Rhodium(I)-Catalyzed CO-Gas-Free Arylative Dual-Carbonylation of Alkynes with Arylboronic Acids via the Formyl C-H Activation of Formaldehyde

Article abstract of DOI:10.1055/a-1468-8377

The rhodium(I)-catalyzed reaction of alkynes with aryl boronic acids in the presence of formaldehyde results in a CO-gas-free arylative dual-carbonylation to produce γ-butenolide derivatives. The simultaneous loading of phosphine-ligated and phosphine-free rhodium(I) complexes is required for efficient catalysis. The former complex catalyzes the abstraction of a carbonyl moiety from formaldehyde through the activation of its formyl C-H bond (decarbonylation) and the latter catalyzes the subsequent dual-incorporation of the resulting carbonyl unit (carbonylation). The use of larger amounts of the phosphine-ligated rhodium(I) complex generates more carbonyl units, leading to the formation γ-butenolides via the dual-incorporation of the carbonyl unit.

Full text of DOI:10.1055/a-1468-8377

SYNTHESIS
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2021, 53, A–K
special topic
A
Bond Activation – in Honor of Prof. Shinji
T. Morimoto et al.
Special Topic
Synthesis
Rhodium(I)-Catalyzed CO-Gas-Free Arylative Dual-Carbonylation
of Alkynes with Arylboronic Acids via the Formyl C–H Activation
of Formaldehyde
Tsumoru Morimoto*a
Chuang Wanga
Hiroki Tanimotob
Levent Artokc
0
0
0
0
-
0
0
0
2
-
1
9
5
6
-
8
7
7
7
R
R
[RhCl(cod)]2/dppp
(Rh/P = 5:10)
R
+
Ar B(OH)2
C
O
(CH2O)n
C
Ar
O
R
(X = H, CH2OH)
X
Formyl C–H
Activation
Kiyomi Kakiuchia
O
O
C
Rh
C
H
a Division of Materials Science, Graduate School of Science and Technology,
Nara Institute of Science and Technology (NAIST), Ikoma, Nara 630-0192,
Japan
H
H
H
Rh
morimoto@ms.naist.jp
b Academic Assembly, Faculty of Pharmaceutical Sciences, University of
Toyama, 2630 Sugitani, Toyama 930-0194, Japan
c Department of Chemistry, Faculty of Science, Izmir Institute of Technology,
Urla 35430, Izmir, Turkey
Published as part of the Special Topic Bond Activation – in Honor of Prof. Shinji Murai
Corresponding Author
Received: 12.03.2021
Accepted after revision: 29.03.2021
Published online: 29.03.2021
bonyl species (aldehyde decarbonylation) (Scheme 1, b).2
This reaction has mainly been used in the multi-step syn-
thesis of complex organic compounds to remove an unnec-
essary carbonyl unit from the final product after carbonyl-
based chemical transformations.3
DOI: 10.1055/a-1468-8377; Art ID: ss-2021-f0130-st
Abstract The rhodium(I)-catalyzed reaction of alkynes with aryl-
boronic acids in the presence of formaldehyde results in a CO-gas-free
arylative dual-carbonylation to produce -butenolide derivatives. The si-
multaneous loading of phosphine-ligated and phosphine-free rhodi-
um(I) complexes is required for efficient catalysis. The former complex
catalyzes the abstraction of a carbonyl moiety from formaldehyde
through the activation of its formyl C–H bond (decarbonylation) and
the latter catalyzes the subsequent dual-incorporation of the resulting
carbonyl unit (carbonylation). The use of larger amounts of the phos-
phine-ligated rhodium(I) complex generates more carbonyl units, lead-
ing to the formation -butenolides via the dual-incorporation of the car-
bonyl unit.
H
O
R
O
R
(a)
C
C
H
O
R
M
C M H
Formyl C–H
Activation
R
+
R H
(b)
OC
M
OC
M
H
Scheme 1 Transition-metal complexes activate formyl C–H bonds of
aldehydes
Key words C–H activation, decarbonylation, rhodium, formaldehyde,
-butenolides, alkynes, arylboronic acids
In the last two decades, new chemical reactions have
been developed in which the carbonyl units generated in
the reaction system by decarbonylation via activation of the
formyl C–H bond of the aldehyde are utilized as a carbonyl
source, leading to carbonylation without the direct need for
carbon monoxide (transfer carbonylation).4 Since our report
of the first example of a transfer carbonylation in which al-
dehydes are used as a carbonyl source,5 we have given pri-
ority to focus on transfer carbonylation reactions in which
the decarbonylation of aldehydes and the insertion of the
resulting carbonyl moiety into a substrate (carbonylation)
are catalyzed by a separate transition-metal complex, re-
spectively, in an attempt to expand the application of the
method.6 Among these types of reactions, we focused on
carbonylation reactions that are catalyzed by a phosphine-
free rhodium(I) complex, proceeding by a transfer carbon-
ylation method using aldehydes, because such complexes
can catalyze various carbonylative transformation reactions
Transition-metal complexes, especially those of late-
transition metals, activate the formyl C–H bond of an alde-
hyde which is then cleaved to form an acyl-metal-hydride
species (RCO-M-H) (Scheme 1). This type of activation rep-
resents a new synthetic transformation that is different
from the conventional mode, which leads to the creation of
a new C–C bond between the highly electron-deficient car-
bonyl carbon of an aldehyde and the electron-rich carbon of
a nucleophile. The addition of an acyl-metal-hydride spe-
cies to an unsaturated bond, such as an alkene or an alkyne,
leads to hydroacylation and the production of ketones
(Scheme 1, a).1 Furthermore, the acyl group of the acyl-
metal-hydride species undergoes migratory extrusion (-
elimination), followed by the reductive elimination of the
organic group (R) and the hydride (H) to give a metal car-
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–K
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
T. Morimoto et al.
Special Topic
Synthesis
and are unique to rhodium catalysis.7 Rhodium complexes
that contain phosphine ligands are generally more effective
for the decarbonylation of aldehydes.2a–e Therefore, it would
appear that the nature of highly active catalysts are in con-
flict with one another when the transfer carbonylation
strategy is applied to phosphine-free rhodium(I)-catalyzed
carbonylation reactions. The key to solving this problem
was the simultaneous use of both phosphine-ligated and
phosphine-free rhodium species in the same reaction.
These two different types of complexes effectively catalyze
decarbonylation and carbonylation processes without in-
terfering with each other, thus resulting in an overall highly
efficient carbonylation transfer.6a,6c–g
Herein we report on the catalytic transfer carbonylative
synthesis of -butenolides from alkynes and arylboronic
acids using formaldehyde as the carbonyl source via activa-
tion of its formyl C–H bond by a rhodium(I) complex
(Scheme 2, a). We previously reported that a lower molar
ratio of the rhodium(I) center and the phosphorous atom
than that used in the present catalysis produces a different
transfer carbonylation product, namely ,-unsaturated
enones from the combination of the same substrate
(alkynes), the reaction partner (an arylboronic acid), and
the carbonyl source (formaldehyde) (Scheme 2, b).6c Thus, a
higher molar ratio of the rhodium(I) center and the phos-
phorous atom leads to an increased formation of a phos-
phine-ligated rhodium(I) complex, resulting in an increase
in the in situ generation of the carbonyl unit via the activa-
tion of the formyl C–H bond of formaldehyde. As a result, it
permits two carbonyl moieties to be incorporated into one
alkyne to give -butenolide derivatives. -Butenolides and
their corresponding saturated analogues are important
frameworks that are commonly found in natural products,
in particular, biologically active compounds.8 The present
method provides an accessible route to such derivatives us-
ing readily available starting materials.
bonyl moiety to give the enone 5a in 32% (entry 1). As the
amount of added dppp was increased from 0 mol% to 10
mol% with 5 mol% of [RhCl(cod)]2, the use of 10 mol% of
dppp led to the formation of the -butenolides 3a and 4a in
64% yield, both of which were formed via the dual-insertion
of the carbonyl moiety (entries 2–5). Based on previous re-
ports that, under phosphine-free rhodium(I) catalyst condi-
tions, a low pressure of carbon monoxide gives the mono-
carbonyl insertion product 5a, and when pressurized car-
bon monoxide is used, the dual-carbonyl insertion product
3a is formed;10 these results indicate that an increase in the
amount of dppp results in an increase in the amount of car-
bonyl moiety that is generated through the formyl C–H ac-
tivation of formaldehyde, leading to an increase in the for-
mation of the -butenolide framework. On the contrary,
when the amount of dppp was further increased (12 mol%
and 20 mol%), the formation of -butenolides decreased
(entries 6 and 7). Under conditions utilizing 5 mol% of [Rh-
Cl(cod)]2 and 10 mol% of dppp, the decarbonylation of
formaldehyde and the dual-insertion of the resulting car-
bonyl moiety are the most cooperative.
Table 1 Effect of dppp on the Rhodium(I)-Catalyzed Reaction of 1a
a
with 2a Using (CH2O)n
[RhCl(cod)]2 (5 mol%)
dppp
Ph
+
PhB(OH)2
+
(CH2O)n
dioxane, 80 °C, 20 h
Ph
1
2a
(5 equiv)
(2 equiv)
Ph
O
Ph
C
+
C
O
Ph
Ph
C
Ph
O
Ph
X
3a (X = H)
5a
4a (X = CH2OH)
Entry
Dppp (mol%)
Yield (%)b
3a + 4a (3a/4a)
5a
32
R
dppp
(Rh/P = 5:10)
R
R
1
2
3
4
5
6
7
0
2
0
(a)
C
O
6 (1:5)
29 (4:25)
49 (7:42)
64 (8:56)
17 (3:14)
0
45
13
21
5
R
C
Ar
O
X
O
C
5
[RhCl(cod)]2
(X = H/CH2OH)
8
H
H
O
C
Ar B(OH)2
10
12
20
(b)
Ar
R
BIPHEP
3
(Rh/P = 5:1)
R
0
Scheme 2 Phosphine-ligated and phosphine-free Rh(I)-catalyzed car-
bonylation reactions using formaldehyde as the carbonyl source
a Reaction conditions: 1 (1 mmol), 2a (2 mmol), paraformaldehyde
(5 mmol), dppp, [RhCl(cod)]2 (5 mol%), dioxane (1 mL), 80 °C, 20 h.
b Isolated yield.
