AgII-Mediated Synthesis of β-Fluoroketones by Oxidative Cyclopropanol Opening

Article abstract of DOI:10.1002/ejoc.201700899

A regioselective synthesis of β-fluorinated ketones by silver(II)-mediated ring opening is described. Commercially available AgF₂ serves as both an oxidant and fluorine-atom source. A variety of β-fluorinated ketones are efficiently prepared from tertiary cyclopropanol precursors, offering a straightforward approach for the introduction of a fluorine atom at a remote site. Selectivity is observed in the site of bond cleavage, which leads to fluorination at the more substituted site. A radical mediated sequential homolytic C–C bond cleavage and C–F bond formation is suggested.

Full text of DOI:10.1002/ejoc.201700899

A Journal of
Accepted Article
Title: Ag(II)-Mediated Synthesis of β-Fluoroketones via Oxidative
Cyclopropanol Opening
Authors: Yuanlin Deng, Nabeelah I. Kauser, Shahidul M Islam, and
Justin T. Mohr
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201700899
Link to VoR: http://dx.doi.org/10.1002/ejoc.201700899
Supported by

European Journal of Organic Chemistry
10.1002/ejoc.201700899
FULL PAPER
Ag(II)-Mediated Synthesis of β-Fluoroketones via Oxidative
Cyclopropanol Opening
Yuanlin Deng, Nabeelah I. Kauser, Shahidul M. Islam, and Justin T. Mohr*
Abstract: A regioselective synthesis of β-fluorinated ketones via
silver(II)-mediated ring opening is described. Commercially
available AgF serves as both an oxidant and fluorine atom source.
A variety of β-fluorinated ketones are efficiently prepared from
tertiary cyclopropanol precursors, offering straightforward
Results and Discussion
2
2
To explore the potential of AgF , we selected a strain-based
[
8 ]
strategy
substrates.
for remote fluorination using cyclopropanols as
[
9]
[10a]
[10b]
a
Some recent reports from Zhu,
Murakami,
[
10c]
approach for the introduction of a fluorine atom at a remote site.
Selectivity is observed in the site of bond cleavage leading to
and Loh,
have found this type of transformation feasible with
Ag(I) in the presence of superstoichiometric quantities of
®
fluorination at the more substituted site.
A radical mediated
Selectfluor as an electrophilic source of F (and perhaps also as
[
10d]
sequential homolytic C–C bond cleavage and C–F bond formation is
suggested.
an oxidant). Lectka
on photoredox catalysis in the presence of Selectfluor . Related
has developed a related system based
®
[11]
[12]
halogenative transformations using Mn
and Ag, as well as
bond forming protocols based on Cu
catalysts corroborate the versatility of cyclopropanols for a
[
13 ]
[ 14 ]
C–C
and C–N
Introduction
[15]
variety of metal-mediated transformations.
We hoped that the
presumably different reactivity of Ag(II) might facilitate either a
distinctive reaction pathway or expand the scope of the
transformations reported previously.
The synthesis of organofluorine compounds remains
a
[1]
significant and important challenge in organic chemistry.
The
importance of fluorine in a range of pharmaceutical compounds
particularly highlights the demand for novel methods for forging
With cyclopropanols readily available via the Kulinkovich
[
16 ]
protocol,
we commenced our study using AgF
2
and
[
2]
new C–F bonds.
Especially useful are fluorination reactions
cyclopropanol 1a as a model substrate (Table 1). We were
pleased to find that a ring opening/fluorination cascade occurred
readily to deliver the β-fluoroketone in fair yield as a single
constitutional isomer, suggesting site selectivity in the putative
C–C bond scission. Other fluoride salts such as AgF or alkali
metal fluorides did not lead to fluorinated products under similar
[
1e]
that install the new fluorine atom at a relatively remote site.
Hand-in-hand with the pervasive reactivity concerns of
fluorinating agents are issues of reagent cost and safe handling.
This is a particular challenge for electrophilic F sources since
these are frequently synthesized from highly reactive molecular
[
3]
[4]
fluorine and the resulting reagents are often strong oxidants.
conditions, and high-valent transition metal fluorides MnF
CoF led to nonspecific decomposition. To optimize the reaction
protocol we first examined the time of reaction, which proved a
3
and
However, the oxidizing ability may also be viewed as an
opportunity for cascade reactivity toward organofluorine
compounds.
3
[
a]
Table 1. Optimization of reaction conditions.
One convenient, commercially available source of
[
5]
electrophilic F is AgF
solid compares favorably to other common sources of
electrophilic F on a cost basis. For instance, at present AgF
$110 for 10 g = $1.60 per mmol, Alfa Aesar) is nearly 20% less
costly than the more common 1,4-diazoniabicyclo[2.2.2]octane
2
.
This relatively low molecular weight
HO
F
O
R
AgF2
2
R
(
ClCH2CH2Cl
inital T → 22 °C
1
2
®
[4j]
bis(tetrafluoroborate) (Selectfluor ) reagent ($135 for 25 g =
Entry
Substrate
AgF2
[equiv]
Initial T
[°C]
Time at
initial T [h] 22 °C [h]
Time at
Yield of 2
[%]
$
1.91 per mmol, Alfa Aesar) and nearly 50% less than N-
[
4g]
fluorobenzenesulfonimide (NFSI)
($251 for 25 g = $3.17 per
1
2
3
4
5
6
7
8
9
1a (R = Me)
2
2
2
2
2
2
2
2
1
4
2
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
4
60
60
64
57
42
31
44
51
25
24
53
mmol, Alfa Aesar). An additional practical advantage of a Ag
salt is that the byproducts may also serve to scavenge any HF
produced during the reaction and therefore substantially reduce
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
6
8
17
4
[
5]
potential safety hazards or pH changes. In the context of our
–40
[
6]
broader program exploring remote functionalization reactions
–40
–40
–40
–40
–15
8
[
7]
17
17
17
1
and halogenation protocols, we were particularly intrigued by
the AgF reagent that combines the potential to not only supply
2
1
0
an electrophilic F, but also behave as a potent oxidant that could
expand the scope of fluorination protocols.
11
12[b] 1b (R = i-Pr)
2
2
2
2
0
0
1
2
2
1
1
2
1
1
58
62
48
72
1 [
b]
3
1b
14[b] 1b
15[b] 1b
0
[*]
Y. Deng, N. I. Kauser, Prof. Dr. S. M. Islam, Prof. Dr. J. T. Mohr
Department of Chemistry, University of Illinois at Chicago
–15
845 West Taylor Street
Chicago, Illinois 60607, United States
E-mail: jtmohr@uic.edu
[a] Reactions performed with 0.1 mmol of substrate 1 in ClCH
CH
2
Cl (2 mL).
