Silver hexafluoroantimonate-catalyzed direct α-alkylation of unactivated ketones

Article abstract of DOI:10.1002/adsc.201400870

A practically simple and direct α-alkylation of unactivated ketones using benzylic alcohols has been achieved. The in situ formed acetals are the key for the success of the reaction. The catalyst, silver hexafluoroantimonate(V) (AgSbF₆) provide

Full text of DOI:10.1002/adsc.201400870

FULL PAPERS
DOI: 10.1002/adsc.201400870
Silver Hexafluoroantimonate-Catalyzed Direct a-Alkylation of
Unactivated Ketones
Naganaboina Naveen,a Srinivasa Rao Koppolu,a and Rengarajan Balamurugana,*
a
School of Chemistry, University of Hyderabad, Hyderabad – 500046, India
Fax : (+91)-40-2301-2460; phone: (+91)-40-2313-4817; e-mail: rbsc@uohyd.ernet.in
Received: September 3, 2014; Revised: January 16, 2015; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201400870.
Abstract: A practically simple and direct a-alkyla- center at the benzylic position of the benzylic alco-
tion of unactivated ketones using benzylic alcohols hol. The alcohols include benzylic propargyl alcohols,
has been achieved. The in situ formed acetals are the cinnamyl alcohols, and diarylmethanols.
key for the success of the reaction. The catalyst,
silver hexafluoroantimonate(V) (AgSbF6) provides
double activation by converting the ketone into an Keywords: a-alkylations; cinnamyl alcohols; diary-
enol ether via acetal and generation of carbocationic lmethanols; ketones; propargylic alcohols; silver
Introduction
a proper match between the electrophilicity (E) of
the cation and the nucleophilicity (N) of the anion
The direct a-alkylation of ketones is a challenging which are strongly influenced by the nature of the
task due to the low acidity of the a-hydrogens. The substituents.[5] This can easily be understood from the
pKa value of the a-hydrogen of simple unactivated limited substrate scope of diarylmethanols in the alky-
ketones is in the range of 18–20 in water (24–27 in lation reactions with ketones.[3e,4e] In our research en-
DMSO)[1] which indicates that it is less acidic and re- deavours to utilize in situ formed acetals[6] we have
quires stronger reaction conditions for alkylation at found that a stoichiometric amount of TfOH is able
the a position. Classical literature methods involve to promote the direct a-alkylation of different ke-
the use of strong bases like LDA etc. to form reactive tones with a wide range of benzylic alcohols at room
metal enolates or conversion of ketones into more nu- temperature.[6c] The success of the reaction is due to
cleophilic enamines, silyl enol ethers etc.[2] Also, the the formation of methyl vinyl ether from the ketone
electrophiles used have good leaving groups such as via an in situ generated acetal formed by the reaction
triflate, iodide, bromide etc. In these classical meth- of trimethyl orthoformate with the ketone in the pres-
ods, use of a quantitative amount of a strong base and ence of triflic acid.[7] This methyl vinyl ether formed
other reagents is a matter of concern as equivalent in the reaction reacts with the carbocationic electro-
quantities of inorganic metal salts are generated as philes generated from the benzylic alcohol. Although
by-products.
the reaction worked well with diarylmethanols and
In this regard, the direct alkylation of ketones, cinnamyl alcohol derivatives, benzylic propargyl alco-
without prior activation and avoiding incorporation of hols resulted in only moderate yields of the products.
good leaving groups on the electrophile involving ad- The product of a-propargylation of the ketone is
ditional synthetic steps, will have great synthetic po- a simple precursor for the synthesis of substituted
tential and possible application in industrial processes. furan derivatives.[8] Although the direct propargyla-
Recent times have witnessed some inovations along tion of 1,3-diketones is easy to achieve,[9] direct a-
these lines.[3] Direct a-alkylation of ketones employ- propargylation of ketones has been reported on few
ing alcohols as electrophiles has a definite advantage occasions only. Uemura and co-workers disclosed the
as the by-product formed is water.[4,3b–e] Mostly, alco- first straightforward synthesis of g-alkynones using
hols such as benzylic alcohols which can easily gener- a novel thiolate-bridged diruthenium complex and an
ate carbocations have been employed in these studies. excess amount of ketone.[10] Other methods use either
However, such SN1 type alkylations are not as ketones in the form of enol acetates/silyl enol ethers
straightforward as they appear. There has to be or propargyl alcohols in the form of propargyl ace-
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
ÞÞ
These are not the final page numbers!

FULL PAPERS
Naganaboina Naveen et al.
tates.[11] An interesting asymmetric propargylation
using enamines and propargyl acetate has been re-
ported by Hou et al.[11f] The other methods for
making g-alkynones include conjugate addition of
acetylides to enones[12] or three-component coupling
of an aldehyde, a silyl enol ether and an alkynyl
iodide.[13]
Table 1. Optimization of the reaction condition for the a-
propargylation of ketones.[a]
Nucleophilic substitution of propargyl alcohols is
a direct way to introduce different nucleophiles at the
propargylic carbon.[14] The Nicholas reaction stands as
a traditional method for nucleophilic substitution of
propargyl alcohols.[15] Diruthenium and rhenium
metal complexes have also been used efficiently for
the said reaction.[10b,16] Campagne and co-workers
have shown the utility of a gold catalyst for the effec-
tive activation of propargyl alcohol for the nucleophil-
ic substitution of propargyl alcohols with different nu-
cleophiles.[17] Along these lines, Sheppard and co-
workers have found a silver catalyst to activate prop-
argyl alcohols for the nucleophilic substitution with
oxygen, nitrogen and carbon nucleophiles.[18] Inspired
by this, we tried the direct propargylation of unacti-
vated ketones with propargyl alcohols with silver and
other Lewis acid catalysts via in situ formed acetals.
In addition to the activation of propargyl alcohol, the
Lewis acidity of the catalyst is required to form the
Entry
Catalyst
Solvent
Yield [%][b]
3a
4a
1
2
3.
4.
5
6
7
8
9
10
11
12
13
4
anhydrous AlCl3
CuCl
Cu(OTf)2
AgCl
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DCE
nr
nr
nr
nr
nr
nr
0
AgNO3
Au(PPh3)Cl
Yb(OTf)3
InCl3
PtCl4
AuCl3
88
0
0
85[d]
80[d]
44
52
50
37
58
68
59
70
43
Sn(OTf)2
FeCl3
AgOTf (5 mol%)[c]
AgOTf (5 mol%)
AgOTf
15
necessary enol ether from the in situ generated acetal 16
AgBF4
AgSbF6
AgSbF6
AgSbF6
17
18
19
20
21
22
of the unactivated ketone. In this regard we have
found that silver hexafluoroantimonate(V) (AgSbF6)
is an efficient catalyst for the direct alkylation of ke-
tones.
toluene
THF
CH2Cl2
CH2Cl2
70[d]
40[d]
AgSbF6[e]
AgSbF6
nr
46
HSbF6
[a]
In all experiments except the one presented in entry 13,
1:1:2 equiv. of 1a, 2a and HC(OMe)3 were used.
Isolated yields.
1:1:1.2 equiv. of 1a, 2a and HC(OMe)3.
NMR conversion with respect to 2a.
Without HC(OMe)3, nr=no reaction.
Results and Discussion
[b]
[c]
[d]
[e]
The study began with an investigation of the catalytic
a-propargylation of ketones. Taking 1a and 2a as
model substrates, the reaction was screened with dif-
ferent catalysts to find the most appropriate one. The
reaction was first attempted with more oxophilic
AlCl3 but no alkylation reaction occurred (Table 1, 5 mol% AgOTf only 37% of the product 3a was iso-
entry 1). Similarly no product was obtained when the lated (Table 1, entry 13). When HC(OMe)3 was taken
reaction was carried out with catalysts such as CuCl, in 2 equivalents the yield further increased to 58%
Cu(OTf)2, AgCl, AgNO3 and Au(PPh3)Cl. With (Table 1, entry 14). Encouragingly with 10 mol% of
Yb(OTf)3, the corresponding methyl ether of the AgOTf the reaction resulted in a 68% yield of the
propargyl alcohol 4a was formed as the product. It product (Table 1, entry 15). It is important to note
was obtained in 88% isolated yield. InCl3 and PtCl4 that without HC(OMe)3 the reaction failed to give
also showed similar results and the formed methyl the product (Table 1, entry 21). Under the reaction
ether remained as such even after 24 h. A positive conditions, AgBF4 gave 59% yield. AgOTf and
result was observed when AuCl3 was used as the cata- AgSbF6 are equally effective and gave nearly the
lyst and the desired product 3a was obtained in 44% same yields. Among these two, AgSbF6 was slightly
yield. Reactions involving Sn(OTf)2 and FeCl3 cata- better resulting in 70% yield. Since AgSbF6 was
lysts resulted in 52% and 50% yields of 3a, respec- found to be better, further optimizations were done
tively. Silver catalysts with weakly coordinating coun- using it in different solvents. Out of the solvents
ter anions gave better yields than other catalysts. screened, chlorinated solvents were found to be
When a mixture of 1a, 2a and HC(OMe)3 taken in better than other solvents. In CHCl3 and DCE, 54%
1:1:1.2 equivalents, respectively, was treated with and 43% yields were noticed, respectively. In DMF,
2
asc.wiley-vch.de
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

