Catalyst free synthesis of α-fluoro-β-hydroxy ketones/α-fluoro-ynols via electrophilic fluorination of tertiary propargyl alcohols using Selectfluor (F-TEDA-BF4)

Article abstract of DOI:10.1039/c7ob00140a

A facile method for the synthesis of α-fluoro-β-hydroxy ketones/α-fluoro-ynols from tertiary propargyl alcohols under electrophilic fluorination conditions using F-TEDA-BF₄ has been presented. The products bear pharmaceutically important α-fluoro ketone, gem-diaryl and fluorohydrin moieties in the same molecule. Interestingly, this catalyst free protocol results in monofluorination.

Full text of DOI:10.1039/c7ob00140a

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DOI: 10.1039/C7OB00140A
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Catalyst free synthesis of α-fluoro-β-hydroxy ketones/α-fluoro-
ynols via electrophilic fluorination of tertiary propargyl alcohols
using SelectfluorTM (F-TEDA-BF4)
Received 00th January 20xx,
Accepted 00th January 20xx
Naganaboina Naveena and Rengarajan Balamurugan*a
DOI: 10.1039/x0xx00000x
A facile method for the synthesis of α-fluoro--hydroxy ketones/α-fluoro-ynols from tertiary propargyl alcohols under
electrophilic fluorination conditions using F-TEDA-BF4 has been presented. The products bear pharmaceutically important
-fluoro ketone, gem-diaryl and fluorohydrin moieties in the same molecule. Interestingly, this catalyst free protocol
results in monofluorination.
www.rsc.org/
Introduction
be obtained by the fluorination of ketones and related
deivatives.9 In the fluorination reactions of enolates generated
Fluorine incorporated organic compounds, despite their poor from ketones, α,α-difluoro ketones are often formed as
occurrence in nature,1 are fascinating compounds because of byproducts and in some cases as the main product.
their wide-spread applications. Fluorinated organic Phenylacetylenes, styrenes, allenes and vinylazides also act as
compounds are extensively used in considerable areas such as useful precursors for making

-fluorocompounds.10,5g Few
diagnostics, medicinal chemistry, pharmaceuticals and reports are available in the literature for the fluorination of
agrochemicals which eventually have made them important propargyl alcohol derivatives.11 Gouverneur group11a and
targets.2 Such widespread applicability of fluoro-organic Nevado group11b separately described the conversion of
compounds is due to the intriguing physicochemical properties propargyl acetates into α-fluoroenones using gold catalysis
of fluorine (high electronegativity and small size). C-F bond, (Scheme 1).
being strong, alters the metabolic activity of drug and affects
the pKa value of neighboring groups in the compounds
possessing it.3 In this context, incorporation of fluorine in
organic molecules gained significant interest and presently
around 20% of the commercially available pharmaceuticals
contain C-F bond.2a,c,d Further, 18F labelled compounds find
application as radiotracers in positron emission tomography
(PET).4
Introduction of fluorine in organic molecules can be
achieved either by nucleophilic fluorinating reagents (F-) or
electrophilic fluorinating reagents (F+).5 Among the fluorinating
agents, SelectfluorTM (F-TEDA-BF4)6 serves as an excellent
source of F+ as it is stable, non-hygroscopic, easy to handle and
commercially available.
Fluorine at the
the electrophilicity of the carbonyl function thereby making
flouroketones as attractive targets for various applications.
Also -fluoroketones serve as key building block in the
synthesis of different fluoro compounds.7
-Fluoroketones can
-position of a carbonyl function increases
-


Scheme 1 Construction of α-fluoro ketones
a.School of Chemistry, University of Hyderabad, Gachibowli, Hyderabad 500046,
India. E-mail: bala@uohyd.ac.in; Fax: +91-40-2301-2460
Electronic Supplementary Information (ESI) available: Copies of NMR spectra of the
new compounds. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
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Incorporating fluorine directly into an organic molecule Table 1 Optimization of reaction conditions
without a catalyst, stands fundamental. Herein, we report an
electrophilic fluorination of tertiary propargyl alcohol with F-
TEDA-BF4 under catalyst free conditions to get α-fluoro-β-
hydroxy ketones or α-fluoro-ynols. The products of this
protocol have three medicinally important structural features
Journal Name
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DOI: 10.1039/C7OB00140A
viz.

-fluoro ketone, fluorohydrin and diarylmethanol groups.
Fluorohydrin10f-i and

-fluoro- -hydroxy ketone moieties have

Entry
1
Conditiona
% Yieldb of 2a
CH3CN + 10 equiv. H2O
45
2
3
4
5
6
7
8
CH3NO2 + 10 equiv. H2O
52
72
69
nr
CH3NO2
c
CH3NO2
d
CH3NO2
CH3NO2 + O2 balloon
49
nrc
nr
H2Oc
DMSO
a
all the reactions were carried out with 1a (0.35 mmol, 1.0 equiv.) and
Figure 1 Bioactive molecules containing fluorohydrins
and diarylmethanol
F-TEDA-BF4 (0.52 mmol, 1.5 equiv.) under N2 atmosphere at 70 °C for
d
3 h, b isolated yields, c reaction was performed in open air, reaction
shown promising bioactivities.12 Gem-diaryl pharmacophore
has potential application in drug development (Figure 1).13
was performed at room temperature. nr = No Reaction.
The substrate scope of the fluorination reaction was evaluated
with different tertiary propargyl alcohols by treating them with
F-TEDA-BF4 using the condition described in the entry 3 of
Table 1. The results of these reactions are presented in the
Table 2. The starting propargyl alcohols can easily be obtained
by trivial alkynyl lithium addition to diaryl ketones.18c
Results and discussion
Tertiary propargyl alcohols are interesting substrates and are
known to undergo a variety of transformations.14 Generally, in
the reactions of tertiary propargyl alcohols allenyl carbocation
intermediates are formed under Lewis acidic conditions which
subsequently involve in further reactions. We were curious to
evaluate the reaction of such tertiary propargyl alcohols with
electrophilic fluorinating agent such as F-TEDA-BF4. It is well
known that F-TEDA-BF4 can oxidize alcohols.15 In that sense,
studying the reaction of tertiary propargyl alcohols of kind
with F-TEDA-BF4 is interesting.
1
The optimization studies were carried out on the reaction of
1a with F-TEDA-BF4 in CH3CN containing 10 equiv. of water
(Table 1, entry 1). Interestingly, the reaction resulted in 45% of
mono fluorinated product 2a. Further, the fluorination is
regioselective and occurred at the carbon next to the carbinol
carbon. When the reaction was carried out in nitromethane
with 10 equiv. of water, the yield improved to 52% (Table 1,
Figure 2 X-ray crystallographic structure of 2a
entry 2). A maximum of 72% yield was obtained when the When the aryl groups in gem diary moiety of the starting
reaction was carried out using just bottle nitromethane (Table material are different diastereomeric mixture of products were
1, entry 3).16d When the reaction was carried out under open obtained (2b
-2f, 2h-2l). Yields were generally good when the
atmosphere or under oxygen atmosphere (O2 balloon) there aryl ring attached to the carbinol carbon contained an electron
were reduction in the yield of 2a (Table 1, entries 4 and 6). withdrawing group such as F or Cl. On the other hand, electron
Other polar solvents such as water and DMSO were ineffective donating substituents on the aryl ring reduced the yield (2b
,
2h
to promote the reaction (Table 1, entries 7 and 8).
and 2l). Tertiary propargyl alcohol substrates containing alkyl
2 | J. Name., 2012, 00, 1-3
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substituent at the alkynyl carbon also underwent electrophilic carbon 3e also reacted nicely to give 4e in 60% yield.
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DOI: 10.1039/C7OB00140A
fluorination smoothly (2k-2m). However, the yields were Unfortunately, substrates like 4-phenyl-2-(thiophen-2-yl)but-3-
comparatively lesser than that obtained from the aryl yn-2-ol, 1-(hex-1-yn-1-yl)cyclopentanol, 2-methylbut-3-yn-2-ol
containing substrates. Even the propargyl ether substrate (1n did not work as the reaction resulted in a complex mixture of
3-ethoxy-1,1-diphenylprop-2-yn-1-ol) underwent electrophilic products.
fluorination reaction to result in -fluoro- -hydroxyester
,