2
1
9
Yields were determined by F NMR using α,α,α-trifluorotoluene as an internal
http://www2.chem.uic.edu/mohr/
Supporting information for this article is given via a link at the end of
the document.
standard. [b] Reaction performed with 0.3 mmol of substrate 1 in ClCH
2
CH Cl
2
(6 mL).
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European Journal of Organic Chemistry
10.1002/ejoc.201700899
FULL PAPER
complex issue. Under our preliminary conditions the yield of
fluoroketone increased only moderately over time, but
decreased at extended reaction time (entries 1–5). Conducting
the reaction at an initial temperature of –40 °C required long
reaction times after warming to ambient temperature to obtain
comparable yields (entries 6–8). Either increasing or decreasing
[a]
Table 2. Ring-opening/fluorination of cyclopropanols.
HO
R2
F
O
AgF2 (2 equiv)
ClCH CH Cl
R1
R1
R2
2
2
1
–15 → 22 °C
2
2
the quantity of AgF under these conditions was detrimental to
Entry
1
Substrate
HO
Product
Yield [%]
the reaction (entries 8–10). A compromise was found by
conducting the reaction at an initial temperature of –15 °C,
leading to 53% yield of β-fluoroketone in 2 h overall (entry 11).
Concurrently, we had observed that notably higher yield was
obtained with substrate 1b and we therefore validated our
observations using this substrate, again finding the –15 °C initial
F
O
1a
1b
2a 53 (51)
2b 72 (69)
HO
HO
F
F
O
[17]
2
temperature condition to be optimal (entries 12–15).
With effective ring-opening conditions identified we next
turned to examination of the scope of the reaction (Table 2).
Increasing the steric bulk adjacent to the hydroxyl group did not
O
O
3
4
5
6
7
1c
1d
1e
1f
2c 59
adversely affect the reaction (entries 1–3).
An aromatic
substituent attached to the carbinol increased reaction efficiency
substantially, however (entry 4). Substrates containing p-tolyl
substituents (entries 5–7) led to mono-fluorinated products
exclusively, suggesting that under the reaction conditions a
simple benzylic fluorination mechanism is not likely and the site
of fluorination is dependent on the ring-opening process.
Encouraged by this result, we examined substrates where
fluorination would occur at a non-benzylic site (entries 9–10).
Products of ring-opening/fluorination were observed in these
cases with no evidence of fluorination at other sites, although
yields were somewhat reduced.
HO
Ph
F
2d 93
Ph
HO
F
O
2e 47
HO
HO
F
O
2f 71 (55)
2g 67 (47)
Purification of the fluoroketone products was complicated by
the presence of α,β-unsaturated ketone in some cases. This
contaminant exhibited similar chromatographic properties to the
fluoroketone and care is needed to effectively separate the
F
O
Ph
Ph
1g
HO
HO
F
O
1
desired product. The enone is observable in H NMR analysis of
8
1h
2h 90
crude reaction mixtures and the desired fluoroketone is stable
t-Bu
under chromatographic conditions on SiO
2
. Isolated enone does
t-Bu
not convert to β-fluoroketone under the reaction conditions.
Although it is attractive to suggest that this conjugated
compound arises from elimination HF from the fluoroketone, in
control experiments we have not observed conversion of the
fluoroketone to enone under typical reaction conditions.
Together these observations suggest that enone likely arises
F
O
Ph
9
1i
2i 60
Ph
Et
HO
Et
Ph
F
O
1
0
1j
2j 39 (42)
Ph
[
a] Reactions were performed with 0.3 mmol of substrate 1 and AgF
2
(2 equiv)
from
a competing reaction pathway perhaps involving a
1
9
in ClCH
2
CH
2
Cl (9 mL) for 2 h. Yields determined by F NMR using α,α,α-
mechanistic intermediate en route to the fluoroketone.
trifluorotoluene as an internal standard. Values in parentheses are isolated
yields after chromatography.
Polar functional groups within the molecule pose a challenge
both to substrate preparation via the Kulinkovich protocol. To
study the effect of diverse functional groups in our Ag-mediated
[
19]
transformation are ongoing.
[
18]
Given the apparent improvement in reaction efficiency with
aryl carbinols relative to aliphatic carbinols, we carried out a
competition experiment to gain insight into the process and
reaction, we carried out a “robustness” study using a standard
cyclopropanol and various additives (Table 3). The results show
a limited scope of tolerated functional groups containing Lewis
basic atoms. This could be due to strong Lewis acid–Lewis
base interactions with the Ag center or possibly oxidation by the
Ag. Some functional groups impede the ring-opening reaction
moderately but are consumed in the course of the reaction.
Others, such as an alkyne, cause a dramatic decrease in yield
but survive the reaction largely intact. Further studies to
understand these effects and expand the scope of this
perhaps provide mechanistic insight (Scheme 1).
In
experiments with either 1 or 2 equiv of AgF the benzylic alcohol
2
outcompeted the aliphatic tertiary alcohol by a factor of ~4–5-
fold. This is important in demonstrating that the improvement in
efficiency with aryl carbinols is due, at least in part, to an
increase in rate and not some undetermined factor such as
product stability.
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European Journal of Organic Chemistry
10.1002/ejoc.201700899
FULL PAPER
F
[
a]
Table 3. Robustness study.
Ag
HO
O
O
R2
AgF2
–HF
R2
R2
B
R1
R1
–AgF
R1
HO
AgF2 (2 equiv)
additive (1 equiv)
ligand
exchange
bond
homolysis
F
O
A
ring
fission
ClCH2CH2Cl
1
b
–15 → 22 °C
2b
F
O
F
Ag
F
O
Entry Additive
Yield Recovered Entry Additive
Yield Recovered
R1
R2
–AgF
2
b
Additive
[%]
2b
Additive
[%]
R1
R2
[%]
[%]
F-atom
abstraction
C
5
29
87
1
none
72
–
Ph
Ph
EtO2C
Scheme 2. Mechanistic hypothesis for ring opening/fluorination.
