Synthesis of (: Z)-β-halo α,β-unsaturated carbonyl systems via the combination of halotrimethylsilane and tetrafluoroboric acid

Article abstract of DOI:10.1039/c8ob02110d

A convenient and broadly applicable method for the hydrohalogenation of ynones is described, by the combination of halotrimethylsilanes and tetrafluoroboric acid. Practically, one equivalent of HX (Br?nsted acid) and BF₃ (Lewis acid) is smoothly generated, which activates the carbonyl compounds. Through this protocol, 42 examples of (Z)-β-halovinyl carbonyl compounds (Cl, Br and I) were obtained, in good yields and high stereoselectivity having 2-MeTHF as a solvent.

Full text of DOI:10.1039/c8ob02110d

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Synthesis of (Z)-β-halo α,β-unsaturated carbonyl
systems via the combination of halotrimethylsilane
and tetrafluoroboric acid†
Cite this: Org. Biomol. Chem., 2019,
17, 519
Vitor A. F. da Silva, a Gustavo P. da Silva,a Bianca T. Matsuo,a Akbar Ali,a,b
Rebecca L. Davis, *c Julio Zukerman-Schpector,a Arlene G. Corrêa a and
a
Márcio W. Paixão
*
A convenient and broadly applicable method for the hydrohalogenation of ynones is described, by the
combination of halotrimethylsilanes and tetrafluoroboric acid. Practically, one equivalent of HX (Brønsted
acid) and BF3 (Lewis acid) is smoothly generated, which activates the carbonyl compounds. Through this
protocol, 42 examples of (Z)-β-halovinyl carbonyl compounds (Cl, Br and I) were obtained, in good yields
and high stereoselectivity having 2-MeTHF as a solvent.
Received 28th August 2018,
Accepted 11th December 2018
DOI: 10.1039/c8ob02110d
rsc.li/obc
lyzed addition of acid chlorides to terminal alkynes for the syn-
Introduction
thesis of β-chloroalkenyl ketones.8
β-Halovinyl ketones are valuable and versatile synthetic inter-
On the other hand, catalytic methodologies employing
mediates for the synthesis of precious bio-active molecules.1 Lewis acids (AlCl3 and GaCl3) have also been described for the
Among them, β-chloro-α,β-unsaturated ketones have been widely synthesis of these versatile synthetic scaffolds, employing the
used as synthetic precursors in a range of cyclic compounds, e.g. same combination of starting materials.9
furans, pyrazoles, pyridines, cyclic thioethers, chromenones,
thiochromenones and 4-substituted-2-naphthols (Fig. 1).2
In addition to the aforementioned methodologies, an
important and straightforward approach towards the synthesis
Furthermore, Oh and co-workers recently reported the syn- of β-haloenones is the hydrohalogenation of electron deficient
thesis of allenyl ketones and propargyl ketones from stereo- ynones by various halide sources (e.g., HCl/H2O, HCl in
chemically defined β-chlorovinyl ketones under basic conditions.3 organic solvents, SnCl4/H2O, HBr/H2O, AlBr3/H2O and LiBr/
Considering their high synthetic potential, the development of TFA).10 Very recently, Xu, Hammond and their co-workers
new methodologies which provide access to β-chlorovinyl developed a metal-free and stereoselective approach for the
ketones is of great demand.4 The majority of the already
described methodologies for the synthesis of these versatile
building blocks have focused on transition-metal catalyzed
reactions.5
For instance, Tanaka and co-workers reported the rhodium-
catalyzed addition of acyl chlorides to alkynes.6 In a similar
way, Tsuji and co-workers described an iridium-catalyzed
addition of aromatic acid chlorides to terminal alkynes to
form β-chloro-α,β-unsaturated ketones.7 Recently, Li et al. and
Cheng’s group have independently explored the iron(III)-cata-
aCentre of Excellence for Research in Sustainable Chemistry (CERSusChem),
Department of Chemistry, Federal University of São Carlos – UFSCar, São Carlos,
São Paulo, Brazil. E-mail: mwpaixao@ufscar.br
bDepartment of Chemistry, University of Sargodha, 40100, Pakistan
cDepartment of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada.
E-mail: rebecca.davis@umanitoba.ca
†Electronic supplementary information (ESI) available. CCDC 1843637. For ESI
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
c8ob02110d
Fig. 1 Synthetic utility of β-chlorovinyl ketones.
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Table 1 Reaction optimization studies
HBF4·OEt2
(equiv.)
Time
(h)
Yieldb
(%)
Entrya
Solvent
Z/Ec
1d
DCM
DCM
DCM
EtOAc
MeCN
TFE
EtOH
DMSO
0.5
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.6
—
—
—
—
1.6
—
4
4
4
4
6
4
4
24
4
22
20
24
24
24
24
24
24
40
44
60
48
50
55
Traces
Traces
62
66
90
28
28
46
82
60
84
86 : 14
91 : 9
89 : 11
86 : 14
91 : 9
93 : 7
—
2d
3
4
5
6
7
8
9
10
11
12e,k
13f,k
14g,k
15h,k
16i,k
17j,k
—
GVL
90 : 10
99 : 1
87 : 13
84 : 16
80 : 20
85 : 15
90 : 10
89 : 11
68 : 32
2-Me-THF
2-Me-THF
2-Me-THF
2-Me-THF
2-Me-THF
2-Me-THF
2-Me-THF
2-Me-THF
Scheme 1 Strategies to access β-halovinyl ketones: (a) previous meth-
odologies using transition metals or Lewis acid catalysis; (b) strategies
for the hydrohalogenation of ynones via in situ generation of HX; (c) the
combination of halotrimethylsilane and tetrafluoroboric acid.
a Unless otherwise stated, the reactions were carried out using 1a (1.0
equiv.), TMSCl (2.0 equiv.), and HBF4·OEt2 (ranging from 0.5 to 1.6
equiv.) in the mentioned solvent ([c] = 0.375 mol L−1). b Yields were
determined after silica gel chromatography. c The diastereoselective
ratio (Z/E) was determined by the GC-MS analysis of the crude mixture.
d Reaction was carried out using 1.0 equiv. of TMSCl. e Reaction was
carried out using TFA (1.6 equiv.) as a proton source. f Reaction was
performed using BF3·OEt2 (1.6 equiv.) as the Lewis Acid. g Reaction was
performed using BF3·OEt2 (1.6 equiv.) and TFA (1.6 equiv.). h Reaction
was carried out using MeOH (1.6 equiv.) as the proton source. i Under
an argon atmosphere and dry 2-Me-THF. j Using DMPU·HCl (1.6
equiv.) as the HCl source. k The yield was determined by GC-MS.
