Cis-selective preparation of 2,2-difluorocyclopropyl ketones via non-metal hydride reduction of 2,2-difluorocyclopropenyl ketones

Article abstract of DOI:10.1016/j.jfluchem.2013.02.003

Diastereoselective reduction of gem-difluorocyclopropenyl ketones was accomplished by their Br?nsted acid catalyzed reactions with the non-metal based hydride transfer reagent, Hantzsch ester (diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate) (H

Full text of DOI:10.1016/j.jfluchem.2013.02.003

Journal of Fluorine Chemistry 149 (2013) 119–124
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Cis-selective preparation of 2,2-difluorocyclopropyl ketones via non-metal
hydride reduction of 2,2-difluorocyclopropenyl ketones
*
Zhaoyun Zheng, William R. Dolbier Jr.
Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, United States
A R T I C L E I N F O
A B S T R A C T
Article history:
Diastereoselective reduction of gem-difluorocyclopropenyl ketones was accomplished by their Brønsted
acid catalyzed reactions with the non-metal based hydride transfer reagent, Hantzsch ester (diethyl 1,4-
dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate) (HEH). The high yield reactions produced a signifi-
cantly cis-enriched product mixture, from which the cis-isomer could be readily separated by column
chromatography.
Received 2 January 2013
Received in revised form 29 January 2013
Accepted 1 February 2013
Available online 11 February 2013
ß 2013 Published by Elsevier B.V.
Keywords:
Gem-difluorocyclopropenyl ketones
Cis-gem-difluorocyclopropyl ketones
Hantzsch ester
Stereoselective synthesis
1. Introduction
conditions (Scheme 2) [9]. Therefore an acid-catalyzed process was
sought. Encouragingly 2,2-difluorocyclopropyl ketones were found
Gem-difluorocyclopropanes remain compounds of continued
interest as witnessed by the significant number of papers
published in recent years that have been devoted to methods
for their synthesis [1–6]. All of these methods involve the
generation of difluorocarbene, followed by the addition of this
somewhat reluctant reactive intermediate to alkenes.
to retain both fluorines during an acid catalyzed ring opening
process (Scheme 3) [10].
Based on these results, there is a good reason to believe that
under acidic conditions, and with the appropriate reducing agent,
one might be able to reduce the double bond without destroying
the cyclopropane ring. Upon examination of the literature, it was
determined that Hansch ester (diethyl 1,4-dihydro-2,6-dimethyl-
3,5-pyridinedicarboxylate) (HEH) might be a good candidate for
accomplishing this task. Hantzsch ester is not only simply prepared
[11], but it has also been widely used as a hydride transfer reagent,
usually under mild conditions, with Brønsted acid catalysis (i.e.,
Scheme 4) [12].
Among these methods, only the first and the last methods [1,6]
provide useful yields in reaction with
a,b-unsaturated carbonyl
compounds. In particular, TFDA (trimethylsilyl 2-(fluorosulfonyl)-
2,2-difluoroacetate) has become recognized as the reagent of
choice in reactions with electron-deficient substrates, such as
unsaturated ketones and esters. However, even with TFDA, the use
of -substituted -unsaturated ketones as substrates has
a,b-
b
a,b
remained a challenge. Because of this, an alternative approach
that used acetals as substrates was designed (Scheme 1) [7]. In
addition to the complication of added steps, this procedure yielded
only limited success.
Because TFDA was reported to have no problem in its reactions
with conjugated acetylenic ketones (Scheme 2) [8], a method was
sought for reduction of these 3,3-difluorocyclopropenyl ketone
products to their cyclopropane analogs. These 3,3-difluorocyclo-
propenyl ketones had been found to undergo defluorinative, ring-
opening processes in their reactions with nucleophiles under basic
2. Results
In a preliminary reaction designed to test the feasibility of the
reaction, p-toluenesulfonic acid was chosen as the acid catalyst
with 10% loading. This initial reaction provided 60% conversion by
simply mixing the substrate with 2 equivalents of HEH in CH3CN at
room temperature overnight. TLC could be used to follow
consumption of the HEH. Other than the remaining starting
material and the products, no other detectable compounds were
observed in
a
19F NMR spectrum of the reaction mixture.