2
3
4
OH 53
23
18
3
6
7
8
O
46
8
5
t-Bu
C
N
57
39
Ph
N
95
56
release in the cyclopropane system leading to C-centered
N
pyridine
33
radical intermediate C. This step could account for the to form
Ag–alkoxide complex
A
could be followed by single
[
a] See Table 2 for reaction conditions. Yields determined by NMR.
regioselectivity in fragmentation due to a preference for the
formation of the secondary radical intermediate. Finally, F-atom
Although there are several plausible explanations for this
2
abstraction from a second molecule of AgF would lead to the β-
difference in reactivity, the effect is likely best explained through
an influence at an early stage of the mechanism. Whereas the
aryl group proximal to the oxygen would likely stabilize a
fluoroketone product and account for the optimal reaction
stoichiometry. The AgF and HF byproducts likely combine to
2
form silver bifluoride (AgHF ) mitigating changes in acidity.
hypothetical O-centered or benzylic radical, an aryl group at this
site would be expected to accelerate a mechanism involving
single electron intermediates that could arise from oxidation or
bond fission. To estimate the influence of the neighboring aryl
group we referred to the bond dissociation energy (BDE) of t-
Although oxidation of the intermediate radical C to the
corresponding carbocation is also possible in the presence of
Ag(II), we do not believe this to be the major pathway to the
fluorinated products since we predict deprotonation to be more
likely in this case to generate the undesired enone products that
are observed in some cases. Potential radical inhibitors or
BuO–Ot-Bu (162.8 ± 2.1 kJ/mol) and Ph
3
CO–OCPh
3
(131.4
[
20 ]
kJ/mol).
The significantly weaker bond in the arylated
3
trapping agents such as TEMPO, BHT, and Ph CCl all negate
peroxide may suggest a preference for a radical adjacent to the
aromatic rings as a potential explanation for the increase rate in
fluorination under our typical conditions, but the corresponding
enone is observed in low yields with TEMPO or BHT. These
experiments are consistent with a radical-based mechanism of
C–F bond formation, but are not definitive. However, the
observation of the enone under these conditions could be
explained by either oxidation of the putative radical or trapping to
form a β-heteroatom-containing intermediate that could undergo
elimination to generate the conjugated system.
[21]
our competition experiment.
Alternatively, the inductive effect of the aryl ring could
facilitate the formation of a Ag–O interaction by increasing
acidity of the hydroxyl group. To substantiate this possibility, we
conducted theoretical calculations of the aqueous pK
a
of the
Using either an implicit
solvation model or an implicit solvation model with explicit water
molecules, the same trend is observed: the computed pK of 1d
is approximately two pK units lower than that of 1b, which
[
22]
alcohol moieties is both 1b and 1d.
An alternative homoenolate-type mechanism involving a
carbanion intermediate would appear at odds with observed the
preference for opening at the secondary carbon site as this
anion is predicted to be higher in energy than the alternative
a
a
would be consistent with an increased rate of Ag–O coordination.
A potential mechanism for the fragmentation is shown in
Scheme 2. Related processes have invoked Ag(III) as a key
primary anion. An electrophilic mechanism initiated by a formal
+
[
10]
F
interacting with the cyclopropane would similarly contradict
reactive intermediate, although we predict that Ag(II) may be a
viable promoter of fragmentation. Thus, initial ligand exchange
electron oxidation via Ag–O bond homolysis. The resulting
alkoxy radical B could undergo bond fission driven by strain
the empirical preference for introducing the F at the more
substituted site due to expected steric interactions. We have
noted that the cyclopropanol substrates are sensitive to strong
base leading to mixtures with substantial quantities of
nonfluorinated ketones even in the presence of fluorinating
agents. Further mechanistic studies to elucidate the details of
the mechanism are ongoing in our laboratories.
HO
HO
AgF2
F
O
F
O
Ph
Ph
Ph
Ph
Ph
Ph
ClCH CH Cl
2
2
–
15 → 22 °C
1
b
1d
2b
5%
15%
2d
(
1 equiv each)
1
2
equiv AgF2:
26%
56%
Conclusions
equiv AgF2:
In conclusion, we have developed a protocol for the synthesis of
Scheme 1. Competition experiment between alkyl- and arylcarbinols.
β-fluoroketones using readily available cyclopropanols as
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European Journal of Organic Chemistry
10.1002/ejoc.201700899
FULL PAPER
precursors. The transformation features the use of commercially
aluminum foil, and stirred for 1 h. The reaction mixture was passed
through a short silica plug to remove the solid residue, eluting with
available AgF
Regioselectivity in the putative bond fission step enables
selective generation of secondary organofluorides. The
2
as both an oxidant and a source of F.
2 2 2 2
CH Cl (2 x 1 mL). The vial was rinsed with CH Cl (2 x 3 mL). The
resulting organic solution was concentrated in vacuo. Neat α,α,α-
trifluorotoluene (12.0 µL) was added to the residue as an internal
transformation is relatively insensitive to sterics and the
presence of aryl groups affixed to the carbinol center appear to
accelerate the reaction suggesting an influence of inductive
withdrawing groups of resonance stabilizing groups.
Applications of this methodology in the synthesis of valuable
fluorinated target molecules are underway.
19
standard and a F NMR spectrum was obtained to determine the yield.
(
The residue was purified by flash chromatography on silica gel to afford
the desired product.)
Specific quantities of reagents, procedural variations, and purification
conditions may be found below in the entry containing the
characterization data.
2
Procedure for Retreatment of Product Mixture with AgF : An oven-
Experimental Section
dried 20 mL plastic vial equipped with a magnetic stir bar, was evacuated
and backfilled with nitrogen in a glovebox antechamber (three cycles). In
General Methods: Unless otherwise stated, reactions were performed
the glovebox, solid AgF
the vial was then sealed with a rubber septum and transferred out of the
glovebox. The vial was connected to a N -filled Schlenk line and then
charged with anhydrous 1,2-dichloroethane (0.84 mL) via syringe. The
suspension was cooled to –15 °C and stirred vigorously for 1 min.
solution comprising a 3.9:1 ratio of 3-fluoro-1,3-diphenylpropan-1-one
2
(24.5 mg, 0.168 mmol, 2 equiv) was added and
in oven-dried 20 mL plastic vials under a N
deoxygenated solvents. Silver difluoride was purchased from Alfa Aesar
and stored in a N -filled glovebox. Anhydrous 1,2-dichloroethane was
purchased from Macron, distilled over CaH , followed by three freeze-
pump-thaw degassing cycles. Starting materials were synthesized
2
atmosphere using dry,
2
2
2
A
[
16c]
according to reported literature.
