Neighboring Carbonyl Group Assisted Hydration of Unsymmetrical Aryl Alkynes Overriding Regular Selectivity

Article abstract of DOI:10.1002/ejoc.201900941

A mild and highly regioselective gold-catalyzed hydration of γ-acetoxy aryl alkynes leading to anti-Markovnikov products by the assistance of a neighboring carbonyl group is presented. The reaction procedure operates under room temperature conditions with

Full text of DOI:10.1002/ejoc.201900941

A Journal of
Accepted Article
Title: Neighboring Carbonyl Group Assisted Hydration of
Unsymmetrical Aryl Alkynes Overriding Regular Selectivity
Authors: Debendra Kumar Mohapatra, Kishor L. Mendhekar, Tapas R.
Pradhan, and N. Arjunreddy Mallampudi
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900941
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10.1002/ejoc.201900941
European Journal of Organic Chemistry
FULL PAPER
Neighboring
Carbonyl
Group
Assisted
Hydration
of
Unsymmetrical Aryl Alkynes Overriding Regular Selectivity
Kishor L. Mendhekar,[a,b] Tapas R. Pradhan,[a] N. Arjunreddy Mallampudi,[a] and Debendra K.
Mohapatra*[a,b]
Abstract: A mild and highly regioselective goldꢀcatalyzed hydration
of γꢀacetoxy aryl alkynes leading to antiꢀMarkovnikov products by
the assistance of a neighboring carbonyl group is presented. The
reaction procedure operates under room temperature conditions with
broad functional group tolerance in presence of more than
stoichiometric amount of water to access two different types of
acyloins in good to excellent yields. Acetate protected acyloins were
produced from primary and secondary substrates, while tertiary ones
react differently to give freeꢀacyloins under identical conditions. The
mechanistic pathways for such divergent functionalization were
deduced from isotopic mechanistic results.
Introduction
Regioselective
atom
economy
functionalization
of
unsymmetrical alkynes via catalytic activation has become an
enormously attractive strategy to bring in functionality of interest
in recent years.[1] Especially, the regioselective hydration of
alkynes to generate carbonyl compounds,[2] are often useful as
an advanced chemical intermediates for a number of important
molecules, provides most straightforward and efficient
methodology for an ideal synthesis. Traditionally, this
transformation is performed in the presence of a highly toxic
reagents such as mercury and/or excess amount of
concentrated sulfuric acid.[3] Some more advantageous methods
using various electrophilic metal catalysts such as Pt,[4] Fe,[5]
Pd,[6] Ir,[7] Ag,[8] Co,[9] Rh,[10] Ru[11] and Au,[12] with the latter being
an archetypal catalyst, have also been testified in recent years
for such transformation.
Scheme 1. The existing methods of hydration of unsymmetrical alkynes and
this method.
Despite of such progress in this emerging field, it is highly
with good selectivity (Scheme 1A). For instance, Iwasawa et
al.[12l] recently reported Auꢀbased supramolecular catalyst and
Fujita et al.[6e] in 2011, have utilized a Pdꢀbased selfꢀassembled
hollow complex for the antiꢀMarkovnikov selectivity, applicable
only for simple nonꢀsymmetric aryl alkynes. Similarly, the indirect
pathways via hydroamination/acid hydrolysis sequence,
employing Tiꢀcatalysis are also substrate specific.[13] The only
precedent using PtCl2/CO system for a functionalized aryl alkyne
i.e. conjugated enyne was reported by Liu et al.,4c showing antiꢀ
Markovnikov selectivity that was controlled by steric bulk around
the C≡C bond. Alternative to this, new pathways via the
assistance of neighboring group have been discovered to
functionalize nonꢀbenzylic position for the synthesis of further
modifiable carbonyl substrates of high synthetic value. As a
result of this concept, Qi et al. reported a silverꢀcatalyzed
hydration[14] of tertiary propargylic alcohols only that is
anticipated to proceed via in situ generation of carbonate
directing group (Scheme 1B).
desirable to achieve
a highly efficient and regioselective
hydration method for the introduction of C=O bond to
unsymmetrical alkynes of those bearing an aryl ring in one of the
terminus. The solution to this classical unsolved problem is
difficult because of the obvious reactivity of benzylic carbon for
nucleoꢀfunctionalization compared to a nonꢀbenzylic carbon.
This has been clearly illustrated in the context of metalꢀcatalyzed
hydration of various nonterminal aryl alkynes in poor antiꢀ
Markovnikov selectivity.[6a,b,12g] As per our knowledge, very few
examples have been reported to introduce the C=O bond at nonꢀ
benzylic position via hydration of nonꢀsymmetric aryl alkynes
[a]
[b]
Department of Organic Synthesis and Process Chemistry, CSIRꢀ
Indian Institute of Chemical Technology, Hyderabad 500 007,
INDIA.
Eꢀmail: mohaptra@iict.res.in
Homepage: www.iictindia.org
Academy of Scientific and Innovative Research (AcSIR), Mathura
Road, New Delhi 110 025, India
Considering the above limitations and our research
programme on goldꢀcatalyzed hydration and Sahoo’s group,[15]
we postulated that a neighboring carbonyl group participation
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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10.1002/ejoc.201900941
European Journal of Organic Chemistry
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might allow for a antiꢀMarkovnikov hydration of aryl terminated
propargylic carboxylate in a highly regioselective manner. It is of
note from our earlier report that the hydration of propargylic
carboxylate bearing weaker electron withdrawing groups (amide
or alkyl) was either unfruitful or proceeds with a complex
mixture.[16] Although the predominant oxidation at nonꢀbenzylic
carbon is explicable by assuming selective 5ꢀexoꢀdig
cyclization[17] of the acyloxy group over 5ꢀendoꢀdig cyclization
(with subsequent transposition of the oxygen atom), such an
interpretation is inconsistent with common understanding
because the prominent migratory ability of the acyloxy group via
3,3ꢀsigmatropic acyloxy rearrangement for internal alkynes[18]
has also been wellꢀdocumented in various metal catalyzed
rearrangements. This contradiction prompted us to pursue
further research in a new direction in order to figure out the
crucial element governing the unique regioselectivity of this
reaction, which would enable to control the C(2)ꢀregioselective
of a ArꢀC≡C moiety. Realizing the effect of electron withdrawing
group for a selective 5ꢀexoꢀdig cyclization[17hꢀj] and bolstered by
our recent success for a regioselective hydration utilizing a cost
effective and functional group tolerability AuꢀI catalyst,[15b] we
hypothesized that γꢀacetoxy αꢀaryl alkyne could be effectively
hydrated to deliver unique acyloin derivatives. Herein, we detail
our discovery of unprecedented regioselective hydration reaction
which delivered two divergent acyloins using a single cationic
gold catalyst with different stoichiometric amount of water
(Scheme 1C).
With the optimized conditions in hand, the substrate scope
was investigated for different γꢀacetoxy aryl alkynes (1o and 2o,
Table 1. Optimization of reaction conditionsa
O
O2N
Auꢀcat. (2 mol%)
O2N
O
O
Me
O
Agꢀcat. (2 mol%)
H2O (1.5 equiv)
solvent, rt, time
O
Me
2a
1a
time
(h)
2a
entrya
1
Auꢀcat.
Agꢀcat.
AgOTf
solvent
(%)b
1,4ꢀ
dioxane
(CH2)2Cl2
PPh3AuCl
27c
12
2
PPh3AuCl
PPh3AuCl
PPh3AuCl
AgOTf
AgOTf
AgOTf
12
11
3c
4c
CH2Cl2
12
12
traced
traced
THF
1,4ꢀ
dioxane
1,4ꢀ
dioxane
1,4ꢀ
dioxane
1,4ꢀ
dioxane
1,4ꢀ
dioxane
1,4ꢀ
dioxane
1,4ꢀ
dioxane
1,4ꢀ
5
6
(IPr)AuCl
AuCl
AgOTf
AgOTf
ꢀꢀꢀꢀ
12
06
06
06
02
02
01
06
06
17d
22
7
NaAuCl4
AuCl3
trace
<5
8
ꢀꢀꢀꢀ
9e
10
11
12
13
(IPr)AuCl
PPh3AuCl
PPh3AuCl
PPh3AuCl
PPh3AuCl
AgSbF6
AgSbF6
AgNTf2
AgPF6
AgBF4
46
86f
40
Results and Discussion
trace
62
dioxane
1,4ꢀ
dioxane
To test this paradox, we started the optimization study using
model carboxylate, (3ꢀnitrophenyl)propꢀ2ꢀynꢀ1ꢀyl acetate 1a
using our previously developed conditions.[15b] However, it was
found to be inefficient (entry 1, Table 1). It should be noted that
a single regioisomeric hydration product was isolated (27%)
along with the recovery of the starting material 1a. Also, solvents
screening with increased amount of catalyst loadings were
performed, but none of them produced improved results (entries
2ꢀ4, Table 1). The reaction in the presence of carbene based
AuꢀI catalyst afforded 2a in only 17% yield (entry 5, Table 1).
Attempt to use other Au(I) or (III) salts provided inferior results
(entry 6ꢀ8). The reported optimal catalyst ((IPr)AuCl/AgSbF6) as
employed for internal alkyne hydrations by Nolan et al.[12g]
improved the yield slightly (entry 9, Table 1). Considering this
result of counter ion effect, we employed PPh3AuCl as the
catalyst and indeed significant increase in the yield of 2a was
observed (entry 10, Table 1). No yield improvements were
observed when the catalytic system was modified with other
counter ions (AgNTf2, AgPF6 and AgBF4), suggesting a perfect
combination of catalyst and coꢀcatalyst is the key factor to affect
the hydration (entries 11ꢀ13, Table 1). Next, screening of
different solvent system was not beneficial with respect to yield
and duration of the reaction (entries 14ꢀ17). It is noteworthy to
mention here that the reactions produced exclusively single
regioisomeric product in each case.[19]
14
15
16
17
PPh3AuCl
PPh3AuCl
PPh3AuCl
PPh3AuCl
AgSbF6
AgSbF6
AgSbF6
AgSbF6
(CH2)2Cl2 12
24
38
41
18
CH2Cl2
CH3NO2
CH3CN
12
12
12
[a] Unless otherwise mentioned, all reactions were carried out using 0.1 mmol
of 1a using 2 mol% of each Auꢀand Agꢀcatalyst, and 1.5 equiv. of H2O in 0.3 M
solvent without exclusion of air at rt.
[b] Isolated yield.
[c] Reaction was performed using 5 mol% of each of the catalyst.
[d] With recovery of starting material.
[e] Reaction was heated at 80 oC.
[f] The yield was also similar with 1 mol% of each of the catalyst.
Table 2). Primary carboxylates 1aꢀ1g, either bearing electron
withdrawing (for example, –NO2, –F and –CF3, 1aꢀe), neutral (1f)
or donating (1g) substituents on aryl ring all gave the desired
C2ꢀselective hydration products (2aꢀg), while those with electron
neutral or donating substituents proceeded with moderate yields.
Substrates having –OMe, –OAllyl, and –NMe2 substituents on
aryl ring were not worked well, due to the competitive 3,3ꢀ
sigamtropic acyloxy rearrangement due to the electron rich
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10.1002/ejoc.201900941
European Journal of Organic Chemistry
FULL PAPER
Table 2. Scope of the C2ꢀselective hydration for 1o and 2o γꢀacetoxy aryl
alkynesa,b
attached to the carbon bearing the directing group were
hydrated successfully. It is of note that additional acetoxy group
(1p) had no adverse effect on hydration. However, attempt to
hydrate aliphatic alkyne 1s was not successful under the above
optimized conditions.
R
R
PPh3AuCl (1 mol%)
AgSbF6 ( 1 mol%)
OCOCH3
OCOCH3
G
O
2
H2O (1.5 equiv.)
1,4ꢀdoxane (0.3 M)
rt, time, up to 90%
G
R = H, Alkyl, Aryl
During the extension of the reaction scope to tertiary γꢀacetoxy
aryl alkynes, we made a serendipitous discovery of acetate
cleavage. When 1ꢀ(Phenylethynyl)cyclohexyl acetate (3a) was
employed as the substrate, not only the C2ꢀhydration of alkyne
functionality but also deacetylation from the desired product was
observed, i.e. the only acyloin 4a was isolated in 46% yield from
the identical conditions (entry 10, Table 1). The yield of 4a was
improved to 93% by simply increasing the equivalent of water (3
equiv.) without further optimization. This behavior was similar for
other tertiary acetoxy aryl alkynes 3b, 3c, 3e and 3f, which
produced the corresponding hydration products in moderate to
excellent yield. However, neutral aryl alkyne 3d provided 4d in
poor yield (Table 3).