FULL PAPERS
Silver Hexafluoroantimonate-Catalyzed Direct a-Alkylation
Scheme 1. Substrate scope for a-propargylation.
THF and toluene the reactions did not result in the as AgSbF6 and the reaction involving HSbF6 resulted
desired product. However the methyl ether 4a was in 46% of 3a (Table 1, entry 22). In order to probe
obtained in the reactions carried out in toluene and the involvement of in situ formed acetals in this reac-
THF. The Brønsted acid HSbF6 was not as effective tion a couple of reactions were carried out. In the
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3
ÞÞ
These are not the final page numbers!

FULL PAPERS
Naganaboina Naveen et al.
cases we found that two equivalents of ketone were
necessary for obtaining better yields. Simple diphenyl-
propargyl alcohol gave lower yields when compared
to the propargyl alcohol derivative having an elec-
tron-donating methoxy substituent on one of the
phenyl rings (Scheme 1, entries 1 and 4; 2 and 5).
Owing to the importance of the thiophene moiety
in drugs[19] we incorporated thiophene as one of the
substituents in the propargyl alcohol. To our delight
the reaction worked without any problem (Scheme 1,
entries 15–18). With substituents like CF3/fluoro on
one of the phenyl rings of propargyl alcohols the reac-
tion failed to deliver the expected products. With
these propargyl alcohols, the required benzylic carbo-
cation may not form, because of the destabilizing
effect of the electron-withdrawing groups. The possi-
ble allene product was not obtainedI in any of the re-
actions. Terminal and aliphatic propargyl alcohols did
Scheme 2. Alkylation using enantioenriched propargyl alco-
hol.
first reaction, the dimethyl acetal of acetophenone not react under theses reaction conditions to afford
was treated with 2a in the presence of 10 mol% of the corresponding a-alkylated products.
AgSbF6 for 24 h. This reaction resulted in 23% of the
In the AgSbF6-catalyzed a-alkylation reactions
desired product 3a along with 55% of acetophenone using propargyl alcohols, the corresponding methyl
which might form under the reaction condition by de- ether of the propargyl alcohol is formed first which is
protection of the acetal. In another experiment, the consumed during the course of the reaction as the a-
reaction of the dimethyl acetal of acetophenone with alkylated product starts forming. This might be the
2a was carried out in the presence of 1 equivalent of reason for the better yields obtained with 2 equiva-
trimethyl orthoformate and 10 mol% of AgSbF6. Tri- lents of HC(OMe)3 during the optimization studies.
methyl orthoformate was added intentionally to main- To have a better insight into the mechanism of pres-
tain a good concentration of acetal by converting ent a-propargylation reaction (whether SN1 or SN2)
back the acetophenone which is formed during the we did an AgSbF6-catalyzed a-alkylation reaction
course of the reaction by deprotection. This reaction using enantioenriched propargyl alcohol (S)-2a with
improved the yield of 3a to 48%. Still 11% of aceto- acetophenone (Scheme 2). However, this reaction re-
phenone was isolated from this reaction. These two sulted in racemic 3a. Since the reaction takes place
experiments show the involvement of an intermediate via methyl ether formation, the racemization can take
acetal in this alkylation reaction.
place either during the methyl ether formation or in
The conditions presented in entry 17 of Table 1 the alkylation step involving a methyl ether. When
were used to study the substrate scope. Under these (S)-2a was treated with HC(OMe)3 in the presence of
conditions a variety of ketones was reacted with dif- AgSbF6 catalyst, it resulted in racemic methyl ether
ferent diarylpropargyl alcohols and the results are 4a. Hence it is believed that methyl ether formation
presented in Scheme 1.
takes place via a propargylic cation.
The nature of substituents (electron-donating and
Based on the above experiments using enantioen-
electron-withdrawing) on the phenyl ring of acetophe- riched propargyl alcohol (Scheme 2), a plausible
none does not have much influence on the yields of mechanism as shown in Scheme 3 can be visualized to
the products. The highest yield of 88% was achieved explain the direct propargylation. The in situ formed
when methylenedioxyacetophenone was reacted acetal 5 of the ketone eliminates a molecule of
with
1-(4-methoxyphenyl)-3-phenylprop-2-yn-1-ol MeOH to generate methyl vinyl ether 6[20] which will
(Scheme 1, entry 8). A drastic decrease in the yield of be in equilibrium with the acetal. Under the influence
the product was observed in the reaction of ortho-bro- of AgSbF6 the benzylic propargyl alcohol generates
moacetophenone compared that of its para-analogue a carbocation 8 which is quenched by HC(OMe)3 to
(Scheme 1, entries 9 and 10). Interestingly, acetylthio- form the methyl ether 4 and sets up an equilibrium in
phene reacted smoothly to furnish a 60% yield of 3k the presence of AgSbF6. Alkylation of the enol ether
(Scheme 1, entry 11). Propiophenone and butyrophe- 6 with the carbocation generates the intermediate 9
none resulted in diastereomeric mixtures of the prod- which eventually will result in the product 3.
ucts as expected (Scheme 1, entries 12 and 13). Even
We then shifted our focus to the allylation using
aliphatic ketones such as acetone and cyclohexanone cinnamyl alcohols[21] and we were pleased to find that
reacted nicely to furnish the respective monoalkylated the same optimized conditions delivered the desired
products (Scheme 1, entries 14–16 and 19). In these products in moderate yields as shown in Scheme 4.
4
asc.wiley-vch.de
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

FULL PAPERS
Silver Hexafluoroantimonate-Catalyzed Direct a-Alkylation
Scheme 3. Tentative mechanism for the direct propargylation.
Scheme 4. Scope of the silver-catalyzed a-allylation reaction.
These reactions required more time. Also the a-allya- nitro group on the aryl ring was subjected to the reac-
tion reactions using catalytic AgSbF6 resulted in tion conditions (Scheme 4, entry 4), a 41% yield of
lower yields and required more time than that of 11d was isolated. It is worth mentioning that the reac-
TfOH-promoted reactions.[6c] When the acetophenone tion of acetone with cinnamyl alcohol derivative 10m
derivative containing a strong electron-withdrawing resulted in a 56% yield of a-allylated product with
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
5
ÞÞ
These are not the final page numbers!

FULL PAPERS
Naganaboina Naveen et al.
Scheme 5. Substrate scope for a-alkyation using diarylmethanols.
catalytic AgSbF6 (Scheme 4, entry 13), whereas the generally, easy for the nucleophiles to react with
same reaction using TfOH[6c] resulted in only a trace stable carbocations but the problem arises with
amount of the product. Allyl alcohols having aryl weakly stabilized carbocations. The other issue with
rings at both the carbinol carbon and the double bond diarylmethanols is that they undergo self-redox reac-
only underwent alkylation reactions.
tions.[4j] Simple diarylmethanols with electron-rich
Finally, the direct a-alkylation was attempted with groups like methyl, methylenedioxy, methoxy on the
diarylmethanols. Several diarylmethanols with func- aryl ring could be reacted (Scheme 5, entries 3–11, 14
tional groups having different electronic effects and 15). Less stabilized diarylmethyl cations generat-
(having different electrophilicities E according to ed
from
(4-fluorophenyl)(phenyl)methanol
Mayrꢁs reactivity scale)[5] were prepared and subject- (Scheme 5, entry 12) and bis(4-chlorophenyl)metha-
ed to a-alkylation of different ketones. Unlike the re- nol (Scheme 5, entry 13) were reacted with acetophe-
actions of arylpropargyl alcohols and cinnamyl alco- none to furnish 78% and 74% of yields of the respec-
hol derivatives, these reactions required heating. A tive alkylated products without any difficulty.
wide range of substrates could be employed
2-Acetylthiophene could also be employed and its
(Scheme 5). Aryl methyl ketones containing different reaction with benzo[d][1,3]dioxol-5-yl(phenyl)metha-
functional groups like iodo, methyl, methoxy, dichloro nol resulted in the corresponding alkylated product in
on the aryl ring were employed to get moderate to 68% yield. As expected, ketones such as cyclohexa-
good yields of the expected a-alkylated products. It is, none and propiophenone resulted in the correspond-
6
asc.wiley-vch.de
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