derivative 2n. Secondary aryl propargyl alcohols such as 1,3- Table 3 Reaction of tertiary propargyl alcohols containing
diphenylprop-2-yn-1-ol did not react under the reaction alkyl substitution with F-TEDA-BF4
conditions. The structure of the product 2a was further
confirmed by single crystal X-ray structural analysis (Figure
2).17
Table 2 Scope of the electrophilic fluorination of tertiary
propargyl alcohols
Reaction Conditions: 1 equiv. of 1, 1.5 equiv of F-TEDA-BF4 all the
reactions were carried out under N2 atmosphere at 70 °C, yields obtained
are isolated yields after column chromatography, ratio in parenthesis
indicates diastereomeric ratio. dr is determined by 1H NMR ratio.
When substrate
optimized fluorination condition it resulted in the expected
mono fluorinated product Upon increasing the
stoichiometry of F-TEDA-BF4 to 2.5 equiv., difluorinated
product was obtained (Table 4). In this case also the alkyne
5 derived from tetralone was subjected to the
6
.
7
functionality did not take part in the reaction even with 2.5
equiv. of F-TEDA-BF4. When this condition (2.5 equiv. of F-
TEDA-BF4) was used in the fluorination of 3d no difluorinated
product was obtained. Instead, decrease in the yield of mono
fluorinated product 4d to 24% was noted as the reaction
showed complicated spots in TLC.
Reaction Conditions: 1 equiv. of
1, 1.5 equiv. of F-TEDA-BF4. All the
reactions were carried out under N2 atmosphere at 70 °C. Yields obtained
are isolated yields after column chromatography. Ratio in parenthesis
indicates diastereomeric ratio. dr is determined using 1H NMR.
The scope of the fluorination was further evaluated with
substrates
3 which are slightly different from 1 by the
presence of one alkyl group in the place of aryl group at the
carbinol carbon. Under similar reaction conditions, to our
surprise, these substrates
3 resulted in simple vicinal
fluorohydrin without disturbing the alkyne moiety (Table 3).
4
Reaction Conditions: aYields obtained are isolated yields after column
chromatography. bRatio in parenthesis indicates diastereomeric ratio
derived from 1H NMR.
Similar type vicinal fluorohydrin formation was reported with
tertiary benzyl alcohols by Stavber and Zupan.18 Recently,
enantioselective synthesis of fluorohydrins from allylic alcohols
is reported by Toste and co-workers.10i The striking feature of
our reaction is that, even in the presence of a triple bond such
vicinal fluorohydrin formation is preferred. The results of the
fluorination reactions are presented in Table 3. Ethyl attached
propargyl alcohol resulted in a diastereomeric mixture of 4d as
expected. Propargyl alcohol with an alkyl chain on the alkynyl
Scheme 2 Mono and difluorination of alkynyltetralone
alcohol
A plausible mechanism for the fluorination is shown in Scheme
3.16 It is assumed that electrophilic fluorine coordinates to
both the triple bond as well as hydroxyl functions as shown in
Scheme 3. Due to the coordination of fluorinium ion with
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hydroxyl water attacks regioselectively to give the product
Product
electrophilic fluorine and water.
2
.
to get the pure product 2a (61 mg, Yield 72%). Rf = 0.57 (1/5
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-1
4
can form by the elimination followed by addition of EtOAc/hexanes). Colourless solid 151-15D3O°I:C1.0.I1R03(9K/BCr7,OcBm001)4:0A
3381, 3063, 1698, 1238, 953, 690. 1H NMR (400 MHz, CDCl3): δ
7.81-7.78 (m, 2H), 7.56-7.51 (m, 3H), 7.40-7.37(m, 4H), 7.33-
7.28 (m, 3H), 7.26-7.18 (m, 3H), 6.04 (d, J = 46.4 Hz, 1H), 4.49
(s, 1H). 13C NMR (100 MHz, CDCl3): δ 198.5 (d, J = 21.0 Hz),
143.1, 142.7, 135.8, 134.1, 129.3 (d, J = 5 Hz), 128.6, 128.3,
128.2, 127.9, 127.8, 127.1, 127.1, 94.1 (d, J = 196.0 Hz), 79.4
(d, J = 20.0 Hz). 19F NMR (376 MHz, CDCl3): δ -182.9 (d, J = 48.8
Hz). HRMS (ESI) m/z calcd for C21H17FO2[M+Na]+ = 343.1110,
found = 343.1114.
2-Fluoro-3-hydroxy-1,3-diphenyl-3-(p-tolyl)propan-1-one
(2b).
The representative procedure was followed using 1,3-
diphenyl-1-(p-tolyl)prop-2-yn-1-ol (1b, 75 mg, 0.251 mmol).
Purification by column chromatography using ethyl
acetate/hexanes (1/20) resulted in product 2b (55 mg, yield
Scheme 3 Plausible mechanism
Conclusion
Overall, a catalyst free simple synthetic method for the
electrophilic mono fluorination of tertiary propargyl alcohols
with F-TEDA-BF4 has been developed. The products have
medicinally relevant structural features such as gem diaryl,
vicinal fluorohydrin and -fluoroketone moieties thereby may
find application in the development of inhibitors of protein
functions.
65%, 1:1.1 diastereomeric mixture). Rf
=
0.47 (1/5
EtOAc/hexanes). Colourless solid 113-115 °C. IR (KBr, cm-1):

3380, 3063, 1698, 1238, 946, 695. 1H NMR (400 MHz, CDCl3): δ
7.79 (d, J = 8.0 Hz, 4H), 7.55-7.45 (m, 4H), 7.40-7.35 (m, 8.6H),
7.32-7.23 (m, 7H), 7.21-7.18 (m, 2H), 7.11 (d, J = 8.0 Hz, 2H),
7.04 (d, J = 8.0 Hz, 2H), 6.02 (d, J = 46.4 Hz, 2H), 4.46 (d, J = 0.8
Hz, 1H), 4.43 (d, J = 0.8 Hz, 0.92H), 2.31 (s, 3H), 2.25 (s, 3.3H).
13C NMR (100 MHz, CDCl3): δ 198.5 (d, J = 21.0 Hz), 198.4 (d, J =
21.0 Hz), 143.2, 142.8, 140.1, 139.8, 137.6, 137.4, 135.8, 133.9,
129.3, 129.1, 128.9, 128.6, 128.3, 128.2, 127.8, 127.7, 126.9,
Experimental
General Methods
126.8, 94.1 (d, J = 195.0 Hz), 79.3 (d, J = 20.0 Hz), 21.2, 21.1. 19
F
NMR (376 MHz, CDCl3): δ -182.8 (d, J = 48.8 Hz), -182.9 (d, J =
All the reagents used in this work were obtained commercially
and used without further purification unless otherwise
mentioned. F-TEDA-BF4 was purchased and used without any
further purification. LR grade CH3NO2 was used as solvent.
Thin-layer chromatography (TLC) was performed by using silica
gel F254 coated aluminum plates and the visualization of spots
were done using UV illumination and charring the TLC plates
sprayed with Seebach solution. Column chromatography was
performed on silica gel 100−200 mesh, using ethyl acetate and
45.1 Hz). HRMS (ESI) m/z calcd for C22H19FO2[M+Na]+
357.1267, found = 357.1269.
=
3-([1,1'-Biphenyl]-4-yl)-2-fluoro-3-hydroxy-
1,3diphenylpropan-1-one (2c).
The representative procedure was followed using 1-([1,1'-
biphenyl]-4-yl)-1,3-diphenylprop-2-yn-1-ol (1c, 75 mg, 0.208
mmol). Purification by column chromatography using ethyl
acetate/hexanes (1/25) resulted in product 2c (66 mg, yield
80%, 1:1.5 diastereomeric mixture). Rf
=
0.42 (1/5
1
hexanes mixture as eluent. H, 13C and 19F NMR spectra of the
EtOAc/hexanes). Colourless solid 171-173 °C. IR (KBr, cm-1):