To evaluate the synthetic potential for the current alkyne
hydration, lateꢀstage diversification of complex molecules were
commenced (Table 4A). Remarkably, the hydration of internal
alkyne derived from biomolecular scaffolds such as benzylꢀ
protected carbohydrate (Dꢀglucose) is consistent with previous
results of hydration (as observed in Table 1) to provide the
hydration product 5 without the loss of stereochemistry at
anomeric carbon.[20]
1
R = H, Alkyl, Aryl
R
1 = Ph
17 substrates with rr >99:1
OAc = OCOCH3
OAc
O
OAc
OAc
OAc
Ph
O
O
O
F
CF3
2b, 83%, 2 h
NO2
2c, 87%, 2 h
2d, 79%, 2 h
OAc
F
2a 86%, 2 h
F
OAc
OAc
OAc
O
O
O
O
Me
2g, 46%, 2.5 h
2e, 85%, 1.5 h
NO2
2f, 55%, 2 h
F
2h, 74%, 2 h
OAc
OAc
Ph
OAc
OAc
Ph
Ph
Ph
O
O
O
O
F
2l, 77%, 2.5 h
OAc
NO2
2k, 89%, 2 h
2i, 77%, 2 h
OAc
2j, 62%, 2.5 h
OAc
OTBDPS
OBn
O
O
O
2n, 45%, 2.5 h
2o, 81%, 2.5 h
2m, 90%, 2 h
NO2
OAc
OAc
OAc
OAc OAc
CH3
14
CH3
14
CH3
Ph
4
O
OBnO
2s, 0%, 2 h
O
O
2p, 65%, 2.5 h
2r, 63%, 2 h
2q, 60%, 2 h
On the other hand, hydration of (+)ꢀmenthone derived tertiary
γꢀacetoxy phenyl acetylene 6′ proceeded without deacylation,
furnishing the protected acyloin 6 in 96% yield, probably due to
the unfavorable attack of water to the sterically congested
electrophilic intermediate[21] originated from the methoneꢀring
substituents. Other synthetic applications include bromination of
active benzylic carbon[22a] of 2q and carbonyl chemoselective
reduction[22b] of ketone functionality of 4a to further modifiable
substrates and a chemoselective copperꢀcatalyzed Oꢀ
[a] Unless otherwise noted, reaction was performed with 0.2 mmol of 1, under
the optimized conditions.
[b] Isolated yields.
[c]
The reaction was also attempted at 80 oC for 12 h, after which the
decomposition of the starting material was observed.
nature of C1ꢀcarbon in ArꢀC≡Cꢀunit. Regarding, scope of
secondary γꢀacetoxy aryl alkynes, variation of electron
withdrawing substituents (1h, 1i, 1k and 1m) on either position
of aryl ring, and even aryl group (1i with –F substituent) or
aliphatic groups (neutral (1j, 1l, 1nꢀ1r) or tied with synthetically
relevant protecting groups such as –OBn, –OTBDPS and –OAc)
Table 3. Scope of the deacylative C2ꢀSelective hydration for 3o γꢀacetoxy Aryl
alkynesa,b
Table 4. Synthetic applications (late stage functionalization and synthetic
transformations)a,b,c
[a] All reactions were performed in 0.1 mmol scale.
[b] Isolated yield.
[c] Reagents and conditions: For 2q′, NBS (1.5 equiv.), HBr, CH2Cl2, reflux, 3 h.,
For 4a′, NaBH4, THF–MeOH, 0°Cꢀrt, 30 min. for 4b′, CuI (10 mol%), K3PO4
(0.2 mmol), DMF (0.5 mL), 105 °C, 24 h.
[a] Unless otherwise noted, reaction was performed with 0.2 mmol of 3, under
the optimized conditions.
[b] Isolated yields
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10.1002/ejoc.201900941
European Journal of Organic Chemistry
FULL PAPER
arylation[13b] of acyloin 4b to functionalized benzo[b]furan 4b′ is
demonstrated (Table 4B).
To gain insight into the exact reaction pathway responsible
for the C2ꢀregioselective hydration, we conducted isotope
labelling experiments and controlled experiment (Scheme 2).
Similar observation, 18O incorporation at acetoxy carbonyl rather
than the ketoꢀcarbonyl as confirmed by ESIꢀHRMS (277.1199) of
the acyloin 2l′ without having labelled oxygen (Scheme 2A),
concludes the assisted pathway for current C2ꢀselective
hydration. In order to confirm the unusual behaviour for tertiary
γꢀacetoxy aryl alkynes, i.e. to check whether assisted hydration
and deacetylation (similar to acidꢀcatalyzed deacetylation)
occurs in two independent steps, we conducted Dꢀlabelling
experiment (Scheme 2B, left). If this assumption is correct, we
should see deuterium incorporation (>98%) at benzylic position,
but not in the hydroxyl oxygen. HRMS analysis of the isolated
acyloin confirms the product formed is Dꢀ4a. However, the result
of H2O18 experiment was inconsistent with a scenario that a
single 18O labelled acyloin 18Oꢀ4a (ESIꢀHRMS = 243.1242) was
formed, which is presumably formed via a different hydrolysis
pathway. One could also imagine a hydration product (with 18O
in carbonyl oxygen) with similar isotopic mass via a nonꢀassisted
Scheme 3: A Plausible mechanism for the assisted hydration of 3oꢀγꢀacetoxy
aryl alkynea
[a] The isotopic water (D2O18) used in this scheme is for better understanding of
the mechanism, though isotopic experiments using D2O and H2O18 were
carried out independently.
(A) Isotopic labeling experiment for probing the source of carbonyl oxygen
water during the analysis. This concern was further corroborated
by 18H2O experiment (Scheme 2B, right), which afforded a single
18Oꢀincorporated acyloin.[23] One more alternative pathway
proposed via allene dihydroxylation,[24] which could be
eliminated as the desired acyloin 4a but it was not formed by
subjecting allene 3a′ to the standard reaction conditions
(Scheme 2C).
Me
O18
Ph
Me
OH
Standard
O
2
O
2
O
K2CO3 (3 equiv.)
MeOH:H2O (9:1)
conditions
Ph
Ph
Ph
Ph
2
H2O18 (5 equiv.)
Ph
O
O
2l', HRMS (ESI)
= 277.1199
1l
18Oꢀ2l, HRMS (ESI)
= 299.1528
(B) Isotopic labeling experiment for probing the source of hydroxyl oxygen
(for 3o substrates)
Given the previous literature precedence of 1,2ꢀacyloxy
migration enabled hydration[15,17i,j] and the above experimental
observations, we depicted a plausible mechanism as shown in
Scheme 3 (the mechanism for 2o γꢀactoxy aryl alkyne is shown
in Supporting Inforamtion). The Au(I)ꢀcoordinated alkyne A
undergoes 5ꢀexoꢀdig attack of the carbonyl oxygen to the C2ꢀ
carbon of aryl alkyne to generate a fiveꢀmembered electrophilic
species B, which can further react with water to afford an
intermediate C. Following two independent steps of 1,3ꢀproton
transfer and normal acetate hydrolysis, C can give rise to the
final hydration product by regenerating the AuꢀI catalyst via proto
deuteration as the final step (path a, Scheme 3). However,
considering the experimental results, we proposed that the
intermediate C undergoes a concerted deacetylationꢀproton
transfer process to provide a carbocationic intermediate D.
Finally, nucleophilic attack of water to D produces acyloin after
proto deuteration of E completing the catalytic cycle (path b,
Scheme 3).
Me
Standard
Standard
OH
18OH
D D
Ph
O
O
conditions
conditions
Ph
D2O (10 equiv)
O
H2O18 (10 equiv.)
O
Ph
18Oꢀ4a, HRMS (ESI)
= 243.1242
3a
Dꢀ4a, HRMS (ESI) = 243.1330
H = exchangable proton
(C) Control experiment for eliminating the dihydrohydroxylation (of allene)
pathway
Standard
conditions
OH
Ph
H
excess Et3N
Ph
(Not observed)
3a
•
(Dihydroxylation)
O
Allene
Decomposed
after 1 h
Scheme 2. Experimental evidences for mechanistic pathwaya
[a] See experimental section for the details of experimental procedure.
hydration followed by a normal esterꢀhydrolysis pathway. To
differentiate between these two pathways, the hydration of 3o γꢀ
hydroxy aryl alkyne 3a′ was attempted under the standard
conditions. Not surprisingly, we did not observe desired the
hydration product 4a, thus confirming an assisted reaction
pathway. No incorporation of deuterium in hydroxyl oxygen of Dꢀ
4a is probably because of rapid Hꢀexchange by adventitious
Conclusions
In summary, we have developed an efficient and robust
protocol for highly regioselective hydration of various γꢀacetoxy
aryl alkynes in an antiꢀMarkovnikov fashion, leading to two
different acyloins with similar nonꢀbenzylic hydration selectivity
under identical conditions in good to excellent yields. Our
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10.1002/ejoc.201900941
European Journal of Organic Chemistry
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anhydrous Na2SO4 and concentrated under reduced pressure to get the
crude phenyl propargyl alcohol derivatives.
reaction operates at room temperature with broad functional
group compatibility, could also be applied for the modification of
complex natural products and some valuable postꢀ
functionalization of the synthesized acyloins. Furthermore,
isotopic labeling studies have revealed that the regioselectivity
of hydration is a result of the assistance of a neighboring
carbonyl group. A suitable pathway for the unexpected result,
obtained from 3o γꢀacetoxy aryl alkynes, has also been proposed
based on isotopic and controlled experimental results.
(c) General procedure for acetylation of phenyl propargyl alcohol
(Pꢀ3): To a solution of the crude phenyl propargyl alcohol (1.0 mmol) in
anhydrous CH2Cl2 (10 mL) triethylamine (1.5 mmol), acetic anhydride
(2.0 mmol), was added drop wise, followed by the addition of catalytic
DMAP at 0 °C into reaction mixture under the nitrogen atmosphere at
0 °C. The resultant mixture was stirred at room temperature to complete
consumption of starting material (indicated by TLC). Then the reaction
mixture was washed with brine solution (15 mL), dried over Na2SO4 and
the solvent was removed under reduced pressure. Obtained crude oil
was purified by silica gel column chromatography to obtain the acetylated
hydration precursor (up to 96% yield).
Experimental Section
General Information: All reactions were carried out under ambient
atmosphere, unless otherwise stated. All starting materials and reagents
were obtained from commercial producers and are used without further
purification. Solvents were generally used as supplied by the
manufacturer except THF (THF was freshly distilled over sodium and
benzophenone under inert atmosphere). Column chromatography was
carried out by using silica gel (100–200 mesh) unless otherwise
mentioned. Analytical thin layer chromatography (TLC) was run on Merck
silica gel 60 F254 precoated plates (250 ꢁm thickness). Infrared spectra
were recorded in CHCl3/neat (as mentioned) and reported in wave
number (cm−1). Mass spectral data were obtained using MS (EI, ESI and
APCI) HRMS mass spectrometers. HPLC was performed on JASCO
HPLC systems consisting of the following; detector, 875ꢀUV or UVꢀ970,
measured at 210 nm and 254 nm; column, ATLANTIS C18 (4.6 × 150
mm, 5u) and LUX AMISOSE (4.6 × 250 mm, 5u); mobile phase,
acetonitrile, water, isopropanol and hexane; flow rate, 1 mL/min. 1H NMR
spectra were recorded at 300, 400, 500 and 13C NMR spectra 75, 100,
125 MHz in CDCl3 solution, chemical shifts are in ppm downfield from
tetramethylsilane and coupling constants (J) are reported in hertz (Hz).
The following abbreviations are used to designate signal multiplicity: s =
singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad.
II Experimental procedure and analytical data for hydration
precursors
3ꢀ(3ꢀNitrophenyl)propꢀ2ꢀynꢀ1ꢀyl acetate (1a): Following the general
procedure Pꢀ1 and Pꢀ3, 1a (980 mg, 71% yield) was obtained as a
colorless liquid starting from 1ꢀethynylꢀ3ꢀnitrobenzene. Rf 0.35 (9:1
hexane/EtOAc); IR (neat) νmax 3084, 2928, 1746, 1531, 1477, 1377, 1352,
1223, 1033, 964, 809, 736, 674 cm–1; 1H NMR (400 MHz, CDCl3) δ 8.30
(t, J = 1.9 Hz, 1H), 8.19 (ddd, J = 8.3, 2.2, 1.1 Hz, 1H), 7.75 (td, J = 7.7,
1.2 Hz, 1H), 7.51 (t, J = 7.9 Hz, 1H), 4.92 (s, 2H), 2.15 (s, 3H) ppm; 13C
NMR (100 MHz, CDCl3) δ 170.2, 148.0, 137.5, 129.4, 126.7, 123.9,
123.5, 85.7, 83.9, 52.3, 20.7 ppm; HRMS (APCI) m/z: [M ꢀ H]+ calcd for
C11H8O4N 218.0447; found: 218.0433.