Interestingly, the cis-isomer, which is believed to be thermody-
namically less stable than the trans-isomer, was the dominant
product, with a cis/trans ratio 67:33 being observed. A number of
other common Brønsted acids were examined, and they all favored
* Corresponding author. Tel.: +1 352 392 0591.
E-mail address: wrd@chem.ufl.edu (W.R. Dolbier Jr.).
0022-1139/$ – see front matter ß 2013 Published by Elsevier B.V.
http://dx.doi.org/10.1016/j.jfluchem.2013.02.003

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Scheme 1. Acetal method for preparation of difluorocyclopropyl ketones.
Scheme 2. The preparation of difluorocyclopropene and its properties.
Scheme 3. Ring opening reaction of difluorocyclopropane ketone by HBr in ionic liquid.
Scheme 4. The application of HEH as a hydride transfer reagent.
the cis product, giving similar conversions and selectivities. Using
pivalic acid (D) as catalyst, solvent effects on the reaction were
evaluated. THF led to a messy reaction mixture, whereas non-polar
solvents, such as toluene and dichloromethane, slowed down the
reaction, but gave better selectivity. Dichloromethane provided
the best combined result regarding conversion and selectivity
(entry 8). Lowering the temperature to 0 8C did not appear to have
a significant effect upon the selectivity. Although 10% of catalyst
appears to be the optimal choice, when using only 2% of the
catalyst, a good conversion was still obtained (entry 9) (Table 1).
With the hope of increasing the selectivity of the reaction, a
number of more sterically demanding benzoic acids were
examined. By examining Table 2, it can be seen that acids E, F
and G yielded similar selectivity, with a cis/trans ratio about 80/20,
which is better than that obtained by use of catalyst D. It is
puzzling that the apparently most bulky acid H provided inferior
results (entry 4). Sterically demanding phenol I also catalyzed the
reaction and gave stereochemical results comparable to those of
the bulky acids. Further solvent optimization using catalyst E,
which gave the best conversion, indicated that toluene gave the
highest cis/trans ratio 85/15 although the reactions proceeded
slower as reflected by the low conversion after 20 h (entry 7).
To explore the limitations of the reaction, a number of
cyclopropenyl ketone substrates were prepared and examined
under the optimized conditions of entry 7. Because of the relatively
slow reaction rate under these conditions, 20 mole % of catalyst
was used, which resulted in over 97% conversion for all substrates
in 4 days.
The results as given in Scheme 5 indicate that the reaction has
excellent substrate scope. Regardless of whether they were
electron-deficient or electron-rich, all substrates gave almost
quantitative NMR yields for the combined cis- and trans-products.
Importantly, the cis- and trans-isomers were generally able to be
separated by column chromatography to obtain the major cis
compound as a pure product, with the less polar trans-isomer
eluting first. The yields reported in Scheme 5 are for the isolated,
major cis-isomer.
3. Discussion
The proposed mechanism for the catalytic cycle is given in
Scheme 6. The ketone is first activated by Brønsted acid, followed
by attack by HEH to form enol 4. Enol 4, which should be stable to
elimination of fluoride under the acidic conditions, then tauto-
merizes to product ketone 2 by diastereoselective protonation by
the Brønsted acid, as depicted in Fig. 1.
To demonstrate kinetic control for the reaction, a control
reaction was conducted wherein pure cis-product, 2a, was
subjected to the usual reaction conditions, to see if isomerization
would occur. However, no trans isomer was able to be detected by
19F NMR after 24 h (Scheme 7), thus indicating that kinetic control
was operating. Based upon our understanding of the overall
process, we considered it to be reasonable that more sterically
demanding substrates or Brønsted acids might provide higher
diastereoselectivity in the reaction. However, neither assumption
proved correct, with no informative trends in diastereoselectivity

Z. Zheng, W.R. Dolbier Jr. / Journal of Fluorine Chemistry 149 (2013) 119–124
121
Table 1
Screening of conditions for the reduction of difluorocyclopropenes.
