.
Na]+:
C12H1235Cl37ClO2Na [M+Na]+: 391.00811.
3-(4-Chlorophenyl)-2-phenyl-4H-chromen-4-one
389.01066;
m/z=391.00825,
calcd.
for
(3s):
1
white solid; H NMR (300 MHz, CDCl3): d=8.34 (dd, J=
8.0, 1.7 Hz, 1H), 7.76 (ddd, J=8.7, 7.2, 1.7 Hz, 1H), 7.62–
7.57 (m, 1H), 7.53–7.28 (m, 8H), 7.25–7.19 (m, 2H);
13C NMR (75 MHz, CDCl3): d=177.1, 161.8, 156.1, 133.9,
133.6, 133.0, 132.7, 131.4, 130.4, 129.6, 128.6, 128.3, 126.4,
125.3, 123.4, 121.8, 118.0; GC-MS (EI, 70 eV): m/z (%)=
334 (16), 333 (40), 332 (47), 331 (100), 295 (9), 212 (26), 176
(22), 151 (7), 134 (7); HR-MS (ESI): m/z=333.06823, calcd.
for C21H1435ClO2 [M+H]+: 333.06768; m/z=335.06583,
calcd. for C21H1437ClO2 +H]+: 335.06552; m/z=355.05019,
calcd. for C21H1335ClO2Na [M+Na]+: 355.04963; m/z=
357.04782, calcd. for C21H1337ClO2Na [M+Na]+: 357.04746.
2,3-Bis(4-methoxyphenyl)-4H-chromen-4-one (3o): white
solid; 1H NMR (300 MHz, CDCl3): d=8.19 (dd, J=8.0,
1.7 Hz, 1H), 7.61 (ddd, J=8.6, 7.1, 1.7 Hz, 1H), 7.45 (dd,
J=8.5, 1.1 Hz, 1H), 7.37–7.27 (m, 3H), 7.11–7.05 (m, 2H),
6.82–6.69 (m, 4H), 3.74 (s, 3H), 3.73 (s, 3H), 2.28 (s, 3H);
13C NMR (75 MHz, CDCl3): d=177.6, 170.7, 161.2, 160.8,
158.9, 155.9, 133.5, 132.3, 131.2, 126.3, 125.6, 125.3, 124.9,
123.4, 121.5, 117.9, 113.9, 113.5, 55.3, 55.2, 21.6; GC-MS (EI,
70 eV): m/z (%)=359 (22), 358 (100), 357 (95), 343 (23),
327 (28), 238 (18), 223 (29), 195 (11), 152 (14), 92(7); HR-
MS (ESI): m/z=359.12802, calcd. for C23H19O4 [M+H]+:
359.12779; m/z=381.10982, calcd. for C23H18O4Na [M+
Na]+: 381.10973.
3-(4-Chlorophenyl)-2-(p-tolyl)-4H-chromen-4-one
(3t):
1
white solid; H NMR (300 MHz, CDCl3): d=8.20 (dd, J=
8.0, 1.7 Hz, 1H), 7.62 (tt, J=7.3, 1.0 Hz, 1H), 7.47–7.43 (m,
1H), 7.35 (ddt, J=7.9, 7.1, 0.8 Hz, 1H), 7.23–7.18 (m, 4H),
7.11–7.00 (m, 4H), 2.27 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=177.1, 161.9, 156.0, 140.8, 133.8, 133.5, 132.6,
131.6, 130.1, 129.5, 129.0, 128.5, 126.3, 125.2, 123.4, 121.4,
118.0, 21.5; GC-MS (EI, 70 eV): m/z (%)=348 (20), 347
(37), 346 (58), 345 (80), 333 (34), 332 (23), 331 (100), 309
(9), 226 (27), 189 (34), 172 (8); HR-MS (ESI): m/z=
347.08366, calcd. for C22H1635ClO2 [M+H]+: 347.08333;
m/z=349.08147, calcd. for C22H1637ClO2 [M+H]+:
349.08123; m/z=369.06572, calcd. for C22H1535ClO2Na [M+
Na]+: 369.06528; m/z=371.06360, calcd. for C22H1537ClO2Na
[M+Na]+: 371.06317.
2-(4-Chlorophenyl)-3-phenyl-4H-chromen-4-one
(3p):
1
white solid; H NMR (300 MHz, CDCl3): d=8.22 (ddd, J=
0.6, 1.8, 7.9 Hz, 1H), 7.68–7.62 (m, 1H), (ddd, J=0.6, 1.2,
8.5 Hz, 1H), 7.40–7.35 (m, 1H), 7.29–7.13 (m, 9H);
13C NMR (75 MHz, CDCl3): d=177.2, 160.0, 156.0, 136.3,
133.9, 132.6, 131.7, 131.1, 130.9, 128.5, 128.5, 127.9, 126.5,
125.3, 123.5, 123.1, 118.0; GC-MS (EI, 70 eV): m/z (%)=
328 (66), 327 (100), 313 (22), 284 (11), 255 (6), 208 (26), 193
(22), 165 (31); HR-MS (ESI): m/z=333.06822, calcd. for
C21H1435ClO2 [M+H]+: 333.06768; m/z=335.0658, calcd. for
C21H1437ClO2 [M+H]+: 335.06552; m/z=355.0503, calcd. for
C21H13Na35ClO2 [M+Na]+: 355.04963; m/z=357.04777,
calcd. for C21H13Na37ClO2 [M+Na]+: 357.04746.