3ꢀ(3ꢀFluorophenyl)propꢀ2ꢀynꢀ1ꢀyl acetate (1b): Following the general
procedure Pꢀ1 and Pꢀ3, 1b (120 mg, 69% yield) was obtained as a
colorless liquid starting from 1ꢀethynylꢀ3ꢀfluorobenzene. Rf 0.52 (19:1
hexane/EtOAc); (IR (neat) νmax 2928, 2855, 1747, 1578, 1482, 1434,
1
1370, 1225, 1031, 872, 785, 682 cm–1; H NMR (500 MHz, CDCl3) δ
7.30–7.27 (m, 1H), 7.25–7.21 (m, 1H), 7.15 (ddd, J = 9.3, 5.2, 1.4 Hz,
1H), 7.04 (tdd, J = 8.5, 2.6, 1.2 Hz, 1H), 4.89 (s, 2H), 2.13 (s, 3H) ppm;
13C NMR (100 MHz, CDCl3) δ 170.2, 163.5, 161.0, 129.9, 129.8, 127.7,
127.7, 124.0, 123.9, 118.8, 118.5, 116.2, 116.0, 85.1, 85.1, 83.9, 52.6,
20.7 ppm; 19F NMR (375 MHz, CDCl3) δ ꢀ112.5 ppm; HRMS (APCI) m/z:
[M + H]+ calcd for C11H10FO2 193.0659; found: 193.0664.
(a) General procedure for formylation of phenyl acetylene (Pꢀ1): To a
solution of phenyl acetylene (1.0 mmol) in THF (3 mL), LHMDS (1.0 mL,
1 M in toluene, 1.0 mmol) was added dropwise using a syringe at −78 °C
under nitrogen atmosphere and stirred at this temperature for 45 min.
Then paraformaldehyde solution in THF (1 mL, 2.0 mmol) was added
dropwise to this ylide solution. Reaction mixture was slowly warmed to
room temperature and continued to stir until completion of the reaction
(indicated by TLC). The reaction was quenched with saturated aqueous
NH4Cl solution (2 mL) and diluted with ethyl acetate (10 mL). The organic
layer was separated and the aqueous layer extracted with ethyl acetate
(3 × 10 mL). The combined organic layer was washed with brine (15 mL),
dried over anhydrous Na2SO4 and concentrated under reduced pressure
to get the crude phenyl propargyl alcohol.
3ꢀ(4ꢀFluorophenyl)propꢀ2ꢀynꢀ1ꢀyl acetate (1c): Following the general
procedure Pꢀ1 and Pꢀ3, 1c (110 mg, 76% yield) was obtained as a
colorless liquid starting from 1ꢀethynylꢀ4ꢀfluorobenzene. Rf 0.50 (19:1
hexane/EtOAc); IR (neat) νmax 2922, 2851, 1742, 1691, 1634, 1583,
1472, 1387, 1209, 1082, 870 cm–1; 1H NMR (500 MHz, CDCl3) δ 7.44 (dd,
J = 8.8, 5.4 Hz, 2H), 7.01 (t, J = 8.7 Hz, 2H), 4.89 (s, 2H), 2.13 (s, 3H)
ppm; 13C NMR (100 MHz, CDCl3) δ 170.3, 164.0, 161.5, 133.9, 133.8,
118.2, 115.7, 115.5, 85.4, 82.7, 52.7, 20.7 ppm; HRMS (APCI) m/z: [M +
H]+ calcd for C11H9FO2 193.0659; found: 193.0665.
(b) General procedure for synthesis of secondary or tertiary phenyl
propargyl alcohol (Pꢀ2): To a solution of phenyl acetylene (1.0 mmol) in
THF, LiHMDS (1.0 mL, 1 M in toluene, 1.0 mmol) was added dropwise at
−78 °C under nitrogen atmosphere and stirred at this temperature for 30
min. Then aldehyde/ketone solution in THF (1.5 mL, 1.0 mmol) was
added dropwise to this ylide solution. Reaction mixture was slowly
warmed to room temperature and continued to stir till the completion of
reaction (monitored by TLC). After the consumption of starting material,
reaction mixture was quenched with saturated aqueous NH4Cl solution (2
mL) and diluted with ethyl acetate (10 mL). The organic layer was
separated and the aqueous layer extracted with ethyl acetate (2 × 10 mL).
The combined organic layers were washed with brine (15 mL), dried over
3ꢀ(2ꢀ(Trifluoromethyl)phenyl)propꢀ2ꢀynyl acetate (1d): Following the
general procedure Pꢀ1 and Pꢀ3, 1d (90 mg, 71% yield) was obtained as a
pale
yellow
colour
liquid
starting
from
1ꢀethynylꢀ2ꢀ
(trifluoromethyl)benzene. Rf 0.45 (9:1 hexane/EtOAc); IR (neat) νmax
3078, 2945, 2246, 1746, 1574, 1492, 1451, 1360, 1317, 1218, 1128,
1031, 957, 765, 650 cm–1; 1H NMR (500 MHz, CDCl3) δ 7.65 (d, J = 7.8
Hz, 1H), 7.60 (d, J = 7.7 Hz, 1H), 7.49 (t, J = 7.6 Hz, 1H), 7.42 (t, J = 7.7
Hz, 1H), 4.93 (s, 2H), 2.13 (s, 3H) ppm; 13C NMR (125 MHz, CDCl3) δ
170.2, 134.2, 132.2, 132.0, 131.7, 131.4, 128.5, 126.6, 125.8, 125.8,
124.4, 122.3, 120.4, 120.1, 88.6, 82.2, 52.5, 20.7 ppm; 19F NMR (376
MHz, CDCl3) δ −62.3 ppm; HRMS (ESI) m/z: [M + Na]+ calcd for
C12H9F3O2Na: 265.0452; found: 265.0454.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900941
European Journal of Organic Chemistry
FULL PAPER
3ꢀ(3,5ꢀDifluorophenyl)propꢀ2ꢀynꢀ1ꢀyl acetate (1e): Following the
general procedure Pꢀ1 and Pꢀ3, 1e (136 mg, 74% yield) was obtained as
a pale yellow colour liquid starting from 1ꢀethynylꢀ3,5ꢀdifluorobenzene. Rf
0.55 (9:1 hexane/EtOAc); IR (neat) νmax 3087, 2937, 1750, 1617, 1587,
1431, 1379, 1337, 1224, 1123, 1048, 990, 859, 672 cm–1; 1H NMR (500
MHz, CDCl3) δ 7.00–6.93 (m, 2H), 6.81 (tt, J = 8.9, 2.3 Hz, 1H), 4.88 (s,
2H), 2.14 (s, 3H) ppm; 13C NMR (125 MHz, CDCl3) δ 170.1, 163.6, 163.5,
161.6, 161.5, 124.8, 114.9, 114.9, 114.8, 114.7, 105.2, 105.0, 104.8,
85.0, 84.0, 52.3, 20.7 ppm; 19F NMR (376 MHz, CDCl3) δ −109.5 ppm;
HRMS (APCI) m/z: [M ꢀ H]+ calcd for C11H7F2O2: 209.0408; found:
209.0394.
4ꢀ(3ꢀNitrophenyl)ꢀ1ꢀphenylbutꢀ3ꢀynꢀ2ꢀyl acetate (1k): Following the
general procedure Pꢀ2 and Pꢀ3, 1k (163 mg, 64% yield) (mp–82) was
obtained as a light yellow color solid starting from 2ꢀphenyl acetaldehyde.
Rf 0.36 (9:1 hexane/EtOAc); IR (neat) νmax 2960, 2861, 2229, 1736, 1530,
1493, 1349, 1231, 1023, 889, 739, 668 cm–1; 1H NMR (500 MHz, CDCl3)
δ 8.22 (t, J = 1.8 Hz, 1H), 8.16 (ddd, J = 8.2, 2.3, 0.9 Hz, 1H), 7.66 (td, J
= 7.6, 1.2 Hz, 1H), 7.48 (t, J = 7.9 Hz, 1H), 7.37–7.27 (m, 5H), 5.77 (t, J =
6.8 Hz, 1H), 3.18 (qd, J = 13.6, 6.8 Hz, 2H), 2.10 (s, 3H) ppm; 13C NMR
(125 MHz, CDCl3) δ 169.8, 148.0, 137.4, 135.6, 129.7, 129.3, 128.4,
127.2, 126.7, 124.0, 123.4, 88.8, 83.7, 64.7, 41.0, 20.9 ppm; HRMS (ESI)
m/z: [M + Na]+ calcd for C18H15NO4Na 332.0893; found: 332.0891.
3ꢀPhenylpropꢀ2ꢀynꢀ1ꢀyl acetate (1f): Following the general procedure
Pꢀ1 and Pꢀ3, 1f (201 mg, 79% yield) was obtained as a colorless liquid
starting from ethynylbenzene. Rf 0.48 (9:1 hexane/EtOAc); IR (neat) νmax
1,5ꢀDiphenylpentꢀ1ꢀynꢀ3ꢀyl acetate (1l): Following the general
procedure Pꢀ2 and Pꢀ3, 1l (520 mg, 72% yield) was obtained as a
colorless liquid starting from 3ꢀphenylpropanal. Rf 0.47 (9:1
hexane/EtOAc); IR (neat) νmax 3062, 2938, 2227, 1749, 1602, 1496,
1448, 1221, 1021, 757, 695 cm−1; 1H NMR (400MHz, CDCl3) δ 7.48–7.43
3062, 2938, 2227, 1744, 1600, 1491, 1446, 1226, 1030, 758, 692 cm−1
;
1H NMR (400 MHz, CDCl3) δ 7.54–7.42 (m, 2H), 7.39–7.27 (m, 3H),
4.90 (s, 2H), 2.12 (s, 3H)ppm 13C NMR (100 MHz, CDCl3) δ 170.2, 131.8, (m, 2H), 7.34–7.27 (m, 5H), 7.24–7.18 (m, 3H), 5.61 (t, J= 6.480 Hz, 1H),
128.7, 128.2, 122.1, 86.4, 82.9, 52.7, 20.7 ppm; HRMS (APCI) m/z: [M +
2.84 (t, J=7.947Hz, 2H), 2.19 (ddd, J = 12.5, 7.4, 4.3 Hz, 2H), 2.10 (s,
3H) ppm; 13C NMR (125 MHz, CDCl3) δ 170.0, 140.8, 131.9, 128.6, 128.5,
128.4, 128.2, 126.1, 122.2, 86.2, 85.7, 64.0, 36.4, 31.4, 21.0 ppm; HRMS
(ESI) m/z: [M + H]+ calcd for C19H19O2 279.1380; found: 279.1400.
H]+ 175.0753; found: 175.0748.
3ꢀ(pꢀTolyl)propꢀ2ꢀynꢀ1ꢀyl acetate (1g): Following the general procedure
Pꢀ1 and Pꢀ3, 1g (105 mg, 70% yield) was obtained as a colorless liquid
starting from 1ꢀethynylꢀ4ꢀmethylbenzene. Rf 0.54 (19:1 hexane/EtOAc);
IR (neat) νmax 2931, 2859, 1740, 1634, 1585, 1471, 1386, 1219, 1020
cm–1; 1H NMR (500 MHz, CDCl3) δ 7.35 (d, J = 8.1 Hz, 2H), 7.11 (d, J =
8.1 Hz, 2H), 4.90 (s, 2H), 2.34 (s, 3H), 2.13 (s, 3H) ppm; 13C NMR (100
MHz, CDCl3) δ 170.4, 138.9, 131.7, 129.0, 118.9, 86.6, 82.1, 52.9, 21.4,
20.8 ppm; HRMS (APCI) m/z: [M + H]+ calcd for C12H13O2 189.0910;
found: 189.0912.
1ꢀ(3ꢀNitrophenyl)ꢀ5ꢀphenylpentꢀ1ꢀynꢀ3ꢀyl acetate (1m): Following the
general procedure Pꢀ2 and Pꢀ3, 1m (110 mg, 62% yield) was obtained as
a
colorless liquid starting from 3ꢀphenylpropanal. Rf 0.44 (9:1
hexane/EtOAc); IR (neat) νmax 2926, 2858, 2234, 1743, 1531, 1351, 1227,
1026, 740 cm–1; 1H NMR (400 MHz, CDCl3) δ 8.28 (t, J = 1.8 Hz, 1H),
8.18 (ddd, J = 8.3, 2.2, 0.9 Hz, 1H), 7.74 (td, J = 7.7, 1.2 Hz, 1H), 7.50 (t,
J = 8.1 Hz, 1H), 7.33–7.28 (m, 2H), 7.24–7.20 (m, 3H), 5.58 (t, J = 6.6
Hz, 1H), 2.85 (t, J = 7.7 Hz, 2H), 2.28–2.16 (m, 2H), 2.12 (s, 3H) ppm;
13C NMR (125 MHz, CDCl3) δ 169.9, 148.0, 140.4, 137.5, 129.3, 128.6,
128.4, 126.7, 126.3, 124.0, 123.4, 89.0, 83.1, 63.6, 36.1, 31.3, 20.9 ppm;
HRMS (ESI) m/z: [M + Na]+ calcd for C19H17NO4Na 346.1050; found:
346.1029.