We first examined the reaction of diphenylacetylene (1)
with phenylboronic acid (2a) and paraformaldehyde under
the rhodium(I) catalytic conditions, which consist of
[RhCl(cod)]2 (cod = 1,5-cyclooctadiene) and dppp9 (Table 1).
The reaction of 1 with 2a and paraformaldehyde in the
presence of a catalytic amount of only [RhCl(cod)]2 resulted
in the hydrobenzoylation via the mono-insertion of a car-
Under catalytic conditions consisting of 5 mol% of [Rh-
Cl(cod)]2 and 10 mol% of diphosphine, the effect of other di-
phosphines on the product distribution was investigated.
The use of dppp was found to be effective in the following
catalytic systems: BIPHEP, 16% (3a/4a = 3%/13%) and 4%
(5a); BINAP, 9% (3a/4a = 1%/8%) and 5% (5a); dppf, 8% (3a/4a
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–K

C
T. Morimoto et al.
Special Topic
Synthesis
= 1%/7%) and 3% (5a); dppb, 7% (3a/4a = 1%/6%) and 5%
(5a).9 When
rhodium(I)-alkene complex, such as
tial formation of some dppp-ligated Rh(I) complexes, along
with intact [RhCl(cod)]2. The former dppp-ligated Rh(I) spe-
cies functions to mainly decarbonylate formaldehyde via
activation of the formyl C–H bond of formaldehyde to gen-
erate the carbonyl unit and hydrogen (Cycle I), while the
latter predominantly catalyzes the actual arylative carbon-
ylation process. Thus, Rh(I)–OH (A) generated in situ from
Rh(I)–Cl and H2O is transmetalated with PhB(OH)2 to gener-
ate Rh(I)–Ph (B). The carbonyl unit from the decarbonyla-
tion process that is catalyzed by the phosphine-ligated Rh(I)
complex is transferred to B [the formation of Ph–Rh–CO
(C)], which is followed by the migratory insertion of CO into
the Ph–Rh bond in C to yield the PhCO–Rh intermediate (D).
The subsequent benzoylrhodation to alkyne 1 in a syn-
manner, followed by protonation of the formed vinylrhodi-
um E, produces the primary enone product (E)-5a, along
with the regeneration of A. (E)-5a isomerizes to give an
equilibrium mixture of (E)- and (Z)-5a under the rhodi-
um(I)-catalytic conditions in the presence of an acidic aryl-
boronic acid.6c Furthermore, when a larger amount of dppp
is added, this results in the generation of more carbonyl
units. The second carbonyl unit from Cycle I is then inserted
into the Rh(I)–carbon bond in E to form the complex F, fol-
lowed by ring-closure to yield the -furanonyl-Rh(I) com-
plex G. This step corresponds to the step leading to the for-
mation of the -butenolide framework. Finally, the dis-
placement of Rh(I) from the cyclic complex by reacting with
a proton or formaldehyde leads to the formation of the -
butenolide derivatives 3a and 4a via protonation and a vi-
nylogous aldol reaction16 (Cycle II).
a
[RhCl(cod)]2, was mixed with a phosphine such that the ra-
tio of the rhodium(I) center to the phosphine atom is 1:1,
the addition of biaryl diphosphines such as BIPHEP or
BINAP led to the in situ generation of [RhCl(P—P)]2,11 with
no remaining phosphine-free rhodium(I) species; while in
the case of the other diphosphines that were examined
(dppf, dppb, and dppp), four phosphorus atoms at most can
coordinate to one rhodium(I) center, leading to the partial
formation of RhCl(P—P)2.12 As a result, the loaded rhodi-
um(I) is divided into the diphosphine-ligated species and
the intact form. In fact, in a mixture of [RhCl(C2H4)2]213 and
dppp in a molar ratio of 1:2 in CDCl3, two types of phos-
phine-ligated rhodium species were formed, which can be
assigned to RhCl(dppp)2 at 8.3 ppm and [RhCl(dppp)]2 at
33.9 ppm in a molar ratio of 8.00:4.83 (Figure 1).14 It is
known that such complexes, RhCl(dppp)2 and [RhCl(dppp)]2,
show catalytic activity for the decarbonylation of alde-
hydes.15 In addition, the fact that there is no remaining
dppp at –17.2 ppm (based on 31P NMR observations) and
that RhCl(dppp)2 is predominantly formed indicates that
intact [RhCl(C2H4)2]2 is present in the reaction mixture, i.e.,
dppp-ligated rhodium(I) complexes and a dppp-free rhodi-
um(I) species are simultaneously involved in the catalysis.
It therefore follows that these complexes would be involved
in the decarbonylation of formaldehyde and the arylative
dual-carbonylation processes, respectively.
A plausible reaction pathway for the present reactions is
shown in Scheme 3. As in our previous report,6a,6c–g the ad-
dition of dppp, the amount of which cannot be equivalent
to that of all of the loaded rhodium metal, leads to the par-
H
H
OC
H
P
C
H
P
Rh
P
O
Rh
P
Cl
Formyl C–H
Activation
Cl
O
– H2
[Cycle I]
C
H
H
Cl
Cl
P
CO
Rh
Rh
P
P
P
Rh Cl
H2O – HCl
Ph
O
CO
2a
CO
C
Ph Rh
Rh OH
– B(OH)3
First
Transfer
Ph Rh
Rh
A
B
C
D
3a (X = H)
H2O
4a (CH2OH)
B(OH)n
HCHO
[Cycle II]
1
O
Rh
O
O
C
Rh
Second
Transfer
O
C
C
O
C
Ph
C
Ph
Ph
CO
Ph
Ph
Rh
Ph
Ph
Ph
F
Ph
Cycle I
G
E
H2O
B(OH)n
Rh = Phosphine-free Rh(I)
(E)- and (Z)-5a
Figure 1 31P NMR spectrum of a mixture of [RhCl(cod)]2 and dppp in a
Scheme 3 A plausible reaction pathway
molar ratio of 1:2
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–K

D
T. Morimoto et al.
Special Topic
Synthesis
With the above-mentioned standard conditions in
hand, the scope of arylboronic acids in the reaction with 1
was next investigated (Table 2). Electronic properties of re-
actants have a strong effect on the dual-incorporation pro-
cess. Thus, reactions of arylboronic acids possessing an
electron-donating group at the para-position of the aro-
matic ring, such as p-methoxyphenylboronic acid (2b) and
p-methylphenylboronic acid (2c), afforded the correspond-
ing dual-carbonylative products 3b/4b and 3c/4c in 77% and
71% total yields (entries 1 and 2). On the contrary, the intro-
duction of an electron-withdrawing group to the arylbo-
ronic acid (p-Cl: 2d, p-CF3: 2e) resulted in a decrease in the
yields of the dual-carbonylated products 3d/4d (58%) and
3e/4e (48%), while the yields of the mono-carbonylated
products 5d and 5e were slightly increased (entries 4 and
5). As the substituent (OMe) on the aromatic ring of the
arylboronic acid was shifted from the p- (2b) to the m- (2f)
and o-positions (2g), the yield of the arylative dual-carbon-
ylated products (3b/4b, 3f/4f, and 3g/4g) decreased, and
small amounts of the arylative mono-carbonylated prod-
ucts 5b, 5f, and 5g were formed (entries 1, 6 and 7).
(entries 1 and 4). The reactions of 6 or 9 with various para-
substituted arylboronic acids 2 showed the same tendency
for the production of -butenolides 7, 8, 10 and 11 as that
observed for entries 1, 3 and 5 in Table 2. Thus, a more elec-
tron-donating substituent (OMe) led to the formation of
higher yields of the -butenolides 7, 8, 10 and 11 (entries
1–6).
a
Table 3 Reactions of Various Alkynes with 2 Using (CH2O)n
R
[RhCl(cod)]2 (5 mol%)
dppp (10 mol%)
R
R
+
ArB(OH)2
C O
dioxane, 80 °C, 20 h
(CH2O)n (5 equiv)
C
Ar
R
O
6, 9
2 (2 equiv)
X
7, 10 (X = H)
8, 11 (X = CH2OH)
Entry Alkyne (R)
Arylboronic acid (2) Yield (%)b
-Butenolides (X = H/CH2OH)
1
2
3
4
5
6
4-MeOC6H4 (6) 4-MeOC6H4 (2b)
68 [7b (13)/8b (55)]
60 [7a (11)/8a (49)]
46 [7e (11)/8e (35)]
63 [10b (6)/11b (57)]
47 [10a (5)/11a (42)]
26 [10e (0)/11e (26)]
6
C6H5 (2a)
6
4-CF3C6H4 (2e)
Table 2 Reaction of 1a with Various Arylboronic Acids 2 Using
4-F3CC6H4 (9)
2b
2a
2e
a
(CH2O)n
9
9
[RhCl(cod)]2 (5 mol%)
dppp (10 mol%)
Ph
a Reaction conditions: alkyne (1 mmol), 2 (2 mmol), paraformaldehyde
(5 mmol), [RhCl(cod)]2 (5 mol%), dppp (10 mol%), dioxane (1 mL), 80 °C,
+
ArB(OH)2
+
(CH2O)n
dioxane, 80 °C, 20 h
Ph
1
2a–g
(5 equiv)
20 h.
(2 equiv)
b Isolated yield.
Ph
O
Ph
C
+
C
O
In conclusion, we have reported herein on the rhodi-
um(I)-catalyzed reaction of alkynes with arylboronic acids
in the presence of formaldehyde, resulting in a CO-gas-free
arylative dual-carbonylation to yield -butenolide deriva-
tives. The simultaneous loading of phosphine-ligated and
phosphine-free rhodium(I) complexes is required for effi-
cient catalysis and thus higher yields. The former complex
catalyzes the abstraction of a carbonyl moiety from formal-
dehyde through the activation of its formyl C–H bond (de-
carbonylation) and the latter catalyzes the subsequent in-
corporation of the resulting carbonyl unit (arylative dual-
carbonylation). The use of larger amounts of the phos-
phine-ligated rhodium(I) complex generates more carbonyl
units, thus leading to the formation -butenolides via the
incorporation of two carbonyl units. The present method
provides an accessible route to these types of derivatives
using readily available starting materials.