FULL PAPERS
Silver Hexafluoroantimonate-Catalyzed Direct a-Alkylation
kylation.[11b] After the formation of g-alkynone 3d
under the conditions presented in Scheme 1, the sol-
vent was removed and toluene and PTSA (1 equiv.)
were added and the mixture was heated at 1108C for
2 h to get the furan derivative 8. This reaction was
better as it resulted in a 42% yield of the product
over two steps (Scheme 6).
Conclusions
A catalytic version for the direct a-alkylation of ke-
tones utilizing the in situ formed acetals has been de-
veloped. Benzylic alcohols such as arylpropargyl alco-
hol, cinnamyl alcohols, and diraylmethanols can be
used. a-Propargylation could be used in an one-pot
protocol to make substituted furan derivatives.
Experimental Section
Scheme 6. One-pot formation of a furan.
General Procedure for AgSbF6-Catalyzed Reactions
ing products as mixtures of diastereomers (Scheme 5, using Benzylic Propargyl and Cinnamyl alcohols
entries 14 and 15). In some instances AgOTf was used
as catalyst in DCE solvent at 808C as AgSbF6 was
Benzylic alcohol (2/10, 1.2 equiv.) was weighed into a clean
and dry round-bottom flask and kept under a nitrogen at-
mosphere. Dichloromethane (3 mL per 0.5 mmol of 1),
ketone (1, 1 equiv.), and trimethyl orthoformate (2 equiv.)
found to be less effective (Scheme 5, entries 3, 4 and
5). As found in the TfOH-promoted reaction,[6c] bis[4-
(dimethylamino)phenyl]methanol which will give
a stable carbocation did not give the corresponding a-
alkylated product with acetophenone under the pres-
ent AgSbF6-catalyzed condition. In the TfOH-pro-
moted reactions, TfOH was required in equivalent
amounts in order to get the products. So a reaction
(between acetophenonone and diphenylmethanol)
was attempted with 10 mol% of stronger Brønsted
acid HSbF6 under reflux for 24 h. This reaction, inter-
estingly, resulted in 3a in 42% yield which is lower
than that of the AgSbF6-catalyzed reaction. When
compared to the TfOH-promoted reactions with di-
were added to it and the mixture was stirred until it become
a homogenous solution. Then AgSbF6 (10 mol%) was added
and the reaction mixture was stirred at room temperature
under a nitrogen atmosphere until the completion of the re-
action. After completion of the reaction, the solvent was
evaporated and the crude product was directly loaded on
a silica gel column. Mixtures of ethyl acetate and hexanes
were used as eluents to get the pure products. The data of
new compounds are reported here and some of the com-
pounds prepared in this work were already reported in the
literature.[6c,12 13]
ACHTUNGTRENNUNG
arylmethanols,[6c] the corresponding AgSbF6-catalyzed
General Procedure for AgSbF6-Catalyzed Reactions
using Diarylmethanols
reactions presented in this manuscript took more time
to complete and the yields are comparatively less in
most of the cases. However this reaction resulted in
better yields with diarylmethanols having electron-
withdrawing halide groups. Overall the catalytic
nature of this reaction makes it superior.
Diarylmethanol (12, 1.2 equiv.) was weighed into a clean
and dry round-bottom flask. Dichloromethane/DCE (3 mL
per 0.5 mmol of 1), ketone (1, 1 equiv.), trimethyl orthofor-
mate (2 equiv.) were added and the mixture was stirred until
it become a homogenous solution. Then AgSbF6 (10 mol%)
While working on the a-propargylation reaction we was added under nitrogen and the reaction mixture was re-
fluxed under a nitrogen atmosphere until completion of the
reaction. After completion of the reaction, the solvent was
evaporated and the crude product was directly loaded on
a silica gel column. Mixtures of ethyl acetate and hexanes
were used as eluents to get the pure products. The data of
new compounds are reported here and some of the com-
pounds synthesized in this work were reported in the
literature.[6c,12,13]
noticed the formation of furan derivative 14 in 20%
yield along with the expected propargylated product
3d when 1a and 2b were treated in the presence of tri-
methyl orthoformate and catalytic AgOTf for 4 days.
Our repeated attempts to get a better yield of the
furan product in the above reaction under different
conditions such as heating at higher temperature in
sealed tube, changing the solvent etc. did not help
much. We then used the optimized conditions estab-
1,3,5-Triphenylpent-4-yn-1-one (3a):[12i] Yield: 70%;
1H NMR (400 MHz, CDCl3): d=7.96 (d, J=6.8 Hz, 2H),
lished by Zhan et al. for the cyclization step after al- 7.56–7.53 (m, 3H), 7.46–7.42 (m, 2H), 7.36–7.32 (m, 4H),
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
7
ÞÞ
These are not the final page numbers!