1ꢀ(3ꢀNitrophenyl)ꢀ3ꢀphenylpropꢀ2ꢀynꢀ1ꢀyl acetate (1h): Following the
general procedure Pꢀ2 and Pꢀ3, 1h (142 mg, 59% yield) was obtained as
a brown colored liquid starting from 3ꢀnitro benzaldehyde; Rf 0.48 (9:1
hexane/EtOAc); IR (neat) νmax 2926, 2330, 1748, 1531, 1476, 1374, 1346,
1
1220, 1030, 963, 819, 670 cm–1; H NMR (400 MHz, CDCl3) δ 8.48 (t, J =
1.9 Hz, 1H), 8.24 (ddd, J = 8.2, 2.3, 1.0 Hz, 1H), 7.92 (d, J = 7.7 Hz, 1H),
7.60 (t, J = 8.0 Hz, 1H), 7.49 (m, 2H), 7.38–7.30 (m, 3H), 6.76 (s, 1H),
2.18 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 169.6, 148.4, 139.3,
133.7, 132.0, 129.7, 129.2, 128.4, 123.8, 122.7, 121.4, 88.1, 84.2, 64.9,
21.0 ppm; HRMS (APCI) m/z: [M ꢀ H]+ calcd for C17H12O4N 294.0760;
found: 294.0763.
5ꢀ(Benzyloxy)ꢀ1ꢀphenylpentꢀ1ꢀynꢀ3ꢀyl acetate (1n): Following the
general procedure Pꢀ2 and Pꢀ3, 1n (163 mg, 63% yield) was obtained as
a colorless liquid starting from 3ꢀ(benzyloxy)propanal. Rf 0.43 (9:1
hexane/EtOAc); IR (neat) νmax 2933, 2866, 2865, 2232, 1742, 1599, 1490,
1447, 1370, 1230, 1097, 1021, 755, 695 cm–1; 1H NMR (400 MHz,
CDCl3) δ 7.46–7.39 (m, 2H), 7.36–7.25 (m, 8H), 5.79 (t, J = 6.8 Hz, 1H),
4.56–4.48 (m, 2H), 3.72–3.59 (m, 2H), 2.26–2.09 (m, 2H), 2.07 (s, 3H).
ppm; 13C NMR (125 MHz, CDCl3) δ 169.9, 138.1, 131.8, 128.6, 128.3,
128.2, 127.7, 127.6, 122.2, 86.2, 85.4, 73.0, 65.8, 62.0, 35.1, 21.0 ppm;
HRMS (ESI) m/z: [M + Na]+ calcd for C20H20O3Na 331.1305; found:
331.1300.
1ꢀ(4ꢀFluorophenyl)ꢀ3ꢀphenylpropꢀ2ꢀynꢀ1ꢀyl acetate (1i): Following the
general procedure Pꢀ2 and Pꢀ3, 1i (107 mg, 56% yield) was obtained as
a pale yellow colored liquid starting from 4ꢀflouro benzaldehyde. Rf 0.60
(24:1 hexane/EtOAc); IR (neat) νmax 3058, 2932, 2230, 1744, 1604, 1510,
1493, 1370, 1222, 1040, 950, 835, 757, 691 cm−1; 1H NMR (500 MHz,
CDCl3) δ 7.58 (dd, J = 8.7, 5.3 Hz, 2H), 7.48 (dd, J = 7.8, 1.7 Hz, 2H),
7.36–7.29 (m, 3H), 7.08 (t, J = 8.7 Hz, 2H), 6.67 (s, 1H), 2.12 (s, 3H)
ppm; 13C NMR (100 MHz, CDCl3) δ 169.8, 164,2, 161.7, 133.1, 133.1,
131.9, 129.8, 129.7, 128.9, 128.3, 121.9, 115.7, 115.5, 87.2, 85.3, 65.4,
21.1 ppm; 19F NMR (376 MHz, CDCl3) δ −112.5 ppm; HRMS (ESI) m/z:
[M + Na]+ calcd for C17H13FNaO2 [M + Na]+ 291.0792; found: 291.0794.
5ꢀ((tertꢀButyldiphenylsilyl)oxy)ꢀ1ꢀphenylpentꢀ1ꢀynꢀ3ꢀyl acetate (1o):
Following the general procedure Pꢀ2 and Pꢀ3, 1o (196 mg, 72% yield)
was obtained as
a
colorless liquid starting from 3ꢀ((tertꢀ
butyldiphenylsilyl)oxy)propanal; Rf 0.48 (9:1 hexane/EtOAc); IR (neat)
νmax 2933, 2859, 2231, 1745, 1468, 1431, 1369, 1230, 1108, 1018, 701
cm–1; 1H NMR (500 MHz, CDCl3) δ 7.69–7.65 (m, 4H), 7.42–7.26 (m,
11H), 5.87 (t, J = 6.9 Hz, 1H), 3.88 (m, 1H), 3.81 (m, 1H), 2.16 (m, 1H),
2.10 (m, 1H), 2.06 (s, 3H), 1.06 (s, 9H) ppm; 13C NMR (125 MHz,
CDCl3) δ 169.8, 135.5, 133.5, 131.9, 129.6, 128.5, 128.1, 127.6, 122.2,
86.4, 85.4, 61.8, 59.6, 37.7, 26.8, 19.1, 14.2 ppm; HRMS (ESI) m/z: [M +
Na]+ calcd for C29H32O3SiNa 479.2013; found: 479.2029.
1,4ꢀDiphenylbutꢀ3ꢀynꢀ2ꢀyl acetate (1j): Following the general procedure
Pꢀ2 and Pꢀ3, 1j (149 mg, 68% yield) was obtained as a colorless liquid
starting from 2ꢀphenyl acetaldehyde. Rf 0.39 (9:1 hexane/EtOAc); IR
(neat) νmax 2930, 2235, 1743, 1600, 1492, 1448, 1370, 1228, 1020, 756,
695 cm–1; 1H NMR (400 MHz, CDCl3) δ 7.40–7.36 (m, 2H), 7.32–7.23 (m,
8H), 5.79 (m, 1H), 3.14 (dd, J = 6.6, 1.9 Hz, 2H), 2.03 (s, 3H) ppm; 13C
NMR (100 MHz, CDCl3) δ 169.8, 135.9, 131.8, 129.7, 128.6, 128.3,
128.2 127.0, 122.1, 86.2, 86.0, 65.0, 41.3, 21.0 ppm; HRMS (ESI) m/z:
[M + Na]+ calcd for C18H16O2Na 287.1043; found: 287.1049.
1,7ꢀDiphenylheptꢀ1ꢀyneꢀ3,5ꢀdiyldiacetate (1p): Following the general
procedure Pꢀ2 and Pꢀ3, 1p (110 mg, 89% yield) was obtained as a
colorless liquid starting from 3ꢀ((tertꢀbutyldimethylsilyl)oxy)ꢀ5ꢀ
phenylpentanal. Rf 0.52 (9:1 hexane/EtOAc); IR (neat) νmax 2929, 2236,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900941
European Journal of Organic Chemistry
FULL PAPER
1741, 1601, 1492, 1446, 1371, 1231, 1022, 757, 696 cm−1; 1H NMR (400
MHz, CDCl3) δ 7.44–7.40 (m, 2H), 7.33–7.25 (m, 5H), 7.19–7.14 (m, 3H),
5,67 (dd, J = 8.0, 6.0, 1H), 5.22 (m, 1H), 2.70–2.63 (m, 2H), 2.23 (m, 1H),
2.13 (m, 1H), 2.09 (s,3H) 2.03 (s, 3H), 2.02ꢀ1.91 (m, 2H) ppm; 13C NMR
(100 MHz) δ 170.4, 169.7, 141.1, 131.8, 128.6, 128.4, 128.2, 128.2,
125.9, 121.9, 86.0, 85.4, 70.5, 61.8, 38.9, 35.9, 31.4, 21.1, 21.0 ppm;
HRMS (ESI) m/z: [M + H]+ calcd for C23H25O4 : 365.1747; found:
365.1733.
2,4ꢀDiphenylbutꢀ3ꢀynꢀ2ꢀyl acetate (3d): Following the general
procedure Pꢀ2 and Pꢀ3, 3d (122 mg, 53% yield) was obtained as a pale
yellow color liquid starting from acetophenone. Rf
hexane/EtOAc); IR (neat) νmax 2927, 2854, 1740, 1638, 1600, 1499, 1445,
1076, 1020, 745, 691 cm−1 1H NMR (300 MHz, CDCl3) δ 7.67–7.61 (m,
0.57 (19:1
;
2H), 7.55–7.48 (m, 2H), 7.42–7.25 (m, 6H) 2.09 (s, 3H), 1.97 (s, 3H); 13C
NMR (100 MHz, CDCl3), δ 168.5, 142.7, 131.9, 128.5, 128.3, 128.2,
127.8, 124.9, 122.5, 88.5, 87.1, 76.0, 32.1, 21.8 ppm; HRMS (ESI) m/z:
[M + Na]+ calcd for C18H16O2Na 287.1043; found: 287.1049.
1ꢀPhenyloctꢀ1ꢀynꢀ3ꢀyl acetate (1q): Following the general procedure Pꢀ
1 and Pꢀ4, 1q (464 mg, 65% yield) was obtained as a colorless liquid
starting from 1ꢀhexanal. Rf 0.65 (19:1 hexane/EtOAc); IR (neat) νmax 2930,
2863, 2233,1747, 1491, 1443, 1371, 1227, 1020, 757, 691 cm–1; 1H NMR
(500 MHz, CDCl3) δ 7.47–7.42 (m, 2H), 7.33–7.27 (m, 3H), 5.60 (t, J =
6.7 Hz, 1H), 2.11 (s, 3H), 1.85 (m, 2H), 1.54–1.47 (m, 2H), 1.34 (m, 4H),
0.91 (t, J = 7.1 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 169.5, 131.5,
128.2, 128.0, 122.1, 86.5, 84.9, 64.2, 34.6, 31.0, 24.5, 22.2, 20.7, 13.7
ppm; HRMS (ESI) m/z: [M + Na]+ calcd for C16H20O2Na 267.1356; found:
267.1366.
2ꢀ(4ꢀchlorophenyl)ꢀ4ꢀ(4ꢀ(trifluoromethyl)phenyl)butꢀ3ꢀynꢀ2ꢀyl acetate
(3e): Following the general procedure Pꢀ2 and Pꢀ3, 3e (110 mg, 71%
yield) (mp – 84 oC) was obtained as a light yellow color solid starting from
1ꢀ(4ꢀchlorophenyl)ethanone. Rf 0.55 (19:1 hexane/EtOAc); IR (neat) νmax
3058, 2937, 2857, 2228, 2082, 1749, 1619, 1490, 1324, 1227, 1169,
1065, 837 cm−1 1H NMR (400 MHz, CDCl3) δ 7.63–7.58 (m, 4H), 7.57–
;
7.56 (m, 2H), 7.34 (dd, J = 6.6, 2.1 Hz, 2H), 2.09 (s, 3H), 1.96 (s, 3H)
ppm; 13C NMR (125 MHz, CDCl3) δ 168.5, 140.9, 133.8, 132.1, 130.6,
130.3, 128.6, 126.4, 126.0, 125.2, 125.2, 90.4, 86.0, 75.2, 31.7, 21.6
ppm; 19F NMR (375 MHz, CDCl3)
δ −62.9 ppm; Anal. calcd for
C19H14ClF3O2: C, 62.22; H, 3.84; found: C, 62.30; H, 4.00.
1ꢀPhenyloctadecꢀ1ꢀynꢀ3ꢀyl acetate (1r): Following the general
procedure Pꢀ2 and Pꢀ3, 1r (112 mg, 66% yield) was obtained as a
colorless liquid starting from 1ꢀhexadecanal; Rf 0.55 (49:1
hexane/EtOAc); IR (neat) νmax 3215, 2922, 2851, 1691, 1634, 1583, 1472,
1387, 1209, 1082 cm–1; 1H NMR (500 MHz, CDCl3) δ 7.46–7.41 (m, 2H),
7.33–7.26 (m, 3H), 5.59 (t, J = 6.7 Hz, 1H), 2.11 (s, 3H), 1.88–1.81 (m,
2H), 1.53–1.45 (m, 2H), 1.38–1.23 (m, 26H), 0.88 (t, J = 7.1 Hz, 3H)
ppm; 13C NMR (100 MHz, CDCl3) δ 170.0, 131.9, 128.5, 128.2, 122.4,
86.7, 85.2, 64.6, 34.9, 31.9, 29.7, 29.5, 29.5, 29.4, 29.2, 25.1, 22.7, 21.1,
14.1 ppm; HRMS (ESI) m/z: [M + Na]+ calcd for C26H40O2Na 407.2921;
found: 407.2911.