Ar
Ph
C
Ar
O
Ph
X
3a–g (X = H)
5a–g
4a–g (X = CH2OH)
Entry
Arylboronic acid 2
Yield (%)b
3 + 4 (3/4)
5
1
2
3
4
5
6
7
4-MeOC6H4 (2b)
4-MeC6H4 (2c)
C6H5 (2a)
77 [3b (10)/4b (67)]
71 [3c (11)/4c (60)]
64 [3a (8)/4a (56)]
58 [3d (9)/4d (49)]
48 [3e (7)/4e (41)]
63 [3f (10)/4f (53)]
16 [3g (12)/4g (4)]
5b (4)
5c (5)
5a (5)
5d (8)
5e (9)
5f (5)
5g (1)
4-ClC6H4 (2d)
4-F3CC6H4 (2e)
3-MeOC6H4 (2f)
2-MeOC6H4 (2g)
a Reaction conditions: 1 (1 mmol), 2 (2 mmol), paraformaldehyde (5 mmol),
[RhCl(cod)]2 (5 mol%), dppp (10 mol%), dioxane (1 mL), 80 °C, 20 h.
b Isolated yield.
The results obtained from the reactions of other inter-
nal alkynes under the present arylative dual-carbonylation
reaction conditions are summarized in Table 3. The
reactions of diphenylacetylene derivatives 6 and 9 with
p-MeOC6H4B(OH)2 (2b) gave the corresponding butenolides
7b/8b and 10b/11b in 68% and 63% total yields, respectively
All reactions were carried out in dried glassware under a nitrogen at-
mosphere using anhydrous solvents, unless stated otherwise.
[RhCl(cod)]2 was prepared using a previously reported method.17 1,3-
Bis(diphenylphosphino)propane (dppp), 1,3-bis(diphenylphosphi-
no)butane (dppb), 1,1′-ferrocenediyl-bis(diphenylphosphine) (dppf),
2,2′-bis(diphenylphosphino)biphenyl (BIPHEP), and 2,2′-bis(diphen-
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–K

E
T. Morimoto et al.
Special Topic
Synthesis
ylphosphino)-1,1′-binaphthyl (BINAP) were purchased from Strem
Chemicals, Inc., and used directly without further purification. 1,2-
Diphenylethyne (1) and phosphine ligands were purchased from To-
kyo Chemical Industry Co., Ltd. and used directly without further pu-
rification. Arylboronic acids 2 were purchased from Wako Pure
Chemical Industries, Ltd., and were used directly without further pu-
rification. Paraformaldehyde was purchased from Wako Pure Chemi-
cal Industries, Ltd. and dried over P2O5 under vacuum prior to use. An-
hydrous 1,4-dioxane was purchased from Wako Pure Chemical Indus-
tries, Ltd., and was further dried over 4 Å molecular sieves and
degassed by freeze–pump–thaw cycles (3 times), and then stored in a
glove box. 1,2-Bis(4-methoxyphenyl)ethyne (6) and 1,2-bis[4-(triflu-
oromethyl)phenyl]ethyne (9) were synthesized from commercially
available starting materials according to the reported methods.2c
1650.9(2) Å3, Z = 4, c = 1.257 g/cm3,  = 0.794 cm–1, T = 123 K,  =
0.71075 Å, 15833 reflections, 3373 unique [R(int) = 0.0429], final GoF
= 1.077, R1 = 0.0471 ([I > 2.00(I)]), wR2 = 0.1080 (all data).
5-(Hydroxymethyl)-3,4,5-triphenylfuran-2(5H)-one (4a) (Table 1,
Entry 5)
Yield: 191.7 mg (56%); white solid; mp 143.1–144.6 °C; Rf = 0.28 (hex-
ane/EtOAc, 2:1).
IR (KBr): 3449, 3058, 2925, 1752 (C=O), 1409, 1445, 1178, 1005, 749,
696 cm–1
.
1H NMR (500 MHz, CDCl3):  = 2.36 (s, 1 H), 4.27 (s, 2 H), 6.92 (d, J =
7.0 Hz, 2 H), 7.19–7.39 (m, 13 H).
13C NMR (125 MHz, CDCl3):  = 64.0, 90.9, 125.7, 128.1, 128.3, 128.5,
Reactions were monitored by TLC (Merck TLC Silicagel 60 F254). Ceri-
um phosphomolybdate solution and iodine were used to enable visu-
alization of samples. Merck Silica gel 60 was used for flash column
chromatography. Melting points were obtained using a Yanaco MP-
500D apparatus. Infrared (IR) absorption spectra were measured us-
ing a JASCO FT/IR-4200 spectrophotometer. 1H NMR and 13C NMR
spectra were recorded using a JEOL JNM-ECX500 spectrometer (1H
NMR: 500 MHz, 13C NMR: 126 MHz). The chemical shift values were
adjusted based on the chloroform solvent peak (1H NMR: 7.26 ppm,
13C NMR: 77.0 ppm) as the internal standard. Multiplicities are abbre-
viated as follows: s (singlet), d (doublet), t (triplet), q (quartet), m
(complex multiplet). Mass spectrometry (MS) was performed using a
JEOL JMS-700 Mstation [EI (70 eV)]. HRMS was accomplished with a
JEOL LMS-700 MStation. X-ray crystallography was performed using a
Rigaku R-AXIS RAPID/S imaging plate diffractometer.
128.6, 129.2, 131.7, 135.0, 162.6, 172.5.
MS (EI): m/z (%) = 342 (5) [M+], 312 (63), 311 (60), 284 (3), 265 (7),
252 (6), 207 (40), 179 (50), 178 (49), 152 (6), 105 (100), 77 (35), 51
(4).
HRMS (ESI): m/z [M+] calcd for C23H18O3: 342.1256; found: 342.1254.
Crystallographic data for 4a (CCDC 1002983): C23H18O3, Mr = 342.39,
colorless block, 0.170 × 0.110 × 0.030 mm, orthorhombic, primitive, a
= 24.4574(5) Å, b = 15.1514(3) Å, c = 10.3240(2) Å, V = 3825.7(2) Å3, Z
= 8, c = 1.189 g/cm3,  = 0.779 cm–1, T = 123 K,  = 0.71075 Å, 52627
reflections, 6977 unique [R(int) = 0.0823], final GoF = 1.077, R1
0.0542 ([I > 2.00(I)]), wR2 = 0.1427 (all data).
=
(E)-1,2,3-Triphenyl-2-propen-1-one [(E)-5a] (Table 1, Entry 5)6c
Yield: 5.3 mg (1.9%); white solid; mp 100.1–101.2 °C; Rf = 0.14 (hex-
ane/EtOAc, 30:1).
IR (KBr): 3047, 3021, 1644 (C=O), 1595, 1576, 1444, 1250 cm–1
Catalytic Reactions; General Procedure
.
In a 10 mL screw-capped vial were placed [RhCl(cod)]2 (24.6 mg, 0.05
mmol), dppp (41.4 mg, 0.1 mmol), alkyne 1 (1 mmol), arylboronic
acid 2 (2 mmol), paraformaldehyde (150.2 mg, 5 mmol), and 1,4-di-
oxane (1 mL). The mixture was degassed by three freeze-pump-thaw
cycles and then the vial was sealed under N2. The mixture was stirred
at 80 °C for 20 h, cooled to room temperature and then transferred to
a 50 mL flask using ethyl acetate (10 mL) and treated with 8 g of acti-
vated aluminum oxide (Al2O3) with stirring for 1 h. The reaction mix-
ture was filtered through a short pad of Celite and the filtrate was
concentrated in vacuo. The residue was purified by flash chromatog-
raphy on silica gel.
1H NMR (500 MHz, CDCl3):  = 7.09 (d, J = 7.5 Hz, 2 H), 7.16–7.23 (m, 4
H), 7.27–7.29 (m, 2 H), 7.33–7.36 (m, 3 H), 7.45 (t, J = 8.0 Hz, 2 H), 7.54
(t, J = 7.0 Hz, 1 H), 7.86 (d, J = 7.0 Hz, 2 H).
13C NMR (125 MHz, CDCl3):  = 127.9, 128.2, 128.3, 128.8, 128.9,
129.6, 129.8, 130.3, 132.1, 134.7, 136.5, 138.1, 140.2, 140.7, 197.6.
MS (EI): m/z (%) = 284 (87) [M+], 283 (33), 207 (13), 206 (20), 180 (10),
179 (60), 178 (82), 167 (32), 152 (15), 105 (100), 77 (60), 51 (14).
HRMS (ESI): m/z [M+] calcd for C21H16O: 284.1201; found: 284.1200.
(Z)-1,2,3-Triphenyl-2-propen-1-one [(Z)-5a] (Table 1, Entry 5)6c
Yield: 9.5 mg (3.1%); white solid; mp 85.0–86.7 °C; Rf = 0.20 (hex-
ane/EtOAc, 30:1).
3,4,5-Triphenylfuran-2(5H)-one (3a) (Table 1, Entry 5)10
Yield: 25.0 mg (8.0%); white solid; mp 124.0–125.2 °C; Rf = 0.47 (hex-
ane/EtOAc, 2:1).
IR (KBr): 2923, 2853, 1752 (C=O), 1012, 963, 745, 695 cm–1
1H NMR (500 MHz, CDCl3):  = 6.27 (s, 1 H), 7.11 (d, J = 8.5 Hz, 2 H),
7.21 (t, J = 7.5 Hz, 2 H), 7.31–7.37 (m, 9 H), 7.47–7.48 (m, 2 H).
13C NMR (125 MHz, CDCl3):  = 83.7, 126.8, 127.4, 127.6, 128.1, 128.3,
128.5, 128.7, 128.9, 129.1, 129.2, 129.4, 129.7, 129.9, 131.0, 134.7,
159.3, 172.5.
MS (EI): m/z (%) = 312 (21) [M+], 284 (3), 265 (7), 252 (6), 239 (5), 207
(12), 178 (100), 152 (20), 105 (42), 77 (51), 51 (26).
IR (KBr): 3057, 3025, 2924, 2359, 1666 (C=O), 1596, 1579, 1448, 1224
cm–1
.
.
1H NMR (500 MHz, CDCl3):  = 7.14–7.21 (m, 4 H), 7.29–7.32 (m, 3 H),
7.34–7.38 (m, 4 H), 7.46–7.50 (m, 3 H), 7.99 (d, J = 7.5 Hz, 2 H).