hydrochlorination or hydrobromination of ynones using an
easily handled DMPU/HX complex.11
However, the majority of these methods show low stereo-
control (the products are usually obtained as mixtures of E and
Z isomers)10 and this has presumably limited their synthetic
application. In addition, some key limitations include the
halogen nature and the synthesis of β-halo α,β-unsaturated
aldehydes.12
Considering the noteworthy need to develop a broadly
applicable method to enable the direct construction of C(sp2)–I,
Br, and Cl bonds in a range of carbonyl derivatives, we herein
wish to report a highly efficient metal-free hydrohalogenation
of ynones and ynals – this new metal-free protocol provides a
general entry for the regio- and stereoselective synthesis
of useful β-halo α,β-unsaturated systems in high yields
(Scheme 1c).
silane and 1.1 equiv. of HBF4·OEt2 were employed (Table 1,
entry 3, 60% yield).
The influence of different solvents on this transformation
was subsequently investigated (entries 4–10). The screening
revealed that the yields were slightly on the lower side using ethyl
acetate, acetonitrile (MeCN) and trifluoroethanol (TFE) compared
to dichloromethane (entry 3 vs. 4, 5 and 6). Additionally, by
employing EtOH or DMSO as a solvent system only traces of the
desired product were observed (entries 7 and 8).
Interestingly, the bio-based solvents e.g. 2-methyl-
tetrahydrofuran (2-Me-THF) and γ-valerolactone (GVL) were
found to be more efficient reaction media for this transform-
Results and discussion
Initially, 4-phenyl-3-butyn-2-one (1a), chlorotrimethylsilane ation, affording the desired product in both higher yields and
and a tetrafluoroboric acid diethyl ether complex were chosen stereoselectivities (entries 9 and 10). Likewise, an increase in
as model substrates to optimize the reaction conditions. The the amount of Lewis acid in 2-Me-THF as the solvent was
reaction was performed using HBF4·OEt2 (0.5 equiv.) with tested and to our delight the final product 4-chloro-4-phenyl-
TMSCl (1 equiv.) as the chloride source and THF as the but-3-en-2-one was isolated in 90% yield and a Z/E ratio of
solvent. The expected product was obtained in 40% isolated 87 : 13 (entry 11).
yield after 4 h (Table 1, entry 1). Next, the optimization was
Encouraged by these results, we further evaluated the reac-
focused on the molar ratio of reactants and the loading of tion performance by changing the acidic partner. However, no
HBF4·OEt2 was increased to 1.1 equiv. (1.1 : 1 ratio of a Lewis improvement was observed in the chemical yield (entries
acid to TMSCl). Consequently, under these conditions, a low 12–15). These results showed that both Brønsted and Lewis
chemical yield was observed (Table 1, entry 2). Moreover, the acids can activate the carbonyl system for the addition event.
chemical yield was improved when 2 equiv. of chlorotrimethyl- Interestingly, when methanol was employed as a proton
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source, the desired product could be obtained with a good Z/E observed when substrates bearing the phenyl ring attached to
ratio; however, a decrease in the chemical yield was observed the carbonyl center (R2) were subjected to the reaction con-
(Table 1, entry 15). Moreover, the influence of moisture on the ditions (product 2d obtained with 95% yield with 91 : 9 Z/E).
reaction media has also been evaluated. When the reaction Furthermore, ynones having an aromatic system decorated
was carried out under inert conditions, the β-chlorovinyl with electron-withdrawing or -donating groups at the para-,
ketone was obtained in a lower chemical yield (Table 1, entry meta- or ortho-positions were found to be well compatible –
16). Thus, this result demonstrates that water plays some role delivering the corresponding products in good to high yields
in the activation of the substrates, even though its presence is with comparable selectivities (see compounds 2e to 2s at
not essential. For a comparison study, the reaction has been Fig. 2). Ynones with the aromatic substituent R2 delivered the
performed using DPMU/HCl in 2-Me-THF as the solvent corresponding products in higher yields when compared to
sytem.11 Under these conditions the desired product was their aliphatic counterparts (compare 2d: 95% vs. 2t: 46% and
obtained in both lower yield and stereoselectivity (Table 1, 2u: 65%) – however, a slight variation in terms of stereocontrol
entry 17).
could be observed. Interestingly, when a trimethylsilylalkynone
With the optimized reaction conditions in hand (Table 1, was subjected to the optimal reaction conditions, the desired
entry 11), we explored the scope and limitation of our protocol product was obtained in 91% yield with a Z/E ratio of 60 : 40
towards a range of ynones. To our satisfaction, the optimized (compound 2v). Surprisingly, subjecting oct-3-yn-2-one to the
reaction conditions were found to be generally applicable for standard reaction conditions delivered product 2w′, which had
substrates having diverse electronic properties. It is worth undergone a double-bond-migration, giving a similar yield
noting that the protocol is amenable for the ynones having a and selectivity (50%, 93 : 7 Z/E) when compared with ynones
number of aliphatic and aromatic structural motifs (Fig. 2, containing alkyl groups at the R1 or R2 positions (2w′ vs. 2t
2a–2x, yield up to 96% and Z/E up to 99 : 1). Initially, ynones and 2u).
decorated with aromatic groups attached to the sp center and
To our delight, the present protocol turned out to be highly
aliphatic substituents at the R2 position delivered the desired chemoselective for product 2x, thus rendering product 2x in
product in good to excellent yields with high stereoselectivity 89% yield and 90 : 10 Z/E – this result therefore indicates that
(compounds 2a to 2c). A similar chemical efficiency was an additional conjugate system did not impact the reaction
Fig. 2 Exploration of the substrate scope. All yields are isolated, the Z/E ratio is determined by 1H NMR from the crude mixture. Reaction conditions:
(I) For chlorination: ynone (1.0 equiv.), TMSCl (2.0 equiv.) and HBF4·OEt2 (1.6 equiv. for a, 2.0 equiv. for b) in MeTHF (0.4 mL) at room temperature for
24 h. (II) For bromination: ynone (1.0 equiv.), TMSBr (2.0 equiv.) and HBF4·OEt2 (2.0 equiv.) in MeTHF (0.4 mL) for 24 h at room temperature. (III) For
iodination: ynone (1.0 equiv.), TMSI (2.0 equiv.) and HBF4·OEt2 (2.0 equiv.) in MeTHF (0.4 mL) for 24 h at −20 °C. (IV) For halogenation of ynals: ynal
(1.0 equiv.), TMSX (X = Cl and Br, 2.0 equiv.) and HBF4·OEt2 (2.0 equiv.) in MeTHF (0.4 mL) at room temperature. cQuantified and characterized after
reduction with NaBH4 (1.2 equiv.) for 1 h at room temperature.