3-(4-Chlorophenyl)-2-(4-cyclohexylphenyl)-4H-chromen-
4-one (3u): white solid; 1H NMR (300 MHz, CDCl3): d=
8.22 (dd, J=8.0, 1.7 Hz, 1H), 7.64 (ddd, J=8.7, 7.1, 1.7 Hz,
1H), 7.48 (dd, J=8.5, 1.1 Hz, 1H), 7.39–7.33 (m, 2H), 7.30–
7.25 (m, 2H), 7.24–7.10 (m, 2H), 7.08–7.01 (m, 3H), 2.40
(qt, J=5.8, 2.7 Hz, 1H), 1.81–1.61 (m, 5H), 1.38–1.10 (m,
5H); 13C NMR (75 MHz, CDCl3): d=176.6, 162.1, 156.2,
150.8, 135.3, 133.7, 133.00, 132.6, 130.3, 129.6, 129.4, 128.8,
126.9, 126.7, 126.4, 125.1, 123.3, 120.8, 118.0, 44.4, 34.1, 34.1,
26.7, 26.0; GC-MS (EI, 70 eV): m/z (%)=380 (29), 379
(100), 335 (6), 310 (7); HR-MS (EI): m/z=415.14611, calcd.
for C27H2435ClO2 [M+H]+: 415.14593; m/z=417.14429,
3-(2,4-Dichlorophenyl)-2-phenyl-4H-chromen-4-one (3q):
1
white solid; H NMR (300 MHz, CDCl3): d=8.30 (dd, J=
8.0, 1.7 Hz, 1H), 7.74 (ddd, J=8.7, 7.1, 1.7 Hz, 1H), 7.59–
7.55 (m, 1H), 7.49–7.29 (m, 7H), 7.19 (dd, J=8.3, 2.1 Hz,
1H), 7.08 (d, J=8.2 Hz, 1H); 13C NMR (75 MHz, CDCl3):
d=176.4, 162.4, 156.2, 136.0, 134.7, 134.0, 133.5, 132.7, 131.4,
130.6, 129.6, 128.8, 128.4, 127.4, 126.4, 125.4, 123.2, 120.3,
118.1; GC-MS (EI, 70 eV): m/z (%)=333 (37), 332 (24), 331
(100), 239 (6), 176 (11); HR-MS (ESI): m/z= calcd. for
Adv. Synth. Catal. 2016, 358, 466 – 479
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
475

UPDATES
Chaoren Shen et al.
calcd. for C27H2437ClO2 [M+H]+: 417.14418; m/z=
437.12820, calcd. for C27H2335ClO2Na [M+Na]+: 437.12788;
m/z=439.12623, calcd. for C27H2337ClO2Na [M+Na]+:
439.12613.
2-(4-Chlorophenyl)-6-fluoro-3-phenyl-4H-chromen-4-one
(3ac): white solid; H NMR (300 MHz, CDCl3): d=7.85 (dd,
1
J=8.2, 3.0 Hz, 1H), 7.47 (dd, J=9.1, 4.2 Hz, 1H), 7.37 (ddd,
J=9.1, 7.6, 3.1 Hz, 1H), 7.28–7.23 (m, 4H), 7.20–7.10 (m,
5H); 13C NMR (75 MHz, CDCl3): d=176.50 (d, J=2.5 Hz),
160.43, 159.63 (d, J=245.3 Hz) 152.19 (d, J=1.5 Hz), 136.47,
132.23, 131.43, 131.06, 130.87, 128.53, 128.49, 128.00, 124.62
(d, J=7.5 Hz) 122.49, 122.08 (d, J=25.5 Hz), 120.06 (d, J=
8.3 Hz), 111.19 (d, J=24.0 Hz); 19F NMR (282 MHz,
CDCl3): d=À114.7 (m); GC-MS (EI, 70 eV): m/z (%)=352
(16), 351 (40), 350 (49), 349 (100), 315 (54), 212 (40), 176
(24), 143 (11); HR-MS (ESI): m/z=351.05851, calcd. for
C21H1335ClFO2 [M+H]+: 351.05826; m/z=353.05643, calcd.
for C21H1337ClFO2 [M+H]+: 353.05609; m/z=373.04055,
calcd, for C21H12Na35ClFO2 [M+Na]+: 373.04021; m/z=
375.03843, calcd. for C21H12Na37ClFO2 [M+Na]+: 375.03804.
6-Fluoro-2-(4-methoxyphenyl)-3-phenyl-4H-chromen-4-
3-(2-Chlorophenyl)-2-phenyl-4H-chromen-4-one
(3v):
1
white solid; H NMR (300 MHz, CDCl3): d=8.23 (dd, J=
8.0, 1.7 Hz, 1H), 7.65 (ddd, J=8.6, 7.1, 1.7 Hz, 1H), 7.49
(dd, J=8.5, 1.1 Hz, 1H), 7.40–7.16 (m, 8H), 7.15–7.04 (m,
2H); 13C NMR (75 MHz, CDCl3): d=176.6, 162.1, 156.2,
135.2, 133.9, 133.0, 132.7, 132.7, 130.4, 129.7, 129.5, 128.8,
128.2, 126.9, 126.5, 125.3, 123.3, 121.3, 118.1; GC-MS (EI,
70 eV): m/z (%)=298 (21), 297 (100), 268 (2), 239 (5), 176
(8), 134 (4); HR-MS (ESI): m/z=333.06798, calcd. for
C21H1435ClO2 [M+H]+: 333.06768; m/z=335.06579, calcd.
for C21H1437ClO2 [M+H]+: 335.06552; m/z=355.05006,
calcd. for C21H1435ClO2Na [M+Na]+: 355.04963; m/z=
357.04774, calcd. for C21H1437ClO2Na [M+Na]+: 357.04746.