Deuterated chloroform (CDCl
3
,
1
(
15.5 mg, 0.0679 mmol, quantity determined by H NMR) and (E)-
9
9.9%, extra dry) was purchased from Cambridge Isotope Laboratories,
1
chalcone (3.6 mg, 0.0173 mmol, quantity determined by H NMR)
dissolved in anhydrous 1,2-dichloroethane (1.68 mL) was added in one
Inc. and was used without further purification. Reaction temperatures
were controlled by an IKAmag immersion temperature modulator. Thin-
layer chromatography (TLC) was performed using Silicycle silica gel 60
F254 precoated plates (0.25 mm) and visualized by UV fluorescence
portion to AgF
5 °C. The mixture was warmed to 23 °C, wrapped with aluminum foil,
and then stirred for 1 h. The reaction mixture was passed through a
short silica gel plug to remove the solid residue and eluted with CH Cl (2
x 1 mL). The vial was washed with CH Cl (2 x 3 mL). The resulting
organic solution was concentrated in vacuo. Neat α,α,α-trifluorotoluene
2
suspension and the mixture was then stirred for 1 h at –
1
quenching or staining with p-anisaldehyde solutions.
Flash
[
23]
2
2
chromatography
was performed using Silicycle SiliaFlashR P60 silica
2
2
gel (40–63 µm particle size). Melting points were determined using a
Mel-Temp electrothermal capillary melting point apparatus and the
19
(
12.0 µL) was added to the residue as internal standard and a F NMR
1
13
values reported are uncorrected.
recorded on Bruker Avance DRX-500 (at 500 and 126 MHz,
respectively) or DPX-400 instrument (at 400 and 101 MHz, respectively)
H
and
C NMR spectra were
spectrum was obtained to determine the yields. The residue was purified
by flash chromatography (10:1 hexanes/acetone) on silica gel to afford a
a
8
.6:1 mixture of fluoroketone and enone (16.6 mg total: 3-fluoro-1,3-
1
and are reported relative to Me
reported as follows: chemical shift (δ ppm) (multiplicity, coupling constant
Hz), integration). Multiplicities are reported as follows: s = singlet, d =
doublet, t = triplet, q = quartet, quin = quintet, sept = septet, m = multiplet,
4
Si (δ 0.0). Data for H NMR spectra are
diphenylpropan-1-one 14.1 mg, 0.0618 mmol and (E)-chalcone 1.5 mg,
1
0
.0072 mmol, determined by H NMR).
(
1
3
Procedure for Competition Experiments: An oven-dried 20 mL plastic
vial equipped with a magnetic stir bar, was evacuated and backfilled with
nitrogen in a glovebox antechamber (three cycles). In the glovebox, solid
app. = apparent, br s = broad singlet. Data for C NMR spectra are
1
9
reported in terms of chemical shift relative to Me
4
Si (δ 0.0).
F NMR
spectra were recorded on a Bruker Avance DRX-400 at 376 MHz and are
reported relative to the internal standard α,α,α-trifluorotoluene (δ –63.1
ppm). Infrared (IR) spectra were recorded on a Nicolet iS5 FTIR
AgF
sealed with a rubber septum and transferred out of the glovebox. The
vial was connected to a N -filled Schlenk line and then charged with
2
(14.6 mg, 0.1 mmol, 1 equiv) was added and the vial was then
–
1
2
spectrometer and are reported in frequency of absorption (cm ). GC/MS
anhydrous 1,2-dichloroethane (3 mL) via syringe. The suspension was
cooled to –15 °C and stirred vigorously for 1 min. A solution of 1-
isopropyl-2-phenylcyclopropan-1-ol (17.6 mg, 0.1 mmol, 1 equiv) and
analyses were performed on
chromatograph interfaced to
a
Hewlett Packard Model 6890 gas
Hewlett Packard Model 5973 mass
a
selective detector (15 m x 0.25 mm capillary column, HP-5MS). High-
resolution mass spectra (HRMS) were obtained from the University of
Illinois at Urbana–Champaign Mass Spectral Facility. All the electronic
1
1
,2-diphenylcyclopropan-1-ol (21.0 mg, 0.1 mmol, 1 equiv) dissolved in
,2-dichloroethane (1 mL) was added at once and then the mixture was
[
24
]
stirred for 1 h at –15 °C. The suspension was warmed to 23 °C, wrapped
with aluminum foil, and stirred for 1 h. The reaction mixture was passed
structure calculations were carried out with Gaussian09
Supporting Information for details).
(see
through a short plug of SiO
2
to remove the solid residue and eluted with
Cl (2 x 3 mL).
CH Cl (2 x 1 mL) and then the vial was washed with CH
2
2
2
2
General Procedure for Ring-Opening Fluorination: An oven-dried 20
mL plastic vial equipped with a magnetic stir bar, was evacuated and
backfilled with nitrogen in a glovebox antechamber (three cycles). In the
The combined solution was concentrated in vacuo. Neat α,α,α-
trifluorotoluene (12.0 µL) was added into the residue as an internal
19
standard and F NMR spectrum was obtained to determine the yield.
glovebox, solid AgF
vial was then sealed with a rubber septum and transferred out of the
glovebox. The vial was connected to a N -filled Schlenk line and then
2
(87.6 mg, 0.6 mmol, 2 equiv) was added and the
(
The residue was purified by flash chromatography on silica gel to afford
the desired product.) The experiment was also carried out with 0.2 mmol
of AgF (29.2 mg, 2 equiv) in a similar manner.
2
2
charged with anhydrous 1,2-dichloroethane (3 mL). The mixture was
cooled to –15 °C and stirred vigorously for 1 min. A solution of
cyclopropanol (0.05 M soln in 1,2-dichloroethane, 6 mL, 0.3 mmol, 1
equiv) was added in one portion and the resulting suspension was stirred
for 1 h at –15 °C. The mixture was warmed to 23 °C, wrapped with
Procedure for Robustness Study: An oven-dried 20 mL plastic vial
equipped with a magnetic stir bar, was evacuated and backfilled with
nitrogen in a glovebox antechamber (three cycles). In the glovebox, solid
2
AgF (87.6 mg, 0.6 mmol, 2 equiv) was added and the vial was then
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European Journal of Organic Chemistry
10.1002/ejoc.201700899
FULL PAPER
sealed with a rubber septum and transferred out of the glovebox. The
7.19 (d, J = 8.0 Hz, 2H), 2.44 (dd, J = 10.5, 8.0 Hz, 1H), 1.30 (s, 10H),
1
3
vial was connected to a N
2
-filled Schlenk line and then charged with
1.03 (dd, J = 10.5, 6.0 Hz, 1H), 0.81 (s, 9H); C NMR (126 MHz, CDCl
3
)
anhydrous 1,2-dichloroethane (3 mL). The mixture was cooled to –15 °C
and stirred vigorously for 1 min. A solution of cyclopropanol (0.05 M soln
in 1,2-dichloroethane, 6 mL, 0.3 mmol, 1 equiv) and a specific additive
δ 148.9, 135.0, 129.2, 124.8, 35.2, 31.7, 31.4, 31.3, 31.2, 26.9, 14.1; IR
–
1
(neat) 3366, 2956, 2904, 2869, 1515, 1362, 820, 611, 526 cm ; GC/MS
(m/z): 246.1 (30%), 189.0 (26%), 175.1 (19%), 147.1 (100%), 133.0
(96%), 117.0 (19%), 91.0 (17%), 57.0 (82 %).