synthesized compounds were recorded in 400 NMR machine
3375, 3057, 1687, 1484, 958, 695. 1H NMR (400 MHz, CDCl3): δ
7.82 (t, J = 8.0 Hz, 5.5H), 7.59-7.55 (m, 12H), 7.52-7.45 (m,
3.7H), 7.47-7.39 (m, 16.6H), 7.37-7.28 (m, 8.7H), 6.07 (d, J =
46.4 Hz, 2H), 4.53 (s, 1H,), 4.51 (s, 1.5H, major). 13C NMR (100
MHz, CDCl3): δ 198.6, 198.4, 143, 142.6, 142.1, 135.8, 134.1,
134, 129.4, 129.3, 128.9, 128.6, 128.4, 128.3, 127.9, 127.5,
127.2, 127.1, 127, 94.1 (d, J = 195.0 Hz ), 79.4 (d, J = 19.0 Hz ).
19F NMR (376 MHz, CDCl3): δ -182.8 (d, J = 45.1 Hz), 182.9 (d, J
1
using their solutions in CDCl3. H, 13C and 19F NMR referred
respectively to TMS used as an internal standard and the
central line of CDCl3 peaks. IR spectra were recorded using
FT/IR spectrometer. High resolution mass spectra (HRMS)
were recorded using ESI-Q-TOF technique. Melting points were
determined by using visual melting range apparatus and are
uncorrected.
Representative procedure for electrophilic fluorination
:
= 45.1 Hz). HRMS (ESI) m/z calcd for C27H21FO2[M+Na]+
419.1423, found = 419.1430.
=
Synthesis of 2-Fluoro-3-hydroxy-1,3,3-triphenylpropan-1-one
(2a).
2-Fluoro-3-(4-fluorophenyl)-3-hydroxy-1,3-diphenylpropan-1-
one (2d).
The representative procedure was followed using 1-(4-
fluorophenyl)-1,3-diphenylprop-2-yn-1-ol (1d, 75 mg, 0.248
mmol). Purification by column chromatography using ethyl
acetate/hexanes (1/25) resulted in product 2d (71 mg, yield
1,1,3-Triphenylprop-2-yn-1-ol (1a, 75 mg, 0.264 mmol) was
weighed in a clean round bottom flask and CH3NO2 (3 mL) was
added to it. After stirring for 5 minutes, F-TEDA-BF4 (140 mg,
0.396 mmol) was added to it and stirred under nitrogen at 70
°C. After completion of the reaction, the solvent was
evaporated and the crude residue was directly loaded on a
silica gel column and eluted with ethyl acetate/hexanes (1/25)
85%, 1:1.2 diastereomeric mixture). Rf
=
0.58 (1/5
EtOAc/hexanes). Colourless solid 121-123 °C. IR (KBr, cm-1):

4 | J. Name., 2012, 00, 1-3
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1
3369, 3057, 1698, 1452, 1243, 964, 690. H NMR (400 MHz, The representative procedure was followed usiVniegw A1r,t1icl-ebOisn(li4ne-
CDCl3): δ 7.81-7.78 (m, 4H), 7.57-7.54 (m, 2H), 7.49-7.46 (m, chlorophenyl)-3-phenylprop-2-yn-1-ol 1g
DOI: 107.15039/mC7gO, B000.12410A3
(
,
4H), 7.41-7.31 (m, 9.7H), 7.29-7.21 (m, 4.4H), 6.98 (t, J = 8.8 mmol). Purification by column chromatography using ethyl
Hz, 1.9H), 6.92 (t, J = 8.8 Hz, 2.3H), 6.0 (d, J = 46.0 Hz, 1H), 5.95 acetate/hexanes (1/20) resulted in product 2g (55 mg, yield
(d, J = 46.4 Hz, 1H, major), 4.54 (s, 1H), 4.51 (s, 1H, major). 13C 67%). Rf = 0.45 (1/5 EtOAc/hexanes). Light yellow solid 127-
NMR (100 MHz, CDCl3): δ 198.6 (d, J = 21.0 Hz), 198.3, 162.3 129 °C. IR (KBr, cm-1):
 3353, 3052, 1698, 1490, 1238, 958,
1
(d, J = 242.0 Hz ), 162.2 (d, J = 238.0 Hz ), 142.9, 142.6, 138.8, 810. H NMR (400 MHz, CDCl3): δ 7.81 (d, J = 7.6 Hz, 2H), 7.59
138.5, 135.8, 135.7, 134.2, 134.1, 129.3, 129.3, 129.3, 129, (t, J = 7.6 Hz, 1H), 7.45-7.40 (m, 4H), 7.30-7.27 (m, 4H), 7.25-
128.9, 128.6, 128.4, 128.3, 128, 127.9, 126.9, 126.9, 115.2 (d, J 7.23 (m, 2H), 5.87 (d, J = 46.0 Hz, 1H), 4.61(s, 1H). 13C NMR
= 21.0 Hz), 115 (d, J = 21.0 Hz), 94.5 (d, J = 197.0 Hz), 93.9 (d, J (100 MHz, CDCl3): δ 198.5 (d, J = 22.0 Hz), 141.2, 140.9, 135.5,
= 196.0 Hz), 79.2 (d, J = 20.0 Hz), 79.1 (d, J = 19.0 Hz). 19F NMR 134.5, 134.1, 133.9, 129.4, 129.4, 128.8, 128.6, 128.5, 94.3 (d, J
(376 MHz, CDCl3): δ -114.7 (m), -182.2 (d, J = 45.1 Hz), -182.8 = 196.0 Hz), 78.7 (d, J = 19.0 Hz). 19F NMR (376 MHz, CDCl3): δ -
(d, J = 45.0 Hz). HRMS (ESI) m/z calcd for C21H16F2O2[M+Na]+ = 181.8 (d,
361.1016, found = 361.1018.
C21H15Cl2FO2[M+Na]+ = 411.0331, found = 411.0335.
3-(4-Chlorophenyl)-2-fluoro-3-hydroxy-1,3-diphenylpropan-1- 2-Fluoro-3-hydroxy-3-phenyl-1,3-di-p-tolylpropan-1-one (2h).
one (2e). The representative procedure was followed using 1-phenyl-
The representative procedure was followed using 1-(4- 1,3-di-p-tolylprop-2-yn-1-ol 1h 75 mg, 0.240 mmol).
J = 45.1 Hz). HRMS (ESI) m/z calcd for
(
,
chlorophenyl)-1,3-diphenylprop-2-yn-1-ol (1e, 75 mg, 0.235 Purification by column chromatography using ethyl
mmol). Purification by column chromatography using ethyl acetate/hexanes (1/20) resulted in product 2h (53 mg, yield
acetate/hexanes (1/20) resulted in product 2e (62 mg, yield 63%, 1:1.2 mixture of diastereomers). Rf
=
0.5 (1/5
75%, 1:1.2 diastereomeric mixture). Rf
=
0.42 (1/5 EtOAc/hexanes). Colourless solid 83-85 °C. IR (neat, cm-1):