FULL PAPERS
Naganaboina Naveen et al.
7.26–7.22 (m, 4H), 4.65 (dd, J=7.6 Hz, 6.4 Hz, 1H), 3.67
(dd, J=16.4 Hz, 7.6 Hz, 1H) 3.41 (dd, J=16.4 Hz, 6 Hz,
1H); 13C NMR (100 MHz, CDCl3): d=197.2, 141.3, 136.9,
133.3, 131.7, 128.8, 128.7, 128.3, 128.2, 127.9, 127.7, 127.2,
123.5, 90.8, 83.4, 47.4, 33.8.
3-(4-Methoxyphenyl)-5-phenyl-1-(para-tolyl)pent-4-yn-1-
one (3g): Yield: 86%; thick colourless gummy liquid; IR
(neat): n=3059, 2957, 1682, 1510, 1249, 1035, 758, 692 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=7.85 (d, J=8.4 Hz, 2H),
7.42 (dd, J=6.8 Hz, 2.0 Hz, 2H), 7.36–7.34 (m, 2H), 7.25–
7.21 (m, 5H), 6.87 (dd, J=6.8 Hz, 2 Hz, 2H), 4.58 (t, J=
7.2 Hz, 1H), 3.76 (m, 3H), 3.59 (dd, J=16.4 Hz, 7.6 Hz,
1H), 3.36 (dd, J=16.4 Hz, 7.2 Hz, 1H), 2.37 (s, 3H);
13C NMR (100 MHz, CDCl3): d=196.9, 158.6, 144.1, 134.5,
133.5, 131.7, 129.4, 128.7, 128.4, 128.2, 127.9, 123.5, 114.1,
91.3, 83.1, 55.3, 47.3, 33.0, 21.7; HR-MS (ESI): m/z=
355.1698, calculated for C25H22O2 [M+H]+: 355.1698.
1-(4-Iodophenyl)-3,5-diphenylpent-4-yn-1-one (3b): Yield:
68%; light brown coloured solid; mp 106–1088C; IR (KBr):
n=3059, 1670, 1512, 758, 692 cmÀ1 1H NMR (400 MHz,
;
CDCl3): d=7.81 (d, J=8.4 Hz, 2H), 7.66 (d, J=8.4 Hz, 2H),
7.50 (d, J=7.2 Hz, 2H), 7.38–7.32 (m, 4H), 7.28–7.24 (m,
4H), 4.61 (dd, J=7.6 Hz, 6.4 Hz, 1H), 3.60 (dd, J=16.4 Hz,
8.0 Hz, 1H) 3.35 (dd, J=16.4 Hz, 6.4 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d=196.6, 141.1, 138.0, 136.2, 131.7,
129.7, 128.8, 128.3, 128.1, 127.7, 127.3, 123.3, 101.4, 90.6,
83.6, 47.2, 33.8; HR-MS (ESI): m/z=437.0402, calculated
for C23H17IO [M+H]+: 437.0402.
1-(Benzo[d][1,3]dioxol-5-yl)-3-(4-methoxyphenyl)-5-phe-
nylpent-4-yn-1-one (3h): Yield: 88%; light coloured brown
gel; IR (neat): n=2966, 1678, 1510, 1251, 1037, 758,
692 cmÀ1 1H NMR (400 MHz, CDCl3): d=7.53 (dd, J=
;
1-(Naphthalen-2-yl)-3,5-diphenylpent-4-yn-1-one
Yield: 55%; light yellow coloured solid; mp 110–1128C; IR
(KBr): n=3057, 1671, 1594, 1030, 756, 695 cmÀ1 1H NMR
(3c):
8.4 Hz, 2 Hz, 1H), 7.43–7.40 (m, 3H), 7.37–7.35 (m, 2H),
7.25–7.24 (m, 3H), 6.87 (dd, J=6.8 Hz, 2 Hz, 2H), 6.80 (d,
J=8.4 Hz, 1H), 5.99 (s, 2H), 4.56 (t, J=7.2 Hz, 1H), 3.77 (s,
3H), 3.53 (dd, J=16.4 Hz, 7.6 Hz, 1H), 3.3 (dd, J=16.4 Hz,
6.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=195.4, 158.6,
151.9, 148.3, 133.4, 131.8, 131.7, 128.7, 128.2, 127.9, 124.6,
123.5, 114.1, 108.1, 107.9, 101.9, 91.3, 83.2, 55.4, 47.2, 33.2;
HR-MS (ESI): m/z=385.1440, calculated for C25H20O4 [M+
H]+: 385.1440.
;
(400 MHz, CDCl3): d=8.44 (s, 1H), 8.02 (dd, J=8.8 Hz,
1.2 Hz, 1H), 7.90 (d, J=8.0 Hz, 1H), 7.86–7.82 (m, 2H),
7.58–7.55 (m, 3H), 7.51–7.49 (m, 1H), 7.37–7.34 (m, 4H),
7.27–7.25 (m, 1H), 7.24–7.20 (m, 3H), 4.73–4.69 (m, 1H),
3.79 (dd, J=16.4 Hz, 8.0 Hz, 1H), 3.53 (dd, J=16.4 Hz,
6.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=197.1, 141.4,
135.7, 134.2, 132.5, 131.7, 130.1, 129.6, 128.8, 128.6, 128.5,
128.2, 127.9, 127.8, 127.7, 127.2, 126.8, 123.9, 123.4, 90.9,
83.4, 47.4, 33.9; HR-MS (ESI); m/z=383.1412, calculated
for C27H20O [M+Na]+: 383.1412.
1-(4-Bromophenyl)-3-(4-methoxyphenyl)-5-phenylpent-4-
yn-1-one (3i): Yield: 84%; yellow coloured solid; mp 144–
1468C; IR (KBr): n=3059, 2957, 1687, 1510, 1251, 1033,
1
758, 692 cmÀ1; H NMR (400 MHz, CDCl3): d=7.80 (d, J=
3-(4-Methoxyphenyl)-1,5-diphenylpent-4-yn-1-one (3d):[13]
8.4 Hz, 2H), 7.57 (d, J=8.4 Hz, 2H), 7.41 (d, J=8.4 Hz,
2H), 7.35–7.33 (m, 2H), 7.26–7.24 (m, 3H), 6.87 (d, J=
8.8 Hz, 2H), 4.56 (t, J=7.2 Hz, 1H), 3.78 (s, 3H), 3.57 (dd,
J=16.4 Hz, 8.0 Hz, 1H), 3.34 (dd, J=16.8 Hz, 6.4 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=196.4, 158.8, 135.7, 133.2,
132.0, 131.7, 129.8, 129.5, 128.7, 128.2, 128.0, 123.4, 114.2,
90.9, 83.4, 55.4, 47.4, 33.1; HR-MS (ESI): m/z=419.0647,
calculated for C24H19BrO2 [M+H]+: 419.0647.
1
Yield: 74%; H NMR (400 MHz, CDCl3): d=7.96–7.94 (m,
2H), 7.57–7.53 (m, 1H), 7.46–7.42 (m, 4H) 7.36–7.34 (m,
2H), 7.26–7.24 (m, 3H), 6.89–6.87 (m, 2H), 4.59 (t, J=
7.2 Hz, 1H), 3.78 (s, 3H), 3.63 (dd, J=16.8 Hz, 7.2 Hz, 1H),
3.39 (dd, J=16.8 Hz, 6.8 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d=197.4, 158.7, 136.9, 133.4, 133.3, 131.7, 128.7,
128.3, 128.2, 127.9, 123.5, 114.2, 91.2, 83.2, 55.4, 47.5, 33.0.
1-(4-Iodophenyl)-3-(4-methoxyphenyl)-5-phenylpent-4-yn-
1-one (3e): Yield: 81%; yellow coloured solid, mp 112–
1148C; IR (KBr): n=2953, 1676, 1490, 1249, 1030, 761,
1-(2-Bromophenyl)-3-(4-methoxyphenyl)-5-phenylpent-4-
yn-1-one (3j): Yield: 45%; light brown coloured gummy gel;
IR (neat): n=3055, 2984, 1699, 1512, 1265, 738, 704 cmÀ1
;
695 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=7.82–7.80 (m,
1H NMR (400 MHz, CDCl3): d=7.58 (d, J=7.6 Hz, 1H),
7.41–7.36 (m, 4H), 7.32 (d, J=4.0 Hz, 2H), 7.28–7.25 (m,
4H), 6.88–6.86 (m, 2H), 4.52 (dd, J=16.4 Hz, 6.8 Hz, 1H),
3.79 (s, 3H), 3.53 (dd, J=16.4 Hz, 8.4 Hz, 1H), 3.39 (dd, J=
16.4 Hz, 6.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=
201.4, 158.7, 141.5, 133.6, 132.7, 131.7, 131.6, 128.9, 128.6,
128.2, 127.9, 127.4, 123.3, 118.7, 114.0, 90.5, 83.5, 55.3, 51.2,
33.4; HR-MS (ESI): m/z=419.0648, calculated for
C24H19BrO2 [M+H]+: 419.0647.
2H), 7.67–7.65 (m, 2H), 7.41 (d, J=8.8 Hz, 2H), 7.35–7.33
(m, 2H), 7.27–7.26 (m, 3H), 6.88–6.86 (m, 2H), 4.57–4.54
(m, 1H), 3.79 (s, 3H), 3.55 (dd, J=16.4 Hz, 7.6 Hz, 1H),
3.35 (dd, J=16.4 Hz, 6.4 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d=196.8, 158.8, 138.1, 136.3, 133.2, 131.8, 129.8,
128.7, 128.3, 128.1, 123.5, 114.2, 101.4, 90.9, 83.5, 55.5, 47.4,
33.2; HR-MS (ESI): m/z=467.0507, calculated for
C24H19IO2 [M+H]+: 467.0508.
1,3-Bis(4-methoxyphenyl)-5-phenylpent-4-yn-1-one (3f):
Yield: 75%; light yellow coloured solid; mp 102–1048C; IR
3-(4-Methoxyphenyl)-5-phenyl-1-(thiophen-2-yl)pent-4-
yn-1-one (3k): Yield: 60%; brown coloured solid; mp 99–
1018C; IR (KBr): n=3078, 2957, 1662, 1512, 1249, 1033,
(KBr): n=3061, 2957, 1676, 1510, 1253, 1032, 758, 692 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=7.95–7.93 (m, 2H), 7.42 (d,
J=8.4 Hz, 2H), 7.36–7.34 (m, 2H), 7.25–7.23 (m, 3H), 6.91–
6.86 (m, 4H), 4.58 (t, J=7.2 Hz, 1H), 3.83 (d, J=0.8 Hz,
3H), 3.77 (d, J=1.2 Hz, 3H), 3.57 (dd, J=16.4 Hz, 7.6 Hz,
1H), 3.33 (dd, J=16.4 Hz, 6.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d=195.8, 163.6, 158.6, 133.5, 131.7,
130.6, 130.1, 128.7, 128.2, 127.9, 123.5, 114.1, 113.8, 91.4,
83.1, 55.5, 55.4, 47.1, 33.1; HR-MS (ESI): m/z=371.1647,
calculated for C25H22O3 [M+H]+: 371.1647.
727, 692 cmÀ1; H NMR (400 MHz, CDCl3): d=7.69 (d, J=
1
3.6 Hz, 1H), 7.61 (d, J=4.8 Hz, 1H), 7.42 (d, J=8.4 Hz,
2H), 7.35–7.32 (m, 2H), 7.25–7.24 (m, 3H), 7.08 (t, J=
4.8 Hz, 1H), 6.87 (d, J=8.4 Hz, 2H), 4.56 (t, J=7.2 Hz,
1H), 3.77 (s, 3H), 3.51 (dd, J=16 Hz, 8.0 Hz, 1H), 3.30 (dd,
J=16.0 Hz, 6.8 Hz, 1H). 13C NMR (100 MHz, CDCl3): d=
190.2, 158.7, 144.4, 134.1, 133.1, 132.4, 131.7, 128.7, 128.2,
127.9, 123.4, 114.2, 90.8, 83.6, 55.4, 48.1, 33.4; HR-MS (ESI):
m/z=369.0930, calculated for C22H18O2S [M+Na]: 369.0925.
8
asc.wiley-vch.de
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