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outcome. Having completed the reaction scope for the ynone,
we turned our attention to a propiolate counterpart – however,
under the optimized reaction conditions the hydrochlorination
of benzyl 3-phenylpropiolate did not occur and all the starting
material was recovered. Thus, this substrate currently rep-
resents a limitation of the described methodology.
To further explore the applicability of our halogenation pro-
tocol, the scope was extended to the bromination of ynones.
Excitingly, the same level of chemical efficiency was observed
without altering the optimized reaction conditions (Fig. 2,
section II). To our delight, significant substituent effects could
not be observed, and the bromination of ynones showed to be
independent of the aromatic or aliphatic nature of R1 in terms
of yield (3a: 80% vs. 3h: 80%), though slight differences in the
Fig. 3 Hydrochlorination of the ynone 1d (a) under microwave
selectivity were observed. In addition, the attachment of an irradiation and (b) a gram scale synthesis.
electron rich or electron poor aromatic system to the sp center
(R1) disclosed no difference in terms of chemical efficiency
(3e: 97% vs. 3f: 98%) – however, a little variation in the stereo-
selectivity was noticed (3e: Z/E 77 : 23 vs. 3f: Z/E 86 : 14).
Moreover, the 3e structure, in particular with regard to the
stereochemistry, was assigned unambiguously by X-ray crystal-
lography (see the ESI†).
Furthermore, we turned our attention toward demonstrat-
ing the potential scalability of this hydrohalogenation
approach. The synthesis of β-chlorovinyl ketones 2d was per-
formed on a gram scale (1.03 g, 5.0 mmol) and the desired
product was isolated – after a simple operational liquid–liquid
It is worth mentioning that a similar behavior was also
experienced regarding the nature of the system attached to the
carbonyl center (R2) (3a: 80% vs. 3g: 82%) – nevertheless, the
aromatic systems responded well in terms of stereoselectivity
(3a: 99 : 1 vs. 3g: 77 : 23). Moreover, compound 3i was obtained
in 89% yield and 95 : 5 Z/E.
We also evaluated our synthetic approach for the iodination
of ynones, which provide β-iodo α,β-unsaturated carbonyl
systems. Since iodotrimethylsilane readily decomposes at
room temperature, the reaction temperature was lowered to
−20 °C. Under these conditions, aromatic ynones delivered the
β-iodo, α,β-unsaturated carbonyl compounds in high yields
(Fig. 2, section III). The electronic nature of the aromatic
system attached to the sp center (R1) varied the yield to a small
extent (4a: 89% vs. 4d: 94% vs. 4e: 86%), however with evident
selectivity distortion. The same trend was experienced for the
different electronic capability of the aromatic system attached
to the sp2 center (R2).
Fig. 4 1H NMR of (a) substrate 1a (blue), (b) the crude product 2a after
workup (green) and (c) compound 2a after chromatography purification
(red) using CDCl3 as the solvent.
Having successfully achieved the hydrohalogenation of a
library of ynones, attention was turned to the application of
aromatic ynals as π-acceptors. Pleasingly, when substrates con-
taining electron-rich or -deficient aryl groups on the ynal
moiety were subjected to the non-optimized reaction con-
ditions, the corresponding β-Cl/Br-α,β-unsaturated aldehydes
(β-halo-enals) were obtained in moderate to good yields and
with high stereoselectivity (Fig. 2, section IV, compounds 5a,
5b, 5c and 5d).
With the purpose of decreasing the reaction time, we then
evaluated the chlorination protocol under microwave
irradiation. Using the optimized reaction conditions and the
assistance of microwave irradiation, the ynone 1d was success-
fully converted into the corresponding product in both high
yield and stereoselectivity (Fig. 3, 91% yield and 91 : 9 Z/E)
after 30 min.
Scheme 2 Plausible reaction mechanism for the hydrohalogenation
with the in situ generation of H+[XBF3]−.
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extraction – in 92% yield and a 91 : 9 diastereomeric ratio 2H), 7.63–7.56 (m, 1H), 7.52–7.46 (m, 2H), 7.46–7.43 (m, 3H),
(Fig. 3, section b) without further purification as shown in 7.35 (s, 1H). 13C NMR (101 MHz, CDCl3) δ 189.9, 143.3, 137.8,
Fig. 4.
137.4, 133.3, 130.6, 128.8, 128.7, 127.2, 121.5.
On the basis of the experimental results and literature
(Z)-3-Chloro-1-(4-methoxyphenyl)-3-phenylprop-2-en-1-one (2e).
reports,13 we attempted to propose a plausible reaction The title compound was isolated in 96% (39 mg) yield as a
pathway (Scheme 2). First, H+[XBF3]− is in situ generated from yellow solid. H NMR (400 MHz, CDCl3) δ 8.02–7.96 (m, 2H),
1
TMSX and HBF4·OEt2. The H+[XBF3]− behaves as a Brønsted 7.77–7.71 (m, 2H), 7.46–7.40 (m, 3H), 7.27 (s, 1H), 6.99–6.93
acid by activating the carbonyl group – therefore, the nucleophi- (m, 2H), 3.87 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 188.8,
lic transfer of the halide to the ynone generates an allenyl inter- 163.9, 141.9, 137.4, 131.2, 130.4, 128.7, 127.1, 122.1, 114.0,
mediate. Finally, the allenyl intermediate undergoes protona- 55.5.
tion producing the desired β-halo carbonyl compounds.
(Z)-1-(4-Butoxyphenyl)-3-chloro-3-phenylprop-2-en-1-one (2f).