13C NMR (125 MHz, CDCl3):  = 126.3, 128.0, 128.1, 128.4, 128.71,
128.75, 128.8, 129.6, 130.0, 133.6, 135.3, 136.2, 137.9, 140.7, 199.3.
MS (EI): m/z (%) = 284 (100) [M+], 283 (21), 206 (12), 179 (35), 178
(53), 167 (18), 105 (82), 77 (42), 60 (11), 57 (15), 55 (11).
HRMS (ESI): m/z [M+] calcd for C21H16O: 284.1201; found: 284.1201.
HRMS (ESI): m/z [M+] calcd for C22H16O2: 312.1150; found: 312.1152.
3,4-Diphenyl-5-(4-methoxyphenyl)furan-2(5H)-one (3b) (Table 2,
Crystallographic data for 3a (CCDC 1002969): C22H16O2, Mr = 312.37,
colorless block, 0.120 × 0.070 × 0.030 mm, monoclinic, primitive, a =
10.6542(9) Å, b = 8.8328(7) Å, c = 17.640(2) Å,  = 96.005(3)°, V =
Entry 1)10
Yield: 34.2 mg (10%); white solid; mp 112.0–113.1 °C; Rf = 0.39 (hex-
ane/EtOAc, 2:1).
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–K

F
T. Morimoto et al.
Special Topic
Synthesis
IR (KBr): 2921, 2851, 1750 (C=O), 1608, 1514, 1457, 1158 cm–1
.
MS (EI): m/z (%) = 316 (27) [M + 2+], 315 (68) [M + 1+], 314 (100) [M+],
286 (38), 236 (21), 198 (21), 197 (62), 179 (55), 178 (68), 177 (47),
176 (52), 152 (41), 136 (56), 135 (100), 107 (52), 92 (57), 85 (31), 83
(47), 77 (60), 64 (26), 51 (23).
1H NMR (500 MHz, CDCl3):  = 3.78 (s, 3 H), 6.23 (s, 1 H), 6.85 (d, J =
9.0 Hz, 2 H), 7.11 (d, J = 7.0 Hz, 2 H), 7.21–7.27 (m, 5 H), 7.34–7.37 (m,
3 H), 7.46–7.48 (m, 2 H).
13C NMR (125 MHz, CDCl3):  = 55.1, 83.3, 114.2, 126.5, 126.7, 128.3,
128.5, 128.6, 128.7, 129.0, 129.3, 129.7, 129.8, 131.1, 159.2, 160.2,
172.5.
MS (EI): m/z (%) = 342 (55) [M+], 314 (3), 285 (7), 252 (11), 237 (11),
207 (15), 178 (80), 135 (100), 126 (6), 77 (13), 57 (8).
HRMS (ESI): m/z [M+] calcd for C23H18O3: 342.1256; found: 342.1255.
HRMS (ESI): m/z [M+] calcd for C22H18O2: 314.1307; found: 314.1308.
3,4-Diphenyl-5-(4-methylphenyl)furan-2(5H)-one (3c) (Table 2,
Entry 2)10
Yield: 35.9 mg (11%); white solid; mp 119.0–120.2 °C; Rf = 0.47 (hex-
ane/EtOAc, 2:1).
IR (KBr): 3055, 2923, 2853, 1752 (C=O), 1598, 1445, 963, 695 cm–1
.
1H NMR (500 MHz, CDCl3):  = 2.31 (s, 3 H), 6.23 (s, 1 H), 7.10–7.48
3,4-Diphenyl-5-(hydroxymethyl)-5-(4-methoxyphenyl)furan-
(m, 14 H).
2(5H)-one (4b) (Table 2, Entry 1)
Yield: 249.5 mg (67%); white solid; mp 164.6–165.8 °C; Rf = 0.20 (hex-
13C NMR (125 MHz, CDCl3):  = 21.2, 83.6, 127.6, 128.3, 128.5, 128.6,
ane/EtOAc, 2:1).
128.8, 129.4, 129.6, 129.8, 131.1, 131.6, 139.3, 159.3, 172.6.
IR (KBr): 3449, 3057, 3020, 2933, 2837, 1752 (C=O), 1609, 1513, 1255,
MS (EI): m/z (%) = 326 (35) [M+], 298 (3), 269 (5), 252 (7), 221 (11),
207 (32), 178 (100), 176 (30), 152 (20), 119 (65), 91 (35), 57 (10).
833, 760, 698 cm–1
.
1H NMR (500 MHz, CDCl3):  = 2.47–2.49 (m, 1 H), 3.81 (s, 3 H), 4.20–
4.24 (m, 2 H), 6.86 (d, J = 6.0 Hz, 2 H), 6.92 (d, J = 6.5 Hz, 2 H), 7.13 (d,
J = 6.5 Hz, 2 H), 7.23–7.40 (m, 8 H).
HRMS (ESI): m/z [M+] calcd for C23H18O2: 326.1307; found: 326.1306.
3,4-Diphenyl-5-hydroxymethyl-5-(4-methylphenyl)furan-2(5H)-
13C NMR (125 MHz, CDCl3):  = 55.1, 63.8, 90.8, 113.9, 126.8, 127.1,
127.6, 128.0, 128.3, 128.5, 129.0, 129.1, 129.4, 131.7, 159.6, 162.7,
172.6.
one (4c) (Table 2, Entry 2)
Yield: 213.8 mg (60%); white solid; mp 158.8–160.0 °C; Rf = 0.28 (hex-
ane/EtOAc, 2:1).
MS (EI): m/z (%) = 372 (8) [M+], 312 (3), 311 (2), 281 (1), 237 (2), 207
(4), 178 (5), 135 (12), 83 (100), 69 (6), 59 (7).
IR (KBr): 3435, 3057, 3024, 2923, 2876, 1752 (C=O), 1513, 1444, 1180,
1007, 819, 758 cm–1
.
HRMS (ESI): m/z [M+] calcd for C24H20O4: 372.1362; found: 372.1363.
1H NMR (500 MHz, CDCl3):  = 2.35 (s, 3 H), 2.54–2.56 (m, 1 H), 4.20–
4.25 (m, 2 H), 6.93 (d, J = 7.0 Hz, 2 H), 7.11 (dd, J = 30.5, 8.5 Hz, 4 H),
7.22–7.39 (m, 8 H).
(E)-2,3-Diphenyl-1-(4-methoxyphenyl)-2-propen-1-one [(E)-5b]
(Table 2, Entry 1)6c
13C NMR (125 MHz, CDCl3):  = 20.8, 63.7, 90.7, 125.4, 127.4, 127.8,
Yield: 3.3 mg (1.0%); colorless oil; Rf = 0.18 (hexane/EtOAc, 20:1).
128.1, 128.3, 128.9, 129.0, 129.2, 131.5, 131.7, 138.3, 162.4, 172.3.
IR (neat): 3056, 2931, 2838, 1646 (C=O), 1599, 1574, 1312, 1508,
MS (EI): m/z (%) = 356 (8) [M+], 325 (95), 323 (8), 298 (11), 265 (12),
252 (11), 221 (21), 207 (55), 179 (70), 178 (69), 152 (13), 119 (100),
91 (60), 65 (14), 57 (12).
1253, 1166, 1027 cm–1
.
1H NMR (500 MHz, CDCl3):  = 3.87 (s, 3 H), 6.92 (d, J = 8.5 Hz, 2 H),
7.11 (d, J = 7.5 Hz, 2 H), 7.14 (s, 1 H), 7.15–7.24 (m, 3 H), 7.27–7.37 (m,
5 H), 7.90 (d, J = 8.5 Hz, 2 H).
HRMS (ESI): m/z [M+] calcd for C24H20O3: 356.1412; found: 356.1412.
13C NMR (125 MHz, CDCl3):  = 55.5, 113.6, 127.9, 128.2, 128.6, 128.8,
129.5, 130.2, 130.4, 132.3, 135.0, 136.8, 137.8, 141.0, 163.1, 196.3.
(E)-2,3-Diphenyl-1-(4-methylphenyl)-2-propen-1-one [(E)-5c]
(Table 2, Entry 2)6c
MS (EI): m/z (%) = 316 (21) [M + 2+], 315 (70) [M + 1+], 314 (96) [M+],
286 (25), 236 (22), 221 (17), 198 (18), 197 (63), 179 (57), 178 (76),
177 (37), 176 (48), 152 (33), 151 (22), 149 (34), 136 (56), 135 (100),
107 (50), 92 (53), 86 (60), 84 (71), 77 (65), 57 (52).
Yield: 4.0 mg (1.3%); white solid; mp 88.1–89.3 °C; Rf = 0.14 (hex-
ane/EtOAc, 30:1).
IR (KBr): 3044, 1644 (C=O), 1605, 1494, 1448, 1381, 1318, 1264, 1181,
1064 cm–1
.
HRMS (ESI): m/z [M+] calcd for C22H18O2: 314.1307; found: 314.1305.
1H NMR (500 MHz, CDCl3):  = 2.41 (s, 3 H), 7.09 (d, J = 6.5 Hz, 2 H),
7.15–7.37 (m, 11 H), 7.79 (d, J = 8.5 Hz, 2 H).
13C NMR (125 MHz, CDCl3):  = 21.6, 127.8, 128.2, 128.75, 128.73,
129.0, 129.6, 130.0, 130.2, 134.9, 135.3, 136.6, 139.1, 140.9, 143.0,
197.3.
(Z)-2,3-Diphenyl-1-(4-methoxyphenyl)-2-propen-1-one [(Z)-5b]
(Table 2, Entry 1)6c
Yield: 9.4 mg (3.0%); white solid; mp 88.5–89.9 °C; Rf = 0.18 (hex-
ane/EtOAc, 20:1).
MS (EI): m/z (%) = 299 (53) [M + 1+], 298 (71) [M+], 297 (25), 236 (35),
221 (43), 220 (40), 182 (27), 181 (61), 180 (26), 179 (63), 178 (87),
177 (52), 176 (51), 152 (62), 151 (53), 119 (100).
IR (KBr): 3056, 3026, 2932, 2839, 1658 (C=O), 1652, 1595, 1575, 1508,
1258, 1235, 1164 cm–1
.