1
6-Methyl-3-phenyl-2-(p-tolyl)-4H-chromen-4-one
(3y):
one (3ad): white solid; H NMR (400 MHz, CDCl3): d=7.83
1
white solid; H NMR (300 MHz, CDCl3): d=7.99 (dd, J=
1.5, 0.7 Hz, 1H), 7.45–7.32 (m, 2H), 7.27–7.12 (m, 7H), 7.01-
6.96 (m, 2H), 2.40 (s, 3H), 2.25 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=177.4, 161.5, 154.3, 140.3, 134.9, 134.8, 133.3,
131.3, 130.5, 129.5, 128.8, 128.3, 127.5, 125.6, 123.2, 122.4,
117.7, 21.4, 21.0; GC-MS (EI, 70 eV): m/z (%)=327 (10),
326 (53), 325 (99), 311 (100), 192 (36), 162 (14); HR-MS
(ESI): m/z=327.13848, calcd. for C23H19O2 [M+H]+:
327.13796; m/z=349.12019, calcd. for C23H18O2Na [M+
Na]+: 349.11990.
(dd, J=8.3, 3.1 Hz, 1H), 7.46 (dd, J=9.1, 4.2 Hz, 1H), 7.34
(ddd, J=9.1, 7.7, 3.1 Hz, 1H), 7.29–7.22 (m, 5H), 7.17–7.13
(m, 2H), 6.72–6.68 (m, 2H), 3.72 (s, 3H); 19F NMR
(282 MHz, CDCl3): d=À115.3 (m); 13C NMR (100 MHz,
CDCl3): d=176.64 (d, J=2.0 Hz), 161.63, 161.06, 159.54 (d,
J=245.0 Hz), 152.22 (d, J=2.0 Hz), 133.02, 131.28, 131.17,
128.45, 127.67, 125.17, 124.66 (d, J=7.0 Hz), 121.77 (d, J=
26.0 Hz), 121.46, 119.98 (d, J=8.0 Hz), 113.59, 111.13 (d, J=
23.0 Hz), 55.35; GC-MS (EI, 70 eV): m/z (%)=347 (15),
346 (76), 345 (100), 331 (21), 315 (46), 208 (30), 193 (22),
165 (30), 139 (7); HR-MS (ESI): m/z=347.10808, calcd. for
C22H16FO3 [M+H]+; 347.10780; m/z=369.08993, calcd. for
C22H15FO3Na [M+Na]+: 369.08974.
2-(4-Methoxyphenyl)-6-methyl-3-phenyl-4H-chromen-4-
one (3ae): white solid; 1H NMR (300 MHz, CDCl3): d=
7.99–7.96 (m, 1H), 7.44–7.27 (m, 4H), 7.11–7.05 (m, 2H),
6.83–6.69 (m, 4H), 3.74 (s, 3H), 2.40 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=177.4, 161.3, 160.9, 156.0, 133.5, 133.3,
131.3, 131.2, 128.4, 127.5, 126.4, 125.5, 125.0, 123.5, 122.1,
117.9, 113.5, 55.3, 21.6; GC-MS (EI, 70 eV): m/z (%)=343
(13), 342 (66), 341 (100), 327 (23), 311 (26), 208 (19), 193
(17), 165 (27), 139 (7); HR-MS (ESI): m/z=343.13287,
calcd. for C23H19O3 [M+H]+: 343.13287; m/z=365.11514,
calcd. for C23H18O3Na [M+Na]+: 365.11482.
7-Methyl-3-phenyl-2-(p-tolyl)-4H-chromen-4-one
(3z):
1H NMR (400 MHz, CDCl3): d=8.22 (d, J=8.0 Hz, 1H),
7.39–7.27 (m, 9H), 7.12 (d, J=8.4 Hz, 2H), 2.57 (s, 3H),
2.38 (s, 3H); 13C NMR (100 MHz, CDCl3): d=177.3, 161.3,
156.2, 144.9, 140.3, 133.3, 131.3, 130.5, 129.5, 128.8, 128.3,
127.5, 126.6, 126.1, 122.5, 121.3, 117.7, 21.9, 21.5; GC-MS
(EI, 70 eV): m/z (%)=326 (48), 325 (100), 311 (87), 192
(28), 191 (23), 162 (12); HR-MS (ESI): m/z=327.13823,
calcd. for C23H19O2 [M+H]+: 327.13796; m/z=349.12016,
calcd. for C23H18O2Na [M+Na]+: 349.11990.
2-(4-Chlorophenyl)-7-methyl-3-phenyl-4H-chromen-4-one
1
(3aa): white solid; H NMR (300 MHz, CDCl3): d=8.09 (d,
J=8.1 Hz, 1H), 7.27–7.21 (m, 5H), 7.19–7.11 (m, 6H), 2.45
(s, 3H); 13C NMR (75 MHz, CDCl3): d=177.1, 159.8, 156.1,
145.2, 136.1, 132.7, 131.8, 131.1, 130.9, 128.4, 128.4, 127.8,
126.8, 126.2, 123.0, 121.2, 117.6, 21.9; GC-MS (EI, 70 eV):
m/z (%)=347 (40), 346 (44), 345 (100), 311 (28), 212 (29),
176 (23), 151 (8), 78 (7); HR-MS (ESI): m/z=347.08355,
calcd. for C22H1635ClO2 [M+H]+: 347.0833; m/z=349.08146,
calcd. for C22H1637ClO2 [M+H]+: 349.08123.