1
EtOAc/hexanes). Colourless solid 118-120 °C. IR (KBr, cm-1):

3462, 3062, 1670, 1445, 1045, 700. H NMR (400 MHz, CDCl3):
1
3369, 3057, 1693, 1495, 1238, 958, 695. H NMR (400 MHz, δ 7.73 (d, J = 7.6 Hz, 4H), 7.49 (d, J = 7.2 Hz, 2H), 7.39-7.36 (m,
CDCl3): δ 7.82-7.79 (m, 4H), 7.58-7.55 (m, 2H), 7.48-7.38 (m, 3.9H), 7.32-7.17 (m, 13H), 7.11 (d, J = 8.0 Hz, 2H), 7.05 (d, J =
8.4H), 7.36-7.34 (m, 2H), 7.33-7.26 (m, 8.2H), 7.25-7.20 (m, 8.0 Hz, 2.2H), 5.97 (d, J = 46.4 Hz, 2H), 4.58 (s, 1H), 4.56 (s,
4H), 6.01 (dd, J = 46.0 Hz, 0. 8 Hz, 1H), 5.93 (dd, J = 46.0 Hz, 0. 0.8H), 2.38 (s, 6H), 2.31 (s, 2.6H), 2.26 (s, 3H, major). 13C NMR
8 Hz, 1H, major), 4.56 (s, 0.8H), 4.53 (s, 1H). 13C NMR (100 (100 MHz, CDCl3): δ 198.0 (d, J = 21.0 Hz), 197.9 (d, J = 21.0
MHz, CDCl3): δ 198.5 (d, J = 22.0 Hz), 198.2, 142.6, 142.4, Hz), 145.3, 143.2, 143.1, 140.2, 140.1, 137.5, 137.3, 133.3,
141.6, 141.3, 135.7, 135.6, 134.3, 134.2, 133.8, 133.7, 129.4, 129.6, 129.5, 129.4, 129, 128.9, 128.3, 128.2, 127.7, 127.6,
129.3, 128.7, 128.6, 128.5, 128.4, 128.1, 128, 126.9, 126.9, 126.9, 126.8, 94.1 (d, J = 195.0 Hz), 79.3 (d, J = 20.0 Hz), 21.9,
94.5 (d, J = 196.0 Hz), 93.9 (d, J = 195.0 Hz), 79.1 (d, J = 19.0 21.2, 21.1; 19F NMR (376 MHz, CDCl3): δ -182.6 (d, J = 45.0 Hz),
Hz), 79 (d, J = 20.0 Hz). 19F NMR (376 MHz, CDCl3): δ -182.2 (d, J -182.7 (d,
= 45.1 Hz), -182.7 (d, J = 45.1 Hz). HRMS (ESI) m/z calcd for C23H21FO2[M+Na]+ = 371.1423, found = 371.1426.
C21H16ClFO2[M+Na]+ = 377.0721, found = 377.0723.
3-([1,1'-Biphenyl]-4-yl)-2-fluoro-3-hydroxy-3-phenyl-1-(p-
3-(4-Bromophenyl)-2-fluoro-3-hydroxy-1,3-diphenylpropan-1- tolyl)propan-1-one (2i).
J = 48.0 Hz). HRMS (ESI) m/z calcd for
one (2f).
The representative procedure was followed using 1-([1,1'-
The representative procedure was followed using 1-(4- biphenyl]-4-yl)-1-phenyl-3-(p-tolyl)prop-2-yn-1-ol (1i, 75 mg,
bromophenyl)-1,3-diphenylprop-2-yn-1-ol (1f, 75 mg, 0.207 0.216 mmol). Purification by column chromatography using
mmol). Purification by column chromatography using ethyl ethyl acetate/hexanes (1/25) resulted in product 2i (57 mg,
acetate/hexanes (1/20) resulted in product 2f (63 mg, yield yield 64%, 1:1.3 mixture of diastereomers). Rf = 0.45 (1/5
77%, 1:1.1 mixture of diastereomers). Rf
= 
0.45 (1/5 EtOAc/hexanes). Colourless solid 151-153 °C. IR (KBr, cm-1):
EtOAc/hexanes). Colourless solid 140-142 °C. IR (KBr, cm-1):

3386, 1698, 1490, 1249, 969, 832. 1H NMR (400 MHz, CDCl3): δ
1
3380, 3063, 1698, 1446, 1238, 964, 701. H NMR (400 MHz, 7.76-7.72 (m, 4H), 7.60-7.55 (m, 7.8H), 7.53-7.49 (m, 2.2H),
CDCl3): δ 7.80 (m, 4H), 7.57 (t, J = 6.8 Hz, 2H), 7.48-7.45 (m, 7.44-7.41 (m, 9H), 7.35-7.26 (m, 7.6H), 7.23- 7.17 (m, 6H), 6.04
2H), 7.43-7.34 (m, 12H), 7.31-7.24 (m, 8H), 5.98 (d, J = 46.0 Hz, (d, J = 46.0 Hz, 1H), 6.02 (d, J = 46.4 Hz, 1H, major), 4.68 (s, 1H),
1H), 5.92 (dd, J = 46.0 Hz, 1H, major), 4.56 (s, 0.9H), 4.53 (s, 4.63 (s, 0.8H, major), 2.38 (s, 3.4H), 2.36 (s, 2.4H). 13C NMR
1H). 13C NMR (100 MHz, CDCl3): δ 198.6, 198.3 (d, J = 21.0 Hz), (100 MHz, CDCl3): δ 198.1, 197.8, 145.4, 145.3, 143.1, 142.8,
142.6, 142.3, 141.8, 135.7, 135.6, 134.3, 134.2, 131.4, 131.3, 142.1, 141.8, 140.7, 140.5, 133.3, 133.2, 129.5, 129.4, 128.8,
129.4, 129.3, 128.8, 128.7, 128.5, 128.4, 128.1, 128.0, 126.9, 128.4, 128.3, 127.9, 127.8, 127.5, 127.2, 126.9, 93.9 (d, J =
126.9, 122.1, 121.9, 94.4 (d, J = 196.0 Hz), 93.8 (d, J = 195.0 195.0 Hz), 79.3 (d, J = 10.0 Hz), 21.9, 21.8. 19F NMR (376 MHz,
Hz), 79.2 (d, J = 20.0 Hz), 79.1 (d, J = 20.0 Hz). 19F NMR (376 CDCl3): Proton decoupled δ -186.8, -187.4. HRMS (ESI) m/z
MHz, CDCl3): δ -182.3 (d, J = 45.1 Hz), -182.(d, J = 45.1 Hz). calcd for C28H23FO2[M+Na]+ = 433.1580, found = 433.1584.
HRMS (ESI) m/z calcd for C21H16BrFO2[M+Na]+ = 421.0215 3-(4-Bromophenyl)-2-fluoro-3-hydroxy-3-phenyl-1-(p-
found = 421.0214.
tolyl)propan-1-one (2j).
3,3-Bis(4-chlorophenyl)-2-fluoro-3-hydroxy-1-phenylpropan-
1-one (2g).
The representative procedure was followed using 1-(4-
bromophenyl)-1-phenyl-3-(p-tolyl)prop-2-yn-1-ol (1j, 75 mg,
0.198 mmol). Purification by column chromatography using
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J. Name., 2013, 00, 1-3 | 5
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ethyl acetate/hexanes (1/20) resulted in product 2j (60 mg, 2-Fluoro-1-hydroxy-1,1-diphenylheptan-3-one (2m).
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yield 73%, 1:1.1 diastereomeric mixture). Rf = 0.54 (1/5 The representative procedure was DfoOlIl:o1w0.1e0d39/uCs7iOnBg00114,01A-
EtOAc/hexanes). Colourless solid 113-115 °C. IR (KBr, cm-1):
3364, 3063, 1693, 1490, 1294, 1084, 816. H NMR (400 MHz, by column chromatography using ethyl acetate/hexanes (1/30)

diphenylhept-2-yn-1-ol (1m, 78 mg, 0.284 mmol). Purification
1
CDCl3): δ 7.47-7.14 (m, 4H), 7.47-7.46 (m, 2.5H), 7.43-7.31 (m, resulted in product 2m (43 mg, yield 50%). Rf = 0.66 (1/5
9.3H), 7.31-7.19 (m, 12.3H), 5.94 (d, J = 46.0 Hz, 1H), 5.88 (d, J EtOAc/hexanes). Colourless solid 91-93 °C. IR (KBr, cm-1):