FULL PAPERS
Silver Hexafluoroantimonate-Catalyzed Direct a-Alkylation
3-(4-Methoxyphenyl)-2-methyl-1,5-diphenylpent-4-yn-1-
2.08–2.07 (m, 1H), 1.97–1.94 (m, 1H), 1.89–1.87 (m, 1H),
1.74–1.63 (m, 2H); 13C NMR (100 MHz, CDCl3): d=209.7,
144.2, 131.8, 128.3, 128.1, 126.8, 125.5, 124.1, 123.4, 88.5,
84.6, 57.4, 42.2, 32.6, 29.8, 27.5, 25; HR-MS (ESI): m/z=
317.0980, calculated for C19H18OS [M+Na]+: 317.0976.
one (3l): Yield: 61%; colourless gel; IR (neat): n=3061,
1
2970, 1682, 1510, 1448, 1251, 1033, 758, 692 cmÀ1; H NMR
(400 MHz, CDCl3): d=8.06 (d, J=7.2 Hz, 0.7H), 7.79–7.77
(m, 2H), 7.57–7.50 (m, 0.4H), 7.50–7.43 (m, 4H), 7.39–7.33
(m, 5H), 7.29–7.28 (m, 3H), 7.18–7.12 (m, 1H), 7.09–7.07
(m, 0.7H), 6.91–6.88 (m, 0.7H), 6.79–6.75 (m, 2H), 4.35 (d,
J=8.8 Hz, 1H), 4.11 (d, J=9.6 Hz, 0.3H), 3.94–3.85 (m,
1.45H), 3.80 (s, 1H), 3.71 (s, 3H), 1.45 (d, J=6.8 Hz, 3H),
1.04 (d, J=7.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=
203.3, 202.5, 158.9, 158.6, 137.4, 136.8, 133.2, 133.0, 132.6,
131.7, 131.6, 131.4, 129.7, 129.4, 129.3, 128.7, 128.6, 128.3,
128.2, 128.1, 128.0, 127.8, 123.6, 123.4, 114.1, 113.9, 91.0,
90.1, 84.7, 83.7, 55.4, 55.3, 48.2, 47.8, 40.8, 40.6, 16.6, 16.0;
HR-MS (ESI): m/z=355.1698, calculated for C25H22O2 [M+
H]+: 355.1698.
1,5-Diphenyl-3-(thiophen-2-yl)pent-4-yn-1-one
(3q):[13]
1
Yield: 46%; H NMR (400 MHz, CDCl3): d=7.98–7.90 (m,
2H), 7.59–7.55 (m, 1H), 7.48–7.45 (m, 2H), 7.40–7.37 (m,
2H), 7.28–7.26 (m, 3H), 7.19 (dd, J=4.8 Hz, 1.2 Hz, 1H),
7.12–7.09 (m, 1H), 6.94 (t, J=4.4 Hz, 1H), 4.96 (t, J=
6.8 Hz, 1H), 3.70 (dd, J=16.8 Hz, 7.2 Hz, 1H), 3.55 (dd, J=
16.8 Hz, 6.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=
196.7, 144.6, 136.7, 133.4, 131.7, 128.7, 128.3, 128.2, 128.1,
126.8, 124.9, 124.3, 123.1, 90.1, 82.9, 47.5, 28.9.
1-(4-Methoxyphenyl)-5-phenyl-3-(thiophen-2-yl)pent-4-
yn-1-one (3r): Yield: 51%; light brown coloured liquid; IR
2-Ethylidene-3-(4-methoxyphenyl)-1,5-diphenylpent-4-yn-
1-one (3m): Yield: 55%; colourless gel; IR (neat): n=3059,
(neat): n=1676, 1490, 1265, 1057, 767, 706 cmÀ1 1H NMR
;
(400 MHz, CDCl3): d=7.96–7.94 (m, 2H), 7.39–7.37 (m,
2H), 7.26–7.24 (m, 3H), 7.16 (dd, J=5.2 Hz, 1.2 Hz, 1H),
7.09–7.08 (m, 1H), 6.93–6.88 (m, 3H), 4.94 (t, J=6.8 Hz,
1H), 3.82 (s, 3H), 3.63 (dd, J=16.8 Hz, 6.8 Hz, 1H), 3.48
(dd, J=16.8 Hz, 6.8 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d=195.2, 163.7, 144.8, 131.7, 130.6, 129.8, 128.2, 128.1, 126.8,
126, 124.9, 124.3, 123.2, 113.8, 90.4, 82.9, 55.5, 47.1; HR-MS
(ESI): m/z=369.0945, calculated for C22H18O2S [M+Na]+:
369.0925.
1
2964, 1678, 1510, 1251, 758, 692 cmÀ1; H NMR (400 MHz,
CDCl3): d=8.08 (d, J=7.2 Hz, 1H), 7.72 (d, J=7.6 Hz, 2H),
7.59–7.56 (m, 0.67H), 7.51–7.48 (m, 1H), 7.47–7.43 (m, 3H),
7.36–7.28 (m, 8H), 7.17–7.10 (m, 1.8H), 6.98–6.97 (m,
1.2H), 6.90–6.88 (m, 1H), 6.74–6.72 (m, 2H), 4.29 (d, J=
9.6 Hz, 1H), 4.06 (d, J=9.6 Hz, 0.6H), 3.87–3.84 (m, 1.7H),
3.80 (s, 2H), 3.69 (s, 3H), 2.10–2.08 (m, 2H), 1.74–1.67 (m,
0.6H), 1.46–1.40 (m, 0.7H), 0.88 (t, J=7.2 Hz, 3H), 0.74 (t,
J=7.2 Hz, 1.8H); 13C NMR (100 MHz, CDCl3): d=203.8,
202.8, 158.9, 158.5, 139.0, 138.3, 133.1, 132.9, 132.4, 131.7,
131.5, 129.6, 129.4, 128.7, 128.6, 128.5, 128.3, 128.1, 128.0,
127.8, 123.7, 123.4, 114.1, 113.9, 90.8, 90.5, 84.5, 83.9, 55.4,
55.3, 54.6, 54.5, 40.6, 39.9, 25.1, 24.3, 11.9, 11.5; HR-MS
(ESI): m/z=369.1854, calculated for C26H24O2 [M+H]+:
369.1855.
4-(4-Methoxyphenyl)-6-(para-tolyl)hex-5-yn-2-one
(3s):