1H NMR (500 MHz, CDCl3):  = 3.80 (s, 3 H), 6.83 (d, J = 8.5 Hz, 2 H),
7.13–7.22 (m, 4 H), 7.27–7.36 (m, 5 H), 7.47 (d, J = 8.0 Hz, 2 H), 7.97
(d, J = 8.5 Hz, 2 H).
HRMS (ESI): m/z [M+] calcd for C22H18O: 298.1358; found: 298.1357.
(Z)-2,3-Diphenyl-1-(4-Methylphenyl)-2-propen-1-one [(Z)-5c]
(Table 2, Entry 2)6c
13C NMR (125 MHz, CDCl3):  = 55.3, 114.0, 126.2, 127.9, 128.1, 128.4,
128.8, 129.4, 129.5, 132.0, 135.4, 138.1, 140.9, 163.9, 197.8.
Yield: 11.0 mg (3.7%); colorless oil; Rf = 0.18 (hexane/EtOAc, 30:1).
IR (neat): 3056, 3025, 1663 (C=O), 1605, 1492, 1448, 1227, 1174 cm–1
.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–K

G
T. Morimoto et al.
Special Topic
Synthesis
1H NMR (500 MHz, CDCl3):  = 2.33 (s, 3 H), 7.12–7.21 (m, 6 H), 7.26–
7.36 (m, 5 H), 7.46 (d, J = 7.5 Hz, 2 H), 7.89 (d, J = 8.5 Hz, 2 H).
(Z)-1-(4-Chlorophenyl)-2,3-diphenyl-2-propen-1-one [(Z)-5d]
(Table 2, Entry 4)6c
13C NMR (125 MHz, CDCl3):  = 21.7, 126.3, 127.9, 128.1, 128.4, 128.8,
Yield: 174 mg (5.4%); white solid; mp 104.3–105.6 °C; Rf = 0.31 (hex-
ane/EtOAc, 20:1).
129.5, 129.7, 129.9, 133.9, 135.4, 138.1, 140.9, 144.6, 199.0.
MS (EI): m/z (%) = 299 (12) [M + 1+], 298 (52) [M+], 179 (12), 178 (28),
119 (100), 91 (39), 65 (13).
IR (neat): 3082, 3057, 3023, 1663 (C=O), 1596, 1584, 1494, 1450,
1401, 1223, 1176, 1090, 1011 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.14–7.21 (m, 4 H), 7.24–7.37 (m, 7 H),
7.44 (d, J = 8.0 Hz, 2 H), 7.91 (d, J = 7.5 Hz, 2 H).
HRMS (ESI): m/z [M+] calcd for C22H18O: 298.1358; found: 298.1357.
5-(4-Chlorophenyl)-3,4-diphenylfuran-2(5H)-one (3d) (Table 2,
13C NMR (125 MHz, CDCl3):  = 126.3, 128.2, 128.3, 128.5, 128.8,
128.9, 129.1, 130.4, 131.0, 134.7, 135.2, 137.7, 140.1, 140.3, 198.1.
Entry 4)10
MS (EI): m/z (%) = 321 (10) [M + 3+], 320 (44) [M + 2+], 319 (42) [M +
1+], 318 (100) [M+], 317 (32), 283 (47), 206 (12), 179 (38), 178 (48),
139 (50), 111 (16).
Yield: 31.2 mg (9%); white solid; mp 132.0–133.2 °C; Rf = 0.47 (hex-
ane/EtOAc, 2:1).
IR (KBr): 2923, 2853, 1752 (C=O), 1598, 1445, 1156, 963, 852 cm–1
.
HRMS (ESI): m/z [M+] calcd for C21H15ClO: 318.0811; found: 318.0810.
1H NMR (500 MHz, CDCl3):  = 6.25 (s, 1 H), 7.09–7.48 (m, 14 H).
13C NMR (125 MHz, CDCl3):  = 82.8, 128.2, 128.6, 128.8, 128.9, 129.2,
129.3, 129.5, 130.1, 130.8, 133.2, 135.2, 159.0, 172.3.
MS (EI): m/z (%) = 346 (35) [M+], 318 (3), 265 (11), 241 (7), 208 (4),
207 (32), 178 (100), 176 (32), 139 (42), 111 (22), 77 (15), 75 (14), 51
(12).
3,4-Diphenyl-5-[4-(trifluoromethyl)phenyl]furan-2(5H)-one (3e)
(Table 2, Entry 5)10
Yield: 26.6 mg (7%); white solid; mp 132.6–133.7 °C; Rf = 0.47 (hex-
ane/EtOAc, 2:1).
IR (neat): 3059, 2924, 2853, 1758 (C=O), 1446, 1325, 1068, 850 cm–1
1H NMR (500 MHz, CDCl3):  = 6.33 (s, 1 H), 7.12 (d, J = 7.5 Hz, 2 H),
7.23–7.48 (m, 10 H), 7.58 (d, J = 7.0 Hz, 2 H).
.
HRMS (ESI): m/z [M+] calcd for C22H15ClO2: 346.0761; found:
346.0761.
5-(4-Chlorophenyl)-3,4-diphenyl-5-(hydroxymethyl)furan-2(5H)-
one (4d) (Table 2, Entry 4)
13C NMR (125 MHz, CDCl3):  = 82.6, 122.6, 125.8, 125.9 (tet), 127.0,
127.8, 128.2, 128.6, 128.9, 129.1, 129.3, 129.4, 130.2, 130.7, 131.5,
138.8, 158.9, 172.1.
Yield: 184.7 mg (49%); white solid; mp 155.1–157.0 °C; Rf = 0.28 (hex-
ane/EtOAc, 2:1).
MS (EI): m/z (%) = 380 (30) [M+], 361 (3), 352 (2), 275 (5), 208 (8), 207
(60), 179 (100), 178 (53), 145 (7), 126 (4), 105 (5), 77 (4), 51 (3).
HRMS (ESI): m/z [M+] calcd for C23H15F3O2: 380.1024; found:
IR (KBr): 3434, 3056, 3024, 2925, 2876, 1755 (C=O), 1492, 1176, 1005,
696 cm–1
.
1H NMR (500 MHz, CDCl3):  = 2.38 (t, J = 7.0 Hz, 1 H), 4.20–4.22 (m, 2
380.1024.
H), 6.93 (d, J = 7.0 Hz, 2 H), 7.11 (d, J = 8.5 Hz, 2 H), 7.22–7.38 (m, 10
H).
3,4-Diphenyl-5-hydroxymethyl-5-[4-(trifluoromethyl)phenyl]-
furan-2(5H)-one (4e) (Table 2, Entry 5)
13C NMR (125 MHz, CDCl3):  = 63.8, 90.6, 127.1, 127.9, 128.0, 128.2,
Yield: 168.3 mg (41%); white solid; mp 143.7–145.2 °C; Rf = 0.28 (hex-
128.6, 128.7, 129.1, 131.4, 133.6, 134.6, 162.3, 172.3.
ane/EtOAc, 2:1).
MS (EI): m/z (%) = 376 (3) [M+], 346 (65), 345 (35), 312 (25), 283 (6),
265 (8), 241 (6), 207 (50), 179 (70), 178 (50), 139 (43), 105 (23), 83
(100), 69 (20), 57 (13).
IR (KBr): 3434, 3056, 3024, 2925, 2876, 1758 (C=O), 1326, 1170, 1005,
843 cm–1
.
1H NMR (500 MHz, CDCl3):  = 2.57 (dd, J = 9.0, 6.0 Hz, 1 H), 4.20–4.30
(m, 2 H), 6.95 (d, J = 7.5 Hz, 2 H), 7.22–7.40 (m, 10 H), 7.58 (d, J = 8.5
Hz, 2 H).
HRMS (ESI): m/z [M+] calcd for C23H17ClO3: 376.0866; found:
376.0871.
1
(E)-1-(4-Chlorophenyl)-2,3-diphenyl-2-propen-1-one [(E)-5d]
13C NMR (125 MHz, CDCl3):  = 64.0, 90.8, 123.7 (q, JC–F = 270.6 Hz),
(Table 2, Entry 4)6c
125.4 (q, 3JC–F = 3.6 Hz), 126.1, 126.9, 128.1, 128.2, 128.3, 128.6, 128.9,
129.1, 129.4, 130.7 (q, 2JC–F = 32.1 Hz), 131.3, 139.2, 162.0, 172.3.
Yield: 9.3 mg (2.9%); white solid; mp 89.3–90.1 °C; Rf = 0.26 (hex-
MS (EI): m/z (%) = 410 (3) [M+], 380 (35), 379 (20), 352 (4), 281 (2),
265 (4), 235 (15), 207 (12), 173 (62), 145 (27), 126 (5), 105 (6), 83
(100), 69 (15), 60 (10).
HRMS (ESI): m/z [M+] calcd for C24H17F3O3: 410.1130; found:
410.1130.
ane/EtOAc, 20:1).
IR (KBr): 3054, 3025, 1647 (C=O), 1592, 1443, 1257, 1087, 1013 cm–1
1H NMR (500 MHz, CDCl3):  = 7.09 (d, J = 7.0 Hz, 2 H), 7.19 (t, J = 7.5
Hz, 2 H), 7.20–7.27 (m, 4 H), 7.31–7.37 (m, 3 H), 7.40 (d, J = 7.5 Hz, 2
H), 7.78 (d, J = 8.0 Hz, 2 H).
.
13C NMR (125 MHz, CDCl3):  = 128.0, 128.3, 128.6, 128.8, 129.1,
129.6, 130.4, 131.1, 134.6, 136.2, 136.4, 138.5, 140.2, 140.4, 196.3.
MS (EI): m/z (%) = 321 (10) [M + 3+], 320 (48) [M + 2+], 319 (44) [M +
1+], 318 (M+, 100), 317 (37), 283 (57), 201 (12), 180 (12), 179 (72), 178
(79), 177 (13), 176 (16), 152 (14), 141 (24), 139 (77), 111 (19).
(E)-2,3-Diphenyl-1-[4-(trifluoromethyl)phenyl]-2-propen-1-one
[(E)-5e] (Table 2, Entry 5)6c
Yield: 13.0 mg (3.7%); white solid; mp 116.1–117.2 °C; Rf = 0.17 (hex-
ane/EtOAc, 30:1).