1
= 46.4 Hz, 1H, major), 4.71 (s, 0.87H), 4.65 (s, 1H), 2.38 (s, 6H); 3397, 3063, 2958, 1720, 1446, 1063, 701; H NMR (400 MHz,
13C NMR (100 MHz, CDCl3): δ 197.9 (d, J = 22.0 Hz), 197.8 (d, J = CDCl3): δ 7.51-7.48 (m, 2H), 7.38-7.25 (m, 8H), 5.29 (d, J = 47.6
21.0 Hz), 145.6, 145.5, 142.6, 142.5, 142.3, 142, 133.1, 132.9, Hz, 1H), 4.40 (d, J = 1.2 Hz, 1H), 2.53-2.40 (m, 2H), 1.41-1.35
131.5, 131.4, 131.3, 129.5 (d, J = 5.0 Hz), 129.4 (d, J = 3.0 Hz), (m, 2H), 1.18-1.13 (m, 2H), 0.81 (t, J = 7.6 Hz, 3H). 13C NMR
129.1, 128.8, 128.6, 128.4, 128.3, 128, 127.9, 127.1, 126.9, (100 MHz, CDCl3): δ 211.8 (d, J = 25.0 Hz), 142.4, 142.1, 128.4,
126.8, 122.1, 121.8, 94.2 (d, J = 196.0 Hz), 92.6 (d, J = 195.0 128.3, 128, 127.2, 126.8, 96.8 (d, J = 198.0 Hz), 79 (d, J = 19.0
Hz), 79.1 (d, J = 20.0 Hz), 79 (d, J = 20.0 Hz), 21.9. 19F NMR (376 Hz), 40, 24.5, 22.1, 13.8. 19F NMR (376 MHz, CDCl3): δ -187.8
MHz, CDCl3): δ -182.1 (d, J = 48.8 Hz), -182.4 (d, J = 48.8 Hz). (d, J = 48.8 Hz); HRMS (ESI) m/z calcd for C19H21FO2[M+Na]+ =
HRMS (ESI) m/z calcd for C22H18BrFO2[M+Na]+ = 435.0372, 323.1423, found = 323.1426.
found = 435.0374.
Ethyl 2-fluoro-3-hydroxy-3,3-diphenylpropanoate (2n).
1-([1,1'-Biphenyl]-4-yl)-2-fluoro-1-hydroxy-1-phenylhexan-3-
one (2k).
The representative procedure was followed using 1-([1,1'- Purification
The representative procedure was followed using 3-ethoxy-
1,1-diphenylprop-2-yn-1-ol
(
1n
,
75 mg, 0.297 mmol).
chromatography using
by column
biphenyl]-4-yl)-1-phenylhex-2-yn-1-ol (1k, 75 mg, 0.23 mmol). ethylacetate/hexanes (1/14) resulted in product 2n (34 mg,
Purification by column chromatography using ethyl yield 40%). Rf = 0.42 (1/3 EtOAc/hexanes). Colourless solid
acetate/hexanes (1/30) resulted in product 2k (38 mg, yield 109-111 °C. IR (KBr, cm-1):

3408,1742, 1446, 1079, 750, 657.
0.58 (1/5 1H NMR (400 MHz, CDCl3): δ 7.57-7.55 (m, 2H), 7.41-7.34 (m,
EtOAc/hexanes). Colourless solid 121-123 °C. IR (KBr, cm-1):
4H), 7.32-7.28 (m, 3H), 7.26-7.25 (m, 1H), 5.47 (d, J = 46.8 Hz,
45%, 1:1 diastereomeric mixture). Rf
=

3364, 1720, 1446, 1068, 832, 695. 1H NMR (400 MHz, CDCl3): δ 1H), 4.13-4.03 (m, 3H), 1.03 (t, J = 7.2 Hz, 3H). 13C NMR (100
7.60-7.53 (m, 6H), 7.46-7.41 (m, 4H), 7.39-7.28 (m, 4H), 5.32 MHz, CDCl3): δ 168.7 (d, J = 24.0 Hz), 142.6, 141.6, 128.4,
(d, J = 47.6 Hz, 1H), 4.46 (dd, J = 13.6 Hz, 1.6 Hz, 1H), 2.56-2.42 128.2, 128.1, 127.9, 126.9, 126.6 (d, J = 2.0 Hz), 91.9 (d, J =
(m, 2H), 1.49-1.43 (m, 2H), 0.77 (t, J = 7.6 Hz, 3H). 13C NMR 199.0 Hz), 78.5 (d, J = 19.0 Hz), 62.1, 13.8. 19F NMR (376 MHz,
(100 MHz, CDCl3): δ 211.7 (d, J = 25.0 Hz), 211.5 (d, J = 25.0 CDCl3): δ -189.1 (d, J = 48.8 Hz). HRMS (ESI) m/z calcd for
Hz), 142.2, 141.9, 141.4, 141.1, 140.7, 140.6, 140.5, 128.8, C17H17FO3 [M+Na]+ = 311.1059, found = 311.1062.
128.7, 128.4, 128.2, 127.9, 127.5, 127.4, 127.2, 127.2, 127.1, 1-Fluoro-2,4-diphenylbut-3-yn-2-ol (4a).
126.9, 126.9, 126.7 (d, J = 3.0 Hz), 96.7 (d, J = 198.0 Hz), 78.8 The representative procedure was followed using 2,4-
(d, J = 20.0 Hz), 42.2, 42.2, 15.9, 13.5. 19F NMR (376 MHz, diphenylbut-3-yn-2-ol (3a, 75 mg, 0.337 mmol). Purification by
CDCl3): δ -187.8 (d, J = 48.8 Hz), -187.9 (d, J = 48.8 Hz). HRMS column chromatography using ethyl acetate/hexanes (1/10)
(ESI) m/z calcd for C24H23FO2 [M+Na]+ = 385.1580, found = resulted in product 4a (60 mg, yield 74%). Rf = 0.5 (1/5
385.1576.
EtOAc/hexanes). Colourless liquid. IR (neat, cm-1):
3062, 2235, 1489, 1456, 1023, 936. H NMR (400 MHz, CDCl3):