Entry
Catalyst
Amount
Solvent
Conversion (%)a
Cis:transa
1
2
3
4
5
6
7
8
9
A
B
C
10%
10%
10%
10%
10%
10%
10%
10%
2%
CH3CN
CH3CN
CH3CN
CH3CN
THF
60
45
67:33
61:39
56:44
62:38
–
54
D
D
D
D
D
D
50
100
54
Toluene
MTBE
DCM
73:27
74:26
73:27
73:27
30
90
DCM
65
a
Determined by 19F NMR.
Scheme 5. The reaction of difluorocyclopropene with HEH catalyzed by Brønsted acid.

122
Z. Zheng, W.R. Dolbier Jr. / Journal of Fluorine Chemistry 149 (2013) 119–124
Table 2
Testing sterically demanding Brønsted acids.a
Entry
Catalyst
Amount
Solvent
Conversion (%)
Cis:trans
1
2
3
4
5
6
7
8
E
F
G
H
I
10%
10%
10%
10%
10%
10%
10%
10%
DCM
78
64
72
71
64
71
48
23
80:20
79:21
78:22
59:41
74:26
76:24
85:15
82:18
DCM
DCM
DCM
DCM
E
E
E
ClCH2CH2Cl
Toluene
MTBE
a
At RT for 20 h.
Scheme 6. Proposed mechanism for the catalytic reduction of difluorocyclopropene.
Scheme 7. Control reaction for the cis-gem-difluorocyclopropyl ketone.
Fig. 1. Diastereoselective protonation of enol 4.

Z. Zheng, W.R. Dolbier Jr. / Journal of Fluorine Chemistry 149 (2013) 119–124
123
being exhibited by steric modifications of either the substrates or
the acids, as seen in Table 2 and Scheme 5.
5.2.6. Phenyl 2,2-difluoro-3-(4-t-butylphenyl)cyclopropenyl ketone
(1f)
(86%); 1H NMR: 1.37 (s, 9H), 7.59 (m, 4H), 7.69 (m, 1H), 7.96 (m,
2H), 8.16 (m, 2H); 19F NMR
À104.3 (s, 2F).
d
4. Conclusions
5.2.7. Phenyl 2,2-difluoro-3-(4-bromophenyl)cyclopropenyl ketone
An efficient procedure for cis-selective reduction of gem-
difluorocyclopropenyl ketones has been reported in this paper.
The process, using Hantzsch ester as the hydride transfer reagent,
under Brønsted acid catalysis, comprises a general, high yield
procedure for preparing cis-preferred substituted gem-difluorocy-
clopropyl ketones. Based upon reported enantioselective reduc-
tions using HEH [12], it may be possible to elaborate on this study
to provide a process that is both diastereoselective and enantio-
selective for the preparation of cis-gem-difluorocyclopropyl
ketones.
(1g) [8]
(85%); 1H NMR
d
d
7.60 (m, 2H), 7.72 (m, 3H), 7.89 (m, 2H), 8.14
À104.1 (s, 2F).
(m, 2H); 19F NMR
5.2.8. Methyl 2,2-difluoro-3-phenylcyclopropenyl ketone (1h)
(75%); 1H NMR 2.59 (s, 3H), 7.56 (m, 3H), 7.86 (m, 2H); 19F
NMR
À107.7 (s, 2F).
d
d
5.2.9. 4-t-butylphenyl 2,2-difluoro-3-phenylcyclopropenyl ketone
(1i)
(90%); 1H NMR
À104.2 (s, 2F).
d 1.38 (s, 9H), 7.60 (m, 5H), 7.96 (m, 2H), 8.12 (m,
2H); 19F NMR
d
5. Experimental
5.2.10. Phenyl 2,2-difluoro-3-pentylcyclopropenyl ketone (1j) [8]
(55%); 1H NMR
0.91 (t, J = 9.0 Hz, 3H), 1.38 (m, 4H), 1.77 (m,
2H), 2.74 (m, 2H), 7.55 (t, J = 9.0 Hz, 2H), 7.67 (m, 1H), 8.04 (m, 2H);
19F NMR
À102.2 (s, 2F).