The title compound was isolated in 92% (43 mg) yield as a
yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 8.9 Hz, 2H),
7.74 (dd, J = 6.7, 3.0 Hz, 2H), 7.46–7.39 (m, 3H), 7.27 (s, 1H),
6.94 (d, J = 8.9 Hz, 2H), 4.03 (t, J = 6.5 Hz, 2H), 1.84–1.73 (m,
Conclusions
In summary, we outline an unprecedented and highly efficient 2H), 1.51 (dt, J = 14.9, 7.4 Hz, 2H), 0.98 (t, J = 7.4 Hz, 3H).
protocol for the synthesis of β-halovinyl ketones (Cl, Br and I) 13C NMR (101 MHz, CDCl3) δ 188.8, 163.5, 141.7, 137.4, 131.1,
which are privileged starting materials for the syntheses of 130.3, 128.6, 128.1, 127.1, 122.1, 114.4, 68.0, 31.1, 19.2, 13.8.
heterocyclic compounds. Our method exhibits good functional
(Z)-1-(4-(tert-Butyl)phenyl)-3-chloro-3-phenylprop-2-en-1-one
group compatibility and a broad substrate scope. Also, the (2g). The title compound was isolated in 87% (39 mg) yield as
1
present methodology is operationally simple as it does not a yellow oil. H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 8.7 Hz,
require an inert atmosphere or elevated temperature and pure 2H), 7.77–7.73 (m, 2H), 7.50 (d, J = 8.7 Hz, 2H), 7.42 (d, J =
products can be obtained after an extractive work-up. The 3.5 Hz, 3H), 7.33 (s, 1H), 1.35 (s, 9H). 13C NMR (101 MHz,
exploration of new synthetic strategies involving a similar CDCl3) δ 189.5, 157.2, 142.6, 137.4, 135.1, 130.4, 128.7, 128.7,
reagent combination is underway in our group.
127.2, 125.7, 121.8, 35.2, 31.1.
(Z)-3-Chloro-1-(4-ethylphenyl)-3-phenylprop-2-en-1-one (2h).
The title compound was isolated in 80% (32 mg) yield as a
yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.17–8.12 (m, 2H),
7.71–7.65 (m, 2H), 7.50–7.45 (m, 1H), 7.44–7.39 (m, 2H), 7.34
(d, J = 8.5 Hz, 2H), 2.74 (q, J = 7.6 Hz, 2H), 1.28 (t, J = 7.6 Hz,
Experimental
Hydrochlorination of ynones
To a solution of ynone (0.15 mmol) in 2-MeTHF (0.4 mL) were 3H). 13C NMR (101 MHz, CDCl3) δ 189.6, 150.5, 142.6, 137.4,
added HBF4·OEt2 (82.4 μL, 0.30 mmol, 50 wt/wt%, 2 equiv.) 135.4, 130.4, 129.0, 128.7, 128.3, 127.2, 121.9, 29.0, 15.2.
and TMSCl (1.6 equiv., indicated by superscript a below, or
(Z)-3-Chloro-1-(3-(chloromethyl)phenyl)-3-phenylprop-2-en-
2 equiv.) at room temperature, and then the mixture was 1-one (2i). The title compound was isolated in 85% (37 mg)
monitored by TLC or GC-MS. After completion, the solvent was yield as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.00 (td,
evaporated under reduced pressure and the residue was puri- J = 1.8, 0.5 Hz, 1H), 7.96–7.92 (m, 1H), 7.78–7.74 (m, 2H),
fied by silica gel column chromatography (n-hexanes/EtOAc) to 7.64–7.60 (m, 1H), 7.49 (dd, J = 6.8, 2.9 Hz, 1H), 7.48–7.43 (m,
afford the corresponding products 2a–x.
3H), 7.33 (s, 1H), 4.63 (s, 2H). 13C NMR (101 MHz, CDCl3)
(Z)-4-Chloro-4-phenylbut-3-en-2-one (2a)a. The title com- δ 189.2, 143.9, 138.3, 137.2, 133.3, 130.7, 129.2, 128.7, 128.7,
pound was isolated in 90% (24 mg) yield as a yellow oil. 128.6, 127.2, 121.2, 45.5.
1H NMR (400 MHz, CDCl3) δ 7.70–7.66 (m, 2H), 7.46–7.39 (m,
(Z)-3-Chloro-1-(4-chlorophenyl)-3-phenylprop-2-en-1-one (2j).
3H), 6.78 (s, 1H), 2.48 (s, 3H). 13C NMR (101 MHz, CDCl3) The title compound was isolated in 83% (34 mg) yield as a
1
δ 196.7, 143.0, 137.3, 130.7, 128.7, 127.3, 124.8, 31.9.
yellow solid. H NMR (400 MHz, CDCl3) δ 7.97–7.90 (m, 2H),
(Z)-4-(4-Bromophenyl)-4-chlorobut-3-en-2-one (2b)a. The title 7.79–7.71 (m, 2H), 7.49–7.42 (m, 5H), 7.29 (s, 1H). 13C NMR
compound was isolated in 82% (32 mg) yield as a brown solid. (101 MHz, CDCl3) δ 188.7, 143.9, 139.8, 137.2, 136.1, 130.7,
1H NMR (400 MHz, CDCl3) δ 7.47 (s, 4H), 6.68 (s, 1H), 2.40 (s, 130.1, 129.1, 128.8, 127.2, 121.0.
3H). 13C NMR (101 MHz, CDCl3) δ 196.4, 141.7, 136.2, 131.9,
(Z)-3-Chloro-1-(2-chlorophenyl)-3-phenylprop-2-en-1-one (2k).
128.8, 125.2, 125.0, 31.8.
The title compound was isolated in 99% (41 mg) yield as a
(Z)-4-Chloro-4-(4-(trifluoromethoxy)phenyl)but-3-en-2-one (2c)a. yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.74 (dd, J = 8.0,
The title compound was isolated in 66% (26 mg) yield as a red 1.7 Hz, 2H), 7.59 (ddd, J = 7.5, 1.5, 0.8 Hz, 1H), 7.46–7.34 (m,
1
oil. H NMR (400 MHz, CDCl3) δ 7.75–7.69 (m, 2H), 7.29–7.23 6H), 7.23 (s, 1H). 13C NMR (101 MHz, CDCl3) δ 190.5, 144.6,
(m, 2H), 6.76 (s, 1H), 2.48 (s, 3H). 13C NMR (101 MHz, CDCl3) 139.6, 137.3, 132.1, 130.9, 130.3, 130.0, 128.8, 128.7, 127.4,
δ 196.3, 150.8, 141.2, 135.8, 129.0, 125.3, 120.8, 31.8.
127.2, 123.5.