3418,
1
2-Fluoro-1-hydroxy-1-phenyl-1-(p-tolyl)hexan-3-one (2l).
The representative procedure was followed using 1-phenyl-1- δ 7.75-7.72 (m, 2H), 7.52-7.49 (m, 2H), 7.43-7.36 (m, 3H), 7.36-
(p-tolyl)hex-2-yn-1-ol (1l, 75 mg, 0.284 mmol). Purification by 7.33 (m, 3H), 4.57 (dd, J = 22.0 Hz, 8.8 Hz, 1H), 4.45 (dd, J =
column chromatography using ethyl acetate/hexanes (1/30) 22.8 Hz, 8.8 Hz, 1H), 3 (s, 1H). 13C NMR (100 MHz, CDCl3): δ
resulted in product 2l (40 mg, yield 47%, 1:1.2 mixture of 139.2, 132.1, 129, 128.8, 128.6, 128.5, 126.3, 122.1, 89 (d, J =
diastereomers). Rf = 0.5 (1/5 EtOAc/hexanes). Colourless solid 185.0 Hz), 88, 87.1, 72.7 (d, J = 19.0 Hz). 19F NMR (376 MHz,
61-63 °C. IR (neat, cm-1):
 3407, 3051, 2964, 1692, 1489, 1067, CDCl3): δ -127.5 (dd, J = 56.4, 37.6 Hz). HRMS (ESI) m/z calcd
689. 1H NMR (400 MHz, CDCl3): δ 7.49 (d, J = 8.4 Hz, 2H), 7.38- for C16H13FO[M+Na]+ = 263.0848, found = 263.0847.
7.36 (m, 4.3H), 7.34-7.30 (m, 4H), 7.29-7.28 (m, 1H), 7.26-7.24 2-(4-Bromophenyl)-1-fluoro-4-phenylbut-3-yn-2-ol (4b).
(m, 3H), 7.16-7.11 (m, 4H), 5.28 (d, J = 47.6 Hz, 1H), 5.27 (d, J = The representative procedure was followed using 2-(4-
47.6 Hz, 1H), 4.33 (d, J = 1.6 Hz, 1H, major), 4.32 (d, J = 2.0 Hz, bromophenyl)-4-phenylbut-3-yn-2-ol (3b, 75 mg, 0.249 mmol).
0.8H), 2.52-2.49 (m, 2H), 2.43-2.38 (m, 2H), 2.36 (s, 3H), 2.32 Purification by column chromatography using ethyl
(s, 3H), 1.49-1.41 (m, 4H), 0.76 (m, 6H). 13C NMR (100 MHz, acetate/hexanes (1/10) resulted in product 4b (52 mg, yield
CDCl3): δ 211.6 (d, J = 25.0 Hz), 211.4 (d, J = 26.0 Hz), 142.4, 65%). Rf = 0.5 (1/5 EtOAc/hexanes). Colourless liquid IR (neat,
142.2, 139.4, 139.1, 137.6, 137.6, 128.9, 128.8, 128.3, 128.1, cm-1):

3435, 2235, 1396, 1007, 821. 1H NMR (400 MHz,
127.8, 127, 126.9 (d, J = 1.0 Hz), 126.8, 126.7, 126.7, 126.6, CDCl3): δ 7.59-7.57 (m, 1H), 7.54-7.47 (m, 2H), 7.45-7.41 (m,
96.8 (d, J = 198.0 Hz), 96.7 (d, J = 198.0 Hz), 78.8 (d, J = 19.0 2H), 7.36-7.28 (m, 4H), 4.50 (dd, J = 47.2 Hz, 9.2 Hz, 1H), 4.41
Hz), 42.1, 42.0, 21.1, 15.8 (d, J = 2.0 Hz), 15.7 (d, J = 2.0 Hz), (dd, J = 47.6 Hz, 9.2 Hz, 1H), 3.06 (s, 1H). 13C NMR (100 MHz,
13.4, 13.4. 19F NMR (376 MHz, CDCl3): δ -187.9 (d, J = 48.8 Hz), CDCl3): δ 138.4, 132.1, 131.7, 129.2, 128.5, 128.1, 123, 121.7,
-188 (d,
J =
48.8 Hz). HRMS (ESI) m/z calcd for 89.6, 88.7 (d, J = 185.0 Hz), 87.4, 72.2 (d, J = 20.0 Hz). 19F NMR
C19H21FO2[M+Na]+ = 323.1423, found = 323.1424.
(376 MHz, CDCl3): δ 127.4 (dd, J = 56.4 Hz, 7.5 Hz). HRMS (ESI)
6 | J. Name., 2012, 00, 1-3
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ARTICLE
yield 82%, 1:2 mixture of diastereomers). Rf = 0.59 (1/3
m/z calcd for C16H12BrFO[M+Na]+
340.9956.
2-(2-Bromophenyl)-1-fluoro-4-phenylbut-3-yn-2-ol (4c).
= 340.9953, found =
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EtOAc/hexanes). Colourless liquid. IR (neat, cm-1):

DOI: 10.1039/C7OB030414204A,
3062, 2947, 2218, 1495, 1051, 700. H NMR (400 MHz, CDCl3):
1
The representative procedure was followed using 2-(2- δ 7.90-7.87 (m, 1H major), 7.85-7.83 (m, 0.5H), 7.43-7.41 (m,
bromophenyl)-4-phenylbut-3-yn-2-ol (3c, 75 mg, 0.249 mmol). 3H), 7.29-7.23 (m, 7.3H), 7.11-7.09 (m, 1.5H), 5.05 (ddd, J =
Purification by column chromatography using ethyl 49.2 Hz, 8.4 Hz, 3.2 Hz, 1H major), 4.85 (ddd, J = 49.2 Hz, 7.6
acetate/hexanes (1/10) resulted in product 4c (48 mg, yield Hz, 4.4 Hz, 0.5H), 3.13 (s, 0.5H), 3.04-3 (m, 2.5H), 2.91-2.81 (m,
61%). Rf = 0.41 (1/5 EtOAc/hexanes). Colourless liquid. IR 1.5H), 2.41-2.24 (m, 3H). 13C NMR (100 MHz, CDCl3): δ 136.9,
(neat, cm-1):

3451, 3062, 2224, 1467, 1018; 1H NMR (400 136.9, 134.6, 134.4, 131.9, 131.8, 128.9, 128.7, 128.7, 128.6,
MHz, CDCl3): δ 7.94-7.92 (m, 1H), 7.64 (dd, J = 8.0 Hz, 1.2 Hz, 128.5, 128.5, 128.3, 128.3, 127.9, 127, 122.3, 122.2, 94 (d, J =
1H), 7.48 (dd, J = 7.6 Hz, 1.2 Hz, 2H), 7.42-7.37 (m, 1H), 7.32- 181.0 Hz), 93.8 (d, J = 181.0 Hz), 89.6, 89, 87.2, 86.3, 70.8 (d, J
7.29 (m, 3H), 7.24-7.19 (m, 1H), 5.04 (dd, J = 46.8 Hz, 9.2 Hz, = 21.0 Hz), 69.5 (d, J = 21.0 Hz), 25.8 (d, J = 9.0 Hz), 25.6 (d, J =
1H), 4.74 (dd, J = 47.2 Hz, 9.2 Hz, 1H), 3.3 (s, 1H). 13C NMR (100 10.0 Hz), 25. (d, J = 19.0 Hz), 24.4 (d, J = 19.0 Hz). 19F NMR (376
MHz, CDCl3): δ 137.4, 135.1, 131.9, 130.2, 128.9, 128.6, 128.4, MHz, CDCl3): δ -187.5 (m), -191.3 (dd, J = 48.8 Hz, 22.5 Hz);
127.8, 122.2, 121.1, 87.6, 86.7 (d, J = 5.0 Hz), 86.3 (d, J = 190.0 HRMS (ESI) m/z calcd for C18H15FO[M]+ = 266.1107, found =
Hz), 72.1 (d, J = 20.0 Hz). 19F NMR (376 MHz, CDCl3): δ proton 266.1106.
decoupled
-129.9, -129.6. HRMS (ESI) m/z calcd for 2,2-Difluoro-1-(phenylethynyl)-1,2,3,4-tetrahydronaphthalen-
C16H12BrFO[M+Na]+ = 340.9953, found = 340.9953.
1-ol (7).
4-Fluoro-1,3-diphenylpent-1-yn-3-ol (4d).
The representative procedure was followed using 2-fluoro-1-
The representative procedure was followed using 1,3- (phenylethynyl)-1,2,3,4-tetrahydronaphthalen-1-ol (6, 75 mg,
diphenylpent-1-yn-3-ol (3d, 75 mg, 0.317 mmol). Purification 0.302 mmol) and 2.5 equiv. of F-TEDA-BF4. Purification by
by column chromatography using ethyl acetate/hexanes (1/10) column chromatography using ethyl acetate/hexanes (1/7)
resulted in product 4d (68 mg, yield 85%, 1:1.5 mixture of resulted in product
7 (57 mg, yield 66%). Rf = 0.42 (1/3
diastereomers). Rf = 0.45 (1/5 EtOAc/hexanes). Colourless EtOAc/hexanes). Colourless solid 74-76 °C. IR (KBr, cm-1):
liquid. IR (neat, cm-1):