2ꢀ(4ꢀNitrophenyl)ꢀ4ꢀphenylbutꢀ3ꢀynꢀ2ꢀyl acetate (3f): Following the
general procedure Pꢀ2 and Pꢀ3, 3f (101 mg, 72% yield) (mp – 115 oC)
was obtained as
a
yellow color solid starting from 1ꢀ(4ꢀ
nitrophenyl)ethanone; Rf 0.49 (19:1 hexane/EtOAc); IR (neat) νmax 2926,
2862, 2223, 2115, 1750, 1620, 1489, 1334, 1225, 1139, 1050, 831 cm−1;
1H NMR (500 MHz, CDCl3) δ 8.23 (d, J = 9.0 Hz, 2H), 7.80 (d, J = 9.0 Hz,
2H), 7.52 (m, 2H), 7.39–7.31 (m, 3H), 2.12 (s, 3H), 1.97 (s, 3H) ppm; 13C
NMR (125 MHz, CDCl3) δ 168.4, 149.9, 147.4, 131.9, 129.0, 128.3,
126.0, 123.7, 121.8, 88.0, 87.1, 75.2, 32.0, 21.6 ppm; Anal. calcd for
C18H15O4N C, 69.89; H, 4.89; N, 4.53; found: C, 69.41; H, 4.84; N, 4.41.
1ꢀ(Phenylethynyl)cyclohexyl acetate (3a): Following the general
procedure Pꢀ2 and Pꢀ3, 3a (970 mg, 76% yield) was obtained as a
4ꢀ(4ꢀ(Trifluoromethyl)phenyl)ꢀ1ꢀ((2R,3S,4R,5R,6R)ꢀ3,4,5ꢀ
colorless liquid starting from cyclohexanone. Rf
0.41 (9:1
tris(benzyloxy)ꢀ6ꢀ((benzyloxy) methyl)tetrahydroꢀ2Hꢀpyranꢀ2ꢀyl)butꢀ
3ꢀynꢀ2ꢀyl acetate (5ʹ): Following the general procedure Pꢀ2 and Pꢀ3, 5ʹ
(240 mg, 87% yield) was obtained as a white solid starting from 2ꢀ
((2R,3S,4R,5R,6R)ꢀ3,4,5ꢀtris(benzyloxy)ꢀ6ꢀ((benzyloxy)methyl)
tetrahydroꢀ2Hꢀpyranꢀ2ꢀyl)acetaldehyde (200 mg, 0.35 mmol), Mp. 72ꢀ73
oC; Rf 0.42 (17:1 hexane/EtOAc); 1H NMR (400 MHz, CDCl3) δ 7.54 (d, J
= 8.3 Hz, 2H ), 7.51 (d, J = 8.3 Hz, 2H), 7.35–7.21 (m, 18H), 7.14–7.10
(m, 2H), 5.74 (dd, J = 10.0, 4.8 Hz, 1H), 4.91 (d, J = 10.8 Hz, 1H), 4. 80
(dd, J = 10.8, 2.4 Hz, 2H), 4.71 (d, J = 11.7 Hz, 1H), 4.63 (dd, J = 11.9,
6.7 Hz, 2H), 4.46 (dd, J = 11.4, 5.2 Hz, 2H), 4.39 (m, 1H), 3.80–3.64 (m,
6H), 2.33 (m, 1H), 2.22 (m, 1H), 2.09 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3) δ 169.7, 138.6, 138.2, 138.0, 137.9, 132.1, 128.4, 128.4, 128.4,
128.0, 127.9, 127.8, 127.7, 127.7, 125.9, 125.2, 125.2, 88.3, 84.7, 82.5,
79.2, 77.6, 75.5, 75.1, 73.5, 73.2, 71.6, 71.2, 68.6, 62.4, 30.4, 21.0 ppm;
HRMS (ESI) m/z: [M + Na]+ calcd for C47H45O7F3Na: 801.3009; found:
801.3000.
hexane/EtOAc); IR (neat) νmax 3060, 2936, 2859, 2228, 1743, 1599, 1491,
1447, 1366, 1229, 1021, 757, 693 cm−1; 1H NMR (500MHz, CDCl3) δ
7.46–7.42 (m, 2H), 7.30–7.26 (m, 3H), 2.25–2.19 (m, 2H), 2.06 (s, 3H),
1.95–1.87 (m, 2H), 1.70–1.64 (m, 4H), 1.55 (m, 1H), 1.36 (m, 1H); 13C
NMR (100 MHz) δ 169.2, 131.8, 128.2, 128.1, 128.1, 122.8, 89.1, 86.2,
75.9, 37.1, 25.1, 22.7, 22.0 ppm; HRMS (ESI) m/z: [M + Na]+ calcd for
C16H18O2 Na: 265.1199; found: 265.1193.
1ꢀ((2ꢀBromophenyl)ethynyl)cyclohexyl acetate (3b): Following the
general procedure Pꢀ2 and Pꢀ3, 3b (900 mg, 72% yield) was obtained as
a
colorless liquid starting from cyclohexanone. Rf 0.42 (19:1
hexane/EtOAc); IR (neat) νmax 2932, 2857, 2232, 1747, 1589, 1487, 1439,
1357, 1230, 1020, 758, 691 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.55 (dd,
J = 8.0, 1.2 Hz, 1H), 7.47 (dd, J = 7.7, 1.7 Hz, 1H), 7.22 (td, J = 7.6, 1.2
Hz, 1H), 7.13 (td, J = 8.0, 1.7 Hz, 1H), 2.34ꢀ2.26 (m, 2H), 2.07 (s, 3H),
1.93ꢀ1.84 (m, 2H), 1.83ꢀ1.66 (m, 4H), 1.59 (m, 1H), 1.35 (m, 1H) ppm;
13C NMR (100 MHz) δ 169.1, 133.5, 132.2, 129.3, 126.8, 125.5, 124.9,
93.7, 84.8, 75.9, 37.0, 25.2, 22.7, 21.9 ppm; HRMS (ESI) m/z: [M + Na]+
calcd for C16H17O2BrNa 343.0304; found: 343.0296.
(2R,5S)ꢀ2ꢀIsopropylꢀ5ꢀmethylꢀ1ꢀ(phenylethynyl)cyclohexyl
acetate
(6ʹ): Following the general procedure Pꢀ2 and Pꢀ3, 6ʹ (100 mg, 40% yield)
was obtained as a colorless liquid starting from (2R,5S)ꢀ2ꢀisopropylꢀ5ꢀ
methylcyclohexanone; Rf 0.59 (19:1 hexane/EtOAc); IR (neat) νmax 3060,
2937, 2861, 2223, 1743, 1600, 1492, 1448, 1361, 1223, 1022, 757 cm−1;
1H NMR (500 MHz, CDCl3) δ 7.46–7.43 (m, 2H), 7.31–7.27 (m, 3H), 2.80
(ddd, J = 12.1, 3.3, 1.8 Hz, 1H), 2.19 (dtd, J = 13.9, 6.9, 3.1 Hz, 1H), 2.05
(s, 3H), 1.85 (m,1H), 1.77–1.70 (m, 2H), 1.50 (m, 1H), 1.42–1.24 (m, 2H),
1.01 (dd, J = 12.6, 6.9 Hz, 6H), 0.93 (d, J=6.561, 3H) ppm; 13C NMR (125
MHz, CDCl3) δ 169.2, 131.7, 128.1, 128.2, 122.9, 88.3, 87.7, 80.3, 51.3,
45.8, 34.6, 30.2, 27.0, 24.3, 23.8, 22.3, 21.8, 18.7 ppm; HRMS (ESI) m/z:
[M + Na]+ calcd for C20H26NaO2 321.1825; found: 321.1827.
3ꢀEthylꢀ1ꢀphenylpentꢀ1ꢀynꢀ3ꢀyl acetate (3c): Following the general
procedure Pꢀ2 and Pꢀ3, 3c (80 mg, 69% yield) was obtained from 3ꢀ
pentanone as a colorless liquid; Rf 0.47 (19:1 hexane/EtOAc); IR (neat)
νmax 2927, 2854, 1740, 1638, 1600, 1499, 1445, 1076, 1020, 745, 691
1
cm−1; H NMR (500 MHz, CDCl3) δ 7.38–7.34 (m, 2H), 7.22–7.18 (m, 3H),
2.09–2.01 (m, 2H), 1.96 (s, 3H), 1.91 (m, 2H), 0.96 (t, J = 7.5 Hz, 6H).
13C NMR (125 MHz, CDCl3) δ 169.2, 131.8, 128.2, 128.1, 122.7, 88.5,
85.8, 80.3, 30.8, 21.8, 8.4 ppm; HRMS (ESI) m/z: [M + Na]+ calcd for
C15H18O2Na 253.1199; found: 253.1205.
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10.1002/ejoc.201900941
European Journal of Organic Chemistry
FULL PAPER
III Experimental procedure and analytical data for hydration
products:
103.2, 103.0, 102.8, 67.6, 45.3, 20.4 ppm; 19F NMR (376 MHz, CDCl3) δ
−109.4 ppm; HRMS (APCI) m/z: [M ꢀ H]+ calcd for C11H9F2O3 227.0517;
found: 227.0507.
General procedure for hydration (Pꢀ4): To the stirred solution of γꢀ
acetoxy phenyl acetylene (1.0 mmol) in 1,4ꢀdioxane (2 mL) Ph3PAuCl
(0.01 mmol) and AgSbF6 (0.01 mmol) were added and the reaction
mixture stirred at ambient temperature. Distilled water (1.5 mmol) was
added to the above reaction mixture at the same temperature and the
resulting reaction mixture was stirred for the respective time shown in
manuscript. After completion of the reaction (monitored by TLC), the
solvent was evaporated under reduced pressure and crude residue was
purified by silica gel column chromatography.
2ꢀOxoꢀ3ꢀphenylpropyl acetate (2f): Following the general procedure Pꢀ
4, 2e (61 mg, 55% yield) as a colorless liquid was obtained starting from
1e (100 mg, 0.58 mmol); Rf 0.40 (17:1 hexane/EtOAc); 1H NMR (500
MHz, CDCl3) δ 7.36–7.32 (m, 2H), 7.28 (m, 1H), 7.23–7.20 (m, 2H), 4.69
(s, 2H), 3.74 (s, 2H), 2.15 (s, 3H) ppm; 13C NMR (125 MHz, CDCl3) δ
201.2, 170.2, 132.7, 129.4, 128.9, 127.4, 67.5, 46.4, 20.4 ppm; HRMS
(ESI) m/z: [M + H]+ calcd for C11H13O3 193.0859; found: 193.0870.
2ꢀOxoꢀ3ꢀ(pꢀtolyl)propyl acetate (2g): Following the general procedure
Pꢀ4, 2f (15 mg, 46% yield) as a colorless liquid was obtained starting
from 1f (30 mg, 0.16 mmol). Rf 0.42 (9:1 hexane/EtOAc); IR (neat) νmax
2923, 2853, 1737, 1647, 1515, 1413, 1377, 1232, 1046, 772 cm–1; 1H
NMR (500 MHz, CDCl3) δ 7.15 (d, J = 7.9 Hz, 2H), 7.10 (d, J = 8.1 Hz,
2H), 4.68 (s, 2H), 3.70 (s, 2H), 2.33 (s, 3H), 2.15 (s, 3H) ppm; 13C NMR
(100 MHz, CDCl3) δ 201.5, 170.2, 137.1, 129.6, 129.2, 128.2, 67.4, 46.1,
21.1, 20.5 ppm; HRMS (ESI) m/z: [M + H]+ calcd for C12H15O3 207.1016;
found: 207.1013.
3ꢀ(3ꢀNitrophenyl)ꢀ2ꢀoxopropyl acetate (2a): Following the general
procedure Pꢀ4, 2a (92 mg, 87% yield) as a colorless liquid was obtained
from 1a (100 mg, 0.46 mmol). Rf 0.32 (9:1 hexane/EtOAc); IR (neat) νmax
2924, 2853, 1736, 1528, 1462, 1374, 1351, 1233, 1043, 810, 712 cm–1;
1H NMR (500 MHz, CDCl3) δ 8.16 (td, J = 7.3, 2.1 Hz, 1H), 8.09 (s, 1H),
7.56–7.51 (m, 2H), 4.75 (s, 2H), 3.88 (s, 2H), 2.18 (s, 3H) ppm; 13C NMR
(100 MHz, CDCl3) δ 200.0, 170.2, 135.8, 134.4, 129.6, 124.6, 122.5, 67.8,
45.0, 20.4 ppm; HRMS (ESI) m/z: [M + Na]+ calcd for C11H11NO5Na
260.0529; found: 260.0516.