Yield: 59%; colourless liquid; IR (neat): n=2997, 1720,
1
1512, 1249, 756 cmÀ1; H NMR (400 MHz, CDCl3): d=7.36
(d, J=8.8 Hz, 2H), 7.30 (d, J=8.0 Hz, 2H), 7.09 (d, J=
8.0 Hz, 2H), 6.87 (d, J=8.8 Hz, 2H), 4.34 (t, J=7.2 Hz,
1H), 3.79 (s, 3H), 3.03 (dd, J=16.4 Hz, 8 Hz, 1H), 2.86 (dd,
J=16.4 Hz, 6.8 Hz, 1H), 2.33 (s, 3H), 2.16 (s, 3H);
13C NMR (100 MHz, CDCl3): d=206.2, 158.7, 138.1, 133.2,
131.6, 129.1, 128.6, 120.4, 114.2, 90, 83.3, 55.4, 52.2, 32.9,
30.8, 21.6; HR-MS (ESI): m/z=315.1362, calculated for
C20H20O2 [M+Na]+: 315.1361.
4-(4-Methoxyphenyl)-6-phenylhex-5-yn-2-one (3n): Yield:
70%; colourless liquid; IR (neat): n=3059, 2957, 1716, 1512,
1
1251, 1032, 758, 692 cmÀ1; H NMR (400 MHz, CDCl3): d=
7.42–7.39 (m, 2H), 7.37–7.34 (m, 2H), 7.28–7.25 (m, 3H),
6.88–6.86 (m, 2H), 4.36 (t, J=7.2 Hz, 1H), 3.79 (s, 3H), 3.04
(dd, J=16.4 Hz, 8.0 Hz, 1H), 2.87 (dd, J=16.4 Hz, 6.4 Hz,
1H), 2.16 (s, 3H). 13C NMR (100 MHz, CDCl3): d=206.2,
158.7, 133.1, 131.7, 128.6, 128.3, 128.1, 123.5, 114.2, 90.8,
83.2, 55.4, 52.1, 32.8, 30.8; HR-MS (ESI): m/z=279.1385,
calculated for C19H18O2 [M+H]+: 279.1385.
3-(4-Methoxyphenyl)-1-phenyl-5-(para-tolyl)pent-4-yn-1-
one (3t): Yield: 50%; light yellow coloured solid; mp 90–
928C; IR (KBr): n=2832, 1687, 1517, 1260, 761, 684 cmÀ1
;
1H NMR (400 MHz, CDCl3): d=7.95 (d, J=7.6 Hz, 2H),
7.55 (t, J=7.2 Hz, 1H), 7.46–7.42 (m, 4H), 7.24 (d, J=
7.6 Hz, 2H), 7.05 (d, J=8.0 Hz, 2H), 6.87 (d, J=7.6 Hz,
2H), 4.58 (t, J=7.2 Hz, 1H), 3.78 (s, 3H), 3.62 (dd, J=
16.4 Hz, 7.6 Hz, 1H), 3.38 (dd, J=16.4 Hz, 6.4 Hz, 1H), 2.31
(s, 3H); 13C NMR (100 MHz, CDCl3): d=197.5, 158.7, 137.9,
137.1, 133.6, 133.3, 131.6, 129.0, 128.7, 128.7, 128.4, 120.5,
114.2, 90.4, 83.3, 55.4, 47.6, 33.1, 21.5; HR-MS (ESI): m/z=
355.1698, calculated for C25H22O2 [M+H]+: 355.1698.
6-Phenyl-4-(thiophen-2-yl)hex-5-yn-2-one (3o): Yield:
56%; brown coloured gummy liquid; IR (neat): n=3062,
2920, 1714, 1495, 1358, 1067, 755, 689 cmÀ1
;
1H NMR
(400 MHz, CDCl3): d=7.44–7.42 (m, 2H), 7.30- 7.28 (m,
3H), 7.20–7.18 (m, 1H), 7.05–7.04 (m, 1H), 6.94 (dd, J=
5.2 Hz, 1.2 Hz, 1H), 4.71(t, J=6.8 Hz, 1H), 3.13(dd, J=
16.8 Hz, 7.2 Hz, 1H), 3.01 (dd, J=16.8 Hz, 6.8 Hz, 1H), 2.21
(s, 3H); 13C NMR (100 MHz, CDCl3): d=205.3, 144.3, 131.7,
128.3, 128.2, 126.8, 124.9, 124.3, 123, 89.7, 82.9, 52, 30.6, 28.7;
HR-MS (ESI): m/z=277.0661, calculated for C16H14OS
[M+Na]+: 277.0663.
(E)-4,6-Bis(4-chlorophenyl)hex-5-en-2-one (11m): Yield:
56%; colourless gel; IR (KBr): n=2997, 1720, 1512, 1249,
756 cmÀ1 1H NMR (400 MHz, CDCl3): d=7.30–7.27 (m,
;
2H), 7.24–7.20 (m, 4H), 7.19–7.17 (m, 2H), 6.32–6.21 (m,
2H), 4.08–4.03 (m, 1H), 2.97–2.86 (m, 2H), 2.11 (s, 3H);
13C NMR (100 MHz, CDCl3): d=206.4, 141.3, 135.5, 133.2,
132.7, 132.6, 129.3, 129.2, 128.9, 128.8, 127.6, 49.2, 43.2, 30.8;
HR-MS (ESI): m/z=341.0478, calculated for C18H16Cl2O
[M+Na]+: 341.0476.
2-[3-Phenyl-1-(thiophen-2-yl)prop-2-yn-1-yl]cyclohexan-
ACHTUNGTRENNUNG
;
(400 MHz, CDCl3): d=7.47–7.45 (m, 2H), 7.31–7.29 (m,
3H), 7.19 (dd, J=5.2 Hz, 0.8 Hz, 1H), 7.09–7.08 (m, 1H),
6.96 (dd, J=5.2 Hz, 3.6 Hz, 1H), 4.91(d, J=4.4 Hz, 1H),
2.73–2.71 (m, 1H), 2.53–2.49 (m, 1H), 2.36–2.29 (m, 2H),
3,3-Bis(4-chlorophenyl)-1-phenylpropan-1-one (13m):[21f]
Yield: 74%; 1H NMR (400 MHz, CDCl3): d=7.95 (d, J=
7.6 Hz, 2H), 7.59–7.56 (m, 1H), 7.48–7.45 (m, 2H), 7.26 (d,
J=7.6 Hz, 4H), 7.19 (d, J=7.6 Hz, 4H), 4.81 (t, J=7.2 Hz,
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
9
ÞÞ
These are not the final page numbers!