3440, 3068, 2224, 1489, 1034, 695; H 3567, 3063, 2230, 1495, 1216, 756. 1H NMR (400 MHz,
1
NMR (400 MHz, CDCl3): δ 7.72-7.68 (m, 2.8H), 7.53-7.47 (m, CDCl3): δ 7.91-7.88 (m, 1H), 7.48-7.47 (m, 2H), 7.32-7.30 (m,
3H), 7.39-7.36 (m, 2.9H), 7.35-7.31 (m, 5.8H), 4.83 (ddd, J = 5H), 7.16-7.15 (m, 1H), 3.16-3.05 (m, 2H), 3.02 (s, 1H), 2.64-
46.8 Hz, 12.4 Hz, 6.0 Hz, 0.5H), 4.75 (ddd, J = 48.4 Hz, 12.4 Hz, 2.39 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 136.2, 133.5, 132.1,
6.4 Hz, 1H major), 3.25 (s, 1H), 2.88 (s, 0.5H), 1.38-1.26 (m, 129.2, 129.1, 128.9, 128.6, 128.4, 127.2, 121.9, 121.4 (t, J =
4.5H). 13C NMR (100 MHz, CDCl3): δ 140.4, 139.6, 132, 128.9, 240.0 Hz), 87.5, 86.4, 71.2 (m), 26.9 (t, J = 23.0 Hz), 26.4 (m).
128.8, 128.7, 128.4, 128.3, 126.7, 126.5, 122.2, 95.5 (d, J = 19F NMR (376 MHz, CDCl3): δ -110.1 (ddd, J = 240.6, 26.3, 7.5
180.0 Hz), 94.4 (d, J = 180.0 Hz), 88.9, 88.1, 87.4, 86.9, 76.4 (d, Hz), -112.9 (dd, J = 236.8, 15 Hz). HRMS (ESI) m/z calcd for
J = 20.0 Hz), 74.9 (d, J = 22.0 Hz), 16.1 (d, J = 23.0 Hz), 15.5 (d, J C18H14F2O [M+Na]+ = 307.0910, found = 307.0910.
= 22.0 Hz). 19F NMR (376 MHz, CDCl3): δ -178.8 (m), -179.6 (m).
HRMS (ESI) m/z calcd for C17H15FO[M+Na]+ = 277.1005, found = Substituted propargyl alcohol derivatives
277.1006.
Characterization data for tertiary propargyl alcohols
were prepared
1
using the literature procedure.18c
1-([1,1'-Biphenyl]-4-yl)-1,3-diphenylprop-2-yn-1-ol (1c).
2-(4-Bromophenyl)-1-fluorohept-3-yn-2-ol (4e).
The representative procedure was followed using 2-(4- Purification by column chromatography using ethyl
bromophenyl)hept-3-yn-2-ol 3e 75 mg, 0.280 mmol). acetate/hexanes (1/4). Yield 90% (1.25 g) from 3.87 mmol (1.0
Purification by column chromatography using ethyl g) of [1,1'-biphenyl]-4-yl(phenyl)methanone. Rf = 0.42 (1/5
acetate/hexanes (1/10) resulted in product 4e (48 mg, yield EtOAc/hexanes) Colourless solid 95-97 °C. IR (KBr, cm-1):
60%). Rf = 0.5 (1/5 EtOAc/hexanes). Colourless liquid. IR (neat, 3539, 2219, 1490, 1052, 843, 767. 1H NMR (400 MHz, CDCl3): δ
cm-1): 3418, 2958, 2246, 1489, 1089, 832; 1H NMR (400 MHz, 7.75-7.72 (m, 4H), 7.61-7.58 (m, 4H), 7.54-7.58 (m, 2H), 7.44-
(
,


CDCl3): δ 7.54-7.49 (m, 4H), 4.38 (dd, J = 47.2 Hz, 8.8 Hz, 1H), 7.39 (m, 3H), 7.37-7.29 (m, 6H), 2.9 (s, 1H). 13C NMR (100 MHz,
4.34 (dd, J = 48.0 Hz, 8.8 Hz, 1H), 2.85 (s, 1H), 2.27 (t, J = 7.2 CDCl3): δ 145.1, 144.2, 140.7, 131.9, 128.8, 128.5, 127.9, 127.5,
Hz, 2H), 1.63-1.56 (m, 2H), 1 (t, J = 7.2 Hz, 3H). 13C NMR (100 127.2, 126.6, 126.2, 122.5, 91.8, 87.4, 74.8. HRMS (ESI) m/z
MHz, CDCl3): δ 138.9, 131.6, 128.1, 122.7, 88.9 (d, J = 185.0 calcd for C27H20O[M+Na]+ = 383.1412, found = 383.1410.
Hz), 88.5, 79, 77.8 (d, J = 20.0 Hz), 21.9, 20.8, 13.6. 19F NMR 1-Phenyl-1,3-di-p-tolylprop-2-yn-1-ol (1h).
(376 MHz, CDCl3): δ (proton decoupled) -127.6, -127.7. HRMS Purification by column chromatography using ethyl
(ESI) m/z calcd for C13H14BrFO[M+Na]+ = 307.0110, found = acetate/hexanes (1/4). Yield 86% (1.36 g) from 5.10 mmol (1.0
307.0108.
g) of phenyl(p-tolyl)methanone. Rf = 0.5 (1/5 EtOAc/hexanes).
Colourless solid 72-74 °C. IR (KBr, cm-1):
3544, 2218, 1440,
1045, 826, 722. 1H NMR (400 MHz, CDCl3): δ 7.68-7.65 (m, 2H),
2-Fluoro-1-(phenylethynyl)-1,2,3,4-tetrahydronaphthalen-1-
ol (6).

The representative procedure was followed using 2-fluoro-1- 7.57-7.54 (m, 2H), 7.41-7.38 (m, 2H), 7.35-7.32 (m, 2H), 7.27-
(phenylethynyl)-1,2,3,4-tetrahydronaphthalen-1-ol ( , 75 mg, 7.26 (m, 1H), 7.15-7.12 (m, 4H), 2.87-2.84 (m, 1H), 2.35 (s, 3H),
0.302 mmol). Purification by column chromatography using 2.33 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 145.4, 142.5, 138.9,
5
ethyl acetate/hexanes (1/14) resulted in product
6
(66 mg, 137.5, 131.8, 129.2, 129.1, 128.4, 127.7, 126.1, 119.5, 91.3,
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J. Name., 2013, 00, 1-3 | 7
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87.3, 74.8, 21.6, 21.2. HRMS (ESI) m/z calcd for C23H20O[M+H]+ (d, J = 8.8 Hz, 2H), 7.45 (d, J = 8.8 Hz, 2H), 2.6 (s, 1H), 2.23 (t, J =
View Article Online
DOI: 10.1039/C7OB00140A
7.2 Hz, 2H), 1.69 (s, 3H), 1.58-1.53 (m, 2H), 0.99 (t, J = 7.2 Hz,
= 313.1592, found = 313.1591.
1-([1,1'-Biphenyl]-4-yl)-1-phenyl-3-(p-tolyl)prop-2-yn-1-ol (1i). 3H). 13C NMR (100 MHz, CDCl3): δ 145.4, 131.3, 126.9, 121.5,
Purification by column chromatography using ethyl 85.9, 83.6, 69.7, 33.7, 22.1, 20.7, 13.6. HRMS (ESI) m/z calcd
acetate/hexanes (1/4). Yield 88% (1.27 g) from 3.87 mmol (1.0 for C13H15BrO[M+Na]+ = 289.0204, found = 289.0200.
g) of [1,1'-biphenyl]-4-yl(phenyl)methanone. Rf = 0.54 (1/5
EtOAc/hexanes). Colourless solid 121-123 °C. IR (KBr, cm-1):