1ꢀ(3ꢀNitrophenyl)ꢀ2ꢀoxoꢀ3ꢀphenylpropyl acetate (2h): Following the
general procedure Pꢀ4, 2g ( 38 mg, 74% yield) (mp – 62 oC) as a yellow
color solid was obtained starting from 1g (50 mg, 0.17 mmol). Rf 0.40
(17:3 hexane/EtOAc ); IR (neat) νmax 2928, 2856, 2134, 1741, 1709,
1591, 1477, 1420, 1360, 1237, 1101, 715, 691 cm–1; 1H NMR (500MHz,
CDCl3) δ 8.20 (dddd, J= 8.2, 2.3, 1.2, 1.1 Hz, 1H) 8.12 (t, J = 1.9 Hz, 1H),
7.64 (d, J =7.7 Hz, 1H), 7.53 (t, J = 8.0 H, 2H), 7.28ꢀ7.22 (m, 3H), 7.07ꢀ
7.04 (m, 2H), 6.12 (s, 1H), 3.80 (s, 2H), 2.21 (s, 3H) ppm; 13C NMR (125
MHz, CDCl3) δ 200.8, 169.6,148.1, 135.0, 133.6, 131.9, 129.6, 129.3,
128.5, 127.2, 123.8, 122.7, 78.4, 46.2, 20.3 ppm; HRMS (APCI) m/z: [M
ꢀ H]+ calcd for C17H14NO5 312.0866; found: 312.0867.
3ꢀ(3ꢀFluorophenyl)ꢀ2ꢀoxopropyl acetate (2b): Following the general
procedure Pꢀ4, 2b (38 mg, 83% yield) as a colorless liquid was obtained
starting from 1b (50 mg, 0.26 mmol). Rf 0.45 (9:1 hexane/EtOAc); IR
(neat) νmax 2928, 2854, 1736, 1616, 1590, 1488, 1374, 1234, 1046, 942,
873, 786, 702 cm–1; 1H NMR (500 MHz, CDCl3) δ 7.31 (m, 1H), 7.02–
6.96 (m, 2H), 6.94 (m, 1H), 4.70 (s, 2H), 3.74 (s, 2H), 2.16 (s, 3H) ppm;
13C NMR (100 MHz, CDCl3) δ 200.6, 170.1, 164.1, 161.6, 134.9, 134.9,
130.3, 130.2, 125.1, 125.1, 116.6, 116.3, 114.5, 114.3, 67.5, 45.7, 20.4
ppm; 19F NMR (375 MHz, CDCl3) δ −112.6 ppm; HRMS (ESI) m/z: [M +
H]+ calcd for C11H12FO3 211.0765; found: 211.0758.
3ꢀ(4ꢀFluorophenyl)ꢀ2ꢀoxopropyl acetate (2c): Following the general
procedure Pꢀ4, 2c (38 mg, 87% yield) as a colorless liquid was obtained
starting from 1c (40 mg, 0.21 mmol). Rf 0.46 (9:1 hexane/EtOAc); IR
(neat) νmax 2924, 2853, 1731, 1604, 1510, 1412, 1375, 1235, 1214, 1042,
827 cm–1; 1H NMR (500 MHz, CDCl3) δ 7.18 (dd, J = 8.6, 5.3 Hz, 2H),
7.03 (t, J = 8.7 Hz, 2H), 4.69 (s, 2H), 3.72 (s, 2H), 2.16 (s, 3H) ppm; 13C
NMR (100 MHz, CDCl3) δ 201.0, 170.2, 163.4, 160.9, 131.0, 130.9,
128.4, 115.8, 115.6, 67.5, 45.3, 20.4 ppm; HRMS (APCI) m/z: [M + H]+
calcd for C11H12FO3 211.0765; found: 211.0783.
1ꢀ(4ꢀFluorophenyl)ꢀ2ꢀoxoꢀ3ꢀphenylpropyl acetate (2i): Following the
general procedure Pꢀ4, 2h (41 mg, 77% yield) as a pale yellow color
liquid was obtained starting from 1h (50 mg, 0.19 mmol). Rf 0.50 (19:1
hexane/EtOAc); IR (neat) νmax 2912, 2861, 1741, 1713, 1499, 1427,
1372, 1236, 1108, 907, 739, 704 cm–1; 1H NMR (400 MHz, CDCl3) δ
7.33–7.29 (m, 2H), 7.27–7.23 (m, 3H), 7.10–7.01 (m, 4H), 6.03 (s, 1H),
3.71 (s, 2H), 2.16 (s, 3H) ppm; 13C NMR (100 MHz): δ 201.4, 170.2,
132.7, 130.4, 130.3, 129.6, 128.7, 128.4, 127.2, 116.0, 116.0 79.3, 46.0,
20.6 ppm; 19F NMR (376 MHz, CDCl3) δ −111.47 ppm; HRMS (ESI) m/z:
[M + Na]+ calcd for C17H15FNaO3 [M + Na]+: 309.0897; found: 309.0890.
2ꢀoxoꢀ3ꢀ(2ꢀ(Trifluoromethyl)phenyl)propyl acetate (2d): Following the
general procedure Pꢀ4, 2d (43 mg, 79% yield) as a colorless liquid was
obtained starting from 1d (50 mg, 0.21 mmol). Rf 0.32 (9:1
hexane/EtOAc); IR (neat) νmax 2931, 1752, 1430, 1320, 1236, 1164,
3ꢀOxoꢀ1,4ꢀdiphenylbutanꢀ2ꢀyl acetate(2j): Following the general
procedure Pꢀ4, 2j (33 mg, 62% yield) as a colorless liquid was obtained
from 1j (50 mg, 0.19 mmol); Rf 0.40 (9:1 hexane/EtOAc); IR (neat) νmax
1
1109, 1048, 772 cm–1; H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 7.8 Hz,
2923, 2853, 1735, 1601, 1494, 1452, 1373, 1233, 1031, 701 cm–1 1H
;
1H), 7.54 (t, J = 7.5 Hz, 1H), 7.41 (t, J = 7.7 Hz, 1H), 7.32 (d, J = 7.6 Hz,
1H), 4.72 (s, 2H), 3.93 (d, J = 1.1 Hz, 2H), 2.16 (s, 3H) ppm; 13C NMR
(101 MHz, CDCl3) δ 200.0, 170.2, 132.8, 132.0, 131.2, 129.0, 128.7,
127.6, 126.2, 126., 125.6, 122.9, 120.2, 67.6, 42.8, 20.4 ppm; 19F NMR
(376 MHz, CDCl3) δ −59.9 ppm; HRMS (ESI) m/z: [M + Na]+ calcd for
C12H11F3O3Na 283.0558; found: 283.0536.
NMR (400 MHz, CDCl3) δ 7.34–7.24 (m, 6H), 7.17–7.12 (m, 2H), 7.12–
7.07 (m, 2H), 5.29 (dd, J = 8.0, 5.3 Hz, 1H), 3.72 (d, J = 16.6 Hz, 1H),
3.59 (d, J = 16.6 Hz, 1H), 3.00 (qd, J = 14.1, 6.7 Hz, 2H), 2.07 (s, 3H)
ppm; 13C NMR (100 MHz, CDCl3) δ 204.8, 170.4, 135.8, 132.8, 129.7,
129.4, 128.6, 127.2, 127.0, 78.4, 47.0, 37.0, 20.6 ppm; HRMS (ESI) m/z:
[M + H]+ calcd for C18H19O3 283.1329; found: 283.1322.
3ꢀ(3,5ꢀDifluorophenyl)ꢀ2ꢀoxopropyl acetate (2e): Following the general
procedure Pꢀ4, 2e (46 mg, 85% yield) as a colorless liquid was obtained
starting from 1e (50 mg, 0.24 mmol). Rf 0.48 (9:1 hexane/EtOAc); IR
(neat) νmax 2921, 2859, 1441, 1691, 1589, 1469, 1369, 1211, 1082 cm–1;
1H NMR (400 MHz, CDCl3) δ 6.79–6.71 (m, 3H), 4.71 (s, 2H), 3.73 (s,
2H), 2.17 (s, 3H) ppm; 13C NMR (125 MHz, CDCl3) δ 199.9, 170.2, 164.1,
164.0, 162.1, 162.0, 136.1, 136.1, 136.0, 112.6, 112.6, 112.5, 112.4,
4ꢀ(3ꢀNitrophenyl)ꢀ3ꢀoxoꢀ1ꢀphenylbutanꢀ2ꢀyl acetate (2k): Following
the general procedure Pꢀ4, 2k (28 mg, 89% yield) (mp – 94 oC) as a
colorless solid was obtained starting from 1k (30 mg, 0.09 mmol). Rf
0.31 (9:1 hexane/EtOAc); IR (neat) νmax 3031, 2927, 1735, 1529, 1373,
1351, 1235, 1049, 702 cm–1; 1H NMR (500 MHz, CDCl3) δ 8.11 (m, 1H),
7.79 (t, J = 1.8, 1H), 7.46 (t, J = 7.9, 1H), 7.39–7.29 (m, 4H), 7.22–7.18
(m, 2H), 5.29 (t, J = 6.8, 1H), 3.77 (d, J = 17.6 Hz, 1H), 3.48 (d, J = 17.6
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900941
European Journal of Organic Chemistry
FULL PAPER
Hz, 1H), 3.12 (d, J = 6.8, 2H), 2.14 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3) δ 204.0, 170.5, 148.1, 136.1, 135.0, 134.6, 129.5, 129.2, 128.8,
127.4, 124.7, 122.1, 78.5, 46.3, 37.1, 20.5 ppm; HRMS (APCI) m/z: [M +
H]+ calcd for C18H18NO5 328.1179; found: 350.1183.
45.9, 36.2, 35.5, 34.9, 34.3, 31.5, 31.4, 20.9, 20.6, 20.5 ppm; HRMS
(ESI) m/z: [M + Na]+ calcd for C23H26O5Na 405.1672; found: 405.1662.
2ꢀOxoꢀ1ꢀphenyloctanꢀ3ꢀyl acetate (2q): Following the general
procedure Pꢀ4, 2q (64 mg, 60% yield) as a colorless liquid was obtained
starting from 1q (100 mg, 0.41 mmol); Rf 0.50 (9:1 hexane/EtOAc); IR
(neat) νmax 2929, 2861, 1728, 1606, 1465, 1376, 1237, 1034, 711 cm–1;
1H NMR (400 MHz, CDCl3) δ 7.35–7.30 (m, 2H), 7.26 (m, 1H), 7.20–7.17
(m, 2H), 5.09 (dd, J = 7.7, 4.9 Hz, 1H), 3.80 (d, J = 16.2 Hz, 1H), 3.75 (d,
J = 16.2 Hz, 1H), 2.12 (s, 3H), 1.74–1.67 (m, 2H), 1.38–1.21 (m, 6H),
0.87 (t, J = 6.9 Hz, 3H) ppm; 13C NMR (125 MHz, CDCl3) δ 204.8, 170.6,
133.1, 129.6, 128.6, 127.1, 78.2, 45.9, 31.3, 30.4, 24.8, 22.3, 20.6, 13.9
ppm; HRMS (APCI) m/z: [M + H]+ calcd for C16H23O3 263.1641; found:
263.1646.
2ꢀOxoꢀ1,5ꢀdiphenylpentanꢀ3ꢀyl acetate(2l): Following the general
procedure Pꢀ4, 2l (82 mg, 77% yield) as a colorless liquid was obtained
starting from 1l (100 mg, 0.36 mmol). Rf 0.38 (17:3 hexane/EtOAc); 1H
NMR (500 MHz, CDCl3) δ 7.34–7.26 (m, 5H), 7.21 (m, 1H), 7.18–7.14 (m,
2H), 7.12–7.08 (m, 2H), 5.09 (dd, J = 7.5, 5.2 Hz, 1H), 3.78 (d, J = 16.1
Hz, 1H), 3.72 (d J=16.1 Hz, 1H), 2.72–2.60 (m, 2H), 2.14 (s, 3H), 2.05–
2.0 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ 204.6, 170.5, 140.3,
132.9, 129.6 128.7, 128.6, 128.4, 127.2, 126.3, 46.0, 32.0, 31.4, 20.6
ppm; HRMS (ESI) m/z: [M + Na]+ calcd for C19H21O3 297.1485; found:
297.1482.
2ꢀOxoꢀ1ꢀphenyloctadecanꢀ3ꢀyl acetate (2r): Following the general
procedure Pꢀ4, 2r ( 33 mg, 63% yield) as a colorless liquid was obtained
starting from 1r (50 mg, 0.13 mmol); Rf 0.46 (19:1 hexane/EtOAc); IR
(neat) νmax 2924, 2853, 1742, 1495, 1460, 1373, 1232, 1033, 706 cm–1;
1H NMR (400 MHz, CDCl3) δ 7.35–7.24 (m, 3H), 7.21–7.17 (m, 2H), 5.09
(dd, J = 7.7, 4.9 Hz, 1H), 3.80 (d, J = 16.2 Hz, 1H), 3.75 (d, J = 16.2 Hz,
1H), 2.12 (s, 3H), 1.75–1.66 (m, 2H), 1.34–1.22 (m, 26H), 0.88 (t, J = 6.8
Hz, 3H) ppm; 13C NMR (125 MHz, CDCl3) δ 204.8, 170.6, 133.1, 129.6,
128.6, 127.1, 78.2, 45.9, 31.9, 30.4, 29.7, 29.7, 29.6, 29.5, 29.4, 29.3,
29.2, 25.2, 22.7, 20.6, 14.1 ppm; HRMS (ESI) m/z: [M + Na]+ calcd for
C26H42O3Na 425.3026; found: 425.3001.