2,3-Bis(4-methoxyphenyl)-6-methyl-4H-chromen-4-one
1
(3af): white solid; H NMR (300 MHz, CDCl3): d=7.99–7.96
(m, 1H), 7.44–7.27 (m, 4H), 7.11–7.05 (m, 2H), 6.83–6.69
(m, 4H), 3.74 (s, 3H), 3.73 (s, 3H), 2.40 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=177.7, 170.8, 161.0, 160.7, 158.9, 154.2,
134.8, 132.4, 131.2, 125.8, 125.6, 124.5, 123.1, 121.4, 117.6,
113.9, 113.5, 55.3, 55.2, 21.6; GC-MS (EI, 70 eV): m/z (%)=
372 (92), 371 (100), 357 (23), 341 (21), 223 (31), 195 (10),
152 (12); HR-MS (ESI): m/z=373.14405, calcd. for
C24H21O4 [M+H]+: 373.14344; m/z=395.12592, calcd. for
C24H20O4Na [M+Na]+: 395.12538.
2-Benzyl-3-phenyl-4H-chromen-4-one (5a): white solid;
1H NMR (300 MHz, CDCl3): d=8.14 (ddd, J=8.0, 1.8,
0.5 Hz, 1H), 7.55 (ddd, J=8.6, 7.1, 1.7 Hz, 1H), 7.40–7.26
(m, 5H), 7.24–7.14 (m, 5H), 7.12–7.06 (m, 2H), 3.83 (s,
2H); 13C NMR (75 MHz, CDCl3): d=177.2, 164.0, 156.0,
136.2, 133.5, 132.8, 130.6, 128.8, 128.7, 128.6, 128.0, 127.0,
126.3, 124.9, 124.2, 123.5, 117.8, 38.6; GC-MS (EI, 70 eV):
m/z (%)=31 (21), 312 (100), 297 (25), 191 (19), 165 (11),
121 (30), 92 (7); HR-MS (ESI): m/z=313.12286, calcd. for
6-Chloro-2-(4-chlorophenyl)-3-phenyl-4H-chromen-4-one
1
(3ab): white solid, H NMR (300 MHz, CDCl3): d=8.17 (d,
J=2.6 Hz, 1H), 7.58 (dd, J=8.9, 2.6 Hz, 1H), 7.42 (d, J=
8.9 Hz, 1H), 7.29–7.21 (m, 4H), 7.21–7.08 (m, 5H);
13C NMR (75 MHz, CDCl3): d=176.1, 160.4, 154.3, 136.5,
134.1, 132.2, 131.3, 131.2, 131.0, 130.9, 128.6, 128.5, 128.1,
125.8, 124.4, 123.1, 119.7; GC-MS (EI, 70 eV): m/z (%)=
367 (73), 366 (53), 365 (100), 331 (58), 239 (12), 212 (58),
176 (37), 151 (26), 119 (14); HR-MS (ESI): m/z=367.02866,
calcd. for C21H1335Cl2O2 [M+H]+: 367.02871; m/z=
369.02712, calcd. for C21H1337Cl2O2 [M+H]+: 369.02617;
m/z=389.01073, calcd. for C21H1235Cl2O2Na [M+Na]+:
389.01066; m/z=391.00803, calcd. for C21H1237Cl2O2Na [M+
Na]+: 391.00811.
476
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Adv. Synth. Catal. 2016, 358, 466 – 479

UPDATES
Palladium-Catalyzed Carbonylative Synthesis of 2,3-Disubstituted Chromones
C22H17O2 [M+H]+: 313.12231; m/z=335.10488, calcd. for
C22H16O2Na [M+Na]+: 335.10425.
(m); GC-MS (EI, 70 eV): m/z (%)=318 (16), 165 (21), 152
(11), 123 (100), 105 (15), 95 (29), 90 (8), 75 (12); HR-MS
(EI): m/z=318.10541, calcd. for C21H15O2F: 318.10506.
2-Benzyl-7-methyl-3-phenyl-4H-chromen-4-one
(5b):
white solid; 1H NMR (300 MHz, CDCl3): d=8.02 (d, J=
8.1 Hz, 1H), 7.40–7.30 (m, 3H), 7.23–7.06 (m, 9H), 3.81 (s,
2H), 2.38 (s, 3H); 13C NMR (75 MHz, CDCl3): d=177.1,
163.6, 156.1, 144.7, 136.3, 133.0, 130.6, 128.7, 128.7, 128.5,
127.9, 127.0, 126.4, 126.0, 124.1, 121.2, 117.6, 38.6, 21.8; GC-
MS (EI, 70 eV): m/z (%)=327 (21), 326 (99), 325 (100), 311
(25), 191 (14), 189 (14), 135 (27); HR-MS (EI): m/z=
327.13838, calcd. for C23H19O2 [M+H]+: 327.13796; m/z=
349.12019, calcd. for C23H18O2Na [M+Na]+: 349.11990.
General Procedure for the Synthesis of 4-13C-2,3-
diphenyl-4H-chromen-4-one
In a glove-box under argon, a 20.0-mL two-chamber system
(COware) was loaded. To chamber A of the two-chamber
system were added in the following order Pd(cod)Cl2
(1.9 mg, 0.0075 mmol, 1.0 mol%), HBF4P(t-Bu)3 (2.0 mg,
0.0075 mmol, 1.0 mol%), 13COgen (182 mg, 0.75 mmol,
1.0 equiv.), DMAc (2.0 mL) and Cy2NMe (320 mL, 1.5 mmol,
2.0 equiv.) and a magnetic stirring bar. To chamber B of the
two-chamber system were added in the following order
Pd(OAc)2 (2.3 mg, 0.01 mmol, 2.0 mol%), dppp (6.3 mg,
0.015 mmol, 3.0 mol%), 1-bromo-2-fluorobenzene (87.5 mg,
0.5 mmol, 1.0 equiv.), deoxybenzoin (117.8 mg, 0.6 mmol,
1.2 equiv.), Cs2CO3 (488 mg, 1.5 mmol, 3.0 equiv.) and a mag-
netic stirring bar, followed by DMAc (2.0 mL).