(Z)-3-Chloro-1.3-diphenylprop-2-en-1-one (2d). The title com-
(Z)-3-Chloro-3-phenyl-1-(4-(trifluoromethyl)phenyl)prop-2-en-
pound was isolated in 95% (34 mg) yield as a yellow oil. 1-one (2l). The title compound was isolated in 79% (42 mg)
1H NMR (400 MHz, CDCl3) δ 8.03–7.97 (m, 2H), 7.79–7.73 (m, yield as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.01 (d,
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J = 8.1 Hz, 2H), 7.68 (t, J = 8.0 Hz, 4H), 7.44–7.33 (m, 3H), 7.27 7.33 (s, 1H), 6.95 (d, J = 8.9 Hz, 2H), 3.86 (s, 3H). 13C NMR
(s, 1H). 13C NMR (101 MHz, CDCl3) δ 188.7, 145.1, 140.6, (101 MHz, CDCl3) δ 189.8, 161.8, 143.9, 138.3, 133.2, 130.8,
137.1, 133.2, 131.0, 129.8, 128.9, 127.3, 125.8 (q, J = 3.5 Hz, 129.0, 128.8, 128.7, 127.1, 114.1, 55.6.
1C), 120.6.
(Z)-3-Chloro-3-cyclohexyl-1-phenylprop-2-en-1-one (2t). The
(Z)-3-Chloro-1-(4-fluoro-2-(trifluoromethyl)phenyl)-3-phenyl- title compound was isolated in 46% (17 mg) yield as an orange
1
prop-2-en-1-one (2m). The title compound was isolated in 80% oil. H NMR (400 MHz, CDCl3) δ 7.94–7.90 (m, 2H), 7.50–7.43
1
(39 mg) yield as a yellow oil. H NMR (400 MHz, CDCl3) δ 7.72 (m, 3H), 7.02 (s, 1H), 3.73 (tt, J = 11.4, 3.3 Hz, 1H), 1.83–1.70
(dd, J = 8.2, 1.5 Hz, 2H), 7.59 (dd, J = 8.5, 5.3 Hz, 1H), (m, 5H), 1.57 (dd, J = 11.7, 3.5 Hz, 2H), 1.44–1.34 (m, 2H),
7.51–7.39 (m, 4H), 7.33 (td, J = 8.1, 3.4 Hz, 1H), 7.08 (s, 1H). 1.27–1.17 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 188.7, 138.2,
13C NMR (101 MHz, CDCl3) δ 190.5, 164.3, 161.8, 146.5, 136.8, 133.0, 128.6, 128.3, 122.4, 42.6, 30.6, 25.6, 21.6.
131.3, 130.8 (d, J = 8.5 Hz, 1C), 128.8, 128.1, 127.4, 123.0, 118.9
(d, J = 21.2 Hz, 1C), 114.7 (dq, J = 25.7 e 5.1 Hz, 1C).
(Z)-3-Chloro-1-phenylhept-2-en-1-one (2u). The title com-
pound was isolated in 65% (22 mg) yield as an orange oil.
(Z)-3-Chloro-1-(3-fluorophenyl)-3-phenylprop-2-en-1-one (2n). 1H NMR (400 MHz, CDCl3) δ 7.95–7.89 (m, 2H), 7.59–7.53 (m,
The title compound was isolated in 87% (34 mg) yield as a 1H), 7.50–7.44 (m, 2H), 7.12 (s, 1H), 3.03–2.92 (m, 2H),
yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.79–7.74 (m, 3H), 1.76–1.60 (m, 2H), 1.49–1.33 (m, 2H), 0.94 (t, J = 7.3 Hz, 3H).
7.70–7.65 (m, 1H), 7.50–7.42 (m, 4H), 7.31 (s, 1H), 7.31–7.25 13C NMR (101 MHz, CDCl3) δ 188.6, 157.8, 138.2, 133.0, 128.7,
(m, 1H). 13C NMR (101 MHz, CDCl3) δ 188.4, 163.0 (d, J = 248.4 128.3, 123.3, 36.2, 29.9, 22.1, 13.8.
Hz, 1C), 144.4, 140.0 (d, J = 6.1 Hz, 1C), 137.2, 130.8, 130.4 (d,
J = 7.7 Hz, 1C), 128.8, 127.2, 124.3 (d, J = 2.4 Hz, 1C), 120.8, 1-one (2v). The title compound was isolated in 98% (40 mg)
120.3 (d, J = 21.5 Hz, 1C), 115.3 (d, J = 22.4 Hz, 1C).
yield as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.97–7.90 (m,
(Z)-3-Chloro-1-(4-methoxyphenyl)-3-(trimethylsilyl)prop-2-en-
(Z)-3-Chloro-1-(3-nitrophenyl)-3-phenylprop-2-en-1-one (2o). 2H), 7.73 (s, 1H), 6.98–6.91 (m, 2H), 3.88 (s, 3H), 0.30–0.28 (m,
The title compound was isolated in 81% (35 mg) yield as a 9H). 13C NMR (101 MHz, CDCl3) δ 188.6, 164.7, 160.3, 138.5,
1
yellow solid. H NMR (400 MHz, CDCl3) δ 8.78 (t, J = 2.0 Hz, 131.8, 131.2, 114.8, 56.4, 0.0.
1H), 8.43 (ddd, J = 8.2, 2.3, 1.1 Hz, 1H), 8.35–8.30 (m, 1H),
(Z)-4-Chlorooct-4-en-2-one (2w′). The title compound was
7.81–7.76 (m, 2H), 7.71 (dd, J = 9.6, 6.3 Hz, 1H), 7.52–7.44 (m, isolated in 50% (12 mg) yield as a yellow oil. 1H NMR
3H), 7.37 (s, 1H). 13C NMR (101 MHz, CDCl3) δ 187.3, 148.5, (400 MHz, CDCl3) δ 5.65 (t, J = 7.0 Hz, 1H), 3.40–3.35 (m, 2H),
146.1, 139.3, 136.9, 134.1, 131.2, 130.0, 128.8, 127.4, 127.3, 2.26–2.16 (m, 5H), 1.51–1.39 (sext, J = 7.4 Hz, 2H), 0.94 (t, J =
123.3, 119.9. M.p. 68–70 °C.
(Z)-3-Chloro-1-(4-methyl-3-nitrophenyl)-3-phenylprop-2-en-1- 53.9, 30.8, 29.0, 21.7, 13.7.