1ꢀ(3ꢀNitrophenyl)ꢀ2ꢀoxoꢀ5ꢀphenylpentanꢀ3ꢀyl acetate (2m): Following
the general procedure Pꢀ4, 2m (38 mg, 90% yield) as a colorless liquid
was obtained starting from 1m (40 mg, 0.21 mmol). Rf 0.50 (4:1
hexane/EtOAc); IR (neat) νmax 3215, 2922, 2851, 1691, 1634, 1583, 1472,
1387, 1209, 1082 cm–1; 1H NMR (500 MHz, CDCl3) δ 8.13 (dt, J = 7.4,
2.1 Hz, 1H), 8.00 (s, 1H), 7.51–7.45 (m, 2H), 7.33–7.27 (m, 2H), 7.23 (m,
1H), 7.15 (m, 2H), 5.07 (dd, J = 7.3, 6.6 Hz, 1H), 3.90 (d, J = 17.1 Hz,
1H), 3.79 (d, J = 17.1 Hz, 1H), 2.81–2.67 (m, 2H), 2.18 (s, 3H), 2.14–2.09
(m, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ 203.3, 170.6, 148.2, 140.0,
135.9, 134.8, 129.4, 128.6, 128.4, 126.4, 124.6, 122.3, 77.5, 44.8, 31.9,
31.3, 20.5 ppm; HRMS (ESI) m/z: [M + Na]+ calcd for C19H19NO5Na
364.1261; found: 364.1265.
1ꢀ(1ꢀHydroxycyclohexyl)ꢀ2ꢀphenylethanone(4a): Following the general
procedure Pꢀ4, 4a (67 mg, 93% yield) as a colorless liquid was obtained
starting from 3a (80 mg, 0.33 mmol); Rf 0.37 (9:1 hexane/EtOAc); IR
(neat) νmax 3478, 2933, 2857, 1706, 1495, 1447, 1260, 1135, 1035, 989,
5ꢀ(Benzyloxy)ꢀ2ꢀoxoꢀ1ꢀphenylpentanꢀ3ꢀyl acetate (2n): Following the
general procedure Pꢀ4, 2n (24 mg, 46% yield) as a colorless liquid was
obtained starting from 1n (50 mg, 0.16 mmol). Rf 0.52 (4:1 hexane/ethyl
acetate; IR (neat) νmax 2924, 2853, 1722, 1455, 1378, 1275, 1113, 771,
713 cm–1; 1H NMR (500 MHz, CDCl3) δ 7.38–7.32 (m, 3H), 7.31–7.27 (m,
5H), 7.14 (d, J = 6.9, 2H), 5.29 (dd, J = 7.7, 4.5, 1H), 4.44 (dd, J = 25.9,
11.8 Hz, 2H), 3.83 (d, J = 16.4 Hz, 1H), 3.77 (d, J = 16.4 Hz, 1H), 3.57–
3.52 (m, 2H), 2.08 (s, 3H), 2.13–2.01 (m, 2H) ppm; 13C NMR (100 MHz,
CDCl3) δ 204.4, 170.3, 137.9, 133.2, 129.6, 128.6, 128.4, 127.8, 127.7,
127.0, 75.3, 73.0, 65.2, 45.9, 30.8, 20.6 ppm; HRMS (ESI) m/z: [M + Na]+
calcd for C20H22O4Na 349.1416; found: 349.1433.
757, 698 cm−1 1H NMR (400MHz, CDCl3); δ 7.35–7.24 (m, 2H), 7.26 (m,
;
1H), 7.21–7.17 (m, 2H), 3.89 (s, 2H), 3.31(s, 1H), 1.83–171 (m, 4H),
170–162(m, 3H), 1.55–1.48 (m, 2H) 1.31 (m, 1H) ppm; 13C NMR (100
MHz, CDCl3) δ 212.1, 133.8, 129.5, 128.5, 127.0, 78.5, 42.6, 33.8, 25.2,
21.0 ppm; HRMS (ESI) m/z: [M + Na]+ calcd for C14H18O2 Na241.1199;
found: 241.1193.
2ꢀ(2ꢀBromophenyl)ꢀ1ꢀ(1ꢀhydroxycyclohexyl)ethanone (4b): Following
the general procedure Pꢀ4, 4b ( 87 mg, 93% yield) as a brown color liquid
was obtained starting from 3b (100 mg, 0.31 mmol); Rf 0.36 (19:1
hexane/EtOAc); IR (neat) νmax 3478, 2933, 2857, 1701, 1490, 1441, 1231,
5ꢀ((tertꢀButyldiphenylsilyl)oxy)ꢀ2ꢀoxoꢀ1ꢀphenylpentanꢀ3ꢀyl
acetate
(2o): Following the general procedure Pꢀ4, 2o (42 mg, 81% yield) as a
colorless liquid was obtained starting from 1o (50 mg, 0.11 mmol) Rf
0.53 (4:1 hexane/ethyl acetate; IR (neat) νmax 2928, 2856, 1741, 1594,
1467, 1427, 1372, 1236, 1108, 739, 704 cm–1; 1H NMR (400 MHz,
CDCl3) δ 7.66–7.59 (m, 4H), 7.46–7.35 (m, 7H), 7.33–7.27 (m, 2H), 7.18
(d, J = 7.0, 2H), 5.35 (dd, J = 9.4, 3.5 Hz, 1H), 3.82 (d, J = 16.1 Hz, 1H),
3.77 (d, J = 16.1 Hz, 1H), 3.76– 3.69 (m, 2H), 2.04 (s, 3H), 2.00 (m, 1H),
1.85 (m, 1H), 1.05 (s, 9H) ppm; 13C NMR (100 MHz, CDCl3) δ 204.6,
170.3, 135.5, 134.8, 133.3, 133.3, 133.1, 129.8, 129.6, 128.6, 127.7,
127.1, 74.9, 59.2, 46.0, 33.1, 26.8, 20.5, 19.1 ppm; HRMS (ESI) m/z: [M
+ Na]+ calcd for C29H34O4NaSi 497.2119; found: 497.2100.
757, 698 cm−1 1H NMR (500MHz, CDCl3) δ 7.57 (dd, J = 7.9, 1.1 Hz,
;
1H), 7.29 (td, J = 7.5, 1.2 Hz, 1H), 7.19–7.13 (m, 2H), 4.09 (s, 2H), 3.27
(br s, 1H), 1.90 – 1.83 (m, 2H), 1.77 (dd, J = 16.3, 5.7 Hz, 2H), 1.73–1.68
(m, 3H), 1.66 (d, J = 14.6 Hz, 2H), 1.34 (m, 1H); 13C NMR (125 MHz,
CDCl3) δ 210.9, 134.3, 132.7, 131.8, 128.8, 127.4, 124.9, 78.5, 43.5,
34.2, 25.2, 21.1 ppm; HRMS (ESI) m/z: [M + Na]+ calcd for C14H17BrO2Na
319.0304; found: 319.0313.
3ꢀEthylꢀ3ꢀhydroxyꢀ1ꢀphenylpentanꢀ2ꢀone (4c): Following the general
procedure Pꢀ4, 4c (35 mg, 78% yield) as a brown color liquid was
obtained starting from 3c (50 mg, 0.22 mmol); Rf 0.40 (9:1
hexane/EtOAc); IR (neat) νmax 2954, 2852, 2249, 1763, 1740, 1376, 1244,
1056, 772 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.37–7.31 (m, 2H), 7.29 (m,
1H), 7.22–7.18 (m, 2H), 3.78 (s, 2H), 1.83 (qd, J = 14.2, 7.2 Hz, 4H), 0.80
(t, J =7.4 Hz, 6H); 13C NMR; (125 MHz, CDCl3) δ 211.7, 133.2, 129.6,
128.5, 127.1, 82.5, 42.7, 31.4, 7.6 ppm; HRMS (ESI) m/z: [M + Na]+ calcd
for C13H18NaO2 229.1199; found: 229.1190.
2ꢀOxoꢀ1,7ꢀdiphenylheptaneꢀ3,5ꢀdiyl diacetate (2p): Following the
general procedure Pꢀ4, 2p (52 mg, 65% yield) as a colorless liquid was
obtained starting from 1p (75 mg, 0.21 mmol); Rf 0.42 (17:1
hexane/EtOAc); 1H NMR (300 MHz, CDCl3) δ 7.36–7.23 (m, 5H), 7.22–
7.11 (m, 5H), 5.16 (ddd, J = 13.7, 8.7, 4.0 Hz, 1H), 5.03 (m, 1H), 3.88–
3.71 (m, 2H), 2.66–2.55 (m, 2H), 2.11 (s, 1.5H), 2.09 (s, 1.5H), 2.07–2.02
(m, 1H), 2.00 (s, 1.5H), 1.94 (s, 1.5H), 1.85 (m, 3H) ppm; 13C NMR (100
MHz, CDCl3) δ 204.6, 203.5, 170.5, 170.4, 170.2, 141.0, 132.9, 132.8,
129.6, 128.7, 128.4, 128.2, 127.2, 126.1, 74.8, 74.4, 70.1, 69.4, 46.0,
3ꢀhydroxyꢀ1,3ꢀdiphenylbutanꢀ2ꢀone (4d): Following the general
procedure Pꢀ4, 4d (12 mg, 26% yield) as a colorless liquid was obtained
starting from 3d (50 mg, 0.19 mmol); Rf 0.70 (19:1 hexane/EtOAc); IR
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10.1002/ejoc.201900941
European Journal of Organic Chemistry
FULL PAPER
(neat) νmax 3456, 2946, 2886, 2082, 1719, 1491, 1350, 1230, 837, 690
cm−1 1H NMR (400 MHz, CDCl3) δ 7.46 (m, 2H), 7.42 – 7.33 (m, 3H),
7.25 – 7.18 (m, 3H), 6.96 – 6.90 (m, 2H), 4.39 (s, 1H), 3.68 (s, 2H), 1.83
(s, 3H) ppm; 13C NMR (125 MHz, CDCl3) δ 209.1, 141.0, 133.6, 129.3,
128.8, 128.4, 128.3, 127.0, 126.2, 80.2, 42.2, 24.0.ppm; HRMS (ESI)
m/z: [M + Na]+ calcd for C16H16NaO2 263.1048; found: 263.1052.
anhydrous CH2Cl2 (5 mL) were reflux under nitrogen atmosphere for 3 h.
After the complete consumption of the starting material (monitored by
TLC), the reaction mixture was filtered through Celite pad, washed with
CH2Cl2 (10 mL) and the combined filtrate was concentrated under reduce
pressure. The crude product was purified by silica gel column
chromatography to yield 2pʹ (45 mg, 70% yield) as a pale yellow colour
liquid. Rf 0.51 (19:1 hexane/EtOAc); IR (neat) νmax 2939, 2868, 1748,
1606, 1465, 1376, 1237, 1030 cm–1; 1H NMR (400 MHz, CDCl3) δ 7.48ꢀ
7.33 (M, 5H), 5.76 (s, 0.5H), 5.70 (s, 0.5H), 5.26 (m, 1H), 2.11 (s, 1.5H),
2.02 (s, 1.5H), 1.85ꢀ1.63 (m, 2H), 1.37ꢀ1.19 (m, 6H), 0.87 (t, J = 6.8 Hz,
1.5H), 0.84 (t, J = 6.4 Hz, 1.5H) ppm; 13C NMR (125 MHz, CDCl3) δ
198.5, 198.5, 170.3, 170.1, 134.8, 134.6, 129.4, 129.3, 129.1, 129.0,
128.8, 76.6, 76.4, 52.0, 50.9, 31.4, 31.2, 31.2, 31.1, 24.8, 24.6, 22.3,
22.2, 20.6, 20.5, 13.9, 13.9 ppm; HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd
for C16H21NaBrO3 363.0566; found: 363.0561.
;
3ꢀ(4ꢀchlorophenyl)ꢀ3ꢀhydroxyꢀ1ꢀ(4ꢀ(trifluoromethyl)phenyl)butanꢀ2ꢀ
one (4e): Following the general procedure Pꢀ4, 4e (33 mg, 75% yield) as
a yellow color liquid was obtained starting from 3e (47 mg, 0.13 mmol); Rf
0.44 (9:1 hexane/EtOAc); EtOAc); IR (neat) νmax 3459, 3056 , 2927, 2885,
2012, 1725, 1600, 1490, 1324, 1227, 1169, 1065, 837, 715, 690 cm−1; 1H
NMR (400 MHz, CDCl3) δ 7.49 (d, J = 8.1 Hz, 2H), 7.41–7.32 (m, 4H),
7.05 (d, J = 8.1 Hz, 2H), 4.08 (s, 1H), 3.74 (s, 2H), 1.80 (s, 3H) ppm; 13
C
NMR (100 MHz, CDCl3) δ 207.7, 139.4, 137.4, 134.5, 129.7, 129.0,
127.5, 125.4, 125.4, 80.0, 42.0, 24.5 ppm; 19F NMR (376 MHz, CDCl3) δ
−62.6 ppm; HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd for C17H13ClF3O2
341.0550; found: 341.0531.