Both chambers were sealed using a screw cap and
a Teflonꢁ coated silicone seal. The two chamber system was
removed from the glove-box and settled in a pre-heated oil
bath at 1208C for 20 h. Then the two-chamber system was
opened to air and the reaction mixture in chamber B was di-
luted with acetone and then silica gel was added into the so-
lution. After evaporation of the organic solvent, the crude
product was purified by column chromatography using ethyl
acetate/n-pentane 1:10 as eluent.
2-Benzyl-6-methyl-3-phenyl-4H-chromen-4-one
(5c):
1
white solid; H NMR (300 MHz, CDCl3): d=7.94–7.91 (m,
1H), 7.35 (dddd, J=12.0, 7.0, 5.5, 3.8 Hz, 4H), 7.24–7.14 (m,
6H), 7.08 (ddd, J=7.8, 1.7, 0.8 Hz, 2H), 3.82 (s, 2H), 2.36
(s, 3H); 13C NMR (75 MHz, CDCl3): d=177.2, 163.8, 154.3,
136.3, 134.8, 134.7, 133.0, 130.6, 128.7, 128.7, 128.5, 128.0,
127.0, 125.5, 124.1, 123.1, 117.6, 38.6, 21.0; GC-MS (EI,
70 eV): m/z (%)=327 (22), 326 (100), 325 (96), 311 (23),
191 (13), 189 (13), 165 (7), 135 (30); HR-MS (ESI): m/z=
327.13838, calcd. for C23H19O2 [M+H]+: 327.13796; m/z=
349.12046, calcd. for C23H18O2Na [M+Na]+: 349.11990.
2-Benzyl-8-methyl-3-phenyl-4H-chromen-4-one
(5d):
1
white solid; H NMR (300 MHz, CDCl3): d=8.02–7.96 (m,
1H), 7.43–7.32 (m, 4H), 7.26–7.11 (m, 8H), 3.85 (s, 2H),
2.34 (s, 3H); 13C NMR (75 MHz, CDCl3): d=177.6, 163.6,
154.5, 136.2, 134.3, 133.0, 130.7, 129.0, 128.7, 128.6, 128.0,
127.2, 127.1, 124.5, 123.9, 123.8, 123.3, 38.8, 15.6; GC-MS
(EI, 70 eV): m/z (%)=327 (21), 326 (100), 325 (93), 311
(22), 191 (13,)189 (13), 135 (30), 106 (8); HR-MS (EI):
m/z=327.13856, calcd. for C23H19O2 [M+H]+: 327.13796;
m/z=349.11974, calcd. for C23H18O2Na [M+Na]+:
349.11990.
4-13C-2,3-Diphenyl-4H-chromen-4-one (3a1): white solid;
1H NMR (400 MHz, CDCl3): d=8.27 (dd, J=8.0, 1.6 Hz,
1H), 7.67 (dt, J=7.6, 1.6 Hz, 1H), 7.50 (d, J=8.4 Hz, 1H),
7.41–7.19 (m, 11H); 13C NMR (100 MHz, CDCl3): d=177.3
(13C-enriched), 161.5, 156.1, 133.7, 133.3, 132.9, 131.3, 130.1,
129.6, 128.3, 128.1, 127.6, 126.4, 125.1 (d, J=3.4 Hz), 123.5
(d, J=55 Hz), 123.0 (d, J=55 Hz), 118.0 (d, J=1.7 Hz);
HR-MS (ESI): m/z=300.1107, calcd. for C2013CH15O2 [M+
H]+: 300.1106.
2-Benzyl-6-fluoro-3-phenyl-4H-chromen-4-one (5e): white
solid, 1H NMR (300 MHz, CDCl3): d=7.78 (dd, J=8.3,
3.0 Hz, 1H), 7.41–7.16 (m, 10H), 7.08 (dd, J=7.8, 1.7 Hz,
2H), 3.83 (s, 2H); 13C NMR (75 MHz, CDCl3): d=176.52,
164.32, 159.49 (d, J=244.5 Hz), 152.26, 136.01, 132.52,
130.54, 128.81, 128.76, 128.64, 128.20, 127.13, 124.61 (d, J=
7.1 Hz), 123.65, 121.72 (d, J=25.5 Hz), 119.96 (d, J=
7.5 Hz), 111.06 (d, J=23.3 Hz), 38.61; 19F NMR (282 MHz,
CDCl3): d=À115.2 (m); GC-MS (EI, 70 eV): m/z (%)=330
(100), 329 (92), 315 (28), 191 (32), 165 (8), 139 (21); HR-MS
(EI): m/z=330.10423, calcd. for C22H15O2F: 330.10506.