3550, 2213, 1484, 1045, 815, 760. 1H NMR (400 MHz, CDCl3): δ
7.75-7.71 (m, 4H), 7.57-7.56 (m, 4H), 7.43-7.27 (m, 8H), 7.14- Acknowledgements
7.13 (m, 2H), 2.98-2.92 (m, 1H), 2.35 (s, 3H). 13C NMR (100
MHz, CDCl3): δ 145.2, 144.3, 140.8, 140.6, 139, 131.8, 129.2, The authors thank SERB, India for funding this work. NN thank
128.8, 128.5, 127.8, 127.5, 127.3, 127.2, 126.6, 126.2, 119.4, Council of Scientific and Industrial Research (CSIR), India for
91.1, 87.6, 74.8, 21.6. HRMS (ESI) m/z calcd for fellowship.
C28H22O[M+Na]+ = 397.1568, found = 397.1569.
1-(4-Bromophenyl)-1-phenyl-3-(p-tolyl)prop-2-yn-1-ol (1j).
Purification by column chromatography using ethyl
acetate/hexanes (1/4). Yield 89% (1.26 g) from 3.83 mmol (1.0 References:
g) of (4-bromophenyl)(phenyl)methanone. Rf = 0.54 (1/5 1. (a) D. B. Harper and D. O’Hagan, Nat. Prod. Rep., 1994, 11
,
EtOAc/hexanes). Pale yellow solid 61-63 °C. IR (KBr, cm-1):

123; (b) G. W. Gribble, Progress in the Chemistry of
3364, 2218, 1478, 1051, 815, 700. 1H NMR (400 MHz, CDCl3): δ
7.62-7.59 (m, 2H), 7.49-7.47 (m, 2H), 7.38-7.34 (m, 4H), 7.28 (t,
J = 7.6 Hz, 2H), 7.23-7.22 (m, 1H), 7.07 (d, J = 7.6 Hz, 2H), 3.15
(s, 1H), 2.29 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 144.7, 144.3,
139.1, 131.7, 131.3, 129.2, 128.4, 127.9, 127.6, 126, 121.7,
Organic Natural Products Vol. 91 (eds Herz, W.; Kirby, G.
W.; Moore, R. E.; Steglich, W. &Tamm, C.) 1-498 (Springer,
1996). (e) Gribble, G. W.in Progress in the Chemistry of
Organic Natural Products Vol. 91 (eds Kinghord, A. D.;
Falk, H. & Kobayashi, J.); 1-613 (Springer, 2009).
119.1, 90.5, 87.8, 74.5, 21.6. HRMS (ESI) m/z calcd for 2. (a) K. Müller, C. Faeh and F. Diederich, Science, 2007, 317
,
C22H17BrO [M+Na]+ = 399.0360, found = 399.0362.
1881; (b) S. Purser, P. R. Moore, S. Swallow and V.
Gouverneur, Chem. Soc. Rev., 2008, 37, 320; (c) R. Filler
and R. Saha, Future Med. Chem., 2009, , 777; (d) D.
O’Hagan, Chem. Soc. Rev., 2008, 37, 308; (e) J. Wang, M.
Sꢀnchez-Rosellꢁ, J. L. Aceꢂa, C. del Pozo, A. E. Sorochinsky,
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114, 2432; (f) E. P. Gillis, K. J. Eastman, M. D. Hill, D. J.
1-([1,1'-Biphenyl]-4-yl)-1-phenylhex-2-yn-1-ol (1k).
Purification by column chromatography using ethyl
acetate/hexanes (1/4). Yield 80% (1.01 g) from 3.87 mmol (1.0
g) of [1,1'-biphenyl]-4-yl(phenyl)methanone. Rf = 0.58 (1/5
1
EtOAc/hexanes). Colourless solid m.p. 60-62 °C. IR (KBr, cm-1):
1

3435, 2958, 2235, 1490, 1008, 827, 761. H NMR (400 MHz,
CDCl3): δ 7.69-7.64 (m, 4H), 7.58-7.53 (m, 4H), 7.44-7.39 (m,
2H), 7.36-7.32 (m, 3H), 7.28-7.24 (m, 1H), 2.76-2.75 (m, 1H),
2.36-2.32 (m, 2H), 1.67-1.60 (m, 2H), 1.06-1.02 (m, 3H). 13C
NMR (100 MHz, CDCl3): δ 145.6, 144.7, 140.8, 140.5, 128.8,
128.3, 127.7, 127.4, 127.2, 127.1, 126.6, 126.1, 88.4, 83.3,
Donnelly and N. A. Meanwell, J. Med. Chem., 2015, 58
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D. Banner, S. Bendels, M. Kansy, B. Kuhn, K. Müller, U.
Obst-Sander and M. Stahl, ChemBioChem., 2004, , 637.
,
6
5
5
74.5, 22.2, 21.1, 13.8. HRMS (ESI) m/z calcd for C24H22O[M+H]+ 3. (a) D. O’Hagan, J. Fluorine Chem., 2010, 131, 1071; (b) L.
= 327.1749, found = 327.1750.
Hunter, Beilstein J Org Chem., 2010, 6, 38; (c) T. Furuya, C.
1-Phenyl-1-(p-tolyl)hex-2-yn-1-ol (1l).
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2008, 11, 803; (d) B. K. Park, N. R. Kitteringham and P. M.
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B. E. Smart, J. Fluorine Chem., 2001, 109, 3.
Purification by column chromatography using ethyl
acetate/hexanes (1/4). Yield 76% (1.02 g) from 5.10 mmol (1.0
g) of phenyl(p-tolyl)methanone. Rf = 0.35 (1/5 EtOAc/hexanes).
Pale yellow liquid. IR (neat , cm-1):
 3457, 2969, 2229, 1445, 4. (a) S. M. Ametamey, M. Honer and P. A. Schubiger, Chem.
1002, 815, 749. 1H NMR (400 MHz, CDCl3): δ 7.63-7.57 (m, 2H),
7.51-7.46 (m, 2H), 7.32-7.26 (m, 2H), 7.24-7.21 (m, 1H), 7.13-
7.08 (m, 2H), 2.81-2.74 (m, 1H), 2.31-2.27 (m, 5H), 1.64-1.56
(m, 2H), 1.06-0.98 (m, 3H). 13C NMR (100 MHz, CDCl3): δ 145.8,
142.8, 137.2, 128.9, 128.2, 127.4, 126.1, 87.9, 83.5, 74.4, 22.2,
Rev., 2008, 108, 1501; (b) M. E. Phelps, Proc. Natl. Acad.
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2-(4-Bromophenyl)hept-3-yn-2-ol (3e).
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2014, 1, 712; (d) J. Wu, Tetrahedron Lett., 2014, 55, 4289;
ethylacetate/hexanes (1/4): Yield 72% (0.71 g) from 3.74 mmol
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
0.45 (1/5
3386, 2957,
EtOAc/hexanes). Colourless oil. IR (neat, cm-1).
1
2246, 1495, 1013, 827, 723. H NMR (400 MHz, CDCl3): δ 7.51
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8 | J. Name., 2012, 00, 1-3
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references therein (d) Y.-F. Qiu, X.-R. Song, M. Li, X.-Y. Zhu,
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DOI: 10.1039/C7OB00140A
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