1ꢀ(1ꢀHydroxyꢀ2ꢀphenylethyl)cyclohexanol (4aʹ): NaBH4 (7 mg, 0.18
mmol) was added to the solution of 4a (40 mg, 0.18 mmol) in MeOH:THF
(1:3) (3 mL) at 0 oC. The resulting reaction mixture was stirred for 30 min
at same temperature. After completion of the reaction (monitored by
TLC), it was quenched with saturated aqueous NH4Cl solution (3 mL).
The organic solvents were removed under reduced pressure and the
aqueous layer extracted with EtOAc (3 × 6 mL). The combined organic
layers were dried over Na2SO4 and concentrated under reduced pressure.
The crude compound was purified by silica gel column chromatography
to yield 4aʹ (26 mg, 66%) as a white solid. mp.110 oC; Rf 0.34 (4:1
hexane/EtOAc); IR (neat) νmax 3478, 2923, 2859, 1492, 1436, 1251, 1232
3ꢀHydroxyꢀ3ꢀ(4ꢀnitrophenyl)ꢀ1ꢀphenylbutanꢀ2ꢀone (4f): Following the
general procedure Pꢀ4, 4f (21 mg, 57% yield) as a light yellow color liquid
was obtained starting from 3f (40 mg, 0.13 mmol); Rf 0.40 (9:1
hexane/EtOAc); IR (neat) νmax 3429, 2934, 2860, 1707, 1497, 1445, 1260,
1036, 985, 759, 695 cm−1; 1H NMR (500 MHz, CDCl3) δ 8.23 (d J = 8.9
Hz, 2H), 7.66 (d, J = 8.9 Hz, 2H), 7.25–7.21 (m, 3H), 6.97–6.92 (m, 2H),
4.25 (s, 1H), 3.75 (d, J = 16.0 Hz, 1H), 3.72 (d, J = 16.0 Hz, 1H), 1.86 (s,
3H) ppm; 13C NMR (125 MHz, CDCl3) δ 207.8, 148.3, 147.7, 132.9,
129.2, 128.6, 127.2, 123.8, 80.3, 42.7, 24.9 ppm; HRMS (APCI) m/z: [M ꢀ
H]+ calcd for C16H14NO4 284.0917; found: 284.0919.
756, 693 cm−1 1H NMR (400 MHz, CDCl3) δ 7.56 (dd, J = 0.9, 8.0 Hz,
;
1H), 7.33–7.22 (m, 4H), 7.11 (td, J = 7.9, 2.0 Hz, 1H), 3.72 (d, J = 11.0
Hz, 1H), 3.17 (dd, J = 13.7, 2.1 Hz, 1H), 2.72 (dd, J = 13.7, 10.8 Hz, 1H),
1.94 (br s, 1H), 1.85 (br s, 1H), 1.74 (dd, J = 13.0, 6.6 Hz, 2H), 1.69–1.60
(m, 6H), 1.53 (dd, J = 10.5, 5.6 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ
138.5, 133.0, 132.1, 128.2.8, 127.4, 124.8, 76.4, 73.4, 37.6, 34.4, 32.0,
25.9, 21.7, 21.6 ppm; HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd for
C14H20O2Na 243.1355; found: 243.1350.
3ꢀOxoꢀ4ꢀ(4ꢀ(trifluoromethyl)phenyl)ꢀ1ꢀ((2R,3S,4R,5R,6R)ꢀ3,4,5ꢀ
tris(benzyloxy)ꢀ6ꢀ((benzyloxy)methyl)tetrahydroꢀ2Hꢀpyranꢀ2ꢀ
yl)butanꢀ2ꢀyl acetate (5): Following the general procedure Pꢀ4, 5 (46 mg,
90% yield) as a white color solid (mp ꢀ 83 oC) was obtained starting from
5′ (50 mg, 0.06 mmol). Rf 0.38 (4:1 hexane/EtOAc); 1H NMR (500 MHz,
CDCl3) δ 7.54 (d, J = 8.1 Hz, 2H), 7.34–7.22 (m, 20H), 7.10 (dd, J = 7.1,
2.2 Hz, 2H), 5.28 (dd, J = 6.1, 4.6 Hz, 1H), 4.87 (d, J =10.9 Hz, 1H), 4.78
(d, J = 10.9 Hz, 2H), 4.70 (d, J = 11.7, 1H), 4.58 (d, J=11.7 Hz, 1H), 4.54
(d, J = 12.1 Hz, 1H), 4.42 (d, J = 10.8 Hz, 1H), 4.36 (d, J = 12.1Hz, 1H),
4.26 (m, 1H), 3.92 (d, J = 17.3 Hz, 1H), 3.83 (d, J = 17.3 Hz, 1H), 3.73–
3.57 (m, 4H), 3. 50 (dt, J = 9.5, 2.6 Hz, 1H), 3.32 (dd, J = 10.4, 2.1 Hz,
1H), 2.32 (m, 1H), 2.23 (m, 1H), 2.10 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3) δ 204.4, 170.0, 138.5, 138.1, 138.0, 137.7, 137.3, 130.2, 128.5,
128.4, 128.4, 128.0, 127.9, 127.8, 127.7, 127.7, 125.3, 125.3, 81.9, 79.1,
77.5, 75.5, 75.4, 74.9, 73.4, 73.3, 71.7, 70.5, 68.2, 45.6, 26.7, 20.7 ppm;
19F NMR (376 MHz, CDCl3) δ −62.5 ppm HRMS (ESI) m/z: [M + Na]+
calcd for C47H47O8F3Na 819.3115; found: 819.3099.
1ꢀ(Benzofuranꢀ2ꢀyl)cyclohexanol (4bʹ): K3PO4 (72 mg, 0.034 mmol)
and CuI (33 mg, 0.017 mmol, 10 mol %) were added to a solution of 4b
(50 mg, 0.17 mmol) in DMF (1.0 mL) under N2 atmosphere. The solution
was stirred at 105 °C for 6 h. After the complete consumption of the
starting material (monitored by TLC), water (4 mL) and EtOAc (6 mL)
were added to the reaction mixture at ambient temperature. The aqueous
phase was extracted with EtOAc (2 × 6 mL). The combined organic
layers were dried over Na2SO4 and concentrated under reduced pressure.
The crude residue was purified by silica gel column chromatography to
yield 4bʹ (33 mg, 88%) as a pale yellow color liquid. Rf 0.40 (9:1
hexane/EtOAc); The analytical data is in complete agreement with those
reported in the literature.[25] IR (neat) νmax 3478, 2933, 2857, 1701, 1490,
1441, 1231, 757, 698 cm−1 1H NMR (500MHz, CDCl3) δ 7.54 (m, 1H),
;
(2R,5S)ꢀ2ꢀIsopropylꢀ5ꢀmethylꢀ1ꢀ(2ꢀphenylacetyl)cyclohexyl acetate
(6): Following the general procedure Pꢀ4, 6 (45 mg, 85% yield) as a
colorless liquid was obtained starting from 6′ (50 mg, 0.06 mmol); Rf 0.48
(9:1 hexane/EtOAc); IR (neat) νmax 2934, 2860, 1710, 1497, 1445, 1260,
1036, 985, 759, 695 cm−1; 1H NMR (500MHz, CDCl3) δ 7.32 (t, J = 7.3Hz,
2H), 7.25 (m, 1H), 7.18–7.15 (m, 2H), 3.81 (d, J = 17.0 Hz, 1H), 3.77 (d,
J = 17.0 Hz, 1H), 2.82 (dd, J = 10.4, 2.1 Hz, 1H), 2.12 (s, 3H), 1.84 (m,
1H), 1.67–1.59 (m, 3H), 1.58ꢀ1.49 (m, 4H), 1.03 (m, 1H), 0.92 (d, J = 6.1
Hz, 1H), 0.90 (d, J = 6.8 Hz, 2H), 0.83 (d, J = 6.9 Hz, 2H) ppm. 13C NMR
(100 MHz, CDCl3) δ 204.9, 170.0, 133.6, 129.8, 128.4, 126.9, 91.2, 48.9,
44.6, 39.5, 34.6, 27.8, 27.7, 23.3, 22.0, 21.7, 20.5, 17.5 ppm; HRMS
(ESIꢀTOF) m/z: [M + Na]+ calcd for C20H28NaO3 339.1931; found:
339.1928.
7.45 (m, 1H), 7.26 (dt, J = 7.5, 1.0 Hz, 1H), 7.20 (dt, J = 7.5,1.0 Hz, 1H),
6.61 (d, J = 0.9 Hz, 1H), 2.10–2.03 (m, 2H), 196–1.90 (m, 3H), 1.81–174
(m, 2H), 1.63–154 (m, 2H) 1.40 (m, 1H) ppm; 13C NMR (100 MHz,
CDCl3) δ 162.9, 154.5, 128.3, 123.9, 122.6, 120.9, 111.2, 101.1, 70.6,
36.5, 25.4, 22.0 ppm;
1ꢀ(1ꢀHydroxycyclohexyl)ꢀ2ꢀphenylethanone (4aD): To a stirred solution
of 3a (100 mg, 0.42 mmol) in anhydrous 1,4ꢀdioxane (4 mL), deuterated
water (0.04 mL, 1.26 mmol), Ph3PAuCl (2 mg, 0.004 mmol) and AgSbF6
(1.5 mg, 0.004 mmol) was added and stirred to ambient temperature
under argon atmosphere. After complete consumption of starting material
(indicated by TLC), the solvent was evaporated under reduced pressure
and crude residue was purified by using column chromatography on
silica gel. 4aD (70 mg, 76% yield) as a colorless liquid; Rf 0.37 (9:1
hexane/EtOAc); IR (neat) νmax 3478, 2933, 2857, 1706, 1495, 1447, 1260,
1ꢀBromoꢀ2ꢀoxoꢀ1ꢀphenyloctanꢀ3ꢀyl acetate (2pʹ): Mixture of 2p (50 mg,
0.19 mmol), Nꢀbromosuccinimide (65 mg, 29 mmol) and HBr (0.1mL) in
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10.1002/ejoc.201900941
European Journal of Organic Chemistry
FULL PAPER
1135, 1035, 989, 757, 698 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.35–7.25
(m, 3H), 7.23–7.16 (m, 2H), 3.89 (s, 0.1H), 3.34 (s, 1H), 1.85–1.70 (m,
4H), 1.69ꢀ1.62 (m, 3H) 1.56ꢀ1.47 (d, J = 0.575 Hz, 2H), 1.30 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ 212.1, 133.8, 129.5, 128.6, 127.0, 78.5, 42.6,
33.8, 25.3, 21.0 ppm; HRMS (ESIꢀTOF) m/z: [M + Na]+ calcd for
C14H16D2O2Na 243.1325; found: 243.1330
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Acknowledgments
The authors thank Council of Scientific and Industrial Research
(CSIR), New Delhi, India, for financial support as part of the XII
Five Year Plan Programme under the title ORIGIN (CSCꢀ0108);
Manuscript Communication Number IICT/Pubs/2019/200. K.L.M.,
T.R.P and N.A.M. thank UGC and CSIR, New Delhi, India, for
financial assistance in the form of fellowships.
Keywords:
AntiꢀMarkovnikov;
Regioselective;
Carbonylꢀ
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Assisted; 5ꢀexoꢀdig; Isotope labelling.
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This article is protected by copyright. All rights reserved.

10.1002/ejoc.201900941
European Journal of Organic Chemistry
FULL PAPER
FULL PAPER
Me
Me
A
mild
and
highly
goldꢀ
Assisted Nonbenzylic
Oxidation
O
O
H
O
O
H
regioselective
PPh3AuCl/AgSbF6 (1 mol%)
G
G
catalyzed hydration of γꢀ
G'
1.5ꢀ3 equiv. H2O
O
Kishor L. Mendhekar,a,b
Tapas R. Pradhan,a N.
Arjunreddy Mallampudi,a
acetoxy
leading
aryl
to
alkynes
antiꢀ
G'
1,4ꢀdioxane, rt, max. 3 h
OAc-protected Acyloins
(from 1o and 2o substrates)
1o, 2o and 3o γ-acetoxy
OR
Markovnikov products by
the assistance of
neighboring carbonyl
group is presented.
aryl alkynes
Debendra K. Mohapatraa,b,
*
OH
H
H
a
Anti-Markonikov type regioselective
hydration via acyloxy assistance
G
G'
Page No. – Page No.
O
Free tertiary Acyloin
(from 3o substrate)
Isotopic labeling studies, 23 eaxmples
with synthetic applications
Neighboring
Carbonyl
Group Assisted Hydration
of Unsymmetrical Aryl
Alkynes
Overriding
Regular Selectivity
This article is protected by copyright. All rights reserved.