(
0.3 mmol,
suspension was stirred for 1 h at –15 °C. The mixture was warmed to
3 °C, wrapped with aluminum foil, and stirred for 1 h. The reaction
mixture was passed through a short silica plug to remove the solid
residue, eluting with CH Cl (2 x 1 mL). The vial was rinsed with CH Cl
2 x 3 mL). The resulting organic solution was concentrated in vacuo.
Neat α,α,α-trifluorotoluene (12.0 µL) and dibromomethane (7.0 µL) were
1 equiv) was added in one portion and the resulting
2
2
2
-Benzyl-1-phenylcyclopropan-1-ol (1i): Clear colorless liquid; TLC (SiO )
1
R
f
= 0.43 in 5:1 hexanes/acetone, p-anisaldehyde stain; H NMR (500
MHz, CDCl ) δ 7.45 (d, J = 7.0 Hz, 2H), 7.37 (t, J = 7.5 Hz, 2H), 7.31 (t, J
8.0 Hz, 1H), 7.24 (t, J = 8.0 Hz, 2H), 7.16 (t, J = 7.0 Hz, 1H), 7.07 (d, J
2
2
2
2
3
(
=
=
8.0 Hz, 2H), 2.53 (dd, J = 15.0, 2.5 Hz, 1H), 2.31 (s, 1H), 2.08 (dd, J =
1
19
added to the residue as internal standards. H and F NMR spectra were
obtained to determine the yield and the quantity of remaining additive.
1
5.0, 8.0 Hz, 1H), 1,82–1.75 (m, 1H), 1.25 (dd, J = 10.0, 6.0 Hz, 1H),
13
1
3
.14 (app. t, J = 6.5 Hz, 1H); C NMR (126 MHz, CDCl ) δ 141.1, 140.0,
1
28.3, 128.2, 128.1, 127.6, 125.8, 61.8, 35.2, 27.8, 18.6; IR (neat) 3314,
–
1
Experimental Data for Cyclopropanols and β-Fluoroketones:
3060, 3027, 2920, 2852, 1600, 1492, 1450, 1190, 1060, 764, 692 cm ;
Substrates were synthesized via the method previously reported by Cha
GC/MS (m/z): 224.1 (24%), 209.0 (4%), 133.0 (48%), 120.0 (46%), 105.0
[
16c]
and co-workers.
Based on the spectra obtained using this method, all
(100%), 91.1 (30%), 77.0 (49%).
the substrates are single diastereomers and the relative configurations
were assigned by analogy to the Cha work. Spectra for cyclopropanols
2
-(4-Ethylbenzyl)-1-phenylcyclopropan-1-ol (1j): Clear colorless liquid;
[
25]
[26]
[25c]
[10d]
1
a, 1d, 1e
and 2a
matched those in the literature.
1
TLC (SiO
2
) R
f
= 0.46 in 5:1 hexanes/acetone, p-anisaldehyde stain;
H
NMR (500 MHz, CDCl
3
) δ 7.45 (d, J = 7.5 Hz, 2H), 7.37 (t, J = 7.0 Hz,
1
-Isopropyl-2-phenylcyclopropan-1-ol (1b): White powder; mp 60–62 °C;
2H), 7.31 (t, J = 7.5 Hz, 1H), 7.08 (d, J = 8.0 Hz, 2H), 6.99 (d, J = 8.0 Hz,
2H), 2.60 (q, J = 8.0 Hz, 2H), 2.52 (dd, J = 15.0, 6.5 Hz, 1H), 2.02 (dd, J
= 15.0, 8.0 Hz, 1H), 1.81–1.72 (m, 1H), 1.25 (app. t, J = 5.5 Hz, 1H), 1.22
1
TLC (SiO
2
) R
f
= 0.33 in 5:1 hexanes/acetone, p-anisaldehyde stain;
) δ 7.30–7.24 (m, 2H), 7.21–7.14 (m, 3H), 2,43
dd, J = 9.5, 7.5 Hz, 1H), 1.24–1.11 (m, 3H), 1.03 (d, J = 6.5 Hz, 3H),
H
NMR (500 MHz, CDCl
3
1
3
(
(app. t, J = 7.5 Hz, 3H), 1.12 (app. t, J = 6.5 Hz, 1H); C NMR (126 MHz,
CDCl ) δ 141.7, 140.1, 138.3, 128.3, 128.1, 128.1, 127.7, 127.6, 61.9,
1
3
0
1
1
1
.77 (d, J = 6.5 Hz, 3H); C NMR (126 MHz, CDCl
28.0, 125.8, 64.9, 31.9, 30.1, 18.5, 17.6, 16.7; IR (neat) 3369, 2968,
3
) δ 138.0, 128.3,
3
34.8, 28.4, 28.0, 18.6, 15.6; IR (neat) 3336, 2963, 2930, 2859, 1682,
–
1
–1
600, 1450, 1216, 1047, 777, 702 cm ; GC/MS (m/z): 176.1 (16%),
1512, 1447, 1190, 1060, 1024, 836, 758, 699 cm ; GC/MS (m/z): 252.1
31.0 (68%), 105.0 (100%), 91.0 (72%), 77.0 (32%).
(27%), 237.0 (11%), 132.1 (58%), 119.0 (44%), 105.0 (100%), 91.1
(
23%), 77.0 (44%).
1
-(tert-Butyl)-2-phenylcyclopropan-1-ol (1c): White powder; mp 58–
5
9 °C; TLC (SiO
2
) R
f
= 0.37 in 5:1 hexanes/acetone, p-anisaldehyde
) δ 7.30–7.22 (m, 4H), 7.20–7.15 (m, 1H),
.49 (dd, J = 10.0, 8.0 Hz, 1H), 1.33 (dd, J = 8.0, 6.0 Hz, 1H), 1.06 (dd, J
4-fluoro-4-phenylbutan-2-one (2a): The title compound was prepared with
1
19
stain; H NMR (500 MHz, CDCl
3
a
F NMR yield of 53%, and was isolated (25.2 mg, 51%). Spectral data
[
10d]
2
=
1
3
matches with the reported data.