IR (KBr): 3052, 1650 (C=O), 1493, 1443, 1405, 1332, 1255, 1167, 1142,
HRMS (ESI): m/z [M+] calcd for C21H15ClO: 318.0811; found: 318.0810.
1108, 1069, 1016 cm–1
.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–K

H
T. Morimoto et al.
Special Topic
Synthesis
1H NMR (500 MHz, CDCl3):  = 7.09 (d, J = 8.0 Hz, 2 H), 7.16–7.21 (m, 2
H), 7.22–7.28 (m, 4 H), 7.33–7.40 (m, 3 H), 7.70 (d, J = 8.0 Hz, 2 H),
7.91 (d, J = 8.0 Hz, 2 H).
MS (EI): m/z (%) = 372 (3) [M+], 342 (50), 341 (38), 314 (5), 252 (8),
207 (22), 178 (100), 135 (88), 107 (30), 77 (38), 57 (18).
HRMS (ESI): m/z [M+] calcd for C24H20O4: 372.1362; found: 372.1366.
13C NMR (125 MHz, CDCl3):  = 123.7 (q, 1JC–F = 273 Hz), 125.3 (q, 3JC–F
=
1.5 Hz), 128.2, 128.3, 128.8, 128.9, 129.4, 129.6, 129.8, 130.5, 133.3 (q,
(E)-2,3-Diphenyl-1-(3-methoxyphenyl)-2-propen-1-one [(E)-5f]
2JC–F = 32.6 Hz), 134.4, 135.9, 140.3, 141.5, 141.9, 196.4.
(Table 2, Entry 6)6c
MS (EI): m/z (%) = 353 (11) [M + 1+], 352 (36) [M+], 351 (11), 341 (11),
295 (12), 257 (13), 256 (16), 255 (12), 237 (15), 236 (32), 221 (26),
180 (19), 179 (71), 178 (86), 177 (22), 176 (21), 173 (45), 152 (38),
149 (31), 145 (51), 137 (71), 136 (49), 127 (53), 123 (50), 121 (52),
109 (53), 95 (100), 82 (85), 57 (80).
Yield: 4.6 mg (1.5%); white solid; mp 88.4–89.5 °C; Rf = 0.27 (hex-
ane/EtOAc, 10:1).
IR (KBr): 3057, 2923, 2852, 2362, 1653 (C=O), 1597, 1495, 1443, 1269
cm–1
.
1H NMR (500 MHz, CDCl3):  = 3.82 (s, 3 H), 7.06–7.10 (m, 3 H), 7.16–
7.23 (m, 3 H), 7.25–7.29 (m, 3 H), 7.32–7.38 (m, 5 H), 7.44 (d, J = 7.0
Hz, 1 H).
13C NMR (125 MHz, CDCl3):  = 55.4, 114.1, 118.6, 122.5, 126.3, 127.9,
128.2, 128.8, 128.9, 129.2, 129.6, 130.3, 134.7, 136.4, 139.4, 140.1,
140.7, 159.5, 197.3.
MS (EI): m/z (%) = 315 (13) [M + 1+], 314 (59) [M+], 197 (40), 179 (32),
178 (65), 177 (11), 176 (13), 152 (16), 136 (22), 135 (100), 108 (19),
107 (83), 92 (51), 86 (48), 84 (73), 77 (90), 69 (40).
HRMS (ESI): m/z [M+] calcd for C22H15F3O: 352.1075; found: 352.1072.
(Z)-2,3-Diphenyl-1-[4-(trifluoromethyl)phenyl]-2-propen-1-one
[(Z)-5e] (Table 2, Entry 5)6c
Yield: 18.7 mg (5.3%); white solid; mp 105.3–107.2 °C; Rf = 0.26 (hex-
ane/EtOAc, 30:1).
IR (KBr): 3069, 1672 (C=O), 1580, 1497, 1450, 1412, 1325, 1228, 1170,
1124, 1067, 1015 cm–1
.
1H NMR (500 MHz, CDCl3):  = 7.14–7.22 (m, 3 H), 7.24–7.28 (m, 3 H),
7.29–7.39 (m, 3 H), 7.44 (d, J = 7.5 Hz, 2 H), 7.61 (d, J = 8.5 Hz, 2 H),
8.07 (d, J = 8.0 Hz, 2 H).
13C NMR (125 MHz, CDCl3):  = 123.5 (q, 1JC–F = 273 Hz), 125.8 (q, 3JC–F
= 3.8 Hz), 126.4, 128.4, 128.5, 128.6, 128.8, 129.0, 129.9, 131.0, 134.6
(q, 2JC–F = 32.6 Hz), 135.1, 137.5, 138.9, 140.2, 198.3.
HRMS (ESI): m/z [M+] calcd for C22H18O2: 314.1307; found: 314.1307.
(Z)-2,3-Diphenyl-1-(3-methoxyphenyl)-2-propen-1-one [(Z)-5f]
(Table 2, Entry 6)6c
Yield: 12.0 mg (3.8%); white solid; mp 71.2–72.8 °C; Rf = 0.29 (hex-
ane/EtOAc, 10:1).
MS (EI): m/z (%) = 353 (15) [M + 1+], 352 (57) [M+], 351 (21), 219 (10),
207 (12), 181 (12), 180 (16), 179 (95), 178 (100), 177 (43), 176 (35),
175 (11), 174 (11), 173 (63), 152 (26), 151 (19), 146 (11), 145 (67),
133 (40), 131 (21), 126 (15), 125 (16), 121 (11), 119 (21), 103 (28),
102 (22), 101 (24), 95 (20), 89 (45), 88 (42), 87 (43), 77 (25), 75 (35),
73 (41), 72 (20), 69 (41), 59 (41), 58 (36), 57 (29).
IR (KBr): 3056, 3024, 2938, 2835, 1666 (C=O), 1594, 1580, 1484, 1429,
1261, 1037 cm–1
.
1H NMR (500 MHz, CDCl3):  = 3.80 (s, 3 H), 7.01–7.05 (m, 1 H), 7.14–
7.25 (m, 5 H), 7.27–7.37 (m, 5 H), 7.46 (d, J = 7.5 Hz, 2 H), 7.53–7.57
(m, 2 H).
13C NMR (125 MHz, CDCl3):  = 55.3, 113.0, 120.4, 122.8, 126.3, 128.0,
128.1, 128.4, 128.8, 129.7, 130.0, 135.3, 137.6, 137.9, 140.8, 159.8,
199.1.
MS (EI): m/z (%) = 315 (40) [M + 1+], 314 (100) [M+], 286 (18), 236
(14), 198 (15), 197 (95), 180 (13), 179 (94), 178 (96), 177 (40), 176
(47), 166 (10), 152 (47), 151 (25), 150 (10), 136 (37), 135 (98), 126
(14), 108 (25), 107 (95), 102 (20), 92 (94), 77 (95), 69 (73).
HRMS (ESI): m/z [M+] calcd for C22H15F3O: 352.1075; found: 352.1076.
3,4-Diphenyl-5-(3-methoxyphenyl)furan-2(5H)-one (3f) (Table 2,
Entry 6)10
Yield: 35.6 mg (10%); colorless liquid; Rf = 0.42 (hexane/EtOAc, 2:1).
IR (neat): 2921, 2851, 1755 (C=O), 1599, 1450, 1165 cm–1
.
1H NMR (500 MHz, CDCl3):  = 3.68 (s, 3 H), 6.15 (s, 1 H), 6.73–7.39
(m, 14 H).
HRMS (ESI): m/z [M+] calcd for C22H18O2: 314.1307; found: 314.1310.
13C NMR (125 MHz, CDCl3):  = 55.3, 70.6, 83.5, 113.2, 114.6, 120.0,
127.5, 128.3, 128.5, 128.7, 129.0, 129.4, 129.8, 136.2, 159.2, 159.8,
172.4.
MS (EI): m/z (%) = 342 (25) [M+], 314 (3), 285 (4), 252 (11), 237 (7),
207 (18), 178 (100), 152 (25), 135 (28), 107 (26), 77 (33), 57 (43).
3,4-Diphenyl-5-(2-methoxyphenyl)furan-2(5H)-one (3g) (Table 2,
Entry 7)10
Yield: 40.1 mg (12%); colorless liquid; Rf = 0.43 (hexane/EtOAc, 2:1).
IR (neat): 2921, 2851, 1752 (C=O), 1690, 1657, 1158 cm–1
.
1H NMR (500 MHz, CDCl3):  = 3.75 (s, 3 H), 6.73 (s, 1 H), 6.80–7.40
(m, 14 H).
HRMS (ESI): m/z [M+] calcd for C23H18O3: 342.1256; found: 342.1256.
13C NMR (125 MHz, CDCl3):  = 55.6, 70.6, 111.2, 120.9, 122.9, 126.1,
127.5, 128.5, 128.7, 129.0, 129.3, 129.4, 156.1, 159.6, 173.0.
MS (EI): m/z (%) = 342 (13) [M+], 314 (3), 281 (2), 252 (4), 236 (20),
207 (8), 178 (80), 152 (22), 135 (23), 105 (13), 83 (100), 77 (33), 51
(31).
3,4-Diphenyl-5-(hydroxymethyl)-5-(3-methoxyphenyl)furan-
2(5H)-one (4f) (Table 2, Entry 6)
Yield: 196.3 g (53%); colorless liquid; Rf = 0.26 (hexane/EtOAc, 2:1).
IR (neat): 3433, 3056, 3022, 2933, 2837, 1752 (C=O), 1600, 1490,
1264, 1007, 786 cm–1
.
HRMS (ESI): m/z [M+] calcd for C23H18O2: 342.1256; found: 342.1254.
1H NMR (500 MHz, CDCl3):  = 2.49 (t, J = 7.0 Hz, 1 H), 3.71 (s, 3 H),
4.24 (d, J = 6.0 Hz, 2 H), 6.72–6.76 (m, 2 H), 6.88 (dd, J = 8.0, 2.0 Hz, 1
H), 6.97 (d, J = 7.0 Hz, 2 H), 7.22–7.39 (m, 9 H).
13C NMR (125 MHz, CDCl3):  = 64.1, 90.9, 111.4, 114.2, 118.0, 127.9,
128.1, 128.4, 128.5, 128.7, 129.1, 129.2, 129.3, 131.8, 136.6, 159.5,
162.4, 172.4.