General Procedure for the Synthesis of 2,4-13C2-2,3-
Diphenyl-4H-chromen-4-one
In a glove-box under argon, a 20.0-mL two-chamber system
(COware) was loaded. To chamber A of the two-chamber
system were added in the following order Pd(cod)Cl2
(1.5 mg, 0.006 mmol, 1.0 mol%), HBF4P(t-Bu)3 (1.6 mg,
0.006 mmol, 1.0 mol%), 13COgen (145 mg, 0.6 mmol,
1.0 equiv.), DMAc (2.0 mL) and Cy2NMe (256 mL, 1.2 mmol,
2.0 equiv.) and a magnetic stirring bar. To chamber B of the
two-chamber system were added in the following order
Pd(OAc)2 (1.8 mg, 0.008 mmol, 2.0 mol%), dppp (4.9 mg,
0.012 mmol, 3.0 mol%), 1-bromo-2-fluorobenzene (70.0 mg,
0.4 mmol, 1.0 equiv.), 13C-labelled deoxybenzoin (94.0 mg,
0.48 mmol, 1.2 equiv.),[27] Cs2CO3 (390 mg, 1.2 mmol,
3.0 equiv.) and a magnetic stirring bar, followed by DMAc
(2.0 mL).
Both chambers were sealed using a screw cap and
a Teflonꢁ coated silicone seal. The two chamber system was
removed from the glove-box and settled in a pre-heated oil
bath at 1208C for 20 h. Afterwards the two-chamber system
was opened to air and the reaction mixture in chamber B
was diluted with acetone and then silica gel was added into
1
2-Phenyl-4H-chromen-4-one[13a] (6): white solid; H NMR
(300 MHz, CDCl3): d=8.24 (dd, J=8.0, 1.7 Hz, 1H), 7.97–
7.90 (m, 2H), 7.71 (ddd, J=8.6, 7.1, 1.7 Hz, 1H), 7.60–7.49
(m, 4H), 7.43 (ddd, J=8.1, 7.1, 1.1 Hz, 1H), 6.85 (s, 1H);
13C NMR (75 MHz, CDCl3): d=178.5, 163.5, 156.3, 133.8,
131.8, 131.6, 129.1, 126.3, 125.7, 125.3, 124.0, 118.1, 107.;
GC-MS (EI, 70 eV): m/z (%)=222 (100), 194 (48), 165 (13),
120 (66), 97 (14), 92 (43), 10 (82); HR-MS (EI): m/z=
222.06730, calcd. for C15H10O2 [M]+: 222.06753.
(E)-1,2-Diphenylvinyl 2-fluorobenzoate (9): light yellow
solid; 1H NMR (300 MHz, CDCl3): d=8.01 (td, J=7.5,
1.9 Hz, 1H), 7.59–7.46 (m, 5H), 7.34–7.11 (m, 8H), 6.72 (s,
1H); 13C NMR (100 MHz, CDCl3): d=162.38 (d, J=
259 Hz), 162.01 (d, J=3.8 Hz), 146.46, 135.54, 135.48 (d, J=
9.8 Hz), 134.19, 132.78, 128.80, 128.70, 128.66 (d, J=12 Hz),
127.71, 124.97, 124.35 (d, J=3.8 Hz), 117.76 (d, J=9.8 Hz),
117.53, 117.24; 19F NMR (282 MHz, CDCl3): d=À107.03
Adv. Synth. Catal. 2016, 358, 466 – 479
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
477

UPDATES
Chaoren Shen et al.
the solution. After evaporation of the organic solvent, the
crude product was purified by column chromatography
using ethyl acetate/n-pentane 1:10 as eluent.
tanecki, L. Paul, J. Tambor, Ber. Dtsch. Chem. Ges.
1901, 34, 2475–2479; c) R. A. Irgashev, V. Y. Sosnov-
skikh, N. Kalinovich, O. Kazakova, G.-V. Rçschenthal-
er, Tetrahedron Lett. 2009, 50, 4903–4905.
2,4-13C2-2,3-Diphenyl-4H-chromen-4-one (3a2): white
solid; 1H NMR (400 MHz, CDCl3): d=8.29 (dd, J=8.0,
1.6 Hz, 1H), 7.70 (dt, J=7.6, 1.6 Hz, 1H), 7.53 (d, J=
8.4 Hz, 1H), 7.45–7.21 (m, 11H); 13C NMR (100 MHz,
CDCl3) d=177.4 (13C-enriched), 161.5 (13C-enriched), 156.1
(t, J=1.2 Hz), 133.3 (dd, J=65, 2.5 Hz), 132.9 (d, J=
3.7 Hz), 131.3, 130.1, 129.6 (d, J=1.9 Hz), 128.3, 128.1 (d,
J=4.3 Hz), 127.6, 126.4, 125.1 (d, J=3.6 Hz), 123.5 (d, J=
54 Hz), 123.0 (dd, J=54, 20 Hz), 118.0 (q, J=2.2 Hz); HR-
MS (ESI): m/z=301.1137, calcd. for C1913C2H15O2 [M+H]+:
301.1139.
[6] a) S. v. Kostanecki, A. Rozycki, Ber. Dtsch. Chem. Ges.
1901, 34, 102–109; b) J. Allan, R. Robinson, J. Chem.
Soc. 1924, 125, 2192–2195; modification of the Kosta-
necki–Robinson reaction: c) J. H. Looker, J. H. McMe-
chan, J. W. Mader, J. Org. Chem. 1978, 43, 2344–2347.
[7] a) U. S. Cheema, K. Venkataraman, J. Chem. Soc. 1932,
918–925; b) W. Baker, J. Chem. Soc. 1933, 1381–1389;
c) T. C. Chadha, H. S. Mahal, K. Venkataraman, J.
Chem. Soc. 1933, 1459–1462; d) H. S. Mahal, K. Venka-
taraman, J. Chem. Soc. 1934, 1767–1769; e) T. SzØll, Gy.