1
3
10.0, 8.0 Hz, 1H), 0.80 (s, 9H); C NMR (126 MHz, CDCl
3
) δ 138.0,
28.3, 128.0, 125.8, 64.9, 31.9, 30.1, 18.5, 17.6, 16.7; IR (neat) 3473,
1
-fluoro-4-methyl-1-phenylpentan-3-one (2b): The title compound was
–
1
357, 2959, 1599, 1493, 1362, 1187, 1145, 774, 696, 608 cm ; GC/MS
19
prepared with
a
1
F NMR yield of 72% containing 10% enone
(
m/z): 190.1 (6%), 133.0 (65%), 105.1 (100%), 91.0 (66%), 77.0 (19%),
(
determined by H NMR) and was isolated as a pale yellow liquid (40.2
mg, 69%). TLC (SiO ) R = 0.52 in 5:1 hexanes/acetone, p-anisaldehyde
stain; H NMR (500 MHz, CDCl ) δ 7.42–7.31 (m, 5H), 5.99 (ddd, J =
5
7.1 (57%).
2
f
1
3
1
-(tert-Butyl)-2-(p-tolyl)cyclopropan-1-ol (1f): White powder; mp 64–
46.5, 8.5, 4.0 Hz, 1H), 3.25 (ddd, J = 16.6, 14.5, 8.5 Hz, 1H), 2.81 (ddd, J
6
6 °C; TLC (SiO
2
) R
f
= 0.46 in 5:1 hexanes/acetone, p-anisaldehyde
) δ 7.16 (d, J = 7.5 Hz, 2H), 7.06 (d, J = 8
Hz, 2H), 2.44 (dd, J = 18.5, 8.5 Hz, 1H), 2.31 (s, 3H), 1.30 (dd, J = 7.5,
= 31.5, 16.5, 4.0 Hz, 1H), 2.60 (sept, J = 6.5 Hz, 1H), 1.12 (d, J = 6.5 Hz,
1
13
stain; H NMR (500 MHz, CDCl
3
3
3H), 1.08 (d, J = 6.5 Hz, 3H); C NMR (126 MHz, CDCl ) δ 210.5, 128.6,
125.5, 125.5, 100.1, 90.3 (d, J = 170.7 Hz), 47.6 (d, J = 26.3 Hz), 41.6,
1
3
19
5
.5 Hz, 1H), 1.03 (dd, J = 10.5, 6.0 Hz, 1H), 0.80 (s, 9H); C NMR (126
MHz, CDCl ) δ 135.5, 135.1, 129.5, 128.7, 66.4, 35.2, 31.7, 26.9, 21.1,
4.1; IR (neat) 3457, 2963, 2871, 1362, 1180, 1076, 907, 813, 550, 526
17.7, 17.7; F NMR (376 MHz, CDCl
3
) δ –174.9 (ddd, J = 46.4, 31.6,
3
13.9 Hz, 1F); IR (neat) 2966, 2926, 2852, 1713, 1467, 1379, 1070, 1021,
–
1
1
985, 758, 699 cm ; GC/MS (m/z): 194.1 (2%), 174.0 (3%), 151.0 (19%),
–
1
cm ; GC/MS (m/z): 204.1 (10%), 145.0 (41%), 119.1 (42%), 105.1
100%), 91.0 (15%), 57.1 (44%).
131.0 (46%), 109.0 (100%), 77.0 (20%); HRMS (m/z) calc'd for
+
(
C
12
H
15FONa [M + Na] : 217.1005, found 217.1001.
1
-Benzyl-2-(p-tolyl)cyclopropan-1-ol (1g): Clear colorless liquid; TLC
1-fluoro-4,4-dimethyl-1-phenylpentan-3-one (2c): The title compound was
1
19
(
(
(
SiO
500 MHz, CDCl
dd, J = 9.5, 7.0 Hz, 2H), 2.36 (s, 3H), 1.32–1.23 (m, 2H); C NMR (126
) δ 138.4, 135.7, 135.1, 129.5, 129.0, 128.5, 128.3, 126.6,
25.6, 61.0, 39.4, 30.0, 21.1, 18.0; IR (neat) 3395, 3027, 2924, 2364,
2
) R
f
= 0.39 in 5:1 hexanes/acetone, p-anisaldehyde stain; H NMR
prepared with
a
F
NMR yield of 59% containing 23% enone
(determined by H NMR) and was isolated as a white solid. Mp 37–
39 °C; TLC (SiO ) R = 0.54 in 5:1 hexanes/acetone, p-anisaldehyde
stain; H NMR (500 MHz, CDCl ) δ 7.42–7.31 (m, 5H), 6.02 (ddd, J =
46.5, 8.5, 4.5 Hz, 1H), 3.33 (ddd, J = 17.0, 14.0, 8.5 Hz, 1H), 2.77 (ddd, J
1
3
) δ 7.37–6.96 (m, 9H), 2.86 (d, J = 14.5 Hz, 1H), 2.46
1
3
2
f
1
MHz, CDCl
3
3
1
2
–
1
13
332, 1516, 1492, 1450, 1092, 813, 699, 530 cm ; GC/MS (m/z): 238.1
= 31.5, 17.0, 4.5 Hz, 1H), 1.13 (s, 9H); C NMR (126 MHz, CDCl
3
) δ
(
5%), 147.0 (20%), 119.0 (27%), 105.0 (100%), 91.0 (24%).
211.6, 128.6, 128.5, 125.5, 125.5, 90.5 (d, J = 170.4 Hz), 44.2 (d, J =
1
9
2
3
1
6.5 Hz), 26.3, 25.8; F NMR (376 MHz, CDCl
3
) δ –175.7 (ddd, J = 46.2,
1.6, 13.9 Hz, 1F); IR (neat) 2972, 2930, 1694, 1609, 1473, 1369, 1086,
1
-(tert-Butyl)-2-(4-(tert-butyl)phenyl)cyclopropan-1-ol (1h): White powder;
mp 72–74 °C; TLC (SiO 0.40 in 5:1 hexanes/acetone, p-
anisaldehyde stain; H NMR (500 MHz, CDCl ) δ 7.26 (d, J = 8.0 Hz, 2H),
–
1
028, 976, 855, 765, 699, 542 cm ; GC/MS (m/z): 208.1 (3%), 188.0
2
f
) R =
1
(
2%), 131.0 (100%), 103.0 (38%), 57.0 (46%); HRMS (m/z) calc'd for
3
+
13
C H17FONa [M + Na] : 231.1166, found 231.1161.
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201700899
FULL PAPER
3
-fluoro-1,3-diphenylpropan-1-one (2d): The title compound was
49–50 °C; TLC (SiO
2
) R
f
= 0.26 in 20:1 hexanes/acetone, p-anisaldehyde
1
9
1
prepared with a F NMR yield of 93%, and was isolated as a white solid.