5.1. General experimental procedures
d
NMR spectra were obtained in CDCl3 using TMS and CFCl3 as the
d
internal standards for 1H/13
C
NMR and 19F NMR spectra,
respectively. Substituted propynones [13] and TFDA [14] were
prepared according to the previous literature, all other chemicals
were purchased from Aldrich, Alfa, or Fisher without further
purification.
5.3. Typical procedure for reduction of gem-difluorocyclopropenyl
ketones with HEH
Brønsted acid, 3,5-di-t-butylbenzoic acid, (18.3 mg, 20 mol%)
was added to a mixture of phenyl 2,2-difluoro-3-phenylcyclopro-
penyl ketone (1a) (100 mg, 0.39 mmol), Hantzsch ester (diethyl
5.2. General procedure for preparation of gem-difluorocyclopropenyl
ketones
1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate)
(HEH)
(0.20 g, 2 equiv.), toluene (1 mL) in a 10 mL round bottomed flask
at room temperature, and the solution was stirred until the ketone
was consumed (as monitored by TLC or 19F NMR). In order to attain
97% conversion, about 4 days was required. The mixture, which
was an almost pure mixture of cis and trans isomers, was purified
by column chromatograph to provide the pure cis-isomer. Scheme
5 gives the cis:trans ratios. Yields given below are for the pure cis-
isomer.
The procedure followed was essentially that of Cheng and Chen
[8].
A mixture of substituted propynone (3.55 mmol), NaF
(10 mol%), diglyme (2 mL) was heated to 120 8C under a blanket
of N2. TFDA (5.3 mmol) was then added dropwise (about 40 min),
with stirring at this temperature for a total of 1 h. The solution was
then cooled to room temperature, and subjected directly for
purification by column chromatography (silica gel, using hexane/
dichloromethane).
5.3.1. Phenyl 2,2-difluoro-3-phenylcyclopropyl ketone (cis-isomer)
5.2.1. Phenyl 2,2-difluoro-3-phenylcyclopropenyl ketone (1a)
(85%); spectroscopic data consistent with those published in
the literature [8].
(2a)
(79%); 1H NMR
d
3.47 (td, J = 11.3 and 2.8 Hz, 1H), 3.69 (td,
J = 12.4 and 1.8 Hz, 1H), 7.29 (s, 5H), 7.42–7.53 (m, 2H), 7.54–7.71
(m, 1H), 7.89–8.05 (m, 2H); 13C NMR
33.19 (dd, J = 8.2 and
8.2 Hz), 34.59 (dd, J = 9.0 and 9.0 Hz), 113.04 (dd, J = 284.2 and
284.2 Hz), 127.9, 128.3, 128.6, 128.9, 129.8, 133.7, 138.0, 190.3; 19
d
5.2.2. Phenyl 2,2-difluoro-3-(4-methylphenyl)cyclopropenyl ketone
(1b) [8]
F
(87%); 1H NMR
d
2.46 (s, 3H), 7.37 (d, J = 6.0 Hz, 2H), 7.59 (m,
NMR
d
À115.7 (dt, J = 155 and 14 Hz, 1F), À147.4 (d, J = 155 Hz, 1F);
2H), 7.69 (m, 1H), 7.92 (d, J = 6.0 Hz, 2H), 8.16 (m, 2H); 19F NMR
À104.3 (s, 2F).
d
HRMS: calcd for C16H12F2O [M+Na]+, 281.0748; found, 281.0759.