FULL PAPERS
Naganaboina Naveen et al.
1H), 3.70 (d, J=7.2 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 197.4, 142.3, 136.8, 133.4, 132.5, 129.2, 128.9, 128.8, 128.1,
44.7, 44.5.
2014, 53, 225; c) L. K. M. Chan, D. L. Poole, D. Shen,
M. P. Healy, T. J. Donohoe, Angew. Chem. 2014, 126,
780; Angew. Chem. Int. Ed. 2014, 53, 761; d) G. Xu, Q.
Li, J. Feng, Q. Liu, Z. Zhang, X. Wang, X. Zhang, X.
Mu, ChemSusChem 2014, 7, 105; e) X. Pan, M. Li, Y.
Gu, Chem. Asian J. 2014, 9, 268; f) N. Kalutharage,
C. S. Yi, Angew. Chem. 2013, 125, 13896; Angew.
Chem. Int. Ed. 2013, 52, 13651.
Preparation of 2-Benzyl-3-(4-methoxyphenyl)-5-
phenylfuran (14)
1-(4-Methoxyphenyl)-3-phenylprop-2-yn-1-ol 2b (50 mg,
0.21 mmol) was weighed into a clean and dry round-bottom
[4] For the alkylation of ketones with alcohols, see: a) X.
Huo, G. Yang, D. Liu, Y. Liu, I. D. Gridnev, W. Zhang,
Angew. Chem. 2014, 126, 6894; Angew. Chem. Int. Ed.
2014, 53, 6776; b) L. Song, Q.-X. Guo, X.-C. Li, J. Tian,
Y.-G. Peng, Angew. Chem. 2012, 124, 1935; Angew.
Chem. Int. Ed. 2012, 51, 1899; c) G. Guillena, D. J.
Ramꢂn, M. Yus, Angew. Chem. 2007, 119, 2410;
Angew. Chem. Int. Ed. 2007, 46, 2358; d) Z.-T. Weng,
Y. Li, S.-K. Tian, J. Org. Chem. 2011, 76, 8095; e) L.
Zhang, L. Cui, X. Li, J. Li, S. Luo, J.-P. Cheng, Chem.
Eur. J. 2010, 16, 2045; f) M. Trifonidou, C. G. Kokotos,
Eur. J. Org. Chem. 2012, 1563; for representative exam-
ples of the a-alkylation of aldehydes, see: g) B. Xu, Z.-
L. Guo, W.-Y. Jin, Z.-P. Wang, Y.-G. Peng, Q.-X. Guo,
Angew. Chem. 2012, 124, 1083; Angew. Chem. Int. Ed.
2012, 51, 1059; h) J. Xiao, Org. Lett. 2012, 14, 1716; i) J.
Xiao, K. Zhao, T.-P. Loh, Chem. Asian J. 2011, 6, 2890;
j) C. Xing, H. Sun, J. Zhang, G. Li, Y. R. Chi, Chem.
Eur. J. 2011, 17, 12272; k) P. G. Cozzi, F. Benfatti, L.
Zoli, Angew. Chem. 2009, 121, 1339; Angew. Chem. Int.
Ed. 2009, 48, 1313; l) F. Benfatti, E. Benedetto, P. G.
Cozzi, Chem. Asian J. 2010, 5, 2047.
[5] a) H. Mayr, B. Kempf, A. R. Ofial, Acc. Chem. Res.
2003, 36, 66; b) H. Mayr, A. R. Ofial, J. Phys. Org.
Chem. 2008, 21, 584; c) H. Mayr, T. Bug, M. F. Gotta,
N. Hering, B. Irrgang, B. Janker, B. Kempf, R. Loos,
A. R. Ofial, G. Remennikov, H. Schimmel, J. Am.
Chem. Soc. 2001, 123, 9500; d) J. Ammer, C. Nolte, H.
Mayr, J. Am. Chem. Soc. 2012, 134, 13902.
[6] a) R. B. Kothapalli, R. Niddana, R. Balamurugan, Org.
Lett. 2014, 16, 1278; b) S. Manojveer, R. Balamurugan,
Org. Lett. 2014, 16, 1712; c) S. R. Koppolu, N. Naveen,
R. Balamurugan, J. Org. Chem. 2014, 79, 6069; d) S.
Manojveer, R. Balamurugan, Chem. Commun. 2014,
50, 9925.
flask under
a nitrogen atmosphere. Dichloromethane
(2 mL), acetophenone 1a (21 mg, 0.175 mmol), trimethyl or-
thoformate (37 mg, 0.35 mmol) were added and the mixture
was stirred until it became a homogenous solution. Then
AgSbF6 (6 mg, 10 mol%) was added and the reaction mix-
ture was stirred at room temperature under a nitrogen at-
mosphere for 14 h. Then the solvent was evaporated under
reduced pressure. Dry toluene (2 mL) and PTSA monohy-
drate (33 mg, 0.175 mmol) were added to the crude product
and the mixture was heated to 1108C for 2 h. The solvent
was evaporated and the crude product was directly loaded
on a silica gel column. Mixtures of ethyl acetate and hex-
anes were used as eluents to get the pure 2-benzyl-3-(4-me-
thoxyphenyl)-5-phenylfuran as brown coloured liquid; yield:
25 mg (42%). IR (KBr): n=3059, 2922, 1510, 1447, 1258,
1098, 1029, 754 cmÀ1; H NMR (400 MHz, CDCl3): d=7.60–
1
7.58 (m, 2H), 7.31–7.27 (m, 3H), 7.26 À7.24 (m, 2H), 7.22–
7.21 (m, 2H), 7.19–7.15 (m, 3H), 6.86–6.85 (m, 2H), 6.71 (s,
1H), 4.10 (s, 2H), 3.75 (s, 3H); 13C NMR (100 MHz,
CDCl3): d=158.7, 152.4, 148.5, 138.8, 130.9, 128.9, 128.7,
128.5, 127.3, 126.5, 126.4, 124.2,114.2, 106.8, 55.4, 33; HR-
MS (ESI): m/z=341.1541, calculated for C24H20O2 [M+H]+:
341.1542.
Acknowledgements
The authors thank Department of Science and Technology
(DST), India for funding this work. NN and SRK thank
Council of Scientific and Industrial Research (CSIR) for fel-
lowships.
References
[7] For a similar proposal, see: a) R. Chakraborti, B. C.
Ranu, U. R. Ghatak, J. Org. Chem. 1985, 50, 5268;
b) R. Dasgupta, B. Ranu, U. R. Ghatak, Indian. J.
Chem. 1983, 22, 619; c) R. Chakrborti, B. Ranu, U. R.
Ghatak, Synth. Commun. 1987, 17, 1539.
[1] a) W. S. Matthews, J. E. Bares, J. E. Bartmess, F. G.
Bordwell, F. J. Cornforth, G. E. Drucker, Z. Margolin,
R. J. McCallum, G. J. McCollum, N. R. Vanier, J. Am.
Chem. Soc. 1975, 97, 7006; b) pKa =18–20 in H2O;
D. H. Ripin, D. A. Evans, http://www2.lsdiv.harvard.
edu/labs/evans/pdf/evans_pKa_table.pdf.
[2] a) F. A. Carey, R. J. Sundberg Advanced Organic
Chemistry, Part B, Springer, Berlin, Heidelberg, 2008,
pp 1–56; b) C. H. Heathcock, The Aldol Reaction: Acid
and General Base Catalysis, in: Comprehensive Organic
Synthesis 2, (Eds.: B. M. Trost, I. Fleming), Elsevier
Science, Oxford, 1991, pp 133–179; c) S. C. Welch, S.
Chayabunjonglerd, J. Am.Chem. Soc. 1979, 101, 6768;
d) K. Sisido, S. Kurozumi, K. Utimoto, J. Org. Chem.
1969, 34, 2661.
[8] a) T. Wang, X.-L. Chen, L. Chen, Z.-P. Zhan, Org. Lett.
2011, 13, 3324; b) R. Sanz, D. Miguel, A. Martinez,
J. M. Alvarez-Gutierrez, F. Rodriguez, Org. Lett. 2007,
9, 727; c) Y. Nishibayashi, M. Yoshikawa, Y. Inada,
M. D. Milton, M. Hidai, S. Uemura, Angew. Chem.
2003, 115, 2785; Angew. Chem. Int. Ed. 2003, 42, 2681.
[9] a) E. Rafiee, M. Khodayari, M. Kahrizi, R. Tayebee, J.
Mol. Catal. A: 2012, 358, 121; b) P. N. Chatterjee, S.
Roy, Tetrahedron 2011, 67, 4569; c) A. Zhu, L. Li, J.
Wang, K. Zhou, Green Chem. 2011, 13, 1244; d) P. N.
Liu, F. Xia, Q. W. Wang, Y. J. Ren, J. Q. Chen, Green
Chem. 2010, 12, 1049; e) P. N. Liu, L. Dang, Q. W.
Wang, S. L. Zhao, F. Xia, Y. J. Ren, X. Q. Gong, J. Q.
Chen, J. Org. Chem. 2010, 75, 5017; f) C. R. Reddy, J.
[3] a) F. Mo, G. Dong, Science. 2014, 345, 68–72; b) Q. Xu,
J. Chen, H. Tian, X. Yuan, S. Li, C. Zhou, J. Liu,
Angew. Chem. 2014, 126, 229; Angew. Chem. Int. Ed.
10
asc.wiley-vch.de
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