7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ. 204.6, 130.9, 126.8,
one (2p). The title compound was isolated in 87% (40 mg)
(1Z·4E)-1-Chloro-1.5-diphenylpenta-1.4-dien-3-one (2x). The
yield as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.53 (d, J = title compound was isolated in 89% (36 mg) yield as an orange
1.8 Hz, 1H), 8.12 (dd, J = 8.0, 1.8 Hz, 1H), 7.80–7.74 (m, 1H), oil. 1H NMR (400 MHz, CDCl3) δ 7.77–7.72 (m, 2H), 7.68 (d, J =
7.53–7.43 (m, 4H), 7.34 (s, 1H), 2.68 (s, 3H). 13C NMR 16.0, 1H), 7.62–7.56 (m, 2H), 7.50–7.36 (m, 6H), 7.04–7.02 (m,
(101 MHz, CDCl3) δ 187.1, 149.4, 145.5, 138.8, 136.9, 136.9, 2H). 13C NMR (101 MHz, CDCl3) δ.188.6, 144.1, 143.0, 137.40,
133.5, 132.4, 131.0, 128.8, 127.3, 124.8, 120.0, 20.7. M.p. 134.57, 130.72, 130.62, 129.01, 128.7, 128.5, 127.27, 127.1,
117–119 °C.
123.6.
(Z)-3-Chloro-1-(3.4-difluorophenyl)-3-phenylprop-2-en-1-one
(2q). The title compound was isolated in 90% (38 mg) yield as
Hydrobromination of ynones
a yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.84 (ddd, J = 10.6, To a solution of ynone (0.15 mmol) in 2-MeTHF (0.4 mL) were
7.6, 2.1 Hz, 1H), 7.80–7.73 (m, 3H), 7.52–7.41 (m, 3H), added HBF4·OEt2 (82.4 μL, 0.30 mmol, 50 wt/wt%, 2 equiv.)
7.32–7.23 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 187.3, 153.8 and TMSBr (0.3 mmol, 2 equiv.) at room temperature, and
(dd, J = 257.6, 12.9 Hz, 1C), 150.5 (dd, J = 251.5, 12.9 Hz, 1C), then the mixture was monitored by TLC. After completion, the
144.6, 137.0, 134.8 (t, J = 3.6 Hz, 1C), 130.9, 128.8, 127.2, 125.7 solvent was evaporated under reduced pressure and the
(dd, J = 7.1, 3.3 Hz, 1C), 120.4, 117.9 (d, J = 18.3 Hz, 1C), 117.7 residue was purified by silica gel column chromatography
(d, J = 18.0 Hz, 1C). M.p. 37–40 °C.
(n-hexanes/EtOAc) to afford the corresponding products 3a–i.
(Z)-3-Bromo-1.3-diphenylprop-2-en-1-one (3a). The title com-
(Z)-3-Chloro-3-(4-nitrophenyl)-1-phenylprop-2-en-1-one (2r).
The title compound was isolated in 99% (43 mg) yield as a pound was isolated in 80% (34 mg) yield as a yellow oil. 1H
1
yellow solid. H NMR (400 MHz, CDCl3) δ 8.29 (d, J = 8.9 Hz, NMR (400 MHz, CDCl3) δ 8.02 (d, J = 8.5 Hz, 2H), 7.74–7.68 (m,
2H), 8.00 (d, J = 7.3 Hz, 2H), 7.92 (d, J = 8.9 Hz, 2H), 7.64–7.61 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.52 (s, 1H), 7.43 (t, J = 8.9 Hz,
(m, 1H), 7.51 (t, J = 7.7 Hz, 2H), 7.42 (s, 1H). 13C NMR 3H), 7.46–7.40 (m, 3H). 13C NMR (101 MHz, CDCl3) δ 190.5,
(101 MHz, CDCl3) δ 189.7, 148.8, 143.1, 139.8, 137.0, 134.0, 139.2, 137.2, 134.2, 133.5, 130.4, 128.8, 128.8, 128.6, 128.0,
129.0, 128.9, 128.2, 125.0, 124.0.
(Z)-3-Chloro-3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one (2s).
125.62.
(Z)-3-Bromo-3-phenyl-1-(4-(trifluoromethyl)phenyl)prop-2-en-
The title compound was isolated in 75% (31 mg) yield as a 1-one (3b). The title compound was isolated in 83% (44 mg)
1
yellow solid. H NMR (400 MHz, CDCl3) δ 8.01–7.97 (m, 2H), yield as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.11 (d, J =
7.73 (d, J = 8.9 Hz, 2H), 7.60–7.56 (m, 1H), 7.51–7.46 (m, 2H), 8.1 Hz, 2H), 7.76 (d, J = 8.2 Hz, 2H), 7.73–7.70 (m, 2H), 7.52 (s,
524 | Org. Biomol. Chem., 2019, 17, 519–526
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1H), 7.45 (dd, J = 5.1, 1.9 Hz, 3H). 13C NMR (101 MHz, CDCl3) residue was purified by silica gel column chromatography
δ 189.3, 140.1, 139.0, 136.1, 130.7, 130.2, 129.1, 128.7, 128.2, (n-hexanes/EtOAc) to afford the corresponding products 4a–e.
128.1, 125.8, 124.6. M.p. 77–80 °C.
(Z)-3-Iodo-1.3-diphenylprop-2-en-1-one (4a). The title com-
(Z)-3-Bromo-1-(4-methyl-3-nitrophenyl)-3-phenylprop-2-en-1- pound was isolated in 89% (45 mg) yield as a yellow oil. 1H
one (3c). The title compound was isolated in 80% (42 mg) NMR (400 MHz, CDCl3) δ 8.01 (d, J = 7.1 Hz, 2H), 7.65–7.56 (m,
yield as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 3H), 7.54 (s, 1H), 7.49 (t, J = 7.8 Hz, 2H), 7.39 (m, 3H). 13C
1.9 Hz, 1H), 8.14 (dd, J = 8.0, 1.8 Hz, 1H), 7.75–7.69 (m, 2H), NMR (101 MHz, CDCl3) δ 190.5, 143.2, 138.7, 137.0, 133.5,
7.52–7.41 (m, 5H), 2.69 (s, 3H). 13C NMR (101 MHz, CDCl3) 131.6, 130.0, 128.8, 128.7, 128.5, 113.3.
δ 187.8, 149.4, 138.9, 138.8, 136.6, 136.4, 133.5, 132.5, 130.8,
128.7, 128.1, 124.9, 124.1, 20.7. M.p. 103–107 °C.
(Z)-3-Iodo-3-phenyl-1-(4-(trifluoromethyl)phenyl)prop-2-en-1-
one (4b). The title compound was isolated in 96% (58 mg)
1
(Z)-3-Bromo-1-(4-(tert-butyl)phenyl)-3-phenylprop-2-en-1-one yield as a yellow oil. H NMR (400 MHz, CDCl3) δ 8.11 (d, J =
(3d). The title compound was isolated in 80% (41 mg) yield as 8.1 Hz, 2H), 7.76 (d, J = 8.2 Hz, 2H), 7.66–7.59 (m, 3H), 7.57 (s,
1
a yellow oil. H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.4 Hz, 1H), 7.46–7.38 (m, 4H). 13C NMR (101 MHz, CDCl3) δ 189.2,
2H), 7.62 (dd, J = 6.5, 3.0 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 143.1, 139.9, 138.0, 130.4, 129.1, 128.9, 128.8, 128.6, 128.2,
7.42 (s, 1H), 7.37–7.30 (m, 3H), 1.25 (s, 9H). 13C NMR 125.8, 115.5.