5.3.2. Phenyl 2,2-difluoro-3-phenylcyclopropyl ketone (trans-isomer)
5.2.3. Phenyl 2,2-difluoro-3-(3-methylphenyl)cyclopropenyl ketone
3a
(1c)
1H NMR
d
3.62–3.69 (m, 1H), 3.83–3.91 (m, 1H), 7.34 (m, 5H),
7.54 (m, 2H), 7.65 (m, 1H), 8.05 (m, 2H); 13C NMR
32.7 (m), 36.9
(m), 111.9 (m), 128.1, 128.5, 128.7, 128.9, 129.1, 132.1, 134.1,
137.2, 190.4; 19F NMR
[M+Na]+, 281.0748; found, 281.0759.
(89%); 1H NMR
d
2.46 (s, 3H), 7.43 (m, 2H), 7.60 (m, 2H), 7.70 (m,
d
1H), 7.84 (m, 2H), 8.16 (m, 2H); 19F NMR
d
À104.3 (s, 2F).
d
À132.55 (m); HRMS: calcd for C16H12F2O
5.2.4. Phenyl 2,2-difluoro-3-(3,5-dimethylphenyl)cyclopropenyl
ketone (1d)
(91%); 1H NMR
d
2.41 (s, 6H), 7.25 (s, 1H), 7.65 (m, 5H), 8.16 (m,
5.3.3. Phenyl 2,2-difluoro-3-(4-methylphenyl)cyclopropyl ketone
2H); 19F NMR
d
À104.4 (s, 2F).
(2b)
(72%); 1H NMR
d
2.27 (s, 3H), 3.42 (m, 1H), 3.64(m, 1H), 7.14 (dd,
J = 18.0 and 9.0 Hz, 4H), 7.44 (m, 2H), 7.55 (m, 1H), 7.89 (m, 2H);
13C NMR
21.43, 33.22 (dd, J = 8.2 and 8.2 Hz), 34.52 (dd, J = 9.7
and 9.7 Hz), 113.12 (dd, J = 284.2 and 284.2 Hz), 126.5, 128.3,
128.9, 129.3, 129.6, 133.6, 137.7, 138.1, 190.4; 19F NMR
À115.6
5.2.5. Phenyl 2,2-difluoro-3-(3,5-di-t-butylphenyl)cyclopropenyl
ketone (1e)
d
(88%); 1H NMR
d
1.39 (s, 18H), 7.59 (m, 2H), 7.70 (m, 2H), 7.88
(m, 2H), 8.17 (m, 2H); 19F NMR
d
À104.1 (s, 2F).
d

124
Z. Zheng, W.R. Dolbier Jr. / Journal of Fluorine Chemistry 149 (2013) 119–124
(dt, J = 155 and 14 Hz, 1F), À147.4 (d, J = 156 Hz, 1F); HRMS: calcd
NMR
112.7 (dd, J = 285.0 and 285.0 Hz), 122.2, 128.3, 128.8, 129.0, 131.5,
131.7, 133.9, 137.9, 190.0; 19F NMR
1F), À147.5 (d, J = 155 Hz, 1F); HRMS: calcd for C16H11BrF2O
[M+Na]+, 358.9854; found, 358.9855; Anal. Calcd for C16H11BrF2O:
C, 57.00; H, 3.29. Found: 57.31; H, 3.29.
d 33.14 (dd, J = 9.0 and 9.0 Hz), 33.7 (dd, J = 9.0 and 9.0 Hz),
for C17H14F2O [M+Na]+, 295.0905; found, 295.0913.