FULL PAPERS
Silver Hexafluoroantimonate-Catalyzed Direct a-Alkylation
Vijaykumar, R. Grꢃe, Synthesis 2010, 3715; g) K. Funa-
biki, T. Komeda, Y. Kubota, M. Matsui, Tetrahedron
2009, 65, 7457; h) Y.-m. Pan, S.-y. Zhao, W.-h. Ji, Z. J.-
p. Zhan, J. Comb. Chem. 2009, 11, 103; i) J. S. Yadav,
B. V. S. Reddy, T. Pandurangam, K. V. R. Rao, K. Pra-
neeth, G. G. K. S. N. Kumar, C. Madavi, A. C. Kunwar,
Tetrahedron Lett. 2008, 49, 4296; j) G.-W. Wang, Y.-B.
Shen, X.-L. Wu, Eur. J. Org. Chem. 2008, 4999; k) W.
Huang, J. Wang, Q. Shen, X. Zhou, Tetrahedron Lett.
2007, 48, 3969; l) M. Rueping, B. J. Nachtsheim, A.
Kuenkel, Org. Lett. 2007, 9, 825; m) K. Motokura, N.
Nakagiri, T. Mizugaki, K. Ebitani, K. Kaneda, J. Org.
Chem. 2007, 72, 6006; n) M. Noji, Y. Konno, K. Ishii, J.
Org. Chem. 2007, 72, 5161; o) R. Sanz, D. Miguel, A.
Martꢄnez, J. M. ꢅlvarez-Gutiꢃrrez, F. Rodrꢄguez, Org.
Lett. 2007, 9, 2027; p) S. Shirakawa, S. Kobayashi, Org.
Lett. 2007, 9, 311; q) U. Jana, S. Biswas, S. Maiti, Tetra-
hedron Lett. 2007, 48, 4065; r) P. N. Liu, Z. Y. Zhou,
C. P. Lau, Chem. Eur. J. 2007, 13, 8610; s) M. Yasuda,
T. Somyo, A. Baba, Angew. Chem. 2006, 118, 807;
Angew. Chem. Int. Ed. 2006, 45, 793; t) K. Motokura,
N. Fujita, K. Mori, T. Mizugaki, K. Ebitani, K. Kaneda,
Angew. Chem. 2006, 118, 2667–2671; Angew. Chem. Int.
Ed. 2006, 45, 2605.
[14] For reviews, see a) G. W. Kabalka, M.-L. Yao, Curr.
Org. Synth. 2008, 5, 28; b) J. R. Green, Curr. Org.
Chem. 2001, 5, 809; c) T. J. J. Mꢆller, Eur. J. Org.
Chem. 2001, 2021; d) Y. Nishibayashi, Synthesis 2012,
489, and references cited therein; e) for SN1 type reac-
tions of chiral propargyl alcohols, see: D. Nitsch, S. M.
Huber, A. Pçthig, A. Narayanan, G. A. Olah, G. K.
Surya Prakash, T. Bach, J. Am. Chem. Soc. 2014, 136,
2851; for the stability of propargyl cation and its prop-
erties, see: f) G. A. Olah, R. J. Spear, P. W. Westerman,
J.-M. Denis, J. Am. Chem. Soc. 1974, 96, 5855; for Bi-,
Fe-catalyzed propargylic substitution, see: g) Z.-p.
Zhan, W.-z. Yang, R.-f. Yang, J-L. Yu, J.-p. Li, H.-j.
Liu, Chem. Commun. 2006, 3352; h) Z.-p. Zhan, J-L.
Yu, H.-j. Liu, Y.-y. Cui, W.-z. Yang, J.-p. Li, J. Org.
Chem. 2006, 71, 8298; for metal-free propargylic substi-
tution, see: i) R. Sanz, A. Martꢄnez, J. M. ꢅlvarez-Gu-
tiꢃrrez, F. Rodrꢄguez, Eur. J. Org. Chem. 2006, 1383.
[15] a) K. M. Nicholas, Acc. Chem. Res. 1987, 20, 207;
b) J. R. Green, Curr. Org. Chem. 2001, 5, 809; c) B. J.
Teobald, Tetrahedron 2002, 58, 4133.
[16] a) M. R. Luzung, F. D. Toste, J. Am. Chem. Soc. 2003,
125, 15760; b) J. J. Kennedy-Smith, L. A. Young, F. D.
Toste, Org. Lett. 2004, 6, 1325.
[17] a) M. Georgy, V. Boucard, J.-M. Campagne, J. Am.
Chem. Soc. 2005, 127, 14180; b) M. Georgy, V. Bou-
card, O. Debleds, C. Dal Zotto, J.-M. Campagne, Tetra-
hedron 2009, 65, 1758.
[18] a) M. N. Pennell, P. G. Turner, T. D. Sheppard, Chem.
Eur. J. 2012, 18, 4748; for silver-catalyzed allylic substi-
tution, see: b) M. Bandini, A. Eichholzer, P. Kotrusz,
M. Tragni, S. Troisi, A. Umani-Ronchi, Adv. Synth.
Catal. 2009, 351, 319; for silver-catalyzed benzylic sub-
stitution, see: c) B. Sreedhar, P. S. Reddy, M. A. Reddy,
B. Neelima, R. Arundhathi, Tetrahedron Lett. 2007, 48,
8174; for alkynophilicity of silver, see: d) Y. Yamamo-
to, J. Org. Chem. 2007, 72, 7817; e) M. Naodovic, Y. Ya-
mamoto, Chem. Rev. 2008, 108, 3132.
[10] a) Y. Nishibayashi, I. Wakiji, Y. Ishii, S. Uemura, M.
Hidai, J. Am. Chem. Soc. 2001, 123, 3393; b) Y. Nishi-
bayashi, I. Wakiji, M. Hidai, J. Am. Chem. Soc. 2000,
122, 11019; c) for an asymmetric version, see: Y. Inada,
Y. Nishibayashi, S. Uemura, Angew. Chem. 2005, 117,
7893; Angew. Chem. Int. Ed. 2005, 44, 7715; d) Y. Nish-
ibayashi, G. Onodera, Y. Inada, M. Hidai, S. Uemura,
Organometallics 2003, 22, 873.
[11] a) I. Matsuda, K.-i. Komori, K. Itoh, J. Am. Chem. Soc.
2002, 124, 9072; b) Z.-p. Zhan, S.-p. Wang, X.-b. Cai,
H.-j. Liu, J-L. Yu, Y.-y. Cui, Adv. Synth. Catal. 2007,
349, 2097; c) Z.-p. Zhan, X.-b. Cai, S.-p. Wang, J.-l. Yu,
H.-j. Liu, Y.-y. Cui, J. Org. Chem. 2007, 72, 9838; d) M.
Lin, L. Hao, R.-d. Ma, Z.-p. Zhan, Synlett 2010, 2345;
e) Y. Nishimoto, Y. Onishi, M. Yasuda, A. Baba,
Angew. Chem. 2009, 121, 9295; Angew. Chem. Int. Ed.
2009, 48, 9131; f) P. Fang, X.-L. Hou, Org. Lett. 2009,
11, 4612.
[12] a) J. Hooz, R. B. Layton, J. Am. Chem. Soc. 1971, 93,
7320; b) J. A. Sinclair, G. A. Molander, H. C. Brown, J.
Am. Chem. Soc. 1977, 99, 954; c) M. Kidwai, A. Jain, S.
Bhardwaj, Catal. Lett. 2011, 141, 183; d) H. Fujishima,
E.-I. Takada, S. Hara, A. Suzuki, Chem. Lett. 1992,
695; e) S. Bhanu, F. Scheinmann, J. Chem. Soc. Perkin
Trans. 1979, 1218; f) T. F. Knçpfel, E. M. Carreira, J.
Am. Chem. Soc. 2003, 125, 6054; g) F. Bertolini, S.
Woodward, Synlett 2009, 51; h) T. R. Wu, J. M. Chong,
J. Am. Chem. Soc. 2007, 129, 4908; i) I. Shibata, T.
Kano, N. Kanazawa, S. Fukuoka, A. Baba, Angew.
Chem. 2002, 114, 1447; Angew. Chem. Int. Ed. 2002, 41,
1389; j) L. Villarino, R. Garcꢄa-FandiÇo, F. Lꢂpez, J. L.
MascareÇas, Org. Lett. 2012, 14, 2996, and references
cited therein.
[19] P. Singh, P. Sharma, K. Bisetty, M. P. Mahajan, Arkivoc
2011, 55, and the references cited therein.
[20] a) J. S. Yadav, G. Kondaji, M. S. R. Reddy, P. Srihari,
Tetrahedron Lett. 2008, 49, 3810; b) J. P. Richard, K. B.
Williams, J. Am. Chem. Soc. 2007, 129, 6952; c) J. P. Ri-
chard, K. B. Williams, T. L. Amyes, J. Am. Chem. Soc.
1999, 121, 8403; d) J. Toullec, M. El-Alaoui, P. Kleffert,
Tetrahedron Lett. 1987, 28, 1889; e) C. A. Mackenzie,
J. H. Stocker, J. Org. Chem. 1955, 20, 1695.
[21] For the formation of g-alkenones from allylic alcohols,
see: a) I. Matsuda, S. Wakamatsu, K.-i. Komori, M. Tat-
suya, K. Itoh, Tetrahedron Lett. 2002, 43, 1043; b) Y.
Nurettin, Indian J. Chem. Sect. B: 1994, 33, 556;
c) B. B. Thompson, J. Montgomery, Org. Lett. 2011, 13,
3289; d) S. Oi, Y. Honma, Y. Inoue, Org. Lett. 2002, 4,
667; for an asymmetric version, see: e) M. Sugiura, M.
Tokudomi, M. Nakajima, Chem. Commun. 2010, 46,
7799, and the references cited therein; f) B. M. Trost,
P. E. Strege, J. Am. Chem. Soc. 1977, 99, 1649; g) B. M.
Trost, Chem. Rev. 1996, 96, 4387; h) J. Tsuji, H. Taka-
shi, M. Morikawa, Tetrahedron Lett. 1965, 6, 4387.
[13] C. A. Campos, J. B. Gianino, B. L. Ashfeld, Org. Lett.
2013, 15, 2656.
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
11
ÞÞ
These are not the final page numbers!

FULL PAPERS
12 Silver Hexafluoroantimonate-Catalyzed Direct a-Alkylation
of Unactivated Ketones
Adv. Synth. Catal. 2015, 357, 1 – 12
Naganaboina Naveen, Srinivasa Rao Koppolu,
Rengarajan Balamurugan*
12
asc.wiley-vch.de
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!