3,4-Diphenyl-5-hydroxymethyl-5-(2-methoxyphenyl)furan-
2(5H)-one (4g) (Table 2, Entry 7)
Yield: 16.4 mg (4%); white solid; mp 62.5–63.9 °C; Rf = 0.20 (hex-
ane/EtOAc, 2:1).
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–K

I
T. Morimoto et al.
Special Topic
Synthesis
IR (KBr): 3409, 2917, 2849, 1744 (C=O), 1598, 1180, 1076, 751 cm–1
.
1H NMR (500 MHz, CDCl3):  = 2.52 (br, 1 H), 3.77 (s, 3 H), 3.79 (s, 3 H),
4.19–4.29 (m, 2 H), 6.76–7.34 (m, 13 H).
1H NMR (500 MHz, CDCl3):  = 2.19 (t, J = 7.5 Hz, 1 H), 3.51 (s, 3 H),
4.19–4.35 (m, 2 H), 6.78 (d, J = 5.0 Hz, 2 H), 6.84 (d, J = 10.0 Hz, 1 H),
6.91 (m, 1 H), 7.12–7.33 (m, 10 H).
13C NMR (125 MHz, CDCl3):  = 55.4, 64.3, 89.6, 112.0, 120.8, 122.4,
128.0, 128.2, 128.3, 128.6, 128.7, 129.0, 129.2, 129.4, 130.6, 132.2,
158.3, 160.6, 172.7.
13C NMR (125 MHz, CDCl3):  = 29.2, 31.7, 55.1, 64.0, 69.7, 90.8, 113.6,
114.2, 122.1, 124.0, 125.9, 126.8, 128.6, 128.7, 129.9, 130.0, 130.6,
135.6, 159.6, 160.1, 160.7, 173.0.
HRMS (ESI): m/z [M + Na+] calcd for C25H22NaO5: 425.1365; found:
425.1365.
MS (EI): m/z (%) = 372 (1) [M+], 342 (21), 341 (28), 314 (4), 252 (8),
207 (8), 178 (80), 135 (56), 107 (13), 83 (100), 57 (45).
HRMS (ESI): m/z [M+] calcd for C24H20O4: 372.1362; found: 372.1371.
3,4,5-Tris(4-methoxyphenyl)furan-2(5H)-one (7b) (Table 3, Entry
1)10
Yield: 53.1 mg (13%); colorless liquid; Rf = 0.19 (hexane/EtOAc, 2:1).
IR (neat): 3003, 2933, 2837, 1747 (C=O), 1606, 1513, 1457, 1252,
2,3-Diphenyl-1-(2-methoxyphenyl)-2-propen-1-one [(E)- and (Z)-
1177, 1029, 833 cm–1
.
5g] (Table 2, Entry 7)6c
Yield: 4.1 mg (1.3%); colorless oil; Rf = 0.21; (hexane/EtOAc, 10:1).
1H NMR (500 MHz, CDCl3):  = 3.74 (s, 3 H, E-isomer), 3.76 (s, 3 H, Z-
isomer).
13C NMR (125 MHz, CDCl3):  = 55.5, 55.6, 111.2, 111.9, 120.3, 120.5,
127.7, 128.1, 128.4, 128.5, 128.9, 129.3, 130.0, 130.6, 131.5, 132.0,
134.6, 150.0, 136.0, 136.1, 138.2, 141.7, 142.2, 144.3, 157.0, 159.4,
197.6, 198.0.
1H NMR (500 MHz, CDCl3):  = 3.74 (s, 3 H), 3.77 (s, 3 H), 3.83 (s, 3 H),
6.18 (s, 1 H), 6.71 (d, J = 9.0 Hz, 2 H), 6.84 (d, J = 9.0 Hz, 2 H), 6.91 (d,
J = 9.0 Hz, 2 H), 7.10 (d, J = 9.0 Hz, 2 H), 7.22 (d, J = 9.0 Hz, 2 H), 7.44 (d,
J = 8.5 Hz, 2 H).
13C NMR (125 MHz, CDCl3):  = 55.13, 55.17, 55.2, 83.1, 114.0, 114.1,
114.2, 122.5, 122.7, 124.0, 127.2, 127.5, 128.7, 129.1, 129.7, 130.0,
130.2, 130.7, 131.1, 149.9, 157.6, 160.1, 160.5, 172.4.
HRMS (ESI): m/z [M + Na +] calcd for C25H22NaO5: 425.1365; found:
425.1365.
(Z)-2,3-Diphenyl-1-(2-methoxyphenyl)-2-propen-1-one [(Z)-5g]
(Table 2, Entry 7)6c
5-(Hydroxymethyl)-3,4,5-tris(4-methoxyphenyl)furan-2(5H)-one
(8b) (Table 3, Entry 1)
Yield: 2.8 mg (0.9%); white solid; mp 91.4–92.5 °C; Rf = 0.21; (hex-
ane/EtOAc, 10:1).
Yield: 238.7 mg (55%); colorless liquid; Rf = 0.11 (hexane/EtOAc, 2:1).
IR (KBr): 3021, 1650 (C=O), 1595, 1483, 1285, 1248, 1213, 1162, 1021,
757, 727, 694, 673, 566, 523, 514 cm–1
.
IR (neat): 3451, 2958, 2934, 2837, 1747 (C=O), 1607, 1513, 1253,
1175, 1031, 833 cm–1
.
1H NMR (500 MHz, CDCl3):  = 3.75 (s, 3 H), 6.82 (d, J = 8.0 Hz, 1 H),
6.90 (t, J = 7.0 Hz, 1 H), 7.00 (s, 1 H), 6.82 (d, J = 8.0 Hz, 1 H), 6.90 (t, J =
7.0 Hz, 2 H), 7.14–7.33 (m, 5 H), 7.39 (t, J = 7.0 Hz, 1 H), 7.43–7.45 (m,
2 H), 7.85 (d, J = 9.0 Hz, 1 H).
1H NMR (500 MHz, CDCl3):  = 2.35–2.37 (m, 1 H), 3.77 (s, 3 H), 3.79
(s, 3 H), 3.82 (s, 3 H), 4.14–4.27 (m, 2 H), 6.78 (d, J = 9.0 Hz, 4 H), 6.86–
6.88 (m, 4 H), 7.18 (d, J = 9.0 Hz, 2 H), 7.37 (d, J = 8.5 Hz, 2 H).
13C NMR (125 MHz, CDCl3):  = 55.5, 111.9, 120.3, 126.8, 127.6, 127.8,
128.2, 128.5, 128.8, 132.0, 134.5, 136.0, 138.2, 144.3, 159.4, 197.6.
MS (EI): m/z (%) = 316 (3) [M + 2+], 315 (23) [M + 1+], 314 (94) [M+],
178 (22), 135 (100), 92 (13), 77 (20), 51 (4).
13C NMR (125 MHz, CDCl3):  = 55.02, 55.06, 55.14, 64.0, 90.4, 113.5,
113.9, 114.0, 122.1, 123.2, 123.9, 126.4, 127.2, 127.3, 129.9, 130.5,
159.4, 159.6, 160.0, 160.5, 172.8.
HRMS (ESI): m/z [M + Na +] calcd for C26H24NaO5: 455.1471; found:
455.1471.
HRMS (ESI): m/z [M+] calcd for C22H18O2: 314.1307; found: 314.1305.
3,4-Bis(4-methoxyphenyl)-5-[4-(trifluoromethyl)phenyl]furan-
3,4-Bis(4-methoxyphenyl)-5-phenylfuran-2(5H)-one (7a) (Table 3,
2(5H)-one (7e) (Table 3, Entry 3)10
Entry 2)10
Yield: 48.0 mg (11%); colorless liquid; Rf = 0.28 (hexane/EtOAc, 2:1).
Yield: 42.1 mg (11%); colorless liquid; Rf = 0.28 (hexane/EtOAc, 2:1).
IR (neat): 2933, 2837, 1750 (C=O), 1605, 1517, 1253, 1025, 835 cm–1
IR (neat): 2916, 1752 (C=O), 1606, 1507, 1254, 1124, 834 cm–1
.
.
1H NMR (500 MHz, CDCl3):  = 3.73 (s, 3 H), 3.81 (s, 3 H), 6.28 (s, 1 H),
6.72 (d, J = 8.5 Hz, 2 H), 6.89 (d, J = 9.0 Hz, 2 H), 7.09 (d, J = 9.0 Hz, 2 H),
7.40–7.43 (m, 4 H), 7.56 (d, J = 8.0 Hz, 2 H).
13C NMR (125 MHz, CDCl3):  = 55.2, 55.3, 82.3, 114.1, 114.3, 122.0,
123.0, 125.1, 125.9 (q, JC-F = 3.5 Hz), 128.0, 129.8, 130.7, 139.4, 157.0,
160.8, 172.7.
1H NMR (500 MHz, CDCl3):  = 3.74 (s, 3 H), 3.84 (s, 3 H), 6.21 (s, 1 H),
6.72 (d, J = 9.5 Hz, 2 H), 6.91 (d, J = 8.5 Hz, 2 H), 7.11 (d, J = 9.0 Hz, 2 H),
7.29–7.34 (m, 5 H), 7.45 (d, J = 9.5 Hz, 2 H).
13C NMR (125 MHz, CDCl3):  = 55.16, 55.21, 83.4, 114.0, 122.4, 123.4,
124.9, 127.7, 128.9, 129.3, 129.9, 130.7, 135.3, 157.4, 159.8, 160.6,
173.0.
HRMS (ESI): m/z [M + Na +] calcd for C25H19F3NaO4: 463.1133; found:
463.1133.
HRMS (ESI): m/z [M + Na+] calcd for C24H20NaO4: 395.1259; found:
395.1259.
3,4-Bis(4-methoxyphenyl)-5-hydroxymethyl-5-[4-(trifluoro-
methyl)phenyl]furan-2(5H)-one (8e) (Table 3, Entry 3)
3,4-Bis(4-methoxyphenyl)-5-hydroxymethyl-5-phenylfuran-
2(5H)-one (8a) (Table 3, Entry 2)
Yield: 166.1 mg (35%); colorless liquid; Rf = 0.14 (hexane/EtOAc, 2:1).