d
À116.1(dt, J = 155 and 14 Hz,
5.3.4. Phenyl 2,2-difluoro-3-(3-methylphenyl)cyclopropyl ketone
(2c)
(70%); 1H NMR
d
2.30 (s, 3H), 3.42 (t, J = 15.0 Hz, 1H), 3.66 (t,
J = 12.0 Hz, 1H), 7.08 (m, 4H), 7.47 (t, J = 6.0 Hz, 2H), 7.58 (m, 1H),
7.92 (m, 2H); 13C NMR
21.63, 33.21 (dd, J = 8.2 and 8.2 Hz), 34.57
d
5.3.9. Methyl 2,2-difluoro-3-phenylcyclopropyl ketone (2h)
(dd, J = 9.0 and 9.0 Hz), 113.10 (dd, J = 285.0 and 285.0 Hz), 126.8,
128.3, 128.4, 128.8, 128.9, 129.6, 130.5, 133.6, 138.2, 190.4; 19F
(61%); 1H NMR
d
1.92(s, 3H), 2.97 (t, J = 15 Hz, 1H), 3.33 (td,
J = 12 Hz, 1H), 7.32 (s, 5H); 13C NMR
31.2, 33.8 (dd, J = 9.0 and
9.0 Hz), 33.08 (dd, J = 10.5 and 10.5 Hz), 112.4 (t, J = 287.3 Hz),
128.3, 128.9, 129.6, 129.8, 199.3; 19F NMR
d
NMR
d
À115.7 (dt, J = 155 and 11 Hz, 1F), À147.4 (d, J = 155 Hz, 1F);
HRMS: calcd for C17H14F2O [M+Na]+, 295.0905; found, 295.0918.
Anal. Calcd for C17H14F2O: C, 74.99; H, 5.18. Found: C, 74.94; H,
5.57.
d
À116.6 (d, J = 160 Hz,
1F), À144.9 (d, J = 164 Hz, 1F); HRMS: calcd for C11H10F2O [M+Na]+,
219.0592; found, 219.0599; Anal. Calcd for C11H10F2O: C, 67.34; H,
5.14. Found: C, 67.06; H, 5.46.
5.3.5. Phenyl 2,2-difluoro-3-(3,5-dimethylphenyl)cyclopropyl ketone
(2d)
5.3.10. 4-t-butylphenyl 2,2-difluoro-3-phenylcyclopropyl ketone (2i)
(69%); 1H NMR
d
2.26 (s, 6H), 3.40 (t, J = 12.0 Hz, 1H), 3.65(t,
J = 12.3 Hz, 1H), 6.89 (s, 3H), 7.48 (m, 2H), 7.59 (m, 1H), 7.95 (d,
J = 8.0 Hz, 2H); 13C NMR
21.51, 33.12 (dd, J = 9.0 and 9.0 Hz),
34.57 (dd, J = 9.0 and 9.0 Hz), 113.10 (dd, J = 284.3 and 284.3 Hz),
127.5, 128.3, 128.9, 129.4, 129.7, 133.5, 137.9, 138.2, 190.3; 19F
(80%); 1H NMR
d
1.35 (s, 9H), 3.44 (t, J = 12 Hz, 1H), 3.66 (t,
J = 15 Hz, 1H), 7.29 (s, 5H), 7.50 (d, J = 9 Hz, 2H), 7.86 (m, J = 9 Hz,
2H); 13C NMR
31.3, 33.09 (t, J = 8.2 Hz), 34.43 (t, J = 9.0 Hz), 35.4,
113.0 (t, J = 285.7 Hz), 125.9, 127.9, 128.3, 128.5, 129.8, 135.6,
157.5, 189.9; 19F NMR
d
d
d
À115.9 (dt, J = 155 and 14 Hz, 1F), À147.4
NMR
d
À115.6 (dt, J = 155 and 14 Hz, 1F), À147.4 (d, J = 156 Hz, 1F);
(d, J = 156 Hz, 1F); HRMS: calcd for C20H20F2O [M+Na]+, 337.1374;
found, 337.1388; Anal. Calcd for C20H20F2O: C, 76.41; H, 6.41.
Found: C, 76.17; H, 6.61.
HRMS: calcd for C18H16F2O [M+Na]+, 309.1061; found, 309.1072.