Schçbel, L. Balµspiri, Tetrahedron 1969, 25, 707–714;
f) E. Müller, T. Kµlai, J. Jekç, K. Hideg, Synthesis 2000,
1415; g) S.-S. Wen, J. Wang, Y.-M. Luo, H. Yang, Tetra-
hedron 2014, 70, 9314–9320.
Acknowledgements
[8] C. Zhou, A. V. Dubrovsky, R. C. Larock, J. Org. Chem.
The authors thank the State of Mecklenburg-Vorpommern,
the Bundesministerium für Bildung und Forschung (BMBF),
and the Deutsche Forschungsgemeinschaft for financial sup-
port. Thanks also go to China Scholarship Council (CSC)
for their financial support to C. Shen (No. 201406230040).
We also thank Dr. C. Fischer, S. Schareina, and S. Buchholz
for their excellent technical and analytical support. We also
appreciate the general support from Prof. Matthias Beller.
2006, 71, 1626–1632.
[9] M. Shimizu, H. Tsurugi, T. Satoh, M. Miura, Chem.
Asian J. 2008, 3, 881–886.
[10] a) V. N. Kalinin, M. V. Shostakovsky, A. B. Ponamar-
yov, Tetrahedron Lett. 1990, 31, 4073–4076; b) S. Torii,
H. Okumoto, L.-H. Xu, M. Sadakane, M. V. Shostakov-
sky, A. B. Ponomaryov, V. N. Kalinin, Tetrahedron 1993,
49, 6773–6784; c) Q. Yang, H. Alper, J. Org. Chem.
2010, 75, 948–950.
[11] Original reports on Pd-catalyzed carbonylation: a) A.
Schoenberg, I. Bartoletti, R. F. Heck, J. Org. Chem.
1974, 39, 3318–3326; b) A. Schoenberg, R. F. Heck, J.
Org. Chem. 1974, 39, 3327–3331; c) A. Schoenberg,
R. F. Heck, J. Am. Chem. Soc. 1974, 96, 7761–7764; re-
lated books for carbonylation reactions: d) Modern
Carbonylation Methods, (Ed.: L. Kollµr), Wiley-VCH,
Weinheim, 2008; e) Catalytic Carbonylation Reactions,
(Ed.: M. Beller), Springer, Berlin, 2006; f) Applied Ho-
mogeneous Catalysis with Organometallic Compound-
s,(Eds.: B. Cornils, W. A. Herrmann), Wiley-VCH,
Weinheim, 2002; g) J. Tsuji, Palladium Reagents and
Catalysts, Wiley, Chichester, 1995; h) Transition Metals
for Organic Synthesis: Building Blocks and Fine Chemi-
cals, 2nd edn., (Eds.: M. Beller, C. Bolm), Wiley-VCH,
Weinheim, 2004 selected representative reviews on car-
bonylations: i) A. Brennführer, H. Neumann, M.
Beller, Angew. Chem. 2009, 121, 4176–4196; Angew.
Chem. Int. Ed. 2009, 48, 4114–4133; j) X.-F. Wu, H.
Neumann, M. Beller, Chem. Soc. Rev. 2011, 40, 4986–
5009; k) X.-F. Wu, H. Neumann, ChemCatChem 2012,
4, 447–458; l) X.-F. Wu, H. Neumann, M. Beller, Chem-
SusChem 2013, 6, 229–241.
References
[1] A. Gaspar, M. J. Matos, J. Garrido, E. Uriarte, F.
Borges, Chem. Rev. 2014, 114, 4960–4992.
[2] Selected examples: a) P. Valenti, A. Bisi, A. Rampa, F.
Belluti, S. Gobbi, A. Zampiron, M. Carrara, Bioorg.
Med. Chem. 2000, 8, 239–246; b) A. K. Verma, R.
Pratap, Nat. Prod. Rep. 2010, 27, 1571–1593; c) J.
Rocha-Pereira, R. Cunha, D. C. G. A. Pinto, A. M. S.
Silva, M. S. J. Nascimento, Bioorg. Med. Chem. 2010,
18, 4195–4201.
[3] See, for examples: a) A. Saeed, A. P. Sharma, N.
Durani, R. Jain, S. Durani, R. S. Kapil, J. Med. Chem.
1990, 33, 3210–3216; b) A. P. Sharma, A. Saeed, N.
Durani, R. Jain, S. Durani, R. S. Kapil, J. Med. Chem.
1990, 33, 3216–3222; c) E. S. C. Wu, J. T. Loch III, B. H.
Toder, A. R. Borrelli, D. Gawlak, L. A. Radov, N. P.
Gensmante, J. Med. Chem. 1992, 35, 3519–3525; d) C.
Dyrager, L. N. Mçllers, L. K. Kjäll, J. P. Alao, P. DinØr,
F. K. Wallner, P. Sunnerhagen, M. Grøtli, J. Med.
Chem. 2011, 54, 7427–7431; e) G.-H. Yan, X.-F. Li, B.-
C. Ge, X.-D. Shi, Y.-F. Chen, X.-M. Yang, J.-P. Xu, S.-
W. Liu, P.-L. Zhao, Z.-Z. Zhou, C.-Q. Zhou, W.-H.
Chen, Eur. J. Med. Chem. 2015, 90, 251–257.
[12] X.-F. Wu, H. Neumann, M. Beller, Chem. Rev. 2013,
113, 1–35.
[13] Selected examples: a) X.-F. Wu, H. Neumann, M.
Beller, Chem. Eur. J. 2012, 18, 12595–12598; b) J. Chen,
K. Natte, A. Spannenberg, H. Neumann, M. Beller, X.-
F. Wu, Chem. Eur. J. 2014, 20, 14189–14193; c) K.
Natte, J. Chen, H. Li, H. Neumann, M. Beller, X.-F.