Mp 63–65 °C; TLC (SiO 0.39 in 5:1 hexanes/acetone, p-
anisaldehyde stain; H NMR (500 MHz, CDCl ) δ 7.97 (d, J = 8.0 Hz, 2H),
.69–7.33 (m, 8H), 6.19 (ddd, J = 46.5, 8.0, 4.0 Hz, 1H), 3.81 (app. dt, J
3
stain; H NMR (500 MHz, CDCl ) δ 7.41 (d, J = 10.5 Hz, 2H), 7.30 (d, J =
2
)
R
f
=
9.5 Hz, 2H), 6.00 (ddd, J = 58.5, 11.0, 5.0 Hz, 1H), 3.36 (ddd, J = 21.1,
17.3, 11.0 Hz, 1H), 2.75 (ddd, J = 40.5, 21.5, 5.0 Hz, 1H), 1.32 (s, 9H),
1
3
1
3
7
=
1.14 (s, 9H); C NMR (126 MHz, CDCl
3
) δ 211.7, 151.6, 136.6, 136.5,
1
3
15.0, 8.5 Hz, 1H), 3.33 (ddd, J = 29.5, 17.0, 4.0 Hz, 1H); C NMR (126
) δ 196.1, 144.9, 139.6, 139.4, 136.7, 133.5, 132.8, 130.6,
29.0, 128.7, 128.7, 128.5, 128.5, 128.2, 125.7, 125.6, 122.1, 90.3 (d, J
125.5, 125.3, 125.3, 90.3 (d, J = 169.6 Hz),44.3, 44.0 (d, J = 27.0 Hz),
1
9
MHz, CDCl
3
3
34.6, 31.3, 25.9; F NMR (376 MHz, CDCl ) δ –174.0 (ddd, J = 46.4,
1
=
32.5, 13.8 Hz, 1F); IR (neat) 2960, 2928, 2905, 2868, 1704, 1476, 1364,
1
9
–1
171.2 Hz), 46.0 (d, J = 26.2 Hz); F NMR (376 MHz, CDCl
3
) δ –174.5
1082, 1002, 839, 582 cm ; GC/MS (m/z): 264.1 (4%), 249.1 (6%), 207.1
(
ddd, J = 46.0, 30.0, 14.9 Hz, 1F); IR (neat) 3063, 3030, 2937, 1685,
(6%), 187.1 (32%), 165.1 (31%), 131.0 (35%), 57.1 (100%); HRMS (m/z)
–
1
+
1
665, 1597, 1447, 1376, 1203, 995, 751, 687, 579, 547 cm ; GC/MS
calc'd for C17
H
25FONa [M + Na] : 287.1787, found 287.1785.
(
(
m/z): 228.1 (16%), 207.1 (48%), 131.0 (20%), 105.0 (100%), 77.1
+
78%); HRMS (m/z) calc'd for C15H13FONa [M + Na] : 251.0848, found
3
-fluoro-1,4-diphenylbutan-1-one (2i): The title compound was prepared
2
51.0482.
19
with a F NMR yield of 60%, and was isolated as an off-white solid. Mp
5–56 °C; TLC (SiO ) R = 0.43 in 5:1 hexanes/acetone, p-anisaldehyde
stain; H NMR (500 MHz, CDCl ) δ 7.91 (dd, J = 10.0, 1.0 Hz, 2H), 7.58
5
2
f
1
4
-fluoro-4-(p-tolyl)butan-2-one (2e): The title compound was prepared
3
1
9
with a F NMR yield of 47%, and was isolated as a pale yellow liquid.
(app. tt, J = 9.0, 1.6 Hz, 1H), 7.46 (app. t, J = 10.0 Hz, 2H), 7.36–7.29 (m,
2H), 7.26 (app. d, J = 8.5 Hz, 3H), 5.40 (app. doublet of quintets, J = 59.0,
7.0 Hz, 1H), 3.45 (ddd, J = 21.3, 19.0, 9.0 Hz, 1H), 3.18–3.04 (m, 3H);
1
TLC (SiO
2
) R
f
= 0.37 in 5:1 hexanes/acetone, p-anisaldehyde stain;
) δ 7.23 (d, J = 11.0 Hz, 2H), 7.19 (d, J = 8.5, 2H),
.91 (ddd, J = 47.0, 8.5, 4.5 Hz, 1H), 3.20 (ddd, J = 16.4, 14.8, 9.0 Hz,
H
NMR (500 MHz, CDCl
3
1
3
5
1
C NMR (126 MHz, CDCl
3
) δ 196.8, 136.8, 136.5, 133.4, 129.6, 128.7,
1
3
H), 2.81 (ddd, J = 32.0, 17.0, 4.0 Hz, 1H), 2.36 (s, 3H), 2.22 (s, 3H);
C
128.5, 128.1, 126.8, 90.4 (d, J = 171.7 Hz), 42.8 (d, J = 23.2 Hz), 41.2 (d,
1
9
NMR (126 MHz, CDCl
25.6, 90.1 (d, J = 170.4 Hz), 50.6 (d, J = 26.5 Hz), 30.9, 29.7; F NMR
376 MHz, CDCl ) δ –172.4 (ddd, J = 46.5, 31.9, 14.1 Hz, 1F); IR (neat)
959, 2923, 2855, 1720, 1668, 1609, 1457, 1366, 1258, 1180, 1044, 800
3
) δ 204.9, 143.5, 138.6, 138.6, 129.3, 125.6,
J = 21.0 Hz); F NMR (376 MHz, CDCl
3
) δ –179.0 (app. ddt, J = 47.2,
1
9
1
23.1, 16.5 Hz, 1F); IR (neat) 3031, 2959, 2930, 1682, 1597, 1447, 1379,
–
1
(
3
1213, 1083, 1009, 744, 686, 511 cm ; GC/MS (m/z): 222.1 (15%), 115.0
2
(18%), 105.0 (100%), 91.1 (9%), 77.0 (32%); HRMS (m/z) calc'd for
–
1
+
cm ; GC/MS (m/z): 180.1 (11%), 160.1 (15%), 145.0 (100%), 115.0
C
16
H
15FONa [M + Na] : 265.1005, found 265.1008.
+
(
42%), 91.0 (17%); HRMS (m/z) calc'd for C11H13FONa [M + Na] :
2
03.0848, found 203.0841.