5.3.6. Phenyl 2,2-difluoro-3-(3,5-di-t-butylphenyl)cyclopropyl
ketone (2e)
5.3.11. Phenyl 2,2-difluoro-3-pentylcyclopropyl ketone (2j/3j) (cis/
trans-mixture)
(68%); 1H NMR
d
1.20 (s, 18H), 3.45 (td, J = 12.0 and 3.0 Hz, 1H),
3.65 (td, J = 12.0 and 3.0 Hz, 1H), 7.01 (s, 2H), 7.25 (m, 1H), 7.46 (m,
2H), 7.57 (m, 1H), 7.93 (m, 2H); 13C NMR
31.5, 32.85 (dd, J = 8.3
and 8.3 Hz), 34.9, 35.2 (dd, J = 9.7 and 9.7 Hz), 113.10 (dd, J = 284.3
and 284.3 Hz), 121.8, 124.1, 128.4, 128.6, 128.9, 133.6, 138.1,
150.8, 190.4; 19F NMR
(d, J = 156 Hz, 1F); HRMS: calcd for C24H28F2O [M+Na]+, 393.2000;
found, 393.2009; Anal. Calcd for C24H28F2O: C, 77.81; H, 7.62.
Found: C, 77.51; H, 8.09.
(95%). 1H NMR
d
0.89 (m), 1.26–1.84 (m), 2.16 (m), 2.62 (m),
d
3.01 (m), 3.23 (m), 7.50 (m), 7.59 (m), 7.97 (m); 19F NMR
d
À115.9
(dt, J = 152 and 14 Hz), À134.7 (m), À147.4 (d, J = 152 Hz).
d
À115.7 (dt, J = 155 and 11 Hz, 1F), À147.9
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5.3.7. Phenyl 2,2-difluoro-3-(4-t-butylphenyl)cyclopropyl ketone (2f)
(81%); 1H NMR
d
1.26 (s, 9H), 3.41 (td, J = 12.0 and 3.0 Hz, 1H),
3.62 (td, J = 12.0 and 3.0 Hz, 1H), 7.21 (dd, J = 8.0 and 9.0 Hz, 4H),
7.44(m, 2H), 7.55 (m, 1H), 7.90 (m, 2H); 13C NMR
31.5, 32.85(dd,
d
J = 8.3 and 8.3 Hz), 34.5 (dd, J = 9.7 and 9.7 Hz), 34.7, 113.10 (dd,
J = 285.0 and 285.0 Hz), 125.5, 126.5, 128.3, 128.9, 129.5, 133.6,
138.2, 150.8, 190.5; 19F NMR
d
À115.8 (dt, J = 155 and 11 Hz, 1F),
[7] W. Xu, Q.-Y. Chen, Org. Biomol. Chem. 1 (2003) 1151–1156.
[8] Z.-L. Cheng, Q.-Y. Chen, Synlett (2006) 478–480.
À147.5 (d, J = 154 Hz, 1F); HRMS: calcd for C20H20F2O [M+Na]+,
[9] Z.-L. Cheng, Q.-Y. Chen, J. Fluorine Chem. 127 (2006) 894–900.
[10] W. Xu, W.R. Dolbier, J. Salazar Jr., J. Org. Chem. 73 (2008) 3535–3538.
[11] G. Barbe, A.B. Charette, J. Am. Chem. Soc. 130 (2008) 18–19.
[12] N.J.A. Martin, B. List, J. Am. Chem. Soc. 128 (2006) 13368–13369.
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Commun. (2005) 1037–1039.
337.1374; found, 337.1382.
5.3.8. Phenyl 2,2-difluoro-3-(4-bromophenyl)cyclopropyl ketone (2g)
(75%); 1H NMR
d
3.37 (td, J = 12.0 and 3.0 Hz, 1H), 3.68 (td,
J = 15.0 and 3.0 Hz, 1H), 7.17 (m, 4H), 7.42(m, 5H), 7.92 (m, 2H); 13
C
[14] W.R. Dolbier, J.-X. Duan Jr., F. Tian, Q.-Y. Chen, Org. Synth. 80 (2003) 172–176.