(101 MHz, CDCl3) δ 190.2, 157.4, 139.3, 134.6, 133.6, 130.2,
(Z)-1-(4-Butoxyphenyl)-3-iodo-3-phenylprop-2-en-1-one (4c).
128.8, 128.8, 128.6, 128.0, 125.8, 35.2, 31.1.
The title compound was isolated in 93% (56 mg) yield as a
(Z)-3-Bromo-3-(4-nitrophenyl)-1-phenylprop-2-en-1-one (3e). brown oil. 1H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 9.0 Hz, 2H),
The title compound was isolated in 97% (48 mg) yield as a 7.63–7.58 (m, 2H), 7.46 (s, 1H), 7.42–7.35 (m, 3H), 6.95 (d, J =
1
yellow solid. H NMR (400 MHz, CDCl3) δ 8.28 (d, J = 9.0 Hz, 9.0 Hz, 2H), 4.04 (t, J = 6.5 Hz, 2H), 1.84–1.73 (m, 2H),
2H), 8.01 (dd, J = 8.4, 1.3 Hz, 2H), 7.91–7.84 (m, 3H), 7.60, 1.56–1.44 (m, 2H), 0.98 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz,
7.57–7.49 (m, 3H). 13C NMR (101 MHz, CDCl3) δ 190.2, 144.8, CDCl3) δ 189.6, 163.6, 143.2, 139.0, 132.3, 131.2, 129.8, 128.7,
136.4, 134.0, 131.3, 130.2, 129.6, 128.9, 128.8, 123.8, 123.4.
128.5, 114.4, 111.6, 68.0, 31.1, 19.2, 13.8.
(Z)-3-Bromo-3-(4-methoxyphenyl)-1-(p-tolyl)prop-2-en-1-one
(Z)-3-Iodo-3-(4-nitrophenyl)-1-phenylprop-2-en-1-one
(4d).
(3f). The title compound was isolated in 98% (48 mg) yield as The title compound was isolated in 94% (53 mg) yield as a
a yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.00 (dd, J = 8.4, yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.27 (d, J = 9.0 Hz, 2H),
1.3 Hz, 1H), 7.68 (d, J = 9.1 Hz, 1H), 7.61–7.55 (m, 1H), 8.01 (dd, J = 8.4, 1.3 Hz, 2H), 7.77 (d, J = 9.0 Hz, 2H), 7.64 (t,
7.52–7.48 (s, 3H), 6.93 (d, J = 9.0 Hz, 1H), 3.85 (s, 2H). 13C J = 7.4 Hz, 1H), 7.60 (s, 1H), 7.53 (t, J = 7.6 Hz, 2H). 13C NMR
NMR (101 MHz, CDCl3) δ 190.2, 161.4, 137.7, 134.8, 133.3, (101 MHz, CDCl3) δ 190.4, 149.0, 139.8, 134.5, 134.0, 129.6,
131.5, 130.8, 129.7, 128.7, 123.4, 113.9, 55.5.
129.0, 128.8, 123.7, 123.4, 108.5.
(Z)-4-Bromo-4-phenylbut-3-en-2-one (3g). The title com-
(Z)-3-Iodo-3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one (4e).
pound was isolated in 82% (28 mg) yield as a yellow oil. The title compound was isolated in 86% (47 mg) yield as a
1H NMR (400 MHz, CDCl3) δ 7.42–7.19 (m, 5H), 6.92 (s, 1H), brown oil. 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 8.5 Hz, 2H),
2.37 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 196.7, 139.4, 133.7, 7.60 (d, J = 9.0 Hz, 2H), 7.51 (s, 1H), 7.52–7.45 (m, 3H), 6.90 (d,
130.4, 128.6, 128.2, 128.0, 31.8.
J = 8.9 Hz, 2H), 3.85 (s, 3H). 13C NMR (101 MHz, CDCl3)
(Z)-3-Bromo-1-phenylhept-2-en-1-one (3h). The title com- δ 190.2, 161.2, 133.3, 130.5, 129.4, 128.7, 128.6, 127.0, 113.8,
pound was isolated in 80% (32 mg) yield as a yellow oil. 113.3, 92.4, 55.4.
1H NMR (400 MHz, CDCl3) δ 7.92–7.87 (m, 2H), 7.40 (t, J =
7.6 Hz, 3H), 5.76 (t, J = 6.9 Hz, 1H), 4.05 (s, 2H), 2.12 (q, J =
Hydrohalogenation of ynals
7.1 Hz, 2H), 1.37 (m, 2H), 0.85 (t, J = 7.4 Hz, 3H). 13C NMR To a solution of ynal (0.15 mmol) in 2-MeTHF (0.4 mL) were
(101 MHz, CDCl3) δ 195.6, 136.4, 133.9, 133.4, 128.7, 128.4, added HBF4·OEt2 (82.4 μL, 0.30 mmol, 50 wt/wt%, 2 equiv.)
118.5, 50.5, 33.6, 21.6, 13.7.
and TMSX (X = Cl or Br, 0.30 mmol, 2 equiv.) at room tempera-
(Z)-3-Bromo-1-(4-methoxyphenyl)-3-(trimethylsilyl)prop-2-en- ture, and then the mixture was monitored by TLC. After com-
1-one (3i). The title compound was isolated in 89% (42 mg) pletion, the solvent was evaporated under reduced pressure
yield as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.78 (d, J = and the residue was purified by silica gel column chromato-
9.0 Hz, 2H), 7.19 (s, 1H), 6.81 (d, J = 9.0 Hz, 2H), 3.73 (s, 3H), graphy (n-hexanes/EtOAc) to afford the corresponding products
0.15 (s, 9H). 13C NMR (101 MHz, CDCl3) δ 193.4, 166.1, 140.3, 5a–d.
139.2, 133.7, 131.0, 116.1, 57.6, 0.0. M.p. 69–73 °C.
(Z)-3-Chloro-3-(4-nitrophenyl)acrylaldehyde (5a). The title
compound was isolated in 46% (14 mg) yield as a red solid.