Wu, Chem. Eur. J. 2014, 20, 14184–14188.
[14] Selected recent examples: a) J. Chen, K. Natte, A.
Spannenberg, H. Neumann, P. Langer, M. Beller, X.-F.
Wu, Angew. Chem. 2014, 126, 7709–7713; Angew.
[4] a) R. Schipfer, O. S. Wolfbeis, A. Knierzinger, J. Chem.
Soc. Perkin Trans. 2 1981, 1443–1448; b) M. I. Lvov-
skaya, A. D. Roshal, A. O. Doroshenko, A. V. Kyry-
chenko, V. P. Khilya, Spectrochim. Acta Part A 2006,
65, 397–405.
[5] a) G. P. Ellis, Chromenes, Chromanones, and Chro-
mones: in: The Chemistry of Heterocyclic Compounds,
(Ed.: G. P. Ellis,), John Wiley & Sons, Inc., New York,
1977; Vol. 31, pp 495–555; original report: b) S. v. Kos-
478
asc.wiley-vch.de
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2016, 358, 466 – 479

UPDATES
Palladium-Catalyzed Carbonylative Synthesis of 2,3-Disubstituted Chromones
Chem. Int. Ed. 2014, 53, 7579–7583; b) J. Chen, K.
[21] a) L. Claisen, E. Haase, Ber. Dtsch. Chem. Ges. 1900,
33, 3778–3784; b) L. CIaisen, E. Haase, Ber. Dtsch.
Chem. Ges. 1903, 36, 3674–3682; c) W. Dieckmann, R.
Stein, Ber. Dtsch. Chem. Ges. 1904, 37, 3370–3384;
d) A. Michael, G. H. Carlson, J. Am. Chem. Soc. 1935,
57, 165–174; e) F. Gogan, A. E. OꢂBriain, E. M. Philbin,
N. S. OꢂConnor, R. F. Timoney, T. S. Wheeler, Tetrahe-
dron 1958, 3, 140–143.
Natte, H. Neumann, X.-F. Wu, Chem. Eur. J. 2014, 20,
16107–16110; Corrigendum: J. Chen, K. Natte, H. Neu-
mann, X.-F. Wu, Chem. Eur. J. 2015, 21, doi:
chem.201504244; c) C. Shen, H. Neumann, X. F. Wu,
Green Chem. 2015, 17, 2994–2999; d) C. Shen, X. F.
Wu, Catal. Sci. Technol. 2015, 5, 4433–4443.
[15] A. C. Tadd, M. R. Fielding, M. C. Willis, Chem.
Commun. 2009, 6744–6746.
[16] J. A. Cella, S. W. Bacon, J. Org. Chem. 1984, 49, 1122–
1125.
[22] J. Deutsch, H.-J. Niclas, J. Prakt. Chem. 1993, 335, 69–
74.
´
[23] E. Kolehmainen, B. Osmiałowski, M. Nissinen, R.
[17] CCDC 1403858 (3a) contains the supplementary crys-
tallographicdata for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
[18] a) T. Kobayashi, M. Tanaka, Tetrahedron Lett. 1986, 27,
4745–4748; b) J. Schranck, A. Tlili, H. Neumann, P. G.
Alsabeh, M. Stradiotto, M. Beller, Chem. Eur. J. 2012,
18, 15592–15597.
[19] a) T. M. Gøgsig, R. H. Taaning, A. T. Lindhardt, T.
Skrydstrup, Angew. Chem. 2012, 124, 822–825; Angew.
Chem. Int. Ed. 2012, 51, 798–801; b) J. Schranck, A.
Tlili, P. G. Alsabeh, H. Neumann, M. Stradiotto, M.
Beller, Chem. Eur. J. 2013, 19, 12624–12628; c) D. U.
Nielsen, C. Lescot, T. M. Gøgsig, A. T. Lindhardt, T.
Skrydstrup, Chem. Eur. J. 2013, 19, 17926–17938.
[20] Y. Hu, J. Liu, Z. Lü, X. Luo, H. Zhang, Y. Lan, A. Lei,
J. Am. Chem. Soc. 2010, 132, 3153–3158.
Kauppinena, R. Gawinecki, J. Chem. Soc. Perkin Trans.
2 2000, 2185–2191.
[24] a) F. G. Bordwell, Acc. Chem. Res. 1988, 21, 456–463;
b) F. G. Bordwell, J. A. Harrelson, Can. J. Chem. 1990,
68, 1714–1718; acetophenone pKa =24.7 in DMSO; de-
oxybenzoin pKa =17.7 in DMSO; 1,3-diphenylacetone
pKa =18.7 in DMSO.
[25] a) H. Lütjens, A. Zickgraf, H. Figler, J. Linden, R. A.
Olsson, P. J. Scammells, J. Med. Chem. 2003, 46, 1870–
1877; b) A. J. Walkinshaw, W. Xu, M. G. Suero, M. J.
Gaunt, J. Am. Chem. Soc. 2013, 135, 12532–12535.
[26] R. J. Fitzmaurice, Z. C. Etheridge, E. Jumel, D. N.
Woolfson, S. Caddick, Chem. Commun. 2006, 4814–
4816.
[27] The 13C-labelled deoxybenzoin was synthesized by
adapting the reported method to a two-chamber system
using 13COgen: X.-F. Wu, J. Schranck, H. Neumann, M.
Beller, Chem. Asian J. 2012, 7, 40–44.
Adv. Synth. Catal. 2016, 358, 466 – 479
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
479