4
-(4-ethylphenyl)-3-fluoro-1-phenylbutan-1-one (2j): The title compound
1
9
was prepared with a F NMR yield of 39%, and was isolated as a pale
yellow liquid (33.9 mg, 42%). TLC (SiO 0.44 in 5:1
hexanes/acetone, p-anisaldehyde stain; H NMR (500 MHz, CDCl ) δ
1
-fluoro-4,4-dimethyl-1-(p-tolyl)pentan-3-one (2f): The title compound
2
)
R
f
=
1
9
1
was prepared with a F NMR yield of 71%, and was isolated as a white
solid (36.7 mg, 55%). Mp 34–36 °C; TLC (SiO ) R = 0.22 in 20:1
hexanes/acetone, p-anisaldehyde stain; H NMR (500 MHz, CDCl ) δ
.25 (d, J = 7.0 Hz, 2H), 7.18 (d, J = 7.5 Hz, 2H), 5.98 (ddd, J = 46.5, 8.0,
.0 Hz, 1H), 3.33 (ddd, J = 22, 13.5, 8.5 Hz, 1H), 2.76 (ddd, J = 31.0,
3
2
f
7.94–7.88 (m, 2H), 7.59–7.53 (m, 1H), 7.47–7.43 (m, 2H), 7.20–7.13 (m,
4H), 5.39 (app. doublet of quintet, J = 47.0, 6.0 Hz, 1H), 3.44 (ddd, J =
16.8, 15.5, 7.0 Hz, 1H), 3.17–3.02 (m, 3H), 2.64 (q, J = 7.5 Hz, 2H), 1.24
1
3
7
4
1
1
3
3
(t, J = 7.5 Hz, 3H); C NMR (126 MHz, CDCl ) δ 196.9, 148.0, 142.8,
1
3
7.0, 4.0 Hz, 1H), 2.35 (s, 3H), 1.13 (s, 9H); C NMR (126 MHz, CDCl
3
)
137.9, 136.8, 134.9, 133.6, 133.5, 133.4, 133.2, 132.6, 29.5, 128.8,
δ 211.7, 142.9, 138.4, 136.7, 136.5, 129.6, 129.2, 128.3, 125.6, 125.5,
128.6, 128.5, 128.5, 128.2, 128.1, 128.0, 126.7, 90.5 (d, J = 171.7 Hz),
1
9
19
1
19.7, 90.5 (d, J = 169.6 Hz), 44.1 (d, J = 27.2 Hz), 26.4, 25.9, 21.2;
F
42.8 (d, J = 23.3 Hz), 40.8 (d, J = 21.2 Hz), 28.5, 15.6; F NMR (376
NMR (376 MHz, CDCl
3
) δ –173.8 (ddd, J = 46.1, 31.5, 13.6 Hz, 1F); IR
3
MHz, CDCl ) δ –178.7 (app. ddt, J = 47.7, 23.9, 15.8 Hz, 1F); IR (neat)
(
neat) 2966, 2926, 2871, 1708, 1604, 1369, 1080, 1002, 979, 817, 728,
2963, 2930, 2361, 2335, 1684, 1620, 1450, 1272, 1216, 1018, 983, 829,
–
1
–1
5
43 cm ; GC/MS (m/z): 222.1 (8%), 202.1 (6%), 145.1 (100%), 123.1
19FONa [M
754, 689 cm ; GC/MS (m/z): 250.1 (19%), 145.1 (12%), 117.1 (14%),
(
34%), 115.1 (22%), 91.1 (11%); HRMS (m/z) calc'd for C14
H
105.0 (100%), 91.1 (6%), 77.0 (29%); HRMS (m/z) calc'd for
+
+
+
Na] : 245.1318, found 245.1323.
C
18
H
19FONa [M + Na] : 293.1318, found 293.1323.
4
-fluoro-1-phenyl-4-(p-tolyl)butan-2-one (2g): The title compound was
1
9
prepared with a F NMR yield of 67%, and was isolated as an off-white
solid (36.3 mg, 47%). Mp 57–60 °C; TLC (SiO ) R = 0.41 in 5:1
hexanes/acetone, p-anisaldehyde stain; H NMR (500 MHz, CDCl ) δ
.34 (t, J = 7.5 Hz, 3H), 7.29 (d, J = 7 Hz, 2H), 7.24–7.15 (m, 4H), 5.92
ddd, J = 46.5, 8.5, 4.0 Hz, 1H), 3.75 (d, J = 5.0 Hz, 2H), 3.23 (ddd, J =
Acknowledgements
2
f
1
3
Funding was provided by the UIC Department of Chemistry and
the National Science Foundation (CAREER Award 1654490).
We thank Profs. Daesung Lee, Duncan Wardrop, Vladimir
Gevorgyan, Tom Driver, Laura Anderson, and Neal Mankad
7
(
1
3
1
1
5
6.3, 14.8, 9.0 Hz, 1H), 2.82 (ddd, J = 31.0, 16.5, 3.0 Hz, 1H), 2.36 (s,
1
3
3
H); C NMR (126 MHz, CDCl ) δ 204.4, 197.4, 143.5, 141.1, 138.6,
36.1, 136.0, 134.6, 133.4, 131.7, 129.7, 129.5, 129.3, 128.8, 128.8,
(
UIC) for helpful discussions and use of reagents and equipment.
28.4, 127.2, 127.1, 127.0, 125.7, 125.6, 124.3, 90.2 (d, J = 170.6 Hz),
1
9
3
1.0, 48.9 (d, J = 26.5 Hz), 48.3, 21.5, 21.2; F NMR (376 MHz, CDCl )
Keywords: cyclopropanols • fluorine • ketones • oxidation •
δ –172.5 (ddd, J = 46.2, 31.4, 13.9 Hz, 1F); IR (neat) 3027, 2963, 2920,
713, 1603, 1496, 1450, 1334, 1220, 1073, 1028, 817, 741, 696, 543
1
silver
–
1
cm ; GC/MS (m/z): 256.1 (3%), 165.0 (18%), 145.0 (13%), 123.1 (100%),
+
9
1.0 (22%); HRMS (m/z) calc'd for C17
H17FONa [M + Na] : 279.1161,
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9
compound was prepared with a F NMR yield of 90% containing 1%
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enone (determined by H NMR) and was isolated as a white solid. Mp
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Entry for the Table of Contents
FULL PAPER
Remote Fluorination
Yuanlin Deng, Nabeelah I. Kauser,
Shahidul M. Islam, and Justin T. Mohr*
Page No. – Page No.
Ag(II)-Mediated Synthesis of β-
Fluoroketones via Oxidative
Cyclopropanol Opening
A practical methodology for the synthesis of fluoroketones using commercially
2
available AgF and cyclopropanols is described. The regioselective introduction of
a remote C–F bond is enabled through a hypothetical oxidative radical mechanism.
This approach provides convenient access to valuable fluorinated ketone building
blocks.
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