1H NMR (400 MHz, CDCl3) δ 10.25 (d, J = 6.6, 1H), 8.32 (d, J =
8.9, 2H), 7.93 (d, J = 8.9, 2H), 6.75 (d, J = 6.7, 1H). 13C NMR
Hydroiodination of ynones
To a solution of ynone (0.15 mmol) in 2-MeTHF (0.4 mL) were (101 MHz, CDCl3) δ 190.6, 141.4, 133.9, 130.6, 128.2, 126.8,
added HBF4·OEt2 (82.4 μL, 0.30 mmol, 50 wt/wt%, 2 equiv.) 124.1. M.p. 121–123 °C.
and TMSI (0.3 mmol, 2 equiv.) at – 20 °C in the dark, and then
(Z)-3-Bromo-3-(4-nitrophenyl)acrylaldehyde (5b). The title
the mixture was monitored by TLC. After completion, the compound was isolated in 81% (31 mg) yield as a red solid.
solvent was evaporated under reduced pressure and the 1H NMR (400 MHz, CDCl3) δ 10.08 (d, J = 6.3 Hz, 1H), 8.31 (d,
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J = 9.0 Hz, 2H), 7.88 (d, J = 9.0 Hz, 2H), 6.87 (d, J = 6.4 Hz, 1H).
13C NMR (101 MHz, CDCl3) δ 192.8, 149.3, 143.3, 141.1, 129.8,
129.0, 124.0.
J. Heterocycl. Chem., 2005, 42, 1253; (f) A. E. Pohland and
W. R. Benson, Chem. Rev., 1966, 66, 161.
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R. I. Ibragimov, Chem. Heterocycl. Compd., 2005, 41, 1009;
(b) H. Y. Kim, J.-Y. Li and K. Oh, J. Org. Chem., 2012, 24,
11132; (c) V. A. Kobelevskaya, L. I. Larina, A. V. Popov,
E. V. Rudyakova and G. G. Levkovskaya, Russ. J. Org. Chem.,
2015, 51, 231; (d) H. Y. Kim, E. Song and K. Oh, Org. Lett.,
2017, 19, 312; (e) H. Y. Kim and K. Oh, Org. Lett., 2015, 17,
6254; (f) H. Y. Kim, S. Lee, S. Kim and K. Oh, Org. Lett.,
2015, 3, 450; (g) H. Y. Kim and K. Oh, Org. Lett., 2014, 22,
5934.
(Z)-3-Bromo-3-(4-bromophenyl)acrylaldehyde (5c). The title
compound was isolated in 83% (36 mg) yield as a yellow solid.
1H NMR (400 MHz, CDCl3) δ 10.05 (d, J = 6.5 Hz, 1H),
7.60–7.55 (m, 4H), 6.77 (d, J = 6.5 Hz, 1H). 13C NMR (101 MHz,
CDCl3) δ 193.5, 143.5, 136.5, 132.2, 129.6, 127.8, 126.5.
(Z)-3-Bromohept-2-en-1-ol (5d). The title compound was iso-
1
lated in 36% (8 mg) yield as a yellow oil. H NMR (400 MHz,
CDCl3) δ 5.93 (tt, J = 6.0, 1.1 Hz, 1H), 4.26 (d, J = 6.1 Hz, 2H),
2.46 (td, J = 7.8, 0.9 Hz, 2H), 1.55 (m, 3H), 1.33 (sext, J = 7.3 Hz,
2H), 0.92 (t, J = 7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3)
δ 130.9, 127.4, 62.4, 41.2, 30.1, 21.6, 13.8.
3 H. Y. Kim, E. O. Rooney, R. P. Meury and K. Oh, Angew.
Chem., Int. Ed., 2013, 52, 8026.
4 H. Y. Kim, J.-Y. Li and K. Oh, Angew. Chem., Int. Ed., 2013,
52, 3736.
Procedure for the synthesis of compound 2d (Fig. 3b)
5 T. Iwai, T. Fujihara, J. Terao and Y. Tsuji, J. Am. Chem. Soc.,
2009, 131, 6668.
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2008, 10, 5469.
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2012, 134, 1268.
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2010, 46, 5891; (b) P. Gandeepan, K. Parthasarathy, T.-H. Su
and C.-H. Cheng, Adv. Synth. Catal., 2012, 354, 457.
9 (a) K. Oh, H. Kim, F. Cardelli, T. Bwititi and
A. M. Martynow, J. Org. Chem., 2008, 73, 2432;
(b) H. Y. Kim, J.-Y. Li and K. Oh, J. Org. Chem., 2012, 77,
11132; (c) J. Zhang, L. Liu, J. Duan, L. Gu, B. Chen, T. Sun
and Y. Gong, Adv. Synth. Catal., 2017, 359, 4348;
(d) H. Zhou, C. Zeng, L. Ren, W. Liao and X. Huang,
Synlett, 2006, 3504.
To a solution of 1,3-diphenylprop-2-yn-1-one 1d (1.03 mg,
5 mmol) in 2-MeTHF (13 mL) were added HBF4·OEt2 (2.75 mL,
10 mmol, 50 wt/wt%, 2 equiv.) and TMSCl (10 mmol, 1.25 mL,
2 equiv.) at room temperature, and then the mixture was moni-
tored by TLC or GC-MS. After the completion of the reaction,
water (50 mL) was added to the reaction. This mixture was
extracted with ethyl acetate (3 × 30 mL). The organic layers
were combined, dried over anhydrous sodium sulfate (Na2SO4)
and the solvent was evaporated under reduced pressure to give
product 2d in 92% (1.12 g) yield without further purification.
Conflicts of interest
There are no conflicts to declare.
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Acknowledgements
V. A. F. da Silva and B. T. Matsuo acknowledge FAPESP (2016/
14560-6) and CNPq for their master and Ph.D fellowships,
respectively. M. W. Paixão gratefully acknowledges financial
support from INCT Catálise, CNPq and FAPESP (14/50249-8,
15/17141-1 and 16/12622-4). The authors acknowledge GSK, as
well, for the financial support. R. L. Davis gratefully acknowl-
edges financial support from the NSERC and G. P. da Silva
acknowledges the Emerging Leaders in the Americas Program
for support. A. Ali acknowledges TWAS-CNPq and Higher
Education Commission (HEC) of Pakistan for their support.
11 X. Zeng, Z. Lu, S. Liu, G. B. Hammond and B. Xu, J. Org.
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526 | Org. Biomol. Chem., 2019, 17, 519–526
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