Yield: 196.4 mg (49%); colorless liquid; Rf = 0.14 (hexane/EtOAc, 2:1).
IR (neat): 2916, 1752 (C=O), 1606, 1507, 1254, 1124, 834 cm–1
.
IR (neat): 3451, 2934, 2837, 1751 (C=O), 1606, 1516, 1251, 1175, 828
cm–1
.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–K

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T. Morimoto et al.
Special Topic
Synthesis
1H NMR (500 MHz, CDCl3):  = 2.40 (t, J = 10.0 Hz, 1 H), 3.77 (s, 3 H),
3.82 (s, 3 H), 4.24 (d, J = 6.5 Hz, 2 H), 6.77 (d, J = 9.0 Hz, 2 H), 6.84–6.89
(m, 4 H), 7.33–7.36 (m, 4 H), 7.59 (d, J = 8.5 Hz, 2 H).
HRMS (ESI): m/z [M+] calcd for C25H16F6O3: 478.1004; found:
478.1004.
13C NMR (125 MHz, CDCl3):  = 55.1, 55.2, 64.3, 90.4, 113.6, 114.4,
3,4-Bis[4-(trifluoromethyl)phenyl]-5-hydroxymethyl-5-(4-meth-
oxyphenyl)furan-2(5H)-one (11b) (Table 3, Entry 5)
121.6, 123.7 (q, 1JC–F = 270.6 Hz), 124.8, 125.4 (q, 3JC–F = 3.6 Hz), 126.3,
2
127.1, 129.8, 130.5, 135.7 (q, JC–F = 32.6 Hz), 139.7, 159.6, 160.2,
Yield: 291.8 mg (57%); white solid; mp 80.5–81.7 °C; Rf = 0.22 (hex-
172.5.
ane/EtOAc, 2:1).
HRMS (ESI): m/z [M + Na +] calcd for C26H21F3NaO5: 493.1239; found:
IR (KBr): 3434, 2916, 1757 (C=O), 1613, 1514, 1325, 1257, 828 cm–1
.
493.1239.
1H NMR (500 MHz, CDCl3):  = 2.63 (br, 1 H), 3.83 (s, 3 H), 4.16–4.28
(m, 2 H), 6.89 (d, J = 9.5 Hz, 2 H), 7.05 (d, J = 8.0 Hz, 2 H), 7.09 (d, J = 8.5
Hz, 2 H), 7.49 (dd, J = 21.5, 8.5 Hz, 4 H), 7.58 (d, J = 8.5 Hz, 2 H).
3,4-Bis[4-(trifluoromethyl)phenyl]-5-phenylfuran-2(5H)-one
(10a) (Table 3, Entry 5)10
13C NMR (125 MHz, CDCl3):  = 55.3, 63.6, 91.2, 114.3, 123.9 (q, 1JC–F
272.5 Hz), 124.0 (q, JC–F = 271.3 Hz), 125.3 (q, JC–F = 3.8 Hz), 125.7,
125.8 (q, 3JC–F = 3.8 Hz), 127.0, 128.0, 128.8, 129.5, 131.0 (q, 2JC–F = 32.5
Hz), 131.6 (q, 2JC–F = 32.5 Hz), 131.7, 132.5, 135.0, 160.1, 162.9, 171.7.
=
Yield: 23.8 mg (5%); colorless liquid; Rf = 0.42 (hexane/EtOAc, 2:1).
IR (neat): 2920, 1763 (C=O), 1324, 1168, 1128, 1018 cm–1
1H NMR (500 MHz, CDCl3):  = 6.28 (s, 1 H), 7.18 (d, J = 8.0 Hz, 2 H),
7.36–7.54 (m, 6 H), 7.58 (d, J = 8.0 Hz, 3 H), 7.64 (d, J = 8.5 Hz, 2 H).
1
3
.
MS (EI): m/z (%) = 508 (1) [M+], 478 (100), 477 (90), 421 (13), 320 (5),
314 (72), 246 (8), 225 (6), 176 (3), 135 (100), 57 (19).
HRMS (ESI): m/z [M+] calcd for C26H18F6O4: 508.1109; found:
508.1109.
13C NMR (125 MHz, CDCl3):  = 69.6, 83.9, 125.7 (q, JC-F = 3.5 Hz), 126.0
(q, JC-F = 3.5 Hz), 127.5, 128.6, 128.9, 129.1, 129.2, 129.7, 129.8, 136.0,
158.8, 171.4.
MS (EI): m/z (%) = 448 (32) [M+], 447 (8), 343 (6), 314 (35), 295 (9),
210 (18), 173 (100), 134 (79), 105 (97), 77 (30).
5-(Hydroxymethyl)-3,4,5-tris[4-(trifluoromethyl)phenyl]furan-
2(5H)-one (11e) (Table 3, Entry 6)
HRMS (ESI): m/z [M+] calcd for C24H14F6O2: 448.0898; found:
448.0897.
Yield: 142.1 mg (26%); white solid; mp 71.3–72.5 °C; Rf = 0.33 (hex-
ane/EtOAc, 2:1).
IR (KBr): 3448, 2936, 1760 (C=O), 1617, 1327, 1123, 1069, 844 cm–1
.
3,4-Bis[4-(trifluoromethyl)phenyl]-5-hydroxymethyl-5-phenyl-
1H NMR (500 MHz, CDCl3):  = 2.88 (br, 1 H), 4.25 (qd, J = 17.5, 12.5,
5.0 Hz, 2 H), 7.11 (d, J = 8.0 Hz, 2 H), 7.26–7.27 (m, 2 H), 7.47 (dd, J =
32.5, 8.5 Hz, 4 H), 7.63 (dd, J = 14.5, 8.0 Hz, 4 H).
furan-2(5H)-one (11a) (Table 3, Entry 5)
Yield: 199.5 mg (42%); colorless liquid; Rf = 0.33 (hexane/EtOAc, 2:1).
IR (neat): 3403, 3081, 2920, 1753 (C=O), 1617, 1328, 1166, 1123, 826
1
cm–1
.
13C NMR (125 MHz, CDCl3):  = 63.8, 91.2, 122.4 (q, JC–F = 271.3 Hz),
122.46 (q, 1JC–F = 271.3 Hz), 122.51 (q, 1JC–F = 270.9 Hz), 125.2 (q, 3JC–F
=
1H NMR (500 MHz, CDCl3):  = 2.54 (dd, J = 8.5, 5.0 Hz, 1 H), 4.26 (qd,
J = 21.0, 12.5, 9.0 Hz, 2 H), 7.05 (d, J = 8.0 Hz, 2 H), 7.15–7.17 (m, 2 H),
7.36–7.40 (m, 3 H), 7.49 (dd, J = 24.0, 8.0 Hz, 4 H), 7.59 (d, J = 8.0 Hz, 2
H).
3.8 Hz), 125.8 (q, 3JC–F = 3.6 Hz), 125.8, 126.1 (q, 3JC–F = 3.5 Hz), 128.3,
2
2
128.7, 129.4, 129.3, 129.5, 130.6 (q, JC–F = 32.5 Hz), 131.1 (q, JC–F
=
2
27.5 Hz), 131.6 (q, JC–F = 30.0 Hz), 131.9, 132.0, 134.4, 138.1, 162.2,
171.4.
13C NMR (125 MHz, CDCl3):  = 63.6, 91.4, 123.6 (q, JC–F = 270.0 Hz),
1
MS (EI): m/z (%) = 546 (4) [M+], 516 (90), 497 (20), 315 (100), 314 (25),
246 (12), 173 (61), 145 (17), 115 (3), 91 (2).
HRMS (ESI): m/z [M+] calcd for C26H15F9O3: 546.0877; found:
123.7 (q, 1JC–F = 271.3 Hz), 125.3 (q, 3JC–F = 3.8 Hz), 125.5, 125.9 (q, 3JC–F
2
= 3.6 Hz), 127.9, 128.8, 129.0, 129.3, 129.5, 130.7 (q, JC–F = 31.3 Hz),
131.6 (q, 2JC–F = 32.5 Hz), 132.4, 134.0, 134.9, 162.9, 171.7.
546.0877.
HRMS (ESI): m/z [M + Na +] calcd for C25H16F6NaO3: 501.0901; found:
501.0901.
Conflict of Interest
3,4-Bis[4-(trifluoromethyl)phenyl]-5-(4-methoxyphenyl)furan-
2(5H)-one (10b) (Table 3, Entry 4)10
The authors declare no conflict of interest.
Yield: 28.2 mg (6%); colorless liquid; Rf = 0.36 (hexane/EtOAc, 2:1).
IR (neat): 3059, 2925, 2853, 1757 (C=O), 1612, 1548, 1324, 1168,
Acknowledgment
1068 cm–1
.
1H NMR (500 MHz, CDCl3):  = 3.80 (s, 3 H), 6.25 (s, 1 H), 6.88 (d, J =
9.0 Hz, 2 H), 7.19 (t, J = 9.0 Hz, 4 H), 7.51 (d, J = 5.0 Hz, 2 H), 7.58 (d, J =
8.0 Hz, 2 H), 7.64 (d, J = 10.0 Hz, 2 H).
We wish to thank Ms. Yoshiko Nishikawa and Ms. Mieko Yamagaki,
and Mr. Shouhei Katao for assistance in obtaining HRMS and X-ray
crystallographic data, respectively.
13C NMR (125 MHz, CDCl3):  = 55.3, 63.6, 91.2, 114.3, 123.6 (q, 1JC–F
=
270.6 Hz), 123.7 (q, 1JC–F = 270.5 Hz), 125.3 (q, 3JC–F = 3.6 Hz), 125.672,
126.6 (q, 3JC–F = 3.6 Hz), 127.0, 127.7, 128.8, 129.5, 130.7 (q, 2JC–F = 32.3
Hz), 131.3 (q, 2JC–F = 32.1 Hz), 131.7, 132.5, 135, 160.1, 162.9, 171.7
Supporting Information
Supporting information for this article is available online at
MS (EI): m/z (%) = 478 (45) [M+], 459 (8), 421 (6), 314 (35), 295 (8),
246 (4), 225 (3), 135 (100), 71(13).
https://doi.org/10.1055/a-1468-8377. Su
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© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–K

K
T. Morimoto et al.
Special Topic
Synthesis
References
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=
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© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–K